51 results about "Citicoline" patented technology

The present invention relates to a novel association or combination of active ingredients useful in the prevention and repair of neuronal damage, both centrally and peripherally. In greater detail, the present invention relates to an association or combination of i) an extract of Gastrodia elata and ii) at least one ingredient selected from the group comprising or, alternatively, consisting of citicoline, L-acetylcarnitine and, preferably, at least one vitamin of group D, and / or mixtures thereof, and / or at least one vitamin of group B, and / or mixtures thereof. Furthermore, the invention also relates to the pharmaceutical compositions and / or compositions for medical devices (Regulation (EU) 2017 / 745) and / or nutraceutical and / or food compositions comprising that association and to their use in therapy, in particular in the protection of the functionality of the nervous system and in the prevention and / or treatment of central and peripheral neuropathies.

The invention belongs to the field of bioengineering, and particularly relates to phosphorylcholine cytidyltransferase and application thereof in preparation of citicoline, and the specific application is that the phosphorylcholine cytidyltransferase can efficiently catalyze phosphorylcholine and CTP to react to generate citicoline. The phosphorylcholine cytidyltransferase is prepared by the following steps: synthesizing a coding gene of the phosphorylcholine cytidyltransferase, selecting pHT01 as an expression vector, co-expressing with choline kinase, transforming into host bacteria, and inducing protein expression. According to the choline phosphate cytidyltransferase disclosed by the invention, under the same reaction condition and within the same reaction time, the yield of a citicoline product obtained by conversion is higher than that of choline phosphate cytidyltransferase (ScCCT) which is most commonly used in the market at present and is derived from saccharomyces cerevisiae S288c. Specifically, the yield of the MsCCT001 is 10 times higher than that of the ScCCT, the yield of the MbCCT006 is 6 times higher than that of the ScCCT, and the yield of the MeCCT008 is 8 times higher than that of the ScCCT.

The invention discloses escherichia coli recombinant engineering bacteria for producing citicoline as well as a construction method and application of the escherichia coli recombinant engineering bacteria, and belongs to the technical field of biology. A genome cytidine deaminase coding gene cdd is knocked out on the basis of Escherichia coli K-12 MG1655, a temperature control expression vector PBV220 is used for expressing a SpnCCT-SpnCKI-pRpLpyrG mutant gene cluster, the expression of choline transporter protein BetT is enhanced, the gene locus of Escherichia coli ptsH-ptsI-crr is destroyed, meanwhile, a glucose permease gene glf and a glucokinase gene glk from Zymomonas mobilis are introduced, and the mutant gene cluster of the Escherichia coli K-12 MG1655 is obtained. The escherichia coli recombinant engineering bacterium ZMCB02NCL capable of efficiently biosynthesizing citicoline is obtained, and the preservation number of the escherichia coli recombinant engineering bacterium ZMCB02NCL is CCTCC NO: M 2025483.

Provided is an “all natural” biologic-enhancing beverage (BioBeverage), which contains, in addition to purified water, electrolytes, vitamins, anti-oxidants, micronutrients, natural fruit infusion, natural sweetener to improve taste, enhance GI Biome viability, provide antimicrobial benefits and reduce oxidative stress, Citicoline, to enhance brain / neurologic function, neurologic maintenance, repair and regeneration, CoQ10, to enhance cardiovascular energy and health, Hydroxyproline, to enhance connective tissue maintenance, repair and regeneration, and a niacinamide adenine dinucleotide (NAD+) precursor to promote overall health, including neurologic, cardiovascular and connective tissues maintenance and repair, and if present, reduce risks and symptoms of multiple neurodegenerative disorders by maintenance of healthy mitochondrial function.

The application provides a candidate drug for promoting embryo implantation efficiency of patients with uterine redox imbalance type RIF, and belongs to the technical field of embryo implantation. In order to solve the problem of how to find potential intervention drugs for the pathological mechanism of uterine redox imbalance type RIF, a five-step high-efficiency drug screening strategy based on an in-vitro implantation model of uterine redox imbalance type repeated embryo implantation failure is adopted to ensure the reliability and functional correlation of the screening results. The candidate drug screened by the five-step high-efficiency drug screening strategy includes any one of the following drugs: avobenzone, vasopressin, ethylenediaminetetraacetic acid dipotassium, larotrectinib sulfate, citicoline, opicapone, iclapa, L-leucine, fulvestrant, malic acid and lucotinib. Among these candidate drugs, avobenzone, vasopressin and ethylenediaminetetraacetic acid dipotassium are the best three drugs for promoting the implantation efficiency of patients with uterine redox imbalance type RIF.

The present invention relates to an ophthalmological composition, comprising at least one nicotinic acetylcholine receptor (nAChR) modulator, in particular varenicline, mecamylamine and derivatives, and / or at least one substance of the endogenous Kennedy metabolic pathways, as well as salts and derivatives or pharmaceutically acceptable salts of these substances, and choline-containing phospholipids, salts and derivatives of these substances. From these groups, particular preference is given to choline, phosphocholine, CDP-choline (citicoline), phosphatidylcholine (for example lecithin having a phosphatidylcholine content ≥ 80 wt.%, for example soy lecithin), ethanolamine, phosphoethanolamine, CDP-ethanolamine, phosphatidylethanolamine, L-α-glycerylphosphorylcholine, phosphatidylcholine, and phosphatidylethanolamine.

The invention discloses a method for promoting the synthesis of cytidine triphosphate, belonging to the field of genetic engineering and microbial engineering. The present invention knocks out the dCTP deaminase gene dcd, the phosphate nucleoside kinase gene ndk, the ribonucleoside triphosphate reductase gene nrdD, the phosphate nucleoside pyrophosphohydrolase gene mazG, and the 5'-CMP diphosphohydrolase gene nudG of Escherichia coli by gene knockout technology, and obtains an Escherichia coli mutant that can accumulate cytidine triphosphate. Further by overexpressing the orotate phosphoribosyltransferase gene pyrE, the yield of CTP is increased, and the CTP level can reach more than 21.9mg / L. This method for promoting the synthesis of cytidine triphosphate and the high-efficiency Escherichia coli strain obtained can be used to realize the industrial production of CTP and its derivatives (such as citicoline, etc.), which is beneficial to reduce its production cost and environmental pollution, and realize green biomanufacturing.

Pharmaceutical compositions are disclosed in the form of orosoluble suckable and chewable tablets consisting of citicoline, nicotinamide and pharmaceutically acceptable excipients, for use in the prevention and / or treatment of degeneration of the optic nerve and retinal nerve cells resulting from glaucoma.

Provided is an "all natural" biologic-enhancing beverage (BioBeverage), which contains, in addition to purified water, electrolytes, vitamins, anti-oxidants, micronutrients, natural fruit infusion, natural sweetener to improve taste, enhance GI Biome viability, provide antimicrobial benefits and reduce oxidative stress, Citicoline, to enhance brain / neurologic function, neurologic maintenance, repair and regeneration, CoQ10, to enhance cardiovascular energy and health, Hydroxyproline, to enhance connective tissue maintenance, repair and regeneration, and a niacinamide adenine dinucleotide (NAD+) precursor to promote overall health, including neurologic, cardiovascular and connective tissues maintenance and repair, and if present, reduce risks and symptoms of multiple neurodegenerative disorders by maintenance of healthy mitochondrial function.

The invention provides a candidate medicine for promoting the embryo implantation efficiency of a uterus redox imbalance type RIF patient, and belongs to the technical field of embryo implantation. In order to solve the problem of how to discover a potential intervention drug aiming at a uterine redox imbalance type RIF pathological mechanism, a five-step efficient drug screening strategy based on an in-vitro implantation model of uterine redox imbalance type repeated embryo implantation failure is adopted, so that the reliability and functional correlation of a screening result are ensured. A candidate drug screened by adopting a five-step method efficient drug screening strategy comprises any one of the following drugs: avobenzone, vasopressin, dipotassium ethylene diamine tetraacetate, lalotinib sulfate, citicoline, olprinone, eltrombopag, L-leucine, fulvestrant, malic acid and rucotinib. Among the candidate drugs, avobenzone, vasopressin and dipotassium ethylenediaminetetraacetate are three drugs with optimal implantation promotion efficiency for patients with uterine redox imbalance type RIF.

The present application relates to a kind of cytidine choline dextrohydrotalcid derivatives and its preparation method and application, belong to biological medicine technical field.The present application is aimed at solving the technical problems of low blood-brain barrier penetration rate and limited treatment effect of existing edaravone dextrohydrotalcid compound preparation.The present application prepares a dextrohydrotalcid derivative (C-B) with boronic acid structure, then it is compounded with cytidine choline in specific pH buffer system, and forms cytidine choline dextrohydrotalcid derivative (C-D-B).The present application can effectively improve the efficiency of drug crossing blood-brain barrier by using the dynamic covalent characteristics of boronic ester bond and free radical responsiveness.The experimental results show that, compared with existing combination drug, the derivative of the present application can significantly reduce the infarction area of cerebral ischemia model animal, reduce cell damage and active oxygen level, and promote vascular regeneration, and show better treatment effect on ischemic brain injury.

The invention provides an application of citicoline in preparation of a medicine for treating congenital choline metabolic disorders, and belongs to the technical field of crossing of neuropharmacology and disease model application, the application is directly directed at the core pathology of citicoline deficiency in an SLC44A1 deficiency model, and the core pathology of citicoline deficiency in the SLC44A1 deficiency model is supplemented with deficient substances through clinically marketed medicines, so that the application of citicoline in the SLC44A1 deficiency model is realized. Different from existing non-specific drugs, the intervention pertinence is high; researches show that the citicoline not only can repair myelin sheath defects in the developmental stage, but also can improve myelin sheath disorders and neurological functions continuously existing in the adult stage, the limitation that an existing medicine only relieves symptoms in the acute stage is solved, and the long-term treatment requirement is met.

The present invention relates to a novel association or combination of active ingredients useful in the prevention and repair of neuronal damage, both centrally and peripherally. In greater detail, the present invention relates to an association or combination of an extract of Gastrodia elata, citicoline, L-acetylcamitine, at least one vitamin of group B and at least one vitamin of group D. Furthermore, the invention also relates to the pharmaceutical compositions and / or compositions for medical devices and / or nutraceutical and / or food compositions comprising that association and to their use in therapy, in particular in the protection of the functionality of the central and of the peripheral nervous system.

The present invention relates to a composition for regulating at least one of an intracellular calcium concentration and a calcium-dependent signaling pathway, the composition containing citicoline or a salt thereof. The present invention also relates to a composition for regulating the expression of at least one of a Neuronal Calcium Sensor-1 (NCS-1) gene and a Two Pore Segment Channel 1 (TPCN1) gene, the composition containing citicoline or a salt thereof.　

The present invention relates to pharmaceutical compositions containing Acetylcholine agonist like Cinitapride, Prucalopride, Citicoline, Epibatidine, Lobeline, Cytosine, Cytisinicline for treatment of dry eye syndrome and its related disorders in suitable dosage form. The inventive concept provided herein are methods and pharmaceutical compositions comprising acetylcholine receptor agonist or pharmaceutically acceptable salt thereof by preparing oral dosage forms like Nasal drops, ophthalmic drops, oral mouth liquid spray or sublingual or dispersible dosage form for the management of dry eye syndrome and its associated disorders in suitable dosage form accordingly performing preclinical study to prove the efficacy of acetylcholine receptor agonist.

The present invention provides compositions and dosage forms for enhancing energy and reducing inflammation. In certain embodiments, an energy composition comprises citicoline and paraxanthine in a mass ratio of 10:1 to 1:10, preferably about 1:1, delivered as an oral film, capsule, or liquid; exemplary unit doses deliver about 200–300 mg citicoline and about 200–300 mg paraxanthine. In further embodiments, an anti-inflammatory composition comprises astaxanthin, L‑citrulline, glutathione, luteolin, and palmitoylethanolamide within defined mg ranges. Liposomal and spray‑dried liposomal microparticle formulations, including reconstitution parameters, are provided. The compositions yield synergistic effects relative to individual actives, as quantified by accepted models (e.g., combination index <1). Methods of manufacturing, kits, and methods of improving mental focus, physical performance, and recovery are also described.

The invention provides a citicoline sodium injection and a preparation method thereof, and the citicoline sodium injection comprises the following raw materials by weight: 10-15 parts of citicoline sodium, 3-5 parts of phospholipid, 3-5 parts of astaxanthin, 1-3 parts of vitamin C, 0.5-1.5 parts of citric acid, and 900-1100 parts of a solvent. The preparation method comprises the following specific steps: (1) adding phospholipid and citicoline sodium into an ethanol water solution, carrying out ultrasonic treatment, homogenizing and filtering to obtain nano particles embedded with citicoline sodium; (2) adding the citicoline sodium-embedded nanoparticles into a solvent, sequentially adding astaxanthin and vitamin C, performing ultrasonic stirring, adding citric acid, and continuing stirring to obtain a mixed solution; and filtering the mixed solution, sterilizing and filling. The citicoline sodium injection provided by the invention improves the stability to light and oxygen at the same time, and the embodiment verifies that the character and the pH value of the citicoline sodium injection are stable, the content of citicoline sodium is not changed, related substance impurities are few, and the increase of the impurity speed is slow when the citicoline sodium injection is subjected to continuous illumination for 30 days and is placed in an open dark place at 20 DEG C for 30 days respectively.

The present invention relates to ophthalmic compositions comprising at least one nicotinic acetylcholine receptor (nAChR) modulator, particularly varenicline, mecamillamine, and derivatives, and / or at least one substance of the endogenous Kennedy metabolic pathway, as well as salts and derivatives or pharmaceutically acceptable salts thereof, and choline-containing phospholipids, salts and derivatives thereof. Of these, choline, phosphocholine, CDP-choline (citicoline), phosphatidylcholine (e.g., lecithin with a phosphatidylcholine content of 80% by weight or more, e.g., soy lecithin), ethanolamine, phosphoethanolamine, CDP-ethanolamine, phosphatidylethanolamine, L-α-glycerylphosphorylcholine, phosphatidylcholine, and phosphatidylethanolamine are particularly preferred.

This invention, entitled "A Pharmaceutical Composition, Formulation, Preparation Method, and Application for Alleviating Cerebral Ischemia-Reperfusion Injury," belongs to the field of pharmaceutical technology. The technical problem to be solved is to improve the efficacy of drugs in preventing and / or treating cerebral ischemia-reperfusion injury. The key technical solution is a pharmaceutical composition for alleviating cerebral ischemia-reperfusion injury, comprising sinapic acid and a second therapeutic agent, wherein the second therapeutic agent comprises at least one of edaravone, citicoline, and tetramethylpyrazine.

The present application belongs to the technical field of genetic engineering, and particularly relates to an engineered bacillus subtilis, a preparation method and application thereof. In the present application, in order to improve the supply of precursor cytidine triphosphate (CTP) in the process of fermentation of bacillus subtilis for producing cytidine, first, the feedback-inhibited CTP synthetase PyrG E156K is overexpressed to promote the conversion of uridine triphosphate to CTP; then, the repressor gene of the pyrimidine operon pyrR is knocked out to promote the synthesis of uridine monophosphate, and further promote the synthesis of CTP; finally, the pyrimidine nucleotide degradation genes pdp and cdd are knocked out to block the conversion of uridine / cytidine to uracil / cytosine and the conversion of cytidine to uridine, respectively, reduce the consumption of pyrimidine nucleotides, and further facilitate the intracellular accumulation of CTP. The yield of cytidine of the finally constructed engineering bacteria is about 12.6 times that of the original starting bacteria, and the results of the present application further prove the importance of CTP for cytidine synthesis.

The present invention relates to a composition for promoting the excitation of a neural circuit, the composition containing citicoline, a decomposition product of citicoline, or a salt of citicoline or the decomposition product. The present invention also relates to a composition for promoting the excitation of a neural circuit, the composition containing citicoline or a salt thereof, the composition having such a characteristic property that the excitation promoting effect thereof on the neural circuit wears off within 24 hours.

Compositions and methods are described for improving brain health and cognitive function and for preventing and treating Alzheimer's disease and other age-related dementia diseases and conditions for intake as a dietary or nutritional supplement, for example, as a powdered drink mix. Compositions for providing an energy source to the brain during exercise are also described. The composition includes a source of choline, a source of magnesium, at least one taurine-containing composition, a source of ashwagandha root, and phosphatidylserine. The source of choline can be alpha-glycerylphosphorylcholine or citicoline and the source of magnesium can be magnesium-L-threonate or magnesium glycinate. The composition can further include at least one of oleic acid, oleanolic acid, ursolic acid, curcumin, piperine, galantamine, huperzine-A, a source of vitamin B5, L-tyrosine, and beta-hydroxybutyrate.

The invention discloses a phosphorylcholine cytidyltransferase mining method based on a deep learning model. According to the method, the limitation of traditional homologous comparison is broken through, and the CCT candidate enzyme which is high in catalytic activity, excellent in solubility and suitable for engineering application can be recognized in hundreds of millions of protein sequence spaces with higher screening efficiency and prediction precision. On the basis, a rational design and a zero sample mutation prediction strategy are combined to further obtain a CCT mutant with remarkably improved performance, so that a core catalytic element is provided for efficient biosynthesis of citicoline.

Novel citicoline derivatives are disclosed, including ddh-citicoline, comprising a choline moiety, attached to an organic functional group linking the nucleoside to the choline moiety, including prodrug modifications, wherein choline-conjugated pharmacophores / cargo could be delivered through the gut via promiscuous choline transporters. The invention further provides a nutraceutical or pharmaceutical composition comprising an inventive compound, and a pharmaceutically-acceptable excipient, preferably in a pharmaceutically-acceptable unit dosage.

The invention provides a therapeutic agent for Alzheimer's disease and application thereof, and belongs to the technical field of neurobiology. Each 100 [mu] L of the medicament comprises the following active ingredients: 0.25 mg to 0.35 mg of epigallocatechin gallate, 1.8 mg to 2.0 mg of citicoline and 0.2 mg to 0.35 mg of pterostilbene, and the balance of water. The medicament has positive influence on patients with Alzheimer's disease by regulating and controlling Abeta42 deposition, improving exploration ability and relieving anxiety mood. Therefore, the medicament has a wide clinical prospect in application, and a novel and synergistic treatment strategy can be provided for treating the Alzheimer disease.

The present application belongs to the technical field of bioengineering, and particularly relates to an engineered bacterium for producing cytidine diphosphate choline as well as a construction method and application thereof. The present application takes Bacillus subtilis BSC1-4 as a starting bacterium, blocks the conversion of choline to glycine betaine to reduce unnecessary loss of substrates in the fermentation process, improves the absorption of choline, and enables the substrates to continuously generate cytidine diphosphate choline in the direction of generating cytidine diphosphate choline. The construction method of the engineered bacterium is specifically as follows: the key genes of the choline degradation pathway in the genome of Bacillus subtilis are knocked out gbsA and gbsB , the transporter protein OpuD is overexpressed, and finally the transcriptional repressor genes opcR and gbsR are knocked out. Experimental results show that the engineered bacterium constructed in the present application has a cytidine diphosphate choline yield of 1181.6±11.5 mg / L after 24 h of fermentation in a shake flask.

The invention belongs to the technical field of bioengineering, and particularly relates to a recombinant engineering bacterium, a preparation method and application of the recombinant engineering bacterium in efficient production of citicoline. According to the invention, a plurality of aspects such as choline metabolic pathway of bacillus subtilis, enhancement of CTP precursor supply, reconstruction of central carbon metabolism and the like are modified, the finally constructed engineering bacterium is fermented for 24 hours in a shake flask, and the yield of citicoline reaches 1640.2 + / -2.4 mg / L; and fed-batch fermentation is carried out in a 5 L fermentation tank, the highest yield reaches 4788.4 + / -239.1 mg / L (149.0 + / -5.8 mg / g DCW) within 32 hours, and about 93% of products are accumulated in cells. The bacillus subtilis engineering bacterium constructed through modular engineering does not secrete endotoxin and is high in safety; only a cheap substrate choline chloride needs to be added for fermentation, and expensive cytidine monophosphate does not need to be exogenously added, so that the method has a remarkable cost advantage; meanwhile, high-proportion intracellular accumulation of the product is beneficial to separation and purification of subsequent products, and the method has huge industrial application potential.

The invention belongs to the technical field of analytical chemistry, and particularly relates to a quantitative detection method for citicoline concentration in blood. According to the method, a blood sample is pretreated by adopting a protein precipitation method, and the concentration of citicoline in the sample is analyzed and measured by taking an electrospray ionization source as an ionization technology and adopting a high performance liquid chromatography-tandem mass spectrometry method in a multi-reaction monitoring mode. According to the quantitative detection method for the citicoline concentration in the blood, the citicoline concentration in the blood can be effectively quantified, and the method is easy to operate, stable, reliable and high in detection sensitivity.

The present disclosure relates to the medical use of citicoline analogs with a N4-hydroxycytidine moiety and a solvate or pharmaceutically acceptable salt thereof. The compounds can be used as antiviral drug for treatment of e.g. Covid-19, human rhinovirus (HRV), influenza and respiratory syncytial virus (RSV).