CN104510734A - Pharmaceutical composition for treating AIDS - Google Patents

Pharmaceutical composition for treating AIDS Download PDF

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CN104510734A
CN104510734A CN201410628729.3A CN201410628729A CN104510734A CN 104510734 A CN104510734 A CN 104510734A CN 201410628729 A CN201410628729 A CN 201410628729A CN 104510734 A CN104510734 A CN 104510734A
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pharmaceutical composition
weight portion
aids
treatment
deficiency syndrome
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孔倩倩
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Jinan Xingyi Medical Technology Co Ltd
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Jinan Xingyi Medical Technology Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/473Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1652Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2031Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

The invention relates to a pharmaceutical composition for treating AIDS. The pharmaceutical composition is prepared from raw materials of amentoflavone, magnoflorine, podophyllotoxin and gomisin G in certain proportion; and the pharmaceutical composition can be prepared into various dosage forms according to the conventional preparation process. The pharmaceutical composition provided by the invention has great significance to the preparation of medicaments for the treatment of AIDS.

Description

A kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS)
Technical field
The invention belongs to biomedicine field, relate to a kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS).
Background technology
Acquired immune deficiency syndrome (AIDS) is the new virus sexually transmitted disease found 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 heresy invasion and attack of epidemic disease, deficiency of vital QI and causing.Pathogenesis is mainly weakened defensive QI, and yang-energy damages, and internal organs are got involved, and causes that the deficiency of the lung is insufficiency of the spleen suffers 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, and the change of disease in evil poison enters, the dynamic change of just resisting with the heresy of body healthy energy is advancing of disease process.Infect early stage based on the domination of pathogen, mid-term " causes void because of real ", 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 be formed " disease ", and has difference " type " and " phase ".The traditional Chinese medical science has dialectical differential diagnosis of diseases to acquired immune deficiency syndrome (AIDS), the typing different diagnosis and treatment project 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 generally acknowledged curative effect certainly go through produce AIDS virus resisting Chinese medicine or Chinese medicine monomer compound.AIDS virus resisting plant amedica and Chinese medicine research mainly divide 3 kinds of approach, and the AIDS virus resisting Chinese medicinal plant medicine that smoking set obtains and composition thereof, some is in clinic trial.
Since HIV (human immunodeficiency virus) finds, use HIV (human immunodeficiency virus) cell culture and reverse transcriptase in the world, the ill vitro test method such as protease and intergrase, while extensive SCREENED COMPOUND, also plant and Chinese herbal medicine extract and composition thereof is screened in a large number, also studied some compound Chinese medicinal preparation, find the active drug of inhibiting HIV in vitro, the viremia of the suppressed simian immunodeficiency virus had (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.In recent years to the AIDS patients that laboratory diagnosis is made a definite diagnosis, adopt treatment by Chinese herbs, if matched group, at treatments period, periodic detection blood viral charge (HIV-RNA) and cd4 cell level, evaluation effect.There is report to improve symptom, improve immunity, mostly still in clinical verification.Enter clinical AntiHIV1 RT activity 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, HIV cell fusion is suppressed in cell culture, also resisiting influenza virus and SARS virus, the dead and pneumonopathy change of the pneumonia that experiment in vivo proves to protect influenza infection mice to cause; The CCl of protection mice 4toxic liver injury; Induce gamma interferon; There is parahormone effect.Japan's its intravenous administrations chronic hepatitis B conventional, also once tried out treatment AIDS patients, can suppress serum HIV-1-P24 antigen, raised 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) belong to Cucurbitaceae (Cucurbitaceae) for Chinese medicine Fructus Trichosanthis (Trichosanthes kirilowii), the main Chinese medicine ingredients of China's Chinese medicine compound for 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 toxalbumin of Profilin synthesis, 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 find P24 antigen and the RNA of HIV-1 in mononuclear phagocyte is cultivated, blood plasma HIV-1 can be suppressed in the intravenous injection of 3 simian acquired immunodeficiency syndrome virus (SIV) infected monkeys.The U.S. uses intravenous administrations AIDS patients in forest farm, and HIV-1-P24 antigen in the T lymphocyte that peripheral blood HIV-1 can be suppressed to infect and mononuclear phagocyte, makes CD4/ CD8 ratio slightly raise.Due to anaphylactic reaction can be caused dead, neurovirulent Mental Subnormality and nephrotoxicity reaction, clinical experiment stops.From Radix Trichosanthis, isolate other albumen TAP29 in recent years, molecular weight, at 29 kD, also have the effect suppressing HIV-1, but toxicity is less, not in clinic trial.In addition the bitter melon protein of Fructus Momordicae charantiae (MOmordica charantia) and the Radix Phytolaccae albumen (Pokeweed protein) etc. of Radix Phytolaccae (Phytolacca americana) have the effect suppressing HIV.
Hypericin: plant Herba Hyperici Monogyni (St. John Wort, Hypericum perforatum) its extract for treating depression of folk tradition, the active component proposed 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, in cell culture, suppress HIV, and its mechanism of action is undressing of blocking virus, and assembling and release, the effect of killing the virus, by blood brain barrier.Murine leukemia virus can be suppressed in cell culture to breed.The splenomegaly that murine leukemia virus infecting mouse causes can be suppressed in vivo, duck hepatitis B virus infection Sanguis Anas domestica also can be suppressed to ask viral DNA, and have broad spectrum antibiotic active.Once in treatment on probation of clinical I/II phase HIV sufferers, test had been stopped because there being light sensitization.
1992 year report the native compound that from Malaysian rainforest plant Calophyllum lanigerum be separated dextrorotation lane element A: dextrorotation lane element A(+Calanolide A), 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 in the responsive and drug resistance HIV-1 of the AZT of clinical separation effectively, and and AZT, NVP have synergism.In HIV hollow fiber pipe Mice Body, prove there is AIDS virus resisting effect in experimental model (HIV hollow fiber mouse model), can drug effect be strengthened with AZT use in conjunction.Complete synthesis, having carried out its clinical trial of I-II proves there is the therapeutic effect suppressing HIV-1 to infect, and toxicity is little, and side effect is light, has headache and inappetence etc., effective with AZT drug combination.Be the single plant component uniquely entering II phase clinical experiment at present, observing in checking curative effect, not yet ratify to produce.
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. is used for the treatment of numerical example AIDS patients clinical, can reduce blood-serum P 24 antigen.We prove that it has the effect suppressing HIV1-RT and suppress HIV-1 in cell culture.Study the effect of its 7 kinds of composition Chinese medicines respectively, find that only Radix Scutellariae water extract and composition baicalin (baicalin) thereof have and suppress HIV-1 effect, HIV1-RT is suppressed in vitro in cell free system, HIV-1 cytopathy is suppressed in human T-cell and peripheral blood lymphocytes cultivate, FLuorescent antigen and P24 antigen, in body, oral splenomegaly and the blood leukocytes of suppressing of murine leukemia virus infecting mouse raises.Japan Ono reports that noroxylin (baicalien) suppresses HIV1-RT.
In grind No. I: in grind No. I commodity such as (principal agent has Herba Violae, Radix Trichosanthis composition) and be called: Chinese mugwort
Gram electuary take heat-clearing and toxic substances removing as the rule for the treatment of, by Chinese medicine research institute of China prescription 1992-1993 in African Tanzania to the clinical practice of early metaphase acquired immune deficiency syndrome (AIDS), think to have and necessarily improve symptom, improve the effect of immunity.Laboratory proves that this medicine vitro inhibition hiv reverse transcriptase is active, simian acquired immunodeficiency syndrome poison infected monkey experimental therapy result is shown in body, plasma viral titre can be reduced, and cd4 cell number and CD4/CD8 ratio and T can be improved, bone-marrow-derived lymphocyte numerical value, inducement interferon and generation immunoloregulation function.Once in Africa and China's clinic trial, not yet clinical verification was ratified.
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.Experiment proves that this medicine shows simian acquired immunodeficiency syndrome poison infected monkey experimental therapy in human body, and medication 4-12 week can reduce plasma viral titre, P27 antigen, and can improve cd4 cell number, has activation to infected monkey lymphocyte.
Amentoflavone (amentoflavone): CAS 1617-53-4, molecular formula C 30h 18o 10, molecular weight 538.46, antifungal (Aspergillus fumigatus, Botrytis cinerea and powder green trichoderma bacterium), Nucleoside-diphosphatase inhibitor.
Magnoflorine (magnoflorine) also known as thalictrine, magnoflorine, Magnoflorine etc.CAS 2141-09-5, molecular formula C 20h 24nO 4, its iodide (C 20h 24nO 4.I) crystalline solid (by methanol+acetone), decomposition point 248 ~ 249 DEG C.Optical rotation+220.1 ° (methanol).Naturally to be present in the root street plant of ranunculaceae plant thick fruit Thalictrum aquilegifolium L. var. sibiricum Regel.Can chemosynthesis obtain.This product has the effects such as antiinflammatory, blood pressure lowering, antifertility.Formula containing this product has insecticidal action.The iodide of this product have antimicrobial and cytotoxicity.
Podophyllotoxin (podophyllotoxin): CAS 518-28-5, molecular formula C 22h 22o 8, molecular weight 414.41, physicochemical property: white, needle-shaped crystals powder.Be soluble in chloroform, acetone, ethyl acetate and benzene, dissolve in ethanol, ether, water insoluble.Podophyllotoxin is from XIAONIE section may apple---the wooden lipid antitumor composition that extracts the root of Chinese common sinopodophyllum rhi-zome (also known as chicken tongue element) and stem.For white crystalline powder, odorless, there is hygroscopicity.Chinese common sinopodophyllum rhi-zome is mainly distributed in the ground such as the Gansu Province of China.The podophyllotoxin extracted from Chinese common sinopodophyllum rhi-zome (also known as chicken tongue element) can make unguentum and tincture.Podophyllotoxin effectively can suppress herpesvirus, and the mitosis in T suppression cell mid-term, for toxicity sexually transmitted disease (STD).
Gomisin G. (gomisin G): CAS 62956-48-3, molecular formula C 30h 32o 9, molecular weight 536.57.Anti-AIDS.
4 kinds of medicines structures of pharmaceutical composition of the present invention are as follows:
Amentoflavone (amentoflavone) magnoflorine (magnoflorine)
Podophyllotoxin (podophyllotoxin) Gomisin G. (gomisin G).
Summary of the invention
The object of the invention is the deficiency overcoming background technology, a kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) is provided.
The present invention is achieved through the following technical solutions:
Of the present invention a kind of treat the crude drug of the pharmaceutical composition of acquired immune deficiency syndrome (AIDS) composition and weight portion be:
Amentoflavone 2-15 weight portion magnoflorine 2-15 weight portion podophyllotoxin 2-15 weight portion Gomisin G. 2-15 weight portion.
A kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) of the present invention can adopt the conventional method of galenic pharmacy to be prepared into tablet, capsule, drop pill.
A kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) of the present invention, is characterized in that being used for the treatment of acquired immune deficiency syndrome (AIDS).
The splenomegaly that drug composition oral provided by the invention can suppress FLV to cause.Spleen is the first target organs of virus, and the spleen of FLV infected mice increases weight large I quantitative response virus quantity, and therefore can medicine suppress virus, and spleen index is a directly perceived and index reliably.Spleen has abundant lymphocyte and macrophage, and they all participate in humoral immune reaction, so pharmaceutical composition can suppress splenomegaly in an experiment, shows it and not only has anti-FLV effect in body, also may have the effect improving humoral immune function.From the experimental result of amynologic index, pharmaceutical composition has good rise effect to cellular immunization, particularly when the body's immunity that retrovirus causes is low, performance is particularly remarkable, showing this pharmaceutical composition can enhancing body cellular immune function, suppressing the immunodeficiency that FLV causes, is a good immunomodulator.
Detailed description of the invention
Below by specific experiment example and embodiment, a kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) is described further, but is not limited to the present invention.
Embodiment 1: the pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS)
Composition and the weight portion of the crude drug of the pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) are:
Amentoflavone 5 weight portion magnoflorine 10 weight portion podophyllotoxin 8 weight portion Gomisin G. 12 weight portion.
Embodiment 2: the pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS)
Composition and the weight portion of the crude drug of the pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) are:
Amentoflavone 15 weight portion magnoflorine 2 weight portion podophyllotoxin 15 weight portion Gomisin G. 2 weight portion.
Embodiment 3: the pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS)
Composition and the weight portion of the crude drug of the pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) are:
Amentoflavone 2 weight portion magnoflorine 15 weight portion podophyllotoxin 2 weight portion Gomisin G. 15 weight portion.
Embodiment 4: the pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS)
Composition and the weight portion of the crude drug of the pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) are:
Amentoflavone 6 weight portion magnoflorine 7 weight portion podophyllotoxin 8 weight portion Gomisin G. 4 weight portion.
Embodiment 5: the preparation of tablet
Example 1 compositions 150g, adds starch 75g, mixing, granulates, dry, adds microcrystalline Cellulose 20g, magnesium stearate 2.5g, and mixing, is pressed into 1000, obtains present composition tablet.
Embodiment 6: the preparation of capsule
Example 2 compositions 165g, adds starch 65g, mixing, granulates, and dry, granulate, adds appropriate magnesium stearate, and mixing, obtains present composition capsule by encapsulated 1000.
Embodiment 7: the preparation of drop pill
Taking polyethylene glycol 6000 200g water-bath (80 DEG C) heating boils molten, add embodiment 3 compositions 50g, stirring, is coolant with liquid paraffin, puts in glass tubing (4*80cm), chilling temperature is 10 DEG C, drip internal-and external diameter is 7.0/2.0 (mm/mm), and drip is 2cm apart from liquid level, drips speed with per minute 50 for optimum condition, blot the condensing agent on drop pill surface with cotton, obtain present composition drop pill.
Experimental example 1: pharmaceutical composition is to acquired immune deficiency syndrome (AIDS) mice therapeutical effect
1. materials and methods
Medicine: embodiment 1 pharmaceutical composition, embodiment 2 pharmaceutical composition, embodiment 3 pharmaceutical composition, embodiment 4 pharmaceutical composition, lot number is respectively: 20111010,20111011,20111012,20111013, dissolve with the dimethyl sulfoxide of 30g/L (DMSO) during test, then with distilled water diluting to desired concn; Positive control medicine zidovudine (AZT) is produced by Xiamen Pharmaceutical Factory, and lot number is 090907.
Animal: only, female, weight l3-15 g, is provided by Guangdong Province's Experimental Animal Center, the quality certification number SPF level BALB/C mice 5O: check and affirm word 2011A013 in SCXK (Guangdong) 2009-0002 Guangdong.
Seed culture of viruses: Friend type murine leukemia virus (FriendLeukemia virus, FLV) draw from American Type culture collecting center (American Typical Culture Centre, ATCC), after mice goes down to posterity enhancing virulence, make 100 g/L spleen suspensions ,-70 DEG C frozen for subsequent use.
Main agents: the two labeling antibody of PE/Cy5 anti-mouse CD3e monoclonal; PE/Cy5 Mouse IgG1, K Isotype Ctrl Isotype control; FITC anti-mouse CD4/PE anti-mouse CD8a monoclonal list labeling antibody; FITC Mouse IgG1, K Isotype Ctrl/PEMouse IgG1, K Isotype Ctrl Isotype control, is more than U.S. Biolegend Products.
Virus median infective dose (ID 50) titration: lumbar injection FLV, makes 0.1g/L spleen suspension, collects spleen suspension and press literature method calculating ID 50, with 60 times of ID during experiment 50for the experimental concentration of mouse model of AIDS.
Pharmaceutical composition causes the inhibitory action of mice spleen enlargement to FLV: 70 mices are divided into normal group, model group, embodiment 1 pharmaceutical composition group, embodiment 2 pharmaceutical composition group, embodiment 3 pharmaceutical composition group, embodiment 4 pharmaceutical composition group, AZT group, often organize each 10; Except normal group, all adopt FLV lumbar injection infecting mouse.Normal group and model group every day are with a distilled water 0.2mL/ gavage, embodiment 1 pharmaceutical composition group, embodiment 2 pharmaceutical composition group, embodiment 3 pharmaceutical composition group, embodiment 4 pharmaceutical composition group dosage are 20mg/kg, AZT group dosage is 100mg/kg, all be made into 2mL solution with distilled water, after virus attack, l d starts with the administration of gavage mode, 0.2mL/, 1 time/d, successive administration 21d; Cut open after administration 21d and kill mice, calculate mouse spleen index and spleen index suppression ratio, spleen index (mass ratio) ω spleen=m spleen(mg)/m body(g), p spleen index suppresses=(ω on average, model groupon average, administration group)/ω on average, model group× 100%.Obtained experimental data statistic software SPSS 10.0 is analyzed, compares between each group and adopt one factor analysis of variance (LSD).
Hemogram checking: pluck eyeball anticoagulant and get blood, carries out erythrocyte (RBC) counting, leukocyte (WBC) counting with full-automatic blood counting instrument.
Impact on cellular immune function: measure mouse thymus index (mass ratio), ω thymus=m thymus(mg)/m body(g); T lymphocyte subsets of peripheral blood horizontal detection, adopts cells were tested by flow cytometry BALB/C mice T lymphocyte subsets CD3 +, CD4 +, CD8 +, CD4 +/ CD8 +level.
2. result
2.1 each groups cause the inhibiting comparison of mice spleen enlargement to FLV
The spleen index of each pharmaceutical composition group has significant difference (P<0.05) compared with model group, it is inhibited that display pharmaceutical composition causes mice spleen enlargement to FLV, and suppression ratio is respectively: 78.45%, 73.56%, 67.54%, 65.80%.The results are shown in Table 1.
The each pharmaceutical composition of table 1 is to the inhibitory action of FLV infecting mouse splenomegaly
1.: P<0.05, 2.: P<0.0l, compares with Normal group; 3.: P<0.05, 4.: P<0.0l, compares with model group (lower same).
The comparison of 2.2 each group cellular immune functions
Each pharmaceutical composition group thymus is better protected.Do not occur obvious atrophy, the decline of the thymus index that can cause after antagonism viral infection, shows good immanoprotection action.Periphery blood T lymphocyte analyzes (TLC) display, and each pharmaceutical composition can significantly improve peripheral blood CD3 +, CD4 +, CD8 +t lymphocyte level, and to a certain degree can adjust CD4 +/ CD8 +ratio trend is normal.The results are shown in Table 2.
The each pharmaceutical composition of table 2 is on the impact of the cellular immune function of FLV infecting mouse
This experimental result shows, the splenomegaly that each drug composition oral of the present invention can suppress FLV to cause.Spleen is the first target organs of virus, and the spleen of FLV infected mice increases weight large I quantitative response virus quantity, and therefore can medicine suppress virus, and spleen index is a directly perceived and index reliably.Spleen has abundant lymphocyte and macrophage, and they all participate in humoral immune reaction, so pharmaceutical composition can suppress splenomegaly in an experiment, shows it and not only has anti-FLV effect in body, also may have the effect improving humoral immune function.From the experimental result of amynologic index, pharmaceutical composition has good rise effect to cellular immunization, particularly when the body's immunity that retrovirus causes is low, performance is particularly remarkable, showing each pharmaceutical composition can enhancing body cellular immune function, suppressing the immunodeficiency that FLV causes, is a good immunomodulator.

Claims (7)

1. treat a pharmaceutical composition for acquired immune deficiency syndrome (AIDS), it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Amentoflavone 2-15 weight portion magnoflorine 2-15 weight portion podophyllotoxin 2-15 weight portion Gomisin G. 2-15 weight portion.
2. according to claim 1: a kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS), it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Amentoflavone 5 weight portion magnoflorine 10 weight portion podophyllotoxin 8 weight portion Gomisin G. 12 weight portion.
3. according to claim 1: a kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS), it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Amentoflavone 15 weight portion magnoflorine 2 weight portion podophyllotoxin 15 weight portion Gomisin G. 2 weight portion.
4. according to claim 1: a kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS), it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Amentoflavone 2 weight portion magnoflorine 15 weight portion podophyllotoxin 2 weight portion Gomisin G. 15 weight portion.
5. according to claim 1: a kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS), it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Amentoflavone 6 weight portion magnoflorine 7 weight portion podophyllotoxin 8 weight portion Gomisin G. 4 weight portion.
6. a kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) according to claim 1, can adopt the conventional method of galenic pharmacy to be prepared into tablet, capsule, drop pill.
7. a kind of pharmaceutical composition for the treatment of acquired immune deficiency syndrome (AIDS) according to claim 1, is characterized in that being used for the treatment of acquired immune deficiency syndrome (AIDS).
CN201410628729.3A 2014-11-11 2014-11-11 Pharmaceutical composition for treating AIDS Pending CN104510734A (en)

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Citations (1)

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Publication number Priority date Publication date Assignee Title
CN1587266A (en) * 2004-07-14 2005-03-02 华东理工大学 Improved process for preparing podophyllotoxin from Chinese podophyllum root

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
CN1587266A (en) * 2004-07-14 2005-03-02 华东理工大学 Improved process for preparing podophyllotoxin from Chinese podophyllum root

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DAO-FENG CHEN ET AL: "Anti-AIDS Agents-XXVI.Structure-Activity Correlations of Gomisin-G-Related Anti-HIV Lignans From Kadsura interior and of Related Synthetic Analogues", 《BIOORGANIC & MEDICINAL CHEMISTRY》 *
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