76 results about "Drug precursors" patented technology

The invention discloses a quinoline compound, and a preparation method, an intermediate, a medicinal composition and an application thereof / The invention provides a quinoline compound represented by formula 1 shown in the specification, and its pharmaceutically acceptable salts, solvates, metabolites, metabolism precursors or medicinal precursors. The quinoline compound has a good inhibition effect on tyrosine kinases C-Met, and can be used for preparing medicines for prevention, treatment or adjuvant treatment of many C-Met expression or activity related diseases, especially tumor diseases.

Disclosed are microcapsules comprising a polymer shell enclosing one or more immiscible liquid phases in which a drug or drug precursor are contained in a liquid phase. The microparticles also contain magnetic particles that can be heated by application of an external magnetic field and thus heated to a predetermined Curie temperature. Heating of the particles melts the polymer shell and releases the drug without causing heating of surrounding tissues.

The invention discloses a 7-ethyl-10-hydroxycamptothecine drug precursor, a preparation method and an application thereof. A structure formula of the drug precursor is represented as the formula I or II. The drug precursor is prepared through an esterification reaction between a C-10 hydroxyl group or a C-20 hydroxyl group of 7-ethyl-10-hydroxycamptothecine and a hydrophobic molecule. The drug precursor has excellent anti-tumor activity and can directly release active components in vivo in a hydrolysis manner without catalytic hydrolysis of carboxylesterase, thereby achieving a high bioavailability. The drug precursor not only has excellent solubility in water but also has great solubility in amphipathic surfactants, such as tween-80 and the like, wherein the solubility can reach more than 30 mg / ml, and a high stability is achieved even that the drug precursor is diluted in water. The drug precursor can be prepared just through a one-step esterification method, is high in yield and low in preparation cost, is high in stability and good in safety, satisfies requirements in clinical medication and in large-scale industrial production, and has excellent market prospect and clinical application value.

Nano-sized delivery systems consisting of an inorganic nano particle moiety covalently bonded to at least one organic pro-perfume or pro-drug moiety are disclosed. The systems of the invention are able to deliver perfuming or pharmaceutical active ingredients. Other aspects of the present invention include the use of such systems in perfumery as well as the perfuming compositions or perfumed articles that incorporate these delivery systems.

The invention discloses a precursor compound of a novel abiraterone drug, wherein the precursor compound provides improved oral bioavailability and drug dynamic characteristic. The drug is an irreversible inhibitor of human body CYP17 enzyme, can be used for treating urogenital system or androgen-associated cancers, diseases or sickness, for example, human prostate cancer, breast cancer and prostatic hyperplasia.

The present invention provides a pyrromonazole derivant shown in the formula (I). In the formula (I), R<1> is H, optional substituent C1-6 alkyl, etc.; one group in Q and T is a group represented by the formula (a) or a group represented by the formula (b), while another group is optional substituent C1-6 alkyl, etc.; X is a single bond, O or S; Y is a single bond, C1-6 alkylidene, etc.; R<3>, R<6> and R<7> are H, halogen atoms, etc.; the present invention also provides a pharmaceutically acceptable salt or a prodrug thereof. Showing excellent inhibitory activity for human SGLT1, the present invention can be used as drugs to prevent or treat hyperglycemia-related diseases (such as, diabetes, diabetic complications or obesity). The present invention also provides a drug compound of the derivants, a pharmic use thereof and an intermediate used for production.

This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V-(W)k-(X)1-A-Z, wherein: V is a specifier; (W)k-(X)1-A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)m wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclisation elimination spacer; Z is a therapeutic drug; k, 1 and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: - when A is (Y)m: k+1+m >= 1, and if k+1+m = 1; - when A is U: k+1 > / = 1.

A preparation method and application of anti-cancer volatile oil extracted from galangal ginger. After washing galangal root, slice it in a slicer, take galangal slices and put them in a flask, add distilled water and zeolite, mix well, soak and heat to Boil, keep slightly boiling, stop heating, let stand, read the volume of volatile oil, collect, extract, dry with an appropriate amount of anhydrous sodium sulfate, it will be a light yellow transparent oily liquid, and store it in a brown bottle. The galangal volatile oil of the invention significantly inhibits the growth of tumor cells; expands the scope of application of the galangal and increases the added value of the galangal; the preparation process is simple, the cost is low, simple and easy, and the practicability is strong. Searching for new anti-tumor drugs from natural active substances is an effective way to screen new anti-tumor drugs or drug precursors, and has a broad market.

The invention provides a method for screening anti-tumor metastasis compounds. By means of the change of the expression level of an EMT marker in tumor cells, a stable and effective system for screening the anti-tumor metastasis compounds is established, screening of a large quantity of compounds can be achieved, anti-metastasis new drug precursors can be found within a short period, and a technical solution is provided for developing a series of anti-cancer new drugs.

Belonging to the technical field of biochemical engineering, the invention discloses a preparation method of glycyrrhetinic acid monoglucuronide. The preparation method includes: taking licorice as the raw material, firstly preparing an extracted solution of glycyrrhetinic acid monoglucuronide, then performing clarification treatment, further conducting separation and purification, and finally drying the purified glycyrrhetinic acid monoglucuronide so as to obtain glycyrrhetinic acid monoglucuronide. The preparation method performs pretreatment on licorice through an external physical field, the process is scientific and reasonable, green and environmental protection, the operation is simple and practicable, and can realize continuous production. The glycyrrhetinic acid monoglucuronide prepared by the method has the characteristics of low cost, high production efficiency, high purity, easy popularization and high added value, can be used as a food additive and drug precursor, and provides raw material for the food and pharmaceutical industries.

The invention discloses a taxane prodrug, which has a structure of Y1-R-Y2, wherein the Y1 and the Y2 are docetaxel or cabazitaxel, R comprises a specific connecting bond for environmental response intumor cells, and the taxane prodrug is generated by carrying out substitution or condensation reaction on a taxane drug and a tumor microenvironment-responsive connecting bond. According to the invention, the prodrug has good anti-tumor activity, can directly release active ingredients in vivo in a hydrolysis or oxidation mode, and can avoid in vivo toxicity caused by direct injection of taxane drugs; the prodrug disclosed by the invention not only has good solubility in water, but also can be self-emulsified in water to form nanoparticles; and the prodrug can be obtained through a single-step reaction method, the yield is high, the preparation cost is low, the stability is high, the safety is good, the requirements of clinical medication are met, the requirements of large-scale industrial production are met, and the prodrug has good market prospects and clinical application value.

The present invention discloses a hydroxychloroquine amphiphilic polymer drug precursor. The hydroxychloroquine amphiphilic polymer drug precursor is composed of hydrophilic polyethylene glycol monomethyl ether and a hydrophobic hydroxychloroquine polymer. The hydroxychloroquine polymer is bonded to the polyethylene glycol monomethyl ether via a cleavable chemical bond. The hydroxychloroquine amphiphilic polymer drug precursor can be self-assembled into nanoparticles with a particle sizeof 20-300 nm in water, which improves pharmacokinetic behaviors of free hydroxychloroquine and enables the hydroxychloroquine amphiphilic polymer drug precursor to have significant long-cycle characteristics. At the same time, the hydroxychloroquine amphiphilic polymer drug precursor nanoparticles can loada variety of hydrophobic drugs, including camptothecin and derivatives thereof, paclitaxel, doxorubicin and bortezomib as well as various types of negatively charged drug molecules, and have a wide range of application values.

The invention discloses a disulfiram-based glucan nanometer prodrug, and a preparation method and applications thereof. The disulfiram-based glucan nanometer prodrug is a disulfiram-based glucan nanometer prodrug with oxidation-reduction response characteristics, glucan is selected as a skeleton, and a drug is connected with a polymer skeleton through a disulfide bond. The invention provides a polymer drug delivery system with oxidation-reduction response. According to the nanometer prodrug, the disulfide bond can be reduced into sulfydryl by reduced glutathione in cancer cells, and a responsemechanism is provided, so that the structure of a carrier is changed, and the drug is quickly released. The nanometer prodrug shows good biological safety and a good cancer cell killing effect, and an intelligent drug delivery system is provided for tumor treatment.

The present invention discloses a nitrogen-containing fused heterocyclic compound, as well as a preparation method, intermediate, composition and application thereof. The nitrogen-containing fused heterocyclic compound of the present invention as represented by formula (I), as well as the pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, metabolite or drug precursor thereof, exhibit a high selectivity and a high inhibitory activity with respect to CDK4 and CDK6 at a molecular level, an excellent inhibitory activity with respect to breast cancer cells at a cellular level, and significant inhibition of tumor cell proliferation associated with cyclin-dependent kinase activity at an animal level. The invention also exhibits a good stability with respect to human or mouse liver microsomes without significant inhibition of metabolic enzymes, good in vivo absorption in mice and rats, a high bioavailability and good druggability.

Methods are provided for the treatment of pulmonary hypertension and other conditions associated therewith. In particular, the methods include treatment of pulmonary hypertension with estradiol metabolite or estradiol metabolite associated with biodegradable microparticles or nanoparticles alone or in combination with another therapeutic agent. Preferred estradiol metabolites include 2-methoxyestradiol, 4-methoxyestradiol, 2-hydroxyestradiol, and 4-hydroxyestradiol, and / or to synthetic derivatives and analogues thereof or prodrugs thereof. The compositions may also be in the form of a controlled release formulation.

The present invention provides a hydroxyacyl-coenzyme A dehydrogenase gene, an acyl-coenzyme A thiolase gene, genetically engineered strains and a use thereof. The hydroxyacyl-coenzyme A dehydrogenase gene encodes a protein (i) or (ii) as follows: (i) having an amino acid sequence according to SEQ ID NO 2; (ii) derived by substituting, deleting or inserting one or more amino acids in the amino acid sequence defined by (i) and having the same function as that of the protein of (i). The present invention constructs genetically engineered Mycobacterium strains lacking of a hydroxyacyl-coenzyme A dehydrogenase gene or an acyl-coenzyme A thiolase gene, which are used in the preparation of steroidal compounds, such as 1,4-BNA, 4-BNA, 9-OH-BNA, etc . . . Further, the invention improves the production efficiency and product quality of steroidal drug, improves the utilization of drug precursors, reduces the production costs, and provides the advantages of mild reaction conditions, environmentally friendly, and high economic and social benefits.

The invention relates to clinical single-tube fluorine 18 multifunctional module equipment and a radiopharmaceutical synthesis process. The clinical single-tube fluorine 18 multifunctional module equipment comprises a fluorine-18 ioncapturing and releasingmodule, a high performance liquid chromatography column purification module and a product collection module, wherein the high performance liquidchromatography column purification module adopts liquid for intravenous injection as an HPLC mobile phase; a QMA column of the fluorine-18 ion capturing and releasing module captures fluorine-18 ionsgenerated from an accelerator, and the leacheate of the QMA column and a prodrug respectively enter a reaction tube for mixing with the HPLC mobile phase; the reaction tube is connected with an HPLCseparation column of the high performance liquid chromatography column purification module; the HPLC separation column is connected with the product collection module; and a product having been subjected to online dilution and sterile filtration membrane treatment can be used for intravenous injection. By adopting the equipment and the process provided by the invention, solvent conversion used bya common module can be avoided, a target compound can be correctly collected, the pH value and the radioactive concentration of the product can be adjusted on line, and the process is suitable for full-automatic preparation of clinically common positron emission drugs under a GMP condition.

The invention discloses a preparation method of a water-soluble paclitaxel anticancer drug, and belongs to the field of medicine. A PTX drug precursor has similar antitumor activity to a clinical drugPTX, can be hydrolyzed slowly in vivo, and effectively reduces the in-vivo toxicity. The PTX drug precursor has good solubility in water. The targeting property of the PTX drug precursor is increased. Hyaluronic acid is modified with anhydride and then is grafted to paclitaxel. The polymer has good injection safety, self-aggregation characteristics and drug loading capacity.

The invention discloses an exosome drug delivery system and its preparation method and application, and provides an active drug loading system that uses phospholipid compounds to load cisplatin prodrugs on exosomes, so as to solve the problem of membrane rupture caused by exosome drug loading strategy and low drug loading; the present invention prepares cisplatin prodrugs in advance, prepares them into liposomes, and then mixes them in exosomes to realize active drug loading, utilizing the fusion of phospholipid compounds and exosome membranes It protects the integrity of the exosome membrane and increases the drug loading capacity of the exosome anticancer drugs.

The invention discloses an acyl coenzyme A-reductase gene phsR and the application thereof. The acyl coenzyme A-reductase gene phsR has a nucleotide sequence shown as SEQ ID No. 1. The invention also provides an engineering strain with deletion of the acyl coenzyme A-reductase gene phsR. The engineering strain is named as Mycobacterium neoaurum Delta phsR, and has a collection number of CCTCC NO. M2016321. The engineering strain disclosed by the invention is capable of effectively eliminating 4-BNA by-products in the sterol degradation process, obviously improving the purity and the yield of AD, ADD, 9-OH-AD and other series of steroid products prepared by depending on the sterol degradation, reducing the cost of raw materials for producing steroid drugs and the energy consumption, improving the utilization rate of prodrugs and greatly simplifying the preparation process of AD and other steroid drugs, and has a high industrial application value.

The invention discloses a genetic engineering strain for producing a sterol side chain incomplete degradation product and a construction method and application thereof, and the construction method comprises the following steps: carrying out inactivation knockout on a gene in an igr operon in a microorganism capable of degrading and converting sterol, and carrying out deletion or / and overexpression on a key gene in a sterol metabolic pathway, therefore, a genetic engineering strain is obtained. The strains can be used for selectively preparing PDC, PDC-M, 1-PDC, 1-PDC-M, 9 alpha-OHPDC and 9 alpha-OHPDC-M, and further can be used for producing steroid drugs such as adrenocortical hormone and the like. According to the method, the production efficiency and the product quality of the steroid medicine can be greatly improved, the energy consumption in the steroid medicine production process is reduced, the production steps are simplified, the utilization rate of the medicine precursor is improved, so that the production cost is reduced, the overall reaction conditions are mild, the method is environment-friendly, and the economic value and the social value are relatively high.

The invention provides a diagnostic prodrug compound targeting fibroblast activating protein. The structure of the diagnostic prodrug compound is represented by a formula (I). The invention also provides a diagnostic medicine targeting a fibroblast activation protein, wherein the diagnostic medicine is a complex obtained by taking the compound represented by the formula (I) as a ligand and labeling the compound with 18FAl, and the structure of the diagnostic medicine is represented by the formula (II). The invention also provides a preparation method of the precursor compound and the diagnostic medicine, and an application of the precursor compound and the diagnostic medicine in preparation of nuclide imaging medicines for FAP protein high-expression tumors. According to the diagnostic nuclide medicine targeting the fibroblast activation protein, 18F nuclide which can be stably produced and has a long half-life period is adopted to replace 68Ga, the imaging effect of targeted FAP protein nuclide can be improved, and the nuclide medicine has the potential of being clinically popularized and applied.

The invention discloses a synthesis method of a three-function diagnosis and treatment integrated prodrug for prostate cancer and a product thereof. A compound 1 is used as a raw material, and the compound 1 and three different amino acids are used to gradually synthesize the three-function diagnosis and treatment integrated prodrug, so that the prodrug can obtain the ability to mark three radionuclides of 18F, 68Ga and 177Lu. The invention realizes that the marking rate of 18F reaches 40%, and the marking rate of 68Ga and 177Lu reaches 90% or more, and can be combined with other targeting molecules other than PSMA to design more bifunctional or trifunctional diagnostic drugs, the structure will greatly open the PSMA structure drug market, provide more, more flexible, more functional radionuclide marker options for such type of drugs, and have a great promotion effect on the diagnosis and treatment of prostate cancer, which is suitable for industrial popularization and use.

The invention belongs to the field of drug precursor preparations and discloses a preparation method of an oil-phase liquid crystal gel precursor preparation for a hydrophilic drug. The preparation method comprises following steps: a phospholipid dispersion and a hydrophilic drug solution are prepared firstly and mixed for preparation of an aqueous phase solution, then an oil phase solution is prepared, the oil phase solution and the aqueous phase solution are mixed and lyophilized, and a lyophilized sample is prepared; a mixed oil phase of phospholipid and glyceride is prepared, the mixed oilphase is added to the lyophilized sample and mixed uniformly, and the precursor preparation for the hydrophilic drug is prepared. The precursor preparation for the hydrophilic drug has good stability, can form gel in the presence of water, and has good slow-release effect. The system has the advantages of simple preparation process, small difference between batches, few influence factors and thelike, and new technology and new dosage form with great commercial transformation value are obtained.

The invention discloses a 7-ethyl-10-hydroxycamptothecine drug precursor, a preparation method and an application thereof. A structure formula of the drug precursor is represented as the formula I or II. The drug precursor is prepared through an esterification reaction between a C-10 hydroxyl group or a C-20 hydroxyl group of 7-ethyl-10-hydroxycamptothecine and a hydrophobic molecule. The drug precursor has excellent anti-tumor activity and can directly release active components in vivo in a hydrolysis manner without catalytic hydrolysis of carboxylesterase, thereby achieving a high bioavailability. The drug precursor not only has excellent solubility in water but also has great solubility in amphipathic surfactants, such as tween-80 and the like, wherein the solubility can reach more than 30 mg / ml, and a high stability is achieved even that the drug precursor is diluted in water. The drug precursor can be prepared just through a one-step esterification method, is high in yield and low in preparation cost, is high in stability and good in safety, satisfies requirements in clinical medication and in large-scale industrial production, and has excellent market prospect and clinical application value.

The invention discloses a nuclear medicine and magnetic resonance bimodal development drug precursor (DOTA-SPIONs-PEG-FA). The drug precursor takes superparamagnetic iron oxide nanoparticles as cores and is coated with a biocompatible material and a double functional chelating agent. Folic acid is connected to the superparamagnetic iron oxide nanoparticles through the biocompatible material. The bimodal development drug precursor is labeled by a radioactive metal nuclide, so that a brand-new nuclear medicine and magnetic resonance bimodal development drug (RM-DOTA-SPIONs-PEG-FA) is obtained for the first time. The drug is good in in-vitro stability, has very high initial uptake, a good tumor / blood ratio and a relatively long residence time in tumor if being applied to folate receptor positive tumor detection, moreover, the nanoparticles have obvious active targeting action on tumor, so that the drug precursor can be effectively suitable for MRI development and EPT or SPECT development.