36 results about "Rimantadine" patented technology

The invention provides compositions and methods for treating autoimmune diseases such as multiple sclerosis. The compositions include a combination of an NMDA Receptor antagonist, such as memantine or rimantadine, and a fumarate agent, such as dimethyl fumarate.

Disclosed are conjugates in which an aminoadamantane derivative, such as amantadine, memantine, or rimantadine is linked to a therapeutic agent. The conjugate can then be used to target the therapeutic agent to an injured neuron.

Compositions for pharmaceutical and other uses comprising clear aqueous solutions of bile acids which do not form any detectable precipitates over selected ranges of pH values of the aqueous solution and methods of making such solutions. The compositions of the invention comprise water; a bile acid in the form of a bile acid, bile acid salt, or a bile acid conjugated with an amine by an amide linkage; and either or both an aqueous soluble starch conversion product and an aqueous soluble non-starch polysaccharide. The composition remains in solution without forming a precipitate over a range of pH values and, according to one embodiment, remains in solution for all pH values obtainable in an aqueous system. The composition, according to some embodiments, may further contain a pharmaceutical compound in a pharmaceutically effective amount. Non-limiting examples of pharmaceutical compounds include insulin, heparin, bismuth compounds, amantadine and rimantadine.

The present invention relates to targets for Human microRNAs in Avian Influenza Virus (H5N1) Genome and provides specific miRNA targets against H5N1 virus. Existing therapies for Avian flu are of limited use primarily due to genetic re-assortment of the viral genome, generating novel proteins, and thus escaping immune response. In animal models, baculovirus-derived recombinant H5 vaccines were immunogenic and protective, but results in humans were disappointing even when using high doses. Currently, two classes of drugs are available with antiviral activity against influenza viruses: inhibitors of the M2 ion channel, amantadine and rimantadine, and inhibitors of neuraminidase, oseltamivir, and zanamivir. There is paucity of information regarding effectiveness of these drugs in H5N1 infection. These drugs are also well known to have side effects like neurotoxicity. Thus there exists a need to develop alternate therapy for targeting the Avian flu virus (H5N1). The present invention addresses this need in the field.

Antimicrobial compositions containing two or more antiviral agents coupled to a polymer and methods of making and using the compositions, are described herein. In one embodiment, two or more antiviral agents are covalently coupled to the polymer. Suitable antiviral agents include, but are not limited to, sialic acid, zanamivir, oseltamivir, amantadine, rimantadine, and combinations thereof. The polymer is preferably a water-soluble, biocompatible polymer. Suitable polymers include, but are not limited to, poly(isobutylene-alt-maleic anhydride) (PIBMA), poly(aspartic acid), poly(l-glutamic acid), polylysine, poly(acrylic acid), plyaginic acid, chitosan, carboxymethyl cellulose, carboxymethyl dextran, polyethyleneimine, and blends and copolymers thereof. In another embodiment, the compositions contain a physical mixture of polymer containing one antiviral agent and polymer containing a second antiviral agent. The compositions can be formulated for enteral or parenteral administration. Suitable oral / intranasal dosage forms include, but are not limited to, tablets, capsules, solutions, suspensions, emulsions, syrups, and lozenges. Suitable dosage forms for parenteral administration include, but are not limited to, solutions, suspensions, and emulsions. The compositions described herein are effective at treating a variety of infections, including viral infections such as influenza, while inhibiting or preventing the development of microbial resistance.

The invention belongs to the technical field of poultry product detection and relates to a combined detection method of amantadine, rimantadine, ribavirin and moroxydine residues in eggs. The method comprises the following steps: carrying out low temperature repetitive freeze-thawing on a sample, adding a formic acid-methanol solution, mixing, centrifuging, taking a supernatant for standby, adding water saturated n-hexane, mixing, carrying out ultrasonic treatment, centrifuging to remove n-hexane floccules on the upper layer with an extracting solution left at the lower layer, purifying with a cation exchange solid-phase extraction column, measuring by a liquid chromatography-tandem mass spectrometer provided with an ESI source, and carrying out accurate qualitative and quantitative analysis on residues of the four antiviral drugs in eggs. The method provided by the invention has high specificity, can accurately and simultaneously measure residual quantity of amantadine, rimantadine, ribavirin and moroxydine without pollution, has high sensitivity, and provides technical support for guaranteeing quality safety of eggs.

The present invention discloses a synthetic method of N-rimantadine. Adamantanamine hydrochloride or admantadine is dissolved in water and / or water-soluble organic solvent, and then, formalin is added to make methylenation reaction; after the methylenation reaction is end, generated admantadine amine-methylene are dissolved into the ater-soluble organic solvent after being extracted, separated and washed, and sodium borohydride is added to make reduction reaction to obtain a N- rimantadine crude product by separation after the reduction reaction; and the N- rimantadine crude product is purified. A synthetic method of organic compound replaced by single methyl of hydrogen on admantadine with high selection and high generation rate is obtained by the reaction provided by the present invention. The reaction conditions are worm, and a noble metal catalyst and a tetrahydro lithium aluminum reducing agent are avoided to use.

This invention concerns adamantanamines (e.g. memantine, amantadine, and rimantadine) and neramexane salts of thiomolybdic and thiotungstic acids, including their preparation and pharmaceutical compositions, as dual acting drugs. These salts are used to treat or potentially arrest the neurodegenerative pathophysiology, clinical signs and symptoms of dementia of the Alzheimer's type, Parkinson's, Huntington's, AIDS-related dementia and Schizophrenia and its cognitive deficits. Additional uses of these derivatives include antiviral activity. The novel compositions of the present invention appear particularly useful in enhancing the therapeutic benefits of copper-sequestering tetrathiomolybdates in treating elevated copper-induced toxicities in neurologically presenting Wilson's disease, and in treating diseases of the inflammatory etiology and abnormal copper biochemistry, such as tumor angiogenesis, liver cirrhosis, hepatitis, pulmonary fibrosis and other fibrotic diseases, cardiovascular disease, cerebral ischemia, renal anemia, rheumatoid arthritis, diabetes, obesity, gastrointestinal disorders, and eye diseases such as glaucoma, proliferative diabetic retinopathy, and age related macular degeneration. These compounds have excellent stability and aqueous solubility for good oral bioavailability.

The present invention relates to targets for Human microRNAs in Avian Influenza Virus (H5N1) Genome and provides specific miRNA targets against H5N1 virus. Existing therapies for Avian flu are of limited use primarily due to genetic re-assortment of the viral genome, generating novel proteins, and thus escaping immune response. In animal models, baculovirus-derived recombinant H5 vaccines were immunogenic and protective, but results in humans were disappointing even when using high doses. Currently, two classes of drugs are available with antiviral activity against influenza viruses: inhibitors of the M2 ion channel, amantadine and rimantadine, and inhibitors of neuraminidase, oseltamivir, and zanamivir. There is paucity of information regarding effectiveness of these drugs in H5N1 infection. These drugs are also well known to have side effects like neurotoxicity. Thus there exists a need to develop alternate therapy for targeting the Avian flu virus (H5N1). The present invention addresses this need in the field.

The invention relates to a veterinary pharmaceutical composition and a preparation method thereof. The veterinary pharmaceutical composition of the invention is a vaccine oral solution for the prevention and the treatment of bird flu of domestic animal and fowl, and is prepared by the raw materials according to the following parts by weight: 10 to 20 parts of forsythia suspensa, 10 to 25 parts of asarum, 5 to 20 parts of ilex pubescens, 15 to 30 parts of rhizoma anemarrhenae, 8 to 20 parts of wild chrysanthemum, 10 to 20 parts of polygalae, 10 to 25 parts of lobelia chinensis, 2 to 5 parts of snake galls, 10 to 25 parts of ox to gall, 40 to 60 parts of aloe, 25 to 40 parts of rock sugar, 5 to 15 parts of rimantadine and 3 to 10 parts of azithromycin. The oral solution of the invention can be directly used as daily feed for feeding domestic animals and fowl, which can effectively inhibit bird flu virus, reduce the infection rate of respiratory tract and lung and prevent domestic animal and fowl from being infected by bird flu.

The invention discloses a synthetic method for rimantadine. The synthetic method is characterized by comprising the following steps: firstly, obtaining 1-bromoadamantane by reacting adamantine with liquid bromine; then, acidifying to obtain adamantanecarboxylic acid after reacting 1-bromoadamantane with magnesium and anhydrous ether; obtaining adamantine carbonyl chloride by performing reflux reaction on tehadamantanecarboxylic acid with thionyl chloride; obtaining adamantane methyl ketone by reacting the adamantine carbonyl chloride with (CH3)2CdCu; and finally, obtaining the rimantadine by hydriding and reacting adamantane methyl ketone with hydrochloric acid and ammonia water in the presence of sodium borohydride. The synthetic method disclosed by the invention is gentle in condition, simple in follow-up processing, high in yield, cheap in raw material and low in synthesis cost.

The present invention discloses a specific monoclonal antibody capable of recognizing amantadine and rimantadine, wherein the specific monoclonal antibody is secreted by a hybridoma cell line 2G3, and the hybridoma cell line 2G3 is preserved in China Center for Type Culture Collection, and has the preservation number of CCTCC NO:C201625. The invention further discloses an enzyme-linked immunosorbent assay method for detecting the amantadine residue and the rimantadine residue in edible animal tissues, and a kit thereof. According to the present invention, the prepared monoclonal antibody has advantages of high sensitivity, high detection accuracy, good precision, gradual change, rapidness, easy operation and the like, and overcomes the gap in the ELISA method on the market.

The invention discloses an amine compound, a preparation method thereof and application of the amine compound in preparation of anti-influenza virus medicine. The structure of the amine compound is shown in formula (I) (referring to the Specification). According to the invention, two novel framework M2 ion channel inhibitors are identified for the first time, have completely different structures compared with the existing amantadine and rimantadine, may restrain and interdict influenza viruses through a novel mechanism of action, and overcome the defects of amantadine and rimantadine such as ineffective to B-type influenza virus, obvious side effect and cross resistance, so as to provide more medicine choices for clinical anti-influenza.

The invention relates to a structure and purpose of an anti-influenza virus oligonucleotide. Specifically, provided is a structure, a preparation method and purpose of an anti-influenza virus (IV) antisense oligonucleotide of a targeting anti virus programmed cell death protein (PDCD5) which is modified by rimantadine or aliphatic chain. The laboratory utilizes a chemical synthesis method to couple rimantadine or aliphatic chain on a screened anti influenza antisense sequence; an RS-HPLC shows that electronegativity and polarity of the antisense sequence are lowered; a fluorescent labeling method has proved on an A549 cell that the modification promotes absorption of the antisense sequence by the cell; and it is found on an A549 cell and an MDCK cell that the modification can enhance antisense sequence activities on resisting cytopathic effect caused by influenza A viruses H1N1 and H3N2 and ethylamine drug resistant strain H3N2. Therefore, the invention relates to a novel nucleic acid medicament improvement method, which utilizes chemical modification to reduce nucleic acid medicament polarity, increase nucleic acid medicament bioavailability, reduce drugs dose and enhance antiviral curative effect.

The invention relates to a composition and the preparation method for livestock, poultry and aquatic animals. The virus disease vaccine oral liquid comprises the following materials according to the weight account: loosestrife 12 to 25 parts, humifuse euphorbia 15 to 25 parts, tuber of dwarf lilyturf 10 to 20 parts, phyllanfhus 5 to 20 parts, bitter almond 10 to 25 parts, prunella vulgaris 15 to 25 parts, balloonflower 10 to 20 parts, snake gall 2 to 5 parts, ox gall 10 to 20 parts, aloe 40 to 60 parts, crystal sugar 25 to 40 parts, rimantadine 5 to 10 parts, ribavirin 10 to 15 parts, and colistin 10 to 20 parts. The composition has the advantages of ability to reinforce antibody immunity, to relieve mutual interference among vaccines, and to reinforce the immune effect of the vaccine, and convenient drinking water and administration, high absorptivity, wide distribution, no drug residue or poison or side effect, and wide safety range.

The present invention discloses a synthetic method of N-rimantadine. Adamantanamine hydrochloride or admantadine is dissolved in water and / or water-soluble organic solvent, and then, formalin is added to make methylenation reaction; after the methylenation reaction is end, generated admantadine amine-methylene are dissolved into the ater-soluble organic solvent after being extracted, separated and washed, and sodium borohydride is added to make reduction reaction to obtain a N- rimantadine crude product by separation after the reduction reaction; and the N- rimantadine crude product is purified. A synthetic method of organic compound replaced by single methyl of hydrogen on admantadine with high selection and high generation rate is obtained by the reaction provided by the present invention. The reaction conditions are worm, and a noble metal catalyst and a tetrahydro lithium aluminum reducing agent are avoided to use.

A compound is provided that has the formula (II):where R1 in each occurrence is independently H, or C1-C4 alkyl; R2 is a nullity or CH—CH3, R3 is a nullity or C(O)—R6—NH; R6 is C2-C6 alkyl, (CH2CH2—O)n, or (CH(OH)CH2)n; n is an integer of between 1 and 4; R4 is a nullity or NH—R6—C(O); and R5 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, endocannabinoids 1 & 2, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosyl ester, lactic acid, leucine, tryptophan, glutamic acid.

The invention discloses an antivirus andrographolidume derivative and the preparation thereof. The derivative is a 14-deshydroxy-11, 12-didehydrogenation andrographolidume-3, 19-disuccinic acid half-ester rimantadine salt which consists of 14-deshydroxy-11, 12-didehydrogenation andrographolidume-3, 19-disuccinic acid half-ester and rimantadine. The combination ratio of the 14-deshydroxy-11, 12-didehydrogenation andrographolidume-3, 19-disuccinic acid half-ester and the rimantadine is 1:2 or 1:1. The dosage form can be any one of the existing medical dosage forms which are injection solution, transfusion, powder injection, dropping pills, tablets, dispersible tablets, sustained-release tablets, fast disintegrating oral tablets, capsule, soft capsule, granules, emulsion and targeting preparation. The preparation is used for treating upper respiratory tract infection, pneumonia, bronchitis, influenza, and the like, and has obvious effect of improving respiratory state, antibiosis, antipyretic action, antiviral effect and the like. The preparing process is simple and the medicine quality is steady.

The invention belongs to the technical field of substance detection, and particularly provides a method for detecting amantadine and rimantadine in tomatoes. According to the method, a PSA adsorbent, a C18 adsorbent and anhydrous magnesium sulfate are adopted as purification reagents, impurities which interfere with a target object in an extract solution can be adsorbed, the technical problem that matrix interference is serious is solved, and the detection accuracy is improved; and by adopting liquid chromatography-tandem mass spectrometry detection, the sensitivity of the detection method is greatly improved. The detection method provided by the invention is less in used solvent and low in cost. Furthermore, the accuracy, the precision and the sensitivity of the detection method are improved by further limiting liquid chromatography-tandem mass spectrometry detection parameters.

The invention discloses a method for measuring content of 11 illegally added medicaments in veterinary drug powder. The method comprises the following steps of (1) pre-treating veterinary drug powder to be measured by adopting an organic solvent ultrasonic extraction method, wherein an organic solvent is methanol-water, and a volume ratio of methanol to water is (0.9-1.1):(0.9-1.1); (2) detecting olaquindox, ribavirin, amantadine, rimantadine, dexamethasone, chloramphenicol, diethylstilbestrol, furaltodone, nitrofurantoin, nitrofural and furazolidone in extract by adopting liquid chromatography-tandem mass spectrometry. According to the method, a sample can be simply pre-treated by adopting methanol / water (50+50) as an extraction reagent for ultrasonic extraction, and can be loaded on a machine for detection after passing through a filter membrane, and a recovery rate is high; the method is lower in detection limit, a detection limit of the olaquindox, ribavirin, amantadine, rimantadine, dexamethasone, chloramphenicol, furaltodone and furazolidone is 50mu g / kg, and a detection limit of the nitrofurantoin, nitrofural and diethylstilbestrol is 100mu g / kg.

The invention discloses a use of rimantadine Schiff base. Rimantadine ethylamine Schiff base was prepared by chlorination of adamantane formic acid with thionyl chloride, alkylation in the presence oftrimethyl aluminum and cerium formate, oximation to ketoxime, reduction with palladium-carbon and aldehyde-amine condensation reaction with cinnamaldehyde to obtain adamantane ethylamine cinnamaldehyde Schiff base. The reaction route of the invention changes the route of synthesizing adamantane methyl ketone, and cerium formate is used for assisting the reaction of trimethyl aluminum, so that thereaction conditions are mild and the by-products are few. The synthesis method has the advantages of simple and feasible process, low catalyst consumption, environmental protection and high product yield. The adamantine Schiff base prepared by the invention has antibacterial activity, antiviral activity and antitumor activity, and can be used in the fields of medicine, daily chemistry, food and the like, and has the potential to be used as an antibacterial agent, an antiviral agent and an antineoplastic agent.

The invention discloses application of cortex magnoliae officinalis in preparing anti-influenza drugs. Through experiments, it is proved that active ingredients of the cortex magnoliae officinalis-traditional Chinese medicine monomer magnolol has the advantages that the magnolol can effectively inhibit influenza virus replication by specifically inhibiting the expression of influenza virus M2 ionchannel protein, and the synergistic enhancement with anti-influenza drugs oseltamivir, amantadine, rimantadine and ribavirin can enhance the anti-influenza effect of the antiviral drugs.

A compound is provided that has the formula (II):where R1 in each occurrence is independently H, or C1-C4 alkyl; R2 is a nullity or CH—CH3, R3 is a nullity or C(O)—R6—NH; R6 is C2-C6 alkyl, (CH2CH2—O)n, or (CH(OH)CH2)n; n is an integer of between 1 and 4; R4 is a nullity or NH—R6—C(O); and R5 is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, membrane translocating peptide, TAT peptides, endocannabinoids 1 & 2, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptide transferrin, glucosyl ester, lactic acid, leucine, tryptophan, glutamic acid.

The invention discloses an antivirus andrographolidume derivative and the preparation thereof. The derivative is a 14-deshydroxy-11, 12-didehydrogenation andrographolidume-3, 19-disuccinic acid half-ester rimantadine salt which consists of 14-deshydroxy-11, 12-didehydrogenation andrographolidume-3, 19-disuccinic acid half-ester and rimantadine. The combination ratio of the 14-deshydroxy-11, 12-didehydrogenation andrographolidume-3, 19-disuccinic acid half-ester and the rimantadine is 1:2 or 1:1. The dosage form can be any one of the existing medical dosage forms which are injection solution, transfusion, powder injection, dropping pills, tablets, dispersible tablets, sustained-release tablets, fast disintegrating oral tablets, capsule, soft capsule, granules, emulsion and targeting preparation. The preparation is used for treating upper respiratory tract infection, pneumonia, bronchitis, influenza, and the like, and has obvious effect of improving respiratory state, antibiosis, antipyretic action, antiviral effect and the like. The preparing process is simple and the medicine quality is steady.

The invention provides a retarder for the oil well cement, a preparation method thereof and the application thereof, and relates to a retarder for the oil well cement. The retarder for the oil well cement is characterized by comprising the following components in weight part: 100 parts of water, 8-10 parts of 1-rimantadine, 10-12 parts of phosphorous acid, 10-12 parts of 36 to 38 wt% of formaldehyde solution, 3-5 parts of sodium glucoheptonate dihydrate, and 1-3 parts of 36 to 38 wt% of concentrated hydrochloric acid. The invention also relates to the preparation method and the application of the retarder.

The invention relates to a UPLC-MS / MS (Ultra Performance Liquid Chromatography-Mass Spectrometry / Mass Spectrometry) detection method for multiple medicines added in traditional Chinese veterinary medicine powder, and belongs to the technical field of detection methods for medicines added in traditional Chinese medicines. According to the method, the defects of microscopic identification and thin-layer identification are broken through, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS / MS) is adopted, parent ions and daughter ions are optimized, and mass spectrometry parameters are adjusted, 10 illegally added drugs such as amoxicillin, penicillin-V, ampicillin, ceftiofur hydrochloride, oxacillin, cloxacillin, valnemulin, metronidazole and rimantadine can be qualitatively and quantitatively detected. According to the method, parent ions and specific daughter ion fragments are used as identity characteristics of different compounds, uniqueness and specificity are achieved, the sensitivity is one thousandth to one ten thousandth of that of a liquid chromatography method, and the detection limit is low.

The invention relates to a veterinary pharmaceutical composition and a preparation method thereof. The veterinary pharmaceutical composition of the invention is a vaccine oral solution for the prevention and the treatment of bird flu of domestic animal and fowl, and is prepared by the raw materials according to the following parts by weight: 10 to 20 parts of forsythia suspensa, 10 to 25 parts ofasarum, 5 to 20 parts of ilex pubescens, 15 to 30 parts of rhizoma anemarrhenae, 8 to 20 parts of wild chrysanthemum, 10 to 20 parts of polygalae, 10 to 25 parts of lobelia chinensis, 2 to 5 parts ofsnake galls, 10 to 25 parts of ox to gall, 40 to 60 parts of aloe, 25 to 40 parts of rock sugar, 5 to 15 parts of rimantadine and 3 to 10 parts of azithromycin. The oral solution of the invention canbe directly used as daily feed for feeding domestic animals and fowl, which can effectively inhibit bird flu virus, reduce the infection rate of respiratory tract and lung and prevent domestic animaland fowl from being infected by bird flu.

The invention discloses an LCMS / MS determination method for the residual quantity of rimantadine in an egg. The method comprises the following steps: extracting and purifying an egg sample, preparinga standard solution, determining the sample and the like. A sample pretreatment method which is simple, convenient, rapid and capable of effectively avoiding matrix interference in a sample is established, the pretreatment method is combined with LCMS / MS to be applied to qualitative confirmation and quantitative detection of rimantadine in the egg, the average recovery rate is 87.43%-96.74%, the average relative standard deviation (RSD) is 0.12%-0.45% (intra-batch) and 0.04%-0.23% (inter-batch), the detection limit is 0.3 [mu]g / kg, and the limit of quantitation is 1 [mu]g / k. The method has theadvantages of simplicity and convenience in operation, quickness, accuracy, high sensitivity and good repeatability.

The invention discloses a synthesis method of rimantadine Schiff base. The synthesis method comprises the following steps: preparation of adamantane formyl chloride, preparation of adamantane methyl ketone, preparation of 1-adamantane methyl ketoxime, preparation of rimantadine and preparation of rimantadine Schiff base, wherein the preparation of adamantane methyl ketone comprises the following steps: adding trimethylaluminum and cerium formate into a flask; dropwise adding a benzene solution of adamantane formyl chloride so that the adamantane formyl chloride reacts with the trimethylaluminum to generate adamantane methyl ketone; after the reacting, pouring the reaction liquid into ice water, then filtering and drying to obtain light yellow precipitate which is adamantane methyl ketone.The synthesis method disclosed by the invention has the following beneficial effects: the reaction route changes the route of synthesizing adamantane methyl ketone before; by adopting cerium formate to assist in the trimethylaluminum reaction, the reaction conditions are mild, and few byproducts are generated. The synthesis method disclosed by the invention has the advantages of mild conditions, simple and feasible technology, small dosage of catalyst, environmental friendliness and high product yield.