36 results about "Somatostatin Analogue" patented technology

The invention provides peptide derivatives designed to deliver peptides having growth factor inhibitory activity, especially somatostatin analogs, to the retina by sequential metabolism. The peptide derivatives, which comprise a dihydropyridine<CUSTOM-CHARACTER FILE="US06440933-20020827-P00900.TIF" ALT="custom character" HE="20" WI="20" ID="CUSTOM-CHARACTER-00001" / >pyridinium salt-type redox targetor moiety, a bulky lipophilic function and an amino acid / dipeptide / tripeptide spacer, are used in the prevention and treatment of diabetic retinopathy.

Compounds having somatostatin activity of the following Formula I, wherein,R1 is aryl, substituted-aryl, and aryl-(lower-alkyl)-;R2 is lower alkyl, amino substituted lower alkyl, -carboxy-(lower-alkyl), -carbamic acid-(lower-alkyl) and -carboxy-(lower-alkyl)-aryl; andR3 and R4 are independently, lower-alkyl, aryl, substituted-aryl, (substituted-aryl)-(lower-alkyl)-, heteroaryl, (heteroaryl)-(lower-alkyl)-, substituted-heteroaryl, (substituted heteroaryl)-(lower-alkyl)-, heterocyclic, heterocyclic-(lower-alkyl)-, substituted-heterocyclic, (substituted-heterocylic)-(lower alkyl)-, -carboxy-(lower-alkyl), and -carboxy-(lower-alkyl)-aryl; or a pharmaceutically acceptable, ester, ether, or salt thereof; methods for their use; and preparation.

A subject afflicted with a cancer or precancerous condition is treated by administering an agent that increases expression of somatostatin receptors, and a cytotoxic recognition ligand. In an alternative embodiment, somatostatin analogs, which are radiolabeled are used to treat cancer or precancerous conditions.

Analogs of SRIF which are selective for SSTR4 in contrast to the other cloned SRIF receptors are useful in determining tissue and cellular expression of the receptor SSTR4 and its biological role in regulating tumor growth. SRIF analog peptides, such as des-AA1,2,4,5,12,13[Ala7]-SRIF; des-AA1,2,4,5,12,13[Aph7]-SRIF, des-AA1,2,4,5,12,13[Aph7]Cbm-SRIF; des-AA1,2,4,5,12,13[Tyr2,Ala7]-Cbm-SRIF, and des-AA1,2,4,5,12,13[Tyr7,CβMe-L-2Nal8]-SRIF, and counterparts incorporating D-Cys3 and / or D-Trp8 and / or Ala11, bind with high affinity to the cloned human receptor SSTR4 and activate the receptor, but they do not bind with significant affinity to human SSTR1, SSTR2, SSTR3 or SSTR5. By incorporating an iodinated tyrosine in position-2 in these SSTR4-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, cytotoxins or highly radioactive elements can be N-terminally coupled or complexed thereto.

A subject afflicted with a cancer or precancerous condition is treated by administering an agent that increases expression of somatostatin receptors, and a cytotoxic recognition ligand. In an alternative embodiment, somatostatin analogs, which are radiolabeled are used to treat cancer or precancerous conditions.

The invention provides a novel radionuclide labelled somatostatin analogue molecular probe and its application and belongs to the field of radiopharmaceuticals labelling and nuclear medicine technologies. A bifunctional chelator couples cyclic polypeptide Pasireotide, and then radionuclide is used for labelling so as to obtain a radionuclide labelled neuroendocrine neoplasm specific somatostatin analogue radioactive molecular probe. The molecular probe can be combined with a tumor expression somatostatin receptor (SSTR), and SSTR positive tumor tissue can be accurately positioned by means of nuclear medicine. Thus, the purpose of disease target molecular imaging diagnosis and treatment is achieved. The synthesized molecular probe has higher affinity and functional activity for SSTR and is expected to become a somatostatin analogue developer and tumor therapeutic agent with a good prospect.

The invention provides a conjugate of SSA (somatostatin analog), PEG (polyethylene glycol) and anticancer drugs and the preparation thereof. The macromolecule conjugate is made from the targeting group SSA, the hydrophilic long-chain PEG and the anticancer drugs by adopting linking arms through conjugating. The macromolecule conjugate has tumor-targeting property and long circulation function, can obviously improve the antitumor activity, reduces toxic side effect of the drugs, is more suitable for clinical application, and provides new ideas for research and development of the anticancer drugs.

The invention relates to a pharmaceutical composition, particularly to a pharmaceutical composition with antitumor activity. The pharmaceutical composition with antitumor activity comprises 5,6-dimethylxanthenone-4-acetic acid (DMXAA) or an pharmaceutically acceptable salt or ester thereof and one drug component selected from glycopeptide antibiotics, actinomycins, mitomycins, glucoside antibiotics, Colchicum alkaloid, elemenes, aromatic enzyme inhibitors, LH-RH receptor antagonists, animal antitumor drugs and somatostatin analogues. The synergic composition has better antitumor activity. More specifically, the invention provides an application of the composition in treating tumors.

The invention belongs to the field of medicines, and concretely relates to a 123 / 131I-labeled novel glycosylated somatostatin analogue 123 / 131I-Gluc-KE108 and a preparation method thereof. The preparation method of the 123 / 131I-labeled novel glycosylated somatostatin analogue 123 / 131I-Gluc-KE108 comprises the following steps: (S1) synthesizing a novel glycosylated somatostatin analogue Gluc-KE108;and (S2) labeling the Gluc-KE108 with 123 / 131I, wherein step (S1) comprises (S1-1) amino acid condensation, (S1-2) removal of Dde from a polypeptide, (S1-3) resection of the polypeptide from resin, (S1-4) cyclisation of the polypeptide, (S1-5) acidolysis of the polypeptide and purification of an intermediate, and (S1-6) glycosylation and purification of the polypeptide; and in step (S2), the Gluc-KE108 is labeled with the 123 / 131I through adopting an Iodogen technology or a chloramine-T technology.

The present invention features inter alia polypeptides comprising an Fc region comprising genetically-fused Fc moieties. In addition, the instant invention provides, e.g., methods for treating or preventing a disease or disorder in subject by administering the binding polypeptides of the invention to said subject.

The invention belongs to the field of pharmaceutics, and particularly relates to a novel Amphipathic compound with tumour target and long-circulation functions. The compound is formed by coupling three parts of a target radical somatostatin analogue, hydrophile long-chain polyethylene glocyl and lyophobic alkyl chain fatty acid or fatty amine. The invention relates to a preparation method of the compound. The invention also relates to a drug delivering system which has the tumour target and long-circulation functions and is applied to micelle, liposome, nanometer particles, nanometer suspensions and micro emulsion as the modifier. The invention has the characteristics that (1) the tumour target function of the modified carrier can be improved through the endocytosis deviated by the somatostatin receptor, and (2) the hydrophilic long chain can improve the hydrophilia on the surface of the modified carrier and has long-circulation characteristic in the body.

The invention provides an oral medication path of a somatostatin analogue polypeptide drug, and in particularly relates to an oral medication path of three somatostatin analogue polypeptides, including octreotide, vapreotide and lanreotide, belonging to the field of medicine. The invention provides the stability of the three somatostatin analogues in in-vitro artificial gastric juice and artificial intestinal juice, and the experiments prove that the three somatostatin analogue polypeptides are stable in the artificial gastric juice and can not be degraded; in the artificial intestinal juice, the three polypeptides are gradually degraded along with time, the sequences of the stabilities of the three polypeptides from high to low are as follows: octreotide, vapreotide and lanreotide. The invention further provides the absorbing states of the three polypeptides after the three polypeptides are given to a rat through intragastric administration, and describes the oral pharmacokinetic behaviors of the three polypeptides. According to the invention, on the basis of the original injection paths of the three polypeptides, the oral medication path of the three polypeptides is increased, so that the compliance of a patient is improved.

The present invention provides a combined drug for an injectable depot formulation having a superior effect of preventing and / or treating polycystic kidney disease. More specifically, the present invention relates to a drug for preventing and / or treating polycystic kidney disease, which is an injectable depot formulation comprising a particle containing tolvaptan or a prodrug thereof and a somatostatin analogue. The present invention also relates to a method for preventing and / or treating polycystic kidney disease using the drug.

A pharmaceutical formulation including a chelator-somatostatin receptor ligand and a transchelator is provided. The chelator-somatostatin receptor ligand is conjugated with a metal source or a radionuclide source, whereas the transchelator is capable of capturing free metal source or radionuclide source that is not conjugated to the chelator-somatostatin receptor ligand. By using such pharmaceutical formulation, the preparation of radiolabeled somatostatin analogues could be made more efficient, and is feasible for imaging of SSTR pathway-activated systems in cancers and neurological diseases.

The invention provides peptide derivatives designed to deliver peptides having growth factor inhibitory activity, especially somatostatin analogs, to the retina by sequential metabolism. The peptide derivatives, which comprise a dihydropyridine<custom-character file="US20030211981A1-20031113-P00900.TIF" wi="20" he="20" id="custom-character-00001" / >pyridinium salt-type redox targetor moiety, a bulky lipophilic function and an amino acid / dipeptide / tripeptide spacer, are used in the prevention and treatment of diabetic retinopathy.

The invention belongs to the field of biotechnology and microbe and animal cell lines and specifically relates to a humanized drug-resistant GH-type pituitary tumor cell strain huashanc-CH, especially to a first international humanized drug-resistant GH-type pituitary tumor cell strain huashanc-CH and its establishment method and application. Through isolated culture of pituitary tumor cells from a patient with clinical drug-resistant GH-type pituitary tumor, the humanized drug-resistant GH-type pituitary tumor cell strain huashanc-CH is obtained. The cell strain is passaged for 50 times for the first time and is mostly round or elliptical, cytoplasm is abundant, and nucleus is large and round. It shows through experimental results that the cell strain can be passaged stably, can secrete growth hormones continuously, is drug-resistant to somatostatin analogue, can be used to provide a necessary cell test tool for researches on pathogenic and drug-resistance mechanisms of pituitary tumor, research and development and screening of new drugs and new biotherapy and detection of related bio-engineering products and the like, and has exploring potential and application value.

The invention provides a somatostatin analogue and application thereof. The structure of the somatostatin analogue is as shown in formula I), a Phe-D-Trp-Lys-Thr motif with high affinity to a somatostatin receptor is reserved in the structure of the somatostatin analogue, the probe structure is modified through different chelating agents and different nuclides, and a broad-spectrum radiolabeled somatostatin molecular probe targeting a somatostatin receptor is designed. All subtypes of somatostatin receptors are targeted, and the probe is used as an early diagnosis probe for broad-spectrum neuroendocrine tumors. Therefore, precise medical treatment of early diagnosis, early discovery and early treatment of neuroendocrine tumors is realized.

The invention aims at providing a somatostatin analogue. An amino acid sequence of the somatostatin analogue is as follows: Hynic-D-Phe-cyclo[Cys-Tyr-D-Trp-Lys-Thr-Cys]-Thr-NH2; a molecular formula ofthe somatostatin analogue is C55H70N14O12S2. The invention further provides a preparation method of the somatostatin analogue or an analogue thereof; the somatostatin analogue or the analogue thereofis synthesized by adopting a 9-fluorenylmethoxycarbonyl solid-phase synthesis (FMOC-SPPS) method or an Fmoc-tBu solid-phase synthesis method. The 99mTc-labeled somatostatin analogue provided by the invention has the advantages of relatively high labeling rate of a product, high stability and capability of directly labeling; a cell experiment and a mouse experiment prove that a label can be used for directly reflecting a tumor position of each organ and the result is accurate.

Conjugates of carriers and hydrogels for controlling the biological half-life of somatostatin and its analogs are disclosed.

Conjugates of carriers and hydrogels for controlling the biological half-life of somatostatin and its analogs are disclosed.

The present invention relates to a preparation method of a pharmaceutical composition for delayed release of somatostatin analogues, and to a pharmaceutical composition prepared according to the method. In a preferred aspect, the method comprises the steps of mixing lanreotide acetate with acetic acid, lyophilizing the resulting mixture once, and hydrating the lyophilizate. In the last step of the process, acetic acid can be added to adjust the pH to the desired value.

A pharmaceutical formulation including a chelator-somatostatin receptor ligand and a transchelator is provided. The chelator-somatostatin receptor ligand is conjugated with a metal source or a radionuclide source, whereas the transchelator is capable of capturing free metal source or radionuclide source that is not conjugated to the chelator-somatostatin receptor ligand. By using such pharmaceutical formulation, the preparation of radiolabeled somatostatin analogues could be made more efficient, and is feasible for imaging of SSTR pathway-activated systems in cancers and neurological diseases.

The present invention provides prodrugs of somatostatin peptide and peptide analogs that are tissue permeable and oral bioavailable and enable activity of the somatostatin analog at the circulation or target tissue after cleavage of charge-masking lipophilic moieties. Pharmaceutical compositions comprising these prodrugs and their use in therapy and diagnosis are also provided.

The invention relates to a process for the preparation of injectable pharmaceutical compositions for the sustained release of somatostatin analogues and to pharmaceutical compositions prepared according to the process. In a preferred aspect the process comprises the steps of combining lanreotide acetate and acetic acid, lyophilizing the resulting mixture only once, and hydrating the lyophilizate. Acetic acid may be added to a desired pH during the final step of the process.

The invention relates to a pharmaceutical composition, particularly to a pharmaceutical composition with antitumor activity. The pharmaceutical composition with antitumor activity comprises 5,6-dimethylxanthenone-4-acetic acid (DMXAA) or an pharmaceutically acceptable salt or ester thereof and one drug component selected from glycopeptide antibiotics, actinomycins, mitomycins, glucoside antibiotics, Colchicum alkaloid, elemenes, aromatic enzyme inhibitors, LH-RH receptor antagonists, animal antitumor drugs and somatostatin analogues. The synergic composition has better antitumor activity. More specifically, the invention provides an application of the composition in treating tumors.

The object of the present invention is to provide a kind of somatostatin analog, described somatostatin analog is the aminoacid sequence Hynic-D-Phe-cyclo[Cys-Tyr-D-Trp-Lys-Thr-Cys]-Thr-NH 2 ; Somatostatin analog molecular formula is C 55 h 70 N 14 o 12 S 2 . The present invention also provides a preparation method for the above-mentioned somatostatin analogue or its analogue, which is synthesized by 9-fluorenylmethoxycarbonyl solid-phase synthesis (FMOC-SPPS) method or Fmoc-tBu solid-phase synthesis method. described in the present invention 99m Tc-labeled somatostatin analogs have a high labeling rate and high stability, and can be directly labeled. Cell experiments and rat experiments have proved that the labeling of the present invention can intuitively reflect the tumor location of each organ, and the results are accurate. .