DE202021002536U1 - Collagen wound mat providing metabolic energy for the healing of chronic wounds - Google Patents
Collagen wound mat providing metabolic energy for the healing of chronic wounds Download PDFInfo
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- DE202021002536U1 DE202021002536U1 DE202021002536.7U DE202021002536U DE202021002536U1 DE 202021002536 U1 DE202021002536 U1 DE 202021002536U1 DE 202021002536 U DE202021002536 U DE 202021002536U DE 202021002536 U1 DE202021002536 U1 DE 202021002536U1
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/01—Non-adhesive bandages or dressings
- A61F13/01008—Non-adhesive bandages or dressings characterised by the material
- A61F13/01012—Non-adhesive bandages or dressings characterised by the material being made of natural material, e.g. cellulose-, protein-, collagen-based
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/00051—Accessories for dressings
- A61F13/00063—Accessories for dressings comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/42—Phosphorus; Compounds thereof
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- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0004—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing inorganic materials
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- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0028—Polypeptides; Proteins; Degradation products thereof
- A61L26/0033—Collagen
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- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
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- A—HUMAN NECESSITIES
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/112—Phosphorus-containing compounds, e.g. phosphates, phosphonates
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- A61L2400/00—Materials characterised by their function or physical properties
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Abstract
Wundmatte/-auflage (1) zur Heilung chronischer Wunden, dadurch gekennzeichnet, dass das zugrundeliegende Material aus komprimierten Kollagen (2) besteht, in das anorganisches Polyphosphat in Form von amorphen Magnesiumpolyphosphat-Nanopartikeln (3) eingebettet ist, wobei die Nanopartikel bei Kontakt mit Wundsekret (13) in ein gelartiges Koazervat (14) umgewandelt werden. Wound mat / pad (1) for healing chronic wounds, characterized in that the underlying material consists of compressed collagen (2) in which inorganic polyphosphate in the form of amorphous magnesium polyphosphate nanoparticles (3) is embedded, the nanoparticles on contact with Wound secretion (13) can be converted into a gel-like coacervate (14).
Description
Chronische Wunden wie venöse Beingeschwüre, diabetische Fußgeschwüre und Druckgeschwüre stellen ein globales Gesundheitsproblem dar. Allein in den Vereinigten Staaten leiden 3 - 6 Millionen Menschen an derartigen nicht oder nur schwer heilenden Wunden. Infolge des sich ändernden Lebensstils und der Zunahme der älteren Bevölkerung haben chronische Wunden sich zu einer zunehmenden finanziellen Belastung der Gesundheitssysteme entwickelt. In den entwickelten Ländern entfallen 3% der gesamten Gesundheitsausgaben auf die Versorgung chronischer Wunden.Chronic wounds such as venous leg ulcers, diabetic foot ulcers, and pressure sores are a global health problem. In the United States alone, 3 to 6 million people suffer from such non-healing or difficult-to-heal wounds. As a result of changing lifestyles and the increase in the elderly population, chronic wounds have become an increasing financial burden on health systems. Chronic wound care accounts for 3% of total health care spending in developed countries.
Die derzeit nach dem Stand der Technik hergestellten Wundmatten/-auflagen sind nicht in der Lage, die für die Heilung chronischer Wunden benötigte metabolische Energie zu liefern. Die Wundheilung ist ein stark energieverbrauchender Prozess, der Stoffwechselenergie in Form von Adenosintriphosphat (ATP) benötigt. Mit fortschreitendem Alter oder metabolischen Erkrankungen wie Diabetes ist der Gefäßfluss beeinträchtig, wodurch die Versorgung der Haut mit Sauerstoff beeinträchtigt ist. Dadurch kann nicht mehr genug ATP für die Wundheilung gebildet werden.The wound mats / dressings currently produced according to the state of the art are not able to supply the metabolic energy required for the healing of chronic wounds. Wound healing is a highly energy-consuming process that requires metabolic energy in the form of adenosine triphosphate (ATP). With advancing age or metabolic diseases such as diabetes, the vascular flow is impaired, as a result of which the supply of oxygen to the skin is impaired. As a result, enough ATP can no longer be formed for wound healing.
Das sich dem Anmelder gestellte technische Problem bestand in der Entwicklung einer Wundmatte/-auflage, die in der Lage ist, zum einen die für die Wundheilung benötigte metabolische Energie über eine längere Zeitperiode zu liefern. Zum anderen sollte die Wundmatte/-auflage die Adhäsion von Zellen sowie die Einwanderung von Zellen ermöglichen und fördern einschließlich der Gefäßbildung (Mikrovaskularisation) und die in chronischen Wunden erhöhte Aktivität der Elastase von Neutrophilen hemmen. Darüber hinaus sollte das Material der Matten biokompatible, biologisch abbaubar, nicht-toxisch, nicht-immunogen und nicht-kanzerogen sein.The technical problem posed to the applicant consisted in the development of a wound mat / dressing which is able, on the one hand, to supply the metabolic energy required for wound healing over a longer period of time. On the other hand, the wound mat / dressing should enable and promote the adhesion of cells and the immigration of cells, including the formation of blood vessels (microvascularization) and inhibit the increased activity of neutrophil elastase in chronic wounds. In addition, the material of the mats should be biocompatible, biodegradable, non-toxic, non-immunogenic and non-carcinogenic.
Die hier präsentierte technologische Lösung dieses Problems besteht in einem neuartigen Typ von Wundmatten/-auflagen, der durch folgende Eigenschaften gekennzeichnet ist: 1. Der Bildung eines biologisch aktiven Koazervats nach Kontakt der in eine Matte aus mechanisch komprimierten Kollagen eingebetteten Magnesiumpolyphosphat-Nanopartikel mit Wundsekret. 2. Der enzymatisch über Enzyme im Wundsekret bzw. auf den Zelloberflächen aus dem dabei freigesetzten Polyphosphat gebildeten, für die Wundheilung benötigten, metabolischen Energie in Form von ATP. 3. Der Förderung der Adhäsion von Zellen (wie Myofibroblasten und Keratinozyten) und aktiven Zellmigration in die Wundmatte durch Zellaktivierung (Bildung von Mikrovilli). 4. Der Stimulierung der Gefäßneubildung (Mikrovaskularisation). Das eingebaute Polyphosphat ist ebenso wie die zugrundeliegende Kollagenmatrix biokompatible, biologisch abbaubar, nicht-toxisch, nicht-immunogen und nicht-kanzerogen. Weiterhin zeigen die erfindungsgemäßen Wundmatten/-auflagen in einer ihrer Ausführungsformen die Eigenschaft, die in chronischen Wunden erhöhte Aktivität der Neutrophilen-Elastase zu hemmen.The technological solution to this problem presented here consists of a new type of wound mats / dressings, which is characterized by the following properties: 1. The formation of a biologically active coacervate after contact of the magnesium polyphosphate nanoparticles embedded in a mat made of mechanically compressed collagen with wound secretion. 2. The metabolic energy in the form of ATP, which is formed enzymatically via enzymes in the wound secretion or on the cell surfaces from the polyphosphate released in the process and required for wound healing. 3. The promotion of the adhesion of cells (such as myofibroblasts and keratinocytes) and active cell migration into the wound mat through cell activation (formation of microvilli). 4. The stimulation of the formation of new vessels (microvascularization). Like the underlying collagen matrix, the built-in polyphosphate is biocompatible, biodegradable, non-toxic, non-immunogenic and non-carcinogenic. Furthermore, the wound mats / dressings according to the invention, in one of their embodiments, have the property of inhibiting the increased activity of neutrophil elastase in chronic wounds.
Das den Wundmatten/-auflagen zugrundeliegende Material besteht aus mechanisch komprimiertem Kollagen, in das als ATP-Vorstufe Polyphosphat in Form von amorphen Polyphosphat-Nanopartikeln eingebettet ist. Die amorphen Polyphosphat-Nanopartikel enthalten als Gegenion zu dem negativ geladenen Polyphosphat Magnesiumionen. Die somit vorliegenden Magnesiumpolyphosphat-Nanopartikel stimulieren die Zellmigration und Gefäßneubildung (Mikrovaskularisation). Die Wundmatten/-auflagen sind in proteinfreien wässrigen Lösungen stabil und werden bei Kontakt mit proteinhaltigen Flüssigkeiten wie Wundsekret in ein gelartiges Koazervat überführt.The material on which the wound mats / dressings are based consists of mechanically compressed collagen in which polyphosphate is embedded as an ATP precursor in the form of amorphous polyphosphate nanoparticles. The amorphous polyphosphate nanoparticles contain magnesium ions as a counterion to the negatively charged polyphosphate. The magnesium polyphosphate nanoparticles thus present stimulate cell migration and the formation of new blood vessels (microvascularization). The wound mats / dressings are stable in protein-free aqueous solutions and are converted into a gel-like coacervate when they come into contact with protein-containing liquids such as wound exudate.
In einer Ausführungsform bestehen die erfindungsgemäßen Wundmatten/- auflagen aus mechanisch komprimiertem Kollagen mit integrierten amorphen Magnesiumpolyphosphat-Nanopartikeln, die wie folgt hergestellt werden. Es wird Natriumpolyphosphat mit einer durchschnittlichen Kettenlänge von 40 Phosphateinheiten verwendet. Die Nanopartikel werden unter Verwendung eines Molverhältnisses von 2:1 zwischen Magnesiumchlorid und Natriumpolyphosphat (basierend auf Phosphat) hergestellt. Der pH wird auf 10 eingestellt. Die gebildeten Partikel werden durch Filtration gesammelt, mit Ethanol gewaschen und getrocknet. Zur Herstellung der mit amorphen Magnesiumpolyphosphat-Nanopartikeln beladenen Kollagenmatten werden 30 mg der Nanopartikel zu 2 ml einer bei 4°C gehaltenen Suspension von Rinderkollagen Typ I (5 mg/ml) in 0,1 M Essigsäure pH 3,6, enthaltend 1 mM Phenylmethylsulfonylfluorid, in eine Petrischale (Durchmesser 50 mm) gegeben und mit 2 ml 1 M Natronlauge neutralisiert. Nach Inkubation über Nacht bei 37°C (5% CO2-Atmosphäre) werden die Matten zweimal mit phosphatgepufferter Kochsalzlösung und anschließend mit Ethanol (70%) gewaschen. Danach werden die erhaltenen Gelkissen auf einen Filterpapierstapel (Whatman-3MM-Blotting-Papier) gelegt und nach Auflegen eines Nylon-Mesh-Filters (100 µm) mit einem Gewicht von 20 g für 20 min bis zu einer Schichtdicke von 1 bis 1,3 mm komprimiert. Aufbewahrt werden die Matten in Ethanol. In dieser Ausführungsform zeigen die erfindungsgemäßen Wundmatten/-auflagen die Eigenschaft, Polyphosphat mit optimaler Kinetik freizusetzen (30% der eingebauten Menge nach 2 Tagen).In one embodiment, the wound mats / dressings according to the invention consist of mechanically compressed collagen with integrated amorphous magnesium polyphosphate nanoparticles, which are produced as follows. Sodium polyphosphate with an average chain length of 40 phosphate units is used. The nanoparticles are made using a 2: 1 molar ratio between magnesium chloride and sodium polyphosphate (based on phosphate). The pH is adjusted to 10. The formed particles are collected by filtration, washed with ethanol and dried. To produce the collagen mats loaded with amorphous magnesium polyphosphate nanoparticles, 30 mg of the nanoparticles are added to 2 ml of a suspension of bovine collagen type I (5 mg / ml) in 0.1 M acetic acid pH 3.6, containing 1 mM phenylmethylsulfonyl fluoride, kept at 4 ° C , placed in a Petri dish (diameter 50 mm) and neutralized with 2 ml of 1 M sodium hydroxide solution. After incubation overnight at 37 ° C. (5% CO 2 atmosphere), the mats are washed twice with phosphate-buffered saline solution and then with ethanol (70%). The gel cushions obtained are then placed on a stack of filter paper (Whatman 3MM blotting paper) and, after placing a nylon mesh filter (100 μm) with a weight of 20 g, for 20 min up to a layer thickness of 1 to 1.3 mm compressed. The mats are stored in ethanol. In this embodiment, the wound mats / dressings according to the invention have the property of releasing polyphosphate with optimal kinetics (30% of the installed amount after 2 days).
In einer weiteren Ausführungsart der Erfindung werden die Matten während der Anwendung beim Patienten regelmäßig mit einer lösliches Natriumpolyphosphat (unmittelbar verfügbares Polyphosphat) und amorphe Calciumpolyphosphat-Nanopartikel (Depotform) enthaltenden Lösung befeuchtet, die folgendermaßen hergestellt wird: Eine wässrige Phosphatpuffer-Lösung (120 mM; pH 6,5), enthaltend 80 mM Natriumchlorid wird mit 20% (Vol./Vol.; Endvolumen) Propylenglykol versetzt, um der Lösung antimikrobielle und antimykotische Eigenschaften zu verleihen. Dann werden 300 µg/g Natriumpolyphosphat und 30 µg/g Calciumpolyphosphat-Nanopartikel hinzugegeben. Bei diesem Verhältnis zwischen löslichem Polyphosphat und Polyphosphat-Nanopartikeln (10:1) zeigen die erfindungsgemäßen Wundmatten/- auflagen die überraschende Eigenschaft, die Neutrophilen-Elastase zu hemmen. Die Präparation der benötigten Calciumpolyphosphat-Nanopartikel erfolgt analog dem Herstellungsverfahren der Magnesiumpolyphosphat-Nanopartikel aus Calciumchlorid (anstelle von Magnesiumchlorid) und Natriumpolyphosphat mit einer durchschnittlichen Kettenlänge von 40 Phosphateinheiten mit einem Molverhältnis von 2:1 und bei einem pH von 10.In a further embodiment of the invention, the mats are regularly with a soluble during use on the patient Sodium polyphosphate (immediately available polyphosphate) and amorphous calcium polyphosphate nanoparticles (depot form) containing solution, which is prepared as follows: An aqueous phosphate buffer solution (120 mM; pH 6.5) containing 80 mM sodium chloride is mixed with 20% (vol / Vol .; final volume) propylene glycol is added to give the solution antimicrobial and antifungal properties. Then 300 µg / g sodium polyphosphate and 30 µg / g calcium polyphosphate nanoparticles are added. With this ratio between soluble polyphosphate and polyphosphate nanoparticles (10: 1), the wound mats / dressings according to the invention show the surprising property of inhibiting neutrophil elastase. The required calcium polyphosphate nanoparticles are prepared in the same way as the magnesium polyphosphate nanoparticles are made from calcium chloride (instead of magnesium chloride) and sodium polyphosphate with an average chain length of 40 phosphate units with a molar ratio of 2: 1 and a pH of 10.
Durch Wahl geeigneter Bedingungen während der mechanischen Kompression des Kollagens können die Maschengrößen der Matten und somit deren Eigenschaften im Hinblick auf die Zellpenetration angepasst werden.By choosing suitable conditions during the mechanical compression of the collagen, the mesh sizes of the mats and thus their properties with regard to cell penetration can be adapted.
Die Vorteile der hier beschriebenen Wundmatten/-auflagen bestehen darin, dass sie nicht nur die Zelladhäsion und Zellmigration fördern, sondern auch die zur Heilung chronischer Wunden erforderliche metabolische Energie in Form von ATP bereitstellen. Darüber hinaus fördern die Wundmatten/-auflagen die Gefäßneubildung (Mikrovaskularisation), hemmen die in chronischen Wunden erhöhte Aktivität der Elastase von Neutrophilen, sind biokompatibel und bioabbaubar und zeigen keine toxischen, kanzerogenen oder immunogenen Eigenschaften. Wirkprinzip: Nach Kontakt mit Peptiden/Protein (Wundsekret) werden die Nanopartikel in ein Koazervat überführt, in dem das aus den Nanopartikeln freigesetzte Polyphosphat enzymatisch, durch Zusammenwirken der im Wundsekret bzw. an den Zelloberflächen vorhandenen Enzyme alkalische Phosphatase und Adenylatkinase, in metabolisch nutzbare Energie in Form von ATP überführt wird.The advantages of the wound mats / dressings described here are that they not only promote cell adhesion and cell migration, but also provide the metabolic energy required for the healing of chronic wounds in the form of ATP. In addition, the wound mats / dressings promote the formation of new blood vessels (microvascularization), inhibit the increased activity of neutrophil elastase in chronic wounds, are biocompatible and biodegradable and show no toxic, carcinogenic or immunogenic properties. Active principle: After contact with peptides / protein (wound secretion), the nanoparticles are transferred to a coacervate in which the polyphosphate released from the nanoparticles is converted into metabolically usable energy through the interaction of the alkaline phosphatase and adenylate kinase enzymes present in the wound secretion or on the cell surfaces is converted in the form of ATP.
Die Methode zur Herstellung der amorphen Magnesiumpolyphosphat-Nanopartikel ist in folgenden Anmeldungen offengelegt:
- Patent
EP 3220967B8 - Patent
US 10307350B2 - Patent ZL 201580067850.6. Morphogenetically active amorphous calcium polyphosphate nanoparticles for therapeutic applications. Erfinder: Müller WEG. 11/2015.
- Patentanmeldung
GB201701403D0
- patent
EP 3220967B8 - patent
US 10307350B2 - Patent ZL 201580067850.6. Morphogenetically active amorphous calcium polyphosphate nanoparticles for therapeutic applications. Inventor: Müller WEG. 11/2015.
- Patent application
GB201701403D0
Eine Übersicht über den Stand der Technik bei Polyphosphat ist in folgender Zeitschrift veröffentlicht:
-
Müller WEG, Schröder HC, Wang XH (2019)
-
Müller WEG, Schröder HC, Wang XH (2019)
Ein Ausführungsbeispiel der Erfindung wird nachfolgend anhand der
-
1 die Wundmatte/-auflage(1) , bestehend aus komprimierten Kollagenfasern(2) und darin eingebetteten amorphen Magnesiumpolyphosphat-Nanopartikeln(3) ; Querschnitt. -
2 ein Schema der bei der Bildung der Kollagenmatten ablaufende Fibrillenbildung nach Neutralisierung einer Suspension von Tropokollagen(4) (pH 3,6) über Prokollagen(5) zu Kollagenfasern(2) sowie Einbau von Magnesiumpolyphosphat-Nanopartikeln(3) . -
3 ein Schema der Vorrichtung zu mechanischen Kompression von Kollagen mit Filterpapierstapel(6) , Lochblech aus Edelstahl(7) , Nylon-Mesh-Filter(8) , perforierter Platte(9) , Kollagen-Magnesiumpolyphosphat-Matte(10) und Druckstempel bzw. Gewicht(11) . -
4 ein Schema der Verdichtung der Kollagenmatte bei der mechanischen Kompression(12) sowie der Umwandlung der Magnesiumpolyphosphat-Nanopartikel(3) bei Kontakt mit Peptid/Protein-haltigem Wundsekret(13) in ein Koazervat(14) .
-
1 the wound mat / pad(1) , consisting of compressed collagen fibers(2) and amorphous magnesium polyphosphate nanoparticles embedded therein(3) ; Cross-section. -
2 a diagram of the fibril formation taking place during the formation of the collagen mats after neutralization of a suspension of tropocollagen(4) (pH 3.6) via procollagen(5) to collagen fibers(2) and incorporation of magnesium polyphosphate nanoparticles(3) . -
3 a scheme of the device for mechanical compression of collagen with a stack of filter paper(6) , Perforated sheet made of stainless steel(7) , Nylon mesh filter(8th) , perforated plate(9) , Collagen-magnesium polyphosphate mat(10) and stamp or weight(11) . -
4th a diagram of the compaction of the collagen mat during mechanical compression(12) as well as the conversion of the magnesium polyphosphate nanoparticles(3) after contact with peptide / protein-containing wound exudate(13) into a coacervate(14) .
BezugszeichenlisteList of reference symbols
- (1)(1)
- Wundmatte/-auflageWound mat / pad
- (2)(2)
- KollagenfaserCollagen fiber
- (3)(3)
- Magnesiumpolyphosphat-NanopartikelMagnesium polyphosphate nanoparticles
- (4)(4)
- TropokollagenTropocollagen
- (5)(5)
- ProkollagenProcollagen
- (6)(6)
- FilterpapierstapelFilter paper stack
- (7)(7)
- Lochblech aus EdelstahlStainless steel perforated sheet
- (8)(8th)
- Nylon-Mesh-FilterNylon mesh filter
- (9)(9)
- Perforierter PlattePerforated plate
- (10)(10)
- Kollagen-Magnesiumpolyphosphat-MatteCollagen Magnesium Polyphosphate Mat
- (11)(11)
- GewichtWeight
- (12)(12)
- Mechanische KompressionMechanical compression
- (13)(13)
- WundsekretWound secretions
- (14)(14)
- KoazervatCoacervate
ZITATE ENTHALTEN IN DER BESCHREIBUNGQUOTES INCLUDED IN THE DESCRIPTION
Diese Liste der vom Anmelder aufgeführten Dokumente wurde automatisiert erzeugt und ist ausschließlich zur besseren Information des Lesers aufgenommen. Die Liste ist nicht Bestandteil der deutschen Patent- bzw. Gebrauchsmusteranmeldung. Das DPMA übernimmt keinerlei Haftung für etwaige Fehler oder Auslassungen.This list of the documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.
Zitierte PatentliteraturPatent literature cited
- EP 3220967 B8 [0010]EP 3220967 B8 [0010]
- US 10307350 B2 [0010]US 10307350 B2 [0010]
- GB 201701403 D0 [0010]GB 201701403 D0 [0010]
Zitierte Nicht-PatentliteraturNon-patent literature cited
- Müller WEG, Schröder HC, Wang XH (2019) [0011]Müller WEG, Schröder HC, Wang XH (2019) [0011]
Claims (10)
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB201701403D0 (en) | 2017-01-27 | 2017-03-15 | Mueller Werner E G | Formulation based on polyphosphate microparticles for topical treatment of difficult-to-heal wounds |
US10307350B2 (en) | 2014-11-17 | 2019-06-04 | Nanotecmarin Gmbh | Morphogenetically active amorphous calcium polyphosphate nanoparticles for therapeutic applications |
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2021
- 2021-08-05 DE DE202021002536.7U patent/DE202021002536U1/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10307350B2 (en) | 2014-11-17 | 2019-06-04 | Nanotecmarin Gmbh | Morphogenetically active amorphous calcium polyphosphate nanoparticles for therapeutic applications |
EP3220967B1 (en) | 2014-11-17 | 2019-06-19 | NanotecMARIN GmbH | Morphogenetically active amorphous calcium polyphosphate nanoparticles containing retinol for therapeutic applications |
GB201701403D0 (en) | 2017-01-27 | 2017-03-15 | Mueller Werner E G | Formulation based on polyphosphate microparticles for topical treatment of difficult-to-heal wounds |
Non-Patent Citations (1)
Title |
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Müller WEG, Schröder HC, Wang XH (2019) |
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