CN103880966B

CN103880966B - The preparation method of special Vltra tears is released in slow control

Info

Publication number: CN103880966B
Application number: CN201410144014.0A
Authority: CN
Inventors: 毕英德; 毕于东; 毕心德; 邱建军; 毕研恒; 王荣新
Original assignee: HEDA CO Ltd SHANDONG
Current assignee: Shandong Heda Group Co ltd
Priority date: 2014-04-11
Filing date: 2014-04-11
Publication date: 2016-06-01
Anticipated expiration: 2034-04-11
Also published as: CN103880966A

Abstract

The invention belongs to Mierocrystalline cellulose preparing technical field, it is specifically related to the preparation method that special Vltra tears is released in a kind of slow control. Cellulose pulp is joined in the solvent containing phase-transfer catalyst, then add sodium hydroxide, propylene oxide and methyl chloride infiltration, then carry out etherification reaction, react complete and obtain Vltra tears slip; Vltra tears slip is by, after rising temperature reclamation solvent, obtaining Vltra tears, then obtains finished product through washing separation drying. The present invention mainly improves the reaction conditions in Vltra tears preparation process, add phase-transfer catalyst fatty alcohol-polyoxyethylene ether, make it reaction more to relax, evenly, low temperature osmotic makes it fully immerse cellulose pulp inside, products obtained therefrom solubility property is improved significantly, so when being used in sustained-release preparation, it is possible to show outstanding slow controlled release properties, obtain good effect.

Description

The preparation method of special Vltra tears is released in slow control

Technical field

The invention belongs to Mierocrystalline cellulose preparing technical field, it is specifically related to the preparation method that special Vltra tears is released in a kind of slow control.

Background technology

Slow release, controlled release preparation be the class novel form starting development in recent years, mean that on purpose Drug controlled release is to reach a class form of administration of ideal treatment. Sustained release preparation mean medication after can in a long time sustained release medicine with reach extend drug effect object preparation. Generally should regulation release medium in, can on request slowly non-constant velocity release medicine, the release of medicine mainly first-order rate process. Controlled release preparation means the preparation that medicine automatically can discharge within the time of setting with the speed set. Generally should in the release medium of regulation, can constant speed or close to constant release medicine slowly on request, the release of medicine mainly Zero order rate process. Hypromellose is the non-ionic celluloses ether class auxiliary material of a kind of domestic and international widespread use, is one of current both at home and abroad pharmaceutical excipient that consumption is maximum, as the pharmaceutical excipient history of existing more than 30 year. The product of hydroxypropyl and methoxyl group etherificate while that it being cellulosic molecule, the displacement group in its molecule is ether class. It is easily molten in cold water without smelly, tasteless, nontoxic, gelation in the hot water. Vltra tears dissolves in gastrointestinal fluid, have that compressibility is good, good fluidity, Drug loading capacity be strong and drug release feature not by advantages such as pH affect, be hydrophilic support material extremely important in sustained release preparation system. But domestic all Vltra tearss for sustained-release preparation at present are external import, domestic each producer is due to production technology reason, and the release that its product all can not reach required in actual experiment and application requires and normally cannot use in this field. Summary of the invention

It is an object of the invention to provide the preparation method that special Vltra tears is released in a kind of slow control, scientific and reasonable, simple, product can be improved for sustained-release preparation, reach required release performance.

The preparation method of special Vltra tears is released in slow control of the present invention, and step is as follows:

(1) cellulose pulp is joined in the solvent containing phase-transfer catalyst, then add sodium hydroxide, propylene oxide and methyl chloride infiltration, then carry out etherification reaction, react complete and obtain Vltra tears slip;

(2) Vltra tears slip is by, after rising temperature reclamation solvent, obtaining Vltra tears, then obtains finished product through washing separation drying.

The granularity of the cellulose pulp described in step (1) is 5-150 micron.

Cellulose pulp described in step (1) is wood pulps or the cotton slurry dregs of rice.

Phase-transfer catalyst described in step (1) is fatty alcohol-polyoxyethylene ether, and the quality of phase-transfer catalyst is the 0.1-0.5% of solvent quality.

Solvent described in step (1) is the mixture of ethanol and toluene, and the mass ratio of ethanol and toluene is 1:3-5.

The mass ratio of the cellulose pulp described in step (1), sodium hydroxide, propylene oxide, methyl chloride and solvent is 1:0.3-0.45:0.3-0.5:0.8-1.2:10-20.

Infiltration temperature described in step (1) is 10-25 DEG C, and penetration time is 20-60 minute.

Etherification reaction described in step (1) is divided into three steps to carry out, temperature of reaction is respectively 40-55 DEG C, 65-75 DEG C, 85-95 DEG C, reaction pressure is respectively 0.1-0.4MPa, 0.3-0.5MPa, 0.4-0.6MPa, and the reaction times is respectively 60-120 minute, 90-180 minute, 30-90 minute.

The present invention compared with prior art, has following useful effect:

The present invention mainly improves the reaction conditions in Vltra tears preparation process, before reaction, cellulose pulp must be crushed to granularity in advance to being less than 150 microns, just can make it to obtain fully in hereafter process, evenly react, and add phase-transfer catalyst fatty alcohol-polyoxyethylene ether, make it reaction more to relax, evenly, at low temperature osmotic 20-60 minute of 10-25 DEG C, it is made fully to immerse cellulose pulp inside, the consumption of solvent must control cellulose pulp amount 10-20 doubly, to improve the homogeneity of its reaction, products obtained therefrom solubility property is improved significantly, so when being used in sustained-release preparation, outstanding slow controlled release properties can be shown, obtain good effect. therefore, this preparation method is that the advanced technologies produced with Vltra tears is released in slow control, domestic slow control is released and is significant with the successful production of Vltra tears.

Embodiment

Below in conjunction with embodiment, the present invention is described further.

Embodiment 1

(constituent mass is than being ethanol: toluene=1:4) to add solvent 15 parts in a kettle., fatty alcohol-polyoxyethylene ether 0.03 part, add wood pulps 1 part, temperature is controlled after 16 DEG C, add 0.45 part, sodium hydroxide, propylene oxide 0.4 part, methyl chloride 1 part, permeating and be warming up to 45 DEG C after 30 minutes, reaction pressure, at 0.1-0.2MPa, reacts timing 80 minutes; Being warming up to 70 DEG C again, reaction pressure, at 0.3-0.5MPa, reacts timing 120 minutes; Being warming up to 90 DEG C, reaction pressure, at 0.4-0.6MPa, reacts timing 80 minutes. Mixture is separated after terminating by reaction, and recycling design re-uses, and then in acetic acid and after regulating PH to 6-7, adds water washing, drier after separation, obtains slow control and releases special Vltra tears product 1.21 parts. Through sustained-release preparation application experiment, its sustained release performance is obviously better than conventional products, reaches current import special product level, and slow controlled-release effect meets requirement completely.

Embodiment 2

(constituent mass is than being ethanol: toluene=1:3) to add solvent 20 parts in a kettle., fatty alcohol-polyoxyethylene ether 0.02 part, add wood pulps 1 part, temperature is controlled after 12 DEG C, add 0.4 part, sodium hydroxide, propylene oxide 0.35 part, methyl chloride 0.9 part, permeate after 60 minutes, be warming up to 55 DEG C, reaction pressure, at 0.2-0.4MPa, reacts timing 60 minutes; Being warming up to 75 DEG C again, reaction pressure, at 0.3-0.6MPa, reacts timing 90 minutes; Being warming up to 95 DEG C, reaction pressure, at 0.4-0.6MPa, reacts timing 30 minutes. Mixture is separated after terminating by reaction, and recycling design re-uses, and then in acetic acid and after regulating PH to 6-7, adds water washing, drier after separation, obtains slow control and releases special Vltra tears product 1.18 parts. Through sustained-release preparation application experiment, its sustained release performance is better than conventional products, reaches current import special product level, and slow controlled-release effect meets requirement completely.

Embodiment 3

(constituent mass is than being ethanol: toluene=1:5) to add solvent 10 parts in a kettle., fatty alcohol-polyoxyethylene ether 0.05 part, add the cotton slurry dregs of rice 1 part, temperature is controlled after 15 DEG C, add 0.42 part, sodium hydroxide, propylene oxide 0.38 part, methyl chloride 0.88 part, permeate after 40 minutes, be warming up to 40 DEG C, reaction pressure, at 0.1-0.2MPa, reacts timing 120 minutes; Being warming up to 65 DEG C again, reaction pressure, at 0.3-0.4MPa, reacts timing 180 minutes; Being warming up to 85 DEG C, reaction pressure, at 0.4-0.6MPa, reacts timing 90 minutes. Mixture is separated after terminating by reaction, and recycling design re-uses, and then in acetic acid and after regulating PH to 6-7, adds water washing, drier after separation, obtains slow control and releases special Vltra tears product 1.20 parts. Through sustained-release preparation application experiment, its sustained release performance is better than conventional products, reaches current import special product level, and slow controlled-release effect meets requirement completely.

Claims

1. one kind is delayed the preparation method that special Vltra tears is released in control, it is characterised in that step is as follows:

(2) Vltra tears slip is by, after rising temperature reclamation solvent, obtaining Vltra tears, then obtains finished product through washing separation drying;

The granularity of the cellulose pulp described in step (1) is 5-150 micron;

Phase-transfer catalyst described in step (1) is fatty alcohol-polyoxyethylene ether, and the quality of phase-transfer catalyst is the 0.1-0.5% of solvent quality;

Solvent described in step (1) is the mixture of ethanol and toluene, and the mass ratio of ethanol and toluene is 1:3-5;

2. the preparation method of special Vltra tears is released in slow control according to claim 1, it is characterised in that the cellulose pulp described in step (1) is wood pulps or the cotton slurry dregs of rice.

3. the preparation method of special Vltra tears is released in slow control according to claim 1, it is characterised in that the mass ratio of the cellulose pulp described in step (1), sodium hydroxide, propylene oxide, methyl chloride and solvent is 1:0.3-0.45:0.3-0.5:0.8-1.2:10-20.

4. the preparation method of special Vltra tears is released in slow control according to claim 1, it is characterised in that the infiltration temperature described in step (1) is 10-25 DEG C, and penetration time is 20-60 minute.