The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as IRAK inhibitors.

An object of the present invention is to provide immunogenic compositions for protection against S. pneumoniae, in particular against S. pneumoniae serogroup 9, while limiting the number of conjugates. The present invention thereforerelates to new immunogenic compositions for use in pneumococcal vaccines and to vaccination of human subjects, in particular infants and elderly, against pneumoccocal infections using said immunogenic compositions.

The present disclosure provides compounds that include a tetrazolone derivative of a carboxyl group of an active agent. This disclosure also relates to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, and processes for preparing these compounds.

The invention relates to an oil-in-water dispersion comprising coniferous resin acids, its preparation and use as an antimicrobial and anti-inflammatory agent in medical and non-medical products. The invention also relates to a pharmaceutical product comprising the oil-in-water dispersion.

In one aspect, the invention relates to a composition including a first polypeptide having the sequence set forth in SEQ ID NO: 1 and a second polypeptide having the sequence set forth in SEQ ID NO: 2. In one embodiment, the composition includes about 120 μg/ml of a first polypeptide including the amino acid sequence set forth in SEQ ID NO: 1, 120 μg/ml of a second polypeptide including the amino acid sequence set forth in SEQ ID NO: 2, about 2.8 molar ratio polysorbate-80 to the first polypeptide, about 2.8 molar ratio polysorbate-80 to the second polypeptide, about 0.5 mg/ml aluminum, about 10 mM histidine, and about 150 mM sodium chloride. In one embodiment, a dose of the composition is about 0.5 ml in total volume. In one embodiment, two-doses of the composition induce a bactericidal titer against diverse heterologous subfamily A and subfamily B strains in a human.

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.

Stable pharmaceutical compositions comprising a compound of Formula (I) or a stereoisomer or a pharmaceutically acceptable derivative thereof are disclosed. Formula (I)

##STR00001##

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.

Our invention is a mixture of carboxylic acids: citric acid, succinic acid, fumaric acid and malic acid, and any possible combinations thereof. This product is used orally or also intravenously, in the treatment of patients with chronic renal failure, hyperammonemia or human conditions having negative nitrogen balance. This product is beneficial in decreasing the serum values of urea and serum ammonium, while promoting by transamination of the oxalacetate formed via succinate, fumarate and malate, the biosynthesis of non-essential amino acids; by transamination of the alpha ketoglutarate formed via citrate, it generates glutamic acid and related amino acids such as glutamine. This treatment prevents, preserves and even improves kidney function. In other patients it delays deterioration of renal function and the urgent need for renal replacement therapy. In others, it is used as a supplemental renal replacement treatment to improve the patient's quality of life and improve laboratory parameters.

The invention features probiotic bacteria expressing Clostridium difficile SlpA, or fragment thereof, and its use for the treatment or prevention of Clostridium difficile infection and gut colonization.