CN114209799A

CN114209799A - Traditional Chinese medicine composition for osteoarthritis anti-inflammatory and analgesic and gel emplastrum thereof

Info

Publication number: CN114209799A
Application number: CN202111585599.6A
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: 2021-12-22
Publication date: 2022-03-22
Also published as: CN115531505B; CN115531505A

Abstract

The invention discloses a traditional Chinese medicine composition for osteoarthritis anti-inflammatory analgesia and a gel emplastrum thereof, wherein 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 medicinal cyathula root, 3-5 parts of radix clematidis, 3-5 parts of radix stephaniae tetrandrae, 3-5 parts of divaricate saposhnikovia root, 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 anti-inflammatory analgesic gel emplastrum has the advantages that through the reasonable proportion of the matrix and the traditional Chinese medicine components, the obtained gel emplastrum is convenient to use, controllable in administration dosage, good in adhesion, continuous in effect, good in skin following performance, capable of providing reference for the reform of similar external preparation dosage forms, and convenient for clinical popularization and use.

Description

Traditional Chinese medicine composition for osteoarthritis anti-inflammatory and analgesic and gel emplastrum thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for osteoarthritis anti-inflammatory analgesia and gel plaster thereof.

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. Studies have shown 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.

Disclosure of Invention

The invention aims to solve the technical problem of providing an anti-inflammatory analgesic osteoarthritis formula, a gel emplastrum and a preparation method thereof aiming at the defects of the prior art, so that the effects of anti-inflammatory analgesic compatibility of traditional Chinese medicines and transdermal permeation promotion of the gel in vitro are exerted, and the clinical popularization and use are convenient.

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

a traditional Chinese medicine composition for osteoarthritis anti-inflammatory analgesia comprises the following components in parts by mass:

15-18 parts of fructus viticis, 15-18 parts of Chinese redbud bark, 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 curcumae longae, 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 divaricate saposhnikovia root, 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.

Preferably, the traditional Chinese medicine composition 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 cortex kadsurae chinensis as the monarch drugs, and has the effects of dissipating the cold and heat between bones, removing dampness, arthralgia and spasm, activating blood, stimulating the menstrual flow, reducing swelling and relieving 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 formula are processed to 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 according to the traditional maltose for a long time, so that 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.

Preferably, the anti-inflammatory analgesic osteoarthritis product can be prepared into different pharmaceutically acceptable dosage forms. Such as gel plaster, rubber plaster, gel, ointment, cream, paste, powder, etc.

Furthermore, the application of the traditional Chinese medicine composition in preparing the medicine for treating osteoarthritis is also in the protection scope of the invention.

Furthermore, the invention also provides an anti-inflammatory analgesic osteoarthritis gel emplastrum, which comprises a back lining layer, a plaster layer and an anti-adhesion film; the plaster layer comprises the traditional Chinese medicine composition and a substrate for loading the traditional Chinese medicine composition. 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 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.

Since the forming process of the formulation of the gel patch is more complicated than that of the matrix, the influence factor is 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 NL RP3 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 improving 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 10-25 wt.%.

Specifically, the mass ratio of each component in the paste layer is as follows: glycerin, EDTA, dihydroxyaluminum, sodium polyacrylate, water, Chinese medicinal composition powder, EM-178, AC-10H, a penetration enhancer, a preservative and tartaric acid, wherein the total weight of 250-400 g, (0.5-1.5 g), (1.0-3.0 g), (40-60 g), (200-300 g), (100-200 g), (50-200 g), (20-40 ml), (0.5-2 ml), (2.0-4.0 g), and preferably 330g, (0.9 g), (1.8 g), (58 g), (262.2 g), (150 g), (100 g), (30 g), (1 ml) and 2.5 g.

In the gel emplastrum for resisting inflammation and easing pain and osteoarthritis, sodium polyacrylate is used as a framework material, dihydroxyaluminum glycinate is used as a cross-linking agent, EM-178 and AC-10H are used as tackifiers, glycerin 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 ointment, and when the dosage is lower, the crosslinking degree of a matrix is lower, the whole body is loose, the viscosity is low, the ointment rigidity is poorer, the residual quantity is large, the ointment is easy to fall off, 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 the 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 gel emplastrum for resisting inflammation, easing pain and osteoarthritis 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, water is easily absorbed to form material lumps which are gel lumps and 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 the aluminum glyceroxide to the sodium polyacrylate to the EDTA to the glycerin is 1.0-3.0 g to 40-60 g to 0.5-1.5 g to 250-400 g, and most preferably 1.8g to 58g to 0.9g to 330 g.

Preferably, in the step S2, the dosage ratio of the EM-178, the AC-10H, the penetration enhancer, the preservative, the Chinese medicinal composition powder and the water is 100-200 g, 50-200 g, 20-40 g, 0.5-2.0 ml, 150g, 150-200 g; most preferably 150g:100g:30g:1ml:150g:200 g;

preferably, in step S3, the ratio of tartaric acid to water is 2.0-4.0 g:39.06g, and most preferably 2.5g:62.2 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.

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

the anti-inflammatory analgesic osteoarthritis prescription disclosed by the invention is scientifically compatible with the medicinal powders of fructus viticis, cortex cercis chinensis, angelica sinensis, pawpaw, salvia miltiorrhiza, red paeony root, angelica dahurica, rhizoma wenyujin concinnatae, radix angelicae pubescentis, notopterygium root, trichosanthes root, radix cyathulae, radix clematidis, radix stephaniae tetrandrae, radix sileris, nux vomica, ligusticum wallichii, gentiana macrophylla, fructus forsythiae and liquorice, and has the functions of promoting blood circulation, removing scars, relieving swelling and pain, dispelling wind-damp and benefiting joints; the gel plaster for resisting inflammation and easing pain developed based on the formula for resisting inflammation and easing pain has the advantages that the gel plaster obtained by reasonably proportioning the matrix and the traditional Chinese medicine components is convenient to use, controllable in administration dosage, good in adhesiveness, continuous in effect and good in skin following performance, solves the problems that a traditional Chinese medicine compound preparation for resisting inflammation and easing pain 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 dosage form reformation of similar external preparations, and facilitates 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: mixing the powder with maltose at a ratio of 1:4, stirring, coating on the back layer of the gasket, and administering about 1g per rat.

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

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

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

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

s4 mixing A, B, C phases, stirring under vacuum, coating on the back lining layer, and covering with anti-sticking film to obtain the final product.

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

Blank group: 10 healthy rats were taken.

Animal drug effect experiment of gel emplastrum

1. Experimental methods

(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 and hot plate apparatus at 55. + -. 0.5 ℃ respectively, and 5 rats per group were subjected to the experiment using the licked feet as an index of pain response. And its pain threshold was recorded.

(4) Results of the experiment

Table 2 and table 3 show the rat pain thresholds for the hot plate and cold plate methods, 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

The successfully molded 5 male SD rats were sacrificed by decapitation, the knee joints were cut after sterilization, and the synovial tissue was taken out and placed in a sterile phosphate buffer solution (PBS, pH 7.4) and washed 3 times repeatedly. Cutting the 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; filtering with 70 μm sieve, centrifuging at 1000r/min for 5min, suspending the precipitate in cell culture dish with DMEM medium containing 10% fetal calf serum and 1% penicillin-streptomycin double antibody, and culturing at 37 deg.C with 5% CO₂The 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

Detection was performed by ELISA. After each group of cells was cultured for 24h, the supernatants were collected, and the OD values of each group were measured at a wavelength of 450nm with a microplate reader and the IL-6, IL-1. beta. and TNF-. alpha. levels were calculated from the standard curves, strictly according to the instructions of the respective kit.

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 comparisons between groups were performed by one-way anova, and the comparisons between groups were performed by LS D test (alignment of variance) or Dunnett's T3 test (misalignment of variance). The test level α is 0.05.

The result of the detection

1. Grading of synovial inflammation in rats

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 group a; compared to group B, # P < 0.05; compared to group D, E, & P < 0.05; p <0.05 compared to group C;

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

The results are shown in FIG. 3: p <0.05 compared to group a; compared to group B, # P < 0.05; compared to group D, E, & P < 0.05.

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 per 1ml corresponding to 1g of the original medicinal material 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 60 g.

(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;

s4, mixing A, B, C, stirring uniformly in vacuum, coating 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 52 g.

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 400 g.

(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 300 g.

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

TABLE 6

Glycerol (g)	Initial adhesion	Adhesive force	Viscosity (Displacement)	Peel strength
					250	33	2311.67±470.06	0	0.460±0.023
300	37	2633±208.63	0	0.869±0.216
					350	41	1323±136.83	0	0.575±0.033
400	41	1370±95.72	4.33±1.53	0.792±0.093

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 3.5 g.

(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. From the results, it was found that when the amount of tartaric acid was 2.0g, the initial adhesion, adhesive strength, holding strength 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 2.0 g.

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 2.3 g.

(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 investigating the amount of aluminum glycollate are shown in Table 8.

TABLE 8

Dihydroxyaluminium (g)	Initial adhesion	Adhesive force	Viscosity (Displacement)	Peel strength
					1.0	33	2123.67±136.07	Falling off	0.877±0.065
1.5	38	2438.33±123.06	16.67±5.69	2.135±0.262
					1.8	39	3112±369.58	6.83±1.61	2.675±0.287
2.3	37	1576±102.50	3.33±0.58	0.324±0.023

Orthogonal design optimization prescription

Based on the previous literature research and single-factor experiment, sodium polyacrylate (A), glycerin (B), aluminum glycoxide (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 L₉(3⁴) And (4) performing orthogonal test. The factor levels are shown in the table below and are statistically analyzed on a composite score of 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

From the intuitive analysis of R values in the table, the influence of four factors of ABCD on the gel emplastrum forming is C > A > D > B, A3> A1> A2, B1> B2> B3, C2> C1> C3, D2> D1> D3, and from the analysis result of variance, the influence of C on the gel emplastrum forming is significant (F ratio >1), which indicates that the factor C has influence on the three-color dispersed gel emplastrum matrix and has larger influence. A. B, D factors (F ratio is less than 1) have no significant difference, and then comprehensive visual analysis and scoring are carried out, so that the A, B, D factors are prompted to have certain influence on the three-color gel-dispersed plaster substrate, and the optimal level combination of nine A, B, D factors is proved to be A3, B3 and D1. Therefore, the optimal level combination of all 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 Chinese medicinal composition for treating osteoarthritis, inflammation and pain, and a gel emplastrum thereof, and a method and a device for realizing the technical scheme are numerous, the above description is only a preferred embodiment of the invention, and it should be noted that, for a person skilled in the art, a plurality of improvements and decorations can be made without departing from the principle of the invention, and the improvements and decorations should be regarded as the protection scope of the invention. All the components not specified in the present embodiment can be realized by the prior art.

Claims

1. The traditional Chinese medicine composition for osteoarthritis anti-inflammatory analgesia is characterized by comprising the following components in parts by mass:

2. The traditional Chinese medicine composition for osteoarthritis anti-inflammatory pain relief according to claim 1, is characterized by comprising the following components in parts by mass:

3. Use of a Chinese medicinal composition according to claim 1 or 2 in the manufacture of a medicament for the treatment of osteoarthritis.

4. An anti-inflammatory analgesic osteoarthritis gel emplastrum is characterized by comprising a back lining layer, a plaster layer and an anti-adhesion film; the plaster layer comprises the traditional Chinese medicine composition of claim 1 and a substrate for loading the traditional Chinese medicine composition; the back lining layer is non-woven fabric; the anti-sticking film is an embossed film with a viscose surface coated with glue;

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

5. The anti-inflammatory analgesic osteoarthritis gel emplastrum as claimed in claim 4, wherein in the plaster layer, the traditional Chinese medicine composition is water extract, alcohol extract, volatile oil, mixed plaster preparation or medicine powder thereof, and the medicine loading rate is 10-25 wt.%.

6. The anti-inflammatory analgesic osteoarthritis gel emplastrum as claimed in claim 4, wherein the mass ratio of each component in the plaster layer is as follows: glycerin, EDTA, dihydroxyaluminum, sodium polyacrylate, water, Chinese medicinal composition powder, EM-178, AC-10H, a penetration enhancer, a preservative and tartaric acid, wherein the weight percentage of 250-400 g (0.5-1.5 g) and the weight percentage of 1.0-3.0 g (40-60 g) and the weight percentage of 200-300 g are respectively 150g (100-200 g) and the weight percentage of 50-200 g (20-40 ml) and the weight percentage of 0.5-2 ml (2.0-4.0 g).

7. The gel patch for anti-inflammatory and analgesic osteoarthritis as claimed in claim 6, wherein the penetration enhancer is one or a mixture of two or more of menthol, camphor, borneol or azone.

8. The method for preparing the gel emplastrum for anti-inflammatory analgesic osteoarthritis of claim 6, which comprises 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;

9. The method for preparing an anti-inflammatory analgesic osteoarthritis gel emplastrum according to claim 8, wherein in step S2, the dosage ratio of EM-178, AC-10H, penetration enhancer, preservative, traditional Chinese medicine composition powder to water is 100-200 g: 50-200 g: 20-40 ml: 0.5-2 ml: 150-200 g.

10. The method for preparing an anti-inflammatory analgesic osteoarthritis gel emplastrum according to claim 8, wherein in step S3, the ratio of tartaric acid to water is 2.0-4.0 g: 50.0-100.0 g.