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WO2006007846A2 - Pansement - Google Patents

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Publication number
WO2006007846A2
WO2006007846A2 PCT/DK2005/000496 DK2005000496W WO2006007846A2 WO 2006007846 A2 WO2006007846 A2 WO 2006007846A2 DK 2005000496 W DK2005000496 W DK 2005000496W WO 2006007846 A2 WO2006007846 A2 WO 2006007846A2
Authority
WO
WIPO (PCT)
Prior art keywords
dressing
spi
antioxidant
wound
serine protease
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
PCT/DK2005/000496
Other languages
English (en)
Other versions
WO2006007846A3 (fr
Inventor
Flemming Reissig Jensen
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.)
Coloplast AS
Original Assignee
Coloplast AS
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 Coloplast AS filed Critical Coloplast AS
Publication of WO2006007846A2 publication Critical patent/WO2006007846A2/fr
Publication of WO2006007846A3 publication Critical patent/WO2006007846A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/44—Medicaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/428—Vitamins, e.g. tocopherol, riboflavin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/432—Inhibitors, antagonists
    • A61L2300/434—Inhibitors, antagonists of enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures

Definitions

  • the invention relates to dressings, particularly dressings for promoting the healing of a wound, comprising enzyme inhibitors. Furthermore, the invention relates to a composition and use of such composition for promoting the healing of a wound.
  • Type 2 diabetes typically affect people over 65, due to the underlying clinical complications typically associated with chronic wounds, such venous and arterial insufficiency, diabetes and trauma caused by bed-rest.
  • Type 2 diabetes is expected to grow significantly in the next 20 years; in the US type 2 diabetes is estimated to increase by 14 % per year, doubling every 5 years, an increase inevitably resulting in a corresponding increase in the number of diabetic foot ulcers.
  • Serine Proteases are hydrolytic enzymes naturally occurring in Man. This family of enzymes has many functions in the human physiology, e.g. in the immune system, developmental, cancer and inflammatory pathways.
  • Human Neutrophil Elastase (HNE, synonyms: elastase, leukocyte elastase, lysosomal elastase) is a Serine Protease, and is one of several hydrolytic enzymes contained in the azurophil granules of human neutrophils.
  • Elastase is involved in the inflammatory response upon wounding, and as such, Elastase is involved in the degradation of foreign material ingested during phagocytosis, as well the degradation of extracellular matrix components such as collagen, Fibronectin and Elastin. It has been demonstrated that levels of elastase activity are elevated in chronic wound fluids and that elastase contributes to the overall increase in proteolytic activity of the chronic wound environment.
  • Elastase present in chronic wound fluid, is the enzyme responsible for the degradation of several extracellular constitutive matrix proteins such as fibronectin, collagen and Elastin as well as the degradation of peptide growth factors such as PDGF and TGF- ⁇ .
  • cell surface receptors for peptide growth factors may themselves be functionally inactivated by the actions of elastase. Under normal physiological conditions, the activity of serine proteases such as elastase is tightly controlled by naturally occurring inhibitors, such as SLPI, AAT or Elafin.
  • SLPI serine protease
  • SLPI is a 11.7 kDa unglycosylated protein [Bingle L, Thorax 1996, 51 :1273-1274], known to be a potent inhibitor of several serine proteases such as human neutrophil elastase, mast cell chymase and Cathepsin G.
  • SLPI Is a hydrophobic cationic protein and will bind readily to elastase and some of its substrates such as elastin and other extraxcellular matrix components.
  • SLPI can furthermore inhibit elastin-bound elastase. The interaction between SLPI and elastase is reversible.
  • SLPI loose anti-elastase activity when exposed to reactive oxygen species (ROS), due to oxidation of the active site methionine to the corresponding sulphoxide.
  • ROS reactive oxygen species
  • Reactive oxygen species are known to exist in high concentrations in chronic wound exudates.
  • SLPI has recently been implicated in the healing of chronic wounds, as well as a number of other documented in vitro biological and physiological properties, such as anti-microbial (anti-bacterial, anti ⁇ fungal), anti-inflammatory and anti viral.
  • Elastase is controlled-by the ⁇ -1 -proteinase inhibitor ( ⁇ -1 -antitrypsin), a serum protease inhibitor that can penetrate into various tissues.
  • ⁇ -1 -antitrypsin a serum protease inhibitor that can penetrate into various tissues.
  • Protease inhibitors normally prevent damage to connective tissue caused by leakage of MMP's, however elastase is known to proteolytically inactivate the specific MMP-inhibitor, TIMP's.
  • elastase itself may participate in proteolytic activation of collagenase and gelatinase zymogens.
  • AAT is a 52 kDa extensively glycosylated protein, known to be a very potent inhibitor of human neutrophil elastase. Originally isolated from human plasma, AAT can now be produced recombinantly in a less glycosylated version. AAT is the major serum inhibitor of human neutrophil elastase, and the main source of inhibition of elastase in fluids/solution. As seen in the case of SLPI, AAT is the subject of oxidative inactivation through the oxidation of the active site methionine, to the corresponding sulfoxide.
  • ROS reactive oxygen species
  • Antioxidants e.g. vitamin E, vitamin C and Raxofelast, a synthetic vitamin E analogue
  • the beneficial effects arise from the potential to neutralize damaging ROS; thereby preventing the above outlined detrimental effects.
  • International patent application No. WO 01/64132 discloses a wound dressing with protease lowering activity provided by protease inhibitors.
  • the dressing may further comprise therapeutically beneficial substances such as antibiotics or vitamins. The reference is silent with respect to use of antioxidants.
  • the present invention facilitates accelerated healing of chronic wounds as well as improving tissue, minimising the risk of reoccurrence.
  • One object of the present invention is to provide a dressing comprising a Serine Protease Inhibitor (SPI), which is not susceptible to degradation.
  • SPI Serine Protease Inhibitor
  • Another object of the invention is to provide a dressing comprising a SPI, which can be sterilized without significant loss of activity.
  • a third object of the present invention is to provide composition for enhancing the healing of a wound.
  • a fourth object of the preset invention is to use a novel composition for the healing of wounds.
  • a fifth object of the present invention is to provide a composition and a dressing comprising a Serine Protease Inhibitor (SPI), being stable during the production, transport, storage and sterilisation.
  • SPI Serine Protease Inhibitor
  • the invention relates to a dressing for promoting the healing of a wound, said dressing comprising a Serine Protease Inhibitor (SPI), wherein the dressing further comprises one or more antioxidants.
  • SPI Serine Protease Inhibitor
  • the invention provides the use of a Serine Protease Inhibitor (SPI) in combination with an antioxidant, to achieve an improved and synergistic effect on the healing of wounds, especially chronic wounds, such as pressure sores or leg ulcers.
  • the invention also includes the use of antioxidants as stabilizing entities during the production, transport, storage and sterilisation of compositions, such as pharmaceutical compositions or medical devices, containing oxidatively sensitive active pharmaceutical entities, such as SPPs.
  • the antioxidant may be functioning to protect the SPI from oxidative damage during production, sterilisation, transport and storage as well as oxidative damage from reactive oxygen species (ROS) in the wound environment.
  • ROS reactive oxygen species
  • the antioxidant may comprise Vitamin E or derivatives or analogues thereof.
  • the antioxidant is water-soluble. This may especially be desired when having an aqueous environment during production of the dressing, as well as it may enhance the solubility into the wound site and wound exudates.
  • the SPI and the antioxidant may be incorporated in the dressing, e.g. by mixing into one or more of the components of the dressing.
  • the compound may be incorporated in an adhesive or it may be incorporated in an absorbent element, such as a foam or other suitable absorbent material.
  • the SPI and the antioxidant are released from the dressing. This renders it possible for the compound to enter deeper into the wound site and carry out its function there.
  • the dressing of the present invention may further comprise one or more active ingredients besides SPI.
  • the dressing according to the invention may comprise one or more active ingredients, e.g. a pharmaceutical medicament.
  • active ingredients e.g. a pharmaceutical medicament.
  • pharmaceutical medicaments such as bacteriostatic or bactericidal compounds, e.g. iodine, iodopovidone complexes, chloramine, chlorohexidine, silver salts such as sulphadiazine, silver nitrate, silver acetate, silver lactate, silver sulphate, silver sodium thiosulphate or silver chloride, zinc or salts thereof, metronidazol, sulpha drugs, and penicillin's, pain-killing agents, tissue-healing enhancing agents, e.g.
  • RGD tripeptides and the like proteins, amino acids such as taurine, vitamins such ascorbic acid, enzymes for cleansing of wounds, e.g. pepsin, trypsin and the like, proteinase inhibitors or metalloproteinase inhibitors such as Illostat or ethylene diamine tetraacetic acid, cytotoxic agents and proliferation inhibitors for use in for example surgical insertion of the product in cancer tissue and/or other therapeutic agents which optionally may be used for topical application, emollients, retinoids or agents having a cooling effect which is also considered an aspect of the invention.
  • the active ingredient may also comprise odour controlling or odour reducing material such as charcoal.
  • the dressing further comprises a growth factor.
  • the invention also relates to a method for promoting the healing of a wound by co-administrating an effective amount of SPI and antioxidant to a wound.
  • the invention relates to a composition for promoting the healing of a wound, said composition comprising a Serine Protease Inhibitor (SPI) and one or more antioxidants.
  • SPI Serine Protease Inhibitor
  • the composition comprising a serine protease inhibitor in combination with an antioxidant is used for the treatment of inflammation in cutanous ulcers, such as, but not limited to, burns, venous leg ulcers, pressure ulcer and diabetic foot ulcers.
  • composition comprising a serine protease inhibitor in combination with an antioxidant is used to prevent and treat tissue destruction due to inflammation.
  • composition comprising a serine protease inhibitor in combination with an antioxidant is used to improve the quality of tissue in a healed wound and to minimise the risk of reoccurrence.
  • composition of the present invention may comprise one or more serine protease inhibitors such as, but not limited to, alfa-1 -antitrypsin (AAT), secretory leukocyte protease inhibitor (SLPI) or Elafin in combination with one or more antioxidants such as, but not limited to, Raxofelast, vitamin E, vitamin C or derivatives or analogues thereof.
  • AAT alfa-1 -antitrypsin
  • SLPI secretory leukocyte protease inhibitor
  • Elafin in combination with one or more antioxidants such as, but not limited to, Raxofelast, vitamin E, vitamin C or derivatives or analogues thereof.
  • the composition may be used for promoting healing of chronic wounds such as, but not limited to, pressure ulcers, arterial leg ulcers, venous leg ulcers and diabetic foot ulcers.
  • composition comprising a serine protease inhibitor in combination with an antioxidant may be delivered to the tissue injury as a topical treatment, e.g. via a pharmaceutically acceptable delivery vehicle.
  • the invention relates to the use of a composition for promoting the healing of a wound, said composition comprising a Serine Protease Inhibitor (SPI) and one or more antioxidants.
  • a composition for achieving improved or accelerated healing of chronic wounds such as pressure sores, leg ulcers and diabetic foot ulcers, through the synergistically acting co ⁇ administration of a composition consisting of a Serine Protease Inhibitor (SPI), such as Secretory Leukocyte Protease Inhibitor (SLPI) or alfa-1 -antitrypsin (AAT) and an antioxidant, such as vitamin E or derivatives or analogues thereof.
  • SPI Serine Protease Inhibitor
  • SLPI Secretory Leukocyte Protease Inhibitor
  • AAT alfa-1 -antitrypsin
  • the invention provides for the use of a composition comprising a serine protease inhibitor in combination with an antioxidant for the treatment of tissue injury.
  • the composition can either be manifested as a pharmaceutical composition or a medical device and can be administered IV, PO, subQ, topically or IP.

Landscapes

  • Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne l'utilisation d'un inhibiteur de sérine protéase (SPI) en combinaison avec un antioxydant, afin d'obtenir un effet synergique et amélioré sur la cicatrisation de plaies, notamment de plaies chroniques, telles que les escarres de décubitus ou les ulcères de jambes. L'invention concerne également l'utilisation d'antioxydants en tant qu'éléments stabilisants au cours de la production, du transport, du stockage et de la stérilisation de compositions, telles que des compositions pharmaceutiques, ou de dispositifs médicaux, contenant des éléments pharmaceutiques actifs sensibles à l'oxydation, tels que les SPI.
PCT/DK2005/000496 2004-07-16 2005-07-14 Pansement Ceased WO2006007846A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DKPA200401122 2004-07-16
DKPA200401122 2004-07-16

Publications (2)

Publication Number Publication Date
WO2006007846A2 true WO2006007846A2 (fr) 2006-01-26
WO2006007846A3 WO2006007846A3 (fr) 2006-02-23

Family

ID=35448116

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK2005/000496 Ceased WO2006007846A2 (fr) 2004-07-16 2005-07-14 Pansement

Country Status (1)

Country Link
WO (1) WO2006007846A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180289836A1 (en) * 2017-04-05 2018-10-11 Drexel University Complexes and methods of reducing inflammation

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5190917A (en) * 1986-12-24 1993-03-02 John Lezdey Treatment of psoriasis
US6174859B1 (en) * 1999-04-06 2001-01-16 J & D Sciences, Inc. Method of treatment
US6262020B1 (en) * 2000-02-15 2001-07-17 Alphamed Pharmaceuticals Corp. Topical wound therapeutic compositions

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180289836A1 (en) * 2017-04-05 2018-10-11 Drexel University Complexes and methods of reducing inflammation
US12070507B2 (en) 2017-04-05 2024-08-27 Drexel University Complexes and methods of reducing inflammation

Also Published As

Publication number Publication date
WO2006007846A3 (fr) 2006-02-23

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