AT165549B - Process for the production of hemostatically acting plugs and bandages - Google Patents
Process for the production of hemostatically acting plugs and bandagesInfo
- Publication number
- AT165549B AT165549B AT165549DA AT165549B AT 165549 B AT165549 B AT 165549B AT 165549D A AT165549D A AT 165549DA AT 165549 B AT165549 B AT 165549B
- Authority
- AT
- Austria
- Prior art keywords
- sep
- thrombin
- solution
- plugs
- gelatin
- Prior art date
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
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
-
- 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
- A61L15/425—Porous materials, e.g. foams or sponges
-
- 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
- A61L15/64—Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2389/00—Characterised by the use of proteins; Derivatives thereof
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hematology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Materials For Medical Uses (AREA)
Description
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Verfahren zur Herstellung von hämostatisch wirkenden Pfropfen und Verbänden
In der Chirurgie werden bereits hämostatisch wirkende, aus Fibrin-und CellulosederivatSchwämmen bestehende Pfropfen und Verbände benützt, die eine Thrombinlösung enthalten. Diese Pfropfen und Verbände werden so gebrauchsfertig gemacht, dass man sie unmittelbar vor der Verwendung in die Thrombinlösung eintaucht. Diese Verwendung macht es notwendig, dass die Schwämme aus wasserunlöslichem Material hergestellt werden, da sie sonst bei der Benetzung mit der Thrombinlösung zusammenfallen würden. Solche Schwämme haben den grossen Nachteil, dass sie vom Organismus bedeutend schlechter resorbiert werden als lösliche Substanzen.
Um diesem Nachteil zu begegnen, verwenden verschiedene Autoren statt diese Schwämme lösliche Gelatine-Gelee, die sie kurz vor Gebrauch in eine Thrombinlösung eintauchen. Die Durchtränkung eines solchen Gelees mit der Thrombinlösung ist aber schwierig und verläuft sehr langsam ; ferner können die Pfropfen und Verbände, wenn sie mit der Thrombinlösung vollgesogen sind, nicht lange aufbewahrt werden, da das Thrombin in Gegenwart von Wasser nicht stabil ist und sehr rasch an Wirksamkeit verliert. Ausserdem wurde festgestellt, dass das Thrombin eine Verminderung des Geliervermögens der Gelatine bewirkt.
Es wurde nun gefunden, dass man hämostatisch wirkende Pfropfen und Verbände aus löslicher
Gelatine dadurch herstellen kann, dass man einer
Gelatinelösung Thrombin zusetzt, die erhaltene
Lösung in Schaum vei wandelt, diesen Schaum bei tiefer Temperatur im Vakuum trocknet und den erhaltenen thrombinhaltigen Gelatine- schwamm in geeignete Form bringt. Gemäss diesem Verfahren werden hämostatisch wirkende
Pfropfen und Verbände erhalten, die aus einer leicht löslichen Gelatinethrombinmasse von watte- ähnlichem Aussehen bestehen. Diese Pfropfen und Verbände brauchen vorher nicht in Thrombin- lösung getaucht zu werden, sie können unmittelbar auf die Wunde, wo sie eine sehr rasche Hämostase bewirken, gelegt werden.
Das aus der Wunde ausfliessende Blut wird in die schwammige Masse aufgesogen und löst den Gelatinebestandteil auf ; das dabei freiwerdende Thrombin bewirkt sofort die Verwandlung des Fibrinogens in Fibrin. Auf der Wunde bildet sich auf diese Weise ein Fibrin- film, welcher den Verschluss der Wunde bewirkt und den Blutfluss hemmt. Dieser Film haftet so stark auf der Oberfläche der Wunde, dass ein zusätzlicher Verband nicht notwendig ist.
In vitro wird die Wirksamkeit der Pfropfen folgendermassen gezeigt.
In einem Reagensglas (Durchmesser zirka 1 cm) werden einige Pfropfen zu einer Kolonne von ungefähr 5 cm Höhe lose eingestampft. Darauf werden 5 ccm 37 C warmes Plasma gegossen. Das Plasma wird in die schwammartige Masse eingesogen und gerinnt so schnell, dass das Reagensglas unmittelbar nach dem Eingiessen umgekehrt werden kann, ohne dass das Plasma abfliesst.
Der Gelatine-Thrombinmasse können verschiedene Antiseptica zugesetzt werden, ohne dass die Wirksamkeit der Verbände und Pfropfen dadurch leiden würde : Thymol, ein Gemisch von p-Oxy-benzoesäuremethyl-und-propylester, Sulfanilamide, wie 5-Sulfanilamido-3,4-dimethyl-isoxazol und vemarbungsbeschleunigende Sub-
EMI1.1
Die Gelatine übt auf das in Lösung befindliche Thrombin eine deutliche Schutzwirkung aus. So verliert eine wässerige, 50" Gelatine enthaltende Thrombinlösung langsamer an Wirksamkeit als eine gleiche Lösung ohne Gelatine.
EMI1.2
<tb>
<tb>
Wässerige
<tb> Wässerige <SEP> Thrombin- <SEP> und
<tb> Thrombinlosung <SEP> Gelantinelosung
<tb> 5 <SEP> 500 <SEP> Th. <SEP> E <SEP> ccm <SEP> 7 <SEP> 500 <SEP> Th <SEP> E <SEP> ccm
<tb> nach <SEP> 24 <SEP> Stunden <SEP> 4.000 <SEP> 7.500
<tb> # <SEP> 48 <SEP> # <SEP> 2.500 <SEP> 5.500
<tb> # <SEP> 72 <SEP> # <SEP> 350 <SEP> 4.000
<tb>
Beispiel 1 : Zu l00ccm destilliertem Wasser werden 5 g Blattgelatine zugesetzt, worauf auf 80 C erwärmt wird. Die erhaltene etwas trübe Lösung wird warm durch ein Seitz-Filter filtriert und, wenn notwendig, auf einen pH-Wert von 6, 6 gestellt.
Nun werden zu 50 ccm der erhaltenen, auf 20 C abgekühlten Lösung 10 ccm einer Thrombinlösung mit einem Thrombingehalt von 10.000 Einheiten pro Kubikzentimeter zugesetzt. Diese Thrombinlösung Wird mit Hilfe eines Thrombinpräparates hergestellt, dessen Gehalt titrimetrisch zu 100 Th. E bestimmt wurde. Es bildet sich eine
<Desc/Clms Page number 2>
lochte Trübung) die durch Sterilisierung mittels eines Seitz-Filters entfernt wird.
Die Hare Lösung wird durch Einblasen von steriler Luft mittels einer Sinterglasplatte und durch Schlagen mit Hilfe eines Schlagbesens in einem voluminösen Schaum verwandelt. Dieser wird dann auf ein- Blatt ausgebreitet, bei tiefer Temperatur eingefroren und im Hochvakuum bei-5"C entwässert.
Beispiel 2 : In 100 ccm warmem destilliertem Wasser werden 70 mg Thymol gelöst, der Lösung werden 5 Gelatine zugesetzt und das Ganze auf 80 C erwärmt. Im übrigen wird wie im Beispiel 1 weiter gearbeitet.
Beispiel 3 : In 100 ccm destilliertem Wasser werden 20 mg p-Oxy-benzoesäuremethylester und
80 mg p-Oxybenzoesäurepropylester gelöst. Die
Lösung wird mit 5 g Gelatine versetzt, auf 80 C erwärmt und im übrigen wie im Beispiel 1 weiter- verarbeitet.
Beispiel 4 : 5g Gelatine werden mit 90ccm destilliertem Wasser auf 800 C erwärmt. In der warmen Lösung werden 2 fein pulverisierte
5-Sulfanilamido-3, 4-dimethyl-isoxazol suspen- diert. Das PH wird durch Zusatz von 5 bis 10 ccm normaler Natronlauge auf 6, 6 gestellt, worauf sich das SuKanilamid auflöst. Man erwärmt auf 80 Q C und verfährt im übrigen wie im Beispiel 1.
Beispiel 5 : In 100 ccm destilliertem Wasser werden 0, 28 g Panthenol, [d (+)--Dioxy-ss, ss- dimethylbutyryl-Y'-oxypropylamid] gelöst. Man setzt 5 Gelatine zu, erwärmt das Ganze auf 800 C und verfährt im übrigen wie im Beispiel 1.
PATENTANSPRÜCHE :
1. Verfahren zur Herstellung von hämostatisch wirkenden Pfropfen und Verbänden, dadurch gekennzeichnet, dass man einer Gelatinelösung Thrombin zusetzt, die erhaltene Lösung in
Schaum verwandelt, diesen Schaum bei tiefer Temperatur im Vakuum trocknet und den so erhaltenen thrombinhaltigen Gelatineschwamm in geeignete Form bringt.
<Desc / Clms Page number 1>
Process for the production of hemostatically acting plugs and bandages
In surgery, plugs and dressings that already have a hemostatic effect and consist of fibrin and cellulose derivative sponges and contain a thrombin solution are used. These plugs and dressings are made ready for use by immersing them in the thrombin solution immediately prior to use. This use makes it necessary that the sponges are made of water-insoluble material, since otherwise they would collapse when wetted with the thrombin solution. Such sponges have the major disadvantage that they are much more poorly absorbed by the organism than soluble substances.
In order to counter this disadvantage, various authors use soluble gelatin jelly instead of these sponges, which they immerse in a thrombin solution shortly before use. The impregnation of such a jelly with the thrombin solution is difficult and takes place very slowly; Furthermore, the plugs and dressings, if they are soaked with the thrombin solution, cannot be stored for long, since the thrombin is not stable in the presence of water and very quickly loses its effectiveness. In addition, it was found that the thrombin causes a reduction in the gelling capacity of the gelatin.
It has now been found that hemostatic plugs and dressings can be made from soluble
Gelatin can be made by having a
Gelatin solution thrombin adds the obtained
The solution is converted into foam, this foam is dried at low temperature in a vacuum and the resulting thrombin-containing gelatin sponge is brought into a suitable shape. According to this procedure, they become hemostatic
Obtain plugs and bandages, which consist of a readily soluble gelatin thrombin mass of cotton-like appearance. These plugs and dressings do not need to be immersed in thrombin solution beforehand; they can be placed directly on the wound, where they cause a very rapid hemostasis.
The blood flowing out of the wound is absorbed into the spongy mass and dissolves the gelatin component; the thrombin that is released immediately causes the fibrinogen to be converted into fibrin. In this way, a fibrin film forms on the wound, which closes the wound and inhibits the flow of blood. This film adheres so strongly to the surface of the wound that an additional dressing is not necessary.
In vitro the effectiveness of the plug is shown as follows.
In a test tube (diameter approx. 1 cm) a few plugs are loosely tamped to form a column approx. 5 cm high. Then 5 cc of 37 C warm plasma are poured. The plasma is sucked into the spongy mass and coagulates so quickly that the test tube can be turned upside down immediately after pouring without the plasma flowing out.
Various antiseptics can be added to the gelatin-thrombin mass without impairing the effectiveness of the dressings and plugs: thymol, a mixture of methyl and propyl p-oxybenzoate, sulfanilamides such as 5-sulfanilamido-3,4-dimethyl isoxazole and scarring-accelerating sub-
EMI1.1
The gelatine has a clear protective effect on the thrombin in solution. For example, an aqueous thrombin solution containing 50 "gelatin loses its effectiveness more slowly than an identical solution without gelatin.
EMI1.2
<tb>
<tb>
Watery
<tb> Aqueous <SEP> Thrombin- <SEP> and
<tb> thrombin solution <SEP> gelatin solution
<tb> 5 <SEP> 500 <SEP> Th. <SEP> E <SEP> ccm <SEP> 7 <SEP> 500 <SEP> Th <SEP> E <SEP> ccm
<tb> after <SEP> 24 <SEP> hours <SEP> 4,000 <SEP> 7,500
<tb> # <SEP> 48 <SEP> # <SEP> 2,500 <SEP> 5,500
<tb> # <SEP> 72 <SEP> # <SEP> 350 <SEP> 4,000
<tb>
Example 1: 5 g of leaf gelatin are added to 100ccm of distilled water, and the mixture is then heated to 80.degree. The slightly cloudy solution obtained is filtered warm through a Seitz filter and, if necessary, adjusted to a pH of 6.6.
10 cc of a thrombin solution with a thrombin content of 10,000 units per cubic centimeter are now added to 50 cc of the resulting solution, which has been cooled to 20 ° C. This thrombin solution is produced with the help of a thrombin preparation, the content of which was determined titrimetrically to be 100 Th. E. One forms
<Desc / Clms Page number 2>
perforated cloudiness) which is removed by sterilization using a Seitz filter.
The Hare solution is transformed into a voluminous foam by blowing in sterile air through a sintered glass plate and by whipping with a whisk. This is then spread out on a sheet, frozen at a low temperature and drained in a high vacuum at -5 "C.
Example 2: 70 mg of thymol are dissolved in 100 cc of warm distilled water, 5 gelatine are added to the solution and the whole is heated to 80.degree. Otherwise, the procedure is as in Example 1.
Example 3: In 100 cc of distilled water, 20 mg of p-oxy-benzoic acid methyl ester and
80 mg of propyl p-oxybenzoate dissolved. The
5 g of gelatin are added to the solution, the mixture is heated to 80 ° C. and otherwise processed as in Example 1.
Example 4: 5 g of gelatin are heated to 800 ° C. with 90 cc of distilled water. In the warm solution are 2 finely powdered
5-sulfanilamido-3, 4-dimethyl-isoxazole suspended. The pH is adjusted to 6.6 by adding 5 to 10 cc of normal sodium hydroxide solution, whereupon the SuKanilamide dissolves. It is heated to 80 ° C. and the rest of the procedure is as in Example 1.
Example 5: 0.28 g of panthenol, [d (+) -dioxy-ss, s-dimethylbutyryl-Y'-oxypropylamide] are dissolved in 100 cc of distilled water. 5 gelatine are added, the whole is heated to 800 ° C. and the rest of the procedure is as in example 1.
PATENT CLAIMS:
1. A process for the production of hemostatically acting plugs and dressings, characterized in that thrombin is added to a gelatin solution and the solution obtained is in
Foam is transformed, this foam is dried at low temperature in a vacuum and the resulting thrombin-containing gelatin sponge is brought into a suitable shape.
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH2350347A CH264752A (en) | 1947-06-03 | 1947-06-03 | Process for the manufacture of carriers for pharmaceuticals. |
Publications (1)
Publication Number | Publication Date |
---|---|
AT165549B true AT165549B (en) | 1950-03-15 |
Family
ID=38468378
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AT165549D AT165549B (en) | 1947-06-03 | 1948-05-12 | Process for the production of hemostatically acting plugs and bandages |
Country Status (6)
Country | Link |
---|---|
US (1) | US2558395A (en) |
AT (1) | AT165549B (en) |
CH (1) | CH264752A (en) |
DE (1) | DE915973C (en) |
DK (1) | DK73956C (en) |
ES (1) | ES183694A1 (en) |
Families Citing this family (84)
Publication number | Priority date | Publication date | Assignee | Title |
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CH303082A (en) * | 1950-12-18 | 1954-11-15 | Hoechst Ag | Process for the production of a durable thrombin preparation of increased effectiveness. |
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DE2702356A1 (en) * | 1977-01-21 | 1978-07-27 | Gottlieb Sheldon K | Repairing depressed cutaneous scars - using fibrin stabiliser and plasma |
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Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE474093C (en) * | 1927-07-30 | 1929-03-26 | Erich Freund Dr | Process for the production of hemostatic and wound-healing bandages and plasters |
US2166074A (en) * | 1937-04-09 | 1939-07-11 | Sharp & Dohme Inc | Gelatinous colloids |
US2398077A (en) * | 1940-04-29 | 1946-04-09 | Parke Davis & Co | Blood coagulating product and method of obtaining same |
-
1947
- 1947-06-03 CH CH2350347A patent/CH264752A/en unknown
-
1948
- 1948-03-15 DK DK87948AA patent/DK73956C/en active
- 1948-03-26 US US17366A patent/US2558395A/en not_active Expired - Lifetime
- 1948-05-12 AT AT165549D patent/AT165549B/en active
- 1948-05-14 ES ES0183694A patent/ES183694A1/en not_active Expired
-
1949
- 1949-11-26 DE DEH633A patent/DE915973C/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
US2558395A (en) | 1951-06-26 |
DE915973C (en) | 1954-08-02 |
CH264752A (en) | 1949-10-31 |
ES183694A1 (en) | 1948-07-04 |
DK73956C (en) | 1952-03-31 |
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