CN117338892B

CN117338892B - Gel emplastrum for treating arthralgia and preparation method thereof

Info

Publication number: CN117338892B
Application number: CN202311571585.8A
Authority: CN
Inventors: 任燕; 李仁彪; 肖贵梅
Original assignee: Guizhou University
Current assignee: Guizhou University
Priority date: 2023-11-23
Filing date: 2023-11-23
Publication date: 2024-11-01
Anticipated expiration: 2043-11-23
Also published as: CN117338892A

Abstract

The invention discloses a gel emplastrum for treating arthralgia, which is prepared from radix aconiti, asarum, rhizoma atractylodis, radix angelicae pubescentis, radix achyranthis bidentatae, whole angelica sinensis, rhizoma dioscoreae nipponicae, obscured homalomena rhizome, cortex schizophragmatis integrifolii radicis, radix clematidis, lignum pini nodi, red graminei, herba taxilli, rhizoma cibotii, cortex acanthopanacis, caulis spatholobi, rhizoma sparganii and rhizoma curcumae. The invention has better viscosity and formability, has the functions of dispelling wind and removing dampness, strengthening tendons and bones, removing blood stasis and relieving pain, and is suitable for people suffering from rheumatalgia.

Description

Gel emplastrum for treating arthralgia and preparation method thereof

Technical Field

The invention relates to a gel emplastrum for treating arthralgia and a preparation method thereof, belonging to the technical field of medicines.

Background

Arthralgia is a common disease and is mainly manifested by gout, and the arthralgia is caused by factors such as inappetence, daily decline of kidney qi, maladjustment of evacuation, overnutrition and the like. According to the analysis of traditional Chinese medicine, arthralgia is related to human tendons and qi and blood, and yang qi deficiency can not nourish tendons, so that fibromyalgia and the like are caused. Mention is made in "Su & Bi Lun": the three qi are mixed to form arthralgia, the qi is reversed to form arthralgia, the qi is recovered from the arthralgia and does not combine with wind-cold-dampness, so that the arthralgia is not formed, the occurrence of the arthralgia is related to the strength of healthy qi and defensive qi, if the yang qi of a human body is deficient, the function of resisting exogenous evil is weakened, and wind-cold-dampness evil is caused to enter by deficiency; in addition, if the healthy qi is deficient, the ability to expel pathogenic factors out is reduced, pathogenic wind-cold-dampness stays in the muscles and bones, and the meridians are obstructed and qi and blood are obstructed, resulting in arthralgia. Irregular diet, overfatigue and the like are all causes of morbidity. Because of individual differences, arthralgia is not the best treatment method, but can be treated by traditional Chinese medicine physiotherapy, external medicines and medicines.

The gel emplastrum is the earliest in Germany, is called a sizing cataplasm after being developed by Japanese scholars, has good moisture retention property of a water-soluble matrix, small skin irritation, high bioavailability and large drug loading, and is more suitable for the characteristics of more components and large dosage like traditional Chinese medicines. Gel patches have many advantages. First, because of transdermal preparation administration, the administration mode can avoid liver first pass effect and reduce irritation to gastrointestinal tract. Second, fluctuations in blood concentration caused by oral administration can be avoided. Third, the administration time can be prolonged and the number of administrations can be reduced. Fourth, the emplastrum can bear more dosage, is easy to attach to the skin, has small irritation and is convenient to use. However, the plaster has certain defects such as unstable product quality, large dosage, easy plaster removal, plaster leakage and the like.

The invention has the advantages that the extraction process is carried out by an orthogonal test method, the matrix prescription is convenient and reliable to find, the plaster under the optimal matrix prescription has better viscosity and formability, the high-efficiency liquid phase method is used for detecting the matrix content, the quality standard is stable, the preparation process of the compound arthralgia plaster is feasible, and the arthralgia prescription has good effects of dispelling wind and removing dampness, strengthening tendons and bones, removing blood stasis and relieving pain, thereby achieving the expected purpose of subject design.

Disclosure of Invention

The invention aims to provide a gel emplastrum for treating arthralgia and a preparation method thereof. The gel emplastrum has the effects of dispelling wind and removing dampness, strengthening tendons and bones, removing blood stasis and relieving pain, is used for treating rheumatalgia, and is suitable for people suffering from rheumatalgia. The preparation operation is easy, and the prepared plaster has better viscosity and formability and better product quality.

In order to solve the technical problems, the invention is realized by adopting the following technical scheme:

A gel emplastrum for treating arthralgia comprises the following medicinal active ingredients in parts by weight: is prepared from radix aconiti preparata 90-150 parts, asarum sieboldii 40-80 parts, rhizoma atractylodis 60-120 parts, radix angelicae pubescentis 60-120 parts, achyranthes bidentata 60-120 parts, angelica sinensis 90-150 parts, rhizoma dioscoreae nipponicae 200-400 parts, rhizoma homalomenae 200-400 parts, cortex schizophragmatis integrifolii radicis 200-400 parts, radix clematidis 130-230 parts, pine node 100-200 parts, red graminea 100-200 parts, herba taxilli 90-150 parts, rhizoma cibotii 90-150 parts, cortex acanthopanacis 90-150 parts, caulis spatholobi 100-200 parts, rhizoma sparganii 90-150 parts and rhizoma curcumae 90-150 parts.

The gel emplastrum for treating arthralgia comprises the following medicinal active ingredients in parts by weight: is prepared from 100-140 parts of prepared common monkshood mother root, 50-70 parts of asarum, 70-110 parts of rhizoma atractylodis, 70-110 parts of radix angelicae pubescentis, 70-110 parts of achyranthes bidentata, 100-140 parts of whole angelica sinensis, 250-350 parts of Ningpo Yam rhizome, 250-350 parts of obscured homalomena rhizome, 250-350 parts of cortex schizophragmatis integrifolii radicis, 150-210 parts of radix clematidis, 120-180 parts of pine node, 80-120 parts of red graminea, 100-140 parts of mistletoe, 100-140 parts of rhizoma cibotii, 100-140 parts of cortex acanthopanacis, 120-180 parts of suberect spatholobus stem, 100-140 parts of rhizoma sparganii and 100-140 parts of rhizoma curcumae.

Specifically, the gel emplastrum for treating arthralgia comprises the following medicinal active ingredients in parts by weight: is prepared from prepared Sichuan aconite root 120 parts, asarum herb 60 parts, atractylodes rhizome 90 parts, pubescent angelica root 90 parts, achyranthes root 90 parts, chinese angelica root 120 parts, ningpo Yam rhizome 300 parts, homalomena rhizome 300 parts, dried rhizome of rehmannia 300 parts, clematis chinensis 180 parts, pine node 150 parts, red rice 100 parts, loranthus mulberry mistletoe 120 parts, cibotium barometz 120 parts, cortex acanthopanacis 120 parts, spatholobus stem 150 parts, burreed tuber 120 parts, zedoary 120 parts.

The preparation method of the gel emplastrum for treating arthralgia comprises the following steps:

(1) Weighing the medicinal materials according to the prescription proportion, crushing into coarse materials, accurately weighing 15-20g of the total mass of the medicinal materials by an electronic analytical balance, soaking for 18-30h by 12-18 times of ethanol, extracting for 2-4h by reflux, filtering, and drying the filtrate at 60-80 ℃ to obtain a traditional Chinese medicine ointment for later use;

(2) Accurately weighing 0.55-0.75g of sodium polyacrylate, 0.45-0.65g of kaolin and 6.5-7.5g of glycerin, and uniformly mixing to obtain a phase A for later use;

(3) Accurately weighing 0.03-0.05g of aluminum glycinate, 10-14g of tartaric acid and 0.2-0.4g of menthol, and uniformly mixing to obtain a phase B for later use;

(4) Heating the phase A on a water bath kettle at 60-80 ℃ for 6-8min, adding the phase B into the phase A, and continuously and rapidly stirring for 6-8min to obtain a gel matrix for later use;

(5) Adding the Chinese medicinal ointment into gel matrix, stirring for 20-30min, spreading the obtained ointment on 8cm x 12cm non-woven fabric, and cooling and solidifying in shade to obtain gel patch.

In the step (1), the medicinal materials are weighed according to the prescription proportion, crushed into coarse materials, the total mass of the medicinal materials is accurately weighed to be 17.1g by an electronic analytical balance, the medicinal materials are soaked for 24 hours by 15 times of ethanol, the reflux extraction is carried out for 3 hours, the filtration is carried out, and the filtrate is dried at 70 ℃ to obtain the traditional Chinese medicine ointment for standby.

In the foregoing step (2), 0.63g of sodium polyacrylate, 0.55g of kaolin and 7g of glycerin were precisely weighed as phase A for use.

In the step (3), 0.04g of aluminum glycinate, 12g of tartaric acid and 0.3g of menthol are precisely weighed as phase B for standby.

In the step (4), the phase A is heated on a water bath kettle with the temperature of 70 ℃ and is rapidly stirred for 7min, the phase B is added into the phase A, and the rapid stirring is continued for 7min to obtain a gel matrix for later use;

In the step (5), the traditional Chinese medicine ointment is added into the gel matrix, stirred for 25min, the obtained ointment is paved on non-woven fabrics with the length of 8cm and the length of 12cm, and the non-woven fabrics are placed in a shade place for cooling and solidifying to obtain the gel emplastrum.

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

The gel emplastrum for treating arthralgia is prepared from prepared radix aconiti, asarum, rhizoma atractylodis, radix angelicae pubescentis, achyranthes bidentata, whole angelica sinensis, ningpo Yam rhizome, obscured homalomena rhizome, cortex schizophragmatis integrifolii radicis, radix clematidis, pine knots, red cereal, mistletoe, rhizoma cibotii, cortex acanthopanacis, caulis spatholobi, rhizoma sparganii and rhizoma curcumae. Wherein radix Aconiti is dried mother root of Aconitum carmichaeli Aconitumcarmichaelii Debx of Ranunculaceae; digging in the last ten days of 6 months to 8 months, removing the son roots, the fibrous roots and the sediment, and sun drying; pungent and bitter in taste and warm in nature; has great toxicity; return to heart, liver, kidney and spleen meridians; has effects of dispelling pathogenic wind, removing dampness, warming channels and relieving pain; can be used for treating arthralgia due to wind-cold-dampness, arthralgia, psychroalgia of heart and abdomen, cold hernia pain, and anesthesia and pain; The prepared radix Aconiti is processed product of radix Aconiti. Herba asari is dried root and root of herba asari Asarumheterotropoides fr, schmidt var man dshuricum (maxim.) Kitag of Ma Jiaoling family; digging in summer in fruit ripening period or early autumn, removing overground part and silt, and drying in shade; pungent taste and warm nature; return to heart, lung and kidney meridians; has effects of relieving exterior syndrome, dispelling cold, dispelling pathogenic wind, relieving pain, inducing resuscitation, warming lung, and resolving fluid retention; can be used for treating common cold due to wind-cold, headache, toothache, nasal obstruction, nasal discharge, allergic rhinitis, nasosinusitis, rheumatalgia, phlegm retention, asthma and cough. Rhizoma Atractylodis is dried rhizome of Atractylodes lancea Atractylodes lancea (thunder.) DC or Atractylodes lancea Atractylodes chinensis (DC.) Koidz; Digging in autumn and pounding, removing sediment, sun drying, and removing fibrous roots; pungent and bitter in taste and warm in nature; spleen, stomach and liver meridian; has effects of eliminating dampness, invigorating spleen, dispelling pathogenic wind, dispelling cold, and improving eyesight; can be used for treating damp obstruction of middle energizer, abdominal distention, diarrhea, edema, tinea pedis, rheumatalgia, common cold due to wind-cold, night blindness, and dim eyesight. Radix Angelicae Pubescentis is dry root of Angelica gigas nakai Angelica pubescens Maxim. F. Biseria Shaman et Yuan of Umbelliferae; digging when the spring is at the beginning Miao Gang for germination or the stem leaves are withered at the end of autumn, removing fibrous roots and sediment, drying to be semi-dry, piling for 2-3 days, softening and drying to be full dry; Pungent and bitter in taste and slightly warm in nature; kidney and bladder meridian; has effects of dispelling pathogenic wind, removing dampness, relieving arthralgia, and relieving pain; can be used for treating arthralgia due to wind-cold-dampness, lumbago, gonalgia, headache due to wind-damp evil, and headache due to wind-cold-dampness. The radix Achyranthis bidentatae is dry root of achyranthes bidentata ACHYRANTHES BIDENTATA Bl. belonging to Amaranthaceae; bitter, sweet and sour in taste and neutral in nature; enter liver and kidney meridians; has effects of removing blood stasis, dredging channels, nourishing liver and kidney, strengthening tendons and bones, inducing diuresis, treating stranguria, and promoting blood circulation; can be used for treating amenorrhea, dysmenorrhea, soreness of waist and knees, weakness of tendons and bones, stranguria, edema, headache, dizziness, toothache, aphtha, hematemesis, and epistaxis. Radix Angelicae sinensis is dry root of Angelica sinensis ANGELICA SINENSIS (Oliv.) Diels of Umbelliferae; Digging in the late autumn, removing fibrous roots and silt, bundling into small bundles after water is slightly evaporated, and slowly smoking with smoke; the whole Chinese angelica comprises the head, middle and tail of Chinese angelica; sweet and pungent taste and warm nature; enter liver, heart and spleen meridians; has effects of replenishing blood, promoting blood circulation, regulating menstruation, relieving pain, loosening bowel, and relieving constipation; can be used for treating sallow complexion due to blood deficiency, dizziness, palpitation, menoxenia, amenorrhea, dysmenorrhea, abdominal pain due to deficiency-cold, rheumatalgia, traumatic injury, carbuncle, skin ulcer, and constipation due to intestinal dryness; the wine angelica has the effects of promoting blood circulation and dredging channels; can be used for treating amenorrhea, dysmenorrhea, rheumatalgia, traumatic injury. The Dioscorea nipponica Makino is dried rhizome of Dioscorea nipponica Makino Dioscorea nipponica Makino of Dioscoreaceae; Digging in spring and autumn, cleaning, removing fibrous root and skin, and sun drying; sweet and bitter in taste and warm in nature; enter liver, kidney and lung meridians; has effects of dispelling pathogenic wind, removing dampness, relaxing muscles and tendons, dredging collaterals, promoting blood circulation, relieving pain, eliminating phlegm, and relieving cough; can be used for treating rheumatalgia, joint swelling, pain and numbness, traumatic injury, lumbar sprain, cough and asthma. The rhizoma homalomenae is dried rhizome of rhizoma homalomenae Homalomena occulta (Lour.) Schott of Araceae; bitter and pungent in flavor and warm in nature. Enter liver and kidney meridians; has effects of dispelling pathogenic wind and dampness, and strengthening tendons and bones; can be used for treating arthralgia due to wind-cold-dampness, lumbago, gonalgia, contracture, numbness, and flaccidity of tendons and bones. Cortex Illici radicis is dried bark of cortex Illici radicis Illicium difengpi K.I.B.et K.I.M. of Magnoliaceae; Slightly pungent and astringent in flavor and warm in nature; the Chinese medicinal composition has small toxicity; enter the bladder and kidney meridians; has effects of dispelling pathogenic wind, removing dampness, activating qi-flowing and relieving pain; can be used for treating rheumatalgia, lumbago due to fatigue. Radix Clematidis is dried root and rhizome of Clematis chinensis CLEMATISCHINENSIS OSBECK, clematis chinensis Clematis hexapetala pall, clematis chinensis Clematis manshurica rupr; pungent and salty taste, warm nature; enter the bladder meridian; has effects of dispelling pathogenic wind and dampness, and dredging channels and collaterals; can be used for treating rheumatalgia, numbness of limbs, spasm of tendons and vessels, and difficulty in flexing and extending. The Pinus koraiensis is the branch nodule of Pinaceae plant Pinus yunnanensis (Pinus yunnanensis Franch); bitter taste and warm nature; has effects of dispelling pathogenic wind, removing dampness, relieving rigidity of muscles, activating collaterals, promoting blood circulation and stopping bleeding; can be used for treating arthralgia, muscle and bone pain, paralysis and weakness of foot, and traumatic pain. The red grass is root of bulbil Ai Ma (Laportea bulbifera (sieb. Etzace) wedd) of nettle family, pungent taste and warm nature; has effects of dispelling pathogenic wind, removing dampness, promoting blood circulation, and removing blood stasis; it is used for treating rheumatalgia, numbness of limbs, traumatic injury, fracture pain, and menoxenia. The herba Taxilli is dry leaf-bearing stem and branch of herba Taxilli Taxillus chinensis (DC.) Danser of Moraceae; Harvesting in winter to next spring, removing coarse stems, cutting, drying, or steaming and drying; bitter and sweet in taste and neutral in nature; enter liver and kidney meridians; has effects of dispelling pathogenic wind and dampness, nourishing liver and kidney, strengthening tendons and bones, and relieving fetal vigor; can be used for treating rheumatalgia, soreness of waist and knees, weakness of tendons and bones, metrorrhagia, metrostaxis, blood leakage during pregnancy, fetal irritability, and dizziness. Rhizoma Cibotii is dried rhizome of rhizoma Cibotii Cibotiumbarometz (l.) j.sm; bitter and sweet in taste and warm in nature; enter liver and kidney meridians; has effects in dispelling pathogenic wind and dampness, nourishing liver and kidney, and strengthening waist and knee; can be used for treating rheumatalgia, soreness of waist and knees, and weakness of lower limbs. Cortex Acanthopancis is the dried root bark of Acanthopanax gracilistylus Acanthopanax gracilistylus W.W.Smith; Pungent and bitter in taste and warm in nature; enter liver and kidney meridians; has effects of dispelling pathogenic wind, removing dampness, tonifying liver and kidney, strengthening tendons and bones, inducing diuresis and relieving swelling; can be used for treating rheumatalgia, flaccidity of tendons and bones, infantile late movement, asthenia, edema, and tinea pedis. Caulis Spatholobi is dried rattan of Spatholobus stem Spatholobus suberectus Dunn of Leguminosae; bitter and sweet in taste and warm in nature; enter liver and kidney meridians; has effects of promoting blood circulation, replenishing blood, regulating menstruation, relieving pain, relaxing tendons, and activating collaterals; it can be used for treating menoxenia, dysmenorrhea, amenorrhea, rheumatalgia, numbness, paralysis, and sallow complexion due to blood deficiency. The rhizoma Sparganii is dry tuber of Sparganii Sparganiumstoloniferum Buch-ham; Pungent and bitter in taste and mild in nature; enter liver and spleen meridians; has effects of removing blood stasis, activating qi-flowing, resolving food stagnation and relieving pain; can be used for treating abdominal mass, dysmenorrhea, amenorrhea due to blood stasis, chest pain, and food stagnation and distending pain. Zedoary is the dried rhizome of Curcuma zedoary Curcuma phaeocaulis VaL, curcuma zedoary Curcumakuuangsiensis S.G.Leeetc.F.Liang or Curcuma wenyujin Y.ChenetC.Ling; pungent and bitter in taste and warm in nature; enter liver and spleen meridians; has effects of promoting qi circulation, removing blood stasis, and relieving pain; is used for treating abdominal mass, amenorrhea due to blood stasis, chest pain, and distending pain due to food stagnation.

And (3) square solution:

The main pathogenesis of arthralgia syndrome is that qi and blood are not smooth due to blockage of channels by pathogenic wind-cold-dampness, and the formula is characterized in that the Chinese medicinal herbs with the functions of dispelling wind and removing dampness, strengthening tendons and bones and activating blood and relieving pain are monarch drugs; radix Clematidis, caulis Spatholobi and radix et rhizoma Rhei can dispel wind and remove dampness and dredge channels; for long-term consumption of qi and blood to affect liver and kidney, it can dispel wind-damp, tonify liver and kidney, strengthen tendons and bones with Loranthus mulberry mistletoe, cibotii, acanthopanax bark, etc.; the radix aconiti can dispel wind and remove dampness, dispel cold and relieve pain, and is used as a ministerial drug for assisting a monarch drug in dispelling wind and removing dampness, strengthening tendons and bones and activating blood and relieving pain; herba asari can search tendons and bones for pathogenic wind-cold-dampness, unblock collaterals and relieve pain; pine knots and rhizoma atractylodis are used for strengthening spleen and eliminating dampness; du Huo can dispel wind, dispel cold, dispel dampness and alleviate pain; because the wind-damp arthralgia is caused by long-term disease into collaterals, and blood stasis and turbid phlegm block the meridians, and the non-blood-breaking products cannot be transformed, the Chinese angelica, the rhizoma sparganii, the rhizoma zedoariae and the like are used for breaking blood and dissolving stasis, promoting qi circulation and relieving pain, and the effects of treating wind and treating the blood first and the blood moving wind and self-extinguishing are adopted as adjuvant drugs; achyranthes root, radix Achyranthis bidentatae, having the effects of nourishing liver and kidney, strengthening tendons and bones, and guiding drugs the medicine goes downwards to dredge the channels and collaterals, is an adjuvant drug. The medicines are combined together to play the roles of dispelling wind, removing dampness, strengthening tendons and bones, removing blood stasis and relieving pain.

Compared with the prior art, the beneficial effects are as follows:

1. the method for extracting and searching the matrix by the orthogonal test method is convenient and reliable, the plaster with the optimal matrix prescription has better viscosity and formability, the highest oleanolic acid content detected by the high-efficiency liquid phase method can reach 0.05 percent, the quality standard is stable, the preparation process of the compound arthralgia plaster is feasible, and the expected purpose of the subject design is achieved.

The low and high dose groups of the arthralgia prescription and the prednisone acetate group have obvious inhibition effects on the ear swelling of the mice caused by the dimethylbenzene, can reduce the ear swelling of the mice, and indicate that the arthralgia prescription has good anti-inflammatory effect. Each dosing group had statistical significance (p < 0.05) by comparison to the blank. The swelling degree of the high-dose group of the arthralgia prescription is obviously smaller than that of the low-dose group, which indicates that the anti-inflammatory effect of the high-dose group is better than that of the low-dose group. Therefore, the invention has good effects of easing pain and inhibiting inflammation, and can obviously reduce the frequency of torsion of mice caused by the stimulation of acetic acid to abdominal cavities and inhibit ear swelling of mice caused by dimethylbenzene.

The gel plaster prepared by the prescription selected by the experiment has good coating property, smooth and uniform texture, soft and smooth plaster surface, no obvious large particles, fewer bubbles, good adhesion and no residue. The arthralgia gel emplastrum is characterized by adhering to the characteristic advantages of traditional Chinese medicines, is prepared by innovatively modifying traditional Chinese medicine emplastrum by applying modern preparation equipment and a modern transdermal administration technology of a traditional Chinese medicine cataplasm, and has practical and profound significance for the innovative development of the traditional Chinese medicine emplastrum.

Drawings

Fig. 1: example 1 drug infusion process diagram;

fig. 2: example 1 Chinese medicinal ointment;

fig. 3: example 1 gel patch

Fig. 4: detecting the oleanolic acid content and controlling the spectrogram;

fig. 5: detecting the oleanolic acid content of a sample No. 1 spectrogram;

fig. 6: detecting the oleanolic acid content of a sample No.2 spectrogram;

Fig. 7: measuring an oleanolic acid content standard curve by a high performance liquid chromatography method;

fig. 8: a mouse torsion experiment process diagram;

fig. 9: a dimethylbenzene induced ear swelling experimental process diagram.

Detailed Description

The invention is further illustrated by the following examples, which are not intended to be limiting.

Example 1.

Prescription: prepared Sichuan aconite root 12g, asarum herb 6g, atractylodes rhizome 9g, pubescent angelica root 9g, achyranthes root 9g, chinese angelica root 12g, ningpo Yam rhizome 30g, homalomena rhizome 30g, dried rhizome of rehmannia 30g, clematis chinensis 18g, pine node 15g, red rice 10g, loranthus mulberry mistletoe 12g, cibotium barometz 12g, cortex acanthopanacis 12g, spatholobus stem 15g, burreed tuber 12g and zedoary 12g.

The process comprises the following steps: (1) Weighing the medicinal materials according to the prescription proportion, crushing into coarse materials, accurately weighing 17.1g of the total mass of the medicinal materials by an electronic analytical balance, soaking for 24 hours by 15 times of ethanol, extracting for 3 hours under reflux, filtering, and drying the filtrate at 70 ℃ to obtain traditional Chinese medicine ointment for later use;

(2) Accurately weighing 0.63g of sodium polyacrylate, 0.55g of kaolin and 7g of glycerol as phase A for later use;

(3) Accurately weighing 0.04g of aluminum glycinate, 12g of tartaric acid and 0.3g of menthol as a phase B for later use;

(4) Heating the phase A on a water bath kettle at 70 ℃ and rapidly stirring for 7min, adding the phase B into the phase A, and continuously and rapidly stirring for 7min to obtain a gel matrix for later use;

(5) Adding the Chinese medicinal ointment into gel matrix, stirring for 25min, spreading the obtained ointment on 8cm x 12cm non-woven fabric, and cooling and solidifying in shade to obtain gel patch.

The usage amount is as follows: every 12 hours, a gel emplastrum is used, and 10 days is a treatment course.

Example 2.

Prescription: 9g of prepared common monkshood mother root, 4g of asarum, 6g of swordlike atractylodes rhizome, 6g of pubescent angelica root, 6g of twotooth achyranthes root, 9g of whole Chinese angelica, 20g of Ningpo Yam rhizome, 20g of obscured homalomena rhizome, 20g of ground cover, 13g of Chinese clematis, 10g of pine node, 10g of red grass, 9 of Chinese taxillus twig, 9 of east Asian tree fern rhizome, 9 of cortex acanthopanacis, 10 of suberect spatholobus stem, 9 of common burreed rhizome and 9 of zedoary.

The process comprises the following steps: (1) Weighing the medicinal materials according to the prescription proportion, crushing into coarse materials, accurately weighing the total mass of the medicinal materials to be 15g by using an electronic analytical balance, soaking the medicinal materials for 18h by using 12 times of ethanol, extracting the medicinal materials under reflux for 2h, filtering, and drying the filtrate at 60 ℃ to obtain a traditional Chinese medicine ointment for later use;

(2) Accurately weighing 0.55g of sodium polyacrylate, 0.45g of kaolin and 6.5g of glycerol, and uniformly mixing to obtain a phase A for later use;

(3) Accurately weighing 0.03g of aluminum glycinate, 10g of tartaric acid and 0.2g of menthol, and uniformly mixing to obtain a phase B for later use;

(4) Heating the phase A on a water bath kettle at 60 ℃ and rapidly stirring for 6min, adding the phase B into the phase A, and continuously and rapidly stirring for 6min to obtain a gel matrix for later use;

(5) And adding the traditional Chinese medicine ointment into a gel matrix, stirring for 20min, spreading the obtained ointment on non-woven fabrics with the thickness of 8cm x 12cm, and placing the non-woven fabrics in a shade place for cooling and solidifying to obtain the gel emplastrum.

Example 3.

Prescription: 15g of prepared common monkshood mother root, 8g of manchurian wildginger, 12g of swordlike atractylodes rhizome, 12g of pubescent angelica root, 12g of twotooth achyranthes root, 15g of whole Chinese angelica, 40g of Ningpo Yam rhizome, 40g of obscured homalomena rhizome, 40g of ground cover, 23g of Chinese clematis, 20g of pine node, 20g of red grass, 15g of Chinese taxillus twig, 15g of east Asian tree fern rhizome, 15g of cortex acanthopanacis, 20g of suberect spatholobus stem, 15g of common burreed rhizome and 15g of zedoary.

The process comprises the following steps: (1) Weighing the medicinal materials according to the prescription proportion, crushing into coarse materials, accurately weighing the total mass of the medicinal materials to be 20g by using an electronic analytical balance, soaking the medicinal materials for 30h by 18 times of ethanol, extracting the medicinal materials under reflux for 4h, filtering, and drying the filtrate at 80 ℃ to obtain a traditional Chinese medicine ointment for later use;

(2) Accurately weighing 0.75g of sodium polyacrylate, 0.65g of kaolin and 7.5g of glycerol, and uniformly mixing to obtain a phase A for later use;

(3) Accurately weighing 0.05g of aluminum glycinate, 14g of tartaric acid and 0.4g of menthol, and uniformly mixing to obtain a phase B for later use;

(4) Heating the phase A on a water bath kettle at 80 ℃ and rapidly stirring for 8min, adding the phase B into the phase A, and continuously and rapidly stirring for 8min to obtain a gel matrix for later use;

(5) Adding the Chinese medicinal ointment into gel matrix, stirring for 30min, spreading the obtained ointment on 8cm x 12cm non-woven fabric, and cooling and solidifying in shade to obtain gel patch.

Example 4.

Prescription: 11g of prepared common monkshood mother root, 8g of manchurian wildginger, 8g of swordlike atractylodes rhizome, 10g of pubescent angelica root, 12g of twotooth achyranthes root, 9g of Chinese angelica, 25g of Ningpo Yam rhizome, 30g of obscured homalomena rhizome, 40g of ground cover, 22g of Chinese clematis, 10g of pine node, 12g of red grass, 15g of Chinese taxillus twig, 14g of east Asian tree fern rhizome, 12g of cortex acanthopanacis, 20g of suberect spatholobus stem, 10g of common burreed rhizome and 15g of zedoary.

The process comprises the following steps: (1) Weighing the medicinal materials according to the prescription proportion, crushing into coarse materials, accurately weighing 18g of the total mass of the medicinal materials by an electronic analytical balance, soaking for 28h by using 14 times of ethanol, extracting for 2h under reflux, filtering, and drying the filtrate at 65 ℃ to obtain traditional Chinese medicine ointment for later use;

(2) Accurately weighing 0.65g of sodium polyacrylate, 0.50g of kaolin and 7.5g of glycerol, and uniformly mixing to obtain a phase A for later use;

(3) Accurately weighing 0.035g of aluminum glycinate, 11g of tartaric acid and 0.35g of menthol, and uniformly mixing to obtain a phase B for later use;

(4) Heating the phase A on a water bath kettle at 65 ℃ and rapidly stirring for 8min, adding the phase B into the phase A, and continuously and rapidly stirring for 8min to obtain a gel matrix for later use;

Example 5.

Prescription: 9g of prepared common monkshood mother root, 4g of asarum, 10g of swordlike atractylodes rhizome, 12g of pubescent angelica root, 7g of twotooth achyranthes root, 12g of whole Chinese angelica, 40g of Ningpo Yam rhizome, 30g of obscured homalomena rhizome, 35g of ground cover, 15g of Chinese clematis, 10g of pine node, 10g of red grass, 15g of Chinese taxillus twig, 11g of east Asian tree fern rhizome, 9g of cortex acanthopanacis, 18g of suberect spatholobus stem, 13g of common burreed rhizome and 13g of zedoary.

The process comprises the following steps: (1) Weighing the medicinal materials according to the prescription proportion, crushing into coarse materials, accurately weighing the total mass of the medicinal materials to be 16g by using an electronic analytical balance, soaking the medicinal materials in 14 times of ethanol for 20 hours, extracting the medicinal materials under reflux for 4 hours, filtering, and drying the filtrate at 70 ℃ to obtain a traditional Chinese medicine ointment for later use;

(2) Accurately weighing 0.70g of sodium polyacrylate, 0.60g of kaolin and 6.5g of glycerol, and uniformly mixing to obtain a phase A for later use;

(3) Accurately weighing 0.04g of aluminum glycinate, 11g of tartaric acid and 0.35g of menthol, and uniformly mixing to obtain a phase B for later use;

(4) Heating the phase A on a water bath kettle at 70 ℃ and rapidly stirring for 6min, adding the phase B into the phase A, and continuously and rapidly stirring for 6min to obtain a gel matrix for later use;

The invention carries out a great deal of experimental study, and the following results are obtained by the experimental study:

1 Process study

1.1 Optimization of extraction Process

1.1.1 Optimization procedure of extraction Process

The medicines are weighed according to the prescription proportion (the prescription of the example 1), crushed into coarse grains, accurately weighed by an electronic analytical balance (the total mass of the medicines is 17.1 g), placed in a 1000mL beaker, soaked by ethanol, and placed in a 2000mL round bottom flask after being soaked. Then the mixture is put into a matched electronic temperature-regulating electric heating sleeve, a spherical reflux condenser pipe is assembled at the mouth of the flask, the electric heating sleeve is electrified for heating, the state of boiling the solvent is kept, the mixture is taken out after a certain period of time, the mixture is filtered by a circulating water type multipurpose vacuum pump, a filter paper and a Buchner funnel while the mixture is hot, the obtained filtrate is put into a 500mL round bottom flask, the filtrate cannot exceed one third of the round bottom flask, the round bottom flask is put into a rotary evaporator for rotary evaporation, ethanol and most of water are removed, the final liquid is obtained, the liquid is put into a beaker, the beaker is put into an electric heating blast drying box, the temperature of the liquid is kept at 70 ℃, the medicine is dried, the ointment is obtained, the ointment is weighed, and the ointment rate is calculated. In the experimental design process, a quadrature test method is used for recording and guiding, 9 groups of experiments are prepared, and 3 horizontal quadrature tests are carried out by 4 factors of ethanol concentration, solvent consumption, reflux time and soaking time. The design extraction factors are as in table 1:

TABLE 1 orthogonality factors and levels

Using orthogonal test L ₉(3⁴) for extraction, designed as in table 2:

TABLE 2 orthogonal test of Chinese herbal medicine extraction

1.1.2 Extraction Process results

After 9 experiments, the results are shown in table 3:

TABLE 3 results of orthogonal experiments

According to the magnitude of the range R, visual analysis shows that the primary and secondary orders of the influence of the 4 factors on the extraction effect are as follows: the concentration of ethanol (A) > the dosage of solvent (B) > the reflux time (C) > the soaking time (D), and the optimal extraction process combination is initially determined to be A ₁B₃C₃D₂, namely the concentration of ethanol in reflux extraction is 60%, the dosage of solvent is 15 times of that of the medicinal materials, the medicinal materials are refluxed for 3 hours, and the medicinal materials are soaked for 24 hours.

1.1.3 Discussion

In the experimental condition, the experimental design relates to 3 levels of 4 factors, and in the experimental result, we can see that the concentration of the ethanol is the smallest in the three-level experiment, and according to the extremely poor size, the ethanol concentration is the largest factor affecting the extraction rate of medicinal materials, the extraction rates of different Chinese medicinal materials in different ethanol concentrations are different, but more Chinese medicinal materials are biased to low-concentration ethanol solution, and according to the analysis of the experimental result, the lower the ethanol concentration is, the higher the extraction rate is, and the more effective components in the medicinal materials are dissolved in water; from the extremely poor R, the solvent dosage is the second factor influencing the extraction rate of the medicine, and the analysis is carried out according to the use experiment result K of the solvent, and the extraction rate of the medicine is increased along with the increase of the solvent dosage, so that the larger the solvent dosage is, the better the solvent dosage is; from the above table, it is known that the length of the reflux time is the third factor affecting the extraction rate of the drug, and in the expression of the K value, the extraction rate becomes higher as the reflux time is longer; among the four factors, the R of the soaking time is smaller, but the soaking time has important influence on the extraction rate of the medicine, and experimental results show that the soaking time of the medicine is the best in 24 hours, but from the result of the K value, the difference between K1 and K2 and between K3 is obvious, and the numerical value of the K2 and the numerical value of the K3 are different and not great, so that the soaking time is more than 24 hours. Research shows that the temperature, extraction time, crushing degree and solvent have influence on the extraction rate, the permeation, dissolution and diffusion capacities of the active ingredients of the medicinal materials are increased along with the increase of the temperature, and the viscosity of the solution is reduced along with the increase of the temperature, so that the heating in the extraction can strengthen the movement of molecules, soften tissues and improve the solubility, thereby improving the extraction rate; the extraction rate of the Chinese herbal medicine components increases with the extension of the extraction time until equilibrium is reached; the finer the medicinal material is crushed, the larger the surface area is, the more the surface area is contacted with the solvent, and the higher the probability of substance coming out is, so the higher the extraction rate is; in addition, stirring, the amount of the extraction solvent, and the like have a certain relationship with the extraction yield.

1.2 Preparation Process optimization

1.2.1 Preparation of Compound arthralgia gel plaster

The gel plaster consists of three parts, namely a backing layer, an anti-sticking layer and paste. The back lining layer is made of non-woven fabrics, the price is low, and the purchase is easy; the anti-sticking layer is a protective layer of paste, and glass paper is better; the ointment is the part where the active ingredients of the medicinal materials exist, and is the key for determining the quality of the whole ointment. The ointment consists of active ingredients of medicinal materials and an ointment matrix, wherein the matrix consists of an adhesive, a regulator, a filler, a humectant and a transdermal enhancer. The matrix is selected from aluminum glycinate, sodium polyacrylate, glycerol, tartaric acid, kaolin and menthol. Except menthol, the other 5 materials have great influence on the molding quality of the plaster, so 11g of glycerin, 0.63g of sodium polyacrylate, 0.04g of aluminum glycinate, 0.12g of tartaric acid and 0.65g of kaolin are selected as setting standard lines, values are taken on the upper and lower parts of the usage amount of the materials, and a plurality of horizontal experiments are designed, wherein 0.30g of menthol is taken. The common orthogonal test table is used for designing a 5-factor 4 horizontal orthogonal test to find the optimal matching of matrix proportions.

Factor level design is as in table 4:

TABLE 4 orthogonal test factors and levels of plaster matrices

Common orthogonal table L ₁₆(4⁵) design experiments are shown in table 5:

TABLE 5 orthometric test of plaster matrix

Accurately weighing sodium polyacrylate, kaolin and glycerin according to an experimental design, and placing the sodium polyacrylate, the kaolin and the glycerin in a 100mL beaker to serve as a phase A; accurately weighing aluminum glycinate, tartaric acid and menthol, and placing on weighing paper as phase B. Heating the phase A on a water bath kettle at 70 ℃ for 7min of rapid stirring, adding the phase B into the phase A, continuously and rapidly stirring for 7min, spreading the obtained paste on non-woven fabrics with the thickness of 8cm x 12cm, placing the non-woven fabrics in a shade place, cooling and solidifying the non-woven fabrics, and repeating the steps to finish 16 experiments.

After the 16 experiments are completed, the plaster is sequentially paved at a shady place and stood for 48 hours, and the 16 formed plasters are scored according to subjective evaluation, mainly according to the appearance characters, film residues, skin following property and penetration degree of the plaster. Evaluation details are shown in Table 6:

TABLE 6 evaluation criteria for plaster matrix

And after the optimal matrix dosage proportion is obtained from the experimental result, adding the ointment extracted by the optimal extraction process, and testing the influence of different stirring time on the plaster by taking the stirring time as a factor, wherein the stirring time is designed to be 15min, 20min and 25min, and the stirring time corresponds to experiment groups 1, 2 and 3 respectively. Heating and stirring on a water bath kettle at 70 ℃ to obtain paste, spreading on 8cm x 12cm non-woven fabric while the paste is hot, and cooling to obtain the finished product. The patches of 3 groups of experiments were evaluated for heat resistance, initial adhesion and holding power.

1.2.2 Evaluation index of Compound arthralgia gel plaster

(1) Appearance characteristics: and placing the obtained molded emplastrum on a test bed, sequentially arranging, subjectively evaluating the appearance shape of the molded emplastrum, and executing the evaluation standard according to the standard.

(2) Heat resistance: taking 3 gel plasters to be tested, sequentially placing the 3 gel plasters in a 60 ℃ oven for heating for 2 hours, observing the penetration degree of the back of the gel plasters after the gel plasters are cooled, carrying out subjective evaluation on the gel plasters according to the relevant evaluation rules of the complaints, and observing the glossiness of the plaster surfaces, wherein the gel plasters still have viscosity after being lightly touched by fingers.

(3) Measurement of Primary adhesion: the initial adhesion is measured by adopting a slope rolling coin stopping method, a gel paste sample backing is fixed on a floor by using a double-sided adhesive tape, a slope slide rail is attached to the edge of the paste backing, the viscosity of the gel paste is upward, the slope is 13 degrees away from the ground, the length of the slide rail is 40cm, and coins are static at the position of the slide rail which is vertical to the ground by 9cm and roll. The rolling coin consists of 3 1-element coins adhered by glue, and the mass is 18g. After the coins roll down, the sliding distance of the coins on the surface of the plaster is measured by a ruler, and the quality of the initial adhesive force of the plaster is judged.

(4) Measurement of holding power: the test sample adhesive surface is flatly paved on a test bed, a hard plate is cushioned, a backing layer of the test sample adhesive surface is adhered on the hard plate by using adhesive tape, and a coiled preservative film with the quality of 95g and the width of 4cm is used as a test tool. Placing the adhesive plaster on the adhesive surface of the adhesive plaster, standing for 1min, turning the adhesive plaster for 180 degrees to enable the adhesive plaster to be placed below, hanging the adhesive plaster on the adhesive plaster, and recording the falling time of the adhesive plaster to judge the adhesive holding force of the adhesive plaster.

1.2.3 Results

Subjective scoring results for matrix prescription 16 experiments are shown in table 7:

TABLE 7 evaluation results of plaster matrix

The 16 groups of orthogonal tests are completed, and the subjective scores show that the 3 rd, 4 th, 11 th, 14 th and 15 th groups of tests have the best appearance shape, the 9 th group of the tests have the best membrane residue, the skin following property of the tests is good, the viscosity is good, the seepage degree of the 3 rd and 4 th groups of tests is the lowest, and the test effect is the best. The sensory score values were substituted into the corresponding experimental orthogonal tables to obtain the following, and the K and R values thereof were calculated as shown in table 8.

TABLE 8 results of orthogonal test of plaster matrix

From a comparison in the range R, it is intuitively clear that the effect on the matrix among these 5 factors is from large to small: tartaric acid, glycerol, sodium polyacrylate, aluminum glycinate and kaolin. It can be seen that kaolin has little effect on the matrix of the plaster, and the main effects on the matrix quality are glycerol and tartaric acid. From the analysis of the K value of the experimental result, the best process for preparing the plaster matrix is A ₁B₃C₃D₃E₂, namely the glycerin is taken in an amount of 7g, the sodium polyacrylate is 0.63g, the aluminum glycinate is 0.04g, the tartaric acid is 0.12g and the kaolin is 0.55g; further, the amount of glycerin to be used is preferably reduced.

Using the ratio of the amount of the matrix, the experimental results obtained after adding the ointment are shown in table 9:

TABLE 9 evaluation results of molded patches

Experimental results show that the appearance of the plaster is more uniform along with the increase of the heating and stirring time, and bubbles and particles are reduced; the heat resistance is obtained by taking the penetration condition as an evaluation standard, and the experimental result shows that the heat resistance has no relation with the stirring time of the plaster; in the initial adhesion test, the sliding distance of the coins is shortened along with the increase of the stirring time; in the holding power test, the time for which the test tool falls becomes longer as the stirring time becomes longer.

1.2.4 Discussion

In the emplastrum, the formulation and proportion of the matrix and the selection of the matrix materials are key to the quality of the gel emplastrum, and multiple experiments are needed to be carried out for exploration. It is evident from the experiment that the skin following property of the paste is reduced and the degree of penetration is increased with increasing glycerol amount, and that the K value obtained in 16 experiments shows that the score is increased with decreasing glycerol amount, and that the optimum amount in the experiment is 7g, but the smaller the glycerol amount is, the better the possibility is also present. With the increase of the dosage of the sodium polyacrylate, the total score is provided with a trace which is firstly increased and then decreased, so that a peak value is generated, and under the proportion, the dosage of the sodium polyacrylate is optimal to about 0.63g, and the aluminum glycinate, the tartaric acid and the kaolin are the same as the sodium polyacrylate, so that the dosage is better to determine the value. However, the effect of the amount of tartaric acid on the molding of the plaster is large, and the literature indicates that the paste has better viscosity when the proportion of the crosslinking regulator and the Ph regulator is close, and has moderate crosslinking speed, for example, the proportion of aluminum glycyrrhetate and tartaric acid is the same, so that the optimal preparation process of the experiment can be ensured only by adjusting the experiment and the retraction proportion.

On the basis of single factor investigation, the uniform experimental design method is used, skin following property, adhesiveness, shaping property and membrane residue are used as evaluation indexes of the breast-calming gel paste, the dosage of a matrix prescription is improved, and the optimized mass ratio of the matrix prescription is glycerin: pure water: sodium polyacrylate: al (OH) ₃: tartaric acid is 0.6475:0.1712:0.1446:0.0163:0.0068. in this experiment, it was shown that the proportion of glycerol used was small.

The heating and stirring time period has great influence on the plaster, and experimental results show that the longer the heating and stirring time period is, the better the appearance property is, the more uniform, the less bubbles and the less particles are, the initial adhesion and the lasting adhesion are also increased, and the longer the heating and stirring time period is, the better the experimental final result is.

The existing gel plaster evaluation indexes such as sensory evaluation indexes comprise appearance property, film residue, skin following property, penetration degree and the like. Although a certain guiding value exists, the subjective evaluation has large difference and multiple factors, and the experimental result is not strictly and reliably analyzed. Therefore, the experiment adds objective evaluation of initial adhesion and holding adhesion, so that the experiment has more data reliability and objective rules of the experiment are easier to obtain. In addition, since the effect of the amount of glycerol and the stirring time period on the experiment does not have a peak, there is a room for exploratory use, and attention is paid to the study in the future.

1.3 Content determination

1.3.1 Preparation of sample solution

Taking 3.12g of extracted ointment and 0.94g of formed plaster, respectively placing the extracted ointment and the formed plaster in a 100mL beaker, respectively adding 15mL of methanol and 10mL of methanol, placing the mixture on an ultrasonic cleaner for ultrasonic treatment, and fully dissolving the mixture.

1.1 Preparation of Standard solution

Taking 510 mL clean measuring flasks, placing 5mg oleanolic acid standard in the first measuring flask, adding 5mL methanol, shaking uniformly, dissolving, and adding methanol to fix volume to scale marks; adding 5mL of solution from the first measuring flask into the second measuring flask, fixing the volume to the scale mark, and uniformly mixing; adding 5mL of solution from the second measuring flask into the third measuring flask, adding methanol to fix the volume to the scale mark, and fully and uniformly mixing; and continuing the subsequent operation, wherein the 5 measuring flasks have solutions with certain concentrations, and the solution concentrations of the No. 1-5 measuring flasks are respectively 0.5mg/mL,0.25mg/mL,0.125mg/mL,0.0625mg/mL and 0.03125mg/mL, so as to obtain reference substance solutions with different concentrations of 5.

1.3.2 High Performance liquid phase method content determination

(1) Preparation of sample injection liquid

The sample solution and the standard solution are taken by a 5mL syringe, filtered by a microporous filter membrane and placed in a high-liquid small bottle, and the volume of the solution is about 1-1.5 mL.

(2) Chromatographic conditions

Column GH0525046C18A (4.6 mm. Times.250 mm,5 μm); mobile phase: acetonitrile: water=90:10; sample injection amount: 10. Mu.L; column temperature: 30 ℃; wavelength: 205nm; flow rate: 1.0mL/min.

1.3.3 Results

(1) Reference substance and test sample spectrogram

The spectrum of the obtained reference substance is shown in figure 4, oleanolic acid is the maximum peak in the graph, the retention time is 10.395min, the peak area is 3899.65186 mAU.s, and the concentration of oleanolic acid is 0.5mg/mL.

As shown in fig. 5, the retention time of oleanolic acid in sample No. 1 was 10.396min, and the peak area was 838.33316 mau×s, which corresponds to the retention time in the control.

As shown in fig. 6, the retention time of oleanolic acid in sample No. 2 was 10.541min, and the peak area was 103.327 mau x s, corresponding to the retention time in the control.

(2) Data processing

The peak areas obtained by measuring the high performance liquid phase at 5 different concentrations of the reference substance are shown in Table 10, the concentration of the designed solution is on the abscissa, the peak area is on the ordinate, and the result is shown in FIG. 7, so that the standard curve of the oleanolic acid content is obtained.

Table 10 results of high Performance liquid phase measurement of oleanolic acid Standard

As a result, R ² =0.9999, the reliability of the standard curve is high, the peak area corresponding to the retention time in the test sample is substituted into the standard curve y=7764.9x+19.658 obtained as described above, and the concentration and content of oleanolic acid in the test sample are calculated, and the results are shown in table 11:

TABLE 11 oleanolic acid content in test samples

The results show that the ointment which is not prepared into the preparation form contains 0.05% of oleanolic acid, and the oleanolic acid content in the ointment after the preparation form is prepared is 0.03%, so that certain loss exists in the process of preparing the ointment into the preparation form, but the influence of the floating is small from the aspect of loss, the ointment prepared into the preparation form probably has lower oleanolic acid content than the ointment which is directly extracted due to factors such as insufficient uniformity, insufficient dissolution to methanol and the like, and therefore, the average value is more accurate, and the formed emplastrum contains 0.04% of oleanolic acid serving as the ointment as an evaluation standard.

2. Pharmacodynamic study

2.1 Experimental materials

2.1.1 Experimental drug

Arthralgia formula: weighing 12g of prepared common monkshood mother root, 6g of asarum, 9g of swordlike atractylodes rhizome, 9g of pubescent angelica root, 9g of twotooth achyranthes root, 12g of whole Chinese angelica, 30g of yam, 30g of obscured homalomena rhizome, 30g of cortex schizophragmatis integrifolii radicis, 18g of Chinese clematis, 15g of pine node, 10g of red graminaceous, 12g of Chinese taxillus twig, 12g of east Asian tree fern rhizome, 12g of cortex acanthopanacis, 15g of suberect spatholobus stem, 12g of common burreed rhizome and 12g of zedoary, crushing into coarse powder, soaking the coarse powder in 15 times of 60% ethanol for 24h, reflux-extracting for 3h, filtering to obtain filtrate, removing solvents such as ethanol in the filtrate by using a rotary evaporator, and finally drying the extract in an oven at 70 ℃ to obtain the extract for experiments.

Aspirin enteric-coated tablet, yunnan white drug powder group Co., ltd., lot: ZJA2202. Specification of: 25 mg/tablet, national drug standard: H53021845. the usage amount is as follows: orally taken, 2-4 tablets at a time, once a day.

Prednisone acetate tablet, zhejiang Xian according to pharmaceutical Co., ltd., lot number: LA22503. Specification of: 5 mg/tablet, national drug standard: H33021207. the usage amount is as follows: orally taken, 1 tablet at a time, twice a day.

Glacial acetic acid (analytically pure), dujinshan chemical reagent limited, lot number: 20221006, specification: 500 mL/bottle.

Xylene (analytically pure), chongqing Ganchuandong chemical Co., ltd., specification: 500 mL/bottle.

2.1.2 Laboratory animals and feeds

SPF-grade mice weighing 19-23g, supplied by the company Si Bei Fu (Beijing) Biotechnology Co., ltd., license number: SCXK (Beijing) 2019-0010. Adaptive feeding: all mice were used after 3 days of adaptive feeding at the university of Guizhou university pharmaceutical college laboratory animal center.

Feed and padding: complete pellet feed, corncob litter, are all provided by Chongqing Watson biotechnology Co.

Feeding environment: the SPF class animal houses 501 and 503 of Guizhou university pharmacy have clean and quiet indoor environment, are equipped with an aluminum frame plate type rough air filter and an indoor ventilation system provided by Suzhou Huatai air filter Limited company, and have humidity of 30-40% and temperature of 22-25 ℃. Experimental animal use license number: SYXK (noble) 2022-0004. The mice are fed in separate cages and are fed with complete feed, and the natural mineral water of the farmer mountain spring is freely drunk.

2.1.3 Dose selection

According to the dose setting arthralgia prescription (4 times equivalent amount) and low (equivalent amount) 2 dose groups clinically used by the test drug (crude drug) adult, an aspirin group and a prednisone acetate group are established in a positive control group, the equivalent dose conversion is calculated according to a kilogram body weight dose conversion coefficient method, and the body weight of the adult is calculated according to 50 kg.

2.2 Experimental methods

2.2.1 Analgesic action-writhing method

SPF-grade mice weighing 18-22g were randomly divided into acetic acid blank group, aspirin group (0.72 g.kg ^-1·d^-1), low dose group of arthralgia prescription (1.75 g.kg ^-1·d^-1), high dose group of arthralgia prescription (7 g.kg ^-1·d^-1), and 12 animals each. The blank group was given equal amounts of distilled water and the experimental group was filled with aspirin and different doses of the pain relieving prescription solution, respectively. Once a day, and administered for 7 days. After 1.5h of last dose, each mouse was intraperitoneally injected with 0.6% acetic acid, 0.2 mL/mouse. The number of torsion reactions (abdominal contraction indent, extension hind limb, buttocks elevation, creep) after 15min of acetic acid solution injection was observed. The number of twists of mice in each dosing group was compared to the untreated model group using a t-test to determine if the experimental results were statistically significant.

2.2.2 Anti-inflammatory Activity-xylene-induced ear swelling method in mice

SPF-grade mice weighing 18-22g were randomly divided into 48 groups of xylene blank group, prednisone acetate group (0.09 g.kg ^-1·d^-1), low dose group of arthralgia prescription (1.75 g.kg ^-1·d^-1), and high dose group of arthralgia prescription (7 g.kg ^-1·d^-1), each group of 12. The blank group was given equal amount of distilled water, and the experimental group was respectively filled with prednisone acetate and arthralgia prescription solutions of different concentrations. Once a day, and administered for 7 days. After 1.5h of last dose, xylene (0.02 mL/mouse) was uniformly smeared on the front and back sides of the left ear of the mouse to cause inflammation. Then, after 25 minutes, the mice were suddenly killed, and round lugs were punched on the same parts of both ears of the mice by a 6mm punch and weighed. The weight difference between the left and right ears was calculated. The results of the experiments were statistically significant using a t-test to compare the extent of auricle swelling in each of the mice in the dosing group with the untreated model group.

2.3 Statistical treatment

The method for calculating the pain inhibition rate of acetic acid torsion experiment comprises the following steps: pain inhibition = (number of vehicle responses in blank group-number of vehicle responses in administration group)/number of vehicle responses in blank group x 100%. The swelling degree is obtained by subtracting the weight of the left ear from the weight of the right ear of each mouse. Experimental results are expressed as mean ± standard deviation, experimental data are statistically analyzed with SPSS27.0, group comparisons are tested using one-way ANOVA, analysis of variance is tested with F.

2.4 Results and discussion

2.4.1 Experimental results

Effects of arthralgia prescription on acetic acid on the number of times the abdominal cavity of mice is twisted: the number of writhing times of mice in the aspirin group and the arthralgia prescription high-dose group is obviously reduced, and the aspirin group and the arthralgia prescription high-dose group have statistical significance (p is less than 0.05) compared with a blank control group. The high-dose group of the arthralgia prescription can effectively relieve pain caused by acetic acid on the abdominal cavity of the mice, and the arthralgia prescription is indicated to have good analgesic effect. Wherein, the pain relieving effect of the high-dose group of the arthralgia prescription is obviously better than that of the low-dose group. The results are shown in Table 12.

Table 12 influence of arthralgia prescription on the number of writhing times in acetic acid-induced peritonitis mice (n=12, x±s)

Note that: a p < 0.05 compared with the blank group

Effect of pain prescription on xylene resulting in the extent of ear swelling in mice: experimental results show that the low-dose and high-dose group of the arthralgia prescription and the prednisone acetate group have obvious inhibition effect on ear swelling of mice caused by dimethylbenzene, can reduce the ear swelling of the mice, and indicate that the arthralgia prescription has good anti-inflammatory effect. Each dosing group had statistical significance (p < 0.05) by comparison to the blank. The swelling degree of the high-dose group of the arthralgia prescription is obviously smaller than that of the low-dose group, which indicates that the anti-inflammatory effect of the high-dose group is better than that of the low-dose group. The results are shown in Table 13.

Table 13 effect of pain management on xylene-induced ear swelling in mice (n=12, x±s)

Group of	Dosage (g, kg ^-1)	Swelling degree
			Blank control group	-	3.8±1.5
Aspirin group	0.09	1.7±0.6^a
			Low dosage group of arthralgia-relieving prescription	1.75	2.2±0.7^a
High-dose group of arthralgia-relieving prescription	7.00	1.7±1.1^a

Note that: ^a p < 0.05 compared with the blank group

2.4.2 Discussion

The Olibanum contains terpene compounds such as beta-Gu Xi, alpha-pinene, beta-pinene, etc., and has fresh, aromatic and sweet smell; the myrrh contains phenolic compounds such as bisabolol, bisabolol oil, etc., so that the myrrh has woody and sweet smell. The two traditional Chinese medicines are used as the compound spice, so that the taste and smell of the compound can be improved, and the compound has the effects of activating blood, relaxing muscles and tendons and relieving pain.

Chuan Wu has the actions of dispelling cold and dampness, and relieving arthralgia due to wind-dampness and blood. "(" Pearl sac ") contains a large amount of aconite alkaloids, and researches show that aconite alkaloids can affect spinal cord microglia to release dynorphin so as to act on k-opioid receptors to produce analgesic effect. Coumarin component contained in radix Angelicae Pubescentis has conjugated double bond structure, so as to have obvious antiinflammatory and analgesic effects, wherein dihydroimperatorin (dihydroimperatorin angelate) can block calcium channel, and can obviously inhibit prolactin induced by thyroid stimulating hormone releasing hormone. Volatile oil in angelica can inhibit edema and exudation of early inflammation, can inhibit tissue proliferation and granulation tissue formation of late inflammation, and has obvious analgesic and anti-inflammatory activity. The A3 active site of Angelica sinensis (neutral, non-phenolic site extracted from Angelica sinensis total volatile oil by CO2 supercritical method) can obviously inhibit mouse auricle swelling caused by xylene and inhibit rat uterus COX-2mRNA and protein expression induced by LPS (lipopolysaccharide) in a dose-dependent manner, which indicates that the analgesic effect is possibly related to the ability of the extract to inhibit COX-2mRNA and protein expression. But Chinese angelica can also be used as food materials in life, belongs to medicine and food homologous traditional Chinese medicines, and can enrich blood, promote blood circulation, regulate menstruation and relieve pain, so that the extract of Chinese angelica is also used as a product raw material in medicine and health care industries. Beta-eucalyptol, one of the major components of rhizoma Atractylodis, can inhibit receptor-interacting protein-2 expression and caspase-1 activation by blocking activation of mast cell p38 mitogen-activated protein kinase and NF-kB, and produce mast cell mediated inflammatory responses by inhibiting IL-6 expression by phorbol ester plus calcium ionophore a23187 human mast cell. With the continuous development of modern technology, the intensive research and clinical verification of traditional Chinese medicine compound will further perfect the system of treating rheumatism by traditional Chinese medicine, and have better curative effect, reduce pain of patients and improve life quality of patients. Meanwhile, in the aspect of combining traditional Chinese medicine and western medicine and personalized treatment, the traditional Chinese medicine compound is expected to become one of important RA treatment means.

Claims

1. A gel emplastrum for treating arthralgia, which is characterized in that: the medicinal active ingredients of the composition are calculated according to the weight components: is prepared from prepared Sichuan aconite root 90-150 parts, asarum herb 40-80 parts, atractylodes rhizome 60-120 parts, pubescent angelica root 60-120 parts, achyranthes root 60-120 parts, chinese angelica root 90-150 parts, dragon's bone 200-400 parts, homalomena rhizome 200-400 parts, schizophragma integrifolium 200-400 parts, clematis chinensis 130-230 parts, pine node 100-200 parts, red graminea 100-200 parts, loranthus mulberry mistletoe 90-150 parts, cibotium barometz 90-150 parts, acanthopanax bark 90-150 parts, spatholobus stem 100-200 parts, burreed tuber 90-150 parts, zedoary 90-150 parts;

(1) Weighing the medicinal materials according to the prescription proportion, crushing the medicinal materials into coarse powder, accurately weighing 15-20g of the total mass of the medicinal materials by an electronic analytical balance, soaking the medicinal materials in 12-18 times of ethanol for 18-30h, extracting the medicinal materials under reflux for 2-4h, filtering, and drying the filtrate at 60-80 ℃ to obtain a traditional Chinese medicine ointment for later use;

2. The gel patch for treating arthralgia according to claim 1, wherein: the medicinal active ingredients of the composition are calculated according to the weight components: is prepared from 100-140 parts of prepared common monkshood mother root, 50-70 parts of asarum, 70-110 parts of rhizoma atractylodis, 70-110 parts of radix angelicae pubescentis, 70-110 parts of achyranthes bidentata, 100-140 parts of whole angelica sinensis, 250-350 parts of Ningpo Yam rhizome, 250-350 parts of obscured homalomena rhizome, 250-350 parts of cortex schizophragmatis integrifolii radicis, 150-210 parts of radix clematidis, 120-180 parts of pine node, 80-120 parts of red graminea, 100-140 parts of mistletoe, 100-140 parts of rhizoma cibotii, 100-140 parts of cortex acanthopanacis, 120-180 parts of suberect spatholobus stem, 100-140 parts of rhizoma sparganii and 100-140 parts of rhizoma curcumae.

3. The gel patch for treating arthralgia as set forth in claim 2, wherein: the medicinal active ingredients of the composition are calculated according to the weight components: is prepared from prepared Sichuan aconite root 120 parts, asarum herb 60 parts, atractylodes rhizome 90 parts, pubescent angelica root 90 parts, achyranthes root 90 parts, chinese angelica root 120 parts, ningpo Yam rhizome 300 parts, homalomena rhizome 300 parts, dried rhizome of rehmannia 300 parts, clematis chinensis 180 parts, pine node 150 parts, red rice 100 parts, loranthus mulberry mistletoe 120 parts, cibotium barometz 120 parts, cortex acanthopanacis 120 parts, spatholobus stem 150 parts, burreed tuber 120 parts, zedoary 120 parts.

4. A method for preparing a gel patch for the treatment of pain according to any one of claims 1 to 3, wherein: the preparation method of the gel emplastrum for treating arthralgia comprises the following steps:

5. The method for preparing the gel patch for treating arthralgia as set forth in claim 4, wherein: in the step (1), the medicinal materials are weighed according to the prescription proportion, crushed into coarse materials, the total mass of the medicinal materials is accurately weighed to be 17.1g by an electronic analytical balance, the medicinal materials are soaked for 24 hours by 15 times of ethanol, the reflux extraction is carried out for 3 hours, the filtration is carried out, and the filtrate is dried at 70 ℃ to obtain the traditional Chinese medicine ointment for standby.

6. The method for preparing the gel patch for treating arthralgia as set forth in claim 4, wherein: in the step (2), 0.63g of sodium polyacrylate, 0.55g of kaolin and 7g of glycerin are accurately weighed as phase A for later use.

7. The method for preparing the gel patch for treating arthralgia as set forth in claim 4, wherein: in the step (3), 0.04g of aluminum glycinate, 12g of tartaric acid and 0.3g of menthol are accurately weighed as a B phase for standby.

8. The method for preparing the gel patch for treating arthralgia as set forth in claim 4, wherein: in the step (4), the phase A is heated on a water bath kettle at 70 ℃ and is rapidly stirred for 7min, the phase B is added into the phase A, and the rapid stirring is continued for 7min to obtain a gel matrix for later use.

9. The method for preparing the gel patch for treating arthralgia as set forth in claim 4, wherein: in the step (5), the traditional Chinese medicine ointment is added into the gel matrix, stirred for 25min, the obtained ointment is paved on non-woven fabrics with the length of 8cm and the length of 12cm, and the non-woven fabrics are placed in a shade place for cooling and solidifying to obtain the gel emplastrum.