FR2769225A1 - Topical compositions containing hypophysis extract for the repair or regeneration of melanocytes - Google Patents

Topical compositions containing hypophysis extract for the repair or regeneration of melanocytes Download PDF

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FR2769225A1
FR2769225A1 FR9712342A FR9712342A FR2769225A1 FR 2769225 A1 FR2769225 A1 FR 2769225A1 FR 9712342 A FR9712342 A FR 9712342A FR 9712342 A FR9712342 A FR 9712342A FR 2769225 A1 FR2769225 A1 FR 2769225A1
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compositions according
melanocytes
extract
excipient
regeneration
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FR2769225B1 (en
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Yvon Gauthier
Marie Helene Podesta
Le Moult Christine Tassi
Carole Trassard
Pierre Viornery
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/55—Glands not provided for in groups A61K35/22 - A61K35/545, e.g. thyroids, parathyroids or pineal glands
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • 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
    • A61Q19/04—Preparations for care of the skin for chemically tanning the skin

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Developmental Biology & Embryology (AREA)
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  • Engineering & Computer Science (AREA)
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  • Epidemiology (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Virology (AREA)
  • Dermatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Endocrinology (AREA)
  • Birds (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Use of hypophysis extracts in compositions for promoting pigmentation. Topical composition for the repair or regeneration of melanocytes comprises hypophysis extracts and a carrier.

Description

NOUVELLES COMPOSITIONS FAVORISANT LA PIGMENTATION
ET LEUR EMPLOI EN DERMOCOSMETOLOGIE
La présente invention concerne le domaine de la chimie organique et plus particulièrement celui de la chimie thérapeutique.NEW PIGMENTATION-PROMOTING COMPOSITIONS
AND THEIR USE IN DERMOCOSMETOLOGY
The present invention relates to the field of organic chemistry and more particularly that of therapeutic chemistry.

Elle a plus particulièrement pour objet des compositions pharmaceutiques visant à la réparation ou à la régénération des mélanocytes de manière à assurer une repigmentation naturelle des téguments.It relates more particularly to pharmaceutical compositions aimed at repairing or regenerating melanocytes so as to ensure natural repigmentation of the integuments.

La présente invention a spécifiquement pour objet des compositions destinées à l'application topique pour la régénération ou la réparation des mélanocytes caractérisées en ce qu'elles renferment, à titre de principe actif, un extrait d'hypophyse additionné éventuellement de facteurs de croissance ettou de sels minéraux et/ou d'acides aminés et/ou de vitamines ou de facteurs vitaminiques, dans un excipient ou un véhicule approprié pour la voie d'administration.The present invention specifically relates to compositions intended for topical application for the regeneration or repair of melanocytes, characterized in that they contain, as active principle, an extract of pituitary gland optionally added with growth factors and / or mineral salts and / or amino acids and / or vitamins or vitamin factors, in an excipient or a vehicle suitable for the route of administration.

On sait déjà que les extraits de lobe postérieur d'hypophyse jouent un rôle dans la pigmentation cutanée induite par les rayonnements ultraviolets. Cet effet résulte d'une augmentation de la sécrétion d'a-mélanotropine, en particulier chez la souris.We already know that posterior pituitary lobe extracts play a role in skin pigmentation induced by ultraviolet radiation. This effect results from an increase in the secretion of α-melanotropin, in particular in mice.

On sait aussi que les extraits de lobe intermédiaire d'hypophyse jouent un rôle sur les taux d'ARNm et de pro-opiomélanocortine chez le crapaud Xenopus laevis par adaptation à l'arrière plan coloré.We also know that extracts from the pituitary intermediate lobe play a role in the levels of mRNA and pro-opiomelanocortin in the toad Xenopus laevis by adaptation to the colored background.

Des essais ont montré également les effets d'une administration d'une hormone hypophysaire (melanin concentrating hormone) sur la pigmentation de la truite arcen-ciel par augmentation du taux de a-MSH sous l'effet du stress.Tests have also shown the effects of the administration of a pituitary hormone (melanin concentrating hormone) on the pigmentation of rainbow trout by increasing the level of a-MSH under the effect of stress.

De même, on a montré chez la truite arc-en-ciel les effets de l'hypophysectomie sur la pigmentation et sur la croissance. Similarly, the effects of hypophysectomy on pigmentation and growth have been shown in rainbow trout.

On sait également que l'hypothalamus joue un rôle dans les réactions de pigmentation mélanophoriques et sur la régulation des taux de mélanocyte stimulating hormone.It is also known that the hypothalamus plays a role in melanophoric pigmentation reactions and in the regulation of melanocyte stimulating hormone levels.

Toutes ces études ont été menées sur des batraciens ou des rongeurs qui ont des cellules très sensibles aux variations de lumière.All these studies were carried out on amphibians or rodents which have cells very sensitive to variations in light.

On sait également qu'on peut cultiver des cellules animales et notamment des cellules de mélanomes de glande pituitaire pour obtenir des corticotropines et des hormones de croissance. On peut ainsi mettre en culture des mélanocytes humains ou animaux.It is also known that animal cells and in particular cells of melanoma of the pituitary gland can be cultivated to obtain corticotropins and growth hormones. It is thus possible to culture human or animal melanocytes.

L'objet de l'invention est plus précisément de réaliser le développement des mélanocytes par application cutanée d'extrait hypophysaire pour combler un déficit en mélanocytes cutanés ou une détérioration des mélanocytes.The object of the invention is more precisely to carry out the development of melanocytes by skin application of pituitary extract to fill a deficit in skin melanocytes or a deterioration of the melanocytes.

On sait en effet, que les mélanocytes sont contenus dans des tissus très fragiles et qu'une simple friction ou une plaie ou une brûlure est susceptible de provoquer la détérioration des mélanocytes. Cette détérioration peut même devenir pathologique dans les cas de vitiligo qui entrainent une dépigmentation de zones cutanées plus ou moins étendues.We know, in fact, that melanocytes are contained in very fragile tissues and that a simple friction or a wound or a burn is likely to cause the deterioration of melanocytes. This deterioration can even become pathological in cases of vitiligo which lead to a depigmentation of more or less extensive skin areas.

II existe, de ce fait, un besoin en moyens thérapeutiques pour traiter les défauts de pigmentation cutanée en évitant d'avoir recours à des greffes de peau pour le traitement de zones dépigmentées étendues. There is therefore a need for therapeutic means to treat skin pigmentation defects while avoiding the need for skin grafts for the treatment of large depigmented areas.

Les compositions selon l'invention renferment comme principe actif l'extrait hypophysaire total ou un extrait de lobe antérieur ou un extrait de lobe postérieur en sachant que c'est l'extrait hypophysaire total qui est le plus actif.The compositions according to the invention contain as active principle the total pituitary extract or an anterior lobe extract or an posterior lobe extract knowing that it is the total pituitary extract which is the most active.

L'extrait hypophysaire peut être additionné de facteurs de croissance qui renforcent son action comme par exemple, I'endotheline, le facteur de croissance bFGF2 ou le facteur SCF. On peut ajouter un de ces facteurs de croissance ou plusieurs facteurs de croissance à l'extrait hypophysaire.The pituitary extract can be supplemented with growth factors which enhance its action such as, for example, the endotheline, the growth factor bFGF2 or the factor SCF. One or more of these growth factors can be added to the pituitary extract.

Les compositions selon l'invention contiennent, en outre, des sels minéraux et/ou des facteurs biologiques qui contribuent à la réparation des mélanocytes et à leur développement.The compositions according to the invention additionally contain mineral salts and / or biological factors which contribute to the repair of melanocytes and to their development.

L'extrait hypophysaire est celui qui figure à la pharmacopée française sous le nom de poudre d'hypophyse totale. La poudre d'hypophyse est définie comme provenant de la dessiccation et de la pulvérisation de glandes hypophysaires entières prélevées sur des bovins, des chevaux, des moutons, des porcins, après les avoir débarrassés de toutes les portions périglandulaires qui ont pu les accompagner lors du prélèvement ou de l'extirpation sur l'animal.The pituitary extract is that which appears in the French pharmacopoeia under the name of total pituitary powder. Pituitary powder is defined as coming from the desiccation and spraying of whole pituitary glands taken from cattle, horses, sheep, pigs, after having rid them of all the periglandular portions which may have accompanied them during the removal or extirpation from the animal.

La poudre de lobe antérieur est préparée par dessiccation et pulvérisation du lobe antérieur de l'hypophyse de bovins ou de cheval. Ce lobe doit être soigneusement séparé du lobe postérieur lors de la dissection.The anterior lobe powder is prepared by drying and spraying the anterior lobe of the pituitary gland of cattle or horses. This lobe should be carefully separated from the posterior lobe during dissection.

Les compositions selon l'invention sont formulées en vue de l'application topique sous forme de préparations solides comme des pommades, des savons ou des poudres, ou sous forme semi-fluide comme des gels, des crèmes, ou sous forme fluide comme des laits, des lotions ou des émulsions.The compositions according to the invention are formulated for topical application in the form of solid preparations such as ointments, soaps or powders, or in semi-fluid form such as gels, creams, or in fluid form such as milks , lotions or emulsions.

A cette fin, les ingrédients actifs seront incorporés par simple mélange ou par mise en dispersion ou émulsion dans une base lipophile ou dans un excipient gélifié ou réparti dans une émulsion O/W ou W/O selon les possibilités.To this end, the active ingredients will be incorporated by simple mixing or by dispersion or emulsion in a lipophilic base or in a gelled excipient or distributed in an O / W or W / O emulsion according to the possibilities.

Parmi les excipients lipophiles, on pourra citer l'alcool cetostéarylique, L'acide palmitostéarique, les oxyesters de glycérol d'huiles végétales, le perhydrosqualiène, la paraffine liquide, les huiles de silicone, I'huile d'avocat, I'huile de germe de blé ou l'huile de Jojob
Parmi les excipients gélifiés, on pourra citer les polymères d'acide acrylique et/ou d'acide méthacrylique connus sous le nom de Carbomères, les polyacrylamides, le complexe glycéro-vaseline, I'oléate de lysine, le dioxyde de titane solubilisé et des silices, les bases tensioactives amphotères ou la gomme xanthanne, les laits gélifiés à l'huile d'amande douce.Among the lipophilic excipients, mention may be made of cetostearyl alcohol, palmitostearic acid, glycerol oxyesters of vegetable oils, perhydrosqualiene, liquid paraffin, silicone oils, avocado oil, olive oil. wheat germ or Jojob oil
Among the gelled excipients, mention may be made of polymers of acrylic acid and / or methacrylic acid known under the name of Carbomers, polyacrylamides, glycerol-vaseline complex, lysine oleate, solubilized titanium dioxide and silica, amphoteric surfactant bases or xanthan gum, milk gelled with sweet almond oil.

Parmi les véhicules liquides, on pourra citer les polyoxyéthylène glycols 1500 ou 4000, les polyglycérols, le propylène glycol, I'huile d'onagre émulsionnée, et notamment les produits vendus sous la dénomination Neribase (Néribase crème,
Néribase pommade et Neribase gras).Among the liquid vehicles, mention may be made of polyoxyethylene glycols 1500 or 4000, polyglycerols, propylene glycol, emulsified evening primrose oil, and in particular the products sold under the name Neribase (cream neribase,
Nerbase ointment and Neribase gras).

Parmi les sels minéraux que l'on peut incorporer dans les compositions de l'invention, on pourra citer les sels de calcium (chlorure de calcium), les sels de fer (sulfate ferreux), les sels de manganèse (sulfate de manganèse), les sels de nickel (chlorure de nickel), les sels d'étain (chlorure stanneux), les sels de zinc (sulfate de zinc).Among the mineral salts which can be incorporated into the compositions of the invention, mention may be made of calcium salts (calcium chloride), iron salts (ferrous sulfate), manganese salts (manganese sulfate), nickel salts (nickel chloride), tin salts (stannous chloride), zinc salts (zinc sulfate).

On pourra également incorporer des facteurs vitaminiques comme l'acide folique, le folinate de calcium, le Niacinamide, L'acide pantothénique, la pyridoxine, la riboflavine, la Thiamine, I'hydroxocobalamine, L'acide thiooctique, la biotine, L'acide pangamique, la choline, le myo-inositol, la thymidine ou l'adénine.We can also incorporate vitamin factors such as folic acid, calcium folinate, Niacinamide, Pantothenic acid, pyridoxine, riboflavin, Thiamine, hydroxocobalamin, Thiooctic acid, biotin, Acid pangamic, choline, myo-inositol, thymidine or adenine.

On pourra également incorporer des aminoacides, naturels ou synthétiques, racémiques ou optiquement actifs comme la L-alanine, la L-arginine, la Lasparagine, L'acide L-aspartique, la L-cystéine, la L-cystine, L'acide L-glutamique, la
L-glutamine, la glycine, la L-lysine, la L-méthionine, la L-phenylalanine, la L-proline, la N-acétylproline, I'hydroxyproline, la L-sérine, la L-tyrosine, la L-thréonine, le Ltryptoph ane, la L-valine, la putrescine, la cadavérine ou l'homarine.We can also incorporate amino acids, natural or synthetic, racemic or optically active such as L-alanine, L-arginine, Lasparagine, L-aspartic acid, L-cysteine, L-cystine, L acid -glutamic, the
L-glutamine, glycine, L-lysine, L-methionine, L-phenylalanine, L-proline, N-acetylproline, hydroxyproline, L-serine, L-tyrosine, L-threonine , Ltryptoph ane, L-valine, putrescine, cadaverine or homarine.

Les compositions selon l'invention peuvent, en outre, contenir des corticostéroïdes comme l'hydrocortisone ou des protéines comme l'autolysat de levure de bière, le sérum de cheval ou le sérum de veau fétal. The compositions according to the invention may, in addition, contain corticosteroids such as hydrocortisone or proteins such as brewer's yeast autolysate, horse serum or fetal calf serum.

L'extrait hypophysaire est contenu dans les compositions de l'invention à des doses qui s'échelonnent de 1 à 100 mg pour 100 g. Une dose préférée est celle qui contient de 1 à 200 pg d'extrait hypophysaire par ml et tout particulièrement de 100 à 200 ,ug/ml. The pituitary extract is contained in the compositions of the invention in doses which range from 1 to 100 mg per 100 g. A preferred dose is that which contains from 1 to 200 μg of pituitary extract per ml and more particularly from 100 to 200 μg / ml.

Les compositions selon l'invention sont appliquées de une à quatre fois par jour en massages légers sur la zone dépigmentée. Le résultat thérapeutique désiré est atteint au bout de 20 à 40 jours. II convient tout particulièrement pour le traitement de zones dépigmentées liées à des cicatrices post-thérapeutiques, des cicatrices achromiques, de l'achromisme secondaire ou du vitiligo.The compositions according to the invention are applied from one to four times a day in light massages on the depigmented area. The desired therapeutic result is achieved after 20 to 40 days. It is particularly suitable for the treatment of depigmented areas linked to post-therapeutic scars, achromic scars, secondary achromism or vitiligo.

Les exemples suivants illustrent l'invention sans toutefois la limiter.The following examples illustrate the invention without, however, limiting it.

FORTES GALENIQUES ENVISAGEES: 1) Gel transparent ou opalescent thixotrope
Formule à partir de polymères synthétiques ou naturels, contenant des corps gras
hydro-solubles, permettant une application aisée et une pénétration immédiate.STRONG GALENICS CONSIDERED: 1) Transparent or opalescent thixotropic gel
Formula from synthetic or natural polymers, containing fatty substances
water-soluble, allowing easy application and immediate penetration.

2) Crème HIE (phase continue aqueuse)
incorporant ou non une formule retard (micro-réservoirs à parois en matériaux
synthétiques ou naturels), excipient non ionique à pH contrôlé 3) Lotion hydro-glyco-alcoolique sous forme d'aérosol (sous gaz inerte) 2) HIE cream (aqueous continuous phase)
incorporating or not a delay formula (micro-tanks with material walls
synthetic or natural), non-ionic excipient at controlled pH 3) Hydro-glycosalcoholic lotion in aerosol form (under inert gas)

Claims (10)

pour cette voie d'administration. for this route of administration. principe actif un extrait d'hypophyse dans un excipient ou un véhicule approprié active ingredient pituitary extract in a suitable excipient or vehicle réparation des mélanocytes caractérisées en ce qu'elles renferment à titre de repair of melanocytes characterized in that they contain as REVENDICATIONS 1. Compositions destinées à l'application topique pour la régénération ou la CLAIMS 1. Compositions for topical application for regeneration or 2. Compositions selon la revendication 1, dans lesquelles le principe est additionné2. Compositions according to claim 1, in which the principle is added de facteurs de croissance. growth factors. 3. Compositions selon la revendication 1, dans lesquelles le principe actif est3. Compositions according to claim 1, in which the active principle is additionné de sels minéraux. added with mineral salts. 4. Compositions selon la revendication 1, dans lesquelles le principe actif est4. Compositions according to claim 1, in which the active principle is additionné d'acides aminés naturels ou synthétiques. with added natural or synthetic amino acids. 5. Compositions selon la revendication 1, dans lesquelles le principe actif est5. Compositions according to claim 1, in which the active principle is additionné de facteurs vitaminiques. supplemented with vitamin factors. 6. Compositions selon l'une des revendications précédentes, dans lesquelles le6. Compositions according to one of the preceding claims, in which the facteur de croissance est choisi parmi l'endothéline, le facteur de croissance growth factor is chosen from endothelin, the growth factor bFGF2 et le facteur SCF. bFGF2 and the factor SCF. 7. Compositions selon l'une des revendications précédentes, dans lesquelles7. Compositions according to one of the preceding claims, in which l'extrait d'hypophyse est présent à des doses s'échelonnant de 1 à 100 mg pour pituitary extract is present in doses ranging from 1 to 100 mg for 100 g de préparation. 100 g of preparation. 8. Compositions selon la revendication 7, dans lesquelles l'extrait d'hypophyse est8. Compositions according to claim 7, in which the pituitary extract is présent de préférence à des doses s'échelonnant de 1 à 200 pg d'extrait par ml  preferably present at doses ranging from 1 to 200 pg of extract per ml de préparation. of preparation. 9. Compositions selon l'une des revendications précédentes, dans lesquelles9. Compositions according to one of the preceding claims, in which l'excipient est un excipient solide ou semi-visqueux the excipient is a solid or semi-viscous excipient 10. Compositions selon l'une des revendications précédentes, dans lesquelles10. Compositions according to one of the preceding claims, in which l'excipient est un véhicule fluide ou pulvérulent.  the excipient is a fluid or powdery vehicle.
FR9712342A 1997-10-03 1997-10-03 NEW COMPOSITIONS TO PROMOTE PIGMENTATION AND THEIR USE IN DERMO-COSMETOLOGY Expired - Fee Related FR2769225B1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1222913A1 (en) * 1999-10-21 2002-07-17 Kao Corporation Depilatories and agents for external use

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5204325A (en) * 1988-12-15 1993-04-20 Lindstrom Richard L Viscoelastic solution
JPH0648925A (en) * 1992-07-30 1994-02-22 Lion Corp Grey hair preventive

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5204325A (en) * 1988-12-15 1993-04-20 Lindstrom Richard L Viscoelastic solution
JPH0648925A (en) * 1992-07-30 1994-02-22 Lion Corp Grey hair preventive

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PATENT ABSTRACTS OF JAPAN vol. 018, no. 282 (C - 1205) 30 May 1994 (1994-05-30) *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1222913A1 (en) * 1999-10-21 2002-07-17 Kao Corporation Depilatories and agents for external use
EP1222913A4 (en) * 1999-10-21 2003-06-25 Kao Corp Depilatories and agents for external use
US6884772B1 (en) 1999-10-21 2005-04-26 Kao Corporation Depilatories and agents for external use

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