阅读说明：本技术 苯乙肼在制备抗脓肿分枝杆菌感染的药物中的应用 (Application of phenelzine in preparation of medicine for resisting mycobacterium abscessus infection ) 是由 黄海荣 王桂荣 孙晴 姜广路 于霞 陈素婷 于 2020-08-27 设计创作，主要内容包括：本发明公开了苯乙肼的新用途。该新用途是苯乙肼或其药学上可接受的盐在制备抗脓肿分枝杆菌感染的产品中的应用。本发明采用微孔板二倍稀释法进行苯乙肼抗脓肿分枝杆菌活性进行测定,结果表明,苯乙肼对临床分离的脓肿分枝杆菌有较好的抑菌活性,有望发掘出苯乙肼在治疗脓肿分枝杆菌感染疾病中的新用途。(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.)

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.

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.

Drawings

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.