CN106265635A - Linderolide H application in preparation treatment anti-tubercle bacillus drugs - Google Patents
Linderolide H application in preparation treatment anti-tubercle bacillus drugs Download PDFInfo
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- CN106265635A CN106265635A CN201610803364.2A CN201610803364A CN106265635A CN 106265635 A CN106265635 A CN 106265635A CN 201610803364 A CN201610803364 A CN 201610803364A CN 106265635 A CN106265635 A CN 106265635A
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- linderolide
- tubercle bacillus
- tuberculosis
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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Abstract
The invention discloses Linderolide H application in preparing anti-tubercle bacillus drugs.The present invention is directed to that current incidence of tuberculosis is high, the appearance of tubercule bacillus multiple antibiotic resistant strain, make incidence of tuberculosis and mortality rate present situation in rising trend, find that Linderolide H has the activity significantly inhibiting tulase, there is good application prospect.The Linderolide H that the present invention relates to purposes in preparation treatment anti-tubercle bacillus drugs belongs to first public, owing to framework types belongs to brand-new framework types, and it is unexpectedly strong for tulase inhibitory activity, there is not the possibility being provided any enlightenment by other compounds, possessing prominent substantive distinguishing features, the preventing and treating being simultaneously used for tubercle bacillus affection obviously has the most progressive.
Description
Technical field
The present invention relates to the new application of compound L inderolide H, particularly relate to Linderolide H in preparation treatment
Application in anti-tubercle bacillus drugs.
Background technology
The most global morbidity lungy, in increasing trend, is estimated according to World Health Organization (WHO) (WHO), and the whole world is tied at present
The population that core mycobacteria (Mycobacterium tuberculosis, MTB) infects accounts for 1/3rd of world population, wherein
5～10% the infected become tuberculosis patient.China occurs active tuberculosis patient 1,300,000 example, wherein infectiousness every year
Pulmonary tuberculosis about 600,000 example, wherein infectiousness pulmonary tuberculosis about 600,000 example, be one of whole world tuberculosis high burden country.
Come out one after another from antituberculotics, make treatment lungy play epoch-making change.Yet with tuberculosis sufferer
The Case management of person the most not ten sectional specification, irregular chemotherapy, abuse antituberculotics, make drug resistance of tuberculosis situation day by day serious,
And the change of drug resistance tends to multi-medicament drug resistance simultaneously, this causes extreme difficulties to preventing and controlling lungy.Therefore
Finding new antituberculotics, the antituberculotics of the most anti-multidrug resistance, to protection people's health, has important
Meaning.
The compound L inderolide H that the present invention relates to be one within 2013, deliver (Qing Liu, et al.,
Sesquiterpene lactones from the roots of Lindera strychnifolia.Phytochemistry,
87 (2013) 112 118.) noval chemical compound, this compound has brand-new framework types, and current purposes merely relates to suppression
Function of tumor (Qing Liu, et al., Sesquiterpene lactones from the roots of Lindera
Strychnifolia.Phytochemistry, 87 (2013) 112 118.), for the Linderolide H that the present invention relates to
Purposes in preparation treatment anti-tubercle bacillus drugs belongs to first public, owing to belonging to brand-new structure type, and its for
The activity of anti-tubercle bacillus is unexpectedly strong, and there is not the possibility being provided any enlightenment by other compounds, possesses prominent reality
Matter feature, is simultaneously used for anti-tubercle bacillus and obviously has the most progressive.
Summary of the invention
Do not find in it is an object of the invention to study according to existing Linderolide H that it has anti-anti-tubercle bacillus activity
The present situation of report, it is provided that Linderolide H application in preparing anti-anti-tubercle bacillus drugs.
Described compound L inderolide H structure is as shown in formula I:
Inventor first does examination bacterial strain with bacillus calmette-guerin vaccine, uses disk diffusion method to live the anti-tubercle bacillus of Linderolide H
Property carries out preliminary test, and according to the result of preliminary test, the present invention determines this compound pair with solid medium dilution method again
Bacillus calmette-guerin vaccine, mycobacterium tuberculosis type strain H37Rv strain and the minimum of substance of medicines-resistant branched tubercle bacillus (MDR MTB) three kinds of tulases
Mlc, experimental result confirms that Linderolide H has the strongest anti-tubercle bacillus and anti-drug resistance tulase activity, can make
For treating the lead compound of tubercle bacillus affection disease it can also be used to tubercular drugs is treated in preparation.
Compared with prior art, there is advantages that
1. the invention provides a kind of Linderolide H that can be used for antituberculosis treatment, thus expand tuberculosis
The kind of bacterium medicine；
2., tubercule bacillus multiple antibiotic resistant strain high for current incidence of tuberculosis and the dual sense of HIV (human immunodeficiency virus)
The appearance of dye, makes incidence of tuberculosis and mortality rate present situation in rising trend, present invention discover that Linderolide H has anti-
Tulase and the feature of drug resistant M bacterium activity, can be used for the preparation of antituberculotics, have boundless application prospect；
3. the Linderolide H that the present invention relates to purposes in preparation treatment anti-tubercle bacillus drugs belongs to public first
Opening, owing to framework types belongs to brand-new framework types, and it is unexpectedly strong for tulase inhibitory activity, does not exists
Provided the possibility of any enlightenment by other compounds, possess prominent substantive distinguishing features, be simultaneously used for the preventing and treating of tubercle bacillus affection
Obviously have the most progressive.
Detailed description of the invention
The preparation method of compound L inderolide H involved in the present invention see document (Qing Liu, et al.,
Sesquiterpene lactones from the roots of Lindera strychnifolia.Phytochemistry,
87(2013)112–118.)
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by concrete real
Execute any restriction of example, but be defined in the claims.
Embodiment 1: the preparation of compound L inderolide H tablet involved in the present invention:
Taking 20 g of compound Linderolide H, the customary adjuvant 180 grams of tablet is prepared in addition, mixing, conventional tablet presses
Make 1000.
Embodiment 2: the preparation of compound L inderolide H capsule involved in the present invention:
Taking 20 g of compound Linderolide H, the customary adjuvant such as starch 180 grams of capsule is prepared in addition, mixing, dress
Capsule makes 1000.
Experimental example 1 solid medium dilution method measures Linderolide H anti-bacillus calmette-guerin vaccine (BCG) absolute concentration
From inclined-plane, scrape BCG cultures, join in 3ml Middlebrook7H9 broth bouillon, add few
Amount bead, screws test tube cap, and in vortex oscillator, high vibration grinds, with standard Maxwell opacity tube
(MacFarlandNo.1) ratio is turbid, is i.e. made into bacillus calmette-guerin vaccine (BCG) bacteria suspension of 1mg/ml.
Linderolide H DMSO is made into the stock solution of high concentration, dilutes with the aseptic ultra-pure water of tween 80 containing 5%
The Linderolide H diluted, to desired concn, is joined 4ml Middlebrook7H11 agar by required dosage by stock solution
Culture medium (this culture medium 121 DEG C of high pressure steam sterilizations 15 minutes, be cooled to 50～55 DEG C), mixing, make and contain
Linderolide H, concentration is respectively 6.0ug/ml, 4.0ug/ml, 3.0ug/ml, 2.0ug/ml, 1.5ug/ml, 1.0ug/
The isocyatic slant medium of ml, 0.75ug/ml, 0.5ug/ml.
Bacillus calmette-guerin vaccine (BCG) the bacteria suspension inoculating loop that concentration is 1mg/ml is dipped ring of numbers, is inoculated in respectively and contains
In the culture medium of Linderolide H series concentration and blank medium slant, it is placed in 37 DEG C and cultivates 4～8 weeks, observe real
Testing result, result is as shown in table 1.
In the present embodiment, Middlebrook7H9 broth bouillon used and Middlebrook7H11 agar culture medium are this
Skilled person carries out conventional culture medium when tulase is cultivated, and its formula uses conventional formulation.
It is exhausted that experimental example 2 solid medium dilution method measures Linderolide H Killing Mycobacterium Tuberculosis type strain H37Rv strain
To concentration
From inclined-plane, scrape mycobacterium tuberculosis type strain H37Rv strain culture, join 3ml Middlebrook7H9
In broth bouillon, adding a small amount of bead, screw test tube cap, in vortex oscillator, high vibration grinds, with standard Maxwell
Opacity tube (MacFarland No.1) ratio is turbid, is i.e. made into the H37Rv strain bacteria suspension of 1mg/ml.
Linderolide H is made into DMSO respectively the stock solution of high concentration, with containing 5% the aseptic ultra-pure water of tween 80
The Linderolide H diluted, to desired concn, is joined 4ml Middlebrook7H11 by required dosage by dilution stock solution
Agar culture medium (this culture medium 121 DEG C of high pressure steam sterilizations 15 minutes, be cooled to 50～55 DEG C), mixing, make and contain
Linderolide H, concentration is respectively 6.0ug/ml, 4.0ug/ml, 3.0ug/ml, 2.0ug/ml, 1.5ug/ml, 1.0ug/
The isocyatic slant medium of ml, 0.75ug/ml, 0.5ug/ml.
The H37Rv strain bacteria suspension inoculating loop that concentration is 1mg/ml is dipped ring of numbers, is inoculated in containing Linderolide respectively
In the culture medium of H series concentration and blank medium slant, it is placed in 37 DEG C and cultivates 4～8 weeks, observation experiment result, result
As shown in table 1.
Experimental example 3 solid medium dilution method measures Linderolide H Ad tuberculosis and is clinically separated resistance to ISRE
MTB strain absolute concentration
From inclined-plane scrape mycobacterium tuberculosis be clinically separated the MTB of resistance to ISRE strain (resistance to isoniazid, streptomycin, rifampicin,
Ethambutol mycobacterium tuberculosis is clinically separated post) culture, join in 3ml Middlebrook7H9 broth bouillon, add
Entering a small amount of bead, screw test tube cap, in vortex oscillator, high vibration grinds, with standard Maxwell opacity tube
(MacFarland No.1) ratio is turbid, is i.e. made into the bacteria suspension of 1mg/ml.
Linderolide H is made into DMSO respectively the stock solution of high concentration, with containing 5% the aseptic ultra-pure water of tween 80
The Linderolide H diluted, to desired concn, is joined 4ml Middlebrook7H11 by required dosage by dilution stock solution
Agar culture medium (this culture medium 121 DEG C of high pressure steam sterilizations 15 minutes, be cooled to 50～55 DEG C), mixing, make and contain
Linderolide H, concentration is respectively 6.0ug/ml, 4.0ug/ml, 3.0ug/ml, 2.0ug/ml, 1.5ug/ml, 1.0ug/
The isocyatic slant medium of ml, 0.75ug/ml, 0.5ug/ml.
The mycobacterium tuberculosis that concentration is 1mg/ml is clinically separated the MTB of resistance to ISRE strain bacteria suspension inoculating loop and dips number
Ring, is inoculated in the culture medium containing Linderolide H series concentration and blank medium slant respectively, is placed in 37 DEG C of trainings
Supporting 4～8 weeks, observation experiment result, result is as shown in table 1.
Table 1 solid medium dilution method measures Linderolide H anti-tubercle bacillus absolute concentration result
Conclusion: Linderolide H has the strongest anti-tubercle bacillus and anti-drug resistance tulase activity, can be as treatment knot
The lead compound of solani infection disease is it can also be used to tubercular drugs is treated in preparation.
Claims (1)
1.Linderolide H application in anti-tubercle bacillus drugs, described compound L inderolide H structure such as formula I
Shown in:
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610803364.2A CN106265635A (en) | 2016-09-05 | 2016-09-05 | Linderolide H application in preparation treatment anti-tubercle bacillus drugs |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610803364.2A CN106265635A (en) | 2016-09-05 | 2016-09-05 | Linderolide H application in preparation treatment anti-tubercle bacillus drugs |
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| CN201610803364.2A Pending CN106265635A (en) | 2016-09-05 | 2016-09-05 | Linderolide H application in preparation treatment anti-tubercle bacillus drugs |
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- 2016-09-05 CN CN201610803364.2A patent/CN106265635A/en active Pending
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Application publication date: 20170104 |