Sustained-release medicinal preparation for preventing and treating alopecia as well as preparation method and application thereof

Abstract

The invention provides a sustained-release medicinal preparation for preventing and treating alopecia as well as a preparation method and application of the sustained-release medicinal preparation, and belongs to the technical field of biological medicines. The medicine for preventing and treating alopecia is prepared from the following components: 1 to 2.5 mg of finasteride, 4 to 6 mg of minoxidil, 20 to 60 mg of spirolactone, 10 to 20 mg of isotretinoin, 3 to 8 mg of vitamin B5, 50 to 100 mg of zinc and 5 to 10 mg of vitamin b6. The components cooperate with one another to activate hair follicle stem cells, increase the number of hair follicles and synergistically enhance the ability of promoting hair regeneration, so that a better alopecia prevention and treatment effect is achieved; the pharmaceutical preparation prepared by selecting a specific filler, an adhesive, a sustained-release framework material and a lubricant in a reasonable proportioning range has good sustained-release performance, the dosage and frequency of the medicine are greatly reduced, and the side effect is far lower than that of an oral medicine in a common dosage form.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and in particular relates to a sustained-release drug preparation for preventing and treating hair loss, its preparation method, and its application. Background Technology

[0002] In modern society, hair loss has become a common health and beauty problem affecting a large number of people worldwide, impacting teenagers, adults, and the elderly, and showing a trend towards affecting younger people. Hair loss not only affects an individual's appearance but can also negatively impact mental health, causing feelings of inferiority and anxiety, thus interfering with normal social interactions and daily life. Androgenetic alopecia (also known as seborrheic alopecia) is the most prevalent type, accounting for over 90% of cases. Other types include alopecia areata, postpartum hair loss, and stress-related hair loss. This large patient population has created an urgent market demand for safe and effective hair loss prevention and treatment products.

[0003] Currently, the main methods for preventing and treating hair loss include drug therapy, physical therapy, and hair transplantation surgery. Among these, drug therapy is the preferred option for most patients due to its convenience and relatively low cost. Commonly used clinical medications for preventing and treating hair loss are mainly divided into topical and oral categories. Minoxidil is one of the most widely used topical medications. It promotes hair growth by dilating scalp blood vessels and improving blood supply to hair follicles. However, this drug has drawbacks such as slow onset of action, short half-life, easy relapse after discontinuation, and potential local irritation reactions like scalp itching and redness in some patients. Oral medications, such as finasteride, mainly work by inhibiting 5α-reductase activity and reducing the conversion of testosterone to dihydrotestosterone (DHT). However, it carries certain side effects, potentially causing sexual dysfunction and breast tenderness, and is not suitable for pregnant women and children, limiting its applicability.

[0004] In addition to the aforementioned chemical drugs, there are also a large number of natural hair loss prevention and treatment products on the market that use plant extracts, vitamins, minerals, etc. as their main ingredients. These products usually claim to be highly safe, but most of them lack rigorous clinical trial data to support their claims. The mechanism of action of their active ingredients is unclear, and there are problems such as unstable content of active ingredients and poor effects. As a result, the actual prevention and treatment effects vary, making it difficult to meet patients' needs for efficient and stable treatment.

[0005] The limitations of existing hair loss prevention and treatment drugs in terms of efficacy, safety, and dosage form suitability are becoming increasingly prominent. Developing a new type of hair loss prevention and treatment drug formulation with multi-target mechanism of action, significant efficacy, high safety, good sustained-release effect, and convenient use has become an important research direction in the current pharmaceutical field. It is of great significance for improving the quality of life of hair loss patients and promoting the development of hair loss treatment technology. Summary of the Invention

[0006] In view of this, the purpose of the present invention is to provide a sustained-release drug preparation for preventing and treating hair loss, its preparation method and application.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a drug for preventing and treating hair loss, comprising the following ingredients: 1-2.5 mg finasteride, 4-6 mg minoxidil, 20-60 mg spironolactone, 10-20 mg isotretinoin, 3-8 mg vitamin B5, 50-100 mg zinc, and 5-10 mg vitamin B6.

[0008] The present invention also provides a sustained-release drug formulation for preventing and treating hair loss, comprising the following components: 5-40% of the aforementioned drug for preventing and treating hair loss, 20-45% of sustained-release matrix material, 1-5% of binder, 10-60% of filler, and 0.5-1.5% of lubricant.

[0009] Preferably, the sustained-release matrix material includes one or more of hydroxypropyl methylcellulose and hydroxypropyl cellulose, and the binder includes one or more of povidone K30 and starch paste.

[0010] Preferably, the filler includes one or more of lactose, microcrystalline cellulose, and mannitol.

[0011] Preferably, the lubricant comprises one or more of magnesium stearate and micronized silica gel.

[0012] Preferably, the dosage form of the pharmaceutical preparation includes capsules and tablets.

[0013] The present invention also provides a method for preparing the sustained-release drug formulation, including matrix-type sustained release, membrane-controlled sustained release, reservoir-type sustained release, ion exchange-based sustained release, and gastric retention sustained release. The matrix-type sustained release includes hydrophilic gel matrix type, insoluble matrix type, and erosive matrix type. The membrane-controlled sustained release includes microporous membrane coating and osmotic pump.

[0014] Preferably, it includes the following steps: 1) The hair loss prevention and treatment drug, sustained-release matrix material, and filler are mixed to obtain the material; 2) Mix the adhesive and water to obtain an adhesive solution; 3) The material and the binder solution are mixed to prepare a soft material. The soft material is extruded and spheroidized to obtain granules. The granules are dried, sized, mixed with a lubricant, and compressed into tablets to obtain the sustained-release drug formulation.

[0015] Preferably, in step 1), the mixing speed is 100~500 rpm and the mixing time is 10~20 min; Step 2) The concentration of the adhesive solution is 5-15%; Step 3) The conditions for the extrusion rounding method are set as follows: the thickness of the extrusion plate is 0.5mm~2.0mm, the extrusion speed is 10rpm~50rpm, the rounding speed is 300rpm~600rpm, and the rounding time is 5min~15min; The drying process is carried out until the particle moisture content is 2-3%. The parameters during drying are set as follows: inlet air temperature 50-60℃, fan speed 800-1200rpm, material temperature 30-40℃, and air volume 10-30m³. 3 / min.

[0016] The present invention also provides the application of the described drug, the described sustained-release drug formulation, or the sustained-release drug formulation prepared by the described preparation method in the preparation of drugs for preventing and treating hair loss.

[0017] Compared with the prior art, the present invention has the following beneficial effects: The present invention contains finasteride, minoxidil, spironolactone, isotretinoin, vitamin B5, zinc, and vitamin B6. These components work together to activate hair follicle stem cells, increase the number of hair follicles, and synergistically enhance the ability to promote hair regeneration, thereby achieving better hair loss prevention and treatment effects, improving drug efficacy and safety, and can be used for clinical treatment, adjuvant treatment, and related treatments to prevent recurrence of hair loss.

[0018] The present invention selects specific fillers, binders, sustained-release matrix materials and lubricants, and prepares drug formulations with good sustained-release performance within a reasonable ratio range, which greatly reduces the dosage and frequency of drug administration, and the side effects are far lower than those of ordinary oral drugs. Detailed Implementation

[0019] This invention provides a drug for preventing and treating hair loss, comprising the following ingredients: 1-2.5 mg finasteride, 4-6 mg minoxidil, 20-60 mg spironolactone, 10-20 mg isotretinoin, 3-8 mg vitamin B5, 50-100 mg zinc, and 5-10 mg vitamin B6.

[0020] In this invention, the preferred dosage of finasteride is 1.5-2 mg. Finasteride, as a "5α-reductase inhibitor," can inhibit the conversion of testosterone in the body into the more potent "dihydrotestosterone (DHT)." DHT is a core factor leading to androgenetic alopecia, shortening the hair follicle growth phase and causing hair follicles to shrink. The preferred dosage of minoxidil is 5 mg. Minoxidil improves blood supply to hair follicles by dilating scalp capillaries, providing more nutrients to the hair follicles; it also activates hair follicles in the "resting phase," prolonging the "growth phase" and reducing hair loss. The preferred dosage of spironolactone is 35-55 mg, further... The preferred dosage is 50 mg. Spironolactone has both "anti-androgen" and "potassium-sparing diuretic" effects, competitively inhibiting the binding of androgens to hair follicle receptors, reducing DHT damage to hair follicles, reducing minoxidil-induced edema, and mildly inhibiting testosterone synthesis. The preferred dosage of isotretinoin is 10 mg. Isotretinoin can regulate the keratinization process of hair follicle epithelial cells, inhibit excessive proliferation and keratinization of epithelial cells, help unclog blocked hair follicle openings, restore normal hair growth channels, thus allowing hair to grow normally. It can significantly inhibit sebaceous gland activity, reduce sebum secretion, thereby reducing sebum stimulation of hair follicles and creating a relatively warm environment for hair follicles. The growth environment of the hair follicles may have a certain auxiliary effect in improving seborrhea-type androgenetic alopecia. It has a certain anti-inflammatory effect, which can inhibit the inflammatory response around the hair follicles, reduce the damage of inflammation to the hair follicles, and thus help protect hair follicle function and prevent further aggravation of hair loss. The preferred dosage of vitamin B5 is 5mg. Vitamin B5 improves the scalp microenvironment (such as relieving dryness and inflammation) by supplementing the nutrients needed by the scalp and hair, enhancing hair resilience, and reducing the appearance of hair loss caused by "fragile hair and breakage." The preferred dosage of zinc is 50mg. Zinc is a key catalyst for hair follicle cell division and proliferation, and the activation of hair follicle stem cells... Zinc is essential for maintaining the function of dermal papilla cells, participating in DNA synthesis and cell metabolism. It also participates in cysteine ​​metabolism, promoting keratin cross-linking to form a stable hair structure. Zinc can inhibit excessive activity of sebaceous gland cells, reduce sebum secretion, and prevent excessive oil from clogging hair follicles or stimulating follicle miniaturization. Zinc has anti-inflammatory properties, inhibiting local inflammatory factors on the scalp, reducing inflammation around hair follicles, and protecting them from damage. Zinc is also an important element for maintaining the balance of the immune system, regulating the function of immune cells such as T lymphocytes and macrophages, preventing excessive activation of the immune response, and reducing the effect of finasteride on libido.The preferred dosage of vitamin B6 is 8 mg. Vitamin B6 promotes the decomposition, transformation, and utilization of amino acids (such as cysteine ​​and methionine, core components of keratin), helps hair follicle cells synthesize sufficient and structurally normal keratin, participates in the metabolic regulation of sebaceous glands, inhibits excessive activity of sebaceous gland cells, reduces sebum secretion, avoids excessive oil clogging hair follicle openings and stimulating hair follicle miniaturization, helps regulate neurotransmitter levels, alleviates the negative impact of stress on hair follicles, reduces the proportion of telogen effluvium, and helps maintain hormone metabolic balance. It has a slight auxiliary effect in improving hair loss aggravated by hormone metabolic disorders in androgenetic alopecia. It also regulates the activity of immune cells (such as lymphocytes and macrophages), enhances the body's ability to regulate inflammation, reduces inflammatory responses around hair follicles, and prevents inflammatory damage to hair follicles.

[0021] The present invention also provides a sustained-release drug formulation for preventing and treating hair loss, comprising the following components: 5-40% of the aforementioned drug for preventing and treating hair loss, 20-45% of sustained-release matrix material, 1-5% of binder, 10-60% of filler, and 0.5-1.5% of lubricant.

[0022] In this invention, the dosage of the hair loss prevention and treatment drug is preferably 10-30%; the sustained-release matrix material includes one or more of hydroxypropyl methylcellulose and hydroxypropyl cellulose, and the dosage of the sustained-release matrix material is preferably 25-40%; the binder includes one or more of povidone K30 and starch paste, and the dosage of the binder is preferably 2-4%; the filler includes one or more of lactose, microcrystalline cellulose and mannitol, and the dosage of the filler is preferably 20-50%; the lubricant includes one or more of magnesium stearate and micronized silica gel, and the dosage of the lubricant is preferably 0.8-1.2%; the dosage form of the drug preparation includes capsules and tablets.

[0023] The present invention also provides a method for preparing the aforementioned pharmaceutical formulation, including matrix-based sustained release, membrane-controlled sustained release, reservoir-based sustained release, sustained release based on ion exchange technology, and gastric retention sustained release. The matrix-based sustained release includes hydrophilic gel matrix type, insoluble matrix type, and erosive matrix type. The membrane-controlled sustained release includes microporous membrane coating and osmotic pump.

[0024] The present invention specifically includes the following steps: 1) The hair loss prevention and treatment drug, sustained-release matrix material, and filler are mixed to obtain the material; 2) Mix the adhesive and water to obtain an adhesive solution; 3) The material and the binder solution are mixed to prepare a soft material. The soft material is extruded and spheroidized to obtain granules. The granules are dried, sized, mixed with a lubricant, and compressed into tablets to obtain the sustained-release drug formulation.

[0025] In this invention, the aforementioned hair loss prevention and treatment drug, sustained-release matrix material, and filler are mixed to obtain a material. The mixing speed is preferably 100-500 rpm, more preferably 200-400 rpm, and even more preferably 300 rpm; the mixing time is preferably 10-20 min, more preferably 12-18 min, and even more preferably 15 min.

[0026] In this invention, an adhesive and water are mixed to obtain an adhesive solution. The concentration of the adhesive solution is preferably 5-15%, more preferably 8-12%, and even more preferably 10%.

[0027] In this invention, a soft material is prepared by mixing the material and the adhesive solution, and the soft material is extruded and spheroidized to obtain granules. The granules are dried, sized, mixed with a lubricant, and tableted to obtain the pharmaceutical preparation. The conditions for the extrusion rounding method are set as follows: the thickness of the extrusion orifice plate is preferably 0.5mm~2.0mm, more preferably 0.8~1.8mm, and even more preferably 1.5mm; the extrusion speed is preferably 10rpm~50rpm, more preferably 20~40rpm, and even more preferably 30rpm; the rounding speed is preferably 300rpm~600rpm, more preferably 400rpm~500rpm; the rounding time is preferably 5min~15min, more preferably 8~12min, and even more preferably 10min; the drying process is carried out until the moisture content of the particles is 2~3%, and the parameters during drying are set as follows: the inlet air temperature is preferably 50~60℃, more preferably 52~58℃, and even more preferably 55℃; the blower speed is preferably 800~1200rpm, more preferably 900~1100rpm, and even more preferably 1000rpm; the material temperature is preferably 30~40℃, more preferably 32~38℃, and even more preferably 35℃; the air volume is preferably 10~30m³ / min. 3 / min, further preferably 15~25m 3 / min, more preferably 20m 3 / min.

[0028] The present invention also provides the application of the described drug, the described sustained-release drug formulation, or the sustained-release drug formulation prepared by the described preparation method in the preparation of drugs for preventing and treating hair loss.

[0029] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0030] Example 1

[0031] A medication for preventing and treating hair loss consists of the following ingredients: 2mg finasteride, 5mg minoxidil, 50mg spironolactone, 10mg isotretinoin, 5mg vitamin B5, 50mg zinc, and 8mg vitamin B6.

[0032] Example 2

[0033] A medication for preventing and treating hair loss consists of the following ingredients: 1 mg finasteride, 4 mg minoxidil, 20 mg spironolactone, 15 mg isotretinoin, 3 mg vitamin B5, 80 mg zinc, and 5 mg vitamin B6.

[0034] Example 3

[0035] A medication for preventing and treating hair loss consists of the following ingredients: 2.5 mg finasteride, 6 mg minoxidil, 60 mg spironolactone, 20 mg isotretinoin, 8 mg vitamin B5, 100 mg zinc, and 10 mg vitamin B6.

[0036] Example 4

[0037] A sustained-release drug formulation for preventing and treating hair loss comprises the following components: 20% of the hair loss prevention and treatment drug of Example 1, 30% hydroxypropyl methylcellulose, 3% povidone K30, 20% lactose, 26% microcrystalline cellulose, and 1% micronized silica.

[0038] The preparation method of the sustained-release drug formulation is as follows: 1) Crush the hair loss prevention and treatment drugs, hydroxypropyl methylcellulose, lactose and microcrystalline cellulose separately, pass them through a 90-mesh sieve to ensure that the powder is uniform, and then put them into a mixer to mix the materials. The mixing speed is 300 rpm and the mixing time is 15 minutes. 2) Mix povidone K30 and water to obtain a 10% povidone K30 solution; 3) A soft material is prepared by mixing the material with a povidone K30 solution. The soft material is then extruded and spheroidized to obtain granules. The conditions for the extrusion and spheroidization method are set as follows: extrusion plate thickness is 1 mm, extrusion speed is 30 rpm, spheroidization speed is 500 rpm, and spheroidization time is 10 min. The granules are then dried until the moisture content is 3%. The drying parameters are set as follows: inlet air temperature is 55℃, fan speed is 1000 rpm, material temperature is 35℃, and air volume is 20 m³ / min. 3 After granulation by passing the granules through an 18-mesh sieve, the granules are mixed with micronized silica gel in a mixer at 15 rpm for 10 min. The mixed granules are then placed into a tablet press for tableting to obtain the sustained-release drug formulation.

[0039] Example 5

[0040] A sustained-release drug formulation for preventing and treating hair loss comprises the following components: 5% of the hair loss prevention and treatment drug of Example 1, 45% hydroxypropyl methylcellulose, 1% povidone K30, 10% lactose, 38.5% microcrystalline cellulose, and 0.5% micronized silica.

[0041] The preparation method of the sustained-release drug formulation is as follows: 1) Crush the hair loss prevention and treatment drugs, hydroxypropyl methylcellulose, lactose and microcrystalline cellulose separately, pass them through an 80-mesh sieve to ensure that the powder is uniform, and then put them into a mixer to mix the materials. The mixing speed is 100 rpm and the mixing time is 10 min. 2) Mix povidone K30 and water to obtain a 5% povidone K30 solution; 3) A soft material is prepared by mixing the material with a povidone K30 solution. The soft material is then extruded and spheroidized to obtain granules. The conditions for the extrusion and spheroidization method are set as follows: extrusion plate thickness is 0.5 mm, extrusion speed is 10 rpm, spheroidization speed is 300 rpm, and spheroidization time is 5 min. The granules are then dried until the moisture content is 2%. The drying parameters are set as follows: inlet air temperature is 50℃, fan speed is 800 rpm, material temperature is 30℃, and air volume is 10 m³ / min. 3 After granulation by passing the granules through a 15-mesh sieve, the granules are mixed with micronized silica gel in a mixer at 10 rpm for 5 minutes. The mixed granules are then placed into a tablet press for tableting to obtain the sustained-release drug formulation.

[0042] Example 6

[0043] A sustained-release drug formulation for preventing and treating hair loss comprises the following components: 40% of the hair loss prevention and treatment drug of Example 1, 20% hydroxypropyl methylcellulose, 5% povidone K30, 13.5% lactose, 20% microcrystalline cellulose, and 1.5% micronized silica.

[0044] The preparation method of the sustained-release drug formulation is as follows: 1) Crush the hair loss prevention and treatment drugs, hydroxypropyl methylcellulose, lactose and microcrystalline cellulose separately, pass them through a 100-mesh sieve to ensure that the powder is uniform, and then put them into a mixer to mix the materials. The mixing speed is 500 rpm and the mixing time is 20 minutes. 2) Mix povidone K30 and water to obtain a 15% povidone K30 solution; 3) A soft material is prepared by mixing the material with a povidone K30 solution. The soft material is then extruded and spheroidized to obtain granules. The conditions for the extrusion and spheroidization method are set as follows: extrusion plate thickness is 2.0 mm, extrusion speed is 50 rpm, spheroidization speed is 600 rpm, and spheroidization time is 15 min. The granules are then dried until the moisture content is 3%. The drying parameters are set as follows: inlet air temperature is 60℃, fan speed is 1200 rpm, material temperature is 40℃, and air volume is 30 m³ / min. 3 After granulation by passing the granules through a 20-mesh sieve, the granules are mixed with micronized silica gel in a mixer at a speed of 20 rpm for 15 min. The mixed granules are then placed into a tablet press for tableting to obtain the sustained-release drug formulation.

[0045] Experimental Example 1

[0046] Two hundred and eighty patients with androgenetic alopecia were selected and randomly divided into experimental groups 1-13 and a control group, with 20 patients in each group. The grouping is as follows: Blank control group: No treatment was given; Experimental group 1: Oral administration of 2mg finasteride once daily; Experimental group 2: Oral administration of 5mg minoxidil once daily; Experimental group 3: Oral administration of 10mg isotretinoin once daily; Experimental group 4: Oral administration of 50 mg spironolactone once daily; Experimental group 5: Oral administration of 5mg vitamin B5, once daily; Experimental group 6: Oral administration of 50mg zinc once daily; Experimental group 7: Oral administration of 8mg vitamin B6, once daily; Experimental group 8: Oral administration of 2mg finasteride + 5mg minoxidil + 10mg isotretinoin + 50mg spironolactone + 5mg vitamin B5 + 50mg zinc + 8mg vitamin B6 (the drugs in Example 1), once daily; Experimental group 9: The drug of Example 2, once daily; Experimental group 10: The drug of Example 3, once daily; Experimental group 11: Orally administer the sustained-release drug formulation prepared in Example 4 once daily; Experimental group 12: Orally administered the sustained-release drug formulation prepared in Example 5 once daily; Experimental group 13: Orally administer the sustained-release drug formulation prepared in Example 6 once daily; Before treatment and 5 months after treatment, unpolarized light source photographs of the fixed target areas on the left, right, and top of the head of the patients were taken using a trichoscopy instrument at 70x magnification, and the number of hairs per square centimeter was calculated.

[0047] Experimental results are shown in Table 1.

[0048] Table 1. Number of hairs per square centimeter in patients from different treatment groups ( ±s)

[0049] As shown in Table 1, the number of hairs per square centimeter in the experimental groups was higher than that in the control group (no treatment). All the drugs in experimental groups 1-13 of this invention were effective. Among them, experimental groups 11-13 with sustained-release technology showed significantly better results in increasing hair count than experimental groups 8-10 without sustained-release technology. Conversely, experimental groups 8-10 without sustained-release technology showed significantly better results in increasing hair count than the groups using finasteride alone, minoxidil alone, isotretinoin alone, spironolactone alone, vitamin B5 alone, zinc alone, and vitamin B6 alone. Therefore, the specific proportions of finasteride, minoxidil, isotretinoin, spironolactone, zinc, and vitamins B5 and B6 in this invention have a synergistic effect. Furthermore, the addition of sustained-release technology prolongs the effective time, significantly promotes hair regeneration, and achieves better results in preventing and treating hair loss.

[0050] Experimental Example 2

[0051] Sixty patients with androgenetic alopecia were selected and randomly divided into experimental groups A through C, with 20 patients in each group. The grouping is as follows: Experimental group A: Oral administration of 2mg finasteride + 5mg minoxidil + 10mg isotretinoin + 5mg vitamin B5 + 50mg zinc + 8mg vitamin B6, once daily; Experimental group B: Oral administration of 2mg finasteride + 5mg minoxidil + 10mg isotretinoin + 50mg spironolactone + 5mg vitamin B5 + 50mg zinc + 8mg vitamin B6 (the drugs in Example 1), once daily; Experimental group C: Orally administer the sustained-release drug formulation prepared in Example 4 once daily.

[0052] The side effects of medication were statistically analyzed in patients A through C of the experimental group.

[0053] Experimental results are shown in Table 2.

[0054] Table 2. Statistics of Patient Side Effects

[0055] As shown in Table 2, the frequency of edema in experimental group A was significantly higher than that in experimental group B. This is directly related to the addition of spironolactone to experimental group A, indicating that spironolactone has a good effect on reducing edema induced by minoxidil. In the comparison between experimental group B and experimental group C, it can be found that all kinds of side effects in experimental group C were significantly reduced. This also proves the applicability of the sustained-release process. In particular, the addition of the sustained-release process represents a substantial breakthrough in reducing side effects, especially for the characteristic of androgenetic alopecia treatment that requires lifelong medication. This is a technical solution that has never been adopted in the field of hair care drugs.

[0056] Experimental Example 3

[0057] Sustained-release performance tests of the sustained-release drug formulations prepared in Examples 4-6

[0058] Using commercially available finasteride and minoxidil, as well as the sustained-release drug formulations in Examples 4-6, as the main indicators, dissolution curves were determined based on the saturated solubility results of the active pharmaceutical ingredients. The specific dissolution curve methods are shown in Table 3.

[0059] Table 3. Methods for determining dissolution curves

[0060] Experimental results are shown in Table 4.

[0061] Table 4 Dissolution curve test results

[0062] As shown in Table 4, compared with the currently commercially available hair growth drugs finasteride and minoxidil, the drug formulation of the present invention has a small difference in dissolution between finasteride and minoxidil, and the release time can cover 24 hours, which meets the requirements. The cumulative dissolution rate of finasteride in 24 hours is about 80%, and the cumulative dissolution rate of minoxidil in 24 hours is about 99%, and the drugs are completely released, exhibiting good sustained-release performance.

[0063] As can be seen from the above embodiments and experimental examples, the synergistic effects of the components of this invention—finasteride, minoxidil, spironolactone, isotretinoin, vitamin B5, zinc, and vitamin B6—can activate hair follicle stem cells, increase the number of hair follicles, and synergistically enhance the ability to promote hair regeneration, thus achieving better hair loss prevention and treatment effects. The drug formulation prepared by selecting specific fillers, adhesives, sustained-release matrix materials, and lubricants within a reasonable ratio range exhibits excellent sustained-release performance, significantly reducing the dosage and frequency of drug administration, and resulting in far fewer side effects than ordinary oral medications.

[0064] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A drug for preventing and treating hair loss, characterized in that, The composition comprises 1-2.5 mg finasteride, 4-6 mg minoxidil, 20-60 mg spironolactone, 10-20 mg isotretinoin, 3-8 mg vitamin B5, 50-100 mg zinc, and 5-10 mg vitamin B6.

2. A sustained release pharmaceutical preparation for preventing and treating hair loss, characterized by comprising, The composition comprises 5-40% of the hair loss preventing drug of claim 1, 20-45% of the sustained release matrix material, 1-5% of the binder, 10-60% of the filler, and 0.5-1.5% of the lubricant.

3. The sustained release pharmaceutical preparation according to claim 2, characterized in that, The sustained release matrix material comprises one or more of hypromellose and hydroxypropyl cellulose, and the binder comprises one or more of povidone K30 and starch paste.

4. The sustained release pharmaceutical preparation according to claim 2, characterized in that, The filler comprises one or more of lactose, microcrystalline cellulose, and mannitol.

5. The sustained release pharmaceutical formulation according to claim 2, wherein The lubricant comprises one or more of magnesium stearate and colloidal silicon dioxide.

6. The sustained release pharmaceutical formulation according to claim 2, wherein The dosage form of the pharmaceutical preparation comprises capsules and tablets.

7. A process for the preparation of a sustained release pharmaceutical formulation according to any one of claims 2 to 6, characterised in that, The sustained release includes matrix sustained release, membrane controlled sustained release, reservoir sustained release, ion exchange technology based sustained release, and gastric retention sustained release, wherein the matrix sustained release includes hydrophilic gel matrix, insoluble matrix, and dissolvable matrix, and the membrane controlled sustained release includes microporous membrane coating and osmotic pump.

8. The preparation method according to claim 7, characterized in that, The method specifically comprises the following steps: 1) mixing the hair loss preventing drug of claim 1, the sustained release matrix material, and the filler to obtain a mixture; 2) mixing the binder and water to obtain a binder solution; 3) mixing the mixture and the binder solution to obtain a soft material, and then preparing granules by extrusion and spheronization, drying and sizing the granules, mixing the granules with the lubricant, and compressing the mixture to obtain the sustained release pharmaceutical preparation.

9. The preparation method according to claim 8, characterized in that, In step 1), the rotation speed of the mixing is 100-500 rpm, and the mixing time is 10-20 min. In step 2), the concentration of the binder solution is 5-15%. In step 3), the extrusion and spheronization are performed under the following conditions: the thickness of the extrusion orifice plate is 0.5-2.0 mm, the extrusion speed is 10-50 rpm, the spheronization rotation speed is 300-600 rpm, and the spheronization time is 5-15 min. The drying is to the granule moisture content 2~3%, the parameter setting when the drying is: the inlet air temperature 50~60℃, the fan speed 800~1200rpm, the material temperature 30~40℃, the air volume 10~30m 3 / min.

10. Use of the hair loss preventing drug of claim 1, the sustained release pharmaceutical preparation of any one of claims 2-6, or the sustained release pharmaceutical preparation prepared by the preparation method of claims 7-9 in the preparation of a hair loss preventing drug.

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