Composition for preventing or treating male pattern hair loss by adsorption and / or removal of dihydrotestosterone, and uses thereof

Abstract

The present invention relates to a composition for preventing or treating male pattern hair loss by adsorption and / or removal of dihydrotestosterone (DHT), and uses thereof, wherein the composition comprises a metal-organic framework, which penetrates hair follicles and, by adsorbing and / or removing DHT, can exhibit preventive or therapeutic effects against the progression of hair loss. In addition, when the composition is applied to the scalp as a hair serum or a hair cream comprising the metal-organic framework, the metal-organic framework penetrates hair follicles and can continuously adsorb / remove DHT that is continuously released in the body, and the metal-organic framework that has adsorbed and / or removed DHT can be discharged to the outside as the hair grows.

Description

Composition for the prevention or treatment of male pattern baldness by adsorption and / or removal of dihydrotestosterone and the use thereof

[0001] The present invention relates to a composition for the prevention or treatment of male pattern baldness by the adsorption and / or removal of dihydrotestosterone and the use thereof.

[0002] The domestic hair loss population amounts to approximately 10 million people, and the hair loss management and treatment market is worth about 4 trillion won, which is expanding rapidly every year. Although hair loss was once considered the exclusive property of some middle-aged men, it has recently become a 'national disease' affecting people of all ages and genders. Consequently, hair loss is now regarded as a disease requiring active prevention and treatment.

[0003] According to an analysis of medical records for alopecia over a five-year period (2009–2013) by the Health Insurance Review and Assessment Service, patients in their 20s and 30s accounted for 43.9%, nearly half of all alopecia patients. Hair loss shampoos, which had previously been classified as quasi-drugs, faced consumer complaints due to exaggerated advertising and could be mistaken for pharmaceutical treatments or hair growth effects; as a result, they were reclassified as functional cosmetics starting May 30, 2017.

[0004] Furthermore, as oral hair loss treatments require medical consultation and prescription and raise concerns regarding side effects, there is a demand for the development of topical or shampoo-type products that demonstrate equivalent efficacy. The domestic and international markets for hair and hair loss products, as well as functional cosmetics, are growing explosively, and sales of anti-hair loss shampoos in China, in particular, are showing a rapid upward trend.

[0005] Hair loss occurs when the hair formation process in the hair follicle is disrupted by certain factors, thereby preventing the proliferation, differentiation, and growth of hair follicle cells or causing them to die, which inhibits hair production and causes symptoms of hair loss. Testosterone, which acts as a genetic predisposition in this process, is converted into dihydrotestosterone (hereinafter referred to as 'DHT') by 5α-reductase. This DHT acts on the hair follicle to miniaturize it and causes hair loss by shortening the growth phase and lengthening the resting phase of the hair cycle.

[0006] Due to the nature of hair loss treatment, where improvement can only be seen by combining consistent care rather than short-term treatment starting with a hospital visit, home care products are essential.

[0007] However, given that it is unclear whether conventional anti-hair loss shampoos are actually effective, and that people are reluctant to use oral hair loss treatments due to the inconvenience of long-term continuous use and side effects, there is a need to develop products that can demonstrate preventive or therapeutic effects for male pattern baldness through home care.

[0008] [Doctoral Literature]

[0009] [Patent Literature]

[0010] KR 10-2023-0159038 A1

[0011] The object of the present invention is to provide a composition for the prevention or treatment of male pattern baldness by the adsorption and / or removal of dihydrotestosterone (DHT) and the use thereof.

[0012] Another objective of the present invention is to provide a composition for the prevention or treatment of male pattern baldness, wherein the composition comprises a metal-organic framework, and the metal-organic framework penetrates into a hair follicle to exhibit a preventive or therapeutic effect against the progression of hair loss through the adsorption / removal of DHT.

[0013] Another objective of the present invention is to provide a hair product comprising a hair serum or hair cream containing the metal-organic framework, wherein when applied to the scalp, the metal-organic framework penetrates the hair follicles to continuously adsorb and remove DHT that is continuously released from the body, and the metal-organic framework that has adsorbed and removed DHT can be expelled to the outside along with the hair growth.

[0014] To achieve the above-mentioned objective, the present invention relates to a composition for the prevention or treatment of male pattern baldness comprising a metal-organic framework (MOF).

[0015] In addition, the metal-organic framework can adsorb and / or remove dihydrotestosterone.

[0016] In addition, the metal-organic framework may have an average diameter of 500 nm or less.

[0017] Additionally, the metal-organic framework may include a metal ion or metal cluster; and at least one organic ligand that forms a bond with the metal ion.

[0018] In addition, the metal cluster may include a metal selected from the group consisting of Li, Na, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Re, Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Hg, Al, Ga, In, Tl, Si, Ge, Sn, Pb, As, Sb, and Bi.

[0019] In addition, the metal ion is Li + , Na + , Mg 2+ , Ca 2+ , Sr 2+ , Ba 2+ , Sc 3+ , Y 3+ , Ti4+ , Zr 4+ , Hf 4+ , V 4+ , V 3+ , V 2+ , Nb 3+ , Pitch 3+ , Cr 3+ , Mo 3+ , W 3+ , Mn 3+ , Mn 2+ , Re 3+ , Re 2+ , Fe 3+ , Fe 2+ , Ru 3+ , Ru 2+ , Home 3+ , Home 2+ , Co 3+ , Co 2+ , Rh 2+ , Rh + , Ir 3+ , Ir 2+ , Ir + , Knee 2+ , Knee + , Pd 2+ , Pd + , Pt 2+ , Pt + , Cu 2+ , Cu + , Ag + , Au + , Zn 2+ , Cd 2+ , Hg 2+ , Al 3+ , Ga 3+ , His 3+ , Tl 3+ , See 4+ , See 2+ , Ge 4+ , Ge 2+ , Sn 4+ , Sn 2+ , Pb 4+ , Pb 2+ , As 5+ , As 3+ , As + , Sb 5+ , Sb 3+ , Sb + , Be5+ , Bi 3+ and Bi + It can be selected from a group consisting of

[0020] In addition, the organic ligand is 1,3,5-benzenetricarboxylic acid, 4,4'-biphenyldicarboxilic acid, benzene-1,4-dicarboxylic acid, 9,10-anthracenedicarboxylic acid, biphenyl-3,3,5,5'-tetracarboxylic acid, biphenyl-3,4',5-tricarboxylic acid, 5-bromoisophthalic acid, 5-cyano-1,3-benzenedicarboxylic acid, 2,2-diamino4,4'-stilbenedicarboxylic acid, 2,5-diaminoterephthalic acid, 1,1,2,2-tetra(4-carboxylphenyl)ethylene, 2,5-dihydroxyterephthalic acid, 2,2-dinitro-4,4-stilbenedicarboxylic acid, 5-ethynyl-1,3-benzenedicarboxylic acid, 2-hydroxyterephthalic acid, 2,6-naphthalenedicarboxylic acid, 1,2,4,5-tetrakis(4-carboxyphenyl)benzene, 4,4,4''-s-triazine-2,4,6-triyl-tribenzoic acid6-triyltribenzoic acid), 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, 1,3,5-tris(4-carboxy[1,1'-biphenyl]-4-yl)benzene, 1,3,5-tris(4-carboxyphenyl)benzene, 1,3,5-tris(4-carboxyphenyl)benzene, 1,3,5-triscarboxyphenylethynylbenzene, 2-methylimidazole and It may be one or more selected from the group consisting of 2-aminoterephthalic acid.

[0021] In addition, it may include a metal-organic framework (MOF) further comprising a ligand compound represented by the following chemical formula 1:

[0022] [Chemical Formula 1]

[0023]

[0024] Here,

[0025] n is an integer of 1 or 2, and

[0026] EDP ​​refers to a group containing an electron pair donor atom, and

[0027] L1 is selected from the group consisting of a substituted or unsubstituted alkyl group having 1 to 30 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 20 carbon atoms, a substituted or unsubstituted aralkyl group having 7 to 30 carbon atoms, a substituted or unsubstituted aryl group having 6 to 30 carbon atoms, a substituted or unsubstituted heteroaryl group having 1 to 60 carbon atoms, and a substituted or unsubstituted heteroarylalkyl group having 2 to 30 carbon atoms.

[0028] In addition, the ligand compound represented by Chemical Formula 1 above may be a ligand compound represented by Chemical Formula 2 or Chemical Formula 3 below:

[0029] [Chemical Formula 2]

[0030]

[0031] [Chemical Formula 3]

[0032]

[0033] Here,

[0034] EDP ​​is as defined in Chemical Formula 1 above, and

[0035] m is an integer from 1 to 4, and

[0036] p is an integer of 0 or 1, and

[0037] L2 is selected from the group consisting of a single bond, a carbonyl group, a substituted or unsubstituted arylene group having 6 to 30 carbon atoms, a substituted or unsubstituted heteroarylene group having 1 to 30 carbon atoms, a substituted or unsubstituted alkylene group having 1 to 10 carbon atoms, a substituted or unsubstituted cycloalkylene group having 3 to 10 carbon atoms, a substituted or unsubstituted alkenylene group having 2 to 10 carbon atoms, a substituted or unsubstituted cycloalkenylene group having 3 to 10 carbon atoms, a substituted or unsubstituted heteroalkylene group having 1 to 10 carbon atoms, a substituted or unsubstituted heterocycloalkylene group having 2 to 10 carbon atoms, a substituted or unsubstituted heteroalkenylene group having 2 to 10 carbon atoms, and a substituted or unsubstituted heterocycloalkenylene group having 2 to 10 carbon atoms.

[0038] X1 and X2 are identical or different from each other, and each is independently N or C(R3), and

[0039] R1 to R3 are identical or different from one another and each independently hydrogen, deuterium, cyano group, nitro group, halogen group, hydroxyl group, substituted or unsubstituted C1 to C4 alkylthio group, substituted or unsubstituted C1 to C30 alkyl group, substituted or unsubstituted C3 to C20 cycloalkyl group, substituted or unsubstituted C2 to C30 alkenyl group, substituted or unsubstituted C2 to C24 alkynyl group, substituted or unsubstituted C7 to C30 aralkyl group, substituted or unsubstituted C6 to C30 aryl group, substituted or unsubstituted C1 to C60 heteroaryl group, substituted or unsubstituted C2 to C30 heteroarylalkyl group, substituted or unsubstituted C1 to C30 alkoxy group, substituted or unsubstituted C1 to C30 of It is selected from the group consisting of an alkylamino group, a substituted or unsubstituted arylamino group having 6 to 30 carbon atoms, a substituted or unsubstituted aralkylamino group having 7 to 30 carbon atoms, a substituted or unsubstituted heteroarylamino group having 1 to 24 carbon atoms, a substituted or unsubstituted alkylsilyl group having 1 to 30 carbon atoms, a substituted or unsubstituted arylsilyl group having 6 to 30 carbon atoms, and a substituted or unsubstituted aryloxy group having 6 to 30 carbon atoms.

[0040] Another invention for achieving the above-mentioned purpose may be a cosmetic composition comprising the above-mentioned composition for the prevention or treatment of male pattern baldness.

[0041] In addition, the cosmetic composition is applied to the hair and / or scalp for use, and the metal-organic framework (MOF) contained in the cosmetic composition can penetrate the hair follicles to adsorb and / or remove dihydrotestosterone.

[0042] In addition, the metal-organic framework within the hair follicle can adsorb and / or remove dihydrotestosterone for more than 24 hours.

[0043] In addition, the metal-organic framework that adsorbs and / or removes dihydrotestosterone within the hair follicle can be expelled externally as the hair grows.

[0044] In the present invention, “hydrogen” is hydrogen, light hydrogen, deuterium, or tritium unless specifically limited otherwise.

[0045] In the present invention, the “halogen group” is fluorine, chlorine, bromine, or iodine.

[0046] In the present invention, “alkyl” refers to a monovalent substituent derived from a straight-chain or side-chain saturated hydrocarbon having 1 to 40 carbon atoms. Examples thereof include, but are not limited to, methyl, ethyl, propyl, isobutyl, sec-butyl, pentyl, iso-amyl, hexyl, etc.

[0047] In the present invention, “alkenyl” refers to a monovalent substituent derived from a straight-chain or side-chain unsaturated hydrocarbon having 2 to 40 carbon atoms and one or more carbon-carbon double bonds. Examples thereof include, but are not limited to, vinyl, allyl, isopropenyl, and 2-butenyl.

[0048] In the present invention, “alkynyl” refers to a monovalent substituent derived from a straight-chain or side-chain unsaturated hydrocarbon having 2 to 40 carbon atoms and one or more carbon-carbon triple bonds. Examples thereof include, but are not limited to, ethynyl and 2-propynyl.

[0049] In the present invention, "alkylthio" refers to the alkyl group described above bonded through a sulfur linkage (-S-).

[0050] In the present invention, “aryl” refers to a monovalent substituent derived from an aromatic hydrocarbon having 6 to 60 carbon atoms, consisting of a single ring or a combination of two or more rings. Additionally, forms in which two or more rings are simply pendent or condensed may be included. Specifically, they may be naphthyl groups, anthracenyl groups, phenanthryl groups, triphenyl groups, pyrenyl groups, phenalenyl groups, perylenyl groups, chrysenyl groups, fluorenyl groups, etc., but are not limited thereto. The fluorenyl groups may be substituted, and adjacent groups may combine to form a ring.

[0051] In the present invention, “heteroaryl” refers to a monovalent substituent derived from a monoheterocyclic or polyheterocyclic aromatic hydrocarbon having 6 to 30 carbon atoms. In this case, one or more carbons in the ring, preferably 1 to 3 carbons, are substituted with heteroatoms such as N, O, S, or Se. Additionally, forms in which two or more rings are simply pendent or condensed with each other may be included, and furthermore, forms condensed with an aryl group may also be included. Examples of such heteroaryls include, but are not limited to, 6-membered monocyclic rings such as pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and triazinyl; polycyclic rings such as phenoxathienyl, indolizinyl, indolyl, purinyl, quinolyl, benzothiazole, and carbazolyl; and 2-furanyl, N-imidazolyl, 2-isoxazolyl, 2-pyridinyl, and 2-pyrimidinyl.

[0052] In the present invention, “aryloxy” refers to a monovalent substituent represented by RO-, where R means an aryl having 6 to 60 carbon atoms. Examples of such aryloxy include, but are not limited to, phenyloxy, naphthyloxy, and diphenyloxy.

[0053] In the present invention, “alkyloxy” refers to a monovalent substituent represented by R’O-, where R’ means an alkyl group having 1 to 40 carbon atoms, and may include a linear, branched, or cyclic structure. Examples of alkyloxy include, but are not limited to, methoxy, ethoxy, n-propoxy, 1-propoxy, t-butoxy, n-butoxy, pentoxy, etc.

[0054] In the present invention, the “alkoxy” may be a straight chain, a branched chain, or a cyclic chain. The number of carbon atoms in the alkoxy is not particularly limited, but it is preferred to have 1 to 20 carbon atoms. Specifically, it may be methoxy, ethoxy, n-propoxy, isopropoxy, i-propyloxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentyloxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutyloxy, 2-ethylbutyloxy, n-octyloxy, n-nonyloxy, n-decyloxy, benzyloxy, p-methylbenzyloxy, etc., but is not limited thereto.

[0055] In the present invention, "aralkyl" refers to an aryl-alkyl group such as aryl and alkyl as described above. Preferred aralkyls include lower alkyl groups. Non-limiting examples of suitable aralkyl groups include benzyl, 2-phenethyl, and naphthalenylmethyl. Bonding to the parent residue is made through alkyl groups.

[0056] In the present invention, “arylamino group” means an amine substituted with an aryl group having 6 to 30 carbon atoms.

[0057] In the present invention, “alkylamino group” means an amine substituted with an alkyl group having 1 to 30 carbon atoms.

[0058] In the present invention, “aralkylamino group” means an amine substituted with an aryl-alkyl group having 6 to 30 carbon atoms.

[0059] In the present invention, “heteroarylamino group” means an amine group substituted with an aryl group having 6 to 30 carbon atoms and a heterocyclic group.

[0060] In the present invention, “heteroaralkyl group” refers to an aryl-alkyl group substituted with a heterocyclic group.

[0061] In the present invention, “cycloalkyl” refers to a monovalent substituent derived from a monocyclic or polycyclic non-aromatic hydrocarbon having 3 to 40 carbon atoms. Examples of such cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and adamantine.

[0062] In the present invention, “heterocycloalkyl” refers to a monovalent substituent derived from a non-aromatic hydrocarbon having 3 to 40 carbon atoms, wherein one or more carbons in the ring, preferably 1 to 3 carbons, are substituted with heteroatoms such as N, O, S, or Se. Examples of such heterocycloalkyls include, but are not limited to, morpholine and piperazine.

[0063] In the present invention, “alkylsilyl” means a silyl substituted with an alkyl group having 1 to 40 carbon atoms, and “arylsilyl” means a silyl substituted with an aryl group having 6 to 60 carbon atoms.

[0064] In the present invention, “condensed ring” means a condensed aliphatic ring, a condensed aromatic ring, a condensed heteroaliphatic ring, a condensed heteroaromatic ring, or a combination thereof.

[0065] In the present invention, "forming a ring by combining with adjacent groups" means combining with adjacent groups to form a substituted or unsubstituted aliphatic hydrocarbon ring; a substituted or unsubstituted aromatic hydrocarbon ring; a substituted or unsubstituted aliphatic heteroring; a substituted or unsubstituted aromatic heteroring; or a condensed ring thereof.

[0066] Examples of “aromatic hydrocarbon rings” in the present invention include phenyl groups, naphthyl groups, anthracenyl groups, etc., but are not limited to these.

[0067] In the present invention, “aliphatic heterocycle” means an aliphatic ring containing one or more heteroatoms.

[0068] In the present invention, "aromatic heterocycle" means an aromatic ring containing one or more heteroatoms.

[0069] In the present invention, "substitution" means that a hydrogen atom bonded to a carbon atom of a compound is replaced with another substituent, and the substitution location is not limited to the location where the hydrogen atom is substituted, that is, any location where a substituent can be substituted, and in the case of two or more substitutions, the two or more substituents may be the same or different from each other. The above substituents are hydrogen, a cyano group, a nitro group, a halogen group, a hydroxyl group, an alkyl group having 1 to 30 carbon atoms, an alkenyl group having 2 to 30 carbon atoms, an alkynyl group having 2 to 24 carbon atoms, a heteroalkyl group having 2 to 30 carbon atoms, an aralkyl group having 6 to 30 carbon atoms, an aryl group having 5 to 30 carbon atoms, a heteroaryl group having 2 to 30 carbon atoms, a heteroarylalkyl group having 3 to 30 carbon atoms, an alkoxy group having 1 to 30 carbon atoms, an alkylamino group having 1 to 30 carbon atoms, an arylamino group having 6 to 30 carbon atoms, an aralkylamino group having 6 to 30 carbon atoms, a heteroarylamino group having 2 to 24 carbon atoms, a substituted or unsubstituted alkylsilyl group having 1 to 30 carbon atoms, a substituted or unsubstituted substituent having 6 to 30 carbon atoms It may be substituted with one or more substituents selected from the group consisting of an arylsilyl group and a substituted or unsubstituted aryloxy group having 6 to 30 carbon atoms, but is not limited to the above examples.

[0070] The present invention relates to a composition for the prevention or treatment of male pattern baldness comprising a metal-organic framework, wherein the metal-organic framework penetrates into the hair follicle and, through the adsorption / removal of DHT, can exhibit an effect of preventing or treating the progression of hair loss.

[0071] In addition, when a hair serum or hair cream containing the above metal-organic framework is applied to the scalp, the metal-organic framework penetrates the hair follicles and can continuously adsorb / remove DHT that is continuously released from the body, and the metal-organic framework that has adsorbed / remove DHT can be expelled to the outside along with the hair growth.

[0072] Figure 1 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0073] Figure 2 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0074] Figure 3 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0075] Figure 4 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0076] Figure 5 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0077] Figure 6 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0078] Figure 7 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0079] Figure 8 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0080] Figure 9 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0081] Figure 10 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0082] Figure 11 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0083] Figure 12 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0084] Figure 13 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0085] Figure 14 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0086] Figure 15 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0087] Figure 16 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0088] Figure 17 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0089] Figure 18 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0090] FIG. 19 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0091] FIG. 20 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0092] FIG. 21 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0093] FIG. 22 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0094] FIG. 23 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0095] FIG. 24 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0096] FIG. 25 is the result of evaluating the amount of DHT adsorbed by a metal-organic framework according to one embodiment of the present invention.

[0097] Figure 26 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0098] Figure 27 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0099] Figure 28 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0100] FIG. 29 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0101] FIG. 30 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0102] Figure 31 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0103] Figure 32 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0104] Figure 33 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0105] Figure 34 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0106] FIG. 35 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0107] Figure 36 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0108] Figure 37 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0109] FIG. 38 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0110] FIG. 39 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0111] Figure 40 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0112] Figure 41 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0113] Figure 42 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0114] Figure 43 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0115] Figure 44 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0116] Figure 45 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0117] Figure 46 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0118] Figure 47 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0119] FIG. 48 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0120] Figure 49 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0121] FIG. 50 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0122] Figure 51 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0123] Figure 52 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0124] Figure 53 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0125] Figure 54 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0126] Figure 55 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0127] Figure 56 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0128] FIG. 57 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0129] Figure 58 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0130] FIG. 59 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0131] FIG. 60 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0132] Figure 61 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0133] FIG. 62 is a scanning electron microscope observation result of a metal-organic framework according to one embodiment of the present invention.

[0134] Figure 63 is the result of X-ray diffraction analysis of a metal-organic framework according to one embodiment of the present invention.

[0135] Figure 64 is the result of BET analysis through N2 adsorption of a metal-organic framework according to one embodiment of the present invention.

[0136] FIG. 65 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the invention.

[0137] FIG. 66 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0138] FIG. 67 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0139] FIG. 68 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0140] FIG. 69 is the result of an evaluation of the cytotoxicity of a metal-organic framework according to one embodiment of the present invention.

[0141] FIG. 70 is the result of an evaluation of the cytotoxicity of a metal-organic framework according to one embodiment of the present invention.

[0142] FIG. 71 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0143] FIG. 72 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0144] FIG. 73 is the result of an evaluation of the cytotoxicity of a metal-organic framework according to one embodiment of the present invention.

[0145] FIG. 74 is the result of an evaluation of the cytotoxicity of a metal-organic framework according to one embodiment of the present invention.

[0146] FIG. 75 is the result of an evaluation of the cytotoxicity of a metal-organic framework according to one embodiment of the present invention.

[0147] FIG. 76 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0148] FIG. 77 is the result of a cytotoxicity evaluation of a metal-organic framework according to one embodiment of the present invention.

[0149] FIG. 78 is the result of evaluating the amount of DHT adsorbed by a metal-organic framework according to one embodiment of the invention.

[0150] The present invention relates to a composition for the prevention or treatment of male pattern baldness comprising a metal-organic framework (MOF).

[0151] Hereinafter, embodiments of the present invention are described in detail so that those skilled in the art can easily implement the invention. However, the present invention may be embodied in various different forms and is not limited to the embodiments described herein.

[0152] DHT is an abbreviation for dihydrotestosterone, a male hormone. It is a substance produced when testosterone present in the blood is converted by the 5α-reductase enzyme in the hair follicles. When the amount of DHT increases beyond what is necessary, it acts on the hair follicles to cause hair loss. DHT is a substance that regulates hair growth; it binds to androgen receptors to regulate hair growth and is involved in the proliferation of sebaceous glands.

[0153] More specifically, the hair loss process caused by DHT occurs when DHT binds to androgen receptors in the hair papillae located on the forehead and crown, transmitting a cell destruction signal to the DNA of hair matrix cells. This signal triggers the production of apoptosis factors, specifically DKK-1 and TGF-β1, which destroy the hair matrix cells, cause them to enter the regression phase, and result in hair loss.

[0154] In men with hair loss affected by the aforementioned DHT, thick hair from the forehead to the crown is replaced by thin and brittle hair. This is due to a shortened hair growth phase. The pattern of hair loss involves the hairline receding in an M-shape or hair shedding starting from the crown. Hair on the back of the head or on both sides of the head is not affected by DHT.

[0155] Based on this process, it is important to prevent DHT in the scalp from binding to androgen receptors in the hair papilla.

[0156] Therefore, while 'DHT-inhibiting shampoos' claim that the action of DHT can be easily blocked through home care, it is virtually impossible to prevent the production of DHT using shampoo alone. This is because shampoo is intended merely to promote scalp cleanliness and hair health, and it is impossible to expect the inhibitory effect on DHT production based on the aforementioned mechanism from using shampoo.

[0157] Accordingly, the present invention aims to exhibit a preventive or therapeutic effect against male pattern baldness by penetrating into the hair follicles of the scalp and adsorbing and / or removing DHT. Specifically, the composition for the prevention or treatment of male pattern baldness according to the present invention may include a metal-organic framework (MOF).

[0158] The metal-organic framework described above can adsorb and / or remove dihydrotestosterone (DHT). To this end, the metal-organic framework must be able to penetrate into the hair follicle, and to this end, the average diameter of the metal-organic framework may be 500 nm or less, 450 nm or less, 400 nm or less, 350 nm or less, and 300 nm or less. Preferably, it may be in the range of 10 nm to 300 nm. However, the metal-organic framework is intended to have an appropriate diameter for penetrating into the hair follicle, and accordingly, when the average diameter is 500 nm or less, it can penetrate into the hair follicle and adsorb and / or remove DHT.

[0159] The hair follicle mentioned above is a skin organ that produces hair. The pore is the opening of the hair, and it can penetrate into the hair follicle through the pore. On average, the pore is known to have a size of 0.02 to 0.05 mm, so a metal-organic framework having the aforementioned average diameter can easily penetrate into the hair follicle through the pore. As described above, the metal-organic framework that has penetrated into the hair follicle can adsorb DHT, and as described below, the metal-organic framework that has adsorbed DHT comes out through the pore along with the growth of the hair, and the metal-organic framework that has come out through the pore can be easily removed by washing the hair.

[0160] The above metal-organic framework is formed by coordination bonding between a metal ion or metal cluster and an organic ligand or linker. Specifically, a "metal-organic framework (MOF)" refers to a porous material in which metal clusters and organic linkers (or organic bridging ligands) are connected by coordination bonds to form a three-dimensional structure, and various MOFs can be created depending on the selection of metal ions and organic ligands. The MOF is characterized by its porosity, which contains empty spaces within its structure, and the pore size, porosity, three-dimensional structure, and surface area can be designed in various ways depending on the types and bonding methods of the metal ions and organic ligands constituting the MOF. Due to this porosity, MOFs not only have a very large surface area but also possess an open pore structure, which enables the movement of large amounts of molecules or solvents compared to other previously known porous materials. Furthermore, when used as catalysts or gas storage materials, they have the advantage of maximizing efficiency due to the abundance of active sites. In addition, the MOF does not easily deform at high temperatures and possesses a rigid framework, resulting in excellent chemical and thermal stability.

[0161] The above metal cluster is specifically a metal selected from the group consisting of Li, Na, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Re, Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Hg, Al, Ga, In, Tl, Si, Ge, Sn, Pb, As, Sb, and Bi, or Li + , Na + , Mg 2+ , Ca 2+ , Sr 2+ , Ba 2+ , Sc3+ , Y 3+ , You 4+ , Zr 4+ , Hf 4+ , V 4+ , V 3+ , V 2+ , Nb 3+ , Yes 3+ , Cr 3+ , My 3+ , W 3+ , Mr. 3+ , Mr. 2+ , Re 3+ , Re 2+ , Fe 3+ , Fe 2+ , Ru 3+ , Ru 2+ , If 3+ , If 2+ , Co 3+ , Co 2+ , Rh 2+ , Rh + , Ireland 3+ , Ireland 2+ , Ireland + , We 2+ , We + , Pd 2+ , Pd + , Pt 2+ , Pt + , Dog 2+ , Dog + , At + , Oh + , Zn 2+ , CD 2+ , Hg 2+ , Al 3+ , Ga 3+ , In 3+ , Tl 3+ , Yes 4+ , Yes 2+ , Ge 4+ , Ge 2+ , Sn 4+ , Sn 2+ , Pb 4+ , Pb 2+ , As 5+ , As 3+ , As + , Sb 5+ , Sb3+ , Sb + , Bi 5+ , Bi 3+ and Bi + It may include metal ions selected from the group consisting of

[0162] More specifically, the metal-organic framework may be selected from the group consisting of aluminum-based metal-organic frameworks, iron-based metal-organic frameworks, zirconium-based metal-organic frameworks, and mixtures thereof, and preferably may be a zirconium-based metal-organic framework or an iron-based metal-organic framework.

[0163] In addition, the organic ligand is 1,3,5-benzenetricarboxylic acid, 4,4'-biphenyldicarboxilic acid, benzene-1,4-dicarboxylic acid, 9,10-anthracenedicarboxylic acid, biphenyl-3,3,5,5'-tetracarboxylic acid, biphenyl-3,4',5-tricarboxylic acid, 5-bromoisophthalic acid, 5-cyano-1,3-benzenedicarboxylic acid, 2,2-diamino4,4'-stilbenedicarboxylic acid, 2,5-diaminoterephthalic acid, 1,1,2,2-tetra(4-carboxylphenyl)ethylene, 2,5-dihydroxyterephthalic acid, 2,2-dinitro-4,4-stilbenedicarboxylic acid, 5-ethynyl-1,3-benzenedicarboxylic acid, 2-hydroxyterephthalic acid, 2,6-naphthalenedicarboxylic acid, 1,2,4,5-tetrakis(4-carboxyphenyl)benzene, 4,4,4''-s-triazine-2,4,6-triyl-tribenzoic acidIt may be one or more selected from the group consisting of 4,6-triyltribenzoic acid), 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, 1,3,5-tris(4-carboxy[1,1'-biphenyl]-4-yl)benzene, 1,3,5-tris(4-carboxyphenyl)benzene, and 1,3,5-triscarboxyphenylethynylbenzene, but is not limited thereto.

[0164] The above metal-organic framework may be selected from the group consisting of UIO66, UIO66-NH2, UIO67, UIO67-NH2, PCN128, PCN222, PCN223, PCN224, MOF525, MOF545, MOF801, MOF808, MOF867, Fe-MIL53, Fe-MIL53-NH2, Fe-MIL88, Fe-MIL88-NH2, Fe-MIL100, Fe-MIL100-NH2, Fe-MIL101, Fe-MIL101-NH2, Fe-MIL125, and Fe-MIL125-NH2, and preferably may be selected from the group consisting of PCN223, MOF525, UIO66, MOF808, UIO67, and Fe-MIL88-NH2, but the above examples Any metal-organic framework capable of penetrating into hair follicles and adsorbing and removing DHT can be used without limitation.

[0165] In the present invention, in addition to the metal-organic framework described above, a novel metal-organic framework in which a novel ligand compound is additionally bonded to the metal-organic framework can be used as a composition for the prevention or treatment of male pattern baldness. The novel ligand compound may be a compound represented by the following chemical formula 1:

[0166] [Chemical Formula 1]

[0167]

[0168] Here,

[0169] n is an integer of 1 or 2, and

[0170] EDP ​​refers to a group containing an electron pair donor atom, and

[0171] L1 is selected from the group consisting of a substituted or unsubstituted alkyl group having 1 to 30 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 20 carbon atoms, a substituted or unsubstituted aralkyl group having 7 to 30 carbon atoms, a substituted or unsubstituted aryl group having 6 to 30 carbon atoms, a substituted or unsubstituted heteroaryl group having 1 to 60 carbon atoms, and a substituted or unsubstituted heteroarylalkyl group having 2 to 30 carbon atoms.

[0172] The above-described organic ligand means that it is bound to a metal cluster or a metal ion, and the ligand compound represented by the above chemical formula 1 can be coordinately bound to a metal-organic framework in which a metal cluster or a metal ion is bound by the organic ligand.

[0173] The ligand compound represented by the above chemical formula 1 may be a ligand compound represented by the following chemical formula 2 or chemical formula 3:

[0174] [Chemical Formula 2]

[0175]

[0176] [Chemical Formula 3]

[0177]

[0178] Here,

[0179] The EDP is as defined in Paragraph 1, and

[0180] m is an integer from 1 to 4, and

[0181] p is an integer of 0 or 1, and

[0182] L2 is selected from the group consisting of a single bond, a carbonylene group, a substituted or unsubstituted arylene group having 6 to 30 carbon atoms, a substituted or unsubstituted heteroarylene group having 1 to 30 carbon atoms, a substituted or unsubstituted alkylene group having 1 to 10 carbon atoms, a substituted or unsubstituted cycloalkylene group having 3 to 10 carbon atoms, a substituted or unsubstituted alkenylene group having 2 to 10 carbon atoms, a substituted or unsubstituted cycloalkenylene group having 3 to 10 carbon atoms, a substituted or unsubstituted heteroalkylene group having 1 to 10 carbon atoms, a substituted or unsubstituted heterocycloalkylene group having 2 to 10 carbon atoms, a substituted or unsubstituted heteroalkenylene group having 2 to 10 carbon atoms, and a substituted or unsubstituted heterocycloalkenylene group having 2 to 10 carbon atoms.

[0183] X1 and X2 are identical or different from each other, and each is independently N or C(R3), and

[0184] R1 to R3 are identical or different from one another and each independently hydrogen, deuterium, cyano group, nitro group, halogen group, hydroxyl group, substituted or unsubstituted C1 to C4 alkylthio group, substituted or unsubstituted C1 to C30 alkyl group, substituted or unsubstituted C3 to C20 cycloalkyl group, substituted or unsubstituted C2 to C30 alkenyl group, substituted or unsubstituted C2 to C24 alkynyl group, substituted or unsubstituted C7 to C30 aralkyl group, substituted or unsubstituted C6 to C30 aryl group, substituted or unsubstituted C1 to C60 heteroaryl group, substituted or unsubstituted C2 to C30 heteroarylalkyl group, substituted or unsubstituted C1 to C30 alkoxy group, substituted or unsubstituted C1 to C30 of It is selected from the group consisting of an alkylamino group, a substituted or unsubstituted arylamino group having 6 to 30 carbon atoms, a substituted or unsubstituted aralkylamino group having 7 to 30 carbon atoms, a substituted or unsubstituted heteroarylamino group having 1 to 24 carbon atoms, a substituted or unsubstituted alkylsilyl group having 1 to 30 carbon atoms, a substituted or unsubstituted arylsilyl group having 6 to 30 carbon atoms, and a substituted or unsubstituted aryloxy group having 6 to 30 carbon atoms.

[0185] The above EDP is more specifically -NO 2, Groups comprising electron pair donor atoms capable of coordinate bonding with metal clusters may be selected from the group consisting of -NH2, -OH, -COOH, -OCH3 and mixtures thereof, but are not limited to the above examples, and any group comprising electron pair donor atoms capable of coordinate bonding with metal clusters may be selected.

[0186] The compound represented by the above chemical formula 2 may be selected from the group consisting of compounds represented by the following chemical formulas 4 to 10:

[0187] [Chemical Formula 4]

[0188]

[0189] [Chemical Formula 5]

[0190]

[0191] [Chemical Formula 6]

[0192]

[0193] [Chemical Formula 7]

[0194]

[0195] [Chemical Formula 8]

[0196]

[0197] [Chemical Formula 9]

[0198]

[0199] [Chemical Formula 10]

[0200]

[0201] [Chemical Formula 11]

[0202]

[0203] [Chemical Formula 12]

[0204]

[0205] The compound represented by the above chemical formula 3 may be selected from the group consisting of compounds represented by the following chemical formulas 13 to 15:

[0206] [Chemical Formula 13]

[0207]

[0208] [Chemical Formula 14]

[0209]

[0210] [Chemical Formula 15]

[0211]

[0212] A composition for the prevention or treatment of male pattern baldness according to another embodiment of the present invention may include the novel metal-organic framework.

[0213] A cosmetic composition according to another embodiment of the present invention may include the composition for preventing or treating male pattern baldness.

[0214] As described above, the cosmetic composition comprises a composition for the prevention or treatment of male pattern baldness containing a metal-organic framework. The cosmetic composition is applied to the hair and / or scalp for use, and the metal-organic framework contained within the cosmetic composition can penetrate into hair follicles to adsorb and / or remove DHT. By penetrating into the hair follicles as described above and adsorbing and removing DHT, it can exhibit a preventive or therapeutic effect against hair loss.

[0215] In addition, the metal-organic framework can penetrate into the hair follicle and adsorb and remove DHT for more than 24 hours. As described above, the metal-organic framework has a porous characteristic with empty spaces within its structure, which allows it to exhibit an excellent adsorption effect, and when it penetrates into the hair follicle, it can exert an excellent adsorption effect on DHT for a long time. As DHT is continuously adsorbed and removed from the hair follicle for 24 hours, the cosmetic composition of the present invention can exhibit a preventive or therapeutic effect against hair loss by using it once a day.

[0216] As described above, the metal-organic framework that adsorbs and / or removes DHT within the hair follicle can be expelled externally as the hair grows. That is, if the metal-organic framework within the hair follicle continuously penetrates without being expelled externally due to the repeated use of the cosmetic composition described above, a problem of hair follicle blockage may occur. In other words, if the metal-organic framework is not expelled externally from the hair follicle, it acts as waste within the follicle, which can cause problems such as folliculitis. However, the metal-organic framework of the present invention can be expelled to the scalp as the hair grows, and the metal-organic framework expelled to the scalp can be easily removed by washing the hair. That is, it can be easily removed using hair cleansing products such as shampoo.

[0217] The cosmetic composition of the present invention may be prepared in any formulation that can be conventionally applied to the scalp and hair, such as a liquid, cream, paste, or solid form, and may be prepared in formulations such as hair lotion, hair tonic, hair soap, hair pack, hair serum, hair cream, or liquid hair growth agent type for the prevention or treatment of hair loss by adding conventional additives. It is preferable to use the cosmetic composition of the present invention by a transdermal administration method, such as by direct application or spraying to the scalp or hair.

[0218] In addition to the metal-organic framework described above, the cosmetic composition of the present invention may add base components that can be incorporated into general topical formulations for the scalp and hair as needed. Specifically, these include solubilizing agents, surfactants, moisturizers, thickeners, pH adjusters, preservatives, antioxidants, metal ion chelating agents, fungicides, anti-inflammatory agents, antimicrobial agents, solvents, coloring agents, and flavoring agents.

[0219] Specifically, the above solubilizing agent may be isopropyl myristate, polyethylene glycol, medium-chain fatty acid triglyceride hydrocarbons, glycols, etc.

[0220] Among the above surfactants, the anionic surfactants may specifically be ammonium lauryl sulfosuccinate, ammonium lauryl sulfate, sodium cocoyl sessionate, sodium lauryl sessionate, sodium lauryl sulfate, triethanolamine lauryl sulfate, sodium lauryl ether sulfate (1 to 3 ethylene oxides), etc. Among the surfactants, the nonionic surfactants may specifically be polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene, hydrogenated castor oil derivative, fatty acid diethanolamide, glyceryl stearate, etc. Among the surfactants, the cationic surfactants may specifically be tertiary aliphatic amine salts, alkyltrimethylammonium chloride, dialkyldimethylammonium chloride, etc. Among surfactants, amphoteric surfactants can specifically be betaine, amide betaine type, sulfo betaine type, steartrimonium chloride, etc.

[0221] The above moisturizer may specifically be glycerin, propylene glycol, 1,3-butylene glycol, dipropylene glycol, sorbitol, etc.

[0222] Specifically, the above-mentioned thickening agent may be a water-soluble polymer compound such as methylcellulose, hydroxyethylcellulose, carrageenan, carboxymethylcellulose, or hydroxymethylcellulose.

[0223] The above pH adjuster may specifically be citric acid, sodium hydroxide, triethanolamine, sodium citrate, phosphoric acid, sodium phosphate, lactic acid, etc.

[0224] Specifically, the above preservatives may be a mixture of benzoic acid, para-hydroxybenzoic acid ester, and methylchloroisothiazolinone, phenoxyethanol, DMDM ​​hydantoin, etc.

[0225] The above antioxidant may specifically be dibutylhydroxytoluene, ascorbic acid, etc.

[0226] Specifically, the above solvent may be ethanol, purified water, Tween 20, cyclomethicone, mineral oil, dimethicone, etc. The above coloring agent and flavoring agent may use bases commonly used in formulations for the scalp and hair.

[0227] As for other base ingredients, any that are typically used in topical formulations for the scalp and hair may be used without restriction.

[0228] Preparation Example

[0229] Preparation of metal-organic frameworks

[0230] PCN223 synthesis

[0231] 100 mg of TCPP (tetrakis(4-carboxyphenyl)porphyrin), 195 mg of ZrOCl2*8H2O (zirconyl chloride octahydrate), and 10 ml of acetic acid were added to 320 ml of DMF and dissolved. Subsequently, the mixture was reacted at 90°C for 17 hours. The synthesized particles were washed three times each with DMF and ethanol, and dried at 80°C to obtain a powder.

[0232] MOF525 synthesis

[0233] 90 mg of TCPP (tetrakis(4-carboxyphenyl)porphyrin), 145 mg of ZrOCl2*8H2O (zirconyl chloride octahydrate), and 1 ml of dichloroacetic acid were added to 250 ml of DMF and dissolved. Subsequently, the mixture was reacted at 100°C for 48 hours. The synthesized particles were washed three times each with DMF and ethanol, and dried at 80°C to obtain a powder.

[0234] UIO66 Synthetic

[0235] 3.6 g of benzoic acid, 1.2 g of BDC (Benzene-1,4-dicarboxylic acid), and 8.12 g of ZrCl4 (Zirconium(IV) chloride) were added to 350 ml of DMF and dissolved. Subsequently, the mixture was reacted at 110°C for 24 hours. The synthesized particles were washed three times each with DMF and ethanol, and dried at 80°C to obtain a powder.

[0236] MOF808 synthesis

[0237] 96 mg of 1,3,5-BTC (1,3,5-Benzenetricarboxylic acid), 64 mg of ZrOCl2 (Zirconium(IV) oxide chloride), and 5.3 ml of formic acid were added to 150 ml of DMF and dissolved. Subsequently, the mixture was reacted at 180°C for 36 hours. The synthesized particles were washed three times each with DMF and ethanol, and dried at 80°C to obtain a powder.

[0238] UIO67 synthesis

[0239] 140 mg of BPDC (4,4'-Biphenyldicarboxylic acid) and 130 mg of ZrCl4 (Zirconium(IV) chloride) were added to 380 ml of DMF and dissolved. The mixture was reacted at 90°C for 17 hours. The synthesized particles were washed three times each with DMF and ethanol, and dried at 80°C to obtain a powder.

[0240] MIL88NH2 synthesis

[0241] 464 mg of 2-aminoterephthalic acid, 74 mg of FeCl3*6H2O (Iron(III) chloride hexahydrate), 2 ml of acetic acid, and 16 g of Pluronic® F127 were added to 100 ml of DMF and dissolved. Subsequently, the mixture was reacted at 180°C for 24 hours. The synthesized particles were washed three times each with DMF and ethanol, and dried at 80°C to obtain a powder.

[0242] Experimental Example 1

[0243] Synthesis result analysis

[0244] To measure using a Scanning Electron Microscope (SEM), a powder sample was placed in a 2 mg to 3 mg Eppen tube, 100 µl of ethanol was added, and bath sonification was performed. Subsequently, 10 µl was spot-dried onto a silicon wafer and dried in an 80°C oven. The silicon wafer with the dried sample was then attached to the SEM mount using carbon tape and transferred to the SEM instrument to measure images (Company: Zeiss / Model: ULTRA PLUS).

[0245] Next, for X-ray diffraction (XRD) measurement, the powder sample was carefully placed on the XRD sample holder and compressed by pressing it with a glass slide glass with appropriate force. Afterward, all powder scattered around the sample holder was carefully removed, the sample holder was transferred to the equipment and set up, and measurements were performed in the range of 2°C to 30°C (Company: Bruker / Model: D2 phaser).

[0246] Next, for N2 adsorption isotherms and BET specific surface area-pore measurements, approximately 40 mg of a completely dried sample was prepared and carefully placed into a glass sampler using a glass funnel. All powder adhering to the area around the glass tube and the sample container at the bottom was removed. Subsequently, the top filter cap was attached, and degassing was performed in a pretreatment apparatus under vacuum and heat treatment at 120°C for 12 hours. The weight of the pretreated sample was measured using a microbalance, and the weight of the intact sample was calculated by subtracting the weight of the previously measured empty cell. The glass sampler was mounted on the N2 adsorption-desorption apparatus, and measurements were performed (Company Name: MICROTAAC / Model Name: BELSORP MINI X).

[0247] Scanning electron microscope (SEM) observation results for the above PCN223 are shown in Fig. 1. In addition, X-ray diffraction analysis results are shown in Fig. 2, confirming that the prepared particles were synthesized with the crystal structure of PCN223. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 3. The specific surface area of ​​the PCN223 particles analyzed through these methods is 2273.6 m². 2 / g is.

[0248] Furthermore, the scanning electron microscope (SEM) observation results for the MOF525 are shown in Fig. 4. Additionally, the X-ray diffraction analysis results are shown in Fig. 5, confirming that the prepared particles were synthesized with the crystal structure of MOF525. Moreover, the BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 6. The specific surface area of ​​the MOF525 particles analyzed through these methods is 1356.3 m². 2 / g is.

[0249] In addition, the scanning electron microscope (SEM) observation and X-ray diffraction (XD) analysis results of the above UIO66 are shown in Figures 7 and 8. Through this, it was confirmed that the prepared particles were synthesized having the crystal structure of UIO66. The BET analysis results are shown in Figure 9, and the specific surface area is 1423.8 m².2 / g is.

[0250] In addition, the scanning electron microscope (SEM) observation and X-ray diffraction (XD) analysis results of the MOF808 are shown in Figures 10 and 11. Through this, it was confirmed that the prepared particles were synthesized with the crystal structure of MOF808. The BET analysis results are shown in Figure 12, and the specific surface area is 1582.4 m². 2 / g is.

[0251] In addition, the scanning electron microscope (SEM) observation and X-ray diffraction (XD) analysis results of the above UIO67 are shown in Figs. 13 and 14. Through this, it was confirmed that the prepared particles were synthesized having the crystal structure of UIO67. The BET analysis results are shown in Fig. 15, and the specific surface area is 2192.8 m². 2 / g is.

[0252] In addition, the scanning electron microscope (SEM) observation and X-ray diffraction (XD) analysis results of the above MIL88-NH2 are shown in Figures 16 and 17. Through this, it was confirmed that the prepared particles were synthesized having the crystal structure of MIL88-NH2. The BET analysis results are shown in Figure 18, and the specific surface area is 233.5 m². 2 / g is.

[0253] Experimental Example 2

[0254] Cytotoxicity Assessment

[0255] L929 (mouse fibroblasts) were seeded into a 96-well plate at a density of 10,000 cells / well and cultured for 24 hours in a 37°C, 5% CO2 incubator. After 24 hours, the existing medium was removed from each well, and test solutions were prepared by suspending the particles to be tested in the medium at concentrations of 100, 50, 25, 10, 5, and 1 µg / ml. 100 µl of these solutions were then added to each well. After incubating for 24 hours in a 37°C, 5% CO2 incubator, the medium was removed and the cells were washed three times with PBS. 10% EZ-cytox medium was added to each well and incubated for 1 hour. Absorbance at 450 nm and 600 nm was measured using a microplate reader to compare cell viability with that of the control group.

[0256] The test results are as shown in Figures 19 to 24. Figure 19 shows the cytotoxicity evaluation of PCN223 at different concentrations, Figure 20 shows the cytotoxicity evaluation of MOF525 at different concentrations, Figure 21 shows the cytotoxicity evaluation of UIO66 at different concentrations, Figure 22 shows the cytotoxicity evaluation of MOF808 at different concentrations, Figure 23 shows the cytotoxicity evaluation of UIO67 at different concentrations, and Figure 24 shows the cytotoxicity evaluation of MIL88-NH2 at different concentrations. According to the above test results, it was confirmed that more than 80% of the cells survived across the entire concentration range for the majority of MOFs, confirming that they are safe substances without cytotoxicity.

[0257] Experimental Example 3

[0258] DHT adsorption evaluation

[0259] DHT (4,5a-Dihydrotestosterone) was prepared using EtOH at a concentration of 500 µg / ml. 50 mg of the MOF from the above preparation example was added to 1 ml of the above DHT solution. It was left at room temperature for 24 hours. Afterward, the supernatant was taken and centrifuged at 17,000 rpm for 5 minutes to remove particles, and then the DHT concentration of the supernatant was measured. After measuring the concentration of the DHT solution prepared above, the DHT concentration of the sample supernatant was subtracted to determine the concentration and content of DHT adsorbed on the MOF.

[0260] The HPLC measurement conditions are as follows.

[0261] Mobile phase: ACN / DW with 1% Phosphoric acid = 48 / 52

[0262] Flow rate: 1.0 ml / min

[0263] Wavelength: 200 nm

[0264] Column: Newcrom R1 (100*3.2 mm, 3 um)

[0265] Column temperature: 35℃

[0266] Injection volume: 30 ul

[0267] The test results are as shown in Fig. 25 and Table 1 below:

[0268] DHT adsorption amount (ug / mg MOF)PCN2235.194MOF5254.963UIO660.589MOF8080.295UIO676.142MIL88NH23.027

[0269] It was confirmed that all of the metal-organic frameworks of the present invention exhibit a DHT adsorption effect. However, it was confirmed that the DHT adsorption effect of the metal-organic frameworks varies depending on the specific surface area measured in Experimental Example 1. That is, it was confirmed that the larger the specific surface area of ​​the metal-organic framework, the better the DHT adsorption effect.

[0270] Preparation Example 2

[0271] Synthesis of novel organometallic frameworks

[0272] UIO67-ABA synthesis method

[0273] The synthesized UIO67 powder was subjected to removing residual solution from within the pores for 8 hours under a vacuum at 150°C. The powder from which the residual solution had been removed was mixed with ABA (3-Aminobenzyl alcohol) at a molar ratio of 1:50 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was dried at 80°C to obtain the powder.

[0274] UIO67-ABZ Synthesis Method

[0275] The residual solution within the pores of the synthesized UIO67 powder was removed by vacuuming at 150°C for 8 hours. ABZ (3,4-Diaminotoluene) was dissolved in DMSO at a concentration of 215 mg / ml. The residual solution-removed UIO67 and ABZ were mixed at a molar ratio of 1:30 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was obtained by drying at 80°C.

[0276] UIO67-AIA synthesis method

[0277] The residual solution within the pores of the synthesized UIO67 powder was removed by vacuuming at 150°C for 8 hours. AIA (5-Aminoisophthalic acid) was dissolved in DMSO at a concentration of 51 mg / ml. The residual solution-removed UIO67 and ABZ were mixed in a molar ratio of 1:20 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was obtained by drying at 80°C.

[0278] UIO67-ALA synthesis method

[0279] The residual solution within the pores of the synthesized UIO67 powder was removed by vacuuming at 150°C for 8 hours. ALA (5-aminolevulinic acid) was dissolved in DMSO at a concentration of 59 mg / ml. The UIO67 with the residual solution removed and ALA were mixed in a molar ratio of 1:5 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was obtained by drying at 80°C.

[0280] UIO67-AP synthesis method

[0281] The residual solution within the pores of the synthesized UIO67 powder was removed by vacuuming at 150°C for 8 hours. AP (2-aminopyrazine) was dissolved in DMSO at a concentration of 50 mg / ml. The residual solution-removed UIO67 and AP were mixed in a molar ratio of 1:15 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was obtained by drying at 80°C.

[0282] UIO67-APD Synthesis Method

[0283] The residual solution within the pores of the synthesized UIO67 powder was removed by vacuuming at 150°C for 8 hours. APD (2-Aminopyridine) was dissolved in DMSO at a concentration of 50 mg / ml. The residual solution-removed UIO67 and APD were mixed in a molar ratio of 1:15 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was obtained by drying at 80°C.

[0284] UIO67-DAT synthesis method

[0285] The synthesized UIO67 powder was subjected to removing residual solution from within the pores for 8 hours under a vacuum at 150°C. The powder from which the residual solution had been removed was mixed with DAT (3,4-Diaminotoluene) at a molar ratio of 1:50 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was dried at 80°C to obtain the powder.

[0286] UIO67-LS synthesis method

[0287] The residual solution within the pores of the synthesized UIO67 powder was removed by vacuuming at 150°C for 8 hours. An LS solution with a concentration of 100 mg / ml was prepared using ethanol. UIO67 was suspended in 3 ml of the LS solution such that the molar ratio of the residual-removed UIO67 to LS was 1:25, and the suspension was left at room temperature for 16 hours. The synthesized particles were washed three times each using ethanol. The powder was obtained by drying at 80°C.

[0288] UIO67-MB synthesis method

[0289] The synthesized UIO67 powder was subjected to removing residual solution from within the pores for 8 hours under a vacuum at 150°C. The UIO67 from which the residual solution had been removed and MB (2-methylbutylamine) were mixed at a molar ratio of 1:25 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was dried at 80°C.

[0290] UIO67-MN synthesis method

[0291] The synthesized UIO67 powder was subjected to removing residual solution from within the pores for 8 hours under a vacuum at 150°C. The UIO67 from which the residual solution had been removed and MN (2-Methoxy-4-nitroaniline) were mixed in a molar ratio of 1:5 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was dried at 80°C.

[0292] UIO67-MNA synthesis method

[0293] The synthesized UIO67 powder was subjected to removing residual solution from within the pores for 8 hours under a vacuum at 150°C. The UIO67 from which the residual solution had been removed and MNA (4-Methyl-3-nitroaniline) were mixed in a molar ratio of 1:5 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was dried at 80°C.

[0294] UIO67-PTA Synthesis Method

[0295] The synthesized UIO67 powder was subjected to removing residual solution from within the pores for 8 hours under a vacuum at 150°C. The UIO67 from which the residual solution had been removed was mixed with PTA (p-toluamide) in a molar ratio of 1:5 and suspended in 50 ml of toluene. The solution was placed in a round flask, connected to a reflux condenser, and stirred at 100°C for 6 hours. The synthesized particles were washed three times each with toluene and ethanol, respectively, and an ethanol substitution process was carried out for 3 days. After removing the ethanol, the powder was dried at 80°C.

[0296] UIO67-GAB Synthesis Method

[0297] The synthesized UIO67 powder was subjected to removing residual solution from within the pores for 8 hours in a vacuum environment at 150°C. A GAB (γ-Aminobutyric acid) solution with a concentration of 9 mg / ml was prepared using methanol. UIO67 was suspended in 8 ml of the GAB solution such that the molar ratio of the UIO67 with the removed residual solution to GAB was 1:5. Subsequently, the mixture was left at room temperature for 16 hours. The synthesized particles were washed three times each with ethanol. After removing the ethanol, the powder was obtained by drying at 80°C.

[0298] Experimental Example 4

[0299] Synthesis result analysis

[0300] To measure using a Scanning Electron Microscope (SEM), a powder sample was placed in a 2 mg to 3 mg Eppen tube, 100 µl of ethanol was added, and bath sonification was performed. Subsequently, 10 µl was spot-dried onto a silicon wafer and dried in an 80°C oven. The silicon wafer with the dried sample was then attached to the SEM mount using carbon tape and transferred to the SEM instrument to measure images (Company: Zeiss / Model: ULTRA PLUS).

[0301] Next, for X-ray diffraction (XRD) measurement, the powder sample was carefully placed on the XRD sample holder and compressed by pressing it with a glass slide glass with appropriate force. Afterward, all powder scattered around the sample holder was carefully removed, the sample holder was transferred to the equipment and set up, and measurements were performed in the range of 2°C to 30°C (Company: Bruker / Model: D2 phaser).

[0302] Next, for N2 adsorption isotherms and BET specific surface area-pore measurements, approximately 40 mg of a completely dried sample was prepared and carefully placed into a glass sampler using a glass funnel. All powder adhering to the area around the glass tube and the sample container at the bottom was removed. Subsequently, the top filter cap was attached, and degassing was performed in a pretreatment apparatus under vacuum and heat treatment at 120°C for 12 hours. The weight of the pretreated sample was measured using a microbalance, and the weight of the intact sample was calculated by subtracting the weight of the previously measured empty cell. The glass sampler was mounted on the N2 adsorption-desorption apparatus, and measurements were performed (Company Name: MICROTAAC / Model Name: BELSORP MINI X).

[0303] Scanning electron microscopy observation results for the above UIO67-ABA are shown in Fig. 26. In addition, X-ray diffraction analysis results are shown in Fig. 27, confirming that the prepared particles were synthesized with the crystal structure of UIO67-ABA. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 28. The specific surface area of ​​the UIO67-ABA particles analyzed through this is 2736.1 m². 2 / g is.

[0304] Scanning electron microscopy observation results for the above UIO67-ABZ are shown in Fig. 29. In addition, X-ray diffraction analysis results are shown in Fig. 30, confirming that the prepared particles were synthesized with the crystal structure of UIO67-ABZ. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 31. The specific surface area of ​​the UIO67-ABZ particles analyzed through this is 1581 m². 2 / g is.

[0305] Scanning electron microscopy observation results for the above UIO67-AIA are shown in Fig. 32. In addition, X-ray diffraction analysis results are shown in Fig. 33, confirming that the prepared particles were synthesized with the crystal structure of UIO67-AIA. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 34. The specific surface area of ​​the UIO67-AIA particles analyzed through this is 1134 m². 2 / g is.

[0306] Scanning electron microscopy observation results for the above UIO67-ALA are shown in Fig. 35. In addition, X-ray diffraction analysis results are shown in Fig. 36, confirming that the prepared particles were synthesized with the crystal structure of UIO67-ALA. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 37. The specific surface area of ​​the UIO67-ALA particles analyzed through this is 1167 m². 2 / g is.

[0307] Scanning electron microscope (SEM) observation results for the above UIO67-AP are shown in Fig. 38. In addition, X-ray diffraction analysis results are shown in Fig. 39, confirming that the prepared particles were synthesized with the crystal structure of UIO67-AP. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 40. The specific surface area of ​​the UIO67-AP particles analyzed through this is 3216.3 m². 2 / g is.

[0308] Scanning electron microscope (SEM) observation results for the above UIO67-APD are shown in Fig. 41. In addition, X-ray diffraction analysis results are shown in Fig. 42, confirming that the prepared particles were synthesized with the crystal structure of UIO67-APD. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 43. The specific surface area of ​​the UIO67-APD particles analyzed through this is 1750.5 m². 2 / g is.

[0309] Scanning electron microscope (SEM) observation results for the above UIO67-DAT are shown in Fig. 44. In addition, X-ray diffraction analysis results are shown in Fig. 45, confirming that the prepared particles were synthesized with the crystal structure of UIO67-DAT. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 46. The specific surface area of ​​the UIO67-DAT particles analyzed through this is 2756.3 m². 2 / g is.

[0310] Scanning electron microscope (SEM) observation results for the above UIO67-MB are shown in Fig. 47. In addition, X-ray diffraction analysis results are shown in Fig. 48, confirming that the prepared particles were synthesized with the crystal structure of UIO67-MB. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 49. The specific surface area of ​​the UIO67-MB particles analyzed through this is 2541.5 m². 2 / g is.

[0311] Scanning electron microscope (SEM) observation results for the above UIO67-MN are shown in Fig. 50. In addition, X-ray diffraction analysis results are shown in Fig. 51, confirming that the prepared particles were synthesized with the crystal structure of UIO67-MN. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 52. The specific surface area of ​​the UIO67-MN particles analyzed through these methods is 2457 m².2 / g is.

[0312] Scanning electron microscopy observation results for the above UIO67-MNA are shown in Fig. 53. In addition, X-ray diffraction analysis results are shown in Fig. 54, confirming that the prepared particles were synthesized with the crystal structure of UIO67-MNA. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 55. The specific surface area of ​​the UIO67-MNA particles analyzed through this is 3088.4 m². 2 / g is.

[0313] Scanning electron microscopy observation results for the above UIO67-PTA are shown in Fig. 56. In addition, X-ray diffraction analysis results are shown in Fig. 57, confirming that the prepared particles were synthesized with the crystal structure of UIO67-PTA. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 58. The specific surface area of ​​the UIO67-PTA particles analyzed through this is 2507.8 m². 2 / g is.

[0314] Scanning electron microscope (SEM) observation results for the above UIO67-GAB are shown in Fig. 59. In addition, X-ray diffraction analysis results are shown in Fig. 60, confirming that the prepared particles were synthesized with the crystal structure of UIO67-GAB. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 61. The specific surface area of ​​the UIO67-GAB particles analyzed through these methods is 1494.8 m². 2 / g is.

[0315] Scanning electron microscope (SEM) observation results for the above UIO67-LS are shown in Fig. 62. In addition, X-ray diffraction analysis results are shown in Fig. 63, confirming that the prepared particles were synthesized with the crystal structure of UIO67-LS. Furthermore, BET (Brunauer-Emmett-Teller) analysis results via N2 adsorption are shown in Fig. 64. The specific surface area of ​​the UIO67-LS particles analyzed through this is 164.1 m². 2 / g is.

[0316] Experimental Example 5

[0317] Cytotoxicity Assessment

[0318] L929 (mouse fibroblasts) were seeded into a 96-well plate at a density of 10,000 cells / well and cultured for 24 hours in a 37°C, 5% CO2 incubator. After 24 hours, the existing medium was removed from each well, and test solutions were prepared by suspending the particles to be tested in the medium at concentrations of 100, 50, 25, 10, 5, and 1 µg / ml. 100 µl of these solutions were then added to each well. After incubating for 24 hours in a 37°C, 5% CO2 incubator, the medium was removed and the cells were washed three times with PBS. 10% EZ-cytox medium was added to each well and incubated for 1 hour. Absorbance at 450 nm and 600 nm was measured using a microplate reader to compare cell viability with that of the control group.

[0319] The test results are as shown in FIGS. 65 to 77. Figure 65 shows the cytotoxicity results for UIO67-ABA, Figure 66 shows the cytotoxicity results for UIO67-ABZ, Figure 67 shows the cytotoxicity results for UIO67-AIA, Figure 68 shows the cytotoxicity results for UIO67-ALA, Figure 69 shows the cytotoxicity results for UIO67-AP, Figure 70 shows the cytotoxicity results for UIO67-APD, Figure 71 shows the cytotoxicity results for UIO67-DAT, Figure 72 shows the cytotoxicity results for UIO67-MB, Figure 73 shows the cytotoxicity results for UIO67-MN, Figure 74 shows the cytotoxicity results for UIO67-MNA, Figure 75 shows the cytotoxicity results for UIO67-PTA, Figure 76 shows the cytotoxicity results for UIO67-GAB, and Figure 77 shows the cytotoxicity results for UIO67-LS. According to the above test results, it was confirmed that more than 80% of cells survived across the entire concentration range for most MOFs, confirming that they are safe substances with no cytotoxicity.

[0320] Experimental Example 6

[0321] DHT adsorption experiment method

[0322] DHT (4,5a-Dihydrotestosterone) was prepared using EtOH to form a DHT solution with a concentration of 250 µg / ml. 25 mg of the MOF prepared according to the above preparation example was added to 4 ml of the above DHT solution. Afterward, it was left at room temperature for 24 hours. The supernatant was taken and centrifuged at 17,000 rpm for 5 minutes to remove particles, after which the DHT concentration of the supernatant was measured. After measuring the concentration of the DHT solution prepared above, the DHT concentration of the sample supernatant was subtracted to confirm the concentration and content of DHT adsorbed on the MOF.

[0323] HPLC measurement conditions

[0324] Mobile phase: ACN / DW with 1% Phosphoric acid = 48 / 52

[0325] Flow rate: 1.0 ml / min

[0326] Wavelength: 200 nm

[0327] Column: Newcrom R1 (100*3.2 mm, 3 um)

[0328] Column temperature: 35℃

[0329] Injection volume: 30 ul

[0330] The test results are as shown in Table 2 and Fig. 78 below:

[0331] DHT adsorption amount (ug DHT / mg MOF)UIO67-ABA19.13UIO67-ABZ20.86UIO67-AIA12.94UIO67-ALA19.73UIO67-AP22.09UIO67-APD7.82UIO 67-DAT15.47UIO67LS2.49UIO67-MB8.08UIO67-MN16.49UIO67-MNA22.54UIO67-PTA16.04UIO67-GAB13.47

[0332] It was confirmed that all of the metal-organic frameworks of the present invention exhibit a DHT adsorption effect. However, it was confirmed that the DHT adsorption effect of the metal-organic frameworks varies depending on the specific surface area measured in Experimental Example 4. That is, it was confirmed that the larger the specific surface area of ​​the metal-organic framework, the better the DHT adsorption effect.

[0333] Although preferred embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements by those skilled in the art using the basic concept of the present invention as defined in the following claims also fall within the scope of the present invention.

[0334] The present invention relates to a composition for the prevention or treatment of male pattern baldness by the adsorption and / or removal of dihydrotestosterone and the use thereof.

Claims

1. A metal-organic framework (MOF) comprising A composition for the prevention or treatment of male pattern baldness.

2. In Paragraph 1, The above metal-organic framework adsorbs and / or removes dihydrotestosterone A composition for the prevention or treatment of male pattern baldness.

3. In Paragraph 1, The above metal-organic framework has an average diameter of 500 nm or less. A composition for the prevention or treatment of male pattern baldness.

4. In Paragraph 1, The above metal-organic framework is a metal ion or metal cluster; and Comprising at least one organic ligand that forms a bond with the metal ion A composition for the prevention or treatment of male pattern baldness.

5. In Paragraph 4, The above metal cluster comprises a metal selected from the group consisting of Li, Na, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Re, Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Hg, Al, Ga, In, Tl, Si, Ge, Sn, Pb, As, Sb, and Bi. A composition for the prevention or treatment of male pattern baldness.

6. In Paragraph 4, 상기 금속 이온은 Li + In + , Mg 2+ , Ca 2+ Mr. 2+ , Ba 2+ , Sc 3+ Y 3+ Ti 4+ Zr 4+ , Hf 4+ V 4+ V 3+ V 2+ , Nb 3+ Ta 3+ Cr 3+ Mo 3+ W 3+ , Mn 3+ , Mn 2+ Re 3+ Re 2+ , Faith 3+ , Faith 2+ , Ru 3+ , Ru 2+ , You 3+ , You 2+ Co 3+ Co 2+ Rh 2+ Rh + Go 3+ Go 2+ Go + Ni 2+ Ni + , Pd 2+ , Pd + , PT 2+ , PT + , Cu 2+ , Cu + , Ag + Au + Zn 2+ CD 2+ Hg 2+ Al 3+ Ga 3+ In 3+ , Tl 3+ Yes 4+ Yes 2+ , Ge 4+ , Ge 2+ , Sn 4+ , Sn 2+ , Pb 4+ , Pb 2+ , As 5+ , As 3+ , As + , Sb 5+ , Sb 3+ , Sb + , Bi 5+ , Bi 3+ and Bi + Selected from a group consisting of A composition for the prevention or treatment of male pattern baldness.

7. In Paragraph 4, The above organic ligands are 1,3,5-benzenetricarboxylic acid, 4,4'-biphenyldicarboxilic acid, benzene-1,4-dicarboxylic acid, 9,10-anthracenedicarboxylic acid, biphenyl-3,3,5,5'-tetracarboxylic acid, biphenyl-3,4',5-tricarboxylic acid, 5-bromoisophthalic acid, and 5-cyano-1,3-benzenedicarboxylic acid. 2,2-diamino4,4'-stilbenedicarboxylic acid, 2,5-diaminoterephthalic acid, 1,1,2,2-tetra(4-carboxylphenyl)ethylene, 2,5-dihydroxyterephthalic acid, 2,2-dinitro-4,4-stilbenedicarboxylic acid, 5-ethynyl-1,3-benzenedicarboxylic acid, 2-hydroxyterephthalic acid, 2,6-naphthalenedicarboxylic acid, 1,2,4,5-tetrakis(4-carboxyphenyl)benzene, 4,4,4''-s-triazine-2,4,6-triyl-tribenzoic acid6-triyltribenzoic acid), 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, 1,3,5-tris(4-carboxy[1,1'-biphenyl]-4-yl)benzene, 1,3,5-tris(4-carboxyphenyl)benzene, 1,3,5-tris(4-carboxyphenyl)benzene, 1,3,5-triscarboxyphenylethynylbenzene, 2-methylimidazole and One or more selected from the group consisting of 2-aminoterephthalic acid, A composition for the prevention or treatment of male pattern baldness.

8. In Paragraph 1, A metal-organic framework (MOF) comprising a ligand compound further comprising the ligand compound represented by the following chemical formula 1 Composition for the prevention or treatment of male pattern baldness: [Chemical Formula 1] Here, n is an integer of 1 or 2, and EDP ​​refers to a group containing an electron pair donor atom, and L1 is selected from the group consisting of a substituted or unsubstituted alkyl group having 1 to 30 carbon atoms, a substituted or unsubstituted cycloalkyl group having 3 to 20 carbon atoms, a substituted or unsubstituted aralkyl group having 7 to 30 carbon atoms, a substituted or unsubstituted aryl group having 6 to 30 carbon atoms, a substituted or unsubstituted heteroaryl group having 1 to 60 carbon atoms, and a substituted or unsubstituted heteroarylalkyl group having 2 to 30 carbon atoms.

9. In Paragraph 8, The ligand compound represented by the above chemical formula 1 is a ligand compound represented by the following chemical formula 2 or chemical formula 3. Composition for the prevention or treatment of male pattern baldness: [Chemical Formula 2] [Chemical Formula 3] Here, The EDP is as defined in Paragraph 1, and m is an integer from 1 to 4, and p is an integer of 0 or 1, and L2 is selected from the group consisting of a single bond, a carbonyl group, a substituted or unsubstituted arylene group having 6 to 30 carbon atoms, a substituted or unsubstituted heteroarylene group having 1 to 30 carbon atoms, a substituted or unsubstituted alkylene group having 1 to 10 carbon atoms, a substituted or unsubstituted cycloalkylene group having 3 to 10 carbon atoms, a substituted or unsubstituted alkenylene group having 2 to 10 carbon atoms, a substituted or unsubstituted cycloalkenylene group having 3 to 10 carbon atoms, a substituted or unsubstituted heteroalkylene group having 1 to 10 carbon atoms, a substituted or unsubstituted heterocycloalkylene group having 2 to 10 carbon atoms, a substituted or unsubstituted heteroalkenylene group having 2 to 10 carbon atoms, and a substituted or unsubstituted heterocycloalkenylene group having 2 to 10 carbon atoms. X1 and X2 are identical or different from each other, and each is independently N or C(R3), and R1 to R3 are identical or different from one another and each independently hydrogen, deuterium, cyano group, nitro group, halogen group, hydroxyl group, substituted or unsubstituted C1 to C4 alkylthio group, substituted or unsubstituted C1 to C30 alkyl group, substituted or unsubstituted C3 to C20 cycloalkyl group, substituted or unsubstituted C2 to C30 alkenyl group, substituted or unsubstituted C2 to C24 alkynyl group, substituted or unsubstituted C7 to C30 aralkyl group, substituted or unsubstituted C6 to C30 aryl group, substituted or unsubstituted C1 to C60 heteroaryl group, substituted or unsubstituted C2 to C30 heteroarylalkyl group, substituted or unsubstituted C1 to C30 alkoxy group, substituted or unsubstituted C1 to C30 of It is selected from the group consisting of an alkylamino group, a substituted or unsubstituted arylamino group having 6 to 30 carbon atoms, a substituted or unsubstituted aralkylamino group having 7 to 30 carbon atoms, a substituted or unsubstituted heteroarylamino group having 1 to 24 carbon atoms, a substituted or unsubstituted alkylsilyl group having 1 to 30 carbon atoms, a substituted or unsubstituted arylsilyl group having 6 to 30 carbon atoms, and a substituted or unsubstituted aryloxy group having 6 to 30 carbon atoms.

10. A composition for the prevention or treatment of male pattern baldness according to any one of claims 1 to 9 Cosmetic composition.

11. In Paragraph 10, The above cosmetic composition is used by applying it to the hair and / or scalp, and The metal-organic framework (MOF) included in the above cosmetic composition penetrates the hair follicle to adsorb and / or remove dihydrotestosterone Cosmetic composition.

12. In Paragraph 10, The above-mentioned metal-organic framework within the hair follicle adsorbs and / or removes dihydrotestosterone for more than 24 hours Cosmetic composition.

13. In Paragraph 10, The metal-organic framework that adsorbs and / or removes dihydrotestosterone within the hair follicle is expelled externally as hair grows. Cosmetic composition.

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