The present invention relates to the field of neurological diseases, particularly to neurodegenerative diseases caused by dipeptide repeat toxicity. The invention provides genetic and chemical inhibitors of the protein kinase NEK6 to treat amyotrophic lateral sclerosis and frontotemporal dementia.

A method of treating or preventing vascular calcification in a patient by administering L-ascorbic acid or ascorbate to the patient and a pharmaceutical composition containing at least one statin and L-ascorbic acid or ascorbate in a dosage form that allows for the concomitant administering of the at least one statin and L-ascorbic acid or ascorbate to a patient.

A method of treating or preventing vascular calcification in a patient by administering L-ascorbic acid or ascorbate to the patient and a pharmaceutical composition containing at least one statin and L-ascorbic acid or ascorbate in a dosage form that allows for the concomitant administering of the at least one statin and L-ascorbic acid or ascorbate to a patient.

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)

##STR00002##

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.).

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)

##STR00002##

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.).

The present invention relates to an inhibitory agent of membrane fusion between a virus envelope and a cell membrane of a host cell for the virus, wherein the inhibitory agent comprises a serine protease inhibitor, and a therapeutic agent or a therapeutic composition, comprising the inhibitory agent. More specifically, the present invention relates to the inhibitory agent, wherein the serine protease inhibitor is one or more of a compound represented by the following general formula (I) or a salt thereof, or a solvate or hydrate thereof, and a therapeutic agent or a therapeutic composition, comprising the inhibitory agent:

##STR00001## wherein R.sub.1 represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group, or a substituted or unsubstituted aromatic heterocyclic group, each of which may optionally comprise a heteroatom.

The present invention relates to an inhibitory agent of membrane fusion between a virus envelope and a cell membrane of a host cell for the virus, wherein the inhibitory agent comprises a serine protease inhibitor, and a therapeutic agent or a therapeutic composition, comprising the inhibitory agent. More specifically, the present invention relates to the inhibitory agent, wherein the serine protease inhibitor is one or more of a compound represented by the following general formula (I) or a salt thereof, or a solvate or hydrate thereof, and a therapeutic agent or a therapeutic composition, comprising the inhibitory agent:

##STR00001## wherein R.sub.1 represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkenyl group, a substituted or unsubstituted aromatic hydrocarbon group, or a substituted or unsubstituted aromatic heterocyclic group, each of which may optionally comprise a heteroatom.

A pharmaceutical composition, comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) compound represented by the following structural formula

##STR00001## at least one acidifying agent; and a vehicle base comprising at least one pharmaceutically acceptable non-aqueous solvent. Values and preferred values of the variables in structural formula (I) are defined herein.

A pharmaceutical composition, comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) compound represented by the following structural formula

##STR00001## at least one acidifying agent; and a vehicle base comprising at least one pharmaceutically acceptable non-aqueous solvent. Values and preferred values of the variables in structural formula (I) are defined herein.

The present invention aims to provide a vaccine pharmaceutical composition universally usable for induction of cellular immunity against various antigens and exerting a high cellular immunity inducing effect. The present invention relates to a vaccine pharmaceutical composition for inducing cellular immunity, containing: an antigen; and a first cellular immunity induction promoter that is a bisphosphonate.