Patent application number | Description | Published |
20110295225 | METHOD FOR THE PREPARATION OF A HIGH-TEMPERATURE STABLE OXYGEN-CARRIER-CONTAINING PHARMACEUTICAL COMPOSITION AND THE USE THEREOF - A high temperature-stable and highly purified α-α cross-linked tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. The dimeric form of hemoglobin is degenerated and purification processes are performed on red blood cells obtained from whole blood. Controlled hypotonic lysis in an instant cytolysis apparatus prevents the lysis of white blood cells. Nucleic acids from white blood cells and the phospholipids impurities are not detected. The blocking of reactive sulfhydryl groups in hemoglobin by a sulfhydryl reagent is performed in an oxygenated environment. Flowthrough column chromatography is used to remove different plasma protein impurities. N-acetyl cysteine is added to the α-α cross-linked tetrameric hemoglobin solution to maintain a low level of met-hemoglobin. The stabilized hemoglobin is preserved in an infusion bag with aluminum overwrap to prevent formation of inactive met-hemoglobin from oxygen intrusion. The product finds use in tissue oxygenation and cancer treatment. | 12-01-2011 |
20110319332 | TREATMENT METHODS USING A HEAT STABLE OXYGEN CARRIER-CONTAINING PHARMACEUTICAL COMPOSITION - A highly purified and heat stable cross-linked nonpolymeric tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin, uncross-linked tetrameric hemoglobin, and plasma protein impurities effectively. Addition of N-acetyl cysteine after heat treatment and optionally before heat treatment maintains a low level of met-hemoglobin. The heat stable cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. The inventive tetrameric hemoglobin can also be used to prevent tumor metastasis and recurrence following surgical tumor excision. Further the inventive tetrameric hemoglobin can be administered to patients prior to chemotherapy and radiation treatment. | 12-29-2011 |
20110319858 | METHOD FOR THE PREPARATION OF A HEAT STABLE OXYGEN CARRIER-CONTAINING PHARMACEUTICAL COMPOSITIONS AND THE USE THEREOF - A highly purified and heat stable α-α cross-linked tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin and the plasma proteins impurities effectively. Addition of N-acetyl cysteine to the heat stable a-a cross-linked tetrameric hemoglobin maintains a low level of met-hemoglobin. The heat stable a-a cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. Another application is heart preservation in situations where there is a lack of oxygen supply in vivo, such as in heart transplant or oxygen-deprived heart. | 12-29-2011 |
20130059000 | ORAL DELIVERY FOR HEMOGLOBIN BASED OXYGEN CARRIERS - A process for making hemoglobin based oxygen carrier (HBOC) containing pharmaceutical composition suitable for oral delivery and the composition formed thereby are described. There are three exemplary composition configurations which include (1) hemoglobin-loaded nanoparticles solution, (2) enteric-coated hemoglobin capsules and (3) enteric-coated hemoglobin tablets. To facilitate the bioavailability and bio-compatibility of hemoglobin, intestinal absorption enhancers are added in each of the HBOC formulations. Protective layers ensure delivery of an intact hemoglobin structure in intestinal tract without degradation in the stomach. The HBOC formulations may be used for preventive or immediate treatment of high altitude syndrome (HAS) or for treatment of hypoxic conditions including blood loss, anemia, hypoxic cancerous tissue, and other oxygen-deprivation disorders. In addition to delivering oxygen, the heme group of hemoglobin from HBOC formulations can provide heme iron to the human body to aid in the production of more red blood cells. | 03-07-2013 |
20130219829 | METHOD FOR THE PREPARATION OF A HEAT STABLE OXYGEN CARRIER-CONTAINING PHARMACEUTICAL COMPOSITION AND THE USE THEREOF - A highly purified and heat stable cross-linked tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin and the plasma proteins impurities effectively. Addition of N-acetyl cysteine to the heat stable cross-linked tetrameric hemoglobin maintains a low level of met-hemoglobin. The heat stable cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. Another application is heart preservation in situations where there is a lack of oxygen supply in vivo, such as in heart transplant or oxygen-deprived heart. The presently claimed invention also includes a method for preparing a packaged cross-linked tetrameric hemoglobin composition. | 08-29-2013 |
20140106004 | HEMOGLOBIN-BASED OXYGEN CARRIER-CONTAINING PHARMACEUTICAL COMPOSITION FOR CANCER TARGETING TREATMENT AND PREVENTION OF CANCER RECURRENCE - The present invention provides a pharmaceutical composition containing a hemoglobin-based oxygen carrier for treating cancer, preventing recurrence and metastasis of cancerous tumor. The composition can be used alone or in combination with at least one chemotherapeutic agent such as 5FU, Bortezomib, doxorubicin, cisplatin, or any combination thereof. The hemoglobin-based oxygen carrier in the composition is capable of targeting a surface receptor expressed on cancerous cells and facilitating the uptake of both hemoglobin-based oxygen carrier and the chemotherapeutic agent by the cancerous cells via a receptor-mediated mechanism. The hemoglobin-based oxygen carrier inhibits the expression of hypoxic response elements such as HIF1α, VEGF, ET1, VHL, etc. The pharmaceutical composition of the present invention is also useful for inducing the apoptosis or cell death of a type of self-renewing and tumor-initiating cells called cancer stem cells which are located in the hypoxic niche of a cancerous tumor. | 04-17-2014 |
20140255377 | PHARMACEUTICAL COMPOSITION COMPRISING ALBUMIN-BINDING ARGININE DEIMINASE FOR CANCER TARGETING TREATMENT - The present invention provides a pharmaceutical composition containing albumin-binding arginine deiminase fusion protein (AAD) for treating cancer or other arginine-dependent diseases. The AAD fusion protein can be purified from both soluble and insoluble fractions of crude proteins, it binds to human serum albumin (HSA) and has its high activity with longer half life for efficient depletion of arginine in cancer cells. The specific activities of wild-type ADI and AAD in the present invention are 8.4 and 9.2 U/mg (at physiological pH 7.4), respectively. The AAD used in the present invention can be used in the treatment of various cancers (e.g. pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer & brain cancer) and curing arginine-dependent diseases. The composition can be used alone or in combination with at least one chemotherapeutic agent to give a synergistic effect on cancer treatment and/or inhibiting metastasis. | 09-11-2014 |
20140303085 | HEMOGLOBIN-BASED OXYGEN CARRIER-CONTAINING PHARMACEUTICAL COMPOSITION FOR CANCER TARGETING TREATMENT AND PREVENTION OF CANCER RECURRENCE - The present invention provides a pharmaceutical composition containing a hemoglobin-based oxygen carrier for treating cancer, preventing recurrence and metastasis of cancerous tumor. The composition can be used alone or in combination with at least one chemotherapeutic agent such as 5FU, Bortezomib, doxorubicin, cisplatin, or any combination thereof. The hemoglobin-based oxygen carrier in the composition is capable of targeting a surface receptor expressed on cancerous cells and facilitating the uptake of both hemoglobin-based oxygen carrier and the chemotherapeutic agent by the cancerous cells via a receptor-mediated mechanism. The hemoglobin-based oxygen carrier inhibits the expression of hypoxic response elements such as HIF1 α, VEGF, ET1, VHL, etc. The pharmaceutical composition of the present invention is also useful for inducing the apoptosis or cell death of a type of self-renewing and tumor-initiating cells called cancer stem cells which are located in the hypoxic niche of a cancerous tumor. | 10-09-2014 |
20140335018 | PHARMACEUTICAL COMPOSITION COMPRISING MODIFIED HEMOGLOBIN-BASED THERAPEUTIC AGENT FOR CANCER TARGETING TREATMENT AND DIAGNOSTIC IMAGING - The present invention provides a pharmaceutical composition containing hemoglobin-based therapeutic agent for treating cancer. The hemoglobin moiety can target cancer cells and the therapeutic moiety (i.e. active agent/therapeutic drug) can kill the cancer cells efficiently. The hemoglobin-based therapeutic agent used in the present invention can be used in the treatment of various cancers such as pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer and brain cancer. The composition can be used alone or in combination with other therapeutic agent(s) such as chemotherapeutic agent to give a synergistic effect on cancer treatment, inhibiting metastasis and/or reducing recurrence. The presently claimed hemoglobin-based 5FU-two-dye conjugate and/or hemoglobin-based 5FU-one-dye conjugate can also be used in live-cell imaging and diagnostic imaging. | 11-13-2014 |