EP1158975A1 - Verwendung von isoflavonen oder pygeumextract zur hemmung von 5ss-reductase - Google Patents

Verwendung von isoflavonen oder pygeumextract zur hemmung von 5ss-reductase

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Publication number
EP1158975A1
EP1158975A1 EP01907635A EP01907635A EP1158975A1 EP 1158975 A1 EP1158975 A1 EP 1158975A1 EP 01907635 A EP01907635 A EP 01907635A EP 01907635 A EP01907635 A EP 01907635A EP 1158975 A1 EP1158975 A1 EP 1158975A1
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EP
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Prior art keywords
composition
product
use according
isoflavones
extracts
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EP01907635A
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English (en)
French (fr)
Inventor
Philippe Msika
Antoine Piccirilli
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Laboratoires Expanscience SA
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Laboratoires Pharmascience SA
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Publication of EP1158975A1 publication Critical patent/EP1158975A1/de
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    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • 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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • 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
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • 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
    • A61P17/08—Antiseborrheics
    • 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
    • A61P17/10—Anti-acne agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • isoflavones and / or extracts of African plum for the preparation of a composition intended to inhibit the activity of 5 ⁇ -reductase, in pharmacy in particular in dermatology, in cosmetics and as a food additive.
  • the present invention relates to the use of at least one product chosen from the group consisting of isoflavones, extracts of African plum and mixtures thereof, for the preparation of a composition intended to inhibit the 5 ⁇ -reductase activity, in particular for the treatment of prostatic hypertrophy, prostatic adenoma, acne, hyperseborrhea, alopecia, hirsutism.
  • the invention also relates to cosmetic treatment methods, in particular for oily skin, as well as to the use of the products described as additives in a food for humans and / or animals.
  • 5 ⁇ -reductase is a microsomal NADPH dependent enzyme which exists in the form of two isoenzymes synthesized from two different genes.
  • the type 1 isoenzyme of 5 ⁇ -reductase is found mainly in the liver and skin, more particularly in the sebaceous glands of non-genital skin and scalp, and appears at puberty.
  • the type 2 isoenzyme is predominant in the prostate and in the skin of the differentiated sexual territories: genital area, beard, and plays a role in sexual differentiation.
  • Table 1 The distribution of type 1 and 2 isoenzymes of 5 ⁇ -reductase in the skin and the cutaneous appendages in humans can be illustrated by table 1 below.
  • Too high activity of 5 ⁇ -reductase thus causes too high levels of androgen in the form of DHT in the prostate, resulting in overstimulation of the latter resulting in a unwanted growth which can lead to the pathology of prostatic hypertrophy, or even to prostatic adenoma, most often requiring surgical intervention.
  • pathologies of dermatological type, can be observed in men or women as resulting from an overactivity of 5 ⁇ -reductase, namely, in particular acne, hirsutism or even alopecia.
  • the type 1 isoenzyme of 5-reductase in the sebaceous glands, as well as in the hair follicle.
  • the 5 ⁇ -reductase type 2 isoenzyme is localized mainly at the level of the internal epithelial sheath, as well as at the level of the dermal papilla of the hair. However, this latter location remains to be specified.
  • Androgenic alopecia whose pathophysiology is very close to that of acne, is the most common alopecia and probably the one where the demand for therapy is the highest. 5 ⁇ -reductase seems to play a key role in this pathology. Indeed, men suffering from a genetic deficiency in type 2 isoenzyme of 5 ⁇ -reductase do not develop androgenetic alopecia.
  • the extract of Serenoa Repens is also known, as a reference as a 5 ⁇ -reductase inhibitor, the extract of Serenoa Repens having the advantage, compared to finasteride, of a natural origin as plant extract allowing a better comparison for tested products also of natural origin.
  • Serenoa Repens also known as Sabal serrulatum, is a small palm that can be found in the United States (Florida) in North Africa and in Spain.
  • the present invention thus relates to the use of at least one product chosen from the group consisting of isoflavones, extracts of African plum and mixtures thereof, for the preparation of a composition intended to inhibit the 5 ⁇ -reductase type 1 activity
  • the expression “and the mixtures of the latter” above naturally includes in particular mixtures of isoflavones, mixtures of extracts of African plum or mixtures of isoflavones (s) and African plum extract (s).
  • composition is intended to inhibit the type 1 isoenzyme of 5 ⁇ -reductase
  • the isoflavones which can be used according to the invention can be obtained by chemical synthesis or are natural substances extracted from natural products, in particular from plants.
  • the isoflavones that can be used can also be a mixture of isoflavones of natural and synthetic origin.
  • R1 represents a hydrogen atom or a hydroxy group
  • R2 represents a hydrogen atom or a methoxy group
  • R6 represents a hydroxy group or a methoxy group. More particularly, RI, R2 and R6 can take the following meanings:
  • TAB 2, 4, 4'-trihydroxideoxybenzoine
  • isoflavones of aglycone form of formula (I) as defined above.
  • the glycosylated forms of isoflavones are hydrolyzed under the action of beta-glucosidases.
  • the glycosylated (daidzine and genistin) and acylated forms are the most abundant. Chemical or enzymatic acid hydrolysis can transform these conjugated forms into daidzein and genistein, which are more absorbable.
  • the use according to the invention is characterized in that the product is chosen from synthetic or natural isoflavones, from the group consisting of genistin, daidzin, glycitin, acetyldaidzin, acetylgenistin, acetylglycitin, malonyldaidzin, malonylgenistin, malonylglycitin, la 2,4,4'- trihydroxyoxybenzoine (THB), daidzein, genistein, glycitein, formononectin, biochanin A, genistein-4'-0-glucoside, 2'-hydroxygenistein- 7-0-glucoside, genistein-C-8-glucoside, and mixtures thereof.
  • TTB 2,4,4'- trihydroxyoxybenzoine
  • a product chosen from the group consisting of genistin, genistein and mixtures of the latter is particularly preferred to use according to the invention.
  • genistin genistein
  • mixtures of the latter there are no known natural sources as rich in isoflavones as soy.
  • the methods for purifying isoflavones from soy products, especially seeds, bean sprouts (or “sprouted soybeans"), soy milks including ground and molasses and fermented products (in particular Tofu and Tempeh) are good. known to those skilled in the art.
  • Table 2 below illustrates the isoflavone levels (micrograms / gram) in soybeans from Iowa crops (Wang and Murphy, "Isoflavone composition of American and Japanese Soybeans in Iowa: effects of variety, crop year, and location ", J. Agric. Food Chem. 1994, 42, 1674-1677).
  • Table 2 example of isoflavone contents in soybeans
  • soy milk it is traditionally obtained hot by grinding the seeds after skinning, in an alkaline medium. Heat treatment is performed to inhibit the antitrypsic factors.
  • the amounts of isoflavones present in soy milk are variable. Table 3 below is an illustration of the isoflavone contents of soy milk.
  • ground materials or molasses resulting from the production of soy milk also represent a source of soy isoflavones.
  • soy isoflavone extracts is thus meant according to the invention the soy isoflavone extracts obtained from the various soy products described above (seeds, soybeans (or “sprouted soybeans”), soy milks including ground and molasses and fermented products (in particular Tofu and Tempeh)), extracts which have optionally been purified and / or concentrated to increase their isoflavone contents, according to methods well known to those skilled in the art.
  • said product is chosen from extracts of soy isoflavones. Mention may in particular be made of the extract of soy isoflavones sold by the
  • Genosten 4000 R is a soluble soy extract enriched with isoflavones obtained after concentration by successive evaporations of the soy molasses. This process does not use any organic solvent. Analytical data for this product can be found in the examples below.
  • Lupine is also an interesting natural source of isoflavones. Mention may in particular be made of the variety of "yellow lupine” in the stems of which the glycosylated isoflavones genistin, 2'-hydroxygenistein-7-0-glucoside, genistein-4'-0-glucoside and genistein-C have been identified. 8-glucoside, the respective formulas of which are described above (Rafal Franski et al, "Application of mass spectrometry to structural identification of flavonoid monoglycosides isolated from shoot of lupine (lupinus luteus L.)", Acta Biochimica Polonica, vol. 46, N ° 2/1999, 459-473).
  • the use according to the invention is thus also characterized in that the product is chosen from extracts of isoflavones of lupine, that is to say, by analogy with the definition above for extracts of isoflavones of soybeans , among the extracts of isoflavones which can be obtained from lupine products.
  • the extracts of African plum or "Pygeum Africanum” are well known to those skilled in the art. They are mainly made from the bark of the African plum tree. These are sterolic extracts of African plum, such as that sold by the company Euromed under the name "Pygeum”.
  • the African plum extract has the following fatty acid weight distribution: from 30 to 40% in oleic acid, from 7 to 12% in linoleic acid, from 40 to 55% in palmitic acid and less than 3% in linolenic acid.
  • the sterol content is between 13 and 18% and the overall acid number of the extract is less than 45.
  • the plum extract which is further characterized by a relative ⁇ -sitosterol content of 65 to 80%.
  • the plum extract is preferred, which is further characterized by an unsaponifiable content of 15 to 18%.
  • the plum extract suitable for use according to the present invention can for example have the following specifications:
  • the product as described above is used according to the invention, in the form of soy isoflavone (s), African plum extract (s) or a mixture of these, according to a proportion of between approximately 0.001 and approximately 100% by weight (use in pure form possible of the said product), preferably between approximately 0.01 and approximately 70% by weight, and more particularly still between approximately 0.1 and 10% by weight, relative to the total weight of the composition.
  • composition prepared by the use according to the invention can also comprise a pharmaceutically, dermatologically or cosmetically acceptable excipient.
  • Any excipient suitable for the dosage forms known to those skilled in the art can be used, for administration by topical, oral, enteral or parenteral, in particular rectal route.
  • this excipient can be adapted for obtaining a composition in the form of an oily solution, of a water-in-oil emulsion, an emulsion oil-in-water, a microemulsion, an oily gel, an anhydrous gel, a cream, a dispersion of vesicles, microcapsules or microparticles, or even gelatin or vegetable soft capsules or capsules.
  • an excipient suitable for administration by the external topical route or by the rectal route is used.
  • the advantageous effect of inhibiting the activity of the 5 ⁇ -reductase type 1 provided by the use according to the invention makes it possible to use the composition thus prepared for therapeutic treatments, notably dermatological, and cosmetic.
  • the use according to the invention is characterized in that the composition is intended for the treatment of pathologies and / or skin disorders linked to a congenital exaggeration or acquired from the activity of type 1 5 ⁇ -reductase.
  • composition is intended for the treatment of acne.
  • composition is intended for the treatment of hyperseborrhea.
  • composition is intended for the treatment of alopecia.
  • the use according to the invention is also characterized in that the composition is intended for the treatment of hirsutism.
  • the present invention also relates to a cosmetic treatment method for oily skin, characterized in that a cosmetic composition is applied to the skin containing at least one product chosen from the group consisting of isoflavones, plum extracts of Africa as defined above and mixtures of these, as described above.
  • a subject of the invention is also a method of cosmetic treatment for hair loss, characterized in that a cosmetic composition is applied to the scalp containing at least one product chosen from the group consisting of isoflavones, extracts of African plum as defined above and mixtures thereof, as described above.
  • the subject of the invention is also a method of cosmetic treatment of excess hairiness, characterized in that it is applied to the areas of the skin with excess hairiness a cosmetic composition containing at least one product chosen from the group consisting of isoflavones, African plum extracts as defined above and mixtures of these, as described above.
  • a cosmetic composition containing at least one product chosen from the group consisting of isoflavones, African plum extracts as defined above and mixtures of these, as described above.
  • these last two cosmetic treatment methods make it possible to improve the appearance by visibly reducing the unsightly phenomena of hair loss linked to alopecia and the phenomena of excess pilosity linked to hirsutism.
  • said product is present in the composition in a proportion of between approximately 0.001 and approximately 100% by weight (use in pure form possible, without excipient), preferably between approximately 0.01 and approximately 70% by weight, and more particularly still between approximately 0.1 and 10% by weight, relative to the total weight of the composition.
  • the cosmetic composition applied according to the cosmetic method of the invention also contains at least one cosmetically acceptable excipient as described above.
  • Another subject of the invention is the use of at least one compound chosen from the group consisting of isoflavones, African plum extracts as defined above and mixtures of the latter, as described below. above, as an additive in food for humans and / or animals.
  • This food use is preferably characterized in that said additive is present in the food in a proportion of between approximately 0.001 and approximately 100% by weight, preferably between approximately 0.01 and approximately 70% by weight, and more particularly still between about 0, 1 and 10% by weight, relative to the total weight of the food.
  • the invention also relates to the use of extracts of African plum as defined above for the preparation of a composition intended to inhibit the activity of type 2 5 ⁇ -reductase.
  • Another subject of the invention is also the use of extracts of African plum as defined above for the preparation of a composition intended for the treatment of prostatic hypertrophy.
  • extracts of African plum as defined above can be used for the preparation of a composition intended for the treatment and of prostatic adenoma, and in particular for the preparation of such a composition for the administration rectally.
  • Genosten 4000 The soy isoflavone extract tested, called Genosten 4000, was supplied by the company Nutrinov.
  • Soluble soy extract enriched with isoflavones obtained by a physical extraction technique, without the use of organic solvents.
  • Total isoflavone content 4000 +/- 200 mg / 100 g
  • Typical profile Daidzine 200 Genistin 280 Malonyldaidzine 900
  • the Pygeum Africanum extract tested was supplied by the company Euromed.
  • Lipido-sterolic extract of Pygeum Africanum from pygeum bark Lipido-sterolic extract of Pygeum Africanum from pygeum bark.
  • Example 1 Evaluation of the inhibitory activity on the activity of 5 ⁇ -reductase by measuring the level of 5-dihydrotestosterone formed from testosterone by DU145 cells.
  • Prostate DU 145 cells are from a tumor line obtained from a carcinoma of the prostate (ATCC number HTB 81).
  • MEM medium (ref. 0410265), glutamine and gentamycin come from Gibco.
  • Fetal calf serum (SVF) comes from DAP and is used decomplemented (45 mm at 56 ° C). the plastics used for cultivation (boxes and plates) come from Costar. Testosterone comes from Sigma.
  • a stock solution of ethanol at 10 mg / ml is prepared from each of the products tested.
  • the concentration range used for the experiments is as follows: 0, 5, 10, 50, 100 and 500 micrograms / ml. (Dilution carried out in the culture medium). The volume of extract added per well being 20 microliters / well, the solutions to be prepared are concentrated 50X.
  • a 10 mM testosterone stock solution is prepared in ethanol. At the time of use, this solution is diluted 1: 1000 in the culture medium and 10 microliters are added per well.
  • Prostatic DU 145 cells are cultured at 37 ° C., 5% CO 2 in MEM medium containing glutamine (2 mM), gentamycin (50 micrograms / ml) and 10% of SNF. Their subculture rate is 1:10.
  • the cells are cultured in 6-well plates at the rate of 2.10 * 5 DU 145 per well / 1 ml of medium containing only 1% of SNF.
  • the cells are maintained for 3 days at 37 ° C., 5% CO 2.
  • the culture medium contained in the wells is eliminated and replaced by new medium containing 1% SNF.
  • Testosterone (0.1 micromolar final) as well as the extracts at different concentrations are added to the medium at the rate of 10 and 20 microliters / well respectively.
  • the "control" wells correspond to cells incubated in the presence of testosterone and an Ethanol equivalent. This makes it possible to subtract the effect of the solvent on the cultures and to determine the percentage of DHT formed in the absence of inhibitor).
  • the cells are then incubated at 37 ° C, 5% CO2. After 3 hours, the culture supernatants are collected and frozen at -80 ° C until the assay.
  • the extract of Serenoa Repens chosen as a reference substance, inhibits the activity of 5-alpha reductase. This result therefore validates the test.
  • the Pygeum Africanum extract tested is active in the inhibition of 5-alpha reductase.
  • MCF fibroblast culture medium
  • MEM designation given to the culture medium, Minimum Essential medium
  • 5 ⁇ -DHT 5 ⁇ -dihydrotestosterone
  • products such as an extract of soy isoflavones (Genosten 4000, described above), genistein and genistin (purified isoflavones, commercial products Sigma), a extract of Pygeum Africanum, of an extract of Serenoa Repens chosen as reference, on the activity of 5 ⁇ -reductase.
  • An in vitro model of normal human dermal fibroblast cultures was chosen.
  • test products were supplied by EXPANSCIENCE and were stored at + 4 ° C until the time of their use.
  • Radioactive testosterone (labeled with tritium in position 1, 2, 6 and 7, specific activity 79 Ci / mmol) was supplied by AMERSHAM, non-radiolabelled testosterone was supplied by SIGMA.
  • Analytical quality reagents came from SIGMA, MERCK,
  • the fibroblast culture medium consisted of MEM / M199 (3: 1, v / v) supplemented with penicillin (50 IU / ml), streptomycin (50 ⁇ g / ml), sodium bicarbonate (0 , 2%, w / v) and SNF (10%, v / v).
  • the test system consisted of normal human dermal fibroblasts grown in a monolayer.
  • the fibroblasts were isolated from a residue of abdominal plasty performed on a 51-year-old woman (subject BIOPREDIC n ° I0013).
  • the cells were used on the fifth passage, they were cultured until the monolayers converge in the MCF medium at 37 ° C. in a humid atmosphere containing 5% CO 2 .
  • the fibroblast incubation medium consisted of MCF supplemented with tritiated testosterone (1.6 x 10 '7 M, or 6.32 ⁇ Ci / ml) and non-radiolabelled testosterone (3.84 x 10 "6 M).
  • tritiated testosterone 1.6 x 10 '7 M, or 6.32 ⁇ Ci / ml
  • non-radiolabelled testosterone 3.84 x 10 "6 M
  • the test products and the finasteride were taken up in DMSO before being diluted in the incubation medium.
  • the final concentration of DMSO was kept constant and equal to 1% (v / v) in each dilution of test and reference products.
  • the fibroblast cultures were pre-incubated in the presence of the test products or of the reference product for 2 hours before the addition of the substrate, testosterone.
  • the test products and the reference product were prepared in the MCF medium.
  • the fibroblast cultures were incubated in the presence of the test products or of the reference product prepared in the MIF medium for 22 hours (or 24 hours, indicated with the results) at 37 ° C. in a humid atmosphere containing 5% CO 2 . Control cultures were incubated in the MIF medium in the absence of test products and of reference product.
  • DMSO control were incubated in MIF medium containing 1% (v / v) of DMSO. Each experimental condition was tested in triplicate.
  • the cells were subjected to the action of ultrasound in the MIF medium.
  • the cell lysates thus obtained were extracted with dichloromethane. After evaporation, the dry residues were taken up in methanol and were deposited on silica plates 60F 25 (MERCK, reference 5554).
  • the metabolism of testosterone to 5 ⁇ -dihydrotestosterone under the various experimental conditions was calculated: the results (areas of the peaks of 5 ⁇ -dihydrotestosterone counted by the BERTHOLD scanner) were expressed in pmoles of 5 ⁇ -dihydrotestosterone formed by culture well. They were also expressed as a percentage of the 5 ⁇ -reductase activity present in the 'DMSO control' group.
  • the data groups (control group and treated groups) were treated by a factor analysis of variance (ANONA 1, p ⁇ 0.05), followed by a DU ⁇ ETT test (p ⁇ 0.05).
  • the effect of the test and reference products was compared with the 'DMSO control' group.
  • Genistein tested at 0.1; 1 and 10 ⁇ g / ml, significantly inhibited (p ⁇ 0.05) by 32%; 33% and 31% respectively the activity of 5 ⁇ -reductase. At 100 ⁇ g / ml, it significantly inhibited (p ⁇ 0.05) by 61% the activity of 5 ⁇ -reductase.
  • soy isoflavone extract tested at 10 and 100 ⁇ g / ml, inhibited the activity of 5 ⁇ -reductase by 22 and 17% respectively.
  • the Serenoa Repens extract tested at 10 and 100 ⁇ g / ml, inhibited the activity of 5 ⁇ -reductase by 15 and 35% respectively. At 1 ⁇ g / ml, it had no effect.
  • the Serenoa Repens extract tested at 10 and 100 ⁇ g / ml, inhibited the activity of 5 ⁇ -reductase by 15 and 35% respectively. At 1 ⁇ g / ml, it had no effect (table paragraph 3.3.2).
  • the results are expressed in pmoles of 5 ⁇ -DHT formed / culture well.
  • the results are expressed in pmoles of 5 ⁇ -DHT formed / culture well.
  • the results are expressed in pmoles of 5 ⁇ -DHT formed / culture well.
  • the results are expressed in pmoles of 5 ⁇ -DHT formed / culture well.
  • Example 3 composition of a shampoo for oily hair.
  • Soy Isoflavone 2,000 EXAMPLE 5 Composition of an Emulsion for Oily Skin

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EP01907635A 2000-01-18 2001-01-18 Verwendung von isoflavonen oder pygeumextract zur hemmung von 5ss-reductase Withdrawn EP1158975A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0000573A FR2803747B1 (fr) 2000-01-18 2000-01-18 Utilisation d'isoflavones et/ou d'extraits de prunier d'afrique en pharmacie, cosmetique et en tant qu'additif alimentaire.
FR0000573 2000-01-18
PCT/FR2001/000170 WO2001052840A1 (fr) 2000-01-18 2001-01-18 UTILISATION D'ISOFLAVONES ET/OU D'EXTRAITS DE PRUNIER D'AFRIQUE POUR LA PREPARATION D'UNE COMPOSITION DESTINEE A INHIBER L'ACTIVITE DE LA 5α-REDUCTASE, EN PHARMACIE NOTAMMENT EN DERMATOLOGIE, EN COSMETIQUE ET EN TANT QU'ADDITIF ALIMENTAIRE

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EP1158975A1 true EP1158975A1 (de) 2001-12-05

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EP01907635A Withdrawn EP1158975A1 (de) 2000-01-18 2001-01-18 Verwendung von isoflavonen oder pygeumextract zur hemmung von 5ss-reductase

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EP (1) EP1158975A1 (de)
AU (1) AU3555101A (de)
FR (1) FR2803747B1 (de)
WO (1) WO2001052840A1 (de)

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US8039026B1 (en) 1997-07-28 2011-10-18 Johnson & Johnson Consumer Companies, Inc Methods for treating skin pigmentation
US8106094B2 (en) 1998-07-06 2012-01-31 Johnson & Johnson Consumer Companies, Inc. Compositions and methods for treating skin conditions
US8093293B2 (en) 1998-07-06 2012-01-10 Johnson & Johnson Consumer Companies, Inc. Methods for treating skin conditions
US7985404B1 (en) * 1999-07-27 2011-07-26 Johnson & Johnson Consumer Companies, Inc. Reducing hair growth, hair follicle and hair shaft size and hair pigmentation
WO2001074345A2 (en) * 2000-03-31 2001-10-11 Jonathan Ingram Isoflavones for treatment of obesity
US8431550B2 (en) 2000-10-27 2013-04-30 Johnson & Johnson Consumer Companies, Inc. Topical anti-cancer compositions and methods of use thereof
US7192615B2 (en) 2001-02-28 2007-03-20 J&J Consumer Companies, Inc. Compositions containing legume products
DE10114305A1 (de) * 2001-03-23 2002-09-26 Beiersdorf Ag Kosmetische und dermatologische Zubereitungen mit einem Gehalt an Isoflavonen und Verwendung von Isoflavonen zur Herstellung kosmetischer und dermatologischer Zubereitungen zur Reduktion des Sebumgehaltes der Haut
JP2007526297A (ja) * 2004-03-02 2007-09-13 ジュリアーニ ソシエタ ペル アチオニ 毛嚢のトロフィズム及び皮脂の皮膚形成を調整するための組成物及びアンドロゲン性脱毛症におけるそれらの使用
CZ302596B6 (cs) * 2007-04-12 2011-07-27 Jihoceská univerzita v Ceských Budejovicích, Zemedelská fakulta Zpusob zpracování biomasy jetele lucního
CN108997453B (zh) * 2018-07-20 2021-01-01 四川省中医药科学院 一种二苯乙酮苷类化合物及其制备方法和用途
CN111643511A (zh) * 2020-07-27 2020-09-11 吉林省现代中药工程研究中心有限公司 槐角苷在制备防治前列腺疾病的药物中的应用

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JP2791673B2 (ja) * 1989-01-23 1998-08-27 花王株式会社 ５α―リダクターゼ阻害剤
US5543146A (en) * 1995-01-20 1996-08-06 Prostahelp, Inc. Dietary supplement for alleviating the symptoms associated with enlargement of the prostate gland
JP3978250B2 (ja) * 1996-08-16 2007-09-19 株式会社フジモト・コーポレーション テストステロン５α−リダクターゼ阻害剤
US6576660B1 (en) * 1997-10-31 2003-06-10 Arch Development Corporation Methods and compositions for regulation of 5-α-reductase activity
US5972345A (en) * 1999-05-03 1999-10-26 Chizick; Stephen Natural preparation for treatment of male pattern hair loss

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FR2803747B1 (fr) 2003-12-26
WO2001052840A1 (fr) 2001-07-26
FR2803747A1 (fr) 2001-07-20
AU3555101A (en) 2001-07-31

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