Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
• • 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
  • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
  • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
  • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
• • 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
  • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• • 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
  • A61K8/37—Esters of carboxylic acids
• • 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
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • 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
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q7/00—Preparations for affecting hair growth
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
  • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
  • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
  • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
  • C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
  • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
  • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings

Definitions

• the present invention relates to a composition and method for promoting hair growth in a mammalian subject.
• BACKGROUND ART Hair loss or alopecia may result from genetic factors, aging, local or systemic disease or certain therapeutic drugs designed to alleviate conditions such as cancer.
• Various preparations for preventing or reducing hair loss and/or promoting hair growth are proposed, for example those containing female hormones which can promote blood circulation, reinforce hair root function, moisturize scalp and inhibit male hormone function; 5 ⁇ -reductase inhibitors; or inoxdil, trichosaccharid.es __ or . the like as main ingredients.
• Prostaglandins hereinafter, referred to as
• PG(s) are members of class of organic carboxylic acids, which are contained in tissues or organs of human or other mammals, and exhibit a wide range of physiological activity.
• PGs found in nature (primary PGs) generally have a prostanoic acid skeleton as shown in the formula (A) ( chain)
• the primary PGs are classified to PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, ' PGHs, PGIs and PGJs according to the structure of the five- membered ring moiety, and further classified into the following three types by the number and position of the unsaturated bond at the carbon chain moiety: Subscript 1: 13, 14-unsaturated-15-OH Subscript 2: 5,6- and 13, 14-diunsaturated-15-OH Subscript 3: 5,6-, 13,14-, and 17, 18-triunsaturated- 15-OH.
• the PGFs are classified, according to the configuration of the hydroxyl group at the 9- and 11- position, into . type (the hydroxyl group is of an - configuration) and ⁇ type (the hydroxyl group is of a ⁇ - configuration) .
• type the hydroxyl group is of an - configuration
• ⁇ type the hydroxyl group is of a ⁇ - configuration
• No. 4,088,775 discloses certain 15-ethylenedioxy-prostanoic acid.
• US patent No. 4,870,104 discloses 11 halo prostaglandins which may have an ethylenedioxymethylene group at 15-position and use thereof as agents inhibiting gastric acid secretion.
• US patent No. 6,353,014 discloses a certain 15-ketal analogs of F series prostaglandins useful for treating ocular hypertension and glaucoma. Those prior arts do not disclose nor suggest that prostaglandin compound having two hetero atoms at the 15 position may be useful in the stimulation of hair growth.
• An object of the present invention is to provide a composition for promoting hair growth in a mammalian subject.
• - Further object of the present invention is to provide a method for promoting hair growth in a mammalian subject.
• Still further object of the present invention is to provide a novel compound useful for promoting hair growth in a mammalian subject.
• the present invention relates to a composition for promoting hair growth in a mammalian subject which comprises a prostaglandin compound having two hetero atoms at the- 15 position as an active ingredient thereof.
• the present invention relates to a method for promoting hair growth in a mammalian subject, which comprises topically administering a prostaglandin compound having two hetero atoms at the 15 position to the subject in need thereof. Furthermore, the present invention relates to use of a prostaglandin compound having two hetero atoms at the 15 position -for manufacturing a composition for promoting hair growth in a mammalian subject. Still further, the present invention relates to a novel prostaglandin compound having two hetero atoms at the 15 position. DETAILED DESCRIPTION OF THE INVENTION The nomenclature of the PG compounds used herein is based- on the numbering system of the prostanoic acid represented in the above formula (A) .
• the formula (A) shows a basic skeleton of the C- 20 carbon atoms, but the present invention is not limited to those having the same number of carbon atoms.
• the numbering of the carbon atoms which constitute the basic skeleton of the PG compounds starts at the carboxylic acid (numbered 1), and carbon atoms in the ⁇ -chain are numbered 2 to 7 towards the five-me bered ring, those in the ring are 8 to 12, and those in the co-chain are 13 to 20.
• a PG compound of which ⁇ -chain is extended by two carbon atoms, that is, having 9 carbon atoms in the ⁇ -chain is named as 2 ⁇ decarboxy-2- (2-carboxyethyl) -PG compound.
• a PG compound having 11 carbon atoms in the ⁇ -chain is named as 2-decarboxy-2- (4-carboxybutyl) - PG compound.
• a PG compound of which ⁇ -chain is extended by two carbon atoms, that is, having 10 carbon atoms in the ⁇ -chain is named as 20-ethyl-PG compound.
• These compounds ⁇ however, may also be named according to the IUPAC nomenclatures. Examples of the analogs (including substituted derivatives) or.
• derivatives include a PG compound of which carboxyl group at the end of ⁇ -chain is esterified; -a compound of which ⁇ -chain is extended; physiologically acceptable salt thereof; a compound having a double bond at 2-3 position-, or a triple bond at position 5-6, a compound. having substituent (s) at position 3, 5, 6, 16, 17, 18, 19 and/or 20; and a compound having lower alkyl or a hydroxy
• substituents at position 3, 17, 18 and/or 19 include alkyl having 1-4 carbon atoms, especially methyl and ethyl.
• Preferred substituents at position 16 include lower alkyl such as methyl and ethyl, hydroxy, halogen atoms such as chlorine and fluorine, and aryloxy such as trifluoromethylphenoxy.
• Preferred substituents at position 17 include lower alkyl such as methyl and ethyl, hydroxy, halogen atoms such as chlorine and fluorine, aryloxy such as trifluoromethylphenoxy.
• Preferred substituents at position 20 include saturated or unsaturated lower alkyl such as Cl-4 alkyl, lower alkoxy such as Cl-4 alkoxy, and lower alkoxy alkyl such as Cl-4 alkoxy-Cl-4 alkyl.
• Preferred substuents at position 5 include halogen atoms such as chlorine and fluorine.
• Preferred substituents at position 6 include an oxo group forming a carbonyl group.
• Stereochemistry of PGs having hydroxy, lower alkyl or hydroxy,(lower) alkyl substituent at position.9. and/or 11 may be ⁇ , ⁇ or a mixture -thereof.
• the above analogs or derivatives may be compounds having an alkoxy, cycloalkyl,. cycloalkyloxy, phenoxy or phenyl group at the end of the ⁇ -chain where the chain is shorter than the primary PGs.
• a preferred prostaglandin compound used in the present invention is represented by formula (I)
• L, M and N are hydrogen, hydroxy, halogen, lower alkyl, hydroxy (lower) alkyl, lower alkanoyloxy or oxo, wherein at least one of L and M is a group other than -hydrogen, and the five-membered ring may have at least one double bond;
• A is -CH 3 , or -CH 2 OH, -COCH 2 OH, -COOH or a functional derivative thereof;
• Zi and Z 2 are oxygen, nitrogen or sulfur,
• R 2 and R 3 are optionally substituted lower alkyl, which is optionally linked together to form lower alkylene,
• Ri is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, alkyl, hydroxy, oxo, aryl or heterocyclic group, and at least one of carbon
• L and M are hydrogen, hydroxy, halogen, lower alkyl, .hydrox (lower) alkyl, lower alkanoyloxy or oxo, wherein at least one of L and M is a group other than hydrogen, and the five-membered ring may have one or more double bonds;
• A is -CH 3 or -CH 2 OH, -COCH2OH, -COOH or a functional derivative thereof;
• Zi and Z 2 are oxygen, nitrogen or sulfur, R 2 and R 3 are optionally substituted lower alkyl, which is optionally linked together to form lower alkylene,
• Xi and X 2 are hydrogen, lower alkyl, or halogen;
• Ri is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, alkyl, hydroxy, ox
• the term "unsaturated" in the definitions for Ri and Ra is intended to include at least one or more double bonds and/or triple bonds that are isolatedly, separately or serially present between carbon atoms of the main and/or side chains. -According to the usual nomenclature, an unsaturated bond between two serial positions is represented by denoting the lower number of the two positions, and an unsaturated bond between two distal positions is represented by denoting both of the positions .
• the term “lower or medium aliphatic hydrocarbon” refers to a straight or branched chain hydrocarbon group having 1 to 14 carbon atoms (for ' a side chain, 1 to 3 carbon atoms are preferable) and preferably 1 to 10, especially 1 to 8 carbon atoms.
• halogen atom covers fluorine, chlorine,
• lower throughout the specification is intended to include a group having 1 to 6 carbon atoms unless otherwise specified.
• lower alkyl refers to a straight or branched chain saturated hydrocarbon ' group containing 1 to 6 carbon atoms and includes, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, ⁇ t-butyl, pentyl and hexyl .
• lower alkylene refers to a straight or branched chain bivalent saturated hydrocarbon group containing 1 to 6 carbon atoms and includes, for example, methylene, ethylene, propylene, isopropylene, butylene, isobutylene, t-butylene, pentylene and hexylene.
• lower alkoxy refers to a group of lower alkyl-O-, wherein lower alkyl is as defined above.
• hydroxy (lower) alkyl refers to a lower alkyl as defined above which is substituted with at least one hydroxy group such as hydroxymethyl, 1-hydroxyethyl, 2- hydroxyethyl and 1-methyl-l-hydroxyethyl .
• lower alkanoyloxy refers to a group represented by the formula RCO-0-, wherein RCO- is an acyl group formed by oxidation of a lower alkyl group as defined above, such as acetyl.
• cyclo (lower) alkyl refers to a cyclic group formed by cyclization of a lower alkyl group as defined above but contains three or more carbon atoms, and includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
• cyclo (lower) alkyloxy refers to the group of cyclo (lower) alkyl-O-, wherein cyclo (lower) alkyl is as defined above.
• aryl may include unsubstituted or substituted aromatic hydrocarbon rings (preferably monocyclic groups), for example, phenyl, tolyl, xylyl. Examples of the substituents are halogen atom and halo (lower) alkyl, wherein halogen atom and lower alkyl are as defined above.
• aryloxy refers to a group represented by the formula ArO-, wherein Ar is aryl as defined above.
• heterocyclic group may include mono- to tri-cyclic, preferably monocyclic heterocyclic group which is 5 to 14, preferably 5 to 10 membered ring having optionally substituted carbon atom and 1 to 4, preferably 1 to 3 of 1 or 2 type of hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom.
• heterocyclic group examples include furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, i idazolyl, pyrazolyl, furazanyl, pyranyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, 2-pyrrolinyl, pyrrolidinyl, 2- imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, piperidino, piperazinyl, orpholino, indolyl, benzothienyl, quinolyl, isoquinolyl, purinyl, quinazolinyl, carbazolyl, acridinyl, phenanthridinyl, benzi idazolyl, benzimidazolinyl, benzothiazolyl,
• substituents in this case include halogen, and halogen substituted lower alkyl group, wherein halogen atom and lower alkyl group are as described above.
• heterocyclic-oxy group means a group represented by the formula HcO-, wherein He is a heterocyclic group as described above.
• functional derivative of A includes salts (preferably pharmaceutically acceptable salts) , ethers, esters and amides.
• Suitable "pharmaceutically acceptable salts” include conventionally used non-toxic salts, for example a salt with an inorganic base such as an alkali metal salt (such as sodium salt and potassium salt) , an alkaline earth metal salt (such as calcium salt and magnesium salt), an ammonium salt; or a salt with an organic base, for example, an amine salt (such as methylamine salt, dimethylamine salt, cyclohexylamine salt, benzylamine salt, piperidine salt, ethylenediamine salt, ethanolamine salt, diethanolamine salt, triethanolamine salt, tris (hydroxymethylamino) ethane salt, monomethyl- monoethanolamine salt, procaine salt and caffeine salt), a basic a ino acid salt (such as arginine salt and lysine salt) , tetraalkyl ammonium salt and the like.
• an inorganic base such as an alkali metal salt (such as sodium salt and potassium salt) , an alkaline earth metal salt (such as
• ethers examples include alkyl ethers, for example, lower alkyl ethers such as . methyl ether, ethyl ether, propyl ether, isopropyl ether, butyl ether, isobutyl ether, t-butyl ether, pentyl ether and 1-cyclopropyl ethyl ether; .
• lower alkyl ethers such as . methyl ether, ethyl ether, propyl ether, isopropyl ether, butyl ether, isobutyl ether, t-butyl ether, pentyl ether and 1-cyclopropyl ethyl ether; .
• alkyl ethers such as octyl ether, diethylhexyl ether, lauryl ether and cetyl ether; unsaturated ethers such as oleyl ether and linolenyl ether; lower alkenyl ethers such as vinyl ether, allyl ether; lower alkynyl ethers such as ethynyl ether and propynyl ether; hydroxy (lower) alkyl ethers such as hydroxyethyl ether and hydroxyisopropyl ether; lower alkoxy (lower) alkyl ethers such as methoxymethyl ether and 1-methoxyethyl ether; optionally substituted aryl ethers such as phenyl ether, tosyl ether, t-butylphenyl ether, salicyl ether, 3, 4-di-methoxyphenyl ether and benzamidophenyl ether;
• esters examples include aliphatic esters, for example, lower alkyl esters such as methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, t-butyl ester, pentyl ester and 1-cyclopropylethyl ester; lower alkenyl esters such as vinyl ester and allyl ester; lower alkynyl esters such as ethynyl ester and propynyl ester; hydroxy (lower) alkyl ester such as hydroxyethyl ester; lower alkoxy (lower) alkyl esters such as ethoxymethyl ester and 1-methoxyethyl ester; and optionally, substituted aryl esters such as,, for example, phenyl ester, tolyl ester, t-butylphenyl ester, salicyl ester, 3, 4-di-methoxyphenyl
• the amide of A mean a group represented by the ' formula -CONR'R", wherein each of R' and R" is hydrogen, lower alkyl, aryl, alkyl- or aryl-sulfonyl, lower alkenyl and lower alkynyl, and include for example lower alkyl amides such as methylamide, ethylamide, dimethylamide and diethylamide; arylamides such as anilide and toluidide; and alkyl- or aryl-sulfonyla ides such as ethylsulfonylamide, ethylsulfonyl-amide and tolylsulfonylamide.
• lower alkyl amides such as methylamide, ethylamide, dimethylamide and diethylamide
• arylamides such as anilide and toluidide
• alkyl- or aryl-sulfonyla ides such as ethyl
• L and M include hydroxy and oxo, and especially, M and L are hydroxy groups which has a 5-membered ring structure of, so called, PGF type.
• PGF type Preferred example of A is -COOH, its pharmaceutically acceptable salt, ester or amide thereof.
• Preferred B is -CH 2 -CH 2 -, so called 13, 14-dihydro type.
• Preferred example of Xi and X 2 is fluorine, so called 16, 16-difluoro type.
• R x is a hydrocarbon residue containing 1-10 carbon atoms, preferably 6-10 carbon atoms.
• At least one - carbon atom in the aliphatic hydrocarbon is optionally substituted by oxygen, nitrogen or sulfur-
• Ra is a hydrocarbon containing 1-10 carbon atoms, more preferably, 1-8 carbon atoms. Ra may have one -or two side chains having one carbon atom.
• - Preferred Zi and Z 2 are oxygen.
• R 2 and R 3 are preferably linked together to form C2 or C3 alkylene.
• the configuration of the ring and the ⁇ - and/or ⁇ chains in the above formula (I) -and (II) may be the same as or different from that of the primary PGs.
• the present invention also includes a mixture of a compound having a primary type configuration and a compound of a non-primary type configuration.
• any of isomers such- as the individual tautomeric isomers, the mixture thereof, or optical isomers, the mixture thereof, a racemic- mixture, and other steric isomers may be used in the same purpose.
• a composition for promoting hair growth comprising the prostaglandin compound defined as above as an active ingredient is applied to a mammalian subject in need of promotion of hair growth.
• hair in the present specification and claims covers any hair on a mammalian subject, especially a human subject, for example, hairs on the top of the head, on the armpits, on the pubic area, on the face including eyelash, eyebrow, eyelid, mustache, beard and whisker, on the chest, arms and legs.
• the term "promoting hair growth” in -the present specification and claims covers not only promoting hair growth but also promoting hair germination and thickening hairs.
• the composition of the present invention has the effect of thickening the growing hair in addition to the promotion of hair growth.
• the composition may -be provided as, for example, pharmaceuticals, quasi-drugs (i.e.
• the composition may topically be applied for the purpose of promoting hair growth onto the surface of skin where hair growth is desired, such as scalp, face, beard, head, pubic area, upper lip, eyelash, eyebrow, and eyelid.
• the dose of the prostaglandin compound in the composition of the present invention may vary according to the compound to be used, the type of subject, age, skin area to be applied the composition, progress of baldness or desired effect, administration volume and period for treatment.
• the formulation containing 0.0000001% - 10%, preferably 0.00001% - 5%, more preferably 0.0001%.-- 1% and especially• 0.001-0.1% of the active ingredient can be applied 1-6 times, preferably 1-4 times per day.
• the dosage form of the composition of the present invention can be any of known topically applicable forms. For example, but- not limited thereto, lotion, tonic, emulsion, external ' drug creams such as liniments and milky lotions, external semi-solid preparations such as ointments, paste, jelly and sprays.
• the composition may also be formulated as hair shampoos or hair rinses.
• composition of the present invention may further contain physiologically acceptable additives.
• Said additives may include the ingredients used with the present compounds such as excipient, diluent, filler, resolvent, lubricant, adjuvant, binder, disintegrator, emulsifier, dispersing agent, suspending agent, thickener, tonicity agent, buffering agent, soothing agent, preservative, antioxidant, corrigent, flavor, colorant, a functional material such as cyclodextrin and biodegradable polymer, stabilizer. They may be further dissolved in an appropriate solvent such as fatty acid or its mono, di or triglyceride.
• the additives are well known to the art and may be selected from those described in general reference books of pharmaceutics or cosmetics.
• composition of the present invention may further contain other ingredients as far as they do not contradict the purpose of the present invention.
• the composition may be prepared in a conventional manner for manufacturing the desired formulations by adding the prostaglandin compound defined as above.
• the further details of the present invention will follow with reference to test examples, which, however, are not intended to limit the present invention. Synthesis example 1
• the reaction mixture was stirred at 45°C for 17 hours, then cooled to room temperature, and evaporated. To the residue, water (100 ml) was added. The mixture was extracted with ethyl acetate (100 ml x 2) . The organic layer was washed with 0. lN-hydrochloric acid, saturated aqueous sodium bicarbonate (100 ml) and saturated aqueous sodium chloride (100 ml) . The extract was dried over anhydrous magnesium sulfate and evaporated.
• mice without visible scratches were selected and used in this study.
• Each group consisted of 3 animals. After group assignment, the groups were housed separately in aluminum cages (3 animals/cage, 180 mm W x 300 mm D x 130 mm H; Nippon Cage, Ltd. , Japan) .
• Each test compound was dissolved in 70% (w/w) aqueous ethanol.
• Each dose formulation of test compound was evenly applied topically once daily (100 ⁇ L per mouse) to the clipped dorsal skin area (approximately 2 4 cm) , except for Saturday and Sunday, for 30 days.
• the control group received an equal amount of the vehicle in the same manner. Macroscopic observations of the hair growth were performed 14, 16, 18, 21, 23, 25, 28 and 30 days after the start of the treatment. Hair growth was scored according to the scale below: ⁇ - no hair growth observed ⁇ hair growth ⁇ 10% of the clipped area + hair growth 10 - 40% of the clipped area ++ hair growth 40 - 80% of the clipped area +++ hair growth ⁇ 80% of the clipped area
• test compound compound E
• the formulation of test compound was evenly applied topically once daily (100 ⁇ L per mouse) to the clipped dorsal skin area (approximately 2 x 4 cm) , except for Saturday and Sunday, for 23 days.
• the control group received an equal amount of the vehicle in the same manner. Macroscopic observations of the hair growth were performed 14, 16, 18, 21 and 23 days after the start of the treatment. Hair growth was scored according to the scale shown as above. Results are shown in Table 2. In the 0.1% compound E-treated group, hair growth was observed on 3 out of 3 animals .

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Organic Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Birds (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Emergency Medicine (AREA)
• Dermatology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Cosmetics (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Priority Applications (13)

Applications Claiming Priority (2)

Related Child Applications (2)

Publications (1)

Family

ID=34135320

Family Applications (1)

Country Status (15)

Cited By (6)

Families Citing this family (4)

Citations (6)

Family Cites Families (57)

• 2004
  • 2004-08-11 TW TW099126213A patent/TWI495471B/zh not_active IP Right Cessation
  • 2004-08-11 TW TW093124177A patent/TWI348386B/zh not_active IP Right Cessation
  • 2004-08-12 CA CA2534645A patent/CA2534645C/en not_active Expired - Fee Related
  • 2004-08-12 EP EP04771825A patent/EP1673058B1/en not_active Revoked
  • 2004-08-12 SI SI200431752T patent/SI1673058T1/sl unknown
  • 2004-08-12 PT PT04771825T patent/PT1673058E/pt unknown
  • 2004-08-12 ES ES04771825T patent/ES2369892T3/es not_active Expired - Lifetime
  • 2004-08-12 KR KR1020117017023A patent/KR101166738B1/ko not_active Expired - Fee Related
  • 2004-08-12 PL PL04771825T patent/PL1673058T3/pl unknown
  • 2004-08-12 CN CN2004800298049A patent/CN1867310B/zh not_active Expired - Fee Related
  • 2004-08-12 KR KR1020117031353A patent/KR20120008080A/ko not_active Ceased
  • 2004-08-12 EP EP10008142A patent/EP2243771A3/en not_active Withdrawn
  • 2004-08-12 US US10/567,462 patent/US8686035B2/en not_active Expired - Fee Related
  • 2004-08-12 JP JP2006519266A patent/JP4642021B2/ja not_active Expired - Fee Related
  • 2004-08-12 DK DK04771825.9T patent/DK1673058T3/da active
  • 2004-08-12 WO PCT/JP2004/011864 patent/WO2005013928A1/en not_active Ceased
  • 2004-08-12 KR KR1020067002643A patent/KR101137750B1/ko not_active Expired - Fee Related
  • 2004-08-12 AT AT04771825T patent/ATE526008T1/de active
• 2010
  • 2010-10-06 JP JP2010226217A patent/JP5318837B2/ja not_active Expired - Fee Related
• 2011
  • 2011-11-21 CY CY20111101121T patent/CY1112076T1/el unknown
• 2014
  • 2014-02-07 US US14/175,356 patent/US20140171496A1/en not_active Abandoned

Patent Citations (6)

Also Published As

Similar Documents

Legal Events