79 results about "Pyrrovinyquinium" patented technology

The present invention relates to a biosensor which comprises an electrode system including at least one pair of electrodes, at least one insulating base plate for supporting the electrode system, a first reaction layer provided at least on a working electrode of the electrode system, including an organic compound having a functional group capable of bonding or being adsorbed to an electrode and a hydrophobic hydrocarbon group, a second reaction layer provided on the first reaction layer, including an amphiphilic lipid capable of bonding or being adsorbed to a hydrophobic portion of the first reaction layer, and a reagent system carried in a two-component membrane composed of the first and second reaction layers, including at least membrane-binding type pyrroquinoline quinone-dependent glucose dehydrogenase and an electron mediator.

The invention discloses a Hyphomicrobium sp. strain and a preparation method for pyrroloquinoline quinone. The Hyphomicrobium sp. strain 1112-NTG-2318 capable of realizing high yield of pyrroloquinoline quinine is preserved in China General Microbiological Culture Collection Center with an accession number of CGMCC No. 10709. The preparation method for pyrroloquinoline quinine comprises the following steps: fermenting the Hyphomicrobium sp. strain CGMCC No. 10709 in a fermentation medium and acquiring pyrroloquinoline quinine from fermentation broth. The fermentation titer of the preparation method in a tank with a volume of 80 m<3> reaches 1783 mg / L, so the preparation method is favorable for industrial production of pyrroloquinoline quinine.

The invention discloses a separation and purification method of pyrroloquinoline quinone in methylotrophic bacteria fermentation liquor and application of the method. The method comprises the following steps that firstly, the fermentation liquor is enriched through macroporous resin and then sequentially passes through a buffer solution and water for elution, eluate is collected, and enrichment liquid rich in pyrroloquinoline quinone is obtained; secondly, the enrichment liquid rich in pyrroloquinoline quinone is purified through hydrophilic silica gel filler, and pyrroloquinoline quinone mother liquid is obtained; thirdly, pyrroloquinoline quinone in the pyrroloquinoline quinone mother liquid is crystallized and separated out, and crude pyrroloquinoline quinone crystals are obtained; fourthly, the crude pyrroloquinoline quinone crystals are subjected to recrystallization by using the alkali-solution and acid-isolation method, and pyrroloquinoline quinone is obtained. The experiments prove that the method has the advantages of being simple in technological operation, high in connection degree and high in product recovery rate and purity, and the method can be used for large scale industrialized production preparation of pyrroloquinoline quinone.

The present disclosure relates to compounds of Formula (I) and process of obtaining the same. Said compounds of Formula (I) is employed in the syntheses of pyrroloquinoline quinone (PQQ), 4,5-dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid 2-allyl ester, 5-ethoxy-5-hydroxy-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid, 5-hydroxy-6-(1,1,4-trioxo-1 lambda*6*-1,2,5-thiadiazolidin-2-yl)-1H-indole-2-carboxylic acid and its pharmaceutically acceptable salts. Said syntheses of compounds via compounds of Formula (I) as intermediates employ minimum number of steps resulting in a shorter process and has improved efficiency along with many other advantages.

The invention discloses a method for separating and purifying pyrroloquinoline quinone disodium salt based on a fermentation raw material liquid. The method comprises: (1) primary filtration, (2) secondary filtration, (3) extraction of pyrroloquinoline quinone, (4) primary salting-out, (5) decolorization with activated carbon, (6) secondary salting-out, and (7) crystallization. The method has simple processes, realizes a low cost, can effectively shorten the product purification cycle, has a high product recovery rate and realizes the product purity of 99.5%.

The invention discloses a method for producing a 2-keto-L-gulonic acid (2-KLG) vitamin C precursor by modifying Escherichia coli and belongs to the field of genetic engineering. In the method, a sorbitol dehydrogenase (SLDH) gene from gluconobacter oxydans, a pyrroloquinoline quinine (PQQ) gene cluster and a sorbose dehydrogenase (SDH) / sorbosone dehydrogenase gene (SNDH) from common ketogulonigenium vulgare are expressed in Escherichia coli by a genetic engineering technique to culture an Escherichia coli engineering strain for producing 2-KLG by sorbitol. At present, a two-step fermentationprocess adopted for industrial production of vitamin C in China has the problems of complicated process, many influencing factors, difficult accurate control and large raw material and energy consumption for growing three kinds of microbes at the same time. When the production of the 2-KLG by sorbitol fermentation by the E.coli engineering bacteria is adopted, the production process is simplified, raw materials and energy are saved, and the yield of the 2-KLG can reach 87g / L; and thus, the method has a very bright application prospect.

The invention discloses a method for increasing the pyrroloquinoline quinone yield, belonging to the field of biotechnology. In the invention, according to analysis of trophic factors light green yellow pseudomonas produced pyrroloquinoline quinone, the yield of pyrroloquinoline quinone can be effectively increased by controlling the content of specific amino acid and vitamin content in a medium. By adopting the method disclosed by the invention, the pyrroloquinoline quinone yield of a strain can be increased by 15-89%. Moreover, the method disclosed by the invention is simple and easy to control and applicable to industrial application.

The invention relates to pyrroloquinoline quinine, derivatives and / or salts thereof and application to preparation of medicines for treating and / or preventing primary sicca syndrome, secondary sicca syndrome and mouth dryness, eye dryness and damage of multiple systems caused by fatigue of other exocrine glands and other organs outside glands thereof as well as a medicine composition of PQQ or PQQ combined active vitamins d, NAC, resveratrol, epigallocatechin gallate, curcumin, anthocyanin, vitamin E, vitamin C or vitamin D and the like. The medicine and the medicine composition can be used for treating sicca syndrome and adaptation diseases related to the sicca syndrome. The medicine and the medicine composition are capable of removing excess oxygen radicals in the body, inhibiting NF-kB activation caused by oxidative stress and inhibiting autoimmunity so as to reduce the inflammatory response of the sicca syndrome.

The invention discloses a functional biological compound fertilizer and a preparation method thereof. The functional biological compound fertilizer is prepared from the following raw materials: pyrroloquinoline quinine, an aphanamixis plant extract, a microbial agent, medium elements, namely nitrogen, phosphorus and potassium, and trace elements, namely calcium, magnesium, sulfur, zinc, boron and molybdenum. The aphanamixis plant branch and leave extract is prepared by the steps of soaking fresh branches and leaves of aphanamixis plants, then sterilizing, cleaning, chopping, grinding into thick liquid, juicing, concentrating, carrying out vacuum drying, granulating and the like. The extract is rich in various amino acids, high-quality plant protein, multiple organic trace elements, multiple active enzymes, superoxide dismutase (SOD) and multiple chelates, thus being capable of carrying out effective, multi-mechanism and complementary cooperation with the pyrroloquinoline quinine, and promoting the absorption of plants. Furthermore, the soluble fibers in the plant extract have a curing action with the pyrroloquinoline quinine, so that effective components are further dispersed, and the long-acting effect of the fertilizer is further improved.

The invention provides a purification method of pyrroloquinoline quinone. The method comprises the following steps: pretreating a fermentation liquid containing pyrroloquinoline quinone to obtain a filtrate; passing the obtained filtrate through a polyamide resin, then performing rinsing with an acidic aqueous solution, and discarding a leakage liquid; performing desorption with a mixed aqueous solution of an acid and a salt, and collecting a desorption liquid with a chromatographic purity of 90% or more; adjusting pH of the desorption liquid, first performing ultrafiltration, and then performing nanofiltration and concentration; and finally performing crystallization and drying. The method uses the polyamide resin to separate the pyrroloquinoline quinone fermentation liquid, and then thepyrroloquinoline quinone crystal with HPLC purity >= 98% and content >= 96% can be obtained by combination with crystallization. The used polyamide resin is cheap and easy to obtain, the purificationprocess is simple, and the cost is effectively reduced. In addition, resin regeneration of the polyamide resin used in the invention can be completed with lye, and an organic solvent used in the entire process is greatly reduced, so that the wastewater COD is greatly reduced, and the explosion-proof requirement of plant facilities is also reduced.

A method for extracting pyrroloquinoline quinone from fermentation broth mainly comprises the following steps: pretreating the fermentation broth to obtain a filtrate, adjusting the pH value of the filtrate to 2.5-3.5 with an acid, adding an adsorbent, and carrying out first filtration to obtain a filtrate; adjusting the pH value of the filtrate to 7.5-8, adding an adsorbent, and performing filtering for the second time to obtain a filtrate; and carrying out ultrafiltration and nanofiltration on the filtrate to obtain a nanofiltration concentrated solution, carrying out reduced pressure concentration on the nanofiltration concentrated solution, adjusting the pH value to 3-3.5, and carrying out low-temperature crystallization to obtain the product. The purity of the final product PQQ is greater than or equal to 98%, the total yield is greater than or equal to 85%, and multistage membrane equipment is adopted in the extraction process, so that the extraction operation is simpler, the automatic operation is easier, the equipment maintenance cost is reduced, the use amount of organic solvents in production is reduced, and the production cost of enterprises is reduced.

The invention provides an immunomodulator for relieving animal cell and intestinal inflammatory responses induced by lipopolysaccharide (LPS) and application of the immunomodulator. The immunomodulator is pyrroloquinoline quinone (PQQ). PQQ is applied to relieving inflammatory injury of LPS-induced macrophages and animal bodies for the first time. The invention also provides a preparation method of a feed additive for relieving animal cell and intestinal inflammatory injury and application of the feed additive in animal production. PQQ serves as the immunomodulatory type feed additive, and caneffectively relieve the animal cell and intestinal inflammatory injury induced by harmful microorganisms and improve the antioxidant function of organisms. By propelling the application of the immunomodulatory type feed additive in livestock production is beneficial to improving the immune function and antioxidant function of the animal bodies, reducing the occurrence of epidemic diseases and improving economic benefits of livestock and poultry farmers.

The invention discloses an application of pyrroloquinoline quinone to medicines resistant to asthma and allergic reaction. Pyrroloquinoline quinone can relieve allergic airway inflammation through antioxidant and anti-inflammatory effects, and is a potential novel medicine for the treating asthma. Pyrroloquinoline quinone has high antioxidant and anti-inflammatory effects. The in-vivo and in-vitrostudies carried out by the invention show that pyrroloquinoline quinone can reduce allergic airway inflammation by improving the immune microenvironment and regulating a JAK-STAT signaling pathway, and research shows that pyrroloquinoline quinone is safe for oral administration, so that pyrroloquinoline quinone is a potential novel medicine for treating asthma. Pyrroloquinoline quinone exists naturally in nature and can be supplemented by diet, the safety is good, the side effects are low, and the accessibility is high. Pyrroloquinoline quinone is a non-glucocorticoid immunomodulator that targets an asthma inflammatory pathway, the mechanism of medicine action is different from that of current medicines for treating asthma, and mutual complementing can be carried out.

The invention discloses a preparation method for synthesizing pyrroloquinoline quinone by a four-step method. According to the method, 4-methyl-5-nitro-2-fluoroaniline (2) is taken as a raw material,and is subjected to a ring closing reaction twice to obtain a key intermediate 5-methoxy-1H-pyrrole [2,3-f] quinoline-2,7,9-trialkyl triformate (6), and an oxidation reaction, a hydrolysis reaction and an acidification reaction are performed to obtain the pyrroloquinoline quinone (PQQ, 1). The preparation method disclosed by the invention has the advantages of environmental friendliness, easily available raw materials, low cost, simple method and suitability for industrial production, and solves the problems of high preparation cost and difficulty in industrial production in the prior art.

The invention discloses methylophilus pyrroloquinoline quinine synthesis gene clusters and encoding protein systems thereof, wherein the gene clusters are pqqABCDE and pqqFG, respectively. The invention also discloses encoded pyrroloquinoline quinine synthesis gene clusters, and the nucleotide sequences are shown in SEQ ID No.1 and SEQ ID No.12. The gene clusters provided by the invention can promote the synthetic quantity of methylophilus pyrroloquinoline quinine, and the introduction of both the two gene clusters has synergistic interaction for the promotion of the synthesis of pyrroloquinoline quinine.

The invention provides a pyrroloquinoline quinone separation and purification method, which comprises: (1) pretreatment: removing proteins from a filtrate obtained by filtering a pyrroloquinoline quinone-containing fermentation broth under an acidic condition, and carrying out ultrafiltration and nanofiltration concentration to obtain a pyrroloquinoline quinone concentrated solution; (2) extraction-back extraction: adding oxalic acid to the concentrated solution, controlling the pH value of the system to be 2.0-3.0, extracting with an organic solvent to obtain an extraction solution, and carrying out back extraction on the extraction solution by using a buffer solution with the pH value of 2.0 to 3.0 to obtain a back extraction solution, wherein the ratio of the addition amount of oxalicacid to the mass volume of the concentrated solution is (0.1-1 g):100 mL; and (3) crystallization-decolorization-recrystallization: crystallizing the back extraction solution to obtain a crude crystal, and carrying out decoloration treatment and recrystallization on the crude crystal to obtain a pyrroloquinoline quinone product. The method can be used for efficiently extracting pyrroloquinoline quinone and has the advantages of simple process, low cost and the like.

The invention provides a method for eliminating a side product polysaccharide in fermentation production of pyrroloquinoline quinone. According to the method, in microorganism fermentation production of pyrroloquinoline quinone, a gene knockout method is used for knockout of an important gene in a polysaccharide synthetic gene cluster of a pyrroloquinoline quinone production strain so that the production strain loses the capability of exopolysaccharide synthesis without reducing the capability of producing pyrroloquinoline quinone. According to the method disclosed by the invention, the important gene mpq_1844 in the polysaccharide synthetic gene cluster of the PQQ (pyrroloquinoline quinone) production strain Methylovorussp.MP688 is successfully knocked out by a double-exchange homologous recombination method, the gene knockout strain of the original production strain no longer synthesizes exopolysaccharide, thus the metabolism side product polysaccharide generated in microorganism fermentation production of the pyrroloquinoline quinone is eliminated, the aim of simplifying the purification technique is achieved and the foundation is laid for industrial and efficient preparation of pyrroloquinoline quinone.

The invention relates to skin liniment. The skin liniment comprises: 5-15% by weight of wormwood essential oil; 20-50% by weight of phospholipid, preferably lecithin, more preferably hydrogenated lecithin; and 30-60% by weight of an aqueous solution of pyrroloquinoline quinone, preferably a concentration of 0.05-0.5%, more preferably a concentration of 0.1-0.15%. The present invention also relatesto compositions of the liniment containing the mixture. The composition can delay the process that the wormwood essential oil is absorbed and enters the skin after being used, enhances the ability that the pyrroloquinoline quinone penetrates into the skin, and plays a role in exerting the comprehensive protection effect of the three basic substances on the skin and the human body.

A new composition including substances that prolong and enhance the quality of the female reproductive system; effectively reducing the physiological effects of aging of the female reproductive system. In some aspects, the composition of the present invention includes coenzyme Q10, vitamin C, and vitamin E. As well, in some aspects, the composition of the present invention includes coenzyme Q10, resveratrol and pyrroloquinoline quinone (PQQ). In another aspect, the composition of the present invention further comprises vitamin D. In another aspect, the composition of the present invention comprises folic acid. In some aspects, the composition of the present invention increases the rate of fertility in women and promotes the development of the fetal nervous system.

The invention discloses a method for producing pyrroloquinoline quinone by regulation and control of methylotrophic bacteria through redox potential. The method comprises the steps of strain activation, seed culture and fermentation production. A redox potential electrode is introduced into a system for producing the pyrroloquinoline quinine through fermentation of the methylotrophic bacteria, and the change of the redox potential in a high-potential oxidation stage and a low-potential reduction stage in a fermentation production stage is adjusted by controlling a ventilation capacity and a stirring speed in the system, and therefore, growth of bacteria and accumulation of the pyrroloquinoline quinine are ensured. According to the method, fermentation time can be shortened, and meanwhile, the yield and the productive rate of the pyrroloquinoline quinone and the stability of a fermentation system are improved.

The invention discloses a method for producing pyrroloquinoline quinone by utilizing Gluconobacter oxydans. The steps are as follows: (1) Fermenting Gluconobacter oxydans DSM 2003 to obtain a fermentation liquid; (2) High-speed centrifugation of the fermentation liquid to obtain the supernatant Liquid, enriched by HP‑20 type macroporous resin chromatographic column to obtain the elution fraction rich in pyrroloquinoline quinone; (3) concentrating the elution fraction rich in pyrroloquinoline quinone under reduced pressure, Purified by amide column chromatography to obtain pure pyrroloquinoline quinone. The Gluconobacter oxidans strain provided by the present invention has a PQQ output of 125 mg / L under conventional culture medium and culture conditions, and the above-mentioned production and preparation method has simple conditions, quick process, and is convenient for large-scale industrial production, which is helpful for promoting the industrialization of PQQ have important meaning.

The invention discloses a formula of a cannabidiol soft-jelly candy and a preparation process and relates to the technical field of production of soft candies. The formula is used for solving the problem that benefited people are limited. The formula of the cannabidiol soft-jelly candy comprises the following ingredients in parts by weight: 15 parts of cannabidiol and 15 parts of pyrroloquinolinequinone. The preparation process for the cannabidiol soft-jelly candy comprises the following steps: weighing all the ingredient raw materials in parts by weight, and furthermore, traying, baking andcooling starch for later use. According to the formula of the cannabidiol soft-jelly candy and the preparation process, the soft candy is rich in nutrient elements such as the cannabidiol, the pyrroloquinoline quinone and collagen peptides, can serve as snacks, can be used for effectively preventing and treating Alzheimer's disease, improving memory, stimulating growth of human cells, improving cell density and improving metabolic capability and growth functions of organism tissue and can be used for effectively clearing away in-vivo free radicals, reducing injuries to human bodies caused by the free radicals, protecting the organism tissue, promoting amino acid absorption and conditioning various nervous system diseases.

The invention discloses an application of pyrroloquinoline quinone (PQQ) in prevention and / or treatment of female reproductive dysfunction. Research results of the invention show that supplement of pyrroloquinoline quinone can significantly improve follicle quantity and quality and reduce fertility of model mice. According to the invention, pyrroloquinoline quinone is used for treating reproductive function reduction caused by quantity reduction or quality reduction of follicles for the first time, a relatively ideal treatment effect is achieved, a new prevention and treatment choice is provided for clinical application and treatment of female reproductive dysfunction, and the pyrroloquinoline quinone has extremely high application value.

The intention discloses a preparation method for synthesizing pyrroloquinoline quinone by a five-step method, and the method comprises the following steps: by using 4-methyl-5-nitro-2-fluoroaniline (2) as a raw material, carrying out cyclization reaction twice to obtain a key intermediate 5-fluoro-1H-pyrrole [2, 3-f] quinoline-2, 7, 9-triformatetrialkyl ester (6); and carrying out hydrolysis reaction, substitution reaction and oxidation reaction to obtain pyrroloquinoline quinone (PQQ, 1). The preparation method has the advantages of greenness, environmental friendliness, easily available rawmaterial, low cost, simple method and suitability for industrial production, and solves the problems of high preparation cost and difficulty in industrial production in the prior art.

The invention belongs to the technical field of human health, and particularly discloses an edible compound recipe mitochondrial energy enhancing formula.The edible compound recipe mitochondrial energy enhancing formula comprises the components of pyrroloquinoline quinone, coenzyme Q10, nicotinamide mononucleotide, mecobalamin, calcium L-5-Methyltetrahydrofolate and complex vitamins B. The ediblecompound recipe mitochondrial energy enhancing formula is prepared through the steps of mixing the pyrroloquinoline quinone with the coenzyme Q10, the nicotinamide mononucleotide, the mecobalamin, thecalcium L-5-Methyltetrahydrofolate and the complex vitamins B to obtain finished products of the enhancing formula, and adding synergistic reaction components for NAD on-line plastochondria respiratory chain complexes and components for strengthening mitochondrial biogenesis, so that the respiratory chain metabolism efficiency is comprehensively improved, and the problem that a NAD precursor is separately supplemented, and the effect of improving vigour is not achieved, is solved. The components for assisting in NAM metabolism and discharge are added, so that the organism metabolism NAM pressure is reduced, and the potential risk that the NAD precursor is taken for a long time can be reduced.

The invention relates to a novel drug application of pyrroloquinoline quinine and derivatives and / or salts thereof. The novel drug application particularly relates to application of pyrroloquinoline quinine and derivatives and / or salts thereof in preparation of drugs for treating and / or preventing virus infection and complications such as pneumonia and inflammatory storm caused by virus infection. According to the invention, pyrroloquinoline quinone, derivatives and / or salts thereof are used for preparing medicines for treating and / or preventing virus infection and indications such as pneumonia, inflammatory storm and the like caused by the virus infection for the first time.

The invention relates to application of pyrroloquinoline quinone to the preparation of a product with fatigue resistance and oxidative stress injury alleviating. Experiments show that pyrroloquinolinequinone has obvious effects of anti-fatigue and prolonging exercise time, and down-regulates oxidative stress to varying degrees, reduces tissue damage caused by oxidative stress, reduces inflammatory reaction caused by oxidative stress, and maintains homergy of bodies; and in a long-term contraction myotube model, pyrroloquinoline quinone maintains normal mitochondrial morphology, stabilizes mitochondrial function, and inhibits the production of reactive oxygen free radicals (ROS, reactive oxygen species), thereby reducing the damage caused by oxidative stress and delaying the occurrence offatigue, and the effect is very good.

The invention belongs to the technical field of microorganisms, and particularly relates to a methylovous.sp HQ-1 with the preservation number of CCTCC (China Center For Type Culture Collection) NO: M2021252. The invention also relates to an application of the Methylovous.sp HQ-1 in fermentation production of the pyrroloquinoline quinone, a method for preparing the pyrroloquinoline quinone, and a composition thereof. The methylovous.sp HQ-1 provided by the invention is aerobically cultured for 1-2 days in a culture medium taking methanol as a carbon source and peptone as a nitrogen source, and the yield of pyrroloquinoline quinone can reach 100mg / L at a shake flask level. The strain screened by the invention can secrete PQQ out of cells, and compared with a common PQQ producing strain, the strain has the advantage of rapid growth, and a new strain is provided for industrial fermentation production of PQQ.