CN106937957B

CN106937957B - Composition for treating androgenetic alopecia and shampoo thereof

Info

Publication number: CN106937957B
Application number: CN201710263979.5A
Authority: CN
Inventors: 刘佳
Original assignee: Beijing Yuewei Technology Co ltd
Current assignee: Beijing Yuewei Technology Co ltd
Priority date: 2017-04-21
Filing date: 2017-04-21
Publication date: 2021-03-30
Anticipated expiration: 2037-04-21
Also published as: CN106937957A

Abstract

The invention discloses a composition for treating androgenetic alopecia and a shampoo thereof, wherein the composition comprises 41-50% of potassium azeloyl diglycosidate, 6-12% of water-soluble hesperidin, 1.6-9% of vitamin C and 1.2-6.3% of vitamin B by weight percentage. The use method of the composition comprises the following steps of mixing the composition and deionized water according to a mass ratio of 0.8-1.2: 9, mixing, heating to 40 ℃, stirring at constant temperature for 10min, and then naturally cooling to room temperature under stirring. The composition provided by the invention can be used as a 5 a-reductase inhibitor external preparation for reducing dihydrotestosterone in scalp and hair follicle and perfectly enhancing the inhibition effect of 5 a-reductase; the potassium azelate diglycidylate is matched with vitamin B for use, so that the absorption and the effect of the vitamin B are enhanced, and the effect of the potassium azelate diglycidylate on inhibiting 5 a-reductase is improved; the blood flow of scalp capillaries can be improved by matching methyl hesperidin with vitamin C, so that the hair growth is facilitated, and the effect similar to that of minoxidil is achieved.

Description

Composition for treating androgenetic alopecia and shampoo thereof

Technical Field

The invention belongs to the field of medicines, and particularly relates to a composition for treating androgenetic alopecia, shampoo containing the composition and a using method of the composition.

Background

Male Pattern Alopecia (MPA) is also known as androgenetic alopecia, hereditary alopecia, seborrheic alopecia, and alopecia prematura. Statistically, about 95% of patients with alopecia belong to male pattern alopecia. The disease is mostly developed in men of 20-30 years old, and the incidence rate of the disease is increased with the increase of the age. Although the disease name includes the word "male", it is not a patent for men and women will also be affected. Male pattern alopecia is a multifactorial disease that has been found in recent years in medicine to be associated primarily with 5 a-reductase and DHT (dihydrotestosterone) levels.

Hair grows from the root (hair follicle), and the hair matrix cells and melanocytes in the hair follicle multiply, combine with keratin, harden to lose biochemical activity, and then drill out of the hair follicle, i.e., grow hair. The growth cycle of hair can be divided into three stages of growth period, catagen period and resting period. The growth period of one hair is 5-7 years, the catagen period is 2-3 weeks, and the resting period is about 3 months. Humans have approximately 10 million hairs, and the growing period of hair is about 95%. The catagen and telogen phases were 5%. After the hair in the rest period falls off, new hair in the 'growing period' grows out, and people can always show one hair. However, if there is a relatively large amount of sensitive 5 a-reductase in the cytoplasm of human hair matrix cells, testosterone produced in vivo is converted into dihydrotestosterone (5 times stronger in androgen than before) by the catalytic action of 5 a-reductase as blood circulates to the hair follicle and enters the hair matrix cells. The dihydrotestosterone enters the nucleus of the hair follicle at the top of the head, so that the production of energy substances is hindered, the synthesis of hair protein is further hindered, and hair matrix cells are apoptotic in advance to become hair in a resting period. That is, the "anagen" phase of hair is shortened and the "telogen" phase is advanced, which is a period of about 3 months in life, and when new hair has not yet grown, old hair begins to fall off, and androgenic alopecia thus occurs. Androgens are also present in women and, therefore, "androgenic alopecia" also occurs.

Male alopecia is manifested by a receding hairline and a loss of hair at the top of the head. Typing according to Hamilton typing method can be classified as type I: normal hairstyle in puberty; type II: slight withdrawal of the hairline on both sides; type III: the frontotemporal part is obviously withdrawn and takes an M shape; type IV: the forehead moves backwards, the vertex hair rotation part is sparse, but the forehead does not fall off completely; and V type: alopecia occurs at the frontotemporal part and the top part, and a broken belt is formed in the middle; type VI: the baldness spots are fused, the forehead basically falls off, the trend of the top of the head is continuously expanded, and only narrow hair bands are separated; type VII: only one circle of hair in the edge area is stored. Male baldness in women generally occurs later, progresses more slowly, and is less symptomatic than men. The main female is characterized by progressive and sparse hair, and diffuse distribution, and is a slowly-developing diffuse alopecia with few high-volume anaphora. It is caused by androgen increase due to life habit disorder and endocrine disturbance.

The alopecia treatment must be carried out by early discovery and early treatment, the number and the density of hair follicles on the scalp of each person are determined at birth, each hair follicle can only grow 20-25 hairs for a lifetime, and then the hairs are not grown. If the treatment is not carried out in time, the concentration of the scalp dioxygen testis is reduced by inhibiting the activity of 5 a-reductase after the hair growth potential of the hair follicle is exhausted, and new hair can not be produced.

Dihydrotestosterone is the product of testosterone catalyzed by 5 a-reductase in the target tissue and is widely distributed in the systemic blood. Dihydrotestosterone can be combined with a special receptor to form a compound, enters cells, is connected with a nuclear receptor and is combined with chromatin, and further synthesis of RNA and DNA is influenced to play a series of physiological functions. After male adults, excessive dihydrotestosterone can cause pathological phenomena such as acne and alopecia. Recent studies have demonstrated that type II 5 a-reductase is abundantly present in fibroblasts of the follicular root sheath, prostate, terminal blood vessels, epididymis, fetal genital skin and adult genital skin. Dihydrotestosterone (DHT), which is formed by the conversion of testosterone by 5 a-reductase, atrophies the hair follicle, leading to hair loss, and the reduction of this sex hormone is irreversible. The sex hormone reduction process only occurs in the forehead and the hair follicle at the top of the head, and the hair at the lateral part and the back part of the head is protected by the longevity gene, so that the reaction does not occur, and the hair is not shed. Through detection and comparison of serum DHT levels of people in male pattern alopecia groups and normal control groups, serum DHT levels of people in male pattern alopecia groups are found to be obviously higher than those of the normal control groups, and further testifies that testosterone is combined with 5 a-reductase and converted into dihydrotestosterone, and the dihydrotestosterone causes alopecia.

Androgenetic alopecia progresses if untreated, but if controlled properly at the initial stage, it improves and delays the time to loss. Inhibition of 5 a-reductase, i.e., reduction of the concentration of the dioxygenase in vivo by inhibiting the activity of 5 a-reductase, can help to solve the problem of hair loss. There are two current methods of treating androgenetic alopecia: medicine and hair transplantation. In the aspect of medicine, the medicine is mainly used for treating alopecia in the initial stage of alopecia or the condition that hair follicles are only withered. At present, the most effective combination for treating androgenetic alopecia is finasteride + minoxidil, finasteride (Baofu) and minoxidil are anti-alopecia medicines approved by the FDA in the United states, finasteride (Baofu) is mainly taken orally, and plays a role by reducing the influence of male hormone on hair follicles, finasteride (Baofu) can inhibit 5 a-reductase in vivo, so that the generation of dihydrotestosterone is inhibited, and the invention can be used as a 5 a-reductase inhibitor external preparation for reducing dihydrotestosterone in scalp and hair follicles and perfectly enhancing the 5 a-reductase inhibition effect. Minoxidil is used for external application, has concentration of 2% (for male and female use) and concentration of 5% (for male use), mainly prolongs hair follicle growth cycle, keeps blood supply smooth, promotes hair follicle nutrient absorption to grow hair, and is suitable for various types of alopecia. The externally applied medicine has a narrow selection range, and almost no products which can replace minoxidil and external preparations for inhibiting 5 a-reductase exist in the market, so that the blank of the external preparation for inhibiting the 5 a-reductase is filled.

Disclosure of Invention

The invention aims to provide a composition of an external preparation which is safe, has no side effect, has good effect of treating androgenetic alopecia, can replace minoxidil and inhibit 5 a-reductase simultaneously, a shampoo containing the composition and a using method of the composition.

In order to achieve the technical purpose, the technical scheme adopted by the invention is as follows:

a composition for treating androgenetic alopecia comprises 41-50 wt% of potassium azelate diglycosite, 6-12 wt% of water-soluble hesperidin, 1.6-9 wt% of vitamin C and 1.2-6.3 wt% of vitamin B.

Azelaic acid, the common name azalea acid, has the following characteristics: 1. the antibacterial effect is achieved, the protein synthesis of bacteria is inhibited, the bacteria on the surface of the skin and in hair follicles are directly inhibited and killed, the bacteria have the killing effect on staphylococcus epidermidis, pseudomonas aeruginosa, proteus, candida albicans, propionibacterium acnes and the like at higher concentration (>250mmol/L), the minimum inhibitory concentration is 25mmol/L, the play effect depends on PH, the cells can be quickly entered to play the antibacterial effect when the PH is low, and the dosage of the azelaic acid permeating the abnormal cells is more than that of the normal cells; 2. inhibiting the generation of free radicals, inhibiting the generation of active oxygen free radicals, and having anti-inflammatory effect, wherein azelaic acid can inhibit the hydroxylation of aromatic compounds induced by active oxygen free radicals and the peroxidation of arachidonic acid in vitro; 3. preventing skin keratinization, resisting cutin of normal skin and acne-infected skin, reducing synthesis of filamentous keratin, and preventing hair follicle hyperkeratosis; 4. effects on skin pigment cells: on the one hand, azelaic acid competitively inhibits tyrosinase in hyperactive melanocytes, reduces pigment synthesis, but does not inhibit pigment synthesis in normal pigment cells, and on the other hand, it disrupts melanocyte mitochondrial respiratory chain, inhibits cellular DNA synthesis, and prevents abnormal melanocyte proliferation. Because of the characteristics, the face beautifying and skin caring cream is often used for manufacturing face beautifying and skin caring products and treating facial acne.

Azelaic acid also has the functions of regulating sebaceous gland, competitively inhibiting 5 a-reductase, inhibiting the conversion of excessive androgen into dihydrotestosterone, and reducing skin greasiness induced by dihydrotestosterone factors. Azelaic acid has been variously demonstrated as a potent 5 a-reductase inhibitor in human skin, and 5 a-reductase was almost completely (98%) inhibited at 3mmol/l in a study reported by British Journal of Dermatology (Stamatidis. 1988; 119: 627-. It is used as DHT inhibitor to prevent alopecia. Because of insolubility, high melting point, large dosage, easy color change and poor compatibility, the application of the azelaic acid is greatly limited, the azelaic acid derivative potassium azelate is easy to dissolve in water, and compared with azelaic acid, the azelaic acid derivative potassium azelate has excellent safety and stability, and no side effect is caused after clinical safety in four stages.

In addition, according to clinical findings, the combined use of azelaic acid or derivatives thereof and vitamin B group can play a mutual enhancing and promoting role.

Hesperidin (also called hesperidin or hesperidin) is mainly present in pericarp, fruit juice and seeds of citrus plants of Rutaceae, and is present in the pericarp at a maximum content of about 3%. Hesperidin belongs to dihydroflavonoids, is nontoxic and cannot be synthesized by human bodies. It is often used as an adjuvant and hemostatic for treating hypertension clinically. The hesperidin has the same efficacy as vitamin P, can enhance the effect of vitamin C when being used together with the vitamin C, has stronger antiviral and antibacterial effects, and can inhibit the propagation of influenza viruses in large dose; can inhibit tyrosinase which causes skin blackening, and can be used for treating dermatoses such as black speck and freckle. Has effects in maintaining normal permeability of blood vessel, and preventing and treating capillary hemorrhage, gingival hemorrhage, etc. Can strengthen capillary resistance, enhance elasticity and toughness of capillary, normalize capillary permeability, improve blood flow of scalp capillary by combining with vitamin C, and promote hair growth (Kawaguchi, Goro. Japanese patent application laid-open No. 93, 17, 321). Consistent with the action mechanism of minoxidil. At present, hesperidin has certain application in the pharmaceutical and cosmetic industries, but the effect is not obvious, which is mainly related to the characteristics that hesperidin is difficult to dissolve in water and insoluble in a fat-soluble solvent. Therefore, the modified water-soluble hesperidin should be selected.

The potassium azeloyl diglycoate adopted by the invention has the function of competitively inhibiting 5 a-reductase, inhibits the conversion of excessive androgen into dihydrotestosterone, reduces excessive skin grease induced by dihydrotestosterone factors, can radically solve androgenic alopecia, and can perfectly enhance the inhibition effect of 5 a-reductase as an external preparation of a 5 a-reductase inhibitor; the clinical findings show that the vitamin B can be used together with vitamin B to mutually promote and enhance the effects; the water-soluble hesperidin can enhance the resistance of capillary vessels, enhance the elasticity and toughness of the capillary vessels, ensure normal capillary vessel penetration, improve the blood flow of scalp capillary vessels by matching with vitamin C, is beneficial to the growth of hair, has the same action mechanism as minoxidil, and can achieve the same effect as minoxidil.

Further limited, the extract also comprises 10.5 to 28 percent of arborvitae twig and leaf alcohol extract and 3.4 to 12 percent of propolis.

Cacumen Platycladi (also known as Chamaecyparis obtusa and Thuja Cordata) is evergreen arbor, and its tender branch, leaf and fruit can be used as medicine, and has bitter and astringent taste, slightly cold nature, and has effects of cooling blood, stopping bleeding, blackening beard and hair, and relieving cough and asthma. Is mainly used for treating bleeding caused by recklessly blood flow due to blood heat, and has the effects of relieving cough, eliminating phlegm, lowering blood pressure, preventing alopecia and the like. The cacumen Platycladi extract has strong inhibitory effect on biosynthesis of leukocyte LTB4 and 5-HETE (5-lipoxygenase), and also has strong inhibitory effect on cyclooxygenase, and cacumen Platycladi has anti-inflammatory effect by inhibiting activity of 5-lipoxygenase and cyclooxygenase. Has inhibitory effect on Staphylococcus aureus and Staphylococcus catarrhalis. The extract of cacumen Platycladi contains phenolic substances, and also has anti-candida activity, the pathogenesis of androgenetic alopecia is not completely clear, and the inflammation reaction driven by microorganisms is abutted against hair follicle, which may be related to abnormal hair state. The antibacterial property of the cacumen biotae helps to condition the scalp and improve the scalp environment.

Propolis is an effective substance used by bees for maintaining the health of the whole group, has the effects of resisting bacteria, maintaining beauty and keeping young and promoting cell regeneration, is a rare natural resource and is named as purple gold. Recently, research by scientists of japan provided a new basis for the efficacy of propolis on hair, and in this research, they studied whether propolis can stimulate the growth of hair in mice. The results show that propolis promotes the growth of hair by inducing the proliferation of hair keratinocytes, and thus serves to promote the benign growth of "fine hair" generated after hair growth.

Further limited, the composition also comprises 6 to 12 percent of azone and 0.01 to 0.03 percent of EDTA-2 Na.

Furthermore, AZONE (AZONE) is a high-efficiency skin penetration enhancer, has strong transdermal effect on hydrophilic and lipophilic medicaments, and can increase the absorption of the medicaments, thereby enhancing the curative effect of the medicaments; EDTA-2Na is used to adjust the pH of the composition.

Further limited, the water-soluble hesperidin is methyl hesperidin.

The solubility of methyl hesperidin is 12500 times of that of conventional hesperidin, and the solubility in water exceeds 25%.

Further limited, the vitamin B is 50.7 to 3.5 percent of vitamin B, 60.5 to 2 percent of vitamin B and 80.5 to 2 percent of vitamin B.

The vitamin B5 is a permeable humectant, has good permeability, can easily permeate into hair roots, enables the hair to be soft, elastic and easy to comb, can increase the hyaluronic acid content of the skin after being absorbed by the skin and act together with the B6, and can stimulate cell division and regeneration and repair tissues; vitamin B6 can improve oil secretion and regulate skin oil balance; vitamin B8 (also known as biotin) is a basic substance for promoting keratin growth and is also the basis of human body adhesive substances, hair loss and looseness symptoms can be caused by lack of the vitamin B8, and research reports indicate that the biotin can treat alopecia caused by biotin deficiency and improve the defects of easy breakage and poor hair quality.

The invention also provides a using method of the composition, which comprises the following steps of mixing the composition and deionized water according to a mass ratio of 0.8-1.2: 9, mixing, heating to 40 ℃, stirring at constant temperature for 10min, and then naturally cooling to room temperature under stirring.

The invention also provides a shampoo containing the composition, wherein each 1000ml of the shampoo comprises 95g to 120g of the composition.

Further limited, the pH value of the shampoo is 5.5-6.2 at 30 ℃, and the viscosity is 6000-8000 MPa.s.

The composition provided by the invention utilizes the effect of potassium nonanedioyl diglycoate in inhibiting 5 a-reductase, inhibits excessive androgen from being converted into dihydrotestosterone, reduces excessive skin oil induced by dihydrotestosterone factors, can radically solve androgenic alopecia, and can improve the 5 a-reductase inhibition effect as an external preparation of a 5 a-reductase inhibitor; the potassium nonanedioyl diglycoate is matched with vitamin B for use, so that the effects of the potassium nonanedioyl diglycoate and the vitamin B are enhanced, and the effect of the potassium nonanedioyl diglycoate in inhibiting 5 a-reductase is improved; the methyl hesperidin can enhance the resistance of capillary vessels, enhance the elasticity and toughness of the capillary vessels, ensure that the capillary vessels permeate normally, improve the blood flow of scalp capillary vessels by matching with vitamin C, facilitate the growth of hair and play the same role as minoxidil; meanwhile, the antibacterial property of the cacumen biotae alcohol extract is utilized to help condition the scalp and improve the scalp environment; propolis is used for promoting the benign growth of 'small villi' generated after hair growth.

The composition provided by the invention can be prepared into an external preparation by dissolving in deionized water, is convenient to apply, and does not feel greasy and uncomfortable after being applied.

The composition provided by the invention can also be added into common shampoo base liquid to prepare shampoo.

Detailed Description

In order that those skilled in the art can better understand the present invention, the following embodiments are provided to further illustrate the present invention.

Also comprises 10.5 to 28 percent of arborvitae tops alcohol extract, 3.4 to 12 percent of propolis, 6 to 12 percent of azone and 0.01 to 0.03 percent of EDTA-2 Na.

Wherein the water-soluble hesperidin is methyl hesperidin.

The vitamin B comprises 50.7-3.5% of vitamin B, 60.5-2% of vitamin B and 80.5-2% of vitamin B.

Example one

Preparation of an external coating formulation with the composition:

50.00g of potassium nonanedioyl diglycoate, 20.00g of cacumen biotae extract, 10.00g of azone, 10.00g of methyl hesperidin, 6.00g of vitamin C, 52.00g of vitamin B, 61.00g of vitamin B, 81.00g of vitamin B, 8.00g of propolis, 0.02g of EDTA-2Na and 1000ml of deionized water are respectively taken, heated to 40 ℃, stirred for 10min at constant temperature and then naturally cooled to room temperature under stirring to obtain the external preparation.

Example two

Preparing a shampoo containing the composition:

step one, introducing A1 into a production pot, shearing and homogenizing at a high speed for about 5min while stirring, adding A2 while stirring, heating to about 85 ℃ while stirring, scraping at a constant temperature while stirring for about 30min, adding A3 while stirring, cooling circularly while stirring, cooling to below 40 ℃, transferring to a storage pot, adding a proper amount of waste water, naturally cooling to room temperature while stirring, and using as a storage base material;

step two, introducing B1 into a production pot, shearing and homogenizing at a high speed for about 2min under stirring while scraping, adding B2, shearing and homogenizing at a high speed for about 3min under stirring while scraping, adding B3, heating to about 85 ℃ under stirring while scraping, stirring at a constant temperature for about 30min while scraping, adding B4 under stirring while homogenizing, cooling circularly under stirring while scraping, cooling to about 40 ℃, adding a proper amount of water loss and B5 under stirring while scraping, stirring for about 5min while scraping, adding B6, adding deionized water according to actual conditions to adjust the volume of the shampoo to 1000ml, adding sodium chloride and citric acid to adjust the pH value of the shampoo to 5.5-6.2 and the viscosity to 6000-8000MPa.s, and continuing to scrape and stir for about 5min after shearing at a high speed for about 2min while homogenizing and stirring.

Wherein A1, A2, A3, B1, B2, B3, B4, B5 and B6 comprise the following substances and contents:

800 subjects aged 18 to 41 were selected for a 12 month clinical study with 10% female and 90% male; the male subjects are typed according to a Hamilton typing method, wherein the type II subjects account for 20 percent, the type III subjects account for 25 percent, the type IV subjects account for 25 percent and the type V subjects account for 20 percent. Subjects were equally divided into four groups, each group containing female subjects, type II subjects, type III subjects, type IV subjects, type V subjects. The first group of subjects used the formulation prepared in example one, 2ml each time, 2 times daily, applied to the scalp; the second group of subjects used the shampoo prepared in example two, which was washed once every two days; the third group of subjects used a vitamin B-depleted formulation, the other ingredients being in accordance with example one; the fourth group of subjects used shampoo with potassium azeloyl diglycoate removed and the other ingredients were identical to those in example one.

Four criteria were used in the study to assess hair growth, namely: hair count, grading assessments by a panel of dermatologists from photographs, investigator's assessment, and self-assessment of patients.

Following these 800 subjects, the following data were obtained:

as can be seen from the above table, using the formulation provided in example one, 70% of the subjects stopped hair loss, and nearly 69% of the people developed new hair at the site of hair loss; after using the shampoo provided in example two, nearly 65% of the subjects stopped losing hair, and about 55% of the subjects developed new hair; in contrast, in the third and fourth groups of the control group, the effect was greatly reduced due to the removal of vitamin B in the third group and the absence of potassium azeloyl diglycoate in the fourth group, and it can be seen from one aspect that the effect of treating alopecia was better due to the use of vitamin B in combination with potassium azeloyl diglycoate.

The composition and shampoo for treating androgenetic alopecia and the use method of the composition provided by the invention are described in detail above. The description of the specific embodiments is only intended to facilitate an understanding of the method of the invention and its core ideas. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.

Claims

1. A composition for treating androgenetic alopecia comprising: according to weight percentage, the composition comprises 41 to 50 percent of potassium nonanedioyl diglycoate, 6 to 12 percent of water-soluble hesperidin, 1.6 to 9 percent of vitamin C and 1.2 to 6.3 percent of vitamin B;

2. The composition for treating androgenetic alopecia according to claim 1, wherein: also comprises 10.5 to 28 percent of arborvitae tops alcohol extract and 3.4 to 12 percent of propolis.

3. A composition for use in the treatment of androgenetic alopecia according to claim 1 or 2, wherein: also comprises 6 to 12 percent of azone and 0.01 to 0.03 percent of EDTA-2 Na.

4. A composition for use in the treatment of androgenetic alopecia according to claim 1 or 2, wherein: the water-soluble hesperidin is methyl hesperidin.

5. A shampoo comprising a composition for treating androgenetic alopecia, wherein: a shampoo comprising 95g to 120g of the composition of any of claims 1 to 4 per 1000ml of shampoo.

6. The shampoo according to claim 5 comprising a composition for treating androgenetic alopecia wherein: at 30 ℃, the pH value of the shampoo is 5.5-6.2, and the viscosity is 6000-.