DE102011016739A1 - Coating system, useful to produce a medical product, preferably to seal tissue defects of the skin and in the mouth/nose areas, comprises poly(vinyl butyral-co-vinyl-alcohol-co-vinylacetate) and poly(1-vinylpyrrolidone-co-vinylacetate) - Google Patents

Abstract

Coating system comprises component (a) poly (vinyl butyral-co-vinyl alcohol-co-vinyl acetate) with a molecular weight of 10000-120000 g/mole and the component (b) poly (1-vinylpyrrolidone-co-vinyl acetate) with a molecular weight of 3500-70000 g/mole. The weight ratio of components (a) and (b) is 99:1-1:99, preferably 75:25, 70:30 or 65:35 and the coating is applied by dipping and overlapping, in which the layer thickness of the coating is less than 100 mu m, which is based on the number of dipping steps.

Description

The present invention relates to the development of coating materials and their use for the flexible coating of shape-changing bodies, in particular osmosis expanders for tissue expansion and the coating of medical aids made of glass, ceramic, metal, plastics and textiles.

Tissue expanders are among the indispensable aids in plastic surgery, in the field of scar and neoplastic surgery and special applications such. B. the treatment of congenital clinical anophthalmos. There are two main types of tissue expanders. These are balloon expanders and hydrogel-based expander. At present, essentially the conventional balloon expanders (silicone balloons) are still used. These consist of a silicone sheath, which are filled after implantation and initial wound healing by filling with saline solution by means of a cannula via a remote from the skin expanderfernes valve. On the one hand, this involves pain for the patient during filling and the resulting strong stretching in a short time. On the other hand, there is a considerable expenditure of time and personnel due to a necessary repeated filling in a medical facility. In addition, the shapes are limited for these expander and especially for smaller dimensions can not be used. Also for indications such. As in ophthalmology and dentistry, these balloons are not used.

The only supplier of tissue expanders based on hydrogels is osmed gmbh, Ilmenau ( DE 4219207 C2 . EP 0598881 B1 ). The basis of the expander used is a copolymer of N-vinylpyrrolidone and methyl methacrylate. Saponification of these copolymers results in high swelling factor products that swell very much, especially in the first few days after implantation. This rapid stretching and the associated stretching of the skin leads to heavy stress on the surgical suture, which can lead to seam dehiscences. Therefore, a method has been developed to slow the swelling. This could be achieved by wrapping with a perforated silicone sheath. Although swelling starts immediately after insertion, this procedure slows down so much that the suture is less stressed. However, this system reaches its limits when required high swelling, since the silicone shell is only limited elastic and therefore already at the beginning about 3 times the volume of the expander must have. The resulting "folding of the silicone sheath therefore requires a larger incision. Therefore, new methods are being sought which allow for the introduction of small expander with high swelling, while providing a slow swelling and associated slow stretch, thereby avoiding suture discord and pain for the patient. With an expander coating of resorbable polymers (Burg et al., Absorbable Tissue Expander, US 2002/0010514 A1 ), the existing problems could not be solved satisfactorily so far. These expanders use a similar balloon as the silicone expanders described above. This consists of resorbable polymers based on polylactide. While this may affect the swelling via degradation of the biomaterial, the size and rigidity of the shells as well as limitations in the swelling value remain a problem. Furthermore, degradation products of polylactides can exert adverse effects on healing processes and cause hystiocytic reactions.

It is therefore an object of the present invention to provide flexible and stretchable coating materials which conform to the shape of the tissue expander and allow for delayed swelling of the tissue expanders at high swelling levels, thereby making it possible to access expander in small dimensions. The coating material should be biocompatible and form no toxic degradation products during prolonged implantation.

According to the invention, the object is achieved by using a two-component polymer system based on polyvinyl acetate copolymers.

The coating system of the invention is based on a two-component system of poly (vinyl butyral-co-vinyl alcohol-co-vinyl acetate) (PVVV) and poly (1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) in various blends.

Due to the novel coating, it is possible to precisely adjust the swelling behavior of the tissue expander and thereby delay the swelling rate. This delay ensures that before the onset of the swelling process, the wound heals to such an extent that the occurrence of seam dehiscences can be avoided.

The coating of the present invention is preferably used to coat osmotic expanders with swelling factors in the range of 2-40, replacing the bulky silicone sheath of limited extensibility previously used for swelling rate reduction.

The coating system according to the invention can furthermore advantageously be used for sealing wounds and tissue defects in the oral / Nose area and / or skin defects.

Furthermore, other materials such as glass, metal, ceramics, plastics and textiles can be coated with a very small layer thickness.

• • Durch Verkleinerung der Ausgangsexpander sind kleinere Schnitte möglich und damit auch eine geringere Narbenbildung verbunden
• • Durch die verzögerte Quellung kommt es erst zu Dehnungen, wenn das Gewebe im Nahtbereich schon weitestgehend verheilt ist, somit ist keine Belastung der Naht zu erwarten (die derzeitig verwendeten Expander quellen sofort nach dem Einbringen)
• • Quellung beginnt erst nach 7–12 Tagen und dann relativ langsam, somit schonende Expansion mit hohen Dehnungen möglich
• • effektive Gewebedehnung mit gesteuerter Expansion, hoher Dehnung und ohne weitere Behandlung oder Nachoperation der Patienten
• • Verwendung silikonfreier Materialien
• • Vielzahl an Formvariationen mit Beschichtung statt Hülle, kleine und asymmetrische Implantate möglich

The following advantages could be achieved with the coating system according to the invention:

• • Smaller cuts are possible by reducing the size of the output expanders, which also reduces scarring
• • Due to the delayed swelling, expansion only occurs when the tissue in the suture area has healed as far as possible, so no strain on the suture is to be expected (the currently used expanders swell immediately after insertion)
• • Swelling begins only after 7-12 days and then relatively slowly, thus gentle expansion with high strains possible
• • Effective tissue dilation with controlled expansion, high elongation and no further treatment or reoperation of patients
• • Use of silicone-free materials
• • Variety of shape variations with coating instead of shell, small and asymmetrical implants possible

The coating system consists of two components:
Component 1: poly (vinyl butyral-co-vinyl alcohol-co-vinyl acetate), M _w = 10,000-120,000 g / mol, Tg = 72-78 ° C
Component 2: Poly (1-vinylpyrrolidone-co-vinyl acetate), M _w = 3500 to 70,000 g / mol, Tg = 64 ° C

Furthermore, the production of the coating system according to the invention is carried out in organic solvents. Suitable solvents are ethyl acetate, chloroform, but especially methanol and / or acetone, but preferably ethanol.

The weight ratios in the coating system according to the invention are in the range from 99: 1 to 1:99, in particular from 80:20 to 20:80, particularly preferably 75:25, 70:30 and 65:35.

Further, component 1 can be used alone as a coating material.

Furthermore, in the method according to the invention, components 1) and 2) are present separately from one another.

Furthermore, however, in the method according to the invention, a prior mixing of components 1 and 2 can take place.

Furthermore, in the method according to the invention, components 1) and 2) can be dissolved in organic solvents, preferably in ethanol. Furthermore, the components of the two-component system are already present in a usable ratio.

Furthermore, in the coating process according to the invention, symmetrical and asymmetric tissue expanders can be coated.

Furthermore, the tissue expanders are coated by mutual or full immersion,
preferably by mutual overlapping dipping, the overlap being 2-80%, preferably 5-30%.

Furthermore, the dive is carried out 1-20 times, in particular 5 times alternately. Furthermore, in the coating method according to the invention, silicone holder forms for small tissue expanders (G: 0.1-1 g, ⌀: 3-10 mm) with a number of samples of 10 are used.

Furthermore, metal / Teflon holders for large tissue expander (G: 4-40 g, ⌀: 15-40 mm) with a number of samples of 5 are used in the coating method according to the invention.

Furthermore, in the coating method according to the invention, a drying time interval between the individual dips of 10-90 min, preferably 20-30 min.

Furthermore, the coating system of the invention is an effective and flexible coating, which is suitable in combination with a hydrogel-based osmotic expander as a medical device.

Furthermore, the coating system according to the invention, characterized in that the medical device is a product for coating of variable (non-static) moldings (swelling, expansion).

Furthermore, the coating system according to the invention, characterized in that the medical device is suitable for the coating of different materials such as glass, metal, plastics and textiles.

Furthermore, the coating system according to the invention, characterized in that the Coating material as a medical device is suitable for sealing tissue defects in the mouth / nose area.

Furthermore, the coating system according to the invention, characterized in that the coating material is suitable as a medical device for sealing skin wounds.

The invention will be explained below by way of examples, without being limited to these examples.

Example 1: Preparation of the dipping solution (80:20) with prior mixing

800 mg of poly (vinyl butyral-co-vinyl alcohol-co-vinyl acetate) and 200 mg of poly (1-vinylpyrrolidone-co-vinyl acetate) are dissolved with 18 ml of ethanol with stirring overnight.

To remove solid particles, this solution is filtered through a 0.45 μm syringe filter. The dipping solution is transferred to the appropriate immersion vessel with stirrer.

Example 2: Preparation of the dipping solution (70:30) without prior mixing

700 mg of poly (vinyl butyral-co-vinyl alcohol-co-vinyl acetate) and 300 mg of poly (1-vinylpyrrolidone-co-vinyl acetate) are separately dissolved in 9 ml of ethanol with stirring overnight. Both solutions are each filtered through a 0.45 micron syringe filter and intimately mixed with each other just before the actual dip coating.

Example 3: Coating Process

• • Silikonhalterung: für kleine Gewebeexpander (G: 0,1–1 g, ⌀: 3–10 mm) mit einer Probenzahl von 10
• • Halter aus Metall/Teflon: für große Gewebe-Expander (G: 4–40 g, ⌀: 15–40 mm) mit einer Probenanzahl von 5

The expander specimens are clamped in the sample holder:

• • Silicone holder: for small tissue expanders (G: 0.1-1 g, ⌀: 3-10 mm) with a sample number of 10
• • Metal / Teflon holder: for large tissue expander (G: 4-40 g, ⌀: 15-40 mm) with a sample number of 5

The sample holders are screwed into the texture analyzer and prepared for dipping.

The samples are then slowly immersed in the solution at a rate of 10 mm / min (immersion solution is stirred about 200-300 rpm) and remain there for 20 s. Thereafter, the test pieces are removed from the dipping solution at the same speed and dried in air for 20 minutes.

The depth should be 5-30% but preferably about 2-5 mm to more than half of the specimen (depending on the expander type) to ensure an overlapping dive. After drying, the specimens are rotated and stretched with the other side in the sample holder.

Now the diving process starts again under the same conditions.

5 dives alternating (overlapping) have been proven so far. Thereafter, the drying takes place over 24 h.

Example 4: Coating of titanium test specimens

The titanium test specimens (2 × 5 × 10 mm, H × W × L) were coated by immersion in a dipping solution (80:20). The layer thickness per dive corresponds to approx. 10 μm, determined by step measuring method (Dektak 3ST, Veeco / Sloan)). The dipping solution was prepared according to Example 1.

The result was a thin and strong adhesive coating on the surface. Thus it is possible, among other things, to coat titanium implants.

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

• DE 4219207 C2 [0003]
• EP 0598881 B1 [0003]
• US 2002/0010514 A1 [0003]

Claims (10)

Coating system for a substrate coating, characterized in that the coating system on the substrate - from the component 1: poly (vinyl butyral-co-vinyl alcohol-co-vinyl acetate) having a molecular weight in the range M _w = 10,000-120,000 g / mol and the component 2: poly (1-vinylpyrrolidone-co-vinyl acetate) having a molecular weight in the range M _w = 3500-70,000 g / mol, - components 1 and 2 have a weight ratio of 99: 1 to 1:99, in particular 80: 20 to 20:80, more preferably 75:25, 70:30 and 65:35, and - is applied by overlapping dipping, wherein the layer thickness of the coating, depending on the number of immersions <100 microns Coating system according to claim 1, characterized That component 1 and component 2 are present separately from each other before mixing, and - Both components are dissolved in medically applicable / compatible solvents, wherein the solvent is ethanol or 90-99% aqueous ethanol solution Coating system according to at least one of the preceding claims, characterized in that the coating system is suitable for the production of a flexible and extensible coating material. Coating system according to at least one of the preceding claims, characterized in that it is a product for coating different materials such as glass, ceramic, metal and polymer / plastic surfaces. Coating system according to at least one of the preceding claims, characterized in that the coating is suitable for deformable symmetrical and asymmetric bodies (swelling, expansion). Coating system according to at least one of the preceding claims, characterized in that the coating is particularly suitable for symmetrical and asymmetric osmotic expander especially for self-filling tissue expander for tissue expansion. Coating system according to at least one of the preceding claims, characterized in that the swelling time of the tissue expander can be adjusted by varying the weight ratios in the mixture of components 1 and 2. Coating system according to at least one of the preceding claims, characterized in that the coating material is biocompatible. Coating system according to at least one of the preceding claims, characterized in that the coating is carried out with silicone and / or metal / Teflon holders, wherein at the same time 1-100, preferably 5-10 tissue expanders are coated. Coating system according to at least one of the preceding claims, characterized in that the coating system comprising component 1 and component 2 is suitable for producing a medical device, in particular for sealing tissue defects of the skin and in the mouth / nose region.