Pharmaceutical formulation for treating breast hyperplasia and preparation method therefor

Abstract

A pharmaceutical formulation for treating breast hyperplasia and a preparation method therefor. The pharmaceutical formulation comprises a drug-loaded microneedle layer, a backing layer connected to the drug-loaded microneedle layer, and a medical blank adhesive patch adhered to the backing layer. The drug-loaded microneedle layer is prepared from the following raw materials: a traditional Chinese medicine compound clear paste, a microneedle matrix and purified water. The traditional Chinese medicine compound clear paste is prepared from the following raw materials: radix bupleuri chinensis, curcumae radix, rhizoma cyperi, radix paeoniae alba, frankincense, rhizoma pinelliae, bulbus fritillariae thunbergii, spica prunellae, camphor essential oil, turpentine and a 70% ethanol solution. The backing layer is prepared from the following raw materials: a backing layer matrix and purified water.

Description

A pharmaceutical preparation for treating breast hyperplasia and its preparation method Technical Field This invention belongs to the field of pharmaceutical technology, specifically relating to a pharmaceutical preparation for treating breast hyperplasia and its preparation method. Background Technology Breast hyperplasia is a common breast disease characterized by the abnormal proliferation of non-cancerous cells in breast tissue, which may lead to symptoms such as breast swelling, pain, and breast lumps, and in severe cases, carries the risk of malignant transformation. In recent years, the incidence of this disease has been increasing year by year. Existing treatment methods include drug therapy, surgical removal, and physical therapy, but all have certain limitations and side effects. Drug therapy can relieve symptoms, but long-term use may lead to liver and kidney damage; surgical treatment, while effectively removing diseased tissue, is highly invasive and has a long recovery period. Therefore, finding an efficient, safe, and non-invasive treatment method is a key focus of current research. With the development of modern drug delivery technology, traditional Chinese medicine microneedle patches have emerged as a novel topical drug formulation. These patches utilize microneedles to penetrate the stratum corneum of the skin, directly delivering the drug components to the subcutaneous tissue. This avoids the reduced efficacy of traditional oral and topical medications due to poor gastrointestinal absorption or skin barrier effects. The characteristics of traditional Chinese medicine microneedle patches lie in their ability to improve drug bioavailability, reduce systemic adverse reactions, and demonstrate good patient compliance and promising application prospects. However, there is currently limited research and application of traditional Chinese medicine microneedle patches for treating breast hyperplasia, and existing technologies urgently need further optimization and innovation. Summary of the Invention

[0005] To address the above issues, this invention provides a pharmaceutical preparation for treating breast hyperplasia and its preparation method. The dosage form is a traditional Chinese medicine compound microneedle patch. The active ingredient is a compound ointment prepared from raw herbs such as Bupleurum chinense, Curcuma longa, Cyperus rotundus, Paeonia lactiflora, Boswellia carterii, Pinellia ternata, Fritillaria thunbergii, and Prunella vulgaris. A PDMS (polydimethylsiloxane) microneedle negative mold is used as the pharmaceutical preparation mold. A soluble drug-loaded microneedle layer is prepared using a composite gel material, and a microneedle backing layer is prepared using a polymer with certain flexibility and tensile strength. The prepared microneedles have high strength and are not prone to collapse, and have strong skin puncture ability. Under the synergistic effect of multiple components, an effective combination of improved drug transdermal rate and skin repair and regeneration can be achieved, thereby enhancing the therapeutic effect. To achieve the above objectives, the technical solution adopted by the present invention is as follows: The present invention provides a pharmaceutical preparation for treating breast hyperplasia, the pharmaceutical preparation comprising a drug-loaded microneedle layer, a backing layer in contact with the drug-loaded microneedle layer, and a medical blank adhesive tape for adhering to the backing layer. Furthermore, the drug-loaded microneedle layer is prepared from the following raw materials: traditional Chinese medicine compound extract, microneedle matrix, and purified water. Furthermore, the traditional Chinese medicine compound ointment is prepared from the following raw materials: Bupleurum chinense, Curcuma longa, Cyperus rotundus, Paeonia lactiflora, Boswellia carterii, Pinellia ternata, Fritillaria thunbergii, Prunella vulgaris, camphor oil, turpentine oil, and 70% (v / v) ethanol solution. The weight ratio of Bupleurum chinense, Curcuma longa, Cyperus rotundus, Paeonia lactiflora, Boswellia carterii, Pinellia ternata, Fritillaria thunbergii, Prunella vulgaris, camphor oil, and turpentine oil is 3:2:1.5:1:1:0.5:0.5:0.5:1:1. Furthermore, the microneedle matrix is ​​selected from one or more of CMC-Na (sodium carboxymethyl cellulose), CS (chondroitin sulfate), silk fibroin, PVP K90 (polyvinylpyrrolidone K90), and Gantrez AN-139 (methyl vinyl ether-maleic anhydride copolymer AN-139). Furthermore, the backing layer is prepared from the following raw materials: backing layer matrix and purified water, wherein the backing layer matrix is ​​selected from one of HA (hyaluronic acid), HPMC (hydroxypropyl methylcellulose) and PVA (polyvinyl alcohol). Preferably, the backing matrix is ​​HA, and the molecular weight of HA is 10-300 kDa. Furthermore, the pharmaceutical preparation is prepared by casting using a PDMS microneedle negative mold. The parameters of the PDMS microneedle negative mold are as follows: the needle shape is conical, the needle height is 600 μm, the diameter of the bottom surface of the cone is 300 μm, the needle tip diameter is 15-20 μm, the array number is 40×40, the overall size is 25 mm×25 mm, and the overall groove depth is 1.5 mm. Furthermore, the weight ratio of the traditional Chinese medicine compound extract, the microneedle matrix, and the backing matrix is ​​1:0.4-1.5:0.2-0.6. The preparation method of the traditional Chinese medicine compound extract includes the following steps: Step A1: Weigh out the following ingredients in a weight ratio of 3:2:1.5:1:1:0.5:0.5:0.5:1:1: Bupleurum chinense, Curcuma longa, Cyperus rotundus, Paeonia lactiflora, Boswellia carterii, Pinellia ternata, Fritillaria thunbergii, Prunella vulgaris, camphor oil, and turpentine oil. Use a grinder to grind the following ingredients into powder and pass them through a 40-mesh sieve to obtain the raw medicinal powder. Step A2: Add 70% ethanol solution to the raw medicinal material powder obtained in step A1 at a mass-volume ratio of 1 g: 8 mL, and extract by heating reflux at 80℃ for 2 h. After extraction, filter the extract and residue with a filter cloth to separate them. Add the same volume of 70% ethanol solution as the first extraction to the residue and extract again. Repeat the extraction and filtration 3 times. Combine the 3 extracts to obtain the combined extract. Step A3: Concentrate the combined extract obtained in step A2 using a rotary evaporator at a speed of 50 r / min and a heating temperature of 30℃. Connect the rotary evaporator to an ethanol cooling liquid circulation pump with the temperature of the ethanol cooling liquid circulation pump set to -10℃. Concentrate the combined extract until each milliliter of concentrate is equivalent to 3.5-4 g of raw medicinal material powder to obtain a traditional Chinese medicine compound extract concentrate. Step A4: Add the camphor essential oil and turpentine oil weighed in step A1 to the concentrated extract of traditional Chinese medicine compound obtained in step A3, and stir and mix for 20 minutes under a constant temperature magnetic stirrer at a stirring speed of 100 r / min to obtain the traditional Chinese medicine compound extract. This invention also provides a method for preparing a pharmaceutical preparation for treating breast hyperplasia, specifically comprising the following steps: (1): Weigh out microneedle matrix and purified water in a weight ratio of 0.4-1.5:2. Add the weighed microneedle matrix to the purified water and stir for 20 min under a constant temperature magnetic stirrer at a stirring speed of 80 r / min and a temperature of 45℃ to obtain microneedle matrix solution. (2): Weigh one part of the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir at 45°C for 10 min in a constant temperature magnetic stirrer and mix well. Stir at 150 r / min to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) was poured into the PDMS microneedle negative mold while hot, centrifuged at 4000 r / min for 20 min in a centrifuge to remove air bubbles, and the drug-loaded microneedle matrix solution was leveled with a plastic scraper and cured in a vacuum dryer at room temperature for 6 h to obtain the drug-loaded microneedle layer. (4): Weigh the backing matrix and purified water in a weight ratio of 0.2-0.6:2, add the weighed backing matrix to the purified water, and stir at 45°C for 20 min to dissolve it, with a stirring speed of 80 r / min, to obtain the backing matrix solution. (5): The backing matrix solution obtained in step (4) is poured into the PDMS microneedle negative mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation at 4000 r / min for 20 min, the excess backing matrix solution is scraped off. The backing matrix solution is cured in a vacuum dryer at room temperature for 12 h to obtain the backing layer connected to the drug-loaded microneedle layer. After drying, the backing matrix is ​​carefully demolded with tweezers to obtain the traditional Chinese medicine compound microneedles. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia. The beneficial effects achieved by this invention are as follows: The pharmaceutical preparation for treating breast hyperplasia prepared in this invention has positive effects on improving drug penetration and absorption, and promoting skin repair and regeneration. The herbs used, including *Bupleurum chinense*, *Curcuma longa*, and *Cyperus rotundus*, have liver-soothing and mood-lifting effects; *Fritillaria thunbergii* and *Pinellia ternata* have heat-clearing, phlegm-resolving, nodule-dispersing, and swelling-reducing effects, assisting in clearing blockages and softening hyperplastic tissue. These properties complement the heat-clearing and detoxifying effects of *Prunella vulgaris*, neutralizing the warming nature of other herbs and avoiding excessive skin irritation. The compound formula also includes *Paeonia lactiflora* and *Pinellia ternata*, which improve drug penetration. The interaction of paeoniflorin and gingerol effectively reduces the irritation caused by other components. This designed traditional Chinese medicine compound emphasizes holistic regulation, achieving multiple effects such as regulating endocrine function, soothing the liver and regulating qi, promoting blood circulation and removing blood stasis, reducing swelling and nodules, and anti-inflammatory and analgesic effects. The drug-loaded microneedle layer, prepared from a soluble microneedle matrix and a traditional Chinese medicine compound ointment, possesses sufficient mechanical strength to effectively penetrate the stratum corneum and epidermis without touching pain nerves. The selected microneedle matrix maintains a gel-like network structure under the skin, enabling the sustained and efficient delivery of active ingredients such as saponins, flavonoids, and alkaloids from the traditional Chinese medicine compound ointment to the lesions of breast hyperplasia, maintaining effective concentrations for a prolonged period and exerting a sustained therapeutic effect. Furthermore, the essential oils and volatile oils in the traditional Chinese medicine compound ointment not only promote the penetration of lipid-soluble components into the deep layers of the skin but also readily form a microemulsion system in the hydrophilic environment of the microneedle matrix. This system helps maintain skin hydration, providing moisturizing, anti-inflammatory, antibacterial, and antioxidant effects, and offering a favorable microenvironment for skin cell repair. The presence of the backing layer forms a barrier, effectively preventing the drug in the microneedles from diffusing into the adhesive tape, minimizing loss. Compared to traditional oral or injection treatments, microneedle patches are non-invasive and easy to use. They also avoid adverse reactions caused by drug metabolism in the gastrointestinal tract, increase blood drug concentration, and have high safety, making them suitable for patients with breast hyperplasia. Compared with existing technologies, this invention provides a safe, effective, and convenient treatment plan for breast hyperplasia through the compatibility of effective ingredients and the application of microneedle technology, which has significant clinical application value. Attached Figure Description Figure 1 is a flowchart of the preparation of a pharmaceutical formulation for treating breast hyperplasia according to the present invention; Figure 2 is a schematic diagram of the structural composition of a pharmaceutical preparation for treating breast hyperplasia according to the present invention; Figure 3 is a magnified view of a single microneedle in part A of Figure 2; Figure 4 shows the force-displacement curves of a pharmaceutical preparation for treating breast hyperplasia prepared in Examples 1-6; Figure 5 is a scanning electron microscope image of a pharmaceutical preparation for treating breast hyperplasia prepared in Example 6; Figure 6 shows the H&E staining results of porcine skin sections prepared using a pharmaceutical formulation for treating mammary hyperplasia prepared in Examples 2-4 and Example 6. Among them, 1, Chinese herbal compound microneedle patch; 2, drug-loaded microneedle layer; 201, Chinese herbal compound ointment; 202, microneedle matrix solution; 3, backing layer; 4, medical blank adhesive tape; a, b, c and d are respectively H&E tissue staining images of pig skin sections after applying the Chinese herbal compound microneedle patch prepared in Examples 2-4 and Example 6. The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. Detailed Implementation The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application. The preparation process in the following examples is shown in Figure 1. The structure of the prepared drug formulation for treating breast hyperplasia is shown in Figure 2. The composition of a single microneedle is shown in Figure 3. Unless otherwise specified, all methods are conventional. Unless otherwise specified, all materials used in the following examples are new materials purchased from the market. The present invention provides a pharmaceutical preparation for treating breast hyperplasia, the pharmaceutical preparation comprising a drug-loaded microneedle layer, a backing layer in contact with the drug-loaded microneedle layer, and a medical blank adhesive tape for adhering to the backing layer. The drug-loaded microneedle layer is prepared from the following raw materials: traditional Chinese medicine compound extract, microneedle matrix and purified water. The traditional Chinese medicine compound ointment is prepared from the following raw materials: Bupleurum chinense, Curcuma longa, Cyperus rotundus, Paeonia lactiflora, Boswellia carterii, Pinellia ternata, Fritillaria thunbergii, Prunella vulgaris, camphor oil, turpentine oil and 70% ethanol solution. The backing layer is prepared from the following raw materials: backing layer matrix and purified water. The preparation method of the traditional Chinese medicine compound extract includes the following steps: Step A1: Weigh out the following ingredients in a weight ratio of 3:2:1.5:1:1:0.5:0.5:0.5:1:1: Bupleurum chinense, Curcuma longa, Cyperus rotundus, Paeonia lactiflora, Boswellia carterii, Pinellia ternata, Fritillaria thunbergii, Prunella vulgaris, camphor oil, and turpentine oil. Use a grinder to grind the following ingredients into powder and pass them through a 40-mesh sieve to obtain the raw medicinal powder. Step A2: Add 70% ethanol solution to the raw medicinal material powder obtained in step A1 at a mass-volume ratio of 1 g: 8 mL, and extract by heating reflux at 80℃ for 2 h. After extraction, filter the extract and residue with a filter cloth to separate them. Add the same volume of 70% ethanol solution as the first extraction to the residue and extract again. Repeat the extraction and filtration 3 times. Combine the 3 extracts to obtain the combined extract. Step A3: Concentrate the combined extract obtained in step A2 using a rotary evaporator at a speed of 50 r / min and a heating temperature of 30℃. Connect the rotary evaporator to an ethanol cooling liquid circulation pump with the temperature of the ethanol cooling liquid circulation pump set to -10℃. Concentrate the combined extract until each milliliter of concentrate is equivalent to 3.5-4 g of raw medicinal material powder to obtain a traditional Chinese medicine compound extract concentrate. Step A4: Add the camphor essential oil and turpentine oil weighed in step A1 to the concentrated extract of traditional Chinese medicine compound obtained in step A3, and stir and mix for 20 minutes under a constant temperature magnetic stirrer at a stirring speed of 100 r / min to obtain the traditional Chinese medicine compound extract. This invention also provides a method for preparing a pharmaceutical preparation for treating breast hyperplasia, specifically comprising the following steps: (1): Weigh out microneedle matrix and purified water in a weight ratio of 0.4-1.5:2. Add the weighed microneedle matrix to the purified water and stir for 20 min under a constant temperature magnetic stirrer at a stirring speed of 80 r / min and a temperature of 45℃ to obtain microneedle matrix solution. (2): Weigh one part of the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir at 45°C for 10 min in a constant temperature magnetic stirrer and mix well. Stir at 150 r / min to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) was poured into the PDMS microneedle negative mold while hot, centrifuged at 4000 r / min for 20 min in a centrifuge to remove air bubbles, and the drug-loaded microneedle matrix solution was leveled with a plastic scraper and cured in a vacuum dryer at room temperature for 6 h to obtain the drug-loaded microneedle layer. (4): Weigh the backing matrix and purified water in a weight ratio of 0.2-0.6:2, add the weighed backing matrix to the purified water, and stir at 45°C for 20 min to dissolve it, with a stirring speed of 80 r / min, to obtain the backing matrix solution. (5): The backing matrix solution obtained in step (4) is poured into the PDMS microneedle negative mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation at 4000 r / min for 20 min, the excess backing matrix solution is scraped off. The backing matrix solution is cured in a vacuum dryer at room temperature for 12 h to obtain the backing layer connected to the drug-loaded microneedle layer. After drying, the backing matrix is ​​carefully demolded with tweezers to obtain the traditional Chinese medicine compound microneedles. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia. By selecting a single microneedle matrix or a combination of multiple microneedle matrices to load traditional Chinese medicine compound ointment, soluble drug-loaded microneedle layers with different appearances, mechanical properties, and hygroscopicities are prepared, thereby obtaining traditional Chinese medicine compound microneedle patches with different drug loading capacity and skin puncture capabilities. The formulation examples are shown in Table 1. Table 1. Prescription composition of traditional Chinese medicine compound microneedle patch Example 1: This example uses the raw material composition ratio of group 1 in Table 1 to provide a pharmaceutical preparation for treating breast hyperplasia, including a drug-loaded microneedle layer, a backing layer connected to the drug-loaded microneedle layer, and a blank medical adhesive tape for adhering to the backing layer. The components are 1 part by weight of traditional Chinese medicine compound extract, 0.4 parts by weight of PVP K90, and 0.2 parts by weight of HA. This embodiment also provides a method for preparing a pharmaceutical preparation for treating breast hyperplasia, specifically including the following steps: (1): Weigh 0.4 parts of PVP K90 and add it to 2 parts of purified water. Stir for 20 min under a constant temperature magnetic stirrer at a stirring speed of 80 r / min and a temperature of 45℃ to obtain a microneedle matrix solution. (2): Weigh one part of the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir at 45°C for 10 min in a constant temperature magnetic stirrer and mix well. Stir at 150 r / min to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) was poured into the PDMS microneedle negative mold while hot, centrifuged at 4000 r / min for 20 min in a centrifuge to remove air bubbles, and the drug-loaded microneedle matrix solution was leveled with a plastic scraper and cured in a vacuum dryer at room temperature for 6 h to obtain the drug-loaded microneedle layer. (4): Weigh 0.2 parts of HA, add it to 2 parts of purified water, and stir at 45°C for 20 min to dissolve it. The stirring speed is 80 r / min to obtain the backing matrix solution. (5): The backing matrix solution obtained in step (4) is poured into the PDMS microneedle negative mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation at 4000 r / min for 20 min, the excess backing matrix solution is scraped off. The backing matrix solution is cured in a vacuum dryer at room temperature for 12 h to obtain the backing layer connected to the drug-loaded microneedle layer. After drying, the backing matrix is ​​carefully demolded with tweezers to obtain the traditional Chinese medicine compound microneedles. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia. Example 2: This example uses the raw material composition ratio of group 2 in Table 1 to provide a pharmaceutical preparation for treating breast hyperplasia, including a drug-loaded microneedle layer, a backing layer in contact with the drug-loaded microneedle layer, and a blank medical adhesive tape for adhering to the backing layer. The components are 1 part by weight of traditional Chinese medicine compound extract, 1 part by weight of PVP K90, and 0.4 parts by weight of HA. This embodiment also provides a method for preparing a pharmaceutical preparation for treating breast hyperplasia, specifically including the following steps: (1): Weigh 1 part of PVP K90 and add it to 2 parts of purified water. Stir for 20 min under a constant temperature magnetic stirrer at a stirring speed of 80 r / min and a temperature of 45℃ to obtain a microneedle matrix solution. (2): Weigh one part of the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir at 45°C for 10 min in a constant temperature magnetic stirrer and mix well. Stir at 150 r / min to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) was poured into the PDMS microneedle negative mold while hot, centrifuged at 4000 r / min for 20 min in a centrifuge to remove air bubbles, and the drug-loaded microneedle matrix solution was leveled with a plastic scraper and cured in a vacuum dryer at room temperature for 6 h to obtain the drug-loaded microneedle layer. (4): Weigh 0.4 parts of HA, add it to 2 parts of purified water, and stir at 45°C for 20 min to dissolve it. The stirring speed is 80 r / min to obtain the backing matrix solution. (5): The backing matrix solution obtained in step (4) is poured into the PDMS microneedle negative mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation at 4000 r / min for 20 min, the excess backing matrix solution is scraped off. The backing matrix solution is cured in a vacuum dryer at room temperature for 12 h to obtain the backing layer connected to the drug-loaded microneedle layer. After drying, the backing matrix is ​​carefully demolded with tweezers to obtain the traditional Chinese medicine compound microneedles. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia. Example 3: This example uses the raw material composition ratio of group 3 in Table 1 to provide a pharmaceutical preparation for treating breast hyperplasia, including a drug-loaded microneedle layer, a backing layer connected to the drug-loaded microneedle layer, and a blank medical adhesive tape for adhering to the backing layer. The components are 1 part by weight of traditional Chinese medicine compound extract, 0.5 parts by weight of PVP K90, 0.5 parts by weight of CMC-Na, and 0.4 parts by weight of HA. This embodiment also provides a method for preparing a pharmaceutical preparation for treating breast hyperplasia, specifically including the following steps: (1): Weigh 0.5 parts of PVP K90 and 0.5 parts of CMC-Na, add them to 2 parts of purified water, and stir for 20 min under a constant temperature magnetic stirrer at a stirring speed of 80 r / min and a temperature of 45℃ to obtain a microneedle matrix solution. (2): Weigh one part of the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir at 45°C for 10 min in a constant temperature magnetic stirrer and mix well. Stir at 150 r / min to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) was poured into the PDMS microneedle negative mold while hot, centrifuged at 4000 r / min for 20 min in a centrifuge to remove air bubbles, and the drug-loaded microneedle matrix solution was leveled with a plastic scraper and cured in a vacuum dryer at room temperature for 6 h to obtain the drug-loaded microneedle layer. (4): Weigh 0.4 parts of HA, add it to 2 parts of purified water, and stir at 45°C for 20 min to dissolve it. The stirring speed is 80 r / min to obtain the backing matrix solution. (5): The backing matrix solution obtained in step (4) is poured into the PDMS microneedle negative mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation at 4000 r / min for 20 min, the excess backing matrix solution is scraped off. The backing matrix solution is cured in a vacuum dryer at room temperature for 12 h to obtain the backing layer connected to the drug-loaded microneedle layer. After drying, the backing matrix is ​​carefully demolded with tweezers to obtain the traditional Chinese medicine compound microneedles. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia. Example 4: This example uses the raw material composition ratio of group 4 in Table 1 to provide a pharmaceutical preparation for treating breast hyperplasia, including a drug-loaded microneedle layer, a backing layer connected to the drug-loaded microneedle layer, and a blank medical adhesive tape for adhering to the backing layer. The components are 1 part by weight of traditional Chinese medicine compound extract, 0.5 parts by weight of PVP K90, 0.5 parts by weight of CS, and 0.4 parts by weight of HA. This embodiment also provides a method for preparing a pharmaceutical preparation for treating breast hyperplasia, specifically including the following steps: (1): Weigh 0.5 parts of PVP K90 and 0.5 parts of CS, add them to 2 parts of purified water, and stir for 20 min under a constant temperature magnetic stirrer to dissolve them. The stirring speed is 80 r / min and the temperature is 45℃ to obtain a microneedle matrix solution. (2): Weigh one part of the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir at 45°C for 10 min in a constant temperature magnetic stirrer and mix well. Stir at 150 r / min to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) was poured into the PDMS microneedle negative mold while hot, centrifuged at 4000 r / min for 20 min in a centrifuge to remove air bubbles, and the drug-loaded microneedle matrix solution was leveled with a plastic scraper and cured in a vacuum dryer at room temperature for 6 h to obtain the drug-loaded microneedle layer. (4): Weigh 0.4 parts of HA, add it to 2 parts of purified water, and stir at 45°C for 20 min to dissolve it. The stirring speed is 80 r / min to obtain the backing matrix solution. (5): The backing matrix solution obtained in step (4) is poured into the PDMS microneedle negative mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation at 4000 r / min for 20 min, the excess backing matrix solution is scraped off. The backing matrix solution is cured in a vacuum dryer at room temperature for 12 h to obtain the backing layer connected to the drug-loaded microneedle layer. After drying, the backing matrix is ​​carefully demolded with tweezers to obtain the traditional Chinese medicine compound microneedles. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia. Example 5: This example uses the raw material composition ratio of group 5 in Table 1 to provide a pharmaceutical preparation for treating breast hyperplasia, including a drug-loaded microneedle layer, a backing layer connected to the drug-loaded microneedle layer, and a blank medical adhesive tape for adhering to the backing layer. The components are 1 part by weight of traditional Chinese medicine compound extract, 0.2 parts by weight of PVP K90, 0.2 parts by weight of Gantrez AN-139, and 0.2 parts by weight of HA. This embodiment also provides a method for preparing a pharmaceutical preparation for treating breast hyperplasia, specifically including the following steps: (1): Weigh 0.2 parts of PVP K90 and 0.2 parts of Gantrez AN-139, add them to 2 parts of purified water, and stir for 20 min under a constant temperature magnetic stirrer at a stirring speed of 80 r / min and a temperature of 45℃ to obtain a microneedle matrix solution. (2): Weigh one part of the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir at 45°C for 10 min in a constant temperature magnetic stirrer and mix well. Stir at 150 r / min to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) was poured into the PDMS microneedle negative mold while hot, centrifuged at 4000 r / min for 20 min in a centrifuge to remove air bubbles, and the drug-loaded microneedle matrix solution was leveled with a plastic scraper and cured in a vacuum dryer at room temperature for 6 h to obtain the drug-loaded microneedle layer. (4): Weigh 0.2 parts of HA, add it to 2 parts of purified water, and stir at 45°C for 20 min to dissolve it. The stirring speed is 80 r / min to obtain the backing matrix solution. (5): The backing matrix solution obtained in step (4) is poured into the PDMS microneedle negative mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation at 4000 r / min for 20 min, the excess backing matrix solution is scraped off. The backing matrix solution is cured in a vacuum dryer at room temperature for 12 h to obtain the backing layer connected to the drug-loaded microneedle layer. After drying, the backing matrix is ​​carefully demolded with tweezers to obtain the traditional Chinese medicine compound microneedles. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia. Example 6: This example uses the raw material composition ratio of group 6 in Table 1 to provide a pharmaceutical preparation for treating breast hyperplasia, including a drug-loaded microneedle layer, a backing layer in contact with the drug-loaded microneedle layer, and a blank medical adhesive tape for adhering to the backing layer. The components are 1 part by weight of traditional Chinese medicine compound extract, 0.5 parts by weight of PVP K90, 0.5 parts by weight of Gantrez AN-139, and 0.4 parts by weight of HA. This embodiment also provides a method for preparing a pharmaceutical preparation for treating breast hyperplasia, specifically including the following steps: (1): Weigh 0.5 parts of PVP K90 and 0.5 parts of Gantrez AN-139, add them to 2 parts of purified water, and stir for 20 min under a constant temperature magnetic stirrer at a stirring speed of 80 r / min and a temperature of 45℃ to obtain a microneedle matrix solution. (2): Weigh one part of the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir at 45°C for 10 min in a constant temperature magnetic stirrer and mix well. Stir at 150 r / min to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) was poured into the PDMS microneedle negative mold while hot, centrifuged at 4000 r / min for 20 min in a centrifuge to remove air bubbles, and the drug-loaded microneedle matrix solution was leveled with a plastic scraper and cured in a vacuum dryer at room temperature for 6 h to obtain the drug-loaded microneedle layer. (4): Weigh 0.4 parts of HA, add it to 2 parts of purified water, and stir at 45°C for 20 min to dissolve it. The stirring speed is 80 r / min to obtain the backing matrix solution. (5): The backing matrix solution obtained in step (4) is poured into the PDMS microneedle negative mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation at 4000 r / min for 20 min, the excess backing matrix solution is scraped off. The backing matrix solution is cured in a vacuum dryer at room temperature for 12 h to obtain the backing layer connected to the drug-loaded microneedle layer. After drying, the backing matrix is ​​carefully demolded with tweezers to obtain the traditional Chinese medicine compound microneedles. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia. Example 7: This example uses the raw material composition ratio of group 7 in Table 1 to provide a pharmaceutical preparation for treating breast hyperplasia, including a drug-loaded microneedle layer, a backing layer in contact with the drug-loaded microneedle layer, and a blank medical adhesive tape for adhering to the backing layer. The components are 1 part by weight of traditional Chinese medicine compound extract, 1 part by weight of PVP K90, 0.5 parts by weight of Gantrez AN-139, and 0.6 parts by weight of HA. This embodiment also provides a method for preparing a pharmaceutical preparation for treating breast hyperplasia, specifically including the following steps: (1): Weigh 1 part PVP K90 and 0.5 parts Gantrez AN-139, add them to 2 parts purified water, and stir for 20 min under a constant temperature magnetic stirrer at a stirring speed of 80 r / min and a temperature of 45℃ to obtain a microneedle matrix solution. (2): Weigh one part of the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir at 45°C for 10 min in a constant temperature magnetic stirrer and mix well. Stir at 150 r / min to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) was poured into the PDMS microneedle negative mold while hot, centrifuged at 4000 r / min for 20 min in a centrifuge to remove air bubbles, and the drug-loaded microneedle matrix solution was leveled with a plastic scraper and cured in a vacuum dryer at room temperature for 6 h to obtain the drug-loaded microneedle layer. (4): Weigh 0.6 parts of HA, add 2 parts of purified water, and stir at 45°C for 20 min to dissolve the HA. The stirring speed is 80 r / min to obtain the backing matrix solution. (5): The backing matrix solution obtained in step (4) is poured into the PDMS microneedle negative mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation at 4000 r / min for 20 min, the excess backing matrix solution is scraped off. The backing matrix solution is cured in a vacuum dryer at room temperature for 12 h to obtain the backing layer connected to the drug-loaded microneedle layer. After drying, the backing matrix is ​​carefully demolded with tweezers to obtain the traditional Chinese medicine compound microneedles. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia. Microneedle property investigation The drug formulations for treating breast hyperplasia prepared in Examples 1-6 were used to observe the microneedle arrays, needle integrity, and ease of demolding prepared with different microneedle matrix compositions using both naked eye and microscope. The results are shown in Table 2. Mechanical property testing The mechanical strength of the microneedles in the pharmaceutical formulations for treating breast hyperplasia prepared in Examples 1-6 was evaluated using a texture analyzer. After drying, each group of microneedles was cut into 5×5 microneedle arrays using a scalpel for measurement. The program was set to a single compression, with the sensor moving from top to bottom to contact the needle tip. When the bottom of the sensor contacted the top of the microneedle, the sensor travel and the force applied to the microneedle were recorded. Parameters were set as follows: maximum force 100 N, initial force 0.15% (0.15 N) of the maximum force, deformation fraction 80% (i.e., 480 μm), and probe downward speed 0.04 mm / s. The instrument recorded the microneedle fracture force, and force-displacement curves were plotted to compare the differences in mechanical strength of microneedles prepared with different microneedle matrix compositions. The results are shown in Figure 4. Micromorphological observation The drug formulation for treating breast hyperplasia prepared in Example 6 was fixed onto a sample plate using conductive adhesive, gold was deposited using a sputtering coating machine, and the morphology of the microneedles was examined using a scanning electron microscope. The results are shown in Figure 5. Skin puncture capability assessment The skin puncture capability of the pharmaceutical preparations for treating breast hyperplasia prepared in Examples 2-4 and Example 6 were investigated using the H&E tissue section method. A piece of pigskin was taken, its surface hair was shaved off, and it was cut into four pieces. The traditional Chinese medicine compound microneedle patches prepared in Examples 2-4 and Example 6 were applied to each piece for 3 minutes. The skin at the microneedle location was then excised, fixed in 4% paraformaldehyde solution, embedded in liquid paraffin, and sectioned. The sections were stained with hematoxylin and eosin and observed under a microscope to observe the degree of microneedle penetration. The staining results of the tissue sections are shown in Figure 6. Table 2 Properties of Microneedles Table 2 shows that the drug formulations for treating breast hyperplasia prepared in Examples 5-7 have good molding effects and are easy to demold. Combined with the force-displacement curve results in Figure 4, the composite microneedle matrix has higher mechanical strength than the single matrix and is less likely to remain on the mold. Figure 5 shows that the microneedles in the drug formulation for treating breast hyperplasia prepared in Example 6 are conical, straight, without collapse or defects, and each microneedle has a uniform morphology. The H&E tissue staining results in Figure 6 show that the drug preparations for treating breast hyperplasia prepared in Examples 2-4 and Example 6 can effectively penetrate the stratum corneum and epidermis without reaching the nerve endings in the dermis, thus achieving painless drug delivery. In summary, the test results of the embodiments show that the drug preparation for treating breast hyperplasia prepared by the present invention delivers the effective active ingredients of the traditional Chinese medicine compound to the hyperplastic lesion site in the form of a microneedle patch, thereby increasing the local drug concentration, avoiding the first-pass effect after oral administration, and achieving a rapid therapeutic effect. At the same time, compared with intravenous injection, the patient compliance is good and there is no pain. Furthermore, the soluble microneedle matrix used has good biocompatibility, dissolves and releases the drug after piercing the skin, and does not leave any residue in the body. Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents. The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A pharmaceutical preparation for treating breast hyperplasia, characterized in that, It includes a drug-loaded microneedle layer, a backing layer connected to the drug-loaded microneedle layer, and a blank medical adhesive tape for adhering to the backing layer; The drug-loaded microneedle layer is prepared from the following raw materials: traditional Chinese medicine compound extract, microneedle matrix and purified water; The traditional Chinese medicine compound ointment is prepared from the following raw materials: Bupleurum chinense, Curcuma longa, Cyperus rotundus, Paeonia lactiflora, Boswellia carterii, Pinellia ternata, Fritillaria thunbergii, Prunella vulgaris, camphor oil, turpentine oil and 70% ethanol solution; The backing layer is prepared from the following raw materials: backing layer matrix and purified water; The weight ratio of the herbal compound ointment, microneedle matrix, and backing matrix is ​​1:0.4-1.5:0.2-0.

6.

2. The pharmaceutical preparation for treating breast hyperplasia according to claim 1, characterized in that, The preparation method of the traditional Chinese medicine compound extract includes the following steps: Step A1: Weigh out Bupleurum chinense, Curcuma longa, Cyperus rotundus, Paeonia lactiflora, Boswellia carterii, Pinellia ternata, Fritillaria thunbergii and Prunella vulgaris, pulverize and sieve to obtain raw medicinal powder; Step A2: Add 70% ethanol solution to the raw medicinal material powder obtained in step A1, heat and extract, separate the extract and filter residue, add 70% ethanol solution to the filter residue and extract repeatedly, then combine the extracts to obtain the combined extract; Step A3: Concentrate the combined extract obtained in step A2 to obtain a concentrated extract of traditional Chinese medicine compound extract; Step A4: Weigh out camphor essential oil and turpentine oil, add them to the concentrated extract of traditional Chinese medicine compound obtained in step A3, stir and mix well to obtain traditional Chinese medicine compound extract.

3. The pharmaceutical preparation for treating breast hyperplasia according to claim 2, characterized in that, The weight ratio of the following herbs is 3:2:1.5:1:1:0.5:0.5:0.5:1:1; In step A1, the pulverizing process uses a pulverizer, and the sieve screen is 40 mesh. In step A2, the mass-volume ratio of the crude medicinal material powder and the 70% ethanol solution is 1 g: 8 mL. The extraction is carried out by heating and reflux at 80°C for 2 hours. The separation process uses a filter cloth and is repeated 3 times, with the same volume of 70% ethanol solution added each time. In step A3, the concentration process uses a rotary evaporator with a rotation speed of 50 r / min and a heating temperature of 30°C. The rotary evaporator is connected to an ethanol cooling liquid circulation pump with the temperature set to -10°C. In step A4, the stirring process is carried out under a constant temperature magnetic stirrer for 20 minutes at a speed of 100 r / min.

4. A method for preparing a pharmaceutical preparation for treating breast hyperplasia according to any one of claims 1-3, characterized in that, Includes the following steps: (1): Weigh out the microneedle matrix and dissolve it in purified water to obtain a microneedle matrix solution; (2): Weigh out the compound Chinese medicine extract and add it to the microneedle matrix solution obtained in step (1). Stir and mix well to obtain the drug-loaded microneedle matrix solution. (3): The drug-loaded microneedle matrix solution obtained in step (2) is poured into the mold while hot, centrifuged to remove air bubbles, scraped flat and solidified to obtain the drug-loaded microneedle layer; (4): Weigh the backing matrix and dissolve it in purified water to obtain the backing matrix solution; (5): The backing matrix solution obtained in step (4) is poured into the mold containing the drug-loaded microneedle layer in step (3) while it is still hot. After centrifugation and leveling, it is solidified to obtain the backing layer connected to the drug-loaded microneedle layer. After demolding, the traditional Chinese medicine compound microneedles are obtained. (6): Adhere one side of the Chinese herbal compound microneedle backing layer obtained in step (5) to the adhesive side of a blank medical adhesive tape to obtain the Chinese herbal compound microneedle patch, which is a drug preparation for treating breast hyperplasia.

5. A method for preparing a pharmaceutical preparation for treating breast hyperplasia according to claim 4, characterized in that, The weight ratio of microneedle matrix to purified water in steps (1) and (4) is 0.4-1.5:2, the weight ratio of backing matrix to purified water is 0.2-0.6:2, and the dissolution process is carried out under a constant temperature magnetic stirrer for 20 min, 80 r / min, and 45℃. In step (2), the stirring process is carried out under a constant temperature magnetic stirrer for 10 min, with a speed of 150 r / min and a temperature of 45℃. In steps (3) and (5), the centrifugation process uses a centrifuge, the centrifugation time is 20 min, the centrifugation speed is 4000 r / min, and the curing process is carried out in a vacuum dryer at room temperature. The curing time in step (3) is 6 h, and the curing time in step (5) is 12 h.

6. A method for preparing a pharmaceutical preparation for treating breast hyperplasia according to claim 5, characterized in that, The mold is a PDMS microneedle negative mold.

7. A method for preparing a pharmaceutical preparation for treating breast hyperplasia according to claim 6, characterized in that, The microneedle matrix is ​​selected from one or more of CMC-Na, CS, silk fibroin, PVP K90, and Gantrez AN-139, and the backing matrix is ​​selected from one of HA, HPMC, and PVA.

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