CN113599484A

CN113599484A - Traditional Chinese medicine composition for treating pain and preparation method and application thereof

Info

Publication number: CN113599484A
Application number: CN202110900873.8A
Authority: CN
Inventors: 徐彬; 程建明; 金陵; 曹杰; 金栩强; 唐婷婷; 嵇晶; 郑云枫
Original assignee: Jiangsu Jinshidan Technology Co ltd
Current assignee: Jiangsu Jinshidan Technology Co ltd
Priority date: 2021-08-06
Filing date: 2021-08-06
Publication date: 2021-11-05

Abstract

A Chinese medicinal composition for treating pain is prepared from (by weight parts) caulis et folium piperis, radix Chloranthi Serrati 5-15, radix Trichosanthis Cucumeroidis 1-10, and Zingiberis rhizoma 1-10. The method provided by the invention has the advantages of simple and efficient process, safety, environmental protection and low requirement on equipment, and is beneficial to popularization in industrial production. Meanwhile, the traditional Chinese medicine composition disclosed by the invention can inhibit inflammation by reducing the levels of inflammatory factors and tumor necrosis factors in serum of an acetic acid analgesic model mouse, so that the analgesic effect is achieved.

Description

Traditional Chinese medicine composition for treating pain and preparation method and application thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating pain and a preparation method and application thereof.

Background

With the increasing social awareness of the influence of pain, the medical community is always dedicated to the research on the pain action mechanism and anti-pain drugs, and analgesia is an important task facing the medical community at present. The research level of the traditional Chinese medicine for treating the pain is continuously improved, and the traditional Chinese medicine for treating the pain plays a role of being not easy to wear out. The traditional Chinese medicine composition is part of excellent cultural achievements in China, and the effectiveness and the practicability of the traditional Chinese medicine composition play an important role in human health. The traditional Chinese medicine composition treats pain from multiple targets and multiple directions, has the characteristics of low price, small toxic and side effects, flexible medication and the like, and is concerned by the medical field.

At present, both the opioid and the non-steroidal drugs in clinical application have side effects of different degrees, such as nausea, vomiting, constipation and the like. The traditional Chinese medicine for treating pain needs to be taken for a long time, the compliance of patients is poor, and part of the traditional Chinese medicines for treating pain have slow response time and large dosage. Therefore, the development of the traditional Chinese medicine composition for treating pain has no great significance.

Disclosure of Invention

The technical problem to be solved is as follows: aiming at the problems existing in the prior art for treating pain, the invention provides a traditional Chinese medicine composition for treating pain and a preparation method and application thereof.

The technical scheme is as follows: a traditional Chinese medicine composition for treating pain is prepared from the following raw materials, by weight, 5-15 parts of Photinia serrulata (Piper wallichii (Miq.) hand-Mazz.), 5-15 parts of herba Chloranthi Henryi (Sieve viscoidea Franch.), 1-10 parts of radix Trichosanthis Cucumeroidis, and 1-10 parts of rhizoma Zingiberis (Zingier officinale Rosc.).

Preferably, the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5 parts of photinia serrulata, 5 parts of radix stephaniae tetrandrae, 3 parts of radix trichosanthis and 1 part of dried ginger.

The preparation method of the traditional Chinese medicine composition for treating pain comprises the following steps: weighing the raw materials, adding 70-90 wt.% ethanol 8-15 times the volume of the weighed raw materials, reflux-extracting for 1-3 times (1-3 h each time), filtering the extractive solution, and mixing the filtrates for use; decocting the residue in water for 1-3 times, extracting for 1-3 times, each for 1-3 hr, mixing the two filtrates, concentrating under reduced pressure, adding ethanol to 60-80 wt.%, standing, filtering, mixing the filtrate with the ethanol extractive solution, and concentrating under reduced pressure.

Preferably, 85wt.% of ethanol is added into the weighed raw material medicines for reflux extraction for 1 time, the extraction time is 2 hours, and the mixture is filtered for standby; extracting the residue with water twice, the first time extracting with 8 times of water for 2 hr, the second time extracting with 6 times of water for 1 hr, filtering, mixing the filtrates, concentrating under reduced pressure, adding ethanol to 70wt.%, standing, filtering, mixing the filtrate with the ethanol extractive solution, and concentrating under reduced pressure until each ml of ethanol extractive solution is equal to 1.15-1.21g crude drug.

The application of the traditional Chinese medicine composition in preparing a medicine for treating pain.

Has the advantages that: the method provided by the invention has the advantages of simple and efficient process, safety, environmental protection and low requirement on equipment, and is beneficial to popularization in industrial production. The Chinese medicinal composition has pungent taste of the photinia serrulata and the dried ginger, pungent flavor can disperse energy, and the photinia serrulata is warm and smooth in dispersing and good at dispelling wind and relieving pain; gan Jiang is pungent, hot, dry and drastic, good at warming middle energizer and dispelling cold, so it is good at treating cold abdominal pain. When they are used together, they can strengthen the action of relieving pain. From the aspect of compatibility of traditional Chinese medicines, the photinia serrulata belongs to a medicine for dispelling rheumatism and has the functions of analgesia and anti-inflammation; the root of wampee belongs to the drugs for promoting diuresis and removing dampness, is good at treating the syndrome of stranguria caused by heat, and has obvious analgesic effect; the dried ginger belongs to a warming medicine and also has a certain analgesic effect. Clinical experience shows that the medicine pair of the photinia serrulata stem, the radix physochlainae and the dried ginger can enhance the analgesic effect. The caulis et folium piperis alkaloid components such as ethyl3',4',5' -trimethoxycinnamate, and Trachyone have antiinflammatory and antibacterial effects, and can be used for treating coronary heart disease and angina pectoris. The n-butanol part of the radix stephaniae tetrandrae has the effects of resisting inflammation and relieving pain, and is mainly used for stomachache, rheumatic pain, traumatic pain, sore and furuncle swelling and pain and the like in clinic. The radix Trichosanthis Cucumeroidis root protein has effects of resisting lung adenocarcinoma and nasopharyngeal carcinoma. Gingerol in Zingiberis rhizoma has analgesic and anti-inflammatory effects, and can be used for treating puerperal general pain and intestinal pain. The traditional Chinese medicine composition has better curative effect than a single medicine, can treat various pains such as dysmenorrheal, toothache, stomachache, arthralgia, labor pain, operation pain, cancer pain and the like, and has remarkable effect.

Drawings

FIG. 1 shows the analgesic effect of the Chinese medicinal composition on writhing response caused by acetic acid of mice (

n ═ 6); note comparison with model group<0.05，**p<0.01。

Detailed Description

The present invention is further described with reference to the following specific examples, which are only illustrative and not intended to limit the scope of the present invention. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.

Example 1 preparation of a Chinese medicinal composition for analgesic treatment and extract thereof

The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5 parts of photinia serrulata, 5 parts of radix stephaniae tetrandrae, 3 parts of radix trichosanthis and 1 part of dried ginger.

Preparing an extracting solution:

selecting ethanol concentration, ethanol dosage, extraction times and extraction time as investigation factors, adopting a single factor method and an orthogonal design method, taking the total content of effective components and the extraction rate as investigation indexes, and determining the optimal extraction process of the traditional Chinese medicine composition as follows:

(1) weighing the raw materials according to the weight parts

Adding 85wt.% ethanol into the weighed raw materials, reflux-extracting for 1 time for 2h, and filtering for later use; extracting the residue with water twice, the first time with 8 times of water for 2 hr, the second time with 6 times of water for 1 hr, filtering, mixing the filtrates, concentrating under reduced pressure, adding ethanol to 70wt.%, standing, filtering, mixing the filtrate with ethanol extractive solution, and concentrating under reduced pressure until each ml of ethanol extractive solution is equal to 1.15-1.21g crude drug.

Determination of chromatographic conditions

Selecting detection wavelength, chromatographic column type, mobile phase system and elution gradient as investigation factors, and determining optimum chromatographic conditions of the Chinese medicinal composition by HPLC method with peak area, peak-off time, and stable baseline as investigation indexes.

With Waters

C18 column (250X 4.6mm,5 μm) as filler; acetonitrile was used as mobile phase a, and 0.2% formic acid water was used as mobile phase B, and elution was performed as specified below; an ultraviolet detector; detection wavelength: 282 nm; flow rate: 1.0 mL/min; column temperature 25 deg.C

TABLE 1 gradient elution table for Chinese medicinal composition

EXAMPLE 2 preparation of a Chinese medicinal composition for the treatment of analgesia

The source of the medicinal materials is as follows:

photinia serrulata, batch number: 20190826, origin: guangxi; root of king melon, batch number: 20190919 origin: anhui), dried ginger (batch number: 190801 origin: yunnan luoping), roots of kola (batch number: 20190917 origin: yunnan), are provided by Jiangsu Jinshidan science and technology limited. The Chinese medicinal materials of the photinia serrulata, the wakame root, the royal melon root and the dried ginger are sequentially numbered A, B, C, D.

Taking appropriate amount of the Chinese medicinal composition, pulverizing, and sieving with a No. four sieve for use.

Preparing different traditional Chinese medicine compositions by adopting a negative control method:

traditional Chinese medicine composition 1 (powder ABCD): mixing 5 parts by weight of Photinia serrulata, 5 parts by weight of radix Chloranthi Henryi, 3 parts by weight of radix Trichosanthis Cucumeroidis and 1 part by weight of Zingiberis rhizoma, pulverizing, and sieving with a fourth sieve.

Traditional Chinese medicine composition 2 (powder ABC): mixing 5 parts by weight of Photinia serrulata, 5 parts by weight of herba Swertiae Mileensis and 3 parts by weight of radix Trichosanthis Cucumeroidis, pulverizing, and sieving with a fourth sieve.

Traditional Chinese medicine composition 3 (powder ABD): uniformly mixing 5 parts by weight of Photinia serrulata, 5 parts by weight of wampee roots and 1 part by weight of dried ginger, crushing, and sieving by a fourth sieve for later use.

Traditional Chinese medicine composition 4 (powder BCD): mixing 5 parts by weight of herba Orostachyos, 3 parts by weight of radix Trichosanthis Cucumeroidis and 1 part by weight of Zingiberis rhizoma, pulverizing, and sieving with a fourth sieve.

Traditional Chinese medicine composition 5 (powder ACD): 5 parts of photinia serrulata, 3 parts of radix trichosanthis and 1 part of dried ginger are uniformly mixed, crushed and sieved by a fourth sieve for standby.

Example 3 pharmacodynamic study of the herbs of the Chinese medicinal composition for relieving pain

1. Laboratory animal

SPF grade ICR mice, purchased from sbeft beijing biotechnology limited, license number: SCXK [ Jing ] 2019-.

2. Experimental drugs and reagents

2.1 Positive drugs: aspirin, bayer medicinal health limited, national drug standard J20140076.

2.2 molding agent: glacial acetic acid, 99.5% AR, available from shanghai alatin biochem technologies, was made up to 0.7% in distilled water for future use.

2.3 reagent: mouse tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) ELISA test kit, purchased from Nanjing winged snow Biotech, Inc.

2.4 receptor drugs:

the traditional Chinese medicine composition 1-5 prepared by the method of the embodiment 2 of the invention is prepared by 3.1mg/kg of powder ABCD group; powder ABC group is 3.0 mg/kg; powder ABD group 2.5 mg/kg; powder BCD group 2.1 mg/kg; powder ACD group 1.9mg/kg.

3. Experimental methods

3.1 animal grouping

48 mice were randomly divided into 8 groups of 6 mice each, i.e., group I (blank group), group II (model control group), group iii (positive control group), group IV (powder ABCD group), group V (powder BCD group), group VI (powder ACD group), group vii (powder BCD group), and group viii (powder ABC group). The mice are put in a clean plastic basket with proper size, are fed freely, are fed with tap water and are fed with standard feed, the padding is cleaned for 1 time every two days, the indoor temperature is maintained within the range of 18-22 ℃, the relative humidity is about 40.0 percent, the mice are placed on the window table, and the mice are used after being fed and observed for one week conventionally.

3.2 Prior to Experimental modeling

48 mice were acclimatized for one week to observe the presence or absence of abnormal appearance in all mice.

3.3 acetic acid induced writhing model in mice

The mice in the blank group are normally bred for seven days, and the mice in the model control group, the positive control group, the powder ABCD group, the powder BCD group, the powder ACD group, the powder BCD group and the powder ABC group are respectively administered with the drug of 0.1ml/10g by intragastric administration for 7 days continuously.

3.4 Molding

0.5h after the 7 th administration, 0.1ml/10g of 0.7% glacial acetic acid solution is injected into the abdominal cavity. The number of mice in each group was recorded within 30min after administration, as well as the response time to writhing response after gavage.

3.5 detection index

3.5.1 behavioral Observation indicators

The number of mice with writhing reaction within 30 minutes and the writhing frequency of each mouse (writhing index is such that the writhing inhibition rate of the mouse is calculated by taking the belly depression, the hip writhing, the body distortion or the hip extraction)

3.5.2 determination of inflammatory factors

All mice fundus venous blood was collected, centrifuged at 3500r/min at 4 ℃ for 10 minutes, and the supernatant was collected. ELISA method for detecting mouse tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) expression level and prostaglandin E2 (PGE)₂) Interleukin 1 beta (1L-1 beta).

4. The result of the detection

TABLE 2 analgesic Effect of the Chinese medicinal composition on writhing response caused by acetic acid of mice: (

n＝6)

Note that p <0.05, p <0.01, compared to model groups

The results of the analysis of the experimental results by using GraphPad Prism 8.3.0 statistical software are shown in the following figure 1, and the analgesic effect of the traditional Chinese medicine composition on the writhing reaction caused by the acetic acid of the mouse (

n＝6)

TABLE 3 Chinese medicinal composition for ICR mouse serum 1L-1 beta, TFN-alpha, IL-6, PEG₂Influence of content (

n＝8)

Note, p <0.05, p <0.01, p <0.001, compared to model groups

As can be seen from Table 2, the difference between the groups is obvious, and the drug groups can obviously prolong the torsion latency and reduce the torsion times compared with the model group, which indicates that the traditional Chinese medicine composition has better analgesic effect. The times of twisting are sequentially a model group, a powder ABC group, a powder BCD group, a powder ABD group, a powder ACD group, a powder ABCD group and a positive control group from large to small. And compared with a model group (normal saline control group), the powder ABCD group, the powder ABD group and the powder ACD group have significant differences. The positive control aspirin group had a highly significant difference compared to the model group (normal saline control group).

As can be seen from fig. 1, the number of writhing of the traditional Chinese medicine composition (compound powder ABCD group) is similar to that of the positive medicine, which indicates that the analgesic effect of the traditional Chinese medicine composition is significant. Negative control design test shows that the Chinese medicinal composition has analgesic effect. The analgesic activity is as follows from big to small: the powder ABCD, ACD, ABD, BCD and ABC have the best analgesic activity, namely the analgesic activity of the medicinal material of the root of wakame, the medicinal material of the root of Chinese photinia, and the analgesic activity of the medicinal materials of the dried ginger and the root of the king melon are similar.

As can be seen from Table 3, compared with the blank group, the contents of inflammatory factors 1L-1 beta, TFN-alpha and IL-6 in the serum of the model group mice are very significantly different (P is less than 0.001), and PEG in the serum of the mice is very significantly different (PEG is less than 0.001)₂The content increase is obviously different from that of a blank group (P is less than 0.05). Compared with the model group, the traditional Chinese medicine composition group can remarkably reduce 1L-1 beta, TFN-alpha, IL-6 and PEG in serum₂The content and the reduction range except IL-6 are obviously larger than that of an aspirin positive control group. The experimental result indicates that the anti-inflammatory and analgesic mechanism of the traditional Chinese medicine composition group is possible to inhibit proinflammatory factors 1L-1 beta, TFN-alpha and PEG₂Release is relevant.

The above tests are carried out for facilitating understanding of the raw material medicaments and the drug effect in the invention: the invention adopts an acetic acid writhing method with strong sensitivity and high stability to establish an animal model, and the mice have obvious symptoms of abdominal depression, hip wriggling, body distortion and the like. Compared with the model group, each drug group can obviously prolong the torsion latency and reduce the torsion times compared with the model group, and 1L-1 beta, TFN-alpha, IL-6 and PEG in serum₂The contents of the compounds are all obviously reduced, which shows that the traditional Chinese medicine composition inhibits the generation of inflammation by reducing the levels of inflammatory factors and tumor necrosis factors in the serum of an acetic acid pain-relieving model mouse so as to achieve the effect of relieving pain.

Example 4 provides a capsule of a traditional Chinese medicine composition ("JSD analgesic capsule"), consisting of:

5-15 parts of photinia serrulata, 5-15 parts of radix physochlainae, 3 parts of radix trichosanthis and 1 part of dried ginger.

Further, there is provided a method of preparing the capsule, comprising the steps of:

taking 5-15 parts of high-quality photinia serrulata, 5-15 parts of radix stephaniae sinensis, 3 parts of radix trichosanthis and 1 part of dried ginger according to parts by weight, respectively putting the raw materials into a crusher for crushing, crushing and sieving for later use;

the Chinese medicinal capsule for treating dysmenorrhea, toothache, gastralgia, arthralgia, labor pain, operation pain, cancer pain, etc. is prepared by mixing pulverized caulis et folium piperis, radix Chloranthi Serrati, radix Trichosanthis Cucumeroidis, and rhizoma Zingiberis in a mixer, and packaging into capsule shell.

Typical case 1:

liu certain 45 years old, male and gout can not enter normal sleep state, and the pain-relieving medicines on the market are not better. The traditional Chinese medicine capsule is recommended to be used by a hospital doctor for 1-2 granules, the pain relieving effect is achieved after 50 minutes, the pain is greatly reduced after the capsule is continuously taken for 5-6 hours, and the capsule is not taken after sleep improvement, so that the pain relieving effect of the traditional Chinese medicine capsule is realized, and the pain of a patient is fundamentally relieved.

Typical case 2:

a woman in the age of 56 with Luo-Zhi-Shi cannot go into normal sleep due to headache caused by cervical spondylosis. The traditional Chinese medicine capsule is recommended to be used by a hospital doctor, the pain relieving effect is achieved after 150 minutes, and after the traditional Chinese medicine capsule is continuously taken for 13 hours, the traditional Chinese medicine capsule is improved in sleep and is not taken again, so that the headache treating capsule can treat headache and fundamentally relieve pain of patients.

Typical case 3:

a male with age 49 years old has toothache manifested as red and swollen gums and pain stimulated by cold and heat. The traditional Chinese medicine capsule is recommended to be used by a hospital doctor for 1-2 granules, the effect is obvious after 10 minutes, and the traditional Chinese medicine capsule is not taken for the second time for improving sleep, so that the toothache can be treated, and the pain of a patient can be relieved.

Typical case 4:

li Shi 28 years old, female, antenatal labor pain. The traditional Chinese medicine capsule is recommended to be used by doctors in hospitals for 2-3 granules, and after 50 minutes, the effect is obvious, and the traditional Chinese medicine capsule is not taken for two times, so that the traditional Chinese medicine capsule can treat childbirth pain and fundamentally relieve pain of patients.

Typical case 5:

liangzhi 58 years old, female, lumbago. The traditional Chinese medicine capsule is recommended to be used by a hospital doctor for 1-2 granules, and after 45 minutes, the effect is remarkable, and the traditional Chinese medicine capsule is not taken for the second time, so that the traditional Chinese medicine capsule can treat arthralgia and fundamentally relieve pain of patients.

Capsules of the Chinese medicinal composition clinically used prove that the composition has definite curative effect, safety and reliability. The product is consistently approved by patients with the advantages of quick response and small dosage of pure traditional Chinese medicines, and has good response effect on patients in clinical use.

Variations and modifications to the above-described embodiments may occur to those skilled in the art, which fall within the scope and spirit of the above description. Therefore, the present invention is not limited to the specific embodiments disclosed and described above, and some modifications and variations of the present invention should fall within the scope of the claims of the present invention. Furthermore, although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

Claims

1. A traditional Chinese medicine composition for treating pain is characterized by being prepared from the following raw material medicines in parts by weight of photinia serrulata stem (Chinese photinia herb)Piper wallichii (Miq.) hand-Mazz 5-15 weight parts, and Wako root (Silene viscidulaFranch) 5-15 parts by weight of radix Trichosanthis Cucumeroidis (Trichosanthes cucumeroides Maxim.)1-10 weight parts, dried ginger (rhizoma Zingiberis recens)Zingiber officinaleRosc.)1-10 parts by weight.

2. The traditional Chinese medicine composition for treating pain according to claim 1, which is prepared from the following raw material medicines in parts by weight: 5 parts of photinia serrulata, 5 parts of radix stephaniae tetrandrae, 3 parts of radix trichosanthis and 1 part of dried ginger.

3. The method for preparing a Chinese medicinal composition for treating pain according to claim 1 or 2, which comprises the steps of: weighing the raw materials, adding 70-90 wt.% ethanol 8-15 times the volume of the weighed raw materials, reflux-extracting for 1-3 times (1-3 h each time), filtering the extractive solution, and mixing the filtrates for use; decocting the residue in water for 1-3 times, extracting for 1-3 times, each for 1-3 hr, mixing the two filtrates, concentrating under reduced pressure, adding ethanol to 60-80 wt.%, standing, filtering, mixing the filtrate with the ethanol extractive solution, and concentrating under reduced pressure.

4. The preparation method of the traditional Chinese medicine composition for treating pain according to claim 3, wherein 85wt.% of ethanol is added into the weighed raw materials for reflux extraction for 1 time, the extraction time is 2 hours, and the raw materials are filtered for standby; extracting the residue with water twice, the first time extracting with 8 times of water for 2 hr, the second time extracting with 6 times of water for 1 hr, filtering, mixing the filtrates, concentrating under reduced pressure, adding ethanol to 70wt.%, standing, filtering, mixing the filtrate with the ethanol extractive solution, and concentrating under reduced pressure until each ml of ethanol extractive solution is equal to 1.15-1.21g crude drug.

5. Use of a Chinese medicinal composition according to claim 1 or 2 for the manufacture of a medicament for the treatment of pain.