CN1320645A

CN1320645A - Process for preparing, purifying and testing medical hydrogel of polyacrylamide

Info

Publication number: CN1320645A
Application number: CN 00107131
Authority: CN
Inventors: 郑永碧
Original assignee: Individual
Current assignee: Individual
Priority date: 2000-04-21
Filing date: 2000-04-21
Publication date: 2001-11-07
Anticipated expiration: 2020-04-21
Also published as: CN1116321C

Abstract

A process for preparing the hydrogel of polyacrylamide and testing its purity includes adding purity indicating agent, mixing with acrylamide, cross-linking agent and promoter solution, filtering, adding initiator and secondary distilled water, still standing for 0.5-1 hr to obtain said hydrogel, stirring for breaking it, leaching in secondary distilled water several times, and detecting the presence of chlorine ions in extracted liquid to indirctly calculate the content of residual acrylamide monomer in said hydrogel. Its advantages are simple operation, low cost and high quality of product.

Description

Preparation and purification test method of medical polyacrylamide hydrogel

The invention relates to a preparation and purification technology of special chemicals, in particular to a preparation and purification test method of medical polyacrylamide hydrogel.

The Polyacrylamide (PAM) industry has begun to develop in the fifties. PAM and its derivatives are prepared by polymerization of Acrylamide (AM). The production process of aqueous solution polymerized colloid PAM is the earliest method but still used up to now, and the process flow is as follows: preparing AM monomer aqueous solution refined by ion exchange, adding polymerizationadditive, adjusting the temperature of the solution to 20-50 ℃, and introducing N₂And (3) introducing gas for 20min to remove oxygen in the solution, adding an initiator solution, and initiating polymerization for 4-8h to obtain a PAM aqueous solution colloid product. PAM has unique chemical and physical properties, and is widely used in water treatment, paper making, oil exploitation, mining and metallurgy, building materials and textile industries, and PAM hydrogel is also used for drug controlled release, artificial organ materials and soft tissue fillers. The residual AM monomer content of PAM may vary depending on the applicationAnd (6) obtaining. For general industrial use, the residual AM monomer content should be less than or equal to 0.5%; for use in the food industry, the residual AM monomer content should be less than or equal to 0.05%; while some countries require less than 0.002% residual AM monomer for medical purposes. However, in the case of conventional polymerization, the AM monomer is only converted to a large extent, with a conversion of about 98% to 99%. The residual AM monomer is reduced by adding different initiators to promote the polymerization reaction to be complete as much as possible. J.P 77990, Sumitomo chemical Co., Ltd., Japan, reports that 0.3% (NH) of a copolymer of AM and sodium acrylate (AA) is used in the production of the copolymer₄)₂S₂O₈、0.06％Feso₄And 0.07 percent of azodiisobutyronitrile, and the residual AM monomer after polymerization is less than 0.02 percent, but still does not meet the medical requirements. Another approach to reduce residual AM monomer is to post-treat the PAM. Generally, a non-toxic additive is kneaded into a PAM polymer to produce a less toxic derivative, but it is difficult to uniformly disperse the additive into the interior of the PAM colloid by kneading, and thus it is difficult to completely remove the residual AM monomer. In addition, solvent extraction methods have beenused to remove residual AM monomer. Such as extracting residual AM from PAM with three mixed reagents of methanol-water, ethanol-water and methanol-water-benzeneA monomer. The method is costly and generally suitable for preparing analytical samples.

The invention aims to improve the existing production process of aqueous solution polymerization colloid PAM, and provides a preparation method and a purification test method of PAM hydrogel with simple and convenient operation, low cost and extremely low content of residual AM monomer.

The purpose of the invention is realized as follows: according to the concentration of PAM hydrogel to be obtained, a certain amount of 40% AM and 2% purification prompting agent NaCl, a certain amount of 1% -2% methylene dipropionamide and a certain amount of 1% -8% tetramethyl ethylenediamine are uniformly mixed, a glass hourglass funnel is used for filtering, a certain amount of 0.4% -4% ammonium peroxodisulfate is added as an initiator for initiating polymerization, secondary distilled water is added to the required PAM gel concentration, and after uniform stirring, the PAM hydrogel is stood in the air for 1 hour at normal temperature.

The purification indicator adopted by the invention can also be replaced by salts which are harmless to human bodies, such as carbonate, acetate, sulfate, lactate and the like. The purification indicator has no effect on the synthesis process and is only ready for later purification. The purification indicator must be used in an amount greater than the residual AM monomer content of the synthesized PAM hydrogel, and generally greater than 2% by weight of the AM amount.

The invention adopts 1-2% of methylene dipropionamide as a cross-linking agent and can also be replaced by 1-3% of glycol acrylate. The invention adopts 1-8% tetramethyl ethylene diamine as accelerant, and can also be replaced by 1-10% diethanolamine or diethanolamine.

The raw materials used for synthesizing 1000ml of PAM hydrogel with different concentrations by adopting the method are as follows:

40% Acrylamide (AM): 50-300ml

2% sodium chloride: 50-150ml

1% -2% methylenebisacrylamide: 15-120ml

1-8% of tetramethylethylenediamine: 15-60ml

0.5% -4% of ammonium peroxodisulfate: 20-80ml

Secondary distilled water: balance of

The PAM hydrogel obtained by the above method has a small amount of residual AM monomer, but does not meet medical requirements, and post-treatment is required to further reduce the content of residual AM monomer. Therefore, the method adopts a secondary distilled water soaking extraction method to remove the residual AM monomer in the PAM hydrogel, and indirectly estimates the content of the residual AM monomer by testing the existence of chloride ions in the extract. The operation process is as follows: the PAM hydrogel synthesized by the method is stirred and crushed into particles with the size of 3-5mm, the particles are put into a container, secondary distilled water with the volume being twice of that of the PAM hydrogel is added for soaking and extraction, chloride ions and residual AM monomer dispersed in the PAM hydrogel are simultaneously dissolved into the secondary distilled water, and the distilled water is replaced once every 24 hours. 10ml of the replaced extract is taken out, 10ml of 25% nitric acid is added for acidification, 10ml of 17 g/L silver nitrate solution is added, and the mixture is placed for 10 minutes after being shaken uniformly. At this point the following chemical reaction will occur:

and (4) continuing soaking and extracting if the extract liquid is settled or becomes turbid, and repeating the test method until the extract liquid is still transparent after silver nitrate is added, and the extract liquid is not different from secondary distilled water through visual observation. According to the method specified in the national standard GB9729-88, chloride ions of less than 0.2ppm cannot be detected by the method. Since the content of chloride ions in the PAM hydrogel is greater than the content of residual AM monomer, it can be assumed that residual AM monomer is also very low when the extract is still clear and transparent after adding silver nitrate. And finally, measuring by using a liquid chromatograph, wherein the content of the residual AM monomer in the PAM hydrogel obtained by adopting the purification test method is less than 0.0004%. Animal experiments prove that the traditional Chinese medicine composition has no sensitization, carcinogenicity and teratogenicity, no acute, chronic and long-term toxicity, no cytotoxicity and no complications caused by being implanted into animals.

The medical PAM hydrogel synthesized by the method does not need to be heated, does not need to be introduced with inert gas, does not need special equipment, and is simple and convenient to operate. When PAM (polyacrylamide) is synthesized to be hydraulic, sodium chloride is added as an indicator, so that the post-treatment purification operation has visual reference, the purification consumption is low, and the product quality can be ensured.

FIG. 1 is a schematic process flow diagram of the present invention.

Example 1: synthesizing PAM hydrogel with the concentration of 4%, and purifying to meet the medical requirements. 100ml of 40% acrylamide and 75ml of 2% sodium chloride are mixed with 38ml of 2% methylene-bis-propionamide and 16ml of 4% tetramethyl-ethylenediamine, filtered by a glass sand funnel, 24ml of 4% ammonium peroxodisulfate is added, secondary distilled water is added to 1000ml, the mixture is stirred uniformly, and the mixture is allowed to stand in the air at normal temperature for half an hour to 1 hour. And (3) stirring and crushing the obtained PAM hydrogel into particles with the size of 3-5mm, putting the particles into a container, adding secondary distilled water with the volume being twice of that of the PAM hydrogel, soaking and extracting, and replacing the distilled water once every 24 hours. Taking 100ml of the replaced extract, adding 10ml of 25% nitric acid for acidification, then adding 10ml of 17 g/L silver nitrate solution, shaking uniformly, and standing for 10 minutes. If the extract solution is precipitated or becomes turbid, the extraction is continued until the extract solution is clear and transparent after adding silver nitrate and is not distinguished from secondary distilled water by visual inspection. And finally, measuring the content of the residual AM monomer by using a liquid chromatograph.

Example 2: synthesizing PAM hydrogel with the concentration of 12%, and purifying to meet the medical requirements. Mixing 300ml of 40% acrylamide and 150ml of 2% sodium chloride with 120ml of 2% methylene-bis-propionamide and 15ml of 4% tetramethyl-ethylenediamine, filtering by using a sand-breaking funnel, adding 75ml of 0.5% ammonium peroxodisulfate, simultaneously adding secondary distilled water to 1000ml, uniformly stirring, and standing for half an hour to 1 hour in the air at normal temperature. The purification method was the same as in example 1.

Example 3: synthesizing PAM hydrogel with the concentration of 2%, and purifying to meet the medical requirements. Mixing 50ml of 40% acrylamide and 50ml of 2% sodium chloride with 15ml of 2% methylene-bis-propionamide and 60ml of 4% tetramethyl-ethylenediamine, filtering by using a sand funnel, adding 30ml of 4% ammonium peroxodisulfate, simultaneously adding secondary distilled water to 1000ml, uniformly stirring, and standing for half an hour to 1 hour in the air at normal temperature. The purification method was the same as in example 1.

Claims

1. A preparation and purification test method of medical polyacrylamide hydrogel is characterized in that matrix acrylamide, a purification indicator, a cross-linking agent and an accelerator solution with certain content and volume are mixed according to required concentration, an initiator is added after filtration, secondary distilled water is added to a certain volume at the same time, the mixture is uniformly stirred, and the mixture is kept stand in the air at normal temperature for half an hour to 1 hour; crushing the obtained polyacrylamide hydrogel, adding secondary distilled water for soaking and extracting for multiple times, and replacing the distilled water once every 24 hours; the extract liquid is taken for testing each time until the test extract liquid is transparent and clear.

2. The method for preparing and purifying test of medical polyacrylamide hydrogel as claimed in claim 1, wherein the matrix is 40% acrylamide 50-300ml, the purification indicator is 2% sodium chloride 50-150ml, the cross-linking agent is 1% -2% methylene bis-propionamide 15-120ml, the promoter is 1% -8% tetramethylethylenediamine 15-60ml, the initiator is 0.5% -4% ammonium peroxydisulfate 20-80ml, and the secondary distilled water is added to 1000 ml.

3. The method for preparing and purifying a medical polyacrylamide hydrogel according to claim 1, wherein the amount of the purification indicator sodium chloride used must be larger than the residual acrylamide monomer content in the obtained polyacrylamide hydrogel, and the purification indicator sodium chloride can be replaced by carbonate, acetate, sulfate or lactate.

4. The method for testing the preparation and purification of the medical polyacrylamide hydrogel as claimed in claim 1, wherein 100ml of extract is acidified by adding 25% nitric acid, 10ml of silver nitrate is added at a concentration of 17 g/l, and the generation of silver chloride precipitate is observed.