JP3609898B2 - Water-soluble film for pharmaceutical packaging - Google Patents

Description

【００３０】
【発明の効果】
本発明の薬剤包装用水溶性フィルムは、ユニット包装用として優れた性能を有しており、水への溶解速度が速く、機械的強度およびタフネスに優れ、農薬や殺菌剤などの酸性物質や塩素含有物質を長期に渡って包装した場合であっても、水溶性の経時的な低下がない。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a water-soluble film for drug packaging such as acidic substances and chlorine-containing substances. More specifically, the present invention relates to a polyvinyl alcohol (hereinafter abbreviated as PVA) water-soluble film having excellent performance for packaging agricultural chemicals and fungicides.
[0002]
[Prior art]
In recent years, various chemicals such as agricultural chemicals are sealed and packaged in water-soluble films in unit quantities, put into water in their packaging form at the time of use, and the contents are dissolved or dispersed in water together with the packaging film. Many methods have been used. The advantages of this unit packaging are that it can be used without directly touching dangerous chemicals during use, and that a certain amount is packaged, so that weighing during use is unnecessary.
As the water-soluble film for unit packaging, a film made of unmodified partially saponified PVA is used. These water-soluble films are easily soluble in cold water and have excellent mechanical strength. However, chemicals such as acidic substances (pesticides) and chlorine-containing substances (bactericides and pesticides) are packaged and left for a long period of time. Then, the water solubility of the film decreased with time, and there was a problem that it became insoluble or hardly soluble in water.
[0003]
As a film for packaging an alkaline substance such as a detergent, a PVA film modified with a carboxyl group or a salt thereof is known, but when this PVA film is used for packaging an acidic substance or a chlorine-containing substance, There is a problem that the insolubilization of the film into water proceeds rapidly. In addition, attempts have been made to introduce an oxyalkylene group or a cationic group into PVA, but there has been a problem that the water solubility of the film is reduced during packaging.
[0004]
Currently, polyethylene oxide films and cellulose films are known as films for packaging acidic substances and chlorine-containing substances. However, these films have drawbacks such as a very slow dissolution rate in water, insufficient mechanical properties of the film, and extremely low impact resistance at low temperatures.
[0005]
[Problems to be solved by the invention]
The object of the present invention is to solve the above-mentioned problems, as a water-soluble film for drug packaging of acidic substances and chlorine-containing substances, etc., having excellent mechanical strength, flexible and tough film properties, and acidic for a long period of time. An object of the present invention is to provide a water-soluble film in which the water-solubility of the film is maintained even when a drug such as a substance or a chlorine-containing substance is packaged.
[0006]
[Means for Solving the Problems]
As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that 0.1 to 20 parts by weight of the reducing agent (B) and hydroquinone and hydroquinone monomethyl ether with respect to 100 parts by weight of the polyvinyl alcohol resin (A). And a water-soluble film for drug packaging formed by forming a composition containing 0.1 to 20 parts by weight of at least one radical scavenger (C) selected from the group consisting of p-tert-butylcatechol and the present invention. It came to complete.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
The PVA resin (A) used in the present invention is a saponified product of polyvinyl ester. A PVA-based resin is obtained by polymerizing vinyl ester in a solution using a solvent such as bulk or alcohol in the presence of a radical initiator and then partially or highly saponifying using an alkali or acid catalyst. It is done. Examples of the vinyl ester include vinyl acetate, vinyl propionate, vinyl formate, vinyl versatate, vinyl pivalate and the like, and industrially produced and cost-effective vinyl acetate is usually used.
[0008]
The PVA-based resin (A) used in the present invention may be modified PVA such as sulfonic acid group-containing modified PVA, carboxylic acid group-containing modified PVA, cation group-containing modified PVA, and alkylene oxide-containing modified PVA in addition to unmodified PVA. included. Among them, the sulfonic acid group-containing modified PVA is remarkably excellent in water-solubility of the film when it is packaged with an acidic substance or a chlorine-containing substance, has excellent chemical resistance, and does not deteriorate with time.
The monomer having a sulfonic acid group is not particularly limited as long as it contains a sulfonic acid group or a salt thereof in the molecule and can be copolymerized with a vinyl ester. Specific examples include 2-acrylamido-2-methylpropanesulfonic acid or an alkali metal salt thereof, 2-acrylamido-1-methylpropanesulfonic acid or an alkali metal salt thereof, and 2-methacrylamide-2-methylpropanesulfonic acid. Or the alkali metal salt etc. are mentioned. Among these, 2-acrylamido-2-methylpropanesulfonic acid or an alkali metal salt thereof is most preferable from the viewpoint of copolymerization reactivity with vinyl ester and stability during saponification. Further, olefin sulfonic acids such as ethylene sulfonic acid, allyl sulfonic acid, and methallyl sulfonic acid, or salts thereof may be used. Here, examples of the alkali metal salt include Na, K, and Li salts, and analogs such as ammonium salts and amine salts may be used. The case where the sulfonic acid group is in an acid state is also included in the present invention. However, since the sulfonic acid is a strong acid, it may cause problems such as hydrolysis of vinyl ester during copolymerization. It is desirable to be partially or completely neutralized with an alkali metal.
0.1-20 mol% is preferable, as for content of the copolymer unit which consists of a sulfonic acid group, 0.5-10 mol% is more preferable, and 1-5 mol% is especially preferable.
[0009]
The degree of polymerization of the PVA-based resin is required to have high strength and flexibility even when the film thickness is 10 to 100 μm. From the viewpoint of film strength and toughness, the viscosity average degree of polymerization (hereinafter abbreviated as polymerization degree) is required. ) Is preferably 300 to 10000, more preferably 500 to 8000. When the degree of polymerization is less than 300, the film strength becomes weak, and when the degree of polymerization is more than 10,000, the solution viscosity at the time of preparing the film becomes high and there is a problem in workability.
[0010]
The degree of saponification of the PVA-based resin is selected from the viewpoint of the water solubility of the film, the mechanical properties (strength, stiffness) of the film, and the bag-making property. In the case of unmodified PVA, 50 to 95 mol% is preferable, and 60 to 90 mol% is more preferable. In the case of the modified PVA, the range of the saponification degree may be wide because it becomes water-soluble even at a higher saponification degree. In the case of a sulfonic acid group-containing modified PVA, 40 to 100 mol% is preferable, 60 to 100 mol% is more preferable, and 70 to 99.5 mol% is particularly preferable.
[0011]
The reducing agent (B) used for this invention is a compound which has the effect | action which prevents the oxidation of PVA-type resin (A). Examples of the reducing agent include tartaric acid, ascorbic acid, sodium thiosulfate, sodium sulfite, Rongalite and the like. Of these, tartaric acid is particularly preferable. As a compounding quantity of a reducing agent, it is 0.1-20 weight part with respect to 100 weight part of PVA-type resin, 0.3-10 weight part is preferable, and 0.5-3 weight part is especially preferable. When the compounding amount of the reducing agent is less than 0.1, water solubility decreases when an acidic substance or a chlorine-containing substance is packaged. When the compounding amount of the reducing agent exceeds 20 parts by weight, the film strength is lowered or white powder is deposited on the film surface.
[0012]
The water-soluble film of the present invention is characterized by using a reducing agent (B) and a radical scavenger (C) in combination. The radical scavenger (C) used in the present invention is a compound having a function of capturing radicals generated during packaging and leaving them to stand and converting them into an inert substance . Specifically, hydroquinone, hydroquinone monomethyl ether, p- tert-Butyl catechol . As a compounding quantity of a radical scavenger, it is 0.1-20 weight part with respect to 100 weight part of PVA-type resin, 0.1-5 weight part is preferable, and 0.5-3 weight part is more preferable. When the blending amount of the radical scavenger exceeds 20 parts by weight, the film strength is reduced, powder is deposited on the film surface, or the film is colored.
[0013]
As a method for forming a film of the composition, any method such as casting of the aqueous solution or melt extrusion in the presence of a suitable plasticizer or water is used. At that time, usual additives such as a colorant, a fragrance, an extender, an antifoaming agent, a release agent, an ultraviolet absorber, an inorganic powder, and a surfactant may be appropriately blended as necessary. Moreover, you may add water-soluble polymers, such as normal PVA, starch, carboxymethylcellulose, methylcellulose, and hydroxymethylcellulose, as long as the characteristic of this invention is not impaired as needed.
[0014]
Since the water-soluble film of the present invention can be transported, stored and used even in a hot and humid region or a cold region, the strength and toughness of the film are required, and impact resistance at a low temperature is particularly required. Therefore, various plasticizers are used to lower the glass transition point of the film. Any plasticizer that is commonly used as a plasticizer for PVA can be used. Specific examples of plasticizers include polyhydric alcohols such as glycerin, diglycerin and diethylene glycol, polyethers such as polyethylene glycol and polypropylene glycol, phenol derivatives such as bisphenol A and bisphenol S, and N-methylpyrrolidone. This includes amide compounds, compounds obtained by adding ethylene oxide to polyhydric alcohols such as glycerin, pentaerythritol, and sorbitol, and water. The amount of plasticizer added varies depending on the type of PVA resin used and the type of acidic substance used, but it is 0 to 50 parts by weight, preferably 5 to 30 parts by weight per 100 parts by weight of PVA resin. is there.
[0015]
As the drug packaged in the water-soluble film of the present invention, an acidic substance or a chlorine-containing substance is preferable. The shape of the drug may be granular, tablet, powder, or liquid in some cases. Further, a developing agent such as talc, kaolin, bentonite, diatomaceous earth, or the like used as a carrier for the drug, a surfactant or a dispersant for improving the affinity to water and dispersibility are also included in the drug of the present invention.
[0016]
The acidic substance is a substance having a pH of 5 or less when made into a 1% by weight aqueous solution or aqueous dispersion, and includes various substances such as agricultural chemicals, bactericides, and deodorants. The solubility of the acidic substance in water may be completely dissolved or partially dissolved and dispersed, and the substance adsorbed on the inorganic powder may be in the form of a slurry in water.
[0017]
Examples of the chlorine-containing compound include agricultural chemicals containing chlorine in the molecule, bactericides, bleaches, and the like. Specifically, isocyanic acid trichloride, isocyanic acid dichloride, N, N-dichlorohydantoin, N-chloro-N. -Bromo-5,5-dimethylhydantoin, other agricultural chemicals (ECP, BHC) and the like.
The shape of the chlorine-containing substance may be granular, tablet, powder, or in some cases liquid.
[0018]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto. In the examples, “%” and “parts” are based on weight unless otherwise specified.
[0019]
[Method of measuring water solubility of film]
A film sample was cut into a 40 × 40 mm square, squeezed with a slide mount, immersed in water stirred at 20 ° C. and 10 ° C., and the time (seconds) until the film was completely dissolved was measured. .
[0020]
[Method for measuring pH of substance]
Non-powdered products such as granules and tablets were finely crushed in a mortar to form a powder, 1 g of this was weighed, placed in 99 g of distilled water, and stirred at room temperature for 30 minutes. The pH of this aqueous solution was measured with a pH meter.
[0021]
Example 1
To the methanol solution of the copolymer obtained by copolymerizing vinyl acetate and sodium 2-acrylamido-2-methylpropanesulfonate in a methanol solvent, a methanol solution of sodium hydroxide is added to carry out a saponification reaction by a conventional method. Then, a sulfonic acid group-containing PVA having a polymerization degree of 1650, a saponification degree of 88 mol%, and a content of 2 mol% of copolymer units composed of sulfonic acid groups was obtained. An aqueous solution is prepared using a composition in which 100 parts of this modified PVA is mixed with 1 part of tartaric acid as a reducing agent, 1 part of hydroquinone monomethyl ether as a radical scavenger and 20 parts of glycerin as a plasticizer, and cast into a heat roll at 70 ° C. Thus, a film having a thickness of 40 μm was obtained.
A 10 cm × 15 cm bag was made from this film, and 40 g of a fine powder of succinic acid as a reagent, which is an acidic substance, was put into a heat seal and sealed. The pH of this 1% aqueous solution of succinic acid was 2.4. This packaging bag was further heat sealed with a film of aluminum laminated on polyethylene and sealed and double-wrapped to prevent water and plasticizers from splashing from the packaging bag of the acidic substance. This bag was placed in a thermostat at 50 ° C. as an accelerated test for a long-term storage test, taken out after one month, and the change in water solubility of the packaged film over time was examined. The results are shown in Table 1. There was almost no decrease in water solubility after standing, and the film was good without coloration or a decrease in transparency.
[0022]
Example 2
It was left at 50 ° C. for 1 month in the same manner as in Example 1 except that 20 g of a tablet of isocyanuric acid trichloride (pH = 4.2) as a bactericide was packaged. After one month, the film was removed and the water-soluble change of the packaged film was examined. The results are shown in Table 1. There was almost no decrease in water solubility after standing, and the film was good without coloring or odor.
[0023]
Example 3
100 parts of unmodified PVA (polymerization degree 1750, saponification degree 88 mol%), 2 parts of ascorbic acid as a reducing agent, 0.5 parts of hydroquinone as a radical scavenger, 10 parts of glycerin as a plasticizer and 1 mole of sorbitol The mixture was allowed to stand at 50 ° C. for 1 month in the same manner as in Example 2 except that a film was prepared using a composition containing 15 parts of a compound having 2 moles of added. After one month, the film was removed and the water-soluble change of the packaged film was examined. The results are shown in Table 1. Although the water solubility after standing was somewhat lowered, it was completely dissolved without any dissolution residue, and was good without coloration of the film and a decrease in transparency.
[0024]
Comparative Example 1
At 50 ° C. in the same manner as in Example 1 except that a film was prepared using 100 parts of unmodified PVA (polymerization degree 1750, saponification degree 88 mol%) and 20 parts of glycerin as a plasticizer. Left for one month. After one month, the film was removed and the water-soluble change of the packaged film was examined. The results are shown in Table 1. The film after standing was colored brown and hardly swelled even when immersed in water.
[0025]
Comparative Example 2
Except that a film was prepared using a composition in which 100 parts of modified PVA used in Example 1 was blended with 10 parts of glycerin as a plasticizer and 15 parts of a compound obtained by adding 2 moles of ethylene oxide to 1 mole of sorbitol. In the same manner as in Example 2, it was left at 50 ° C. for 1 month. After one month, the film was removed and the water-soluble change of the packaged film was examined. The results are shown in Table 1. The film after standing was colored brown and hardly swelled even when immersed in water.
[0026]
Example 4
Maleic acid-modified PVA (polymerization degree 1280, saponification degree 96 mol%, degree of modification 4 mol%) in 100 parts, 3 parts of sodium thiosulfate as a reducing agent, p-ter t as the radical scavenger - butylcatechol 2 parts of plasticizer As in Example 2 except that a film was prepared using a composition containing 20 parts of glycerin. After one month, the film was removed and the water-soluble change of the packaged film was examined. The results are shown in Table 1.
[0027]
Example 5
In the same manner as in Example 1, sodium acrylamide-2-methylpropanesulfonate and vinyl acetate were copolymerized and subjected to a saponification reaction, and a copolymer having a polymerization degree of 1250, a saponification degree of 98 mol%, and a sulfonic acid group. A sulfonic acid group-containing PVA having a unit content of 4 mol% was obtained. This PVA100 parts, 1 part tartrate as a reducing agent, was blended with 1 part of Hydro quinone monomethyl ether and compound 15 parts obtained by adding ethylene oxide 2 moles relative Glycerin 10 parts of 1 mol of sorbitol as a plasticizer as the radical scavenger A film was prepared using the composition, and the same procedure as in Example 1 was performed except that a bactericidal agent (pH = 4.0) containing bromo, chloro-5,5-dimethylhydantoin and boric acid as a drug was packaged. It was left at 50 ° C. for 1 month. After one month, the film was removed and the water-soluble change of the packaged film was examined. The results are shown in Table 1. There was no decrease in water solubility after standing, and the film was good without coloring, decreased transparency and odor.
[0028]
Comparative Example 3
The film was allowed to stand at 50 ° C. for 1 month in the same manner as in Example 5 except that a film was prepared using a composition containing no reducing agent and radical scavenger. After one month, the film was removed and the water-soluble change of the packaged film was examined. The results are shown in Table 1. The film after standing was colored and insolubilized in water.
[0029]
[Table 1]

[0030]
【The invention's effect】
The water-soluble film for drug packaging of the present invention has excellent performance for unit packaging, has a high dissolution rate in water, is excellent in mechanical strength and toughness, contains acidic substances such as agricultural chemicals and bactericides, and contains chlorine. Even when the substance is packaged over a long period of time, there is no decrease in water solubility over time.

Claims (2)

0.1 to 20 parts by weight of the reducing agent (B) and at least one radical selected from the group consisting of hydroquinone, hydroquinone monomethyl ether and p-ter-butylcatechol with respect to 100 parts by weight of the polyvinyl alcohol resin (A). A water-soluble film for drug packaging formed by forming a composition containing 0.1 to 20 parts by weight of the scavenger (C) . The water-soluble film for drug packaging according to claim 1, wherein the polyvinyl alcohol resin (A) is a polyvinyl alcohol resin containing 0.1 to 20 mol% of a copolymer unit comprising a sulfonic acid group.