35 results about "Calcitriol" patented technology

The invention discloses a C1, 25-bit dihydroxylase mutant of vitamin D3 as well as a genetically engineered bacterium and application thereof, and belongs to the technical field of enzyme engineering. The preparation method comprises the following steps: mutating 81-site glutamic acid of vitamin D3 dihydroxylase of bacillus megatherium H-1 into alanine to obtain a vitamin D3 dihydroxylase mutant; pMA5 is used as an expression plasmid to realize heterologous expression of the vitamin D3 dihydroxylase mutant in the bacillus subtilis; when the engineering bacteria disclosed by the invention are applied to calcitriol synthesis, the mutant has the effects of increasing the concentration accumulation amount of a product and shortening the reaction time consumption, and the production requirements of shortening the time cost in industrial production are met.

The invention provides an efficient and stable calcitriol soft capsule and a preparation method thereof, and relates to the technical field of pharmaceutical preparations, the efficient and stable calcitriol soft capsule comprises a content and a capsule wall, the content is prepared from olive oil, algal oil, calcitriol, vitamin E, an antioxidant and carboxymethyl guar gum-chitosan liquid, the capsule wall is prepared from glycerol and xanthan gum; the preparation method comprises the following steps: dropping the content and the capsule wall by using a pill dropping machine, cooling in liquid paraffin, collecting condensed capsules, blowing out air, shaping and drying, washing, drying and screening to obtain the efficient and stable calcitriol soft capsule.

A single unit oral dose pharmaceutical composition for use as a medicament for separate, sequential or simultaneous administration with an agonist of a 5-hydroxytryptamine (5-HT) receptor;wherein the single unit oral dose pharmaceutical composition comprises a first active ingredient and a second active ingredient;wherein the first active ingredient is for absorption in the gastrointestinal tract from the oesophagus onwards and the second active ingredient is for absorption in the oral cavity; andwherein the first active ingredient is naltrexone in an amount of 0.01 to 10 mg and the second active ingredient is calcitriol in an amount of 80 to 200 ug.

The invention discloses a method for constructing a zebrafish osteoporosis model by using levothyroxine sodium, and belongs to the field of biological medicines. An existing zebrafish osteoporosis model has the problems of high toxicity, poor specificity and the like, and is solved through the following steps that 5 dpf normally-developed wild type AB line zebrafish juvenile fish is selected, a levothyroxine sodium E3 culture medium with the concentration of 7.81-250 mg / mL is used for continuous treatment from 5 dpf to 8 dpf, the model is verified by detecting the vertebra fluorescence area, brightness and number, and the zebrafish osteoporosis model is obtained. The toxicity is evaluated by combining indexes such as body weight and body length. The result shows that the vertebra mineralization of the model is obviously reduced, and the phenotype can be obviously reversed by the positive drug calcitriol. The model provided by the invention has the characteristics of strong skeleton specificity, low toxicity and reversibility, and is suitable for osteoporosis mechanism research and drug screening.

The invention discloses a calcitriol impurity B and a preparation method thereof, and belongs to the technical field of medicines. The preparation method of the calcitriol impurity B comprises the following steps: S1, mixing an intermediate 3, a first solvent and alkali, and then heating for reflux reaction to obtain an intermediate 4; and S2, dissolving the intermediate 4 in a second solvent, cooling to 0-5 DEG C, adding a photosensitizer, and reacting under the illumination condition to obtain the calcitriol impurity B. The calcitriol impurity B prepared by the preparation method provided by the invention is high in yield, and the purity of the product can reach 99% or above.

This invention relates to a formulation comprising a combination of sodium pentaborate pentahydrate and calcitriol, the active form of vitamin D, which shows anti-cancer effect when used in the treatment of hepatocellular carcinoma. The object of the invention is to provide an anti-cancer effect against hepatocellular carcinoma by a formulation obtained from the combination of sodium pentaborate pentahydrate and calcitriol.

The invention discloses a bone marrow mesenchymal stem cell osteogenesis induction enhancing solution, which is prepared from the following components: 6.5 to 9.5 mg / ml of sodium hydrosulfite, 8.5 to 13.5 mg / ml of nicotinamide ribose, 1.5 to 2.1 mg / ml of deoxycholic acid, 45.0 to 55.0 mu g / ml of estradiol, 0.2 to 0.6 mg / ml of calcitriol, and 90.0 to 110.0 mu g / ml of rrBMP-2. Traditional osteogenic induction and 1% osteogenic induction enhancing liquid have high cell activity on BMSC cell proliferation, and compared with traditional osteogenic induction (containing 0.2 mmol / L of ascorbic acid, 10 mmol / L of beta-sodium glycerophosphate and 100 nmol / L of dexamethasone), the alkaline phosphatase staining color is deeper, the positive area is larger, the alkaline phosphatase activity is higher, more calcium nodules are formed, and the BMSC cell proliferation effect is better. It is shown that the osteogenic induction enhancing liquid provided by the invention enhances the osteogenic ability of the rat BMSC.

This invention provides ACE2 expression inhibitors and their application in ACE2-mediated diseases. It uses human RXRα as a target protein for virtual drug screening and employs computer molecular docking technology to screen compounds with high affinity for the human RXRα receptor. Combined with cell experiments, it screens compounds that inhibit ACE2. The ACE2 expression inhibitors are at least one of ten drugs selected from ursolic acid, phlorizin, resveratrol, triamcinolone, budesonide, fluticasone propionate, vitamin D2, vitamin D3, calcitriol, and alfacalcidol. The ACE2 inhibitors screened by this invention can serve as targeted drugs for ACE2-mediated diseases, providing more drug options for the prevention or treatment of these diseases.

The invention provides a synthesis method of an intermediate for preparing a fluorocalcitriol 23, 24-double bond derivative, and relates to the field of organic chemistry, beta unsaturated acid ester is used as a trans-double bond side chain donor reagent and is subjected to a coupling reaction with an upstream substrate to obtain a beta trans-double bond terminal ester group compound, the technical prejudice is broken through, and the yield of the intermediate is improved. A target product is obtained with high selectivity, the yield can reach 92%, the technical problem of synthesis of a terminal ester compound with beta trans-double bonds is solved, the terminal ester compound with beta trans-double bonds is reacted to generate a final CD ring intermediate with 23 and 24-double bonds, and a process route of the CD ring intermediate with 23 and 24-double bonds is broken through, so that the fluorine calcitriol 23, 24-double bonds are synthesized, and the yield of the fluorine calcitriol 23, 24-double bonds is increased. According to the invention, a key intermediate is provided for a 2, 4-difluoro-1, 4, 24-double bond derivative, a material basis is provided for the provision of a fluorocalcitriol impurity reference substance and the discovery of a bone metabolism drug, and the economic cost is reduced.

The invention discloses a preparation and preparation method of a soft capsule for improving the absorption of an osteoporosis medicine, and the soft capsule for improving the absorption of the osteoporosis medicine comprises the following main components: a medicine absorption component, a bone health promoting component and a capsule forming component, the drug absorption component is composed of vitamin D3, calcitriol, alfacalcidol, an emulsifier and a stabilizer. The vitamin D3, calcitriol, alfacalcidol, the emulsifying agent and the stabilizing agent are arranged, medicine absorption can be enhanced, it is ensured that internal medicine is fully absorbed, and calcium molecules, phosphorus molecules, collagen, vitamin D2, magnesium molecules, zinc molecules, vitamin K, chondroitin sulfate and milk mineral salt are arranged, so that the content of the calcium molecules, the phosphorus molecules, the collagen, the vitamin D2, the magnesium molecules, the zinc molecules, the vitamin K, the chondroitin sulfate and the milk mineral salt is improved. The bone rehabilitation of a patient can be enhanced again, the rehabilitation rate of the patient is increased, the quality of the capsule can be safer by arranging gelatin, glycerin and water, and the problems that the preparation process is too tedious and the improvement effect of the capsule is insufficient are solved.

The invention discloses a preparation method of a fluorine bone triol intermediate, which comprises the following steps: (20S)-3beta-acetoxy-20-methyl-21-iodo-pregna-5-ene as shown in a formula II is taken as a raw material, and 26, 26, 26, 27, 27, 27-hexafluoro-25-hydroxycholesterol is prepared through four steps of reaction, namely coupling, ester hydrolysis, trifluoromethyl substitution and trifluoromethyl addition, and the reaction formula is as shown in the specification. The method has the advantages of simple process, cheap and easily available reagents, and suitableness for industrial production.

Compositions and methods for treating or preventing obesity are provided. The compositions use compounds which act as vitamin D receptor agonists / activators (VDRA), preferably Vit D or calcitriol analogs or derivatives. The disclosed compositions can administered to a subject in need thereof, to treat on or more symptoms of obesity. The compounds can be used to promote a healthy body composition and to avoid the risks associated with overweight and / or obesity, such as cardiovascular disease cancers, urinary incontinence, diabetes and the like. The disclosed compositions can also be used prophylactically to treat animals that are overweight with a risk of becoming obese or animals that are at risk of becoming overweight and are on a high fat diet.

The application discloses a kind of calcitriol soft capsule content in vitro evaluation method and its application, belong to the technical field of pharmaceutical analysis.The method uses diffusion cell device, under certain conditions, the dissolution and penetration behavior of calcitriol soft capsule content is simulated and determined.Specifically, acidic or buffered salt medium solution containing specific proportion alcohol is added to diffusion cell, so that liquid surface is flush with filter membrane;The sample to be measured content is placed above filter membrane;At specified temperature, rotation speed, sample is taken from the lower part of diffusion cell at different time points, and the concentration of calcitriol is determined.The method of the application can accurately and conveniently evaluate the in vitro release behavior of calcitriol soft capsule content prepared by different prescriptions or processes, has high correlation degree with in vivo effectiveness, and has good repeatability, to provide reliable in vitro evaluation tool for product quality control and prescription screening.

The present invention discloses a genetically engineered bacterium, which is an engineered bacterium constructed by expressing CYP gene, ferredoxin gene, ferredoxin reductase gene and dehydrogenase gene in cells; wherein, the amino acid sequence encoded by the CYP gene is as shown in SEQ ID NO.1, SEQ ID NO.3, SEQ ID NO.9 or SEQ ID NO.11. The present invention also discloses the application of the genetically engineered bacterium in the preparation of calcifediol and / or calcitriol. When the engineered bacterium of the present invention is applied to the synthesis of calcifediol and calcitriol, the yields are significantly improved. When it is applied to industrial production, the cost is lower, and the reaction has high specificity, mild reaction conditions and environmental friendliness, meeting the industrial production requirements of calcifediol and calcitriol.

The invention provides a sustained-release fluorocalcitriol tablet and a preparation method thereof, and relates to the technical field of pharmaceutical preparations, the preparation raw materials comprise a sustained-release skeleton layer prepared from a fluorocalcitriol-containing drug core particle and a controlled-release film coating solution containing a methacrylate copolymer, the preparation method comprises the following steps: preparing the medicine core, preparing the controlled-release film coating solution and coating, preparing the controlled-release skeleton layer, and drying and packaging.

The present invention provides a fusion protein or a variant thereof, which includes K1 and RhFR, wherein the amino acid sequence of the K1 is shown in SEQ ID NO:1, and the amino acid sequence of the RhFR is shown in the amino acids at positions 466-773 of SEQ ID NO:5. The present invention also provides a preparation method and application of the fusion protein or a variant thereof. When the fusion protein or a variant thereof of the present invention is applied to catalyze VD3 to synthesize 25-hydroxyvitamin D3 (calcifediol), no additional electron transfer-related protein needs to be added, the operation is simple, and the electron transfer efficiency and catalytic efficiency in the fusion protein are high, the yield of the obtained calcifediol is significantly improved, and the production cost is reduced, which is suitable for industrial production.

The present invention belongs to the technical field of drug analysis, and specifically relates to a method for separating and detecting calcitriol starting material B1 and its impurities. The impurities include impurities B 1a 、Impurity B 1b 、Impurity B 1c One or more of. The self-built high performance liquid chromatography method of the present invention is used for the separation and detection of the calcitriol starting material B1 and its impurities. The chromatographic column uses silica gel covalently bonded to cellulose tris (3,5-dimethylphenylcarbamate) as a filler, and a mixed solution of n-hexane, tert-butyl methyl ether and methanol as a mobile phase for isocratic elution; then enters the detector for detection, and the main component self-control method is used to calculate the content of each impurity according to the measured chromatogram. The method has the characteristics of good separation, good durability, high sensitivity and good reproducibility.

The invention discloses the application of the Chinese wolfberry fruit-glossy privet fruit and calcitriol composition in the medicine for treating postmenopausal osteoporosis for the first time, and through three-layer research of'in vitro cell-animal model-molecular pathway ', it is clear that the composition can bidirectionally regulate and control kidney vitamin D metabolic enzyme by activating'PI3K-AKT' signal pathway for the first time, so that the curative effect on postmenopausal osteoporosis is achieved. Further, the serum 25 hydroxyl vitamin D and blood calcium level are improved, and the bone mineral density is improved. The mechanism provides a modern molecular biology support for the traditional Chinese medicine theory of'kidney dominating bone ', and also establishes a new path of'regulating kidney metabolic enzyme to treat osteoporosis'. By optimizing the metabolic bone protection effect of the vitamin D, bone loss of ovariectomized mice is effectively delayed, meanwhile, the vitamin D and calcitriol play a synergistic effect, and the vitamin D has a multi-target bone protection effect in postmenopausal PMOP, has anti-osteoporosis activity and can be used for treating the PMOP.

Disclosed are methods for the treatment of peripheral neuropathic pain disorders associated with keratin dysregulation via localized, topical administration of calcitriol and / or calcitriol analogues. Such keratin-related peripheral neuropathic pain disorders include pachyonychia congenita, Olmsted syndrome, and other disorders involving palmoplantar keratoderma (PPK). A topical treatment composition including a therapeutic amount of calcitriol or an analogue such as cholecalciferol can provide analgesic effects and / or can reduce excessive keratinocyte proliferation.

A method for determining a dissolution curve of a calcitriol soft capsule comprises the following steps: step 1, taking the calcitriol soft capsule, according to a dissolution rate determination method, using a phosphate buffer solution containing a surfactant as a dissolution medium, operating according to the method, taking a dissolution solution, filtering, taking a subsequent filtrate, adding a stabilizer, and uniformly mixing to obtain a test solution; 2, diluting a proper amount of calcitriol reference substance into a reference substance stock solution by using a mobile phase, taking a proper amount of the stock solution, and diluting the stock solution into a reference substance solution by using a phosphate buffer solution containing a surfactant and a stabilizer as a diluent; 3, detecting by liquid chromatography mass spectrometry to obtain chromatograms of the test solution and the reference solution, and quantitatively determining the dissolution amount of calcitriol by an external standard method; by investigating the type and concentration of an active agent, different chromatographic columns, the type and concentration of a stabilizer, selection of mass spectrum parameters and the like, the detection sensitivity, specificity and stability are effectively improved, and the dissolution curve of the calcitriol soft capsule can be effectively detected.

The invention discloses a medicine for treating anxiety and depression symptoms, which comprises calcitriol, and also discloses an application of the medicine for treating anxiety and depression symptoms in construction of an anxiety and depression symptom model. According to the medicine for treating anxiety and depressive symptoms and the application thereof, mice with anxiety and depressive symptoms are intervened with nasal drop calcitriol, animal experiment evidences are provided for supplementing calcitriol to intervene autism spectrum disorders in the early stage of clinical experiments, and a new thought is provided for early prevention and treatment of neurodevelopment disorders of clinical children.

The invention discloses a method for synthesizing calcitriol (1 alpha, 25-dihydroxy vitamin D3) through biological fermentation of pichia guilliermondii GXDK6 and application of the calcitriol, and belongs to the field of microbial fermentation and biological pharmacy. According to the present invention, the microorganism Pichia guilliermondii GXDK6 is adopted as the starting strain, the cheap carbon source and the conventional culture medium component are adopted as the fermentation substrate, the fermentation is performed for 16-120 h under the fermentation process conditions that the fermentation system is 100-5000 mL, the inoculation amount is 0.5-5.0%, the temperature is 30-37 DEG C, the pH value is 4.0-10.0, and the stirring rotation speed is 0-300 rpm, and the concentration of the biosynthesized calcitriol achieves 0-20.85 mg / L. The method for synthesizing calcitriol through biological fermentation by using Pichia guilliermondii GXDK6 can effectively solve the problems of high cost, complex process, great environmental harm, limited material source, long production period and the like in the traditional method for producing calcitriol, and belongs to a novel method for obtaining calcitriol. The method has an important potential value in the aspects of mass production and application of calcitriol.

The invention belongs to the field of calcitriol capsules, and particularly relates to a calcitriol capsule and a preparation method thereof. In order to avoid the use of a cosolvent, increase the safety of a calcitriol soft capsule, simplify the production process and assist dissolution with room-temperature ultrasound in the liquid preparation process, the invention provides a calcitriol capsule, the content of the calcitriol capsule comprises calcitriol, an antioxidant and a solvent, the solvent is medium-chain triglyceride, the content does not contain ethanol, and the antioxidant is a calcium stearate. The antioxidant is selected from one or a combination of hydroxyanisole and butylated hydroxytoluene. Compared with a commercially available preparation, the preparation has the technical effects that a cosolvent-ethanol in a prescription is removed, and the safety of a product is improved; the production process is optimized, the preparation loss is reduced, and the product quality and stability are improved.

The invention discloses application of vitamin D in preparation of a protection medicine for avoiding ovarian injury caused by chemotherapy, and belongs to the technical field of biology. It is found for the first time that in an experiment of intraperitoneal injection of calcitriol (the active form of vitamin D) and retinoic acid in newborn mice, DNA damage caused by chemotherapeutic drugs cyclophosphamide and adriamycin can be partially reversed when calcitriol and retinoic acid are independently used; the number of primordial follicle apoptosis caused by chemotherapeutic drugs (including cyclophosphamide and adriamycin) is remarkably reduced, and the effect of combined medication (calcitriol and retinoic acid) is better. The discovery expands the application of vitamins in the female reproductive system, provides a new thought for preventing ovarian follicle development from being damaged by chemotherapy drugs and in-vivo protection of fertility, and also has important significance for protecting the life quality of female patients after chemotherapy.

The present invention refers to food compositions comprising selenium, preferably in an amount of at least 4 μg / g, and a set of different ingredients selected from retinyl palmitate, calcitriol (1,25(OH)2 Vitamin D3), phylloquinone (phytomenadione, Vitamin K1), tocopherol (preferably a-tocopherol), or ubiquinol. The invention particularly refers to chocolate bars comprising selenium and the set of different ingredients. Consumption of the food compositions of the invention can reverse, reduce or slow signs of aging in a subject. The invention also relates to methods of producing cacao fruits, cacao beans, cacao mass, and cacao powder with an increased selenium content.

The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a method for separating and determining calcitriol intermediate Z2 and impurity DMP. According to the method, the calcitriol intermediate Z2 and the impurity DMP are separated and measured by adopting high performance liquid chromatography, an AQ column with octadecylsilane chemically bonded silica as a filler is adopted as a chromatographic column, a phosphoric acid aqueous solution is adopted as a mobile phase A, an organic solvent is adopted as a mobile phase B, and the calcitriol intermediate Z2 and the impurity DMP are separated through linear gradient elution. Then detecting in a detector to obtain a chromatogram; and finally quantifying by adopting a limit method. According to the method, the impurity DMP in the calcitriol intermediate Z2 is effectively separated and measured, effective control over the impurity is achieved, the product quality is fundamentally determined, and the method has the advantages of being simple, convenient, rapid, high in specificity, high in sensitivity and high in accuracy.

1. Name of the product in this design: Packaging Box (Calcitriol Soft Capsules). 2. Intended use of this design: pharmaceutical packaging. 3. The key design features of this product are the combination of shape and pattern. 4. The image or photograph that best illustrates the design's key points: a 3D model.

Provide improved means for transdermally delivering a pesticidal or other toxic agent from a composition containing the toxic agent to a target animal, particularly into its bloodstream. **Solution**: A composition for killing animals, such as rodents, comprising (i) one or more toxic agents toxic to the animal, such as cholecalciferol or 25-hydroxy cholecalciferol (vitamin D3), as a toxic component, and (ii) a carrier system for the toxic component, wherein the carrier system (ii) comprises (a) at least one solvent or dispersion medium for the toxic component, such as an alcohol like ethanol, and (b) at least one skin disrupting component, such as dimethyl sulfoxide (DMSO). The composition enhances the skin penetration of the toxicant into or through the skin of the animal where the composition is sprayed or delivered, for example, in a trap or other device. ​

According to the calcitriol injection and the preparation method, in the method, the oxygen content of a liquid preparation container, the oxygen content of injection water and the oxygen content in the filtering process are strictly controlled, and calcitriol is prevented from being degraded in the presence of oxygen; dissolution of calcitriol, mixing with water for injection and filtration are carried out under the condition that the illumination intensity is lower than 200Lux, so that the influence of illumination on calcitriol is avoided; meanwhile, by controlling the mixing temperature of the preparation raw materials and adjusting the pH value of the liquid medicine, the influence of the pH value and the temperature on calcitriol can be effectively avoided, the drug stability of calcitriol is improved, and a high-temperature sterilization process is tolerated.