CN103585291A - Application of herba delphinii extract in preparation of drugs treating AIDS - Google Patents
Application of herba delphinii extract in preparation of drugs treating AIDS Download PDFInfo
- Publication number
- CN103585291A CN103585291A CN201310525344.XA CN201310525344A CN103585291A CN 103585291 A CN103585291 A CN 103585291A CN 201310525344 A CN201310525344 A CN 201310525344A CN 103585291 A CN103585291 A CN 103585291A
- Authority
- CN
- China
- Prior art keywords
- extract
- herba delphinii
- delphinii grandiflori
- hair herba
- exhibition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Landscapes
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Abstract
The invention relates to new application of a herba delphinii extract in preparation of drugs treating AIDS. The herba delphinii extract is prepared by: extracting herba delphinii, and conducting macroporous adsorption resin purification twice. The herba delphinii extract provided by the invention is of great significance in preparing drugs treating AIDS.
Description
Technical field
The invention belongs to biomedicine field, relate to the application of a kind of Chinese crude drug extract in preparation treatment AIDS-treating medicine, specifically relate to a kind of application of mao Herba delphinii grandiflori extract in preparation treatment AIDS-treating medicine of opening up.
Background technology
Acquired immune deficiency syndrome (AIDS) is the new virus sexually transmitted disease of finding in 1981, and the traditional Chinese medical science past is not on the books to it.The traditional Chinese medical science is dialectical to acquired immune deficiency syndrome (AIDS), thinks that acquired immune deficiency syndrome (AIDS) belongs to epidemic disease category.The cause of disease is the scorchingly hot evil invasion and attack of epidemic disease, deficiency of vital QI and causing.Pathogenesis is mainly weakened defensive QI, yang-energy damage, and internal organs are got involved, and cause that the deficiency of the lung is insufficiency of the spleen to suffer from a deficiency of the kidney secondary infection.Thermal burn venation, coagulation of QI-blood, Xing Cheng mass in the abdomen lump tumor.
Syndrome Differentiation of Chinese Medicine " card ": mainly distinguish ebb and flow between pathogen and vital QI and deficiency syndrome excess syndrome.HIV (human immunodeficiency virus) is evil poison, in evil poison enters and the change of disease, with the dynamic change that the heresy of body healthy energy is just being resisted, is advancing of disease process.Infect and take in early days the domination of pathogen as main, mid-term " because of the real void that causes ", late period " excess caused by deficiency ".The acquired immune deficiency syndrome (AIDS) state of an illness copies changeable, and acquired immune deficiency syndrome (AIDS) and secondary infection thereof all can form " disease ", and has difference " type " and " phase ".The traditional Chinese medical science has dialectical differential diagnosis of diseases to acquired immune deficiency syndrome (AIDS), and typing the different diagnosis and treatment projects such as by stages.
The Chinese medicine of acquired immune deficiency syndrome (AIDS) still belongs to conceptual phase at present, at home and abroad there is no at present and generally acknowledges curative effect certainly go through AIDS virus resisting Chinese medicine or the Chinese medicine monomer compound produced.AIDS virus resisting plant amedica and Chinese medicine research mainly divide 3 kinds of approach, AIDS virus resisting Chinese medicinal plant medicine and composition thereof that smoking set obtains, and some is in clinic trial.
Since HIV (human immunodeficiency virus) is found, use in the world HIV (human immunodeficiency virus) cell culture and reverse transcriptase, the experiment in vitro such as protease and intergrase method, in the time of extensive SCREENED COMPOUND, also screen in a large number plant and Chinese herbal medicine extract and composition thereof, also studied some compound Chinese medicinal preparation, found the active drug of inhibiting HIV in vitro, the viremia of the suppressed simian immunodeficiency virus having (SIV) infected monkey.Some is in clinic trial, not yet clear and definite effect.
China removes Africa treatment AIDS patients from 1987 Nian Pai combination of Chinese and Western medicine medical teams.Domestic before 2002, lack specially good effect Anti-AIDS Drugs, Chinese and western medicine, combines with dialectical to AIDS patients differential diagnosis of diseases according to theory of Chinese medical science clinical, with heat-clearing and toxic substances removing, strengthening the body resistance, or removing heat from blood the kidney invigorating, the rule for the treatment of such as blood circulation promoting and blood stasis dispelling, by the property of Chinese materia medica, select Chinese medicine, prescribed treatment.By clinical practice, think that some Medical Complex Prescription in Treating AIDS can improve symptom, mitigate the disease.The AIDS patients of in recent years laboratory diagnosis being made a definite diagnosis, adopts treatment by Chinese herbs, establishes matched group, during treating, regularly detects blood disease carrying capacity (HIV-RNA) and cd4 cell level, evaluation effect.There is report can improve symptom, improve immunity, mostly still in clinical verification.Enter clinical anti-HIV single medicinal material or plant amedica and Chinese medicine compound as follows:
Glycyrrhizin: glycyrrhizin (glycyrrhizin, GL) be the glycyrrhizin that glycyrrhiza uralensis fisch (Glycyrrhiza glabra L) extracts, there is broad-spectrum disease resistance toxic action, vitro inhibition HIV1-RT, in cell culture, suppress HIV cell fusion, also resisiting influenza virus and SARS virus, experimental results show that in body and can protect pneumonia death and the pneumonopathy that influenza infection mice causes to become; The CCl of protection mice
4toxic liver injury; Induce gamma interferon; There is parahormone effect.Conventional its intravenous drip treatment chronic hepatitis B of Japan, also once tried out treatment AIDS patients, can suppress serum HIV-1-P24 antigen, rising cd4 cell.Lv Weibai professor 1988-1992 can treat AIDS patients African Tanzania application glycyrrhizin oral formulations gram Chinese mugwort can improve symptom, and cd4 cell slightly rises.Its effect is not yet verified.
Trichosanthin: trichosanthin (Trichosanthin, TCS, GLQ223, Q material) be that Chinese medicine Fructus Trichosanthis (Trichosanthes kirilowii) belongs to Cucurbitaceae (Cucurbitaceae), China's main Chinese medicine ingredients for the Chinese medicine compound of miscarrying among the people is Fructus Trichosanthis, the effective ingredient of China scientist isolation identification device antiearly pregnancy and induced labor is trichosanthin, molecular weight is 27kD, one, secondary structure and three dimensional structure are understood fully completely, for the synthetic toxalbumin of Profilin, ribosome inactivating protein (the Ribosome Inactivating Protein of strand, RIP).The U.S. is when screening anti-HIV-1 medicines, find that it suppresses HIV-1 cell fusion in lymphocyte is cultivated, thereafter the P24 antigen and the RNA that find HIV-1 in mononuclear phagocyte is cultivated, can suppress blood plasma HIV-1 in the intravenous injection of 3 simian acquired immunodeficiency syndrome viruses (SIV) infected monkey.The U.S. is used intravenous drip treatment AIDS patients in forest farm, can suppress T lymphocyte and the interior HIV-1-P24 antigen of mononuclear phagocyte that peripheral blood HIV-1 infects, and CD4/ CD8 ratio is slightly raise.Owing to can causing that anaphylactic reaction is dead, neurovirulent Mental Subnormality and nephrotoxicity reaction, clinical experiment is ended.From Radix Trichosanthis, isolate in recent years other albumen TAP29, molecular weight, at 29 kD, also have the effect that suppresses HIV-1, but toxicity is less, not in clinic trial.In addition the Radix Phytolaccae albumen (Pokeweed protein) of the bitter melon protein of Fructus Momordicae charantiae (MOmordica charantia) and Radix Phytolaccae (Phytolacca americana) etc. has the effect that suppresses HIV.
Hypericin: plant Herba Hyperici Monogyni (St. John Wort, Hypericum perforatum) its extract for treating depression for folk tradition, the active component proposing from flower is hypericin (hypericin), it is the multi-ring dimerization anthraquinone analog compound of aromatic series, for anti-depression drug, complete synthesis.Hypericin has multiple antiviral activity, suppresses HIV in cell culture, and what its mechanism of action was blocking virus undresses, assembling and release, and the effect of killing the virus, can pass through blood brain barrier.In cell culture, can suppress murine leukemia virus breeding.Can suppress the splenomegaly that murine leukemia virus infecting mouse causes in vivo, also can suppress duck hepatitis B virus infection Sanguis Anas domestica and ask viral DNA, and have wide spectrum antibacterial activity.Once in clinical I/II phase treatment on probation HIV sufferers, because there being light sensitization to stop test.
Dextrorotation lane element A: be dextrorotation lane element A(+Calanolide A) native compound of report separation from Malaysian rainforest plant Calophyllum lanigerum in 1992, Mus coumarin kind compound, suppress HIV1-RT, but invalid to HIV-2.Belong to non-nucleoside HIV1-RT inhibitor, in cell culture, multi-to-multi lives that the AZT of clinical separation is responsive and drug resistance HIV-1 is effective, and and AZT, NVP has synergism.In experimental model in HIV hollow fiber pipe Mice Body (HIV hollow fiber mouse model), proof has AIDS virus resisting effect, can strengthen drug effect with AZT use in conjunction.Complete synthesis, having carried out its clinical trial proof of I-II has the therapeutic effect that suppresses HIV-1 infection, and toxicity is little, and side effect is light, has headache and inappetence etc., effective with AZT drug combination.Be the single plant component of the unique II of entering phase clinical experiment at present, observing in checking curative effect, not yet approval is produced.
Herba Sidae Rhombifoliae soup: Herba Sidae Rhombifoliae soup (Radix Bupleuri, Radix Ginseng, the Rhizoma Pinelliae, Radix Scutellariae, Radix Glycyrrhizae, Rhizoma Zingiberis Recens, Fructus Jujubae)
It is Zhang Zhongjing Treatise on Febrile Diseases side.Hepatitis B is treated with it by Japan, finds that it suppresses HIV in cell culture.The U.S., at the clinical numerical example AIDS patients that is used for the treatment of, can reduce blood-serum P 24 antigens.We prove that it has the effect that suppresses HIV1-RT and suppress HIV-1 in cell culture.Study respectively the effect of its 7 kinds of composition Chinese medicines, only find that Radix Scutellariae water extract and composition baicalin (baicalin) thereof have the HIV-1 of inhibition effect, in cell free system, suppress HIV1-RT in vitro, in human T-cell and peripheral blood lymphocytes cultivation, suppress HIV-1 cytopathy, FLuorescent antigen and P24 antigen, murine leukemia virus infecting mouse is oral in body suppresses splenomegaly and blood leukocytes raises.Japan's Ono report noroxylin (baicalien) suppresses HIV1-RT.
In grind No. I: in to grind No. I commodity such as (principal agent has Herba Violae, Radix Trichosanthis composition) by name: Chinese mugwort
Gram electuary, take heat-clearing and toxic substances removing as the prescription 1992-1993 of rule for the treatment of ，You China Chinese medicine research institute in African Tanzania to the clinical practice of early metaphase acquired immune deficiency syndrome (AIDS), think and have certain symptom of improving, improve the effect of immunity.Laboratory proves that this medicine vitro inhibition hiv reverse transcriptase is active, in body, simian acquired immunodeficiency syndrome poison infected monkey experimental therapy result is shown, can reduce plasma viral titre, and can improve cd4 cell number and CD4/CD8 ratio and T, bone-marrow-derived lymphocyte numerical value, inducement interferon and generation immunoloregulation function.Once in Africa and China's clinic trial, not yet ratified clinical verification.
Zhongyan No. 2: Zhongyan No. 2 (Radix Astragali, Radix Ginseng, Radix Angelicae Sinensis, Fructus Lycii and Radix Glycyrrhizae etc.) is China's traditional Chinese medical science
Academy medical team prescription.1992 at African Tanzania treatment AIDS patients.1998-1999 is at African special outpatient clinic to 29 routine AIDS patients treatments, and 2/16 routine HIV virus load declines, and the routine CD4 of CD4 8/29 raises.2001-2002 helps the routine AIDS patients of peace hospitalize 15 in Beijing, 3/15 routine virus load declines, and the routine CD4 of CD4 1/15 raises.Be improved the effect of symptom.Experimental results show that this medicine shows simian acquired immunodeficiency syndrome poison infected monkey experimental therapy in human body, medication 4-12 week can be reduced plasma viral titre, P27 antigen, and can improve cd4 cell number, infected monkey lymphocyte is had to activation.
Exhibition hair Herba delphinii grandiflori is for for ranunculaceae plant exhibition mao Herba delphinii grandiflori Delphinium kamaonense Huth var.glabrescens (W.T.Wang) W.T.Wang and belong to the dry aerial parts of several plants together.Gather 6～August, dries.Record in < < Drug Standard of Ministry of Public Health of the Peoples Republic of China Tibetan medicine (first) > >, standard number: WS3-BC-0088-95.Cool in nature, bitter in the mouth.There is heat clearing away, antidiarrheal dysentery, the more effect of skin ulcer.For intestinal heat diarrhoea, dysentery; The external application open sore part.For China, hide the common drug of the minority areas such as illiteracy.But the basic research of relevant exhibition hair Herba delphinii grandiflori is still very limited, and the follow-up promotion and application of this medical material are restricted.Modern study shows, opens up a hair Herba delphinii grandiflori and contains alkaloids composition; Exhibition hair Herba delphinii grandiflori pharmacological research has no report.
Domestic patent search result, has no exhibition hair Herba delphinii grandiflori Patents.
Above-mentioned document and patent etc., there is not yet exhibition hair Herba delphinii grandiflori or exhibition hair Herba delphinii grandiflori extract for the preparation of the report for the treatment of AIDS-treating medicine.
Summary of the invention
The object of the present invention is to provide a kind of application of mao Herba delphinii grandiflori extract in preparation treatment AIDS-treating medicine of opening up.
The present invention is achieved through the following technical solutions:
The present invention's exhibition hair used Herba delphinii grandiflori is ranunculaceae plant exhibition hair Herba delphinii grandiflori Delphinium kamaonense Huth var.glabrescens (W.T.Wang) W.T.Wang and the dry aerial parts that belong to several plants together.
A kind of mao Herba delphinii grandiflori extract of opening up of the present invention is treated the application in AIDS-treating medicine in preparation, and the preparation method of described exhibition hair Herba delphinii grandiflori extract is:
(1) exhibition hair Herba delphinii grandiflori, with concentration 50%-95% ethanol, as solvent, at 30 ℃ of-60 ℃ of warm macerating, extract, extraction time is 2-6 time, each extraction time is 2-8 hour, the 10-30 that each solvent load is exhibition hair Herba delphinii grandiflori weight doubly, filters, and obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.05-1.12, filter, obtain medicinal liquid A;
(2) medicinal liquid A step (1) being obtained, by nonpolar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 60%-95%, collects different concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained to medicinal residues A water is solvent, reflux, extract,, and extraction time is 2-5 time, each extraction time is 1-6 hour, and the 6-20 that each solvent load is exhibition hair Herba delphinii grandiflori weight doubly, filters, extracting solution is concentrated into relative density d=1.05-1.12, filters, and obtains medical liquid B;
(4) medical liquid B step (3) being obtained, by polar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 30%-80%, collects different concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract B;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B, wherein one or both mix by a certain percentage, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
The preparation method of exhibition hair Herba delphinii grandiflori extract is:
(1) exhibition hair Herba delphinii grandiflori, with concentration 50%-95% ethanol, as solvent, at 30 ℃ of-60 ℃ of warm macerating, extract, extraction time is 2-6 time, each extraction time is 2-8 hour, the 10-30 that each solvent load is exhibition hair Herba delphinii grandiflori weight doubly, filters, and obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.05-1.12, filter, obtain medicinal liquid A;
(2) medicinal liquid A step (1) being obtained, by nonpolar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 60%-95%, collects different concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained to medicinal residues A water is solvent, reflux, extract,, and extraction time is 2-5 time, each extraction time is 1-6 hour, and the 6-20 that each solvent load is exhibition hair Herba delphinii grandiflori weight doubly, filters, extracting solution is concentrated into relative density d=1.05-1.12, filters, and obtains medical liquid B;
(4) medical liquid B step (3) being obtained, by polar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 30%-80%, collects different concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract B;
(5) above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B are mixed, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
Preferred the present invention opens up a mao preparation method for Herba delphinii grandiflori extract and is:
(1) exhibition hair Herba delphinii grandiflori, with concentration 70% ethanol, as solvent, at 50 ℃ of warm macerating, extract, extraction time is 3 times, each extraction time is 4 hours, each solvent load, for 20 times of exhibition hair Herba delphinii grandiflori weight, filters, and obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.10, filter, obtain medicinal liquid A;
(2) medicinal liquid A step (1) being obtained, by D101 macroporous adsorbent resin, first washes with water, then the alcoholic solution of using concentration 60% eluting successively, collects 60% concentration ethanol eluent, and concentrate drying, must open up a hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained to medicinal residues A water is solvent, reflux, extract,, and extraction time is 3 times, and each extraction time is 2 hours, and each solvent load, for 10 times of exhibition hair Herba delphinii grandiflori weight, filters, and extracting solution is concentrated into relative density d=1.11, filters, and obtains medical liquid B;
(4) medical liquid B step (3) being obtained, by DM130 macroporous adsorbent resin, first washes with water, then uses the alcoholic solution eluting of concentration 70%, collects 70% concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract B;
(5) above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B are mixed, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
The preparation method that exhibition hair Herba delphinii grandiflori of the present invention extracts, is characterized in that: the nonpolar macroporous adsorption resin adopting is AB-8 macroporous adsorbent resin, D101 macroporous adsorbent resin; The polar macroporous adsorption resin adopting is DM130 macroporous adsorbent resin, ADS-3 macroporous adsorbent resin.
The application of exhibition hair Herba delphinii grandiflori extract of the present invention in preparation treatment AIDS-treating medicine.
Exhibition hair Herba delphinii grandiflori extract A of the present invention, the application of exhibition hair Herba delphinii grandiflori extract B in preparation treatment AIDS-treating medicine.
The treatment AIDS-treating medicine that exhibition hair Herba delphinii grandiflori extract of the present invention and chemical drugs or Chinese medicine or natural drug form.
The treatment AIDS-treating medicine that exhibition hair Herba delphinii grandiflori extract A of the present invention, exhibition hair Herba delphinii grandiflori extract B and chemical drugs or Chinese medicine or natural drug form.
Exhibition of the present invention hair Herba delphinii grandiflori extract, by the various adjuvants that add pharmaceutics to allow, makes the peroral dosage forms such as tablet on pharmaceutics, granule, capsule.
It is that raw material extracts preparation treatment acquired immune deficiency syndrome (AIDS) extract that a dry seed of leguminous plant exhibition hair Herba delphinii grandiflori Mucuna birdwoodiana Tutcher is take in the present invention's exploratory development first.This experimentation shows, the external infected by influenza of exhibition hair each extract of Herba delphinii grandiflori, parainfluenza virus I type (HVJ), respiratory syncytial virus (RSV), Coxsackie virus B 4 type (C
oxb
4), adenovirus type III ((Ard
3) and rhinoviral cytopathy compared with virus control group, all alleviate to some extent.In body, mice influenzal pneumonia is had to obvious inhibitory action, influenza to dead mouse is had to significant protective effect, show that each extract of exhibition hair Herba delphinii grandiflori has good antivirus action.Clinical observation result of the test shows, takes 12 routine HIV sufferers of exhibition hair Herba delphinii grandiflori extract for treating, obviously improves symptom, repairs hepatic and renal function, improves, stablizes or prolong CD
4decline, inhibition virus replication etc. has obvious curative effect.
The specific embodiment
Below by specific experiment example and embodiment, to a kind of, open up the application that mao Herba delphinii grandiflori extract treats in AIDS-treating medicine in preparation and be described further, but be not limited to the present invention.
Embodiment 1: the preparation of exhibition hair Herba delphinii grandiflori extract
(1) exhibition hair Herba delphinii grandiflori 20kg, with concentration 70% ethanol, as solvent, at 50 ℃ of warm macerating, extract, extraction time is 3 times, each extraction time is 4 hours, each solvent load, for 20 times of exhibition hair Herba delphinii grandiflori weight, filters, and obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.10, filter, obtain medicinal liquid A;
(2) medicinal liquid A step (1) being obtained, by D101 macroporous adsorbent resin, first washes with water, then uses the alcoholic solution eluting of concentration 60%, collects 60% concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained to medicinal residues A water is solvent, reflux, extract,, and extraction time is 3 times, and each extraction time is 2 hours, and each solvent load, for 10 times of exhibition hair Herba delphinii grandiflori weight, filters, and extracting solution is concentrated into relative density d=1.11, filters, and obtains medical liquid B;
(4) medical liquid B step (3) being obtained, by ADS-3 macroporous adsorbent resin, first washes with water, then uses the alcoholic solution eluting of concentration 70%, collects 70% concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract B;
(5) above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B are mixed, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
Embodiment 2: the preparation of exhibition hair Herba delphinii grandiflori extract
(1) exhibition hair Herba delphinii grandiflori 25kg, with concentration 50% ethanol, as solvent, at 60 ℃ of warm macerating, extract, extraction time is 6 times, each extraction time is 2 hours, each solvent load, for 10 times of exhibition hair Herba delphinii grandiflori weight, filters, and obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.12, filter, obtain medicinal liquid A;
(2) medicinal liquid A step (1) being obtained, by AB-8 nonpolar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 60%, collects 60% concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained to medicinal residues A water is solvent, reflux, extract,, and extraction time is 2 times, and each extraction time is 6 hours, and each solvent load, for 20 times of exhibition hair Herba delphinii grandiflori weight, filters, and extracting solution is concentrated into relative density d=1.05, filters, and obtains medical liquid B;
(4) medical liquid B step (3) being obtained, by ADS-3 polar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 30%, collects 30% concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract B;
(5) above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B are mixed, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
Embodiment 3: the preparation of exhibition hair Herba delphinii grandiflori extract
(1) exhibition hair Herba delphinii grandiflori, with concentration 95% ethanol, as solvent, at 30 ℃ of warm macerating, extract, extraction time is 2 times, each extraction time is 8 hours, each solvent load, for 30 times of exhibition hair Herba delphinii grandiflori weight, filters, and obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.05, filter, obtain medicinal liquid A;
(2) medicinal liquid A step (1) being obtained, by D101 nonpolar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 95%, collects 95% concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained to medicinal residues A water is solvent, reflux, extract,, and extraction time is 5 times, and each extraction time is 1 hour, and each solvent load, for 6 times of exhibition hair Herba delphinii grandiflori weight, filters, and extracting solution is concentrated into relative density d=1.12, filters, and obtains medical liquid B;
(4) medical liquid B step (3) being obtained, by ADS-3 polar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 80%, collects 80% concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract B;
(5) above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B are mixed, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
Embodiment 4: the preparation of exhibition hair Herba delphinii grandiflori extract sheet
Get embodiment 1 exhibition hair Herba delphinii grandiflori extract 270g, add starch 70g, mix, granulate, dry, sieve, add microcrystalline Cellulose 25g, magnesium stearate 3g, mixes, and is pressed into 1000, must open up hair Herba delphinii grandiflori extract sheet.
Embodiment 5: the preparation of exhibition hair Herba delphinii grandiflori extract particles
Get embodiment 2 exhibition hair Herba delphinii grandiflori extract 150g, add dextrin 95g, mix, granulate, dry, granulate, must open up hair Herba delphinii grandiflori extract particles.
Embodiment 6: the preparation of exhibition hair Herba delphinii grandiflori extract capsule
Get embodiment 3 exhibition hair Herba delphinii grandiflori extract 240g, add starch 85g, mix, granulate, dry, granulate,, must open up hair Herba delphinii grandiflori extract capsule by encapsulated 1000.
Experimental example l: the antivirus action of each extract of exhibition hair Herba delphinii grandiflori
Test material: an exhibition hair Herba delphinii grandiflori extract, an exhibition hair Herba delphinii grandiflori extract A, (prepare by the embodiment of the present invention 1 method, lot number is respectively an exhibition hair Herba delphinii grandiflori extract B: 20110708,20110709,20110710); Virazole (ribavirin) is produced by Hubei Province's institute of Pharmaceutical Industry, lot number: 20110503; SHUANGHUANGLIAN JIAONANG is produced by Jinghai Pharmaceutical Co., Ltd., Beijing, lot number: 20110701; The sick 4 type (C of influenza virus A 3 Xing, coxsackie B families
oxb
4), parainfluenza virus I type (HVJ), respiratory syncytial virus (RSV), adenovirus type III (Ard
3), rhinovirus 14 types and influenza virus A-prime Mus lung adapted strain FM1, respectively purchased from Virology Inst., Chinese Academy of Preventive Medical Science and institute of pediatrics; People's laryngeal carcinoma passage cell HEP-2 strain, purchased from Ministry of Public Health pharmaceutical biological product calibrating institute; Containing 10% calf serum, 0.29mg paddy ammonia phthalein amine/m1,100 μ l are blue or green, the Eagle'MEM of Streptomycin; Cell maintenance medium, except contained calf serum is 2%, other content are same culture fluid all.Kunming mouse ，You Shandong Province Experimental Animal Center provides.
Experimental technique
1. antiviral effect in vitro: the toxicity test to Hep-2 cultured cell: medicinal liquid is cultivated and made 1:20-1:1280 doubling dilution with Eagle's, be added in the HEP-2 Tissue Culture Plate that grows up to monolayer, 100 μ l/ holes, each dilution factor medicinal liquid is done 3 multiple holes, establishes normal cell contrast simultaneously.Culture plate is put to 37 ℃, 5% C0
2in incubator, cultivate 4 days, observation of cell growing state under every day inverted microscope, that determines that obvious regression does not appear in cell minimumly releases rare multiple, postpones and accomplish minimum effective drug concentration (maximum dilution multiple) during experiment.By Reed-Muench method, calculate 50% toxic concentration (TC
50) and maximal non-toxic concentration (TC
0), the results are shown in Table 1.
The TC of table 1 pair cultured cell
0tC
50(mg/ml).
2. interior resisting virus effect: the inhibitory action to mice viral pneumonia: get 70 of mices, by body weight, be divided at random 7 groups, be respectively intact animal's matched group, viral infection matched group, trial drug 3 groups of (exhibition hair Herba delphinii grandiflori extract, exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B), virazole groups, SHUANGHUANGLIAN JIAONANG group.Except Normal group, mice is slightly anaesthetized with ether, with 15 LD50 influenza virus drop noses, infect every 0.05ml.From infecting, start gastric infusion the previous day, every day 3 times, each 0.5ml, continuous 5 days, matched group is distilled water gavage under equal conditions.After within the 6th day, taking Mouse Weight, dissect, perusal pulmonary lesion, records the degree of pulmonary's liver sample consolidation, wins full lung and weighs, and calculates one by one lung exponential quantity, and obtains lung index.Result: the mice pneumonia that each extract infected by influenza of exhibition hair Herba delphinii grandiflori causes all has obvious inhibitory action, the results are shown in Table 2.
The inhibitory action of table 2 pair mice viral pneumonia
Note: with Normal group comparison:
##p<0.01; With the comparison of virus control group: * * P<0.01, * P<0.05.
3. the protective effect of infected by influenza induced mice death: get 120 of mices, be divided at random 6 groups by body weight.Be respectively three dosage groups of trial drug, virazole group, SHUANGHUANLIAN group and viral infection matched group.Each organizes mice with after the slight anesthesia of ether, infects every 0.05ml with 2 LD50 influenza virus drop noses.From infecting, start gastric infusion the previous day, every day 3 times, each 0.5ml, continuous 7 days.After accumulative total infects, the death toll of mice, calculates mortality rate, protective rate and increase in life span, the results are shown in Table 3,4.
Table 3 infected by influenza causes the protective effect of dead mouse
Note: with infect matched group comparison:
*p<0.0l,
*p<0.05.
Table 4 infected by influenza causes the protective effect of dead mouse
Note: with infect matched group comparison:
*p<0.0l,
*p<0.05.
Table 3; table 4 result shows: in latter 14 days of mouse infection virus; the death toll of each extract group mice of exhibition hair Herba delphinii grandiflori infects matched group and obviously reduces; the mice natural law of on average surviving infects matched group and obviously extends, and shows that trial drug infected by influenza when this dosage infects to cause dead mouse and have certain protective role.
In experimentation, find the external infected by influenza of exhibition hair each extract of Herba delphinii grandiflori, parainfluenza virus I type (HVJ), respiratory syncytial virus (RSV), Coxsackie virus B 4 type (C
oxb
4), adenovirus type III ((Ard
3) and rhinoviral cytopathy compared with virus control group, all alleviate to some extent.In body, mice influenzal pneumonia is had to obvious inhibitory action, influenza to dead mouse is had to significant protective effect, show that each extract of exhibition hair Herba delphinii grandiflori has good antivirus action, therefore there is the basis developing preferably.
Experimental example 2: the clinical observation on the therapeutic effect of exhibition hair Herba delphinii grandiflori extract for treating acquired immune deficiency syndrome (AIDS)
Physical data: 12 routine cases are all HIV sufferers through hospital diagnosis, accept voluntarily clinical research; Can adhere to accepting assessment detects and treats; Age 21-63 year; Man's 8 examples, female's 3 examples; 32 years old mean age.All case never received antiviral treatments.
Diagnostic criteria: all cases all meet HIV/AIDS diagnostic criteria.
Therapeutic Method: all cases all oral the present invention are opened up a mao Herba delphinii grandiflori extract, a 1g, 3 times on the one 30 days is a course for the treatment of.
Clinical efficacy evaluation criteria: the < < Treating AIDS with Traditional Chinese Medicine pilot project clinical technology scheme > > formulating according to State Administration of Traditional Chinese Medicine, the standard of curative effect evaluation is as follows: effectively: clinical symptoms sign is improved obviously, and total mark declines>=1/3; CD
4>=30% or 50 μ l raise; Virus load reduces >0.5log/ml; Stable: clinical symptoms sign makes moderate progress, total mark decline <1/3; CD
4raise or decline <30% or 50 μ l; Virus load rises or decline <0.5log/ml.Invalid: clinical symptoms sign is without improving or increasing the weight of, and total mark does not decline or increases; CD
4>=30% or 50 μ l decline; Virus load level continues to rise, copy number rising >0.5log/ml.
Result is tired out in clinical sight: before and after treatment, symptom and sign changes: effective 8 examples are stable: and 4 examples are invalid: 0 example.
CD before and after treatment
4cellular change: effective 7 examples are stable: 4 examples are invalid: 1 example.
Before and after treatment, virus load changes: effective 7 examples are stable: and 4 examples are invalid: 1 example.
Clinical observation result shows: take 12 routine HIV sufferers of exhibition hair Herba delphinii grandiflori extract for treating, obviously improve symptom, repair hepatic and renal function, improve, stablize or prolong CD
4decline, inhibition virus replication etc. has obvious curative effect.
Claims (8)
1. open up the application of mao Herba delphinii grandiflori extract in preparation treatment AIDS-treating medicine, the preparation method of described exhibition hair Herba delphinii grandiflori extract is:
(1) exhibition hair Herba delphinii grandiflori, with concentration 50%-95% ethanol, as solvent, at 30 ℃ of-60 ℃ of warm macerating, extract, extraction time is 2-6 time, each extraction time is 2-8 hour, the 10-30 that each solvent load is exhibition hair Herba delphinii grandiflori weight doubly, filters, and obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.05-1.12, filter, obtain medicinal liquid A;
(2) medicinal liquid A step (1) being obtained, by nonpolar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 60%-95%, collects different concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained to medicinal residues A water is solvent, reflux, extract,, and extraction time is 2-5 time, each extraction time is 1-6 hour, and the 6-20 that each solvent load is exhibition hair Herba delphinii grandiflori weight doubly, filters, extracting solution is concentrated into relative density d=1.05-1.12, filters, and obtains medical liquid B;
(4) medical liquid B step (3) being obtained, by polar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 30%-80%, collects different concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract B;
(5) by above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B, wherein one or both mix by a certain percentage, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
2. the preparation method of exhibition hair Herba delphinii grandiflori extract is according to claim 1:
(1) exhibition hair Herba delphinii grandiflori, with concentration 50%-95% ethanol, as solvent, at 30 ℃ of-60 ℃ of warm macerating, extract, extraction time is 2-6 time, each extraction time is 2-8 hour, the 10-30 that each solvent load is exhibition hair Herba delphinii grandiflori weight doubly, filters, and obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.05-1.12, filter, obtain medicinal liquid A;
(2) medicinal liquid A step (1) being obtained, by nonpolar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 60%-95%, collects different concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained to medicinal residues A water is solvent, reflux, extract,, and extraction time is 2-5 time, each extraction time is 1-6 hour, and the 6-20 that each solvent load is exhibition hair Herba delphinii grandiflori weight doubly, filters, extracting solution is concentrated into relative density d=1.05-1.12, filters, and obtains medical liquid B;
(4) medical liquid B step (3) being obtained, by polar macroporous adsorption resin, first washes with water, then uses the alcoholic solution eluting of concentration 30%-80%, collects different concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract B;
(5) above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B are mixed, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
3. the preparation method of exhibition hair Herba delphinii grandiflori extract is according to claim 1:
(1) exhibition hair Herba delphinii grandiflori, with concentration 70% ethanol, as solvent, at 50 ℃ of warm macerating, extract, extraction time is 3 times, each extraction time is 4 hours, each solvent load, for 20 times of exhibition hair Herba delphinii grandiflori weight, filters, and obtains medicinal residues A and extracting solution, extracting solution reclaims ethanol, be concentrated into relative density d=1.10, filter, obtain medicinal liquid A;
(2) medicinal liquid A step (1) being obtained, by D101 macroporous adsorbent resin, first washes with water, then the alcoholic solution of using concentration 60% eluting successively, collects 60% concentration ethanol eluent, and concentrate drying, must open up a hair Herba delphinii grandiflori extract A;
(3) step (1) being obtained to medicinal residues A water is solvent, reflux, extract,, and extraction time is 3 times, and each extraction time is 2 hours, and each solvent load, for 10 times of exhibition hair Herba delphinii grandiflori weight, filters, and extracting solution is concentrated into relative density d=1.11, filters, and obtains medical liquid B;
(4) medical liquid B step (3) being obtained, by DM130 macroporous adsorbent resin, first washes with water, then uses the alcoholic solution eluting of concentration 70%, collects 70% concentration ethanol eluent, and concentrate drying must be opened up hair Herba delphinii grandiflori extract B;
(5) above-mentioned exhibition hair Herba delphinii grandiflori extract A, exhibition hair Herba delphinii grandiflori extract B are mixed, obtain exhibition hair Herba delphinii grandiflori extract of the present invention.
4. according to the preparation method of claim 1, exhibition hair Herba delphinii grandiflori extract claimed in claim 2, it is characterized in that: the nonpolar macroporous adsorption resin adopting is AB-8 macroporous adsorbent resin, D101 macroporous adsorbent resin; The polar macroporous adsorption resin adopting is DM130 macroporous adsorbent resin, ADS-3 macroporous adsorbent resin.
5. the treatment AIDS-treating medicine that exhibition hair Herba delphinii grandiflori extract according to claim 1 and chemical drugs or Chinese medicine or natural drug form.
6. exhibition hair Herba delphinii grandiflori extract A according to claim 1, the application of exhibition hair Herba delphinii grandiflori extract B in preparation treatment AIDS-treating medicine.
7. the treatment AIDS-treating medicine that exhibition hair Herba delphinii grandiflori extract A according to claim 1, exhibition hair Herba delphinii grandiflori extract B and chemical drugs or Chinese medicine or natural drug form.
8. according to claim 1, claim 2, exhibition claimed in claim 3 hair Herba delphinii grandiflori extract, by the various adjuvants that add pharmaceutics to allow, make the peroral dosage forms such as tablet on pharmaceutics, granule, capsule.
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| 丁立生等: "展毛翠雀花中的二萜生物碱 ", 《药学学报》 * |
| 丁立生等: "展毛翠雀花中的二萜生物碱", 《药学学报》, vol. 25, no. 06, 31 December 1990 (1990-12-31), pages 438 - 440 * |
| 任舒燕等: "展毛翠雀花根部生物碱的提取及抑菌试验 ", 《大连工业大学学报》 * |
| 任舒燕等: "展毛翠雀花根部生物碱的提取及抑菌试验", 《大连工业大学学报》, vol. 28, no. 04, 31 July 2009 (2009-07-31), pages 248 - 250 * |
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| CN110604795A (en) * | 2019-09-27 | 2019-12-24 | 山东佳硒雅生物有限公司 | Gynecological inflammation gel and preparation method thereof |
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