Methods and devices for delivering opioid analgesics to wounds via a subdermal implant

• US 5,919,473 A
• Filed: 05/12/1997
• Issued: 07/06/1999
• Est. Priority Date: 05/12/1997
• Status: Expired due to Term

• Current Assignee: George F. Elkhoury
• Original Assignee: George F. Elkhoury
• Inventors: Elkhoury, George F.
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/854,323
• Time in Patent Office: 785 Days
• Field of Search: 424/443, 424/444, 424/422, 424/423, 424/426, 606/228, 606/229, 606/230
• US Class Current: 424/422
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/451 having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 17/005 containing a biologically active substance, e.g. a medicament or a biocide
• CPC Class Codes: A61L 2300/402 Anaestetics, analgesics, e.g. lidocaine
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

An analgesic agent delivery system and method of treating postoperative pain comprising an analgesic agent such as morphine and an extended-release drug delivery device. The device may be placed in the vicinity of a wound and then provide an extended-release of the analgesic agent over a period of time, thereby controlling the pain emanating from the wound.

Claims

1. A method of inducing analgesia, comprising delivering, for a period of time which is at least about 1 day, via a surgical suture, a therapeutically-effective amount of an opioid analgesic agent to peripheral opioid receptors, which amount is ineffective for the production of centrally-mediated analgesia.

2. The method of claim 1, wherein said suture comprises a polymeric material.

3. The method of claim 1, wherein said suture comprises an absorbable material.

4. The method of claim 3, wherein said absorbable material comprises a synthetic material.

5. The method of claim 4, wherein said synthetic material is selected from the group consisting of cellulosic polymers, glycolic acid polymers, methacrylate polymers, ethylene vinyl acetate polymers, ethylene vinyl alcohol copolymers, polycaptrolactam, polyacetate, copolymers of lactide and glycolide, polydioxanone, polyglactin, poliglecaprone, polyglyconate, polygluconate, and combinations thereof.

6. The method of claim 3, wherein said absorbable material comprises a non-synthetic material.

7. The method of claim 6, wherein said non-synthetic material is selected from the group consisting of catgut, cargile membrane, fascia lata, gelatin, collagen, and combinations thereof.

8. The method of claim 1, wherein said suture comprises a nonabsorbable material.

9. The method of claim 8, wherein said nonabsorbable material comprises a synthetic material.

10. The method of claim 9, wherein said synthetic material is selected from the group consisting of nylons, rayons, polyesters, polyolefins, and combinations thereof.

11. The method of claim 8, wherein said nonabsorbable material comprises a non-synthetic material.

12. The method of claim 11, wherein said non-synthetic material is selected from the group consisting of silk, dermal silk, cotton, linen, and combinations thereof.

13. A method of inducing analgesia, comprising delivering, for a period of time which is at least about 1 day, via an at least partially subdermal drug delivery device, a therapeutically-effective amount of an opioid analgesic agent to peripheral opioid receptors, which amount is ineffective for the production of centrally-mediated analgesia, wherein said device comprises staples or clips.

14. A method of inducing analgesia, comprising delivering, for a period of time which is at least about 1 day, via an at least partially subdermal drug delivery device, a therapeutically-effective amount of an opioid analgesic agent to peripheral opioid receptors, which amount is ineffective for the production of centrally-mediated analgesia, wherein said device is selected from the group consisting of trocars, catheters, and tubes.

15. A drug delivery device for subdermal administration comprising an opioid agonist selected from the group consisting of morphine, depomorphine, heroin, oxymorphone, levorphanol, methadone, meperidine, fentanyl, sufentanil, alfentanil, codeine, hydrocodone, drocode, oxycodone, and mixtures thereof, and a polymeric material, which device releases said opioid analgesic for a period of time which is at least about 1 day, and wherein a unit dosage of the device does not contain enough opioid analgesic agent to produce centrally-mediated analgesia.

16. A drug delivery device for subdermal administration comprising an opioid analgesic and a polymeric material, which device releases said opioid analgesic for a period of time which is at least about 1 day, wherein a unit dosage of the device does not contain enough opioid analgesic agent to produce centrally-mediated analgesia, and wherein said opioid analgesic comprises a partial opioid agonist.

17. The device of claim 16, wherein said partial opioid agonist comprises ethylketocyclazocine.

18. A drug delivery device for subdermal administration comprising an opioid analgesic and a polymeric material, which device releases said opioid analgesic for a period of time which is at least about 1 day, wherein a unit dosage of the device does not contain enough opioid analgesic agent to produce centrally-mediated analgesia, and wherein said opioid analgesic comprises a mixed opioid agonist/antagonist.

19. The device of claim 18, wherein said mixed opioid agonist/antagonist is selected from the group consisting of cyclazocine, nalbuphine, buprenorphine, meptazinol, butorphanol, pentazocine, dezocine, and mixtures thereof.

20. A drug delivery device for subdermal administration comprising an opioid analgesic and a polymeric material, which device releases said opioid analgesic for a period of time which is at least about 1 day, wherein a unit dosage of the device does not contain enough opioid analgesic agent to produce centrally-mediated analgesia, and wherein said polymeric material comprises an absorbable material.

21. The device of claim 20, wherein said absorbable material comprises a synthetic material.

22. The device of claim 21, wherein said synthetic material is selected from the group consisting of polyglycolic acid, copolymers of lactide and glycolide, polydioxanone, polyglactin, poliglecaprone, polyglyconate, polygluconate, and combinations thereof.

23. The device of claim 20, wherein said absorbable material comprises a non-synthetic material.

24. The device of claim 23, wherein said non-synthetic material is selected from the group consisting of gelatin, collagen, and combinations thereof.

28. The device of claim 20, wherein the opioid analgesic agent comprises up to 90% by weight of the device.

29. The device of claim 28, wherein the opioid analgesic agent comprises up to 70% by weight of the device.

30. The device of claim 29, wherein the opioid analgesic agent comprises up to 30% by weight of the device.

25. A drug delivery device for subdermal administration comprising an opioid analgesic selected from the group consisting of morphine, depomorphine, heroin, oxymorphone, levorphanol, methadone, meperidine, fentanyl, sufentanil, alfentanil, codeine, hydrocodone, drocode, oxycodone, and mixtures thereof, and a polymeric material, which device releases said opioid analgesic for a period of time which is at least about 1 day, wherein a unit dosage of the device does not contain enough opioid analgesic agent to produce centrally-mediated analgesia, and wherein a unit dosage is eguianalgesic to from about 0.01 mg morphine/4 hr/10 cm wound to about 8 mg morphine/4 hr/10 cm wound.

26. The device of claim 25, wherein a unit dosage is equianalgesic to from about 2 mg morphine/4 hr/10 cm wound to about 6 mg morphine/4 hr/10 cm wound.

27. The device of claim 26, wherein a unit dosage is equianalgesic to about 4 mg morphine/4 hr/10 cm wound.