Soluble microneedle acupoint sticking based on traditional chinese medicine ingredient self-carrier, preparation method and application thereof

Abstract

The application belongs to the technical field of medicine and disease treatment, and particularly relates to a soluble microneedle acupoint patch based on a traditional Chinese medicine component self-carrier, a preparation method and application thereof. The soluble microneedle acupoint patch comprises a base layer and a microneedle array composed of microneedles, and a soluble polymer matrix is added as a connecting layer between the two; the material adopted by the base layer is sodium alginate and puerarin, the sodium alginate and the puerarin are mixed at a mass ratio of 2:5 to form the base layer; the microneedle comprises a traditional Chinese medicine active component, the traditional Chinese medicine active component is prepared from raw materials in the following mass fractions: 2-6 parts of curcumin extract, 50-150 parts of puerarin extract and 2-6 parts of berberine extract; and the soluble polymer matrix is sodium alginate. The soluble microneedle acupoint patch provided by the application can reduce the discomfort caused by traditional acupuncture, reduce the operation difficulty, reduce the potential toxic and side effects of oral or intravenous injection of drugs, and improve the patient compliance.

Description

Technical Field

[0001] This invention belongs to the field of drug and disease treatment technology, specifically relating to soluble microneedle acupoint patches based on self-carriers of traditional Chinese medicine components, their preparation methods, and applications. Background Technology

[0002] Obesity is a chronic metabolic disease caused by excessive accumulation of body fat, which significantly increases the risk of cardiovascular disease, type II diabetes, respiratory diseases, bone and joint diseases, and certain types of cancer.

[0003] Currently, treatments for obesity include fasting, medication, and surgical intervention. These methods suffer from slow effectiveness, significant side effects, complex procedures, and a high recurrence rate. Products that rationally construct and utilize active ingredients from traditional Chinese medicine can address these issues.

[0004] Existing active ingredients from traditional Chinese medicines used to treat obesity include curcumin, berberine, menthol, and capsaicin. However, these active ingredients suffer from low bioavailability. Therefore, a new strategy for treating obesity by improving the bioavailability of active ingredients from traditional Chinese medicines is needed. Summary of the Invention

[0005] To address the problem of low bioavailability of traditional Chinese medicine components used in the treatment of obesity in existing technologies, this invention provides a soluble microneedle acupoint patch based on a self-carrier of traditional Chinese medicine components, its preparation method, and its application. To achieve the above objectives, this invention adopts the following technical solution.

[0006] This invention provides a soluble microneedle acupoint patch based on the self-carrier of traditional Chinese medicine components, comprising a base layer and a microneedle array composed of microneedles, with a soluble polymer matrix added between the two as a connecting layer;

[0007] The base layer is made of sodium alginate and puerarin, which are mixed in a mass ratio of 2:5 to form the base layer.

[0008] The microneedles include active components of traditional Chinese medicine, which are made from the following raw materials in parts by weight.

[0009] Curcumin extract 2 to 6 parts, puerarin extract 50 to 150 parts and berberine extract 2 to 6 parts.

[0010] The soluble polymer matrix includes sodium alginate, wherein the concentration of sodium alginate is 18 mg / mL to 22 mg / mL and the molecular weight is 198.11.

[0011] The soluble microneedle acupoint patch provided by this invention comprises a base layer and a microneedle array composed of microneedles, with a soluble polymer matrix added between the two as a connecting layer. The base layer is mainly composed of sodium alginate and puerarin. The presence of covalent bonding of amino and carboxyl groups, π-π stacking, and hydrophobic interactions between the two leads to cross-linking, forming a dense and stable cross-linked structure. The microneedles are rich in puerarin, curcumin, and berberine. Through numerous hydrophobic interactions, π-π stacking, and the interconnection of sugar chains, intermolecular forces are provided to form a rigid, soluble microneedle matrix. Due to the simultaneous presence of puerarin in the microneedle matrix and the base layer, the microneedles cross-link with the base layer to form the final microneedle structure, thus constituting the soluble microneedle acupoint patch. The soluble microneedles provided by this invention are entirely composed of traditional Chinese medicine components, eliminating the need for other cross-linking agents as carriers. This achieves the goal of integrating the carrier and drug components, enabling transdermal drug delivery and allowing the entire product to act as a drug on cells after dissolving at acupoints in vivo, greatly improving the bioavailability of traditional Chinese medicine components.

[0012] Using microneedle arrays as drug delivery carriers is a common strategy. Microneedles can penetrate the skin with pressure, delivering drugs directly and minimally invasively to acupoints, significantly improving bioavailability and acupoint concentration. However, delivering traditional Chinese medicine components via microneedles requires preparing different microneedles based on their physicochemical properties before drug loading, increasing operational complexity. Furthermore, for some metal microneedles, tip breakage and inflammation are possible, posing potential biosafety risks. However, the soluble microneedle acupoint patch provided by this invention avoids these problems. Moreover, the microneedles are mainly composed of traditional Chinese medicine components, eliminating the need for additional materials in microneedle preparation, thus integrating the microneedles and drug. This simplifies the preparation process and reduces biosafety risks.

[0013] Preferably, the active ingredient of the traditional Chinese medicine is made from the following raw materials in parts by weight:

[0014] 3 to 5 parts curcumin extract, 40 to 60 parts puerarin extract and 3 to 5 parts berberine extract.

[0015] Preferably, the active ingredient of the traditional Chinese medicine is made from the following raw materials in parts by weight:

[0016] Four parts of curcumin extract, 50 parts of puerarin extract, and four parts of berberine extract.

[0017] Preferably, the preparation method of the curcumin extract includes the following steps:

[0018] The curcumin was dissolved in an extraction solvent and extracted using ultrasound to obtain the curcumin extract.

[0019] The mass ratio of curcumin to the volume ratio of the extraction solvent is 1 mg to 3 mg: 1 mL.

[0020] Preferably, the preparation method of the berberine extract includes the following steps:

[0021] Berberine was dissolved in an extraction solvent and extracted using ultrasound to obtain the berberine extract.

[0022] The mass ratio of berberine to the volume ratio of the extraction solvent is 1 mg to 3 mg: 1 mL.

[0023] Preferably, the extraction solvent is a mixed solution of ethanol and water in a volume ratio of 1:1.

[0024] Preferably, the preparation method of the puerarin extract includes the following steps:

[0025] Puerarin was dissolved in water, heated to aid dissolution, and extracted to obtain the puerarin extract.

[0026] The mass ratio of puerarin to water is 40 mg to 60 mg: 1 mL.

[0027] The heating temperature for aiding dissolution is 99°C to 101°C. More preferably, the heating temperature for aiding dissolution is 100°C.

[0028] The present invention also provides a method for preparing the soluble microneedle acupoint patch, comprising the following steps:

[0029] The curcumin extract and the berberine extract were added to the puerarin extract to obtain a mixed solution; the mass ratio of the curcumin extract, the berberine extract and the puerarin extract was 1~3:1~3:50.

[0030] Subsequently, sodium alginate was added to the mixed solution, the temperature was maintained at 90°C~120°C, and after reacting for 15min~10min, it was cooled to 42°C~50°C, transferred to a mold, and the mold was placed in a vacuum environment for drying. After demolding, a microneedle array was constructed to obtain the soluble microneedle acupoint patch.

[0031] The mass ratio of sodium alginate to the volume ratio of the mixed solution is 10 mg to 30 mg: 3 mL.

[0032] This invention constructs a microneedle array in one step through the interaction of the active molecules of traditional Chinese medicine, without the need for additional materials as microneedle carriers, which greatly simplifies the preparation process and improves biocompatibility and bioavailability.

[0033] The present invention also provides the application of the soluble microneedle acupoint patch in the preparation of products for treating obesity.

[0034] Preferably, the product for treating obesity further includes pharmaceutically acceptable excipients.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] 1. This invention provides a soluble microneedle acupoint patch based on a self-carrier of traditional Chinese medicine components. The soluble microneedle acupoint patch provided by this invention comprises a base layer and a microneedle array composed of microneedles, with a soluble polymer matrix added between the two as a connecting layer. The base layer is mainly composed of sodium alginate and puerarin. The presence of covalent bonding of amino and carboxyl groups, π-π stacking, and hydrophobic interactions between the two leads to cross-linking, forming a dense and stable cross-linked structure. The microneedles are rich in puerarin, curcumin, and berberine. Through numerous hydrophobic interactions, π-π stacking, and the interconnection of sugar chains, intermolecular forces are provided to form a rigid, soluble microneedle matrix. Due to the simultaneous presence of puerarin in the microneedle matrix and the base layer, the microneedles cross-link with the base layer to form the final microneedle structure, thus constituting the soluble microneedle acupoint patch. The soluble microneedles provided by this invention are composed entirely of traditional Chinese medicine ingredients and do not require other cross-linking agents as carriers. This achieves the goal of integrating the carrier and drug ingredients, enabling transdermal drug delivery and allowing the entire product to act as a drug on cells after dissolving at acupoints in the body, thus greatly improving the bioavailability of traditional Chinese medicine components.

[0037] 2. This invention constructs a microneedle array in one step through the interaction of the active molecules of traditional Chinese medicine, without the need for additional materials as microneedle carriers, which greatly simplifies the preparation process and improves biocompatibility and bioavailability.

[0038] 3. This invention completes the preparation of an integrated carrier of traditional Chinese medicine and microneedles and uses it for drug delivery at acupoints to achieve the effect of inhibiting obesity by reducing inflammation and browning of white adipose tissue. Attached Figure Description

[0039] Figure 1 Characterization of the gel and microneedles in this invention; wherein, Figure 1 Figure A in the diagram is a comparison between the gel and sol states, with Figure A1 representing the gel state and Figure A2 representing the sol state. Figure 1 Image B in the image is a picture of the actual microneedles; Figure 1 Image C in the figure is a microneedle scanning electron microscope image; Figure 1 Image D in the image is a magnified image obtained using a scanning electron microscope.

[0040] Figure 2 This invention validates the downregulation of pro-inflammatory factors (TNF-α, IL-1β) and upregulation of anti-inflammatory factor (IL-10) by microbes containing different drug concentrations; wherein, Figure 2Figure A in the diagram shows the detection of the pro-inflammatory factor TNF-α; Figure 2 Figure B in the diagram shows the detection of the pro-inflammatory factor IL-1β; Figure 2 Figure C in the diagram shows the detection of the anti-inflammatory factor IL-10.

[0041] Figure 3 This is a skin H&E section after transdermal treatment with composite microneedles in this invention.

[0042] Figure 4 This is a schematic diagram of the browning of leukocyte lipids under drug intervention in this invention.

[0043] Figure 5 This is a fluorescence image showing the change in drug uptake by 3T3 cells over time in this invention; wherein, Figure 5 Image A in the image is a bright-field image of the cell; Figure 5 Image B in the diagram shows the fluorescence imaging of the drug; Figure 5 Image C in the diagram represents an image of the cell nucleus; Figure 5 The D diagram in the middle is Figure 5 Figure B in the middle and Figure 5 The overlay image of C in the image.

[0044] Figure 6 This refers to the change in lipid droplet content before and after microneedle treatment in this invention; wherein, Figure 6 Figure A in the diagram shows the image before processing; Figure 6 Figure B in the image shows the processed result.

[0045] Figure 7 This represents the trend of fat accumulation in cells as a function of drug concentration in this invention.

[0046] Figure 8 This refers to the changes in the expression levels of obesity-related cytokines in this invention; wherein, Figure 8 Figure A in the diagram represents the mRNA expression level of UCP-1. Figure 8 Figure B in the diagram shows the mRNA expression level of PGC-1α; Figure 8 Figure C in the figure represents the mRNA expression level of PRDM16; Figure 8 The D-plot in the figure represents the mRNA expression level of PPARγ; Figure 8 The E-plot in the figure represents the mRNA expression level of AMPK; Figure 8 The F-plot in the figure represents the mRNA expression level of Adipsin; Figure 8 The G-plot in the figure represents the mRNA expression level of Resistin.

[0047] Figure 9 The figures represent the body length of mice in different treatment groups in this invention. The six mice, from left to right, correspond to the normal group, the obesity model group, the thread embedding weight loss group, the sham thread embedding group, the Western medicine group, and the microneedle group.

[0048] Figure 10 The images depict the body width of mice in different treatment groups in this invention. The six mice, from left to right, correspond to the normal group, the obesity model group, the thread embedding weight loss group, the sham thread embedding group, the Western medicine group, and the microneedle group.

[0049] Figure 11 These are actual images of adipose tissue from mice in different treatment groups in this invention; wherein, Figure 11 Figure A in the diagram shows the adipose tissue of a normal mouse. Figure 11 Figure B in the figure shows the adipose tissue of a drug-induced obesity model mouse. Figure 11 Figure C shows the adipose tissue of mice after treatment with soluble microneedle acupoint patches; the four samples, from left to right, correspond to the adipose tissue of the four mice serving as parallel controls in each group. Detailed Implementation

[0050] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments, but this should not be construed as limiting the invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art, and the materials, reagents, etc. used in the following embodiments are commercially available unless otherwise specified.

[0051] Example 1: Preparation and structural characterization of soluble microneedle acupoint patches based on self-carriers of traditional Chinese medicine components

[0052] I. Preparation of Soluble Microneedle Acupoint Patches Based on Self-Carriers of Traditional Chinese Medicine Components

[0053] 1. Dissolve 2 mg of curcumin in 1 mL of extraction solvent and use ultrasound to aid dissolution to obtain solution A, which is the curcumin extract.

[0054] The concentration of curcumin in solution A is 2 mg / mL.

[0055] The ultrasonic dissolution time was 10 minutes. The temperature for ultrasonic dissolution was maintained at 25°C.

[0056] The extraction solvent is a mixed solution of ethanol and ultrapure water in a volume ratio of 1:1.

[0057] Curcumin is a powdered solid, purchased from Aladdin Chemical Reagents website (CAS: 458-37-7, molecular weight: 368.38, molecular formula: C). 21 H 20 O6).

[0058] 2. Dissolve 2 mg of berberine in 1 mL of extraction solvent and use ultrasound to aid dissolution to obtain solution B, which is the berberine extract.

[0059] The concentration of berberine in solution B is 2 mg / mL.

[0060] The ultrasonic dissolution time was 10 minutes. The temperature for ultrasonic dissolution was maintained at 25°C.

[0061] The extraction solvent is a mixed solution of ethanol and ultrapure water in a volume ratio of 1:1.

[0062] Berberine is a powdered solid, purchased from Aladdin Chemical Reagents website (CAS: 2086-83-1, molecular weight: 336.37, molecular formula: C). 20 H 18 NO4).

[0063] 3. Dissolve 50 mg of puerarin in 3 mL of ultrapure water and heat to aid dissolution, to obtain solution C, which is the puerarin extract.

[0064] The concentration of puerarin in solution C was 16.7 mg / mL.

[0065] Puerarin is a powdered solid, purchased from Aladdin Chemical Reagents website (CAS: 3681-99-0, molecular weight: 416.38, molecular formula: C). 21 H 20 O9).

[0066] The heating temperature for dissolving is maintained at 100°C in an oil bath environment.

[0067] Heat for 10 minutes to aid dissolution, stirring slowly.

[0068] 4. Add 100µL of solution A and 100µL of solution B dropwise to solution C, followed by the addition of 20mg of sodium alginate to obtain an amorphous gel.

[0069] The temperature of solution C was maintained at 100 °C.

[0070] 5. After the amorphous gel reacts for 10 minutes, mixture D is obtained. Mixture D is transferred to a mold, the mold is placed in a vacuum environment for drying, demolded, and a microneedle array is constructed to obtain a soluble microneedle acupoint patch.

[0071] Mixture D was cooled to 45 °C after the reaction.

[0072] The volume of the above mixture D in the mold is 400 µL.

[0073] The mold is a 10×10 conical array.

[0074] Each microneedle in the mold is 600 µm long and has a bottom diameter of 300 µm.

[0075] It should be noted that mixture D was demolded after being kept in a vacuum environment for 40 minutes.

[0076] II. Structural Characterization of Soluble Microneedle Acupoint Patches Based on Self-Carriers of Traditional Chinese Medicine Components

[0077] 1. Add 1 mL of mixture D to a 10 mL flat-bottomed glass bottle and cool to room temperature. Take a picture, as shown. Figure 1 The figure is shown in Figure A1 of Figure A.

[0078] 2. Maintain mixture D at 45°C until it becomes a sol state, and observe the results. Figure 1 Figure A2 in Figure A.

[0079] 3. At 100°C, 400 µL of mixture D was added to a microneedle mold. The mold was a 10 cm × 10 cm conical array, with each microneedle being 600 µm long and 300 µm in diameter at the base. The mold was placed in a vacuum environment for 40 minutes before demolding, photographing, and obtaining the desired microneedle composition. Figure 1 Figure B in the diagram.

[0080] 4. Microneedle SEM imaging was performed using a JSM-6390LV SEM with a magnification of 65 and an electron beam energy of 5 keV. Figure 1 Image C in the image, enlarged 180 degrees (obtained by taking a photo later). Figure 1 The D diagram in the image.

[0081] Example 2: Efficacy evaluation of soluble microneedle acupoint patches based on self-carriers of traditional Chinese medicine components

[0082] 1. Using 2×10 4 Mouse macrophage line RAW264.7 was seeded into six-well plates and cultured for 24 h. In each six-well plate, only complete culture medium was added as a negative control, only lipopolysaccharide (LPS: 200 ng / μL) was added as a positive control, and LPS and different SA (sodium alginate) material patches (SA material control, 5 μg / mL, 10 μg / mL, and 25 μg / mL CC (curcumin + berberine)) were added as experimental groups. The plates were then co-cultured for another 24 h. The cell culture supernatant was collected, and the secretion levels of cytokines such as IL-10, TNF-α, and IL-1β were quantitatively detected using an ELISA kit (Beyotime Biotech Co., Ltd.). Figure 2 Figure A in the middle Figure 2 Figure B in the middle and Figure 2 Figure C in the diagram.

[0083] The mouse macrophage cell line RAW264.7 was derived from Wuhan Pronosei Life Science Technology Co., Ltd.

[0084] The complete culture medium was sourced / formulated by Wuhan Pronosei Life Science Technology Co., Ltd., and its main components included fetal bovine serum, L-glutamine, HEPES buffer, sodium bicarbonate, and penicillin-streptomycin.

[0085] CC is a drug component in soluble microneedle acupoint patches. Therefore, when verifying the inflammatory regulatory efficacy of soluble microneedle acupoint patches at the cellular level, this pharmacologically active component was selected for study. Results showed that compared to the untreated group (negative group), the LPS-treated group (positive group) had increased levels of pro-inflammatory cytokines (IL-10) and decreased levels of anti-inflammatory cytokines (TNF-α, IL-1). Compared to the positive group, different concentrations of CC treatment groups showed decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines. With increasing CC concentration, the decrease in pro-inflammatory cytokines increased, and the increase in anti-inflammatory cytokines increased. These results indicate that different concentrations of CC treatment can, to some extent, promote the expression of anti-inflammatory cytokines and inhibit the expression of pro-inflammatory cytokines (TNF-α, IL-1); CC concentration was positively correlated with changes in anti-inflammatory cytokines and negatively correlated with changes in pro-inflammatory cytokines.

[0086] 2. Take one one-month-old SPF-grade male C57BL / 6J mouse, remove hair from its back, apply soluble acupoint microneedles to the hair removal area, remove the microneedles after 1 minute, cut off the corresponding skin, and immediately immerse it in 4% paraformaldehyde (by volume) for 24 hours for fixation. Perform H&E staining, and observe under a light microscope to obtain... Figure 3 .

[0087] The one-month-old SPF-grade male C57BL / 6J mice were sourced from Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0088] 3. 3T3 cells were seeded in confocal microplates and cultured for 12 hours at 37 °C in a cell culture incubator containing 5% CO2. Serum-free medium containing 10 μg / mL curcumin and berberine was added to the microplates. Changes in intracellular fluorescence at 6, 12, and 24 hours were observed under a microscope to determine the time-dependent changes in drug molecule uptake by the cells, thus obtaining [the desired data]. Figure 5 .

[0089] The 3T3 cells were sourced from Wuhan Pronosei Life Science Technology Co., Ltd.

[0090] The serum-free culture medium for curcumin and berberine was sourced / formulated by Wuhan Pronosai Life Science Technology Co., Ltd.

[0091] The drug was labeled with red fluorescence, and the cell nucleus was labeled with blue fluorescence for cell localization. As shown in the figure, the intensity of red fluorescence in the cell gradually increased with the extension of time, indicating that the CC uptake of 3T3 cells is positively correlated with the culture time.

[0092] 4. Seed 3T3 cells separately into two confocal microplates and cultured for 12 h in a cell culture incubator at 37 °C with 5% CO2. Add serum-free medium containing 10 μg / mL curcumin and berberine to the microplates and co-culture for another 12 h. Induce adipogenesis by removing the complete adipogenesis differentiation medium from the wells and wash twice with 1×PBS. Cover the cell surface with 4% (v / v) neutral formaldehyde solution and fix the cells for 30 min. During cell fixation, prepare Oil Red O working solution (saturated Oil Red O solution: pure water = 3:2, mixed well and filtered through neutral filter paper to remove impurities). Remove the 4% neutral formaldehyde solution and wash twice with 1×PBS. Add 1 mL of Oil Red O working solution to each microplate and stain at room temperature for 30 min. Remove the Oil Red O working solution, wash twice with 1×PBS to remove background impurities, and observe and photograph under a laser scanning confocal microscope to obtain the desired results. Figure 6 .

[0093] The saturated red oil O stain solution (10 mL) was purchased from Wuhan Pronosei Life Science Technology Co., Ltd.

[0094] As shown in the figure, the red signal in the cells was significantly reduced after CC treatment, indicating that CC treatment can effectively reduce the content of lipid droplets in the cells.

[0095] 5. The intensity of red color in cells after treatment with different concentrations of CC was quantitatively analyzed using Origin software. Figure 7 The quantitative results.

[0096] Depend on Figure 7 It can be seen that as the concentration of CC increases, the intensity of red color gradually decreases, indicating that the intracellular lipid droplet content is negatively correlated with the concentration of CC.

[0097] 6. 3T3 cells were seeded in 6-well plates and cultured at 37 °C in a cell culture incubator containing 5% CO2 for 12 h. Cells were then treated differently: Blank group – no treatment; SA group – SA gel added only; SACC group – 10 μg / mL curcumin + berberine, followed by differentiation culture. After the adipogenesis induction experiment, total RNA was extracted using a total RNA extraction kit and reverse transcribed into cDNA for subsequent amplification. PCR reaction was prepared using cDNA and SYBR Green qPCR Mix for amplification. 2 −ΔΔCt The method calculates relative gene expression changes compared to the Blank group. Changes in various lipid-related cytokines are obtained. Figure 8 .

[0098] The amplification reaction system contained 10 μL of SYBR Green qPCR Master Mix, 0.4 μL of each forward and reverse primer (10 μM), 2 μL of cDNA, and dd H2O without RNase / DNase to bring the total to 20 μL.

[0099] Depend on Figure 8 It was found that, compared with the untreated group and the gel-only treatment group, the RNA expression levels of cytokines UCP-1, PGC-1α, PRDM16, PPARγ, and AMPK increased in cells treated with soluble acupoint microneedles. The RNA expression levels of cytokines Adipsin and Resistin decreased, indicating the transformation of white adipocytes into brown adipocytes and enhanced lipid metabolism, thus achieving a fat-reducing effect.

[0100] 7. One-month-old SPF-grade male C57BL / 6J mice were used as animal models and divided into 6 groups of 4 mice each: A) normal mouse group (negative group), B) obese model group (positive group), and C) soluble acupoint microneedle patch group (experimental group). Before each treatment, representative mice from each group were photographed. Figure 9 and Figure 10 .

[0101] Depend on Figure 9 and Figure 10 It can be seen that, compared with the normal group of mice, the body length of other groups of mice ( Figure 9 ) and body width ( Figure 10 The results showed that the obese mouse model was successfully established, with the number of mice exceeding that of the normal group.

[0102] 8. Figure 9 The mice used were treated for 4 weeks, then euthanized by cervical dislocation. After dissection, white adipose tissue was collected from each mouse for measurement and photography to obtain... Figure 11 .

[0103] Depend on Figure 11 It can be seen that although the adipose tissue of the experimental group mice has not yet recovered to the level of healthy mice, the fat of the mice is significantly reduced compared with that of the model group, indicating that the treatment of soluble acupoint microneedle patch can alleviate obesity.

[0104] The experimental results above demonstrate that this invention successfully constructed a microneedle carrier using active components of traditional Chinese medicine as structural units. The microneedles successfully penetrate the skin for drug release without causing significant inflammatory reactions. When applied to an obese mouse model, it exhibited a significant weight-loss effect. This integrated drug-carrier tool composed of traditional Chinese medicine components provides a novel strategy for minimally invasive weight loss, minimizing side effects, and improving patient compliance.

[0105] The soluble microneedles provided by this invention are composed entirely of traditional Chinese medicine ingredients and do not require other cross-linking agents as carriers. This achieves the goal of integrating the carrier and drug ingredients, enabling transdermal drug delivery and allowing the entire product to act as a drug on cells after dissolving at acupoints in the body, thus greatly improving the bioavailability of traditional Chinese medicine components.

[0106] It should be noted that when numerical ranges are involved in this invention, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. To avoid redundancy, this invention describes preferred embodiments.

[0107] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments, all of which fall within the scope of the invention.

Claims

1. A soluble microneedle acupoint patch based on a self-carrier of traditional Chinese medicine ingredients, characterized in that, It includes a base layer and a microneedle array composed of microneedles, with a soluble polymer matrix added between the two as a connecting layer; The base layer is made of sodium alginate and puerarin, and the sodium alginate and puerarin are mixed in a mass ratio of 2:5 to form the base layer. The microneedles comprise active components of traditional Chinese medicine, which are made from the following raw materials in parts by weight: Curcumin extract 2 to 6 parts, puerarin extract 30 to 80 parts and berberine extract 2 to 6 parts; The soluble polymer matrix is ​​sodium alginate, and the concentration of sodium alginate is 18 mg / mL to 22 mg / mL, with a molecular weight of 198.

11.

2. The soluble microneedle acupoint patch based on a self-carrier of traditional Chinese medicine components according to claim 1, characterized in that, The active components of the traditional Chinese medicine are made from the following raw materials in parts by weight: 3 to 5 parts curcumin extract, 40 to 60 parts puerarin extract and 3 to 5 parts berberine extract.

3. The soluble microneedle acupoint patch based on a self-carrier of traditional Chinese medicine components according to claim 2, characterized in that, The active components of the traditional Chinese medicine are made from the following raw materials in parts by weight: Four parts of curcumin extract, 50 parts of puerarin extract, and four parts of berberine extract.

4. The soluble microneedle acupoint patch based on a self-carrier of traditional Chinese medicine components according to claim 1, characterized in that, The preparation method of the curcumin extract includes the following steps: The curcumin was dissolved in an extraction solvent and extracted using ultrasound-assisted dissolution to obtain the curcumin extract. The mass ratio of curcumin to the volume ratio of the extraction solvent is 1 mg to 3 mg: 1 mL.

5. A soluble microneedle acupoint patch based on a self-carrier of traditional Chinese medicine components according to claim 1, characterized in that, The preparation method of the berberine extract includes the following steps: Berberine was dissolved in an extraction solvent and extracted using ultrasound-assisted dissolution to obtain the berberine extract. The mass ratio of berberine to the volume ratio of the extraction solvent is 1 mg to 3 mg: 1 mL.

6. A soluble microneedle acupoint patch based on a self-carrier of traditional Chinese medicine components according to any one of claims 4 to 5, characterized in that, The extraction solvent is a mixed solution of ethanol and water in a volume ratio of 1:

1.

7. A soluble microneedle acupoint patch based on a self-carrier of traditional Chinese medicine components according to claim 1, characterized in that, The preparation method of the puerarin extract includes the following steps: Puerarin was dissolved in water, heated to aid dissolution, and extracted to obtain the puerarin extract. The mass ratio of puerarin to water is 40 mg to 60 mg: 1 mL; The heating temperature for aiding dissolution is 99°C to 101°C.

8. The preparation method of the soluble microneedle acupoint patch according to claim 1, characterized in that, Includes the following steps: The curcumin extract and the berberine extract were respectively added to the puerarin extract to obtain a mixed solution; the mass ratio of the curcumin extract, the berberine extract and the puerarin extract was 1~3:1~3:50 respectively. Subsequently, sodium alginate was added to the mixed solution, the temperature was maintained at 90°C~120°C, and after reacting for 15min~10min, it was cooled to 42°C~50°C, transferred to a mold, the mold was placed in a vacuum environment for drying, demolded, and a microneedle array was constructed to obtain the soluble microneedle acupoint patch. The mass ratio of sodium alginate to the volume ratio of the mixed solution is 10 mg to 30 mg: 3 mL.

9. The application of the soluble microneedle acupoint patch according to claim 1 in the preparation of products for treating obesity.

10. The application according to claim 9, characterized in that, The product for treating obesity also includes pharmaceutically acceptable excipients.

Images