KR101948233B1 - Compositions for Preventing Hair Loss and Stimulating Hair Sprouting - Google Patents

Abstract

According to the present invention, provided is a composition for preventing hair loss and promoting hair growth, which includes 20-50 wt% of a compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof, 10-40 wt% of L-arginine, and 10-40 wt% of copper tripeptide-1 (GHK-Cu) based on the total weight of the composition. In chemical formula 1, R1 and R2 are the same or different and can be selected from the group consisting of hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, and halogen. The present invention is effective in alleviating general hair loss symptoms and is free from side effects.

Description

{Compositions for Preventing Hair Loss and Stimulating Hair Sprouting}

The present invention relates to hair loss prevention and hair growth promoting compositions.

The cause of hair loss from the scalp is caused by internal factors such as genetic constitution, male hormone action, mental stress in daily life, extrinsic factors such as accumulation of lipid peroxidation in the scalp, Are known. In recent years, not only male-type hair loss, but also hair loss in women, such as obesity hair loss is gradually spreading. Accordingly, many types of hair loss prevention and hair growth promoting agents have been developed and marketed to improve such hair loss phenomenon.

The most commonly known mechanism for improving hair loss symptoms is the mechanism by which male hormones are controlled to prevent hair loss and promote hair growth. However, most of the known technologies related thereto are not effective as hair loss prevention and hair growth promoting agent because they are insignificant or have a serious side effect and are safe and effective.

On the other hand, a variety of hair loss prevention and hair growth promoting agents including natural extracts are commercially available. These medicines have a therapeutic mechanism for improving blood circulation of the scalp by improving blood circulation and vasodilation by natural extracts, thereby improving hair loss symptoms. However, these drugs have little effect and thus fail to provide a satisfactory effect of improving hair loss symptoms.

Recently, it has been reported that the phenomenon of hair loss due to TGF-β is rapidly performed. Therefore, there is also developed a drug for alleviation of hair loss, which reduces the process of normal hair to progress to hair loss as a result of inducing inhibition of TGF-beta and consequently slows the hair loss phenomenon.

Korean Patent No. 10-1841042 discloses a pharmaceutical composition for improving or inhibiting hair loss, which is a side effect of cyclophosphamide, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient Lt; / RTI >

[Chemical Formula 1]

However, the pharmaceutical composition has disadvantages in that it is not effective in improving general hair loss symptoms, apart from improvement of hair loss symptoms due to side effects of cyclophosphamide. Therefore, there is a need for the development of effective drugs that can be used for general hair loss symptoms.

Korean Patent No. 10-1841042

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made keeping in mind the above problems occurring in the prior art, and an object of the present invention is to provide a composition for preventing hair loss and promoting hair growth, which is excellent in improving general hair loss symptoms and free from side effects.

The present invention, in order to achieve the above object,

Wherein the composition comprises 20 to 50% by weight of a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, 10 to 40% by weight of L-arginine, 10 to 40% by weight of copper tripeptide-1 % ≪ / RTI > by weight of a composition for promoting hair loss prevention and hair growth:

[Chemical Formula 1]

In Formula 1, R 1 and R 2 may be the same or different and may be selected from the group consisting of hydrogen, (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy and halogen.

In one embodiment of the invention, the composition comprises 5-20% by weight of pullulan, based on the total weight of the composition; 5 to 20% by weight of corn albumin; 5 to 20% by weight of boswelly acid; And 10 to 20% by weight of an extract of a mixture of a beard sprout flower and an acid beet pulp at a weight ratio of 0.5 to 1: 0.5 to 1.

In one embodiment of the present invention, the extract of the mixture obtained by mixing the whitish spore flower and the acidic beef at a weight ratio of 0.5: 0.5: 1 is extracted with 0.3 to 1.5 hours at the boiling temperature of ethanol using ethanol as an extraction solvent Lt; / RTI >

In one embodiment of the present invention, the composition for promoting hair loss prevention and hair growth may be a shampoo, a hair tonic, or the like as a cosmetic composition.

The hair loss prevention and hair growth promoting composition of the present invention provides an excellent effect for improving general hair loss symptoms without side effects.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a photograph showing the hair regrowth preventing effect of the hair loss prevention and hair growth promoting composition of the present invention confirmed by transdermal administration of a mouse.
FIG. 2 and FIG. 3 are photographs showing the effect of improving hair loss prevention when hair tonic is applied for 15 weeks as a hair loss prevention and hair growth promoting composition of the present invention.

Hereinafter, the present invention will be described with reference to preferred embodiments.

According to the present invention,

Wherein the composition comprises 20 to 50% by weight of a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, 10 to 40% by weight of L-arginine, 10 to 40% by weight of copper tripeptide-1 % ≪ / RTI > by weight of a composition for promoting hair loss and promoting hair growth,

[Chemical Formula 1]

In Formula 1, R 1 and R 2 may be the same or different and may be selected from the group consisting of hydrogen, (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy and halogen.

The compound of Formula 1 is known to have the effect of improving hair loss, which is a side effect of cyclophosphamide. However, there is a disadvantage in that the effect of improving general hair loss symptoms is not sufficient.

Therefore, the present inventors completed the composition of the present invention by combining the above-mentioned compound of Formula 1 with additional components capable of exhibiting a synergistic effect.

In one embodiment of the invention, the composition comprises 5-20% by weight of pullulan, based on the total weight of the composition; 5 to 20% by weight of corn albumin; 5 to 20% by weight of boswelly acid; And 10 to 20% by weight of an extract of a mixture of a beard sprout flower and an acid beet pulp at a weight ratio of 0.5 to 1: 0.5 to 1.

The exopolysaccharide (EPS pullulan) is an extracellular secretory polysaccharide produced by the fungus. It was first discovered by Bauer in 1938 and is known as a safe solution by many studies.

Pullulan is a water-soluble polysaccharide produced by the fungus Aureobasidium pullulans, which is linked to maltotriose units by α-1, 6 bonds. Fruiting bodies of mushrooms contain polysaccharides having a structure with β-1, 3 glycoside bonds as the main chain and a glucose residue attached at its C-6 position. Recently, β-glucan having such a structure has been found to have an action of inhibiting the proliferation of tumor cells, and attention has been paid.

The above-mentioned conalumin is also called ovotransferrin, which is a glycoprotein having a molecular weight of 76.6 kDa which is iron-bonded and occupies 12.6% of the egg white protein. The isoelectric point (pI) is 6.1. The second largest conglomerate of egg white protein has 686 amino acid residues and is composed of one glycan (N-acetylglucosamine) consisting of 15 disulfide bonds, 4 mannose and 8 N-acetylglucosamine ) Chain. Conalbumin is a thermally stable complex at pH 6 with two metal ions (Fe3 +, Al3 +, Cu2 +, Zn2 +, etc.). These complexes are reddish, colorless, yellow, and colorless, respectively. There are three types of ^conal albumin, one without Fe ³⁺ atom and one with two or more, and this iron binding ability plays an indirect role in preventing lipid oxidation. In addition, it is safe for thermal deformation and microbial contamination by bonding with metal ions, and plays an important role in processing and functional characteristics of egg white with various characteristics between iron-binding complex and non-iron-binding apoprotein.

The boswellic acid is obtained from the pale greenish juice which flows when the boswellia serrata tree is injured. Bosswellia Sereta is native to Africa, southern Arabia or India. Bosswelllic acid has traditionally been used for inflammation such as skin rashes and ulcers, respiratory diseases such as asthma, bronchitis and laryngitis, and it has been known to have medical effects such as arthritis.

Bosswelli acid is known to exhibit excellent inhibition of elastase activity and inhibition of glycosaminoglycan degradation.

The extract of the mixture obtained by mixing the above-mentioned whitish whiting flowers and the acidic beef at a weight ratio of 0.5: 1: 0.5 to 1 may be preferably used as an extraction solvent and extracted with ethanol at 0.3 to 1.5 hours at the boiling temperature of ethanol.

The beard sprout flower is a medicinal plant used as a herbal medicine in Oriental medicine and contains various physiologically active substances. The beard spore flower powder is called semi-mature, semi-irregular or rapid-hueing color. It is distributed in the southern part of central Korea and Jeju-do, and it lives in ditches, streams and wetlands of rice paddies. Beard flies have traditionally been used as medicines for the treatment of asthma, dyspnea, pertussis, malignant swelling, eczema and traumatic hemorrhage.

The mountain beetle is a vine extending bush root, also called a new sand vine (Menispermum dahuricum DC.). It is known to contain alkaloids, taurine, and terenadrine in roots and stems (Yakugawa Zasshi 1970). In addition, synomenin and taurine are known to have antipruritic effects and are also effective against hypertension and anti-inflammatory actions. Acta Med Okayama (1976) .

In one embodiment of the present invention, the composition for promoting hair loss prevention and hair growth may be a shampoo, a hair tonic, or the like as a cosmetic composition.

Hereinafter, the present invention will be described in more detail by way of examples. However, the following examples are intended to further illustrate the present invention, and the scope of the present invention is not limited by the following examples. The following examples can be appropriately modified and changed by those skilled in the art within the scope of the present invention.

Production Example 1: Production of beard sprout flower and mountain beet roots extract

500 g each of dried beard spiny flowers and mountain hulls were placed in a heating vessel, and 2 L of ethanol was added as an extraction solvent and heated at a boiling temperature for 30 minutes to prepare a beard spelea flower and an extract of beetroot.

Example 1: Prevention of hair loss and preparation of hair growth promoting composition

40% by weight of SML0128 manufactured by Sigma, 30% by weight of L-arginine and 30% by weight of copper tripeptide-1 (GHK-Cu) as a pharmaceutically acceptable salt of the compound of the formula (1) A composition was prepared.

Example 2: Preparation of hair loss prevention and hair growth promoting composition

40% by weight of SML0128 manufactured by Sigma, 15% by weight of L-arginine, 20% by weight of copper tripeptide-1 (GHK-Cu), 5% by weight of pullulan, 5% by weight of albumin, 10% by weight of boswellylic acid, and 5% by weight of the extract of the whiskers and balsam mixture prepared in Preparation Example 1 were mixed to prepare a composition for promoting hair loss prevention and hair growth.

Comparative Example 1: Preparation of Hair Loss Prevention and Hair Growth Promoter Composition

As a pharmaceutically acceptable salt of the compound of the formula (1), hair loss preventing and hair growth promoting agent was prepared by 100% of SML0128 manufactured by Sigma.

≪ SML0128 manufactured by Sigma &

Examples 3 to 4 and Comparative Example 2: Hairtonic production comprising hair loss prevention and hair growth promoting composition

A hair tonic composition was prepared according to the composition of Table 1 below.

ingredient Example 3 Hair tonic Example 4 Hair tonic Comparative Example 2 Hair tonic Hair loss prevention and hair growth promoting composition 30
(Preparation of Example 1) 30
(Preparation of Example 2) 30
(Preparation of Comparative Example 1) Resorcinol 0.1 0.1 0.1 menthol 0.05 0.05 0.05 Panthenol 0.2 0.2 0.2 Salicylic acid 0.1 0.1 0.1 Tocopheryl acetate 0.1 0.1 0.1 Pyridoxine hydrochloride 0.1 0.1 0.1 Castor oil 5.0 5.0 5.0 Pigment Suitable amount Suitable amount Suitable amount Spices Suitable amount Suitable amount Suitable amount ethanol Suitable amount Suitable amount Suitable amount Purified water Balance Balance Balance Sum 100 100 100

Test Example: Effect of stimulation of hair growth or hair loss inhibition

Test Example 1: Evaluation of proliferation of dermal papilla cells

The effects of the compositions of Examples 1 and 2 and the sample of Comparative Example 1 on the cell proliferation of human hair dermal papilla cells were examined by using human hair dermal papilla cells (HHDPC) Sciencell, cat. No. 2400).

The cells were plated on a 96-well plate so that human dermal papilla cells (Sciencell, cat. No. 2400) were cultured at 0.5 × 10 ⁴ cells in a MSC (Mesenchymal Stem Cell) medium, a culture medium containing 10% fetal bovine serum inoculation and for 24 hours and then cultured under 37 ℃, 5% CO ₂ wet condition. The culture was treated with the above samples at a concentration of 10 μg / ml and cultured for 72 hours. 5 mg of MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide) Insert the 20㎕ the culture was incubated for 4 hours in a 37 ℃, 5% CO ₂ wet condition. In culture, purple crystals form in living cells. After 4 hours of incubation, the medium was removed, DMSO 100 was added, the crystal was dissolved in a shaking incubator for 10 minutes, and the absorbance was measured at 570 nm to measure the degree of cell growth. The test results are shown in Table 2 below as a percentage of the control group as the non-treatment group.

division Growth rate (%) Control group (untreated group) 100 The composition of Comparative Example 1 (the compound of Formula 1) 132 (1) + L-arginine + copper tripeptide-1 (GHK-Cu)) of the composition of Example 1 139 The composition of Example 2 (additional compound such as compound of formula 1 + L-arginine + copper tripeptide-1 (GHK-Cu) + pullulan) 149

The results of Table 2 above confirm that the samples of the examples of the present invention promote remarkable proliferation of dermal papilla cells compared with the control and the composition of Comparative Example 1. [ In particular, the composition of Example 2 was found to better promote the proliferation of dermal papilla cells.

Test Example 2: Evaluation of proliferation effect of human keratinocyte (HaCaT cell)

The effect of the compositions of Examples 1 and 2 and the sample of Comparative Example 1 on the cell growth of human keratinocytes was examined using keratinocytes (HaCaT cell) (Dr. NE Fusenig (Heidelberg, Germany) , And evaluated in the same manner as in Test Example 1. The RPMI medium containing 10% FBS (fetal bovine serum, Cambrex) was used as the medium, and the results are shown in Table 3 below as a percentage of the control group .

Test group Growth rate (%) Control group (untreated group) 100 The composition treated group of Comparative Example 1 (salt of the compound of Chemical Formula 1) 127 (Composition salt of compound 1 + L-arginine + copper tripeptide-1 (GHK-Cu)) in the composition of Example 1 136 The composition of Example 2 (additional components such as salts of compounds of Formula 1 + L-arginine + copper tripeptide-1 (GHK-Cu) + pullulan) 147

According to the results shown in Table 3, the samples of the examples of the present invention were found to promote proliferation of keratinocytes remarkably as compared with the control and the composition of Comparative Example 1. In particular, the composition of Example 2 was found to promote the proliferation of keratinocytes to be superior.

Test Example 3: Animal experiment for hair growth effect

6-week-old female C57BL / 6 mice with the genetic characteristic of spontaneous hair loss, which is frequently used as an animal model, was used to examine the effect of the compositions of Examples 1 and 2 and the sample of Comparative Example 1 on improving hair loss symptoms Respectively. Female C57BL / 6 mice were subjected to primary shaving using an electric clipper cut, followed by shaving with a shaving razor. The shaving razor was applied to the cervical vertebra The length and length of the midline of the dorsum were compared with the width of 1cm or more on each side of the median line, and only the individuals showing a homogeneous pink color of the dorsal skin were selected for the experiment. After applying a brush to the hair removal part, 200 쨉 L of the test material was dispensed on the end of the brush using a micropipette, and then uniformly applied to the entire hair removal part once a day for 21 days in the vertical direction. All test results were expressed as mean ± standard deviation. For all data, homogeneity analysis of variance was performed with Turkey test and ANOVA (one way analysis of variance) (Dunnett's t-test).

Test Example 3-1: Analysis of wool area

The compositions of Example 1 and Example 2 and the sample of Comparative Example 1 were transdermally administered to female C57BL / 6 mice, and then subjected to a hair growth cycle over a total of 4 times on days 0, 7, 14 and 21, Were visually confirmed. As a result, as shown in Table 4 and Fig. 1, hair growth was observed from the beginning 7 days to hairy tail side back part and neck side back part. Treatment of the salt of the compound of formula 1 (SML0128 produced by Sigma), the composition of Example 1 and the composition of Example 2 in comparison to the control group that did not undergo anything from Day 14 resulted in better hair regrowth Effect.

Furthermore, the composition of Example 1 and the composition of Example 2 exhibited a more remarkable hair regrowth effect, as compared to the salt of the compound of Formula 1 (SML0128 produced by Sigma). Specifically, the composition of Example 2 exhibited a hair regrowth effect more prominent than that of Example 1.

Control group Comparative Example 1 Example 1 Example 2 0 days 0 0 0 0 7 days 8.7 ± 21.2 10.9 ± 42.3 12.9 ± 11.3 15.9 ± 22.5 14 days 58 ± 72 89.3 ± 65.9 97.3 ± 06.5 105.3 ± 15.5 21st 86 ± 46 94.5 ± 21.6 102.2 + - 21.6 111.0 ± 36.7

** Promotes hair re-growth by sample treatment of alopecia induced C57BL / 6 mice

Test Example 3-2: Histopathological Analysis

In order to confirm the morphological changes of female C57BL / 6 mouse hair follicles, the skin tissue collected on the 21st day after transdermal administration was stained with hematoxylin-eosin and observed with an optical microscope to confirm the number of hair follicles, The results are shown in Table 5 below.

Test group Number of dormant hair follicles (Telogen number) Control group (untreated group) 6.2 ± 13 The composition treated group of Comparative Example 1 (salt of the compound of Chemical Formula 1) 8.5 ± 0.7 (Composition salt of compound 1 + L-arginine + copper tripeptide-1 (GHK-Cu)) in the composition of Example 1 10 ± 0.9 The composition of Example 2 (additional components such as salts of compounds of Formula 1 + L-arginine + copper tripeptide-1 (GHK-Cu) + pullulan) 12 ± 1.1

** Results of measurement of number of resting hair follicles following sample treatment in alopecia induced C57BL / 6 mice As shown in Table 5, when treated with the salt of the compound of Chemical Formula 1 (SML0128 produced by Sigma), the control group The number of hair follicles in the resting period was increased.

However, when treated with the composition of Example 1 of the present invention, it was confirmed that the number of hair follicles at rest was significantly increased as compared with the control group and Comparative Example 1. [

In particular, when treated with the composition of Example 2 of the present invention, the number of hair follicles in the resting period was significantly increased as compared with Example 1.

Test Example 4: Clinical trial for prevention of hair loss and promotion of hair growth

100 ml of the hair tonic composition of Example 4, Example 5 and Comparative Example 2 were put into a spray container and the patients were alopeccated twice a day (morning and evening) (8 male and 2 female ), And the effect was confirmed. The test was conducted for 15 weeks.

When the patient visited the hospital for the first time, the hair loss was diagnosed, the hair loss area was recorded and the black spot was tattooed on the most severe area so that the same area could be measured every time the hair loss was measured. The number of hairs per unit area (number of hairs / ㎠) of hair loss area was measured using a simple hand-held phototricho gram (Folliscope, Lead M Co., Seoul, Korea). The number of hairs per unit area was measured by using a 30x lens and the number of terminal hair in a unit area was calculated after the hair loss area around the display area was photographed.

Table 6 shows changes in the number of hairs (number of hairs / cm2) measured at a certain point in time before and after drug administration in the alopecia patients. 2 and 3 are photographs taken at the starting point and the 15th point of time of the subjects 1 and 7 using the hair tonic of Example 4, respectively.

As shown in Table 6, in comparison with the case where the hair tonic of Comparative Example 2 (including SML0128 manufactured by Sigma) was applied, Example 3 of the present invention (including the composition of Example 1) and Example 4 In the case of the experimental groups to which the hair tonic of the Example 2 was applied, the number of the increased hair was remarkably increased.

In particular, it can be seen that the number of hair increased was significantly increased when the hair tonic of Example 4 was compared with the hair tonic of Example 3 of the present invention.

Test Example 5: Evaluation of side effects

The side effects of the hair tonics of Example 3, Example 4 and Comparative Example 2 used in the process of Test Example 4 were confirmed through questionnaires, and the results are shown in Table 7 below.

Example 3 Hair tonic Example 3 Hair tonic Comparative Example 2 Hair tonic Number of subjects 30 people 30 people 30 people Disclaimer (for 15 weeks) 0 people 0 people 0 people Number of side effects 0 people 0 people 0 people

As shown in Table 7, it was confirmed that the hair loss prevention and hair growth promoting composition of the present invention was completely safe because no side effects were exhibited at all and no treatment abandoner occurred at all.

Claims (4)

Wherein the composition comprises 20 to 50% by weight of a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, 10 to 40% by weight of L-arginine, 10 to 40% by weight of copper tripeptide-1 (GHK- An extract of a mixture obtained by mixing 5 to 20% by weight of pullulan, 5 to 20% by weight of corn albumin, 5 to 20% by weight of boswellinic acid, and 0.5 to 1: 10 to 20% by weight,
The cosmetic composition for preventing hair loss and promoting hair growth according to claim 1, wherein the extract of the whitish phalaenopsis flower and the mixture of persimmon extract is an extract which is extracted from ethanol at boiling temperature for 0.3 to 1.5 hours using ethanol as an extraction solvent.
[Chemical Formula 1]

In Formula 1, R 1 and R 2 may be the same or different and may be selected from the group consisting of hydrogen, (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy and halogen. delete delete The method according to claim 1,
The cosmetic composition for preventing hair loss and promoting hair growth, wherein the cosmetic composition is a shampoo or a hair tonic.

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