53 results about "Thioketal" patented technology

Thioketals and thioethers are provided that inhibit the expression of VCAM-1, and which can be used in the treatment of VCAM-1 mediated diseases including inflammatory disorders, cardiovascular diseases, occular diseases, autoimmune diseases, neurological disorders, and cancer. The compounds also can be used to treat hyperlipidemia and / or hypercholesterolemia.

The invention discloses a Material for thioketal bonding doxorubicin and polyphosphate and a preparation method and application thereof. The method comprises the following steps: (1) using benzyl alcohol as an initiator, ring-opening polymerization of PPEG and phosphate ester monomer to obtain P (PPEG co AEP). (2) P (PPEG-Co-AEP (Cya)) was obtained by clicking on P (PPEG-Co-AEP) with mercaptoethylamine. (3) adding activated dipropionic acid containing thioketal bond into adriamycin for amide reaction. (4) P (PPEG-Co-AEP (Cya)) was synthesized by amidation reaction to give the material containing thioketal bonded doxorubicin and polyphosphate. The nanoparticles were self-assembled with photosensitizer, and the drug was rapidly released under 660 nm near-infrared light, the drug concentration and active oxygen content in tumor site increased, and the therapeutic effect of chemotherapy and PDT was improved. The nanoparticles have potential clinical application value.

The invention provides a preparation method of allylestrenol. The allylestrenol is prepared by a five-step reaction based on estr-4-ene-3,17-dione as a starting material. The method comprises the following steps: 1) carrying out dithioketal protection on 3-keto so as to obtain a compound (3); 2) carrying out dihydric alcohol ketal protection on 17-keto so as to obtain a compound (4); 3) removing 3-thioaketal through a Birch reduction reaction so as to obtain a compound (5); 4) hydrolyzing for 17-position deprotection so as to obtain a compound (6); and 5) carrying out Grignard reaction so as to obtain a target compound (1). Through a reaction route in the invention, the high-purity product is obtained in high yield and high selectivity; and operation is simple, synthesis route is short, and purification is convenient, thereby greatly reducing production cost. The method is suitable for industrial production.

The invention discloses a mercury ion fluorescence probe based on aggregation-induced emission and its preparation method and an application. An aggregation-induced emission molecule containing a ketone thioacetal structure unit is compounded by taking tetraphenyl ethylene as a raw material; the ketone thioacetal deprotection reaction promoted by mercury ion is organically combined with AIE performance, thus the prepared probe has the advantages which are excellent selectivity and sensitivity and strong solid emission performance. The probe synthetic method is simple, and the synthetic probe can be used as a ratio fluorescence sensor of the mercury ion solution; the detection reaction with the mercury ion can be completed within several seconds; thus the probe has high selectivity and sensitivity. Particularly, a test strip prepared by the compound has high sensitivity to the mercury ion; under the irradiation of the ultraviolet light, the detection limit of the mercury ion solution bythe test strip prepared by the compound is 1x10-5 mol / L through the visual observation. The preparation method of the test strip is simple in method, low in cost, convenient to use, and can be storedfor a long time.

The invention relates to a method for synthesizing glutaric acid from alpha-ketoglutaric acid. Specifically, under the mild condition, protected ketone thioacetal is subjected to catalytic hydrogenation reduction with raney nickel, recycling and reusing of reactants, solvent and a catalyst are achieved in a carbonyl reduction part in the most critical step, and the method for preparing the largely-demanded glutaric acid with the simple four-step method is developed. According to the method, the glutaric acid with the high yield is synthesized with the method for the first time, the yields of all steps are 92%, 78.6%, 90% and 85% in sequence, and the total yield is 55.32%; the method has broad prospects in synthetic application of compound library establishment.

The invention belongs to the technical field of high polymer materials, biomedical materials and photodynamic therapy, and relates to a preparation method and application of a polymeric porphyrin compound. The preparation method comprises the following steps: dissolving tetracarboxylic acid modified tetraphenylporphyrin in an organic solvent, wherein the concentration is 0.1-1M; adding a thioketalcomonomer with terminal diamino into a reaction system, and finally adding 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and 4-dimethylaminopyridine; heating the reaction system to 50-100 DEG C, and reacting for 24-72 hours; and after the reaction is finished, cooling to room temperature, settling and centrifuging, dialyzing an obtained crude product by using deionized water, and freeze-drying to obtain the polymeric porphyrin compound pPS.

The invention discloses a photodynamic therapy-chemotherapy combined prodrug capable of being activated by red light and preparation and application thereof. The preparation method comprises the following steps: chemically modifying 20-site hydroxyl of a chemotherapeutic drug camptothecin, introducing a connecting arm containing a thioketal structure, and covalently adding the connecting arm to a boron dipyrromethene photosensitizer through a click reaction to obtain a red light activatable photodynamic therapy-chemotherapy combined prodrug, namely the camptothecin-boron dipyrromethene conjugate. Meanwhile, the camptothecin-BODIPY conjugate is used as a research object, human liver cancer cells HepG2, human esophageal cancer cells EC109 and human cervical cancer cells HeLa are respectively used as tested cell strains, in-vitro anticancer activity research of the camptothecin-BODIPY conjugate is developed, and a foundation is laid for application of the camptothecin-BODIPY conjugate to combined treatment of cancers. The synthesis method of the compound is simple, raw materials are easy to obtain, the cost is low, side reactions are few, the yield is high, purification is easy, and industrial production is facilitated.

The presently-disclosed subject matter includes biodegradable scaffolds. Exemplary biodegradable scaffolds comprise a plurality of polythioketal polymers, and a plurality of polyisocyanates, where at least one polyisocyanate is linked to at least one polymer to form the scaffold. Thus, certain embodiments of scaffolds comprise a cross-linked network of the polythioketal polymers and the polyisocyanates. The presently-disclosed subject matter also includes methods for treating tissue, such as skin or bone tissue, in a subject in need thereof. Treatment methods comprise contacting the tissue with an effective amount of the biodegradable scaffold. Furthermore, the presently-disclosed subject matter includes methods for making the present biodegradable scaffolds.

The invention discloses a thioketal bond connected pegylated Ce6 material as well as a preparation method and application thereof. The method comprises the following steps: saturating a mixture of cysteamine hydrochloride and acetone with hydrogen chloride, and performing reaction to obtain diamine containing thioketal bonds; performing reaction on methoxy polyethylene glycol carboxyl, dicyclohexylcarbodiimide and N-hydroxysuccinimide, and dropwise adding a polyethylene glycol solution into a diamine solution containing thioketal for reaction to obtain mPEG-TK-NH2; dissolving chlorin e6, dicyclohexylcarbodiimide and N-hydroxysuccinimide in a solvent for reaction; and adding the activated Ce6 solution into the mPEG-TK-NH2 solution, and carrying out a stirring reaction to obtain the thioketal bond connected pegylated Ce6 material. The thioketal bond connected pegylated Ce6 material has biocompatibility and degradability, and can enhance the uptake of drug-loaded particles by cells, so that the drug concentration in the cells is improved, tumor cells are killed, and the chemotherapy effect is improved.

The invention discloses an oxidation response type nano-micelle, and a preparation method and application thereof. The oxidation response type nano-micelle is an amphiphilic active oxygen response type nano-drug delivery system, which is constructed by bonding a hydrophobic anti-tumour drug adriamycin and polyethylene glycol monomethyl ether through an oxidation response thioketal bond; an active oxygen response group in the nano-micelle is one of compounds sensitive to hydroxyl radicals, singlet oxygen or active oxygen; and the active oxygen sensitive compound is a thioketal group. The nano-micelle in the invention can generate a large amount of active oxygen and stimulate thioketal bond breakage under the sonodynamic effect, so that the nano-micelle releases the anti-tumour drug adriamycin; the adriamycin directly acts on tumour tissues; furthermore, damage to surrounding healthy tissues is greatly reduced; combined treatment of sonodynamic and chemotherapy is achieved; effective enrichment and time-space controlled release of the medicine at a tumour part are realized; and an effective anti-tumour effect is achieved.

The invention provides a method for reducing mercaptal or desulfurizing thioketal. According to the method, hydrazine hydrate serves as a reducer, and the mercaptal or thioketal is reduced into methylor methylene. The method provided by the invention is simple, convenient and environmentally friendly, can achieve safe conversion at a scale above a gram level, is applicable to the field of chemical industry medicines and can achieve large-scale production.

The invention relates to the technical field of biomedical materials, in particular to a preparation method and application of an ROS response marine fucoidin nano-carrier based on a Fenton reaction and an AIE effect. The ROS response marine fucoidin nano-carrier based on the Fenton reaction and the AIE effect is constructed, the fucoidin nano-carrier is composed of at least two amphiphilic block copolymers, the amphiphilic block copolymers take fucoidin as a main chain, the side chain contains at least one of thioketal or a photosensitizer, the side chain of at least one amphiphilic block copolymer is grafted with a Fenton reaction catalyst, the thioketal has an ROS response characteristic, the photosensitizer has a photodynamic function, and the Fenton reaction catalyst can further promote the ROS corresponding mechanism through a Fenton reaction, so that the fucoidan nano-carrier can make anti-tumor drugs realize the function of combined treatment of tumor by chemical kinetics, photodynamics and chemotherapeutic drugs at the same time, and play the function of the anti-tumor drugs.

The invention discloses an amphiphilic nanocage with active oxygen sensitivity, a preparation method and application thereof. The amphiphilic nanocage is prepared by the steps of: firstly, forming a nanoemulsion from amphiphilic polybetaine and a thioketal bond-containing small molecular compound with active oxygen sensitivity, and then carrying out reaction under the action of an initiator. The amphiphilic nanocage has amphipathy, high stability, also has active oxygen sensitivity, and can be disintegrated under the action of active oxygen. When the nanocage is a carrier complex protein, theprotein can be included in the nanocage, the protein stability is improved, and transportation of the protein is utilized; after the protein-loaded nanoparticles enter the body, under the action of active oxygen, the external nanocage is disintegrated, and internal protein is released, thus playing a role at a focus part.

The present invention relates to a bicyclic thioketal cysteine-N-ring carboxylic anhydride and its preparation method and application, bicyclic thioketal cysteine-N-ring carboxylic anhydride, its structural formula is as follows: the bicyclic thioketal cysteine-N-ring carboxylic anhydride containing thioketal group designed and synthesized by the present invention contains two N-carboxyl ring anhydride units and a thioketal connecting unit, the N-carboxyl ring anhydride unit can self-polymerize, and can also be copolymerized with other amino acid ring anhydride monomers, using amino-terminated polyethylene glycol monomethyl ether as an initiator for the polymerization reaction, an amphiphilic block copolymer can be obtained, which can be self-assembled into a nanostructure and efficiently coated with hydrophobic drugs. Because the thioketal structure is sensitive to ROS, once the drug carrier reaches the lesion site, the thioketal structure is immediately oxidized and broken, causing the disintegration of the carrier and the release of drug molecules, thereby exerting its functional effect.

The present invention discloses a near-infrared photosensitizer-based nanotherapeutic agent, its preparation method, and application. The near-infrared photosensitizer-based nanotherapeutic agent comprises a protein and a near-infrared prodrug bound to a hydrophobic cavity of the protein. The near-infrared prodrug comprises a near-infrared photosensitizer connected to a cupric sulfide bond and a chemotherapy drug bound to the near-infrared photosensitizer connected to the cupric sulfide bond via a thioketone bond. The near-infrared photosensitizer-based nanotherapeutic agent provided by the present invention significantly improves the solubility and bioavailability of the chemotherapy drug and the near-infrared photosensitizer, achieves tumor targeting and selectivity, thereby increasing the drug accumulation at the tumor site, improving the therapeutic effect, and reducing toxic side effects. This solves the problems of existing near-infrared fluorescent dyes, which have limited targeting and selectivity and low therapeutic effect.

The application belongs to the technical field of organic synthesis, and discloses a deprotection method of thioacetal or thioketals, which comprises the following steps: taking thioacetal or thioketals shown in formula-I as a reaction substrate, taking triiodine reagent shown in formula-II as an oxidant, adding into a mixed solvent of water and an organic solvent, and adding an acid as an activator to carry out a mixing reaction, so as to obtain aldehyde or ketone compounds shown in formula-III, and complete the removal of thioacetal or thioketals protective groups; wherein X in the thioacetal or thioketals is selected from S, O or N; R 1 , R 2 , R 3 are each independently selected from hydrogen, methyl, methoxy or halogen. Through the method of the application, the efficient removal of thioacetal or thioketals protective groups under mild conditions is realized by taking triiodine reagent as an oxidant. The reaction route of the method is as follows:

The invention relates to preparation and application of ROS (reactive oxygen species) responsive nanoparticles containing thioketal bonds, which can effectively solve the problems of poor biocompatibility, poor water solubility, uncontrollable release and the like of curcumin. The materials comprise curcumin, 4-carboxyphenylboronic acid, chitosan oligosaccharide and thioketal diacid. Chitosan oligosaccharide is modified by 4-carboxyphenylboronic acid, and then thioketal diacid is cross-linked to obtain the ROS responsive polymer. The polymer, curcumin and glucose oxidase are self-assembled in a solution to construct ROS-responsive nanoparticles. According to the nanoparticles prepared by the invention, due to the introduction of ROS-sensitive thioketal bonds and boric acid ester bonds, the controlled release of curcumin at a tumor part is realized under the stimulation of a tumor microenvironment. In addition, the encapsulated glucose oxidase can catalyze over-expressed glucose at tumor tissues to generate hydrogen peroxide, the ROS concentration of tumor cells is increased, the drug release efficiency is enhanced, and the treatment effect of the drug on breast cancer is effectively improved.

The invention provides a desulfurization method for reducing thioacetal or thioketal. In the method, hydrazine hydrate is used as a reducing agent to reduce thioacetal or thioketal to methyl or methylene. The process of the invention is simple and environment-friendly, and can be safely transformed on a scale above the gram level, is applicable to the field of chemical medicine and medicine, and can realize large-scale production.

The invention belongs to the technical field of organic synthesis, and discloses a deprotection method of thioacetal or thioketal, which comprises the following steps: adding thioacetal or thioketal as shown in a formula-I as a reaction substrate and a trivalent iodine reagent as shown in a formula-II as an oxidizing agent into a mixed solvent of water and an organic solvent, adding an acid as an activating agent, and reacting to obtain the thioacetal or thioketal. Carrying out a mixed reaction to obtain an aldehyde or ketone compound as shown in a formula-III, and completing removal of the thioacetal or thioketal protecting group; wherein X in the thioacetal or the thioketal is selected from S, O or N; r1, R2 and R3 in the trivalent iodine reagent are independently selected from a hydrogen group, a methyl group, a methoxyl group or halogen. According to the method disclosed by the invention, the trivalent iodine reagent is used as the oxidizing agent, and efficient removal of the thioacetal or thioketal protecting group under a mild condition is realized. Specific reaction route of the method is as follows: # imgabs0 #

The invention belongs to the technical field of high polymer materials, biomedical materials and photodynamic therapy, and relates to a preparation method and application of a polymeric porphyrin compound. The preparation method comprises the following steps: dissolving tetracarboxylic acid modified tetraphenylporphyrin in an organic solvent, wherein the concentration is 0.1-1M; adding a thioketalcomonomer with terminal diamino into a reaction system, and finally adding 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and 4-dimethylaminopyridine; heating the reaction system to 50-100 DEG C, and reacting for 24-72 hours; and after the reaction is finished, cooling to room temperature, settling and centrifuging, dialyzing an obtained crude product by using deionized water, and freeze-drying to obtain the polymeric porphyrin compound pPS.

The invention discloses a degradable thioketal (aldehyde) epoxy resin curing agent as well as a preparation method and application thereof, which can solve the problems of harsh degradation conditions, unadjustable degradation rate, poor thermal performance and the like of the existing epoxy resin material. The curing agent provided by the invention is simple in preparation method and low in toxicity, and can be prepared at a hectogram level or above; curing agents with different chemical structures can be obtained by replacing different reactants; the curing agent has various functional groups and can be further modified according to requirements; the degradation rate of the cured epoxy resin is adjustable, and the initial temperature of the curing reaction is diversified. Because thioketal has stable chemical properties, the cured epoxy resin has better thermal stability, thermal mechanical properties and acid-base stability than common degradable epoxy resin (Schiff base, ketal and the like), is equivalent to or even surpasses non-degradable epoxy resin, can be degraded in the presence of an oxidizing agent or metal ions, has unique degradation conditions, and is suitable for industrial production. A new thought is provided for epoxy resin degradation.

The invention discloses a preparation method and application of lipid gel for drug sustained release, and belongs to the field of biomedical materials. The lipid gel is obtained by physically mixing a liposome solution and a hydrogel material, the particle size of the liposome is 100-200 nm, the liposome can be kept stable within 14 days, the aperture of the hydrogel is 200-800 nm, and the hydrogel is of a three-dimensional network structure. The preparation method comprises the following steps: firstly, carrying out reactions such as amidation, deprotection reaction and thioketonization reaction to obtain lipoid molecules, forming lipidosome through self-assembly of the lipoid molecules, and then compounding the lipidosome with hydrogel formed by photo-crosslinking to prepare the lipid gel composite material with drug sustained release capability. The preparation process is simple, the conditions are mild, the drug structure is not damaged, the prepared liposome has time stability and active oxygen response capability, the used chemical reagents are few, and the selectable range is wide.

The invention discloses a material in which adriamycin and polyphosphate are bonded by a thioketal bond, a preparation method and an application thereof. The method comprises the following steps: (1) using benzyl alcohol as an initiator, ring-opening polymerization of PPEG and phosphate monomers to obtain P(PPEG-co-AEP). (2) Click mercaptoethylamine onto P(PPEG‑co‑AEP) to get P(PPEG‑co‑AEP(Cya)). (3) Add the activated dipropionic acid containing thioketal bond to doxorubicin for amide reaction. (4) P(PPEG‑co‑AEP(Cya)) was subjected to amidation reaction to obtain a material containing thioketal bonded doxorubicin and polyphosphate. The material self-assembles with the photosensitizer into nanoparticles, and under the irradiation of 660nm near-infrared light, the drug is released rapidly, the drug concentration and active oxygen content in the tumor site are increased, and the effect of chemotherapy and PDT treatment is improved, which has potential clinical application value.

The invention relates to a spiro ammonium salt, a one-dimensional / two-dimensional perovskite crystal and a preparation method and application of the one-dimensional / two-dimensional perovskite crystal. Based on 3-mercaptopropylamine hydrochloride or 2-mercaptoethylamine hydrochloride, cyclohexanone or a derivative thereof is directionally converted into two spiro ammonium salts by adopting a thioketal reaction; then, based on the two spiro ammonium salts as ligand molecules, one-dimensional perovskite with a nanowire structure and a two-dimensional perovskite crystal material with a layered structure are directionally prepared, and the purpose of directionally regulating and controlling the dimension (one-dimensional or two-dimensional) of the perovskite through the ligand structure (the number of heterocycle atoms) is achieved; in addition, the one-dimensional / two-dimensional perovskite crystal material disclosed by the invention is excellent in crystal quality, obvious in characteristic absorption signal and high in PL emission intensity; the ligand molecule provided by the invention has strong qualitative expandability for one-dimensional and two-dimensional perovskite, and is beneficial to deep excavation of an influence mechanism of exciton emission in low-dimensional perovskite and design and preparation of more one-dimensional and two-dimensional perovskite with characteristic free exciton luminescence characteristics.

The invention relates to the technical field of high polymer materials, in particular to a self-repairing metal supramolecular elastomer based on thioacetal / thioketal coordination group coordination crosslinking and a preparation method thereof, and the self-repairing metal supramolecular elastomer based on the thioacetal / thioketal coordination group can be directly synthesized through a one-step method. Or a fractional step method can be adopted, namely, a linear polymer with the main chain being thioacetal / thioketal or containing a thioacetal / thioketal group is synthesized at first, then a thioacetal / thioketal coordination group is introduced for coordination cross-linking, and finally the self-repairing metal supramolecular elastomer is obtained. The obtained elastomers are transparent and extremely tough, the mechanical properties and thermal properties of the elastomers can be adjusted within a certain range by adjusting the composition of the copolymers and the density of coordinate bonds, and the method is suitable for ion coordination of thioacetal / thioketal groups, and can be used for ion coordination of the thioacetal / thioketal groups. And linear polymers of which the main chain is thioacetal / thioketal and contains thioacetal / thioketal groups are covered.

The invention relates to the technical field of medicines, in particular to gambogic acid-manganese nanoparticles and application thereof. The gambogic acid-manganese nanoparticles are mainly obtained by combining a complex of gambogic acid and divalent manganese ions with an oxidation-sensitive high-molecular polymer; a monomer for preparing the oxidation-sensitive high-molecular polymer comprises an ROS responsive structural unit with a thioketal group; monomers for preparing the oxidation-sensitive high-molecular polymer further comprise 1, 2, 4, 5-cyclohexane tetracarboxylic dianhydride and a water-soluble group.

The invention discloses an active oxygen (ROS) response type targeted liposome double-drug co-delivery system for treating pulmonary fibrosis as well as a preparation method and application thereof, and belongs to the technical field of biological medicine and nano-drug delivery. Structural phospholipid, charged phospholipid, cholesterol and a polyethylene glycol-phospholipid derivative containing a thioketal bond and cRGD peptide are used as membrane materials, GC-1 is embedded into a phospholipid bilayer through a membrane hydration-extrusion method, salvianolic acid B is encapsulated in the liposome, and the liposome with negative electricity on the surface is prepared. Negative charges on the surface of the liposome are beneficial to penetrating an airway mucus barrier and reducing alveolar macrophage removal, the modified cRGD enables the liposome to be enriched in a fibrosis focus, and the thioketal bond fractured liposome rapidly disintegrates and releases drugs in a high ROS environment in a focus area. The synergistic treatment that GC-1 promotes alveolar epithelium type II cells to be redifferentiated into type I cells and salvianolic acid B removes ROS is achieved, and therefore the pulmonary fibrosis process is efficiently reversed.

The invention discloses a red light-activatable photodynamic therapy-chemotherapy combined prodrug and its preparation and application. The present invention chemically modifies the 20-position hydroxyl group of the chemotherapeutic drug camptothecin, introduces a connecting arm containing a thioketal structure, and then covalently attaches it to the fluorobodipyrrole photosensitizer through a click reaction to obtain a red light-activatable Photodynamic therapy-chemotherapy combined prodrug: camptothecin-fluoroboron dipyrrole conjugate. At the same time, the present invention takes camptothecin-fluoroboron dipyrrole conjugate as the research object, and uses human liver cancer cell HepG2, human esophageal cancer cell EC109 and human cervical cancer cell HeLa as the test cell lines respectively to develop its anticancer activity in vitro The study laid the foundation for the application of camptothecin-fluoroborate dipyrrole conjugates in combination therapy for cancer. Moreover, the synthesis method of this type of compound is relatively simple, the raw materials are easily obtained, the cost is low, the side reactions are few, the yield is high, and the purification is easy, which is beneficial to industrial production.

The invention provides a preparation method and application of a polyfluoroalkyl thioketal derivative, and belongs to the technical field of organic chemical synthesis. The polyfluoroalkyl thioketal derivative disclosed by the invention has a structure as shown in a formula I which is described in the specification. According to the invention, a phosphoric acid buffer salt solution and acetonitrile are used as reaction solutions, and a polyfluoroalkyl thioketal derivative molecular skeleton is constructed through continuous nucleophilic substitution and Michael addition reaction processes. The polyfluoroalkyl thioketal derivative synthesized by the preparation method disclosed by the invention has an inhibition effect on MDA-MB-231 human breast cancer cells. The method is low in cost, simple and convenient to operate, economical and green, and has a good industrial application prospect.