Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
  • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
  • A61K38/046—Tachykinins, e.g. eledoisins, substance P; Related peptides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• the invention relates to the field of wound healing.
• it relates to treatment of wounds inflicted by disease, surgery, injury, etc. More particularly it relates to treatment of wounds in irradiated individuals.
• the wound healing process is adversely effected by irradiation. Irradiation causes a delay in the overall process. The early phase inflammatory response is inhibited. The formation and maturation of granulation tissue is retarded. And the reepithelialization process is delayed. These result in an overall prolongation of healing time Gu et al., J Environ Pathol Toxicol Oncol. 1998; 17:117-23. Particular components of the wound healing process that are affected include infiltrating macrophages and neutrophils, blood vessels, fibroblasts, collagen synthesis and secretion. Ibid.
• a method for stimulating wound healing in a radiation-exposed mammal An effective amount of Substance P or an analog thereof is administered to a mammal that has been exposed to radiation and that has a wound.
• the analog is selected from the group consisting of [Met-OH 11 ]- substance P, [Met-OMe 1 ⁇ -substance P, [Nle"]-substance P, [Pro 9 ]-substance P, [Sar 9 ]-substance P, [Tyr 8 ]-substance P, [p-Cl-Phe 7 ' 8 ] -substance P, [Sar 9 ,Met (O 2 ) H ]- substance P, and analogs having the amino acid backbone RPKPQQFFGLM-NH 2 .
• Healing of the wound is stimulated.
• Figure 1 shows the tail with bite wounds of a mouse that was subjected to irradiation.
• Figure 2 shows the tail that had bite wounds of a mouse that was subjected to irradiation and treatment with [Sar 9 ,Met (O 2 ) n ]-substance P.
• Substance P RKPQQFFGLM-NH 2 ; SEQ ID NO: 1 or a bioactive analog thereof such as Sar 9 ,Met( ⁇ 2 )' '-Substance P can be administered to stimulate wound healing.
• the bioactive analog can be selected from the group consisting of [Met-OH n ]-substance P, [Met-OMe u ]-substance P, [Nle ⁇ ]-substance P, [Pro 9 ]-substance P, [Sar 9 ]-substance P, [Tyr 8 ] -substance P, Sar 9 , MeKO 2 ) 1 '-Substance P, and [p-Cl-Phe 7 ' 8] -substance P.
• NK-I NK-I receptor
• Compounds which have the same amino acid backbone as substance P can be routinely modified and tested for receptor agonist activity. Routine assays for such activities are known in the art and can be used.
• the substance P or analog can be administered by any method known in the art, including via aerosol inhalation. Intravenous, topical, intratracheal, intrabronchial, intramuscular, sublingual, and oral administrations can also be used. Suitable dosages include 0.05 to 5 nanomolar substance P or analog for administration, or 0.1 to 2 nanomolar, or 0.5 to 1.5 nanomolar. For aerosol administration dosages include 0.05 to 5 micromolar substance P or analog, preferably 0.1 to 2 micromolar, and more preferably 0.5 to 1.5 micromolar. For direct intramuscular injection a 2 micromolar solution can be used, for example. Other useful concentration ranges of substance P or its bioactive analog in an aerosol administered is between 0.001 and 75 ⁇ M.
• Concentrations for topical administration are in the range of 1 ⁇ M to 50 ⁇ M .
• Amounts to be administered are typically between 1 ⁇ M and 10 ⁇ M.
• Wounds which are amenable to treatment according to the present invention are those on the surface as well as internal to an animal body.
• the wounds may be caused by accident, disease, or purposefully.
• the wounds can, for example, be surgical wounds.
• Amenable wounds include but are not limited to cutaneous wounds, muscular wounds, osseus lesions, gastrointestinal anastamoses, decubitus ulcers, gastrointestinal ulcers, and burn wounds.
• the methods of the present invention can be applied to any mammal, including humans, horses, sheep, primates such as monkeys, apes, gibbons, chimpanzees, rodents such as mice, rats, guinea pigs, hamsters, ungulates such as cows.
• Example 1 The male mice fought while confined with four mice/bin. They sustained extensive tail wounds from biting. We then exposed the mice to either 7, 8, or 9 Gy 60 Cobalt gamma radiation in a single acute dose.
• [Sar ,Met(C>2) ]-substance P was administered by direct muscle injection in a 0.5 ml bolus at 2 micromolar concentration. Control animals received injections of normal saline. At 7 weeks post-radiation exposure, the control mice had unhealed tail wounds (see Fig. 1) while the [Sar 9 ,Met(O 2 )' ']-substance P -treated mice did not have any unhealed tail wounds (see Fig. 2).

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical & Material Sciences (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Medicinal Chemistry (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• General Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Gastroenterology & Hepatology (AREA)
• Immunology (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Epidemiology (AREA)
• Dermatology (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

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• 2005
  • 2005-10-25 AU AU2005299341A patent/AU2005299341A1/en not_active Abandoned
  • 2005-10-25 US US11/666,474 patent/US20080318869A1/en not_active Abandoned
  • 2005-10-25 EP EP05813067A patent/EP1809313A4/en not_active Withdrawn
  • 2005-10-25 CA CA002585265A patent/CA2585265A1/en not_active Abandoned
  • 2005-10-25 JP JP2007539081A patent/JP2008518020A/ja active Pending
  • 2005-10-25 WO PCT/US2005/038646 patent/WO2006047625A2/en not_active Ceased

Non-Patent Citations (1)

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