Abstract: 7-phenyl-substituted tetracycline compounds which are substantially free of positional isomers, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-phenyl-substituted tetracycline compounds are described. 7-substituted tetracycline compounds which are substantially free of positional isomers, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-substituted tetracycline compounds are described.

Abstract: A method is provided for treatment of an infective condition in a fluid-containing organ having a natural exterior orifice, such as the udder of a milk producing animal or an ear. The method comprises administering an antibacterial agent to the organ via the exterior orifice and administering in combination therapy with the antibacterial agent a second agent that is an anti-inflammatory agent, an analgesic and/or an antipyretic. The antibacterial agent and, optionally, the second agent, are administered as a pharmaceutical composition further comprising a vehicle that comprises an amphipathic oil that is water dispersible and ethanol insoluble, microcrystalline wax and a pharmaceutically acceptable non-aqueous carrier. Also provided is such a composition comprising the antibacterial agent and the second agent.

Abstract: A method for modulating RNA with tetracycline compounds is described.

Abstract: The present invention pertains, at least in part, to novel 9- substituted minocycline compounds. These minocycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression.

Abstract: A pharmaceutical composition is provided comprising a vehicle that comprises (a) an amphipathic oil that is water dispersible and ethanol insoluble, (b) microcrystalline wax, and (c) a pharmaceutically acceptable non-aqueous carrier; and having an antibacterial substance in an antibacterially effective amount stably dispersed in the vehicle. The composition is suitable for administration by intramammary infusion to a milk producing animal for treatment and/or prevention of mastitis or other diseases of the udder, as well as for otic administration for treatment and/or prevention of an ear infection.

Abstract: Disclosed are controlled release dosage forms of pharmaceutical or nutritional agents that are intended for retention in a buccal or sublingual location for administration. The dosage forms are particularly useful for the sustained release administration of drugs that have a limited window of absorption in the gastrointestinal tract and that are minimally, if at all, absorbed mucosally.

Abstract: Compositions and devices including collagen and a metalloprotease inhibitor, and methods of making and using same.

Abstract: A compound of formula (I): 1

Abstract: A device for releasing a therapeutic agent in the body space in the form of a prosthetic joint implant having a first portion such as a stemmed portion for contacting bone tissue in an intramedullary canal of a long bone. The implant has a second portion which extends into the body space such as a joint space. The joint component contains a reservoir filled with a bioabsorbable/resorbable polymer which includes a therapeutic agent. The reservoir is open or in contact with the joint space as the body fluid diffuses in and out of the polymeric device it carries the drug into the joint space.

Abstract: Neonatal mice with classic inherited retinal degeneration (Pdebrd1/Pdebrd1) are disclosed which fail to mount reactive retinal neovascularization in a mouse model of oxygen-induced proliferative retinopathy. Also disclosed is a comparable human paradigm: spontaneous regression of retinal neovascularization associated with long-standing diabetes mellitus which occurs when retinitis pigmentosa becomes clinically evident. Both mouse and human data indicate that reactive retinal neovascularization either fails to develop or regresses when the number of photoreceptor cells is markedly reduced. The results show that a functional mechanism underlying this anti-angiogenic state is failure of the predicted up-regulation of vascular endothelial growth factor (VEGF), although other growth factors may also be involved. Preventive and therapeutic methods useful against both proliferative and degenerative retinopathies are also disclosed.

Abstract: Substituted tetracycline compounds, methods of synthesis, and methods of use are discussed. Tetracyclines useful for treating tetracycline related disorders are also discussed. Intermediates useful for synthesizing other tetracycline compounds are also included.

Abstract: The present invention relates to a method for decreasing elevated serum/plasma LDL-cholesterol levels or LDL-cholesterol levels and CRP levels in a mammal in need thereof. The methods comprises administering an effective amount of a tetracycline formulation. In one embodiment, the tetracycline formulation is a non-antibacterial tetracycline. In another embodiment, the tetracycline formulation is an antibacterial tetracycline at a sub-antibacterial amount.

Abstract: Mucositis is treated and/or prevented by administrating to a patient a formulation containing a tetracycline and at least one cationic polymer and/or mucoadhesive material. The tetracycline may be in the form of a pharmaceutically acceptable salt or a base. The formulations may optionally also contain an antifungal agent to prevent fungal overgrowth due to reduction in the normal oral flora by the tetracycline. The formulation can be formed into liquid or solid dosage forms such as mouth rinse or tablet. Such compositions have the advantage of prolonged retention of the tetracycline in the mucosa of the oral cavity.

Abstract: This invention relates to a method for coating a medical device comprising the steps of applying to at least a portion of the surface of said medical device, an antimicrobial coating layer and a non-pathogenic bacterial coating layer, wherein the antimicrobial and non-pathogenic bacterial coating layers inhibit the growth of pathogenic bacterial and fungal organisms. The non-pathogenic bacterium used in the bacterial coating layer is resistant to the antimicrobial agent. Furthermore, the non-pathogenic bacterium layer includes at least one of the following: viable whole cells, non-viable whole cells, or cellular structures or extracts. The antimicrobial agent and non-pathogenic bacterium are used to develop a kit comprising these compositions in one container or in separate containers. The kit is used to coat a catheter prior to implantation in a mammal.

Abstract: This invention relates to the composition and method of treating arthritis, repairing of articular joint surfaces and the relief of symptoms associated with arthritis. The composition comprises a nitric oxide synthase inhibitor and amino sugars. The nitric oxide synthase inhibitor reduces the level of nitric oxide, the free radical believed responsible for the degradation of articular cartilage. Amino sugars are the building blocks of articular cartilage and have anti-inflammatory actions.

Abstract: The present invention provides an improved methodology by which therapeutically to overcome resistance to tetracycline in living cells including bacteria, parasites, fungi, and rickettsiae. The methodology employs a blocking agent such as C5 ester derivatives, or 6-deoxy 13-(substituted mercapto) derivatives of tetracycline, in combination with other tetracycline-type antibiotics as a synergistic combination of compositions to be administered simultaneously, sequentially or concurrently. In another embodiment, certain novel compositions are provided which may be administered alone against, for example, a sensitive or resistant strain of gram positive bacteria such as S. aureus and E. faecalis. The concomitantly administered compositions effectively overcome the tetracycline resistant mechanisms present such that the cell is effectively converted from a tetracycline-resistant state to a tetracycline-sensitive state.

Abstract: The present invention pertains, at least in part, to novel substituted 4-dedimethylamino tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression.

Abstract: The present invention provides improved chlortetracycline-containing animal feed compositions and processes and apparatuses for their preparation. In certain embodiments, raw fermentation broth comprising chlortetracycline is divided into two portions. The first portion is mixed with a compound that complexes chlortetracycline. The second portion is acidified and the solids are removed. The acidified liquid is treated with a complexing agent to produced a chlortetracycline complex. The first and second portions thus treated are then mixed and the mixture is passed on to a filter press or other means for separation of the solids to produce a wet cake comprising complexed chlortetracycline. In alternative embodiments, the second portion may be acidified and filtered and admixed with the first portion prior to the complexing step. The resulting mixture is passed on to a filter press or other means for separation of the solids.

Abstract: The invention includes new substituted tetracycline-type compounds that exhibit significant antibacterial activity, including against both gram-positive and gram-negative bacteria. It has been found that compounds of the invention are highly active against both gram positive and gram negative tetracycline sensitive and tetracycline resistant bacteria.

Abstract: The present invention provides methods and compositions useful for preventing bacteremia by decolonizing the intestinal tract of a patient. Although the present invention is useful for preventing bacteremia by any Gram-positive bacteria, it is particularly useful against antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide intermediary susceptible Staphylococcus aureus (GISA), and penicillin-resistant Streptococcus pneumoniae (PRSP). Decolonization therapy using the methods and compositions of this invention are also useful for preventing a Gram-negative bacteremia.

Abstract: A method of treating acne in a human in need thereof comprising administering systemically to said human a tetracycline compound in an amount that is effective to treat acne but has substantially no antibiotic activity, without administering a bisphosphonate compound.

Abstract: Compositions useful for treating inflammatory diseases including arthritis are disclosed which comprise cetyl myristoleate compounds or related compounds and at least one compound useful for treatment of inflammatory disease, such as tetracycline compounds, Cox-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, local anaesthetics, chelating agents, matrix metalloprotease inhibitors, inhibitors of inflammatory cytokines, glucosamine, chondroitin sulfate and collagen hydrolysate. Also disclosed are pharmaceutical compositions and methods of treatment for inflammatory disease and local inflammation and dermal irritation. Also disclosed are compositions including tetracycline and at least one compound useful for treatment of inflammatory disease.

Abstract: L-prolyl-L-m-sarcolysyl-L-p-fluorophenylalanine, lower alkyl esters and/or acid addition salts thereof are produced. For this purpose, L-p-fluorophenylalanine with a protected carboxyl group is caused to react with L-m-sarcolysine with a protected amino group preferably with cooling in an anhydrous medium in the presence of dicyclohexylcarbodiimid, L-m-sarcolysyl-L-p-fluorophenylalanine with a protected amino group and a protected carboxyl group being obtained. Then the amino protection group is removed, with formation of L-m-sarcolysyl-L-p-fluorophenylalanine with a protected carboxyl group. The obtained product is caused to react with proline with a protected amino group in the presence of dicyclohexylcarbodiimid. L-prolyl-L-m-sarcolysyl-L-p-fluorophenylalanine with a protected amino group is obtained. Finally, the amino protection group is removed, and optionally the lower alkyl ester group is removed and/or the obtained compound is converted into an acid addition salt.

Abstract: Sulfonated styrene copolymers are useful for inhibiting elastase and/or collagenase and for promoting angiogenesis in a wound, and for controlling biological organisms on a porous surface. Compositions for these uses may include a tetracycline, an amino acid and/or a sulfonated styrene copolymer in salt form, especially an ammonium salt.

Abstract: A treatment for conditions in human beings associated with either or both reactive arthritis or bursitis comprising a combination of acyclovir, minocycline hydrochloride, and metronidazole. An alternate treatment comprises the combination of valacyclovir hydrochloride, minocycline hydrochloride, and metronidazole.

Abstract: The present invention pertains to novel 7,9-substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression.

Abstract: A medicated animal feed additive in a solid particulate or granular form having improved resistance to powdering and good fracture toughness is provided. The animal feed additive according to the present invention does require a compression or compacting step to achieve its solid structural form. The present invention also provides a method of producing animal feed compositions. In a further embodiment, the present invention relates to a method of combating microbial infection in animals comprising orally administering to said animals a prophylactic or therapeutic amount of an animal comestible composition comprising a medicated feed supplement according to the present invention.

Abstract: Therapeutic methods for treatment of age associated memory impairment (AAMI), mild cognitive impairment (MCI), Alzheimer's disease (AD), cerebrovascular dementia (CVD), and related neurodegenerative conditions by administering an agent capable of inhibiting cell cycle progression, comprising administering one or more agents that are capable of inhibiting neuronal cell cycle progression at either an early cell cycle phase or generally, either alone or in combination with one or more agents capable of reducing mitogenic stimulation.

Abstract: The invention provides compositions and methods to deliver an anti-inflammatory composition, e.g., recombinant human interleukin-4 (rhIL-4), to build (or rebuild) bone tissue. The composition is produced from living osteoprogenitor cells (OPCs) or odontoprogenitor cells.

Abstract: A composition is provided for delivering a tetracycline compound to a mammal. The composition includes an antibiotic tetracycline compound and a controlled-release agent having at least one controlled-release agent. The tetracycline compound is associated with the controlled- release matrix to provide a release profile whereby the mammal is treated substantially without antibiotic activity. Methods for treating a mammal with a tetracycline compound and a dosage unit are also provided utilizing the controlled-release tetracycline composition.

Abstract: This invention provides a method for treating or preventing malaria in a subject. The method includes administering to the subject an effective amount of a substituted tetracycline compound, such that malaria is treated or prevented. In one aspect, the invention relates to pharmaceutical compositions which include an effective amount of a tetracycline compound to treat malaria in a subject and a pharmaceutically acceptable carrier. The substituted tetracycline compounds of the invention can be used to in combination with one or more anti-malarial compounds or can be used to treat or prevent malaria which is resistant to one or more other anti-malarial compounds.

Abstract: The invention is method for preventing sepsis-induced ARDS in a mammal in need thereof, the method comprises administering to the mammal a tetracycline compound in an amount that is effective to prevent sepsis-induced ARDS but has substantially no antibiotic activity.

Abstract: The present invention comprises a method for the treatment of cancerous tumors in mammals comprising the administration of an effective amount of an immunostimulator which enhances and potentiates the mammals own immune system to selectively attack and kill the cancerous cells. The immunostimulator, preferably urushiol, is administered in a pharmaceutically acceptable carrier and can be co-administered in conjunction with other immunostimulators, radiation therapy or other cytotoxic anti-cancer agents to further enhance their effect.

Abstract: The invention features methods for the treatment of neuronal disorders using compounds that reduce or inhibit cytochrome c release. The invention also features methods for identifying compounds that reduce or inhibit cytochrome c release for the treatment of neuronal disorders.

Abstract: A treatment for inhibiting microbial or tumor growth is disclosed, which comprises adding to a subject in need of treatment an effective amount of one or more tetracycline derivatives.

Abstract: The present invention relates to a therapeutic agent for ischemia which inhibits apoptosis under ischemic condition. The therapeutic agent of the present invention comprises antibacterial agents of quinolones, quinones, aminoglycosides or chloramphenicol as an active ingredient. Since the invented therapeutic agent improved the viability of cells under hypoxic and hypoglycemic condition, it can be clinically for ischemic diseases such as applied as a potential drug for ischemia-associated infarction and cerebral infarction.

Abstract: Methods and compounds for treating diseases with tetracycline compounds having a target therapeutic activity are described.

Abstract: The present invention provides methods and compositions involving resorbable hemostatic agents that have the essential absence of microfibrillar collagen. Resorbable hemostatic agents of the present invention comprise polyethylene glycol, which controls bleeding in tissue and does not delay or interfere with healing. The resorbable hemostatic agents of the present invention are biodegradable and biocompatible agents that effectively control bleeding in bone and other tissue without interfering with the subsequent healing of the tissue.

Abstract: This invention pertains to therapeutic antibacterial/antifungal-wound healing compositions comprise a therapeutically effective amount of antibacterial agents and/or antifungal agents and/or wound healing composition alone. In one embodiment, the wound healing composition comprises (a) zinc oxide and (b) fat-soluble vitamins. The therapeutic antibacterial/antifungal-wound healing compositions may be utilized in a wide variety of pharmaceutical products. This invention also relates to methods for preparing and using the antibacterial/antifungal-wound healing compositions and the pharmaceutical products in which the therapeutic compositions may be used.

Abstract: A method of reducing or inhibiting mucositis in a patient, which includes administering an inflammatory cytokine inhibitor or a mast cell inhibitor, or a combination thereof, is disclosed.

Abstract: This invention relates to the use of a conjugate comprising an active substance and a native protein which is not recognized as foreign protein for the production of a pharmaceutical preparation for treating and/or diagnosing inflammatory, infectious and/or skin diseases.

Abstract: Nanobacteria contribute to pathological calcification in the human and animal body, including diseases such as kidney stones, salivary gland stones, dental pulp stones and atherosclerosis. The present invention provides methods for sterilizing articles contaminated with nanobacteria. The present invention also provides methods of treating patients infected with nanobacteria. In particular, the present invention provides a method for preventing the recurrence of kidney stones in a patient that has suffered from kidney stones, comprising administration of an antibiotic, a bisphosphonate, or a calcium chelator, either alone or in combination, in an amount effective to inhibit or prevent the growth and development of nanobacteria.

Abstract: The invention relates to compounds that are capable of modulating CD154 mobilization and that are useful for stabilizing the thrombotic and/or coagulation process and/or reducing the activation of cells involved in an inflammatory response. The invention also relates to methods useful for identifying such compounds. The invention also relates to the treatment of platelets for transfusion with metalloproteinase inhibitors to treat or prevent inflammation. The present invention also includes compositions and methods to treat injury and disease related to such biological processes.

Abstract: 7-substituted fused ring tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-substituted fused ring tetracycline compounds are described.

Abstract: The present invention relates to novel chemistries which allow for heretofore unobtainable substituted tetracycline compounds which exhibit significant antibacterial activity. The methods disclosed herein utilize reactive tetracycline-based precursor compounds, reactive organic substituent precursors and transition metal catalysts under conditions such that a tetracycline compound substituted with the desired organic substituent is formed. In one embodiment of the invention, a substituted tetracycline compound may be prepared by combining a reactive tetracycline-based precursor compound such as an arene tetracycline diazonium salt, and a reactive organic substituent precursor, e.g., alkenes, substituted alkenes, vinyl monomers, aromatics and heteroaromatics, in the presence of a transition metal catalyst, such as palladium chloride, under conditions such that a tetracycline compound substituted with the organic substituent is formed.

Abstract: A method is provided for treatment of an infective condition in an udder of a milk producing animal. The method comprises intramammary administration of an antibacterial agent in combination therapy with a selective COX-2 inhibitor in therapeutically effective amounts of each. Also provided is a pharmaceutical composition comprising an antibacterial agent and a selective COX-2 inhibitor, together with one or more excipients, in a dosage form suitable for intramammary administration to a milk producing animal.

Abstract: A method for treating inhalation anthrax is disclosed. The inventive method comprises the use of 2,3-alkylcarbonyloxybenzoic acid and salts thereof in the prevention and treatment of lung damage caused by Bacillus anthracis and toxins produced by the bacterium. The 2,3-alkylcarbonyloxybenzoic acid may be used alone or in combination with other therapeutic agents such as antibiotics.

Abstract: Mucositis is treated and/or prevented by administrating to a patient a rapidly disintegrating solid dosage form comprising a tetracycline. The dosage form may contain another agent such as an NSAID, an inflammatory cytokine inhibitor, a mast cell inhibitor, an MMP inhibitor, an NO inhibitor, or a mixture thereof. The dosage forms may optionally also contain an antifungal agent to prevent fungal overgrowth due to reduction in the normal oral flora by the tetracycline. The tetracycline is preferably one that is poorly absorbed from the gastrointestinal tract. Such compositions have the advantage of treating the entire gastrointestinal tract since the active ingredient is not removed from the tract via absorption. Further, such compositions minimize systemic exposure and accompanying side effects. The compositions can be formulated as solid dosage forms comprising a tetracycline which disintegrates in an aqueous medium or saliva within in a short period, for example, two minutes. .

Abstract: Therapeutic composition having triglyceride blood level lowering activity, total cholesterol blood level lowering activity, LDL blood level lowering activity, HDL blood level raising activity and activity for preventing the common cold and pneumonia. The therapeutic composition is a formulation comprising an antibiotic, preferably a tetracycline, most preferably doxycycline, which optionally has not been chemically modified to eliminate antimicrobial efficacy. The antibiotic is preferably in a liquid vehicle, preferably one that contains at least 20%, most preferably 26% alcohol by volume. The therapeutic composition is preferably in local delivery form and is self-administered orally.

Abstract: The present invention provides compositions and methods for extending the release times and lowering the toxicity of pharmacologically active compounds. The compounds comprise a salt of the pharmacologically active compound with a lipophilic counterion and a pharmaceutically acceptable water soluble solvent combined together to form an injectable composition. The lipophilic counterion may be a saturated or unsaturated C8-C22 fatty acid, and preferably may be a saturated or unsaturated C10-C18 fatty acid. The compounds precipitate in aqueous environments. When injected into a mammal, at least a portion of the composition precipitates and releases the active compound over time. Thus, the composition forms a slowly releasing drug depot of the active compound in the mammal. Therefore, the present invention enables one to provide a controlled dose administration of the active compound for a period of up to 15 days or even longer.