The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, the treatment of ischemic injury, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, infections of the skin, peripheral vascular disease, stroke, asthma, and the like.

Disclosed herein are compounds of formula (I)

##STR00001##

and therapeutic methods of treatment with compounds of formula (I), wherein L.sup.1, L.sup.2, L.sup.4, R.sup.1, R.sup.4, R.sup.5, R.sup.6, and s are as defined in the specification. Compounds of formula (I) are EP4 agonists useful in the treatment of glaucoma, neuropathic pain, and related disorders.

An object of the present invention is to provide an effective and safe medicament having effects for mitigating conditions and/or suppressing onset of a peripheral neuropathy induced by administration of an anti-malignant tumor agent, oxaliplatin, in a human cancer patient receiving an anti-malignant tumor treatment with oxaliplatin. There is provided a medicament for mitigating conditions and/or suppressing onset of a peripheral neuropathy induced by oxaliplatin in an anti-malignant tumor treatment consisting of repetition of a single cycle comprising intravenous administration of oxaliplatin to a human cancer patient and following drug withdrawal, which contains thrombomodulin for intravenously administering 0.06 mg/kg of thrombomodulin once per said single cycle of the treatment on the first day of each said cycle as an active ingredient.

An object of the present invention is to provide an effective and safe medicament having effects for mitigating conditions and/or suppressing onset of a peripheral neuropathy induced by administration of an anti-malignant tumor agent, oxaliplatin, in a human cancer patient receiving an anti-malignant tumor treatment with oxaliplatin. There is provided a medicament for mitigating conditions and/or suppressing onset of a peripheral neuropathy induced by oxaliplatin in an anti-malignant tumor treatment consisting of repetition of a single cycle comprising intravenous administration of oxaliplatin to a human cancer patient and following drug withdrawal, which contains thrombomodulin for intravenously administering 0.06 mg/kg of thrombomodulin once per said single cycle of the treatment on the first day of each said cycle as an active ingredient.

This invention relates to a method for generating, repairing and/or maintaining connective tissue in a subject. In one embodiment, the invention relates to a method for generating, repairing and/or maintaining cartilage tissue in a subject. The present invention also relates to a method of treating and/or preventing a disease in a subject arising from degradation and inflammation of connective tissue.

Disclosed herein are neural extracellular vesicles (EVs) and methods of using these EVs in the treatment of spinal cord injury, stroke, and traumatic brain injury and neurodegenerative disease.

The purpose of the present invention is to provide an aqueous patch in which basic physical properties as an aqueous patch are less likely to deteriorate and crystals of 1-menthol are less likely to precipitate. The aqueous patch includes, in a pasty preparation, 1-menthol: 0.5% by mass or more and 10% by mass or less, an oil component: 0.2% by mass or more and 19% by mass or less; and silica: 0.1% by mass or more and 5.5% by mass or less.

Disclosed herein are methods and compositions for treating or preventing neuropathic pain in a subject, the method comprising administering to a subject a therapeutically effective amount of prolactin, or a functional variant thereof, wherein the functional variant comprises a peptide of formula (I) or a pharmaceutically acceptable salt thereof: R.sup.1-C-R-I-X.sub.1-X.sub.2-X.sub.3-X.sub.4-N-C-R.sup.2 (I) (SEQ ID NO:1) wherein X.sub.1 is an amino acid residue selected from isoleucine (I) and valine (V); X.sub.2 is an amino acid residue selected from histidine (H) and tyrosine (Y); X.sub.3 is an amino acid residue selected from aspartic acid (D) and asparagine (N); X.sub.4 is an amino acid Nresidue selected from asparagine (N) and serine (S); R.sup.1 is selected from the group consisting of YLKLLK, LKLLK, KLLK, LLK, LL, K or R.sup.1 is absent; and R.sup.2 is G (glycine), or R.sup.2 is absent.

Disclosed herein are methods and compositions for treating or preventing neuropathic pain in a subject, the method comprising administering to a subject a therapeutically effective amount of prolactin, or a functional variant thereof, wherein the functional variant comprises a peptide of formula (I) or a pharmaceutically acceptable salt thereof: R.sup.1-C-R-I-X.sub.1-X.sub.2-X.sub.3-X.sub.4-N-C-R.sup.2 (I) (SEQ ID NO:1) wherein X.sub.1 is an amino acid residue selected from isoleucine (I) and valine (V); X.sub.2 is an amino acid residue selected from histidine (H) and tyrosine (Y); X.sub.3 is an amino acid residue selected from aspartic acid (D) and asparagine (N); X.sub.4 is an amino acid Nresidue selected from asparagine (N) and serine (S); R.sup.1 is selected from the group consisting of YLKLLK, LKLLK, KLLK, LLK, LL, K or R.sup.1 is absent; and R.sup.2 is G (glycine), or R.sup.2 is absent.

This document relates to methods and materials for treating a mammal having neurotoxicity (e.g., chemotherapy-induced neurotoxicity). For example, one or more T-type calcium channel modulators (e.g., a composition including one or more T-type calcium channel modulators such as CX-8998) can be administered to a mammal having neurotoxicity to treat the mammal.