This invention provides for synthesis of citrulline from a transition metal complex of ornithine using cyanate to derivatize the terminal amino group of ornithine. The invention also provides improved methods for purification of citrulline produced by reaction of cyanate with ornithine via the steps of reprecipitation of copper complex of citrulline, removal of the complexing metal by sulfide precipitation, activated carbon adsorption and antisolvent crystallization.

The present invention relates to a stabilized pharmaceutical preparation of R27T, the preparation comprising a human interferon beta variant (R27T), an acetate buffer, arginine, trehalose, Poloxamer 188, and methionine. The stabilized R27T pharmaceutical preparation according to the present invention is obtained by the development of a preparation having a novel composition through the substitution of mannitol with trehalose in the composition of a preparation containing mannitol, which was previously studied by the present inventors. It was confirmed that the preparation can remedy a disadvantage of the protein aggregate increase due to the mixing and addition of mannitol and arginine HCl and can improve thermodynamic/structural stability and the resulting stability during the long-term storage, and thus it is expected that the preparation can be advantageously used in the prevention, alleviation, and treatment of multiple sclerosis, cancer, autoimmune diseases, viral infectious diseases, HIV infectious diseases, hepatitis C, rheumatoid arthritis, and the like.

Systems, techniques and methods for estimating the metabolic state or flux, e.g., the body energy state (“BES”) of a patient, are disclosed. The BES provides deep insight into the nutritional needs of the patient, thus allowing for a sort of exquisite glycemic control with regard to the patient. The invention discloses systems and methods for estimating fractional gluconeogenesis, which is the % of glucose production that comes from gluconeogenesis (“GNG”), as opposed to glycogenolysis (“GLY”), the other form of glucose production. Nutritional formulations, materials, cocktails and methods for feeding patients by parenteral and other means are disclosed. The amount, type and rate of such nutritional feeding are typically based upon the above estimating. The invention discloses formulations that contain labels, such as deuterium, for medical diagnostics, such as for estimating BES and fractional gluconeogenesis. The invention is suitable for any sort of patient, including those who are injured, such as with traumatic brain injury, ill, or have other conditions that stress the metabolic system.

Provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) a homing receptor, ii) Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Further provided herein are modified NK-92® cells comprising one or more nucleic acids encoding i) IL-12 and/or TGF-beta trap, ii) an Antigen Binding Protein (ABP) or Chimeric Antigen Recpetor (CAR) that specifically binds to a target antigen, iii) an Fc Receptor such as CD16 or CD16-158V, and/or iv) a cytokine, wherein the nucleic acid sequence is operably linked to a promoter. Also provided are compositions and kits comprising the modified NK-92® cells, as well as methods of treating cancer using the modified cells.

The invention provides liquid injectable copolymers of TMC and HTMC that are degradable in vivo. Degradation can be tailored by adjusting the amount of HTMC in the copolymer, the initial molecular weight of the copolymer, and the characteristics of the initiator used in its preparation. Specifically, the degradation rate increases as the amount of HTMC incorporated into the copolymer increases, as the molecular weight of the copolymer decreases, and as the hydrophobicity of the initiator decreases. Moreover, the degradation yields products such as glycerol and carbon dioxide that are non-toxic in vivo, and which will not cause a substantive change in tissue pH upon implantation in vivo. The copolymers may be used in applications such as drug delivery and as coatings.

The present disclosure relates to parenteral nutrition formulations, including ready-to-use parenteral nutrition formulations which are reconstituted from multi-chamber containers and amino acid formulations. More particularly, the present disclosure is directed to formulations comprising butyrate derivatives, specifically arginine butyrate, for use with adult or pediatric patients. The disclosure further provides for methods of reducing or preventing systemic and local inflammation of patients receiving parenteral nutrition, and methods of maintaining or ameliorating their systemic immunity and local immunity, as well as the patients' gut barrier functions.

The invention provides carbazole derivatives for the treatment of fibrotic diseases (pathological collagen deposition) in tissues and organs, and related symptoms, and conditions thereof.

The present invention provides methods of use of hexokinase 2 (HK2)/mitochondria-detaching compounds, including jasmonate derivatives and piperazine derivatives and pharmaceutical compositions including such compounds for inducing immune responses in a subject, including potentiating the immune response to hyperproliferative disorders such as cancer and potentiating the immune response to infectious diseases.

The present invention relates to pharmaceutical compositions suitable for parenteral administration in human subjects. In particular, the present invention relates to isotonic pharmaceutical compositions for parenteral administration.

Disclosed are crystalline salts of Compound I, methods of preparing them, and related pharmaceutical preparations thereof. Also disclosed are methods of treatment using the crystalline salts of the invention.

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