The disclosed subject matter provides certain polymorphic forms of Compound (I) as well as pharmaceutical compositions comprising Compound (I) or such polymorphic forms, and methods of using or making such compounds and pharmaceutical compositions. It has now been discovered that Compound (I) can exist in multiple crystalline forms (polymorphs). One particular crystalline form, Form II, has been found to be more thermodynamically stable and, thus, likely more suitable for bulk preparation and handling than other polymorphic forms. Efficient and economic methods have been developed to prepare Compound (I) and Form II in high purity on a large scale. In animal studies, Form II has demonstrated safety and efficacy in treating depressive disorders and, when micronized, improved absorption compared to non-micronized Form II. ##STR00001##

The present invention is directed to antibodies and antigen binding fragments thereof having binding specificity for PACAP. The antibodies and antigen binding fragments thereof comprise the sequences of the V.sub.H, V.sub.L, and CDR polypeptides described herein, and the polynucleotides encoding them. Antibodies and antigen binding fragments described herein bind to and/or compete for binding to the same linear or conformational epitope(s) on human PACAP as an anti-PACAP antibody. The invention contemplates conjugates of anti-PACAP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. Methods of making said anti-PACAP antibodies and antigen binding fragments thereof are also contemplated. Other embodiments of the invention contemplate using anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, photophobia, mast cell degranulation, and/or neuronal activation, would be therapeutically beneficial.

The present invention relates to a composition including plant extracts. The composition according to the present invention has a blood circulation improvement effect by restoring nitric oxide (NO) reduced by oxLDL, has a cholesterol improvement effect by inhibiting cholesterol synthesis, has an anti-obesity effect by promoting breakdown of triglycerides, has an immune function improvement effect by increasing interferon gamma, has a female menopause improvement effect by activating estrogen signaling, has an anti-allergic effect by inhibiting IgE that causes allergies, has a blood glucose control effect by promoting intracellular glucose uptake, has a cognitive function improvement effect by inhibiting beta-secretase activity, has a liver health improvement effect by restoring liver cell viability decreased by alcohol (ethanol) treatment, and has an andropause improvement effect by activating androgen signaling. Due to these characteristics, the composition may be used as a pharmaceutical, food, or health functional food composition.

The present invention relates to a composition including plant extracts. The composition according to the present invention has a blood circulation improvement effect by restoring nitric oxide (NO) reduced by oxLDL, has a cholesterol improvement effect by inhibiting cholesterol synthesis, has an anti-obesity effect by promoting breakdown of triglycerides, has an immune function improvement effect by increasing interferon gamma, has a female menopause improvement effect by activating estrogen signaling, has an anti-allergic effect by inhibiting IgE that causes allergies, has a blood glucose control effect by promoting intracellular glucose uptake, has a cognitive function improvement effect by inhibiting beta-secretase activity, has a liver health improvement effect by restoring liver cell viability decreased by alcohol (ethanol) treatment, and has an andropause improvement effect by activating androgen signaling. Due to these characteristics, the composition may be used as a pharmaceutical, food, or health functional food composition.

A pharmaceutical mucoadhesive gel composition for delivering therapeutic agents (such as progesterone) by buccal, nasal, vaginal and rectal administration, thereby avoiding the hepatic first-pass metabolism. The gel composition comprises a vehicle with a gel-forming agent and a bioadhesive agent; and a therapeutic agent dispersed or suspended in the vehicle.

It is provided a pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one, at least one sterol or an ester thereof and a mixture of acylglycerols with a solid fat content of less than 25% at 25° C. and 0% at 37° C. In addition it is provided a method for preparing the pharmaceutical composition.

The present disclosure provides compositions and methods for treating estrogen-dependent disorders, such as disorders of the female reproductive system, including uterine fibroids and endometriosis, among others. Compounds described herein that may be used to treat such indications include gonadotropin-releasing hormone (GnRH) antagonists. Suitable GnRH antagonists useful in conjunction with the compositions and methods described herein include thieno[3,4d]pyrimidine derivatives, such as 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno [3,4d]pyrimidine-5-carboxylic acid and the choline salt thereof, among others. Using the compositions and methods described herein, GnRH antagonists may be periodically administered to a patient, such as one or more times per day, week, or month, in combination with periodic add-back therapy, thereby preventing bone mineral density loss that may otherwise accompany estrogen depletion effectuated by GnRH antagonist activity. Advantageously, using the dosing schedules of the present disclosure, the periodic administration the GnRH antagonist and add-back therapy may commence together, such as on the same day.

Compounds are provided herein that antagonize corticotropin-releasing factor (CRF) receptors, in particular CRF receptor 1 (CRF.sub.1), as well as related preparations, compositions and methods for treating diseases and/or disorders that would benefit from the same such as congenital adrenal hyperplasia (CAH).

##STR00001##

The present invention relates to monolithic intravaginal rings comprising progesterone, methods of making, and uses thereof. The intravaginal rings comprise progesterone, a polysiloxane elastomer, and a pharmaceutically acceptable hydrocarbon or glycerol esters of a fatty acid.

Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity.