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Preparation method of SOD active drug carrier wrapped with novel microsphere biological material

A technology of active drugs and new materials, applied in drug combination, drug delivery, pharmaceutical formulation, etc., can solve problems such as low recovery rate, degradation, and frequent administration

Inactive Publication Date: 2016-10-12
邹汉志
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Superoxide dismutase (superoxide dismutase, SOD) is the only enzyme that removes superoxide anion free radicals in organisms, and is the key line of defense for removing oxygen toxicity. Therefore, in clinical practice, SOD has been used as a drug to treat premature infants due to oxygen Respiratory diseases caused by poisoning; other studies have shown that SOD has adjuvant therapeutic effects on nervous and immune system diseases, but SOD as a medicinal enzyme still has the following defects in its application: the molecular weight is too large, the half-life in the body is short, and the Many times, easy to be degraded by protease, low utilization rate, etc. It is not easy to pass through the cell membrane; in order to solve the above problems, domestic researchers try to carry out molecular modification on SOD, and some water-soluble polymer substances such as polyethylene glycol (PEG) are used at home and abroad. , polyacryloymorpholin, dextran, starch, etc. as modification materials, PEG is condensed with E-NH2 in SOD, non-toxic, non-immunogenic, simple activation but low recovery rate
[0005] Compared with the existing technology: Liu Ling, Yuan Qinsheng (2003) prepared superoxide dismutase (SOD) lactic acid-glycolic acid copolymer (PLGA) microspheres by double emulsion solvent evaporation method, and ultrasonic w / o / W compound emulsion solvent volatilization method prepares protein microsphere, is only the impact of preliminary research SOD on microsphere particle size, encapsulation efficiency, in vitro release etc.; StefanoGiovagnolipoly (D, L-lactide-co-glycolide) PLGA makes SOD microsphere, for For polymers with relatively low molecular weight (Mr <10 000), drugs can be uniformly dispersed in nanoparticles, but for polymers with relatively large molecular weight, the application of this technology is limited due to their low solubility or even insolubility. It is necessary to improve and innovate the existing ball making method
[0006] In recent years, the production and application of SOD have shown that the existing enzyme immobilization modification and liposome technology, although they have good enzyme activity and stability, are widely used in pharmaceutical processing, clinical testing and health and epidemic prevention. As a capsule or carrier of microcapsules and microspheres, polysaccharides have been reported quite a lot, and can be used for substances such as hormones, antibiotics, anticancer drugs, vaccines, antigens, and living cells; for the use of chitosan to assist polypeptides and The microencapsulation of proteins and other biochemical substances is a developing and very promising topic; microcapsules or microspheres made of chitosan can increase the stability of proteins and polypeptides and reduce the side effects of drugs in the body , to prolong the curative effect of the drug; at present, the use of chitosan microspheres to encapsulate SOD as a drug carrier for slow-release and controlled-release preparations has not been reported. provide new ways

Method used

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  • Preparation method of SOD active drug carrier wrapped with novel microsphere biological material

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Embodiment 1

[0022] It can be seen from the contents of the invention that a new microsphere biological material wraps SOD drug carrier, which consists of the preparation of blank chitosan microspheres 1, the preparation of SOD chitosan microspheres 2, the drug loading of SOD chitosan microspheres and their Determination of encapsulation efficiency 3, SOD chitosan microsphere drug release test in vitro 4 four steps to complete its preparation method:

[0023] Preparation of blank chitosan microspheres 1: Dissolve 100 g of chitosan in 1000 mL of 2% glacial acetic acid solution, stir magnetically, add Tween-80 1.0 mL, magnetically stir and sonicate, add 30% Na 2 SO 4Solution, until the above solution is turbid, measure the turbidity at 500 min by UV spectrophotometer to determine the formation of microspheres, continue stirring and ultrasonic treatment for 1 h after microspheres are formed, centrifuge, take 10000~12000 r / min, centrifuge After 15 min, the resulting precipitate was resuspende...

Embodiment 2

[0031] Anti-cancer SOD microsphere drug experiment

[0032] (1) Suspend 100 mg of freeze-dried chitosan microspheres in 250 mL of acetate buffer (pH = 6.2), add 5×10 3 U / mLSOD 1.0mL, magnetically stirred at 4°C, centrifuged at 10000~12000r / min to precipitate, the precipitate (microsphere) was washed 3 times with deionized water, dried in vacuum, and stored at 4°C; the precipitate was washed again, purified, and freeze-dried; Collect and combine the centrifugate and washing liquid to obtain drug-loaded microspheres, and the dispersion is called "SOD microsphere combined liquid"; the SOD content in chitosan microspheres is 5KU=10mg or 5.31×10 4 U / g, the encapsulation efficiency was 97.3%; 50000U / g-SOD microspheres were obtained by freeze-drying, and the senses were light blue-green or white dense spheres.

[0033] (2) Natural cumulative drug release rate of magnetic anti-cancer microspheres: Accurately weigh 50 mg of anti-cancer SOD microspheres, 4 parts in total; wash the oil...

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Abstract

The invention discloses a preparation method for encapsulating SOD drug carrier with new microsphere biological materials, which comprises the preparation of blank chitosan microspheres, the preparation of SOD chitosan microspheres, the drug loading capacity of SOD chitosan microspheres and the encapsulation thereof. The determination of sealing rate and the in vitro drug release test of SOD chitosan microspheres completed its preparation; the surface of the SOD chitosan microspheres was observed under an optical microscope to be smooth and uniform, good dispersibility in normal saline, and a particle size range of 1.2~3.8um ; The reaction conditions of the preparation process of SOD chitosan microspheres are mild, no organic solvent is needed, the pH is close to neutral, and the activity loss of SOD is small; the average value of the samples to be tested is 0.3, and the SOD content in chitosan microspheres is 5KU=10mg or 5.31× 10 4 U / g, encapsulation rate 97.3%; The inventive method is suitable for the mass production of SOD health products, beauty enzyme preparation SOD cosmetics in China, and also provides a new technical method for the production and application of SOD medicinal enzyme preparation.

Description

Technical field: [0001] The invention relates to the field of biotechnology of molecular new materials, in particular to using chitosan as a medical-grade SOD biological new material to prepare drug carrier slow-release and controlled-release preparations for drug clinical and anti-cancer high-efficiency drug delivery to provide new ways and new uses. Background technique: [0002] Superoxide dismutase (superoxide dismutase, SOD) is the only enzyme that removes superoxide anion free radicals in organisms, and is the key line of defense for removing oxygen toxicity. Therefore, in clinical practice, SOD has been used as a drug to treat premature infants due to oxygen Respiratory diseases caused by poisoning; other studies have shown that SOD has adjuvant therapeutic effects on nervous and immune system diseases, but SOD as a medicinal enzyme still has the following defects in its application: the molecular weight is too large, the half-life in the body is short, and the Many t...

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K38/44A61K47/36A61P35/00
CPCA61K9/1652A61K9/0002A61K38/44
Inventor 左有权
Owner 邹汉志
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