Pheromone immobilized in stable hydrogel microbeads

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Biocides; animal or insect repellents or attractants

Reexamination Certificate

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C424S084000, C424S450000, C424S488000, C424S407000, C424S404000, C424S405000, C424S489000, C424S486000, C424S487000

Reexamination Certificate

active

06562361

ABSTRACT:

FIELD OF THE INVENTION
The invention relates broadly to a combination of encapsulation, immobilization and release of active material using hydrogel microbeads. Specifically, the active material is encapsulated in a coacervate shell and immobilized in a hydrophilic microbead.
BACKGROUND
Methods of eliminating unwanted pests from orchards, crops and forests frequently entail the use of organophosphate insecticides. Alternative methods involve insect mating disruption, where insect pheromones are used to control pests and protect agricultural crop. In insect mating disruption methods, the mating pheromone plume of a female insect is typically masked with other pheromone point sources. This reduces the likelihood of a male insect finding a female, and subsequently disrupts and reduces larvae production. The insect population of the next generation is thus decreased, as well as potential crop damage.
Conventional sprayable pheromone formulations are generally provided in liquid filled microcapsules containing an active. Typically, the microcapsules have a polyurea shell that can be formed using an interfacial process involving an isocyanate and an amine. Microencapsulation by this method has been descibed for example in U.S. Pat. No. 4,487,759 (Nesbitt et al.) These polyurea shells allow actives to be released into the atmosphere for up to a total of 2-3 weeks for most insect pheromones. Shells of polyurea capsules are generally semi-permeable, therefore active material can diffuse across the shells and release slowly with time. Potentially, high concentrations of active in the air can be observed immediately upon delivery or spraying of encapsulated products. This may be attributable to a high occurrence of capsule bursts or potential leaks in microcapsules.
U.S. Pat. No. 4,532,123 (Gardner) teaches capsules containing a pharmaceutical active material in primary capsules, that are further encapsulated within a second shell to create secondary capsules. The intracapsular liquid core of the secondary capsules contain enzymes which slowly hydrolyze the shell of the primary capsules. This slow hydrolysis enables the slow release of active from the primary capsules into the larger capsular core for controlled delivery.
A Japanese patent, JP 8-173794 teaches encapsulation of an amine within small capsules of polymethyl methacrylate shells. These capsules are further encapsulated within an epoxy-amine polymeric shell. Similarly, the amine within the tiny capsules is released into the core of the larger capsule ultimately delivering the amine upon rupturing of the polymeric shells.
Use of interfacial condensation to encapsulate substances such as pharmaceuticals, pesticides and herbicides is taught in U.S. Pat. No. 3,577,515 (Vandegaer). The encapsulation process involves two immiscible liquid phases (typically water and an organic solvent), one being dispersed in the other by agitation, and the subsequent polymerization of monomers from each phase at the interface between the bulk (continuous) phase, and the dispersed droplets. Polyurethanes and polyureas are materials suitable for producing the microcapsules. The microcapsules comprising a polymeric sphere and a liquid centre, ranging from 30 micron to 2 mm in diameter, depending on monomers and solvents used.
Highly viscous and thickened hydrogels have been used to deliver pheromones, fragrances and other non-water soluble actives. U.S. Pat. No. 4,755,377 (Steer) describes a process of encapsulating perfume or fragrant material within an aqueous-based gel composition. The resulting material is in the form of a highly viscous semi-solid. U.S. Pat. No. 5,645,844 (Henderson et al.) describes the use of chitosan paste for delivery of pheromones to disrupt insect mating, where the material can be dispensed by an apparatus such as a caulking gun. Due to their thickness and high viscosity, these materials, however, are generally unsprayable compositions.
Most hydrogels are safe and non-toxic to humans. Hydrogels have been used for the encapsulation of biological materials whereby the formulation is non-lethal to the viability of the cells, proteins, and related materials. U.S. Pat. No. 4,689,293 (Goosen et al.) describes the process of encapsulating living tissue or cells. The encapsulation shell permits the passage of materials and oxygen to the cells and permits the diffusion of the metabolic by-products from the gel.
Coacervation process is well known in the art for uses such as carbonless copy paper capsules and in encapsulation of leuco dyes, drugs, flavorings and fragrances. U.S. Pat. No. 2,800,457 (Green) discloses a gelled colloid that is porous and that the pores may be tightened if the crosslinking step is conducted at pH of 9-10.
Other approaches to crosslinking a coacervate microcapsule have employed non-aldehyde crosslinkers. U.S. Pat. No. 4,402,856 (Schnoring) discloses the use of a natural and/or synthetic tanning agent and a carbonyl compound to harden a gelatin microcapsule. U.S. Pat. No. 5,023,024 (Kyogoku et al.) discloses the use of naturally occurring chemicals of the iridoid class, specifically genipin. U.S. Pat. No. 5,051,304 (David et al.) also discloses the use of tannic acid as a crosslinker.
Although the foregoing approaches have proved satisfactory for crosslinking a coacervate shell under certain conditions, the need still exists to provide coacervate shells that are more environmentally friendly, do not utilize toxic crosslinkers, and are more cost effective than previously disclosed.
SUMMARY OF THE INVENTION
The present invention provides a method of encapsulating a pheromone comprising:
a) providing a solution comprising a first polymer capable of forming a microcapsule by complex coacervation; a pheromone; and a second polymer, said second polymer being capable of forming a microcapsule by complex coacervation with the composition comprising the first polymer;
b) establishing a microcapsule having a coacervation shell without chemical crosslinking of said shell;
c) adding a third polymer, said third polymer being suitable to form a hydrogel microbead, in an amount effective to form the microcapsule containing composition; and
d) spraying the microcapsule containing composition into a coordination solution, thereby providing stable hydrogel microbeads comprising microcapsules having a coacervation shell without chemical crosslinking.
Another aspect of the present invention is a method of encapsulating a pheromone wherein the third polymer of step c) above is added before the microcapsule of step b) is established.
The present invention also provides a pheromone that is encapsulated in a coacervate shell by the above named process.
The hydrogel microbead is preferably hydrophilic and is capable of immobilizing a broad spectrum of microencapsulated active materials, either water-soluble or non-water soluble.
In an aspect of the invention, the hydrogel microbead may be made from a water-soluble microcapsule containing material to provide an environmentally friendly microbead. The microbeads may be coated with an adhesive to improve application in an intended environment.
In a further aspect of the invention, the microbeads may be capable of re-hydrating after an initial dehydration and release of active. Thus, the release and longevity of the pheromone can be controlled by adjusting the humidity of the environment in which the microbeads have been delivered.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention provides a pheromone encapsulated within a coacervate shell which in turn is entrained within a hydrogel microbead without an intermediate step of chemically crosslinking the coacervate shell. For purposes of the present invention, a chemical crosslink is a crosslink between two polymers formed by covalent bonds. Thus, the present invention provides effective delivery of pheromones from a hydrogel microbead structure without the use of potentially environmentally unfriendly chemicals, thus avoiding the use of chemicals such as glutaraldehyde, formaldehyde, and tannic acid, among others.

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