CN110075169A - A kind of compound percutaneous plaster and preparation method thereof for treating chronic ache - Google Patents

Abstract

The present invention relates to pharmaceutical technology fields, it specifically discloses a kind of for treating the compound percutaneous plaster of chronic ache, is made of the following components according to parts by weight: 1~3 part of 10~20 parts of safflower, 20~35 parts of rhizoma corydalis, 5~8 parts of radix paeoniae rubra, 3~5 parts of lidocaine hydrochloride injection, dipropium dipropionate and betamethasone sodium phosphate mixture, 1~3 part of compound penetrating agent.The present invention also provides a kind of for treating the preparation method of the compound percutaneous plaster of chronic ache.Provided by the present invention for treating the compound percutaneous plaster of chronic ache, there is good therapeutic effect for chronic ache.

Description

A composite transdermal patch for treating chronic pain and its preparation method

technical field

The invention relates to the technical field of medicine, and specifically discloses a composite transdermal patch for treating chronic pain and a preparation method thereof.

Background technique

"Chronic pain" can cause a series of pathophysiological changes from the peripheral to the central nervous system, and show different pathological changes through specific symptoms and signs. Chronic pain is not only frequent and persistent, but also seriously affects the work and life of patients.

The treatment of chronic pain is currently dominated by oral drugs, and nerve block therapy can be performed on the corresponding nerves innervating the pain area to regulate nerve function. At present, the nerve block is mainly punctured with a syringe under the guidance of B-ultrasound. The needle tip of the syringe reaches the corresponding nerve and injects drugs. The commonly used drugs are a mixture of local anesthetics and hormones. Nerve block is a traumatic operation with associated risks. The operation is technically difficult, and it can only be performed in a hospital, so it is not easy to implement on a large scale.

SUMMARY OF THE INVENTION

The invention provides a composite transdermal patch for treating chronic pain. The composite transdermal patch contains relevant components of nerve block medication, and can be applied to the patient's painful area to treat pain. It can be used by itself, safe, effective and convenient to use.

The first object of the present invention is to provide a compound transdermal patch for treating chronic pain, which is made of the following components in parts by weight: 10-20 parts of safflower, 20-35 parts of corydalis, red 5-8 parts of peony root, 3-5 parts of lidocaine hydrochloride injection, 1-3 parts of mixture of betamethasone dipropionate and betamethasone sodium phosphate, 1-3 parts of compound penetration enhancer;

Wherein, the mass ratio of betamethasone dipropionate to betamethasone sodium phosphate is 3-5:2.

Further, a compound transdermal patch for treating chronic pain is made of the following components in parts by weight: 15 parts of safflower, 28 parts of Corydalis Corydalis, 6 parts of Radix Paeoniae Rubra, 5 parts of Lidocaine Hydrochloride Injection 3 parts of betamethasone dipropionate and betamethasone sodium phosphate mixture, 1 part of compound penetration enhancer;

Wherein, the mass ratio of betamethasone dipropionate to betamethasone sodium phosphate is 4:2.

Further, the concentration of lidocaine hydrochloride in the lidocaine hydrochloride injection is 0.1g/5mL.

Further, the compound penetration enhancer is selected from ethanol, propylene glycol, fatty acid ester, dimethyl sulfoxide and its congeners, oleic acid, linoleic acid, lauryl alcohol, azone and its homologues, lauryl One or more of sodium sulfate, Tween-80, urea, salicylic acid, pyrrolidones, menthol, camphor, limonene, and eucalyptol.

Furthermore, the composite penetration enhancer is composed of ethanol, menthol and camphor in a mass ratio of 3:3:4.

The second object of the present invention is to provide a method for preparing a composite transdermal patch for the treatment of chronic pain, specifically according to the following steps:

Step 1. Weigh 10-20 parts of safflower, 20-35 parts of Corydalis Corydalis, 5-8 parts of Radix Paeoniae Rubra, 3-5 parts of lidocaine hydrochloride injection, betamethasone dipropionate and betamethasone dipropionate in parts by weight. 1-3 parts of metasone sodium phosphate mixture, 1-3 parts of compound penetration enhancer;

Wherein, the mass ratio of said betamethasone dipropionate to betamethasone sodium phosphate is 3-5:2;

Step 2, pulverizing the safflower, corydalis, and red peony root weighed in step 1, sieving, and mixing uniformly to obtain a solid powder mixture;

Step 3, mix the lidocaine hydrochloride injection, betamethasone dipropionate and betamethasone sodium phosphate mixture, composite penetration enhancer and step 2 obtained in step 1, and then press its Add 60-80% of the binder by total weight, stir evenly, and degas to obtain the drug mixture;

Step 4. Apply the drug mixture obtained in Step 3 on a release paper, cover with a release-controlling film after drying, cut, seal and package to obtain a composite transdermal patch.

Further, the sieving described in step 2 is through a 200 mesh sieve.

Further, the adhesive is an acrylate copolymer emulsion.

Further, the release-controlling membrane is selected from one of ethylene-vinyl acetate copolymer membranes, polyvinyl chloride membranes, polyethylene membranes or microporous polypropylene membranes.

Furthermore, the controlled-release film is a polyethylene film.

The pharmacological effect of Chinese medicine component in the present invention is as follows:

1, Flos Carthami: pungent, warm, nontoxic. Go into the heart, Liver Channel. It has the effects of promoting blood circulation to stimulate menstruation, dissipating blood stasis and relieving pain. It is used to treat amenorrhea, dysmenorrhea, lochia, chest pain and heartache, stagnant abdominal pain, chest and hypochondrium pain, bruises, sore swelling and pain, etc. Modern pharmacological studies have proved that a small dose of safflower decoction can slightly excite the isolated toad heart and the in vivo heart of a rabbit, making the heart beat powerful and increase the amplitude; large doses have an inhibitory effect on the heart, slowing down the heart rate and contracting the myocardium. Weakened force and reduced cardiac output; safflower can directly or partially antagonize the effect of a-adrenergic receptors to dilate blood vessels, and has a weaker direct vasoconstrictive effect; safflower yellow has a very significant inhibitory effect on ADP Induced platelet aggregation in rabbits, and also has a very obvious depolymerization effect on platelets that have been aggregated by ADP; safflower has obvious analgesic effect; It has obvious inhibitory effect on the increase of rat skin capillary permeability caused by histamine, and has obvious inhibitory effect on the formation of cotton ball granuloma in rats; safflower has obvious immune activity, safflower polysaccharide It can promote the transformation of lymphocytes, increase the number of spleen cells forming plaques on sheep red blood cells, and resist the immunosuppressive effect of prednisolone.

2. Corydalis Corydalis: pungent, bitter, warm, nontoxic. Return liver, stomach, heart, lung, spleen channel. It has the effects of promoting blood circulation and removing blood stasis, regulating qi and relieving pain. It is mainly used for the treatment of confidants' waist and knee pain, irregular menstruation, lump in the abdomen, metrorrhagia, postpartum hemorrhage, lochia, bruises and other diseases. Modern pharmacological experimental studies have proved that Corydalis has a good analgesic effect and can be used for pain relief; processed and extracted with Corydalis to make 0.2% corydaline injection, which can be used for local anesthesia; Corydalis powder has analgesic effect, and its potency is 1% of that of opium. /10, the effect can last for 2 hours; Corydalis alcohol extract can significantly expand the coronal cordal vessels of isolated rabbit heart and cat heart in vivo, reduce coronary resistance and increase blood flow.

3. Radix Paeoniae Rubra: Bitter in the mouth, slightly cold in nature. Return liver channel. It has the functions of clearing away heat and cooling blood, dissipating blood stasis and relieving pain. Raw Radix Paeoniae Rubra has the power to clear away heat and cool blood. It is mostly used for body heat bleeding, red eyes, swelling and pain, carbuncle and sore due to febrile disease and heat entering the blood system. Modern pharmacological experimental studies have proved that the extract of Radix Paeoniae Rubra has significant inhibitory effects on platelet aggregation induced by adrenaline, adenosine diphosphate (ADP), iron head snake venom (TMVA) and arachidonic acid (AA) in vitro. Platelet adhesion and platelet factor 3 activity are reduced, and cAMP content in platelets is increased; Radix Paeoniae Rubra can lower blood fat and resist arteriosclerosis; Radix Radix Radix Radix Paeoniae Rubra can resist thrombosis; Radix Radix Radix Radix Paeoniae Rubra can resist tumor;

Compared with prior art, the beneficial effects of the present invention are:

In the transdermal patch for treating chronic pain provided by the present invention, safflower, corydalis, red peony root, lidocaine hydrochloride injection, betamethasone dipropionate and betamethasone sodium phosphate mixture are used together, wherein red Hua Huoxue stimulates the menstrual flow, dissipates blood stasis and relieves pain, Corydalis Husuo promotes blood circulation and dissipates blood stasis, regulates qi and relieves pain, Chi Shao clears heat and cools blood, dissipates blood stasis and relieves pain, the combination of the three can effectively relieve pain, and the analgesic effect of Corydalis Corydalis lasts for a long time. Corydalis also has a certain anesthetic effect, which can work together with lidocaine hydrochloride to increase the pain threshold of the pain site, and has an analgesic and analgesic effect; safflower, Corydalis, red peony Both have anti-inflammatory effects, and work together with betamethasone dipropionate and betamethasone sodium phosphate mixture to have curative effects on the slow pain caused by various inflammatory lesions; and the transdermal patch provided by the invention can be used during hospitalization It can be used by itself after being discharged from the hospital, and it is safe, effective and convenient to use.

Detailed ways

In order to enable those skilled in the art to better understand that the technical solutions of the present invention can be implemented, the present invention will be further described below in conjunction with specific examples, but the given examples are not intended to limit the present invention.

The mass concentration of lidocaine hydrochloride in lidocaine hydrochloride injection in the following each embodiment and comparative example is 0.1g/5mL, and lidocaine hydrochloride injection, betamethasone dipropionate and betamethasone sodium phosphate come from Prescribed by the hospital and purchased in the hospital.

Example 1

A compound transdermal patch for treating chronic pain, which is made of the following components in parts by weight: 10 parts of safflower, 20 parts of Corydalis Corydalis, 5 parts of Radix Paeoniae Rubra, 3 parts of Lidocaine Hydrochloride Injection, 1 part of mixture of betamethasone dipropionate and betamethasone sodium phosphate, 1 part of compound penetration enhancer;

Wherein, the mass ratio of betamethasone dipropionate to betamethasone sodium phosphate is 3:2;

The composite penetration enhancer is composed of propylene glycol and linoleic acid in a mass ratio of 1:1;

A preparation method for a composite transdermal patch for treating chronic pain, specifically according to the following steps:

Step 1. Weigh 10 parts of safflower, 20 parts of Corydalis Corydalis, 5 parts of Radix Paeoniae Rubra, 3 parts of lidocaine hydrochloride injection, 1 part of betamethasone dipropionate and betamethasone sodium phosphate mixture in parts by weight, compound 1 part of penetration enhancer;

Step 2, pulverizing the safflower, corydalis, and red peony root weighed in step 1, passing through a 200-mesh sieve, and mixing uniformly to obtain a solid powder mixture;

Step 3, mix the lidocaine hydrochloride injection, betamethasone dipropionate and betamethasone sodium phosphate mixture, composite penetration enhancer and step 2 obtained in step 1, and then press its Add 60% acrylate copolymer emulsion by total weight, stir evenly, and degas to obtain a drug mixture;

Step 4. Apply the drug mixture obtained in Step 3 on the anti-adhesive paper, cover the polyvinyl chloride film after drying, cut, seal and pack to obtain the composite transdermal patch.

Example 2

A composite transdermal patch for treating chronic pain, which is made of the following components in parts by weight: 20 parts of safflower, 35 parts of Corydalis Corydalis, 8 parts of Radix Paeoniae Rubra, 5 parts of Lidocaine Hydrochloride Injection, 3 parts of betamethasone dipropionate and betamethasone sodium phosphate mixture, 3 parts of compound penetration enhancer;

Wherein, the ratio by weight of betamethasone dipropionate to betamethasone sodium phosphate is 5:2.

The composite penetration enhancer is composed of ethanol, limonene and Tween-80 in a mass ratio of 1:2:4;

A preparation method for a composite transdermal patch for treating chronic pain, specifically according to the following steps:

Step 1. Weigh 20 parts of safflower, 35 parts of Corydalis Corydalis, 8 parts of Radix Paeoniae Rubra, 5 parts of lidocaine hydrochloride injection, 3 parts of betamethasone dipropionate and betamethasone sodium phosphate mixture in parts by weight, compound 3 parts of penetration enhancer;

Step 2, pulverizing the safflower, corydalis, and red peony root weighed in step 1, passing through a 200-mesh sieve, and mixing uniformly to obtain a solid powder mixture;

Step 3, mix the lidocaine hydrochloride injection, betamethasone dipropionate and betamethasone sodium phosphate mixture, composite penetration enhancer and step 2 obtained in step 1, and then press its Add 80% acrylate copolymer emulsion by total weight, stir evenly, and degas to obtain a drug mixture;

Step 4. Apply the drug mixture obtained in Step 3 on a release paper, cover with ethylene-vinyl acetate copolymer film after drying, cut, seal and package to obtain a composite transdermal patch.

Example 3

A composite transdermal patch for treating chronic pain, which is made of the following components in parts by weight: 15 parts of safflower, 28 parts of Corydalis Corydalis, 6 parts of Radix Paeoniae Rubra, 5 parts of Lidocaine Hydrochloride Injection, 3 parts of mixture of betamethasone dipropionate and betamethasone sodium phosphate, 1 part of compound penetration enhancer;

Wherein, the ratio by weight of betamethasone dipropionate to betamethasone sodium phosphate is 4:2.

The compound penetration enhancer is composed of ethanol, menthol and camphor in a mass ratio of 3:3:4;

A preparation method for a composite transdermal patch for treating chronic pain, specifically according to the following steps:

Step 1. Weigh 15 parts of safflower, 28 parts of Corydalis Corydalis, 6 parts of Radix Paeoniae Rubra, 5 parts of Lidocaine Hydrochloride Injection, 3 parts of betamethasone dipropionate and betamethasone sodium phosphate mixture in parts by weight, compound 1 part of penetration enhancer;

Step 2, pulverizing the safflower, corydalis, and red peony root weighed in step 1, passing through a 200-mesh sieve, and mixing uniformly to obtain a solid powder mixture;

Step 3, mix the lidocaine hydrochloride injection, betamethasone dipropionate and betamethasone sodium phosphate mixture, composite penetration enhancer and step 2 obtained in step 1, and then press its Add 70% acrylate copolymer emulsion by total weight, stir evenly, and degas to obtain a drug mixture;

Step 4. Apply the drug mixture obtained in Step 3 on a release paper, cover with a polyethylene film after drying, cut, seal and package to obtain a composite transdermal patch.

Comparative Example 1

A composite transdermal patch for treating chronic pain, which is made of the following components in parts by weight: 5 parts of lidocaine hydrochloride injection, 3 parts of betamethasone dipropionate and betamethasone sodium phosphate mixture 1 part, 1 part of compound penetration enhancer;

Wherein, the ratio of parts by weight of betamethasone dipropionate to betamethasone sodium phosphate is 4:2;

The compound penetration enhancer is composed of ethanol, menthol and camphor in a mass ratio of 3:3:4;

A preparation method for a composite transdermal patch for treating chronic pain, specifically according to the following steps:

Step 1. Weigh 5 parts of lidocaine hydrochloride injection, 3 parts of betamethasone dipropionate and betamethasone sodium phosphate mixture, and 1 part of composite penetration enhancer in parts by weight;

Step 2. Mix the lidocaine hydrochloride injection, betamethasone dipropionate, betamethasone sodium phosphate mixture and composite penetration enhancer weighed in step 1, and then add 70% acrylate copolymerization agent according to its total weight. The product emulsion was stirred evenly and degassed to obtain a drug mixture;

Step 4. Apply the drug mixture obtained in Step 3 on a release paper, cover with a polyethylene film after drying, cut, seal and package to obtain a composite transdermal patch.

Comparative Example 2

A compound transdermal patch for treating chronic pain, which is made of the following components in parts by weight: 15 parts of safflower, 28 parts of Corydalis Corydalis, 6 parts of Radix Paeoniae Rubra, and 1 part of compound penetration enhancer;

Among them, the composite penetration enhancer is composed of ethanol, menthol and camphor in a mass ratio of 3:3:4;

A preparation method for a composite transdermal patch for treating chronic pain, specifically according to the following steps:

Step 1. Weigh 15 parts of Safflower, 28 parts of Corydalis Corydalis, 6 parts of Radix Paeoniae Rubra, and 1 part of compound penetration enhancer in parts by weight;

Step 2, pulverizing the safflower, corydalis, and red peony root weighed in step 1, passing through a 200-mesh sieve, and mixing uniformly to obtain a solid powder mixture;

Step 3. Mix the compound penetration enhancer weighed in step 1 and the solid powder mixture obtained in step 2 evenly, then add 70% acrylate copolymer emulsion according to its total weight, stir evenly, and degas to obtain a drug mixture ;

Step 4. Apply the drug mixture obtained in Step 3 on a release paper, cover with a polyethylene film after drying, cut, seal and package to obtain a composite transdermal patch.

The effect of the composite transdermal patch for treating chronic pain prepared in each embodiment and comparative example is evaluated below.

1. Acute Toxicity

1. Main reagents

10% chloral hydrate (Qingdao Yulong Seaweed Co., Ltd.);

8% sodium sulfide (Qingdao Yulong Seaweed Co., Ltd.).

2. Experimental animals

120 rats, half male and half male, all provided by Shanghai Slack Experimental Animal Co., Ltd., weighing 180-220 g. Placed in a breeding room with a room temperature of 23 ± 2°C and a relative humidity of 50 ± 10%, which was set to be illuminated for 12 hours a day, the metabolic cage was raised alone, and the commercially available mouse food and water were freely ingested in the food box in the breeding cage.

3. Method

120 rats were divided into complete example 1 group, complete example 2 group, complete example 3 group, complete comparative example 1 group, complete comparative example 2 group, complete blank group and damaged example 1 according to random number table method Group, damaged example group 2, damaged example group 3, damaged comparative example group 1, damaged comparative example group 2, damaged blank group, 10 rats in each group.

Administration method:

a. Hair removal Hair removal was carried out 24 hours before administration. Rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3ml/100g). The hair on the back of the rat was removed along both sides of the spine with a pet shaver (the area is 30 cm ² , about 10% of the body surface area), and then 8% sodium sulfide was used to remove the hair, and the residual hair was completely removed as the standard. Try to avoid damage to the epidermis due to drug overdose;

b. Preparation of damaged skin The damaged skin was prepared after 24 hours of depilation. Use a blunt blade to lightly scrape the depilated skin on the back, so as to ooze blood under the skin without causing damage to the epidermis. The patch prepared by each group was applied externally on the depilated part of the back of the rats. After external application, the metabolic cages were kept separately. After applying medicine 24h, remove drug patch, observe continuously for 14 days, including animal body weight change, diet, appearance, behavior, secretion, excrement, death situation and poisoning reaction (symptom of poisoning reaction, severity, starting time, duration, reversibility, etc.). Dying and dead animals and rats that had been weighed were dissected in time, and the changes in the volume, color, and texture of each organ were observed.

4. Statistical methods

Statistical analysis was performed using SPSS17.0. The mean value of the experimental data is express.

5. Results

5.1 Dead rats

After one administration of the test drug, during the entire observation period, all animals grew normally, coat color, behavioral activities, drinking water, diet, and defecation were normal, and there were no abnormal secretions in the mouth, nose, ears, etc., and no dead rats were observed. After the end, the rats in each group were dissected, and important organs such as the brain, lung, stomach, intestine, kidney, and liver of the rats were taken for histopathological examination. Coagulation necrosis of glomerular tubules, no obvious special glomerular tubules, no hyaline sclerosis of afferent arterioles, and no abnormalities were found in other groups. In all groups, there was no abnormality in cerebellum, brain, lung, liver, and intestine.

5.2 Comparison of the weight growth of the rats with the blank control group, the results are shown in Table 1 and Table 2.

Changes in rat body weight in the complete skin acute toxicity test of table 1 ( n=8, g)

Changes in rat body weight in table 2 damaged skin acute toxicity test ( n=8, g)

Among them, * indicates that compared with Comparative Example 2, P<0.05; △ indicates that compared with the blank group, P<0.05.

As can be seen from Table 1 and Table 2, in the mice with intact skin, the body weight of each time point after the administration is compared with the Example 1 group, the Example 2 group, and the Example 3 group compared with the Comparative example 1 group and the Comparative example 2 group. There was no significant difference in the increase (P>0.05), and there was no significant difference in the weight gain of rats in the above five groups at each time point compared with the blank group (P>0.05). In the mice with damaged skin, from the 7th day after the medication, the body weight gain of the rats in the Example 1 group, the Example 2 group, and the Example 3 group was gradually greater than that of the Comparative Example 2 group, and began to appear significantly on the 10th day. Difference (P＜0.05), the body weight gain of embodiment 1 group, embodiment 2 group, embodiment 3 group and comparative example 1 group is compared with blank group and does not show significant difference (P＞0.05), comparative example Compared with the blank group, there was a significant difference between the two groups (P<0.05), indicating that the transdermal patch prepared in the comparative example 2 group may have acute toxicity to rats with damaged skin, while other groups have no acute toxicity on rats.

2. Skin irritation

1. Method

Get 100 guinea pigs, divide them into groups according to the random number table method, divide the guinea pigs into complete embodiment 1 group, complete embodiment 2 group, complete embodiment 3 group, complete comparative example 1 group, complete comparative example 2 groups and damaged embodiment 1 group, 2 groups of damaged examples, 3 groups of damaged examples, 1 group of damaged comparative examples, 2 groups of damaged comparative examples, 10 rats in each group.

Using the left and right comparison method of the same body, the test drug was applied to the left hair removal area, and the right side was used as a blank control group, which was divided into intact skin and damaged skin. The hair on both sides of the guinea pig spine was removed 24 hours before administration, accounting for about the body surface area. 10% of.

Production of damaged skin: Use a blunt blade to cut the depilated and disinfected skin to the degree of bleeding. The degree of damage to the skin on the left and right sides should be basically the same. The patches prepared by each group were applied externally on the left depilated area, and the metabolic cages were kept in separate cages. After 4 hours of application, the residual test substance was removed with warm water. Thereafter, the skin reaction was observed at 1, 24, 48, and 72 hours. Score and record according to Table 3 and evaluate the skin irritation of the test drug according to Table 4.

Table 3 Scoring Criteria for Skin Irritation

Table 4 Scoring criteria for skin irritation intensity

average score Evaluation 0～0.49 non-irritating 0.5～2.99 mild irritant 3.0～5.99 Moderate irritation 6.0～8.0 strong irritant

2. Statistical methods

Statistical analysis was performed using SPSS17.0. The mean value of the experimental data is express.

3. Results

The skin irritation test results of each group are shown in Table 5 and Table 6.

Table 5 Irritation score of guinea pigs in complete skin group

Table 6 Irritation score of guinea pigs in damaged skin group

Under a certain dose, the intact skin groups all showed that each group of the embodiment had no stimulating effect on the skin between 1 hour and 72 hours, and the comparative example 1 group and the comparative example 2 group had a slight stimulating effect at 24 hours, and after 48 hours Stimulation disappears gradually; Damaged skin group shows that each embodiment group occurs extremely slight in 24h, can be counted as non-irritating stimulation, and disappears gradually after 48h; Comparative example 1 group occurs mild skin irritation in 24 hours, in 24 hours It gradually disappeared after 48 hours; mild skin irritation occurred in the control group 2 at 24 hours, and persisted at 48 hours and 72 hours.

3. Evaluation of analgesic effect

1. Instruments and reagents

BW-HB803 intelligent hot plate instrument (Shanghai Ruanlong Technology Development Co., Ltd.); sodium chloride;

Healthy Kunming mice, weighing 18-22g, were purchased from Guangzhou Saibainuo Biotechnology Co., Ltd.

2. Administration method

The pain domain was measured on 60 female mice, and the mice with hypersensitivity or insensitivity to pain and happy jumping should be discarded. Qualified mice were randomly divided into six groups: Example 1 Group, Example 2 Group, Example 3 Group, Blank Control Group, Comparative Example 1 Group, and Comparative Example 2 Group.

The blank control group was given a blank patch of the same size as the application; the daily administration area of the animals: 2×2cm ² .

3. Experimental method

Healthy female mice were taken, and the abdomen of the mice in each group was plucked, and then depilated with 8% sodium sulfide, with an area of 2×2 cm ² .

thermal stimulation

Keep the room temperature at 15-20°C, adjust the constant temperature self-control hot plate apparatus to adjust the temperature to 55±0.5°C, take one female mouse each time, place it on the hot plate apparatus, and record the time required from putting it in to licking the hind paw (s), measure the pain threshold of the mouse, re-test after 5 minutes, if the two pain responses all occur within 5-30 seconds, then it is qualified. Mice that are overly sensitive or insensitive to pain and those that like to jump and flee should be discarded. The mean of two normal pain response times of qualified mice was calculated as the average pain response time (ie pain threshold) before administration. Qualified mice will be selected for random grouping, and corresponding drug patches will be given respectively. Each group was administered continuously for 3 days, twice a day. On the fourth day, the pain threshold was measured at 5 minutes, 10 minutes and 20 minutes after the administration of each group. If the mice did not experience pain within 60 seconds, it was counted as 60 seconds. The percentage increase of pain threshold was calculated according to the mean value of pain threshold measured at different times in each group.

calculation method

4. Statistical processing methods

data adoption The paired t-test was used for comparison before and after administration, and the between-group t-test was used for comparison between groups.

5. Results

The results are shown in Table 7.

The analgesic effect ( n=10)

Among them, * means P<0.05 compared with blank group; △ means P<0.05 compared with control group 1 and 2.

It can be seen from Table 7 that the percentage increase of the pain threshold of each group in the examples exceeds 70%, indicating that the transdermal patch prepared by the present invention has a better analgesic effect. Compared with each group of the comparative example, the pain threshold of each group of the embodiment was significantly improved after 20 minutes of administration (P<0.05); compared with the blank group, the pain threshold of each group of the embodiment of the administration was significantly improved after 20 minutes of administration (P<0.05) .

It should be noted that when a numerical range is involved in the claims of the present invention, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. 3 Similarly, to avoid redundancy, the present invention describes preferred embodiments, but those skilled in the art can make additional changes and modifications to these embodiments once the basic inventive concepts are known. Therefore, it is intended that the appended claims be construed to cover the preferred embodiment as well as all changes and modifications which fall within the scope of the invention.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit and scope of the invention. Thus, provided that these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims (10)

1. A composite transdermal patch for the treatment of chronic pain, characterized in that it is made of the following components in parts by weight: 10-20 parts of Safflower, 20-35 parts of Corydalis Corydalis, 5-35 parts of Radix Paeoniae Rubra 8 parts, 3-5 parts of lidocaine hydrochloride injection, 1-3 parts of mixture of betamethasone dipropionate and betamethasone sodium phosphate, 1-3 parts of compound penetration enhancer; Wherein, the mass ratio of betamethasone dipropionate to betamethasone sodium phosphate is 3-5:2. 2. The composite transdermal patch for treating chronic pain according to claim 1, characterized in that it is made of the following components in parts by weight: 15 parts of safflower, 28 parts of Corydalis Corydalis, 6 parts of Radix Paeoniae Rubra 5 parts of lidocaine hydrochloride injection, 3 parts of betamethasone dipropionate and betamethasone sodium phosphate mixture, 1 part of compound penetration enhancer; Wherein, the mass ratio of said betamethasone dipropionate to betamethasone sodium phosphate is 4:2. 3. The compound transdermal patch for treating chronic pain according to claim 1 or 2, characterized in that the concentration of lidocaine hydrochloride in the lidocaine hydrochloride injection is 0.1g/5mL. 4. the compound transdermal patch for the treatment of chronic pain according to claim 1 or 2, is characterized in that, described compound penetration enhancer is selected from ethanol, propylene glycol, fatty acid ester, dimethyl sulfoxide and its Congeners, oleic acid, linoleic acid, lauryl alcohol, azone and its homologues, sodium lauryl sulfate, Tween-80, urea, salicylic acid, pyrrolidones, menthol, camphor, limonene, eucalyptol one or more of. 5. The composite transdermal patch for treating chronic pain according to claim 4, wherein the composite penetration enhancer is composed of ethanol, menthol and camphor in a mass ratio of 3:3:4. 6. the preparation method of the composite transdermal patch for the treatment of chronic pain according to claim 1, is characterized in that, specifically operates according to the following steps: Step 1. Weigh 10-20 parts of safflower, 20-35 parts of Corydalis Corydalis, 5-8 parts of Radix Paeoniae Rubra, 3-5 parts of lidocaine hydrochloride injection, betamethasone dipropionate and betamethasone dipropionate in parts by weight. 1-3 parts of metasone sodium phosphate mixture, 1-3 parts of compound penetration enhancer; Wherein, the mass ratio of said betamethasone dipropionate to betamethasone sodium phosphate is 3-5:2; Step 2, pulverizing the safflower, corydalis, and red peony root weighed in step 1, sieving, and mixing uniformly to obtain a solid powder mixture; Step 3, mix the lidocaine hydrochloride injection, betamethasone dipropionate and betamethasone sodium phosphate mixture, composite penetration enhancer and step 2 obtained in step 1, and then press its Add 60-80% of the binder by total weight, stir evenly, and degas to obtain the drug mixture; Step 4. Apply the drug mixture obtained in Step 3 on a release paper, cover with a release-controlling film after drying, cut, seal and package to obtain a composite transdermal patch. 7. The preparation method of the composite transdermal patch for treating chronic pain according to claim 6, characterized in that the sieving in step 2 is 200-mesh sieve. 8. The preparation method of the composite transdermal patch for treating chronic pain according to claim 6, characterized in that, the adhesive is an acrylate copolymer emulsion. 9. the preparation method of the compound transdermal patch that is used for the treatment of chronic pain according to claim 6, it is characterized in that, described controlled-release film is selected from ethylene-vinyl acetate copolymer film, polyvinyl chloride film, polyethylene One of membrane or microporous polypropylene membrane. 10. The method for preparing the composite transdermal patch for treating chronic pain according to claim 9, characterized in that the release-controlling film is a polyethylene film.