USRE44302E1 - N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use - Google Patents

N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use Download PDF

Info

Publication number
USRE44302E1
USRE44302E1 US12/722,170 US72217010A USRE44302E US RE44302 E1 USRE44302 E1 US RE44302E1 US 72217010 A US72217010 A US 72217010A US RE44302 E USRE44302 E US RE44302E
Authority
US
United States
Prior art keywords
acetyl
acid
agents
skin
group
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US12/722,170
Inventor
Ruey J. Yu
Eugene J. Van Scott
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22852222&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=USRE44302(E1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Priority to US12/722,170 priority Critical patent/USRE44302E1/en
Priority to US13/046,047 priority patent/USRE44017E1/en
Application granted granted Critical
Publication of USRE44302E1 publication Critical patent/USRE44302E1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/401Proline; Derivatives thereof, e.g. captopril
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • A61K31/4045Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • A61K31/405Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7008Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A61K8/447Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof containing sulfur
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/04Antipruritics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/10Anti-acne agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/007Preparations for dry skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q3/00Manicure or pedicure preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/006Antidandruff preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/008Preparations for oily skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/02Preparations for cleaning the hair

Definitions

  • This application relates to topical compositions containing N-acetyl-aldosamines, N-acetylamino acids, and related N-acetyl compounds, and their use in alleviating or improving various cosmetic conditions and dermatological disorders including signs of aging, changes or damage to skin, nail and hair associated with intrinsic aging and/or extrinsic aging, as well as changes or damage caused by extrinsic factors such as sunlight, radiation, air pollution, wind, cold, heat, dampness, chemicals, smoke, and cigarette smoking; and for certain skin disorders associated with or due to itching and/or inflammation.
  • topical compositions comprising from 0.01% to 50% of N-acetylcysteine or a derivative of N-acetylcysteine, from 0.01% to 0.5% of an odor masking material, and a topical carrier are disclosed to improve the appearance of skin.
  • N-Acetylcysteine is N-acetylated cysteine which is a thiol containing amino acid, also called ⁇ -acetamido- ⁇ -mercaptopropanoic acid.
  • Topical compositions containing N-acetylcysteine have been claimed to improve physical appearance of the skin including cosmetic wrinkles.
  • N-acetylcysteine contains a free thiol group, thus, is known as an antioxidant.
  • the affect of N-acetylcysteine is claimed to be due to its antioxidant property.
  • N-Acetylcysteine, as an antioxidant substance also has been indicated as protective against pulmonary oxygen toxicity (Eur. Respir. J. 2, 116-126, 1989).
  • N-acetylcysteine is also associated with a number of significant drawbacks.
  • N-acetylcysteine is known to degrade under ordinary storage conditions and result in a malodorous smell. The malodor is suggested to be caused by the release of thiol compounds and hydrogen sulfide upon degradation.
  • topical compositions containing N-acetylcysteine have little or no commercial use due to the strong malodor of N-acetylcysteine.
  • PCT/US96/16534 claimed that the malodor could be masked by addition of certain perfume chemicals at concentrations ranging from 0.01 to 0.5% by weight.
  • the perfume chemicals include aromatic esters, aliphatic esters, aromatic alcohol, aliphatic alcohols, aliphatic ketones, aromatic aldehydes, aliphatic aldehydes, aromatic ethers and aliphatic ethers. Because the malodorous thiol compounds and hydrogen sulfide have not been chemically neutralized or destroyed, however, the transient masking effect is not a satisfactory solution for most consumers, and therefore is not a viable approach for commercialization of N-acetylcysteine in cosmetic industry.
  • N-aldosamines, N-acetylated amino acids and related compounds are topically effective for various cosmetic conditions and dermatological indications including the signs of skin, nail and hair changes associated with intrinsic and/or extrinsic aging.
  • the N-acetylated amino acids and related compounds do not necessarily contain thiol groups and are not necessarily antioxidants.
  • N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds have unexpected properties.
  • Topical applications of compositions comprising N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds have been found to improve cosmetic conditions and dermatological disorders including cosmetic as well as clinical signs of changes in skin, nails and hair associated with intrinsic and/or extrinsic aging, or the damages caused by extrinsic factors such as sunlight, radiation, air pollution, wind, cold, dampness, heat, chemicals, smoke, and cigarette smoking.
  • the signs of skin changes associated with intrinsic and/or extrinsic aging and the skin damages caused by extrinsic factors include thinning of skin; fragile skin; deepening of skin lines and fine lines; wrinkles, including fine and course wrinkles; blemishes; atrophy; pigmented spots, blotches and mottles, nodules and mottled skin; pre-cancerous lesions; elastotic changes characterized by leathery, lusterless, uneven, coarse, rough, dry and/or yellowish skin; loss of skin elasticity and recoilability; loss of skin lubricating substances; changes in qualities and quantities of glycosaminoglycans and proteoglycans and collagen and elastic fibers; solar elastosis; decrease in collagen fibers; diminution in the number and diameter of elasitic fibers in the papillary dermis; atrophy; stretch marks; reduction in subcutaneous adipose tissue; deposition of abnormal elastic materials in the dermis leading to thickening of the derm
  • the signs of nails and hair changes associated with intrinsic aging and the damages caused by extrinsic factors include thinning, fragility, splitting, lack of luster, uneven surface, and loss of flexibility and elasticity.
  • compositions comprising at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids and related compounds, present in a therapeutically effective amount and in a pharmaceutically acceptable vehicle for topical treatment of cosmetic conditions or dermatological disorders.
  • the composition further comprises a cosmetic, pharmaceutical, or other topical agent.
  • a method for treating cosmetic conditions and dermatological disorders comprising topically applying a therapeutically effective amount of a composition comprising at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids and related compounds, in a pharmaceutically acceptable vehicle.
  • the method comprises topically applying a therapeutically effective amount of a composition comprising at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids and related compounds, and at least one cosmetic, pharmaceutical, or other topical agent, in a pharmaceutically acceptable vehicle.
  • N-Acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds which are useful for topical treatment of skin, nail and hair changes associated with intrinsic and/or extrinsic aging and extrinsic factors include, inter alia, N-acetyl-aldosamines which are derivatives of aminosugars and include N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-glucosamine, N-acetyl-galactosamine and N-acetyl-mannosamine, and N-acetylamino acids which are N-acetyl derivatives of amino acids and include N-acetyl-glycine, N-acetyl-proline, N-acetyl-lysine, N-acetyl-arginine and N-acetyl-tryptophan.
  • N-acetyl-aldosamines are N-acetylated aminosugars in which the acetylamino group is preferably located at position 2 of the carbon chain.
  • the generic structure or formula of N-acetyl-aldosamines which are topically beneficial for various cosmetic and dermatologic indications may be represented as follows:
  • n is an integer, preferably 1-19;
  • R 1 is selected from the group consisting of CHO, CONH 2 , and COOR 3 ;
  • R 2 is selected from the group consisting of H, l, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated, isomeric or non-isomeric, straight or branched chain or cyclic form, having 1 to 19 carbon atoms; and
  • R 3 is selected from the group consisting of H, an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms.
  • N-Acetyl-aldosamines may be present as saturated or unsaturated, isomeric or non-isomeric, straight or branched chain or cyclic form.
  • a typical cyclic form of an N-acetyl-aldosamine is a five member ring (furanose form) or a six member ring (pyranose form).
  • N-acetyl-aldosamines and related compounds N-acetyl-glycerosamine, N-acetyl-erythrosamine, N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine, N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine, N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine, N-acetyl-talosamine, N-acetyl-glucoheptosamine, N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine, N-acetyllacto
  • amides and esters of the foregoing acid compounds also are contemplated by the present invention.
  • Examples of five and six member ring forms are 2-acetamido-2-deoxy-D-ribofuranoside, 2-acetamido-2-deoxy-D-ribopyranoside, 2-acetamido-2-deoxy-D-glucofuranoside, 2-acetamido-2-deoxy-D-glucopyranoside, 2-acetamido-2-deoxy-D-galactofuranoside and 2-acetamido-2-deoxy-D-galactopyranoside.
  • N-acetylamino acids are N-acetyl derivatives of amino acids.
  • generic structure or formula of N-acetylamino acids and related compounds which are topically beneficial for various cosmetic and dermatologic indications may be represented as follows:
  • R 1 is H, or an alkyl or aralkyl group having 1 to 14 carbon atoms; n is an integer, preferably from 0 to 5; R 2 is OH, NH 2 or OR 3 ; and R 3 is an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms; the alkyl, aralkyl or aryl group may be saturated or unsaturated, isomeric or non-isomeric, straight or branched chain or cyclic form; and in addition R 1 may carry OH, SH, SCH 3 , COOH, NH 2 CONH 2 , guanidine or heterocyclic group; the H attached to a carbon atom may be substituted by I, F, Cl, Br or alkoxyl group having 1 to 9 carbons.
  • N-Acetylamino acids may be present as isomeric or non-isomeric, as a free acid, salt, lactone, amide or ester form.
  • N-acetylamino acids and related compounds N-acetyl-glycine, N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl-serine, N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-cysteine, N-acetyl-methionine, N-acetyl-aspartic acid, N-acetyl-asparagine, N-acetyl-glutamic acid, N-acetyl-glutamine, N-acetyl-arginine, N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine, N-acetyl-tryptophan, N-acet
  • N-acetylamino acids and related N-acetyl compounds may be present as a free acid, salt, lactone, amide or ester form.
  • these compounds include N-acetyl-cysteine ammonium salt, N-acetyl-homocysteine thiolactone, N-acetyl-L-cystine methyl ester, N-acetyl-L-tryosinamide, N-acetyl-L-tryosine ethyl ester, N-acetyl-serine amide, N-acetylglycine methyl ester, N-acetylglycinamide, and N-acetyl-tryptophan methyl, ethyl, propyl or isopropyl esters.
  • the related N-acetyl compounds may also include dimers and oligomers formed from N-acetylamino acids with 2 to 5 monomer units.
  • Examples include N-acetylglycylglycine and its amide and esters, N-acetylglycyl-leucine its amide and esters, N-acetylglycyltryptophan, N-acetylglycylglutamic acid and its amide and esters, N-acetyltryosyl-phenylalanine and its amide and esters, N-acetylglycyllysine and its amide and esters, N-acetylleucyl-glycine and its amide and esters, N-acetylglycyl-glycyl-glycine and its amide and esters, N-acetylglycyl-lysyl-hydroxyproline and its amide and esters.
  • N-Acetylamino acids and related compounds are the group of compounds represented by the generic structure or formula above, but excluding N-acetylcysteine and derivatives of N-acetylcysteine.
  • N-acetylcysteine is known to degrade under ordinary storage conditions and result in a malodorous smell. The malodor is suggested to be caused by the release of thiol compounds and hydrogen sulfide upon degradation. Because N-acetylcysteine and its derivatives are malodorous, they are less preferred for use in the present invention.
  • compositions comprising the N-acetyl-aldosamine, N-acetylamino acid or related N-acetyl compounds described herein are topically beneficial for various cosmetic conditions and dermatologic disorders, including those associated with intrinsic and/or extrinsic aging, as well as with changes or damage caused by extrinsic factors.
  • These compositions can comprise one or more than one N-acetylaldosamine, N-acetylamino acid or related N-acetyl compound.
  • the compositions may be used for skin, hair and nail changes associated with intrinsic and/or extrinsic aging, and changes or damage caused by extrinsic factors.
  • melanocytes Aberrant differentiation results in numerous foci of abnormal epithelial growths or tumors, the most frequent and important of which are actinic keratoses. After many years these can transform into frank skin cancers called basal cell and squamous cell cancers. Pigment producing cells (melanocytes) can also become altered forming flat, dark growths (lentigo melanoma) which may progress to malignant melanoms.
  • the cells which make the fibers of the dermis become smaller and sparser with increasing age, usually in sun-damaged facial skin. There is a great loss of collagen fibers resulting in looseness and easy stretchability of the skin; elastic fibers become abnormal so that the skin does not promptly snap back after being stretched. Since the fibrous components comprise more than 90% of the bulk of skin of which 95% is collagen, the degradation of these fibers, especially collagen, is mainly responsible for wrinkling, laxness and loss of elasticity.
  • the signs of nail and hair changes associated with intrinsic aging and the damages caused by extrinsic factors include thinning of hair and nail plate; lack of lubricants and luster, and uneven surface of hair and nails; fragility and splitting of hair and nails; and reduction of flexibility, resiliency, and elasticity of hair and nails.
  • Topical application to the skin, hair or nails of a composition of the present invention is beneficial for various cosmetic conditions and dermatologic disorders including those associated with intrinsic and/or extrinsic aging and extrinsic factors, and also including those characterized by the foregoing changes to the skin, hair and nails.
  • Exemplary indications are characterized as disturbed keratinization, defective syntheses of dermal components, and changes associated with aging of skin, nail and hair; and those indications which include dryness or loose of skin, nail and hair; xerosis; ichthyosis; palmar and plantar hyperkeratoses; uneven and rough surface of skin, nail and hair; dandruff; Darier's disease; lichen simplex chronicus; keratoses; acne; pseudofolliculitis barbae; eczema; psoriasis; itchy scalp and skin; pruritus; warts; herpes; age spots; lentigines; melasmas; blemished skin; hyperkeratoses; hyperpigmented skin; abnormal or diminished syntheses of collagen, glycosaminoglycans, proteoglycans and elastin as well as diminished levels of such components in the dermis; stretch marks; skin lines; fine lines; wrinkles; thinning of skin, nail
  • compositions comprising one or more than one N-Acetyl-aldosamine, N-acetylamino acid and related N-acetyl compound may also be incorporated into a composition comprising a cosmetic, pharmaceutical or other topical agent to enhance or create synergetic effects.
  • compositions of the present invention may contain one or more N-Acetyl-aldosamine, N-acetylamino acid and related N-acetyl compounds to magnify the therapeutic effect of an unrelated cosmetic or pharmaceutical agent.
  • At least one compound selected from the group consisting of N-Acetyl-aldosamine, N-acetylamino acid and related N-acetyl compounds may be incorporated into composition containing a cosmetic or pharmaceutical agent for topical treatment to improve or alleviate signs of skin, nails or hair changes associated with intrinsic aging or the damages caused by extrinsic factors. It has been found that such incorporation results in magnified therapeutic efficacies which are not simply additive effects.
  • the overall clinical effect would be a mixed effect, i.e. the effect due to the pharmaceutical agent alone mixed with the effect due to N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound alone.
  • the interaction between the pharmaceutical agent and its receptor molecule is not affected nor interfered by the presence of N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound.
  • the N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound assist in or enhance the binding affinity or the interaction of the pharmaceutical agent toward its receptor molecule.
  • the clinical results from such combination composition would be just the mixed effects.
  • N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound might interfere with or decrease the binding affinity of the pharmaceutical agent toward its receptor molecule; i.e. acting as an competitor or inhibitor.
  • the overall clinical results should be due to substantial diminishment or completely loss of therapeutic effects, which is also unpredictable from either effect alone.
  • the cosmetic and pharmaceutical agents which may be actuated by N-Acetyl-aldosamine, N-acetylamino acid or a related N-acetyl compound include those that improve or eradicate age spots, keratoses and wrinkles; local analgesics and anesthetics; antiacne agents; antibacterials; antiyeast agents; antifungal agents; antiviral agents; antidandruff agents; antidermatitis agents; antihistamine agents; antipruritic agents; antiemetics; antimotion sickness agents; antiinflammatory agents; antihyperkeratolytic agents; antiperspirants; antipsoriatic agents; antiseborrheic agents; hair conditioners and hair treatment agents; antiaging and antiwrinkle agents; sunblock and sunscreen agents; skin lightening agents; depigmenting agents; vitamins; corticosteroids; tanning agents; hormones; retinoids; and other dermatologicals.
  • cosmetic and pharmaceutical agents are clotrimazole, ketoconazole, miconazole, griseoflivin, econazole, metronidazole, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin, meclocycline, hydroquinone, hydroquinone monoether, minocycline, naproxen, ibuprofen, theophylline, cromolyn, albuterol, retinol, retinyl acetate, retinyl palmitate, retinal, retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone dipropionate, triamcinolone acetonide, fluo
  • N-acteyl-aldosamines, N-acetylamino acids or related N-acetyl compounds include hydroxyacids, ketoacids and related compounds.
  • hydroxy acids include hydroxymonocarboxylic acids, hydroxydicarboxylic acids, 2-hydroxycarboxylic acids, other hydroxycarboxylic, 2-ketocarboxylic acids acids and related compounds. See, for example, U.S. Pat. Nos. 5,422,370, 5,547,988, 5,470,880, and 5,385,938.
  • the hydroxy acids may exist as a free acid, an ester, a lactone, in salt form with an organic base or an inorganic alkali, and as stereoisomers.
  • Representative examples of hydroxy acids and related compounds include glycolic acid, mandelic acid, lactic acid, tropic acid, methyllactic acid, lactobionic acid, tartaric acid, citric acid, glucuronic acid, ribonic acid, gluconolactone, ribonolactone, gycolyl glycollate, lactyl lactate, trilactic acid and polylactic acid.
  • N-acteyl-aldosamines N-acetylamino acids or related N-acetyl compounds
  • phenyl alpha acyloxyalkanoic acids and derivatives thereof These compounds may exist in a free acid, lactone or salt form, or as stereoisomers. See, for example, U.S. Pat. Nos. 5,258,391 and 5,643,949.
  • Such compounds include diphenyl alpha acetoxyacetic acid, phenyl alpha acetoxyacetic acid, phenyl alpha methyl alpha acetoxyacetic acid, phenyl alpha acetoxypropanoic acid, and 2-phenyl beta acetoxypropanoic acid.
  • compositions comprising N-acetyl-aldosamine, N-acetylamino acid or related N-acetyl compounds of the instant invention may be formulated as solution, gel, lotion, cream, ointment, shampoo, spray, stick, powder, masque or other form topically acceptable for use on skin, nail and hair.
  • a solution composition at least one N-acetyl compound of the instant invention is dissolved in a solution prepared from water, ethanol, propylene glycol, butylene glycol, diisopropyl adipate and/or other topically acceptable vehicle.
  • concentration of a single N-acetyl compound or the total concentration of all N-acetyl compounds, where the composition comprises more than one N-acetyl compound may range from 0.01 to 99.9% by weight of the total composition, with preferred concentration of from 0.1 to 50% by weight of the total composition and with more preferred concentration of from 0.5 to 25% by weight of the total composition.
  • Contemplated embodiments of the instant invention include ranges of 0.1% to 0.2%, 0.2% to 0.3%, 0.3% to 0.4%, 0.4% to 0.5%, 0.5% to 0.6%, 0.6% to 0.7%, 0.7% to 0.8%, 0.8% to 0.9%, 0.9% to 1%, 1% to 2%, 2% to 3%, 3% to 4%, 4% to 5%, 5% to 6%, 6% to 7%, 7% to 8%, 8% to 9%, 9% to 10%, 10% to 14%, 14% to 18%, 18% to 22%, 22% to 26%, 26% to 30%, 30% to 35%, 35% to 40%, 40% to 45%, 45% to 50%, 50% to 60%, 60% to 70%, 70% to 80%, 80% n to 90%, and 90% to 99.9% by weight of the total composition.
  • the N-acetyl compound is first dissolved in water, ethanol, propylene glycol, diisopropyl adipate and/or another vehicle, and the solution thus obtained is mixed with a desired base or pharmaceutically acceptable vehicle to make lotion, cream or ointment. Concentrations of the N-acetyl compound are the same as described above for the solution form.
  • a topical composition of the instant invention may also be formulated in a gel or shampoo form.
  • a typical gel composition is formulated by the addition of a gelling agent such as chitosan, methyl cellulose, ethyl cellulose, polyvinyl alcohol, polyquaterniums, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carbomer or ammoniated glycyrrhizinate to a solution comprising the N-acetyl compound.
  • the preferred concentration of the gelling agent may range from 0.1 to 4 percent by weight of the total composition.
  • the N-acetyl compound is first dissolved in water or propylene glycol, and the solution thus obtained is mixed with a shampoo base. Concentrations of the N-acetyl compound used in gel or shampoo form are the same as described above.
  • a cosmetic, pharmaceutical or other topical agent is incorporated into any one of the above compositions by dissolving or mixing the agent into the formulation.
  • compositions for topical delivery of N-acetyl compound of the instant invention are readily prepared or formulated by those skilled in the art.
  • a typical N-acetyl-aldosamine, N-acetylamino acid or the related acetyl compound in a cream composition may be formulated as follows. N-Acetyl- ⁇ -D-glucosamine 10 g was dissolved in 30 ml warm water, and the solution thus obtained was mixed uniformly with 60 g cream base or commercially available hydrophilic ointment. The white cream thus formulated contained 10% N-acetyl-glucosamine. N-Acetyl-glucosamine 1% or 5% cream was formulated in the same manner except that N-acetyl- ⁇ -D-glucosamine 1 g or 5 g was used, and was dissolved in 39 ml or 35 ml water.
  • N-Acetyl-D-mannosamine 1 g was dissolved in 20 ml warm water, and the solution thus obtained was mixed uniformly with 79 g cream base or commercially available hydrophilic ointment.
  • the white cream thus formulated contained 1% N-acetyl-mannosamine.
  • N-Acetyl-L-glutamine 0.5 g was dissolved in 20 ml water, and the solution thus obtained was mixed uniformly with 79.5 g cream base or commercially available hydrophilic ointment.
  • the white cream thus formulated contained 0.5% N-acetyl-L-glutamine.
  • N-Acetyl-DL-proline 2 g was dissolved in 20 ml warm water, and the solution thus obtained was mixed uniformly with 78 g cream base or commercially available hydrophilic ointment.
  • the white cream thus formulated contained 2% N-acetyl-proline.
  • N-Acetyl-glycine 3 g was dissolved in 20 ml water, and the solution thus obtained was mixed uniformly with 77 g cream base or commercially available hydrophilic ointment.
  • the white cream thus formulated contained 3% N-acetyl-glycine.
  • N-Acetyl-L-arginine 4 g was dissolved in 20 ml water, and the solution thus obtained was mixed uniformly with 76 g cream base or commercially available hydrophilic ointment.
  • the white cream thus formulated contained 4% N-acetyl-arginine.
  • a typical N-acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound in a solution composition may be formulated as follows. N-acetyl- ⁇ -D-glucosamine 0.5 g was dissolved in 99.5 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition thus prepared contained 0.5% N-acetyl-glucosamine. N-Acetyl-glucosamine 5% in solution form was formulated in the same manner except that 5 g instead of 0.5 g active ingredient was dissolved in 95 ml solution.
  • N-Acetyl-D-galactosamine 1 g was dissolved in 99 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml.
  • the composition thus prepared contained 1% N-acetyl-galactosamine.
  • N-Acetyl-L-tyrosinamide 2 g was dissolved in 98 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml.
  • the composition thus prepared contained 2% N-acetyl-tyrosinamide.
  • N-Acetyl-L-lysine 0.5 g was dissolved in 99.5 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml.
  • the composition thus prepared contained 0.5% N-acetyl-lysine.
  • N-Acetyl-L-tyrosine 0.2 g was dissolved in 99.8 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml.
  • the composition thus prepared contained 0.2% N-acetyl-tyrosine.
  • N-Acetyl-L-cysteine methyl ester 0.5 g was dissolved in 99.5 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition thus prepared contained 0.5% N-acetyl-cysteine methyl ester.
  • N-Acetyl-L-tyrosine ethyl ester 3 g was dissolved in 97 ml solution prepared from ethanol 80 ml and propylene glycol 20 ml.
  • the composition thus prepared contained 3% N-acetyl-tyrosine ethyl ester.
  • N-acetyl-L-cysteine 2 g was dissolved in 98 ml solution prepared from water 80 ml and propylene glycol 20 ml.
  • the composition thus prepared contained 2% N-acetyl-cysteine.
  • a typical combination composition comprising for example N-acetyamino acid ester and hydrocortisone 17-valerate for eczema and other inflammatory dermatoses may be formulated as follows.
  • N-Acetyl-L-tyrosine ethyl ester 3 g and hydrocortisone 17-valerate 0.4 g were dissolved in 20 ml warm propylene glycol, and the solution thus obtained was mixed uniformly with 76.6 g cream base or commercially available hydrophilic ointment.
  • the white cream thus formulated had pH 5.1, and contained 3% N-acetyl-L-tyrosine ethyl ester and 0.4% hydrocortisone 17-valerate.
  • a typical combination composition comprising for example N-acetylaldosamine and an anti-itch agent may be formulated as follows.
  • N-Acetyl- ⁇ -D-glucosamine 2 g was dissolved in 10 ml water and the solution was mixed with diphenhydramine 2 g in 4 ml water containing 2 g gluconolactone. The above solution was mixed uniformly with 80 g cream base or commercially available hydrophilic ointment.
  • the composition with pH 5.1 contained 2% N-acetyl-D-glucosamine and 2% diphenhydramine.
  • N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compositions of the present invention may be applied to any area of the skin, hair, or nails.
  • Exemplary areas of application include the hands, arms, neck, legs, feet, trunk, hair shaft, nails, including the nail plate and nail cuticle, and on and around the face.
  • Exemplary areas of facial application include the nose, forehead, and areas around the eyes.
  • the compositions may be applied with or without occlusion. Any suitable occlusive device may be used. In addition, it is within the knowledge of the skilled artisan how best to apply such occlusive devices to achieve the desired result.
  • compositions of the present invention may be applied to these areas with varying frequency and for varying duration.
  • the skilled artisan will appreciate how to alter the frequency and duration of application to achieve the desired effect.
  • the compositions of the instant invention can be applied at varying frequencies including on a daily basis, 1 or more times daily, or 1 or more times weekly.
  • the instant invention can be applied 1, 2, 3 or more times a day.
  • the instant invention can be applied 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more times a week.
  • the duration of treatment with the compositions of the instant invention can also vary.
  • the compositions may be applied for 1, 2, 3, 4, 5, 6 or more weeks; or for 1, 2, 3, 4, 5, 6 or more months.
  • the duration of treatment may also be continuous. Again, the skilled artisan will appreciate the interaction between frequency and duration of use in order to achieve and/or maintain the desired effect.
  • concentrations of the instant invention in conjunction with the frequency and duration of use to achieve the desired effect. For example, a composition of higher concentration might be applied with less frequency or for a shorter duration. In contrast, a composition of a lower concentration might be applied more frequently or for a longer duration.
  • skin thickness was measured by micrometer calipers as follows: The skin was grasped with a 2 ⁇ 6 cm metal hinge, the internal faces of the hinge were coated with emery cloth to prevent slippage, and manually squeezed to threshold subject discomfort. Combined thickness of two whole-skin layers including thickness of the two hinge leaves was measured with micrometer calipers. Thickness of the two hinge leaves was subtracted to determine the actual thickness of two whole-skin layers. Triplicate measurements on treated site were done and an average number was used for calculation of the skin thickness.
  • N-acetyl-glucosamine was therapeutically effective for topical treatment of xerosis and dry skin.
  • N-acetyl-glucosamine was therapeutically effective for topical treatment of acne.
  • Test sites were 1 cm square sites on extensor surface of forearm, 5 cm from the antecubital crease, a grid pattern formed by Hayes Test Chambers on Hayes adhesive strips. Each test chamber, 1 cm square, contained a square piece of filter paper which was fully moistened with 0.033 ml test solution.
  • Test chambers were impressed on the skin to leave outlines which were marked with Sanford Sharpie permanent marker. Sites were re-marked at each successive application of test solutions. Vehicle control sites were on the opposite forearm. Filter paper of each chamber was saturated with 0.033 ml solution and chambers were fixed in place with the Hayes adhesive tape that held the test and vehicle chambers. Chambers were removed twice weekly, and replaced with a new adhesive strip of chambers with filter paper moistened with test or vehicle solutions. The test was carried out for five weeks. Punch biopsy specimens, 3 mm or 4 mm in diameter, were secured at the end of the study, and specimens were processed and analyzed. Measurements of several tissue characteristics were also made.
  • Epidermal thickness was measured with Micro Image Analysis System, and the mean thickness was expressed as area of epidermis/horizontal length. The thickness of papillary dermis (upper dermis) was also measured.
  • All the skin sites treated with N-acetyl-cysteine showed an average of 96% increase in thickness of epidermis over the control.
  • all the test sites showed 47-227% increase in production of hyaluronic acid in papillary dermis over the control.
  • N-acetyl compounds of the instant invention would be topically beneficial for treatment of various cosmetic or dermatologic indications including wrinkles and changes of skin, nail and hair associated with intrinsic and extrinsic aging.
  • N-acetyl-DL-homocysteine thiolactone cream applied topically twice daily 5% N-acetyl-DL-homocysteine thiolactone cream to his right forearm for three weeks. After three weeks his untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, his right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of his left forearm, his right forearm had increased 89% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-homocysteine thiolactone would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
  • N-acetyl-L-cysteine cream A female subject, age 71, applied topically twice daily 5% N-acetyl-L-cysteine cream to her right forearm for three weeks. After three weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 14% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-cysteine would be therapeutically effective for topical treatment of wrinkles and changes of skin, nails or hair associated with aging.
  • N-acetyl-L-cysteine methyl ester cream A female subject, age 59, applied topically twice daily 5% N-acetyl-L-cysteine methyl ester cream to her right forearm for three weeks. After three weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 13% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-cysteine methyl ester would be therapeutically effective for topical treatment of wrinkles and changes of skin, nails or hair associated with aging.
  • N-acetyl-L-cysteine methyl ester cream A male subject, age 76, applied topically twice daily 5% N-acetyl-L-cysteine methyl ester cream to his left forearm for three weeks. After three weeks his untreated right forearm was still loose, relatively thin and wrinkled when lifted. In contrast, his left forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of his right forearm, his left forearm had increased 87% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-cysteine methyl ester would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
  • N-acetyl-L-tyrosine ethyl ester would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
  • N-acetyl-DL-tryptophan cream A female subject, age 56, applied topically twice daily 10% N-acetyl-DL-tryptophan cream to her right forearm for three weeks. After three weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 21% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-tryptophan would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
  • N-acetyl-L-arginine cream A female subject, age 47, applied topically twice daily 10% N-acetyl-L-arginine cream to her right forearm for four weeks. After four weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 32% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-L-arginine would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
  • N-acetyl-L-tyrosine ethyl ester cream A female subject, age 72, applied topically twice daily 10% N-acetyl-L-tyrosine ethyl ester cream to her right forearm for four weeks. After four weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 34% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-tyrosine ethyl ester would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
  • N-acetyl-L-arginine cream A female subject, age 72, applied topically twice daily 10% N-acetyl-L-arginine cream to her left forearm for four weeks. After four weeks her untreated right forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her left forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her right forearm, her left forearm had increased 22% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-arginine would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
  • her untreated left forearm was still loose, relatively thin and wrinkled when lifted.
  • her right forearm was more firm, smooth, plump and minimally wrinkled when lifted.
  • a typical composition suitable for topical use on hair, scalp, nail and skin comprising for example N-acetylamino acid may be formulated as follows. N-Acetyl-DL-proline 2 g was dissolved in 98 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition with pH 2.7 contained 2% N-acetyl-DL-proline. A male subject, age 66, having itchy scalp topically applied the above composition to itchy area of scalp. A few minutes after the topical application, scalp itch disappeared completely and the scalp remained free of itch for the next 24 hours.
  • a typical composition comprising for example N-acetylamino acid in combination with an anti-fungal agent for nail or scalp infections may be formulated as follows.
  • N-Acetylglycine 2 g was dissolved in 98 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml.
  • the composition thus prepared contained 2% N-acetylglycine, and was used as a nail or scalp conditioner.
  • N-acetylglycine 2 g and clotrimazole 2 g were dissolved in 96 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml.
  • the composition with pH 3.7 contained 2% N-acetylglycine and 2% clotrimazole, and were topically effective for nail or scalp infections.
  • a typical shampoo composition comprising for example N-acetylamino acid for hair, scalp or body wash may be formulated as follows. N-Acetyl-L-arginine 4 g was dissolved in 20 ml water, and the solution thus obtained was mixed uniformly with 76 g shampoo base. The shampoo composition with pH 6.6 contained 4% N-acetyl-L-arginine
  • N-Acetyl-L-lysine 2 g was dissolved in a 98 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml.
  • the composition with pH 6.5 contained 2% N-acetyl-L-lysine.
  • a male subject, age 66, having an oily and pruritic scalp topically applied the above composition to the affected area of the scalp, and the area was dried with warm air to remove excess solvents. A few minutes after the topical application, the scalp itch disappeared completely and the scalp remained free of itch the next 12 hours.
  • the subject topically applied N-acetyl-DL-proline 5% in oil-in-water cream to the itchy lesions.
  • a female subject, age 72, having acute urticaria due to unknown cause did not respond to conventional topical anti-itch medications.
  • the subject topically applied N-acetyl-D-galactosamine 5% in solution to skin areas of the urticarial lesions.
  • a few minutes after the topical application the severe itch disappeared completely and the skin remained free of itch for the next 24 hours with concomitant disappearance of urticarial lesions.
  • the subject topically applied N-acetyl-L-glutamine 5% in a solution prepared from water 4 parts, ethanol 4 parts and propylene glycol 2 parts by volume. A few minutes after the topical application, the severe itch disappeared completely and the lesions remained free of itch for the next 24 hours.
  • the subject topically applied N-acetyl- ⁇ -D-glucosamine 5% in a solution prepared from water 4 parts, ethanol 4 parts and propylene glycol 2 parts by volume. A few minutes after the topical application, the severe itch disappeared completely and the lesions remained free of itch for the next 24 hours.

Abstract

Compositions comprising N-acetyl-aldosamines, N-acetylamino acids, and related N-acetyl compounds are useful to alleviate or improve various cosmetic conditions and dermatological disorders, including changes or damage to skin, nail and hair associated with intrinsic aging and/or extrinsic aging, as well as changes or damage caused by extrinsic factors. N-acetyl-aldosamines, N-acetylamino acids, and related N-acetyl composition may further comprise a cosmetic, pharmaceutical or other topical agent to enhance or create synergetic effects.

Description

Notice: This is a continuation reissue application of continuation reissue application Ser. No. 12/536,209 filed Aug. 5, 2009, now Reissue U.S. Pat. No. Re. 42,902, which is a continuation reissue application of reissue application Ser. No. 11/590,898 filed Nov. 1, 2006, now Reissue U.S. Pat. No. Re. 41,339, which is a reissue application of U.S. Pat. No. 6,159,485.
FIELD OF THE INVENTION
This application relates to topical compositions containing N-acetyl-aldosamines, N-acetylamino acids, and related N-acetyl compounds, and their use in alleviating or improving various cosmetic conditions and dermatological disorders including signs of aging, changes or damage to skin, nail and hair associated with intrinsic aging and/or extrinsic aging, as well as changes or damage caused by extrinsic factors such as sunlight, radiation, air pollution, wind, cold, heat, dampness, chemicals, smoke, and cigarette smoking; and for certain skin disorders associated with or due to itching and/or inflammation.
BRIEF DESCRIPTION OF THE PRIOR ART
In our U.S. Pat. No. 5,091,171 we described and claimed preventive as well as therapeutic treatment to alleviate cosmetic conditions and symptoms of dermatologic disorders with amphoteric compositions containing alpha hydroxyacids, alpha ketoacids, polymeric forms of hydroxyacids, and related compounds or. In our U.S. Pat. No. 5,547,988, and related patents, we described the use of topical compositions comprising a 2-hydroxycarboxylic acid or related compound to alleviate or improve signs of skin, nail and hair changes associated with intrinsic or extrinsic aging. In our U.S. Pat. No. 5,385,938, and related patents, we described preventive and therapeutic treatment to alleviate cosmetic conditions and symptoms of dermatologic disorders with amphoteric compositions containing alpha hydroxy acids, alpha ketoacids, polymeric forms of hydroxy acids, and related compounds or. In our U.S. Pat. No. 5,258,391 entitled “Phenyl Alpha Acyloxyalkanoic Acids, Derivatives and Their Therapeutic Use” we described and claimed the use of topical compositions containing phenyl alpha acyloxyalkanoic acids and derivatives to enhance the keratization of nails, skin, lips and other mucous membranes. In our U.S. Pat. No. 5,665,776 entitled “Additives Enhancing Topical Actions of Therapeutic Agents” we described and claimed the use of hydroxycarboxylic acids or related compounds to increase the cosmetic or therapeutic effect of cosmetic or pharmaceutical agents. In our U.S. Pat. No. 5,641,475 we described and claimed the use of topical compositions containing a bioactive cosmetic, dermatologic or preservative agent and aryl 2-acetoxyethanoic acid effective as a synergist or amplifier. In our U.S. Pat. No. 5,643,949 also entitled “Phenyl Alpha Acyloxyalkanoic Acids, Derivatives and Their Therapeutic Use” we described and claimed the use of topical compositions containing a cosmetic or dermatologic drug for topical administration to nails, skin and lips and an amount of a phenyl alpha acyloxyalkanoic acid or derivatives effective to enhance the cosmetic or therapeutic effect of the dermatologic drug. In U.S. Pat. No. 4,603,146 to Albert M. Kligman, disclosure is made of the use of vitamin A (tretionoin) to reduced and prevent epithelial growths and aid the skin in regaining and maintaining firmness, turgor and elasticity.
In a report entitled “Topical Tretinoin for Photoaged Skin” by Kligman et al., J. American Academy of Dermatology, Vol. 15, pages 836-859, 886-887 (1986), daily topical application of 0.05% tretinoin (also known as all-transretinoic acid) in a cream has been found to improve photodamaged skin. In another report entitled “Topical Tretinoin Improves Photoaged Skin: A Double-blind Vehicle-controlled Study” by Weiss et al., J. American Medical Association, Vol. 259 pages 527-532 (1988), daily topical application of 0.1% tretinoin as compared to vehicle alone application for 16 weeks has been shown to improve photoaged skin. One side-effect has been a dermatitis encountered by 92% of the patients participating in this study. The dermatitis was characterized by a patchy erythema, localized swelling, dry skin, and mild scaling. Patients complained about burning, tingling, or pruritus. In yet another report entitled “Topical Tretinoin in the Treatment of Aging Skin” by Weiss et al., J. American Academy of Dermatology Vol. 19, pages 169-175 (1988), topical application of 0.1% tretinoin cream for 8 to 12 months has been found to improve clinical signs of aging skin. The side effects have been burning sensation in the eyes and mild skin irritations.
In PCT Application No. PCT/US96/16534, filed Oct. 16, 1996, entitled “Topical Compositions Containing N-Acetylcysteine and Odor Masking Materials,” topical compositions comprising from 0.01% to 50% of N-acetylcysteine or a derivative of N-acetylcysteine, from 0.01% to 0.5% of an odor masking material, and a topical carrier are disclosed to improve the appearance of skin.
N-Acetylcysteine is N-acetylated cysteine which is a thiol containing amino acid, also called α-acetamido-β-mercaptopropanoic acid. Topical compositions containing N-acetylcysteine have been claimed to improve physical appearance of the skin including cosmetic wrinkles. N-acetylcysteine contains a free thiol group, thus, is known as an antioxidant. The affect of N-acetylcysteine is claimed to be due to its antioxidant property. N-Acetylcysteine, as an antioxidant substance, also has been indicated as protective against pulmonary oxygen toxicity (Eur. Respir. J. 2, 116-126, 1989).
N-acetylcysteine, however, is also associated with a number of significant drawbacks. N-acetylcysteine is known to degrade under ordinary storage conditions and result in a malodorous smell. The malodor is suggested to be caused by the release of thiol compounds and hydrogen sulfide upon degradation. Thus, topical compositions containing N-acetylcysteine have little or no commercial use due to the strong malodor of N-acetylcysteine.
PCT/US96/16534 claimed that the malodor could be masked by addition of certain perfume chemicals at concentrations ranging from 0.01 to 0.5% by weight. The perfume chemicals include aromatic esters, aliphatic esters, aromatic alcohol, aliphatic alcohols, aliphatic ketones, aromatic aldehydes, aliphatic aldehydes, aromatic ethers and aliphatic ethers. Because the malodorous thiol compounds and hydrogen sulfide have not been chemically neutralized or destroyed, however, the transient masking effect is not a satisfactory solution for most consumers, and therefore is not a viable approach for commercialization of N-acetylcysteine in cosmetic industry.
We have now discovered that N-aldosamines, N-acetylated amino acids and related compounds are topically effective for various cosmetic conditions and dermatological indications including the signs of skin, nail and hair changes associated with intrinsic and/or extrinsic aging. The N-acetylated amino acids and related compounds do not necessarily contain thiol groups and are not necessarily antioxidants.
SUMMARY OF THE INVENTION
Accordingly, it is an object of this invention to provide methods and compositions which can alleviate various cosmetic conditions and dermatological disorders including the signs of skin, nail and hair changes associated with intrinsic and/or extrinsic aging and extrinsic factors, and other skin conditions associated with or due to itching and/ or inflamation, including pruritus.
We have now discovered that N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds have unexpected properties. Topical applications of compositions comprising N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds have been found to improve cosmetic conditions and dermatological disorders including cosmetic as well as clinical signs of changes in skin, nails and hair associated with intrinsic and/or extrinsic aging, or the damages caused by extrinsic factors such as sunlight, radiation, air pollution, wind, cold, dampness, heat, chemicals, smoke, and cigarette smoking.
The signs of skin changes associated with intrinsic and/or extrinsic aging and the skin damages caused by extrinsic factors include thinning of skin; fragile skin; deepening of skin lines and fine lines; wrinkles, including fine and course wrinkles; blemishes; atrophy; pigmented spots, blotches and mottles, nodules and mottled skin; pre-cancerous lesions; elastotic changes characterized by leathery, lusterless, uneven, coarse, rough, dry and/or yellowish skin; loss of skin elasticity and recoilability; loss of skin lubricating substances; changes in qualities and quantities of glycosaminoglycans and proteoglycans and collagen and elastic fibers; solar elastosis; decrease in collagen fibers; diminution in the number and diameter of elasitic fibers in the papillary dermis; atrophy; stretch marks; reduction in subcutaneous adipose tissue; deposition of abnormal elastic materials in the dermis leading to thickening of the dermis; older-looking skin; and telangiectatic skin.
The signs of nails and hair changes associated with intrinsic aging and the damages caused by extrinsic factors include thinning, fragility, splitting, lack of luster, uneven surface, and loss of flexibility and elasticity.
In accordance with the objects of the invention, a composition comprising at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids and related compounds, present in a therapeutically effective amount and in a pharmaceutically acceptable vehicle for topical treatment of cosmetic conditions or dermatological disorders is provided. In one embodiment of the invention, the composition further comprises a cosmetic, pharmaceutical, or other topical agent.
Also in accordance with the objects of the invention, a method for treating cosmetic conditions and dermatological disorders comprising topically applying a therapeutically effective amount of a composition comprising at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids and related compounds, in a pharmaceutically acceptable vehicle is provided. In one embodiment of the invention, the method comprises topically applying a therapeutically effective amount of a composition comprising at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids and related compounds, and at least one cosmetic, pharmaceutical, or other topical agent, in a pharmaceutically acceptable vehicle.
N-Acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds which are useful for topical treatment of skin, nail and hair changes associated with intrinsic and/or extrinsic aging and extrinsic factors include, inter alia, N-acetyl-aldosamines which are derivatives of aminosugars and include N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-glucosamine, N-acetyl-galactosamine and N-acetyl-mannosamine, and N-acetylamino acids which are N-acetyl derivatives of amino acids and include N-acetyl-glycine, N-acetyl-proline, N-acetyl-lysine, N-acetyl-arginine and N-acetyl-tryptophan.
Additional objects and advantages of the invention will be set forth in part in the description that follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and the advantages of this invention may be realized and obtained by means of the compositions and methods particularly pointed out in the appended claims.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 1. N-Acetyl-aldosamines, N-Acetylamino Acids and Related N-Acetyl Compounds (i) N-Acetyl-aldosamines
One aspect of the present invention pertains to compositions comprising N-acetyl-aldosamines and related compounds. N-acetyl-aldosamines are N-acetylated aminosugars in which the acetylamino group is preferably located at position 2 of the carbon chain. In accordance with the present invention, the generic structure or formula of N-acetyl-aldosamines which are topically beneficial for various cosmetic and dermatologic indications may be represented as follows:
Figure USRE044302-20130618-C00001

where n is an integer, preferably 1-19; R1 is selected from the group consisting of CHO, CONH2, and COOR3; R2 is selected from the group consisting of H, l, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated, isomeric or non-isomeric, straight or branched chain or cyclic form, having 1 to 19 carbon atoms; and R3 is selected from the group consisting of H, an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms. N-Acetyl-aldosamines may be present as saturated or unsaturated, isomeric or non-isomeric, straight or branched chain or cyclic form. A typical cyclic form of an N-acetyl-aldosamine is a five member ring (furanose form) or a six member ring (pyranose form).
The following are some representative N-acetyl-aldosamines and related compounds: N-acetyl-glycerosamine, N-acetyl-erythrosamine, N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine, N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine, N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine, N-acetyl-talosamine, N-acetyl-glucoheptosamine, N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine, N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine, N-acetylneuramin Lactose, N-acetyl-glyceraminic acid, N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid, N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid, N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid, N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid, N-acetyl-glucosaminic acid, N-acetyl-mannosaminic acid, N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid, N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid, N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid, N-acetyl-heptomannosaminic acid, and N-acetyl-N-acetylneuraminic. The amides and esters of the foregoing acid compounds also are contemplated by the present invention. Examples of five and six member ring forms are 2-acetamido-2-deoxy-D-ribofuranoside, 2-acetamido-2-deoxy-D-ribopyranoside, 2-acetamido-2-deoxy-D-glucofuranoside, 2-acetamido-2-deoxy-D-glucopyranoside, 2-acetamido-2-deoxy-D-galactofuranoside and 2-acetamido-2-deoxy-D-galactopyranoside.
(ii) N-Acetylamino Acids
Another aspect of the invention pertains to compositions comprising N-acetylamino acids and related compounds. N-acetylamino acids are N-acetyl derivatives of amino acids. In accordance with the present invention, the generic structure or formula of N-acetylamino acids and related compounds which are topically beneficial for various cosmetic and dermatologic indications may be represented as follows:
Figure USRE044302-20130618-C00002

where R1 is H, or an alkyl or aralkyl group having 1 to 14 carbon atoms; n is an integer, preferably from 0 to 5; R2 is OH, NH2 or OR3; and R3 is an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms; the alkyl, aralkyl or aryl group may be saturated or unsaturated, isomeric or non-isomeric, straight or branched chain or cyclic form; and in addition R1 may carry OH, SH, SCH3, COOH, NH2CONH2, guanidine or heterocyclic group; the H attached to a carbon atom may be substituted by I, F, Cl, Br or alkoxyl group having 1 to 9 carbons. N-Acetylamino acids may be present as isomeric or non-isomeric, as a free acid, salt, lactone, amide or ester form.
The following are some representative N-acetylamino acids and related compounds: N-acetyl-glycine, N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl-serine, N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-cysteine, N-acetyl-methionine, N-acetyl-aspartic acid, N-acetyl-asparagine, N-acetyl-glutamic acid, N-acetyl-glutamine, N-acetyl-arginine, N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine, N-acetyl-tryptophan, N-acetyl-proline, N-acetyl-β-alanine, N-acetyl-taurine, N-acetyl-r-aminobutanoic acid, N-acetyl-hydroxyproline, N-acetyl-canavanine, N-acetyl-hydroxylysine, N-acetyl-cycloserine, N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline, N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline, N-acetylethionine, N-acetyl-methoxinine, N-acetyl-β-aminoisobutanoic acid, N-acetyl-homocysteine, N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine, N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine (N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine, N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa, N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine, N-acetyl-3,5,3′-triiodothyronine, N-acetyl-thyroxine, N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine and N-acetyl-homocystine.
The above N-acetylamino acids and related N-acetyl compounds may be present as a free acid, salt, lactone, amide or ester form. Examples of these compounds include N-acetyl-cysteine ammonium salt, N-acetyl-homocysteine thiolactone, N-acetyl-L-cystine methyl ester, N-acetyl-L-tryosinamide, N-acetyl-L-tryosine ethyl ester, N-acetyl-serine amide, N-acetylglycine methyl ester, N-acetylglycinamide, and N-acetyl-tryptophan methyl, ethyl, propyl or isopropyl esters.
The related N-acetyl compounds may also include dimers and oligomers formed from N-acetylamino acids with 2 to 5 monomer units. Examples include N-acetylglycylglycine and its amide and esters, N-acetylglycyl-leucine its amide and esters, N-acetylglycyltryptophan, N-acetylglycylglutamic acid and its amide and esters, N-acetyltryosyl-phenylalanine and its amide and esters, N-acetylglycyllysine and its amide and esters, N-acetylleucyl-glycine and its amide and esters, N-acetylglycyl-glycyl-glycine and its amide and esters, N-acetylglycyl-lysyl-hydroxyproline and its amide and esters.
A preferred group N-Acetylamino acids and related compounds are the group of compounds represented by the generic structure or formula above, but excluding N-acetylcysteine and derivatives of N-acetylcysteine. N-acetylcysteine is known to degrade under ordinary storage conditions and result in a malodorous smell. The malodor is suggested to be caused by the release of thiol compounds and hydrogen sulfide upon degradation. Because N-acetylcysteine and its derivatives are malodorous, they are less preferred for use in the present invention.
2. Topical Uses of N-Acetyl-aldosamines, N-Acetylamino Acids and Related N-Acetyl Compounds (i) N-Acetyl-aldosamines, N-Acetylamino Acids and Related N-Acetyl Compounds
Compositions comprising the N-acetyl-aldosamine, N-acetylamino acid or related N-acetyl compounds described herein are topically beneficial for various cosmetic conditions and dermatologic disorders, including those associated with intrinsic and/or extrinsic aging, as well as with changes or damage caused by extrinsic factors. These compositions can comprise one or more than one N-acetylaldosamine, N-acetylamino acid or related N-acetyl compound. In a preferred embodiment, the compositions may be used for skin, hair and nail changes associated with intrinsic and/or extrinsic aging, and changes or damage caused by extrinsic factors.
With respect to age associated skin changes, the underlying bases of these changes is described in U.S. Pat. No. 4,603,146 (Kligman). In particular, the underlying causes of skin changes associated with aging can be more easily understood in view of the following summary of the changes in the epidermis and dermis as aging progresses.
With increasing age and exposure of a human to sun and other environmental traumas, cells divide at a slower rate (decreased capacity to renew themselves). They show marked irregularities in size, shape and staining properties; orderliness (polarity) from below to above is lost. The thickness of the epidermis decreases (atrophy). The horny layer which comprises the barrier against water loss and penetration of chemicals becomes abnormal due to the shedding (exfoliation) of cells in large group or clusters instead of as individual cells, resulting in roughness, scaling and dryness. There is loss of the orderly transformation of living epithelial cells into cornified dead cells which are shed at the surface, that is, differentiation is impaired. Aberrant differentiation results in numerous foci of abnormal epithelial growths or tumors, the most frequent and important of which are actinic keratoses. After many years these can transform into frank skin cancers called basal cell and squamous cell cancers. Pigment producing cells (melanocytes) can also become altered forming flat, dark growths (lentigo melanoma) which may progress to malignant melanoms.
The cells which make the fibers of the dermis become smaller and sparser with increasing age, usually in sun-damaged facial skin. There is a great loss of collagen fibers resulting in looseness and easy stretchability of the skin; elastic fibers become abnormal so that the skin does not promptly snap back after being stretched. Since the fibrous components comprise more than 90% of the bulk of skin of which 95% is collagen, the degradation of these fibers, especially collagen, is mainly responsible for wrinkling, laxness and loss of elasticity.
Additionally, small blood vessels become thin walled, dilated and often ruptured. Vascular supply thereby becomes compromised.
The signs of nail and hair changes associated with intrinsic aging and the damages caused by extrinsic factors include thinning of hair and nail plate; lack of lubricants and luster, and uneven surface of hair and nails; fragility and splitting of hair and nails; and reduction of flexibility, resiliency, and elasticity of hair and nails.
The conventional management of signs of aging skin has been the use of cosmetics, as well as medical procedures such as phenol, trichloroacetic acid, and other chemical peels, and plastic surgery, etc. Such medical procedures are costly and risky with serious side effects, and the treatments alter only the cosmetic appearance of the skin, without any significant modifications of the underlying aging process.
Topical application to the skin, hair or nails of a composition of the present invention is beneficial for various cosmetic conditions and dermatologic disorders including those associated with intrinsic and/or extrinsic aging and extrinsic factors, and also including those characterized by the foregoing changes to the skin, hair and nails. Exemplary indications are characterized as disturbed keratinization, defective syntheses of dermal components, and changes associated with aging of skin, nail and hair; and those indications which include dryness or loose of skin, nail and hair; xerosis; ichthyosis; palmar and plantar hyperkeratoses; uneven and rough surface of skin, nail and hair; dandruff; Darier's disease; lichen simplex chronicus; keratoses; acne; pseudofolliculitis barbae; eczema; psoriasis; itchy scalp and skin; pruritus; warts; herpes; age spots; lentigines; melasmas; blemished skin; hyperkeratoses; hyperpigmented skin; abnormal or diminished syntheses of collagen, glycosaminoglycans, proteoglycans and elastin as well as diminished levels of such components in the dermis; stretch marks; skin lines; fine lines; wrinkles; thinning of skin, nail plate and hair; skin thickening due to elastosis of photoaging, loss or reduction of skin, nail and hair resiliency, elasticity and recoilability; lack of skin, nail and hair lubricants and luster; dull and older-looking skin, nail and hair; fragility and splitting of nail and hair; and other topical conditions and indications.
(ii) Combination Compositions
In addition, compositions comprising one or more than one N-Acetyl-aldosamine, N-acetylamino acid and related N-acetyl compound may also be incorporated into a composition comprising a cosmetic, pharmaceutical or other topical agent to enhance or create synergetic effects.
In accordance with this aspect of the invention, the compositions of the present invention may contain one or more N-Acetyl-aldosamine, N-acetylamino acid and related N-acetyl compounds to magnify the therapeutic effect of an unrelated cosmetic or pharmaceutical agent. At least one compound selected from the group consisting of N-Acetyl-aldosamine, N-acetylamino acid and related N-acetyl compounds may be incorporated into composition containing a cosmetic or pharmaceutical agent for topical treatment to improve or alleviate signs of skin, nails or hair changes associated with intrinsic aging or the damages caused by extrinsic factors. It has been found that such incorporation results in magnified therapeutic efficacies which are not simply additive effects.
Most pharmaceutical drugs produce their therapeutic effects by first interacting with their receptors in the target tissues. Many drug receptors are functional macromolecules such as enzymes, cell membrane components or certain components of cells. The binding affinity or interacting property of a drug toward its specific receptor molecule is intimately governed by the chemical structure of the drug. Since most pharmaceutical agents are chemically different from N-acetyl compounds of the instant invention, the respective receptor molecule should be different and so are the pharmacological actions and the therapeutic effects. Under such conditions if N-Acetyl-aldosamine, N-acetylamino acid and/or a related N-acetyl compound is incorporated into a composition containing a pharmaceutical agent, one of the following two consequences may arise:
(a) No enhancement or any substantial changes in either effect. In this case, the overall clinical effect would be a mixed effect, i.e. the effect due to the pharmaceutical agent alone mixed with the effect due to N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound alone. Also in this case, the interaction between the pharmaceutical agent and its receptor molecule is not affected nor interfered by the presence of N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound. Nor does the N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound assist in or enhance the binding affinity or the interaction of the pharmaceutical agent toward its receptor molecule. The clinical results from such combination composition would be just the mixed effects.
(b) Amplified therapeutic action or substantial loss of therapeutic action in either effect. In this case, the interaction between the pharmaceutical agent and its receptor molecule is affected either positively or negatively by the presence of a N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound. From the point of positive effect, N-Acetyl-aldosamine, N-acetylamino acid or the related N-acetyl compound may produce an amplified effect by either increasing the affinity of the receptor molecule toward the pharmaceutical agent; acting as a better and more efficient coenzyme or as an activator by disrupting barriers and removing obstacles for better binding of the agent toward its receptor molecule; for example, enzyme activation by removal of natural inhibitors. In all these cases the overall clinical results would be due to magnified therapeutic effects which are not predictable from either effect alone.
From the point of negative effect, a N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound might interfere with or decrease the binding affinity of the pharmaceutical agent toward its receptor molecule; i.e. acting as an competitor or inhibitor. In such case, the overall clinical results should be due to substantial diminishment or completely loss of therapeutic effects, which is also unpredictable from either effect alone.
We have found that, in most cases, therapeutic effects of cosmetic and pharmaceutical agents are amplified when a N-acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound is incorporated into the composition, i.e., consequence (b) above is observed.
The cosmetic and pharmaceutical agents which may be actuated by N-Acetyl-aldosamine, N-acetylamino acid or a related N-acetyl compound include those that improve or eradicate age spots, keratoses and wrinkles; local analgesics and anesthetics; antiacne agents; antibacterials; antiyeast agents; antifungal agents; antiviral agents; antidandruff agents; antidermatitis agents; antihistamine agents; antipruritic agents; antiemetics; antimotion sickness agents; antiinflammatory agents; antihyperkeratolytic agents; antiperspirants; antipsoriatic agents; antiseborrheic agents; hair conditioners and hair treatment agents; antiaging and antiwrinkle agents; sunblock and sunscreen agents; skin lightening agents; depigmenting agents; vitamins; corticosteroids; tanning agents; hormones; retinoids; and other dermatologicals.
Some examples of cosmetic and pharmaceutical agents are clotrimazole, ketoconazole, miconazole, griseoflivin, econazole, metronidazole, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin, meclocycline, hydroquinone, hydroquinone monoether, minocycline, naproxen, ibuprofen, theophylline, cromolyn, albuterol, retinol, retinyl acetate, retinyl palmitate, retinal, retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone dipropionate, triamcinolone acetonide, fluocinonide, clobetasol, propionate, benzoyl peroxide, kojic acid, crotamiton, propranolol, promethazine, salicylic acid, vitamin E and vitamin E acetate.
Another example of cosmetic or other agents that may be combined with one or more N-acteyl-aldosamines, N-acetylamino acids or related N-acetyl compounds include hydroxyacids, ketoacids and related compounds. Examples of hydroxy acids include hydroxymonocarboxylic acids, hydroxydicarboxylic acids, 2-hydroxycarboxylic acids, other hydroxycarboxylic, 2-ketocarboxylic acids acids and related compounds. See, for example, U.S. Pat. Nos. 5,422,370, 5,547,988, 5,470,880, and 5,385,938. The hydroxy acids may exist as a free acid, an ester, a lactone, in salt form with an organic base or an inorganic alkali, and as stereoisomers. Representative examples of hydroxy acids and related compounds include glycolic acid, mandelic acid, lactic acid, tropic acid, methyllactic acid, lactobionic acid, tartaric acid, citric acid, glucuronic acid, ribonic acid, gluconolactone, ribonolactone, gycolyl glycollate, lactyl lactate, trilactic acid and polylactic acid.
Yet another example of cosmetic or other agents that may be combined with one or more N-acteyl-aldosamines, N-acetylamino acids or related N-acetyl compounds include phenyl alpha acyloxyalkanoic acids and derivatives thereof. These compounds may exist in a free acid, lactone or salt form, or as stereoisomers. See, for example, U.S. Pat. Nos. 5,258,391 and 5,643,949. Representative example of such compounds include diphenyl alpha acetoxyacetic acid, phenyl alpha acetoxyacetic acid, phenyl alpha methyl alpha acetoxyacetic acid, phenyl alpha acetoxypropanoic acid, and 2-phenyl beta acetoxypropanoic acid.
3. General Preparation of the Cosmetic and Therapeutic Compositions
Compositions comprising N-acetyl-aldosamine, N-acetylamino acid or related N-acetyl compounds of the instant invention may be formulated as solution, gel, lotion, cream, ointment, shampoo, spray, stick, powder, masque or other form topically acceptable for use on skin, nail and hair.
To prepare a solution composition, at least one N-acetyl compound of the instant invention is dissolved in a solution prepared from water, ethanol, propylene glycol, butylene glycol, diisopropyl adipate and/or other topically acceptable vehicle. The concentration of a single N-acetyl compound or the total concentration of all N-acetyl compounds, where the composition comprises more than one N-acetyl compound, may range from 0.01 to 99.9% by weight of the total composition, with preferred concentration of from 0.1 to 50% by weight of the total composition and with more preferred concentration of from 0.5 to 25% by weight of the total composition. Contemplated embodiments of the instant invention include ranges of 0.1% to 0.2%, 0.2% to 0.3%, 0.3% to 0.4%, 0.4% to 0.5%, 0.5% to 0.6%, 0.6% to 0.7%, 0.7% to 0.8%, 0.8% to 0.9%, 0.9% to 1%, 1% to 2%, 2% to 3%, 3% to 4%, 4% to 5%, 5% to 6%, 6% to 7%, 7% to 8%, 8% to 9%, 9% to 10%, 10% to 14%, 14% to 18%, 18% to 22%, 22% to 26%, 26% to 30%, 30% to 35%, 35% to 40%, 40% to 45%, 45% to 50%, 50% to 60%, 60% to 70%, 70% to 80%, 80% n to 90%, and 90% to 99.9% by weight of the total composition.
To prepare a topical composition in lotion, cream or ointment form, the N-acetyl compound is first dissolved in water, ethanol, propylene glycol, diisopropyl adipate and/or another vehicle, and the solution thus obtained is mixed with a desired base or pharmaceutically acceptable vehicle to make lotion, cream or ointment. Concentrations of the N-acetyl compound are the same as described above for the solution form.
A topical composition of the instant invention may also be formulated in a gel or shampoo form. A typical gel composition is formulated by the addition of a gelling agent such as chitosan, methyl cellulose, ethyl cellulose, polyvinyl alcohol, polyquaterniums, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carbomer or ammoniated glycyrrhizinate to a solution comprising the N-acetyl compound. The preferred concentration of the gelling agent may range from 0.1 to 4 percent by weight of the total composition. In the preparation of shampoo, the N-acetyl compound is first dissolved in water or propylene glycol, and the solution thus obtained is mixed with a shampoo base. Concentrations of the N-acetyl compound used in gel or shampoo form are the same as described above.
To prepare a combination composition for synergetic effects, a cosmetic, pharmaceutical or other topical agent is incorporated into any one of the above compositions by dissolving or mixing the agent into the formulation.
Other forms of compositions for topical delivery of N-acetyl compound of the instant invention are readily prepared or formulated by those skilled in the art.
The following are illustrative examples of formulations according to this invention. Although the examples utilize only selected compounds and formulations, it should be understood that the following examples are illustrative and not limiting. Therefore, any of the aforementioned N-acetyl compounds may be substituted according to the teachings of this invention in the following examples.
EXAMPLE 1
A typical N-acetyl-aldosamine, N-acetylamino acid or the related acetyl compound in a cream composition may be formulated as follows. N-Acetyl-α-D-glucosamine 10 g was dissolved in 30 ml warm water, and the solution thus obtained was mixed uniformly with 60 g cream base or commercially available hydrophilic ointment. The white cream thus formulated contained 10% N-acetyl-glucosamine. N-Acetyl-glucosamine 1% or 5% cream was formulated in the same manner except that N-acetyl-α-D-glucosamine 1 g or 5 g was used, and was dissolved in 39 ml or 35 ml water.
EXAMPLE 2
N-Acetyl-D-mannosamine 1 g was dissolved in 20 ml warm water, and the solution thus obtained was mixed uniformly with 79 g cream base or commercially available hydrophilic ointment. The white cream thus formulated contained 1% N-acetyl-mannosamine.
EXAMPLE 3
N-Acetyl-L-glutamine 0.5 g was dissolved in 20 ml water, and the solution thus obtained was mixed uniformly with 79.5 g cream base or commercially available hydrophilic ointment. The white cream thus formulated contained 0.5% N-acetyl-L-glutamine.
EXAMPLE 4
N-Acetyl-DL-proline 2 g was dissolved in 20 ml warm water, and the solution thus obtained was mixed uniformly with 78 g cream base or commercially available hydrophilic ointment. The white cream thus formulated contained 2% N-acetyl-proline.
EXAMPLE 5
N-Acetyl-glycine 3 g was dissolved in 20 ml water, and the solution thus obtained was mixed uniformly with 77 g cream base or commercially available hydrophilic ointment. The white cream thus formulated contained 3% N-acetyl-glycine.
EXAMPLE 6
N-Acetyl-L-arginine 4 g was dissolved in 20 ml water, and the solution thus obtained was mixed uniformly with 76 g cream base or commercially available hydrophilic ointment. The white cream thus formulated contained 4% N-acetyl-arginine.
EXAMPLE 7
A typical N-acetyl-aldosamine, N-acetylamino acid or related N-acetyl compound in a solution composition may be formulated as follows. N-acetyl-α-D-glucosamine 0.5 g was dissolved in 99.5 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition thus prepared contained 0.5% N-acetyl-glucosamine. N-Acetyl-glucosamine 5% in solution form was formulated in the same manner except that 5 g instead of 0.5 g active ingredient was dissolved in 95 ml solution.
EXAMPLE 8
N-Acetyl-D-galactosamine 1 g was dissolved in 99 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition thus prepared contained 1% N-acetyl-galactosamine.
EXAMPLE 9
N-Acetyl-L-tyrosinamide 2 g was dissolved in 98 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition thus prepared contained 2% N-acetyl-tyrosinamide.
EXAMPLE 10
N-Acetyl-L-lysine 0.5 g was dissolved in 99.5 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition thus prepared contained 0.5% N-acetyl-lysine.
EXAMPLE 11
N-Acetyl-L-tyrosine 0.2 g was dissolved in 99.8 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition thus prepared contained 0.2% N-acetyl-tyrosine.
EXAMPLE 12
N-Acetyl-L-cysteine methyl ester 0.5 g was dissolved in 99.5 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition thus prepared contained 0.5% N-acetyl-cysteine methyl ester.
EXAMPLE 13
N-Acetyl-L-tyrosine ethyl ester 3 g was dissolved in 97 ml solution prepared from ethanol 80 ml and propylene glycol 20 ml. The composition thus prepared contained 3% N-acetyl-tyrosine ethyl ester.
EXAMPLE 14
N-acetyl-L-cysteine 2 g was dissolved in 98 ml solution prepared from water 80 ml and propylene glycol 20 ml. The composition thus prepared contained 2% N-acetyl-cysteine.
EXAMPLE 15
A typical combination composition comprising for example N-acetyamino acid ester and hydrocortisone 17-valerate for eczema and other inflammatory dermatoses may be formulated as follows.
N-Acetyl-L-tyrosine ethyl ester 3 g and hydrocortisone 17-valerate 0.4 g were dissolved in 20 ml warm propylene glycol, and the solution thus obtained was mixed uniformly with 76.6 g cream base or commercially available hydrophilic ointment. The white cream thus formulated had pH 5.1, and contained 3% N-acetyl-L-tyrosine ethyl ester and 0.4% hydrocortisone 17-valerate.
EXAMPLE 16
A typical combination composition comprising for example N-acetylaldosamine and an anti-itch agent may be formulated as follows.
N-Acetyl-α-D-glucosamine 2 g was dissolved in 10 ml water and the solution was mixed with diphenhydramine 2 g in 4 ml water containing 2 g gluconolactone. The above solution was mixed uniformly with 80 g cream base or commercially available hydrophilic ointment. The composition with pH 5.1 contained 2% N-acetyl-D-glucosamine and 2% diphenhydramine.
A male subject, age 66, having an itchy lesion of lichen simplex chronicus on his right lower leg topically applied the above cream to the lesion. A few minutes after the topical application, the itch disappeared completely and the skin remained free of itch for the following 12 hours.
4. Application and Treatment Using N-Acetyl-Aldosamines, N-Acetylamino Acids and Related N-Acetyl Compounds
The N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compositions of the present invention may be applied to any area of the skin, hair, or nails. Exemplary areas of application include the hands, arms, neck, legs, feet, trunk, hair shaft, nails, including the nail plate and nail cuticle, and on and around the face. Exemplary areas of facial application include the nose, forehead, and areas around the eyes. The compositions may be applied with or without occlusion. Any suitable occlusive device may be used. In addition, it is within the knowledge of the skilled artisan how best to apply such occlusive devices to achieve the desired result.
The compositions of the present invention may be applied to these areas with varying frequency and for varying duration. In this regard, the skilled artisan will appreciate how to alter the frequency and duration of application to achieve the desired effect. For example, the compositions of the instant invention can be applied at varying frequencies including on a daily basis, 1 or more times daily, or 1 or more times weekly. When being applied on a daily basis, the instant invention can be applied 1, 2, 3 or more times a day. When being applied on a weekly basis the instant invention can be applied 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more times a week. The duration of treatment with the compositions of the instant invention can also vary. For example, the compositions may be applied for 1, 2, 3, 4, 5, 6 or more weeks; or for 1, 2, 3, 4, 5, 6 or more months. The duration of treatment may also be continuous. Again, the skilled artisan will appreciate the interaction between frequency and duration of use in order to achieve and/or maintain the desired effect.
In addition, the skilled artisan will appreciate how to vary concentrations of the instant invention in conjunction with the frequency and duration of use to achieve the desired effect. For example, a composition of higher concentration might be applied with less frequency or for a shorter duration. In contrast, a composition of a lower concentration might be applied more frequently or for a longer duration.
TEST RESULTS A Method of Measurement
In one of the studies related to skin changes associated with aging, skin thickness was measured by micrometer calipers as follows: The skin was grasped with a 2×6 cm metal hinge, the internal faces of the hinge were coated with emery cloth to prevent slippage, and manually squeezed to threshold subject discomfort. Combined thickness of two whole-skin layers including thickness of the two hinge leaves was measured with micrometer calipers. Thickness of the two hinge leaves was subtracted to determine the actual thickness of two whole-skin layers. Triplicate measurements on treated site were done and an average number was used for calculation of the skin thickness.
1. Xerosis and Dry Skin
A male subject, age 66, who had xerosis and dry skin on lower legs topically applied twice daily 5% N-acetyl-glucosamine cream for one week. After a few days of topical treatment, the skin became less rough and scaly, and felt smooth. The dry skin returned to normal-looking skin after one week of topical application. This result indicated that N-acetyl-glucosamine was therapeutically effective for topical treatment of xerosis and dry skin.
2. Acne
A female subject, age 27, who had adolescent acne with multiple papules and pustules on her face applied topically twice daily 5% N-acetyl-glucosamine solution. After a few days of treatment, most lesions became less inflamed and gradually eradicated. This result indicated that N-acetyl-glucosamine was therapeutically effective for topical treatment of acne.
3. Effect of an N-acetyl Compound on Skin
In order to determine biological effects of a topically applied N-acetyl compound of the instant invention, seven women and one man of ages ranging from 58 to 81 years participated in this study. Topical formulation for the study was N-acetyl-L-cysteine 2% in a solution prepared from water 80 ml and propylene glycol 20 ml.
Test sites were 1 cm square sites on extensor surface of forearm, 5 cm from the antecubital crease, a grid pattern formed by Hayes Test Chambers on Hayes adhesive strips. Each test chamber, 1 cm square, contained a square piece of filter paper which was fully moistened with 0.033 ml test solution.
Test chambers were impressed on the skin to leave outlines which were marked with Sanford Sharpie permanent marker. Sites were re-marked at each successive application of test solutions. Vehicle control sites were on the opposite forearm. Filter paper of each chamber was saturated with 0.033 ml solution and chambers were fixed in place with the Hayes adhesive tape that held the test and vehicle chambers. Chambers were removed twice weekly, and replaced with a new adhesive strip of chambers with filter paper moistened with test or vehicle solutions. The test was carried out for five weeks. Punch biopsy specimens, 3 mm or 4 mm in diameter, were secured at the end of the study, and specimens were processed and analyzed. Measurements of several tissue characteristics were also made.
Punch biopsy specimens obtained from test and control sites were placed immediately into the fixative, and processed for histochemical staining.
Epidermal thickness was measured with Micro Image Analysis System, and the mean thickness was expressed as area of epidermis/horizontal length. The thickness of papillary dermis (upper dermis) was also measured.
All the skin sites treated with N-acetyl-cysteine showed an average of 96% increase in thickness of epidermis over the control. In addition, all the test sites showed 47-227% increase in production of hyaluronic acid in papillary dermis over the control.
The above results indicated that N-acetyl compounds of the instant invention would be topically beneficial for treatment of various cosmetic or dermatologic indications including wrinkles and changes of skin, nail and hair associated with intrinsic and extrinsic aging.
4. Effect of N-acetyl-glucosamine on Skin
A female subject, age 74, applied topically twice daily 10% N-acetyl-glucosamine cream to her right forearm for three weeks. After three weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 37% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-glucosamine would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
5. Effect of N-acetyl-DL-homocysteine thiolactone on Skin
A male subject, age 76, applied topically twice daily 5% N-acetyl-DL-homocysteine thiolactone cream to his right forearm for three weeks. After three weeks his untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, his right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of his left forearm, his right forearm had increased 89% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-homocysteine thiolactone would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
6. Effect of N-acetyl-L-cysteine on Skin
A female subject, age 71, applied topically twice daily 5% N-acetyl-L-cysteine cream to her right forearm for three weeks. After three weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 14% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-cysteine would be therapeutically effective for topical treatment of wrinkles and changes of skin, nails or hair associated with aging.
7. Effect of N-acetyl-L-cysteine methyl ester on Skin
A female subject, age 59, applied topically twice daily 5% N-acetyl-L-cysteine methyl ester cream to her right forearm for three weeks. After three weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 13% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-cysteine methyl ester would be therapeutically effective for topical treatment of wrinkles and changes of skin, nails or hair associated with aging.
8. Effect of N-acetyl-L-cysteine methyl ester on Skin
A female subject, age 72, applied topically twice daily 10% N-acetyl-L-cysteine methyl ester cream to her left forearm for three weeks. After three weeks her untreated right forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her left forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her right forearm, her left forearm had increased 26% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-L-cystine methylester would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
9. Effect of N-acetyl-L-cysteine methyl ester on Skin
A male subject, age 76, applied topically twice daily 5% N-acetyl-L-cysteine methyl ester cream to his left forearm for three weeks. After three weeks his untreated right forearm was still loose, relatively thin and wrinkled when lifted. In contrast, his left forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of his right forearm, his left forearm had increased 87% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-cysteine methyl ester would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
10. Effect of N-acetyl-DL-homocysteine thiolactone on Skin
A female subject, age 59, applied topically twice daily 5% N-acetyl-DL-homocysteine thiolactone cream to her left forearm for three weeks. After three weeks her untreated right forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her left forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her right forearm, her left forearm had increased 21% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-homocysteine thiolactone would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
11. Effect of N-acetyl-DL-tryptophan on Skin
A female subject, age 71, applied topically twice daily 10% N-acetyl-DL-tryptophan cream to her left forearm for three weeks. After three weeks her untreated right forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her left forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her right forearm, her left forearm had increased 11% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-tryptophan would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
12. Effect of N-acetyl-L-tyrosine ethyl ester on Skin
A female subject, age 47, applied topically twice daily 10% N-acetyl-L-tyrosine ethyl ester cream to her left forearm for four weeks. After four weeks her untreated right forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her left forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her right forearm, her left forearm had increased 11% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-L-tyrosine ethyl ester would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
13. Effect of N-acetyl-DL-tryptophan on Skin
A female subject, age 56, applied topically twice daily 10% N-acetyl-DL-tryptophan cream to her right forearm for three weeks. After three weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 21% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-tryptophan would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
14. Effect of N-acetyl-L-arginine on Skin
A female subject, age 47, applied topically twice daily 10% N-acetyl-L-arginine cream to her right forearm for four weeks. After four weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 32% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-L-arginine would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
15. Effect of N-acetyl-DL-tryptophan on Skin
A female subject, age 66, applied topically twice daily 10% N-acetyl-DL-tryptophan cream to her left forearm for five weeks. After five weeks her untreated right forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her left forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her right forearm, her left forearm had increased 12% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-tryptophan would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
16. Effect of N-acetyl-L-tyrosine ethyl ester on Skin
A female subject, age 72, applied topically twice daily 10% N-acetyl-L-tyrosine ethyl ester cream to her right forearm for four weeks. After four weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 34% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-tyrosine ethyl ester would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
17. Effect of N-acetyl-L-arginine on Skin
A female subject, age 72, applied topically twice daily 10% N-acetyl-L-arginine cream to her left forearm for four weeks. After four weeks her untreated right forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her left forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her right forearm, her left forearm had increased 22% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-arginine would be therapeutically effective for topical treatment of wrinkles and changes of skin, nail or hair associated with aging.
18. Effect of Combination Composition on Skin
A female subject, age 72, applied topically twice daily a combination cream formulated from 10% each of N-acetyl-α-D-glucosamine and gluconolactone to her right forearm for three weeks. After three weeks her untreated left forearm was still loose, relatively thin and wrinkled when lifted. In contrast, her right forearm was more firm, smooth, plump and minimally wrinkled when lifted. While there was no change in skin thickness of her left forearm, her right forearm had increased 118% in skin thickness as measured by the micrometer calipers. This result indicated that N-acetyl-glucosamine in combination with other topical agents would be topically effective for various cosmetic and dermatologic indications including wrinkles and changes of skin, nail and hair associated with intrinsic and extrinsic aging.
19. Effect of N-acetylamino Acid on the Scalp
A typical composition suitable for topical use on hair, scalp, nail and skin comprising for example N-acetylamino acid may be formulated as follows. N-Acetyl-DL-proline 2 g was dissolved in 98 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition with pH 2.7 contained 2% N-acetyl-DL-proline. A male subject, age 66, having itchy scalp topically applied the above composition to itchy area of scalp. A few minutes after the topical application, scalp itch disappeared completely and the scalp remained free of itch for the next 24 hours.
20. Effect of Combination Composition (Anti-fungal Agent) on Nail or Scalp
A typical composition comprising for example N-acetylamino acid in combination with an anti-fungal agent for nail or scalp infections may be formulated as follows. N-Acetylglycine 2 g was dissolved in 98 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition thus prepared contained 2% N-acetylglycine, and was used as a nail or scalp conditioner. For nail or scalp infections, N-acetylglycine 2 g and clotrimazole 2 g were dissolved in 96 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition with pH 3.7 contained 2% N-acetylglycine and 2% clotrimazole, and were topically effective for nail or scalp infections.
21. N-acetylamino Shampoo Composition
A typical shampoo composition comprising for example N-acetylamino acid for hair, scalp or body wash may be formulated as follows. N-Acetyl-L-arginine 4 g was dissolved in 20 ml water, and the solution thus obtained was mixed uniformly with 76 g shampoo base. The shampoo composition with pH 6.6 contained 4% N-acetyl-L-arginine
22. Effect N-acetyl-L-lysine on an Oily Scalp
N-Acetyl-L-lysine 2 g was dissolved in a 98 ml solution prepared from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The composition with pH 6.5 contained 2% N-acetyl-L-lysine. A male subject, age 66, having an oily and pruritic scalp topically applied the above composition to the affected area of the scalp, and the area was dried with warm air to remove excess solvents. A few minutes after the topical application, the scalp itch disappeared completely and the scalp remained free of itch the next 12 hours.
23. Effect of N-acetyl-DL-proline on Pruritus
A male subject, age 77, with chronic Grover's Disease (Acantholytic Dermatosis) for approximately one year duration had complained about excruciating pruritus on skin lesions of inflammatory papules which did not respond well to conventional topical anti-inflammatory agents. The subject topically applied N-acetyl-DL-proline 5% in oil-in-water cream to the itchy lesions. A few minutes after the topical application, the severe itch disappeared completely and the lesions remained free of itch for the next 12 hours.
24. Effect of N-acetyl-D-galactosamine on Urticaria
A female subject, age 72, having acute urticaria due to unknown cause did not respond to conventional topical anti-itch medications. The subject topically applied N-acetyl-D-galactosamine 5% in solution to skin areas of the urticarial lesions. A few minutes after the topical application, the severe itch disappeared completely and the skin remained free of itch for the next 24 hours with concomitant disappearance of urticarial lesions.
25. Effect of N-acetyl-DL-proline on Itchy Skin and Dry Skin Lesions
A female subject, age 86, with chronic nummular eczema and pruritic dry skin topically applied N-acetyl-DL-proline 5% in solution to itchy skin areas of eczema and dry skin lesions. A few minutes after the topical application, the itch disappeared completely and the lesions remained free of itch for the next 48 hours.
26. Effect of N-acetyl-DL-proline on Itchy Skin
A male subject, age 76, having axillary itch due to use of a conventional antiperspirant topically applied N-acetyl-DL-proline 5% in solution to itchy underarm skin areas. Within a few minutes after the topical application, the itch disappeared completely and the skin remained free of itch for the next five days.
27. Effect of N-acetyl-L-glutamine on Pruritus
A male subject, age 77, with chronic Grover's Disease (Acantholytic Dermatosis) for approximately one year duration had complained about excruciating pruritus on skin lesions of inflammatory papules which did not respond well to conventional topical anti-inflammatory agents. The subject topically applied N-acetyl-L-glutamine 5% in a solution prepared from water 4 parts, ethanol 4 parts and propylene glycol 2 parts by volume. A few minutes after the topical application, the severe itch disappeared completely and the lesions remained free of itch for the next 24 hours.
28. Effect of N-acetyl-α-D-glucosamine on Pruritus
A male subject, age 77, with chronic Grover's Disease (Ancantholytic Dermatosis) for approximately one year duration had complained about excruciating pruritus on skin lesions of inflammatory papules which did not respond well to conventional topical anti-inflammatory agents. The subject topically applied N-acetyl-α-D-glucosamine 5% in a solution prepared from water 4 parts, ethanol 4 parts and propylene glycol 2 parts by volume. A few minutes after the topical application, the severe itch disappeared completely and the lesions remained free of itch for the next 24 hours.
The invention described herein may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The specific embodiments previously described are therefore to be considered as illustrative of, and not limiting, the scope of the invention. Additionally, the disclosure of all publications cited above are expressly incorporated herein by reference in their entireties to the same extent as if each were incorporated by reference individually.

Claims (39)

We claim:
1. A composition comprising (A) a pharmaceutically acceptable vehicle for topical treatment of cosmetic conditions or dermatological disorders and (B) a therapeutically effective amount of at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof,
wherein said N-acetyl aldosamine has the formula:
Figure USRE044302-20130618-C00003
wherein n is an integer; R1 is selected from the group consisting of CHO, CONH2, and COOR3; R2 is selected from the group consisting of H, I, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated, straight or branched chain or cyclic form having 1 to 19 carbon atoms; R3 is selected from the group consisting of H and an alkyl, aralkyl, or aryl group having from 1 to 9 carbon atoms,
wherein said N-acetylamino acid or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester form thereof is at least one member selected from the group consisting of N-acetyl-glycine, N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl-serine, N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-methionine, N-acetyl-aspartic acid, N-acetyl-asparagine, N-acetyl-glutamine, N-acetyl-arginine, N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine, N-acetyl-tryptophan, N-acetyl-β-alanine, N-acetyl-taurine, N-acetyl-r-aminobutanoic acid, N-acetyl-hydroxyproline, N-acetyl-canavanine, N-acetyl-hydroxylysine, N-acetyl-cycloserine, N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline, N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline, N-acetyl-ethionine, N-acetyl-methoxinine, N-acetyl-β-aminoisobutanoic acid, N-acetyl-homocysteine, N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine, N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine (N-acetyl-serotonin), N-acetyltryptamine, N-acetyl-ornithine, N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa, N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine, N-acetyl-3,5,3′-triiodothyronine, N-acetyl-thyroxine, N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine, N-acetyl-homocystine, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof, and N-acetyl-glutamic acid and isomeric or nonisomeric, free acid, lactone, amide, or ester forms thereof.
2. The composition of claim 1, wherein said N-acetyl aldosamine or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester form thereof is at least one member selected from the group consisting of N-acetyl-glycerosamine, N-acetyl-erythrosamine, N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine, N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine, N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine, N-acetyl-talosamine, N-acetyl-glucoheptosamine, N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine, N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine, N-acetylneuramin Lactose, N-acetyl-glyceraminic acid, N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid, N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid, N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid, N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid, N-acetyl-glucosaminic acid, N-acetyl-mannosaminic acid, N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid, N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid, N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid, N-acetyl-heptomannosaminic acid, N-acetyl-N-acetylneuraminic acid, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof.
3. The composition of claim 1, wherein said cosmetic conditions and dermatological disorders are selected from the group consisting of disturbed keratinization, defective syntheses of dermal components, and changes associated with aging of skin, nail and hair, conditions and disorders which include dryness or loose of skin, nail and hair, xerosis, ichthyosis, palmar hyerperkeratoses, plantar hyperkeratoses, uneven and rough surfaces of skin, nail and hair, dandruff, Darier's disease, lichen simplex chronicus, keratoses, acne, pseudofolliculitis barbae, eczema, psoriasis, pruritus, warts, herpes, age spots, lentigines, melasmas, blemished skin, hyperkeratoses, hyperpigmented skin, abnormal or diminished syntheses of collagen, glycosaminoglycans, proteoglycans and elastin as well as diminished levels of such components in the dermis, stretch marks, skin lines, fine lines, wrinkles, thinning of skin, nail plate and hair, skin thickening due to elastosis of photoaging, loss or reduction of skin, nail and hair resiliency, elasticity and recoilability, lack of skin, nail and hair lubricants and luster, dull and older-looking skin, nails and hair, and fragility and splitting of nails and hair.
4. A composition comprising:
(A) a pharmaceutically acceptable vehicle for topical treatment of cosmetic conditions or dermatological disorders,
(B) a therapeutically effective amount of at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof, wherein said N-acetyl aldosamine has the formula:
Figure USRE044302-20130618-C00004
wherein n is an integer; R1 is selected from the group consisting of CHO, CONH2, and COOR3; R2 is selected from the group consisting of H, I, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated, straight or branched chain or cyclic form having 1 to 19 carbon atoms; R3 is selected from the group consisting of H and an alkyl, aralkyl, or aryl group having from 1 to 9 carbon atoms,
wherein said N-acetylamino acid has the formula:
Figure USRE044302-20130618-C00005
wherein R1 is H or an alkyl or aralkyl group having 1 to 14 carbon atoms; n is an integer; R2 is OH, NH2 or OR3; and R3 is an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms which may be saturated or unsaturated, straight or branched chain or cyclic form; H attached to a carbon atom may be substituted by I, F, Cl, Br or an alkoxyl group having 1 to 9 carbons; and R1 may carry OH, SH, SCH3, COOH, NH2, CONH2, guanidine or heterocyclic group,
and wherein said N-acetylamino acid is not N-acetylcysteine or a derivative thereof, and
(C) a cosmetic, pharmaceutical or other topical agent.
5. The composition of claim 4, wherein said N-acetyl aldosamine or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester form thereof is at least one member selected from the group consisting of N-acetyl-glycerosamine, N-acetyl-erythrosamine, N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine, N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine, N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine, N-acetyl-talosamine, N-acetyl-glucoheptosamine, N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine, N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine, N-acetylneuramin Lactose, N-acetyl-glyceraminic acid, N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid, N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid, N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid, N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid, N-acetyl-glucosaminic acid; N-acetyl-mannosaminic acid, N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid, N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid, N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid, N-acetyl-heptomannosaminic acid, N-acetyl-N-acetylneuraminic acid, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof.
6. The composition of claim 4 wherein said N-acetylamino acid or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester form thereof is at least one member selected from the group consisting of N-acetyl-glycine, N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl-serine, N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-methionine, N-acetyl-aspartic acid, N-acetyl-asparagine, N-acetyl-glutamic acid, N-acetyl-glutamine, N-acetyl-arginine, N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine, N-acetyl-tryptophan, N-acetyl-proline, N-acetyl-β-alanine, N-acetyl-taurine, N-acetyl-r-aminobutanoic acid, N-acetyl-hydroxyproline, N-acetyl-canavanine, N-acetyl-hydroxylysine, N-acetyl-cycloserine, N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline, N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline, N-acetyl-ethionine, N-acetyl-methoxinine, N-acetyl-β-aminoisobutanoic acid, N-acetyl-homocysteine, N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine, N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine (N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine, N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa, N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine, N-acetyl-3,5,3′-triiodothyronine, N-acetyl-thyroxine, N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine, N-acetyl-homocystine, and or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof.
7. The composition of claim 4, wherein said cosmetic conditions and dermatological disorders are selected from the group consisting of disturbed keratinization, defective syntheses of dermal components, and changes associated with aging of skin, nail and hair, conditions and disorders which include dryness or loose of skin, nail and hair, xerosis, ichthyosis, palmar hyerperkeratoses, plantar hyperkeratoses, uneven and rough surfaces of skin, nail and hair, dandruff, Darier's disease, lichen simplex chronicus, keratoses, acne, pseudofolliculitis barbae, eczema, psoriasis, pruritus, warts, herpes, age spots, lentigines, melasmas, blemished skin, hyperkeratoses, hyperpigmented skin, abnormal or diminished syntheses of collagen, glycosaminoglycans, proteoglycans and elastin as well as diminished levels of such components in the dermis, stretch marks, skin lines, fine lines, wrinkles, thinning of skin, nail plate and hair, skin thickening due to elastosis of photoaging, loss or reduction of skin, nail and hair resiliency, elasticity and recoilability, lack of skin, nail and hair lubricants and luster, dull and older-looking skin, nails and hair, and fragility and splitting of nails and hair.
8. The composition of claim 4, wherein said cosmetic, pharmaceutical, or other topical agent is selected from the group consisting of agents that improve or eradicate age spots, keratoses and wrinkles, local analgesics and anesthetics, antiacne agents, antibacterials, antiyeast agents, antifungal agents, antiviral agents, antidandruff agents, antidermatitis agents, antihistamine agents, antipruritic agents, antiemetics, antimotion sickness agents, antiinflammatory agents, antihyperkeratolytic agents, antiperspirants, antipsoriatic agents, antiseborrheic agents, hair conditioners and hair treatment agents, antiaging and antiwrinkle agents, sunblock and sunscreen agents, skin lightening agents, depigmenting agents, vitamins, corticosteroids, tanning agents, hormones, retinoids, and topical cardiovascular agents.
9. The composition of claim 8, wherein said cosmetic, pharmaceutical, or other topical agent is selected from the group consisting of clotrimazole, ketoconazole, miconazole, griseofulvin, econazole, metronidazole, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin, meclocycline, hydroquinone, hydroquinone monoether, minocycline, naproxen, ibuprofen, theophylline, cromolyn, albuterol, retinol, retinyl acetate, retinyl palmitate, retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone dipropionate, triamcinolone acetonide, fluocinonide, clobetasol propionate, benzoyl peroxide, crotamiton, propranolol, promethazine, salicylic acid, vitamin E and vitamin E acetate.
10. A composition comprising (A) a pharmaceutically acceptable vehicle for topical treatment of cosmetic conditions or dermatological disorders and (B) at least 1% by total weight of the composition of at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof,
wherein said N-acetyl aldosamine has the formula:
Figure USRE044302-20130618-C00006
wherein n is an integer; R1 is selected from the group consisting of CHO, CONH2, and COOR3; R2 is selected from the group consisting of H, I, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated, straight or branched chain or cyclic form having 1 to 19 carbon atoms; R3 is selected from the group consisting of H and an alkyl, aralkyl, or aryl group having from 1 to 9 carbon atoms,
wherein said N-acetylamino acid or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester form thereof is at least one member selected from the group consisting of N-acetyl-glycine, N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl-serine, N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-methionine, N-acetyl-aspartic acid, N-acetyl-asparagine, N-acetyl-glutamine, N-acetyl-arginine, N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine, N-acetyl-tryptophan, N-acetyl-proline, N-acetyl-β-alanine, N-acetyl-taurine, N-acetyl-r-aminobutanoic acid, N-acetyl-hydroxyproline, N-acetyl-canavanine, N-acetyl-hydroxylysine, N-acetyl-cycloserine, N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline, N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline, N-acetyl-ethionine, N-acetyl-methoxinine, N-acetyl-β-aminoisobutanoic acid, N-acetyl-homocysteine, N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine, N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine (N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine, N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa, N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine, N-acetyl-3,5,3′-triiodothyronine, N-acetyl-thyroxine, N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine, N-acetyl-homocystine, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof, and N-acetyl glutamic acid and isomeric or nonisomeric, free acid, lactone, amide, or ester forms thereof.
11. A composition comprising:
(A) a pharmaceutically acceptable vehicle for topical treatment of cosmetic conditions or dermatological disorders,
(B) at least 1% by total weight of the composition of at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof,
wherein said N-acetyl aldosamine has the formula:
Figure USRE044302-20130618-C00007
wherein n is an integer; R1 is selected from the group consisting of CHO, CONH2, and COOR3; R2 is selected from the group consisting of H, I, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated, straight or branched chain or cyclic form having 1 to 19 carbon atoms; R3 is selected from the group consisting of H and an alkyl, aralkyl, or aryl group having from 1 to 9 carbon atoms,
wherein said N-acetylamino acid is N-acetyl-proline or has the formula:
Figure USRE044302-20130618-C00008
wherein R1 is H or an alkyl or aralkyl group having 1 to 14 carbon atoms; n is an integer; R2 is OH, NH2 or OR3; and R3 is an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms which may be saturated or unsaturated, straight or branched chain or cyclic form; H attached to a carbon atom may be substituted by I, F, Cl, Br or an alkoxyl group having 1 to 9 carbons; and R1 may carry OH, SH, SCH3, COOH, NH2, CONH2, guanidine or heterocyclic group,
and wherein said N-acetylamino acid is not N-acetylcysteine or a derivative thereof, and
(C) a cosmetic, pharmaceutical or other topical agent.
12. A method for treating cosmetic conditions and dermatological disorders comprising topically applying a composition comprising (A) a pharmaceutically acceptable vehicle for topical treatment of cosmetic conditions or dermatological disorders and (B) a therapeutically effective amount of a composition comprising at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof,
wherein said N-acetyl aldosamine has the formula:
Figure USRE044302-20130618-C00009
wherein n is an integer; R1 is selected from the group consisting of CHO, CONH2, and COOR3; R2 is selected from the group consisting of H, I, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated, straight or branched chain or cyclic form having 1 to 19 carbon atoms; R3 is selected from the group consisting of H and an alkyl, aralkyl or aryl group having from 1 to 9 carbon atoms, and
wherein said N-acetylamino acid or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester form thereof is at least one member selected from the group consisting of N-acetyl-glycine, N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl-serine, N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-cysteine, N-acetyl-methionine, N-acetyl-aspartic acid, N-acetyl-asparagine, N-acetyl-glutamine, N-acetyl-arginine, N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine, N-acetyl-tryptophan, N-acetyl-proline, N-acetyl-β-alanine, N-acetyl-taurine, N-acetyl-r-aminobutanoic acid, N-acetyl-hydroxyproline, N-acetyl-canavanine, N-acetyl-hydroxylysine, N-acetyl-cycloserine, N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline, N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline, N-acetyl-ethionine, N-acetyl-methoxinine, N-acetyl-β-aminoisobutanoic acid, N-acetyl-homocysteine, N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine, N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine (N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine, N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa, N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine, N-acetyl-3,5,3′-triiodothyronine, N-acetyl-thyroxine, N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine, N-acetyl-homocystine, and isomeric or nonisomeric, free acid, salt lactone, amide, or ester forms thereof, and N-acetyl-glutamic acid and isomeric or nonisomeric, free acid, lactone, amide, or ester forms thereof.
13. The method of claim 12, wherein said N-acetyl aldosamine or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester form thereof is at least one member selected from the group consisting of N-acetyl-glycerosamine, N-acetyl-erythrosamine, N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine, N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine, N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine, N-acetyl-talosamine, N-acetyl-glucoheptosamine, N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine, N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine, N-acetylneuramin Lactose, N-acetyl-glyceraminic acid, N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid, N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid, N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid, N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid, N-acetyl-glucosaminic acid, N-acetyl-mannosaminic acid, N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid, N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid, N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid, N-acetyl-heptomannosaminic acid, N-acetyl-N-acetylneuraminic acid, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof.
14. The method of claim 12, wherein said cosmetic conditions and dermatological disorders are selected from the group consisting of disturbed keratinization, defective syntheses of dermal components, and changes associated with aging of skin, nail and hair, conditions and disorders which include dryness or loose of skin, nail and hair, xerosis, ichthyosis, palmar hyerperkeratoses, plantar hyperkeratoses, uneven and rough surfaces of skin, nail and hair, dandruff, Darier's disease, lichen simplex chronicus, keratoses, acne, pseudofolliculitis barbae, eczema, psoriasis, pruritus, warts, herpes, age spots, lentigines, melasmas, blemished skin, hyperkeratoses, hyperpigmented skin, abnormal or diminished syntheses of collagen, glycosaminoglycans, proteoglycans and elastin as well as diminished levels of such components in the dermis, stretch marks, skin lines, fine lines, wrinkles, thinning of skin, nail plate and hair, skin thickening due to elastosis of photoaging, loss or reduction of skin, nail and hair resiliency, elasticity and recoilability, lack of skin, nail and hair lubricants and luster, dull and older-looking skin, nails and hair, and fragility and splitting of nails and hair.
15. A method for treating cosmetic conditions and dermatological disorders comprising topically applying a composition comprising:
(A) a pharmaceutically acceptable vehicle for topical treatment of cosmetic conditions or dermatological disorders,
(B) a therapeutically effective amount of at least one compound selected from the group consisting of N-acetyl aldosamines, N-acetylamino acids, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof,
wherein said N-acetyl aldosamine has the formula:
Figure USRE044302-20130618-C00010
wherein n is an integer; R1 is selected from the group consisting of CHO, CONH2, and COOR3; R2 is selected from the group consisting of H, I, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated, straight or branched chain or cyclic form having 1 to 19 carbon atoms; R2 is selected from the group consisting of H and an alkyl, aralkyl, or aryl group having from 1 to 9 carbon atoms,
wherein said N-acetylamino acid is N-acetyl-proline or has the formula:
Figure USRE044302-20130618-C00011
wherein R1 is H or an alkyl or aralkyl group having 1 to 14 carbon atoms; n is an integer; R2 is OH, NH2 or OR3; and R3 is an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms which may be saturated or unsaturated, straight or branched chain or cyclic form; H attached to a carbon atom may be substituted by I, F, Cl, Br or an alkoxyl group having 1 to 9 carbons; and R1 may carry OH, SH, SCH3, COOH, NH2, CONH2, guanidine or heterocyclic group, and wherein said N-acetylamino acid is not N-acetylcysteine or a derivative thereof, and
(C) a cosmetic, pharmaceutical or other topical agent.
16. The method of claim 15, wherein said N-acetyl aldosamine or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester form thereof is at least one member selected from the group consisting of N-acetyl-glycerosamine,N-acetyl-erythrosamine, N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine, N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine, N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine, N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine, N-acetyl-talosamine, N-acetyl-glucoheptosamine, N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine, N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine, N-acetylneuramin Lactose, N-acetyl-glyceraminic acid, N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid, N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid, N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid, N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid, N-acetyl-glucosaminic acid, N-acetyl-mannosaminic acid, N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid, N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid, N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid, N-acetyl-heptomannosaminic acid, N-acetyl-N-acetylneuraminic acid, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof.
17. The method of claim 15, wherein said N-acetylamino acid or isomeric or nonisomeric, free acid, salt, lactone, amide, or ester form thereof is at least one member selected from the group consisting of N-acetyl-glycine, N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl-serine, N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-methionine, N-acetyl-aspartic acid, N-acetyl-asparagine, N-acetyl-glutamic acid, N-acetyl-glutamine, N-acetyl-arginine, N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine, N-acetyl-tryptophan, N-acetyl-proline, N-acetyl-β-alanine, N-acetyl-taurine, N-acetyl-r-aminobutanoic acid, N-acetyl-hydroxyproline, N-acetyl-canavanine, N-acetyl-hydroxylysine, N-acetyl-cycloserine, N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline, N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline, N-acetyl-ethionine, N-acetyl-methoxinine, N-acetyl-β-aminoisobutanoic acid, N-acetyl-homocysteine, N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine, N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine (N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine, N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa, N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine, N-acetyl-3,5,3′-triiodothyronine, N-acetyl-thyroxine, N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine, N-acetyl-homocystine, and isomeric or nonisomeric, free acid, salt, lactone, amide, or ester forms thereof.
18. The method of claim 15, wherein said cosmetic conditions and dermatological disorders are selected from the groups consisting of disturbed keratinization, defective syntheses of dermal components, and changes associated with aging of skin, nail and hair, conditions and disorders which include dryness or loose of skin, nail and hair, xerosis, ichthyosis, palmar hyerperkeratoses, plantar hyperkeratoses, uneven and rough surfaces of skin, nail and hair, dandruff, Darier's disease, lichen simplex chronicus, keratoses, acne, pseudofolliculitis barbae, eczema, psoriasis, pruritus, warts, herpes, age spots, lentigines, melasmas, blemished skin, hyperkeratoses, hyperpigmented skin, abnormal or diminished syntheses of collagen, glycosaminoglycans, proteoglycans and elastin as well as diminished levels of such components in the dermis, stretch marks, skin lines, fine lines, wrinkles, thinning of skin, nail plate and hair, skin thickening due to elastosis of photoaging, loss or reduction of skin, nail and hair resiliency, elasticity and recoilability, lack of skin, nail and hair lubricants and luster, dull and older-looking skin, nails and hair, and fragility and splitting of nails and hair.
19. The method of claim 15, wherein said cosmetic, pharmaceutical, or other topical agent is selected from the group consisting of agents that improve or eradicate age spots, keratoses and wrinkles, local analgesics and anesthetics, antiacne agents, antibacterials, antiyeast agents, antifungal agents, antiviral agents, antidandruff agents, antidermatitis agents, antihistamine agents, antipruritic agents, antiemetics, antimotion sickness agents, antiinflammatory agents, antihyperkeratolytic agents, antiperspirants, antipsoriatic agents, antiseborrheic agents, hair conditioners and hair treatment agents, antiaging and antiwrinkle agents, sunblock and sunscreen agents, skin lightening agents, depigmenting agents, vitamins, corticosteroids, tanning agents, hormones, retinoids, and topical cardiovascular agents.
20. The method of claim 19, wherein said cosmetic, pharmaceutical, or other topical agent is selected from the group consisting of clotrimazole, ketoconazole, miconazole, griseofulvin, econazole, metronidazole, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin, meclocycline, hydroquinone, hydroquinone monoether, minocycline, naproxen, ibuprofen, theophylline, cromolyn, albuterol, retinol, retinyl acetate, retinyl palmitate, retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone dipropionate, triamcinolone acetonide, fluocinonide, clobetasol propionate, benzoyl peroxide, crotamiton, propranolol, promethazine, salicylic acid, vitamin E, and vitamin E acetate.
21. A method for treating dermal conditions comprising topically applying a water-containing composition comprising (A) a cosmetically acceptable vehicle and (B) a therapeutically effective amount of N-acetyl-glucosamine, wherein the composition does not contain glucuronic acid, or vitamin E,
wherein the conditions are selected from the group consisting of defective syntheses of dermal components, conditions and disorders selected from abnormal or diminished syntheses of collagen and elastin, diminished levels of collagen and elastin, and skin thickening due to elastosis of photoaging.
22. The method of claim 21, wherein the condition is diminished levels of collagen.
23. The method of claim 21, wherein the condition is abnormal or diminished synthesis of collagen.
24. The method of claim 21, wherein the condition is diminished levels of elastin.
25. The method of claim 21, wherein the condition is abnormal or diminished synthesis of elastin.
26. The method of claim 21, wherein the composition further comprises other topical agents selected from the group consisting of agents that improve or eradicate age spots, keratoses, local analgesics and anesthetics, antiacne agents, antiyeast agents, antidermatitis agents, antihistamine agents, antipruritic agents, antiemetics, antimotion sickness agents, antiinflammatory agents, antihyperkeratotic agents, antiperspirants, antipsoriatic agents, antiseborrheic agents, hair conditioners and hair treatment agents, antiaging and antiwrinkle agents, sunblock and sunscreen agents, skin lightening agents, depigmenting agents, vitamins, corticosteroids, tanning agents, hormones, retinoids, and topical cardiovascular agents.
27. The method of claim 26, wherein the topical agent is selected from the group consisting of hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, hydroquinone, hydroquinone monoether, naproxen, ibuprofen, theophylline, cromolyn, albuterol, retinol, retinyl acetate, retinyl palmitate, retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone dipropionate, triamcinolone acetonide, fluocinonide, clobetasol propionate, benzoyl peroxide, crotamiton, propranolol, promethazine, and salicylic acid.
28. The method of claim 26, wherein the topical agent is a vitamin.
29. The method of claim 28, wherein the vitamin is vitamin B3, niacinamide.
30. The method of claim 29, wherein the composition comprises N-acetyl-glucosamine and niacinamide, and the conditions are selected from the group consisting of diminished levels of collagen and elastin, and skin thickening due to elastosis of photoaging.
31. The method of claim 30, wherein the condition is diminished levels of collagen.
32. A method for treating dermal conditions comprising topically applying a water-containing composition consisting essentially of (A) a cosmetically acceptable vehicle; (B) a therapeutically effective amount of N-acetyl-glucosamine; and optionally (C) a topical agent,
wherein the conditions are selected from the group consisting of defective syntheses of dermal components, conditions and disorders selected from abnormal or diminished syntheses of collagen and elastin, diminished levels of collagen and elastin, and skin thickening due to elastosis of photoaging.
33. The method as claimed in claim 32, wherein the topical agent is selected from the group consisting of local analgesics and anesthetics, antiacne agents, antiyeast agents, antidermatitis agents, antihistamine agents, antipruritic agents, antiemetics, antimotion sickness agents, antiinflammatory agents, antihyperkeratotic agents, antiperspirants, antipsoriatic agents, antiseborrheic agents, antiaging and antiwrinkle agents, sunblock and sunscreen agents, skin lightening agents, depigmenting agents, vitamins, corticosteroids, tanning agents, hormones, retinoids, and topical cardiovascular agents.
34. The method of claim 33, wherein the topical agent is selected from the group consisting of hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, hydroquinone, hydroquinone monoether, naproxen, ibuprofen, theophylline, cromolyn, albuterol, retinol, retinyl acetate, retinyl palmitate, retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone dipropionate, triamcinolone acetonide, fluocinonide, clobetasol propionate, benzoyl peroxide, crotamiton, propranolol, promethazine, and salicylic acid.
35. The method of claim 33, wherein the topical agent is a vitamin.
36. The method of claim 35, wherein the vitamin is vitamin B3, niacinamide.
37. The method of claim 36, wherein the composition comprises N-acetyl-glucosamine and niacinamide, and the conditions are selected from the group consisting of diminished levels of collagen and elastin, and skin thickening due to elastosis of photoaging.
38. The method of claim 37, wherein the condition is diminished levels of collagen.
39. The method of claim 32, wherein the topical agent is one or more topical agents selected from the group consisting of sunblock and sunscreen agents, and vitamins.
US12/722,170 1999-01-08 2010-03-11 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use Expired - Lifetime USRE44302E1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US12/722,170 USRE44302E1 (en) 1999-01-08 2010-03-11 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
US13/046,047 USRE44017E1 (en) 1999-01-08 2011-03-11 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US09/227,213 US6159485A (en) 1999-01-08 1999-01-08 N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use
US11/590,898 USRE41339E1 (en) 1999-01-08 2006-11-01 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
US12/536,209 USRE42902E1 (en) 1999-01-08 2009-08-05 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
US12/722,170 USRE44302E1 (en) 1999-01-08 2010-03-11 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
US09/227,213 Reissue US6159485A (en) 1999-01-08 1999-01-08 N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use
US12/536,209 Continuation USRE42902E1 (en) 1999-01-08 2009-08-05 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/227,213 Continuation US6159485A (en) 1999-01-08 1999-01-08 N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use

Publications (1)

Publication Number Publication Date
USRE44302E1 true USRE44302E1 (en) 2013-06-18

Family

ID=22852222

Family Applications (7)

Application Number Title Priority Date Filing Date
US09/227,213 Ceased US6159485A (en) 1999-01-08 1999-01-08 N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use
US09/560,901 Ceased US6524593B1 (en) 1999-01-08 2000-04-28 N-acetyl aldosamines and related N-acetyl compounds, and their topical use
US11/590,898 Expired - Lifetime USRE41339E1 (en) 1999-01-08 2006-11-01 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
US11/590,897 Expired - Lifetime USRE41278E1 (en) 1999-01-08 2006-11-01 N-acetyl aldosamines and related N-acetyl compounds, and their topical use
US12/536,209 Expired - Lifetime USRE42902E1 (en) 1999-01-08 2009-08-05 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
US12/722,170 Expired - Lifetime USRE44302E1 (en) 1999-01-08 2010-03-11 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
US13/046,047 Expired - Lifetime USRE44017E1 (en) 1999-01-08 2011-03-11 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use

Family Applications Before (5)

Application Number Title Priority Date Filing Date
US09/227,213 Ceased US6159485A (en) 1999-01-08 1999-01-08 N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use
US09/560,901 Ceased US6524593B1 (en) 1999-01-08 2000-04-28 N-acetyl aldosamines and related N-acetyl compounds, and their topical use
US11/590,898 Expired - Lifetime USRE41339E1 (en) 1999-01-08 2006-11-01 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
US11/590,897 Expired - Lifetime USRE41278E1 (en) 1999-01-08 2006-11-01 N-acetyl aldosamines and related N-acetyl compounds, and their topical use
US12/536,209 Expired - Lifetime USRE42902E1 (en) 1999-01-08 2009-08-05 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use

Family Applications After (1)

Application Number Title Priority Date Filing Date
US13/046,047 Expired - Lifetime USRE44017E1 (en) 1999-01-08 2011-03-11 N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use

Country Status (12)

Country Link
US (7) US6159485A (en)
EP (5) EP2311452B2 (en)
JP (2) JP2002534369A (en)
CN (1) CN1336817A (en)
AU (1) AU775209B2 (en)
BR (1) BR0007430A (en)
CA (3) CA2358457C (en)
DE (2) DE60041934D1 (en)
ES (3) ES2477556T3 (en)
HK (1) HK1156853A1 (en)
MX (1) MXPA01006917A (en)
WO (1) WO2000040217A1 (en)

Families Citing this family (183)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2761600B1 (en) * 1998-06-19 2000-03-31 Oreal FOAMING COMPOSITION FOR THE WASHING AND TREATMENT OF HAIR AND / OR SCALP BASED ON AN ACTIVE INGREDIENT, AN ANIONIC SURFACTANT, AN AMPHOTERIC SURFACTANT AND A PROPENETANT
US6808716B2 (en) * 1999-01-08 2004-10-26 Ruey J. Yu N-acetylamino acids, related N-acetyl compounds and their topical use
US6159485A (en) 1999-01-08 2000-12-12 Yugenic Limited Partnership N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use
US6413525B1 (en) 1999-05-06 2002-07-02 Color Access, Inc. Methods of exfoliation using N-acetyl glucosamine
FR2794974B1 (en) * 1999-06-16 2001-08-17 Exsymol Sa COSMETIC COMPOSITION FOR SLIMMING BASED ON L-ARGININE, AN ANALOG OF L-ARGININE OR A DERIVATIVE THEREOF, APPLICABLE TOPICALLY
US6242491B1 (en) 1999-06-25 2001-06-05 Rima Kaddurah-Daouk Use of creatine or creatine compounds for skin preservation
US7083781B2 (en) 1999-08-19 2006-08-01 Lavipharm S.A. Film forming polymers, methods of use, and devices and applications thereof
WO2002006225A1 (en) * 2000-07-19 2002-01-24 Kyowa Hakko Kogyo Co., Ltd. Preventives or remedies for atopic dermatitis
JP2002128651A (en) * 2000-10-25 2002-05-09 Kose Corp Photoaging inhibitor and skin care preparation characterized by comprising the same
DK1343492T3 (en) * 2000-11-22 2006-03-06 Rxkinetix Inc Treatment of mucositis
JP2002193782A (en) * 2000-12-22 2002-07-10 Shiyuu Uemura Keshohin:Kk Skin cosmetic
CA2433714C (en) * 2001-01-05 2009-03-03 Kyowa Hakko Kogyo Co., Ltd. Arthritis preventing or treating agent
US20040131574A1 (en) * 2001-02-07 2004-07-08 Bergeron Raymond J Method and composition for the control of hair growth
CN1168453C (en) * 2001-02-28 2004-09-29 中国人民解放军第三军医大学 Application of N-acetyl-D-aminoglucose in preparing medicine to prevent and treat motion sickness
NL1017487C2 (en) * 2001-03-02 2002-09-06 Caral B V I O Preparation with polydimethylsiloxane for disorders of nails, cartilage, bones, joints, muscles and tendons.
US20020182237A1 (en) * 2001-03-22 2002-12-05 The Procter & Gamble Company Skin care compositions containing a sugar amine
DE10114561A1 (en) 2001-03-24 2002-09-26 Wella Ag Creatine, creatinine and/or their salts or derivatives are used in agents for repairing hair or increasing its gloss, volume or combability
AU2002309092A1 (en) * 2001-03-30 2002-10-15 L'oreal Compositions comprising at least one saccharide type compound and their use for the protection and/or repair of hair
WO2002096374A2 (en) 2001-05-31 2002-12-05 Upsher-Smith Laboratories, Inc. Dermatological compositions and methods comprising alpha-hydroxy acids or derivatives
JP5000049B2 (en) * 2001-08-27 2012-08-15 株式会社ファンケル Anti-aging agent
EP1297830A1 (en) * 2001-09-28 2003-04-02 Flamma Fabbrica Lombarda Ammino Acidi S.p.a. Use of alpha- or beta-amino acids, of the corresponding esters or of dipeptides of these amino acids with histidine derivatives in the prevention or treatment of tissue damage caused by a atmospheric ozone
US20050209131A1 (en) * 2001-11-16 2005-09-22 Singleton Laura C Composition containing peptides complexed with a copper ion
EP1455789A4 (en) * 2001-11-17 2008-02-13 Martinez Colon Maria Imiquimod therapies
US6824786B2 (en) * 2001-11-27 2004-11-30 Ruey J. Yu Compositions comprising phenyl-glycine derivatives
FR2834213B1 (en) * 2001-12-27 2004-06-04 Pharmascience Lab COSMETIC OR PHARMACEUTICAL COMPOSITION COMPRISING AT LEAST ONE ALKANOLAMIDE FOR INHIBITING LANGERHAN CELL MIGRATION, AND USES THEREOF
MC200053A1 (en) * 2002-01-04 2002-07-29 A M Exsymol S Use of L-arginine derivatives as photoprotective agents and optimizing the melanin response in cosmetic compositions
US6869598B2 (en) * 2002-03-22 2005-03-22 Unilever Home & Personal Care Usa Division Of Conopco, Inc. Stabilization of sunscreens in cosmetic compositions
AU2003220691A1 (en) * 2002-04-10 2003-10-27 Van Scott, Eugene J. Urea compositions
IL152397A (en) * 2002-10-21 2009-02-11 Hadasit Med Res Service Compositions and compounds for the treatment of hyperglycemia
US7374772B2 (en) * 2002-11-07 2008-05-20 Bommarito Alexander A Topical antifungal treatment
US20050019356A1 (en) * 2003-07-25 2005-01-27 The Procter & Gamble Company Regulation of mammalian keratinous tissue using N-acyl amino acid compositions
US20080076720A1 (en) * 2003-03-04 2008-03-27 Sancai Xie Personal care compositions having kinetin or zeatin
US20060063827A1 (en) * 2004-09-23 2006-03-23 Yu Ruey J Systemic administration of therapeutic amino acids and N-acetylamino acids
US20040214215A1 (en) * 2003-03-07 2004-10-28 Yu Ruey J. Bioavailability and improved delivery of alkaline pharmaceutical drugs
US20040220264A1 (en) * 2003-03-17 2004-11-04 Yu Ruey J Bioavailability and improved delivery of acidic pharmaceutical drugs
DE10316666B4 (en) * 2003-04-10 2015-04-09 Beiersdorf Ag Cosmetic or dermatological preparations with a combination of creatinine with creatine and coenzyme Q10
CN1886126A (en) * 2003-09-25 2006-12-27 Dmi生物科学公司 Methods and products which utilize N-acyl-L-aspartic acid
WO2005041870A2 (en) * 2003-10-24 2005-05-12 Ader Enterprises, Inc. Composition and method for the treatment of eye disease
CN100475184C (en) * 2003-10-31 2009-04-08 宝洁公司 Skin care composition containing dehydroacetic acid and skin care actives
MXPA06005546A (en) * 2003-11-21 2006-08-23 Nestec Sa Food composition comprising glucosamine.
JP5241058B2 (en) * 2003-11-27 2013-07-17 株式会社 資生堂 Keratinization inhibitor and pore-reducing agent
CN102274130B (en) 2003-11-27 2013-06-12 株式会社资生堂 Application of n- benzene sulfonyl-l-glutamic acid or saline thereof
WO2005055947A2 (en) * 2003-12-08 2005-06-23 Yu Ruey J Enlargement of mucocutaneous or cutaneous organs and sites with topical compositions
DE102004010717A1 (en) * 2004-03-03 2005-09-22 Beiersdorf Ag Cosmetic and/or dermatological preparation, useful as e.g. hair shampoo and to protect skin, hair and nails from sunlight (UV light), comprises polyquaternium-10, quaternized guar and creatine and/or its salts
US20050196418A1 (en) * 2004-03-04 2005-09-08 Yu Ruey J. Bioavailability and improved delivery of alkaline pharmaceutical drugs
JP4496375B2 (en) * 2004-05-21 2010-07-07 国立大学法人鳥取大学 Drugs for the treatment or treatment of wounds
US8338648B2 (en) * 2004-06-12 2012-12-25 Signum Biosciences, Inc. Topical compositions and methods for epithelial-related conditions
US7754875B1 (en) 2004-09-17 2010-07-13 Jfc Technologies, Llc Halide-free glucosamine base-organic acid salt compositions
WO2006054792A1 (en) * 2004-11-19 2006-05-26 Shiseido Company, Ltd. Springiness and stiffness improving agent for hair and cosmetic preparation for hair
US20060127342A1 (en) * 2004-12-09 2006-06-15 Georgia Levis Taurine-based compositions, therapeutic methods, and assays
US20060147504A1 (en) * 2004-12-30 2006-07-06 Bobby Corry Feminine anti-itch cloth
US20060166901A1 (en) * 2005-01-03 2006-07-27 Yu Ruey J Compositions comprising O-acetylsalicyl derivatives of aminocarbohydrates and amino acids
FR2880802B1 (en) * 2005-01-14 2008-12-19 Sederma Soc Par Actions Simpli COSMETIC OR DERMOPHARMACEUTICAL COMPOSITION CONTAINING EUGLENE EXTRACT
WO2006080924A1 (en) * 2005-01-27 2006-08-03 C.B. Fleet Company Incorporated Feminine anti-itch gel
US20060211754A1 (en) * 2005-03-16 2006-09-21 Yu Ruey J Compositions comprising N-propanoyl derivatives of amino acids, aminocarbohydrates and derivatives thereof
US20070020220A1 (en) * 2005-04-27 2007-01-25 Procter & Gamble Personal care compositions
US20080095732A1 (en) * 2005-04-27 2008-04-24 Rosemarie Osborne Personal care compositions
US9616011B2 (en) 2005-04-27 2017-04-11 The Procter & Gamble Company Personal care compositions
JP4865251B2 (en) * 2005-05-09 2012-02-01 株式会社 資生堂 Deficiency keratinization inhibitor, pore reducing agent, and composition for external use on skin
FR2885522B1 (en) * 2005-05-13 2020-01-10 Sederma COSMETIC OR DERMOPHARMACEUTICAL COMPOSITION CONTAINING TEPRENONE
US20060263309A1 (en) * 2005-05-17 2006-11-23 Bissett Donald L Regulation of mammalian keratinous tissue using personal care compositions comprising tetrahydrocurcumin
US20070020221A1 (en) * 2005-05-17 2007-01-25 Bissett Donald L Regulation of mammalian keratinous tissue using personal care compositions comprising cetyl pyridinium chloride
US20060263321A1 (en) * 2005-05-17 2006-11-23 The Procter & Gamble Company Regulation of mammalian keratinous tissue using personal care compositions comprising diethylhexyl syringylidene malonate
JP5014592B2 (en) * 2005-05-25 2012-08-29 株式会社 資生堂 Inadequate keratinization inhibitor, pore reducing agent, rough skin prevention / improving agent
WO2007001904A2 (en) * 2005-06-21 2007-01-04 The Procter & Gamble Company Personal care compositions comprising alpha-glucans and/or beta-glucans
US20100168468A1 (en) * 2005-07-26 2010-07-01 Kyowa Hakko Kirin Co., Ltd. Wrinkle-preventing and improving composition
FR2890310B1 (en) * 2005-09-06 2009-04-03 Sederma Soc Par Actions Simpli USE OF PROTOBERBERINS AS AGENTS REGULATING THE ACTIVITY OF THE PILOSEBACEE UNIT
JPWO2007034750A1 (en) * 2005-09-22 2009-03-26 株式会社資生堂 Wrinkle improver
EP1940346A2 (en) * 2005-09-30 2008-07-09 The Procter and Gamble Company Composition for regulation of mammalian keratinous tissue
CA2635603C (en) * 2005-11-30 2016-01-19 Endo Pharmaceuticals Inc. Treatment of xerostomia
US20070196292A1 (en) * 2005-11-30 2007-08-23 Robinson Larry R Personal care composition comprising dehydroacetate salts
US20070196296A1 (en) * 2005-12-13 2007-08-23 Rosemarie Osborne Personal care compositions
CN101330902A (en) * 2005-12-13 2008-12-24 宝洁公司 Personal care compositions comprising PPAR GAMMA antagonists
JP2007197371A (en) * 2006-01-26 2007-08-09 Yaizu Suisankagaku Industry Co Ltd Beautiful skin promoter and beauty and health food
WO2007093839A1 (en) * 2006-02-16 2007-08-23 Sederma New polypeptides kxk and their use
US20080031833A1 (en) * 2006-03-13 2008-02-07 Oblong John E Combined energy and topical composition application for regulating the condition of mammalian skin
WO2007107309A2 (en) * 2006-03-21 2007-09-27 Henkel Ag & Co. Kgaa Reductive colour removal
EP2001558A2 (en) * 2006-03-21 2008-12-17 Henkel AG & Co. KGaA Reductive colour removal
FR2900573B1 (en) 2006-05-05 2014-05-16 Sederma Sa NOVEL COSMETIC COMPOSITIONS COMPRISING AT LEAST ONE PEPTIDE CONTAINING AT LEAST ONE BLOCKED AROMATIC CYCLE
FR2901134B1 (en) * 2006-05-19 2008-10-03 Galderma Sa USE OF A COMPOSITION COMPRISING A COMBINATION OF HYDROQUINONE, FLUOCINOLONE ACETONIDE, AND TRETINOINE FOR THE TREATMENT OF CUTANEOUS SIGNALS OF PHOTOVEMENSIONING
ES2357571T3 (en) 2006-07-25 2011-04-27 Zambon S.P.A. COSMETIC OR DERMATOLOGICAL PREPARATIONS THAT INCLUDE N-ACETYLCISTEINE.
FR2904549B1 (en) * 2006-08-03 2012-12-14 Sederma Sa COMPOSITION COMPRISING SARSASAPOGENIN
WO2008101310A1 (en) * 2007-02-20 2008-08-28 Multi Formulations Ltd. Creatine-fatty acids
US7319157B1 (en) * 2007-02-20 2008-01-15 Multi Formulations Ltd. Creatine-fatty acids
WO2008101693A2 (en) 2007-02-22 2008-08-28 Beiersdorf Ag Cosmetic and pharmaceutical applications of n-acylated amino acids and structurally related compounds
US8469621B2 (en) * 2007-02-27 2013-06-25 The Procter & Gamble Company Personal care product having a solid personal care composition within a structure maintaining dispenser
WO2008104941A2 (en) * 2007-02-28 2008-09-04 The Procter & Gamble Company Personalcare composition comprising botanical extract of ficus benghalensis
US20090017080A1 (en) * 2007-03-15 2009-01-15 Paul Robert Tanner Personal care kit having skin care compositions with a readily perceptible difference
JP2009073806A (en) * 2007-08-27 2009-04-09 Iriya Cosmetics Co Ltd Insulin-like growth factor-1 secretagogue
US9119866B2 (en) 2008-04-08 2015-09-01 Huiru Wang Glycan-based drugs, therapies and biomarkers
US8426395B2 (en) 2008-05-30 2013-04-23 Northern Northern Innovations Holding Corp Preparations containing creatine and imino sugars
FR2935378B1 (en) * 2008-08-29 2015-03-27 Seppic Sa USE OF N-ACYL AMINOACIDS AS ACTIVE COSMETIC AND PHARMACEUTICAL PRINCIPLES, CAPABLE OF REDUCING THE INFLAMMATORY CONDITION OF SENESCENT REPLICATIVE FIBROBLASTS FROM HUMAN ADULT DERMAS; ANTI-AGE COSMETIC COMPOSITIONS
FR2939799B1 (en) 2008-12-11 2011-03-11 Sederma Sa COSMETIC COMPOSITION COMPRISING ACETYL OLIGOGLUCURONANS.
FR2941231B1 (en) 2009-01-16 2016-04-01 Sederma Sa NOVEL PEPTIDES, COMPOSITIONS COMPRISING THEM AND COSMETIC AND DERMO-PHARMACEUTICAL USES
WO2010082177A2 (en) 2009-01-16 2010-07-22 Sederma New compounds, in particular peptides, compositions comprising them and cosmetic and dermopharmaceutical uses
FR2941232B1 (en) 2009-01-16 2014-08-08 Sederma Sa NOVEL PEPTIDES, COMPOSITIONS COMPRISING THEM AND COSMETIC AND DERMO-PHARMACEUTICAL USES
US9676696B2 (en) 2009-01-29 2017-06-13 The Procter & Gamble Company Regulation of mammalian keratinous tissue using skin and/or hair care actives
FR2944435B1 (en) 2009-04-17 2011-05-27 Sederma Sa COSMETIC COMPOSITION COMPRISING ORIDONIN
FR2945939B1 (en) 2009-05-26 2011-07-15 Sederma Sa COSMETIC USE OF TYR-ARG DIPEPTIDE TO FIGHT SKIN RELEASE.
JP5564205B2 (en) * 2009-06-05 2014-07-30 焼津水産化学工業株式会社 Skin pruritus improving agent
US20100322983A1 (en) * 2009-06-22 2010-12-23 Susan Adair Griffiths-Brophy Personal-Care Composition
EP2459187B1 (en) 2009-07-29 2021-01-06 Olsen, Elise Compositions and methods for inhibiting hair growth
US20110039928A1 (en) * 2009-08-13 2011-02-17 Golini Jeffrey M Cetylated fatty acid and alkali buffered creatine anti-inflammatory composition
EP2552399A1 (en) 2010-04-01 2013-02-06 The Procter & Gamble Company Care polymers
US20110269657A1 (en) 2010-04-28 2011-11-03 Jiten Odhavji Dihora Delivery particles
US9993793B2 (en) 2010-04-28 2018-06-12 The Procter & Gamble Company Delivery particles
US9186642B2 (en) 2010-04-28 2015-11-17 The Procter & Gamble Company Delivery particle
US20120172281A1 (en) 2010-07-15 2012-07-05 Jeffrey John Scheibel Detergent compositions comprising microbially produced fatty alcohols and derivatives thereof
US9205284B2 (en) 2010-08-09 2015-12-08 Allele Biotechnology & Pharmaceuticals, Inc. Light-absorbing compositions and methods of use
US10842728B2 (en) 2010-08-09 2020-11-24 Allele Biotechnology & Pharmaceuticals, Inc. Light-absorbing compositions and methods of use
US9737472B2 (en) 2010-08-09 2017-08-22 Allele Biotechnology & Pharmaceuticals, Inc. Light-absorbing compositions and methods of use
DK2617707T3 (en) * 2010-08-27 2017-01-02 Neopharm Co Ltd Hitherto unknown compound that promotes secretion of human-derived antimicrobial peptide, process of preparation and composition with same as active ingredient
CN104257515B (en) * 2010-10-22 2017-05-03 新钰生技股份有限公司 Glycine derivate having function of inhibiting melanogenesis and whitening composition using same
IT1403257B1 (en) * 2010-12-06 2013-10-17 Intercos Italiana COSMETIC COMPOSITIONS CONTAINING COMPOUNDS WITH ANTI-GLYCATION ACTION, TO BE USED TO PREVENT AND SLOW DOWN THE CUTANEOUS AGING PROCESS
KR101298575B1 (en) * 2011-02-15 2013-08-22 대상 주식회사 The cosmetic composition containing n-acetyl-l-glutamine
WO2012138690A2 (en) 2011-04-07 2012-10-11 The Procter & Gamble Company Conditioner compositions with increased deposition of polyacrylate microcapsules
CN103458859A (en) 2011-04-07 2013-12-18 宝洁公司 Personal cleansing compositions with increased deposition of polyacrylate microcapsules
MX2013010983A (en) 2011-04-07 2013-10-30 Procter & Gamble Shampoo compositions with increased deposition of polyacrylate microcapsules.
US8802731B2 (en) * 2011-04-13 2014-08-12 Thermolife International, Llc N-acetyl beta alanine methods of use
CN103930167A (en) 2011-06-13 2014-07-16 宝洁公司 Personal care compositions comprising a di-amido gellant and methods of using
CN104039396A (en) 2011-06-13 2014-09-10 宝洁公司 PERSONAL CARE COMPOSITIONS COMPRISING A pH TUNEABLE GELLANT AND METHODS OF USING
EP2720666B1 (en) 2011-06-20 2019-03-20 The Procter and Gamble Company Personal care compositions comprising shaped abrasive particles
JP5702248B2 (en) * 2011-07-28 2015-04-15 三菱製紙株式会社 Nanofiber, method for forming nanofiber, and method for forming nanofiber aggregate
JP5254417B2 (en) * 2011-10-07 2013-08-07 株式会社 資生堂 Inadequate keratinization inhibitor, pore reducing agent, and rough skin prevention / improving agent
EP2771020B1 (en) 2011-10-28 2017-07-12 NeoStrata Company, Inc. N-acyldipeptide derivatives and their uses
EA031552B1 (en) * 2011-12-20 2019-01-31 Орифлейм Ресёрч Энд Девелопмент Лтд. Non-therapeutic cosmetic topical application of n-acetyl-l-aspartic acid
EP2814454A2 (en) 2012-02-14 2014-12-24 The Procter and Gamble Company Topical use of a skin-commensal prebiotic agent and compositions containing the same
WO2013142301A2 (en) 2012-03-19 2013-09-26 The Procter & Gamble Company Superabsorbent polymers and silicone elastomer for use in hair care compositions
US20130243834A1 (en) 2012-03-19 2013-09-19 The Procter & Gamble Company Cross linked silicone copolmyer networks in a thickened aqueous phase
US9549891B2 (en) 2012-03-19 2017-01-24 The Procter & Gamble Company Superabsorbent polymers and sunscreen actives for use in skin care compositions
US9271912B2 (en) 2012-06-13 2016-03-01 The Procter & Gamble Company Personal care compositions comprising a pH tuneable gellant and methods of using
US9259343B2 (en) 2012-07-06 2016-02-16 Newman Technologies LLC Device for mitigating plantar fasciitis
FR2996128B1 (en) * 2012-09-28 2015-01-02 Inneov Lab USE OF AN ASSOCIATION OF TAURINE OR ONE OF ITS DERIVATIVES, AND GRAPE EXTRACT FOR IMPROVING THE QUALITY OF NAILS.
GB201220354D0 (en) * 2012-11-12 2012-12-26 Medpharm Ltd Dermal compositions
US20140178314A1 (en) 2012-12-19 2014-06-26 The Procter & Gamble Company Compositions and/or articles with improved solubility of a solid active
US8865700B2 (en) 2012-12-20 2014-10-21 Avon Products, Inc. Collagen stimulators and their use in the treatment of skin
US9445981B2 (en) * 2012-12-20 2016-09-20 Avon Products, Inc PLOD-2 stimulators and their use in the treatment of skin
US8901122B2 (en) 2012-12-20 2014-12-02 Avon Products, Inc. Collagen stimulators and their use in the treatment of skin
US9511144B2 (en) 2013-03-14 2016-12-06 The Proctor & Gamble Company Cosmetic compositions and methods providing enhanced penetration of skin care actives
US20140314697A1 (en) * 2013-04-18 2014-10-23 Corum Inc. Method for Inhibiting Inflammation and Reducing Melanophilin Expression with Glycine Derivatives And the Composition Thereof
EP2994098A2 (en) 2013-05-10 2016-03-16 The Procter & Gamble Company Modular emulsion-based product differentiation
WO2014182996A2 (en) 2013-05-10 2014-11-13 The Procter & Gamble Company Modular emulsion-based product differentiation
CA2912226A1 (en) 2013-05-10 2014-11-13 The Procter & Gamble Company Modular emulsion-based product differentiation
US10328010B2 (en) * 2013-12-27 2019-06-25 Colgate-Palmolive Company Prebiotic oral care methods using a saccharide
US20150209468A1 (en) 2014-01-24 2015-07-30 The Procter & Gamble Company Hygiene article containing microorganism
EP3134064B1 (en) * 2014-04-24 2022-04-13 The Procter & Gamble Company Scalp care composition
US11813328B2 (en) * 2014-10-23 2023-11-14 Amgen Inc. Methods for reducing the viscosity of liquid pharmaceutical formulations comprising therapeutic proteins
EP3218507B1 (en) 2014-11-14 2020-01-08 The General Hospital Corporation Methods and compositions for enhancing skin pigmentation
ES2777775T3 (en) * 2014-12-04 2020-08-06 Professional Dietetics Int Srl In Forma Abbreviata Pd Int Srl Composition based on amino acids for the recovery of fibroelastin in dermal connective tissues
AU2016211605A1 (en) * 2015-01-27 2017-08-10 Florengale, Llc Healing topical composition
JP6692673B2 (en) * 2015-06-01 2020-05-13 株式会社コーセー Method for evaluating changes in intercellular lipids due to drugs, method for screening drugs, method for evaluating intercellular lipids
US20160354507A1 (en) 2015-06-07 2016-12-08 The Procter & Gamble Company Article of commerce containing absorbent article
JP6604637B2 (en) 2015-06-29 2019-11-13 ザ プロクター アンド ギャンブル カンパニー Superabsorbent polymers and starch powders for use in skin care compositions
US20170020750A1 (en) 2015-07-23 2017-01-26 The Procter & Gamble Company Patch containing microorganism
WO2017017585A1 (en) * 2015-07-26 2017-02-02 Mohan M Alapati Compound, composition and uses thereof
JP6346596B2 (en) * 2015-08-31 2018-06-20 株式会社ミルボン First agent for hair deformation and hair deformation treatment method
RU2018119510A (en) 2015-10-30 2019-12-05 Тимбер Фармасьютикалз ЭлЭлСи COMPOSITIONS OF ISOTRETINOIN AND THEIR APPLICATION AND METHODS
JP6159382B2 (en) * 2015-12-24 2017-07-05 花王株式会社 Oral UV resistance improver
EP3411243B1 (en) 2016-02-05 2021-12-01 The Procter & Gamble Company Methods of applying compositions to webs
EP3426212B1 (en) 2016-03-11 2020-10-21 The Procter and Gamble Company Compositioned, textured nonwoven webs
US20180071151A1 (en) 2016-09-09 2018-03-15 The Procter & Gamble Company Systems And Methods Of Applying Compositions To Webs And Webs Thereof
US10543240B2 (en) 2016-12-12 2020-01-28 Johnson & Johnson Consumer Inc. Topical composition containing glycerin and yeast extract
EA038207B1 (en) * 2017-02-13 2021-07-23 ЮНИЛЕВЕР АйПи ХОЛДИНГС Б.В. Method of strengthening hair
JP7210461B2 (en) * 2017-02-13 2023-01-23 ユニリーバー・アイピー・ホールディングス・ベスローテン・ヴェンノーツハップ Method for strengthening oxidized hair
KR102139678B1 (en) * 2017-11-24 2020-07-31 전북대학교 산학협력단 A Composition for Treating Atopy or Pruritus Comprising N-acetyl or N-acyl amino acid
WO2019103506A2 (en) * 2017-11-24 2019-05-31 전북대학교 산학협력단 Composition for treating atopy or pruritus comprising n-acetyl or n-acyl amino acid
MX2020011842A (en) 2018-05-10 2021-01-15 Unilever Ip Holdings B V Method of repairing oxidatively treated hair.
JP7048051B2 (en) * 2018-07-11 2022-04-05 正徳 染井 Atopic dermatitis remedy to reduce itching
CA3106898A1 (en) 2018-07-27 2020-01-30 Johnson & Johnson Surgical Vision, Inc. Compositions and methods for treating the eye
WO2020021481A1 (en) 2018-07-27 2020-01-30 Johnson & Johnson Vision Care, Inc. Compositions and methods for treating the eye
US11166997B2 (en) 2018-07-27 2021-11-09 Johnson & Johnson Surgical Vision, Inc. Compositions and methods for treating the eye
US11045416B2 (en) 2018-08-30 2021-06-29 Johnson & Johnson Consumer Inc. Topical compositions comprising Pichia anomala and retinol
US11110051B2 (en) 2018-08-30 2021-09-07 Johnson & Johnson Consumer Inc. Topical compositions comprising Pichia anomala and n-acetyl glucosamine
CN110870914A (en) * 2018-08-31 2020-03-10 成都夸常奥普医疗科技有限公司 Use of amino acid nutrients and pharmaceutical compositions containing same
CN110870860A (en) * 2018-08-31 2020-03-10 成都夸常奥普医疗科技有限公司 Pharmaceutical composition comprising amino acid nutrients and conventional ineffective compounds and use thereof
CN110870869A (en) * 2018-08-31 2020-03-10 成都夸常奥普医疗科技有限公司 Pharmaceutical composition comprising carbohydrate nutrients and conventional ineffective compounds and use thereof
CN112955115B (en) 2018-11-02 2023-06-30 联合利华知识产权控股有限公司 Bioenergy glyceryl nicotinate, compositions and methods of using the same
EP3914242A4 (en) * 2019-01-23 2023-02-01 Epitracker, Inc. Compositions and methods for diagnosis and treatment of conditions related to the quality of aging and longevity
EP3996669A1 (en) 2019-07-12 2022-05-18 Unilever Global Ip Limited Bioenergetic combinations and methods of using same
EP3996664A1 (en) 2019-07-12 2022-05-18 Unilever Global IP Limited Stabilization of resorcinol compounds in cosmetic compositions
US11865139B2 (en) 2020-11-12 2024-01-09 Thermolife International, Llc Method of treating migraines and headaches
US20220323388A1 (en) 2021-04-01 2022-10-13 Yu Ruey J Creatine, its derivatives, compositions and methods of use thereof
WO2023192538A1 (en) 2022-03-31 2023-10-05 Galderma Holding SA Personal care compositions for sensitive skin and methods of use

Citations (71)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3697652A (en) 1968-08-22 1972-10-10 Rotta Research Lab N-acetylglucosamine for treating degenerative afflictions of the joints
FR2244541A1 (en) 1973-08-01 1975-04-18 Fabre Sa Pierre Amino acid salts of quinine alkaloids - as phospho-lipase inhibitors and anti-acne agents
US3932622A (en) 1974-01-11 1976-01-13 General Foods Corporation Skin moisturizer
US4016287A (en) 1972-07-17 1977-04-05 Boehringer Ingelheim Gmbh Dermatological compositions containing an acylamino-carboxylic acid or an alkyl ester thereof
JPS52125637A (en) 1976-04-10 1977-10-21 Tanabe Seiyaku Co Ltd Permanent wave liquor
GB1503564A (en) 1974-02-25 1978-03-15 Thomas A Process for extracting and processing glycoproteins mucopolysaccharide and accompanying substances
US4165385A (en) * 1973-05-29 1979-08-21 Dianis Creations, Inc. Water-in-oil emulsion for skin moisturizing
JPS5679618A (en) 1979-11-30 1981-06-30 Tanabe Seiyaku Co Ltd Liquid for permanent wave
EP0057323A2 (en) * 1980-12-24 1982-08-11 Warner-Lambert Company Anticaries composition
CA1156028A (en) 1979-11-09 1983-11-01 Wolfgang K. F. Otto Mechanical surface finishing apparatus, process and product
JPS5913708A (en) 1982-07-14 1984-01-24 Shiseido Co Ltd Cosmetic
DE3435842A1 (en) 1984-09-29 1986-04-10 Wella Ag Use of N- alpha -acetyllysinamide in skin treatment compositions for increased bronzing of the skin
US4603146A (en) 1984-05-16 1986-07-29 Kligman Albert M Methods for retarding the effects of aging of the skin
JPS61210013A (en) 1985-03-13 1986-09-18 Iwase Kosufua Kk External preparation for skin
WO1987002244A1 (en) 1985-10-08 1987-04-23 Neil Geddes Clarkson Hendry Tissue growth regulation
US4661512A (en) 1984-10-31 1987-04-28 S. A. Panmedica Adamantanamine derivatives, processes for their preparation and drugs in which they are present
US4708965A (en) 1985-09-16 1987-11-24 Morgan Lee R Method of treating herpes virus infections with N,N'-diacetylcystine and derivatives
US4748022A (en) 1985-03-25 1988-05-31 Busciglio John A Topical composition
FR2609397A1 (en) 1988-02-23 1988-07-15 Serobiologiques Lab Sa Use of a substance or composition of carbohydrate nature as active principle of a dermatological and/or cosmetological and/or pharmaceutical and/or cell-stimulating composition, and composition containing such a substance or composition of carbohydrate nature
US4762822A (en) 1985-08-08 1988-08-09 Ettinger Anna C Reduction of gastrointestinal disease-producing organisms with sialic acid and gangliosides
EP0281812A1 (en) 1987-02-18 1988-09-14 Milor Scientific, Ltd. Composition for treatment of acne
US4772591A (en) 1985-09-25 1988-09-20 Peritain, Ltd. Method for accelerated wound healing
EP0308278A1 (en) 1987-09-02 1989-03-22 LES ETABLISSEMENTS GIVAUDAN LAVIROTTE & CIE Cosmetical use of N-acetylated or N-propionylated derivatives of proline, hydroxyproline and/or of the amino acids mixture resulting from the hydrolysis of collagen
US4827016A (en) 1985-09-16 1989-05-02 Morgan Lee R Method and compounds for reducing dermal inflammations
JPH01163110A (en) 1987-12-21 1989-06-27 Shiseido Co Ltd Preventive for aging of skin
EP0328099A1 (en) 1988-02-11 1989-08-16 Estee Lauder Inc. Tanning compositions and their use
US4870061A (en) 1986-01-29 1989-09-26 Ulrich Speck Use of N-acetylglucosamine for the therapy of degenerative joint disease and related diseases
EP0415598A1 (en) 1989-08-16 1991-03-06 Unilever Plc Cosmetic composition
US5017368A (en) * 1987-06-01 1991-05-21 Keikichi Sugiyama Composition for application to hair or scalp
EP0440298A1 (en) 1990-01-30 1991-08-07 Brocades Pharma B.V. Topical preparations for treating human nails
US5091171A (en) 1986-12-23 1992-02-25 Yu Ruey J Amphoteric compositions and polymeric forms of alpha hydroxyacids, and their therapeutic use
US5112613A (en) 1990-01-27 1992-05-12 Kyowa Hakko Kogyo Co., Ltd. Cosmetic composition
US5258391A (en) 1987-05-15 1993-11-02 Scott Eugene J Van Phenyl alpha acyloxyalkanoic acids, derivatives and their therapeutic use
US5286480A (en) 1992-06-29 1994-02-15 The Procter & Gamble Company Use of N-acetylated amino acid complexes in oral care compositions
US5300494A (en) 1986-06-06 1994-04-05 Union Carbide Chemicals & Plastics Technology Corporation Delivery systems for quaternary and related compounds
EP0627410A1 (en) 1992-12-09 1994-12-07 Kyowa Hakko Kogyo Co., Ltd. N-acylglutamine derivative
US5378455A (en) 1991-09-04 1995-01-03 Chesebrough-Ponds Usa Co., Division Of Conopco, Inc. Cosmetic composition for inhibiting hair growth
CA2164955A1 (en) 1993-06-18 1995-01-05 Richard J. Sharpe Method for treating hyperkeratosis and diseases mediated by proteases
US5380359A (en) 1992-03-31 1995-01-10 Kyowa Hakko Kogyo Co., Ltd. Cosmetics based on naturally derived melanin-coated pigments
US5385938A (en) 1986-12-23 1995-01-31 Yu; Ruey J. Method of using glycolic acid for treating wrinkles
US5422370A (en) 1986-12-23 1995-06-06 Tristrata Inc Method of using 2-hydroxypropanoic acid (lactic acid) for the treatment of wrinkles
US5428026A (en) * 1991-05-24 1995-06-27 Nestec S.A. Liposoluble antioxidant mixture
US5451405A (en) 1994-04-25 1995-09-19 Chesebrough-Pond's Usa Co. Skin treatment composition
US5468476A (en) 1994-03-16 1995-11-21 Ahluwalia; Gurpreet S. Reduction of hair growth
US5472698A (en) 1994-12-20 1995-12-05 Elizabeth Arden Co., Division Of Conopco, Inc. Composition for enhancing lipid production in skin
JPH08143588A (en) 1994-11-24 1996-06-04 Kose Corp Glucosamine derivative and cosmetic containing the same
US5525336A (en) 1993-02-19 1996-06-11 Green; Howard Cosmetic containing comeocyte proteins and transglutaminase, and method of application
US5547988A (en) 1986-12-23 1996-08-20 Tristrata Technology, Inc. Alleviating signs of dermatological aging with glycolic acid, lactic acid or citric acid
US5547658A (en) 1992-03-03 1996-08-20 L'oreal Cosmetic composition containing melaninlike pigments in combination with certain tocopherols, and process for protecting the skin, hair, mucosae and cosmetic compositions
US5607921A (en) 1994-01-31 1997-03-04 L'oreal Stabilized cosmetic or dermatological composition containing several precursors of the same active agent in order to maximize its release, and use thereof
US5612324A (en) * 1992-05-05 1997-03-18 The Procter & Gamble Company Method for treating acne
WO1997012597A1 (en) 1995-10-04 1997-04-10 L'oreal Use of carbohydrates for promoting skin exfoliation
EP0768079A1 (en) 1994-06-30 1997-04-16 Kyowa Hakko Kogyo Co., Ltd. Hair growth stimulant
WO1997015283A1 (en) 1995-10-25 1997-05-01 The Procter & Gamble Company Topical compositions containing n-acetylcysteine and odor masking materials
US5641475A (en) 1987-05-15 1997-06-24 Tristrata, Inc. Antiodor, antimicrobial and preservative compositions and methods of using same
US5643949A (en) 1987-05-15 1997-07-01 Tristrata, Inc. Phenyl alpha acyloxyalkanoic acids, derivatives and their therapeutic use
US5650166A (en) 1993-12-30 1997-07-22 L'oreal Moisturizing composition for the simultaneous treatment of the surface layers and deep layers of the skin, and use thereof
US5652273A (en) 1995-11-30 1997-07-29 Henry; James Reduction of hair growth
CN1156028A (en) 1996-12-27 1997-08-06 中国人民解放军第三军医大学 Application of N-aceto-D-aminoglucose for preparing skin sanitary article preparation
US5665776A (en) 1986-12-23 1997-09-09 Tristrata Technology, Inc. Additives enhancing topical actions of therapeutic agents
US5677285A (en) 1992-08-03 1997-10-14 Fidia S.P.A. Derivatives of neuraminic acid
JPH09323915A (en) 1996-06-05 1997-12-16 Ichimaru Pharcos Co Ltd Melanin generation inhibitor consisting of n-acetylthyrosine derivative as active ingredient and application of the same to skin preparation for external use and bath agent
US5728373A (en) 1992-08-26 1998-03-17 Beiersdorf Ag Cosmetic and dermatological sunscreen compositions containing thiols and/or thiol derivates
EP0852946A2 (en) 1996-11-29 1998-07-15 Gianfranco De Paoli Ambrosi Composition for cosmetic, pharmaceutical or dietetic use based on an amino-sugar and/or a polyhydroxylic acid
US5804594A (en) * 1997-01-22 1998-09-08 Murad; Howard Pharmaceutical compositions and methods for improving wrinkles and other skin conditions
WO1998052576A1 (en) 1997-05-21 1998-11-26 New Key Foods N.V. Use of glucosamine and glucosamine derivatives for quick alleviation of itching or localized pain
US5853705A (en) 1996-03-27 1998-12-29 Shiseido Company, Ltd. Anti-aging cosmetic composition
US5866142A (en) * 1995-07-20 1999-02-02 Riordan; Neil H. Skin treatment system
US5939082A (en) * 1995-11-06 1999-08-17 The Procter & Gamble Company Methods of regulating skin appearance with vitamin B3 compound
US6149924A (en) 1998-07-20 2000-11-21 Biomed Research & Technologies, Inc. Composition for enhancing lipid production, barrier function, hydrogen peroxide neutralization, and moisturization of the skin
US6159485A (en) 1999-01-08 2000-12-12 Yugenic Limited Partnership N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3856934A (en) * 1970-06-24 1974-12-24 A Kligman Skin depigmentation
DE2330927C2 (en) * 1973-06-18 1983-11-10 Ideal-Standard Gmbh, 5300 Bonn Sanitary water valve made of plastic
US4176197A (en) * 1978-02-03 1979-11-27 Dominion Pharmacal, Inc. Method for treating acne vulgaris
JPS56155298A (en) * 1980-05-02 1981-12-01 Tanabe Seiyaku Co Shampoo composition
IT1183530B (en) * 1985-03-29 1987-10-22 Monteluos S P A COMPOSITIONS FOR COSMETICS INCLUDING PERFLUOROPOLYETERS
GB2180153A (en) * 1985-09-10 1987-03-25 Rory Ltd Compositions containing acetylcysteine
US5470567A (en) * 1989-08-24 1995-11-28 Bristol Myers Squibb Company Synergistic skin depigmentation composition
JPH0578243A (en) * 1990-12-11 1993-03-30 Shiseido Co Ltd Antipruritic agent and antipruritic composition
US5296500A (en) * 1991-08-30 1994-03-22 The Procter & Gamble Company Use of N-acetyl-cysteine and derivatives for regulating skin wrinkles and/or skin atrophy
JP3485375B2 (en) * 1995-02-17 2004-01-13 株式会社資生堂 External preparation for skin
US5776920A (en) * 1995-08-02 1998-07-07 Quarles; Ruth Method for treatment of psoriasis
GB9606429D0 (en) * 1996-03-27 1996-06-05 Boots Co Plc Pharmaceutical compositions
US5728371A (en) * 1996-04-29 1998-03-17 L'oreal, S.A. Skin protection, fragrance enhancing and vitamin delivery composition
US5993787A (en) * 1996-09-13 1999-11-30 Johnson & Johnson Consumer Products, Inc. Composition base for topical therapeutic and cosmetic preparations
CN1161198A (en) * 1996-10-29 1997-10-08 贾增申 External ointment for eliminating wrinkle and scar on skin
JPH10163110A (en) * 1996-11-27 1998-06-19 Kyocera Corp Semiconductor device
US9616534B2 (en) 2013-11-25 2017-04-11 Invent-A-Part Modular structures for motion stages

Patent Citations (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3697652A (en) 1968-08-22 1972-10-10 Rotta Research Lab N-acetylglucosamine for treating degenerative afflictions of the joints
US4016287A (en) 1972-07-17 1977-04-05 Boehringer Ingelheim Gmbh Dermatological compositions containing an acylamino-carboxylic acid or an alkyl ester thereof
US4165385A (en) * 1973-05-29 1979-08-21 Dianis Creations, Inc. Water-in-oil emulsion for skin moisturizing
FR2244541A1 (en) 1973-08-01 1975-04-18 Fabre Sa Pierre Amino acid salts of quinine alkaloids - as phospho-lipase inhibitors and anti-acne agents
US3932622A (en) 1974-01-11 1976-01-13 General Foods Corporation Skin moisturizer
GB1503564A (en) 1974-02-25 1978-03-15 Thomas A Process for extracting and processing glycoproteins mucopolysaccharide and accompanying substances
JPS52125637A (en) 1976-04-10 1977-10-21 Tanabe Seiyaku Co Ltd Permanent wave liquor
CA1156028A (en) 1979-11-09 1983-11-01 Wolfgang K. F. Otto Mechanical surface finishing apparatus, process and product
JPS5679618A (en) 1979-11-30 1981-06-30 Tanabe Seiyaku Co Ltd Liquid for permanent wave
EP0057323A2 (en) * 1980-12-24 1982-08-11 Warner-Lambert Company Anticaries composition
JPS5913708A (en) 1982-07-14 1984-01-24 Shiseido Co Ltd Cosmetic
US4603146A (en) 1984-05-16 1986-07-29 Kligman Albert M Methods for retarding the effects of aging of the skin
DE3435842A1 (en) 1984-09-29 1986-04-10 Wella Ag Use of N- alpha -acetyllysinamide in skin treatment compositions for increased bronzing of the skin
US4661512A (en) 1984-10-31 1987-04-28 S. A. Panmedica Adamantanamine derivatives, processes for their preparation and drugs in which they are present
JPS61210013A (en) 1985-03-13 1986-09-18 Iwase Kosufua Kk External preparation for skin
US4748022A (en) 1985-03-25 1988-05-31 Busciglio John A Topical composition
US4762822A (en) 1985-08-08 1988-08-09 Ettinger Anna C Reduction of gastrointestinal disease-producing organisms with sialic acid and gangliosides
US4708965A (en) 1985-09-16 1987-11-24 Morgan Lee R Method of treating herpes virus infections with N,N'-diacetylcystine and derivatives
US4827016A (en) 1985-09-16 1989-05-02 Morgan Lee R Method and compounds for reducing dermal inflammations
US4772591A (en) 1985-09-25 1988-09-20 Peritain, Ltd. Method for accelerated wound healing
WO1987002244A1 (en) 1985-10-08 1987-04-23 Neil Geddes Clarkson Hendry Tissue growth regulation
US4870061A (en) 1986-01-29 1989-09-26 Ulrich Speck Use of N-acetylglucosamine for the therapy of degenerative joint disease and related diseases
US5300494A (en) 1986-06-06 1994-04-05 Union Carbide Chemicals & Plastics Technology Corporation Delivery systems for quaternary and related compounds
US5422370A (en) 1986-12-23 1995-06-06 Tristrata Inc Method of using 2-hydroxypropanoic acid (lactic acid) for the treatment of wrinkles
US5091171B2 (en) 1986-12-23 1997-07-15 Tristrata Inc Amphoteric compositions and polymeric forms of alpha hydroxyacids and their therapeutic use
US5091171B1 (en) 1986-12-23 1995-09-26 Ruey J Yu Amphoteric compositions and polymeric forms of alpha hydroxyacids, and their therapeutic use
US5547988B1 (en) 1986-12-23 1997-07-15 Tristrata Inc Alleviating signs of dermatological aging with glycolic acid lactic acid or citric acid
US5470880A (en) 1986-12-23 1995-11-28 Tristrata Inc Method of using citric acid for the treatment of wrinkles
US5385938A (en) 1986-12-23 1995-01-31 Yu; Ruey J. Method of using glycolic acid for treating wrinkles
US5422370B1 (en) 1986-12-23 1997-07-15 Tristrata Inc Method of using 2-hydroxypropanoic acid (lactic acid) for the treatment of wrinkles
US5091171A (en) 1986-12-23 1992-02-25 Yu Ruey J Amphoteric compositions and polymeric forms of alpha hydroxyacids, and their therapeutic use
US5547988A (en) 1986-12-23 1996-08-20 Tristrata Technology, Inc. Alleviating signs of dermatological aging with glycolic acid, lactic acid or citric acid
US5665776A (en) 1986-12-23 1997-09-09 Tristrata Technology, Inc. Additives enhancing topical actions of therapeutic agents
US5385938B1 (en) 1986-12-23 1997-07-15 Tristrata Inc Method of using glycolic acid for treating wrinkles
EP0281812A1 (en) 1987-02-18 1988-09-14 Milor Scientific, Ltd. Composition for treatment of acne
US5643949A (en) 1987-05-15 1997-07-01 Tristrata, Inc. Phenyl alpha acyloxyalkanoic acids, derivatives and their therapeutic use
US5258391A (en) 1987-05-15 1993-11-02 Scott Eugene J Van Phenyl alpha acyloxyalkanoic acids, derivatives and their therapeutic use
US5641475A (en) 1987-05-15 1997-06-24 Tristrata, Inc. Antiodor, antimicrobial and preservative compositions and methods of using same
US5017368A (en) * 1987-06-01 1991-05-21 Keikichi Sugiyama Composition for application to hair or scalp
EP0308278A1 (en) 1987-09-02 1989-03-22 LES ETABLISSEMENTS GIVAUDAN LAVIROTTE & CIE Cosmetical use of N-acetylated or N-propionylated derivatives of proline, hydroxyproline and/or of the amino acids mixture resulting from the hydrolysis of collagen
JPH01163110A (en) 1987-12-21 1989-06-27 Shiseido Co Ltd Preventive for aging of skin
EP0328099A1 (en) 1988-02-11 1989-08-16 Estee Lauder Inc. Tanning compositions and their use
FR2609397A1 (en) 1988-02-23 1988-07-15 Serobiologiques Lab Sa Use of a substance or composition of carbohydrate nature as active principle of a dermatological and/or cosmetological and/or pharmaceutical and/or cell-stimulating composition, and composition containing such a substance or composition of carbohydrate nature
EP0415598A1 (en) 1989-08-16 1991-03-06 Unilever Plc Cosmetic composition
US5112613A (en) 1990-01-27 1992-05-12 Kyowa Hakko Kogyo Co., Ltd. Cosmetic composition
EP0440298A1 (en) 1990-01-30 1991-08-07 Brocades Pharma B.V. Topical preparations for treating human nails
US5428026A (en) * 1991-05-24 1995-06-27 Nestec S.A. Liposoluble antioxidant mixture
US5378455A (en) 1991-09-04 1995-01-03 Chesebrough-Ponds Usa Co., Division Of Conopco, Inc. Cosmetic composition for inhibiting hair growth
US5547658A (en) 1992-03-03 1996-08-20 L'oreal Cosmetic composition containing melaninlike pigments in combination with certain tocopherols, and process for protecting the skin, hair, mucosae and cosmetic compositions
US5380359A (en) 1992-03-31 1995-01-10 Kyowa Hakko Kogyo Co., Ltd. Cosmetics based on naturally derived melanin-coated pigments
US5612324A (en) * 1992-05-05 1997-03-18 The Procter & Gamble Company Method for treating acne
US5286480A (en) 1992-06-29 1994-02-15 The Procter & Gamble Company Use of N-acetylated amino acid complexes in oral care compositions
US5677285A (en) 1992-08-03 1997-10-14 Fidia S.P.A. Derivatives of neuraminic acid
US5728373A (en) 1992-08-26 1998-03-17 Beiersdorf Ag Cosmetic and dermatological sunscreen compositions containing thiols and/or thiol derivates
EP0627410A1 (en) 1992-12-09 1994-12-07 Kyowa Hakko Kogyo Co., Ltd. N-acylglutamine derivative
US5525336A (en) 1993-02-19 1996-06-11 Green; Howard Cosmetic containing comeocyte proteins and transglutaminase, and method of application
CA2164955A1 (en) 1993-06-18 1995-01-05 Richard J. Sharpe Method for treating hyperkeratosis and diseases mediated by proteases
US5650166A (en) 1993-12-30 1997-07-22 L'oreal Moisturizing composition for the simultaneous treatment of the surface layers and deep layers of the skin, and use thereof
US5607921A (en) 1994-01-31 1997-03-04 L'oreal Stabilized cosmetic or dermatological composition containing several precursors of the same active agent in order to maximize its release, and use thereof
US5468476A (en) 1994-03-16 1995-11-21 Ahluwalia; Gurpreet S. Reduction of hair growth
US5451405A (en) 1994-04-25 1995-09-19 Chesebrough-Pond's Usa Co. Skin treatment composition
EP0768079A1 (en) 1994-06-30 1997-04-16 Kyowa Hakko Kogyo Co., Ltd. Hair growth stimulant
JPH08143588A (en) 1994-11-24 1996-06-04 Kose Corp Glucosamine derivative and cosmetic containing the same
US5472698A (en) 1994-12-20 1995-12-05 Elizabeth Arden Co., Division Of Conopco, Inc. Composition for enhancing lipid production in skin
US5866142A (en) * 1995-07-20 1999-02-02 Riordan; Neil H. Skin treatment system
WO1997012597A1 (en) 1995-10-04 1997-04-10 L'oreal Use of carbohydrates for promoting skin exfoliation
WO1997015283A1 (en) 1995-10-25 1997-05-01 The Procter & Gamble Company Topical compositions containing n-acetylcysteine and odor masking materials
US5733535A (en) 1995-10-25 1998-03-31 The Procter & Gamble Co. Topical compositions containing N-acetylcysteine and odor masking materials
US5939082A (en) * 1995-11-06 1999-08-17 The Procter & Gamble Company Methods of regulating skin appearance with vitamin B3 compound
US5652273A (en) 1995-11-30 1997-07-29 Henry; James Reduction of hair growth
US5853705A (en) 1996-03-27 1998-12-29 Shiseido Company, Ltd. Anti-aging cosmetic composition
JPH09323915A (en) 1996-06-05 1997-12-16 Ichimaru Pharcos Co Ltd Melanin generation inhibitor consisting of n-acetylthyrosine derivative as active ingredient and application of the same to skin preparation for external use and bath agent
EP0852946A2 (en) 1996-11-29 1998-07-15 Gianfranco De Paoli Ambrosi Composition for cosmetic, pharmaceutical or dietetic use based on an amino-sugar and/or a polyhydroxylic acid
US6147054A (en) * 1996-11-29 2000-11-14 De Paoli Ambrosi; Gianfranco Composition for cosmetic, pharmaceutical or dietetic use based on an amino sugar and/or a polyhydroxylic acid
CN1156028A (en) 1996-12-27 1997-08-06 中国人民解放军第三军医大学 Application of N-aceto-D-aminoglucose for preparing skin sanitary article preparation
US5804594A (en) * 1997-01-22 1998-09-08 Murad; Howard Pharmaceutical compositions and methods for improving wrinkles and other skin conditions
WO1998052576A1 (en) 1997-05-21 1998-11-26 New Key Foods N.V. Use of glucosamine and glucosamine derivatives for quick alleviation of itching or localized pain
US6149924A (en) 1998-07-20 2000-11-21 Biomed Research & Technologies, Inc. Composition for enhancing lipid production, barrier function, hydrogen peroxide neutralization, and moisturization of the skin
US6159485A (en) 1999-01-08 2000-12-12 Yugenic Limited Partnership N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use
US6524593B1 (en) 1999-01-08 2003-02-25 Ruey J. Yu N-acetyl aldosamines and related N-acetyl compounds, and their topical use
USRE41339E1 (en) * 1999-01-08 2010-05-18 Tristrata, Inc. N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use

Non-Patent Citations (21)

* Cited by examiner, † Cited by third party
Title
Acetylcylsteme as a Bleaching Agent in the Treatment of Melasma, Netherlands Institute for Pigment Disorders, 1993-2003.
Breborowicz, A. et al; Article Abstracts of the XVIIIth Annual Conference on Peritoneal Dialysis. Nashville, TN, "N-Acetylglucosamine (NAG) Enhances Glycosaminoglycans (GAGs) Synthesis by Human Peritoneal Mesothelial Cells (MC) and Fibrobtasts (FB)"; Feb. 23-25, 1998: 2 pages.
Database WPI, Section Ch. Week 198133 Derwent Publications Ltd., London GB, AN 1981-59656D, XP002138487, Jun. 30, 1981, (Abstract).
Database WPI, Section Ch. Week 198133 Derwent Publications Ltd., London GB, AN 1982-00887E, XP 002138486, Dec. 1, 1981. (Abstract).
Database WPI, Section Ch. Week 198644 Derwent Publications Ltd., London GB, AN 1986-287932, XP002138488, Sep. 18, 1986. (Abstract).
Database WPI, Section Ch. Week 199809 Derwent Publications Ltd., London GB, AN 1998-095650, XP002138489, Dec. 16, 1997. (Abstract).
English Translation of Japanese Patent 09323915-A Dec. 16, 1997.
European Search Report in related application 10 00 6974 mailed Mar. 7, 2011.
Gudasheva et al. Nootropic action of proline-based topological analogs of piractern, Pharmaceutical Chemistry Journal 1991, 25(6), 363-367.
Hackemuller, Doris, B.C . Lippold, XP009053417 Jun. 30, 1990.
Hollingshead et al., "Topical Compositions Containing N-ActeylCysteine and Odor Masking Materials", May 1, 1997, International Application Published Under the PCT, WO 97/15283.
Kligman, et al., "Topical tretinoin for photoaged skin," Supplement to the Journal of the American Academy of Dermatology, vol. 15, No. 4, Part 2, pp. 836-859 (Oct. 1986).
Milikovic, Momcilo et al, "Stereoselective Aldol Condensations with Sugar Aldehydes. Condensation of 2-Acetamido-2-Deoxy-D-and-I-Glyceraldehyde with DI-tert-Butyl Oxaloacetate", Momcilo Milijkovic and Peter Hagel, Jun. 25, 1984, Elsevier Science Publishers B.V., Amsterdam XP001206285, Carbohydrate Research: 141 (1985) 213-220.
Mishima, Yutaka et al., Selective Aberration and Pigment Loss in Melanosomes of Malignant Melanoma Cells in Vitro by Glycosylation Inhibitors: Premelanosomes as Glycoprotein, vol. 81, No. 2, The Journal of Investigative Dermatology, by Yutaka Mishima, M,D., Ph.D, and Genji Imokawa, M.S. 1983.
Sharps et al. Method for Treating Hyperkeratosis and Diseases Mediated by Proteases, International Application Published Under the PCT WO 95/00136 1995.
Susumu, Honda et al, "Analysis of the Component Aldehyde and Alcohols in Borohydride-Reduced Dialdehydes from Hexosamine Derivatives", Susumu Honda, Kazuaki Kakehi and Kazunorii Mukai, Faculty of Pharmaceutical Sciences, Kinki University, Kowakae, Higashio-saka (Japan), May 30, 1979, Analytica Chimica Acta, 111, (1979) 227-234, Elsevier Scientific Publishing Company, Amsterdam XP001206286.
The Merck Manual of Medical Information-Second Home Edition: Skin Disorder (Sunlight and Skin Damage), 2003.
The Merck Manual, Sixteenth Editional, Dermatological Disorders: Disorders of Hair Follicles and Sebaceous Glands, Pseudofolliculitis Barbae, 1992, p. 2434.
The Merk Manual, Sixteenth Edition, Dermatological Discorders: Actinic Kerotoses, 1992, p. 2432 (previously submitted).
Uber Sphingesin von E. Klenk und H. Faillard, Ans dem Physiologisch-Chemischen Institut der Universitat Kola (Der Schriffleitung zugegangen am Sep. 15, 1954).
Yano H. et al., "Effects of N-Acetyl-D-Glucosamine on Wound Healing in Rats", MIE Medical Journal, TSU, JP, vol. XXXV, No. 1, 1985, pp. 53-56, XP002997084, ISSN: 0026-3532.

Also Published As

Publication number Publication date
EP2080504A2 (en) 2009-07-22
DE60022162T3 (en) 2011-09-29
DE60022162T2 (en) 2006-03-23
EP2311452B2 (en) 2020-12-30
EP2311452B9 (en) 2014-12-24
WO2000040217A1 (en) 2000-07-13
USRE42902E1 (en) 2011-11-08
EP1639994A2 (en) 2006-03-29
USRE41339E1 (en) 2010-05-18
EP2311452B1 (en) 2014-04-02
AU2408000A (en) 2000-07-24
WO2000040217B1 (en) 2000-10-05
MXPA01006917A (en) 2003-06-04
DE60022162D1 (en) 2005-09-29
ES2477556T3 (en) 2014-07-17
US6159485A (en) 2000-12-12
EP1143925B2 (en) 2011-01-26
DE60041934D1 (en) 2009-05-14
EP1570840A2 (en) 2005-09-07
USRE44017E1 (en) 2013-02-19
BR0007430A (en) 2001-10-16
EP1570840B1 (en) 2009-04-01
US6524593B1 (en) 2003-02-25
EP1143925A1 (en) 2001-10-17
AU775209B2 (en) 2004-07-22
HK1156853A1 (en) 2012-06-22
CA2778317C (en) 2014-09-16
ES2248042T5 (en) 2011-06-03
USRE41278E1 (en) 2010-04-27
ES2325160T3 (en) 2009-08-27
CA2683980A1 (en) 2000-07-13
CA2683980C (en) 2012-08-07
EP1143925B1 (en) 2005-08-24
EP1570840A3 (en) 2005-11-16
ES2248042T3 (en) 2006-03-16
CN1336817A (en) 2002-02-20
EP2311452A1 (en) 2011-04-20
CA2358457A1 (en) 2000-07-13
CA2778317A1 (en) 2000-07-13
JP2012072172A (en) 2012-04-12
CA2358457C (en) 2010-03-23
JP2002534369A (en) 2002-10-15

Similar Documents

Publication Publication Date Title
USRE44302E1 (en) N-acetyl aldosamines, N-acetylamino acids and related N-acetyl compounds and their topical use
US20030229141A1 (en) N-acetyl cysteine and its topical use
US6335023B1 (en) Oligosaccharide aldonic acids and their topical use
US20110091403A1 (en) Oligosaccharide aldonic acids and their topical use
US6808716B2 (en) N-acetylamino acids, related N-acetyl compounds and their topical use
US20040147452A1 (en) Non-amphoteric glutathione derivative compositions for tropical application
AU2004212601B2 (en) Oligosaccharide aldonic acids and their topical use
EP1685843A1 (en) Oligosaccharide aldonic acids and their topical use