CN1298290A - Use of retinoic acid activity inhibitors to slow down hair loss - Google Patents
Use of retinoic acid activity inhibitors to slow down hair loss Download PDFInfo
- Publication number
- CN1298290A CN1298290A CN99804411A CN99804411A CN1298290A CN 1298290 A CN1298290 A CN 1298290A CN 99804411 A CN99804411 A CN 99804411A CN 99804411 A CN99804411 A CN 99804411A CN 1298290 A CN1298290 A CN 1298290A
- Authority
- CN
- China
- Prior art keywords
- benzoic acid
- tretinoin
- activity inhibitor
- slow down
- tetramethyl
- 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.)
- Pending
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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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
- A61Q7/02—Preparations for inhibiting or slowing hair growth
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/382—Heterocyclic compounds having sulfur as a ring hetero atom having six-membered rings, e.g. thioxanthenes
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/603—Salicylic acid; Derivatives thereof having further aromatic rings, e.g. diflunisal
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- A—HUMAN NECESSITIES
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- 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
- A61K8/67—Vitamins
- A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
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- 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
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention concerns the use in or for preparing a cosmetic or pharmaceutical, preferably dermatological, composition, of at least a retinoic activity inhibitor, said composition being designed to slow down or preventing the growth of hairs and/or hair. Said composition is also designed to slow down loss of hairs and/or hair.
Description
The present invention relates at least a tretinoin activity inhibitor aspect the most generalized in cosmetic composition or be used for slowing down or preventing a kind of application of pharmaceutical composition of and/or multiple hair growth in preparation at it.Compositions of the present invention can also be slowed down coming off of a kind of and/or multiple hair.The present invention also relates to be used to improve the non-therapeutic processing method of hair growth.
In human body, the growth of hair and renewal thereof depend primarily on the activity of hair follicle.Hair follicle is active in periodically and in itself comprising three periods, just nascent phase, catagen and resting stage.
Active nascent phase or trophophase continue the several years, and hair is elongated in this process, are the catagen of an extremely short and transition behind nascent phase or the trophophase, and catagen continues several weeks, follows by resting stage, is also referred to as resting stage, lasting several moons in this period.
In the latter stage of resting stage, alopecia and begin new cycle period.Therefore, hair is fixing to be upgraded, and at any time, has 10% hair to be in resting stage in about 150000 hairs that constitute hair approximately and upgrades in the several months.
In most cases, coming off too early of hair can appear in the individuality of genetic predisposition is arranged, and this especially occurs among the male.This relates more specifically to short male or short male pattern baldness or other male levy alopecia.
The interruption that this alopecia is upgraded owing to hair in fact, the period frequency that it will at first cause the hair quality to consume is accelerated, and the cycle frequency that causes number of hairs to consume is subsequently accelerated.Degenerate by so-called " end " hair, hair was tapered in the later stage (downy stage).Some zone preferentially is affected, particularly male's temporo district and frontal region, and in the women, can observe the dispersivity alopecia of head.
People in cosmetics and the pharmacy industry have sought for many years can suppress or reduce the alopecia effect, particularly reduces alopecia or brings out or promote the material of natural on-off cycles of hair growth.
In this respect, multiple different active substance and chemical compound are disclosed.As prompting, especially noteworthy: vitamins, as vitamin E; Aminoacid is as serine or methionine; Vasodilation is as acetylcholine and derivant thereof; Estrogen, for example estradiol; Keratolytic is as salicylic acid; Or chemical compound, as 2,4-diaminourea-6-piperidines and pyrimidine 3-oxide or US4596812 disclosed " Minoxidil ", or its many derivants, for example be disclosed among patent application EP 353123, EP356271, EP408442, EP522964, EP420707, EP459890 and the EP519819 those.
Noteworthy 6-amino-1 in addition, 2-dihydro-1-hydroxyl-2-imino group-4-piperidines and pyrimidine and derivant thereof, they are disclosed among the patent US-A-4139619 in detail.
Except those known already materials, also have usually suitable and be of value to and obtain active material.
Although Minoxidil is a reference compound in affiliated field, this chemical compound has appreciable side effect, makes its application complicated thus.
Discovery can act on hair growth and/or alopecia but the material that do not have any harmful side effect remains a main target of scientific research.
In addition, can to slow down a kind of chemical compound of and/or multiple hair growth be very useful in searching.
It has been generally acknowledged that all-trans retinoic acid is by working aspect cell differentiation and/or the hypertrophy with the nuclear receptor or RAR (retinoic acid receptors) interaction that are contained in the nucleus.The composite structure analog (generally being called " retinoid (retinoid) ") of many all-trans retinoic acids or 9-cis-tretinoin is disclosed in the document.Have three kinds of rar receptor hypotypes that identified at present, they are respectively RAR-α, RAR-β and RAR-γ.And after part (the being all-trans retinoic acid) combination, these receptors interact in the level of specific effect element (RARE) and the promoter region of gene under the adjusting of tretinoin.
Some analog can be in conjunction with the rar receptor hypotype (α, β or γ) specific with activation.At last, other analog do not demonstrate the specific selectivity activity to these different receptors.In this respect, for example, all-trans retinoic acid is regardless of hypotype ground and activates RAR (the exciting part of RAR specificity).
Regulate the rar receptor activity by combining with rar receptor, tretinoin and retinoid generally are believed to treat various skin disease or disease and more specifically are alopecia.
On the contrary, the tretinoin antagonist suppresses the metabolite of active or its cellular level of tretinoin.This is particularly related to and can combines with rar receptor but do not cause observed active rar antagonist in tretinoin or retinoid.
So, show that now RAR α receptor antagonist can suppress the cell differentiation that the HL60 cell line cell brought out by retinoid, or on the contrary, reverse mice B-cell and suppress (people such as C.Apfel, " institute of American Academy of Sciences newspaper " 89 by the propagation that retinoid brings out, 1992,7129-7133).
Multiple tretinoin antagonist has been described in patent application EP0740937.Their recommended being used for the treatment of with rar receptor are excessively regulated and/or hypervitaminosis A diseases associated and/or disease, are generally inflammation, allergia and/or immunity disease, as psoriasis.Also disclose them simultaneously and can be used for treating alopecia.
Through behind the big quantity research, the applicant is very surprised and be surprised to find that, by suppressing in the hair follicle zone activity of tretinoin in the Skin Cell, can slow down the cycle period of hair basically, particularly slows down nascent phase or resting stage.
More specifically, have now found that,, can slow down and/or prevent coming off of the growth of one or more hairs and/or slow down a kind of and/or multiple hair by suppressing the activity of tretinoin.
Above-mentioned discovery has constituted basis of the present invention.
So, according to first aspect of the present invention, provide at least a tretinoin activity inhibitor or be used to prepare cosmetics or pharmaceutical composition, the application in the preferred skin composition, described compositions is the growth that is used to slow down and/or prevent a kind of and/or multiple hair.
In aspect second of the present invention, provide at least a tretinoin activity inhibitor or be used to prepare cosmetics or pharmaceutical composition, the application in the preferred skin composition, described compositions is used to slow down coming off of a kind of and/or multiple hair.
The tretinoin activity inhibitor can work according to two kinds of approach, and article one approach provides the cellular metabolism that quickens tretinoin, reduces its cell concentration thus, and the second approach is by its effect at cellular level of antagonism.
According to the present invention, the tretinoin activity inhibitor is the promoter of retinoic acid metabolism or antagonist, and it reverses excitement or part agonism to tretinoin.
According to the present invention, word " tretinoin antagonist " is meant the chemical compound of the effect that suppresses tretinoin and/or its metabolite and/or retinoid.More specifically, these chemical compounds are to combine with rar receptor but the rar antagonist of activated receptor not.
This is meant especially and suppresses the active chemical compound of tretinoin " in the body " that these chemical compounds are to screen according to the test of describing among the patent application EP96401170 (being filed in 1996.5.31, denomination of invention CIRD GALDERMA).This relates to a kind of method that is used to identify the rar antagonist molecule, it is characterized in that it may further comprise the steps: (ⅰ) with the RAR agonist molecule local coating of q.s in the zone of mammal skin, (ⅱ) step (1) before, during or afterwards, to have the molecule general of RAR-antagonistic activity or topical in the same area of same mammal or this mammal skin and (ⅲ) in this skin area of assessment mammal to the reaction of above-mentioned processing.So when the administration molecule was rar antagonist, not observing skin thickness in this mammal skin zone with the processing of RAR agonist molecule increased or has reduced.Observe inhibition thus to reaction.In the reality, mammal is rodent such as mice, rat, Cavia porcellus, hamster or rabbit.Selected mammalian skin zone can be any zone of mammalian organism.On the evaluated mammal skin zone to the reaction of this processing corresponding to the clinical pathological changes of skin in should the zone.Usually, this evaluated reaction is corresponding to the varied in thickness in the skin area of handling thus.So, can measure the thickness of the skin area after this processing by any known method.When selected skin area when being level and smooth, can measure its thickness by folding skin.In actual condition, adopt ear skin.In this case, ear's thickness can be measured with " oditest " micrometer.Need not, the assessment of step (ⅲ) is equivalent to the mensuration to the reaction of processed skin area, and and compares with the reaction of the same skin area of RAR agonist molecule processing separately under the same conditions.The suitable chemical compound that can cause mice embryonic teratoma (F9) cell differentiation that is selected from of RAR agonist molecule.The secretion of following the plasminogen activator of this differentiation generation is the F9 cell produces biological respinse to this compounds a indication.Know also that in addition it is relevant with the activity on rar receptor to the affinity of rar receptor with them that these chemical compounds bring out the ability of plasminogen activator, rar receptor for the F9 cell be endogenic (" dermatopharmacology " 1990,3,256-267).In the exciting molecule of the RAR that brings out the F9 cell differentiation, what can mention especially is:
-all-trans retinoic acid,
-2-(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl-2-naphthyl)-6-benzo [b] thiophenic acid,
-4-[(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl-2-naphthyl) formamido group] benzoic acid,
-4-[(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl-2-naphthyl) carbamoyl] benzoic acid.
The amount that the abundant amount of coated RAR-agonist molecule is equivalent to step (ⅰ) back can observe described reaction in the processed zone of mammal skin the time.So preferably this amount is 0.0001% to 2% weight of coated liquor capacity, and depend on the character of used RAR agonist molecule.
In context, word " local approach " is meant any by being applied directly to the technology of body surface (or outside) zone with the product administration, word " general approach " is meant through the technology of any way except local approach with the product administration, for example enteral and/or non-enteral administration.In the situation of general approach, preferably adopt oral administration.
Described tretinoin antagonist is meant especially and is disclosed among patent application EP661259, EP740937, EP658553, EP568898, WO95/33745, WO97/09297 and the WO94/14777, and be disclosed in some scientific and technical literatures, especially people (J.Med.Chem. such as Eyrolles, 37,1994,1508-1517; Med.Chem.Res., 2,1992,361-367) and people such as Kaneko (Med.Chem.Res., 1,1991, the 220-225) chemical compound in, these documents are hereby incorporated by; With the effect that suppresses tretinoin and/or retinoid.
Be applicable to that rar antagonist of the present invention specifically is selected from following compounds:
-4-[7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl] benzoic acid,
-4-[7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl] salicylic acid,
-6-[7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl] nicotinic acid,
-4-{[5,6-dihydro-5,5-dimethyl-8-(4-aminomethyl phenyl)-2-naphthyl] acetenyl } benzoic acid,
-(E)-and 4-[2-(4,4-dimethyl-7-Oxy-1 in heptan, 1-dioxo-3,4-dihydro-2H-1-benzo thiapyran-6-yl) acrylic] benzoic acid,
-4-[4,5,7,8,9,10-six hydrogen-7,7,10,10-tetramethyl-1-(3-pyridylmethyl) anthra [1,2-b] pyrroles-3-yl] benzoic acid,
-4-[4,5,7,8,9,10-six hydrogen-7,7,10,10-tetramethyl-1-(3-pyridylmethyl) sulfo-anthra [1,2-b] pyrroles-3-yl] benzoic acid,
-4-[4,5,7,8,9,10-six hydrogen-7,7,10,10-tetramethyl-1-(3-pyridylmethyl) anthra [1,2-d] pyrazole-3-yl] benzoic acid,
-4-[3-(two adamantyls)-4-methoxybenzoyl amino] benzoic acid,
-4-[3-(two adamantyls)-4-methoxybenzoyl oxygen base] benzoic acid,
-4-(N-phenyl-5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl naphtho-[2,3-d] imidazoles-2-yl) benzoic acid,
-4-(N-benzyl-5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl naphtho-[2,3-d] imidazoles-2-yl) benzoic acid,
-4-(5H-7,8,9,10-tetrahydrochysene-5,7,7,10,10-pentamethyl benzo [c] naphtho-[2,3-b] diaza -3-yl) benzoic acid,
-4-[1-(1-methoxyl group-2,2,2-trifluoroethyl)-5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl-3-anthryl] benzoic acid,
-4-(5,5-dimethyl-8-phenyl-5,6-dihydronaphthalene-2-ethyl-acetylene base) benzoic acid,
-4-(5,5-dimethyl-8-p-methylphenyl-5,6-dihydronaphthalene-2-ethyl-acetylene base) benzoic acid,
-4-[4-(biphenyl-2-yl) fourth-3-alkene-1-alkynyl] benzoic acid,
-(E)-4-[[3-oxo-3-[3-(1-adamantyl)-4-methoxy ethoxy-methoxyphenyl]-the 1-acrylic]] benzoic acid.
The useful rar antagonist of the present invention is preferably from following chemical compound:
-4-(5,5-dimethyl-8-p-methylphenyl-5,6-dihydronaphthalene-2-ethyl-acetylene base) benzoic acid,
-4-(7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl) benzoic acid,
-4-(7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl) salicylic acid,
-6-(7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl) nicotinic acid.
Be applicable to that rar antagonist of the present invention is more preferably from following compounds:
-4-[7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl] salicylic acid,
-6-[7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl] nicotinic acid.
Further feature of the present invention, aspect, purpose and advantage are being read hereinafter description and a plurality of concrete but will become clearer and more definite after the non-limiting examples, and described embodiment is only for illustrating the present invention.
Usually it should be noted that in the context of the present invention, obviously can use the mixture of inhibitor, certainly, condition is that these mixture have kept suitable beneficial effect.
The amount that can be used for inhibitor of the present invention obviously depends on expected effect.It also depends on inhibitor.So this consumption is to change in wide region.
As adopting the tretinoin activity inhibitor in the fruit cosmetic composition, in order to provide the order of magnitude, said composition can contain and accounts for said composition gross weight 0.0001% to 5% (weight), the preferably inhibitor of 0.01% of the said composition gross weight to 2% (weight).
If in the preparation skin composition, adopt the tretinoin activity inhibitor, in order to provide the order of magnitude, said composition can contain and accounts for said composition gross weight 0.001% to 15% (weight), the preferably inhibitor of 0.1% of the said composition gross weight to 10% (weight).
Usually it should be noted that above-mentioned all products can carry out the routine packing with the form that is suitable for selected administration of these products or application pattern (lotion, shampoo, tablet, syrup, nutritional supplement etc.).
Described compositions generally is to carry out the routine packing with the form that is suitable for different dosing or application pattern (lotion, shampoo, tablet, syrup, nutritional supplement etc.).So, preferably described compositions is packaged as the form that is fit to local coating.
Compositions of the present invention also can be mixed with various routines and common additive, especially sneaks into cosmetics additive in the situation (particularly hair product) of local coating, and described additive is selected from, for example UV screening agent; Thickening agent; Penetrating agent is as urea; Organic solvent is as ethanol, isopropyl alcohol or alkane glycol; Surfactant is selected from non-ionic surface active agent such as alkyl polysaccharide glycoside, cationic surfactant, anion surfactant and zwitterionic surfactant; Dyestuff; Dandruff removing agent, spice and antiseptic.
Need not to point out that the person of an ordinary skill in the technical field can select the chemical compound that adds in the compositions under the condition that does not influence beneficial effect of the present invention.
Slowing down and/or suppressing to have in the active known compositions product in a kind of field of and/or multiple hair growth and sneak into described chemical compound, also be fine.
In this, what can mention for example is cyclooxygenase-2 inhibitor and/or fat oxidation zymoexciter, for example is disclosed among patent application EP-A-94/402055, WO-A-94/27586 or the WO-A-94/27563 those.
Similarly, in a kind of field of and/or multiple alopecia, has active known compositions product and/or in alopeciaing therapeutic, have in the active product and can sneak into compositions of the present invention.
No matter described compositions can have active component with tretinoin activity inhibitor and other growth to a kind of and/or multiple hair and combine.Yet, can study specific embodiments, especially tretinoin activity inhibitor and other active component can be simultaneously, respectively or the order administration.
So, a theme of the present invention is the product that contains at least a tretinoin activity inhibitor and at least a other active components, this product be as simultaneously, respectively or be applied sequentially to slow down and/or suppress a kind of combination product of and/or multiple hair growth.
A theme of the present invention is the product that contains at least a tretinoin activity inhibitor and at least a other active components, this product be as simultaneously, respectively or be applied sequentially to slow down a kind of combination product of and/or multiple alopecia.
In a specific embodiments, tretinoin activity inhibitor and other active components can be packaged as the form of test kit respectively, the component in the test kit will mix in use.
A theme of the present invention is a kind of test kit that contains at least a tretinoin activity inhibitor and at least a other active components, and this test kit can be simultaneously, respectively or be applied sequentially to slow down and/or suppress a kind of and/or multiple hair growth.
The invention still further relates to a kind of test kit that contains at least a tretinoin activity inhibitor and at least a other active components, this test kit can be simultaneously, respectively or be applied sequentially to slow down coming off of a kind of and/or multiple hair.
According to the present invention, the consumption of tretinoin activity inhibitor can be 0.0001%-15% (weight) and preferred 0.01%-10% (weight).
Similarly, the consumption of cyclooxygenase-2 inhibitor or fat oxidation zymoexciter can be 0.001%-5% (weight) and preferred 0.01%-0.1% (weight).
According to another aspect of the present invention, a kind of non-therapeutic processing method that is used to slow down or prevent a kind of and/or multiple hair growth also is provided, this method comprises uses at least a dosage tretinoin activity inhibitor as defined above to body part and/or hydrophilic, and preferred described body is a human body.
According to another aspect of the present invention, a kind of non-therapeutic processing method that is used to slow down a kind of and/or multiple alopecia also is provided, this method comprises the tretinoin activity inhibitor that body part and/or at least a dosage of systemic administration are defined as mentioned, and preferred described body is a human body.
The preferred described tretinoin activity inhibitor of local application.
According to a particularly preferred embodiment of the method for the invention, definition compositions as above is coated on skin and/or the scalp.
In order to obtain appreciable effect, the administration number of times of the present composition or coating number of times are about 1 to 2 time of every days.In this, it should be noted that the abundant amount of inhibitor used among the present invention is generally still very little.
The present invention finds, it is effective especially that skin that infects in the multiple pathologic of treatment and/or scalp are particularly used the present composition aspect the hair follicle disease.
Now provide specific embodiment and illustrate the present invention.In context, described percentage ratio is based on the weight meter, unless otherwise indicated.
Embodiment 1:
It is resting stage (resting stage) the male C57BL6 mice in 42 day age that selection is in the hair cycle period.Scrape off their hair (DO) subsequently.Only occurring over just the hair that is in active stage because melanin is synthetic, is pink colour so shave the skin of mao mice.
Animal is divided into 2 groups, and 1 winding is contained the compositions of tretinoin activity inhibitor, and another group is handled with the used carrier of said composition.
Since the 1st day (D1), the above-mentioned composition of 50 μ l is coated in the skin area (3cm that shaves hair every day
3) in, the coating concentration of tretinoin activity inhibitor is 0.1%-0.3% (weight).
Observe every day and write down animal and every day the corresponding evaluation criteria of handling thus in the skin area.
Standard is as follows:
Standard 0: the skin of even pink colour
Standard 1: shaving the significant Lycoperdon polymorphum Vitt of appearance on the territory, hair-fields,
Standard 2: hair appears on the territory, hair-fields first shaving,
Standard 3: Lycoperdon polymorphum Vitt has covered the whole territory, hair-fields of shaving,
Standard 4: hair appears at the whole territory, hair-fields of shaving,
Standard 5: the hair of new piliation and other original places is as broad as long,
The results are shown in the following table.These results are equivalent to area under a curve, and described curve is corresponding to the time dependent function of each standard (longest term of observation: 90 days).
Table 1
| Standard | ??CD?2665 ??(0.1％) | ???CD?2848 ???(0.1％) | ????CD?2848 ????(0.3％) | Carrier |
| ????1 | ????7655 | ????7745 | ????7605 | ????7935 |
| ????2 | ????7425 | ????7455 | ????7270 | ????7660 |
| ????3 | ????6735 | ????6935 | ????6650 | ????7185 |
| ????4 | ????6445 | ????6605 | ????6325 | ????6865 |
| ????5 | ????3025 | ????2690 | ????1935 | ????3225 |
Table 2
| Standard | ????CD?2665 ????(0.1％) | ????CD?3106 ????(0.1％) | Carrier |
| ????1 | ????7972 | ????8031 | ????8422 |
| ????2 | ????7683 | ????7731 | ????8150 |
| ????3 | ????6900 | ????7131 | ????7606 |
| ????4 | ????6639 | ????6869 | ????7189 |
| ????5 | ????4850 | ????2450 | ????5506 |
Table 3
| Standard | ?CD?2665 ?(0.1％) | ????CD?2665 ????(0.3％) | ????CD?2822 ????(0.1％) | Carrier |
| ????1 | ????9235 | ????9535 | ????9635 | ????9650 |
| ????2 | ????9050 | ????9235 | ????9405 | ????9385 |
| ????3 | ????8005 | ????8500 | ????9105 | ????9065 |
| ????4 | ????7555 | ????8260 | ????8880 | ????8720 |
| ????5 | ????4335 | ????5200 | ????6465 | ????5485 |
CD2665 represent 4-[7-(the 1-adamantyl (and 6-methoxy ethoxy methoxyl group-2-naphthyl] benzoic acid,
CD2822 represent 6-[7-(the 1-adamantyl (and 6-methoxy ethoxy methoxyl group-2-naphthyl] nicotinic acid,
CD3106 represents 4-(5,5-dimethyl-8-is right-tolyl-5,6-dihydronaphthalene-2-ethyl-acetylene base) benzoic acid,
CD2848 represent 4-[7-(the 1-adamantyl (and 6-methoxy ethoxy methoxyl group-2-naphthyl] salicylic acid,
With the animal contrast with vehicle treated, restart and the elongated of animal individual hair of growth are obviously postponed in the animal of handling with the tretinoin activity inhibitor.
Embodiment 2:
Illustrate example of formulations of the present invention.These compositionss come together to obtain by different component is blended directly in.
Compositions 1: conservative washing liquid 4-[7-(the 1-adamantyl (6-methoxy ethoxy methoxyl group 1.0g-2-naphthyl] an amount of 100g of 22.8g95 ° of ethanol 55.1g of benzoic acid propylene glycol pure water
Compositions 2: rinsing type washing liquid 4-[7-(the 1-adamantyl (6-methoxy ethoxy methoxyl group 5.0g-2-naphthyl] an amount of 100g of salicylic acid propylene glycol 22.8g dehydrated alcohol
Compositions 3: conservative washing liquid 4-(5,5-dimethyl-8-is right-tolyl-5,6-dihydro 8.0g naphthalene-2-ethyl-acetylene base) benzoic acid, 95 ° of an amount of 100g of ethanol 55.1g pure water
Claims (12)
1. at least a tretinoin activity inhibitor or be used to prepare cosmetics or pharmaceutical composition, the application in the preferred skin composition, described compositions is the growth that is used to slow down and/or prevent a kind of and/or multiple hair.
2. at least a tretinoin activity inhibitor or be used to prepare cosmetics or pharmaceutical composition, the application in the preferred skin composition, described compositions is to be used to slow down coming off of a kind of and/or multiple hair.
3. according to the described application of above-mentioned each claim, it is characterized in that described tretinoin activity inhibitor is part or general administration.
4. according to the described application of above-mentioned each claim, it is characterized in that described tretinoin activity inhibitor is a topical.
5. according to the described application of above-mentioned each claim, it is characterized in that described tretinoin activity inhibitor is selected from:
-4-[7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl] benzoic acid,
-4-[7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl] salicylic acid,
-6-[7-(1-adamantyl)-6-methoxy ethoxy methoxyl group-2-naphthyl] nicotinic acid,
-4-{[5,6-dihydro-5,5-dimethyl-8-(4-aminomethyl phenyl)-2-naphthyl] acetenyl } benzoic acid,
-(E)-and 4-[2-(4,4-dimethyl-7-Oxy-1 in heptan, 1-dioxo-3,4-dihydro-2H-1-benzo thiapyran-6-yl) acrylic] benzoic acid,
-4-[4,5,7,8,9,10-six hydrogen-7,7,10,10-tetramethyl-1-(3-pyridylmethyl) anthra [1,2-b] pyrroles-3-yl] benzoic acid,
-4-[4,5,7,8,9,10-six hydrogen-7,7,10,10-tetramethyl-1-(3-pyridylmethyl) sulfo-anthra [1,2-b] pyrroles-3-yl] benzoic acid,
-4-[4,5,7,8,9,10-six hydrogen-7,7,10,10-tetramethyl-1-(3-pyridylmethyl) anthra [1,2-d] pyrazole-3-yl] benzoic acid,
-4-[3-(two adamantyls)-4-methoxybenzoyl amino] benzoic acid,
-4-[3-(two adamantyls)-4-methoxybenzoyl oxygen base] benzoic acid,
-4-(N-phenyl-5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl naphtho-[2,3-d] imidazoles-2-yl) benzoic acid,
-4-(N-benzyl-5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl naphtho-[2,3-d] imidazoles-2-yl) benzoic acid,
-4-(5H-7,8,9,10-tetrahydrochysene-5,7,7,10,10-pentamethyl benzo [c] naphtho-[2,3-b] [1,4] diaza -3-yl) benzoic acid,
-4-[1-(1-methoxyl group-2,2,2-trifluoroethyl)-5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl-3-anthryl] benzoic acid,
-4-(5,5-dimethyl-8-phenyl-5,6-dihydronaphthalene-2-ethyl-acetylene base) benzoic acid,
-4-(5,5-dimethyl-8-p-methylphenyl-5,6-dihydronaphthalene-2-ethyl-acetylene base) benzoic acid,
-4-[4-(biphenyl-2-yl) fourth-3-alkene-1-alkynyl] benzoic acid,
-(E)-4-[[3-oxo-3-[3-(1-adamantyl)-4-methoxy ethoxy methoxyphenyl]-the 1-acrylic]] benzoic acid.
6. according to the described application in cosmetic composition of above-mentioned each claim, the concentration that it is characterized in that described tretinoin activity inhibitor is the 0.0001%-5% (weight) of said composition gross weight, preferred 0.01%-2% (weight).
7. according to the described application in skin composition of each claim of claim 1-5, the concentration that it is characterized in that described tretinoin activity inhibitor is the 0.001%-15% (weight) of said composition gross weight, preferred 0.1%-10% (weight).
8. be used to slow down or prevent the non-therapeutic processing method of hair growth, this method comprises to body part and/or general uses the tretinoin activity inhibitor of at least a claim 1 and 3-6 definition.
9. be used to slow down a kind of non-therapeutic processing method of and/or multiple alopecia, this method comprises to body part and/or general uses the tretinoin activity inhibitor of at least a claim 2-6 definition.
10. be used for simultaneously, respectively or order slow down and/or suppress a kind of product of and/or multiple hair growth, it is characterized in that this product contains at least a tretinoin activity inhibitor and at least a other active components.
11. be used for the while, slow down a kind of product of and/or multiple alopecia respectively or in proper order, it is characterized in that this product contains at least a tretinoin activity inhibitor and at least a other active components.
12., it is characterized in that it is the form of test kit according to claim 10 or 11 described products.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9803978A FR2776511B1 (en) | 1998-03-31 | 1998-03-31 | USE IN OR FOR THE PREPARATION OF A COMPOSITION OF AT LEAST ONE INHIBITOR OF RETINOIC ACID ACTIVITY |
| FR98/03978 | 1998-03-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1298290A true CN1298290A (en) | 2001-06-06 |
Family
ID=9524693
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99804411A Pending CN1298290A (en) | 1998-03-31 | 1999-03-24 | Use of retinoic acid activity inhibitors to slow down hair loss |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP1066017A1 (en) |
| JP (1) | JP2002509870A (en) |
| KR (1) | KR20010042104A (en) |
| CN (1) | CN1298290A (en) |
| AR (1) | AR015551A1 (en) |
| AU (1) | AU2938899A (en) |
| BR (1) | BR9908411A (en) |
| CA (1) | CA2324899A1 (en) |
| FR (1) | FR2776511B1 (en) |
| HU (1) | HUP0102411A3 (en) |
| IL (1) | IL137859A0 (en) |
| NO (1) | NO20004880L (en) |
| PL (1) | PL343004A1 (en) |
| RU (1) | RU2193877C2 (en) |
| WO (1) | WO1999049838A1 (en) |
| ZA (1) | ZA200004483B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2733684B1 (en) * | 1995-05-03 | 1997-05-30 | Cird Galderma | USE OF RETINOIDS IN A COSMETIC COMPOSITION OR FOR THE MANUFACTURE OF A PHARMACEUTICAL COMPOSITION |
| FR2739777B1 (en) * | 1995-10-11 | 1997-11-14 | Cird Galderma | LIGAND ANTAGONIST RAR-GAMMA OR AGONIST RAR-ALPHA AS AN APOPTOSIS INHIBITOR |
| US5965606A (en) * | 1995-12-29 | 1999-10-12 | Allergan Sales, Inc. | Methods of treatment with compounds having RAR.sub.α receptor specific or selective activity |
| EP0889032A4 (en) * | 1996-03-18 | 2000-01-05 | Eisai Co Ltd | Fused-ring carboxylic acid derivatives |
-
1998
- 1998-03-31 FR FR9803978A patent/FR2776511B1/en not_active Expired - Fee Related
-
1999
- 1999-03-24 IL IL13785999A patent/IL137859A0/en unknown
- 1999-03-24 HU HU0102411A patent/HUP0102411A3/en unknown
- 1999-03-24 WO PCT/FR1999/000687 patent/WO1999049838A1/en not_active Application Discontinuation
- 1999-03-24 EP EP99910423A patent/EP1066017A1/en not_active Withdrawn
- 1999-03-24 PL PL99343004A patent/PL343004A1/en not_active Application Discontinuation
- 1999-03-24 JP JP2000540805A patent/JP2002509870A/en active Pending
- 1999-03-24 RU RU2000127111/14A patent/RU2193877C2/en active
- 1999-03-24 BR BR9908411-2A patent/BR9908411A/en not_active IP Right Cessation
- 1999-03-24 KR KR1020007010470A patent/KR20010042104A/en not_active Application Discontinuation
- 1999-03-24 CA CA002324899A patent/CA2324899A1/en not_active Abandoned
- 1999-03-24 AU AU29388/99A patent/AU2938899A/en not_active Abandoned
- 1999-03-24 CN CN99804411A patent/CN1298290A/en active Pending
- 1999-03-30 AR ARP990101412A patent/AR015551A1/en unknown
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2000
- 2000-08-29 ZA ZA200004483A patent/ZA200004483B/en unknown
- 2000-09-28 NO NO20004880A patent/NO20004880L/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2938899A (en) | 1999-10-18 |
| BR9908411A (en) | 2000-12-05 |
| KR20010042104A (en) | 2001-05-25 |
| JP2002509870A (en) | 2002-04-02 |
| AR015551A1 (en) | 2001-05-02 |
| PL343004A1 (en) | 2001-07-30 |
| HUP0102411A3 (en) | 2002-12-28 |
| NO20004880L (en) | 2000-11-30 |
| CA2324899A1 (en) | 1999-10-07 |
| FR2776511A1 (en) | 1999-10-01 |
| WO1999049838A1 (en) | 1999-10-07 |
| EP1066017A1 (en) | 2001-01-10 |
| HUP0102411A2 (en) | 2001-11-28 |
| RU2193877C2 (en) | 2002-12-10 |
| IL137859A0 (en) | 2001-10-31 |
| ZA200004483B (en) | 2002-02-27 |
| FR2776511B1 (en) | 2001-05-11 |
| NO20004880D0 (en) | 2000-09-28 |
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