CN1274363C - Auxiliary therapeutic agent for C type hepatitis - Google Patents

Abstract

The present invention relates to an auxiliary therapeutic agent for hepatitis C, which is matched with a compound therapeutic method (interferon and Ribavirin) for treating hepatitis C. The present invention is composed of 50 to 90 of aweto and 10 to 50 of astragalus according to weight ratio. The auxiliary therapeutic agent can regulate the immune function of a patient with the hepatitis C and can kill viruses by matching the existing interferon therapeutic method, and thus, the curative effect on treating the hepatitis C can be improved.

Description

C type hepatitis auxiliary therapeutical agent

Technical field

The present invention relates to a kind ofly have the therapeutic agent of Cordyceps, Radix Astragali composition as auxiliary treatment C type hepatitis, its C type hepatitis combination therapy (interferon and Ribavirin) of can arranging in pairs or groups is to improve cure rate of C type hepatitis.

Background technology

Hepatitis C virus is a kind of RNA viruses, finds in 1989, is called non-a non-b hepatitis (Non-A in the past, Non-B hepatitis), cause by blood transfusion mostly, find this virus after, the reviewer before blood transfusion, whole blood screening all in advance, incidence rate declines to a great extent then.

C type hepatitis is respectively I, II, four kinds of genotype of III, IV according to the classification of okamotoShi, be mainly geno typeII in the C in Taiwan type hepatitis and account for 73%, secondly for typeIII account for 13% and typeIV account for 3%.Use interferon therapy C type hepatitis with more effective for III type and IV type, and relatively poor for II type and I type effect.The not good pact of viral Cl of independent use interferon therapy chronic hepatitis is 20-30% only, and therefore, the combination treatment that the whole world all adopts interferon to merge Ribavirin is at present treated C type hepatitis, it is said to reach the effect that doubles.The interferon of another long-acting type (as the pegylated interferon) also develops, and it is to utilize biotechnology that interferon is slowly discharged, and more traditional interferon of its half-life is long ten times and maintain in the sufferer blood, and the number of times that sufferer is gone to a doctor weekly reduces.

The therapeutic modality of present C type hepatitis, adopt interferon therapy that preferable curative effect is arranged more separately with the combination therapy (combanation therapy) that utilizes interferon to merge antiviral drugs Ribavirin, but, the treatment back finds also only to have 18% to reach the persistent virus removing, certainly, if the prolongation interferon no doubt can improve its persistent virus and be scavenged into 30% to year the course of treatment, but burden such as side effects of pharmaceutical drugs and cost, it is intolerable to be still patient institute.With side effects of pharmaceutical drugs:

The side effect of interferon

The injection initial stage: heavy cold such as fever, headache, muscular soreness, Evil heart symptom are arranged, but after one to two week, promptly can disappear.

Late period: can produce that tired, muscular soreness, leukocyte slightly descend, anemia melancholy and anxiety, lather, lose weight and symptom such as lose hair.

The side effect of antiviral drugs Ribavirin: anemia is arranged, cough, scratch where it itches, symptom such as erythema and insomnia.

Summary of the invention

The object of the present invention is to provide a kind of C type hepatitis auxiliary therapeutical agent, this auxiliary therapeutical agent collocation C type hepatitis combination therapy (interferon and Ribavirin), its effect is better than present any therapeutic modality, especially after taking this auxiliary therapeutical agent, the intravital natural killer cell of patient with liver cirrhosis, CD8+ cell, CD4+ cell and CD4+/CD8+ cells ratio obviously increase, IgG, IgA then can reduce, and complement concentration also improves relatively in the serum, and therefore the effect of carrying with patient's immune function is arranged.

The specific embodiment

For achieving the above object, C type hepatitis auxiliary therapeutical agent provided by the invention, comprises with treatment C type hepatitis in order to collocation C type hepatitis combination therapy (interferon and Ribavirin):

The Cordyceps of weight ratio 50 to 90 (Cordyceps sinensis) reaches

The Radix Astragali of weight ratio 10 to 50 (Astragalus memsrancens).

Wherein, Cordyceps refers to China pilose spore (Hirsutella sinensis) the mycelium submerged fermentation culture of its phorozoon.

Wherein, Cordyceps refer to Cordyceps institute's separation and purification and mycelium (strain), comprise:

China's Paecilomyces varioti (Paecilomyces sinensi), Chinese golden spore mould (Chrysosporiumsinense), worm give birth to mycelium submerged fermentation cultures such as bunch spore (Sporothrix insectorum), Stachybotrys atra (Stachybotrys sp.), the curved neck mould (Tolypocladium sp.) of China, the high Paecilomyces varioti of Vespertilio, Hirsutella hepiali Chen et Shen.

Wherein, the preferable weight ratio of Cordyceps is 70 to 80, and Radix Astragali is 20 to 30.

Wherein, the zinc that also comprises weight ratio 5 to 10.

Wherein, comprise: the Radix Astragali of the Cordyceps of weight ratio 75 to 80, weight ratio 10 to 20, and the zinc of weight ratio 5 to 10.

Main component in this auxiliary therapeutical agent and to the pharmacological effect of treatment C type hepatitis, division is as follows:

Cordyceps (Cordyceps sinensis)

Composition: Cordyceps contains many active substances, comprising: amino acid, Polysaccharides (polysaccharide), cordycepin (cordycepin), cordycepic acid (cordycepic acid), lysergol (ergosterol), nucleotides (nucleutide), super oxygen disproportionation ferment (SOD) and trace element (traceelements).Wherein, nucleotides makes cell active, improves function of human body and the ability of resisting the thing that causes a disease naturally.

Pharmacological effect: the pharmacological action of Cordyceps comprise antibiotic, antiinflammatory, analgesic, calm, promote vasodilation, relieving asthma, anti-arrhythmia, enhance metabolism, aging resistance, antitumor (cancer) and immune stimulating activity.Generally be used for eliminating the phlegm more, antitussive, enhancing energy, restore and impotence due to deficiency of the kidney after being ill, also effective in cure in following disease, as: pulmonary tuberculosis, anemia, angina pectoris, nephritis, hepatitis, liver cirrhosis, hypertension, diabetes and multiple treatment of cancer also have example clinically.

In the pharmacological research document, the effect that Cordyceps once was mentioned roughly has in addition: pair cell immunity or humoral immunization, the dual regulation that have inhibition, promotes.Its water extract can promote the thymocyte cell mitosis, directly stimulates the increment of T lymphocyte.With Semen Persicae and with the treatment posthepatitic cirrhosis, can increase the lymphocyte conversion ratio, natural killer cell function, CD4+/CD8+ ratio.It faces upward the effect of system humoral immunization to posthepatitic cirrhosis treatment demonstration, reduces IgG, IgA etc.

Radix Astragali (Astragalus memsrancens)

Composition: Radix Astragali is the root of Duo Nian Sheng Beans section herbaceous plant Radix Astragali, and is of a great variety, formal name used at school: Astragalus memsrancens, popular name: Milk-Vetch Root.Be a kind of southern china herbaceos perennial that is grown in, use the position to be root, the root center is a buff, tastes to have sweet taste.The Radix Astragali medicinal part is a root, is a kind of herbaceos perennial very common, as safe as a house, also is the tonic medicine that the traditional Chinese medical science is widely used for QI invigorating most.The modern science man carries out extensive studies to the pharmacological action and the chemical analysis of Radix Astragali, analyze Radix Astragali and mainly contain polysaccharide, monosaccharide, flavonoid, alkaloid (choline, betanin), several amino acids, glucuronic acid and micro-folic acid etc., reach multiple minor metallic elements such as selenium, silicon.

Pharmacological effect: according to reliable reported in literature, Radix Astragali has become the required important immunity of treatment cancer and these two kinds of diseases of AIDS and has adjusted agent, can support the immune system of having changeed weak, the medical herbs of interferon system in can body as a kind of.In addition, also to add yellow works gradually be one of main composition to health food abroad in recent years, to provide consumer with another selection as the treatment disease of natural goods medicine.With regard to the pharmacological effect of Radix Astragali, learn that through experiment it is aspect the antibody generation: the spleen antigen binding cell (the presoma cell that comprises T cell, B cell) to the immunoreation commitment has the promotion proliferative effect.Normal person or sufferer all there are cycli phosphate gland sweet (cAMP) in the spleen of enhancement, and IgG in the blood, the ability of IgA and IgM.Aspect cellular immunization, to chronic tracheitis, chronic hepatitis patient and the healthy function that the enhancing cellular immunization is arranged per capita.

Radix Astragali has extensively and significant effects immunologic function, the effect that has enhancing or regulate.Prove that in zoopery Radix Astragali can promote the virus induction gamma interferon and suppress virus breeding.

The evaluation of Cordyceps

Cordyceps of the present invention, the generalized mycelium (strain) that has comprised asexual generation institute's separation and purification of alleged in the literature Cordyceps correspondence and got, include: China pilose spore (Hirsutella sinensis), China's Paecilomyces varioti (Paecilomyces sinensi), China's golden spore mould (Chrysosporium sinense), worm gives birth to bunch spore (Sporothrix insectorum), Stachybotrys atra (Stachybotrys sp.), the curved neck mould (Tolypocladium sp.) of China, peacilomyce hepiahi, mycelial submerged fermentation culture such as Hirsutella hepiali Chen et Shen, and alleged Cordyceps is meant China pilose spore (Hirsutella sinensis) in all narration of following the present invention and operation.Though China pilose spore was reported to the phorozoon of Cordyceps in 1989, it is academic the point at issue always.Therefore, whether applicant's United States Patent (USP) power US6251606 and two Cordyceps authenticate technologies of US6271003 by having obtained already are the bioassay of Cordyceps to China pilose spore, and the result confirms that China pilose spore really is the phorozoon of Cordyceps.In addition, other research report is also pointed out, find that by the ITS sequence that compares between them the natural Cordyceps and the genetic distance of China pilose spore are very low (＜0.02) (being that likelihood is very high), and and Chinese Paecilomyces varioti (Paecilomyces sinensi), Stachybotrys atra (Stachybotrys sp.), the genetic distance of curved neck mould (Tolypocladium sp.) is big (being that likelihood is low) quite, be respectively 0.34,0.21 and 0.25.Therefore, the present invention selects to represent the object of Cordyceps as operation with China pilose spore.But this selection is not to negate other in view of the above as Chinese Paecilomyces varioti, Stachybotrys atra, the curved neck composition that does not have Cordyceps such as mould, and can't and reach the effect of expection as therapeutic agent component of the present invention.

The toxotest of Cordyceps (China is embraced by hair)

The health food that with Cordyceps is composition has been the main flow in the market, but for making Cordyceps of the present invention after the taking of long-time dosage, unlikely to human body generation harmful effect, especially foot is suffered from the C type hepatitis that immunologic function reduces, therefore, at the toxicity of Cordyceps (Cordyceps sinensis) (China pilose spore), entrust Taiwan Chinese Medicine institute (National Research Institute ofChinese Medicine), carry out the subacute toxicity test.

1, executive mode

Carry out continuous 14 days oral potion every day Cordyceps mycelium water extract of the present invention (Water fractin of Cordyceps MeOH extracts) subacute safe toxicological test.The extract dosage is to be reference index with 10 times of clinical administration dosage, two weeks of potion continuous oral every day, and observation experiment animal (rat) the following situation continuously:

(1). behavior performance (SMA).

(2). the variation of body weight, food and water intake amount.

(3). hematological check: as haemachrome, platelet, erythrocyte, leukocytic classification, and clotting time etc.

(4). blood biochemical is checked 12 inspections of a blood biochemical, as bilirubin, AST, ALT, BUN, Creatinine, glucose, total protein, albumin, K, Na, Ca.

(5). urine biochemical investigation: as settling ratio, protein, electrolyte content, pH value.

(6). organ and tissue slice: the micro-pathological anatomy check of main organs such as the heart, liver, lung, kidney, stomach, gallbladder.

Laboratory animal is taken continuously, Cordyceps mycelium water extract 15 days, after observing statistics, find, to taking relatively did not influence of feedstuff, amount of drinking water, urine amount and matched group, blood mesophytization value shows that the reference value plasma protein of nutrition of whole body standard increases, and relative BUN, protein also increases in the urine, but muroid and human difference one for containing protein in the urine and increasing with the amount of blood plasma, be not because of the caused toxicity phenomenon of medicine.

Can learn that by above result worm summer in winter lead fungi filament water extract of the present invention there is no the influence of subacute toxicity for the laboratory animal rat.

Experimental pre-Clinical

For further verifying the drug effect of auxiliary therapeutical agent of the present invention, the spy cooperates the pre-Clinical of experimentizing property with doctor, with auxiliary therapeutical agent and interferon and Ribavirin combined treatment C type hepatitis, its as a result treatment rate and can effectively improve the various side effect that C type hepatitis uses interferon and Ribavirin near 90%.

All sufferers of being tried are all accepted the deposited interferon and the Ribavirin combined treatment in 24 weeks by a definite date, cost auxiliary therapeutical agent of the present invention or placebo (placebo) again, carry out the double-blind trial (double-blind) of standard, treated for 24 weeks and followed the trail of in addition for 24 weeks again, become the experimental preceding clinical experiment that was total up to for 48 weeks.At whole experimental session, collect blood sample and data.

Began in the 2nd week the sufferer grouping and give experimental group to replenish auxiliary therapeutical agent of the present invention or placebo, merge the Ribavirin treatment in the 24th all interferon and finish, auxiliary therapeutical agent or placebo still continue to provide to finishing in the 48th week.Blood sample and data comprise:

The mutually sharp biochemical numerical value-WBC of blood drawing check, Hemoglobin, Platelet, BUN, Creatinine, SGOT/SGPT, HCV-RNA are qualitative.

Malaise symptoms kind and frequency

Experiment condition that experimental clinical experiment is carried out and result followed are as shown in following:

Experimental pre-Clinical one

1, medicine: 6 months treatment phases, subcutaneous injection Luo Shi Roferon-A (IFN) 300 ten thousand units, 3 times weekly (not having collocation antiviral agents Ribavirin), and, last till that always the mat woven of fine bamboo strips finished in 6 months in treatment phase the 2nd all oral auxiliary therapeutical agents of the present invention of beginning or placebo.

2, experimenter's number: 28 people, all do not accepted interferon therapy, organize into groups at random.

3, " IFN+ auxiliary therapeutical agent " group: 10 people, the simple interferon therapy auxiliary therapeutical agent of the present invention of arranging in pairs or groups.

4, " IPN " group: 18 people, simple interferon therapy collocation placebo.

5, continue virus sweep rate % (SVR): as table 1

Experimental pre-Clinical one result of table 1

Account for the percentage ratio of total experimenter's mouth in the bracket for it

6, conclusion:

(1). add auxiliary therapeutical agent collocation treatment of the present invention, can promote effect of interferon.

(2). add auxiliary therapeutical agent of the present invention collocation treatment, can reduce the recurrence jail after the treatment.

Experimental pre-Clinical two

1, medicine: adopt combination therapy, subcutaneous injection Luo Shi Roferon-A (IFN) 300 ten thousand units 3 times weekly add 1000 milligrams of antiviral agents Ribavirin 2 times weekly.And in treatment phase second all oral auxiliary therapeutical agents of the present invention of beginning or placebo, 6 months altogether treatment phase.

2, experimenter's number: 20 people, all do not accepted interferon therapy, organize into groups at random.

3, " IFN+ auxiliary therapeutical agent " group: 8 people, standard combination therapy collocation auxiliary therapeutical agent.

4, " IFN " group: 12 people, standard combination therapy collocation placebo.

5, continue virus sweep rate % (SVR): as table 2

Experimental pre-Clinical two results of table 2

Account for the percentage ratio of total experimenter's mouth in the bracket for it

6, conclusion:

(1) adds auxiliary therapeutical agent collocation treatment of the present invention, can promote the therapeutic effect of combination therapy (IFN+Ribavirin).

(2) add auxiliary therapeutical agent collocation treatment of the present invention, can reduce the relapse rate after the treatment; 8 are tried among the patient, and 7 states of still keeping the virus safe removing in treatment in back 2 years are arranged.

(3) in this test, add the effect that as if antiviral agents Ribavirin do not improve treatment.

Experimental pre-Clinical three

1, medicine: 6 months treatment phases, subcutaneous injection Luo Shi Roferon-A (IFN) 300 ten thousand units 3 times weekly add 1000 milligrams of antiviral agents Ribavirin 2 times weekly, and in second week of the treatment phase oral auxiliary therapeutical agent of the present invention of beginning or placebo.

2, experimenter's number: 32 people, all do not accepted interferon therapy, organize into groups at random.

3, " IFN+ auxiliary therapeutical agent " group: 16 people, the standard combination therapy auxiliary therapeutical agent of the present invention of arranging in pairs or groups.

4, " IFN " group: 16 people, standard combination therapy collocation placebo.

5. continue virus sweep rate % (SVR): as table 3

Experimental pre-Clinical three results of table 3

Account for the percentage ratio of total experimenter's mouth in the bracket for it

Side effect relatively when 6, treating

Side effect	" IFN+ auxiliary therapeutical agent " group number	" IFN " group number
			The melancholy irritability insomnia of the slight alopecia erythema of fever, headache, the unusual eye movement of the tired arthralgia of the DOMS anaemia 10g/dl＜ferroheme＜11g/dl 9g/dl＜ferroheme＜10g/dl ferroheme＜9g/dl that loses weight	13(83％) 12(75％) 13(83％) 10(63％) 9(56％) 11(69％) 10(63％) 2(13％) 12(75％) 9(56％) 5(31％) 1(6％) 1(6％)	14(90％) 12(75％) 12(75％) 13(83％) 10(63％) 11(69％) 11(69％) 3(19％) 13(83％) 14(90％) 9(56％) 2(13％) 0(0％)

Leukopenia 3,000/UL＜leukocyte＜3,500/UL 2,500/UL＜leukocyte＜3,000/UL leukocyte＜2,500/UL

3(19％) 0(0％) 3(19％)

5(31％) 0(0％) 1(6％)

Represent it to account for the percentage ratio of total experimenter's mouth in the bracket

7, conclusion:

(1) adds auxiliary therapeutical agent collocation combination therapy of the present invention (IFN+Ribavirin) treatment, represented the effect that viral clearance rate promotes, also reduced relapse rate simultaneously.

(2) in the side effect in when treatment, that group that adds auxiliary therapeutical agent of the present invention is arranged, unusual ocular movement, lose weight, side effect such as haemachrome and leukocyte cell minimizing, the situation of slowing down is all arranged.

By above-mentioned various experimental results and data as can be known, the C type treating hepatitis mode that auxiliary therapeutical agent of the present invention can be arranged in pairs or groups present really, and can effectively increase its curative effect, and alleviate the side effect of sufferer when treatment.

Mainly formed as above-mentioned C type hepatitis auxiliary therapeutical agent of the present invention, yet in the implementation process of reality, still can be added other micro-elements to increase its therapeutic effect to C type treating hepatitis by Cordyceps, Radix Astragali.For example, zinc (Zinc) element that in C type hepatitis auxiliary therapeutical agent of the present invention, adds trace, can replenish the zinc that is run off in the C type hepatitis body, and zinc element just has direct relation for human immunocyte's's (T cell) generation from the beginning, therefore, zinc is incorporated in the C type hepatitis auxiliary therapeutical agent of the present invention immunocyte that can the hypertrophy patient and reach the effect that promotes immunologic function.The about 5-10 of weight ratio of the trace zinc element of this adding.Above-mentioned zinc element replenishes, also can be in other way, and non-being unique embodiment in the direct adding C type of the present invention hepatitis auxiliary therapeutical agent.

Claims (5)

1, a kind of C type hepatitis auxiliary therapeutical agent comprises: the Radix Astragali of the Cordyceps China pilose spore of weight ratio 50 to 90 and weight ratio 10 to 50; This C type hepatitis auxiliary therapeutical agent in order to collocation C type hepatitis combination therapy interferon and Ribavirin with treatment C type hepatitis.

2, C type hepatitis auxiliary therapeutical agent as claimed in claim 1 is characterized in that, Cordyceps refers to the Hirsutella sinensis mycelium submerged fermentation culture of its phorozoon.

3, C type hepatitis auxiliary therapeutical agent as claimed in claim 1 is characterized in that the weight ratio of Cordyceps is 70 to 80, and Radix Astragali is 20 to 30.

4, C type hepatitis auxiliary therapeutical agent as claimed in claim 1 is characterized in that, also comprises the zinc of weight ratio 5 to 10.

5, C type hepatitis auxiliary therapeutical agent as claimed in claim 4 is characterized in that, comprises: the Radix Astragali of the Cordyceps China pilose spore of weight ratio 75 to 80, weight ratio 10 to 20, and the zinc of weight ratio 5 to 10.