45 results about "Irinotecan" patented technology

The invention belongs to the technical field of nano-medicines and targeted therapy, and particularly relates to a targeted nano-system nano-drug delivery system based on mesoporous polydopamine as well as a preparation method and application thereof, in particular to an N2E4-MPDA-Gem nano-system based on mesoporous polydopamine (MPDA). A targeting nano system based on mesoporous polydopamine comprises mesoporous polydopamine nano particles loaded with pancreatic cancer chemotherapy drugs, targeting molecules N2E4 are combined with the surfaces of the mesoporous polydopamine nano particles, and phenylboronic acid coatings used for controlling drug release are arranged on the surfaces of the mesoporous polydopamine nano particles. The system adopts a modular design, can be compatible with various chemotherapeutic drugs such as oxaliplatin, irinotecan and the like, and can be flexibly coupled with different targeting antibodies such as EGFR (epidermal growth factor receptor), HER2 (human epidermal growth factor receptor) and the like. A standard preparation process and good stability provide reliable guarantee for clinical transformation, and the compound shows an excellent treatment effect in a solid tumor model represented by pancreatic cancer.

In order to facilitate the approval and commercialization of silicasome drug delivery systems (e.g. irinotecan silicasomes) it is necessary to scale up synthesis of the drug-loaded silicasomes. In this regard, it was discovered that the synthesis protocols used for laboratory synthesis of drug-loaded silicasomes (e.g., 500 mg / batch) do not scale to large scale silicasome production, because the resulting products were too heterogeneous for use as pharmaceuticals. Accordingly, new methods are provided herein that effectively afford the large-scale production of mesoporous silica nanoparticles (MSNPs) and lipid bilayer coated MSNPs (silicasomes).

The invention discloses an irinotecan and afatinib maleate co-loaded liposome preparation as well as a preparation method and application thereof, irinotecan and afatinib maleate are taken as effective components of the liposome, and the liposome comprises a liposome carrier, an inner water phase positioned in a liposome membrane and an outer water phase positioned outside the liposome membrane; the irinotecan and the afatinib maleate are encapsulated in the inner water phase; the inner water phase comprises an ammonium salt aqueous solution, and an ammonium salt gradient exists between the inner water phase in the liposome membrane and the outer water phase outside the liposome membrane; the outer water phase is a physiological isotonic solution. According to the present invention, the research results show that the irinotecan and afatinib maleate co-carrying liposome can simultaneously deliver the two drugs with the synergistic ratio into the same tumor cell compared to the irinotecan single drug liposome and the afatinib maleate single drug liposome so as to maximize the synergistic effect of the drugs, and significantly improve the anti-tumor effect;

The present disclosure relates, inter alia, to the combination therapy of an oncolytic adenovirus for the treatment of retinoblastoma, Ewing's sarcoma or neuroblastoma with a topoisomerase I inhibitor or a prodrug thereof, such as topotecan or SN-38, or a prodrug of a topoisomerase inhibitor, such as irinotecan.

The invention discloses an application of pegylated irinotecan in preparation of a medicine for preventing and / or treating triple-negative breast cancer brain metastasis diseases, which is shown by in-vivo imaging observation and lifetime observation of high, medium and low dose groups of pegylated irinotecan with a specific structure. The high-dose group, the medium-dose group and the low-dose group all have a definite anti-tumor effect, bioluminescence signal values are inhibited to different degrees, the lifetime is prolonged, and the lifetime of the high-dose group and the lifetime of the medium-dose group are remarkably longer than that of the NKTR-102 group.

The invention discloses an anti-tumor composition of irinotecan and liquorice extract or liquorice total flavonoids and a metabonomics detection method of the anti-tumor composition of irinotecan and the liquorice extract or the liquorice total flavonoids. The traditional Chinese medicine composition has an adjusting effect on various enteritis indexes such as body weight, disease activity index score, colon length and reduction of inflammatory factors caused by irinotecan, and has an obvious effect of reducing intestinal toxic and side effects of irinotecan. The invention develops a rapid and efficient UPLC-TQ-MS / MS (ultra performance liquid chromatography-tandem mass spectrometry / mass spectrometry) method capable of synchronously detecting. According to the method, the tissue distribution condition of irinotecan and main metabolites thereof in a mouse body can be detected and quantified with high sensitivity, and the influence of liquorice total flavonoids and liquorice total extracts on the metabolic process and distribution characteristics of irinotecan and metabolites thereof is evaluated; not only can the possible effect of the liquorice in the process of reducing irinotecan be revealed, but also a theoretical basis can be provided for optimization of a medicine compatibility scheme.

This disclosure particularly relates to combination therapy of oncolytic adenoviruses with topoisomerase I inhibitors or their prodrugs (such as topotecan or SN-38) or prodrugs of topoisomerase inhibitors (such as irinotecan) for the treatment or prevention of ovarian cancer, cervical cancer, lung cancer, colon or colorectal cancer and / or pancreatic cancer.

The application relates to the technical field of aspirin pharmaceutical chemistry, in particular to an aspirin-sulfonamide hybrid, a preparation method and application thereof. The preparation method can synthesize a plurality of novel aspirin-sulfonamide hybrids by taking piperazine as a bridge, and by a three-step continuous method of "acyl chlorination, sulfonamidation and N-acylation" according to a "molecular hybridization principle". In the process, only one separation and purification is performed, and the preparation steps are simple. The aspirin-sulfonamide hybrid prepared by the method is most effective on human non-small cell lung cancer cells A549, and the activity is more than 33 times higher than that of a parent aspirin, and is similar to the activity of an anticancer drug irinotecan. The aspirin-sulfonamide hybrid 3k prepared by the method has a certain inhibitory effect on various cancer cells. The hybrid can induce human non-small cell lung cancer A549 cell apoptosis in a concentration-dependent manner, and can induce human non-small cell lung cancer A549 cell cycle arrest in the G0 / G1 phase, and inhibit cell growth.

This invention provides an irinotecan-conjugated polypeptide compound, its preparation method, and its application, belonging to the field of biomedical technology. Irinotecan (Dxd) is the active pharmaceutical ingredient. Irinotecan belongs to the topoisomerase I inhibitor class—camptothecin derivatives—and is a semi-synthetic small molecule chemotherapeutic drug capable of directly killing cancer cells in the active division phase and inhibiting tumor growth. TYLCTACDYTHH is a highly effective PDPN-targeting peptide that can effectively target the PDPN site in human glioblastoma. In vitro and in vivo experimental results show that the conjugated compound of this invention can significantly inhibit the proliferation of primary glioblastoma cells and effectively inhibit the growth of intracranial orthotopic xenografts in NOD-SCID mice, demonstrating good anti-tumor activity. This compound shows promise for targeted therapy of glioblastoma and has the potential to prolong patient survival.

The application discloses a kind of endoplasmic reticulum of tumor cell can be targeted N -(2-hydroxypropyl) methacrylamide (HPMA) polymer-drug conjugate. The chemotherapeutic drug carried by the HPMA polymer is at least one of doxorubicin, epirubicin, pirarubicin, cisplatin, oxaliplatin, camptothecin, paclitaxel, gemcitabine, methotrexate, vinblastine, mitoxantrone, irinotecan, and the linker for connecting the drug and the HPMA polymer is at least one of hydrazone bond, amide bond, ester bond, disulfide bond, and ketosulfenyl bond. The HPMA polymer-drug conjugate targets the drug to the endoplasmic reticulum through receptor-ligand interaction, can cause severe endoplasmic reticulum stress, thereby transporting a large amount of calnexin to the tumor cell membrane surface, greatly improving the immunogenicity of tumor cells, and promoting tumor immunotherapy.

The anti-cancer use of a camptothecin derivative which demonstrates a surprising resistance to the degrading effects of Human Serum Albumin ("HSA") in vivo is disclosed. Since HSA represents about half of serum protein in human blood, previous camptothecins generally worked poorly or not at all in vivo due to inactivation by HSA among other factors. Since NSS-01 is similar in mechanism of action to other camptothecins, and as demonstrated herein has both: (i) greater anti-tumor activity against various human cancers and (ii) less toxicity at therapeutic dosing - than topotecan and irinotecan; and without wishing to be bound by theory, NSS-01 demonstrated desirable antitumor activity against adenocarcinomas, it therefore should demonstrate desirable antitumor activity against other cancers that are susceptible to Topoisomerase I inhibitors.

This invention describes methods for treating or ameliorating the symptoms of cancer in a subject with agents, compositions and regimens designed to promote anti-tumor effects and avoid drug resistance effects. Combinations of active agents can be used including agents for inhibiting or suppressing expression of TGF-β2 in combination with an irinotecan-containing agent, regimen or formulation, for example, a FOLFIRINOX agent, a NALIRIFOX agent, an IRIFOX agent, or an IRINOX agent. Biomarkers can be used to select subjects who benefit from such therapeutics.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. In preferred embodiments, the antibody may be an hRS7 antibody. The methods and compostions are of use to treat Trop-2 expressing cancers in human patients, preferably in patients who are resistant to or relapsed from at least one prior anti-cancer therapy, more preferably in patients who are resistant to or relapsed from treatment with irinotecan. The immunoconjugate may be administered at a dosage of 3 mg / kg to 18 mg / kg, preferably 8 to 12 mg / kg, more preferably 8 to 10 mg / kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size and reduce or eliminate metastases. Preferred tumors to treat with the subject immunoconjugates include triple-negative breast cancer, HER+, ER+, progesterone+ breast cancer, metastatic non-small-cell lung cancer, a metastatic small-cell lung cancer and metastatic pancreatic cancer.

The invention belongs to the technical field of medicines, and particularly relates to a preparation method and application of a self-assembled conjugate of a non-steroidal anti-inflammatory drug and irinotecan. Water-insoluble non-steroidal anti-inflammatory drugs (ibuprofen, oxaprozin, naproxen, indometacin and the like) are introduced into a water-soluble anti-tumor drug irinotecan through esterification reaction and are self-assembled into nano particles in an aqueous solution, and then the self-assembled nano conjugate with an anti-tumor effect is formed. The inhibition activity of the nano particles prepared by the method on tumor cells is far better than that of irinotecan and a corresponding physical mixture of a non-steroidal anti-inflammatory drug and irinotecan, cancer cell proliferation can be accurately blocked by synergistically inhibiting protein expression of COX-2 and Topo I, particularly, the inhibition effect on Topo I is better, the anti-tumor treatment effect is greatly improved, and the nano particles have good application prospects. And a more efficient scheme is provided for tumor treatment.

The present invention relates inter alia to aptamers that specifically bind to Irinotecan and methods of using the same.

The application relates to the field of medicine, in particular to the application of 4-hydroxyphenylacetic acid and irinotecan as cancer chemotherapy drugs. In view of the technical defects that the existing irinotecan chemotherapy hepatoprotective drugs have single action and may interfere with the chemotherapy effect, the application provides the application of 4-hydroxyphenylacetic acid and irinotecan in the preparation of cancer chemotherapy drugs. The application has the following advantages: 1. clear hepatoprotective effect: 4HPAA can significantly alleviate the liver fatty degeneration induced by irinotecan; 2. significant synergistic anti-tumor effect: the tumor inhibition effect of the combination of 4HPAA and irinotecan is significantly better than that of the single-drug group; 3. high safety; and 4. great clinical transformation potential.

The invention discloses a microneedle patch with imrecoxib included by modified cyclodextrin as well as a preparation method and application of the microneedle patch, and relates to the technical field of biological medicines. The invention relates to a microneedle patch with imrecoxib included by modified cyclodextrin. The medicament of the microneedle patch is prepared from imrecoxib, crotamiton, carborane-beta-cyclodextrin and water. The carborane-beta-cyclodextrin clathrates imrecoxib and prepares the microneedle patch, so that the water solubility and transdermal efficiency of the fat-soluble drug imrecoxib can be remarkably improved, the first-pass effect and gastrointestinal reaction of oral administration can be avoided, and an efficient and safe local treatment scheme is provided for diseases such as knee osteoarthritis.

This invention describes methods for treating or ameliorating the symptoms of cancer in a subject with agents, compositions and regimens designed to promote anti-tumor effects and avoid drug resistance effects. Combinations of active agents can be used including agents for inhibiting or suppressing expression of TGF-β2 in combination with an irinotecan-containing agent, regimen or formulation, for example, a FOLFIRINOX agent, a NALIRIFOX agent, an IRIFOX agent, or an IRINOX agent. Biomarkers can be used to select subjects who benefit from such therapeutics.

The application discloses application of a pharmaceutical composition with GL-V9 and a chemotherapeutic drug as active ingredients in treatment of tumors, and the GL-V9 can obviously achieve a drug synergistic effect when the GL-V9 is combined with a classical chemotherapeutic drug to treat tumors, and the effect is obviously superior to combination of similar drugs and the chemotherapeutic drug. The chemotherapeutic drugs include PARP1 inhibitors, capecitabine, irinotecan, sorafenib, cisplatin or 5-fluorouracil; and the tumor types include leukemia, colorectal cancer and lung cancer.

The present invention describes a method for treating or improving the symptoms of cancer in subjects with agents, compositions, and regimens designed to promote anti-tumor effects and avoid drug resistance.A combination of active agents can be used, including agents, regimens, or preparations containing irinotecan, such as FOLFIRINOX, NALIRIFOX, IRIFOX, or IRINOX, and agents for inhibiting or suppressing the expression of TGF-β2.Biomarkers can be used to select subjects who will benefit from such therapeutic agents. TIFF2026507184000026.tif117156

Methods of treating, suppressing, or reducing the severity of a liver cancer in a subject are described herein. The disclosed methods include administering to the subject a first amount of safranal or a pharmaceutically acceptable pro-drug thereof and administering to the subject a second amount of a TOP1 inhibitor. In some embodiments, the TOP1 inhibitor is irinotecan, topotecan, camptothecin, lamellarin D, and / or combinations thereof.

The present application belongs to the technical field of biomedical materials and nano drugs, and discloses a polypeptide nano drug capable of inducing necrosis and autophagy related synergistic apoptosis and a preparation method and application thereof. X-DDP1 and DDP1 are self-assembled to form a responsive polypeptide nano drug, which provides a delivery platform for broad-spectrum chemotherapy drugs such as buforin RBG, irinotecan CPT11 or camptothecin CPT, realizes a Caspase-3 / GSH double-response mechanism, improves drug release specificity and spatial controllability, can promote RIPK3 aggregation and activate necrotic apoptosis in cells, can effectively inhibit the growth of cancer, and has potential clinical application value.

The invention discloses an analysis method for improving the intestinal toxicity action mechanism of irinotecan by using a traditional Chinese medicine compound, and particularly discloses an analysis method for improving the intestinal toxicity action mechanism of irinotecan by using Xiaochaihu decoction. Respectively administering different doses of common goldenrop decoction and a positive drug loperamide for treatment, and observing the perianal state, weight, food intake and water intake change of the rat; the method comprises the following steps: acquiring metabolic map information of colon contents of rats in each group, processing and analyzing data, screening out main differential biomarkers, and analyzing metabolic pathways involved in the main differential biomarkers; based on the main effective components of the Xiaochaihu decoction, the potential target spot and mechanism are further predicted, and the potential action mechanism is determined in combination with the metabolic pathway; finally, molecular biology is utilized to verify the mechanism, and a theoretical basis is provided for clinical traditional Chinese medicine for preventing and treating enterotoxicity of chemotherapeutic drugs.

The present invention relates to combination therapies for treating KRas G12D cancers. In particular, the present invention relates to methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of irinotecan (or an analog thereof) and a KRas G12D inhibitor, pharmaceutical compositions comprising a such compositions, kits comprising such compositions and methods of use thereof.

This invention discloses an alkaloid, its preparation method, and its application in the preparation of human carboxylesterase 2 inhibitors. The residue of Paeonia lactiflora after ultrasonic extraction was extracted with 95% ethanol and then with ethyl acetate to obtain ethyl acetate extract CS-5. Separation was performed by silica gel column chromatography, using a gradient elution with petroleum ether-acetone mixed solvent and dichloromethane-methanol mixed solvent to obtain six eluent fractions, named A-F. Compound D was separated by silica gel column chromatography, Sephadex LH-20 column chromatography, and semi-preparative HPLC to obtain compound I-2. Compound F was separated by Sephadex LH-20 column chromatography and semi-preparative HPLC to obtain compounds I-1 and I-3. Compound I-1 was separated by a chiral HPLC column to obtain enantiomers I-(+)-1 and I-(–)-1. The four alkaloids of this invention have a pH range of 13.65–14.16. m At concentrations of M, it can significantly inhibit the activity of human carboxylesterase 2. Therefore, it can be applied to the preparation of attenuated and protective agents for anticancer drugs such as irinotecan.

This invention belongs to the field of nanoprodrug technology, specifically relating to an NQO1-activated prodrug, its preparation method, and its applications. The prodrug molecule of this invention can self-assemble into a stable nanodrug in an aqueous phase without the use of excipients. This nanodrug exhibits good structural stability, possesses both active and passive targeting capabilities, and achieves specific recognition of tumor cells, resulting in precise chemotherapy, improved treatment efficiency, and reduced toxic side effects on normal cells. Furthermore, the release of irinotecan can be monitored in real time using changes in its fluorescence. The preparation method is simple and holds promise for widespread application in the specific treatment of cancers with NQO1 overexpression.

Disclosed herein is use of a combination of Compound (A), or a pharmaceutically acceptable salt thereof, (also known as azenosertib or ZN-c3) and Compound (B), or a pharmaceutically acceptable salt thereof, or an antibody -drag conjugate comprising Compound (B), or a pharmaceutically acceptable salt thereof, for treating a disease, such as a cancer, wherein Compound (B) can be a topoisomerase I inhibitor (e.g., topotecan, belotecan, irinotecan, SN-38, govitecan, exatecan or deruxtecan).

The invention belongs to the technical field of medicinal chemistry, and discloses a human carboxylesterase 2A (hCES2A) self-activated covalent inhibitor as well as a preparation method and application thereof. The inhibitor is a novel benzamide-O-carbamate derivative (I) with a structure as shown in a formula (I) and pharmaceutically acceptable salts thereof, and the compound can powerfully and highly selectively inactivate the activity of human intestinal tract hCES2A. Further, the oral bioavailability of the oral prodrug is improved or the intestinal toxicity caused by the carboxylesterase 2A activated prodrug (such as irinotecan) is relieved. The IC50 value of the compound for inhibiting human carboxylesterase 2A can reach a nanomole level and is dose-dependent and time-dependent. The compound provided by the invention also has good safety, and has the advantages of simple preparation process, high yield and the like, which indicates that the compound has good application prospects.

Disclosed are methods, compositions, and kits for treating pediatric cancers using hydroxyureamethyl acylfulvene (LP-184) or pharmaceutically acceptable salts / solvates thereof. The methods include monotherapy and combination regimens for pediatric sarcoma, medulloblastoma, glioma (including DIPG), hepatoblastoma, Wilms tumor, and related malignancies. Combination therapies include LP-184 with vincristine, topoisomerase I poisons (topotecan or irinotecan), PARP inhibitors (e.g., rucaparib), or spironolactone, yielding additive or greater-than-additive reductions in tumor growth or cell viability.