CN102885845A - Application of Houttuynoid B in medicament for resisting tubercle bacillus - Google Patents

Abstract

The invention discloses an application of Houttuynoid B in the preparation of a medicament for resisting tubercle bacillus. Aiming at the current situation that the disease incidence and the mortality rate of tuberculosis have ascending trends due to high disease incidence of tuberculosis and the appearance of tubercle bacillus multiple drug-resistant strains at present, Houttuynoid B has the characteristic of obviously inhibiting the activity of tubercle bacillus and has good application prospect. The application of Houttuynoid B in the preparation of a medicament for resisting tubercle bacillus is firstly disclosed; since the skeleton type belongs to an entirely new skeleton type and the activity for inhibiting tubercle bacillus is previously unimagined high without any possibility of giving out revelation by other compounds, the application has outstanding substantial characteristics; and simultaneously, the application for preventing and treating tubercle bacillus infection is obviously advanced.

Description

The application of Houttuynoid B in anti-tubercle bacillus drugs

Technical field

The present invention relates to the medical compounds application, be specifically related to the application of Houttuynoid B in the preparation anti-tubercle bacillus drugs.

Background technology

In recent years global morbidity lungy is increases trend, estimate according to the World Health Organization (WHO), the whole world is subjected to the population of mycobacterium tuberculosis (Mycobacterium tuberculosis, MTB) infection to account for 1/3rd of world population at present, and wherein the infected of 5 ~ 10% becomes tuberculosis patient.Active tuberculosis patient 1,300,000 examples every year appears in China, about 600,000 examples of infectiousness pulmonary tuberculosis wherein, and wherein about 600,000 examples of infectiousness pulmonary tuberculosis are one of the high burden of global tuberculosis countries.

Come out one after another from antituberculotics, make treatment lungy play epoch-making variation.Yet because the treatment of tuberculosis patient management standard very not still, irregular chemotherapy, the abuse antituberculotics makes the drug resistance of tuberculosis situation day by day serious, and chemical sproof variation more trends towards simultaneously drug resistance of multi-medicament, and this causes very big difficulty for preventing and controlling lungy.Therefore seek new antituberculotics, the antituberculotics of especially anti-multidrug resistance is to the protection people's health, and is significant.

Summary of the invention

The compound H outtuynoid B that the present invention relates to is one and delivered (Chen in 2012, S. D. et al., 2012. Houttuynoid B_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.) New skeleton compound, this chemical compound has brand-new framework types, present purposes only relates to anti-herpes simplex virus activity (Chen, S. D. et al., 2012. Houttuynoid B_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.), belong to open first for the purposes of the Houttuynoid B that the present invention relates in preparation treatment anti-tubercle bacillus drugs, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for tulase, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, the control that is used for simultaneously tubercle bacillus affection obviously has significant progress.

Summary of the invention

The object of the invention is to provides the application of Houttuynoid B in the preparation anti-tubercle bacillus drugs according to not finding that it has the present situation of the report of tuberculosis activity in the existing Houttuynoid B research.

Described compound H outtuynoid B structure is shown in formula I:

The object of the invention is achieved by the following technical programs:

The inventor does the examination bacterial strain with bacillus calmette-guerin vaccine first, adopt disk diffusion method that the anti-tubercle bacillus activity of Houttuynoid B is carried out preliminary test, result according to preliminary test, the present invention use again the solid medium By Dilution this chemical compound to bacillus calmette-guerin vaccine, the minimal inhibitory concentration of three kinds of tulases of the H37Rv strain of mycobacterium tuberculosis type strain and substance of medicines-resistant branched tubercle bacillus (MDR MTB), experimental result confirms that Houttuynoid B has very strong anti-tubercle bacillus and the anti-drug resistance tulase is active, can be used as the lead compound for the treatment of tubercle bacillus affection disease, also can be used for preparation treatment tuberculosis medicine.

Compared with prior art, the present invention has following beneficial effect:

1. the invention provides a kind of Houttuynoid B that can be used for the sick treatment of tuberculosis, thereby enlarged the kind of anti-tubercle bacillus drugs;

2. the appearance of, tubercule bacillus multiple antibiotic resistant strain high for present incidence of tuberculosis and HIV (human immunodeficiency virus) double infection, make incidence of tuberculosis and mortality rate present situation in rising trend, the present invention finds that Houttuynoid B has the characteristics of anti-tubercle bacillus and drug resistance tulase activity, can be used for the preparation of antituberculotics, have boundless application prospect;

3. the purposes of the Houttuynoid B that the present invention relates in preparation treatment anti-tubercle bacillus drugs belongs to open first, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for tulase, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, the control that is used for simultaneously tubercle bacillus affection obviously has significant progress.

The specific embodiment

The preparation method of compound H outtuynoid B involved in the present invention is referring to document (Chen, S. D. et al., 2012. Houttuynoid B_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.).

The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subjected to any restriction of specific embodiment, but limited by claim.

Embodiment 1: the preparation of compound H outtuynoid B tablet involved in the present invention:

Get 20 and digest compound Houttuynoid B, add conventional adjuvant 180 grams of preparation tablet, mixing, conventional tablet machine are made 1000.

Embodiment 2: the preparation of compound H outtuynoid B capsule involved in the present invention:

Get 20 and digest compound Houttuynoid B, add conventional adjuvant such as starch 180 grams of preparation capsule, mixing is encapsulatedly made 1000.

Further specify its pharmaceutically active below by pharmacodynamic experiment.

The experimental example 1 anti-bacillus calmette-guerin vaccine of solid medium By Dilution Houttuynoid B (BCG) absolute concentration

Scraping bacillus calmette-guerin vaccine culture from the inclined-plane, join in the 3ml Middlebrook7H9 broth bouillon, add a small amount of bead, screw test tube cap, high vibration grinds on the vortex oscillation device, with standard Maxwell opacity tube (MacFarland No.1) than turbid, namely be made into bacillus calmette-guerin vaccine (BCG) bacteria suspension of 1mg/ml.

Houttuynoid B is made into the stock solution of high concentration with DMSO, dilute stock solution to desired concn with the aseptic ultra-pure water of the tween 80 that contains 5%, the Houttuynoid B that dilution is good joins 4ml Middlebrook7H11 agar culture medium (this culture medium 121 ℃ of high pressure steam sterilizations 15 minutes, be cooled to 50 ~ 55 ℃) by required dosage, mixing, make and contain Houttuynoid B, concentration is respectively 6.0 ug/ml, 4.0 ug/ml, 3.0 ug/ml, 2.0 ug/ml, 1.5 ug/ml, 1.0 ug/ml, 0.75 ug/ml, the isocyatic slant medium of 0.5 ug/ml.

Be that bacillus calmette-guerin vaccine (BCG) bacteria suspension of 1 mg/ml dips ring of numbers with inoculating loop with concentration, be inoculated in respectively on the culture medium and blank medium slant that contains Houttuynoid B series concentration, place 37 ℃ to cultivate for 4 ~ 8 weeks, the observation experiment result, the result is as shown in table 1.

Culture medium commonly used when used Middlebrook7H9 broth bouillon and Middlebrook7H11 agar culture medium carry out the tulase cultivation for those skilled in the art in the present embodiment, its prescription adopts conventional formulation to get final product.

Experimental example 2 solid medium By Dilution Houttuynoid B Killing Mycobacterium Tuberculosis type strain H37Rv strain absolute concentrations

Scraping mycobacterium tuberculosis type strain H37Rv strain culture from the inclined-plane, join in the 3 ml Middlebrook7H9 broth bouillons, add a small amount of bead, screw test tube cap, high vibration grinds on the vortex oscillation device, with standard Maxwell opacity tube (MacFarland No.1) than turbid, namely be made into the H37Rv strain bacteria suspension of 1 mg/ml.

Houttuynoid B is made into respectively the stock solution of high concentration with DMSO, dilute stock solution to desired concn with the aseptic ultra-pure water of the tween 80 that contains 5%, the Houttuynoid B that dilution is good joins 4ml Middlebrook7H11 agar culture medium by required dosage, and (this culture medium is 121 ℃ of high pressure steam sterilizations 15 minutes, be cooled to 50 ~ 55 ℃), mixing, make and contain Houttuynoid B, concentration is respectively 6.0 ug/ml, 4.0 ug/ml, 3.0 ug/ml, 2.0 ug/ml, 1.5 ug/ml, 1.0 ug/ml, 0.75 ug/ml, the isocyatic slant medium of 0.5 ug/ml.

Be that the H37Rv strain bacteria suspension of 1mg/ml dips ring of numbers with inoculating loop with concentration, be inoculated in respectively on the culture medium and blank medium slant that contains Houttuynoid B series concentration, place 37 ℃ to cultivate for 4 ~ 8 weeks, the observation experiment result, the result is as shown in table 1.

The clinical separation of the experimental example 3 solid medium By Dilution Houttuynoid B tuberculosis mycobacteriums MTB of anti-ISRE strain absolute concentration

The clinical separation of the scraping mycobacterium tuberculosis MTB of anti-ISRE strain (anti-isoniazid, streptomycin, rifampicin, the clinical detached dowel of ethambutol mycobacterium tuberculosis) culture from the inclined-plane, join in the 3ml Middlebrook7H9 broth bouillon, add a small amount of bead, screw test tube cap, high vibration grinds on the vortex oscillation device, with standard Maxwell opacity tube (MacFarland No.1) than turbid, namely be made into the bacteria suspension of 1mg/ml.

Houttuynoid B is made into respectively the stock solution of high concentration with DMSO, dilute stock solution to desired concn with the aseptic ultra-pure water of the tween 80 that contains 5%, the Houttuynoid B that dilution is good joins 4ml Middlebrook7H11 agar culture medium by required dosage, and (this culture medium is 121 ℃ of high pressure steam sterilizations 15 minutes, be cooled to 50 ~ 55 ℃), mixing, make and contain Houttuynoid B, concentration is respectively 6.0 ug/ml, 4.0 ug/ml, 3.0 ug/ml, 2.0 ug/ml, 1.5 ug/ml, 1.0 ug/ml, 0.75 ug/ml, the isocyatic slant medium of 0.5 ug/ml.

Be that the clinical separation of the mycobacterium tuberculosis MTB of the anti-ISRE strain bacteria suspension of 1mg/ml dips ring of numbers with inoculating loop with concentration, be inoculated in respectively on the culture medium and blank medium slant that contains Houttuynoid B series concentration, place 37 ℃ to cultivate for 4 ~ 8 weeks, the observation experiment result, the result is as shown in table 1.

Table 1 solid medium By Dilution Houttuynoid B anti-tubercle bacillus absolute concentration result

Conclusion: Houttuynoid B has very strong anti-tubercle bacillus and the anti-drug resistance tulase is active, can be used as the lead compound for the treatment of tubercle bacillus affection disease, also can be used for preparation treatment tuberculosis medicine.

Claims (1)

1.Houttuynoid the application of B in anti-tubercle bacillus drugs, described compound H outtuynoid B structure as Formula IShown in:

Formula I.