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Morphine and Morphine Precursors

a technology of morphine and precursors, applied in the field of morphine and morphine precursors, can solve the problems of few successful treatments available for these people, and achieve the effect of reducing the risk of overdosing

Inactive Publication Date: 2008-09-11
THE RES FOUND OF STATE UNIV OF NEW YORK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes methods and compositions for using morphine and related compounds to treat various conditions in mammals. These methods involve repeatedly administering low doses of morphine or its precursors to induce nitric oxide release and reduce inflammation, pain, and behavioral changes. The methods can be used to treat neural, immune, vascular, gastrointestinal, and addiction conditions. The compositions can contain morphine or its precursors, as well as other ingredients such as selenium, arginine, calcium, or thebaine. The methods and compositions can help to reduce the risk of overdosing and provide a safer alternative to opioid addiction.

Problems solved by technology

In many cases, few, if any, successful treatments are available for these people.
In addition, the use of low doses of morphine can allow patients to experience the beneficial effects of morphine, while not experiencing possible negative effects of morphine (e.g., addiction or powerful analgesia).

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Reticuline Exposure to Invertebrate Ganglia Increases Endogenous Morphine Levels

[0100]The following experiments were performed to determine if exposing tissues to an opiate alkaloid precursor, reticuline, would result in increasing endogenous morphine levels.

Material and Methods

[0101]Mytilus edulis collected from the local waters of Long Island Sound were maintained under laboratory conditions for at least 14 days prior using in experiments. Mussels were kept in artificial seawater (Instant Ocean, Aquarium Systems, Mentor, Ohio) at a salinity of 30 PSU and at a temperature of 18° C. as previously described (Stefano et al., Electro-Magnetobiol., 13:123-36 (1994)).

[0102]For reticuline exposure, 400 animals were placed and maintained in artificial seawater at 24° C., whereas control animals (100) were exposed to vehicle (PBS). For the biochemical analysis, groups of 20 animals had their pedal ganglia excised at different time periods after incubation with reticuline.

[0103]The extractio...

example 2

Mammalian Cells Produce Morphine from Reticuline

[0118]Human cells (NCI-H295R) were adapted from the NCI-H295 pluripotent adrenocortical carcinoma cell line (ATCC CRL-10296), which is from a carcinoma of the adrenal cortex. The original cells were adapted to a culture medium that decreased the population doubling time from 5 days to 2 days. While the original cells grew in suspension, the adapted cells were selected to grow in a monolayer. These cells retained the ability to produce adrenal androgens and were responsive to angiotensin II and potassium ions. To propagate these cells, the culture medium was a 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F12 medium containing 15 mM HEPES, 0.00625 mg / mL insulin, 0.00625 mg / mL transferrin, 6.25 ng / mL selenium, 1.25 mg / mL bovine serum albumin, and 0.00535 mg / mL linoleic acid, 97.5%; Nu-Serum I, 2.5%. See, e.g., Rainey et al., Mol. Cell. Endocrinol., 100:45-50 (1994); Gazdar et al., Cancer Res., 50:5488-5496 (1990); and Bird ...

example 3

The Combination of L-DOPA and Dopamine Inhibits Endogenous Morphine Production

[0121]Mytilus pedal ganglia were obtained and incubated with 10 μg L-DOPA alone, 10 μg dopamine alone, or 10 μg L-DOPA plus 10 μg dopamine. The control ganglia were not incubated with L-DOPA or dopamine and exhibited 11.9 ng / mL morphine. The ganglia incubated with either L-DOPA alone or dopamine alone exhibited 9.31 and 8.82 ng / mL morphine, respectively. In contrast, ganglia incubated with both L-DOPA and dopamine exhibited 5.52 ng / mL of morphine. These results demonstrate that treatment with both L-DOPA and dopamine can reduce morphine production.

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Abstract

Methods and materials related to the use of morphine, morphine precursors (e.g., reticuline), and inhibitors of morphine synthesis or activity to treat diseases, to reduce inflammation, or to restore normal function are provided.

Description

[0001]Statement as to Federally Sponsored Research Funding for the work described herein was provided by the federal government, which may have certain rights in the invention.BACKGROUND[0002]1. Technical Field[0003]This document relates to methods and materials involved in using morphine, morphine precursors (e.g., reticuline), morphine-6β-glucuronide, and inhibitors of morphine synthesis or activity to treat mammals.[0004]2. Background Information[0005]Many people suffer from conditions such as depression, neurodegenerative diseases (e.g., Alzheimer's disease), pro-inflammatory diseases, autoimmune disorders, and atherosclerosis. In many cases, few, if any, successful treatments are available for these people.[0006]Morphine is a powerful analgesic that is routinely used to reduce pain in humans. For example, surgery patients are typically instructed to take 5 to 10 mg of morphine per person to alleviate pain caused by the surgical procedure. In some cases, patients suffering from ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/485A61P25/00
CPCA23L1/30A61K31/472A61K31/198A61K31/485A61K31/7052A61K33/04A61K33/06A23V2002/00A61K31/194A61K45/06A61K2300/00A23V2200/322A23V2250/30A23V2250/0606A23V2250/1626A23L33/10A61P9/10A61P17/00A61P19/02A61P25/00A61P25/16A61P25/18A61P25/22A61P25/24A61P25/28A61P25/30A61P29/00A61P43/00
Inventor STEFANO, GEORGE B.CADET, PATRICKMANTIONE, KIRK J.ZHU, WEI
Owner THE RES FOUND OF STATE UNIV OF NEW YORK
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