CN101757013B - Hair-growing agent composition - Google Patents
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- CN101757013B CN101757013B CN2009101762529A CN200910176252A CN101757013B CN 101757013 B CN101757013 B CN 101757013B CN 2009101762529 A CN2009101762529 A CN 2009101762529A CN 200910176252 A CN200910176252 A CN 200910176252A CN 101757013 B CN101757013 B CN 101757013B
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Abstract
The invention provides a hair-growing agent composition, which is capable of treating exiguous human hair, calvities occurring in females due to lowering of the estrogen concentration along with the aging by using soybean isoflavones aglycone and 6-benzyl amino purine at the same time, and has great calvities prevention effect while having hair-growing effect. The invention provides a hair-growing agent composition containing soybean isoflavones aglycone and 6-benzyl amino purine. An ideal condition is that the soybean isoflavones aglycone is any one from the daidzin, genistin, and the mol ratio between soybean isoflavones aglycone (A) and 6-benzyl amino purine is 1:1000000 - 1000:1 or the like.
Description
Technical field
The present invention relates to a kind of hair-growing agent composition, it has the Effect of promoting growth of excellent keratinization of epidermis cell and the expression facilitation effect of BMP-2 gene.
Background technology
All the time, people expect to provide a kind of and send out an agent for sharply reduce effectively the educating of hair problem that causes due to female estrogen.Soybean isoflavone is known by the people as having the compound of female estrogen sample effect, and wherein, known malonyl soybean isoflavone aglycones has the effect (referring to Patent Document 1) that makes the keratinization of epidermis cell proliferation.But above-mentioned malonyl soybean isoflavone aglycones is heated and easily decomposes, and has the problem of malonyl hydrolysis in long preservation.
On the other hand, in the people's of baldness scalp, as the protein that reduces known BMP-2 (with reference to non-patent literature 1) arranged.Therefore, as the compound that promotes that BMP-2 produces, the applicant has reported 6-benzylaminopurine (with reference to non-patent literature 2).Described 6-benzylaminopurine is the compound (referring to Patent Document 2) that outbreak use is educated in known having, in the women of baldness, carried out mixing the confirmation test of educating the effectiveness of sending out agent of 6-benzylaminopurine, can see the slight effect of improving, but still can not obtain to improve significantly effect (with reference to non-patent literature 3).
Therefore, present situation be people strongly need to provide early a kind of can be for sharply reduce the effective hair-growing agent composition of the hair problem that causes due to female estrogen.
[patent document 1] Japanese patent laid-open 9-59166 communique
[patent document 2] Japanese patent laid-open 5-320028 communique
[non-patent literature 1] Journal of dermatological science (2004) 36,25-32
The basic aging association of [non-patent literature 2] the 26th Japan emerald green river occasion in 2004 are capable etc.
[non-patent literature 3] skin, the 40th volume, No. 4, in August, 1998, three islands are rich etc.
Summary of the invention
The present invention is to solve the above-mentioned variety of issue that existed and to reach following purpose as problem in the past.Namely, the objective of the invention is, a kind of hair-growing agent composition is provided, by also using soybean isoflavone aglycones and 6-benzylaminopurine, for occur in the women that estrogen concentrations reduces due to age growth send out rare, alopecia, educate the Anti-hair loss effect that also has excellence when sending out effect having.
For solving above-mentioned problem, the present inventor is through research with keen determination repeatedly, found that, by by and with (A) soybean isoflavone aglycones and (B) effect that multiplies each other of 6-benzylaminopurine, can obtain the expression facilitation effect of excellent keratinization of epidermis cel l proliferation and significant BMP-2 gene, for estrogenic minimizing cause send out rare, alopecia, be improved as thick, solid hair, have simultaneously anti-loss effect.
The present invention is that the inventor completes based on above-mentioned knowledge, and the means that solve above-mentioned problem are as described below.That is,
(1) a kind of hair-growing agent composition, is characterized in that, contains soybean isoflavone aglycones and 6-benzylaminopurine and consist of.
(2) according to above-mentioned (1) described hair-growing agent composition, described soybean isoflavone aglycones be in daidzin, genistin at least any.
(3) according to the described hair-growing agent composition of any one in above-mentioned (1) or (2), the mol ratio of described soybean isoflavone aglycones (A) and 6-benzylaminopurine (B) (A: B) be 1: 1000000～1000: 1.
(4) a kind of keratinization of epidermis cell proliferation promotes compositions, it is characterized in that, contains soybean isoflavone aglycones and 6-benzylaminopurine and consists of.
(5) a kind of expression of BMP-2 gene promotes to it is characterized in that compositions, contains soybean isoflavone aglycones and 6-benzylaminopurine and consists of.
By the present invention, can solve variety of issue in the past, a kind of hair-growing agent composition can be provided, by also using soybean isoflavone aglycones and 6-benzylaminopurine, for occur in the women that estrogen concentrations reduces due to age growth send out rare, alopecia, educate the Anti-hair loss effect that also has excellence when sending out effect having.
Description of drawings
[Fig. 1] Fig. 1 is the figure that shows the result that the proliferation activity of the keratinization of epidermis cell of embodiment 1 is estimated.
[Fig. 2] Fig. 2 is the figure of result that estimates the proliferation activity of keratinization of epidermis cell when show changing the mol ratio of daidzin and 6-benzylaminopurine in embodiment 2.
[Fig. 3] Fig. 3 is the figure of result that estimates the proliferation activity of keratinization of epidermis cell when show changing the mol ratio of genistin and 6-benzylaminopurine in embodiment 3.
[Fig. 4] Fig. 4 is the figure of result of the gene expression facilitation effect of the erss that causes of 6-benzylaminopurine in Evaluation operation example 4 and daidzin and BMP-2.
The specific embodiment
Hair-growing agent composition of the present invention contains soybean isoflavone aglycones (A) and 6-benzylaminopurine (B), can also contain other composition as required.
In the present invention, send out effect owing to educating by the Effect of promoting growth performance of keratinization of epidermis cell, therefore sometimes also hair-growing agent composition of the present invention is called " the keratinization of epidermis cell proliferation promotes compositions ", again, send out effect owing to educating by the expression facilitation performance of BMP-2 gene, therefore sometimes also referred to as " expression of BMP-2 gene promotes compositions ".
＜(A) soybean isoflavone aglycones 〉
Osajin belongs to flavonoid, has confirmed to have antioxidation, estrogen-like effects.
Measure the osajin of Semen sojae atricolor and confirmed to exist 12 kinds of isoflavone.it is daidzin (Daidzin) that these 12 kinds of isoflavone have the glycosides of (1) daidzein (Daidzein) and (2) daidzein, (3) acetylate of daidzin is Acetyldaidzin, (4) the malonyl compound of daidzin is malonyl-daidzin, (5) glycosides of genistein (Genistein) and (6) genistein is genistin (Genistin), (7) acetylate of genistin is Acetylgenistin 6''-O-Acetylgenistin, (8) the malonyl compound of genistin is malonyl-genistin, (9) Glycitein (Glycitein), (10) glycosides of Glycitein is glycitin (Glycitin), (11) acetylate of glycitin (Glycitin) is the acetyl group glycitin, (12) the malonyl compound of glycitin is the malonyl glycitin.
In dry Semen sojae atricolor; in these 12 kinds of osajins; these 4 kinds of malonyl-daidzins shown in malonyl-genistin shown in daidzin shown in genistin shown in following structural formula (I), following structural formula (II), following structural formula (III) and following structural formula (IV) account for major part; from the propagation facilitation effect this point of keratinization of epidermis cell, daidzin, genistin are especially desirable.
＜structural formula (I) 〉
Genistin (Genistin) (molecular weight: 432.3)
[changing 2]
＜structural formula (II) 〉
Daidzin (Daidzin) (molecular weight: 416.38)
[changing 3]
＜structural formula (III) 〉
Malonyl-genistin (malonyl-genistin) (molecular weight: 432.38)
[changing 4]
＜structural formula (IV) 〉
Malonyl-daidzin (malonyl-daidzin) (molecular weight: 432.38)
[changing 5]
As above-mentioned soybean isoflavone aglycones, both can use the soybean isoflavone aglycones of suitable preparation, also can use commercially available product.
As above-mentioned soybean isoflavone aglycones, be not particularly limited, can selection suitable to purpose, as soybean isoflavone aglycones, filter or centrifugalize after can using water or ethanol equal solvent to extract from Semen sojae atricolor, as required refining the and product that makes.
Compound method as above-mentioned soybean isoflavone aglycones has: for example, add entry in Semen sojae atricolor, filter after dipping, then, use water hot extraction's residue, with the liquid cools to 30 after the water hot extraction～38 ℃, then, remove insoluble matter, obtain thus containing the Semen sojae atricolor extract of isoflavone aglycone.
As separate the method for soybean isoflavone aglycones from the Semen sojae atricolor extract that obtains, can exemplify the method for the use adsorbent of putting down in writing in Japanese patent laid-open 11-255792 communique.That is, make soybean extraction liquid by having filled the pillar of the adsorbents such as ダ イ ヤ イ オ Application HP-20 (Mitsubishi chemical Co., Ltd), adsorb thus soybean isoflavone aglycones.Then, will be adsorbed on soybean isoflavone aglycones stripping on adsorbent with the different aqueous solution of concentration of alcohol.The solution decompression that obtains is concentrated, lyophilization, can obtain thus the dried powder of soybean isoflavone aglycones.
Commercially available product as above-mentioned soybean isoflavone aglycones; be not particularly limited; can selection suitable to purpose; for example, daidzin (Off ジ Star コ Co., Ltd. system), genistin (Off ジ Star コ Co., Ltd. system), malonyl-daidzin (with the pure medicine of light Co., Ltd. system), malonyl-genistin (with the pure medicine of light Co., Ltd. system) etc.Again, can exemplify as the extract that contains soybean isoflavone aglycones that extracts from Semen sojae atricolor, " Off ラ ボ ス テ ロ Application SE " (ball Off ア Le コ ス Co., Ltd. system, daidzin content 0.07w/v%～0.15w/v%, genistin content 0.01w/v%～0.03w/v%) etc.
＜(B) 6-benzylaminopurine 〉
Above-mentioned 6-benzylaminopurine is that the molecular weight shown in following structural formula is 225.26 white crystalline powder, and another name is also referred to as 6-benzyladenine.
[changing 1]
Above-mentioned 6-benzylaminopurine turns to purpose with the effect that prevents skin aging and the outer cell-activating that is used for scalp, be used as educate send out an agent (with reference to Japanese patent laid-open 5-320028 communique, Unexamined Patent 7-233037 communique), cosmetics for skin (with reference to No. the 4th, " skin " the 40th volume, P407～413,1998 year Augusts, three islands rich etc.).
Above-mentioned 6-benzylaminopurine both can use suitable synthetic, also can use commercially available product.
Be not particularly limited as above-mentioned synthetic method, can selection suitable to purpose, for example, the synthetic method of putting down in writing in Japanese Patent Laid-Open 2005-35903 communique or refining method etc. from natural product.
Can exemplify 6-benzylaminopurine (three province Pharmaceutical Co., Ltd systems, molecular weight=225.26) etc. as above-mentioned commercially available product.
Mechanism is sent out in educating of 6-benzylaminopurine
The applicant has reported that in cell culture experiments 6-benzylaminopurine promotes to be called as the generation of the protein of BMP-2 (with reference to the 26th basic aging association of Japan emerald green river occasion in 2004 capable etc.).Again, the applicant's report, BMP-2 is a kind of protein, the generation of BMP-2 can reduce in the people's of baldness scalp cells, thereby the 6-benzylaminopurine by excellent the educating of generation performance that promotes BMP-2 send out an effect (Journal of dermatological science (2004) 36,25-32).
In hair-growing agent composition, the combined amount of soybean isoflavone aglycones and 6-benzylaminopurine is preferably, (A) soybean isoflavone aglycones is 0.000002 quality %～4 quality %, (B) the 6-benzylaminopurine is 0.02 quality %～2 quality %, wherein, being more preferably (A) soybean isoflavone aglycones is 0.000002 quality %～0.2 quality %, and (B) the 6-benzylaminopurine is 0.1 quality %～0.5 quality %.
Mol ratio (the A: B) be preferably 1: 1000000～1000: 1, be more preferably 1: 1000000～10: 1, then be 1: 1000000～1: 1 well of described (A) soybean isoflavone aglycones and described (B) 6-benzylaminopurine.In this scope, can obtain the propagation facilitation effect of excellent keratinization of epidermis cell.
Skin surface is covered by epidermis, and the main cell that consists of epidermis is the cell that is called as the keratinization of epidermis cell.The keratinization of epidermis cell is widely used as the material of Dermatology research, simultaneously, also is widely used as the model of hair scientific research.This be because from the words hair of Dermatology be skin the accessory organ, be the part of skin.Hair-growing agent composition of the present invention also promotes the Keratinocytic propagation of hair when promoting the keratinization of epidermis cell proliferation, therefore, form thick root of hair, can promote to educate and send out, simultaneously, can be anti-loss.
Hair-growing agent composition of the present invention contains (A) soybean isoflavone aglycones and (B) 6-benzylaminopurine and consisting of, directly be used in the words on scalp, in hair cycle, by being suppressed to long-term movement to resting stage, more extending the growth stage, thereby when effect is sent out in stronger educating, brought into play more excellent Anti-hair loss effect.In order further to improve such effect that multiplies each other, as required or according to application target, in the scope of not damaging purpose of the present invention and effect, can contain above-mentioned (A) soybean isoflavone aglycones and (B) any composition beyond the 6-benzylaminopurine in hair-growing agent composition of the present invention.
As above-mentioned any composition, be not particularly limited, can select arbitrarily as required, for example, water, ethanol, nonionic surfactant, amphoteric surfactant or other surfactant, cellulose family, vegetable oil, ester oil, keratin-lytic agent, macromolecule resin, UV absorbent, vitamins, vasodilation, cell vitalizing agent, amino acids, antiinflammatory, hyperfunction dose of skin function, coloring agent, spice etc.
As above-mentioned water, can give an example, Purified Water, distilled water, ion exchange water, pure water, ultra-pure water, deep seawater etc.
As above-mentioned cellulose family, can give an example, hydroxy methocel, hydroxypropyl cellulose, hydroxypropyl emthylcellulose etc.
As above-mentioned nonionic surfactant can give an example sorbitan aliphatic ester class (sorbitan monolaurate, sorbitan monoleate etc.), poly(ethylene oxide) hardened castor oil, poly(ethylene oxide) hardened castor oil monostearate or isostearate, fatty glyceride, polyglycerol fatty acid ester (single myristic acid ten glyceride, single myristic acid five glyceride) etc.
As above-mentioned esters, can give an example, polyol esters of fatty acids (polyol fatty acid ester of three-2 ethyl hexanoic acid glyceride, three isostearic acid trihydroxy methyl propanoic acid etc. etc.).
As above-mentioned vegetable oil, can give an example, Eucalyptus oil, safflower oil, Radix Oenotherae erythrosepalae oil, Jojoba wet goods.
As above-mentioned ester oil, can give an example, unsaturated fatty acids acid alkyl ester (ethyl oleate, linoleic acid isopropyl ester etc.), methyl myristate, isopropyl myristate etc.
As above-mentioned keratin-lytic agent, can give an example, salicylic acid, resorcinol etc.
As above-mentioned macromolecule resin, can exemplify amphiphilic polymers, cation property copolymer, anionic property polymer, nonionic polymer etc.
As above-mentioned UV absorbent, can exemplify octyl methoxycinnamate (Neo Heliopan AV), phenol, urocanic acid etc.
As the said vitamin class, can exemplify vitamin A, vitamin B, vitamin C, vitamin E, tocopheryl acetate etc.
As above-mentioned vasodilation, can exemplify carpronium Chloride, minoxidil (Minoxidil), cepharanthine (セ Off ア ラ Application チ Application) etc.
As above-mentioned cell vitalizing agent, can exemplify pentadecanoic acid glyceride, coleus extract (コ レ ウ ス エ キ ス), Radix Ginseng extract, adenosine (ア デ ノ シ Application) etc.
As above-mentioned amino acids, can exemplify glutamic acid, methionine, serine, glycine, cysteine, threonine etc.
As above-mentioned antiinflammatory, can exemplify enoxolone, glycyrrhizic acid dipotassium, Herba Rosmarini Officinalis extract, Folium Perillae (シ ソ) extract etc.
As hyperfunction dose of above-mentioned skin function, can exemplify D-panthenol, pantothenic acid alcohol ethylether etc.
(purposes)
Hair-growing agent composition of the present invention can according to well-established law, be used for hair conditioner, suppurative mastitis, surfactant, shampoo, pomade, lotion etc. with forms such as homogeneous solution, washing liquid, gels.Can be used as to have and educate the external preparation of sending out effect and use again.
(form)
Hair-growing agent composition of the present invention can adopt aerocolloidal form, at this moment, except mentioned component, can also contain the lower alcohols such as normal propyl alcohol or isopropyl alcohol, the imflammable gas such as butane, propane, iso-butane, liquefied petroleum gas, dimethyl ether, the compression such as nitrogen, oxygen, carbon dioxide, nitrous oxide gas gas.
Hair-growing agent composition of the present invention contains (A) composition soybean isoflavone aglycones and (B) composition 6-benzylaminopurine and consisting of, directly be used in the words on scalp, due to the effect that multiplies each other, promoted the propagation of hair cell, be improved as thick, solid hair, bring into play simultaneously anti-loss effect.
Embodiment
Below, embodiments of the invention are described, but do not limited by these embodiment.
The assay method of＜keratinization of epidermis cell-proliferation activity 〉
The assay method of keratinization of epidermis cell-proliferation activity is following to carry out.
Normal person's keratinization of epidermis cell adopts from 24 years old women's once cultivation and freezes product (Cascade Biologics company system, NHEK (B)).Again, culture medium adopts Humedia KG2 (Cangfu twist flax fibers and weave society's system).Be 4400 cells/well at 24 orifice plates (Sumitomo backlight Co., Ltd. system) upper seeding wheel, with it under 5% carbon dioxide, saturated steam, 37 ℃ of cultivations.Cultivate after 24 hours, draw culture fluid, add fresh Humedia KG2, add and estimate material, then cultivated 48 hours.After cultivation, add Alamar Blue (Invitrogen society system) and be 10% concentration, measure fluorescence (excite 544nm, measure 590nm), with it as initial measured value.Under 5% carbon dioxide, saturated steam, cultivate for 37 ℃ and again measure fluorescence (excite 544nm, measure 590nm) after 3 hours, the difference between this measured value and initial value is active as Alamar Blue.Substitute and estimate extract, the Alamar Blue activity during take employing ethanol is as 100, with the proliferation activity of the Alamar Blue activity of respectively estimating extract at this moment as the keratinization of epidermis cell.
(test example 1)
The evaluation of the cell-proliferation activity of keratinization of epidermis cell
Preparation contain respectively in daidzin, genistin, malonyl-daidzin, malonyl-genistin and 6-benzylaminopurine any one, concentration be 10ng/mL Humedia KG2 culture medium (after in the ethanol that soybean isoflavone aglycones or the 6-benzylaminopurine of 50 μ g is dissolved in 10mL, with the solution of ethanol dilution to 50 times as stock solution.Then, the stock solutions of 1/100th amounts of Humedia KG2 culture medium are added in the HumediaKG2 culture medium, preparation and get), estimate as mentioned above the cell-proliferation activity of keratinization of epidermis cell.
As a comparison, prepare the Humedia KG2 culture medium that contains any one in daidzin, genistin, malonyl-daidzin, malonyl-genistin and contain the 6-benzylaminopurine with 5ng/mL concentration with 5ng/mL concentration.That is, in the ethanol that soybean isoflavone aglycones or the 6-benzylaminopurine of 50 μ g is dissolved in 10mL after, with the solution of ethanol dilution to 50 times as stock solution.Then, with Humedia KG2 culture medium 1/200th the amount the soybean isoflavone aglycones stock solutions and 1/200th the amount 6-benzylaminopurine stock solutions add in the HumediaKG2 culture medium, the preparation and get.
Use the cell-proliferation activity of the culture medium evaluation keratinization of epidermis cell of these preparations.In contrast, the formulated contrast of ethanol for 1/100th amounts of adding Humedia KG2 culture medium, also carry out the evaluation of the cell-proliferation activity of keratinization of epidermis cell, the cell-proliferation activity when proliferation activity of contrast is a corpse or other object for laboratory examination and chemical testing that added separately at 1 o'clock than (cell-proliferation activity the during cell-proliferation activity during a proliferation activity ratio=interpolation corpse or other object for laboratory examination and chemical testing/interpolation ethanol (contrast)), is shown in Fig. 1 as proliferation activity.
From the result of Fig. 1 as can be known, malonyl-daidzin, malonyl-genistin have respectively the proliferation activity of 3.7 times, 3.8 times, as Unexamined Patent 9-59166 puts down in writing, have confirmed the physiological activity of malonyl isoflavone aglycone.Although confirmed that also daidzin, genistin have respectively the proliferation activity of 1.5 times, 1.6 times, but by making up with the 6-benzylaminopurine, proliferation activity is respectively by activation to 12.3 times, 10.8 times, by and can confirm to have with soybean isoflavone aglycones and 6-benzylaminopurine the effect of multiplying each other.Again, although malonyl isoflavone aglycone and 6-benzylaminopurine and with also having confirmed the increase of proliferation activity, with respectively separately interpolation compare, there do not have to be significant poor.
(test example 2)
Keratinization of epidermis cell-proliferation activity when changing the mol ratio of daidzin and 6-benzylaminopurine
Preparation contains daidzin and 6-benzylaminopurine and the mol ratio of daidzin and 6-benzylaminopurine is modulated into Humedia KG2 culture medium from 0: 1 to 1: 0 with total amount 10ng/mL.
Then, according to the method evaluation keratinization of epidermis cell-proliferation activity identical with above-mentioned keratinization of epidermis cell-proliferation activity assay method.The results are shown in Fig. 2.
Can know from the result of Fig. 2 and find out, compared with adding separately respectively daidzin and 6-benzylaminopurine, by both are made up interpolation, can confirm that high keratinization of epidermis cell proliferation promotes active.What see keratinization of epidermis cell proliferation facilitation effect is daidzin: when the mol ratio of 6-benzylaminopurine is 1: 1000000～10000: 1, see extra high keratinization of epidermis cell-proliferation activity, it is desirable to 1: 1000000～1: 1 the time.
(test example 3)
Keratinization of epidermis cell-proliferation activity when changing the mol ratio of genistin and 6-benzylaminopurine
Preparation contains genistin and 6-benzylaminopurine and the mol ratio of genistin and 6-benzylaminopurine is modulated into Humedia KG2 culture medium from 0: 1 to 1: 0 with total amount 10ng/mL.
Then, according to the method evaluation keratinization of epidermis cell-proliferation activity identical with above-mentioned keratinization of epidermis cell-proliferation activity assay method.The results are shown in Fig. 3.
Can know from the result of Fig. 3 and find out, compared with adding separately respectively genistin and 6-benzylaminopurine, by both are made up interpolation, can confirm that high keratinization of epidermis cell proliferation promotes active.What see keratinization of epidermis cell proliferation facilitation effect is genistin: when the mol ratio of 6-benzylaminopurine is 1: 1000000～10: 1, see extra high keratinization of epidermis cell-proliferation activity be 1: 1000000～1: 1 the time.
(test example 4)
The gene expression facilitation effect validation test that 6-benzylaminopurine, daidzin cause
At 24 orifice plate upper seeding wheel keratinization of epidermis cells, make it become 3000 cells/cm
2, as culture medium, making every hole is 0.5mL to inject respectively HumediaKG2 (Cangfu twist flax fibers and weave society's system) in every hole, with it under 5% carbon dioxide, saturated steam, 37 ℃ of cultivations.On next day, prepare respectively (a) 6-benzylaminopurine 1 μ g/mL, (b) daidzin 1 μ g/mL or (c) daidzin 500ng/mL and the 6-benzylaminopurine 500ng/mL (solution of mol ratio (daidzin: the 6-benzylaminopurine)=1: 1.8) concentration with ethanol.
Add these in Humedia KG2 culture medium (ultimate density in culture medium is (a) daidzin 10ng/mL, (b) genistin 10ng/mL, (c) daidzin 5ng/mL and genistin 5ng/mL) to cultivate 1/100th of base unit weight.Cultivate the keratinization of epidermis cell after 20 hours in these culture medium, extract mRNA.The extraction Jing System of mRNA uses QIA shredder (QIAGEN company system), RNeasy Mini (QIAGEN company system).MRNA after refining is as the basis, uses the synthetic cDNA of RTase (TOYOBO company system).
CDNA after synthetic is as the basis, uses ExTaq HS (TaKaRa company system) to carry out PCR reaction (cultivating after 5 minutes the anti-ying of amplification of 30 circulations (94 ℃ of lower 30 seconds, the thaw temperature of primer lower 60 seconds, 72 ℃ lower 60 seconds) under 94 ℃).Carry out with this reactant liquor the electrophoresis that 1% agarose gel causes, relatively the gene expression of erss (ER-β), BMP-2 and GAPDH (contrast).Result is shown in Fig. 4.
From the result of Fig. 4 as can be known, when adding together daidzin and 6-benzylaminopurine in cell, the gene expression of erss and BMP-2 uprises with multiplying each other.
The effect that multiplies each other that the combination of 6-benzylaminopurine and daidzin or genistin causes
Up to now, the applicant has reported the keratinocyte for hair follicle, and BMP-2 has the cell proliferation facilitation effect (with reference to Journal of Dermatological Science (2004) 36,25-32).Again, the gene expression of also having reported BMP-2 promotes (basic aging association 29,25 (2005), FRAGRANCE Journal2005 December number) by erss, has known that erss promotes the growth of hair follicle by BMP-2.
But, as shown in test example 4, by also using soybean isoflavone aglycones and 6-benzylaminopurine, the gene expression of erss is by multiplicity ground promotion, this is a new discovery, accompany therewith, because the gene expression of BMP-2 is promoted, the propagation facilitation effect of the keratinization of epidermis cell shown in test example 1～3 occurs.
Therefore, contain (A) soybean isoflavone aglycones and (B) 6-benzylaminopurine and the hair-growing agent composition that consists of for cause less due to estrogen De Minus send out rare, alopecia, be improved as thick, solid hair, the while can be brought into play anti-loss effect.
(embodiment 1～9 and comparative example 1～5)
The preparation of hair-growing agent composition
Form according to the proportioning shown in following table 1, prepare hair-growing agent composition by well-established law.In addition, proportioning unit is quality %, total amount 100 quality %.
For each hair-growing agent composition that obtains, as follows, carry out the clinical test results about the therapeutic effect of male pattern alopecia disease.Result is shown in table 1.
＜to the clinical trial method of alopecia generalisata disease 〉
Take the female volunteers of 104 alopecia generalisata diseases as object, amount to 13 groups, 1 group of 8 random packet for tested medicament group and matched group.
Test is sooner or later from the beginning anteriorly to embrocate in right amount to head for 2 times every day.Throwing Yu Qi Inter is 4 months.
During off-test, (4 months) hair washing, cover the non-woven fabrics of 2 layers on bamboo basket, collects with it the hair that comes off in hair washing.Measure the radical of the hair of collecting, the radical of the hair that comes off in hair washing during with on-test compares.
Have one's hair wash 1 time on the 1st, carried out 3 continuously, the meansigma methods of the radical of 3 alopecias is used for judging, the radical of measuring alopecia by following formula changes.
Again, with reference to the photo finding, to the degree of improvement of the hair finding (variation of the matter of hair) that compares when the off-test and before on-test, judge according to following 5 grades of evaluations (significantly improvements, moderate improvement, slightly improve, do not change, deterioration).
(determinating reference)
The variation of alopecia radical
Alopecia radical during take on-test is 100%, the variation of the alopecia radical when calculating off-test.((the alopecia radical during the alopecia radical during off-test/on-test) * 100).
" improvement ": 90% of the not enough initial value of the alopecia radical during off-test
" constant ": the alopecia radical during off-test be worth in the early stage 90%～110% in
" deterioration ": not enough more than 111% of initial value of the alopecia radical during off-test
The variation of the matter of hair
" significantly improve ": 5 minutes (there is no soft hair, normalization)
" moderate improvement ": 4 minutes (soft hair has the sclerosis of certain degree)
" the slight improvement ": 3 minutes (slight hard the sending out of soft hair changed)
" constant ": 2 minutes (can't see the variation of the matter of hair fully)
" deterioration ": 1 minute (hair is softening)
[table 1-1]
[table 1-2]
[table 1-3]
*Daidzin (Off ジ Star コ Co., Ltd. system, solid constituent purity more than 99%, molecular weight=416.38)
*Genistin (Off ジ Star コ Co., Ltd. system, solid constituent purity more than 99%, molecular weight=432.38)
*6-benzylaminopurine (three province Pharmaceutical Co., Ltd systems, molecular weight=225.26)
*Polyethylene Glycol #300 (Lion Corporation's system)
*POE (30) POP (6)-decyl myristyl ether (daylight ケ ミ カ Le Co., Ltd. system)
(
*1): in embodiment 4 and comparative example 4, contain 0.1 quality % flavone sterone SE.Flavone sterone SE is the Semen sojae atricolor extract of ball Off ア Le コ ス Co., Ltd. system, contains daidzin 0.1 quality % in extract, genistin 0.02 quality %.
(
*2): mol ratio means arithmetic point 1 of the back numerical value that is rounded up
As can be known from the results of Table 1, contain effective ingredient ((A) composition and (B) composition), the embodiment within the scope of the present invention 1～9 of specified quantitative, all show excellent characteristic in Anti-hair loss effect and hair quality improve effect in advance.Again, do not use daidzin, the so refining thing of soybean isoflavone aglycones of genistin, comprise all these soybean isoflavone aglycones and (during flavone sterone SE (a ball Off ア Le コ ス Co., Ltd. system) (embodiment 4), distinguish that its pre-Anti-hair loss prevention and hair quality improve effect also excellent at interior Semen sojae atricolor extract but use.Again, embodiment 1～6 is more excellent than embodiment .7～8 effects, and is desirable especially.As the combined amount in hair-growing agent composition, from embodiment 1～8 as seen, when (A) composition is 0.000002 quality %～4 quality %, when (B) composition is 0.02 quality %～2 quality %, can see excellent effect again.
Wherein, (A) composition is 0.000002 quality %～0.2 quality %, (B) composition when being 0.1 quality %～0.5 quality %, can see excellent effect, and is desirable especially as the combined amount in hair-growing agent composition.
In contrast, distinguish that the comparative example 1～5 outside the scope of the invention does not all show excellent characteristic.Comparative example 1 be (A) composition and (B) composition all do not have, comparative example 2～4th only contains (A) composition, comparative example 5 is only to contain (B) composition, in these cases, can not bring into play as educating of the object of the invention and send out an effect, Anti-hair loss effect.
The concrete mix embodiment that the hair-growing agent composition of the present invention that then, will show excellent specific property in Anti-hair loss effect and hair growth promoting weight is used for actual product shows below.In addition, the hair-growing agent composition of following mix embodiment basis composition separately is according to the well-established law preparation of each dosage form.
To the hair-growing agent composition of the various dosage forms of following mix embodiment 1～5 (hair tonic preparation, educate and send out a spray, educate and send out hair conditioner, educate and send out a washing liquid), same with above-described embodiment 1～9 and comparative example 1～5, evaluation is educated and is sent out effect, result shows, in Anti-hair loss effect and hair growth promoting weight, all demonstrate the same excellent effect with embodiment 1～9.
(mix embodiment 1)
-educate send out an agent-
Flavone sterone SE
*: 0.1 quality % ... (A) composition
6-benzylaminopurine: 0.5 quality % ... (B) composition
Extract is made with extra care in the extraction of Coleus forskohlii Briq. (Coleus Forskohlii) root: 3.0 quality %
Fatty acid distribution of coconut oil sorbitan: 1.0 quality %
Sucrose myristate: 0.5 quality %
Lauryl dimethyl aminoacetic acid betanin: 0.5 quality %
Concentrated glycerin: 0.8 quality %
Myristic acid ten glycerol: 0.3 quality %
Biotin: 0.002 quality %
Succinic acid: 0.3 quality %
Acetic acid DL-alpha-tocopherol: 0.1 quality %
Spice: 0.5 quality %
95% ethanol: 50 quality %
Purified Water: surplus
Flavone sterone SE is the Semen sojae atricolor extract of ball Off ア Le コ ス Co., Ltd. system, contains daidzin 0.1 quality % in extract, genistin 0.02 quality %.
Mol ratio ((A) composition: (B) composition)=1: 7947 (mol ratio is a numerical value that rounds up of arithmetic point back)
(mix embodiment 2)
-educate send out a spray-
Daidzin: 0.0001 quality % ... (A) composition
6-benzylaminopurine: 0.1 quality % ... (B) composition
Extract is made with extra care in the extraction of Coleus forskohlii Briq. (Coleus Forskohlii) root: 1.0 quality %
Amphiphilic polymers (N-methacryloyl ethyl-N, N-dimethylammonium α-N-methyl carboxybetaine alkyl methacrylate copolymer): 0.2 quality %
Ethyl oleate: 1.0 quality %
Succinic acid: 0.3 quality %
Surfhope SE Cosme C 1216: 0.5 quality %
Lauryl dimethyl aminoacetic acid betanin: 0.5 quality %
Concentrated glycerin: 0.8 quality %
Single myristic acid ten glyceride: 0.3 quality %
MENTHOL: 0.1 quality %
Acetic acid DL-alpha-tocopherol: 0.1 quality %
Spice: 0.5 quality %
95% ethanol: 50 quality %
Purified Water: surplus
-dilution filling liquid-
Above-mentioned stock solution: 80 quality %
LPG:20 quality %
Mol ratio ((A) composition: (B) composition)=1: 1919 (mol ratio is a numerical value that rounds up of arithmetic point back)
(mix embodiment 3)
-educate send out hair conditioner-
Genistin: 0.00001 quality % ... (A) composition
6-benzylaminopurine: 0.05 quality % ... (B) composition
POE (8 moles) oleyl ether: 1.5 quality %
Glycerol: 0.3 quality %
MENTHOL: 0.1 quality %
Order cypress alcohol: 0.3 quality %
Methyl parahydroxybenzoate: 0.1 quality %
Spice: 0.3 quality %
95% ethanol: 50 quality %
Purified Water: surplus
Mol ratio ((A) composition: (B) composition)=1: 9242 (mol ratio is a numerical value that rounds up of arithmetic point back)
(mix embodiment 4)
-educate send out a surfactant-
Daidzin: 0.001 quality % ... (A) composition
6-benzylaminopurine: 0.5 quality % ... (B) composition
Natural Vitamin E: 0.5 quality %
Sucrose myristate: 0.5 quality %
POE (40) Semen Ricini oil that hardens: 0.5 quality %
Propylene glycol: 0.5 quality %
Citric acid: 0.1 quality %
MENTHOL: 0.1 quality %
Spice: appropriate
95% ethanol: 50 quality %
Purified Water: surplus
Mol ratio ((A) composition: (B) composition)=1: 9597 (mol ratio is a numerical value that rounds up of arithmetic point back)
(mix embodiment 5)
-educate send out hair conditioner-
Genistin: 0.001 quality % ... (A) composition
6-benzylaminopurine: 0.5 quality % ... (B) composition
Nicotiamide: 0.1 quality %
Piroctone olamine (Piroctone Olamine): 0.05 quality %
β-enoxolone: 0.01 quality %
Melissa plant extract: 3.0 quality %
POE (2 moles) oleyl ether: 0.5 quality %
PEG400: 2.0 quality %
MENTHOL: 0.1 quality %
Order cypress alcohol: 0.3 quality %
Spice: 0.3 quality %
95% ethanol: 50 quality %
Purified Water: surplus
Mol ratio ((A) composition: (B) composition)=1: 9242 (mol ratio is a numerical value that rounds up of arithmetic point back)
Utilizability on industry
Hair-growing agent composition of the present invention has excellent keratinization of epidermis cell proliferation facilitation and BMP-2 gene expression facilitation effect, particularly to sharply reduce the effective product of hair problem that causes due to female estrogen.For example, be widely used in to have and educate the hair conditioner of sending out effect, suppurative mastitis, surfactant, shampoo, pomade, lotion, external preparation etc.
Claims (2)
1. a hair-growing agent composition, is characterized in that, contain soybean isoflavone aglycones and 6-benzylaminopurine and consist of,
Described soybean isoflavone aglycones be in daidzin, genistin at least any,
The mol ratio of described soybean isoflavone aglycones (A) and 6-benzylaminopurine (B) is A: B is 1: 1000000～1000: 1.
2. hair-growing agent composition according to claim 1, (A) combined amount of soybean isoflavone aglycones is 0.000002 quality %～4 quality %, (B) combined amount of 6-benzylaminopurine is 0.02 quality %～2 quality %.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008331228A JP5363800B2 (en) | 2008-12-25 | 2008-12-25 | Hair restorer composition |
| JP2008-331228 | 2008-12-25 |
Publications (2)
| Publication Number | Publication Date |
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| CN101757013A CN101757013A (en) | 2010-06-30 |
| CN101757013B true CN101757013B (en) | 2013-06-19 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2009101762529A Expired - Fee Related CN101757013B (en) | 2008-12-25 | 2009-09-11 | Hair-growing agent composition |
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| Country | Link |
|---|---|
| JP (1) | JP5363800B2 (en) |
| KR (1) | KR101642986B1 (en) |
| CN (1) | CN101757013B (en) |
| HK (1) | HK1143772A1 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120136581A (en) * | 2011-06-09 | 2012-12-20 | (주)아모레퍼시픽 | Composition for prevention of losing hair or promotion of growing hair comprising bean extract |
| JP6026429B2 (en) * | 2011-12-19 | 2016-11-16 | 三省製薬株式会社 | Method for preparing hair restorer and composition thereof |
| JP7032852B2 (en) * | 2014-11-29 | 2022-03-09 | 共栄化学工業株式会社 | Hair cosmetics |
| JP6887675B2 (en) * | 2017-07-21 | 2021-06-16 | 三省製薬株式会社 | How to prepare a hair restorer and its solution |
| KR102054160B1 (en) * | 2017-10-10 | 2019-12-10 | 유씨엘 주식회사 | Cosmetic composition for preventing scalp aging and hair loss |
| CN110051555A (en) * | 2019-06-05 | 2019-07-26 | 南京迪维奥医药科技有限公司 | A kind of myristoyl pentapeptide -17 of generating hair and the composition of Wild soybean isoflavones |
| CN110302351A (en) * | 2019-08-15 | 2019-10-08 | 广州楚颜化妆品有限公司 | Anticreep oil-control educates hair and smears cream liquid and preparation method thereof |
| CN110538299B (en) * | 2019-09-09 | 2021-09-28 | 广州楚颜化妆品有限公司 | Hair-blacking anti-hair-loss oil-control anti-dandruff mite-removing external liquid medicine and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1401320A (en) * | 2001-10-26 | 2003-03-12 | 牛建昭 | Medicine for treating menopausal syndrome |
| JP2005035903A (en) * | 2003-07-16 | 2005-02-10 | Lion Corp | Hair-restoring and growing agent composition |
| CN1675211A (en) * | 2002-08-15 | 2005-09-28 | 西克拉塞尔有限公司 | New purine derivatives |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3302535B2 (en) * | 1995-08-17 | 2002-07-15 | キッコーマン株式会社 | Epithelial cell growth promoter |
| JPH1072321A (en) * | 1996-08-29 | 1998-03-17 | Sansho Seiyaku Co Ltd | Hair tonic |
| JP2005119996A (en) * | 2003-10-15 | 2005-05-12 | Sato Pharmaceutical Co Ltd | Hair-restoring agent |
| JP4469617B2 (en) * | 2004-01-16 | 2010-05-26 | 花王株式会社 | Hair restoration |
| JP2005200357A (en) * | 2004-01-16 | 2005-07-28 | Kanebo Cosmetics Inc | Hair-fostering cosmetic |
| JP2005281280A (en) * | 2004-03-31 | 2005-10-13 | Daicho Kikaku:Kk | Dermatologic preparation |
| KR100992565B1 (en) * | 2005-10-17 | 2010-11-08 | (주)아모레퍼시픽 | Topical preparations for hair growth |
| JP2007204426A (en) * | 2006-02-02 | 2007-08-16 | Kanebo Cosmetics Inc | Hair growth promoter |
| US20080175807A1 (en) | 2007-01-24 | 2008-07-24 | Fujifilm Corporation | Composition for hair |
-
2008
- 2008-12-25 JP JP2008331228A patent/JP5363800B2/en active Active
-
2009
- 2009-08-03 KR KR1020090071209A patent/KR101642986B1/en active IP Right Grant
- 2009-09-11 CN CN2009101762529A patent/CN101757013B/en not_active Expired - Fee Related
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1401320A (en) * | 2001-10-26 | 2003-03-12 | 牛建昭 | Medicine for treating menopausal syndrome |
| CN1675211A (en) * | 2002-08-15 | 2005-09-28 | 西克拉塞尔有限公司 | New purine derivatives |
| JP2005035903A (en) * | 2003-07-16 | 2005-02-10 | Lion Corp | Hair-restoring and growing agent composition |
Also Published As
| Publication number | Publication date |
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| KR20100075714A (en) | 2010-07-05 |
| JP2010150203A (en) | 2010-07-08 |
| KR101642986B1 (en) | 2016-07-26 |
| JP5363800B2 (en) | 2013-12-11 |
| CN101757013A (en) | 2010-06-30 |
| HK1143772A1 (en) | 2011-01-14 |
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