Implantable delivery dispenser

• US 5,112,614 A
• Filed: 09/14/1989
• Issued: 05/12/1992
• Est. Priority Date: 09/14/1989
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Magruder, Judy A., Eckenhoff, James B., Wright, Jeremy C.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Webman, Edward J.
• Application Number:
  US07/407,489
• Time in Patent Office: 971 Days
• Field of Search: 424/422, 424/424, 424/425, 424/426, 424/428, 424/486, 424/498, 424/502
• US Class Current: 424/422
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

An implantable dispenser is enclosed comprising a wall surrounding a compartment containing a first composition comprising a beneficial agent, an oil, a cosolvent and a polymer gellant, a second expandable composition, a third boundary maintaining composition between the first and second composition, and an exit port.

Claims

1. An improvement in an implantable dispenser for delivering a beneficial agent to an animal, the implantable dispenser comprising:

(a) a wall in at least a part comprising a composition permeable to the passage of fluid, which wall surrounds;

(b) an internal lumen;

(c) a composition when contacted by fluid increases in volume for displacing a formulation from the implantable dispenser; and

,

(d) an exit port in the wall that connects the exterior of the implantable dispenser with the lumen, and wherein the improvement comprises;

(e) a pharmaceutically acceptable beneficial agent formulation in the lumen, which formulation comprises (1) a beneficial agent;

(2) an oil that is a carrier for the agent; and

(3) a polymer that imparts gel properties to the oil, whereby, through the combined operations of (a), (c), (d) and (e) the beneficial agent formulation is delivered at a rate controlled by the implantable dispenser to the animal over time.

2. The improvement in an implantable dispenser for delivering a beneficial agent according to claim 1, wherein the polymer that imparts gelation comprises a member selected from the group consisting of olefin, condensation and addition polymers.

3. The improvement in an implantable dispenser for delivering a beneficial agent according to claim 1, wherein the polymer that comprises gelation comprises a member selected from the group consisting of ethylene-vinyl ester copolymer comprising a vinyl acetate content of 4% to 80%.

4. The improvement in an implantable dispenser for delivering a beneficial agent according to claim 1, wherein the beneficial agent is a member selected from the group consisting of dromostanolone, dromostanolone propionate, chlormadinone, chlormadinone acetate, melengestrol acetate, norgestomet, dimethisterone, ethisterone, hydroxyprogesterone, estradiol, 17α

-acetoxy-11β

-methyl-19-norpregn-4-ene-3,20-dione, 3(3-oxo-11β

,13β

-dialkyl-17β

-hydroxygon-4-en-17α

-yl) propionic acid-lactone, 3(3-oxo-11β

methyl-1762 -hydroxyestr-4-en-17α

-yl) propionic acid lactone, 11,13β

-dialkyl-17-lower alkyl-gon-4-en-3-one, and 19-norpregn-4-ene-3,20-dione.

5. The implantable dispenser for delivering the beneficial agent to an animal according to claim 1, wherein the beneficial agent comprises a member selected from the group consisting of oxytocin, vasopressin, adrenocorticotropic, prolactin, luliberin, luteinizing hormone, insulin, somatostatin, glucagon, interferon, gastrin, tetragastrin, pentagastrin, urogastrone, secretin, calcitonin, endorphin, angiotensin, renin, bradykinin, bacitracin, polymyxin, colistin, tyrocidine and gramicidins.

6. The implantable dispenser for delivering the beneficial agent to an animal according to claim 1, wherein the beneficial agent is a member selected from the group consisting of monoclonal antibody, vaccine, somatotropin, cosyntropin, gonadotropin, thyrotropin releasing hormone, thyroid stimulating hormone, and pancreozymin.

7. The implantable dispenser for delivering a beneficial agent to an animal according to claim 1, wherein a coat is on the exterior surface of the wall, said coat a means for governing the volume of external fluid that enters the implantable dispenser.

8. An implantable dispenser for delivering a beneficial agent to an animal, the implantable dispenser comprising:

(a) a wall in at least a part comprising a semipermeable composition;

(b) an internal lumen;

(c) a composition that increases in volume when contacted by fluid in the lumen and thereby aids in pushing a beneficial agent formulation from the implantable dispenser; and

,

(d) an exit port in the wall that connects the exterior of the implantable dispenser with the lumen, the implantable dispenser characterized by;

(e) a pharmaceutically acceptable formulation in the lumen, the formulation comprising (1) a beneficial agent for delivering to an animal;

(2) a nontoxic oil carrier for the beneficial agent;

(3) a nontoxic cosolvent for increasing the amount of beneficial agent present in the oil carrier; and

(4) a nontoxic polymer gellant for the oil, whereby, through the operations of (a), (c), (d) and (e) the beneficial agent is delivered at a rate controlled by the implantable dispenser to the animal over time.

9. The implantable dispenser for delivering a beneficial agent to an animal according to claim 8, wherein a composition comprising means for maintaining the integrity of both the composition that increases in volume and the pharmaceutically acceptable formulation is positioned therebetween.

10. The implantable dispenser for delivering a beneficial agent to an animal according to claim 8, wherein the composition that increases in volume comprises a hydrogel.

11. The implantable dispenser for delivering a beneficial agent to an animal according to claim 8, wherein the composition that increases in volume comprises an osmagent.

12. The implant dispenser for delivering a beneficial agent to an animal according to claim 8, wherein a coat is on the exterior surface of the wall, said coat a means for governing the volume of external fluid that enters the implantable dispenser.

13. The implantable dispenser for delivering the beneficial agent to an animal according to claim 8, wherein the beneficial agent comprises a member selected from the group consisting of oxytocin, vasopressin, adrenocorticotropic, prolactin, luliberin, luteinizing hormone, insulin, somatostatin, glucagon, interferon, gastrin, tetragastrin, pentagastrin, urogastrone, secretin, calcitonin, enkephalin, endorphin, angiotensin, renin, bradykinin, bacitracin, polymyxin, colistin, tyrocidin and gramicidins.

14. The implantable dispenser for delivering the beneficial agent to an animal according to claim 8, wherein the beneficial agent is a member selected from the group consisting of monoclonal antibody, vaccine, somatotropin, cosyntropin, gonadotropin, thyrotropin releasing hormone, thyroid stimulating hormone, and pancreozymin.

15. The implantable dispenser for delivering the beneficial agent to an animal according to claim 8, wherein the exit port is formed by fluid removing a port forming composition from the dispenser.

16. The implantable dispenser for delivering the beneficial agent to an animal according to claim 8, wherein the implantable dispenser comprises more than one exit port.

17. The implantable dispenser for delivering the beneficial agent to an animal according to claim 8, wherein the polymer gellant comprises a member selected from the group consisting of ethylenevinyl formate copolymer, ethylene-vinyl acetate copolymer, ethylenevinyl hexanoate copolymer, ethylene-vinyl propionate copolymer, ethylene-vinyl pentanoate copolymer, ethylene-vinyl isopropylate copolymer, ethylene-vinyl diacetate copolymer, ethylene-vinyl tertbutylacetate copolymer, ethylene-vinyl phenylacetate copolymer and ethylene-vinyl benzoate copolymer.

18. The implantable dispenser for delivering the beneficial agent to an animal according to claim 8, wherein the cosolvent comprises a member selected from the group consisting of butyl stearate, stearyl stearate, propyl stearate, isopropyl stearate, 2-ethylhexyl stearate, myristyl stearate, decyl stearate, benzyl stearate, butyl palmitate, cetyl palmitate, 2-ethylhexyl palmitate, isopropyl palmitate, butyl alurate, isopropyl laurate hexyl laurate, cetyl laurate, isopropyl myristate, butyl myristate, myristyl myristate, lauryl myristate, isoamyl myristate, decyl oleate, di-isopropyl adipate, di-2-ethylhexyl adipate, di-n-butyl sebacate, di-2-ethylhexyl sebacate, di-isopropyl sebacate, isopropyl linoleate, cetyl lactate, lauryl lactate, myristyl lactate, decyl oleate, and isodecyl oleate.

19. The implantable dispenser for delivering the beneficial agent to an animal according to claim 8, wherein the polymer gellant comprises a member selected from the group consisting of olefin polymers, condensation polymers, addition polymers, cellulosic polymers, saccharide polymers, and organo-silicon polymers.