EP3920990A1

EP3920990A1 - Biodegradable membrane

Info

Publication number: EP3920990A1
Application number: EP20703734.2A
Authority: EP
Inventors: Bastian Christ; Sabine Amberg-Schwab; Jörn PROBST
Original assignee: Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Current assignee: Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Priority date: 2019-02-07
Filing date: 2020-02-05
Publication date: 2021-12-15
Also published as: WO2020161151A1; DE102019201550A1; US20220118162A1

Abstract

The invention relates to a biodegradable membrane on the basis of an organic-inorganic hybrid polymer, and to a process for producing same.

Description

Biodegradable membrane

The present invention relates to a biodegradable membrane based on an organic-inorganic hybrid polymer and a method for its production.

Adhesions are scarred strands of connective tissue that create an unnatural connection between different body tissues. They can be either congenital or acquired. Acquired adhesions are usually the result of an operation. But they can also develop in inflammatory diseases of the abdomen or in the context of endometriosis (disease of the uterine lining).

Postoperative adhesions occur despite the best possible surgical technique and tissue-sparing surgical methods (such as minimally invasive interventions). They only cause discomfort in exceptional cases, but can then significantly affect the health and quality of life of those affected. pregnant. Adhesions that accompany operations in the abdominal cavity and surgical interventions in the uterus (e.g. excretion or removal of myomas) can be the reason for unwanted childlessness, chronic pelvic pain or narrowing and congestion of the intestine.

The formation of adhesions is only a natural reaction of wound healing, e.g. an injury to the peritoneum and / or organs. According to studies, they are found after 67 to 93% of all operations in which the peritoneum has been opened (G. Pados et al., Prevention of intra peritoneal adhesions in gynaecological surgery: theory and evidence, in Reproductive BioMedicine Online (2010) 21, 290-303). Nevertheless, it can happen that organs of the abdominal and pelvic area, e.g. B. loops of intestine, anei nander or attached to the peritoneum or the fallopian tubes and ovaries are tied and fixed in an unnatural way.

After extensive surgical interventions in the abdominal cavity, e.g. B. on the intestine, scar tissue forms, which can negatively affect intestinal motility. This occurs in 52-75% of cases after a colon resection (around 40,000 operations per year in Germany) (see S. Lyer et al., Economic Burden of Postoperative Ileus Associated With Colectomy in the United States, in J Manag Care Pharm. 2009; 15 (6): 485-94).

It is therefore of the greatest interest to develop a method with which the formation of adhesions can be suppressed or completely prevented.

Known methods are based on the use of various biocompatible barrier materials.

No. 7,172,765 B2 describes, for example, a method for reducing operative adhesions with the aid of a biodegradable membrane which consists of an electrospun fiber fabric without any filler or matrix material. The production of large areas or quantities of the membrane thus requires a lot of time. Another disadvantage is that electrospinning usually uses solvents that are toxic to cells, which are then carefully must be removed.

US Pat. No. 5,948,020 A likewise provides a bioresorbable membrane which can be inserted into human or animal tissue and there for some time prevents the undesired growth of other cells onto the tissue connected to the membrane. Structurally, the membrane is made up of fibers and a polymer matrix. For the production of both the fibers and the matrix, however, only degradable organic polymers are used. The disadvantage of these is that they usually show the effect of shrinking on contact with physiological media and do not remain dimensionally stable during the degradation.

Based on this prior art, it was the object of the present invention to provide a method with which the disadvantages known from the prior art are overcome and with which membranes can be produced in a simple manner that are biodegradable, but at least their barrier function Maintained over a period of three to seven days. Furthermore, the present invention was based on the task of providing a corresponding biodegradable membrane which at the same time has high dimensional stability and high flexibility.

This object is achieved with regard to the method with the features of Pa tentanspruchs 1 and with regard to the membrane with the features of Pa tentanspruchs 16. Further advantageous embodiments emerge from the dependent claims.

The process according to the invention for producing a biodegradable membrane based on an organic-inorganic hybrid polymer comprises the following process steps: Production of an inorganic sol by stirring a solution containing at least one aqueous solvent, an alkoxysilane and an acid at a temperature of at least 20 ° C (step a ); Converting the sol to a polymer-sol mixture by adding an end-group-functionalized, biodegradable organic polymer or by adding precursors of the polymer to the sol (step b); and applying the polymer-sol mixture to a front side of a film for Curing of the mixture to form a hybrid polymer layer (step c), a multiplicity of fibers being introduced into the mixture in an additional step d) before the mixture is cured.

With this method, a biodegradable membrane can be produced. Biodegradable is understood to mean that the membrane degrades on permanent contact with a physiological solution. For example, a buffered aqueous solution with a pH of 7.3 - 7.5 can be used as a physiological solution. In particular, an aqueous PBS solution containing 8.0 g / L NaCl, 0.2 g / L KCl, 1.42 g / L Na ₂ HP0 ₄ and 0.27 g / L can be used to test the biodegradability KH ₂ P0 _{4 contains} .

Furthermore, the method allows a membrane to be produced that is based on two main components. The first component is the organic inorganic hybrid polymer, which serves as the matrix material. The second component is the multitude of fibers that are embedded in the matrix. The properties of the two components surprisingly complement each other in such a way that the membrane resulting therefrom has a high tensile strength and at the same time a high degree of flexibility and flexibility.

The organic-inorganic hybrid polymer is obtained either by adding an end-group-functionalized, biodegradable organic polymer or by adding precursors of the polymer to the sol. While the precursors of the polymer are low molecular weight oligomers that are only precondensed to a small degree, the polymer itself is a high molecular weight polymer.

In addition, it was found that the membrane produced in this way does not shrink in the first few weeks despite permanent wetting with a physiological solution and the resulting progressive biodegradation. It initially retains its original dimensions. With a view to the use of the membrane as an adhesion barrier to avoid postoperative adhesions of various tissues, this prevents mechanical tensions from occurring during the healing process that could be perceived as unpleasant by the patient. Furthermore, the membrane produced by the method according to the invention has a dehesive effect after it has been applied to a cell tissue. This means that the membrane prevents neighboring cell tissue from growing.

Since the polymer-sol mixture can be produced as a one-pot reaction, the process is also suitable for transfer to an industrial scale and for the production of larger quantities.

The plurality of fibers are preferably introduced into the mixture in step d) by distributing fibers on the front side of the film before the mixture is applied (variant i) or by distributing the fibers on a surface of the mixture applied (variant ii). The fibers are particularly preferably aligned along a preferred direction or arranged in the form of a regular scrim or fabric.

These process variants (i and ii) are suitable for producing a membrane in which the fibers are integrated into the hybrid polymer layer produced by curing the mixture. The decision as to whether the fibers should be aligned along a preferred direction or arranged in the form of a scrim or fabric should be made taking into account the later application. If it is to be expected that the mechanical stress on the membrane is increased in one direction, there are many arguments in favor of aligning the fibers in a preferred direction. Orientation in a preferred direction can be achieved, for example, by spinning the fibers. This can be achieved through the spinning process by placing the fibers in a directional manner. This can e.g. take place via a programmable traversing table that moves at a defined speed in the x and y directions

In the method according to the invention it is also possible to carry out steps c) and d) several times and in each case alternately in succession. This affects the thickness of the membrane, which can be increased by applying the polymer-sol mixture several times. In addition, the distribution of the fibers in the cross-section of the membrane can be influenced.

If the fibers are carried out for the first time in process steps c) and d) before application of the mixture on the film and in the second execution of process steps c) and d) only after application of the polymer-sol mixture, the fiber density is increased on both sides of the membrane on the surface, while it is Inside the membrane is lowered. This is due to the fact that the fibers cannot distribute themselves evenly due to the viscosity of the polymer-sol mixture. Other fiber density distributions are achieved if a different approach is taken.

The following procedure is conceivable, for example: A layer of the polymer-sol mixture is applied to the film. The fibers are introduced before the mixture hardens. As the last step in the process, another layer of the polymer-sol mixture is applied. Fibers are no longer integrated into this layer.

The solution in step a) can be stirred at a temperature of 20 to 50.degree. C., preferably from 50 to 45.degree. C., in particular 40.degree. A stirring time of at least 7 hours is preferred, particularly preferably at least 8 hours, in particular at least 18 hours.

These process parameters ensure that the alkoxysilane is converted to polysiloxane and that a sol is formed in this way.

Furthermore, it is preferred if the mixture is applied in step c) by knife-coating or flooding of the front side of the film, the knife-coating preferably being carried out with the aid of a doctor blade, a spiral or a film-drawing device.

The alkoxysilane can be selected from the group consisting of tetramethyl orthosilicate, tetraethyl orthosilicate, tetrapropyl orthosilicate, tetraisopropyl orthosilicate, tetrabutyl orthosilicate, and mixtures thereof.

The end-group-functionalized, biodegradable organic polymer is preferably selected from the group consisting of end-group-functionalized polyesters, end-group-functionalized polyalcohols, end-group-functionalized polyoxazolines, end-group-functionalized polyanhydrides, end-group-functionalized group-functionalized polysaccharides, end-group-functionalized polyhydroxylalkanoates, end-group-functionalized proteins and mixtures thereof. The end-group-functionalized, biodegradable organic polymer is preferably an elastomer. The end group functionalization preferably consists of terminal hydroxyl groups,

Carboxylic acid groups, thiol groups, amine groups, epoxy groups and / or trialkoxysilane groups, particularly preferably terminal hydroxyl groups. A well-suited end-group-functionalized, biodegradable organic polymer is silanized polycaprolactam (PCL).

The end group functionalization of the organic polymer guarantees that it is at least partially linked covalently to the inorganic sol.

The structure of the organic polymers is arbitrary. Hybrid polymers with linear organic polymers as well as with branched or star-shaped organic polymers can be formed. The solubility of the organic polymers is more important. It is preferred here that the organic polymers dissolve well in aqueous or alcoholic solution or in a mixture of water and alcohol, or can at least be finely dispersed therein. Biodegradable elastomers are particularly preferably used as organic polymers.

It is advantageous if the acid which is used in process step a) is a sulfonic acid, preferably methanesulfonic acid. However, the acid can also be a mineral acid, for example HCl, H ₂ S0 ₄ , HN0 ₃ , Hl or H ₃ P0 ₄ . Mixtures of the aforementioned acids are also possible. The production of the biodegradable membrane is also facilitated if the solution in step a) of the method has a pH between 1 and 7, preferably between 1 and 3.

A suitable aqueous solvent is water or a mixture of water and an alcohol, tetrahydrofuran or toluene. Of these, the mixture of water and an alcohol, e.g. ethanol, is particularly recommended. Such a mixture makes it possible to manufacture the membrane without the use of solvents which are hazardous to health. Careful separation of solvent residues is therefore not necessary. The polymer in step b) of the process is preferably in a weight ratio of 0.1 to 10.0, particularly preferably from 0.5 to 8.0, in particular from 1.0 to 6.0, based on the mass of the in Step a) added sols prepared. In this way it is ensured that the weight fraction of the organic polymer in the hybrid polymer layer is at least 10% by weight, preferably at least 20% by weight. It is particularly preferred if the weight fraction of the organic polymer in the hybrid polymer layer is between 33 and 85% by weight.

Biodegradable fibers of any kind can be used as fibers. They can be organic, inorganic or hybrid in nature. The length of the fibers can also vary, so continuous fibers, long fibers but also shorter fiber pieces can be integrated into the polymer-sol mixture.

Preferably fibers from the group consisting of silica gel fibers, Ti0 ₂ -containing fibers, polyester fibers, polyanhydride fibers,

Polysaccharide fibers, polyhydroxyalkanoate fibers, protein fibers and mixtures thereof used, preferably from the group consisting of silica gel fibers and Ti0 ₂ -containing fibers, the fibers particularly preferably in a proportion of a maximum of 50 wt .-%, very particularly preferably a maximum of 33 wt. -%, in particular a maximum of 25% by weight, based on the total mass of hybrid polymer layer and fibers are used. Silica gel fibers have the advantage that they are structurally very similar to the inorganic sol that is formed from the alkoxysilane and can therefore be easily integrated into the polymer-sol mixture.

Particularly tear-resistant membranes are obtained when fibers with a tensile strength of at least 2800 MPa, preferably of at least

2950 MPa, in particular of at least 3000 MPa, can be used in the method according to the invention.

The fibers preferably have a diameter of 1 nm to 2 mm, preferably from 1 to 100 μm, in particular from 50 to 60 μm.

According to a further preferred embodiment, the Fibers to fibers obtained via the electrospinning method, preferably fibers obtained via the electrospinning method selected from the group consisting of silica gel fibers, Ti0 ₂ -containing fibers, polyester fibers, polyanhydride fibers, polysaccharide fibers, polyhydroxyalkanoate fibers, protein fibers and mixtures thereof. If silica gel is used as the material for these fibers, the fibers preferably have a diameter in the range from 100 nm to 5 miti, particularly preferably in the range from 500 nm to 2 miti.

In a variant of the method, the membrane is detached from the front side of the film after a drying time of at least 30 minutes, the front side of the film preferably being adhesive and / or consisting of ethylene-tetrafluoroethylene copolymer.

A particularly useful embodiment of the method from a medical point of view is achieved if at least one pharmacologically active compound is added in step a) or b) of the method or is used to impregnate the hybrid polymer layer after curing, the proportion of the pharmacologically active compound is chosen so that it is preferably from 1 to 20 wt .-% based on the total mass of

Hybrid polymer layer and fibers.

Particularly suitable pharmacologically active compounds are antibiotics and substances that reduce scarring. These compounds can be released during the degradation of the membrane. They can either be encapsulated or integrated in the membrane in their pure form. Encapsulation can take place through the formation of micelles, liposomes with the aid of block copolymers or inorganic particulate systems such as mesoporous or microporous particles. If pharmacologically active compounds are integrated into the membrane, the temperature during manufacture must never exceed the decomposition temperature of the active ingredient.

Furthermore, a membrane made of a biodegradable, organic, inorganic hybrid polymer and a large number of fibers is provided. The membrane can be decomposed and / or degraded by contacting it with a physiological solution, preferably an aqueous PBS solution containing NaCl, KCl, Na ₂ HP0 ₄ and KH ₂ P0 ₄ . When wetted with such a physiological solution, the membrane is particularly preferably degraded to at least 35% by weight of its total mass, preferably to at least 60% by weight of its total mass, within 64 days.

After 8 days of contact with an aqueous PBS solution, the membrane according to the invention is preferably at least 10% by weight of the total mass, preferably at least 20% by weight of the total mass, particularly preferably at least 25% by weight of the total mass, decomposed and / or degraded.

Furthermore, the membrane according to the invention is characterized in that it forms a barrier for the growth or ongrowth of human or animal cells over a period of at least three days, preferably 5 days, particularly preferably 7 days.

The membrane is produced by the method according to the invention described at the outset.

It is also conceivable that the membrane is provided with additional layers in this process or is printed.

The possibilities for using the membrane according to the invention are diverse.

Beyond in-vivo applications, the membrane can be used for material separation, in particular as a filtration membrane. With the help of the membrane, filtration membranes with active functions can be realized, the separation efficiency of which can be specifically adjusted through the polarity of the matrix and the structure of the hybrid film structure.

On the other hand, the membrane according to the invention can fen in surgical interventions in which the risk of postoperative formation of adhesions or scarring exists, in particular when inserting prostheses and Implants, or in pharmaceutical processes as active ingredient carriers, are used.

During surgical interventions, the membrane serves as an adhesion barrier or mechanical barrier and prevents cells from neighboring tissues from attaching to the tissue to which the membrane is attached. This results in an effective reduction in scarring, which is particularly relevant in cosmetic surgery.

However, the use of the membrane when inserting prostheses and implants also has great potential, since it leads to undisturbed and thus optimized ingrowth of the implants.

A pharmaceutical / therapeutic active substance plaster based on the membrane, on the other hand, can be used as an environmentally friendly active substance carrier that can be easily composted after use.

It is also conceivable to use the membrane with biodegradable sensors, biodegradable active implants, to cover open wounds and in the area of tissue engineering and cell cultivation.

The invention will be explained in more detail using the following examples and figures. They are only to be understood as examples and are not intended to limit the scope of the invention.

In Examples 1 and 2, test protocols are given according to which a membrane according to the invention can be produced. In methods 1-3, variants of Example 1 are described, which show how one can still get to the membrane according to the invention starting from the polymer-sol mixture and the fibers.

example 1

5 mol of tetraethoxysilane (TEOS) and 9.6 mol of ethanol are placed in a 2 L round-bottom flask and mixed at 40 ° C. in a polyethylene glycol bath at 200 rpm. Then 160 g of a 0.1 N methanesulfonic acid solution were added added dropwise. The reaction mixture was then heated to 40 ° C. for one day at a stirring speed of 200 rpm. With the aid of a rotary evaporator, 22 mol of ethanol were drawn off. The mass of the flask content was determined and twice the mass of silanized

Polycaprolactone triol (prepared according to Liu et al., Journal of Applied Polymer Science 109 (2008), pp. 1105-1113) is stirred in. This polymer-sol mixture is hereinafter referred to as "mixture 1".

After stirring at room temperature for 30 min, silica gel fibers (manufactured according to Emmert et al., RSC Adv., 2017, 7, 5708) with a diameter of 50 μm are placed on an ETFE film and flooded with mixture 1. The ETFE substrate was inclined at an angle of 25 ° so that the liquid was distributed over the fibers. After one day, the dried film was peeled off as a membrane from the ETFE foil.

Example 2:

5 mol of tetraethoxysilane (TEOS) and 9.6 mol of ethanol are placed in a 2 L round-bottom flask and mixed at 40 ° C. in a polyethylene glycol bath at 200 rpm. 160 g of a 0.1 N methanesulfonic acid solution were then added dropwise. The reaction mixture was then heated to 40 ° C. for one day at a stirring speed of 200 rpm. With the aid of a rotary evaporator, 22 mol of ethanol were drawn off. The mass of the flask content was determined and five times the mass of silanized

Polycaprolactone triol (prepared according to Liu et al., Journal of Applied Polymer Science 109 (2008), pp. 1105-1113) is stirred in. This polymer-sol mixture is hereinafter referred to as "mixture 2".

After stirring at room temperature for 30 min, fibers (produced according to Emmert et al., RSC Adv., 2017, 7, 5708

“Nanostructured surfaces of biodegradable silica fibers enhance directed amoeboid cell migration in a microtubule-dependent process”) with a diameter of 50 μm and applied with a doctor blade with the prepared mixture 2 using a film applicator. The paint film applicator had a film width of 225 μm one day the dried film was peeled off as a membrane from the ETFE foil. Example B:

A mixture 2 is produced analogously to Example 2. Then, according to method 3, the mixture is knife-coated over the fibers placed on an ETFE film.

Method 1:

Mixture 1 is applied in the liquid-viscous state to a film using a doctor blade. Then fibers are applied to the doctored layer and then another layer is spread over the fibers with a doctor blade. After a certain crosslinking time and after evaporation of solvents, the fiber-reinforced film can be peeled off the substrate.

Method 2:

Mixture 1 is applied in the liquid-viscous state to a film using a doctor blade. Then fibers are applied to the doctored layer and mixture 1 is flooded over the fibers. After a certain crosslinking time and evaporation of solvents, the fiber-reinforced film can be removed from the substrate.

Method 3:

Fibers are placed on a film and mixture 1 is applied in the liquid viscous state using a doctor blade. After a certain cross-linking time and evaporation of solvents, the fiber-reinforced film can be removed from the substrate.

In principle, mixtures 1 and 2 can be applied using any of methods 1 to 3.

Furthermore show:

Figure 1: Photograph of two membranes according to the invention. FIG. 2: Diagram showing the flexibility of membranes according to the invention.

FIG. 3: SEM recordings for the degradation of membranes according to the invention. Figure 4: Degradation profiles of different membranes.

FIG. 5: SEM recordings of surfaces of membranes according to the invention.

FIG. 1 shows fiber-reinforced membranes cut from a DIN A4 sheet and which have already been peeled off from the substrate. These are membranes which were produced according to Example 1 (2-R) and Example 2 (5-R). The fiber-reinforced membrane is intrinsically stable, flexible and has a homogeneous structure.

FIG. 2 shows a diagram from which it can be seen that the flexibility of the membranes produced according to the invention improves with an increasing proportion of organic polymer in the hybrid polymer layer. If twice or five times the mass of organic polymer is used in the manufacturing process based on the inorganic sol, the resulting membrane remains intact even after repeated bending with a small bending diameter. If the mass ratio of organic polymer to inorganic sol in the hybrid polymer layer is only 1: 1, about 75-90% of all membranes break after 10 bending times with a bending diameter of 14 mm. The test results which are shown in FIG. 2 relate exclusively to the fiber-reinforced, biodegradable membranes according to the invention. Membranes that are not fiber-reinforced cannot be handled. They break so easily that no bending tests could be carried out.

FIG. 3 shows three SEM recordings a), b) and c) of a membrane which was produced according to Example 1 and was then wetted with a physiological solution. In FIG. 3 a, which shows a non-degraded film, the film surface is still very homogeneous. After 7 days, the film surface gradually dissolves so that the integrated fibers are exposed (cf. photo in FIG. 3 b). After 64 days, the fibers are detached from the membrane (cf. photo in FIG. 3 c). The membrane has not contracted, but has retained its original shape. However, the degradation of the membrane continues even after 64 days (not shown). FIG. 4 shows degradation profiles of various inventive membranes in phosphate-buffered saline solution over a period of 64 days. The square measuring points stand for a membrane that was produced according to Example 1. The triangular measuring points have been established for a membrane that was produced according to Example 2. The pentagonal and hexagonal measuring points conceal the degradation data of the membranes that were produced according to method 2 with mixtures 1 and 2, respectively.

FIG. 5 shows SEM recordings of surfaces of two membranes according to the invention. They are largely transparent to visible light and have a smooth surface structure.

Claims

1. A method for producing a biodegradable membrane based on an organic-inorganic hybrid polymer comprising: a) producing an inorganic sol by stirring a solution containing it

at least one aqueous solvent, an alkoxysilane and an acid

at a temperature of at least 20 ° C; b) converting the sol to a polymer-sol mixture by adding an end-group-functionalized, biodegradable organic polymer or by adding precursors of the polymer to the sol; and c) applying the polymer-sol mixture to a front side of a foil for curing the mixture to form a hybrid polymer layer, with a multiplicity of fibers being introduced into the mixture in an additional step d) before the mixture is cured.

2. The method according to claim 1, characterized in that the multitude of fibers in step d) i. by distributing fibers on the front of the film prior to applying the mixture, or ii. are introduced into the mixture by distributing the fibers on a surface of the applied mixture, the fibers preferably being aligned along a preferred direction or arranged in the form of a regular scrim or fabric. 3. The method according to any one of the preceding claims, characterized in that steps c) and d) are carried out several times and in each case alternately one after the other.

4. The method according to any one of the preceding claims, characterized in that the solution in step a) is stirred at a temperature of 20 to 50 ° C, preferably from 30 to 45 ° C, particularly before given for a period of at least 7 hours , very particularly before given at least 8 hours, in particular at least 18 hours.

5. The method according to any one of the preceding claims, characterized in that the polymer-sol mixture between step b) and step c) for a duration of 0.5 minutes to 45 minutes, preferably from 1 to 30 minutes, particularly preferably from 5 to 20 minutes, is stirred, in particular at a temperature of 30 to 45 ° C.

6. The method according to any one of the preceding claims, characterized in that the mixture is applied in step c) by squeegeeing or fluxing the front side of the film, the squeegeeing preferably taking place with the aid of a squeegee, a spiral or a film drawing device.

7. The method according to any one of the preceding claims, characterized in that the alkoxysilane is selected from the group consisting of tetramethyl orthosilicate, tetraethyl orthosilicate,

Tetrapropyl orthosilicate, tetraisopropyl orthosilicate,

Tetrabutyl orthosilicate and mixtures thereof.

Method according to one of the preceding claims, characterized in that the end-group-functionalized, biodegradable organic polymer is selected from the group consisting of end-group-functionalized polyesters, end-group-functionalized polyalcohols, end-group-functionalized polyoxazolines, end-group-functionalized polyanhydrides, end-group-functionalized polysaccharides

Polyhydroxylalkanoates, end-group functionalized proteins and Mixtures thereof, the end group functionalization preferably in terminal hydroxyl groups, carboxylic acid groups,

Thiol groups, amine groups, epoxy groups and / or

Trialkoxysilane groups, particularly preferably in terminal hydroxyl groups.

9. The method according to any one of the preceding claims, characterized in that the acid is a sulfonic acid, preferably

Methanesulfonic acid, and / or a mineral acid, preferably HCl, H ₂ S0 ₄ , HN0 ₃ , Hl, H3PO4, and / or the solution in step a) has a pH between 1 and 7, preferably between 1 and S, has .

10. The method according to any one of the preceding claims, characterized in that the aqueous solvent is water or a mixture of water and an alcohol, tetrahydrofuran or toluene, preferably a mixture of water and an alcohol, e.g. Ethanol.

11. The method according to any one of the preceding claims, characterized in that the polymer in step b) in a weight ratio of 0.1 to 10.0, preferably from 0.5 to 8.0, in particular from 1.0 to 6 , 0, is added to the inorganic sol.

12. The method according to any one of the preceding claims, characterized in that the fibers from the group consisting of silica gel fibers, Ti0 ₂ -containing fibers, polyester fibers, polyanhydride fibers, polysaccharide fibers, polyhydroxyalkanoate fibers, protein fibers and mixtures thereof, preferably from the group consisting of Silica gel fibers and Ti0 ₂ -containing fibers are selected, the fibers particularly preferably in a proportion of at most 50% by weight, very particularly preferably at most 33% by weight, in particular at most

25% by weight, based on the total mass of hybrid polymer layer and fibers, can be used. 13. The method according to any one of the preceding claims, characterized in that the fibers have a diameter of 1 nm to 2 mm, preferably from 1 to 100 miti.

14. The method according to any one of the preceding claims, characterized in that the membrane is detached from the front side of the film after a drying time of at least 30 minutes, the front side of the film is preferably adhesive and / or consists of ethylene-tetrafluoroethylene copolymer .

15. The method according to any one of the preceding claims, characterized in that at least one pharmacologically active compound is added in step a) or b) or is used after curing to impregnate the hybrid polymer layer, the proportion of the pharmacologically active compound being selected so that it is preferably from 1 to 20% by weight based on the total mass of hybrid polymer layer and fibers.

16. A membrane containing or consisting of a biodegradable organic-inorganic hybrid polymer and a large number of fibers.

17. Membrane according to claim 16, characterized in that the

The membrane is decomposed and / or degraded by contacting it with a physiological solution, preferably an aqueous PBS solution containing NaCl, KCl, Na ₂ HP0 ₄ and KH ₂ P0 ₄ .

18. Membrane according to claim 17, characterized in that the

Membrane after 8 days of contact with the aqueous PBS solution at least 10% by weight of the total mass, preferably at least 20% by weight of the total mass, particularly preferably at least

25 wt .-% of the total mass, is decomposed and / or degraded.

19. Membrane according to one of claims 16 to 18, characterized in that the membrane forms a barrier for the growth of human or animal cells over a period of at least three days, preferably 5 days, particularly preferably 7 days. 20. Membrane produced by a method according to claims 1-15.

21. Membrane according to one of claims 16 to 20 for use in surgical interventions in which there is a risk of postoperative formation of adhesions or scarring, especially when inserting prostheses and implants, or in pharmaceutical processes as active ingredient carriers.