CN112870166B - Nuclear plexus penicillin solid dispersion, preparation method and application - Google Patents
Nuclear plexus penicillin solid dispersion, preparation method and application Download PDFInfo
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- CN112870166B CN112870166B CN202110072837.7A CN202110072837A CN112870166B CN 112870166 B CN112870166 B CN 112870166B CN 202110072837 A CN202110072837 A CN 202110072837A CN 112870166 B CN112870166 B CN 112870166B
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- penicillin
- solid dispersion
- pvp
- pleurotus citrinopileatus
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61P31/06—Antibacterial agents for tuberculosis
Abstract
The invention discloses a Pleurotus citrinopileatus solid dispersion, a preparation method and application thereof, comprising mixing Pleurotus citrinopileatus and PVP-k30 according to the proportion, wherein the mass ratio of the Pleurotus citrinopileatus to PVP-k30 can be 1:4, 1:6 or 1: 8. The invention has the advantages that the application of the existing Pleurotus citrinopileatus in the field of medicine is limited due to poor water solubility and poor oral absorption of the existing Pleurotus citrinopileatus, and the invention firstly solves the difficulties of poor water solubility and poor oral absorption of the Pleurotus citrinopileatus; experiments prove that the invention can detect the highest peak of the obvious blood concentration after the rat is orally taken for 4 hours, and the raw material of the tubercle penicillin is orally taken, so that the peak of the blood concentration can not be detected, and the invention lays a foundation for creating a novel anti-tuberculosis medicament with high efficiency and low toxicity.
Description
Technical Field
The invention relates to the field of medical drugs, and in particular relates to a solid dispersion of nucleopolypenicillin, a preparation method and application thereof.
Background
Tuberculosis is a killer of the first infectious disease of the world, millions of people die of tuberculosis every year, and the country is one of 30 countries with serious prevalence of multi-drug resistant tuberculosis in the world and occupies the third country with high tuberculosis burden in the world. Since various traditional medicines such as isoniazid, rifampicin and the like appeared in the 60 th century, multi-drug resistant strains of tubercle bacillus continuously appear due to the existence of irregular treatment, abuse of antitubercular drugs and the like, and great difficulty is caused to the prevention and treatment work of tuberculosis. The new drugs sirtui and Deltyba were not available until 2012 for the treatment of drug-resistant tubercle bacillus. However, the two drugs also have great side effects, so that the research and development of novel efficient and low-toxicity antituberculosis drugs have important significance for effectively suppressing tuberculosis circulation and improving the tuberculosis prevention and treatment effect.
Tuberculosis is a serious infectious disease to be urgently controlled and treated in China and even all over the world, and the new effective medicament not only has good market prospect, but also has great social significance. Serine/threonine protein kinase G (PknG) is an effector protein secreted by Mycobacterium tuberculosis into host cells, is a virulence factor necessary for the Mycobacterium tuberculosis to infect the host cells, plays an important role in regulating the growth, drug resistance and survival of bacteria in the host cells, and PknG becomes a new target for screening antitubercular drugs. In earlier work, the research team constructs a screening model of an antituberculosis drug targeting PknG, and screens a lead compound, namely the tuberculin (Sclerotirin), with the inhibitory activity on PknG higher than that of the existing homotarget compound from a secondary metabolite library of marine microorganisms, wherein IC50 of the lead compound is 76.50 +/-3.87 mu M. The sclerotropin can effectively eliminate the macrophages and the mycobacteria in mice independently or in combination with rifampicin, has no cytotoxicity and animal acute toxicity, and has clinical application potential for tuberculosis treatment. However, due to poor water solubility and poor oral absorption of Sclerotiorin, the application of Sclerotiorin in the field of medicine is limited.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a solid dispersion of the ribbonicin, a preparation method and application thereof, the method overcomes the difficulties of poor water solubility and poor oral absorption of the ribbonicin, and the solid dispersion of the ribbonicin is prepared, and the prepared solid dispersion can improve the water solubility and the oral absorption of the compound.
In order to achieve the purpose, the invention adopts the following technical scheme:
a Plexin solid dispersion, comprising Plexin and PVP-k30 mixed in a ratio, wherein the mass ratio of Plexin to PVP-k30 can be 1:4, 1:6 or 1: 8.
The invention also provides a preparation method of the nucleopolypenicillin solid dispersion, which comprises the following steps:
s1, weighing the nucleoprotein penicillin and PVP-k30 in proportion;
s2, adding ethanol to dissolve the nucleoprotein and PVP-k30 to form a mixed solution;
s3 stirring the mixture vigorously until it is clear;
s4, placing the clear mixed solution obtained in the step S3 in a rotary evaporator to remove ethanol;
s5, after freezing and solidifying, placing the mixture into a vacuum drying box for vacuum drying;
s6, the dried mixture is crushed to obtain the solid dispersion of the penicillin.
Preferably, the mass ratio of the Plexin to the PVP-k30 may be 1:4, 1:6 or 1: 8.
The preferred operating temperature of the rotary evaporator is 65 ℃.
Preferably, the temperature of the vacuum drying is 40 ℃, and the drying time is 24 hours.
Aiming at the prepared nucleoplasm penicillin solid dispersion, the invention provides a medicine application for treating tuberculosis.
Preferably, the mass ratio of the nucleoplasm penicillin to the PVP-k30 in the application is 1: 6.
The invention has the advantages that the application of the existing Pleurotus citrinopileatus in the field of medicine is limited due to poor water solubility and poor oral absorption of the existing Pleurotus citrinopileatus, and the invention firstly solves the difficulties of poor water solubility and poor oral absorption of the Pleurotus citrinopileatus; experiments prove that the invention can detect the highest peak of the obvious blood concentration after the rat is orally taken for 4 hours, and the raw material of the tubercle penicillin is orally taken, so that the peak of the blood concentration can not be detected, and the invention lays a foundation for creating a novel anti-tuberculosis medicament with high efficiency and low toxicity.
Detailed Description
The present invention will be further described below, and the preferred embodiment is based on the technical scheme, and the detailed implementation manner and the specific operation process are given, but the protection scope of the present invention is not limited to the embodiment.
The invention relates to a Plexin solid dispersion, which comprises Plexin and PVP-k30 mixed according to the proportion, wherein the mass ratio of the Plexin to PVP-k30 can be 1:4, 1:6 or 1: 8.
The invention also provides a preparation method of the nucleopolypenicillin solid dispersion, which comprises the following steps:
s1, weighing the nucleoprotein penicillin and PVP-k30 in proportion;
s2, adding ethanol to dissolve the nucleoprotein and PVP-k30 to form a mixed solution;
s3 stirring the mixture vigorously until it is clear;
s4, placing the clear mixed solution obtained in the step S3 in a rotary evaporator to remove ethanol;
s5, after freezing and solidifying, placing the mixture into a vacuum drying box for vacuum drying;
s6, the dried mixture is crushed to obtain the solid dispersion of the penicillin.
Preferably, the mass ratio of the Plexin to the PVP-k30 may be 1:4, 1:6 or 1: 8.
The preferred operating temperature of the rotary evaporator is 65 ℃.
Preferably, the temperature of the vacuum drying is 40 ℃, and the drying time is 24 hours.
Aiming at the prepared nucleoplasm penicillin solid dispersion, the invention provides a medicine application for treating tuberculosis.
Preferably, the mass ratio of the nucleoplasm penicillin to the PVP-k30 in the application is 1: 6.
Example 1
The solid dispersion of penicillin of the present invention is as previously described and is determined by the solid dispersion solubility measurement comprising:
1. determination of the absorption wavelength
Weighing appropriate amount of the nucleoprotein and PEG6000, preparing a solution with appropriate concentration by using distilled water (represented by the solution A) containing 10% ethanol (V/V), and scanning within the range of 200-600 nm by using the solution as a blank control to determine the measurement wavelength of the nucleoprotein and the interference of the PEG6000 at the wavelength.
2. Standard curve
Precisely weighing 0.8mg of the Plexin, placing the weighed materials into a 10ml volumetric flask, adding ethanol to dissolve the materials and diluting the materials to a scale, thus obtaining a stock solution of 1mmol/L, and precisely diluting the stock solution to 1/40, 1/20, 1/12, 1/8 and 1/6mmol/L by using the solution A. And measuring the absorbance at 278nm according to a spectrophotometric method, and obtaining a unitary linear regression equation of the molar concentration and the absorbance of the penicillin by regression.
3. Solubility determination
Separately adding the solid dispersion of the nucleoprotein penicillin-PVP-k 30 into a conical flask with a plug containing a proper amount of the solution A, shaking for 30min at 25 ℃ and 100r/min, respectively sampling, filtering by a microporous membrane with the size of 80 mu m, and measuring the absorbance at 278nm at 25 ℃ according to a spectrophotometric method to calculate the solubility of sclerotropin.
Results of the experiment
The results show that: the maximum absorption wavelength of the nucleopolypenicillin is near 278 nm; at this wavelength, PVP-k30 did not interfere, so 278nm was defined as the measurement wavelength for ribbing penicillin. The solubility of the nucleoprotein penicillin solid dispersion at 25 ℃ is shown in the table, and PVP-k30 is used for preparing the nucleoprotein penicillin solid dispersion, and the proper ratio is 1: 6.
It is thus understood that the solid dispersion of penicillin can improve the water solubility and oral absorbability of the compound.
Various corresponding changes and modifications can be made by those skilled in the art according to the above technical solutions and concepts, and all such changes and modifications should be included in the scope of the present invention as claimed.
Claims (5)
1. A method for preparing a solid dispersion of penicillin, comprising the steps of:
s1, weighing the nucleoprotein penicillin and PVP-k30 in proportion;
s2, adding ethanol to dissolve the nucleoprotein and PVP-k30 to form a mixed solution;
s3 stirring the mixture vigorously until it is clear;
s4, placing the clear mixed solution obtained in the step S3 in a rotary evaporator to remove ethanol;
s5, after freezing and solidifying, placing the mixture into a vacuum drying box for vacuum drying;
s6, crushing the dried mixture to obtain the solid dispersion of the penicillin; wherein the mass ratio of the Pleurotin to the PVP-k30 is 1:4, 1:6 or 1: 8.
2. The method for preparing a solid dispersion of nucleate plexus penicillin as set forth in claim 1, wherein an operating temperature of the rotary evaporator is 65 ℃.
3. The method for preparing a solid dispersion of nucleate plexus penicillin as set forth in claim 1, wherein the temperature of vacuum drying is 40 ℃ and the drying time is 24 hours.
4. Use of the solid dispersion of penicillin prepared by the process of claim 1 for the preparation of a medicament comprising the solid dispersion of penicillin.
5. The use of claim 4, wherein the medicament comprises penicillin and PVP-k30 in a mass ratio of 1: 6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202110072837.7A CN112870166B (en) | 2021-01-20 | 2021-01-20 | Nuclear plexus penicillin solid dispersion, preparation method and application |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202110072837.7A CN112870166B (en) | 2021-01-20 | 2021-01-20 | Nuclear plexus penicillin solid dispersion, preparation method and application |
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| CN112870166A CN112870166A (en) | 2021-06-01 |
| CN112870166B true CN112870166B (en) | 2022-04-08 |
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| CN100340238C (en) * | 2005-06-09 | 2007-10-03 | 中山大学 | Curcumin solid dispersion, and its preparing method and use |
| CN101205234B (en) * | 2007-12-14 | 2010-12-29 | 中山大学 | Curcumin-zinc compound as well as solid dispersion preparation and uses thereof |
| NZ710757A (en) * | 2013-02-08 | 2020-04-24 | Luoda Pharma Ltd | Methods of treating microbial infections, including mastitis |
| US10449195B2 (en) * | 2016-03-29 | 2019-10-22 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical formulation of palbociclib and a preparation method thereof |
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