38 results about "Thebaine" patented technology

The invention provides a method for synthesizing naloxone or naltrexone, which comprises the following steps of: dissolving thebaine in formic acid, uniformly stirring, dripping an oxidant, keeping the temperature of between 20 and 40 DEG C for 3 to 7 hours, displacing gas in a reaction vessel by inert gas serving as protective gas for 3 to 5 times, adding a metallic framework catalyst, displacing the gas by hydrogen for 3 to 5 times, keeping the temperature of between 25 and 45 DEG C and stabilizing a system for 7 to 13 hours to obtain a compound 2; reacting the compound 2 with acetic anhydride at the temperature of between 60 and 100 DEG C for 1 to 2 hours to obtain a compound 3; taking the inert gas as the protective gas, adding toluene, chloroformic acid-1-chloroethyl ester and potassium bicarbonate into the compound 3, heating to the temperature of between 75 and 100 DEG C and reacting for 20 to 40 hours, concentrating under reduced pressure until the system is fully dry, adding 10 percent hydrochloric acid, and heating and refluxing for 2 to 6 hours to obtain a compound 4; dissolving the compound 4 and at least one alkylation reagent in an organic solvent 1 and reacting with alkali at the temperature of between 50 and 100 DEG C to obtain a compound 5; and reacting the compound 5 with boron tribromide in an organic solvent 2 at the temperature of between -10 and 40 DEG C for 2 to 4 hours to obtain a compound 6, namely the naloxone or naltrexone.

The present invention provides methods for the conversion of thebaine to a morphine derivative, such as hydrocodone. Novel ketal intermediates of the conversion are provided. A one-pot procedure for the conversion comprises treating thebaine with an acid in the presence of a metal catalyst.

Thebaine is manufactured in high yields and with a high purity using codeine or a salt of codeine as the starting material. The manufacturing process involves the following steps:(a) codeine or a codeine salt (e.g., codeine phosphate) is converted into the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine;(b) the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine resulting from step (a) is oxidized to yield the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine;(c) the intermediate N-carboalkoxy- or N-carboaryloxynorcodeinone resulting from step (b) is enolized with a base and the resultant enolate is thereafter methylated to yield the intermediate N-carboalkoxy- or N-carboaryloxynorthebaine; and(d) the intermediate N-carboalkoxy- or N-carboaryloxynorthebaine resulting from step (c) is reduced to yield thebaine.

The invention discloses a method for constructing standard fingerprints by applying terahertz waves to detect stupefacient, which comprises the following steps: preparing a standard sample of the stupefacient which is any one of morphine, thebaine, papaverine hydrochloride, cocaine hydrochloride and pethidine hydrochloride, and detecting the standard sample of the stupefacient and constructing a standard fingerprint database by applying a terahertz spectroscopic device; and detecting an unknown sample by using the constructed standard fingerprint database. The terahertz technology can accurately judge sorts of drugs in packaging materials. Detections to the drugs with terahertz do not damage human bodies, materials and drugs, thereby realizing nondestructive detection.

The invention discloses a method for detecting an anesthetic medicament by a standard fingerprint map established by applying terahertz waves, which comprises the following steps: preparing a standard sample of the anesthetic medicament, wherein the anesthetic medicament is any one of morphine, thebaine, papaverine hydrochloride, cocaine hydrochloride, and meperidine hydrochloride; detecting the standard sample of the anesthetic medicament by applying a terahertz spectrum device and establishing a standard fingerprint map library; and detecting an unknown sample by using the established standard fingerprint map library. The kind of drugs in packing materials can be accurately judged through the terahertz technology. The terahertz is used for detecting the drugs without damaging human bodies, materials and drugs. Therefore, non-destructive testing can be realized.

The invention discloses a method for treating opium poppy extract, which comprises the following steps: a, adding a polar solvent into the opium poppy extract, and reacting to obtain a first treating fluid; b, adding a filter aid into the first treating fluid, and filtering to obtain a first extract liquid; c, separating the first extract liquid through a chromatographic column which is filled with spherical silica gel of a bonded stationary phase and a mixture of alcohol and inorganic acid serving as a mobile phase; and d, eluting to obtain a fraction containing alkaloid. Compared with the prior art, the method has the advantages of separating morphine, codeine, thebaine and other monomer alkaloids, and the alkaloid monomer has high purity and large yield.

The invention discloses a method for rapidly determining morphine, codeine, thebaine, papaverine and narcotine in hot-pot food and belongs to the field of food safety. The method includes extracting the morphine, the codeine, the thebaine, the papaverine and the narcotine in the hot-pot food by water-acetonitrile (V-V, 1:1), removing oil and fat (food containing oil and fat) by normal hexane, qualitatively and quantitatively analyzing by DART-MS / MS (direct analysis in real time ion source-mass spectrum / mass spectrum), and performing quantitative calculation and methodology validation according to an internal standard method. Conditions of a mass spectrometer include that an ionization mode is a positive ion mode, the DART ion source temperature is 350 DEG C, grid-electrode voltage is 350V, voltage of a mass spectrum-mass analyzer is 4,000V, ion strength of parent ions / quantitative ions / qualitative ions is that the morphine 286 / 181 / 165, the morphine -D3 289 / 165 / 152, the codeine 300-215-165, the codeine -D303 / 215 / 165, the thebaine 312 / 58 / 249, the papaverine 340 / 202 / 171 and the narcotine 414 / 220 / 353 (wherein the thebaine, the papaverine and the narcotine take the codeine -D3 as an internal standard), and secondary scanning serves as a scanning mode.

The invention discloses a method for rapidly identifying illegally added poppy shells in herbal tea. The method comprises the following steps: (1) carrying out ultrasonic treatment on a liquid herbal tea sample to obtain a herbal tea sample, regulating the herbal tea sample to be slightly alkaline, adding an organic solvent and sodium chloride, carrying out vortex extraction, centrifuging, layering, adding an ammonium acetate solution into supernatant, and uniformly mixing, thereby obtaining to-be-tested liquid; or adding an organic solvent into a solid herbal tea sample, carrying out ultrasonic treatment, cooling an extracting solution to room temperature, making up to constant volume, adding an ammonium acetate solution into the extracting solution, and uniformly mixing, thereby obtaining to-be-tested liquid; and (2) filtering the to-be-tested liquid by virtue of an organic phase filter membrane, with an acetic acid-methanol solution and an ammonium acetate solution as a mobile phase, carrying out reversed phase chromatographic column separation, and detecting five main ingredients, namely morphine, codeine, thebaine, papaverine and narcotine, in the poppy shells on eluent by adopting an ultra-high performance liquid chromatography-tandom mass spectrometer. The method disclosed by the invention has the advantages that pretreatment is simple and rapid, qualitative and quantitative treatment is accurate, and the illegally added poppy shell ingredients in the herbal tea can be rapidly and reliably detected.

Plant material enriched in secondary metabolites is produced in tissue culture under conditions that organogenically produce a proliferation of shoots and leafy material, and harvesting the leafy material and shoots while in a green, actively-growing, non-senescent stage. Of particular interest is plant material that produces alkaloids, especially material from poppy (Papaver sp.) that will yield economically attractive levels of morphinane alkaloids, particularly thebaine.

The invention relates to combined application of a CNS (central nerves system) inhibitor and opioids in endoscopy, in particular to application of the CNS inhibitor and the opioids in preparation of drugs for calming and / or anesthesia in gastroscopy. The CNS inhibitor is remimazolam or pharmaceutical salts thereof, and the opioids are selected from morphine, codeine, thebaine, sufentanil, carfentanil, fentanyl, lofentanil, alfentanil, ohmefentanyl, remifentanil and the like.

The invention belongs to the field of pharmacy, and relates to a fused ring morphines derivative, and a preparation method therefor and application thereof. The invention particularly relates to 7 alpha-(4'-substituted amino-phenyl)-6 alpha, 14 alpha-endo-ethylidene (alkenyl)-tetrahydrothebaine series derivatives of a general formula (I) and pharmaceutically acceptable salts. The derivatives of the general formula (I) are prepared by reaction of thebaine and substituted styrenes reagents and a series of conversion, and 7 alpha-(4'-benzamido-phenyl)-6 alpha, 14 alpha-endo-ethylidene (alkenyl)-tetrahydrothebaine is a typical high-selectivity k ligand, and can be used for preparing drugs for stopping pain, resisting depression, resisting opiate addiction, relieving itching and the like. The formula is as shown in the specification.

The invention belongs to the pharmaceutical field, and relates to a derivative of 7-Alpha-substituted phenyl-tetrahydrothebaine shown in formula (I) and the pharmaceutically-accepted salts thereof. The derivative shown in formula (I) is prepared by the following steps: reacting with substituted styrene reagent via thebaine, and then subjecting to the related conversion. According to the results of the animal experiment, the compound has analgesic activity, wherein 7-Alpha-(4'-amino-phenyl)-6-Alpha, 14-Alpha-endo-vinylidene-tetrahydrothebaine hydrochloride (LQ004C) has an activity to the isolated tissue, which is similar to butophanol tartrate, and is a typical Kappa excitant; and the compound exhibits remarkable analgesic activity in the mice acetic acid writhing method and the mice heat radiation tail-flick method, and can be further prepared into low-addiction analgetics.

The invention belongs to the pharmaceutical field and relates to 8alpha substituted aryl-4, 5-epoxy morphinan derivatives shown in formula (I) or salts thereof, a preparation method and the usage of the compound in treating pains. The compound is prepared by Thebaine or analogs thereof reacting with agents containing single substituted ethylenes and by a corresponding transformation method. Test results of in vitro experiments show that the representative compound of the invention shows combining ability and activation ability on mu opioid receptors corresponding to morphine and has high selectivity for the mu opioid receptors but basically has no affinity to other opioid receptor subtypes. The compound of the invention belongs to mu excitant with new structure type and high selectivity and can be further made into pain relievers with strong pain relieving function and low endurance and addiction.

The invention relates to the field of the double bond hydrogenation reaction of a thenorphine intermediate, in particular to a preparation method of 7alpha-acetyl-6,14-ethyl bridge tetrahydrothebaine. The method comprises the following steps of: dissolving 7alpha-acetyl-6,14-ethylene bridge tetrahydrothebaine serving as a raw material into a polar solvent; adding an effective quantity of catalyst and organic alkaline reagent; and introducing an excessive amount of hydrogen at certain temperature and under certain pressure for undergoing a hydrogenation reduction reaction to obtain 7alpha-acetyl-6,14-ethyl bridge tetrahydrothebaine, wherein the polar solvent is absolute ethyl alcohol or absolute methanol; the catalyst is palladium carbon or platinum dioxide; the organic alkaline reagent is pyridine; and the using amount of the organic alkaline reagent is 1-5 percent (v / w) based on the amount of the 7alpha-acetyl-6,14-ethylene bridge tetrahydrothebaine. The method disclosed by the invention has the advantages of high operating safety, high product yield and low production cost.

The invention belongs to the field of chemical pharmacy and relates to a 7beta-methyl-tetralone derivative shown in a general formula (I) and a preparation method thereof. According to the compound shown in the general formula (I), with thebaine as a raw material, through related conversion methods such as N-demethylation, N-acylation, a Diels-Alder reaction and reduction, oxidation and Grignard reactions, the compound is synthesized. The compound shown in the general formula (I) belongs to an opioid receptor ligand, a radioactive receptor ligand combination experiment is adopted, the affinityand selectivity of the ligand to three subtypes of an opioid receptor are measured, and a [35S]GTPgammaS combination experiment is adopted for measuring the excitement inhibitory activity of the ligand; it is proved through a result that the compound has the functions of alleviating pain, resisting depression, withdrawing opioid addiction, relieving itching and the like and can be applied to preparation of an opioid receptor treatment medicine and applied to clinical analgesia or depression resistance or opioid addiction withdrawal treatment or itching relieving treatment.

The invention relates to a preparation method of a compound with a general formula (I) or pharmaceutically acceptable salts thereof, and relates to an application of the derivatives in the field of opioid receptor treatment, and an application of the derivatives in preparation of medicines for treating pain, depression, opioid addiction and pruritus. The treatment of pains comprise treatment or relief of pains, chronic pains, neuropathic pains and cancer pains during an operation; the pruritus comprises intractable pruritus accompanied by serious diseases such as uremia, diabetic nephropathy, chronic liver diseases and malignant tumors. Formula (I) as shown in the specification,.

The invention relates to the technical field of medicine synthesis, and discloses a thebaine derivative and a preparation method thereof. The invention also discloses an application of the thebaine derivative in preparation of codeine, the codeine can be prepared from the thebaine derivative only through several simple steps of conversion, and the prepared codeine can be further converted into morphine in one step, wherein in the reaction process, the used reagents are common chemical reagents and do not need to be specially prepared; meanwhile, the requirements on conditions of each reaction are not harsh, the sensitivity to substances such as water and oxygen is not high, the post-treatment of each reaction step is simple, the operability is great, and the effects of high reaction yield and simple operation are achieved.

The invention belongs to the technical field of medicament synthesis, and relates to a synthetic method of naloxone hydrochloride. The method comprises the following steps: by adopting thebaine as a starting material, oxidizing and then reducing thebaine to obtain a compound 2, reacting the compound 2 with acetic anhydride to obtain an ester compound 3, then removing methyl and performing hydrolysis to obtain a compound 4, reacting the compound 4 with an alkylating reagent (such as the reagent selected from chloropropene, bromopropene, iodopropylene or the combination thereof), performing allylation on the Nth bit of a mother nucleus structure to obtain a compound 5, then removing methyl to obtain naloxone free alkali, then forming acid addition salts with hydrochloric acid, and then refining to obtain naloxone hydrochloride which can be used as a medicinal raw material medicament. By adopting the method disclosed by the invention, a high-quality medicinal raw material medicament can be prepared.

The invention relates to a quick detecting method for papaverine, narcotine and thebaine. The quick detecting method comprises the steps of sample selection, pretreatment and determination, wherein the pretreatment comprises the following steps: adding pure water, acetonitrile and anhydrous sodium acetate into a sample, carrying out swirl oscillations, then adding anhydrous magnesium sulfate for swirl oscillations, and then centrifuging, taking a supernatant fluid for rotary evaporation till being dried, using a solving liquid for solving, and passing through a film and waiting for detecting.According to the quick detecting method provided by the invention, on the basis of QuEChERS principle adopting the matrix dispersing theory, the quick, accurate, economical and convenient detecting method for simultaneously detecting contents of various alkaloids such as pericarpium papaveris components in foods is established. The detection limit, the recovery percent, and the precision of the method all meet detecting requirements. The detecting method established can be used for detecting papaverine, narcotine and thebaine in soy sauce stewed foods and seasoning packets and soup sticks therefor, and also can be used for detecting papaverine, narcotine and thebaine in hotpot seasonings, sauce packets, seasoning powders and various soup-stock materials.

The invention relates to a tridemorph synthesis process which includes the steps: adding tridecyl alcohol and optional solvents into a reaction kettle, adding a catalyst, stirring and mixing mixture,leading into hydrogen, and heating the reaction kettle; adding 2, 6-thebaine when the temperature of the reaction kettle reaches the temperature of 200 DEG C or more, and maintaining the reaction kettle to perform reaction in a certain pressure and at a certain temperature until reaction is completed; post-processing a reactant to obtain a reactant finished product. According to the tridemorph synthesis process, the tridemorph with the purity larger than 99% is acquired under the conditions of high selectivity and high yield, and waste water, waste gas and industrial residues are greatly reduced.

The invention relates to a method for extracting and separating thebaine from pericarpium papaveris, which comprises the following steps: (1) extracting or leaching pericarpium papaveris, of which thethebaine content is greater than 1% by using 0.5% acetic acid solution by a leakage method to obtain an extracting solution; (2) adsorbing and enriching the extracting solution by using macroporous resin or anion resin, and performing elution and desorption to obtain a desorption solution; (3) concentrating the desorption solution to be thick, adding a sodium hydroxide solution with the volume concentration of more than 20%, carrying out alkaline boiling, cooling the mixture to room temperature, and filtering the mixture to obtain a thebaine solid; (4) dissolving the thebaine solid in an acidsolution, adjusting the pH value with a 30% sodium hydroxide solution, crystallizing, filtering, and drying the filter cake to constant weight to obtain crude thebaine; and (5) crystallizing the crude thebaine with 95% ethanol to obtain a thebaine alkali product. The method is small in investment, high in yield and safe.

The invention belongs to the technical field of medicament synthesis, and relates to a synthetic method of naloxone hydrochloride. The method comprises the following steps: by adopting thebaine as a starting material, oxidizing and then reducing thebaine to obtain a compound 2, reacting the compound 2 with acetic anhydride to obtain an ester compound 3, then removing methyl and performing hydrolysis to obtain a compound 4, reacting the compound 4 with an alkylating reagent (such as the reagent selected from chloropropene, bromopropene, iodopropylene or the combination thereof), performing allylation on the Nth bit of a mother nucleus structure to obtain a compound 5, then removing methyl to obtain naloxone free alkali, then forming acid addition salts with hydrochloric acid, and then refining to obtain naloxone hydrochloride which can be used as a medicinal raw material medicament. By adopting the method disclosed by the invention, a high-quality medicinal raw material medicament can be prepared.

The present invention relates to poppy cultivars and their use to produce thebaine. In specific forms, the present invention relates to cultivars of Papaver bracteatum that produce thebaine in the first growing season after germination.

The invention belongs to the field of pharmacy, and relates to condensed ring morphine derivatives, a preparation method and application thereof. It specifically relates to 7α-(4'-substituted amino-phenyl)-6α, 14α-endo-ethenide (en)yl-tetrahydrothebaine series derivatives of general formula (I) and pharmaceutically acceptable salts ; The derivative of the general formula (I) is prepared by reacting thebaine with a substituted styrene reagent and through a series of conversion methods, wherein 7α-(4'-benzamido-phenyl)-6α, 14α-endo ‑Ethylidene‑tetrahydrothebaine is a typical highly selective κ ligand, which can be used to prepare drugs such as analgesia, antidepression, opioid addiction, and antipruritic.