CN100344747C - Sulfated NF1 granulose-anti-AIDS medicine and its preparing method - Google Patents

Abstract

The present invention belongs to the technical field of biologic pharmacy. Based on the patent 'Purificationn and utilization of distilled grains', Fengwei mushroom NF1 strains are screened and cultured; fermentation liquid is obtained in a distilled grain culture medium and via liquid submerged fermentation, separated and purified to obtain NF1 polysaccharide which is sulfated into sulfated NF1 polysaccharide further filled in enteric capsules to obtain an anti-AIDS medicine in the form of sulfated NF1 polysaccharide enteric capsules. The LD50 acute toxicity test result is 10007 mg/kg, extracorporeal detection proves the inhibiting rate of 94.02 % for HIV-RT (reverse transcriptase activity), and oral intracorporeal detection probes treating effect on AIDS patients with attack symptoms.

Description

Sulfation NF 1Granulose---anti-acquired immunodeficiency syndrome drug and preparation method thereof

One, technical field

The invention belongs to biological pharmacy technical field.

Two, background technology

(acquired immunodeficiency syndrome AIDS) is the disease that is called human immunodeficiency virus (human immunodeficiency virus HIV) infection and is suffered from by a kind of to acquired immune deficiency syndrome (AIDS).Blood examination HIV positive person then is considered as HIV the infected.After human body was infected by HIV, it had attacked the CD among the t lymphocyte subset group in the body ₄And CD ₈, CD ₄Sum is less than 200～500/mm ³, CD ₄/ CD ₈Less than 1, thereby destroyed the immunity system of human body, therefore to other bacterium and the infection of virus have no resistibility and suffer from various symptoms disease (as lose weight, be in a cold sweat in fever, night for a long time, fash, diarrhoea, health are tired, lymph enlargement etc., what have suffers from dementia because of brain cell is subjected to the HIV damage), if can in time treat, then can prolong life,, then cause death as untimely treatment.

Over year, sulfated polysaccharides at home and abroad is subject to people's attention as the new anti-AIDS medicine of a class surplus in the of nearly ten.It is a class chemical structure complexity, and biological activity is various, the biologically active substance of structure activity relationship distinctness.

Sulfated polysaccharides has the adhesion of interference HIV to the host target cell, suppress the antigenic expression of HIV, suppress plasmodial formation, the activity that suppresses hiv reverse transcriptase, biological activitys such as raise immunity, the sulfate radical quantity of being hung on these biological activity degree and its polysaccharide is relevant, also relevant with the space structure of sulfated polysaccharides.Except the side effect of blood coagulation resisting function, find no new side effect so far.

Abroad, the xylan sulfuric ester of former federal republic of germany Bayer in 1987 and Hoechst company joint research and development synthetic, after this U.S.'s artificial synthetic piperylene sulfuric ester and sulfation β-1, the 3-D dextran is clinic trial all, all obtained satisfied result, except that blood coagulation resisting function, do not find new side effect.At home, Chinese Academy of Sciences's Shanghai medicine the side for many years, Xiang Daobin etc. has deep research to sulfated polysaccharides, but do not see the report that is useful on the treatment acquired immune deficiency syndrome (AIDS) so far.

Three, summary of the invention

The objective of the invention is to develop a kind of medicine that can prevent and treat acquired immune deficiency syndrome (AIDS).

(patent No.: on the basis 85 1 04057.8), Pleurotus sajor-caju NF is cultivated in screening in patent of invention " purification of vinasse with utilize method " ₁Bacterial strain is by " China Committee for Culture Collection of Microorganisms, common micro-organisms " center " preservation (NF ₁The preserving number of bacterial strain is CGMCC NO.0852, and preservation date is on December 9th, 2002), as substratum, inoculate NF with vinasse ₁Bacterial strain through the liquid submerged fermentation engineering method, obtains fermented liquid, and separation, purifying obtain NF from fermented liquid ₁Granulose detects its sugar degree with grace ketone method, and its yield is 2g/1000ml, and detecting its major ingredient through analytic centre of Nanjing University infrared spectra is β-1, and 3-dextran (See Attachment 1) obtains sulfation NF with its sulfonation reaction ₁Granulose, according to C.R.Ricketts, " BiochemistryJournal " Vol.51 report is identified its degree.With sulfation NF ₁Granulose pours into enteric coated capsule, becomes sulfation NF ₁The granulose enteric coated capsule is the medicine that prevents and treat acquired immune deficiency syndrome (AIDS).Free from environmental pollution in the whole process of preparation, need not additional environmental protection abatement equipment.

Sulfation NF ₁The granulose capsule, through Jiangsu Province's drug abuse test institute, its result of the acute toxicity test of mouse oral administration is LD ₅₀=10007mg/kg, visual inspection, all internal organs show no obvious abnormalities (seeing Appendix two).Through the Chinese Academy of Medical Sciences, China Concord Medical Science University, Viral Laboratory, Institute of Medicinal Biological Technique, prominent domestic virusology expert Chen Hongshan researcher's design, check, this medicine (NFS ₁) be 94.02% to the inhibiting rate of HIV-1RT (reversed transcriptive enzyme), the NFS that does simultaneously ₂, because of the relative NFS of sulfur-bearing acid group amount ₁Few, its inhibiting rate is 71.63% (seeing Appendix three).Through Kunming, Yunnan Province property CDC to the oral sulfation NF of 5 routine AIDS patients (volunteer) ₁Granulose enteric coated capsule (its dosage is: 0.3g/ grain, 5/time, 2 times/day), 6 days by a definite date, and carry out CD in its oral front and back ₄And CD ₈Detection, its result shows that this medicine has result of treatment (seeing Appendix four) to the frank patient of AIDS.

The prepared sulfation NF of the present invention ₁The raw material of granulose is vinasse, uses liquid submerged fermentation method, and whole preparation process is simple relatively, so cost is low, and Zhi Bei medicine valency is also cheap relatively thus.And the domestic and international medicine of preparation anti-AIDS commonly used, with extracting method in artificial synthesis and the brown alga etc., its technology relative complex, so the medicine high price is expensive.

Also because of preparation sulfation NF ₁The raw material of granulose and method are with different both at home and abroad, so the space structure of its major ingredient also can be different, and according to the structure activity relationship principle of sulfated polysaccharides, the effect of this pharmacological agent acquired immune deficiency syndrome (AIDS) also can be with different both at home and abroad.

Sulfation NF ₁Granulose can further be made deep development, studies show that sulfation NF according to we are existing ₁That granulose can prepare is hypoglycemic, the raw material of reducing blood-fat and treatment liver cancer medicine.

Four, specific embodiments

Get 14 kilograms of sucrose, 2 kilograms of Semen Maydis powder, wheat bran adds Ca (OH) for 5 kilograms ₂Auxiliary materials and mixing is transferred about PH to 6, and said mixture is added in one ton of fermentor tank after empty having disappeared, and pressure is 15 kilograms when real disappearing, and temperature is 125 ℃, last 40 minutes after, when jar temperature drop to 30 ℃, add Pleurotus sajor-caju NF ₁Bacterial strain, its weight is about 100 kilograms liquid spawn, and making fermentation volume is 1 ton, and through temperature control to 30 ℃, pressure is 0.5 normal atmosphere, promptly finishes through fermentation in 3 days.Emit fermented liquid from jar, after filtration, obtain residue (comprising mycelium), make feed and sell, remaining liquid is condensed into 10% of original volume through decompression, adds in this concentrated solution then that alcohol precipitation separates, purifying obtains NF ₁Granulose detects polysaccharide content with grace ketone method.This polysaccharide is obtained sulfation NF with chlorsulfonic acid-pyridine method sulfonation reaction method (the unnecessary pyridine entry of sulfonation reaction is reclaimed) ₁Granulose is identified its degree with C.R.Rickett report method, at last it is fed into enteric coated capsule, promptly becomes sulfation NF ₁The polysaccharide intestines are used colloidal sol capsule, the just medicine of anti-AIDS always.

Claims (3)

1, a kind of Pleurotus sajor-caju NF ₁Bacterial strain (Pleurotus sojorcaju), its preserving number is CGMCC No.0852, preparation sulfation NF ₁Granulose, the major ingredient that it is characterized in that this polysaccharide is β-1,3 dextran, and turns to sulfation .NF through sulfuric acid ₁Granulose.

2, according to the described sulfation NF of claim 1 ₁The preparation method of granulose is characterized in that with sucrose, Semen Maydis powder, wheat bran be culture medium inoculated NF ₁Bacterial strain obtains fermented liquid through liquid submerged fermentation method, with this separate, purifying obtains NF ₁Granulose changes formation sulfation NF through sulfonation reaction with this polysaccharide again ₁Granulose.

3, according to the described sulfation NF of claim 1 ₁The application of granulose in preparation prevention and treatment AIDS-treating medicine.