EP0090798A1 - Medicament a base d'un antagoniste de la substance p - Google Patents

Medicament a base d'un antagoniste de la substance p

Info

Publication number
EP0090798A1
EP0090798A1 EP81902811A EP81902811A EP0090798A1 EP 0090798 A1 EP0090798 A1 EP 0090798A1 EP 81902811 A EP81902811 A EP 81902811A EP 81902811 A EP81902811 A EP 81902811A EP 0090798 A1 EP0090798 A1 EP 0090798A1
Authority
EP
European Patent Office
Prior art keywords
substance
trp
pro
prophylactically
antagonist
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP81902811A
Other languages
German (de)
English (en)
Inventor
Rolf Hakanson
Joachim HÖRIG
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ferring AB
Original Assignee
Ferring AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ferring AB filed Critical Ferring AB
Publication of EP0090798A1 publication Critical patent/EP0090798A1/fr
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids

Definitions

  • the present invention relates to a Substance P antagonist for use in drugs for the prophylactic or therapeutic treatment of diseases released by Substance P, to a method of prophylactically or therapeutically treat ing such a disease, and to a drug for prophylactically. or therapeutically treating inflammations. More specifically, the invention relates to a Substance P antagonist which, in relation to Substance P, has a structure in which L-proline in position 2 has been replaced by D-proline, and L-phenylalanine in position 7 and
  • the Substance P antagonist according to this inven tion thus is (D-Pro 2 , D-Trp 7 ' 9 ) Substance P having the formula
  • transmitter substances or transmitters consist not only of substances related to adrenaline and acetyl choline (adrenergic and cholinergic nerves, respectively), but also of chemical compounds made up of a series of amino acids joined by peptide bonds, i.e. polypeptides or oligopeptides. In most cases, peptides alone can serve as such neur ⁇ transmitters. A whole series of peptides having this function are already known (see for example the papers published in the New England Journal of Medicine, Vol. 304, pp. 876-885 and 944-951).
  • Substance P may be classed among transmitter substances because it has been shown to occur both in nerves transmitting impulses from peripheral parts of the body to the brain (afferents) and nerves extending from the brain (or peripheral ganglia) to different peripheral organs (efferents).
  • Substance P is deemed to play an important part in the transmission of pain stimuli from the periphery to the brain.
  • the efferent nerves which contain Substance P are apparently capable of stimulating secretion from endocrine glands and causing vasodilation and. contraction of smooth muscle.
  • Substance P as synthetized by us has an inhibiting effect on inflammatory conditions in the body, especially the skin, the upper airpassages, the intestine and the eye.
  • the present invention therefore relates to the Substance P antagonist (D-Pro 2 , D-Trp 7,9 ) Substance P for use in drugs for the prophylactic or therapeutic treatment of diseases released by substance P.
  • the invention concerns a drug for the prophylactic or therapeutic treatment of inflammations, in particular inflammations in the eye.
  • the invention relates to a method of prophylatically or therapeutically treating diseases released by Substance P, in particular such diseases as inflammations in the skin, the upper air-passages, the intestine and/or the eye.
  • a suitable form for administration of the drug according to this invention is by topical application. Preparation of the Substance P antagonist according to the invention
  • L-Arg-D-Pro-L-Lys-L-Pro-L-Gln-L-Gln-D-Trp-L-Phe-D-Trp-L-Leu-L-Met-NH 2 is prepared in a manner that is conventional in this particular field, viz. by the solid phase method described by R.B. Merrifield (J. Am. Chem. Soc., 85, (1963), 2149-2154).
  • the solid phase employed is the benzhydrylamine resin described by Monahan et al. (Biochem. Biophys. Res. Com. 48, 1100-1105, (1972)).
  • the starting materials employed in the preparation were Boc-Arg-Tos, Boc-Gln-ONp and Boc-Leu from Ferring AB, Malmö, Sweden; D-Pro, Pro, D-Trp and Phe from Merck Darmstadt, Federal Republic of Germany; and the benzhydrylamine resin from Beckman Inc.
  • the synthesis was conducted by stages, starting from 5 g BHA resin, 0.51 meq. NH 2 /g, and the amino acids in the compound according to the invention were coupled according to the following schedule
  • the peptide content of the material was 86.7%, based on the triacetate.
  • the Substance P antagonist used for the present invention was shown to inhibit or cure inflammation by the following experiment.
  • a similar inflammatory reaction can be evoked by infrared radiation of a restricted area on the iris.
  • the Substance P antagonist according to this invention 90 nmol of the Substance P antagonist according to this invention were injected into the corpus vitrium of the left eye (3 rabbits).
  • the right eye was used for control purposes and was given 0.9% saline.
  • the irises of both eyes were exposed to infrared radiation.
  • the amount of protein in the chamber fluid was measured, and it was found that the so-called light path in the left, treated eye was substantially unchanged, whereas it had been trebled in the right control eye.
  • the experiments carried out to induce inflammation by infrared radiation also comprised experiments which showed that the minimum amount of recordable effects was 0.9 nmol of the Substance P antagonist in saline, while the minimum dose for maximum effect was 90 nmol in saline.
  • the effect of the antagonist was found to be dose-dependent and rather linear.
  • the Substance P antagonist according to the invention was used dissolved in saline for injection and eye drops, but other forms of administration for topical application by spraying, inhalation, instillation, insufflation and injection are also possible. Furthermore, salves, creams, suppositories, tablets, capsules and granulates can be prepared in which the active constituent consists of the Substance P antagonist according to this invention and the remaining ingredients are conventional inert carriers, diluents, excipients etc.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Un antagoniste de substance P est utilisé dans des médicaments pour le traitement prophylactique ou thérapeutique de maladies déclenchées par la substance P. L'antagoniste consiste en (D-Pro2, D-Trp7,9) Substance P ayant la formule$(6,)$. Un médicament pour le traitement prophylactique ou thérapeutique d'inflammations, spécialement dans l'oeil, est également décrit, ce médicament contenant comme substance active l'antagoniste de la substance P mentionné ci-dessus. De plus, un procédé de traitement prophylactique ou thérapeutique d'une maladie déclenchée par la substance P, ou des inflammations, spécialement dans l'oeil, est également décrit. Dans ce procédé, on utilise une quantité thérapeutiquement active de (D-Pro2, B-Trp7,9) Substance P, spécialement sous une forme appropriée à une application locale.
EP81902811A 1981-10-09 1981-10-09 Medicament a base d'un antagoniste de la substance p Ceased EP0090798A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/SE1981/000292 WO1983001252A1 (fr) 1981-10-09 1981-10-09 Medicament a base d'un antagoniste de la substance p

Publications (1)

Publication Number Publication Date
EP0090798A1 true EP0090798A1 (fr) 1983-10-12

Family

ID=20342922

Family Applications (1)

Application Number Title Priority Date Filing Date
EP81902811A Ceased EP0090798A1 (fr) 1981-10-09 1981-10-09 Medicament a base d'un antagoniste de la substance p

Country Status (5)

Country Link
EP (1) EP0090798A1 (fr)
JP (1) JPS58501675A (fr)
BE (1) BE894602A (fr)
IT (1) IT1191028B (fr)
WO (1) WO1983001252A1 (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989001772A1 (fr) * 1987-09-03 1989-03-09 University Of Georgia Research Foundation, Inc. Composition de cyclosporine oculaire
US6203803B1 (en) 1994-12-14 2001-03-20 Societe L'oreal S.A. Use of a substance P antagonist in a cosmetic composition, and the composition thus obtained
FR2719474B1 (fr) * 1994-05-05 1996-05-31 Oreal Utilisation d'un antagoniste de substance P dans une composition cosmétique et composition obtenue.
FR2719476B1 (fr) * 1994-05-05 1997-05-23 Oreal Utilisation d'un antagoniste de substance P dans une composition cosmétique et composition obtenue.
FR2728265A1 (fr) * 1994-12-19 1996-06-21 Oreal Utilisation d'un antagoniste de substance p dans une composition pharmaceutique
FR2732598B1 (fr) 1995-04-10 1997-05-09 Oreal Utilisation de sel de metaux alcalino-terreux pour le traitement des prurits et des dysesthesies oculaires ou palpebraux
EP0737471A3 (fr) * 1995-04-10 2000-12-06 L'oreal Utilisation d'un sel d'une métal alcalino-terreux comme inhibiteur de TNF-alpha dans une composition unique et composition obtenue
FR2737408B1 (fr) * 1995-07-31 1997-09-05 Oreal Utilisation d'un antagoniste de bradykinine dans une composition cosmetique, pharmaceutique ou dermatologique et composition obtenue
FR2738741B1 (fr) * 1995-09-19 1997-12-05 Oreal Composition pour la teinture des fibres keratiniques, contenant un antagoniste de substance p
FR2740335B1 (fr) * 1995-10-26 1997-12-19 Oreal Utilisation de sel de lanthanide, de lithium, d'etain, de zinc, de manganese ou d'yttrium comme antagoniste de substance p
FR2740341B1 (fr) * 1995-10-26 1997-12-19 Oreal Utilisation de sel de lanthanide, d'etain, de zinc, de manganese, d'yttrium, de cobalt, de baryum, de strontium dans une composition pour la peau

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3954640A (en) * 1973-06-27 1976-05-04 Xerox Corporation Electrostatic printing inks
US4052325A (en) * 1974-12-23 1977-10-04 Eastman Kodak Company Liquid electrographic developer composition containing redispersible polyester toner and process
JPS5425833A (en) * 1977-07-29 1979-02-27 Canon Inc Electrophotography
US4202785A (en) * 1978-05-15 1980-05-13 Eastman Kodak Company Polyesterionomers having utility in liquid electrographic developer compositions
JPS5725832A (en) * 1980-07-23 1982-02-10 Olympus Optical Co Light source apparatus for endoscope

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8301252A1 *

Also Published As

Publication number Publication date
BE894602A (fr) 1983-01-31
IT8223678A1 (it) 1984-04-08
JPS58501675A (ja) 1983-10-06
IT8223678A0 (it) 1982-10-08
WO1983001252A1 (fr) 1983-04-14
IT1191028B (it) 1988-02-24

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Legal Events

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Inventor name: HAKANSON, ROLF

Inventor name: HOERIG, JOACHIM