Controlled-release Chinese herbal medicine blood-activating and pain-relieving patch and preparation method thereof

Abstract

The application belongs to the technical field of traditional Chinese medicine preparation, and particularly relates to a controlled-release Chinese herbal medicine blood-activating and pain-relieving patch and a preparation method thereof. The controlled-release Chinese herbal medicine blood-activating and pain-relieving patch is composed of the following components in percentage by mass: modified hyaluronic acid 2-10%, blood-activating and pain-relieving traditional Chinese medicine extract 15-20%, azone 0.3-0.5%, polyvinyl alcohol 1-5%, tartaric acid 0.1-0.3%, sodium dodecyl sulfonate 0.3-0.5%, yellow angelica alcohol 0.5-1%, glycerol 25-35%, glycoxy aluminum 0.1-0.3%, and the balance of distilled water. The Chinese herbal medicine blood-activating and pain-relieving patch has good controlled release and pain-relieving effects, good peeling performance and adhesion, and obviously improves the mechanical properties and use experience of the pain-relieving patch.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, and in particular relates to a controlled-release herbal blood-activating and pain-relieving patch and its preparation method. Background Technology

[0002] The Blood-Activating and Pain-Relieving Plaster is made from more than 20 medicinal herbs, including peony bark, pepper, and cloves. It is a common external medicine with analgesic, anti-inflammatory, and blood-activating properties, and has long played an important role in relieving joint pain and promoting blood circulation. Traditionally, the Blood-Activating and Pain-Relieving Plaster is made with a rubber base, but rubber bases have problems such as strong skin irritation, organic solvent residue, and difficulty in controlling the drug release rate. Therefore, it is necessary to modify its dosage form to improve the therapeutic effect and user experience.

[0003] In recent years, with the development of materials science and formulation technology, gel ointments have gradually emerged as a new dosage form for blood-activating and analgesic ointments. Gel ointments, using water-soluble polymers as a matrix, offer better skin compatibility and breathability, reducing skin irritation and allergic reactions. Simultaneously, the controlled-release properties of gel ointments allow for more uniform and sustained drug release, thereby improving therapeutic efficacy. However, gel ointments still suffer from poor adhesion and peeling properties during use. Furthermore, the lipophilic components in blood-activating and analgesic ointments exhibit poor integration with the hydrogel matrix. Therefore, formulation improvements are urgently needed to address these issues. Summary of the Invention

[0004] In order to overcome the shortcomings of the prior art, one of the objectives of this invention is to provide a controlled-release herbal blood-activating and pain-relieving patch. This pain-relieving patch not only has good controlled-release and pain-relieving effects, but also has good peeling performance and adhesion, which significantly improves the mechanical properties and user experience of the pain-relieving patch.

[0005] The second objective of this invention is to provide a method for preparing a controlled-release traditional Chinese medicine blood-activating and pain-relieving patch.

[0006] One of the objectives of this invention is achieved through the following technical solution: A controlled-release herbal blood-activating and pain-relieving patch, comprising the following components by weight percentage: 2-10% modified hyaluronic acid, 15-20% herbal extract for activating blood circulation and relieving pain, 0.3-0.5% azone, 1-5% polyvinyl alcohol, 0.1-0.3% tartaric acid, 0.3-0.5% sodium dodecyl sulfonate, 0.5-1% yellow angelicol, 25-35% glycerin, 0.1-0.3% aluminum hydroxyacetate, with the balance being distilled water.

[0007] Furthermore, the preparation method of the modified hyaluronic acid is as follows: (1) Dissolve hyaluronic acid in water, adjust the pH with hydrochloric acid, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide and stir until homogeneous, then add 3-aminophenylboronic acid and stir to react; the reaction solution is dialyzed and freeze-dried to obtain pretreated hyaluronic acid; (2) Sodium periodate was added to the pretreated hyaluronic acid aqueous solution to carry out the reaction in the dark, and ethylene glycol was added to terminate the reaction. The reaction solution was dialyzed and freeze-dried to obtain the intermediate product. (3) The intermediate product was added to an acetate buffer solution, and sodium chlorite was added to carry out the reaction in the dark. The pH was adjusted to 8-8.5 with sodium hydroxide solution to terminate the reaction. The reaction solution was dialyzed and freeze-dried to obtain modified hyaluronic acid.

[0008] Further, in step (1), the mass ratio of hyaluronic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide and 3-aminophenylboronic acid is 1:(2-3):(1-2):(0.4-0.6).

[0009] Further, in step (1), the pH is adjusted to 5.5-6.5; the stirring reaction time is 5-7 hours.

[0010] Further, in step (2), the mass ratio of the pretreated hyaluronic acid to sodium periodate is 1:1.5-2.5.

[0011] Furthermore, in step (2), the light-avoidance reaction time is 1-3 hours.

[0012] Further, in step (3), the mass ratio of the intermediate product to sodium chlorite is 1:1.5-2.5; and the pH of the acetate buffer solution is 4.5.

[0013] Furthermore, in step (3), the light-protected reaction time is 18-24 hours.

[0014] Furthermore, the preparation method of the blood-activating and pain-relieving traditional Chinese medicine extract is as follows: Weigh out 5-10 parts by weight of pepper, 8-10 parts of cloves, 2-6 parts of peony bark, 10-15 parts of angelica root, 5-10 parts of cinnamon twig, 2-6 parts of chuanxiong rhizome, 2-6 parts of chili pepper, 5-10 parts of achyranthes root, and 5-10 parts of safflower, grind them into powder, add 6-10 times the amount of 90% ethanol and soak for 2-4 days, percolate, collect the percolate, concentrate it to a relative density of 1.20-1.28, add 5-10 parts of menthol and 5-10 parts of borneol, stir evenly to obtain a traditional Chinese medicine extract for promoting blood circulation and relieving pain.

[0015] The second objective of this invention is achieved by the following technical solution: The preparation method of the above-mentioned controlled-release traditional Chinese medicine blood-activating and pain-relieving patch includes the following steps: a. Add aluminum hydroxyl, sodium dodecyl sulfate, and yellow angelic alcohol to glycerol according to the specified ratio, and stir to mix evenly to obtain phase A; b. Add modified hyaluronic acid, blood-activating and pain-relieving traditional Chinese medicine extract, azone, tartaric acid and polyvinyl alcohol to water, stir and mix thoroughly to obtain phase B; c. Mix phase B and phase A, stir thoroughly, apply to nonwoven fabric and cure to obtain the final product.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) This invention provides a controlled-release herbal blood-activating and pain-relieving patch, which uses modified hyaluronic acid as a gel matrix and is combined with ingredients such as yellow angelica alcohol and aluminum hydroxide, which effectively improves the drug controlled-release capability of the gel patch. Specifically, the modified hyaluronic acid of this invention forms a cross-linking network with aluminum hydroxide through carboxylic acid groups, and at the same time forms a hydrogen bond network with yellow angelica alcohol, constructing a multi-network structure, which effectively limits the diffusion rate of drug molecules, thereby achieving the drug controlled-release effect; at the same time, the dynamic borate ester bond formed by the phenylboronic acid group in the modified hyaluronic acid and polyvinyl alcohol further enhances the drug controlled-release stability of the pain relief patch; in addition, the modified hyaluronic acid introduces aromatic rings and carbon chains by forming hydrogen bonds with yellow angelica alcohol, which improves the lipophilicity of the pain relief patch matrix, so that the herbal extract can better enter the pain relief patch matrix, which helps to improve the transdermal penetration capability of the drug.

[0017] (2) The crosslinking of the carboxylic acid group of the modified hyaluronic acid of the present invention with aluminum hydroxyl can enhance the cohesive force of the gel, thereby improving the peeling performance of the gel patch; while the carboxylic acid group that does not participate in the crosslinking can enhance the adhesion of the gel patch. The synergistic effect of the two improves the mechanical properties and user experience of the pain relief patch.

[0018] (3) This invention provides a method for preparing a controlled-release herbal blood-activating and pain-relieving patch. The method is simple and efficient. Furthermore, the multi-network structure design in this invention achieves synergistic optimization of drug controlled release and physical properties, providing a new strategy for the development of pain-relieving patches. Attached Figure Description

[0019] Figure 1 These are the infrared spectra of hyaluronic acid before and after modification according to the present invention. Detailed Implementation

[0020] The present invention will now be further described with reference to the accompanying drawings and specific embodiments. It should be noted that, without conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments. Specific conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, all reagents or instruments used are conventional products obtained through commercial channels.

[0021] Example 1 A controlled-release herbal blood-activating and pain-relieving patch is composed of the following ingredients by weight percentage: 6% modified hyaluronic acid, 17% herbal extract for activating blood circulation and relieving pain, 0.4% azone, 3% polyvinyl alcohol, 0.2% tartaric acid, 0.4% sodium dodecyl sulfonate (SDS), 0.75% yellow angelic alcohol, 30% glycerin, 0.2% aluminum hydroxyacetate, and the balance being distilled water.

[0022] The modified hyaluronic acid is prepared as follows: (1) Hyaluronic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC), N-hydroxysuccinimide (NHS) and 3-aminophenylboronic acid were weighed in a mass ratio of 1:2.5:1.5:0.5. Hyaluronic acid was dissolved in deionized water, and the pH was adjusted to 6.0 with 1M hydrochloric acid solution. EDC and NHS were added and stirred evenly. Then 3-aminophenylboronic acid was added and reacted for 6 hours. The reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 6 kDa and dialyzed with deionized water for 7 days. The dialyzed product was freeze-dried to obtain pretreated hyaluronic acid. (2) Take pretreated hyaluronic acid, sodium periodate and ethylene glycol according to the ratio of 1g:2g:4mL respectively. Dissolve the pretreated hyaluronic acid in deionized water, then add sodium periodate and react in the dark for 2 hours. Add ethylene glycol to terminate the reaction, then transfer the reaction solution to a dialysis bag with a molecular weight cutoff of 6kDa, dialyze with deionized water for 7 days, freeze dry to obtain the intermediate product. (3) Weigh the intermediate product and sodium chlorite in a mass ratio of 1:2. Add the intermediate product to an acetate buffer solution with a pH of 4.5 (composed of 0.045M sodium acetate solution and 0.055M acetic acid solution). Add sodium chlorite and react fully in the dark for 20 hours. Adjust the pH of the system to 8.2 with 5M sodium hydroxide solution to terminate the reaction. Then transfer the reaction solution to a dialysis bag with a molecular weight cutoff of 6kDa, dialyze with deionized water for 7 days, and freeze dry to obtain modified hyaluronic acid.

[0023] The preparation method of the blood-activating and pain-relieving herbal extract is as follows: By weight, weigh 8 parts of pepper, 8 parts of cloves, 4 parts of peony bark, 12 parts of angelica dahurica, 7 parts of cinnamon twig, 4 parts of chuanxiong rhizome, 4 parts of chili pepper, 7 parts of achyranthes bidentata, and 8 parts of safflower, grind them into powder, add 8 times the amount of 90% ethanol and soak for 3 days, percolate, collect the percolate, concentrate it to a relative density of 1.25, add 8 parts of menthol and 8 parts of borneol, stir evenly, and obtain a traditional Chinese medicine extract for promoting blood circulation and relieving pain.

[0024] This embodiment also provides a method for preparing the above-mentioned controlled-release traditional Chinese medicine blood-activating and pain-relieving patch, including the following steps: a. Add aluminum hydroxyl, SDS and yellow angelicol to glycerol according to the specified ratio, stir and mix evenly to obtain phase A; b. Add modified hyaluronic acid, blood-activating and pain-relieving traditional Chinese medicine extract, azone, tartaric acid and polyvinyl alcohol to water, stir and mix thoroughly to obtain phase B; c. Mix phase B and phase A, stir thoroughly, apply to nonwoven fabric and cure to obtain the final product.

[0025] Example 2 A controlled-release herbal blood-activating and pain-relieving patch is composed of the following ingredients by weight percentage: 2% modified hyaluronic acid, 15% herbal extract for activating blood circulation and relieving pain, 0.3% azone, 1% polyvinyl alcohol, 0.1% tartaric acid, 0.3% SDS, 0.5% yellow angelicol, 25% glycerin, 0.1% aluminum hydroxyacetate, and the balance being distilled water.

[0026] The modified hyaluronic acid is prepared as follows: (1) Hyaluronic acid, EDC, NHS and 3-aminophenylboronic acid were weighed according to the mass ratio of 1:2:1:0.4. Hyaluronic acid was dissolved in deionized water and the pH was adjusted to 5.5 with 1M hydrochloric acid solution. EDC and NHS were added and stirred evenly. Then 3-aminophenylboronic acid was added and reacted for 5 hours. The reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 5 kDa and dialyzed with deionized water for 8 days. The dialysis product was freeze-dried to obtain pretreated hyaluronic acid. (2) Take pretreated hyaluronic acid, sodium periodate and ethylene glycol according to the ratio of 1g:1.5g:2mL respectively. Dissolve the pretreated hyaluronic acid in deionized water, add sodium periodate and react in the dark for 1 hour, then add ethylene glycol to terminate the reaction; then transfer the reaction solution to a dialysis bag with a molecular weight cutoff of 5kDa, dialyze with deionized water for 8 days, freeze dry to obtain the intermediate product; (3) Weigh the intermediate product and sodium chlorite in a mass ratio of 1:1.5. Add the intermediate product to an acetate buffer solution with a pH of 4.5 (composed of 0.045M sodium acetate solution and 0.055M acetic acid solution). Add sodium chlorite and react fully in the dark for 18 hours. Adjust the pH of the system to 8.0 with 5M sodium hydroxide solution to terminate the reaction. Then transfer the reaction solution to a dialysis bag with a molecular weight cutoff of 5kDa, dialyze with deionized water for 8 days, and freeze dry to obtain modified hyaluronic acid.

[0027] The preparation method of the blood-activating and pain-relieving herbal extract is as follows: Weigh out 5 parts by weight of pepper, 5 parts of cloves, 2 parts of peony bark, 10 parts of angelica root, 5 parts of cinnamon twig, 2 parts of chuanxiong rhizome, 2 parts of chili pepper, 5 parts of achyranthes root, and 5 parts of safflower. Crush them and add 6 times the amount of 90% ethanol to soak for 4 days. Percolate, collect the percolate, concentrate it to a relative density of 1.20, add 5 parts of menthol and 5 parts of borneol, stir well, and obtain a traditional Chinese medicine extract for promoting blood circulation and relieving pain.

[0028] This embodiment also provides a method for preparing the above-mentioned controlled-release traditional Chinese medicine blood-activating and pain-relieving patch, including the following steps: a. Add aluminum hydroxyl, SDS and yellow angelicol to glycerol according to the specified ratio, stir and mix evenly to obtain phase A; b. Add modified hyaluronic acid, blood-activating and pain-relieving traditional Chinese medicine extract, azone, tartaric acid and polyvinyl alcohol to water, stir and mix thoroughly to obtain phase B; c. Mix phase B and phase A, stir thoroughly, apply to nonwoven fabric and cure to obtain the final product.

[0029] Example 3 A controlled-release herbal blood-activating and pain-relieving patch is composed of the following ingredients by weight percentage: 10% modified hyaluronic acid, 20% herbal extract for activating blood circulation and relieving pain, 0.5% azone, 5% polyvinyl alcohol, 0.3% tartaric acid, 0.5% SDS, 1% yellow angelicol, 35% glycerin, 0.3% aluminum hydroxyl, and the balance being distilled water.

[0030] The modified hyaluronic acid is prepared as follows: (1) Hyaluronic acid, EDC, NHS and 3-aminophenylboronic acid were weighed according to the mass ratio of 1:3:2:0.6. Hyaluronic acid was dissolved in deionized water, and the pH was adjusted to 6.5 with 1M hydrochloric acid solution. EDC and NHS were added and stirred evenly. Then 3-aminophenylboronic acid was added and reacted for 7 hours. The reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 8 kDa and dialyzed with deionized water for 5 days. The dialysis product was freeze-dried to obtain pretreated hyaluronic acid. (2) Take pretreated hyaluronic acid, sodium periodate and ethylene glycol according to the ratio of 1g:2.5g:6mL respectively. Dissolve the pretreated hyaluronic acid in deionized water, add sodium periodate and react in the dark for 3 hours. Add ethylene glycol to terminate the reaction. Then transfer the reaction solution to a dialysis bag with a molecular weight cutoff of 8kDa, dialyze with deionized water for 5 days, freeze dry to obtain the intermediate product. (3) Weigh the intermediate product and sodium chlorite in a mass ratio of 1:2.5. Add the intermediate product to an acetate buffer solution (composed of 0.045M sodium acetate solution and 0.055M acetic acid solution) with a pH of 4.5. Add sodium chlorite and react fully in the dark for 24 hours. Adjust the pH of the system to 8.5 with 5M sodium hydroxide solution to terminate the reaction. Then transfer the reaction solution to a dialysis bag with a molecular weight cutoff of 8kDa, dialyze with deionized water for 5 days, and freeze dry to obtain modified hyaluronic acid.

[0031] The preparation method of the blood-activating and pain-relieving herbal extract is as follows: By weight, weigh 10 parts of pepper, 10 parts of cloves, 6 parts of peony bark, 15 parts of angelica root, 10 parts of cinnamon twig, 6 parts of chuanxiong rhizome, 6 parts of chili pepper, 10 parts of achyranthes root, and 10 parts of safflower, grind them into powder, add 10 times the amount of 90% ethanol and soak for 4 days, percolate, collect the percolate, concentrate it to a relative density of 1.28, add 10 parts of menthol and 10 parts of borneol, stir evenly, and obtain a traditional Chinese medicine extract for promoting blood circulation and relieving pain.

[0032] This embodiment also provides a method for preparing the above-mentioned controlled-release traditional Chinese medicine blood-activating and pain-relieving patch, including the following steps: a. Add aluminum hydroxyl, SDS and yellow angelicol to glycerol according to the specified ratio, stir and mix evenly to obtain phase A; b. Add modified hyaluronic acid, blood-activating and pain-relieving traditional Chinese medicine extract, azone, tartaric acid and polyvinyl alcohol to water, stir and mix thoroughly to obtain phase B; c. Mix phase B and phase A, stir thoroughly, apply to nonwoven fabric and cure to obtain the final product.

[0033] Comparative Example 1 This Comparative Example 1 is basically the same as Example 1, except that the modified hyaluronic acid is replaced with hyaluronic acid.

[0034] Comparative Example 2 Comparative Example 2 is basically the same as Example 1, except that Comparative Example 2 omits yellow angelicol.

[0035] Experimental Example 1 The modified hyaluronic acid prepared in Example 1 of this invention was subjected to infrared spectroscopy, and the results are as follows: Figure 1 As shown.

[0036] Depend on Figure 1Infrared spectra show that, compared to hyaluronic acid, the infrared spectrum of pretreated hyaluronic acid is in the 1600-1500 cm⁻¹ range. -1 The presence of a characteristic absorption peak for the benzene ring indicates successful grafting of the phenylboronic acid group; compared to pretreated hyaluronic acid, the infrared spectrum of the intermediate product is significantly better in the 1700-1750 cm⁻¹ region. -1 The presence of characteristic peaks for aldehyde groups indicates successful oxidation of the pretreated hyaluronic acid; compared to the intermediate product, the infrared spectrum of the modified hyaluronic acid is significantly better in the 3500-3200 cm⁻¹ range. -1 The significantly enhanced characteristic peak of the carboxyl hydroxyl group indicates that the modified hyaluronic acid was successfully prepared.

[0037] Experimental Example 2 In accordance with the provisions of the General Rules for Adhesion Test of Plasters in Part IV of the 2020 edition of the Chinese Pharmacopoeia, the peel strength of the above-mentioned analgesic patches was tested, and the test results are shown in Table 1.

[0038] Table 1 As shown in Table 1, the peel strength of Examples 1-3 is superior to that of Comparative Examples 1-2. Analysis reveals that the crosslinking of the carboxylic acid groups in the modified hyaluronic acid with aluminum hydroxide enhances the cohesive force of the gel, thereby improving the peel performance of the gel patch; while the uncrosslinked carboxylic acid groups in the modified hyaluronic acid enhance the adhesion of the gel patch. The synergistic effect of both significantly improves the usability and user experience of the gel patch.

[0039] Experimental Example 3 In vitro percutaneous permeation test A Franz-type diffusion cell was used, with an effective diffusion area of ​​3.14 cm². 2 Using mouse abdominal skin as a transdermal barrier, 20 mL of receiving solution (phosphate buffer containing 10 vol% ethanol, pH=7.4) was added to the receiving pool. The analgesic patches obtained in Examples 1-3 and Comparative Examples 1-2 were smoothly applied to the mouse skin surface (stratum corneum). The magnetic stirrer was set to 400 rpm to maintain uniform distribution of components in the receiving solution. Samples of 1 mL of receiving solution were collected at 0.5 h, 4 h, 8 h, 12 h, 18 h, and 24 h, respectively. Fresh receiving solution of the same volume and temperature was added immediately after each sampling to maintain a constant liquid volume and temperature in the receiving pool. The collected samples were centrifuged at 12000 rpm for 5 min to separate the supernatant. The supernatant was filtered through a 0.22 μm filter membrane, and the eugenol content was determined by high-performance liquid chromatography (UPLC). The cumulative release rate of eugenol (L) was calculated. n The results are shown in Table 2.

[0040] Q n W represents the content of eugenol in the receiving pool at the sampling time point, and W represents the content of eugenol in the analgesic patch.

[0041] Table 2 The cumulative release rates of the analgesic patches in Examples 1-3 and Comparative Examples 1-2 are shown in Table 2. Table 2 shows that the release rate of Examples 1-3 is relatively slow, indicating that the analgesic patch of the present invention, using modified hyaluronic acid as the gel matrix and incorporating ingredients such as yellow angelicol and aluminum hydroxyl, effectively improves the drug-controlled release capability of the gel patch. The release effects of Comparative Examples 1-2 are not ideal, indicating that the multiple network structure of the present invention, in conjunction with the lipophilic effect of yellow angelicol, jointly achieves an ideal drug-controlled release effect.

[0042] Test Example 4 First, the temperature of the super-constant temperature water bath was precisely adjusted to 55℃. After the temperature stabilized, the hot plate was preheated at this temperature for 10 minutes to achieve a stable testing environment. Subsequently, SPF-grade healthy ICR mice (weighing 18-22 g) were selected as experimental subjects and acclimatized for 3 days in a standardized animal room at 23±2℃ and (55±5)% relative humidity, with free access to food and water. Each mouse was placed one by one in the center area of ​​the preheated hot plate, and the latency (seconds) from contact with the hot plate to the first licking of the hind paw or jumping (defined as the hind limb completely leaving the hot plate) was closely observed and recorded as the baseline pain threshold. To ensure the accuracy and reliability of the experimental data, mice with a baseline pain threshold <5 s (indicating hyperalgesia) or >30 s (indicating hypoalgesia) were excluded, as were individuals exhibiting jumping escape behavior during the experiment.

[0043] Mice meeting the experimental requirements were randomly divided into four groups: Example 1, Example 2, Example 3, Comparative Example 1, Comparative Example 2, and Blank Control Group, with 10 mice in each group. During the experiment, mice in each experimental group were treated with the analgesic patch prepared according to this invention, while mice in the blank control group were treated with a blank patch of equal area, and the treatment was carried out continuously for 3 days.

[0044] After treatment, i.e., 1 hour after the last administration, the pain threshold of the mice was measured again, and the changes in pain threshold of each group of mice were compared. The results are recorded in Table 3.

[0045] Table 3 Pain threshold typically refers to the minimum stimulus intensity at which an individual can perceive pain. An increased pain threshold indicates a greater tolerance to pain. As shown in Table 3, compared to the blank control group, the pain thresholds of Examples 1-3 were significantly increased, indicating that the analgesic patch of this invention has a good analgesic effect.

[0046] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. A controlled-release traditional Chinese medicine blood-activating and pain-relieving patch, characterized in that, The product is composed of the following ingredients by weight percentage: 2-10% modified hyaluronic acid, 15-20% traditional Chinese medicine extract for promoting blood circulation and relieving pain, 0.3-0.5% azone, 1-5% polyvinyl alcohol, 0.1-0.3% tartaric acid, 0.3-0.5% sodium dodecyl sulfonate, 0.5-1% yellow angelicol, 25-35% glycerin, 0.1-0.3% aluminum hydroxyacetate, and the balance being distilled water.

2. The controlled-release herbal blood-activating and pain-relieving patch according to claim 1, characterized in that, The modified hyaluronic acid is prepared as follows: (1) Dissolve hyaluronic acid in water, adjust the pH with hydrochloric acid, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide and stir until homogeneous, then add 3-aminophenylboronic acid and stir to react; the reaction solution is dialyzed and freeze-dried to obtain pretreated hyaluronic acid; (2) Sodium periodate was added to the pretreated hyaluronic acid aqueous solution to carry out the reaction in the dark, and ethylene glycol was added to terminate the reaction. The reaction solution was dialyzed and freeze-dried to obtain the intermediate product. (3) The intermediate product was added to an acetate buffer solution, and sodium chlorite was added to carry out the reaction in the dark. The pH was adjusted to 8-8.5 with sodium hydroxide solution to terminate the reaction. The reaction solution was dialyzed and freeze-dried to obtain modified hyaluronic acid.

3. The controlled-release herbal blood-activating and pain-relieving patch according to claim 2, characterized in that, In step (1), the mass ratio of hyaluronic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide and 3-aminophenylboronic acid is 1:(2-3):(1-2):(0.4-0.6).

4. The controlled-release herbal blood-activating and pain-relieving patch according to claim 2, characterized in that, In step (1), the pH is adjusted to 5.5-6.5; the stirring reaction time is 5-7 hours.

5. The controlled-release herbal blood-activating and pain-relieving patch according to claim 2, characterized in that, In step (2), the mass ratio of the pretreated hyaluronic acid to sodium periodate is 1:1.5-2.

5.

6. The controlled-release herbal blood-activating and pain-relieving patch according to claim 2, characterized in that, In step (2), the light-avoidance reaction takes 1-3 hours.

7. The controlled-release herbal blood-activating and pain-relieving patch according to claim 2, characterized in that, In step (3), the mass ratio of the intermediate product to sodium chlorite is 1:1.5-2.5; the pH of the acetate buffer solution is 4.

5.

8. The controlled-release herbal blood-activating and pain-relieving patch according to claim 2, characterized in that, In step (3), the light-avoidance reaction takes 18-24 hours.

9. The controlled-release herbal blood-activating and pain-relieving patch according to claim 1, characterized in that, The preparation method of the blood-activating and pain-relieving herbal extract is as follows: Weigh out 5-10 parts by weight of pepper, 8-10 parts of cloves, 2-6 parts of peony bark, 10-15 parts of angelica root, 5-10 parts of cinnamon twig, 2-6 parts of chuanxiong rhizome, 2-6 parts of chili pepper, 5-10 parts of achyranthes root, and 5-10 parts of safflower, grind them into powder, add 6-10 times the amount of 90% ethanol and soak for 2-4 days, percolate, collect the percolate, concentrate it to a relative density of 1.20-1.28, add 5-10 parts of menthol and 5-10 parts of borneol, stir evenly to obtain a traditional Chinese medicine extract for promoting blood circulation and relieving pain.

10. The preparation method of the controlled-release traditional Chinese medicine blood-activating and pain-relieving patch according to any one of claims 1-9, characterized in that, Includes the following steps: a. Add aluminum hydroxyl, sodium dodecyl sulfate, and yellow angelic alcohol to glycerol according to the specified ratio, and stir to mix evenly to obtain phase A; b. Add modified hyaluronic acid, blood-activating and pain-relieving traditional Chinese medicine extract, azone, tartaric acid and polyvinyl alcohol to water, stir and mix thoroughly to obtain phase B; c. Mix phase B and phase A, stir thoroughly, apply to nonwoven fabric and cure to obtain the final product.

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