A compound which is a thienolate of formula (I) or a pharmaceutically acceptable salt thereof: (I) wherein R.sup.1, R.sup.3, Ring A1, n and Ring A2 are as defined herein, are found to be useful in inhibiting metallo-beta-lactamase and therefore in potentiating the activity of beta lactamase antibiotics. The compound can be used alone or in combination with a rhodanine of formula (II) or a pharmaceutically acceptable salt thereof: (II) wherein R.sup.3, Ring A1, n, Ring A2, L and Ring B are as defined herein. Treatment or prevention of bacterial infection in combination with beta-lactam antibiotic agents is also provided.

##STR00001##

A compound which is a thienolate of formula (I) or a pharmaceutically acceptable salt thereof: (I) wherein R.sup.1, R.sup.3, Ring A1, n and Ring A2 are as defined herein, are found to be useful in inhibiting metallo-beta-lactamase and therefore in potentiating the activity of beta lactamase antibiotics. The compound can be used alone or in combination with a rhodanine of formula (II) or a pharmaceutically acceptable salt thereof: (II) wherein R.sup.3, Ring A1, n, Ring A2, L and Ring B are as defined herein. Treatment or prevention of bacterial infection in combination with beta-lactam antibiotic agents is also provided.

##STR00001##

The present invention relates to a compound of Formula (I) or tautomers thereof having pharmacological activity, processes for its preparation, pharmaceutical compositions and their use in the treatment of certain parasitic certain parasitic protozoal infections such as malaria, in particular infection by Plasmodium falciparum.

##STR00001##

(R)-2-((3-(3,5-dichloropyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)-1-(1H-indol-3-yl)propan-1-one

The present invention relates to a compound of Formula (I) or tautomers thereof having pharmacological activity, processes for its preparation, pharmaceutical compositions and their use in the treatment of certain parasitic certain parasitic protozoal infections such as malaria, in particular infection by Plasmodium falciparum.

##STR00001##

(R)-2-((3-(3,5-dichloropyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)-1-(1H-indol-3-yl)propan-1-one

The present invention addresses the problem of providing a therapeutic agent for RNA viral infection that includes a novel combination of a pyrazine derivative and a specific compound, the novel combination exhibiting an effect against the RNA virus. The present invention also addresses the problem of providing a therapeutic agent for RNA viral infection that includes a combination of a pyrazine derivative and a specific compound, the combination being capable of simultaneously enhancing anti-virus activities against multiple RNA viruses. The present invention provides a therapeutic agent for RNA viral infection obtained by combining a pyrazine derivative or a salt thereof and a thiopurine derivative.

This invention explains how to improve and/or extend human life by optimizing metabolic processes. This patent teaches how to reestablish or correct pathways that have been altered either by biochemical stress or by genetic mutation. The body's energetic mitochondrial machinery is programmed for optimization at birth. As events are encountered throughout its lifecycle the cells respond to these stresses by altering their metabolic configurations to meet the immediate demands. Each of these successive adaptive biochemical reactions cumulatively magnifies previous compensatory switches from the original optimal metabolic pathways and diminishes the individual's quality of life and lifespan. As we age these opportunistic adjustments continue to compound and further reduce metabolic efficiency to levels that significantly compromise health and longevity. Modern technology, including molecular biology and micro or nano electronics, is applied to assess the multiple impaired metabolic pathways in an individual and to employ biologic interventions and tools that eliminate those diversions and/or correct genetic and/or epigenetic mutations.

This invention explains how to improve and/or extend human life by optimizing metabolic processes. This patent teaches how to reestablish or correct pathways that have been altered either by biochemical stress or by genetic mutation. The body's energetic mitochondrial machinery is programmed for optimization at birth. As events are encountered throughout its lifecycle the cells respond to these stresses by altering their metabolic configurations to meet the immediate demands. Each of these successive adaptive biochemical reactions cumulatively magnifies previous compensatory switches from the original optimal metabolic pathways and diminishes the individual's quality of life and lifespan. As we age these opportunistic adjustments continue to compound and further reduce metabolic efficiency to levels that significantly compromise health and longevity. Modern technology, including molecular biology and micro or nano electronics, is applied to assess the multiple impaired metabolic pathways in an individual and to employ biologic interventions and tools that eliminate those diversions and/or correct genetic and/or epigenetic mutations.

The present application provides a microsphere in which a main agent is uniformly dispersed in a polymer matrix, wherein an average volume-based particle diameter of the microsphere is 1 μm or more and 150 μm or less, and a variation coefficient of area ratios in four regions is 0.35 or less, wherein the area ratios in four regions are calculated by (s/A)×100 (%) wherein the four regions are prepared by preparing a cross section observation sample obtained by cutting the microsphere; observing the cross section observation sample with an electron microscope at a magnification capable of confirming the main agent in the microsphere or a higher magnification; and dividing the electron microscope observation image into four regions; and A is an area of a respective divided region, and s is a sum of cross section areas of the main agent included in the respective divided region. The microsphere of the present invention can appropriately control the initial release amount of the main agent and its release rate during a subsequent release period, and can continuously release the main agent for a predetermined period of time.

The present application provides a microsphere in which a main agent is uniformly dispersed in a polymer matrix, wherein an average volume-based particle diameter of the microsphere is 1 μm or more and 150 μm or less, and a variation coefficient of area ratios in four regions is 0.35 or less, wherein the area ratios in four regions are calculated by (s/A)×100 (%) wherein the four regions are prepared by preparing a cross section observation sample obtained by cutting the microsphere; observing the cross section observation sample with an electron microscope at a magnification capable of confirming the main agent in the microsphere or a higher magnification; and dividing the electron microscope observation image into four regions; and A is an area of a respective divided region, and s is a sum of cross section areas of the main agent included in the respective divided region. The microsphere of the present invention can appropriately control the initial release amount of the main agent and its release rate during a subsequent release period, and can continuously release the main agent for a predetermined period of time.

Some embodiments of the invention include methods of using a compound such as Formula (I), Formula (II), or I-1 (e.g., in compositions or in pharmaceutical compositions) for treating diseases (e.g., cancer such as chemo-resistant cancer or cancer-therapy-resistant cancer). Additional embodiments of the invention are also discussed herein.