KR20100060754A - External composition for enhancing hair growth through transdermal absorption - Google Patents

Abstract

PURPOSE: An external use composition for promoting hair growth through percutaneous absorption is provided to transfer hair growth promotion ingredient to hair follicle and to supply nutrition. CONSTITUTION: An external use composition for promoting hair growth contains an ethosome carrier in which a hair growth promotion ingredient is intensive. The hair growth promotion ingredient is 4-pyrrolidine 2,6-diaminopyrimidine-1-oxide, vitamin B5 derivative, Swertiall, glycyrrhizin and glycyrrhetic acid, nicotinamide, adenosine, glyceryl pentadecanoate, 6-benzyl aminopurine, eugenol, or dialkylmonoamine derivative. The ethosome carrier has a particle diameter of 10-800nm and comprises ethanol and lecithin.

Description

External composition for enhancing hair growth through transdermal absorption}

The present invention relates to an external composition for promoting hair growth through percutaneous absorption, and more particularly, by effectively delivering a hair growth promoting component to the hair follicle through a special type of liposome skin delivery system called etosome, thereby expanding blood vessels around the hair follicle. The present invention relates to a composition for promoting external growth of hair, which promotes induction from the resting phase to the growth phase of the hair cycle and induces hair growth and prevents hair loss.

In the modern society that emphasizes beauty, various studies are being actively conducted around the world to treat hair loss and promote hair loss of men or women who suffer severe mental pain from genetic or environmental hair loss.

Human hair is about 100,000 to 150,000, each hair will grow and degenerate through different cycles. Hair is a growing period (Anagen), a degenerative period (Catagen) where metabolic processes slow down while maintaining the shape of the hair, and hair papilla atrophy, hair follicles atrophy gradually, hair roots are pushed upwards, and the hair follicles become smaller (Telogen) The cycle and lifespan of the hair can be changed according to various conditions such as nutrition status, medical history, heredity, constitution, hormone secretion or aging.

Among the existing anti-hair loss treatments, external minoxidil approved by the US FDA, in addition to its vasodilating function as its unique potassium channel opener, induces the growth phase in the resting hair cycle and maintains the induced growth hair cycle. Activity was reported (British Journal of Dermatology. 2004; 150: 186-194).

In addition, an oral administration drug, Finasteride (Propecia; MSD), which inhibits the action of 5 alpha-reductase and inhibits the production of the active male hormone dihydrotestosterone, is marketed as a hair regrowth with the approval of the US FDA. However, there is a limit to use as the occurrence of expensive and side effects are reported. Thus, there has been a continuing need for drugs that are free of hair growth and side effects compared to the two major drugs previously developed.

The mechanism of the hair growth effect of minoxidil, a pyrimidine derivative having the formula 2,4-diamino-6piperidino-pyrimidine-3-oxide, is still not well understood, except that the potassium channel opening effect at the time the drug was first developed It is widely recognized as an effect of vasodilation. Since then, there have been reports on the general potassium channel opening effect and hair growth effect on various pyrimidine derivatives and novel compounds (J Invest Dermatol 2005 124 (4): 686-94), and 4-pyrrolidine is also in the company. A patent has been filed for hair growth using 2,6-diaminopyrimidine-1-oxide (Domestic Patent 2007-0041890).

In addition, various ingredients such as herbal extracts are used as an external preparation composition for promoting hair growth. However, these preparations are limited in their absorption path through the skin when used as external preparations. This can cause problems such as hair clumping due to skin irritation or crystallization.

The absorption path through the skin is known to be the most important absorption path through the stratum corneum, and the passage of the nonpolar lipid layer between keratinocytes is considered to be the most important factor. For this reason, the liposome preparation, which has started to emerge as a means of drug permeation in the skin, has been applied for a liposome base for promoting hair growth (Korea Patent Publication 2004-0040100).

Recently, however, the limits of the efficacy of conventional liposome preparations as drug carriers have been continuously pointed out in the academic community, and a special type of liposome carrier which has greatly improved this is actively studied under the name of ethosome. (J Control Release 2000; 65: 403-418). In this regard, U. S. Patent No. 5,540, 934 refers to the application of the etosome preparation as a transdermal absorption carrier for pharmaceuticals or cosmetics, but it does not specifically disclose the delivery of hair growth promoting components or the improvement of hair growth through it. not.

Therefore, the present inventors have studied to find a formulation having a high hair growth promoting effect and no side effects, and by using a special type of liposome skin delivery system called etosome, it effectively delivers hair growth promoting ingredients to hair follicles and exhibits excellent hair growth and hair growth promoting effects. It has been found that the present invention has been completed.

Accordingly, it is an object of the present invention to provide a topical composition for nourishing hair follicles by transdermal absorption of hair growth promoting ingredients and inducing hair growth from the resting phase to the growing hair cycle to promote hair growth.

In order to achieve the above object, the present invention provides a topical composition for promoting hair growth, comprising an ethosome carrier in which the hair growth promoting component is collected.

The external preparation composition for promoting hair growth according to the present invention effectively delivers hair growth promoting components to hair follicles by using a special type of liposome skin delivery system called etosome to supply nutrients to hair follicles and induces hair growth periods during the growth phase. It can promote hair growth and prevent hair loss, and exhibits excellent hair growth and hair growth promoting effect compared to conventional hair regrowth agents.

The present invention provides a topical composition for promoting hair growth, comprising an ethosome carrier in which hair growth promoting components are collected.

Hereinafter, the present invention will be described more specifically.

The hair growth promoting component of the present invention is delivered to hair follicles through transdermal absorption to prevent hair loss and induce hair growth, and specific examples are minoxidil, 4-pyrrolidine 2,6-diaminopyrimidine 1-oxide (4 -pyrrolidine 2,6-diaminopyrimidine-1-oxide, white porcelain, vitamin B5 derivative (panthenol derivative), sugar extract (Swertiall), uiyiin, glycyrrhizin and glycyrrhetic acid, nicotinamide (niacinamide), vitamin E Derivatives (such as tocopherol acetate), adenosine, pentyldecaneglyceride (PDG), benzyl aminopurine, eugenol, saw palmetto, dialkylmonoamine (dialkylmonoamine) derivatives, isoflavones, hinokitiol, benzylnicotinate and the like.

The minoxidil is an external ingredient approved by the US FDA among existing anti-hair loss treatments, and in addition to the vasodilatation function as its own potassium channel opener, it induces the growth phase in the resting hair cycle and induces the growth phase hair cycle. Continued activity has been reported (British Journal of Dermatology. 2004; 150: 186-194).

The pyrrolidinyldiaminopyrimidine oxide represented by the formula of 4-pyrrolidine 2,6-diaminopyrimidine 1-oxide (4-pyrrolidine 2,6-diaminopyrimidine-1-oxide) is a pyrimidine oxide derivative. It has been found to promote the opening of potassium channels and proliferation of hair follicle papilla cells at the cellular level when used as a component of the external preparation, and to promote hair growth by increasing blood flow around the hair follicles (Korean Patent Publication 2007-0041890).

The vitamin B5 derivative (panthenol derivative) is usually a derivative of pantothenic acid, and pantothenic acid has been found to be an essential growth factor of yeast, and is stable in a neutral solution but destroyed in an acidic or alkaline state, and is particularly weak in heat. Therefore, D-panthenol, D-ethylpanthenol or D-pantothenate calcium or salts have been used as provitamins that are converted to vitamin B5 in a more stable structure. The effects of vitamin B5 are usually summarized on D-panthenol, where the multiple effects on skin and hair are usually reported to be due to three things: 1) the ability to penetrate the skin and hair relatively deeply, 2) the ability to bind water, 3) the conversion of pantothenic acid from skin and hair to produce the effects of vitamin B5. When D-panthenol is added in the cosmetic field, it is deeply delivered to the dermis due to its high permeability, and its hygroscopic capacity affects the state and distribution of moisture in the dermis layer to moisturize. In 1943, H. Pfaltz indirectly confirmed that panthenol was absorbed and converted to pantothenic acid. After treating D-panthenol with ointment for 6 weeks in rats and mice, hypopigmentation and alopecia were higher than oral administration. Reported higher treatment (Pfaltz H., Vitaminforschung, 1943, 13, 236-249). There have also been reports of panthenol external effects on skin epithelial cells in wound and burn healing (Gartner F., Dtsch. Zahnarztl. Z, 1955, 10, 813-5, Cortesse J., GM de France, 1968, 75, 4171-4). When panthenol is applied to the hair, it penetrates to the hair shaft and the hair root and exists as an elastic film on the inner wall, and is surrounded by a thin layer on the outer wall to retain the natural moisture of the hair and to protect it from external drying. Done.

The Thujae semen is a seed of Thuja orientalis (Occidentalis), which is long oval or long cylindrical in shape, long, 3-5 mm long and 2-3 mm in diameter. Baekjain has the efficacy of conscience and concubine (conscience of conscience) and yunjangtongpyeon (Yangjangtongpyeon). It is known to contain many fat oils. Samseonggo's hair piece of Dongbobogam consists of rich, full-form and white porcelain, and its effect is known to bring back the missing mustache or hair, and the prescription is rich and pure berry. Hwangja (자 子) and baekbaek seeds (Baekjain; 柏子仁) 20g each, powdered in bone oil of chicken oil (烏鷄 脂) tossed and dried, put it in a porcelain bowl, put it well for 100 days, take it out and put it out If you apply it for 3-5 days, a new hair comes out (Samsunggo, Namsan-dang). In addition, Baekjain showed 5α-reductase inhibitory activity and its hair growth activity was high in two animal models, and it can be used as a useful material for alopecia by regulating androgen conversion (Journal of Dermatological Science (2003) 31, 91-98).

In addition, the medicinal extract is dissolved in the whole extract of Swertia japonica Makino herb, is called as senburi extract in Japan, medicinal name in Korea, and is called bitter grass of gentian. This extract is a native drug widely used in Japan for abdominal pain, skin infection, hookworm and cold. Common medicinal extracts include 2-4% of swetitiamarin, sertianolin, erythrocentaurin, swetitianol, oleanolic acid and genitianine. It consists of. Glycosides, including swetitiamarin, are known as glycosides and are commonly derived from plants and animals. These can be used to increase skin temperature and promote hair growth, such as cantharide and pepper tincture. Is reported. It is caused by the physical effects of skin temperature rise or by vascular expansion of cholinergic drugs, and this trigger may promote blood flow for the function of the skin. In a paper by Shuji Iwao of the Fragrance Journal of Japan (1996), "About Prospects for Hair Growth Agents," sugar extracts are considered to be a major component of commercial hair growth agents.

Other components that may be included in the present composition include lysine, licorice extract (glycyrrhizin and glycyrrhetic acid), nicotinamide (niacinamide), vitamin E derivatives (tocopherol acetate, etc.), adenosine, pentadecane glyceride (glyceryl pentadecanoate) PDG), benzyl aminopurine, 6-benzyl aminopurine, eugenol, saw palmetto, dialkylmonoamine derivatives, isoflavones, hinokitiol and benzyl As long as nicotinic acid (benzylnicotinate) as a blending component is not a problem in terms of safety, it is not particularly limited and its mechanism of action is not a problem.

The hair growth promoting components are formulated with functions of vasodilating function and hair follicle cell activation of commercial hair restorers, and can be prepared by a known method as a commercially available raw material.

The hair growth promoting component of the present invention is preferably 0.001 to 5% by weight based on the total weight of the composition. This is because when the content is less than 0.001% by weight, the effect is insignificant, and when it exceeds 5% by weight, problems may occur in skin irritation or formulation stabilization.

In the case of conventional liposome preparations, since rigid membranes do not easily pass through the lipid layer between keratinocytes, drug delivery only occurs to the uppermost layer of the skin, thereby reducing its effectiveness. The etosome carrier for improving transdermal absorption of the present invention is composed of ethanol and lecithin to improve the limitation as a drug carrier of a conventional liposome preparation. Etosome is a formulation containing a large amount of ethanol, and ethanol itself weakens the intercellular lipid membrane of the stratum corneum, thereby increasing the skin absorption rate of the active ingredient. Also, the structural membrane of the vesicle composed of lecithin is softened by ethanol, resulting in flexible structural modification. This makes it possible to pass drugs between fine keratinocytes more easily and to deliver drugs deep into the skin.

Ethanol constituting the etosome transporter serves to help the skin absorption of the active ingredient by dissolving the lipid component of the stratum corneum and softening the membrane of the vesicle consisting of lecithin.

The content of the ethanol is preferably 20 to 60% by weight based on the total weight of the composition. When the content is less than 20% by weight, the effect of promoting skin absorption is weak, and when the content exceeds 60% by weight, there is a problem in stabilizing the formulation. Because it can occur.

The lecithin constituting the etosome transporter forms a vesicle structure called liposome due to its structural characteristics, and serves to help the lipid layer pass between keratinocytes of skin through the capture of an active ingredient therein. Lecithin that can be used in the present invention is prepared by extracting from soybean or egg yolk (egg), purified, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidyl glycol, phosphatidylglycol, Phospholipids such as phosphatidic acid and hydrogenated phosphatidylcholine.

The lecithin content of the present invention is preferably 0.1 to 20% by weight based on the total weight of the composition. If the content is less than 0.1% by weight it will not form a vesicle enough to collect the active ingredient sufficiently, if it exceeds 20% by weight because the problem in the formulation stabilization occurs.

Etosome carrier of the present invention has a particle size of 10 ~ 800nm for effective transdermal absorption. If the particle size is less than 10 nm, the effective component is not sufficiently collected and the structure is easily destroyed by external tension, and thus its effectiveness as a carrier decreases. If the particle size exceeds 800 nm, the particle size is large, making it difficult to pass through the stratum corneum. Because it is not done.

The preparation of the etosome carrier that collects the hair growth promoting component may be made through various methods known in the art, but most preferably, a mixture including the above components is applied to the homogenizer. Ethosome preparation by homogenizers can be carried out under various conditions (eg RPM, time, etc.) depending on the desired particle size.

The external preparation composition for promoting hair growth of the present invention includes antioxidants, surfactants, vegetable oils, ester oils, cholesterol, anhydrous or hydrous lower alcohols having 1 to 4 carbon atoms, propylene glycol, butylene, in addition to the active ingredients. Depending on the purpose of use, such as polyols, such as glycol and glycerin, those skilled in the art can appropriately select and blend the components without difficulty.

The external preparation composition for promoting hair growth of the present invention can effectively promote hair growth and prevent hair loss.

Hereinafter, although an Example and a test example are given and this invention is demonstrated in detail, this invention is not limited only to these examples.

Example 1 and Comparative Examples 1 and 2

The external preparation composition for skin of Example 1 and Comparative Examples 1-2 which has the composition of following Table 1 was prepared. 4-pyrrolidine 2,6-diaminopyrimidine 1-oxide was used as a hair growth promoting component. Example 1 was prepared by capturing the hair growth promoting component in an etosome consisting of ethanol and lecithin, and Comparative Example 2 was prepared to include a hair growth promoting component but not to be transdermal absorption through the etosome.

First, pyrrolidinyldiaminopyrimidine oxide, lecithin or Fiji 60 cured castor oil was dissolved in ethanol, and then purified water was added thereto to uniformly prepare the mixture.

ingredient Example 1
(weight %) Comparative Example 1
(weight %) Comparative Example 2
(weight %) ethanol 40.0 50.0 50.0 4-pyrrolidine 2,6-diaminopyrimidine 1-oxide 1.0 - 1.0 lecithin 3.0 - - Sebum 60 Cured Castor Oil - 3.0 3.0 Purified water To 100 to 100 to 100

Test Example 1 Hair Growth Promoting Effect

In order to confirm the hair growth promoting effect of the external preparation composition prepared according to the present invention, the hair of the back of the mouse 7 weeks old (C57BL / 6) was removed, and the back skin was clean and selected seven by each material group. The compositions of Example 1 and Comparative Examples 1 and 2 were applied for 21 days at 150 μl per individual. After 21 days, the photograph was taken, and the weight of the newly grown hair was measured, and the results are shown in FIGS. 1 and 2, respectively.

As can be seen in Figures 1 and 2, Example 1 in which the hair growth promoting component is collected in the etosome transporter according to the present invention, Comparative Example 1 and the hair growth promoting component is not included in the etosome transporter Compared with Comparative Example 2, which did not, hair growth was promoted, and the weight of newly grown hair was also significantly increased. Therefore, it was confirmed that the composition of the present invention acts on the mouse of the resting hair cycle to induce the growing hair cycle and has an excellent hair growth promoting effect.

Test Example 2 Hair Loss Prevention Effect

Thirty subjects with initial hair loss were tested for anti-hair loss for 12 weeks. After the compositions of Example 1 and Comparative Examples 1 and 2 were applied once a day for 12 weeks, after 12 weeks, the hair loss was collected again when the hair was washed and the average number was counted. Table 2 shows.

Example 1 Comparative Example 1 Comparative Example 2 Number of Fallout Hats 48.7 ± 6 76.3 ± 7 60.5 ± 9

As can be seen in Table 2, when treated with the composition of Example 1 according to the present invention it was confirmed that the number of falling off hair significantly reduced than when treated with Comparative Examples 1-2. Therefore, it was found that the composition of the present invention can effectively prevent hair loss.

1 is a photograph of visual observation of the hair growth promoting effect in the mouse of the hair growth promoting external composition of the present invention.

Figure 2 is a graph showing the hair growth promoting effect in the mouse weight of the hair growth promoting external composition of the present invention.

Claims (9)

An external preparation composition for promoting hair growth, comprising an ethosome carrier in which hair growth promoting components are collected. The vitamin B5 derivative according to claim 1, wherein the hair growth promoting component is minoxidil, 4-pyrrolidine 2,6-diaminopyrimidine-1-oxide, white porcelain. (Panthenol derivatives), sugar extract (Swertiall), lysine, licorice extract (glycyrrhizin and glycyrrhetic acid), nicotinamide, vitamin E derivatives, adenosine, pentadecane glyceride (glyceryl pentadecanoate), benzylaminopurine (6) benzyl aminopurine, eugenol, saw palmetto, dialkylmonoamine derivatives, isoflavones, hinokitiol and benzylnicotinate External preparation composition for promoting hair growth, characterized in that at least one. The composition for promoting external growth of hair according to claim 1, wherein the hair growth promoting component is delivered to the hair follicle through transdermal absorption. The composition for promoting external growth of hair according to claim 1, wherein the hair growth promoting component is contained in an amount of 0.001 to 5% by weight based on the total weight of the composition. The external preparation composition for promoting hair growth according to claim 1, wherein the particle diameter of the etosome transporter is 10 to 800 nm. The external preparation composition for promoting hair growth according to claim 1, wherein the etosome transporter is composed of ethanol and lecithin. 7. The external preparation composition for promoting hair growth according to claim 6, wherein the ethanol is contained in an amount of 20 to 60 wt% based on the total weight of the composition. The external composition for promoting hair growth according to claim 6, wherein the lecithin is contained in an amount of 0.1 to 20% by weight based on the total weight of the composition. The external preparation composition for promoting hair growth according to claim 1, wherein the composition prevents hair loss.

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