CN1660399A - Medication for treating arthralgia due to wind-cold dampness and weary muscles and bones - Google Patents

Abstract

A Chinese medicine in the form of tablet or capsule for treating rheumatism, rheumatoid disease, and flaccidity of extremities is prepared from 21 Chinese-medicinal materials including pilose antler, coix seed, red peony root, astragalus root, etc through respective pulverizing, extracting in water and alcohol, proportional mixing, and preparing tablets or capsules.

Description

A kind of anemofrigid-damp arthralgia and muscles and bones soft medicine that withers for the treatment of

Technical field

The present invention relates to a kind of expelling wind and cold, it is active to dehumidify, the pharmaceutical composition of nourishing the liver and kidney, particularly relate to a kind of with the animals and plants Chinese crude drug be raw material make be used for the treatment of deficiency of the liver and kindey, anemofrigid-damp arthralgia, arthralgia, numb limbs and tense tendons, muscles and bones wither soft Chinese medicine and preparation thereof.

Background technology

At present, disclosed about treatment anemofrigid-damp arthralgia and muscles and bones wither soft medicine and preparation thereof, nineteen ninety-five applying date December 18 days is arranged, and publication number 1135909 " a kind of medicine for the treatment of hyperosteogeny, anemofrigid-damp arthralgia " is to be combined by multiple Chinese herbal medicine such as Radix Clematidis, Radix Saposhnikoviae, Semen Impatientis, Herba speranskiae tuberculatae, Fructus Liquidambaris, Fructus Canarii, Moschus, Sanguis Draxonis, Myrrha, the Radix Angelicae Dahuricae, Herba Asari, Semen Sinapis Albae, river taro, the Pseudobulbus Bletillae (Rhizoma Bletillae), Radix Notoginseng, Rhizoma Corydalis, Rhizoma Atractylodis, Pheretima, Semen Phaseoli, Rhizoma Cibotii, Radix Achyranthis Bidentatae, Fructus Evodiae, silkworm excrement, Radix Glycyrrhizae, maltoses; Arranged July 20 1997 applying date, and " plaster for rheumatism " of publication number 1171263 is a kind of externally applied ointments; Arranged November 26 1997 applying date, and publication number 1217930 " Chinese medicine preparation of treatment rheumatism, rheumatoid, lumbago and skelalgia, arthritis " selects Chinese medicine Radix Aconiti, Radix Aconiti Kusnezoffii, Fructus Mume, Flos Carthami, Radix Dipsaci, Radix Achyranthis Bidentatae, Fructus Chaenomelis, Radix Glycyrrhizae, Rhizoma Chuanxiong, Herba Taxilli to form; Arranged April 29 2003 applying date, and publication number 1480176 " the rheumatismal medicine of a kind of treatment " is made up of 20 kinds of Chinese medicines such as Herba Ephedrae, Radix Angelicae Pubescentis, Rhizoma Et Radix Notopterygii, Radix Saposhnikoviae, Herba Schizonepetae, Herba Asari, Radix Aconiti, Radix Aconiti Kusnezoffii, Rhizoma Atractylodis, four worms, Radix Dipsaci and Fructus Chaenomeliss.Existing in a word medicine and preparation medicine for external use thereof account for certain proportion, and oral medicine can strengthening the body resistance, and nourishing the liver and kidney can be treated muscles and bones and be withered soft then less.

Summary of the invention

So the object of the invention is treated anemofrigid-damp arthralgia and muscles and bones wither soft medicine and preparation thereof safely and effectively making with the Chinese crude drug of meticulously selecting.

In order to reach the foregoing invention purpose, solution of the present invention is based on motherland's medical science to anemofrigid-damp arthralgia and muscles and bones wither soft pathogenetic understanding and Therapeutic Principle, screening expelling wind and cold, active, the nourishing the liver and kidney Chinese crude drug of dehumidifying, according to the theory of Chinese medical science prescription, and extract the prescription elite, make it bring into play significant therapeutical effect.

Medicine of the present invention can be made (consumption is a weight portion) medicament by following component:

Caulis Sinomenii 80-100 part Ramulus Cinnamomi 20-40 part Radix Angelicae Pubescentis 20-40 part Rhizoma Et Radix Notopterygii 20-40 part

Radix Achyranthis Bidentatae 40-60 part Herba Taxilli 25-40 part Poria 25-40 part Radix Aconiti Lateralis Preparata 15-40 part

Radix Gentianae Macrophyllae 20-40 part Cornu Cervi Pantotrichum 4-8 part Radix Clematidis 40-60 part Semen Coicis 40-60 part

Radix Codonopsis 30-60 part Radix Astragali 30-60 part Fructus Lycii 40-80 part Rhizoma Atractylodis Macrocephalae 20-40 part

Radix Angelicae Sinensis 20-40 part Radix Paeoniae Rubra 20-40 part Radix Aucklandiae 20-30 part Radix Scutellariae 60-90 part

Rhizoma Corydalis 20-40 part

The optimum weight proportioning of medicine of the present invention is:

45 parts of 30 parts of Radix Achyranthis Bidentataes of 30 portions of Rhizoma Et Radix Notopterygiis of 30 parts of Radix Angelicae Pubescentiss of 90 parts of Ramulus Cinnamomi of Caulis Sinomenii

6 parts in 30 parts of Cornu Cervi Pantotrichums of 30 portions of Radix Gentianae Macrophyllae of 30 parts of Radix Aconiti Lateralis Preparatas of 30 parts of Poria of Herba Taxilli

60 parts of 30 parts of Fructus Lycii of 30 parts of Radixs Astragali of 45 parts of Radix Codonopsis of 45 portions of Semen Coiciss of Radix Clematidis

90 parts of 24 parts of Radix Scutellariaes of 30 parts of Radix Aucklandiae of 30 parts of Radix Paeoniae Rubra of 30 parts of Radix Angelicae Sinensis of the Rhizoma Atractylodis Macrocephalae

30 parts of Rhizoma Corydalis

Medicine of the present invention is characterized in that said medicament is a said dosage form on any pharmaceutics.

Medicine of the present invention is characterized in that said medicament is tablet, capsule.

With above-mentioned each component preparation cost invention medicine production method be: Cornu Cervi Pantotrichum, Semen Coicis, Radix Aconiti Lateralis Preparata, Rhizoma Corydalis, Radix Codonopsis, Radix Paeoniae Rubra are ground into fine powder, Poria, the Radix Astragali, Fructus Lycii, Radix Achyranthis Bidentatae, Herba Taxilli, twice of water extraction of Radix Clematidis, the each extraction 1.5 hours, extract 98-102 ℃ of water temperature, extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.40-1.45 (60 ± 5 ℃ heat survey); The Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Radix Angelicae Pubescentis, Rhizoma Et Radix Notopterygii, Radix Gentianae Macrophyllae, Ramulus Cinnamomi, the Radix Aucklandiae, Radix Scutellariae, Caulis Sinomenii are with twice of ethanol extraction, the each extraction 1.5 hours extracted 78-82 ℃ of temperature, and extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.30-1.35 (60 ± 5 ℃ heat survey); Described fine powder above two kinds of thick pastes add, mixing is made bulky grain, vacuum drying, dry substance is ground into fine powder, and mixing is made said dosage form on any pharmaceutics.

Treatment anemofrigid-damp arthralgia of the present invention and muscles and bones wither soft medicine (also claim " rheumatalgia sheet ") studies have shown that through pharmacological experiment research, long term toxicity test data and clinical etc. have expelling wind and cold, active, the nourishing the liver and kidney effect of dehumidifying, remarkable to treating above-mentioned curative effect of disease, and have no side effect; Now experimentation is described below.

The pharmacological research data that the rheumatalgia sheet is relevant with therapeutical effect

The rheumatalgia sheet is a pure Chinese medicinal preparation, and its function is expelling wind and cold, active, the strengthening the body resistance of dehumidifying, is used for various types of cold rheumatoid joint pains, aching pain in waist and back and numb limbs and tense tendons.According to the as above property of medicine, the pharmacological evaluation of the following several respects of ad hoc meter is summarized as follows.

1 experiment material

This laboratory animal source: Beijing medical courses in general institute animal center.

Sample source: Tianjin Tongrentang Co., Ltd. (former Tianjin Tongrentang Pharmaceutical Factory).

People's clinical usual amounts: a 6-8 sheet, every day three times.

2 methods and result

2.1 acute toxicity testing (LD ₅₀)

Get 40 of body weight 18-20 gram Kunming kind healthy mices, male and female half and half, female person is infertile, is divided into three administration group (30g/Kg at random, 15g/Kg, 7.5g/Kg), route of administration is irritated stomach, gives the rheumatalgia sheet among one day at twice, each 1ml/ only, observed seven days continuously after the administration, observed result shows: it is more normal that mice is taken each dosage animal drinking-water behind the rheumatalgia sheet, diet and activity, hair color and matched group, do not see any toxic reaction and also none Mus death.

2.2 influence to the mouse ear capillary permeability

Get 80 of male mice in kunming, body weight is 20-22g, is divided into 4 groups at random, comprises rheumatalgia sheet group, hydrocortisone group, matched group, every group of 20 mices, the administration volume is the 0.2ml/10g body weight, and one week of oral administration is in administration last day after 2 hours, press the bibliographical information method, cause scorching liquid with the Oleum Tiglii mixing and (include Oleum Tiglii 2%, dehydrated alcohol 20%, absolute ether 78%.) being applied to two sides, left ear front and back, O.05ml every Mus ear is coated with, and makes its inflammation swelling.After four hours the disconnected cervical vertebra of animal is put to death at interval, lay round auricle at the same position of Mus ear respectively, weigh left and right sides ear weight rapidly in the balance, and obtain two ear weight differences with the scleral perforation device.Learn by statistics and handle, and calculate inhibitory rate of intumesce.

Table 1: the rheumatalgia sheet is to the influence of mouse ear capillary permeability

Group	Number of elements	Dosage	Average swelling weight (mg)	Suppression ratio	The t value	The p value
							The rheumatalgia sheet	???20	???8g/Kg	????14.9±1.96	???30％	?13.47	???＜0.01
???20	???4g/Kg	????15.45±2.88	???27％	?8.73	???＜0.01
						Hydrocortisone		???20	???10mg/Kg	????7.65±3.24	???64％	?18.27	???＜0.01
Matched group	???20	Distilled water	????21.3±0.82

The result shows: compare with matched group, the rheumatalgia sheet can make the Mus ear thickness of smearing Oleum Tiglii have significantly to alleviate (p＜0.01), and hydrocortisone also can make the Mus ear swelling of smearing Oleum Tiglii alleviate, and compares significant difference (p＜0.01) with matched group.By table as seen, the rheumatalgia sheet has the effect of the capillary permeability of reduction.

2.3 influence to the mice granuloma induced by implantation of cotton pellets

Get 30 of healthy male mices, body weight 25-28g is divided into three groups, gives one of every aseptic cotton balls of subcutaneous each the heeling-in 7.5mg of mice both sides web portion earlier, gives rheumatalgia sheet 8g/Kg then every day respectively, hydrocortisone 10mg/Kg and one week of normal saline gastric infusion.Put to death mice after the 7th day, carefully isolate the granuloma induced by implantation of cotton pellets piece, precision takes by weighing weight in wet base, takes by weighing dry weight after drying again; Relatively the difference between administration group, hydrocortisone group and matched group the results are shown in Table.

Table 2: to the influence of mice granuloma induced by implantation of cotton pellets

Group	Number of animals	Dosage	Granuloma induced by implantation of cotton pellets average weight (mg)
					Weight in wet base	Dry weight
			The rheumatalgia sheet	????10			??8g/Kg	??68±14.9	??21.8±3.9
Hydrocortisone	????10	??10mg/Kg			??53.5±6.26	??19±1.55
			Matched group	????10			Normal saline	??102±18.2	??32.1±5.7

The result shows: the rheumatalgia sheet is compared with the normal saline group with the subcutaneous granuloma induced by implantation of cotton pellets of the mice of hydrocortisone group, and inhibitory action is in various degree all arranged, and P all＜0.001.Prompting: the rheumatalgia sheet has the effect that suppresses cott on pellet-induced granuloma formation.

2.4 the rheumatalgia sheet is to the influence of rat albumen arthritis

Get 40 of male rats about body weight 150g, be divided into 4 groups at random, comprise rheumatalgia sheet 8g/Kg, two dosage groups of 4g/Kg.Matched group gastric infusion every day once, continuous 8 days; The hydrocortisone group was in beginning administration in the 5th day, and route of administration is the filling stomach.Each is organized and used the Ovum Gallus domesticus album moulding after after the last administration 1 hour, with the right ankle of 0.1ml fresh albumen subcutaneous injection in rat, measure the girth of right ankle joint before and after the moulding with tape, with left ankle joint is normal value, difference with left and right sides ankle joint is the index of arthroncus degree, and relatively administration group and matched group have or not significant difference (seeing Table 3).

Table 3: the rheumatalgia sheet is to the influence of rat albumen arthritis

Group	Number of animals	Animal dosage	Different time swelling degree (cm) after the administration
								30 minutes	1 hour	2 hours	3 hours	4 hours
			The rheumatalgia sheet	???10	?8g/Kg	???0.41± ??????0.25 *	??0.34± ?????0.19 *						??0.51± ?????0.10 *	??0.23± ?????0.08 *	??0.28± ?????0.17 *
???10	?4g/Kg	???0.61± ??????0.10 *						??0.52± ?????0.08 *	??0.475 ??±0.1 *	??0.41± ?????0.16 *	??0.38± ?????0.08 *
				Hydrocortisone	???10	?10mg/Kg	???0.60± ??????0.20 **					??0.51± ?????0.12 *	??0.51± ?????0.10 *	??0.25± ?????0.14 **	??0.36± ?????0.09 *
Matched group	???10	Normal saline	???0.86± ??????0.23					??0.85± ?????0.15	??0.84± ?????0.21	??0.71± ?????0.19	??0.62± ?????0.15

^*P＜0.01?? ^**P＜0.05

The result shows: the rheumatalgia sheet has the obvious suppression effect to the redness of albumen arthritis, and the effect of high dose administration group is obvious than low dose group.

2.5 the analgesic activity of rheumatalgia sheet

30 of mices, body weight 18-20g femalely is divided into three groups at random, stimulate temperature to remain on 55 ± 0.5 ℃, normal mouse is placed on the thermometal dish, as threshold of pain index, selects the responsive stable mice of reaction and be used for test from mice rear foot contact hot plate to the time till the metapedes of licking.The relatively variation of the threshold of pain before and after the administration the results are shown in Table 4.

Table 4: the rheumatalgia sheet is to the influence of mice threshold of pain hot plate method

Group	Number of animals	Animal dosage	Threshold value (second) before the administration	Threshold value after the administration (second)
								1 hour	1.5 hour	2 hours	3 hours
				The rheumatalgia sheet	???10	??8g/Kg	???23.1± ??????3.7					??36.8± ?????5.8	???38.8± ??????4.7	??40.8± ?????5.18	???52± ??????13.8
???10	??4g/Kg	???23.6± ??????4.1	??36.6± ?????6.7					???37.2± ??????5.9	??38.1± ?????7.6	???45.9± ??????12.3
					Matched group	???10	Normal saline				???22.7± ??????4.9	??23.3± ?????5.1	???23.4± ??????3.7	??23.7± ?????4.8	???26.5± ??????6.34

The result shows: each the group with administration before compare, two dosage groups of rheumatalgia sheet can obviously improve the mice threshold of pain.1-3 hour the threshold of pain is than the equal P in the preceding threshold of pain of administration＜0.001 after the administration of two dosage groups of rheumatalgia sheet.The threshold of pain does not have marked difference before and after the matched group administration.

2.6 the rheumatalgia sheet is to the influence of laboratory animal hind leg blood flow

Get 18 of the healthy wistar rats of 200-250g, the male and female dual-purpose, female person is infertile, divide equally two groups at random, the administration treated animal is irritated the raw pain sheet of stomach disorder due to wind pathogen 8g/Kg every day, continuous 10 days, control animals gives the isodose distilled water, two treated animals all the 11st day with pentobarbital sodium anesthesia (40mg/Kg body weight) after, dorsal position is fixed in the Mus platform, cuts off left and right sides hind leg upside skin, and carefully the bipolar needle electrode of the BE-ND that will in advance handle well is gone in the musculi gracilis 1.5mm with 30 ° of angle skewers, and with butterfly AgCL indifferent electrode near placing subcutaneous after, two electrodes are connected in after RBF-II type electricity Jie's formula tissue blood flow's instrument (Biomedical Sciene Co.Ltd, Japan) stablizes 20 minutes through electrode input casket, press literature method mensuration tissue blood flow, calculate tissue blood flow's amount, get the meansigma methods of the close measured value of secondary.The result shows, through rheumatalgia sheet 8g/Kg body weight/day, after oral 10 days, its hind leg muscular tissue blood flow (76.8 ± 42.8) has remarkable increase P＜0.05 than control animals hindlimb muscle tissue blood flow amount (32.1 ± 11.9), shows that the rheumatalgia sheet has the effect of obvious increase normal rat hindlimb muscle tissue blood flow.

3 brief summaries

We have designed according to the property of medicine of this medicine, and mouse knoting oil is coated with the ear stimulus method and subcutaneous cotton pellet method is observed its antiinflammation, and the result shows that it has good anti-inflammation detumescence effect.

The rheumatalgia sheet has the obvious suppression effect to albumen arthritis, and by the observation to analgesic experiment, as seen this medical instrument significantly increases threshold of pain effect, and is consistent with the curative effect of clinical treatment aching pain in waist and back; Rat hindlimb muscular tissue blood flow there is tangible increase effect, this helps limb muscle to organize microcirculatory improvement undoubtedly and organizes oxygen supply to increase, and make refuse be easy to metabolism and elimination, obviously can help the treatment of patient's numb limbs and tense tendons and the progressively recovery of function.

Acute toxicity is higher than 200 times of the clinical usual amounts of people, does not have any toxic reaction.

Further prove the medicine of all kinds of cold rheumatoid joint pains of a kind of really comparatively ideal treatment of rheumatalgia sheet in a word by above experimental result.

Rheumatalgia sheet subchronic toxicity testing

1 method and result

Select 80 body weight 100-115 gram for use, 7-8 age in week healthy wistar rat, male and female half and half are divided into following four groups, comprise three dosage groups of matched group and rheumatalgia sheet (15g/Kg, 7.5g/Kg, 3.75g/Kg).

Laboratory animal room adopts air-conditioning attemperation (20 ± 2 ℃), set time every day gastric infusion.Administration is 6 days weekly, and drug withdrawal one day is weighed weekly once, adjusts dosage, in the administration process, and writes down the behavior of diet and animal at any time, and experiment is three months, after get the every biochemical indicator of hematometry and get each internal organs and do pathologic finding through 20% formaldehyde fixed.Every result is shown in the following table (administration time is three months).

Annotate: animal origin Beijing medical courses in general institute animal center

Sample source Tianjin Tongrentang Pharmaceutical Factory (Tianjin Tongrentang Co., Ltd.)

Table 1: the rheumatalgia sheet is to the influence of rat hemogram

Group	Number of animals	Dosage	Hemogram
						Erythrocyte ten thousand/mm 3	Leukocyte ten thousand/mm 3	Platelet ten thousand/mm 3
			Matched group	????20	??-				??695.47± ????32.26	???12.685± ??????2.410	???46.23± ??????10.18
High dose	????20	??15g/Kg				??686.25± ????46.76	???12.008± ??????2.935	???44.14± ??????12.16
			Middle dosage	????20	??7.5g/Kg				??678.84± ????59.28	???12.340± ??????3.430	???43.9±6.5
Low dosage	????20	??3.75g/Kg				??701.0± ?????36.5	???12.115± ??????2.860	???43.0±8.3

Table 2: to the influence of hepatic and renal function

Group	Number of animals	The % of liver function unit (SGPT) ± SD	Renal function mg% (NPN) X ± SD
				Matched group	?????20	???25.9±4.31	??12.2±2.40
High dose	?????20	???26.15±6.58	??9.42±2.42
				Middle dosage	?????20	???26.12±8	??11.01±2.97
Low dosage	?????20	???26.26±4.52	??10.64±3.43

Table 3: to the influence of hemoglobin

Table 4: the rheumatalgia sheet is to the influence of rat body weight

Group		Matched group	High dose	Middle dosage	Low dosage
						Dosage		??--	???15g/Kg	???7.5g/Kg	???3.75g/Kg
Body weight is observed before and after the administration	One week	??93.3±13	???94.8±16	???102.8±10.3	???96.4±12.4
						Two weeks	??122.6±24.7	???101±13.3	???114.2±11.5	???110.8±14.6
	Three weeks	??155.3±24.1	???110.2±14.3	???129.6±14.9	???123.8±18.8
						All around	??180.7±25.8	???132.1±21	???160.3±20.4	???153.8±28.9
	Five weeks	??190±29.7	???151±19.2	???177.6±20.8	???175.8±30.2
						Six weeks	??200±31.4	???163.1±20.6	???187.7±21.0	???188.5±30.9
	Seven weeks	??212±30.3	???194.6±14.7	???196.8±38.5	???199.7±22.4
						Eight weeks	??221±35.6	???195±26.6	???211.3±27.3	???210.1±27.2
	Nine weeks	??232.2±34.8	???199.2±26.7	???217.3±32.9	???197.8±25.7
						Ten weeks	??243.8±27.9	???206.1±26	???222.4±33.2	???212.5±25.1
	11 weeks	??243.4±27.9	???217.1±23.7	???236±26	???226±28
						12 weeks	??245.7±36	???230±21.1	???248±28	???238±25

By table 1-4 as seen, the rheumatalgia sheet does not all have obvious influence to rat hemogram, liver, renal function and body weight, and each dosage treated animal does not all have any toxic reaction in the administration process.Animal skin gloss, and diet, drinking-water, eyes, breathing, circulation, extremity activity are all normal, dead animal do not occur.

2 conclusions

The long-term toxicity test of rheumatalgia sheet shows, high, medium and low three dosage groups, biochemistry, pathology and other every index are compared with matched group and are had no significant change, point out long-term low dose to be equivalent to 25 times and heavy dose of 100 times of being equivalent to clinical consumption of clinical consumption, all there is not any toxic reaction, so can under usual amounts, take for a long time.This medicine is safe and reliable, non-toxic reaction.

The morphologic observation of rheumatalgia sheet subchronic disease reason

1 experimental technique

Get the healthy rat about body weight 100g, male and female half and half are divided into four groups, every group of 20 Mus.High dose is irritated stomach and is given rheumatalgia sheet 15g/Kg, middle dosage 7.5g/Kg, and low dosage 3.75g/Kg is with establishing matched group.Each is organized and is administered once every day, and continuous three months, do not see the animal untoward reaction during the administration, comprise hemogram, liver,spleen,kidney function no abnormality seen.Experiment finishes, and puts to death animal, dissect core, liver, spleen, lung, kidney, gastrointestinal, 10%Formalin fix conventional film-making, HE dyes.

Observed result under 2 mirrors

2.1 the heart

The contrast cardiac muscle in length and breadth texture as seen, the easy red stain of the slight cloudy swelling of muscle fiber, a light weight degree hyperemia, round cell soaks into, and removes high dose one Mus and is the interstitial myocarditis reaction, all the other each treated animals and matched group do not have significant difference.

2.2 liver

Contrast lobules of liver clear in structure, the liver cell element marshalling, the expansion that central vein has, blood stasis, the part of hepatocytes cloudy swelling, water sample becomes, cell infiltration in various degree, the biliary ductuli hypertrophy, each administration group is similar with matched group.

2.3 spleen

Each experimental group spleen is organized red pulp, white pulp clear in structure, all the slight blood stasis in visible center.

2.4 lung

Each experimental group animal alveolar wall varying degree thickens hyperemia, and inflammatory cell is filled, and local edema due to disorder of QI is hemorrhage, all suffers from the different interstitial pneumonias of degree.

2.5 kidney

The hyperemia of contrast glomerule, slightly enlargement, matter hyperemia between renal tubules,convoluted epithelium cloudy swelling, a small amount of round cell soaks into, and removes high dose one Ren Mus broad-mouthed receptacle for holding liquid transitional epithelium hypertrophy, and focus of infection is arranged, other each treated animal and matched group no significant difference.

2.6 gastrointestinal

Each laboratory animal gastrointestinal mucosa is complete, the lamina propria moderate, and lymphocyte and intiltration of acidophilic leukocyte, mucosa are congested down, Mild edema.

3 brief summaries

3.1 this experiment gives the rheumatalgia sheet, each internal organs of rat do not see that the drug-induced pathologic changes.

3.2 testing each treated animal, this all suffers from chronic infection, so that some pathology pathological changes of secondary, contrast and administration group no significant difference.

The clinical observation of rheumatalgia sheet treatment rheumatoid arthritis

Rheumatoid arthritis is called for short RA, is one of generally acknowledged difficult and complicated illness of Chinese and western medicine, does not still have ideal effective Therapeutic Method at clinicing aspect.We use rheumatalgia sheet treatment RA164 example in recent years, and compare with Radix Tripterygii Wilfordii tablet, and the result is comparatively satisfied, now is reported as follows.

1 clinical data

1.1 the sick diagnostic criteria of traditional Chinese medical science numbness

The a main clinical manifestation: position pain such as joint skin, muscles and bones or swelling, morning deadlock, numbness is weighing or joint stuffiness, joint swelling deformation very then, tetanic can not stretching, amyotrophy, inability to stand up straightly as if the function of heels is replaced by the sacral bone, hunchback etc.

B etiology and pathogenesis characteristics: battalion defends deficiency, negative and positive of qi and blood imbalance or deficiency of both the liver and kidney, and weakened body resistance and evil gathering felt exopathogen or double blood stasis again, and the turbid or wound of expectorant causes.

C characteristics of incidence: how relevant with climate change.

D sex age characteristics: good sending out in person between twenty and fifty, the woman is more than the man.

The e physico-chemical examination:

(1) anti-O increases or erythrocyte sedimentation rate speeds or the rheumatoid factor positive or immunoglobulin increase.

(2) the visible sclerotin infringement of X line.

Possess three of above-mentioned a, b, e, can make a definite diagnosis [the clinical research guideline that this standard is new drug (Chinese medicine) treatment numbness disease] in conjunction with c or d item.

1.2 Western medicine diagnose standard (1987 American Rheumatism Association in 51 rheumatism annual meetings, revise standard).

At least 1 hour (〉=6 week) of a deadlock in morning.

B3 or 3 above swollen joints (〉=6 week).

C wrist metacarpophalangeal joints or proximal interphalangeal joint swell (〉=6 week).

D symmetry swollen joint (〉=6 week).

The e subcutaneous nodule.

F hands X-ray film changes.

The gRF positive (titer＞1: 32).

Typical case RA possesses above 7; Certainly RA possesses more than 5; Possible RA possesses more than 3.

1.3 standard by stages

By the standard that CAIM (Chinese Association Of Integrative Medicine) rheumatism Professional Committee formulates, be divided into early stage, mid-term, late period.This observes the RA246 example altogether, rheumatalgia sheet observation group 164 examples wherein, early stage 86 examples, mid-terms 60 example, late periods 18 example; Radix Tripterygii Wilfordii tablet matched group 82 examples, early stage 46 examples, mid-terms 26 example, late periods 10 example.

1.4 physical data

A sex: observation group's 164 examples, male 28 examples, women 136 examples; Matched group 82 examples, male 18 examples, women 64 examples.

The b age: observation group's age is at 17-46 between year, 35.50 ± 17.32 years old mean age; The matched group age is at 19-54 between year, 37.36 ± 21.57 years old mean age.

The c course of disease: the shortest person of the patient of the observation group course of disease is 3 months, and elder is 7.36, average out to 13.24 ± 9.35 months; The shortest person of matched group is 3.4 months, and elder is 9.30, average out to 12.78 ± 9.35 months.Physical data relatively sees table 1 for details between two groups.

Table 1: two groups of patient's physical data are (X ± S) relatively

Two groups of contrast indifferences.

2 observational techniques and observation item

2.1 observational technique

2.1.1 grouping: clinically be divided into two groups at random, observation group and matched group.

2.1.2 medicine for treatment: observation group's clothes rheumatalgia sheet, each 6-8 sheet, serve on 2 months at every day 3 times; Matched group is taken Radix Tripterygii Wilfordii tablet (production of Huangshi pharmaceutical factory), and each 0.2g, serve on 2 months at every day 3 times; Evaluate curative effect at last.

2.1.3 other medications: do not take other antirheumatic during taking this medicine, as have other disease concurrently, medicine continues to take.

2.2 observation index

2.2.1 symptom and sign: mainly observe pain, swelling and the functional activity index in pathological changes joint, the standard that the index standards of grading are formulated with reference to CAIM (Chinese Association Of Integrative Medicine) rheumatism Professional Committee.

0 grade of pain index: no pain.

The I level: motionless not bitterly, the activity hypodynia.

The II level: motionless also pain, activity pain increases the weight of.

The III level: sharp ache, stiff.

0 grade of swelling index: no swelling.

I level: be lower than bone mark.

II level: flat bone mark.

III level: be higher than bone mark.

0 grade of joint motion index: joint motion is not limited.

The I level: many limits are less than 1/5.

The II level: many limits are less than between the 1/5-2/5.

III level: limit greater than 2/5 more.

2.2.2 laboratory indexes: observe rheumatoid factor and erythrocyte sedimentation rate and change.

2.2.3 the X line changes: some cases is observed the X line and is changed.

3 observed results

3.1 clinical index improves situation: clinical index improves situation and sees Table 2 and table 3 respectively before and after observation group and the treatment of control group, and two groups of treatment back exponential integral decline averages relatively see Table 4.

Table 2: several clinical indexs improvement in observation group treatment back situation (X ± S)

Example number pain index swelling index joint motion index

Treat preceding 164 2.19 ± 0.95 1.62 ± 0.74 2.27 ± 1.06

Treatment back 164 1.52 ± 0.74 ^*1.17 ± 0.68 ^*1.73 ± 0.95 ^*

Annotate: compare after the treatment with before the treatment ^*P＜0.05

Table 3: several clinical indexs improvement situations after the treatment of control group (X ± S)

Example number pain index swelling index joint motion index

Treat preceding 82 2.29 ± 0.99 1.76 ± 0.78 2.31 ± 1.39

Treatment back 82 1.76 ± 0.78 ^*1.32 ± 0.67 ^*1.79 ± 0.96 ^*

Annotate: compare after the treatment with before the treatment ^*P＜0.05

Table 4: index decreased average comparison after two groups of treatments (X ± S)

Example number pain index swelling index joint motion index

Treat preceding 164 0.72 ± 0.31 0.54 ± 0.38 0.68 ± 0.27

Treatment back 82 0.63 ± 0.41 0.43 ± 0.29 0.57 ± 0.32

Annotate: two groups are compared zero difference

3.2 laboratory indexes improves situation: observation group is 47.73 ± 21.35 before the erythrocyte sedimentation rate treatment, is 26.13 ± 19.20 after the treatment, and relatively there is significance meaning P＜0.01 front and back; Being 49.52 ± 24.13 before the treatment of control group, is 27.98 ± 21.50 after the treatment, and relatively there is significance meaning P＜0.01 front and back; Erythrocyte sedimentation rate decline average observation group is 22.05 ± 11.39, and matched group is 23.19 ± 12.64, two groups of relatively zero differences.Contrast sees Table 5 before and after the rheumatoid factor treatment.No significant difference between two groups.

Table 5: the rheumatoid factor comparison of turning out cloudy before and after two groups of treatments

The negative number negative conversion rate of RF number positive treatment back RF before the treatment

Observation group 102 48 47%

Matched group 58 28 48.2%

3.3 the X line changes: there are 112 examples in observation group, matched group has 54 examples to carry out the contrast of X line before and after treatment, and the result shows that nothing obviously changes.

3.4 curative effect: with reference to the standard that CAIM (Chinese Association Of Integrative Medicine) rheumatism Professional Committee formulates, for ease of statistics, curative effect is divided into clinical cure, produce effects, improvement, invalid.

The a clinical cure: symptom all disappears, and it is normal that functional activity recovers, and main physico-chemical examination, erythrocyte sedimentation rate, rheumatoid factor, anti-" O " recover normal, and X toe-in fruit is normal or recover normal.

The b produce effects: symptomatology is eliminated or cardinal symptom is eliminated, and function of joint is recovered substantially, can participate in operate as normal and work, and main physico-chemical examination, erythrocyte sedimentation rate, rheumatoid factor, anti-" O " are normal substantially.

C takes a turn for the better: cardinal symptom is eliminated substantially, main function of joint is recovered substantially or is had made marked progress, can't take care of oneself, transferring to lives can take care of oneself, perhaps lose the job or work capacity transfers work to and ability to work is recovered to some extent, main physico-chemical examination, erythrocyte sedimentation rate, rheumatoid factor, resist " O " that improvement is arranged.

D is invalid: with compare before the treatment, each side does not all have progressive or changes.

Observation group and matched group curative effect relatively see Table 6, no significant difference between the curative effect.

Table 6: two groups of curative effects relatively

It is invalid that example number clinical cure produce effects takes a turn for the better

Observation group 164 18 (10.9%) 86 (52.4%) 48 (29.4%) 12 (7.3%)

Matched group 82 8 (9.8%) 41 (50%) 25 (30.4%) 8 (9.8%)

3.5 side reaction: side reaction and side effect take place in observation group's none example during medicine for treatment, and matched group side effect during medicine for treatment is more, sees Table 7.

Table 7: the side effect situation appears in matched group

Example number stomachache poor appetite abdominal distention constipation menolipsis abnormal liver function renal dysfunction

Matched group 84 26 42 30 14 16 12 0

Percentage rate 30.9 50 35.7 16.7 19 14.2 0

4 brief summaries

Rheumatoid arthritis is the disease of difficulty clinically, and no matter traditional Chinese medical science doctor trained in Western medicine does not still have the specific treatment method at present, and the active drug of therefore seeking the treatment rheumatoid arthritis is still the urgent problem of current medical circle.This group is observed the example with rheumatalgia sheet treatment RA164, and and Radix Tripterygii Wilfordii tablet treat 82 examples and compare, from observed result, rheumatalgia sheet and Radix Tripterygii Wilfordii tablet treatment RA, clinical symptoms, sign index are had clear improvement (P＜0.01), and the rheumatoid factor negative conversion rate is respectively 47% and 48.2%, and total effective rate is respectively 92.7% and 90.5%, cure-remarkable-effectiveness rate is respectively 63.3% and 59.5%, has obtained satisfied curative effect.Between two groups relatively, the difference that no matter is that there are no significant from aspects such as symptom, sign index, laboratory indexes, clinical effectiveness.

From side reaction and side effect, the rheumatalgia sheet significantly is better than Radix Tripterygii Wilfordii tablet.Rheumatalgia sheet group is treated 164 examples, side effect takes place in none example, and Radix Tripterygii Wilfordii tablet generation side effect is more, and nearly 1/2nd patient has the gastrointestinal irritation symptom, as poor appetite, stomachache, abdominal distention etc., and there are 16 routine women patients that menolipsis takes place, accounting for 19%, 12 routine abnormal liver function, mainly is that the transaminase slightly raises, after drug withdrawal 3-6 month, the basic recovery normally.

In sum, the two is similar on therapeutic effect for rheumatalgia sheet and Radix Tripterygii Wilfordii tablet, but the rheumatalgia sheet is a pure Chinese medicinal preparation, aspect toxicity, side effect, significantly be better than Radix Tripterygii Wilfordii tablet, therefore the rheumatalgia sheet is a kind of pure Chinese medicinal preparation of treatment rheumatoid arthritis of effective, safe, inexpensive, taking convenience, has wide practical use clinically.

The specific embodiment

Embodiment 1 preparation tablet

Take by weighing raw material by following weight proportion:

Caulis Sinomenii 90g Ramulus Cinnamomi 30g Radix Angelicae Pubescentis 30g Rhizoma Et Radix Notopterygii 30g Radix Achyranthis Bidentatae 45g

Herba Taxilli 30g Poria 30g Radix Aconiti Lateralis Preparata 30g Radix Gentianae Macrophyllae 30g Cornu Cervi Pantotrichum 6g

Radix Clematidis 45g Semen Coicis 45g Radix Codonopsis 30g Radix Astragali 30g Fructus Lycii 60g

Rhizoma Atractylodis Macrocephalae 30g Radix Angelicae Sinensis 30g Radix Paeoniae Rubra 30g Radix Aucklandiae 24g Radix Scutellariae 90g

Rhizoma Corydalis 30g

Preparation method: Cornu Cervi Pantotrichum, Semen Coicis, Radix Aconiti Lateralis Preparata, Rhizoma Corydalis, Radix Codonopsis, Radix Paeoniae Rubra are ground into fine powder, Poria, the Radix Astragali, Fructus Lycii, Radix Achyranthis Bidentatae, Herba Taxilli, twice of water extraction of Radix Clematidis, the each extraction 1.5 hours, extract 98-102 ℃ of water temperature, extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.40-1.45 (60 ± 5 ℃ heat survey); The Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Radix Angelicae Pubescentis, Rhizoma Et Radix Notopterygii, Radix Gentianae Macrophyllae, Ramulus Cinnamomi, the Radix Aucklandiae, Radix Scutellariae, Caulis Sinomenii are with twice of ethanol extraction, the each extraction 1.5 hours extracted 78-82 ℃ of temperature, and extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.30-1.35 (60 ± 5 ℃ heat survey); Described fine powder above two kinds of thick pastes add, mixing is made bulky grain, vacuum drying, dry substance is ground into fine powder, and mixing is granulated, and tabletting is made 1046 (every 0.30g contains crude drug 0.76g), coating, promptly.Usage and dosage, oral, a 6-8 sheet, 2 times on the one; The careful usefulness of hypertension.

Embodiment 2 preparation capsules

Take by weighing raw material by following weight proportion

Caulis Sinomenii 80g Ramulus Cinnamomi 20g Radix Angelicae Pubescentis 20g Rhizoma Et Radix Notopterygii 20g Radix Achyranthis Bidentatae 40g

Herba Taxilli 25g Poria 25g Radix Aconiti Lateralis Preparata 15g Radix Gentianae Macrophyllae 20g Cornu Cervi Pantotrichum 4g

Radix Clematidis 40g Semen Coicis 40g Radix Codonopsis 30g Radix Astragali 30g Fructus Lycii 40g

Rhizoma Atractylodis Macrocephalae 20g Radix Angelicae Sinensis 20g Radix Paeoniae Rubra 20g Radix Aucklandiae 20g Radix Scutellariae 60g

Rhizoma Corydalis 20g

Preparation method

Cornu Cervi Pantotrichum, Semen Coicis, Radix Aconiti Lateralis Preparata, Rhizoma Corydalis, Radix Codonopsis, Radix Paeoniae Rubra are ground into fine powder, Poria, the Radix Astragali, Fructus Lycii, Radix Achyranthis Bidentatae, Herba Taxilli, twice of water extraction of Radix Clematidis, the each extraction 1.5 hours, extract 98-102 ℃ of water temperature, extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.40-1.45 (60 ± 5 ℃ heat survey); The Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Radix Angelicae Pubescentis, Rhizoma Et Radix Notopterygii, Radix Gentianae Macrophyllae, Ramulus Cinnamomi, the Radix Aucklandiae, Radix Scutellariae, Caulis Sinomenii are with twice of ethanol extraction, the each extraction 1.5 hours extracted 78-82 ℃ of temperature, and extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.30-1.35 (60 ± 5 ℃ heat survey); Described fine powder above two kinds of thick pastes add, mixing is made bulky grain, vacuum drying, dry substance is ground into fine powder, and mixing sieves, and is encapsulated, makes 603 (every 0.40g contains crude drug 1.01g), promptly.Usage and dosage, oral, a 5-6 grain, 2 times on the one; The careful usefulness of hypertension.

Claims (5)

1, a kind of anemofrigid-damp arthralgia and muscles and bones soft medicine that withers for the treatment of is characterized in that it being the medicament of being made by following materials of weight proportions

Caulis Sinomenii 80-100 part Ramulus Cinnamomi 20-40 part Radix Angelicae Pubescentis 20-40 part Rhizoma Et Radix Notopterygii 20-40 part

Radix Achyranthis Bidentatae 40-60 part Herba Taxilli 25-40 part Poria 25-40 part Radix Aconiti Lateralis Preparata 15-40 part

Radix Gentianae Macrophyllae 20-40 part Cornu Cervi Pantotrichum 4-8 part Radix Clematidis 40-60 part Semen Coicis 40-60 part

Radix Codonopsis 30-60 part Radix Astragali 30-60 part Fructus Lycii 40-80 part Rhizoma Atractylodis Macrocephalae 20-40 part

Radix Angelicae Sinensis 20-40 part Radix Paeoniae Rubra 20-40 part Radix Aucklandiae 20-30 part Radix Scutellariae 60-90 part

Rhizoma Corydalis 20-40 part

2, according to the described treatment anemofrigid-damp arthralgia of claim 1 and the muscles and bones soft medicine that withers, wherein each raw material optimum weight proportioning is:

45 parts of 30 parts of Radix Achyranthis Bidentataes of 30 portions of Rhizoma Et Radix Notopterygiis of 30 parts of Radix Angelicae Pubescentiss of 90 parts of Ramulus Cinnamomi of Caulis Sinomenii

6 parts in 30 parts of Cornu Cervi Pantotrichums of 30 portions of Radix Gentianae Macrophyllae of 30 parts of Radix Aconiti Lateralis Preparatas of 30 parts of Poria of Herba Taxilli

60 parts of 30 parts of Fructus Lycii of 30 parts of Radixs Astragali of 45 parts of Radix Codonopsis of 45 portions of Semen Coiciss of Radix Clematidis

90 parts of 24 parts of Radix Scutellariaes of 30 parts of Radix Aucklandiae of 30 parts of Radix Paeoniae Rubra of 30 parts of Radix Angelicae Sinensis of the Rhizoma Atractylodis Macrocephalae

30 parts of Rhizoma Corydalis

3, according to the described treatment anemofrigid-damp arthralgia of claim 1 and the muscles and bones soft medicine that withers, it is characterized in that said medicament is a said dosage form on any pharmaceutics.

4, according to the described treatment anemofrigid-damp arthralgia of claim 3 and the muscles and bones soft medicine that withers, it is characterized in that said medicament is tablet, capsule.

5, according to the described treatment anemofrigid-damp arthralgia of claim 1 and the muscles and bones soft medicine that withers, its preparation method is: Cornu Cervi Pantotrichum, Semen Coicis, Radix Aconiti Lateralis Preparata, Rhizoma Corydalis, Radix Codonopsis, Radix Paeoniae Rubra are ground into fine powder, Poria, the Radix Astragali, Fructus Lycii, Radix Achyranthis Bidentatae, Herba Taxilli, twice of water extraction of Radix Clematidis, the each extraction 1.5 hours, extract 98-102 ℃ of water temperature, extracting solution filters, and merging filtrate is evaporated to the thick paste of relative density 1.40-1.45 (60 ± 5 ℃ of heat are surveyed); The Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Radix Angelicae Pubescentis, Rhizoma Et Radix Notopterygii, Radix Gentianae Macrophyllae, Ramulus Cinnamomi, the Radix Aucklandiae, Radix Scutellariae, Caulis Sinomenii are with twice of ethanol extraction, the each extraction 1.5 hours extracted 78-82 ℃ of temperature, and extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.30-1.35 (60 ± 5 ℃ heat survey); Described fine powder above two kinds of thick pastes add, mixing is made bulky grain, vacuum drying, dry substance is ground into fine powder, and mixing is made said dosage form on any pharmaceutics.