EP1009345A1 - Traitement du vieillissement et des lesions de la peau a l'aide d'agents de migration cellulaire - Google Patents

Traitement du vieillissement et des lesions de la peau a l'aide d'agents de migration cellulaire

Info

Publication number
EP1009345A1
EP1009345A1 EP98934222A EP98934222A EP1009345A1 EP 1009345 A1 EP1009345 A1 EP 1009345A1 EP 98934222 A EP98934222 A EP 98934222A EP 98934222 A EP98934222 A EP 98934222A EP 1009345 A1 EP1009345 A1 EP 1009345A1
Authority
EP
European Patent Office
Prior art keywords
cell migration
indole
agent
dosage
migration agent
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.)
Withdrawn
Application number
EP98934222A
Other languages
German (de)
English (en)
Other versions
EP1009345A4 (fr
Inventor
Jin Song
John Koch
Marilyn Squier
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.)
NATERRA INTERNATIONAL, INC.
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
Publication of EP1009345A1 publication Critical patent/EP1009345A1/fr
Publication of EP1009345A4 publication Critical patent/EP1009345A4/fr
Withdrawn legal-status Critical Current

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

Abstract

Un agent de migration cellulaire favorise la cicatrisation de lésions en stimulant le mouvement de cellules fibroblastiques à l'opposé de la périphérie de la lésion. Les agents peuvent comprendre de l'acide indole-3-acétique et ses dérivés tels que indole-3-acétyle-L-phénylalanine. On a observé des augmentations significatives de la migration des cellules fibroblastiques à 5 jours après le début du traitement. Lorsqu'on les administre en un dosage compris entre 0,1 et 250 ppm, ces composés s'avèrent présenter la capacité de mouvoir les cellules fibroblastiques humaines dans des zones dépourvues de cellules plus rapidement que si l'agent était absent. Le résultat se traduit par l'arrondissement de la peau ou la cicatrisation de lésions. Les composés peuvent être administrés par des méthodes d'application locale ou interne.
EP98934222A 1997-06-30 1998-06-30 Traitement du vieillissement et des lesions de la peau a l'aide d'agents de migration cellulaire Withdrawn EP1009345A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US88477997A 1997-06-30 1997-06-30
US884779 1997-06-30
PCT/US1998/013675 WO1999000079A1 (fr) 1997-06-30 1998-06-30 Traitement du vieillissement et des lesions de la peau a l'aide d'agents de migration cellulaire

Publications (2)

Publication Number Publication Date
EP1009345A1 true EP1009345A1 (fr) 2000-06-21
EP1009345A4 EP1009345A4 (fr) 2002-03-13

Family

ID=25385375

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98934222A Withdrawn EP1009345A4 (fr) 1997-06-30 1998-06-30 Traitement du vieillissement et des lesions de la peau a l'aide d'agents de migration cellulaire

Country Status (4)

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

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMO20060339A1 (it) * 2006-10-23 2008-04-24 Clelia Barini Metodo cosmetico di tonificazione del derma
FR2929115B1 (fr) * 2008-03-31 2010-06-04 Exsymol Sa Utilisation cosmetique de composes conjugues d'auxines indoliques.
FR2984122B1 (fr) * 2011-12-16 2014-08-01 Syntivia Composition cosmetique pour stimuler les fonctions cellulaires anti-vieillissement de la peau
WO2021254753A1 (fr) * 2020-06-19 2021-12-23 Unilever Ip Holdings B.V. Utilisation de composés d'indole pour traiter les signes du vieillissement de la peau
WO2021254754A1 (fr) * 2020-06-19 2021-12-23 Unilever Ip Holdings B.V. Utilisation de composés indoliques pour traiter les signes du vieillissement de la peau

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1269573A (fr) * 1959-06-09 1961-08-18 Produits de beauté à base d'auxines
US3271394A (en) * 1964-12-31 1966-09-06 Merck & Co Inc Alpha-indolyl-3-acetic acid esters
FR2597339A1 (fr) * 1986-04-16 1987-10-23 Bounan Michel Trois substances a activite antitumorale preparees par dilutions successives d'hormones vegetales de croissance.

Family Cites Families (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

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1269573A (fr) * 1959-06-09 1961-08-18 Produits de beauté à base d'auxines
US3271394A (en) * 1964-12-31 1966-09-06 Merck & Co Inc Alpha-indolyl-3-acetic acid esters
FR2597339A1 (fr) * 1986-04-16 1987-10-23 Bounan Michel Trois substances a activite antitumorale preparees par dilutions successives d'hormones vegetales de croissance.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO9900079A1 *

Also Published As

Publication number Publication date
EP1009345A4 (fr) 2002-03-13
AU8379798A (en) 1999-01-19
WO1999000079A1 (fr) 1999-01-07
JP2002504933A (ja) 2002-02-12

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