JP2007236974A - Multi-layer nonwoven tissue containing surface layer which comprises at least one hyaluronate - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a multi-layer nonwoven material which has good mechanical and liquid-absorbing characteristics, is flexible and soft, and is non-adhesive to the skin. <P>SOLUTION: In the multi-layer nonwoven material which comprises a surface layer which touches the skin, and one or more other layers which do not touch the skin, the surface layer which touches the skin, is chosen from a group which consists of a surface layer comprising at least one hyaluronic acid derivative, a surface layer which comprises a mixture of at least one hyaluronic acid derivative and at least one natural polymer, a semi-synthetic polymer, or a synthetic polymer, and a surface layer which comprises natural, synthetic, and semi-synthetic biocompatible porous membranes which can be compatible with cell growth on the surface. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a novel material, namely a multilayer nonwoven structure in which one of the layers comprises a hyaluronic acid derivative.

  Various types of products have been created from research aimed at obtaining biomaterials that consist of hyaluronic acid esters used on their own or in mixtures with other polymers and provide a good skin covering. Tissues such as the gauze and film described in US Pat. Nos. 4,851,521 and 4,965,353 have been proposed. Limitations on the use of such products as skin coatings are due to their stiffness, which can vary depending on how they are manufactured, and are such as body fluids that exude from the wound during tissue repair. , Due to their poor liquid absorption. By utilizing nonwoven tissue manufacturing technology, it is possible to obtain a product that combines flexibility with the ability to absorb liquids strongly. These properties are described in various patents such as US Pat. No. 5,041,104.

Limitations to the use of products made of hyaluronic acid derivatives and / or mixtures thereof obtained using currently known techniques are largely due to the following:
(1) Poor mechanical properties of the material when wet, due to its tendency to form a gel when in contact with aqueous liquids such as physiological body fluids;
(2) hyaluronic acid derivatives or other biocompatible and bioabsorbable polymers, resulting in a high cost end product despite the fact that the polymer is only needed for the layer that is in direct contact with the application site Overuse of expensive materials such as mixtures thereof; and (3) excessively high water vapor transmission values.
These disadvantages are particularly important when exudate production is poor.
U.S. Pat. No. 4,851,521 U.S. Pat. No. 4,965,353 US Pat. No. 5,041,104

  Accordingly, it is an object of the present invention to provide a multilayer nonwoven material consisting of a surface layer that contacts the skin and one or more other layers that do not contact the skin, in which the skin The surface layer in contact with a surface layer comprising at least one hyaluronic acid derivative, a surface comprising at least one hyaluronic acid derivative and a mixture of at least one natural polymer, semi-synthetic polymer, or synthetic polymer And a surface layer consisting of a natural, synthetic or semi-synthetic biocompatible porous membrane compatible with cell growth on the surface. In a preferred embodiment, the layer in contact with the skin comprises a hyaluronic acid derivative, ie a compound containing a hyaluronic acid moiety, in particular a hyaluronic acid ester or a mixture thereof.

  Such products have good mechanical and liquid absorption properties, are soft and soft, are affordable and can vary in their permeability to water vapor.

  Another object of the present invention includes natural, synthetic, or semi-synthetic materials in which one or more other layers that do not contact the skin act as reinforcements and / or liquid absorption systems for the multilayer nonwoven material. Providing a multi-layered nonwoven material consisting of: and thus reducing the amount of biocompatible and bioabsorbable polymer to a minimum and concentrating their action in areas where it is needed.

  A further object of the present invention is a multilayer nonwoven material as described above, wherein the surface layer in contact with the skin and one or more other layers not in contact with the skin are chemically coagulant, adhesive and machine Providing a multilayer nonwoven material that is secured together with at least one selected from the group consisting of mechanical stitching.

  Such multi-layer nonwoven materials are used as non-adhesive hygiene or surgical supplies in, for example, dermatology, dermatology such as skin treatment, dental stomatology, orthopedics, neurosurgery, and ear or nose treatment Can be used.

  Further scope of applicability of the present invention will become apparent from the detailed description provided hereinafter. However, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description, the detailed description and specific examples illustrate the preferred embodiments of the invention. It should be understood that it is suggested but only given as an example.

The following detailed description of the invention is provided to assist those skilled in the art in practicing the invention. However, since the modifications and variations of the embodiments discussed herein can be made by those skilled in the art without departing from the spirit or scope of the discovery of the present invention, the following detailed description unduly limits the present invention. Should not be interpreted as such.
The contents of each document cited in this specification constitute a part of this specification in its entirety.

  The foregoing and other objectives include a basis weight of 20 g / mq to 500 g / mq, a thickness of 0.5 mm to 20 mm, a minimum of 2 to 4 layers, and a water absorption percentage relative to their weight of 60% to 150%. Also achieved by the multilayer nonwoven structure according to the present invention, which has a water vapor permeability of 100-4500 g / mq in 24 hours.

  A multi-layered nonwoven tissue can be described as a material consisting of several layers secured together with a chemical coagulant and / or adhesive, or by mechanical suturing. Each layer consists of fibers having a diameter varying between 8 and 60 micrometers and a length of 5 to 100 mm and is joined together with a chemical coagulant or adhesive, or by mechanical stitching.

  The layer to be in contact with the skin is as described in EP 0216453 and U.S. Pat. Nos. 4,851,521, 4,965,353, and 5,202,431. It comprises hyaluronic acid esters and is used alone or in various percentage mixtures. In addition, this layer can also contain collagen or collagen and glycosaminoglycan coprecipitates, cellulose, chitin, chitosan, pectin, or pectic acid, agar, agarose, xanthene gum, gellan, alginic acid, various alginate , Alginate, polymannan or polyglycan, gel-like polysaccharides such as starch, fibers obtained from natural polymers such as natural rubber, or bridges such as aldehydes or their precursors, dicarboxylic acids or their halides, diamines Collagen cross-linked collagen, cellulose, alginic acid, starch, hyaluronic acid, chitin, chitosan, gellan, xanthene, pectin, pectic acid, polyglycan, polymannan, agar, agarose, natural gum, glycosa Fibers obtained from semi-synthetic derivatives of natural polymers such as noglycan derivatives, or fibers obtained from synthetic polymers such as polylactic acid, polyglycolic acid or copolymers thereof or polydioxanes, polyphosphazenes, polysulfones, and polyurethanes And a mixture of hyaluronic acid ester fibers.

  As used herein, the term “derivative” refers to a compound containing the indicated moiety. For example, the term “cellulose derivative” refers to a compound containing a cellulose moiety.

  A top layer having the function of reinforcing the product and / or absorbing liquid and adjusting the permeability to water vapor can be in the form of a non-woven or loom-woven structure. They can be composed of natural fibers such as cotton, regenerated fibers such as viscose rayon, or synthetic polymer fibers such as polyester, polyamide, polyalkylene, or mixtures thereof. Furthermore, the layer can consist of a flexible foam such as polyurethane or an elastomeric synthetic membrane such as elastic silicone or elastic polyurethane.

  The various layers are fixed together than is typical for nonwoven tissue techniques. These include, for example, compressing fiber layers as described in Nonwoven Technologies for Sanitary Absorbent Products, pages 185-190, or various Mechanical sewing methods or chemical methods using coagulants or adhesives suitable for joining the types of layers are included. An example adhesive is Acronal DS 2331 X, which is an acrylate binder.

  The present invention therefore relates to a new product, multilayer nonwoven tissue, for use in the medical / pharmaceutical field for coating the skin and also in external medicine. The surface in contact with the skin comprises at least one hyaluronic acid ester used by itself or in a mixture with other natural or synthetic polymers. Other layers comprising synthetic or semi-synthetic materials act as material reinforcements and / or liquid absorption systems.

The surface layer in contact with the skin can also consist of a natural, synthetic, or semi-synthetic biocompatible porous membrane that is compatible with cell growth on the surface. Examples of such natural and semi-synthetic biocompatible porous membranes are described in European Patent Application No. 0462426. Natural materials useful for such membranes include collagen or coprecipitates of collagen and glycosaminoglycans, cellulose, in the presence of a suitable precipitating or gelling agent such as a metal salt, polycation, or polyanion. , Chitin, chitosan, pectin, pectic acid, agar, agarose,
Gelled polysaccharides such as xanthene gum, gellan, alginic acid, alginate, polymannan, polyglycan, starch, or natural rubber are included alone or in a mixture with each other or with a synthetic or semi-synthetic polymer. The Examples of synthetic biocompatible porous membranes useful for the multilayer nonwoven tissue of the present invention include polylactic acid, polyglycolic acid, copolymers or derivatives thereof, polydioxane, polyphosphazene, polysulfone, polyurethane, dialdehyde or Collagen crosslinked with crosslinking agents such as their precursors, dicarboxylic acids or their halides, diamines, or cellulose, alginic acid, starch, chitin, chitosan, gellan, xanthene gum, pectin, pectic acid, polyglycan, Included are semi-synthetic derivatives of natural polymers such as polymannan, agar, agarose, natural rubber, or glycosaminoglycan derivatives. Such synthetic membranes also include fluoropolymers such as silicon, silane, or siloxane rubber, polyfluoroethylene, polyfluoropropylene, polyfluoroether, polystyrene, polyvinyl chloride, polyacrylate or derivatives thereof, polyhydroxyacrylate, It also comprises non-biodegradable synthetic polymers such as polyhydroxymethacrylate, carboxyvinyl polymers and their derivatives, maleic anhydride polymers and their derivatives, polyvinyl chloride, polyvinyl alcohol and its derivatives, polyethylene, and polypropylene. obtain.

  The nonwoven tissue of the present invention can also be impregnated with a solution of antibiotics, preservatives, antimicotics, polypeptides, proteins, or other types of pharmaceutically active compounds.

  The properties of the novel materials of the present invention include otologic and oto neurological microsurgery, post-traumatic and endoscopic functional nasal sinus microsurgery, plastic and rehealth surgery, and their anti-adhesion properties They make them particularly valuable for use in the field of external sciences, such as other surgical instructions that require the use of materials having the properties claimed in the present invention.

  For purposes of illustration only, some examples of multilayer nonwoven structures according to the present invention are reported below.

Example 1
The following procedure consisted of a layer of hyaluronic acid benzyl ester, a layer of HYAFF 11 and a non-woven viscose layer (Jettex 2005 from ORSA) with a basis weight of 80 g / mq, a thickness of 2 mm, and water A multilayer nonwoven structure with an absorption percentage of 560% by weight was obtained.
The layer in contact with the skin consists of fibers of HYAFF 11 manufactured by a wet spinning technique and made into a 30 g / mq sheet. The fibers were made into sheets as described in WO 93/11803.
The layers are joined together by stitching to a second layer of nonwoven viscose structure having a basis weight of 30 g / mq.
Thus, the final nonwoven product consists of two fully bonded layers with a total basis weight of 80 g / mq, a thickness of 2 mm and a water absorption percentage of 560% by weight.

Example 2
According to the following procedure, it consists of hyaluronic acid ethyl ester, HYAFF 7 layer, and non-woven polyester layer (Best Bond 20 PS manufactured by FNT), with a basis weight of 50 g / mq, thickness of 1 mm, A multilayer nonwoven structure having a water absorption of 400% by weight is obtained.
The layer in contact with the skin is made by wet spinning technology into a 30 g / mq sheet of HYAFF 7 fibers, stitched to a second layer of non-woven polyester with a basis weight of 20 g / mq, Connect this together.
Thus, the final nonwoven product consists of two fully bonded layers with a total basis weight of 50 g / mq, a thickness of 1 mm and a water absorption percentage of 400% by weight.

Example 3
The following procedure consisted of a layer of hyaluronic acid benzyl ester, a layer of HYAFF 11, and a mixed layer of 1: 1 ratio of calcium alginate, and a non-woven fabric of polypropylene (NEUBERGER non-woven substrate, 50 g / mq), A multilayer nonwoven structure having a basis weight of 70 g / mq, a thickness of 1.5 mm and a water absorption percentage of 450% by weight was obtained.
By mixing fibers of HYAFF 11 and calcium alginate 40 mm in length obtained by a conventional wet spinning technique into a 20 g / mq sheet and stitching it to a non-woven tissue having a basis weight of 50 g / mq. And stitched together.
The resulting material consists of a two layer nonwoven structure with a total basis weight of 70 g / mq, a thickness of 1.5 mm, and a water absorption percentage of 450% by weight.

Example 4
The following procedure consisted of a layer of HYAFF 11p75, a 75% partial benzyl ester of hyaluronic acid, and a polyurethane foam layer such as LYOBEND (made by DELCON), with a basis weight of 100 g / mq and a thickness of 5 mm. A multilayer nonwoven structure having a water absorption percentage of 950% by weight was obtained.
The layer in contact with the skin consists of fibers of HYAFF 11p75, produced by wet spinning techniques into 45 g / mq sheets and stitched together by stitching to a second layer of polyurethane foam.
The resulting nonwoven product consists of two layers joined together, with a total basis weight of 100 g / mq, a thickness of 4 mm, and a water absorption percentage of 950% by weight.

Example 5
The following procedure consisted of a layer of hyaluronic acid benzyl ester HYAFF 11 and a polyurethane foam layer such as Rio Bend (Delcon) with a basis weight of 100 g / mq, a thickness of 6 mm and a water absorption percentage of 860. A multilayer non-woven structure having a weight percent was obtained.
The layer in contact with the skin consists of HYAFF 11 fibers made by wet spinning technology and made into a 45 g / mq sheet, which are stitched together by stitching to a second layer of polyurethane foam.
The resulting nonwoven product consists of two fully bonded layers with a total basis weight of 100 g / mq, a thickness of 6 mm and a water absorption percentage of 860% by weight.

Example 6
According to the following procedure, the layer in contact with the skin consists of a mixture of HYAFF 11p75 which is a partial benzyl ester of hyaluronic acid and ALAFF 11 which is a benzyl ester of alginic acid, and the second layer has a density of 55/69 Kg / cc. It is made of a polyurethane foam cushion such as DS 50 foam (FOAM) (made by ORSA) (UNI regulations 6349), and the third layer is made of a polyurethane membrane having a water vapor permeability of 426 g / mq in 24 hours. A multilayer nonwoven structure consisting of three layers, having a basis weight of 200 g / mq and a thickness of 3 mm was obtained. The preparation of all and partial esters of ALAFF 11 and other alginic acids is described in EP 0251905 and US Pat. No. 5,264,422.
The 40 mm long HYAFF 11 and ALAFF 11 fibers obtained by the wet spinning process are stitched to the surface of the polyurethane foam cushion while the other surface is coated with DURO-TAK 380-1054 adhesive. Attached to the polyurethane film. The final material consisted of three layers with a final basis weight of 200 g / mq, a thickness of 8 mm, a water absorption percentage of 1100% by weight, and a water vapor permeability value of 450 g / mq over 24 hours.

Example 7
According to the following procedure, it consists of a layer of HYAFF 11 which is benzyl hyaluronic acid ester, and a non-woven viscose layer (JETEX 2005 manufactured by ORSA), has a basis weight of 80 g / mq and a thickness of 2 mm. A multi-layered nonwoven structure joined to a HYAFF 11 membrane with 0.5 mm holes produced as described in patent application 0462426 was obtained.
After spraying the HYAFF 11 / DMSO solution at a concentration of 60 mg / ml on the surface of HYAFF 11, which is a non-woven tissue obtained as described in Example 1, it has a porosity of 0.5 mm. Affix the membrane. The membrane and nonwoven tissue are then pressed together, immersed in an ethanol bath, washed and dried.
The nonwoven structure thus obtained has a basis weight of 80 g / mq, a thickness of 2 mm, and is composed of three layers, one of which is a porous membrane having 0.5 mm pores. Form.
Obviously, the invention thus described can be modified in various ways. Such modifications are not to be regarded as a departure from the spirit and purpose of the invention, and all modifications that will be apparent to those skilled in the art are included within the scope of the following claims.

Claims (29)

A non-adhesive multilayer nonwoven material comprising a surface layer in contact with the skin and one or more other layers not in contact with the skin,
The surface layer in contact with the skin is non-adherent to the skin and comprises at least one hyaluronic acid derivative;
A surface layer comprising at least one said hyaluronic acid derivative and a mixture of at least one natural polymer, semi-synthetic polymer, or synthetic polymer, and natural, synthetic, or semi-compatible with cell growth on the surface Selected from the group consisting of a surface layer comprising a synthetic biocompatible porous membrane;
If the surface layer in contact with the skin comprises a natural synthetic or semi-synthetic biocompatible porous membrane, at least one of the one or more layers not in contact with the skin is liquid absorbent Is a multilayer nonwoven material.   The multilayer nonwoven material of claim 1, wherein the at least one hyaluronic acid derivative is a hyaluronic acid ester.   At least one of the natural polymers is collagen, collagen-glycosaminoglycan coprecipitate, cellulose, chitin, chitosan, pectin, pectic acid, agar, agarose, xanthan gum, gellan, alginic acid, alginate, polymannan, polyglycan, starch And at least one semisynthetic polymer is selected from the group consisting of alginic acid ester, crosslinked collagen, cellulose derivative, alginic acid derivative, starch derivative, hyaluronic acid derivative, chitin derivative, chitosan derivative, gellan derivative, xanthene Selected from the group consisting of derivatives, pectin derivatives, pectic acid derivatives, polyglycan derivatives, polymannan derivatives, agar derivatives, agarose derivatives, natural rubber derivatives, and glycosaminoglycan derivatives; At least one said synthetic polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polylactic acid and polyglycolic acid copolymer, polylactic acid derivative and polyglycolic acid derivative copolymer, polydioxane, polyphosphazene, polysulfone, and polyurethane The multilayer nonwoven material of claim 1.   The one or more other layers that do not contact the skin comprise natural, synthetic, or semi-synthetic materials that act as reinforcing and / or liquid absorption systems for the multilayer nonwoven material. A multilayer nonwoven material as described in 1.   The natural material is cotton, and the synthetic material is selected from the group consisting of viscose rayon, polyester, polyamide, polyalkylene, or a mixture of the above materials, polyurethane, elastic silicone, and elastic polyurethane, and the semi-synthetic material is at least The multilayer nonwoven material of claim 4, which is a hyaluronic acid ester.   The multilayer nonwoven material according to claim 1, wherein the surface layer in contact with the skin comprises at least one hyaluronic acid ester.   The multilayer nonwoven material of claim 6, wherein the at least one hyaluronic acid ester is selected from the group consisting of hyaluronic acid benzyl ester and hyaluronic acid ethyl ester.   The multilayer nonwoven material of claim 7, wherein the benzyl ester of hyaluronic acid is a 75% partially benzyl ester of hyaluronic acid.   The multilayer nonwoven material of claim 1, wherein the surface layer in contact with the skin comprises a mixture of hyaluronic acid benzyl ester and alginic acid benzyl ester.   The multilayer nonwoven material of claim 1, wherein the surface layer in contact with the skin comprises a mixture of hyaluronic acid benzyl ester and calcium alginate.   The multilayer nonwoven material of claim 1, wherein the surface layer in contact with the skin comprises a natural, synthetic, or semi-synthetic biocompatible porous membrane that is compatible with cell growth on the surface.   The natural, synthetic or semi-synthetic biocompatible porous membrane has a regular series of pores having a thickness of 10-500μ and a predetermined uniform size diameter of 10-1000μ, each The multilayer nonwoven material according to claim 11, wherein the holes are separated from the adjacent holes by a distance of 50 to 1000 μm.   The multilayer nonwoven material of claim 11, wherein the semi-synthetic biocompatible porous membrane comprises at least one hyaluronic acid ester.   The multilayer nonwoven material of claim 13, wherein the at least one hyaluronic acid ester is hyaluronic acid benzyl ester.   The natural biocompatible porous membrane is collagen, coprecipitate of collagen and glycosaminoglycan, cellulose, chitin, chitosan, pectin, pectic acid, agar, agarose, xanthan gum, gellan, alginic acid, alginate, polymannan, A substance selected from the group consisting of polyglycans, starches, natural rubber, mixtures of said substances, mixtures of any of said substances with synthetic polymers, and mixtures of any of said substances with semi-synthetic polymers. The multilayer nonwoven material according to 11.   Synthetic biocompatible porous membrane is semi-synthetic of polylactic acid, polyglycolic acid, polylactic acid and polyglycolic acid copolymer, polylactic acid derivative and polyglycolic acid derivative copolymer, polydioxanone, polyphosphazene, polysulfone, polyurethane, natural polymer Derivatives, cellulose derivatives, alginic acid, starch, chitin, chitosan, gellan, xanthan gum, pectin, pectic acid, polyglucan, polymannan, agar, agarose, natural rubber, glycosaminoglycan, silicone, silane, siloxane rubber, fluoropolymer , Polystyrene, vinyl polychloride, polyacrylate, polyacrylate derivatives, polyhydroxyacrylate, polyhydroxymethacrylate, carboxyvinyl polymer, carboxyvinyl polymer The multilayer nonwoven fabric of claim 11, comprising a material selected from the group consisting of a derivative, a maleic anhydride polymer, a maleic anhydride polymer derivative, polyvinyl chloride, polyvinyl alcohol, a polyvinyl alcohol derivative, polyethylene, and polypropylene. material.   17. The semi-synthetic derivative of a natural polymer is collagen crosslinked with a crosslinking agent selected from the group consisting of dialdehydes, dialdehyde precursors, dicarboxylic acids, dicarboxylic acid halides, and diamines. Multi-layer nonwoven material.   The multilayer nonwoven material of claim 16, wherein the fluoropolymer is a material selected from the group consisting of polyfluoroethylene, polyfluoropropylene, and polyfluoroether.   The multilayer nonwoven material of claim 1, wherein the one or more other layers that do not contact the skin comprise viscose.   The multilayer nonwoven material of claim 1, wherein the one or more other layers that do not contact the skin comprise nonwoven polypropylene.   The multilayer nonwoven material of claim 1, wherein the one or more other layers that do not contact the skin comprise polyurethane foam.   Basic weight is 40g / mq to 500g / mq, thickness is 0.5mm to 20mm, fiber diameter is 8μm to 60μm, length is 5mm to 100mm, 2 to 4 layers, water absorption percentage is 60% to 500%, The multilayer nonwoven material according to claim 1, wherein the water vapor permeability is a value of 100 to 4500 g / mq in 24 hours.   The surface layer that contacts the skin and one or more other layers that do not contact the skin are secured together with at least one selected from the group consisting of chemical coagulants, adhesives, and mechanical sutures The multilayer nonwoven material of claim 1.   The multilayer nonwoven material of claim 1, comprising two or more layers stitched together.   The multi-layer nonwoven material of claim 1, wherein the multi-layer nonwoven material comprises two layers that are stitched together and that does not contact the skin, comprising polyurethane foam.   The multilayer nonwoven material of claim 1, wherein the multilayer nonwoven material comprises three layers, wherein the layer in contact with the skin is a biocompatible porous membrane comprising all benzyl esters of hyaluronic acid.   The multilayer nonwoven material of claim 1 comprising a pharmaceutically active compound.   28. The multilayer nonwoven material of claim 27, wherein the pharmaceutically active compound is selected from the group consisting of antibiotics, preservatives, antimitotics, polypeptides, proteins.   Use of the multilayer nonwoven material according to any one of claims 1 to 28 as an anti-adhesive material.