The object of the present invention is to provide a mitochondrial dysfunction improving agent comprising a vitamin K derivative having a high deliverability to mitochondria.

A mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising at least one of a carboxylic acid ester of an active vitamin K represented by a general formula (1) or a salt thereof, and

##STR00001##

(wherein, R.sub.1 and R.sub.2 are a hydrogen atom, respectively, or a substituent selected from glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof; and at least either of R.sub.1 and R.sub.2 is glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof. R.sub.3 is a group represented by a general formula (2), or a general formula (3). n is an integer of 1 to 7)

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a mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising a carboxylic acid ester of an active vitamin K or a salt thereof (in the general formula (1), R.sub.1 and R.sub.2 is a carboxylic acid residue selected from a group consisting of R.sub.4OOCCH.sub.2CH.sub.2CO— and R.sub.4OOCCH.sub.2CH.sub.2CH.sub.2CO—. R.sub.3 represents the above general formula (2) or (3). R.sub.4 is a C1-C3 alkyl group.).

This invention relates to a compound according to general formula (IA), which acts as a selective cysteine protease inhibitor; to a pharmaceutical composition containing one or more of the compound(s) of the invention; to a combination preparation containing at least one compound of the invention and at least one further active pharmaceutical ingredient; and to uses of said compound(s), including the use as a medicament.

##STR00001##

This invention relates to a compound according to general formula (IA), which acts as a selective cysteine protease inhibitor; to a pharmaceutical composition containing one or more of the compound(s) of the invention; to a combination preparation containing at least one compound of the invention and at least one further active pharmaceutical ingredient; and to uses of said compound(s), including the use as a medicament.

##STR00001##

The present invention relates to pharmaceutically acceptable water soluble salts of aldose reductase inhibitors, 2-(8-oxo-7-((5-trifluromethyl)-1H-benzo[d]imidazol-2-yl)methyl)7,8-dihydropyrazin[2,3-d]pyridazin-5-yl)acetic acid and [4-oxo-(5-trifluoromethyl-benzothaiazol-2-yl)methyl)-3,4-dihydro-phthalazin-1-yl]-acetic acid (also known as zopolrestat), pharmaceutical compositions thereof and methods of treating diabetic complications in mammals comprising administering to mammals these salt and compositions.

The present invention relates to pharmaceutically acceptable water soluble salts of aldose reductase inhibitors, 2-(8-oxo-7-((5-trifluromethyl)-1H-benzo[d]imidazol-2-yl)methyl)7,8-dihydropyrazin[2,3-d]pyridazin-5-yl)acetic acid and [4-oxo-(5-trifluoromethyl-benzothaiazol-2-yl)methyl)-3,4-dihydro-phthalazin-1-yl]-acetic acid (also known as zopolrestat), pharmaceutical compositions thereof and methods of treating diabetic complications in mammals comprising administering to mammals these salt and compositions.

Novel direct thrombin inhibitors are provided herein, along with methods for their use as anticoagulants. The direct thrombin inhibitors described herein are useful in treating and/or preventing thromboembolism and bleeding or clotting disorders. Also provided herein are methods for inhibiting thrombin in a cell using the compounds and compositions described herein.

Novel direct thrombin inhibitors are provided herein, along with methods for their use as anticoagulants. The direct thrombin inhibitors described herein are useful in treating and/or preventing thromboembolism and bleeding or clotting disorders. Also provided herein are methods for inhibiting thrombin in a cell using the compounds and compositions described herein.

The present invention relates to the mannose-receptor selective lysinylated cationic amphiphile and a process for preparation thereof. The compounds of the present invention can target DNA vaccines to antigen presenting cells (APCs) such as macrophages and dendritic cells (DCs), via mannose receptors expressed on the cell surface of APCs. The cationic amphiphiles disclosed herein show enhanced cellular and humoral immune response compared to their mannosyl counterparts in genetic immunization in mice. The present invention discloses that immunization with electrostatic complexes (lipoplexes) of DNA vaccines encoding melanoma antigens (gp100 and tyrosinase) and liposome of the presently described novel lysinylated cationic amphiphiles with mannose-mimicking shikimoyl head-groups provides long-lasting (100 days post melanoma tumor challenge) protective immunity in all immunized mice. Cationic amphiphiles with mannose-mimicking shikimoyl head-groups described in the present invention are likely to find future applications in the field of genetic immunization.

The present invention relates to the mannose-receptor selective lysinylated cationic amphiphile and a process for preparation thereof. The compounds of the present invention can target DNA vaccines to antigen presenting cells (APCs) such as macrophages and dendritic cells (DCs), via mannose receptors expressed on the cell surface of APCs. The cationic amphiphiles disclosed herein show enhanced cellular and humoral immune response compared to their mannosyl counterparts in genetic immunization in mice. The present invention discloses that immunization with electrostatic complexes (lipoplexes) of DNA vaccines encoding melanoma antigens (gp100 and tyrosinase) and liposome of the presently described novel lysinylated cationic amphiphiles with mannose-mimicking shikimoyl head-groups provides long-lasting (100 days post melanoma tumor challenge) protective immunity in all immunized mice. Cationic amphiphiles with mannose-mimicking shikimoyl head-groups described in the present invention are likely to find future applications in the field of genetic immunization.

The present invention relates to a new crystal modification of N-(aminoiminomethyl)-2-aminoacetic acid as well as a method for producing this crystal modification.