25 results about "Epiandrosterone" patented technology

The present disclosure relates to the use of cortisol, cortisone, cortisone acetate, hydrocortisone, fludrocortisone, prednisolone, prednisone, methylprednisolone, Dehydroepiandrosterone (DHEA), dexamethasone, betamethasone, adrenocorticotropic hormone (ACTH), ganaxolone, tetracosactide or combinations thereof for preventing and / or reducing the risk of Sudden Unexpected Death in Epilepsy (SUDEP). The disclosure further provides pharmaceutical compositions and methods for preventing and / or reducing the risk of SUDEP, particularly in Dravet Syndrome patients.

The invention relates to a recombinant strain for producing dehydroepiandrosterone and a construction method and application thereof, and belongs to the technical field of biology. According to the genetically engineered bacterium obtained by reducing or eliminating the enzymatic activity of NAD (P) dependent oxidase in an original strain, the DHEA can be directly produced through one-step biological fermentation by taking phytosterol or cholesterol as a substrate. In the genetically engineered bacterium, the activity of sterol-like-isomerase is further reduced or eliminated, and the activities of oxidoreductase, dehydrogenase and ACP-reductase are further reduced or eliminated in a superposed manner, so that the yield of DHEA can be accumulated step by step, the DHEA finally becomes a main product, meanwhile, the proportion of by-products 4-AD and androstenediol is reduced, and the yield of DHEA is increased. The purity is improved while the yield of the DHEA is improved, and subsequent treatment and application are facilitated.

The invention discloses a method for detecting cortisol, testosterone and dehydroepiandrosterone in saliva, and belongs to the field of biological medicine. The technical problem to be solved is to provide a method for accurately detecting cortisol, testosterone and dehydroepiandrosterone in saliva. According to the technical scheme, the method for detecting cortisol, testosterone and dehydroepiandrosterone in saliva is characterized in that a magnetic bead method is adopted for sample pretreatment, a to-be-detected sample is obtained through magnetic bead activation, balancing, sample loading, leaching, elution and nitrogen blowing redissolution, and the to-be-detected sample is detected through a liquid chromatography-tandem mass spectrometry method. The contents of cortisol, testosterone and dehydroepiandrosterone in the sample to be detected are obtained. The detection method is accurate and reliable in detection result, simple, convenient and efficient to operate, and meets industrial practical requirements.

The invention relates to the technical field of organic synthesis of steroid compounds, in particular to a preparation method of androstane-4-ene-3, 6, 17-triketone. Dehydroepiandrosterone acetate is used as an initial raw material to prepare androstane-4-ene-3, 6, 17-triketone through four steps of reactions including chlorohydrination, hydrolysis, oxidation and elimination, the yield and purity of androstane-4-ene-3, 6, 17-triketone are improved, 4-AD impurities are not generated, the total yield of a route reaches 80%, and the purity is larger than or equal to 98.0%; and the preparation process does not involve the use of dangerous chemicals and environment-polluting chromium oxidants, and is suitable for industrial production.

The invention provides a method for preparing dehydroepiandrosterone, which comprises the following steps: S1, taking 4-androstene-3, 17-diketone as a raw material to react to generate 5-androstene-3, 17-diketone; s2, sodium acetate is dissolved in a buffer system, ascorbyl palmitate, L-glutathione, the 5-androstene-3, 17-diketone, ketoreductase, coenzyme and a coenzyme regeneration system are sequentially added for a reaction, and dehydroepiandrosterone is obtained. According to the invention, the ascorbyl palmitate, the L-glutathione and the sodium acetate cooperate to inhibit the side reaction of an intermediate product, active oxygen and the like to generate impurities, so that the purity and the yield of the dehydroepiandrosterone are improved, the purity of the final product dehydroepiandrosterone is as high as 99%, and the yield is as high as 95%.

The present invention relates to the technical field of biology, and relates to a recombinant strain for producing dehydroepiandrosterone (DHEA), a construction method therefor, and a use thereof. By means of genetically engineered bacteria obtained by reducing or eliminating the enzymatic activity of NAD(P)-dependent oxidase in a starting strain, direct production of DHEA by means of one-step biological fermentation using phytosterol or cholesterol as a substrate can be achieved. By further reducing or eliminating the activity of steroid Δ-isomerase in the genetically engineered bacteria and further reducing or eliminating the activity of oxidoreductase, dehydrogenase and ACP-reductase in a superimposed manner, the yield of DHEA can be accumulated step by step, finally making DHEA become a principal product while reducing the proportions of the by-products 4-AD and androstenediol, thereby improving purity while improving the yield of DHEA, facilitating subsequent treatment and use.

Disclosed herein are compounds and pharmaceutical compositions useful for treating, preventing, reducing, or ameliorating diseases or conditions associated with neurodegenerative disorders. Without being bound by theory, the disclosed compounds and compositions are believed to selectively target tropomyosin receptor kinase A (TrkA) receptor-mediated pro-survival signaling pathways or the nerve growth factor (NGF) or the neurosteroid dehydroepiandrosterone (DHEA) and may prevent, treat, reduce, or ameliorate neurodegeneration.

The invention relates to the technical field of medicine synthesis, in particular to C3 and C20 N-containing pregnane type steroid alkaloid derivatives as well as a preparation method and application thereof. A pregnane type steroid alkaloid skeleton in Miao medicine tri-silver is used as a template, a steroid compound epiandrosterone is used as a raw material, C3-site and C20-site keto compounds are obtained through Wittig alkylenation reaction and oxidation, and the C3-site and C20-site keto compounds are subjected to continuous reductive amination reaction to obtain a series of pregnane type steroid alkaloid derivatives containing N at C3 site and C20 site simultaneously. The C3 and C20 N-containing pregnane type steroid alkaloid derivatives provided by the invention have remarkable anti-inflammatory and anti-gastric ulcer activity, and a scientific basis is provided for searching novel anti-inflammatory and anti-gastric ulcer lead compounds with high selectivity and safety and developing novel anti-inflammatory and anti-gastric ulcer medicines.

The invention discloses a colletotrichum linum P450 enzyme mutant and application thereof, the mutant is obtained by mutating 121st aspartic acid of an amino acid sequence of P450 enzyme CYP68J derived from a colletotrichum linum ST-1 strain into histidine, and the amino acid sequence is shown as SEQ ID NO: 1. Compared with a wild type P450 enzyme, the P450 enzyme mutant disclosed by the invention has the advantages that dehydroepiandrosterone can be efficiently converted into 7 alpha-hydroxy-dehydroepiandrosterone, and the ratio of 7 alpha-hydroxy-dehydroepiandrosterone to 7 alpha, 15 alpha-dihydroxy-dehydroepiandrosterone in a hydroxylation product can be increased from about 4: 5 to about 14: 1; an important way is provided for the biological conversion of the 7alpha-hydroxyl-dehydroepiandrosterone, and the method has important significance on the industrial production of the 7alpha-hydroxyl-dehydroepiandrosterone.

This invention discloses a method for preparing 7α,15α-dihydroxydehydroepiandrosterone (DHEA). The method comprises the following steps: DHEA is fed into a liquid culture medium containing *Colletotrichum lini* to convert the DHEA into 7α,15α-dihydroxydehydroepiandrosterone. The *Colletotrichum lini* liquid culture medium also contains cyclodextrin and its derivatives, and Tween. The conversion step includes: first, a low-temperature conversion, followed by a medium-temperature conversion; the low-temperature conversion conditions are: a conversion temperature of 15–20°C, preferably 16°C; the medium-temperature conversion conditions are: a conversion temperature of 28°C. Furthermore, by adding cyclodextrin and its derivatives and Tween, the feed amount of 7α,15α-dihydroxydehydroepiandrosterone prepared in this invention can be increased from 15 g / L to 30 g / L, and the relative conversion rate can reach 90%.

The present invention relates to a compound suitable for external use and a pharmaceutical composition, the pharmaceutical composition contains 17 beta-dammarin B or a pharmaceutically acceptable salt, a raceme, a stereoisomer, an enantiomer, a diastereoisomer, a tautomer, a metabolite, a solvate and a pro-drug thereof as active ingredients, and the pharmaceutical composition can treat skin cancer or precancerous lesions thereof, such as cancer, cancer, cancer and the like. Especially, the traditional Chinese medicine composition has a good treatment effect on skin squamous cell carcinoma and basal skin cancer.

This invention proposes a method for preparing dehydroepiandrosterone (DHEA), comprising the following steps: S1, dissolving 4-androstenedione in acetic anhydride to obtain a first material, which is then pumped separately into an acetylation microchannel reactor with quaternized GO-phosphotungstic acid catalyst supported on the inner wall for reaction with acetyl chloride; S2, mixing triethyl orthoformate with anhydrous ethanol to obtain a second material, which is then pumped separately into a ketal microchannel reactor with niobium oxide / γ-CD-phosphotungstic acid catalyst supported on the inner wall of the ketal microchannel reactor; S3, dehydrating the effluent from step S2 and adjusting the pH to 7-8, then pumping separately into a reduction microchannel reactor with an ethanol solution containing sodium borohydride for reduction reaction; S4, adding hydrochloric acid to the effluent from step S3 and adjusting the pH to 2-3 to obtain a hydrolysate; evaporating the solvent from the hydrolysate, filtering and drying to obtain DHEA. The supported heteropolyacid composite membrane used in this invention exhibits high catalytic efficiency, high yield, and excellent quality.

The application discloses a kind of structural diversity steroidal ketone derivatives and its chemical-microorganism catalytic combined preparation method and application, belong to biological medicine preparation technical field.The structural diversity steroidal ketone derivatives described in the application include four big types of steroidal derivatives, such as sterol conversion into steroidal ketone derivative, pyrimidine derivative, thiazoline derivative or bis-hydrazone derivative.Firstly, four structural types of sterol derivatives are prepared by chemical method with dehydroepiandrosterone as raw material;Secondly, microbial cell catalysis is used, i.e., new mycobacterium aurum strain is used to catalyze oxidation of sterol and isomerization to obtain novel steroidal ketone derivatives.The chemical-microorganism cell catalytic combined method of the application can realize the preparation of compounds that cannot be obtained by partial chemical method, and the microbial cell catalysis step has mild conditions, simple separation and extraction process, and is environment-friendly, which provides a new strategy for constructing novel steroidal derivative molecular library.

A combination of medications and medication doses is disclosed whereby age-related changes in systemic inflammation, cancer risk, heart disease risk, CD38 expression, hair color, thymotrophic hormones, immune cell populations, the CD4 / CD8 cell ratio, bone marrow density, thymus structure, kidney function, and epigenetic age can be reversed in humans. Surprisingly, agents that accelerate the growth of cells reduce cancer risk, agents that intensify immune responses attenuate age-related inflammation, agents with no prior connection to hair color reverse age-related hair whitening, and a combination of agents that induces IGF-1, a hormone previously thought to drive systemic aging, results in a reversal of systemic aging as documented by an epigenetic clock. Medication combinations useful in the present invention include human growth hormone (GH) or GH releasers, dehydroepiandrosterone (DHEA), and metformin.

The invention belongs to the technical field of chemical synthesis, and particularly relates to an asymmetric synthesis method of an alpha-chiral ester compound. Comprising the following step: in a solvent, performing asymmetric alpha-protonation and esterification reaction on alpha-alkyl-alpha, beta-unsaturated aldehyde and alcohol as shown in a formula II in the presence of a chiral N-heterocyclic carbene catalyst, alkali and protonic acid to obtain the alpha-chiral ester compound. The invention develops a redox esterification reaction based on chiral N-heterocyclic carbene catalysis, so that the redox esterification reaction can be efficiently suitable for various alpha-alkyl alpha, beta-olefine aldehydes from simple to high steric hindrance and from chain to polycyclic; the catalytic strategy can be directly applied to later directional esterification modification of important natural product derivatives such as oestrone and epiandrosterone, and a powerful tool is provided for research and development of new drugs.

The invention provides a method for synthesizing dehydroepiandrosterone through chemical-multienzyme coupling catalysis, and belongs to the technical field of pharmaceutical preparations with specific therapeutic activity. The method comprises the following steps: by taking 4-androstenedione as a substrate, carrying out esterification to synthesize 3-acetoxyandrostane-3, 5-diene-17-ketone; adding a lipolytic enzyme, and catalyzing the 3-acetoxyandrostane-3, 5-diene-17-ketone to synthesize the 5-androstenedione; ketoreductase and glucose dehydrogenase are added, and 5-androstenedione is catalyzed through double-enzyme coupling to synthesize DHEA. The method provided by the invention can realize efficient synthesis of DHEA.

The invention belongs to the field of pharmaceutical compositions, and relates to a composition containing dehydroepiandrosterone, a preparation and a preparation method thereof. The composition containing dehydroepiandrosterone provided by the invention still has stable particle size distribution after standing for 30 days, and is not layered and the particle size distribution is not obviously changed after standing for a long time; after being prepared into a pharmaceutical preparation, the dehydroepiandrosterone derivative has good drug encapsulation efficiency and stable dehydroepiandrosterone content, and has a wide application prospect.

The invention discloses a recombinant keto reductase and application thereof in dehydroepiandrosterone synthesis, the recombinant keto reductase is based on Crocecoccus esterase sourced 3-keto reductase, the recombinant keto reductase is constructed by modifying an active pocket of an enzyme through a genetic engineering technology and computer-aided design, the recombinant keto reductase has outstanding enzymatic activity and stability, and the recombinant keto reductase can be applied to dehydroepiandrosterone synthesis. And a better choice is provided for preparing medicines such as dehydroepiandrosterone and the like by enzyme catalysis keto reduction.

The invention discloses a marker combination for high-salt diet related renal injury from intestinal flora and application. The marker combination is composed of dehydroepiandrosterone and Cyp1a1. The research finds that intestinal flora participates in a related marker combination (namely steroid hormone biosynthesis related metabolite dehydroepiandrosterone and Cyp1a1) of the high-salt diet related renal injury, and ROC curve analysis shows that the biomarkers have good discrimination efficiency in the high-salt diet related renal injury; the effect and application of the gene in the regulation and control of the kidney injury related to the high-salt diet by the intestinal renal axis are verified, and the gene is crucial for early diagnosis, personalized treatment and prognosis evaluation of patients with the kidney injury related to the high-salt diet.

The invention relates to the technical field of synthesis of steroids, in particular to a preparation method of 4-dehydroepiandrosterone. According to the method, 4-AD is taken as a starting material and is subjected to cyaniding, silicon etherification, reduction and hydrolysis reaction in sequence to prepare 4-dehydroepiandrosterone, chlorosilane is used for carrying out silicon etherification protection on hydroxyl in a 4-AD cyano compound, the obtained silicon ether compound can tolerate a sodium borohydride reduction system environment, the content of a reduction byproduct is reduced to 0.5% or below, meanwhile, the selectivity of the reduction reaction is accidentally improved, and the yield of the 4-dehydroepiandrosterone is increased. The total yield reaches 75% or above, the product purity is larger than or equal to 98%, in addition, the production cost is greatly reduced, and the method is suitable for industrial large-scale production.

The application discloses a synthesis method of 5alpha-androsta-2-ene-17-one. The application provides a preparation method of 5alpha-androsta-2-ene-17-one as shown in formula I, and the method is characterized in that the method comprises the following steps: in the presence of a proton base, triphenylphosphine and dimethyl azodicarboxylate (DEAD), androsterone is subjected to an elimination reaction in a solvent to obtain 5alpha-androsta-2-ene-17-one as shown in formula I. The preparation method has the advantages of less isomer impurities, simple post-treatment, cheap raw materials, mild reaction conditions, less damage to the environment and the like, and can be used for industrial production.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a steroidal 1, 2, 3-thiadiazole derivative as well as a synthesis method and application thereof. The derivative has a chemical structure as shown in a formula (I), a formula (II), a formula (III) or a formula (IV). The invention provides a series of brand-new steroidal 1, 2, 3-thiadiazole derivatives for the first time. Besides, the invention further provides a synthesis method of the steroidal 1, 2, 3-thiadiazole derivative, dehydroepiandrosterone is used as a basic raw material, the steroidal 1, 2, 3-thiadiazole derivative is obtained through a series of reactions, the product prepared through the synthesis method is high in yield and easy to separate, and the synthesis method is the optimal method for preparing the steroidal 1, 2, 3-thiadiazole derivative. Bioassay proves that the steroidal 1, 2, 3-thiadiazole derivative provided by the invention shows good poisoning activity on aphids, spider mites and oriental mythimna separata and can be applied to plant pest control.

The present application relates to a kind of P450 enzyme mutant and its application in the preparation of trihydroxy androstene ketone by catalyzing DHEA hydroxylation.The present application provides four kinds of cytochrome P450 enzyme mutants, which are based on wild-type P450 enzyme, the alanine at position 112 is mutated to tyrosine, histidine, lysine and serine respectively by site-directed mutagenesis, which significantly improves the catalytic efficiency, can efficiently catalyze dehydroepiandrosterone (DHEA) to prepare product trihydroxy androstene ketone by two-step hydroxylation reaction.Compared with wild-type cytochrome P450 enzyme, these mutants show excellent catalytic performance, and have important industrial application value in the field of steroid drug synthesis.

The invention belongs to the field of biological medicines, and particularly relates to a method for improving biological synthesis of dehydroepiandrosterone, which comprises the following steps: integrating 17-alpha-hydroxylase / 17, 20 lyase CYP17A1 and reductases POR and CYB5 of the 17-alpha-hydroxylase / 17, 20 lyase CYP17A1 onto a saccharomyces cerevisiae chromosome, establishing a path for synthesizing DHEA (dehydroepiandrosterone), and knocking out alcohol acyltransferase ATF2 to obtain the dehydroepiandrosterone. According to the method, pregnenolone acetate can be reduced to be close to 0, the yield of DHEA is increased by about 50%, and the method has extremely high popularization and application value.

The application discloses a nucleic acid aptamer specifically combined with dehydroepiandrosterone, a kit and application, and comprises a nucleotide sequence shown in SEQ ID No. 1; or a nucleotide sequence with high homology with the nucleotide sequence shown in SEQ ID No. 1 and capable of being specifically combined with dehydroepiandrosterone; or a nucleotide sequence derived from the nucleotide sequence shown in SEQ ID No. 1 and capable of being specifically combined with dehydroepiandrosterone; wherein the primer of dehydroepiandrosterone comprises lib1S1, Lib1A2 and Lib1S1-CS-biotin. The nucleic acid aptamer with high affinity and high specificity is screened, has strong specificity and sensitivity, is a chemical synthetic material, has low use cost and does not have the problem of batch difference in the detection process, and the use of antibody material in the detection process is avoided, so that the detection cost is reduced.