JPS58113102A - Method for slowing release of drug - Google Patents

Abstract

PURPOSE:To control the release of a drug, with little loss of the drug, by mixing a drug-containing granular carrier with a resin, and curing the mixture. CONSTITUTION:A drug (e.g. insecticide, synergist, repellent, vermin repellent, fungicide, etc.) is supported on a granular carrier (e.g. silica, kaolin, wood flour, etc.) and mixed homogeneously with a resin (e.g. nitrocellulose, epoxy resin, polyester resin, etc.), and the mixture is cured to control the release of the drug. By the proper selection of the amounts of the carrier and resin, the blooming can be prevented, and the dissipation of the drug can be controlled extremely effectively. The amount of the resin is 0.1-50pts.wt. per 1pt.wt. of the carrier. The slow-release composition obtained by the above mixing and curing process is used as a slow-releasing material in combination with a supporting substrate (e.g. a plastic sheet such as polyethylene sheet).

Description

DETAILED DESCRIPTION OF THE INVENTION 1- The invention relates to a method for sustained release of drugs, a sustained release composition, and a sustained release material. More specifically, it is characterized in that the release of the drug is controlled by mixing the powder adsorbed with the drug and sesame oil and hardening the mixture.

Conventionally, it has been known to mix a drug into a resin to achieve sustained release of the drug, and the degree of sustained release of the drug is determined by the resin φ used, so it is possible to control the release of the drug as desired. There are many things I can't do. In addition, the phenomenon of plumping, in which the chemical agent is pushed out during curing, is likely to occur, and chemical loss, wetting, and plumping have fatal drawbacks in terms of safety during use and the impact on the substrate. Therefore, in view of the current situation, the inventors of the present invention have conducted intensive research to develop a sustained release method that can prevent drug loss and appropriately control drug volatilization, resulting in the present invention. Ta.

That is, the present invention has 1. 1. A method for sustained release of a drug, which comprises controlling the release of the drug by mixing a powdery carrier holding the drug with a resin and curing the mixture. 2
．． 2. The method according to claim 1, wherein the drug is one or more of insecticides, synergists, repellents, insect repellents, repellents, fragrances, and deodorants. 8. 1. A sustained release composition for a drug, characterized in that a particulate carrier holding an M agent is mixed with a resin, and the mixture is cured.

4. Mixing the powdered carrier holding the drug and the resin,
The present invention relates to a material for sustained release of drugs, characterized in that the cured sustained release composition is held on a base material.

Based on the above-described structure, the present invention is capable of adjusting the amount of powder/granular carrier that holds the drug or the amount of resin that mixes the powder/granular carrier that holds the drug.
- It has the characteristics of preventing chemical compounding and controlling volatilization of the drug very effectively depending on the intended purpose.

Non-invention 1. The powder/granular carrier holding the drug to be used can be used by a dry method in which the drug is directly added to the powder/granular carrier and mixed, or by mixing the drug dissolved in a solvent with the powder/granular carrier and then stirring. It can also be prepared by a wet method in which the solvent is distilled off and dried.

In this case, the mixing ratio of the drug and the powder/granular carrier can be set arbitrarily, but the ratio of the drug to 1 part of the powder/granular carrier is 0.0 part.
1 to 5 parts by weight, preferably 0.05 to 2 parts by weight, is uniformly maintained to obtain a powder/granular material using the non-inventive powder.

The powder/granular carrier used in the present invention may be any carrier that can hold the drug and turn it into powder/granules (typical examples include silicic acid, kaolin, activated carbon, bentonite, diatomaceous earth, talc, clay, Examples include various mineral powders such as calcium carbonate, carbon black, and ceramic powder, various vegetable powders such as wood flour, soybean flour, wheat flour, and starch, and clathrate compounds such as IJn8-. It can be used alone or in a mixture of two or more.

The particle size of the above-mentioned powder/granular carrier when mixed with a-ifl is usually 10 to 600 μm, preferably 10 to ioomμ.

Mix the powder/granular carrier that retains the drug used in the present invention! Examples of fats include the following:

Cellulose derivative Toshitehanitrose V loose, Acetyl 7
Rate ttW loin, acetylbutyrylsenulose, methylcellulose, ethylse! Relose, acetylpropionyl cellulose, benzyl cellulose, hydroxypropyl se-Rhone, phosphorylated se-7 relose, etc., vinyl 1
VdR resins include polyvinyl alcohol, polyvinyl acetate, polyvinyl chloride, vinyl acetate, vinyl chloride copolymer, polyvinyl aceter M1 polyvinyl butyral, polystyrene, polymethyl acrylate resin, etc., alkyd resins such as 4-theta, chrycerin penta Acid-curing urea resins include urea or urea with a low degree of etherification; Examples of epoxy resins such as melamine cocondensation resins include halogenated bisphenol type resorcinol type, bisphenol F type, tetrahydrophenyl ethane type, novolac type, and boria l.
Ref-polyglycol type, glycerin triether type, polyolefin type, epoxidized soybean oil, or epoxy resin amine, etc., and diethylene triamine, triethylene tetramine, m-phenylene diamine, diaminocyphenylene, etc. are available as necessary. Amine ax hardeners such as Mhonpolyamide or organic acid anhydride hardeners such as phthalic anhydride, hexahydrophthalic anhydride, pyromellitic anhydride, maleic anhydride mixtures can be used.

Polyester resins include unsaturated dibasic acids such as maleic anhydride and fumaric acid, saturated dibasic acids such as adipic acid, phthalic anhydride, isophthalic acid, and tetrachlorophthalic anhydride, ethylene glyco-1, propylene glyco -7 and
1.8-butylene glycol, diethylene glycol,
Schif'robilene glycol, neopentyphreglyco-I
There are polyester resins made by condensation reaction with dihydric alcohols such as urethane resins, and urethane resins are resins with urethane bonds that are made of isocyanates and polyol-A/bacteria, which have at least two hydroxyl groups at the end of the molecule. It is a reactant, and the isocyanates include hexamethylene diisocyanate, naphthalene-1,5-diisocyanate, 4
．． 4'-diphenylmethane diisocyanates, polymers of the above diisocyanates, reaction products of the above diisocyanates and trimethylolpropane, etc. Polyol-Vs include ethylene glycol, prohylene glycol, butylene glycol (1,3-butanedio- M), 1.2
．． 6-hexane trio-7, trimethylolpropane, glycerin, soybean? Polyvalent Flucov such as Levitau V,
Melliates, which are polymers of the polyhydric alcohols mentioned above, polyester polyols or acrylic polyols, which are the reaction products of the polyhydric encores and their polymers with dibasic organic acids, or the above polyester polyols, etc., are mixed with coconut oil or castor. There are alkyd polyols modified with oil.

Examples of polysaccharides include vegetable gums such as gum arabic, chitin,
Proteins include xatone, pectin, starch, inulin, etc., and proteins include gelatin, casein, peptone, AI repmin, etc.

Natural resins include sumac, canny, and rosin (
1) Before. , a,)74-ya, e7. Ya7ag1. . -2
, diethylene glycol, esters such as glycerin, rosin derivatives such as 7-hydrogenated rosin, dehydrogenated rosin, polymerized rosin, amber, copal, cowri gum, dammer,
Examples include mastic, sandarac, shellac, oleo resin, and the like.

The drugs used in the present invention are not particularly limited, but the following may be exemplified.

Insecticides include pyrethrin, allethrin, phthalthrin, resmethrin, permethrin, finvalerate, phenothrin, flamethrin, cypermethrin, cyphenothrin, 1-ethiniA/-2-methyl-2-pentenyl-2,2-dimethytv-3-(2' Hyrethroid insecticides such as -methyv-1'-propenyl]-cyclopropane-1-poxylate (hereinafter referred to as MA), DDV
Organophosphorus insecticides such as P, diazinon, fenitrothion, marathon, dibrome, carbamate insecticides such as propoxa-, sevin, etc. Synergists include S-9-8-421, Viperoni I Leptoxide, Cinepirin 22
2. Cynevirin 500, piperonal dimethyl acetal, etc. are used as repellents, but N-diethyl-m-toluamide,
Butylacetanilide, ethyl theta hexanediol, butyl? Lepidroxyanisole, pt-butyl-m-cresol, etc. are used as insect repellents, naphthalene, camphor, valajichlorobenzene, etc., and as quadricidal agents, benzoic acids, sorbic acids, etc.
PCMX, BCA, thiophanate, triazine, Irgasan DP800, H/K f*-l, TBZl
f: x = Narrow I with fragrance, deodorant, geraniol, cinnamon alcohol, anethole, citral, citronellal, cinnamon alcohol, lilyal, limonene, vanillin, munu ketone, cineole, lauri? Examples include phosphoric acid methacrylate.

One or more of these drugs can be used in any combination depending on the purpose.

The mixing ratio of the powder/granular carrier holding the drug used in the present invention and #fat can be arbitrarily selected, but preferably 0.1 part by weight of the resin is mixed with 1 part by weight of the powder/granular carrier holding the drug.
The composition of the present invention is obtained by uniformly mixing up to 50 parts by weight, shaping it into the desired shape, and curing it.

The present invention also provides a sustained release material in which the above sustained release composition is held on a base material. The sustained-release material is used as a sheet base material, a V-piece member, etc., which has medicinal effects such as pest repellency by utilizing the characteristics of the base material.

Here, examples of the base material include synthetic resin sheets such as polyethylene, -Jzopropylene, nylon, polyvinyl chloride, polyvinylidene chloride, and polyester, animal and vegetable materials, or inorganic fiber sheets (paper, cloth, nonwoven fabric, mixed sheets or blended fabrics of synthetic resins and inorganic fibers or powders, blended fabrics or nonwoven fabrics of the above synthetic resins and animal and plant fibers, foils of metals such as aluminum, stainless steel, zinc, etc. Examples include films and laminated sheets of the various sheets mentioned above. Furthermore, as clay nail material, it can also be used effectively for furniture parts, such as natural wood such as awl, pencil fern, oak, etc., and molded products of plastics such as vinyl chloride, chlorinated polyethylene, polyethylene, polypropylene, etc. Available.

There are no particular limitations on the means for retaining the sustained-release composition of the present invention on the substrate, for example, by coating, impregnating, dropping, kneading, etc. It can be used by placing it on a spot or pasting it together.

There is no particular limit to the amount retained, and it may be determined as appropriate, or it may be retained up to approximately one times the amount of the saturated impregnated layer such as Motogetsu.

The drugs treated in this way are Kurisai 11 and Inactive 11.
- By changing the mixing ratio with the carrier, the desired sustained release property can be obtained, and the product can be put to practical use depending on the purpose and period of use of the drug.

The present invention will be specifically explained below using examples.

Example 1゜Resin fζ shown in Table 4S1 below was added and mixed with an inert carrier on which a drug was adsorbed, and 72g/H of high-quality paper (12X
After coating an amount equivalent to 609/Q on a 17 cm long film, the mixture was dried and cured at 100° C. for 5 minutes to obtain a sustained release material of the present invention in the form of a sheet.

Test Example 1 Using the treated sheet of Example 1 and a sheet treated to contain only the same amount of drug and resin, the sustained release effects were compared by analyzing the remaining amount of the drug over time.

Example 2゜α-olefin resin emulsion (solid content 4.9%,
Aikanigyo Co., Ltd.) 57 parts, ionomer (shunshi emulsion (solid content 50%, Asahi Dow Industries Co., Ltd.) 1
To 70 parts of the mixed resin emulsion made into 3 parts, 30 parts of a powder made by adsorbing 1 part of MA to 4 parts of silica gel (average particle size 200 mesh, manufactured by Fuji Tevison Co., Ltd.) was added and mixed, and 72'i/ 60 g/771 on high-quality paper
After applying a corresponding amount, the material was dried and cured at 100C for 2 minutes to obtain the sustained release material of the present invention in the form of an insect repellent sheet. 12 sheets of this
The product was cut into X17αF and used as a sheet insect repellent.

Test Example 2 An efficacy test of the sheet insect repellent shown in Example 2 was conducted. That is, using a 501-volume drawer containing clothes, three sheets of insect repellent were placed in the middle of the clothes, and then 20 35-day-old burr larvae and a 2 x 21 muslin cloth (approximately 5
Place a 60-mesh nylon bag containing 0q), close the lid, and leave in a dark place for 25'C. Two weeks after the larvae were placed, the number of larvae was counted to determine the mortality rate. Also,
For comparison, a sheet was used in which only the capsule agent was treated to be the same as the top paper.

Table 2 (as a blank, a drawer containing no drug was used and the larvae were placed between the clothes) Co., Ltd.) 0.8!i parts are uniformly mixed to form a powder. 1 part by weight of this powder and
SBR,! Backing agent (manufactured by Numata Chemical Products Co., Ltd.) 4
Hand-woven by uniformly mixing weight parts (15X15ff)
The mixture was coated in an amount equivalent to 1.4 kglrl, laminated with jute, and dried (100° C. for 80 minutes) to obtain a non-inventive sustained release material in the form of an insect repellent carpet.

Test Example 3 The efficacy of the insect repellent carpet shown in Example 3 was tested over time to compare the sustainability of the efficacy and confirm the sustained release effect.

That is, place one sugar cube whose weight has been measured in advance on the center of the insect-proof carpet, and place it in a container (40X 80X 25
Cm). (An untreated carpet with sugar cubes placed on it as a blank was placed next to the insect-proof carpet.) 100 adult German cockroaches were released into this container and left in a dark place at 25'C for 48 hours. After that, the residual life of the sugar cubes of the descendants was measured, the amount of reduction was calculated, and the repellency rate was determined using the following formula.

Reduced amount of sugar cubes on untreated carpet (repellent rate of 80% or more is considered to be practically effective).Also, for comparison, only the chemical used in Example 3 was treated with SB so that the same amount
A carpet prepared in the same manner as in Example 3 by adding and mixing it with the R child backing agent was used.

Example 4 87 g of β-cyclodextrin (0,0326 Aya 4) was dissolved in 2000 ml of distilled water, and the solution
TE A / 50 Hl Dissolve Seta D D V P 7
．． 29 (0,0826 mo, 41?) was added dropwise. During this time, the β-cyclodextrin solution was stirred with a magnetic stirrer, and a precipitate started to precipitate after about 1 drop of DDVP was added. After continuing stirring for 14 hours from this point, a white precipitate was collected by filtration using Toyo Roshi A5C. The white precipitate was mixed with 100g of acetone + ? , ether 1 0 0 wl
After washing with water and drying with a desiccator, a non-inventive sustained release composition in the form of a DDVP clathrate compound was obtained.

1 part by weight of this DDVP clathrate compound and vinyl acetate Emazion (solid content 50%, manufactured by Aikanigyo Co., Ltd.) were uniformly mixed, and 72g/10091n of the finished product was placed on high-quality paper.
After applying an amount equivalent to f, it was dried and cured at 100° C. for 5 minutes. This sheet was cut into 5×10 ffl pieces to obtain the sustained release material of the present invention in the form of an insecticidal sheet.

Test Example 4 Example 4F An efficacy test of the sheet insecticide shown above was conducted over time, the sustainability of the efficacy was compared, and the sustained release effect was confirmed.
Ta. That is, about 1. Using a pillow containing 7 kq, 8 sheet insecticides were placed inside the buckwheat husks, and over time a 60-mesh nylon bag containing 25 Kokunsutomotoki adults and fishmeal was placed inside the buckwheat husks, and the pillow Seal it in a polyethylene (80μ) bag and leave it in a dark place for 25 minutes. The number of deaths was counted 7 days after the installation of adult shorthorn beetles, and the mortality rate was determined. For comparison, sheets treated with the same amount of DDVP were used.

Table 4 Example 5. 1 part by weight of PCMX, 3 parts by weight of silica gel (20° mesh, manufactured by Fuji Davison Co., Ltd.) and 5 parts by weight of acetone were uniformly mixed, the acetone was evaporated with occasional stirring, and after drying. Obtain a powder.

To 1 part by weight of this powder, 4 parts by weight of vinyl acetate/acrylic copolymer Emma 7 Region (solid content 56%, manufactured by Aikanigyo Co., Ltd.) was mixed uniformly, and 72 g/100 q of high-quality paper was mixed. After coating an amount equivalent to 100 ml, it was dried and cured at 100'C for 5 minutes. A piece of paper with a bottom surface of 85 x 83 a was prepared from this sheet to obtain the sustained release material of the present invention in the form of a mildewproof sheet.

Test Example 5 The efficacy of the anti-mildew paper shown in Example 5 was tested over time to compare the sustainability of the efficacy and confirm the sustained release effect.

That is, a potato decoction was applied to a cotton cloth (5×5α),
After air-drying, the mixed spore suspension to be tested is spray inoculated. This cloth was placed in the middle layer of mold-proof paper containing 6 pieces of cotton cloth (82 x 80 LM), and then left in a Japanese dance room placed under 25C. The cotton cloth inoculated with the test spore suspension was placed in device 2.
After a week, they were taken out and incubated for 2 weeks in an incubator at a temperature of 28° C1 and a humidity of 95-99%, and the degree of mold growth was examined. The previous stock was Penicil
liumcitrinum AT CC98
49, Aspergillus oryzae
IFO28-4075, Chaetorniufflglobosu
Eight types of m ATCC6205 were used. For comparison, a piece of paper treated with the same amount of PCMX was used.

Table 5 degree of occurrence - No growth is observed at all.

Growth of 10 strands is observed below Z of cotton cloth.

Bacterial growth was observed on approximately 2% of the cotton fabric.

÷ Bacterial growth is observed over approximately % to the entire surface.

24-Example 6 1 part by weight of citral is uniformly mixed with 3 parts by weight of silicic anhydride (manufactured by Nippon Aerosil Co., Ltd.) to form a powder.

1 part by weight of this powder and vinylidene chloride ax emulsion (
4 parts by weight of solids content 47-49%, manufactured by Kureha Fhigaku Kogyo ■) were uniformly mixed, and 100 g of 120 Q/d high-quality paper was mixed.
The coating was coated with a paint equivalent to 100% and dried and cured (100'C, 5 minutes). This sheet was cut into a size of 20×30a to obtain a sustained release material of the present invention in the form of a fragrance plate.

Test Example 6 A sensory test of the fragrance plate shown in Example 6 was conducted over time to compare the persistence of the fragrance and confirm the sustained release effect.

That is, two fragrance plates were hung from the ceiling in a four-and-a-half tatami Japanese-style room, and the level of fragrance was sensually examined. For comparison,
A plate treated with only citral in the same amount was used.

Table 6 , 2 ’ 2 0 degree of aroma 0 No odor can be detected.

1. An extremely weak odor is observed.

2. An odor of normal strength is observed.

3. There is a strong odor.

(that's all) Patent applicant: Earth Seiraku Co., Ltd. 27- 16-

Claims (1)

[Scope of Claims] 1. A method for sustained release of a drug, which comprises controlling the release of the drug by mixing a powdery carrier holding the drug with a resin and curing the mixture. 2. Drugs or insecticides, synergists, repellents, insect repellents, fungicides,
The method according to claim 1, which is one or more of fragrances and deodorants. 3. A sustained release composition for a drug, which is characterized by mixing a powdery carrier holding a drug with a resin and curing the mixture. 4. A sustained release material for a drug, characterized in that the above sustained release composition obtained by mixing a powdery carrier holding a drug with a resin and curing the sustained release composition is held on a base material.