CN111789831A - Application of phenelzine in preparation of medicine for resisting mycobacterium abscessus infection - Google Patents
Application of phenelzine in preparation of medicine for resisting mycobacterium abscessus infection Download PDFInfo
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- CN111789831A CN111789831A CN202010877056.0A CN202010877056A CN111789831A CN 111789831 A CN111789831 A CN 111789831A CN 202010877056 A CN202010877056 A CN 202010877056A CN 111789831 A CN111789831 A CN 111789831A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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Abstract
The invention discloses a new application of phenelzine. The new application is the application of the phenelzine or the pharmaceutically acceptable salt thereof in preparing products for resisting mycobacterium abscessus infection. The invention adopts a microplate double dilution method to carry out determination on the activity of phenelzine against mycobacterium abscessus, and the result shows that phenelzine has better antibacterial activity on clinically separated mycobacterium abscessus and is expected to find out new application of phenelzine in treating mycobacterium abscessus infection diseases.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to application of phenelzine in preparation of a medicine for resisting mycobacterium abscessus infection.
Background
Nontuberculous Mycobacteria (NTM) refer to Mycobacteria other than Mycobacterium tuberculosis complex and Mycobacterium leprae. NTM is often present in the natural environment and is an opportunistic pathogen. In recent years, infections caused by NTM have been on a rising trend, and seriously threaten human health. It is reported in the literature that the proportion of NTM isolates in culture positive specimens in our country increased from 4.3% in 1979 to 22.9% in 2010. The pathogenic strains of NTM are various, the NTM of different strains has different sensitivity to drugs, and the treatment scheme aiming at the NTM caused by different strains has larger difference. And the NTM has extremely high drug resistance to anti-tuberculosis drugs, such as common anti-tuberculosis drugs like isoniazid, rifampin, streptomycin and the like, and has different degrees of drug resistance, so that the search for a drug with better NTM treatment effect is very necessary.
Phenelzine is an irreversible and non-selective monoamine oxidase inhibitor and is currently used mainly in the treatment of depression. The mechanism of action is mainly to inhibit the activity of enzyme by forming a drug-enzyme complex with monoamine oxidase so as to interfere the normal metabolism of the substrate and influence the normal biological action of the substrate.
Mycobacterium abscessus, which belongs to rapidly growing non-tuberculous mycobacteria, is one of the main causes of pathological changes of skin, soft tissues and bones. The mycobacterium abscessus has different drug resistance to common antituberculosis drugs, such as rifampicin, isoniazid, streptomycin, ethambutol and the like; the bacterial strain has 60-80% of drug resistance rate to common drugs for treating NTM, such as clarithromycin, and most bacterial strains have drug resistance to various anti-tuberculosis drugs.
Disclosure of Invention
An object of the present invention is to provide a novel use of phenelzine or a pharmaceutically acceptable salt thereof.
The new application of the phenelzine or the pharmaceutically acceptable salt thereof provided by the invention is at least one of the following 1) -7):
1) the application in preparing mycobacterium abscessus bacteriostat;
2) the application in preparing products for inhibiting the activity of mycobacterium abscessus;
3) the application in preparing products for resisting mycobacterium abscessus infection;
4) the application in preparing products for preventing and/or treating diseases caused by mycobacterium abscessus;
5) the application of inhibiting the activity of mycobacterium abscessus;
6) the application in resisting mycobacterium abscessus infection;
7) the application in preventing and/or treating diseases caused by mycobacterium abscessus.
The invention relates to phenelzine, CAS No. 156-51-4. The pharmaceutically acceptable salt of phenelzine can be phenelzine hydrochloride or phenelzine sulfate.
Another object of the present invention is to provide a Mycobacterium abscessus bacteriostatic agent.
The active component of the mycobacterium abscessus bacteriostatic agent provided by the invention is phenelzine or pharmaceutically acceptable salt thereof.
It is yet another object of the present invention to provide a product.
The active ingredient of the product provided by the invention is phenelzine or pharmaceutically acceptable salt thereof;
the product has at least one of the following effects:
a) inhibiting mycobacterium abscessus activity;
b) against mycobacterial abscesses;
c) preventing and/or treating diseases caused by mycobacterium abscesses.
In the present invention, the mycobacterium abscessus may be a standard strain of mycobacterium abscessus or a clinical isolate of mycobacterium abscessus or a mycobacterium abscessus carried by a patient infected with mycobacterium abscessus.
In one embodiment of the present invention, the mycobacterium abscessus is mycobacterium abscessus standard strain ATCC 19977.
In another embodiment of the invention, the mycobacterium abscessus is a clinical isolate of mycobacterium abscessus.
The product of the invention can be specifically a medicine.
When necessary, one or more pharmaceutically acceptable carriers can be added into the medicine; the carrier includes diluent, excipient, filler, binder, wetting agent, disintegrating agent, absorption enhancer, surfactant, adsorption carrier, lubricant, etc. which are conventional in the pharmaceutical field.
The above medicine can be made into various forms such as injection, tablet, powder, granule, capsule, oral liquid, paste, cream, etc.; the medicaments in various dosage forms can be prepared according to the conventional method in the pharmaceutical field.
The above medicine can be introduced into body such as muscle, intradermal, subcutaneous, intravenous, and mucosal tissue by injection, spray, nasal drop, eye drop, penetration, absorption, physical or chemical mediated method; or mixed or coated with other materials and introduced into body.
The invention also provides a method for inhibiting the activity of mycobacterium abscessus.
The method for inhibiting the activity of mycobacterium abscessus comprises the following steps: a substance containing phenelzine or a pharmaceutically acceptable salt thereof as an active ingredient is used for inhibiting the activity of Mycobacterium abscessus.
Wherein, the mycobacterium abscessus can be a mycobacterium abscessus standard strain or a mycobacterium abscessus clinical isolate.
In the above method, the mycobacterium abscessus may be a standard strain of mycobacterium abscessus or a clinical isolate of mycobacterium abscessus.
The lowest using concentration of the phenelzine or the pharmaceutically acceptable salt thereof in the substance taking the phenelzine or the pharmaceutically acceptable salt thereof as the active ingredient is not lower than the Minimum Inhibitory Concentration (MIC) of the mycobacterium abscessus inhibited by the substance.
The method is a non-disease diagnostic treatment method. For example, as a positive control in screening for drugs sensitive to M.abscessus.
The invention adopts a microplate double dilution method to carry out the activity determination of the phenelzine on the mycobacterium abscessus, and the result shows that the phenelzine has better antibacterial activity on standard strains of the mycobacterium abscessus and clinically separated mycobacterium abscessus, and is expected to develop the new application of the phenelzine in the treatment of the mycobacterium abscessus infection diseases.
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FIG. 1 is a graph of MIC concentration profile of phenelzine against clinically isolated Mycobacterium abscessus strains.
Detailed Description
The present invention will be further illustrated with reference to the following specific examples, but the present invention is not limited to the following examples. The experimental procedures in the following examples are conventional unless otherwise specified. The test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified. The quantitative tests in the following examples, all set up three replicates and the results averaged.
Phenylethylhydrazine sulfate (CAS: 156-51-4): purchased from Sigma, cat #: p6777;
the molecular formula is as follows: c8H12N2·H2SO4The structural formula is as follows:
standard strain of mycobacterium abscessus: ATCC 19977.
Example 1 detection of bacteriostatic activity of phenelzine against Mycobacterium abscessus Standard Strain
The drug to be tested: phenylethylhydrazine sulfate
1. Add 100. mu.l Mueller Hinton (MH) medium to each well of a 96-well plate;
2. after the step 1 is completed, taking the 96-well plate, adding 100 mu l of a drug solution to be detected (prepared by DMSO) with the concentration of 6400 mu g/mL into the 12 th row, sucking 100 mu l after mixing uniformly, adding into the 11 th row, sequentially diluting in a gradient manner to the 2 nd row, sucking 100 mu l and discarding, wherein the 1 st row contains no drug and is a positive control well. 3 multiple wells were set for each concentration.
3. After the step 2 is completed, taking the 96-well plate, adding 100 mu l of mycobacterium abscessus standard strain bacterial suspension into each well, so that the final volume of each well is 200 mu l, and the final concentration of the bacterial liquid is 2.5 multiplied by 105CFU/mL; the final drug concentration in each well is detailed in table 1.
The preparation method of the mycobacterium abscessus standard strain bacterial suspension comprises the following steps: inoculating mycobacterium abscessus standard strain into neutral Roche medium, culturing in 37 deg.C incubator for 1 week, scraping the strain in growth log phase on neutral Roche medium, grinding, and diluting with Mueller Hinton (MH) medium.
TABLE 1 Final drug concentration in each well column
4. After completion of step 3, the 96-well plate was placed in a 37 ℃ incubator and cultured for 3 days.
5. After completion of step 4, the 96-well plate was taken, and 20. mu.l of Alamar blue and 50. mu.l of 5% Tween80 were added to each well, followed by further incubation in an incubator at 37 ℃ for 24 hours.
6. After step 5, the 96-well plate was taken, the Minimum Inhibitory Concentration (MIC) was read, and the inhibition rate was calculated.
Minimum Inhibitory Concentration (MIC) reading method: the Minimum Inhibitory Concentration (MIC) is the concentration of drug that can inhibit the growth of 90% of colonies. Minimum drug concentration that inhibits > 90% production of reduced Alamar blue by fluorescence detection (Ex/Em,530nm/600 nm).
Inhibition rate%.
The background fluorescence value is the fluorescence value of the negative control, and the fluorescence value of the growth control hole is the fluorescence value of the positive control.
The negative control is a culture medium without the addition of medicines and bacteria liquid, and the positive control is a bacteria-containing culture medium without the addition of medicines.
The results showed that the MIC of phenelzine to Mycobacterium abscessus standard strain ATCC19977 was 100. mu.g/mL.
Example 2 detection of bacteriostatic activity of Phenylethylhydrazine on clinically isolated Mycobacterium abscessus strains
Clinically isolating the strain: 23 strains are separated and cultured from sputum specimens of patients infected by mycobacterium abscesses, and are identified as mycobacterium abscesses by sequencing in regions among 16SrRNA, hsp65, rpoB and 16-23S rRNA.
The drug to be tested: phenylethylhydrazine sulfate
The bacteriostatic activity of the test drug against 23 clinically isolated mycobacterium abscessus strains was tested as in example 1.
The MIC results are shown in table 2. The MIC concentration profile statistics are shown in table 3 and figure 1.
TABLE 2 MIC of phenelzine for clinical isolation of Mycobacterium abscessus strains
TABLE 3 MIC concentration distribution statistics of phenelzine for clinically isolated Mycobacterium abscessus strains
The result shows that the phenelzine has better antibacterial activity on clinically separated mycobacterium abscessus, and is expected to develop new application of the phenelzine in treating mycobacterium abscessus infection diseases.
The present invention has been described in detail above. It will be apparent to those skilled in the art that the invention can be practiced in a wide range of equivalent parameters, concentrations, and conditions without departing from the spirit and scope of the invention and without undue experimentation. While the invention has been described with reference to specific embodiments, it will be appreciated that the invention can be further modified. In general, this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains. The use of some of the essential features is possible within the scope of the claims attached below.
Claims (10)
1. Use of phenelzine or a pharmaceutically acceptable salt thereof in at least one of:
1) the application in preparing mycobacterium abscessus bacteriostat;
2) the application in preparing products for inhibiting the activity of mycobacterium abscessus;
3) the application in preparing products for resisting mycobacterium abscessus infection;
4) the application in preparing products for preventing and/or treating diseases caused by mycobacterium abscessus.
2. Use of phenelzine or a pharmaceutically acceptable salt thereof in at least one of:
5) the application of inhibiting the activity of mycobacterium abscessus;
6) the application in resisting mycobacterium abscessus infection;
7) the application in preventing and/or treating diseases caused by mycobacterium abscessus.
3. Use according to claim 1 or 2, characterized in that: the mycobacterium abscessus is a mycobacterium abscessus standard strain, or a mycobacterium abscessus clinical isolate, or mycobacterium abscessus carried by a patient infected by mycobacterium abscessus;
the product is a medicine.
4. A mycobacterium abscessus bacteriostatic agent contains phenelzine or its pharmaceutically acceptable salt as active ingredient.
5. The bacteriostatic agent according to claim 4, wherein: the mycobacterium abscessus is a mycobacterium abscessus standard strain, or a mycobacterium abscessus clinical isolate, or mycobacterium abscessus carried by a patient infected by mycobacterium abscessus.
6. A product contains phenelzine or its pharmaceutically acceptable salt as active ingredient;
the product has at least one of the following effects:
a) inhibiting mycobacterium abscessus activity;
b) against mycobacterial abscesses;
c) preventing and/or treating diseases caused by mycobacterium abscesses.
7. The product of claim 6, wherein: the mycobacterium abscessus is a mycobacterium abscessus standard strain, or a mycobacterium abscessus clinical isolate, or mycobacterium abscessus carried by a patient infected by mycobacterium abscessus.
8. The product according to claim 6 or 7, characterized in that: the product is a medicine.
9. A method of inhibiting mycobacterium abscessus activity, comprising the steps of: a substance containing phenelzine or a pharmaceutically acceptable salt thereof as an active ingredient is used for inhibiting the activity of Mycobacterium abscessus.
10. The method of claim 9, wherein: the mycobacterium abscessus is a mycobacterium abscessus standard strain or a mycobacterium abscessus clinical isolate.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112386588A (en) * | 2020-11-17 | 2021-02-23 | 首都医科大学附属北京胸科医院 | Application of phenelzine in preparation of drugs for resisting mycobacterium avium infection |
| CN114469914A (en) * | 2020-11-13 | 2022-05-13 | 山东大学 | Application of Phenlzine in preparation of coronavirus papain-like protease inhibitor and coronavirus infection resisting medicine |
| CN116808035A (en) * | 2023-08-25 | 2023-09-29 | 深圳市第三人民医院(深圳市肝病研究所) | 199596-05-9 application as antitubercular compound |
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| CN110960521A (en) * | 2019-12-20 | 2020-04-07 | 首都医科大学附属北京胸科医院 | Application of carbonyl cyanide3-chlorophenylhydrazone in preparation of antibacterial agent for mycobacterium abscessus |
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| CN110960521A (en) * | 2019-12-20 | 2020-04-07 | 首都医科大学附属北京胸科医院 | Application of carbonyl cyanide3-chlorophenylhydrazone in preparation of antibacterial agent for mycobacterium abscessus |
| CN111096969A (en) * | 2020-01-17 | 2020-05-05 | 首都医科大学附属北京胸科医院 | Use of sutezolid (PNU-100480) in infection of M.avium complex |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114469914A (en) * | 2020-11-13 | 2022-05-13 | 山东大学 | Application of Phenlzine in preparation of coronavirus papain-like protease inhibitor and coronavirus infection resisting medicine |
| CN112386588A (en) * | 2020-11-17 | 2021-02-23 | 首都医科大学附属北京胸科医院 | Application of phenelzine in preparation of drugs for resisting mycobacterium avium infection |
| CN116808035A (en) * | 2023-08-25 | 2023-09-29 | 深圳市第三人民医院(深圳市肝病研究所) | 199596-05-9 application as antitubercular compound |
| CN116808035B (en) * | 2023-08-25 | 2023-10-31 | 深圳市第三人民医院(深圳市肝病研究所) | 199596-05-9 application as antitubercular compound |
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