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WO2004096367A1 - Materiau pour pansements contenant des piegeurs de radicaux - Google Patents

Materiau pour pansements contenant des piegeurs de radicaux Download PDF

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Publication number
WO2004096367A1
WO2004096367A1 PCT/CZ2004/000022 CZ2004000022W WO2004096367A1 WO 2004096367 A1 WO2004096367 A1 WO 2004096367A1 CZ 2004000022 W CZ2004000022 W CZ 2004000022W WO 2004096367 A1 WO2004096367 A1 WO 2004096367A1
Authority
WO
WIPO (PCT)
Prior art keywords
methacrylate
wound
dimethacrylate
characteristic
properties
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/CZ2004/000022
Other languages
English (en)
Inventor
Jiri Michalek
Pavel Novak
Ilja Straskraba
Jiri Vacik
Eva Wirthova
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.)
USTAV MAKROMOLEKULARNI CHEMIE AKADEMIE VED CESKE REPUBLIKY
Wilens Spolsro
Original Assignee
USTAV MAKROMOLEKULARNI CHEMIE AKADEMIE VED CESKE REPUBLIKY
Wilens Spolsro
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 USTAV MAKROMOLEKULARNI CHEMIE AKADEMIE VED CESKE REPUBLIKY, Wilens Spolsro filed Critical USTAV MAKROMOLEKULARNI CHEMIE AKADEMIE VED CESKE REPUBLIKY
Publication of WO2004096367A1 publication Critical patent/WO2004096367A1/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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • 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
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/24—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • 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
    • 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
    • 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

Definitions

  • the invention deals with a wound-cover material containing radical scavengers and method of its preparation.
  • hydrophilic materials are known for covers of wounds, which are based on alginates (Sorbalgon®, Paul Hartman, Heywood, Lanes., UK), polyurethanes (Cutifilm,
  • the subject of the present invention is a material for wound healing, containing radical scavengers, the essence of which is that the material consists of a polymer carrier based on lightly crosslinked hydrophilic polymers or copolymers from one or more monomers, a crosslinker and a physiological, biologically active substance .
  • radical- scavenging properties selected from the group of vitamins A, carotenoids, vitamins E, ubiquinones, flavonoids, nicotinamide, uric acid, bilirubin, lipoic acid, glutathione, melatonin.
  • hydrophilic polymers and copolymers are formed from the monomers selected from the group including 2-hydroxyethyl methacrylate, diethylene glycol methacrylate, triethylene glycol methacrylate, poly(ethylene glycol methacrylate), glycerol methacrylate, alkyl methacrylates, 2,3-dihydroxypropyl methacrylate, acrylic or methacrylic acid and their; salts, and containing, at the same time, up to 5 wt.% of crosslinker.
  • Diacrylate or dimethacrylate esters to advantage ethylene dimethacrylate, diethylene glycol dimethacrylate and triethylene glycol dimethacrylate, are used as crosslinkers.
  • the polymer carrier has the form of a flexible film, powder or gel with a dispersed or dissolved substance having properties of radical scavenger in amounts 0.0001-50 wt. %.
  • a unique property of the material for wound covers according to the invention is that it consists of well-known components, which underwent long-term clinical tests and which in the combination according to the invention show useful properties. The properties have not yet been utilized, according to the background art.
  • the material for wound covers according to the invention can have different forms depending on the method of preparation; each of the forms is suitable for a different wound type.
  • Elastic films are prepared by block or solution polymerization in the presence of a radical scavenger.
  • the radical scavenger is incorporated in the film by swelling with a solvent containing the dissolved scavenger.
  • the solvent acts in the film as plastifier and enables its good adherence to the wound.
  • the film protects the wound from external contamination, provides a damp medium and deactivates radicals. It can be easily removed without pain.
  • the material for wound covers according to the invention in the powder form is prepared by precipitation polymerization.
  • the radical scavenger is dissolved in a suspension of the powder in a solvent and the solvent is then evaporated.
  • the powder has the same functions as the film but, in addition, absorbs the wound exsudate up to a multiple of its original weight. The swollen powder is easily separated from the wound in the form of gel. If the material contains methacrylic acid or its salts, it acts also as an ion exchanger.
  • the change of ion medium in the wound affects favourably its healing (Resl V., Healing of Chronic Wounds, in Czech, Grada Publishing, Praha 1997).
  • the material for wound covers according to the invention in the gel form is obtained from the powder prepared by precipitation polymerization by mixing with a thermodynamically good solvent and a radical scavenger, possibly with addition of an emulgator.
  • solvents in particular poly(oxyethylene)s of different molecular weights can be used and their aqueous solutions.
  • the outstanding feature of the gel is its ability to adhere to the wound also in skin folds, where the application of film is not appropriate.
  • the application form is very advantageous in veterinary applications.
  • the effect of the material for wound covers consists in a synergistic effect of the damp cover of the wound and the ability to deactivate RONS.
  • the wounds treated with the material according to the invention heal without complications, without secondary infections and with successfully proceeding epithelization.
  • the material for wound covers according to the invention is suitable for the application in traumatic, surgical and chronic wounds.
  • the powder is applied to strongly weeping wounds and film or gel for weakly weeping wounds.
  • the effect of the material for wound covers can be supported by admixing other additives, in particular substances with antibacterial properties, such as antibiotics, corticoids or disinfection agents.
  • All application forms of the materials for wound covers can be sterilized by some well-known methods.
  • sterilization by ⁇ -radiation is suitable, for gels and films thermal sterilization in a steam autoclave.
  • a mixture of 5.00 g 2-hydroxyethyl methacrylate, 0.10 g ethylene dimethacrylate, 0.50 g benzoin ethyl ether, 4.83 g poly(ethylene glycol) 300 and 0.10 g retinol acetate was stirred for 10 min. After short bubbling with nitrogen, the polymerization mixture was transferred into a polymerization device consisting of two parallel polypropylene plates of the size 120x120x1 mm separated with a spacer of 0:8 mm thickness. The device was placed under a source of UV light for 30 min.
  • the obtained film was swollen in distilled water and then in an emulsion of the composition 47.5 % distilled water, 48 % poly(ethylene glycol) 300, 4 % tocopherol acetate and 0.5 % surfactant Polysorbate 80.
  • the film dimensions were adjusted to the 10x10 cm size, the film was sealed into an aluminium foil lined with polypropylene and sterilized with steam at 121 °C for 20 min.
  • Example 1 A mixture of 4.95 g 2-hydroxyethyl methacrylate, 0.10 g ethylene dimethacrylate, 2.97 g poly(ethylene glycol) 300, 1.98 g distilled water, 0.40 g tocopherol acetate and 0.05 g benzoin ethyl ether was stirred until all components dissolved and then polymerized by the method described in Example 1. A homogeneous opaque and elastic film was obtained with drawability of 250 %. The film was packed up and sterilized by the method described in Example 1.
  • a powdery polymer was prepared by the method described in Example 4 from 9.40 g 2-hydroxyethyl methacrylate, 0.10 g ethylene dimethacrylate, 0.50 g sodium methacrylate and 0.10 g 2,2'-azobisisobutyronitrile in 100 g of toluene.
  • the polymer was further worked up by the procedure described in Example 4. On equilibrium swelling, the powder absorbed 3.2 g of physiological saline of pH 7.3 per 1 g of dry matter.
  • Example 6 A powdery polymer was prepared by the method described in Example 4 from a solution of 9.40 g 2-hydroxyethyl methacrylate, 0.10 g ethylene dimethacrylate, 0.20 g methacrylic acid and 0.01 g 2,2'-azobisisobutyronitrile in 100 g of toluene.
  • the polymer was further worked up by the procedure described in Example 4. On equilibrium swelling, the powder absorbed 1.0 g of physiological saline of pH 7.3 per 1 g of dry matter.
  • Example 8 into 50 g of the emulsion prepared from 24.5 g distilled water, 25.0 g poly(clhylcne glycol) 300, 0.4 g retinol acetate, and 0.10 g Polysorbate 80 was successively added, under stirring, 10.0 g of powdery polymer prepared by the method given in Example 4. The mixture was left standing for 24 h until a homogeneous opalescent gel formed. The gel was filled into glass vials, 15 g in each, and into polypropylene blisters, 2.0 g in each and sterilized in a steam autoclave at 121 °C for 20 min.
  • a powdery polymer was prepared by the method described in Example 4 from a solution of 4.90 g 2-hydroxyethyl methacrylate, 5.00 g 2,3-dihydroxypropyl methacrylate, 0.10 g ethylene dimethacrylate, and 0.10 g 2,2'-azobisisobutyronitrile in 100 g of toluene.
  • the polymer was further worked up by the procedure described in Example 4. On equilibrium swelling, the powder absorbed 1.5 g of physiological saline of pH 7.3 per 1 g of dry matter.
  • Example 12 Into the solution prepared by mixing 25.0 g 0.4% aqueous solution of amoxicillin and 25.0 g poly(ethylene glycol) 300 was successively added, under stirring, 10.0 g of the powdery polymer prepared by the method given in Example 4. The mixture was left standing for 24 h until a homogeneous opalescent gel formed. The gel was filled into glass vials, 15 g in each, and into polypropylene blisters, 2.0 g in each.
  • a bruised laceration on the ear auricle of a three-year tomcat was cleaned and irrigated with physiological saline. After a Shotrapen injection the wound was treated with the powder prepared according to Example 6. The powder was applied three times in 24-h intervals and - then the gel prepared by the method described in Example 8 was applied twice. A week after starting the treatment, the wound healed forming a scar with a small central focus of pure granulation tissue.
  • a wound of forearm and autopodium of the the upper left limb, with deep alterations of periosteum and articular capsule of a six-month German shepherd was cleaned, irrigated with hydrogen peroxide, physiological saline and generally repaired.
  • the wound was treated with the gel prepared according to Example 8. The gel was applied twice in a 24-h interval; the next dressing was after 48 h. On day five of the treatment, the wound was without inflammation and with pure granulations. Three weeks after starting the treatment, the wound was healed forming a scar, with no pain on palpation. The dog normally loaded the limb.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials Engineering (AREA)
  • Dermatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention se rapporte à un matériau pour pansements, qui comprend un support polymère à base de polymères ou de copolymères hydrophiles faiblement réticulés formés à partir d'un ou de plusieurs monomères, un agent de réticulation et une substance physiologique biologiquement active ayant des propriétés de piégeur de radiaux. Les monomères sont choisis dans le groupe contenant du méthacrylate de 2-hydroxyéthyle, du méthacrylate de diéthylène glycol, du méthacrylate de triéthylène glycol, du méthacrylate de poly(éthylène glycol), du méthacrylate de glycérol, des méthacrylates alkyle, de l'acide acrylique ou méthacrylique et ses sels. Les agents de réticulation sont constitués par des esters de diacrylate ou de diméthacrylate (de préférence du diméthylacrylate d'éthylène, du diméthylacrylate de diéthylène glycol, et du diméthacrylate de triéthylène glycol) dans des quantités pouvant représenter jusqu'à 5 % en poids du mélange de polymérisation. La substance physiologique biologiquement active ayant des propriétés de piégeage des radicaux est choisie dans le groupe des vitamines A, des caroténoïdes, des vitamines E, des ubiquinones, des flavonoïdes, de la nicotinamide, de l'acide urique, de la bilirubine, de l'acide lipoïque, de la glutathione et de la mélatonine.
PCT/CZ2004/000022 2003-04-28 2004-04-22 Materiau pour pansements contenant des piegeurs de radicaux Ceased WO2004096367A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CZPV2003-1187 2003-04-28
CZ20031187A CZ295826B6 (cs) 2003-04-28 2003-04-28 Materiál pro krytí ran obsahující lapače radikálů

Publications (1)

Publication Number Publication Date
WO2004096367A1 true WO2004096367A1 (fr) 2004-11-11

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Application Number Title Priority Date Filing Date
PCT/CZ2004/000022 Ceased WO2004096367A1 (fr) 2003-04-28 2004-04-22 Materiau pour pansements contenant des piegeurs de radicaux

Country Status (2)

Country Link
CZ (1) CZ295826B6 (fr)
WO (1) WO2004096367A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2428577A (en) * 2005-08-01 2007-02-07 James Bruce Clapp Free radical scavenging wound powder
JP2010501590A (ja) * 2006-08-23 2010-01-21 アメリカ合衆国 酸化的ストレス関連疾患の治療または予防方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0535446A1 (fr) * 1991-09-30 1993-04-07 BONISCONTRO E GAZZONE S.r.l. Compositions pharmaceutiques à usage topique contenant un agent de chelation, un tocophérol et un agent antimicrobien
WO1994023707A1 (fr) * 1993-04-20 1994-10-27 Hexal Pharma Gmbh Pansement a substance active
WO2000030694A1 (fr) * 1998-11-24 2000-06-02 Johnson & Johnson Consumer Companies, Inc. Revetement utile comme distributeur de principe actif sur les pansements et les bandages
WO2001007064A1 (fr) * 1999-07-21 2001-02-01 Thione International, Inc. Compositions antioxydantes synergiques servant a lutter contre les hemorroides et d'autres types d'inflammations ano-rectales

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0535446A1 (fr) * 1991-09-30 1993-04-07 BONISCONTRO E GAZZONE S.r.l. Compositions pharmaceutiques à usage topique contenant un agent de chelation, un tocophérol et un agent antimicrobien
WO1994023707A1 (fr) * 1993-04-20 1994-10-27 Hexal Pharma Gmbh Pansement a substance active
WO2000030694A1 (fr) * 1998-11-24 2000-06-02 Johnson & Johnson Consumer Companies, Inc. Revetement utile comme distributeur de principe actif sur les pansements et les bandages
WO2001007064A1 (fr) * 1999-07-21 2001-02-01 Thione International, Inc. Compositions antioxydantes synergiques servant a lutter contre les hemorroides et d'autres types d'inflammations ano-rectales

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2428577A (en) * 2005-08-01 2007-02-07 James Bruce Clapp Free radical scavenging wound powder
JP2010501590A (ja) * 2006-08-23 2010-01-21 アメリカ合衆国 酸化的ストレス関連疾患の治療または予防方法

Also Published As

Publication number Publication date
CZ20031187A3 (cs) 2004-12-15
CZ295826B6 (cs) 2005-11-16

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