DE102012224379A1 - Fiber product useful in medicine, preferably surgery comprises fibers comprising modified starch - Google Patents

Abstract

Fiber product comprises fibers comprising modified starch. The fibers are prepared using rotary spinning. An independent claim is also included for producing the fiber product, comprising producing the fibers from a fiber raw material comprising modified starch by means of rotational spinning.

Description

The invention relates to a fiber product having fibers which have modified starch, and to a production process for the fiber product.

Nonwovens or fiber corrugations with rotationally spun gelatin fibers and their use for wound healing or wound covering are from the documents WO 2008/107126 A1 and WO 2009/036958 A2 known.

From the WO 2012/022422 A1 Nonwovens with hydroxypropyl cellulose fibers are known, inter alia, for wound care or as a wound dressing.

From the US 2007/0087061 A1 For example, a wound sealant with microporous particles of epichlorohydrin-crosslinked starch is known.

Furthermore, from the WO 2009/091549 A1 the use of modified starch for hemostasis known.

Body hygiene articles with melt-spun composite starch fibers go out of the US 2012/0216709 A1 out.

In general, the following product categories are used for tissue sealing:
The first category concerns sealants based on polysaccharides. The products of this category have in common the ability to absorb a large amount of fluid within a very short period of time and to accelerate blood clotting by concentrating platelets. This fluid uptake relies on capillary forces emanating from loosely-formed, three-dimensional polymer networks in which repulsively charged functional groups (for example, carboxylate or phosphate groups) repel each other and act on the physiological fluids. Examples of such sealing means are for example the products commercially available under the names Surgicel ^® and TachoComb ^®, which have a porous implant structure, composed of oxidized cellulose and are degraded within two months in the body. A further example is sold under the name ChitoFlex ^® are available commercially, consisting of chitosan, as well as the commercially available under the designation Perclot ^®, made up of carboxymethyl starch, absorbent powder. The commercially available under the name Arista ^® AH product is a Powder of epichlorohydrin-modified amylose.

The second category of sealants affects collagen products such as those sold under the names Spongostan ^® (porcine gelatin), Lyostypt ^® (bovine collagen) and DuraGen ^® (bovine collagen) available products. The second category sealants act in a similar way to the first category sealants, but are additionally being discussed for stimulating the intrinsic coagulation cascade by activating Factor XIIa. The sealants of the second category are not completely absorbed. Rather, they are only integrated into the surrounding tissue, so that a distinction between product material and the body's own tissue after four to six months is usually no longer possible.

The third category consists of liquid sealants, which are mostly based on synthetic polymers. Examples are hydrogels based on PEG derivatives that are commercially available under the names CoSeal ^®, ProGel ^®, DuraSeal ^®, Floseal ^{®, ®} and Focalseal Bioglue ^®. The sealants of this category are generally available as hydrogels. Upon contact with blood, the sealants experience a significant increase in volume. The concomitant compression on blood vessels finally causes haemostasis.

The last category of sealants are the fibrin sealants. In contrast to the sealants of the categories described so far, they actively intervene in the coagulation cascade and are based on an interaction of the components fibrin, thrombin and aprotinin, which causes blood coagulation. Corresponding products are commercially available under the names Evicel ^®, Tissucol ^{®, ®} and Quixil Beriplast ^®.

Although satisfactory results can be obtained with the known fabric sealants in most cases, problems may arise in individual cases.

Thus, with oxidized cellulose sealants, the occasional occurrence of infection and tissue irritation as well as the formation of acid degradation products can be problematic and detrimental to biocompatibility. Another disadvantage is the generally very complex and particularly environmentally harmful production process, in which a cellulose fleece is treated with highly toxic, carcinogenic nitrogen dioxide. Even the slightest deviations in the production process can lead to overoxidation and thus to a complete loss of mechanical stability or, in the case of underoxidation, to a reduced biodegradability, since cellulose is poorly biodegradable due to the absence of an endogenous β-amylase.

Chitosan-based sealants have the fundamental disadvantage that chitosan must be extracted from the shellfish shell, making the manufacturing process expensive. Furthermore, chitosan is usually degradable in the body only up to a molecular weight of about 20 kDa. Higher molecular weights can be degraded mainly due to the presence of β-1,4-glycosidic linkages only by special microbial enzymes.

Powdered hemostyptics may be disadvantageous in that they can be flushed away from a situs in the early stage of an application in particular heavy bleeding due to the lack of a closed Hämostyptikaschicht. Also, a compression of blood vessels alone by the use of powders is not possible, which in particular with heavy bleeding additional aids such as compresses must be used.

Collagen products generally must be subjected to expensive purification procedures as well as methods for detecting complete virus and prion deactivation. Furthermore, these products are subject to the inherent risk of protein-based allergies. In addition, calcifications may sometimes occur at the interfaces to collagen implants. Although these disadvantages can be circumvented in the case of the use of equine collagens. However, collagene of equine origin are significantly more expensive than bovine collagens.

Liquid fabric sealants must be prepared in complex and complicated syntheses, whereby their production is very expensive overall. Most liquid sealants must also be stored refrigerated and discharged through multi-chamber systems, resulting in additional operations and sources of error for a surgeon, as well as a greater amount of time. In addition, most sealants have only a low tear resistance after they have cured.

Fibrin adhesives are also expensive sealants because they are usually made using specially validated methods from human blood to rule out human-associated infectious diseases such as AIDS, Hepatitis C or Creutzfeldt-Jakob. Fibrin sealants are also discharged by means of multi-chamber systems and therefore have the same extent as described in the preceding paragraph disadvantages. In addition, the durability of fibrin adhesives is severely limited. Finally, because of their active intervention in metabolism, fibrin sealants in the European Union are currently medicinal products rather than medical devices, resulting in higher licensing costs.

Task and solution

Against this background, the object of the present invention was to provide a product which circumvents disadvantages known from the prior art and, due to its nature, makes possible, in particular, a multifunctional use in the field of medicine.

This object is achieved in a first aspect of the invention by a fiber product having the features of independent claim 1. In a second aspect, the invention relates to a manufacturing method for the fibrous product having the features of independent claim 17. Preferred embodiments of the fibrous product and method are defined in dependent claims 2 to 16 and 18 to 20. The wording of all claims is hereby incorporated by express reference into the content of the present specification.

The first aspect of the invention relates to a fiber product, preferably a medical fiber product, i. a fiber product intended for use in medicine, in particular surgery.

The fiber product comprises fibers having modified starch.

The fiber product is characterized in particular by the fact that the fibers are produced or producible by means of rotary spinning or a rotary spinning process.

The invention is based on the surprising finding that fiber products, preferably in the form of nonwovens or nonwovens, having modified starch fibers can be produced by means of rotary spiders, which are particularly advantageous due to a strong and especially rapid suction and / or swelling capacity, due to high mechanical strengths, after swelling due to membrane-like properties (ie, they are present after swelling as a membrane or a kind of membrane) and characterized by a complete absorption capacity. As a result, fiber products according to the invention can be used multifunctionally in medicine. Of particular advantage here is the excellent biocompatibility of modified starch. For example, allergies to starch are extremely rare. On top of that, modified starch can be rapidly degraded due to the ubiquitous presence of amylase in the human or animal body. The properties described above are particularly advantageous from the viewpoint of achieving rapid primary wound healing.

Furthermore, it was surprisingly found that spin-spun modified starch fibers are characterized by a higher swelling capacity and in particular higher strengths than the known from the prior art rotationally spun gelatin fibers.

Furthermore, the rotary spinning process offers a wealth of parameters to specifically influence the nature of the fibers and thus the properties of the fiber product. Thus, for example, by fixing the rotational speed, a possible material and / or air gradient, the hole size in the bottom of the rotary container (spinning rotor) as well as determining any electric field, a larger bandwidth to realize fiber diameter than is the case for example in the conventional melt spinning process ,

Another advantage is that the rotation spinning process can be controlled relatively easily and always reproducible production conditions due to the physical laws of the responsible for fiber formation centripetal forces, which also in realization of larger production scales (so-called upscaling) by using larger containers (spinning rotors) readily let adjust.

Finally, the fiber product of the present invention, as well as the process for its preparation, alone because of the excellent handling properties, add commercial value over generic products and processes.

The term "modified starch" in the sense of the invention can not only be a modified type of starch (singular), but also a plurality, in particular a mixture, i. mean two or more different, modified types of starch.

In addition, from the term "modified starch" within the meaning of the present invention, not only neutral modified starches, i. modified starches which have no salt charges, but also salts, for example alkali or alkaline earth salts, modified starches may be included.

The modified starch in a preferred embodiment is selected from the group comprising physically modified starch, chemically modified starch, pregelatinized starch, pregelatinized starch, enzymatically modified starch, naturally modified starch, and mixtures thereof.

In a further embodiment, the modified starch is a physically modified starch selected from the group comprising radiation modified (i.e., radiation modified) starch, mechanically modified starch, water vapor modified starch, and mixtures thereof.

The physically modified starch mentioned in the previous paragraph may, for example, be selected from the group comprising γ-irradiation modified starch, UV irradiation modified starch, plasma modified starch, ethylene oxide sterilized starch, starch modified by ozone sterilization starch modified by formaldehyde sterilization and mixtures thereof.

In another embodiment, the modified starch is a pregelatinized starch by spray drying.

In another embodiment, the modified starch is a pregelatinized starch having variable proportions of amylose and amylopectin. A suitable pregelatinized starch may have levels of amylose and amylopectin in the ratio 0.1: 99.9 to 99.9: 0.1.

In a further embodiment, the modified starch may be a naturally modified starch selected from the group comprising microbiologically modified starch, recombinantly modified starch and mixtures thereof.

In another embodiment, the modified starch is a chemically modified starch selected from the group comprising acid modified starch, alkali or base modified starch, bleached starch, oxidized or oxidatively degraded starch, esterified starch (alcohol groups of the starch are at least partially esterified etherified starch (alcohol groups of the starch are at least partially alkylated and / or arylated), crosslinked starch, hydrophilized, in particular carboxylated and / or hydroxylated, starch, acetylated starch, phosphorylated starch, grafted starch and mixtures thereof.

A suitable chemically modified starch is, for example, a starch crosslinked by means of a polybasic carboxylic acid such as, for example, citric acid and / or a starch crosslinked by means of epichlorohydrin. Starches of this type are distinguished, in particular, by ester- and / or ether-flanked bridges.

In a further embodiment, the modified starch is selected from the group comprising acid-treated starch (approved as a food additive under No. E 1401), alkaline-treated starch (permitted as a food additive under No. E 1402), Bleached starch (permitted as a food additive under No. E 1403), oxidized starch, in particular oxidatively degraded starch (authorized as a food additive under No. E 1404), enzymatically modified starch (permitted as a food additive under No. E 1405), monostarch phosphate ( permitted as a food additive under No. E 1410), distarch phosphate (permitted as a food additive under No. E 1412), phosphated distarch phosphate (approved as a food additive under No. E 1413), acetylated distarch phosphate (approved as a food additive under No. E1414 ), acetylated starch ( authorized as food additives under Nos. E 1420 and E 1421), acetylated distarch adipate (authorized as a food additive under No. E 1422), acetylated distarch glycerol (permitted as a food additive under No. E 1423), distarch glycerin (as a food additive under no. E 1430), hydroxyethyl starch, hydroxypropyl starch (approved as a food additive under No. E 1440), hydroxypropyldistarch glycerin (approved as a food additive under No. E 1441), hydroxypropyldistarch phosphate (as a food additive under No. E 1442), starch sodium octenylsuccinate (in the form emulsifying starch as a food additive under the designation E 1450), acetylated oxidized starch (approved as a food additive under No. E 1451), cationic starch, anionic starch, sodium starch glycolate, especially of types A, B and / or C, acrylated starch, crosslinked strengthening e and mixtures thereof.

Sodium starch glycolate Type C has the advantage that corresponding fibers are present in a highly viscous state after swelling, so that the fibers can not be flushed out or collapsed from a situs, which is particularly advantageous in heavily bleeding body defect areas, especially situs. In addition, sodium starch glycolate can be prepared starting from monochloroacetic acid and native starch and therefore waiving toxic reagents.

According to the invention, in another embodiment, the fibers may comprise any mixture of the modified types of starch described in the preceding embodiments.

The fibers of the fiber product may each have a proportion of the modified starch of from 50% by weight to 99% by weight, in particular from 65% by weight to 95% by weight, preferably from 65% by weight to 75% by weight. , based on the total weight of a single fiber. By varying the modified starch content, properties of the fiber product such as, for example, its tensile strength and absorbency or swelling capacity can be set in a particularly advantageous manner.

To improve or increase the flexibility of the fibers, these may each further comprise a plasticizer.

The plasticizer may be selected from the group comprising sugar alcohols, alcohols, polyalcohols, polyethers, sodium cellulose glycolate, polyvinyl acetate, polyvinylpyrrolidine and mixtures thereof.

Suitable alcohols or polyalcohols as plasticizers may be selected from the group comprising mannitol, sorbitol, ethanol, glycerol, polyvinyl alcohol and combinations thereof. Examples of suitable polyethers are polyethylene glycols and / or polyethylene oxides.

A preferred plasticizer is glycerine.

The fibers of the fiber product may each have a proportion of the plasticizer of 1 wt .-% to 50 wt .-%, in particular 5 wt .-% to 40 wt .-%, preferably 20 wt .-% to 35 wt .-%, based on the total weight of a single fiber.

In a further embodiment, the fibers of the fiber product furthermore each have a filler or structuring agent. The filler or structurant in particular has the function of stabilizing or compressing the fiber product in its shape.

Suitable fillers or structuring agents are in particular polysaccharides and / or water-swellable synthetic polymers. For example, the filler or structuring agent from the group comprising crosslinked and especially low molecular weight polyvinyl alcohol, crosslinked polyvinyl acetate, crosslinked polyvinylpyrrolidone (eg commercially available under the name Polyplasdone ^TM ), polyvinyl ureas, dextranes, sodium cellulose, glycolate, Crosscaramellose (for example, under the name Ac-Die -Sol ^™ commercially available), hydroxyalkylcelluloses such as hydroxypropylmethylcellulose, hydroxyalkylcelluloses such as hydroxypropylmethylcellulose, hydroalkylcelluloses such as hydroxyethylcellulose, alkylcelluloses such as methylcellulose, microcellulose (for example, commercially available under the name Avicel ^™ ), pectin, gellan, alginates, ion exchangers, for example based on of methacrylate copolymer with divinylbenzene (eg commercially available under the name Tulsion ^™ from Thermax), salts thereof and mixtures thereof and mixtures thereof. Particularly preferred are gellan, alginate, salts, in particular sodium alginate, and / or sodium cellulose glycolate.

The fibers of the fiber product can each have a proportion of the filler or structuring agent of 0 wt .-% to 10 wt .-%, in particular 0.1 wt .-% to 5 wt .-%, preferably 1 wt .-% to 5 wt. %, based on the total weight of a single fiber.

In a further embodiment, the fibers of the fiber product consist of modified starch and optionally additives, in particular selected from the group comprising plasticizers, fillers or structurants, pharmaceutical or medicinal active ingredients and mixtures thereof. With regard to further features and advantages, to avoid unnecessary repetition, reference is made in full to the previous description.

In another embodiment, (at least) some fibers of the fiber product are randomly entangled or twisted together. These entanglements or twists increase the mechanical strength of the fiber product with particular advantage. On top of that, the entanglements or twists of individual fibers can combine them into fiber bundles, which can be displaced reversibly relative to one another. On the one hand, this additionally increases the mechanical strength of the fiber product. On the other hand, it is possible to non-destructively stretch the fiber product.

In a further embodiment, the fiber product may have areas where the fibers merge without phase boundaries. In other words, two or more fibers can form a joint where no phase boundary is seen and the fibers are in principle fused together. Such areas increase the bond between the fibers and, overall, the compactness of the fiber product.

In a further embodiment, the fiber product has sides, preferably opposite sides, with different fiber structure. The sides are preferably surface areas of the fiber product.

For example, the fiber product can have a first side, preferably a first surface side, with regions where two or more fibers without phase boundary merge into one another, and a second and especially opposite side, preferably a second and especially opposite surface side, without such regions, ie exclusively individualizable individual fibers. With special The advantage here is that the second side can be provided to rest on a body defect area to be treated, such as, for example, a wound area.

The fibers may have a diameter in the nano and / or micro range.

For example, the fibers may have a diameter of 50 nm to 200 .mu.m, in particular 1 .mu.m to 150 .mu.m, preferably 5 .mu.m to 100 .mu.m (determined by means of scanning electron microscopy as the mean value of 50 individual fibers).

The fiber product may furthermore have a thickness of 0.1 mm to 10 mm, in particular 0.2 mm to 6 mm, preferably 0.5 mm to 3 mm (determined according to ISO 9073-2 ).

The fibrous product is preferably open-porous in a further embodiment in the dry state.

In particular, the fiber product in the dry state, an open pore structure with an air permeability of 0.1 l / [min cm ² ] to 1 l / [min cm ² ], in particular 0.3 l / [min cm ² ] to 0.8 l / [min cm ² ] , preferably 0.3 l / [min cm ² ] to 0.7 l / [min cm ² ], (determined by EN ISO 9237 ).

In a particularly advantageous embodiment, the fibrous product is swellable in the dry state on contact with water or aqueous liquids, in particular body fluids such as, for example, blood, exudate, liquor and / or lymph. The swellability or the swelling capacity of the fiber product is attributable, in particular, to the large number of polar functional groups with a very high water absorption or binding capacity contained in the starch. Depending on the starch modifications, the swelling capacity of the fibers and thus of the fiber product can be controlled in a targeted manner.

Pores of the fiber product are preferably closed as a result of the swelling process, whereby the fiber product with particular advantage air and / or liquid-sealing and mechanically strong, in particular membrane-like properties receives. In addition, by such pore closure, the risk that pathogens are introduced into a treated body defect area can be minimized.

The fiber product may, for example, have a liquid absorbency, in particular a water and / or body fluid absorbency, which corresponds to 1 to 35 times, in particular 8 to 30 times, its dry weight. With particular advantage, the fiber product exhibits a corresponding pumping speed within a period of 0.01 s to 900 s, in particular 0.1 s to 300 s, preferably 1 s to 100 s, after contact with the liquid, in particular water and / or the body fluid. As a result of its high and in particular rapid pumping speed, the fiber product is able, for example, to reduce blood volumes rapidly and to ensure rapid and reliable wound closure via an equally rapid concentration of platelets. On top of that, reducing blood volume improves the surgeon's view of the body defect area to be treated.

In a further embodiment, the fibrous product in the moist or swollen state can have an elongation of 50% to 400%, in particular 100% to 300%, preferably 150% to 200%, based on its original length (in the unstretched state). This makes it possible, for example, to select the fiber product in a size which corresponds to the size of a body defect area to be treated. Upon contact with body fluid, the fiber product then expands over the defect edges, so that as a result an overlapping defect treatment is possible, without having to work from the outset with a fiber product oversized with respect to the defect size. In this way you can effectively save foreign material.

In a particularly advantageous embodiment, the fibrous product is mechanically compacted or solidified in the dry state. As a result, an additional increase in the impermeability to air and / or liquids, in particular body fluids, as well as the mechanical strength of the fiber product can be achieved.

The fiber product may be mechanically compacted or solidified by mechanical techniques such as by water jet needling and / or pressing, in particular by means of a punch or calender.

The fibrous product in the dry state preferably has a tensile strength of at least 0.15 N / mm ² , in particular from 0.15 N / mm ² to 3 N / mm ² , preferably 0.5 N / mm ² to 2 N / mm ² , more preferably 1 N / mm ² , on (determined after ISO 9073-3 ).

In a further embodiment, the fibers are deposited using a gradient of material, in particular with respect to the modified starch.

In a preferred embodiment, the fiber product comprises fibers or fiber fractions with different modified starch content.

In particular, the fiber product may have two or more layers comprising fibers or fiber fractions with different modified starch content.

The fibers or fiber fractions mentioned in the two preceding embodiments preferably form a gradient in the fiber product with respect to their modified starch content.

Preferably, the gradient extends from one surface side of the fiber product to another, preferably opposite, surface side of the fiber product. The gradient particularly preferably extends over the thickness of the fiber product. The modified starch portion may follow a continuous or discontinuous, in particular stepped, running gradient.

In particular, the fibrous product may comprise a first layer having fibers or fiber fractions having a first modified starch portion and a second layer having fibers or fiber fractions having a second modified starch portion, the second modified starch portion being smaller or larger, preferably smaller, than the first modified starch portion. According to the invention, it is advantageous if the second layer is intended to rest on a body defect area to be treated, in particular a wound area. Although a smaller modified starch content lowers the tensile strength of the fiber product, it increases its absorbency.

The fibrous product is preferably resorbable in vivo within a period of 4 weeks.

In a further embodiment, the fiber product is designed as a surface image. In a particular embodiment, the fiber product is designed as a three-dimensional sheet.

The fabric may further be a textile or non-textile or non-woven fabric.

The fiber product may in particular be selected from the group comprising nonwoven or nonwoven fabric, scrim, knitted fabric, knitted fabric, fabric and thread.

In a particularly preferred embodiment, the fiber product according to the invention is a nonwoven or a nonwoven fabric.

Furthermore, it is particularly preferred if the fiber product is a medical implant or the fiber product is intended for use as a medical implant.

The fiber product can generally be used as an absorbent for body fluids, especially blood, exudate, pus, cerebrospinal fluid and / or lymph.

Preferably, the fibrous product is a hemostatic, i. for hemostasis, suitable.

In particular, the fiber product can be used to stop heavy bleeding, in particular from bleeding of parenchymatous organs (lung, kidney, spleen and liver).

Furthermore, the fiber product can be provided for sealing tissue and / or wounds, in particular internal wounds.

In particular, the fiber product is suitable for approximating tissue halves which have been separated from one another, for example as a result of surgery.

Another application of the fiber product relates to its utility as an anti-adhesion agent, ie as an agent for the prevention and / or prophylaxis of post-surgical or postoperative tissue adhesions.

Furthermore, the fiber product may be for use in sealing liquid and / or gas leaks in the body of a human or animal patient. The fluid leaks may be, in particular, blood, exudate, purulent, cerebrospinal fluid and / or lymphatic leaks. The gas leaks are typically air leaks.

Another application of the fiber product relates to its usability as an adhesion and / or germ barrier.

Further applications relate to the usability of the fiber product as a wound bridge for the prevention of wound dehiscences, to cover a dura defect, as a fascia replacement, as cavernosa for vascular compression and / or tissue overlap and / or as a placeholder for the body's own tissue.

In a second aspect, the invention relates to a method for producing a fiber product, in particular such as has been described in the context of the first aspect of the invention.

The method is characterized in particular by the fact that, starting from a fiber raw material which has modified starch, fibers are produced by means of rotary spinning or a rotary spinning process.

The fiber raw material is expediently in fluid or fluidized form.

For example, the fiber raw material may be provided in the form of a melt, solution, suspension or dispersion.

The fiber raw material may, in addition to the modified starch optionally have at least one additive, in particular selected from the group comprising plasticizers, structuring agents or fillers and mixtures thereof.

The fiber raw material may have a modified starch content of from 50% to 99%, more preferably from 65% to 95%, preferably from 65% to 75%, by weight on the total weight of the fiber raw material.

Furthermore, the fiber raw material may have a plasticizer content of 1 wt .-% to 50 wt .-%, in particular 5 wt .-% to 40 wt .-%, preferably 20 wt .-% to 35 wt .-%, based on the Total weight of fiber raw material.

Furthermore, the fiber raw material may have a proportion of a filler or structuring agent of 0 wt .-% to 10 wt .-%, in particular 0.1 wt .-% to 5 wt .-%, preferably 1 wt .-% to 5 wt .-% , based on the total weight of the fiber raw material.

In a preferred embodiment, the fiber raw material for producing the fibers is placed in a container, wherein the container is set in rotation and wherein the fiber raw material is discharged by Zentripetalkräfte from the container in the form of fibers.

The exiting fibers can be directed, guided without contact. A contactless and defined guidance of the fibers, before these impinge on a depositing device, allows with particular advantage a modification of the fibers. Thus, the duration of the guidance or the direction of the guidance alone can influence the fiber length, the fiber diameter and the fiber structure. A directional non-contact guide produces a more homogeneous fiber spectrum than a non-guided manufacturing process. Concretely, the width of a distribution curve of all fiber properties can be adjusted solely by the guidance. As a result, the amount of fibers with undesirable fiber geometry can be significantly reduced.

In a further embodiment, the fibers are discharged from the container via exit regions which are preferably designed as passages. The exit regions may have a diameter of 0.1 mm to 2 mm, preferably 0.3 mm to 1 mm, more preferably 0.3 mm to 0.7 mm.

Furthermore, the outlet areas of the container may have a mutual distance of 10 mm.

In an advantageous embodiment, the container is heated to a temperature of 90 ° C to 180 ° C, in particular 140 ° C to 180 ° C, preferably 150 ° C to 170 ° C, more preferably to 160 ° C.

The container can be rotated at a speed of 1 rpm to 25,000 rpm, in particular 2,000 rpm to 10,000 rpm, preferably 3,000 rpm to 7,000 rpm.

The container mentioned in the preceding embodiments is generally a so-called spinning rotor.

In a particularly advantageous embodiment, the fibers may be passed through a suction device. As a result, further stretching or twisting of the fibers and thus an increase in the individual fiber strength can be achieved. According to the invention, it is conceivable that the fibers are transported by a gas stream. As a gas, for example, air can be used. Alternatively or in combination with air, however, inert gases such as nitrogen may also be used.

In another embodiment, the gas stream may be changed, in particular gradually changed, during the spinning process. In this way, different fiber structures can be realized in the fiber product. For example, a gradual reduction of the gas flow leads to the formation of regions with individualizable fibers and to the formation of regions where the fibers merge without phase transitions

In order to form fibers with different modified starch content, in particular for forming a gradient with respect to the modified starch content in the fibers, it may be preferred according to the invention to change, in particular gradually change, the proportion of the modified starch in the fiber raw material during rotary spinning. The gradual change can follow a continuous or discontinuous, in particular stepped, gradient. The embodiments described in this section can be realized, for example, by feeding the rotary container described in the preceding embodiments with different conveying rates with a first modified fiber raw material and with a second fiber raw material containing only additives such as plasticizer and / or filler. For example, the first fiber raw material can be fed to the rotary container at a constant delivery rate, while the second fiber raw material is supplied to the rotary container at a continuously increasing delivery rate.

The fibers are collected in a further embodiment on a storage device.

Preferably, the fibers are deposited using a gradient of material, especially with respect to the modified starch.

The fiber production can be supported in other embodiments by applying an electric field, for example between a storage device and the container.

In a particularly advantageous embodiment, the spin-spun fibers are mechanically compacted or solidified. This can be done for example by means of water jet needling and / or pressing, in particular under a pressure of at least 50 N / mm ² . The pressing of the fibers can continue to be done with the aid of a sand punch or a calender.

With regard to further features and advantages of the method, in order to avoid unnecessary repetitions, reference is made in full to the statements made in the context of the first aspect of the invention in connection with the fiber product.

Further features and advantages of the present invention will become apparent from the following description of preferred embodiments in the form of examples and the dependent claims. The preferred embodiments are merely for the better understanding of the invention, without limiting it thereto.

example part

Example 1:

In a rotary spinning head, a liquid melt of seven parts of sodium starch glycolate type C (Viva Star P5E, M _w > 15 kDa from JRS PHARMA) and three parts of glycerol (PZN 7474853 from A. Hedinger GmbH & Co. KG) and 0.3 parts Sodium alginate (Item No. A 2033-100g from Sigma-Aldrich) at a temperature of 160 ° C and a rotational speed of 4,500 rev / min through holes with a diameter of 300 microns in the container bottom expressed. The formed nonwoven fabric was additionally pressed by means of a calender from Sumet at a pressure of 50 N / mm ² at a throughput speed of 5 m / min. The fibers had an average diameter of about 100 microns and had a tensile strength of 0.5 N / mm ² . The produced nonwoven absorbed 20 times its own weight in water.

Example 2:

Another fleece was prepared according to the procedure of Example 1, but with the difference that instead of the sodium starch glycolate of type C, distarch phosphate (special starch 6039 G from Südstärke GmbH) was used. The nonwoven exhibited a water absorption capacity which was 15 times its own weight.

Examples 3 to 5:

Additional nonwovens were prepared according to the procedure of Example 1, the following modified starches being used instead of sodium starch glycolate of type C: acetylated distarch phosphate (special starch 6345 CG from Südstärke GmbH), cationic starch (Catiosol 9 SSG from Südstärke GmbH), sodium starch glycolate type A (Ultramyl ^®, Item No. 131212 of the firm Parmentier GmbH), which is used as a tablet disintegrant in the pharmaceutical industry.

Example 6:

It was another non-woven according to the experimental procedure of Example 1 using, instead of the sodium alginate, gellan (Phytagel ^™, Cat P8169-500g Sigma-Aldrich) was used. The absorbency of the web produced corresponded approximately to the absorbency of the web produced according to Example 1. However, the wetting time increased from 10 seconds to over 5 minutes. In other words, with gellan as a nonwoven material, rapid wettability thereof could not be realized.

Example 7:

In an animal model, nine rabbits of the white Russian strain were divided into three groups. One group was a positive control using the commercially available under the name ^® Lyostypt collagen sponge, a second group with the product prepared according to Example 1 and nonwoven according to the invention the third group as a negative control (with pure Zulkowskystärke No. 85642-100g Sigma-Aldrich ) for the purpose of hemostasis.

For this purpose, the rabbits were subjected to anesthesia, analgesia and a muscle relaxant, and then, after median laparotomy, the liver was placed in front of them and then a 1 cm wide and 0.3 cm deep defect was set with an electric scalpel. Immediately thereafter, the three products were administered as hemostyptic in three groups of three animals each.

In the case of Zulkowskystärke addition a cotton ball had to be used for compression to prevent flushing of the starch.

In the groups with collagen sponge and the web according to the invention, haemostasis was achieved within 180 seconds after pressing on the corresponding hemostyptic.

In the negative control, no complete hemostasis was observed after 180 seconds of compression on the wound.

All products were then left in the animals. The abdomen was closed in layers by means of continuous suture rows and final intracutaneous seam and bonding with Histoacryl ^®.

In the case of the nonwoven according to the invention (prepared according to Example 1), a section performed after four weeks showed that no postoperative adhesions to the peritoneum or to other adjacent organs occurred. A simple potassium iodide iodine detection also showed that no modified starch was left (lack of blue color). In an in vitro laboratory experiment, however, sodium starch glycolate showed a pronounced blue color after contact with the potassium iodide-iodine solution. The modified starch used was thus completely absorbed.

Example 8:

Pork livers were organized by the local slaughterhouse. With the help of a ventilator, a pressure of 60 mbar was set. The trachea of the pork leashes were connected to a trocar corresponding to the diameter, fixed with cable ties and connected to the ventilator's compressed air hose. The lungs were aerated at about 60 mbar for several minutes until all lobes had expanded sufficiently.

A circle of about 2 cm in diameter was cut out of an unventilated lung using an HF scalpel. The lung was then ventilated and the defect measured at 30 mbar. Thereafter, the lung was kept under water to determine the degree of leakage. Then the lungs were taken out of the water and vented. The defect was blotted dry.

The nonwoven fabric was positioned in Example 1 and fixed by means of commercially available under the name ^® Bioglue (Fa. Cryolife), synthetic albumin adhesive to the defect on the wound, leaving only the edge of the defect was sprayed to about 1 cm. The fibrin sealant was allowed to polymerize without load for a period of 3 minutes.

Then the lungs were again ventilated manually until they had expanded sufficiently again. The pressure was adjusted to 30 mbar and the lungs were kept under water to assess the leak. The lung was cycled over a period of 5 minutes at 30 mbar in an automatic mode, and then the adhesion of the film was tested. The degree of leakage of the sealed site was determined in triplicate:
Grade 0: no bubbles
Grade 1: isolated small air bubbles (<2 mm diameter)
Grade 2: "string" of small bubbles (<2 mm diameter)
Grade 3: large air bubbles (> 2 mm diameter)

This resulted in the following result:
Defect not ventilated: 24 × 21 × 5 mm
Defective vented: 34 × 31 × 10 mm
Level of leakage without fleece: 3
Level of leak with fixed fleece after 3 minutes cure time at time t = 0: 0
Degree of leakage after t = 5 min with a load of 30 mbar: 0
Level of leakage after t = 5 min with a load of 30 mbar and an additional short-term peak load of 60 mbar: 0

Example 9:

In a Schweinetierversuch a Duradefekt-coverage was performed with a non-woven fabric prepared according to Example 1. For this purpose, the web was tested in comparison to the commercially available under the name Lyoplant ^® purified and lyophilized bovine pericardium. Following anesthesia, analgesia and the administration of a muscle relaxant, a 6 cm long incision was made temporoparietal in six animals (number of animals per group: three) and bleeding was stopped by conventional techniques. Subsequently, a 4 cm diameter craniectomy was performed to prepare the animal's dura mater. Thereafter, a Duradeefekt was set with a diameter of 2.5 cm. The product Lyoplant ^® was sutured to the defect on the remaining dura mater. In comparison, the fleece was only hung up.

For intraoperative pressure measurement, a craniotomy was performed on the upper skull to determine intracranial pressure using a so-called Codman probe. After the application of the implants to be tested, the impermeability of the implants was checked using the so-called Valsalva maneuver, before the defect was sealed to the bone plate and to the skin closure has been. The craniotomy site was closed by skin closure only. The section of the animals took place after 28 days.

After general anesthesia, analgesia and doping with a muscle relaxant, the dura mater was again freely dissected and macroscopically inspected. The implants of both groups were well-ingrowned and withstood the intracranial pressure of at least 10 kPa applied by Valsalva maneuver.

Example 10:

Cationic starch with a degree of substitution of 0.66 was prepared by a method described in the literature [ Adomačiūtė E, Milašius R, Žemaitaitis A, Bendoraitienė J, Leskovšek M, Demšar A. Fibers & Textiles in Eastern Europe, 2009; 17, 3 (74): 29-33. ]. A 15% strength by weight solution of the cationic starch in water (dynamic viscosity 20 mPa.s at 25 ° C.) was mixed with a 13% strength by weight polyvinyl alcohol solution (Mowiol 20-98, Mw 125 kDa, Sigma-Aldrich) Ratio 3/1 mixed. The mixture was diluted to a solids content of 12% by weight, and 1% by weight of glycerin and 1% by weight of sodium alginate were added. Using an ultrasonic bath (VWR USC 1200D, step 9), the mixture was homogenized for 30 minutes at 30 ° C. The homogenized mixture was then used for fiber spinning. For this purpose, the solution was conveyed by means of a syringe pump (Harvard syringe pump 11) with a speed of 8.6 ml / min into a spinning rotor. The temperature of the spinning rotor was maintained at 90 ° C. The spinning rotor was rotated at 3000 rpm. The fibers were deposited after leaving the spinning rotor (diameter of the spinning openings 0.4 mm) at 23 ° C on a suction below the rotor. The extraction was set to 1000 m ³ / h at the beginning of the spinning process. The spinning process was carried out for 15 minutes, whereby the suction was reduced in 3-minute increments by 100 m ³ / h. This gave a 3 mm thick nonwoven ( ISO 9073-2 ) having a basis weight of 220 g / m ² ( ISO 9073-1 ) whose top was noticeably different from the bottom. While the underside consisted of isolated fibers in the form of a loose fleece, the fibers on the upper side (partially) fused together and formed a dense and particularly compact structure. The resulting nonwoven was post-treated for 4 hours at 120 ° C in a vacuum oven (5 mbar). The fiber diameter was determined by scanning electron microscopy as the mean value of 20 individual fibers and was 15 ± 4 microns. The water absorption of the nonwoven was 15 times its dry own weight. For this purpose, a 10 × 10 cm piece was placed in 100 ml of distilled water at 23 ° C, taken after 5 minutes, carefully dabbed and weighed. The tear strength and elongation at break of the nonwoven fabric were after ISO 9073-3 certainly. The breaking load was greater than 150 N, the elongation at break was 121%.

Example 11:

A 15% strength by weight solution of cationic starch and a 13% strength by weight solution of polyvinyl alcohol, each in distilled water, were prepared. To the polyvinyl alcohol solution was additionally added 1% by weight of glycerin and 1% by weight of sodium alginate. Both solutions were homogenized using an ultrasonic bath (VWR USC 1200D, step 9) for 30 minutes at 60 ° C. The spinning rotor was regulated to a rotation speed of 3500 rpm and heated to 90 ° C. The two solutions were delivered to the spinning rotor with two different syringe pumps (both Harvard syringe pump 11) where the solutions mixed. It was spun for a total of 15 minutes. The cationic starch solution was fed into the spinning rotor at a constant delivery rate of 8 ml / min. The second solution (polyvinyl alcohol, glycerin and sodium alginate) was continuously increased at 0 ml / min for 15 minutes to a flow rate of 4 ml / min. The fibers were deposited after leaving the spinning rotor (diameter of the spinning openings 0.2 mm) at 23 ° C on a suction below the rotor. The extraction was set to 60 m ³ / h at the beginning of the spinning process. This gave a 3.5 mm thick nonwoven ( ISO 9073-2 ) having a basis weight of 260 g / m ² ( ISO 9073-1 ), whose top also differed noticeably from the bottom. The resulting nonwoven was post-treated for 4 hours at 120 ° C in a vacuum oven (5 mbar). The water absorption of the nonwoven was 17 times its dry own weight. For this purpose, a 10 × 10 cm piece was placed in 100 ml of distilled water at 23 ° C, taken after 5 minutes, carefully dabbed and bent. While the underside of the web assumed a gel-like consistency, the fleece structure of the top remained intact. The tear strength and elongation at break of the nonwoven fabric were after ISO 9073-3 certainly. The breaking load was 100 N, the elongation at break was greater than 130%.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been 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.

Cited patent literature

• WO 2008/107126 A1 [0002]
• WO 2009/036958 A2 [0002]
• WO 2012/022422 A1 [0003]
• US 2007/0087061 A1 [0004]
• WO 2009/091549 A1 [0005]
• US 2012/0216709 A1 [0006]

Cited non-patent literature

• ISO 9073-2 [0057]
• EN ISO 9237 [0059]
• ISO 9073-3 [0066]
• Adomačiūtė E, Milašius R, Žemaitaitis A, Bendoraitienė J, Leskovšek M, Demšar A. Fibers & Textiles in Eastern Europe, 2009; 17, 3 (74): 29-33. [0131]
• ISO 9073-2 [0131]
• ISO 9073-1 [0131]
• ISO 9073-3 [0131]
• ISO 9073-2 [0132]
• ISO 9073-1 [0132]
• ISO 9073-3 [0132]

Claims (20)

A fiber product comprising fibers having modified starch, characterized in that the fibers are made by means of rotational spinning. A fiber product according to claim 1, characterized in that the modified starch is selected from the group comprising physically modified starch, chemically modified starch, enzymatically modified starch, naturally modified starch and mixtures thereof. A fiber product according to claim 2, characterized in that the physically modified starch is selected from the group comprising radiation-modified starch, mechanically modified starch, steam-modified starch and mixtures thereof. Fiber product according to claim 2, characterized in that the chemically modified starch is selected from the group comprising acid-modified starch, alkali-modified starch, bleached starch, oxidized starch, esterified starch, etherized starch, crosslinked starch, hydrophilized starch, acetylated starch, phosphorylated starch, grafted Starch and mixtures thereof. Fiber product according to one of the preceding claims, characterized in that the fibers each have a proportion of the modified starch of 50 wt .-% to 99 wt .-%, in particular 65 wt .-% to 95 wt .-%, preferably 65 wt. % to 75% by weight, based on the total weight of a single fiber. Fiber product according to one of the preceding claims, characterized in that the fibers each further comprise a plasticizer, in particular selected from the group comprising sugar alcohols, alcohols, polyalcohols, polyethers, Natriumcelluloseglykolat, polyvinyl acetate, polyvinylpyrrolidine and mixtures thereof. Fiber product according to claim 6, characterized in that the fibers each have a proportion of the plasticizer of 1 wt .-% to 50 wt .-%, in particular 5 wt .-% to 40 wt .-%, preferably 20 wt .-% to 35 wt .-%, based on the total weight of a single fiber. Fiber product according to one of the preceding claims, characterized in that the fibers each further comprise a filler, in particular selected from the group consisting of the group comprising crosslinked and especially low molecular weight polyvinyl alcohol, crosslinked polyvinyl acetate, crosslinked polyvinylpyrrolidone, polyvinyl ureas, dextrans, sodium cellulose, glycolate, croscaramellose, hydroxyalkylcelluloses such as hydroxypropylmethylcellulose, hydroxyalkylcelluloses such as hydroxypropylmethylcellulose, hydroalkylcelluloses such as hydroxyethylcellulose, alkylcelluloses such as methylcellulose, microcellulose, pectin, gellan, alginates, salts thereof, and mixtures thereof. Fiber product according to claim 8, characterized in that the fibers each have a proportion of the filler of 0 wt .-% to 10 wt .-%, in particular 0.1 wt .-% to 5 wt .-%, preferably 1 wt .-% to 5 wt .-%, based on the total weight of a single fiber. Fiber product according to one of the preceding claims, characterized in that the fiber product is mechanically solidified, preferably by means of water jetting and / or pressing. Fiber product according to one of the preceding claims, characterized in that the product has a tensile strength of 0.15 N / mm ² to 3 N / mm ² , in particular 0.5 N / mm ² to 2 N / mm ² , preferably of about 1 N / mm ² , having. Fiber product according to one of the preceding claims, characterized in that the fibers are deposited using a material gradient, in particular with respect to the modified starch. Fiber product according to one of the preceding claims, characterized in that the fiber product comprises fibers or fiber fractions with different modified starch content. Fiber product according to claim 13, characterized in that the modified starch portion over the width or thickness of the fiber product, in particular from one side to another, preferably opposite side of the fiber product, a gradient follows. Fiber product according to one of the preceding claims, characterized in that the fiber product is a sheet, preferably a nonwoven or nonwoven fabric. Fiber product according to one of the preceding claims, characterized in that the fiber product is intended for use as a medical implant. Process for producing a fiber product, in particular according to one of the preceding claims, in which, starting from a fiber raw material which has modified starch, fibers are produced by means of rotational spinning. A method according to claim 17, characterized in that the fiber raw material is placed in a container, wherein the container is rotated and wherein the fiber raw material is discharged by Zentripetalkräfte from the container in the form of fibers. A method according to claim 17 or 18, characterized in that the fibers produced are solidified, in particular by means of water jetting and / or pressing, for example with the aid of a sand punch or a calender. Method according to one of claims 17 to 19, characterized in that the proportion of modified starch in the fiber raw material during the rotation spinning is preferably changed gradually.