3017 results about "Anti-Tumor Drugs" patented technology

The present invention relates to a pentacyclic triterpanoid derivative of multiple-oxide substitution of the A ring and the C ring and the medicine salt or solvate of the derivative, and the present invention also relates to the preparation method, the drug combination, and medical use of the derivative. The compound of the present invention has the functions of inhibiting the activity of six human tumor cell strains in vitro, such as human prostate cancer cell (PC-3), nasopharyngeal carcinoma cells (CNE), oral squamous carcinoma cell(KB), human lung cancer cell (A549), human hepatoma cell (BEL-7404), and human cervix cancer cell (Hela), and the function of the invention is at the same magnitude of the positive control of cisplatin, thereby the compound can be used as expected antitumor drug. The compound of the present invention also inhibits the alpha glucosidase strongly, and the inhibiting effect is greater than the positive control of acarbose, thereby the compound can be used as expected medicine for preventing and treating diabetes and the treatment of the virus diseases.

The invention relates to the field of pharmaceutical chemistry and specifically discloses an aryl ruthenium-beta-carboline complex and its preparation method and application. The aryl ruthenium-beta-carboline complex is [Ru(Eta6-arene)(N-N)Cl](PF6), wherein Eta6-arene is aryl ligand p-cymene(p-cymene, CYM) or benzene(benzene, Ben), N-N is beta-carboline alkaloid derivative1-(2-pyridine)-9H-pyridine[3,4-b]indole(L1), 1-(2-quinoline)-9H-pyridine[3,4-b]indole(L2) or 1-(2-imidazole)-9H-pyridine[3,4-b]indole(L3). The complex provided by the invention has very outstanding activity in in-vitro antitumor screening. In addition, in comparison with cancer cell lines, toxicity of the complex to normal cells is greatly reduced, and the complex has a good potential for development of antitumor drugs.

The invention discloses 20 kinds of 5-(bi(3-(2-ethoxy)-1H-indol-2)methyl)-2-hydroxy benzoyl-AA-OBzl, discloses a preparation method of the 5-(bi(3-(2-ethoxy)-1H-indol-2)methyl)-2-hydroxy benzoyl-AA-OBzl, discloses an effect of the 5-(bi(3-(2-ethoxy)-1H-indol-2)methyl)-2-hydroxy benzoyl-AA-OBzl in inhibiting invasion and metastasis of a tumor cell, discloses an activity of the 5-(bi(3-(2-ethoxy)-1H-indol-2)methyl)-2-hydroxy benzoyl-AA-OBzl in inhibiting weight gain of a tumor body of a S180-bearing mouse, and discloses an anti-tumor pulmonary metastasis activity and an anti-inflammatory activity. The compound has an excellent application prospect in preparing an antitumor drug, an anti-tumor metastasis drug and an anti-inflammatory drug.

The invention relates to preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof with anti-tumor activity and biodegradability. The conjugate has amphiphilicity by using alkylenediamine as a connecting arm and introducing hydrophobic segmer, namely a carboxyl-containing anti-tumor medicament, on a polysaccharide framework, and are formed into nanometer micelles by self-assembly in water. The invention is characterized in that 1) the anti-tumor medicament is physically coated by a hydrophobic inner core consisting of hydrophobic groups so as to remarkably improve the solubility of the anti-tumor medicament; and 2) the anti-tumor medicament obtained by chemical conjugation and physical coating can jointly achieve treatment effect and improve medicament action. The polysaccharide conjugate and the medicinal compositions thereof can be used for injection, oral administration, external use or mucosa administration. The invention has the advantages of simple preparation method, mature technology, high yield, and suitability for large-scale continuous production.

The invention belongs to the field of medicine, and in particular relates to a medical application of 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl 4-((3-chloro-4-methylphenyl) amino)-4-oxobutanoate in a selective histone lysine-specific demethylase 1 (LSD1) inhibitor, especially the application in anti-tumor medicaments. Pharmacodynamic tests indicate that the 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl 4-((3-chloro-4-methylphenyl) amino)-4-oxobutanoate has a remarkable LSD1 inhibiting effect, and has selectivity to homologous proteins MAO-A (monoamine oxidase-A) and MAO-B.

The invention relates an amphiphilic polysaccharide-anti-tumor medicament conjugate capable of releasing medicines specifically at a lesion site of a living body, as well as a preparation method and application of a medicinal composition of the amphiphilic polysaccharide-anti-tumor medicament conjugate. In the conjugates, hydrophobic anti-tumor medicaments are introduced into a polysaccharide skeleton through a connecting arm which contains a disulfide bond, so that the polysaccharide-anti-tumor medicament conjugate has amphipathic characteristics and can be self-assembled into nano-micelles; the nano-micelles can load anti-tumor medicaments additionally and also can be directly used as conjugate pre-drug micelles. The amphiphilic polysaccharide-anti-tumor medicament conjugate is mainly characterized in that 1) after the nano-micelles reach the lesion site, the disulfide bond connecting arm of the conjugate can be specifically degraded by high-concentration reducing substances in lesion cells, so that the micelles are depolymerized and the medicament is released quickly, and therefore, the treatment effect is improved; 2) the anti-tumor medicament is chemically conjugated and physically coated to achieve a common treatment effect. The polysaccharide conjugate and the medicinal composition thereof can be used for injection, oral administration or external use administration; the anti-tumor activity can be improved remarkably; new ideas are provided for the development of anti-tumor medicaments.

The invention relates to modification of a cell penetrating peptide for realizing a low-toxicity administration system with a positive targeting selecting function. A shielding peptide, an enzymolysis substrate peptide and a cell-penetrating peptide are connected in sequence, so that an activatable cell penetrating peptide is formed; and a medicament and/or a tracer and/or a medicament carrier is connected or embedded or adsorbed to the cell penetrating peptide, so that an administration system is constructed. According to a shielding peptide sequence, positive charges carried on the surface of the administration system can be reduced or completely neutralized, the cell penetrating capability of the cell penetrating peptide is shielded, and the toxicity of the administration system on normal cells of an organism is lowered; and an enzymolysis substrate peptide sequence can be identified by enzyme systems secreted specifically by different pathological change tissue cells and fractured by enzyme hydrolysis, so that a cell penetrating peptide is released and is used for carrying a medicament and/or a medicament carrier through a cell membrane, and the medicament enters cells and is brought into play. The invention aims to actively convey an antitumor medicament to tumor tissues in a targeted way and make the antitumor medicament enter tumor cells to a larger extent by using the administration system which can be used for activating a cell penetrating function, so that the toxicity at a non-tumor position is lowered while the antitumor effect of the medicament is enhanced.

The invention discloses a 3-epi-bufalin 3-O-beta-D-glucoside and derivant, which inhibits cancer cell from growing rather than bufalin to make cardiotonic, local anesthesia, combat shock and tumour-resistant drug.

The invention relates to pentadeuteropyridine compounds represented by the following formula (I) and pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof, and a preparation method, pharmaceutical compositions and uses thereof. The compounds can generate an inhibitory effect on variation forms of epidermal growth factor receptor (EGFR) protein kinase, thereby effectively inhibiting the growth of a variety of tumor cells; the compounds can be used for preparation of antitumor drugs, are used for treatment or prevention of a plenty of different cancers, and moreover, can overcome the drug resistance induced by conventional drugs gefitinib, erlotinib and other first-generation EGFR inhibitors. More specifically, the compounds can be used for preparation of drugs for treatment or prevention of diseases, obstacles, disorders or illness conditions mediated by certain variation-form epidermal growth factor receptors (such as L858R activated mutants, Exon19 deletion activated mutants, and T790M resistance mutants).

The invention relates to a common carrier material based on graphene oxide for a targeting anticancer drug and a gene and application and application. Folic acid, lactobionic acid and other tumor cell targeting or liver targeting molecules and part of amino groups of soluble chitosan are connected by amide bonds to prepare a conjugate, the conjugate is then connected with graphene oxide, quaternization is performed by using an epoxy compound with a quaternary ammonium group, and gene molecules are loaded by the quaternizationquaternized part of the chitosan through electrostatic attraction; and then the anticancer drug is loaded by pi-pi conjugates, hydrogen bonds and hydrophobic effects in a non-covalent bond method. By adopting the targeting performance of targeting molecules and effects of graphene oxide of a particular size to enhance penetration and retention in tumor tissues and combining the performance of the graphene oxide for pH response control release of the loaded drug, the drug can be realized released in a tumor cell, an intelligent delivery system for the common carrier of the tumor targeting or liver targeting anticancer drug and the gene is synthesized from the perspective of synergetic medication, and a theoretical basis and a method basis are provided for combined therapy of tumor.

The invention provides a preparation method of a mono-dispersed gelatin embolic microsphere with a precisely-controlled particle size. In the provided method, micro water-in-oil liquid drops are formed in a micro channel reactor at first through a micro-fluidic liquid drop control technology, then a crosslinking agent and a gelatin water solution are taken as the dispersing phase and introduced into the water-in-oil system, and then the mixture is directly cured to form microspheres. By adjusting the flowing speeds of the continuous phase and the dispersing phase, and the flowing speeds of two dispersing phases, the particle size and sphericility can be precisely controlled. The preparation technology is simple and rapid, and the process is controllable. The prepared gelatin microsphere can be used as an embolic agent or an antitumor drug carrier, and can also be applied to cell culture.

An application of the pentacyclo-triterpenoid used as the glycogen phosphorylase for preparing the medicines to treat diabetes, ischemic cardiovascular and cerebrovascular diseases, and tumor is disclosed.

An orally-disintegrating tablet of fluterazole for treating tumor contains tegafur, Jimosite and potassium oxyazinate. It has agreeable taste.

The invention belongs to the field of biomedicines, and relates to applications of chrysophanol or a derivative thereof and oncolytic virus in preparation of antitumor drugs. The invention finds that chrysophanol or the derivative thereof can be used for preparing oncolytic virus antitumor synergistic agents for the first time. Meanwhile, the invention also relates to a pharmaceutical composition containing chrysophanol and oncolytic virus, a medicine suit containing chrysophanol and oncolytic virus, and applications of chrysophanol and oncolytic virus in treatment of tumors, particularly tumors insensitive to the oncolytic virus.

The invention relates to a somatostatin receptor-mediated tumor targeted pharmaceutical composition which adopts a targeted somatostatin receptor functional polypeptide and polyethylene glycol for simultaneously modifying a pharmaceutical carrier, and an anti-tumor drug or/and an anti-angiogenic drug is delivered to the tumor part, thereby enhancing the tumor treatment effect.

The invention relates to a novel bufadienolides compound and a preparation method and application thereof, and provides a bufadienolides compound having a general formula (I) or pharmaceutical acceptable salts as well as bufadienolides extract or medication composition containing the compound. The compound and the extract have effect for inhibiting tumour cell activity and application to preparation of anti-tumour drugs. The invention also provides the preparation method applicable for industrial production of the compound and the extract.

The invention provides a rare earth upconversion nano crystal/silver difunctional composite nano material and a preparation method thereof as well as application thereof in preparation of medicine for treating tumour. The composite nano material can inhibit the growth of tumour tissue and can be used with anti-tumour medicine, thus improving medicine effect and achieving the aim of treatment; thecomposite nano material is difficult to decompose and has good light stability; damage to human body is less, the composite nano material can be taken as heat sensitizing agent and can absorb infrared light, the near infrared region (800-1200nm) is a transmission window of organism tissue, and damage of near infrared laser to human body is far less than that of laser in other wavebands, thus reducing damage to human body, being capable of being used as photothermal conversion agent and being superior when used for diagnosis and treatment on malignant tumour.

The invention discloses a deuterated palbociclib derivative, and a preparation method and an application thereof. A structural formula of the deuterated palbociclib derivative is as shown in a formula (I), a formula (II), a formula (III) or a formula (IV). According to the deuterated palbociclib derivative disclosed by the invention, through selective deuteration of palbociclib, the pharmacokinetic property of the medicine is improved, thus the curative effect, the safety and the tolerance of the medicine are improved. According to the deuterated palbociclib salt disclosed by the invention, the solubility and the dissolution rate of the medicine are improved; a new compound is provided for synthesis of a novel anti-tumor medicine through synthesis of the deuterated palbociclib derivative; and the deuterated palbociclib derivative has similar biologic activity to the palbociclib, and has a good medicine application prospect.

The invention relates to the technical field of biological medicines, and particularly to an amphiphilic conjugate nano-particle for treating tumors, as well as a preparation method and application of the amphiphilic conjugate nano-particle. The nano-particle comprises an amphiphilic conjugate formed by esterification of a carboxyl containing hydrophobic anti-tumor medicine and a hydroxyl hydrophilic anti-tumor medicine. Compared with the prior art, self-assembly of the amphiphilic conjugate in water can be achieved to form the nano-particle, no medicine is required for conveying a carrier, the conjugate can achieve the medicine conveying, and the nano-particle can enter a tumor cell more effectively and reduce the toxic and side effects for normal cell through permeability enhancing and retention effects of a tumor tissue; and after the conjugate nano-particle enters the tumor cell, two types of antitumor medicines can be released through ester bond degradation, and the purpose of collaborative treatment of cancers by the two types of medicines can be achieved.

The invention discloses a water-soluble targeting protein-polyethylene glycol-anticancer medicament junctional complex with targeting function and a preparation method thereof. The targeting protein-polyethylene glycol-anticancer medicament junctional complex provided by the invention is characterized by ensuring that the dissolvability of an anticancer medicament is improved, the in-vivo half-life period of the medicament is prolonged, and the anticancer medicament is selectively targeted so as to be released to tumor cells by virtue of the tumor passive targeting function of the macromolecular junctional complex and the tumor active targeting function of targeting protein specifically combined with the tumor cells. The preparation method of the junctional complex is characterized in that polyethylene glycol is utilized as a raw material to synthesize a heterobifunctional polyethylene glycol derivative, wherein one end of the heterobifunctional polyethylene glycol derivative is carboxyl, and the other end of the heterobifunctional polyethylene glycol derivative is maleimido; and the carboxyl end of the derivative is in covalent connection with the anticancer medicament, the maleimido end of the derivative is in covalent connection with the targeting protein, thus the targeting protein-polyethylene glycol-anticancer medicament junctional complex is obtained.

A comprehensive localized therapy method and equipment for tumor features that various endoscopes are used to inject the magnetic immune microspheres carrying biologic medicine and the antineoplastic magnetic chemical medicine into tumor focus, the liquid radioactive source is poured in the inner cavity of catheter, and an alternative magnetic field is generated around the tumor focus to induce the microspheres to generate heat and adsorbing the antineoplastic medicine to round the tumor focus. Its advantage is the combination of biotherapy, chemicotherapy, radiotherapy and thermotherapy.

The invention discloses a type of amino acid modified curcumin, a synthesis method thereof, and an application thereof. According to the invention, structural modification is carried out upon curcumin by using natural amino acid, such that 1-(4-hydroxy-3-methoxyphenyl)-7-(4-oxyacetyl amino carbobenzoxy-3-methoxyphenyl)-1,6-heptadiene-3,5-diketone which is represented by a general formula (I) is obtained. With an MTT method, evaluation is carried out upon the compound represented by the general formula (I) in the inhabitance of proliferation activities of four cells which are K562, H22, HL60 and S180. IC50 values of the compound represented by the general formula (I) in inhibiting the proliferations of the four tumor cells are calculated. As a result of experiments, with the compound represented by the general formula (I), proliferations of tumor cells can be substantially inhibited. The compound has excellent anti-tumor activity, and can be prepared into anti-tumor medicines.

The present invention relates to a conjugate of hydrophilic polymer-multicarboxyl oligopeptide and drug molecule of the following formula:

wherein: P is a water soluble polymer; m is an integer of 2˜12; j is an integer of 1˜6; R_i is a group selected from H, C_1-12 alkyl, substituted aryl, aralkyl, heteroalkyl and substituted alkyl; X and Z are linking groups; and TA is drug molecule. The conjugate has low toxicity and an ability to carry more than one drug molecule to improve solubility, sustain and control drug release, and has a remarkably enhancing effect especially to antitumor drug such as paclitaxel and camptothecin etc.

This invention discloses a new camptothecin derivate of 20-position esterification, its preparation, containing their medicine combination, and its usage of using it as medicine, especially as antitumor drug.

The invention relates to a hyaluronic acid-modified amphipathic chitosan derivative carrier with tumor microenvironment specificity drug release effect. The hyaluronic acid-modified amphipathic chitosan derivative carrier is characterized in that firstly, a hydrophilic group is introduced into a chitosan skeleton; then, a hydrophobic group is introduced into a specifically degradable link arm containing disulfide bonds, so as to realize the amphipathic function; the amphipathic derivative is assembled into nanomicelle by self in a waterborne medium, and is further modified by a charge adsorbing principle to target the molecular hyaluronic acid; the nanomicelle can effectively load an anti-tumor drug, and the hyaluronic acid is targeted to the tumor microstructure and then is degraded by hyaluronic acid enzyme in focus cells, so that the drug can be quickly released from the nanomicelle to act on the focal part, thereby obviously improving the concentration, therapy effect and biological utilization degree of free drug on the focal part. The hyaluronic acid-modified amphipathic chitosan derivative carrier has the advantages that the carrier which carries pharmaceutical activity or pharmacological activity molecules can be applied to internal injection of blood vessels or muscles or oral administration, so as to obviously improve the anti-tumor activity of drug; the preparation method is simple, the technology is matured, and the preparation method is suitable for large-scale production.

The invention discloses substituted-evodiamine anti-tumor and antifungal compounds and a preparation method thereof. The compounds have a general structural formula (I), wherein R represents: (1) benzyl or substituted benzyl; (2) benzoyl or substituted benzoyl; (3) linear or branched alkyl having 2 to 6 carbon atoms; and (4) an ester group. The substituted-evodiamine compounds of the invention have good anti-tumor activities for various tumor cells, provide a new way for deep research and development of new anti-tumor medicaments and can be used for preparing new anti-tumor medicaments.

The invention relates to the field of biotechnologies, and provides a construction method for a sialidase gene knockout mouse model and application thereof. An in vitro and vivo targeted mouse genomeNPL is used for genetically recombining a CRISPR knockout plasmid vector, and a diploid double-knockout NPL mouse knockout model is successfully constructed through an oosperm microinjection technology. The NPL has the important function in a pathophysiological process of a body. Vicious transformation of a cancer cell is always along with overexpression of sialic acid. Now, the overexpression ofthe sialic acid has become one of important markers of the malignant transformation and transferring of a tumor. The model is capable of constructing a new research platform for researching a processof cell canceration, beneficial to a key step of researching generation and transferring of the tumor, and providing a foundation for the research and development of a novel anti-tumor drug.

The invention relates to a dual-sensitivity amphiphilic polysaccharide-doxorubicin conjugate.According to the conjugate, hydrophobic antitumor drug doxorubicin is introduced in a polysaccharide framework through a connecting arm containing a disulfide bond and a hydrazone bond, so that the polysaccharide-doxorubicin conjugate has an amphiphilic property, can be self-assembled into a nano-micelle in water and directly used for tumor treatment, and can also be physically loaded with an antitumor drug to be used for antitumor treatment.The conjugate is mainly characterized in that after the nano-micelle reaches a focus, the disulfide bond in the connecting arm can be degraded specifically by high-concentration reduction substances in focus cells, and meanwhile the hydrazone bond in the connecting arm can be degraded in a special pH environment of the focus, so that the micelle is degraded, the drug is quickly released, and the treatment effect is improved; the antitumor drug is loaded in two modes of chemical conjugation and physical package, and therefore the joint treatment effect is achieved.The polysaccharide conjugate and a pharmaceutical composition can be used for injection or oral administration or external administration, can remarkably improve antitumor activity, and provides a new thought for development of the antitumor drug.

The invention relates to a hyaluronic-acid-based double-targeting nano-composite medicament and a preparation method thereof. Hydrophobic group ursodeoxycholic acid is included in a hyaluronic acid nano-polymer structure and can form an amphipathic polymer and automatically generate micelles in an aqueous solution, and polyethylene glycol can be introduced into the micelles to improve the dispersity and stability of a composite. An anti-tumor medicament can enter a nano-carrier through electrostatic adsorption or physical inclusion to generate a nano-medicament composite, wherein the nano-medicament composite is selectively concentrated in a tumor cell under an active targeting effect of hyaluronic acid and a surface CD44 receptor of a tumor cell, and promotes a tumor tissue to absorb the nano medicament-carrying composite by using a passive osmotic accumulation effect (EPR) at the same time. After an anti-tumor medicament is wrapped by a modified hyaluronic acid polymer, the anti-tumor medicament has the advantages of improving the bioavailability of the medicament, improving the targeting property, reducing the toxic and side effects, prolonging the half-life period of the medicament, being stably stored and the like, so that the tumor targeting therapy efficiency is improved in many ways.

The invention provides a gene, recombinant plasmid and polypeptide for an anti-tumor binary polypeptide. The gene of the recombinant anti-tumor binary polypeptide is obtained by connecting in an operable way the gene of a coding antibody simulator with a recombinant bacillus anthraci protein antigen gene. The recombinant plasmid of the invention is formed by inserting the gene of the coding antibody simulator by double-chain oligomeric nucleotide directed mutagenesis method into the recombinant bacillus anthraci protein antigen gene. The obtained recombinant plasmid is infected into engineering bacillus coli BL-21 to get engineering bacillus coli cell of anti-tumor binary polypeptide; the anti-tumor binary polypeptide can be obtained by expanding the bacillus coli, settling in centrifugal way the bacillus coli body, crushing in altrasonic way, settling and crushing bacillus coli body by hi-speed centrifuging and treating the upper clean solution. The anti-tumor binary polypeptide is of special targeting characteristic, higher efficiency in killing special physical tumor than prior anti-tumor medicine, and will not attack normal cells, and has much lower toxicity and poor-reaction than prior anti-tumor medicine.