JPS60156706A - Matrix polymer, preparation and utilization thereof - Google Patents

Abstract

PURPOSE:To obtain the titled polymer, easily producible into films and molded articles, and suitable for producing contact lenses, artificial blood vessels, etc., by dissolving a basic type cationic derivative of dextran in an unsaturated acid, and bulk polymerizing the resultant solution. CONSTITUTION:A polymer obtained by dissolving (A) a basic type cationic derivative of dextran, e.g. diethylaminoethyldextran, in (B) an unsaturated acid, e.g. acrylic acid, and bulk polymerizing the resultant solution usually at 20-70 deg.C to polymerize the components (A) with (B).

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention involves matrix polymerization of a cationic derivative of dextran with an unsaturated acid to produce useful polymerization products such as ion complexes and copolymers of ion complexes and vinyl compounds. be.

Dextran is produced by bacteria of the genus Lactovanlieria. Glucose is a repeating unit, mainly formed by (1→6) gelcondo bonds, which makes it very stable in the body and gradually degraded by tissue enzymes, so it has excellent biocompatibility.

Matrix polymerization is a polymerization method proposed by Cargin, in which monomers or...・In the presence of a polymer such as a matrix, etc., pentapolymerization is performed. The polymerization product exists as a complex of polymerized monomers and polymers that become polymers.

Polymers with such intermolecular complexes are useful substances with a wide variety of uses. In particular, inter-polymer ion complexes, which form complexes between polymers, are attracting attention for their applications in oral membranes, biotechnology, and materials.

Particular attention is paid to its hydrophilicity, and potential applications include artificial kidney membranes, components, blood vessel substitutes, and contact lenses.

The cationic derivative of dextran mentioned here has the unit formula: (CIHyO-(OH)--a ・(OX)a)x (
1) [In the formula, X is -(OH,)nR, (B,, is -N
I(t, -N(OH,),'.

=<,c crystal wisdom, -weiC crystal)s, -0,H,・Nagi, -C
O・(3,H,...Group selected from the skin-like group, n=
(an integer from 1 to 8), or -〇〇ru (IR2 is -CHj-nagi or -C6ru・Nllll2) or -CH20H(OH)
・・C ratio (ru is → ratio, -N (0 le h.

-N(0,B)・, JOsHn)・, a positive number of 0<a≦3, an integer of X≧5](1
) is shown by the formula. In addition, some of the hydroxyl groups in dextran are ether-linked to form carboxymethyl groups.

, one substituted with an acidic group such as a sulfate ester group, or one partially substituted with an alkyl group containing a cationic functional group represented by X in the above formula (1).

On the other hand, the unsaturated acids that can be matrix-polymerized are:
The following general formula can be considered. .

11 H-C-0-11t (2) (where it is 02-e having a double bond of unsaturated acid)
(organic group of ta) Specifically, for example, acrylic acid, methacrylic acid, chloric acid, isocrotonic acid.

β,β-dimethylacrylic acid, angelic acid.

A, β-unsaturated acids such as tiglic acid and unsaturated acids such as maleic, fumaric, citraconic, mesaconic, itaconic, aconitic and oleic acids are considered.

The reaction is usually carried out in an aqueous solution, ie, in an aqueous solution of the cationic derivative of dextran, the unsaturated acid is added and an initiator is added. Examples of the initiator include radical initiators such as potassium persulfate (KPS), AIBN, and BPO. The reaction temperature can be selected from a wide range from room temperature to 70°C.

The ionic complex of the polymer produced in this reaction is insoluble in organic solvents such as water, alcohol, acetone, and tetrahydrofuran, making it very inconvenient to form films or make molded products. After some experimentation, it was discovered that the base type of the cationic derivative of dextran was completely or partially dissolved in -J- fusogenic acid.

In this case, the basic form of the cationic derivative of dextran is dissolved in an unsaturated acid, and the base form is dissolved in ordinary azohisisobutylnitrile (AIBN).

Mass polymerization of MAI-'J Sokunu was possible using a common radical initiator such as bency peroxide/I/(BPO), and the reaction temperature could be varied from 20 DEG C. to 70 DEG C. Also, by mixing this cationic derivative of dextran dissolved in an unsaturated acid with other vinyl compounds,
Polymerization is initiated using a radical initiator such as conventional AIBN, BPO, etc. in an amount of about 0.1 to 1.5% of the total amount, and the reaction temperature is usually carried out in the range of 20 ° C to 80 ° C.
It was discovered that by continuing the reaction with nitrogen substitution if necessary, it was possible to obtain a copolymer of this matrix polymer and other vinyl compounds.

This copolymer can be obtained in various rod-like or plate-like shapes, and can be processed into various products by annealing at 80 DEG C. to 100 DEG C., followed by cutting and polishing, if necessary. Examples of this include contact lenses, 2 artificial blood vessels, 1 artificial bones, 1 artificial kidneys, 9 artificial corneas, dentures, and denture bases.

In the matrix polymer, the ratio of the matrix to the unsaturated acid, or when the matrix polymer is copolymerized with another vinyl polymer, the ratio of the 7 Trinks polymer to the vinyl polymer can be variously selected depending on the purpose.

The vinyl compound used here has the following formula: hydrogen, CI to C1 □ alkyl group, cyclohexyl X, and a to C1 hydroxyalkyl group.

C, NC, aminoalkyl group, C1-C8 dialkylaminoalkyl group, glycidyl group.

Tetrahydrofuran group, C, -C, lower alkyl substituted tetrahydrofuran group, benzyl group and (-CH2CI
(-0-)yCBC...0■ group (y is a positive number from 1 to 10), -N(Rlo)l (Rlo is hydrogen alkyl group)
, phenyl group, pyridine group, tolyl group, and pyrrolidone group] Specifically, when acrylic acid and methacrylic acid are used, a
, lower alkyl-substituted cyclohexyl esters such as alkyl esters of β-unsulfuric acid and cyclohexyl esters.

2-Hydroxyethyl ester, 2-hydroxypropyl ester/I/, 2-hydroxybutyl ester; acrylamide, methacrylamide, acrylic- or methacrylic-dimethylamide, C1 to Cs of the above a, ρ fusogenic acid Aminoalkyl ester, dialkylaminoalkyl ester of c+ to Cs.

Glycidyl ester, tetrahydrofurfuryl ester, benzyl ester/L/, polyethylene glycol seven diesters;
LE COLE, METIL VINY LUAR
Cole.

Dimethylvinylalco~/L/; Vinyl acetate.

Vinyl alcohols such as vinyl propionate vinyl butyrate and the 01-C3 alkyls of the above-mentioned methyl-substituted vinyl alcohols include styrene, vinyltoluene; vinylpyridine-vinylpyrrolidone; vinylmethylpyrrolidone and the like.

Example 1 A DEAE dequinutran (diethylaminoethyl) hydrochloride with a nitrogen content of 5% based on dextran with an average molecular weight MW of 500,000 is dissolved in 1f/50 ml of water, and 50 tttl of a 0.75% aqueous solution of sodium methacrylate is added thereto. Potassium persulfate (KPS) solution (8
, 9XIQrnol/, /,) 101111 was added and the reaction was carried out in a sealed tube at a reaction temperature of 80°C for 70 hours. The mixture was then poured into 8 times the amount of acetone, and the resulting polymerization product complex was collected as a precipitate.

After 8 hours of drying under reduced pressure, a polymerized product complex of 0.96F was obtained. Total yield: 70%, nitrogen content: 3.8%. This product was insoluble in water, methanol, and acetone.

Example 2 A 50% caustic soda solution was added to an aqueous solution of the hydrochloride of DEAE dextran (dimethylaminoethyl/L/) with a nitrogen content of 5% using dextran with an average molecular weight MW of 500,000 as a base, and a base precipitated at a pH of 11.0 or higher. DEAE dequinutran 1 (1') of the type is dissolved in methacrylic acid 20%, and this DEAE dequinutran-methacrylic acid solution is further mixed well with methyl methacrylate/L/450., me.
Add 2.5F of mazobisisobutylnitrile (AIBN). The mixture was placed in a glass tube with a diameter of 1511 tH, and after sufficient degassing, the tube was sealed and polymerization was started.

The polymerization temperature is 50° C. After 72 hours of polymerization time, the mixture is heated in an air bath at 80° O for 3 hours. After cooling, the rod-shaped polymer was removed from the glass tube and annealed in an air bath at 80°C for 24 hours to obtain 470 g of bulk polymer. This polymer was insoluble in organic solutions such as acetone, n-hexane, and tetrahydrofuran, as well as in water and methanol.

Vicat Softening Point 98.8°fl (A S TMD 1
525) Rockwell, hardness (B (scale) v, )
86 (A 8TM D785), bending strength K9/
Tomo') 1180 (Autograph IM600. Temperature 2
3°C1 speed, 2m/m, distance between branches 7Q+a
+), Figure 1 is the IR spectrum of this copolymer. When looking at this spectrum, the QB-0 absorption caused by DEAE dextran is seen around 2650, and the C-0 absorption caused by methacrylic acid and methyl methacrylate/l/(MMA) is seen around 1720α. The presence of this copolymer can be confirmed from the fact that it is insoluble in acetone, which is a good solvent for each of poly(methyl methacrylate) and basic DEAE dextran.

Example 3 'Base form DEAE dequinutran 2fM, methacrylic acid 505g/., methacrylate methacrylate/V825tll.

The procedure of Example 2 was repeated except that 8 g of AlnN1' was used to obtain a 380f bulk polymer. Main polymerization, monohacetone,
It was insoluble in organic solvents such as n-hexane and tetrahydrofuran, or in water and methanol.

Vicat softening point 87°C, Rockwell hardness M scale) 68 (A8TM D785) Example 4 Hydrochloride of HPTMA dextran (2-hydroxypropyltrimethylammonium) with average molecular weight MW 80,000 5
g to 100m of water? Dissolve the solution in water, add 50% caustic soda solution to bring the pH to 11.0 or above, and then add 3 times the amount of acetone to form a precipitate. This sediment was dissolved in 20 ml of acrylic acid, 120~ of AIBN was added, and polymerization was carried out in the same manner as in Example 2 to obtain 28 fl of a bulk polymer.

This polymer was insoluble in organic solvents such as acetone, II-hexane, and tetrahydrofuran, or in water and methanol.

Rockwell hardness M scale) 5.0 (AsTMD7
85) Example 5 The rod-shaped block polymer obtained in Example 2 was treated with hot water and dried, then cut with a lathe at 2000 revolutions per minute, processed with an uneven surface at the same rotational speed to determine a constant curvature, and then processed with a lens polisher. Pi-
The contact lens was fitted into JJII and polished at an upper rotation speed of 15 times per minute and an upper rotation speed of 200 times per minute, followed by bevel processing using a bevel machine to obtain a contact lens. The Corlens had a good hydrophilic surface, and the contact surface was 56°.Conventional lenses under similar measurement conditions (polymethyl methacrylate 9 was 72°
It was °.

This is replaced with the next conventional lens (polymethacrylate methacrylate) Ly.
), the left eye visual acuity was 0.01 (1,OXS -4,50), and the right eye visual acuity was 0.01 (1,0x8-4.50), and when it was worn as a power of -4,50, the result was 8. It was a time-worn town. Visual acuity was 1.0 in both eyes.

After wearing this contact lens for one year, the base color
When the power was measured, no change occurred.

The contact lenses used were as follows: Base Color Power Size Left eye 740M scrap -4,508,8ff Right eye 74
5 Tomo - 4,508, 8 questions Example 6 A contact lens was manufactured using the rod-shaped block polymer obtained in Example 4 in exactly the same manner as in Example 5. For those who cannot wear the following conventional lenses (polymethacrylate methi/I/) left eye visual acuity 0.02 (1,OX5-5.00) right fl
When the u I power 0.02 (1, OX5-5.00) was worn as power -500, it could be worn for 8 hours. Also, visual acuity is 1.1 in both eyes. o was produced.

After wearing this contact lens for one year, the base color
When I measured the power, there was no change.

The contact lenses used were as follows.

Right eye 765 k -5,008,8 k Example 7 The polymerization product complex 100 of DEAE dequinutran and sodium methacrylate obtained in Example 1 was fed into the mold of a molding machine at I7, l Q t /an''. Compress under vacuum to obtain tablets.

ACD blood 01 soap was placed on the surface, 0.01 tttl of 01M calcium chloride was added, and a coagulation reaction was caused on a watch glass in a 37°C hot water bath for 8 minutes, after which the amount of formed thrombus was measured.

The test was also performed on a glass surface under the same conditions for comparison, and the amount of thrombus generated was taken as 100%.

Results Glass surface: 100% Sample surface: 70% From the above, the polymerization product complex of DEAE dextran and sodium methacrylate has good anticoagulant ability.

[C@Loa0-(OH)-a・(OX　)a, lx　・H-0(1) [In the formula, X is -(CH=　)nRI(R1 is -NH2, -N(CH,)・, -N (C,H,)・, -N+(C2H,)s, -c, H4・NH*, -co・O,H,・N　H2, n=l~ 3 integer), or -〇OR, (R, is -CI-1, .NH, or -C, H, .Nu,) or -OH, CH(OH), OH, R, (Rs is -NH ,, -N (OH,), -N (0, H,), i -N + (C, H6)), a positive number of 0<a≦8, X≧5 integer]

The general formula of the unsaturated acid polymer represented by the formula (1) is represented by the T formula. (Here, ■ is a positive integer representing the C=CC bond of an unsaturated acid.) It is represented by the general formula (3) consisting of formulas (1) and (2). Matrix polymer according to claims 1 and 3. (9) The following formula (4) represents an aminoalkyl group of C1 to C, a dialkylaminoalkyl group of C, -C, a glycidyl group, a 'tetrahydrofuran group, a lower alkyl-substituted tetrahydrofuran group of 01 to C4, benzy, / L/ group and (-CH,CH,-0
-)yCCOOH,OH group (yFi is a positive number from 1 to 10), -N(,,R,,), (R,, is a hydrogen atom or O
, -04 alkyenyl group, pyridine group, tolyl group, and pyrrolidone group]. n is a polymer of an olefin compound represented by a positive integer from 20 to a o o, o o o. A copolymer of the matrix polymer according to claims 2 and 4 and another vinyl monomer, which is the formula (8) according to claim 8 and the formula (4). Voluntary amendment procedure Amendment Written April 23, 1985 Patent Application No. 12588 21. , Name of the invention: Matrix polymer and its manufacturing method and use 3, Person making the amendment, Relationship to the case Patent applicant address: 44-89 Kozora-cho, Seto City, Aichi Prefecture, Claims of the specification to be amended column and a column for detailed description of the invention. (2) 1 vinyl compound listed on page 4, item 17 of the specification
It is corrected as ``refined compound''. (3) Correct [vinyl compound-1] on page 8, line 20 to [olefin compound 1]. (4) "1-vinyl polymer" on page 9, line 11 is corrected to "1-year old reflex polymer." (5) "1-vinyl polymer" on page 9, line 12 is corrected to "1-year old reflex polymer." (6) "1-vinyl compound" on page 9, line 14 is corrected to "olefin compound." (7) "[Vinyl alcohol] on page 11, lines 9-10, 1 vinyl alcohol." (8) “Vinyl alcohol” on page 11, line 18.
is corrected to 1 vinyl alcohol. (9) “Vinyl alcohol” on page 11, line 14
is corrected to 1 vinyl alcohol. 2. Claims (1) Matrix polymer formed by polymerizing a cationic derivative of dextran with an unsolvable acid (2) Matrix polymer formed by polymerizing a cationic derivative of dextran with an unsolvable acid copolymer with other olefin monomers (3) A molded product of a matrix polymer obtained by polymerizing a cationic derivative of dextran with an unsaturated acid (4) A copolymer with a cationic derivative of dextran and an unsaturated acid. Molded product (5) comprising a matrix polymer obtained by polymerizing sulfuric acid and a copolymer of other olefin monomers. The molded product is a contact lens. Molded product (6) as described in 3 above, the molded product is a contact lens. Molded product (7) as described in 4 above, characterized in that a cationic derivative of dextran in a basic form is dissolved and mixed in a fusogenic acid. Method for producing the matrix polymer described in 3 and 4 above (8) The formula of the unit of the cationic derivative of dextran is (C=H702COH)-a・(OX)a)x・H
-0(1) [wherein X is -(CH2)nR1 (R1 is -
NH2,-N (OR3)2. - N CC2H,)2
．． -N9C, H, Hal C6H1・NR2, -CO-C
5Ht・NH, a group selected from the group consisting of n=1~
(an integer of 3), or -CO (R, is -CR2.NH, or -QaHt.NH,) or -CH2CH(OH).C
H, B, , (R, is -NH,, -N (Cl-1,),
, -N(C・H・)・, −N+(C・H・)・), a positive number of 0<a≦3, an integer of X≧5] In formula (1), The general formula of the unfouled acid polymer is represented by the general formula (3) consisting of the following formula (positive integer) (1) and (2). 7 trisocnu polymer according to claims 1 and 3. (9) The following formula (4) represents hydrogen, c, an alkyl group of ~012, cyclohexyl X, a hydroxyalkyl group of C, ~C1, CI''C
a aminoalkyl group, C+ to C, sialgylaminoalkyl group, chrycidyl group t tetrahydrofuran group, C
, -C, lower alkyl-substituted tetrahydronerane group, benzyl group and (C■=OH-0)yCH2C! H2O
II group (y is a positive number from 1 to 1O), -N(R,,)
, l & o are hydrogen atoms or a, -C, alkyenyl groups,
Indicates a pyridine group, tolyl group, and pyrrolidone group]. n is a polymer of an olefin compound represented by a positive integer from 20 to aoo or ooo. A copolymer of the matrix polymer according to claims 2 and 4 and another olefin monomer, which is composed of formula (8) according to claim 8 and this formula (4). 6-

Claims (1)

[Scope of Claims] (1) Matrix polymer obtained by polymerizing a cationic derivative of dextran with an unsoluable acid (2) Matrix polymer obtained by polymerizing a cationic derivative of dextran with an unsolvable acid copolymer with other vinyl monomers (8) A molded product of a matrix polymer obtained by bulk polymerizing a cationic derivative of dextran with an unfouled acid (4) Molded product (5) comprising a bulk copolymer of a matrix polymer obtained by polymerizing hydrochloric acid and another vinyl monomer. The molded product is a contact lens. Molded product (6) w The molded product is a contact lens. Molded product 1-(7) The molded product described in 4 above is characterized in that a base form of a cationic derivative of dextran is dissolved in fusogenic acid and subjected to bulk polymerization. Method for producing the matrix polymer described in 3 and 4 above (8) The formula of the unit of the cationic derivative of dextran is (C61(702(OH)3-a(OX)a)x (1
) [In the formula, X is -(CHz)n R1 (R1 is -NI(
2, -N(CHa)-. -N (C・old・, -dependent C・ru)・, −C,H,・corner,
-co・C! J(, .NI(, a group selected from the group consisting of, an integer of rows 1 to 3), or -COl(R, is -C
Tb-0 or -C@H, ・N1Tj) or -CI (20
I((OH) -CI-h Ra (几S is a pigeon. -N(OHjun., -N(C・H・n・, -N(C,
A group selected from the group consisting of H,)), 0<a≦3, an integer of shown. 2- (Here, L is the unsaturated acid's C=C bond.': C'
+s organic radical. n is 20 to aoo, oo. positive integer) The matrix polymer according to claims 1 and 3. (9) The following formula (4) is hydrogen, C+-CI aminoalkyl group, 01 to C8
dialkylaminoalkyl group, glycidyl group, tetrahydrofuran group, c, to C4 lower alkyl-substituted tetrahydrofuran group. Benzyl group and (-CHj(3几-o-)ycylC ratio O
H group (y is a positive number of 1 to 10), -N (R1=
) = (, R,, is a hydrogen atom or an alkyl group of 01 to C4. (R,, idC, to, an alkyl group of Ca), a phenyl group. Indicates a pyridine group, a tolyl group, a pyrrolidone group]. ■1 is a polymerization group of an olefin compound represented by a positive integer from 20 to aoo, ooo. Formula (3) described in claim 8 and this formula (4)"
A copolymer of the matrix polymer according to claims 2 and 4 and another vinyl monomer. ′