Dispenser comprising ionophore

• US 5,126,142 A
• Filed: 01/11/1991
• Issued: 06/30/1992
• Est. Priority Date: 07/18/1989
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Burkoth, Terry L., Ayer, Atul D., Kuczynski, Anthony L., Deters, Joseph C.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HORNE, LEON
• Application Number:
  US07/641,023
• Time in Patent Office: 536 Days
• Field of Search: 424/438, 424/473, 424/422
• US Class Current: 424/439
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0068 Rumen, e.g. rumen bolus

Abstract

A dispenser is disclosed for delivering a beneficial ionophore to an animal. The dispenser comprises (1) a semipermeable housing defining an internal space, (2) at least one composition comprising an ionophore and a pharmaceutically acceptable carrier in the space, (3) an expandable hydrophilic composition in the space, (4) a dense member in the space, and (5) at least one exit passageway in the housing for delivering the ionophore from the dispenser.

Claims

1. A dispenser for delivering a beneficial ionophore to a fluid environment of use, the dispenser comprising:

(a) a wall comprising in at least a part a semipermeable composition permeable to the passage of fluid and substantially impermeable to the passage of an ionophore, which wall surrounds

(b) a compartment;

(c) a composition in the compartment comprising an ionophore and a pharmaceutically acceptable carrier for the ionophore;

(d) a hydrophilic polymeric composition in the compartment that expands in the presence of fluid for pushing the composition comprising the ionophore from the dispenser;

(e) a densifier in the compartment, the densifier having a specific gravity greater than the specific gravity of fluid present in the environment of use; and

(f) an exit passageway or multiplicity of exit passageways in the wall for delivering a therapeutically effective amount of the ionophore from the dispenser over a period of time, the diameter of each exit passageway being of a size to maximize release of the ionophore by osmotic pumping and minimum the release of the ionophore by diffusion to avoid mechanical agitation-dependent ionophore release.

2. A dispenser according to claim 1 wherein the ionophore is lysocellin.

3. A dispenser according to claim 1 wherein the ionophore is tetronasin.

4. A dispenser according to claim 1 wherein the ionophore is a member selected from the group consisting of lonomycin, lenotemycin, erythromycin, isolasalocid, laidlomycin, laidlomycin propionate, laidlomycin butyrate, semduramicin, alborixin, lasalocid, septamycin, nigericin, dianemycin, monensin, and salinomycin, and pharmaceutically acceptable salts and esters thereof.

5. A dispenser according to claim 1 wherein the dispenser delivers the ionophore for about 150 days.

21. A dispenser according to claim 4 wherein the ionophore is laidlomycin propionate.

6. A dispenser for delivering a beneficial ionophore to a fluid environment of use, the dispenser comprising:

(a) a wall comprising in at least a part a nontoxic composition permeable to the passage of fluid and substantially impermeable to the passage of an ionophore, the wall surrounding and forming

(b) a compartment;

(c) a composition in the compartment comprising an ionophore and a pharmaceutically acceptable carrier for the ionophore;

(d) a second composition in the compartment comprising an ionophore and a pharmaceutically acceptable carrier for the ionophore;

(e) a hydrophilic polymeric composition in the compartment comprising an osmotic composition that expands when contacted by fluid to displace the first and second compositions from the dispenser;

(f) a densifier in the compartment, the densifier having a specific gravity greater than the specific gravity of fluid present in the environment of use; and

(g) an exit passageway or multiplicity of exit passageways in the wall for delivering the first and second compositions from the dispenser in therapeutically effective amounts over a period of time, the diameter of each exit passageway being of a size to maximize release of the ionophore by osmotic pumping and minimum the release of the ionophore by diffusion to avoid mechanical agitation-dependent ionophore release.

7. A dispenser according to claim 6 wherein the ionophore in the first composition is lysocellin or tetronasin.

8. A dispenser according to claim 6 wherein the ionophore in the second composition is lysocellin or tetronasin.

9. A dispenser according to claim 6 wherein the first composition and the second composition comprise the same ionophore.

10. A dispenser according to claim 9 wherein the ionophore is lysocellin or tetronasin.

11. A dispenser according to claim 6 wherein the first composition and the second composition comprise different ionophores.

12. A dispenser according to claim 6 wherein the dispenser delivers an ionophore for about 150 days.

13. A dispenser according to claim 6 wherein the ionophore in the first composition comprises an ionophore selected from the group consisting of valinomycin, enniactin, monactin, nonactin, dinactin, trinactin, virginiamycin, tetronasin, semduramicin, monensin, monensin sodium, nigericin, narasin, salinomycin, isolasalocid, lasalocid, lysocellin, septamycin, laidlomycin, laidlomycin propionate, laidlomycin butyrate, lonomycin, lenotemycin, grisorixin, alborixin, erythromycin, azolomycin, and sodium lysocellin, and pharmaceutically acceptable salts and esters thereof.

14. A dispenser according to claim 6 wherein the ionophore in the second composition comprises a member selected from the group consisting of valinomycin, enniactin, monactin, nonactin, dinactin, trinactin, virginiamycin, tetronasin, semduramicin, monensin, monensin sodium, nigericin, narasin, salinomycin, isolasalocid, lasalocid, lysocellin, septamycin, laidlomycin, laidlomycin propionate, laidlomycin butyrate, lonomycin, lenotemycin, grisorixin, alborixin, erythromycin, azolomycin, and sodium lysocellin, and pharmaceutically acceptable salts and esters thereof.

15. A dispenser according to claim 6 which further comprises a third composition in the compartment comprising an ionophore and a pharmaceutically acceptable carrier for the ionophore.

16. A dispenser according to claim 15 wherein the ionophore in the third composition comprises a member selected from the group consisting of valinomycin, enniactin, monactin, nonactin, dinactin, trinactin, virginiamycin, tetronasin, semduramicin, monensin, monensin sodium, nigericin, narasin, salinomycin, isolasalocid, lasalocid, lysocellin, septamycin, laidlomycin, laidlomycin propionate, laidlomycin butyrate, lonomycin, lenotemycin, grisorixin, alborixin, erythromycin, azolomycin, and sodium lysocellin, and pharmaceutically acceptable salts and esters thereof.

22. A dispenser according to claim 9 wherein the ionophore is laidlomycin propionate.

17. A composition for dispensing an ionophore from a drug delivery dispenser to livestock over a prolonged period of time, said composition comprising 10 mg to 100 g of an ionophore selected from the group consisting of valinomycin, enniactin, monactin, nonactin, dinactin, trinactin, virginiamycin, tetronasin, semduramicin, monensin, monensin sodium, nigericin, narasin, salinomycin, isolasalocid, lasalocid, lysocellin, septamycin, laidlomycin, laidlomycin propionate, laidlomycin butyrate, lonomycin, lenotemycin, grisorixin, alborixin, erythromycin, azolomycin, and sodium lysocellin, and pharmaceutically acceptable salts and esters thereof;

and a pharmaceutically acceptable poly(ethylene oxide) carrier comprising a 200,000 to 7,500,000 molecular weight.

18. A composition according to claim 17 wherein the ionophore is lysocellin, laidlomycin propionate or tetronasin.

19. A method for administering to an animal a biologically active ionophore, said method comprising:

(A) admitting orally into the animal a dispenser comprising;

(1) a wall that surrounds and forms an internal compartment, the wall comprising in at least a part a composition permeable to the passage of fluid and substantially impermeable to the passage of an ionophore;

(2) a composition in the compartment comprising a biologically active ionophore selected from the group consisting of valinomycin, enniactin, monactin, nonactin, dinactin, trinactin, virginiamycin, tetronasin, semduramicin, monensin, monensin sodium, nigericin, narasin, salinomycin, isolasalocid, lasalocid, lysocellin, septamycin, laidlomycin, laidlomycin propionate, laidlomycin butyrate, lonomycin, lenotemycin, grisorixin, alborixin, erythromycin, azolomycin, and sodium lysocellin, and pharmaceutically acceptable salts and esters thereof; and

a pharmaceutically acceptable carrier for the ionophore, said carrier comprising a poly(ethylene oxide) comprising up to 90 wt % of the ionophore;

(3) a hydrophilic composition in the compartment that expands when contacted by fluid, thereby experting pressure against the ionophore composition for displacement of the ionophore composition from the compartment;

(4) a densifier in the compartment for maintaining the dispenser in the animal over time, the densifier having a density greater than the density of the fluid present in the animal; and

(5) an exit passageway or multiplicity of exit passageways in the wall for delivering the biologically active ionophore from the dispenser, the diameter of each exit passageway being of a size to maximize release of the ionophore by osmotic pumping and minimum the release of the ionophore by diffusion to avoid mechanical agitation-dependent ionophore release; and

(B) administering the biologically active ionophore by the ionophore composition absorbing fluid to form a dispensable composition and by the hydrophilic composition absorbing fluid, expanding and displacing the ionophore composition through the passageway or passageways in a therapeutically effective amount to the animal at a controlled rate over time.

20. A method according to claim 19 wherein the ionophore is lysocellin, laidlomycin propionate or tetronasin.