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Preparation method of succinic-anhydride-modified corn prolamin drug-loading particles

A zein and succinic anhydride technology, applied in the field of biomedicine, can solve the problems of affecting the physical and chemical properties and bioavailability of drug molecules, affecting the release and delivery of drugs, easy agglomeration and precipitation, etc. resistance, enhanced force, good dispersion effect

Inactive Publication Date: 2018-12-07
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Zein, as a kind of prolamin, can quickly form small balls by phase separation method. The product obtained by this method has a large particle size and wide distribution, and the absolute value of the Zeta potential of the product is small under physiological conditions, and it is easy to agglomerate and precipitate. Leading to premature release or inability to release the drug, affecting the release and delivery of the drug in the body, the application in drug delivery has great limitations (Shukla R, Cheryan M. Zein: the industrial protein from corn. Industrial Crops & Products, 2001, 13(3):171‐192.), researchers often use dispersants to improve the dispersion of zein, which not only affects the physicochemical properties and bioavailability of drug molecules, but also has problems such as solvent residues

Method used

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  • Preparation method of succinic-anhydride-modified corn prolamin drug-loading particles
  • Preparation method of succinic-anhydride-modified corn prolamin drug-loading particles
  • Preparation method of succinic-anhydride-modified corn prolamin drug-loading particles

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Embodiment 1

[0031] The preparation method of succinic anhydride modified zein drug-loaded granules comprises the following steps:

[0032] (1) Acylation reaction of succinic anhydride and zein: 1 g of zein with a purity of 97% was dissolved in 75 mL of ethanol solution with a volume fraction of 70%, and the pH of the solution was adjusted with 0.1 mol / L NaOH solution to 10-11, then add 0.2 g of succinic anhydride, react at 40°C for 2 hours, keep the pH of the solution at 10-11 during the reaction, and obtain a succinylated zein solution;

[0033] (2) Purification of succinylated zein: adjust the pH of the succinylated zein solution to 6.5-7.0, transfer it to a dialysis bag with a molecular weight cut-off of 8000-14000KD for dialysis, dialysis for 2 days, and change the water in total 10 times, the retentate in the dialysis bag was centrifuged and washed 3 times at a speed of 5000 rpm, and freeze-dried to obtain succinylated zein.

[0034] (3) Preparation of drug-loaded granules: 4 mg cur...

Embodiment 2

[0042] The preparation method of succinic anhydride modified zein drug-loaded granules comprises the following steps:

[0043] (1) Acylation reaction of succinic anhydride and zein: 1 g of zein with a purity of 97% was dissolved in 75 mL of ethanol solution with a volume fraction of 70%, and the pH of the solution was adjusted with 0.1 mol / L NaOH solution to 10-11, then add 0.4 g of succinic anhydride, react at 40°C for 2 hours, keep the pH of the solution at 10-11 during the reaction, and obtain a succinylated zein solution;

[0044] (2) Purification of succinylated zein: adjust the pH of the succinylated zein solution to 6.5-7.0, transfer it to a dialysis bag with a molecular weight cut-off of 8000-14000KD for dialysis, dialysis for 2 days, and change the water in total 10 times, the retentate in the dialysis bag was centrifuged and washed 3 times at a speed of 5000 rpm, and freeze-dried to obtain succinylated zein.

[0045] (3) Preparation of drug-loaded granules: Dissolve...

Embodiment 3

[0049] The preparation method of succinic anhydride modified zein drug-loaded granules comprises the following steps:

[0050] (1) Acylation reaction of succinic anhydride and zein: 1 g of zein with a purity of 97% was dissolved in 75 mL of ethanol solution with a volume fraction of 70%, and the pH of the solution was adjusted with 0.1 mol / L NaOH solution to 10-11, then add 1 g of succinic anhydride, react at 40°C for 2 hours, keep the pH of the solution at 10-11 during the reaction, and obtain a succinylated zein solution;

[0051] (2) Purification of succinylated zein: adjust the pH of the succinylated zein solution to 6.5-7.0, transfer it to a dialysis bag with a molecular weight cut-off of 8000-14000KD for dialysis, dialysis for 2 days, and change the water in total 10 times, the retentate in the dialysis bag was centrifuged and washed 3 times at a speed of 5000 rpm, and freeze-dried to obtain succinylated zein.

[0052] (3) Preparation of drug-loaded granules: 4 mg of hy...

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Abstract

The invention discloses a preparation method of succinic-anhydride-modified corn prolamin drug-loading particles. The method comprises the following steps of: dissolving corn prolamin in dimethyl sulfoxide or ethanol aqueous solution, regulating pH of the solution to 10-11, then mixing with succinic anhydride, reacting for 1-2 hours at a temperature of 40-45 DEG C, keeping the pH of the solution being alkaline in the reaction process, obtaining succinylated corn prolamin liquid, placing the liquid in a dialysis bag for dialysis after reaction is ended, freezing and drying into powdery solid, and dissolving hydrophobic drugs and freeze-dried succinylated corn prolamin in the ethanol aqueous solution; filling hydrochloric-acid aqueous solution under stirring, and after stabilizing, centrifuging to remove supernatant, thus obtaining the drug-loading particles. The preparation method disclosed by the invention has the beneficial effects that the prepared drug-loading particles are high insphericity degree, good in dispersity, narrow in particle-size distribution and uniform in size, the stability is obviously improved compared with unmodified corn prolamin particles under the physiological pH environment, the slow release effect is good, and the prepared drug-loading particles can be used for oral or sucking type administration or be prepared into suspensions for injection use.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a succinic anhydride-modified zein and a method for preparing succinylated zein drug-loaded particles. Background technique [0002] Poor water solubility is one of the main problems that limit the clinical application of many traditional chemotherapeutic small molecule drugs. In recent years, nanotechnology-based drug delivery systems provide a new strategy to overcome the poor water solubility of drugs and improve the pharmacokinetics of hydrophobic drugs in vivo; The advantages of sustained release, controlled release and targeted release. As an important part of the drug delivery system, the selection of drug carrier materials is extremely critical, and the carrier materials are required to have good biocompatibility and biodegradability without affecting the pharmacological effects of the drug. Curcumin, indomethacin, and hydroxycamptothecin are hydrophobic drugs, and the usual ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/42A61K31/4745A61K31/405A61K31/12
CPCA61K9/5169A61K31/12A61K31/405A61K31/4745
Inventor 江燕斌朱炜卢珊
Owner SOUTH CHINA UNIV OF TECH
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