CN107929617B

CN107929617B - Traditional Chinese medicine composition and pill for treating bone and joint tuberculosis and preparation method thereof

Info

Publication number: CN107929617B
Application number: CN201711367038.2A
Authority: CN
Inventors: 郭永昌; 张鑫杰; 罗丹; 刘文丽; 代威; 刘红月
Original assignee: ZHENGZHOU TRADITIONAL CHINESE HOSPITAL OF ORTHOPAEDICS
Current assignee: ZHENGZHOU TRADITIONAL CHINESE HOSPITAL OF ORTHOPAEDICS
Priority date: 2017-12-18
Filing date: 2017-12-18
Publication date: 2021-03-26
Anticipated expiration: 2037-12-18
Also published as: CN107929617A

Abstract

The invention discloses a traditional Chinese medicine composition for treating bone and joint tuberculosis, a pill and a preparation method thereof, wherein the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 340-360 parts of rhizoma bolbostemmae, 140-160 parts of ligusticum wallichii, 140-160 parts of longan seeds, 290-310 parts of rhizoma smilacis glabrae and 40-60 parts of bulbus fritillariae cirrhosae. The traditional Chinese medicine composition for treating tuberculosis of bones and joints has the effects of reducing phlegm and resolving masses, activating blood and relieving pain, warming and activating meridian, and inducing diuresis to alleviate edema, has obvious curative effect on suppurative diseases, namely tuberculosis of bones and joints, caused by cold phlegm coagulation, and is convenient to use.

Description

Traditional Chinese medicine composition and pill for treating bone and joint tuberculosis and preparation method thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicine compounds, and particularly relates to a traditional Chinese medicine composition and a traditional Chinese medicine pill for treating bone and joint tuberculosis and a preparation method thereof.

Background

Tuberculosis of bones and joints is a chronic pyogenic disease of bones and joints, has slow onset and slow pus generation, often forms abscess near the diseased joints, is easy to form fistula after ulceration, and cannot be cured for a long time. The disease belongs to the category of diseases of 'tuberculosis of bones', 'joint effusion' and the like in traditional Chinese medicine. The treatment method should warm and dredge meridians, resolve phlegm and dissipate nodulation. The pill has the functions of promoting blood circulation, dredging collaterals, reducing phlegm and resolving masses, and has better effect on suppurative diseases caused by phlegm accumulation in bones and joints, namely the syndrome of phlegm-blood stasis and intermingled tuberculosis of bones. The syndrome of intermingled phlegm and blood stasis of bone tuberculosis is represented as follows: the pain of the joints of the limbs is dull, stabbing, stiff, the pain part is fixed, the phlegm core exists, the joints are swollen, the flexion and extension are not good, the pain is aggravated when the limbs move, and the skin is purple and dark and has induration. Or the affected part is broken with thin pus, floccules are sandwiched, the mouth is not easy to be closed, the tongue is purple and dark or has ecchymosis, white and greasy fur, and the pulse is wiry and unsmooth. Because the disease has slow onset and lingering course of disease, the affected part is not easy to heal after being burst, the muscles and bones are often damaged, and the disability and even life threatening can be caused, thereby bringing great burden to patients and society.

At present, antitubercular drugs such as isoniazid, rifampicin and ethambutol are commonly used in western medicine for treating the disease, or the antitubercular drugs are used for washing joint cavities. But the antituberculosis drugs are easy to cause adverse reactions such as anaphylactic reaction, digestive system reaction, renal function damage, bone marrow suppression, nervous system reaction, endocrine dyscrasia and the like.

Disclosure of Invention

In view of the above, the present invention provides a new traditional Chinese medicine composition for treating bone and joint tuberculosis, a pill and a preparation method thereof.

One embodiment of the invention provides a traditional Chinese medicine composition for treating bone and joint tuberculosis, which comprises the following raw materials in parts by weight: 340-360 parts of rhizoma bolbostemmae, 140-160 parts of ligusticum wallichii, 140-160 parts of longan seeds, 290-310 parts of rhizoma smilacis glabrae and 40-60 parts of bulbus fritillariae cirrhosae.

In the traditional Chinese medicine composition for treating bone and joint tuberculosis, 345-355 parts of rhizoma bolbostemmae are adopted.

In the traditional Chinese medicine composition for treating bone and joint tuberculosis, 145-155 parts of ligusticum wallichii are used; 145-155 parts of longan seeds.

In the traditional Chinese medicine composition for treating bone and joint tuberculosis, 295-305 parts of glabrous greenbrier rhizome; the fritillaria cirrhosa is 45-55 parts.

In the traditional Chinese medicine composition for treating bone and joint tuberculosis, 350 parts of rhizoma bolbostemmae are taken; the ligusticum wallichii is 150 parts; 150 parts of longan seeds; 300 parts of glabrous greenbrier rhizome; the fritillaria cirrhosa is 50 parts.

Another embodiment of the invention provides a pill for treating bone and joint tuberculosis, which comprises the traditional Chinese medicine composition.

In the pill for treating bone and joint tuberculosis, 1-3 parts of starch and 0.155-0.165 part of microcrystalline cellulose are also added into each 100 parts of the traditional Chinese medicine composition.

Yet another embodiment of the present invention provides a method for preparing a pill for treating bone and joint tuberculosis, the pill comprising the above-mentioned Chinese medicinal composition; the preparation method comprises the following steps: and crushing the raw materials and uniformly mixing to obtain powder.

In the preparation method of the pill for treating bone and joint tuberculosis, 100 parts of powder, 1-3 parts of starch, 0.155-0.165 part of microcrystalline cellulose and 6-8 parts of pure water are mixed and stirred to prepare a wet pill.

In the above preparation method of the pill for treating bone and joint tuberculosis, the wet pill is dried to water content of less than 5% (weight) to obtain a plain pill, and the plain pill is coated with activated carbon and polished by talcum powder, wherein 0.45-0.55 part of activated carbon and 0.45-0.55 part of talcum powder are used per 100 parts of plain pill.

The traditional Chinese medicine composition for treating bone and joint tuberculosis selects pure natural traditional Chinese medicine raw materials, takes the rhizoma bolbostemmae as a monarch drug, takes the longan seed and the ligusticum wallichii as ministerial drugs, takes the rhizoma smilacis glabrae as an adjuvant drug and takes the fritillaria cirrhosa as a conductant drug, comprehensively utilizes the action advantages and mutual synergistic action of the traditional Chinese medicine raw materials, has the effects of reducing phlegm and resolving masses, promoting blood circulation and relieving pain, warming and activating meridians, inducing diuresis and relieving swelling, and expelling pus and promoting granulation, and has obvious curative effect on suppurative diseases, namely bone tuberculosis, caused by cold phlegm condensed in bones and joints. After being prepared into pills, the pill is more convenient to use. In addition, compared with western medicines, the traditional Chinese medicine composition for treating bone and joint tuberculosis has the advantages of low cost, safe use, no pain and no toxic or side effect.

In order to make the aforementioned and other objects, features and advantages of the invention more comprehensible, preferred embodiments accompanied with figures are described in detail below.

Detailed Description

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention.

This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, but rather should be construed as broadly as the present invention is capable of modification in various respects, all without departing from the spirit and scope of the present invention.

When an amount, concentration, or other value or parameter is expressed as a range, preferred range, or as a range of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether ranges are separately disclosed. For example, when the range "1 ~ 5" is disclosed, the ranges described should be construed to include the ranges "1 ~ 4", "1 ~ 3", "1 ~ 2 and 4 ~ 5", "1 ~3 and 5", and the like. When a range of values is described herein, unless otherwise stated, the range is intended to include the endpoints thereof and all integers and fractions within the range.

One embodiment of the invention provides a traditional Chinese medicine composition for treating bone and joint tuberculosis, which comprises the following raw materials in parts by weight:

340-360 parts of bolbostemma paniculatum, such as 342 parts, 345 parts, 347 parts, 350 parts, 352 parts, 355 parts or 358 parts and the like. The rhizoma bolbostemmae is preferably 345-355 parts, and more preferably 350 parts.

140-160 parts of ligusticum wallichii, such as 142 parts, 145 parts, 147 parts, 150 parts, 152 parts, 155 parts or 157 parts and the like. The rhizoma ligustici wallichii is preferably 145-155 parts, and more preferably 150 parts.

140-160 parts of longan seeds, such as 142 parts, 145 parts, 147 parts, 150 parts, 152 parts, 155 parts or 157 parts. The optimized longan seed is 145-155 parts; more preferably 150 parts.

290-310 parts of glabrous greenbrier rhizome, such as 292 parts, 295 parts, 297 parts, 300 parts, 302 parts, 305 parts or 308 parts. The rhizoma smilacis glabrae is preferably 295-305 parts; more preferably 300 parts.

40-60 parts of bulbus fritillariae cirrhosae such as 42 parts, 45 parts, 47 parts, 50 parts, 52 parts, 55 parts or 57 parts. The preferable proportion of the bulbus fritillariae cirrhosae is 45-55 parts; more preferably 50 parts.

The mother of the earth shellfish is slightly cold in nature and bitter in taste, has the effects of detoxifying, resolving masses and reducing swelling, and is used for treating acute mastitis, scrofula and subcutaneous nodule. The herbal supplement: for surgical phlegm-toxin. Baicaoshen: it can dispel carbuncle, remove pus, promote the circulation of qi, relieve sore, remove wind-damp, remove phlegm, apply malignant boil, heal wound. Selection of Chinese herbal medicine of Shanxi Ganning Qing (Shanxi Ganning): "mainly treat lymph node tuberculosis and bone tuberculosis". The book Ben Cao Hui Yan (treatise on materia Medica): tubei mu is also indicated for resolving stagnation, descending qi and resolving phlegm. Lung moistening and phlegm eliminating, cough relieving and asthma relieving, this is the syndrome of consumptive disease with accumulation of fire, and Bei mu specializes in the first dose. For resolving abscess, it is better to break mass, remove excessive phlegm and apply on malignant sores. While Chuan is superior in taste and Tu is inferior in taste, both are used separately. The rhizoma bolbostemmae has the effects of reducing phlegm and resolving masses, relieving swelling and healing sore, and has good treatment effects on tuberculosis of bone, induration, swelling and ulceration of sores.

Chuan Xiong is pungent and warm, enters liver, gallbladder and pericardium channels, and has the effects of activating blood and qi, dispelling wind and relieving pain. Rihuazi: treating the diseases of wind cutting, qi cutting, strain cutting, blood cutting, internal fatigue, muscle and bone strengthening, meridian regulating, old blood breaking, new blood nourishing, flesh growing, sore scabies and pus discharging and blood stasis removing. The rhizoma ligustici wallichii is a blood-qi-activating medicine and can activate blood, promote blood circulation, remove blood stasis, improve pain, heal wound and promote tissue regeneration.

Longan seeds are neutral in nature, slightly bitter and astringent in taste, and have the effects of promoting qi circulation, removing stasis, stopping bleeding and eliminating dampness. Longan seeds are mainly used for treating scrofula, traumatic hemorrhage and eczema. The "Renzai of materia Medica": for scrofula, it is indicated for swelling and pus discharge. Lingnan herbal medicine collection book: it is indicated for sores and ringworm, but also for bleeding due to incised wound. Longan seeds can promote qi circulation, reduce phlegm, dissipate stagnation, stop bleeding and heal wound. The rhizoma ligustici wallichii and the longan seeds are matched and used as ministerial drugs, and the rhizoma ligustici wallichii and the longan seeds are used together with monarch drugs to play the effects of reducing phlegm and resolving masses, and promoting blood circulation and removing obstruction in channels.

Smilax glabra is sweet and bland in flavor, neutral in nature, and enters liver and stomach meridians. Has the effects of removing toxic substances, eliminating dampness, and smoothing joint movement. Rhizoma Smilacis Glabrae can be used for treating limb spasm and arthralgia and myalgia due to syphilis and mercury poisoning; stranguria with turbid damp-heat, leukorrhagia, abscess, scrofula, scabies and tinea. Compendium of materia Medica: "Smilax glabra Linn is used for treating spasm, bone pain, malignant sore, carbuncle and swelling". The book on the incised usage of drug property: glabrous greenbrier rhizome, rhizoma Smilacis Glabrae has the effects of excreting dampness and heat and removing toxicity. Entry into medicine: "Smilax glabra" is good at treating red bayberry carbuncle and abscess and hourglass caused by long-standing diseases, and can recover toxicity to dispel wind and tonify deficiency in patients who take mercurous chloride by mistake, have damaged limbs and have pain in bones and muscles. It is also suitable for the old and weak to strengthen tendons and bones. The book of materia Medica: smilax glabra, rhizoma Smilacis Glabrae, with the effects of removing dampness and heat, dredging collaterals, and eliminating toxic materials due to damp-heat. Smilax glabra Linn, rhizoma Smilacis Glabrae, rhizoma Dioscoreae Septemlobae, rhizoma Smilacis Glabrae.

Chuan Bei mu is bitter and sweet in taste and slightly cold in nature, entering lung and heart meridians. Has the effects of clearing away heat, moistening lung, eliminating phlegm, relieving cough, resolving hard mass and resolving carbuncle. The book Jing: "main incised wound". The bibliography: "An Wuzang organs, benefiting marrow". The materia Medica (materia Medica essence): in Yun of Rihuazi, it is applied to malignant sores to heal the sores, so pungent herbs can dissipate nodulation, bitter herbs can reduce fire, qi and blood can be harmonized smoothly, and the sores can heal . The book of medical science: bulbus Fritillariae Cirrhosae, with its bitter and pungent properties, can reduce bitter and disperse stagnation, and has clear smell, so it is indicated for stagnant phlegm, deficient phlegm, heat phlegm and blood in phlegm, cough due to asthenia, dyspnea of chest and diaphragm, polydipsia and severe heat, this descending heat conduction, and spontaneous phlegm. It is also indicated for flaccidity of lung, pulmonary abscess, goiter, phlegm nodule, abscess, deep-rooted carbuncle and sore, all of which can dispel stagnation and dissipate nodulation, and circulate blood vessels. It is also good at regulating spleen qi and treating up-flaming of stomach fire due to its cool nature and descending of energy. Chong and forcing lung to be golden, causing phlegm cough, clearing qi and nourishing yin, and self-healing of lung. Chuan Bei mu can resolve phlegm, dissipate nodulation and heal wound, and harmonize the other herbs as guiding herbs.

The traditional Chinese medicine composition for treating bone and joint tuberculosis disclosed by the invention takes the rhizoma bolbostemmae as a monarch drug, takes the longan seed and the ligusticum wallichii as ministerial drugs, takes the rhizoma smilacis glabrae as an adjuvant drug and takes the fritillaria cirrhosa as a conductant drug, comprehensively utilizes the action advantages and mutual synergistic action of the raw materials of the traditional Chinese medicines, has the effects of reducing phlegm and resolving masses, promoting blood circulation and relieving pain, warming and activating meridians, inducing diuresis to alleviate edema, expelling pus and promoting granulation, and has a remarkable curative effect on suppurative disease, namely bone tuberculosis, caused by cold phlegm condensed in bones and joints. And is convenient to use.

Another embodiment of the invention provides a pill for treating bone and joint tuberculosis, which comprises the traditional Chinese medicine composition. 1-3 parts of starch and 0.155-0.165 part of microcrystalline cellulose are also added into every 100 parts of the traditional Chinese medicine composition; preferably, 2 parts of starch and 0.16 part of microcrystalline cellulose are also added into each 100 parts of the traditional Chinese medicine composition.

Yet another embodiment of the present invention provides a method for preparing a pill for treating bone and joint tuberculosis, the pill comprising the above-mentioned Chinese medicinal composition; the preparation method comprises the following steps: and crushing the raw materials and uniformly mixing to obtain powder. 100 parts of the powder, 1-3 parts of starch, 0.155-0.165 part of microcrystalline cellulose and 6-8 parts of pure water are mixed and stirred to prepare wet pills. The wet pellets may be dried to a moisture content of 5% by weight or less (preferably 3% or less) to obtain plain pellets, and the plain pellets are carbon-coated with activated carbon and polished with talc, wherein 0.45-55 parts of activated carbon and 0.45-0.55 part of talc are used per 100 parts of plain pellets. Preferably, 0.5 parts of activated carbon and 0.5 parts of talc are used per 100 parts of vegetarian pellet.

The traditional Chinese medicine composition and the pill thereof are safe to use and have no toxic or side effect. The pill is simple to prepare, easy to take and convenient to carry, does not need or needs few auxiliary materials during preparation, is low in cost and suitable for mass production, and therefore the dosage form is preferably the pill. Of course, other formulations such as tablets, capsules, granules and the like may be prepared as required. A specific example of the manufacture of the pill is given below.

The equipment for pulverizing the raw materials into powder can be, for example, a model TF300B two-stage pulverizer (Tianjin Chinese medicine machinery factory). The powder yield of the medicinal materials can reach 95.0 percent, and the production requirement is met. The powder mixing equipment can be, for example, GH-200 type high-efficiency three-dimensional motion mixer (Harbin pharmaceutical chemical engineering equipment Co., Ltd.), and for example, 20Kg of tuberculosis pill powder can be mixed in the mixer for 40 minutes.

Weighing the medicinal powder, starch and microcrystalline cellulose according to the above formula, placing in a trough type mixer (such as CHJ-200 trough type mixer of Gansu Tianshuihua Garden pharmaceutical technology Co., Ltd.) and stirring for 10 min, adding purified water and stirring for about 20 min to obtain soft material.

The soft material is placed in an intelligent efficient full-automatic pill making machine (for example, YUJ-17B type intelligent efficient full-automatic pill making machine of Gansu Tianshuihua pharmaceutical equipment science and technology Limited) to be subjected to bracing and pill rolling to obtain round, uniform and uniform wet pills with consistent appearance, and the diameter of the wet pills can be 4.0-4.3 mm.

Placing 27.432Kg wet pill in a microwave drying and sterilizing box (such as HWL15-1 microwave drying and sterilizing box of Gansu Tianshuihua David pharmaceutical equipment science and technology Co., Ltd.) with hot air at 50 deg.C and drying at 80 deg.C for 50-60 minutes. The water content of the dried pill is controlled below 5%.

Placing the vegetarian pill in a sugar-coating pan (such as TG-1000 sugar-coating pan of Gansu Tianshuihua pharmaceutical equipment science and technology Co., Ltd.) to coat with charcoal and pulvis Talci, and adding 500g of activated carbon and pulvis Talci to each 100Kg of vegetarian pill.

In order to facilitate understanding of the present invention, the technical solutions of the present invention will be further described below with reference to examples and specific cases.

Example 1

The traditional Chinese medicine composition for treating tuberculosis of bones and joints comprises the following components: 350 parts of rhizoma bolbostemmae, 150 parts of ligusticum wallichii, 150 parts of longan seeds, 300 parts of rhizoma smilacis glabrae and 50 parts of bulbus fritillariae cirrhosae.

The Chinese medicinal raw materials are prepared according to the specific example for preparing the pill.

Example 2

The traditional Chinese medicine composition for treating tuberculosis of bones and joints comprises the following components: 340 parts of rhizoma bolbostemmae, 140 parts of ligusticum wallichii, 140 parts of longan seeds, 290 parts of rhizoma smilacis glabrae and 40 parts of bulbus fritillariae cirrhosae.

The traditional Chinese medicine raw materials are prepared into pills according to the method.

Example 3

The traditional Chinese medicine composition for treating tuberculosis of bones and joints comprises the following components: 360 parts of rhizoma bolbostemmae, 160 parts of ligusticum wallichii, 160 parts of longan seeds, 310 parts of rhizoma smilacis glabrae and 60 parts of bulbus fritillariae cirrhosae.

Example 4

The traditional Chinese medicine composition for treating tuberculosis of bones and joints comprises the following components: 345 parts of rhizoma bolbostemmae, 145 parts of ligusticum wallichii, 145 parts of longan seeds, 295 parts of rhizoma smilacis glabrae and 45 parts of bulbus fritillariae cirrhosae.

Example 5

The traditional Chinese medicine composition for treating tuberculosis of bones and joints comprises the following components: 355 parts of rhizoma bolbostemmae, 155 parts of ligusticum wallichii, 155 parts of longan seeds, 305 parts of rhizoma smilacis glabrae and 55 parts of bulbus fritillariae cirrhosae.

Comparative example 1

Different from the embodiment 1, the dosage of the fritillaria thunbergii is 300 parts, and other components and the preparation method are the same as the embodiment 1.

Comparative example 2

Different from the embodiment 1, the dosage of the fritillaria thunbergii is 400 parts, and other components and the preparation method are the same as the embodiment 1.

Comparative example 3

Different from the embodiment 1, the using amount of the hemlock parsley is 100 parts, and other components and the preparation method are the same as the embodiment 1.

Comparative example 4

Except for the difference from example 1, the amount of longan seeds is 100, and other components and preparation method are the same as example 1.

Comparative example 5

Different from example 1, the amount of smilax glabra is 250, and other components and preparation methods are the same as example 1.

Comparative example 6

Different from the embodiment 1, the dosage of the bulbus fritillariae cirrhosae is 30, and other components and the preparation method are the same as the embodiment 1.

The effect of the pill of example 1 was verified, and 250 patients (age 40-65 years) with tuberculosis of bone and joint were randomly divided into 5 groups of 50 patients, and the pill of example 1-5 was administered to each patient for treatment according to the above-mentioned application method. The administration method comprises the following steps: the preparation is administered once 6g, three times a day, 10 days as a treatment course, and 5 treatment courses.

And (3) judging the curative effect:

and (3) curing: the signs of symptoms have substantially disappeared.

The method has the following advantages: the signs of symptoms were relieved.

And (4) invalidation: signs of symptoms were not improved prior to treatment.

After the traditional Chinese medicine granules are prepared, the statistical results are as follows:

examples	Total number of people	Cure of disease	Is effective	Invalidation	Cure rate	High efficiency
							1	50	47	2	1	94％	98％
2	50	39	5	6	78％	88％
							3	50	40	6	4	80％	92％
4	50	43	4	3	86％	94％
							5	50	44	3	3	88％	94％

As shown in the table, the traditional Chinese medicine composition has good effect after treatment, the effective rate is more than 88%, and the cure rate is more than 78%. In addition, the effects of examples 4 and 5 are excellent, and the effect of example 1 is the best, in terms of the overall cure rate and efficacy.

In addition, the inventors also treated 6 groups of patients (5 per group) individually with the pills prepared in comparative examples 1 to 6, all of which had no or poor therapeutic effect.

The following is a list of relevant animal tests performed using the protocol of the present invention.

Experiment 1 influence of Gulao pills on acetic acid-induced writhing response in mice

1 materials of the experiment

1.1 test drugs: bone tuberculosis pill (pill made according to example 1)

Orally administered three times daily, 6g each time. The test sample is prepared into a proper concentration by 0.1 percent CMC-Na at the time of clinical application.

1.2 Positive drugs: aspirin tablets, 50 mg/tablet, were manufactured by Hunan Asia Dada pharmaceuticals, Inc. In the experiment, 0.1% CMC-Na is used to prepare 0.01g/ml suspension.

1.3 animals: the weight of the Kunming mouse is 20-22g, and is provided by the center of experimental animals in Henan province.

1.4 reagent: acetic acid, produced by chemical reagent works in Luoyang.

2 method of experiment

2.1 Experimental groups

2.1.1 model control (n ═ 10): 0.1% CMC-Na, 20 ml/kg;

2.1.2 positive drug control group (n ═ 10): 0.2g/kg of aspirin;

2.1.3 pills for treating tuberculosis of bone 3.4g finished medicine/kg (17%, equivalent to 13.22 times of clinical daily dose);

2.1.4 pills for treating bone tuberculosis, 1.7 g/kg of patent medicine (8.5 percent, which is equivalent to 6.61 times of clinical daily dose);

2.1.5 pills for treating tuberculosis of bone 0.85g/kg (4.25%, equivalent to 3.31 times of clinical daily dose).

2.2 Experimental procedures

2.2.1 Each group of animals was administered by continuous gavage for 3 days 1 time per day at a rate of 20ml/kg body weight (20 ml of 0.1% CMC-Na/kg body weight in the model control group and the normal control group).

2.2.2 last 60 minutes after administration, 0.1ml/10g body weight of 0.9% acetic acid was intraperitoneally injected per mouse, and the number of writhing of the mouse within 15 minutes after the acetic acid administration was recorded.

2.3 statistical methods: comparison between groups, t-test.

3 results of the experiment

The animal writhing reaction times of the large dose group animals of the bone tuberculosis pill are less than that of the model control group, and the difference between the groups has statistical significance, which shows that the pill has a certain pain relieving effect (Table 1).

TABLE 1 influence of bone tuberculosis pill on writhing response of mice

Note: p <0.05 compared to model control group.

4 conclusion

The experiment result shows that the bone tuberculosis pill can inhibit the body writhing reaction of mice induced by acetic acid by gastric administration and has certain pain relieving effect.

Experiment 2 influence of Gulao pills on blood ecchymosis of mice

1 materials of the experiment

1.1 test drugs: the pill for bone tuberculosis (prepared according to example 1) is provided by Zhengzhou Hospital for bone injury in TCM. The functional indications are as follows: promoting blood circulation, dredging collaterals, eliminating phlegm and resolving masses; can be used for treating bone tuberculosis (bone tuberculosis). Taken orally three times a day, 10g each time. The test sample is prepared into a proper concentration by 0.1 percent CMC-Na at the time of clinical application.

1.2 Positive drugs: traumatic injury tablet, 0.25 g/tablet, is produced by Daliangliren pharmaceutical Co. Adult dosage: 4 tablets at a time, 2 times a day (2 g/day). In the experiment, 0.011g/ml suspension is prepared by 0.1 percent CMC-Na.

2 method of experiment

2.1 Experimental groups

2.1.1 model control (n ═ 10): 0.1% CMC-Na, 20 ml/kg;

2.1.2 positive drug control group (n ═ 10): traumatic injury tablet 0.22g/kg (0.011 g/ml);

2.2 Experimental procedures

2.2.1 selecting healthy mice with weight of 20-22g, wherein the thigh of the right back of each mouse is impacted by a free falling body (30cm) with weight of 100g, and then randomly dividing the mice into 5 groups, namely a positive drug (bonesetting water) control group, a model control group, and high, medium and low dose groups of tabellae, wherein each group comprises 10 mice.

2.2.2 the model control group is perfused with normal saline, and the bone tuberculosis pill group is separately perfused with the normal saline and the bone tuberculosis pill group according to the weight of 3.4, 1.7 and 0.85g/kg, and the administration is carried out 1 time per day for 5 consecutive days.

2.2.3 at 60 minutes after the last administration, the impacted area of the right rear thigh of each mouse was examined by dissection, and the degree of recovery from blood stasis was expressed by scores (1: mild blood stasis, 2: moderate blood stasis, 3: severe blood stasis, and 4: very severe blood stasis).

2.3 statistical methods: comparison between groups, t-test.

3 results of the experiment

The stagnant blood scores of the high-dose group of the tabellae ossis pills are smaller than those of the model control group, and the differences have statistical significance, which shows that the tabellae ossis pills have the function of promoting absorption of blood ecchymoses (promoting blood circulation to remove blood stasis) (Table 2).

TABLE 2 influence of Gulao pills on blood ecchymoses in mice

Note: p <0.05, compared to model control group.

4 conclusion

The experimental result shows that the bone tuberculosis pill can reduce the blood stasis value of a model mouse and has the function of promoting absorption of blood stasis spots (promoting blood circulation to remove blood stasis).

Test 3 bone tuberculosis pill acute toxicity test

The bone tuberculosis pill is given to mice for 2 times per day according to the maximum concentration and the maximum gavage capacity, and then observed for 7 days. The animals do not die, and the weight change, hair, activity, mental state, diet and the like are not abnormal. LD could not be measured due to the restriction of gavage dose₅₀Therefore, the maximum dosage of the mice after the administration of the bone tuberculosis pill through gastric perfusion is measured to be 30.4 g/Kg.d (which is equal to 118.22 times of the clinical dosage).

1 purpose: the mice were observed for the toxic reactions and deaths that occurred after administration of the bolus to the mice at maximum concentration and maximum gavage volume.

2, materials:

2.1 test drugs: pills for bone tuberculosis (prepared according to example 1). For the experiment, 0.38g/ml of suspension is prepared by 0.5 percent of sodium carboxymethyl cellulose (CMC-Na).

2.2 Experimental animals: 20 Kunming mice with the weight of 19.8 +/-1.6 g and half of male and female are provided by the experimental animal center in Henan province.

3 method

20 Kunming mice for experiment, half of the male and female, after fasting for 12h, are intragastrically administered for 2 times a day (at intervals of 8h) according to the maximum concentration of 0.38g/ml and the maximum intragastrically administrable volume (0.4ml/10 g). After administration, the animals were kept for 7 days.

4 results

After administration, mice were active normally; the hair, mental state and diet of the patient are not abnormal; the weight change is normal, the weight before administration is 19.8 plus or minus 1.6g, and the weight after one week is 25.7 plus or minus 2.4 g; mice did not die within 7 days. No LD was detected due to the dose limitation₅₀Therefore, the maximum dosage of the mice for measuring the bone tuberculosis pills is 30.4 g/Kg.d (corresponding to 118.22 times of clinical dosage).

Experiment 4 Long-term toxicity test of pills for treating bone tuberculosis

The long-term repeated administration of the bone tuberculosis pill to rats is observed, and the cumulative toxicity and the delayed toxicity reaction which are possibly generated by the bone tuberculosis pill are avoided.

1 materials of the experiment

1.1 test drugs: bone tuberculosis pill (pill made according to example 1)

In the experiment, 0.5% sodium carboxymethylcellulose (CMC-Na) is used for preparing suspensions with three concentrations of 20%, 16% and 12%.

1.2 Experimental animals: wistar rats, male and female halves, weighing 85 + -8 g, were provided by the Experimental animals center of Henan province.

1.3 kits

1) Alanine amino group converting enzyme: shanghai province, California chinensis diagnostic products.

2) Aspartate aminotransferase: shanghai province, California chinensis diagnostic products.

3) Alkaline phosphatase (alkaline phosphatase): shanghai province, California chinensis diagnostic products.

4) r-glutamyl transpeptidase: shanghai province, California chinensis diagnostic products.

5) Total protein: shanghai province, California chinensis diagnostic products.

6) Albumin: shanghai province, California chinensis diagnostic products.

7) Total cholesterol: shanghai province, California chinensis diagnostic products.

8) Triglyceride: shanghai province, California chinensis diagnostic products.

9) Blood sugar: shanghai province, California chinensis diagnostic products.

10) Urea nitrogen: shanghai province, California chinensis diagnostic products.

11) Creatinine: shanghai province, California chinensis diagnostic products.

12) Total bilirubin: shanghai province, California chinensis diagnostic products.

1.4 instruments

1) DS-671 electronic Scale, Shanghai Temple Oncki, Inc.

2) Model BS223S electronic balance, beijing sidoris instruments systems ltd.

3) MS9-5 blood cell analyzer, France.

4) Au-400 full-automatic biochemical analyzer, japan.

2 method of experiment

2.1 animal groups and administrations: the experimental Wistar rats, 80 in each half, were randomly divided into 4 groups. The feed is provided by experimental animal center in Henan province, room temperature is 23 + -2 deg.C, humidity is 50-70%, natural lighting is provided, ventilation is performed at regular time every day, group culture is performed, male and female parts are separated, 5 animals are placed in each cage, and observation is performed for 3 days before experiment. Gavage was given 1 time daily for 13 weeks.

Blank control group: CMC-Na 20 ml/kg.d;

② the high dose group of the pills for treating bone tuberculosis: 4.0g/kg.d, 15.56 times of clinical dosage;

③ bone tuberculosis pill middle dose group: 3.2g/kg.d, 12.44 times of clinical dosage;

fourthly, the low-dose group of the pills for treating bone tuberculosis: 2.4g/kg. d, 9.33 times of clinical dosage.

2.2 Observation index

1) General condition and body weight: the behavior, diet and fecal excretion of the animals were observed daily, the body weight was weighed once a week, and the dose was adjusted according to the change in body weight.

2) Blood routine determination: after 13 weeks of administration, 10 animals were taken per group, male and female, and after 12h of fasting (without water deprivation), decapitated blood was taken and subjected to routine blood determinations including red blood cell count (RBC), hemoglobin content (HGB), platelet count (PLT), white blood cell count (WBC) and white blood cell classification (LY, MO, GR). After stopping feeding for 2 weeks, 10 animals were again selected from each group, and the above-mentioned indexes were examined and measured for each half of males and females.

3) Biochemical determination of blood: after 13 weeks of administration, 10 animals were taken from each group, male and female, and after 12h of fasting (without water deprivation), decapitated blood was taken for biochemical blood determination, including alanine Aminotransferase (ALT), aspartate Aminotransferase (AST), alkaline phosphatase (ALP), Total Protein (TP), Albumin (ALB), Total Bilirubin (TBIL), total Cholesterol (CHOL), blood Glucose (GLU), myoliver (CR), and urea nitrogen (BUN). After stopping feeding for 2 weeks, 10 animals were again selected from each group, and the above-mentioned indexes were examined and measured for each half of males and females.

4) Organ index and histopathology examination: taking 10 animals each group after 13 weeks of administration, taking the animals each half female and male, after fasting for 12 hours (without water), taking blood after head breaking, carrying out systematic autopsy on the animals, and observing the anatomical positions of the organs of rats of each group by naked eyes to see whether adhesion exists, whether effusion exists in the thoracic cavity, abdominal cavity and brain, the color, shape, size, surface smoothness and the like of the organs; weighing brain, heart, liver, spleen, lung, kidney, testis and epididymis of male animal, uterus and ovary of female animal, and calculating viscera coefficient; pathological examination is performed on major organs and tissues including brain, heart, liver, spleen, lung, kidney, adrenal gland, stomach, duodenum, male testis, male epididymis, female ovary, and female uterus. After stopping feeding for 2 weeks, 10 animals were again selected from each group, and the above-mentioned indexes were examined and measured for each half of males and females.

2.3 statistical methods: results a comparison t-test between groups was performed.

3 results of the experiment

3.1 general conditions and body weight: during the administration period and after the administration is stopped, the behavior, diet and fecal excretion of animals in each dose group of the bone tuberculosis pill are not abnormal, the fur color is glossy, the animals grow well, the weight is generally increased, and compared with a blank control group, the weight increase of animals in each dose group has no significant difference (see tables 3 and 4).

TABLE 3 influence of Gulao pills on body weight of male rats

TABLE 4 influence of Gulao pills on female rat body weight

3.2 blood routine: after the administration for 13 weeks and the stopping of the administration for 2 weeks, the blood routine index of rats in each dose group of the bone tuberculosis pill is normal. Red blood cell number (RBC), hemoglobin content (HGB), platelet number (PLT), white blood cell number (WBC) and white blood cell classification (LY, MO, GR) were all within normal ranges with no significant difference compared to the blank control group (see table 5, table 6).

TABLE 5 influence of Gulao pills (13 weeks of administration) on the general indices of blood in rats

TABLE 6 influence of Gulao pills (13 weeks after administration and 2 weeks after discontinuation) on the conventional index of blood in rats

3.3 blood biochemistry: after the administration for 13 weeks and the stopping of the administration for 2 weeks, the blood biochemical indexes of rats in each dose group of the bone tuberculosis pill are normal. Alanine Aminotransferase (ALT), aspartate Aminotransferase (AST), alkaline phosphatase (ALP), Total Protein (TP), Albumin (ALB), Total Bilirubin (TBIL), total Cholesterol (CHOL), blood Glucose (GLU), myoliver (CR), and urea nitrogen (BUN) were all within normal ranges with no significant difference compared to the blank control group (see table 7, table 8).

TABLE 7 influence of Bolus for treating tuberculosis (13 weeks of administration) on biochemical index of blood of rat

TABLE 8 influence of Bolus for treating tuberculosis (13 weeks after administration and 2 weeks after discontinuation) on biochemical index of blood of rat

3.4 organ index: the organ indexes of rats in each dose group of the bone tuberculosis pill have no significant difference compared with a blank control group after 13 weeks of administration and 2 weeks of stopping administration (see tables 9 and 10).

TABLE 9 influence of Bolus for tuberculosis (13 weeks of administration) on the visceral index of rats

TABLE 10 influence of Bolus for tuberculosis (13 weeks after administration and 2 weeks after discontinuation) on visceral index of rats

3.5 pathological examination: the internal organs of rats in each dose group of the bone tuberculosis pill are not abnormal after the administration for 13 weeks and the stopping of the administration for 2 weeks. By visual observation, the thoracic cavity, abdominal cavity and brain of each group of rats have no obvious effusion, each organ has no edema and adhesion, the surface is smooth and has no nodules, and the body is regular and has no swelling; the tissue structure is normal, the cell differentiation is good, the pathological changes such as degeneration necrosis and the like do not exist, and the cells are arranged in order.

4 small knot

The tabellae ossis pill (prepared according to example 1) was administered to rats by gavage in three doses of 4.0g/kg body weight (15.56 times the clinical dose), 3.2g/kg body weight (12.44 times the clinical dose) and 2.4g/kg body weight (9.33 times the clinical dose), and was administered for 13 weeks and stopped for 2 weeks to observe the cumulative toxicity and delayed toxicity reaction that may occur to rats. The results show that: during administration and after stopping administration, the animals with the three doses of the bone tuberculosis pill have normal weight increase, normal blood and biochemical indexes, and main organ indexes and histopathological examination results. The pill has no obvious accumulative toxicity and delayed toxicity reaction to rats.

Clinical cases

Case 1:

zhang somewhere, woman, 50 years old, Shenyang Liaoning. The patient has no obvious inducement to the right hip pain in 11 months in 2015, can not walk, and is hospitalized for 5 days in a certain Jining hospital by 'right hip synovitis', and the effect is not ideal. Then the patient is diagnosed in Yanzhou Ministry hospital, the diagnosis is "right femoral head necrosis", and the anti-inflammatory and analgesic drug is orally taken for 20 days, the effect is poor, and the patient is diagnosed in the hospital after 2 months and 15 days in 2016. Admission symptoms are as follows: right hip pain, severe pain when moving, limited movement, inability to walk, difficulty in turning over, aggravation in cold, poor appetite, adequate sleep, normal defecation, pale red tongue, thin yellow coating and weak pulse.

Special examination: the right side of the relative length of the two lower limbs is shorter than the left side by 2cm, the middle point of the groin of the right side is pressed to be painful, the greater trochanter of the femur on the right side is knocked to be painful, the gluteus medius and the tensor fascia latae on the right side are pressed to be painful, the gluteus medius and the thigh muscles on the right side are atrophied, the sign of '4' on the right side cannot be completed, the sign of Thomas on the right side is positive, the sign of Elis. The right hip bends 80 degrees, abducts 10 degrees, adducts 0 degrees, internal rotation 0 degrees, external rotation 0 degrees, left hip mobility is acceptable, the muscle strength of the left lower limb is II grade, the grinding test of the left knee is positive, and the mobility is acceptable.

Auxiliary inspection: pelvis and chest positioning pieces: uneven bone density in the right femoral head and acetabulum, fuzzy trabecula, cystoid low-density shadow of bone, flat shape of the right femoral head, pointed bone structures at the edges of the femoral head and acetabulum, and narrowed hip joint space. The left lung portal has a high-density image like a block, rough edges, clear textures of the remaining two lungs, smooth diaphragm muscles, small cardiac image and clear and sharp rib diaphragm angles. Double hip MRI: 1. the osteonecrosis of the femoral head and acetabulum on the right side is high, and inflammatory lesions of the hip joint on the right side are not excluded; 2. double hip joint effusion (right side is famous); 3. edema of the upper right femur and the marrow of the right acetabular bone; 4. edema of the musculature surrounding the right hip joint and right iliac muscle. The traditional Chinese medicine diagnosis after admission is as follows: hip impediment, diagnosed west: 1. right hip osteoarthritis, 2. right hip infection? Tuberculosis?

The traditional Chinese medicine is used for treating the diseases of promoting qi and blood circulation, removing blood stasis and dredging collaterals and relieving swelling and pain, and the acupuncture point massage, the traditional Chinese medicine package and the warm acupuncture therapy are carried out on the medicines, and the cefuroxime sodium needle, the levofloxacin lactate, the Xiangdan needle and the mannitol needle are used for diminishing inflammation, promoting blood circulation and dehydrating to improve the effusion of the joint cavity and the Mizhiling tablet is used for improving the circulation of the lower limbs.

Double hip CT 2 month 19 days 2016: considering the possibility of right hip tuberculosis, avascular necrosis of the right femoral head and acetabulum is not excluded, and effusion of the right hip joint cavity is caused. Left knee MRI show: degenerative osteoarthritis of the left knee, osteonecrosis of the distal left femur and proximal tibia, left knee joint and suprapatellar effusion.

Supplementary diagnosis: osteonecrosis of the far end of the left femur and the near end of the tibia; tuberculosis of right hip joint.

The medicine prepared according to the invention in example 1 is orally taken for promoting blood circulation, removing obstruction in collaterals, reducing phlegm and resolving masses, and performing anti-tuberculosis treatment, 6g for one time and 3 times a day.

In 2016, 3 months and 4 days, patients complain of right hip pain reduction, more flexible activity and more advanced improvement of functions, obvious improvement of walking and turning over, reduction of left knee gall, normal liver and kidney function examination, normal ESR and CRP, and bilateral MRI: compared with the anterior plate, the right hip joint effusion is reduced more anteriorly, and the bone marrow edema is reduced more anteriorly. The patient is required to discharge from hospital, order to strictly lean on double crutches for walking, double lower limb skin traction, functional exercise and no fatigue, and continuously takes the anti-tuberculosis medicine. After 3 months of reexamination, the patient has no obvious pain, flexible movement and no relapse.

Case 2:

rely on somebody, woman, 66 years old, Guangdong province, Pingyuan county. The patients had no obvious induction of intermittent pain in the waist 20 years ago and were not treated. The clinical examination in local hospital in 2016 shows that tuberculosis of lumbar vertebra is suggested, and the thoracic hospital in Guangdong province takes the tuberculosis of lumbar vertebra as diagnosis and is treated by oral antituberculosis drugs for 2 months, so as to further diagnose and treat the tuberculosis in our hospital. Admission symptoms are as follows: pain in the waist, aggravation after exercise, mental clarity, appetite, sleep and defecation. Dark red tongue with thin and white coating and wiry and unsmooth pulse.

Special examination: the physiological curvature of the waist becomes shallow, and the activity of the waist is as follows: the anterior flexion is 70 degrees, the posterior extension is 10 degrees, the left and right lateral flexion is 15 degrees, the left and right rotation is 15 degrees, the spinous processes of the waists 3 and 4 and the right side pressing pain beside the spinous processes are not accompanied by the radiating pain of the lower limbs when the waist is tapped.

Auxiliary inspection: lumbar MRI: 1. the tuberculosis of the lumbar 2 vertebral body and the right pedicle of vertebral arch is considered, and the possibility of abscess of the right psoas major muscle is high; 2. the right kidney atrophied and hydrogled; 3. lumbar 4-5 disc herniation; 4. lumbar hyperosteogeny. Thoracic vertebra and lumbar vertebra CT: 1. lumbar 2 vertebral tuberculosis is considered; 2. degenerative change of thoracic and lumbar vertebrae; 3. thoracic 11, 12, lumbar 1 vertebral schmo tubercle; 4. the lumbar discs 3-4, 4-5 bulge and protrude.

The drug prepared according to example 2 of the present invention was orally administered 6g at a time 3 times a day, and the patient was asked to discharge after 2 weeks for relief of pain in the waist. After the patient is discharged from the hospital, the patient continues to take the medicine for 2 months, has no obvious pain in the waist and good activity, and continues to visit for 2 months without relapse.

Case 3:

iron in certain, male 55 years old, Henan Ye county. The patient develops right hip pain after 5 months of fatigue in 2015, presents persistent dull pain with soreness of waist and knees, is aggravated during walking and relieved after rest, is treated with lumbar intervertebral disc protrusion in local hospitals, has poor effect, is diagnosed in 2015 8 months to general hospitals of flat coal groups, and is examined as a double hip positive position tablet: necrosis of the right femoral head. The medicine is taken orally and has poor efficacy. And then to the provincial hospital of Henan to check the double hip MRI: 1. necrosis of right femoral head 2. marrow swelling of right hip joint, effusion of right hip joint, no systemic treatment. In 2016, 6 and 9 days, the patient got a diagnosis because of the aggravation of right hip pain after fatigue. Admission symptoms are as follows: lameness, right hip pain, limited mobility, difficulty in squatting, good appetite, poor sleep, and normal defecation. A red tongue with a yellow and thick coating and a slippery pulse.

Special examination: the tenderness is obvious in the groin on the right side, the percussion pain is generated at the greater trochanter on the right side, the muscle strength of the right lower limb is III grade, the thomas sign is positive, the right side whole castle sign is positive, the right side 4-shaped test is positive, the Ailis sign is positive, and the right hip mobility: abduction by 20 °, flexion by 80 °, internal rotation by 3 °, and external rotation by 3 °.

Auxiliary inspection: the positive axis position of the pelvis: the shapes of the double femur heads are different, the density of the right femoral head molars is uneven, the trabecular bone is fuzzy, a sac-like low-density image and a spot-shaped high-density image can be seen, and the right hip joint gap is narrowed. Double hip MRI: 1. right coxitis; 2. local osteonecrosis of right femoral head and right hip joint margin and detumescence of bone marrow; 3. right hip acetabulum effusion 4. right side ilium muscle and soft tissue edema around right hip joint.

The diagnosis is as follows: traditional Chinese medicine diagnosis: 1. bone erosion; 2. bone tuberculosis; and (3) Western diagnosis: 1. right femoral head necrosis; 2. tuberculosis of right hip joint.

After admission, the drug prepared according to example 4 of the present invention was orally administered 6g at a time, 3 times a day, and after 2 weeks, the pain of the patient was relieved, and the joint movement was improved, requiring discharge. After the patient is discharged from the hospital, the patient is continuously taken for 2 months and then is followed up, so that the pain is basically avoided, and the joint movement is good.

The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and it will be apparent to those skilled in the art that various modifications and variations can be made in the formulation and preparation process of the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. The pill for treating the tuberculosis of the bones and the joints is characterized by comprising a traditional Chinese medicine composition for treating the tuberculosis of the bones and the joints, wherein the traditional Chinese medicine composition for treating the tuberculosis of the bones and the joints is prepared from the following raw materials in parts by weight: 340-360 parts of rhizoma bolbostemmae, 140-160 parts of ligusticum wallichii, 140-160 parts of longan seeds, 290-310 parts of rhizoma smilacis glabrae and 40-60 parts of bulbus fritillariae cirrhosae;

every 100 parts of the traditional Chinese medicine composition is also added with 1-3 parts of starch and 0.155-0.165 part of microcrystalline cellulose.

2. Pill for the treatment of tuberculosis of bones and joints according to claim 1, characterized in that: 345 to 355 parts of rhizoma bolbostemmae.

3. Pill for the treatment of tuberculosis of bones and joints according to claim 1, characterized in that: 145-155 parts of ligusticum wallichii; 145-155 parts of longan seeds.

4. Pill for the treatment of tuberculosis of bones and joints according to claim 1, characterized in that: 295-305 parts of rhizoma smilacis glabrae; the fritillaria cirrhosa is 45-55 parts.

5. Pill for the treatment of tuberculosis of bones and joints according to claim 1, characterized in that: 350 parts of paniculate Bolbostemma rhizome; the ligusticum wallichii is 150 parts; 150 parts of longan seeds; 300 parts of glabrous greenbrier rhizome; the fritillaria cirrhosa is 50 parts.