Preparation method of traditional Chinese medicine compound bone and bone cataplasm and related products thereof

Abstract

The invention relates to a traditional Chinese medicine compound bone and bone cataplasm preparation method and related products thereof, and belongs to the field of traditional Chinese medicine preparations. The preparation method comprises the following steps: 1) preparing volatile oil; 2) preparing an alcohol extract; (3) preparing a water extract; and (4) preparing the cataplasm. The invention also provides a related product obtained by the preparation method and related application of the product.

Description

Technical Field

[0001] The present invention relates to a preparation method of a traditional Chinese medicine compound tendon and bone cataplasm and related products, belonging to the field of traditional Chinese medicine preparations. Background Art

[0002] Wantong Jin Gu Tablets is a traditional Chinese medicine widely used in diseases such as rheumatic bone pain, arthritis, and traumatic injuries. It has the effects of promoting blood circulation to remove blood stasis, dispelling wind and dampness, and dredging collaterals to relieve pain. This medicine usually adopts the dosage form of oral tablets and is deeply favored by patients due to its good clinical efficacy. However, the oral dosage form has certain limitations. For example, the metabolic effect of the drug in the gastrointestinal tract may lead to the degradation or loss of some active ingredients, thereby affecting the drug effect. At the same time, long-term oral administration may cause certain irritation to the gastrointestinal tract and trigger adverse reactions. Therefore, how to optimize the administration method of Wantong Jin Gu Tablets to improve the bioavailability of the drug and reduce side effects has become an urgent problem to be solved by those skilled in the art.

[0003] In recent years, transdermal drug delivery technology has developed rapidly and shown broad application prospects in the treatment field of osteoarticular diseases. Transdermal drug delivery can not only avoid the first-pass effect of the drug and increase the local drug concentration, but also has the advantages of convenient use and reduced gastrointestinal irritation. As a form of transdermal drug delivery, cataplasm has good adhesiveness and permeability, can form a persistent drug reservoir on the skin surface, and enables the drug to be slowly released and penetrate through the skin directly to the affected area, thereby achieving long-acting analgesic and anti-inflammatory effects.

[0004] Chinese Patent CN101559128A discloses an external cataplasm developed based on Wantong Jin Gu Tablets. It separately extracts volatile oil, alcohol extract, water extract, etc., uses sodium polyacrylate, carbomer, gelatin for capsules, peach gum, glycerin, sodium hydroxide, and purified water as the matrix, and azone and propylene glycol as penetration enhancers; obtains a cataplasm; and makes a preliminary attempt on the external dosage form of Wantong Jin Gu Tablets. Summary of the Invention

[0005] The first aspect of the present invention is to provide a preparation method of a traditional Chinese medicine tendon and bone cataplasm, which includes:

[0006] 1) Preparation of volatile oil: Notopterygium incisum, Asarum sieboldii, Myrrha (processed), Cinnamomum cassia, Panax ginseng, Acanthopanax senticosus, Pilose antler are first soaked for 2 hours, and then the volatile oil is extracted by steam distillation. The volatile oil and the medicinal liquid are stored separately in another container;

[0007] 2) Preparation of ethanol extract: The medicinal residues obtained from preparing the volatile oil, together with 10 herbs such as Radix Dipsaci, Rhizoma Drynariae Praeparatum, Radix Aconiti Praeparata, Radix Aconiti Kusnezoffii Praeparata, Semen Strychni Praeparatum, Cortex Phellodendri Chinensis, Dryopteris Crassirhizoma, Cortex Illicii Diffusae, Pheretima, and Herba Taxilli, are extracted with 70% ethanol 3 times. The ethanol addition amount is 6 times each time, and the extraction time is 1.5 hours each time. Filter out the ethanol extract, recover ethanol, and concentrate it under reduced pressure to an extract with a relative density of 1.28 - 1.30 (50 °C) for storage in another container;

[0008] 3) Preparation of water extract: Epimedium, Glycyrrhiza, Achyranthes bidentata, Lonicera japonica, Prunus mume, Ephedra, Carthamus tinctorius, Zaocys dhumnades are added with 8 times water and extracted 3 times, with each extraction time being 1.5 hours; The medicinal liquid is combined with the medicinal liquid of the herbs for extracting volatile oil, concentrated under reduced pressure to a relative density of 1.045 - 1.065 (50 °C), centrifuged to remove impurities, and the supernatant is concentrated under reduced pressure to a relative density of 1.28 - 1.30 (50 °C) for standby of the extract;

[0009] 4) Preparation of cataplasm: Combine the water extract paste and the ethanol extract paste, weigh the matrix materials to make the matrix, add volatile oil, laurocapram, propylene glycol, propylparaben, ethylparaben, disodium edetate, and the traditional Chinese medicine extract paste, stir and mix, coat, slice, and package.

[0010] In one embodiment, the matrix materials include: sodium polyacrylate, carbomer, gelatin, sodium alginate, peach gum, glycerol, sodium hydroxide, and purified water. The weight ratio of sodium polyacrylate, carbomer, gelatin, sodium alginate, peach gum, glycerol, sodium hydroxide, and purified water is 3.6:4:6:1 - 12:9:30:1.5:40.

[0011] In another embodiment, the weight ratio of the water extract paste, the ethanol extract paste, and the matrix materials is 1:10 - 30, preferably 1:20.

[0012] In another embodiment, the weight ratio of gelatin and sodium alginate is 1:0.1 - 1; preferably 1:0.5.

[0013] In another embodiment, the dosages of the medicinal materials are as follows: prepared Radix Aconiti Lateralis Preparata 7 - 23 parts by weight, prepared Radix Aconiti Kusnezoffii 7 - 23 parts by weight, prepared Semen Strychni 7 - 23 parts by weight, Epimedii Herba 7 - 23 parts by weight, Achyranthis Bidentatae Radix 7 - 23 parts by weight, Notopterygii Rhizoma 7 - 23 parts by weight, Dryopteridis Crassirhizomatis Rhizoma 7 - 23 parts by weight, Phellodendri Chinensis Cortex 7 - 23 parts by weight, Zaocys 7 - 23 parts by weight, Cornu Cervi Pantotrichum 4 - 16 parts by weight, Dipsaci Radix 7 - 23 parts by weight, Mume Fructus 7 - 23 parts by weight, Asari Radix et Rhizoma 2 - 10 parts by weight, Ephedrae Herba 7 - 23 parts by weight, Cinnamomi Ramulus 7 - 23 parts by weight, Carthami Flos 7 - 23 parts by weight, Acanthopanacis Senticosi Radix 7 - 23 parts by weight, Lonicerae Japonicae Flos 7 - 23 parts by weight, Pheretima 7 - 23 parts by weight, Taxilli Herba 7 - 23 parts by weight, Glycyrrhizae Radix et Rhizoma 7 - 23 parts by weight, Rhizoma Drynariae Praeparatum 7 - 23 parts by weight, Illicii Cortex 7 - 23 parts by weight, Myrrha Praeparata 7 - 23 parts by weight, Ginseng Rubra 7 - 23 parts by weight.

[0014] The second aspect of the present invention is to provide a preparation method of a traditional Chinese medicine tendon and bone cataplasm, which includes:

[0015] 1) Preparation of volatile oil: Notopterygii Rhizoma, Asari Radix et Rhizoma, Myrrha Praeparata, Cinnamomi Ramulus, Ginseng Rubra, Acanthopanacis Senticosi Radix, and Cornu Cervi Pantotrichum are first soaked for 2 hours, and then the volatile oil is extracted by steam distillation. The volatile oil and the medicinal liquid are stored separately in another container;

[0016] 2) Preparation of alcohol extract: The medicinal residues obtained from preparing the volatile oil and 10 medicinal materials such as Dipsaci Radix, Rhizoma Drynariae Praeparatum, prepared Radix Aconiti Lateralis Preparata, prepared Radix Aconiti Kusnezoffii, prepared Semen Strychni, Phellodendri Chinensis Cortex, Dryopteridis Crassirhizomatis Rhizoma, Illicii Cortex, Pheretima, and Taxilli Herba are extracted 3 times with 70% ethanol. The amount of added ethanol is 6 times each time, and the extraction time is 1.5 hours each time; The alcohol extract is filtered out, the ethanol is recovered, and it is concentrated under reduced pressure to an extract with a relative density of 1.28 - 1.30 (50 °C) and stored separately in another container;

[0017] 3) Preparation of the microemulsion sample: The obtained volatile oil is mixed with a co - surfactant and stirred evenly to form an oil phase; Under the condition of 35 °C, a surfactant is gradually added to the oil phase and stirred evenly to form a primary emulsion; Under the action of a high - shear emulsifier at 10000 rpm, all the obtained alcohol extract is gradually added; It is treated with ultrasonic waves at a frequency of 20 kHz for 20 min to form a stable microemulsion;

[0018] 4) Preparation of water extract: Epimedii Herba, Glycyrrhizae Radix et Rhizoma, Achyranthis Bidentatae Radix, Lonicerae Japonicae Flos, Mume Fructus, Ephedrae Herba, Carthami Flos, and Zaocys are added with 8 times water and extracted 3 times, with each extraction time being 1.5 hours. The medicinal liquid is combined with the medicinal liquid of the medicinal materials for extracting the volatile oil, concentrated under reduced pressure to a relative density of 1.045 - 1.065 (50 °C), centrifuged to remove impurities, and the supernatant is concentrated under reduced pressure to a relative density of 1.28 - 1.30 (50 °C), and the extract is reserved for use;

[0019] 5) Preparation of cataplasm: Combine the water extract paste with the microemulsion. Weigh sodium polyacrylate, carbomer homopolymer, gelatin for capsules, sodium alginate, peach gum, glycerol, sodium hydroxide, and purify them to prepare the matrix, propylene glycol, propylparaben, ethylparaben, disodium edetate, and Chinese medicine extract paste. Stir and mix, coat, slice, and package.

[0020] In one embodiment, the co-surfactant is selected from propylene glycol or ethanol, and the volume-to-weight ratio of the co-surfactant to the volatile oil is 1 g: 0.5 - 2 ml, preferably 1 g: 1.3 ml.

[0021] In one embodiment, the surfactant is one or more of Tween 80, lecithin, and Span 80, preferably Tween 80. The volume-to-weight ratio of the surfactant to the volatile oil is 1 g: 2 - 6 ml, preferably 1 g: 4 ml.

[0022] The third aspect of the present invention is to provide a cataplasm obtained by the above preparation method.

[0023] The fourth aspect of the present invention is to provide the application of the cataplasm in the preparation of analgesic drugs.

[0024] By optimizing the known cataplasm matrix, the present invention solves the problem of asynchronous transdermal efficiency of alkaloid components and saponin components in the original cataplasm; and through the microemulsification treatment of volatile oil and alcohol extract, it is unexpectedly found that the transdermal absorption rate of saponin components can be greatly improved, and without adding laurocapram in the original prescription ketone, while improving the effect of the cataplasm, it also removes the skin irritation caused by laurocapram ketone. Detailed implementation manners

[0025] The following further elaborates on the present application with reference to the embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative efforts belong to the scope of protection of the present invention.

[0026] Preparation of Compound Jin Gu Cataplasm for Proportion Example 1

[0027] Radix Aconiti Lateralis Preparata 67.48 g, Radix Aconiti Kusnezoffii Preparata 67.48 g, Semen Strychni Preparata 67.48 g, Herba Epimedii 90.16 g, Radix Achyranthis Bidentatae 67.48 g, Rhizoma seu Radix Notopterygii 67.48 g, Dryopteris Crassirhizoma 90.16 g, Cortex Phellodendri Amurensis 67.48 g, Zaocys dhumnades 67.48 g, Cornu Cervi Pantotrichum 45.08 g, Radix Dipsaci 67.48 g, Fructus Mume 67.48 g, Herba Asari 33.81 g, Herba Ephedrae 67.48 g, Ramulus Cinnamomi 67.48 g, Flos Carthami 67.48 g, Radix Acanthopanacis Senticosi 67.48 g, Flos Lonicerae Japonicae 67.48 g, Pheretima 67.48 g, Herba Taxilli 67.48 g, Radix Glycyrrhizae 67.48 g, Rhizoma Drynariae Praeparata 67.48 g, Cortex Illicii 67.48 g, Myrrha Praeparata 67.48 g, Radix Ginseng Rubra 67.48 g

[0028] Preparation of volatile oil: First, Notopterygium root, Asarum herb, prepared Myrrh, Cinnamon twig, Red Ginseng, Acanthopanax senticosus, and Pilose Antler are soaked for 2 hours, and then the volatile oil is extracted by steam distillation. The volatile oil (3.93 ml) and the medicinal liquid are stored separately in another container;

[0029] Preparation of ethanol extract: The medicinal residues obtained from the preparation of volatile oil, together with 10 herbs such as Dipsacus root, Drynaria rhizome, Prepared Aconite Root, Prepared Kusnezoff Monkshood Root, Prepared Nux Vomica Seed, Amur Corktree Bark, Dryopteris Crassirhizoma, Cortex Illicii, Earthworm, and Taxillus Herb, are extracted 3 times with 70% ethanol. The amount of added ethanol is 6 times each time, and the extraction time is 1.5 hours each time. The ethanol extract is filtered out, the ethanol is recovered, and it is concentrated under reduced pressure to a relative density of 1.28 - 1.30 (50 °C), and the extract is stored separately in another container.

[0030] Preparation of water extract: Herba Epimedii, Licorice root, Achyranthes root, Honeysuckle flower, Fructus Mume, Ephedra herb, Safflower flower, Zaocys dhumnades are added with 8 times water and extracted 3 times, with each extraction time being 1.5 hours. The medicinal liquid is combined with the medicinal liquid of the herbs for extracting volatile oil, concentrated under reduced pressure to a relative density of 1.045 - 1.065 (50 °C), centrifuged to remove impurities, and the supernatant is concentrated under reduced pressure to a relative density of 1.28 - 1.30 (50 °C), and the extract is reserved for use;

[0031] Preparation of cataplasm: The water extract paste and the ethanol extract paste are combined (a total of 333.2 g). Weigh polyacrylate sodium, carbomer homopolymer, gelatin for capsules, peach gum, glycerol, sodium hydroxide, and purified water (weight ratio: 3.6:4.0:6.0:9.0:30:1.5:40), a total of 6585 g, to make a matrix. Add volatile oil, laurylazacycloheptanone ketone, propylene glycol, 7 g each, propylparaben and ethylparaben, 0.35 g each, disodium edetate 0.14 g, and the traditional Chinese medicine extract paste, stir and mix, coat and slice to make 1000 patches and package.

[0032] Matrix Optimization of Compound Jin Gu Cataplasm for Test Example 1

[0033] Since the traditional Chinese medicine compound of the present invention is an external preparation of Wantong Jinhu Tablets, a large number of medicinal materials in it contain alkaloid components, which are also one of the main active components of this compound. In the oral application of Wantong Jinhu Tablets, due to the need for gastrointestinal absorption and metabolism and the first-pass effect of the liver, the toxicity of the alkaloid components in this compound will be reduced (for example, the aconitine components in Radix Aconiti Lateralis Preparata and Radix Aconiti Kusnezoffii Preparata). However, for external preparations, without the first-pass effect and directly absorbed into the blood, the toxicity problem of excessive accumulation of alkaloid components in a short time needs to be considered. Therefore, carbomer homopolymer was added in the matrix formulation design of Comparative Example 1 to play a controlled-release role.

[0034] However, the present invention found in the research that although the carbomer homopolymer played a certain controlled-release role in the formulation of Comparative Example 1, due to the presence of penetration enhancers such as laurocapram and propylene glycol, its controlled-release effect was not good; in addition, the percutaneous penetration rate of saponin components in the cataplasm prepared in Comparative Example 1 was not good, significantly lower than that of alkaloid components. In the traditional Chinese medicine compound design system of the present invention, saponin components not only play a therapeutic role, but also have the effect of alleviating the toxicity of alkaloid components. Therefore, how to control the percutaneous penetration rates of alkaloid components and saponin components in the traditional Chinese medicine compound is an important inventive point of the present invention.

[0035] Test method:

[0036] 1) Preparation of cataplasm samples

[0037] Group 1: Replace the carbomer homopolymer in Comparative Example 1 with an equal amount of diatomaceous earth;

[0038] Group 2: Replace the carbomer homopolymer in Comparative Example 1 with an equal amount of hypromellose;

[0039] Group 3: Replace the capsule gelatin in Comparative Example 1 with an equal amount of chitosan;

[0040] Group 4: Add sodium alginate to the matrix formulation of Comparative Example 1, with the same dosage as gelatin;

[0041] Group 5: Add AlCl 3 , with the same dosage as sodium hydroxide;

[0042] The preparation methods of the above 5 groups of cataplasm samples are the same as those in Comparative Example 1.

[0043] 2) Investigation of in vitro percutaneous absorption of each group of cataplasm samples

[0044] Preparation of ex vivo mouse skin: Kunming male mice weighing about 20 g were selected, the hair on the abdominal and back skin was shaved off, and the mice were sacrificed. The skin was cut off, and the subcutaneous tissue was gently scraped off with a cotton swab until the skin was smooth and translucent on the surface. It was repeatedly washed with distilled water and then rinsed with physiological saline before use.

[0045] Ex vivo percutaneous experiment: The experimental device was a vertical Franz diffusion cell, and 0.9% physiological saline was used as the absorption solution. During the experiment, the prepared cataplasm sample was closely attached to the stratum corneum of the mouse skin, the air bubbles between the cataplasm and the skin were excluded, and then it was fixed between the diffusion chamber and the receiving chamber with a clip. A magnetic stir bar was placed in the receiving chamber, filled with the absorption solution, and the air bubbles were excluded. The magnetic stirring speed was set at 200 rpm, and the water bath temperature was controlled at 37 °C. The volume of the receiving chamber was 15 ml, and the effective contact area was 2.39 cm 2 . The release test was carried out in the same way using a porous membrane instead of the mouse skin.

[0046] At 12 h and 24 h respectively, all the absorption solution in the receiving chamber was poured out, and at the same time, fresh absorption solution preheated to 37 °C was added. After the sampled absorption solution was evaporated to dryness in a water bath, the residue was dissolved in acetonitrile, and the concentrations of mesaconitine and ginsenoside Rg1 were detected by HPLC, and the percutaneous penetration amount of the drug was calculated.

[0047] HPLC conditions: Octadecylsilane chemically bonded silica was used as the filler; a mobile phase of acetonitrile - an equal - volume mixture of 0.01 mol / L sodium heptanesulfonate and 0.02 mol / L potassium dihydrogen phosphate (adjusted to pH 2.8 with 10% phosphoric acid) (21∶79) was used. Detection was carried out using a UV detector, and the detection wavelength was 210 nm.

[0048] The cumulative penetration amount Q (μg / cm 2 ) can be calculated according to the following formula.

[0049]

[0050] Where Ci is the concentration of the drug measured in the i - th sampling (μg·ml); A is the penetration area (cm 2 ); Vi is the sampling volume (ml). The cumulative penetration amount Q of the drug through the mouse skin was calculated from this formula 药 drug.

[0051] Furthermore, the percutaneous permeability rate P of the drug can be calculated according to the following formula: P = Q 药物 / Q 巴布膏剂 . Where Q 巴布膏剂 is the drug content in the cataplasm per unit area.

[0052] The specific results are as follows:

[0053] The cumulative permeation amounts and percutaneous permeation rates of mesaconitine and ginsenoside Rg1 in each cataplasm sample at 24 h.

[0054]

[0055] As can be seen from the above table, replacing carbomer with diatomaceous earth or hypromellose (Groups 1 and 2) does not affect the permeation rate of mesaconitine, but the permeation rate of ginsenoside Rg1 is not improved compared with that of Comparative Example 1, and even slightly lower than that of Comparative Example 1. Replacing gelatin with chitosan (Group 3) can improve the permeation rate of ginsenoside Rg1. And adding the cross-linking agent AlCl 3 (Group 5) has the worst effect, and the permeation rates of alkaloid and saponin components both show a significant decrease. The permeation rates of alkaloid and saponin components in Group 4 are the best, especially the permeation rate of ginsenoside Rg1 shows a significant increase, which may be related to the composite hydrogel system of alginic acid and gelatin. Therefore, the matrix systems of Group 3 and Group 4 are beneficial to the subsequent research and development of compound cataplasm.

[0056] Investigation on the Dosage of Sodium Alginate in Compound Jin Gu Cataplasm for Test Example 2

[0057] According to the scheme of Group 4 in Test Example 1, further investigate the optimal dosage of sodium alginate.

[0058] Test method: The same as Test Example 1, the difference is that the dosage of sodium alginate added is different, specifically as follows:

[0059] Group 1: The weight ratio of sodium alginate to gelatin is 1:2;

[0060] Group 2: The weight ratio of sodium alginate to gelatin is 2:1;

[0061] The specific results are as follows:

[0062]

[0063] As can be seen from the above results and combined with the relevant data of Test Example 1, from the perspective of the permeation rates of alkaloid and saponin components, when the weight ratio of sodium alginate to gelatin is 1:2, the permeation rates of the two components are the best.

[0064] Effect of Emulsification of Volatile Oil and Compound Alcohol Extract on Transdermal Absorption of Active Ingredients for Test Example 3

[0065] In the cataplasm, in addition to its therapeutic effect, volatile oil also has a certain effect of promoting the transdermal absorption of other active ingredients. However, in the investigation of Comparative Example 1 of the present invention, it is found that this effect is not obvious. Therefore, it is necessary to consider further exerting the role of volatile oil in the traditional Chinese medicine cataplasm for strengthening muscles and bones.

[0066] Test method:

[0067] 1) Preparation of microemulsion sample: Mix all the volatile oils obtained in Comparative Example 1 with a co-surfactant (propylene glycol). The amount of propylene glycol used is 3 g. Stir evenly to form an oil phase. At 35 °C, gradually add a surfactant to the oil phase and stir evenly to form a primary emulsion. Under the action of a high-shear emulsifier (10,000 rpm), gradually add all the alcohol extracts obtained in Comparative Example 1. Treat with ultrasound at a frequency of 20 kHz for 20 min to form a stable microemulsion.

[0068] The amounts of surfactant used are as follows:

[0069] Group 1: Tween 80, amount used 1 g;

[0070] Group 2: Soybean lecithin, amount used 1 g;

[0071] Group 3: Tween 80, amount used 0.5 g; Soybean lecithin, amount used 0.5 g;

[0072] 2) Preparation of cataplasm sample:

[0073] Combine the water extract paste in Comparative Example 1 with the microemulsion sample. Weigh a total of 6585 g of sodium polyacrylate, carbomer homopolymer, gelatin for capsules, sodium alginate, peach gum, glycerol, sodium hydroxide, and purified water (weight ratio: 3.6:4.0:6.0:3.0:9.0:30:1.5:40) to make a matrix. Add 4 g of propylene glycol, 0.35 g each of propylparaben and ethylparaben, 0.14 g of disodium edetate, and the traditional Chinese medicine extract paste. Stir and mix, coat and slice to make 1000 patches and package.

[0074] 3) Investigation of in vitro transdermal absorption of each cataplasm sample: The same as Test Example 1.

[0075] The specific results are as follows:

[0076]

[0077] In previous preliminary experiments, it was found that when surfactants Tween 80, polyoxyl castor oil, Span 80, and soybean lecithin (all added 1 g) were added alone to microemulsify the volatile oils and alcohol extracts, and the stability of the obtained samples was investigated at room temperature for 24 hours, the effects of Tween 80 and soybean lecithin were the best. Therefore, on the basis of the preliminary experiments, the present invention uses Tween 80, soybean lecithin, and their mixtures added alone for microemulsification and the subsequent preparation of cataplasms.

[0078] As can be seen from the results in the above table, in terms of the permeation rates of mesaconitine and ginsenoside Rg1, the microemulsification process with the sole addition of Tween 80 can significantly improve the permeation rate of mesaconitine. Particularly unexpectedly, the microemulsification combination test example 1 of the volatile oil and the alcohol extract, with the matrix prescription, can greatly improve the permeation rate of saponin components, and this effect is achieved by removing the penetration enhancer laurocapram from the matrix prescription.

[0079] However, the microemulsified cataplasm sample (group 3) with the mixture of Tween 80 and soybean lecithin not only fails to increase the permeation rate but instead slightly decreases it. No obvious effect was found in the microemulsified cataplasm sample (group 2) of soybean lecithin. This may be related to the removal of laurocapram from the excipient prescription, thus reducing part of the penetration enhancement. Since the preparation process of cataplasm is relatively complex and the components of traditional Chinese medicine compound are also relatively complex, the specific mechanism remains to be further studied.

[0080] Example 1: Preparation of Traditional Chinese Medicine Jin Gu Cataplasm

[0081] 67.48 g of Radix Aconiti Preparata, 67.48 g of Radix Aconiti Kusnezoffii Preparata, 67.48 g of Semen Strychni Preparata, 90.16 g of Herba Epimedii, 67.48 g of Radix Achyranthis Bidentatae, 67.48 g of Rhizoma seu Radix Notopterygii, 90.16 g of Dryopteris Crassirhizoma, 67.48 g of Cortex Phellodendri Chinensis, 67.48 g of Zaocys, 45.08 g of Cornu Cervi Pantotrichum, 67.48 g of Radix Dipsaci, 67.48 g of Fructus Mume, 33.81 g of Herba Asari, 67.48 g of Herba Ephedrae, 67.48 g of Ramulus Cinnamomi, 67.48 g of Flos Carthami, 67.48 g of Radix Acanthopanacis Senticosus, 67.48 g of Flos Lonicerae Japonicae, 67.48 g of Pheretima, 67.48 g of Herba Taxilli, 67.48 g of Radix Glycyrrhizae, 67.48 g of Rhizoma Drynariae Praeparata, 67.48 g of Cortex Illicii, 67.48 g of Myrrha Praeparata, 67.48 g of Radix Ginseng Rubra

[0082] Preparation of volatile oil: Herba Notopterygii, Herba Asari, Myrrha Praeparata, Ramulus Cinnamomi, Radix Ginseng Rubra, Radix Acanthopanacis Senticosus, and Cornu Cervi Pantotrichum are first soaked for 2 hours and then distilled with steam to extract the volatile oil. The volatile oil and the medicinal liquid are stored separately in different containers;

[0083] Preparation of alcohol extract: The medicinal residues obtained from preparing the volatile oil, together with 10 herbs such as Radix Dipsaci, Rhizoma Drynariae Praeparata, Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Semen Strychni Preparata, Cortex Phellodendri Chinensis, Dryopteris Crassirhizoma, Cortex Illicii, Pheretima, and Herba Taxilli, are extracted 3 times with 70% ethanol. The amount of added alcohol is 6 times each time, and the extraction time is 1.5 hours each time. The alcohol extract is filtered out, the ethanol is recovered, and it is concentrated under reduced pressure to a relative density of 1.28 - 1.30 (50 °C), and the extract is stored separately in a different container.

[0084] Preparation of aqueous extract: Epimedium, Licorice Root, Achyranthes bidentata, Honeysuckle Flower, Dark Plum, Ephedra, Safflower, Zaocys dhumnades were added with 8 times of water and extracted 3 times, with each extraction lasting for 1.5 hours. The medicinal liquid was combined with the medicinal liquid of the herbs for extracting volatile oil, and concentrated under reduced pressure to a relative density of 1.045 - 1.065 (50 °C), centrifuged to remove impurities, and the supernatant was further concentrated under reduced pressure to a relative density of 1.28 - 1.30 (50 °C), and the extract was reserved for use;

[0085] Preparation of cataplasm: The aqueous extract and the ethanol extract were combined. Weighed polyacrylate sodium, carbomer homopolymer, gelatin for capsules, sodium alginate, peach gum, glycerol, sodium hydroxide, purified water (weight ratio: 3.6:4.0:6.0:3.0:9.0:30:1.5:40) totaling 6585 g were made into a matrix, volatile oil was added, and laurocapram 7 g each of ketone and propylene glycol, 0.35 g each of propylparaben and ethylparaben, 0.14 g of disodium edetate, and the Chinese medicine extract were stirred and mixed, coated and sliced to make 1000 patches for packaging.

[0086] Example 2: Preparation of Traditional Chinese Medicine Jin Gu Cataplasm

[0087] 67.48 g of Radix Aconiti Preparata, 67.48 g of Radix Aconiti Kusnezoffii Preparata, 67.48 g of Semen Strychni Preparata, 90.16 g of Epimedium, 67.48 g of Achyranthes bidentata, 67.48 g of Notopterygium incisum, 90.16 g of Dryopteris crassirhizoma, 67.48 g of Phellodendron amurense, 67.48 g of Zaocys dhumnades, 45.08 g of Cornu Cervi Pantotrichum, 67.48 g of Dipsacus asperoides, 67.48 g of Dark Plum, 33.81 g of Asarum, 67.48 g of Ephedra, 67.48 g of Ramulus Cinnamomi, 67.48 g of Safflower, 67.48 g of Acanthopanax senticosus, 67.48 g of Honeysuckle Flower, 67.48 g of Pheretima aspergillum, 67.48 g of Taxillus chinensis, 67.48 g of Licorice Root, 67.48 g of Drynaria fortunei, 67.48 g of Cortex Illicii, 67.48 g of Myrrha (processed), 67.48 g of Radix Ginseng Rubra

[0088] Preparation of volatile oil: Notopterygium incisum, Asarum, Myrrha (processed), Ramulus Cinnamomi, Radix Ginseng Rubra, Acanthopanax senticosus, Cornu Cervi Pantotrichum were first soaked for 2 hours, and then the volatile oil was extracted by steam distillation. The volatile oil and the medicinal liquid were stored separately;

[0089] Preparation of ethanol extract: The medicinal residues obtained from preparing the volatile oil were extracted 3 times with 70% ethanol together with 10 herbs including Dipsacus asperoides, Drynaria fortunei, Radix Aconiti Preparata, Radix Aconiti Kusnezoffii Preparata, Semen Strychni Preparata, Phellodendron amurense, Dryopteris crassirhizoma, Cortex Illicii, Pheretima aspergillum, Taxillus chinensis. The amount of ethanol added was 6 times each time, and the extraction time was 1.5 hours each time. The ethanol extract was filtered out, the ethanol was recovered, and concentrated under reduced pressure to a relative density of 1.28 - 1.30 (50 °C), and the extract was stored separately.

[0090] Preparation of microemulsion sample: The obtained volatile oil was mixed with a co-surfactant (propylene glycol) in an amount of 3 g, and stirred evenly to form an oil phase. At 35 °C, the surfactant (Tween 80, 1 g) was gradually added to the oil phase and stirred evenly to form a primary emulsion. Under the action of a high-shear emulsifier (10,000 rpm), all the obtained ethanol extracts were gradually added. Ultrasonic treatment was carried out at a frequency of 20 kHz for 20 min to form a stable microemulsion.

[0091] Preparation of water extract: Epimedium, Glycyrrhiza uralensis, Achyranthes bidentata, Lonicera japonica, Prunus mume, Ephedra sinica, Carthamus tinctorius, Zaocys dhumnades were added with 8 times of water and extracted 3 times, each extraction for 1.5 hours. The medicinal liquid was combined with the medicinal liquid for extracting volatile oil, concentrated under reduced pressure to a relative density of 1.045 - 1.065 (50 °C), centrifuged to remove impurities, and the supernatant was concentrated under reduced pressure to a relative density of 1.28 - 1.30 (50 °C), and the extract was reserved for use.

[0092] Preparation of cataplasm: The water extract paste was combined with the microemulsion. Weigh sodium polyacrylate, carbomer homopolymer, gelatin for capsules, sodium alginate, peach gum, glycerol, sodium hydroxide, purified water (weight ratio: 3.6:4.0:6.0:3.0:9.0:30:1.5:40) totaling 6585 g to make a matrix, 4 g of propylene glycol, 0.35 g each of propylparaben and ethylparaben, 0.14 g of disodium edetate, and the Chinese medicine extract, stirred and mixed, coated and sliced to make 1000 patches and packaged.

Claims

1. A method for preparing a traditional Chinese medicine muscle and bone paste, comprising: 1) Preparation of volatile oil: soak the seven herbs of Notopterygium wilfordii, Asarum, Myrrha (processed), Cinnamon twig, Red ginseng, Acanthopanax senticosus, and Pilose antler for 2 hours, then extract the volatile oil by steam distillation, and store the volatile oil and the medicinal solution in separate containers; 2) Preparation of alcohol extract: extract the residue obtained from the preparation of volatile oil with 10 medicinal materials including Radix Dipsaci, Rhizoma Drynariae, processed Radix Aconiti Kusnezoffii, processed Semen Strychnos nux vomica, Cortex Phellodendri, Rhizoma Dioscoreae, Pheretima, and Herba Mori with 70% ethanol for 3 times, with the amount of alcohol added being 6 times / time and the extraction time being 1.5 hours / time, filter out the alcohol extract, recover the ethanol, and concentrate under reduced pressure to a relative density of 1.28-1.30 (50°C), and store the extract in a separate container; 3) Preparation of water extract: add 8 times water to Herba Epimedii, Radix Glycyrrhizae, Radix Achyranthis Bidentatae, Flos Lonicerae, Fructus Mume, Herba Ephedrae, Flos Carthami, and Herba Glechomae, extract 3 times, each time for 1.5 hours; The medicinal liquid is combined with the medicinal liquid of the volatile oil extracting medicinal material, and concentrated under reduced pressure to a relative density of 1.045-1.065 (50° C.), and impurities are removed by centrifugation. The supernatant is concentrated under reduced pressure to a relative density of 1.28-1.30 (50° C.), and the extract is used for standby use; 4) Preparation of Babu ointment: Combine the water extract and the alcohol extract, weigh the matrix material to make a matrix, add volatile oil, lauric nitrogen Ketone, propylene glycol, propylparaben, ethylparaben, disodium edetate, traditional Chinese medicine extract, stirring and mixing, coating, slicing and packaging.

2. The preparation method according to claim 1, characterized in that The matrix material comprises: sodium polyacrylate, carbomer, gelatin, sodium alginate, peach gum, glycerin, sodium hydroxide and purified water, and the weight ratio of sodium polyacrylate, carbomer, gelatin, sodium alginate, peach gum, glycerin, sodium hydroxide and purified water is 3.6:4:6:1-12:9:30:1.5:

40.

3. The preparation method according to claim 1, characterized in that: The weight ratio of the water extract to the alcohol extract and the matrix material is 1:10-30.

4. The preparation method according to claim 2, characterized in that: The weight ratio of the gelatin to sodium alginate is 1:0.1-1.

5. A method for preparing a traditional Chinese medicine muscle and bone plaster, comprising: 1) Preparation of volatile oil: soak the seven herbs of Notopterygium wilfordii, Asarum, Myrrha (processed), Cinnamon twig, Red ginseng, Acanthopanax senticosus, and Pilose antler for 2 hours, then extract the volatile oil by steam distillation, and store the volatile oil and the medicinal solution in a separate container; 2) Preparation of alcohol extract: extract the residue obtained from the preparation of volatile oil with 10 medicinal materials including Radix Dipsaci, Rhizoma Drynariae, processed Radix Aconiti Kusnezoffii, processed Semen Strychnos nux vomica, Cortex Phellodendri, Rhizoma Dioscoreae, Pheretima, and Herba Mori with 70% ethanol for 3 times, with the amount of alcohol added being 6 times / time and the extraction time being 1.5 hours / time; filter out the alcohol extract, recover the ethanol, and concentrate under reduced pressure to a relative density of 1.28-1.30 (50°C), and store the extract in a separate container; 3) Preparation of microemulsified samples: Mix the obtained volatile oil with the co-surfactant and stir evenly to form an oil phase; gradually add the surfactant to the oil phase at 35°C and stir evenly to form colostrum; gradually add all the obtained alcohol extracts under the action of a high shear emulsifier at 10,000 rpm; perform ultrasonic treatment at a frequency of 20 kHz for 20 minutes to form a stable microemulsion; 4) Preparation of water extract: add 8 times water to epimedium, liquorice, Achyranthes bidentata, honeysuckle, black plum, ephedra, safflower, and snakehead, extract 3 times, each extraction time is 1.5 hours. Combine the liquid with the liquid of volatile oil extract, decompress and concentrate to a relative density of 1.045-1.065 (50°C), centrifuge to remove impurities, decompress and concentrate the supernatant to a relative density of 1.28-1.30 (50°C), and prepare the extract for use; 5) Preparation of Babu ointment: combine the water extract and the microemulsion, weigh sodium polyacrylate, carbomer homopolymer, gelatin for capsule, sodium alginate, peach gum, glycerin, sodium hydroxide and purify to make a matrix, propylene glycol, propylparaben, ethylparaben, disodium edetate, and Chinese medicine extract, stir to mix, apply, slice, and package.

6. The preparation method according to claim 5, characterized in that: The co-surfactant is selected from propylene glycol or ethanol, and the volume weight ratio of the co-surfactant to the volatile oil is 1g:0.5-2ml.

7. The preparation method according to claim 5, characterized in that: The surfactant is one or more of Tween 80, lecithin, and Span 80, preferably Tween 80; the volume weight ratio of the surfactant to the volatile oil is 1g:2-6ml.

8. The preparation method according to any one of claims 1 to 7, characterized in that: The dosage of the medicinal materials is as follows: 7-23 parts by weight of processed Chuanwu, 7-23 parts by weight of processed Caowu, 7-23 parts by weight of processed Strychnos nux vomica, 7-23 parts by weight of Epimedium, 7-23 parts by weight of Achyranthes bidentata, 7-23 parts by weight of Notopterygium wilfordii, 7-23 parts by weight of Cynomorium cyrtonema, 7-23 parts by weight of Phellodendron chinense, 7-23 parts by weight of Agkistrodon amurense, 7-23 parts by weight of Agkistrodon davidianus, 4-16 parts by weight of Pilose antler, 7-23 parts by weight of Dipsacus asper, 7-23 parts by weight of Plum, 2-10 parts by weight of asarum, 7-23 parts by weight of ephedra, 7-23 parts by weight of cassia twig, 7-23 parts by weight of safflower, 7-23 parts by weight of Acanthopanax senticosus, 7-23 parts by weight of honeysuckle, 7-23 parts by weight of earthworm, 7-23 parts by weight of mistletoe, 7-23 parts by weight of liquorice, 7-23 parts by weight of scalded drynaria, 7-23 parts by weight of Radix Glehniae, 7-23 parts by weight of myrrh (processed), 7-23 parts by weight of red ginseng.

9. A Babu ointment obtained by the preparation method according to any one of claims 1 to 8.

10. Use of the Babu plaster as claimed in claim 9 in the preparation of analgesic drugs.

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