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Polyurethane drug release controlling body with thermoswitch and preparation method thereof

A technology of drug controlled release and thermosensitive switch, which is applied in the direction of medical preparations of non-active ingredients, antipyretics, and drug combinations, etc. Insufficient sensitivity, comprehensive performance gap and other issues

Inactive Publication Date: 2012-07-18
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, there are many defects in the drug release characteristics of common thermosensitive polymers, for example: (1) some thermosensitive interpenetrating network hydrogels The thermal switch is not sensitive enough, and the response time to the change of ambient temperature is too long, which takes several hours (E.S.Matsuo, J.Chem.Phys., 1988, 89:1695.); (2) some cellulose derivatives The repeatability of thermosensitive switch of thermosensitive material is poor, and its switch loses effect easily (H.Todd, Nano Lett., 2009,9:3651.) in temperature oscillation process; (3) release of some thermosensitive liposomes It is difficult to adjust the dose according to demand (H.Todd, Nano Lett., 2009, 9: 3651.); (4) Some heat-sensitive polymers, such as poly(N-isopropylacrylamide), also have physiological toxicity. The human body may cause secondary damage to the tissue (L. Xavier, Adv. Mater., 2010, 22: 5024.)
It can be seen that the comprehensive performance of common thermosensitive polymer-based drug controlled release bodies is far from the ideal.

Method used

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  • Polyurethane drug release controlling body with thermoswitch and preparation method thereof
  • Polyurethane drug release controlling body with thermoswitch and preparation method thereof
  • Polyurethane drug release controlling body with thermoswitch and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0034] 100 parts of polycaprolactone diol with a number average molecular weight of 4000, 12.5 parts of 4,4'-diphenylmethane diisocyanate and 200 parts of N, N-dimethylformamide were added to the reaction vessel, under continuous stirring and nitrogen atmosphere Under protection, raise the temperature of the system to 80°C and react for 2.5 hours to prepare an NCO-terminated prepolymer; 13.2 parts of diol chain extender and 164 parts of dimethyl sulfoxide, and maintained at 80 ° C for 2.3 hours to continue the reaction to prepare a heat-sensitive polyurethane solution; 0.7 parts of paclitaxel was dissolved in N, N-dimethylformamide to Prepare a uniform drug solution; then blend it evenly with 80 parts of heat-sensitive polyurethane solution; after filtering and defoaming, pour the above-prepared mixture into a mold, and place it at 40°C for 48 hours until the solvent slowly volatilizes; Finally, continue to evaporate the residual solvent at 78° C. and a vacuum of 0.7 mmHg unti...

Embodiment 2

[0037] 20 parts of polyethylene adipate diol with a number average molecular weight of 2000, 60 parts of polycarbonate diol with a number average molecular weight of 10000, 8 parts of 4,4'-diphenylmethane diisocyanate and dimethyl Add 180 parts of sulfoxide into the reaction vessel, and under the protection of continuous stirring and nitrogen atmosphere, raise the temperature of the system to 70°C and react for 2.3 hours to prepare the NCO-terminated prepolymer; after the first step of reaction is completed, add 4,4' -29.0 parts of diphenylmethane diisocyanate, 10.0 parts of 1,3-propanediol chain extender and 36 parts of N,N-dimethylformamide, and maintained at 74 ° C for 2.5 hours to prepare a thermosensitive polyurethane solution; Dissolve 0.5 parts of sulfamethoxazole in dimethyl sulfoxide to prepare a uniform drug solution; then blend it with 75 parts of heat-sensitive polyurethane solution; after filtering and defoaming, pour the above-prepared mixture into a mold and pla...

Embodiment 3

[0040] 25 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, 3 parts of 2,4-toluene diisocyanate and N, N-di Add 150 parts of methylformamide into the reaction vessel, and under continuous stirring and under the protection of nitrogen atmosphere, raise the temperature of the system to 77°C for 2 hours to prepare the NCO-terminated prepolymer; after the first step of reaction is completed, add 2, 16.9 parts of 4-toluene diisocyanate, 12.4 parts of 1,6-hexanediol chain extender, and 65 parts of N,N-dimethylformamide were maintained at 70°C for 2 hours to prepare a heat-sensitive polyurethane solution; Dissolve 0.1 part of lidocaine in N,N-dimethylacetamide to prepare a homogeneous drug solution; then blend it with 50 parts of heat-sensitive polyurethane solution; filter and defoam, the above prepared The mixture was poured into a mold, and placed at 30°C for 24 hours...

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Abstract

The invention discloses a polyurethane drug release controlling body with a thermoswitch, which is prepared by compounding thermosensitive polyurethane with drug micromolecules. The free volume of the thermosensitive polyurethane is subjected to reversible contraction-expansion mutation at a certain temperature from 39 to 45 DEG C so as to have an on-off effect, thus the drug micromolecules loaded in the thermosensitive polyurethane have the characteristic of releasing in response to the temperature, wherein below the on-off temperature, the releasing rate of the drug micromolecules is extremely low; and when the temperature rises to above the on-off temperature, the releasing rate of the drug micromolecules rises dramatically. The invention also discloses the preparation method of the polyurethane drug release controlling body. The polyurethane drug release controlling body can conveniently control the response release of the drug micromolecules through temperature change and is highin response speed and free of physiological toxicity, the repeatability of the release switch is good, and the drug release amount can be adjusted freely, thus the polyurethane drug release controlling body has wide application prospect in treatment on postoperation pain, organ infection, local tumor and other diseases; and the preparation method is simple and mature and is easy to grasp.

Description

technical field [0001] The invention belongs to the technical field of thermosensitive switch drug controlled release body and preparation thereof, and in particular relates to a polyurethane drug controlled release body with thermosensitive switch and a preparation method thereof. Background technique [0002] Over the past decade, there has been a great deal of enthusiasm for the development of implantable controlled drug release bodies with drug release switches. Clinically, this new type of intelligent drug delivery device is especially suitable for the treatment of common diseases such as postoperative pain, organ infection and local tumors. This is because on the one hand, the current specific drugs for these diseases, such as anesthetics, antibiotics and anti-tumor drugs, usually have great side effects, and if they are administered systemically, they will inevitably cause serious damage to other healthy organs of the human body; on the other hand, The commonality of...

Claims

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Application Information

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IPC IPC(8): A61K47/34A61P31/04A61P29/00A61P35/00A61P23/00
Inventor 陈意范浩军徐辉刘世勇石碧
Owner SICHUAN UNIV
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