Pharmaceutical composition with analgesic effect as well as preparation method and application thereof

Abstract

The invention provides a pharmaceutical composition with an analgesic effect. The pharmaceutical composition is an external medicament prepared from the following raw material medicines in parts by weight: 10 to 16 parts of teasel root, 2.4 to 3.6 parts of dragon's blood, 8 to 12 parts of safflower, 9.6 to 14.4 parts of myrrh, 9.6 to 14.4 parts of ligusticum wallichii, 9.6 to 14.4 parts of radix angelicae, 9.6 to 14.4 parts of notopterygium root, 8 to 12 parts of clove, 8 to 12 parts of beautiful sweetgum fruit, 0.64 to 0.96 part of pepper, 2.4 to 3.6 parts of lucid ganoderma, 112 to 168 parts of pepper and 0.8 to 1.2 parts of musk. The invention also provides a preparation method and application of the pharmaceutical composition. The medicine disclosed by the invention is precise and appropriate in raw material formula compatibility, is used for treating pain, is clear and controllable in medicine effect, and provides a new clinical medication choice.

Description

TECHNICAL FIELD

[0001] The present application relates to a pharmaceutical composition with analgesic effect and its preparation method and use, belonging to the field of medicine. BACKGROUND

[0002] In recent years, pain is one of the most common complaints and main symptoms in patients of various clinical departments. Pain syndrome is a kind of disease syndrome with pain as the main clinical manifestation. Pain syndrome involves a wide range of clinical disciplines and can be seen in common and difficult diseases of internal medicine, surgery, gynecology, pediatrics, orthopedics, oncology, and neurology. The disease involves the whole body from head to foot. Chinese medicine has a long history of understanding and treating pain syndrome, with many advantages. Not only is the theory unique, but the treatment range is also extremely wide, with rich experience and numerous simple and effective treatments. However, according to current literature reports, the TCM syndrome of pain lacks standardized criteria and is in a state of low-level repetition and confusion, and a comprehensive and systematic understanding has not yet been formed. For example, Application No. 200610045476.2, entitled "A liniment for treating acute and chronic soft tissue injuries of qi stagnation and blood stasis type and its preparation method," discloses a liniment for treating acute and chronic soft tissue injuries of qi stagnation and blood stasis type and its preparation method, which is composed of the following raw materials: Chuanxiong 45-73, Honghua 26-50, Danggui 15-33, Ru Xiang 15-33, Muyan 15-33, Xihonghua 0.5-1.5, Qianghuo 26-50, Duhuo 26-50, Huajiao 26-50, Shanzhi 15-33, Zicao 15-33, Bocengqia 15-33, Dingxiang 15-33, Yuanhu 15-33, Rucui 15-33, Bingpian 13-23, Longxuejie 2.5-5.5. Application No. 202210041361.5, entitled "A multifunctional external medicine for treating sprains and rheumatism made of traditional Chinese medicine," discloses a multifunctional external medicine for treating sprains and rheumatism made of traditional Chinese medicine. The raw materials include Jixueteng, Suomu, Maqianzi, Honghua, Dahuang, Niuxi, Taoren, Zelan, Mahuang, Qianghuo, Fangfeng, Xixin, Baizhi, Cang'ersi, Bohe, Duhuo, Weilingxian, Caowu, Shenzhengcaocao, Qinjiu, Fangyi, Wujiaopi, Gouji, Muxiang, Chenxiang, Huangbai, Shengdi, Mudanpi, Chishao, Jigucao, Chuanxiong, Jianghuang, Yannuxie, Ruxiang, Gushubu, Tuobichong, Zhenxingtong, Sanlieng, Quanxie, Huangqi, Gancao, Tuisi, Danggui, Wweishizi, Dingxiang, Xiaohuixiang, Echa, Ganla jiao, Huajiao, Tian'nansheng, Bingpian, Zhan'gong, etc. The multifunctional external medicine for treating sprains and rheumatism has antibacterial efficacy, and is highly concentrated white liquor. Therefore, it has the effects of promoting blood circulation to remove blood stasis, rapidly relieving swelling and pain, rapidly promoting tissue regeneration and skin regeneration, and dispelling wind and dampness and resolving nodes.Application No. 202110378776.7, Invention Name: A Traditional Chinese Medicine Composition for Treating Sprains and Strains and Its Preparation Method, relates to a traditional Chinese medicine composition for treating sprains and strains and its preparation method, which is composed of the following raw materials by weight: Zanthoxylum bungeanum 10-20 parts, capsaicin 5-10 parts, milk 5-20 parts, vaseline 8-30 parts, large umbrella 10-30 parts, lotus leaf 20-40 parts, camphor 1-5 parts, dandelion 10-50 parts, summer 3-20 parts, Radix et Rhizoma Breviscae 10-25 parts, mugwort leaf 1-10 parts, safflower 1-10 parts, white mustard seed 3-15 parts, cassia twig 2-12 parts and radix et rhizoma aconiti 10-30 parts. The traditional Chinese medicine composition combines various drugs to have the effects of activating blood and resolving stasis, reducing swelling and relieving pain, so as to treat symptoms such as blood stasis and swelling pain, qi-blood disharmony and meridian obstruction caused by sprains and strains.

[0003] Due to the complex pathogenesis and pathology of painful syndromes, different painful syndromes have obvious differences in drug efficacy based on the compatibility of traditional Chinese medicine theory. SUMMARY

[0004] The present application provides a new pharmaceutical composition with analgesic effect. The present application also provides a preparation method and use of the pharmaceutical composition.

[0005] The present application also provides a pharmaceutical composition with analgesic effect, which is an external preparation prepared from raw medicinal materials in the following weight ratio:

[0006] Radix Dipsaci 10-16 parts, blood 2.4-3.6 parts, safflower 8-12 parts, myrrh 9.6-14.4 parts, Chuanxiong 9.6-14.4 parts, Baizhi 9.6-14.4 parts, Notopterygium 9.6-14.4 parts, clove 8-12 parts, lalun 8-12 parts, Zanthoxylum bungeanum 0.64-0.96 parts, Ganoderma lucidum 2.4-3.6 parts, pepper 112-168 parts, musk 0.8-1.2 parts.

[0007] Further preferably, it is an external preparation prepared from raw medicinal materials in the following weight ratio:

[0008] Radix Dipsaci 13 parts, blood 3 parts, safflower 10 parts, myrrh 12 parts, Chuanxiong 12 parts, Baizhi 12 parts, Notopterygium 12 parts, clove 10 parts, lalun 10 parts, Zanthoxylum bungeanum 0.8 parts, Ganoderma lucidum 3 parts, pepper 140 parts, musk 0.1 parts.

[0009] The pharmaceutical composition of the present application is an external preparation prepared from the raw medicinal material of the raw medicinal powder, water or organic solvent extract as the active ingredient, and the addition of excipients or auxiliary ingredients; the organic solvent is ethanol; the concentration of the ethanol is 50-75%.

[0010] Further preferably, the ethanol concentration is 60%; and the pharmaceutical preparation is a plaster, a tincture, a spray, a liniment, a cream, a lotion, or an essence.

[0011] The present application also provides a preparation method of the pharmaceutical composition, which comprises the following steps:

[0012] a. weighing each raw material;

[0013] b. powdering the raw materials or extracting them with water or an organic solvent, and then adding excipients or auxiliary ingredients to prepare the external preparation.

[0014] The present application provides the use of the pharmaceutical composition in the preparation of an external medicine for warming the meridians, dredging the collaterals, relieving pain, dispelling wind and dampness, and removing cold, activating blood circulation to remove blood stasis.

[0015] The pharmaceutical composition of the present application has the effects of warming the meridians, dredging the collaterals, relieving pain, dispelling wind and dampness, and removing cold, activating blood circulation to remove blood stasis. It is mainly used for treating the accumulation of wind, cold and dampness in the muscles and joints, old injuries and overuse of the bones and joints, and the invasion of wind, cold and dampness in the bones and joints. The main ingredient is Dipsacus asper. Dipsacus asper can strengthen the muscles and bones, and treat fractures. It is mainly used for treating the accumulation of wind, cold and dampness in the muscles and joints, old injuries and overuse of the bones and joints, and the invasion of wind, cold and dampness in the bones and joints. Cloves, Sichuan pepper and chili peppers are the secondary ingredients. Cloves dispel cold and relieve pain, Sichuan pepper dispels cold and dredges the collaterals, and chili peppers warm the meridians and relieve pain. The three ingredients work together to warm the meridians, dredge the collaterals, and relieve pain. Sichuan pepper, Sichuan aloe and Qianghuo are the auxiliary ingredients. Sichuan pepper activates blood circulation, dispels wind and relieves pain, Sichuan aloe dispels wind and dampness, dredges the collaterals, and relieves pain, and Qianghuo dispels cold and wind, dispels dampness, and relieves pain. The three ingredients work together to dispel wind and dampness. Blood stasis, safflower, myrrh, luffa, ganoderma lucidum and musk are the auxiliary ingredients. The combination of the six ingredients makes the various ingredients of the medicine penetrate the skin, vessels, flesh, tendons and bones, and achieve the effect of activating blood circulation to remove blood stasis. The ingredients of the medicine are well matched, and the medicine has clear effects and can be controlled. It provides a new choice for clinical treatment. DETAILED DESCRIPTION

[0016] Example 1: Preparation method of the pharmaceutical composition A of the present application

[0017] Weigh the raw materials: Dipsacus asper 13g, cloves 10g, Sichuan pepper 0.8g, ganoderma lucidum 3g, and chili peppers 140g. Add 50% ethanol for extraction, and then concentrate to 3g of raw medicine per ml to obtain a liniment.

[0018] Example 2: Preparation of the pharmaceutical composition B of the present application

[0019] Take the raw materials: Chuanxiong 12g, Notopterygium 12g, Sanguis Draconis 3g, safflower 10g, myrrh 12g, rue 10g, musk 0.1g, add 50% ethanol extraction, and then concentrate to 3g of raw medicine / ml, to get the liniment.

[0020] Example 3 Preparation of the liniment of the medicine of the present application (hereinafter referred to as: the medicine composition C group of the present application)

[0021] Continue 13g, Sanguis Draconis 3g, safflower 10g, myrrh 12g, Chuanxiong 12g, Bai Zhi 12g, Notopterygium 12g, clove 10g, rue 10g, Zanthoxylum 0.8g, Ganoderma 3g, chili 140g, musk 0.1g, mix, add 50% ethanol extraction, and then concentrate to 3g of raw medicine / ml, to get the liniment.

[0022] Example 4 Preparation of the spray of the medicine of the present application

[0023] Take the raw materials: Continue 10g, Sanguis Draconis 2.4g, safflower 8g, myrrh 9.6g, Chuanxiong 9.6g, Bai Zhi 9.6g, Notopterygium 9.6g, clove 8g, rue 8g, Zanthoxylum 0.64g, Ganoderma 2.4g, chili 112g, musk 0.8g, add 95% ethanol extraction, and then concentrate the alcohol extract to extract, add water and other pharmaceutically acceptable matrix to prepare the spray.

[0024] Example 5 Preparation of the gel of the medicine of the present application

[0025] Take the raw materials: Continue 16g, Sanguis Draconis 3.6g, safflower 12g, myrrh 14.4g, Chuanxiong 14.4g, Bai Zhi 14.4g, Notopterygium 14.4g, clove 12g, rue 12g, Zanthoxylum 0.96g, Ganoderma 3.6g, chili 168g, musk 1.2g, add 80% ethanol extraction, and then concentrate the extract to extract, add the gel preparation adjuvant to prepare the gel.

[0026] The beneficial effects of the present application are demonstrated by the following pharmacodynamic test.

[0027] Test Example 1 Effect of the medicine of the present application on the acetic acid-induced writhing response in mice

[0028] 70 Kunming mice, half male and half female, weighing 18-22g, were shaved about 6cm on the abdomen 1d before the test 2 . According to the weight, they were randomly divided into 7 groups, 10 in each group. The model control group, the positive drug control group, the medicine composition A group of the present application, the medicine composition B group of the present application and the three dose groups of the test drug were set.

[0029] The positive drug control group applied Eucerin ointment to the depilation area of the animals with a cotton swab, with an average thickness of 1 mm per animal each time; the rest of the groups applied the extract respectively, 0.2 ml per animal each time, twice a day, for 4 consecutive days. The model control group applied distilled water. 30 min after the last administration, 0.7% acetic acid 0.2 ml per animal was injected intraperitoneally, the writhing latency of the mice was recorded, the writhing times of the animals within 15 min were observed, and the analgesic rate was calculated, analgesic rate (%) = (writhing times of the control group-writhing times of the administration group) / writhing times of the control group x 100%. The test results were statistically analyzed by SPSS22 software, and the data were expressed as mean ± standard deviation indicates that one-way ANOVA is performed, p<0.01 and p<0.05 indicate that there is a statistical difference between the two groups.

[0030] The writhing latency statistical results are shown in Table 1. Compared with the control group, the writhing latency of the mice in each administration group has a tendency to increase, among which the data of the high dose and large dose groups of composition A and composition C have statistical differences (p<0.05, p<0.01), and the effect of the pharmaceutical composition C of the present application is better than that of composition A and composition B. The latency time of the pharmaceutical composition C group of the present application increases with the increase of the dose, which is dose-dependent.

[0031] Table 1 Effect of the extract of the present application on the writhing latency of mice

[0032]

[0033] Note: compared with the control group, △ indicates P<0.05, △△ indicates P<0.01.

[0034] Test Example 2 Effect of the drug of the present application on the writhing times of mice within 15 min and analgesic rate

[0035] The writhing times statistical results of the mice in each group within 15 min are shown in Table 2. Compared with the model control group, the writhing times of the mice in each administration group have a tendency to decrease, among which the data of the high dose and large dose groups of the pharmaceutical composition A and the pharmaceutical composition C of the present application have statistical differences (p<0.05, p<0.01), and the effect of the pharmaceutical composition C of the present application is significantly better than that of composition A and composition B. The writhing times of the pharmaceutical composition C group of the present application decrease with the increase of the dose, and the analgesic rate increases, which is dose-dependent.

[0036] Table 2 Effect of the extract of the present application on the writhing times of mice within 15 min and analgesic rate

[0037]

[0038]

[0039] In summary, the medicine of the present application can prolong the latency of mouse writhing caused by acetic acid, reduce the number of writhing, and has obvious analgesic effect. Especially, the medicine composition C of the present application has obviously improved efficacy compared with the composition A and B at the same dosage.

[0040] Test Example 2: Typical case of clinical test of the medicine of the present application

[0041] The following clinical test case uses visual analogue scale (VAS) to evaluate the pain degree of the two groups of patients before and after treatment, wherein 0 point is no pain, 10 points is the most pain, and the higher the score, the more severe the pain. The liniment prepared in Example 3 is used for the subjects.

[0042] Case 1: Li, male, 49 years old, shoulder arthralgia (type of syndrome: cold-damp invasion type), local rubbing, 5g (original crude drug amount) each time, three times a day, use cycle of 21 days, VAS score from 7 points to 2 points.

[0043] Case 2: Yuan, female, 53 years old, knee arthralgia (type of syndrome: wind-cold-damp arthralgia type), local rubbing, 5g (original crude drug amount) each time, three times a day, use cycle of 14 days, VAS score from 5 points to 1-2 points.

[0044] Case 3: Wang, male, 41 years old, old fracture of ankle joint (type of syndrome: qi stagnation and blood stasis type), local rubbing, 5g (original crude drug amount) each time, three times a day, use cycle of 21 days, VAS score from 6 points to 2 points.

[0045] Case 4: Li, female, 52 years old, tennis elbow (type of syndrome: qi stagnation and blood stasis type), local rubbing, 3g (original crude drug amount) each time, three times a day, use cycle of 15 days, VAS score from 6 points to 2 points.

Claims

1. A pharmaceutical composition having analgesic effects, characterized in that: It is a topical medication prepared from the following raw materials in the indicated weight ratios: Dipsacus asperoides 10-16 parts, dragon's blood 2.4-3.6 parts, safflower 8-12 parts, myrrh 9.6-14.4 parts, chuanxiong rhizome 9.6-14.4 parts, angelica dahurica 9.6-14.4 parts, notopterygium root 9.6-14.4 parts, clove 8-12 parts, luffa fruit 8-12 parts, Sichuan pepper 0.64-0.96 parts, ganoderma lucidum 2.4-3.6 parts, chili pepper 112-168 parts, musk 0.8-1.2 parts.

2. The pharmaceutical composition according to claim 1, characterized in that: It is a topical medication prepared from the following raw materials in the indicated weight ratios: Dipsacus asperoides 13 parts, dragon's blood 3 parts, safflower 10 parts, myrrh 12 parts, chuanxiong rhizome 12 parts, angelica dahurica 12 parts, notopterygium root 12 parts, clove 10 parts, luffa fruit 10 parts, Sichuan pepper 0.8 parts, lingzhi mushroom 3 parts, chili pepper 140 parts, musk 0.1 parts.

3. The pharmaceutical composition according to claim 1 or 2, characterized in that: It is a topical preparation made from the raw drug powder, water or organic solvent extract as active ingredients, and pharmaceutically acceptable excipients or auxiliary ingredients; the organic solvent is ethanol; the concentration of ethanol is 50-75%.

4. The pharmaceutical composition according to claim 3, characterized in that: The ethanol concentration is 60%; the pharmaceutical preparation is an ointment, tincture, spray, liniment, cream, lotion, or serum.

5. A method for preparing the pharmaceutical composition according to any one of claims 1-4, characterized in that: It includes the following steps: a. Weigh the raw materials according to the specified weight ratio; b. Topical preparations made by grinding the raw drug into powder or extracting it with water or organic solvents, and then adding pharmaceutically acceptable excipients or auxiliary ingredients.

6. The use of the pharmaceutical composition according to any one of claims 1-4 in the preparation of a topical medicine having the functions of warming the meridians and relieving pain, dispelling wind and dampness, dispersing cold, promoting qi and blood circulation and removing blood stasis.

7. The use according to claim 6, characterized in that: The aforementioned medicine is used to treat the stagnation of wind, cold, and dampness in the muscles, bones, and joints; old injuries and strains of bones and joints; or recurrence of wind, cold, and dampness invasion after bone and joint injuries.

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