51 results about "In vivo toxicity" patented technology

The invention is directed to a polypeptide comprising a human IL-2 mutein numbered in accordance with wild-type IL-2 wherein said human IL-2 is substituted at at least one of positions 20, 88 or 126, whereby said mutein preferentially activates T cells over NK cells. D20H and I, N88G, I, and R, in particular have a relative T cell-differential activity much greater than native IL-2, with predicted associated reduced in vivo toxicity. The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

The invention discloses a preparation method and application of a drug-loaded magnetic composite nanometer material. The fat-soluble solution (or emulsion) of the surface lipophilic magnetic nanoparticles and the drug is added to the dichloromethane solution of polylactic acid/glycolic acid copolymer (PLGA), and the three are mixed with each other to form an oil phase system. The oil phase system is added dropwise to the aqueous solution in which the surfactant Pluronic F127 is dissolved to form an oil-in-water system, and then the drug-loaded magnetic composite nanomaterial is obtained under the action of ultrasound. The drug-loaded magnetic composite nanomaterial can concentrate the drug in the tumor area under the action of an in vitro magnetic field to achieve targeting; the coating of PLGA solves the problem of mutual self-aggregation of magnetic particles, and the slow release control of the drug solves the problem It has great toxicity and side effects in the body and can be quickly taken up by tumor cells, leading to apoptosis of tumor cells and reversing the multidrug resistance of tumor cells.

The invention relates to the field of anti-tumor drugs, and specifically discloses an indole alkaloid adduct, and a preparation method and an application thereof in preparing an anti-tumor drug. The indole alkaloid adduct has a structure shown as a formula I, wherein R is formed in the way that an indole alkaloid is subjected to hydrazinolysis and the hydrazinolysis product is bonded with hydrazine group. The indole alkaloid adduct can significantly reduce toxicity to normal cells and in-vivo toxicity and inhibit in-vitro proliferation of various tumor cell lines and the growth of tumor in the nude mouse bearing the tumor.

The invention is a continuation of the patent CN102499986A ''a macromolecule-cisplatin compound and its preparation method and application'', the content and claim of which are both suitable for the invention. The invention relates to a water-soluble polyglutamic acid-cisplatin compound and provides a preparation method and an application of the compound. The invention belongs to the field of a bio-medical technology. According to the invention, gamma-polyglutamic acid prepared by biological fermentation is used as a raw material, and a small molecular modifier and an active group at the side chain of the gamma-polyglutamic acid react to prepare a gamma-polyglutamic acid derivative; and then, cisplatin reacts with a modified carrier to prepare a drug-loaded compound containing free cisplatin as well as combined cisplatin. Water solubility of the water-soluble polyglutamic acid-cisplatin compound is remarkably enhanced than water solubility of existing cisplatin compounds, and utilization rate of cisplatin is raised. The water-soluble polyglutamic acid-cisplatin compound has a more excellent anti-tumor effect than cisplatin, and toxicity in vivo of the water-soluble polyglutamic acid-cisplatin compound is obviously reduced.

A large number of aziridinyl quinones represented by Series 1-9 were studied with respect to their DT-diaphorase substrate activity, DNA reductive alkylation, cytostatic/cytotoxic activity, and in vivo activity. As a result generalizations have been made with respect with respect to the following: DT-diaphorase substrate design, DT-diaphorase-cytotoxicity QSAR, and DNA reductive alkylating agent design. A saturating relationship exists between the substrate specificity for human recombinant DT-diaphorase and the cytotoxicity in the human H460 non-small-cell lung cancer cell line. The interpretation of this relationship is that reductive activation is no longer rate limiting for substrates with high DT-diaphorase substrate specificities. High DT-diaphorase substrate specificity is not desirable in the indole and cylopent[b]indole systems because of the result is the loss of cancer selectivity along with increased toxicity. We conclude that aziridinyl quinones of this type should possess a substrate specificity (VMAX/KM )<10x10-4 s-1 for DT-diaphorase in order not to be too toxic or nonselective. While some DNA alkylation was required for cytostatic and cytotoxic activity by Series 1-9, too much alkylation results in loss of cancer selectivity as well as increased in vivo toxicity. Indeed, the most lethal compounds are the indole systems with a leaving group in the 3a-position (like the antitumor agent EO-9). We conclude that relatively poor DNA alkylating agents (according to our assay) show the lowest toxicity with the highest antitumor activity.

The invention discloses a cabazitaxel prodrug as well as a preparation method and an application thereof. A structural formula of the prodrug is represented as a formula (I) and the prodrug is prepared from cabazitaxel and hydrophobic molecules through an esterification reaction. The prodrug has better antitumor activity, can directly release active components in a hydrolytic manner in vivo, and can prevent in-vivo toxicity caused by direct injection of cabazitaxel. The prodrug has better solubility in water and can form nanoparticles in water through self-emulsification; the prodrug can be obtained with a single-step esterification method, is high in yield, low in preparation cost, high in stability and good in safety, meets requirements of clinical medication and large-scale industrial production, and has good market prospect and clinical application value.

The invention relates to the technical field of T cell tumor treatment and in particular relates to a compound containing an anti-PD (Program Death)-1 gene and poly-spermidine and application of the compound to treatment of tumors. The compound contains a polyspermidine polymer and the anti-PD-1 gene at the mass ratio of (1 to 100) : 1. The compound is transfected to a T cell in vitro to prepare a self-secretion anti-PD-1 antibody-T cell and can generate a PD-1 antibody, so as to help to block a PD-1 signal and effectively help a depleted T cell, and promote the T cell capable of resisting tumor immune response to treat the tumors. Compared with the prior art, the secretion anti-PD-1 antibody-T cell provided by the invention can be used for effectively treating the tumors, and immune treatment of the tumors can be realized; an in-vivo toxicity problem does not exist.

The invention discloses rare earth metal complexes using orbifloxacin as a ligand, a method for synthesizing the same and application thereof. In the tests of the inhibiting effect of the complexes on bacteria such as salmonella pullorum, swine streptococcosis and bovine streptococcus uberis, the results show that the complexes have quite high bacteriostatic activity, wherein all of Er(III), Sm(III) and Eu(III) complexes of the orbifloxacin have certain bacteriostatic activity on the swine streptococcosis which cannot be inhibited by orbifloxacin and doxycycline. Mouse acute toxicity tests show that the complexes have low in-vivo toxicity to mice and are highly tolerable to mice. The toxicity of various complexes meets the acute oral toxicity ungraded standards of European Community and the PRC food security assessment grade-two (actually non-toxic) standard, wherein the neodymium complex of the orbifloxacin has the lowest toxicity.

The invention discloses a modified polyethyleneimine derivative as well as a synthesis method and application thereof. According to the invention, Triton X-100 is conjugated to polyethyleneimine, suchthat a PEI-Triton-N carrier is obtained. In-vitro cell evaluation shows that the carrier shows good safety and stability; cell transfection effect experiments show that the carrier shows efficient and low-toxicity gene delivery capacity, can significantly improve the gene transfection efficiency of various cells including skin immortalized cells HaCaT difficult to transfect, and is an excellent in-vitro transfection reagent; an in-vivo toxicity experiment shows that the carrier has no obvious systemic toxicity; and a gene delivery experiment result of mouse skin local administration shows that the carrier has good local administration gene delivery capability and is a good local administration gene delivery vector.

The present invention relates to a modified CpG oligodeoxynucleotide (ODN) which is prepared by coupling a consecutive sequence of deoxyribothymine (dT) to the 3′-terminus of CpG ODN having immunoregularory function, thereby improving immunoactivity of splenocytes, macrophages and peripheral mononuclear cells, and therefore, can be effectively used as a vaccine adjuvant for preventing and treating hepatitis B or an anti-cancer agent. Since the phosphorothioate CpG ODN having the consecutive sequence of dT at its 3′-terminus shows high activity inducing Th-1 immune response and does not elicit in vivo toxicity with guaranteeing its safety, it can be effectively used as a vaccine adjuvant.

The invention discloses a method for screening probiotics. The method comprises the following steps of: (1) carrying out a primary culture on spleen tissues of a pig or a domestic animal; (2) attacking toxicity of the tissues through colon bacillus K88, and testing variations of levels of an interleukin 8 and an interleukin 4; (3) respectively processing the tissues through candidate probiotic strains, and testing variations of levels of two interleukins; (4) comparing the variations to select probiotic strains which are similar in variation degrees of the two interleukins but opposite in effect due to treatment of the colon bacillus K88; and (5) through the colon bacillus K88 animal toxicity attacking test, observing protecting effects of primarily selected probiotic strains, and finally determining an efficient probiotic strain. The method for screening the probiotic disclosed by the invention has the remarkable advantages that: the method combining in vitro immunology experiment and in vivo toxicity attacking experiment is high in accuracy, strong in pertinency and time-saving; and the screened probiotics can effectively replace antibiotic, and greatly reduce diseases caused by colon bacillus so as to promote the health of the animal.

The invention relates to the technical field of cancer treatment by T cell, and particularly relates to a composite containing anti-PD-1 gene and polycation and its application in treating tumor; the composite includes poly-cationic polymer and anti PD-1 gene in the mass ratio of 1-100: 1. The composite is transfected to the T cell externally, and the secretion anti OD-1 antibody-T cell is prepared, and PD-1 antibody can be generated, thus helping to stop the PD-1 signal, effectively helping the exhausted T cell, and promoting the T cell treatment cancer of antitumor immunity response. Compared with the prior art, the secretion anti OD-1 antibody-T cell can effectively treat tumor and realize the tumor immunological therapy; besides, the composite is free from in-vivo toxicity.

The invention relates to the technical field of drugs for treating angiogenesis, in particular to a poly spermine polymer-contained nano-particle for treating angiogenesis, and a preparation method and application of the nano-particle. The poly spermine polymer-contained nano-particle comprises a poly spermine polymer and a genetic material, wherein the mass ratio of the poly spermine polymer to the genetic material is (1-100): 1. Compared with the prior art, the nano-particle provided by the invention can effectively inhibit angiogenesis, can realize the delivery of genetic material, can avoid problems of in vivo toxicity and in vivo immunogenicity, can avoid adhesion of in vivo non-target tissues as the nano-particle is uncharged, can realize targeting of in vivo diseased cells so as to effectively improve the targeting effect, and does not affect the endocytosis of the in vivo diseased cells.

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 relates to the technical field of medicines for treating vascular proliferation and in particular relates to a polycationic nucleic acid compound for treating vascular proliferation as well as a preparation method and application thereof. According to the polycationic nucleic acid compound nano-particles for treating vascular proliferation disclosed by the invention, the nano-particles comprise polycationic nucleic acid materials and genetic substances, wherein a mass ratio of the polycationic nucleic acid materials to genetic substances is (1-100):1. The polycationic nucleic acid compound nano-particles for treating vascular proliferation comprise the polycationic nucleic acid materials and the genetic substances. Compared with the prior art, the nano-particles can effectively inhibit vascular proliferation and realize delivery of the genetic substances, and the problems of in-vivo toxicity and in-vivo immunogenicity are solved. Moreover, because the nano-particles are neutrally charged, adhesion of in-vivo non-target tissues can be avoided, and in-vivo pathological cell targeting is realized, so that the targeting effect is effectively improved, and endocytosis of in-vivo pathological cells is not influenced.

A sorbic acid-tea polyphenol composite nanoparticle and application thereof, the invention relates to the technical field of nanocomposite particle synthesis; its preparation method is as follows: 1. preparing composite nanoparticle; 2. detecting the encapsulation efficiency and Drug loading, the prepared composite nanoparticles have been tested for functional response performance, and qualified composite nanoparticles have been obtained; 3. Safety performance testing of composite nanoparticles: starting from the overall safety of composite nanoparticles, through the hemolytic test , In vitro cytotoxicity test and mouse acute toxicity test to study the in vitro and in vivo toxicity of composite nanoparticles, to initially understand the intensity and nature of their toxicity, and to obtain the dose-effect relationship; 4. Apply composite nanoparticles to the development of fresh-keeping health care. The safety performance of the composite nanoparticles is guaranteed, which provides an important guarantee for later application, and has a wide range of applications, providing a new application for the existing fresh-keeping health care field.

The invention relates to an acid-responsive mesoporous silica nano-based drug as well as a preparation method and application thereof. The nano-based drug takes mesoporous silica nanoparticles as carriers, acid-responsive functional molecules are coupled on the mesoporous silica nanoparticles, a drug is coupled on the acid-responsive functional molecules, and a drug made from dopamine and used forvascular normalization is used. The acid-responsive mesoporous silica nano-based drug can stably exist during in vivo transportation, pH response can be realized when the drug reaches weakly acidic tumor sites, and the drug made from the dopamine and used for prompting the vascular normalization is released, thereby achieving the effects of reducing in vivo toxicity, improving biological safety and obviously prompting the normalization of in situ tumor vessels. Furthermore, the preparation method of the acid-responsive mesoporous silica nano-based drug is simple and easy to operate, high in stability and high in repetition rate.

The invention belongs to the technical field of medicinal chemistry, and relates to a metal beta-lactamase inhibitor pyridine dicarboxylic acid amine derivative, a preparation method thereof and an application thereof in the antibacterial field. The derivative has the following structural formula: the compound has better inhibition activity on metal beta-lactamase (NDM-1, IMP-4 and VIM-1), and can recover the antibacterial activity of engineering strains for producing metal beta-lactamase and clinically separated enterobacteriaceae bacteria on carbapenem antibiotics; and the drug effect of meropenem on carbapenem-resistant Escherichia coli (NDM-1-producing metal beta-lactamase) can be improved by at least 1024 times to the maximum extent. The compound 1 and meropenem are combined for use, so that strains capable of producing MBL can be quickly killed. A compound toxicity experiment proves that the compound has very small in-vitro cytotoxicity and in-vivo toxicity, and a mouse in-vivo experiment shows that the survival rate of a mouse infected with metal-producing beta-lactamase klebsiella pneumoniae can be remarkably improved through combined treatment of the compound and meropenem. The product can be used as a candidate drug of a novel metal beta-lactamase inhibitor.

The invention relates to the technical field of tumor treatment, and discloses a novel medicine for treating tumors, and the medicine is mainly prepared from the following components in percentage by weight: 15 to 30 percent of astragalus membranaceus, 10 to 20 percent of ganoderma lucidum, 10 to 60 percent of oldenlandia diffusa and 15 to 30 percent of sculellaria barbata. According to the novel medicine for treating tumors, astragalus membranaceus and ganoderma lucidum are used as main medicines, so that the effects of strengthening body resistance, tonifying yin, enhancing organism immunity and inhibiting virus breeding and growth are achieved; oldenlandia diffusa, sculellaria barbata, honeysuckle, coptis chinensis, dried toad skin and rabdosia rubescens are used as adjuvants, so the traditional Chinese medicine composition has the effects of eliminating evil and resisting cancer, attacking hard mass and removing stasis, promoting blood circulation and removing blood stasis, clearing away heat and toxic materials, tonifying yin and nourishing blood, softening and moistening tendons and vessels, and promoting spleen to remove stasis; salvia miltiorrhiza has the functions of clearing away heat and toxic materials, tonifying spleen and qi and regulating the drug effect, a plurality of drugs are all taken from natural plants and animal bodies, the toxicity and adverse reaction are far lower than those of traditional chemoradiotherapy drugs, and when the two drugs are used together, the drug is expected to become a substitute drug or an important biological drug for cancer treatment.

The invention provides a method for enhancing streptomyces genome editing efficiency and application of the method. By adding an element for controlling Cas9 activity, triple control of Cas9 protein activity on transcription, translation and protein levels is realized, cytotoxicity of Cas9 protein to streptomycete is inhibited, transformation efficiency of plasmids in streptomycete is improved, and efficient gene editing can be realized under induction conditions. According to the invention, a gene editing system which is induced by chemical small molecules and regulated and controlled by inhibitory proteins is established, in-vivo toxicity of Cas9 is inhibited, and efficient introduction of genetic elements and efficient editing of subsequent genes are realized on the premise of not influencing transformation efficiency of editing plasmids and growth and metabolism of host cells. The small molecule chemical inducer is convenient to add, and efficient and accurate genome editing based on double-strand breakage and directional repair can be achieved. The method of the inventioon can be applied to gene engineering and genetic modification transformation of streptomycetes including mode or industrial streptomycetes.

The invention discloses a preparation method of a chemotherapeutic drug nanoparticle-iodophol hyperstable homogeneous embolization agent, which comprises the following steps: (1) dissolving a drug in a low-boiling-point solvent to obtain a drug solution; (2) pressurizing a reaction kettle to 8-12MPa, pumping the medicine solution obtained in the step (1) into the reaction kettle to react for 0.4-1.5 hours after the temperature and the pressure are stable, then removing the low-boiling-point solvent through CO2 pressure relief, then reducing pressure to remove CO2, and collecting to obtain the medicine nanoparticles; and (3) mixing the drug nanoparticles with the iodophol injection, and performing water bath ultrasonic dispersion to obtain the chemotherapeutic drug nanoparticle-iodophol hyperstable homogeneous embolization agent. The preparation process is a pure physical process, other cosolvents, emulsions or other reagents possibly causing in-vivo toxicity are not introduced in the preparation process, and the pure drug nanoparticles have controllable forms and do not change performance.