Unlock instant, AI-driven research and patent intelligence for your innovation.

Triblock copolymer, oral intestinal location type dual-layer drug-loaded microspheres containing triblock copolymer and preparation method

A drug-loaded nano-copolymer technology, applied in the field of nanotechnology and drug controlled release, can solve the problems of oral drug delivery system achieving great results, loss of drug activity, gastrointestinal toxicity, etc., and achieve the effect of increasing the scope of drug utilization

Active Publication Date: 2018-03-13
ANHUI UNIVERSITY
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A series of commonly used chemotherapeutic anticancer drugs such as doxorubicin, cyclosporine and cisplatin will lose the activity of the drug or cause great irreversible toxicity to the gastrointestinal tract through the oral system
However, most of the drug carriers studied at this stage make the drug enter the human body through intravenous injection, and have not achieved great results in the oral drug delivery system.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Triblock copolymer, oral intestinal location type dual-layer drug-loaded microspheres containing triblock copolymer and preparation method
  • Triblock copolymer, oral intestinal location type dual-layer drug-loaded microspheres containing triblock copolymer and preparation method
  • Triblock copolymer, oral intestinal location type dual-layer drug-loaded microspheres containing triblock copolymer and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1 3

[0033] The preparation of embodiment 1 triblock copolymer P (OE-HMDI-CL)

[0034] Under a nitrogen atmosphere, 0.29 g (0.55 mmol) of polycaprolactone with a molecular weight of 530, 0.29 g (1.10 mmol) of 4,4'-dicyclohexylmethane di Isocyanate and 2 mL of dichloromethane reacted for 4 hours under magnetic stirring, then added 2 mL of dichloromethane and 0.17 g (0.55 mmol) of orthoester dihydroxy monomer with a molecular weight of 310.3, and reacted for 24 hours at room temperature. The water was settled three times with ether, washed three times with ethyl acetate, and dried under negative pressure in an oil pump to obtain 0.69 g of polymer P(OE-HMDI-CL), with a yield of 90.17%. 1 H NMR (400MHz, CDCl 3 , δ, ppm): 0.78-1.48 (m, 12H, CH 2 -CH 2 -CH), 1.49-1.79 (m, 12H, CH 2 ), 1.92-2.09 (d, 4H, NH-CH-CH 2 ), 2.24-2.45 (m, 4H, O-CO-NH), 3.32-3.47 (s, 2H, NH-CH), 3.49-3.90 (m, 12H, O-CH 2 ), 3.91-4.12 (m, 8H, CH 2 -O-CO), 4.16-4.28(m, 8H, O-CH 2 -CH 2 -O), 4.29-2.39(d, 2H,...

Embodiment 2

[0038] Example 2 Preparation of oral intestinal-localized double-layer nanosphere carrier A

[0039] After adding the triblock polymer prepared by 40mg of implementation 1 into 2ml of dichloromethane and fully dissolving, it was added to 10mL of 5% carboxymethyl chitosan solution under the condition of vortex, and then ultrasonic (3 time, each time 10 seconds, interval 5 seconds, power 300W), after sonication, immediately added to 20mL of 0.3% polyvinyl alcohol solution, then added 5μL glutaraldehyde, stirred at room temperature for 3h, dichloromethane volatilized, in Under 10000rpm, centrifuge for 10min, the obtained products are respectively dispersed in the phosphate buffer solution of pH = 1.5, 2.5, 3.5, 4.5, 5.5, 6.5, 7.4, 8.5, 9.5, and the trend of potential change is measured by DLS, the results are shown in figure 2 , this result is consistent with the pKa value of carboxymethyl chitosan, indicating that carboxymethyl chitosan coating was successfully prepared. The p...

Embodiment 3

[0040] Example 3 Preparation of oral intestinal-localized double-layer nanosphere carrier B

[0041] After the triblock polymer prepared by 40mg embodiment 1 was added into 2mL of methylene chloride and fully dissolved, it was added to 10mL of 4% carboxymethyl chitosan solution under the condition of vortex, and then ultrasonic ( 3 times, 10 seconds each time, 5 seconds apart, power 300W), after ultrasonication, immediately add to 20mL of 0.3% polyvinyl alcohol solution, then add 5μL of glyoxal, stir at room temperature for 3h, to volatilize dichloromethane. Centrifuge at 10000rpm for 10min, and redisperse with 0.01M pH8.0 buffer solution to obtain nano drug carrier B.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a poly(orthoester-isocyanate-caprolactone) triblock copolymer and oral intestinal location type dual-layer drug-loaded microspheres prepared by taking a mixture of a polymer and a drug as an inner layer and taking carboxymethyl chitosan as an outer layer. The triblock copolymer and a carboxymethyl chitosan coating have good biocompatibility and biodegradability; a nano-drugcarrier prepared from the triblock copolymer can protect a series of drugs to enter blood circulation through an oral system, so that the use range of the drugs is greatly widened. The process of transporting dual-layer nano-microspheres in a body is as follows: protecting an inner layer of a drug-loaded core from being degraded in a stomach environment by using the carboxymethyl chitosan coating; then when the carrier is positioned in an intestinal tract, absorbing the carrier by the small intestine size effect and enabling the carrier to enter the blood circulation. Quick release of the drugs is initiated by using EPR (Effects of Permeability and Retention) and subacid, and further enrichment of an anticancer drug in cancer cells is realized, therefore, the dual-layer nano-drug carrierhas a good application prospect in the field of oral treatment of diseases.

Description

technical field [0001] The invention belongs to the technical field of nanotechnology and drug controlled release, and relates to the synthesis of an acid-sensitive orthoester-containing polymer, the corresponding oral intestinal-localized drug-loaded nano-microsphere with a double-layer structure and a preparation method thereof. Background technique [0002] With the improvement of living standards, the living environment of human beings has become more complex, making cancer one of the diseases that need to be solved more and more urgently. The most widely used anticancer chemotherapeutic drugs currently have many deficiencies, such as: poor solubility, no target tissue selectivity, high toxicity, and irreversible damage to normal tissues. Therefore, more and more studies have been conducted on the drug carrier technology that controls the release of drugs at special sites, especially the nano-drug carrier designed based on the special microenvironment of cancer with low ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C08G18/66C08G18/10C08G18/42C08G18/32A61K9/51A61K45/00A61K47/34A61P35/00
CPCA61K9/5161A61K45/00A61K47/34C08G18/10C08G18/4277C08G18/664C08G18/3218
Inventor 唐汝培孙敏
Owner ANHUI UNIVERSITY