The present invention relates to lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS) or derivatives thereof for use in the treatment of atherosclerotic cardiovascular disease, and further provides particular such lyso-DGTS derivatives.

The present invention relates to lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS) or derivatives thereof for use in the treatment of atherosclerotic cardiovascular disease, and further provides particular such lyso-DGTS derivatives.

The present application relates to a cell cryopreservation protective composition, the use of the composition, and a cell cryopreservation method. The cell cryopreservation protective composition comprises a zwitterionic molecule having the general formula R.sub.1—N.sup.+(CH.sub.3).sub.2—(CH.sub.2).sub.n—R.sub.2, wherein R.sub.1 is a linear or branched alkyl having 1 to 10 carbon atoms, and is optionally substituted with a substituent; R.sub.2 is any negatively charged group selected from the group consisting of —COO.sup.−, —SO.sub.4.sup.−, —SO.sub.3.sup.−, and (I); and R.sub.3 is a group selected from the group consisting of (methyl)acryloyloxyalkyl, alkyl and alkenyl; and the zwitterionic molecule having general formula R.sub.1—N.sup.+(CH.sub.3).sub.2—(CH.sub.2).sub.n—R.sub.2 is preferably a betaine compound. The cell cryopreservation protective composition can carry out cell cryopreservation in a non-toxic and efficient manner, and results in an extremely high post-thaw cell survival rate and does not require stepwise cryopreservation. After cell recovery, the cells can be used directly or after being slightly diluted. ##STR00001##

The present application relates to a cell cryopreservation protective composition, the use of the composition, and a cell cryopreservation method. The cell cryopreservation protective composition comprises a zwitterionic molecule having the general formula R.sub.1—N.sup.+(CH.sub.3).sub.2—(CH.sub.2).sub.n—R.sub.2, wherein R.sub.1 is a linear or branched alkyl having 1 to 10 carbon atoms, and is optionally substituted with a substituent; R.sub.2 is any negatively charged group selected from the group consisting of —COO.sup.−, —SO.sub.4.sup.−, —SO.sub.3.sup.−, and (I); and R.sub.3 is a group selected from the group consisting of (methyl)acryloyloxyalkyl, alkyl and alkenyl; and the zwitterionic molecule having general formula R.sub.1—N.sup.+(CH.sub.3).sub.2—(CH.sub.2).sub.n—R.sub.2 is preferably a betaine compound. The cell cryopreservation protective composition can carry out cell cryopreservation in a non-toxic and efficient manner, and results in an extremely high post-thaw cell survival rate and does not require stepwise cryopreservation. After cell recovery, the cells can be used directly or after being slightly diluted. ##STR00001##

A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment.

A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment.

It has been found that the membrane permeability of peptide compounds can be improved by making at least one of amino acids constituting the peptide compound be an amino acid having a side chain capable of forming an intramolecular hydrogen bond.

It has been found that the membrane permeability of peptide compounds can be improved by making at least one of amino acids constituting the peptide compound be an amino acid having a side chain capable of forming an intramolecular hydrogen bond.

Compounds are provided that are useful as immunomodulators. The compounds have the Formula (I) ##STR00001##
including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1a, R.sup.1b, R.sup.1c, R.sup.1d, R.sup.2a, R.sup.2b, R.sup.3, R.sup.3a, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and the subscript n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Methods for making a dolastatin, auristatin or related compounds comprising the steps of providing a universal dolastatin core of Formula (I) reacting the C-terminal carboxylic acid group with an amine (A) to form an amide bond and reacting the N-terminal amine with a carboxylic acid (CA) to form an amide bond, wherein the steps can be performed in either order. Also provided are an isolated salt of the universal dolastatin core for use in preparation of dolastatins, auristatins and related compounds. Also provided are a number of intermediates and process steps which are useful for the preparation of high purity dolastatin core and high purity dolastatin and auristatin compounds.