This invention relates to antisense oligonucleotides comprising at least one N3′.fwdarw.P5′ phosphorodiamidate linkage (NPN) in the backbone as well as methods for using the same. The antisense oligonucleotides can effectively prevent or decrease protein expression.

The present invention provides methoxy-substituted pyrrolopyridines, pharmaceutical compositions thereof, methods of modulating RORγ activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such pyrrolopyridines and pharmaceutical compositions thereof.

The dual microbial preparation contains the microscopic oomycete Pythium oligandrum and components of a physiological microbiome. The microscopic oomycete Pythium oligandrum and the physiological microbiome component are present in the dual preparation in a form which facilitates their germination, subsequent propagation and colonization of the target tissues. The microscopic oomycete Pythium oligandrum is incorporated in a quantity of 10.sup.3 to 10.sup.7 CFU (colony forming units), with 10.sup.4 to 10.sup.5 CFU per one cycle of application preferably. The physiological microbiome component contains 5×10.sup.6 to 5×10.sup.10 CFU, with 5×10.sup.7 to 5×10.sup.9 per one cycle of application preferably. The fermented substrate found in the Pythium oligandrum oomycete is the source of nutrients for both microbial components. The dual microbial preparation also contains at least one auxiliary substance from a group including a desiccant, components of a buffer system, an anti-caking substance and an agent for the creation of a physiological osmotic environment. The physiological microbiome component is a component of the human microbiome, one of the microbes of the green complex, such as the Capnocytophaga sputigena bacterium, or one of the components of the healthy skin microbiome, such as the Staphyloccocus epidermidis bacterium, or one of the components of the healthy vaginal microbiome, such as the peroxide producing Lactobacillus crispatus. Either the microscopic oomycete Pythium oligandrum or the physiological microbiome component is present in the dual microbial preparation in the form of inactivated cells, cell extracts or isolated cell fractionation. The microbial activator for the Pythium oligandrum oomycete is a yeast autolysate in a quantity of 0.1% to 10% weight of the total quantity of dual microbial preparation. The auxiliary substances are regulated in a way which allows for application in the form of an ointment, cream, oil or suppository or in the form of a liquid aqueous preparation.

There are described RORγ modulators of the formula (I),

##STR00001##

and formula (II)

##STR00002##

or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

Provided herein are intermediates and processes useful for facile synthesis of compounds of formula (I):

##STR00001##

or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein Q, P.sup.1 and P.sup.2 are as defined in this disclosure.

Provided herein are substituted imidazo[1,2-a]pyridin-2-ylamine compounds, for example, of formula (A), and pharmaceutical compositions thereof; and methods of their use for treating, preventing, or ameliorating one or more symptoms of a Janus kinase-mediated disease.

##STR00001##

Combinations of a muscarinic acetylcholine receptor antagonist and a beta 2 agonist for inhaled administration via the nose or mouth, and methods of using them are provided.

Compounds of formula I and their metabolites are potent mediators of an inflammatory response:

##STR00001##

where a, b, c, d, e, f, V, W, X, Y, R.sup.a, R.sup.a′, R.sup.b, R.sup.b′, R.sup.c, and R.sup.c′ are defined herein. In particular, the compounds of the invention are candidate therapeutics for treating inflammatory conditions.

The subject invention relates to novel micoparticulate and soluble forms of flavonoids, and their synthesis. The invention also includes novel formulations of such flavonoids. Further, the invention includes novel methods of manufacturing the flavonoid formulations. The invention also relates to a wide variety of applications of the flavonoid formulations.

The invention describes a method and compounds for the prevention of immune responses towards allofactors, towards viral vectors used for gene therapy and gene vaccination, towards proteins to which subjects are naturally exposed, towards genetically-modified organisms and towards undesirable effects related to vaccine administration for allergic or infectious diseases.