36 results about "Biopterin" patented technology

The invention describes a pharmaceutical composition and method for treating cancer comprised of A) 2,3-dimethoxy-5-methyl-1,4-benzoquinone and / or B) at least one of wild yam root, teasel root, balm of gilead bud, bakuchi seed, dichroa root, kochia seed, kanta kari, bushy knotweed rhizome, arjun, babul chall bark, opopanax and bhumy amalaki; optionally one or more of frankincense, garcinia fruit, vitex, dragons blood, mace, sage and red sandalwood with at least c) one compound capable of maximizing oxidative mitochondrial function preferably riboflavin or vitamin B2 derivatives, FAD, FMN, 5-amino-6-(5′-phosphoribitylamino)uracil, 6,7-Dimethyl-8-(1-D-ribityl)lumazine, ribitol, 5,6-dimethylbenzimidazole, tetrahydrobiopterin, vitamin B1, lipoic acid, biotin, vitamin B6, vitamin B12, folate, niacin, vitamin C and pantothenate and / or d) at least one lactic acid dehydrogenase inhibitor (preferably 2′,3,4′5,7-pentahydroxyflavone) and optionally f) an alkalizing agent (aloe vera, chlorella, wheat grass, sodium or potassium bicarbonate, potassium) g) an antiproliferative herb (speranskia or goldenseal) and h) a pharmaceutically acceptable carrier.

Disclosed herein are analogs of tetrahydrobiopterin, compositions containing the same, and methods of treating an individual suffering from a condition responsive to tetrahydrobiopterin by administration of the analog. These analogs are contemplated for use wherever tetrahydrobiopterin is currently used to treat conditions responsive to tetrahydrobiopterin therapies.

The use of tetrahydrobiopterine and the derivatives thereof in the production of a medicament to improve protein tolerance for the treatment of diseases arising from an amino acid metabolic disorder, e.g. hyperphenylalaninemia. The invention also relates to a composition which contains tetrahydrobiopterine or derivatives thereof in addition to a special mixture of amino acids. The invention can, for instance, be used as a food which is low in phenylalanine in the complete nutrition of hyperphenylalaninemic patients. Tests carried out within the text of said invention revealed that by treating the context of said invention revealed that by treating patients who had phenylalanine concentrations of more than 200 μmol / l in their blood with tetrahydrobiopterine, it was possible to reduce the concentrations of phenylalanine by 37% to 92%.

The present invention provides a transformed cell which is transformed by at least one gene of enzymes participating in biosynthesis of tetrahydrobiopterin and a process for the production of a biopterin compound using the same. In accordance with the present invention, the biopterin compound can be produced in large quantities in an industrial advantageous manner from less expensive materials.

The invention describes a nutraceutical composition and method for preventing / treating cancer or augmenting chemotherapy in advanced stage malignancies; comprised of [1] tumoricidal herbs; beth root, galbanum, gromwell root, wild yam, balm of gilead bud, frankincense, [2] an antiproliferative herb; speranskia [3] a natural lactic acid dehydrogenase (LDH) inhibitor, 2′,3,4′5,7-pentahydroxyflavone or cinnamon, [4] alkalizing agents: calcium, magnesium, potassium or bicarbonate salts, barley grass, chlorella and spirulina [5] at least one quinone and [6] at least one agent capable of maximizing oxidative mitochondrial function preferably riboflavin, 6,7-Dimethyl-8-(1-D-ribityl)lumazine, ribitol, 5,6-dimethylbenzimidazole, tetrahydrobiopterin and a pharmaceutically acceptable carrier.

An assay for a GCH1 allele and associated genotype for the screening, prediction, diagnosis, prognosis, treatment and treatment response of psychiatric, neuropsychiatric, and neurological disorders, such as schizophrenia, schizoaffective disorder and bipolar disorder, and for defining treatments of such disorders. The presence of a variant in the GCH1 gene, alone or in conjunction with a measurement of low or altered biopterin, or altered BH4 system measures, is used to screen for or diagnose subjects at high risk for developing a psychiatric, neuropsychiatric, or neurological disorders. The assay of the GCH1 genotype, with or without biopterin or a BH4 or BH4 system assay, may also be used to determine antipsychotic or mood stabilizer medication, as well as other treatments. For subjects with an impaired BH4 system, treatments to increase or normalize biopterin, BH4, or the BH4 system can also be used, such as BH4 supplementation, lithium treatment, phenylalanine treatment, or other treatments and therapies.

The invention discloses an accurate, quick and high-throughput method for detecting neopterin and biopterin in the urine of a human body. The method comprises the following steps: analyzing a urine sample which is pre-treated by liquid chromatography on a chromatographic column which is a reverse bonded silica gel column; performing gradient elution with a mobile phase which is methanol and ammonium acetate buffer solution; and detecting with a fluorescent detector. The method is low in cost and simple in pre-treatment, can realize batch-processing detection to optimize the chromatographic process, shorten the analyzing time and greatly improve the throughput of sample, and is especially suitable for requirement of clinical and daily detection for the chromatographic process.

To provide a method for producing L-biopterin on a large industrial scale by using a reagent which is inexpensive and easy to handle, without requiring a use of any particular equipment or plants.A method for porducing a biopterin derivative represented by the formula (6):wherein R1 and R2, which are the same or different from each other, each represents a hydrogen atom, an alkyl group, or an aryl group, comprising:reacting a compound belonging to triacetoxy-5-deoxy-L-arabinose phenylhydrazones represented by the formula (4):wherein R1 and R2 are the same as defined above,with 6-hydroxy-2,4,5-triaminopyrimidine (5) under catalytic influence of a Lewis acid in an aqueous solvent.

The invention provides a method for detecting biopterin in a marine water body. The method comprises the following steps of: performing pretreatment, specifically, filtering a water sample, discardinga filtrate, taking particulate matters, adding a cell lysis solution crush the particulate matters to obtain a dissolved liquid, adjusting the pH value of the dissolved liquid, and performing extraction to obtain a water phase containing biopterin; and 2) detecting the water phase containing the biopterin by using reversed-phase high performance liquid chromatography. According to the reversed-phase high performance liquid chromatography, isocratic elution is adopted, and mobile phases are methanol and water. According to the method for detecting the content of the biopterin in the marine water body provided by the embodiment of the invention, the pretreatment under specific conditions is carried out; detection sensitivity is effectively improved; the detection limits of the method are further reduced; the method can adapt to the current situation that the content of the biopterin in the marine water body is low; the method has high accuracy; and the method has important significancein revealing the regulation and control process of biopterin in marine plankton, especially the life activity of microorganisms, and strengthening the understanding of marine chemistry.

The invention relates to a preparation method of L-erythro biopterin used as an import preparation intermediate body of a clinically used medicament (R)-2-amido-6-[(1R,2S)-1,2-dihydroxy propyl]-5,6,7,8-tetrahydro-4(3H)-pteridine ketone hydrochloride for treating atypical hyperphenylalaninemia, which belongs to the technical field of medicinal chemistry. The preparation method sequentially comprises the steps of: reacting L-(+)-arabinose 1 with alcohol by glycosidation; adding sulfonyl chloride for generating a sulfonation reaction; reducing and removing sulfonyl ester; removing reduced aldehyde protective groups; reacting with hydrazine for obtaining a hydrazine compound; reacting with estolide or the sulfonyl chloride; reacting with 2,4,5-3-amino-pyrimidine ketone; adding an oxidant; and removing acyl for obtaining L-erythro biopterin. The invention ensures deodorizing equipment is not installed on a reaction system by utilizing Odourless mercaptan thereby reducing production cost and optimizing a working environment; and the invention has mild reaction condition of each step and easy operation, and shortens a production period.

The invention discloses recombinant escherichia coli for producing melatonin, and a construction method and application of the recombinant escherichia coli. The invention first discloses the recombinant escherichia coli, and compared with receptor escherichia coli, the recombinant escherichia coli has the advantages that the expression amount of a gene of a melatonin biosynthesis-related protein is increased, and / or the content of the melatonin biosynthesis-related protein is increased, and / or activity of the melatonin biosynthesis-related protein is increased, wherein the melatonin is selected from at least one of phenylalanine hydroxylase, dihydromonophosphate reductase, 4alpha-hydroxytetrahydrobiopterin dehydratase, aspartate transaminase family protein, N-acetyltransferase and caffeicacid-O-methyltransferase.and further discloses a construction method and application of the recombinant escherichia coli. The recombinant escherichia coli strain for producing melatonin has melatoninsynthesis efficiency is obviously higher than other existing strains, and has great significance for industrial production and large-scale application of melatonin.

It is thought that applications and use of tetrahydrobiopterin (BH4), which is used as a pharmaceutical, will expand due to its superior efficacy. However, in addition to BH4 being extremely expensive, since it is unstable with respect to oxidation, applications other than pharmaceuticals are considered to be difficult. Further, it is difficult for BH4 to permeate through a blood-brain barrier, so that BH4 concentrations in the brain tend not to increase under the present conditions. Biopterins are oxidized form of BH4, stable to oxidation, easy to handle, and can be produced inexpensively. The inventors found that administration of biopterin can be expected to demonstrate effects equal to or greater than those of administration of BH4. On the basis of the result, it was first clarified that administration of a composition containing biopterin causes increase in BH4 concentration in the body (especially BH4 concentration in the brain, which is difficult to be increased by BH4 administration) to demonstrate sufficient actions.

Biopterins are useful compounds utilized in pharmaceutical agents or functional foods. The presence of sepiapterin reductase (SPR) involved in the biosynthesis of biopterins has not been confirmed so far in microorganisms except for a few microorganisms such as blue-green algae. For efficiently producing biopterins using microorganisms, it has been demanded to obtain and use SPR genes derived from microorganisms. The present inventors have found that when Saccharomyces cerevisiae or Escherichia coli is transformed with a YIR035C gene from Saccharomyces cerevisiae or a yueD gene from Bacillus subtilis, the transformed microorganism secretes biopterins into a culture solution. Based on this finding, the present invention provides a polypeptide, DNA encoding the polypeptide, a recombinant vector comprising the DNA, and a transformant obtained by transformation with the vector, which are useful in biopterin production using microorganisms. Moreover, the present invention provides a method for efficiently producing biopterins using the transformant.

The present invention features pharmaceutical compositions including sepiapterin, or a pharmaceutically acceptable salt and / or co-crystal thereof, and methods for the treatment of tetrahydrobiopterin-related disorders (e.g., tetrahydrobiopterin deficiency or phenylketonuria) with such compositions.

The present invention relates to new pharmaceutical salts and / or co-crystals of sepiapterin which exhibit improved properties. In particular, the invention relates to salts of sepiapterin with improved stability. The invention also relates to pharmaceutical compositions including a pharmaceutically effective amount of one or more salts and / or co-crystals of sepiapterin, as well as methods of treating tetrahydrobiopterin-related disorders including administration of a sepiapterin salt and / or co-crystal of the invention to a subject in need thereof.

The invention relates to a preparation method of an L-erythro biopterin compound, wherein the L-erythro biopterin compound has a structure as shown in a formula (I), and the L-erythro biopterin compound as shown in the formula (I) is mainly prepared from a compound with a structure as shown in a formula (II) or a formula (III) through a dihydroxylation reaction. The preparation method of the L-erythro biopterin compound is high in production efficiency, low in cost, green, environmentally friendly and suitable for industrial production.

The invention relates to an intermediate for preparing an L-red biopterincompound and a preparation method thereof, wherein the intermediate has a structure shown as a formula (IVa-1), a formula (IVa-2), a formula (IVa-3) or a formula (IVa-4), and the formulas (IVa-1), (IVa-2), (IVa-3) and (IVa-4) are defined in the specification. According to the invention, the intermediate and the preparation method thereof effectively realize the effects of one-pot resolution and purification, are simple and convenient to operate, can greatly reduce the production cost, and are particularly suitable for preparing L-red biopterin compounds.

Disclosed herein are analogs of tetrahydrobiopterin, compositions containing the same, and methods of treating an individual suffering from a condition responsive to tetrahydrobiopterin by administration of the analog. These analogs are contemplated for use wherever tetrahydrobiopterin is currently used to treat conditions responsive to tetrahydrobiopterin therapies.

Crystalline solids A to E of biopterin are distinguished from each other by diffraction angle in an X-ray powder diffraction pattern measured using Cu—Kα radiation. The crystalline solid A is characterized by strong peak at 4.6° and peaks at 13.6°, 18.1° and 27.5°; the crystalline solid B is characterized by strong peak at 4.85° and peaks at 2.4°, 13.2°, 18.1° and 27.3°; the crystalline solid C is characterized by strong peak at 5.35° and peaks at 10.8°, 21.9° and 27.3°; the crystalline solid D is characterized by strong peak at 5.1° and peaks at 2.6°, 9.2°, 13.4°, 15.4°, 18.3°, 21.8° and 27.3°; and the crystalline solid E is characterized by strong peaks at 4.5° and 5.8°, and peaks at 10.6°, 15.6°, 20.0°, 20.7°, 23.8° and 27.3°.

The invention provides an application of an exosome metabolite as a bipolar affective disorder marker. Specifically, the invention provides application of a reagent material and / or instrument equipment for detecting the exosome metabolite level in a sample from an individual to be detected in preparation of a detection system for diagnosing the bipolar affective disorder disease risk, and the exosome metabolite comprises phosphoric acid, chenodeoxycholic acid, lysophosphatidylethanolamine 14:0, N-acetyl methionine, 13-oxo-9Z,11E-octadecadienoic acid, glycine, 1-naphthylacetic acid, 2-aminoethanesulfonic acid / taurine, D-2-aminobutyric acid, biopterin, glucosamine, lysophosphatidylcholine 18:0, lysophosphatidylethanolamine 18:0, lysophosphatidylcholine 20:1, and PAF C-16. According to the invention, positive help can be provided for pathogenesis of bipolar affective disorder and research of new targeted therapy means.

Methods for delivering a heterologous gene to a mammalian subject using recombinant adeno-associated virus (rAAV) virions are described. Recombinant AAV virions containing a heterologous gene encoding a metabolic protein are delivered to a mammalian subject having a metabolic disorder. The rAAV virion-delivered heterologous gene is expressed at a therapeutic level thereby ameliorating a sign or symptom of the metabolic disease. Exemplary examples of metabolic diseases are those caused by defects in aromatic amino acid metabolism. Exemplary examples of heterologous genes include those encoding an aromatic amino acid hydroxylase, aromatic amino acid decarboxylase, and enzymes involved in tetrahydrobiopterin synthesis. Methods for treating phenylketonuria are also described.

An assay for a GCH1 allele and associated genotype for the screening, prediction, diagnosis, prognosis, treatment and treatment response of psychiatric, neuropsychiatric, and neurological disorders, such as schizophrenia, schizoaffective disorder and bipolar disorder, and for defining treatments of such disorders. The presence of a variant in the GCH1 gene, alone or in conjunction with a measurement of low or altered biopterin, or altered BH4 system measures, is used to screen for or diagnose subjects at high risk for developing a psychiatric, neuropsychiatric, or neurological disorders. The assay of the GCH1 genotype, with or without biopterin or a BH4 or BH4 system assay, may also be used to determine antipsychotic or mood stabilizer medication, as well as other treatments. For subjects with an impaired BH4 system, treatments to increase or normalize biopterin, BH4, or the BH4 system can also be used, such as BH4 supplementation, lithium treatment, phenylalanine treatment, or other treatments and therapies.

The invention discloses recombinant escherichia coli for producing N-acetyl-5-hydroxytryptamine, and a construction method and application of the recombinant escherichia coli. The invention firstly discloses the recombinant escherichia coli, and compared with a receptor escherichia coli, the recombinant escherichia coli has the advantages that the expression level of a gene of a tryptophan derivative synthesis related protein is increased and / or the content of the tryptophan derivative synthesis related protein is increased and / or the activity of the tryptophan derivative synthesis related protein is increased, wherein the tryptophan derivative synthesis related protein is selected from at least one of phenylalanine hydroxylase, dihydromonophosphate reductase, 4[alpha]-hydroxytetrahydrobiopterin dehydratase, aspartate transaminase family proteins and N-acetyl transferase. The invention further discloses the construction method and application of the recombinant escherichia coli. The N-acetyl-5-hydroxytryptamine synthesis efficiency of the recombinant escherichia coli for producing the N-acetyl-5-hydroxytryptamine is obviously higher than synthesis efficiency of other existing strains, and the recombinant escherichia coli has great significance for industrial production and large-scale application of N-acetyl-5-hydroxytryptamine.

The invention discloses an accurate, quick and high-throughput method for detecting neopterin and biopterin in the urine of a human body. The method comprises the following steps: analyzing a urine sample which is pre-treated by liquid chromatography on a chromatographic column which is a reverse bonded silica gel column; performing gradient elution with a mobile phase which is methanol and ammonium acetate buffer solution; and detecting with a fluorescent detector. The method is low in cost and simple in pre-treatment, can realize batch-processing detection to optimize the chromatographic process, shorten the analyzing time and greatly improve the throughput of sample, and is especially suitable for requirement of clinical and daily detection for the chromatographic process.

The invention provides a method for detecting biopterin in marine water, comprising the following steps: pretreatment: discarding the filtrate after filtering the water sample, taking particulate matter and adding cell lysate to break it to obtain a stripping solution; adjusting the pH of the stripping solution, After extraction, the aqueous phase containing biopterin is obtained; 2) the aqueous phase containing biopterin is detected by reverse-phase high-performance liquid chromatography; wherein, the reverse-phase high-performance liquid chromatography adopts isocratic elution, and the mobile phase is methanol and water. The method for detecting the content of biopterin in marine water provided by the embodiments of the present invention can effectively improve the detection sensitivity and further reduce the detection limit through the pretreatment of specific conditions, and can adapt to the current situation of low content in marine water, and has high accuracy. It is of great significance to reveal the regulation process of biopterin in marine plankton, especially the life activities of micro organisms, and to strengthen the understanding of marine chemistry.

The invention relates to a preparation method of L-erythro biopterin used as a preparation intermediate body of a clinically used medicament (R)-2-amido-6-[(1R, 2S)-1,2-dihydroxy propyl]-5,6,7,8-tetrahydro-4(3H)-pteridine ketone hydrochloride for treating atypical hyperphenylalaninemia, which belongs to the technical field of medicinal chemistry. The preparation method sequentially comprises the steps of: reacting L-(+)-arabinose 1 with alkyl hydrosulfide by acetalization; adding sulfonyl chloride for generating a sulfonation reaction; reducing and removing sulfonyl ester; removing reduced sulfur aldehyde protective groups; reacting with hydrazine for obtaining a hydrazine compound; reacting with estolide or the sulfonyl chloride; reacting with 2,4,5-3-amino-pyrimidine ketone; adding an oxidant; and removing acyl for obtaining the L-erythro biopterin. The invention ensures deodorizing equipment is not installed on a reaction system by utilizing Odourless mercaptan, thereby saving costand optimizing a working environment; and the invention has mild reaction condition of each step, short period and easy operation.

The invention discloses a recombinant Escherichia coli producing N-acetyl-5-serotonin, a construction method and application thereof. The present invention firstly discloses recombinant Escherichia coli, compared with the recipient Escherichia coli, the expression level of genes related to synthesis of tryptophan derivatives is increased and / or the content of proteins related to synthesis of tryptophan derivatives is increased and / or Or the activity of the tryptophan derivative synthesis-related protein is increased; the tryptophan derivative synthesis-related protein is selected from at least one of the following: phenylalanine hydroxylase, dihydromonophosphate reductase, 4a-hydroxy Tetrahydrobiopterin dehydratase, aspartate aminotransferase family proteins, and N‑acetyltransferase. The construction method and application of the recombinant Escherichia coli are further disclosed. The N-acetyl-5-serotonin-producing recombinant Escherichia coli N-acetyl-5-serotonin synthesis efficiency of the present invention is significantly higher than other existing strains, and has great significance for the industrial production and large-scale application of N-acetyl-5-serotonin.

The present invention relates to a method of treating a disease in a subject, comprising administering to a subject in need thereof a solid pharmaceutical composition biopterin derivatives.

The invention discloses a recombinant escherichia coli producing melatonin, a construction method and application thereof. The present invention firstly discloses recombinant Escherichia coli, compared with the recipient Escherichia coli, the expression level of the gene related to melatonin biosynthesis is increased and / or the content of the melatonin biosynthesis-related protein is increased and / or the The activity of the melatonin biosynthesis-related protein is increased; the melatonin is selected from at least one of the following: phenylalanine hydroxylase, dihydromonophosphate reductase, 4a-hydroxytetrahydrobiopterin dehydratase, Aspartate transaminase family proteins, N‑acetyltransferase and caffeic acid‑O‑methyltransferase. The construction method and application of the recombinant Escherichia coli are further disclosed. The melatonin-producing recombinant Escherichia coli strain of the invention has significantly higher melatonin synthesis efficiency than other existing strains, and is of great significance to the industrialized production and large-scale application of melatonin.

The present invention features pharmaceutical compositions including sepiapterin, or a pharmaceutically acceptable salt and / or co-crystal thereof, and methods for the treatment of tetrahydrobiopterin-related disorders (e.g., tetrahydrobiopterin deficiency or phenylketonuria) with such compositions.