The invention generally relates to solid forms of berberine ursodeoxycholate, and to pharmaceutical compositions, and methods of preparation and therapeutic use thereof. In particular, the invention relates to solid forms of berberine ursodeoxycholate and pharmaceutical compositions thereof useful in treating and/or preventing various diseases or disorders, including metabolic disorders, heart diseases, neurodegenerative diseases and liver diseases.

The present disclosure provides a technique for efficiently detecting a wider variety of RNA higher-order structures including non-Watson-Crick base pair-type higher order structures. The method for analyzing the RNA higher-order structure according to the present disclosure comprises the steps of providing a compound in which a target-binding moiety Sm and an RNA-modifying moiety Y are linked by a linker L; contacting the compound and one or a plurality of RNAs; determining a nucleotide sequence of the RNA after contacting with the compound; and determining a position and/or a region on the RNA that interacts with the target binding moiety of the compound, based on the nucleotide sequence.

The present disclosure provides a technique for efficiently detecting a wider variety of RNA higher-order structures including non-Watson-Crick base pair-type higher order structures. The method for analyzing the RNA higher-order structure according to the present disclosure comprises the steps of providing a compound in which a target-binding moiety Sm and an RNA-modifying moiety Y are linked by a linker L; contacting the compound and one or a plurality of RNAs; determining a nucleotide sequence of the RNA after contacting with the compound; and determining a position and/or a region on the RNA that interacts with the target binding moiety of the compound, based on the nucleotide sequence.

The present disclosure relates to a compound of Formula I or a non-toxic pharmaceutically acceptable salt or solvate thereof, wherein each R1, R2, R3, and R4 is independently selected from methyl (CH.sub.3) and trideuteromethyl (CD.sub.3), at least one of R1, R2, R3, and R4 is selected from trideuteromethyl (CD.sub.3). The compound is a deuterated derivative of L-tetrahydropalmatine, which not only markedly improves pharmacological effects, but also significantly reduces cardiac side effects, liver toxicity, and remarkably decreases individual differences. ##STR00001##

The present disclosure relates to a compound of Formula I or a non-toxic pharmaceutically acceptable salt or solvate thereof, wherein each R1, R2, R3, and R4 is independently selected from methyl (CH.sub.3) and trideuteromethyl (CD.sub.3), at least one of R1, R2, R3, and R4 is selected from trideuteromethyl (CD.sub.3). The compound is a deuterated derivative of L-tetrahydropalmatine, which not only markedly improves pharmacological effects, but also significantly reduces cardiac side effects, liver toxicity, and remarkably decreases individual differences. ##STR00001##

The invention provides novel conjugate compounds having at least one of a moiety derived from ursodeoxycholic acid, or eicosapentaenoic acid, or docosahexaenoic acid, or rhein, or -(+)--lipoic acid, or ursolic acid, or corosolic acid, or hydroxycitric acid, or cinnamic acid, or cholic acid, or oleanolic acid, or salicylic acid, or betulinic acid, or chlorogenic acid, or caffeic acid, or bassic acid, or acetyl L-carnitine, or S-allyl cysteine sulphoxide, or S-methyl cysteine sulfoxide, or pantothenic acid, or ascorbic acid, or retinoic acid, or nicotinic acid, or biotin, or a derivative or analog thereof, and a moiety derived from berberine or L-carnitine or metformin or unsaturated fatty acid, or a derivative or analog thereof. The invention also relates to pharmaceutical compositions, methods of preparation and use of these conjugates in treating and/or preventing, for example, liver diseases or disorders, various diabetes, diabetic complications, dyslipidemia, obesity, metabolic syndromes, pre-diabetes, muscle atrophy, inflammation, and cancers. The compounds of this invention are also useful in improving liver functions in chronic viral associated liver diseases and alcohol-related liver diseases.

The invention provides novel conjugate compounds having at least one of a moiety derived from ursodeoxycholic acid, or eicosapentaenoic acid, or docosahexaenoic acid, or rhein, or -(+)--lipoic acid, or ursolic acid, or corosolic acid, or hydroxycitric acid, or cinnamic acid, or cholic acid, or oleanolic acid, or salicylic acid, or betulinic acid, or chlorogenic acid, or caffeic acid, or bassic acid, or acetyl L-carnitine, or S-allyl cysteine sulphoxide, or S-methyl cysteine sulfoxide, or pantothenic acid, or ascorbic acid, or retinoic acid, or nicotinic acid, or biotin, or a derivative or analog thereof, and a moiety derived from berberine or L-carnitine or metformin or unsaturated fatty acid, or a derivative or analog thereof. The invention also relates to pharmaceutical compositions, methods of preparation and use of these conjugates in treating and/or preventing, for example, liver diseases or disorders, various diabetes, diabetic complications, dyslipidemia, obesity, metabolic syndromes, pre-diabetes, muscle atrophy, inflammation, and cancers. The compounds of this invention are also useful in improving liver functions in chronic viral associated liver diseases and alcohol-related liver diseases.

The present invention provides a mangiferin-6-O-calcium salt and a preparation process thereof. In addition, use of the mangiferin-6-O-calcium salt as defined in claim 1 as an intermediate in the preparation of a mangiferin-6-O-berberine salt is also provided.

The present invention provides a mangiferin-6-O-calcium salt and a preparation process thereof. In addition, use of the mangiferin-6-O-calcium salt as defined in claim 1 as an intermediate in the preparation of a mangiferin-6-O-berberine salt is also provided.

This present application relates to fluorescent tetrazine-containing compounds consisting of a single pi-system. For example, a compound of Formula (I): or a salt thereof, wherein: F is a fluorophore, L is a conjugated linker, and Tz is a substituted or unsubstituted tetrazine; wherein the linker bridges the Tz and F moieties in a single conjugated pi-system. Also provided herein are methods of using the compounds provided herein for biomedical imaging.