Papaver somniferum strain with high concentration of thebaine
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Publication Number
US-10760090-B2
Publication Date
2020-09-01
Expiration Date
Abstract
The present invention is directed to an improved poppy straw, concentrate of poppy straw and opium of Papaver somniferum for the production of thebaine containing little or no oripavine, codeine or morphine. The present invention also provides plants, stands and seeds of Papaver somniferum and methods for the production of thebaine.
Core Innovation
The invention describes a stably reproducing Papaver somniferum plant and mutagen-derived lines that yield poppy straw having a thebaine-dominant alkaloid combination with low oripavine, and little or no morphine or codeine. Thebaine constitutes about 95% by weight or greater of the alkaloid combination, oripavine about 5% by weight or less, and thebaine constitutes about 3.0% or greater of the poppy straw on a dry weight basis. The document addresses the cost and limitation of thebaine production from morphine-dominant capsules and the persistence of oripavine in prior approaches.
Greenhouse-to-field evaluation of mutagen-derived Papaver somniferum lines across M2–M5 generations identifies plants with stable thebaine-dominant compositions and low oripavine using UPLC and HPLC analysis. Early genetics evidence indicates segregation into four chemotypes, including thebaine-only and other chemotypes, suggesting two genes contributing to thebaine-only trait, supported by chi-square tests versus a 9:3:3:1 expectation. The persistence of low oripavine content is confirmed in later generations through green-capsule latex testing and harvested straw analysis.
The genetic and enzymatic rationale is described in terms of inhibiting conversion of thebaine to oripavine, including mention of phenolic O-demethylase and involvement of a TOP1-related pathway disruption. Mutagenized poppy seeds are grown to plants bearing a leaf or an immature poppy capsule, alkaloids are sampled for presence of thebaine, oripavine, morphine and codeine, and the process is repeated and optionally continued through self-fertilized generations until a stably heritable high thebaine content and low oripavine content is obtained.
Claims Coverage
The independent claims cover three inventive features: a stably reproducing Papaver somniferum plant, a mutagenizing-and-selecting method to obtain a mutant poppy plant, and an alkaloid combination with specified thebaine and oripavine bounds.
Stably reproducing high-thebaine, low-oripavine Papaver somniferum plant
A stably reproducing Papaver somniferum plant which yields poppy straw having a thebaine fraction of about 95% by weight or greater and an oripavine fraction of about 5% by weight or less of an alkaloid combination comprising morphine, codeine, thebaine and oripavine, wherein thebaine constitutes about 3.0% or greater of the poppy straw on a dry weight basis, and the plant is stably reproducing by self pollination in respect of the thebaine and oripavine fractions and the thebaine content of the poppy straw.
Mutagenizing seeds to obtain stably heritable high thebaine and low oripavine
A method comprising exposing at least one Papaver somniferum poppy seed to a mutagenizing agent to produce at least one mutagenized poppy seed; growing the mutagenized seed to produce a plant bearing a leaf or an immature poppy capsule, optionally through multiple self-fertilized generations; sampling the leaf or poppy capsule for presence of thebaine, oripavine, morphine and codeine; and repeating the steps until a poppy plant is obtained which yields poppy straw having thebaine constituting about 95% by weight or greater and oripavine constituting about 5% by weight or less of the alkaloid combination, and wherein thebaine constitutes about 3.0% or greater of the alkaloid content of the poppy straw on a dry weight basis.
Alkaloid combination dominated by thebaine with limited oripavine
An alkaloid combination wherein thebaine constitutes about 90% by weight or greater and oripavine constitutes about 10% by weight or less, wherein the alkaloid combination comprises morphine, codeine, thebaine and oripavine.
Together, the independent claims define Papaver somniferum plants that reproducibly yield poppy straw with high-thebaine and low-oripavine alkaloid fractions, a mutagenizing-and-selecting method to obtain stably heritable plants meeting those thresholds, and an alkaloid combination with thebaine and oripavine constrained by specified weight-percentage bounds.
Stated Advantages
Produces thebaine with minimal oripavine and little or no morphine or codeine.
Targets thebaine-dominant alkaloid combinations with low oripavine.
Documented Applications
Poppy straw produced by harvesting poppy capsules from the stably reproducing Papaver somniferum plant.
A method for producing a mutant poppy plant of Papaver somniferum yielding stably high thebaine content and low oripavine content.
An alkaloid combination comprising morphine, codeine, thebaine and oripavine.
A seed produced by a poppy plant containing the alkaloid combination.
Opium and a concentrate of poppy straw derived from the plant, where applicable by the dependent claim scope.
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