63results about How to "Small toxicity" patented technology

The present invention relates to a composition of aliphatic emulsion preparation for malignant thoracicoabdominal hydrops and its preparation method. It is made up by adopting pure natural anticancer medicine elemene and at least one polysaccharide selected from ginseng polysaccharide, astragalus polysaccharide, acanthopanax polysaccharide and lyceum polysaccharide as raw material. Said invention can obviously raise solubility of medicine, increase stability of medicine, effectively remove and kill cancer cells and raise immunity of body.

The application discloses a sensitized ferroptosis lipid nano regulator and a preparation method and application thereof, and belongs to the technical field of new adjuvants and new dosage forms of drug preparation combined treatment. The lipid nano regulator is co-assembled by a GPX4 inhibitor and a FASN inhibitor through intermolecular forces, and is modified with an oxidation-reduction sensitive PEG modifier, a molar ratio of the GPX4 inhibitor and the FASN inhibitor is 10:1-1:10, a mass ratio of the sum of the GPX4 inhibitor and the FASN inhibitor to the PEG modifier is 10:90-90:10, and the intermolecular forces include pi-pi stacking force, hydrophobic force and hydrogen bond. The co-assembled nano preparation provides a new strategy and more choices for the development of drug delivery, and meets the urgent needs of high-efficiency and diverse ferroptosis treatment strategies in preparations in the clinic.

The application discloses a 3-(5-(aminomethyl)-1-oxoisoindoline-2-yl)piperidine-2,6-dione derivative and a synthesis method and application thereof, and relates to a 3-(5-(aminomethyl)-1-oxoisoindoline-2-yl)piperidine-2,6-dione derivative which is a compound with the following general formula (I): wherein R1 is selected from,,,,,,,,, and R2 is selected from,,, and. The compound can significantly inhibit the proliferation of leukemia, multiple myeloma, lymphoma, breast cancer, liver cancer and the like at a low dose (nanomole), can effectively degrade IKZF1, IKZF3, BRD4, GSPT1 and CK1 alpha, and has the prospect of being developed into an anti-tumor drug. The application solves the problem that the existing malignant hematological disease treatment drugs have a high safety risk.

The invention belongs to the field of biological medicine, and discloses a chicoric acid (CA)-loaded tetrahedral framework nucleic acid (tFNA) nano preparation for treating acute gouty arthritis. According to the preparation, tFNA formed by self-assembly is taken as a carrier, and a natural active ingredient CA is loaded to form a CA-tFNA compound. The compound overcomes the defects that CA is poor in water solubility and low in bioavailability, and existing drugs are weak in targeting and large in side effect. Through the targeted delivery and synergistic effect of tFNA, the preparation can be effectively enriched in inflammatory joints, significantly inhibit NF-kappa B signal pathways, and down-regulate the expression of key proinflammatory factors such as TNF-alpha and IL-1beta, so that joint swelling and synovial tissue damage are relieved, and repair is promoted. Experiments show that the traditional Chinese medicine composition is remarkable in curative effect and good in safety, and a novel efficient treatment strategy is provided for acute gouty arthritis.

The invention relates to the technical field of biological medicines, and discloses hyaluronic acid modified metal coordination albumin nanoparticles as well as a preparation method and application thereof. The hyaluronic acid modified metal coordination albumin nanoparticle comprises a core and a hyaluronic acid shell layer, wherein the core is formed by self-assembly of an albumin-drug compound, poly-L-aspartic acid and ferric ions through coordination, and the hyaluronic acid shell layer is connected to the surface of the core through coordination or adsorption. According to the hyaluronic acid modified metal coordination albumin nanoparticles as well as the preparation method and the application thereof, the preparation method is simple, convenient and rapid, does not need complex covalent modification, is mild in condition and is easy for large-scale production, and the prepared nanoparticles are uniform in particle size, good in stability and high in stability. In addition, due to the fact that the hyaluronic acid is modified on the surface, the active targeting capacity on CD44 receptor high-expression tumor cells is achieved, the enrichment and treatment effects of the medicine on the tumor site are remarkably improved, and the application prospect in preparation of the anti-tumor medicine is wide.

The application provides a pentaethylenehexamine-beta-cyclodextrin grafted folic acid inclusion cannabidiol nanosphere, a preparation method and an application, the method first prepares a pentaethylenehexamine-beta-cyclodextrin grafted folic acid (PEHA-beta-CD-FA) targeting carrier, then cannabidiol (CBD) is mixed with the carrier in an ethanol-water mixed solvent in a certain proportion, a stable inclusion system is formed through ultrasonic-assisted inclusion + room-temperature light-avoiding stirring, and the system is purified through dialysis, freeze-drying or spray-drying, so that the spherical nanoparticles with uniform particle size of about 100 nm are obtained. The application solves the problems that CBD has extremely low water solubility, poor bioavailability and lacks targeted delivery, the obtained nanospheres have folic acid receptor active targeting, pH response drug release, high encapsulation rate and high colloidal stability, can significantly improve the solubility, dissolution rate and in-vivo targeted delivery efficiency of CBD, and are suitable for the fields of anti-inflammatory, neuroprotective and the like drugs, cosmetics and functional foods.

The invention relates to a TME response diagnosis and treatment integrated method based on EPR, and belongs to the technical field of prodrug controllable release. Trityl free radicals and a drug Mel are coupled, and a trityl prodrug is obtained; according to the prodrug, the characteristic that the trityl free radicals tend to tumor enrichment is utilized, under the tumor microenvironment GSH response, the active drug can be released in a traceless mode no matter in an aerobic environment or an anaerobic environment, and the dissociated trityl free radicals can dynamically monitor changes of the oxygen partial pressure, the pH and the sulfydryl concentration of the surrounding environment. The EPR technology is utilized, real-time monitoring of multiple parameters of the tumor microenvironment and targeted controllable release of drugs are achieved, and the advantage of diagnosis and treatment integration is achieved.

A pyrrolopyrimidine or pyrrolopyridine derivative and its medical use. Specifically, the compound has the structure shown in formula I, has good inhibitory effect on focal adhesion kinase (FAK), and can inhibit its related signal pathways, and can be prepared for treating or preventing diseases related to cancer, pulmonary arterial hypertension, pathological angiogenesis, etc., and can be particularly used for treating diseases caused by excessive or abnormal cell proliferation, such as tumors or cancers.

The application relates to the field of biological medicine, and particularly discloses application of a polypeptide in preparation of a specific targeting molecular probe for tumors with DLL3 overexpression. The application finds that a molecular probe prepared from a polypeptide shown in SEQ ID No. 4 can effectively target tumor tissues with DLL3 overexpression, thereby providing application of a polypeptide or a dimer or a multimer thereof in preparation of a specific targeting molecular probe for tumors with DLL3 overexpression, wherein the amino acid sequence of the polypeptide is shown in SEQ ID No. 4. The molecular probe of the application has high imaging precision, good affinity with DLL3, can realize early diagnosis and imaging of tumor tissues, and can also be used for preoperative and intraoperative image navigation, thereby improving the operation accuracy.

The application belongs to the field of regenerative medicine and nano drug delivery system, and particularly relates to a drug-loaded exosome for improving the testosterone secretion capacity of testicular interstitial cells and a preparation method and application thereof. The application links a targeting FATE1 polypeptide to the surface of MSC-derived exosomes by a chemical coupling method, and loads a small molecule compound in the exosomes by electroporation, so as to obtain modified MSC-derived exosomes. The obtained exosomes can obtain the targeting capacity in testicular interstitial cells, and the natural repair capacity of MSC-derived exosomes and the release of small molecule drugs promote the repair of damaged cells, improve the testosterone secretion capacity of testicular interstitial cells, and relieve male erectile dysfunction caused by diseases or aging.

This invention relates to a fat mimic based on micro / nano-sized starch, its preparation method, and its application. The preparation method of the fat mimic includes: S1: providing a potato starch solution with a concentration of 15-20%; S2: adding 35-50 u / g of α-amylase (with an enzyme activity of 10000 u / g) based on the mass of potato starch, and enzymatically hydrolyzing at 85-90℃ for 5-15 min to obtain a potato starch enzymatically hydrolyzed fat mimic with a DE value of 2-3; S3: adjusting the potato starch enzymatically hydrolyzed fat mimic to a concentration of 1-5%, and using dynamic ultra-high pressure microfluidic technology at a pressure of 180-200 MPa for 6-12 cycles of micro-nano-sized potato starch fat mimic to obtain a particle size between 500-700 nm. Compared with enzymatically hydrolyzed fat mimics, the micro-nano-scale potato starch fat mimics prepared in this invention have significantly improved oil retention, emulsification, emulsification stability, sedimentation, and apparent viscosity. This is beneficial for increasing their fat substitution rate in food and developing low-fat or fat-free foods with a more delicate texture and better sensory experience and textural expectations for consumers.

This invention relates to deuterated 3-oxo-2,3-dihydropyridazine-4-carboxamide inhibitors, their preparation methods, and applications. Specifically, the compounds of this invention have the structure shown in formula (I). This invention also discloses the preparation method of the compounds and their use as AhR inhibitors. The compounds of this invention exhibit excellent selective inhibition of AhR and possess better pharmacodynamic and pharmacokinetic properties, as well as lower toxicity.

This invention relates to the field of biomedical technology, specifically disclosing a STING agonist ST-71, its synthesis method, and its applications. ST-71 is obtained by modifying SR-717. The STING agonist ST-71 synthesized in this invention has the characteristics of good antiviral effect, low toxicity and side effects, and cost-effectiveness, and can also inhibit the proliferation of porcine pseudorabies virus.

The application relates to a kind of SN38-fatty alcohol prodrugs and its self-assembly nanoparticles and application, belong to the field of new excipients and new dosage forms of pharmaceutical preparations, and relates to a kind of 7-ethyl-10-hydroxy camptothecin prodrug antitumor preparation, specifically to the construction of SN38-fatty alcohol prodrug and its self-assembly nanoparticles containing the prodrug, and its application as a drug delivery system in the preparation of antitumor drugs.The structure general formula (I) of SN38-fatty alcohol prodrug or its pharmaceutically acceptable salt is as follows: wherein, n, R, X are described in the claims and the specification.The SN38-fatty alcohol prodrug of the application can be self-assembled into nanoparticles, can effectively improve curative effect, reduce its toxic side effect.

This application belongs to the field of traditional Chinese medicine, specifically relating to a spleen-strengthening and blood-activating traditional Chinese medicine preparation that enhances the expression of metallothionein and its uses. This application provides a traditional Chinese medicine composition comprising, by weight, the following raw materials: 1-20 parts jujube, 1-20 parts yam, 1-10 parts Buddha's hand, 1-9 parts Lithospermum erythrorhizon, 1-9 parts corn silk, 1-9 parts lotus leaf, 1-15 parts ginseng leaf, and 1-20 parts hawthorn. This application also provides a traditional Chinese medicine preparation, as well as the uses of the above-mentioned traditional Chinese medicine composition and preparation. The traditional Chinese medicine preparation provided in this application effectively enhances the liver's detoxification, antioxidant, and anti-inflammatory capabilities by increasing the expression of hepatic metallothionein, thereby reducing the probability of liver damage and preventing and delaying the further development of liver diseases.

The invention discloses a muscle anti-aging composition with spermidine combined with a wolfberry aqueous extract and application of the muscle anti-aging composition, and belongs to the technical field of application of bioactive substances. The composition is prepared by compounding spermidine and a Chinese wolfberry aqueous extract according to a specific ratio, and the Chinese wolfberry aqueous extract is prepared by an optimized aqueous extraction process, so that core active ingredients are reserved to a greater extent. The optimal mass ratio of spermidine to the wolfberry aqueous extract is 1: 2. Through a synergistic effect mechanism, the antioxidant capacity of senescent muscle cells is remarkably improved, and the muscle cell oxidative stress and senescence process induced by D-galactose is effectively inhibited. The composition is simple in preparation process and safe in components, can be widely applied to the fields of food, health care products and medicines, and provides a new solution for developing efficient and natural muscle anti-aging products.

The application belongs to the field of new adjuvants and new dosage forms of pharmaceutical preparations, and particularly relates to a type I and type II immunogenic cell death inducer ion pairing engineered nanoassemblies as well as construction and application thereof. The nanoassemblies are composed of type I ICD inducers, type II ICD inducers, hydrophobic auxiliary counterions and amphiphilic lipid ion pairing. The type I ICD inducer is selected from mitoxantrone, doxorubicin, oxaliplatin or cyclophosphamide; the type II ICD inducer is selected from hypericin; and the hydrophobic auxiliary counterion is selected from cholesteryl sodium sulfate, cholic acid, deoxycholic acid, chenodeoxycholic acid, lithocholic acid, glycolcholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, deoxycholic acid lysine derivative, oleanolic acid and ursolic acid. The type I and type II ICD inducers are combined in the application, and have a synergistic tumor treatment effect.

The present application relates to the technical field of biological medicine, in particular to a gemcitabine-indoleamine 2,3-dioxygenase inhibitor conjugate, a prodrug nanomicelle, a preparation method and an application. The conjugate covalently connects gemcitabine and NLG919 through a connecting arm containing a triazole structure, forms an amphiphilic molecule with a hydrophilic-hydrophobic structure, and can self-assemble into stable small-size nanomicelles in an aqueous solution. The nanomicelle has a pH and enzyme dual-responsive drug release property, can improve the stability and delivery efficiency of gemcitabine, promote cell uptake, and enhance the synergistic antitumor effect of chemotherapy and immunomodulation. The present application also provides an application of the nanomicelle in the preparation of an antitumor drug.

The invention provides a nano preparation for preparing a medicine for inhibiting prostatic cancer and a preparation method of the nano preparation, and relates to the technical field of nano medicinal preparations. The nano preparation comprises the following components in parts by mass: traditional Chinese medicine components and a nano carrier, the traditional Chinese medicine component comprises 15-45 parts of a Chinese yam extract, 5-15 parts of a madder extract, 8-20 parts of cuttlebone superfine powder, 10-25 parts of dragon bone superfine powder and 10-25 parts of oyster superfine powder; the nano-carrier comprises 5-20 parts of phospholipid, 2-10 parts of cholesterol, 1-5 parts of fatty acid, 3-15 parts of polyethylene glycol and 1-5 parts of a surfactant. The average particle size of the nano preparation is 80-150 nm, the polydispersity index PDI is smaller than or equal to 0.30, and the encapsulation efficiency is larger than or equal to 75%. According to the invention, active ingredients of traditional Chinese medicines are combined with a nanotechnology, so that the bioavailability and the tumor targeting property are remarkably improved, the pH-responsive release characteristic is achieved, a remarkable inhibition effect on various prostate cancer cell lines is shown, tumor growth can be effectively inhibited, metastasis can be reduced, and a good application prospect is achieved.

This disclosure provides a dimer amino acid compound, a cell division inhibitor comprising the dimer amino acid compound, and a composition comprising the dimer amino acid compound or the cell division inhibitor.

The invention relates to the technical field of novel biological materials, and particularly discloses an active oxygen and lactic acid dual-driven chemotactic nano motor and a preparation method thereof. Comprising lactate oxidase and selenium nanoparticles, the selenium nano-particles are formed by ascorbic acid and sodium selenite through a chemical reduction method, and the surfaces of the selenium nano-particles are modified with polysaccharide for stabilizing the selenium nano-particles; the lactate oxidase is loaded on the selenium nano-particles to form the nano-motor. Lactic acid is specifically consumed by loading lactic acid oxidase on the surface of the selenium nano-motor, due to high selectivity, the nano-motor can perform directional chemotactic movement towards a lactic acid high expression site, and the excellent oxidation resistance of selenium nano-particles can remove active oxygen and avoid oxidative stress damage, so that the lactic acid and the active oxygen are consumed at the same time.

This application relates to the field of natural product chemistry, specifically disclosing a method for extracting triptolide and its application. The extraction method for triptolide includes the following steps: S1, pretreatment: After washing and drying the roots of Tripterygium wilfordii, it is subjected to ultrafine pulverization and plasma treatment to obtain Tripterygium wilfordii powder; S2, enzymatic hydrolysis: After enzymatic hydrolysis of the Tripterygium wilfordii powder, the enzyme is inactivated, centrifuged, concentrated, and dried to obtain crude triptolide; S3, purification: The crude triptolide is purified by high-speed countercurrent chromatography and vacuum dried to obtain refined triptolide. The above extraction method is simple and safe to operate, and the purity and extraction rate of the obtained triptolide are improved. The obtained triptolide can be mixed with total glucosides of paeony, glycyrrhizic acid, papain, poloxamer, xanthan gum, and propylene glycol to prepare a drug for treating rheumatoid arthritis, which has significant efficacy, high safety, and broad clinical application prospects.

This invention relates to a CDK12 / PARP dual-target inhibitor, its preparation method, and its application. The inhibitor has the general structural formula (I). Specifically, it relates to a CDK12 / PARP dual-target inhibitor, its preparation method, and its application. Pharmacodynamic studies have demonstrated that the CDK12 / PARP dual-target inhibitor of this invention has significant anti-tumor efficacy. The CDK12 / PARP dual-target inhibitor comprises substituted compounds having the general formula (I), or their stereoisomers, hydrates, or pharmaceutically acceptable salts. Compared with the prior art, the compound structure of this invention is novel, and experiments show that it has good CDK12 and PARP enzyme inhibitory activity, and can be used to prepare drugs with CDK12 / PARP dual-target anti-tumor activity.

The invention relates to siRNA for inhibiting MARC1 gene expression and siRNA conjugates thereof, a pharmaceutical composition containing the siRNA conjugates and application of the siRNA conjugates and the pharmaceutical composition. Each nucleotide in the siRNA is independently modified or unmodified nucleotide, and the siRNA contains a positive-sense strand and an antisense strand. The siRNA as well as the conjugate and the pharmaceutical composition thereof can be used for effectively treating and / or preventing diseases related to overexpression of the MARC1 gene.

Use of ritonavir in the manufacture of a medicament for the treatment of human cytomegalovirus infection. Ritonavir is used to inhibit replication of the HCMV immediate early phase. By targeting the HCMV immediate early protein 1, it is stifled at an early stage in the initiation of the HCMV viral gene expression program. This mechanism, which acts upstream in the viral life cycle, offers new possibilities for the treatment of HCMV infection.

The invention discloses a novel phase separation peptide for intracellular protein delivery and a synthesis method and application thereof. The structural formula of the novel phase separation peptide is shown in the specification. According to the novel phase separation peptide, coacervate microdroplets are formed through liquid-liquid separation (LLPS) self-assembly, meanwhile, protein can be rapidly collected, and after a coacervate enters cells by bypassing a classical endocytosis way, glutathione (GSH) in the cells triggers dissociation to release the protein.

The application discloses a kind of self-assembly tumor targeting nano microparticles based on amphiphilic camptothecin conjugate, preparation and application.The nanoparticle is obtained by self-assembly of amphiphilic camptothecin conjugate using reverse phase solvent dispersion method, wherein the amphiphilic camptothecin conjugate is obtained by introducing reduction-responsive cleavage bond on camptothecin 20'-OH, and coupling with targeting peptide.The nanoparticle is spherical, with a particle size of 60-70 nm, significantly improving the water solubility of camptothecin.It can effectively release camptothecin under tumor microenvironment, efficiently kill cancer cells, inhibit 3D tumor sphere and in vivo tumor growth, reduce toxic side effects, and has good application potential.

The invention discloses a compound as well as a preparation method and application thereof, and belongs to the technical field of drug delivery systems and tumor targeted therapy. The compound as shown in the formula 1 is novel and unique in structure, can be used as an anti-melanoma prodrug compound, realizes targeted release and collaborative treatment of drugs (Devistat and TPEDCH) under laser irradiation, has a fluorescence imaging function, is used for monitoring the distribution and activation process of the drugs in tumor cells in real time, and has a good application prospect. The traditional Chinese medicine composition has excellent anti-melanoma effect and low toxic and side effects. Formula 1.

This invention discloses an enzyme-sensitive PDC-type PROTAC modified with a human leukemia cell-targeting transmembrane peptide, its preparation method, and its applications, belonging to the field of tumor targeted therapy technology. This PDC-type PROTAC is composed of a hypoxia-inducible factor 1α (HIF-1α) protein fragment linked to imatinib via dodecanoic acid, and further modified with the human leukemia cell-targeting transmembrane peptide Cyclo-C9C-R and the cathepsin B-sensitive sequence GFLG. The modified PDC-type PROTAC can release the original drug under the catalysis of cathepsin B, with minimal impact on THP1 cell viability, but effectively inhibits the proliferation of K562 and KU812 cells, degrades target proteins, induces apoptosis, and affects the cell cycle. This gives the PDC-type PROTAC significant advantages in the preparation of anti-tumor drugs, particularly showing promising application prospects in the development of drugs targeting human chronic myeloid leukemia cells and human peripheral blood basophilic leukemia cells, opening up a new field for PROTAC drug development.

This invention discloses a pH-responsive silk fibroin-doxacin prodrug nanoparticle, its preparation method, and its application. Silkworm cocoons are degummed, dissolved in a lithium bromide aqueous solution, and freeze-dried to obtain regenerated silk fibroin powder. The regenerated silk fibroin powder is then combined with succinic anhydride, a condensing agent, adipic dihydrazide, and doxorubicin hydrochloride, and treated multiple times with a composite solvent to prepare an aqueous solution of the silk fibroin-doxacin covalently bound. This solution is then added dropwise to an antisolvent under stirring to induce self-assembly into nanoparticles. After centrifugation purification and resuspension in water, the product is obtained. This invention completely overcomes the shortcomings of traditional physical encapsulation methods of silk fibroin, which are prone to burst release. The nanoparticles are extremely stable in physiological blood environments and can rapidly break hydrazone bonds for precise drug release in the slightly acidic environment of tumor cell endosomes. The antisolvent granulation mechanism promotes the flipping of unreacted polar groups to the surface, giving the nanoparticles a moderately negative potential and rich active sites, resulting in excellent colloidal stability and deep functionalization potential.