Pharmaceutical compositions

• US 9,855,264 B2
• Filed: 09/12/2016
• Issued: 01/02/2018
• Est. Priority Date: 01/09/2008
• Status: Active Grant

• Current Assignee: LOCL Pharma, Inc. (Charleston Laboratories, Inc.)
• Original Assignee: LOCL Pharma, Inc. (Charleston Laboratories, Inc.)
• Inventors: Bosse, Paul, Ameling, John, Schachtel, Bernard, Takigiku, Ray
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US15/263,243
• Publication Number:
  US 20160375015A1
• Time in Patent Office: 477 Days
• Field of Search: None
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/24 having an amino or nitro group
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• 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 31/515 Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 : Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2086 : Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 : containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/4808 : characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5084 : Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 1/08 : for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 : without antiinflammatory effect
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

Methods and compositions are provided which comprise effective amounts of an analgesic to treat a subject, including reducing or eliminating an adverse effect associated with the analgesic.

Claims

1. A method for treating or preventing pain, and reducing or preventing opioid-induced nausea or vomiting, comprising administering to a subject in need thereof an immediate-release bi-layered tablet, wherein the immediate-release bi-layered tablet comprises:

a first layer, wherein the first layer comprises;

an antiemetic that is promethazine or a pharmaceutically acceptable salt thereof, and one or more of silicified microcrystalline cellulose, croscarmellose sodium, or magnesium stearate; and

a second layer, wherein the second layer comprises;

an opioid analgesic that is hydrocodone or a pharmaceutically acceptable salt thereof and is not conjugated to a peptide, a non-opioid analgesic that is acetaminophen or a pharmaceutically acceptable salt thereof, and hydroxypropyl methylcellulose,

wherein the immediate-release bi-layered tablet provides an effective amount of the opioid analgesic and the non-opioid analgesic to treat or prevent pain in the subject, and wherein the immediate-release bi-layered tablet provides an effective amount of the antiemetic to reduce or prevent nausea associated with the opioid analgesic or reduce or prevent vomiting associated with the opioid analgesic, in the subject.

2. The method of claim 1, wherein the method treats pain and reduces opioid-induced vomiting.

3. The method of claim 1, wherein the method treats pain and reduces opioid-induced nausea.

4. The method of claim 1, wherein the method treats pain and reduces opioid-induced nausea and vomiting.

5. The method of claim 1, wherein the subject has a reduction in incidence of nausea or vomiting.

6. The method of claim 1, wherein the subject has a reduction in intensity of nausea or vomiting.

7. The method of claim 1, wherein the pain is severe.

8. The method of claim 1, wherein the antiemetic is promethazine hydrochloride.

9. The method of claim 1, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount from 5 mg to 30 mg.

10. The method of claim 9, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount from 5 mg to 13 mg.

11. The method of claim 10, wherein the promethazine or the pharmaceutically acceptable salt thereof is present in an amount of about 12.5 mg.

12. The method of claim 1, wherein the opioid analgesic is hydrocodone bitartrate.

13. The method of claim 1, wherein the hydrocodone or the pharmaceutically acceptable salt thereof is present in an amount from about 0.5 mg to about 20 mg.

14. The method of claim 13, wherein the hydrocodone or the pharmaceutically acceptable salt thereof is present in an amount from 6 mg to 8 mg.

15. The method of claim 14, wherein the hydrocodone or the pharmaceutically acceptable salt thereof is present in an amount of about 7.5 mg.

16. The method of claim 1, wherein the acetaminophen or the pharmaceutically acceptable salt thereof is present in an amount from about 200 mg to about 1000 mg.

17. The method of claim 16, wherein the acetaminophen or the pharmaceutically acceptable salt thereof is present in an amount from 310 mg to 330 mg.

18. The method of claim 17, wherein the acetaminophen or the pharmaceutically acceptable salt thereof is present in an amount of about 325 mg.

19. The method of claim 1, wherein the hydrocodone or the pharmaceutically acceptable salt thereof, the acetaminophen or the pharmaceutically acceptable salt thereof, and the promethazine or the pharmaceutically acceptable salt thereof are present in an amount of 6 mg to 8 mg, 310 mg to 330 mg, and 5 mg to 13 mg, respectively.

20. The method of claim 19, wherein the hydrocodone or the pharmaceutically acceptable salt thereof, the acetaminophen or the pharmaceutically acceptable salt thereof, and the promethazine or the pharmaceutically acceptable salt thereof are present in an amount of about 7.5 mg, about 325 mg, and about 12.5 mg, respectively.

21. The method of claim 1, wherein the method is for treatment of pain and reduction of opioid-induced nausea and vomiting, wherein the antiemetic is promethazine hydrochloride, wherein the opioid analgesic is hydrocodone bitartrate, and wherein the non-opioid analgesic is acetaminophen.

22. The method of claim 1, wherein the method is for treatment of pain and reduction of opioid-induced nausea and vomiting, wherein the antiemetic is promethazine hydrochloride and present in an amount of about 12.5 mg, wherein the opioid analgesic is hydrocodone bitartrate and present in an amount of about 7.5 mg, and wherein the non-opioid analgesic is acetaminophen and present in an amount of about 325 mg.

23. The method of claim 1, wherein the immediate-release bi-layered tablet further comprises an opioid antagonist or an abuse deterrent agent.

27. The method of claim 1, wherein the administering to the subject in need therefor occurs at about every 4, 5, or 6 hours.

24. A method for treating or preventing pain, and reducing or preventing opioid-induced nausea or vomiting, comprising administering to a subject in need thereof an immediate-release bi-layered tablet, wherein the immediate-release bi-layered tablet comprises:

a first layer, wherein the first layer comprises;

an antiemetic that is promethazine or a pharmaceutically acceptable salt thereof, silicified microcrystalline cellulose, croscarmellose sodium, and magnesium stearate; and

a second layer, wherein the second layer comprises;

an opioid analgesic that is hydrocodone or a pharmaceutically acceptable salt thereof and is not conjugated to a peptide, and a non-opioid analgesic that is acetaminophen or a pharmaceutically acceptable salt thereof,

wherein the immediate-release bi-layered tablet provides an effective amount of the opioid analgesic and the non-opioid analgesic to treat or prevent pain in the subject, and wherein the immediate-release bi-layered tablet contains an effective amount of the antiemetic to reduce or prevent nausea associated with the opioid analgesic or reduce or prevent vomiting associated with the opioid analgesic, in the subject.

28. The method of claim 24, wherein the administering to the subject in need thereof occurs at about every 4, 5, or 6 hours.

25. A method for treating or preventing pain, and reducing or preventing opioid-induced nausea or vomiting, comprising administering to a subject in need thereof an immediate-release bi-layered tablet, wherein the immediate-release bi-layered tablet comprises:

a first layer, wherein the first layer comprises;

an antiemetic that is promethazine or a pharmaceutically acceptable salt thereof; and

a second layer, wherein the second layer comprises;

an opioid analgesic that is hydrocodone or a pharmaceutically acceptable salt thereof and is not conjugated to a peptide, a non-opioid analgesic that is acetaminophen or a pharmaceutically acceptable salt thereof, silicified microcrystalline cellulose, hydroxypropyl methylcellulose, magnesium stearate, and stearic acid,

wherein the immediate-release bi-layered tablet provides an effective amount of the opioid analgesic and the non-opioid analgesic to treat or prevent pain in the subject, and wherein the immediate-release bi-layered tablet provides an effective amount of the antiemetic to reduce or prevent nausea associated with the opioid analgesic or reduce or prevent vomiting associated with the opioid analgesic, in the subject.

29. The method of claim 25, wherein the administering to the subject in need thereof occurs at about every 4, 5, or 6 hours.

26. An immediate-release bi-layered tablet for treatment or prevention of pain, and reduction or prevention of opioid-induced nausea or vomiting, wherein the immediate-release bi-layered tablet comprises:

a first layer, wherein the first layer comprises;

an antiemetic that is promethazine or a pharmaceutically acceptable salt thereof, silicified microcrystalline cellulose, croscarmellose sodium, and magnesium stearate; and

a second layer, wherein the second layer comprises;

an opioid analgesic that is hydrocodone or a pharmaceutically acceptable salt thereof and is not conjugated to a peptide, a non-opioid analgesic that is acetaminophen or a pharmaceutically acceptable salt thereof, silicified microcrystalline cellulose, hydroxypropyl methylcellulose, magnesium stearate, and stearic acid,

wherein the immediate-release bi-layered tablet provides an effective amount of the opioid analgesic and the non-opioid analgesic to treat or prevent pain, and wherein the immediate-release bi-layered tablet contains an effective amount of the antiemetic to reduce or prevent nausea associated with the opioid analgesic or reduce or prevent vomiting associated with the opioid analgesic.

30. The immediate-release bi-layered tablet of claim 26, wherein the immediate-release bi-layered tablet is for administration at about every 4, 5, or 6 hours.