CN116251086A

CN116251086A - Application of lactic acid and derivatives thereof in promoting hair growth and relieving alopecia

Info

Publication number: CN116251086A
Application number: CN202310114701.7A
Authority: CN
Inventors: 熊耀坤; 洪石希; 刘志勇; 杨思
Original assignee: Jiangxi University of Traditional Chinese Medicine
Current assignee: Jiangxi University of Traditional Chinese Medicine
Priority date: 2023-02-15
Filing date: 2023-02-15
Publication date: 2023-06-13

Abstract

The invention discloses application of lactic acid and a derivative thereof in preparing a composition for promoting hair growth and relieving androgenetic alopecia, wherein the composition takes the lactic acid and the derivative thereof as the only active ingredients. The experiment result shows that the lactic acid and the derivatives thereof can effectively inhibit symptoms of androgen alopecia mice, promote hair growth, and prove the medication safety, and the lactic acid has the advantages of easily available raw materials, natural green, no stimulation, safety, effectiveness and the like, and can be used as a substitute of hair-growing drugs and hair-growing products with high price or side effects. The medicine of the invention has reasonable proportion and simple preparation method, can treat androgen alopecia diseases, and solves the problem of androgen alopecia.

Description

Application of lactic acid and derivatives thereof in promoting hair growth and relieving alopecia

Technical Field

The invention belongs to the technical field of daily chemical industry, and particularly relates to application of lactic acid and derivatives thereof in promoting hair growth and relieving alopecia.

Background

Hair is an important component of the appearance of people, and it is desirable for everyone to have a healthy, organic hair-blacking. However, in recent years, the number of people suffering from alopecia, white hair and alopecia areata is increased year by year, the number of people suffering from alopecia is increased, and the symptoms such as dandruff, scalp inflammation and acne, scalp itching and hair oil are also common, and the problems seriously afflict the normal life of people.

The growth of hair is divided into a growth period, a resting period and a retrograde period, the activation of hair follicle stem cells is a main reason for promoting the increase of hair, keratinocyte Growth Factor (KGF) is a factor secreted by keratinocytes, the expression of epithelial cells and the proliferation and differentiation of keratinocytes can be promoted, a preceding environment is provided for the activation and growth of hair follicle stem cells, vascular endothelial cell growth factor (VEGF) can act on vascular endothelial cells in dermis layers through paracrine, the micro vascular synthesis of local areas of skin is induced to be increased, nutrition ingredients are provided for hair follicle cells, and the hair follicle growth is promoted.

Androgenic alopecia accounts for 80% of all alopecia, is the most prominent alopecia disease, and the prevalence of androgenic alopecia in China is 21.3% in men and 6.0% in women. Modern medicine considers that the pathogenesis of androgenic alopecia is complex and is caused by the combined action of a plurality of factors, including polygenic genetic factors, androgen metabolism factors, inflammation of the surrounding environment of hair follicles, various growth factors and cytokines existing in the hair follicles and the surrounding tissues, mental factors, life and diet factors, environmental factors, age and the like.

Methods of treating androgenic alopecia in the prior art include surgical and pharmaceutical treatments. The operation treatment comprises scalp dilatation, hair transplantation and the like, but has the defects of high cost, great difficulty, easy sore mark and the like, and the original hair can still lose hair. The medicine treatment comprises western medicine treatment and traditional Chinese medicine treatment. The western medicine treatment mainly adopts external chemical minoxidil lotion and oral finasteride, but minoxidil reports adverse reactions such as mild dermatitis of scalp, dizziness, irritation allergy, facial and limb hirsutism and the like, and minoxidil is marketed as antihypertensive medicine in the last 70 th century, and if the minoxidil is used carelessly, serious side effects can be caused; finasteride is a type ii 5-alpha reductase inhibitor that inhibits 5-alpha reductase, thereby reducing DHT levels in serum and scalp, but it can cause sexual dysfunction and psychological problems. Alopecia in traditional Chinese medicine also has some problems: the traditional Chinese medicine has complex syndrome differentiation and type classification, and clinical syndrome differentiation has no unified standard; the clinical curative effect has no obvious breakthrough in the aspect of hair growth, and particularly has unsatisfactory curative effect after thinning hair follicles with long disease course; meanwhile, most researches are only stopped at the summary of clinical experience, the intensive discussion of modern medical experiments is lacking, and many prescriptions are only suitable for patients with specific physique and illness, and have strong limitation and low universal suitability.

Therefore, there is an urgent need to develop a safe, efficient, low-cost medicament or product for promoting hair growth or alleviating hair loss.

Disclosure of Invention

In view of the above, it is desirable to provide a use of lactic acid and its derivatives for promoting hair growth and alleviating hair loss.

Use of lactic acid and derivatives thereof for the preparation of a composition for promoting hair growth and alleviating androgenic alopecia, wherein the composition comprises the lactic acid and derivatives thereof as the sole active ingredients.

Further, in the above application, the derivative of lactic acid is any one of the following chemical substances:

ethyl lactate and butyl lactate, potassium, sodium, zinc, ferrous, magnesium, calcium salts of lactic acid.

Further, in the above application, the composition further comprises a pharmaceutically acceptable carrier and an auxiliary material.

Further, the above application, wherein the carrier is one or more of distilled water, a tincture matrix, a paste matrix, an emulsion matrix, a patch matrix, a spray matrix and a film forming material.

Further, in the above application, the composition is an external preparation, and the external preparation is any one of a shampoo, a hair rinse, a hair conditioner, a lotion, an essence, an ointment, a gel, a patch, a tincture, and a spray.

Further, in the above application, the auxiliary material is one or more of preservative, humectant and flavoring agent.

Further, in the above application, the tincture matrix is one or more of ethanol, n-butanol, propylene glycol, glycerol, ethylene glycol, pentaerythritol and neopentyl glycol.

Further, in the above application, the ointment base is one or more of sesame oil, beeswax, spermaceti, wool ointment, vaseline, liquid paraffin, solid paraffin, silicone oil, sodium carboxymethylcellulose and polyethylene glycol.

Further, in the above application, the emulsion matrix is one or more of stearic acid, sodium dodecyl sulfate, tween-80, span-80, tween-20 and span-60 glyceryl monostearate.

Further, in the above application, the patch matrix is one or more of rosin, zinc oxide and vegetable oil.

Further, the above application, wherein the aerosol base is any one of tetrafluoroethane, heptafluoropropane and difluoroethane.

Further, in the above application, the film forming material is any one of polyvinyl alcohol 500, polyvinyl alcohol 1500 and acrylic resin.

Further, in the above application, the preservative is one or more of phenoxyethanol, benzyl alcohol, sodium benzoate, sodium sorbate, sorbic acid, 1, 2-pentanediol and 1, 2-hexanediol.

Further, in the above application, the humectant is one or more of glycerol, butanediol, polyethylene glycol, propylene glycol, hexanediol, xylitol, polypropylene glycol, and sorbitol.

Further, in the above application, the flavoring agent is one or more of orange peel oil, peppermint oil, cinnamon water, citric acid, banana essence, pineapple essence and lavender essence.

The experiment research proves that the lactic acid and the derivatives thereof have the effect of inhibiting the androgenetic alopecia, so that the lactic acid and the derivatives thereof have new application and industrial application value, and the result can be applied to the medical clinical practice of promoting hair growth and inhibiting the androgenetic alopecia, is used for developing medicines and cosmetics for promoting hair growth, has potential economic and social benefits, and meets the demands of people on alopecia prevention products.

Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following description will briefly explain the drawings needed in the embodiments of the present application, and it is obvious that the drawings described below are only some embodiments of the present application, and that other drawings can be obtained according to these drawings without inventive effort for a person skilled in the art.

FIG. 1 is a graph showing the effect of different drugs provided in the examples of the present invention on hair growth treatment of androgenic alopecia mice;

FIG. 2 shows the growth of hair follicle cells in the back skin of mice after treatment of androgenic alopecia mice with different drugs according to the present invention.

Detailed Description

The following detailed description of the present invention will provide further understanding of the objects, features and advantages of the present invention by way of example. Several embodiments of the invention are presented in the examples. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

Example 1: preparation of 10mg/ml lactic acid and its derivatives

The material consists of the following raw materials in percentage by mass: 2.5% of 1, 2-propanediol, 0.25% of sodium sorbate, 0.05% of lactic acid, 0.95% of sodium lactate, 0.3% of lavender essence and the balance of distilled water.

The preparation method comprises the following steps:

(1) And (3) taking half of distilled water and sodium sorbate, stirring and mixing, heating to 70 ℃ to obtain a material A, and mixing and stirring lavender essence, 25% of distilled water and 1, 2-propanediol to obtain a material B.

(2) And stirring and uniformly mixing the material A and the material B at 40 ℃ to obtain a material C.

(3) And uniformly mixing the rest distilled water, lactic acid and sodium lactate to maintain the PH between 5.1 and 6.9, thus obtaining a material D.

(4) And (3) uniformly mixing the materials C and D under the condition of 25 ℃ by ultrasonic waves to obtain the composition of the lactic acid and the derivative with the concentration of 10 mg/ml.

Example 2: preparation of a composition of 20mg/ml lactic acid and its derivatives

The material consists of the following raw materials in percentage by mass: 2.5% of 1, 2-propanediol, 0.25% of sodium sorbate, 0.10% of lactic acid, 1.9% of sodium lactate, 0.3% of lavender essence and the balance of distilled water.

The preparation method comprises the following steps:

(4) And (3) uniformly mixing the materials C and D under the condition of 25 ℃ by ultrasonic waves to obtain the composition of the lactic acid and the derivatives thereof with the concentration of 20 mg/ml.

Example 3: preparation of 5mg/ml lactic acid and derivative composition

The material consists of the following raw materials in percentage by mass: 2.5% of 1, 2-propanediol, 0.25% of sodium sorbate, 0.025% of lactic acid, 0.475% of sodium lactate, 0.3% of lavender essence and the balance of distilled water.

The preparation method comprises the following steps:

(2) Stirring and mixing the material A and the material B at 40 ℃ to obtain a material C

Comparative example 1: preparation of 10mg/ml lactic acid solution

Taking 50ml of distilled water and 1000mg of lactic acid according to volume fractions, carrying out ultrasonic mixing by using an ultrasonic instrument, adding enough distilled water after uniformly mixing to ensure that the total volume of the solution reaches 100ml, and carrying out ultrasonic mixing to obtain 10mg/ml of lactic acid solution.

Comparative example 2: preparation of 10mg/ml sodium lactate solution

Taking 50ml of distilled water and 1000mg of sodium lactate according to volume fraction, carrying out ultrasonic mixing by using an ultrasonic instrument, adding enough distilled water after uniformly mixing to ensure that the total volume of the solution reaches 100ml, and carrying out ultrasonic mixing to obtain 10mg/ml of sodium lactate solution.

Example 4: PH measurement of different compositions

The compositions of examples 1 to 3, and the compositions of comparative examples 1 to 2 were each measured for pH using a pH meter, and the results are shown in Table 1.

TABLE 1 PH of different compositions

From the experimental results, the pH values of the pure lactic acid and the sodium lactate solution deviate from neutral values, and the lactic acid and the sodium lactate are mixed to prepare neutral medicaments, so that the irritation of the medicaments to scalp is reduced.

Example 5: experiment of the effects of lactic acid and its derivatives on the growth of androgen-induced alopecia mice

56C 57BL/6 mice were randomly assigned to androgen alopecia model group (negative control group), normal group, minoxidil tincture group (positive control group), 20mg/ml lactic acid and its derivative group, 10mg/ml lactic acid and its derivative group, 5mg/ml lactic acid and its derivative group, 10mg/ml lactic acid solution group, 8 each. All mice are coated on the backs of the mice by using paraffin wax and rosin in equal proportion in the day before administration, the mixture is uncovered after cooling, the hairs in the back area (2 cm multiplied by 3 cm) of the mice are removed, 0.1ml of testosterone solution is coated in the dehairing area of 0.5 ml per day except that of the normal group, and an androgenic alopecia mouse model is constructed.

The dosing regimen was as follows:

normal group: 0.2ml physiological saline is smeared daily, and the administration is carried out twice a day in the morning and evening.

Androgen alopecia model group: 0.2ml physiological saline is smeared daily, and the administration is carried out twice a day in the morning and evening.

Minoxidil tincture group: 0.2ml of 2% minoxidil tincture is applied daily and is administrated twice a day in the morning and evening.

20mg/ml lactic acid and derivatives group: the composition containing 20mg/ml lactic acid and its derivatives is applied at a dose of 0.2ml daily, and is administered twice a day in the morning and evening.

10mg/ml lactic acid and derivatives group: the composition containing 10mg/ml lactic acid and its derivatives is applied at a dose of 0.2ml daily, and is administered twice a day in the morning and evening.

5mg/ml lactic acid and derivatives group: the composition containing 5mg/ml lactic acid and its derivatives is applied at a dose of 0.2ml daily, and is administered twice a day in the morning and evening.

Group of 10mg/ml lactic acid solution: the preparation is applied with 10mg/ml lactic acid solution 0.2ml daily, and is administered twice a day in the morning and evening.

For all mice given 24 days continuously, photographs were taken on days 1, 8, 11, 15, 18, and 24 of the mice administration, respectively, and the hair growth of the mice was observed, and the results are shown in fig. 2. 10 new hairs were randomly taken at the experimental area on days 15 and 24 of administration, measured using an electronic digital vernier caliper and recorded, and the results are shown in table 2. And all new hairs in the experimental area were shaved with a razor Mao Qixiao heart on the last day of dosing, and the complete measurements were collected and recorded using an electronic balance weighing ten thousandth, and the results are shown in table 3. The growth of hair follicle cells was observed by HE staining the back skin of the mice, and the total number of hair follicle cells was counted in the same horizontal plane of the skin cross section, and the results are shown in Table 4. Taking the skin of the rest mice, homogenizing the tissues, centrifuging for 10min at 3000r/min, taking the supernatant, and sub-packaging and freezing. The KGF, VEGF, DHT factor content in the skin of the mice was determined strictly according to the methods of the KGF, VEGF and DHT Elisa kit, and the results are shown in tables 5, 6 and 7.

Table 2: effect on the length of neonatal hair in androgenic alopecia mice

Note that: in contrast to the androgenic alopecia model group, ^* represents p<0.05, has the significance of statistical difference, ^** represents p<0.01, statistically significant differences.

From the experimental results of fig. 1 and table 2, it can be seen that: as can be seen from the hair length, the new-born hair growth of mice can be slowed down by applying testosterone solution, and the minoxidil tincture remarkably increases the hair growth rate (p < 0.01) on the 24 th day after the application of the drug treatment, so that the hair length is longer; the anti-5 mg/ml lactic acid and the derivative and 10mg/ml lactic acid and the derivative obviously accelerate the growth of the hair of mice with androgenic alopecia groups (p < 0.05), obviously increase the hair length, and the 10mg/ml lactic acid solution causes stimulation to the skin of the mice due to the deviation of the pH value from neutrality, so that the hair growth of the mice is slow.

Table 3: influence on the weight of new hair in androgenic alopecia mice

Note that: in contrast to the androgenic alopecia model group, ^* p<0.05， ^** p<0.01。

from the experimental results in table 3, it can be seen that: the comparison of the normal group and the model group shows that testosterone is applied to reduce the weight of the hair of the mice, an androgen alopecia mouse model is successfully established, after administration treatment, minoxidil tincture and 10mg/ml lactic acid and derivatives thereof are used for relieving the influence of androgen alopecia, the weight of the new hair of the mice is remarkably increased (p < 0.01), and the effect of 20mg/ml lactic acid and derivatives thereof is less than that of 10mg/ml lactic acid and derivatives thereof, but is also remarkably different from that of the androgen alopecia model group (p < 0.05), so that the effect of the anti-androgen alopecia drug for treating androgen alopecia is equivalent to that of minoxidil tincture. 10mg/ml lactic acid solution resulted in reduced hair growth area and reduced hair weight due to irritation.

Table 4: effect on the number of hair follicles in the dorsal skin of mice

from the experimental results in table 4, it can be seen that: modeling with testosterone solution significantly reduced the number of hair follicles in mice in model group (p <0.01 compared to model group), significantly increased the number of dorsal skin hair follicles in mice in minoxidil tincture group (p < 0.01), significantly increased the number of hair follicles in dorsal skin in mice in 10mg/ml lactic acid and derivatives thereof (p < 0.01), indicating that lactic acid and derivatives thereof can alleviate symptoms of androgenic alopecia, and promote hair growth.

Table 5: dihydrotestosterone (DHT) content in mouse skin

Dihydrotestosterone (DHT) can be exuded from capillaries around hair papilla cells or directly generated by hair papilla cells, and the highly active dihydrotestosterone is combined with androgen receptor to act on hair follicle, induce it to rapidly enter the catastrophe stage, and is miniaturized to cause hair loss. From the experimental results in table 5, it can be seen that: after modeling with testosterone solution, the dihydrotestosterone content in mice of model group was significantly increased (p < 0.01), and after treatment with lactic acid and its derivatives, the dihydrotestosterone level in mice was significantly decreased (p < 0.05), indicating that lactic acid and its derivatives can effectively decrease dihydrotestosterone content, thereby reducing hair loss and inhibiting androgenic alopecia symptoms.

Table 6: keratinocyte Growth Factor (KGF) content in mouse skin

Note that: p <0.05, p <0.01 compared to androgenic alopecia model group

Keratinocyte growth factor is a factor secreted by keratinocytes and promotes the expression of epithelial cells and proliferation and differentiation of keratinocytes. From the experimental results in table 6, it can be seen that: the keratinocyte growth factor concentration in the skin of mice of the androgenic alopecia model group was significantly reduced compared to the normal group (p < 0.01). After drug treatment, the keratinocyte growth factor content of 10mg/ml lactic acid and its derivatives and minoxidil tincture group mice was significantly increased (p < 0.01), which suggests that lactic acid and its derivatives promote hair growth of mice by increasing keratinocyte growth factor secretion of mice.

Table 7: vascular Endothelial Growth Factor (VEGF) content in mouse skin

Note that: p <0.05, p <0.01 compared to androgenic alopecia model group

Vascular endothelial cell growth factor (VEGF) acts on vascular endothelial cells in the dermis layer by paracrine, induces increased microvascular synthesis in localized areas of the skin, provides nutrients for hair follicle cells, and promotes hair follicle growth. From the experimental results in table 7, it can be seen that: vascular endothelial growth factor concentration was significantly reduced in the skin of mice in the androgenic alopecia model group compared to the normal group (p < 0.01). After the application of the drug treatment, the content of the keratinocyte growth factor of the mice in the minoxidil tincture group and the lactic acid and the derivatives thereof with 10mg/ml are obviously increased (p < 0.01), which indicates that the anti-androgenic alopecia drug can promote the hair growth of the mice by increasing the secretion of the vascular endothelial cell growth factor of the mice.

Experimental results show that lactic acid and derivatives can effectively inhibit symptoms of androgenic alopecia mice and promote hair growth. When the total amount of the lactic acid and the derivative is administrated transdermally at a daily dose of 50-200 mg/kg, the symptom of androgenic alopecia can be relieved, and compared with an androgenic alopecia model group, the effect is obviously different, and is equivalent to the effect of minoxidil which is the most main antiandrogenic medicine at present.

The experiment research proves that the lactic acid and the derivatives thereof have the effect of inhibiting androgenetic alopecia, so that the lactic acid and the derivatives thereof have new application and industrial application value, and the result can be applied to the medical clinical practice of promoting hair growth, is used for developing medicines and cosmetics for promoting hair growth, has potential economic and social benefits, and meets the demands of people on alopecia prevention products.

In the description of the present specification, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

The foregoing examples illustrate only a few embodiments of the invention and are described in detail herein without thereby limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims

1. Use of lactic acid and derivatives thereof for the preparation of a composition for promoting hair growth and alleviating androgenic alopecia, wherein the composition comprises the lactic acid and derivatives thereof as the sole active ingredients.

2. The use according to claim 1, wherein the derivative of lactic acid is any one of the following chemicals:

3. The use according to claim 1, wherein the composition further comprises a pharmaceutically acceptable carrier and an adjuvant.

4. The use according to claim 3, wherein the carrier is one or more of distilled water, a tincture matrix, a paste matrix, an emulsion matrix, a patch matrix, a spray matrix and a film forming material.

5. The use according to claim 3, wherein the composition is an external preparation, which is any one of a shampoo, a hair rinse, a conditioner, a lotion, a essence, an ointment, a gel, a patch, a tincture, and a spray.

6. The use according to claim 3, wherein the adjuvant is one or more of a preservative, a humectant and a flavouring.

7. The use according to claim 4, wherein the tincture matrix is one or more of ethanol, n-butanol, propylene glycol, glycerol, ethylene glycol, pentaerythritol and neopentyl glycol.

8. The use according to claim 4, wherein the ointment base is one or more of sesame oil, beeswax, spermaceti, lanolin, vaseline, liquid paraffin, solid paraffin, silicone oil, sodium carboxymethylcellulose and polyethylene glycol.

9. The use according to claim 4, wherein the emulsion base is one or more of stearic acid, sodium dodecyl sulfate, tween-80, span-80, tween-20, span-60 glyceryl monostearate.

10. The use according to claim 4, wherein the patch matrix is one or more of rosin, zinc oxide, vegetable oil.

11. The use according to claim 4, wherein the aerosol base is any one of tetrafluoroethane, heptafluoropropane and difluoroethane.

12. The use according to claim 4, wherein the film-forming material is any one of polyvinyl alcohol 500, polyvinyl alcohol 1500, acrylic resin.

13. The use according to claim 6, wherein the preservative is one or more of phenoxyethanol, benzyl alcohol, sodium benzoate, sodium sorbate, sorbic acid, 1, 2-pentanediol, and 1, 2-hexanediol.

14. The use according to claim 6, wherein the humectant is one or more of glycerol, butylene glycol, polyethylene glycol, propylene glycol, hexylene glycol, xylitol, polypropylene glycol, sorbitol.

15. The use according to claim 6, wherein the flavouring is one or more of orange peel oil, peppermint oil, cinnamon water, citric acid, banana essence, pineapple essence and lavender essence.