Itoham Foods Inc.

Senju Pharmaceutical Co., Ltd.

Kazuhisa Kashimoto

Yumiko Nagano

Yukuo Yoshida

Satomi Onoue

Yoko Minagawa

Akiko Ohata

Atsuko Fujii

Remedies for dry eye and diseases associated with dry eye which contain as the active ingredient peptides represented by the general formula (I):H-His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-X-Gln-X-Ala-Val-X-X-Tyr-Leu-X-X(SEQ ID NOS: 26-36) &#x2003;&#x2003;(I)wherein X, Xand Xrepresent Lys or Arg, respectively; Xrepresents Met, Leu or nLeu; Xrepresents a chemical bond, Asn, Asn-Ser, Asn-Ser-Ile, Asn-Ser-Ile-Leu(SEQ ID NO: 37) or Asn-Ser-Ile-Leu-Asn-X(SEQ ID NOS: 38-43) (wherein Xrepresents a chemical bond, Gly, etc.); and Xrepresents &#x2014;OH or &#x2014;NH, or pharmaceutically acceptable salts thereof:.

Remedies for dry eye and diseases associated with dry eye

This invention relates to a method for producing an LH-RH derivative, characterized in that a peptide fragment shown by general formula (1): pGlu-His-Trp-OR (where R denotes a lower alkyl) and a peptide fragment shown by general formula (2): H-Ser-Tyr-X-Leu-Arg-Pro-Y (where X denotes an amino acid selected from the group consisting of D-amino acids such as D-Leu, D-Ser(But), D-Trp, and (2-napthyl)-D-Ala, and Gly, and Y denotes Gly-NH , Azgly(Azaglycine)-NH or NHR (R is lower alkyl)) are allowed to react in the presence of chymotrypsin or a chymotrypsin-like enzymes, to produce the LH-RH derivative shown by general formula (3): pGlu-His-Trp-Ser-Tyr-X-Leu-Arg-Pro-Y (where X and Y are as defined above). Since the method does not accompany a side reaction such as racemization, it enables simple separation and purification of LH-RH derivatives. Moreover the method enables to provide high yields, as well as recovery and recycling of unreacted peptide fragments, therefore it is valuable in industrial use.

Process for producing LH-RH derivatives

Peptide, a bronchus-expanding agent, and a blood-flow-improving agent

Growing community of inventors

Moriya, Japan

Kazuhisa Kashimoto