CN1300601A

CN1300601A - Recovery capsule for hepatitis and its preparing process

Info

Publication number: CN1300601A
Application number: CN 00119280
Authority: CN
Inventors: 辛耀禄
Original assignee: Individual
Current assignee: Individual
Priority date: 2000-06-30
Filing date: 2000-06-30
Publication date: 2001-06-27
Anticipated expiration: 2020-06-30
Also published as: CN1136869C

Abstract

A medicinal capsule for treating hepatitides including acute icterohepatitis, chronic viral hepatitides (chronic persisting hepatitis or chronic active hepatitis), acute severe hepatitis, etc. is prepared from schizandrin Se, alooerine Mn, archin Cr and liquorice Zn. Its advantages includes low cost and broad spectrum.

Description

Recovery capsule for hepatitis and preparation technology thereof

The present invention relates to the treating hepatitis medicine, especially a kind of hepatitis restoration curing capsule and preparation technology thereof.

Hepatitis is a kind of commonly encountered diseases, and general medicine extremely difficulty makes its radical cure.Though it is a lot of to treat the medicine of hepatitis at present, curative effect is not comprehensive, thorough, and price is excessively expensive, and the patient can not bear, and often therefore incurs loss through delay treatment of diseases.Also there is not a kind of treatment comprehensively, thoroughly at present, and the medicine of the low treatment hepatitis of price.

The purpose of this invention is to provide and a kind ofly can treat diseases such as acute icterohepatitisshock, chronic viral hepatitis (chronic persistent hepatitis, chronic active hepatitis), acute severe hepatitis, acute severe hepatitis (downright bad type, degeneration type), subacute severe hepatitis (subacute severe hepatitis), cholestatic hepatitis comprehensively, and cheap hepatitis restoration curing capsule and preparation technology thereof.

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

A kind of hepatitis restoration curing capsule is characterized in that prescription consists of schizandrin selenium Herba Sophorae alopecuroidis alkali manganese, emodin chromium, zinc glycyrrhizate.

The capsular preparation technology of this medicine " Ganyanfukangling " for curing hepatitis, concrete steps are:

(1) Fructus Schisandrae Chinensis extracts schizandrin selenium technology: get the Fructus Schisandrae Chinensis coarse powder, add 5 times of amounts of 1% sodium selenate, 95% ethanol warm macerating after 24 hours, and heating and refluxing extraction 3 times, each 1 hour, three times extracting solution merged, and filters decompression recycling ethanol, is condensed into cream, and dry back is standby;

(2) Herba Sophorae alopecuroidis alkali or root extract Herba Sophorae alopecuroidis alkali preparation of manganese:

The Herba Sophorae alopecuroidis root is a coarse powder, adds the extraordinarily hot reflux 1 hour of 1% manganese sulfate, 75% ethanol 5, and inclining medicinal liquid; The same method of medicinal residues adds 70% ethanol, 1% sulphuric acid heating and refluxing extraction 2 times again, and merge extractive liquid, left standstill 1-2 days, filters, and filtrate recycling ethanol to there not being the alcohol flavor, is condensed into cream, and dry back is standby;

(3) Radix Et Rhizoma Rhei extracts the emodin chromium process:

1. Radix Et Rhizoma Rhei decoction piece is with 0.2% chromic oxide gel Cr (OH) ₃, 5 times of amounts of 70% ethanol were soaked after 24 hours, 40 ℃ of reflux, extract, of low temperature, and each 10-15 minute, continuous dipping extracted 3 times with method, merges 3 times extracting solution, reclaimed ethanol, and concentrate under reduced pressure at low temperature becomes cream, the response rate 26%;

2. for the purity height, ointment adds 2 times of amounts of 70% ethanol again, smashes all, leaves standstill 12 hours precipitated impurities, extracts supernatant; Precipitation is with 45% washing with alcohol 2-3 time, and the solubility composition washes out in will precipitating, filtrate and washing liquid merging, and low temperature recovery ethanol, concentrating under reduced pressure is cooled to cream;

(4) Radix Glycyrrhizae is extracted zinc glycyrrhizate technology:

1. thick Radix Glycyrrhizae powder is measured 0.5% zinc carbonate ZnCO for 10 times with injection water ₃Seepage, continuous 3 times, effusion is concentrated into original volume 1/5 and filters, the acid of filtrate enriching stream transfers to PH3, filters and separates out precipitation, wash 3 times, drying below 60 ℃, both thick zinc glycyrrhetate (yield 10%);

2. pure product zinc glycyrrhizate extraction process: above gained crude product zinc glycyrrhizate 400g adds 4 times of amount ethanol, reflux 3 hours, and filtration, filtering residue add 2 times of amount alcohol heating reflux 2 times, merge all recovery liquid and add the 10g active carbon, reflux decolour cooling half an hour is filtered, and filtrate adds ZnCO ₃To PH greater than 7.5, till no solid is separated out.The filtrate precipitation, with the small amount of ethanol washing, drying at room temperature gets glycyrrhizic acid 250g;

3. glycyrrhiza residue extracts zinc glycyrrhizate: Radix Glycyrrhizae residue and precipitate add 1% zinc sulfate ZnSO ₄With 70% ethanol be lyase, hot dipping 8 hours, reflux 2 hours is filtered, continuous 2 times, merging filtrate reclaims ethanol, is condensed into cream;

(5) select the best safety consumption for use

Schizandrin selenium 3mg/kg/ day;

Herba Sophorae alopecuroidis alkali manganese 10mg/kg/ day;

Emodin chromium 40mg/kg/ day;

Zinc glycyrrhizate 5mg/kg/ day;

Amount to daily 2900mg/50kg/ day;

Be divided into and adorn 6 large size capsules, each contains 0.483g.

Characteristics of the present invention, pharmacology and effect are as follows:

One, the capsular side's medicine of medicine " Ganyanfukangling " for curing hepatitis characteristics:

1. we have the novelty reasonable recipe: be made up of Fructus Schisandrae Chinensis, Herba Sophorae alopecuroidis, Radix Et Rhizoma Rhei, Radix Glycyrrhizae.Have efficient, quick-acting, low toxicity, the minimum characteristics of side effect.We have dispelling toxicity, detoxicating, clearing away heat-damp and promoting diuresis, blood circulation promoting and blood stasis dispelling, circulation of qi promoting dispersing the stagnated live-QI to relieve the stagnation of QI, strong antivirus action.To what start an inflammation of the liver: hepatitis A virus (HAV), hepatitis B virus (HBV), non A non B hepatitis virus (NANBV) have very strong inhibition and killing action.Very strong immunostimulant and antiinflammatory action.Reduce great three positive, small three positive fast; Promote ribonucleic acid (DNA) and protein synthesis, DNA mitochondrial DNA is recovered and increase, enzyme activity strengthens, hepatocyte recovers and regeneration, the effect of performance alt-reducing and liver-protecting.We have expelling of toxin, normalizing gallbladder, remove stasis of blood gallbladder and obstructive jaundice, prevent and treat various hepatitis, fatty liver, hepatic fibrosis, liver cirrhosis, hepatic necrosis, hepatocarcinoma.And can prevent and treat the various complication of hepatitis, get well life lengthening fast.

(1) quick-acting: taking medicine 1-3 days is visible positive effect.

(2) efficient: after 97.73% people takes medicine very good effect is arranged, the scorching patient's 264 example healings for the treatment of the liver 199 examples account for 75.38% altogether; Produce effects 44 examples account for 16.67%; Effective 15 examples account for 5.68%; Invalid 6 examples account for 2.27%; Total effective rate 97.73%.

(3) nontoxic: taking medicine according to 264 examples did not occur toxic reaction in 1-3 month.

2. our extraction process advanced person: use trace element, acid, alkali, temperature control, novel process for purifying, the extraction ratio height, curative effect is compared with similar medicine and is improved more than 150%.For example

(1) sodium selenate extracts schizandrin selenium, can make schizandrin selenium hepatocyte injury due to the hepatitis virus be repaired as early as possible and regenerate, and alt-reducing and liver-protecting also has the control liver cirrhosis.

(2) extract emodin chromium, chrysophanic acid chromium with chromic oxide gel, existing strong inhibition and kill the hepatitis virus effect has the serum bilirubin of reduction, blood fat reducing, fatty liver and atherosclerosis effect again.Strong toxin expelling, function of gallbladder promoting, hepatoprotective effect; Remove bile capillary toxin, slough and foreign body in the liver; Eliminate stasis of blood gallbladder and obstructive jaundice.Chromium is the Fructus Vitis viniferae tolerance factor, prevent and treat hepatitis after diabetes take place, emodin chromium also has anti-cancer, tumor effect.

(3) extract Herba Sophorae alopecuroidis alkali manganese with manganese sulfate: the existing very strong hepatitis virus resisting effect of Herba Sophorae alopecuroidis alkali manganese has the anti inflammatory detoxication effect again.Reduce capillary permeability, eliminate the sick element of hepatitis hepatocyte is soaked evil, control hepatic fibrosis, Herba Sophorae alopecuroidis alkali manganese can make the neural blood vessel wall loose, reach the blood vessel dilating effect, promote liver, the heart, and the blood supply of kidney, control dimension vascular lesion, important organ and neural the damage, and very strong immunological enhancement is arranged.Herba Sophorae alopecuroidis alkali manganese is the important composition composition of enzyme, and energy kinase activity plays an important role to endocrine regulation and adjusting immunologic function.Promote insulin secretion blood sugar regulation, the liver protecting and ALT lowering, remove free radical slow down aging, longevity.

(4) extract zinc glycyrrhetate with zinc carbonate, existing detoxifcation hepatoprotective effect again can raise immunity.It is synthetic that zinc glycyrrhizate can participate in interior 80 plurality of enzymes of body, and performance defence infection effect can be expanded the ischemic region blood vessel, also have antiinflammatory action.

3. we have very strong antibiotic, antivirus action: to hepatitis A virus (HAV), hepatitis B virus (HBV), the non A non B hepatitis virus (NANBV) that starts an inflammation of the liver, have and suppress and killing action, to various bacteria, fungus, viral concurrent infection all have inhibition and killing action.

4. we have very strong alt-reducing and liver-protecting effect: promote hepatocyte nucleic acid, protein synthesis, DNA mitochondrial DNA is recovered and is increased, and enzyme activity increases, and hepatocyte recovers and regeneration, the effect of performance alt-reducing and liver-protecting.

5. immune system is had and emphasize very much the joint effect: cellular immunization, humoral immunization inhibitory action and potentiation are arranged; Can induce r-interferon (IFN-r), interleukin II (IL-2), interleukin 3 (IL-3), a tumor necrosis factor (TNF-a), B-transforming factor (TGF-B1), HIV-1 inhibitive factor, natural killer cell (NK cell).These immunologic active materials to regulate immunity, suppress liver inflammatory reaction, prevent and treat hepatic necrosis, hepatic fibrosis, liver cirrhosis, liver tumor, inhibition HAV, HBV, NANBV remarkable effect arranged.

6. our medicine has very strong dispelling toxicity, detoxicating effect, anti-allergic effects, antiinflammatory action, reduces capillary permeability, can remove hepatitis virus to hepatocellular infringement, and hepatocyte in damaged condition is promoted nucleic acid, protein synthesis, and hepatocyte is repaired as early as possible.

7. our strong inhibition, treatment hepatitis complication, large and small, the artery and vein of expansion nutrition hepatic tissue, blood fat reducing, treatment of vascular is atherosis, control fatty liver, liver cirrhosis, hepatitis complication with diabetes, hyperbilirubinemia, cholangitis, cholecystitis, aplastic anemia, hepatic encephalopathy, neuropathy is prevented and treated conscience kidney brain complication and is taken place and development.

8. to jaundice, cholestatic hepatitis: this medicine has expelling of toxin, normalizing gallbladder, function for protecting liver and reducing enzyme activity.The powerful interior bile capillary of liver of expanding, interior, the bile capillary endotoxin of removing liver, slough and foreign body are eliminated stasis of blood gallbladder phenomenon, help jaundice, cholestatic hepatitis recovery.

Two, the pharmacological action of recovery capsule for hepatitis:

The Fructus Schisandrae Chinensis pharmacological action

1. hepatoprotective effect: schisandrin B can alleviate or suppress the hepatic injury due to carbon tetrachloride or the thioacetamide, and high glutamate pyruvate transaminase is reduced, and the second element significantly increases the content of moisture, protein, ribonucleic acid and total fat in the every gram hepatic tissue of normal mouse.The content of DNA (deoxyribonucleic acid) reduces slightly in every gram hepatic tissue, and the content no change of full liver DNA (deoxyribonucleic acid).The second element has obvious promotion hypertrophy, promotes protein synthesis and the synthetic effect of nucleic acid the liver of part excision.The second element has inducing action to the hepatomicrosome drug metabolizing enzyme, and P-450 concentration, NADPH (codehydrogenase)-cytochrome reductase, aminophenazone demethylase, microsomal protein are all significantly increased; The detoxification ability of body can be improved, the animal dead that digitophyllin and indometacin are poisoned and caused can be reduced some poisonous substance (carbon tetrachloride etc.) and chemical carcinogens (as benzopyrene).

Schisandrin B has inhibitory action to the foundation of microsomal Lipid Peroxidation that the hepatotoxic agent carbon tetrachloride causes, the generation of hepatocyte malonaldehyde and the release of LDH and GPT enzyme are all reduced, and the hepatocyte survival rate improves, and the cell membrane form is kept perfectly.

2. to metabolism and Immune Effects: schisandrin B can obviously promote exogenous glucose to generate liver glycogen.Schisandrin B is in inducing mouse and the increase of rat liver microsomes cytochrome P-450, also cause that liver glutathione-S-transferase (GSH-S-T) obviously increases, can urge the effect that the castration mouse uterus weight increases by the antagonism estradiol, reduce the effect that the short castration mouse uterus weight of mice serum estradiol increases, reduce the concentration of mice serum estradiol.Radioimmunity and high-efficient liquid phase technique confirm that schisandrin B can promote the speed of Mouse Liver microsome metabolism [3H] estradiol.

Schisandrin B has cytotoxicity to leukemia and KB cell.Mouse ascites hepatocarcinoma and S180-V cancerous cell [3H] TdR to In vitro culture mix the DNA effect, and the suppression ratio of 99 g/ml is respectively 85% and 76%.Human embryonic cells or fibrocellular suppression ratio are had only 50%.To [32P] sodium hydrogen phosphate participate in nucleoprotein 12,14,36 and 48h cultivate the back suppression ratio and be respectively 12%, 30%, 37% and 33%.Be respectively 56%, 58%, 50% and 66% to mixing ATP radioactive intensity suppression ratio.

3. to central nervous system's effect: schisandrin B can obviously prolong the length of one's sleep of mice to pentobarbital sodium or ring second barbital sodium, to the two-phase influence of shortening is arranged after prolonging length of one's sleep of mice.To the prolongation of the length of one's sleep is because the hepatocyte microsome enzyme is suppressed, and make later on shorten the length of one's sleep for this reason fermentoid induced and make barbital sodium accelerate the failure so.

4. toxic action: schisandrin B toxicity is lower, and 2g/kg irritates stomach once, none death of 10 Mus.200mg/kg irritates stomach once every day, and continuous 30d there is no obvious influence to the tissue morphology of mice growth, hemoglobin and main organs.10mg/kg irritates stomach once a day to Canis familiaris L., continuous 4 weeks, its content, body weight, hemogram, liver function, kidney merit and hepatic tissue biopsy all with the preceding no significant difference of administration.

The Herba Sophorae alopecuroidis pharmacological action

1. antiinflammatory action: the intramuscular injection of oxidation Herba Sophorae alopecuroidis alkali is similar to hydrocortisone, can obviously resist the exudative inflammation that Oleum Tiglii, carrageenin (rat) and glacial acetic acid (mice) bring out.Invalid to rat by the chronic inflammatory disease that cotton balls brings out, and hydrocortisone has obvious curative effects.Its anti-acute inflammation and hypophysis-adrenal system are irrelevant.In vitro experimental results show that it is direct reaction.

2. resisting pathogenic microbes effect

(1) antibacterial action: studies show that Herba Sophorae alopecuroidis alkali has anti-lamb dysentery Type B clostridieum welchii and the effect of anti-sheep escherichia coli, each experimental group and the equal highly significant of matched group difference in vivo.Action intensity and chloromycetin contrast in the body of Herba Sophorae alopecuroidis alkali, and difference is not remarkable.Experiment in vitro proves that 1% Herba Sophorae alopecuroidis alkali all has the obvious suppression effect to dysentery bacterium, Bacillus proteus, group B streptococcus and staphylococcus aureus.0.3% Herba Sophorae alopecuroidis aqueous slkali has inhibitory action to B-mode coccus, when its concentration increases to 1%, dysentery bacterium, modification bacillus, escherichia coli, staphylococcus aureus is also had good inhibitory effect.

Herba Sophorae alopecuroidis alkali has anti-Pullorum Disease Salmonella effect in vivo.Action intensity in the body of Herba Sophorae alopecuroidis alkali, through contrasting with chloromycetin, difference is remarkable (P＞0.05) not.

According to another report, all there is antibacterial action Herba Sophorae alopecuroidis alkali inside and outside, and action intensity is suitable with chloromycetin in the body.

Have the scholar to make Chinese medicine such as Herba Sophorae alopecuroidis alkali 100 routine suppurative otitis media patient's puss are carried out cell culture and bacteriostatic experiment research, secondly experiment is bacillus pyocyaneus, viridans streptococci, aerobacteria, escherichia coli and Bacillus proteus based on staphylococcus.The Chinese medicine drug sensitive test finds that Rhizoma Coptidis, Radix Scutellariae, Herba Senecionis Scandentis, Herba Sophorae alopecuroidis are to Fructus Vitis viniferae ball sensitivity, Fructus Mume is all responsive to staphylococcus and green pus bacterium, by the detumescence test of medicine to the mouse ear inflammatory model, the result is the most obvious for the detumescence of Herba Sophorae alopecuroidis alkali, secondly be Ilex purpurea Hassk.[I.chinensis Sims, Radix Scutellariae, Herba Houttuyniae, this shows that Herba Sophorae alopecuroidis alkali has antibacterial and anti-inflammation functions preferably.

16 kinds of Chinese medicines such as Herba Sophorae alopecuroidis alkali have one antibacterial action to gardnerella vaginalis.Select 16 kinds of infection Chinese herbal medicine for use, be prepared into the medicinal liquid that contains crude drug 1g/ml, 10 strain gardnerella vaginalis (GV) are carried out extracorporeal bacteria inhibitor test with cup-plate method.The result shows that gardnerella vaginalis (GV) is extremely sensitive to Radix Scutellariae; To Herba Sophorae alopecuroidis alkali etc. is medium sensitivity.Experiment for the further investigation and clinical practice Chinese herbal treatment bacterial vaginosis enlightenment is provided, also point out Herba Sophorae alopecuroidis alkali that the antibacterial action of wider range is arranged.

(2) antivirus action: the scholar is arranged to 21 kinds of anti-DHB initial research of Chinese medicine, the DHBV DNA in 263 parts of 2-3 of Chongqing region monthly age sheldrake serum that adopted detected by dot blot hybridization, through the negative duckling of the serum DHBV of abdominal cavity infection 1-2 age in days DNA, and 21 kinds of Chinese medicine anti-hepatitis virus primary dcreening operations have been carried out with the positive-virus serum that filters out with this model.The result shows: 1. Chongqing region 2-3 monthly age sheldrake DHBV natural infection rate is 25.48%.2. be 82.90% after 1 week through the serum DHBV DNA of the 1-2 of abdominal cavity infection age in days duckling positive rate.And sustainable at least 2 months.3. anti-hepatitis virus Chinese medicine primary dcreening operation is found to treat with Guangxi Cacumen Securinegae Suffruticosae, Herba Sophorae alopecuroidis alkali and can be made the decline of DHBV DNA titre 2 weeks, and remaining thinks effective anti-hepatitis virus Chinese medicine through experiment in vitro, and zoopery does not obtain confirmation.Experimental result prompting Herba Sophorae alopecuroidis alkali has certain antivirus action.

3. to central nervous system's effect: Herba Sophorae alopecuroidis alkali is injected in rabbit, finds nervus centralis paralysis phenomenon, and spasm takes place simultaneously, whole then respiratory arrest and extremely.Be injected in Rana nigromaculata, just be excited, the then paralysis that continues is breathed and is become slowly and irregularly, and spasm takes place at last, so that respiratory arrest and dead; The outbreak of its spasm is arise from spinal reflex hyperfunction.

Herba Sophorae alopecuroidis alkali can obviously suppress the autonomic activities of mice, the central excitation effect of antagonism amfetamine and caffeine, the central inhibitory action of enhancing pentobarbital sodium and chloral hydrate.Writhing method and thermostimulation method are surveyed the pain test and are shown that Herba Sophorae alopecuroidis alkali has analgesic activity, behind the Herba Sophorae alopecuroidis alkali of icv trace, still can significantly improve the pain threshold of mice.Its analgesia position may be at maincenter.Herba Sophorae alopecuroidis alkali reduces the effect of rat normal body temperature in addition.

Herba Sophorae alopecuroidis alkali can raise the dopamine metabolite dihydroxy acetic acid (DOPAC) of rat striatum and forebrain marginal zone and the content of 4-hydroxy-3-methoxy-.alpha.-toluic acid. (HVA).

4. antitumor action: Herba Sophorae alopecuroidis alkali 2.5mg/kg is external and interior animal experiment is all effective to the mice ehrlich carcinoma, and is also effective to murine sarcoma 180.Therapeutic index is higher, and about 1/30 and 1/60.

Herba Sophorae alopecuroidis alkali stimulates the Turnover of Mouse Peritoneal Macrophages that produces to suppress the effect of P615 tumor cell proliferation external can the reduction by the thiacetic acid. preparation of sodium.

5. antiarrhythmic effect: rat iv Herba Sophorae alopecuroidis alkali can significantly resist the arrhythmia due to aconitine, barium chloride and the ligation arteria coronaria.18.75mg/kg heart rate is obviously slowed down, and P-R and Q-T1 interval, obviously prolong.The 200 μ mol/L spontaneous frequency of isolated rat right atrium that significantly slows down, the heart rate that antagonism Herba Sophorae alopecuroidis alkali SO brings out is accelerated, and amount one is imitated the non-equality of curve and is moved to right, and obviously antagonism isolated rat left ventricle is accelerated by the heart rate that NE brings out.The effect that Herba Sophorae alopecuroidis alkali has negativity frequency, negativity self-disciplining and prolongs effective refractory period heart.Therefore can produce antiarrhythmic effect.This is with clinical used anti-arrhythmic is obviously different at present.May be useful to the congestive heart failure patient.

6. diuresis: Herba Sophorae alopecuroidis alkali gives rabbit oral or injection, produces diuresis.Increasing of salinity discharge before increasing, the urine amount promptly arranged.

7. positive inotropic action: Herba Sophorae alopecuroidis alkali has the contraction of the guinea pig papillary muscle of reinforcement, and guinea-pig atrial is also had obvious positive inotropic action, may be relevant with activation Ca2+ passage.

8. physiological disposition: measured the concentration of vein constant speed injection back Herba Sophorae alopecuroidis alkali in plasma in rabbit with the HPLC method, to 10mg/kg, 15mg/kg, 20mg/kg, 30mg/kg, 60mg/kg, 5 dosage groups are carried out the pharmacokinetic result and shown: Herba Sophorae alopecuroidis alkali meets two Room open models at rabbit body giving drugs into nose for kinetics.T1/2 β, Ve, CLS are similar substantially during 10-30mg/kg, and the proportional increase of AUS and dosage is linear and eliminates.During 60mg/kg, t1/2 significant prolongation, AUC hypergeometric example increases, and is non-linear elimination.Rabbit experiment shows, iv Herba Sophorae alopecuroidis alkali, blood drug level one time graph are two exponential types, meet open two-compartment model, and T1/2 is 1.37min, and T1/2 β is 76.58min, and Cl is that 23.59ml/ (minkg) vd is 2.61L/kg.12h urinates biliary original shape medicine accumulation output and is respectively 9.39%, 0.37% of dosage.Rat experiment shows that the content in the ig Herba Sophorae alopecuroidis alkali tissue is followed successively by kidney, liver, brain, the heart and blood.The biliary original shape medicine accumulation of 48h urine, 24h excrement and 12h output, be respectively 53.7%, 0.36% and 0.27% of dosage.

9. toxic action: LD50 (mg/kg): mouse peritoneal injection 150, rats by intraperitoneal injection 125.

The Radix Et Rhizoma Rhei pharmacological action

1. to the influence of liver: Radix Et Rhizoma Rhei has significant protective effect to experimental hepatic injury.Cause mouse liver injury with CC14, SGPT is up to 616.0u/100ml, the normal control group only is 289, after rhubarb treatment, SGPT reduces to 325.3u/100ml, hepatic necrosis degree, degeneration are all light than simple CC14 group, further cause rat liver fibrosis with D-two methyllanthionines, observe the therapeutical effect of Radix Et Rhizoma Rhei with histochemistry and Ultrastructural variation, find that Radix Et Rhizoma Rhei can reverse significantly that the fat that occurs in the hepatic tissue that CC14 causes drips and fibrosis, microsome swelling, ridge obviously descend, rough endoplasmic reticulum destroys, ribosome significantly comes off etc.Also can recover weakening of MAO that CC14 causes and succinum alcoholdehydrogenase.Show that the hepatic injury that Radix Et Rhizoma Rhei causes CC14 truly has prevention and therapeutical effect.Experiment in vitro proves that the Radix Et Rhizoma Rhei decoct has the obvious suppression effect to hbs antigen (HBsAg).

2. choleretic effect: Radix Et Rhizoma Rhei can promote the bile secretion of Canis familiaris L., and the content of bilirubin and bile acid is increased.Rat experiment proves that big yellow fluid, alcohol extract, Radix Et Rhizoma Rhei decoct all make bile flow obviously increase, and its peak is in administration 30 minutes.Observe to find to take with B ultrasonic give birth to, behind the Radix et Rhizoma Rhei (processed) in 0.5 and 1 hour gallbladder obviously greater than before the clothes Radix Et Rhizoma Rhei, also can promote the biliary secretion of experimental acute suppurative cholecystitis, the prompting Radix Et Rhizoma Rhei is significantly increased the composition of bile secretion, also have it to suppress composition, this preparation research and clinical practice for Radix Et Rhizoma Rhei provides certain clue.

3. promote the pancreatic secretion effect: experimental results show that acute edema type or downright bad pancreatitic generation of type of acute hemorrhage and development that Radix Et Rhizoma Rhei can prevent that trypsin or ethanol from bringing out.Tissue hyper-microstructure confirms that it also has the obvious treatment effect to the pancreas in rat inflammation that D-two methyllanthionines cause.In 30 minutes, pancreatic juice all obviously increases after administration for Radix Et Rhizoma Rhei decoct and preparation, and dosage strengthens, and effect is strengthened, and it is more of a specified duration to hold time.The Radix Et Rhizoma Rhei decoct in vitro reaches under the analog approximation gastrointestinal tract environment, and the activity of trypsin, pancreatic lipase and pancreatic amylase is had the obvious suppression effect, and to the not influence of pepsic activity.In a word, Radix Et Rhizoma Rhei and extract thereof have the effect of significant promotion pancreatic secretion, may be relevant with the lax Ao Dishi sphincter tone of Radix Et Rhizoma Rhei, and Radix Et Rhizoma Rhei may be the pancreatitic basis of rhubarb treatment to the influence of three kinds of digestive enzyme of pancreatic secretion.

4. to the influence of pathogenic microorganism

(1) antibacterial action: experimental results show that Radix Et Rhizoma Rhei all has in various degree inhibitory action to staphylococcus, Hemolytic streptococcus, diphtheria corynebacterium, bacillus subtilis, Mycobacterium phlei, brucella, bacillus pestis, typhoid fever, Salmonella paratyphi, dysentery bacterium, deep shape bacillus, bacillus smegmatis, gonorrhea diplococcus etc., the most responsive with staphylococcus, gonorrhea diplococcus especially.3-carboxyl rhein, hydroxyl aloe-emodin, hydroxyemodin three antibacterial action are the strongest.

Chrysophanic acid, emodin, aloe-emodin are 1.5-25mcg/ml to the inhibition concentration of staphylococcus, streptococcus, diphtheria corynebacterium, bacillus subtilis, anthrax bacillus, Bacillus typhi etc.Emodin, aloe-emodin are respectively 15mg/l, 480mg/l, 120mg/l and 7.5mg/1,600mg/1,60mg/1 to staphylococcus aureus 209P, escherichia coli, shigella flexneri at external minimum inhibitory concentration.To clinical isolating 119 strain staphylococcus aureus minimum inhibitory concentrations, emodin is 20-160mg/1, and aloe-emodin is 10-80mg/l.After the inducible resistance test, aloe-emodin produces drug resistance, and emodin does not produce drug resistance.Radix Et Rhizoma Rhei antibacterial action mechanism mainly is to bacterial cell nucleic acid and protein synthesis and glycometabolic inhibitory action.

(2) antifungic action: the extractum of Radix Et Rhizoma Rhei decoct and water, alcohol, ether has inhibitory action to some common pathogenic funguses in vitro, and responsive strain has oidium schoenleinii and Mongolian mutation thereof, Trichophyton concentricunm, trichophyton, star nocardia, sufficient sole of the foot trichophyton, acrothesium floccosum, trichophyton gypseum, trichophyton interdigitale, sporotrichum schenckii etc.

(3) antivirus action: the susceptible poison of Radix Et Rhizoma Rhei decoct convection current has stronger inhibitory action, and hepatitis virus is also had stronger inhibitory action.

(4) parasiticide effect: the Radix Et Rhizoma Rhei leachate can kill histolytica distortion protozoon respectively in the concentration of 1: 5000 and 1: 1000, can kill Trichomonas hominis at 1: 5000, and a little less than the inhibition to intestinal infusorian and Wan Shi lip whipworm.Emodin has 40% suppression ratio to the mouse infection schistosomicide.The concentration of wild Radix Et Rhizoma Rhei 1% can make cercaria dead in 90 minutes.5% Radix Et Rhizoma Rhei leachate can make culex pipiens pallens larvae dead 50% in 48 hours.

(5) discharge function: Radix Et Rhizoma Rhei has discharge function.Promptly as cathartic, be used for the treatment of constipation due to dry stool, constipation with heat retention since ancient times, generally after medication, can discharge loose stool in 6-19 hour.The Senna fruit glycoside is the effective ingredient of Radix Et Rhizoma Rhei diarrhea inducing, and visible Radix Et Rhizoma Rhei has excited and suppresses the gastrointestinal dual function, and the material base of this effect is exactly Senna fruit glycoside and tannin class.

(6) to the influence of gastric and duodenal ulcers: Radix Et Rhizoma Rhei can be treated and be prevented the hemorrhage of stress gastric ulcer, shows as extent of hemorrhage and obviously alleviates, and hemorrhagic focus, hemorrhagic focus area obviously reduce, and its effect is similar to cimetidine.

(7) to the influence of intestinal tube electrical activity and contraction movement: electric Physiological Experiment proves, Radix Et Rhizoma Rhei has tangible excitation to the electrical activity of whole colon, characteristics are the gregariousness discharge, peak electricity frequency obviously speeds, amplitude obviously increases, this explanation Radix Et Rhizoma Rhei hinders the colonic moisture absorption by excited intestinal electrical activity, accelerate the discharge of colonic contents and bring into play its discharge function, low dose suppresses the colon electrical activity, heavy dose makes the excitement of intestinal electrical activity, sometimes excited earlier back then occurs and suppress phenomenon, bring into play its discharge function by acting on m receptor in the intestinal tube.

(8) to the influence of heart: the emodin low dose is strengthened the isolated heart contractility, and heavy dose then suppresses.Radix Et Rhizoma Rhei can make the MAP amplitude of heart increase, and climbing speed speeds, and myocardial contraction obviously strengthens, and proves that Radix Et Rhizoma Rhei has significantly cardiotonic.Increase that K+ concentration can weaken the toxic action of heavy dose of Radix Et Rhizoma Rhei to heart in the extracellular fluid, the cardiotonic of prompting Radix Et Rhizoma Rhei may with the Na+ that suppresses on the cell membrane, the K+-ATP enzyme is relevant.Rhubarb polyoses can make the normal rat blood pressure drops, and decreased heart rate makes normal and depleted Bufo siccus cardiac contractile force and the cardiac output of exsomatizing increases, the prompting cardiotonic may be by suppress Myocardial Na+, the K+-ATP enzyme is realized.

(9) to the influence of blood vessel: Radix Et Rhizoma Rhei preserved material, tincture and emodin all have the effect that brings high blood pressure down.The Radix Et Rhizoma Rhei tincture can make rabbit ear vasodilation.

(10) stop blooding and the effect of invigorating blood circulation: the hemostasis effective ingredient α-catechin of Radix Et Rhizoma Rhei and gallic acid can reduce the activity of Antithrombin II (AT II), the content of rising α 2-MG (alpha2 Macroglobulin), the vigor that suppresses fibrinolysin and plasminogen activin competitively, the fibrinolytic vigor is descended, and the adhesiveness of platelet increasing and ability of aggregation, thereby quicken hemostasis.

(11) blood fat reducing and antiobesity action: rhubarb polyoses can make egg yolk and the inductive hyperlipidemia mice serum of high lipid food and total cholesterol of liver (TC), triglyceride (TG) obviously reduce, may be relevant with anorexia and cathartic.There is the effect of tangible reduction serum total cholesterol at the alcohol extraction position of Radix Et Rhizoma Rhei.The effect of ligroin extraction cholesterol reducing is not remarkable.Clinical observation has tangible antiobesity action to living, Radix Et Rhizoma Rhei, and its blood fat reducing and fat-reducing composition may be anthraquinone class, catechin compounds, and polysaccharide also has these effects.

(12) chrysophanic acid of antitumor action: 5mg/kg and emodin are respectively the suppression ratio of murine melanoma] 76% and 73%.Emodin has significant competitive inhibition to tyrosinase, and this inhibitory action may be one of mechanism of action of Radix Et Rhizoma Rhei melanoma.

(13) to Immune Effects: emodin and aloe-emodin lumbar injection 70mg/kg7d have in various degree inhibitory action to normal mouse immune system, as alleviate the weight of immune organ, reduce production of antibodies, suppress carbon clearance function and peritoneal macrophage phagocytic function, reduce leukocyte count, delayed hypersensitivity due to the inhibition 2,4-dinitrochlorobenzene (DNCB).

(14) to the influence of kidney: Radix Et Rhizoma Rhei has the effect of non-protein nitrogen in the tangible reduction blood, this effect may be owing to reduced the absorption of intestinal to amino nitrogen (raw material of urea synthesis), and essential amino acids concentration is raise, utilize the catabolite of vivo acid--ammonia synthesis protein, thus liver, nephridial tissue urea synthesis are reduced; On the other hand, Radix Et Rhizoma Rhei also suppresses the decomposition of body protein, with the content of minimizing blood urea nitrogen and creatinine, and the drainage of the creatinine of promotion carbamide.

(15) antiinflammatory action: Radix Et Rhizoma Rhei has the obvious suppression effect to multiple zoopery inflammation, and oral decoct can significantly suppress Oleum Tiglii and cause mice ear inflammatory edema, rat formaldehyde, Ovum Gallus domesticus album pedal swelling, the granuloma induced by implantation of cotton pellets hypertrophy of mice and rat.Rheum hotaoense C. Y. Cheng et C. T. Kao extractum all has significant inhibitory effect to rat Ovum Gallus domesticus album and formaldehyde pedal swelling and mouse experiment peritonitis.

(16) analgesic cooling effect: after gavaging the Radix Et Rhizoma Rhei water decoction for the rabbit of normal and Diplococcus pneumoniae infectious fever, observe pathologic fever in rabbit body temperature (anus temperature) and obviously descend, simultaneously as seen in the ventriculus tertius perfusate PGE content obviously reduce.Radix Et Rhizoma Rhei may be brought into play cooling effect by influencing PGE.

(17) anti-aging effects: the rheum rhabarbarum polysaccharide that extracts in the rheum rhabarbarum can obviously prolong average life and the maximum life span of both sexes fruit bat.

The rheum rhabarbarum polysaccharide also can increase swimming time and the oxygen-resistant ability of 2-3 monthly age mice, shows that the rheum rhabarbarum polysaccharide has multiple effects such as strong.

(18) to the influence of diabetes: the type rat drug resistance to insulin disappearance that Radix Et Rhizoma Rhei can make streptozotocin cause, ERYTHROCYTE INSULIN maximum combined power raises, and serum insulin levels reduces.Radix Et Rhizoma Rhei has similar effect to alloxan diabetes rats.The Insulin receptor INSR adhesion be can improve, sugar, lipoidosis and hyperinsulinemia improved.Illustrating that acceptor binding force reduces and the information conductive impairment is the basis of development of insulin resistance, show that Radix Et Rhizoma Rhei is at acceptor levels treatment NIDDM, is the atherosclerotic ideal medicament of prevent diabetes.

(19) estrogen-like effects: emodin has estrogen-like effects, can make the rapid restorative cycle of castration female rats, and clinic trial also has the effect of estrone sample.

(20) diuresis: Radix Et Rhizoma Rhei crude drug and chrysophanic acid, emodin all have diuresis.

(21) physiological disposition:

1. absorb to adopt the absorption of isotope-labelling method research emodin, the single oral dose emodin, radioactivity increases sharply in the PBF, reaches maximum in 2 hours, then drops to peakedly 30% in 24 hours, then slowly descends later on.

2. after the rhubarb anthraquinone that distributes absorbs, serve as maximum with liver, kidney, gallbladder in vivo, isotope-labelling method proves that emodin mainly is distributed in kidney, mesentery and the fat, in muscle, brain, small intestinal and the colon seldom.

3. draining rhubarb anthraquinone and discharged by excrement and urine, account for 23.4% and 22.8% of intake respectively, served as at most through the urine discharge with 2-4 hour, discharged about 61% in 8 hours.

(22) toxic and side effects:

1. acute toxicity Radix Et Rhizoma Rhei ether extract mouse peritoneal injection, dosage reaches 40g (crude drug)/kg, observes 72 hours, does not see dead and unusual.Rhubarb preparation mouse subcutaneous injection LD50 is 4.052g/kg and 2g/kg.With age, CPC was every group of 6 lumbar injections of mice all around, the about 0.25-0.5g/kg of LD50 of the Diluted Alcohol extractum of continuous stricture of vagina Radix Et Rhizoma Rhei, Rheum tanguticum, second-class Rheum tanguticum; The Rheum tanguticum decoction pieces, etc. the about 0.25g/kg of LD50 of outer Radix Et Rhizoma Rhei; Japan's Radix Et Rhizoma Rhei, Turkey's Radix Et Rhizoma Rhei, the about 1.25-2.5g/kg of roundleaf Radix Et Rhizoma Rhei; It is generally acknowledged that the Radix Et Rhizoma Rhei oral toxicity is injected little.

The LD50 of Radix Et Rhizoma Rhei anthraquinone analog derivative mouse stomach, emodin are that 0.56g/kg, physcione are 1.15g/kg, and chrysophanol is 10g/Kg.

2. long term toxicity:

To gastrointestinal influence with 200% Radix Et Rhizoma Rheidecocted solution filling stomach rat, every day 3-4.5ml, scanning electron microscopic observation has the different irritable inflammation of degree to its harmonization of the stomach large intestine after 4,5 days, thinks that this is to cause indigestion and loss of appetite, diarrheal reason.

Have the report Radix Et Rhizoma Rhei to irritate " deficiency syndrome " rat due to the stomach to the immunologic function inhibitory action, immune organs such as thymus, spleen, mesenteric lymph node diminish, alleviate, and also cause the obvious atrophy of thymus in mice, Golden Hamster.

The Radix Et Rhizoma Rhei that influences to reproductive system was irritated the stomach rat 7.5g/kg14 days, and visible female Mus period of sexual maturity obviously delays, and uterus, ovary weight alleviate.

The Radix Glycyrrhizae pharmacological action

1. hepatoprotective effect: glycyrrhizic acid can make the rabbit of the total biliary pore of ligation, the hemobilirubin of rat reduce, and urobilinogen is drained to be increased, and this effect is stronger than Glucuronic acid lactone or methionine.Use the ductus choledochus method, glycyrrhizic acid can obviously increase the biliary secretion of rabbit.Discover that chronic active hepatitis patient's macrophage (M) phagocytic function can return to normal level after glycyrrhizic acid (CL) treatment, and after glycyrrhizic acid (non-CL) treatment, still is starkly lower than normal.Clinical dynamic observation result shows that the GL group all returns to higher level inside and outside treatment M phagocytic rate in mid-term is stopped.Only be 1/3 of non-GL group the course of treatment of GL group, the normal required short treating period of liver function recovery, effective percentage height.Think that it may be one of its treatment chronic active hepatitis effective mechanism that GL improves the effect of M phagocytic function.Glycyrrhizic acid shows that to the experiment of carbon tetrachloride acute liver damage influence mouse peritoneal injection 75 or 150mg/kg all can resist the acute poisoning effect of carbon tetrachloride to liver.The glycyrrhizic acid that studies show that of the effect of the experimental liver cirrhosis of glycyrrhizic acid control rat can obviously stop the rising of carbon tetrachloride poisoning rat SGPT vigor, can reduce accumulating of the interior triglyceride of liver.Histopathology is observed and is found, its hepatic injury of rat for the treatment of through glycyrrhizic acid is light than matched group.The serum tire first globulin recall rate of glycyrrhizic acid group also is higher than matched group.

2. Detoxication: mouse experiment finds that glycyrrhizic acid has significantly Detoxication to the toxicity of chloral hydrate, strychnine, urethane and cocaine, arsenobenzene, mercuric chloride etc.; Detoxication to cocculin, caffeine, acetylcholine, pilocarpine, nicotine, barbiturates etc. is taken second place; Then invalid to atropine, sulfonal (Sulfanal), physostigmine, morphine, antimony agent, ephedrine and epinephrine are slightly increased its toxicity on the contrary.Glycyrrhizic acid has detoxicating adhesive to tetrodotoxin, TTX, snake venom, can prevent the lethal effect and the local necrosis effect of snake venom with the snake venom hybrid injection in white mice, and its effectiveness is higher than calmette's serum.The Radix Glycyrrhizae soap can also be removed the lethal effect of diphtheria toxin, diphtherotoxin, tetanus toxin.The agent of Radix Glycyrrhizae silks cooperates anticarcinogen camptothecine, monocrotalinum etc. to share, and has the detoxifcation potentiation, can significantly resist camptothecine toxicity and strengthen its curative effect as ammonium glycyrrhizinate.Glycyrrhizic acid can protect erythrocyte to avoid the dissolving of Saponin in external hemolytic experiment as a kind of non-hemolytic Saponin, has the hemolytic Detoxication of antagonism Saponin.This Detoxication may be the adsorption by glycyrrhizic acid.Also the someone thinks that glycyrrhizic acid absorbs the back and be decomposed into enoxolone and glucuronic acid in liver, and the latter can combine with poisonous substance and detoxify.

3. the anti-immunization of antiinflammatory: glycyrrhizic acid has the antiinflammatory action of Phenylbutazone or hydrocortisone sample.The rat experiment arthritis that the glycyrrhizic acid on Carrageenan causes has inhibitory action.Glycyrrhizic acid 50mg/Kg lumbar injection can suppress the Cavia porcellus anaphylaxis due to the Ovum Gallus domesticus album.Glycyrrhizic acid can suppress the mast cell degranulation that histamine liberators-compound 48/80 causes when 0.46mM concentration, thereby has stoped the release of crossing sensitive media.Mice carries out immunity with-amylase that bacillus subtilis produces, measure in the different time antibody titer in the blood later on respectively, find that the every Mus of cortisone 1mg every day abdomen control injection can suppress production of antibodies, and every day every Mus glycyrrhizic acid 4mg lumbar injection, continuous 15d, antagonist produce does not have influence.

Mice iv glycyrrhizic acid 25 or 50mg/kg can significantly suppress passive cutaneous anaphylaxis, PCA, and can antagonism histamine, acetylcholine and irritated slow reacting substance (SRS-A) to the exsomatize contraction of ileum and guinea-pig isolated trachea of rabbit, more than effect all increases with dosage.Glycyrrhizic acid makes that the spleen of mice is heavy, thymus is heavy obviously increases; Can make total white blood cells, especially neutrophilia and mononuclear cell number obviously increase.Glycyrrhizic acid has the effect of regulating body's immunity.There is report to sum up glycyrrhizic acid to using human IgG immune balb/c mice splenocyte in the synthetic influence of external antibody.To add in the lymphocyte culture,, detect antibody growing amount in the supernatant with the ELISA method behind the 72h respectively at 24,48.The result shows that (1 * 10-7,4 * 10-7mg/ml) all can obviously suppress the synthetic, especially remarkable with the 3rd day of lymphocyte antibody to the glycyrrhizic acid of variable concentrations.By the method for lactic acid dehydrogenase release test, in the external test ammonium glycyrrhizinate to the active influence of BALB/C mice natural killer cell (NK cell).Experimental result shows with normal control to be compared, and (1 * 10-7-1 * 10-1mg/ml0, the NK cells in mice activity all has significant enhancing to the ammonium glycyrrhizinate of adding variable concentrations, proves that thus ammonium glycyrrhizinate has important regulating action to body's immunological function.Give oral 7 days of mice continuously with ammonium glycyrrhizinate, zinc glycyrrhizate 25mg/kgd and 50mg/kgd, make the low immunologic function of mice that causes by cyclophosphamide recover normal; Increase increases the formation that the immunologic opsonin Flos Rosae Rugosae forms cell (SRF-C) number and serum hemolysin (HC50) to the function of cleaning up of carbon granules; To the no effect of delayed hypersensitivity (DTH).The result proposes, and ammonium glycyrrhizinate, zinc glycyrrhizate promptly are mainly the effect of glycyrrhizic acid improving aspect body non-specific immunity and the humoral immunization ability and zero difference, and zinc is like no effect.

4. 17-hydroxy-11-dehydrocorticosterone sample effect:

(1) glucocorticoid sample effect: low dose of glycyrrhizic acid (600mog/kg) lumbar injection can make the rat chest gland atrophy and the increase of adrenal gland's weight, and showing has the effect of corticotropin sample.The light disease Addison's disease people of intramuscular injection every day 12.5mg cortisone, from measuring the 3rd day that urinates corticosterone, day after day and with glycyrrhizic acid 160mg intramuscular injection, the result urinates that the release 17-hydroxycorticosterone in middle reaches increases and conjunction type 17 1 hydroxycorticosterones all reduce, but the total excretion no change.The continuous intramuscular injection glycyrrhizic acid of healthy people 80mg, respectively once, the result is also similar sooner or later, and only total 17-hydroxycorticosterone value has the tendency of reduction slightly.Illustrate that glycyrrhizic acid can strengthen and prolong the effect of cortisone.Its mechanism of action may be that glycyrrhizic acid inhibition cortical hormone have destruction or minimizing and protein bound in the body, makes free 17-hydroxy-11-dehydrocorticosterone concentration rising in the blood, thereby strengthens its effect.

(2) mineralocorticoid sample effect: the sodium salt of glycyrrhizic acid or ammonium salt all have the effect of desoxycortone sample, and the discharge of kinds of experiments animal urine amount and sodium is reduced, and potassium is discharged to be increased, blood sodium rises, blood calcium reduces, the atrophy of adrenal cortex spherical zone shape, and cortisone can strengthen its effect in a small amount.Cause false aldosteronism, quadriplegia and hypokalemia behind a large amount of use glycyrrhizic acids.

5. antiulcer action: the rat chronic ulcer that Dichlorodiphenyl Acetate brings out, the cure rate of oral glycyrrhizic acid are 47.7%, not only can suppress its gastric acid secretion, and the soup healing also can promote to burst.

6. antitumor action: glycyrrhizic acid can produce morphologic variation to rat ascites hepatocarcinoma and mice ehrlich ascites cell, glycyrrhizic acid still can suppress the yoshida sarcoma that subcutaneous injection is transplanted, and can also prevent that polyoxy biphenyl from also can prevent the caused hepatocarcinoma of 0.06% 4 a basic ammonia diphenyl diimide to the hepatocarcinoma that male mice caused.Its mono-ammonium has inhibitory action to mice ehrlich carcinoma and sarcoma.Its mono-ammonium has inhibitory action to mice ehrlich carcinoma and sarcoma.Its anticancer mechanism it be not immediately clear, finds that the glycyrrhizic acid pair cell has good repair when using the mouse liver cell ultrastructure morphologic observation of glycyrrhizic acid.Sharply reduce the transaminase (GOT and GPT) that can make gallbladder emiocytosis to glycyrrhizic acid clinically.Thereby think that glycyrrhizic acid can strengthen the Detoxication and the resistance of cell.

7. to the influence of lipid metabolism: after most of hypertensive patient took glycyrrhizic acid, serum ornitrol descended, the also corresponding reduction of blood pressure.Glycyrrhizic acid 10mg/kg every day intramuscular injection, 5d has tangible effect for reducing fat to experimental rabbit hyperlipemia continuously.Low dose of glycyrrhizic acid (2mg/d) can make the cholesterolemia of experimental atherosclerosis rabbit reduce within a certain period of time, atherosis degree alleviates, 20mg/d can stop large artery trunks and crown development of atherosclerosis, share with estrogen, this effect can strengthen, but dosage when bigger (40mg/d) invalid on the contrary.Use 5mg/Kg, the experimental atherosclerosis rabbit only had slight norcholesterol effect, share, there is no therapeutic effect with two chlorine gram urine thiophenes, its potassium salt 15mg/kg effect for reducing fat then extremely a little less than.Someone thinks that this effect of glycyrrhizic acid is relevant with stimulation hypophysis one adrenal system, or glycyrrhizic acid can promote the combination and drainage of cholesterol.

8. to the influence of urinary system, reproductive system: glycyrrhizic acid has antidiuretic activity to rat, is accompanied by the sodium output to reduce, and the potassium output also slightly reduces.To adrenalectomized rat, glycyrrhizic acid still can make the discharge of sodium and potassium reduce, and illustrates what this effect realized by adrenocortical hormone.Glycyrrhizic acid and sodium salt thereof, intravenous injection can strengthen the diuresis of theophylline, and Dichlorodiphenyl Acetate potassium does not then have influence, can suppress the accretion of estrogen to teenage animal uterus, still has same purpose behind excision adrenal gland or the ovary.When glycyrrhizic acid dosage increases, then instead can strengthen estrogen-like effects.

9. refrigeration function: glycyrrhizic acid has refrigeration function to the rat of heating and mice and rabbit.To erythrocyte membrane Na+, the inhibitory action of K+-ATPase.When glycyrrhizic acid was 4 * 10-3 and 4 * 10-2mg/ml at working concentration, to rabbit erythrocyte film Na+, K+-ATPase produced the obvious suppression effect.Drug level during its 50% suppression ratio is 14.6 ± 0.9 g/ml.Inhibitory action is competition-non-competing type and mixes inhibition.The Ki value that records under this experiment condition is 2.2ng/ml.

10.r-interferon urgees to induce effect: glycyrrhizic acid shows the experiment that human spleen cell produces the influence of r-interferon (r-IFN): ConA and PHA all can induce human spleen cell to produce IFN, glycyrrhizic acid can improve the IFN level that ConA induces human spleen cell to produce, but the IFN level that PHA induces is not influenced; It is 200 g/ml that glycyrrhizic acid increases the optimum concentration that ConA induces IFN to produce, and the suitableeest to induce the time be 48h, and cell concentration is advisable with 1 * 107/ml.The IFN that glycyrrhizic acid and ConA combined induction human spleen cell produce is based on the r type.

Laboratory observation glycyrrhizic acid (CL) influence that umbilical cord blood mononuclear cell (CBMC) produced r-interferon (IFN γ).The result shows: GL can obviously improve concanavalin A, Con A (ConA) and induce neonate CBMC to produce the level of (IFN γ), and its suitableeest activity is 100 g/ml under this experiment condition.Obviously be better than the effect that both act on generation simultaneously if GL acts on its effect that improves IFN of CBMC prior to ConA12h, and can partly reverse hydrocortisone and suppress the effect that CBMC produces IFN γ.Results suggest GL might be used in clinical medicine as the control infant infection, and might alleviate the immunosuppressive effect that causes by using glucocorticoid with GL.

11. the synthetic influence of DNA to In vitro culture lymph prostaglandin: the monoammonium glycyrrhizinate of having measured variable concentrations mixes the synthetic influence of suppression ratio and PGI2 and TXA2 to the 3H thymidine (3HTdR) of In vitro culture people and rat lymphocyte.The result shows: monoammonium glycyrrhizinate increases 3HTdR and mixes suppression ratio when 1.5 * 10-7 and 3 * 10-7.Utilize the RIA method to measure the influence of monoammonium glycyrrhizinate, find that 4 * 10-8 under the effect of 4 * 10-11mol/L monoammonium glycyrrhizinate, can significantly reduce the release of TXA2, and the release of PGI2 is not made significant difference at 4 * 10-7 lymphocyte PGI2 and TXA2.

12. glycyrrhizic acid can also make rat blood pressure raise; Its sodium salt can make rabbits blood pressure rise, but tip blood vessel is not had influence, does not also have haemolysis.

13. toxic action: the MLD of glycyrrhizic acid mouse subcutaneous injection is 1g/kg.Glycyrrhizic acid heavy dose (20-30mg/kg is more than continuous 1 week) can cause edema, but can disappear after the drug withdrawal.

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 of cardiovascular and cerebrovascularinfarction district cell, 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, cerebrovascular atherosclerosis, 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 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, the immune stimulatory globulin and production of antibodies.Strengthen the ability of body resistance disease, make machine stop each organ and 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. the prevention and the therapeutical effect of the cardio cerebrovascular affection that diabetes are caused.Scarce selenium can make lipid catabolism unusual; Bring out ketoboidies generation-diabetes ketosis, ketoboidies ↑+albuminolysis-bupropion metabolite product ↑-PH ↓-acidosis-diabetic ketoacidosis, selenium supplement can suppress diabetes ketosis and diabetes acidosis.

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

The effect of chromium and purposes (chromium trichloride)

1. trivalent chromium is a glucose tolerance factor:

(1) human body lacks chromium and can cause carbohydrate tolerance impaired or develop into diabetes, hyperlipemia, atherosclerosis, growth promoter and stagnate and the lost of life, and chromium supplement can reverse above-mentioned phenomenon.

(2) formation complex on three New Year's Day between chromium, insulin and the DNA mitochondrial DNA promotes that insulin plays a role-blood sugar lowering.

(3) chromium is normal glycometabolic necessary dimension secondary element, and chromium deficiency is relevant with type in the diet.(4) trivalent chromium is relevant with insulin active, lacks the chromium insulin active and reduces--and cause diabetes, hyperlipemia, atherosclerosis occurs.

2. chromium is to glycometabolic influence: high chromium raising rat and monkey, blood glucose, glycerol, three fat, cholesterol all significantly descend, blood glucose in diabetic rats decline 14-29%, the foreign data report: six routine diabetes patients, hyperglycemia takes place to lose weight, movement disorder, peripheral neuropathy takes place, through supply every day chromium 250 μ g, 2 weeks of logotype, without islets of langerhans small island element, patient's carbohydrate tolerance and function of nervous system are restored.Thereafter, supply every day 20 μ g chromium, carbohydrate metabolism can be kept normally.Clinical trial certificate: chromium supplement or GTF (the carbohydrate tolerance factor) can improve diabetes patient's impaired glucose tolerance person's glucose tolerance, and lowering blood sugar and blood fat improves insulin sensitivity, has increased insulin bioactivity.After the old people of people to 76 routine impaired glucose tolerance arranged again, from diet, supply with chromium 200 μ g every day, its carbohydrate tolerance is carried out the double blinding crossing research, three months is a course of treatment, carbohydrate tolerance sufferer as a result, chromium supplement carbohydrate tolerance therebetween obviously improves, and the comfort group does not have this effect.

3. replenishing of chromium reaches toxicological study:

(1) foreign scholar obtains promising result for the trivalent chromium of the additional 100-200 μ g of people that lacks chromium with the beer yeast of inorganic form or GTF and the high chromium yeast of artificial culture.

(2) chromium has the necessarily property accumulated in vivo, and biological half-life is 27 days, and the toxicity of chromium and existence have very big relation, and the trivalent chromium chemical property is torpescence very, and toxicity is extremely low, and difficulty causes poisoning.

(3) clinical trial: chromium trichloride and chromium acetate difference 0.8mg/kg and 2.29mg/kg give mice, do not see toxicity.Chromium trichloride is oral to be 1870mg/kg to rat LD50, mouse peritoneal injection LD50 is 140mg/kg, having the human chromium trichloride that Mus is carried out iV injection LD50 is 10mg/kg, more than like this zoopery be to be used for the treatment of anti-unusual tens thousand of times of diabetes and sugar, as seen very wide safety range is arranged therebetween.Have human to contain the drinking-water raising rat 1 year of trivalent chromium 25mg/L, do not see liver is arranged, the kidney aspect damages and toxicity, serve on three months with the water of 50-1000mg/L for cat, do not see toxic reaction.

(4) the mutagenic research of chromium trichloride: have only when heavy dose of Chlorizate chromium 29mg/kg mouse peritoneal is injected, certain teratogenesis is just arranged.For trivalent chromium whether carcinogenesis is arranged, do not appear in the newspapers as yet.Therefore only give oral trivalent chromium, safety range is quite wide.Replenish 50-200 μ g every day and can not cause toxic reaction.

4. modern clinical practice: 250 μ g/ days of chromium trichloride serve on 10, change for 25 μ g/ days into after blood sugar urinary sugar is normal, and patient's carbohydrate tolerance and nerve are restored, and later 25 μ g/ day carbohydrate metabolism can be kept normally.

The effect of manganese and purposes

1. manganese is arginase, RNA polymerase, and the composition of superoxide dismutase etc., and can activate some enzymes, and as: carboxylases etc. play an important role to endocrine regulation and immunologic function adjusting.

2. manganese can make the neural blood vessel wall loose, reaches the blood vessel dilating effect, promotes the heart, brain, kidney and the blood supply of dimension blood vessel circulation, and the control heart, brain, renal vascular disease become and dimension vascular lesion and various nerve injury.

3. manganese deficiency pancreas hypoplasia, insulin secretion reduces, and blood glucose increases, and causes diabetes.

4. manganese deficiency can cause the skeleton pathological changes, osteodystrophy, and rheumatoid and rheumatic arthritis, osteoarticular injury, degeneration, the sclerotin paraplasm damages simultaneously for flesh and blood pipe and nerve, quickens osteopathia damage process and osteonecrosis etc.

5. anemia appears in child's manganese deficiency, and monster appears in the anemia of pregnant woman, the congenital anomaly of skeletal bone pathological changes.

6. manganese deficiency can cause the manganese enzymatic activity to reduce, the endocrine disturbance, and immunologic hypofunction also infects multiple infectious disease.

7. manganese can impel people's slow down aging, and longevity has the effect of the free radical of removing.

8. consumption, feed ration 5-10mg.

The effect of zinc and purposes (zinc sulfate)

1. it is synthetic that zinc participates in interior 80 plurality of enzymes of body, and pancreas, gonad, activity pituitary all have zinc to participate in.

2. keep the normal development function of male's gland, zinc deficiency can make oligospermia, and impotence generandi forms male sterility.

3. the human body barriers function can be kept and strengthen to zinc, performance defence infection effect.

4. 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.

5. 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 abdomen etc.

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

7. feed ration: 10-15mg/ day, maximum 120mg/ day.

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

This hepatitis restoration curing capsule, its prescription consist of schizandrin selenium Herba Sophorae alopecuroidis alkali manganese, emodin chromium, zinc glycyrrhizate.

(3) Radix Et Rhizoma Rhei extracts the emodin chromium process:

(4) Radix Glycyrrhizae is extracted zinc glycyrrhizate technology:

(5) select the best safety consumption for use

Schizandrin selenium 3mg/kg/ day;

Herba Sophorae alopecuroidis alkali manganese 10mg/kg/ day;

Emodin chromium 40mg/kg/ day;

Zinc glycyrrhizate 5mg/kg/ day;

Amount to daily 2900mg/50kg/ day;

Be divided into and adorn 6 large size capsules, each contains 0.483g.

Medicine is for power: Radix Et Rhizoma Rhei glycoside oral absorption is good, effect time of origin 30 minutes, and 6-19 hour both defecation after the medication rushes down down that composition mainly is the Senna fruit glycoside, finds that liver sausage concentration is higher.

Claims

1. a hepatitis restoration curing capsule is characterized in that prescription consists of schizandrin selenium Herba Sophorae alopecuroidis alkali manganese, emodin chromium, zinc glycyrrhizate.

2. capsular preparation technology of medicine " Ganyanfukangling " for curing hepatitis, concrete steps are:

(3) Radix Et Rhizoma Rhei extracts the emodin chromium process:

(4) Radix Glycyrrhizae is extracted zinc glycyrrhizate technology:

(5) select the best safety consumption for use

Schizandrin selenium 3mg/kg/ day;

Herba Sophorae alopecuroidis alkali manganese 10mg/kg/ day;

Emodin chromium 40mg/kg/ day;

Zinc glycyrrhizate 5mg/kg/ day;

Amount to daily 2900mg/50kg/ day;

Be divided into and adorn 6 large size capsules, each contains 0.483g.