DE2209499C3 - Flat substrate with a collagen coating - Google Patents

Description

The invention relates to a flat substrate for medical and hygienic purposes and for wound dressings, in which one surface is coated with collagen is

Flat substrates that are coated with flaky, finely divided substances can be produced by a wide variety of processes (cf., for example, the DE-OS 20 54 752 and DE-AS 11 37 358). It is also already known, the various one-part substances on suitable by electrostatic deposition Apply carrier (see, for example, US Patents 255 035, 25 92 602, 3194 702, 32 02 539, 33 23 933, 34 57 000 and 34 92 144).

A method is known from US Pat. No. 3,563,200 in which a suspension of comminuted collagen is applied to a tissue used for treating a wound. A first electrode is attached above the suspension and a second electrode is attached in contact with the animal to be treated at a point remote from the treated tissue.A voltage is applied to both electrodes, whereby a layer of collagen fibers migrates to the tissue and is deposited there electrophoretically . The layer of collagen fibers deposited in this way forms a skin-like coating on the tissue which, however, has no hemostatic properties whatsoever

From Swiss patent specification 4 82 445 it is known to apply a collagen sol to a flat substrate apply, but even in this case the product obtained does not have any hemostatic properties having. The wound dressing material described therein is made from a collagen sol (a suspension of collagen fibers), the mucopolysaccharide be added, after which the mass is converted into a foam. After the foam is in the form of a If the film has solidified, the film is covered with a suitable film made of a plastic, such as polyvinyl chloride, tied together,

The object of the invention was now to provide a for medical and hygienic purposes as well as for To develop wound dressings suitable, collagen-coated, flat substrate that not only has a high Has absorbency and a good hemostatic effect, but is also particularly good can handle. It has been proven in practice demonstrated the handling of such flocked flat materials is sometimes a bit difficult as a result of the flakes detaching during handling, especially when the material has to be cut and otherwise handled.

It has now been found that this task

can be solved that one on the flat substrate

a fibrous, microcrystalline collagen in one

specific application amount by electrostatic

Deposits deposits

The invention relates to a flat substrate for medical and hygienic purposes and for wound dressings, in which one surface is coated with collagen, which is characterized in that the coating or covering on one surface is a fibrous, microcrystalline one Collagen in an application amount of 1 to 30 mg / cm ² is involved, with one end of electrostatically deposited collagen fibers adhering to the flat substrate. The planar substrate according to the invention, coated with finely divided microcrystalline collagen, is suitable for the production of bandages, surgical dressings, hemostatic swabs and cushions and it has the advantageous property that it excellently soaks up the exuding blood fluid on bleeding wounds and results in a reliable closure of the wound, which sutures or additional brackets, such as B. clamps, ties, etc., can be saved. Since it can also be handled excellently, this results in a considerable enrichment of the state of the art in the field of wound care, especially in emergencies.

According to a preferred embodiment, the fibrous, microcrystalline collagen is applied to the flat substrate ^{in an application amount of 2 to 20 mg / cm 2}

According to a further preferred embodiment, the structure containing collagen also contains pharmaceutical agents. Furthermore, the microcrystalline collagen used in the substrate according to the invention can contain additives which increase the wet strength common crosslinking agents included.

The microcrystalline collagen used according to the invention is a collagen substance, the production and properties of which are described in detail in US Pat. Nos. 3,393,080, 3,443,261 and 3,471,598. This is a solid, finely divided microcrystalline collagen which is in a physical state between that of the so swollen fibers and that of tropocollagen. This new physical form of collagen is microcrystalline and colloidal and it consists of bundles of accumulated tropocollagen units, the length of which varies between that of a single tropocollagen unit to just below 1 μm and diameter from about 25 nm to a few hundred nm. The microcrystalline collagen used according to the invention must contain at least about 1% by weight of colloidal collagen particles with a size of less than 1 μm. This microcrystalline collagen has unique properties for the formation of aqueous non-elastic gels in concentrations of 0.5% of dispersed salts, the resulting gel having a pH of 3.2 ± 0.2 and a practically ⁶ "> has a stable viscosity at 5'C over a period of at least 100 hours when stored in a closed container.

Genes and breakdown products of collagen, such as gelatin, are formed when left thick or their Viscosity increases sharply, with rubbery mixtures being formed.

As indicated in the above-referenced US Patents, finely divided microcrystalline collagen made from a naturally occurring collagen that is either in the form of pieces or in Form of skin or intestine that is dried and used under non-denaturic.-ending conditions Have been crushed to facilitate processing. The undenatured collagen obtained in this way is treated under controlled conditions with a very dilute acid whose pH value is within of the range 1.6 to 2.6. When the collagen-containing material is wet, the amount of des Water contained in it in the preparation of the acid solution necessary for the preparation of the collagen-containing Material to be used should be taken into account. The material is then in the presence of the dilute acid crushed to about 1 to 10% or more, preferably 25 to 85% or more, of the collagen-containing material have a particle size of less than 1 μm. It is not there crucial that the entire collagen-containing material is comminuted to a particle size of less than 1 μm since the resulting product is useful even if only about 10% or less have been crushed this way. However, best results are achieved when the material is coated with a Particle size of less than 1 μπι in a substantial higher concentration is present

For the production of microcrystalline colloidal collagen, the skin or the collagen-containing Material must be thoroughly soaked in the dilute acid at the prescribed pH.

When hydrochloric acid is used as an acid treatment agent and when freeze-dried in vacuo If cow hide is used as collagen raw material, it is crucial that the pH value of the hand solution does not exceed 2.6 to remove the microcrystalline colloidal collagen with subsequent fragmentation let develop. Optimal results at a concentration of about 1% solids are obtained with Acid solutions with a pH value in the order of magnitude of 5 tion of 2. Treatment with solutions with a pH below 1.6 generally results in a rapid degradation of the molecular weight with a similar structure of the acid-soluble tropocollagen and for Formation of other degradation products, like that caused by the so pronounced drop in apparent viscosity is detected.

The effect of the acid treatment is threefold. First of all, the acid serves to create a limited swelling to effect the fibers. Limited hydrolysis of selective peptide bonds within the non-crystalline or amorphous regions of the KoIIagenfaserchen, so that a subsequent mechanical Comminution an effortless fragmentation of the weakened morphology into microcrystalline particles «> allows the dimensions between those of Have tropocollagen and collagen fibrils. Third, some of the acid reacts with free primary ones Amino groups of collagen to form what could be called the collagen hydrochloride salt, which is naturally ionized in the presence of water.

After the acid treatment, the skin substance becomes one with the acid homogeneously distributed in it subjected to mechanical comminution to a portion thereof, e.g., at least about 10%, to particle size Bring <1 μπι. The preferred shredder for example a Waring mixer for low solids concentrations, continues the particles of the treated Collagen undergoes a strong shear action to cause a rupture and effective crushing of the to effect microcrystalline aggregates. High shear can also be exerted in other ways for example by extrusion through small nozzles, especially in the case of high solids concentrations (about 5%), as well as by other known techniques. Crushing is preferred continued well beyond the point where 10% of the product was one particle size Have <Ιμΐη, e.g. B. to 15 to 20% or even more of the product have been crushed to a colloidal size.

Hydrochloric acid is used as a preferred acid treatment agent only because it is relatively cheap is and brings effortless adaptability and controllability with it,;. Other acids, both inorganic and ionizable organic acids are also usable, e.g. B. sulfuric acid, Hydrobromic acid, phosphoric acid, cyanoacetic acid, acetic acid and citric acid. Sulfuric acid is true satisfactory, but controlling their effect is difficult. Citric acid can take the place of hydrochloric acid, hydrobromic acid, sulfuric acid, cyanoacetic acid occur because of their ability to stop swelling and hydrolysis of the Collagen fibers at the point where insoluble colloidal material is created and maintained remains while preventing rapid degradation of the material into a soluble product.

After the comminution is complete, the gels formed have a pH of about 2.6 to 3.8, with the special pH value depends on the pH value of the treatment acid. The pH value of the gels is preferably the have optimal properties, between 3.0 and j, 3.

To produce a 1% gel, for example 1 part finely ground cowhide, freeze-dried in a vacuum, with 100 parts of a hydrochloric acid solution treated, which had a pH of 2.25. After 15 minutes of treatment in a Waring mixer the gel had a pH of 3.25.

A 2% gel was prepared in the same way and had a pH of 33. If 1 g samples finely divided microcrystalline collagen were produced by drying these gels and the Samples were placed in 100 ml of distilled water, The partial hydrochloride salt of collagen ionized and the pH of the water dropped to about 3.1.

The microcrystalline collagen has good water absorption properties Products made on and from this material do not tend to settle in water to divide. Accordingly, the finely divided microcrystalline collagen is useful for the manufacture of fabrics and structures that can be used as wound dressings in surgical procedures.

For certain applications it is useful to remove the free fat material that is in the finely divided microcrystalline collagen may be present. This removal can be effected by making cellulosic fibers in the form of heavily bleached Kraftwood pulp or microcrystalline ko'k> idaler cellulose in a dispersion of the microcrystalline collagen can be added to the cellulosic material with appropriate mixing to be distributed evenly in the resulting dispersion

len. Subsequent filtering of the resulting dispersion, for example by normal pressure filtration, leads to a significant removal of the natural fatty substances originally in the collagen source material were present. Alternative methods of reducing such fatty substances to low levels Values consist in the extraction of the raw, undried hides or the corresponding collagen starting material with organic solvents such as acetone, which dissolve the fatty substances, or im Pressing the dispersions through cellulose paper or fabric filters under very high pressure. Such Filtration steps also help remove foreign matter or other contaminants, for example Pieces of hair and flesh tissue that are usually found in the finished microcrystalline collagen containing products are not desired.

Optionally, the wet strength of the microcrystalline collagen-containing material contained in the substrates according to the invention is used, can be improved by incorporating crosslinking agents into the Manufacturing processes are introduced, especially at the start of the crushing for the manufacture of the microcrystalline collagen. Typical crosslinking agents that are useful include the various Crosslinking agents based on formaldehyde, for example urea-formaldehyde precondensate and melamine-formaldehyde precondensate, Glyoxal, acetaldehyde, glutaraldehyde, potassium alum, chrome alum, iron alum, basic aluminum acetate, cadmium acetate, Copper acetate, barium hydroxide and water-soluble diisocyanates. The particular crosslinking agent used depends on the desired end use of the microcrystalline collagen containing product. the Crosslinking agents serve to improve the wet strength of the finished products. An added benefit is given by the use of certain crosslinking agents, namely an improvement in heat resistance of the finished product.

The products according to the invention, ie products with a layer or coating of microcrystalline collagen, are suitable wherever absorbent material is desired. z. B. for disposable diapers, sanitary napkins. Wipes, surgical sponges. Industrial and household sponges, swabs, applicators, tampons, surgical dressings or cigarette filters. If the microcrystalline collagen-containing structures according to the invention are to be used, for example, as hemostatic dressings or bandages, the collagen coating will normally be applied to the substrate in an amount in the range of 1 to 30 mg / cm ² , preferably in an amount of 2 to 15 - 20 mg / cm ² .

In the microcrystalline collagen-containing structures of the invention, a pharmaceutical or medical agent may be included. Such funds can be used during the process of Production of the microcrystalline collagen or in admixture with the finely divided microcrystalline Collagen are introduced in the manufacturing process, in which there is an electrostatic deposition of the finely divided microcrystalline collagen is used to produce structures according to the invention. Possibly Such agents can also be incorporated into the finely divided, microcrystalline collagen-containing structures are introduced, which have been prepared according to the invention, namely after the electrostatic Deposition of microcrystalline collagen.

The drawing, which shows schematically the production of a substrate according to the invention, is a fine-particle microcrystalline collagen contained within a shaft 11, which is above a suitable Substrate 12 is seated, which is moved on and through rollers 14 and fS. The substrate can be one Acting film made of cellulose, for example, with an aqueous gel containing collagen as the adhesive material can be coated and which runs past the lower outlet 11a of the shaft 11. Fine-particle microcrystalline Collagen that has received an electrostatic charge from a generator 16 falls through the lower outlet 11a of the shaft 11 on the passing Substrate 12, which is also, but opposite, charged electrostatically by generator 16 is.

As the finely divided microcrystalline collagen falls through the outlet 11a of the shaft 11, it is attracted to the oppositely charged surface of the substrate YZ and forms a uniform coating or layer of finely divided microcrystalline collagen thereon. Optionally, as shown, a dryer 18 can be provided to dry or harden any adhesive material that may be present on the surface of the substrate in order to allow the electrostatically deposited layer of finely divided microcrystalline collagen to adhere better. After passing through the dryer 18, the substrate, which is coated with finely divided microcrystalline collagen, runs. over roller 15 and is directed to its appropriate product take-up roller as shown.

The electrostatic deposition of the finely divided microcrystalline collagen on a corresponding charged substrate is particularly beneficial. This ensures a uniform coating of the Substrate with microcrystalline collagen causes this uniform coating with microcrystalline Collagen can be made on the substrate because the surface of the substrate is substantially uniform Charge with a polarity is opposite to that of the charged, finely divided one microcrystalline coil is while it emerges from the outlet Ua of the shaft 11. This is how it is possible to deposit a layer of finely divided microcrystalline collagen on all free surfaces of the substrate, including the areas of crevices and spaces that are normally difficult to reach. Furthermore, the resulting electrostatically deposited layer of finely divided microcrystalline collagen is in the Essentially uniform in appearance.

In practice, the finely divided, fibrous microcrystalline collagen tends to be so opposite to that charged substrate to be attracted to that one end of the fine microcrystalline collagen fibers first comes into contact with the substrate and remains adhered to it especially when the substrate Under these circumstances, the electrostatically deposited tend to be coated with an adhesive Fibers tend to be deposited with one end on the substrate, and this leads to the formation of a improved special coating with finely divided microcrystalline collagen. Such a coating From a technical point of view, it is unlikely to be anything other than electrostatic deposition be attainable.

Although the teaching is according to the invention as it has been shown schematically in the drawing

previously described as referring to the electrostatic deposition of a single layer microcrystalline collagen on a substrate, but it goes without saying that more complicated multilayer structures containing electrostatically deposited microcrystalline collagen can be produced can by making use of the teaching according to the invention Γ ^.

1 sheet of drawings

Claims (3)

Patent claims: 1. Flat substrate for medical and hygienic purposes and for wound dressings, in which one surface is coated with collagen, characterized in that the coating or covering on one surface is made of fibrous, microcrystalline collagen in an application amount of 1 to 30 mg / cm ² , with one end of electrostatically deposited collagen fibers adhering to the flat substrate. 2. Substrate according to claim 1, characterized in that it is contained in the collagen Structure also contains pharmaceutical agents. 3. Substrate according to claim 1 or 2, characterized in that the microcrystalline collagen contains additives of customary crosslinking agents which increase wet strength