74 results about "Aldose reductase" patented technology

The present invention relates to a novel Saccharomyces cerevisiae strain utilizing xylose for fermenting ethanol expressing xylose isomerase (XI), overexpressing xylulokinase (XK), overexpressing the pentose phosphate pathway (PPP), and non-expressing aldose reductase (AR) and being adapted to growth in mineral defined medium with xylose as sole carbon source.

A method for treating diabetic complications by administration of a beta-blocker is disclosed. Diabetic complications arise from diabetes and have few or no existing treatment options. The present invention describes the use of a beta-blocker in the treatment of a diabetic. The present invention also describes the inhibition of aldose reductase, one of the chief causative factors of diabetic complications. Also provided are methods of diabetic wound healing. Compositions for treating diabetic complications, such as diabetic wounds, are disclosed. The present invention includes employing a topical formulation of a beta-blocker, having substantially no antibacterial activity, to improve the process of diabetic wound healing. The present invention also involves increasing the rate of collagen accumulation of the healing epithelialized tissue in the wound of a diabetic individual.

Provided herein is a crystallized ternary structure of aldose reductase (AR) bound to NADPH and γ-glutamyl-S-(1,2-dicarboxyethyl)cysteinylglycine (DCEG). Also provided are specific inhibitors of glutathione-aldehyde binding to aldose reductase which are designed via at least computer modeling of the ternary AR:NADPH:DCEG structure and methods of designing and of screening the inhibitors for inhibition of glutathione-aldehyde binding to aldose reductase.

The invention relates to a novel choline cocrystal of 5-[(lZ.2E)-2-methyl-3-phenylpropenylidene]-4-oxo-2-thioxo-3-thiazolidineacetic acid. The preparation and characterization of the novel choline cocrystal according to various embodiments of the invention is described. The invention also relates to pharmaceutical compositions containing the novel choline cocrystal and the therapeutic use of the novel choline cocrystal to treat and / or prevent various conditions, including treating and / or preventing diabetic complications, treating and / or preventing homocystinuria reducing levels of homocysteine in blood serum, inhibiting aldose reductase, and affording cardioprotection in non-diabetic patients.

The present invention relates to a preventive and / or therapeutic agent for spinal canal stenosis comprising aldose reductase inhibitory compounds. A representative example of aldose reductase inhibitory compounds is the compound represented by formula (I): wherein all the symbols represent the same meaning as described in the specification; a salt of its acid when R3a represents hydrogen, or solvate thereof The therapeutic agent of the present invention is effective for prevention and / or therapy for spinal canal stenosis and the like, such as lumbar spinal canal stenosis.

The invention discloses a method for preparing a nebivolol hydrochloride epoxy intermediate 6-fluoro-2-epoxy ethyl chroman. The method includes the following steps that firstly, under the conditions that water, phosphate, inorganic alkali B1, zinc chloride, a hydrogen source, aldose reductase and NADPH exist, the temperature is 30-70 DEG C and the pH value is 6.0-8.0, a reduction reaction happens to 2-chloro-1-(6-fluorochromane-2-yl)-ethanon, and 2-chloro-1-(6-fluorochromane-2-yl)-alcohol is obtained; secondly, 2-chloro-1-(6-fluorochromane-2-yl)-alcohol is heated in a C1-C6 alkanol solvent and inorganic alkali B2 for a reflux reaction, an organic ester solvent is added dropwise for crystallization after the reaction ends, and 6-fluoro-2-epoxy ethyl chroman is obtained. The preparation method is mild in reaction condition, raw materials and solvents are easy to obtain, and the method is suitable for industrial production.

The invention provides a recombined saccharomyces cerevisiae strain for producing ethyl alcohol, a construction method of the recombined saccharomyces cerevisiae strain and a method for producing ethyl alcohol through the recombined saccharomyces cerevisiae strain. According to the recombined saccharomyces cerevisiae strain for producing ethyl alcohol, a wild type saccharomyces cerevisiae strain is used as an original strain, an XI xylose metabolism pathway is introduced into the original strain, the expression of four key genes in a PPP pathway is enhanced, meanwhile, the aldose reductase gene GRE3 is knocked out, the nitrobenzene phosphatase gene PHO13 is optionally knocked out, and XI protein and XK protein introduced exogenously are positioned to a yeast cell membrane through the membrane positioning effect of a membrane positioning group. The recombined saccharomyces cerevisiae strain for producing ethyl alcohol can efficiently carry out xylose metabolism, so that co-fermentation of C5 sugar and C6 sugar is achieved, and therefore the higher ethyl alcohol conversion rate is achieved.

Provided herein is a crystallized ternary structure of human aldose reductase (AR) bound to NADPH and γ-glutamyl-S-(1,2-dicarboxyethyl)cysteinylglycine (DCEG). Also provided are specific inhibitors of glutathione-aldehyde binding to aldose reductase which are designed via at least computer modeling of the ternary AR:NADPH:DCEG structure and methods of designing and of screening the inhibitors for inhibition of glutathione-aldehyde binding to aldose reductase.

The invention discloses Ganoderma triterpene and a pharmaceutical composition and application thereof. The Ganoderma triterpene has a chemical formula shown in general formula (I) that is shown in the description. The Ganoderma triterpene is active to inhibit aldose reductase and has a promising application prospect.

A medical application of general cactus flavone in preparing the natural medicine or health-care food acting to suppress aldose reductase for preventing and treating the complication of diabetes suchas the healing defect of corneal injury, cataract, neuropathy, retinopathy and renal disfunction. The said general cactus flavone is prepared by the solvent extraction method or resin adsorption method and conventional drying method.

The invention relates to the use of human bendazac lysine in pharmaceutical industry, wherein the bendazac lysine possesses substantial actions for reducing hypoglycemia and saccharifying hemoglobin and urine protein, thus can be applied to the prevention and treatment of diabetes.

The invention relates to an azepine brazilin compound and a synthesis method thereof. By using the structure of a natural product brazilin as a simulation object, a series of brazilin structure compounds containing nitrogen atoms are designed; and substituted cinnamic acid is used as a raw material, and a series of azepine brazilin compounds is obtained through serial chemical conversion and synthesis. Partial azepine brazilin compounds have strong anti-cancer activity, partial compounds have anti-HIV (Human Immunodeficiency Virus) activity, and partial compounds have aldose reductase suppressive activity and obviously reduce the blood sugar level. Medical compositions prepared from the compounds and at least one pharmaceutically acceptable excipient or carrier can be used for treating cancer and resist virus infections.

Provided herein is a crystallized ternary structure of aldose reductase (AR) bound to NADPH and γ-glutamyl-S-(1,2-dicarboxyethyl)cysteinylglycine (DCEG). Also provided are specific inhibitors of glutathione-aldehyde binding to aldose reductase which are designed via at least computer modeling of the ternary AR:NADPH:DCEG structure and methods of designing and of screening the inhibitors for inhibition of glutathione-aldehyde binding to aldose reductase. In addition methods of treating a pathophysiological state or symptoms thereof resulting from aldose reductase-mediated signaling in a cytotoxic pathway using a small interfering RNA (siRNA) or the designed inhibitors.

The invention relates to the technical field of pharmaceutical chemistry, and especially relates to an apigenin-7-O-beta-D-glucuronide derivative, and a preparation method and application thereof. The provided apigenin-7-O-beta-D-glucuronide derivative has the structure shown as the formula I, and is relatively high in water solubility, and thus the characteristic that apigenin-7-O-beta-D-glucuronide is not easy to dissolve in water is changed. The provided preparation method comprises: taking apigenin-7-O-beta-D-glucuronide as a raw material, and using an inorganic-base or organic-base reaction to generate the provided apigenin-7-O-beta-D-glucuronide derivative. The preparation method is simple and easily practicable in technology. Experiments show that the provided apigenin-7-O-beta-D-glucuronide derivative has high inhibition rate on aldose reductase compared with apigenin-7-O-beta-D-glucuronide, and the apigenin-7-O-beta-D-glucuronide derivative prepared by employing the preparation method has the purity larger than 99% and the yield larger than 79%.

The invention discloses a meroterpenoid compound, a medical composite thereof and the application thereof. The compound has the structure shown as chemical formula (I). The compound has the activity on inhibiting aldose reductase and has a good application prospect.

To provide a protective agent for a retinal nerve or an optic nerve, which exhibits its efficacy through a mechanism that is different from that for a conventional therapeutic agent and can be ingested over a long period. [MEANS FOR SOLVING PROBLEMS] Disclosed is protective agent for a retinal nerve or an optic nerve, which comprises a compound having an inhibitory activity on an aldose reductase, such as a compound represented by the general formula below, as an active ingredient. Preferably, the compound is (2S,4S)-6- fluoro-2',5'-dioxospiro[chromane-4,4'-imidazolidine]-2- carboxamide. wherein X represents a halogen atom ora hydrogen atom; R and R independently represent a hydrogen atom or a C1-6 alkyl group which may be substituted, or R and R together with a nitrogen atom located at the base of R and R or additionally together with other nitrogen atom or an oxygen atom may form a 5- to 6-membered heterocyclic ring.

Disclosed herein are a leaf and stem extract of Aster koraiensis, a root extract of Aster koraiensis, a flower extract of Aster koraiensis, a pharmaceutical composition for the prevention or treatment of diabetic complications, a health functional food for the improvement of diabetic complications, and a pharmaceutical composition and health functional food for the prevention or delay of aging, in which each of the compositions and the foods contain, as an active ingredient, at least one of the Aster koraiensis extracts. Each of the extracts is obtained by drying and finely cutting each of the leaf and stem part, root and flower of Aster koraiensis, extracting the cut plant with alcohol or aqueous alcohol solution, filtering the extracted solution and concentrating the filtrate under reduced pressure. Also disclosed are a pharmaceutical composition for the prevention or treatment of diabetic complications, a health functional food for the improvement of diabetic complications, and a pharmaceutical composition and health functional food for the prevention or delay of aging, which contain, as an active ingredient, at least one of fractions obtained by fractionating each of the Aster koraiensis extracts in the order of hexane, ethyl acetate, n-butanol and water fractions. The leaf and stem extract of Aster koraiensis, the root extract of Aster koraiensis and the flower extract of Aster koraiensis have the effect of inhibiting the production of advanced glycation endproducts (AGEs), the causes of diabetic complications, and effectively inhibit aldose reductase (AR) activity. Thus, the disclosed extracts will be highly useful for the prevention or treatment of diabetic complications and the prevention of aging.

The invention belongs to the field of natural medicines and discloses a beta-sitosterol and epalrestat conjugate, a preparation method and application of the conjugate. The conjugate is formed by coupling beta-sitosterol with epalrestat. The structure is shown as formula (I) described in the specification. The preparation method comprises the following steps: dissolving beta-sitosterol and epalrestat in anhydrous dichloromethane, reacting under room temperature overnight under the catalytic effect of pyridine and 4-dimethylamino pyridine, filtering, pouring onto a silica gel chromatographic column, performing rotary steaming and drying, thereby acquiring a target compound. An in vitro MTT detection experiment proves that the beta-sitosterol and epalrestat conjugate has an excellent restraining effect on tumor cell lines, has an IC50 value being 3-6 times that of beta-sitosterol but has low toxicity to normal liver cells L-O2. The compound is used for treating tumor in the manner of conjugating two drug molecules into prodrug, the problems of insufficient antitumor capacity of beta-sitosterol and synergic targeted inhibition for cancer cell aldose reductase target are solved and the effect of clearing away tumor cells in the manner of enhancing cell apoptosis can be achieved.

Disclosed is a Chinese traditional medicine preparation for treating diabetic chronic retinopathy and preparation method, wherein the preparation comprises (by weight ratio) root of Chinese trichosannthes 15-30, euonymus 15-30, safflower 5-15, butterflybush flower 5-15, mulberry leaf 10-12, chrysanthemum flower 10-20. The raw material is disintegrated and made into medicinal powder.

The invention relates to a method and application of extracting naringenin from the Chinese traditional medicine, bamboo brier. The method includes pulverizing the Chinese traditional medicine bamboo brier, cold soaking in 70% ethanol to obtain the leach solution, concentrating to obtain the extract, suspending in distilled water, extracting and defatting with the petroleum ether, and extracting the defatted water phase with ethyl acetate; performing chromatography on the ethyl acetate phase in a silica gel column, eluting with ethyl acetate-methanol system (9:1), collecting the eluent part by part, combining and concentrating the frontmost segment, gradient eluting with chloroform: methanol with the silica gel column, collecting in a sectional manner, and concentrating to separate the precipitate; and repeatedly purifying with column, and re-crystallizing with methanol to obtain white needle crystal. In the method, pure 3(S)-5,7, 4'-trihydroxy flavanone, i.e., naringenin, extracted from the Chinese traditional medicine bamboo brier, has aldose reductase and Alpha-glucosidase inhibiting activity and is effective in adjusting and controlling glucose absorption of small intestine and preventing and treating diabetic complication. The purified monomer has clear structure and remarkable effect, which facilitates the quality control and the Chinese traditional medicine modernization process; and the naringenin can be further chemically modified to deeply study occurrence and development mechanism of diabetes and complication thereof so as to develop the new drug for treating diabetes and complication thereof.

The invention relates to a novel choline cocrystal of 5-[(1Z,2E)-2-methyl-3-phenylpropenylidene]-4-oxo-2-thioxo-3-thiazolidineacetic acid. The preparation and characterization of the novel choline cocrystal according to various embodiments of the invention is described. The invention also relates to pharmaceutical compositions containing the novel choline cocrystal and the therapeutic use of the novel choline cocrystal to treat and / or prevent various conditions, including treating and / or preventing diabetic complications, treating and / or preventing homocystinuria reducing levels of homocysteine in blood serum, inhibiting aldose reductase, and affording cardioprotection in non-diabetic patients.

Embodiments of the invention include methods and compositions for the inhibition of Aldose Reductase by nitric oxide. Certain embodiments of the invention include the induction of nitric oxide by administration of a nitric oxide donor, nitric oxide precursor, inhibitor of a nitric oxide synthase inhibitor, and / or an activator of nitric oxide synthase. Methods may include the treatment of various disease states by inhibiting Aldose Reductase.

The invention discloses a preparation method of sophora flower buds both used as medicines and foods and relates to the field of processing of foods both used as medicines and foods. The preparation method comprises the following steps: washing fresh sophora flower buds; baking the sophora flower bud at 35 DEG C to 45 DEG C for 1.5h to 2h; then baking at 75 DEG C to 85 DEG C for 1h; then frying at110 DEG C to 120 DEG C for 35min to 45min; then cooling to 10 DEG C to 15 DEG C within 5min to 10min; sealing. According to the preparation method disclosed by the invention, different baking temperature and different baking time are adopted, and water, bitter glycoside, triterpenoid saponin, sophoradiol and volatile oil in the sophora flower buds are released or decomposed in sequence under three temperature gradients; meanwhile, flavonoid, betulin, rutin, vitamin P and inhibiting aldose reductase, which have a main health-care effect, in the sophora flower buds are protected through technology operation including rapid cooling and sealing, so that the sophora flower buds are combined with the health-care effect of the other components.

The present disclosure provides compositions and methods related to the fermentation of xylose. Host cells having recombinant polynucleotides encoding one or more of aldose reductases, xylitol dehydrogenases, and xylulokinase are provided herein. Host cells having reduced expression of PHO13 are also provided herein. Also provided herein are uses of host cells provided herein, and methods relating to the use of xylose-containing materials.

The invention discloses a pharmaceutical composition for treating diabetes and indications thereof. The effective component of the medical composition for diabetes and indications consists of a medicinal extract, a coenzyme Q and folic acid. The medicinal extract consists of extracts of radix curcumae, rheum officinale, rhizoma curcumae longae, aloe and Polygonum cuspidatum. The medical composition for treating diabetes and indications can greatly inhibit the activities of three target enzymes: alpha-glucosidase, hexokinase and aldose reductase, and can effectively inhibit rise of blood sugar and blood fat in a diabetic animal model as well as treat indications induced by diabetes such as hyperlipidemia and retinopathy.

This invention relates to methods for determining the risk of developing cataract in mammals, and, more specifically, in mammals, including humans, with non-insulin dependent diabetes. The methods are performed by determining the presence or absence of genetic markers in genomic DNA. The presence of a Z-2 allele, a microsatellite marker of the aldose reductase, is indicative of an increased risk for developing cataract. The presence of Z-4, a microsatellite allele of the aldose reductase gene, indicates a decreased risk for developing cataract. The methods comprise nucleic acid probes that hybridize to a nucleic acid encoding the microsatellite region of the mammalian aldose reductase gene. The probes may also be immobilized on a solid support to form a microarray. In addition, this invention is directed to methods for treating a mammal with a genetic predisposition for developing cataract; following a screening method that detects a Z-2 microsatellite marker of an aldose reductase gene the mammal is treated with an inhibitor of aldose reductase.

A diphenyldienyl ketone is disclosed, which can be used to prepare medicine for preventing, treating and relaxing the complecations of diabetes.

The present invention provides a protective agent for retinal nerve or optic nerve which exerts its effect through a different mechanism from that of conventional therapeutic agents and can be taken for long periods. The present invention is the protective agent for retinal nerve or optic nerve which comprises a compound with aldose reductase inhibiting activity such as the compound represented by the following general formula as an active ingredient. A preferable compound thereof is (2S,4S)-6-fluoro-2′,5′-dioxospiro[chroman-4,4′-imidazolidine]-2-carboxamide:wherein X represents a halogen atom or a hydrogen atom, R1 and R2 independently represent a hydrogen atom or an optionally substituted C1 to C6 alkyl group, or R1 and R2, together with a nitrogen atom bound thereto, or optionally another nitrogen atom or an oxygen atom, are combined to form a 5- to 6-membered heterocycle.

The present disclosure provides a composition for enhancing effect of an inhibitor in inhibiting NAD+ / NADP+ or NADH / NADPH dependent enzymes. The inhibition of the NAD+ / NADP+ or NADH / NADPH dependent enzymes such as Enoyl-ACP reductase (ENR) by the composition of the present disclosure serves as a target for treating malaria and other infectious diseases. The present disclosure provides composition comprising inhibitor and polyphenol, wherein the polyphenol was found to enhance the inhibitory activity of the inhibitor. The present disclosure provides method for treating an infectious disease comprising administering an effective amount of the composition of the present disclosure to patients in need thereof. The present disclosure further provides a method for identifying a compound that enhances the effect of the inhibitor, a method of determining the antimalarial activity of a compound and use of polyphenol as a bioenhancer that enhances effect of an inhibitor for inhibiting NAD+ / NADP+ or NADH / NADPH dependent enzymes. The present disclosure provides a composition comprising inhibitor and a polyphenol wherein the polyphenol enhances effect of the inhibitor for inhibiting aldose reductase for treating complications of diabetes that include diabetic retinopathy, cataract neuropathy and neural complication.