35 results about "Progesterones" patented technology

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 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 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.

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 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.

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.

1. The name of the design product: packing box (progestin soft capsule). 2. The use of the design product: the design product is used for packing of goods. 3. The design points of the design product: the combination of shape and pattern. 4. The picture or photo that best shows the design points: perspective view.

This invention relates to the field of biotechnology, and more particularly to a P450 enzyme mutant for steroid C11α-hydroxylation, the amino acid sequence of which is shown in SEQ ID NO:2. In a whole-cell catalytic system of *Saccharomyces cerevisiae*, this P450 enzyme mutant achieved a 14-fold increase in the conversion rate of 17α-hydroxyprogesterone compared to the wild type. Expression of this mutant in a systematically modified *Pichia pastoris* chassis strain increased the substrate conversion rate to 96.5% and the product selectivity to 99.1%. Scale-up culture at 2.5 L, with a single feed of 60 g of substrate, yielded a 11α,17α-dihydroxyprogesterone titer of 24.8 g / L. Furthermore, this mutant also exhibited good catalytic activity and C11α-hydroxylation selectivity for various steroid drugs such as progesterone and canrenone, demonstrating a broad substrate spectrum and promising prospects for industrial applications.

The invention discloses a progesterone long-acting slow-release injection as well as a preparation method and medical application thereof. The progesterone long-acting slow-release injection comprises a therapeutically effective amount of progesterone, a pharmaceutically acceptable ester organic solvent; the solvent is selected from the combination of glyceryl triacetate and benzyl benzoate. The progesterone long-acting slow-release injection provided by the invention can form a drug reservoir in situ after injection, realizes long-term slow release of progesterone, remarkably reduces the initial burst release effect, and can be used for treating or preventing luteal insufficiency or luteal support in assisted reproduction. In addition, the progesterone long-acting slow-release injection is simple in preparation process, all the components can be dissolved and mixed at the room temperature, and large-scale production is easy to achieve.

The invention discloses a purification method of a progesterone crude product, and belongs to the technical field of purification of organic compounds. The purification method of the progesterone crude product comprises the following steps: adding acid into a progesterone crude product reaction solution, dropwise adding a sodium hypochlorite solution at 0-30 DEG C for reaction, quenching, separating liquid, washing an organic phase with a sodium hydroxide solution after liquid separation, and concentrating a water precipitation material under reduced pressure by the organic phase to obtain purified progesterone. According to the method, the impurity I and the impurity L are efficiently removed under the mild reaction condition.

The present application provides a kind of transvaginal, rectal administration progesterone sustained-release solid composition. Specifically, the composition includes: progesterone 100 parts by weight, cyclodextrin 800-2000 parts by weight, filler 10-30 parts by weight, binder 20-40 parts by weight, optionally preservative 0.5-10 parts by weight, polyoxyethylene 30-300 parts by weight and lubricant 4-30 parts by weight. The composition of the present application is based on progesterone-cyclodextrin inclusion and polyoxyethylene sustained-release synergistic effect for preparing vaginal, rectal administration preparation, not only has the physical properties suitable for vaginal, rectal administration (such as adhesion performance, prevent the preparation from sliding), but also can ensure that progesterone is stably released in vagina for a long time, improve bioavailability, reduce the side effects of progesterone administration.

The invention discloses application of a late pregnancy urine metabolism marker of gestational diabetes mellitus and a kit, and provides application of the late pregnancy urine metabolism marker of gestational diabetes mellitus in preparation of related drugs for prevention and / or treatment of gestational diabetes mellitus. According to the invention, three urine metabolism markers in late pregnancy, which are obviously associated with the occurrence risk of gestational diabetes mellitus, are obtained through screening, the expression of 17alpha-hydroxyprogesterone and alcadipine is up-regulated, the expression of 7-methyluric acid is down-regulated, and the three urine metabolism markers can be used as detection targets for early prediction of gestational diabetes mellitus, and can be used for early prediction of gestational diabetes mellitus. Or the compound can be used as a target for research and development of related drugs for preventing and treating gestational diabetes mellitus.

The invention relates to the technical field of veterinary drugs, in particular to a high-stability progesterone injection and a preparation method thereof. The progesterone injection is prepared from the following components: 8 to 12 mg / ml of progesterone, 0.8 to 1.2 mg / ml of vitamin E and oil for injection. The progesterone injection is prepared by the following steps: taking oil for injection, adding vitamin E, heating in a water bath, stirring for 10-15 minutes, then adding progesterone, supplementing the oil for injection, stirring for 15-20 minutes, and introducing nitrogen for protection in the whole process to obtain the high-water-solubility florfenicol powder and a semi-finished product of the progesterone injection. And filtering, filling, sealing and sterilizing the semi-finished product progesterone injection to obtain the high-stability progesterone injection. Through the antioxidant design of solvent-antioxidant-inert gas, oxidation and hydrolysis paths are remarkably inhibited, high stability of the injection is achieved, safety and compliance are both achieved, and the progesterone injection is superior to a traditional progesterone injection which is not added with an antioxidant or only depends on single protection.

The invention discloses a finasteride intermediate as well as a preparation method and application thereof, and belongs to the technical field of medicine synthesis. The preparation method of the finasteride intermediate comprises the following steps: mixing progesterone and an organic solvent, continuously introducing ozone at-20 DEG C to-10 DEG C to obtain an intermediate state I, dropwise adding peroxide at-10 DEG C or below, dropwise adding a sodium hydroxide solution, heating to 15-25 DEG C, and reacting to obtain the finasteride intermediate. In addition, the invention also provides the finasteride intermediate which is prepared by the preparation method. In addition, the invention also provides an application of the finasteride intermediate in preparation of finasteride. According to the method, sodium periodate does not need to be used, 4-position double bonds can be cut off through oxidation by adding a small amount of peroxide and a sodium hydroxide solution, the finasteride intermediate is obtained, and the green chemical requirement is met.

The invention discloses a progesterone vaginal sustained-release gel composition and a preparation method, the progesterone vaginal sustained-release gel composition comprises progesterone, carbomer, polycarbophil, sorbic acid, stearin, glycerin, light liquid paraffin, sodium hydroxide and purified water, carbomer and polycarbophil are gel substrates, and light liquid paraffin and stearin are oil phases. The progesterone vaginal sustained-release gel disclosed by the invention is uniform in raw material dispersion, stable in quality, low in finished product impurity level and good in safety.