阅读说明：本技术 苯乙肼在制备抗偶发分枝杆菌感染的药物中的应用 (Application of phenelzine in preparation of drug for resisting mycobacterium fortuitum 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偶发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偶发分枝杆菌活性进行测定,结果表明,苯乙肼对临床分离的偶发分枝杆菌有较好的抑菌活性,有望发掘出苯乙肼在治疗偶发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 phenelzine or pharmaceutically acceptable salts thereof in preparing products for resisting mycobacterium fortuitum infection. The invention adopts a microplate double dilution method to carry out the determination of the activity of the phenelzine against mycobacterium fortuitum, and the result shows that the phenelzine has better bacteriostatic activity on clinically separated mycobacterium fortuitum and is expected to develop the new application of the phenelzine in the treatment of mycobacterium fortuitum infection diseases.)

1. Use of phenelzine or a pharmaceutically acceptable salt thereof in at least one of:

1) the application in the preparation of mycobacterium fortuitum bacteriostat;

2) the application in preparing products for inhibiting the activity of mycobacterium fortuitum;

3) the application in preparing products for resisting mycobacterium fortuitum infection;

4) the application in preparing products for preventing and/or treating diseases caused by mycobacterium fortuitum.

2. Use of phenelzine or a pharmaceutically acceptable salt thereof in at least one of:

5) the application in inhibiting the activity of mycobacterium fortuitum;

6) use against mycobacterium fortuitum infection;

7) the application in preventing and/or treating diseases caused by mycobacterium fortuitum.

3. Use according to claim 1 or 2, characterized in that: the mycobacterium fortuitum is a standard strain of mycobacterium fortuitum, or a clinical isolate of mycobacterium fortuitum, or mycobacterium fortuitum carried by a patient infected by mycobacterium fortuitum;

the product is a medicine.

4. A bacteriostatic agent for Mycobacterium fortuitum contains phenelzine or its pharmaceutically acceptable salt as active ingredient.

5. The bacteriostatic agent according to claim 4, wherein: the mycobacterium fortuitum is a standard strain of mycobacterium fortuitum, or a clinical isolate of mycobacterium fortuitum, or mycobacterium fortuitum carried by a patient infected by mycobacterium fortuitum.

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 fortuitum activity;

b) against mycobacterium fortuitum infection;

c) preventing and/or treating diseases caused by mycobacterium fortuitum.

7. The product of claim 6, wherein: the mycobacterium fortuitum is a standard strain of mycobacterium fortuitum, or a clinical isolate of mycobacterium fortuitum, or mycobacterium fortuitum carried by a patient infected by mycobacterium fortuitum.

8. The product according to claim 6 or 7, characterized in that: the product is a medicine.

9. A method of inhibiting the activity of mycobacterium fortuitum comprising the steps of: use of a substance containing phenelzine or a pharmaceutically acceptable salt thereof as an active ingredient for inhibiting the activity of Mycobacterium fortuitum.

10. The method of claim 9, wherein: the mycobacterium fortuitum is a mycobacterium fortuitum standard strain or a mycobacterium fortuitum 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 fortuitum 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 fortuitum, belonging to rapidly growing nontuberculous mycobacteria, often causes lesions of skin, soft tissues and bones. In recent years, the drug resistance degree of mycobacterium fortuitum to anti-tuberculosis drugs in China is continuously increased, and the drug resistance rate of the mycobacterium fortuitum to common anti-tuberculosis drugs such as rifampicin, isoniazid, streptomycin, ethambutol and the like is up to more than 70%; the strain also has drug resistance to common drugs for treating NTM, such as clarithromycin, and most strains have drug resistance to various antituberculosis drugs simultaneously.

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 the preparation of mycobacterium fortuitum bacteriostat;

2) the application in preparing products for inhibiting the activity of mycobacterium fortuitum;

3) the application in preparing products for resisting mycobacterium fortuitum infection;

4) the application in the preparation of products for preventing and/or treating diseases caused by mycobacterium fortuitum;

5) the application in inhibiting the activity of mycobacterium fortuitum;

6) use against mycobacterium fortuitum infection;

7) the application in preventing and/or treating diseases caused by mycobacterium fortuitum.

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 fortuitum bacteriostatic agent.

The active component of the mycobacterium fortuitum 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 fortuitum activity;

b) against mycobacterium fortuitum infection;

c) preventing and/or treating diseases caused by mycobacterium fortuitum.

In the present invention, the mycobacterium fortuitum may be a standard strain of mycobacterium fortuitum or a clinical isolate of mycobacterium fortuitum or a mycobacterium fortuitum carried by a patient infected with mycobacterium fortuitum.

In one embodiment of the present invention, the Mycobacterium fortuitum is Mycobacterium fortuitum Standard strain ATCC 6841.

In another embodiment of the present invention, the Mycobacterium fortuitum is a clinical isolate of Mycobacterium fortuitum.

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 fortuitum.

The method for inhibiting the activity of the mycobacterium fortuitum comprises the following steps: use of a substance containing phenelzine or a pharmaceutically acceptable salt thereof as an active ingredient for inhibiting the activity of Mycobacterium fortuitum.

Wherein, the mycobacterium fortuitum can be a standard strain of mycobacterium fortuitum or a clinical isolate of mycobacterium fortuitum.

In the above method, the Mycobacterium fortuitum may be a standard strain of Mycobacterium fortuitum or a clinical isolate of Mycobacterium fortuitum.

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 fortuitum inhibited by the phenelzine or the pharmaceutically acceptable salt thereof.

The method is a non-disease diagnostic treatment method. For example, as a positive control in screening for drugs sensitive to Mycobacterium fortuitum.

The invention uses a microplate double dilution method to carry out the phenyl ethyl hydrazine activity determination of resisting accidental mycobacteria, and the result shows that the phenyl ethyl hydrazine has better bacteriostatic activity to the standard strains of the accidental mycobacteria and clinical isolated accidental mycobacteria, and is expected to find out the new application of the phenyl ethyl hydrazine in treating the accidental mycobacteria infection diseases.

Drawings

FIG. 1 is a graph showing MIC concentration profiles of phenelzine against clinically isolated Mycobacterium fortuitum 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 fortuitum: ATCC 6841.