Capsule polyurethane drug controlled release body with temperature control switch, and preparation method thereof

A technology of drug controlled release and temperature control switch, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, etc., to achieve free adjustment of drug release, fast temperature response, and repeatability Good results

Inactive Publication Date: 2013-07-31
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005]Although it has the objective advantages of the above two aspects when used as a drug controlled release body, the drug release characteristics of common temperature-sensitive polymers have many defects, such as: (1) The temperature-sensitive switches of some temperature-responsive interpenetrating network hydrogels are not sensitive enough, and the response time to environmental temperature changes is too long, which takes several hours (E.S. Matsuo, J. Chem. Phys. i>, 1988, 89: 1695.); (2) The temperature-sensitive switch of some cellulose derivative-based temperature-sensitive materials has poor repeatability, and its switch is easily lost during temperature oscillation (H. Todd, Nano Lett., 2009, 9: 3651.); (3) It is difficult to adjust the drug release amount of some thermosensitive liposomes (H. Todd, Nano Lett., 2009, 9: 3651.); (4) Certain temperature-sensitive polymers, such as poly(N-isopropylacrylamide), also have physiological toxicity, which may cause tissue damage after implantation in the human body Secondary injury (L. Xavier, Adv. Mater., 2010, 22: 5024.), and the above-mentioned controlled release body has a low drug load, which cannot meet the clinical requirements for long-term drug release. It can be seen that the comprehensive performance of common temperature-sensitive polymer-based drug controlled release bodies still has a large gap from the ideal.

Method used

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  • Capsule polyurethane drug controlled release body with temperature control switch, and preparation method thereof
  • Capsule polyurethane drug controlled release body with temperature control switch, and preparation method thereof
  • Capsule polyurethane drug controlled release body with temperature control switch, and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0035] (1) Add 50 parts of polycaprolactone diol with a number-average molecular weight of 4000, 15 parts of 2,4-toluene diisocyanate and 50 parts of N,N-dimethylformamide into the reaction vessel, and keep stirring and Under the protection of nitrogen atmosphere, the temperature of the system was raised to 80°C for 2.5 hours to prepare the NCO-terminated prepolymer;

[0036] (2) After the first step of reaction is completed, slowly add 6.6 parts of 1,4-butanediol chain extender and 110 parts of dimethyl sulfoxide dropwise, and maintain the reaction at 80°C for 2.3 hours to prepare a temperature-sensitive polyurethane solution;

[0037] (3) Pour the obtained temperature-sensitive polyurethane solution into a special mold to prepare a polyurethane pouch with an opening, and place it at 40-50°C until the solvent volatilizes slowly for 5-15 minutes, so that the outer wall of the pouch-shaped polyurethane is solidified and formed, which is about half The solidified temperature-se...

Embodiment 2

[0041] (1) 20 parts of polyethylene adipate diol with a number average molecular weight of 2000, 30 parts of polycarbonate diol with a number average molecular weight of 10000, 4,4'-diphenylmethane diol 19.5 parts of isocyanate and 60 parts of dimethyl sulfoxide were added to the reaction vessel, and under continuous stirring and nitrogen atmosphere protection, the system was heated to 70°C for 2.3 hours to prepare the NCO-terminated prepolymer;

[0042] (2) After the first step reaction is completed, add 5.0 parts of 1,3-propanediol chain extender and 80 parts of N,N-dimethylformamide in sequence, and maintain the reaction at 74°C for 2.5 hours to prepare a thermosensitive Polyurethane solution;

[0043] (3) Pour the obtained temperature-sensitive polyurethane solution into a special mold to prepare a polyurethane pouch with an opening, and place it at 40-50°C until the solvent volatilizes slowly for 5-15 minutes, so that the outer wall of the pouch-shaped polyurethane is sol...

Embodiment 3

[0047] (1) 15 parts of polybutylene adipate diol with a number average molecular weight of 6000, 35 parts of polycaprolactone diol with a number average molecular weight of 8000, 10 parts of 2,4-toluene diisocyanate and Add 30 parts of N,N-dimethylformamide into the reaction vessel, and raise the temperature of the system to 77°C for 2 hours under the protection of continuous stirring and nitrogen atmosphere to prepare the NCO-terminated prepolymer;

[0048] (2) After the first step reaction is completed, 6 parts of 1,6-hexanediol chain extender and 110 parts of N,N-dimethylformamide are added in sequence, and the reaction is continued at 70°C for 2 hours to prepare Thermosensitive polyurethane solution;

[0049] (3) Pour the obtained temperature-sensitive polyurethane solution into a special mold to prepare a polyurethane pouch with an opening, and place it at 40-50°C until the solvent volatilizes slowly for 5-15 minutes, so that the outer wall of the pouch-shaped polyurethan...

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Abstract

The invention discloses a capsule polyurethane drug controlled release body with a temperature control switch. The capsule polyurethane drug controlled release body is prepared by loading the drug by a temperature-sensitive polyurethane capsule pipe. In the application of the capsule polyurethane drug controlled release body, a drug release characteristic with temperature response is expressed; and an 'open-close' effect is present. The capsule wall polyurethane molecules are in a rigid crystalline state below the switch temperature, so that diffusion and release of the drug in the controlled release body are blocked; when the temperature rises to higher than the switch temperature, the polyurethane molecules are in a molten state, so that the drug in the body migrates to the capsule wall and the capsule wall drug release outward continuously, with the concentration as a mass ladder force. Besides, the special design of the capsule wall can realize ideal drug diffusion capacity. The invention also discloses a preparation method of the capsule polyurethane drug controlled release body. The temperature-sensitive polyurethane capsule pipe of the drug controlled release body and unsymmetrical structure of the capsule wall design makes the drug controlled release body have fast temperature response speed, good repeatability of the drug release switch, freely adjustable drug release amount, capacity of uniform drug release, no physiological toxicity, so that the drug controlled release body has wide application prospects in clinic local drug treatment.

Description

technical field [0001] The invention belongs to the field of preparation technology and functional shape design and preparation of capsule polyurethane drug controlled release body with temperature control switch, and specifically relates to a capsule polyurethane drug controlled release body with temperature control switch and its preparation method and application. Background technique [0002] Implanted drug-releasing body with drug-release switch has always been the object of research, and people have reported great enthusiasm for it for more than ten years. Clinically, this new type of intelligent drug release device is very useful for changing the administration of drugs that need to be taken for life or for a long time, such as contraceptives, hypoglycemic drugs, and immunosuppressants for organ transplantation, and improving patient compliance and quality of life. big help. At the same time, the device is also particularly suitable for drugs that require local admi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K45/06C08G18/66C08G18/42C08G18/32C08G18/10
Inventor 徐辉史锐赖俊秀常金明黄乙洳陈意范浩军
Owner SICHUAN UNIV
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