725 results about "Camptothecin" patented technology

The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.

Disclosed herein are compositions and methods of use comprising combinations of anti-CD22 antibodies with a therapeutic agent. The therapeutic agent may be attached to the anti-CD22 antibody or may be separately administered, either before, simultaneously with or after the anti-CD22 antibody. In preferred embodiments, the therapeutic agent is an antibody or fragment thereof that binds to an antigen different from CD22, such as CD19, CD20, CD21, CD22, CD23, CD37, CD40, CD40L, CD52, CD80 and HLA-DR. However, the therapeutic agent may an immunomodulator, a cytokine, a toxin or other therapeutic agent known in the art. More preferably, the anti-CD22 antibody is part of a DNL complex, such as a hexavalent DNL complex. Most preferably, combination therapy with the anti-CD22 antibody or fragment and the therapeutic agent is more effective than the antibody alone, the therapeutic agent alone, or the combination of anti-CD22 antibody and therapeutic agent that are not conjugated to each other. Administration of the anti-CD22 antibody and therapeutic agent induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease.

Oral formulations of pharmaceuticals are provided with enhanced bioavailability by targeting specific regions of the gastrointestinal tract. Particularly, water soluble and acid-labile drugs such as cytidine analogs (e.g., decitabine) and 2'-deoxyadenosine analogs (e.g., pentostatin) are formulated with pH-sensitive polymers so that these drugs are preferably absorbed in the upper regions of the small intestine, such as the jejunum. In addition, drugs with poor oral bioavailability such as camptothecin compounds (e.g., 9-nitro-camptothecin) can also be formulated using similar strategies in order to significantly improve their oral bioavailability. These formulations can be used to treat a wide variety of diseases or conditions, such hematological disorders, benign tumors, cancer, restenosis, inflammatory diseases, and autoimmune diseases.

The disclosure includes hydroxamic compounds of Formula I: (Formula I) wherein Z, L, R₁, R₂, and R₃ are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compounds.

A method and devices for localized delivery of a chemotherapeutic agent to solid tumors, wherein the agent does not cross the blood-brain barrier and is characterized by poor bioavailability and/or short half-lives in vivo, are described. The devices consist of reservoirs which release drug over an extended time period while at the same time preserving the bioactivity and bioavailability of the agent. In the most preferred embodiment, the device consists of biodegradable polymeric matrixes, although reservoirs can also be formulated from non-biodegradable polymers or reservoirs connected to implanted infusion pumps. The devices are implanted within or immediately adjacent the tumors to be treated or the site where they have been surgically removed. The examples demonstrate the efficacy of paclitaxel and camptothecin delivered in polymeric implants prepared by compression molding of biodegradable and non-biodegradable polymers, respectively. The results are highly statistically significant.

It is intended to provide water-soluble derivative of camptothecins which are excellent in therapeutic effect and suitable for chemotherapy for cancer. Namely, a water-soluble high-molecular weight derivative of camptothencins being excellent in sustained-release which is obtained by ester-bonding a carboxylic acid group of a polyethylene glycol-polycarboxylic acid polymer to a phenolic hydroxyl group of phenolic camptothencins.

The present invention relates to a novel compound of use in the improved delivery of therapeutic drug agents into target cells or tissues, composition comprising the same and uses thereof. The compound is more specifically a conjugate of a peptide moiety and a camptothecin, a derivative or analog thereof which provides numerous benefits, including enhancement in terms of aqueous solubility, pharmacokinetics and tissue distribution, enlargement of the therapeutic index, and limitation of the inter-patient metabolic variability, as well as improvement of delivery of the biologically active ingredient to the target cells or tissues.

Compositions which comprise a liposomal water-soluble camptothecin and optionally a liposomal fluoropyrimidine in combination with a vascular epithelial growth factor (VEGF) inhibitor such as cetuximab or an epidermal growth factor receptor (EGFR) inhibitor such as bevacizumab are useful in achieving enhanced therapeutic effects for the treatment of cancer.

The present invention relates to a conjugate of hydrophilic polymer-multicarboxyl oligopeptide and drug molecule of the following formula:

wherein: P is a water soluble polymer; m is an integer of 2˜12; j is an integer of 1˜6; R_i is a group selected from H, C_1-12 alkyl, substituted aryl, aralkyl, heteroalkyl and substituted alkyl; X and Z are linking groups; and TA is drug molecule. The conjugate has low toxicity and an ability to carry more than one drug molecule to improve solubility, sustain and control drug release, and has a remarkably enhancing effect especially to antitumor drug such as paclitaxel and camptothecin etc.

The invention discloses a graphene/hyaluronic acid assembly taking cyclodextrin as a medium. The graphene/hyaluronic acid assembly is a nano supermolecule assembly synthesized based on beta-cyclodextrin-modified graphene and adamantine-modified hyaluronic acid, wherein graphene is modified by beta-cyclodextrin; by virtue of strong host-guest interaction between beta-cyclodextrin and adamantine, graphene and hyaluronic acid are combined together to form the supermolecule assembly. The graphene/hyaluronic acid assembly has the advantages that the supermolecule assembly greatly improves stability and biocompatibility of the cyclodextrin-modified graphene under physiological conditions; by utilizing targeted recognition action of hyaluronic acid on tumor cells, the supermolecule assembly can selectively kill the cancer cells, and has anti-cancer activity higher than that of pure drug camptothecin; the targeted drug transmission system is simple in preparation process, easy to implement and low in material cost, and has potential application prospect in clinic treatment of cancers.

The invention relates to a method for preparing a graphene oxide double-targeting medicine carrier material, and a medicine loaded by the carrier material. The method is used for preparing the carrier material and the loaded medicine. The invention solves the problems that the conventional nano-medicine carrier has a complicated structure, is high in synthetic cost and low in efficiency, and cannot be massively prepared easily. The method for preparing the graphene oxide double-targeting medicine carrier material comprises the following steps of: preparing carboxymethylated graphene oxide; preparing a graphene oxide-biologically targeting molecule composite; and preparing the graphene oxide double-targeting medicine carrier material, wherein the loaded medicine is one or more of doxorubicin hydrochloride, paclitaxel, hydroxycamptothecine and daunomycin.

The invention discloses camptothecin drugs and antibody conjugates thereof. The inventor designs a series of anti-tumor exatecan active derivatives on the basis of comprehensive understanding of ADC drugs, and experiments prove that newly designed anti-tumor molecular compounds show good anti-tumor activity in the experiments.

The invention is directed to an improved drug delivery system that includes a micelle, comprising polyethylene glycol and a lipid component, and a pharmaceutical agent dispersed in the lipid component. The delivery system may also include a targeting ligand. The micelle delivery system of the invention is capable of stabilizing, inter alia, poorly soluble pharmaceutical agents and increasing their delivery efficacy. Appropriate pharmaceutical agents useful in the system of the invention include anti-inflammatory agents, agents for photodynamic therapy, anti-tumor agents, anti-neoplastic agents, anti-metastatic agents, and imaging agents, as well as hydrophobized derivatives thereof. Specifically, the pharmaceutical agent can be porphyrin, chlorine-6-trimethyl ester, tamoxifen, paclitaxel, 1,3-bis(2-chloroethyl)-1-nitrosourea, camptothecin, ellipticine, rhodamine, dequalinium, diphenylhexatriene, vitamin K3, diethylene triamine pentaacetic acid, or a functional derivative thereof. The micelles in the system of the invention have low critical micellar concentration and high kinetic stability, which provides great advantages in biodistribution, for example, accumulation at the site of a tumor.

A stable liposome composition comprises camptothecin or derivatives thereof, phospholipid, cholesterol, organic acids and the buffer salts of the camptothecins, and pharmaceutically-acceptable excipient. The composition can specifically increase the stability of the camptothecins, improve the curative effect, and reduce the toxic and side effects of the camptothecins.

Medical implants are provided which release an anthracycline, fluoropyrimidine, folic acid antagonist, podophylotoxin, camptothecin, hydroxyurea, and/or platinum complex, thereby inhibiting or reducing the incidence of infection associated with the implant.

The invention belongs to the field of pharmaceutical preparations, and relates to preparation of a novel target nano carrier and application of the novel target nano carrier in a camptothecin drug targeting delivery system. The system can be represented as PAMAM-HA/drug, wherein PAMAM is polyamide amine-amine arboraceous macromolecules of different generations, HA is hyaluronic acid of different molecular weights, and the drug is one or more of camptothecin anticancer drugs such as camptothecin, 10- hydroxycamptothecine, topotecan and the like. The carrier is used for wrapping the camptothecin drugs, and has the actions of prolonging the drug blood circulation time, improving the drug bioavailability, reducing the non-tumor part concentration of the drug, reducing the drug cytotoxicity, and simultaneously protecting the lactonic rings of the camptothecin drugs from damage, thereby improving the tumor treatment efficiency from multiple aspects. The nano carrier provided by the invention has important significance in promoting the safe delivery of the camptothecin drugs and the effective treatment of tumor.

The invention provides camptothecin-adriamycin prodrug. A structural formula of the prodrug is shown as a formula (I), wherein R1 is camptothecin or derivative group thereof, R2 is one of -CH2- or -O-, R3 is one of -CH2- or -O-, X is one of S or -CH2-, and n1 and n2 are numbers of repeated units, and are integers from 0 to 10. The prodrug can be easily wrapped by amphiphilic polymer to form nanoparticles. The nanoparticles are high in drug carrying efficiency and drug carrying capacity and capable of quickly releasing unmodified camptothecin and adriamycin in the presence of glutathione, and the nanoparticles can be effectively taken in by tumor cells to kill the same. The invention further provides a preparation method of the prodrug, a preparation of the prodrug and application of the prodrug in preparing cancer treating drug.

The invention discloses a 7-ethyl-10-hydroxycamptothecin amphiphilic polymer prodrug comprising a segment of polyethylene glycols and a segment of poly(7-ethyl-10-hydroxycamptothecin); and the poly(7-ethyl-10-hydroxycamptothecin) is formed in the way that hydroxyls at the tenth position or/and twentieth position on 7-ethyl-10-hydroxycamptothecin are connected with a polymer framework through degradable chemical bonds. Polyethylene glycols with different lengths are introduced, so that the prodrug is self-assembled in water to form nano particles, and the solubility of the 7-ethyl-10-hydroxycamptothecin in water is greatly increased. The nanometer size of the polymer prodrug is adjustable so that the 7-ethyl-10-hydroxycamptothecin amphiphilic polymer prodrug can effectively meet the requirement for sizes under different tumor systems and target different intracorporeal organs, and cancers of different organs are possibly treated.