69 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 present invention provides an antibody-drug conjugate, a preparation method thereof, and an application thereof. The structural formula of the antibody-drug conjugate is as follows. Among them, mAb is the anti-HER2 antibody trastuzumab; the conjugate is obtained by Michael addition of the thiol group obtained by reducing the inter-chain disulfide bond of mAb with the linker-irinotecan conjugate LD038; n ranges from 1 to 10. The binding activity and internalization activity of the antibody-drug conjugate to various tumor target cells are not affected; compared with the same type of antibody-drug conjugate, the antibody-drug conjugate PRO1102 synthesized by the preparation method of the antibody-drug conjugate of the present invention shows certain advantages in terms of in vitro cytotoxicity to tumor cells, anti-tumor activity in rats in vivo, and in vivo pharmacokinetics.

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 to a pharmaceutical composition comprising a combination of anticancer agents, capable of creating a synergistic effect when co-administer in the treatment of cancer, and more specifically, the present invention suggests anticancer agenst capable of creating a synergistic effect when co-administered with gossypol and phenformin. The anticancer agents selected as said anticancer agents in the present disclosure are sorafenib, vemurafenib, irinotecan, cisplatin, paclitaxel, and doxorubicin, and each of the aforementioned anticancer agent, when co-administered as a triple-drug combination with gossypol and phenformin can provide a significant synergistic effect in terms of the effect of suppressing the proliferation of cancer and killing cancer cell, compared to each mono-drug treatment group and a dual-drug treatment group of gossypol+phenformin.

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.

The invention relates to preparation of a novel indole camptothecin derivative and an application of the novel indole camptothecin derivative in an anti-tumor aspect. The structural general formula of the compound is shown in the specification. In-vitro cytotoxic activity screening results show that the novel indole camptothecin derivative has broad-spectrum antitumor activity, and shows relatively strong inhibitory activity on human liver cancer cells (HepG2), human non-small cell lung cancer cells (A549), human colon cancer cells (SW480), human intrahepatic bile duct cancer cells (RBE), human breast cancer cells (MCF-7), human pancreatic cancer cells (BxPC3), human bladder cancer cells (T24) and human bladder cancer cells (umuc3). Wherein the anti-tumor activity of the compound D-18 is the most prominent, the compound D-18 shows a relatively strong inhibition effect on the tested 8 tumor cell lines, the IC50 range is 0.2585-10.69 mu M, the compound D-18 is obviously superior to that of a contrast drug irinotecan, and the activity of the compound D-18 is equivalent to that of topotecan. Therefore, the indole camptothecin derivative is expected to be developed into a novel antitumor drug. # imgabs0 #

To provide a pharmaceutical composition for cancer treatment which shows a synergistic cancer therapeutic effect when used in combination with an anti-tumor agent, and can be easily used as a cancer therapeutic agent and a combination therapeutic pharmaceutical.SOLUTION: Provided is a cancer treatment application of nanoparticles containing a slightly soluble camptothecin-based compound and a combined administration therapy with an anti-tumor agent using the application. In one embodiment, a combination pharmaceutical preparation for pancreatic cancer treatment contains: particles including SN-38(7-ethyl-10-hydroxycamptothecin), irinotecan, and an amphiphilic block copolymer made of a hydrophobic block and a hydrophilic block; and one or more kinds of anti-tumor agents selected from the group consisting of nab-paclitaxel as an active ingredient, the amphiphilic block copolymer being constituted of A-B or A-B-A block, (a) A is a hydrophilic polymer and is monomethoxypolyethylene, and (b) B is a hydrophobic polymer and is poly-D,L-lactide or a derivative thereof.SELECTED DRAWING: Figure 2

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.

The present invention discloses a selenium-rich probiotic that affects irinotecan-induced diarrhea and intestinal flora in mice, establishes an irinotecan-induced diarrhea mouse model, and administers selenium-rich probiotics by long-term oral gavage to evaluate its effects on irinotecan-induced diarrhea and intestinal flora in mice. The mice in the experimental group were given selenium-rich probiotics by oral gavage every day, and the weight, diarrhea grade, immune index, intestinal flora and ileum tissue structure of the mice were measured. The results show that selenium-rich probiotics can inhibit weight loss and reduced immune function caused by irinotecan; reduce the incidence of diarrhea and the average diarrhea grade in mice, and alleviate irinotecan-induced diarrhea in mice; reduce the content of Clostridium, Escherichia coli and Bacteroidetes associated with β-D-glucuronidase, and increase the content of bifidobacteria in the intestine; alleviate the damage of intestinal mucosa, cells and glands of mice caused by irinotecan.

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 provides a preparation method of folic acid modified SN38 derivative lipidosome and application of the folic acid modified SN38 derivative lipidosome in tumor treatment. A blank folic acid liposome containing glutathione (GSH) is prepared through a film ultrasonic method, and an SN38 derivative solution and the blank folic acid liposome are mixed and incubated to obtain the SN38 derivative folic acid liposome. The SN38 folic acid lipidosome prepared by the invention is of a spherical vesicle structure, and is regular in form and free of rupture; the average particle size is 118 nm, and the Zeta potential is-25 mV; and good stability and obvious slow release performance are realized. The SN38 folic acid lipid disclosed by the invention shows enhanced cytotoxicity and cellular uptake, which proves that the SN38 folic acid lipid has enhanced tumor targeting ability. Both the SN38 folic acid liposome and the SN38-Atba folic acid liposome disclosed by the invention can generate a remarkable growth inhibition effect on tumors, and the treatment effect of the SN38 folic acid liposome and the SN38-Atba folic acid liposome is obviously superior to that of the SN38 liposome and a first-line chemotherapeutic drug irinotecan clinically used for treating the tumors. Therefore, the invention provides a new treatment strategy for tumors, and has very important clinical significance and social significance.

The invention discloses application of polaprezinc in preparation of a medicine for relieving gastrointestinal toxicity caused by chemotherapy, and belongs to the technical field of medicine. Polaprezinc is provided for relieving gastrointestinal toxicity caused by irinotecan for the first time, can effectively improve mouse small intestine length shortening caused by irinotecan, meanwhile can reduce intestinal inflammation and relieve mouse ileum injury caused by irinotecan, effectively improves the intestinal barrier function of mice, and can be used for preparing medicines for preventing and treating irinotecan. According to the present invention, the compound has the significant alleviation effect on the intestinal toxicity caused by irinotecan, can be used for preparing the drug for alleviating the gastrointestinal toxicity caused by chemotherapy, and is expected to alleviate the chemotherapy-related gastrointestinal toxicity by combining the application of polaprezinc for intervention in the tumor chemotherapy process, such that the new drug choice is provided for the clinical alleviation of the chemotherapy-induced intestinal adverse reaction.

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.

Provided are methods and compositions for treating Alzheimer's disease (AD). Aspects of the present disclosure include methods of treating Alzheimer's disease (AD), the methods comprising administering to a subject having Alzheimer's disease a therapeutically effective amount of irinotecan and letrozole. Aspects of the present disclosure further include pharmaceutical compositions comprising irinotecan, letrozole, and a pharmaceutically acceptable carrier. Use of such compositions for treating Alzheimer's disease (AD) are also provided.

The present disclosure relates to a pharmaceutical composition comprising a combination of anticancer agents, capable of creating a synergistic effect when co-administer in the treatment of cancer, and more specifically, the present invention suggests anticancer agents capable of creating a synergistic effect when co-administered with gossypol and phenformin. The anticancer agents selected as said anticancer agents in the present disclosure are sorafenib, vemurafenib, irinotecan, cisplatin, paclitaxel, and doxorubicin, and each of the aforementioned anticancer agent, when co-administered as a triple-drug combination with gossypol and phenformin can provide a significant synergistic effect in terms of the effect of suppressing the proliferation of cancer and killing cancer cell, compared to each mono-drug treatment group and a dual-drug treatment group of gossypol+phenformin.

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.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to Trop-2 or CEACAM5 and the immunoconjugate may be administered at a dosage of between 4 mg / kg and 16 mg / kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg / kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the immunoconjugate is effective to treat cancers that are refractory to or relapsed from irinotecan.

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