Microcapsules and method of preparing same

Claim 2

In ethylcellulose microcapsules comprising (i) particles of a core material and (ii) ethylcellulose coating walls deposited on and around said particles of the core material, the improvement wherein a polymer material which shows at least 1.2 times increase in weight by immersing it in water at 37°C is incorporated into the ethylcellulose coating walls and/or the core material of the microcapsules.

Claim 3

The ethylcellulose microcapsules of Claim 1, in which said polymer material is selected from the class consisting of starch, crystalline cellulose, agar, alginic acid or its alkali earth metal salt, hydroxy-lower alkyl-polysaccharide, carboxy-lower alykyl-poylysaccharide or its alkali earth metal salt, a graft copolymer of polysaccharide, polyvinylalcohol or gelatin with a monomer of the formula: CH 2 = C(R ) - Y (wherein R 1 is hydrogen or methyl, and Y is carboxy, nitrile, lower alkoxycarbonyl or 2-pyrrolidon-l-yl), a cross-linked polysaccharide, a cross-linked polyyinyl_ alcohol, a cross-linked gelatin, a cross-linked polyacrylic acid or its alkali metal salt, and a copolymer of divinylbenzen with a monomer of the formula: CH 2 = C( R 2 ) - X (wherein R 2 is hydrogen or methyl, and X is carboxy, lower alkoxycarbonyl, lower alkanoyloxy, or 2-pyrrolidon-1-yl).

Claim 4

The ethylcellulose microcapsules of Claim 1, in which said polymer material is selected from the class consisting of starch, crystalline cellulose, alginic.acid or its alkali earth metal salt, agar, hydroxy-lower alkyl-cellulo hydroxy-lower alkyl-starch, carboxy-lower alkyl-cellulose, carboxy-lower alkyl-starch or its alkali earth metal salt, a graft copolymer of starch, cellulose or polyvinylalcohol with a monomer of the formula: CH 2 = C(R 1 ) - Y' (wherein R is hydrogen or methyl and Y is carboxy or nitrile), a cross-linked dextrin, a cross-linked dextran, a cross-linked gum arabic , a cross-linked gelatin, a cross-linked alginic acid, a cross-linked polyacrylic acid and a copolymer of divinylbenzene with a monomer of the formula: CH 2 = C ( R 2 ) - X' (wherein R 2 is hydrogen or methyl and X' is carboxy or

Claim 7

The ethylcellulose microcapsules of Claim 1, in which said polymer material is selected from the class consisting of starch, crystalline cellulose, agar, alginic acid or its alkali earth metal salt, hydroxyprcpylstarch (hydroxypropyl content: 2 - 7 w/w%), hydroxypropylcellulose (hydroxypropyl content: 2 - 7 w/w%), carboxymethylcellulose or its alkali earth metal salt, starch-acrylic acid graft copolymer or its alkali metal salt, starch·acrylonitrile graft copolymer, cellulose.acrylic acid graft copolymer or its alkali metal salt, cellulose-acrylonitrile graft copolymer polyvinylalcohol·acrylic acid graft copolymer or its alkali metal salt, epichlorohydrin cross-linked dextran, epichlorohydrin cross-linked alginic acid, epichlorohydrin cross-linked polyvinylalcohol, formaldehyde cross-linked gelatin, acrylic acid cross-linked polyacrylic acid, divinylbenzene-acrylic acid copolymer or its alkali metal salt, divinylbenzene. methacrylic acid copolymer or its alkali metal salt and divinylbenzene-styrenesulfonic acid copolymer or its alkali metal salt.

Claim 8

The ethylcellulose microcapsules of Claim 1,2 3 or 4, in which said polymer material is incorporated into the ethylcellulose coating walls in an amount of not less than 0.01 gram per gram of ethylcellulose and/or into the core material in an amount of 3 to 99 w/w%.

Claim 9

The ethylcellulose microcapsules of Claim 1,2 3 or 4, in which said polymer material is incorporated into the ethylcellulose coating walls in an amount of 0.01 to 20 grams per gram of ethylcellulose and/or into the core materia in an amount of 3 to 90 w/w%.

Claim 10

The ethylcellulose microcapsules of Claim 1, 2, 3, 4, 5 or 6 in which the core material is a pharmaceutically active compound having a particle size of 30 - 1000 µ, ethylcellulose having an ethoxy content of 46.5 to 55 w/w % and a viscosity (measurcd at 25"C with respect to a 5 w/w % solution of it in toluene-ethanol (4 : 1)) of 3 to 500 cP is used, and the swellable polymer material having a particle size of 0.1 to 300 µ is used.

Claim 11

A process for preparing ethylcellulose microcapsules, which comprises the steps of: i) dissolving ethylcellulose in cyclohexane, ii) dispersing particles of a core material in said solution, iii) cooling the dispersion in the presence of a polymer material (said polymer mterial being the one which shows at least 1.2 times increase in weight by immersing it in water at 37°) until ethylcellulose separates out from the dispersion to form coating walls on and around the particles of the core material, and iv) recovering the resultant microcapsules therefrom.

Claim 12

A process for preparing ethylcellulose microcapsules, which comprises the steps of: i) dissolving ethylcellulose in cyclohexane, ii) dispersing particles of a core material in said solution, iii) cooling the dispersion in the presence of a polymer material (said polymer mterial being the one which shows at least 1.2 times increase in weight by immersing it in water at 37°) until ethylcellulose separates out from the dispersion to form coating walls on and around the particles of the core material, and iv) recovering the resultant microcapsules therefrom.

Claim 13

The process according to Claim 8, wherein said polymer material is selected from the class consisting of starch, crystalline cellulose, agar, hydroxy-lower alkyl-cellule hydroxy-lower alkyl-starch, carboxy-lower alkyl-cellulose, carboxy-lower alkyl-starch, carboxy-lower alkyl-cellulose, carboxy-lower alkyl-starch, carboxy-lower alkyl-celluloce carboxy-lower alkyl-starch or its alkali earth metal salt, a graft copolymer of starch, cellulose or polyvinylalcohol with a monomer of the formula: CH 2 = C(R 1 ) - Y' (wherein R 1 is hydrogen or methyl and Y is carboxy or nitrile), a cross-linked dextrin, a cross-linked dextran, a cross-linked gum arabic, a cross-linked gelatin, a cross-linked polyacrylic acid and a copolymer of divinylbenzene and a monomer of the formula: CH 2 = C(R 2 )-X' is hydrogen or methyl and X' is ! carbox y or

Claim 14

The process according to Claim 8, wherein said polymer material is selected from the class consisting of starch, crystalline cellulose, agar, hydroxy-propylstarch (hydroxyrropyl content: 2 - 7 w/w%), hydroxypropyl-cellulose (hydroxypropyl content: 2 - 7 w/w%), hydroxyropyl-cellulose (hydroxypropyl content: 2 - 7 w/w%), carboxymethylcellulose or its alkali earth metal salt, starch-acrylic acid graft copolymer or its alkali metal salt, starch·acrylonitrile graft copolymer, cellulose·acrylic acid graft copolymer or its alkali metal salt, cellulose.acrylonitrile graft copolymer, polyvinylalcohol·acrylic acid graft copolymer or its alkali - metal salt, epichlorohydrin cross-linked dextrin, epichlorohydrin cross-linked gum arabic, epichlorohydrin cross-linked dextran, epichlorohydrin cross-linked polyvinylalcohol, formaldehyde cross-linked gelatin, acrylic acid cross-linked polyacrylic acid, divinylbcnzene·acrylic acid copolymer cr its alkali metal salt, divinylbenzene·methacrylic acid copolymer or its alkali metal salt and divinylbenzene·styrenesulfonic acid copolymer or its alkali metal salt.

Claim 15

The process according to Claim 8, wherein ethylcellulose having an ethoxy content of 46.5 to 55 w/w% is used in an amount of 0.01 to 10 grams per gram of the core material, and the polymer material is used in an amount of not less than 0.1 gram per gram of ethylcellulose.

Claim 16

The process according to Claim 11, wherein the polymer material is used in an amount of 0.01 to 20 grams per gram of ethylcellulose.

Claim 17

The process according to Claim 8, 9 or 10, wherein the core material is a pharmaceutically active compound having a particle size of 30 - 1000 µ, ethylcellulose having an ethoxy content of 46.5 to 55 w/w % and a viscosity (measured at 25°C with respect to a 5 w/w% solution of it in toluene-ethanol (4 : 1)) of 3 to 500 cP is used in an amount of 0.01 to 10 gram per gram of the core material, and the polymer material having a particle size of 0.1 to 300 µ is used in an amount of 0.001 to 20 grams per gram of ethylcellulos

Claim 18

The process according to Claim 8, 9, 10 or 13, wherein at least one member selected from a phase-separation-inducing agent, an organosilicon polymer and a surfactant is further added to the solution of ethylcellulose.

Claim 19

A process for preparing ethylcellulose microcapsules, which comprises the steps of: i) dissolving ethylcellulose in cyclohexane, ii) dispersing, particles of a polymer material-containing core material (said polymer material being the one which shows at least 1.2 times increase in weight by immersing it in water at 37°C) in said solution, iii) cooling the dispersion until ethylcellulose separates out from the dispersion to form coating walls on and around the particles of the particles of the polymer material-containing core material, and iv) recovering the resultant microcapsules therefrom.

Claim 20

A process for preparing ethylcellulose microcapsules, which comprises the steps of: i) dissolving ethylcellulose in cyclohexane, ii) dispersing, particles of a polymer material-containing core material (said polymer material being the one which shows at least 1.2 times increase in weight by immersing it in water at 37°C) in said solution, iii) cooling the dispersion until ethylcellulose separates out from the dispersion to form coating walls on and around the particles of the particles of the polymer material-containing core material, and iv) recovering the resultant microcapsules therefrom.

Claim 21

The process according to Claim 15, wherein the dispersion is cooled in the presence of a polymer material which shows at least 1.2 times increase in weight by immersing it in water at 37°C.

Claim 22

The process according to Claim 15 or 16, wherein said polymer material is selected from the class consisting of starch, crystalline cellulose, agar, hydroxy-lower alkyl-cellulosc, hydroxy-lower alkyl-starch, carboxy-lower alkyl-cellulose, carboxy-lower alkyl-starch or its alkali earth metal salt, a graft copolymer of starch, cellulose or polyvinylalcohol with a monomer of the formula: CH 2 = C(R 1 ) - Y' (wherein R 1 is hydrogen or methyl and Y' is carboxy or nitrile), a cross-linked dextrin, a cross-linked dextran, a cross-linked gum arabic, a cross-linked gelatin, a cross-linked polyacrylic acid and a copolymer of divinylbenzene and a monomer of the formula: CH 2 = C(R 2 ) - X' (wherein R 2 is hydrogen or methyl and X' is carboxy or

Claim 25

The process according to Claim 15 or 16, wherein said polymer material is selected from the class consisting of starch, crystalline cellulose, agar, hydroxy- propylstarch (hydroxypropyl content: 2 - 7 w/w%), hydroxypropyl- cellulose (hydroxypropyl cntent: 2 - 7 w/w%), carboxymethyl- cellulose or its alkali earth metal salt, starch-acrylic acid graft copolymer or its alkali metal salt, starch·acrylonitrile graft copolymer, cellulose·acrylic acid graft copolymer or its alkali metal salt, cellulose·acrylonitrile graft copolymer, polyvinylalcohol·acrylic acid graft copolymer or its alkali metal salt, epichlorohydrin cross-linked dextrin, epichlorohydrin cross-linked gum arabic, epichlcrohydrin cross-linked dextran, epichlorohydrin cross-linked polyvinylalcohol, formaldehyde cress-linked gelatin, acrylic acid cross-linked polyacrylic acid, divinylbenzene·acrylic acid copolymer or its alkali metal salt, divinylbenzene-methacrylic acid copolymer or its alkali metal salt and divinylbenzene. styrenesulfonic acid copolymer or its alkali metal salt.

Claim 26

The process according to Claim 15 or 16, wherein ethylcellulose having an ethoxy content of 46.5 to 55 w/w% is used in an amount of 0.01 to 10 gram per gram of the core material, and the amount of the polymer material incorporated into the polymer material-containing core material is 3 to 99 w/w%.

Claim 27

The process according to Claim 19, wherein the dispersion is cooled in the presence of not less than 0.01 - gram (per gram of ethylcellulose) of the polymer material.

Claim 28

The process according to Claim 19, wherein the dispersion is cooled in the presence of 0.01 to 20 grams of the polymer material per gram of ethylcellulose.

Claim 29

The process according to Claim 15, 16, 18, 19 or 20, wherein at least one member selected from a phase- separaticn-inducing agent, an organosilicon polymer and a surfactant is further added to the solution of ethylcellulose.