39results about How to "Increase the maximum tolerated dose" patented technology

Methods for the treatment of CNS disorders using combinations of muscarinic activators and inhibitors, and medicaments comprising muscarinic activators and inhibitors.

The invention provides an active targeting type amphipathic polypeptide nano-drug carrier and preparation and application thereof, and belongs to the technical field of biological medicines. According to an amphipathic polypeptide, an alkyl chain serves as the hydrophobic end, a polypeptide chain with active targeting functional and side chain modification fluorescent functional molecules serves as the hydrophilic end, and an anti-tumor drug is wrapped in a hydrophobic cavity of a micelle formed by self-assembling the amphipathic polypeptide. The nano-carrier can actively target tumor cells and enter the tumor cells through receptor-mediated endocytosis, the amphipathic polypeptide and phospholipid molecules have strong interaction, and the phagocytosis of a nano-drug by tumor cells is promoted. In the process, tracing can be conducted through fluorescent imaging of fluorescent functional molecules modified on the polypeptide chain, and the tumor imaging aim is realized. Finally, the anti-tumor drug is slowly released to kill tumor cells and restrain the growth of tumors. The amphipathic polypeptide nano-carrier is free of toxin, high in biocompatibility and remarkable in anti-tumor efficiency, and the tumor diagnosis and treatment can be integrated.

The invention belongs to the technical field of pharmaceutical chemistry and particularly relates to medical use of 7-hydroxy-butylphthalide in preparation of drugs for preventing and/or treating cardiac and cerebral vascular diseases.

The invention provides a panax notoginseng saponin composition and a preparation method and application thereof.The composition is prepared from, by weight, 30-50% of ginsenoside Rg1, 25-40% of ginsenoside Rb1, 7-16% of notoginsenoside R1, 2.7-8% of ginsenoside Re, 0.5-7.0% of ginsenoside Rd, 0.5-2% of ginsenoside Rf, 0.3-2.0% of ginsenoside Rh2, 1-3% of ginsenoside Rc, 0.3-2.5% of ginsenoside Rb3 and 0.5-2.5% of ginsenoside Rg3, wherein ginsenoside Rg1, ginsenoside Rb1 and notoginsenoside R1 account for 70-95% of the total weight of the active components, and the sum of the contents of ginsenoside Rb1 and notoginsenoside R1 is not smaller than 8 times of the content of ginsenoside Rd.Compared with commercially available Xueshuantong injections and Xueshuantong preparations, the panax notoginseng saponin composition has a more obvious arterial and venous thrombosis resistant effect, low toxicity and high safety.

The invention provides a pharmaceutical composition. The pharmaceutical composition comprises the following components: ginsenoside Rb1, ginsenoside Rg1, notoginsenoside R1, ginsenoside Rd, ginsenoside Re, ginsenoside Rf, ginsenoside Rc, ginsenoside Rh1, ginsenoside Rb2 and ginsenoside Rg3. The invention further provides a preparation method of the pharmaceutical composition. The pharmaceutical composition disclosed by the invention has clear components, stable quality, good controllability, acute toxicity, undue toxicity and hemolysis in comparison with panax notoginseng saponins in the prior art. Test results indicate that the pharmaceutical composition disclosed by the invention has high safety and wide clinical application prospect.

Disclosed are potent immuno-DASH inhibitors, and their use in the treatment of cell proliferative diseases.

A Chinese medicine for treating apoplexy and hemicrania is prepared from Chuan-xiong rhizome, Chinese angelica root, ginseng safflower and borneol. Its preparing process is also disclosed. Its advantages are low dosage and high curative effect.

The invention discloses an active targeting type amphiphilic polypeptide composite nano-micelle prodrug as well as preparation and application thereof, and belongs to the technical field of biological medicines. The composite nano-micelle prodrug is obtained by co-assembling a first polypeptide with negative charges and a second polypeptide with positive charges through electrostatic interaction and hydrophilic and hydrophobic effects; the first polypeptide is Lys-AAm-Gly-Arg-Gly-Asp-Ser, wherein AA is aspartic acid or glutamic acid, and m is 1, 2, 3 or 4; the second polypeptide is Cys-BBn, wherein BB is lysine, arginine or histidine, and n is 1, 2, 3 or 4; amino at a N end of the first polypeptide is connected with a hydrophobic alkyl chain, and amino at a lysine side chain of the first polypeptide is connected with a fluorescent molecule; cysteine in the second polypeptide is covalently linked with an anti-tumor drug through sulfydryl. The nano-composite micelle can be actively targeted to tumor cells, and is disassembled after responding to a tumor slightly acidic environment to form a small-size micelle with a size of 20-30 nm, so that deep delivery of the polypeptide anti-tumor prodrug at a tumor part is facilitated.

Provided are filomicelle nanocarrier systems for the controlled transport and bioselective delivery of encapsulatable, cytotoxic active agents contained therein, particularly anticancer agents. Further provided are methods for controlling destabilization of the filomicelle membrane and the resulting hydrolysis-triggered, controlled release of the active agent(s) encapsulated therein by controlling the blend ratio (mol %) of hydrolysable PEO-block copolymer of the hydrophilic component(s) and of the more hydrophobic PEO-block copolymer component(s), wherein bioselective release of the encapsulated cytotoxic agents is distributed intracellularly, and wherein lowered dosage of the drug was delivered to the non-tumor organs. Thus, the filomicelle system offers enhanced tumor-selective biodistribution of a drug, and a reduced toxicity of the encapsulated drug to other organs.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a tetravalent platinum naphthalimide complex, a preparation method and application thereof. The tetravalent platinum naphthalimide complex has good anti-tumor activity, which is better than that of cis-platinum and oxaliplatin, and the tetravalent platinum naphthalimide complex has better stability than bivalent platinum like cis-platinum, carboplatin and oxaliplatin. According to the invention, the naphthalimide modified tetravalent platinum has good targeting performance on tumor cells, high selectivity on tumor cells is improved, and different from a classic divalent platinum drug, the complex provided by the invention regulates and controls subcellular organelles and cell nucleus functionsto reverse drug resistance by targeting a tumor high polyamine microenvironment, and relieves immunosuppression of T cells around tumors at the same time. The complex provided by the invention also solves the problems of poor solubility, tedious clinical compatibility, poor patient immunity in clinical application of chemotherapeutic drugs and the like of previous bivalent platinum antitumor drugs, and has good fat solubility and water solubility.

The invention discloses reduction-responding polyethylene glycol-polycarbonate targeting maytansine prodrug micelle and a preparation method and application thereof. The reduction-responding polyethylene glycol-polycarbonate maytansine prodrug micelle is made by the self-assembly of amphiphilic polyethylene glycol-polycarbonate maytansine prodrug polymer and amphiphilic polyethylene glycol-polycarbonate maytansine prodrug micelle with targeting molecules bonded at its tail end, in a buffer solution; the micelle is 30-150 nanometers in particle size and 2-60% by weight in maytansine loading capacity. The reduction-responding polyethylene glycol-polycarbonate targeting maytansine prodrug micelle provided herein has good targeting property, amphiphilicity and biodegradability and may be prepared into nano drugs, it is possible to significantly improve drug water-solubility, enhance drug stability during cycling, improve pharmacokinetic behavior of the drugs and improve bioavailability of the drugs; the micelle is applicable to the preparation of targeting drugs for treating malignant tumors, such as melanoma.

The invention belongs to the field of medicines, and particularly relates to a propionamide derivative and application thereof in schizophrenia. The propionamide derivative is CY150112-9, and tests show that the in-vitro affinity of the propionamide derivative is similar to that of CY150112. The CY150112-9 has high affinity with 5-HT2A and D2 receptors, the affinity with 5-HT2A is higher than thatof D2 receptors, it is speculated that the CY150112-9 has a certain effect on negative symptoms while positive symptoms are improved, and the CY150112-9 has a low extrapyramidal side reaction. CY150112-9 also has certain affinity to D3 and 5-HT7, and it is speculated that CY150112-9 may have the effect of improving cognition clinically. And the maximum tolerance of CY150112-9 is higher than 112.

The invention relates to the technical field of medicines, in particular to application of Tilorone to prevention/treatment of African swine fever virus infection. The invention relates to application of telolone and salt forms, hydrates, solvates and isotope substitutes thereof in preparation of drugs for preventing or treating African swine fever viruses. The invention has the following advantages: (1) the bioavailability is high, and the half-life period is long; and (2) the maximum tolerance dose is high, the selectivity coefficient is high, and the safety is high. And (3) the activity of preventing/resisting African swine fever virus infection is strong. And (4) the drug delivery modes are multiple, and the application range is wide. And (5) the composition can be combined for use and has a good effect of preventing/treating African swine fever virus infection.

The invention discloses a cabazitaxel oligo/polylactic acid coupled prodrug and a preparation method thereof. The preparation method is characterized in that cabazitaxel and oligo/polylactic acid undergo an esterification reaction under the action of a condensing agent and a catalyst to obtain the cabazitaxel oligo/polylactic acid coupled prodrug. The invention also discloses a cabazitaxel-oligo/polylactic acid coupled prodrug preparation, and a preparation method and an application thereof. The oligo/polylactic acid is covalently coupled with cabazitaxel, so the in vivo release rate of cabazitaxel is can be regulated, the precipitation of cabazitaxel, caused by strong release, is prevented, the in vivo cycle period of the cabazitaxel is prolonged, and the maximum tolerable dose is increased. The oligo/polylactic acid is approved for use by the US FDA and has an excellent application prospect. The cabazitaxel oligo/polylactic acid prodrug and an amphiphilic polymer PEG5k-PLA8k are assembled to form nanoparticles, and the nanoparticles have a passive targeting effect, and are easily retained in the tumor site by the EPR effect in order to greatly reduce the toxic and side effects ofthe drug on normal tissues.

The disclosure includes zinc prodrugs for targeted delivery of therapeutic, diagnostic or imaging agents to β-cells and methods of use therefor. The disclosure also includes targeted delivery of small molecules to β-cells that stabilize and activate CRISPR effector proteins comprising at least one destabilization domain, to enable CRISPR-based genome editing and transcriptional activation or repression in β-cells.