A kind of preparation method of oral amoxicillin pH-responsive nanocarrier and product thereof

A nano-carrier and amoxicillin technology, applied in the field of medical biomaterials, can solve the problems of cumbersome preparation process, long drug release time, gastric mucosal irritation, etc., to overcome complex operation and release difficulties, improve drug utilization, biological good compatibility effect

Active Publication Date: 2021-02-12
JIANGNAN UNIV
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  • Abstract
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  • Application Information

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Problems solved by technology

Although the existing drug carriers prepared by polymers can improve the solubility and stability of drugs in the digestive tract and blood, these systems have certain defects: it takes about 24 to 48 hours for the drug to be released from sustained release to complete release.
The reality is that the stagnation time of the drug in the intestinal tract is only about 3-20h, so the utilization rate of the drug will be low
In 2013, the Chinese patent CN 102698279B announced the preparation of an amphiphilic γ-polyglutamic acid nanocarrier, but after the drug was loaded, it released 40% of the drug after about 80 hours at pH 7.4, which is not suitable for oral drug delivery systems
Chinese patent CN107496360A has announced the method for preparing amoxicillin sustained-release agent with polyester, acetate, polyethylene glycol etc., although improved the water solubility of amoxicillin, preparation process is loaded down with trivial details, and the medicine sustained-release time is longer, not easy Suitable for human oral drug delivery system
In 2016, the Chinese patent CN105919978B used PLGA (polylactic acid-glycolic acid copolymer) to prepare amoxicillin microsphere capsules. Although it has pH responsiveness, it can only release the drug completely at pH 7.2 for 72 hours, which reduces the drug’s excretion in the intestinal tract. Utilization
Chinese patent CN101889984A uses carboxymethylcellulose sodium, cellulose acetate titanate (CAP) and the like to prepare amoxicillin enteric solution. Although it can control the drug from being released in the stomach, the preparation process is complicated and requires many chemical reagents. Poor biocompatibility, not conducive to human oral system
Existing amoxicillin gastric-soluble oral preparations, that is, amoxicillin is released in the acidic environment of gastric juice, but such preparations are likely to cause irritation to the gastric mucosa, causing various adverse reactions such as abdominal pain and nausea, and are not suitable for patients with Patients with stomach problems use

Method used

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  • A kind of preparation method of oral amoxicillin pH-responsive nanocarrier and product thereof
  • A kind of preparation method of oral amoxicillin pH-responsive nanocarrier and product thereof
  • A kind of preparation method of oral amoxicillin pH-responsive nanocarrier and product thereof

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Experimental program
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Effect test

preparation example Construction

[0030] (1) Preparation of γ-PGA / CS NPs: Add 0.1-5g / L polyglutamic acid aqueous solution dropwise to 0.1-1.0g / L chitosan at a rate of 2-10ml / h with a micro-injection pump In the aqueous solution, stir overnight at room temperature at 600-800rpm, adjust the pH to 2.5, 4.0, 5.0, 6.0, and 7.4 with 2M hydrochloric acid and 2M sodium hydroxide, and measure the potential and particle size at different pHs with a Malvern nanoparticle size analyzer.

[0031](2) Preparation of γ-PGA / CS-Amoxicillin NPs: Mix amoxicillin (1-4g / L) and 2-6g / L polyglutamic acid aqueous solution evenly, and use a micro-injection pump to mix the mixture according to 2- Add 10ml / h dropwise to 0.1-0.5g / L chitosan aqueous solution, stir overnight at room temperature, away from light, at 600-800rpm, place it in a dialysis bag (MWCO=8000-14000), and dialyze into the dialysate The UV absorption of amoxicillin was not detectable. Drug-loaded nanoparticles were obtained by freeze-drying, and the size and shape of γ-PG...

Embodiment 1

[0048] Preparation of γ-PGA / CS NPs(+) and γ-PGA / CS NPs(-):

[0049] Add 0.1-5g / L polyglutamic acid aqueous solution dropwise to chitosan aqueous solution with different concentrations (0.1-1.0g / L) at a rate of 2-10ml / h with a micro-syringe pump, at 25°C, 600- Stir at 800rpm overnight, adjust the pH to 2.5, 4.0, 5.0, 6.0, 7.4 with 2M hydrochloric acid and 2M sodium hydroxide, and measure the potential and particle size at different pHs with a Malvern Nanoparticle Sizer. Finally, two kinds of γ-PGA / CS NPs with a particle size of 200 nm and positive and negative charges on the surface were selected as the carrier for amoxicillin drug embedding. The particle size of γ-PGA / CSNPs was about 200 nm at pH 2.5, and at pH 7.4 is about 800nm.

[0050] Table 1: Effect of γ-PGA concentration on particle size of γ-PGA / CS NPs

[0051]

[0052]

[0053] Table 2: Effect of CS concentration on particle size of γ-PGA / CS NPs

[0054]

[0055] Table 3: Selection of drop rate

[0056] ...

Embodiment 2

[0065] Preparation of γ-PGA / CS-Amoxillin NPs(+) and γ-PGA / CS-Amoxicllin NPs(-):

[0066] Amoxicillin (1-4g / L) and the molecular weight of 2-6g / L are the polyglutamic acid aqueous solution mixing more than 700,000 Daltons, according to the method for embodiment 1 its mixture is used micro-injection pump (needle) 0.1-0.2mm inner diameter, 0.2-0.6mm outer diameter) dropwise into 0.1-0.5g / L chitosan aqueous solution at 2-10ml / h, room temperature, dark, 600-800rpm stirring overnight to prepare γ-PGA / CS-Amoxicillin NPs, put it in a dialysis bag (MWCO=8000-14000) and dialyze until no UV absorption of amoxicillin can be detected in the dialysate, then freeze-dry to obtain γ-PGA / CS-AmoxicillinNPs loaded with amoxicillin , to observe its appearance with a scanning electron microscope, and at the same time dissolve it with a citric acid buffer solution of pH 2.5 to prepare a 1 mg / ml solution, and use a transmission electron microscope to observe the appearance of the solution. (Such as...

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Abstract

The invention discloses a preparation method of oral amoxicillin pH-responsive nano-carrier and its products, which include mixing: mixing amoxicillin, polyglutamic acid and water; dropping: after mixing, amoxicillin 1. Add polyglutamic acid aqueous solution dropwise to chitosan aqueous solution; dialysis: after adding dropwise, place it in a dialysis bag for dialysis. The nanoparticles prepared by the present invention are negatively charged, and can bind drugs through surface adsorption, internal hydrogen bonding and electrostatic adsorption, and overcome the problems of complex operation and difficult release of traditional chemical drug loading, and achieve drug delivery through electrostatic complexation of drugs. The pH-responsive release realizes the ideal state of low drug release in the stomach and high intestinal release. The invention realizes that the nanoparticle loaded with amoxicillin has a low release amount under gastric acid conditions and complete release under intestinal physiological conditions, reduces the stimulation of the drug to the stomach, increases the sustained release time of the drug in the intestinal tract, and improves the drug release rate. utilization rate.

Description

technical field [0001] The invention belongs to the technical field of medical biomaterials, and in particular relates to a preparation method of an oral amoxicillin pH-responsive nano-carrier and a product thereof. Background technique [0002] Compared with injection, oral administration is a more convenient, painless, and infection-free way of administration. The process is that the drug enters the stomach from the mouth, then enters the intestinal tract, is absorbed by the intestinal tract and enters the whole body blood circulation. Although the existing drug carriers prepared by using polymers can improve the solubility and stability of drugs in the digestive tract and blood, these systems have certain defects: it takes about 24 to 48 hours for the drug to be released from sustained release to complete release. The reality is that the stagnation time of the drug in the intestinal tract is only about 3-20h, so the utilization rate of the drug will be low. In 2013, the...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K47/34A61K47/36A61K47/61A61K47/64A61K31/43A61P31/04
CPCA61K9/146A61K31/43A61K47/61A61K47/64A61P31/04
Inventor 陈鹏程郑璞任东雪
Owner JIANGNAN UNIV
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