CN1105564C

CN1105564C - Medicine for warming kidney and treating wind-dampness syndrome and preparation process thereof

Info

Publication number: CN1105564C
Application number: CN00121849A
Authority: CN
Inventors: 辛耀禄
Original assignee: Individual
Current assignee: Individual
Priority date: 2000-07-25
Filing date: 2000-07-25
Publication date: 2003-04-16
Anticipated expiration: 2020-07-25
Also published as: CN1285201A

Abstract

The present invention provides a medicine for warming the kidney and treating wind-dampness syndrome and a preparing technology thereof. The medicine is prepared from epimedium brevicornum glycoside selenium, epimedium polysaccharide, zinc glycyrrhizate, liquorice flavonoids, sophora alopecuroides total base manganese, hyoscyamine and aconine. The medicine is mainly used for treating rheumatic arthralgia (rheumatic arthritis), rheumatism (rheumatoid arthritis), rheumatism involving the bone (ankylosing spondylitis, hyperosteogeny, retrograde osteoarticular lesion and hypertrophic osteoarthropathy), etc. The preparation of the present invention is reasonable, and the extraction technology is advanced. The present invention adopts unprecedented in vivo essential trace elements to be used as solvent, and adopts the control of acid, alkali and temperature; the toxic medicines are hydrolyzed into nontoxic medicine at high temperature, and the medicine has the advantages of good therapeutic effect, few toxic side effect, wide medicinal resource and low price.

Description

The kidney warming rheumatism medicine and preparation technology thereof,

Technical field

The present invention relates to treat the medicine of rheumatism, especially the kidney warming rheumatism medicine and preparation technology thereof.

Background technology

Rheumatism numbness (rheumatic arthritis), In-particular king's numbness (rheumatoid arthritis), rheumatism involving the bone diseases such as (ankylosing spondylitis, hyperosteogeny, degenerative osteoarthropathy, hypertrophy bone change), the treatment difficulty is big, and the expense height gets this type of disease, the patient suffering, but have no way out.At present, do not have also that a kind of curative effect is high especially, toxic and side effects is little, the medicine source wide, cheap specific drug.

Summary of the invention

The purpose of this invention is to provide a kind of reasonable recipe, extraction process advanced person, adopt and to tie up secondary element in the unprecedented body and make solvent, acid, alkali, temperature control, the toxic medicament pyrohydrolysis becomes nontoxic efficient good medicine, curative effect is high especially, toxic and side effects is little, the medicine source is wide, cheap the kidney warming rheumatism medicine and preparation technology thereof.

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

A kind of the kidney warming rheumatism medicine, its prescription consists of icariine selenium, epimedium brevicornum polysaccharide, zinc glycyrrhetate, licoflavone, the total alkali manganese of Herba Sophorae alopecuroidis, hyoscyami alkali, aconine.

The preparation technology of aforementioned the kidney warming rheumatism medicine is specially:

(1) icariine selenium, the epimedium brevicornum polysaccharide extraction process:

(1), crude product icariine selenium extraction process, the former medicine of rough lumber adds 8 times of amount 1% selenic acid liquid, kept 80 ℃ of reflux, extract, 3 hours, filtering the extraction medicinal liquid puts in addition, residue adds 5 times of amount 1% selenic acid liquid again, presses the Same Way operation and extracts 2 hours, and medicinal liquid is extracted in multiple filter and preceding liquid merges, gather all selenic acid extracting solution, be 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 with 45% washing with alcohol 2-3 time, and the solubility composition washes out in will precipitating, filtrate and washing liquid merge, and reclaim ethanol, concentrating under reduced pressure is cooled to cream, has both got the thick extracted extract of Herba Epimedii selenium;

(2), pure product icariine selenium extraction process: the thick extracted extract of Herba Epimedii selenium adds 70%4 times of amount ethanol, and heating and refluxing extraction 2 hours is filtered, and filtering residue adds 2 times of amount alcohol reflux 1 hour again, filters, and reclaims ethanol, 60 ℃ of dryings, both pure product Herba Epimedii selenium;

(3), epimedium brevicornum polysaccharide selenium extraction process: Herba Epimedii is pulverized coarse powder and is added 5 times of amounts of 75% ethanol, 0.5% sodium selenate (Na ₂SeO ₄) heating and refluxing extraction 2 hours, filter, extract 3 times with method, merging filtrate is condensed into cream, add 95% ethanol with being stirred to precipitation, 12 hours after-filtration reclaim ethanol, continuous 2 times, add 2 times of amounts of water,, get pure product epimedium brevicornum polysaccharide selenium with DEAE cellulose (phosphate type) column chromatography purification;

(2) aconine extraction process:

The Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) coarse powder after 48 hours, was heated 2 hours 40 ℃ of percolation with 6 times of amounts of 1% hydrochloric acid, 70% ethanol warm macerating with 15 pounds of pressure; Secondary, all use for three times with the method percolation, merge three percolates and filter, filtrate is reclaimed ethanol to there not being the alcohol flavor in water-bath, and the logical dense ammonia of filtrate is condensed into cream to pH value 7-7.5 precipitation filtrate, and 15 pounds of pressure of reuse steamed after 2 hours, were dried into powder, both got aconine;

(3) Radix Physochlainae is extracted hyoscyami alkali: get Radix Physochlainae coarse powder 1000g, soak after 48 hours by seepage method seepage continuous 3 collection effusion 10000ml with 70% ethanol, reclaim ethanol and be concentrated into 500ml, put separatory funnel defat with petroleum ether 2 times, divide water intaking liquid, steam and remove unrecovered oil ether; Add strong aqua ammonia and regulate PH10-11, gradation 250ml, 200ml, the biological alkali of 150ml chloroform extraction; Combined chloroform liquid, gradation is carried most biological alkali with 2% hydrochloric acid 200ml and 1% hydrochloric acid 300ml, 200ml, 100ml; Merge acid extraction liquid, add strong aqua ammonia and transfer PH10-11, gradation is carried most biological alkali with chloroform 300ml, 200ml, 100ml; Combined chloroform liquid is carried most biological alkali with 1% hydrochloric acid 200ml and 0.5% hydrochloric acid 200ml, 100ml respectively, merges sour extract, transfers PH2-3, and heating in water bath is removed residual chloroform, adds 0.2% decolorizing with activated carbon, filters, is condensed into crystallization;

(4) Herba Sophorae alopecuroidis alkali manganese extraction process:

(1), extraction process: Herba Sophorae alopecuroidis or root pulverize to coarse powder, add 5 times of amounts of 1% manganese sulfate, 75% ethanol reflux inclined and supernatant in 1 hour; The same method of medicinal residues adds 70% ethanol, 1% manganese sulfate heating and refluxing extraction 2 times again, merges 3 times extracting solution, quiet amount 1-2 days, filter, filtrate recycling ethanol, to do not have the alcohol flavor, be condensed into cream, the oven dry back becomes dry extract standby;

(5) Radix Glycyrrhizae is extracted zinc glycyrrhetate:

(1), thick zinc glycyrrhetate extraction process: thick Radix Glycyrrhizae powder is measured 0.5% zinc carbonate (ZnCO with 12 times ₃) soak seepage after 12 hours, continuous 3 times, effusion is concentrated into original volume 1/5 and filters, filtrate adds concentrated sulphuric acid to PH3, filters the precipitation of separating out, wash 3 times, drying below 60 ℃, both thick zinc glycyrrhetate;

(2), pure product zinc glycyrrhetate extraction process: above gained zinc glycyrrhizate 400g, add 4 times of amount ethanol, reflux 3 hours, filter, filtering residue adds 2 times of amount alcohol heating reflux 2 times, merges all backflow and adds the 10g active carbon, reflux decolour cooling half an hour, filter, filtrate ammonification controlled atmosphere is to PH7-7.5, till no solid is separated out; The filtrate precipitation, with the small amount of ethanol washing, drying at room temperature gets zinc glycyrrhetate 250g;

(3), glycyrrhiza residue and precipitate extract zinc glycyrrhetate, licoflavone: Radix Glycyrrhizae residue and precipitate add 1% zinc sulfate (ZnSO ₄) and 70% ethanol be lyase, hot dipping 8 hours, reflux 2 hours is filtered, continuous 2 times, merging filtrate reclaims ethanol, is condensed into cream, has both reclaimed zinc glycyrrhetate, licoflavone;

(6), preparation process: get the icariine selenium 50mg/kg/ day for preparing; Epimedium flavone 10mg/kg/ day; Epimedium brevicornum polysaccharide 10mg/kg/ day; Zinc glycyrrhetate 40mg/kg/ day; Licoflavone 10mg/kg/ day; The total alkali manganese of Herba Sophorae alopecuroidis 10mg/kg/ day; Hyoscyami alkali 0.41/kg/ day; Aconine 0.1mg/kg/ day, press the 50kg body weight per capita and calculate consumption, amount to 6525.5mg/50kg/ day, 14 capsules of packing, each capsule contains 466mg.

The present invention has following pharmacological action and effect thereof:

One, the kidney warming rheumatism Drug Capsule medicine characteristics:

1, we have novelty, reasonable recipe: be made up of Herba Epimedii, Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani), Radix Physochlainae, Herba Sophorae alopecuroidis, Radix Glycyrrhizae.Have efficient, quick-acting, low toxicity, the minimum characteristics of side effect.We have very strong kidney invigorating and YANG supporting, bone and muscle strengthening, benefit smart, mend the waist knee joint, blood circulation promoting and blood stasis dispelling dispel the wind dampness removing, dispelling cold by warming the meridian, to prolongedly do not heal, the disease of phlegm and blood stasis, 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 strong shape, and very strong immunological enhancement arranged, especially to rheumatic arthritis, that rheumatoid arthritis, ankylosing spondylitis really reach is efficient, quick-acting, low toxicity, unique, very strong anti-inflammatory analgetic, detumescence excellent results.(1) efficient: according to 446 routine rheumatism numbness (rheumatic arthritis) clinical treatment observations: as to take " the kidney warming rheumatism Drug Capsule ".Cure 382 people and account for 85.65%; Produce effects 35 people account for 7.85%; Effective 22 people account for 4.93%; Total effective rate 98.43%.(2) quick-acting: the people who takes the kidney warming rheumatism Drug Capsule 3-7 day 93.45% can reach pain relieving, and the detumescence rate reaches 85.65% in 7 days.(3) low toxicity: clinical treatment In-particular numbness (rheumatoid arthritis) rheumatism involving the bone (ankylosing spondylitis, hyperosteogeny) was taken 1-3 month, and after testing: the heart, liver, kidney, the reproductive system organ pipe is all harmless.Groups of people serve on 6 months or are interrupted to take and did not see the heart, liver, kidney, reproduction and hemopoietic system infringement through biochemistry detection in 1 year.Just groups of people have gastrointestinal reaction, formerly have the inclination, liver, nephropathy change person, and one or two people respond.People to reproduction 1% responds or the hyposexuality phenomenon, and one or two people have cacospermia.All women do not have amenorrhea or uterus ovary loss of weight phenomenon etc., illustrate that toxicity is extremely low.

2, this side's medicine extraction process advanced person, purity height are so poison pair effect is little: compare and curative effect raising 300% with similar medicine.Particularly the last skill Artemisia of snow is used high temperature, high pressure, dimension secondary element, acid, alkali, temperature control novel technology for extracting.Biological alkali (acetyl benzaconine, mesaconitine, inferior acetyl benzaconine, jesaconitine, the delphisine) toxicity of two fat type Diterpeneses is very big) become the biological alkali of monoesters class (stupid formyl aconine is Aconitum carmichjaelii Debx. time alkali, stupid formyl mesaconitine both, stupid formyl time acetyl benzaconine) toxicity less (being the toxic 1/500-1/1000 of the biological alkali of di esters) through the High Temperature High Pressure acidic hydrolysis.Become biological alkali (aconine is aconine, mesaconitine, hypo-aconine both) the toxicity minimum of alcamines through the High Temperature High Pressure acidic hydrolysis again, (toxicity is two lipids alkaloidal 1/2000) is so toxicity is extremely low, clinical practice is very safe, and the effect of rheumatism stopping numbness pain is better than salicylic acid inferior to morphine.Wind-damp dispelling antiinflammatory action and nonsteroidal are suitable.The analgesic effect of the biological alkali 0.1mg/kg of Aconitum carmichjaelii Debx. is also strong than morphine 6mg/kg effect.

3, kidney invigorating and YANG supporting, bone and muscle strengthening, elimination inflammation of bone, promote osteogenesis: this medicine can promote sexual function: after, seminal vesicle hyperfunction owing to the promotion gonepoiesis is full of, sensation nerve, indirect excitation libido and cause, can increase the prostate seminal vesicle, levator ani weight, promote testis and epididymis to grow sexual function improving.Strengthen women uterus, ovary weight, postponement climacteric.Anti-aging effects: prolong normal cell survival, anti-hypoxia, resisting fatigue.Eliminate sclerotin and arthritis, promote osteogenesis and rheumatism.

4, strong immunosuppressant and antiinflammatory action: suppress immunoreation, again immunological enhancement arranged.Humoral immunization, immunization of cell, dual regulation are arranged.Can induce r-interferon (1FN-r), interleukin II (1L-2), interleukin (1L-3), Z tumor necrosis factor (TNF-Z), B-transforming factor (TGF-B ₁), HIV-1 inhibitive factor, natural killer cell (NK cell).These immunologic active materials, to regulating immunity, suppress tumor, suppressing HIV remarkable effect is arranged.Treatment to connective tissue disease and immune disease has obtained effect unique especially.A variety of causes is caused that the granuloma hypertrophy has inhibitory action, reduce histamine, capillary permeability, increase the phagocytic function of inflammation emigrated cell, have very strong anti-inflammatory properties.

5, we have very strong Detoxication: among this side, the good henbane alkali of the biological alkali of Radix Physochlainae extract, atropic category, can remove Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) to the direct infringement of cardiac muscle and cardiac dysfunction, rhythm abnormality etc.Radix Glycyrrhizae is extracted glycyrrhizic acid also can remove Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) to the infringement of important organs such as the heart, liver, kidney, brain, heart is had protective effect and Detoxication, and can remove the acetyl benzaconine class endocrine reproductive system is encroached on.Glycyrrhizic acid and Herba Epimedii have dual regulation according to dosage to man, female reproductive system system.

6, we have very strong antibiotic, antifungal, antivirus action: can suppress golden Portugal bacterium, streptococcus, fungus and virus, high concentration has killing action.HIV there is very strong inhibitory action, and can suppresses hiv reverse transcriptase.To the microbial rheumatic fever of hammer, bring down a fever, pain relieving, detumescence effect extra-heavy.

7, the effect of expansion artery and vein is arranged, blood pressure lowering, heart tonifying diuresis are arranged: and the energy anticoagulant, thrombosis prevented and treated.Low dosage has good cardiotonic, antiarrhythmic effect.

8, the cell of enhancing hypoxia-bearing capability is arranged: prolong the normal cell survival time-to-live, promote protein and nucleic acid metabolism, promote the normal bone growth, prevent and treat osteitis, hyperosteogeny, degenerative osteoarthropathy takes place and development, and can prevent and treat immunoreation and cause osteitis and osteonecrosis.

9, former wide, the cheap and curative effect height of this medicine medicine, toxic and side effects little, be convenient to promote the use of: because this medicine has above such innovation novel technology for extracting; reasonable formula; so advantages such as high-efficiency low-toxicity are applied for a patent and are protected; enlarge our production scale; had more product, for Chinese people and the people of the world's hygiene and health cause are done contribution more.

Two, the kidney warming rheumatism Drug Capsule pharmacological action:

1. endocrine function is had and promote 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. we have potentiation to immunologic function: to kidney deficiency human T-cell number, pouring rate of rotation, antibody, antigen and reticuloendothelial system phagocytic hypofunction person, the every index in clothes " the kidney warming rheumatism Drug Capsule " back is improved, Histological change and minimizing extracellular matrix to kidney produce, and immunity of organism is had facilitation.Low concentration can increase 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.

3. immunoglobulin is influenced: immunoglobulin (lg) has harmful substances invasion and attack such as antagonism alien bacteria, virus, various toxin, keeps biological self stability and various important function such as immune surveillance.The patient measures its value under normal value at take medicine preceding lgG, lgA, and clothes " the kidney warming rheumatism Drug Capsule " back lgG, lgA content obviously increase.It is the life-prolonging performance that old people lg increases.

4. be somebody's turn to do enhancing and the inhibitory action of the contained flavonoid composition in side to immunologic function, dual regulation: total flavones can improve the serum hemolysin antibody horizontal, increases the antibody-producting cell number, promotes to drench rate of rotation, the increase macrophage phagocytic function.But high concentration strong inhibition lymphocyte is to the breeder reaction of ConA, LPS, mixed lymphocyte reaction.Total allusion quotation ketone suppression ratio and drug level are proportional.Can prolong with the sharp allosome mouse heart transplanting survival phase simultaneously.

5. should side's polysaccharide, hyoscyami alkali class, glycyrrhizic acid, Herba Sophorae alopecuroidis alkali etc., biological alkali class can suppress the destruction of Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) to cardiovascular system hemopoietic system, marrow hemopoietic stem cells.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.

6. this side has the steroid hormone effect: and can stimulate the hypothalmus-pituitary-adrenal axis excitement, and the secretion that impels adrenal cortex to discharge Jiao element (CRH) increases, 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) antitoxic action.(4) Antishock function.(5) to metabolic effect.(6) to lymphocyte and blood cell effect.

7. this side has very strong immunosuppressive action and antiinflammatory action: analgesia, analgesic, calm, spasmolysis reach 93.45% to rheumatic arthritis 3-7 days pain relieving rates, the detumescence rate reaches 85.65% in 7 days, cure rate reaches 85.65%, obvious effective rate reaches 7.85%, effective percentage reaches 4.93%, total effective rate 98.43%, anti-chain " O " negative conversion rate 96%, the rheumatoid factor negative conversion rate reaches 76.6%.

8. 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, Herba Sophorae alopecuroidis alkali and glycyrrhizin, and it is the strongest that inhibitory action is induced to end effect in the 12nd hour at PHA.Herba Sophorae alopecuroidis alkali and glycyrrhizin are to CD ₄+ cell and CD ₈+ cell all has obvious inhibitory action, to CD ₄+ cyto-inhibition is the strongest.

9. we treat sick pharmacology such as rheumatic arthritis, rheumatoid arthritis, osteitis and sliding matter hypertrophy: 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 lgG antibody in the blocking-up rheumatoid arthritis patients body, and disease is eased.Also can make immunoreation trend hyperfunction in the body normal, clothes " the kidney warming rheumatism Drug Capsule " back patients serum lgG, lgM, lgA all reduce, and anti-chain " O " rheumatoid factor (RF) titre of turning out cloudy lowers or turns out cloudy, and the inhibition antibody nucleus formation of this Fang Youqiang is described.

Three, single pharmacological action:

(1) Herba Epimedii pharmacological action:

1. endocrine function is had and promote 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 Testosterone, is equivalent to the androgen effect.(2) Herba Epimedii is urged excessive effect, is because gonepoiesis is hyperfunction, after seminal fluid is full of, and 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 basal secretion of Ts and the stimulation secretion that human chorionic promotes glandular hormone, and can make the basal secretion of Ts and human chorionic promote the stimulation secretion of sex gland hormones, and or the secretion of Ts be increased by the CAMP approach by the CAMP approach.(4) Herba Epimedii is to hypothalamus-hypophysis---and the gonad axis function: Herba Epimedii can strengthen hypothalamic pituitary gonadal axis, adrenal cortex axle, the secretory function of secretion systems such as thymus axle.The Herba Epimedii extracting solution: the 1ml/100g body weight is given male rat, 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.

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 (lg) 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 lgG, lgA take medicine under normal value, lgG, lgA content obviously increase in the clothes Herba Epimedii bleeding from anus, and the increase of old people's immunoglobulin is the life-prolonging performance.

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 breeder reaction and the mice mixed lymphocyte reaction of ConA, LPS.Total flavones suppression ratio and drug level are proportional.Mouse stomach then can prolong the survival period of mice allogeneic heart transplantation.(2) total flavones is to the T lymhocyte transformation rate: the lower old people of the total active rosettes of rosettes (RtRFC) (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 (EPS) has antagonism to azidothymidine AZT inhibition mice hemopoietic and immunologic function: (1) gives mice azidothymidine AZT 80mg/kg, its peripheral blood leucocyte, marrow hemopoietic stem cells and grain monosystem CFU-GM quantity, the ability of spleen lymphocyte proliferation and generation interleukin II (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 ₃T ₄+ and Lyt ₂+ cell number reduces the mitogen irritant reaction is reduced; But this moment, thymocyte proliferation and generation IL-2 ability improved.The subcutaneous injection of 100mg/kg causes that mouse thymus discharges increase, enhancing body cellular immune function and organ immunologic function.(3) EPS has regulating action to human IL-2's generation: 2500ug and 5000ug/ml concentration cell survival rate are respectively 94% and 93%, are 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 (%mg/ml) effect of the Ea of increasing bow structure rate is arranged; High concentration reduces Ea bow structure rate on the contrary, proves that Herba Epimedii has dual regulation, and methanolic 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 cardiac muscle.The 10g/ml 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, suppresses 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 TA, MA and CA due to the high K+, the reaction of the contraction of CBA due to the 5-HT.(4) hypotensive effect: the Herba Epimedii decoct all has hypotensive effect for rabbit 2.5ml/kg, cat 2ml/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 the antagonism hydroxyurea is to the inhibitory action of ribonucleotide reductase, guarantee that nucleotide reducing becomes Deoxydization nucleotide TdR to mix DNA, finally promote DNA synthetic.Many in vitro testses 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%, injection has the growth of promotion effect to Embryo Gallus domesticus femur in vitro, medication group femur length, 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.Exempt from 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 the promotion purposes.

8. Herba Epimedii is to the maincenter effects on neural system: improve the mice hypoxia-bearing capability, the time-to-live often prolongs, and calmness and anticonvulsant action are arranged, and adjusting m receptor 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 normal 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, lgG 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 that reduces tissues such as LPO and the heart, liver forms, and the prompting total flavones improves the activity of SOD enzyme.Eliminate 02 free radical, protected cell to exempt from 02 infringement, delay organ and body aging effect.(3) Herba Epimedii can keep the normal adrenal cortex function of people and regulate immunologic function, postpones senescence 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, continuous 11 days, experiment in 1 hour after the last administration: administration 0.06g group swimming time 375.5 ± 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 is being exempted from blood Chinese medicine for dynamics research in the Herba Epimedii, is monitoring means with the Catalytic-Kinetic Analysis, utilizes the catalytic action of divalent manganesetion to Potassium metaperiodate .-rhodamine B reaction system.Use Phen to be activator, trace manganese has carried out fluoremetry in the blood to exempting from, curve MICROCOMPUTER PROCESSING as a result when having drawn medicine, and physiological disposition meets two Room open models, and obtains serial pharmacokinetic parameter.

11. toxicity, side effect: (1) Herba Epimedii extractum mouse peritoneal injection LD ₅₀Be 36g/kg.Extract the LD of the quiet notes of non-amino acid moiety (NO5-1-1) mice in the aqueous extract sheet ₅₀Be 56.8 ± 2.7g/kg.This product methanol extract liquid mouse gavaging 450g/kg.It is normal to observe activity as a result in 3 days continuously, no toxicity.(2) Herba Epimedii total flavones acute toxicity test: LD ₅₀2.99 ± 0.14g/kg is acute or subacute toxicity test: the extracting solution various dose is taken continuously, tissues such as the animal heart, liver,kidney,spleen is not had obviously change the harmless change of cell tissue outward appearance.

(2) Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) pharmacological action:

The research of Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) (belong to Aconitum carmichjaelii Debx. class medicine contain acetyl benzaconine) the kidney warming sun pharmacology: prove have analgesia, antiinflammatory, antiulcer, diarrhea, excited intestinal smooth muscle, anticoagulation, antithrombotic formation, shock, anti-hypoxia, resist myocardial ischemia, heart failure, anti-bradyarrhythmia effect, also have blood pressure regulation and the pharmacological action of glucocorticoid sample, this medicine also has the medical mechanism of antalgic, dispelling cold by warming the meridian dehumidifying, warm promoting blood circulation and recuperating depleted YANG and rescuing the patient from collapse.

1, antiinflammatory action: the 3-acetyl acetyl benzaconine of from the FUMAO Radix aconiti szechenyiani, getting, to dog, the swelling of mouse experiment inflammation, ooze out inflammation and granuloma induced by implantation of cotton pellets hypertrophy etc. obvious inhibitory action all arranged, and be dose-effect relationship, after being better than aspirin, adrenalectomize, effect still has the obvious anti-inflammatory and anti effect.Aconitum carmichjaelii Debx. time alkali because of lumbar injection acetic acid, causes that vascular permeability increases and the carrageenin foot swelling all has inhibitory action to mice.Nor-acetyl benzaconine has the oxygen-derived free radicals of removing, suppresses lipid peroxidation, oxidation resistance.The acetyl benzaconine class has the effect of glucocorticoid sample.

2, analgesic activity: Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) first, second, third, fourth element all have analgesic activity to mice.The total alkali analgesic activity of FUMAO Radix aconiti szechenyiani is stronger, be 43.7 times of morphine, but toxicity is about 300 times.3-acetyl acetyl benzaconine does not produce hopping response to the be improved threshold of pain effect of large and small Mus with nalorphine Cui addiction.Show that 3-acetyl acetyl benzaconine is a kind of not addiction analgesics.The Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) analgesic activity is relevant with concocting method, and licorice root products, oil product, urine goods analgesic effect are good, and Radix Glycyrrhizae also can be removed the infringement of Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) toxicity to people's various organ pipes.The local anesthesia effect: the total alkali of FUMAO Radix aconiti szechenyiani has stronger local anesthesia effect, act as the hydrochloric acid fourth long because of 14 times of for procaine hydrochloride 159 times.But toxicity is respectively the two 40 times and 180 times.Analgesic effect through the biological alkali 0.1mg/kg of High Temperature High Pressure separation and Extraction Aconitum carmichjaelii Debx. is also strong than morphine 6mg/kg effect.

3, to the cardiovascular system effect: Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) has approximate DE to the frog heart, and cardiac dysfunction due to it can be by atropic category medicine (this Radix Physochlainae is extracted hyoscyami alkali) antagonism.Herba Achilleae alkali first, second element is to exsomatizing and being the effect of acetyl benzaconine sample at the body frog heart.Radix aconiti szechenyiani immersion intravenous injection can cause anesthetized cat arrhythmia and blood pressure drops.Dosage strengthens this effect also to be strengthened.Hyoscyami alkali and glycyrrhizic acid can be removed the acetyl benzaconine class to cardiovascular system infringement and cardiac dysfunction among this side.

4, toxicity: the hydrochlorate of this product first, second, fourth element is given mouse subcutaneous injection: LD ₅₀Be respectively 21.96mg/kg, 2.99mg/kg, 70.09mg/kg.The LD of the total alkali intraperitoneal injection of mice of FUMAO Radix aconiti szechenyiani ₅₀Be 1.09mg/kg.With 4% Herba Achilleae tincture 5 or 15ml, irritate stomach to rabbit respectively, vomiting, unconsciousness etc. appear after preceding 15 minutes, and agitation, vomiting, large and small fecal incontinence both appearred in 10 minutes in the latter, and then extremity spasm, stupor etc. continue.Death in 30 minutes in 2 hours.Cuing open inspection sees in eyes retina and the brain extensively hemorrhage.Toxicity mainly reduces two aspects: the one, and the effect of parasympathetic nervous fever, the 2nd, directly poison cardiac muscle.

Advantages such as annotate: Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) is concocted new method can reduce toxicity: Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani) soaked into 48 hours, and 68Kpa, 120 ℃ steam 2 hours, acetyl benzaconine and resolve into aconine toxicity and fall and end 1/2000, and it is low to have toxicity, little to rhythm of the heart influence, and the respiration inhibition effect is weak.Acetyl group on 8 in the biological alkali of acetyl benzaconine class is replaced by some fatty acyl groups under water logging post-heating condition, generates the biological alkali class of the less fat of toxicity.

(3) Radix Physochlainae pharmacological action:

1, Radix Physochlainae mainly contains hyoscine and anisodamine atropic category medicine, and major part through enzyme hydrolysis, is discharged very fast in vivo distribution whole body at liver through kidney.

2, analgesia and Antishock function: hyoscine and anisodamine are suppressing cerebral cortex energy antagonism acetylcholine simultaneously, arteriole due to the catecholamine, vaso-active substances such as 5-hydroxy tryptamine, small venospasm, the about flesh of expansion is open before and after making blood capillary, the microcirculation improvement perfusion.Argument according to motherland's medical science " stagnation of QI and blood may bring about pain; general rule is not bitterly ", adopt the blood circulation promoting and blood stasis dispelling rule of treatment, use painful diseases such as hyoscyami class medicine treatment rheumatic and rheumatoid arthritis, this type of disease has the pathological process of vasospasm, blood supply insufficiency, microcirculation disturbance mostly, so can remove vasospasm with cholinolytic, microcirculation improvement and pain relieving.A series of dysbolismus take place in the circulation of improvement dimension, correction histanoxia, the shock state lower body are presented shock effects such as blood pressure rise, pulse pressure increase, hydrouria.

3, narcotic analgesic effect: give the indoor injection active ingredient of Medulla Leporis seu Oryctolagi hyoscine, animal righting reflex and audition disappear, and pain reaction is pure late, presents the light anaesthesia state.Clinical single depth of anesthesia that reaches with total alkali or hyoscine is equivalent to three phase one-levels of etherization, and increase dosage does not increase the degree of depth, instead sometimes causes side effect such as limb activity, muscular tone.Action principle is due to the anti-choline effect of central, because the choline of hyoscine cerebral cortex sensorimotor area can make endogenous acetylcholine (ACh) difficulty and receptors bind by cell muscarinic receptor (M-receptor), can not bring into play the function of mediator (for the mediator of excited maincenter), present maincenter and suppress.Cortex electrical activity test shows that hyoscine not only has anti-choline effect, also has adrenolytic, according to the electroencephalogram mutation analysis, thinks to block the reticular formation of brain stem ascending activating system and produces narcotic analgesic.

4, immunological enhancement: by the clinical observation of bronchial asthma and chronic bronchitis patient, most of patient's immunoglobulin A (lgA) lysozyme is had in various degree to be increased, and phagocyte increases in the sputum, and phagocytic function strengthens; The test of Intradermal allergy, positive degree alleviates or turns out cloudy.Eosinophil leucocyte descends in the blood.So Radix Physochlainae can be improved the body non-specific immunity and be regulated the emergency function of body, thereby enhancing body resistance against diseases.

5, toxic and side effects: the total alkali 75mg/kg of Radix Physochlainae gives the Canis familiaris L. intravenous injection, entered anesthesia in 3-4 minute, had a convulsion in 7 minutes, having annotated the back paroxysmal occurred in 1-10 minute and twitches strongly, even tonic convulsion, opisthotonus, each outbreak is special to continue 10-20 second, Canis familiaris L. still is in narcotism later on, occurs reviving after 1 hour.When giving 80mg/kg, poisoning symptom is to preceding similar, and is only more violent.Minimum lethal dose is greater than 75mg/kg, and less than 80mg/kg, than the big 37.5-40 of effective anesthesia amount 2mg/kg doubly.This product toxicity is little, to no material injuries such as the heart, liver, kidneys.That side effect has is flushing, xerostomia, slight platycoria, and it is fuzzy etc. to look nearly thing.Individual patients has dysuria (available neostigmine or galantamine are removed obstacle).Voluntary micturition in most 1-2 days.Utmost point individual patients has the mild skin anaphylaxis.Glaucoma, Acute Cerebral Hemorrhage are avoided usefulness.

(4) Herba Sophorae alopecuroidis pharmacological action:

1, Herba Sophorae alopecuroidis contains multiple biological alkali: the total alkali of Herba Sophorae alopecuroidis, matrine, oxidation matrine, sophoramine alkali, Chinese scholartree fruit alkali, Chinese scholartree are decided alkali, bitter bean alkali, cytisine, baptitoxine etc.

2, antiinflammatory action: the large and small Mus auricular concha exudative inflammation that the total alkali of Herba Sophorae alopecuroidis, matrine, oxidation matrine, Chinese scholartree fruit alkali bring out Oleum Tiglii, the toes swelling that diagonal angle fork bud glue brings out, and the chmice acute exudative inflammation that glacial acetic acid brings out all has remarkable inhibitory action, can reduce histamine and cause the penetrating increase of the thin blood vessel of the rabbit hair, increase the phagocytic function of mice inflammation emigrated cell.Its antiinflammatory degree is followed successively by matrine＞Chinese scholartree fruit alkali＞bitter bean alkali＞oxidation matrine, and its anti-inflammatory effect respectively has certain dose,optimum scope.After extracing the adrenal gland, its antiinflammatory action is still deposited.The total alkali of Herba Sophorae alopecuroidis brings out rat granuloma hypertrophy to cotton balls and does not make significant difference.

3, immunosuppressive action, immunologic enhancement: experiment shows that matrine, oxidation matrine, Chinese scholartree decide alkali, bitter bean alkali etc. intensive immunosuppressive action is arranged, the activation and the antibody that suppress the antibody forming cell synthesize; Suppress to rely on the anti-sheep red blood cell (SRBC) antibody formation of T cell; Suppress the mouse macrophage function; The tumor related immune serum lysozyme activity cell-mediated to T also has inhibitory action.Sophora alopecuroides alkali also has immunologic enhancement: decide alkali as Chinese scholartree and can promote lymphocyte transformation, macrophage and specific antibody generate.

4, analgesia, detumescence, sedation: (1) analgesia: total alkali, matrine, oxidation matrine, Chinese scholartree fruit alkali cause that because of chemistry or thermostimulation pain reaction all has obvious inhibitory action to mice.(2) detumescence: matrine, oxidation matrine, Chinese scholartree fruit alkali are to the experimental inhibitory action that swollen and ache.(3) calmness: total alkali, oxidation matrine, Chinese scholartree fruit alkali can significantly suppress the mice autonomic activities, can the antagonism sympamin or the excitation of caffeine, can also increase the death toll of fainting from fear due to the strychnine.

5, to cardiovascular effect: the total alkali of Herba Sophorae alopecuroidis has heart tonifying, arrhythmia, hypotensive activity.Can resist the arrhythmia that acetyl benzaconine, epinephrine, ouabain or ligation coronary artery bring out.It is good that matrine or oxidation matrine have been used to treat curative effect such as the early rich and paroxysmal tachycardia of arrhythmia, ventricular premature contraction, taking place frequently property.Can blood viscosity lowering and improve the hemorheology sexual abnormality.

6, cough-relieving, relieving asthma, spasmolysis: matrine, Chinese scholartree fruit alkali can shrink the isolated rat tracheal smooth muscle that antihistamine, acetylcholine and Barium monoxide etc. cause; Can excited midbrain B-adrenoceptor and function of relieving cough and calming asthma is arranged.Sophora alopecuroides alkali antihistaminic intensity is followed successively by bitter bean alkali＞Chinese scholartree and decides alkali＞total alkali＞cytisine＞matrine.The intensity of anti-5-HT is followed successively by total alkali＞bitter bean alkali＞cytisine＞Chinese scholartree and decides alkali.Vaso-active substances such as histamine and HT there is strong antagonism, the anaphylaxis exudative inflammation is had specially good effect, be used for the treatment of hypersensitive vasculitis.

7, matrine can reduce hyperlipidemia, fatty liver, the effect of removing free radical.

8, antibiotic, antivirus action: Herba Sophorae alopecuroidis alkali all has remarkable inhibitory action to streptococcus, staphylococcus, staphylococcus aureus, dysentery bacterium, Bacillus proteus, escherichia coli etc.To influenza virus, hepatitis virus HAV, HBV, NANBV all have very strong inhibitory action.

9, antitumor action: mouse ascites cancer, sarcoma 180 are all had higher therapeutic index.

10, diuresis: Herba Sophorae alopecuroidis alkali is given the oral or injection of rabbit, is produced diuresis.Before the urine amount increases, promptly have salinity to discharge to increase.

11, positive inotropic action: Herba Sophorae alopecuroidis alkali has strengthens the guinea pig papillary muscle contraction, to guinea-pig atrial, obvious positive inotropic action is arranged, may with activate Ca ₂ ⁺Passage is relevant.

12, physiological disposition: after having measured vein constant speed injection with the HPLC method, the concentration of Herba Sophorae alopecuroidis alkali in plasma in rabbit, to 10mg/kg, 15mg/kg, 20mg/kg, 30mg/kg, 60mg/kg, 5 dosage indexes carry out pharmacokinetic, and Herba Sophorae alopecuroidis alkali meets two Room open models at rabbit body giving drugs into nose for kinetics.12h discharges 9.39% from bile; Content in the Herba Sophorae alopecuroidis alkali tissue is followed successively by kidney, liver, brain, the heart and blood.48h urine, 24h excrement, 12 hours biliary original shape medicines are accumulated output, are respectively 53.7%, 0.36%, 0.27% of dose.

13, toxic and side effects: LD ₅₀(mg/kg) the mouse peritoneal injection 150; Rats by intraperitoneal injection 125.

(5) Radix Glycyrrhizae pharmacological action:

1. to the immunologic function systematic influence: (1) has anti-allergic effects: Radix Glycyrrhizae is extracted and contains body (LX) again and contain protein, nucleic acid, polysaccharide.Glycyrrhizic acid has strong anti-allergic effects, and the mouse allelgic shock is also had protective effect, and a variety of causes is caused that anaphylactic shock and dead suppression ratio are more than 95%.Glycyrrhizic acid 25-50mg/kg 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; 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 CP ₅₀And AP ₅₀All can suppress 50% haemolysis, can suppress complementary reaction, the related inflammation process is alleviated and is static.(4) influence of antagonist: 1. glycyrrhizic acid can make antibody significantly increase, and 30mg/kg can make antibody produce significantly enhancing.2. antagonist produces inhibitory action, Radix Glycyrrhizae and suppresses 1gE and contain that to become be 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 anaphylaxis of abnormality then is inhibitory action.(5) to the generation of interleukin II with induce the effect of r-interferon: glycyrrhizic acid 100mg/kg 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.200vg/ml increases ConA and induces 48 hours, cell concentration 1 * 10 ³/ ml is advisable, and it is main producing IFN-r.(6) prostaglandin (PGF2) 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 lung and kidney PGE ₂, PGF ₂Synthetic.Glycyrrhizic acid monoammonium awards mouse stomach 100mg/kg/ day (1/20LD ₅₀Amount) after 5 days, its spleen PGE ₂Significantly increase with the CAMP amount; The rat lymph-node cell is 8 * 10 ^-10Mo1/L and 8 * 7 ^-7Under the glycyrrhizic acid monoammonium concentration of mol/L, 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 all have the obvious anti-inflammatory and anti effect to animal rat formalin edema method, granuloma bag method, card circle's Seedling sensitization Corium Mus skin tuberculin inflammatory reaction.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 is by the metabolism that suppresses neutrophilic leukocyte, the formation that reduces active oxygen, 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 anaphylaxis and cause hyperemia, edema, ooze out, erythra, smooth muscle spasm and primary cellular defect, suppress the grafting device bank of tubes and scold 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 myocardial contraction, improve the dimension circulation, toxic shock, hemorrhagic shock, cardiogenic shock, anaphylactic shock are all had antagonism.(5) to metabolic effect: rising blood glucose and hepatic glycogen make the albuminolysis metabolism.(6) to lymphoid tissue and blood cell effect: heavy dose can make the thymic lymphoma knot, and spleen endolymph Telatrophy 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) enoxolone 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 Fm ₁₀₀Obvious analgesic activity is arranged, and the method for measuring the threshold of pain with the method for compressing mouse tail shows that more weak 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 subacid are at working concentration 8 * 10 ^-3Mg/ml and 4 * 10 ^-2During mg/ml, acetylcholinesterase is all produced obvious inhibitory action.Drug level during its 50% suppression ratio is respectively 25.6 ± 1.4ug/ml and 21.9 ± 1.1vg/ml.These two kinds of medicinal active ingredients all are competition to acetylcholinesterase---and non-competing type mixes and suppresses.

6. anti AIDS virus (HIV) effect, antibacterial action: (1) glycyrrhizin 0.5mg/ml forms inhibiting value 0.125mg/ml to proliferation inhibition rate 98%, 50% plaque of HIV, but can not suppress the reverse transcription of HIV, is to play 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 the proliferation function that suppresses tumor 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.It is the effect of testosterone that enoxolone 10vg/ml can suppress 17-B-hydroxysteroid dehydrogenase transformation androstanedione, causes gathering of 17-a-flavonol owing to above-mentioned enzyme is suppressed, and therefore, the enoxolone heavy dose has the mouse propagation of inhibition gland and produces 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. 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 30ug/ml, survey after 4 hours just to reach the peak, and medicine is 15ug/ml.Decay to 10ug/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 500ug/ml.(2) absorption of glycyrrhizic acid intravenously administrable: quiet notes 50,20mg/kg measures blood sample with the HPLC method, and the result shows that ammonium glycyrrhizinate descends 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 ± 0.46g/kg, lumbar injection LD ₅₀Be 6.8466g/kg, subcutaneous notes LD ₅₀Be 7.8192g/kg.Radix Glycyrrhizae extractum LD ₁₀₀Be 3.6mg/kg, the cause of the death is a respiratory 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 methanol extraction Fm ₁₀₀Mouse 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.Continuous 6 weeks of Radix Glycyrrhizae extractum 2g/kg every day gavage, and result and matched group comparison body weight have increase (but non-edema causes) slightly, do not have deadly in the experiment, check 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 makes mouse breathing suppress weight loss.

Specific embodiment

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

This kidney warming rheumatism medicine is capsule, and concrete prescription consists of icariine selenium, epimedium brevicornum polysaccharide, zinc glycyrrhetate, licoflavone, the total alkali manganese of Herba Sophorae alopecuroidis, hyoscyami alkali, aconine.Concrete proportioning is an icariine selenium 45.8%, epimedium brevicornum polysaccharide 7.6%, zinc glycyrrhetate 30.2%, licoflavone 7.6%, the total alkali manganese 7.6% of Herba Sophorae alopecuroidis, hyoscyami alkali 0.4%, aconine 0.8%.

The preparation technology of the kidney warming rheumatism medicine is specially:

(2) aconine extraction process:

(4) Herba Sophorae alopecuroidis alkali manganese extraction process:

(5) Radix Glycyrrhizae is extracted zinc glycyrrhetate:

3, glycyrrhiza residue and precipitate extract zinc glycyrrhetate, licoflavone: Radix Glycyrrhizae residue and precipitate add 1% zinc sulfate (ZnSO ₄) and 70% ethanol be lyase, hot dipping 8 hours, reflux 2 hours is filtered, continuous 2 times, merging filtrate reclaims ethanol, is condensed into cream, has both reclaimed zinc glycyrrhetate, licoflavone;

(6), preparation process: get the icariine selenium 50mg/kg/ day for preparing; Epimedium flavone 10mg/kg/ day; Epimedium brevicornum polysaccharide 10mg/kg/ day; Zinc glycyrrhetate 40mg/kg/ day; Licoflavone 10mg/kg/ day; The total alkali manganese of Herba Sophorae alopecuroidis 10mg/kg/ day; Hyoscyami alkali 0.41mg/kg/ day; Aconine 0.1mg/kg/ day, press the 50kg body weight per capita and calculate consumption, amount to 6525.5mg/50kg/ day, 14 capsules of packing, each capsule contains 466mg.

More than use icariine selenium, zinc glycyrrhetate in prescription, the technology, the selenium that wherein contains, zinc have following effects and purposes.

1, selenic effect and purposes:

(1) selenium can be kept the penetrating function of cardiac cell membrane, mitochondrial membrane, lysosome membrane and Golgi membrane, can stablize cardiac muscle, brain, kidney, pancreas cell system integrity, postpone the generation of irreversible damage, can at protein synthesis and promote to rise in the cytothesis process to pretend very much usefulness, selenium can quicken the reparation that cardiovascular and cerebrovascular vessel are filled in district's cell firmly, prolong anoxybiotic time-to-live of cardiac-cerebral ischemia and heart and brain automatic beats time, so, prevention and therapeutical effect are arranged to the cardio cerebrovascular affection that a variety of causes causes.

(2) lack selenium and can cause the heart, brain, vascular lesion, as: coronary heart disease, the heart, cerebrovascular arteriosclerosis, hypertension, deficiency myocardial blood supply, the heart power deficiency that contracts, myocardial infarction and cerebral infarction etc., selenium supplement can reverse and treat above-mentioned sick damage.

(3) lack selenium and can cause that osteoarthrosis produces pathological changes, as: Keshan disease, Kaschin-Beck disease, rheumatic and rheumatoid arthritis, osteoarticular injury etc. caused.

(4) lack selenium area cancer general mortality rate and increase, increase selenium and take in, can reduce the generation of cancer.

(5) selenium can also vision enhancing, immune stimulatory globulin and production of antibodies.Strengthen the ability of body resistance disease, make each organ of body avoid infringement.

(6) selenium is the cofactor of paddy Guang peptide peroxidase, has the effect of removing free radical and peroxide, makes body avoid the peroxide infringement.Prolong life, life lengthening.

(7) cardio cerebrovascular affection that diabetes are caused has prevention and therapeutical effect.Scarce selenium can make lipid catabolism unusual: bring out ketoboidies and produce---the diabetes ketosis, and ketoboidies ↑+---the bupropion metabolite product ↑---PH ↓---acidosis---diabetic ketoacidosis, selenium supplement can suppress diabetes ketosis and diabetes acidosis to albuminolysis.

(8) selenium consumption: Chinese's consumption 0.03-0.06mg/ day, international consumption 0.06mg/ day, toxic dose 6.35umol.

2, the effect of zinc and purposes:

(1) zinc participates in the body that 80 plurality of enzymes are synthetic, pancreas, gonad, activity pituitary all has zinc to participate in.

(2) zinc plays regulating action to human immunity.1. immunosuppressive action: suppress rheumatoid factor and produce, can suppress sick a large amount of lymphocyte and the plasmocyte infiltrating of synovial tissue of decreasing of rheumatoid arthritis, the lgG of degeneration and rheumatoid factor (RF) are formed immune complex in the synovial fluid.Because immune complex deposit on synovium of joint, swashs the complement system of having closed body, and promotes a large amount of neutrophilic granulocytes and macrophage, has engulfed and the bonded immune complex of complement, has just formed RA cell.2. suppressing the RA cell lysosome discharges a large amount of enzymes, quickens joint tissue is destroyed.3. suppress granulation tissue fibrosis or ossified in late period, stop articular surface to merge and form strong joint mutually.4. zinc supplement can make the atrophy gradually of muscle and skin, skeleton decalcification, osteoporosis be restored.5. can suppress rheumatoid arthrosis and granulation tissue hyperplasia, the immunoreation of strong inhibition rheumatoid factor is to bone, the heart, lung tissue, granulation tissue infringement and damage.

(3) zinc can be kept the normal development function of male's gland, and zinc deficiency can make oligospermia, and impotence generandi forms male sterility.Zinc supplement can reverse above-mentioned phenomenon.

(4) the human body barriers function can be safeguarded and strengthen to zinc, performance defence infection effect.

(5) zinc and cardiovascular and cerebrovascular vessel have certain relation, and zinc and cadmium be mutual antagonism in biosystem, and oral zinc can replace cadmium in the arterial wall, and expansion ischemic region blood vessel.

(6) zinc has the promotion growth promoter, improves the sense of taste etc., growth retardation during zinc deficiency, and nervous function depletion can have conjunctivitis, stomatitis, glossitis, inappetence, chronic diarrhea etc.

(7) zinc counts for much to upgrowth and development of children, and the zinc deficiency visible volume is thin and weak, mental retardation etc.

(8) feed ration: 10-15mg/ day, maximum 120mg/ day.

The indication of the kidney warming rheumatism medicine: be applicable to rheumatism numbness (rheumatic arthritis); In-particular king's numbness (rheumatoid arthritis); Rheumatism involving the bone (ankylosing spondylitis, hyperosteogeny, degenerative osteoarthropathy, hypertrophy bone change).

The untoward reaction of the kidney warming rheumatism medicine: a few peoples have gastrointestinal reaction (as: feel sick, go up general edema full etc.), formerly have the inclination, liver, gastropathy person have slight cardiac response and uncomfortable liver area.

The contraindication of the kidney warming rheumatism medicine: severe cardiac, liver, renal insufficiency person forbidding.The anemia of pregnant woman, to this product allergy sufferers, serious gastrointestinal disease person prohibit clothes, avoid with tea with obey, avoid with Cytotoxic drugs with clothes, seriously anemia (Hb＜80g/L) leukocyte is lower than 4 * 10 ⁹/ L, platelet is lower than normal person and prohibits clothes.

The usage and the consumption of the kidney warming rheumatism medicine: obey the 1-2 grain for the first time, day 1-2 time, if reactionless, can slowly add to 4, day 2-3 time, but but also took medicine 2-3 day one, interruption is taken.Neither have side effects and gastrointestinal reaction, curative effect is also definite, during meal or one after each meal, produce effects or take a turn for the better after, can slowly reduce to maintenance dose, day 3-6 grain, but still took medicine once determined curative effect in 2-3 days.

Claims

1. the kidney warming rheumatism medicine, its prescription consists of icariine selenium, epimedium brevicornum polysaccharide, zinc glycyrrhetate, licoflavone, the total alkali manganese of Herba Sophorae alopecuroidis, hyoscyami alkali, aconine;

Its content with everyone every kilogram every day consumption count: icariine selenium 60mg, epimedium brevicornum polysaccharide 10mg, zinc glycyrrhetate 40mg, licoflavone 10mg, the total alkali manganese of Herba Sophorae alopecuroidis 10mg, hyoscyami alkali 0.41mg, aconine 0.1mg;

The extracting method of each composition is:

(2) aconine extraction process:

(4) Herba Sophorae alopecuroidis alkali manganese extraction process:

(5) Radix Glycyrrhizae is extracted zinc glycyrrhetate:

(3), glycyrrhiza residue and precipitate extract zinc glycyrrhetate, licoflavone: Radix Glycyrrhizae residue and precipitate add 1% zinc sulfate (ZnSO ₄) and 70% ethanol be lyase, hot dipping 8 hours, reflux 2 hours is filtered, continuous 2 times, merging filtrate reclaims ethanol, is condensed into cream, has both reclaimed zinc glycyrrhetate, licoflavone.

2. the preparation technology of a kidney warming rheumatism medicine is specially:

(2) aconine extraction process:

(4) Herba Sophorae alopecuroidis alkali manganese extraction process:

(5) Radix Glycyrrhizae is extracted zinc glycyrrhetate:

(6), preparation process: get the icariine selenium 60mg/kg/ day for preparing; Epimedium brevicornum polysaccharide 10mg/kg/ day; Zinc glycyrrhetate 40mg/kg/ day; Licoflavone 10mg/kg/ day; The total alkali manganese of Herba Sophorae alopecuroidis 10mg/kg/ day; Hyoscyami alkali 0.41mg/kg/ day; Aconine 0.1mg/kg/ day, press the 50kg body weight per capita and calculate consumption, amount to 6525.5mg/50kg/ day, 14 capsules of packing, each capsule contains 466mg.