CN105412097A - Application of Leuconoxine in preparation of antituberculin drug - Google Patents
Application of Leuconoxine in preparation of antituberculin drug Download PDFInfo
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- CN105412097A CN105412097A CN201510939329.9A CN201510939329A CN105412097A CN 105412097 A CN105412097 A CN 105412097A CN 201510939329 A CN201510939329 A CN 201510939329A CN 105412097 A CN105412097 A CN 105412097A
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- leuconoxine
- tubercle bacillus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic 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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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- 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)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention discloses an application of Leuconoxine in preparation of an antituberculin drug. Aiming at the situation that morbidity and mortality of tuberculosis are on the rise due to high morbidity of tuberculosis currently and occurrence of multi-drug-resistant strains of tubercle bacillus, the research shows that the Leuconoxine has the remarkable tubercle bacillus inhibition activity and has the good application prospect.
Description
Technical field
The present invention relates to the novelty teabag of compound L euconoxine, particularly relate to the application of Leuconoxine in preparation treatment anti-tubercle bacillus drugs.
Background technology
Come out one after another from antituberculotics, make treatment lungy play epoch-making change.But due to the Case management still not very specification of tuberculosis patient, irregular chemotherapy, abuse antituberculotics, makes drug resistance of tuberculosis situation day by day serious, and the change of drug resistance more trends towards multi-medicament drug resistance simultaneously, this causes extreme difficulties to preventing and controlling lungy.Therefore find new antituberculotics, the antituberculotics of especially anti-multidrug resistance is to protection people's health, significant.
The compound L euconoxine that the present invention relates to is one and delivers (AtsushiUmehara in 2014, etal., TotalSynthesesofLeuconoxine, LeuconodineB, andMelodinineEbyOxidativeCyclicAminalFormationandDiaster eoselectiveRing-ClosingMetathesis.Org.Lett.2014, 16, noval chemical compound 2526-2529.), this compound has brand-new framework types (AtsushiUmehara, etal., TotalSynthesesofLeuconoxine, LeuconodineB, andMelodinineEbyOxidativeCyclicAminalFormationandDiaster eoselectiveRing-ClosingMetathesis.Org.Lett.2014, 16, 2526-2529.), the purposes of the Leuconoxine that the present invention relates in preparation treatment anti-tubercle bacillus drugs is belonged to first public.
Summary of the invention
The object of the invention is to not find that it has the present situation of the report of anti-anti-tubercle bacillus activity according in existing Leuconoxine research, provide the application of Leuconoxine in the anti-anti-tubercle bacillus drugs of preparation.
Described compound L euconoxine structure is as shown in formula I:
Described Leuconoxine is preparing the application in anti-tubercle bacillus drugs, and mycobacterium tuberculosis strain is mycobacterium tuberculosis type strain H37Rv.
A kind of anti-tubercle bacillus drugs, be that active component interpolation adjuvant is prepared from by Leuconoxine, preparation method, for getting 5 g of compound Leuconoxine, adds 195 grams, dextrin, and mixing, Conventional compression makes 1000.
A kind of anti-tubercle bacillus drugs, be that active component adds adjuvant and is prepared from by Leuconoxine, preparation method, for getting 5 g of compound Leuconoxine, adds starch 195 grams, mixing, encapsulatedly makes 1000.
Inventor first does examination bacterial strain with bacillus calmette-guerin vaccine, the anti-tubercle bacillus activity of disk diffusion method to Leuconoxine is adopted to carry out preliminary test, according to the result of preliminary test, the present invention uses this compound of solid medium By Dilution to bacillus calmette-guerin vaccine again, the minimal inhibitory concentration of the H37Rv strain of mycobacterium tuberculosis type strain and substance of medicines-resistant branched tubercle bacillus (MDRMTB) three kinds of tulases, experimental result confirms that Leuconoxine has very strong anti-tubercle bacillus and 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 tubercular drugs.
Compared with prior art, the present invention has following beneficial effect:
1. the invention provides a kind of Leuconoxine that can be used for antituberculosis treatment, thus expand the kind of anti-tubercle bacillus drugs; The present invention finds that Leuconoxine has the feature of anti-tubercle bacillus and drug resistant M bacterium activity, can be used for the preparation of antituberculotics, has boundless application prospect;
2. the purposes of the Leuconoxine that the present invention relates in preparation treatment anti-tubercle bacillus drugs belongs to first public, because framework types belongs to brand-new framework types, and it is unexpectedly strong for tulase inhibit activities, there is not the possibility being provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, the control simultaneously for tubercle bacillus affection obviously has significant progress.
Detailed description of the invention
The preparation method of compound L euconoxine involved in the present invention is see document (AtsushiUmehara, etal., TotalSynthesesofLeuconoxine, LeuconodineB, andMelodinineEbyOxidativeCyclicAminalFormationandDiaster eoselectiveRing-ClosingMetathesis.Org.Lett.2014,16,2526-2529.)
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by any restriction of specific embodiment, but be limited by claim.
Embodiment 1: the preparation of compound L euconoxine tablet involved in the present invention:
Get 5 g of compound Leuconoxine, add 195 grams, dextrin, mixing, Conventional compression makes 1000.
Embodiment 2: the preparation of compound L euconoxine capsule involved in the present invention:
Get 5 g of compound Leuconoxine, add starch 195 grams, mixing, encapsulatedly makes 1000.
Experimental example 1: the anti-bacillus calmette-guerin vaccine of solid medium By Dilution Leuconoxine (BCG) absolute concentration
Scraping BCG cultures from inclined-plane, join in 3mlMiddlebrook7H9 broth bouillon, add a small amount of bead, screw test tube cap, high vibration grinding in vortex oscillator, with standard Maxwell opacity tube (MacFarlandNo.1) than turbid, be namely made into bacillus calmette-guerin vaccine (BCG) bacteria suspension of 1mg/ml.
Leuconoxine DMSO is made into the stock solution of high concentration, by the tween 80 aseptic ultra-pure water dilution stock solution containing 5% to desired concn, the Leuconoxine diluted is joined 4mlMiddlebrook7H11 agar culture medium (this culture medium 121 DEG C of high pressure steam sterilizations 15 minutes, be cooled to 50 ~ 55 DEG C) by required dosage, mixing, make containing Leuconoxine, concentration is respectively 6.0ug/ml, 4.0ug/ml, 3.0ug/ml, 2.0ug/ml, 1.5ug/ml, 1.0ug/ml, the isocyatic slant medium of 0.75ug/ml, 0.5ug/ml.
Be that bacillus calmette-guerin vaccine (BCG) the bacteria suspension inoculating loop of 1mg/ml dips ring of numbers by concentration, be inoculated in containing in the culture medium of Leuconoxine series concentration and blank medium slant respectively, be placed in 37 DEG C to cultivate 4 ~ 8 weeks, observation experiment result, result is as shown in table 1.
In the present embodiment, Middlebrook7H9 broth bouillon used and Middlebrook7H11 agar culture medium are the conventional culture medium that those skilled in the art carry out when tulase is cultivated, and its formula adopts conventional formulation.
Experimental example 2 solid medium By Dilution Leuconoxine Killing Mycobacterium Tuberculosis type strain H37Rv strain absolute concentration
Scraping mycobacterium tuberculosis type strain H37Rv strain culture from inclined-plane, join in 3mlMiddlebrook7H9 broth bouillon, add a small amount of bead, screw test tube cap, high vibration grinding in vortex oscillator, with standard Maxwell opacity tube (MacFarlandNo.1) than turbid, be namely made into the H37Rv strain bacteria suspension of 1mg/ml.
Leuconoxine is made into respectively the stock solution of high concentration with DMSO, by the tween 80 aseptic ultra-pure water dilution stock solution containing 5% to desired concn, the Leuconoxine diluted is joined 4mlMiddlebrook7H11 agar culture medium (this culture medium 121 DEG C of high pressure steam sterilizations 15 minutes, be cooled to 50 ~ 55 DEG C) by required dosage, mixing, make containing Leuconoxine, concentration is respectively 6.0ug/ml, 4.0ug/ml, 3.0ug/ml, 2.0ug/ml, 1.5ug/ml, 1.0ug/ml, the isocyatic slant medium of 0.75ug/ml, 0.5ug/ml.
Be that the H37Rv strain bacteria suspension inoculating loop of 1mg/ml dips ring of numbers by concentration, be inoculated in respectively containing in the culture medium of Leuconoxine series concentration and blank medium slant, be placed in 37 DEG C and cultivate 4 ~ 8 weeks, observation experiment result, result is as shown in table 1.
The experimental example 3 solid medium By Dilution clinical separation of Leuconoxine Ad tuberculosis resistance to ISREMTB strain absolute concentration
The clinical separation of scraping mycobacterium tuberculosis resistance to ISREMTB strain (resistance to isoniazid, streptomycin, rifampicin, the clinical detached dowel of ethambutol mycobacterium tuberculosis) culture from inclined-plane, join in 3mlMiddlebrook7H9 broth bouillon, add a small amount of bead, screw test tube cap, high vibration grinding in vortex oscillator, with standard Maxwell opacity tube (MacFarlandNo.1) than turbid, be namely made into the bacteria suspension of 1mg/ml.
Leuconoxine is made into respectively the stock solution of high concentration with DMSO, by the tween 80 aseptic ultra-pure water dilution stock solution containing 5% to desired concn, the Leuconoxine diluted is joined 4mlMiddlebrook7H11 agar culture medium (this culture medium 121 DEG C of high pressure steam sterilizations 15 minutes, be cooled to 50 ~ 55 DEG C) by required dosage, mixing, make containing Leuconoxine, concentration is respectively 6.0ug/ml, 4.0ug/ml, 3.0ug/ml, 2.0ug/ml, 1.5ug/ml, 1.0ug/ml, the isocyatic slant medium of 0.75ug/ml, 0.5ug/ml.
Be that the clinical separation of the mycobacterium tuberculosis resistance to ISREMTB strain bacteria suspension inoculating loop of 1mg/ml dips ring of numbers by concentration, be inoculated in containing in the culture medium of Leuconoxine series concentration and blank medium slant respectively, be placed in 37 DEG C to cultivate 4 ~ 8 weeks, observation experiment result, result is as shown in table 1.
Table 1 solid medium By Dilution Leuconoxine anti-tubercle bacillus absolute concentration result
Conclusion: Leuconoxine has very strong anti-tubercle bacillus and 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 tubercular drugs.
Claims (4)
- The application of 1.Leuconoxine in anti-tubercle bacillus drugs, described compound L euconoxine structure is as shown in formula I:
- 2. the application of Leuconoxine in anti-tubercle bacillus drugs as claimed in claim 1, is characterized in that mycobacterium tuberculosis strain is mycobacterium tuberculosis type strain H37Rv.
- 3. an anti-tubercle bacillus drugs, it is characterized in that by Leuconoxine described in claim 1 being that active component interpolation adjuvant is prepared from, preparation method, for getting 5 g of compound Leuconoxine, adds 195 grams, dextrin, and mixing, Conventional compression makes 1000.
- 4. an anti-tubercle bacillus drugs, it is characterized in that by Leuconoxine described in claim 1 being that active component adds adjuvant and is prepared from, preparation method, for getting 5 g of compound Leuconoxine, adds starch 195 grams, and mixing, encapsulatedly makes 1000.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510939329.9A CN105412097A (en) | 2015-12-16 | 2015-12-16 | Application of Leuconoxine in preparation of antituberculin drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510939329.9A CN105412097A (en) | 2015-12-16 | 2015-12-16 | Application of Leuconoxine in preparation of antituberculin drug |
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| Publication Number | Publication Date |
|---|---|
| CN105412097A true CN105412097A (en) | 2016-03-23 |
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| CN201510939329.9A Pending CN105412097A (en) | 2015-12-16 | 2015-12-16 | Application of Leuconoxine in preparation of antituberculin drug |
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Application publication date: 20160323 |