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WO1999000079A1 - Skin aging and wound treatment using cell migration agents - Google Patents

Skin aging and wound treatment using cell migration agents

Info

Publication number
WO1999000079A1
WO1999000079A1 PCT/US1998/013675 US9813675W WO9900079A1 WO 1999000079 A1 WO1999000079 A1 WO 1999000079A1 US 9813675 W US9813675 W US 9813675W WO 9900079 A1 WO9900079 A1 WO 9900079A1
Authority
WO
WIPO (PCT)
Prior art keywords
cell migration
indole
agent
dosage
migration agent
Prior art date
Application number
PCT/US1998/013675
Other languages
French (fr)
Original Assignee
Time Block, Inc.
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 Time Block, Inc. filed Critical Time Block, Inc.
Priority to JP50590299A priority Critical patent/JP2002504933A/en
Priority to EP98934222A priority patent/EP1009345A4/en
Priority to AU83797/98A priority patent/AU8379798A/en
Publication of WO1999000079A1 publication Critical patent/WO1999000079A1/en
Priority to US09/273,681 priority patent/US6174541B1/en

Links

Classifications

    • 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
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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 to a plant derived cell migration agent, such as Indole-3- Acetic acid, that facilitates the healing of tissue such as skin.
  • the cell migration agent is useful in treating wrinkled skin and can minimize the effects of photo aging on the skin by itself, or in conjunction with alpha-hydroxy acid (AHA), retinoic acid, or other chemical peel agents.
  • AHA alpha-hydroxy acid
  • retinoic acid or other chemical peel agents.
  • Human tissue can be damaged in numerous ways.
  • the skin can be burned by the sun or the application of acids such as alpha-hydroxy acid (AHA).
  • AHA alpha-hydroxy acid
  • Muscle tissue can suffer damage from a lack of oxygen or from traumatic injury. In either case, the body produces a certain healing response.
  • Cell migration agents generally promote the migration of fibroblast cells from the periphery of the wounded tissue to a location inside the wounded area.
  • Fibroblast cells are mesenchyme cells which give rise to connective tissue.
  • a wound includes any damage to tissue from any source.
  • the tissue such as skin, heals inward from the peripheral edge of the wound. Improved healing speed has been observed when fibroblast cells migrate to the middle of the wound and heal outward to meet the inward progression from the periphery.
  • Patent No. 5,188,655 to Jones et al. discloses a plant growth enhancing composition comprising as an active ingredient a synergistic mixture of (a) gibberellins, (b) the heteroauxin indole-3-
  • acetic acid and the cytokinin 6-(4-hydroxy-3-methyl-2trans-betenylamino) purine have very low molecular weights typically between 175 and 346. There has been no correlation between the use of plant growth hormones and wound healing in human cell studies. A need exists for a plant derived cell migration agent that can be used to improve the
  • Such a cell migration agent should be useful for human application with particular benefits in healing skin. Skin damage can include aging from sun or chemical exposure. Therefore, a suitable cell migration agent should be useful in minimizing or healing skin damage associated with aging and sun or chemical exposure.
  • Indole- 3-Acetic acid also known as "Auxin”
  • its derivatives significantly increases the migration of fibroblast cells at five days after treatment initiation.
  • Derivatives such as Indole-3-Acetyl-L- Phenylalanine have shown improved cell migration results.
  • derivatives such as Indole-
  • Auxin and its derivative Indole-3-Acetyl-L-Phenylalanine maintained increased migration rates throughout the study. When administered in a dosage of at least 0.1 ppm, these compounds appear to have the ability to move healthy human fibroblast cells into areas void of cells more rapidly than if the agent were not present. Dosage levels of between 2 and 250 ppm showed better results. Once migrated, the healthy cells can then divide at their normal rate thus effectively filling the voided area quicker. This results in the plumping of the skin or healing of
  • the compounds can be delivered by topical or internal methods of application.
  • Figure 1 is a bar chart showing the observed relative cell migration distances under the effect of three compounds under test for three days;
  • Figure 2 is a bar chart showing the observed relative cell migration distances under the effect of three compounds under test for five days;
  • Figure 3 is a bar chart showing the observed relative cell migration distances under the effect of three compounds under test for ten days;
  • Figure 4 is a bar chart showing the observed relative cell migration distances under the effect of three compounds under test for fourteen days.
  • Figure 5 is a bar chart showing the migration response of Agent B versus fibroblast growth factor.
  • Agent C was a compound containing gibberellic acid. Agent A was significantly inhibitory and agent B was mildly inhibitory of fibroblast cell growth. Fibroblasts are the chief cell of interest for these studies due to their central role in wound healing. Agent C had no significant influence on cell growth.
  • the agents could be administered by injection, topical application, ingestion or inhalation.
  • Treatment groups were statistically compared using Student's unpaired / - analysis.
  • the results as represented in Figures 1 to 4 indicate that agent B consistently and significantly increased fibroblast cell migration relative to cells treated with control media alone starting at day 5 after treatment initiation.
  • Cells treated with agent A also showed a small but significant increase in cell migration relative to control cells at days 5 and 14.
  • FGF fibroblast growth factor
  • agents A and B had significant effects to stimulate fibroblast cell migration.
  • the fact that these agents are not mitogenic may be a positive characteristic in terms of an agent that might be therapeutically applied.
  • a mitogenic agent might provoke concerns relative to its potential effects as a carcinogen.
  • the stimulation of migration by agents A and B raise the possibility that it may be an effective agent in promoting wound healing.
  • Agents A and B should reduce the signs of skin aging.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Birds (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
  • Indole Compounds (AREA)

Abstract

A cell migration agent promotes the healing of wounds by promoting movement of fibroblast cells away from the periphery of the wound. The agents can include Indole-3-Acetic acid and its derivatives such as Indole-3-Acetyl-L-Phenylalanine. Significant increases in the migration of fibroblast cells were observed at five days after treatment initiation. When administered in a dosage of between 0.1 and 250 ppm, these compounds appear to have the ability to move healthy human fibroblast cells into areas void of cells more rapidly than if the agent were not present. This results in the plumping of the skin or healing of wounds. The compounds can be delivered by topical or internal methods of application.

Description

SKIN AGING AND WOUND TREATMENT
USING CELL MIGRATION AGENTS
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a plant derived cell migration agent, such as Indole-3- Acetic acid, that facilitates the healing of tissue such as skin. The cell migration agent is useful in treating wrinkled skin and can minimize the effects of photo aging on the skin by itself, or in conjunction with alpha-hydroxy acid (AHA), retinoic acid, or other chemical peel agents.
BACKGROUND OF THE INVENTION
Human tissue can be damaged in numerous ways. For example, the skin can be burned by the sun or the application of acids such as alpha-hydroxy acid (AHA). Muscle tissue can suffer damage from a lack of oxygen or from traumatic injury. In either case, the body produces a certain healing response. It has been proposed that the speed of healing of tissue damage is improved with the application of a cell migration agent. Cell migration agents generally promote the migration of fibroblast cells from the periphery of the wounded tissue to a location inside the wounded area. Fibroblast cells are mesenchyme cells which give rise to connective tissue. For purposes of this discussion, a wound includes any damage to tissue from any source. During the normal healing process, the tissue, such as skin, heals inward from the peripheral edge of the wound. Improved healing speed has been observed when fibroblast cells migrate to the middle of the wound and heal outward to meet the inward progression from the periphery.
It has been proposed that the plant hormones or growth factors might also play an
important role in the healing of wounded animal tissue. Certain compounds appear to improve the growth of plant cells including gibberellins, indolacetic acid and kinetin. For example, U.S.
Patent No. 5,188,655 to Jones et al. discloses a plant growth enhancing composition comprising as an active ingredient a synergistic mixture of (a) gibberellins, (b) the heteroauxin indole-3-
acetic acid and the cytokinin 6-(4-hydroxy-3-methyl-2trans-betenylamino) purine. These plant growth enhancing agents have very low molecular weights typically between 175 and 346. There has been no correlation between the use of plant growth hormones and wound healing in human cell studies. A need exists for a plant derived cell migration agent that can be used to improve the
healing of animal tissue. Such a cell migration agent should be useful for human application with particular benefits in healing skin. Skin damage can include aging from sun or chemical exposure. Therefore, a suitable cell migration agent should be useful in minimizing or healing skin damage associated with aging and sun or chemical exposure.
SUMMARY OF THE INVENTION
A study involving human cells and plant growth enhancing agents has shown that Indole- 3-Acetic acid (also known as "Auxin") and its derivatives significantly increases the migration of fibroblast cells at five days after treatment initiation. Derivatives such as Indole-3-Acetyl-L- Phenylalanine have shown improved cell migration results. Likewise, derivatives such as Indole-
3-Acetic Acid Methyl Ester, Indole-3-Acetyl-L-Alanine, Indole-3-Acetyl-L-Aspartic Acid, and Indole-3-Acetylglycine should produce similar beneficial results.
Auxin and its derivative Indole-3-Acetyl-L-Phenylalanine maintained increased migration rates throughout the study. When administered in a dosage of at least 0.1 ppm, these compounds appear to have the ability to move healthy human fibroblast cells into areas void of cells more rapidly than if the agent were not present. Dosage levels of between 2 and 250 ppm showed better results. Once migrated, the healthy cells can then divide at their normal rate thus effectively filling the voided area quicker. This results in the plumping of the skin or healing of
wounds. The compounds can be delivered by topical or internal methods of application.
BRIEF DESCRIPTION OF THE DRAWINGS
For a more complete understanding of the present invention, and for further details and
advantages thereof, reference is now made to the following Detailed Description taken in conjunction with the accompanying drawings, in which:
Figure 1 is a bar chart showing the observed relative cell migration distances under the effect of three compounds under test for three days;
Figure 2 is a bar chart showing the observed relative cell migration distances under the effect of three compounds under test for five days;
Figure 3 is a bar chart showing the observed relative cell migration distances under the effect of three compounds under test for ten days;
Figure 4 is a bar chart showing the observed relative cell migration distances under the effect of three compounds under test for fourteen days; and
Figure 5 is a bar chart showing the migration response of Agent B versus fibroblast growth factor.
DETAILED DISCUSSION OF THE DRAWINGS
Improved wound healing has been observed with the use of Indole-3-Acetyl-L- Phenylalanine and Indole-3-Acetic acid. To verify these observations a study was conducted. The initial intent of these studies was to determine the possible cell growth promoting (mitogenic) activity of three plant-derived agents reported to promote wound healing in a small pilot study. The agents, blindly labeled A, B, and C; were tested at various concentrations to see if any had any mitogenic activity. Concentrations of 0.1, 1, 10, 25, 50, 100, and 250 ppm were tested. Agent A was a compound containing Indole-3-Acetic acid. Agent B was a compound containing Indole-3-Acetyl L-Phenylanine. Agent C was a compound containing gibberellic acid. Agent A was significantly inhibitory and agent B was mildly inhibitory of fibroblast cell growth. Fibroblasts are the chief cell of interest for these studies due to their central role in wound healing. Agent C had no significant influence on cell growth. The agents could be administered by injection, topical application, ingestion or inhalation.
These findings led to the postulation that the agents were instead promoting cell migration into the wound area, rather than cell growth. This hypothesis is based upon the fact that the initial phase of either cutaneous or vascular wound healing is cell migration into the wounded area rather than cell division to replace the lost or injured cells. To test this possibility that any one or more of these agents might contribute to wound healing by stimulating cell
migration, an in vitro wound model was developed. Skin fibroblasts were initially seeded in 60 mm diameter round culture dishes and allowed to grow until they covered the plate bottom in the presence of their normal growth medium. Upon attaining this confluence, a small circular area of cells of approximately 25 mm diameter was removed by scraping from the center of each plate. At this point the remaining cells were fed with a nutrient culture medium devoid of any added growth factors (which can act to stimulate cell migration). To this medium was added either a small amount of ethanol (used as a vehicle for drug administration) alone (control) or containing 250 ppm of either A,B, or C. Cells were refed with the respective medium every three days to maintain relatively constant drug levels within the media. The exact edge of the wound area was demarcated in black and migration distance was measured as the distance from that perimeter to the farthest cell inside the wound area using an inverted phase light microscope. Five measurements were taken around the perimeter of each wound area on days 3, 5, 10, and 14. Distances of fibroblast migration in response to agents A,B, and C were compared as presented in Figures 1, 2, 3 and 4. Most averages presented represent an average of 25 replicates (n=25).
Treatment groups were statistically compared using Student's unpaired / - analysis. The results as represented in Figures 1 to 4 indicate that agent B consistently and significantly increased fibroblast cell migration relative to cells treated with control media alone starting at day 5 after treatment initiation. Cells treated with agent A also showed a small but significant increase in cell migration relative to control cells at days 5 and 14.
The consistency and level of response to agent B stimulated the question as to its relative potency compared to an agent known to maximally stimulate fibroblast migration. Therefore, a comparison was made between fibroblast growth factor (FGF) and Agent B. FGF was used based on its well documented ability to stimulate fibroblast cell migration. Figure 5 illustrates that Agent B again increased cell migration but not as strongly as FGF (20 ng/ml). Specifically, the average migration at 7 days for B-treated cells was 4.1 ± 0.37 mm compared to 5.3 ± 0.24 mm for control cells. Comparatively, this data indicates that Agent B elicited about one-third the migratory response that was observed in response to FGF.
In conclusion, none of these agents are mitogenic and two are actually inhibitory of cell mitogenics (or cell growth). On the other hand, agents A and B had significant effects to stimulate fibroblast cell migration. The fact that these agents are not mitogenic may be a positive characteristic in terms of an agent that might be therapeutically applied. Thus, a mitogenic agent might provoke concerns relative to its potential effects as a carcinogen. The stimulation of migration by agents A and B raise the possibility that it may be an effective agent in promoting wound healing. Thus, Agents A and B should reduce the signs of skin aging. Although preferred embodiments of the present invention have been described in the
foregoing Detailed Description and illustrated in the accompanying Figures, it will be understood that the invention is not limited to the compounds disclosed, but is capable of
numerous variations in composition without departing from the spirit of the invention.
Accordingly, the present invention is intended to encompass such variations as fall within the
scope of the claims.

Claims

WE CLAIM:
1. A cell migration agent comprising a therapeutically effective dosage of Indole-3-Acetic Acid and its derivatives.
2. The cell migration agent of Claim 1 wherein said derivative comprises Indole-3-Acetyl-L- Phenylalanine.
3. The cell migration agent of Claim 1 wherein said derivative comprises Indole-3- Acetylglycine.
4. The cell migration agent of Claim 1 wherein said derivative comprises Indole-3-Acetyl- L-Aspartic Acid.
5. The cell migration agent of Claim 1 wherein said derivative comprises Indole-3-Acetyl-L- Alanine.
6. The cell migration agent of Claim 1 wherein said derivative comprises Indole-3-Acetic Acid Methyl Ester.
7. The cell migration agent of Claim 1 wherein said dosage comprises between 0.1 and 1000 ppm of the Indole-3 -Acetic Acid or its derivatives.
8. The cell migration agent of Claim 1 wherein said dosage comprises between 0.10 and 250 ppm of the Indole-3-Acetic Acid or its derivatives.
9. The cell migration agent of Claim 1 further comprises a chemical peel agent.
10. A method of promoting the healing of a tissue wound comprising delivering a therapeutically effective dosage of Indole-3-Acetic Acid or its derivatives to the tissue.
1 1. The method of Claim 10 wherein said step of delivering comprises topical application of the dosage.
12. The method of Claim 10 wherein said step of delivering comprises injection of the dosage.
13. The method of Claim 10 wherein said step of delivering comprises ingestion of the dosage.
14. The method of Claim 10 wherein said step of delivering comprises inhalation of the dosage.
15. The method of Claim 10 wherein said step of promoting further comprises treating aging skin.
PCT/US1998/013675 1997-06-30 1998-06-30 Skin aging and wound treatment using cell migration agents WO1999000079A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP50590299A JP2002504933A (en) 1997-06-30 1998-06-30 Cell transfer agent used for treatment of skin aging and wounds
EP98934222A EP1009345A4 (en) 1997-06-30 1998-06-30 Skin aging and wound treatment using cell migration agents
AU83797/98A AU8379798A (en) 1997-06-30 1998-06-30 Skin aging and wound treatment using cell migration agents
US09/273,681 US6174541B1 (en) 1998-06-30 1999-03-22 Skin aging and wound treatment using cell migration agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US88477997A 1997-06-30 1997-06-30
US08/884,779 1997-06-30

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/273,681 Continuation US6174541B1 (en) 1998-06-30 1999-03-22 Skin aging and wound treatment using cell migration agents

Publications (1)

Publication Number Publication Date
WO1999000079A1 true WO1999000079A1 (en) 1999-01-07

Family

ID=25385375

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/013675 WO1999000079A1 (en) 1997-06-30 1998-06-30 Skin aging and wound treatment using cell migration agents

Country Status (4)

Country Link
EP (1) EP1009345A4 (en)
JP (1) JP2002504933A (en)
AU (1) AU8379798A (en)
WO (1) WO1999000079A1 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008050198A3 (en) * 2006-10-23 2008-06-19 Clelia Barini Cosmetic method for toning up the dermis
FR2929115A1 (en) * 2008-03-31 2009-10-02 Exsymol Sa COSMETIC USE OF CONJUGATED COMPOUNDS OF INDOLIC AUXINS.
WO2013087834A3 (en) * 2011-12-16 2013-10-24 Syntivia Cosmetic composition for stimulating the cellular anti-aging functions of the skin
WO2021254754A1 (en) * 2020-06-19 2021-12-23 Unilever Ip Holdings B.V. Use of indole compounds for treating signs of skin aging
WO2021254753A1 (en) * 2020-06-19 2021-12-23 Unilever Ip Holdings B.V. Use of indole compounds for treating signs of skin aging

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4847283A (en) * 1983-01-10 1989-07-11 Harendza Harinxma Alfred J Ointment and method for treating skin lesions due to herpes virus

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1269573A (en) * 1959-06-09 1961-08-18 Auxins-based beauty products
US3271394A (en) * 1964-12-31 1966-09-06 Merck & Co Inc Alpha-indolyl-3-acetic acid esters
FR2597339A1 (en) * 1986-04-16 1987-10-23 Bounan Michel Three substances having antitumour activity, prepared by successive dilutions of plant growth hormones

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4847283A (en) * 1983-01-10 1989-07-11 Harendza Harinxma Alfred J Ointment and method for treating skin lesions due to herpes virus

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1009345A4 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008050198A3 (en) * 2006-10-23 2008-06-19 Clelia Barini Cosmetic method for toning up the dermis
FR2929115A1 (en) * 2008-03-31 2009-10-02 Exsymol Sa COSMETIC USE OF CONJUGATED COMPOUNDS OF INDOLIC AUXINS.
EP2116222A1 (en) * 2008-03-31 2009-11-11 Exsymol S.A.M. Cosmetic use of compounds combined with indolic auxins
WO2013087834A3 (en) * 2011-12-16 2013-10-24 Syntivia Cosmetic composition for stimulating the cellular anti-aging functions of the skin
WO2021254754A1 (en) * 2020-06-19 2021-12-23 Unilever Ip Holdings B.V. Use of indole compounds for treating signs of skin aging
WO2021254753A1 (en) * 2020-06-19 2021-12-23 Unilever Ip Holdings B.V. Use of indole compounds for treating signs of skin aging

Also Published As

Publication number Publication date
JP2002504933A (en) 2002-02-12
EP1009345A4 (en) 2002-03-13
EP1009345A1 (en) 2000-06-21
AU8379798A (en) 1999-01-19

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