CA2565944A1 - Stabilized hyaluronan preparations and related methods - Google Patents

Stabilized hyaluronan preparations and related methods Download PDF

Info

Publication number
CA2565944A1
CA2565944A1 CA002565944A CA2565944A CA2565944A1 CA 2565944 A1 CA2565944 A1 CA 2565944A1 CA 002565944 A CA002565944 A CA 002565944A CA 2565944 A CA2565944 A CA 2565944A CA 2565944 A1 CA2565944 A1 CA 2565944A1
Authority
CA
Canada
Prior art keywords
hyaluronan
polyglycol
range
composition according
peg
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.)
Granted
Application number
CA002565944A
Other languages
French (fr)
Other versions
CA2565944C (en
Inventor
Hampar L. Karageozian
John Park
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.)
SK Pharmaceuticals Inc
Original Assignee
S.K. Pharmaceuticals, Inc.
Hampar L. Karageozian
John Park
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 S.K. Pharmaceuticals, Inc., Hampar L. Karageozian, John Park filed Critical S.K. Pharmaceuticals, Inc.
Publication of CA2565944A1 publication Critical patent/CA2565944A1/en
Application granted granted Critical
Publication of CA2565944C publication Critical patent/CA2565944C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/04—Artificial tears; Irrigation solutions

Abstract

Stabilized hyaluronan preparations wherein hyaluronan is combined with a polyglycol, such as polyethylene glycol. Stabilized hyaluronan preparations of this invention may maintain their viscosity and lubricity for extended time periods (e.g., 2 years) without requiring refrigeration or special storage conditions.

Claims (40)

1. A composition comprising hyaluronan in combination with a polyglycol.
2. A composition according to claim 1 wherein the polyglycol comprises polyethylene glycol.
3. A composition according to claim 1 wherein the polyglycol has an average molecular weight in the range of about 200 to about 35,000.
4. A composition according to claim 1 wherein the polyglycol has an average molecular weight in the range of about 6000 to about 8000.
5. A composition according to claim 1 wherein the polyglycol comprises PEG.
6. A composition according to claim 5 wherein the PEG has an average molecular weight in the range of about 200 to about 35,000.
7. A composition according to claim 5 wherein the PEG has an average molecular weight in the range of about 6000 to about 8000.
8. A composition according to claim 5 wherein the PEG has an average molecular weight of about 8000.
9. A composition according to claim 1 wherein the hyaluronan comprises the sodium salt of hyaluronic acid.
10. A composition according to claim 1 wherein the hyaluronan has an average molecular weight in the range of about 2 × 10 3 to about 5 × 10 6.
11. A composition according to claim 1 wherein the hyaluronan has an average molecular weight in the range of about 2 × 10 5 to about 3 × 10 6.
12. A composition according to claim 1 wherein the weight ratio of hyaluronan to polyglycol is from about 0.1:1 to about 10:1.
13. A composition according to claim 1 wherein the weight ratio of hyaluronan to polyglycol is from about 1:2 to about.1:10.
14. A composition according to claim 1 wherein the concentration of hyaluronan is in the range of from about 0.01% by weight to about 10% by weight.
15. A composition according to claim 1 wherein the composition has a pH
in the range of about 5.0 to about 9.5.
16. A composition according to claim 1 wherein the composition has a pH
of about 7.2 - 7.4.
17. A composition according to claim 1 wherein the preparation is a solution having a tonicity in the range of about 200mOsm to about 340mOsm.
18. A composition according to claim 1 having the formula:

Hyaluronic Acid Sodium Salt ~0.10 - 6.0%
Polyethyleneglycol (PEG ~~0.50 - 30.0%
8000) Boric Acid ~~~~0.20%
Sodium Chloride ~~~0.58%
Postassium Chloride ~~0.14%
Calcium Chloride Dihydrate ~0.02%
Magnesium Chloride ~~~0.011%
Hexahydrate Sodium Chorite/Hydrogen ~~0.06 - 0.10%
Peroxide Purified Water Q.S ~~~to 100 mL.
19 A composition according to claim 1 having the formula;

Hyaluronic Acid Sodium Salt ~about 0.15%
Polyethyleneglycol (PEG ~~about 0.5%
8000) Boric Acid ~~~~about 0.2%
Sodium Chloride ~~~about 0.58%
Postassium Chloride ~~about 0.14%
Calcium Chloride Dihydrate ~about 0.02%
Magnesium Chloride ~~~about 0.11%
Hexahydrate Sodium Chorite/Hydrogen ~~about 0.06%
Peroxide Purified Water Q.S ~~~to 100 mL.
20. A method for manufacturing a hyaluronan preparation, said method comprising the step of:
A) combining the hyaluronan with a polyglycol.
21. A method according to claim 20 wherein the relative amounts of hyaluronan and polyglycol are selected to provide a preparation having a desired hyaluronan concentration wherein the hyaluronan substantially retains its viscosity and lubricious properties for at least a desired time period.
22. A method according to claim 21 wherein the desired time period is 2 years.
23. A method according to claim 20 wherein the hyaluronan comprises the sodium salt of hyaluronic acid.
24. A method according to claim 20 wherein the polyclycol comprises PEG.
25. A method according to claim 24 wherein the PEG has an average molecular weight in the range of about 200 to about 35,000.
26. A method according to claim 24 wherein the PEG has an average molecular weight in the range of about 6000 to about 8000.
27. A method according to claim 24 wherein the PEG has an average molecular weight of about 8000.
28. A method according to claim 20 wherein Step A comprises combining the hyaluronan and polyglycol in relative amounts and under conditions that cause the hyaluronan to react with the polyglycol to form a hyaluronan-polyglycol complex.
29. A method according to claim 20 wherein the hyaluronan has an average molecular weight in the range of from about 2 × 10 3 to about 5 × 10 6.
30. A method according to claim 20 wherein the hyaluronan has an average molecular weight in the range of from about 2 × 10 5 to about 3 × 10 6.
31. A method according to claim 20 wherein the weight ratio of hyaluronan to polyglycol is from about 1:5 to about 1:10.
32. A method according to claim 20 wherein the weight ratio of hyaluronan to polyglycol is from about 1:5 to about 1:10.
33. A method according to claim 20 wherein the composition has a pH in the range of about 5.0 to about 9.5.
34. A method according to claim 20 further comprising the step of:
B) adjusting the pH of the preparation to a desired pH.
35. A method according to claim 20 further comprising the step of:
B) adjusting the tonicity of the preparation to be in the range of about 200mOsm to about 340mOsm.
36. A method according to claim 20 wherein Step A comprises combining:

Hyaluronic Acid Sodium Salt ~0.10 - 6.0%
Polyethyleneglycol (PEG ~~0.50 - 30.0%
8000) Boric Acid ~~~~0.20%
Sodium Chloride ~~~0.58%
Postassium Chloride ~~0.14%
Calcium Chloride Dihydrate ~0.02%
Magnesium Chloride ~~0.011%
Hexahydrate Sodium Chorite/Hydrogen ~~0.06 - 0.10%
Peroxide Purified Water Q.S ~~~to 100 mL.
37. A method according to claim 20 wherein Step A comprises combining:

Hyaluronic Acid Sodium Salt ~about 0.15%
Polyethyleneglycol (PEG ~~about 0.5%
8000) Boric Acid ~~~~about 0.2%
Sodium Chloride ~~~about 0.58%
Postassium Chloride ~~about 0.14%
Calcium Chloride Dihydrate ~about 0.02%
Magnesium Chloride ~~about 0.11%
Hexahydrate Sodium Chorite/Hydrogen ~~about 0.06%
Peroxide Purified Water Q.S ~~~to 100 mL.
38. A method according to claim 20 wherein the concentration of hyaluronan is in the range of from about 0.01% by weight to about 10% by weight.
39. A method for treating a disease or ophthalmologic disorder in a human or animal subject comprising the step of administering to the subject, by an effective route or administration, a therapeutically effective amount of a preparation that comprises hyaluronan combined with a polyglycol.
40. The use of hyaluronan and at least one polyglycol in the manufacture of a preparation that is effective to treat a disease or disorder in a human or animal subject.
CA2565944A 2004-05-07 2005-05-09 Stabilized hyaluronan preparations and related methods Active CA2565944C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US56940704P 2004-05-07 2004-05-07
US60/569,407 2004-05-07
PCT/US2005/016271 WO2005110439A2 (en) 2004-05-07 2005-05-09 Stabilized hyaluronan preparations and related methods

Publications (2)

Publication Number Publication Date
CA2565944A1 true CA2565944A1 (en) 2005-11-24
CA2565944C CA2565944C (en) 2011-07-19

Family

ID=35394663

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2565944A Active CA2565944C (en) 2004-05-07 2005-05-09 Stabilized hyaluronan preparations and related methods

Country Status (7)

Country Link
US (1) US7544671B2 (en)
EP (1) EP1746884A4 (en)
JP (1) JP2007536277A (en)
AU (1) AU2005244059A1 (en)
CA (1) CA2565944C (en)
MX (1) MXPA06013056A (en)
WO (1) WO2005110439A2 (en)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070104798A1 (en) 1999-10-04 2007-05-10 S.K. Pharmaceuticals, Inc. Synergistic antimicrobial preparations containing chlorite and hydrogen peroxide
FR2850282B1 (en) 2003-01-27 2007-04-06 Jerome Asius INJECTABLE IMPLANT BASED ON CERAMIC FOR THE FILLING OF WRINKLES, CUTANEOUS DEPRESSIONS AND SCARS, AND ITS PREPARATION
US20070031467A1 (en) * 2005-08-04 2007-02-08 Abrahams John M Composition and method for vascular embolization
US20070031468A1 (en) * 2005-08-04 2007-02-08 Endomedix, Inc. Modified chitosan for vascular embolization
TW200733993A (en) * 2005-11-03 2007-09-16 Reseal Internat Ltd Partnership Continuously sealing one way valve assembly and fluid delivery system and formulations for use therein
US20080075657A1 (en) * 2006-04-18 2008-03-27 Abrahams John M Biopolymer system for tissue sealing
US20070243130A1 (en) * 2006-04-18 2007-10-18 Weiliam Chen Biopolymer system for tissue sealing
US7854923B2 (en) * 2006-04-18 2010-12-21 Endomedix, Inc. Biopolymer system for tissue sealing
US20080124395A1 (en) * 2006-06-22 2008-05-29 Weiliam Chen Formulations and devices for treatment or prevention of neural ischemic damage
BRPI0714587A2 (en) 2006-07-25 2013-05-07 Osmotica Corp aqueous ophthalmic sulfur and use of nesna
DE102006049580A1 (en) * 2006-10-20 2008-04-24 Rochel, Michael, Dr. med. Topical composition for the treatment of eczema
WO2009006130A2 (en) * 2007-06-28 2009-01-08 Bausch & Lomb Incorporated Salt free hyaluronate ophthalmic solution
CN102209548A (en) * 2008-09-15 2011-10-05 博士伦公司 Compositions comprising polymers having amino sugar units and methods of making and using same
WO2010125069A1 (en) * 2009-04-28 2010-11-04 Pharmasurgics In Sweden Ab Hyaluronic acid for preventing post surgical adhesions
IT1394223B1 (en) 2009-05-15 2012-06-01 Thea Sas Lab KIT FOR ASSESSMENT AND CUSTOMIZED SELECTION OF ARTIFICIAL TEARS
US8455436B2 (en) 2010-12-28 2013-06-04 Depuy Mitek, Llc Compositions and methods for treating joints
US8524662B2 (en) 2010-12-28 2013-09-03 Depuy Mitek, Llc Compositions and methods for treating joints
US8398611B2 (en) 2010-12-28 2013-03-19 Depuy Mitek, Inc. Compositions and methods for treating joints
DE102011077393A1 (en) * 2011-06-10 2012-12-13 Johannes Reinmüller Antiinfective agent
US8623839B2 (en) 2011-06-30 2014-01-07 Depuy Mitek, Llc Compositions and methods for stabilized polysaccharide formulations
KR101383941B1 (en) * 2012-03-09 2014-04-10 동아에스티 주식회사 Stable pharmaceutical composition containing piroxicam or its pharmaceutical acceptable salt and hyaluronic acid and its pharmaceutical acceptable salt and their manufacturing method thereof
PT3019177T (en) 2013-07-10 2020-12-30 Matrix Biology Inst Compositions of hyaluronan with high elasticity and uses thereof
US9682099B2 (en) 2015-01-20 2017-06-20 DePuy Synthes Products, Inc. Compositions and methods for treating joints
PL3352766T3 (en) 2015-09-24 2021-08-02 Matrix Biology Institute High elasticity hyaluronan compositions and methods of use thereof
EP3231417B1 (en) * 2016-04-15 2018-12-05 Dr. Gerhard Mann Chem.-Pharm. Fabrik GmbH Storage stable, ophthalmic compound
DE102018124022A1 (en) 2018-09-28 2020-04-02 Rheinisch-Westfälische Technische Hochschule (Rwth) Aachen HYALURONIC ACID STABILIZER
US10517988B1 (en) 2018-11-19 2019-12-31 Endomedix, Inc. Methods and compositions for achieving hemostasis and stable blood clot formation

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4629623A (en) * 1984-06-11 1986-12-16 Biomatrix, Inc. Hyaluronate-poly (ethylene oxide) compositions and cosmetic formulations thereof
JPS6479103A (en) * 1987-06-09 1989-03-24 Lion Corp External preparation
US5141741A (en) * 1988-12-09 1992-08-25 Lion Corporation Anti-sunburn skin-care preparation
JPH05170641A (en) * 1991-12-25 1993-07-09 Shiseido Co Ltd Cosmetic
JPH09227385A (en) * 1996-02-29 1997-09-02 Ofutekusu:Kk Adjuvant for ophthalmic operation
JPH1072376A (en) * 1996-09-02 1998-03-17 Ofutekusu:Kk Eye drop aqueous solution comprising hyaluronic acid
JPH10290830A (en) * 1997-04-18 1998-11-04 Ofutekusu:Kk Adjuvant for operating on eye
TWI285644B (en) * 1997-07-11 2007-08-21 Toray Industries A stable pharmaceutical composition containing a derivative of 4,5-epoxymorphinan and a water-soluble antioxidant, an oil-soluble antioxidant, a synergist, a sugar and a surfactant
CA2366880C (en) * 1999-04-02 2013-02-12 Fziomed, Inc. Compositions of polyacids and polyethers and methods for their use in reducing adhesions
JP2001019611A (en) * 1999-07-08 2001-01-23 Pola Chem Ind Inc Skin composition for external use
JP2004514778A (en) * 2000-11-28 2004-05-20 フォーカル　インコーポレーティッド Polyalkylene glycol viscosity enhancing polymer formulation
JP2002193815A (en) * 2000-12-25 2002-07-10 Ophtecs Corp Eye drops for prevention of corneal drying for ophthalmic operation
FR2825273B1 (en) * 2001-05-29 2006-11-24 Oreal COMPOSITION FOR THE TREATMENT OF SKIN SIGNS OF AGING
US20030203030A1 (en) * 2002-01-18 2003-10-30 Control Delivery Systems, Inc. Polymeric gel delivery system for pharmaceuticals
JP4263456B2 (en) * 2002-03-18 2009-05-13 わかもと製薬株式会社 Hyaluronic acid-containing thermal gelled preparation
US20040137079A1 (en) * 2003-01-08 2004-07-15 Cook James N. Contact lens and eye drop rewetter compositions and methods
US20040185068A1 (en) * 2003-03-18 2004-09-23 Zhi-Jian Yu Self-emulsifying compositions, methods of use and preparation

Also Published As

Publication number Publication date
WO2005110439A2 (en) 2005-11-24
JP2007536277A (en) 2007-12-13
US7544671B2 (en) 2009-06-09
MXPA06013056A (en) 2007-04-17
US20060029571A1 (en) 2006-02-09
CA2565944C (en) 2011-07-19
EP1746884A2 (en) 2007-01-31
WO2005110439A3 (en) 2006-05-11
AU2005244059A1 (en) 2005-11-24
EP1746884A4 (en) 2010-01-13

Similar Documents

Publication Publication Date Title
CA2565944A1 (en) Stabilized hyaluronan preparations and related methods
KR930000861B1 (en) Omeprazole rectal composition
CY1123084T1 (en) TREATMENT OF GLYCOGEN STORAGE DISEASE TYPE II
KR101182496B1 (en) Transparent eye drops containing latanoprost
TW200727903A (en) Stable pharmaceutical compositions of 5, 10 methylenetetrahydrofolate
TW200639159A (en) Treatment of pain
AU2008222592B2 (en) Compositions and methods for delivery of anti-cancer agents
WO2007056263A3 (en) Methods of treating cancer with high potency lipid-based platinum compound formulations administered intravenously
EP1177791A3 (en) Use of glycogen phosphorylase inhibitors to inhibit tumor growth
JP2014237607A (en) Composition for injection comprising pemetrexed
CA2529441A1 (en) Use of hyaluronic acid for preparing compositions for treating oral cavity aphthas
JPH115744A (en) Aqueous solution preparation for external use containing hyaluronic acid
US20120231053A1 (en) Block Copolymer For Intraperitoneal Administration Containing Anti-Cancer Agent, Micelle Preparation Thereof, And Cancer Therapeutic Agent Comprising The Micelle Preparation As Active Ingredient
US8367636B2 (en) Composition based on salts of hyaluronic acid for treating epithelial lesions
JPH0674212B2 (en) Method for preventing contraindications for aqueous formulations containing benzalkonium chloride
JP4442118B2 (en) Stable eye drops
JPH075456B2 (en) Eye drops
EP3701938B1 (en) Ophthalmic formulations based on atropine
CO5021217A1 (en) STABLE COMPOSITIONS OF MITOXANTRONE, PROCEDURE TO PREPARE THEM; USE OF SUCH COMPOSITIONS AND MEDICATIONS THAT INCLUDE SUCH SOLUTIONS FOR THE TREATMENT OF CANCER DISEASES
MXPA05008711A (en) Use of r-10-hydroxy-10, 11-dihydro-carbamazepine in neuropathic pain.
CN102215819B (en) Pharmaceutical composition having relatively low ionic strength
JP3694868B2 (en) Sodium hyaluronate injection composition
JP5984531B2 (en) Aqueous ophthalmic composition
WO1997024374A1 (en) Stable solution containing sodium hyaluronate
IE870569L (en) Stable injection composition

Legal Events

Date Code Title Description
EEER Examination request