US20160030584A1 - Method for preserving and stabilising proteins, which can be used for industrial development of formulations of sanitary, pharmaceutical and cosmetic products - Google Patents

Method for preserving and stabilising proteins, which can be used for industrial development of formulations of sanitary, pharmaceutical and cosmetic products Download PDF

Info

Publication number
US20160030584A1
US20160030584A1 US14/759,320 US201414759320A US2016030584A1 US 20160030584 A1 US20160030584 A1 US 20160030584A1 US 201414759320 A US201414759320 A US 201414759320A US 2016030584 A1 US2016030584 A1 US 2016030584A1
Authority
US
United States
Prior art keywords
proteins
pharmaceutical
preserving
formulations
sanitary
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.)
Abandoned
Application number
US14/759,320
Inventor
Teodoro MAYAYO FALO
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.)
SANI-RED SL
Original Assignee
SANI-RED SL
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
Application filed by SANI-RED SL filed Critical SANI-RED SL
Assigned to SANI-RED, S.L. reassignment SANI-RED, S.L. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MAYAYO FALO, TEODORO
Publication of US20160030584A1 publication Critical patent/US20160030584A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1808—Epidermal growth factor [EGF] urogastrone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1825—Fibroblast growth factor [FGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1841—Transforming growth factor [TGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions

Definitions

  • the invention as stated the title of the present specification, relates to a method for preserving and stabilising proteins, which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products.
  • the object of the invention is focused on a method which envisages the creation of a dispersed system as a means for preservation, stabilization and storage of proteins in an oily phase under normal pressure and temperature conditions.
  • the method proposed by the invention is based on the incorporation of proteins, such as cell growth factors such as tales epidermal growth factor (EGF) and fibroblast growth factor (bFGF), although not limited thereto, in a medium composed of components, such as grape seed oil, a base consisting of various compounds that will be specified later in the present description, and butylhydroxytoluene (BHT), that form the cited oily phase.
  • proteins such as cell growth factors such as tales epidermal growth factor (EGF) and fibroblast growth factor (bFGF), although not limited thereto, in a medium composed of components, such as grape seed oil, a base consisting of various compounds that will be specified later in the present description, and butylhydroxytoluene (BHT), that form the cited oily phase.
  • EGF epi
  • the method proposed takes advantage of some chemical groups of the oily phase components promote certain physical-chemical interactions with the residues of proteins that enhance for longer periods of time the maintenance of the native molecular structure of proteins, achieving that such method is simple, economical and of general application, with potential capacity to replace complex preservation techniques and/or aqueous means commonly used for the preservation of proteins.
  • the field of application of the present invention falls within the industrial chemical sector, focusing particularly on the scope of the industry dedicated to the manufacture of pharmaceutical and cosmetic products, in particular those intended to preserve growth factors.
  • Proteins are used as active substances of numerous treatments in diseases such as diabetes, cancer, haemophilia, myocardial infarction, just to cite some pathologies [Krishnamurthy and Manning, 2002].
  • protein structures such as growth factors, e.g. the EGF, aroused a great interest in the cosmetic industry in recent years. So, if a protein can not be properly stabilized, it may lose its native structure with consequent loss of its biological activity [Krishnamurthy and Manning, 2002].
  • the problem is that the protein stabilization is particularly difficult since they are very susceptible to degradation phenomena: physical, chemical and enzymatic.
  • Chemical degradation is related to deamination, oxidation, reduction, hydrolysis processes and chemical interactions such as disulfide bond interactions.
  • Physical degradation includes surface adsorption, aggregation, dissociation, denaturation, and photolysis processes.
  • the EGF was the first polypeptide isolated and characterized as a growth factor. It has a biological activity related to its native structure capable of stimulating the proliferation of keratinocytes and fibroblasts (with the consequent formation of collagen), induces angiogenesis (formation of new vessels) and performs subsequent vascularisation of the area where it is applied. These properties promote the appearance of new skin with a considerable thick, restoring its elasticity and firmness, thus diminishing the unwanted effects of cellular oxidation and therefore resulting in the elimination of wrinkles [Tang et al., 1994].
  • Such growth factor has begun to use recently in topical formulations, where very good results have been obtained related to tissue regeneration, the acceleration in the healing of burns, treatment of keloid, acne and stretch marks, even improving outcomes of treatments of surgical type, promotion of the consolidation of skin grafts as well as the post-peeling application.
  • said proteins are increasingly used in the pharmaceutical and cosmetic industry, but have not been used massively due to its high prices and their difficult stabilisation [Schouest et al., 2012].
  • Fibroblast growth factor is a growth factor that acts to increase the mitotic activity index and DNA synthesis, facilitating the proliferation of various precursor cells, such as chondroblasts, collagenoblasts, and osteoblasts, etc., that form the body's fibrous, connective, and support tissues. It contributes to wound healing, haematopoiesis, angiogenesis, or the embryonic development.
  • the object of the present invention is, therefore, the development of a new method for preserving and stabilising proteins, which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products that, unlike conventional methods, it takes place in oily phase so that it is more simple and economical, having noted that, at least by the applicant, the existence of any document or invention that discloses a method for preserving and stabilising proteins or similar invention that has technical characteristics similar to those here proposed is unaware.
  • EGF EGF
  • bFGF EGF
  • other cell growth factors and/or proteins are macromolecules with difficult stabilization, since, currently, the majority of dispersion means have aqueous character and achieve the stabilization in a short period of time, through the use of dispersed systems such as emulsions, or expensive and very specific methods that do not ensure a longer life of the protein native structure, such as lyophilisation.
  • the development of the EGF and other growth factors and/or proteins has been carried out in oily medium as an intermediate product for use in specific industrial processes, promoting the stability of proteins with respect to the currently existing methods thus achieving a more effective action to the not denatured proteins in such medium not being denatured the proteins in such medium.
  • the growth factors are surrounded by an anhydrous medium composed of other components that act as adjuvants interacting with the residues of proteins, such components being: grape seed oil, that creates a medium which reduces the electrostatic interactions with the protein residues while maintaining the native conformation of the proteins; base consisting of: Caprylic/Capric triglyceride; PEG-18 castor oil dideate; Propylene glycol; Pentaerythrityl tetra Di-T-Benzyl hydroxy hydrocinnamate; tocopherol, Trisisopropanolamine that promotes the interactions by intermolecular forces with the domains of proteins making the structure thermodynamically more stable; and butylhydroxytoluene (BHT), which acts as an antioxidant, largely avoiding phenomena of chemical degradation by oxidation in proteins.
  • grape seed oil that creates a medium which reduces the electrostatic interactions with the protein residues while maintaining the native conformation of the proteins
  • base consisting of: Caprylic/Capric triglycer
  • inter-position process of protein with the oily phase components is carried out with appropriate quality; such a process is preferably carried out in clean rooms, under laminar flow conditions, where environmental quality controls as well as microbiological controls are guaranteed to ensure the sterility of the product.
  • the present invention proposes the development of a method for the preservation, storage and stabilization of proteins which contemplates an anhydrous dispersion phase (i.e., in the absence of water) with environmental and microbiological quality, through the application of oily substances having hydrophilic residues that guarantee interactions with the proteins that keep its conformation in the native state, constituting a reproducible, simple and economic method with regard to others methods that require the use of devices, complex methods and qualified personnel.

Abstract

A method for preserving and stabilising proteins is disclosed which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products, particularly cell growth factors and/or proteins such as epidermal growth factor (EGF) and fibroblast growth factor (bFGF). The method includes a dispersion phase, under normal pressure and temperature conditions, in which the proteins are incorporated into an anhydrous medium formed by oily components that have hydrophilic residues and that guarantee interactions with the proteins, while maintaining the native conformation of the proteins, such components being grape seed oil, a base of different components and butylhydroxytoluene.

Description

    OBJECT OF THE INVENTION
  • The invention, as stated the title of the present specification, relates to a method for preserving and stabilising proteins, which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products.
  • The object of the invention is focused on a method which envisages the creation of a dispersed system as a means for preservation, stabilization and storage of proteins in an oily phase under normal pressure and temperature conditions. Particularly, the method proposed by the invention is based on the incorporation of proteins, such as cell growth factors such as tales epidermal growth factor (EGF) and fibroblast growth factor (bFGF), although not limited thereto, in a medium composed of components, such as grape seed oil, a base consisting of various compounds that will be specified later in the present description, and butylhydroxytoluene (BHT), that form the cited oily phase. In particular, the method proposed takes advantage of some chemical groups of the oily phase components promote certain physical-chemical interactions with the residues of proteins that enhance for longer periods of time the maintenance of the native molecular structure of proteins, achieving that such method is simple, economical and of general application, with potential capacity to replace complex preservation techniques and/or aqueous means commonly used for the preservation of proteins.
    • FIELD OF THE INVENTION
  • The field of application of the present invention falls within the industrial chemical sector, focusing particularly on the scope of the industry dedicated to the manufacture of pharmaceutical and cosmetic products, in particular those intended to preserve growth factors.
    • BACKGROUND OF THE INVENTION
  • Currently the stability in proteins has attracted considerable interest in the chemical, pharmaceutical and cosmetic field. Proteins are used as active substances of numerous treatments in diseases such as diabetes, cancer, haemophilia, myocardial infarction, just to cite some pathologies [Krishnamurthy and Manning, 2002]. Note that the use of protein structures such as growth factors, e.g. the EGF, aroused a great interest in the cosmetic industry in recent years. So, if a protein can not be properly stabilized, it may lose its native structure with consequent loss of its biological activity [Krishnamurthy and Manning, 2002].
  • The problem is that the protein stabilization is particularly difficult since they are very susceptible to degradation phenomena: physical, chemical and enzymatic. Chemical degradation is related to deamination, oxidation, reduction, hydrolysis processes and chemical interactions such as disulfide bond interactions. Physical degradation includes surface adsorption, aggregation, dissociation, denaturation, and photolysis processes. In addition, there are factors that influence the aggregation of proteins related to the properties of the dispersion medium, such as temperature (related to the thermodynamics and kinetics of transformation of the structural protein conformation), pH (related to interactions of positive or negative charges with the protein residues), ionic strength (related to salts and their concentration to interact with charged groups) and surfactants (related to conformational thermodynamic stability) [Chi et al., 2003].
  • There are technological processes to ensure that proteins remain for longer period of time with its native conformation, said processes can be carried out by physical processes such as freezing (below −10° C.) or lyophilisation (for the elimination of the humidity present in an aqueous solution of protein), however, even the products obtained by these methods suffer from degradation; or chemical processes through the addition of co-solvents may be carried out [Chang and Pikal, 2009].
  • The EGF was the first polypeptide isolated and characterized as a growth factor. It has a biological activity related to its native structure capable of stimulating the proliferation of keratinocytes and fibroblasts (with the consequent formation of collagen), induces angiogenesis (formation of new vessels) and performs subsequent vascularisation of the area where it is applied. These properties promote the appearance of new skin with a considerable thick, restoring its elasticity and firmness, thus diminishing the unwanted effects of cellular oxidation and therefore resulting in the elimination of wrinkles [Tang et al., 1994]. Such growth factor has begun to use recently in topical formulations, where very good results have been obtained related to tissue regeneration, the acceleration in the healing of burns, treatment of keloid, acne and stretch marks, even improving outcomes of treatments of surgical type, promotion of the consolidation of skin grafts as well as the post-peeling application. However, said proteins are increasingly used in the pharmaceutical and cosmetic industry, but have not been used massively due to its high prices and their difficult stabilisation [Schouest et al., 2012].
  • Fibroblast growth factor (bFGF) is a growth factor that acts to increase the mitotic activity index and DNA synthesis, facilitating the proliferation of various precursor cells, such as chondroblasts, collagenoblasts, and osteoblasts, etc., that form the body's fibrous, connective, and support tissues. It contributes to wound healing, haematopoiesis, angiogenesis, or the embryonic development. To this end, they perform very different functions: a) they contribute to the re-epithelialisation of the tissues damaged during healing; b) they have blood vessel formation inducing-activity; c) they are involved in processes for differentiation of the blood cell lines; and, d) they are involved in the differentiation of skeletal and cardiac muscle, the maturation of the lungs and the specification of the hepatocytes from endoderm cells.
  • The object of the present invention is, therefore, the development of a new method for preserving and stabilising proteins, which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products that, unlike conventional methods, it takes place in oily phase so that it is more simple and economical, having noted that, at least by the applicant, the existence of any document or invention that discloses a method for preserving and stabilising proteins or similar invention that has technical characteristics similar to those here proposed is unaware.
    • EXPLANATION OF THE INVENTION
  • A medium for dispersing proteins the components of which provides the medium with an oily character has been developed. Thus, the EGF, bFGF and other cell growth factors and/or proteins, as stated, are macromolecules with difficult stabilization, since, currently, the majority of dispersion means have aqueous character and achieve the stabilization in a short period of time, through the use of dispersed systems such as emulsions, or expensive and very specific methods that do not ensure a longer life of the protein native structure, such as lyophilisation.
  • With the present invention, the development of the EGF and other growth factors and/or proteins has been carried out in oily medium as an intermediate product for use in specific industrial processes, promoting the stability of proteins with respect to the currently existing methods thus achieving a more effective action to the not denatured proteins in such medium not being denatured the proteins in such medium.
  • More specifically, according to the method of the present invention, in the formulation the growth factors are surrounded by an anhydrous medium composed of other components that act as adjuvants interacting with the residues of proteins, such components being: grape seed oil, that creates a medium which reduces the electrostatic interactions with the protein residues while maintaining the native conformation of the proteins; base consisting of: Caprylic/Capric triglyceride; PEG-18 castor oil dideate; Propylene glycol; Pentaerythrityl tetra Di-T-Benzyl hydroxy hydrocinnamate; tocopherol, Trisisopropanolamine that promotes the interactions by intermolecular forces with the domains of proteins making the structure thermodynamically more stable; and butylhydroxytoluene (BHT), which acts as an antioxidant, largely avoiding phenomena of chemical degradation by oxidation in proteins.
  • Note that the inter-position process of protein with the oily phase components is carried out with appropriate quality; such a process is preferably carried out in clean rooms, under laminar flow conditions, where environmental quality controls as well as microbiological controls are guaranteed to ensure the sterility of the product.
  • In short and succinctly, the present invention proposes the development of a method for the preservation, storage and stabilization of proteins which contemplates an anhydrous dispersion phase (i.e., in the absence of water) with environmental and microbiological quality, through the application of oily substances having hydrophilic residues that guarantee interactions with the proteins that keep its conformation in the native state, constituting a reproducible, simple and economic method with regard to others methods that require the use of devices, complex methods and qualified personnel.
  • Having sufficiently described the nature of the present invention, as well as a way of putting it into practice, it is not considered necessary to make a more extensive explanation in order that any expert in this area will understand its scope and the advantages that can be derived from it, making known that, within reason it could be put into practice in other embodiments differing in detail from that indicated by way of example, and which will obtain the same degree of protection, provided that they do not alter, change, or modify its fundamental principle.
    • BIBLIOGRAPHY
    • Chang L L, Pikal M J. Mechanisms of Protein Stabilization in the Solid State. J. Pharm. Sci. 98; 2009: 2886-2908.
    • Chi E Y, Krishnan S, Randolph T W, Carpenter J F. Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation. Pharm Res. 2003; 20: 1325-36.
    • Krishnamurthy R, Manning M C. The stability factor: importance in formulation development. Curr Pharm Biotechnol. 2002; 3: 361-71.
    • Schouest J M, Lun T K, Moy R L. Improved texture and appearance of barley produced, synthetic, human-like epidermal growth factor (EGF) serum. J. Drugs Dermatol. 2012; 11 (5): 613-620.
  • Tang Z, Zhang Z, Zheng Y et al. Cell aging of human diploid fibroblasts is associated with changes in responsiveness to epidermal growth factor and changes in HER-2 expression. Mechanisms of Ageing and Development 1994; 73 (1): 57-67

Claims (5)

1. Method for preserving and stabilising proteins, which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products, particularly cell growth factors and/or proteins, such as the epidermal growth factor (EGF) and fibroblast growth factor (bFGF), characterised in that it comprises a dispersion phase, under normal pressure and temperature conditions, in which the proteins are incorporated into an anhydrous medium formed by oily components having hydrophilic residues and guarantee interactions with the proteins while maintaining the native conformation of the proteins.
2. Method for preserving and stabilising proteins, which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products, according to claim 1, characterized in that the oily phase components comprise grape seed oil.
3. Method for preserving and stabilising proteins, which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products, according to claim 1, characterised in that the oily phase components comprise abase consisting of Caprylic/Capric triglyceride; PEG-18 castor oil dideate; Propylene glycol; Pentaerythrityl tetra Di-T-Benzyl hydroxy hydrocinnamate; tocopherol, Trisisopropanolamine.
4. Method for preserving and stabilising proteins, which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products, according to claim 1, characterised in that the oily phase components comprise butylhydroxytoluene.
5. Method for preserving and stabilising proteins, which can be used for the industrial development of formulations of sanitary, pharmaceutical and cosmetic products, according to claim 1, characterised in that the oily phase components are grape seed oil, butylhydroxytoluene and a base consisting of: Caprylic/Capric triglyceride; PEG-18 castor oil dideate; Propylene glycol; Pentaerythrityl tetra Di-T-Benzyl hydroxy hydrocinnamate; tocopherol, Trisisopropanolamine.
US14/759,320 2013-09-25 2014-09-23 Method for preserving and stabilising proteins, which can be used for industrial development of formulations of sanitary, pharmaceutical and cosmetic products Abandoned US20160030584A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
ESP201331394 2013-09-25
ES201331394A ES2502691B1 (en) 2013-09-25 2013-09-25 Protein preservation and stabilization method, applicable for industrial developments of medical, pharmaceutical and cosmetic formulations
PCT/ES2014/000151 WO2015011308A1 (en) 2013-09-25 2014-09-23 Method for preserving and stabilising proteins, which can be used for industrial development of formulations of sanitary, pharmaceutical and cosmetic products

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/ES2014/000151 A-371-Of-International WO2015011308A1 (en) 2013-09-23 2014-09-23 Method for preserving and stabilising proteins, which can be used for industrial development of formulations of sanitary, pharmaceutical and cosmetic products

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/855,338 Continuation-In-Part US20180193467A1 (en) 2013-09-23 2017-12-27 Method for preserving and stabilizing proteins for formulations of sanitary, pharmaceutical and cosmetic products

Publications (1)

Publication Number Publication Date
US20160030584A1 true US20160030584A1 (en) 2016-02-04

Family

ID=51626311

Family Applications (3)

Application Number Title Priority Date Filing Date
US14/759,320 Abandoned US20160030584A1 (en) 2013-09-25 2014-09-23 Method for preserving and stabilising proteins, which can be used for industrial development of formulations of sanitary, pharmaceutical and cosmetic products
US15/855,338 Abandoned US20180193467A1 (en) 2013-09-23 2017-12-27 Method for preserving and stabilizing proteins for formulations of sanitary, pharmaceutical and cosmetic products
US16/411,782 Active US11147882B2 (en) 2013-09-23 2019-05-14 Method for preserving and stabilizing proteins for formulations of sanitary, pharmaceutical and cosmetic products

Family Applications After (2)

Application Number Title Priority Date Filing Date
US15/855,338 Abandoned US20180193467A1 (en) 2013-09-23 2017-12-27 Method for preserving and stabilizing proteins for formulations of sanitary, pharmaceutical and cosmetic products
US16/411,782 Active US11147882B2 (en) 2013-09-23 2019-05-14 Method for preserving and stabilizing proteins for formulations of sanitary, pharmaceutical and cosmetic products

Country Status (11)

Country Link
US (3) US20160030584A1 (en)
EP (2) EP4241783A1 (en)
JP (1) JP6959002B2 (en)
KR (1) KR20160055720A (en)
CN (2) CN117402206A (en)
BR (1) BR112015020658B1 (en)
CA (1) CA2913394A1 (en)
ES (1) ES2502691B1 (en)
MX (1) MX2016001476A (en)
RU (1) RU2642277C2 (en)
WO (1) WO2015011308A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105055265A (en) * 2015-07-21 2015-11-18 北京博士园科技发展有限公司 Product capable of maintaining beauty and keeping young and preparation method of product

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020064509A1 (en) * 2000-10-03 2002-05-30 Sabine Grimm Method for producing a goniochromatic effect comprising applying to skin a cosmetic composition comprising at least one continuous lipophilic phase and at least one goniochromatic pigment

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3998753A (en) * 1974-08-13 1976-12-21 Hoffmann-La Roche Inc. Water dispersible carotenoid preparations and processes thereof
GB8604983D0 (en) * 1986-02-28 1986-04-09 Biocompatibles Ltd Protein preservation
US4806343A (en) * 1986-03-13 1989-02-21 University Of Southwestern Louisiana Cryogenic protectant for proteins
US5416242A (en) * 1992-09-25 1995-05-16 Nippon Hypox Laboratories Incorporated Hydroquinone derivative
US6267985B1 (en) * 1999-06-30 2001-07-31 Lipocine Inc. Clear oil-containing pharmaceutical compositions
KR100366439B1 (en) * 2000-02-21 2003-01-09 주식회사 대웅 Stable Pharmaceutical Composition Comprising Epidermal Growth Factor as an Active Ingredient
AU3664102A (en) * 2000-12-01 2002-06-11 Battelle Memorial Institute Method for stabilizing biomolecules in liquid formulations
ES2232305B1 (en) * 2003-11-07 2006-07-16 Miguel Angel Palomo S.A. PROCEDURE FOR OBTAINING TEXTURIZED AND THERMOSTABLE FOODS FROM NATURAL RAW MATERIALS AND PRODUCTS OBTAINED FROM THE SAME.
DK1768500T3 (en) * 2004-06-25 2011-06-27 Ferrosan As Compositions suitable for treating cutaneous signs of aging
US20080102128A1 (en) * 2006-07-28 2008-05-01 Flamel Technologies, Inc. Modified-release microparticles based on amphiphilic copolymer and on active principles(s) and pharmaceutical formulations comprising them
FR2910318B1 (en) * 2006-12-20 2009-07-03 Flamel Technologies Sa DISPERSION OF POLYAMINOACIDS IN A CONTINUOUS LIPID PHASE
ES2319061B1 (en) * 2007-09-11 2010-02-10 Biomedal, S.L. METHOD OF CONSERVATION OF PEPTIDES OR PROTEINS.
US20110020519A1 (en) * 2008-01-04 2011-01-27 Aveka, Inc. Encapsulation of oxidatively unstable compounds
IL188647A0 (en) * 2008-01-08 2008-11-03 Orina Gribova Adaptable structured drug and supplements administration system (for oral and/or transdermal applications)
EP3210474B1 (en) * 2008-09-17 2020-11-18 Chiasma, Inc. Pharmaceutical compositions comprising polypeptides and related methods of delivery

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020064509A1 (en) * 2000-10-03 2002-05-30 Sabine Grimm Method for producing a goniochromatic effect comprising applying to skin a cosmetic composition comprising at least one continuous lipophilic phase and at least one goniochromatic pigment

Also Published As

Publication number Publication date
US20190290770A1 (en) 2019-09-26
BR112015020658B1 (en) 2023-12-05
CN105209476A (en) 2015-12-30
ES2502691A1 (en) 2014-10-03
CN117402206A (en) 2024-01-16
EP4241783A1 (en) 2023-09-13
US20180193467A1 (en) 2018-07-12
JP6959002B2 (en) 2021-11-02
MX2016001476A (en) 2016-07-12
ES2502691B1 (en) 2015-07-07
US11147882B2 (en) 2021-10-19
CA2913394A1 (en) 2015-01-29
RU2016107313A (en) 2017-09-04
WO2015011308A1 (en) 2015-01-29
BR112015020658A2 (en) 2017-07-18
EP3050894A4 (en) 2017-04-19
KR20160055720A (en) 2016-05-18
EP3050894A1 (en) 2016-08-03
RU2642277C2 (en) 2018-01-24
JP2017501206A (en) 2017-01-12

Similar Documents

Publication Publication Date Title
JP6847080B2 (en) Composition for skin whitening or wrinkle improvement
CN108699519A (en) The stem cell-derived allochthon containing the raised growth factor
EP2745849B1 (en) Polydeoxyribonucleotides composition and uses thereof
KR20070089907A (en) Fetal skin cell protein compositions for the treatment of skin conditions, disorders or diseases and methods of making and using the same
CN105228590A (en) To comprise the functional cosmetic composition that somatomedin and aminoacid are feature
CN105543161B (en) Composite bio-active factor liposome and preparation method thereof
Shi et al. Bioactive glass activates VEGF paracrine signaling of cardiomyocytes to promote cardiac angiogenesis
US20160030584A1 (en) Method for preserving and stabilising proteins, which can be used for industrial development of formulations of sanitary, pharmaceutical and cosmetic products
CN115698264A (en) Method for preparing culture medium containing high-level high-efficiency exosomes secreted by umbilical cord blood stem cells and application thereof
KR20110139644A (en) Cosmetic composition comprising human stem cell conditioned media extracts in supercritical liposome as active ingredient
KR20230121973A (en) Preparation Process for Polynucleotide Fragments from Plant and Non-Aqueous Composition containing the same
KR101047873B1 (en) Cosmetic composition comprising human stem cell conditioned media extracts in supercritical liposome as active ingredient
JP2009507046A (en) Lopap-based pharmaceutical composition and use thereof
KR20190126619A (en) Anti-wrinkle composition comprising functional peptides and fibroblast conditioned medium
KR20190045829A (en) Method for improving transdermal delivery of exosome and its application
JP2014214094A (en) Cosmetic composition containing liposome including culture solution extract of stem cells derived from human
KR102600182B1 (en) Cosmetic composition containing human cord blood cell conditioned media exosome, glutathione, PDRN, and sodium hyaluronate, and manufacturing method thereof
KR102655943B1 (en) Composition for enhancing skin elasticity or improving skin wrinkles
KR102620622B1 (en) Cosmetic composition containing EGF with improved storage stability.
KR102540969B1 (en) Composition for promoting skin-regeneration containing sodium 2-mercaptoethane sulfonate
JP2010006734A (en) Skin care preparation for external use comprising growth factor, and bioproduct and its preservation method
CN112888483A (en) Skin-beautifying gene expression promoter
KR20120083166A (en) Enriched media of human adipose tissue-derived stem cells having skin elastic maintenance or antiaging effect and uses thereof
CN108578354A (en) A kind of skin fibroblasts transdermal formulation system care method
EA030842B1 (en) Stable cosmetic composition based on immobilized hyaluronidase and preparation method thereof

Legal Events

Date Code Title Description
AS Assignment

Owner name: SANI-RED, S.L., SPAIN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:MAYAYO FALO, TEODORO;REEL/FRAME:036866/0773

Effective date: 20150930

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION