88 results about "Integrelin" patented technology

The invention relates to conjugates of anti-integrin specific antibodies with cytotoxic compounds, the synthesis, selection, and use of such conjugates for use in cancer therapy or other diseases mediated by cell proliferation, cell migration, or inflammation and which pathology involves angiogenesis or neovascularization of new tissue. In addition the invention relates to combination therapy of such diseases wherein the treatment comprises use of said conjugates in combination with one or more other treatment modalities including but not limited to: chemotherapy, surgery or radiation therapy. The preferred conjugates contain maytansinoid compounds linked to the antibody by a disulfide linkage, and preferred chemotherapeutic agents are doxorubicin, a taxane, a camptothecin, a podophyllotoxin, a nucleoside analog, or a pyrimidine analog.

Specified phenylalanine derivatives and analogues thereof have an antagonistic activity to α 4 integrin. They are used as therapeutic agents for various diseases concerning α 4 integrin.

Specified phenylpropionic acid derivatives and analogues thereof have an antagonistic activity to α 4 integrin. They are used as therapeutic agents or preventive agents for various diseases concerning α 4 integrin, such as inflammatory diseases in which α 4 integrin-depending adhesion process participates in the pathology, rheumatoid arthritis, inflammatory bowel diseases, systemic lupus erythematosus, multiple sclerosis, Sjögren's syndrome, asthma, psoriasis, allergy, diabetes, cardiovascular diseases, arterial sclerosis, restenosis, tumor proliferation, tumor metastasis and transplantation rejection.

The invention relates to anti-α2 integrin antibodies and their uses. Humanized antibodies are disclosed that bind to the I domain of α2 integrin and inhibit the interaction of α2β1 integrin with collagen. Also disclosed are therapeutic uses of anti-α2 integrin antibodies in treating α2β1-mediated disorders, including anti-α2 integrin antibodies that bind to α2 integrin without activating platelets.

The invention relates to a high-performance angiogenesis inhibitor and a production method, which belongs to the field of the biological engineering pharmaceutical technology or protein polypeptide drugs. The invention designs a high-performance angiogenesis inhibitor RGD-ED with integrin compatibility, the inhibitor contains angiogenesis inhibition polypeptide isoleucine-valine-arginine-arginine-alanine-aspartate-arginine-alanine-alanine-valine-proline, and one or two ends of the inhibitor are respectively connected with polypeptides containing arginine-glycin-aspartate sequence. The RGD-ED of the invention can be synthesized. By the method of genetic engineering, the invention also expresses one of RGD-Eds in escherichia coli or other eukaryotic cells, and the RGD-ED is obtained by carrying out the separation, dissolution and renaturation of inclusion body protein and separation and purification by ion exchange chromatography. All the polypeptide sequences of the invention are modified by Polyethylene Glycol (PEG), heparin, dextran, polyvinylpyrrolidone (PVP), polyglycol-poly (amino acid) copolymer, palmitic acid, colominic acid and liposome, which includes liposome (REV), drying liposomal (DRV) and multivesicular liposome (Mvl). In vivo and in vitro experiments, the synthetic polypeptide sequence, product of genetic engineering and modified product of the invention can notably increase the effects of inhibiting the growth of endothelial cells, inhibiting angiogenesis and resisting tumor of the present angiogenesis inhibitors, and moreover, the high-performance angiogenesis inhibitor can be used as a drug curing solid tumors and rheumatoid arthritis.

The present invention provides methods that enable the user to identify inhibitors of tissue granulation in and around a wound site, thereby limiting excessive scar formation as the wounded tissue heals. The some granulation inhibitors identified using the methods of the invention inhibit granulation in and around a wound site up to five fold, with a corresponding decrease in the formation of scar tissue when tested on retinal injuries. Granulation inhibitors that can be identified using the methods of the present invention include antibodies, peptides, nucleic acids (aptamers), and non-peptide small molecules.

Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against αIIbβ3 integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to αIIbβ3 integrin or to both αIIbβ3 and αVβ3 integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for αIIbβ3 integrin.

The present invention provides novel solid pharmaceutical dosage forms for oral administration comprising a therapeutically active amount of roflumilast, or a pharmaceutically acceptable salt thereof, a therapeutically effective amount of N-(2-chloro-6-methylbenzoyl)-4-[(2,6-dichlorobenzoyl)amino]-L-phenylalanine-2-(diethylamino)ethyl ester, or a pharmaceutically acceptable thereof, and one or more pharmaceutically acceptable excipients. These novel solid pharmaceutical dosage forms are useful in the treatment or control of asthma. The present invention also provides a method for treating asthma employing the solid pharmaceutical dosage forms and a method for preparing the pharmaceutical dosage forms.

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

The invention discloses fusion protein with anti-tumor, anti-inflammation and oculopathy-treatment functions and a preparation method and application thereof, which belong to the technical field of biological pharmacy. Specifically, the invention relates to the fusion protein of an integrin blocking agent, which has the function of inhibiting tumor angiogenesis and has the integrin affinity and the combining capacity. A rigid (R) or flexible (F) linker is adopted to fuse two polypeptides, so as to respectively obtain protein A and protein G, the medicine effect can be increased, the half-life period can be extended, the stability can be enhanced, and the fusion protein has the characteristics of strong action effect, low toxicity and the like and can be used for preventing and treating solid tumors, all kinds of inflammation and angiogenesis oculopathy. The fusion protein structurally comprises two angiogenesis inhibiting polypeptides and the amino acid linker between the two angiogenesis inhibiting polypeptides, and the fusion protein is expressed in colibacillus or eukaryocyte by using a genetic engineering method and is obtained through separation and purification of a GST (Glutathione S Transferase) affinity column.

The invention discloses an integrin blocker polypeptide as well as a preparation method and application thereof, and belongs to the field of biopharmacy. The integrin blocker polypeptide only has 9 to 17 amino acids from the polypeptide I to the polypeptide X, and is synthesized by using a solid-phase synthesis method, so that the integrin blocker polypeptide also has an in-vivo immune protection function and can be used for treating arthritis even the number of the amino acids in the integrin blocker polypeptide is reduced. The integrin blocker polypeptide has the function of inhibiting neovascularization and has the activity of inhibiting endothelial cell migration so as to prevent and treat diseases relevant to blood vessels and inflammations comprising oculopathy relevant to neovascularization. The integrin blocker polypeptide has the high anti-tumor activity to various types of tumors, so that the cost is greatly lowered. The integrin blocker polypeptide has the good function for treating chronic infectious arthritis, so that the adaptability and the applicable diseases of the integrin blocker polypeptide are increased. Thus, the social and economic values of the integrin blocker polypeptide are enlarged.

The invention relates to anti-α2 integrin antibodies and their uses. Humanized antibodies are disclosed that bind to the I domain of α2 integrin and inhibit the interaction of α2β1 integrin with collagen. Also disclosed are therapeutic uses of anti-α2 integrin antibodies in treating α2β1-mediated disorders, including anti-α2 integrin antibodies that bind to α2 integrin without activating platelets.

Phenylalanine derivatives of the following formula, analogues thereof and pharmaceutically acceptable salts thereof have an antagonistic activity to α4 integrin. They are used as therapeutic agents or preventive agents for various diseases concerning α4 integrin in which α4 integrin-depending adhesion process participates in the pathology, such as inflammatory diseases, rheumatoid arthritis, inflammatory bowel diseases, systemic lupus erythematosus, multiple sclerosis, Sjögren's syndrome, asthma, psoriasis, allergy, diabetes, cardiovascular diseases, arterial sclerosis, restenosis, tumor proliferation, tumor metastasis and transplantation rejection.wherein R1 is a methyl group and R2 is a methoxy group.

The invention discloses application of HM-3 and platinum, paclitaxel or capecitabine medicine for preparing a solid tumor medicine, belonging to the field of medicines for treating tumor. Platinum, paclitaxel or capecitabine antimetabolites serve as active components and accompanied by a pharmaceutically acceptable carrier to be prepared into various pharmaceutically acceptable preparations. A plurality of experiments show that an integrin blocker HM-3 is clear in target; the integrin blocker HM-3 is reasonably used together with the platinum, paclitaxel or capecitabine for effectively suppressing growth of tumors in lung cancer, liver cancer, stomach cancer, breast cancer, cervical cancer, ovarian cancer, intestinal cancer, and the like. The combined medicine serves as a medicine and is capable of effectively treating tumors; the combined medicine is scientific, reasonable, feasible and effective, so that the treatment spectrum for treating the tumors is greatly expanded; the toxic and side effects are reduced; the HM-3 and platinum, paclitaxel or capecitabine medicine is prominent in social value and market value.

The present invention relates to methods and compositions designed for the treatment, management or prevention of cancer. The methods of the invention comprise the administration of an effective amount of one or more antagonists of Integrin αVβ3 alone or in combination with the administration of an effective amount of one or more other agents useful for cancer therapy. The invention also provides pharmaceutical compositions comprising one or more antagonists of Integrin αVβ3 and / or one or more other agents useful for cancer therapy. In particular, the invention is directed to methods of treatment and prevention of cancer by the administration of a therapeutically or prophylactically effective amount of one or more antagonists of Integrin αVβ3 alone or in combination with standard and experimental therapies for treatment or prevention of cancer. Also included are methods for screening for epitope-specific Integrin αVβ3 antagonists which can be used according to the methods of the invention. In addition, methods for facilitating the use of Integrin αVβ3 antagonists in the analysis of Integrin αVβ3 expression in biopsies of animal model and clinical study samples are also contemplated.

The invention relates to compounds of formula (A):or a salt thereof, wherein R1, R2, R5a, R5b, R6a, R6b, R7a, R7b, R8a, R8b, R9a, R9b, R10a, R10b, R11a, R11b, R21, n, and G are as described herein. Compounds of formula (I) and pharmaceutical compositions thereof are αVβ6 integrin inhibitors that are useful for treating fibrosis such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP).

Provided herein are compositions, methods and kits for treating inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis in a mammal in need thereof. The method include administering to a subject with IBD a combination therapy containing a therapeutically effective amount of a chemokine receptor 9 (CCR9) inhibitor compound and a therapeutically effective amount of an anti-α4β7 integrin antibody such as vedolizumab. Also provided herein is a kit containing the CCR9 inhibitor compound and anti-α4β7 integrin antibody.

Compounds of the formulaare useful in the treatment of various disorders including, but not limited to, cancer (tumor metathesis, tumorgenesis / tumor growth), angiogenesis (as in cancer, diabetic retinopathy, rheumatoid arthritis), restenosis (following balloon angioplasty or stent implantation), inflammation (as in rheumatoid arthritis, psoriasis), bone diseases (osteopenia induced by bone metastases, immobilization and glucocortocoid treatment, periodontal disease, hyperparathyroidism and rheumatoid arthritis), and as antiviral agents. Novel method of making compounds of formula I are also provided.

The invention discloses a preparation method of targeting composite nanoparticle. The invention uses phospholipids, pegylated phospholipids and polyethylene glycol-distearoyl phosphatidyl ethanolamine connected with RGD (arginine-glycine-aspartic acid) as an emulsifier, and uses a binary mixture solvent system of dichloromethane and ethanol to prepare the targeting composite nanoparticle which contains PLGA (poly lactic-co-glycolic acid) as the nucleus and contains the phospholipids and pegylated phospholipids as a shell by one-step emulsification method. The invention uses the hydroxyl camptothecin as a model drug to prepare the RGD targeting phospholipid-polymer composite nanoparticle with high drug loading rate (18.9%) and high entrapment efficiency (94.5%). The phospholipid monolayer and polyethylene glycol hydration layer located on the surface of the targeting composite nanoparticle prepared by the method provided by the invention can significantly reduce protein adsorption and extend the action time in vivo; the RGD connected with the shell of the composite nanoparticle can effectively promote nanoparticles specific binding to tumor cells or tumor new vessels with high expression of integrin, and improve the local drug concentration, so as to enable the targeting composite nanoparticles to have a better anti-tumor effect.

The invention relates to conjugates of anti-integrin specific antibodies with cytotoxic compounds, the synthesis, selection, and use of such conjugates for use in cancer therapy or other diseases mediated by cell proliferation, cell migration, or inflammation and which pathology involves angiogenesis or neovascularization of new tissue. In addition the invention relates to combination therapy of such diseases wherein the treatment comprises use of said conjugates in combination with one or more other treatment modalities including but not limited to: chemotherapy, surgery or radiation therapy. The preferred conjugates contain maytansinoid compounds linked to the antibody by a disulfide linkage, and preferred chemotherapeutic agents are doxorubicin, a taxane, a camptothecin, a podophyllotoxin, a nucleoside analog, or a pyrimidine analog.

The invention discloses 1,3-dihydro-1-oxo-2H-isobenzazole compounds (I) and pharmaceutically acceptable salts thereof, and also discloses preparation methods for the compounds, and uses of the compounds in preparing medicines for preventing and / or treating various diseases caused by the mediation of integrin alpha v beta 3, such as tumor metastasis, tumor growth, solid tumor growth, angiogenesis, retinopathy, macular degeneration, osteoporosis, arthritis, smooth muscle cell migration and atherosclerosis symptoms or diseases.

The present invention provides methods for predicting whether an individual having inflammatory bowel disease (IBD) is likely to respond to vedolizumab treatment. Also provided are methods for predicting whether an individual with IBD such as Crohn's disease or ulcerative colitis will develop autoantibodies against vedolizumab. The present invention also provides a treatment regimen for an IBD patient which includes measuring the level of one or more predictive markers of response to vedolizumab prior to administering the anti-α4β7 integrin drug.

The invention discloses a traditional Chinese medicine composition for treating luteal phase defect type infertility and menstrual disorder. The traditional Chinese medicine composition disclosed by the invention is prepared from the following components in parts by weight: 1-6 parts of fried radix paeoniae alba, 1-9 parts of common yam rhizome, 1-6 parts of dogwood, 0.5-3 parts of vinegar baked bupleurum root, 1-9 parts of the seed of Chinese dodder, 1.5-9 parts of sliced cornu cervi, 1.5-9 parts of amethyst and 1-6 parts of radix salviae miltiorrhizae. According to the compound composition provided by the invention, by means of syndrome differentiation and treatment, the formula is obtained through a lot of experimental screening under the guidance of theories of traditional Chinese medicines; experimental results show that the traditional Chinese medicine composition is capable of improving the structure and form of ovary mitochondria endoplasmic reticulum, improving structures of endometrial glands and mesenchyme, adjusting ovary secreted active substances E2 and P, reducing endometrium estrogen receptors and progestrone receptors and increasing expression of integrins alpha v and beta 3; therefore, the endometrium receptivity can be increased; the embryo implantation action is promoted; the traditional Chinese medicine composition has the good effect for treating infertility; and furthermore, the traditional Chinese medicine composition is free from toxic and side effect, and safe and reliable to use.

The present invention relates to novel tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidine compounds that are antagonists of alpha V (alphav) integrins, for example alphavbeta3 and alphavbeta5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by alphavbeta3 and alphavbeta5 integrins, including conditions such as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula: where R1, R2, R3, R4, R5, R6, R7R8, R9, R10, m and n are defined herein.

The present invention relates to sulphonamide derivatives, whith a urea moiety. The invention also relates to the use of the derivatives as inhibitors of collagen receptor integrins, especially α2β1 integrin inhibitors e.g. in connection with diseases and medical conditions that involve the action of cells and platelets expressing collagen receptors, their use as a medicament, e.g. for the treatment of thrombosis, inflammation, cancer and vascular diseases, pharmaceutical compositions containing them and a process for preparing them. The sulphonamide derivatives have the general formula (I) or (I′).

The invention discloses 18F-E[c(RGDyk)2], a medicine box used for automatic production thereof, and a preparation method and use of the medicine box, relates to a polyethylene terephthalate (PET) developer and a preparation method and use thereof and relates to the technical field of radiative medicines and nuclear medicines. The medicine box contains a raw material reagent A and a raw material reagent B. A bottle A contains E[c(RGDyk)2]-NO2; and A bottle B contains acetonitrile solution of crown ether K222 / K2CO3. The 18F-E[c(RGDyk)2] prepared by the medicine box has high absorbing performance and excellent retaining performance in model mouse tumor, and has a very high target / non target ratio, excellent pharmacokinetic characteristic and high biological performance, and can completely meet the requirements of PET developer of tumour integrin alphavbeta3 receptor.

The invention relates to compounds of Formula (I):wherein R1, R2 and R3 are as defined in the description and claims, or pharmaceutically acceptable salts thereof, having αvβ6 integrin antagonist activity. The invention also relates to pharmaceutical compositions including a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and to the use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof in therapy, including in the treatment of a disease or condition for which an αvβ6 integrin antagonist is indicated, in particular the treatment of idiopathic pulmonary fibrosis.

The invention relates to compounds of formula (A):or a salt thereof, wherein R1, R2, R5a, R5b, R6a, R6b, R7a, R7b, R8a, R8b, R9a, R9b, R10a, R10b, R11a, R11b, R21, n, and G are as described herein. Compounds of formula (I) and pharmaceutical compositions thereof are αvβ6 integrin inhibitors that are useful for treating fibrosis such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP).