Biodegradable sustained-release preparation and biodegradable pheromone dispenser

Abstract: Described are a biodegradable sustained-release preparation which comprises a mixture of 99 to 10 parts by weight of an aliphatic polyester and 1 to 90 parts by weight of a modifier for the regulation of sustained releasability of an active ingredient, and the active ingredient held by said mixture; a biodegradable pheromone dispenser, wherein an aliphatic polyester is used as a sustained release layer for a pheromone contained therein as a liquid phase, said aliphatic polyester having recurring units whose ratio (I/II) of (I) the number of the carbon atoms constituting the main chain and not relating to ester linkage to (II) the number of the carbon atoms constituting the ester linkage is 2 or larger; and a biodegradable pest controlling agent which is obtained by mixing and dispersing an active ingredient and a carrier for holding said active ingredient in a biodegradable aliphatic polyester or which comprises 2 to 60 wt.% of an active ingredient, 30 to 95 wt.% of a biodegradable aliphatic polyester and 2 to 50 wt.% of a carrier for holding the active ingredient.

Description: The present invention relates to a biodegradable sustained-release preparation, and a biodegradable pheromone dispenser. A first group of this invention relates to a biodegradable sustained-release preparation. In recent years, sustained release of an active ingredient has attracted attentions in various fields. For example, there is an aromatic which imparts a refreshing smell to the air in a room which comprises as a pest controlling means, a mating disruption agent making use of a sex pheromone in combination with attracting insecticide. These agents are required to have stable effects for a long period of time so that an excellent technique for sustained release is necessary. Recently, they are desired to have biodegradability in addition. For example, a mating disruption agent, attracting insecticide or the like used for agricultural purposes is hardly collected after use and most of them are left alone in the upland field or the like. Because, collection of such an agent, which has been distributed in a large amount, after application requires many hands and is therefore substantially impossible. The aromatic used indoors is disposed as rubbish. Since plastic waste matters generate much heat at the time of incineration, thereby damaging an incinerator, they are often buried in the ground. Accordingly, there is a demand for a biodegradable type sustained-release preparation which can be degraded by microorganisms at the time when buried in the ground and does not remain in the soil. In recent years, various materials having biodegradability have been proposed and some of them have already been industrialized. They can be classified into some groups from the viewpoint of the raw material constituting them. Examples include cellulose type, starch-added type, aliphatic polyester type and polyvinyl alcohol type. They are used suitably in consideration of their characteristics such as applications or price, however, an aliphatic polyester type is preferred for the sustained release of an active ingredient. For the agricultural applications where an agent tends to be left alone in the field after application, described in Japanese Patent Application Laid-Open No. 6-116103 is a pest controlling agent comprising a biodegradable aliphatic polyester and an active ingredient. The present inventor has already developed, as a sustained-release pheromone preparation having biodegradability, a sustained-release pheromone preparation comprising as a sustained-release layer, a polymer composed mainly of 3-hydroxybutyric acid (Japanese Patent Application Laid-Open No. 5-163110). As described above, an aliphatic polyester type preparation is used preferably as a sustained-release preparation having biodegradability. In the aliphatic polyester, however, molecular chains are firmly bonded statically through an ester linkage in its structure, which makes it difficult for the active ingredient to diffuse the gap of the polymer segment, resulting in small transmittance of the active ingredient through the aliphatic polyester. The aliphatic polyester is therefore accompanied with the problem that a release surface area should be widened in order to increase the transpiration amount of the active ingredient or a number of sustained release preparations should be placed in order to secure a certain concentration. A second group of the present invention relates to a biodegradable pheromone dispenser. In recent years, as a pest controlling means, a controlling method making use of a pheromone has attracted attentions because it is safe and besides, it does not impart the pest insects with resistance. A pheromone dispenser is required to release a pheromone stably for a long period of time in order to deal with the breeding of pest insects over a breeding season and is also required to have applicability to crops or other things to be treated. Various pheromone dispensers equipped with both excellent release performance and easy applicability have therefore been proposed. The pheromone dispensers so far proposed can be classified into three types based on their shapes. The first one is a microcapsule or hollow fiber type used for distribution. The second one is a matrix type wherein a pheromone has been dispersed in a polymeric material. The third one is a so-called reservoir type in which a pheromone has been held as a liquid. The microcapsule or hollow fiber type can be applied easily by distribution or the like but involves a problem such as short control period. The matrix type is accompanied with the problem that the release rate of a pheromone depends on the pheromone concentration in the polymeric material so that the release rate inevitably shows a gradual decrease. Accordingly, as a pheromone dispenser, the reservoir type whose intra-membrane concentration gradient does not change so much has been rated high because of stable release performance over a long period of time. It is however the present situation that most of such pheromone dispensers are not collected after application to the field such as upland field and are left alone in the field. There has accordingly been a demand for a biodegradable type pheromone dispenser which is degraded in the soil and does not remain in the field and various proposals have already been made. For example, in Japanese Patent Application Laid-Open No. 6-116103, a pest controlling agent made of a biodegradable aliphatic polyester is described. Described are a spherical pest controlling agent wherein the surface of an active ingredient in the form of a microcapsule has been covered with a biodegradable polymeric material; a spherical-, film- or ribbon-shaped material obtained by dispersing an active ingredient in a biodegradable polymeric material and then forming or molding the resulting dispersion; a film-shaped material having a barrier layer on its surface; and an adhesive-layer-having agent permitting easy application. Also described in it is a method of encapsulating an active ingredient in a capillary-shaped tube and releasing an active ingredient from the opening portion of the capillary tube. It is however difficult to secure stable release over a long period of time by such pest controlling agents. As describe above, the present inventor has already proposed (Japanese Patent Application Laid-Open No. 5-163110) a sustained-release pheromone preparation using, as a sustained-release layer, a polymer composed mainly of 3-hydroxybutyric acid. Use of this polymer however requires a decrease in the thickness of the sustained-release layer or an increase in the release surface area, because this polymer has a small transmittance rate of a pheromone. As such, a polyester is a substance having a small transmittance of pheromones and is not suited for use as a material for a reservoir type pheromone dispenser. Described specifically, aromatic polyesters such as polyethylene terephthalate hardly transmits pheromones. Aliphatic polyesters are not always same in the transmittance of pheromones. Under such situations, the kind and thickness of the aliphatic polyester appropriate for a sustained-release layer of a reservoir type pheromone dispenser having both biodegradability and sustained release property of pheromones have not yet been made cleared. An object of the first group of the present invention is to provide a biodegradable sustained-release preparation which can, during application, carry out sustained release of its active ingredient stably at a desired release rate for a long period of time and after application, is degraded by microorganisms even buried in the ground and does not remain in the soil. According to an aspect of the first group of the present invention, there is thus provided a biodegradable sustained-release preparation as claimed in claim 1. An object of the second group of the present invention is to provide a reservoir type biodegradable pheromone dispenser which permits, during application, stable sustained release of a pheromone over a long period of time and after application, does not require collection work because of its biodegradability and therefore does not remain in the soil. Polyester features that an ester linkage in its structure firmly combines molecular chains through a static bond so that it is difficult for pheromone molecules to diffuse the gap of the polymer segment, resulting in a small transmittance of the pheromone in the polyester. The present inventor has found that releasability of a pheromone can be controlled by widening the gap between ester linkages of the main chain structure of an aliphatic polyester and completed the invention of the second group. According to an aspect of the second group of the present invention, there is thus provided a biodegradable pheromone dispenser as claimed in claim 7. FIG. 1 is a schematic view illustrating alternative embodiments of a tube-shaped dispenser among the dispensers according to the second group of the present invention; FIG. 2 is a perspective view illustrating alternative embodiments of a bag-shaped dispenser among the dispensers according to the second group of the present invention; FIG. 3 is a perspective view illustrating another embodiment of a bag-shaped dispenser among the dispensers according to the second group of the present invention. The invention is further described, by way of example only, with reference to the following examples. 1. Biodegradable sustained-release preparation (according to the first group of the invention) As a mixture for holding an active ingredient of the sustained-release preparation according to the first group of the present invention, employed is a mixture comprising 99 to 10 parts by weight of an aliphatic polyester and 1 to 99 parts by weight (when no other components are contained, the above weight part can be replaced by wt.%) of a modifier for regulating the releasability of the active ingredient held therein. When the amount of the modifier is smaller than 1 part by weight relative to 99 to 10 parts by weight of the aliphatic polyester, the modifier does not exhibit its effects. When the amount of the aliphatic polyester is smaller than 10 parts by weight relative to 1 to 90 parts by weight of the modifier, on the other hand, no biodegradation effects can be expected. The mixture for holding the active ingredient is more preferred to contain the modifier at a concentration falling within a range of from 5 to 60 wt.%. No particular limitation is imposed on the above-described aliphatic polyester insofar as it has biodegradability. Specific examples include condensation and polymerization products between a C 2-20 carboxylic acid such as malonic acid, succinic acid, succinic anhydride, glutaric acid, adipic acid, adipic anhydride, sebacic acid, fumaric acid, maleic acid, didodecanoic acid, malic acid, tartaric acid or citric acid and a C 2-20 alcohol such as ethylene glycol, propylene glycol, butane diol, hexane diol, octane diol, decane diol, cyclohexane dimethanol, glycerin, or trimethylol propane; ring-opening polymerization products of a cyclic ester such as lactide, which is a cyclic dimer of lactic acid, or caprolactone; condensation and polymerization products of a hydroxy acid such as lactic acid, hydroxybutyric acid or hydroxyvaleric acid. The above exemplified aliphatic polyesters can be used either singly or in combination. As a modifier for regulating the sustained releasability of an active ingredient, any modifiers having an equilibrium swelling ratio at 40°C of at least 2 wt.% can be used. The term "equilibrium swelling ratio" as used herein means an equilibrium swelling ratio at 40°C represented by the following formula: Equilibrium swelling ratio = (Weight of swelling sample - Weight of dry sample) Weight of dry sample x 10 Examples of such a modifier include natural high polymers such as cellulose, chitin, chitosan, pullulan and polyamino acid, and derivatives thereof; and synthetic high polymers such as polyvinyl alcohol, polyethylene glycol, polyurethane, polyamide and polyolefins, e.g. polyethylene, polypropylene and polystyrene, and derivatives thereof. From the viewpoint of the miscibility with an aliphatic polyester and modifying effects of the sustained releasability of an active ingredient, desired are poly-ε-caprolactone, polyvinyl acetate, ethylene-vinyl acetate copolymer, ethylene-ethyl acrylate copolymer, polyvinyl chloride, polymethacrylate ester and cellulose derivatives such as cellulose triacetate and cellulose acetate butyrate, and mixtures thereof. Concerning the ethylene-vinyl acetate copolymer, that having a vinyl acetate content of 4 to 90% is suitably used. Any substance having physiological activities such as attracting activity, repellent activity and aromatic activity and pesticidal activities such as insecticidal activity can be employed as the active ingredient of the first group of the present invention without particular limitation. Specific examples of the active ingredient having attracting activity include Z-7-dodecenyl acetate, Z-8-dodecenyl acetate, Z-9-dodecenyl acetate, E,Z-7,9-dodecadienyl acetate, Z,Z-7,9-dodecadienyl acetate, E,E-8,10-dodecadienol, E-4-tridecenyl acetate, Z-9-tetradecenyl acetate, Z-9-tetradecenal, Z-11-tetradecenyl acetate, Z-11-tetradecenal, Z-9-hexadecenal, Z-11-hexadecenal, Z,E-9,11-tetradecadienyl acetate, Z,E-9,12-tetradecadienyl acetate, Z-11-hexadecenyl acetate, Z,Z-7,11-hexadecadienyl acetate, Z, E-7,11-hexadecadienyl acetate, E,E,Z-4, 6,10-hexadecatrienyl acetate, E,E-10,12-hexadecadienal, Z,Z-3,13-octadecadienyl acetate, E,Z-3,13-octadecadienyl acetate, Z-7,8-epoxy-2-methyl-octadecene, Z-13-icosen-10-on, E,E,Z-10,12,14-hexadecatrienyl acetate, E,E,Z-10,12,14-hexadecatrienal, Z-10-tetradecenyl acetate, E,Z-4,10-tetradecadienyl acetate, 14-methyl-1-octadecene, (R,Z)-5-(1-octenyl)oxacyclopentan-2-on, (R,Z)-5-(1-decenyl)oxacyclopentan-2-on and (R,Z)-5-(1-decenyl)oxacyclopentan-2-on. These compounds are known as pheromones and are composed of a C 10-20 unsaturated aliphatic hydrocarbon, acetate, aldehyde, alcohol, ketone or epoxy compound. They can be used either singly or in combination. Examples of the active ingredient having repellent activity include triethylene glycol monohexyl ether and N,N-diethyl-m-triamide. Examples of the active ingredient having aromatic activity include geraniol, limonene, benzyl alcohol, esters of a C 6-20 hydrocarbon, ethers, aldehydes and alcoholic compounds. Examples of the active ingredient having pesticidal activity include insecticides such as salithion, diazinon and chlorpyrifos and bactericides such as thiophanate-methyl and captan. The container formed of a holding mixture which container has an active ingredient enclosed therein as a liquid phase is more preferred in order to secure uniform releasability over a long period of time. As such shape, tube-, bottle- or bag-shaped container is used. The active ingredient hold as a liquid phase in such a container transmits through a sustained-release layer constituting the preparation, thereby being released. When the holding mixture is formed into a container and the active ingredient is enclosed therein, the sustained release layer means the wall of the container itself. When the mixture is formed into a container, the sustained release layer desirably has a thickness of at least 0.02 mm for effecting stable sustained release. The thickness smaller than 0.02 mm is not preferred because it causes pinholes or excess release of the active ingredient such as pheromone. There occurs no particular problem when the sustained release layer has a thickness not smaller than 0.02 mm, but that ranging from 0.05 mm to 5 mm is more preferred. When it exceeds 5 mm, the release amount of a pheromone tends to become too small. The release surface area of the sustained release preparation formed of such a container is desirably 1 cm 2 or larger. Surface areas smaller than 1 cm 2 make it difficult to secure a sufficient release amount and are therefore not suited. No particular problem occur when the release surface area is 1 cm 2 or larger, but a range of from 2 cm 2 to 2 m 2 is more preferred. Surface areas exceeding 2 m 2 are not practical because it is difficult to install the preparation having such a large surface area. When the active ingredient is enclosed and held in a container of the sustained release preparation, said container having been formed of a holding mixture, it may be enclosed in portions. The enclosed amount is preferably at least 1 mg, more preferably at least 5 mg. It is difficult to enclose the ingredient in an amount less than 1 mg. As the shape of the container formed of a holding mixture, a tube, bottle and bag are necessary. In the case of the tube-shaped preparation, that having an internal diameter of 0.4 mm to 10 mm is preferred. Internal diameters smaller than 0.4 mm make it difficult to fill the active ingredient in the container, while those larger than 10 mm make it difficult to conduct encapsulation. The bottle-shaped preparation is formed by blow molding or injection molding and preferred is that having an internal volume of 0.1 to 200 ml. The bottle having an internal volume less than 0.1 ml cannot be formed easily, while that having an internal volume greater than 200 ml is not economical because there is a large difference between the amount of the active ingredient filled therein and the internal volume. In the case of a bag-shaped preparation, the amount of the active ingredient filled in the bag is desirably 1 mg to 100 g. Neither amounts smaller than 1 mg nor exceeding 200 g are preferred because it is difficult to fill such an amount in the bag. The biodegradable sustained-release preparation according to the first group of the present invention should retain its essential performance during application so that a pigment or dye, or various stabilizers such as ultraviolet absorber or antioxidant may be added to the holding mixture in order to improve the weather resistance. Alternatively, it is possible to add such an additive to the active ingredient enclosed in the container formed of a holding mixture. Examples of the first group of the present invention will hereinafter be given but it should however be borne in mind that the fist group of the present invention is not limited to or by these examples. Example 1 In a twin roll, a polycondensate (product of Showa Highpolymer Co., Ltd.) composed of 1,4-butanediol and a 4:1 mixture of succinic acid and adipic acid was mixed with 60 wt.% of poly-ε-caprolactone (product of Union Carbide Corp.) at 100°C. The sample so obtained was heat sealed at 130 °C for 5 minutes, whereby a sheet having a thickness of 0.2 mm was produced. The sheet was formed into a bag of 20 mm in width and 25 mm in length, which was filled with 100 mg of Z-11-hexadecenal, which was a sex hormone of diamond black moth ( Plutella xylostella ). The release rate of Z-11-hexadecenal from the sustained-release preparation so obtained was measured under the conditions at 30°C and 1 m/s. As a result, it continued uniform release at 2.1 mg/day for about 40 days and therefore had excellent stable releasability over a long period of time. When the above sustained-release preparation was buried in the ground from April to October, it was worn out and degradation proceeded even to cause disappearance of a portion of it. The equilibrium swelling ratio at 40°C of poly-E-caprolactone (product of Union Carbide Corp.), which was used as a modifier, to Z-11-hexadecenal was 8.3 wt.%. Comparative Example 1 In a similar manner to Example 1 except that only a polycondensate (product of Showa Highpolymer Co., Ltd.) composed of 1,4-butanediol and a 4:1 mixture of succinic acid and adipic acid was used, a sustained-release preparation was prepared. As a result of the evaluation of the release rate of the preparation so obtained, it continued uniform release at 0.9 mg/day for about 100 days. In order to secure the similar release rate to Example 1, however, at least twice the amount of the sustained-release preparation was necessary. In addition, owing to a small release rate, a large amount of the active ingredient remained even after the expiration of the necessary period so that the preparation in Comparative Example 1 was not suited for practical use. Example 2 In a twin roll, a polycondensate (product of Showa Highpolymer Co., Ltd.) composed of 1,4-butanediol and succinic acid was mixed with 30 wt.% of poly-ε-caprolactone (product of Union Carbide Corp.) at 120°C. The sample so obtained was heat sealed at 150 °C for 5 minutes, whereby a sheet having a thickness of 0.2 mm was produced. The sheet was formed into a bag of 25 mm in width and 30 mm in length, which was filled with 100 mg of E,E-8,10-dodecadienol, which was a sex hormone of codlin moth ( Cydia pomonella ). The release rate of E,E-8,10-dodecadienol from the sustained-release preparation so obtained was measured under the conditions at 30°C and 1 m/s. As a result, it continued uniform release at 1.7 mg/day for about 50 days and therefore had excellent stable releasability over a long period of time. When the sustained-release preparation was buried in the ground from April to October, it partially disappeared and degradation proceeded even to lose original shape. The equilibrium swelling ratio at 40°C of poly-ε-caprolactone (product of Union Carbide Corp.), which was used as a modifier, to E,E-8,10-dodecadienol was 8.9 wt.%. Comparative 2 In a similar manner to Example 2 except that only a polycondensate (product of Showa Highpolymer Co., Ltd.) composed of 1,4-butanediol and succinic acid was used, a sustained-release preparation was prepared. As a result of the evaluation of the release rate of the preparation so obtained, it continued uniform release at 0.6 mg/day for about 150 days. In order to secure the similar release rate to Example 2, however, at least three times the amount of the sustained-release preparation was necessary. In addition, owing to a small release rate, a large amount of the active ingredient remained even after the expiration of the necessary period so that the preparation in Comparative Example 2 was not suited for practical use. Example 3 In a twin roll, polylactic acid (product of Cargill Corp.) was mixed with 40 wt.% of poly-E-caprolactone (product of Union Carbide Corp.) at 150°C. The sample so obtained was heat sealed at 160 °C for 5 minutes, whereby a sheet having a thickness of 0.3 mm was produced. The sheet was formed into a bag of 20 mm in width and 25 mm in length, which was filled with 90 mg of Z-11-tetradecenyl acetate, which was a sex hormone of a leaf folder. The release rate of Z-11-tetradecenyl acetate from the sustained-release preparation so obtained was measured under the conditions at 30°C and 1 m/s. As a result, it continued uniform release at 1.9 mg/day for about 40 days and therefore had excellent stable releasability over a long period of time. When the sustained-release preparation was buried in the ground from April to October, the end portion of it disappeared and the preparation itself became considerably fragile and was degraded to an easily cracked extent. The equilibrium swelling ratio at 40°C of poly-ε-caprolactone (product of Union Carbide Corp.), which was used as a modifier, to Z-11-tetradecenyl acetate was 7.1 wt.%. Comparative Example 3 In a similar manner to Example 3 except that only polylactic acid (product of Cargill Corp.) was used, a sustained-release preparation was produced. As a result of the evaluation of the release rate, the preparation showed a release rate of only 0.01 mg/day and was therefore not suited for practical use. Comparative Example 4 In a similar manner to Example 3 except that only 0.5 wt.% of poly-ε-caprolactone (product of Union Carbide Corp.) was mixed, a sustained-release preparation was produced. As a result of the evaluation of the release rate, the preparation showed a release rate of only 0.01 mg/day and no modifying effect was observed. Comparative Example 5 To polylactic acid (product of Cargill Corp.), 30 wt.% of a polycondensate (product of Showa Highpolymer Co., Ltd.) composed of 1,4-butanediol and a 4:1 mixture of succinic acid and adipic acid were added and in a twin roll, they were mixed at 150°C, whereby a sample was prepared. Using the sample, a sustained-release preparation was produced in a similar manner to Example 3. As a result of the evaluation of the release rate, the preparation showed a release rate of only 0.04 mg/day and no modifying effect was observed. Incidentally, the equilibrium swelling ratio at 40°C of the polycondensate (Showa Highpolymer) composed of 1,4-diol and a 4:1 mixture of succinic acid and adipic acid to Z-11-tetradecenyl acetate was 0.8 wt.%. Example 4 To a polycondensate (product of Showa Highpolymer Co., Ltd.) composed of 1,4-butanediol and a 4:1 mixture of succinic acid and adipic acid, which had been used in Example 1, 40 wt.% of an ethylene-vinyl acetate copolymer (product of Mitsubishi Chemical; a vinyl acetate content: 15 wt.%) were added. In a twin roll, they were mixed at 100°C. The sample so obtained was heat sealed at 130 °C, whereby a sheet having a thickness of 0.2 mm was produced. The sheet was formed into a bag of 20 mm in width and 20 mm in length, which was filled with 90 mg of Z-11-tetradecenyl acetate in a similar manner to Example 3. The release rate of Z-11-tetradecenyl acetate from the sustained-release preparation so obtained was measured under the conditions at 30°C and 1 m/s. As a result, it continued uniform release at 2.0 mg/day for about 40 days and therefore had excellent stable releasability over a long period of time. When the sustained-release preparation was buried in the ground from April to October, it partially disappeared and was considerably worn out. The equilibrium swelling ratio at 40°C of the ethylene-vinyl acetate copolymer (product of Mitsubishi Chemical Co., Ltd.; a vinyl acetate content: 15 wt.%), which was used as a modifier, to Z-11-tetradecenyl acetate was 29.1 wt.%. Comparative Example 6 In a similar manner to Example 4 except that 91 wt.% of an ethylene-vinyl acetate copolymer (product of Mitsubishi Chemical Co., Ltd.; a vinyl acetate content: 15 wt.%) was added, a sustained-release preparation was produced. As a result of the evaluation of the release rate, the preparation showed uniform release at 3.1 mg/day for about 20 days but it was accompanied with the inconvenience that the pheromone oozed out on the surface of the preparation and became sticky. When the sustained-release preparation so obtained was buried in the ground from April to October, no apparent change was observed and biodegradation did not occur. Comparative Example 7 In a similar manner to Example 4, the release rate of "Hamakicon" (trade name; product of Shin'etsu Chemical Co., Ltd.) which was a mating disruption agent of a leaf folder was evaluated. As a result, it showed uniform release at 1.9 mg/day for about 35 days and after that, the release rate showed a gradual decrease. In addition, the preparation was buried in the ground from April to October but no change was observed. Example 5 To a polycondensate (product of Showa Highpolymer Co., Ltd.) composed of 1,4-butanediol and a 4:1 mixture of succinic acid and adipic acid, which was similar to that used in Example 1, 30 wt.% of an ethylene-ethylene acrylate copolymer (product of Nippon Unicar Co., Ltd.; an ethyl acrylate content of 10%) were added. They were mixed at 100°C in a twin roll. The sample so obtained was pelletized by a sheet pelletizer, followed by the formation of a capillary tube having an internal diameter of 0.8 mm and a wall thickness of 0.5 mm by an extruder. The capillary tube so formed was filled with Z,Z/E-7,11-hexadecadienyl acetate, which was a sex pheromone of Pectinophora gossypiella and then heat sealed at every 20 cm length, whereby a sustained-release preparation was produced. The release rate from the sustained-release preparation so obtained was measured under the conditions at 30°C and 1 m/s. As a result, the preparation continued release at 0.8 mg/day for about 70 days and was therefore excellent in the stable release over a long period of time. When the preparation so obtained was buried in the ground from April to October, it retained its shape but was covered with mold on the surface and was easily worn out. Thus, an advance of biodegradation was observed. The equilibrium swelling ratio at 40°C of the ethylene-ethyl acrylate copolymer (product of Nippon Unicar Co., Ltd.; an ethyl acrylate content of 10%), which was used as a modifier, to Z,Z/E-7,11-hexadecadienyl acetate was 18.4 wt.%. Comparative Example 8 In a similar manner to Example 5, "PB-Rope" (trade name; product of Shin-Etsu Chemical Co., Ltd.), which was a mating disruption agent for Pectinophora gossypiella was evaluated. As a result, the preparation continued uniform release at 0.8 mg/day for about 70 days, which was equivalent to the case of Example 5. When the above sustained-release preparation was buried in the ground from April to October, no apparent change was observed. It was not torn to pieces even if drawn by hands and no degradation occurred. Example 6 To a polycondensate (product of ZENECA K.K.) of 3-hydroxyacetic acid and hydroxyvaleric acid, 30 wt.% of poly-E-caprolactone (product of Union Carbide Corp.) were added. They were mixed at 140°C in a twin roll. The sample so obtained was pelletized by a sheet pelletizer, followed by the formation of a capillary tube having an internal diameter of 0.8 mm and wall thickness of 0.5 mm by an extruder. The capillary tube so formed was filled with Z-8-dodecenyl acetate, which was a sex pheromone of Grapholita molesta and was heat sealed and cut at every 20 cm, whereby a sustained-release preparation was produced. The release rate from the sustained-release preparation was measured under the conditions at 30°C and 1 m/s. As a result, the preparation continued uniform release at 1.6 mg/day for about 40 days and was excellent in the stable release over a long period of time. When the above sustained-release preparation was buried in the ground from April to October, it barely retained its shape and was considerably fragile. It was degraded to an extent easily torn into pieces by hands. The equilibrium swelling ratio at 40°C of poly-ε-caprolactone (product of Union Carbide Corp.), which was used as a modifier, to Z-8-dodecenyl acetate was 9.9 wt.%. Example 7 To poly-ε-caprolactone (product of Union Carbide Corp.), 10 wt.% of polyvinyl acetate (product of Aldrich Chemical Co., Inc.) were added. They were mixed at 90°C in a twin roll. The sample so obtained was pelletized by a sheet pelletizer, followed by the formation of a bottle having a thickness of 2 mm, an internal volume of 5 ml and outer surface area of 25 cm 2 by a blow molder. The bottle was filled with 1 g of Geraniol having a rose odor, followed by heat sealing of an inlet opening, whereby a sustained-release preparation was produced. When the sustained-release preparation so obtained was placed inside of a room, it emitted a rose odor over about 2 months. The result was therefore satisfactory. When the above sustained-release preparation was buried in the ground from April to October, it retained its shape but was covered with mold and decreased in weight by 9%. Thus, progress of the biodegradation by microorganisms was observed. The equilibrium swelling ratio at 40°C of polyvinyl acetate (product of Aldrich Chemical Co., Inc.), which was used as a modifier, to geraniol was 12.9 wt.%. As can be understood from the above description, the use of the sustained-release preparation according to the first group of the present invention makes it possible to release the active ingredient stably over a long period of time, thereby maintaining its effects for a long time. It is also possible to secure a large release rate of the active ingredient, which makes it possible to reduce the size of the preparation and reduce the number of the preparations to be placed, leading to the cost reduction. Moreover, owing to the biodegradability, the preparation is free from collection after application and is therefore labor saving in agricultural applications. It is also useful from the viewpoint of the environmental protection, because it is degraded by microorganisms and does not remain in the soil. 2. Biodegradable pheromone dispenser (according to the second group of the invention) In the second group of the present invention, employed as a sustained-release layer of a pheromone is an aliphatic polyester wherein in the recurring units forming a polymer, a ratio (I/II) of (I) the number of the carbon atoms constituting the main chain and not relating to the ester linkage to (II) the number of the carbon atoms constituting the ester linkage is larger than 2. The term "(I) the number of the carbon atoms constituting the main chain and not relating to the ester linkage" as used herein means the number of carbon atoms other than those forming an ester linkage in the main chain structure and does not contain the number of carbon atoms of the side chain. The term "a ratio (I/II) of (I) the number of the carbon atoms constituting the main chain to (II) the number of the carbon atoms constituting the ester linkage" as used herein means a value of one of the recurring units forming the polymer and in the case of a polyester having at least three monomers, it means weighted mean of the respective recurring units according to these monomer compositions. In other words, it means the total of the values obtained by multiplying a ratio (I/II) of each monomer by the proportion of each monomer composition supposing that the whole composition is 1. For example, in the case of an aliphatic polyester having the following recurring units, the number (I) of the carbon atoms of the main chain is the sum total of (a) parts and the number (II) of the carbon atoms forming an ester linkage is the sum total of (b) parts. The number (I) of carbon atoms forming the main chain: (I) = (4 + 2) x 0.8 + (4 + 4) x 0.2 = 6.4 The number (II) of carbon atoms constituting an ester linkage (II) = 2 x 0.8 + 2 x 0.2 = 2 Accordingly, the ratio (I/II) = 6.4/2 = 3.2 Examples of such an aliphatic polyester include condensation and polymerization products between a C 2-20 carboxylic acid such as malonic acid, succinic acid, succinic anhydride, glutaric acid, adipic acid, adipic anhydride, sebacic acid, fumaric acid, maleic acid, didodecanoic acid, malic acid, tartaric acid or citric acid and a C 2-20 alcohol such as ethylene glycol, propylene glycol, butanediol, hexanediol, octanediol, decanediol, cyclohexane dimethanol, glycerin, or trimethylol propane; and ring-opening polymers of a cyclic ester such as ε-caprolactone. As such a aliphatic polyester, those having a side chain may be used, but it is necessary that the ratio (I/II) of the number (I) of the carbon atoms constituting the main chain and not relating to an ester linkage to the number (II) of the carbon atoms forming the ester linkage is at least 2. When the ratio (I/II) is smaller than 2, the static bond of the polymer segment becomes firmer, which lowers the transmission of a pheromone, thereby making impossible to maintain a release rate necessary for the pest control. No particular limitation is imposed on the ratio of (I/II) insofar as it is not smaller than 2, but the ratio of 20 or smaller is preferred for preventing excessive release of a pheromone. The aliphatic polyester may be a single composition such as ring-opening polymerization product or may be a polycondensate composed of a dicarboxylic acid and a diol derivative. An aliphatic polyester composed of at least three monomer units is however preferably used to properly control the release performance of a pheromone. It may be a random copolymer or may have a structure of a block copolymer available by coupling or the like. An aliphatic polyester obtained by polymer blend of at least three monomer units may also be used. No particular limitation is imposed on the shape of a dispenser, but a reservoir type having therein a pheromone as a liquid phase is preferred. It is desired that this dispenser encapsulates a pheromone therein and is not equipped with an opening such that the pheromone is brought in direct contact with the outside air. As a container satisfying the above condition, tube-, bottle- and bag-shaped containers are suited. Obviously, these containers may additionally have a jig such as stick or attachment for attaching the pheromone to a material to be treated such as crops. In such a reservoir type dispenser, the wall surface of the reservoir itself constitutes a sustained release layer of a pheromone. The pheromone held by a liquid phase transmits through a sustained release layer forming a preparation and is released. For the stable sustained release, thickness of at least 0.02 mm is necessary. The thickness smaller than 0.02 mm is not suited because it causes pinholes or excessive release of the active ingredient such as pheromone. There occurs no particular problem when the sustained release layer has a thickness not smaller than 0.02 mm, but that ranging from 0.05 mm to 5 mm is more preferred. When it exceeds 5 mm, the release amount of a pheromone tends to become too small, which requires much widening of a release area. So, such a thickness is not suited for practical use. The release surface area of the sustained release preparation is required to be 1 cm 2 or larger. Surface areas smaller than 1 cm 2 make it difficult to secure a sufficient release amount for pest control and are therefore not suited. No particular problem occurs when the release surface area is 1 cm 2 or larger, but a range of from 2 cm 2 to 2 m 2 is more preferred. Surface areas exceeding 2 m 2 are not practical because it is difficult to attach the preparation having such a large surface area. The pheromone to be enclosed in a dispenser may be encapsulated in portions. The encapsulated amount is preferably at least 1 mg, more preferably at least 5 mg. It is difficult to encapsulate an amount less than 1 mg in the dispenser. As the dispenser, a tube-, bottle- and bag-shaped containers are preferred. In the case of the tube-shaped container, that having an internal diameter of 0.4 mm to 10 mm is preferred. Internal diameters smaller than 0.4 mm make it difficult to fill the pheromone in the container, while those larger than 10 mm make it difficult to conduct encapsulation. The bottle-shaped preparation is formed by blow molding or injection molding and preferred is that having an internal volume of 0.1 to 200 ml. The bottle having an internal volume less than 0.1 ml cannot be formed easily, while that having an internal volume greater than 200 ml is not economical because there is a large difference between the amount of the pheromone filled therein and the internal volume. In the case of a bag-shaped preparation, the amount of the pheromone filled in the bag is desirably 1 mg to 100 g. Neither amounts smaller than 1 mg nor exceeding 100 g are preferred because it is difficult to fill such an amount in the bag. The pheromone dispenser is required to have means to attach the dispenser to a material to be treated such as crops and means known to date can be employed for it. As a tube-shaped dispenser, dispensers having a metal wire installed thereto and having shapability are given as examples. Described specifically, exemplified is a tube-shaped container produced by disposing a metal wire along a longitudinal direction of the main body of the container, covering the metal wire with a resin material forming the container and then integrating the body and the wire by molding. Any material can be employed as the metal wire because it has no influence on the performance of the pheromone dispenser. It is desired to use a material which tends to cause oxidation and deterioration such as iron wire so as not to impair the characteristics of the biodegradability. Furthermore, the pheromone dispenser according to the present invention is desired to have, in advance, a shape permitting the attachment to a material to be treated. FIG. 1 illustrates a shape feasible as a tube-shaped dispenser. In this dispenser, a tube-shaped reservoir containing a pheromone therein is folded or bent into a proper shape. A spiral-shaped, a ring-shaped, square-shaped and triangle-shaped dispensers are indicated at numerals 11, 12, 13 and 14, respectively. It is also possible to form into other polygonal shapes or even to form into a star shape. Indicated at numerals 15 and 16 are swirl shape and 9 shape. In addition, a pine needle shape in which plural tubes are linked at their one end as indicated at numeral 17 and a cyclic tube in which plural tubes are linked and integrated at their both ends as shown at numeral 18 can be exemplified. In addition, as illustrated in FIG. 2, bottle-shaped or bag-shaped dispensers can be formed as those having a hook or cyclic filament connected therewith. In FIG. 2, illustrated at numeral 21 is a dispenser equipped with a hook portion 22. This dispenser 21 has a bag-shaped portion 23 for storing a pheromone therein. In this dispenser, the bag-shaped portion 23 is formed by laminating two aliphatic polyester films constituting a sustained release layer and the hook portion 22 can be formed integrally with the bag-shaped portion by using the same material. Illustrated at 31 is a dispenser equipped with a hook portion 32 of another shape and it has a bag-shaped portion 33. It is similar to the above dispenser 21 in the basic structure. Illustrated at 41 is a dispenser equipped with a hook portion 42 of a further shape and has a bag-shaped portion 43. It is similar to the above dispenser 21 in the basic structure. Illustrated at 51 is a dispenser equipped with a filament portion 52 of a still further shape and has a bag-shaped portion 53. It is similar to the above dispenser 21 in the basic structure. Incidentally, the above bag-shaped portions 23, 33, 43 and 53 can be replaced by bottle-shaped portions. Another bag-shaped dispenser, as illustrated in FIG. 3, is a dispenser 61 in which aliphatic polyester films are laminated each other to form a bag and a hole 63 is made in the laminated film 62. Upon application, an end 64 far from the hole is inserted into the hole 63, whereby the dispenser can be wound round a material to be treated such as branch. This dispenser 61 has a storing bag 65 for enclosing a pheromone therein. No particular limitation is imposed on the pheromone usable in the present invention. Any pheromone such as alarm pheromone, trail marking pheromone or class differentiation pheromone can be used but a sex pheromone is suited to carry out pest control efficiently. Known examples of the sex hormone include unsaturated aliphatic hydrocarbons having 10 to 20 carbon atoms, acetates, aldehydes, alcohols, ketones and epoxy compounds. In general, they may be used either singly or in combination. More specifically, those exemplified as the active ingredient in the first group of the present invention can be employed. The sustained-release layer of the biodegradable pheromone dispenser according to the second group of the present invention should retain its essential performance during application so that a pigment or dye, or various stabilizers such as ultraviolet absorber or antioxidant may be added to it in order to improve the weather resistance. Example 8 A sheet of 0.1 mm thick was formed by hot pressing a polycondensate (product of Showa Highpolymer Co., Ltd.) composed of 1,4-butanediol and a 4:1 mixture of succinic acid and adipic acid at 130 °C for 5 minutes. The sheet was formed into a bag of 20 mm in width and 30 mm in length, which was filled with 90 mg of Z-11-tetradecenyl acetate, which was a sex hormone of a leaf folder. The release rate of Z-11-teteradecenyl acetate from the dispenser so formed was measured under the conditions at 30°C and 1 m/s. As a result, the dispenser continued uniform release at 2.0 mg/day for about 40 days and therefore had excellent releasability. The release surface area of the dispenser was 12 cm 2 . In the aliphatic polyester, the ratio (I/II) of the carbon atoms (I) constituting the main chain and not relating to ester linkage to the carbon atoms (II) constituting the ester linkage was 3.2 When the above dispenser was buried in the ground from April to October, it was worn out and almost lost its original form. Comparative Example 9 A sheet of 0.1 mm thick was formed by hot pressing polylactic acid (product of Cargill Corp.) at 160°C for 5 minutes. In a similar manner to Example 8, the release rate of Z-11-tetradecenyl acetate was measured. As a result, it showed a release rate of only 0.1 mg/day or so and was not suited for practical use. The ratio (I/II) of the aliphatic polyester was 1.0. Comparative Example 10 A sheet of 0.1 mm thick was formed by hot pressing a polycondensate (product of ZENECA K.K.) between 3-hydroxybutyric acid and 3-hydroxyvaleric acid at 160°C for 5 minutes. In a similar manner to Example 8, the release rate of Z-11-tetradecenyl acetate was measured. As a result, it showed only a release rate of about 0.5 mg/day and was found not suited for practical use. The ratio (I/II) of the aliphatic polyester was 2.0. Comparative Example 11 In a similar manner to Example 8, the release rate of "Hamakikon" (trade name; product of Shin'etsu Chemical Co., Ltd.) which was a mating disruption agent of a leaf folder was measured at 30°C and 1 m/s. As a result, it showed uniform release at 1.9 mg/day for about 35 days but after that, the release rate showed a gradual decrease. The above dispenser was buried in the ground from April to October but no change was observed. Example 9 A tube having an internal diameter of 0.8 mm and a wall thickness of 0.5 mm was formed by extruding the aliphatic polyester as employed in Example 8. The tube so formed was filled with Z-8-dodecenyl acetate, which was a sex pheromone of Grapholita molesta , and heat sealed and cut at every 20 cm, whereby a pheromone dispenser having Z-8-dodecenyl acetate encapsulated therein was obtained. The release rate from the dispenser was measured under the conditions at 30°C and 1 m/s. As a result, the dispenser continued uniform release at 1.9 mg/day for about 35 days and was found to be suited for practical use. Incidentally, the release surface area of the above dispenser was 11 cm 2 . Example 10 A film of 0.06 mm thick was formed by T-die extrusion of, as an aliphatic polyester, a polycondensate (product of Showa Highpolymer Co., Ltd.) composed of 1,4-butanediol and a 4:1 mixture of succinic acid and adipic acid. The sheet was formed into a bag of 25 mm in width and 30 mm in length, followed by filling with 100 mg of E,E-8,10-dodecadienol, which was a sex hormone of codlin moth ( Cydia pomonella ), whereby a dispenser was obtained. The release rate from the dispenser so obtained was measured under the conditions at 30°C at 1 m/s. As a result, it continued uniform release at 1.4 mg/day for about 65 days and therefore was found to be suited for practical use. Incidentally, the release surface area of the dispenser was 15 cm 2 . The ratio (I/II) of the aliphatic polyester was 3.0. When the dispenser was buried in the ground from April to October, it was worn out and a portion of it had already disappeared. Comparative Example 12 In a similar manner to Example 10 except that a film of 0.01 mm thick was used instead, a pheromone dispenser was obtained. The release rate from the dispenser was measured under the conditions at 30°C and 1 m/s. As a result, it showed excessive release of 5.4 mg/day and the pheromone oozed out on the surface of the dispenser and became sticky. The dispenser was therefore found not suited as a pheromone dispenser. Example 11 A bottle having a thickness of 1 mm, an internal volume of 0.5 ml and an outer surface area of about 8 cm 2 was formed by blow molding of poly-ε-caprolactone (product of Union Carbide Corp.). The bottle so formed was filled with 100 mg of a 1:1 mixture of Z-11-hexadecenyl acetate and Z-11-hexadecenal which mixture was a sex pheromone of diamond black moth ( Plutella xylostella ), whereby a pheromone dispenser was obtained. The release rate from this dispenser under the conditions at 30°C and 1m/s was measured. As a result, the dispenser continued uniform release for about 55 days at 1.5 mg/day and was found to be suited for practical use. The ratio (I/II) of the aliphatic polyester was 5.0. The above dispenser was buried in the ground from April to October. No apparent external change was found but its weight showed a 8% decrease owing to biodegradation by microorganims. Example 12 In a twin roll, a polycondensate (product of ZENECA K.K.) between 3-hydroxybutyric acid and 3-hydroxyvaleric acid and poly-ε-caprolactone (product of Union Carbide Corp.) were charged at a ratio of 7:3 and kneaded. The aliphatic polyester so obtained was hot pressed at 160°C for 5 minutes, whereby a sheet of 0.1 mm thick was obtained. In a similar manner to Example 8, the release rate of Z-11-tetradecenyl acetate from the sheet was measured. As a result, the sheet continued uniform release for about 40 days at a rate of 2.1 mg/day and was found to have excellent releasability. The above sheet-shaped dispenser had a release surface area of 12 cm 2 , and the ratio (I/II) of the aliphatic polyester was 2.9. When the above dispenser was buried in the ground from April to October, it was worn out and almost disappeared. Example 13 Two tube-shaped dispensers formed in Example 9 were placed side by side. Ends at the same side of these two dispensers were heat sealed, whereby a cyclic-shaped dispenser was formed. To a peach tree, 10 cyclic dispensers so formed were attached. Five of them were attached so that the branch of the tree is passed through a cyclic portion formed by opening the space between two tube-shaped dispensers and the remaining five dispensers were attached by winding each of the dispensers around the branch and then passing one end of the dispenser through the cyclic portion formed by the other end of the dispenser and the branch. They were installed from April to August. No dispensers fell down and were found to be suited for practical use. As is apparent from the above description, the biodegradable pheromone dispenser according to the second group of the present invention makes it possible to release the hormone stably, thereby conducting pest control over a long period of time. In addition, owing to biodegradability, it does not need collection after application and is therefore labor saving. Furthermore, it is degraded completely by microorganisms and does not remain in the soil so that it is excellent from the viewpoint of environmental protection.

Claims: A biodegradable sustained-release preparation comprising an active ingredient held and released by a sustained release layer, the sustained release layer comprising a mixture of 99 to 10 parts by weight of an aliphatic polyester and 1 to 90 parts by weight of a polymeric modifier for the regulation of sustained releasability of the active ingredient transmitted through the sustained release layer, wherein the active ingredient is encapsulated in a container formed from the sustained release layer in the form of a tube, bottle or bag, and the sustained release layer degrades after application. A preparation according to claim 1, wherein the active ingredient is released by means of transmission. A preparation according to clam 1 or 2, wherein the modifier has an equilibrium swelling ratio at 40°C of at least 2 wt.%. A preparation according to claim 1 or 3, wherein the active ingredient is a pheromone. A preparation according to any one of claims 1 to 4, wherein the modifier is at least one compound or a mixture of compounds selected from the group consisting of poly-ε-caprolactone, polyvinyl acetate, ethylene-vinyl acetate copolymer, ethylene-ethyl acrylate copolymer, polyvinyl chloride, polymethacrylic esters and cellulose derivatives. A biodegradable sustained-release preparation, as claimed in any preceding claim, wherein the active ingredient is in a liquid phase. A biodegradable pheromone dispenser in which an aliphatic polyester is used as a sustained release by transmission layer for a pheromone contained therein in a liquid phase, said aliphatic polyester has recurring units whose ratio (I/II) is more than 2, where (I) is the number of the carbon atoms constituting the main chain but not those relating to an ester linkage and (II) is the number of the carbon atoms constituting the ester linkage, wherein the pheromone is encapsulated in a dispenser formed from the transmission layer, and the transmission layer degrades after application. A dispenser according to claim 7, wherein the dispenser has a pheromone encapsulated therein, is shaped not to have an opening, and has a sustained release layer of a least 0.02 mm in thickness and a release surface area of at least 1 cm 2 A dispenser according claim 7 or claim 8, wherein the aliphatic polyester is composed of at least three monomer units. A dispenser according to any one of claims 7 to 9, which is shaped for attachment to a material to be treated.

Inventors: SAKURADA TOYOHISA, SUZUKI HIROSHI, SAKURADA, TOYOHISA, SUZUKI, HIROSHI, Sakurada, Toyohisa, Shin-Etsu Chemical Co., Ltd., SUZUKI, HIROSHI, SHIN-ETSU CHEMICAL CO., LTD.
Applicants: RES ASS FOR BIOTECHNOLOGYOF AG, RESEARCH ASSOCIATION FOR BIOTECHNOLOGYOF AGRICULTURAL CHEMICALS
Application year: 1997
Main classification: C08L67
IPC codes: A01N25, A01M1, B65D65, A01N37, A01M5, A01M29