CN1119156C

CN1119156C - Xiancaoteng capsule made of korean epimedium herb, liquorice root and common threewingnut root and its preparation

Info

Publication number: CN1119156C
Application number: CN00101587A
Authority: CN
Inventors: 辛耀禄
Original assignee: Individual
Current assignee: Individual
Priority date: 2000-01-27
Filing date: 2000-01-27
Publication date: 2003-08-27
Anticipated expiration: 2020-01-27
Also published as: CN1265318A

Abstract

The present invention provides a Xiancaoteng capsule and a preparation method thereof. The Xiancaoteng capsule contains epimedium (epimedium herb) radix glycyrrhiza and common threewingnut root. Effective constituents of the components are respectively prepared, and finally, the Xiancaoteng capsule is prepared according to the clinical optimum dosage. The Xiancaoteng capsule is mainly used for invigorating the kidney to cure connective tissue diseases and immunological diseases, can cure stubborn diseases of connective tissue diseases, such as rheumatoid arthritis, ankylosing spondylitis, lupus erythematosus, etc., and has the advantages of reasonable prescription, advanced extraction technology, advanced processing technology, high curative effect, small side effect, wide medicine source and low price.

Description

Herba mesonae chinensis liana rubber capsule and preparation method thereof

The present invention relates to the kidney invigorating is the medicine of main treatment connective tissue disease and immune disease, i.e. Herba mesonae chinensis liana rubber capsule.

At China's field of medicaments, Chinese medicine research is flourish with unprecedented scale, and millions upon millions of medical science men are arranged, and with clever ability and intelligence, superb technology is researched and developed new drug night and day, and national hygiene and health cause is contributed in order to rejuvenate China.Aspect treatment connective tissue diseases such as " rheumatoid arthritis, ankylosing spondylitis, lupus erythematosus " and immune disease, existing pharmaceutical effectiveness is not high, and toxic and side effects is big, can not reach effective therapeutic purposes.

It is the Herba mesonae chinensis liana rubber capsule of main treatment connective tissue disease and immune disease with the kidney invigorating that purpose of the present invention just provides a kind of, connective tissue diseases such as " rheumatoid arthritis, ankylosing spondylitis, lupus erythematosus " can cure difficult and complicated cases, reasonable recipe, extraction processing technique advanced person, the curative effect height, toxic and side effects is little, and the medicine source is wide, and is cheap.

For achieving the above object, the present invention is by the following technical solutions:

A kind of Herba mesonae chinensis liana rubber capsule is characterized in that prescription consists of Herba Epimedii, Radix Glycyrrhizae, Radix Tripterygii Wilfordii.

Its preparation method is realized by following processing step:

(1) Herba Epimedii extraction process:

(1) Herba Epimedii crude product extraction process: the former medicine of rough lumber adds 8 times of amount 1% sulphuric acid water, keeps 80 ℃ of reflux, extract, 3 hours, and the leaching medicinal liquid is put in addition; Residue adds 5 times of amount 1% sulphuric acid liquid again, extracts 2 hours by same operation, and continuous 2 times, multiple leaching medicinal liquid and preceding liquid merge, and gather repeatedly sour water extract, are condensed into than the 1.1-1.2 that weighs; Add 95% ethanol equivalent precipitated impurities, left standstill 12-14 hour, extract supernatant liquid filtering, precipitation is washed 2-3 time with 45% hexanol, and solvable composition washes out in will precipitating, and filtrate and washing liquid merge, and reclaims ethanol, and concentrating under reduced pressure is cooled to cream;

(2) the pure product extraction process of Herba Epimedii Saponin: Herba Epimedii crude product extractum adds 70%4 times of amount ethanol, and reflux 2 hours is filtered, and filtering residue adds 2 times of amount alcohol refluxs 1 hour again, filters, and reclaims ethanol, 60 ℃ of dryings;

(3) epimedium brevicornum polysaccharide extraction process: Herba Epimedii is pulverized coarse powder and is added 5 times of amounts of 75% ethanol 0.5NHaoH reflux 2 hours, filters, and extracts three times with method, merging filtrate is condensed into cream, add 95% ethanol with being stirred to precipitation, spending the night, filtering, reclaim ethanol, continuous 2 times; Add 2 times of amounts of water,, get pure product epimedium brevicornum polysaccharide with DEAE cellulose (phosphate type) column chromatography purification;

(2) extraction process of Glycyrrhiza uralensis:

(1) thick glycyrrhizic acid extraction process: thick Radix Glycyrrhizae powder is with 12 times of amount 0.5% ammonia seepages, and continuous 3 times, effusion is concentrated into original volume 1/5 and filters, and filtrate adds concentrated sulphuric acid to PH3, and the precipitation that filtration is separated out is washed 3 times, drying below 60 ℃ both thick glycyrrhizic acid;

(2) pure product glycyrrhizic acid extraction process: the thick glycyrrhizic acid 400g of above gained, add 4 times of amount ethanol, reflux 3 hours is filtered, filtering residue adds 2 times of amount alcohol refluxs 2 times, merge backflow and add the 10g active carbon, reflux decolour cooling half an hour, filtration, the logical ammonia of filtrate is to PH7-7.5, till no solid is separated out, the filtrate precipitation with small amount of ethanol washing, drying at room temperature, gets ammonium glycyrrhizinate 250g;

(3) the pure product glycyrrhizic acid of injection white crystals: the ammonium glycyrrhizinate 250g that the preceding step obtains, continue 80% ethanol with 4 times of amounts, heating for dissolving is also used activated carbon decolorizing, and cold filtration reclaims ethanol, and filtrate concentrates, and separates out white crystals;

(4) Radix Glycyrrhizae residue and precipitate, extract glycyrrhizic acid, glycyrrhizic acid calcium, licoflavone: it is solvent that Radix Glycyrrhizae residue and precipitate add 1%H2SO4-70% ethanol, after the hot dipping 8 hours, reflux 2 hours is filtered continuous 2 times, merge overanxious, reclaim ethanol, be condensed into cream, reclaim simultaneously glycyrrhizic acid, glycyrrhizic acid calcium, licoflavone;

(3) tripterygium glycosides extraction process:

(1) the Radix Tripterygii Wilfordii coarse powder is measured reflux, extract, for 5 times with 85% methanol, filtered while hot, and medicinal residues add fresh solvent again, and reflux, extract, is 3 times repeatedly, and each 4 hours, merge 4 times methanol extract liquid, reclaim methanol, concentrating under reduced pressure promptly gets thick general glycoside extractum; (because of Saponin dissolves in hot alcohol, both separated out after cold, used hot alcohol reflux extracts);

(2) thick Saponin extractum is dissolved in water, the back with droplet countercurrent chromatography (D.C.C-A type) solvent system be chloroform-methanol-n-butyl alcohol-water (volume ratio was pressed 45: 60: 6: 40), lower floor's phase that fixes, mobile phase is made on the upper strata, stripping solution is collected with collecting instrument automatically step by step, reclaims solvent; N-butanol extracting liquid, washing back concentrating under reduced pressure promptly gets the genuine soap glycoside;

(3) for preventing to contain residual n-butyl alcohol, technology adopts the Diluted Alcohol Retreatment method at last, and to shorten drying time, it is residual to remove n-butyl alcohol, promptly gets pure product Radix Tripterygii Wilfordii glycoside;

(4) Herba mesonae chinensis liana rubber capsule preparation technology: icariine 50mg/kg/ day, epimedium flavone 20mg/kg/ day, epimedium brevicornum polysaccharide 20mg/kg/ day; Glycyrrhizic acid 50mg/kg/ day, licoflavone 10mg/kg/ day, Radix Tripterygii Wilfordii glycoside 1.5mg/kg/ day; All calculate consumption, amount to 7575mg/50kg/ day, be divided into and adorn 16 large size capsules, each capsule dress 473.43mg by the 50kg body weight.

The present invention has following remarkable result:

1, the present invention has novelty, reasonable recipe, efficient, low toxicity: form by Herba Epimedii (having another name called Herba Epimedii), Radix Glycyrrhizae, Radix Tripterygii Wilfordii, do not see with the kidney invigorating to be main treatment connective tissue disease and immune disease in the prior art, and clinical cure rate, obvious effective rate, effective percentage are very high, and toxic and side effects is very little.As treat rheumatoid arthritis and ankylosing spondylitis.(1) prescription provided by the present invention has very strong kidney invigorating and YANG supporting, bone and muscle strengthening, benefit essence, mends waist knee joint, blood circulation promoting and blood stasis dispelling, wind-damp dispelling cold expelling, eleminating phlegm and freeing channels effect, and very strong Detoxication is arranged.To pathogen usually intruding into collateral in protracted disease, prolongedly do not heal, phlegm and blood stasis, the disease of vital QI being weakened and pathogen being violent has unique curative effect.Promote the synthetic and protein synthesis of DNA, promote normal bone growth and both injured bones to recover healthy and strong, especially rheumatoid arthritis and ankylosing spondylitis are really reached efficient, unique excellent results.(2) efficient: clinical efficacy is than single clothes Radix Tripterygii Wilfordii height, and according to 236 routine clinical treatment observations, clothes " Herba mesonae chinensis liana rubber capsule " had 98% people can reach pain relieving in 3-7 days, the detumescence rate reaches 87% in 7 days, cure rate reaches 52.12%, and obvious effective rate reaches 79.31%, and effective percentage reaches 96.91%, the rheumatoid factor negative conversion rate reaches 76.6%, control ankylosing spondylitis 129 examples altogether, cure rate 55.81%, obvious effective rate 32.56%, improvement rate 9.3%, total effective rate 97.67%.Cure rate+obvious effective rate=88.37%, all single clothes Radix Tripterygii Wilfordii height." Herba mesonae chinensis liana rubber capsule " really reaches effect unique efficiently.(3) low toxicity: in the past single clothes Radix Tripterygii Wilfordii tablet or capsule 80 days, the heart, liver, kidney, reproductive system all have and damage pathological changes in various degree, and toxic and side effects reaches 30-68.46%, and reproductive system damages 84%.Control rheumatoid arthritis and ankylosing spondylitis clothes " Herba mesonae chinensis liana rubber capsule " now and serve on 180 days, increase by 1.66 times medicine time than in the past, after testing: the heart, liver, kidney, reproductive system organ pipe all do not have obvious damage." Herba mesonae chinensis liana rubber capsule " no serious toxicity is described, just groups of people have lighter gastrointestinal reaction, formerly have the inclination, the liver patient, and one or two people respond.But the people to reproductive system 1-2% responds or the hyposexuality phenomenon, and one or two people have cacospermia.All women do not have amenorrhea or uterus loss of weight etc., illustrate that toxicity is very low.

2, prescription three flavor medicine extraction process advanced persons provided by the present invention, purity height are so toxic and side effects is little; Particularly the Radix Tripterygii Wilfordii glycoside is with droplet countercurrent chromatography (D.C.C-A type) purity height, so toxicity is low.

3, to be purified to the branch prescription reasonable for the new Chinese medicine of the present invention: because excessive half leaves of pulse plants glycoside, epimedium flavone, Herba Epimedii acid polysaccharide, glycyrrhizic acid (glycyrrhizin), licoflavone, Radix Tripterygii Wilfordii glycoside (because of toxicity minimum: Radix Tripterygii Wilfordii glycoside＜triterpenes＜alkaloid＜Diterpenes) three kinds of medicines all are that glycoside and flavonoid are formed, so there is not incompatibility, efficacy stability has synergism.

4, the present invention has strong antiinflammatory action: suppress immunoreation, immunological enhancement is arranged again, humoral immunization and immunization of cell are arranged, dual regulation, can induce r-interferon (IFN-r), interleukin II (IL-2), interleukin 3 (IL-3), tumor necrosis factor is in (TNF-a), β 1-transforming factor (TGF-B1), HIV-1 inhibitive factor, natural killer cell (NK cell), these immunologic active materials are to regulating immunity, suppress tumor, suppressing HIV has remarkable effect, and the treatment to connective tissue disease and immune disease has obtained effect unique especially.

5, the present invention has strong antitumor and anti-AIDS toxic action: three medicines all have very strong anti-tumor activity, suppress and the killing tumor cells target cell, and can suppress HIV propagation, suppress the HIV transcriptase.

6, prescription provided by the present invention has very strong Detoxication: can remove the toxicity of Radix Tripterygii Wilfordii to the heart, liver, kidney, endocrine and reproductive system.Herba Epimedii has promotion and potentiation to endocrine function: as urge excessive effect, and promote epididymis, seminal vesicle to grow.The women is improved hypophysis to luteinizing hormone releasing hormone LRH reactivity, can strengthen antepituitary, ovary, uterus weight etc.Antagonism or says that the releasing Radix Tripterygii Wilfordii is to the toxicity of the heart, liver, kidney, endocrine reproductive system.It is stronger that Radix Glycyrrhizae is removed the effect of Radix Tripterygii Wilfordii; Radix Glycyrrhizae complex (LX) has protective effect to the heart, liver, kidney, hormonal system; Radix Tripterygii Wilfordii institute proarrhythmia there is protective effect; cardiac contractile force is strengthened; infringement has protective effect to reproductive system; anti-injury effect, Radix Glycyrrhizae has dual regulation according to dosage to man, female reproductive system system.

7, the present invention has antibiotic, antifungal, antivirus action: can suppress golden Portugal bacterium, streptococcus, fungus and virus function, HIV is had strong inhibitory action, and can suppress the HIV transcriptase.

8, method of administration provided by the present invention is the innovation of extract oral method: three kinds of medicines are formed capsules, calculate dose by 50 kg body weight, and day once or part vic; Owing to press the growth and proliferation of cell cycle, so took medicine in 2-3 days one day, medication had both reduced toxic and side effects like this, make intermission 1-2 days normal cell recover active again, cell proliferation reaches the strong immunosuppressive action of medication period, intermittently the strong immunological enhancement of withdrawal time, secretion IFN-r, IL-2, NK, TNF-α etc., raise immunity again.

9, wide, the cheap and curative effect height in medicine of the present invention source, toxic and side effects are little, easy to utilize.

Now that pharmacology of the present invention, clinical practice, toxic and side effects brief introduction is as follows:

One, the pharmacological action of prescription of the present invention:

1, endocrine function is had promotion and potentiation: (1) can promote gonepoiesis, and prostate, seminal vesicle and levator ani weight are increased.(2) urge excessive effect: make gonepoiesis hyperfunction, the neural and excited libido of sensation.(3) generation of promotion male's testosterone (TS) secretion and CAMP.(4) can improve the reactivity of hypophysis to luteinizing hormone releasing hormone LRH to the women, and the reactivity worth that corpus luteum generates plain LH obviously increases antepituitary, ovary, uterus weight, after taking medicine, ovary HCG, LH receptor-specific adhesion improve 3 times.

2, immunologic function there is potentiation: to kidney deficiency human T-cell number, pouring rate of rotation, antibody, antigen and reticuloendothelial system phagocytic hypofunction person, the every index in clothes " Herba mesonae chinensis liana rubber capsule " back is improved, Histological change and minimizing extracellular matrix to kidney produce, and immunity of organism is had facilitation.

3, low concentration increases Ea bow structure rate, and high concentration reduces Ea bow structure rate, and the effect of low concentration enhance immunity is described, high concentration suppresses immunization, and immunity is had dual regulation.

4, immunoglobulin is influenced: immunoglobulin (1g) has harmful substance invasion and attack such as antagonism alien bacteria, virus, various toxin, keeps the various important function such as stable and immune surveillance of biology self.The patient measures its value under normal value at take medicine preceding 1gG, 1gA, and clothes " Herba mesonae chinensis liana rubber capsule " back 1gG, 1gA content obviously increase.It is the life-prolonging performance that old people 1g increases.

5, contained flavonoid composition has enhancing and inhibitory action to immunologic function in the prescription: total flavones can improve the serum hemolysin antibody horizontal, increases the antibody-producting cell number, promotes to drench rate of rotation, increases macrophage phagocytic function.But high concentration strong inhibition lymphocyte is to the breeder reaction of ConA, LPS, mixed lymphocyte reaction.Total flavones suppression ratio and drug level are proportional.Simultaneously can prolong the allogeneic mouse heart transplanting survival phase.

6, polysaccharide can suppress the destruction of Radix Tripterygii Wilfordii to hemopoietic system, marrow hemopoietic stem cells in the prescription.Make spleen lymphocyte proliferation, produce interleukin II (IL-2), polysaccharide has the effect of the immunne response of promotion, simultaneously can the enhance immunity memory function.And can increase luring property of ConA r-interferon (IFN-r) and IL-2.

7, prescription has the steroid hormone effect: and can stimulate hypothalamus-hypophysis-hypothalamic pituitary adrenal axis excitement, and impel the secretion of adrenal cortex releasing hormone (CRH) to increase, or optionally excited suprapituitary crh receptor, indirect action is in the adrenal gland and secreting hormone.Effect is played in the increase of adrenocortical hormone content in the body: (1) antiinflammatory action.(2) immunosuppressive action.(3) antitoxin effect.(4) Antishock function.(5) to metabolic effect.(6) to lymphocyte and blood cell effect.

8, prescription has very strong immunosuppressive action and antiinflammatory action: analgesia, analgesic, calm, spasmolysis reach 98% to rheumatoid arthritis 3-7 days pain relieving rates, the detumescence rate reaches 88% in 7 days, cure rate reaches 52%, obvious effective rate reaches 78.6%, effective percentage reaches 98.3%, and the rheumatoid factor negative conversion rate reaches 76.6%.

9, antitumor action and anti-HIV effect: this can suppress ConA and LPS to lymphocytic propagation, suppresses and kills the tumor target cell.It is to suppress PHA to induce down transcribing of cell IL-2mRNA and IL-2RP55mRNA that HIV propagation is had very strong inhibitory action, Radix Tripterygii Wilfordii glycoside T1, and it is the strongest that inhibitory action is induced to end effect in the 12nd hour at PHA.T1 is to CD ₄₊Cell and CD ₈₊Cell all has obvious inhibitory action, to CD ₄₊Cyto-inhibition is the strongest.

10, prescription is controlled connective tissue disease pharmacology, rheumatoid arthritis, lupus erythematosus etc.: this specific antibody that can suppress the anti-sheep red blood cell (SRBC) of antigen binding cell and antibody secreting cell produces, the synthetic feedback approach of 1gG antibody in the blocking-up rheumatoid arthritis patients body, and disease is eased.Also can make immunoreation trend hyperfunction in the body normal, clothes " Herba mesonae chinensis liana rubber capsule " back patients serum 1gG, 1gM, 1gA all reduce, and rheumatoid factor (RF) titre lowers or turns out cloudy, and the inhibition antibody nucleus formation of this Fang Youqiang is described.

Two, single pharmacological action:

(1) Herba Epimedii pharmacological action:

1, endocrine function is had promotion and potentiation: (1) Herba Epimedii aqueous extract can promote the dog testicular fluid secretion, after extract is given injected in mice, prostate, seminal vesicle and levator ani weight increase, its vigor of injection icariine 20-40mg/kg can be suitable with the 7.5mg testis, is equivalent to the androgen effect.(2) Herba Epimedii is urged excessive effect: be because gonepoiesis is hyperfunction, and after seminal fluid is full of, sensation nerve, indirect excitation libido and causing.(3) icariine (ICA): can obviously promote the growth of mouse epididymis, seminal vesicle, can obviously promote the basal secretion of testosterone (Ts) and the generation of CAMP: alcohol extract can promote the stimulation secretion of basal secretion and the human chorionic gonadotropin of Ts, and can the secretion of TS be increased by the CAMP approach.(4) Herba Epimedii is to hypothalamus-hypophysis-gonad axis function.The Herba Epimedii extracting solution: the 1ml/100g body weight is given female rats, and mensuration can improve hypophysis to the reactivity that reactivity and the corpus luteum of luteinizing hormone releasing hormone LRH generates plain LH after 5 days, can obviously strengthen anterior pituitary of rat, ovary, uterus weight.Ovary HCG, LH receptor-specific adhesion improve 3 times approximately after taking medicine.Illustrate that Herba Epimedii has potentiation to the secretory function of hypothalamus-hypophysis-secretion systems such as gonad axis.

2, immunologic function is had potentiation: (1) immunologic function reduces, and particularly kidney deficiency human T-cell quantity is drenched rate of rotation, antibody, antigen and reticuloendothelial system phagocytic hypofunction, and all can improve for kidney-reinforcing drug treatment such as Herba Epimedii.Mice 0.5ml lumbar injection has facilitation to immunity of organism, and Herba Epimedii can obviously alleviate the Histological change of kidney and reduce the extracellular matrix generation.(2) Herba Epimedii water decoction concentration 5mg/ml can increase Ea bow structure rate, and 50mg/ml concentration can reduce Et bow structure rate.Prompting Herba Epimedii low concentration has the Ea of promotion bow structure rate to form, and high concentration suppresses the ANAE active function.(3) Herba Epimedii is to the influence of immunoglobulin: immunoglobulin (1g) has the invasion and attack of harmful substances such as antagonism alien bacteria, virus, keeps biological self various important function such as stable and immune surveillance.Measure its value before 62 routine 1gG, 1gA take medicine under normal value, 1gG, 1gA content obviously increase in the clothes Herba Epimedii bleeding from anus, and old people's immunoglobulin increases, and are the life-prolonging performances.

3, Herba Epimedii total flavones is to Immune Effects: (1) total flavones can improve mice serum hemolytic antibody level, increases spleen antibody-producting cell number, promotes the lymphocyte transfer reaction that PHA stimulates, and increases macrophage phagocytic function.But 50% methanolic extract total flavones strong inhibition mouse lymphocyte is to the survival period of breeder reaction and the heart transplantation of mice allogeneic of COnA, LPS.(2) total flavones is to the T lymhocyte transformation rate: the lower old people of the total active rosettes of rosettes (EtRFC) (EaRFC) T lymphocyte conversion ratio (LBT) value, not only improved clinical symptoms after taking medicine 3 months, and human T-cell's immunologic function is had obvious enhancing.

4, epimedium brevicornum polysaccharide (RPS) has antagonism to azidothymidine AZT inhibition mice hemopoietic and immunologic function: (1) gives mice azidothymidine AZT 80mg/kg, its peripheral blood cells, marrow hemopoietic stem cells and grain monosystem CFU-GM quantity, the ability of spleen lymphocyte proliferation and generation interleukin IL-2 (IL-2) significantly reduces.Give epimedium brevicornum polysaccharide 10-20mg/kg, above-mentioned azidothymidine AZT toxic and side effects can partly or entirely disappear.EPS has the effect of the immunne response of promotion to humoral immune reaction for the first time or once more, also can increase the immunological memory function simultaneously.(2) injected in mice EPS10-50mg/kg, thymus dwindles L ₃, T ₄And Lrt ₂₊Cell number reduces the mitogen irritant reaction is reduced, but this moment, thymocyte proliferation improved with generation IL-2 ability.The subcutaneous injection of 100mg/kg causes that mouse thymus discharges increase, enhancing body cellular immune function and organ immunologic function.(3) EPS produces the human IL-2 regulating action: 2500-5000vb/ml concentration cell survival rate is respectively 94% and 93%, is that immune molecule is learned one of basis to active adjusting of human IL-2.(4) Herba Epimedii has dual regulation to immunity: the Ea rosette test is to measure human T-cell's common method, at low concentration 5mg/ml the Ea of increasing bow structure rate is arranged, the proof Herba Epimedii has dual regulation, methanol. and extract can strengthen the phagocytic function of mice inflammation emigrated cell.The Herba Epimedii raise immunity mainly is by reduction cell CAMP level, the ratio of rising CGMP level and CAMP/CGMP, thus influence lymphocytic nucleic acid metabolism, promote lymphopoiesis.

5, heart ischemia is had protective effect, coronary blood flow increasing: the quiet notes of (1) Herba Epimedii cause that to pituitrin myocardial ischemic injury has protective effect.The dirty perfusion 200% Herba Epimedii liquid 0.5ml of guinea-pig heart can make coronary flow increase by 126.6%.The Cor Canitis coronary flow increases by 134.6%, and the Cor Leporis coronary flow improves 66%, and can reduce resistance 68%, reduces left diastolic pressure, to Myocardial Ischemia rat blood supply insufficiency.Improve myocardial ischemia, reduce oxygen consumption and arrhythmia.(2) 1.5 * 10 ^-3G/kg adds cardiac stimulant contractility, 5 * 10 ^-3G/kg then suppresses the contractility of the heart.The 10g/kg water decoction has the anti-effect of quivering, and the anti-function of quivering of Herba Epimedii may work by the excited vagus approach.(3) Herba Epimedii has blood vessel dilating to suppress the vascular smooth muscle contraction: Herba Epimedii has the outer Ca of the vascular smooth muscle cell of inhibition ²⁺Interior stream effect can reduce high K ⁺Due to TA, MA and CA, the contractile response of CBA due to the 5-HT.(4) hypotensive effect: the Herba Epimedii decoct all has hypotensive effect for rabbit 2.5ml/kg, cat 2mg/kg, the quiet notes of rat 4ml/kg.(5) the numerous collection effect of antiplatelet: can reduce the inductive platelet aggregation rate of ADP, and certain depolymerisation is arranged, prevention thrombosis, prevention angina pectoris and arrhythmia, the polysaccharide effect is the strongest, and inferior is decoct and flavone.

6, Herba Epimedii promotes DNA synthetic: the promote osteogenesis effect, promote the albumen anabolic effect: (1) selects for use the ribonucleotide reductase inhibitor hydroxyurea to make the yang deficiency animal model, with the method that participates in DNA (deoxyribonucleic acid) (DNA) in tritium-labeled thymus nucleoside (3H-TDR) body, the research Yang-strengthening drug influences the yang deficiency animal, Herba Epimedii has the DNA of promotion anabolic effect, the bioactie agent that contains a kind of activated oligonucleotide reductase in the Herba Epimedii, thereby anti-hydroxyurea is to the inhibitory action of ribonucleotide reductase, guarantee that nucleotide reducing becomes Deoxydization nucleotide, and promote that TdR mixes DNa, finally promote DNA synthetic.The polysaccharide in vitro tests can make that the yang deficiency bone marrow cells in mice rate of increase improves 72% due to the hydroxyurea, and the DNA synthetic ratio improves 68%.And can promote protein synthesis.(2) the Herba Epimedii extracting solution has the growth of promotion effect to bone; Can promote the growth of testis rat bone, oral extracting solution, continuous 7 weeks of 5g/kg, yang deficiency group bone lengthening value improves 42%, and injection has the growth of promotion effect, medication group femur length to Embryo Gallus domesticus femur in vitro, dry weight and 38S mix all obviously increases such as intensity, and promote protein synthesis.

7, antiinflammatory action: (1) mice Ovum Gallus domesticus album swollen feet, subcutaneous injection 50mg/kg can significantly reduce the swollen feet degree.Rabbit 15g/kg can reduce capillary permeability due to the histamine.(2) Guillain-Barre syndrome (GBS) there is certain therapeutical effect, and certain immunoregulation effect is arranged.Can improve dense, sticking, the poly-state of rat blood, improve effects such as mouse ear microcirculation, increase the phagocytic function of mice inflammatory exudation cell, have antiinflammatory action.The Herba Epimedii injection has the highly significant facilitation to Embryo Gallus domesticus femoral growth in vitro, and Embryo Gallus domesticus bone protein polysaccharide synthetic had obvious facilitation.

8, Herba Epimedii is to the maincenter effects on neural system: improve the mice hypoxia-bearing capability, prolonged survival period has calmness and anticonvulsant action, and the m receptor of adjusting CGMP systemic effect is arranged, and nervus centralis is had inhibitory action.

9, anti-aging effects: (1) Herba Epimedii defying age mechanism, promote passage, prolong trophophase, regulate immunity and excretory system, improve each organ pipe function such as the heart, brain, kidney, liver, reduce the lipofuscin content of brain, the heart, liver, G in the blood, total complements etc. increase neutrophilic granulocyte and peritoneal macrophage increased functionality, and suppress thrombosis.(2) epimedium flavone has the spleen of enhancing bone-marrow-derived lymphocyte propagation function, can also obviously improve the activity of the total SOD of liver, and the lipofuscin of tissues such as the heart of minimizing LPO, liver forms, and the prompting total flavones improves the activity of SOD enzyme.Eliminate free radical, protected cell to exempt from infringement, delay organ and body aging effect.(3) Herba Epimedii can keep the normal adrenal cortex function of people and regulate immunologic function, postpones ager process and the generation that prevents senile disease.Total flavones has the T cell of enhancing and B cellular immunization and adrenal cortex function, and delaying senility function is relevant with function of immune system.(4) antifatigue effect: give the mice Herba Epimedii total flavones, 0.06 or 0.3g/kg/ day, 11 days, experiment in 1 hour after the last administration: administration 0.06g group swimming time 370.5 ± 108.2 seconds.0.3g organize 398.0 ± 109.1 seconds.Matched group 152.6 ± 45.5 seconds.Total flavones prolongs the mice swimming time, and antifatigue effect has been described.

10, pharmacokinetics: trace manganese for dynamics research, is a monitoring means with the Catalytic-Kinetic Analysis at Sanguis Leporis seu oryctolagi Chinese medicine in the Herba Epimedii, utilizes the catalytic action of divalent manganesetion to Potassium metaperiodate .-rhodamine B reaction system.Use Phen to be activating agent, trace manganese in the Sanguis Leporis seu oryctolagi has been carried out fluoremetry, curve MICROCOMPUTER PROCESSING as a result when having drawn medicine, physiological disposition meets two Room open models, and obtains serial pharmacokinetic parameter.

11, toxicity, side effect: (1) excessive pass leaves of pulse plants extractum mouse peritoneal injection LD ₅₀Be 36.Extract the LD of the quiet notes of non-amino acid moiety (NO5-1-1) mice in the aqueous extract sheet ₅₀Be 56.8 ± 2.7.It is normal that this product methanol extract liquid mouse gavaging 450mg/kg observes activity as a result in 3 days continuously, no toxicity.(2) Herba Epimedii total flavones acute toxicity test: LD ₅₀Be the acute or subacute toxicity test of 2.99 ± 0.14g/kg: the extracting solution various dose is taken continuously, tissues such as animal heart liver,kidney,spleen is not had obviously change the harmless change of cell tissue outward appearance.

(2) the contained glycyrrhizic acid of Radix Glycyrrhizae (glycyrrhizin) glycyrrhizin, licoflavone, pharmacological action:

1, to the immunologic function systematic influence: (1) has anti-allergic effects: complex that Radix Glycyrrhizae is extracted (LX) contains protein; nucleic acid; polysaccharide; glycyrrhizic acid has strong anti-allergic effects; the mouse allelgic shock also there is protective effect, a variety of causes is caused that anaphylactic shock and dead suppression ratio are more than 95%.Glycyrrhizic acid 25-50 can significantly suppress anaphylaxis, can stop sensitive media to discharge.(2) non-specific immunity is influenced: 1. glycyrrhizin can strengthen the reticuloendothelial system activity, and total white blood cells is strengthened, neutrophil, and the mononuclear cell increase is more obvious, and the stimulation macrophage phagocytic function is arranged.2. reticuloendothelial system and natural killer cell activity are had remarkable potentiation: glycyrrhizic acid and glycyrrhizin have activation to reticuloendothelial system, and the mice natural killer cell activity is had remarkable potentiation.(3) to the influence of complement: Radix Glycyrrhizae intramuscular injection CP50 and AP50 all can suppress 50% haemolysis, can suppress complementary reaction, and the related inflammation process is alleviated and be static.(4) influence of antagonist 1. glycyrrhizic acid antibody is significantly increased, 30mg/kg can make antibody produce significantly to strengthen.2. antagonist produces inhibitory action, Radix Glycyrrhizae inhibition 1gE is synthetic is that T is cell-mediated, and and CD ⁸⁺Cell is relevant.3. the Radix Glycyrrhizae antagonist produces dual regulation: both the reaction to cause of disease had potentiation, and the allergy of abnormality then is inhibitory action.(5) to the generation of interleukin II with induce the effect of r-interferon: glycyrrhizic acid 100vg/ml obviously promotes activatory splenocyte DNA of concanavalin A, Con A (COnA) and proteinic biosynthesis, the synthetic peak of DNA 48 hours.(IL-2) produces obvious potentiation to interleukin II, and glycyrrhizic acid can strengthen CONA induction of lymphocyte secretion IL-2, and can strengthen COnA induction of lymphocyte secretion r-interferon (IFN-r), can improve splenocyte and produce IFN-r.200vb/kg increases COnA and induces 48 hours, cell concentration 1 * 10 ³/ ml is advisable, and it is main producing IFN-r.(6) prostaglandin (PGE2) is acted on: glycyrrhizic acid have dual regulation to prostate.The stomach white mice is irritated in ammonium glycyrrhizinate 100mg/kg/ day * 7 day, through ria-determination, can significantly suppress the synthetic of lung and kidney PGE2, PGF2.After glycyrrhizic acid monoammonium awarded mouse stomach 100mg/kg/ day * 5 day, its spleen PGE2 and CAMP amount significantly increase: the rat lymph-node cell was 8 * 10 ^-10Mol/L and 8 * 7 ^-7Under the mol/L glycyrrhizic acid monoammonium concentration, secretion PGM amount also significantly increases, and may be one of approach of glycyrrhizic acid para-immunity adjusting.(7) natural killer cell (NK) activity there is remarkable potentiation, immunity of organism is had important regulating action.

2, Radix Glycyrrhizae antiinflammatory action: (1) liquorice beverage extractum has remarkable antiinflammatory action, can resist that Oleum Tiglii brings out auricular concha and the glacial acetic acid lumbar injection brings out acute exudative inflammation, inflammation to chronic granulation tissue hyperplasia also has obvious inhibitory action, antiinflammatory action disappears after extracing Mus bilateral adrenal gland, illustrates that the Radix Glycyrrhizae extractum antiinflammatory action is relevant with the adrenal gland.(2) Radix Glycyrrhizae has the antiinflammatory action of Phenylbutazone and hydrocortisone sample, its antiinflammatory composition is glycyrrhizin and enoxolone, has the steroid skeleton structure, to rat Cotton Gossypii granuloma, the subcutaneous granulomatous inflammation of formaldehyde swelling of the feet etc. all has inhibitory action, and all there is inhibitory action the inflammatory reaction 1.2.3 phase.(3) enoxolone and licoflavone are to animal rat formalin edema method, and granuloma bag method is blocked boundary's Seedling sensitization Corium Mus skin tuberculin inflammatory reaction, and the obvious anti-inflammatory and anti effect is all arranged.Licoflavone has strong inhibition mice carrageenin edema and suppresses sensitive cells and discharges the chemical transmitter substance effect, the Radix Glycyrrhizae antiinflammatory action may with suppress the permeability-related of blood capillary, relevant with the effect of adrenocortical hormone sample.(4) Radix Glycyrrhizae antiinflammatory action mechanism: antiinflammatory action is relevant with the effect of adrenocortical hormone sample, in addition, Radix Glycyrrhizae reduces the formation of active oxygen by the metabolism that suppresses neutrophilic leukocyte, thereby produces antiinflammatory action, also is one of its antiinflammatory mechanism to immune effect.

3, Radix Glycyrrhizae has the effect of adrenocortical hormone sample: (1) antiinflammatory action: suppress infectious and non-infectious inflammation, alleviate hyperemia, reduce capillary permeability, inflammation-inhibiting soaks into and oozes out, and suppresses fibroblast proliferation and granulation tissue and forms.(2) immunosuppressive action: reduce histamine, the formation of 5-hydroxy tryptamine and other material and release, thereby alleviate that anaphylaxis causes hyperemia, edema, oozes out, erythra, smooth muscle spasm and primary cellular defect, suppress the transplant organ reaction, destruction has immunocompetent lymphocyte, suppresses macrophage and engulfs and handle antigenic.(3) antitoxin effect: endotoxin due to the antibacterium and extracellular toxin and various drug toxicity to the stimulation of body, are alleviated cell injury, the protection body.(4) Antishock function: remove small blood vessel spasm, strengthen the heart power that contracts, microcirculation improvement all has antagonism to toxic shock, hemorrhagic shock, cardiogenic shock, anaphylactic shock.(5) to metabolic effect: rising blood glucose and glycogen source make the albuminolysis metabolism.(6) to lymphoid tissue and blood cell effect: heavy dose can make the thymic lymphoma knot, and the atrophy of spleen inner tissue suppresses lymphadenosis, makes blood medium-sized lymphocyte, eosinopenia.Can stimulate bone marrow to make erythrocyte, neutrophil cell and thrombocytosis.

4, Radix Glycyrrhizae has calmness, analgesic, analgesia, spasmolytic, anticonvulsant action: (1) sweet subacid 1250mg/kg presents inhibitory action to the mice nervous system, calm, hypnosis time lengthening, respiration inhibition etc.(2) glycyrrhizic acid and subacid have analgesic, reduction body temperature effect to generate heat rat and mice, rabbit.(3) analgesic activity: extract Fm100 has obvious analgesic activity, and the method for measuring the threshold of pain with the method for compressing mouse tail shows that analgesic activity is arranged.And spasmolysis arranged.Have excited and the inhibition dual regulation.Anticonvulsant action.

5, to the effect of neuroreceptor: glycyrrhizic acid and enoxolone are at working concentration 8 * 10 ^-3Mol/L and 4 * 10 ^-2During mol/L, acetylcholinesterase is produced obvious inhibitory action.Drug level during its 50% suppression ratio is respectively 25.6 ± 1.4ug/ml and 21.9 ± 1.1ug/ml.These two kinds of medicinal active ingredients all are competition-non-competing type to acetylcholinesterase and mix inhibition.

6, anti AIDS virus (HIV) effect, antibacterial action: (1) glycyrrhizin 0.5mg/ml presses down 98%, 50% plaque to the propagation of HIV and forms inhibiting value 0.125, but the reverse transcription that can not suppress HIV then plays a role by recovering the T cell.(2) glycyrrhizic acid and licoflavone, the rate of increase that 0.5mg/ml suppresses HIV reaches 98%, and 3 kinds of composition suppression ratio of licoflavone are 25 times of glycyrrhizin.(3) Stomatovirus, adenovirus, vaccinia virus, herpesvirus all there is inhibitory action.(4) antibacterial action: glycyrrhizic acid and enoxolone are to golden Portugal bacterium, tubercule bacillus, escherichia coli, infusorian, ameba etc., and 6.25-12.5vg/ml is bacteria growing inhibiting fully.

7, antitumor action: (1) glycyrrhizic acid, enoxolone all have inhibitory action to rat, mouse ascites hepatocarcinoma, yoshida sarcoma, leukemia, myeloma etc.(2) antitumor principle: glycyrrhizic acid, glycyrrhizin have and strengthen nitric oxide in the mouse macrophage and produce inhibition to tumor proliferation, and cause macrophage, and lipopolysaccharide (LPS) stimulates the generation nitric oxide, suppresses tumor proliferation.

8, Radix Glycyrrhizae complex (LX) Detoxication: the heart, liver, kidney, endocrine, reproductive system are all had protection and Detoxication; various toxin and drug-induced arrhythmia have protective effect; contractility is strengthened; to liver, the injury of kidney due to various medicines and the toxin; the reproductive system infringement has protective effect, anti-injury effect.

9, to the reproductive system effect: (1) glycyrrhizin, enoxolone low dose of can inhibitory hormone to the accretion of teenage animal uterus, testis, adrenalectomize or ovary, testis still have same purpose later on.(2) when glycyrrhizin dosage increases, the then anti-estrogen-like effects that strengthens.Enoxolone 10vg/ml can suppress the 17-B-hydroxysteroid dehydrogenase, and to change androstanedione be the effect of testosterone, is suppressed gathering of the 17-a-flavonol that causes owing to above-mentioned enzyme, and therefore, the enoxolone heavy dose has the mouse propagation of inhibition gland generation testosterone effect.(3) Radix Glycyrrhizae has dual regulation according to dosage to man, female reproductive system system.

10, Radix Glycyrrhizae Detoxication mechanism: (1) with its sweet in the mouth can and, be in harmonious proportion the property of medicine with detoxifcation.(2) with its sweet in the mouth can delay, relax high suddenly with the detoxifcation.(3) with its sweet in the mouth can mend, strengthening the body resistance with the detoxifcation.(4) cool in nature with it with heat-clearing and toxic substances removing.(5) modern study Radix Glycyrrhizae detoxifcation mechanism: enoxolone and poisonous substance combination make it be converted into the less or avirulence material of toxicity.Glycyrrhizin absorption poisonous substance is with detoxifcation, and its detoxifcation and adsorption rate are proportional.Glucuronic acid can combine with the noxious substance of some hydroxyls or carboxyl in the body after dehydration and become non-toxic compound by the urine discharge.The adrenocortical hormone sample effect of glycyrrhizic acid and enoxolone, similar glucuronic acid in conjunction with Detoxication, with regulating action of improving hypophysis-adrenal system etc., glycyrrhizic acid has the detoxifcation potentiation.

11, to antioxidation and anti-aging effects: licoflavone class and Saponin all have antioxidation and anti-aging effects.

12, pharmacokinetics: the oral small intestinal absorption experiment of (1) glycyrrhizic acid proves: glycyrrhizic acid is one-level in little intestinal absorption and absorbs.Oral administration is given rat 500mg/kg glycyrrhizic acid, and with the blood drug level of ammonium glycyrrhizinate in the HPLC mensuration blood plasma and glycoside unit enoxolone thereof, 30 minutes as a result peakings are about 30vg/ml, survey after 4 hours just to reach the peak, and medicine is 15vg/ml.Decay to 10vg/ml after 8 hours, from blood, disappear after 20 hours.The oral 100mg Radix Glycyrrhizae of normal person acid amide shows that with immunization mensuration two peaks appearred in enoxolone concentration in the blood after administration 1-4 hour and 10-24 hour, and peak value is about 500vg/ml.(2) absorption of glycyrrhizic acid intravenously administrable: quiet notes 50,20mg/kg measures blood sample with the HPLC method, and the result shows, and glycyrrhizic acid is by descending rapidly in 30 minutes at blood concentration, just slowly keeps Reduction Level in 60 minutes.If give the quiet notes ammonium glycyrrhizinate of hepatic injury patient 80mg, detect enoxolone concentration in the blood plasma with method, in the bleeding from anus enoxolone appearred at 6 hours, reach the peak after 24 hours, be about 7mg/ml, the hepatic injury patient is lower than this level.(3) quiet notes glycyrrhizic acid is most of combines with plasma protein, and a part is distributed to liver rapidly, more slowly is distributed to other organs and tissues on a small quantity.

13, toxic and side effects: (1) liquorice beverage extractum acute toxicity, the quiet notes of mice LD ₅₀Be 1.94320 ± 0.467g/kg, lumbar injection LD ₅₀Be 6.8466g/kg, subcutaneous notes LD ₅₀Be 7.8192g/kg.Radix Glycyrrhizae extractum LD100 is 3.6g/kg, and the cause of the death is paralysis.(2) the subcutaneous notes of glycyrrhizic acid mice MLD is 1g/kg, enoxolone mouse peritoneal injection LD ₅₀Be 308mg/kg, dead animal is seen peritonitis, injects medicine and does not absorb fully.Carbenoxolone Sodium acid half ester mouse peritoneal injection LD ₅₀Be 101mg/kg, quiet notes are 43mg/kg.Radix Glycyrrhizae methanolic extract Fm100 mouse peritoneal injection LD ₅₀Be 760mg/kg.Enoxolone has the Cavia porcellus of inhibition thyroid function, and the trend that reduces basal metabolism is arranged.(3) long term toxicity: Radix Glycyrrhizae extractum 1g every day gavages 40 days to rabbit, and the administration group increases to some extent than matched group body weight, and all blood sodium obviously rises after the administration, and is constant after a week, adrenal gland's underactivity, and atrophy is arranged slightly.Radix Glycyrrhizae extractum 2g/kg every day gavaged in continuous 40 days, and result and matched group comparison body weight have increase (but non-edema causes) slightly, did not have deadly in the experiment, checked that each organ weights sees that adrenal gland's weight reduces, and the rarely seen glomerule of tissue examination is some unusual.Glycyrrhizin heavy dose (20-30mg/kg is more than the continuous week) can cause edema, but both can disappear after the drug withdrawal.Heavy dose of enoxolone 125mg/kg absorbs mice and suppresses weight loss.

(3) Radix Tripterygii Wilfordii extract tripterygium glycosides pharmacological action:

1, to antiinflammatory action: tripterygium glycosides can suppress that capillary permeability increases due to the mice dimethylbenzene histamine etc., suppresses rat Oleum Tiglii and granuloma induced by implantation of cotton pellets, suppresses Ovum Gallus domesticus album and formaldehyde foot swelling.Tripterygium glycosides has stronger antiinflammatory and analgesic activity, its analgesic effect with anti-inflammatory is caused the pain medium relevant.Radix Tripterygii Wilfordii has strong antiinflammatory and analgesic activity, and similar ACTH sample effect is arranged.

2, the Radix Tripterygii Wilfordii glycoside has excitation to hypothalamus-hypophysis-hypothalamic pituitary adrenal axis: excited hypothalamus and impel the secretion of adrenal cortex releasing hormone (CRH) to increase, or optionally excited suprapituitary crh receptor, and act on the adrenal gland indirectly.Radix Tripterygii Wilfordii is controlled autoimmune diseasees such as rheumatoid arthritis, except that strong immunosuppressive action, and strong excited hypothalamus-hypophysis-hypothalamic pituitary adrenal axis is arranged, and the secretion 17-hydroxy-11-dehydrocorticosterone strengthens antiinflammatory action.Many glycosides can suppress the effect of PGE2, and its effect is weaker than antifan slightly, is better than dexamethasone, is the antiinflammatory action of Radix Tripterygii Wilfordii.

3, Tripterygium glycosides is to the immune system effect: (1) Radix Tripterygii Wilfordii is the strong inhibitor of cellular immunization and humoral immunization: tripterygium glycosides 60mg/kg, can make young Mus atrophy of thymus gland, and long term administration makes the adult rats atrophy of thymus gland, but can not influence the spleen loss of weight.Radix Tripterygii Wilfordii is drenched cell immune responses such as commentaries on classics and MLC in vitro to phagocytic function, truly has the significant inhibitory action relevant with drug dose.Interleukin-1 (IL-1) has the thymus of impelling proliferation function, Radix Tripterygii Wilfordii adds the inductive thymocyte proliferation reaction of reduction IL-1, administration 5-8 days, not only cause atrophy of thymus gland, thymus reduces the reactivity of L-1, also causes splenocyte that the inductive T cell proliferative response of concanavalin A, Con A (COnA) is weakened.Many glycosides have anti-graft versus host disease (GVHD) effect: mouse bone marrow cells is transplanted the back and is given Tripterygium glycosides 12.50mg/kg.d logotype 7d, the 18.5d of on average surviving; With many glycoside survival 11.7d, Radix Tripterygii Wilfordii can the inhibition of transplant rejection reaction for matched group.Utilize local xenogenic graft versus host reaction (GVHR); The allo-skin graft reaction, external hemolytic reaction, four kinds of methods such as primary immune response studies show that: Tripterygium glycosides is the inhibitor of a kind of cellular immunization and humoral immunization.(2) Tripterygium glycosides produces inhibitory action to delayed hypersensitivity and IL-2: 12mg/kg administration every day significantly suppressed Cavia porcellus old tuberculin delayed hypersensitivity after 11 days, and suppressor T cell propagation and E Flos Rosae Rugosae (garland and active ring) reaction.But suppressor T cell enters the S phase from G0/G1, and the IL-2 of suppressor T cell produces.(3) Tripterygium glycosides has the inductive autoimmune response of the campylobacter jejuni of inhibition, and the ds-DNA autoantibody of rising can be suppressed by Tripterygium glycosides, makes the TH/TS ratio restitution of rising, and the hyperfunction T of infected mice, B cell function are all had inhibitory action.(4) tripterygium glycosides can suppress the specific antibody generation of the anti-sheep red blood cell (SRBC) of antigen binding cell and antibody secreting cell, the synthetic positive feedback approach of 1gG antibody in the blocking-up patient with rheumatoid arthritis body, and disease is eased.Also can make humoral immune reaction trend hyperfunction in the body normal, the clinical total obvious effective rate 85.3% of rheumatoid arthritis is treated back patients serum 1gG, 1gM, 1gA, is all reduced.Rheumatoid factor (RF) titre lowers or turns out cloudy, and illustrates that Radix Tripterygii Wilfordii truly has strong inhibition antibody nucleus formation.(5) tripterygium glycosides (T1) is to IL-2 and IL-2R genetic transcription, experiment with the dot blot hybridization method from IL-2T and IL-2RP55 gene transcription level inhibitory action to tripterygium glycosides (T1), done further research, observing T1 is to suppress PHA to induce down transcribing of cell IL-2mRNA and IL-2RP55mRNA, and it is the strongest that inhibitory action is induced to the 12nd hour end at PHA.TI is to CD ⁴⁺Cell and CD ⁸⁺Cell all has obvious inhibitory action, to CD ⁴⁺Cyto-inhibition is stronger.(6) Tripterygium glycosides is to human lymphocyte IL-2 autocrine loop inhibitory action: many glycosides are to t cell activation, the generation of IL-2, and the expression of IL-2R and activating T cell be to the reactivity of IL-2, and disturb the signal transducting system of IL-2 that inhibitory action is all arranged.

4, Tripterygium glycosides has inhibitory action to motility of sperm, sperm count, sperm concentration: (1) male mice clothes Tripterygium glycosides 20-30mg/kg; 1-3 month; the cauda epididymis motility of sperm reduces, sperm count, and sperm concentration significantly descends; and different in nature sperm count obviously raises; the testis loss of weight, forfeiture fertility, drug withdrawal 2-3 month; fertility both can also not have effect to the offspring genitals near normally or fully recovering normal.(2) Radix Tripterygii Wilfordii has inhibitory action to the male reproductive organ structure: Mus clothes Radix Tripterygii Wilfordii glycoside 30mg/kg/ day great and mighty or powerful, obeyed 35 days, can cause the sexual cell damage when total amount reaches 1.05g/kg: motility of sperm significantly reduces, testicular sperm cell and spermatogenesis are obviously changed in quality or are reduced, and the minority spermatocyte pathological changes occurs and sloughs off.Took medicine 80 days, when total amount reached 2.4g/kg, then damage increased the weight of, sperm in the convoluted seminiferous tubule, and spermatid and spermatocyte come off, degenerate, disappear, and involve the part spermatogonium.The testis loss of weight is over half, and residual sperm all is out of shape, and mainly is spermatogenic cell to the target cell of reproductive system, and its damage is relevant for a long time with dosage and time.Obey behind many glycosides that lactate dehydrogenase isoenzyme (LDH-C4) content descends in the testis.

5, Tripterygium glycosides is to the antifertility of jenny: (1) mice clothes 30mg/kg/ day Radix Tripterygii Wilfordii 35-84 days altogether, sexual cycle is irregular by normally transferring to, imperfect or the prolongation of sexual activity cycle, the uterus loss of weight, the attenuation that attenuates of part uterus smooth muscle fiber, the endometrial gland organelle obviously reduces, and lysosome increases, still visible edge follicle of ovary and degeneration corpus luteum prove that animal has the ovulation phenomenon.(2) to the influence of estrogen: estrogen has three kinds of each estradiol, estriol and estrone etc.: the activity of estradiol (E2) is the highest.Follicular development under follicle stimulating hormone (FSH) stimulates, and under metakentrin (LH) is collaborative, promote the granule of follicle to accelerate to discharge estrogen such as E2.When ovarian function failed or suppressed, estrogen secretion will reduce.When (3) Radix Tripterygii Wilfordii was controlled women's rheumatoid arthritis, when accumulation surpassed 8000mg, amenorrhea took place in the eumenorrhea person before 95% treatment.Serum E2, FSH, LH content are normal before the treatment, and E2 descends after the medication; FSH, LH all raise.Illustrate that Radix Tripterygii Wilfordii by ovarian function is suppressed, secretes the E2 minimizing and causes amenorrhea.

6, Tripterygium glycosides suppresses antibody and immunocomplex formation: (1) Tripterygium glycosides stops immunocomplex to form the effect that also is deposited in the glomerule.Around the 15mg/kg clothes, urine protein obviously descends, and the plate-like protein electrophoresis turns to middle molecule protein, plasma protein, creatinine all to recover normal from macromole.(2) Tripterygium glycosides can significantly reduce Glomerulonephritis Rats urine protein, serum MDA renal cortex MDA such as gentle red piece of element, Ma Shan and can significantly reduce the Glomerulonephritis Rats allosome mutually with from the urine protein of bulk phase, serum MDA and renal cortex MDA, the nephridial tissue that obviously alleviates from bulk phase changes, but does not act on the deposition of electron-dense thing in glomerular basement membrane.Multiple nephritis model there are prevention and protective effect.

7, Tripterygium glycosides is to the adrenal cortex function effect: Tripterygium glycosides has the adrenal cortex reinforcing function, and glucocorticoid is synthetic in vivo, and secretion and metabolic result have caused urinating in the body variation of-17 hydroxysteroid content.Hypothalamus-hypophysis-interrenal system is had potentiation, and many glycosides can be blocked histamine, and 5-hydroxy tryptamine is to the effect of the intestinal that exsomatizes, but Vitamin C content in the rat adrenal gland is not had effect.The not excited or low bad hypophysis-interrenal system of antiinflammatory action of Tripterygium glycosides is described.Curative effect to autoimmune diseasees such as rheumatoid arthritiss is relevant with his immunosuppressive action.

8, Radix Tripterygii Wilfordii is to the metabolic effect of body protein: (1) globulin is that reticuloendothelial cell and plasma cell produce.More antibody is the r globulin in the human plasma, and blood plasma 1g is exactly the globulin that has the antibody effect in the blood plasma, measures the r globulin of rheumatoid arthritis patients, obviously increases 20% before the treatment, treats obviously reduction or multiple normal after month.(2) Tripterygium glycosides is controlled rheumatoid arthritis, anemia patient before controlling, and the treatment back is most recovers normal.

9, Tripterygium glycosides is to the cardiovascular effect: (1) function of promoting blood circulation to disperse blood clots: remove the blood aggregation, reduce viscosity of blood, the fibrinolytic obstacle is corrected in anticoagulant, and microcirculation improvement reduces the PBF drag effect.(2) atrium of leaving one's post there is excitation, irregular to the property a crossed heartbeat occurs at systemic heart.Hypotensive effect is arranged, and the range of decrease is relevant with dosage, and small artery diastole on every side and blood flow are increased, to breathing and shrinking obviously influence of nothing every flesh.

10, resisting pathogenic microbes effect: (1) Radix Tripterygii Wilfordii is a broad spectrum antibiotic, and Gram-positive, negative bacteria etc. are all had inhibitory action for 48 kinds, and is good especially to the Candida albicans effect, and many glycosides have certain inhibitory action to golden Portugal bacterium, bacillus subtilis etc.(2) antivirus action: separate that to obtain a kind of Kaurane diterpine lactone Radix Tripterygii Wilfordii good fortune fixed, very strong anti-AIDS cytotoxic activity is arranged, its anti human immune deficiency virus (HIV) duplicates in the H9 lymphocyte active EC ₅₀Be 1g/ml.

11, to the sliding flesh effect of central nervous system's peace: Radix Tripterygii Wilfordii can cause that the severe malnutrition of Thalamus, midbrain, medulla oblongata, cerebellum and spinal cord sexually revises, and may be that the unselected cell toxic action is relevant.Excited smooth muscle effect is obvious, exsomatizes or all has contractility to strengthen in the body uterus, and ileum is also had excitation.

12, antitumor action: triptolide 0.1-0.2mg/kg is effective to mouse leukemia L1210 and P388, and breast carcinoma and gastric cancer are all had strong curative effect, and effectively suppression ratio all has obvious inhibitory action to murine sarcoma S37, hepatocarcinoma etc. more than 70%.

13, pharmacokinetics: the oral or quiet notes of Radix Tripterygii Wilfordii, medicine extensively distributes in vivo, and organizes affinity strong, is distributed as the liver＞spleen＞lung＞intestinal＞heart＞brain at bulk concentration, plasma protein is in conjunction with 64.7%, irritate the quiet notes of harmonization of the stomach, disappear in vivo half time of medicine is 2 days, all excretes after 12 days, by discharging in excrement and the urine, be the part metabolite of advocating peace with former medicine, the medicine bile excretion is 6.73% in 24 hours, and the liver sausage circulation is arranged in vivo.

14, toxic and side effects: (1) chmice acute LD ₅₀For: the complete oral 18.4-26.55g of root decoct, lumbar injection 4.8g/kg, the oral LD of many glycosides ₅₀Be 159.70mg/kg, toxicity took place at 24-60 hour.Many glycosides lumbar injection LD ₅₀Be 93.99mg/kg, poison and took place at 12-48 hour.(2) main toxicity: 1. intestinal and gastric mucosa are produced slight gangrenous inflammation, cause hyperemesis, suffer from diarrhoea, have blood in stool etc.2. electron microscopic observation is found, the formation of the multiple molten kitchen range of cardiac muscle damages cardiac muscle.3. toxic dose makes the extensive disintegrate of lymphocyte of spleen and causes immunologic function degression, the atrophy of splenic nodule joint.4. renal tubular cell distortion and downright bad is relevant with renal failure.5. extensive gastrointestinal is seen in the death postmortem of Zhong Duing, hemorrhage, the liver pulmonary congestion of cardiac muscle, renal tubular necrosis, and the big person of dosage has cardiac damage, acute cardiac anencephalohemia and malign lung edema.

The invention will be further described below in conjunction with embodiment.

The capsular prescription of this Herba mesonae chinensis rattan consists of Herba Epimedii, Radix Glycyrrhizae, Radix Tripterygii Wilfordii.

Preparation method is realized by following processing step:

(1) Herba Epimedii extraction process:

(2) extraction process of Glycyrrhiza uralensis:

(2) pure product glycyrrhizic acid extraction process: the thick glycyrrhizic acid 400g of above gained adds 4 times of amount ethanol, reflux 3 hours, filter, filtering residue adds 2 times of amount alcohol refluxs 2 times, merges backflow, adds the 10g active carbon, reflux decolour cooling half an hour, filtration, the logical ammonia of filtrate is to PH7-7.5, and till no solid was separated out, filtrate was precipitated, with small amount of ethanol washing, drying at room temperature, get ammonium glycyrrhizinate 250g;

(3) tripterygium glycosides extraction process:

(4) Herba mesonae chinensis liana rubber capsule preparation technology: use according to clinical repetition test and checking, select the best safety consumption: icariine 50mg/kg/ day, epimedium flavone 20mg/kg/ day, epimedium brevicornum polysaccharide 20mg/kg/ day; Glycyrrhizic acid 50mg/kg/ day, licoflavone 10mg/kg/ day, Radix Tripterygii Wilfordii glycoside 1.5mg/kg/ day; All calculate consumption, amount to 7575mg/50kg/ day, be divided into and adorn 16 large size capsules, each capsule dress 473.43mg by 50 body weight.

Claims

1, a kind of Herba mesonae chinensis liana rubber capsule is characterized in that prescription consists of Herba Epimedii, Radix Glycyrrhizae, Radix Tripterygii Wilfordii, and extract constitutes: icariine 33%, epimedium flavone 14.5%, epimedium brevicornum polysaccharide 14.5%; Glycyrrhizic acid 33%, licoflavone 6.6%, Radix Tripterygii Wilfordii glycoside 0.99%.

2, the capsular preparation method of a kind of Herba mesonae chinensis rattan is characterized in that being realized by following processing step:

(1) Herba Epimedii extraction process:

(2) the pure product extraction process of Herba Epimedii Saponin: Herba Epimedii crude product extractum adds 70%4 times of amount ethanol, and heating cocurrent flow 2 hours filters, and filtering residue adds 2 times of amount alcohol refluxs 1 hour again, filters, and reclaims ethanol, 60 ℃ of dryings;

(3) epimedium brevicornum polysaccharide extraction process: Herba Epimedii is pulverized coarse powder and is added 5 times of amounts of 75% ethanol 0.5NHaoH reflux 2 hours, filters, and extracts three times with method, merging filtrate is condensed into cream, add 95% ethanol with being stirred to precipitation, spending the night, filtering, reclaim ethanol, continuous 2 times; Add 2 times of amounts of water,, get pure product epimedium brevicornum polysaccharide with phosphate type DEAE cellulose chromatography purification;

(2) extraction process of Glycyrrhiza uralensis:

(3) tripterygium glycosides extraction process:

(1) the Radix Tripterygii Wilfordii coarse powder is measured reflux, extract, for 5 times with 85% methanol, filtered while hot, and medicinal residues add fresh solvent again, and reflux, extract, is 3 times repeatedly, and each 4 hours, merge 4 times methanol extract liquid, reclaim methanol, concentrating under reduced pressure promptly gets thick general glycoside extractum;

(2) thick Saponin extractum is dissolved in water, and the back is chloroform-methanol-n-butyl alcohol-water with D.C.C-A type droplet countercurrent chromatography solvent system, and volume ratio was by 45: 60: 6: 40, lower floor's phase that fixes, mobile phase is made on the upper strata, and stripping solution is collected with collecting instrument automatically step by step, reclaims solvent; N-butanol extracting liquid, washing back concentrating under reduced pressure promptly gets the genuine soap glycoside;