Application of traditional Chinese medicine composition in preparation of medicine for treating alopecia

Abstract

The invention relates to application of a traditional Chinese medicine composition in preparation of a medicine for treating alopecia, which is characterized in that the traditional Chinese medicine composition is prepared from astragalus membranaceus, dried ginger, salted morinda officinalis, cortex dictamni, calcined oyster shell, schisandra chinensis and divaricate saposhnikovia root. The composition can obviously stimulate mouse hair follicle tissue cells to secrete growth factors VEGF and alpha MSH, obviously regulate testosterone and estradiol levels of rats, stimulate release of hepatocyte growth factors and promote hair growth in mouse and rat unhairing areas.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, relates to a new use of a traditional Chinese medicine composition, and particularly relates to the use of a traditional Chinese medicine composition in the preparation of a medicine for hair loss. Background Art

[0002] Androgenic alopecia is an androgen-dependent genetic disease that may have a family history. It is an autosomal dominant, multi-gene disorder. It is also the most common type of hair loss clinically, characterized by a progressive decrease in hair density. The patient's local scalp hair follicles become more sensitive to androgens (primarily dihydrotestosterone), leading to miniaturization of the hair follicles and thinning of the hair shafts. The clinical manifestations are sparse and thinning hair. Androgenic alopecia in men is also known as male pattern baldness, while androgenic alopecia in women is also known as female pattern baldness. Male pattern baldness is mainly seen in men aged 20-30 years old. Hair density begins to decrease on both sides of the forehead, and the hair becomes thin and sparse, gradually extending to the top of the head. The frontal hairline recedes, the forehead becomes higher, and the frontal hairline becomes M-shaped. Hair loss may also begin on the top of the head, or the top and forehead may lose hair simultaneously. Hair loss is progressive, with the forehead and top of the head fading and merging. In severe cases, only the occipital and temporal regions retain hair. The skin in the balding area is smooth, with fine vellus hair visible and no skin atrophy. Increased scalp oil secretion may occur. Female pattern baldness is generally milder, manifesting as gradual thinning of hair on the top of the head, typically sparing the frontal and temporal regions. Hair loss on the top of the head is diffuse, resembling a "Christmas tree" pattern. Hair loss progresses slowly, with severity varying from person to person, but complete baldness on the top of the head is rare. In light of these issues, Traditional Chinese Medicine (TCM) should proactively intervene in the prevention and treatment of hair loss and develop appropriate prescriptions. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to provide a medicine for treating hair loss, which has a significant effect in treating hair loss.

[0004] The technical solutions of the present invention for solving the above problems are as follows:

[0005] A Chinese medicine composition for use in preparing a remedy for hair loss, wherein the use can be any form beneficial for improving the patient's corresponding symptoms, including treatment or prevention. The Chinese medicine composition is made from the following components: 5-15 parts of dried ginger, 15-25 parts of astragalus root, 5-15 parts of salt-cured Morinda officinalis root, 5-15 parts of Dictamni root bark, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis fruit, and 5-15 parts of Saposhnikovia divaricata. The composition of the present invention can be directly ground into a powder or an extract prepared by conventional means in the art. The Chinese medicines used in the composition of the present invention can also be used in the form of directly ground into a powder, an extract, or other processed forms.

[0006] Furthermore, the Chinese medicine composition is made of the following components: 9-11 parts of dried ginger, 19-23 parts of astragalus, 9-11 parts of salt Morinda officinalis, 9-11 parts of Dictamni cortex, 28-34 parts of calcined oyster shell, 6-7 parts of Schisandra chinensis, and 9-11 parts of Saposhnikovia divaricata.

[0007] Furthermore, the Chinese medicine composition is prepared from the following components: 10 parts of dried ginger, 20 parts of astragalus, 10 parts of salt Morinda officinalis, 10 parts of Dictamni cortex, 30 parts of calcined oyster shell, 6 parts of Schisandra chinensis, and 10 parts of Saposhnikovia divaricata.

[0008] Furthermore, the aforementioned hair loss may be androgenic alopecia.

[0009] Furthermore, the preparation method of the aforementioned Chinese medicine composition comprises:

[0010] Take dried ginger, salt Morinda officinalis, Astragalus membranaceus, Dictamni cortex, calcined oyster shell, Schisandra chinensis and Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60℃), spray dry, and obtain dry paste powder.

[0011] Specifically, the drug for androgenic alopecia includes pharmaceutically acceptable excipients or additives.

[0012] Specifically, the pharmaceutically acceptable excipients or additives include fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

[0013] Specifically, the pharmaceutical dosage forms of the drug provided by the present invention include oral dosage forms, injection dosage forms or external dosage forms.

[0014] The dosage forms of the drugs of the present invention are prepared by weighing the raw materials in proportion, adding pharmaceutically acceptable excipients or additives, such as fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases, etc., and preparing according to conventional production methods in the pharmaceutical field to prepare conventional pharmaceutically acceptable dosage forms, including but not limited to decoctions, granules, capsules, tablets, oral liquids, pills, soft capsules, dripping pills, tinctures, syrups, suppositories, gels, sprays, and injections.

[0015] The medicine of the present invention can be prepared by the following method:

[0016] Take 10kg of dried ginger, 10kg of salt Morinda officinalis, 20kg of Astragalus membranaceus, 10kg of Dictamnus cortex, 30kg of calcined oyster shell, 6kg of Schisandra chinensis and 10kg of Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60°C), spray dry to obtain a Chinese medicine composition intermediate, add dextrin, mix well, granulate with 90% ethanol, dry, and granulate to obtain the product.

[0017] The medicine of the present invention is a conventional granule, tablet or capsule.

[0018] The composition of the present invention can significantly improve hair loss in a mouse model of hair loss and significantly increase the levels of α-MSN and VEGF in the mouse skin tissue; in a rat model, it can significantly reduce the testosterone content in serum, increase the estradiol content, and significantly reduce the HGF content in the local skin tissue of the rat, indicating that the traditional Chinese medicine composition can promote hair growth, enhance hair follicle recovery, and promote regional angiogenesis, and has a good therapeutic effect on hair loss. DETAILED DESCRIPTION

[0019] As mentioned above, the present invention aims to provide a use of a Chinese medicine composition in the preparation of a medicament for treating hair loss. A detailed description will be provided below in conjunction with specific experimental details.

[0020] Unless otherwise specified, the following experiments were conducted under conventional conditions or those recommended by the manufacturer. All APIs, excipients, reagents, and instruments used, unless the manufacturer is specified, are commercially available. Unless otherwise specified, all percentages, ratios, proportions, and parts are by weight.

[0021] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention.

[0022] Example 1 Preparation of granules of the composition of the present invention

[0023] Take 10kg of dried ginger, 10kg of salt Morinda officinalis, 20kg of Astragalus membranaceus, 10kg of Dictamnus cortex, 30kg of calcined oyster shell, 6kg of Schisandra chinensis and 10kg of Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60°C), spray dry to obtain a Chinese medicine composition intermediate, add dextrin, mix well, granulate with 90% ethanol, dry, and granulate to obtain the product.

[0024] Example 2 Therapeutic Effects of a Traditional Chinese Medicine Composition on Testosterone-Induced androgenic Alopecia in Mice 1. Experimental Materials

[0025] 1.1 Animals

[0026] Sixty male SPF C57BL / 6J mice, weighing 16–18 g, were purchased from Beijing Sibeifu Biotechnology Co., Ltd. with animal qualification certificate number: 110324231100637441.

[0027] Breeding environment: room temperature 20-26℃, relative humidity controlled at 40-70%, and breeding density of 5 per cage.

[0028] 1.2 Medication

[0029] Chinese medicine composition, intermediate prepared according to the method of Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.; finasteride tablets (Beijing Hanmei Pharmaceutical Co., Ltd., batch number 20210927); testosterone (Roen Reagent Company, batch number 58-22-0); chloral hydrate (Sinopharm Chemical Reagent Co., Ltd., batch number 20200320).

[0030] 1.3 Instruments

[0031] Electronic balance (Sartorius Scientific Instruments, model BS224S); low-temperature centrifuge (Eppendorf, Germany, model 5804R); purified water instrument (Millipore, Germany, model: Milli-Q Plus); animal weighing scale (Shanghai Xiangchuan Electronic Scale Co., Ltd., model: CX-SC-DA); microplate reader (MeiGu Molecular, USA, model: Flexstation3).

[0032] 2. Dosage design

[0033] The daily dosage of the Chinese herbal medicine composition is 96g of crude drug per day. Based on the body surface area conversion method, the equivalent dose for mice is 96g / 60kg*11=17.6g crude drug / kg≈18.0g crude drug / kg. Using a 1 / 4:1 / 2:1 dosing ratio, the low dose is 4.5g crude drug / kg, the medium dose is 9.0g crude drug / kg, and the high dose is 18.0g crude drug / kg. Administration is by oral gavage at 0.2mL / 10g once daily.

[0034] The clinical daily dose of finasteride tablets is 5 mg / day. According to the body surface area conversion method, the equivalent dose for mice is 5 mg / 60*11=0.92 mg / kg≈1 mg / kg.

[0035] 3. Experimental Methods

[0036] C57BL / 6J mice were acclimated for 3 days with free access to feed and water. All mice were anesthetized with 4% chloral hydrate and depilated on either side of the dorsal spine, with a 1 cm × 1 cm area removed. Hair was shaved with a shaver and then depilated with a depilatory cream for 3 minutes. The depilated mice were randomly divided according to body weight into a normal control group, a model control group, a finasteride tablet control group, and high-, medium-, and low-dose groups of the traditional Chinese medicine composition, with 10 mice in each group. Subsequently, 100 μL of 0.2% testosterone solution was evenly applied to the back of mice in all groups except the normal group daily for 12 days. Drug administration began on the first day of depilation. The finasteride tablet group and the traditional Chinese medicine composition group were administered orally at a dose of 0.2 mL / 10 g once daily for 12 consecutive days. The normal and model control groups were given distilled water under the same conditions. On days 8, 10, and 12 after hair removal, 10 hairs were randomly plucked from each mouse and their hair length (mm) was measured with a ruler. The enhancing effect (EE) was calculated as hair length (treatment group) / hair length (model group). On day 12, mice in each group were anesthetized 1 hour after treatment, and skin samples from the depilated area on the back were obtained.

[0037] 4. Statistical methods

[0038] The results were statistically analyzed using t-test.

[0039] 5. Experimental Results

[0040] 5.1 Effects on hair length in the testosterone-induced androgenic alopecia mouse model

[0041] Compared with the normal control group, on days 8 to 10 of treatment, the model group mice had no hair or unmeasurable hair on their backs, while the treated group mice had relatively short hair (3 to 5 mm). By day 12, all groups had grown new hair to varying degrees on their backs. The effect of promoting hair restoration was evaluated by the ratio of hair length (EE) between each treated group and the model group. This suggests that the Chinese herbal composition can promote hair growth in a dose-dependent manner. The results are shown in Table 1.

[0042] Table 1 New hair length of mice in each group on day 8, 10 and 12 ( n=10)

[0043]

[0044] Note: Compared with the model control group, **P<0.01, **P<0.001.

[0045] 5.2 Effects on hair follicle recovery and angiogenic factors in the testosterone-induced androgenic alopecia mouse model

[0046] Compared with the normal control group, after 12 days of treatment, VEGF (vascular endothelial growth factor) and α-MSH levels in the dorsal skin of mice in the model group were significantly reduced, while VEGF and α-MSH levels in the skin of mice in the finasteride group were significantly increased (P < 0.001). The medium and high-dose groups of the Chinese herbal composition also significantly increased these indicators (P < 0.01). This suggests that the Chinese herbal composition can promote angiogenesis in the hair loss area of ​​mice with alopecia and enhance the recovery of hair follicle function. The results are shown in Table 2.

[0047] Table 2 VEGF and α-MSH contents in the skin of the depilated area of ​​mice in each group ( n=10)

[0048]

[0049] Note: Compared with the normal control group, ### P<0.01; compared with the model control group, ***P<0.01, **P<0.01.

[0050] 6. Experimental Conclusion

[0051] The Chinese herbal composition of 18.0 and 9.0 g crude drug / kg can significantly promote hair growth in mice, while significantly increasing VEGF content to promote hair follicle differentiation, and significantly increasing α-MSH content to enhance hair follicle immune privilege, suggesting that the Chinese herbal composition has a certain therapeutic effect on testosterone-induced androgenic alopecia mice.

[0052] Example 3 Therapeutic Effect of the Chinese Medicine Composition on Testosterone Propionate-Induced Rat Androgenic Alopecia Model

[0053] 1. Experimental Materials

[0054] 1.1 Animals

[0055] 60 male SD rats, SPF grade, weighing 160-180 g, were purchased from Sibeifu (Beijing) Biotechnology Co., Ltd., with animal qualification certificate number: No.110324231103712956.

[0056] Rearing environment: Room temperature 20-26°C, relative humidity controlled at 40-70%. Males and females were housed in separate cages, with a stocking density of 5 per cage.

[0057] 1.2 Medication

[0058] The Chinese medicine composition, the intermediate prepared according to the method of Example 1, was provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; finasteride tablets (Beijing Hanmei Pharmaceutical Co., Ltd., batch number 20210927); testosterone propionate (Shanghai Linen Technology Development Co., Ltd., batch number R002673); chloral hydrate (Sinopharm Chemical Reagent Co., Ltd., batch number 20200320); normal saline (Chenxin Pharmaceutical Co., Ltd., batch number: 2101282721).

[0059] 1.3 Instruments

[0060] Electronic balance (Sartorius Scientific Instruments, model BS224S); low-temperature centrifuge (Eppendorf, Germany, model 5804R); purified water instrument (Millipore, Germany, model: Milli-Q Plus); animal weighing scale (Shanghai Xiangchuan Electronic Scale Co., Ltd., model: CX-SC-DA); microplate reader (MeiGu Molecular, USA, model Flexstation3). 2. Dosage design

[0061] 2. Dosage design

[0062] The daily dosage of the Chinese herbal medicine composition is 96g of crude drug per day. Based on the body surface area conversion method, the equivalent dose for rats is 96g / 60kg * 5.6 = 8.98g crude drug / kg, approximately 9.0g crude drug / kg. Using a 1 / 4:1 / 2:1 dosing ratio, the low dose is 2.25g crude drug / kg and the medium dose is 4.5g crude drug / kg. Administration is by oral gavage at 0.1mL / 10g once daily.

[0063] The daily dosage of finasteride tablets is 5 mg / day. According to the body surface area conversion method, the equivalent dose for rats is 5 mg / 60 kg*5.6=0.46 mg / kg≈0.5 mg / kg.

[0064] 3. Experimental Methods

[0065] SD rats were adaptively fed for 3 days with free access to feed and water and randomly divided into a normal control group, a model control group, a finasteride tablet control group, and a high-, medium-, and low-dose group of the Chinese medicine composition, with 10 rats in each group.

[0066] Testosterone propionate was prepared into a solution with a concentration of 5 mg / mL. The normal group of animals was injected subcutaneously with normal saline, and the other groups of animals were injected subcutaneously with multiple points of 5 mg / kg testosterone propionate solution, once a day for 35 consecutive days. The hair loss and sparseness in the observation area of ​​the rat's neck and back indicated that the model was successful. Because the experimental period was long and the local androgen receptors of the animals were reversible, testosterone propionate was required to be continuously injected subcutaneously after the model was successfully established. Thereafter, the injection dose of testosterone propionate was halved. Drug administration began on the first day of modeling. 30 minutes after modeling, the corresponding drugs were administered to the animals in each group by gavage. The normal group and model group were given equal volumes of ultrapure water. The drugs were administered once a day for 35 consecutive days.

[0067] After the final dose, animals were fasted for 12 hours and anesthetized with 10% chloral hydrate. Blood was collected from the abdominal aorta to measure serum testosterone (T) and estradiol (E2) levels. Skin from the alopecia area on the back of the rats was homogenized and centrifuged. The supernatant was collected and assayed for hepatocyte growth factor (HGF) levels.

[0068] 4. Statistical methods

[0069] The results were statistically analyzed using t-test.

[0070] 5. Experimental Results

[0071] 5.1 Effects on serum testosterone and estradiol levels in rats with androgenic alopecia

[0072] Compared with the normal control group, the model rats had significantly increased testosterone levels (P<0.001) and significantly decreased estradiol levels (P<0.01). After drug treatment, the finasteride group had significantly decreased testosterone levels (P<0.001) and significantly increased estradiol levels (P<0.001) compared with the model control group. Compared with the model group, the high-dose group of the Chinese medicine composition showed significant improvement in the above indicators (P<0.01), and the low-dose group also showed significant improvement (P<0.05). The results are shown in Table 3.

[0073] Table 3 Effects of serum testosterone and estradiol levels in rats with androgenic alopecia ( n=10)

[0074]

[0075] Note: Compared with the normal control group, ## P<0.01, ### P<0.001; compared with the model control group, *P<0.05, **P<0.01,

[0076] ***P<0.001.

[0077] 5.2 Effect on Hepatocyte Growth Factor Levels in Skin Tissue of Rats with Androgenic Alopecia Compared with the normal control group, the hepatocyte growth factor (HGF) level in the model rats was significantly decreased (P < 0.01). Compared with the model group, the finasteride tablet group and the high-dose Chinese medicine composition group were significantly increased (P < 0.01), and the medium-dose Chinese medicine composition group was also significantly increased (P < 0.05). The results are shown in Table 4.

[0078] Table 4 Effects on the level of hepatocyte growth factor in skin tissue of rats with androgenic alopecia ( n=10)

[0079]

[0080] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, *P<0.05, **P<0.01.

[0081] 6. Experimental Conclusion

[0082] The Chinese medicine composition can significantly inhibit the testosterone content in the serum of rats with hair loss, increase the estradiol content, and at the same time play a positive regulatory role in HGF, an important factor promoting hair growth in skin tissue, suggesting that the Chinese medicine composition has a certain therapeutic effect on androgenic alopecia in rats induced by testosterone propionate.

[0083] The above embodiments of the present invention are merely examples for the purpose of clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Those skilled in the art will appreciate that other variations or modifications may be made based on the above description. It is not necessary and impossible to enumerate all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the claims of the present invention.

Claims

1. Use of a Chinese medicine composition in preparing a medicament for hair loss, characterized in that: The traditional Chinese medicine composition is prepared from the following components: 5-15 parts of dried ginger, 15-25 parts of astragalus root, 5-15 parts of salt Morinda officinalis, 5-15 parts of Dictamnus dahurica, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis, and 5-15 parts of Saposhnikovia divaricata.

2. The use according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following components by weight: 9-11 parts of dried ginger, 19-23 parts of astragalus, 9-11 parts of salt Morinda officinalis, 9-11 parts of Dictamni cortex, 28-34 parts of calcined oyster shell, 6-7 parts of Schisandra chinensis, and 9-11 parts of Saposhnikovia divaricata.

3. The use according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following components by weight: 10 parts of dried ginger, 20 parts of astragalus, 10 parts of salt Morinda officinalis, 10 parts of Dictamnus dasycarpus, 30 parts of calcined oyster shell, 6 parts of Schisandra chinensis, and 10 parts of Saposhnikovia divaricata.

4. The use according to any one of claims 1 to 3, characterized in that: The preparation method of the Chinese medicine composition comprises: Take dried ginger, salt Morinda officinalis, Astragalus membranaceus, Dictamni cortex, calcined oyster shell, Schisandra chinensis and Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60℃), spray dry, and obtain dry paste powder.

5. The use according to claims 1-3, characterized in that The drug for androgenic alopecia includes pharmaceutically acceptable excipients or additives.

6. The use according to claim 4, characterized in that The pharmaceutically acceptable excipients or additives include fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

7. The use according to any one of claims 1 to 3, characterized in that: The dosage form of the medicine is granules, tablets or capsules.

8. The use according to any one of claims 1 to 3, characterized in that: The preparation method of the medicine comprises: Take 10kg of dried ginger, 10kg of salt Morinda officinalis, 20kg of Astragalus membranaceus, 10kg of Dictamnus cortex, 30kg of calcined oyster shell, 6kg of Schisandra chinensis and 10kg of Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60°C), spray dry to obtain a Chinese medicine composition intermediate, add dextrin, mix well, granulate with 90% ethanol, dry, and granulate to obtain the product.

9. Use of a Chinese medicine composition in the preparation of a medicament for treating or preventing androgenic alopecia, characterized in that: The traditional Chinese medicine composition is prepared from the following components: 5-15 parts of dried ginger, 15-25 parts of astragalus root, 5-15 parts of salt Morinda officinalis, 5-15 parts of Dictamnus dahurica, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis, and 5-15 parts of Saposhnikovia divaricata.

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