JPH0873691A - Polyvinyl alcohol hydrogel and method for producing the same - Google Patents

Abstract

(57) [Summary] [Structure] A polyvinyl alcohol hydrogel containing a sugar, wherein the sugar is a monosaccharide represented by the general formula: C _n H _2n O _n (wherein n is a positive integer), and A polyvinyl alcohol hydrogel which is at least one selected from the group consisting of reducing disaccharides represented by the general formula: C _{n + 1} H _2n O _n (where n is a positive integer). [Effect] This polyvinyl alcohol hydrogel effectively suppresses desorption of water and has excellent thermal stability and morphological stability, and is useful, for example, in the field of medical materials and the like.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a polyvinyl alcohol hydrogel which is useful in various applications including fields such as medical materials, and is particularly excellent in heat stability.
The present invention relates to a polyvinyl alcohol hydrogel with little water desorption in the air.

[0002]

2. Description of the Related Art Polyvinyl alcohol is a synthetic polymer having an affinity for water, and its hydrogel has been found by Nanbu et al. (JP-A-57-130543 and JP-A-58-36530). Polymer processing, 32 (11), 532
, 1983), temporary or long-term bio-substitutes (for example, "World of Poval", 111-199, published by Kobunshi Kogyokai).
2), application to various fields including the medical field such as contact lenses and phantoms for NMR diagnosis (JP-A-61-24744) has been proposed.
There is a problem that thermal stability and morphological stability are unsatisfactory.

As a method for improving the thermal stability of such polyvinyl alcohol hydrogel, (1) a method of repeatedly freezing and thawing an aqueous solution of polyvinyl alcohol or lyophilizing the aqueous solution, (2) a gel Using a mixed solvent such as water / dimethyl sulfoxide as a solvent for the polymerization, (3) using polyvinyl alcohol rich in syndiotactic as polyvinyl alcohol, (4) using polyvinyl alcohol with a crosslinking agent such as aldehyde A method of crosslinking and the like are generally known.

[0004]

However, the above method (1) has the drawbacks that the number of freeze / thaw cycles is large and that freeze-drying requires a long time.
The methods (4) and (4) have problems such as the use of an organic solvent which is not preferable from the viewpoint of safety and hygiene, and the complexity of the operation and the need to remove the organic solvent have been obstacles to commercial production. In addition, the method (3) has a drawback that it easily gels, but has a large volume change and is poor in economic efficiency, and further has a serious drawback that the desorption of water cannot be controlled. In the polyvinyl alcohol hydrogel obtained by the above method, the solvent (water) easily evaporates, the desorption of water from the gel cannot be controlled, the original gel state cannot be maintained, and the polyvinyl alcohol hydrogel of the above (1) and (2) According to the method, only a hydrogel having a melting point of at most about 70 ° C. could be obtained.

Therefore, an object of the present invention is to provide a polyvinyl alcohol hydrogel which is stable to heat and has excellent morphological stability in which water is hardly desorbed, and which has no safety and hygiene problems.

[0006]

According to the present invention invention the means for solving], a polyvinyl alcohol hydrogel containing a sugar, sugar, general formula: (wherein, n a positive integer) C _n H _2n O _n at Monosaccharide represented and a general formula: C _{n + 1} H _2n O _n (wherein n is a positive integer) At least one polyvinyl alcohol hydro selected from the group consisting of reducing disaccharides A gel is provided. Further, according to the present invention, there is provided a method for producing the above polyvinyl alcohol hydrogel, which has a step of preparing an aqueous solution containing polyvinyl alcohol and the above-mentioned sugar, heating the obtained solution to 100 ° C. or higher, and then rapidly cooling the solution. It

Polyvinyl alcohol Polyvinyl alcohol used as a main component of the hydrogel of the present invention is generally polyvinyl alcohol obtained by saponification of polyvinyl acetate, but is not limited thereto. For example, vinyl trifluoroacetate, vinyl formate, vinyl propionate, vinyl butyrate, vinyl pivalate, vinyl 2-ethylhexanoate,
Vinyl caprylate, vinyl caprate, vinyl laurate, vinyl myristate, vinyl palmitate, vinyl methacrylate, vinyl crotonate, vinyl sorbate,
Saponification of homopolymers of vinyl esters other than vinyl acetate such as vinyl benzoate, vinyl cinnamate, vinyl t-butyl benzoate and vinyl versatate, and copolymers of at least two of these vinyl esters and vinyl acetate. What was obtained by using it can also be used.

The average degree of polymerization of these polyvinyl alcohols (according to the method according to JIS K6726) is not particularly limited, but a range of 500 to 3000 is industrially general, and it is economically advantageous to select from this range. Is. The saponification degree of polyvinyl alcohol (according to the method based on JIS K6726) is preferably 98 mol% or more, but a completely saponified product is preferable, but it is not particularly limited and a range of 80 mol% or more is industrially general. It is economically advantageous to select from this range.

Further, modified polyvinyl alcohol, which is a copolymer of the above-mentioned polyvinyl alcohol and other monomers, can be used as long as the properties such as water solubility of the polyvinyl alcohol polymer are not impaired. Examples of such other monomers include unsaturated polycarboxylic acids or salts thereof, alkyl esters, complete alkyl esters, anhydrides, amides, imides, nitriles; unsaturated sulfonic acids or salts thereof; vinyl ethers; ethylene; vinyl chloride. At least one kind of α-olefin having 3 to 30 carbon atoms can be used. Such modified polyvinyl alcohol can be obtained, for example, by saponifying a copolymer of vinyl acetate and / or the above-mentioned vinyl ester other than vinyl acetate and the above-mentioned other monomer.

Sugar The sugar used in the present invention is a monosaccharide represented by the general formula (1): C _n H _2n O _n (where n is a positive integer) (1) and the general formula (2): C _{n + 1} H _2n O _n (where n is a positive integer) (2) is at least one selected from the group consisting of reducing disaccharides. Of the above sugars, glucose and fructose (both n = 6 in the general formula (1)) are preferable as the monosaccharide, and reducing disaccharides such as maltose are preferable as the reducing disaccharide. . Among them, maltose is suitable for obtaining a polyvinyl alcohol hydrogel excellent in morphological stability and heat stability, and fructose is suitable for obtaining a polyvinyl alcohol hydrogel particularly excellent in morphological stability. In the present invention, it is particularly preferable to use fructose and maltose. When a non-reducing disaccharide such as sucrose is used, a hydrogel having poor morphological stability is obtained, which is disadvantageous.

The concentration of sugar in the aqueous solution is generally 20 to 60.
It is preferably in the range of 50% by weight, particularly 50 to 60% by weight. If the sugar concentration is too low, it will be difficult to effectively suppress the desorption of water in the gel, and if the sugar concentration is too high, the solubility of polyvinyl alcohol will decrease, making it difficult to form a uniform hydrogel. There is.

Other Components In addition to the above-mentioned components, other components of the polyvinyl alcohol hydrogel of the present invention are known per se, for example, coloring components such as dyes and pigments; preservatives and bactericides. Preservatives such as; fragrances; plasticizing components such as glycerin and polyethylene glycol; inorganic fillers such as calcium carbonate and clay; organic fillers such as starch and corn starch; It can be added in combination. Of course, the amounts of these additives are appropriately set so that the physical properties of the hydrogel formed are not impaired.

Production of Gel The production method of the hydrogel of the present invention will be described in more detail. First, the above-mentioned aqueous solution of sugar is mixed with polyvinyl alcohol and, if necessary, the above-mentioned additives used, At least 100 ° C or higher, preferably 12
The polyvinyl alcohol is completely dissolved by heating to a temperature of 0 to 140 ° C. to prepare a uniform aqueous solution. This heating is
It is generally carried out under a pressure that does not cause boiling. To achieve complete dissolution of polyvinyl alcohol in a relatively short time, heating at 120 ° C or higher is preferable. However, if the temperature is too high, problems such as yellowing of the aqueous solution occur.

In the present invention, the polyvinyl alcohol concentration in this aqueous solution is usually preferably 3 to 12 g / dL, and more preferably 4 to 12 g / dL when the sugar is maltose. Generally, it is more advantageous to set the range of 5 to 7 g / dL because the dissolution and gelation can be performed in a relatively short time. If this concentration is too low, the time required for gelation becomes long. On the other hand, if the concentration is too high, the viscosity of the aqueous solution becomes high and the time required for dissolution becomes long.

After the dissolution by heating as described above, the obtained sugar-containing polyvinyl alcohol solution is rapidly cooled to gel. For example, gelation is performed by injecting a heated aqueous solution into a suitable mold and quenching continuously or batchwise. Of course, the above-mentioned heating may be performed in this mold. The degree of rapid cooling is generally appropriate in the range of 40 ° C./minute or more. Incidentally, such rapid cooling can be performed by an appropriate means such as using an appropriate refrigerant such as freon, liquid nitrogen, cold water, or storing the aqueous solution in a refrigerator, depending on the intended cooling temperature.

The cooling temperature is appropriately set to be lower than 100 ° C., specifically, -100 ° C. to 100 ° C. For example, in order to obtain a gel having high strength, it is preferable to cool to a temperature of 50 ° C. or lower. By heating at such a temperature and then rapidly cooling, a polyvinyl alcohol hydrogel which is stable to heat and has excellent morphological stability in which water is hardly released can be obtained. To obtain the polyvinyl alcohol hydrogel of the present invention, after dissolution by heating, 1) directly at −100 ° C.
After freezing to ~ -10 ° C, thaw (20-50 ° C),
A method of repeating the operation once or twice or more. 2) -10
There is a method of aging at 100 ° C. for 1 hour or more. Also in this case, after freezing at -10 ° C to -100 ° C, if necessary,
The operation of thawing at 20 to 50 ° C may be performed once or twice or more. Therefore, the cooling temperature can be appropriately selected from the methods 1) and 2). Generally, as the number of freeze / thaw cycles increases, the gel becomes more heat-stable, stronger and more morphologically stable.

[0017]

The hydrogel of the present invention is characterized in that an aqueous solution of the above-mentioned monosaccharide or reducing disaccharide is used as a gelling solvent for polyvinyl alcohol, thereby achieving the above-mentioned object of the invention. It was successful in doing. Although the mechanism is not always clear, in the hydrogel of the present invention, a large number of water molecules are associated with the sugar molecule, and therefore the desorption of water from the gel is suppressed,
It is presumed that it has both excellent thermal stability and morphological stability. These sugars easily dissolve in water,
It is a very safe and hygienic and inexpensive material.
Therefore, the hydrogel of the present invention is particularly useful for applications such as contact lenses, anti-adhesion agents for skin, artificial blood vessels, thrombosis, and medical purposes, and is extremely satisfactory commercially. Further, the hydrogel of the present invention can be produced without using a complicated operation, and since sugar is a substance which is easily dissolved in water and is an inexpensive substance, it is industrially extremely advantageous.

[0018]

【Example】

Example 1 Polyvinyl alcohol obtained by saponification of polyvinyl acetate (average degree of polymerization: 1300, degree of saponification: 99.9 mol%) was used to prepare an aqueous solution of various sugars (sugar concentration: 5).
0% by weight) or water (sugar concentration: 0% by weight), and then heated to 120 ° C. under pressure to prepare an aqueous sugar solution of polyvinyl alcohol. This aqueous solution is placed in a plastic container (inner diameter 2
9 mm, depth 50 mm), the mixture was rapidly cooled to -34 ° C and frozen at the temperature for 18 hours, and then thawed and thawed at room temperature for 6 hours. After repeating the freeze / thaw cycle three times, the compression elastic modulus of the hydrogel was measured using a thermomechanical analyzer (trade name: TMA4000, manufactured by Mac Science Co., Ltd.). That is, the measurement was performed while applying a constant vibration of 0.25 Hz to the gel at a load of 0.5 g while raising the temperature from 20 ° C. to 50 ° C. over 1.5 minutes. The obtained measurement result is 20
Since the measured values were almost the same in the range of ℃ to 50 ℃,
The compression elastic modulus (A) at about 25 ° C. was obtained. As an accelerated test for investigating desorption of water and sugar,
The compression elastic modulus (B) of the hydrogel subjected to the freeze-drying treatment after immersing the gel that had undergone the thawing cycle in water (room temperature, 3 days) was also measured. The compression modulus ratio (B / A) was obtained as an index of morphological stability, and the results are shown in Table 1.
Shown in

[0019]

[Table 1] A: Compressive elastic modulus of gel obtained by repeating freeze / thaw cycle three times B: Compressive elastic modulus of gel freeze-dried after immersing gel subjected to the above freeze / thaw cycle

From the above results, the hydrogel containing maltose or fructose only increased the compression elastic ratio to about 8 times even if the above-mentioned severe treatment was applied. In addition, the hydrogel containing sucrose has a compression elastic ratio of 35 times, and is significantly inferior in morphological stability to the reducing disaccharide. On the other hand, when sugar is not included, the compression elastic ratio is 1
It is understood that the water increases almost 00 times and the water is almost completely desorbed.

Example 2 The polyvinyl alcohol used in Example 1 was mixed with 50% by weight of a maltose aqueous solution so as to have a concentration of 4, 8 or 12 g / dL, and then heated to 120 ° C. under pressure to obtain polyvinyl. Four types of maltose aqueous solutions containing alcohol were prepared. Each aqueous solution was rapidly cooled, allowed to stand at 0 ° C. for 24 hours for gelation, and the melting point of the resulting hydrogel was measured by the following method. Table 2 shows the results. As is clear from Table 2, when a maltose aqueous solution containing polyvinyl alcohol at a concentration of 4 g / dL or more was used, the resulting hydrogel had a melting point in the range of 77 to 94 ° C and was very stable to heat. It was Further, the hydrogel obtained by allowing the gel to stand at 30 ° C. for 24 hours had the same melting point. The melting point of the sugar-free hydrogel prepared as a comparative example is 1
The melting point was 0 to 20 ° C., and the melting point increased only to about 70 ° C. even after repeating freeze and thaw eight times. The results are shown in Table 2.

Method for measuring melting point of hydrogel A part of the hydrogel is sampled in a sealed tube and 0.5 to 1 ° C. /
The temperature is raised at a rate of minutes and the temperature at which the gel begins to flow is taken as the melting point.

[0023]

[Table 2]

Example 3 The polyvinyl alcohol used in Example 1 was added at a concentration of 3,
After being mixed with a fructose aqueous solution (fructose concentration: 60% by weight) so as to be 4, 8 or 12 g / dL, the fructose aqueous solution of polyvinyl alcohol was prepared by heating to 120 ° C. under pressure. The aqueous solution was rapidly cooled and then left at 0 ° C. for 24 hours for gelation. When the melting point of the obtained hydrogel was measured in the same manner as above,
The results shown in Table 3 were obtained. As can be seen from Table 3, the melting point was very stable to heat in the range of 83.0 ° C to 95 ° C. Also, the melting point of the hydrogel gelled by leaving it at 10 ° C. for 24 hours is slightly lower than that at 0 ° C.
It was in the range of ° C.

[0025]

[Table 3]

Example 4 The polyvinyl alcohol used in Example 1 was prepared by changing the fructose aqueous solution or the sucrose aqueous solution (0, 20, 4) having various concentrations.
0, 60% by weight) to a concentration of 10 g / dL and then heated to 120 ° C. under pressure to prepare an aqueous solution of sugar containing polyvinyl alcohol. This aqueous solution was poured into a plastic container similar to that used in Example 1, and the temperature was -34 ° C.
After quenching for 18 hours and freezing for 18 hours at room temperature,
Thawed and thawed over time. The freeze / thaw cycle was repeated 3 times. Obtained hydrogel (initial gel)
After being weighed, it was left in the air and weighed periodically to measure water desorption. After 50 days, the weight of the hydrogel became almost constant (the gel thus obtained was called equilibrium gel). The results are shown in Table 4.

[0027]

[Table 4] (Note) ^{* 1} : Solvent retention indicates the amount of solvent (g) in the hydrogel per 1 g of polyvinyl alcohol, and is calculated by the following formula: (weight of equilibrium gel-weight of dry gel) / weight of dry gel. Value. ^{* 2} : The solvent retention rate (%) is a value calculated by the following formula: (weight of equilibrium gel / weight of initial gel) × 100.

From the above results, the higher the sugar concentration of the hydrogel, the higher the solvent retention, that is, the result that water is less likely to be desorbed. On the other hand, it is understood that water is almost completely eliminated when sugar is not contained. Further, by visual observation, the gel containing fructose showed the morphological stability by desorbing and reducing the solvent while maintaining the morphology at the initial stage of gelation.

[0029]

INDUSTRIAL APPLICABILITY The polyvinyl alcohol hydrogel of the present invention contains monosaccharides and / or reducing disaccharides, so that the elimination of water is effectively suppressed, and the thermal stability is maintained while the morphological stability is maintained. It is a well-balanced gel with excellent properties. Although this hydrogel is useful for various purposes, it is very effectively provided especially in the field of medical materials and the like.

Claims (5)

[Claims] 1. A polyvinyl alcohol hydrogel containing a sugar, wherein the sugar is a monosaccharide represented by the general formula: C _n H _2n O _n (wherein n is a positive integer) and the general formula: C _A polyvinyl alcohol hydrogel, which is at least one selected from the group consisting of reducing disaccharides represented by _{n + 1} H _2n O _n (where n is a positive integer). 2. The hydrogel according to claim 1, wherein the sugar is fructose or maltose. 3. The polyvinyl alcohol hydrogel according to claim 1, which has a step of preparing an aqueous solution containing polyvinyl alcohol and the sugar according to claim 1, heating the resulting solution to 100 ° C. or higher, and then rapidly cooling it. Manufacturing method. 4. The method for producing a polyvinyl alcohol hydrogel according to claim 3, wherein the sugar concentration of the aqueous solution is 20 to 60% by weight. 5. The method for producing a polyvinyl alcohol hydrogel according to claim 3, wherein the polyvinyl alcohol concentration of the aqueous solution is 3 to 12 g / dL.