WO2007013100A1 - Gel formulation comprising platelet derived growth factor - Google Patents
Gel formulation comprising platelet derived growth factor Download PDFInfo
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- WO2007013100A1 WO2007013100A1 PCT/IN2006/000265 IN2006000265W WO2007013100A1 WO 2007013100 A1 WO2007013100 A1 WO 2007013100A1 IN 2006000265 W IN2006000265 W IN 2006000265W WO 2007013100 A1 WO2007013100 A1 WO 2007013100A1
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- gel formulation
- formulation according
- pharmaceutical gel
- pharmaceutical
- viscosity
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- 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
- A61K38/1858—Platelet-derived growth factor [PDGF]
Definitions
- the present invention is in the field of Biotechnology more specifically bio- pharmaceutical preparation for better wound healing.
- a skin wound is defined as a breach in the continuity of any body tissue caused by a minimal direct injury to the skin.
- Acute wounds like cuts, bruises or incisions follow a relatively short normal healing process of Inflammation, fibro proliferation and scar formation while Chronic Wounds like pressure ulcers, burns, diabetic ulcers, arterial or venous ulcers are suspended in repetitive cycles of inflammation and fibroproliferation leading to delayed healing.
- Chronic, non-healing wounds have plagued healthcare practitioners for decades and quick closure of the wounded skin is often a much desired clinical outcome.
- Platelet derived growth factor and more specifically the BB homodimer (PDGF-BB) has been shown to be active in promoting wound healing in several animal and human trials.
- Human platelet-derived growth factor has been shown to be the major mitogenic protein in serum for mesenchymal derived cells.
- rhPDGF-BB platelet extracts or purified Recombinant Human Platelet Derived Growth Factor (rhPDGF-BB) induces either cell multiplication or DNA synthesis in cultured smooth muscle cells, fibroblasts and glial cells.
- rhPDGF BB is a potent chemo attractant for cells that are responsive to it as a mitogen. This is also somewhat unusual in that mitogens generally do not also act as chemo tactic agents.
- rhPDGF-BB has therapeutic applications for the treatment of injuries which require the proliferation of fibroblasts or smooth muscle cells to heal.
- rhPDGF-BB has been shown to be active in promoting wound healing in several animal models.
- Lynch et al disclose the use of insulin like growth factor and purified PDGF- BB to promote healing of dermal wound in pigs.
- Lynch et al also found that combination PDGF-BB and IGF-I promotes bone and cementum formation in a dog model of periodontitis.
- Greenhalgh et al demonstrated enhanced healing of full-thickness skin wounds in genetically diabetic mice treated with recombinant PDGF-BB as compared to control animals.
- Thomason et al disclose that recombinant PDGF-BB accelerates the gain in tensile strength of healing skin wounds in rats and promotes wound healing in diabetic rats. rhPDGF-BB has also subsequently been found to promote healing in diabetic foot ulcers in several multi centric human clinical trials and is now being used for this indication around the world.
- Hyaluronic acid is a polysachharide present in connective tissues of all vertebrates, specially occurring in high proportions in cartilage, umbilical cord, skin, vitreous body and synovial fluid.
- hyaluronic acid is the main macromolecular component of the ground substance, where it accounts for about 55% of the content.
- Hyaluronic acid interacts with proteoglycans to makeup complex macromolecular matrix in which hyaluronic acid forms the "backbone".
- An important property of hyaluronic acid is its interaction with water which results a highly amorphous network, which is needed for the selective diffusion of solutes, the passage of water, and respiration process. This ground substance helps for the organization of vascular, fibrillar and cellular structures.
- Guar galactomannan (more commonly known as guar gum) consists chiefly of a high molecular weight hydrocolloidal polysaccharide, composed of galactan and mannan units combined through glycoside linkages, which may be described chemically as galactomannan. It is commonly used in cosmetics, food products, and pharmaceutical formulations. It is used as suspending agent; tablet binder; tablet disintegrant; thickening agent; viscosity increasing agent and also as controlled-release carrier. Therapeutically, guar has also been used as part of the diet of patients with diabetes mellitus.
- Gelatin is widely used in a variety of pharmaceutical formulations and applications, including its use as biodegradable matrix material in an implantable delivery system. It is commonly used as coating agent; film former; gelling agent suspending agent; tablet binder; viscosity increasing agent. Gelatin is also used in microencapsulation of drugs, where the active drug is sealed inside a microsized capsule or beadlet, which may then be handled as a powder. Therapeutically, gelatin has been used in the preparation of wound dressings and has been used as a plasma substitute. Gelatin is also widely used in food products and photographic emulsions. Commercially available gel formulations comprising of rhPDGF-BB presently use cellulose polymers like carboxymethylcellulose.
- US Patent 5,457,093 cited here as a reference mentions an invention using these cellulose polymers amongst a base composed of other excipients that help the stability of the PDGF gel.
- US Patent 5,457,093 makes no mention of the storage conditions of the said invention.
- Most proteins, peptides and other biological molecules are generally susceptible to higher temperatures or drastic variations in temperature and hence the preferred long term storage condition for most biological molecules is at temperatures between 2-8° c. At temperatures between 2-8° c the nature of the cellulose polymer based gels remain optimal for the long periods of time.
- the present invention provides a new improved aqueous gel formulation capable of retaining the viscosity despite short term variations in the temperature and storage conditions without loss of the desired stability of the molecule necessary for providing optimal healing.
- This said composition comprises of rhPDGF-BB, Hyaluronic acid and /or carboxymethylcellulose; protein stabilizers like gelatin, other gel stabilizing agents like guar galactomannan and buffers where in the maximum mitogenic activity of rhPDGF-BB is retained when drug product is stored at room temperatures between to 20-40 0 C for short periods of time usually a period not extending beyond 8 weeks.
- the present composition also provides a stable aqueous gel without significant change in viscosity at these temperatures.
- the definition of 'Stability' in this regard also refers to the prevention of loss of mitogenic activity of the PDGF in the gel or an increase in the amount of PDGF protein that is released from the gel.
- the gel formulations of the present invention provide a better consistency and are also easily adhering and provide a better moist environment for the wound at room temperature of around 40° C.
- the gel also has the ability to absorb wound exudates thereby promoting wound healing.
- the present invention provides a new improved aqueous gel formulation capable of retaining the viscosity despite short term variations in the temperature storage conditions without loss of the desired stability of the molecule necessary for providing optimal healing.
- Viscosity is a measure of the resistance of a liquid to flow and is defined as the ratio of the shearing stress to the rate of shearing.
- the viscosity is represented in centipoise (cps) and is measured using a Viscometer like that by Brookfield. All viscosity values are at room temperature e.g. 22°- 25° C unless indicated.
- the present aqueous gel composition contains water soluble, pharmaceutically accepted polymeric material (s) and provides a viscosity in the range 50,000-200,000 cps at room temperature.
- Temperature is the amount of thermal energy or heat in a system and is a physical property of a system which underlies the common notions of "hot” and "cold”; the material with the higher temperature is said to be hotter.
- the Celsius scale for the measurement of temperature in which 0 °C corresponds to the temperature at which water freezes and 100 °C corresponds to the boiling point of water at sea level. This is usually measured with a calibrated glass instrument filled with mercury called as the thermometer.
- the gel formulations in the present invention have the advantage of having bio degradable, natural materials having good viscosity at low concentrations and ability to retain this viscosity despite variations in the room temperatures and also of easily adhering to the wound of different sizes and shapes.
- the present invention relates to improved formulation of PDGF-BB using hyaluronic acid, and/or carboxy methyl cellulose and/or guar gum wherein desired viscosity and stability of the active ingredient is achieved.
- the formulation also includes stabilizers and buffers to maintain long-term stability at the desired pH environment.
- Hyaluronic acid and all other components are added and left overnight for better hydration and solubilisation of the components.
- Parabens were dissolved separately and mixed with others before adding PDGF-BB. After 24 hours rhPDGF-BB is added and again mixed well and the gel is stored at 4-10°C. The viscosity and stability studies are performed at room temperature and at 40°C with a relative humidity of 70%. The activity and integrity of PDGF-BB in new formulation is monitored by cell proliferation assay using human fibroblast cells and SDS-PAGE analysis respectively.
- Example 1 By the procedure described above a gel composition is prepared using the following constituents
- the new formulations showed better consistency, viscosity over a wide range of temperature 4-40 0 C. Viscosity values were around 100,000 cps and the gel stability was also better for around two months at 40 0 C.
- the PDGF-BB activity was analyzed by fibroblast cell proliferation assay and was found to be 1x10 6 for the same period indicating that PDGF-BB is stable in the present formulation. SDS-PAGE analysis was also indicated the 35kD band intact and in accordance with the concentration before and after formulation.
- the present formulations are very smooth gels and the spreading on the wounds easily when applied.
Abstract
A new improved pharmaceutical gel formulation comprising of Platelet Derived Growth Factor (PDGF) hyaluronic acid and/or carboxymethylcellulose and/or guar galactomannan and protein stabilizers like gelatin; buffer salts and other preservatives capable of retaining viscosity at room temperature despite variations in the storage temperatures for short periods of time without the loss of the desired stability of the molecule for providing optimal wound healing.
Description
Field of the invention: Gel formulation comprising platelet derived growth factor
The present invention is in the field of Biotechnology more specifically bio- pharmaceutical preparation for better wound healing.
Background of the invention:
A skin wound is defined as a breach in the continuity of any body tissue caused by a minimal direct injury to the skin. Acute wounds like cuts, bruises or incisions follow a relatively short normal healing process of Inflammation, fibro proliferation and scar formation while Chronic Wounds like pressure ulcers, burns, diabetic ulcers, arterial or venous ulcers are suspended in repetitive cycles of inflammation and fibroproliferation leading to delayed healing. Chronic, non-healing wounds have plagued healthcare practitioners for decades and quick closure of the wounded skin is often a much desired clinical outcome.
In this regard Platelet derived growth factor (PDGF) and more specifically the BB homodimer (PDGF-BB) has been shown to be active in promoting wound healing in several animal and human trials. Human platelet-derived growth factor has been shown to be the major mitogenic protein in serum for mesenchymal derived cells. A number of studies reported that platelet extracts or purified Recombinant Human Platelet Derived Growth Factor (rhPDGF-BB) induces either cell multiplication or DNA synthesis in cultured smooth muscle cells, fibroblasts and glial cells. Furthermore rhPDGF BB is a potent chemo attractant for cells that are responsive to it as a mitogen. This is also somewhat unusual in that mitogens generally do not also act as chemo tactic agents.
rhPDGF-BB has therapeutic applications for the treatment of injuries which require the proliferation of fibroblasts or smooth muscle cells to heal. In this regard rhPDGF- BB has been shown to be active in promoting wound healing in several animal models. Lynch et al disclose the use of insulin like growth factor and purified PDGF- BB to promote healing of dermal wound in pigs. Lynch et al also found that combination PDGF-BB and IGF-I promotes bone and cementum formation in a dog model of periodontitis. In addition Greenhalgh et al demonstrated enhanced healing of full-thickness skin wounds in genetically diabetic mice treated with recombinant
PDGF-BB as compared to control animals. Thomason et al disclose that recombinant PDGF-BB accelerates the gain in tensile strength of healing skin wounds in rats and promotes wound healing in diabetic rats. rhPDGF-BB has also subsequently been found to promote healing in diabetic foot ulcers in several multi centric human clinical trials and is now being used for this indication around the world.
Hyaluronic acid is a polysachharide present in connective tissues of all vertebrates, specially occurring in high proportions in cartilage, umbilical cord, skin, vitreous body and synovial fluid. In human dermis, hyaluronic acid is the main macromolecular component of the ground substance, where it accounts for about 55% of the content. Hyaluronic acid interacts with proteoglycans to makeup complex macromolecular matrix in which hyaluronic acid forms the "backbone". An important property of hyaluronic acid is its interaction with water which results a highly amorphous network, which is needed for the selective diffusion of solutes, the passage of water, and respiration process. This ground substance helps for the organization of vascular, fibrillar and cellular structures.
Guar galactomannan (more commonly known as guar gum) consists chiefly of a high molecular weight hydrocolloidal polysaccharide, composed of galactan and mannan units combined through glycoside linkages, which may be described chemically as galactomannan. It is commonly used in cosmetics, food products, and pharmaceutical formulations. It is used as suspending agent; tablet binder; tablet disintegrant; thickening agent; viscosity increasing agent and also as controlled-release carrier. Therapeutically, guar has also been used as part of the diet of patients with diabetes mellitus.
Gelatin is widely used in a variety of pharmaceutical formulations and applications, including its use as biodegradable matrix material in an implantable delivery system. It is commonly used as coating agent; film former; gelling agent suspending agent; tablet binder; viscosity increasing agent. Gelatin is also used in microencapsulation of drugs, where the active drug is sealed inside a microsized capsule or beadlet, which may then be handled as a powder. Therapeutically, gelatin has been used in the preparation of wound dressings and has been used as a plasma substitute. Gelatin is also widely used in food products and photographic emulsions.
Commercially available gel formulations comprising of rhPDGF-BB presently use cellulose polymers like carboxymethylcellulose. US Patent 5,457,093 cited here as a reference mentions an invention using these cellulose polymers amongst a base composed of other excipients that help the stability of the PDGF gel. However US Patent 5,457,093 makes no mention of the storage conditions of the said invention. Most proteins, peptides and other biological molecules are generally susceptible to higher temperatures or drastic variations in temperature and hence the preferred long term storage condition for most biological molecules is at temperatures between 2-8° c. At temperatures between 2-8° c the nature of the cellulose polymer based gels remain optimal for the long periods of time.
However in developing countries like India the patients suffering from chronic ulcers that need the use of rhPDGF-BB are often from low socioeconomic status and frequently do not own proper facilities for storage. As the treatment period for using this product usually ranges between 2-8 weeks, during these periods they are dependent on the hospitals with facilities for storage further adding to the overall burden of treatment. Further, this problem is compounded by the fact that in tropical countries like India the peak room temperatures often go beyond 40° C and this can present a problem for the stability of the biological molecules if appropriate storage conditions are not maintained. Without the proper storage conditions the product containing cellulose polymers has a tendency to drop in viscosity and 'liquefy' making the application of a specified quantity of the rhPDGF-BB difficult. Infact another critical aspect of the usage of rhPDGF-BB formulations is the usage of a specific quantity of rhPDGF-BB for achieving the optimal healing effect.
In order to prevent the formulation from liquefying and to protect the integrity and retain the stability and viscosity of the product despite short term variations in the storage conditions there is a need for a new formulation that will achieve this.
References
Ross et. al Proc. Natl. Acad. Sci. USA. 71; 1207, 1974 Kohler and Lipton, Exp. Cell Res. 87:297, 1974 Ross etal J. Biol. Chem 257:5154, 1982
Grotendorst et al. J Cell Physiol. 113:261, 1982
Seppa et.al. J. Cell Biol, 92:584, 1982
Lynch et al Proc. Natl. Acad. Sci. USA 84:7696-7700, 1987
Lynch et al J Clin Periodontal 16:545-548, 1989
Greebhalgh et al AmJ.Pathol 136:1235-1246, 1990
Thomason et al EPO :282,317 A2
Ettlin et al, United States Patent 6005075, 1999.
Ettlin et al, European Patent Application No. 0 679 718 A2. 1995.
Beldarrain et al., Biotechnol Appl. Biochem. (2001) 33, 173-182.
Swaminathan and Khanna, Protein Expression and Purification, (1999) 15, 263-242.
Thatcher and Panayotatos, Methods Enzymol. (1986) 119, 166-177.
Tamowski et al., Methods Enzymol. (1986) 119, 153-165.
Haelewyn and Dey Bio. And MoI. Biology Int. 37(6) 1163-1171, 1995
Arora and Khanna, J. of Biotech. 52, 127-133, 1996
Emlen J Woodruff and Vlasselaer Peter Van US Pat 2001043906 2001-11-22
Ebbesen et al US pat. 5540923, 1996 July 30.
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Vandenbroeck et al. EJB 213, 481-486, 1993
Khuller et al ., Indian JPharm Sci 1999; 61(6): 342-345
Feinstein and Bartilucci. JPharm Sci. 1966; 55:332-334
Sakr and Elasbbagh. Pharm Ind 1977; 39(4):399-403.
Adkin et al., Pharm Res 1997; 14(l):103-107.
Wong et al., J Control Release 1997; 47:173-179
Jenkins et al Lancet 1977; II: 779-780.
Uusitupa MIJ. Br. Med. J. 301 (6743):122.
Fan H and Dash AK. IntJPharm 2001:13;103-116
Armstrong et al. J Pharm Pharmacol 1982:34(suppl) 5P
Tu et al. Drug Dev Ind Pharm 2001 :27(7):687-692.
Ridgeway, K. Hard Capsules: Development and Technology, London.
Pharmaceutical Press, 1987. Kimura et al. Chem Pharm Bull 1991:39; 1328-1329.
Thomas S., Wound Management and Dressings. London: Pharmaceutical Press 1990. Blanloeil et al. Therapie. 1983; 38:539-546. US Patent 5,457,093 US Patent 5705485
Summary of the invention
The present invention provides a new improved aqueous gel formulation capable of retaining the viscosity despite short term variations in the temperature and storage conditions without loss of the desired stability of the molecule necessary for providing optimal healing. This said composition comprises of rhPDGF-BB, Hyaluronic acid and /or carboxymethylcellulose; protein stabilizers like gelatin, other gel stabilizing agents like guar galactomannan and buffers where in the maximum mitogenic activity of rhPDGF-BB is retained when drug product is stored at room temperatures between to 20-400C for short periods of time usually a period not extending beyond 8 weeks. The present composition also provides a stable aqueous gel without significant change in viscosity at these temperatures. The definition of 'Stability' in this regard also refers to the prevention of loss of mitogenic activity of the PDGF in the gel or an increase in the amount of PDGF protein that is released from the gel.
The gel formulations of the present invention provide a better consistency and are also easily adhering and provide a better moist environment for the wound at room temperature of around 40° C. The gel also has the ability to absorb wound exudates thereby promoting wound healing.
Detailed Description of the Invention
The present invention provides a new improved aqueous gel formulation capable of retaining the viscosity despite short term variations in the temperature storage conditions without loss of the desired stability of the molecule necessary for providing optimal healing.
Viscosity is a measure of the resistance of a liquid to flow and is defined as the ratio of the shearing stress to the rate of shearing. The viscosity is represented in centipoise (cps) and is measured using a Viscometer like that by Brookfield. All viscosity values are at room temperature e.g. 22°- 25° C unless indicated. The present aqueous gel composition contains water soluble, pharmaceutically accepted polymeric material (s) and provides a viscosity in the range 50,000-200,000 cps at room temperature.
Temperature is the amount of thermal energy or heat in a system and is a physical property of a system which underlies the common notions of "hot" and "cold"; the
material with the higher temperature is said to be hotter. For everyday applications, it is often convenient to use the Celsius scale for the measurement of temperature in which 0 °C corresponds to the temperature at which water freezes and 100 °C corresponds to the boiling point of water at sea level. This is usually measured with a calibrated glass instrument filled with mercury called as the thermometer.
The gel formulations in the present invention have the advantage of having bio degradable, natural materials having good viscosity at low concentrations and ability to retain this viscosity despite variations in the room temperatures and also of easily adhering to the wound of different sizes and shapes.
In one aspect the present invention relates to improved formulation of PDGF-BB using hyaluronic acid, and/or carboxy methyl cellulose and/or guar gum wherein desired viscosity and stability of the active ingredient is achieved. The formulation also includes stabilizers and buffers to maintain long-term stability at the desired pH environment.
The invention is better defined by processes of the formulation and the examples given below.
Hyaluronic acid and all other components are added and left overnight for better hydration and solubilisation of the components. Parabens were dissolved separately and mixed with others before adding PDGF-BB. After 24 hours rhPDGF-BB is added and again mixed well and the gel is stored at 4-10°C. The viscosity and stability studies are performed at room temperature and at 40°C with a relative humidity of 70%. The activity and integrity of PDGF-BB in new formulation is monitored by cell proliferation assay using human fibroblast cells and SDS-PAGE analysis respectively.
The following examples are described here explaining the preferred embodiments of the present invention by way of illustrating the invention. However this does not limit the scope of the present invention in any way.
Example 1
By the procedure described above a gel composition is prepared using the following constituents
PDGF-BB lO mg
Hyaluronic acid sodium salt 1000 mg
Carboxymethyl Cellulose 100 mg
Methyl paraben 160 mg
Propyl paraben 20 mg
NaCl 850 mg
Sodium acetate 160 mg
Acetic acid to adjust pH to 6.0
Water for injection Made up to 100 g
Example 2
By the procedure described above a gel composition is prepared using the following constituents
PDGF-BB 10 mg
Hyaluronic acid sodium salt 1500 mg
Carboxymethyl Cellulose 500 mg
Methyl paraben 160 mg
Propyl paraben 20 mg
NaCl 850 mg
Sodium acetate 160 mg
Acetic acid to adjust pH to 6.0
Water for injection Made up to 100 g
Example 3
By the procedure described above a gel composition is prepared using the following constituents
PDGF-BB 10 mg
Hyaluronic acid sodium salt 2400 mg
Methyl paraben 160 mg
Propyl paraben 20 mg
NaCl 850 mg
Sodium acetate 160 mg
Acetic acid to adjust pH to 6.0
Water for injection Made up to 100 g
Example 4
By the procedure described above a gel composition is prepared using the following constituents
PDGF-BB lO mg
Hyaluronic acid sodium salt 2000 mg
Guar gum 500 mg
Methyl paraben 160 mg
Propyl paraben 20 mg
NaCl 850 mg
Sodium acetate 160 mg
Acetic acid to adjust pH to 6.0
Water for injection Made up to . 100 g
Example 5
By the procedure described above a gel composition is prepared using the following constituents
PDGF-BB 10 mg
Hyaluronic acid sodium salt 2000 mg
Guar gum 500 mg
Gelatin 100 mg
Methyl paraben 160 mg
Propyl paraben 20 mg
NaCl 850 mg
Sodium acetate 160 mg
Acetic acid to adjust pH to 6.0
Water for injection Made up to 100 g
Results
Quantitatively, the new formulations showed better consistency, viscosity over a wide range of temperature 4-400C. Viscosity values were around 100,000 cps and the gel stability was also better for around two months at 400C. The PDGF-BB activity was analyzed by fibroblast cell proliferation assay and was found to be 1x106 for the same period indicating that PDGF-BB is stable in the present formulation. SDS-PAGE analysis was also indicated the 35kD band intact and in accordance with the concentration before and after formulation. The present formulations are very smooth gels and the spreading on the wounds easily when applied.
Claims
1. A pharmaceutical gel formulation comprising of
a. An effective amount of pharmaceutically acceptable platelet derived growth factor (PDGF);
b. A pharmaceutically acceptable natural polymer carrier base comprising of polysaccharide and/ or modified polysaccharides selected from a group comprising of hyaluronic acid and or guar galactomannan and or carboxymethylcellulose.
c. Protein stabilizers like pharmaceutically grade of gelatin and buffers salts and other preservatives
wherein the composition is capable of retaining viscosity in the range between 50,000 cps to 200,000 cps at room temperature despite variations in the storage temperatures in the range between 20-40° C for short periods of time ranging between 2 to 8 weeks without the loss of the desired stability of the molecule.
2. A pharmaceutical gel formulation according to claim 1, wherein the PDGF is ideally but not limited, to recombinant human platelet derived growth factor B-B homodimer (rhPDGF-BB).
3. A pharmaceutical gel formulation according to claim 1, wherein the viscosity is adjusted by adding varying amounts of hyaluronic acid in the concentrations ranging between 0.5.% to 2.5% with the an average molecular weight of the polymer ranging between 500 kilo daltons to about 5000 kilo daltons.
4. A pharmaceutical gel formulation according to claim 1, wherein the viscosity is adjusted by adding varying amounts of pharmaceutical grade guar galactomannan in the concentration ranging between 0.1 to 1.0%.
5. A pharmaceutical gel formulation according to claim 1 wherein concentration of pharmaceutical grade gelatin is within the range between 0.2%- 1.0 %.
6. A pharmaceutical gel formulation according to claim 1, wherein the pH is maintained between 4 to 8, preferably between 5 to 7 and more preferably at 6.0.
7. A pharmaceutical gel formulation according to claim 6, wherein the pH is adjusted by using buffer salts selected from the group of sodium phosphates, sodium acetates, sodium succinate and phosphoric acid, succinic acid and glacial acetic acid.
8. A pharmaceutical gel formulation according to claim 1, wherein the preservatives are selected from a group consisting of but not limited to methyl paraben and/or propyl paraben.
9. A pharmaceutical gel formulation according to claim 1, wherein the salts are selected from a group consisting of but not limited sodium chloride and/or potassium chloride.
Applications Claiming Priority (2)
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IN1008/CHE/2005 | 2005-07-26 | ||
IN1008CH2005 | 2005-07-26 |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008120085A2 (en) * | 2007-03-29 | 2008-10-09 | Adocia | Angiogenic composition |
US8241620B2 (en) | 2005-09-26 | 2012-08-14 | Adocia | Complex polymere amphiphile-PDGF |
WO2017118774A1 (en) * | 2016-01-04 | 2017-07-13 | Agencia Pública Empresarial Sanitaria Hospital De Poniente | Composition for use in the treatment of mucous membrane lesions using endoscopic resection |
US10071182B2 (en) | 2014-10-14 | 2018-09-11 | Samuel E. Lynch | Methods for treating wounds |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5705485A (en) * | 1987-09-18 | 1998-01-06 | Ethicon, Inc. | Gel formulations containing growth factors |
US5770228A (en) * | 1991-11-04 | 1998-06-23 | Zymogenetics, Inc. | Platelet derived growth factor gel formulation |
US5804213A (en) * | 1991-10-09 | 1998-09-08 | Lectec Corporation | Biologically active aqueous gel wound dressing |
US20040157073A1 (en) * | 2001-04-23 | 2004-08-12 | Nucryst Pharmaceuticals Corp., A Alberta, Canada Corporation | Lubricious coatings for substrates |
-
2006
- 2006-07-26 WO PCT/IN2006/000265 patent/WO2007013100A1/en active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5705485A (en) * | 1987-09-18 | 1998-01-06 | Ethicon, Inc. | Gel formulations containing growth factors |
US5804213A (en) * | 1991-10-09 | 1998-09-08 | Lectec Corporation | Biologically active aqueous gel wound dressing |
US5770228A (en) * | 1991-11-04 | 1998-06-23 | Zymogenetics, Inc. | Platelet derived growth factor gel formulation |
US20040157073A1 (en) * | 2001-04-23 | 2004-08-12 | Nucryst Pharmaceuticals Corp., A Alberta, Canada Corporation | Lubricious coatings for substrates |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8241620B2 (en) | 2005-09-26 | 2012-08-14 | Adocia | Complex polymere amphiphile-PDGF |
WO2008120085A2 (en) * | 2007-03-29 | 2008-10-09 | Adocia | Angiogenic composition |
WO2008120085A3 (en) * | 2007-03-29 | 2009-09-11 | Adocia | Angiogenic composition |
US10071182B2 (en) | 2014-10-14 | 2018-09-11 | Samuel E. Lynch | Methods for treating wounds |
WO2017118774A1 (en) * | 2016-01-04 | 2017-07-13 | Agencia Pública Empresarial Sanitaria Hospital De Poniente | Composition for use in the treatment of mucous membrane lesions using endoscopic resection |
US11147762B2 (en) | 2016-01-04 | 2021-10-19 | Agencia Pública Empresarial Sanitaria Hospital De | Composition for use in the treatment of mucous membrane lesions using endoscopic resection |
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