JPS6125734B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a hydrophilic polymer compound having a crosslinked structure.

In recent years, as the use of polymeric materials in the medical industry has progressed, interest in hydrophilic polymers has increased.In particular, polymeric materials that are water-insoluble and highly absorbent are used in various membranes, catheters, contact lenses, enzymes, and pharmaceuticals. It came to be used as a packaging material, etc. However, the mechanical properties of such hydrogels deteriorate rapidly as the water content increases, or transparency is lost when trying to increase material permeability. There are few hydrogels that simultaneously satisfy optical properties and material permeability. The present inventors previously proposed a method for obtaining a hydrogel with excellent mechanical properties, optical properties, and permeability by combining a vinyl monomer that produces a hydrophilic polymer with a vinyl monomer that has low copolymerizability. We have discovered a method for producing a polymeric material that meets the above objectives by adding a highly copolymerizable crosslinking agent to each of the vinyl monomers and carrying out crosslinking polymerization (Japanese Patent Laid-Open No. 50-3487). Among the hydrophilic polymers obtained by this method, polymers consisting of methacrylic acid ester and N-vinyl lactam are particularly useful as soft contact lens materials, medical prosthetic materials, and pharmaceutical packaging materials. It is. It was revealed for the first time that the crosslinked copolymer composition of methacrylic acid ester and N-vinyl lactam had excellent properties when produced by the above method, but the present inventors conducted further intensive studies. As a result of continued research, it was discovered that the crosslinked copolymer composition could be produced by an even simpler method. In other words, it has been found that it is not necessary to use two types of crosslinking agents as long as the combination of methacrylic acid ester and N-vinyl lactam is used, and it is possible to produce a polymer having performance superior to that of only one type of crosslinking agent.

The present invention provides a method for producing a water-insoluble and water-swellable polymer compound, which comprises polymerizing a mixture of methacrylic acid ester, N-vinyl lactam, and vinyl methacrylate. . Here, vinyl methacrylate has the function of a crosslinking agent, and methacrylate and N-
By polymerizing vinyl lactam in the presence of vinyl methacrylate, a crosslinked copolymer composition can be produced without causing phase separation during polymerization. The reason why the method of the present invention is possible is that vinyl methacrylate has two types of polymerizable unsaturated double bonds in one molecule. The copolymerizability of methacrylic acid ester and N-vinyl lactam is small, and in the early stage of polymerization, a copolymer mainly composed of methacrylic ester is formed, and in the later stage, a copolymer mainly composed of N-vinyl lactam is formed. is generated. However, the double bond on the methacryloyl side of vinyl methacrylate has a high copolymerizability with methacrylic ester, and N
-Low copolymerizability with vinyl lactam. On the other hand, the double bond on the vinyl ester side has low copolymerizability with methacrylic acid ester and high copolymerizability with N-vinyl lactam. As a result, a copolymer mainly composed of methacrylic acid ester and a copolymer mainly composed of N-vinyl lactam are crosslinked by vinyl methacrylate, suppressing phase separation and highly hydrophilic N- It is thought that this makes it impossible for a copolymer containing vinyl lactam as a main component to elute into an aqueous medium. Furthermore, the method of the present invention has superior effects over the method using two types of crosslinking agents. In other words, in the method of using two types of crosslinking agents, one of the crosslinking agents has two or more double bonds in one molecule that are highly copolymerizable with methacrylic ester, so the methacrylic ester produced at the initial stage of polymerization is the main component. The copolymer becomes a crosslinked polymer, so that the polymerization mixture has poor fluidity in the early stages of polymerization. As a result, internal distortion tends to remain in the final polymerized product. On the other hand, in the method of the present invention, the copolymer mainly composed of methacrylic acid ester produced in the initial stage of polymerization contains vinyl methacrylate as a copolymerization component, but the reactivity of the double bond on the vinyl ester side Therefore, the degree of crosslinking of the copolymer is low, and the fluidity of the polymerization mixture is maintained until relatively late in the polymerization. As a result, the internal strain of the final polymerization product becomes small, and if the polymerization conditions are selected, it is easy to suppress the internal strain to a substantially negligible level.

Methacrylic acid esters that can be preferably used in the present invention include methyl methacrylate, ethyl methacrylate, n-propyl methacrylate, isopropyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, sec-butyl methacrylate and tert-butyl methacrylate. It is. Further, N-vinyllactams that can be preferably used in the present invention include N-vinylpyrrolidone, N-vinylpiperidone and N-vinylpyrrolidone.
- vinyl caprolactam. The charging ratio of methacrylic acid ester and N-vinyl lactam is preferably in the range of 90:10 to 10:90 by weight. Furthermore, a third copolymer component can be added in an amount of 10% by weight or less of the total weight. Examples of the third copolymerization component include acrylic acid esters such as acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, n-propyl acrylate, isopropyl acrylate, n-butyl acrylate, and isobutyl acrylate, acrylonitrile, and styrene. , acrylamide, methacrylamide, vinyl acetate, etc., and those having the effect of improving the hardness, strength and elongation of the polymer according to the purpose without inhibiting the polymerization reaction may be selected as appropriate.

Furthermore, as mentioned above, the present invention is characterized by using vinyl methacrylate as a crosslinking agent, but it is furthermore highly copolymerizable with N-vinyl lactam and copolymerizable with methacrylic ester as a crosslinking agent. Those with low polymerizability may be used in combination. Such crosslinking agents include, for example, divinyl succinate, ethylidene-bis-3-(N-vinyl-2-pyrrolidone), and triallyl isocyanurate. Regarding the amount of crosslinking agent used, vinyl methacrylate is
0.001 to 5 mol%, preferably 0.005 to 1
Use within the range of mol%. When other auxiliary crosslinking agents are used in combination, they are used within a range in which the total of both does not exceed 5 mol% of the total monomers.

To explain the method of the present invention in more detail, methacrylic acid ester, N-vinyl lactam and vinyl methacrylate, optionally a third copolymer component monomer and/or an auxiliary crosslinking agent, and if necessary, a solvent are mixed; Further, a polymerization catalyst is added to conduct the polymerization, and it is preferable to use radical polymerization as the polymerization mode. As a radical polymerization initiator, di-tert-butyl peroxide,
Organic and inorganic peroxides such as ammonium persulfate, azobisisobutyronitrile, azobis2,4-dimethylvaleronitrile, 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile), 1・1'-Azobiscyclohexane-1
-In addition to azo compounds such as carbonitrile, photosensitizers such as acetophenone, benzophenone, xanthone, benzoin, and benzoin ethyl ether are also used. When polymerization is carried out using a conventional thermal polymerization initiator as mentioned above, it is preferable to adopt a temperature-programmed polymerization method, with the initial polymerization temperature suitably ranging from 20 to 50°C and the final polymerization temperature ranging from 90 to 160°C. It is. When the first half of polymerization is carried out by photopolymerization, the initial polymerization temperature is further lowered to 0 or 0.
It can be carried out at 40°C. The polymerization initiator is used in an amount of 0.001 to 1 mol % based on the total monomers. It is also possible to use a combination of two or more thermal polymerization initiators having different decomposition temperatures, or a combination of photopolymerization.

Since the method of the present invention yields a gelled polymer, it is suitable for cast polymerization, and can be molded into blocks, films, tubes, lenses, etc.
Coating on various surfaces is also possible.

The polymer composition obtained by the above method is transparent and swells moderately when immersed in water or physiological saline, but because it has a special composite structure, it does not lose its transparency and may lose its shape or the polymer may It will not dissolve into water. Furthermore, it has excellent strength and flexibility in a hydrated state. Therefore, the polymer composition of the present invention is very useful as a soft contact lens material, a medical prosthetic material, and a pharmaceutical packaging material. Next, examples will be shown. The mixing ratio of raw chemicals is expressed in parts by weight unless otherwise specified.

In addition, the outline of the measuring method of each rate and intensity|strength in an Example is as shown below. For these measurements, the thickness of the obtained polymer cut on a lathe was measured.
Discs of 0.3 to 0.4 mm and diameters of 10 to 12 mm were used.

(1) Linear swelling rate = Balance water-containing disc diameter / Dry disc diameter before swelling (2) Moisture content = Balance water-containing disc weight - Dry disc weight after extraction / Balance water-containing disc polymerization x 100 (1) (2) In order to reach a state of horizontal collision in the measurement, the sample disk was boiled in pure water for 16 hours to sufficiently swell it, and then immersed in pure water at 37°C for 2 hours.

(3) Extracted residual fraction = Dry disc weight after extraction / Dry disc weight before extraction x 100 (Extraction is performed by boiling the above-mentioned pure water for 16 hours) (4) Breaking strength and breaking elongation: Instron type tensile The measurement was carried out on a sample in a water-containing state using a testing machine in a conventional manner.

Example 1 30 parts of methyl methacrylate, 70 parts of N-vinylpyrrolidone, 0.0706 parts of vinyl methacrylate (0.0677 mol% based on total monomers) and 0.015 parts of azobisisobutyronitrile (0.0098 parts based on total monomers)
mol%) were mixed. Pour 80 g of the mixed solution into each Teflon polymerization tube with an inner diameter of 16 mm and a height of 500 mm, replace the atmosphere with nitrogen gas, and seal the tube. Then 45℃
The polymerization tube was immersed in a constant temperature water bath, and after 15 hours, the temperature of the constant temperature bath was increased to 50℃, and then the temperature was increased to 55℃, 60℃, and 60℃ at 1 hour intervals.
The temperature is increased stepwise to 70℃ and 90℃. After 1 hour at 90℃, transfer the test tube to a 120℃ dry heat constant temperature bath.
It is kept at that temperature for 2 hours and then slowly cooled. After cooling, a colorless and transparent polymer solidified into a rod shape with a length of about 320 mm was taken out. The physical properties of the obtained polymer have a water content of 70.4.
%, extraction residue percentage 90.0%, linear swelling ratio 1.50, breaking strength in a water-containing state 20 Kg/cm ² , and breaking elongation 250%. In addition, the transparency in the water-containing state was good. Furthermore, the uniformity and isotropy of the polymer physical properties were confirmed as follows. In other words, a disk perpendicular to the length direction of the polymer rod was cut out along the length direction, and the linear swelling ratio was examined, and it was 1.50 ± 0.01 excluding 10 mm at both ends.
It was within the range of Furthermore, the linear swelling ratio of the disk cut parallel to the length direction was in the range of 1.50±0.01, and the anisotropy was practically negligible.

Example 2 30 parts of methyl methacrylate, 70 parts of N-vinylpyrocdone, 0.0706 parts of vinyl methacrylate (0.0677 mol% based on the total monomers), ethylidene-bis-3
-(N-vinyl-2-pyrrolidone) 0.313 parts (0.135 mol% based on total monomers) and 0.0310 parts azobisisobutyronitrile (based on total monomers)
0.0202 mol%) mixture with an inner diameter of 16 mm and a height of 180 mm.
Place the sample in a polypropylene test tube, replace the atmosphere with nitrogen, and then seal the tube. The test tube was placed in a constant temperature water bath at 45°C, and the temperature was raised stepwise to 90°C under the same conditions as in Example 1. After 1 hour at 90℃, the test tube was transferred to a 120℃ oil bath, and then the oil bath was heated to 140℃ for 30 minutes.
After keeping at ℃ for 1 hour, slowly cool. The physical properties of the polymer thus obtained are as follows. Moisture content
65.3%, extraction residue rate 96.0% linear swelling rate 1.46±0.005,
The breaking strength in a water-containing state was 12 Kg/cm ² and the transparency was very good.

Example 3 70 parts of methyl methacrylate, 30 parts of N-vinylpyrrolidone, 0.0706 parts of vinyl methacrylate, 2.2'-
Azobis(4-methoxy-2,4-dimethylvaleronitrile) 0.0920 parts (0.0321 mol% based on total monomers), 1,1'-azobiscyclohexane-1-
Carbonitrile 0.0100 parts (0.0044 parts for all monomers)
A mixture of mol%) and 0.0500 part of benzoquinone is placed in a glass test tube, the atmosphere is replaced with nitrogen, the tube is tightly capped, and the tube is kept at 25°C for 15 hours in a constant temperature bath. Then 30℃
for 1 hour, then 35℃, 40℃, 45℃ at 30 minute intervals,
The temperature increases to 50℃, 70℃, and 90℃. After 1 hour at 90℃, transfer the polymerization tube to a 120℃ oil bath and increase the bath temperature to 160℃ for 30 minutes.
℃, held there for 1 hour, and then slowly cooled. The physical properties of the obtained polymer are as follows. Moisture content
21.0%, extraction residue rate 96.3%, linear swelling rate 1.08, breaking strength in water-containing state 360 Kg/cm ² , and good transparency.

Example 4 20 parts of ethyl methacrylate, 10 parts of n-butyl acrylate, 70 parts of N-vinylpyrrolidone, 0.0445 parts of vinyl methacrylate (0.045 mol% based on the total monomers), 0.0435 parts of azobisisobutyronitrile (0.0435 parts of total monomers) (0.03 mol % based on the monomers) was placed in a glass test tube, and polymerization was carried out under the same conditions as in Example 2 except for the above. The physical properties of the produced polymer are as follows. Moisture content 72.7%, extraction residual rate 89.5%, linear swelling rate 1.54,
Breaking strength when hydrated is 10Kg/cm ² . Although the transparency is slightly inferior to that of Example 2, it can be said to be transparent.
The hardness was low and the shore was 5 degrees. (Example 2
The hardness of the polymer is Shore - A15 degrees).

Example 5 20 parts of methyl methacrylate, 80 parts of N-vinylpyrrolidone, 0.141 part of vinyl methacrylate (0.137 mol% based on the total monomers), 0.0377 part of azobisisobutyronitrile (0.025 mol% based on the total monomers)
The mixture was placed in a polypropylene test tube, and polymerization was carried out in the same manner as in Example 2 except for the above. The physical properties of the obtained polymer are as follows. The water content was 77.1%, the extraction residue was 92.6%, the linear swelling rate was 1.68, the breaking strength when wet was 4 Kg/cm ² , and the transparency was very good.

Example 6 20 parts of methyl methacrylate, 80 parts of N-vinylpyrrolidone, 0.0353 parts of vinyl methacrylate (0.0343 mol% based on the total monomers), 2.49 parts triallyl isocyanurate (1.00 mol% based on the total monomers), and azobis 0.0377 part of isobutyronitrile (0.025 mol % based on the total monomers) was mixed and placed in a polypropylene test tube, and polymerization was carried out in the same manner as in Example 2 except that the mixture was placed in a polypropylene test tube. The physical properties of the obtained polymer are as follows. Moisture content: 67.4%, extraction residue: 97.5%, linear swelling rate: 1.50, breaking strength in water-containing state: 4Kg/
cm ² and had good transparency.

Comparative Example Polymerization was carried out under the same conditions except that 0.0594 parts of ethylene glycol dimethacrylate and 0.125 parts of diallyl succinate were used in place of vinyl methacrylate in Example 1. The physical properties of the obtained polymer were a water content of 69.4%, an extraction residue ratio of 90.7%, and a breaking strength in a water-containing state of 21 Kg/cm ² . As described above, the average physical properties were almost the same as in Example 1, but the linear swelling ratio upon hydration was significantly different as shown below. That is, when a disk perpendicular to the length direction of the polymer rod was cut out along the length direction and the linear swelling ratio was measured, it was in the range of 1.49±0.01 excluding 25 mm at both ends.
Furthermore, the disk cut parallel to the length direction swelled into an oval shape due to hydration. This is because the linear swelling ratio in the rod axis direction and the direction perpendicular thereto are different, and the linear swelling ratio in the rod axis direction was 1.44±0.01. The polymer obtained by polymerization using the above two types of crosslinking agents has anisotropy in linear swelling ratio. Furthermore, as mentioned above, the ends of the rod-shaped polymer up to 20 mm show a different linear swelling ratio from the center, but the linear swelling ratio in the direction perpendicular to the rod axis is 1.50 or more at the bottom of the polymerization tube and 1.48 or less at the top of the polymerization tube. be. As described above, the nonuniformity in the rod axis direction was also greater when polymerization was performed using two types of crosslinking agents.

Claims (1)

[Claims] 1. A method for producing a hydrophilic polymer compound that is insoluble in water and swells with water, which comprises polymerizing a mixture of methacrylic acid ester, N-vinyl lactam, and vinyl methacrylate.