127 results about "Drug toxicity" patented technology

Described herein are compositions, systems, and methods for targeted and controlled drug release. In some embodiments, the compositions, systems, and methods may comprise magnetoelectric silica nanoparticles for targeted and controlled release of chemotherapeutic drugs for cancer treatment. In some embodiments, an external magnetic field may be used to release one or more drugs from the magnetoelectric silica nanoparticles. The disclosed compositions, systems, and methods may improve drug targeting and reduce systemic drug toxicity.

The invention relates to the technical field of biological medicine, in particular to application of a combination of a Cd1 and Mdr1 double-target inhibitor and an azole drug in preparation of an antifungal drug. Based on the fact that the compound as shown in the formula (I) can be used as a CCd1 and Mdr1 double-target inhibitor, the inhibition effect of the compound on candida albicans, candida auricula, candida glabrata, candida tropicalis, trichophyton rubrum and trichophyton indicus when the compound is combined with azole drugs is further evaluated, and the result shows that the compound as shown in the formula (I) has no obvious antibacterial activity on various fungi, and can be used for preparing a medicine for treating various fungi. The drug resistance of CCd1 and Mdr1 overexpression drug-resistant fungi can be reversed, the activity of Candida albicans, Candida auricula, Candida glabrata, Candida tropicalis, Trichophyton rubrum and Trichophyton indicus can be synergistically inhibited when the drug is combined with azole drugs, the treatment dosage of the azole drugs is effectively reduced, and the drug toxicity is small. Therefore, the compound shown in the formula (I) can improve the antifungal effect of azole drugs and reduce the drug resistance of the azole drugs.

The invention discloses a bacteriophage lyase and application thereof, and particularly relates to a bacteriophage lyase with an amino acid sequence as shown in SEQ INNO.2. The bacteriophage lyase can inhibit the growth of escherichia coli, staphylococcus and salmonella, can be used as an antibacterial substance in splitting gram-negative bacteria and can be used for preparing drugs for resisting gram-negative bacteria. The lyase can be used independently or compounded with other substances, the use concentration of antibiotics can be reduced by combining the lyase with the antibiotics, toxic and side effects (such as renal toxicity of polymyxin) of drugs are reduced, and meanwhile, generation of bacterial drug resistance is delayed. After the lyase and the chitosan are combined for use, remarkable antibacterial activity is generated, the antibacterial effect can be achieved without pre-treatment on bacteria, and the practicability is improved.

The invention discloses a novel compound rapid surface anesthetic and a preparation method thereof, and belongs to the field of pharmaceutical preparations. According to the anesthetic, core anesthetic components of lidocaine and tetracaine are compounded with propylene glycol-laurocapram synergistic penetration enhancer, menthol auxiliary penetration enhancer, carbomer 980 gel matrix, triethanolamine pH regulator, glycerol humectant, panthenol soothing agent, purified water and the like, a surface smearing agent is prepared through a specific process, and the anesthetic can be administered in combination with an iontophoresis technology. Compared with the existing surface anesthetic for the cosmetic surgery, the surface anesthetic disclosed by the invention solves the problems of slow effect taking and poor effect, can realize rapid penetration of local skin, has short anesthesia effect taking time, long duration and good effect, has no obvious irritation to the skin, has good product stability, can effectively reduce the drug toxicity, and has a good application prospect. The device is suitable for surface anesthesia of non-surgical medical beauty items such as skin beauty, laser treatment and water-light micro-needles.

The invention relates to the technical field of traditional Chinese medicines, and provides a traditional Chinese medicine composition for treating Parkinson's disease, namely tremor syndrome of traditional Chinese medicine, which comprises the following raw materials by weight: 390-470g of liver calming and wind calming medicine, 140-160g of radix rehmanniae, 280-320g of radix paeoniae alba, 840-960g of first decoction medicine, 390-450g of blood activating and qi regulating and tendon and collateral dredging medicine, and 305-355g of antidote. The traditional Chinese medicine composition has remarkable effects of relaxing tendons and detoxifying, and calming endogenous wind and arresting fibrillation, can play a role in solving the problems of head shaking, limb tremor, muscle stiffness, dyskinesia and the like caused by liver wind internal movement and kidney deficiency and toxic damage of Parkinson's disease, and can nourish liver and kidney, relieve tendon and vessel contracture and relieve pain due to the synergistic effect of various traditional Chinese medicinal materials contained in the traditional Chinese medicine composition. The traditional Chinese medicine composition is especially suitable for Parkinson patients with liver-wind internal movement and kidney deficiency and toxicity loss, and can gradually improve the neurotransmitter level in the brain after being taken. The traditional Chinese medicine composition has an outstanding detoxification effect, can effectively remove accumulation of pathological products such as phlegm and blood stasis in the body of the Parkinson's disease patient, prevents phlegm and blood stasis from generating toxins, and can relieve medicine poison generated by long-term medicine taking of the patient.

The invention relates to a cellulose-based hydrogel prepared based on a cellulose copolymer, a cellulose derivative copolymer or a blend thereof, ultramicro fibers of cellulose form a net structure, and the cellulose-based hydrogel has a highly-ordered three-dimensional micro-nano structure, is better in transparency and is more beneficial to observation of a cell state. The cellulose-based hydrogel is suitable for culture of 3D cell culture tissues and organoids, the stem cells cultured by the cellulose-based hydrogel can form cluster culture stem cells and organoids, the operation is simple, compact fused monolayer endoderm cells are formed, non-directional differentiation of the stem cells can be inhibited, and the formed organoids are thick in vesicle wall and are in a solid shape. And the obtained product is a differentiated mature organ and can be used for high-throughput drug screening, drug toxicity testing and regenerative medicine.

The present invention relates to an antibody-drug conjugate represented by formula (I) having an oxacycloalkyl-substituted camptothecin derivative as a drug toxic moiety, wherein the definitions of each group in the formula are as described in the specification, and the antibody-drug conjugate has a significant antitumor effect. [Formula 1] JPEG2026502963000098.jpg54170

The present invention belongs to the field of biomedical materials and specifically relates to anti-tumor nanoparticles, their preparation methods, and applications. The present invention claims protection for an anti-tumor nanoparticle comprising compound PTe N25, wherein the nanoparticles are simultaneously encapsulated with a camptothecin compound and compound PTe N25 using a phospholipid. The structural formula of compound PTe N25 is: #imgabs0# The present invention utilizes cRGD and camptothecin compounds in conjunction with an organic conjugated polymer material to prepare a dual-targeted chemotherapy-photothermal therapy combined treatment system. This system achieves cRGD-targeted recognition of cancer cells, controlled drug release responsive to spatiotemporal light dual stimulation in the context of a diseased environment, and integrated chemotherapy and photothermal therapy synergistic treatment, significantly reducing drug toxicity and side effects while maintaining anti-tumor efficacy.

The invention relates to an ROS (reactive oxygen species) response type nano prodrug based on dynamic differentiation of monocytes as well as a preparation method and application of the ROS response type nano prodrug. According to the preparation method, citral and captopril react to form a captopril-citral prodrug molecule (Citopril) through a thioketal bond, and then the prodrug molecule and polyethylene glycol lipid are self-assembled in a water-containing solvent, so that the ROS response type nano prodrug (Citopp-NM) capable of being efficiently taken in by blood monocytes is prepared. According to the nano prodrug, dynamic differentiation of mononuclear cells is fully utilized, a nano drug delivery strategy of the mononuclear cells and the ROS responsive activation characteristic of the nano prodrug are combined, more efficient enrichment of the nano prodrug in AS plaques is achieved, activation of the nano prodrug is controlled through differentiation of the mononuclear cells, and the nano prodrug has a good application prospect. Therefore, distribution and activation of drugs in normal tissues can be reduced, the drug effect is improved, and toxic and side effects of the drugs are reduced.

The present application relates to the technical field of health care products, in particular to a pelvic floor muscle repairing composition containing supermolecular tightening Dropsordry and a preparation method thereof, which comprises the following components in mass fraction: 10-14 parts of protein composition, 20-24 parts of chitosan modified Dropsordry, 5-7 parts of freeze-dried powder of Lactobacillus bulgaricus, 10-12 parts of hyaluronic acid, 6-8 parts of glycine and 15-17 parts of proline; each part of the protein composition comprises 20-30 parts of myosin, 30-34 parts of actin, 5-10 parts of hydrolyzed collagen and 240-280 parts of deionized water. The pelvic floor muscle repairing composition can reduce drug toxicity, reduce the amount of drug administration, continuously supplement the required elements of the body during treatment, and quickly relieve the constipation problem caused by the functional damage of the pelvic floor muscle.

Disclosed are an antigen-binding protein targeting PD-L1 and CD40, preparation therefor, and use thereof. The antigen-binding protein targeting PD-L1 and CD40, by means of blocking a PD-1 / PD-L1 inhibitory signaling pathway, acting on an activated CD40 receptor, and simultaneously activating an antigen-presenting cell and a lymphocyte, achieves a significant synergistic anti-tumor effect; meanwhile, the activation of the antigen-binding protein targeting PD-L1 and CD40 on an immune cell only occurs at a tumor microenvironment site, so that problems of systemic drug toxicity and side effects are significantly solved, which enables the antigen-binding protein targeting PD-L1 and CD40 to exert an excellent anti-tumor efficacy under very safe conditions.

To provide, in one embodiment, a method of using human-induced pluripotent stem cells to generate three-dimensional human organ tissue for therapeutic drug toxicity and discovery.SOLUTION: In one embodiment, a high throughput microtiter plate is loaded with both wild type and Rett disease 3D spheroids and exposed to a drug library, and activity is measured and analyzed for disease rescue to wild type cell behavior.SELECTED DRAWING: None

The present application relates to providing a doxorubicin-loaded anti-tumor hemostatic microsphere constructed by a simple, safe and low-cost method and its preparation and application, the doxorubicin-loaded anti-tumor hemostatic microsphere comprises alginate, hemostatic component A, doxorubicin or doxorubicin liposome, crosslinking agent, the hemostatic component A is selected from one or more of carboxymethyl chitosan, hyaluronic acid, collagen, silk fibroin, solve the practical pain point problems such as easy bleeding in tumor resection surgery, large toxicity of chemotherapeutic drugs, large drug dose, frequent drug administration, etc., realize rapid hemostasis in operation, postoperative precise targeted drug delivery, reduce toxic side effects, long-acting drug sustained release, at the same time, all components of the system are safe and reliable, and have good biocompatibility.

The invention relates to the technical field of medicine, and discloses a raltitrexed composition and a preparation method thereof.The raltitrexed composition is prepared by taking a full-biodegradable amphiphilic polymer grafted with hydrophilic chitosan and hydrophobic polylactic acid as a carrier, a raltitrexed drug is embedded in a micelle core of a copolymer by virtue of the large specific surface area and strong adsorption capacity of the carbon nano tube, the targeting function of folic acid and the hydrophobicity of a long chain of polylactic acid under the action of pi-pi action and electrostatic adsorption with the carbon nano tube and chitosan in the composition, so that the encapsulation efficiency is greatly improved; raltitrexed molecules contain elements such as O, N and S, hydrogen bonds can be easily formed by the Raltitrexed molecules and the amphiphilic copolymer, the drug release time can be prolonged through a hydrophobic end polylactic acid side chain, the purpose of slow release is achieved, drug toxicity and adverse reactions are reduced, and the prepared composition is stable in release and ideal in slow release effect.

The invention discloses a polymer with pH responsiveness and active targeting as well as a preparation method and application of the polymer. The polymer has the following chemical structural formula: # imgabs0 #, in the formula, the value of n is 37, and the value range of m is 20-43. The polymer not only can realize pH responsiveness and active targeting at the same time, but also has good biocompatibility and biodegradability, can be self-assembled in an aqueous medium to form a polymer micelle with a core-shell structure to be used as a targeting carrier of an antitumor drug, and has excellent drug loading performance. Therefore, the active targeting release of the anti-tumor drug is realized, so that the drug toxicity is reduced, and the targeting treatment effect is improved.

The present invention discloses, in one embodiment, a method of using human induced pluripotent stem cells to generate three-dimensional human organ tissue for therapeutic drug toxicity and discovery⋅. In one embodiment, a high throughput microtiter plate is loaded with both wild type and Rett disease 3D spheroids and exposed to a drug library, and activity is measured and analyzed for disease rescue to wild type cell behavior.

The invention discloses a method for activating a copper-indium-sulfur thin film through selenium ions at a low temperature and a solar cell based on the thin film. According to the method, the CuInS2 thin film prepared by spin coating is treated by adopting the selenium ion solution, so that diffusion and distribution of selenium ions in the CuInS2 thin film prepared by spin coating are accurately regulated and controlled, carrier recombination is inhibited, and the CuInS2 thin film which is better in energy band structure, lower in defect state density and better in crystallinity and morphology is obtained; and the solar cell with high efficiency (more than 10.0%) is prepared on the basis. The method disclosed by the invention has the advantages of simplicity in operation, low equipment requirement, low cost, low toxicity of used drugs and small damage of a treatment technology to a thin film structure, overcomes the defects of complicated operation, high equipment requirement, damage to a thin film crystal structure by treatment in a high-temperature environment and the like in the prior art, and opens up a new way for high-performance and low-cost inorganic thin film photovoltaics.

The invention discloses a kidney organoid culture and multifunctional detection integrated micro-fluidic chip, which is characterized in that a first chip (top layer) is provided with six independent cell culture chambers, the bottom is provided with a porous membrane, glomerular cells differentiated by human induced pluripotent stem cells are inoculated, and a blood filtration function is simulated; the second chip (middle layer) is provided with a raw urine-like collecting chamber, and a porous membrane is used for receiving the filtrate and detecting final urine-like components; and the third chip (bottom layer) is inoculated with vascular endothelial cells to simulate renal tubule reabsorption and blood purification processes. According to the invention, glomerular filtration and renal tubule reabsorption full-function chains are coupled, and the limitation of single function simulation is broken through; the parallel culture room supports synchronous drug toxicity testing or disease modeling; a multi-valve dynamic control system can accurately simulate pathological microenvironments such as high glucose and renal toxicity; and in-situ multi-parameter real-time analysis is realized through three paths of detection outlets. The chip provides a highly bionic in-vitro platform for drug screening, diabetic nephropathy mechanism research and kidney injury model construction.

The invention belongs to the technical field of drug toxicity prediction, and particularly relates to a drug toxicity prediction method based on metabolism guidance. The invention aims to guide a prodrug or a non-toxic substance through a metabolism method and consider the toxicity of the prodrug or the non-toxic substance in the metabolic process (for example, the prodrug is converted into an effective component in the metabolic process), so as to predict the potential toxicity of the prodrug or the non-toxic substance. By means of the guidance of metabolism, it is desirable to accurately predict whether or not a prodrug will generate toxicity in the body. In the technical scheme provided by the invention, molecules are learned by using different characterization modes for the molecular map, so that different features under different levels and different segmentation methods can be captured. Through the guidance of the metabolic diagram, the reactants can obtain product-related attributes for explaining the toxicity change generated in the metabolic process of the reactants.

The invention relates to the technical field of traditional Chinese medicine extract fermentation, and provides a microspore ganoderma lucidum immune protein and herba houttuyniae fermentation method for treating AIDS and application of microspore ganoderma lucidum immune protein and herba houttuyniae fermentation method.The microspore ganoderma lucidum immune protein and herba houttuyniae fermentation method comprises the steps that microspore ganoderma lucidum strains and herba houttuyniae fermentation liquor are co-fermented, beta-cyclodextrin-selenocystine of a specially-made additive is combined, and the microspore ganoderma lucidum immune protein is obtained; the problems that in traditional AIDS treatment, latent infection cells are difficult to remove, toxic and side effects of drugs are remarkable, and the reconstruction efficiency of an immune system is low are effectively solved, experiments prove that the fermentation product can activate the immune system, the cell number and the dendritic cell maturity are remarkably improved, and the curative effect is good. Meanwhile, the multi-target antiviral effect is achieved by blocking virus envelope combination, inhibiting reverse transcriptase activity and inducing latent infection cell apoptosis; the anti-oxidation and anti-inflammatory characteristics can reduce the risk of opportunistic infection, reduce the toxic damage of antiviral drugs to liver, kidney and intestinal tracts, and provide a new scheme for comprehensive treatment of AIDS and nutrition support of patients.

The invention relates to the technical field of organoid culture, in particular to a construction method and application of a kidney organoid model. Comprising the following steps: S1, carrying out digestion and flow sorting on renal cortex tissues to obtain renal stem cells; s2, carrying out plane culture on the kidney stem cells to obtain kidney epithelial progenitor cells; s3, performing three-dimensional culture on the renal epithelial progenitor cells to obtain the kidney organ model. According to the method, an adult renal cortex tissue is taken as a starting cell source, a kidney organ model with mature near-end and far-end renal tubule phenotypes is efficiently constructed through an optimized plane amplification and three-dimensional induction culture system, and the formation of kidney organs can be efficiently induced in a short time; the finally obtained kidney organ model can be used for simulating acute kidney injury in vitro, and an efficient tool is provided for kidney disease mechanism research, drug toxicity screening and personalized treatment model construction.

The invention provides siRNA for inhibiting LPA gene expression and a conjugate thereof, the siRNA comprises a positive-sense strand and an antisense strand, the positive-sense strand comprises a nucleotide sequence I, and the antisense strand comprises a nucleotide sequence II; each nucleotide in the nucleotide sequence I and the nucleotide sequence II is modified or unmodified nucleotide; the nucleotide sequence I and the nucleotide sequence II are at least partially reversely complementary to form a double-stranded region; the nucleotide sequence I is basically consistent with a first nucleotide sequence, and the first nucleotide sequence is a nucleotide sequence of which the length is at least 15 nucleotides in mRNA expressed by the LPA gene. The siRNA as well as the conjugate and the pharmaceutical composition thereof provided by the invention have strong inhibitory ability on LPA genes, can significantly reduce the expression quantity of LPA mRNA, and are low in drug toxicity.

The application relates to the technical field of medicines, and discloses a composition of raltitrexed and a preparation method thereof. The composition of raltitrexed is a full-biodegradable amphiphilic polymer with hydrophilic chitosan and hydrophobic polylactic acid grafted as a carrier, and the composition is combined with carbon nanotubes and chitosan through pi-pi interaction and electrostatic adsorption. The carbon nanotubes have a large specific surface area and strong adsorption capacity, the folate has a targeting function, and the polylactic acid long chain has hydrophobicity. The raltitrexed drug is embedded in the micelle core of the copolymer, so that the encapsulation rate is greatly improved. The raltitrexed molecule contains O, N, S and other elements, can easily form a hydrogen bond with the amphiphilic copolymer, the hydrophobic end polylactic acid side chain can prolong the drug release time, achieve the purpose of slow release, reduce the drug toxicity and adverse reactions, the prepared composition is relatively stable in release, and the slow release effect is relatively ideal.

Provided is a method for producing a skin organoid, the method comprising: a step for performing a first culture of a primary skin cell in a first medium with at least one support among an extracellular matrix (ECM) and polyethylene glycol (PEG) to form a first skin organoid; and a step for performing a second culture of the first skin organoid in a second medium. In addition, the present disclosure provides: a skin organoid cultured by the method described above, the skin organoid having a round, spherical, three-dimensional shape and comprising a center portion, which is densely packed with cells, a stratum corneum formed on the outside of the center portion, and a hair root, wherein the cells can move from the center portion to the stratum corneum; and a method for evaluating drug toxicity by using same.

The invention belongs to the technical field of toxicological evaluation, and discloses a photoresponsive liver chip system for evaluating drug immunotoxicity, which comprises a liver chip with a multilayer structure, a photoresponsive immune cell elimination reagent and an illumination device. The invention also discloses an application of the photoresponsive liver chip system in drug immunotoxicity evaluation, which comprises the following steps: firstly, in a state that the photoresponsive immune cell elimination reagent is not activated, performing a first round of toxicity detection on a to-be-detected drug to obtain baseline toxicity data; then, activating a reagent through illumination, and specifically eliminating immune cells in the chip; then carrying out a second round of toxicity detection; the immunotoxicity contribution of the to-be-detected medicine is accurately evaluated by comparing the difference of two rounds of toxicity detection data. The method realizes sequential resolution evaluation on the direct toxicity and the immune-mediated toxicity of the drug on the same biological sample, overcomes the defects that a traditional method is tedious in operation and cannot distinguish toxicity sources, and has the advantages of rapidness, accuracy and high throughput.

This invention provides an siRNA for inhibiting MSTN gene expression, its conjugates, and their applications. The siRNA comprises a sense strand and an antisense strand, wherein the sense strand comprises nucleotide sequence I, and the antisense strand comprises nucleotide sequence II; each nucleotide in nucleotide sequence I and nucleotide sequence II is a modified or unmodified nucleotide. The siRNA, its conjugates, and the pharmaceutical composition provided by this invention exhibit strong inhibitory activity against the MSTN gene, significantly reducing the expression level of MSTN mRNA, and have low drug toxicity.

The invention discloses boron-rich magnetic nanoparticles and a preparation method and application thereof.The boron element content of the boron-rich magnetic nanoparticles is as high as 9-15 wt%, the boron-rich magnetic nanoparticles are prepared through a one-step solvothermal method, an iron oleate precursor, boric acid, phenyl ether and polyethylene glycol dicarboxylic acid are mixed, and then the mixture is subjected to a three-stage temperature programming reaction at the temperature of 90-120 DEG C, 180-220 DEG C and 250-270 DEG C to obtain the boron-rich magnetic nanoparticles; the prepared boron-rich nanoparticles are uniform in particle size and good in dispersity, have both high boron loading and superparamagnetism, and can significantly improve the tumor killing efficiency of BNCT and reduce the drug toxicity; the superparamagnetism can realize active targeting delivery guided by an external magnetic field, and the magnetic resonance imaging contrast agent can be used for avoiding the risk of magnetic agglomeration at the same time; fluorescence labeling and cell membrane or specific cell membrane protein modification are easily performed on the surfaces of the particles, so that the treatment effect is enhanced, and diagnosis and treatment integration guided by multi-modal imaging is realized; the boron-rich nanoparticles are simple and convenient in preparation process and easily available in raw materials, and have wide application prospects in tumor boron neutron capture therapy drugs.

An in vitro construct useful for toxicity testing is provided, comprising: a three-dimensional (3D) scaffold comprising silk fibroin and having a crosslinked porous matrix; and stem cells adherent to the 3D scaffold. In some embodiments, the stem cells adherent to the 3D scaffold maintain stable mitochondrial DNA in long term culture. In some embodiments, the stem cells are urine stem cells.

The invention discloses a tri-hybrid ionic iridium (III) complex containing a diphosphine ligand and an anti-tumor application thereof, and belongs to the technical field of crossing of metal organic complex design and tumor drugs. By introducing a large-rigidity ligand, a traditional two-heteroligand iridium complex is converted into a three-heteroligand complex with a more stable structure, the complex can keep the structure complete in a physiological environment, the drug stability is ensured, in-vivo transmission and absorption are efficient, and the bioavailability is remarkably improved; the compound shows a strong inhibition capability on a plurality of tumor cell lines, the IC50 value is far lower than that of a traditional drug, the toxic effect is excellent, and the universality is strong; the iridium (III) center and the diphosphine ligand in the complex synergistically exert anti-tumor activity to form a'metal-ligand 'synergistic anti-cancer mechanism, and the complex is sensitive to malignant tumor microenvironment, can specifically release iridium ions and overcome tumor drug resistance, provides candidate molecules for development of novel anti-cancer drugs, and has wide application prospects.

The invention relates to the field of animal models, in particular to a method for constructing a chronic tympanic membrane perforation rat model. The construction method comprises the following steps: under a microscope, perforating a rear quadrant of a tympanic membrane of a unilateral ear of a rat, embedding a gelatin sponge into the perforated part for a period of time, and then removing the gelatin sponge to obtain a chronic tympanic membrane perforated rat model; wherein the gelatin sponge is a gelatin sponge infiltrated with a drug solution, and the drug solution is a dexamethasone solution. According to the construction method of the chronic tympanic membrane perforation rat model, the success rate of modeling can be increased on the basis of reducing the death rate of animals, animal waste caused by drug toxicity and the risk of cancerogenic substance exposure of experimenters are reduced, and the construction method has important significance in tympanic membrane perforation research.