223 results about "Systemic toxicity" patented technology

The invention relates to molecules inhibiting biologically active compounds and further comprising moieties specifically cleavable by a reagent produced by a target cell. The invention relates to inhibitors that bind, inhibit, suppress, neutralize, or decrease activity of a biologically active agent. Inhibitors comprise at least one moiety that bind, inhibit, suppress, neutralize, or decrease activity of a biologically active agent and at least one moiety that can be cleaved specifically by a reagent produced by target cells. The cleavage deactivates the inhibitor. Following cleavage, the active agent is liberated into the local environment. Administration of the inhibitor alone or together with the active agent suppress the compound's activity until it reaches the proximity of a target cell. Targeted specific release enables the agent concentration in specific site to reach levels that have desired therapeutic effects without systemic toxicity.

An improved method and products for the primary hormonal treatment of early stage, low and intermediate risk prostate cancers by prostatic implants of androgen suppressive drugs formulated as fused with a lipoid carrier or encapsulated in microcapsules or in Silastic capsules is provided. Such prostatic implants renders a constant slow-release of their contents to the prostate for extended periods by biodegradation and diffusion. It facilitates higher prostatic and lower systemic concentrations of androgen suppressive hormones. Because of their high prostatic and lower systemic concentrations, tumor control is much improved and the their systemic toxicity is minimized. Tumor control after such primary hormonal implant treatment is followed by clinical examinations and the biochemical tumor control is followed by periodic estimations of serum levels of PSA and acid phosphatase. More complex and expensive surgery or radiation therapy for this group of good prognostic early stage prostate cancer is reserved for those patients failing to this primary hormonal treatment. It will preserve potency more than by surgery or radiation therapy. Furthermore, it would reduce the cost of treatment for early stage prostate cancer significantly. Androgen suppressive hormonal implants to the prostate before, during or after lower dose conventional radiation therapy would also facilitate equal or better cure rates of localized prostate cancer as compared to the more complex and toxic higher dose radiation therapy.

The topical medicament gel formulation of the present invention includes an anesthetic, an anti-microbial, an oxidant, a nutrient, a diuretic, an opioid, an anti-emetic, an anti-seizure drug, and a non-steroidal anti-inflammatory drug (NSAID), USP in a molecular, as opposed to a salt form, as the active ingredient. Additional constituents illustratively include a skin penetration enhancer and a gelling agent. This invention deals with problems commonly associated with topical application of local medicaments such as: slow onset of action; need for occlusion; and rapid loss of effect due to rapid systemic dispersion. The invention permits enhanced penetration of the medicament and thereby allows for a lesser total dosage of pharmaceutically active ingredient. The use of a lesser total dosage also decreases systemic toxicity.

A drug and drug delivery system may be utilized in the treatment of vascular disease. A local delivery system is coated with rapamycin or other suitable drug, agent or compound and delivered intraluminally for the treatment and prevention of neointimal hyperplasia following percutaneous transluminal coronary angiography. The local delivery of the drugs or agents provides for increased effectiveness and lower systemic toxicity.

Bacteria which co-express protease inhibitors and protease sensitive therapeutic agents, which are surface displayed, secreted and/or released and result in their localized production and maintenance within a target tissue and inactivation outside of the target tissue, thereby increasing therapeutic activity and reducing the systemic toxicity. The bacteria may be attenuated, non-pathogenic, low pathogenic or a probiotic. Protease sensitivity may be further accomplished by engineering protease degradation sites within the therapeutic agents, further enhancing the inactivation outside of the target tissue while retaining activity within the target tissue through co-expression of a protease inhibitor. Novel chimeric proteins secreted by bacteria, including chimeric toxins targeted to neoplastic cells, tumor matrix cells and cells of the immune system, and combination therapies of these protease inhibitor:chimeric toxin-expressing bacteria together with small-molecule and biologic agents are also described. Non-conjugative bacteria limiting exchange of genetic material, and antibody resistant bacteria are also provided.

The present invention uses co-expression of protease inhibitors and protease sensitive therapeutic agents that results in their localized production within the target tissue and inactivation outside of the target tissue, thereby increasing therapeutic activity and reducing the systemic toxicity. Inactivation is also accomplished by engineering protease degradation sites within the therapeutic construct for proteases, preferably those that are under-expressed within the target tissue yet present in non-target tissues within the body, resulting in therapeutic activity within the target tissue and inactivation outside of the target tissue. Novel chimeric proteins secreted by bacteria are also described. The chimeric proteins include chimeric toxins targeted to neoplastic cells and cells of the immune system. Novel combination therapies of these protease inhibitor:chimeric toxin-expressing bacteria together with small-molecule and biologic agents are also described. Non-conjugative bacteria capable of delivering phage/phagemids expression cassettes for DNA and RNA-based therapeutics are also described.

The invention relates to biocompatible, bioabsorbable derivatized non-crosslinked chitosan compositions optionally crosslinked to gelatin/collagen by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) for biomedical use and methods of making and testing such compositions, including a modified acute systemic toxicity test. The compositions comprise derivatized chitosan reacetylated to a degree of N-deacetylation (DDA) of between about 15% and 40%. The compositions are typically bioabsorbed in about 90 days or less and can be made to bioabsorb at differing rates of speed. The compositions are initially soluble in aqueous solution below pH 6.5. The compositions have an acid content that can be adjusted between about 0% (w/w) and about 8% (w/w) to customize the composition for uses that require and/or tolerate differing levels of cytotoxicity, adhesion, composition cohesion, and cell infiltration into the composition.

Fluidic multiwell bioreactors are provided as a microphysiological platform for in vitro investigation of multi-organ crosstalks for an extended period of time of at least weeks and months. The disclosed platform is featured with one or more improvements over existing bioreactors, including on-board pumping for pneumatically driven fluid flow, a redesigned spillway for self-leveling from source to sink, a non-contact built-in fluid level sensing device, precise control on fluid flow profile and partitioning, and facile reconfigurations such as daisy chaining and multilayer stacking. The platform supports the culture of multiple organs in a microphysiological, interacted systems, suitable for a wide range of biomedical applications including systemic toxicity studies and physiology-based pharmacokinetic and pharmacodynamic predictions. A process to fabricate the disclosed bioreactors is also provided.

The invention relates to a preparation method of a biological ceramic coating rich in calcium and phosphate phases on the surface of magnesium alloy, comprising the following steps of: adding (C6H5O7)2Ca3.4H2O and Na3PO4 to deionized water, and simultaneously adding KOH, NH4HF2, N(CH2CH2OH)3, C3H8O3 and H2O2 to prepare an electrolyte with a certain concentration ratio of calcium and phosphate; disposing the magnesium alloy in the electrolyte as an anode which is prepared through micro arc oxidation energization reaction. The calcium-phosphate ceramic coating obtained by the preparation methodconsists of three layers of a loose layer, a transition layer and a compact layer, wherein the surface of the loose layer consists of a plurality of uniformly distributed micropores, the transition layer is between the loose layer and the compact layer, and the compact layer and a substrate body form good metallurgical bonding; therefore, the coating has high rigidity, high density, high bonding force and good corrosion resistance and abrasion resistance; simultaneously, the mouse acute systemic toxicity test indicates that the coating has good biocompatibility, and the simulated body fluid soaking test indicates that the coating has good biological activity.

The invention provides a device, method, system and program for intelligent in vivo cell-level chemical or genetic material delivery; wherein multiple injectable biocompatible physical delivery device containers are used to selectively administer medicine, chemical(s) or genetic materials to a target cell in a patient, human or animal, with reduced systemic toxicity; said delivery device container includes an internal contents-to-cell transfer mechanism, usually a syringe; a biological “key” molecule, magnetic device or vibration frequency signature sensor placed on the surface of the delivery device container which is adapted to selectively bind to said target cell directly or indirectly; a “tag” placed on the surface of the delivery device container, usually metallic and biocompatible in nature, which will display to an observer when scanned through external devices such as x-ray, MRI, CT, sound, etc.; and a release mechanism to move the internal contents of the delivery device container into said target cell over a predetermined and specified timed basis.

The invention discloses a preparation method and application of metal organic framework drug carrier system based on drug cytosine arabinoside micromolecule prodrug. The preparation method disclosed by the invention comprises the steps: choosing molecules which can generate coordination reaction with metal ions to be covalently combined with cytosine arabinoside to synthesize novel multifunctionalmicromolecule prodrug; carrying the prodrug on the metal organic framework through a simple environment-friendly one-step entrapment method to form medicine carrying nanoparticles; centrifuging, washing and drying to obtain a cytosine arabinoside micromolecule prodrug carrying MOF intravenous injection preparation. Taking synthesized Ara-IR820@ZIF-8 as an example, a mouse in-vivo antitumor pharmacological result shows that HA/Ara-IR820@ZIF-8 nano water solution has a good antitumor effect and lower system toxicity. The intravenous injection preparation has the advantages of high medicine carrying amount, simple and economic preparation process, batch production, small toxicity, good safety and wide application prospect in achieving high medicine carrying amount of the cytosine arabinosidein the metal organic framework and applying intravenous injection dosage to treat solid tumors.

A drug and drug delivery system may be utilized in the treatment of vascular disease. A local delivery system is coated with rapamycin or other suitable drug, agent or compound and delivered intraluminally for the treatment and prevention of neointimal hyperplasia following percutaneous transluminal coronary angiography. The local delivery of the drugs or agents provides for increased effectiveness and lower systemic toxicity.

A drug and drug delivery system may be utilized in the treatment of vascular disease. A local delivery system is coated with rapamycin or other suitable drug, agent or compound and delivered intraluminally for the treatment and prevention of neointimal hyperplasia following percutaneous transluminal coronary angiography. The local delivery of the drugs or agents provides for increased effectiveness and lower systemic toxicity.

The present invention concerns compositions and methods of use of a humanized Class III anti-CEA antibody, comprising the heavy and light amino acid sequences SEQ ID NO:1 and SEQ ID NO:2. The antibody is effective to treat CEACAM5-expressing tumors, either alone or in combination with one or more therapeutic agents. Drug conjugated Class III anti-CEA antibodies, such as SN-38 or P2PDox immunoconjugates, are particularly efficacious. Surprisingly, the antibody-drug conjugates (ADCs) exhibit high anti-cancer efficacy, while exhibiting low levels of systemic toxicity that are readily treated with standard amelioration techniques. Antibodies and/or immunoconjugates comprising the amino acid sequences SEQ ID NO:1 and SEQ ID NO:2 are surprisingly efficacious for therapy of solid tumors, even when the tumor has proven resistant to standard anti-cancer therapies.

The subject invention provides a mechanism by which steroidal quinol compounds confer beneficial ophthalmic effects. The subject compounds possess a lipophilic-hydrophilic balance for transcorneal penetration and are readily reduced into parent phenolic A-ring steroid compounds to provide protection or treatment against various ocular symptoms and disorders. The compounds according to the subject invention appear to be highly advantageous as prodrugs to provide protection and/or treatment against ocular disorders. These prodrugs confer lipid solubility optimal for transocorneal penetration and are readily converted to endogenous reducing agents into active phenolic A-ring steroid compounds. To the extent that these prodrugs have reduced feminizing effects and systemic toxicity, they would be expected to be quite advantageous for protecting or treating the eye against ocular disorders such as cataract or glaucoma without undesired (systemic) side effects).

The invention relates to the technical field of medicines, and provides a docetaxel and sulforaphane loaded hyaluronic acid modified poly(lactic-co-glycolic acid) copolymer self-assembled nano-particle, a preparation method thereof and an application of the self-assembled nano-particle in preparing a medicine for treating breast cancer. The microscopic structure of the nano-particle comprises a hydrophobic PLGA (poly(lactic-co-glycolic acid)) core and a hydrophilic HA (hyaluronic acid) shell, wherein the PLGA core is used for wrapping a medicine DTX (docetaxel) or SFN (sulforaphane), and the hydrophilic shell HA can target a breast cancer stem cell highly expressing a CD44 receptor. In-vitro cytotoxicity tests indicate that the drug-loaded nano-particle can play a good role in resisting differentiation of mammary gland cells and breast cancer stem cells when compared with free medicines; in-vivo tumor inhibition experiments indicate that the drug-loaded medicine is more effective than free medicines and combined free medicines, and has a small systematic toxicity. The nano-particle can play a role in simultaneously performing target differentiating on mammary gland cells and breast cancer stem cells, and a new strategy is provided to treatment of breast cancer.

The topical anesthetic formulation of the present invention is typically a solution that preferably includes lidocaine, USP as the active anesthetic ingredient with benzyl alcohol and isopropyl alcohol. This invention deals with problems commonly associated with topical application of local anesthetics such as: slow onset of action; need for occlusion; messiness of creams, ointments or gels; and rapid loss of effect due to rapid systemic dispersion. The invention permits enhanced penetration of the anesthetic and thereby allows for a lesser total dosage of pharmaceutically active ingredient. The use of a lesser total dosage also decreases systemic toxicity.

The invention discloses a pro-drug as shown in general formula (I), which is formed by coupling camptothecin or a derivative of the camptothecin with non-linear configuration glycol polyethylene, wherein, the definition for varied groups is available in the specification. A physiological disposition research on nude mice discloses that: the pro-drug has a time-delay plasma concentration - time curve, and the plasma concentration can still be maintained at over 100ng/ml 72 hours after intravenous medication. Evaluation on physiological drug effect shows that the pro-drug has strong growth inhibiting effect against the LOVO HCT116 cell line transplantable tumor inoculated into the nude mice and also has obvious growth inhibitory activity against human lung carcinoma H460 cell line transportable tumor inoculated into the nude mice. The inhibition of the pro-drug is better than that of Irinotecan, a positive control drug and has no obvious systemic toxicity.

The invention discloses a tumor-targeted delivery carrier based on cell-derived micro-vacuoles, a preparation method and an application. The preparation method comprises the following steps of: (A) preparing a conditioned medium: supplementing fetal bovine serum, antibiotics, DSPE-PEG-Biotin and DSPE-PEG-Folate into a basal medium; (B) using the obtained conditioned medium in cell culture, and collecting cell culture supernatant for subsequent separation; (C) carrying out low-speed centrifugation on the obtained culture supernatant to remove cell debris and apoptotic bodies, then adding SA-IONPs, mixing uniformly, incubating, then separating by a magnet, using PBS for re-suspension, eluting for multiple times to obtain the cell-derived micro-vacuoles with membrane surfaces modified by folic acid and iron oxide nano-particles, and freezing for storage; and (D) loading chemotherapeutic drugs or therapeutic genes into the functionalized micro-vacuoles doubly-modified by an electroporation mode, and carrying out re-suspension after separation with the magnet. The tumor-targeted delivery carrier based on cell-derived micro-vacuoles, the preparation method and the application disclosed by the invention are applicable to specific targeting delivery of multiple chemotherapeutic drugs and therapeutic genes, and have the advantages of enhancing the anti-tumor effect, reducing the systemic toxicity and improving the clinical effect of the current therapeutic selection, so that a new hope is brought for clinical therapy of tumors.