80 results about "Deoxynojirimycine" patented technology

The present invention provides a method for increasing the activity of a mutant or wild-type α-glucosidase enzyme in vitro and in vivo by contacting the enzyme with a specific pharmacological chaperone which is a derivative of 1-deoxynojirimycin. The invention also provides a method for the treatment of Pompe disease by administration of chaperone small molecule compound which is a derivative of 1-deoxynojirimycin. The 1-deoxynojirimycin derivative is substituted at the N or C1 position. Combination therapy with replacement α-glucosidase gene or enzyme is also provided.

Imino sugars, such as deoxynojirimycin (DNJ), are glucose analogues that selectively inhibit cellular α-glucosidase I and II (enzymes that process N-linked glycans in glycoprotein) and exhibit broad spectrum antiviral activities against many enveloped viruses. Previously we have reported a novel DNJ derivative, OSL-95II, with antiviral activity and reduced cytotoxicity. In order to develop imino sugars with more potent antiviral activity as well as improved toxicity profile, OSL-95II was modified by diversifying the nitrogen linked alkylated side chain. The antiviral activities were initially tested in bovine viral diarrhea virus (BVDV) infected MDBK cells, yielding several imino sugar derivatives with novel structure and superior antiviral activity and toxicity profile. Furthermore, these new compounds were shown to be active against Dengue virus (DV) and West Nile virus (WNV) infection in BHK cells where potent anti-DV activity having submicromolar EC50 values and SI of greater than 900. These compounds represent a new generation of iminio sugars and their analogues, having application in the clinical treatment of infection of DV and other members of flaviviridae.

The present invention relates to a mulberry leaf effective component composition for reducing blood sugar and its preparation method. Said mulberry leaf effective component composition contains 20-80% of mulberry leaf polysaccharide and 80-20% of mulberry leaf alkaloid in which 1-deoxynojirimycin content is greater than 50%. Said preparation method includes the following steps: removing impurity, drying, pulverizing to obtain mulberry leaf powder, using organic solvent to make extraction, filtering, removing residue, using hot water to make extraction, filtering, adding ethyl alcohol into filtrate to make its concentration be 40%-80%, filtering to obtain supernatant fluid and precipitate, using cation exchange resin and anion exchange resin to make separation and remove impurity, concentrating and drying so as to obtain mulberry leaf alkaloid.

The present invention provides a method for increasing the activity of a mutant or wild-type α-glucosidase enzyme in vitro and in vivo by contacting the enzyme with a specific pharmacological chaperone which is a derivative of 1-deoxynojirimycin. The invention also provides a method for the treatment of Pompe disease by administration of chaperone small molecule compound which is a derivative of 1-deoxynojirimycin. The 1-deoxynojirimycin derivative is substituted at the N or C1 position. Combination therapy with replacement α-glucosidase gene or enzyme is also provided.

The invention relates to a technology for extracting and separating active ingredients of traditional Chinese medicines, in particular to a method for extracting and separating high-purity 1-deoxynojirimycin from folium mori, which comprises the following steps of: extracting a powder material by using an aqueous solvent, filtering off dregs, and centrifuging the material to obtain extracting solution; concentrating the extracting solution until ethanol does not exist, and filtering by using an ultrafiltration membrane; regulating the pH to be 3.0-4.0 by using inorganic acid, precipitating, and centrifuging to removing impurities; applying acidified feed to a strong acid cation resin column, washing with water, and eluting by using ammonia water; applying feed liquid to a porous resin column, washing with water, performing gradient elution by using ethanol with different concentrations, and collecting target eluent; concentrating the target eluent under reduced pressure, and drying to obtain a crude product; dissolving the crude product by using absolute ethanol, making the solution pass through an alkaline adsorbing column to remove impurities, and collecting effluent liquid; and concentrating the effluent liquid under reduced pressure, and performing normal temperature crystallization and recrystallization to obtain the refined 1-DNJ product. In the whole technological process, except ethanol, other organic solvents are not used, the operation is safe, and the 1-DNJ content can reach 98.3 percent.

The invention discloses sanggenone C and sanggenone D extracted from white mulberry root-barks, mulberry twigs and folium leaves and a new medicine application of a composition comprising the sanggenone C and the sanggenone D which are main ingredients, particularly the application of the single ingredient sanggenone C or sanggenone D and the composition composed of the sanggenone C, the sanggenone D, mulberrin, mulberroside, oxidized resveratrol, resveratrol and deoxynojirimycin in preparation of alpha-glucosidase inhibitor medicines. The composition is prepared by respectively extracting medicinal materials containing the chemical components above and blending according to certain proportions, or using several extraction methods for extracting the medicinal materials simultaneously containing the chemical components above. The white mulberry root-barks, the mulberry twigs and the folium leaves are accidentally found to contain the sanggenone C and the sanggenone D apart from containing alkaloids such as deoxynojirimycin; and the sanggenone C and the sanggenone D have stronger pharmacological activity than the alkaloids such as deoxynojirimycin.

The invention discloses a method for extracting a deoxynojirimycin monomer. The method comprises the following steps of: soaking a mulberry raw material in acidic aqueous solution, and extracting for 1 to 3 times; adsorbing extracting solution on a cation exchange resin, washing, and eluting by using ammonia water; performing reverse osmosis pre-concentration on eluent, recovering ammonia, dissolving an intermediate in a hydrophilic solvent, performing catalytic conversion, allowing the solution to pass through a gel chromatographic column, and eluting the hydrophilic solvent; recovering the solvent, dissolving in a mixed solvent, allowing the mixed solvent to pass through the chromatographic column, and eluting the mixed solvent; and recovering the mixed solution to obtain pure deoxynojirimycin products. The method is low in energy consumption and environment-friendly, and the pure deoxynojirimycin products with various purity grades of 10 percent, 50 percent, 99 percent and the like.

A 1-deoxynojirimycin preparing method suitable for industrial production comprises the following steps: (1) raw material pre-treatment: crushing the dry mulberry leaf raw material; (2) enzymelysis: adding water into powder, raising the temperature, adding a combined enzyme for enzymelysis, and filtering; (3) continuous combined extraction: performing continuous combined extraction on filter residues by using 3-4 extracting devices, mixing extracting solutions, and filtering; (4) alcohol precipitation and centrifugation: performing pressure-reduction concentration to 1 / 3-1 / 2 of the original volume, cooling, adjusting pH, adding an alcohol solution, stirring, performing still standing, and centrifuging by using a tube centrifuge; (5) membrane filtration: at 25-35 bar pressure at room temperature, ultrafiltering by using an organic ultrafiltration membrane, and then at 0.5-1.5 MPa pressure at room temperature, nano-filtering by using a nanofiltration membrane; (6) concentrating; (7) drying. By using the 1-deoxynojirimycin preparing method, the loss of a solvent can be reduced to a large extent, the energy consumption can be reduced and the product yield can be increased; therefore, the 1-deoxynojirimycin preparing method is suitable for industrial production.

The invention relates to the use of a deoxynojirimycin derivative, or pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of insulin resistance, hyperpigmentation and / or inflammatory processes in the skin, a fungal disease, overweight and obesity, or a microbacterial infection.

The invention belongs to the field of natural product chemistry, and relates to a method for preparing 1-deoxynojirimycin by a membrane separation technology. The method comprises the following steps of collecting fresh mulberry leaves, drying, crushing, adding deionized water into the crushed mulberry leaves for soaking, adding the soak into a nanofiltration membrane system with filtration to carry out filtration, adding the filtrate into a reverse osmosis membrane to carry out concentration, adding ethyl acetate into the concentrated filtrate to carry out extraction, carrying out pressure-reducing concentration of an aqueous phase obtained by the previous step, and carrying out vacuum drying to obtain the desired product. The method for preparing 1-deoxynojirimycin by a membrane separation technology has the advantages of simple process, good operability, low energy consumption, less pollution and good applicability for industrialized production.

The present invention relates to a polypeptide associated with the biosynthesis of 1-deoxynojirimycin which is a substance that inhibits a-glucosidase activity, to a polynucleotide coding therefor, to a vector comprising the polynucleotide, to a transformant comprising the vector, and to a method in which the transformant is used in order to produce either a polypeptide associated with the synthesis of 1-deoxynojirimycin or 1-deoxynojirimycin. The polynucleotide of the present invention can be used in the volume production of 1-deoxynojirimycin, or can be used in studies searching for novel 1-deoxynojirimycin derivatives using recombinant technology, and hence is useful in developing pathogenic virus inhibitors and hypoglycaemic agents for diabetic patients.

The invention discloses a food for improving hyperglycemia and hyperlipidemia of a diabetic patient and a preparation method thereof. The preparation method includes steps of mixing, drying and crushing red yeast rice powder, tartary buckwheat powder and mulberry fruit juice. The preparation method is simple. By means of lovastatin in the red yeast rice powder, total flavonoids in tartary buckwheat, 1-deoxynojirimycin in mulberry fruits and components such as various amino acids in a formula, blood glucose and blood fat can be inhibited or reduced. According to the formula, three raw materials are employed cooperatively so that a blood glucose reducing effect and a blood fat reducing effect can be improved. In addition, the mixture composed of the red yeast rice powder, the tartary buckwheat extract and the mulberry fruit juice provided in the invention can be used as a raw material. With addition of pharmaceutically acceptable auxiliary materials or components, the raw material can be prepared into tablets, capsules, granules, granular tea or the like. The food has a huge medicinal and health-caring value.

The invention belongs to the field of detection of quality of traditional Chinese preparations, and particularly relates to a method for detecting a pharmaceutical preparation for treating the xiaoke disease. The pharmaceutical preparation comprises the active pharmaceutical ingredients, by weight, 6000-8000 parts of silkworm feces and 100-200 parts of radix glycyrrhizae. According to the method for detecting the pharmaceutical preparation, the pharmaceutical preparation is detected by measuring the content of 1-Deoxynojirimycin through an HPLC method. The method for detecting the pharmaceutical preparation is rapid, comprehensive and highly targeted, the quality of the preparation can be effectively controlled, and use safety and stability of the preparation can be improved.

The invention discloses a medicine composition and application thereof, and a medicament containing the medicine composition. The medicine composition comprises moraceae morus plant total alkaloids and balsam pear total saponins, wherein the mass content ratioof the moraceae morus plant total alkaloids and the balsam pear total saponins is 1:2-7:1; the moraceae morus plant total alkaloids are used in the form of moraceae morus plant extracts in the medicine composition, and the balsam pear total saponins are used in the form of balsam pear extracts in the medicine composition; the moraceae morus plant total alkaloids comprise 1-deoxynojirimycin, and the mass content of the 1-deoxynojirimycin in the moraceae morus plant extracts is 2-50%. Target components are extracted from natural plants; the medicine composition has excellent effects of decreasing blood-glucose, losing weight, and reducing lipid in a synergetic manner, and is particularly suitable for the treating and preventing type 2 diabetes.

The invention relates to the field of traditional Chinese medicine active site preparation, and discloses an active site of a mulberry twig, as well as a preparation method and application thereof. The method comprises the following steps: S1, after grinding the mulberry twig, heating, reflowing and extracting for 1-3 times at the temperature of 25-100 DEG C with 10-40 times of 25-95% ethyl alcohol, wherein the every-time extraction time is 60-300 min; filtering and concentrating an extracting solution to obtain a stock solution; S2, enriching and purifying the stock solution by strong-acid cation exchange resin and anion exchange resin in sequence to obtain the active site of the mulberry twig. The preparation method is simple and convenient to operate and good in repeatability, and the content of 1-Deoxynojirimycin (1-DNJ ) can be higher than 30.0%.

The invention discloses a preparation method of high-purity 1-deoxynojirimycin. 1-deoxynojirimycin is enriched by using ammonium cation exchange resin, and the 1-deoxynojirimycin is pulped and purified by combining anion exchange resin and a hot solvent to prepare the high-purity 1-deoxynojirimycin. The use of a high-concentration acid liquor can be avoided, so that equipment in a production workshop is prevented from being corroded by acids, the production risk is reduced, the energy consumption can be reduced, the solvent loss can be reduced, the product yield can be increased, and finally,the product with the mass content of 1-deoxynojirimycin being greater than 98.0% can be prepared.

The invention relates to application of 1-deoxynojirimycin in the treatment of diabetic cardiomyopathy and liver injury. 1-Deoxynojirimycin is a known potent alpha-glucosidase inhibitor. The applicable field of 1-deoxynojirimycin is widened herein; the use of 1-deoxynojirimycin or its pharmaceutically acceptable salts in the treatment and / or prevention of diabetic cardiomyopathy and liver injury is provided for the first time; experiments show that 1-deoxynojirimycin plays a positive role in myocardial protection aspects, such as lowering cardiac oxidative stress level of a diabetic patient, inhibiting cardiovascular endothelial cell proliferation of the diabetic patient, and inhibiting myocardial fiber proliferation of the diabetic patient; it is expected to develop 1-deoxynojirimycin into drugs to treat diabetic cardiomyopathy, thereby filling the blank of the prior art.

The invention provides a preparation method of mulberry leaf extract containing 1-deoxynojirimycin. The method mainly including the steps of saline solution water-proof cooking and softening, enzymolysis, polyamide column purification and simulated moving bed refining is determined by sufficiently considering the raw material characteristics of mulberry leaves and the dissolution characteristics of the target component 1-deoxynojirimycin and conducting system screening and optimizing. The separation effect is extremely good, and the concentration of 1-deoxynojirimycin in the finally obtained mulberry leaf extract is larger than 95 wt%. All materials used for the whole method are conventional materials, cost is low, yield is high, solvent can be recycled, environment pollution can be reduced, and industrialization can be easily achieved.

The invention discloses a method for extracting 1-deoxynojirimycin from fresh mulberry leaves. The method comprises the following steps: cleaning and draining fresh picked mulberry leaves; cutting thedrained fresh mulberry leaves into strips, and putting the mulberry leaves into an extracting solution containing acetic acid; recovering an extracting solution after ultrasonic treatment; carrying out ultrasonic-assisted extraction on the mulberry leaves twice by taking purified water as an extraction solvent; combining extracting solutions, filtering, concentrating in vacuum, refrigerating, filtering, concentrating and drying to obtain an extract. The method does not need a large amount of organic solvents, and is simple in process, easy to operate and high in extraction rate. The obtainedextract can be used for preparing high-purity 1-deoxynojirimycin.

The invention discloses bacillus amyloliquefaciens capable of producing 1-deoxynojirimycin at high yield. The strain preserved in the China General Microbiological Culture Collection Center with the preservation number of CGMCC No. 19098. The invention also discloses a method for producing the 1-deoxynojirimycin by fermenting the bacillus amyloliquefaciens, and the yield of the 1-deoxynojirimycinreaches 0.9 g / L. The 1-deoxynojirimycin has alpha-glucosidase inhibitory activity and can be applied to blood glucose control of diabetics, so that the strain and the method for preparing the 1-deoxynojirimycin through fermentation of the strain have wide application prospects.

Disclosed are methods of preparing substituted nojirimycins represented by the following formula, comprising reacting 1-deoxynojirimycin with a reagent prepared by reacting an oxidizing agent with the compound represented by the following formula.

The invention discloses mulberry leaf and silkworm chrysalis yellow rice wine, which comprises 1-deoxynojirimycin (DNJ) and total polysaccharides, the content of the 1-deoxynojirimycin (DNJ) is not less than 0.15 mg / L, and the content of the total polysaccharides is more than or equal to 300mg / L. The invention further discloses a preparation-type preparation process of the mulberry leaf and silkworm chrysalis yellow rice wine and a fermentation-type preparation process of the mulberry leaf and silkworm chrysalis yellow rice wine. The mulberry leaf and silkworm chrysalis yellow rice wine disclosed by the invention contains full-nutrition functional components of mulberry leaves and silkworm chrysalis, can effectively supplement nutrition to a human body and has a health-care function.

The invention discloses an Auricularia auricula cultivation material rich in deoxynojirimycin. The cultivation material is prepared from, by weight, 3-5 parts of bean curd residues, 20-25 parts of ramulus mori, 1-2 parts of gypsum powder, 7-9 parts of edible fungus residues, 50-60 parts of peanut shells, 20-30 parts of pineapple peels and 10-16 parts of chelated emulsion. The ramulus mori is addedinto the cultivation material, mixed, stacked and fermented and blended with mulberry leaf extract; rich deoxynojirimycin is given to the cultivation material, so that the nutritional value of the finished product is improved; the raw material disclosed by the invention is scientific and reasonable in compatibility, comprehensive in formula nutrition, good in air permeability of fungus materialsand strong in water-retaining property, and can provide a good growth environment for the black fungus.

The invention belongs to the field of chemical medicaments, particularly relates to use of derivatives of 1-deoxynojiri mycin containing 1,2,3-triazoles as alpha-glucosidase inhibitors. The derivatives of 1-deoxynojiri mycin containing 1,2,3-triazoles have the activity of inhibiting alpha-glucosidase. Therefore, the e derivatives can be used for treating diseases such as diabetes and have a quite wide application prospect.

The invention discloses an oral preparation for slowing down the absorption of an alpha-glycosidase inhibitor and enhancing a hypoglycemic drug effect. The preparation is an oral preparation prepared by adding the following adhesive auxiliary materials based on the certain proportion: carboxymethyl cellulose, hydroxyethyl cellulose, methyl cellulose or beta-cyclodextrin and the like, to each alpha-glycosidase inhibitor (acarbose, voglibose, miglitol, 1-deoxynojirimycin and extract of the 1-deoxynojirimycin). Compared with singly taken alpha-glycosidase inhibitors, the adhesives can be used for prolonging the action time of the alpha-glycosidase inhibitor in the intestine, slowing down the absorption of a medicament and glucose in the intestine and further reducing a plasma concentration, thus the hypoglycemic drug effect is improved. The oral preparation disclosed by the invention can be applied to the prevention and therapy of diseases, such as diabetes, obesity and the like.

The invention provides a mulberry leaf extract rich in 1-deoxynojirimycin and a preparation method of the mulberry leaf extract. The preparation method comprises the following steps: S1, pretreatment: cleaning, drying and crushing mulberry leaves to obtain mulberry leaf powder; s2, ultrasonic treatment: adding the mulberry leaf powder into water, performing ultrasonic treatment and centrifugation, and taking supernate to obtain supernate 1 and residues; s3, performing enzymolysis treatment: adding water with the same mass as the residues, performing enzymolysis by using a compound enzyme 1, performing enzymolysis by using a compound enzyme 2, performing centrifugation, and taking supernate to obtain supernate 2; and S4, filtering, concentrating and drying: combining the supernatant 1 in the S2 and the supernatant 2 in the S3, and carrying out membrane filtration, membrane concentration and spray drying. The mulberry leaf extract obtained by the method is high in extraction rate, retains active ingredients in mulberry leaves to a great extent, has an extremely strong blood sugar reducing effect, is safe, good in quality and light in color, and has plant faint scent.

A stable pharmaceutical composition that includes an active agent selected from 1-deoxynojirimycin, a pharmaceutically acceptable salt thereof, or a derivative thereof, and a buffer, wherein the stable pharmaceutical composition is capable of being parenterally administered to a human without deleterious health effects. Pompe disease is an example of a lysosomal storage disorder. Pompe disease is caused by a deficiency in the enzyme acid alpha-glucosidase (GAA). GAA metabolizes glycogen, a storage form of sugar used for energy, into glucose.

The invention relates to a method for extracting ingredients of white mulberry and in particular relates to a method for extracting deoxynojirimycin from the white mulberry and purifying deoxynojirimycin. The method for extracting deoxynojirimycin from the white mulberry and purifying deoxynojirimycin comprises the following steps: carrying out water extraction, namely airing leaves of the white mulberry, then adding deionized water, boiling at constant temperature and extracting, filtering and collecting filtrate, adding the deionized water into filter residue and then extracting again, putting filtrate together, adding trichloroacetic acid and centrifuging, so that first supernate is obtained; loading onto a column, namely purifying the first supernate by adopting a reversed phase chromatography column, so that liquid containing deoxynojirimycin is obtained; carrying out ethanol precipitation and taking supernate, namely firstly adding ethanol with alcohol content of 55-65% into the liquid containing deoxynojirimycin obtained after the step of loading onto the column is finished, stirring for 3-8 minutes, then adding ethanol with alcohol content of 70-80%, and stirring for 3-5 minutes, so that second supernate is obtained; concentrating, namely concentrating the second supernate, so that concentrated liquor is obtained; and carrying out microwave vacuum drying, namely carrying out microwave vacuum drying on the concentrated liquor, so that a powder product containing deoxynojirimycin is obtained. The method for extracting deoxynojirimycin from the white mulberry and purifying deoxynojirimycin has the advantages of high extraction and purification efficiency and good separating effect.

The invention discloses a determination method of the content of 1-deoxynojirimycin in silkworm larvae. The determination method comprises the following steps of: taking 0.05mol / L HCl as a solvent and swirling for 15-20 seconds at a room temperature; extracting for two times by using a step of ultrasonic treatment for 20-30 minutes to effectively extract DNJ (Deoxynojirimycin) from the silkworm larvae; marking the DNJ for 20-25 minutes at 20 DEG C by utilizing 5mmol / L 9-fluorenyl methylclhlorofonmate (FMOC-C1) to form a DNJ-FMOC complex with the fluorescence; and detecting by utilizing a reverse phase high performance liquid chromatography provided with a fluorescence detector and calculating the content of the DNJ according to a peak area. The determination method of the content of the DNJ in the silkworm larvae provided with the invention has the advantages of high precision, repeatability and high sample recovery rate and good stability, can be used for detecting the content of the DNJ in a lot of silkworm larva products, and has active social benefits and economic benefits for propelling pharmaceutical development of the silkworm larvae.