27 results about "Calcitriol" patented technology

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.

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 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 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 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.

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. ​

Use of vitamin D in the preparation of a protective drug for avoiding chemotherapy-induced ovarian injury, pertaining to the field of biotechnology. It has been discovered for the first time that in experiments involving intraperitoneal injection of calcitriol (the active form of vitamin D) and retinoic acid into newborn mice, both calcitriol and retinoic acid, when used individually, can partially reverse the DNA damage caused by the chemotherapeutic drugs cyclophosphamide and doxorubicin, and significantly reduce the number of primordial follicle apoptosis induced by chemotherapeutic drugs (including cyclophosphamide and doxorubicin); the combined drug use (calcitriol + retinoic acid) has a better effect. This discovery expands the application of vitamins in the female reproductive system, provides new ideas for preventing damage to ovarian follicle development caused by chemotherapeutic drugs and for the in vivo protection of fertility, and is also of great significance for safeguarding the quality of life of female patients after chemotherapy.

The present invention relates to a formulation comprising a combination of sodium pentaborate pentahydrate and calcitriol (active form of vitamin D), which exerts an anti-cancer effect in the treatment of hepatocellular carcinoma. The purpose of the present invention is to provide an anti-cancer effect on hepatocellular carcinoma by a preparation obtained from a combination of sodium pentaborate pentahydrate and calcitriol.

The invention belongs to the technical field of cancer treatment, and discloses a method for inducing mitochondrial apoptosis and remodeling an immunosuppressive tumor microenvironment to inhibit CRPC by targeting DHCR7 and cooperating with enzalutamide. It is found that drug-resistant cells show remarkable cholesterol accumulation and cholesterol ester reduction, meanwhile, 7-DHC depletion is accompanied, the level of 7-DHC can be recovered through drug treatment, mitochondrial damage dependent on reactive oxygen species (ROS) is caused, and tumors are sensitive to enzalutamide again. Calcitriol and enzalutamide act synergistically to overcome drug resistance and activate anti-tumor immunity, associating epidemiological observations about the association between vitamin D deficiency and invasive prostate cancer over tens of years with viable treatment strategies. The results not only expand the understanding of metabolic heterogeneity in castration resistant prostate cancer (CRPC), but also provide a biomarker-based framework for using existing therapies to resist fatal treatment drug resistance.

The application discloses a C1, 25-position double-hydroxylase mutant of vitamin D3 and a genetically engineered bacterium and application thereof, and belongs to the technical field of enzyme engineering. In the application, the glutamic acid at position 81 of vitamin D3 double-hydroxylase of Bacillus megaterium H-1 is mutated into alanine to obtain a vitamin D3 double-hydroxylase mutant; pMA5 is used as an expression plasmid to realize heterologous expression of the vitamin D3 double-hydroxylase mutant in Bacillus subtilis; and the application of the engineered bacterium of the application to the synthesis of calcitriol has the effects of improving the product concentration accumulation amount and shortening the reaction time consumption, and meets the production demand of shortening the time cost in industrial production.

The invention discloses a calcitriol composition for treating hypocalcemia of patients suffering from chronic renal dialysis and a preparation method of the calcitriol composition. The composition consists of the following components: calcitriol, a solubilizer, an antioxidant, buffer salt, glycerol, a proper amount of a pH regulator and water for injection. The preparation method of the calcitriol injection comprises the following steps: preparing the raw and auxiliary material components in batches, adding calcitriol into a mixture of the solubilizer and the glycerol, stirring and dissolving uniformly, mixing the mixed solution of the three components with the antioxidant and the buffer saline solution, adjusting the pH value by using the pH regulator, fixing the volume, stirring and mixing uniformly, and filtering by using a sterilization filter to obtain the calcitriol injection. And filling into a brown ampoule, filling nitrogen, sealing, and sterilizing. The content of the calcitriol composition is obviously increased, the stability of the composition to light and air is improved, the reproducibility of a preparation process and the stability of a finished product are good, and the preparation method is suitable for batch production.