CN103142937A - Medicament for treating hepatitis and preparation method thereof - Google Patents

Abstract

The invention provides a medicament for treating hepatitis and a preparation method thereof. The medicament is mainly prepared from saururus chinens, herba hyperici japonica, chrysosplenium, poria cocos, radix scutellariae, radix curcumae, radix curcuma, herba epimedii and cassia twig, and is mainly used for treating acute jaundice and non-icteric hepatitis as well as persistent hepatitis and chronic hepatitis. Pharmaceutical dosage forms include tablets, granules, hard capsules, soft capsules, pills and drop pills.

Description

A kind of medicine for the treatment of hepatitis and preparation method thereof

Technical field

The present invention relates to a kind of acute jaundice and anicteric hepatitis of being used for the treatment of, medicine of delay property, chronic hepatitis and preparation method thereof belongs to the Chinese herbal and crude drugs preparations technical field.

Background technology

Our country is a hepatitis big country, the high Endemic Area of hepatitis B particularly, according to we at end of the seventies and the beginning of the nineties twice national hepatitis the data show of Epidemiological study, the people that our country infected hepatitis B virus probably has seven hundred million nearly, 6.9 hundred million people infected hepatitis B virus, infection rate is 57.6%, the whole nation has the people of long-term Hepatitis B carrier to have 1.2 hundred million, the carrying rate of hepatitis B virus surface antigen is 9.75%, accumulate over the years, existing chronic hepatitis B people probably has more than 2,000 ten thousand.Hepatitis B distributes very extensive, and there is infection morbidity in various degree in our each province of the whole nation.In recent years, the control of chronic viral hepatitis, hepatitis interstitialis chronica and primary hepatocarcinoma has accounted for very large proportion in clinical liver disease and research.Up to now, China is still one of this three large disease in the world area the most occurred frequently, and Hepatitis B Virus Infection has surpassed 100,000,000 people.

The cause of disease or the pathogenesis of a lot of hepatic disease are not yet fully clear so far, and the most medicines that are used for clinically hepatic disease only have the ashamed use of auxiliary treatment, still belong to symptomatic treatment, and wherein the curative effect of some medicine awaits to estimate.Treatment is conceived on the one hand protection and nourishes hepatocyte, in the hope of recover hepatocellular vigor and function as far as possible, wishes on the other hand to reduce hamartoplasia, prevents liver cirrhosis.About over one hundred kind of the medicine for the treatment of hepatic disease can be categorized as by its pharmacological action: the hepatitis virus resisting medicine, mainly suppress copying of hepatitis B virus; Hepatoprotective, the hepatic of commonly using clinically at present has vitamins, promotes the medicine of liver detoxification, promotes the medicine of energy metabolism, and the medicine of promotion protein synthesis and lipotropic medicine etc. are multiple.But generally speaking, at present still without specific medicament.because domestic hepatites virus infections person generally lacks relevant knowledge, add that domestic present medical market is very chaotic, cause domestic have a large amount of hepatites virus infections persons especially HBV the infected when not needing special treatment, blindly accept so-called " liver protecting therapy ", wherein again take Chinese patent medicine as many, these Chinese patent medicines are many without the approval of national Bureau of Drugs Supervision, whether toxic side effect is still not clear, often can increase the burden of liver, liver function injury is further increased the weight of, simultaneously, in recent years, along with being on the increase of medicament categories, cause the also corresponding increase of medicine of liver injury.Therefore, drug induced hepatic injury has become clinical more common and easily produce the drug-induced disease of serious consequence.Medicamentous liver lesion is the common cause that causes abnormal liver function.

Classical prescription in motherland's medical science, proved recipe also day by day come into one's own to the special efficacy of hepatitis.Compare with western medicine and medical practitioners, Chinese medicine has the dialectical advantage of its uniqueness, and the Chinese medicine side effect is little, is good at many target spots integrally-regulated at many levels, and the Comprehensive Treatment effect is strong, and is cheap, more and more is subject to the recognition and acceptance of more hepatitis.The present invention has researched and developed the tool clearing away heat-damp and promoting diuresis, soothing liver-QI for relieving depression, blood stasis dispelling jaundice eliminating, the new medicine of function of gallbladder promoting spleen invigorating effect in conjunction with the achievement in research of modern Chinese medicine treatment hepatitis.For hepatitis provides safety, efficient medicine, control and mitigation symptoms, improved Quality of Life.To expect to benefit more vast hepatitis.

Summary of the invention

The object of the present invention is to provide a kind of medicine for the treatment of hepatitis evident in efficacy.

Medicine of the present invention is comprised of the nine flavor medical materials such as Rhizoma Saururi (Herba Saururi), Herba Hyperici Japonici, Chrysosplenium nudicaule Bunge, Poria, Radix Scutellariae, has clearing away heat-damp and promoting diuresis, soothing liver-QI for relieving depression, blood stasis dispelling jaundice eliminating, the effect of function of gallbladder promoting spleen invigorating.Be used for acute jaundice and anicteric hepatitis, delay property, chronic hepatitis etc.We have used for many years clinically, and it is evident in efficacy.In the present invention, Rhizoma Saururi (Herba Saururi), Herba Hyperici Japonici and Components In Scutellaria Baicalensis are all take flavonoid as main, and the Herba Hyperici Japonici injection main constituent of clinical middle application is flavones ingredient; In Radix Scutellariae, main effective ingredient content of baicalin is very high, and the pharmacological action that protects the liver is clearer and more definite at present; The flavonoid glycoside of main effective ingredient take Quercetin as aglycon of Rhizoma Saururi (Herba Saururi) is main constituent, and lignanoid, hydrolysable tannin constituents etc. are still arranged, therefore draft polysaccharide, the sterols composition that extracts in total flavones and Poria, the formulation applications such as granulation, drop pill are in clinical.Technique of the present invention is advanced, and clinical application weight in kind obviously reduces.Can reach " triple effect " (efficient, quick-acting, long-acting), the requirement of " three is little " (dosage is little, toxicity is little, side effect little) and " five convenience " (produce, transport, preserve, carry, easy to use) is one for hepatitis and better selects.

Medicine of the present invention is made by the crude drug that comprises following parts by weight ratio:

Rhizoma Saururi (Herba Saururi) 300-600 part Herba Hyperici Japonici 200-500 part Chrysosplenium nudicaule Bunge 200-500 part

Poria 100-300 part Radix Scutellariae 100-300 part Radix Curcumae 100-300 part

Rhizoma Curcumae Longae 100-300 part Herba Epimedii 100-200 part Ramulus Cinnamomi 100-200 part.

The raw material medicines in portions by weight ratio that medicine of the present invention comprises be preferably:

Rhizoma Saururi (Herba Saururi) 400-500 part Herba Hyperici Japonici 300-400 part Chrysosplenium nudicaule Bunge 300-400 part

Poria 200-300 part Radix Scutellariae 200-300 part Radix Curcumae 200-300 part

Rhizoma Curcumae Longae 200-250 part Herba Epimedii 150-200 part Ramulus Cinnamomi 150-200 part.

Also be preferably:

350 parts of 350 parts of Chrysosplenium nudicaule Bunges of 450 portions of Herba Hyperici Japonici of Rhizoma Saururi (Herba Saururi)

260 parts of 260 portions of Radix Curcumaes of 260 parts of Radix Scutellariaes of Poria

180 parts of 180 parts of Ramulus Cinnamomi of 260 parts of Herba Epimedii of Rhizoma Curcumae Longae.

Also be preferably:

500 parts of 500 parts of Chrysosplenium nudicaule Bunges of 600 portions of Herba Hyperici Japonici of Rhizoma Saururi (Herba Saururi)

200 parts of 200 portions of Radix Curcumaes of 200 parts of Radix Scutellariaes of Poria

180 parts of 180 parts of Ramulus Cinnamomi of 200 parts of Herba Epimedii of Rhizoma Curcumae Longae.

Chinese medicine preferred for this invention can be had the Chinese medicine of same or similar effect to replace, and these medical materials all can be according to " method of the records such as Chinese pharmacopoeia, " national Chinese medicine processing standard ", " Chinese medicine voluminous dictionary " is concocted, and the curative effect of medication of the present invention of the medical material preparation after the process of preparing Chinese medicine is identical.

Medicine of the present invention can also adopt the application process of Chinese medicine, as fries in shallow oil soup and take, and is ground to loose swallowing or water delivery service, also can produce same curative effect.

The preparation formulation of medicine of the present invention is any one in tablet, granule, hard capsule, soft capsule, pill, drop pill, slow releasing tablet or controlled release tablet.

Another object of the present invention is to provide the preparation method of this medicine, and this medicine is made by the following step:

1) get Rhizoma Saururi (Herba Saururi), Herba Hyperici Japonici, Chrysosplenium nudicaule Bunge, Rhizoma Curcumae Longae and add 12 times of amount 70% ethanol, refluxed 3 hours, recovery ethanol is concentrated into approximately 1.1 clear paste of relative density, and is standby;

2) Poria, Radix Curcumae, Herba Epimedii, Ramulus Cinnamomi, Radix Scutellariae add 10 times of decoctings and boil twice, wherein Radix Scutellariae until water boil rear under, each 3 hours, merge medicinal liquid, concentrated, approximately 1.1 clear paste, standby;

4) with step 1) clear paste and 2) clear paste mix, add suitable pharmaceutically acceptable adjuvant, step is made tablet, granule, hard capsule, soft capsule, pill, drop pill, slow releasing tablet or controlled release tablet routinely.

Be the safety of proved invention medicine, the granule according to the preparation of the method for embodiment 1, carried out following experiment:

One, toxicity test

Below in conjunction with toxicological test data of the present invention, safety of the present invention is described.

1 acute toxicity testing

Can't measure LD50 through prerun, therefore carry out the maximum dosage-feeding test.get 40 of mices, male and female half and half, be divided at random two groups, every group 20, being respectively matched group and administration group. each organizes the equal fasting of mice 12 hours, then administration group mice suspension of the present invention (Cmax) gavage of 0.47g dry powder/ml, capacity is 0.4ml/10g body weight (heap(ed) capacity), be total to the administration secondary on the 1st, every minor tick 5 hours, dosage is 37.3g dry powder/kg, 242.6 times of quantity are equivalent to be grown up, control group mice waits the capacity distilled water, animal general state in 14 days after the observation administration, hair color, body weight, diet, movable, breathe, motion, reflection, eye inspection indication, cardiovascular indications, salivation, the indexs such as defecation change.

Result of the test: it is good that result is respectively organized mice general state in 14 days, and hair color is smooth, body weight gain, diet and movable no abnormality seen, the indexs such as breathing, motion, reflection, cardiovascular indications, salivation, defecation are all normal, and none death, do not find the overt toxicity reaction.

2. long term toxicity test:

This research has been carried out the rat chronic toxicity test of six months according to the pertinent regulations requirement of study of tcm new drug to the present invention.Observe and repeat continuously to give the toxic reaction that the present invention produces rat, the symptom and the order of severity that at first occur, the target organ of toxicity and recovery thereof and development are determined nontoxic amounts of reactants, provide reference for drafting the human safe dose.Animal is SD rat (cleaning level), route of administration is gastric infusion, adopts three dosage: low dose of (be equivalent to clinical application 15 times), middle dosage (be equivalent to clinical application 30 times), heavy dose of (be equivalent to clinical application 60 times).experimental period is 6 months, and convalescent period was 2 weeks, observation index comprises: general state is observed, body weight change, food-intake, hematological examination: prothrombin time (QuickShi one-step method), content of hemoglobin (HemoCue), red blood cell count(RBC) (microscopic method), reticulocyte count (microscopic method), numeration of leukocyte and classification (microscopic method), platelet count (microscopic method), 5) blood parameters: abdominal aortic blood, separation of serum, detect ALT (ALT, reitman-frankel method), aspartic acid aminotransferase (AST, King's method), alkali phosphatase (ALP, amino antipyrine is surveyed the phenol method), blood glucose (GLU, glucose oxidase method), total bilirubin (T-BIL, the caffeine method), blood urea nitrogen (BUN, diacetyl monoxime method), creatinine (Grea, picric acid method), total protein (TP, biuret method), albumin (ALB, the bromocresol green method), T-CHOL (T-CHO, o-phthalaldehyde method), serum potassium (K+), serum sodium (Na+), serum chloride (CL-), 6) organ coefficient: the heart, liver, spleen, lung, kidney, brain, adrenal gland, thymus, thyroid, epididymis, testis, ovary, uterus, 7) histological examination: each organizes the main organs such as the rat heart, liver, spleen, lung, kidney, brain, cerebellum, hypophysis, spinal cord, sciatic nerve, bone marrow, esophagus, stomach, small intestinal, large intestine, adrenal gland, thymus, thyroid, lymph node, bladder, ovary, uterus, testis, epididymis, prostate, the routine paraffin wax section, HE dyeing, Microscopic observation have or not toxic to change.Result shows, the present invention all has no significant effect the general status of rat, body weight, hematological indices, 13 biochemical indicators and Main Organ Coefficients; Each internal organs naked eyes and Microscopic observation are also without obvious pathological change.Show that this medicine reacts without overt toxicity, can recommend clinical use.

Two, clinical verification

The present invention is old docter of TCM clinical experience side, year accepts altogether outpatient service hepatitis person 296 examples for medical treatment from calendar year 2001 to 2009.Women's 182 examples wherein, male's 114 examples, the age between 28 to 62,43 years old mean age.

2. differential diagnosis in tcm standard:

Primary symptom: 1. 2. abdominal distention after meal or abdominal distention increase the weight of distending pain over the hypochondrium in the afternoon

3. inappetence, 4. loose stool or the time do when half congealed

Inferior disease: the 2. irritated irritability spiritlessness and sparing of words of sighing constantly of belch of 1. feeling sick,

3. pale tongue, stringy pulse or string are slow

Dialectical requirement: (1) all to be possessed three of main symptoms and is assertive evidence; (2) all possess 2 of main symptoms and time 1 person of card is assertive evidence.

Exclusion standard is got rid of alcoholic liver disease, drug intoxication, autoimmunity and Metabolic liver disease patient; Get rid of mistakes such as merging hepatocarcinoma, hepatic encephalopathy, cirrhotic ascites for tasting the hepatopathy patient; Get rid of the serious serious primary disease patient of the heart, brain, blood vessel, lung, kidney, endocrine and hemopoietic system; Get rid of psychotic, gestation or women breast-feeding their children, age more than 18 years old or over-65s person and those who are allergic to this drug.

The curative effect determinate standard recovery from illness: symptom, sign disappear or basic the disappearance, and liver function recovery is normal, and the disease integration reduces 〉=95%; Produce effects: symptom, sign are obviously improved, and the disease integration reduces 〉=70%; Effectively: symptom, sign all make moderate progress, and the disease integration reduces 〉=30%; Invalid: symptom, sign are without obvious improvement, even increase the weight of, the disease integration reduces less than 30%.(annotate: the disease integral and calculating is by the nimodipine method) curative effect refers to

Result is cured 175 examples altogether, accounts for 59.12%; Produce effects 101 examples account for 34.12%; Effective 8 examples account for 2.70%, and invalid 12 examples account for 4.05%.

The present invention derives from old docter of TCM's clinical experience side, reaches more than 95% through the clinical practice effective percentage.Prove according to theory of Chinese medical science, zoopery and clinical practice, the present invention has clearing away heat-damp and promoting diuresis, soothing liver-QI for relieving depression, the blood stasis dispelling jaundice eliminating, the effect of function of gallbladder promoting spleen invigorating, and without toxicity, can be used for clinical treatment acute jaundice and anicteric hepatitis, the persons such as delay property, chronic hepatitis.

Model case:

Zhang Huiling, the female, 32 years old, anorexia, weak, yellowish-brown simple and unadorned, the stool malt sugar of complexion, the County Hospital laboratory test report shows suffers from chronic hepatitis, take the described granule of embodiment 1 one day 2 times, each 2 bags, after two weeks, above-mentioned symptom fades away, cured in one month, chemical examination again, laboratory test report shows that liver function recovery is normal.

Wang Meixiu, the female, 37 years old, suffer from acute icterohepatitisshock, weak abdominal distention is obvious, the complexion jaundice.The mobility of thrombinogen is lower than 40%, and serum bilirubin and alaninyl transferring enzyme are high, and with the described Granules in Treating of embodiment 1 one day 2 times, each 2 bags, after first quarter moon, weak symptom disappears substantially, and abdominal distention obviously alleviates, and has rosy cheeks.After medication one month, the mobility of thrombinogen, serum bilirubin and alaninyl transferring enzyme all recover normal value, nothing recurrence after curing.

Chen Mancang, the man, 51 years old, distending pain over the hypochondrium had vomiting and diarrhoea between appetite descends also, even be unable to leave the bed, with the described drop pill continued treatment of embodiment 2, one day twice, one time 10 balls.After two weeks, spirit takes a turn for the better, and after one month, the state of an illness is obviously suppressed, and can do some daily housework, recovers as ordinary person after two months, cures after March, follows up a case by regular visits to not recurrence in 3 years.

The specific embodiment

Following embodiment is used for illustrating the preparation of medicine of the present invention, but it can not consist of any restriction to scope of the present invention.

Embodiment 1

The preparation of medicinal granule of the present invention

Prescription:

Rhizoma Saururi (Herba Saururi) 600g Herba Hyperici Japonici 500g Chrysosplenium nudicaule Bunge 500g

Poria 200g Radix Scutellariae 200g Radix Curcumae 200g

Rhizoma Curcumae Longae 200g Herba Epimedii 180g Ramulus Cinnamomi 180g.

Preparation method:

1) get Rhizoma Saururi (Herba Saururi), Herba Hyperici Japonici, Chrysosplenium nudicaule Bunge, Rhizoma Curcumae Longae and add 12 times of amount 70% ethanol, refluxed 3 hours, recovery ethanol is concentrated into approximately 1.1 clear paste of relative density, and is standby;

2) Poria, Radix Curcumae, Herba Epimedii, Ramulus Cinnamomi, Radix Scutellariae add 10 times of decoctings and boil twice, wherein Radix Scutellariae until water boil rear under, each 3 hours, merge medicinal liquid, concentrated, approximately 1.1 clear paste, standby;

4) with step 1) clear paste and 2) clear paste mix, add proper starch; Drying is made 1000 gram granules.

5) packing is encapsulated as 400 bags and get final product with above-mentioned granule.

Embodiment 2

The preparation of medicament dropping pill of the present invention

Prescription:

Rhizoma Saururi (Herba Saururi) 300g Herba Hyperici Japonici 200g Chrysosplenium nudicaule Bunge 200g

Poria 120g Radix Scutellariae 150g Radix Curcumae 100g

Rhizoma Curcumae Longae 100g Herba Epimedii 150g Ramulus Cinnamomi 150g.

Preparation method:

1) get Rhizoma Saururi (Herba Saururi), Herba Hyperici Japonici, Chrysosplenium nudicaule Bunge, Rhizoma Curcumae Longae and add 12 times of amount 70% ethanol, refluxed 3 hours, recovery ethanol is concentrated into approximately 1.1 clear paste of relative density, and is standby;

2) Poria, Radix Curcumae, Herba Epimedii, Ramulus Cinnamomi, Radix Scutellariae add 10 times of decoctings and boil twice, wherein Radix Scutellariae until water boil rear under, each 3 hours, merge medicinal liquid, concentrated, approximately 1.1 clear paste, standby; Taking polyethylene glycol is appropriate, and heating makes melting, adds the above-mentioned thick paste of people, and mixing splashes in cooling liquid paraffin, makes drop pill, makes 1000 balls, and get final product.Wherein Polyethylene Glycol is that Macrogol 4000 and two kinds of ratios of polyethylene glycol 6000 are the mixture of 2: 1, and (Macrogol 4000: ratio polyethylene glycol 6000=2: 1) is 1: 1 for medicine and substrate.

Embodiment 3

The preparation of medicinal tablet of the present invention

Prescription:

Rhizoma Saururi (Herba Saururi) 300g Herba Hyperici Japonici 200g Chrysosplenium nudicaule Bunge 200g

Poria 120g Radix Scutellariae 150g Radix Curcumae 100g

Rhizoma Curcumae Longae 100g Herba Epimedii 150g Ramulus Cinnamomi 150g.

Preparation method:

1) get Rhizoma Saururi (Herba Saururi), Herba Hyperici Japonici, Chrysosplenium nudicaule Bunge, Rhizoma Curcumae Longae and add 12 times of amount 70% ethanol, refluxed 3 hours, recovery ethanol is concentrated into approximately 1.1 clear paste of relative density, and is standby;

2) Poria, Radix Curcumae, Herba Epimedii, Ramulus Cinnamomi, Radix Scutellariae add 10 times of decoctings and boil twice, wherein Radix Scutellariae until water boil rear under, each 3 hours, merge medicinal liquid, concentrated, approximately 1.1 clear paste, standby;

4) with step 1) clear paste and 2) clear paste mix, add proper starch; Add the moderate lubrication agent, make 1000 and get final product.

Above; be only preferred embodiment of the present invention, but protection scope of the present invention is not limited to this, anyly is familiar with those skilled in the art in the technical scope that the present invention discloses; the variation that can expect easily or replacement are within all should being encompassed in protection scope of the present invention.Therefore, protection scope of the present invention should be as the criterion with the protection domain that claim was defined.

Claims (7)

1. medicine for the treatment of hepatitis is characterized in that this medicine made by the crude drug that comprises following weight ratio:

Rhizoma Saururi (Herba Saururi) 300-600 part Herba Hyperici Japonici 200-500 part Chrysosplenium nudicaule Bunge 200-500 part

Poria 100-300 part Radix Scutellariae 100-300 part Radix Curcumae 100-300 part

Rhizoma Curcumae Longae 100-300 part Herba Epimedii 100-200 part Ramulus Cinnamomi 100-200 part

2. medicine according to claim 1, the weight ratio of its crude drug is:

Rhizoma Saururi (Herba Saururi) 400-500 part Herba Hyperici Japonici 300-400 part Chrysosplenium nudicaule Bunge 300-400 part

Poria 200-300 part Radix Scutellariae 200-300 part Radix Curcumae 200-300 part

Rhizoma Curcumae Longae 200-250 part Herba Epimedii 150-200 part Ramulus Cinnamomi 150-200 part

3. medicine according to claim 1, the weight ratio of its crude drug is:

350 parts of 350 parts of Chrysosplenium nudicaule Bunges of 450 portions of Herba Hyperici Japonici of Rhizoma Saururi (Herba Saururi)

260 parts of 260 portions of Radix Curcumaes of 260 parts of Radix Scutellariaes of Poria

180 parts of 180 parts of Ramulus Cinnamomi of 260 parts of Herba Epimedii of Rhizoma Curcumae Longae

4. medicine according to claim 2, the weight ratio of its crude drug is:

500 parts of 500 parts of Chrysosplenium nudicaule Bunges of 600 portions of Herba Hyperici Japonici of Rhizoma Saururi (Herba Saururi)

200 parts of 200 portions of Radix Curcumaes of 200 parts of Radix Scutellariaes of Poria

180 parts of 180 parts of Ramulus Cinnamomi of 200 parts of Herba Epimedii of Rhizoma Curcumae Longae

5. according to claim 1-4 arbitrary described medicines, is characterized in that this pharmaceutical dosage form is tablet, granule, hard capsule, soft capsule, pill, drop pill, slow releasing tablet or controlled release tablet.

6. the preparation method of medicine according to claim 5 is characterized in that this medicine made by the following step:

1) get Rhizoma Saururi (Herba Saururi), Herba Hyperici Japonici, Chrysosplenium nudicaule Bunge, Rhizoma Curcumae Longae and add 12 times of amount 70% ethanol, refluxed 3 hours, recovery ethanol is concentrated into approximately 1.1 clear paste of relative density, and is standby;

2) Poria, Radix Curcumae, Herba Epimedii, Ramulus Cinnamomi, Radix Scutellariae add 10 times of decoctings and boil twice, wherein Radix Scutellariae until water boil rear under, each 3 hours, merge medicinal liquid, concentrated, approximately 1.1 clear paste, standby;

4) with step 1) clear paste and 2) clear paste mix, add suitable pharmaceutically acceptable adjuvant, step is made tablet, granule, hard capsule, soft capsule, pill, drop pill, slow releasing tablet or controlled release tablet routinely.

7. according to claim 1-4 described medicines, is characterized in that being used for the treatment of acute jaundice and anicteric hepatitis, delay property, chronic hepatitis.