30 results about "Citicoline" patented technology

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.

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.

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 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 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.

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 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 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-acetylcarnitine and at least one vitamin of group B. 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.

A caffeine-free, ready-to-drink liquid composition is provided for pre-caffeine cognitive priming. A unit dose of about 2.0 to 3.0 ounces at pH about 3.0 to 3.5 comprises N-acetyl L-tyrosine, citicoline, phosphatidylserine, one or more adaptogenic botanicals, L-citrulline, piperine, vitamins B6 and B12, a magnesium source, and an acidulant system including malic acid with limited citric acid. A sensory agent, such as ginger CO2 extract, yields perceivable warming or tingling within minutes, with palate clearance in about sixty seconds. Methods include administering the composition about 2 to 45 minutes before consuming a caffeinated beverage to provide rapid, predictable onset while maintaining beverage flavor compatibility. Packaged systems may use nitrogen-flushed PET or glass, cold-fill, and high-pressure processing or low-temperature pasteurization, with optional low-level carbonation and microencapsulation to manage bitterness, dissolution, and stability.

The present invention discloses a recombinant engineering bacterium of Escherichia coli for producing citicoline and a construction method and application thereof, belonging to the field of biotechnology; Escherichia coli K‑12 MG1655-based knockout of the genomic cytidine deaminase gene cdd The temperature-controlled expression vector PBV220 was used to express SpnCCT‑SpnCKI‑pRpLpyrG Mutating the gene cluster enhances the expression of the choline transporter BetT and disrupts Escherichia coli ptsH‑ptsI‑ crr locus, and simultaneously introduced from Zymomonas mobilis ( Zymomonas mobilis ) glucose permease gene glf and glucokinase genes glk , and obtained the recombinant Escherichia coli ZMCB02NCL capable of efficiently biosynthesizing citicoline, with the deposit number being CCTCC NO: M 2025483.

Provided herein are methods and compositions comprising effective amount of lutein, zeaxanthin, and citicoline for Eye Health, Mental Focus, and Memory Support, wherein the effective amount of citicoline synergistically effects lutein and zeaxanthin immediately and over time, and the composition is to be ingested as a Nutritional Supplement Blend, Dietary Supplement, Functional Food or Functional Beverage.

This invention provides a genetically engineered strain for the fermentation production of cytidine diphosphate choline (CMP) and its applications. The invention discloses an optimized genetically engineered strain for CMP production, its construction method, and a method for production using the strain. In this invention, Cct, Cki, Hnm1, and sATP6 proteins are overexpressed in engineered yeast strains using gene recombination technology. More preferably, the expression or activity of His4, Ku70, Shble, 5'-NT, and / or Cda proteins is downregulated to obtain an engineered yeast strain capable of producing CMP. The engineered yeast strain of this invention has characteristics such as low metabolic background, strong heterologous expression ability, and the ability to utilize phosphocholine and CMP as substrates, achieving high-level fermentation production of CMP with high substrate conversion rates, providing a new approach for the industrial production of CMP. This invention also optimizes the fermentation production system using the engineered strain, providing a fermentation method for high-yield CMP production.

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-acetylcarnitine 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 application relates to a kind of preparation, separation detection method and application of the impurity of sodium cytidine phosphate with structure I, comprising the following steps: 5'-cytidylic acid, choline phosphate and sodium tert-butanolate aqueous solution are mixed to be prepared into reaction solution, then catalyst is added to carry out reaction, the solution after reaction is collected, chromatographic column chromatography separation, crystallization drying, the impurity of sodium cytidine phosphate with structure I is obtained.The raw material of the preparation method of the present application is environmental protection, process is simple, yield is high, fills the technical blank of the preparation of the impurity of sodium cytidine phosphate with structure I, and the research on the preparation method is conducive to guiding the optimization of cytidine phosphate sodium synthesis process route and ensuring cytidine phosphate sodium safe drug use.

The invention belongs to the technical field of gene engineering, and particularly relates to engineering modified bacillus subtilis, a preparation method and application thereof. In the invention, in order to improve the supply of precursor cytidine triphosphate (CTP) in the process of producing citicoline by fermentation of bacillus subtilis, firstly, CTP synthetase PyrGE156K with feedback inhibition removed is overexpressed, and the conversion from uridine triphosphate to CTP is promoted; then, a repressor protein gene pyrR of the pyrimidine operon is knocked out, synthesis of uridine monophosphate is promoted, and then synthesis of CTP is promoted; finally, the pyrimidine nucleotide degradation genes pdp and cdd are knocked out, conversion from uridine / cytidine to uracil / cytosine and conversion from cytidine to uridine are blocked respectively, consumption of pyrimidine nucleotide is reduced, and intracellular accumulation of CTP is facilitated. The citicoline yield of the finally constructed engineering bacterium is about 12.6 times of the yield of the original starting bacterium, and the result of the invention further proves the importance of CTP on citicoline synthesis.

The application provides a preparation method of a sodium citicoline injection, and belongs to the technical field of preparations. The preparation method is as follows: dissolving sodium citicoline pure product in water, filtering, sequentially filtering through a redundant sterilization filter and a main sterilization filter, filling and sealing, placing the obtained liquid medicine after filling and sealing in a sterilization device preheated to 100 DEG C, sterilizing at 121 DEG C for 10 min, reducing the temperature to below 40 DEG C, and then detecting leakage, so that the sodium citicoline injection is obtained. The impurity E in the prepared sodium citicoline injection is successfully controlled below 0.5%, and the drug safety of the sodium citicoline injection is improved.

The utility model discloses a dilution device for citicoline sodium injection, which comprises a support frame, a station plate is fixed on the top surface of the support frame, two groups of dilution buckets are arranged at the working position of the station plate, the dilution buckets and the station plate are obliquely arranged from top to bottom, mixing parts are arranged on the inner wall of the dilution buckets in a circumferential array, and the mixing parts are arranged on the inner wall of the dilution buckets. An arc-shaped filtering plate is arranged at the bottom of the diluting barrel, a discharging head is connected to the surface of the diluting barrel, a sampling pipe is connected to the back face of the diluting barrel, an extending base is welded to the back face of the supporting frame, and a PH detecting pen is connected to the top end of the extending base. According to the citicoline sodium injection diluting device, the efficiency, safety and precision of citicoline sodium injection diluting are remarkably improved, liquid medicine is efficiently mixed in an inclined state, splashing is avoided, double barrels of liquid medicine can be synchronously filtered through accurate butt joint of the arc-shaped filter plate and the discharging head, the process switching time is shortened, and the whole process automation of sampling, calibration and detection is achieved through the integrated PH detection design.

The application relates to a preparation method of a medicine composition for treating diabetic peripheral neuropathy, in particular to the following steps: mixing sodium citicoline, a binder, a filling agent, a disintegrating agent and a lubricant to obtain sodium citicoline mixed powder; mixing methylcobalamin, a binder, a filling agent, a disintegrating agent and a lubricant to obtain methylcobalamin mixed powder; compressing the sodium citicoline mixed powder and the methylcobalamin mixed powder on a double-layer tablet press to obtain double-layer double-release tablets; and coating the double-layer double-release tablets with light-shielding coating agent. The medicine composition for treating diabetic peripheral neuropathy prepared by the application is prepared into double-layer tablets by using sodium citicoline and methylcobalamin, which effectively guarantees the content uniformity of the medicinal components, the distribution uniformity in the tablets and the medicinal stability, reduces the medicine taking frequency and the auxiliary material intake amount of patients, and improves the use compliance of the patients.

The invention discloses a method for separating and purifying citicoline, which comprises the following steps: (1) carrying out enzyme inactivation, microfiltration, nanofiltration and electrodialysis pretreatment on citicoline conversion liquid to obtain pretreatment liquid; (2) adjusting the pH value of the pretreatment solution to 2.0-14.0, loading a sample to anion resin for adsorption, washing impurities with pure water, eluting with an inorganic salt aqueous solution, and collecting an eluent; and carrying out nanofiltration, desalination, concentration and crystallization on the eluent obtained in the step (2) to obtain pure citicoline. The separation process is simple, and the separation cost is low; loss caused by multiple separation operations is avoided in the whole treatment process; and the product is easy to crystallize, and the citicoline product with high purity and high yield can be obtained.