WO2008031196A1 - Treatment of aged skin with autologous growth factors in a hyaluronic acid delivery system - Google Patents
Treatment of aged skin with autologous growth factors in a hyaluronic acid delivery system Download PDFInfo
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- WO2008031196A1 WO2008031196A1 PCT/CA2007/001572 CA2007001572W WO2008031196A1 WO 2008031196 A1 WO2008031196 A1 WO 2008031196A1 CA 2007001572 W CA2007001572 W CA 2007001572W WO 2008031196 A1 WO2008031196 A1 WO 2008031196A1
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- Prior art keywords
- hyaluronic acid
- growth factors
- treatment
- autologous
- skin
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Definitions
- the present invention relates generally to anti-aging compositions and to the treatment of aged and photoaged skin with autologous growth factors. Such growth factors may be produced by autologous skin cell culture.
- Anti-aging compositions have been in use for years.
- anti-aging, growth factor compositions are comprised of skin growth factor cocktails derived from fetal and neonatal human cell cultures.
- the main problem with conventional anti-aging, growth factor compositions is that they are allogeneic in origin. Another problem with conventional anti-aging, growth factor compositions is that being allogeneic they may be incompatible with the recipient and therefore inactive. Another problem with conventional anti-aging, growth factor compositions is that being allogeneic they may be immunologically incompatible with the recipient which would obviate the possibility of delivery by injection. A further problem with conventional anti-aging, growth factor compositions is that they are not designed to deliver the growth factors to the treatment site. In these respects, the treatment of aged skin with autologous growth factors according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides a novel composition developed for the purpose of the treatment of aged and photoaged skin.
- the present invention provides a new treatment of aged and photoaged skin with autologous growth factors.
- growth factors may be produced by autologous skin cell culture.
- the general purpose of the present invention is to provide a new cosmetic composition and the use of the composition in a new treatment of aged and photoaged skin with autologous growth factors that have the advantages that the anti-aging compositions according to aspects of the invention, include novel features that result in a new treatment of aged skin with the autologous growth factors.
- the present invention generally comprises autologous growth factors and a delivery system that consists of a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid, its non-toxic salts (such as sodium salt) and combinations thereof and wherein the molecular weight of the form of hyaluronic acid is in the range of about 150,000 to about 750,000 daltons, sufficient to facilitate the penetration of the growth factors through the tissue at a site to be treated (including scar tissue) through the cell membranes into the individual cells to be treated.
- the molecular weight of the form of hyaluronic acid is in the range of between about 150,000 and about 750,000 daltons.
- a suitable combination may comprise autologous growth factors produced by cultured autologous skin cells and a hyaluronic acid- based delivery system. Additional features to the combination of the invention may be added which additional features may constitute different and additional inventions.
- a primary object of the present invention is to provide a treatment of aged and photoaged skin with autologous growth factors that will overcome the shortcomings of the prior art compositions.
- Another object of the present invention is to provide a treatment of aged and photoaged skin with autologous growth factors for the treatment of aged and photoaged skin with autologous growth factors.
- Such growth factors may be produced by autologous skin cell culture.
- Still another object of the invention is to provide a treatment of aged skin with autologous growth factors, with effective amounts taken from a composition comprising, for example, at least one extracted growth factor suitable for treatment of selected skin conditions wherein the growth factor is obtained from cultured, autologous skin cells and the amount of the form of the hyaluronic acid in the effective dosage form exceeds 10 mg.
- Still yet another object of the invention is to provide a treatment of aged and photoaged skin with autologous growth factors wherein the growth factor is one or more growth factors selected from the group of growth factors that include but are not limited to TGF-alpha, EGF, KGF, bFGF, SCF, ET-I , IGF-I .
- Another object is to provide a treatment of aged and photoaged skin with autologous growth factors with a composition as above wherein the growth factor is present in therapeutically effective concentrations.
- Another object is to provide a treatment of aged and photoaged skin with autologous growth factors which method of treatment comprises the steps of providing a monolayer culture of autologous skin cells (keratinocytes, melanocytes, fibroblasts) together with the form of hyaluronic acid on the portion of the skin to be treated.
- Another object is to provide a treatment of aged and photoaged skin with autologous growth factors.
- the method of treating the aged and photoaged skin comprising the step of contacting the skin with at least one growth factor, wherein the growth factor is obtained from cultured skin cells together with the form of hyaluronic acid on the portion of the skin to be treated.
- the form of hyaluronic acid applied with the growth factor for example, monolayer culture of autologous skin cells, to the skin comprises at least about 10 mg.
- Another object is to provide a treatment of aged skin by cryopreserving young autologous skin cells and/or autologous growth factors for as long as Is required.
- Another object is to provide a treatment of aged skin by combining autologous growth factors with the co-factors of antioxidants and their converting enzymes.
- Another object is to provide a treatment of aged skin with autologous growth factors, the method of treating aged and photoaged skin, wherein the growth factor(s) is combined with hyaluronic acid, for example medical grade, average molecular weight 700 kiloDaltons and/or salts thereof and/or homologues, analogues, derivatives, complexes, esters, fragments and subunits of hyaluronic acid is sufficient to facilitate the growth factor(s) deposition and penetration through the tissue (including scar tissue) at the site to be treated using an effective amount of the form of the hyaluronic acid (such as at least 10 mg of the form of hyaluronic acid) for each application.
- hyaluronic acid for example medical grade, average molecular weight 700 kiloDaltons and/or salts thereof and/or homologues, analogues, derivatives, complexes, esters, fragments and subunits of hyaluronic acid is sufficient to facilitate the growth factor(s) de
- a treatment of aged and photoaged skin with autologous growth factors which comprises autologous growth factors
- such treatment employs an effective amount of a form of hyaluronic acid (for example at least 10 mg of the form of hyaluronic acid) selected from the group consisting of hyaluronic acid, its non-toxic salts and combinations thereof and/or homologues, analogues, derivatives, complexes, esters, fragments and subunits of hyaluronic acid in one embodiment together with an effective amount of autologous growth factors sufficient to facilitate the penetration of the growth factors through the tissue at a site to be treated through the cell membranes into the individual cells to be treated, wherein in an embodiment the form of hyaluronic acid is hyaluronic acid or a salt thereof or a combination thereof where
- Growth factors include cytokines, proteins produced by a variety of cell types, which function to regulate cell growth, development and activation. Certain growth factors are known to promote dermal fibroblast and keratinocyte proliferation and to induce extracellular matrix formation including fibrellar collagen. In addition to their central role in wound healing, growth factors have been demonstrated to have beneficial effects in reducing the signs of skin aging. There are many growth factors that interact to re-establish a balanced homeostatic environment in aged and photoaged skin. These will include but are not limited to: TGF-alpha, EGF, KGF, bFGF, SCF, ET-I, IGF-I .
- the autologous growth factors are delivered to the skin by the use of a hyaluronic acid component. The autologous growth factors may also be delivered in conjunction with other delivery systems such as liposomes.
- Skin cells have been cultivated by a number of techniques.
- cultures of autologous skin cells are grown in monolayer culture by standard, well known, techniques. These cells produce extracellular proteins during cultivation.
- Autologous skin cells can be extracted and/or concentrated from skin cells.
- a so-called growth factor "cocktail" can be therapeutically used in the treatment of skin to visibly reverse the effects of aging and photoaging.
- the extraction purification and/or concentration of the growth factors according to the present invention can be accomplished by dialysis filtration which can be used to remove small molecular weight molecules from sera and other biological fluids.
- dialysis filtration or more commonly “ultrafiltration” uses hydrostatic pressure instead of concentration gradients to extract, concentrate and/or purify the growth factors described above from the supernatant and cells of a human skin cell culture.
- use of the growth factor compositions of the present invention includes contacting a growth factor composition of the present invention with aged or photoaged skin.
- growth factor treatment involves contacting an effective amount (including 10 mg of the form of hyaluronan) of a composition of the present invention with a defect in the skin.
- the defect can have resulted from injury, disease or trauma as well as age- related degeneration.
- the composition of the present invention comprises a growth factor "cocktail" with hyaluronan or its derivatives that can be contacted with the aged or photoaged skin or defects of the skin by topical application and/or by injection. An example of such a composition is set out below.
- the growth factor cocktail may comprise one or combinations of the following: TGF- alpha, EGF, KGF, bFGF, SCF, ET-I, IGF-I .
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Abstract
A composition for the treatment of aged and photoaged skin with autologous growth factors and the treatment of aged and photoaged skin with autologous growth factors (such growth factors may be produced by autologous skin cell culture); the treatment comprising administering a composition comprising autologous growth factors and a delivery system comprising an effective amount of a form of hyaluronic acid selected from hyaluronic acid, its non-toxic salt and combinations thereof, wherein said form of hyaluronic acid facilitates the penetration of the growth factors through the tissue in order to reach the individual cells to be treated. The molecular weight of the form of hyaluronic acid is in the range of about 150,000 to about 750,000 daltons. Autologous growth factors used for this invention are TGF-alpha, EGF, KGF, bFGF, SCF, ET-I, IGF-I and combinations thereof.
Description
TITLE OF THE INVENTION
Treatment of Aged Skm with Autologous Growth Factors in a Hyaluronic Acid Delivery System
BACKGROUND OF THE INVENTION Field of the Invention The present invention relates generally to anti-aging compositions and to the treatment of aged and photoaged skin with autologous growth factors. Such growth factors may be produced by autologous skin cell culture. Description of the Related Art
Anti-aging compositions have been in use for years. Typically, anti-aging, growth factor compositions are comprised of skin growth factor cocktails derived from fetal and neonatal human cell cultures.
The main problem with conventional anti-aging, growth factor compositions is that they are allogeneic in origin. Another problem with conventional anti-aging, growth factor compositions is that being allogeneic they may be incompatible with the recipient and therefore inactive. Another problem with conventional anti-aging, growth factor compositions is that being allogeneic they may be immunologically incompatible with the recipient which would obviate the possibility of delivery by injection. A further problem with conventional anti-aging, growth factor compositions is that they are not designed to deliver the growth factors to the treatment site. In these respects, the treatment of aged skin with autologous growth factors according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides a novel composition developed for the purpose of the treatment of aged and photoaged skin. SUMMARY OF THE INVENTION Unlike the foregoing disadvantages inherent in the known types of anti-aging, growth factor compositions now present in the prior art, the present invention provides a new treatment
of aged and photoaged skin with autologous growth factors. Such growth factors may be produced by autologous skin cell culture.
Thus, the general purpose of the present invention is to provide a new cosmetic composition and the use of the composition in a new treatment of aged and photoaged skin with autologous growth factors that have the advantages that the anti-aging compositions according to aspects of the invention, include novel features that result in a new treatment of aged skin with the autologous growth factors.
According to one aspect of the invention, the present invention generally comprises autologous growth factors and a delivery system that consists of a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid, its non-toxic salts (such as sodium salt) and combinations thereof and wherein the molecular weight of the form of hyaluronic acid is in the range of about 150,000 to about 750,000 daltons, sufficient to facilitate the penetration of the growth factors through the tissue at a site to be treated (including scar tissue) through the cell membranes into the individual cells to be treated. Preferably the molecular weight of the form of hyaluronic acid is in the range of between about 150,000 and about 750,000 daltons.
Thus, according to another aspect of the invention, a suitable combination may comprise autologous growth factors produced by cultured autologous skin cells and a hyaluronic acid- based delivery system. Additional features to the combination of the invention may be added which additional features may constitute different and additional inventions.
Thus, a primary object of the present invention is to provide a treatment of aged and photoaged skin with autologous growth factors that will overcome the shortcomings of the prior art compositions. Another object of the present invention is to provide a treatment of aged and photoaged
skin with autologous growth factors for the treatment of aged and photoaged skin with autologous growth factors. Such growth factors may be produced by autologous skin cell culture.
Still another object of the invention is to provide a treatment of aged skin with autologous growth factors, with effective amounts taken from a composition comprising, for example, at least one extracted growth factor suitable for treatment of selected skin conditions wherein the growth factor is obtained from cultured, autologous skin cells and the amount of the form of the hyaluronic acid in the effective dosage form exceeds 10 mg.
Still yet another object of the invention is to provide a treatment of aged and photoaged skin with autologous growth factors wherein the growth factor is one or more growth factors selected from the group of growth factors that include but are not limited to TGF-alpha, EGF, KGF, bFGF, SCF, ET-I , IGF-I .
Another object is to provide a treatment of aged and photoaged skin with autologous growth factors with a composition as above wherein the growth factor is present in therapeutically effective concentrations. Another object is to provide a treatment of aged and photoaged skin with autologous growth factors which method of treatment comprises the steps of providing a monolayer culture of autologous skin cells (keratinocytes, melanocytes, fibroblasts) together with the form of hyaluronic acid on the portion of the skin to be treated.
Another object is to provide a treatment of aged and photoaged skin with autologous growth factors. The method of treating the aged and photoaged skin comprising the step of contacting the skin with at least one growth factor, wherein the growth factor is obtained from cultured skin cells together with the form of hyaluronic acid on the portion of the skin to be treated. Preferably the form of hyaluronic acid applied with the growth factor, for example, monolayer culture of autologous skin cells, to the skin comprises at least about 10 mg. Another object is to provide a treatment of aged skin by cryopreserving young autologous
skin cells and/or autologous growth factors for as long as Is required.
Another object is to provide a treatment of aged skin by combining autologous growth factors with the co-factors of antioxidants and their converting enzymes.
Another object is to provide a treatment of aged skin with autologous growth factors, the method of treating aged and photoaged skin, wherein the growth factor(s) is combined with hyaluronic acid, for example medical grade, average molecular weight 700 kiloDaltons and/or salts thereof and/or homologues, analogues, derivatives, complexes, esters, fragments and subunits of hyaluronic acid is sufficient to facilitate the growth factor(s) deposition and penetration through the tissue (including scar tissue) at the site to be treated using an effective amount of the form of the hyaluronic acid (such as at least 10 mg of the form of hyaluronic acid) for each application.
Other objects and advantages of the present invention will become obvious to the reader and it is intended that these objects and advantages are within the scope of the present invention. DISCUSSION OF EMBODIMENTS OF THE INVENTION Turning now to a treatment of aged and photoaged skin with autologous growth factors, which comprises autologous growth factors, such treatment employs an effective amount of a form of hyaluronic acid (for example at least 10 mg of the form of hyaluronic acid) selected from the group consisting of hyaluronic acid, its non-toxic salts and combinations thereof and/or homologues, analogues, derivatives, complexes, esters, fragments and subunits of hyaluronic acid in one embodiment together with an effective amount of autologous growth factors sufficient to facilitate the penetration of the growth factors through the tissue at a site to be treated through the cell membranes into the individual cells to be treated, wherein in an embodiment the form of hyaluronic acid is hyaluronic acid or a salt thereof or a combination thereof wherein the molecular weight of the form of hyaluronic acid is in the range of about 150,000 to about 750,000 daltons and the autologous growth factors are preferably produced by
cultured autologous skin cells.
Growth factors include cytokines, proteins produced by a variety of cell types, which function to regulate cell growth, development and activation. Certain growth factors are known to promote dermal fibroblast and keratinocyte proliferation and to induce extracellular matrix formation including fibrellar collagen. In addition to their central role in wound healing, growth factors have been demonstrated to have beneficial effects in reducing the signs of skin aging. There are many growth factors that interact to re-establish a balanced homeostatic environment in aged and photoaged skin. These will include but are not limited to: TGF-alpha, EGF, KGF, bFGF, SCF, ET-I, IGF-I . The autologous growth factors are delivered to the skin by the use of a hyaluronic acid component. The autologous growth factors may also be delivered in conjunction with other delivery systems such as liposomes.
Skin cells have been cultivated by a number of techniques.
In one embodiment of the present invention, cultures of autologous skin cells are grown in monolayer culture by standard, well known, techniques. These cells produce extracellular proteins during cultivation.
Many biological compounds control skin cell development. Autologous skin cells can be extracted and/or concentrated from skin cells. In particular a monolayer culture of skin cells to form a growth factor composition, a so-called growth factor "cocktail" can be therapeutically used in the treatment of skin to visibly reverse the effects of aging and photoaging.
In one embodiment, the extraction purification and/or concentration of the growth factors according to the present invention can be accomplished by dialysis filtration which can be used to remove small molecular weight molecules from sera and other biological fluids. In the present invention, dialysis filtration, or more commonly "ultrafiltration" uses hydrostatic pressure instead of concentration gradients to extract, concentrate and/or purify the growth factors described
above from the supernatant and cells of a human skin cell culture.
In one embodiment, use of the growth factor compositions of the present invention includes contacting a growth factor composition of the present invention with aged or photoaged skin. In another embodiment, growth factor treatment involves contacting an effective amount (including 10 mg of the form of hyaluronan) of a composition of the present invention with a defect in the skin. The defect can have resulted from injury, disease or trauma as well as age- related degeneration. The composition of the present invention comprises a growth factor "cocktail" with hyaluronan or its derivatives that can be contacted with the aged or photoaged skin or defects of the skin by topical application and/or by injection. An example of such a composition is set out below.
Percentage (%)
(rounded to one decimal point)
Water 95.0
Sodium Hyaluronate 3.0
Growth Factor Cocktail 1.0
Phenoxyethanol 0.8
Methylparaben 0.2
100.0
The growth factor cocktail may comprise one or combinations of the following: TGF- alpha, EGF, KGF, bFGF, SCF, ET-I, IGF-I .
The foregoing is considered as illustrative only of the invention and is not to be interpreted in the limiting sense. Since numerous modifications and changes will readily occur to those skilled in the art, the invention is not limited to the exact description, and accordingly, all suitable modifications and equivalents, falling within the scope of the invention are incorporated herein.
Claims
1. Treatment of aged or photoaged skin with autologous growth factors for the treatment of aged and photoaged skin the treatment comprising administering a combination which includes autologous growth factors and a delivery system that consists of a sufficient effective amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid, its non-toxic salts and combinations thereof and/or homologues, analogues, derivatives, complexes, esters, fragments and subunits of hyaluronic acid sufficient to facilitate the penetration of the growth factors through the tissue at a site to be treated through the cell membranes into the individual cells to be treated.
2. The treatment of claim 1 wherein the form of hyaluronic acid is selected from hyaluronic acid, its non-toxic salts and combinations thereof.
3. The treatment of claim 1 or 2 wherein the form of hyaluronic acid has a molecular weight between about 150,000 and about 750,000 daltons.
4. The treatment of claim 1 , 2 or 3 wherein the sufficient effective amount of the form of hyaluronic acid comprises at least 10 mg.
5. The treatment of claim 1 , 2, 3 or 4 wherein autologous growth factors may be produced by cultured autologous skin cells and a hyaluronixc acid-based delivery system.
6. The treatment of claim 1, 2, 3 , 4 or 5 wherein the autologous growth factors are selected from TGF-alpha, EGF, KGF, bFGF, SCF, ET-I, IGF-I and combinations thereof.
7. The treatment of claim 1, 2, 3, 4, 5 or 6 wherein the autologous growth factors are combined with antioxidants and/or their converting enzymes.
8. The treatment of claim 1 , 2, 3, 4, 5, 6 or 7 wherein the combinations thereof are cryopreserved at the early stage of aging for the use of treating skin at the later stage of aging.
9. The combination of autologous growth factors and a delivery system that consists of a form of hyaluronic acid selected from the group consisting of hyaluronic acid, its non-toxic salts and combinations thereof and/or homologues, analogues, derivatives, complexes, esters, fragments and subunits of hyaluronic acid sufficient to facilitate the penetration of the growth factors through the tissue at a site to be treated through the cell membranes into the individual cells to be treated.
10. The combination of claim 9 wherein the form of hyaluronic acid selected from hyaluronic acid, its non-toxic salts and combinations thereof.
11. The combination of claim 9 or 10 wherein the molecular weight of the form of hyaluronic acid is from about 150,000 to about 750,000 daltons.
12. The combination of claim 9, 10 or 1 1 wherein autologous growth factors may be produced by cultured autologous skin cells and a hyaluronic acid-based delivery system.
13. The combination of claims 9, 10, 1 1 or 12 wherein the autologous growth factors are selected from TGF-alpha, EGF, KGF, bFGF, SCF, ET-I, IGF-I .
14. An effective amount of a combination for application to the skin of claim 9, 10, 11, 12 or 13 wherein the form of the hyaluronic acid comprises at least 10 mg and the autologous growth factors comprise an effective amount.
15. A formulation comprising about 95% water; 3% sodium hyaluronate; 1% growth factor; 0.8% phenoxyethanol; and 0.2% methylparaben.
16. The formulation of claim 13 wherein the growth factor is selected from TGF-alpha, EGF, KGF, bFGF, SCF, ET-I, IGF-I .
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84408406P | 2006-09-13 | 2006-09-13 | |
| US60/844,084 | 2006-09-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2008031196A1 true WO2008031196A1 (en) | 2008-03-20 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CA2007/001572 WO2008031196A1 (en) | 2006-09-13 | 2007-09-11 | Treatment of aged skin with autologous growth factors in a hyaluronic acid delivery system |
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| WO (1) | WO2008031196A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2263683A1 (en) * | 2008-03-28 | 2010-12-22 | Labo Juversa Co., Ltd. | Agent for treating skin aging and scars |
| US20130266536A1 (en) * | 2010-01-06 | 2013-10-10 | Ágústa Guõmundsdóttir | Method of use of stabilized plant-derived growth factor in skin care |
| CN108578265A (en) * | 2018-07-04 | 2018-09-28 | 广州领衔生物科技有限公司 | Maintenance stoste and its preparation method and application |
| WO2021186243A1 (en) * | 2020-03-19 | 2021-09-23 | Skingen International Inc. | Skin care compositions comprising 8 or more recombinant human growth factors and use thereof for reducing sings of aging |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2263683A1 (en) * | 2008-03-28 | 2010-12-22 | Labo Juversa Co., Ltd. | Agent for treating skin aging and scars |
| EP2263683A4 (en) * | 2008-03-28 | 2013-11-13 | Labo Juversa Co Ltd | Agent for treating skin aging and scars |
| US9023792B2 (en) | 2008-03-28 | 2015-05-05 | Labo Juversa Co., Ltd. | Method for treating keloid and hypertrophic scars by administration of bFGF |
| US20130266536A1 (en) * | 2010-01-06 | 2013-10-10 | Ágústa Guõmundsdóttir | Method of use of stabilized plant-derived growth factor in skin care |
| CN108578265A (en) * | 2018-07-04 | 2018-09-28 | 广州领衔生物科技有限公司 | Maintenance stoste and its preparation method and application |
| WO2021186243A1 (en) * | 2020-03-19 | 2021-09-23 | Skingen International Inc. | Skin care compositions comprising 8 or more recombinant human growth factors and use thereof for reducing sings of aging |
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