73 results about "Pregabalin" patented technology

The invention provides a pregabalin slow-release type dissolving microneedle patch based on PLGA microspheres as well as a preparation method and application thereof. The method comprises the following steps: dissolving pregabalin and hyaluronic acid in deionized water to form an inner water phase (W1); dissolving PLGA in dichloromethane to form an organic phase (O); performing ultrasonic emulsification on the internal water phase and the organic phase to form W / O primary emulsion; rapidly adding the primary emulsion into an external water phase (W2) containing PVA and NaCl to form a W1 / O / W2 type multiple emulsion, and then carrying out solvent evaporation curing, centrifugal washing and freeze drying to obtain PLGA (at) PG microspheres; and uniformly dispersing the PLGA (at) PG microspheres in a hyaluronic acid solution, adding into a microneedle mold, vacuumizing, centrifuging, drying, and demolding the microneedle to obtain the dissolution type microneedle patch. By optimizing microsphere preparation, drug sustained release and microneedle patch preparation technologies are realized, and an efficient, safe and continuous local delivery platform is provided.

The invention discloses an olefin reductase, a coding gene, a carrier, an engineering bacterium and an application of the olefin reductase. An olefin reductase SeER mutant is obtained by carrying out single-point or multi-site site-directed mutagenesis or site-directed saturation mutagenesis on the 38th site, the 117th site, the 248th site, the 293th site and the 373th site of an amino acid sequence shown in SEQ ID NO.2. The invention provides a series of novel olefin reductase SeER mutants capable of efficiently, stereocomplementarily reducing an olefin compound to prepare a chiral compound, chiral GABA derivative drugs such as phenibuterol, baclofen, tolybuterol, pregabalin and the like are successfully synthesized through a chemical-enzyme coupling method, and compared with an existing method, the novel olefin reductase SeER mutants have the advantages that the novel olefin reductase SeER mutants can be used for efficiently and stereocomplementarily reducing the olefin compound to prepare the chiral compound; the strain disclosed by the invention can flexibly regulate and control the configuration of a product, and is high in stereoselectivity and conversion rate.

The invention discloses a small molecular twin drug compound with a synergistic analgesic effect and a pharmaceutical composition, a preparation method and application thereof. The twin drug molecule is formed by connecting a drug A and a drug B through a covalent bond, the drug A is nefopam, and the drug B is gamma-aminobutyric acid (GABA) and analogues thereof and comprises gabapentin, pregabalin, GABA, melogabalin and crigabalin. The analgesic effect of the composition is superior to that of combined administration and single administration, and the composition can obviously improve various acute and chronic inflammation pains and can relieve paclitaxel-induced peripheral neuralgia; the anti-inflammatory activity is higher than that of combined use and single drug, so that the compound has the potential of treating pain, inflammation and inflammatory pain related diseases; the interaction among the medicines can be effectively reduced, and the medication compliance of a patient is improved.

The present invention provides the use of phenylquinolinone and flavonoid derivatives for neuropathic pain, and the phenylquinolinone and flavonoid derivatives include pharmaceutically acceptable salts thereof. The compound of the present invention is a histamine H3 receptor antagonist, which has a different mechanism of action from existing drugs and can be used in the preparation of drugs for treating neuropathic pain diseases. The effect of the compound of the present invention in treating neuropathic pain is better than amitriptyline, gabapentin, pregabalin and carbamazepine, indicating that the compound of the present invention has a better therapeutic effect, has the characteristics of small dosage, good efficacy, high bioavailability and safety, and compared with opioid drugs, the compound of the present invention is not addictive and is a very effective drug for treating neuropathic pain diseases. Therefore, the clinical application prospects are huge. The general structural formula is as follows:

The present invention discloses a method for recovering pregabalin intermediate 3-isobutylglutaric acid monoamide, the method comprising the following steps: (1) adding a racemate to be eliminated into an organic solvent, gradually heating up, controlling the temperature and pressure to carry out decompression and water separation; (2) after decompression and water separation, heating up under normal pressure, controlling the temperature to 100-140°C, and carrying out a dehydration cyclization reaction; (3) hydrolyzing the product obtained in step (2) under alkaline conditions to obtain a 3-isobutylglutaric acid monoamide racemate. The present invention has obvious advantages in the current safety, environmental protection, quality improvement and efficiency enhancement, and fierce market competition.

The present invention relates to an orodispersible tablet manufactured by a wet granulation method comprising pregabalin or pharmaceutically acceptable salts thereof, at least one disintegrant, at least one diluent, at least one binder, at least one glidant, at least one lubricant, and one or more pharmaceutically acceptable excipients. The orodispersible tablet prepared using these excipients exhibits desirable properties such as facilitating disintegration, and dissolution of the drug for oral administration. Further, the present invention also relates to the process for preparing the said solid pharmaceutical composition.

The application discloses a sustained-release pregabalin composition and a preparation method thereof, and belongs to the technical field of medicine, and specifically relates to a sustained-release pregabalin composition and a preparation method thereof. The sustained-release pregabalin composition comprises the following components in parts by weight: 45-50 parts of pregabalin or a pharmaceutically acceptable salt thereof; 23-35 parts of a matrix forming agent; 23-30 parts of a swelling agent, wherein the swelling agent is a double-layer network structure, a first layer network provides support for a second layer network, and the two are crosslinked in a physical and chemical manner; 15-25 parts of a sustained-release agent; and 12-20 parts of a filling agent. The first layer network comprises chitosan, sodium alginate, methacrylic anhydride, a photoinitiator and zinc ions; and the second layer network comprises cyclodextrin, polyethylene glycol dimethacrylate, methacrylamide, a crosslinking agent, a photoinitiator and deionized water. The sustained-release tablet of the application is expanded to more than 13 mm after 1.5 h, and the tablet can remain intact, which is beneficial to the retention of the sustained-release pregabalin composition in the stomach, achieves the effect of sustained release, and improves the absorption of pregabalin.

The invention relates to the technical field of veterinary drugs, and particularly provides a pregabalin oral liquid and a preparation method thereof. Each 100ml of the pregabalin oral liquid comprises 10 to 35g of a pregabalin solid dispersion, 0.01 to 1g of a flavoring agent, 0.01 to 2g of a preservative, a pH regulator and water, and the pH value of the pregabalin oral liquid is 4.5 to 5.5. The pregabalin oral liquid is high in stability, strong in compliance, high in bioavailability and good in clinical effect.

The invention discloses a pregabalin capsule which comprises the following raw materials in parts by weight: 7-9 parts of pregabalin, 12-21.6 parts of a filling agent, 0.5-1.5 parts of a lubricating agent and 90-110 parts of a gelatin hollow capsule, wherein the filling agent is a mixture of acetylated corn starch and lipidosome coated lactose. The pregabalin capsule is used for solving the technical problem that the stability of the pregabalin capsule is poor.

The invention discloses an RP-HPLC-RID method for detecting the (R)-isomer of pregabalin, belonging to the field of drug analysis. The method uses a polysaccharide derivative coated chiral reversed-phase chromatographic column and a differential refractometer to directly and effectively separate pregabalin and the (R)-isomer, and the detection result has good accuracy and high sensitivity. Compared with the existing evaporative light scattering detector method and pre-column derivatization reversed-phase chromatography method, the method is simpler to operate, has lower cost and is more environmentally friendly. The invention provides a better guarantee for the quality control of pregabalin and its preparations.

The invention relates to a method for detecting antiepileptic drugs in serum based on polarity conversion UPLC-MS / MS. The antiepileptic drugs (AEDs) are respectively levetiracetam, pregabalin, gabapentin, lamotrigine, phenobarbital, oxcarbazepine, phenytoin sodium, carbamazepine, clonazepam, diazepam and sodium valproate. Simplifying sample pretreatment by adopting a methanol (containing formic acid) one-step extraction method; in the chromatographic analysis, C18 is used as a chromatographic column and a pre-column, a 5% methanol aqueous solution (containing formic acid)-95% methanol aqueous solution (containing formic acid) is used as a mobile phase, gradient elution is carried out, and the mass spectrum adopts an MRM mode. The method has the advantages of being high in sensitivity, good in precision and accuracy, easy to operate, free of matrix interference and the like, can be used for measuring serum AEDs of different species, and provides technical support for the prevention and treatment mechanism of epilepsy drugs, clinical AEDs blood concentration monitoring, individualized drug delivery scheme formulation and pharmacokinetic research.

This invention discloses bridged tricyclic γ-aminobutyric acid (GABA) derivatives targeting the α2δ subunit of voltage-gated calcium channels. These compounds exhibit enhanced binding affinity and improved pharmacological profiles. They aim to overcome limitations of current α2δ ligands like gabapentin and pregabalin. The new derivatives show potential for treating neuropathic pain, epilepsy, and related disorders.

The present invention relates to a synthesis method for a pregabalin intermediate, which effectively improves the reaction yield and the product purity, significantly reduces the impurity content and is suitable for large-scale industrial production.

Described herein are method of treating pain associated with osteoarthritis (OA) using a low dose of an oral drug conjugate of naproxen and pregabalin. Described herein are method of addressing sleep disturbance in a subject in pain using an oral drug conjugate of naproxen and pregabalin.

The present invention relates to a topical pharmaceutical composition comprising pregabalin and a reduced micellar phospholipid as an active ingredient, which results in a prolonged analgesic effect of pregabalin. The product can reduce neuropathic pain by at least 5 hours.

Compositions, kits and systems containing pregabalin haptens, immunogens and / or protein conjugates are disclosed. Methods of producing and using the pregabalin haptens, immunogens, and conjugates are also disclosed.

This invention relates to the fields of genetic engineering and protein modification technology, specifically to a lipase mutant and its application in the synthesis of a key chiral intermediate of pregabalin. This invention relates to *Thermophilus spp.* (…). Thermomyces lanuginosus Based on lipase TL, through extensive mutation screening, a lipase mutant with significantly improved catalytic efficiency for the hydrolysis of ethyl 2-carboxyethyl-3-cyano-5-methylhexanoate (CNDE) was finally obtained. Among them, the single-point mutant containing S254A has a catalytic constant... K The cat value reached 100.2, which is 45 times that of the wild type, and the enantioselectivity ee value was also higher than that of the wild type, achieving unexpected technical results. This lipase mutant has broad prospects for the efficient synthesis of key chiral intermediates of pregabalin.

The present disclosure describe a simple optimized method that allows the combined manufacture of five active substances: cyanocobalamin, pyridoxine, thiamine, pregabalin and celecoxib in a single solid, stable, immediate release pharmaceutical form for pain. The combined use of drugs that act at distinct levels is associated with greater pain relief and, as they can be used at lower doses, with a reduced risk of adverse effects. In this context, the combined use of B vitamins plus pregabalin and celecoxib would be associated with greater analgesic activity through complementary action mechanisms.

Disclosed are a pregabalin artificial hapten, artificial antigen and preparation method therefor and application thereof. The structure of the pregabalin artificial hapten is shown as formula (I) and structure of the pregabalin artificial antigen is shown as formula (II). The application is in the preparation for anti-pregabalin antibodies with the pregabalin artificial antigen. The pregabalin artificial hapten retains the characteristic structure of pregabalin to the greatest extent, and has an active group that can be coupled with a carrier protein, and can be used as an antigenic determinant; the pregabalin artificial antigen obtained by further preparation can immune to obtain anti-pregabalin antibodies with high affinity, high sensitivity and strong specificity. The titer of the immune serum obtained by immunizing New Zealand white rabbits is as high as 1:90000, which can be used for rapid and accurate immunoassay of pregabalin.

The invention discloses a twin drug with analgesic effect and application thereof, the twin drug is formed by connecting a drug A and a drug B through a chemical bond, the drug A is a TRPV1 agonist, and the drug B is lipoic acid, pregabalin, gabapentin, melogabalin or clinigabalin. Meanwhile, the invention also comprises a preparation method of the twin drug, and application of the twin drug or pharmaceutically acceptable salts and compositions thereof in preparation of drugs for preventing and treating pains or nervous system diseases. The twin drug can significantly improve the water solubility of the TRPV1 agonist, has a long-acting analgesic effect on different types of pains such as inflammatory pains and neuralgia, and has an analgesic effect superior to that of a composition of the two components and then superior to that of a single component. Meanwhile, twin drugs show a more lasting analgesic effect and have a good application prospect.

The invention provides attapulgite modified gel. The attapulgite modified gel is prepared from the following raw materials: attapulgite, pregabalin, sodium alginate, carboxymethyl cellulose, calcium carbonate and D-glucolactone. The attapulgite, the sodium alginate and the carboxymethyl cellulose are mixed and cross-linked, the unique layer chain crystal structure of the attapulgite endows the gel with excellent adhesion and mechanical properties, so that the gel can be tightly attached to skin or tissues, and meanwhile, the attapulgite, the sodium alginate and the carboxymethyl cellulose have a synergistic effect to construct a stable three-dimensional network with a pore structure; the pregabalin hydrogel prepared by the preparation method disclosed by the invention is favorable for improving the continuous release performance of the gel to pregabalin, reducing the burst release phenomenon of pregabalin in application, prolonging the drug effect time of the hydrogel and meeting clinical treatment requirements.

Provided is an engineered polypeptide capable of catalyzing the asymmetric hydrolysis of 3-isobutylglutarimide to generate (R)-(−)-3-(carbamoylmethyl)-5-methylhexanoic acid. The engineered polypeptide has high stereoselectivity, high catalytic activity, good process stability and thermal stability, and tolerance to high product concentrations, and has good prospects for industrial applications.

The invention discloses an olefin reductase SeER mutant and application thereof in synthesis of chiral drugs, and provides a series of novel olefin reductase SeER mutants capable of efficiently and asymmetrically reducing beta-alkyl / aryl-beta-cyanoacrylate compounds, and the olefin reductase SeER mutants have high conversion rate (gt; 99% conversion rate), good enantioselectivity (gt; 99% ee), the substrate range is wide (gt; according to the present invention, the screened olefin reductase SeER mutant can be successfully synthesized into the chiral GABA derivative drugs such as pregabalin and brivaracetam through the chemical-enzyme coupling method, such that the overall reaction yield is improved, and the route is simple;

The invention relates to the technical field of gene engineering and protein modification, in particular to a lipase mutant and application thereof in synthesis of a pregabalin key chiral intermediate. According to the invention, on the basis of thermomyces lanuginosus lipase TL, a large amount of mutation screening is carried out, so that the lipase mutant of which the catalytic efficiency of hydrolysis of 2-carboxyethyl-3-cyano-5-methyl ethyl hexanoate (CNDE) is remarkably improved is finally obtained. Wherein the catalytic constant Kcat of the single-point mutant containing S254A reaches 100.2 and is 45 times of that of a wild type, the enantiomer selectivity ee value of the single-point mutant containing S254A is also higher than that of the wild type, and an unexpected technical effect is achieved. The lipase mutant can be applied to efficient synthesis of a pregabalin key chiral intermediate, and has a wide prospect.

The application discloses an olefin reductase, a coding gene, a carrier, an engineering bacterium and application thereof, wherein the olefin reductase SeER mutant is obtained by single-point or multi-point site-directed mutation or site-directed saturation mutation of the 38th, 117th, 248th, 293rd and 373rd sites of the amino acid sequence shown in SEQ ID NO. 2. The application provides a series of new olefin reductase SeER mutants capable of efficiently stereocomplementary reduction of olefin compounds to prepare chiral compounds, and successfully synthesizes chiral GABA derivative drugs such as phenibut, baclofen, tolperisone and pregabalin through a chemical-enzyme coupling method. Compared with existing methods, the strain can flexibly regulate the configuration of the product, and has high stereoselectivity and conversion rate.

This application relates to the field of veterinary drug formulation technology, and discloses a cat anti-stress oral formulation containing pregabalin and its preparation method. The raw materials include: pregabalin-L-arginine co-ground micronized powder, isostearic acid, medium-chain triglycerides, hydrophobic fumed silica, and anhydrous yeast extract powder. The preparation method includes the following steps: weighing each raw material by mass; dissolving isostearic acid in medium-chain triglycerides by heating and stirring; starting high-speed dispersion under vacuum and constant temperature; introducing pregabalin-L-arginine co-ground micronized powder for reaction; introducing anhydrous yeast extract powder for dispersion; cooling and switching to low-speed stirring; adding hydrophobic fumed silica and running under vacuum; finally, static aging and packaging to obtain the finished product. This invention employs a technical solution of compounding pregabalin-L-arginine co-ground micronized powder, isostearic acid, and hydrophobic fumed silica in the oil phase, achieving the technical effect of thixotropic formulation and long-term static non-sedimentation.

The present invention provides a pharmaceutical composition for preventing and / or treating neuropathic pain or complications, wherein the active ingredients of the pharmaceutical composition include an artemisinin compound and pregabalin, wherein the artemisinin compound is selected from one or more of dihydroartemisinin, artemether and artesunate, preferably dihydroartemisinin. The combined use of dihydroartemisinin and pregabalin of the present invention has obvious advantages in treating the core symptoms of neuropathic pain, reducing drug side effects and reducing drug tolerance.

The invention belongs to the technical field of pet medicines, and discloses an oral pregabalin paste for pets, which comprises pregabalin, a thickening agent, an acidity regulator, a phagostimulant and water, the pH value of the paste is 3-4; the concentration of pregabalin in the paste is not more than 5wt%. Compared with a traditional pregabalin water aqua medicine, the pregabalin oral administration paste provided by the invention has the advantages that the stability of pregabalin can be improved, and the pregabalin oral administration paste still has relatively good stability in a normal temperature state; besides, the palatability of the pregabalin is greatly improved and the convenience of pet administration is improved by screening the phagostimulant in a specific combination and combining the characteristic that the paste is convenient for pet administration.

The present invention relates to a topical pharmaceutical composition comprising pregabalin and a reduced micellar phospholipid as an active ingredient, which results in a prolonged analgesic effect of pregabalin. The product can reduce neuropathie pain by at least 5 hours.

The invention relates to a preparation method of hydrogel loaded with lidocaine hydrochloride and pregabalin and the hydrogel. The preparation method comprises the following steps: mixing hyaluronic acid, dopamine hydrochloride and pure water to prepare a solution A, and then preparing a nano cellulose suspension through an ultrasonic dispersion and magnetic stirring method; the preparation method comprises the following steps: preparing a nano-cellulose suspension, mixing and stirring lidocaine hydrochloride, pregabalin, carboxymethyl chitosan and the nano-cellulose suspension to prepare a solution B, mixing the solution A with the solution B, and carrying out step-by-step oxidation crosslinking treatment to finally obtain the hydrogel loaded with lidocaine hydrochloride and pregabalin. According to the invention, the mechanical strength and adhesion strength of the hydrogel are improved, the drug loading rate, drug loading stability and release controllability are ensured, and the synergistic treatment effect of first rapid analgesia and then long-acting nerve regulation is realized.