CN107349310B

CN107349310B - Traditional Chinese medicine composition for treating cancer pain and application thereof

Info

Publication number: CN107349310B
Application number: CN201710350913.XA
Authority: CN
Inventors: 潘华峰; 赵自明; 史亚飞; 李思怡; 曾晓会; 严艳; 刘友章; 蔡甜甜; 陈晓东; 林钟宇; 赵金媛
Original assignee: Guangzhou University of Chinese Medicine
Current assignee: Guangzhou University of Chinese Medicine
Priority date: 2017-05-17
Filing date: 2017-05-17
Publication date: 2021-01-15
Anticipated expiration: 2037-05-17
Also published as: CN107349310A

Abstract

The invention relates to a traditional Chinese medicine composition for treating cancer pain and application thereof. The active ingredients of the traditional Chinese medicine composition comprise the following components in parts by weight: 2-15 parts of rhizoma cyperi, 2-15 parts of pseudo-ginseng, 2-15 parts of ligusticum wallichii, 2-15 parts of angelica sinensis, 1-5 parts of dragon's blood, 30-45 parts of flos caryophyllata, 10-25 parts of fructus evodiae and 2-8 parts of catechu. The traditional Chinese medicine composition has the effects of warming and nourishing spleen and stomach, detoxifying and removing blood stasis, resisting cancer and relieving pain, can be used for treating patients with gastric precancerous lesions caused by coexistence of deficiency and excess and mixed cold and heat, has the effects of improving symptoms (gastrectasia, stomachache and dyspepsia) of the patients, has the effect of resisting pain caused by tumor-pressing nerves on ASG gastric cancer transplantation tumor nude mice, and has a remarkable analgesic effect on pain mice.

Description

Traditional Chinese medicine composition for treating cancer pain and application thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a traditional Chinese medicine composition for treating cancer pain and application thereof.

Background

Cancer pain is one of the common symptoms of cancer patients, with about 40% to 70% of patients with tumors developing cancer pain of varying degrees, and patients with intermediate and advanced tumors having pain incidence rates as high as 90%, of which nearly 40% are severe pain. The cancer pain not only affects the daily life, interpersonal communication and life quality of the patient, but also causes a plurality of adverse psychological states of depression, anxiety, despair and the like of the patient, and even causes the patient to stop treatment, suicide and the like in serious cases. Accurately evaluating the pain degree of a tumor patient and effectively controlling the pain in time become one of the key contents of the primary clinical care.

At present, cancer pain is treated by WHO three-step normalized treatment, the curative effect is obvious, analgesics mainly including opium can relieve more than or equal to 95 percent of pain patients, but adverse reactions are more after long-term administration, such as peptic ulcer bleeding, liver and kidney function damage, nausea, vomiting, sleepiness, respiratory depression, addiction and dependence of opium caused by non-steroidal anti-inflammatory drugs. Therefore, the traditional Chinese medicine composition can improve the analgesic effect, simultaneously reduce the adverse reaction of the medicine, and improve the life quality of cancer pain patients, and is an urgent problem to be solved in cancer pain treatment.

On the basis of the classic theory of traditional Chinese medicine, the modern traditional Chinese medicine considers that the pathogenesis of cancer pain can be summarized into 'obstruction leading to pain' and 'obstruction leading to pain', namely the cancer pain is caused by phlegm turbidity and blood stasis, coagulation and blockage of viscera and meridians, unsmooth qi movement, blood circulation blockage and obstruction leading to pain; meanwhile, qi and blood cannot be normally distributed around the body, so that the zang-fu organs and meridians are not nourished and not nourished, causing pain. Many studies at home and abroad for many years show that the traditional Chinese medicine methods of oral administration and external treatment, acupoint application, acupuncture and moxibustion and the like have the advantages of reliable curative effect, less side effect, safe use, no addiction, withdrawal syndrome and the like, and the combined use of western medicines can relieve the toxic and side effects of analgesic medicines, improve the analgesic curative effect and improve the life quality of patients.

The acupoint application method is characterized in that a traditional Chinese medicine package with strong fragrance, strong smell and strong penetrability is preheated and then placed on a diseased part of a body or a certain specific position (acupoint) of the body, or acts on an affected part nearby, or penetrates into skin and goes deep into viscera through conduction of meridians and collaterals, so that the purposes of warming and activating meridians, regulating qi and blood, clearing damp and dispelling cold, expelling toxin and attacking toxin, and eliminating stagnation and relieving pain are achieved, the effects of quick response, simplicity and safety, low price and few toxic and side effects are achieved, and the oral medicine can be prevented from being influenced by the pH value of gastrointestinal tracts, bacteria and enzymes, and the first pass metabolism and toxic and side effects are improved. Is especially suitable for patients with late stage cancer with deficiency of vital energy, poor spleen and stomach function, and oral intake incapability.

Disclosure of Invention

Based on the above, the invention provides a traditional Chinese medicine composition for treating cancer pain.

The specific technical scheme is as follows:

the active ingredients of the traditional Chinese medicine composition for treating cancer pain comprise the following components in parts by weight: 2-15 parts of rhizoma cyperi, 2-15 parts of pseudo-ginseng, 2-15 parts of ligusticum wallichii, 2-15 parts of angelica sinensis, 1-5 parts of dragon's blood, 30-45 parts of flos caryophyllata, 10-25 parts of fructus evodiae and 2-8 parts of catechu.

In some embodiments, the active ingredients of the traditional Chinese medicine composition for treating cancer pain comprise the following components in parts by weight: 3-5 parts of rhizoma cyperi, 3-5 parts of pseudo-ginseng, 3-5 parts of ligusticum wallichii, 3-5 parts of angelica sinensis, 1.5-2.5 parts of dragon's blood, 38-42 parts of flos caryophyllata, 13-17 parts of fructus evodiae and 3-5 parts of catechu.

In some embodiments, the active ingredients of the traditional Chinese medicine composition for treating cancer pain comprise the following components in parts by weight: 4 parts of rhizoma cyperi, 4 parts of pseudo-ginseng, 4 parts of ligusticum wallichii, 4 parts of angelica sinensis, 2 parts of dragon's blood, 40 parts of flos caryophyllata, 15 parts of fructus evodiae and 4 parts of catechu.

In some embodiments, the traditional Chinese medicine composition for treating cancer pain further comprises 6-18 parts of crude salt.

In some embodiments, the traditional Chinese medicine composition for treating cancer pain further comprises 9-13 parts of crude salt.

In some embodiments, the traditional Chinese medicine composition for treating cancer pain further comprises 11 parts of crude salt.

The invention also provides application of the traditional Chinese medicine composition.

The specific technical scheme is as follows:

the application of the traditional Chinese medicine composition in preparing medicines for treating cancer pain.

The invention also provides a medicine for treating cancer pain.

The specific technical scheme is as follows:

a medicine for treating cancer pain is prepared from the traditional Chinese medicine composition and auxiliary materials acceptable in the medicine.

In some of these embodiments, the medicament is in the form of a hot compress.

The invention also provides a fomenting bag for treating cancer pain.

The specific technical scheme is as follows:

a fomenting bag for treating cancer pain, which comprises the traditional Chinese medicine composition.

The invention also provides a preparation method of the fomenting bag for treating cancer pain.

The specific technical scheme is as follows:

a preparation method of a fomenting bag for treating cancer pain comprises the following steps:

(1) crushing the components in the traditional Chinese medicine composition into coarse powder, and mixing to obtain medicine powder;

(2) and filling the medicine powder into a first cloth bag, and sealing to obtain the traditional Chinese medicine bag.

In some embodiments, the method for preparing the fomenting bag for treating cancer pain further comprises the following steps: (3) packaging the sealed Chinese medicinal bag in a constant temperature bag.

In some of these embodiments, the method of making the thermostatic bag comprises the steps of:

manufacturing a second cloth bag with a bag opening, and arranging a sealing piece for opening or closing the second cloth bag at the bag opening;

embedding the double-layer insulated metal heating wire into the polyvinyl chloride film layer to obtain an insulated metal heating layer, and arranging a charging interface at the end part of the insulated metal heating layer;

and trimming and sewing the insulating metal heating layer and the inner surface of the second cloth bag, sealing the insulating metal heating layer and the inner surface of the second cloth bag by using epoxy resin, and arranging an opening which is adaptive to the charging interface on the second cloth bag to obtain the insulating metal heating cloth bag. The constant temperature bag can be charged to enable the metal heating wire to generate heat, so that the traditional Chinese medicine bag in the constant temperature bag is heated, and the temperature can be adjusted.

In some of these embodiments, the first drape has dimensions of (19-21cm) by (24-26cm) and the second drape has dimensions of (21-23cm) by (26-28 cm).

The traditional Chinese medicine composition for treating cancer pain and the application thereof have the following advantages and beneficial effects:

the inventor of the invention discovers through a large amount of creative experimental researches that the composition obtained by combining the rhizoma cyperi, the pseudo-ginseng, the ligusticum wallichii, the angelica sinensis, the dragon's blood, the flos caryophyllata, the fructus evodiae and the catechu according to a certain proportion has a remarkable analgesic effect and a remarkable effect of treating cancer pain. Crude salt is further selected to be mixed with the medicines, and when the medicine is externally applied, the medicine can help the medicine property to penetrate into the skin. The traditional Chinese medicine composition adopts cyperus rotundus and pseudo-ginseng as the medicines for promoting blood circulation and relieving pain as the monarch medicines; the blood-nourishing and blood-activating medicaments of ligusticum wallichii, angelica and dragon's blood are used as ministerial medicaments, the analgesic medicaments of clove and catechu which have anticancer effect and the anti-gastric ulcer medicament of evodia rutaecarpa are used as adjuvant medicaments, crude salt is used for assisting the medicament properties to penetrate into the skin, and the medicaments are combined to achieve the synergistic effect and the obvious analgesic effect.

The traditional Chinese medicine composition has the effects of warming and nourishing spleen and stomach, detoxifying and removing blood stasis, resisting cancer and relieving pain, can be used for treating patients with stomach cancer pain caused by deficiency and excess coexistence and mixed cold and heat, has the effects of improving symptoms (gastrectasia, stomach pain and food stagnation) of the patients, has the effect of resisting pain caused by tumor-pressing nerves on ASG (ASG gastric carcinoma) stomach cancer transplantation tumor nude mice, and has a remarkable analgesic effect on pain mice.

The traditional Chinese medicine composition is prepared into a patch or a fomenting bag for use, has better effect, and sodium ions in salt and the drug properties of other medicines in the formula enter the skin together after being heated, so that local blood vessels are better expanded, the medicines are helped to permeate into the body, and the effects of detoxifying, removing blood stasis and relieving pain are achieved.

The traditional Chinese medicine composition disclosed by the invention is prepared into a fomenting bag form for use, so that the better analgesic effect is achieved. Compared with an external treatment method by applying traditional Chinese medicines, the fomenting bag disclosed by the invention can be used for treating, and the occurrence of contact rash reaction can be avoided. And can improve the defects that the traditional fomenting bag heated by a microwave oven is inconvenient to use, burns the skin due to overhigh temperature or can not release the drug effect due to overlow temperature. The fomenting bag can improve the analgesic effect on tumor patients, has lasting drug effect, is safe and portable, provides a new treatment means without toxic and side effects for cancer patients, and has important application value and development prospect.

Drawings

FIG. 1 is a diagram showing the construction of the fomenting bag in example 1; wherein, 1 is a second cloth bag, 2 is a first cloth bag, 3 is an insulated metal heating layer, 4 is a charging interface, 5 is medicine powder, 6 is a temperature control device, 7 is a temperature button, 8 is a time button, 9 is a charging connector, 10 is a conductive wire, and 11 is a charging plug;

FIG. 2 is a schematic view of the layered structure of the fomenting bag in example 1; wherein 1 is a second cloth bag, 2 is a traditional Chinese medicine bag, 3 is an insulating metal heating layer, and 12 is a cotton layer.

Fig. 3 is a schematic diagram of the usage of the fomenting bag in embodiment 1.

Detailed Description

The present invention will be described in further detail with reference to the following embodiments and accompanying drawings.

Example 1

The embodiment provides a fomenting bag for treating cancer pain (as shown in fig. 1 and fig. 2), and the preparation method comprises the following steps:

(1) 4 parts of rhizoma cyperi, 4 parts of pseudo-ginseng, 4 parts of ligusticum wallichii, 4 parts of angelica sinensis, 2 parts of dragon's blood, 40 parts of flos caryophyllata, 15 parts of fructus evodiae and 4 parts of catechu are ground into 2-4mm coarse powder and mixed with 11 parts of crude salt to obtain medicine powder.

(2) And (3) filling the medicine powder into a single-layer pure cotton cloth bag (marked as a first cloth bag) with the thickness of 20cm × 25cm, and sealing to obtain the traditional Chinese medicine bag.

(3) Packaging the sealed Chinese medicinal bag into outer constant temperature bag.

The preparation method of the outer layer constant temperature bag comprises the following steps:

making a pure cotton cloth bag (marked as a second cloth bag) of 22cm by 27 cm; the second cloth bag is provided with a bag opening and a transverse zipper for opening or closing the second cloth bag, so that the traditional Chinese medicine bag can be conveniently put in and taken out.

Embedding the double-layer insulated metal heating wire into a polyvinyl chloride (PVC) film layer to obtain an insulated metal heating layer; one end of the insulating metal heating layer is provided with a charging interface. The double-layer insulated metal heating wire can be connected with a power supply device through the charging interface and is charged; and a temperature control device is also arranged between the power supply device and the charging interface, so that the temperature and the time can be conveniently adjusted.

And trimming and sewing the insulating metal heating layer and the inner surface of the second cloth bag, sealing the insulating metal heating layer and the inner surface of the second cloth bag by using epoxy resin, and arranging an opening corresponding to the charging interface on the second cloth bag to obtain the insulating metal heating layer.

The outer constant temperature bag can be charged to enable the metal heating wire to generate heat, so that the traditional Chinese medicine bag in the constant temperature bag is heated, and the temperature can be adjusted.

Avoid scalding the hand when using, set up the cotton layer between second bale of cloth and first bale of cloth, perhaps the internal surface of second bale of cloth and insulating metal generate heat between the layer, this cotton layer is used for generating heat and alleviates the temperature and keep medicine penetrability when the layer high temperature.

In order to fix the fomenting bag in use, a waterproof canvas belt with adjustable length can be arranged on the outer surface of the outer layer constant temperature bag corresponding to the inner surface provided with the insulating metal heating layer.

The application method of the fomenting bag comprises the following steps: charging for 5-10 minutes, and switching off when the temperature reaches 60-70 deg.C (or in charging state), and adjusting the temperature to comfortable level; the foment bag is placed on the acupoint related to the cancer pain of the patient. The Chinese medicine bag 1 can be used for 3-5 days, and the Chinese medicine bag needs to be replaced immediately after the medicine smell disappears; the treatment is performed 1-3 times per day for about 30 min. Can be adjusted according to actual conditions. As shown in fig. 3.

Example 2 analgesic Effect of Weijianning on acetic acid writhing in mice

1 materials and methods

1.1, 40 NIH mice with the weight of 18-20 g and half female and half male provided by the medical experimental animal center of Guangdong province are used as the animals, the production license number of the experimental animal is SCXK (Guangdong) 2013-; animal experiment environment: the facility use license number is SYXK (Guangdong) 2010-0059 in SPF animal laboratory of traditional Chinese medicine research institute of Guangdong province.

1.2 drugs and reagents

The traditional Chinese medicine composition for treating cancer pain (recorded as Weijianning in the invention) comprises the following components in parts by weight: 4 parts of rhizoma cyperi, 4 parts of pseudo-ginseng, 4 parts of ligusticum wallichii, 4 parts of angelica sinensis, 2 parts of dragon's blood, 40 parts of flos caryophyllata, 15 parts of fructus evodiae, 4 parts of catechu and 11 parts of crude salt. The Chinese medicinal materials are provided by research institute of Chinese medicinal engineering technology in Guangdong province, the analysis room is used for identifying Chinese medicinal materials, the preparation room is prepared into plaster, the Chinese medicinal materials are pulverized, 5% carbomer is added, and distilled water is used for adjusting the dosage to high and low dosage; storing at-4 deg.C for use.

1.3 Main apparatus BS224S electronic balance (1/ten thousand), product of SARTORIUS, Germany; YLS-6B Intelligent hot plate instrument, Shanghai precision instruments and meters products.

2 Experimental methods and results

40 mice, randomly divided into 4 groups of 10 mice each, were designated as the control group: and (5) coating distilled water. ② aspirin group: aspirin 600mg/kg is administrated by intragastric administration, and the administration volume is 20 ml/kg. ③ stomach-invigorating and calming high-dose group. And fourthly, the stomach-invigorating low-dose group. The administration was performed 1 time per day for 5 consecutive days, and 0.2ml/10g of 0.6% acetic acid solution was intraperitoneally injected on day 5 while counting with a stopwatch. The number of writhing reactions (abdominal contractions, invaginations, body twists, extending hind limbs) occurred within 15min was recorded. The percent (%) of drug analgesia was (number of writhing in control group-number of writhing in administration group)/number of writhing in control group × 100%. The results are shown in Table 1.

The results show that the high and low dose groups of the plaster of the traditional Chinese medicine composition can obviously reduce the times of writhing of mice, and the plaster of the traditional Chinese medicine composition has obvious analgesic effect.

TABLE 1 analgesic effect of Weijianning on writhing model of mice

P <0.05, P <0.01, compared to placebo

Example 3 analgesic Effect of Weijianing on liver cancer mice

1 method of experiment

Diethylnitrosamine-induced liver cancer model: mice (No. 44007200025543) were randomly divided into 4 groups (blank control group, model control group, 2 administration groups). The mice are fed with 30 mu g/mL of drinking water every day^-1The solution of DEN, a blank control group of mice, was fed with sterile distilled water and used for analgesic experiments after 23 weeks of continuous molding.

Removing hair 1 x 1cm from abdomen of model animal²Putting the mouse in a (55 +/-0.5) DEG C hot plate instrument, taking the licked foot as an index of pain response, recording the time required from putting the mouse in the hot plate instrument to licking the foot at the mouth of the mouse, measuring for 1 time on the 2 nd day, taking the average value of 2 continuous days as a basic pain threshold value before administration, predicting that the mouse is qualified when the pain threshold value is less than 5s and less than 30s, randomly dividing 40 mice with qualified pain thresholds into 4 groups, and dividing 10 mice in each group into a blank control group: coating distilled water; model comparison group: coating distilled water; ③ stomach-invigorating high-dose group; and fourthly, the stomach-invigorating low-dose group. The administration is carried out 1 time per day for 3 days, and the pain threshold of 0.5h, 1h and 1.5h after the administration of the mice is respectively determined on the 3 rd day and is statistically analyzed.

2 results of the experiment

The results shown in table 2 show that the high and low dose groups of the traditional Chinese medicine composition can obviously improve the pain threshold of cancerous mice, and have obvious analgesic effect.

TABLE 2 analgesic effects of Weijianing on liver cancer mice: (

n＝10)

P compared to blank control group<0.05，**P<0.01; in comparison with the model set, the model set is compared,^#P<0.05，^##P<0.01。

example 4 analgesic Effect of Weijianing on ASG gastric cancer transplantable tumor nude mouse model

1 method of experiment

40 nude mice were randomly divided into 4 groups (sham operation control group, transplant tumor control group, high dose group of Weijianning, low dose group of Weijianning), and 10 mice were each group. In addition to the sham-operated control group, the other 3 groups injected 10. mu.L of ASG-containing gastric cancer cells 2X 10 into the left femoral bone marrow cavity of the nude mice⁶PBS solution, sham operation control group only sham operation without any solution injection into the bone marrow cavity. After the molding is finished, the shaving area of the abdomen of the animal is 2 x 2cm, medicines are coated according to different doses, and distilled water is coated on a sham operation control group and a transplantation tumor control group.

Observation of spontaneous pain behaviors: before and 15 days after inoculation, the nude mice are placed in a large observation box with a flat bottom surface, and after the nude mice are adapted for 5min, the left hind limb of the mice is observed to lift feet. The total 4min of observation was followed and the time for lifting the feet of the mice was recorded (excluding lifting the feet during walking and grooming).

Mechanical touch induced pain determination: and (3) placing a transparent organic glass box with the length of 26cm multiplied by 14cm multiplied by 26cm on a wire net rack which is about 22cm higher than the experiment table before and 15 days after inoculation, placing a mouse to be tested in the box for adaptation for 15min, and vertically stimulating the middle part of the sole of the left hind limb of the mouse by using VonFley fiber yarns to enable the mouse to be slightly S-shaped, wherein the duration time is not more than 4S, and the foot lifting or licking behavior is regarded as positive reaction, otherwise, the reaction is negative reaction. The stimulation strength is started from 1.3g, when the stimulation of the strength can not cause positive reaction, the stimulation of the adjacent larger strength is given, if the positive reaction occurs, the stimulation of the adjacent smaller strength is given, and the steps are continuously carried out, wherein each time interval is 15 s. Then, the 50% withdrawal threshold was calculated using the method reported by Dixon.

2 results of the experiment

The results show that the high and low dose groups of the plaster of the traditional Chinese medicine composition can obviously reduce the spontaneous foot lifting time of a transplanted tumor nude mouse model and improve the foot contraction threshold by 50 percent, and the plaster of the traditional Chinese medicine composition can obviously resist the pain caused by tumor-pressed nerves.

TABLE 3 analgesic Effect of Weijianing on transplanted tumor nude mouse model: (

n＝10)

P <0.05, P <0.01, compared to the transplanted tumor control group

Example 5 clinical study of Weijianing to prevent cancer pain

1 object and method

1.1 the subjects selected from 2014 to 2016 for 6 months, 62 cases of abdominal malignant tumor patients with moderate and severe cancer pain such as gastric cancer, small intestinal cancer, large intestinal cancer, pancreatic cancer, liver cancer and the like in different periods in the first and second subsidiary hospitals of Guangzhou Chinese medicinal university and the second Chinese medicinal hospital of Guangdong province were randomly divided into 31 cases each by adopting a random number table-remainder method. Wherein the treatment groups comprise 17 men and 14 women, age 35-75 years, cancer pain course 0.5-6 (2.5 +/-1.8) months, 10 stomach cancer, 1 small intestine cancer, 10 large intestine cancer, 2 pancreatic cancer and 8 liver cancer; the control groups include 15 men and 16 women, age 36-73 years, cancer pain course 1-6 (2.4 + -1.6) months, 12 cases of gastric cancer, 2 cases of small intestinal cancer, 7 cases of large intestinal cancer, 1 case of pancreatic cancer, and 9 cases of liver cancer. The sex ratio, average age, cancer pain course and disease condition (NRS score before treatment) of the two groups of patients are compared without significant difference (P is more than 0.05), so the two groups of patients have comparability.

1.2 inclusion and rejection criteria

1.2.1 bringing the standard into the first step, diagnosing the lung cancer, the liver cancer, the stomach cancer, the breast cancer, the colon cancer and the pancreatic cancer in middle and late stages (meeting the UICC cancer diagnosis standard) by pathology, cytology and the like, and accompanying with moderate and severe pain (NRS score is more than or equal to 4 points), using a third-step medicine according to a cancer three-step pain relieving scheme, ensuring the pain part and eliminating the interference of non-cancerous pain factors; ② the age is 30-75 years old, male and female are not limited; thirdly, the syndrome differentiation of the traditional Chinese medicine belongs to the type of toxic stasis and collateral obstruction; fourthly, the voice expression ability is normal without intelligence and mental disorder, the self-pain and the general condition can be judged, and the pain, the treatment and the inspection can be cooperatively evaluated; no history of drug abuse; sixthly, patients with no serious dysfunction, no urgent and critical diseases and possibly needing rescue and operation treatment are treated; seventhly, the analgesic or sedative is not used for the first 12 hours after the group is added; eighthly, the epidermis of the abdomen is not damaged, infected and ulcerated; ninthly, understanding and agreeing to receive the treatment, and signing an informed consent.

1.2.2 rejection criteria (I) is not in accordance with inclusion criteria, and other patients with malignant tumors or the abdominal tumors are about to die at the end of diagnosis or have survival time less than 3 months; ② women of age <24 years old or >85 years old, pregnant women or women in gestation period and lactation period; ③ those who have history of drug abuse or addiction; fourthly, allergic constitution, which is allergic to certain medicines in the prescription or patients with skin allergic diseases; extensive pain or non-cancerous pain factors; sixthly, the pain can be obviously relieved by taking the measures of radiotherapy, chemotherapy and the like; seventhly, patients with serious primary cardiovascular diseases and serious liver and kidney function abnormality, or patients with primary heart, brain, liver, kidney and hematopoietic system diseases or serious tumor complications; eighty patients with mental disease; radiotherapy or nerve blocking treatment is applied to the affected part or pain part of the tumor within 1 month before the start of the observation period, or other clinical trials are being performed.

1.2.3 case shedding standard-misdiagnosis is for abdominal tumor; secondly, the medicine can not be taken on time without a prescribed method, the compliance is poor or follow-up visit can not be adhered to, patients can not finish the treatment of the cost item, and the data is incomplete; thirdly, people who naturally fall off and are lost visitors during observation; and thirdly, the illness state of the patient changes suddenly, which affects and interferes with the researchers.

1.2.4 test stopping standards, namely, poor compliance of a subject, serious adverse reaction and complication, and the subject is not suitable to continue to accept the test; ② the severe skin allergy of the patient appears in the observation process.

1.3 grouping and treatment

The selected cases were randomly divided into two groups and the attending physician given the appropriate intervention daily.

1.3.1 the control group was dosed with 100mg (starting dose) tramadol hydrochloride sustained release tablets (0.1 g/tablet, national drug standard J20130072, Beijing Mengdi pharmaceuticals Ltd.) swallowed (not chewed) at 12h intervals. If there is no pain relief, the drug dose is adjusted after 2 days, increasing by 0.1g each time, with the maximum dose being 0.4g each time. Until pain was relieved, observations were continued for 7 days. For patients with sudden pain, intramuscular injection of 0.1g of Buguochou injection; the dosage of the tramadol hydrochloride sustained release tablet is increased by 25 to 50 percent when the patient continuously breaks out for more than 2 days and the pain times per day are more than 3 times.

1.3.2 the treatment group is combined with the acupoint application treatment of the fomenting bag prepared in the embodiment 1 on the basis of the treatment of the control group, the fomenting bag is charged for 5-10min and heated, the power is cut off when the temperature reaches 60-70 ℃, and the fomenting bag is placed on the acupoints (including Shenque acupoint, Ashi acupoint, Tianshu, Zhongwan, epigastrium, moisture, Shenque, Shangqu, Qihai, Guanyuan, Tianshu and the like) related to the cancer pain of the patient after the temperature is adjusted to be comfortable. The Chinese medicinal bag 1 can be used for 3 days, and can be used for treating 1-3 times per day for 30 min.

The treatment course is 2 weeks, and the curative effect and adverse reaction are dynamically observed during the treatment period and after the treatment is finished.

1.4 Observation of therapeutic Effect

1.4.1 NRS score patients were recorded daily for pain level, time to onset and end of pain, and clinical symptoms and Karschner scores were performed.

1.4.2 clinical efficacy criteria for pain can be classified according to pain relief: (ii) Complete Remission (CR): no pain appears after treatment, the reduction of NRS method is more than or equal to 8 points; secondly, the Partial Relieving (PR) pain degree is obviously relieved compared with that before administration, the sleep quality is basically not interfered by pain, the normal daily life can be realized, and the NRS method is reduced by 5-7 minutes; mild Relief (MR): the pain degree is relieved compared with that before administration, but obvious pain is still felt, the sleep quality is interfered, and the NRS method is reduced by 3-4 minutes; (iv) Null (NR): compared with the pain before treatment, the pain is not relieved at all, and the NRS method is less than or equal to 2 points. Total effective rate (%) (complete remission + significant remission + mild remission) ÷ total number of cases × 100%, and significant effective rate (%) (complete remission + significant remission) ÷ total number of cases × 100%.

1.4.3 physical performance status according to 1948 version performance status (Karnofsky, KPS scoring standard). The karnozaky score is a composite scoring criterion for the physical performance status of tumor patients. The total score is 100, and 10 grades are divided: normal, no symptoms and signs, 100 points; normal activities with mild symptoms and signs, 90 points; it is barely able to perform normal activities, with some symptoms or signs, 80 points; the life can be self-care, but the normal life and work can not be maintained, and the score is 70; most of life can be self-care, but occasionally needs help of others, 60 points; people often need to take care of the food for 50 minutes; the life can not be self-managed, and special care and help are needed for 40 points; the life is serious and the person can not take care of himself, 30 points; severe disease, hospitalization and active supportive treatment, 20 points; critical, nearly dying, 10 points; death, 0 point.

1.4.4 onset and duration of analgesic onset time refers to the time from onset of pain relief from dosing, or the time from onset of dosing to onset of pain relief (NRS score pain relief of 2 points); the duration of analgesia refers to the time from onset of pain to the next dose.

1.4.5 quality of life of tumor patients according to the quality of life (QOL for short) standard of tumor patients established by 1990 in China: (1) appetite: the food intake is almost not enough, the food intake is less than 1/2 normal, the food intake is 1/2 normal, the food intake is slightly less, and the food intake is normal; (2) spirit: the medicine is poor, good and bad, good and good, and the medicine is normal and the same as before disease; (3) sleeping, namely, the people are difficult to fall asleep, poor in sleep, slightly poor in sleep and approximately normal; (4) fatigue: the fatigue is frequent, the consciousness is weak, the fatigue is frequent, the fatigue is mild, and the fatigue is absent; (5) pain: firstly, severe pain accompanied by passive body position or pain time is more than 6 months, secondly, severe pain, thirdly, moderate pain, fourthly, mild pain and fifthly, no pain; (6) family understanding and matching, namely, completely unintelligible, bad and general, and better family understanding and care and good; (7) understanding and co-ordination of colleagues (including leadership): firstly, fully understanding, unattended, bad, general, secondly, understanding by a few people and fifthly, understanding by a majority people; (8) self-recognition of cancer: disappointing, completely not matching, uneasy, reluctant matching, uneasy, general matching, uneasy, but better matching, optimistic and confident; (9) attitude towards treatment: firstly, the treatment is not hoped, secondly, the treatment is in doubt, thirdly, the curative effect is hoped to be seen, and the side effect is feared, fourthly, the curative effect is hoped to be seen, and can be matched, and fifthly, the treatment is confident and actively matched. (10) The daily life is as follows: the bed-ridden person can move, needs to be ridden for most of the time, can move, sometimes lies, can live in normal life, cannot work and works in normal life. (11) Side effects of treatment: the method has the advantages that the daily life is seriously influenced, the daily life is influenced, the daily life can not be influenced after symptomatic treatment, the daily life can not be influenced without the symptomatic treatment, and the daily life is not influenced. (12) Facial expression: the face is worried over the day, two eyes are not wonderful, spirit cannot be raised, spirit is still clear, no smile is generated, smile is frequently generated, a smile is always open, and spirit is full.

Grading the quality of life: the full life quality is divided into 60 grades, and the life quality is extremely poor: <20 min; poor: 21-30 minutes; ③ general: 31-40 min; fourthly, preferably: 41-50 minutes; good: 51 to 60 minutes.

1.4.6 observation and treatment of adverse reactions of tramadol sustained-release tablets refer to the national guide for cancer pain of adults (NCCN) in 2010 and the clinical research guidelines of new traditional Chinese medicines (2002) to observe, record and treat adverse reactions. For example, nausea, emesis, anorexia, acid regurgitation, marasmus, abdominal distention, constipation, brain metastasis, and hypercalcemia caused by gastrointestinal tract reaction, and is administered orally or intramuscularly; to eliminate the side effects of intestinal obstruction such as sweating, dry mouth, bitter taste, dysuria and constipation, patients can be advised to drink more water, eat more high-fiber food, exercise properly, etc. Palpitations, dizziness, somnolence, fatigue, insomnia and other adverse reactions are treated according to NCCN guidelines, and the severe adverse reactions are treated by patients who are not effective in symptomatic treatment, and the test is stopped and treated by other effective medicines/schemes. The time, symptoms, causes, passes, treatment measures, drug correlations, etc. of the event occurrence are recorded.

1.4.7 adverse reaction of external medicine treatment adverse reaction of external medicine is mainly local skin allergy, if rash, pruritus, blister and plaster drop, the medicine is immediately stopped, and the plaster is applied after no skin itch and rash subside; if blister or other damage appears on the skin of the local area where the drug is applied during the observation period, or other serious complications occur, the testers are not suitable to continue the test, the test is stopped, the patients are treated according to the symptoms, the cases are not included in the curative effect analysis, and only adverse reaction statistics are carried out.

1.5 statistical method Normal distribution measurement data plus minus standard deviation from mean

Representing that mean values between two groups are compared, and independent sample t/t' is adopted for testing; comparing the self reference mean value, and adopting pairing t test; within 50 cases, comparing the component ratio of small sample disorder count data with the median of grade data by frequency (f), component ratio/percentage (P) and average rank

Expressing that a Mann-Whitney nonparametric test is adopted, and a Wiliconxon pairing rank sum test is adopted for self comparison and self comparison; fisher exact probability method chi square (chi square) is adopted for the data of the four-grid table²) And (6) checking. Data statistics were performed by SPSS15.0 statistics software. α is 0.05.

2 results

2.1 comparison of NRS scores before and after treatment in two groups of patients: the patients in the treatment group had no significant difference in NRS score before treatment (Mann-Whitney U-422.500, P-0.531 >0.05) and significant improvement in NRS score after treatment (Mann-Whitney U-259.000, P-0.021 <0.05) as compared to the control group. Compared with the prior treatment, the NRS score mean value of the patients in the control group and the treatment group is obviously improved (Wilcoxon z is-4.654, -4.889, P is 0.000, and 0.000 is less than 0.01). See table 4.

Table 4 comparison of NRS scores before and after treatment in two groups of patients (f, P,

)

note: p <0.05, vs control group; the medicine is used before treatment with the dosage of P <0.01vs

2.2 clinical effect of pain: no significant difference in clinical efficacy of NRS scores was examined in patients treated after treatment compared to control group (Mann-Whitney U-326.000, P-0.033 < 0.05). The Fisher chi-square test shows that the total effective rate of the clinical curative effect of the treatment group is higher than that of the control group, and the total effective rate of the clinical curative effects of the two groups has no significant difference (P is 0.195 to 0.05). See table 5.

Table 5 comparison of clinical efficacy of NRS scores before and after treatment in two groups of patients (f, P,

n＝31)

note: p <0.05, vs control group

2.3 comparison of KPS scores before and after treatment between two groups of patients shows no significant difference (t ═ 0.691, P ═ 0.492>0.05) between KPS scores before and after treatment, significant increase (t ═ 6.175, P ═ 0.000<0.01) between KPS scores after treatment compared with KPS scores of control group, and significant increase (t ═ 4.322, P ═ 0.000<0.01) between KPS scores before and after treatment. Compared with the treatment group, the KPS score is obviously increased after the treatment of the patients in the control group and the treatment group (t is-10.008, -15.055, P is 0.000, and 0.000 is less than 0.01). See table 6.

TABLE 6 comparison of KPS scores before and after treatment in two groups of patients

: the novel medical treatment system has the advantages of P <0.01, vs control group, P <0.01 and vs before treatment

2.4 mean onset of analgesia in two groups of patients compared with the control group, the onset of analgesia in the treatment group was significantly shortened (t' ═ 3.069, P ═ 0.003<0.01), and the duration of analgesia in the treatment group was significantly prolonged (t ═ 13.883, P ═ 0.000<0.01) compared with the control group. See table 7.

TABLE 7 comparison of onset and duration of analgesic effect before treatment for two groups of patients

Note: first, P <0.01, vs. control group

2.5 pre-treatment and post-treatment quality of life (QOL) scores of two groups of patients compared with the pre-treatment QOL scores of the patients in the treatment group without significant difference compared with the control group (t ═ 0.734, P ═ 0.466>0.05), and the post-treatment QOL scores of the patients in the treatment group are significantly increased compared with the control group (t ═ 10.412, P ═ 0.000< 0.01); the difference in QOL scores between the treatment group and the treatment group was significantly longer than that of the control group (t-6.201, P0.000 < 0.01). Compared with the treatment group, the treatment group and the treatment group have significant increase of QOL score after treatment (t is-9.288, -15.734, P is 0.000, 0.000< 0.01). See table 8.

TABLE 8 comparison of QOL scores before and after treatment in two groups of patients

Note: the novel medical treatment system has the advantages of P <0.01, vs control group, P <0.01 and vs before treatment

2.6 adverse reaction observation the control group of patients mainly suffered from adverse reactions such as constipation, vomiting, dry mouth, dizziness and the like, and the adverse reaction incidence rates of the two groups of patients have no significant difference (P is 0.195 to 0.05) and have a reduction trend through fisher chi square test, and the adverse reaction incidence rate of the treatment group is smaller than that of the control group; the ratios of the two groups of adverse reactions are not significantly different (Mann-WhitneyU: 78.000, P: 0.487> 0.05). See table 9.

Table 9 observation and comparison of adverse reactions before and after treatment in two groups of patients (f, P,

n＝31)

note: p >0.05, vs control group

3 small knot

(1) The tramadol hydrochloride for the abdominal acupoint application of the fomenting bag prepared from the traditional Chinese medicine composition can obviously reduce the NRS score of cancer pain patients, and has more obvious analgesic effect compared with the tramadol hydrochloride alone;

(2) the traditional Chinese medicine fomenting bag prepared from the traditional Chinese medicine composition disclosed by the invention is applied to abdominal acupuncture points and combined with tramadol hydrochloride, so that KPS scores of cancer pain patients can be remarkably improved, and the physical ability of the cancer pain patients is improved;

(3) compared with single use of tramadol hydrochloride, the application of tramadol hydrochloride to the abdominal acupoint of the fomenting bag prepared from the traditional Chinese medicine composition can significantly increase QOL score of cancer patients, thereby improving life quality of cancer patients;

(4) the tramadol hydrochloride for the application of the abdominal acupoints of the fomenting bag prepared from the traditional Chinese medicine composition can reduce the incidence of adverse reactions caused by single use of tramadol hydrochloride.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims

1. The traditional Chinese medicine composition for treating cancer pain is characterized in that the active ingredients are prepared from the following components in parts by weight: 2-15 parts of rhizoma cyperi, 2-15 parts of pseudo-ginseng, 2-15 parts of ligusticum wallichii, 2-15 parts of angelica sinensis, 1-5 parts of dragon's blood, 30-45 parts of flos caryophyllata, 10-25 parts of fructus evodiae, 2-8 parts of catechu and 6-18 parts of crude salt.

2. The traditional Chinese medicine composition for treating cancer pain as claimed in claim 1, wherein the active ingredients are prepared from the following components in parts by weight: 3-5 parts of rhizoma cyperi, 3-5 parts of pseudo-ginseng, 3-5 parts of ligusticum wallichii, 3-5 parts of angelica sinensis, 1.5-2.5 parts of dragon's blood, 38-42 parts of flos caryophyllata, 13-17 parts of fructus evodiae, 3-5 parts of catechu and 6-18 parts of crude salt.

3. The traditional Chinese medicine composition for treating cancer pain as claimed in claim 2, wherein the active ingredients are prepared from the following components in parts by weight: 4 parts of rhizoma cyperi, 4 parts of pseudo-ginseng, 4 parts of ligusticum wallichii, 4 parts of angelica sinensis, 2 parts of dragon's blood, 40 parts of flos caryophyllata, 15 parts of fructus evodiae, 4 parts of catechu and 11 parts of crude salt.

4. Use of the Chinese medicinal composition of any one of claims 1-3 in the preparation of a medicament for treating cancer pain.

5. A medicament for treating cancer pain, which is characterized by being prepared from the traditional Chinese medicine composition of any one of claims 1 to 3 and pharmaceutically acceptable auxiliary materials.

6. The agent for treating cancer pain as claimed in claim 5, wherein the agent is in the form of hot compress.

7. A fomenting bag for treating cancer pain, which is characterized in that the fomenting bag comprises the traditional Chinese medicine composition of any one of claims 1 to 3.

8. A preparation method of a fomenting bag for treating cancer pain is characterized by comprising the following steps:

(1) crushing and mixing the components of the traditional Chinese medicine composition of any one of claims 1 to 3 to obtain medicine powder;

9. The method for preparing the fomenting bag for treating cancer pain according to claim 8, further comprising the following steps: (3) packaging the sealed Chinese medicinal bag in a constant temperature bag.

10. The method for preparing the fomenting bag for treating cancer pain according to claim 9, wherein the method for preparing the constant temperature bag comprises the following steps:

and trimming and sewing the insulating metal heating layer and the inner surface of the second cloth bag, sealing the insulating metal heating layer and the inner surface of the second cloth bag by using epoxy resin, and arranging an opening which is adaptive to the charging interface on the second cloth bag to obtain the insulating metal heating cloth bag.