Elan Pharmaceuticals, Inc.

Neurex Corporation

Leland Stanford Junior University

Siteone Therapeutics, Inc.

Jazz Pharmaceuticals International Limited

Azur Pharma International Limited

Tersera Therapeutics LLC

George P Miljanich

David J Ellis

David E Shields

Karen L Valentino

Stephen S Bowersox

Alan Justice

Kishor Chandra Gohil

Tejinder Singh

Justin Du Bois

James A Fox

Robert S Bitner

John Mulcahy

Hassan Pajouhesh

Donald H Yamashiro

Grant Masaaki Shibuya

Anton Delwig

Laszlo Nadasdi

Jacob Beckley

Balazs G Szoke

Laszlo Urge

Robert W Newcomb

Katalin Tarczy-Hornoch

Andrew L Palma

Robin Dean

Ruth L Cong

Makoto Tsubokawa

William F Hopkins

James Ross Walker

Jeffrey E Merit

James L Miller

Matthew Axtman

David Shields

Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R, R, R, R, and Xare as described herein.

11,13-modified saxitoxins for the treatment of pain

Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R, X, and Xare as described herein. 

Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R, R, R, R, and Xare as described herein. 

The present invention is directed to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl l, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the &#x3c9;-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, an antioxidant, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

Method for administering omega-conopeptide

The present invention is directed to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl 1, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the &#x3c9;-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, an antioxidant, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R, Xand Xare as described herein.

Provided herein are compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function, for example conditions associated with pain. The compounds are 10',11&#x2032;-modified saxitoxins. The compounds are optionally additionally modified at carbon 13. In certain embodiments, the 10&#x2032;,11&#x2032;-modified saxitoxins are of Formula I: where R, Rand Rare as described herein. Also provided herein are methods of treating pain in a mammal comprising administering an effective treatment amount of a 10&#x2032;,11&#x2032; modified saxitoxin or composition to a mammal. In an embodiment, the mammal is a human. 

10',11&#x2032;-modified saxitoxins useful for the treatment of pain

Method for administering &#x3c9;-conopeptide

The present invention is directed to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the &#x3c9;-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, an antioxidant, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

Pharmaceutical formulation for reducing pain

The present invention is direct to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyil, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the &#x3c9;-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, an antioxidant, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

Method for reducing pain

Method for reducing pain with ziconotide and morphine

Method for reducing pain with ziconotide and baclofen

Pharmaceutical formulations for reducing pain

Growing community of inventors

Redwood City, CA, United States of America

George P Miljanich