JP2009084298A - Hair-growing and hair-restoring agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a hair-growing and hair-restoring agent, which is further improved in the hair-growing and hair-restoring effect without adverse effects such as itching, etc., although a conventional hair growth-prompting composition containing a prostaglandin compound having two hetero atoms at the fifteenth position as an active ingredient and a hair-growing and hair restoring agent containing a 15-keto-prostaglandin compound as an active ingredient have been disclosed. <P>SOLUTION: This hair-growing and hair-restoring agent comprises a prostaglandin compound having two hetero atoms at the fifteenth position being included in a liposome, as an active ingredient. Another hair-growing and hair-restoring agent comprises a 15-keto prostaglandin compound being included in a liposome as an active ingredient. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a hair nourishing and hair restorer.

Patent Document 1 discloses a hair growth promoting composition containing a prostaglandin compound having two heteroatoms at the 15-position as an active ingredient.
Patent Document 2 discloses a hair growth / hair growth agent containing a 15-keto-prostaglandin compound as an active ingredient.

Special table 2007-518685 gazette JP-A-10-287532

  An object of the present invention is to provide a hair nourishing and hair restoring agent that further enhances the hair nourishing and hair restoring effect and suppresses side effects such as itching.

The invention described in claim 1 is a hair nourishing / hair-growing agent comprising a prostaglandin compound having two heteroatoms at the 15-position as a liposome and using this as an active ingredient.
The invention according to claim 2 is a hair nourishing / hair-growth agent comprising a 15-keto-prostaglandin compound as a liposome and using this as an active ingredient.

  According to the present invention, it is possible to provide a hair nourishing and hair restoring agent that further enhances the hair nourishing and hair restoring effect and suppresses side effects such as itching.

First, a prostaglandin compound having two heteroatoms at the 15-position will be described.
In addition, when naming a PG compound used in the present specification and claims, the contents described in Patent Document 1 are followed. I will quote below. The prostanoic acid number shown in the following formula (A) is used.

The formula (A) has a basic skeleton of C-20, but the number of carbons is not limited by this in the present invention. That is, in the formula (A), the number of carbon constituting the basic skeleton of the PG compound is 1, with carboxylic acid being 1, 2 to 7 in order toward the 5-membered ring, carbon on the α chain, and 8 to 12 to 5 member. The ring carbons are numbered 13 to 20 on the ω chain, but when the carbon number decreases on the α chain, the numbers are sequentially deleted from the 2nd position. When the carbon number increases on the α chain, it is named as a substituted compound having a corresponding substituent at the 2-position instead of the carboxyl group (C-1). Similarly, when the number of carbons decreases on the ω chain, names are sequentially deleted from the 20th position. When the carbon number increases on the ω chain, the 21st and subsequent carbon atoms are named as substituents. Further, regarding the configuration, unless otherwise specified, the configuration of the basic skeleton (A) is followed.

Further, for example, PGD, PGE, and PGF refer to PG compounds having a hydroxyl group at the 9-position and / or the 11-position, but in the present invention, those having other groups instead of the 9-position and / or the 11-position hydroxyl group may also be used. Include. When naming these compounds, they are named in the form of 9-dehydroxy-9-substituted-PG compounds or 11-dehydroxy-11-substituted-PG compounds. A PG compound having hydrogen instead of a hydroxyl group is simply referred to as 9- or 11-dehydroxy-PG compound.

As described above, the PG compound is named based on the prostanoic acid skeleton, but if the compound has a partial structure similar to that of prostaglandin, the abbreviation “PG” should be used for the sake of brevity. There is. In this case, the PG compound in which the skeleton carbon number of the α chain is extended by two, that is, the PG compound having the skeleton carbon number of 9 in the α chain is the 2-decarboxy-2- (2-carboxyethyl) -PG compound and Naming. Similarly, a PG compound having 11 carbon atoms in the α chain is named 2-decarboxy-2- (4-carboxybutyl) -PG compound. Further, a PG compound in which the skeleton carbon number of the ω chain is extended by 2, that is, a PG compound having a ω chain skeleton carbon number of 10, is named 20-ethyl-PG compound. The naming can be performed based on the IUPAC nomenclature.

Examples of analogs (including substituents) or derivatives are compounds in which the carboxyl group at the terminal of the α chain of the PGs is esterified, compounds in which the α chain is extended, physiologically acceptable salts thereof, 2- A compound in which the carbon bond at the 3-position has a double bond or the carbon bond at the 5-6 position has a triple bond, the 3-position, the 5-position, the 6-position, the 16-position, the 17-position, the 18-position, the 19-position and / or the 20-position Or a compound having a lower alkyl group or a hydroxy (lower) alkyl group in place of the hydroxyl group at the 9th and / or 11th position.

In the present invention, suitable substituents at the 3-position, 17-position, 18-position and / or 19-position include, for example, an alkyl group having 1 to 4 carbon atoms, particularly a methyl group and an ethyl group. Suitable substituents at the 16-position include lower alkyl such as methyl and ethyl, halogen atoms such as hydroxy, chlorine and fluorine, and aryloxy such as trifluoromethylphenoxy. Suitable substituents at the 17-position include lower alkyl such as methyl and ethyl, halogen atoms such as hydroxy, chlorine and fluorine, and aryloxy such as trifluoromethylphenoxy. Suitable substituents at the 20-position include saturated or unsaturated lower alkyl groups such as C1-4 alkyl, lower alkoxy groups such as C1-4 alkoxy, and lower groups such as C1-4 alkoxy-C1-4 alkyl. Including alkoxyalkyl. Suitable substituents at the 5-position include halogen atoms such as chlorine and fluorine. Suitable substituents at the 6-position include oxo groups that form carbonyl groups. The configuration of PGs having a hydroxy group, lower alkyl or hydroxy (lower) alkyl substituent at the 9-position and / or 11-position may be α, β, or a mixture thereof.

Further, the analog or derivative is a compound having a substituent such as an alkoxy group, a cycloalkyl group, a cycloalkyloxy group, a phenoxy group or a phenyl group at the end of the ω chain of a compound having a shorter ω chain than natural PGs. Also good.

A suitable prostaglandin compound group used in the present invention is the same as the compound described in Patent Document 1. I will quote below. That is, a suitable prostaglandin compound is represented by the following formula (I):

Wherein 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; The member ring may have at least one double bond);
A represents —CH ₃ , or —CH ₂ OH, —COCH ₂ OH, —COOH, or a functional derivative thereof;
B is —CH ₂ —CH ₂ —, —CH═CH— or —C≡C—;
Z ₁ and Z ₂ are oxygen, nitrogen or sulfur;
R ₂ and R ₃ are optionally substituted lower alkyl and may be joined together to form a lower alkylene;
R ₁ is a saturated or unsaturated divalent low to intermediate aliphatic hydrocarbon residue which is unsubstituted or substituted with a halogen, alkyl, hydroxy, oxo, aryl or heterocyclic group, and at least one of the aliphatic hydrocarbons The carbon atom may be optionally substituted by oxygen, nitrogen or sulfur; and
Ra is unsubstituted or substituted with a halogen, oxo, hydroxy, lower alkoxy, lower alkanoyloxy, cyclo (lower) alkyl, cyclo (lower) alkyloxy, aryl, aryloxy, heterocyclic group or heterocyclic oxy group Or unsaturated low to intermediate aliphatic hydrocarbon residues; lower alkoxy; lower alkanoyloxy; cyclo (lower) alkyl; cyclo (lower) alkyloxy; aryl; aryloxy; heterocyclic group or heterocyclic oxy group].

A more preferred prostaglandin compound used in the present invention is represented by the formula (II):

[Wherein L and M are hydrogen, hydroxy, halogen, lower alkyl, hydroxy (lower) alkyl, lower alkanoyloxy or oxo, provided that at least one of the groups L and M is a group other than hydrogen. And the 5-membered ring may have at least one double bond);
A represents —CH ₃ or —CH ₂ OH, —COCH ₂ OH, —COOH or a functional derivative thereof;
B is —CH ₂ —CH ₂ —, —CH═CH— or —C≡C—;
Z ₁ and Z ₂ are oxygen, nitrogen or sulfur;
R ₂ and R ₃ are optionally substituted lower alkyl and may be joined together to form a lower alkylene;
X ₁ and X ₂ are hydrogen, lower alkyl or halogen;
R ₁ is a divalent saturated or unsaturated low to intermediate aliphatic hydrocarbon residue which is unsubstituted or substituted with halogen, alkyl, hydroxy, oxo, aryl or heterocycle, and in aliphatic hydrocarbons At least one carbon atom may be optionally substituted by oxygen, nitrogen or sulfur;
R ₄ is a single bond or lower alkylene; and
R ₅ is lower alkyl, lower alkoxy, lower alkanoyloxy, cyclo (lower) alkyl, cyclo (lower) alkyloxy, aryl, aryloxy, heterocyclic or heterocyclic oxy group].

In the above formulas, the term “unsaturated” in the definition of R ₁ and Ra isolates one or more double and / or triple bonds as a bond between the main chain and / or side chain carbon atoms. , Means containing separately or sequentially. In accordance with normal nomenclature, unsaturated bonds between two consecutive positions are indicated by displaying the lower position number, and unsaturated bonds between two non-consecutive positions are indicated by displaying both position numbers.

The term “low to intermediate aliphatic hydrocarbon” means a hydrocarbon group having a straight chain or branched chain having 1 to 14 carbon atoms (however, the side chain preferably has 1 to 3 carbon atoms). Preferably, it is a hydrocarbon group having 1 to 10 carbon atoms, particularly 1 to 8 carbon atoms.

The term “halogen atom” includes fluorine, chlorine, bromine and iodine.

The term “lower” includes groups having 1 to 6 carbon atoms unless otherwise specified.

The term “lower alkyl” means a straight or branched saturated hydrocarbon group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl. including.

The term “lower alkylene” means a linear or branched divalent saturated hydrocarbon group having 1 to 6 carbon atoms, such as methylene, ethylene, propylene, isopropylene, butylene, isobutylene, t-butylene, Contains pentylene and hexylene.

The term “lower alkoxy” means a lower alkyl-O— group wherein lower alkyl is as defined above.

The term “hydroxy (lower) alkyl” means lower alkyl as described above substituted with at least one hydroxy group, for example hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl and 1-methyl-1- Hydroxyethyl is mentioned.

The term “lower alkanoyloxy” means a group represented by the formula RCO—O— (where RCO— is an acyl group formed by oxidation of a lower alkyl group as described above, for example, acetyl).

The term “cyclo (lower) alkyl” means a cyclic group formed by closing a lower alkyl group containing 3 or more carbon atoms as described above, and includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

The term “cyclo (lower) alkyloxy” means a cyclo (lower) alkyl-O— group in which cyclo (lower) alkyl is as defined above.

The term “aryl” includes unsubstituted or substituted aromatic hydrocarbon ring groups, exemplified by (preferably monocyclic) such as phenyl, tolyl, xylyl. Examples of the substituent include a halogen atom and halo (lower) alkyl (wherein the halogen atom and lower alkyl are as defined above).

The term “aryloxy” means a group of the formula ArO—, wherein Ar is aryl as described above.

The term “heterocyclic group” includes optionally substituted carbon atoms and 1 to 4 hetero atoms selected from a nitrogen atom, oxygen atom and sulfur atom, preferably 1 to 3 hetero atoms. 5 to 14 membered, preferably 5 to 10 membered, monocyclic to tricyclic, preferably monocyclic heterocyclic groups are included. Heterocyclic groups include furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, furazanyl, pyranyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl 2-pyrrolinyl group, pyrrolidinyl group, 2-imidazolinyl group, imidazolidinyl group, 2-pyrazolinyl group, pyrazolidinyl group, piperidino group, piperazinyl group, morpholino group, indolyl group, benzothienyl group, quinolyl group, isoquinolyl group, purinyl group, Examples include quinazolinyl group, carbazolyl group, acridinyl group, phenanthridinyl group, benzimidazolyl group, benzimidazolinyl group, benzothiazolyl group, phenothiazinyl group and the like. Examples of the substituent include halogen and a halogen-substituted lower alkyl group (wherein the halogen atom and the lower alkyl group are as defined above).

The term “heterocyclic oxy group” means a group represented by the formula HcO— (where Hc is a heterocyclic group as described above).

The term “functional derivative” of A includes salts (preferably pharmaceutically acceptable salts), ethers, esters and amides.

Suitable "pharmaceutically acceptable salts" include conventional non-toxic salts, such as salts with inorganic bases, such as alkali metal salts (sodium salts, potassium salts, etc.), alkaline earth metal salts (calcium salts, Magnesium salts, etc.), ammonium salts; or salts with organic bases such as amine salts (eg methylamine salts, dimethylamine salts, cyclohexylamine salts, benzylamine salts, piperidine salts, ethylenediamine salts, ethanolamine salts, diethanolamine salts, Ethanolamine salt, tris (hydroxymethylamino) ethane salt, monomethyl-monoethanolamine salt, procaine salt, caffeine salt etc.), basic amino acid salt (eg arginine salt, lysine salt etc.), tetraalkylammonium salt etc. It is done. These salts can be prepared, for example, from the corresponding acids and bases by conventional reactions or by salt exchange.

Examples of ethers include alkyl ethers such as methyl ether, ethyl ether, propyl ether, isopropyl ether, butyl ether, isobutyl ether, t-butyl ether, pentyl ether, 1-cyclopropyl ethyl ether, and other lower alkyl ethers; Intermediate or higher alkyl ethers such as ethylhexyl ether, lauryl ether, cetyl ether; unsaturated ethers such as oleyl ether and linolenyl ether; lower alkenyl ethers such as vinyl ether and allyl ether; lower alkynyl ethers such as ethynyl ether and propynyl ether; hydroxy Hydroxy (lower) alkyl ethers such as ethyl ether and hydroxyisopropyl ether; methoxymethyl ether, 1-methyl Lower alkoxy (lower) alkyl ethers such as xylethyl ether; optionally substituted aryl ethers such as phenyl ether, tosyl ether, t-butylphenyl ether, salicyl ether, 3,4-dimethoxyphenyl ether, benzamidophenyl ether; And aryl (lower) alkyl ethers such as benzyl ether, trityl ether, and benzhydryl ether.

Examples of esters include methyl esters, ethyl esters, propyl esters, isopropyl esters, butyl esters, isobutyl esters, t-butyl esters, pentyl esters, 1-cyclopropylethyl esters and the like lower alkyl esters; vinyl esters, allyl esters, and the like. Alkenyl esters; lower alkynyl esters such as ethynyl esters and propynyl esters; hydroxy (lower) alkyl esters such as hydroxyethyl esters; aliphatic esters such as lower alkoxy (lower) alkyl esters such as methoxymethyl esters and 1-methoxyethyl esters And, for example, phenyl ester, tolyl ester, t-butylphenyl ester, salicyl ester, 3,4-dimethoxyphenyl ester, benzamidophenol Examples include optionally substituted aryl esters such as nyl esters; aryl (lower) alkyl esters such as benzyl esters, trityl esters and benzhydryl esters.

The amide of A is a group represented by the formula —CONR′R ″; in which R ′ and R ″ are hydrogen, lower alkyl, aryl, alkyl- or aryl-sulfonyl, lower alkenyl and lower alkynyl, respectively. For example, lower alkylamides such as methylamide, ethylamide, dimethylamide, and diethylamide; arylamides such as anilide and toluidide; and alkyl- or aryl-sulfonylamides such as methylsulfonylamide, ethylsulfonylamide, and tolylsulfonylamide. It is done.

Preferred examples of L and M include those having a five-membered ring structure referred to as a so-called PGF type in which hydroxy and oxo are included, and M and L are hydroxy.

Preferred A is —COOH, a pharmaceutically acceptable salt, ester or amide thereof.

Preferred B is —CH ₂ —CH ₂ —, which is referred to as a so-called 13,14-dihydrotype.

A preferred example of X ₁ and X ₂ is fluorine, which is called the so-called 16,16-difluoro type.

Preferred R ₁ is a hydrocarbon residue having 1 to 10 carbon atoms, particularly preferably 6 to 10 carbon atoms. At least one carbon atom in the aliphatic hydrocarbon may be substituted with oxygen, nitrogen or sulfur.

Specific examples of R ₁ include, for example:
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -,
_{-CH 2 -CH = CH-CH 2} -CH 2 -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH = CH-,
_{-CH 2 -C≡C-CH 2 -CH 2} -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -O-CH 2 -,
_{-CH 2 -CH = CH-CH 2} -O-CH 2-,
_{-CH2-C≡ C-CH 2 -O} -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -CH 2 -,
_{-CH 2 -CH = CH-CH 2} -CH 2 -CH 2 -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH = CH-,
_{-CH 2 -C≡C-CH 2 -CH 2} -CH 2 -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH (CH 3) -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH (CH 3) -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -CH 2 -CH 2 -,
_{-CH 2 -CH = CH-CH 2} -CH 2 -CH 2 -CH 2 -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -CH = CH-,
_{-CH 2 -C≡C-CH 2 -CH 2} -CH 2 -CH 2 -CH 2 -, and,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -CH (CH 3) -CH 2 -.

Preferred Ra is a hydrocarbon having 1-10 carbon atoms, more preferably 1-8 carbon atoms. Ra may have 1 or 2 side chains having 1 carbon atom.

Preferred Z ₁ and Z ₂ are oxygen.

R ₂ and R ₃ are preferably joined together to form C2 or C3 alkylene.

The arrangement of the ring and the α- and / or ω-chain in the above formulas (I) and (II) may be the same as or different from the arrangement of the natural PGs. However, the present invention also encompasses mixtures of compounds having a natural type configuration and compounds having a non-natural type configuration.

In the present invention, isomers such as individual tautomers, mixtures or optical isomers, mixtures, racemates and other stereoisomers can be used for the same purpose.

In the present invention, a preferred prostaglandin compound is 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF2α isopropyl ester, 13,14-dihydro-15,15-ethylenedioxy-17-phenyl. -18,19,20-trinol-PGF2α isopropyl ester, 13,14-dihydro-15,15-trimethylenedioxy-20-ethyl-PGF2α isopropyl ester, 13,14-dihydro-15,15-dimethoxy-20- Ethyl-PGF2α isopropyl ester and 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF2α ethyl ester. In particular, 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF2α ethyl ester is preferably used.

Next, the 15-keto-plastaglandin compound will be described. The said compound is a well-known compound, and is described in international publication WO2005 / 018646 pamphlet, The preferable range is also the same. I will quote below.
The 15-keto PGs used in the present invention can be any PG derivative having an oxo group instead of a hydroxyl group at the 15-position, and a 15-keto-PG type 1 compound having one double bond at the 13-14 position. , 15-keto-PG type 2 compounds having two double bonds at positions 13-14 and 5-6, three double bonds at positions 5-6, 13-14, and 17-18 And 15-keto-PG type 3 compounds having 13, or 13,14-dihydro-15-keto-PG compounds in which the double bond at positions 13-14 of these compounds is a single bond.
Examples of substituents or derivatives are compounds in which the carboxyl group at the α-chain end of the PG compound is esterified, physiologically acceptable salts, the carbon bond at the 2-3 position is a double bond, or the 5-6 position. Compound having triple bond of carbon bond, compound having substituent at carbon at 3rd, 5th, 6th, 16th, 17th, 18th, 19th and / or 20th position, hydroxyl group at 9 / 11th position Instead of these, a compound having a lower alkyl group or a hydroxy (lower) alkyl group is used.
In the present invention, examples of the substituent bonded to the 3-position, 17-position, 18-position and / or 19-position carbon atom include an alkyl group having 1 to 6 carbon atoms, and particularly a methyl group and an ethyl group. Examples of the substituent bonded to the 16th carbon atom include a lower alkyl group such as a methyl group and an ethyl group, a hydroxyl group or a halogen atom such as chlorine and fluorine, and an aryloxy group such as trifluoromethylphenoxy. Examples of the substituent at the 17th carbon atom include halogen atoms such as chlorine and fluorine. Examples of the substituent bonded to 20 position carbon _{atoms, C 1-4} lower alkyl group, saturated or unsaturated, such as _alkyl, lower alkoxy such as _{C 1-4 alkoxy, C 1-4} alkoxy -C ₁ Including lower alkoxyalkyl such as _-4 alkyl. The substituent at the 5-position carbon atom includes a halogen atom such as chlorine and fluorine. The substituent at the 6-position carbon atom includes an oxo group forming a carbonyl group. When the 9th and 11th carbon atoms have a hydroxy group, a lower alkyl or a lower (hydroxy) alkyl substituent, the configuration of these groups may be α, β or a mixture thereof.
Further, the above derivative may have a substituent such as an alkoxy group, a cyclohexyl group, a cyclohexyloxy group, a phenoxy group, or a phenyl group at the terminal of the ω chain of a compound having a shorter ω chain than natural PGs.
Particularly preferred compounds include a 13,14-dihydro-15 keto-PG compound in which the carbon bond at the 13-14 position becomes a single bond, and a compound having a lower alkyl (especially ethyl) group at the 20 position carbon (15-keto). -20-lower alkyl (especially ethyl) -PG compound) and compounds having a hydroxyl group at the 9- and 11-position carbons of a 5-membered ring (15-keto-PGF compound).
Preferred compounds for use in the present invention are those represented by the following formula (I):

Wherein L, M and N are hydrogen, hydroxy, halogen, lower alkyl, hydroxy (lower) alkyl, lower alkanoyloxy or oxo (provided that at least one of the L and M groups is other than hydrogen) A 5-membered ring may have at least one double bond);
A represents —CH ₃ , —CH ₂ OH, —COCH ₂ OH, —COOH, or a functional derivative thereof;
Is _{B, -CH 2 -CH 2 -,} - CH = CH -, - C≡C -, - CH 2 -CH 2 -CH 2 -, - CH = CH-CH 2 -, - CH 2 -CH = CH -, -C≡C-CH ₂ -or -CH ₂ -C≡C-;
Z is

(R ₄ and R ₅ are hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or hydroxy (lower) alkyl, provided that R ₄ and R ₅ are not simultaneously hydroxy and lower alkoxy);
R ₁ is a divalent saturated or unsaturated, low to intermediate aliphatic hydrocarbon residue which is unsubstituted or substituted with a halogen, alkyl, hydroxy, oxo, aryl or heterocyclic ring (at least one of the aliphatic hydrocarbons). One carbon atom may optionally be replaced by oxygen, nitrogen or sulfur); and
Ra is unsubstituted or substituted with halogen, oxo, hydroxy, lower alkoxy, lower alkanoyloxy, cyclo (lower) alkyl, cyclo (lower) alkyloxy, aryl, aryloxy, heterocyclic or heterocyclic oxy, saturated or An unsaturated low to intermediate aliphatic hydrocarbon residue (at least one carbon atom of the aliphatic hydrocarbon may optionally be replaced by oxygen, nitrogen or sulfur); a cyclo (lower) alkyl group; a cyclo (lower An alkyloxy group; an aryl group; an aryloxy group; a heterocyclic group; a heterocyclic oxy group].
Among the above compounds, a particularly preferred group of compounds are those represented by formula (II):

[Wherein L and M are hydrogen, hydroxy, halogen, lower alkyl, hydroxy (lower) alkyl, lower alkanoyloxy or oxo, provided that at least one of the groups of L and M is a group other than hydrogen. And the 5-membered ring may have at least one double bond);
A represents —CH ₃ , —CH ₂ OH, —COCH ₂ OH, —COOH, or a functional derivative thereof;
Is _{B, -CH 2 -CH 2 -,} - CH = CH -, - C≡C -, - CH 2 -CH 2 -CH 2 -, - CH = CH-CH 2 -, - CH 2 -CH = CH -, -C≡C-CH ₂ -or -CH ₂ -C≡C-;
Z is

(R ₄ and R ₅ are hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or hydroxy (lower) alkyl, provided that R ₄ and R ₅ are not simultaneously hydroxy and lower alkoxy);
X ₁ and X ₂ are hydrogen, lower alkyl or halogen;
R ₁ is a divalent saturated or unsaturated, low to intermediate aliphatic hydrocarbon residue which is unsubstituted or substituted with a halogen, alkyl, hydroxy, oxo, aryl or heterocyclic ring (at least one of the aliphatic hydrocarbons). One carbon atom may optionally be replaced by oxygen, nitrogen or sulfur);
R ₂ is a single bond or lower alkylene (at least one carbon atom of the lower alkylene may be optionally replaced with oxygen, nitrogen or sulfur); and
R ₃ is cyclo (lower) alkyl, cyclo (lower) alkyloxy, aryl, aryloxy, heterocyclic or heterocyclic oxy].
In the above formula, the term “unsaturated” in R ₁ and Ra means that at least one or more double bonds and / or triple bonds are isolated as a bond between main chain and / or side chain carbon atoms. , Means containing separately or sequentially. In accordance with normal nomenclature, unsaturation between two consecutive positions is indicated by displaying the lower position number, and unsaturation between two non-consecutive positions is indicated by displaying both position numbers.
The term “low to intermediate aliphatic hydrocarbon” means a hydrocarbon having a straight or branched chain having 1 to 14 carbon atoms (however, the side chain is preferably one having 1 to 3 carbon atoms), preferably Is a hydrocarbon having 1 to 10 carbon atoms, particularly 6 to 10 carbon atoms in the case of R ₁ , and a hydrocarbon having 1 to 10 carbon atoms, particularly 1 to 8 carbon atoms, in the case of Ra.
The term “halogen” includes fluorine, chlorine, bromine and iodine.
The term “lower” includes groups having 1 to 6 carbon atoms unless otherwise specified.
The term “lower alkyl” includes straight or branched chain saturated hydrocarbon groups of 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl.
The term “lower alkoxy” means lower alkyl-O—, wherein lower alkyl is as defined above.
The term “hydroxy (lower) alkyl” means lower alkyl as described above substituted with at least one hydroxy group, for example hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl and 1-methyl-1- Hydroxyethyl.
The term “lower alkanoyloxy” means a group represented by the formula RCO—O—, wherein RCO— is an acyl formed by oxidation of a lower alkyl as described above, such as acetyl.
The term “cyclo (lower) alkyl” is a cyclic group formed by ring closure of a lower alkyl group containing 3 or more carbon atoms, and includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
The term “cyclo (lower) alkyloxy” means cyclo (lower) alkyl-O—, wherein cyclo (lower) alkyl is as defined above.
The term “aryl” includes an aromatic hydrocarbon ring group which may be unsubstituted or substituted, and is preferably monocyclic, for example, phenyl, tolyl, xylyl. Substituents include halogen and halogen-substituted lower alkyl groups (wherein halogen and lower alkyl groups are as defined above).
The term “aryloxy” means a group represented by the formula ArO— (wherein Ar is an aryl group as described above).
As the “heterocycle”, 1 to 4 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in addition to the carbon atom and carbon atom which may have a substituent, preferably Is a monocyclic to tricyclic, preferably monocyclic heterocyclic group having 1 to 3, 5 to 14 members, preferably 5 to 10 members. Heterocyclic groups include furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, furazanyl, pyranyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl 2-pyrrolinyl group, pyrrolidinyl group, 2-imidazolinyl group, imidazolidinyl group, 2-pyrazolinyl group, pyrazolidinyl group, piperidino group, piperazinyl group, morpholino group, indolyl group, benzothienyl group, quinolyl group, isoquinolyl group, purinyl group, Examples include quinazolinyl group, carbazolyl group, acridinyl group, phenanthridinyl group, benzimidazolyl group, benzimidazolinyl group, benzothiazolyl group, phenothiazinyl group and the like. Examples of the substituent include a halogen and a halogen-substituted lower alkyl group (wherein the halogen and the lower alkyl group are as defined above).
The term “heterocyclicoxy” means a group represented by the formula HcO— (wherein Hc is a heterocyclic group as described above).
The term “functional derivative” of A includes salts (preferably pharmaceutically acceptable salts), ethers, esters and amides.
Suitable "pharmaceutically acceptable salts" include conventional non-toxic salts, such as salts with inorganic bases, such as alkali metal salts (sodium salts, potassium salts, etc.), alkaline earth metal salts (calcium salts, Magnesium salts, etc.), ammonium salts, salts with organic bases such as amine salts (eg methylamine salts, dimethylamine salts, cyclohexylamine salts, benzylamine salts, piperidine salts, ethylenediamine salts, ethanolamine salts, diethanolamine salts, triethanol) Amine salts, tris (hydroxymethylamino) ethane salts, monomethyl-monoethanolamine salts, procaine salts, caffeine salts, etc.), basic amino acid salts (for example, arginine salts, lysine salts, etc.), tetraalkylammonium salts, etc. . These salts can be prepared, for example, from the corresponding acids and bases by conventional reactions or by salt exchange.
Examples of ethers include alkyl ethers such as methyl ether, ethyl ether, propyl ether, isopropyl ether, butyl ether, isobutyl ether, t-butyl ether, pentyl ether, 1-cyclopropylethyl ether, and other lower alkyl ethers, octyl ether, di- Intermediate or higher alkyl ethers such as ethylhexyl ether, lauryl ether, cetyl ether, unsaturated ethers such as oleyl ether and linolenyl ether, lower alkenyl ethers such as vinyl ether and allyl ether, lower alkynyl ethers such as ethynyl ether and propynyl ether, hydroxy Hydroxy (lower) alkyl ethers such as ethyl ether, hydroxyisopropyl ether, methoxymethyl ether, 1 Lower alkoxy (lower) alkyl ethers such as methoxyethyl ether and optionally substituted aryl ethers such as phenyl ether, tosyl ether, t-butylphenyl ether, salicyl ether, 3,4-dimethoxyphenyl ether, benzamide phenyl ether, etc. , Aryl (lower) alkyl ethers such as benzyl ether, trityl ether, and benzhydryl ether.
Esters include methyl esters, ethyl esters, propyl esters, isopropyl esters, butyl esters, isobutyl esters, t-butyl esters, pentyl esters, lower alkyl esters such as 1-cyclopropylethyl ester, lower esters such as vinyl esters and allyl esters. Aliphatics such as lower alkynyl esters such as alkenyl esters, ethynyl esters and propynyl esters, hydroxy (lower) alkyl esters such as hydroxyethyl esters, lower alkoxy (lower) alkyl esters such as methoxymethyl esters and 1-methoxyethyl esters Esters and eg phenyl esters, tolyl esters, t-butylphenyl esters, salicyl esters, 3,4-dimethoxyphenyl esters, benzamides Optionally substituted aryl esters such Eniruesuteru, benzyl ester, trityl ester, aryl (lower) alkyl esters such as benzhydryl ester.
The amide of A means a group represented by the formula —CONR′R ″. Here, R ′ and R ″ are a hydrogen atom, lower alkyl, aryl, alkyl- or aryl-sulfonyl, lower alkenyl and lower, respectively. Alkynyl, for example, lower alkylamides such as methylamide, ethylamide, dimethylamide, diethylamide, arylamides such as anilide and toluizide, alkyl- or aryl-sulfonylamides such as methylsulfonylamide, ethylsulfonylamide, and tolylsulfonylamide Is mentioned.
A preferred example of L and M is hydroxy, which has a five-membered ring structure referred to as a so-called PGF type.
Preferred examples of A are -COOH, pharmaceutically acceptable salts, esters, amides thereof.
A preferred example of B is —CH ₂ —CH ₂ —, which has a structure called a so-called 13,14-dihydrotype.
Preferred X ₁ and X ₂ include hydrogen and halogen, preferably both are hydrogen or at least one is halogen. A compound in which both X ₁ and X ₂ are halogen, particularly fluorine, has a structure called a so-called 16,16-difluoro type, and this is also preferable.
Preferred R ₁ is a hydrocarbon having 1 to 10 carbon atoms, particularly preferably a hydrocarbon having 6 to 10 carbon atoms. In addition, at least one carbon atom in the aliphatic hydrocarbon may optionally be replaced with oxygen, nitrogen or sulfur.
Specific examples of R ₁ include the following.
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -,
_{-CH 2 -CH = CH-CH 2} -CH 2 -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH = CH-,
_{-CH 2 -C≡C-CH 2 -CH 2} -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH (CH 3) -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -O-CH 2 -,
_{-CH 2 -CH = CH-CH 2} -O-CH 2-,
_{-CH2-C≡ C-CH 2 -O} -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -CH 2 -,
_{-CH 2 -CH = CH-CH 2} -CH 2 -CH 2 -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH = CH-,
_{-CH 2 -C≡C-CH 2 -CH 2} -CH 2 -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH (CH 3) -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -CH 2 -CH 2 -,
_{-CH 2 -CH = CH-CH 2} -CH 2 -CH 2 -CH 2 -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -CH = CH-,
_{-CH 2 -C≡C-CH 2 -CH 2} -CH 2 -CH 2 -CH 2 -,
_{-CH 2 -CH 2 -CH 2 -CH 2} -CH 2 -CH 2 -CH (CH 3) -CH 2 -,
Such.
Preferred Ra is a hydrocarbon having 1 to 10 carbon atoms, preferably 1 to 8 carbon atoms, the terminal of which is substituted with an aryl group or an aryloxy group. Here, at least one carbon atom may optionally be replaced by oxygen, nitrogen or sulfur.
In the above formulas (I) and (II), the arrangement of the ring, α and / or ω chain may be the same as or different from the arrangement of natural PGs. However, the present invention also encompasses mixtures of compounds having a natural configuration and compounds having a non-natural configuration.
Examples of typical compounds of the present invention are 13,14-dihydro-15-keto-20-ethyl-PGF compounds or 13,14-dihydro-15-keto-17-phenyl-18,19,20-trinol- Prostaglandin F compound and derivatives or analogs thereof, or 13,14-dihydro-17-phenyl-18,19,20-trinol-PGF2α isopropyl ester, 16- (3-trifluoromethylphenoxy) -17,18 , 19,20-trinol-PGF2α isopropyl ester or 17-phenyl-18,19,20-trinol-PGF2αN-ethylamide.
In the present invention, when the carbon bond at the 13th and 14th positions of the PG compound is a single bond and the 15th position is keto (= O), the keto- is formed by forming a hemiacetal between the hydroxy at the 11th position and the oxo at the 15th position. May cause hemiacetal equilibrium.
For example, when both X ₁ and X ₂ are halogen, particularly fluorine, it has been confirmed that a bicyclic compound exists as a tautomer.
When such a tautomer exists, the abundance ratio of both isomers varies depending on the structure of the other moiety or the type of substituent, and in some cases, one isomer may be overwhelmingly present. The PG compound used in the present invention includes both of them.
Furthermore, the 15-keto-PG compounds used in the present invention include bicyclic compounds and analogs or derivatives thereof. The bicyclic compound is represented by the following formula (III).

[Wherein A represents —CH ₂ OH, —COCH ₂ OH, —COOH or a functional derivative thereof;
X ₁ ′ and X2 ′ are hydrogen, lower alkyl, or halogen;
Y is

R4 ′ and R5 ′ are hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or hydroxy (lower) alkyl, and R4 ′ and R5 ′ are not simultaneously hydroxy and lower alkoxy.
R ₁ is a divalent saturated or unsaturated low to intermediate aliphatic hydrocarbon residue which is unsubstituted or substituted with halogen, alkyl, hydroxy, oxo, aryl or heterocyclic ring, and at least in the aliphatic hydrocarbon One carbon atom may optionally be replaced by oxygen, nitrogen or sulfur;
Ra ′ is saturated, unsubstituted or substituted with halogen, oxo, hydroxy, lower alkoxy, lower alkanoyloxy, cyclo (lower) alkyl, cyclo (lower) alkyloxy, aryl, aryloxy, heterocycle or heterocycleoxy Or an unsaturated low to intermediate aliphatic hydrocarbon residue (at least one carbon atom of the aliphatic hydrocarbon may optionally be replaced by oxygen, nitrogen or sulfur); a cyclo (lower) alkyl group; Lower) alkyloxy group; aryl group; aryloxy group; heterocyclic group; heterocyclic oxy group;
R ₃ ′ is hydrogen, lower alkyl, cyclo (lower) alkyl, aryl or heterocyclic group].
Furthermore, the compounds used in the present invention may be represented by keto structural formulas or nomenclature, regardless of the presence or absence of isomers, but this is for convenience and attempts to exclude hemiacetal type compounds. Not what you want.
In the present invention, isomers such as individual tautomers, mixtures or optical isomers, mixtures, racemates and other stereoisomers can be used for the same purpose.
Some of the compounds used in the present invention are disclosed in U.S. Pat. No. 5,073,569, U.S. Pat. No. 5,166,174, U.S. Pat. No. 5,221,763, U.S. Pat. No. 5,212,324, U.S. Pat. Can be produced by the method described in the above).

In the present invention, the liposome formation can be carried out by any known means and is not particularly limited.
For example, constitutive components include phospholipids, PG compounds of the present invention and water. Phospholipids include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, lysophosphatidylcholine, sphingomyelin, egg yolk lecithin, soy lecithin, synthetic phospholipids such as dioleoylphosphatidylcholine, and unsaturated phospholipids. Examples thereof include hydrogenated phospholipids whose carbon chain is saturated with hydrogen, or other phospholipids extracted from microorganisms such as Escherichia coli. These phospholipids can be used singly or in combination of two or more. Among these, one or more selected from hydrogenated egg yolk phospholipid, hydrogenated soybean phospholipid, hydrogenated phosphatidylcholine, and hydrogenated phosphatidylserine are preferable.
In preparing the liposomes, surfactants, preservatives, oils, colorants, water-soluble polymers, acids, salts and the like may be added as necessary.
The particle size of the obtained liposome can be adjusted using an extruder, a high-pressure emulsifier, ultrasonic waves, and the like, and is, for example, 1 nm to 1000 nm, preferably 5 nm to 500 nm, and more preferably 10 nm to 200 nm.

The amount of the prostaglandin compound in the hair restoration / hair growth agent of the present invention is effective to provide a sufficient hair restoration / hair growth effect and side effect prevention effect, and may be an amount that does not cause difficulty in production of the product. . The amount can be 0.0001-10.0 wt% (dry weight) per total weight of the hair nourishing and hair restorer, preferably 0.001-5.0 wt%.

In the present invention, it is also a preferred form to use a menthol derivative together. The menthol derivative may be any menthol used in cosmetics or pharmaceuticals, and examples thereof include l-menthol and dl-menthol. Menthol derivatives are commercially available or can be obtained by extraction from Mentha herbs, such as peppermint. The menthol derivatives may be used alone or in combination.

The amount of the menthol derivative in the hair nourishing / hair-growing agent of the present invention can be an amount effective to provide an anti-inflammatory, anti-rough skin, anti-dandruff, anti-itchiness, hair growth promoting and / or hair loss preventing effect. Furthermore, the upper limit of the amount should be determined so that the hair nourishing and hair restorer does not provide an unpleasant sensation of irritation and does not pose difficulties in the manufacture of the product.

The amount of the menthol derivative in the hair nourishing and hair restoring agent of the present invention may be 0.001 to 5.0 wt%, preferably 0.01 to 3.0 wt%, based on the total amount of the hair nourishing and hair restoring agent.

In the present invention, it is also a preferred form to use a thickening compound in combination. A thickening compound means a high molecular weight material that dissolves or disperses in an aqueous medium to produce a viscosity. By blending the thickening compound with the PG compound, the sustainability of the action and effect of the PG compound is increased, and a more enhanced action and effect is expressed. Preferable thickening compounds include acrylic acid polymers, polyols, cellulose polymers, polysaccharides and polylactams. Specific examples of thickening compounds that can be used include carbomers (trademarks carbopol 941, 934, 940, 941, 971, 974, 980, 981, etc.), polycarbophil (trademark Noveon ( novelon) Acrylic polymers such as AA-1, CA-1, CA-2) (also known generically as carboxyvinyl polymer); polyols such as polyvinyl alcohol, glycerin, polyethylene glycol; methylcellulose , Cellulose polymers such as methylethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose; carrageenan, gellan gum, xanthan gum, loin Polysaccharides such as bean gum; and polyvinyl polylactam such as pyrrolidone (hereinafter, simply referred to as thickening compound) and the like. In particular, cellulose polymers and polysaccharides are preferably used.
Two or more kinds of these thickening compounds may be used in appropriate combination depending on necessity or purpose. If necessary, the thickening compound used in the present invention may be used in combination with other thickening compounds.
The concentration of the thickening compound varies depending on the concentration of the PG compound, the type of the thickening compound used, the molecular weight, and the like, but is usually about 0.001 to 30 w / v%, preferably 0 with respect to the entire hair nourishing / hair restoration agent. A composition in which a desired effect can be expected at about 0.01 to 10 w / v% can be obtained.

The hair nourishing / hair-growth agent of the present invention may further contain an active ingredient usually added to conventional scalp and / or hair treatment compositions as long as the object of the present invention is not impaired.

The composition of the present invention may be applied or sprayed topically on the scalp or hair. The combination of ingredients effectively absorbs the active ingredient transdermally.

The dose of the hair nourishing / hair restoring agent of the present invention can be determined according to the age and sex of the subject. In general, for adult males, the hair nourishing and hair restorer is applied in an amount of a prostaglandin compound of 0.0001-100 mg / day / kg body weight, preferably 0.001-10 mg / day / kg body weight. The amount may be given in divided doses 2-4 times a day.

The method for synthesizing the active ingredient of the hair nourishing / hair-growth agent of the present invention is described in the prior art including Patent Document 1 as described above, and in the present invention, it is possible to synthesize by adopting the techniques described therein. it can.

Hereinafter, the present invention will be further described by examples.
The following compounds (active ingredients) were synthesized according to the synthesis method described in Patent Document 1 or International Publication WO2005 / 018646.
Compound A: 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF2α isopropyl ester
Compound B: 13,14-dihydro-15,15-ethylenedioxy-17-phenyl-18,19,20-trinol-PGF2α isopropyl ester compound C: 13,14-dihydro-15,15-trimethylenedioxy- 20-ethyl-PGF2α isopropyl ester compound D: 13,14-dihydro-15,15-dimethoxy-20-ethyl-PGF2α isopropyl ester compound E: 13,14-dihydro-15,15-ethylenedioxy-20-ethyl- PGF2α ethyl ester
Compound F: 13,14-dihydro-15-keto-20-ethyl-PGF2α isopropyl ester compound G: 13,14-dihydro-15-keto-18-phenyl-19,20-dinol-PGF2α-isopropyl ester compound H: 13,14-dihydro-15-keto-17-phenoxy-18,19,20-trinol-PGF2α-isopropyl ester

  According to a conventional method, each component shown in Table 1 below was stirred using a homogenizer, and a PG compound having a particle size of about 200 nm was made into a liposome.

According to the experimental procedure described in Japanese Patent No. 4041451, the effect of the active ingredient of the present invention was verified.
(1) Mice test C3H mice (8 weeks old, male, average body weight 35 g) dorsal skin (2 cm × 4 cm) were cut with an electric clipper and shaver, and the samples of Examples and Comparative Examples were applied to the skin of the test site from the next day. Twice morning and evening, 0.2 mL per animal was applied continuously for 2 weeks. A group of 10 animals was used for one sample. On the 22nd day from the start of application, the skin of the test area of each sample was photographed with a video camera, and the areas of the hair cutting part and the hair growth part were measured with an image analyzer. The determination of the hair nourishing effect was carried out by calculating the hair growth rate (%) shown below, and comparing the average hair growth rate of each group of the examples or comparative examples.
Hair growth rate (%) = (Area of hair growth part) / (Area of hair cutting part) × 100

(2) Human test At 10 cm above the ears of 10 male pattern baldness patients, their hair was shaved into a circular shape with a diameter of 5 mm at two left and right sides, and each sample of the examples and comparative examples was left About 3 mL was applied to the entire hair every day in the morning and evening, and the right and left sides were compared without applying anything on the right side. In the determination of the effect of the hair growth rate, the hair growth rate was evaluated with the value obtained by the following formula after removing 20 test part hairs at the left and right shaved sites 1 month after the start of the test.
Hair growth rate = (average length of 20 left hairs) ÷ (average length of 20 right hairs)

  In addition, the hair growth effect, the itch prevention effect, the hair loss effect, and the anti-dandruff effect were determined for each item 3 months after the start of the test, compared to the test site where nothing was applied on the right side. It was shown by the number of respondents who responded that they became bristle or increased their vellus hair, “doesn't feel itchy much”, “has lost hair loss”, and “had less dandruff”.

Examples 1-8 and Comparative Examples 1-2
A hair nourishing and hair restorer with the formulation shown in Table 2 was prepared according to a conventional method, and the above tests were conducted for evaluation. In addition, it formulated so that the application amount of the PG compound of this invention might become the ratio of the said Table 1. The results are also shown in Table 2. In addition, Comparative Examples 1-2 is an example using the PG compound which does not perform liposome formation.

It should be noted that no abnormalities were observed in the skin condition even during and after the long-term use of the hair nourishing / hair-growing agent of the present invention. When the PG compound of the present invention is made into a liposome and when the other PG compound not included in the scope of the present invention is made into a liposome, the above PG compound of the present invention is made into a liposome However, as compared with the latter case, it exhibited a significant improvement effect on the hair-restoring effect and had fewer side effects such as itching.

Example 9 (Tonic)
Compounding amount (%)
(1) 95% ethanol 90.0
(2) Active ingredient of the present invention 0.5
(3) Benzyl nicotinate 0.05
(4) Acetic acid α-DL-tocopherol 0.5
(5) Propylene glycol 1.0
(6) Polyethylene glycol 200 1.0
(7) Fragrance 0.1
(8) Appropriate amount of dye (9) Balance of purified water

Example 10 (Lotion)
Compounding amount (%)
(1) 95% ethanol 80.0
(2) Active ingredient of the present invention 0.2
(3) Nicotinamide 0.5
(4) Cephalanthin 0.01
(5) Dipropylene glycol 2.0
(6) Disodium phosphate 0.08
(7) Monopotassium phosphate 0.02
(8) L-menthol 0.3
(9) Fragrance 0.05
(10) Purified water balance

Claims (2)

  A hair nourishing and hair restorer comprising a prostaglandin compound having two heteroatoms at position 15 as a liposome, which is used as an active ingredient.   A hair nourishing and hair restorer comprising 15-keto-prostaglandin compound as a liposome and using this as an active ingredient.