Hair rising and protecting series composition for treating alopecia as well as preparation method and application of hair rising and protecting series composition

Abstract

The invention discloses a hair-raising and protecting series composition for treating alopecia as well as a preparation method and application thereof, and relates to the technical field of medicines, and the composition is prepared from minoxidil, propylene glycol, menthol, betaine, an amino acid compound, glycyrrhizic acid, tocopheryl acetate, hinokiol, pyridoxine, ethanol and purified water. The preparation method comprises the following steps: mixing propylene glycol, minoxidil, menthol and ethanol, adding hinokiol, mixing, adding pyridoxine, an amino acid compound and betaine, mixing, adding tocopheryl acetate and glycyrrhizic acid, and mixing. According to the minoxidil composition, the absorption rate of minoxidil can be increased, the drug resistance of the minoxidil composition after being used for a long time is reduced, and the treatment effect of the minoxidil composition on various types of alopecia patients is effectively improved. The invention solves the problem that minoxidil and hinokiol are difficult to dissolve and easy to separate out, has the advantages of good absorption effect and lasting alopecia treatment effect, effectively improves newborn hair quality and scalp greasy state, and brings new dawn to alopecia patients.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and particularly relates to a hair-raising and hair-protecting series composition for treating hair loss and a preparation method thereof. Background Art

[0002] Common causes of hair loss include hormonal changes, genetics, malnutrition, stress, folliculitis, endocrine disorders, and physical and chemical damage. The main symptoms of hair loss are greasy hair, as if oiled, or dry, frizzy hair, lack of luster, clinging yellowish scales, or flaky gray scales, and itching. In men, hair loss primarily affects the forehead and top of the head, with the hairline and temples shifting upward. The hair on the forehead and top of the head becomes sparse, yellowing, and softening, eventually leaving the forehead somewhat fuzzy or completely bald.

[0003] Types of hair loss include androgenic alopecia, alopecia areata, hereditary alopecia, neurotic alopecia, chemical alopecia, physical alopecia, nutritional alopecia, obesity-related alopecia, and infectious alopecia, among which androgenic alopecia has the highest incidence. According to statistics, approximately 75% of men will experience some degree of androgenic alopecia before the age of 30, and approximately 70% of menopausal women will experience androgenic alopecia. The main clinical manifestations of androgenic alopecia are the gradual receding of the hairline, forming an M-shape, followed by the appearance of an O-shaped hair loss ring on the top of the head, and the M+O type. As the hairline recedes, the hair loss ring on the top of the head connects to form a horseshoe-shaped U-shape, also known as the Mediterranean type.

[0004] Minoxidil liniment is a commonly used product for treating hair loss. It can treat various types of hair loss, including androgenic alopecia, seborrheic alopecia, and postpartum hair loss. Minoxidil is a peripheral vasodilator that improves microcirculation around hair follicles and increases blood flow to the skin. Long-term topical application can stimulate hair growth in patients with male pattern baldness and alopecia areata. However, minoxidil has some drawbacks. Its percutaneous absorption rate is very low, approximately 2%. As a result, most of the active ingredient remains on the scalp. Chemical reactions ultimately form large crystalline particles that cannot be absorbed by the scalp, severely impacting the effectiveness of the treatment. Furthermore, patients who initially use minoxidil experience rapid hair loss, while long-term use can lead to diminished or rebound effects. Ninety-five percent of patients experiencing hair loss followed by new growth experience a period of hair loss when using minoxidil liniment, leading some to abandon treatment, believing it is ineffective and causing further hair loss. Some patients have also reported that the new hair that grows after using minoxidil is soft and dull in color, often accompanied by adverse reactions such as dry scalp, scaling, itching, and redness. Furthermore, long-term use can lead to drug tolerance, weakening or even rendering the treatment ineffective. When using minoxidil for hair loss, hair growth not only occurs in the affected area, but some patients also experience increased hair growth and growth in other areas of the body. This is because minoxidil is partially absorbed through the skin and enters the bloodstream, circulating throughout the body, causing similar symptoms, adding further trouble for some patients.

[0005] CN115475168B, entitled "Minoxidil-Containing Pharmaceutical Composition, Preparation Method, and Use thereof," discloses a pharmaceutical composition comprising the following active ingredients: minoxidil or a pharmaceutically acceptable salt thereof, and tocopherol acetate; these active ingredients are formulated together or separately, used in combination, or used simultaneously. The pharmaceutical composition has significant efficacy in treating androgenic alopecia. Minoxidil and tocopherol acetate exhibit a synergistic effect, achieving a 1+1>2 effect. Minoxidil and tocopherol acetate, when delivered via ethosome nanocarriers, exhibit higher skin permeation and retention in hair follicles, demonstrating improved follicle targeting. The pharmaceutical composition in this patent includes minoxidil, tocopherol acetate, and lecithin. However, lecithin is an oily substance that can hinder minoxidil absorption, and tocopherol acetate is merely an antioxidant, lacking a significant effect on hair growth. The remaining substances are merely conventional additives with no substantial effects. Therefore, compared to minoxidil alone, its effect on hair growth is less pronounced.

[0006] Therefore, improving the absorption rate of minoxidil and overcoming drug resistance caused by long-term use have become the key to research and development, and developing a product that effectively treats hair loss based on market demand has become the top priority. Summary of the Invention

[0007] The purpose of the present invention is to solve the above problems and to provide a hair-lifting and hair-protecting series composition for treating hair loss, as well as a preparation method and application thereof.

[0008] The present invention provides a hair-promoting and hair-protecting series composition for treating hair loss. The composition comprises, by weight, 30-800 parts of minoxidil, 300-4000 parts of propylene glycol, 8-50 parts of menthol, 2-30 parts of betaine, 2-30 parts of an amino acid complex, 1-25 parts of glycyrrhetinic acid, 1-20 parts of tocopheryl acetate, 0.5-15 parts of hinokitiol, 0.5-15 parts of pyridoxine, 900-5000 parts of ethanol, and 200-1800 parts of purified water.

[0009] Furthermore, the composition is composed of 50-500 parts of minoxidil, 1500-3500 parts of propylene glycol, 15-30 parts of menthol, 6-18 parts of betaine, 6-18 parts of amino acid complex, 3-15 parts of glycyrrhetinic acid, 2-12 parts of tocopheryl acetate, 1-8 parts of hinokitiol, 1-8 parts of pyridoxine, 1800-4000 parts of ethanol and 400-1500 parts of purified water.

[0010] Furthermore, the composition is composed of 250-320 parts of minoxidil, 2700-3200 parts of propylene glycol, 18-25 parts of menthol, 8-14 parts of betaine, 8-14 parts of amino acid complex, 5-10 parts of glycyrrhetinic acid, 4-8 parts of tocopheryl acetate, 2-5 parts of hinokitiol, 2-5 parts of pyridoxine, 2400-3000 parts of ethanol and 800-1200 parts of purified water.

[0011] Furthermore, the amino acid complex is composed, by weight, of 10-80 parts of glycine, 2-50 parts of serine, 2-40 parts of glutamic acid, 2-35 parts of aspartic acid, 1-40 parts of leucine, 1-40 parts of alanine, 1-40 parts of lysine, 1-20 parts of arginine, 1-20 parts of tyrosine, 1-20 parts of phenylalanine, 1-20 parts of threonine, 1-20 parts of proline, 1-20 parts of valine, 1-20 parts of isoleucine, 1-20 parts of histidine, 1000-5000 parts of butanediol, and 4000-9500 parts of water.

[0012] Furthermore, the amino acid complex is composed, by weight, of 18-40 parts of glycine, 8-30 parts of serine, 8-20 parts of glutamic acid, 5-15 parts of aspartic acid, 4-15 parts of leucine, 2-10 parts of alanine, 2-10 parts of lysine, 1-10 parts of arginine, 1-10 parts of tyrosine, 1-10 parts of phenylalanine, 1-10 parts of threonine, 1-10 parts of proline, 1-10 parts of valine, 1-10 parts of isoleucine, 1-10 parts of histidine, 2500-3500 parts of butanediol, and 6500-8500 parts of water.

[0013] Furthermore, the amino acid complex is composed, by weight, of 22-30 parts of glycine, 10-20 parts of serine, 10-15 parts of glutamic acid, 7-10 parts of aspartic acid, 6-10 parts of leucine, 3-6 parts of alanine, 3-6 parts of lysine, 2-5 parts of arginine, 2-5 parts of tyrosine, 2-5 parts of phenylalanine, 2-5 parts of threonine, 2-5 parts of proline, 2-5 parts of valine, 2-4 parts of isoleucine, 1-3 parts of histidine, 2800-3200 parts of butanediol, and 6700-8200 parts of water.

[0014] The preparation method of a hair-raising and hair-protecting series composition for treating hair loss of the present invention: (1) Weigh 30-800 parts of minoxidil, 300-4000 parts of propylene glycol, 8-50 parts of menthol, 2-30 parts of betaine, 2-30 parts of amino acid complex, 1-25 parts of glycyrrhetinic acid, 1-20 parts of tocopheryl acetate, 0.5-15 parts of hinokitiol, 0.5-15 parts of pyridoxine, 900-5000 parts of ethanol and 200-1800 parts of purified water according to weight and set aside; (2) Add 300-4000 parts of propylene glycol to a liquid preparation tank, add 15-400 parts of minoxidil and 8-50 parts of menthol while stirring, stir for 5-20 minutes, then add 500-3800 parts of ethanol and 15-400 parts of minoxidil in this order, stir for 1-10 minutes, then add 150-1500 parts of purified water, stir for 2-15 minutes, and obtain mixture ①, which is set aside; (3) Take 100-300 parts of ethanol and add 0.5-15 parts of hinokitiol to a beaker, stir for 1-10 minutes, and treat with a reduced pressure ultrasonic device for 2-15 minutes to obtain a mixture ②, which is set aside; (4) Take 50-300 parts of purified water to a liquid preparation tank, add 0.5-15 parts of pyridoxine, 2-30 parts of amino acid complex, and 2-30 parts of betaine while stirring, and stir at 260 rpm for 5-30 minutes to obtain mixture ③, which is set aside; (5) Add 300-900 parts of ethanol to a liquid preparation tank, add 1-20 parts of tocopherol acetate while stirring, stir at 150 rpm for 2-15 minutes, then add 1-25 parts of glycyrrhetinic acid, stir at 300 rpm for 5-30 minutes to obtain a mixture ④, which is set aside; (6) Add mixture ② to the liquid preparation tank, divide mixture ③ into three equal parts, add one part first and stir for 2-15 minutes, then add the second part and stir for 2-15 minutes, and finally add the third part and stir for 5-30 minutes to obtain mixture ⑤, which is set aside; (7) Add mixture ④ to the liquid preparation tank, turn on the double-screw stirring device, set the speed to 500 rpm, and add mixture ① by spraying, while controlling the feeding speed to 10 Hz. After the addition is completed, continue stirring for 2-15 minutes to obtain mixture ⑥, which is set aside; (8) Divide mixture ⑤ and mixture ⑥ into two equal parts, first add one part of mixture ⑥ to the liquid preparation tank, slowly add one part of mixture ⑤, stir for 5-30 minutes, then add another part of mixture ⑥, stir for 5-30 minutes, and finally add the remaining part of mixture ⑤ to the mixing tank, stir for 10-50 minutes, and set the stirring speed to 300 rpm; after the total mixing, filter the materials with a 100-mesh sieve to obtain the composite material.

[0015] Mixture ② is a fat-soluble solution. A small amount of mixture ③ (water-soluble solution) is added first to avoid precipitation of substances in the two phases. By adding small amounts multiple times, the components can be distributed more evenly during the mixing process, reducing the stratification phenomenon caused by differences in component specific gravity and particle size.

[0016] The present invention discloses an application of a hair-promoting and hair-protecting series composition for treating hair loss. The composition is used to prepare a product for treating hair loss and promoting hair growth.

[0017] The present invention provides a series of hair-raising and hair-protecting compositions for treating hair loss and a preparation method thereof. The various substances in the compositions synergize with each other, not only improving the absorption rate of minoxidil but also reducing drug resistance with long-term use of the compositions, effectively enhancing the therapeutic efficacy of the products for patients with various types of hair loss. Through efficient dissolution and formulation methods, the compositions of the present invention address the difficulties of dissolving and easily precipitating minoxidil and hinokitiol, resulting in compositions with excellent absorption and long-lasting hair loss treatment effects. Furthermore, they effectively improve the quality of newly grown hair and the oiliness of the scalp, bringing new hope to patients with hair loss. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is a microscopic image of composition 1 after dissolution (magnification 400 times); Figure 2 This is a microscopic image of composition 2 after dissolution (magnification 400 times); Figure 3 This is a microscopic image of composition 3 after dissolution (magnification 200 times); Figure 4 This is a microscopic image of composition 4 after dissolution (magnification 400 times); Figure 5 This is a microscopic image of composition 5 after dissolution (magnification 400 times); Figure 6 This is a graph showing the hair growth of mice from the day of hair loss to the 42nd day of drug administration; Figure 7The figure shows the effect of the composition on hair length in androgenic alopecia model mice; Figure 8 The figure shows the effect of the composition on the hair weight of androgenic alopecia model mice. DETAILED DESCRIPTION

[0019] In order to make the objectives, technical solutions and advantages of the embodiments of the present invention more clearly understood, the spirit of the contents disclosed in the present invention will be described in detail below. After understanding the embodiments of the contents of the present invention, any technician in the relevant technical field can change and modify the contents of the present invention based on the techniques taught by the contents of the present invention without departing from the spirit and scope of the contents of the present invention.

[0020] The exemplary embodiments of the present invention and the description thereof are used to explain the present invention but are not intended to limit the present invention.

[0021] Example 1 Preparation method of a hair-raising and hair-protecting series composition for treating hair loss The composition consists of minoxidil 300g, propylene glycol 3000g, menthol 22.0g, betaine 10g, amino acid complex 10g, glycyrrhetinic acid 7.5g, tocopheryl acetate 5.5g, hinokitiol 4g, pyridoxine 4g, ethanol 2620g, and purified water 1017g; The amino acid complex consists of 0.025g of glycine, 0.014g of serine, 0.013g of glutamic acid, 0.008g of aspartic acid, 0.007g of leucine, 0.0045g of alanine, 0.004g of lysine, 0.004g of arginine, 0.0035g of tyrosine, 0.0035g of phenylalanine, 0.003g of threonine, 0.003g of proline, 0.003g of valine, 0.003g of isoleucine, 0.0015g of histidine, 3g of butanediol and 6.9g of water.

[0022] The preparation method of the composition comprises the following steps: (1) Accurately weigh all the raw materials according to the above formula and set aside; (2) Take 3000g of propylene glycol and put it into the liquid preparation tank, then add 1800g of ethanol, add 300g of minoxidil while stirring, stir for 30min, then add 900g of purified water and stir for 20min to obtain mixture ①, set aside.

[0023] (3) Take 117g of purified water and put it into the liquid preparation tank. Add 4g of pyridoxine, 4g of amino acid complex and 10g of betaine while stirring. Stir at 260rpm for 10min to obtain mixture ②, which is set aside.

[0024] (4) Take 820 g of ethanol and put it into a liquid preparation tank. Add 5.5 g of tocopherol acetate, 22.0 g of menthol, 7.5 g of glycyrrhetinic acid, and 4 g of cypress phenol under stirring. Stir at 300 rpm for 10 min to obtain mixture ③, which is set aside.

[0025] (5) Add mixtures ② and ③ to the liquid preparation tank and stir for 10 minutes. Then add mixture 1 and stir for 30 minutes at a stirring speed of 300 rpm. Filter the mixed materials through a 100-mesh sieve to obtain the composite material.

[0026] Example 2 Preparation method of a hair-raising and hair-protecting series composition for treating hair loss The composition consists of minoxidil 300g, propylene glycol 3000g, menthol 22.0g, betaine 10g, amino acid complex 10g, glycyrrhetinic acid 7.5g, tocopheryl acetate 5.5g, hinokitiol 4g, pyridoxine 4g, ethanol 2620g, and purified water 1017g; The amino acid complex consists of 0.025g of glycine, 0.014g of serine, 0.013g of glutamic acid, 0.008g of aspartic acid, 0.007g of leucine, 0.0045g of alanine, 0.004g of lysine, 0.004g of arginine, 0.0035g of tyrosine, 0.0035g of phenylalanine, 0.003g of threonine, 0.003g of proline, 0.003g of valine, 0.003g of isoleucine, 0.0015g of histidine, 3g of butanediol and 6.9g of water.

[0027] The preparation method of the composition comprises the following steps: (1) Accurately weigh all the raw materials according to the above formula and set aside; (2) Take 3000g of propylene glycol and put it into the liquid preparation tank. Add 150g of minoxidil and 22.0g of menthol while stirring. Stir for 10 minutes. Then add 1800g of ethanol and 150g of minoxidil in this order. Stir for 2 minutes. Then add 900g of purified water and stir for 5 minutes to obtain mixture ①. Set aside.

[0028] (3) Take 200g of ethanol and put it into a beaker. Add 4g of cypress phenol and stir for 2min. Treat with a reduced pressure ultrasonic device for 5min to obtain mixture ②. Set aside.

[0029] (4) Take 117 g of purified water and put it into the liquid preparation tank. Add 4 g of pyridoxine, 4 g of amino acid complex, and 10 g of betaine while stirring. Stir at 260 rpm for 10 min to obtain mixture ③, which is set aside.

[0030] (5) Take 620 g of ethanol and put it into the liquid preparation tank. Add 5.5 g of tocopherol acetate while stirring. Stir at 150 rpm for 5 min (low speed helps dissolve and avoid material loss). Then add 7.5 g of glycyrrhetinic acid and stir at 300 rpm for 10 min to obtain mixture ④, which is set aside.

[0031] (6) Add mixture ② to the liquid preparation tank, divide mixture ③ into three equal parts, add one part first and stir for 5 minutes, then add the second part and stir for 5 minutes, and finally add the third part and stir for 10 minutes to obtain mixture ⑤, which is set aside.

[0032] (7) Add mixture ④ into the liquid preparation tank, turn on the double-screw stirring device, set the speed to 500 rpm, add mixture ① by spraying, and control the feeding speed to 10 Hz. After the addition is completed, continue stirring for 5 minutes to obtain mixture ⑥, which is set aside.

[0033] (8) Divide mixture ⑤ and mixture ⑥ into two equal parts. First, add one part of mixture ⑥ to the liquid preparation tank, then slowly add one part of mixture ⑤ and stir for 10 minutes. Then add another part of mixture ⑥ and stir for 10 minutes. Finally, add the remaining part of mixture ⑤ to the mixing tank and stir for 20 minutes. The stirring speed is set to 300 rpm. After the total mixing, the materials are filtered through a 100-mesh sieve to obtain the composite material.

[0034] Example 3 Preparation method of a hair-raising and hair-protecting series composition for treating hair loss The composition consists of 120g of minoxidil, 1200g of propylene glycol, 22g of menthol, 10g of betaine, 10g of amino acid complex, 7.5g of glycyrrhetinic acid, 5.5g of tocopheryl acetate, 4g of hinokitiol, 4g of pyridoxine, 4420g of ethanol and 1197g of purified water.

[0035] The amino acid complex consists of 0.025g of glycine, 0.014g of serine, 0.013g of glutamic acid, 0.008g of aspartic acid, 0.007g of leucine, 0.0045g of alanine, 0.004g of lysine, 0.004g of arginine, 0.0035g of tyrosine, 0.0035g of phenylalanine, 0.003g of threonine, 0.003g of proline, 0.003g of valine, 0.003g of isoleucine, 0.0015g of histidine, 3g of butanediol and 6.9g of water.

[0036] The preparation method of the composition comprises the following steps: (1) Accurately weigh all the raw materials according to the above formula and set aside; (2) Take 1200g of propylene glycol and put it into the liquid preparation tank. Add 60g of minoxidil and 22.0g of menthol while stirring. Stir for 10 minutes. Then add 3600g of ethanol and 60g of minoxidil in this order. Stir for 2 minutes. Then add 1080g of purified water and stir for 5 minutes to obtain mixture ①. Set aside.

[0037] (3) Take 200g of ethanol and put it into a beaker. Add 4g of cypress phenol and stir for 2min. Treat with a reduced pressure ultrasonic device for 5min to obtain mixture ②. Set aside.

[0038] (4) Take 117 g of purified water and put it into the liquid preparation tank. Add 4 g of pyridoxine, 4 g of amino acid complex, and 10 g of betaine while stirring. Stir at 260 rpm for 10 min to obtain mixture ③, which is set aside.

[0039] (5) Take 620 g of ethanol and put it into the liquid preparation tank. Add 5.5 g of tocopherol acetate while stirring. Stir at 150 rpm for 5 min (low speed helps dissolve and avoid material loss). Then add 7.5 g of glycyrrhetinic acid and stir at 300 rpm for 10 min to obtain mixture ④, which is set aside.

[0040] (6) Add mixture ② to the liquid preparation tank, divide mixture ③ into three equal parts, add one part first and stir for 5 minutes, then add the second part and stir for 5 minutes, and finally add the third part and stir for 10 minutes to obtain mixture ⑤, which is set aside.

[0041] (7) Add mixture ④ into the liquid preparation tank, turn on the double-screw stirring device, set the speed to 500 rpm, add mixture ① by spraying, and control the feeding speed to 10 Hz. After the addition is completed, continue stirring for 5 minutes to obtain mixture ⑥, which is set aside.

[0042] (8) Divide mixture ⑤ and mixture ⑥ into two equal parts. First, add one part of mixture ⑥ to the liquid preparation tank, then slowly add one part of mixture ⑤ and stir for 10 minutes. Then add another part of mixture ⑥ and stir for 10 minutes. Finally, add the remaining part of mixture ⑤ to the mixing tank and stir for 20 minutes. The stirring speed is set to 300 rpm. After the total mixing, the materials are filtered through a 100-mesh sieve to obtain the composite material.

[0043] The minoxidil detection methods in the experimental examples of this application are all the minoxidil detection methods in Part II of the 2020 edition of the "Chinese Pharmacopoeia".

[0044] Experimental Example 4 Comparative experiment of different composition ingredients According to consumer feedback, minoxidil is a commonly used pharmaceutical preparation for treating male pattern baldness and alopecia areata, and is significantly more effective than conventional cosmetic products in treating hair loss. However, some patients experience poor results after prolonged use. A detailed experimental comparison was conducted with the product of the present invention, as detailed below. The results are shown in the table below.

[0045] Composition 1: minoxidil 300g, propylene glycol 3000g, ethanol 2620g, purified water 1017g.

[0046] Composition 2: minoxidil 300g, propylene glycol 3000g, tocopheryl acetate 5.5g, ethanol 2620g, purified water 1017g.

[0047] Composition 3: minoxidil 300g, propylene glycol 3000g, betaine 10g, amino acid complex 10g, glycyrrhetinic acid 7.5g, tocopheryl acetate 5.5g, pyridoxine 4g, ethanol 2620g, purified water 1017g.

[0048] Composition 4: minoxidil 300g, propylene glycol 3000g, betaine 10g, amino acid complex 10g, glycyrrhetinic acid 7.5g, tocopheryl acetate 5.5g, hinokitiol 4g, pyridoxine 4g, ethanol 2620g, purified water 1017g.

[0049] Composition 5: minoxidil 300g, propylene glycol 3000g, menthol 22.0g, betaine 10g, amino acid complex 10g, glycyrrhetinic acid 7.5g, tocopheryl acetate 5.5g, hinokitiol 4g, pyridoxine 4g, ethanol 2620g, purified water 1017g.

[0050] The raw material compositions of the above compositions 1-5 were respectively subjected to experiments according to the preparation method of Example 2, except for the preparation process without the corresponding components, and the rest of the preparation method remained unchanged to obtain the corresponding composition products, which were tested. The test results are shown in Table 1 below, and the dissolution of minoxidil in different compositions is shown below. Figure 1-5 shown.

[0051] Table 1 Comparative test results of different composition components

[0052] The above experimental results show that the product prepared with composition 5 exhibited the best minoxidil dissolution, with no undissolved crystals. Furthermore, no crystals precipitated even after 48 hours of storage, indicating that the solution had reached a relative equilibrium state of dissolution. The components and dissolution states of compositions 1-5 indicate that the addition of menthol effectively enhances the solubility of minoxidil in the solvent, achieving complete dissolution throughout the composition and resolving the problem of poor minoxidil solubility and easy precipitation. The minoxidil content in products prepared using the compositions of the present invention best meets standard requirements and exhibits optimal uniformity.

[0053] Example 5 Comparative experiment of different dissolution methods of minoxidil Minoxidil is a substance that is extremely insoluble in water, so it requires the use of organic solvents for dissolution. Even so, a cosolvent is still needed to increase the solubility of minoxidil to achieve an effective drug concentration. Obtaining a uniform and stable minoxidil solution is a challenge in drug preparation. The following dissolution method was used as a comparative experiment to determine the optimal minoxidil dissolution method. The detailed experimental content is described below. The specific experimental results are shown in Table 2 below.

[0054] Dissolution method 1: Take 3000g of propylene glycol to a liquid preparation tank, then add 1800g of ethanol, add 300g of minoxidil while stirring, stir for 30min, then add 900g of purified water, stir for 20min, to obtain mixture ①, set aside.

[0055] Dissolution method 2: Take 3000g of propylene glycol to a liquid preparation tank, then add 1800g of ethanol, add 300g of minoxidil while stirring, heat to 40°C, stir for 30min, then add 900g of purified water, stir for 20min, to obtain mixture ①, set aside.

[0056] Dissolution method 3: Take 3000 g of propylene glycol to a liquid preparation tank, add 150 g of minoxidil while stirring, stir for 10 minutes, then add 1800 g of ethanol and 150 g of minoxidil in that order, stir for 2 minutes, then add 900 g of purified water, stir for 5 minutes, to obtain mixture ①, set aside.

[0057] Dissolution method 4: Take 3000g of propylene glycol to a liquid preparation tank, add 150g of minoxidil while stirring, stir for 30 minutes, then add 1800g of ethanol and 150g of minoxidil in this order, stir for 10 minutes, then add 900g of purified water, stir for 10 minutes to obtain mixture ①, set aside.

[0058] Dissolution method 5: Take 3000 g of propylene glycol to a liquid preparation tank, add 150 g of minoxidil and 22.0 g of menthol while stirring, stir for 10 minutes, then add 1800 g of ethanol and 150 g of minoxidil in this order, stir for 2 minutes, then add 900 g of purified water, stir for 5 minutes, and obtain mixture ①, which is set aside.

[0059] Table 2 Comparative experimental results of different dissolution methods of minoxidil

[0060] The above experimental results show that the minoxidil dissolved using solution method 5 is the most effective, significantly increasing the minoxidil content and maintaining a uniform and stable content. Although increasing the temperature helps dissolve minoxidil, the dissolution is not complete. However, when menthol and minoxidil are dissolved simultaneously, the minoxidil is completely dissolved, while also saving stirring time and improving dissolution efficiency. The room-temperature dissolution effect of dissolution method 5 is better than the dissolution effect after heating in dissolution method 2, reducing process difficulty while improving industrial production efficiency.

[0061] Experimental Example 6 Comparative experiment on the amount of water added after minoxidil dissolution Because minoxidil is readily soluble in organic solvents, propylene glycol was selected as the solvent. However, to prevent solvent volatilization in the dissolved solution, a certain amount of water was added for neutralization to avoid significant loss of the organic solvent. A water addition screening experiment was conducted. The detailed steps are described below, and the experimental results are shown in Table 3 below.

[0062] Experimental method: Take 3000g of propylene glycol into a liquid preparation tank, add 150g of minoxidil and 22.0g of menthol while stirring, stir for 10 minutes, then add 1800g of ethanol and 150g of minoxidil in sequence, stir for 2 minutes, then add 0g, 400g, 900g, 1400g, and 1900g of purified water respectively, stir for 5 minutes, and obtain a mixture for later use.

[0063] Table 3 Comparative test results of the amount of water added after minoxidil dissolution (n=6)

[0064] The comparative experiments on solvent volatilization in the above experiments show that the organic solvent hardly evaporates when 900ml of water is added, and no minoxidil API precipitates. This effectively controls the uniformity and stability of the minoxidil content, achieving the quality standard of no concentration change over long periods of storage. This achieves the dual effects of ensuring the stability of the product's active ingredients while preventing solvent volatilization, ensuring stable material conditions during industrial production.

[0065] Experimental Example 7 Screening experiment of hinokitiol solvent and dissolution method Hinokitiol is soluble in alkaline aqueous solutions and common organic solvents, but is not easily soluble in water. While it has good solubility in certain organic solvents, complete dissolution remains difficult and time-consuming. Conventional dissolution methods dissolve most of the hinokitiol, but microscopic magnification still leaves some particles undissolved. To address this technical issue, the present invention conducted comparative experiments to screen solvents and dissolution methods for hinokitiol. The specific experimental details are shown below, and the experimental results are shown in Tables 4 and 5.

[0066] 1. Screening of hinokitiol solvents Experimental method: Take 500g of methanol, ethanol, propylene glycol, polyethylene glycol, and butylene glycol respectively into a beaker, add 4g of hinokitiol, stir for 30 minutes, and obtain a mixture for later use.

[0067] 2. Screening of hinokitiol dissolution methods Dissolution method 1: Take 500g of ethanol into a beaker, add 4g of hinokitiol, stir for 30 minutes, and obtain a mixture for later use.

[0068] Dissolution method 2: Take 1000g of ethanol into a beaker, add 4g of hinokitiol, stir for 30 minutes, and obtain a mixture for later use.

[0069] Dissolution method 3: Take 1000 g of ethanol into a beaker, add 4 g of hinokitiol, stir for 20 minutes, and ultrasonicate for 10 minutes to obtain a mixture for later use.

[0070] Dissolution method 4: Take 1000 g of ethanol into a beaker, add 4 g of hinokitiol, stir for 20 minutes, and treat with a reduced pressure ultrasonic device for 10 minutes to obtain a mixture for later use.

[0071] Dissolution method 5: Take 500 g of ethanol and put it into a beaker. Add 4 g of hinokitiol and stir for 20 minutes. Treat with a reduced pressure ultrasonic device for 10 minutes to obtain a mixture for later use.

[0072] Dissolution method 6: Take 200 g of ethanol and put it into a beaker. Add 4 g of hinokitiol and stir for 20 minutes. Treat with a reduced pressure ultrasonic device for 10 minutes to obtain a mixture for later use.

[0073] Dissolution method 7: Take 200 g of ethanol and put it into a beaker. Add 4 g of hinokitiol and stir for 2 minutes. Treat with a reduced pressure ultrasonic device for 10 minutes to obtain a mixture for later use.

[0074] Dissolution method 8: Take 200 g of ethanol and put it into a beaker. Add 4 g of hinokitiol and stir for 2 minutes. Treat with a reduced pressure ultrasonic device for 5 minutes to obtain a mixture for later use.

[0075] Dissolution method 9: Take 150 g of ethanol and put it into a beaker. Add 4 g of hinokitiol and stir for 2 minutes. Treat with a reduced pressure ultrasonic device for 5 minutes to obtain a mixture for later use.

[0076] Table 4 Results of the hinokitiol solvent screening experiment

[0077] Table 5 Screening experiment of hinokitiol dissolution method

[0078] The experimental results show that the above-mentioned cypress phenol is better dissolved in methanol and ethanol. For the safety of the product, non-toxic and harmless ethanol is selected as the solvent. According to the experimental results of the above-mentioned dissolution methods, dissolution methods 4-8 can completely dissolve cypress phenol, but for the convenience of industrial production, dissolution method 8 with less time and less solvent is selected as the best dissolution method. During the dissolution process of cypress phenol, it is treated with a reduced pressure ultrasonic device to dissolve it completely. After being magnified under a microscope, no particles are left, and it will not precipitate after being placed for 48 hours. Compared with the traditional stirring and dissolving method, the use of a reduced pressure ultrasonic device can save a lot of time in this process while reducing the amount of solvent used, providing an advantage for controlling the overall solvent usage of the composition. The good dissolution state of cypress phenol lays a good foundation for the subsequent mixing process steps and reduces the possibility of its precipitation when it encounters water.

[0079] Experimental Example 8 Mixed-method comparative experiment Because raw materials like minoxidil and hinokitiol are insoluble in water, they tend to precipitate out the active ingredients when mixed with water-soluble components, making re-dissolving them extremely difficult. To overcome the mixing difficulties associated with the present composition, the mixing method was optimized. The specific experimental details are shown below, and the experimental data are presented in Table 6 below.

[0080] Experimental content: The composition consists of minoxidil 300g, propylene glycol 3000g, menthol 22.0g, betaine 10g, amino acid complex 10g, glycyrrhetinic acid 7.5g, tocopheryl acetate 5.5g, hinokitiol 4g, pyridoxine 4g, ethanol 2620g, and purified water 1017g; (1) Accurately weigh all the raw materials according to the above formula and set aside; (2) Take 3000g of propylene glycol and put it into the liquid preparation tank. Add 150g of minoxidil and 22.0g of menthol while stirring. Stir for 10 minutes. Then add 1800g of ethanol and 150g of minoxidil in this order. Stir for 2 minutes. Then add 900g of purified water and stir for 5 minutes to obtain mixture ①. Set aside.

[0081] (3) Take 200g of ethanol and put it into a beaker. Add 4g of cypress phenol and stir for 2min. Treat with a reduced pressure ultrasonic device for 5min to obtain mixture ②. Set aside.

[0082] (4) Take 117 g of purified water and put it into the liquid preparation tank. Add 4 g of pyridoxine, 4 g of amino acid complex, and 10 g of betaine while stirring. Stir at 260 rpm for 10 min to obtain mixture ③, which is set aside.

[0083] (5) Take 620 g of ethanol and put it into the liquid preparation tank. Add 5.5 g of tocopherol acetate while stirring. Stir at 150 rpm for 5 min (low speed helps dissolve and avoid material loss). Then add 7.5 g of glycyrrhetinic acid and stir at 300 rpm for 10 min to obtain mixture ④, which is set aside.

[0084] The above mixtures ①-④ are mixed separately according to the following mixing methods to prepare compositions.

[0085] Mixed method 1 Add mixture ③ into the liquid preparation tank, add mixture ② into the liquid preparation tank, mix and stir for 20 minutes to obtain mixture ⑤, set aside.

[0086] Add mixture ① to the liquid preparation tank, turn on the double-screw stirring device, set the speed to 500 rpm, add mixture ④, and control the feeding rate to 10 Hz. Continue stirring for 5 minutes after the addition is completed to obtain mixture ⑥, which is set aside.

[0087] Add mixture ⑤ to the liquid preparation tank, then add mixture ⑥, and stir for 40 minutes at a stirring speed of 300 rpm. After mixing, filter the mixture using a 100-mesh sieve to obtain a composition.

[0088] Hybrid method 2 Add mixture ③ into the liquid preparation tank, add mixture ② into the liquid preparation tank, mix and stir for 20 minutes to obtain mixture ⑤, set aside.

[0089] Add mixture ④ to the liquid preparation tank, turn on the double-screw stirring device, set the speed to 500 rpm, add mixture ①, and control the feeding rate to 10 Hz. Continue stirring for 5 minutes after the addition is completed to obtain mixture ⑥, which is set aside.

[0090] Add mixture ⑤ to the liquid preparation tank, then add mixture ⑥, and stir for 40 minutes at a stirring speed of 300 rpm. After mixing, filter the mixture using a 100-mesh sieve to obtain a composition.

[0091] Mixed Mode 3 Add mixture ② into the liquid preparation tank, add mixture ③ into the liquid preparation tank, mix and stir for 20 minutes to obtain mixture ⑤, set aside.

[0092] Add mixture ④ to the liquid preparation tank, turn on the double-screw stirring device, set the speed to 500 rpm, add mixture ①, and control the feeding rate to 10 Hz. Continue stirring for 5 minutes after the addition is completed to obtain mixture ⑥, which is set aside.

[0093] Add mixture ⑤ to the liquid preparation tank, then add mixture ⑥, and stir for 40 minutes at a stirring speed of 300 rpm. After mixing, filter the mixture using a 100-mesh sieve to obtain a composition.

[0094] Mixing method 4 Add mixture ② into the liquid preparation tank, add mixture ③ into the liquid preparation tank, mix and stir for 20 minutes to obtain mixture ⑤, set aside.

[0095] Add mixture ④ to the liquid preparation tank, turn on the double-screw stirring device, set the speed to 500 rpm, add mixture ①, and control the feeding rate to 10 Hz. Continue stirring for 5 minutes after the addition is completed to obtain mixture ⑥, which is set aside.

[0096] Divide mixture ⑤ and mixture ⑥ into two equal portions. First, add one portion of mixture ⑥ to the preparation tank. Slowly add one portion of mixture ⑤ and stir for 10 minutes. Then, add another portion of mixture ⑥ and stir for 10 minutes. Finally, add the remaining portion of mixture ⑤ to the mixing tank. Stir for a total of 20 minutes at 300 rpm. Filter the mixed materials through a 100-mesh sieve to obtain a composition.

[0097] Mixing method 5 Add mixture ② to the liquid preparation tank, divide mixture ③ into three equal parts, add one part first and stir for 5 minutes, then add the second part and stir for 5 minutes, and finally add the third part and stir for 10 minutes to obtain mixture ⑤, set aside.

[0098] Add mixture ④ to the liquid preparation tank, turn on the double-screw stirring device, set the speed to 500 rpm, add mixture ① by spraying, and control the feeding rate to 10 Hz. Continue stirring for 5 minutes after the addition is completed to obtain mixture ⑥, which is set aside.

[0099] Divide mixture ⑤ and mixture ⑥ into two equal portions. First, add one portion of mixture ⑥ to the preparation tank. Slowly add one portion of mixture ⑤ and stir for 10 minutes. Then, add another portion of mixture ⑥ and stir for 10 minutes. Finally, add the remaining portion of mixture ⑤ to the mixing tank. Stir for a total of 20 minutes at 300 rpm. Filter the mixed materials through a 100-mesh sieve to obtain a composition.

[0100] Table 6. Test results of mixed method comparison experiment

[0101] Conclusion: Based on the above experimental results, different ordering of the components can promote the dissolution of active ingredients such as minoxidil and hinokitiol. Mixing the water-soluble and alcohol-soluble raw materials in batches promotes thorough mixing of the multiple substances and eliminates the risk of precipitation of some raw materials. Furthermore, after adding the minoxidil solution by spraying, no crystals were precipitated after 48 hours, indicating sufficient and stable dissolution. The preparation method of the present composition optimizes product quality from the source of preparation, ensuring that the product does not lose its therapeutic effect due to the precipitation of active ingredients due to long-term storage.

[0102] Experimental Example 9 Stability investigation and comparison experiment To investigate the long-term quality controllability of the composition of the present invention, a comparative experiment was conducted with minoxidil solution, a commonly available product on the market. The products prepared in Experimental Examples 1 and 2, as well as the minoxidil solution, were subjected to a 24-month stability test. Properties were regularly observed and parameters such as content and related substances were tested. The minoxidil solution was manufactured by McNeil Products Ltd. and has a batch number of 3470CP. Detailed test results are shown in Tables 7 and 8 below.

[0103] Table 7 Long-term stability test results of samples prepared in Example 1 and Example 2 Table 8 Long-term stability test results of minoxidil solution

[0104] The long-term stability test results of the above products show that the product prepared in Example 2 is more stable than that of Example 1 and minoxidil solution. After 24 months of storage, no crystals were precipitated, the content remained uniform and stable, and the total amount of related substances was the lowest, with almost no change. The long-term storage quality stability of the composition of the present invention is far superior to that of minoxidil solution. The products prepared by the methods of Examples 1 and 2 showed no change in properties after long-term storage, and the content and related substances were relatively stable. However, after 24 months, the minoxidil solution turned light yellow, and some crystals precipitated, with a maximum particle size of 11 μm. At the same time, the content and related substances all showed significant changes. In summary, the composition of the present invention not only has stable content and related substances over a long period of storage, but also overcomes the problem of minoxidil being easily oxidized after long-term storage.

[0105] Experimental Example 10 Pharmacodynamics trials 1. Experimental Materials 1.1 Experimental animals SPF-grade C57BL / 6 inbred male mice, weighing 20-24 g, were purchased from Beijing Weitonglihua Laboratory Animal Technology Co., Ltd. and housed in an SPF-grade laboratory (temperature 20-26°C, relative humidity 40%-70%) for 3 days with free access to water and food.

[0106] 1.2 Experimental drugs Composition: Sample prepared as in Example 2; Positive control drug: minoxidil liniment, batch number: 20230507, specification: 60mL: 3g, source: Shanxi Zhendong Anxin Biopharmaceutical Co., Ltd. Hinokitiol solution: Prepare by directly dissolving hinokitiol and solvent according to the amount in Example 2.

[0107] 2. Experimental Methods: A mouse model of androgenic alopecia was established by subcutaneous injection of a testosterone propionate suspension at multiple sites. This study used 160 C57BL / 6 male mice, randomly divided into eight groups of 20 mice each: a blank group, a model group, a matrix group, a high-dose hinokitiol group, low-, medium-, and high-dose groups of the present invention's composition, and a positive control group. Topical administration of the drug was applied to the depilated area on the back on the first day of model establishment. Modeling and drug administration continued for 42 consecutive days in each group.

[0108] Gross and trichoscope photographs of the backs of mice in each group were taken on the day of hair removal and on days 7, 14, 21, 28, 35, and 42 of dosing. Hair length was measured with a vernier caliper. Hair growth was observed and scored. The scoring criteria were as follows: no hair growth with flesh-colored or pink skin in the depilated area (0 points); gray skin in the depilated area (1 point); black skin in the depilated area (2 points); black skin in the depilated area with some hair growth (3 points); complete hair coverage with visible flesh color (4 points); and complete hair coverage with no flesh color visible (5 points). Five hairs were collected from the middle of the depilated area per animal weekly. Hair length was measured with a vernier caliper and the average was calculated. The day after the end of day 42 of dosing, mice were sacrificed. A circular skin graft was obtained from the same depilated area on the back of each mouse using a 10 mm punch. All hair was removed with a scalpel, and the hair weight was measured using an analytical balance. Three visual fields were selected under a 100x microscope to count the total number of hair follicles.

[0109] 3. Experimental Animal Grouping and Dosing One hundred and sixty C57BL / 6 male mice were randomly divided according to body weight into eight groups of 20 mice each: blank group, model group, matrix group, high-dose hinokitiol group, low-, medium-, and high-dose combination groups, and a positive control group. Topical administration of the drug to the depilated dorsal area began on day one of model establishment. Half of the animals in each group were modeled and treated continuously for 28 days, and the other half were modeled and treated continuously for 42 days.

[0110] Blank group: 0.02 mL of normal saline was applied to the back of each animal, twice a day, with an interval of 4 hours between each application; Model group: 0.02 mL of normal saline was applied to the back of each animal, twice a day, with an interval of 4 hours between each application; Positive control group: 0.02 mL / animal applied to the back, twice a day, with an interval of 4 hours between each application; Matrix group: 0.02 mL of the test drug matrix was applied to the back of each animal, twice a day, with an interval of 4 hours between each application; Hinokitiol high-dose group: 0.02 mL / animal was applied to the back 3 times a day, with an interval of 4 hours between each application; Low-dose group: 0.02 mL / animal applied to the back, once a day; Medium-dose group: 0.02 mL / animal applied to the back, twice a day, with an interval of 4 hours; High-dose group: Apply 0.02 mL / animal to the back, 3 times a day, with an interval of 4 hours between each application.

[0111] 4. Statistical methods The comparison between experimental data groups was performed using the social science statistical software SPSS17.0 for t-test. express.

[0112] 5. Experimental Results 5.1 Effects on hair growth in androgenic alopecia model mice On the day of hair removal, the backs of mice in all groups showed pink skin, indicating that the hair of mice in each group was in the resting phase, and no obvious vellus hair growth was observed under the hair microscope. On the 7th day of administration, the back skin of half of the mice in the blank group turned gray, the skin of the mice in the model group remained pink, the skin of one mouse in the matrix group turned gray, and the back skin of some mice in the remaining groups turned gray. On the 14th day of administration, obvious hair growth was observed on the backs of the mice in the blank group, and the hair covered most of the hair removal area; hair growth was also observed in all the dosing groups. Except for the high-dose group of the combination, which covered a larger area with hair, only a small area of ​​the other dosing groups was covered with hair, and short hair was visible. Velvet hair was observed under the hair microscope; the back skin of some mice in the model group turned black and a small amount of hair was visible. On the 21st to 28th day of drug administration, the back hair of the mice in the blank group grew rapidly and completely, basically showing a thin layer of coverage. The hair of some animals was thick and smooth, and thick terminal hairs were visible under the hair microscope. The hair of most mice in the other drug-treated groups also grew rapidly, but the hair growth was incomplete. Only a small area of ​​the back of one mouse in the cypress phenol group and the positive drug group was covered with hair. The back of the mice in the other drug-treated groups was covered with hair in most areas, and some mice were even basically covered with hair. The hair of the model group and the matrix group grew slowly, and the hair was rough, dry, and soft, and was not covered with hair. The covered area is larger. On the 35th to 42nd day of administration, the hair of the blank group mice grew fast and thick, shiny and smooth, and the hair was flexible and not easy to break; the hair growth of the model group was slightly better than before, and most areas were covered with hair, but it was relatively fine and soft, and easily fell off when touched. Some animals experienced local hair loss; compared with the cypress phenol group and the positive drug group, the hair of the combination group was shiny, hard and tough. The hair quality of the low-dose, medium-dose and high-dose groups of the combination was significantly better than that of the positive drug group, indicating that the components of the combination have a highly efficient synergistic effect, which not only promotes hair growth, but also makes the new hair thick and not easy to fall off. (See Figure 6 ).

[0113] 5.2 Effect of the composition on hair growth in androgenic alopecia model mice As shown in Table 9 below, prior to administration, hair was not growing and was in a resting phase, with scores of 0. From the 7th to the 42nd day of administration, the hair growth score in the model group was significantly lower than that in the blank group, with a significant difference (P < 0.01). There was no significant difference between the matrix group and the model group (P > 0.05). From the 7th to the 28th day of administration, the hair growth scores of all the treatment groups except the matrix group increased significantly compared with the model group, with a significant difference (P < 0.01). From the 35th to the 42nd day of administration, the difference in hair growth scores between the treatment groups and the model group decreased, with only the medium-dose and high-dose groups of the composition showing significant differences compared with the model group (P < 0.05). Compared with the model group on days 7 and 28 of administration, the hair length of the positive drug group increased significantly, with significant differences (P<0.01). From day 7 to day 42 of administration, the growth score of the high-dose hinokitiol group was higher than that of the model group, indicating that hinokitiol has a hair growth-promoting effect. From day 7 to day 42 of administration, the growth score of the medium-dose and high-dose combination groups was higher than that of the positive drug group. On day 42 of administration, the hair growth score of the positive drug group decreased, indicating drug resistance, while the hair growth score of the combination group continued to grow. This indicates that the drug combination has a sustained effect on promoting hair growth in mice with androgenic alopecia, and the effect is significantly better than that of the positive drug group.

[0114] Table 9 Effect of the composition on hair growth score in androgenic alopecia model mice

[0115]

[0116] 5.3 Effect of the composition on hair length in androgenic alopecia model mice As shown in the results in Table 10 below, from the 14th to the 42nd day of administration, the hair length of the model group was significantly lower than that of the blank group, and the difference was significant (P<0.01). From the 14th to the 28th day of administration, compared with the model group, the hair of each administration group and the positive drug group increased significantly, and the difference was significant (P<0.05). On the 35th day of administration, compared with the model group, the hair length of the low, medium, high groups of the combination and the positive drug group increased significantly, and the difference was significant (P<0.01); from the 14th to the 28th day of administration, the hair length of the administration group increased rapidly, and tended to be flat after the 28th day, indicating that the composition has the effect of promoting hair growth in mice with androgenic alopecia model, and the effect was obvious on the 28th day of administration. After the 28th day of administration, the growth trend of the composition group was more obvious than that of the positive administration group, and no drug resistance was produced, indicating that it has the effect of continuously promoting hair growth (such as Figure 7 shown).

[0117] Table 10 Effects of the composition on hair length in androgenic alopecia model mice (mm) )

[0118] 5.4 Effect of the composition on hair weight in androgenic alopecia model mice Table 11 Figure 8 The results showed that on the 42nd day of administration, the hair weight of the model group was significantly lower than that of the blank group, and the difference was statistically significant (P<0.01). On the 42nd day of administration, the hair weight of the low-dose, medium-dose, and high-dose groups of the composition, as well as the positive drug group, was significantly higher than that of the model group (P<0.05). The hair weight of the low-dose group of the composition was similar to that of the positive drug group, and the medium-dose and high-dose groups of the composition were heavier than that of the positive drug group. This indicates that the composition has the effect of promoting hair growth in mice with androgenic alopecia, and the effect is better than that of the positive control group.

[0119] Table 11 Effects on hair weight of androgenic alopecia model mice ( , n=20)

[0120] 5.5 Effect of the composition on the number of hair follicles in the back skin of androgenic alopecia model mice The results in Table 12 show that at 100x magnification, the model group showed significantly fewer hair follicles compared to the blank group on days 28 and 42 of administration (P < 0.01). There was no significant difference between the matrix group and the model group (P > 0.05). Compared with the model group, the number of hair follicles in the drug-treated group and the positive drug group was significantly higher (P < 0.01). On day 28 of administration, the number of hair follicles in the medium-dose and high-dose groups of the composition was slightly higher than that in the positive drug group. On day 42 of administration, the number of hair follicles in the medium-dose and high-dose groups of the composition remained higher than that in the positive drug group, and the number of hair follicles in the composition group continued to increase, while the number of hair follicles in the positive control group showed a downward trend. These results demonstrate that the composition promotes hair growth in mice with androgenic alopecia, with a steady increase in hair growth. Compared with the positive control group, there was no decrease in hair follicle number due to drug resistance. This demonstrates that the composition has a long-lasting and stable therapeutic effect on hair loss.

[0121] Table 12 Effects of the composition on the number of hair follicles in androgenic alopecia model mice (100×) ( , n=10)

[0122] The results of a 42-day pharmacodynamic study indicate that the composition of the present invention exhibits excellent long-term safety, superior efficacy to the positive control drug, and no acute toxicity. The composition significantly promotes hair growth in mice modeling androgen-induced alopecia, while also increasing hair gloss and flexibility. This not only improves hair appearance (length and density) but also substantially repairs hair follicle structure and increases hair quality. The composition's efficacy in treating alopecia is significantly superior to that of either single component (hinokitiol) or the positive control drug (minoxidil), demonstrating a synergistic mechanism among its components. Furthermore, long-term, high-dose use demonstrates no drug resistance, demonstrating sustained efficacy.

[0123] Experimental Example 11 clinical trials To verify the therapeutic efficacy of the composition of the present invention on patients with alopecia, a trial was conducted using patients clinically diagnosed with this condition. The efficacy of the composition of the present invention on patients with alopecia was evaluated based on the treatment results of real cases. This allowed us to determine whether the composition of the present invention was effective in treating patients with alopecia.

[0124] 1. Case inclusion criteria (1) Patients diagnosed with hair loss; (2) Gender is not limited, age is 20-55 years old; (3) Have not used drugs or cosmetics for treating hair loss within 2 weeks and are in good health without any chronic diseases; (4) Voluntarily participate in this study and sign the informed consent form and cooperate with follow-up.

[0125] 2. Experimental plan 2.1 Case selection According to the above inclusion criteria, 120 patients with alopecia were selected for this study. They were randomly divided into a control group and an experimental group, with 40 patients in each group. Control group 1 consisted of 20 males and 20 females aged 20 to 55 years; control group 2 consisted of 20 males and 20 females aged 25 to 55 years; and the experimental group consisted of 20 males and 20 females aged 22 to 55 years. General information was not statistically significant (P>0.05), indicating comparability among the three groups.

[0126] 2.2 Treatment Methods Test Group: The pharmaceutical composition of the present invention (the product prepared in Example 2 for males and the product prepared in Example 3 for females) was administered in a 1 ml dose, once daily. Control group 1: minoxidil liniment (2% for females and 5% for males), 1 ml / time, once a day; Control group 2: scalp anti-hair loss essence, 3 ml / time, once a day; How to use: Apply the above product evenly to the hair loss area and massage with your hands for 5 minutes to allow it to be fully absorbed; All three groups received treatment for two months, and were followed up 12 weeks after discontinuation of treatment to assess the persistence of efficacy and rebound hair loss rate.

[0127] 3. Evaluation criteria and test results 3.1 Evaluation criteria Cured: New hair grows in the hair loss area with a density similar to that before hair loss. The regenerated hair is not easy to break and the color is consistent with the original hair. The amount of hair loss is reduced, and the amount of hair loss per day is ≤100; Significantly effective: New hair grows in the area of ​​hair loss, which is thinner than before hair loss. The regenerated hair is not easy to break and its color is consistent with the original hair. The amount of hair loss is reduced, and the amount of hair loss per day is ≤200; Effective: New hair grows in the hair loss area, which is sparser than before hair loss. The regenerated hair is easy to break and darker in color than the original hair. The amount of hair loss is reduced, and the amount of hair loss per day is ≤300; Ineffective: No new hair grows in the hair loss area, the density has no significant change compared to before the medication was used, and the daily amount of hair loss remains unchanged or even worsens.

[0128] 3.2 Test results The therapeutic effects, rebound rates and adverse reactions of the three groups of experiments on patients with hair loss are shown in Tables 13, 14 and 15 below.

[0129] Table 13 Comparison of the results of the three groups of patients after 2 months of treatment for hair loss

[0130] Table 14 Comparison of rebound rate among three groups of patients 12 weeks after drug discontinuation

[0131] Table 15 Comparison of adverse reactions among the three groups of patients during treatment

[0132] The above test results indicate that the composition of the present invention has the best therapeutic effect on patients with hair loss, with a therapeutic efficacy rate far exceeding that of minoxidil liniment and scalp anti-hair loss serum, reaching a therapeutic efficacy of 97.5%. The cure rate also reached 82.5%, demonstrating a therapeutic effect far superior to that of control groups 1 and 2. The rebound rate of the three groups of patients 12 weeks after drug discontinuation is shown in Table 14 above. While no rebound occurred in patients using the composition of the present invention, some patients using minoxidil liniment and scalp anti-hair loss serum experienced recurrence of hair loss, with rebound rates of 7.5% and 12.5%, respectively. The persistence of the cure effect was far inferior to that of the composition of the present invention. Furthermore, according to the adverse reactions that occurred during the above-mentioned experiments, none of the 40 patients who used the composition of the present application experienced any adverse reaction symptoms. However, some patients who used minoxidil liniment experienced adverse reactions such as scalp itching or burning, oily or dry scalp flaking, and hair growth in non-target areas. Some patients who used the anti-hair loss serum experienced adverse reactions such as scalp itching or burning, oily or dry scalp flaking, and allergic reactions. The incidence of adverse reactions was as high as 22.5% for minoxidil liniment and 15.0% for the anti-hair loss serum. This demonstrates the safety and reliability of the composition of the present invention.

Claims

1. A hair-raising and hair-protecting series composition for treating hair loss, characterized in that The invention comprises, by weight, 30-800 parts of minoxidil, 300-4000 parts of propylene glycol, 8-50 parts of menthol, 2-30 parts of betaine, 2-30 parts of amino acid complex, 1-25 parts of glycyrrhetinic acid, 1-20 parts of tocopheryl acetate, 0.5-15 parts of hinokitiol, 0.5-15 parts of pyridoxine, 900-5000 parts of ethanol and 200-1800 parts of purified water.

2. A hair-lifting and hair-protecting series composition for treating hair loss according to claim 1, characterized in that The composition consists of 50-500 parts of minoxidil, 1500-3500 parts of propylene glycol, 15-30 parts of menthol, 6-18 parts of betaine, 6-18 parts of amino acid complex, 3-15 parts of glycyrrhetinic acid, 2-12 parts of tocopheryl acetate, 1-8 parts of hinokitiol, 1-8 parts of pyridoxine, 1800-4000 parts of ethanol and 400-1500 parts of purified water in parts by weight.

3. A hair-lifting and hair-protecting series composition for treating hair loss according to claim 1 or 2, characterized in that The composition consists of 250-320 parts of minoxidil, 2700-3200 parts of propylene glycol, 18-25 parts of menthol, 8-14 parts of betaine, 8-14 parts of amino acid complex, 5-10 parts of glycyrrhetinic acid, 4-8 parts of tocopheryl acetate, 2-5 parts of hinokitiol, 2-5 parts of pyridoxine, 2400-3000 parts of ethanol and 800-1200 parts of purified water in parts by weight.

4. A hair-lifting and hair-protecting series composition for treating hair loss according to any one of claims 1 to 3, characterized in that The amino acid complex consists of 10-80 parts of glycine, 2-50 parts of serine, 2-40 parts of glutamic acid, 2-35 parts of aspartic acid, 1-40 parts of leucine, 1-40 parts of alanine, 1-40 parts of lysine, 1-20 parts of arginine, 1-20 parts of tyrosine, 1-20 parts of phenylalanine, 1-20 parts of threonine, 1-20 parts of proline, 1-20 parts of valine, 1-20 parts of isoleucine, 1-20 parts of histidine, 1000-5000 parts of butanediol and 4000-9500 parts of water.

5. A hair-lifting and hair-protecting series composition for treating hair loss according to claim 4, characterized in that The amino acid complex consists of 18-40 parts of glycine, 8-30 parts of serine, 8-20 parts of glutamic acid, 5-15 parts of aspartic acid, 4-15 parts of leucine, 2-10 parts of alanine, 2-10 parts of lysine, 1-10 parts of arginine, 1-10 parts of tyrosine, 1-10 parts of phenylalanine, 1-10 parts of threonine, 1-10 parts of proline, 1-10 parts of valine, 1-10 parts of isoleucine, 1-10 parts of histidine, 2500-3500 parts of butanediol and 6500-8500 parts of water.

6. A hair-lifting and hair-protecting series composition for treating hair loss according to claim 4 or 5, characterized in that The amino acid complex consists of 22-30 parts of glycine, 10-20 parts of serine, 10-15 parts of glutamic acid, 7-10 parts of aspartic acid, 6-10 parts of leucine, 3-6 parts of alanine, 3-6 parts of lysine, 2-5 parts of arginine, 2-5 parts of tyrosine, 2-5 parts of phenylalanine, 2-5 parts of threonine, 2-5 parts of proline, 2-5 parts of valine, 2-4 parts of isoleucine, 1-3 parts of histidine, 2800-3200 parts of butanediol and 6700-8200 parts of water.

7. A method for preparing a hair-raising and hair-protecting series composition for treating hair loss according to any one of claims 1 to 3, characterized in that The preparation method is as follows: (1) Weigh 30-800 parts of minoxidil, 300-4000 parts of propylene glycol, 8-50 parts of menthol, 2-30 parts of betaine, 2-30 parts of amino acid complex, 1-25 parts of glycyrrhetinic acid, 1-20 parts of tocopheryl acetate, 0.5-15 parts of hinokitiol, 0.5-15 parts of pyridoxine, 900-5000 parts of ethanol and 200-1800 parts of purified water according to weight, and set aside; (2) Add 300-4000 parts of propylene glycol to a liquid preparation tank, add 15-400 parts of minoxidil and 8-50 parts of menthol while stirring, stir for 5-20 minutes, then add 500-3800 parts of ethanol and 15-400 parts of minoxidil in this order, stir for 1-10 minutes, then add 150-1500 parts of purified water, stir for 2-15 minutes, and obtain mixture ①, which is set aside; (3) Take 100-300 parts of ethanol and add 0.5-15 parts of hinokitiol to a beaker, stir for 1-10 minutes, and treat with a reduced pressure ultrasonic device for 2-15 minutes to obtain a mixture ②, which is set aside; (4) Take 50-300 parts of purified water to a liquid preparation tank, add 0.5-15 parts of pyridoxine, 2-30 parts of amino acid complex, and 2-30 parts of betaine while stirring, and stir at 260 rpm for 5-30 minutes to obtain mixture ③, which is set aside; (5) Add 300-900 parts of ethanol to a liquid preparation tank, add 1-20 parts of tocopherol acetate while stirring, stir at 150 rpm for 2-15 minutes, then add 1-25 parts of glycyrrhetinic acid, stir at 300 rpm for 5-30 minutes to obtain a mixture ④, which is set aside; (6) Add mixture ② to the liquid preparation tank, divide mixture ③ into three equal parts, add one part first and stir for 2-15 minutes, then add the second part and stir for 2-15 minutes, and finally add the third part and stir for 5-30 minutes to obtain mixture ⑤, which is set aside; (7) Add mixture ④ to the liquid preparation tank, turn on the double-screw stirring device, set the speed to 500 rpm, and add mixture ① by spraying, while controlling the feeding speed to 10 Hz. After the addition is completed, continue stirring for 2-15 minutes to obtain mixture ⑥, which is set aside; (8) Divide mixture ⑤ and mixture ⑥ into two equal parts, first add one part of mixture ⑥ to the liquid preparation tank, slowly add one part of mixture ⑤, stir for 5-30 minutes, then add another part of mixture ⑥, stir for 5-30 minutes, and finally add the remaining part of mixture ⑤ to the mixing tank, stir for 10-50 minutes, and set the stirring speed to 300 rpm; after the total mixing, filter the materials with a 100-mesh sieve to obtain the composite material.

8. The use of a hair-raising and hair-protecting series composition for treating hair loss according to claim 1, characterized in that The composition is used for preparing products for treating hair loss and promoting hair growth.

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