This invention provides novel reagents for cyanating polysaccharides in aqueous or part aqueous solutions so that they may be covalently linked to peptides or proteins either directly or through a spacer. These reagents include 1-cyano-4-dimethylaminopyridinium bromide, or a functional derivative or modification thereof. The examples illustrate the use of these reagents with a variety of polysaccharides and proteins showing that the methods are generally applicable.

Methods and compounds for preventing and arresting COVID-19 morbidity and mortality, via inhibition of Interleukin-6, TNF-alpha, and other cytokines, and via reduction of C-reactive proteins are provided. Analyses of patients with COVID-19 complicated by ARDS, for example, show highly activated cytotoxic T-cells, resulting from hyperactivation of the immune system. A significant surge of Interleukin-6 (IL-6), TNF-α, and other cytokines are thought to be mediators of this enhanced T-cell activity, and runaway inflammation that are dangerous or fatal to the patient. Example oral formulations dubbed BV-4051 and Artovid-20 provide prophylaxis and treatment of these conditions caused by COVID-19 disease. The example formulations contain plant extracts boosting the human immune system and targeting the detrimental effects of the SARS-CoV-2 virus in its various strains.

Methods and compounds for preventing and arresting COVID-19 morbidity and mortality, via inhibition of Interleukin-6, TNF-alpha, and other cytokines, and via reduction of C-reactive proteins are provided. Analyses of patients with COVID-19 complicated by ARDS, for example, show highly activated cytotoxic T-cells, resulting from hyperactivation of the immune system. A significant surge of Interleukin-6 (IL-6), TNF-α, and other cytokines are thought to be mediators of this enhanced T-cell activity, and runaway inflammation that are dangerous or fatal to the patient. Example oral formulations dubbed BV-4051 and Artovid-20 provide prophylaxis and treatment of these conditions caused by COVID-19 disease. The example formulations contain plant extracts boosting the human immune system and targeting the detrimental effects of the SARS-CoV-2 virus in its various strains.

Provided are formulations, methods, and devices for providing a hydrogel. The formulations and resulting hydrogels may be used for treating various disorders, including ocular disorders. In certain embodiments, the hydrogel is formed from formulations comprising (a) a nucleo-functional polymer that is a biocompatible polyalkylene polymer substituted by (i) a plurality of —OH groups, (ii) a plurality of thio-functional groups —R.sup.1—SH wherein R.sup.1 is an ester-containing linker, and (iii) optionally one or more —OC(O)—(C.sub.1-C.sub.6 alkyl) groups, such as a thiolated poly(vinyl alcohol) polymer; (b) an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group, such as a poly(ethylene glycol) polymer containing alpha-beta unsaturated ester groups; and (c) one or more pharmaceutically active agents. In certain embodiments, the hydrogel is formed at a targeted sited using methods and/or devices for focal administration of the formulations and/or hydrogels described herein.

Provided are formulations, methods, and devices for providing a hydrogel. The formulations and resulting hydrogels may be used for treating various disorders, including ocular disorders. In certain embodiments, the hydrogel is formed from formulations comprising (a) a nucleo-functional polymer that is a biocompatible polyalkylene polymer substituted by (i) a plurality of —OH groups, (ii) a plurality of thio-functional groups —R.sup.1—SH wherein R.sup.1 is an ester-containing linker, and (iii) optionally one or more —OC(O)—(C.sub.1-C.sub.6 alkyl) groups, such as a thiolated poly(vinyl alcohol) polymer; (b) an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group, such as a poly(ethylene glycol) polymer containing alpha-beta unsaturated ester groups; and (c) one or more pharmaceutically active agents. In certain embodiments, the hydrogel is formed at a targeted sited using methods and/or devices for focal administration of the formulations and/or hydrogels described herein.

The present disclosure generally relates to improved pharmaceutical compositions useful for the treatment of diseases and disorders. More particularly, the disclosure relates to pharmaceutical compositions comprising glyceryl tribenzoate and/or glyceryl dibenzoate for the treatment of neurodegenerative disorders and peripheral diseases.

The compositions of the present invention comprise at least one medium polarity oil and at least one antibacterial agent, the combination of which produces a synergistic antibacterial effect against bacterial biofilms. Methods are disclosed for the reduction of bacteria in and/or elimination of bacterial biofilms on biological and non-biological surfaces, as well as methods for the treatment of wounds, skin lesions, mucous membrane lesions, and other biological surfaces infected or contaminated with bacterial biofilms.

The compositions of the present invention comprise at least one medium polarity oil and at least one antibacterial agent, the combination of which produces a synergistic antibacterial effect against bacterial biofilms. Methods are disclosed for the reduction of bacteria in and/or elimination of bacterial biofilms on biological and non-biological surfaces, as well as methods for the treatment of wounds, skin lesions, mucous membrane lesions, and other biological surfaces infected or contaminated with bacterial biofilms.

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.