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 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 R-(+)--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 various novel compositions of berberine in combination with pharmacologically active organic acids, and related methods of their use in treating various diseases or disorders. The invention further provides various novel compounds prepared from berberine and pharmacologically active organic acids and prepared from ursodeoxycholic acid and pharmacologically active organic bases, and pharmaceutical compositions thereof, and methods of their preparation and therapeutic use in treating and/or preventing various diseases or disorders. The compounds and pharmaceutical compositions of the invention can be utilized to treat various diseases or disorders, such as diabetes, diabetic complications, dyslipidemia, hyperlipidemia, obesity, metabolic syndromes, pre-diabetes, atherosclerosis, heart diseases, neurodegenerative diseases, sarcopenia, muscle atrophy, inflammation, cancer and liver diseases and conditions such as fatty liver, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cholestatic liver diseases or graft-versus-host disease of the liver. 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 various novel compositions of berberine in combination with pharmacologically active organic acids, and related methods of their use in treating various diseases or disorders. The invention further provides various novel compounds prepared from berberine and pharmacologically active organic acids and prepared from ursodeoxycholic acid and pharmacologically active organic bases, and pharmaceutical compositions thereof, and methods of their preparation and therapeutic use in treating and/or preventing various diseases or disorders. The compounds and pharmaceutical compositions of the invention can be utilized to treat various diseases or disorders, such as diabetes, diabetic complications, dyslipidemia, hyperlipidemia, obesity, metabolic syndromes, pre-diabetes, atherosclerosis, heart diseases, neurodegenerative diseases, sarcopenia, muscle atrophy, inflammation, cancer and liver diseases and conditions such as fatty liver, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cholestatic liver diseases or graft-versus-host disease of the liver. 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 processes for the synthesis of substituted berbine compounds. Also provided are intermediates used in the synthesis of substituted berbine compounds.

The present invention provides processes for the synthesis of substituted berbine compounds. Also provided are intermediates used in the synthesis of substituted berbine compounds.

The present invention relates to a diarylo[a,g]quinolizidine compound of formula (I), enantiomer, diastereoisomer, racemate, mixture, pharmaceutically acceptable salt, crystalline hydrate or solvate thereof; the preparation method thereof, and uses thereof in preparing an experimental model drugs related to dopamine receptors and 5-HT receptors or a medicament for treating or preventing a disease related to dopamine receptors and 5-HT receptors. ##STR00001##

The present invention relates to a diarylo[a,g]quinolizidine compound of formula (I), enantiomer, diastereoisomer, racemate, mixture, pharmaceutically acceptable salt, crystalline hydrate or solvate thereof; the preparation method thereof, and uses thereof in preparing an experimental model drugs related to dopamine receptors and 5-HT receptors or a medicament for treating or preventing a disease related to dopamine receptors and 5-HT receptors. ##STR00001##

The present invention is a method and compound for treating specific cancerous cell lines. The invention treats liver cancer by directing a cancer-fighting drug into the liver hepatoportal circuit. The cancer-fighting drug is attached to a naturally produced molecule which functions primarily in the hepatoportal circuit and has organotropism for the hepatoportal circuit.

The present invention relates to small molecule compounds and their use as HDAC inhibitors and in the treatment of various diseases, such as cancer. The present invention further relates to methods of synthesizing the compounds and methods of treatment. H-L(HA), H is a head group selected from (head group 1), (head group 2), (head group 3), (head group 4), (head group 5) and (head group 6).

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