CN102727750A

CN102727750A - Pharmaceutical composition for benefiting Yang and detoxifying and preparation method and application thereof

Info

Publication number: CN102727750A
Application number: CN2012102512147A
Authority: CN
Inventors: 张毅; 杨殿兴; 徐涛; 罗先本; 李希; 廖志航; 吴亚梅
Original assignee: Sichuan Academy of Chinese Medicine Sciences SACMS
Current assignee: Sichuan Academy of Chinese Medicine Sciences SACMS
Priority date: 2012-07-19
Filing date: 2012-07-19
Publication date: 2012-10-17
Anticipated expiration: 2032-07-19
Also published as: CN102727750B

Abstract

The invention discloses a pharmaceutical composition for benefiting Yang and detoxifying. The pharmaceutical composition is a preparation which is prepared by the following raw material drugs according to the weight ratios: 200-350 parts of scutellaria, 300-540 parts of sculellaria barbata, 200-350 parts of rhizoma pinellinae praeparata, 200-350 parts of epimedium, 200-350 parts of grifola, 400-700 parts of rhizoma polygonati, 400-700 parts of codonopsis pilosula, 200-350 parts of bupleurum, and 8-14 parts of cartialgenous. The invention also provides a preparation method and an application of the pharmaceutical composition. The pharmaceutical composition has anti-inflammatory, antipyretic and analgesic effects, and can enhance the immunity of the organism and physique, reduce the in-vivo HIV (human immunodeficiency virus) load of an HIV carrier, stabilize or increase the CD4 and T lymphocyte quantity of the HIV carrier, prolong or stabilize the AIDS (acquired immunodeficiency syndrome) asymptomatic period, and reduce the probability that the HIV carrier enters the period of morbidity of AIDS, thus being beneficial to the delay of onset process of a patient, improving the life quality of the patient, and providing a new choice for clinical medication.

Description

A kind of invigorating YANG antidotal pharmaceutical composition

Technical field

The present invention relates to a kind of invigorating YANG antidotal pharmaceutical composition.

Background technology

AIDS (acquired immunodecency syndrome, full name AIDS) is an AIDS, The World Health Organization (WHO) is according to CD4 ⁺The quantity of T lymphocyte (hereinafter to be referred as CD4) is divided into acute infection period, asymptomatic HIV infection period, AIDS stadium.This disease is by HIV (Human immunodeficiency virus, a kind of chronic lethal sexually transmitted disease that HIV) causes.HIV invades human immune system CD4 after infecting body specifically, CD4 quantity is reduced and function destruction; And then cause the immunity of organism balance to be broken; Cause immunologic function degression even depletion, and secondary body fluid regulatory function descends immunoglobulin content and abnormal proportion variation; Finally cause various opportunistic infection and tumor, and become the topmost cause of the death of AIDS.Find the first HIV sufferers so far from the U.S. in 1981, AIDS brings serious harm for human health and life at global rapid spread, has caused the attention of countries in the world at present.

The asymptomatic stage of AIDS is called asymptomatic HIV infection period, AIDS incubation period, generally no any symptom and sign except that lasting lymph nodes of body as a whole enlargement again.Previously doctor trained in Western medicine is to let alone Free Development for the processing method of this phase, perhaps only is to strengthen nutrition or exercise etc., does not take the medical intervention measure.In recent years; In order to protect the infected not and to avoid the propagation in the single positive family of HIV as far as possible; There are country and expert to advocate and as early as possible the infected carried out antiviral therapy (Antiretrovirus; But this scheme is also not long in the time that China uses, and also has the regular hour apart from people's desired destination ARV).The highly active antiretroviral therapy that we know (HAART) is though greatly reduce AIDS infections relating property disease incidence rate and mortality rate; But China only is used for CD4 HIV the infected less than 350/μ l at present, for most asymptomatic stage HIV the infected and inapplicable.In addition, than the toxic and side effects of higher medical expense, drug resistance, medicine and patient's compliance problem etc., restriction to a certain degree the clinical use of HARRT.Therefore, seek to tackle the effective means of AIDS asymptomatic stage, delay morbidity, perhaps become a breach that prevents and treats AIDS.

Though the asymptomatic stage of AIDS does not show specific symptom and sign, have in the immunopathogenesis that the T cell function is unusual, quantity reduces and the unusual immune activation state of body.At present, utilize Chinese medicine organic conception, strengthening vital QI to eliminate pathogenic factors idea and preventive treatment of disease thought that the human immune system is carried out many target spots, two-ways regulation, thereby delay morbidity, receive publicity just day by day aspect the AIDS preventing and treating.

Summary of the invention

The object of the present invention is to provide a kind of invigorating YANG antidotal pharmaceutical composition.

The invention provides a kind of invigorating YANG antidotal pharmaceutical composition, it is the preparation that is prepared from following materials of weight proportions medicine:

200 ~ 350 parts of Radix Scutellariaes, 300 ~ 540 parts of Herba Scutellariae Barbataes, 200 ~ 350 parts of Rhizoma Pinelliae Preparatum, 200 ~ 350 parts of Herba Epimedii, 200 ~ 350 parts of Polyporus, 400 ~ 700 parts of Rhizoma Polygonatis, 400 ~ 700 parts of Radix Codonopsis, 200 ~ 350 parts of Radix Bupleuri, 8 ~ 14 parts in Cornu Cervi Pantotrichum.

Further, it is the preparation that is prepared from following materials of weight proportions medicine:

250 ~ 300 parts of Radix Scutellariaes, 300 ~ 450 parts of Herba Scutellariae Barbataes, 250 ~ 300 parts of Rhizoma Pinelliae Preparatum, 250 ~ 300 parts of Herba Epimedii, 250 ~ 300 parts of Polyporus, 500 ~ 600 parts of Rhizoma Polygonatis, 500 ~ 600 parts of Radix Codonopsis, 250 ~ 300 parts of Radix Bupleuri, 10 ~ 12 parts in Cornu Cervi Pantotrichum.

Further preferably, it is the preparation that is prepared from following materials of weight proportions medicine:

278 parts of Radix Scutellariaes, 417 parts of Herba Scutellariae Barbataes, 278 parts of Rhizoma Pinelliae Preparatum, 278 parts of Herba Epimedii, 278 parts of Polyporus, 556 parts of Rhizoma Polygonatis, 556 parts of Radix Codonopsis, 278 parts of Radix Bupleuri, 11 parts in Cornu Cervi Pantotrichum.

Wherein, said pharmaceutical composition is to be active component by the water of said raw medicinal material fine powder or raw material or extractive with organic solvent, adds the preparation that adjuvant pharmaceutically commonly used is prepared from.

Further, said preparation is tablet, powder, capsule, granule, pill or oral liquid.

Further, in the said granule, contain baicalin 120 ~ 140mg in every 9g granule.

The present invention also provides the method for preparing of aforementioned pharmaceutical compositions, and it comprises following operating procedure:

(1) weighting raw materials by weight ratio;

(2) get the Rhizoma Pinelliae, Herba Scutellariae Barbatae adds 50 ~ 70%V/V alcohol reflux, filter, merging filtrate, filtrate recycling ethanol is not to there being the alcohol flavor, concentrated solution is subsequent use;

(3) get Radix Scutellariae, Radix Bupleuri, Polyporus, Rhizoma Polygonati, Radix Codonopsis, Herba Epimedii Six-element medical material, decocte with water, filtration, filtrating merges with the said concentrated solution of step (2), is concentrated into thick paste, and drying is pulverized, and it is subsequent use to get extract powder;

(4) get Cornu Cervi Pantotrichum, after the pulverizing, behind the said extract powder mixing of step (3), add appropriate amount of auxiliary materials, be prepared into preparation pharmaceutically commonly used.

Further, the concrete operations of step (2) are: get the Rhizoma Pinelliae, Herba Scutellariae Barbatae adds alcohol reflux 3 times, first and second time adds 10 times of amount 50% ethanol; Add 70% alcohol reflux for the third time, each 1 hour, filter; Merging filtrate, filtrate recycling ethanol is not to there being the alcohol flavor, and concentrated solution is subsequent use;

The concrete operations of step (3) are: get Radix Scutellariae, Radix Bupleuri, Polyporus, Rhizoma Polygonati, Radix Codonopsis, Herba Epimedii Six-element medical material, add 12 times of amounts of water and decoct twice, each 1.5 hours; Filter; Filtrating merges with the said concentrated solution of step (2), the thick paste of reconcentration to 60 ℃ survey relative density 1.30, drying; Pulverize, it is subsequent use to get extract powder;

In the step (4), Cornu Cervi Pantotrichum adopts the micronizing method to pulverize.The micronizing method is meant that utilizing machinery or hydrokinetic method to overcome the solid interior cohesiveness makes it broken, thereby the material particles more than 3 millimeters is crushed to the operating technology of 10-25 micron.

The present invention also provides the above-mentioned purposes of pharmaceutical composition in the medicine of preparation treatment AIDS.

Further, said medicine is stable or the medicine of treatment AIDS asymptomatic stage.

Further, said medicine is anti HIV-1 virus, stable or rising AIDS virus carrier CD4 ⁺The medicine of T lymphocyte quantity.

Invade human body from HIV, through window phase and asymptomatic stage, preceding this section process occurs to the AIDS syndrome and be called AIDS viral infection (HIV infection), infected person is AIDS virus carrier (HIV carriers) or the infected.

The present invention also provides above-mentioned pharmaceutical composition preparing enhance immunity, antiinflammatory, analgesic or/and the purposes in the medicine of analgesic.

In the pharmaceutical composition of the present invention, Radix Scutellariae and Herba Scutellariae Barbatae are share, and are monarch drug altogether.Radix Scutellariae nature and flavor bitter cold is returned lung, gallbladder, spleen, intestine and small intestine warp, and effect is a heat clearing and damp drying, eliminating fire and detoxication.Can treat malignant boil, cellulitis erosion, acute scleritis.Herba Scutellariae Barbatae is arduous cold, but heat-clearing and toxic substances removing, the dissipating blood stasis diuresis.Two medicines all can dampness detoxify, and in we, play eliminating evil main effect, make " heresy is gone to then Zhengan County ".Radix Codonopsis, Rhizoma Polygonati, Cornu Cervi Pantotrichum, Herba Epimedii share and are ministerial drug.Radix Codonopsis property is flat, sweet in the mouth, little acid.Return spleen, lung meridian, effect is invigorating middle warmer, and QI invigorating promotes the production of body fluid." Bencao Congxin " carries: (Radix Codonopsis) invigorating the spleen and replenishing QI and taste relieving thirst and restlessness; The Rhizoma Polygonati nature and flavor are sweet flat, go into three yin meridians, but the nourishing kidney lung moistening, invigorating the spleen and replenishing QI.Two medicines share, reinforce spleen and kidney together, and spleen invigorating is with QI invigorating, and the kidney invigorating reaches the effect of supplementing QI and nourishing YIN jointly with yin nourishing.Cornu Cervi Pantotrichum share Herba Epimedii and consolidates with warming YANG, and wherein Cornu Cervi Pantotrichum is the in love article of flesh and blood, and is warm in nature fostering the spirit of nobility, rich can benefit smart.Have invigorating kidney-YANG, mend marrow, bone and muscle strengthening is transferred to dash and is appointed, the effect of holder sore.Compendium of Material Medica is carried: " (Cornu Cervi Pantotrichum) spermatogenesis is mended marrow, the Yiyang of nourishing blood, strong muscles and bones.Control that all are deficient, deafness, order is dark, and is dizzy, dysentery of deficiency type." Cornu Cervi Pantotrichum is the tender angle of stag, includes the gas of few positive hair growth promoting, measure little and imitate tall and erect, the meaning of residence junior fire supporting vital QI, yang-energy is sufficient, spirit is prosperous.Herba Epimedii acrid in the mouth warm in nature, but kidney-replenishing, bone and muscle strengthening, wind-damp dispelling." herbal classic " cloud: " (Herba Epimedii) main impotence is hindered pains in the penis extremely.Diuresis, physical strength profiting, strong will." two medicines share, but warming the kidney to activate YANG, the benefit essence is added marrow, and kidney yang is sufficient, and QI and blood is spontaneous so the whole body yang-energy is prosperous, and it is full and biochemical active that essence is filled marrow.In addition, two medicines also have the wonderful of negative and positive alternate with Rhizoma Polygonati.Zhang Jingyue is said: " kind YANG invigorating person must be in treating YANG within YIN, then positive cloudy helping and biochemical infinite ".This side also can help cloudy gas with treating YANG within YIN with Rhizoma Polygonati, and negative and positive are changed and biochemical without cease mutually.Polyporus, Radix Bupleuri, the Rhizoma Pinelliae are adjuvant drug.Polyporus " herbal classic " is carried it: " abnormal smells from the patient is sweet flat, nontoxic.Cure mainly malaria, the detoxifcation a disease similar to tuberculous or complicated with pulmonary tuberculosis is ominous, dredging water passages.Clothes are made light of one's life by commiting suicide anti-old for a long time." both permeable dampness removing, can detoxify again.Damp being a kind of YIN pathogen, water is wet, and to remove then spleen soil strong and QI and blood biochemistry is active, haze disappear and the yang-energy beginning prosperous.Be intended to help monarch drug to strengthen the effect of detoxifcation removing dampness with this medicine.Radix Bupleuri property bitterness is slightly cold, and returns the liver and gall warp." herbal classic " carries: (treatment) cold and heat pathogen pushes away Chen Zhixin.Share with Radix Scutellariae, the Rhizoma Pinelliae, but treating SHAO YANG disease by mediation, strengthening vital QI to eliminate pathogenic factors.Few sun be the warp of half exterior and half interior, and positive deficiency is pathogen invading YANG MING then, and the healthy energy abundance is then evil sunny, just with little Radix Bupleuri this meaning just, makes few positive important department tonneau, and pathogen must not be along through interior biography.All medicines share, reinforcement and elimination in combination, and it is main detoxifying eliminating evil, and strengthening the body resistance is auxilliary, and eliminating evil just the wound sets upright and do not hold back heresy, plays the merit of invigorating YANG detoxifcation altogether.

Pharmaceutical composition of the present invention can enhancing human body immunity and body constitution, has antiinflammatory, analgesic, analgesic activity, can reduce HIV virus load in HIV carriers' body, and is stable or increase HIV carriers CD4 ⁺The T lymphocyte quantity prolongs or stable AIDS asymptomatic stage, reduces HIV carriers and gets into the probability of AIDS period of disease, helps delaying patient's morbidity process, has improved patient's quality of the life, for clinical application provides a kind of new selection.

Description of drawings

Fig. 1 HIV virus changes broken line graph in time;

Fig. 2 CD4 counting changes broken line graph in time.

The specific embodiment

Embodiment 1 preparation of drug combination method of the present invention

Prescription:

Radix Scutellariae 278g Herba Scutellariae Barbatae 417g Rhizoma Pinelliae Preparatum 278g Polyporus 278g

Radix Bupleuri 278g Rhizoma Polygonati 556g Radix Codonopsis 556g Herba Epimedii 278g

Cornu Cervi Pantotrichum 11g

Method for making:

More than nine the flavor medical materials, the Cornu Cervi Pantotrichum micronizing, subsequent use; Rhizoma Pinelliae Preparatum, Herba Scutellariae Barbatae add alcohol reflux three times, and first and second time adds 10 times of amount 50% ethanol, adds 70% alcohol reflux for the third time, and each 1 hour, filter, merging filtrate, filtrate recycling ethanol is to there not being the alcohol flavor, and is subsequent use; Radix Scutellariae, Radix Bupleuri, Polyporus, Rhizoma Polygonati, Radix Codonopsis, Herba Epimedii Six-element medical material add 12 times of amounts of water and decoct twice, each 1.5 hours, filter; Filtrate and above-mentioned combining medicine, be concentrated into the thick paste of relative density 1.30 (60 ℃), drying is pulverized; Add Pulveratum Cornu Cervi Pantotrichum, an amount of dextrin, mixing is processed granule 1000g; Drying, granulate promptly gets.

Embodiment 2 preparation technologies' screening study

1, extraction process technology Study on Conditions

(1) research of disintegrating process:

According to these article prescription drugs wood property matter result of study, the Cornu Cervi Pantotrichum medical material is beaten powder, micronizing, it is received powder rate investigation result and sees table 1.

Table 1 Cornu Cervi Pantotrichum is beaten the powder yield and is investigated the result

The above results shows: the Cornu Cervi Pantotrichum medical material is beaten powder, and receiving the powder rate is 97.10%.

(2) research of alcohol extraction process

1. the investigation of water absorption rate

Vegetable drug all has the ability of absorption solvent in various degree, and the big young pathbreaker of lyosoption amount influences the effect of extraction.Therefore, carry out the investigation of water absorption rate.

Take by weighing Herba Scutellariae Barbatae, Rhizoma Pinelliae Preparatum two flavor medical materials 50g altogether in the prescription ratio, add 70% ethanol 1000ml and soak.The every observation at a distance from half an hour once soaked into the mood condition, and medical material all soaks into after 3 hours, filters, and measures unabsorbed liquid, and volume is 933ml; Then water absorption rate is:

（1000－933）/50×100%=134%

So confirm when adding ethanol extraction for the first time, to supply medical material water absorption (add during decocte with water for the first time and add) into 1.34 times of amount ethanol.

2. Orthogonal Experiment and Design

Alcohol adding amount, extraction time, extraction time, solvent strength are the key factors that influences alcohol extraction process.In order to screen the extraction process condition, each factor has designed three levels, presses L ₉(3 ⁴) carrying out orthogonal test, table 2 is seen in the gauge outfit design.

Factor-the water-glass of table 2 alcohol extraction process

Test method

In the prescription ratio take by weighing Herba Scutellariae Barbatae 30g, Rhizoma Pinelliae Preparatum 20g amounts to 50g, carries out ethanol extraction when adding ethanol (for the first time, add by the medical material water absorption rate) by the orthogonal test condition of design, medicinal liquid filters with 200 order filter clothes, filtrates concentrated and is settled to relative quantity.

3. index and assay method

Evaluation index

These article are alcohol extraction process; Composition and dosage form requirement according to prescription drug; Consider that main effective ingredient all is soluble in ethanol, and most of water soluble ingredient is that impurity is prone to remove, dried simultaneously cream yield is as the reference index of selecting dosage form; Influence the selection of impurity-removing method, be granule day dosing, single dosing and the important parameter confirmed of packing specification so select for use dried cream yield as evaluation index.

Dried cream yield

Accurate each the sample liquid 20ml of quadrature that draws places the evaporating dish (establishing weight is M) that has been dried to constant weight respectively, and water-bath volatilizes, and residue takes out in 105 ℃ of dryings 3 hours, places exsiccator to place half an hour, and weigh (establishing weight is N) calculates.

Annotate: V is each sample liquid constant volume of orthogonal test.

Carry out orthogonal test with condition as stated above, the result is following:

The orthogonal test table of table 3 alcohol extraction process condition

Table 4 alcohol extraction process orthogonal test analysis of variance table

F _0.05(2,2)=19 F _0.01(2,2)=99 ^*P<0.05, have the significance difference.

Can know that by intuitive analysis the factor that influences extraction effect is in proper order: C>A>B>D.Through variance analysis, extraction time has appreciable impact to extraction effect, and optimum extraction process is: A ₂B ₂C ₃D ₁, optimised process is for adding 10 times of medical material amounts, 50% alcohol reflux three times, each 1 hour; But the contained scutellarin of Herba Scutellariae Barbatae also is one of active ingredient in the side of considering, and hopes to preserve as much as possible, consults a large amount of documents and materials; The optimum extraction condition of scutellarin is 70% ethanol, so adjust alcohol extraction process for adding 10 times of medical material amount alcohol reflux three times, first and second time adds 10 times of amount 50% ethanol; Add 70% alcohol reflux for the third time, each 1 hour, promptly get.

Demonstration test

In order to verify the accuracy of The above results, to guarantee the rationally feasible of extraction process,, arrange repeated trials by above-mentioned definite process conditions, result of the test is seen table 5.

Table 5 quadrature demonstration test result

6-6 is visible from table: the basically identical as a result of three demonstration tests, explain that the technology that is screened closes

Manage feasiblely, reliable and stable, have operability and repeatability.

(3) research of extraction process by water

1. the investigation of water absorption rate

Take by weighing Radix Scutellariae, Herba Epimedii, Rhizoma Polygonati, Radix Codonopsis, Radix Bupleuri, Polyporus Six-element medical material 170g altogether in the prescription ratio, add water 1000ml and soak.The every observation at a distance from half an hour once soaked into the mood condition, and medical material all soaks into after 3 hours, filters, and measures unabsorbed water liquid, and volume is 763ml; Then water absorption rate is:

（1000－763）/170×100%=139%

So confirm when first time decocte with water, to supply medical material water absorption (adding is added into 1.5 times of water gagings during decocte with water for the first time).

2. Orthogonal Experiment and Design

Amount of water, decocting time, decoction number of times are the key factors that influences decocting technology.In order to screen the extraction process condition, each factor has designed three levels, presses L ₉(3 ⁴) carrying out orthogonal test, table 6 is seen in the gauge outfit design.

Table 6 decocting process factors-water-glass

Test method

Take by weighing Radix Scutellariae 20g, Radix Bupleuri 20g, Polyporus 20g, Rhizoma Polygonati 40g, Radix Codonopsis 40g, Herba Epimedii 20g in the prescription ratio; The Six-element medical material is 170g altogether; Carrying out water by the orthogonal test condition of design carries (when adding water for the first time; Add by the medical material water absorption rate), medicinal liquid filters with 400 order filter clothes, and filtrating concentrates and is settled to relative quantity.

3. index and assay method

Evaluation index

Extraction process by water, according to the composition and the dosage form requirement of prescription drug, selecting dried cream yield and content of baicalin for use is evaluation index, carries out overall merit.Dried cream yield influence the selection of impurity-removing method as the reference index of selecting dosage form, is granule day dosing, single dosing and the definite important parameter of packing specification.Therefore with dried cream yield as one of evaluation index, but it does not become dose-effect relationship with curative effect intensity, so weight coefficient should be less during overall merit, is advisable with 0.2.Monarch drug in the Radix Scutellariae side of being, and tangible Detoxication is arranged, therefore select for use the high performance liquid chromatogram algoscopy to measure content of baicalin in the Radix Scutellariae, also as one of evaluation index, and weight coefficient should be relatively large, is advisable with 0.8.

Dried cream yield

Annotate: V is each sample liquid constant volume of orthogonal test.

Content of baicalin is measured

● the selection of maximum absorption wavelength:

Scanning: reference substance solution is done blank with methanol, scan at 200 ~ 600nm place.

The result: reference substance solution has absorption maximum at the 280nm place; In conjunction with " therefore one one 211 pages radix scutellariae medicinal materials assay conditions of Chinese pharmacopoeia version in 2005, select need testing solution to measure wherein content of baicalin at the 280nm place.

● chromatographic condition and system suitability test

Use octadecylsilane chemically bonded silica to be filler, methanol-water-phosphoric acid (47:53:0.2) is a mobile phase; The detection wavelength is 280nm; 30 ℃ of column temperatures; Flow velocity is 1ml/min.Number of theoretical plate calculates by baicalin should be not less than 2500.

● the preparation of reference substance solution

Precision takes by weighing 60.4 hours baicalin reference substance of C drying under reduced pressure is an amount of, puts in the 50ml volumetric flask, adds dissolve with methanol and is settled to scale, processes the solution that every 1ml contains baicalin 123 μ g, promptly gets.

● the preparation of need testing solution

9 orthogonal test medicinal liquids of accurate absorption dilute corresponding multiple respectively, filter, and filter with the 0.45um microporous filter membrane, promptly get.

● algoscopy

Precision is measured baicalin reference substance solution (123.8ug/ml), respectively with 2.0,4.0,6.0; 8.0,10.0 μ l sample introductions, record chromatogram; Measure peak area value, and be vertical coordinate with peak area value A, sample size C (μ g) is an abscissa; Make a straight line respectively, get regression equation: A=2804.19C-56.655r=0.99995, measure the result and see table 7.

The table 7 baicalin reference substance range of linearity is measured the result

The orthogonal test table of table 8 extraction process by water condition

Table 9 extraction process by water orthogonal test analysis of variance table

F _0.05(2,2)=19 F _0.01(2,2)=99 ^*P<0.05, have the significance difference.

Can know that by intuitive analysis the factor that influences extraction effect is in proper order: C>B>A>D.Through variance analysis, decocting time, decoction number of times have appreciable impact to extraction effect, and optimum extraction process is: C ₃B ₂A ₂, optimised process is A ₂B ₂C ₃, promptly add the water of 12 times of medical material amounts, decoct each 1.5 hours 2 times.

Demonstration test

In order to verify the accuracy of The above results, to guarantee the rationally feasible of extraction process,, arrange repeated trials by above-mentioned definite process conditions, result of the test is seen table 10.

Table 10 quadrature demonstration test result

6-11 is visible from table: the basically identical as a result of three demonstration tests, explain that the technology that is screened is rationally feasible, and reliable and stable, have operability and repeatability.

6.4.3 isolation and purification technical study

These article are solid preparation; The requirement of no clarity, medicinal liquid only need be removed solid particle and macromolecular substances, extract part since in the medicinal liquid contained macromole impurity and solid particle less; Therefore medicinal liquid only needs to filter with 400 order nylon filter clothes, and merging filtrate concentrates.

6.4.4 concentrate and drying process research

(1) concentration technology research

For preventing that effective ingredient receives heat damage for a long time; Adopt the most frequently used sophisticated equipment in present pharmaceutical factory; Be that pressure regulating equipment carries out ethanol recovery and concentrated, its actual conditions is: temperature is 70 ℃, and vacuum is 0.08～0.1Mpa; Be concentrated into the thick paste that relative density of medicine liquid is about 1.30 (60 ℃), subsequent use.

(2) research of drying process

After extractum took out, 80 ℃ of dryings were pulverized 60 mesh sieves, and were subsequent use.

6.4.5 preparations shaping research

1. preparation prescription design

(1) selection of hygroscopic agent kind and consumption

Because the dried cream hygroscopicity of these article is stronger, thus select a certain amount of hygroscopic agent as adjuvant, and be index with the hydroscopicity, the kind and the consumption of hygroscopic agent have been done single factor investigation.

The hydroscopicity assay method: the glass exsiccator that the bottom is placed with the NaCl supersaturated solution is put into baking oven; In 40 ℃ of heating 5h; Making the interior humidity relatively of exsiccator is 75.3%, in the constant weight weighing botle, puts into the thick medicated powder of 3mm, puts into exsiccator (opening the weighing bottle cap) after precision is weighed; Take out precision after regularly (72h) covers the weighing botle bottle cap completely and weigh, calculate its moisture absorption percentage rate.The result sees the following form.

The selection of table 11 hygroscopic agent kind

Can know that by table hydroscopicity is lower behind the adding dextrin, so the selection dextrin is a hygroscopic agent.

(2) mensuration of powder flowbility

The assay method of angle of repose: generally be to make micropowder or granule flow down and become the cone heap through a funnel.If the cone height is H, the cone base radius is R, tan α=H/R then, and α is angle of repose.Adopted fixedly circular cone channel process in the mensuration: by at the bottom of the round box of fixed size or lid accept the micropowder that leaks down by funnel, constantly inject micropowder in the funnel, till obtaining the highest cone, calculate angle of repose.Get dry gained fine powder, adopt fixedly conical bottom method, measuring angle of repose is 38.8 ° (n=3), shows that its powder flowbility is better, is convenient to packing.

(3) mensuration of bulk density

Bulk density is meant unit volume micropowder or particulate quality.Assay method: take by weighing the about 3g of the medicated powder that adds adjuvant, in the 10ml graduated cylinder of packing into, fall for several times (each guarantee test term harmonization), make degree of tightness suitable, with weight and its value of volume calculations with level altitude.

Table 12 medicated powder bulk density is measured the result

Result of the test shows that the average bulk density of medicated powder is 0.668g/ml.

(3) preparation prescription confirms

It is 52.7g that we take the crude drug amount every day, wherein beats powder part medical material fine powder 0.2g, and the about 15.39g of paste volume after the medicinal material extract, remove impurity, medical material micropowder 0.2g, dextrin 2.41g, about 18g altogether.By taking every day 2 times, take 9g at every turn; Be equivalent to take every day the 52.7g crude drug in whole, can reach clinical needs.Because of obeying crude drug in whole 52.7g clinical every day, be equivalent to these article medicated powder 18g, so every bag of granule dress of regulation 9g at every turn.According to aforementioned calculation, preparation prescription is:

2. half-finished quality control

For guaranteeing the concordance and the stability of end product quality, prepare in the process at said preparation, must carry out quality control to semi-finished product, measured particulate angle of repose, bulk density, critical relative humidity for this reason.

(1) angle of repose

Be one of method for expressing of mobility of particle angle of repose.Its assay method generally is to make granule flow down and become cone heap through a funnel.If the cone height is H, the cone base radius is R, tan α=H/R then, and α is angle of repose.Adopted fixedly circular cone channel process in the mensuration: by at the bottom of the round box of fixed size or lid accept the granule that leaks down by funnel, constantly inject granule in the funnel, till obtaining the highest cone, calculate angle of repose.

Table 13 granule is measured the result angle of repose

Result of the test shows, this granule is better mobile less than 40 ° angle of repose, is easy to packing.

(2) research of granule hygroscopic nature

1. the mensuration of moisture equilibrium at dry side time:

Get the glass exsiccator that the bottom fills the NaCl supersaturated solution, the built-in weighing botle of exsiccator was put into 25 ℃ of thermostatic drying chamber constant temperature 24 hours, and the interior relative humidity of exsiccator this moment is 75%.Get 8 duplicate samples, the about 2g of every duplicate samples puts in the weighing botle, accurate claims surely, will claim that ware covers to open, and puts into exsiccator top, in 25 ℃ of thermostatic drying chambers, preserves, and takes out 1 duplicate samples at regular intervals and weighs once, calculates the moisture absorption percentage rate of each time.Result of the test is seen table 14.

Table 14 moisture absorption percentage rate is measured table as a result

Visible by granule moisture equilibrium at dry side curve, basically no longer moisture absorption behind these article granule 120 hours (5 days), the moisture absorption percentage rate thinks that 9.96% these article have certain moisture property.

2. critical relative humidity:

Moisture is very big to the influence of solid preparation stability, and moisture absorption is the recurrent phenomenon of solid preparation of Chinese medicine, causes the precondition of other variations often.And ambient humidity is maximum to the influence that hygroscopic effect takes place in preparation, branch process of assembling granule.Therefore,, measured particulate critical relative humidity, made these article moisture equilibrium at dry side curve, for the relative humidity of controlling the packing workshop provides reference frame for preventing the granule moisture absorption.Assay method: get 7 parts of granules, every part of about 2g places the open weighing botle of claiming weight and numbering, and accurate the title decides; Open the weighing bottle cap, put into the glass exsiccator middle level of different humidity respectively,, take out tared dish in 25 ℃ of condition held 120 hours; It is fixed to add a cover the accurate title in back, and the hygroscopic capacity of calculation sample is an abscissa with the relative humidity; Hygroscopic capacity is a vertical coordinate, draws sucting wet curve, and the result sees table 15.

Table 15 moisture equilibrium at dry side amount result of the test table

By on can find out, obviously strengthen in 62% above moisture absorption.Therefore, the critical relative humidity that can confirm finished product is 62%.In packing, storage process, ambient humidity must be controlled at below 62%.The selection of 3 packaging material

According to the wettability test result of study, these article hygroscopicity is stronger, so select good sealing performance aluminum

The plastic packaging dress can satisfy packing instructions.

4 packing

By pack into the plastic-aluminum encapsulation of the specification of every bag of 9g, the dress box promptly gets with granule.

Below through Test Example beneficial effect of the present invention is described.

Test Example 1 pharmaceutical composition of the present invention is to HIV the infected's influence

1 research purpose

Observe pharmaceutical composition of the present invention (embodiment 1 preparation is to call the invigorating YANG detoxification particles in the following text) and, its clinical efficacy is made evaluation the antiviral and the immunological enhancement of HIV the infected's asymptomatic stage.

2 object of study

2.1 case source

This research case is Chengdu, Sichuan Province, Xichang City and Butuo County and infects the asymptomatic stage patient by the HIV that CDC confirms, amounts to 72 examples.

2.2 diagnostic criteria

Can be referring to CDC. AIDS clinical treatment and nursing training materials [M] (front page). Beijing: BJ University Press, 2003:194-196.

2.2.1 epidemiological history

The insecurity life cycle;

The intravenous injection drug use history;

Input is without the blood and the blood products history of anti-HIV antibody test;

HIV antibody positive children that the person gives birth to;

Other (occupational exposure or nosocomial infection histories).

2.2.2 clinical manifestation

General no any clinical manifestation, but visible lymph nodes of body as a whole enlargement.

2.2.3 lab testing

The HIV antibody positive is through the validation test prover;

HIV-RNA is positive in patient's blood plasma.

2.2.4 the standard of making a definite diagnosis

The patient has among the 2.2.1 among any one and the 2.2.3 any one and have the phenomenon among the 2.2.2 to make a definite diagnosis.

2.2.5 standard by stages

2.2.5.1 acute infection period

Patient has epidemiological history and clinical manifestation at no distant date, and it is promptly diagnosable to change sun in conjunction with laboratory HIV antibody, or only lab testing HIV antibody positive is promptly diagnosable.

2.2.5.2 asymptomatic stage

Epidemiological history is arranged, promptly diagnosable in conjunction with the HIV antibody positive, or only lab testing HIV antibody positive is promptly diagnosable.

2.2.5.3 AIDS stadium

Lab testing HIV antibody positive and CD4 200/μ l is promptly diagnosable, or lab testing HIV antibody positive below adding any one also diagnosablely be AIDS.

Agnogenic lasting irregular heating is more than 38 ℃, above 1 month;

The chronic diarrhea number of times is greater than 3 times/day, above 1 month;

Lose weight more than 10% in 6 months;

The oral Candida albicans of outbreak infects repeatedly;

The Pneumocystis pneumonia appears;

The bacterial pneumonia that takes place repeatedly;

Active tuberculosis or non-tuberculous mycobacteria infect;

The herpes simplex of outbreak or varicella zoster virus infect repeatedly;

Deep fungal infection;

Central nervous system's occupying lesion, or occur dull-witted;

The toxoplasma encephalopathy;

The septicemia of showing effect repeatedly;

Penicillium infects;

The Kaposi's sarcoma of skin mucosa or internal organs, lymphoma;

Crypotococcal or cryptococcus pneumonia;

The activeness cytomegalovirus infection.

2.3 the standard of including in

The patient who meets the diagnostic criteria of AIDS asymptomatic stage Chinese and western medicine is ready partner treatment, regularly further consultation on schedule, and compliance is good, knows the inside story and signature Informed Consent Form person.Virus load more than 100,000 copy/ml, CD4 is lower than HIV the infected of 350/ul, western medical treatment is carried out in suggestion.

2.4 get rid of the case standard

Age of sucking, trimester of pregnancy or the women who prepares gestation.

Cardiovascular and cerebrovascular disease, hepatorenal damage and disease of hematopoietic system person are arranged.

To this experiment medicine allergy sufferers and the person that is unwilling to use the Chinese medicine.

2.5 abort criterion

In the drug administration process, the person that the serious adverse reaction occurs.

In the project implementation process, find the Chinese medicine deviation, be difficult to assess medicinal effectiveness person.

The Sichuan Province State Administration of Traditional Chinese Medicines or food control office order termination person because of certain reason.

2.6 reject the case standard

Do not meet the standard of including in and the quilt person of including in.

Though meet the standard of including in, after including in not by stipulating the pill taker.

Compliance is bad, not further consultation on time, or add Chinese and western drugs person voluntarily with the other treatment primary disease.

3 research approaches

3.1 nomenclature of drug, composition and specification

Invigorating YANG detoxification particles (lot number 20100302), prescription comprises that Radix Scutellariae, Herba Scutellariae Barbatae, Rhizoma Pinelliae Preparatum, Polyporus, Radix Bupleuri, Rhizoma Polygonati, Radix Codonopsis, Herba Epimedii, Cornu Cervi Pantotrichum, adjuvant are dextrin.Have warming YANG and consolidate, supplementing QI and nourishing YIN, detoxifcation removing dampness effect.Every bag of 9g, 10 bags of every bags.

3.2 method of administration

Sooner or later half an hour, warm water took after meal, and each 1 bag, 2 times on the one.

3.3 clinical indexes

The further consultation in January is once observed 1 year (2011.3-2012.3) altogether, collects the 3rd, 6,9, the CD4 and the virus load value of December.

3.4 curative effect determinate standard

According to " the Chinese medicine AIDS clinical technology scheme " of Sichuan Province State Administration of Traditional Chinese Medicines promulgation in 2004, this research is mainly from immunologic function and virus load two aspect evaluations.

3.4.1 immunologic function

Effectively: cd4 cell rises gradually, cd4 cell rising >=30% of treatment back or 50/ul;

Stable: cd4 cell no change or rising gradually, treatment back cd4 cell raises or decline＜30% or 50/ul;

Invalid: cd4 cell decline >=30% or 50/ul.

3.4.2HIV virus load

Effectively: blood plasma HIV virus load descends, copy number reduction >=0.5lg/ml;

Stable: blood plasma HIV virus load rises or decline＜0.5lg/ml;

Invalid: blood plasma HIV virus load continues to rise copy number >=0.5lg/ml.

3.5 adverse events is observed

3.5.1 adverse events record

Period in a medicine is recorded faithfully time of origin, persistent period, the order of severity and the effective measures of taking of adverse events and is lapsed to.

3.5.2 adverse events extent of disease severity

Slightly: slight uncomfortable, the experimenter can stand, and does not influence treatment, does not need special handling, and experimenter's treatment and rehabilitation are not had influence.

Moderate: moderate is uncomfortable, and the experimenter is difficult to stand, and needs special handling, and experimenter's rehabilitation is had direct influence.

Severe: severe is uncomfortable, jeopardizes experimenter's life, causes death or disables, and need do emergent management immediately.

3.5.3 the processing of adverse events

If any serious adverse events takes place in process of the test; All medicines that must stop using used immediately also report this city (state) health bureau and Sichuan Province this project office of the State Administration of Traditional Chinese Medicines; Fill in " serious adverse events account "; And the requirement of serious adverse effect incident takes place according to medical institutions, report corresponding administration section.

3.5.4 adverse events is followed up a case by regular visits to

After the patient adverse events occurs and handles January, should follow up a case by regular visits to, to guarantee patient safety.

3.6 safety evaluatio

Owing to receive the restriction of experiment condition and funds, whole patients do not carried out inspections such as routine blood test, Liver and kidney merit, routine urinalysis, electrocardiogram and rabat, so can't make safety evaluatio.

3.7 ethics

All patients that participate in this research all sign Informed Consent Form, can freely obtain CD4 detection and virus load detection at viewing duration, and have the clinician to help to solve the discomfort that occurs in the research process.

3.8 statistical method

Adopt the SPSS19.0 software kit to carry out statistical analysis; All data all adopt mean ± standard deviation

expression, and measurement data compares with pairing T check; With P>0.5 be the difference not statistically significant, < 0.5 has statistical significance for difference to P.

4 results of study

4.1 case situation

Among the 72 routine patients, male's 43 examples, women's 29 examples, minimum 21 years old of age, maximum 68 years old, 30.25 ± 1.73 years old mean age.

The infected's PI time 2-8, average 2.54 ± 1.36 years.

72 routine patients all are asymptomatic HIV infection period patient.

Reject 2 examples in the research process, 6 examples come off.

4.2 efficacy analysis

4.2.1 CD4 relatively before and after the treatment

Compare (

is individual/μ l) n=47 with treatment CD4 value at 3 the end of month before table 16 treatment

Through T check, P>0.05, the difference not statistically significant.

Compare ( is individual/μ l) n=37 with treatment CD4 value at 6 the end of month before table 17 treatment

Through T check, P>0.05, the difference not statistically significant.

Compare (

is individual/μ l) n=22 with treatment CD4 value at 9 the end of month before table 18 treatment

Through T check, P>0.05, the difference not statistically significant.

Compare (

is individual/μ l) n=14 with treatment CD4 value at 12 the end of month before table 19 treatment

Through T check, P>0.05, the difference not statistically significant.

4.2.2 the CD4 curative effect relatively before and after the treatment

CD4 situation of change before and after table 20 treatment

4.2.3 virus load relatively before and after the treatment

Compare (

log/ml) n=64 with treatment virus load at 3 the end of month before table 21 treatment

Through the T check, < 0.05, difference has statistical significance to p.

Compare (

log/ml) n=49 with treatment virus load at 6 the end of month before table 22 treatment

Through the T check, < 0.05, difference has statistical significance to p.

Compare (

log/ml) n=39 with treatment virus load at 9 the end of month before table 23 treatment

Through the T check, < 0.05, difference has statistical significance to p.

Compare (

log/ml) n=29 with treatment virus load at 12 the end of month before table 24 treatment

Through the T check, < 0.05, difference has statistical significance to p.

4.2.4 the virus load curative effect relatively before and after the treatment

Virus load situation of change before and after table 25 treatment

Table 26 is selected in, rejects and the case situation that comes off

4.2.5 virus load mean broken line graph (see figure 1)

4.2.6CD4 mean broken line graph (see figure 2)

5 efficacy result analyses

To the lymphocytic influence of CD4+T: 3,6,9, December patient CD4 and 0 month relatively, equal no difference of science of statistics (P>0.05).Foreign data shows that therapist CD4+T cell fall off rate is not approximately annual 50/mm ³(Deng Xin. AIDS Chinese and Western combines clinical treatment [M]. Shanghai: publishing house of The 2nd Army Medical College, 2010:68), explain that the invigorating YANG detoxification particles has certain effect to the CD4 that stablizes asymptomatic stage HIV the infected; Treatment 3,6,9,12 inefficiencies are respectively 40.4%, 24.2%, 27.7%, 14.3%, can find out that along with the prolongation of treatment time, inefficiency totally is reduction trend, explain that invigorating YANG detoxification particles effect on late result is preferable.

Influence to the infected HIV virus load: the virus load effective percentage that the invigorating YANG detoxification particles reduces asymptomatic stage HIV the infected reaches 62.1%; Coefficient of stabilization reaches 20.7%; Explain that we are better to reducing asymptomatic stage HIV the infected virus load curative effect, can reduce or stablize asymptomatic HIV infection period person's virus load.Treated for 3 the end of month under the situation of larger samples, effective percentage is 68.8%, coefficient of stabilization 23.4%.The virus load that invigorating YANG detoxification particles reduction HIV infection asymptomatic stage patient is described also is effective in a short time.Through to treat 3,6,9, the analysis of December virus load; Comparing difference all has statistical significance (P < 0.05) before finding 3,6,9,12 the end of month of treatment and treating; Explain that the invigorating YANG detoxification particles has the effect of confirming to reducing asymptomatic stage HIV the infected virus load, has good inhibition effect to HIV virus.

6 model cases

Case 1: Luo, the man is 34 years old, more than the schooling junior college, unmarried.First visit on March 11 in 2011.Main suit: find HIV and infect the 5+ month.Medical history situation: except that the cervical lymph node enlargement, do not have other symptoms.The patient previously has the heart disease medical history, and the route of transmission is that the opposite sex spreads through sex intercourse, and approximately infection time is 2 years, no vein bang history.Have a medical check-up: vital sign is normal, body weight 55kg, and the cervical lymph node palpation is about about 1cm, slight oral ulcer.Red tongue with thin fur is white, rolling pulse.Auxiliary examination: virus load:>10 ⁵Copy/ml, CD4 492cell/ μ l, WBC 5.0 * 10 ⁹/ L, LYM 2.4 * 10 ⁹/ L, HGB156g/L, CR 91.6mol/L, BUN 6.6mmol/L, ALT 32IU/L, AST 30IU/L.Be diagnosed as HIV and infect asymptomatic stage, noxious dampness retardance card.Give the invigorating YANG detoxification particles, half an hour, warm water took after meal, and each 1 bag, 2 times on the one.

Any discomfort is not told in further consultation on June 11 in 2011.Have a medical check-up: vital sign is normal, body weight 57kg, and the cervical lymph node palpation is about about 1cm, and red tongue with thin fur is white, rolling pulse.Auxiliary examination: virus load: 10 ⁵Copy/ml, CD4 549cell/ μ l, WBC 4.6 * 10 ⁹/ L, LYM 2.1 * 10 ⁹/ L, HGB 160g/L, CR 82.1 μ mol/L, BUN 5.26mmol/L, ALT 30IU/L, AST 26U/L.

On JIUYUE 11st, 2011, any discomfort was not told in further consultation for the second time yet.Have a medical check-up: vital sign is normal, body weight 57kg, and the cervical lymph node size does not have obviously change, and red tongue with thin fur is white, slippery and rapid pulse.Auxiliary examination: virus load: 3938 copy/ml, CD4 509cell/ μ l, WBC 4.18 * 10 ⁹/ L, LYM 1.90 * 10 ⁹/ L, HGB 151g/L, CR 89.7 μ mol/L, BUN 7.22mmol/L, ALT 20IU/L, AST 19U/L.

Patient's cd4 cell situation is basicly stable, virus load Cong>10 ⁵Copy/ml reduces to 3938 copy/ml, all the other routine blood tests, Liver and kidney merit Non Apparent Abnormality.

Case 2: poplar, the man is 26 years old, more than the schooling junior college, married.2011.2.14 day first visit.Main suit: find HIV because of anemia and infect.Medical history situation: because of dizziness appears in hemorrhoidal hemorrhage, be diagnosed as anemia, and find the HIV positive before 1 week, blood transfusion 800ml.The route of transmission is that the same sex spreads through sex intercourse, and approximately infection time is 2 years, no vein bang history.Have a medical check-up: vital sign is normal, body weight 66kg, and pale complexion, spirit is relatively poor, surplus no special.Red tongue with thin fur is greasy, thready and moderate pulse.Auxiliary examination: virus load:>10 ⁵Copy/ml, CD4 364cell/ μ l, WBC 4.6 * 10 ⁹/ L, LYM 2.1 * 10 ⁹/ L, HGB 87g/L, CR45.9 μ mol/L, BUN 5.6mmol/L, ALT 9IU/L, AST 18IU/L.Be diagnosed as HIV and infect asymptomatic stage, deficiency of vital energy folder damp syndrome.Give the invigorating YANG detoxification particles, half an hour, warm water took after meal, and each 1 bag, 2 times on the one.

Come further consultation before 14 days Mays in 2011, do not tell special discomfort.Have a medical check-up: vital sign is normal, body weight, and 73kg, spirit is good, red tongue with thin fur, thready pulse.Auxiliary examination: virus load:>10 ⁵Copy/ml, CD4364cell/ μ l, WBC 5.7 * 10 ⁹/ L, LYM 2.7 * 10 ⁹/ L, HGB 106g/L, CR 57.7 μ mol/L, BUN 3.9mmol/L, ALT 18IU/L, AST 29U/L.

On the August 14th, 2011 of further consultation for the second time, no any discomfort.Have a medical check-up: vital sign is normal, body weight, and 72kg, spirit is good, red tongue with thin fur, thready pulse.Auxiliary examination: virus load: 2.71 * 10 ³Copy/ml, CD4 519cell/ μ l, WBC 5.2 * 10 ⁹/ L, LYM 2.7 * 10 ⁹/ L, HGB 124g/L, CR 66.6 μ mol/L, BUN 2.8mmol/L, ALT 27IU/L, AST 22U/L.

Further consultation for the third time on November 14 in 2011, no any discomfort.Have a medical check-up: vital sign is normal, body weight, and 72.5kg, spirit is good, red tongue with thin fur, moderate pulse.Auxiliary examination: virus load: 800 copy/ml, CD4 612cell/ μ l, WBC 7.2 * 10 ⁹/ L, LYM 4.0 * 10 ⁹/ L, HGB 153g/L, CR 64.8 μ mol/L, BUN 3.4mmol/L, ALT 17IU/L, AST 19U/L.

Treated 9 months, the anemia situation is improved, and virus load is from beginning>10 ⁵Copy/ml reduces to 800 copy/ml afterwards, and CD4 increases to 612cell/ μ l afterwards from the 364cell/ μ l that begins.At period in a medicine, routine blood test, Liver and kidney merit are monitored all in normal range.

Test Example 2 pharmaceutical composition immunological enhancements of the present invention

1 experiment material

1.1 medicine, reagent and instrument

1.1.1 receive the reagent thing

Pharmaceutical composition of the present invention (to call the invigorating YANG detoxification particles in the following text) is prepared by embodiment 1.1 bag of clinical consumption/inferior, 2 times/day.9 gram granule/bags, every gram granule contain primary crude drug 2.93 grams.The clinical dosage of drafting of invigorating YANG detoxification particles is gram crude drug in whole every days 52.7, and by the about 60 kilograms of calculating of the general body weight of adult, human dosage is 0.88 gram crude drug in whole/kilogram approximately.The fluid extract that does not add adjuvant with lot number is adopted in experiment, and every gram fluid extract contains crude drug in whole 3.27 grams, lot number 080804.

Get these article grinding back adding distil water during experiment and be made into the desired concn medicinal liquid; Wherein the large, medium and small dose groups of mice is respectively 17.6g/kg, 8.8g/kg, 4.4g/kg; The large, medium and small dose groups of rat is respectively 17.6g/kg, 8.8g/kg, 4.4g/kg; The large, medium and small dose groups of rabbit is respectively 13.2g/kg, 6.6g/kg, 3.3g/kg, and matched group is given distilled water.

1.1.2 medicine, reagent and instrument

SHENGMAI ZHUSHEYE, SZYY Group Pharmaceutical Limited. produces, lot number 08091104;

Aspirin tablet, Baijingyu Pharmaceutical Co., Ltd., Nanjing, lot number: 070622;

Cyclophosphamide, Hualian Pharmaceutical Co., Ltd., Shanghai produces, lot number: 020615;

Anhydrous Na ₂CO ₃, the Long Huagongshijichang of Chengdu section produces, lot number: 050406;

Xylene, Shanghai General Pharmaceutical Co., ltd., lot number 20050628;

Formaldehyde, Chengdu Noah's ark chemical reagent factory, lot number 20080623;

2,2, 4-dinitrophenol, Shanghai reagent three likes to think the production of reagent company limited, lot number 20000108;

The endotoxin lipopolysaccharide, E.coli endotoxin 055:B5; 4005, Sigma company produces;

Acetic acid, the Long Huagongshijichang of Chengdu section produces, lot number: 20050306;

Precision balance: Switzerland's prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit AB204-E type precise electronic balance

It is thus clear that uv-spectrophotometric appearance: T6 new century, Beijing Puxi General Instrument Co., Ltd

Electronic balance: the ACS-3H-B type, Zhongshan city's sharp electronic scale company limited of gold is produced

Refrigerator-freezer, the Hangzhou Bao Zhilengshebeichang that admires produces model BD-210;

The digital display electric drying oven with forced convection, the holy glad scientific instrument company limited in Shanghai is produced model 101A-3;

The tired appearance of transfer rod formula, Shandong Academy of Medical Sciences supply of equipment maintenance station produces, model XZC-4B;

1.2 animal

The SD rat, male and female half and half, body weight 180 ± 20 grams, Sichuan Academy of Medical Sciences's Experimental Animal Center provides, and the dispensing feedstuff.The quality certification number: scxk (river) 2008-24.

The KM mice, male and female half and half, body weight 20 ± 2 gram, the Sichuan Provincial Academy of Traditional Chinese Medicine Experimental Animal Center provides, the quality certification number: scxk (river) 2008-19; Sichuan Academy of Medical Sciences's Experimental Animal Center provides, and the dispensing feedstuff, the quality certification number: scxk (river) 2008-24.

Japan large ear rabbit, male and female half and half, 1.8～2.1 kilograms of body weight, plant of Sichuan Province's laboratory animal special commission provides, and the dispensing feedstuff.The quality certification number: scxk (river) 2008-14.

Feeding environment meets SPF level barrier system, credit number 057.20 ± 2 ℃ of receptacle temperature, relative humidity (70 ± 5) %.Laboratory animal divides cage to feed by sex, and every cage is raised with 5 of sex rat/mouse at most.

1.3 method and result

1.3.1 caused by cyclophosphamide mice hemolytic antibody is generated low influence

Hemolysin is a kind ofly can be incorporated into erythrocytic antibody specifically, and this antibody can cause erythrocytolysis to discharge hemoglobin, is a kind of active substance that can react immunologic function therefore.And cyclophosphamide can be in various degree the inhibition hemopoietic function of bone marrow, make PBC less, immunologic function suffers damage.This test adopts cyclophosphamide to carry out subcutaneous injection to mice; Set up the immunosuppressant model; And stimulate the mouse immune system to produce the hemolysin dissolving with chicken erythrocyte lumbar injection to discharge hemoglobin; Through the comparison of peripheral blood supernatant, estimate the immunological enhancement of immunosuppressant modelling success or not and trial drug at last.Concrete grammar is following:

60 of mices, male and female half and half are divided into 6 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), model control group, blank group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.In addition, all the other respectively organize subcutaneous injection cyclophosphamide 20mg/kg except that the normal control group, and 1 time/2 days, totally 3 times; Every Mus is with the immunity of 5% Sanguis Gallus domesticus ball 0.2ml lumbar injection behind the first administration 1h, and each Mus was got blood 20ul in eye socket on 1, adds the 1ml normal saline; Add 4% chicken erythrocyte 0.5ml, 10% GPS 0.5ml again, in 37 ℃ of water-baths, hatch 40min, the ice bath cessation reaction; In the centrifugal 10min of 2000rpm, get supernatant 1ml, add 3ml Dou Shi liquid; Mixing returns to zero with Dou Shi liquid in 540nm behind the 10min, measures and respectively manages trap.The result compares each group difference significance, inspection level α=0.05 with the t check.

The result: see table 27, the normal control group has notable difference (P＜0.01) with the model group ratio, and model group moulding success is described; Invigorating YANG big or middle dose groups of detoxifcation and model group compare, and its trap significantly increases, and shows that the invigorating YANG detoxification particles causes the mice hemolytic antibody to cyclophosphamide tangible antagonism is lowly arranged.

Table 27: the invigorating YANG detoxification particles generates low influence to caused by cyclophosphamide mice hemolysin

1.3.2 to of the influence of mice reticuloendothelial system to inertia carbon granule phagocytic activity in the blood flow

50 of Kunming mouses, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.Last administration 24h injects dilution india ink 0.1ml/10g in caudal vein, and 30s and 6min get blood 0.025ml from the mouse orbit rear vein beard after injecting prepared Chinese ink, are blown into 0.1%Na at once ₂CO ₃Among the liquid 2ml, 675nm place colorimetric on spectrophotometer is calculated phagocytic index K and is engulfed alpha, cuts open to get mouse liver, spleen, thymus and weigh, and respectively organizes difference.The result compares each group difference significance, inspection level α=0.05 with the t check.

Table 28: the invigorating YANG detoxification particles is to the influence of mice reticuloendothelial system phagocytic function

^*Compare P＜0.05 with contrast, ^*Compare P＜0.01 with contrast

The result: see table 28, big or middle dose groups of invigorating YANG detoxification particles and matched group compare, and its phagocytic index significantly increases; The heavy dose of group of invigorating YANG detoxification particles compares with matched group, and it engulfs coefficient significantly increases; Show that the invigorating YANG detoxification particles has tangible potentiation to mice reticuloendothelial system phagocytic function.

1.3.3 influence to the mice non-specific immunity

1.3.3.1 anti-refrigeration test

50 of Kunming mouses, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.Respectively each group mice is put in the cage and places refrigerator-freezer behind the last administration 1h, refrigerator-freezer temperature-6 ℃ is observed the mice active situation, stops to be decided to be mouse diing time more than 1 minute with the mouse breathing activity, respectively organizes difference.The result compares each group difference significance, inspection level α=0.05 with the t check.

The result: see table 29, big or middle dose groups of invigorating YANG detoxification particles and matched group relatively all can obviously prolong the death time of freezing induced mice, show that the invigorating YANG detoxification particles has significant protective effect to freezing induced mice death.

Table 29: the invigorating YANG detoxification particles is to the dead influence of freezing induced mice

1.3.3.2 high temperature resistant test

50 of Kunming mouses, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.Respectively each group mice is put in the cage and places baking oven behind the last administration 1h; 55 ± 1 ℃ of oven temperatures observe being found in the movable significantly increase of mice in the thermal environment, jump; Mouth nose flow liquid; Then crouch down or lie on one's side, death, stop to be decided to be mouse diing time more than 1 minute with the mouse breathing activity, respectively organize difference.The result compares each group difference significance, inspection level α=0.05 with the t check.

The result: see table 30, the heavy dose of group of invigorating YANG detoxification particles compares with matched group, can obviously prolong the death time of high temperature induced mice, shows that death has significant protective effect to the invigorating YANG detoxification particles to the high temperature induced mice.

Table 30: the invigorating YANG detoxification particles is to the dead influence of high temperature induced mice

Above-mentioned experiment shows that pharmaceutical composition of the present invention is the enhancing human body immunity effect obviously.

The constitutional effect of Test Example 3 pharmaceutical compositions of the present invention

Thymus is the most important immune organ of human body, is T cell development and sophisticated main place.After the ancestral T cell that comes from bone marrow got into thymus, under the effect of thymus microenvironment, the selection course that experience is complicated and grow and be sophisticated T cell was moved out of thymus, is settled in peripheral immune organ, participates in lymphocytic recirculation, carries out various immunologic functions.Therefore, the strong degree that the quality of thymus can the partial reaction mice; Spleen is the maximum peripheral immune organ of human body, mainly contains a large amount of B cells, also has filtration and synthetic some bioactive substance such as effects such as complement, cytokine.Liver is to be responsible for metabolic major organs in the body, is undertaking the storage glycogen, synthesizes and secrete the effect of multiple protein and cholesterol, and some metabolite in many non-nutritive substances such as various medicine, poisonous substance and the body is excreted through biotransformation.Therefore, through mensuration, react the potentiation of pharmaceutical composition of the present invention in this Test Example to body body constitution to the weight of the body weight of mice, thymus, liver spleen.

Trial drug, reagent, instrument, animal are referring to Test Example 2.

The influence of the 1 pair of normal mouse body weight and immune organ

50 of mices, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.Put to death animal behind the last administration 1h, cut open and get mouse liver, spleen, thymus and weigh, respectively organize difference.The result compares each group difference significance, inspection level α=0.05 with the t check.

Visible by table 31, table 32, the invigorating YANG detoxification particles all not have obviously to influence to the body weight and the immune organ of normal mouse.

Table 31: the invigorating YANG detoxification particles is to the influence of normal mouse immune organ

^*Compare P＜0.05 with contrast

Table 32: the invigorating YANG detoxification particles is to the influence of normal weight of mice

The have a delicate constitution influence of mice body weight and immune organ of 2 pairs of caused by cyclophosphamide

50 of mices, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.In addition, each organizes mouse subcutaneous injection cyclophosphamide 100mg/kg, and 1 time/2 days, totally 3 times; Put to death animal behind the last administration 1h, cut open and get mouse liver, spleen, thymus and weigh, respectively organize difference.The result compares each group difference significance, inspection level α=0.05 with the t check.

Visible by table 33, table 34, the heavy dose of group of invigorating YANG detoxification particles has significance to improve to the have a delicate constitution body weight of mice of caused by cyclophosphamide; The big or middle dose groups of invigorating YANG detoxification particles is to the caused by cyclophosphamide thymic weight of the mice effect that also is significantly improved that has a delicate constitution.

Table 33: the invigorating YANG detoxification particles is to the have a delicate constitution influence of mouse immune organ of caused by cyclophosphamide

Compare with matched group, ^*P<0.05, ^*P<0.01

Table 34: the invigorating YANG detoxification particles is to the have a delicate constitution influence of mice body weight of caused by cyclophosphamide

The influence of 3 pairs of normal mouse runner crawl times

Get Kunming mouse, the rotating speed of the tired appearance of YLS24C transfer rod formula is adjusted to 40 rev/mins, synchronously 5 mices are placed on the transfer rod, select and on transfer rod, to stop 50 of the mices that 30min do not fall.50 qualified mices that filter out are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.Behind the last administration 1h each group mice being placed on rotating speed is on 40 rev/mins of transfer rods, the record time of staying of mice on transfer rod, respectively organizes difference.The result compares each group difference significance, inspection level α=0.05 with the t check.The rod if mice falls in 1min, then this group mice needs to experimentize again at once.

Visible by table 35, the heavy dose of group of invigorating YANG detoxification particles has significance raising effect to normal mouse runner crawl time.

Table 35: the invigorating YANG detoxification particles is to the influence of normal mouse runner crawl time

The influence of 4 pairs of normal mouse swimming times

50 of mices, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.Behind the last administration 1h; At the load sheet lead of 5% body weight of Mus root of the tail portion; To plant mice and place the swimming case of 25 ± 1 ℃ of water temperatures, the about 30cm of the depth of water to swim, and after mice sinks under water 6s, not refloat as death standard, the record mice is from the extremely dead time of swimming beginning; As the mice swimming with a load attached to the body time, respectively organize difference.The result compares each group difference significance, inspection level α=0.05 with the t check.

Visible by table 36, the invigorating YANG detoxification particles is to the effect of improving of normal mouse swimming time, but there are no significant difference.

Table 36: the invigorating YANG detoxification particles is to the influence of normal mouse swimming time

The have a delicate constitution influence of mice runner crawl time of 5 pairs of caused by cyclophosphamide

Get Kunming mouse, the rotating speed of the tired appearance of YLS24C transfer rod formula is adjusted to 40 rev/mins, synchronously 5 mices are placed on the transfer rod, select and on transfer rod, to stop 50 of the mices that 30min do not fall.50 qualified mices that filter out are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.In addition, each organizes mouse subcutaneous injection cyclophosphamide 100mg/kg, and 1 time/2 days, totally 3 times; Behind the last administration 1h each group mice being placed on rotating speed is on 40 rev/mins of transfer rods, the record time of staying of mice on transfer rod, respectively organizes difference.The result compares each group difference significance, inspection level α=0.05 with the t check.The rod if mice falls in 1min, then this group mice needs to experimentize again at once.

Visible by table 37, the big or middle dose groups of invigorating YANG detoxification particles all has significance raising effect to the caused by cyclophosphamide mice runner crawl time that has a delicate constitution.

Table 37: the invigorating YANG detoxification particles causes the influence of the mice runner crawl time that has a delicate constitution to cyclophosphamide

The have a delicate constitution influence of mice swimming time of 6 pairs of caused by cyclophosphamide

50 of mices, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), SHENGMAI ZHUSHEYE group (20ml/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, and 1 time/day, continuous 7 days.In addition, each organizes mouse subcutaneous injection cyclophosphamide 100mg/kg, and 1 time/2 days, totally 3 times; Behind the last administration 1h; At the load sheet lead of 5% body weight of Mus root of the tail portion; To plant mice and place the swimming case of 25 ± 1 ℃ of water temperatures, the about 30cm of the depth of water to swim, and after mice sinks under water 6s, not refloat as death standard, the record mice is from the extremely dead time of swimming beginning; As the mice swimming with a load attached to the body time, respectively organize difference.The result compares each group difference significance, inspection level α=0.05 with the t check.

Visible by table 38, the big or middle dose groups of invigorating YANG detoxification particles all has significance raising effect to the caused by cyclophosphamide mice swimming time that has a delicate constitution.

Table 38: the invigorating YANG detoxification particles is to the dead influence of high temperature induced mice

Above-mentioned experiment shows that pharmaceutical composition of the present invention is enhancing body body constitution effectively.

Test Example 4 pharmaceutical composition antiinflammatory actions of the present invention

Trial drug, reagent, instrument, animal are referring to Test Example 2.

1, the influence of invigorating YANG detoxification particles xylol induced mice ear swelling

50 of mices, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), aspirin group (150mg/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, every day 1 time, 7d continuously; 60min drips xylene 0.02ml in the mouse right ear two sides after the last administration, puts to death animal behind the 30min, cuts ears along the auricle baseline; Card punch with the about 6mm of diameter is laid round auricle respectively at same position; Scales/electronic balance weighing as the swelling level index, compares the difference between administration group and matched group with two auricle weight differences.

The result sees table 39, and invigorating YANG detoxification particles heavy dose has the obvious suppression effect to the mice ear due to the group xylene.

Table 39: the influence

of invigorating YANG detoxification particles xylol induced mice ear swelling

2, invigorating YANG detoxification particles PARA FORMALDEHYDE PRILLS(91,95) causes the influence of mice foot swelling

50 of mices, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), aspirin group (150mg/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, every day 1 time, 7d continuously, after the last administration immediately in the right back foot foot of mice plantar subcutaneous injection 5% formaldehyde 0.03mL.Put to death behind the 4h, cut metapedes from the knee joint place and weigh respectively, be the swelling degree and calculate suppression ratio with the difference of two heavy sensation in the foot amounts.

The result sees table 40: the mice foot swelling that the heavy dose of group of invigorating YANG detoxification particles PARA FORMALDEHYDE PRILLS(91,95) causes has the obvious suppression effect.

Table 40: invigorating YANG detoxification particles PARA FORMALDEHYDE PRILLS(91,95) causes the influence

of mice foot swelling

Compare with matched group, ^*P<0.05, ^*P<0.01

Above-mentioned experiment shows that pharmaceutical composition of the present invention has good antiinflammatory action.

Test Example 5 pharmaceutical composition refrigeration functions of the present invention

Trial drug, reagent, instrument, animal are referring to Test Example 2.

1, the invigorating YANG detoxification particles is to 2, and 2, 4-dinitrophenol causes the refrigeration function of rat fever

2, the preparation of 2, 4-dinitrophenol solution: precision takes by weighing 2,2, 4-dinitrophenol 262.5mg; Place 120ml left and right sides normal saline, Dropwise 5 mol/L NaOH solution constantly stirs; After treating that medicinal liquid is clear and bright and becoming glassy yellow, add hydrochloric acid conditioning solution PH to 7 again, add normal saline to 150ml.

Learn from else's experience and screen the body temperature eligible, 50 of body weight 180～220 gram healthy SD rats, male and female half and half; Be divided into 5 groups at random; Every group 10, be respectively the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg); Small dose group (4.4g/kg), aspirin group (100mg/kg) and matched group.Difference ig relative medicine or normal saline 1ml/100g, every day 1 time, totally 7 days.In first three sky of experiment, survey normal body temperature, every day twice, continuous 3 days with mercury clinical thermometer (oral thermometer).Experiment is day prior to twice of administration before measurement basal body temperature; Irritate stomach respectively and give relative medicine and normal saline, back subcutaneous injection 2 immediately after the administration, 2, 4-dinitrophenol 1ml/100g; Survey body temperature once later per half an hour; METHOD FOR CONTINUOUS DETERMINATION 3 hours is calculated the body temperature changing value (Δ ℃) of rat before and after each minute administration, and is done the t check.

The result sees table 41; Rat back subcutaneous injection 2; The body temperature of rat is obviously risen, and with the invigorating YANG detoxification particles treatment of various dose, the invigorating YANG detoxification particles can obviously suppress 2 in 1.5h～2.5h after administration; 2, 4-dinitrophenol cause rat fervescence (P 0.01, P 0.05).

Table 41: the invigorating YANG detoxification particles is to 2, and 2, 4-dinitrophenol causes the influence

of rat fever

Compare with matched group, ^*P<0.05, ^*P<0.01

2, the invigorating YANG detoxification particles causes the influence of fever in rabbits to the endotoxin lipopolysaccharide

New zealand rabbit, body weight 1.5～2.0kg surveys the anus temperature every day 2 times; Continuous 3 days, choose 30 of the rabbit that body temperature fluctuation is no more than 0.3 ℃, be divided into 5 groups at random; The heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg); Aspirin group (100mg/kg), matched group.Fasting can't help water 14 hours before the experiment.Experiment is day in administration before measurement basal body temperature 2～3 times; Irritate stomach respectively and give relative medicine and normal saline (it is long-pending identical to irritate body of stomach); After the administration immediately in ear along intravenous injection endotoxin lipopolysaccharide 1 μ g/kg; Respectively surveyed body temperature 1 time in 1,2,3,4,6 hour in injection back, calculate the body temperature changing value (Δ ℃) of rabbit before and after each minute administration, and do the t check.

The result sees table 42, behind the rabbit injection endotoxin body temperature of rat is obviously risen, and the invigorating YANG detoxification particles has significant refrigeration function to fever in rabbits due to the endotoxin, and is significant dose-effect relationship.Behind administration 2h the invigorating YANG detoxification particles can obviously suppress rabbit fervescence (P 0.01, P 0.05).

Table 42: the invigorating YANG detoxification particles causes the influence

of fever in rabbits to endotoxin

Compare with matched group, ^*P<0.05, ^*P<0.01

Above-mentioned experiment shows that pharmaceutical composition of the present invention has good refrigeration function.

The analgesic activity of Test Example 6 pharmaceutical compositions of the present invention

Trial drug, reagent, instrument, animal are referring to Test Example 2.

1, the influence of invigorating YANG detoxification particles Dichlorodiphenyl Acetate induced mice writhing response

50 of mices, male and female half and half are divided into 5 groups at random: the heavy dose of group of invigorating YANG detoxification particles (17.6g/kg), middle dose groups (8.8g/kg), small dose group (4.4g/kg), aspirin group (150mg/kg), matched group.Each group is ig relative medicine 0.1ml/10g respectively, every day 1 time, and 7d continuously, after the last administration 60 minutes, the equal lumbar injection 0.75% acetic acid 0.2ml/ of each Mus was only.Observe and respectively to organize the number of times that occurs turning round body in the time and 20 minutes that writhing response (abdominal part indent, stretch hind leg, buttocks is raised) appears in mice.Respectively organize difference.The result compares each group difference significance, inspection level α=0.05 with the t check.

The result: see table 43, invigorating YANG detoxification particles heavy dose can obviously suppress the writhing response of acetic acid induced mice, has compared significant difference with matched group.

Table 43: invigorating YANG detoxification particles Dichlorodiphenyl Acetate causes the influence

of mouse writhing reaction

Above-mentioned experiment shows that pharmaceutical composition of the present invention has good analgesic activity.

The effect experiment conclusion:

Above-mentioned effect experiment presentation of results:

(1) invigorating YANG detoxification particles causes the mice hemolytic antibody to cyclophosphamide lowly has tangible antagonism; The mice reticuloendothelial system has obvious potentiation to inertia carbon granule phagocytic activity in the blood flow, and making phagocytic index and engulfing coefficient significantly increases.

(2) invigorating YANG detoxification particles can obviously improve the mice non-specific immunity, can obviously prolong the death time of freezing induced mice and the death time of high temperature induced mice.

(3) invigorating YANG detoxification particles does not all have obviously influence to the body weight of normal mouse and immune organ, but have a delicate constitution body weight and the thymus index of mice of caused by cyclophosphamide all is significantly increased; The invigorating YANG detoxification particles has significance raising effect to normal and the caused by cyclophosphamide mice runner crawl time that has a delicate constitution; The invigorating YANG detoxification particles is to the effect of improving of normal mouse swimming time, but there was no significant difference, but has significance to improve to the caused by cyclophosphamide mice swimming time that has a delicate constitution.

The mice foot swelling that (4) invigorating YANG detoxification particles xylol induced mice ear swelling and PARA FORMALDEHYDE PRILLS(91,95) cause all has the obvious suppression effect, shows that the invigorating YANG detoxification particles has certain antiinflammatory action.

(5) invigorating YANG detoxification particles can obviously suppress 2, and 2, 4-dinitrophenol causes the effect of rat fever, fever in rabbits due to the endotoxin is also had significant refrigeration function, and be significant dose-effect relationship.

(6) invigorating YANG detoxification particles heavy dose can obviously suppress the writhing response of acetic acid induced mice, explains that the invigorating YANG detoxification particles has certain analgesic activity.

In sum, pharmaceutical composition of the present invention can enhancing human body immunity and body constitution, has antiinflammatory, analgesic, analgesic activity, can reduce HIV virus load in HIV carriers' body, and is stable or increase HIV carriers CD4 ⁺The T lymphocyte quantity prolongs or stable AIDS asymptomatic stage, reduces HIV carriers and gets into the probability of AIDS period of disease, helps delaying patient's morbidity process, has improved patient's quality of the life, for clinical application provides a kind of new selection.

Claims

1. invigorating YANG antidotal pharmaceutical composition, it is characterized in that: it is the preparation that is prepared from following materials of weight proportions medicine:

2. pharmaceutical composition according to claim 1 is characterized in that: it is the preparation that is prepared from following materials of weight proportions medicine:

3. pharmaceutical composition according to claim 2 is characterized in that: it is the preparation that is prepared from following materials of weight proportions medicine:

4. according to any described pharmaceutical composition of claim 1-3, it is characterized in that: it is to be active component by the water of said raw medicinal material fine powder or raw material or extractive with organic solvent, adds the preparation that adjuvant pharmaceutically commonly used is prepared from.

5. pharmaceutical composition according to claim 4 is characterized in that: said preparation is tablet, powder, capsule, granule, pill or oral liquid.

6. pharmaceutical composition according to claim 5 is characterized in that: in the said granule, contain baicalin 120 ~ 140mg in every 9g granule.

7. any described preparation of drug combination method of claim 1-3, it is characterized in that: it comprises following operating procedure:

(1) weighting raw materials by weight ratio;

8. preparation of drug combination method according to claim 7 is characterized in that:

The concrete operations of step (2) are: get the Rhizoma Pinelliae, Herba Scutellariae Barbatae adds alcohol reflux 3 times, first and second time adds 10 times of amount 50% ethanol, adds 70% alcohol reflux for the third time; Each 1 hour, filter merging filtrate; Filtrate recycling ethanol is not to there being the alcohol flavor, and concentrated solution is subsequent use;

In the step (4), Cornu Cervi Pantotrichum adopts the micronizing method to pulverize.

9. the purposes of any described pharmaceutical composition of claim 1-6 in the medicine of preparation treatment AIDS.

10. purposes according to claim 9 is characterized in that: said medicine is the medicine of treatment AIDS asymptomatic stage.

11. according to claim 9 or 10 described purposes, it is characterized in that: said medicine is anti HIV-1 virus, stable or rising AIDS virus carrier CD4 ⁺The medicine of T lymphocyte quantity.

12. any described pharmaceutical composition of claim 1-6 is at preparation enhance immunity, antiinflammatory, analgesic or/and the purposes in the medicine of analgesic.