The present invention relates to a hypoxia-inducible factor (HIF) activator, or a pharmaceutically acceptable salt or solvate thereof, for use in promoting tissue repair. The HIF activator, or the pharmaceutically acceptable salt or solvate thereof, is for use with a prototypical tissue-protective cytokine, or a pharmaceutically acceptable salt or solvate thereof, which is administered exogenously to the body being treated.

Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock, culminating in growth retardation and mortalities. Disclosed herein are inhibitors against the enzymatic activity of recombinant CpLDH protein that were identified. The inhibitors were tested for anti-Cryptosporidium effect using in vitro infection assays of HCT-8 cells monolayers. Compounds NSC158011 and NSC10447 were identified to inhibit the proliferation of intracellular C. parvum in vitro, with IC50 values of 14.88 and 72.65 μM, respectively. At doses tolerable in mice, both NSC158011 and NSC10447 significantly reduced the shedding of C. parvum oocysts in infected immunocompromised mice's feces and prevented intestinal villous atrophy as well as mucosal erosion due to C. parvum. These findings have unveiled anti-Cryptosporidium drug candidates that can be explored further for the development of therapeutic agents against C. parvum infections.

Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock, culminating in growth retardation and mortalities. Disclosed herein are inhibitors against the enzymatic activity of recombinant CpLDH protein that were identified. The inhibitors were tested for anti-Cryptosporidium effect using in vitro infection assays of HCT-8 cells monolayers. Compounds NSC158011 and NSC10447 were identified to inhibit the proliferation of intracellular C. parvum in vitro, with IC50 values of 14.88 and 72.65 μM, respectively. At doses tolerable in mice, both NSC158011 and NSC10447 significantly reduced the shedding of C. parvum oocysts in infected immunocompromised mice's feces and prevented intestinal villous atrophy as well as mucosal erosion due to C. parvum. These findings have unveiled anti-Cryptosporidium drug candidates that can be explored further for the development of therapeutic agents against C. parvum infections.

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.).

A method of neutralizing or mitigating a drug-induced mitochondrial dysfunction or impairment for an individual, the method including providing to the individual an effective amount of a composition containing glycine or a functional derivative thereof and N-acetylcysteine or a functional derivative thereof. The drug-induced mitochondrial dysfunction or impairment is from at least one drug consumed by the individual selected from the group consisting of an anticonvulsant; a psychotropic other than an antipsychotic drug; an analgesic/anti-inflammatory drug other than acetaminophen; an antibiotic; an anti-arrhythmic drug; a steroid; a beta-blocker; and an immunization.

A method of neutralizing or mitigating a drug-induced mitochondrial dysfunction or impairment for an individual, the method including providing to the individual an effective amount of a composition containing glycine or a functional derivative thereof and N-acetylcysteine or a functional derivative thereof. The drug-induced mitochondrial dysfunction or impairment is from at least one drug consumed by the individual selected from the group consisting of an anticonvulsant; a psychotropic other than an antipsychotic drug; an analgesic/anti-inflammatory drug other than acetaminophen; an antibiotic; an anti-arrhythmic drug; a steroid; a beta-blocker; and an immunization.

The present invention deals with innovative compounds and compositions for preventing and/or treating a newly discovered detrimental mechanism, which blocks the endogenous myelin repair capacity of the adult nervous system (NS) in diseases associated with the expression of HERV-W envelope protein (ENV), in particular of its MSRV subtype.

The present invention deals with innovative compounds and compositions for preventing and/or treating a newly discovered detrimental mechanism, which blocks the endogenous myelin repair capacity of the adult nervous system (NS) in diseases associated with the expression of HERV-W envelope protein (ENV), in particular of its MSRV subtype.

The present invention deals with innovative compounds and compositions for preventing and/or treating a newly discovered detrimental mechanism, which blocks the endogenous myelin repair capacity of the adult nervous system (NS) in diseases associated with the expression of HERV-W envelope protein (ENV), in particular of its MSRV subtype.