184 results about "Diketopiperazines" patented technology

A composition is disclosed comprising glucagon-like peptide 1 (GLP-1) particles in combination with diketopiperazine (DKP) that is stable both in vitro and in vivo. The composition has utility as a pharmaceutical formulation for treating diseases such as diabetes, cancers, and obesity but is not limited to such diseases or conditions. In particularly, the composition has utility as a pharmaceutical formulation for pulmonary delivery.

Biologically active agent delivery compositions, which comprise diketopiperazine carboxylate salts are provided. Related methods for making and using the biologically active agent delivery compositions are also provided.

Provided is a method for the synthesis of N-protected bis-3,6-[4-aminobutyl]-2,5-diketopiperazine including the step of heating a solution of c-amino protected lysine in the presence of a catalyst selected from the group consisting of sulfuric acid, phosphoric acid, and phosphorus pentoxide.

Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal of one or more impurities from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and / or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.

The invention relates to two synthetic methods of 3,6-bis(4-bisfumaroyl aminobutyl)-2,5-diketopiperazine and a salt substitute thereof. The first synthetic method comprises the following steps of: obtaining a final product through the steps of cyclodehydration, hydrogenation, coupling, saponification, recrystallization and the like by using epsilon-benzoyloxycarbonyl-L-lysine and p-nitryl monoethyl fumarate as starting materials. The second synthetic method comprises the following steps of: obtaining the final product through the steps of cyclodehydration, coupling, saponification, recrystallization and the like by using N-6-trifluoroacetyl-L-lysine and the p-nitryl monoethyl fumarate (or p-nitryl monoethyl fumarate acyl chloride) as the starting materials. Meanwhile, the salt substitute of the 3,6-bis(4-bisfumaroyl aminobutyl)-2,5-diketopiperazine can also be generated by directly carrying out substitution reaction on the 3,6-bis(4-bisfumaroyl aminobutyl)-2,5-diketopiperazine as a reaction product and corresponding salt.

Compositions and methods have been developed for transporting compounds across membranes with little or no toxicity and, when targeted through the appropriate routes of administration (i.e., lung, gastrointestinal (GI) tract), little or no immune stimulation. The compositions can mediate cellular delivery of compounds that would otherwise not enter cells and enhance the intracellular delivery of compounds that would otherwise enter cells inefficiently. The methods are carried out by contacting a proximal face of a lipid bilayer or membrane (e.g. the surface of an intact cell) with a complex containing a compound (e.g., a therapeutic agent) and a diketopiperazine (DKP). DKP and the compound are non-covalently associated with each other or covalently bound to each other.

Compositions containing biologically active molecules encapsulated in self-assembling, diketopiperazine microspheres (TECHNOSPHEREs™) and methods for making and administering such compositions are described herein. The compositions can be used to immunize individuals against agents of biological warfare. The biologically active molecules include atropine, antibodies, antigens, and antibiotics. The compositions can be placed in an inhalation device for self-administration. Pulmonary delivery of TECHNOSPHERE™ encapsulated atropine, antibodies, vaccines, and antibiotics provides an accelerated onset of immunity to the targeted disease. Furthermore, the TECHNOSPHERE™ encapsulated atropine, antibodies, vaccines, and antibiotics are stable formulations, suitable for stockpiling, rapid dissemination and mass treatment.

The present invention relates to the diagnosis and monitoring of diseases and conditions by quantifying markers, including degradation products of disease-associated proteins, such as diketopiperazines composed of the two N-terminal amino acids or the two C-terminal amino acids of such proteins. The methods are useful for diagnosing or monitoring various diseases, including multiple sclerosis, Alzheimer's disease and ischemia. The invention further provides binding partners specific for the markers and compositions and kits for conducting the methods of the invention.

Methods are provided for purifying peptides and proteins by incorporating the peptide or protein into a diketopiperazine or competitive complexing agent to facilitate removal one or more impurities, from the peptide or protein. Formulations and methods also are provided for the improved transport of active agents across biological membranes, resulting for example in a rapid increase in blood agent concentration. The formulations include microparticles formed of (i) the active agent, which may be charged or neutral, and (ii) a transport enhancer that masks the charge of the agent and / or that forms hydrogen bonds with the target biological membrane in order to facilitate transport. In one embodiment, insulin is administered via the pulmonary delivery of microparticles comprising fumaryl diketopiperazine and insulin in its biologically active form. This method of delivering insulin results in a rapid increase in blood insulin concentration that is comparable to the increase resulting from intravenous delivery.

The present invention relates to compounds to inhibit blood coagulation, and more particularly to novel diketopiperazine derivatives, pharmaceutically acceptable salts and compositions thereof, to specifically inhibit thrombin. The compound has the following general structure wherein R1, R2 and R4 consist of a hydrogen, alkyl or aryl moiety, R3 consist of an alkyl or aryl moiety, wherein R5 consists of a hydrogen, alkyl, aryl, hydroaryl, heteroaryl, hydroheteroaryl, sulfonylalkyl, sulfonylaryl, sulfonylhydroaryl, sulfonylheteroaryl or sulfonylhydroheteroaryl moiety, and wherein R6 consists of a hydrogen, alkyl, aryl, hydroaryl, heteroaryl or hydroheteroaryl moiety. Also disclosed are methods of using the compound for treating coagulation disorders such as thrombosis and heparin associated thrombocytopenia.

Drug delivery to the pulmonary system has been achieved by encapsulation of the drug to be delivered in microparticles having a size range between 0.5 and ten microns, preferably in the range of two to five microns, formed of a material releasing drug at a pH of greater than 6.4. In a preferred embodiment, the drug delivery system is based on the formation of diketopiperazine microparticles which are stable at a pH of 6.4 or less and unstable at pH of greater than 6.4, or which are stable at both acidic and basic pH, but which are unstable at pH between about 6.4 and 8. Other types of materials can also be used, including biodegradable natural and synthetic polymers, such as proteins, polymers of mixed amino acids (proteinoids), alginate, and poly(hydroxy acids). In another embodiment, the microparticles have been modified to effect targeting to specific cell types and to effect release only after reaching the targeted cells.

The invention provides a method of inhibiting vascular hyperpermeability in an animal in need thereof. The method comprises administering an effective amount of a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazine has the formula set forth in the specification.The invention also provides a method of modulating the cytoskeleton of an endothelial cell in an animal. The method comprises administering an effective amount of a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazine has the formula set forth in the specification.The invention further provides a kit. The kit comprises a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal, wherein the diketopiperazine has the formula set forth in the specification.

The present invention relates to the diagnosis and monitoring of diseases and conditions by quantifying markers, including degradation products of disease-associated proteins, such as diketopiperazines composed of the two N-terminal amino acids or the two C-terminal amino acids of such proteins. The methods are useful for diagnosing or monitoring various diseases, including multiple sclerosis, Alzheimer's disease and ischemia. The invention further provides binding partners specific for the markers and compositions and kits for conducting the methods of the invention.

The invention provides a method of synthesizing a diketopiperazine of the formula: wherein:R1 is —CH2COR3, or —CH2CH2COR3;R2 is the side chain of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, cysteine, methionine, norvaline and ornithine;R3 is —OH, —NH2, —OR4, —NHR4, or —NR4R4; andeach R4 is independently an alkyl, aryl, alkylaryl, or arylalkyl.

This disclosure provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the disclosure is concerned with diketo piperazine and piperadine derivatives that possess unique antiviral activity. More particularly, the present disclosure relates to compounds useful for the treatment of HIV and AIDS.

This disclosure provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the disclosure is concerned with diketo piperazine and piperadine derivatives that possess unique antiviral activity. More particularly, the present disclosure relates to compounds useful for the treatment of HIV and AIDS.

The invention provides (i) a method of treating metabolic syndrome in an animal, (ii) a method of suppressing the appetite of an animal, (iii) a method of treating obesity in an animal, (iv) a method of reducing the weight of an animal in need thereof, (v) a method of reducing a blood lipid level in an animal in need thereof, (vi) a method of treating non-alcoholic steatohepatitis in an animal, and (vii) a method of inhibiting adipogenesis. The methods comprise administering an effective amount of an active ingredient, wherein the active ingredient comprises a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal. The invention also provides a kit comprising a container holding a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them; and instructions for administration. The diketopiperazines have the formula given in the application.

Feed additives containing essential amino acids which are diketopiperazines of formulas (IV) or (V) or salts thereof are provided:In formulas (IV) and (V), R1 and R2 may be an amino acid residue such as methionine, lysine, threonine, tryptophan, histidine, valine, leucine, isoleucine, phenylalanine, arginine, and cysteine, and may optionally be the same residue.Additionally provided are the diketopiperazines of formulas (IV) and (V) and a method to for their production.

The invention provides a method of treating rhinitis. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP) formulated for nasal administration. The invention also provides a pharmaceutical product comprising a DA-DKP containing composition.

The invention belongs to the technical field of organic compound synthesis and relates to a preparation method of fine glufosinate, in particular to a preparation method of fine glufosinate with L-homoserine as a raw material. According to the preparation method of fine glufosinate, L-homoserine prepared through a biological fermentation method serves as an initial raw material, L-3,6-di(2-halogenethyl)-2,5-diketopiperazine is prepared through the steps such as azeotropic dehydration and halogenation, a Serhiy Arbuzov reaction is conducted between L-3,6-di(2-halogen ethyl)-2,5-diketopiperazine and methyl phosphonic acid dibutyl, and fine glufosinate is prepared through a hydrolysis reaction. Compared with an existing preparation technology, the preparation method of fine glufosinate has the advantages that the total yield of fine glufosinate is greatly increased, the technological process is simple, and fine glufosinate is suitable for industrial production.

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP.

A process is described for preparing stabilized tablet formulations for temperature and moisture sensitive active drugs. Water soluble polyvinyl alcohol is processed with drugs such as angiotensin converting enzyme (ACE) inhibitors and compressed into solid form once excess water is removed. Low dose polyvinyl alcohol ramipril tablets prepared by this process are stable under conditions of high humidity and heat for periods of at least up to six months with less than 8% hydrolysis of the prodrug to the active metabolite diketopiperazine (DKP).

The invention provides a method of treating a degenerative joint disease. The method comprises administering an effective amount of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a pharmaceutical product as well as a kit comprising DA-DKP.

The present invention provides a method of modulating various aspects of the immune system. In particular, the present invention teaches the use of diketopiperazines (DKPs) to modulate various aspects of the immune system such as, for example, inflammation, T-cells and various cytokines.

The invention provides (i) a method of treating metabolic syndrome in an animal, (ii) a method of suppressing the appetite of an animal, (iii) a method of treating obesity in an animal, (iv) a method of reducing the weight of an animal in need thereof, (v) a method of reducing a blood lipid level in an animal in need thereof, (vi) a method of treating non-alcoholic steatohepatitis in an animal, and (vii) a method of inhibiting adipogenesis. The methods comprise administering an effective amount of an active ingredient, wherein the active ingredient comprises a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal. The invention also provides a kit comprising a container holding a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them; and instructions for administration. The diketopiperazines have the formula given in the application.

The present invention relates to compositions containing the fungus Alternaria alternata and, or the secondary metabolites thereof, belonging to the family of the diketopiperazines (DKPs), for controlling the pathogen fungus Plasmopara viticola.

A breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system are provided. The dry powder inhaler can be provided with or without a unit dose cartridge for using with the inhaler. The inhaler and / or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient, including, peptides and proteins such as insulin and glucagon-like peptide 1 for the treatment of diabetes and / or obesity. The dry powder inhaler is compact; can be provided in various shapes and sizes, colors, and comprises a housing, a mouthpiece, a cartridge placement area, and a mechanism for opening and closing the medicament cartridge. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable.

The present invention relates to the contacting of one or more surfaces of an implantable medical device with one or more diketopiperazines (DKPs).