Hydrogel patch for promoting blood circulation to remove meridian obstruction and preparation method thereof

Abstract

The invention discloses a hydrogel patch for promoting blood circulation to remove meridian obstruction and a preparation method thereof. The formula of the hydrogel patch for promoting blood circulation to remove meridian obstruction comprises a traditional Chinese medicine concentrated solution for promoting blood circulation to remove meridian obstruction, an oil-in-water emulsion for promoting blood circulation to remove meridian obstruction, sodium polyacrylate, polyacrylic acid, glycerol, azone, dihydroxyaluminum aminoacetate, tartaric acid, disodium ethylene diamine tetraacetate, methylparaben and deionized water. The traditional Chinese medicine concentrated solution for promoting blood circulation to remove meridian obstruction is 70% ethanol extract of vinegar-processed rhizoma corydalis, ligusticum wallichii, philippine flemingia root, safflower, frankincense, myrrh, radix angelicae and liquorice; the oil-in-water emulsion capable of promoting blood circulation to remove meridian obstruction is prepared from a vinegar rhizoma corydalis sesame oil extract, wintergreen oil, methyl glucose sesquistearate, stearate, cetostearyl alcohol, polydimethylsiloxane and deionized water; the blood-activating collateral-dredging hydrogel patch has no skin irritation, belongs to weak sensitization, and has the function of assisting in relieving pain.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical preparations, and particularly relates to a Huoxue Tongluo hydrogel patch and a preparation method thereof. Background Art

[0002] The prescription of the Huoxue Tongluo hydrogel patch consists of nine herbs, namely Corydalis Yanhusuo processed with vinegar, Ligusticum Chuanxiong, Flemingia philippinensis Merr. ex Rolfe, Carthamus tinctorius L., Olibanum, Myrrha, Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f. ex Franch. et Sav., Glycyrrhiza uralensis Fisch., and wintergreen oil. It has the effects of soothing the tendons and activating collaterals, reducing swelling and alleviating pain, and can be used to assist in relieving pain. Its prescription is derived from the experience formula of Wang's Orthopedics in Hebei, and has good clinical efficacy. However, the original dosage form is a black plaster, and the defects of the black plaster are poor patient compliance and high heavy metal contents such as lead and mercury.

[0003] As a new type of external dosage form, hydrogel patches have advantages such as comfort and low skin irritation compared with other traditional external plasters such as rubber plasters, ointments, black plasters, and tinctures. However, at present, traditional Chinese medicine hydrogel patches generally still have problems such as poor adhesiveness and difficulty in adding medicinal oils and traditional Chinese medicine concentrated solutions.

[0004] The adhesion performance affects the effectiveness and comfort of the hydrogel patch. For example, if the adhesive force is too small, the patch is likely to fall off and cannot achieve the therapeutic effect. If the adhesive force is too large, it is difficult to peel off on the skin, or there is a wire drawing phenomenon and it adheres to the clothes. Therefore, it is particularly important for the hydrogel patch to have an appropriate adhesive force.

[0005] Developing the experience formula of Wang's Orthopedics in Hebei into a hydrogel patch with strong patient compliance, good viscosity, comfortable application, and stable addition of medicinal oil and traditional Chinese medicine concentrated solution is an urgent problem to be solved clinically. Summary of the Invention

[0006] The purpose of the present invention is to provide a Huoxue Tongluo hydrogel patch and a preparation method thereof. The Huoxue Tongluo hydrogel patch provided by the present invention has good patient compliance, moderate viscosity, comfortable application, and can stably add medicinal oil and traditional Chinese medicine concentrated solution. To achieve the above purpose, the specific technical solutions of the present invention are as follows:

[0007] First aspect, preparation of traditional Chinese medicine extract

[0008] 2 / 3 of the prescription amount of Corydalis Yanhusuo processed with vinegar, and the prescription amounts of Ligusticum Chuanxiong, Flemingia philippinensis Merr. ex Rolfe, Carthamus tinctorius L., Olibanum, Myrrha, Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f. ex Franch. et Sav., and Glycyrrhiza uralensis Fisch. are reflux-extracted with 70% ethanol to obtain a traditional Chinese medicine concentrated solution for standby;

[0009] 1 / 3 of the prescription amount of Corydalis Yanhusuo processed with vinegar is extracted with sesame oil to obtain a Corydalis Yanhusuo sesame oil extract for standby.

[0010] Second aspect, study on the preparation method of the hydrogel patch

[0011] Five preparation methods of oil-in-water emulsions and hydrogel colloids were studied. Through the appearance and initial adhesion force test results, the optimal preparation method of the oil-in-water emulsion was screened out as follows: 6% of the sesame oil extract of Corydalis yanhusuo, 5% of wintergreen oil, 3% of PEG-20 methyl glucoside sesquistearate, 1% of PEG-100 stearate, 4% of cetearyl alcohol, 1% of polydimethylsiloxane, 80% of deionized water. Mix them, heat up to 80°C - 85°C, homogenize at high speed for 15 - 30 min, rotate at 3000 s / min, and mix evenly to obtain the oil-in-water emulsion. The optimal preparation method of the hydrogel colloid was screened out as follows: 15% of the concentrated traditional Chinese medicine solution, 5% of the oil-in-water emulsion, 6% of sodium polyacrylate, 2% of polyacrylic acid, 20% of glycerol, 0.5% of azone, 0.15% of glycollate aluminum, 0.2% of tartaric acid, 0.1% of disodium ethylenediaminetetraacetate, 0.2% of methylparaben, 50.85% of deionized water. Mix them at a temperature of 18°C - 40°C, stir intermittently for 15 - 30 min to prepare the hydrogel colloid.

[0012] Coat, shape, die-cut, cut, inner package and outer package the obtained hydrogel colloid to obtain the gel patch.

[0013] Thirdly, evaluate the pharmacology, toxicology and pain relief function of the optimal hydrogel patch determined in the second aspect.

[0014] Pharmacology and toxicology results of the hydrogel patch: The acute percutaneous toxicity of rats is slightly toxic; there is no skin irritation; and it has weak sensitization.

[0015] Evaluation results of the pain relief function of the hydrogel patch: It has the function of assisting in relieving pain.

[0016] The beneficial effects of the developed Huoxue Tongluo hydrogel patch in this application are as follows:

[0017] 1. Moderate viscosity;

[0018] 2. The medicinal oil and the concentrated traditional Chinese medicine solution can be stably added;

[0019] 3. Slightly toxic, no skin irritation and weak sensitization;

[0020] 4. It has the function of assisting in relieving pain. Description of the Drawings

[0021] Figure 1 Schematic diagram for the determination of initial adhesion force;

[0022] Figure 2 The rolling distance is 10 mm, and the length of the adhesive surface is 100 mm. Detailed Description of the Invention

[0023] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art.

[0024] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0025] All materials, reagents, etc. in the following examples, unless otherwise specified, can be obtained from commercial sources.

[0026] Reagents and Materials

[0027]

[0028]

[0029] Example 1. Preparation of Chinese herbal medicine extract 1. Chinese herbal medicine feeding prescription (10000 g hydrogel)

[0030]

[0031]

[0032] 2. Preparation method

[0033] Crush 2 / 3 of the amount of vinegar Corydalis, the amount of Chuanxiong, Rhizoma Coptidis, Carthamus, Olibanum, Myrrha, Angelica Dahurica and Radix Glycyrrhizae, add 10 times the amount of 70% ethanol, soak for more than 12h, extract twice with heating and reflux at 70℃, each time for 1h, filter, merge the secondary filtrates, recycle ethanol at 80℃ and concentrate to a density of 1.2g / ml (measured at 80℃), and obtain 1500g of Chinese medicine concentrate for promoting blood circulation and unblocking collaterals for standby use;

[0034] 1500g of the concentrated Chinese medicine for promoting blood circulation and unblocking collaterals is equivalent to 400g of vinegar Corydalis, 300g of Chuanxiong, 300g of Qianjinba, 100g of safflower, 200g of frankincense, 200g of myrrh, 200g of angelica, and 100g of liquorice;

[0035] Crush 1 / 3 of the prescription, i.e. 200g of vinegar Corydalis, add 200g of sesame oil, soak for 12h, slowly heat to 150-170℃, extract for 10-20min, not less than 100℃, filter with 100-mesh silk cloth, remove the drug residue, and obtain the drug oil, i.e. 30g of vinegar Corydalis sesame oil extract for later use;

[0036] Every 30g of vinegar Corydalis sesame oil extract is equivalent to 200g of vinegar Corydalis.

[0037] Example 2: Preparation of a hydrogel patch for promoting blood circulation and unblocking meridians

[0038] 1. Preparation of blood-activating and collateral-draining oil-in-water emulsion

[0039] Weigh 30 g of the sesame oil extract of Corydalis yanhusuo, 25 g of wintergreen oil, 15 g of PEG-20 methyl glucoside sesquistearate, 5 g of PEG-100 stearate, 20 g of cetearyl alcohol, 5 g of polydimethylsiloxane, and 400 g of deionized water respectively, mix them, heat up to 80 °C - 85 °C, and homogenize at high speed for 15 - 30 min at 3000 s / min. After mixing evenly, 500 g of the oil-in-water emulsion for promoting blood circulation and dredging collaterals is obtained for standby;

[0040] The formula of the oil-in-water emulsion for promoting blood circulation and dredging collaterals is converted according to weight percentage: 6% of the sesame oil extract of Corydalis yanhusuo, 5% of wintergreen oil, 3% of PEG-20 methyl glucoside sesquistearate, 1% of PEG-100 stearate, 4% of cetearyl alcohol, 1% of polydimethylsiloxane, and 80% of deionized water;

[0041] Every 500 g of the oil-in-water emulsion for promoting blood circulation and dredging collaterals is equivalent to 200 g of Corydalis yanhusuo and 25 g of wintergreen oil.

[0042] 2. Preparation of the hydrogel colloid for promoting blood circulation and dredging collaterals

[0043] Weigh 150 g of the concentrated traditional Chinese medicine liquid for promoting blood circulation and dredging collaterals, 50 g of the oil-in-water emulsion for promoting blood circulation and dredging collaterals, 60 g of sodium polyacrylate, 20 g of polyacrylic acid, 200 g of glycerol, 5 g of azone, 1.5 g of glyceryl aluminum hydroxide, 2 g of tartaric acid, 1 g of disodium ethylenediaminetetraacetate, 2 g of methylparaben, and 508.5 g of deionized water respectively; mix them at a temperature of 18 °C - 40 °C and stir intermittently for 15 - 30 min to prepare 1000 g of the hydrogel colloid for promoting blood circulation and dredging collaterals;

[0044] The formula of the hydrogel colloid for promoting blood circulation and dredging collaterals is converted according to weight percentage: 15% of the concentrated traditional Chinese medicine liquid for promoting blood circulation and dredging collaterals, 5% of the oil-in-water emulsion for promoting blood circulation and dredging collaterals, 6% of sodium polyacrylate, 2% of polyacrylic acid, 20% of glycerol, 0.5% of azone, 0.15% of glyceryl aluminum hydroxide, 0.2% of tartaric acid, 0.1% of disodium ethylenediaminetetraacetate, 0.2% of methylparaben, and 50.85% of deionized water;

[0045] 1000 g of the hydrogel colloid for promoting blood circulation and dredging collaterals is equivalent to 60 g of Corydalis yanhusuo, 30 g of Ligusticum chuanxiong, 30 g of Flemingia philippinensis, 10 g of Carthamus tinctorius, 20 g of Olibanum, 20 g of Myrrha, 20 g of Angelica dahurica, 10 g of Glycyrrhiza uralensis, and 2.5 g of wintergreen oil;

[0046] 3. Preparation of the hydrogel patch for promoting blood circulation and dredging collaterals

[0047] The hydrogel patch includes a backing layer, a gel layer, and a release paper layer which are stacked in sequence; the gel layer is the above-mentioned hydrogel colloid. The obtained hydrogel colloid is coated, shaped, die-cut, cut, inner-packed, and outer-packed to obtain the hydrogel patch.

[0048] Preparation of Hydrogel Patches of Comparative Examples 1-4

[0049] 1. Preparation of Oil-in-Water Emulsion for Promoting Blood Circulation and Removing Meridian Blockage

[0050] 1.1 Preparation Method

[0051] Refer to "1. Preparation of Oil-in-Water Emulsion for Promoting Blood Circulation and Removing Meridian Blockage" in Example 2, with the difference only in the dosage of excipients. The dosage of excipients is shown in Table 1.

[0052] Table 1. Raw and auxiliary material ratios of oil-in-water emulsions in Comparative Examples 1-4 and Example 1

[0053]

[0054] 1.2 Appearance of Oil-in-Water Emulsion for Promoting Blood Circulation and Removing Meridian Blockage

[0055] Comparative Example 1: The oil-in-water emulsion was not successful. The result of the heat and cold experiment was oil-water separation, indicating insufficient emulsification and insufficient emulsifier. The amount of emulsifier needs to be increased.

[0056] Example 1: The oil-in-water emulsion was successful. The result of the heat and cold experiment was good, without the phenomenon of oil-water separation, and the emulsification was sufficient;

[0057] Comparative Examples 2-4: The oil-in-water emulsion was successful. The result of the heat and cold experiment was good, without the phenomenon of oil-water separation, and the emulsification was sufficient. Although the emulsification was successful in 4 and 5, the amount of emulsifier was relatively large and could be appropriately reduced.

[0058] 2. Preparation of Hydrogel Colloid for Promoting Blood Circulation and Removing Meridian Blockage

[0059] 2.1 Preparation Method

[0060] Refer to "2. Preparation of Hydrogel Colloid for Promoting Blood Circulation and Removing Meridian Blockage" in Example 2, with the difference only in the dosage of raw and auxiliary materials. The dosage of raw and auxiliary materials is shown in Table 2.

[0061] Table 2. Raw and auxiliary material ratios of hydrogel colloids in Comparative Examples 1-4 and Example 1

[0062] Comparative Example 1 Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Traditional Chinese medicine concentrated liquid for activating blood circulation and dredging collaterals (g) 100 150 200 150 200 Oil-in-water emulsion (g) 30 50 70 50 70 Sodium polyacrylate (g) 50 60 70 60 70 Polyacrylic acid (g) 20 20 20 10 10 Glycerol (g) 100 200 200 200 200 Azone (g) 5 5 5 5 5 Glycol aluminum (g) 1.5 1.5 1.6 1.5 1.6 Tartaric acid (g) 2 2 2.5 2 2.5 Disodium ethylenediaminetetraacetate (g) 1 1 1 1 1 Methyl paraben (g) 2 2 2 2 2 Deionized water (g) 688.5 508.5 427.9 518.5 437.9

[0063] 2.2 Appearance of Hydrogel Colloid for Promoting Blood Circulation and Removing Meridian Blockage

[0064] Comparative Example 1: The hydrogel colloid was too soft and too dilute, with a tendency to flow, the appearance was incomplete, the adhesion was strong, but there was a small amount of wire drawing after adhesion;

[0065] Example 1: The hydrogel colloid was of moderate hardness; the gel had a good appearance, strong adhesion, no obvious wire drawing, good elasticity, fineness and good ductility of the colloid;

[0066] Comparative Example 2-4: The hydrogel colloid is slightly hard, dry, has low adhesion, excessive elasticity, and low ductility.

[0067] 3. Preparation of the Blood Activating and Collateral-Promoting Gel Patch

[0068] 3.1 Preparation method

[0069] Refer to "3. Preparation of blood-activating and collateral-draining gel patch" in Example 2.

[0070] 3.2 Appearance of Huoxuetongluo Hydrogel Patch

[0071] Comparative Example 1: The gel of the gel patch is thin, has a tendency to flow, has irregular edges, an incomplete appearance, has strong adhesion, but there will be a small amount of drawing after adhesion, and the backing cloth will absorb liquid and be damp. The gel patch is not ideal;

[0072] Example: 1: Good appearance, strong adhesion, no obvious drawing phenomenon, no slag after curing;

[0073] Comparative Example 2: Good appearance, strong adhesion, no obvious drawing phenomenon, no glue falling off after curing, but slightly weaker adhesion;

[0074] Comparative Example 3: Good appearance, insufficient adhesion, no obvious wire drawing, no glue falling off after curing, but low adhesion;

[0075] Comparative Example 4: The appearance is not ideal, the colloid is hard, there is no obvious wire drawing phenomenon, the adhesion is insufficient, and the residue falls off after curing.

[0076] Test example 1: Initial adhesion test

[0077] 1. Methods

[0078] The inclined ball method is used to test the initial adhesion of the sample by measuring the adhesion of the steel ball to the adhesive surface of the adhesive tape sample when the steel ball and the adhesive surface of the adhesive tape sample are in short contact with each other under weak pressure. Figure 1 shown.

[0079] According to the determination method of initial adhesion (first method) under the general rule 0952 of the fourth volume of the 2020 edition of the Chinese Pharmacopoeia and the national standard GB / T4852-2002

[0080] During the operation, the ball will stay on the paste for a short time after sliding, which will not be counted. The length of sliding is counted as the pause. It is divided into two groups, each with ten pieces, one is the group with high dose of Chinese herbal medicine and the other is the group with low dose, with a thickness of 2mm and non-woven fabric attached on the back.

[0081] Two different doses of gel patches were placed at the same temperature of (23±1)°C and humidity of 60%. Gel patch samples were fixed on the slide of the tackiness tester. The pharmacopoeia method was selected with reference to GB / T4852, the distance of the assisting rolling section was 10 mm, the length of the sample adhesive surface was 100 mm, and the width was 70 mm. As Figure 2 shown, the inspection devices and conditions were the same. Each condition was tested 3 times, and the counts were averaged. Among them, when slipping occurred 2 times under one condition, the count was 100 mm. The averages of the two groups were calculated and compared as the final result.

[0082] 2. Results

[0083] The initial tack of Comparative Example 1 was the largest; the initial tack of Example 1 and Comparative Example 2 was in the middle; the initial tack of Comparative Example 4 was the smallest.

[0084] Note: The thinner the colloid, the greater the adhesive force. The initial tack represents the distance where the ball stops sliding. Those with a large initial tack have jams, while those with a small initial tack do not have jams and will roll down directly.

[0085] Table 3. Initial tack test results of examples and comparative examples

[0086] Sample Initial adhesion force (mm) Whether it gets stuck Comparative Example 1 51 Yes Example 1 62 Yes Comparative Example 2 64 Yes Comparative Example 3 69 No Comparative Example 4 87 No

[0087] 3. Conclusions

[0088] Taking into account the initial tack test results and the appearance of the gel patches, the hydrogel patch of Example 1 has good initial tack and good shape, without obvious wire drawing phenomenon, and does not shed slag after curing. It is the best solution; the hydrogel patch of Example 1 was selected for subsequent pharmacology, toxicology and pharmacodynamics evaluation tests.

[0089] Detection Example 2. Acute percutaneous toxicity test

[0090] 1. Method

[0091] Ten rats were taken, with 5 males and 5 females. The back was depilated, and the depilated area was 40 cm 2 (5 cm×8 cm). After 24 hours, the hydrogel patch of Example 1 was applied to the skin of the back of the rats in the contaminated area at a dose of 5000 mg / kg BW, fixed with non-irritating adhesive tape, and raised individually in a cage for 24 hours. After 24 hours, it was removed from the back of the rats, and the contaminated area was washed with warm water. The general condition, poisoning signs and death of the animals were observed. The observation period was 7 days. The animals were weighed on the 3rd and 7th days respectively. After 7 days, the animals were anesthetized and sacrificed, and anatomical examinations were performed to observe the changes in the heart, liver, spleen, lungs, kidneys and the skin in the contaminated area.

[0092] 2. Results

[0093] During the observation period, no abnormal reactions were observed in the rats, no signs of poisoning appeared, no deaths occurred, and the body weights showed a normal growth trend. After the observation period ended, there were no obvious abnormalities in the hearts, livers, spleens, lungs, kidneys of the rats and the skin in the dosed area. The LD50 of the test animals was greater than 5000 mg / kg BW, and the results are shown in Table 4.

[0094] Table 4. Results of Acute Percutaneous Test

[0095]

[0096] 3. Conclusion

[0097] According to the toxicity classification of Jilin local standard DB 22 / T 396.2-2017, the acute percutaneous toxicity of the hydrogel patch of Example 1 in rats was slightly toxic.

[0098] Test Example 3. Skin Chronic Irritation Test

[0099] 1. Method

[0100] Four rabbits were taken, and the hair on both sides of the spine was removed, and the hair removal area was 3 cm × 3 cm on each side. After 24 hours, 0.5 g of the hydrogel patch of Example 1 was directly applied to the left skin and fixed with non-irritating adhesive tape for 1 hour. The right skin was used as a control, and physiological saline was applied at a dose of 0.5 mL / rabbit. It was applied once a day for 14 consecutive days. Starting from the second day, the hair should be cut before each application, and the skin in the application area should be rinsed with warm water. After 1 hour, the skin reaction at the test site was observed, scored according to the scoring standard of Jilin local standard DB22 / T 396.2-2017, the average score of each animal per day was calculated, and then the skin irritation intensity was judged according to the skin irritation intensity classification standard.

[0101] 2. Results

[0102] The average score of each animal per day < 0.5, and the results are shown in Table 5.

[0103] Table 5. Results of Skin Irritation Test

[0104]

[0105]

[0106] 3. Conclusion

[0107] The gel patch of Example 1 was subjected to a skin chronic irritation test at a dose of 0.5 g / rabbit. According to the skin irritation intensity classification of Jilin local standard DB 22 / T 396.2-2017, it was determined that the hydrogel patch of Example 1 had no skin irritation.

[0108] Test Example 4. Skin Allergy Test

[0109] 1. Method

[0110] 1.1 Hair removal and grouping

[0111] Thirty guinea pigs were taken, and the hair on both sides of the spine on the back was removed. The hair removal area was 6 cm on each side (2 cm × 3 cm). After 24 hours, they were randomly divided into 2 groups according to body weight. There were 10 guinea pigs in the negative control group and 20 guinea pigs in the test substance group, with an equal number of males and females in each group. 2 (2 cm × 3 cm). After 24 hours, they were randomly divided into 2 groups according to body weight. There were 10 guinea pigs in the negative control group and 20 guinea pigs in the test substance group, with an equal number of males and females in each group.

[0112] 1.2 Sensitization contact

[0113] Take 0.2 g of the test substance (the hydrogel patch of Example 1) and apply it to the skin of the left depilated area on the back of the guinea pigs in the test substance group, and then fix it with non-irritating adhesive tape for 6 hours; apply 0.2 mL / guinea pig of normal saline to the left depilated area of the guinea pigs in the negative control group, cover it with two layers of gauze and one layer of sulfuric acid paper, and then fix it with non-irritating adhesive tape for 6 hours. On the 7th day and the 14th day, repeat once in the same way.

[0114] 1.3 Challenge contact

[0115] Fourteen days after the last sensitization with the test substance, apply 0.2 g / guinea pig of the test substance to the right depilated area on the back of the guinea pigs in the test substance group and the control group. The remaining methods are the same as "1.2 Sensitization contact".

[0116] 1.4 Observation

[0117] Observe the skin reaction conditions at 24 hours and 48 hours after challenge contact respectively.

[0118] 2. Results

[0119] At 24 hours and 48 hours after challenge contact, no allergic reactions with an integral ≥ 2 occurred in the right skin of the guinea pigs in the test substance group. The results are shown in Table 6.

[0120] Table 6. Results of skin allergy test

[0121]

[0122] Note: No positive control was set in this test. The results of the positive control test refer to the skin allergy test on March 16, 2023 (performed once every six months according to the test basis).

[0123] 3. Conclusion

[0124] The gel patch of Example 1 was used to conduct a skin allergy test on guinea pigs at a dose of 0.2 g / guinea pig. According to the allergic reaction sensitization intensity classification of Jilin Provincial Local Standard DB 22 / T 396.2 - 2017, it was determined that the hydrogel patch of Example 1 was of weak sensitization.

[0125] Test Example 5. Evaluation of analgesic pharmacodynamics

[0126] 1. Method

[0127] Using the mouse writhing method, 30 mice were selected, and the abdominal hair was removed with a hair removal area of 2.5 cm × 2.5 cm. The mice were randomly divided into 3 groups, namely the blank control group, the positive control group, and the test substance group (the hydrogel patch of Example 1), with 10 mice in each group. 24 hours after hair removal, each mouse in the blank control group was intraperitoneally injected with 0.6% acetic acid at a dose of 0.1 mL / 10 g BW, and the number of writhing times of each mouse within 15 minutes after administration of the pain-inducing agent was recorded with a counter; the test substance was applied to the abdominal hair removal area of the mice in the test substance group at a dose of 0.5 g / rat, and then fixed with non-irritating adhesive tape; the positive control substance was evenly applied to the abdominal hair removal area of the mice at the same dose as the test substance, covered with two layers of gauze and one layer of sulfuric acid paper, and then fixed with non-irritating adhesive tape. After 30 minutes, the covering materials were removed respectively, and acetic acid was injected according to the method of the blank control group and the number of writhing times of the mice was recorded.

[0128] 2. Results

[0129] The number of writhing times of the mice in the test substance group within 15 minutes was significantly less than that of the blank control group, with a significant difference (P < 0.05), and the results are shown in Table 7.

[0130] Table 7. Results of mouse writhing test

[0131]

[0132] Note: The positive control drug is: Diclofenac Diethylamine Emulgel

[0133] 3. Conclusion

[0134] Using the mouse writhing method, the gel patch of Example 1 was applied to the abdomen of mice at a dose of 0.5 g / rat, and the number of writhing times of the mice was significantly less than that of the blank control group, with a significant difference (P < 0.05); according to the result determination standard of Jilin Provincial Local Standard DB 22 / T 396.2 - 2017, it can be determined that the hydrogel patch of Example 1 has the function of assisting in relieving pain under the test dose conditions.

[0135] Although the present invention has been described in detail above with general descriptions and specific embodiments, based on the present invention, some modifications or improvements can be made, which are obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection of the present invention.

Claims

1. A hydrogel patch for promoting blood circulation and unblocking collaterals, comprising a base layer, a gel layer and a protective layer stacked in sequence, wherein the gel layer is prepared from the following raw materials and auxiliary materials by weight percentage: 15% of Huoxuetongluo Chinese medicine concentrate, 5% of Huoxuetongluo oil-in-water emulsion, 6% of sodium polyacrylate, 2% of polyacrylic acid, 20% of glycerol, 0.5% of azone, 0.15% of aluminum glycolate, 0.2% of tartaric acid, 0.1% of disodium ethylenediaminetetraacetate, 0.2% of methylparaben, and 50.85% of deionized water are mixed at a temperature of 18°C-40°C and stirred intermittently for 15-30 minutes to prepare Huoxuetongluo hydrogel colloid, which is the gel layer; The preparation method of the Chinese medicine concentrated solution for promoting blood circulation and unblocking collaterals is as follows: 4 parts of vinegar Corydalis yanhusuo, 3 parts of Chuanxiong, 3 parts of Cnidium monnieri, 1 part of safflower, 1 part of frankincense, 1 part of myrrh, 2 parts of angelica dahurica, and 1 part of liquorice are weighed respectively, crushed, added with 10 times the amount of 70% ethanol, soaked for more than 12 hours, heated under reflux at 70° C. for extraction twice, each time for 1 hour, filtered, combined the secondary filtrates, recovered ethanol at 80° C. and concentrated to a density of 1.2 g / ml Chinese medicine concentrated solution, and the density is measured at 80° C., so as to obtain 15 parts of the Chinese medicine concentrated solution for promoting blood circulation and unblocking collaterals; The preparation method of the vinegar-corydalis sesame oil extract is as follows: 20 parts of vinegar-corydalis and 20 parts of sesame oil are weighed respectively, soaked for 12 hours, slowly heated to 150° C.-170° C., extracted for 10-20 minutes, and obtained 3 parts of vinegar-corydalis sesame oil extract; The preparation method of the water-in-oil emulsion for promoting blood circulation and unblocking meridians comprises the following steps: weighing, by weight percentage, 6% of vinegar yanhu sesame oil extract, 5% of wintergreen oil, 3% of PEG-20 methyl glucose sesquistearate, 1% of PEG-100 stearate, 4% of cetearyl alcohol, 1% of polydimethylsiloxane, and 80% of deionized water, mixing, heating to 80° C.-85° C., high-speed homogenization for 15-30 minutes, rotating at 3000 s / min, and mixing evenly to obtain the water-in-oil emulsion for promoting blood circulation and unblocking meridians.

2. Use of the blood-activating and collateral-draining hydrogel patch as claimed in claim 1 in the preparation of auxiliary pain relief drugs.

3. The acute percutaneous toxicity of the hydrogel patch for promoting blood circulation and unblocking collaterals as claimed in claim 1 to rats is at the slightly toxic level.

4. A hydrogel patch for promoting blood circulation and unblocking meridians as claimed in claim 1 is subjected to a chronic skin irritation test at a dosage of 0.5 g / piece and is determined to be non-irritating to the skin.

5. The blood-activating and collateral-draining hydrogel patch as claimed in claim 1 is weakly sensitizing in a skin allergy test on guinea pigs at a dose of 0.2 g / pig.

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