Soluble micro-needle acupoint application based on self-carrier of traditional Chinese medicine components as well as preparation method and application thereof

Abstract

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

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine and disease treatment, and specifically relates to a soluble microneedle acupoint application based on a traditional Chinese medicine component self-carrier, and a preparation method and application thereof. Background Art

[0002] Obesity is a chronic metabolic disease caused by excessive accumulation of body fat, which significantly increases the risk of cardiovascular disease, type 2 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 risk of relapse. Rationally developing and utilizing products based on active ingredients from traditional Chinese medicines can address these issues.

[0004] Existing active ingredients from traditional Chinese herbal medicines that can be 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 that improves the bioavailability of these active ingredients is needed. Summary of the Invention

[0005] To address the low bioavailability of traditional Chinese medicine components used in the treatment of obesity in the prior art, the present invention provides a soluble microneedle acupuncture point application patch based on a carrier containing traditional Chinese medicine components, as well as its preparation method and application. To achieve the above objectives, the present invention employs the following technical solutions.

[0006] The present invention provides a soluble microneedle acupuncture point application based on a traditional Chinese medicine component self-carrier, comprising a base layer and a microneedle array composed of microneedles, with a soluble polymer matrix added between the base layer 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 mass.

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

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

[0011] The soluble microneedle acupuncture patch provided by the present invention 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 mainly composed of sodium alginate and puerarin. The covalent bonding of amino and carboxyl groups, π-π stacking, and hydrophobic interactions between the two allow them to cross-link with each other, forming a dense and stable cross-linked structure. The microneedle bodies are rich in puerarin, curcumin, and berberine. Through the intermolecular forces provided by a large number of hydrophobic interactions, π-π stacking, and interconnected sugar chains, a hard, soluble microneedle matrix is ​​formed. Due to the simultaneous presence of puerarin in the microneedle matrix and the base layer, the microneedle bodies and the base layer cross-link with each other to form the final microneedle structure, thereby forming the soluble microneedle acupuncture patch. The soluble microneedles provided by the present invention are entirely composed of traditional Chinese medicine ingredients and do not require other cross-linking agents as carriers. This achieves the goal of integrating the carrier and the drug ingredients, allowing transdermal administration and dissolving in acupuncture points in the body, so that all of them act as drugs on cells, greatly improving the in vivo utilization rate of the traditional Chinese medicine components.

[0012] The use of microneedle arrays as drug delivery vehicles is a commonly used strategy. Microneedles can be pressed to penetrate the skin, and drugs can be directly delivered under minimally invasive conditions, so that they are enriched in acupuncture points, greatly improving bioavailability and acupuncture point enrichment. However, the delivery of Chinese medicine components by microneedles requires the preparation of different microneedles according to the physical and chemical properties of the components, and then drug loading, which increases the complexity of the operation. In addition, for a class of metal microneedles, the needle tip may break and cause inflammation, posing a potential biosafety risk. However, the soluble microneedle acupuncture point application provided by the present invention does not have the above problems, and the microneedles are mainly composed of Chinese medicine components, and there is no need to use additional materials to prepare microneedles, realizing the integration of microneedles and drugs. The preparation steps are simplified and the biosafety risk is reduced.

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

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

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

[0016] 4 parts of curcumin extract, 50 parts of puerarin extract and 4 parts of berberine extract.

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

[0018] The curcumin is dissolved in an extraction solvent, and ultrasonic dissolution is used to extract and obtain the curcumin extract.

[0019] The mass ratio of the 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 comprises the following steps:

[0021] Berberine is dissolved in an extraction solvent, and ultrasonic dissolution is used to extract and obtain the berberine extract.

[0022] The mass ratio of the berberine to the volume 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 comprises the following steps:

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

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

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

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

[0029] The curcumin extract and the berberine extract are 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 is 1 to 3:1 to 3:50.

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

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

[0032] The present invention forms a microneedle array in one step through the interaction of active molecules of traditional Chinese medicine itself, without the need for additional materials as microneedle carriers, greatly simplifying the preparation process and improving biocompatibility and bioavailability.

[0033] The present invention also provides the use of the soluble microneedle acupoint application in preparing a product for treating obesity.

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

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

[0036] 1. The present invention provides a soluble microneedle acupuncture patch based on a self-carrier of traditional Chinese medicine ingredients. The soluble microneedle acupuncture patch provided by the present invention 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 mainly composed of sodium alginate and puerarin, and the covalent bonding of amino and carboxyl groups, π-π stacking and hydrophobic interactions between the two make them cross-linked to form a dense and stable cross-linked structure; the microneedle body is rich in puerarin, curcumin and berberine, and a hard soluble microneedle matrix is ​​formed through the intermolecular forces provided by a large number of hydrophobic interactions, π-π stacking and mutual connection of sugar chains. Due to the simultaneous presence of puerarin in the microneedle matrix and the base layer, the microneedle body and the base layer are cross-linked to form the final microneedle structure, thereby forming the soluble microneedle acupuncture patch. The soluble microneedles provided by the present invention are composed entirely of traditional Chinese medicine ingredients and do not require other cross-linking agents as carriers, thus achieving the goal of integrating the carrier and the drug ingredients. They can be administered transdermally and can act on cells as drugs after dissolving in acupuncture points in the body, greatly improving the in vivo utilization rate of the traditional Chinese medicine components.

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

[0038] 3. The present invention completes the preparation of a traditional Chinese medicine-microneedle integrated carrier and uses it for acupoint drug delivery to achieve obesity inhibition effects on inflammation and browning of white fat. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 Characterization of the gel and microneedle in the present invention; wherein, Figure 1 Figure A is a comparison diagram of gel and sol states, where Figure A1 is the gel state and Figure A2 is the sol state; Figure 1 Figure B is a real picture of the microneedle; Figure 1 Figure C is a scanning electron microscope image of the microneedle; Figure 1 Figure D is a magnified scanning electron microscope image.

[0040] Figure 2 The results show that the microneedles containing different concentrations of drugs in the present invention can downregulate pro-inflammatory factors (TNF-α, IL-1β) and upregulate anti-inflammatory factors (IL-10). Figure 2Panel A shows the detection of pro-inflammatory factor TNF-α; Figure 2 Panel B shows the detection of pro-inflammatory factor IL-1β; Figure 2 Figure C shows the detection of the anti-inflammatory factor IL-10.

[0041] Figure 3 This is an H&E slice of the skin after the composite microneedle penetrates the skin.

[0042] Figure 4 Schematic diagram of the browning of white cell fat under the intervention of drugs in the present invention.

[0043] Figure 5 This is a fluorescence image of the drug uptake by 3T3 cells in the present invention that changes over time; wherein, Figure 5 Figure A is a bright field image of cells; Figure 5 Panel B in the figure shows the fluorescence imaging of the drug; Figure 5 Figure C in the figure is the imaging of the cell nucleus; Figure 5 Figure D in the figure is Figure 5 Figure B and Figure 5 Overlay image of panel C in .

[0044] Figure 6 is the change in lipid droplet content before and after microneedle treatment in the present invention; wherein, Figure 6 Figure A is before treatment; Figure 6 Figure B is after processing.

[0045] Figure 7 This is the trend of the fat accumulation amount of the cells in the present invention changing with the drug concentration.

[0046] Figure 8 is the change in the expression level of obesity-related cytokines in the present invention; wherein, Figure 8 Panel A shows the mRNA expression level of UCP-1; Figure 8 Panel B shows the mRNA expression level of PGC-1α; Figure 8 Panel C shows the mRNA expression level of PRDM16; Figure 8 Figure D shows the mRNA expression level of PPARγ; Figure 8 Panel E in the figure shows the mRNA expression level of AMPK; Figure 8 Figure F shows the mRNA expression level of Adipsin; Figure 8 Figure G shows the mRNA expression level of Resistin.

[0047] Figure 9 This is a representation of the body length of mice in different treatment groups in the present invention. The six mice from left to right correspond to the normal group, obesity model group, catgut embedment weight loss group, sham catgut embedment group, Western medicine group and microneedle group.

[0048] Figure 10 This is a representation of the body width of mice in different treatment groups in the present invention. The six mice from left to right correspond to the normal group, obesity model group, catgut embedment weight loss group, sham catgut embedment group, Western medicine group and microneedle group.

[0049] Figure 11 Figure 2 is a physical picture of the adipose tissue of mice in different treatment groups in the present invention; wherein, Figure 11 Figure A shows the adipose tissue of normal mice; Figure 11 Figure B shows the adipose tissue of drug-induced obesity model mice; Figure 11 Figure C shows the adipose tissue of mice after treatment with soluble microneedle acupoint application; the four samples from left to right correspond to the adipose tissue of four mice in each group as parallel controls. DETAILED DESCRIPTION

[0050] The present invention will be described in detail below with reference to the accompanying drawings and specific examples, but they should not be construed as limiting the present invention. Unless otherwise specified, the technical means used in the following examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources.

[0051] Example 1: Preparation and structural characterization of soluble microneedle acupoint application based on traditional Chinese medicine component self-carrier I. Preparation of soluble microneedle acupoint application based on traditional Chinese medicine component self-carrier

[0052] 1. Dissolve 2 mg of curcumin in 1 mL of extraction solvent and use ultrasonic dissolution to obtain solution A, i.e., curcumin extract.

[0053] The concentration of curcumin in solution A is 2 mg / mL.

[0054] The ultrasonic dissolution time was 10 min and the temperature was maintained at 25°C.

[0055] The extraction solvent was a mixed solution of ethanol and ultrapure water in a volume ratio of 1:1.

[0056] Curcumin is a powdered solid purchased from Aladdin Chemical Reagent Network (CAS: 458-37-7, molecular weight: 368.38, molecular formula: C 21 H 20 O6).

[0057] 2. Dissolve 2 mg of berberine in 1 mL of extraction solvent and use ultrasonic dissolution to obtain solution B, i.e., berberine extract.

[0058] The concentration of berberine in solution B is 2 mg / mL.

[0059] The ultrasonic dissolution time was 10 min and the temperature was maintained at 25°C.

[0060] The extraction solvent was a mixed solution of ethanol and ultrapure water in a volume ratio of 1:1.

[0061] Berberine is a powdered solid purchased from Aladdin Chemical Reagent Network (CAS: 2086-83-1, molecular weight: 336.37, molecular formula: C 20 H 18 NO4).

[0062] 3. Dissolve 50 mg of puerarin in 3 mL of ultrapure water and heat to aid dissolution to obtain solution C, i.e., puerarin extract.

[0063] The concentration of puerarin in solution C was 16.7 mg / mL.

[0064] Puerarin is a powdered solid purchased from Aladdin Chemical Reagent Network (CAS: 3681-99-0, molecular weight: 416.38, molecular formula: C 21 H 20 O9).

[0065] The temperature for heating and dissolving was maintained at 100°C in an oil bath environment.

[0066] The heating dissolution time was 10 min, and stirring was slow.

[0067] 4. Add 100 μL of solution A and 100 μL of solution B dropwise to solution C, followed by adding 20 mg of sodium alginate to obtain an amorphous gel.

[0068] The temperature of solution C was maintained at 100°C.

[0069] 5. After the amorphous gel is reacted for 10 minutes, a mixture D is obtained, and the mixture D is transferred to a mold. The mold is placed in a vacuum environment for drying, and demolded to construct a microneedle array to obtain a soluble microneedle acupuncture point application.

[0070] The mixture D was cooled to 45° C. after the reaction.

[0071] The volume of the above mixture D in the mold was 400 μL.

[0072] The mold is a 10×10 conical array.

[0073] Each microneedle in the mold has a length of 600 μm and a bottom diameter of 300 μm.

[0074] It should be noted that the mixture D was demoulded after being kept in a vacuum environment for 40 minutes.

[0075] 2. Structural Characterization of Soluble Microneedle Acupoint Application Based on Traditional Chinese Medicine Self-Carrier

[0076] 1. Add 1 mL of mixture D to a 10 mL flat-bottom glass bottle and cool to room temperature. Then take a photo. Figure 1 As shown in Figure A1 in Figure A.

[0077] 2. Maintain the mixture D at 45℃ to turn it into sol state and observe Figure 1 Figure A2 in Figure A.

[0078] 3. At 100°C, add 400 μL of mixture D to the microneedle mold. The mold is a 10 cm × 10 cm conical array. Each microneedle in the mold is 600 μm long and has a bottom diameter of 300 μm. Place the mold in a vacuum environment for 40 minutes, then demold and take pictures to obtain Figure 1 Figure B in .

[0079] 4. Microneedle SEM imaging, SEM model is JSM-6390LV, magnification is 65 (, electron beam energy is 5keV, obtain Figure 1 Figure C in the figure is enlarged 180 degrees (photographed later) Figure 1 Figure D in .

[0080] Example 2: Efficacy evaluation of soluble microneedle acupoint application based on traditional Chinese medicine component self-carrier

[0081] 1. 2×10 4 The mouse macrophage cell line RAW264.7 was inoculated into a six-well culture plate at a density of cells / mL and cultured for 24 hours. In each six-well culture plate, only complete culture medium was added as a negative control group, only lipopolysaccharide (LPS: 200ng / μL) was added as a positive control group, and LPS and different SA (sodium alginate) material patches (SA material control group, 5μg / mL, 10μg / mL and 25μg / mL CC (curcumin + berberine)) were added as experimental groups. The plates were then co-cultured for another 24 hours. 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 (Biyuntian Biological Reagent Co., Ltd.) to obtain Figure 2 Figure A in Figure 2 Figure B and Figure 2 Figure C in .

[0082] Among them, the mouse macrophage cell line RAW264.7 was sourced from Wuhan Punosai Life Science Technology Co., Ltd.

[0083] The source / formula composition of the complete culture medium is Wuhan Punosai Life Science Technology Co., Ltd., and the main components include fetal bovine serum, L-glutamine, HEPES buffer, sodium bicarbonate, and penicillin-streptomycin.

[0084] CC is the drug component in soluble microneedle acupoint patching. Therefore, when validating the inflammatory regulation efficacy of soluble microneedle acupoint patching at the cellular level, its active ingredients were selected for study. The results showed that compared with the untreated group (negative group), the LPS-treated group (positive group) showed an increase in the level of proinflammatory factors (IL-10) and a decrease in the levels of anti-inflammatory factors (TNF-α and IL-1). Compared with the positive group, the levels of proinflammatory factors decreased and anti-inflammatory factors increased in the CC-treated groups at different concentrations. As CC concentration increased, the decrease in proinflammatory factors increased, while the increase in anti-inflammatory factors increased. The results showed that CC treatment at different concentrations promoted the expression of anti-inflammatory factors and inhibited the expression of proinflammatory factors (TNF-α and IL-1) to a certain extent; CC concentration was positively correlated with the change in the amount of anti-inflammatory factors and negatively correlated with the change in the amount of proinflammatory factors.

[0085] 2. Take a one-month-old SPF male C57BL / 6J mouse, remove the hair on the back, and press the soluble acupoint microneedle on the depilated area. After 1 minute, remove the microneedle, cut the corresponding skin, and immediately immerse and fix the tissue in 4% paraformaldehyde for 24 hours. Perform H&E staining, and observe under a normal light microscope to obtain Figure 3 .

[0086] Among them, one-month-old SPF male C57BL / 6J mice were sourced from Beijing Weitonglihua Experimental Animal Technology Co., Ltd.

[0087] 3. 3T3 cells were seeded on confocal microplates and cultured in a cell culture incubator at 37°C with 5% CO2 for 12 hours. Serum-free culture medium containing 10 μg / mL curcumin and berberine was added to the microplates. Changes in intracellular fluorescence were observed under a microscope at 6 hours, 12 hours, and 24 hours to determine the time-dependent changes in cellular uptake of drug molecules. Figure 5 .

[0088] Among them, the source of 3T3 cells is Wuhan Punosai Life Science Technology Co., Ltd.

[0089] The source / formulation of serum-free culture medium for curcumin and berberine was obtained from Wuhan Punosai Life Science Technology Co., Ltd.

[0090] The drug was labeled with red fluorescence, and the cell nucleus was labeled with blue fluorescence for cell localization. As can be seen from the figure, the red fluorescence intensity in the cells gradually increased with time, indicating that the CC uptake of 3T3 cells was positively correlated with the culture time.

[0091] 4. 3T3 cells were seeded into two confocal microplates respectively and cultured in a cell culture incubator at 37°C with 5% CO2 for 12 hours. Serum-free culture medium containing 10 μg / mL curcumin and berberine was added to the microplates. After culturing for 12 hours, the cells were induced to adipogenically. The complete adipogenic differentiation culture medium in the microplate was aspirated and rinsed twice with 1×PBS. A 4% neutral formaldehyde solution was added to cover the cell surface and the cells were fixed for 30 minutes. During the cell fixation period, Oil Red O working solution was prepared (saturated Oil Red O solution: pure water = 3:2, mixed and filtered with neutral filter paper to remove impurities). The 4% neutral formaldehyde solution was aspirated and rinsed twice with 1×PBS. 1 mL of Oil Red O working solution was added to each dish and stained at room temperature for 30 minutes. The Oil Red O working solution was aspirated and rinsed twice with 1×PBS to wash away background impurities. The images were observed and photographed under a laser scanning confocal microscope to obtain the images. Figure 6 .

[0092] Among them, saturated red oil O dye solution (10 mL) was purchased from Wuhan Punosai Life Science Technology Co., Ltd.

[0093] As can be seen from the figure, after the cells were treated with CC, the red signal in the cells was significantly reduced, indicating that CC treatment can effectively reduce the intracellular lipid droplet content.

[0094] 5. Origin software was used to quantitatively analyze the red color intensity in cells after treatment with different concentrations of CC. Figure 7 quantified results.

[0095] Depend on Figure 7 It can be seen that as the CC concentration increases, the red color intensity gradually decreases, indicating that the intracellular lipid droplet content is negatively correlated with the CC concentration.

[0096] 6. 3T3 cells were seeded in 6-well plates and cultured in a cell culture incubator at 37°C with 5% CO2 for 12 hours. The cells were then treated in different ways: Blank group - no treatment; SA group - only SA gel was added; SACC group - 10 μg / mL curcumin + berberine, and then cultured for differentiation. After the adipogenic induction experiment was completed, total RNA was extracted using a total RNA extraction kit. It was then reverse transcribed into cDNA for subsequent amplification. PCR reaction system was prepared using cDNA and SYBR Green qPCR Mix for amplification. 2 -ΔΔCt Methods The relative gene expression changes compared with the Blank group were calculated. The changes of each fat-related cytokine were obtained. Figure 8 .

[0097] The amplification reaction system contained 10 μL SYBR Green qPCR Master Mix, 0.4 μL of each forward primer and reverse primer (10 μM), 2 μL cDNA, and RNase / DNase-free dd H2O to 20 μL.

[0098] Depend on Figure 8 Compared to the untreated and gel-only treated groups, the RNA expression levels of the cytokines UCP-1, PGC-1α, PRDM16, PPARγ, and AMPK increased in cells treated with soluble acupoint microneedle application. The RNA expression levels of the cytokines Adipsin and Resistin decreased, indicating a transition from white adipocytes to brown adipocytes, enhanced lipid metabolism, and a fat-reducing effect.

[0099] 7. One-month-old SPF male C57BL / 6J mice were used as model animals and divided into 6 groups, 4 mice in each group, namely A normal mouse group (negative group), B obesity model group (positive group), C soluble acupoint microneedle application group (experimental group). Before different treatments, the representative mice of each group were photographed. Figure 9 and Figure 10 .

[0100] Depend on Figure 9 and Figure 10 It can be seen that compared with the normal group of mice, the body length of mice in other groups ( Figure 9 ) and body width ( Figure 10 ) was greater than that of the normal group, indicating that the obese mouse model was successfully established.

[0101] 8. Figure 9 After 4 weeks of treatment, the mice were euthanized by cervical dislocation. After autopsy, the white adipose tissue of each mouse was obtained, and the size was measured and photographed. Figure 11 .

[0102] 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 the model group, indicating that soluble acupoint microneedle application treatment can alleviate obesity.

[0103] The above experimental results demonstrate that the present invention has successfully constructed a microneedle carrier based on active components of traditional Chinese medicine. The microneedles can successfully penetrate the skin to release the drug without causing significant inflammatory reactions. When applied to an obese mouse model, they demonstrated significant weight loss. This integrated drug-carrier tool, comprised of traditional Chinese medicine components, offers a novel strategy for minimally invasive weight loss, minimizing side effects, and improving patient compliance.

[0104] The soluble microneedles provided by the present invention are composed entirely of traditional Chinese medicine ingredients and do not require other cross-linking agents as carriers, thus achieving the goal of integrating the carrier and the drug ingredients. They can be administered transdermally and can act on cells as drugs after dissolving in acupuncture points in the body, greatly improving the in vivo utilization rate of the traditional Chinese medicine components.

[0105] It should be noted that when the present invention involves a numerical range, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. To avoid redundancy, the present invention describes a preferred embodiment.

[0106] Although preferred embodiments of the present invention have been described, those skilled in the art may make additional changes and modifications to these embodiments once the basic inventive concepts become known, and all such changes and modifications fall within the scope of the present invention.

Claims

1. A soluble microneedle acupuncture point application based on a traditional Chinese medicine component self-carrier, characterized in that: The microneedle array comprises a base layer and microneedles, with a soluble polymer matrix added between the base layer and the microneedle array as a connecting layer. 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. The microneedles include active components of traditional Chinese medicine, which are made of the following raw materials in parts by weight: 2 to 6 parts of curcumin extract, 30 to 80 parts of puerarin extract, and 2 to 6 parts of berberine extract; The soluble polymer matrix is ​​sodium alginate, the concentration of the sodium alginate is 18 mg / mL to 22 mg / mL, and the molecular weight is 198.

11.

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

3. The soluble microneedle acupuncture point application based on a traditional Chinese medicine component self-carrier according to claim 2, characterized in that: The active ingredients of traditional Chinese medicine are prepared from the following raw materials in parts by weight: 4 parts of curcumin extract, 50 parts of puerarin extract and 4 parts of berberine extract.

4. The soluble microneedle acupuncture point application based on a traditional Chinese medicine component self-carrier according to claim 1, characterized in that: The preparation method of the curcumin extract comprises the following steps: Dissolving the curcumin in an extraction solvent, and extracting to obtain the curcumin extract using ultrasonic dissolution assistance; The mass ratio of the curcumin to the volume ratio of the extraction solvent is 1 mg to 3 mg: 1 mL.

5. The soluble microneedle acupuncture point application based on a traditional Chinese medicine component self-carrier according to claim 1, characterized in that: The preparation method of the berberine extract comprises the following steps: dissolving berberine in an extraction solvent, and extracting to obtain the berberine extract using ultrasonic dissolution assistance; The mass ratio of the berberine to the volume of the extraction solvent is 1 mg to 3 mg: 1 mL.

6. A soluble microneedle acupuncture point application based on a traditional Chinese medicine component self-carrier 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. The soluble microneedle acupuncture point application based on a traditional Chinese medicine component self-carrier according to claim 1, characterized in that: The preparation method of the puerarin extract comprises the following steps: dissolving puerarin in water, heating to aid dissolution, and extracting to obtain the puerarin extract; The mass ratio of the puerarin to the volume of the water is 40 mg to 60 mg: 1 mL; The temperature of the heating dissolution-aid is 99°C to 101°C.

8. The method for preparing the soluble microneedle acupoint application according to claim 1, characterized in that: The steps include: adding the curcumin extract and the berberine extract to the puerarin extract respectively to obtain a mixed solution; the mass ratio of the curcumin extract, the berberine extract and the puerarin extract is 1-3:1-3:50; Subsequently, the sodium alginate is added to the mixed solution, the temperature is maintained at 90°C to 120°C, the reaction is carried out for 15min to 10min, the mixture is cooled to 42°C to 50°C, the mixture is transferred to a mold, the mold is placed in a vacuum environment for drying, and the mold is demoulded to construct a microneedle array to obtain the soluble microneedle acupuncture point application; The mass ratio of the sodium alginate to the volume of the mixed solution is 10 mg to 30 mg: 3 mL.

9. Use of the soluble microneedle acupoint application patch according to claim 1 in preparing a product for treating obesity.

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

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