61 results about "Progesterones" patented technology

The invention discloses a progesterone 5beta-reductase mutant and application thereof in synthesis of 5beta-dihydrosteroid, relates to the technical field of biology, and in particular relates to application of gene mining and engineering modification of progesterone 5beta-reductase derived from bacteria in asymmetric synthesis of 5beta-dihydrosteroid. According to the progesterone 5 beta-reductase LpP5beta R disclosed by the invention, the progesterone 5 beta-reductase LpP5beta R from bacteria psoromais is obtained by a gene mining method, and the progesterone 5 beta-reductase LpP5beta R can be subjected to soluble expression in escherichia coli. The mutant obtained by mutating the wild type LpP5beta R has obviously improved catalytic ability on progesterone, and can efficiently catalyze delta 4-3-carbonyl steroids such as hydrocortisone, dinorcitol and the like to generate corresponding 5beta-dihydrosteroids. According to the invention, the technical bottlenecks of poor heterologous expression and low catalytic efficiency of plant-derived progesterone 5beta-reductase are solved, and a potential biocatalyst is provided for green manufacturing of 5beta-dihydrosteroid drugs.

The invention discloses a female-breeding primary pulp composition based on a seed circulation method and a preparation method and application thereof, and relates to the technical field of functional foods.The female-breeding primary pulp composition is prepared from, by weight, 15%-25% of organic flaxseeds, 15%-25% of organic black beans, 10%-20% of figs, 10%-20% of soybeans, 5%-15% of the root of kudzu vine, 5%-15% of pumpkin seeds and 2%-8% of lycium ruthenicum. The invention also provides a preparation method of the female-nourishing protoplasm composition and application of the female-nourishing protoplasm composition in functional food for regulating the balance of female estrogen and progestational hormone. According to the female-nourishing puree composition based on the seed circulation method, various medicinal and edible raw materials are selected and scientifically compounded, a special processing technology is adopted for wall breaking and effect releasing, and the ready-to-drink puree which can be drunk fixedly every day so as to realize synchronous balance adjustment of estrogen and progesterone is prepared; the pain points of high cycle dependence, low absorption rate and inconvenience in use of the traditional method are fundamentally solved.

The application discloses a preparation method of a progesterone vaginal gel, relates to the technical field of gynecological medicine preparation, and realizes the preparation method of the progesterone vaginal gel by using a preparation device of the progesterone vaginal gel. The preparation device of the progesterone vaginal gel comprises a mixing kettle, a top plate is fixedly arranged at the top of the mixing kettle, a driving scraping mechanism is arranged inside the mixing kettle and at the inner side of the top plate, an oil phase preparation mechanism is arranged outside the driving scraping mechanism, a water phase preparation mechanism is arranged at the bottom outside the oil phase preparation mechanism, a premix preparation mechanism is arranged at the top outside the oil phase preparation mechanism, and the top plate and the water phase preparation mechanism are jointly provided with a driving supporting mechanism. The application can effectively shorten the transfer time of the premix and the oil phase, thereby improving the preparation efficiency of the gel product, and the residual oil phase can be recycled, thereby avoiding the waste of the oil phase and guaranteeing the quality of the gel product.

The application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of alpha soludex. The preparation method takes 11-ketoprogesterone as raw material, firstly acetylates the ketone group at the 3 position, then obtains 3beta-hydroxyl through a composite biological enzyme method, and finally obtains alpha soludex through hydrogenation and translocation reaction. The composite biological enzyme method is used to obtain 3beta-hydroxyl, has good specificity, mild reaction conditions, does not need special equipment, and has high conversion efficiency. The preparation method of the application is easy to purify the reaction products of each step, the total mass yield of the final alpha soludex product is greater than 85%, and the HPLC purity is greater than 99.5%. The preparation method of the application has low cost and is suitable for industrial large-scale production.

The invention belongs to the field of pharmaceutical preparations, and provides a medical composition for treating premature delivery and a preparation method thereof. The progesterone nanocrystal (D50 is 250-350 nm) and poloxamer 407 / 188 thermosensitive gel-forming system composite design is adopted, hydroxypropyl methylcellulose or carbomer 974P and a functional adhesion polymer (carbomer-cysteine or carbomer-catechol) are matched, the pH is adjusted to 4.0-4.5 through a lactic acid / sodium lactate buffer system, and the progesterone nanocrystal / poloxamer composite gel-forming agent is prepared. The excellent performance that the sol-gel transition temperature is 30-34 DEG C, the elastic modulus is not smaller than 150 Pa at 37 DEG C, the modulus retention rate is not smaller than 60% after the emulsion is diluted by 5-10 times, the adhesion work is not smaller than 0.60 N.s, and the anti-flushing retention rate is not smaller than 70% after the emulsion is diluted by 5-10 times is achieved. The invention solves the problem of synergy of high-modulus gel strength, rapid self-repairing ability and anti-dilution and anti-flushing stability, realizes unification of long-acting drug release and excellent biological adhesion performance in vagina physiological fluid dilution and mechanical flushing environments, and has wide clinical application value.

The invention provides a cytochrome P450 cholesterol side chain lyase mutant, recombinant saccharomyces cerevisiae for producing progesterone and application of the recombinant saccharomyces cerevisiae. The cytochrome P450 cholesterol side chain lyase mutant is obtained through ESM-2 language model screening, and the catalytic efficiency can be remarkably improved. The efficient recombinant saccharomyces cerevisiae is obtained by constructing the recombinant saccharomyces cerevisiae, optimizing the copy number of key enzymes, introducing an electron transfer system and overexpressing the key enzymes, the yield of progesterone is remarkably increased, and the recombinant saccharomyces cerevisiae is suitable for industrial production of progesterone and has important application value.

This invention belongs to the technical field of steroid compound preparation, specifically relating to a safe post-processing technology for 11α,17α-dihydroxyprogesterone fermentation broth, comprising four processing steps: 1) extraction; 2) saponification; 3) secondary dissolution for impurity removal; and 4) decolorization. This invention employs a four-step post-processing procedure of extraction-saponification-secondary dissolution for impurity removal-decolorization, which not only improves the yield and purity of 11α,17α-dihydroxyprogesterone, achieving a purity of over 99%, but also solves the problem of high-yield extraction of 11α,17α-dihydroxyprogesterone from fermentation broth. Furthermore, it makes the reaction conditions milder, the operation simpler, safer, and more reliable, making it more suitable for large-scale production.

The invention discloses a progesterone enteric-coated tablet processing technology. The technology comprises the following steps: 1, preparing a tablet core; 2, coating an isolating layer; 3, coating an enteric-coated layer; and 4, coloring layer coating. According to the processing technology of the progesterone enteric-coated tablet, the overall technological steps, technological parameters in all the technological steps and the raw material formula are optimized, the steps are simple, operation is easy, the quality of all layers of coatings can be effectively controlled, the stability and consistency of the final product are ensured, the prepared progesterone enteric-coated tablet can stably release medicine in the intestinal tract, and the bioavailability of the product is improved. The absorption speed is high, and the medication comfort and compliance of a patient are improved, so that the requirements of clinical treatment are better met.

The invention provides a chemical synthesis method of 20 alpha-hydroxyprogesterone, and belongs to the technical field of organic synthesis. The invention provides a simple and efficient synthesis path, and high-purity 20 alpha-hydroxyprogesterone can be obtained with good yield and extremely high stereoselectivity and specificity. The method is easy and convenient to operate and good in reproducibility, and effectively overcomes the defects that a product is an isomer mixture, separation and purification are difficult, and the target product yield is low in a traditional method. The successful implementation of the invention provides a stable and reliable material source for obtaining sufficient high-purity 20 alpha-hydroxyprogesterone, powerfully supports the subsequent activity research, dosage form development and new drug creation of the compound, and has important significance in the field of health drugs for women, health protection and health protection. The compound shows important application value and potential in the field of research and development of novel progesterone drugs.

The invention relates to a synthetic method of didrogesterone. According to the method, progesterone is subjected to ketalation, halogenation, elimination, illumination isomerization, deprotection and final isomerization, and the didrogesterone is obtained. The method has the advantages of high yield, cheap and easily available raw materials, green and safe whole process route, high bulk drug quality and purity of 99.8% or more, and is suitable for industrial production.

The invention discloses temperature-sensitive hydroxybutyl polyvinyl alcohol, sustained-release hydrogel and a preparation method and application thereof, and belongs to the field of pharmaceutical preparations. Temperature-sensitive hydroxybutyl polyvinyl alcohol is synthesized by grafting modified polyvinyl alcohol in an alkaline aqueous solution through epoxybutane, no organic solvent is used in the preparation process, and the preparation method is simple, economical and convenient. When the grafting substitution degree of the hydroxybutyl polyvinyl alcohol is 20%-60%, the hydroxybutyl polyvinyl alcohol is dissolved in deionized water or normal saline at a low temperature, progesterone microcrystals are added and uniformly stirred to obtain a drug-loaded gel precursor dispersion liquid, gel transformation is performed in a use environment at a gel transformation temperature or above, and the progesterone vaginal sustained-release hydrogel is formed. The gel is soluble in water at a low temperature, has good fluidity, can be conveniently filled into tissues, and forms gel at a body temperature, and has good tissue mucosa retention. As a progesterone vaginal sustained-release carrier material, the hydrogel disclosed by the invention is expected to be applied to development of products for preventing or treating gynecological diseases or assisting fertility.

The application relates to the technical field of organic synthesis, and particularly discloses a synthesis process of high-purity pregnenolone, which comprises the following steps: S1, esterification reaction of progesterone and an acylation reagent to obtain product 1; S2, ketalization reaction of the product 1, diol and a dehydrating agent in the presence of a catalyst to obtain product 2; S3, reduction reaction of the product 2 and a reducing agent to obtain product 3; and hydrolysis reaction of the product 3 and an acidic compound to obtain pregnenolone. The synthesized pregnenolone has high purity and yield.

The application belongs to the technical field of genetic engineering and enzyme engineering, and discloses a C11 alpha-hydroxylase mutant D118V with improved catalytic activity, wherein the amino acid sequence is shown as SEQ ID NO. 4, and the corresponding nucleotide sequence is shown as SEQ ID NO. 5. The C11 alpha-hydroxylase from Aspergillus ochraceus is subjected to site-directed saturation mutation, and the C11 alpha-hydroxylase mutant D118V for improving the yield of 11 alpha, 17 alpha-dihydroxy progesterone is obtained by using a Saccharomyces cerevisiae expression platform. When the concentration of the substrate 17 alpha-hydroxy progesterone is 2 g / L, the concentration of 11 alpha, 17 alpha-dihydroxy progesterone after 36 h of conversion is 1.19 g / L, and the production intensity is 758.15 mg / (L·d), which is increased by 16.67% and 172.77% compared with the wild-type CYP68J5, thereby providing an application case and basic data support for the modification of steroid C11 alpha-hydroxylase.

The application discloses a steroid C14 alpha hydroxylase CLCYP14 mutant, relates to the field of proteins, and applies a site-directed saturation mutation technology and a combination mutation strategy to screen and obtain CLCYP14 mutants I111L-M115K and I111L-V124W with high hydroxylation specificity. Compared with CLCYP14, the hydroxylation selectivity and conversion rate of I111L-M115K and I111L-V124W for steroid compounds progesterone, 21-hydroxyprogesterone, 5beta-hydroxyprogesterone, 1-dehydroprogesterone, 21-hydroxypregna-1,4-diene-3,20-dione and deoxycortisone are obviously improved.

The invention relates to the technical field of progesterone sustained-release nanoparticle production, in particular to a progesterone sustained-release nanoparticle which comprises progesterone and further comprises solid lipid and liquid lipid according to the formula ratio of 1: 1.4: 1.2: 0.8. A preparation method of the progesterone sustained-release nanoparticle comprises raw material preparation of progesterone, solid lipid and liquid lipid and melt emulsification. The prepared progesterone lipid nanoparticles have high drug entrapment efficiency which can reach 77.48% at most, and have obvious drug sustained and controlled release performance, although the particle size of the nanoparticles is increased along with the increase of the content of liquid lipid-oleic acid in the lipid nanoparticles, the drug entrapment efficiency is improved, the in-vitro release of the drug is accelerated, and the progesterone lipid nanoparticles have good application prospects. According to the progesterone nanostructure lipid carrier, the drug content in the preparation process of the nanoparticles is improved, the drug encapsulation efficiency of the prepared progesterone nanostructure lipid carrier is reduced, but the drug loading capacity of the nanoparticles can be improved, and when the dosage reaches 20%, the drug loading capacity of the nanoparticles can reach 11.57%.

This invention belongs to the field of biotechnology and discloses the application of plant-derived dehydrogenases or their encoding genes in the conversion of progesterone to 6-dehydroprogesterone. The plant-derived dehydrogenase is selected from the steroid 6-position dehydrogenase MtCYP79 derived from *Clematis chinensis* or the steroid 6-position dehydrogenase PsCYP79 derived from *Ligusticum striatum*. It also discloses a genetically engineered *Saccharomyces cerevisiae* strain that produces 6-dehydroprogesterone, which is based on a progesterone-producing *Saccharomyces cerevisiae* starting strain, into which the steroid 6-position dehydrogenase MtCYP79 or the steroid 6-position dehydrogenase PsCYP79 derived from *Ligusticum striatum* is introduced. The resulting genetically engineered *Saccharomyces cerevisiae* strain can produce both progesterone and 6-dehydroprogesterone.

The invention relates to the field of efficient breeding of animals, in particular to a sheep estrus synchronization kit based on follicular wave induction and turnover, application and a use method. The kit contains estradiol benzoate, vitamin ADE, a GnRH analogue buserelin, a progesterone vaginal sustained-release agent, pregnant mare serum gonadotropin and a prostaglandin F2alpha analogue cloprostol sodium according to time nodes, and is matched with instructions for use. According to the method, follicle waves are induced or reset through estrogen and vitamin ADE on the 0th day, buserelin is injected on the 5th day, a progesterone sustained-release agent is placed, follicle development is synchronized, thrombus is removed on the 12th day, PMSG and cloprostenol sodium are jointly injected, follicle final maturation and ovulation are triggered, and estrus testing and mating are conducted 12-96 h after thrombus is removed. According to the scheme, high oestrus rate and highly concentrated oestrus time windows can be obtained for milk goats in different physiological states in the breeding season and the non-breeding season, regular artificial insemination can be conveniently implemented, and the breeding efficiency of a large-scale sheep farm is improved.

The invention relates to the technical field of livestock breeding biology, and discloses a method for promoting porcine ovary granular cell proliferation, which comprises the following steps: adding a porcine follicular fluid exosome into a porcine ovary granular cell culture system, and acting for a certain time at an effective concentration, so as to improve the proliferation activity of granular cells. After the exosome treatment, the apoptosis rate of granular cells can be reduced, the cell survival rate can be improved, and the granular cells can be promoted to secrete steroid hormones, including the estradiol level and the expression of progesterone synthetase. Cell experiments prove that the follicular fluid exosome can effectively improve the activity of granular cells, promote the process of a cell cycle, inhibit cell apoptosis and remarkably enhance the synthesis capacity of steroid hormones such as estradiol and progesterone, and a new intervention strategy is provided for improving follicular development and reproductive performance of sows.

The invention provides a P450 enzyme CYP5103-BM capable of catalyzing 14 alpha-hydroxylation of progesterone, and a mutant CYP5103-BM-Y291H of the P450 enzyme CYP5103-BM. Wherein the gene sequence of the P450 enzyme CYP5103-BM is as shown in SEQ ID NO: 1, and the gene sequence of the mutant CYP5103-BM-Y291H is as shown in SEQ ID NO: 3. The transformants respectively carrying the CYP5103-BM gene and the CYP5103-BM-Y291H gene can be subjected to a whole-cell biological catalytic reaction to convert a substrate progesterone into 14 alpha-hydroxyprogesterone, and the conversion rates in 36 hours respectively reach 50.04% and 88.76%. The mutant CYP5103-BM-Y291H has higher catalytic activity on progesterone, the production cost of 14 alpha-hydroxyprogesterone can be greatly reduced, the production time can be shortened, and the mutant CYP5103-BM-Y291H has extremely high application value for industrial production of progesterone and research of C14-hydroxylated steroid drugs.

The present invention provides a temperature control structure of a reaction equipment, comprising a C-shaped reaction part and a driving part connected between two ends of the reaction part. The driving part and the reaction part form an annular shape, and the reaction part and the driving part defines a reaction cavity; a feeding channel is communicated with the top of the reaction part, a discharging channel is communicated with the bottom of the reaction part, and a control valve is arranged on the discharging channel; driving blades are positioned in the driving part and are used for driving liquid in the reaction cavity to circulate; heat exchange tubes vertically pass through the reaction part, a plurality of heat exchange tubes are vertically arranged on the reaction part, and heat exchange channels vertically pass through the heat exchange tubes; and all the heat exchange tubes are communicated with a medium introduction mechanism. The temperature control structure of the reaction equipment provided by the present invention can improve the reaction efficiency.

The invention discloses a progesterone vaginal sustained-release gel preparation method, which comprises: 1) preparing a polymer phase: dissolving a preservative and a stabilizer in water, stirring to form a colorless transparent liquid, adding carbomer and polycarbophil, and stirring to form a colloidal polymer; 2) preparing an oil phase: mixing glycerol, light liquid paraffin, hydrogenated palm oil glyceride and a stabilizer at a certain temperature to obtain the oil phase; 3) mixing: under an ultrasonic condition, adding the oil phase into the polymer phase, adding progesterone and an opacifying agent under a stirring condition, and stirring to obtain a white milky suspension; and 4) cooling, stirring and homogenizing: vacuumizing, stirring and homogenizing to obtain the progesterone vaginal sustained-release gel. The progesterone vaginal sustained-release gel prepared by the method has good chemical property stability and mixing uniformity.

The invention provides a microbial enzyme catalytic synthesis method of 20 alpha-hydroxyprogesterone, and belongs to the technical field of biosynthesis. The invention establishes an efficient, green and high-selectivity 20 alpha-hydroxyprogesterone biosynthesis method, and the method has the direct effects that the directional hydroxylation of the C20 site of the substrate progesterone is realized by utilizing a recombinase technology, the generation of byproducts is effectively avoided, the subsequent separation and purification process is simplified, the reaction conditions are mild, the cost is low, and the method is suitable for industrial production. The energy consumption and the safety risk are reduced; from the aspect of product application significance, the method provides a stable and reliable material source for large-scale preparation of 20 alpha-hydroxyprogesterone, the environmental protection property and economical efficiency of the production process are remarkably improved, a solid material foundation is laid for in-depth study on the biological activity and application of the compound, and the method is suitable for industrial production. And a beneficial technical reference is provided for green biological manufacturing of other steroid hormone medicines.

The invention discloses a non-alcoholic fatty liver biomarker composition and application thereof, and belongs to the technical field of non-alcoholic fatty liver detection. The non-alcoholic fatty liver biomarker composition comprises at least two of citric acid, linoleic acid, L-glutamic acid, L-glycine, asparaginic acid, progesterone, testosterone and uric acid, and further, the hepatic fibrosis biomarker further comprises at least one of 2-hydroxyestradiol, L-citrulline, L-procholecin, N-acetyl-L-methionine and flavin. The biomarker composition is stable, the possibility of misdiagnosis and missed diagnosis of diseases is greatly reduced, and compared with a single omics analysis method, the biomarker composition is more suitable for the occurrence and development mechanism of the diseases.

The invention provides a progesterone suspension as well as a preparation method and application thereof, and belongs to the technical field of medicines. The preparation method comprises the following steps: dissolving a progesterone raw material medicine in hot vegetable oil, and cooling to separate out progesterone to obtain a progesterone oil suspension; the progesterone oil suspension is mixed with a surfactant, and a progesterone suspension is obtained; or mixing the vegetable oil with a surfactant to obtain a mixed oil phase; dissolving a progesterone raw material medicine in a hot mixed oil phase, and cooling to separate out progesterone, so as to obtain the progesterone suspension, the D90 particle size of progesterone in the progesterone suspension is 4 to 50 [mu] m. The progesterone is dissolved in hot vegetable oil or a mixed oil phase by adopting a hot dissolution and cold separation process, the progesterone can be uniformly separated out and uniformly dispersed in a system through cooling, and the progesterone in the progesterone suspension is uniform in particle size, loose in texture, not easy to agglomerate and relatively good in suspension effect.

This invention discloses sterol side-chain cleaving enzymes and 3β-hydroxysteroid dehydrogenases / Δ from different sources. 4,5 Amino acid sequences, coding sequences, and applications of isomerases. This invention, based on synthetic biology and molecular pharmacognosy, explores sterol side-chain cleaving enzymes and 3β-hydroxysteroid dehydrogenases / Δ from different plant sources. 4,5 Isomerases, which will yield sterol side-chain cleavage enzymes and 3β-hydroxysteroid dehydrogenases / Δ 4,5 The coding sequences of the isomerases were constructed into expression cassettes, and using Saccharomyces cerevisiae as the chassis strain, highly efficient pregnenolone or progesterone synthesizing strains were obtained. The pregnenolone yield of the constructed strains reached as high as 14.46±2.16 mg / L, and the progesterone yield reached as high as 32.78±1.84 mg / L. This achieved high-level synthesis of pregnenolone and progesterone by genetic engineering methods, providing an important foundation for the green synthesis of steroid hormones.

The invention relates to a preparation method of medroxyprogesterone acetate. The preparation method of medroxyprogesterone acetate comprises the following steps: mixing 17alpha-hydroxyprogesterone with glacial acetic acid, acetic anhydride and a first catalyst for first reaction to prepare an intermediate 1; mixing the intermediate 1 with tetrahydrofuran, ethanol, triethyl orthoformate and a second catalyst to carry out a second reaction, then adding formaldehyde and N-methylaniline to carry out a third reaction, then adding hydrochloric acid and water to carry out a fourth reaction, and collecting a crude product of an intermediate 2; and preparing the medroxyprogesterone acetate through a series of refining steps. According to the preparation method, the dosage of the palladium-carbon catalyst is small, the cost can be obviously reduced, and the product is lower in impurity content and higher in purity.

The invention provides a compound estradiol-progesterone transdermal patch and a preparation method thereof, and belongs to the technical field of medicines. The compound estradiol-progesterone transdermal patch provided by the invention comprises a backing layer, a drug-containing pressure-sensitive adhesive layer and a protective layer, and the drug-containing pressure-sensitive adhesive layer is located between the backing layer and the protective layer; the drug-containing pressure-sensitive adhesive layer comprises estradiol, progesterone, a penetration enhancer, a plasticizer, an antioxidant and a pressure-sensitive adhesive. The compound estradiol-progesterone transdermal patch provided by the invention is good in formability and adhesiveness, and a transdermal penetration test and pharmacokinetics show that the compound estradiol-progesterone transdermal patch provided by the invention is good in transdermal performance, and has an obvious slow release characteristic in in-vivo and in-vitro drug release.

This invention relates to the field of progesterone preparation technology, specifically to a progesterone lipid liquid crystal suitable for injection, its preparation method, and the pharmaceutical uses of the product. The progesterone lipid liquid crystal injection provided by this invention is a lipid liquid crystal system formed by mixing an oil phase and an aqueous phase. The oil phase includes progesterone, benzyl benzoate, phospholipids, vitamin E, and oleic acid, while the aqueous phase includes water for injection. This invention optimizes the mass ratio of phospholipids to oleic acid in the oil phase to 10:1, and the mass ratio of progesterone, benzyl benzoate, and vitamin E to 2:6:(5-3), resulting in a stable lipid liquid crystal system that improves injection compliance, reduces fat deposition, and achieves sustained drug efficacy for more than 12 hours.

The invention relates to the technical field of organic synthesis, and particularly discloses a synthesis process of high-purity pregnenolone, which comprises the following steps: S1, carrying out esterification reaction on progesterone and an acylation reagent to obtain a product 1; s2, the product 1, diol and a dehydrating agent are subjected to a ketalation reaction in the presence of a catalyst, and a product 2 is obtained; s3, carrying out reduction reaction on the product 2 and a reducing agent to obtain a product 3; and carrying out hydrolysis reaction on the product 3 and an acidic compound to obtain pregnenolone. According to the present invention, the synthesized pregnenolone has high purity and high yield.