CA2452872A1 - Parenteral administration of 6-hydroxy-oxymorphone for use as an analgesic - Google Patents
Parenteral administration of 6-hydroxy-oxymorphone for use as an analgesic Download PDFInfo
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- CA2452872A1 CA2452872A1 CA002452872A CA2452872A CA2452872A1 CA 2452872 A1 CA2452872 A1 CA 2452872A1 CA 002452872 A CA002452872 A CA 002452872A CA 2452872 A CA2452872 A CA 2452872A CA 2452872 A1 CA2452872 A1 CA 2452872A1
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- Prior art keywords
- oxymorphone
- hydroxy
- pharmaceutical composition
- administration
- hydroxy oxymorphone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
In a method of treating pain a patient is administered a pharmaceutical composition of 6-hydroxy oxymorphone in an amount sufficient to induce analgesia. In one embodiment,the pharmaceutical composition is administered parenterally, preferably by injection and intravenous drip. To achieve the desired analgesic effect, blood plasma levels of 6-hydroxy oxymorphone are raised to at least approximately 0.05 ng/mL during treatment. Administration of compositions containing 6-hidroxy oxymorphone, and one or more carriers, diluents, and excipients in an amount sufficient to induce analgesia is also contemplated.
Description
FOR USE AS AN ANALGESIC
s This application relates to provisional patent application serial nos.
60/329,445 filed October 15, 2001, 60/329,432 filed October 15, 2001, 60/303,357 filed July 6, 2001, and 60/329,444 filed October 15, 2001.
1 o Background Field of Invention The invention relates to methods for alleviating pain. More particularly, the invention relates to methods for alleviating pain by administering 6-hydroxy oxymorphone. Most particularly, the invention relates to methods of inducing analgesia ~ s by increasing blood plasma levels of 6-hydroxy oxyrnorphone.
Summary of the Invention The present invention provides methods for treating pain by administration of a pharmaceutical composition comprising 6-hydroxy oxymorphone in an amount sufficient 2o to induce analgesia. In one embodiment, the pharmaceutical composition is administered parenterally, preferably by injection and intravenous drip. To achieve the desired analgesic effect, blood plasma levels of 6-hydroxy oxymorphone are raised to at least approximately 0.05 ng/mL. Methods for administering compositions comprising 6-hydroxy oxymorphone, and one or more carriers, diluents, and excipients in an amount 2s sufficient to induce analgesia are also provided.
Brief Description of the Drawings Fig. 1 is a pharmacokinetic profile for 6-hydroxy oXymorphone with PID scores.
Fig. 2 is a pharmacokinetic profile for oxymorphone with PID scores.
so Fig. 3 is a pharmacokinetic profile for 6-hydroxy oxymorphone with categorical pain scores.
Fig. 4 is a pharmacokinetic profile for oxymorphone with categorical pain scores.
Detailed Description The methods described herein provide for the direct administration of a pharmaceutical composition containing 6-hydroxy oxymorphone as an active ingredient.
s In a preferred embodiment the composition comprising 6-hydroxy oxymorphone alone (excepting, of course, carriers, diluents, and other excipients), In other embodiments, 6-hydorxy oxymorphone may be combined with other opioids or other pharmaceutical agents. For example compositions comprising both 6-hydroxy oxymorphone and its parent, oxymorphone.
io In separate studies, blood plasma levels and indications of pain relief were recorded over a 12 hour period. Figs. 1-4 show graphical representation of the data combining the two studies such that the effect of blood plasma levels on pain can be evaluated.
The administration of oxyrnoiphone yields blood plasma levels of oxymorphone i s and one of its metabolites, 6-hydroxy oxymorphone. Oxymorphone levels peak within 2 hours, fall slightly, and plateau. Interestingly, the level spikes again at 4-6 hours from administration. After this time, oxymorphone levels again drop and eventually fall to levels near the earlier plateau.
Like oxymorphone, 6-hydroxy oxyrnorphone blood plasma levels peak within 2 2o hours after administration. After the initial peak, however, a more or less steady decline in the 6-hydroxy oxymorphone's plasma levels is observed.
Comparing these levels to the pain profiles, a coiTelation between the 6-hydroxy oxyrnorphone blood plasma levels and pain relief can be seen. The pain levels nearly mirror the 6-hydroxy oxyrnorphone levels, with substantial rises in relief near the spikes 2s associated with oxymorphone blood levels. Thus, pain relief can be achieved through administration of 6-hydroxy oxymorphone alone.
In addition to the pharmacol~inetic studies, binding studies have been conducted to compare the binding affinity of 6-hydroxy oxymorphone to that of oxymorphone.
The results are reported in TABLE 1. These results clearly indicate that 6-hydroxy so oxymorphone has great binding affinity for the 8, k and p,, receptor cites, comparable to the binding affinity of its parent. The inventors believe that by virtue of this binding affinity, 6-hydroxy oxymorphone has similar analgesic effects to its parent, oxyrnorphone.
TABLE 1: ASSAY REPORT
s OXYMORPHONE
lOnm lOp,m lOnm lOpm 1.0 1.0 E-5 1.0 E-8 1.0 E-5 Opiate, Delta-4.12% 90.48% -18.26% 89.03%
Opiate, Delta7.19% 55.45% 7.76% 72.74%
2 (Human Recombinant) Opiate, 2.45% 62.47% 10.35% 89.41%
Kappa (Human Recombinant) Opiate, Mu 63.16% 99.91% 85.42% 100.39%
(Human Recombinant) Accordingly, methods of administering the metabolite, 6-hydroxy oxymorphone, directly have been developed. It is believed that the ~ isomer has greater efficacy in the treatment of pain, but this disclosure is not limited to use of that isomer alone.
1o Pharmaceutical compositions containing either 6-a,-hydroxy oxymorphone, 6-~i-hydroxy oxymorphone, or mixtures thereof can be used in the invention.
Parenteral administration of 6-hydroxy oxymorphone ensures immediate release into the blood stream and the quickest route to pain relief. Administration of a composition containing 6-hydroxy oxyrnorphone by injection, IV drip, or other means is is most effective. Regardless of the actual route of administration, an amount of 6-hydroxy oxymorphone sufficient to induce analgesia will be supplied. Blood plasma levels of 6-hydroxy oxymorphone must be raised to levels sufficient to induce the desired level of analgesia.
The amount administered will be dependent upon normal criteria such as patient weight, intensity of pain, and other factors. Based on the pharmacokinetic studies blood s plasma levels around at least 0.05 ng/mL will provide some analgesia. The upper plasma level limit will be ultimately established by safety concerns. Over-dosing of any opioid, including 6-hydroxy oxymorphone, can lead to respiratory failure and other undesirable side effects, and can even result in death. Preferably, the blood plasma level of 6 hydroxy oxymorphone will be raised to at least 0.075 ng/mL. Subsequent doses may be io required to maintain these blood levels.
The preferred administration is of 6-hydroxy oxymorphone with appropriate carriers and excipients as will be readily apparent to those skilled in the art. The resulting blood plasma in these preferred administrations will therefore be substantially free of oxymorphone.
is The above description encompasses some preferred embodiments of the invention.
This disclosure is merely illustrative in nature and is not intended to limit the following claims.
s This application relates to provisional patent application serial nos.
60/329,445 filed October 15, 2001, 60/329,432 filed October 15, 2001, 60/303,357 filed July 6, 2001, and 60/329,444 filed October 15, 2001.
1 o Background Field of Invention The invention relates to methods for alleviating pain. More particularly, the invention relates to methods for alleviating pain by administering 6-hydroxy oxymorphone. Most particularly, the invention relates to methods of inducing analgesia ~ s by increasing blood plasma levels of 6-hydroxy oxyrnorphone.
Summary of the Invention The present invention provides methods for treating pain by administration of a pharmaceutical composition comprising 6-hydroxy oxymorphone in an amount sufficient 2o to induce analgesia. In one embodiment, the pharmaceutical composition is administered parenterally, preferably by injection and intravenous drip. To achieve the desired analgesic effect, blood plasma levels of 6-hydroxy oxymorphone are raised to at least approximately 0.05 ng/mL. Methods for administering compositions comprising 6-hydroxy oxymorphone, and one or more carriers, diluents, and excipients in an amount 2s sufficient to induce analgesia are also provided.
Brief Description of the Drawings Fig. 1 is a pharmacokinetic profile for 6-hydroxy oXymorphone with PID scores.
Fig. 2 is a pharmacokinetic profile for oxymorphone with PID scores.
so Fig. 3 is a pharmacokinetic profile for 6-hydroxy oxymorphone with categorical pain scores.
Fig. 4 is a pharmacokinetic profile for oxymorphone with categorical pain scores.
Detailed Description The methods described herein provide for the direct administration of a pharmaceutical composition containing 6-hydroxy oxymorphone as an active ingredient.
s In a preferred embodiment the composition comprising 6-hydroxy oxymorphone alone (excepting, of course, carriers, diluents, and other excipients), In other embodiments, 6-hydorxy oxymorphone may be combined with other opioids or other pharmaceutical agents. For example compositions comprising both 6-hydroxy oxymorphone and its parent, oxymorphone.
io In separate studies, blood plasma levels and indications of pain relief were recorded over a 12 hour period. Figs. 1-4 show graphical representation of the data combining the two studies such that the effect of blood plasma levels on pain can be evaluated.
The administration of oxyrnoiphone yields blood plasma levels of oxymorphone i s and one of its metabolites, 6-hydroxy oxymorphone. Oxymorphone levels peak within 2 hours, fall slightly, and plateau. Interestingly, the level spikes again at 4-6 hours from administration. After this time, oxymorphone levels again drop and eventually fall to levels near the earlier plateau.
Like oxymorphone, 6-hydroxy oxyrnorphone blood plasma levels peak within 2 2o hours after administration. After the initial peak, however, a more or less steady decline in the 6-hydroxy oxymorphone's plasma levels is observed.
Comparing these levels to the pain profiles, a coiTelation between the 6-hydroxy oxyrnorphone blood plasma levels and pain relief can be seen. The pain levels nearly mirror the 6-hydroxy oxyrnorphone levels, with substantial rises in relief near the spikes 2s associated with oxymorphone blood levels. Thus, pain relief can be achieved through administration of 6-hydroxy oxymorphone alone.
In addition to the pharmacol~inetic studies, binding studies have been conducted to compare the binding affinity of 6-hydroxy oxymorphone to that of oxymorphone.
The results are reported in TABLE 1. These results clearly indicate that 6-hydroxy so oxymorphone has great binding affinity for the 8, k and p,, receptor cites, comparable to the binding affinity of its parent. The inventors believe that by virtue of this binding affinity, 6-hydroxy oxymorphone has similar analgesic effects to its parent, oxyrnorphone.
TABLE 1: ASSAY REPORT
s OXYMORPHONE
lOnm lOp,m lOnm lOpm 1.0 1.0 E-5 1.0 E-8 1.0 E-5 Opiate, Delta-4.12% 90.48% -18.26% 89.03%
Opiate, Delta7.19% 55.45% 7.76% 72.74%
2 (Human Recombinant) Opiate, 2.45% 62.47% 10.35% 89.41%
Kappa (Human Recombinant) Opiate, Mu 63.16% 99.91% 85.42% 100.39%
(Human Recombinant) Accordingly, methods of administering the metabolite, 6-hydroxy oxymorphone, directly have been developed. It is believed that the ~ isomer has greater efficacy in the treatment of pain, but this disclosure is not limited to use of that isomer alone.
1o Pharmaceutical compositions containing either 6-a,-hydroxy oxymorphone, 6-~i-hydroxy oxymorphone, or mixtures thereof can be used in the invention.
Parenteral administration of 6-hydroxy oxymorphone ensures immediate release into the blood stream and the quickest route to pain relief. Administration of a composition containing 6-hydroxy oxyrnorphone by injection, IV drip, or other means is is most effective. Regardless of the actual route of administration, an amount of 6-hydroxy oxymorphone sufficient to induce analgesia will be supplied. Blood plasma levels of 6-hydroxy oxymorphone must be raised to levels sufficient to induce the desired level of analgesia.
The amount administered will be dependent upon normal criteria such as patient weight, intensity of pain, and other factors. Based on the pharmacokinetic studies blood s plasma levels around at least 0.05 ng/mL will provide some analgesia. The upper plasma level limit will be ultimately established by safety concerns. Over-dosing of any opioid, including 6-hydroxy oxymorphone, can lead to respiratory failure and other undesirable side effects, and can even result in death. Preferably, the blood plasma level of 6 hydroxy oxymorphone will be raised to at least 0.075 ng/mL. Subsequent doses may be io required to maintain these blood levels.
The preferred administration is of 6-hydroxy oxymorphone with appropriate carriers and excipients as will be readily apparent to those skilled in the art. The resulting blood plasma in these preferred administrations will therefore be substantially free of oxymorphone.
is The above description encompasses some preferred embodiments of the invention.
This disclosure is merely illustrative in nature and is not intended to limit the following claims.
Claims (7)
1. A method of treating pain comprising:
administering parenterally to a patient a pharmaceutical composition comprising 6-hydroxy oxymorphone in an amount sufficient to induce analgesia.
administering parenterally to a patient a pharmaceutical composition comprising 6-hydroxy oxymorphone in an amount sufficient to induce analgesia.
2. The method of claim 1 wherein said pharmaceutical composition is administered by injection or IV drip.
3. The method of claim 1 wherein said administration is sufficient to raise blood plasma levels of 6-hydroxy oxymorphone to at least about 0.05 ng/mL.
4. The method of claim 1 wherein said administration is sufficient to raise blood plasma levels of 6-hydroxy oxymorphone to at least about 0.075 ng/mL.
5. A method of treating pain comprising about parenterally administering to a patient a pharmaceutical composition comprising 6-hydroxy oxymorphone, and one or more carriers, diluents, and excipients in an amount sufficient to induce analgesia.
6. A pharmaceutical comprising 6-hydroxy oxymorphone in a solution for parenteral delivery to animals, including humans.
7. A method of treating pain comprising:
parenterally administering to a patient a pharmaceutical composition comprising 6-hydroxy oxymorphone and oxymorphone in an amount sufficient to induce analgesia.
parenterally administering to a patient a pharmaceutical composition comprising 6-hydroxy oxymorphone and oxymorphone in an amount sufficient to induce analgesia.
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US30335701P | 2001-07-06 | 2001-07-06 | |
US60/303,357 | 2001-07-06 | ||
US32943201P | 2001-10-15 | 2001-10-15 | |
US32944401P | 2001-10-15 | 2001-10-15 | |
US32944501P | 2001-10-15 | 2001-10-15 | |
US60/329,445 | 2001-10-15 | ||
US60/329,444 | 2001-10-15 | ||
US60/329,432 | 2001-10-15 | ||
PCT/US2002/021398 WO2003004031A1 (en) | 2001-07-06 | 2002-07-03 | Parenteral administration of 6-hydroxy-oxymorphone for use as an analgesic |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2452872A1 true CA2452872A1 (en) | 2003-01-16 |
Family
ID=27501826
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002452874A Abandoned CA2452874A1 (en) | 2001-07-06 | 2002-07-03 | Oral administration of 6-hydroxy-oxymorphone for use as an analgesic |
CA002452872A Abandoned CA2452872A1 (en) | 2001-07-06 | 2002-07-03 | Parenteral administration of 6-hydroxy-oxymorphone for use as an analgesic |
CA2452871A Expired - Fee Related CA2452871C (en) | 2001-07-06 | 2002-07-03 | Oxymorphone controlled release formulations |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002452874A Abandoned CA2452874A1 (en) | 2001-07-06 | 2002-07-03 | Oral administration of 6-hydroxy-oxymorphone for use as an analgesic |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2452871A Expired - Fee Related CA2452871C (en) | 2001-07-06 | 2002-07-03 | Oxymorphone controlled release formulations |
Country Status (13)
Country | Link |
---|---|
US (13) | US20030130297A1 (en) |
EP (4) | EP1406630A1 (en) |
JP (4) | JP2005520778A (en) |
KR (1) | KR20030034171A (en) |
CN (3) | CN1268338C (en) |
AT (1) | ATE359077T1 (en) |
AU (3) | AU2002316582B2 (en) |
BR (1) | BR0205721A (en) |
CA (3) | CA2452874A1 (en) |
DE (1) | DE60219478T2 (en) |
ES (1) | ES2284888T3 (en) |
NO (1) | NO20031018L (en) |
WO (3) | WO2003004031A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US9820982B2 (en) | 2001-07-06 | 2017-11-21 | Endo Pharmaceuticals Inc. | Oxymorphone controlled release formulations |
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US5478577A (en) * | 1993-11-23 | 1995-12-26 | Euroceltique, S.A. | Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level |
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UA81224C2 (en) | 2001-05-02 | 2007-12-25 | Euro Celtic S A | Dosage form of oxycodone and use thereof |
US8329216B2 (en) | 2001-07-06 | 2012-12-11 | Endo Pharmaceuticals Inc. | Oxymorphone controlled release formulations |
PL207748B1 (en) * | 2001-07-06 | 2011-01-31 | Penwest Pharmaceuticals Company | Sustained release formulations of oxymorphone |
US20030091635A1 (en) * | 2001-09-26 | 2003-05-15 | Baichwal Anand R. | Opioid formulations having reduced potential for abuse |
US7776314B2 (en) | 2002-06-17 | 2010-08-17 | Grunenthal Gmbh | Abuse-proofed dosage system |
HUE038446T2 (en) | 2002-09-20 | 2018-10-29 | Alpharma Pharmaceuticals Llc | Sequestering subunit and related compositions and methods |
US20070048228A1 (en) | 2003-08-06 | 2007-03-01 | Elisabeth Arkenau-Maric | Abuse-proofed dosage form |
DE10361596A1 (en) | 2003-12-24 | 2005-09-29 | Grünenthal GmbH | Process for producing an anti-abuse dosage form |
DE102005005446A1 (en) | 2005-02-04 | 2006-08-10 | Grünenthal GmbH | Break-resistant dosage forms with sustained release |
DE10336400A1 (en) | 2003-08-06 | 2005-03-24 | Grünenthal GmbH | Anti-abuse dosage form |
CN1934141A (en) * | 2004-03-22 | 2007-03-21 | 纳幕尔杜邦公司 | Orthoester-protected polyols for low VOC coatings |
DE102004032049A1 (en) | 2004-07-01 | 2006-01-19 | Grünenthal GmbH | Anti-abuse, oral dosage form |
DE102005005449A1 (en) | 2005-02-04 | 2006-08-10 | Grünenthal GmbH | Process for producing an anti-abuse dosage form |
US8394812B2 (en) | 2005-08-24 | 2013-03-12 | Penwest Pharmaceuticals Co. | Sustained release formulations of nalbuphine |
US8497258B2 (en) | 2005-11-12 | 2013-07-30 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
US20070212414A1 (en) * | 2006-03-08 | 2007-09-13 | Penwest Pharmaceuticals Co. | Ethanol-resistant sustained release formulations |
US20080119501A1 (en) * | 2006-04-28 | 2008-05-22 | Hein William A | Immediate release oxymorphone compositions and methods of using same |
EP2484346B1 (en) | 2006-06-19 | 2017-02-22 | Alpharma Pharmaceuticals LLC | Pharmaceutical compositions |
CA2652980A1 (en) * | 2006-10-10 | 2008-04-17 | Penwest Pharmaceuticals Co. | Robust sustained release formulations of oxymorphone |
CN101578094A (en) * | 2006-10-10 | 2009-11-11 | 潘威斯脱药物公司 | Robust sustained release formulations of oxymorphone and methods of use thereof |
US20080085305A1 (en) * | 2006-10-10 | 2008-04-10 | Penwest Pharmaceuticals Co. | Robust sustained release formulations of oxymorphone |
US20080085303A1 (en) * | 2006-10-10 | 2008-04-10 | Penwest Pharmaceuticals Co. | Robust sustained release formulations of oxymorphone and methods of use thereof |
MX2009003771A (en) * | 2006-10-10 | 2009-07-22 | Penwest Pharmaceuticals Co | Robust sustained release formulations. |
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Publication number | Priority date | Publication date | Assignee | Title |
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US9820982B2 (en) | 2001-07-06 | 2017-11-21 | Endo Pharmaceuticals Inc. | Oxymorphone controlled release formulations |
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