CN115531505B

CN115531505B - Traditional Chinese medicine gel plaster for osteoarthritis inflammation resistance and pain relief and preparation method thereof

Info

Publication number: CN115531505B
Application number: CN202211257426.6A
Authority: CN
Inventors: 王培民; 茆军; 刘子修; 张农山; 张立; 邢润麟; 黄正泉; 刘史佳
Original assignee: Jiangsu Provincial Hospital of Chinese Medicine
Current assignee: Jiangsu Provincial Hospital of Chinese Medicine
Priority date: 2021-12-22
Filing date: 2022-10-13
Publication date: 2023-03-31
Anticipated expiration: 2042-10-13
Also published as: CN114209799A; CN115531505A

Abstract

The invention discloses a traditional Chinese medicine gel plaster for osteoarthritis anti-inflammatory analgesia and a preparation method thereof, wherein the traditional Chinese medicine gel plaster comprises a back lining layer, a plaster layer and an anti-sticking film; the plaster layer is a gel layer formed by the traditional Chinese medicine composition and a substrate for loading the traditional Chinese medicine composition. The traditional Chinese medicine composition comprises 15-18 parts of fructus viticis, 15-18 parts of cortex cercis chinensis, 3-5 parts of angelica sinensis, 3-5 parts of pawpaw, 3-5 parts of salvia miltiorrhiza, 3-5 parts of red peony root, 3-5 parts of angelica dahurica, 3-5 parts of rhizoma wenyujin concinnatae, 3-5 parts of radix angelicae pubescentis, 3-5 parts of notopterygium root, 3-5 parts of trichosanthes root, 3-5 parts of radix cyathulae, 3-5 parts of radix clematidis, 3-5 parts of radix stephaniae tetrandrae, 3-5 parts of radix sileris, 3-5 parts of nux vomica, 2-3 parts of ligusticum wallichii, 2-3 parts of gentiana macrophylla, 2-3 parts of fructus forsythiae and 1-2 parts of liquorice. The matrix comprises glycerol, EDTA, dihydroxyaluminum, sodium polyacrylate, water, EM-178, AC-10H, penetration enhancer, antiseptic and tartaric acid. The gel plaster obtained by the invention has the advantages of convenient use, controllable administration dosage, good adhesiveness, continuous effect and good skin following property, can provide reference for the reform of similar external preparation dosage forms, and is convenient for clinical popularization and use.

Description

Traditional Chinese medicine gel plaster for osteoarthritis anti-inflammatory and analgesic and preparation method thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine gel plaster for osteoarthritis inflammation resistance and pain relief.

Background

Osteoarthritis is an intact joint disease involving structural changes in hyaline articular cartilage, subchondral bone, ligaments, joint capsule, synovium, and the muscles surrounding the joint. Due to the aging world population, the rise in obese people, and the increasing number of joint injuries, osteoarthritis has become a serious disease that is common in life, affecting affected individuals, health care systems, and socioeconomic costs. And some other syndromes are increasing year by year, it is estimated that 2.5 million people are currently affected worldwide.

The gonarthromeningitis refers to a noninfectious inflammatory reaction of synovial membrane injury and rupture caused by acute trauma or chronic strain and other stimulation to cause abnormal function, joint fluid cannot be normally generated and absorbed, and hematocele or hydrops in knee joint cavities are caused. Gonarthromeningitis lesions are important factors in the occurrence of knee osteoarthritis and are often used as a signal for the prevention and treatment of knee osteoarthritis. The research shows that: inflammation in synovitis or effusion is the major cause of pain in knee osteoarthritis.

The most common treatment for osteoarthritis today is oral paracetamol, a non-steroidal anti-inflammatory drug or an intra-articular injection. However, the amount of action of paracetamol is very small compared to placebo, and combined with safety issues, it is of little use as a single drug for the treatment of osteoarthritis; long-term use of nonsteroidal anti-inflammatory drugs can cause adverse reactions, such as peptic ulcer and bleeding; the injection of drugs into the joint cavity is likely to cause infection. Compared with oral administration or injection therapy, the application therapy is not easy to cause gastrointestinal adverse reactions and cardiovascular diseases. In clinic, the cerealose and the medicinal powder are used for on-site modulation, so that the medicine carrying amount is limited, certain stimulation is caused to the skin, the medicine is inconvenient to store and carry, and the bioavailability of the medicine is limited.

Disclosure of Invention

The purpose of the invention is as follows: the invention aims to solve the technical problem of the prior art, provides a traditional Chinese medicine gel plaster for osteoarthritis anti-inflammatory analgesia and a preparation method thereof, exerts the effects of traditional Chinese medicine compatibility anti-inflammatory analgesia and gel in-vitro transdermal permeation promotion, and is convenient for clinical popularization and use.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

a Chinese medicinal gel plaster for treating osteoarthritis and relieving inflammation and pain,

the composition comprises the following components in parts by mass: comprises a back lining layer, a paste layer and an anti-sticking film; the plaster layer is a gel layer formed by the traditional Chinese medicine composition and a substrate for loading the traditional Chinese medicine composition;

the traditional Chinese medicine composition comprises the following components in parts by weight:

15 to 18 parts of fructus viticis, 15 to 18 parts of Chinese redbud bark, 3 to 5 parts of angelica, 3 to 5 parts of pawpaw, 3 to 5 parts of salvia miltiorrhiza, 3 to 5 parts of red peony root, 3 to 5 parts of angelica dahurica, 3 to 5 parts of rhizoma wenyujin concinnae, 3 to 5 parts of radix angelicae pubescentis, 3 to 5 parts of notopterygium root, 3 to 5 parts of trichosanthes root, 3 to 5 parts of radix cyathulae, 3 to 5 parts of radix clematidis, 3 to 5 parts of radix stephaniae tetrandrae, 3 to 5 parts of divaricate saposhnikovia root, 3 to 5 parts of nux vomica, 2 to 3 parts of ligusticum wallichii, 2 to 3 parts of gentiana macrophylla, 2 to 3 parts of fructus forsythiae and 1 to 2 parts of liquorice;

the matrix of the plaster layer comprises glycerol, EDTA, aluminum glycollate, sodium polyacrylate, water, EM-178, AC-10H, penetration enhancer, antiseptic and tartaric acid.

Preferably, the traditional Chinese medicine gel plaster for osteoarthritis anti-inflammatory analgesia comprises the following components in parts by mass:

16 parts of fructus viticis, 16 parts of cortex cercis chinensis, 4 parts of angelica sinensis, 4 parts of pawpaw, 4 parts of salvia miltiorrhiza, 4 parts of red peony root, 4 parts of angelica dahurica, 4 parts of rhizoma wenyujin concinnatae, 4 parts of radix angelicae pubescentis, 4 parts of notopterygium root, 4 parts of trichosanthes root, 4 parts of radix cyathulae, 4 parts of radix clematidis, 4 parts of radix stephaniae tetrandrae, 4 parts of radix sileris, 4 parts of nux vomica, 2 parts of ligusticum wallichii, 2 parts of gentiana macrophylla, 2 parts of fructus forsythiae and 1 part of liquorice.

The medicine collocation principle of the traditional Chinese medicine composition for osteoarthritis anti-inflammatory analgesia of the invention is as follows: the whole prescription takes the fructus viticis and the Chinese redbud bark as the monarch drugs, and has the effects of dispersing the cold and heat between bones, eliminating dampness, arthralgia and contracture, activating blood circulation, stimulating the menstrual flow, relieving swelling and alleviating pain; the ministerial drugs such as angelica, rhizoma ligustici wallichii, gentiana macrophylla, salvia miltiorrhiza and the like which can warm the channels and promote blood circulation are used for warming the channels and dredging the collaterals and easing joint movement; the notopterygium root, the radix angelicae pubescentis and the radix cyathulae are used for dispersing rheumatism on the upper and lower parts of the body and easing joint movement to stop arthralgia; the Chinese clematis, the nux vomica, the pawpaw, the angelica dahurica, the red paeony root and the rhizoma wenyujin concinnatae are added for strengthening the functions of dispelling wind-damp, stopping arthralgia and removing blood arthralgia, and the forsythia and the trichosanthes root have the functions of clearing heat and promoting the production of body fluid, reducing swelling and expelling pus, and the gentiana macrophylla has the functions of preventing wind and leveling without dryness and dispelling wind-damp and clearing damp-heat; finally, blending with liquorice. All the above Chinese medicinal powders are purchased from Wansheng Chinese medicinal decoction pieces Limited company of Anhui, china Anhui, and identified by the professor of Wangbei schoenzi (Nanjing, china) of the subsidiary hospital of Nanjing Chinese medicinal university. The medicinal materials selected by the prescription after being processed reach the application standard of clinical decoction pieces, and the medicinal materials are externally applied in the form of external preparations and are clinically blended and externally applied according to the traditional maltose for a long time, so the safety and the effectiveness are verified in the long-term and large-scale application process. Therefore, the anti-inflammatory analgesic osteoarthritis formula has good application value in the aspect of developing and preparing products for treating osteoarthritis.

In the traditional Chinese medicine gel plaster, the backing layer is the carrier part of the gel plaster, mainly provides a medicine carrying platform and a protection function, and uses non-woven fabrics commonly used in the field. The anti-sticking film is a surface covering part and is used for protecting the matrix layer and preventing the medicine from leaking in the storage process, and the embossing film with the adhesive surface for gluing is selected; the matrix of the plaster layer comprises glycerol, EDTA, aluminum glycollate, sodium polyacrylate, water, EM-178, AC-10H, penetration enhancer, antiseptic and tartaric acid.

The forming process of the preparation of the Chinese medicinal gel plaster is more complicated than that of the matrix, and the influence factors are more. On one hand, the physicochemical properties of the medicine are considered, on the other hand, the proportion and compatibility of the matrix and the raw material medicine are also considered, and the addition of the medicine can influence the properties of the matrix, so that the prepared gel emplastrum cannot reach the optimal performance, and the exertion of the advantages of the gel emplastrum is influenced. The invention takes water-soluble high molecular material as a framework, is uniformly mixed with the medicinal powder extract and then is coated on a backing material to prepare the traditional Chinese medicine gel emplastrum, which has a targeted instantaneous potential ion channel, intervenes in a KOA peripheral pain-sensitive link, blocks the conduction of temperature and pressure nociceptors to pain signals and obviously increases the cold pain threshold and the mechanical pain threshold of a KOA model animal; it also can inhibit NLRP3 inflammation pathway, relieve KOA joint stiffness, and improve joint function. Compared with the traditional preparation, the preparation has good compatibility with skin and small irritation; the drug loading capacity is larger; improving horny layer and increasing the bioavailability of the medicine; the administration frequency is reduced, and the medication compliance is improved; convenient use, no pollution to clothes and repeated adhesion.

Preferably, in the ointment layer, the drug-loading rate of the aqueous extract, the alcohol extract, the volatile oil, the mixed ointment preparation or the medicinal powder of the traditional Chinese medicine composition is 10 to 25wt.%.

Specifically, the mass ratio of each component in the paste layer is as follows: glycerol, EDTA, glycollic aluminum, sodium polyacrylate, water, chinese medicinal composition powder, EM-178, AC-10H, penetration enhancer, preservative and tartaric acid = (250-400 g), (0.5-1.5 g), (1.0-3.0 g), (40-60 g), (200-300 g), (150 g), (100-200 g), (20-40 ml), (0.5-2 ml), (2.0-4.0 g), preferably 330g.

In the traditional Chinese medicine gel plaster for osteoarthritis anti-inflammatory and analgesia, sodium polyacrylate is used as a framework material, dihydroxyaluminum glycinate is used as a cross-linking agent, EM-178 (Jurymer R EM-178 produced by TOAGOSEI CO LTD. Company) and AC-10H (Jurymer AC-10H produced by TOAGOSEI CO LTD. Company) are used as viscosity increasers, glycerol is used as a humectant, and tartaric acid is used as a cross-linking regulator. The research finds that the dosage of the sodium polyacrylate and the aluminum dihydroxylate in the formula has a direct relation with the viscosity and the strength of the prepared anti-inflammatory analgesic gel paste, and when the dosage is lower, the crosslinking degree of the matrix is lower, the whole body is loose, the viscosity is low, the paste rigidity is poorer, the residual quantity is large, the paste is easy to be removed, and the like; when the dosage is high, the crosslinking degree of the matrix is high, the whole body is compact, the viscosity is high, and gel paste cannot be formed. The dosage of glycerin is too small, the ointment is easy to become hard, the dosage is too much, and the ointment is too thin. Tartaric acid is used as a crosslinking regulator, can regulate the crosslinking speed of the paste, is not easy to coat when the crosslinking is too fast, can balance and regulate the pH value of a reaction environment, assists in regulating the crosslinking of sodium polyacrylate and aluminum glycollate, and gives full play to the viscosity of a system.

Preferably, the penetration enhancer is any one or a mixture of more than two of menthol, camphor, borneol or azone;

most preferably, the penetration enhancer is a mixture of menthol and camphor.

The invention prepares the gel emplastrum with the best performance by screening the composition and the proportion of the matrix, optimizing the proportion of the matrix and the medicine on the basis and combining the matrix forming process and the preparation forming process. Therefore, the preparation method of the traditional Chinese medicine gel plaster for osteoarthritis anti-inflammatory analgesia is also in the protection application of the invention, and the preparation method specifically comprises the following steps:

s1: adding EDTA, dihydroxyaluminum glycolate and sodium polyacrylate into glycerol, and uniformly stirring in a reaction kettle to obtain phase A;

s2: adding EM-178, AC-10H, penetration enhancer, antiseptic and Chinese medicinal powder into water, stirring and mixing to obtain phase B;

s3: adding tartaric acid into water, and performing ultrasonic dispersion to obtain a C phase;

s4: mixing phase A, phase B and phase C, stirring under vacuum, coating on backing layer, and covering with anti-sticking film.

In the preparation process, the glycerol also has the function of primarily dispersing the water-soluble high molecular compound, and when the water-soluble high molecular material is directly dispersed in water, the water is easily absorbed to form material lumps, namely gel lumps, which are not easy to disperse. Therefore, the preparation steps of the experiment are that the sodium polyacrylate is firstly dispersed in the glycerol system to be uniformly dispersed, and then a proper amount of water is added into the glycerol system to form the gelatinous substrate.

Preferably, in step S1, the mass ratio of aluminum glycoxide, sodium polyacrylate, EDTA and glycerin is 1.0 to 3.0 g.

Preferably, in the step S2, the dosage ratio of EM-178, AC-10H, penetration enhancer, preservative, chinese medicinal composition powder to water is 100-200g; most preferably 150g;

preferably, in step S3, the ratio of tartaric acid to water is 2.0 to 4.0 g. The backing layer is the carrier part of the gel emplastrum, mainly provides a drug-loading platform and a protection function, and uses non-woven fabrics commonly used in the field.

The anti-sticking film is a surface covering part for protecting the matrix layer and preventing the medicine from leaking in the storage process, and the embossing film with the adhesive surface for gluing is selected.

Furthermore, the invention also claims the application of the traditional Chinese medicine gel plaster in preparing the anti-inflammatory analgesic medicine for treating osteoarthritis.

Compared with the prior art, the invention has the beneficial effects that:

(1) The anti-inflammatory analgesic gel plaster developed based on the anti-inflammatory analgesic traditional Chinese medicine formula has the advantages that the gel plaster obtained through reasonable proportioning of the matrix and the traditional Chinese medicine components is convenient to use, controllable in administration dosage, good in adhesion, continuous in effect taking and good in skin following performance, solves the problems that a traditional Chinese medicine anti-inflammatory analgesic compound preparation is not extracted, coarse in administration mode, prone to polluting clothes, inaccurate in dosage, poor in adhesion, poor in medicine permeability, unstable in curative effect and the like, can provide reference for formulation reformation of similar external preparations, and facilitates clinical popularization and use.

(2) The application therapy does not detect obvious hepatotoxicity and kidney toxicity through a transdermal drug delivery system, is not easy to cause gastrointestinal adverse reactions and cardiovascular diseases compared with oral administration or injection therapy, and is one of the representatives of the traditional application therapy by the 'easy-layer' application of a preparation optimized and named by 'Shi traumatology' in the hospital in Jiangsu province and traditional Chinese medicine. Since the last 50 years, the traditional Chinese medicine hospital in Jiangsu province has the advantages that the prescription is used for treating symptoms such as KOA pain and joint swelling, the curative effect is obvious, and the prescription is widely praised by patients. The Chinese medicinal composition 'triple dispersion' formula is an important component for 'easy-layer' application. In the clinical application of 'triple dispersion', the cerealose and the medicinal powder are used for on-site modulation for administration, the drug loading is limited, certain stimulation is caused to the skin, the storage and carrying are inconvenient, and the bioavailability of the medicament is limited. According to the invention, by optimizing the dosage form, compared with the original application, the screened gel emplastrum has better skin compatibility and small irritation; the drug loading capacity is larger; can improve horny layer and improve the bioavailability of the medicine; is suitable for cleaning and can be repeatedly pasted; the product can be industrially produced in batches, can be stored and transported for a long time, and is convenient for clinical popularization and use.

Drawings

FIG. 1 shows the preparation process of the gel plaster.

FIG. 2 shows the expression results of synovial IL-1 β, TNF- α, IL-6 proteins.

FIG. 3 shows the results of synovial membrane expression of IL-1 β, TNF- α, and IL-6 mRNA.

Detailed Description

The invention will be better understood from the following examples.

Example 1

The Chinese medicinal decoction pieces with the anti-inflammatory and analgesic composition are weighed according to the proportion in the following table 1.

Then preparing the Chinese medicinal composition powder according to the following preparation process:

extracting 1kg of Chinese medicinal decoction pieces with 55% ethanol in an amount eight times of the decoction pieces for 1.5 hr, filtering, extracting the residue with 55% ethanol in an amount eight times of the decoction pieces for 1.5 hr, filtering, collecting the filtrate, concentrating, and drying to obtain medicinal powder.

TABLE 1

Model group: 10 molded rats were taken and no drug was administered.

The original process group is as follows: the powder was mixed with maltose at a ratio of 1.

Gel plaster group: the drug loading of the matrix was 15wt.%, and about 1.5g of each rat was administered to 10 molded rats. Gel patches were prepared according to the procedure shown in fig. 1:

s1, adding EDTA0.9g, dihydroxyaluminum glycinate 1.8g and sodium polyacrylate 58g into glycerol 330g, and uniformly stirring in a reaction kettle to obtain a phase A;

s2, adding EM-178150g, AC-10H100g, preservative 150g and medicinal powder into 200g of purified water, and uniformly stirring to obtain a phase B;

s3, adding 2.5g of tartaric acid into 62.2g of water, and dissolving by ultrasonic to obtain a C phase;

and S4, mixing the A, the B and the C, uniformly stirring in vacuum, coating on a back lining layer, and covering an anti-sticking film to obtain the gel plaster.

Gel patch (penetration enhancer) group: the drug loading of the matrix was 15wt.%, and about 1.5g of each rat was administered to 10 molded rats. The preparation steps of the gel plaster (penetration enhancer) are the same as those of the gel plaster group, except that 30g of menthol and camphor are also added in the step S2.

Blank group: 10 healthy rats were taken.

Animal drug effect experiment of gel emplastrum

1. Experimental method

(1) Establishment of rat knee osteoarthritis model

35 rats are taken, each rat is injected with chloral hydrate for anesthesia and the knee joint is disinfected, the medial incision beside the left patella is taken to expose the knee joint, the joint capsule is cut, the joint cavity is opened, and the inside and the outside of the patella are dislocated. And then the knee joint is bent as much as possible to expose the anterior cruciate ligament, and the anterior cruciate ligament is cut off under the direct vision of a small pointed knife. Drawer experiments were then performed to determine anterior cruciate ligament rupture. Then stopping bleeding completely, resetting the patella and closing the incision layer by layer. Penicillin was again administered once a day at 40 μm for 3 consecutive days.

(2) Rat experimental grouping

The original process group is as follows: 10 molded rats were dosed with about 1g of drug per rat.

Gel plaster group: 10 molded rats were dosed with about 1.5g of drug per rat.

Gel patch (penetration enhancer) group: 10 molded rats were dosed with about 1.5g of drug per rat.

Model group: 10 molded rats were taken and no drug was administered.

Blank group: 10 healthy rats were taken.

(3) Cold and hot plate pain test

The rats in 5 groups were placed on a cold plate apparatus at 55 + -0.5 deg.C, and 5 rats per group were tested using the time from the start of the test to the time of foot licking after the first time as an index of pain response. And its pain threshold (seconds, s) was recorded.

(4) Results of the experiment

Table 2 and table 3 show the pain thresholds (seconds, s) of rats for the hot plate method and the cold plate method, respectively.

TABLE 2

TABLE 3

The best therapeutic effect of the patch group (penetration enhancer) is shown in the experimental results of tables 2 and 3.

Example 2

Intervention effect of gel emplastrum on KOA rat synovitis

Preparation of synovial membranes of rats

5 male SD rats which were successfully molded by cervical dislocation, were sterilized, then the knee joints were cut, synovial tissues were taken out, andthe cells were placed in sterile phosphate buffered saline (PBS, pH 7.4) and washed repeatedly 3 times. Cutting the above tissue into small pieces of about 1mm × 1mm with scissors, and digesting with 0.2% collagenase type I at 37 deg.C for 2 hr; after filtration through a 70 μm sieve, the precipitate was centrifuged at 1000r/min for 5min, resuspended in a cell culture dish using DMEM medium containing 10% fetal bovine serum and 1% penicillin-streptomycin double antibody, and the CO was 5% at 37 deg.C ₂ The cells were incubated overnight in a cell incubator, and the medium was changed after 24 hours, followed by 1 change every 2 days. When the cells are fused to 80-90%, 0.25% pancreatin is used for digestion and passage. Experiments were performed using passage 3-6 cells to ensure their activity and biological properties.

Synovial cell culture

A blank group (A) without cells and medicines is firstly arranged, then the cells are randomly divided into a model group (B), a gel plaster group (penetration enhancer) (C), a gel plaster group (D) and an original process group (E), and each group is provided with 3 compound holes. The medium, blank and model groups were aspirated into 100. Mu.L of complete medium, and 100. Mu.L of complete medium containing the corresponding drug was added to each administration group.

Detection of inflammatory factors

And detecting by using an ELISA method. After each group of cells was cultured for 24h, the supernatant was collected, and OD values of each group were measured at a wavelength of 450nm with a microplate reader, strictly according to the instructions of the respective kit, and IL-6, IL-1. Beta. And TNF-. Alpha. Levels were calculated from the standard curves.

Statistical method

Statistical analysis of the data was performed using SPSS 20.0 software and plotted using Graphpad 7.04 software. The experimental data are expressed as x ± s, and the single-factor analysis of variance was used for the comparisons between groups, and the LS D test (uniform variance) or Dunnett's T3 test (non-uniform variance) was used for pairwise comparisons between groups. Inspection level α =0.05.

The result of the detection

1. Grading of synovial inflammation in rats

Rat synovial inflammation was graded using the Krenn score, which is reported in the literature:

V.Krenn.Grading of Chronic Synovitis-A Histopathological Grading Sys tem for Molecular and Diagnostic Pathology.PATHOLOGY RESEARCH AND PRACTICE.

TABLE 4 Krenn score and ranking of synovial inflammation in rats

2. Synovial IL-1 beta, TNF-alpha, IL-6 protein expression

The results are shown in FIG. 2: p <0.05 compared to blank a pair; compared to model B group, # P <0.05; compared with the gel plaster D group and the original process E group, & P is less than 0.05; compared with gel plaster (penetration enhancer) group C, P is less than 0.05.

It can be seen that: compared with a blank group, the expression level of the proinflammatory factor proteins of IL-1 beta, TNF-alpha and IL-6 in the model group is obviously increased; the expression of inflammatory factor protein in an administration group is inhibited, wherein the effect of a gel plaster (penetration enhancer) group is optimal, and the gel plaster dosage form using the penetration enhancer can play a better anti-inflammatory effect.

3. Synovial IL-1 beta, TNF-alpha, IL-6mRNA expression

The results are shown in FIG. 3: p <0.05 compared to blank a pair; compared to model B group, # P <0.05; compared with the gel plaster group D and the original technology group E, & P & lt 0.05; compared with gel plaster (penetration enhancer) group C, P is less than 0.05.

It can be seen that: compared with a blank group, the model group has obviously increased expression levels of IL-1 beta, TNF-alpha and IL-6 proinflammatory factor mRNA; the expression of the inflammatory factor mRNA in the administration group is inhibited, wherein the gel plaster (penetration enhancer) group has the best effect.

Example 3

Single factor investigation of gel plaster matrix

1. Investigation of sodium polyacrylate dosage

(1) The preparation method of the medicinal material extract comprises weighing pulverized medicinal material coarse powder, reflux-extracting with 8 times of 55% ethanol for 2 times, each for 90min, mixing filtrates, filtering, and concentrating to concentration of 1g of the raw medicinal material per 1ml to obtain medicinal material extract.

(2) The amount of the components

The dosages of the glycerin are controlled to be 200g, the tartaric acid is 2.5g, the medicinal powder is 150g, the dihydroxyaluminum aminoacetate is 1.8g, and the dosages of the sodium polyacrylate are respectively controlled to be 40g, 46g, 52g and 60g.

(3) Preparation method of gel plaster

S1, adding EDTA, dihydroxyaluminum glycolate and sodium polyacrylate into glycerol, and uniformly stirring in a reaction kettle to obtain phase A;

s2, adding EM-178, AC-10H, menthol, camphor, preservative and medicinal powder into purified water, and uniformly stirring to obtain a phase B;

s3, adding tartaric acid into water, and dissolving by ultrasonic to obtain a C phase;

and S4, mixing the A, the B and the C, uniformly stirring in vacuum, coating the mixture on a back lining layer, and covering an anti-sticking film to obtain the gel plaster.

(4) Analysis of results

The initial adhesion, holding power and peel strength are used as evaluation indexes, and the optimum amount range of sodium polyacrylate is preferable.

As a result, the optimum amount of sodium polyacrylate was determined to be 52g.

The results of examining the amount of sodium polyacrylate are shown in Table 5.

TABLE 5

2. Investigation of glycerol dosage

(1) The preparation of the traditional Chinese medicine extracting solution is the same as the investigation of the using amount of the sodium polyacrylate.

(2) The dosage of the sodium polyacrylate is controlled to be 52g, the dosage of the medicine extracting solution is 150g, the dosage of the dihydroxyaluminium aminoacetate is 1.8g, the dosage of the tartaric acid is 2.5g, and the dosage of the glycerol is controlled to be 250g, 300g, 350g and 400g.

(3) The gel paste is prepared according to the preparation method of the gel paste in the investigation of the use amount of the sodium polyacrylate.

(4) Analysis of results

The initial adhesion, holding power and peel strength are used as evaluation indexes, and an optimum amount range of glycerin is preferred.

As a result, the optimum amount of glycerin was determined to be 300g.

The results of the investigation of the amount of glycerol are shown in Table 6.

TABLE 6

3. Examination of tartaric acid dosage

(2) The dosage of sodium polyacrylate is controlled to be 52g, the dosage of the medicine extract is 150g, the dosage of the dihydroxyaluminium aminoacetate is 1.8g, the dosage of the glycerol is 200g, and the dosage of the tartaric acid is controlled to be 2.0g, 2.5g, 3.0g and 3.5g.

(4) Analysis of results

The initial adhesion, holding power and peel strength were used as evaluation indexes to examine the influence of the amount on the substrate properties. The results are shown in the table. As a result, it was found that when the amount of tartaric acid used was 2.0g, the initial adhesion, adhesive force, holding force and peel strength of the substrate were the best. In the experimental process, the fact that the fluidity of the matrix is larger and larger, the crosslinking is slower and slower, and the forming time is longer and longer in the process of mixing the phase A and the phase B added with the liquid medicine along with the increase of the dosage of the tartaric acid is found, so that the optimal dosage of the tartaric acid is 2.0g.

The results of the tartaric acid dosage investigation are shown in Table 7.

TABLE 7

4. Investigation of amount of aluminum glycollate

(2) The dosage of sodium polyacrylate is controlled to be 52g, the dosage of the medicine extract is 150g, the dosage of glycerin is 200g, the dosage of tartaric acid is 2.5g, and the dosage of dihydroxyaluminum glycinate is controlled to be 1.0g, 1.5g, 1.8g and 2.3g.

(4) Analysis of results

As a result, it was confirmed that the optimum amount of aluminum chlorohydrate was in the range of 1.8g,

the results of the study of the amount of dihydroxyaluminum glycinate are shown in Table 8.

TABLE 8

Orthogonal design optimization prescription

Based on the previous literature research and single-factor experiment, sodium polyacrylate (A), glycerol (B), dihydroxyaluminum glycinate (C) and tartaric acid (D) are selected as investigation factors, and initial adhesion, holding adhesion and peeling strength are used as evaluation indexes to carry out L ₉ (3 ⁴ ) And (4) performing orthogonal test. Factor levels are shown in the table below, and are statistically analyzed with a composite score = initial adhesion + holding adhesion + peel strength. The detailed results are shown in tables 9 to 11.

TABLE 9 orthogonal test horizontal factor table

TABLE 10 analysis of the levels of orthogonal tests and results

TABLE 11 results of ANOVA

The intuitive analysis of R values in a table shows that the four factors of ABCD have the influence on the forming of the gel emplastrum of C > A > D > B, A3> A1> A2, B1> B2> B3, C2> C1> C3 and D2> D1> D3, and the influence of C on the forming of the gel emplastrum is significant (F ratio > 1) from the analysis result of variance, which indicates that the factor C has influence on the matrix of the three-color dispersed gel emplastrum and has larger influence. A. The factors B and D (F is less than 1) have no significant difference, and the comprehensive visual analysis and scoring prompt that the factors A, B and D have certain influence on the three-color gel-dispersed plaster substrate, so that the optimal level combination of the factors A, B and D is proved to be A3, B3 and D1. Therefore, the optimal level combination of the factors is A3B 3C 2D 1, namely 58g of sodium polyacrylate, 330g of glycerol, 1.8g of dihydroxyaluminium aminoacetate and 2.5g of tartaric acid.

The invention provides a traditional Chinese medicine gel plaster for osteoarthritis anti-inflammatory and analgesic and a preparation method thereof, and a plurality of methods and ways for realizing the technical scheme are provided. All the components not specified in the present embodiment can be realized by the prior art.

Claims

1. A Chinese medicinal gel plaster for treating osteoarthritis and relieving inflammation and pain is characterized by comprising a back lining layer, a plaster layer and an anti-adhesion film; the plaster layer is a gel layer formed by the traditional Chinese medicine composition and a substrate for loading the traditional Chinese medicine composition;

the traditional Chinese medicine composition is prepared from the following components in parts by mass:

15 to 18 parts of chastetree fruit, 15 to 18 parts of Chinese redbud bark, 3 to 5 parts of Chinese angelica, 3 to 5 parts of pawpaw, 3 to 5 parts of salvia miltiorrhiza, 3 to 5 parts of red paeony root, 3 to 5 parts of angelica dahurica, 3 to 5 parts of rhizoma curcumae longae, 3 to 5 parts of radix angelicae pubescentis, 3 to 5 parts of notopterygium root, 3 to 5 parts of trichosanthes root, 3 to 5 parts of radix cyathulae, 3 to 5 parts of clematis root, 3 to 5 parts of radix stephaniae tetrandrae, 3 to 5 parts of radix sileris, 3 to 5 parts of nux vomica, 2 to 3 parts of ligusticum wallichii, 2 to 3 parts of gentiana macrophylla, 2 to 3 parts of fructus forsythiae and 1 to 2 parts of liquorice; the Chinese medicinal composition is obtained by extracting with 55% ethanol;

the matrix of the paste layer comprises glycerol, EDTA, dihydroxyaluminum, sodium polyacrylate, water, EM-178, AC-10H, a penetration enhancer, a preservative and tartaric acid;

the dosage of each component in the paste layer is as follows: glycerol, EDTA, dihydroxyaluminum glycolate, sodium polyacrylate, water, a traditional Chinese medicine composition, EM-178, AC-10H, a penetration enhancer, an antiseptic and tartaric acid = 330g, (0.5 to 1.5 g), (1.8 g), (58 g), (200 to 300g), (100 to 200g), (50 to 200g), (20 to 40g), (0.5 to 2ml) and (2.5 g).

2. The traditional Chinese medicine gel plaster for osteoarthritis anti-inflammatory and analgesic of claim 1, wherein the traditional Chinese medicine composition is prepared from the following components in parts by mass:

3. The Chinese medicinal gel patch for osteoarthritis anti-inflammatory and analgesic of claim 1, wherein the penetration enhancer is one or a mixture of two or more of menthol, camphor, borneol or azone.

4. The Chinese medicinal gel patch for osteoarthritis anti-inflammatory and analgesic of claim 1, wherein the backing layer is a non-woven fabric; the anti-sticking film is an embossed film with a viscose surface for gluing.

5. The method for preparing the traditional Chinese medicine gel plaster for osteoarthritis anti-inflammatory and analgesic as claimed in claim 1, is characterized by comprising the following steps:

s2: adding EM-178, AC-10H, penetration enhancer, antiseptic and Chinese medicinal composition into water, stirring and mixing to obtain phase B;

6. The use of the traditional Chinese medicine gel patch of claim 1 in the preparation of a medicament for treating osteoarthritis, inflammation and pain.