CA2043450C - Gels in the form of highly hydrated self-supporting film, the process for their preparation, and their use in therapy of cutaneous lesions and/or pathologies - Google Patents
Gels in the form of highly hydrated self-supporting film, the process for their preparation, and their use in therapy of cutaneous lesions and/or pathologies Download PDFInfo
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- CA2043450C CA2043450C CA002043450A CA2043450A CA2043450C CA 2043450 C CA2043450 C CA 2043450C CA 002043450 A CA002043450 A CA 002043450A CA 2043450 A CA2043450 A CA 2043450A CA 2043450 C CA2043450 C CA 2043450C
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- gel
- supporting film
- alginate
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- alkaline
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/225—Mixtures of macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/04—Alginic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/13—Burn treatment
Abstract
This invention provides new gels in the form of highly hydrated self-supporting film, comprising one or more alkaline alginates, an alkaline earth alginate, a polyalcohol and a natural, synthetic or semisynthetic polymer of hydrophilic nature, and their preparation process. These polysaccharide-matrix gels in highly hydrated self-supporting film form are suitable for use as covering and protection materials for cutaneous lesions and/or pathologies in that they are obtainable in self-supporting form in the desired thickness, are transparent, flexible, have good mechanical characteristics, are adaptable to the lesion surface without strongly adhering to it, and are permeable to gas but are impermeable to liquids and bacteria; one or more pharmacologically active substances can also be incorporated in the gel.
Description
z~4~~~~
GELS IN THE FORM OF HIGHLY HYDRATED SELF-SUPPORTING FILM, THE
PROCESS FOR THEIR PREPARATION, AND THEIR USE IN THE THERAPY OF
CUTANEOUS LESIONS AND/OR PATHOLOGIES
Field of the invention This invention relates to new gels in the form of highly hydrated self-supporting film, the process for their preparation and their use in the therapy of cutaneous lesions and/or pathologies.
Prior art Hydrogels consisting of synthetic or semisynthetic polymers or lp synthetic polymers with small additions of natural polymers and having the characteristic of being only slightly or not reabsorbable are already known for the treatment of cutaneous lesions.
Xerogels, ie anhydrous gels consisting of fibres of calcium alginate presented in the form of bioreabsorbable unwoven tissue.
are also known.
Protective film of various types used for treating cutaneous lesions are also known.
For example, DE patent 30 17 221 describes an ointment containing a soluble alkaline met~l alginate salt which when applied to the lesion and treated in situ with a soluble calcium salt forms a protective film of Ca alginate; to obtain this film the ointment must be reconstituted at the moment of use.
WO patent 80/02300 describes the process for preparing an unwoven tissue based on calcium alginate fibres.
US patent 4,393,048 describes a gel containing an alkaline metal alginate and glycerol for wound medication which on drying forms a protective adhering film, and US patent 4,391,799 describes the same gel in association with silver salts for treating white phosphorus burns.
European Patent 89,152 describes wound medications in the form of hydrogel membranes composed of hydrophilic biopolymers derived from keratin, glycosaminoglycan or collagen.
US patent 4,664,105 describes a wound medication composed of granulated cellulose material or a polysaccharide.
Gels in the form of highly hydrated self-supporting alginate-based film have never been described.
An object of the present invention is to provide a wound medication in the form of a thin self-supporting film which maintains a high degree of hydration for a prolonged time, this being of known and considerable importance for the repair to take place in a short time and within the dictates of the process physiology, to result in cicatrices with optimum characteristics both from the physiological and from the aesthetic aspect.
A further object of the present invention is to provide a wound medication in the form of a bioreabsorbable film, this characteristic allowing the medication to be replaced at a much lesser rate, thus avoiding further irritation to the lesion and facilitating the reparative process.
A further object of the invention is to provide a wound medication in the form of a film with good mechanical characteristics which is soft, pliable, easily handled and properly adaptable to the lesion, but which is only slightly adhesive and can therefore be easily removed without damaging the newly formed tissues, and further which is non-toxic, sterilizable in an autoclave and by gamma rays, compatible with a large number of drugs, therefore allowing their incorporation, does not need to be reconstituted at the moment of use, can absorb exudates, is permeable to gases but not to liquids or bacteria, and which is transparent to enable the development of the reparative process to be followed.
A further object of the invention is to provide a medication which is economically valid in that it reduces the number of medications lp required.
Summary of the invention These and further objects are attained by the composition according to the present invention, which relates to new gels characterised by being in the form of highly hydrated self-suPPorting film comprising one or more alkaline alginates, an alkaline earth alginate, a polyalcohol and a natural, synthetic or semisynthetic polymer of hydrophilic character. In one embodiment of the invention a medicament is dispersed within the gel. These gels in highly hydrated self--supporting film form are prepared by & new process which together with the use of the new film in the therapy of human lesions and/or pathologies also form part of the invention.
Detailed description The gel in highly hydxated self-supporting film form according to the,present invention contains a quantity of between lx and '7.5x, and preferably 3:5x, (all percentages being by weight) of one or more alkaline alginates, preferably sodium alginate; a quantity of between 0.1% and 5%, and preferably 1%, of an alkaline earth alginate, preferably calcium alginate; a quantity of between 0.1%
and 10%, and preferably 5%, of a polyalcohol, preferably glycerol;
and a quantity of between 0.05% and 10x, and preferably 0.5x, of a natural, synthetic or semisynthetic polymer of hydrophilic character, preferably sodium hyaluronate, plus optionally between about 0.01% and 10% of one or more medicaments, the remainder being water. Other alkaline alginates which can be advantageously used are for example potassium and ammonium alginates.
The described film is obtained with the required characteristics according to the invention by starting from an initial fluid gel containing a quantity of between 3.5% and ~.5%. and preferably 3.5x. of one or more alkaline alginates, preferably sodium alginate, a quantity of between 0.5% and 7.5%, and preferably 5%, of a polyalcohol, preferably glycerol, a quantity of between 0.1%
and 10%, and preferably 0.2x, of a natural, synthetic or semisynthetic polymer of hydrophilic character, preferably sodium hyaluronate, plus optionally a medicament.
The initial fluid gel is extruded by pumping through a slit of adjustable width and thickness, and coagulated by passage through between 2 and 4 successive baths, preferably 2, at controlled temperature, the baths containing one or more soluble calcium salts.
The concentration of Ca2+ ions in the various coagulation baths is between 0.1 and 10x and preferably lx in the first coagulation bath, and 2% in the subsequent baths.
The coagulation bath temperature is between 15°C and 40°C and ~0434~0 preferably 20'C for the first, and 30'C for the subsequent baths.
After passage through the last coagulation bath a highly hydrated gel is obtained in the form of a self-supporting thin film having a thickness variable between 0.1 and 5 mm, preferably 0.4 mm, with 5 a pH of between 5.5 and '7.5, preferably between 6.5 and '7.2. The final film characteristics, such as its mechanical and hydration characteristics, can be varied according to requirements by varying the initial gel composition and the coagulation bath conditions.
In a preferred embodiment of the process according to the invention, the alginate film is prepared by extrusion and coagulation using the device shown in Figure 1.
The initial fluid gel is placed in a container vessel 1 From which it is drawn by a pump 2 operating at a suitable r.p.m., then passed through a filter 3 and fed to the filming extruder 4 comprising a slit of suitable variable size immersed in the first coagulation bath.
Coagulation occurs immediately on leaving the filming extruder, the recovered film being passed below a guide drum 5 immersed in the first coagulation bath. The film then leaves the bath, passes through a dragging roller 6 driven by a motor 7, enters a second coagulation bath through which it is guided by a second drum $, leaves the bath guided by a third drum g and is wound onto a winding reel 12 by a calender 10 driven by a motor 11.
The size-setting of the extruder, the pump r.p.m., the dragging roller speed and the winding roller speed can be varied to define the final characteristics of the film.
2(~434~0 For example a film according to the present invention with a thickness of 300 p is obtained by using the device of Figure 1 under the following operating conditions:
pump r.p.m. : 15 r.p.m. equivalent to a throughput of 18 cc/min size setting of filming extruder: 200 a dragging roller r.p.m.: 2.15 r.p.m.
temperature 1st bath (CaCl2 1~ w/v): 20'C
temperature 2nd bath (CaCl2 2~ w/v): 2'7'C
extruded film length produced per minute: 0.4 m.
Any active principle compatible with the gel composition, such as substances of antiseptic, antibiotic, anti-inflammatory, antihistaminic or other activity, can be incorporated into the gel either alone or in association. The concentration of the active principle incorporated into the gel depends on its pharmacological characteristics, and would represent a quantity such as to make it effective for the purpose of the specific application. The medicament quantity in the compositions of the invention.can vary from about O.Olx to 10~ of the weight of the final product.
The film obtained in this manner can be easily stored, handled and used advantageously as covering or medication material for cutaneous lesions and/or pathologies such as the treatment of wounds of surgical or traumatic origin, burns or lesions of pathological origin such as stasis ulcers, bedsores etc.
Some non-limiting examples of the preparation of self-supporting film according to the invention are described below.
24.5 g of sodium alginate are dispersed at ambient temperature in 250 ml of water under continuous stirring. A viscous gel forms, to which are added 1.4 g of sodium hyaluronate Hyalastine fraction (European patent EP 01385'j2 granted on 25th July 1990), 35 g of glycerol and ~ g of NaCl dissolved in 250 ml of water under stirring, the final solution volume then being adjusted to '700 ml.
Slow stirring, to avoid incorporating air, is then continued for about 20 hours, after which the viscous solution is filtered through a 20 a mesh filter and degassed under vacuum.
The solution is extruded by pumping through a slit of width 12 cm ~d of set thickness, and is coagulated by passing through two successive baths containing calcium chloride, the first at 20'C
with a concentration of lx and the next at 30~C with a concentration of 2x. The film obtained, having a thickness of about 0.250 mm, is wound on a suitable spool, washed by immersion in a water bath for 1 hour and finally stored in an aqueous solution containing 5x glycerol, 0.2x methylparaben, 0.02x propylparaben and 0.2x sodium dehydroacetate.
Following the procedure described in Example 1, 1.4 g of sodium hyaluronate Hyalectine fraction (European patent EP 01385'72 granted on 25th July 1990) are added in place of the Hyalastine fraction, to obtain a film having analogous characteristics to those of the film obtained in Example 1.
50 ml of an aqueous solution containing 0.4 g of hyaluronic acid ethyl ester of ~5x esterification (HYAFF ~ p~5 European patent application EPA 216453 of '7.x.86) are added to 150 ml of an ~o~~~~o aqueous solution containing 7 g of sodium alginate, 10 g of glycerol and 2 g of NaCl. After filtration and degassing, the final solution is extruded and coagulated by the procedure described in Example 1 to obtain 150 g of film with a thickness of 0.250 mm. The film is stored in the solution of glycerol and preservatives described in Example 1.
50 ml of an aqueous solution containing 5 g of polyethyleneglycol 1500 are added to 150 ml of an aqueous solution containing '7 g of ZO sodium alginate, 10 g of glycerol and 2 g of NaCl. After filtration and degassing, the final solution is extruded and coagulated by the procedure described in Example 1 to obtain 150 g of film with a thickness of 0.250 mm. The film is stored in the solution of glycerol and preservatives described in Example 1.
50 ml of an aqueous solution containing 2.5 g of p-(aminomethyl) benzenesulphonamide acetate are added to 150 ml of an aqueous solution containing ~ g of sodium alginate, 10 g of glycerol and 2 g of NaCl. After filtration and degassing, the final solution is extruded and coagulated by the procedure described in Example 1 to obtain 150 g of film with a thickness of 0.250 mm. The film is stored in the solution of glycerol and preservatives described in Example 1.
50 ml of an aqueous solution containing 0.1 g of the neomycin salt of hyaluronic acid partly esterified with ethanol ('75x of the carboxyl groups esterified with ethanol, 25x of the carboxyl 20434~~
GELS IN THE FORM OF HIGHLY HYDRATED SELF-SUPPORTING FILM, THE
PROCESS FOR THEIR PREPARATION, AND THEIR USE IN THE THERAPY OF
CUTANEOUS LESIONS AND/OR PATHOLOGIES
Field of the invention This invention relates to new gels in the form of highly hydrated self-supporting film, the process for their preparation and their use in the therapy of cutaneous lesions and/or pathologies.
Prior art Hydrogels consisting of synthetic or semisynthetic polymers or lp synthetic polymers with small additions of natural polymers and having the characteristic of being only slightly or not reabsorbable are already known for the treatment of cutaneous lesions.
Xerogels, ie anhydrous gels consisting of fibres of calcium alginate presented in the form of bioreabsorbable unwoven tissue.
are also known.
Protective film of various types used for treating cutaneous lesions are also known.
For example, DE patent 30 17 221 describes an ointment containing a soluble alkaline met~l alginate salt which when applied to the lesion and treated in situ with a soluble calcium salt forms a protective film of Ca alginate; to obtain this film the ointment must be reconstituted at the moment of use.
WO patent 80/02300 describes the process for preparing an unwoven tissue based on calcium alginate fibres.
US patent 4,393,048 describes a gel containing an alkaline metal alginate and glycerol for wound medication which on drying forms a protective adhering film, and US patent 4,391,799 describes the same gel in association with silver salts for treating white phosphorus burns.
European Patent 89,152 describes wound medications in the form of hydrogel membranes composed of hydrophilic biopolymers derived from keratin, glycosaminoglycan or collagen.
US patent 4,664,105 describes a wound medication composed of granulated cellulose material or a polysaccharide.
Gels in the form of highly hydrated self-supporting alginate-based film have never been described.
An object of the present invention is to provide a wound medication in the form of a thin self-supporting film which maintains a high degree of hydration for a prolonged time, this being of known and considerable importance for the repair to take place in a short time and within the dictates of the process physiology, to result in cicatrices with optimum characteristics both from the physiological and from the aesthetic aspect.
A further object of the present invention is to provide a wound medication in the form of a bioreabsorbable film, this characteristic allowing the medication to be replaced at a much lesser rate, thus avoiding further irritation to the lesion and facilitating the reparative process.
A further object of the invention is to provide a wound medication in the form of a film with good mechanical characteristics which is soft, pliable, easily handled and properly adaptable to the lesion, but which is only slightly adhesive and can therefore be easily removed without damaging the newly formed tissues, and further which is non-toxic, sterilizable in an autoclave and by gamma rays, compatible with a large number of drugs, therefore allowing their incorporation, does not need to be reconstituted at the moment of use, can absorb exudates, is permeable to gases but not to liquids or bacteria, and which is transparent to enable the development of the reparative process to be followed.
A further object of the invention is to provide a medication which is economically valid in that it reduces the number of medications lp required.
Summary of the invention These and further objects are attained by the composition according to the present invention, which relates to new gels characterised by being in the form of highly hydrated self-suPPorting film comprising one or more alkaline alginates, an alkaline earth alginate, a polyalcohol and a natural, synthetic or semisynthetic polymer of hydrophilic character. In one embodiment of the invention a medicament is dispersed within the gel. These gels in highly hydrated self--supporting film form are prepared by & new process which together with the use of the new film in the therapy of human lesions and/or pathologies also form part of the invention.
Detailed description The gel in highly hydxated self-supporting film form according to the,present invention contains a quantity of between lx and '7.5x, and preferably 3:5x, (all percentages being by weight) of one or more alkaline alginates, preferably sodium alginate; a quantity of between 0.1% and 5%, and preferably 1%, of an alkaline earth alginate, preferably calcium alginate; a quantity of between 0.1%
and 10%, and preferably 5%, of a polyalcohol, preferably glycerol;
and a quantity of between 0.05% and 10x, and preferably 0.5x, of a natural, synthetic or semisynthetic polymer of hydrophilic character, preferably sodium hyaluronate, plus optionally between about 0.01% and 10% of one or more medicaments, the remainder being water. Other alkaline alginates which can be advantageously used are for example potassium and ammonium alginates.
The described film is obtained with the required characteristics according to the invention by starting from an initial fluid gel containing a quantity of between 3.5% and ~.5%. and preferably 3.5x. of one or more alkaline alginates, preferably sodium alginate, a quantity of between 0.5% and 7.5%, and preferably 5%, of a polyalcohol, preferably glycerol, a quantity of between 0.1%
and 10%, and preferably 0.2x, of a natural, synthetic or semisynthetic polymer of hydrophilic character, preferably sodium hyaluronate, plus optionally a medicament.
The initial fluid gel is extruded by pumping through a slit of adjustable width and thickness, and coagulated by passage through between 2 and 4 successive baths, preferably 2, at controlled temperature, the baths containing one or more soluble calcium salts.
The concentration of Ca2+ ions in the various coagulation baths is between 0.1 and 10x and preferably lx in the first coagulation bath, and 2% in the subsequent baths.
The coagulation bath temperature is between 15°C and 40°C and ~0434~0 preferably 20'C for the first, and 30'C for the subsequent baths.
After passage through the last coagulation bath a highly hydrated gel is obtained in the form of a self-supporting thin film having a thickness variable between 0.1 and 5 mm, preferably 0.4 mm, with 5 a pH of between 5.5 and '7.5, preferably between 6.5 and '7.2. The final film characteristics, such as its mechanical and hydration characteristics, can be varied according to requirements by varying the initial gel composition and the coagulation bath conditions.
In a preferred embodiment of the process according to the invention, the alginate film is prepared by extrusion and coagulation using the device shown in Figure 1.
The initial fluid gel is placed in a container vessel 1 From which it is drawn by a pump 2 operating at a suitable r.p.m., then passed through a filter 3 and fed to the filming extruder 4 comprising a slit of suitable variable size immersed in the first coagulation bath.
Coagulation occurs immediately on leaving the filming extruder, the recovered film being passed below a guide drum 5 immersed in the first coagulation bath. The film then leaves the bath, passes through a dragging roller 6 driven by a motor 7, enters a second coagulation bath through which it is guided by a second drum $, leaves the bath guided by a third drum g and is wound onto a winding reel 12 by a calender 10 driven by a motor 11.
The size-setting of the extruder, the pump r.p.m., the dragging roller speed and the winding roller speed can be varied to define the final characteristics of the film.
2(~434~0 For example a film according to the present invention with a thickness of 300 p is obtained by using the device of Figure 1 under the following operating conditions:
pump r.p.m. : 15 r.p.m. equivalent to a throughput of 18 cc/min size setting of filming extruder: 200 a dragging roller r.p.m.: 2.15 r.p.m.
temperature 1st bath (CaCl2 1~ w/v): 20'C
temperature 2nd bath (CaCl2 2~ w/v): 2'7'C
extruded film length produced per minute: 0.4 m.
Any active principle compatible with the gel composition, such as substances of antiseptic, antibiotic, anti-inflammatory, antihistaminic or other activity, can be incorporated into the gel either alone or in association. The concentration of the active principle incorporated into the gel depends on its pharmacological characteristics, and would represent a quantity such as to make it effective for the purpose of the specific application. The medicament quantity in the compositions of the invention.can vary from about O.Olx to 10~ of the weight of the final product.
The film obtained in this manner can be easily stored, handled and used advantageously as covering or medication material for cutaneous lesions and/or pathologies such as the treatment of wounds of surgical or traumatic origin, burns or lesions of pathological origin such as stasis ulcers, bedsores etc.
Some non-limiting examples of the preparation of self-supporting film according to the invention are described below.
24.5 g of sodium alginate are dispersed at ambient temperature in 250 ml of water under continuous stirring. A viscous gel forms, to which are added 1.4 g of sodium hyaluronate Hyalastine fraction (European patent EP 01385'j2 granted on 25th July 1990), 35 g of glycerol and ~ g of NaCl dissolved in 250 ml of water under stirring, the final solution volume then being adjusted to '700 ml.
Slow stirring, to avoid incorporating air, is then continued for about 20 hours, after which the viscous solution is filtered through a 20 a mesh filter and degassed under vacuum.
The solution is extruded by pumping through a slit of width 12 cm ~d of set thickness, and is coagulated by passing through two successive baths containing calcium chloride, the first at 20'C
with a concentration of lx and the next at 30~C with a concentration of 2x. The film obtained, having a thickness of about 0.250 mm, is wound on a suitable spool, washed by immersion in a water bath for 1 hour and finally stored in an aqueous solution containing 5x glycerol, 0.2x methylparaben, 0.02x propylparaben and 0.2x sodium dehydroacetate.
Following the procedure described in Example 1, 1.4 g of sodium hyaluronate Hyalectine fraction (European patent EP 01385'72 granted on 25th July 1990) are added in place of the Hyalastine fraction, to obtain a film having analogous characteristics to those of the film obtained in Example 1.
50 ml of an aqueous solution containing 0.4 g of hyaluronic acid ethyl ester of ~5x esterification (HYAFF ~ p~5 European patent application EPA 216453 of '7.x.86) are added to 150 ml of an ~o~~~~o aqueous solution containing 7 g of sodium alginate, 10 g of glycerol and 2 g of NaCl. After filtration and degassing, the final solution is extruded and coagulated by the procedure described in Example 1 to obtain 150 g of film with a thickness of 0.250 mm. The film is stored in the solution of glycerol and preservatives described in Example 1.
50 ml of an aqueous solution containing 5 g of polyethyleneglycol 1500 are added to 150 ml of an aqueous solution containing '7 g of ZO sodium alginate, 10 g of glycerol and 2 g of NaCl. After filtration and degassing, the final solution is extruded and coagulated by the procedure described in Example 1 to obtain 150 g of film with a thickness of 0.250 mm. The film is stored in the solution of glycerol and preservatives described in Example 1.
50 ml of an aqueous solution containing 2.5 g of p-(aminomethyl) benzenesulphonamide acetate are added to 150 ml of an aqueous solution containing ~ g of sodium alginate, 10 g of glycerol and 2 g of NaCl. After filtration and degassing, the final solution is extruded and coagulated by the procedure described in Example 1 to obtain 150 g of film with a thickness of 0.250 mm. The film is stored in the solution of glycerol and preservatives described in Example 1.
50 ml of an aqueous solution containing 0.1 g of the neomycin salt of hyaluronic acid partly esterified with ethanol ('75x of the carboxyl groups esterified with ethanol, 25x of the carboxyl 20434~~
groups esterified with neomycin in accordance with Example 29 of European patent application EPA 216453 filed on 7.7.1986) and 0.3 g of the 75% esterified partial ethyl ester of hyaluronic acid are added to 150 ml of an aqueous solution containing 7 g of sodium alginate, 10 g of glycerol and 2 g of NaCl. After filtration and degassing, the final solution is extruded and coagulated by the procedure described in Example 1 to obtain 150 g of film with a thickness of 0.250 mm. The film is stored in the solution of glycerol and preservatives described in Example 1. The final neomycin content of the Film is 0.00305 g/100 g.
50 ml of an aqueous dispersion of 10 g of microbeads obtained from mixed ethyl and hydrocortisone ester of hyaluronic acid (Example of European patent application EPA 216453 of 7.'7.86) are added 15 to 150 ml of an aqueous solution containing 7 g of sodium alginate, 10 g of glycerol and 2 g of NaCl. The final dispersion is extruded and coagulated by the procedure described in Example 1 to obtain 150 g of film with a thickness of 0.250 mm. The film is stored in the solution of glycerol and preservatives described in Example i.
To demonstrate the advantages and activity of the highly hydrated self-supporting film according to the present invention a trial was conducted using 45 male Sprague-Dawley rats of weight 225-250 g: The rats were divided into three groups and were given a heat lesion by a suitable instrument containing a metal prod of known area able to maintain a constant temperature. By applying this instrument to the back of the animal in a region close to the 2~43~50 io caudal reproducible heat lesions were obtained classifiable as third degree burns.
The treatment scheme involved a group of untreated animals, a group of animals treated conventionally with vaselin gauze and a third group treated with a film of hydrated gel as described in Example 1 of the present patent. The medications were changed every 3 days, 5 animals of each group being sacrificed 9, 15 and 25 days after the lesion. After a planimetric evaluation of the lesion area and eschar area, biopsies were taken for histological examination. The results of these tests are given in Table 1.
day 9 day 15 day 25 NT GG G NT GG G NT GG G
Persistence of eschar + + + + + * + * -Reduction in lesion area - - * - - + - * ++
Neoangiogenesis - - + - - ++ - - +++
NT = not treated; GG = vaselin gauze; G = gel film - = not apparent; * = hardly apparent; + = apparent; ++ = very apparent; +++ = extremely apparent The results summarized in the table show that burns treated with the composition described in Example 1 of the present patent have a positive effect on early eschar fall, reduction in lesion area and neovascularization.
50 ml of an aqueous dispersion of 10 g of microbeads obtained from mixed ethyl and hydrocortisone ester of hyaluronic acid (Example of European patent application EPA 216453 of 7.'7.86) are added 15 to 150 ml of an aqueous solution containing 7 g of sodium alginate, 10 g of glycerol and 2 g of NaCl. The final dispersion is extruded and coagulated by the procedure described in Example 1 to obtain 150 g of film with a thickness of 0.250 mm. The film is stored in the solution of glycerol and preservatives described in Example i.
To demonstrate the advantages and activity of the highly hydrated self-supporting film according to the present invention a trial was conducted using 45 male Sprague-Dawley rats of weight 225-250 g: The rats were divided into three groups and were given a heat lesion by a suitable instrument containing a metal prod of known area able to maintain a constant temperature. By applying this instrument to the back of the animal in a region close to the 2~43~50 io caudal reproducible heat lesions were obtained classifiable as third degree burns.
The treatment scheme involved a group of untreated animals, a group of animals treated conventionally with vaselin gauze and a third group treated with a film of hydrated gel as described in Example 1 of the present patent. The medications were changed every 3 days, 5 animals of each group being sacrificed 9, 15 and 25 days after the lesion. After a planimetric evaluation of the lesion area and eschar area, biopsies were taken for histological examination. The results of these tests are given in Table 1.
day 9 day 15 day 25 NT GG G NT GG G NT GG G
Persistence of eschar + + + + + * + * -Reduction in lesion area - - * - - + - * ++
Neoangiogenesis - - + - - ++ - - +++
NT = not treated; GG = vaselin gauze; G = gel film - = not apparent; * = hardly apparent; + = apparent; ++ = very apparent; +++ = extremely apparent The results summarized in the table show that burns treated with the composition described in Example 1 of the present patent have a positive effect on early eschar fall, reduction in lesion area and neovascularization.
Claims (21)
1. A gel in the form of a highly-hydrated self-supporting film containing a quantity of between 1% and 7.5% of one or more alkaline alginates and/or ammonium alginate, between 0.1% and 5% of alkaline earth alginate, between 0.1% and 10% of a polyalcohol and between 0.05% and 10% of a natural, synthetic or semisynthetic polymer having a hydrophilic character, the remaining component being water.
2. A gel in the form of a highly-hydrated self-supporting film as defined in claim 1, containing about
3.5% of one or more alkaline alginates and/or ammonium alginate.
3. A gel in the form of a highly-hydrated self-supporting film as defined in claim 1 or 2, in which the alkaline alginate is sodium alginate.
3. A gel in the form of a highly-hydrated self-supporting film as defined in claim 1 or 2, in which the alkaline alginate is sodium alginate.
4. A gel in the form of a highly-hydrated self-supporting film as defined in claim 1, 2 or 3, containing 1% of calcium alginate.
5. A gel in the form of a highly-hydrated self-supporting film as defined in any one of claims 1 to 4, containing about 5% of the polyalcohol.
6. A gel in the form of a highly-hydrated self-supporting film as defined in claim 5, in which the polyalcohol is glycerol.
7. A gel in the form of a highly-hydrated self-supporting film as defined in any one of claims 1 to 6, containing about 0.5% of the hydrophilic polymer.
8. A gel in the form of a highly-hydrated self-supporting film as defined in claim 7, in which the hydrophilic polymer is sodium hyaluronate.
9. A gel in the form of a highly-hydrated self-supporting film as defined in any one of claims 1 to 8, including a medicament.
10. A process for preparing a gel in the form of a highly-hydrated self-supporting film, in which an initial fluid gel containing one or more alkaline alginates and/or ammonium alginate, an alkaline earth alginate, a polyalcohol, a natural, synthetic or semisynthetic polymer having a hydrophilic character, and water, is extruded by being pumped through a slit of variable width and thickness, and is coagulated by passage through between 2 and 4 successive coagulation baths having a Ca2+ ion concentration of between 0.1% and 10% and a temperature of between 15°C and 40°C.
11. A process as defined in claim 10, in which the initial fluid gel contains a quantity of between 3.5% and 7.5% of one or more alkaline alginates and/or ammonium alginate, a quantity of between 0.1% and 5% of an alkaline earth alginate, a quantity of between 0.5% and 7.5% of a polyalcohol, and a quantity between 0.1% and 10% of the polymer having a hydrophilic character, the remaining component being water.
12. A process as defined in claim 11, in which the alkaline alginate and/or ammonium alginate content is about 3.5%.
13. A process as defined in claim 12, in which the alkaline alginate is sodium alginate.
14. A process as defined in claim 11, 12 or 13, in which the polyalcohol content is about 5%.
15. A process as defined in claim 14, in which the polyalcohol is glycerol.
16. A process as defined in any one of claims 11 to 15, in which the hydrophilic polymer content is about 0.2%.
17. A process as defined in claim 16, in which the hydrophilic polymer is sodium hyaluronate.
18. A process as defined in any one of claims 11 to 17, in which the Ca2+ ion concentration is about 1% in the first bath and about 2% in the subsequent baths.
19. A process as defined in any one of claims 11 to 18, in which the temperature is about 20°C in the first bath and about 30°C in the subsequent baths.
20. A process as defined in any one of claims 11 to 19, in which two coagulation baths are provided.
21. Use of a gel in highly-hydrated self-supporting film form as defined in any one of claims 1 to 9, for treating cutaneous lesions and/or pathologies.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT20477 | 1990-05-30 | ||
IT02047790A IT1248666B (en) | 1990-05-30 | 1990-05-30 | GEL IN THE FORM OF HIGHLY HYDRATED SELF-SUPPORTING FILMS, PROCESS FOR THEIR PREPARATION AND USE IN THE THERAPY OF INJURIES AND / OR SKIN PATHOLOGIES |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2043450A1 CA2043450A1 (en) | 1991-12-01 |
CA2043450C true CA2043450C (en) | 2001-12-18 |
Family
ID=11167535
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002043450A Expired - Lifetime CA2043450C (en) | 1990-05-30 | 1991-05-29 | Gels in the form of highly hydrated self-supporting film, the process for their preparation, and their use in therapy of cutaneous lesions and/or pathologies |
Country Status (22)
Country | Link |
---|---|
US (3) | US5523093A (en) |
EP (1) | EP0459378B1 (en) |
JP (1) | JP2960204B2 (en) |
KR (1) | KR0184884B1 (en) |
AT (1) | ATE141520T1 (en) |
AU (1) | AU7806791A (en) |
BR (1) | BR9102226A (en) |
CA (1) | CA2043450C (en) |
DE (1) | DE69121471T2 (en) |
DK (1) | DK0459378T3 (en) |
ES (1) | ES2093654T3 (en) |
FI (1) | FI104148B (en) |
GR (1) | GR3021259T3 (en) |
HU (1) | HU208069B (en) |
IE (1) | IE75717B1 (en) |
IL (1) | IL98254A (en) |
IN (1) | IN172300B (en) |
IT (1) | IT1248666B (en) |
NO (1) | NO304402B1 (en) |
PT (1) | PT97801B (en) |
SG (1) | SG49080A1 (en) |
ZA (1) | ZA914041B (en) |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1260154B (en) * | 1992-07-03 | 1996-03-28 | Lanfranco Callegaro | HYALURONIC ACID AND ITS DERIVATIVES IN INTERPENETRATING POLYMERS (IPN) |
GB9218749D0 (en) * | 1992-09-04 | 1992-10-21 | Courtaulds Plc | Alginate gels |
GB2275685B (en) * | 1993-03-03 | 1997-04-30 | Johnson & Johnson Medical | Water soluble wound dressing materials |
GB2275686B (en) * | 1993-03-03 | 1997-04-30 | Johnson & Johnson Medical | Swellable wound dressing materials |
GB9414303D0 (en) * | 1994-07-15 | 1994-09-07 | C V Lab Ltd | Alginate fibres, method of preparation and use |
GB2291348B (en) * | 1994-07-18 | 1999-01-20 | Johnson & Johnson Medical | Sterile gel composition for wound treatment comprising alginate and polyhydric alcohol |
ES2221931T3 (en) * | 1994-10-28 | 2005-01-16 | Advanced Medical Solutions Limited | DEHYDRATED HYDROGELS. |
US5621093A (en) * | 1995-06-06 | 1997-04-15 | Anika Research, Inc. | Steam-sterilizing solid hyaluronic acid |
GB9514361D0 (en) * | 1995-07-13 | 1995-09-13 | Bristol Myers Squibb Co | A film for topical use in the treatment of wounds |
JPH11509442A (en) * | 1995-07-19 | 1999-08-24 | イノベイティブ・テクノロジーズ・リミテッド | Wound treatment composition |
GB9522314D0 (en) * | 1995-11-01 | 1996-01-03 | Bristol Myers Squibb Co | Water soluble films |
GB9608222D0 (en) * | 1996-04-20 | 1996-06-26 | Innovative Tech Ltd | Dehydrated hydrogels |
US6060534A (en) | 1996-07-11 | 2000-05-09 | Scimed Life Systems, Inc. | Medical devices comprising ionically and non-ionically crosslinked polymer hydrogels having improved mechanical properties |
US6281341B1 (en) * | 1997-04-30 | 2001-08-28 | Biomm, Inc. & University Of Miami | Hetero-polysaccharide conjugate and methods of making and using the same |
US5976150A (en) * | 1998-08-25 | 1999-11-02 | Alcon Laboratories, Inc. | Intraocular lens injection system |
AU2002224523B2 (en) | 2000-07-21 | 2007-01-25 | Mark B. Lyles | Sunscreen formulations containing nucleic acids |
JP3834215B2 (en) | 2001-09-07 | 2006-10-18 | アグリテクノ矢崎株式会社 | Gel coated seeds |
KR100433363B1 (en) * | 2002-04-15 | 2004-05-28 | 주식회사 동구제약 | Epidermal hydrogel formulation containing acyclovir |
WO2004073697A1 (en) * | 2003-02-18 | 2004-09-02 | Scherr George H | Alginate foam compositions |
HUP0303313A2 (en) * | 2003-10-09 | 2005-07-28 | Richter Gedeon Vegyészeti Gyár Rt. | Transdermal pharmaceutical compositions |
US20110071448A1 (en) * | 2004-06-24 | 2011-03-24 | Ezio Margiotta | Liquid impermeable material |
SE530184C2 (en) * | 2005-12-23 | 2008-03-18 | Kjell Stenberg | Bioadhesive pharmaceutical film composition containing low viscous alginates |
US8668863B2 (en) | 2008-02-26 | 2014-03-11 | Board Of Regents, The University Of Texas System | Dendritic macroporous hydrogels prepared by crystal templating |
JP5435723B2 (en) * | 2009-01-26 | 2014-03-05 | 公益財団法人北九州産業学術推進機構 | Method for producing alginic acid molded article |
FR2942242B1 (en) * | 2009-02-17 | 2011-06-03 | Laboratoire Tetra Medical | PROCESS FOR OBTAINING A LONGIFORM ELEMENT OF POLYSACCHARIDE, IN PARTICULAR A CHITOSAN YARN AND POLYSACCHARIDE YARN OBTAINED |
WO2010117266A1 (en) * | 2009-04-06 | 2010-10-14 | Broockeville Corporation N.V. | In situ gelling alginate systems |
JP5724356B2 (en) | 2010-01-19 | 2015-05-27 | 株式会社リコー | Conveying apparatus, image forming apparatus, and program |
JP2012035233A (en) * | 2010-08-11 | 2012-02-23 | Seiko Epson Corp | Gel forming solution and method for producing gel |
WO2012048283A1 (en) | 2010-10-08 | 2012-04-12 | Board Of Regents, The University Of Texas System | One-step processing of hydrogels for mechanically robust and chemically desired features |
EP2624874A4 (en) | 2010-10-08 | 2014-04-02 | Univ Texas | Anti-adhesive barrier membrane using alginate and hyaluronic acid for biomedical applications |
US11565027B2 (en) | 2012-12-11 | 2023-01-31 | Board Of Regents, The University Of Texas System | Hydrogel membrane for adhesion prevention |
KR102212023B1 (en) * | 2013-07-03 | 2021-02-05 | 가부시키가이샤 리타파마 | Water-soluble hyaluronic acid gel and method for producing same |
CZ2014451A3 (en) | 2014-06-30 | 2016-01-13 | Contipro Pharma A.S. | Antitumor composition based on hyaluronic acid and inorganic nanoparticles, process of its preparation and use |
CZ309295B6 (en) * | 2015-03-09 | 2022-08-10 | Contipro A.S. | Self-supporting, biodegradable film based on hydrophobized hyaluronic acid, method of its preparation and use |
DE102015226167A1 (en) * | 2015-12-21 | 2017-06-22 | Henkel Ag & Co. Kgaa | Hair treatment kit with skin protection |
KR102278232B1 (en) | 2018-07-04 | 2021-07-15 | 주식회사 엘지화학 | Composition and wound dressings comprising the same |
CN109337130B (en) * | 2018-09-29 | 2021-03-30 | 青岛大学 | Preparation of polysaccharide polyelectrolyte self-supporting film and self-supporting film obtained by preparation |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB492264A (en) * | 1937-03-13 | 1938-09-13 | Cyril Wilfred Bonniksen | Improvements in or relating to the production of films of alginic material |
US2512616A (en) * | 1946-01-12 | 1950-06-27 | Johnson & Johnson | Hemostatic alginic surgical dressings |
GB1329693A (en) * | 1969-09-27 | 1973-09-12 | Wallace Cameron Co Ltd | Haemostatic surgical dressing and a method of manaufacturing same |
US3640741A (en) * | 1970-02-24 | 1972-02-08 | Hollister Inc | Composition containing gel |
US4391799A (en) * | 1980-02-15 | 1983-07-05 | The United States Of America As Represented By The Secretary Of The Army | Protective gel composition for treating white phosphorus burn wounds |
EP0065376B1 (en) * | 1981-05-11 | 1985-08-14 | TATE & LYLE PUBLIC LIMITED COMPANY | Immobilized enzymes |
JPS58206751A (en) * | 1982-05-26 | 1983-12-02 | 日石三菱株式会社 | Wound covering material |
US4554166A (en) * | 1984-03-15 | 1985-11-19 | General Foods Corporation | Extrusion process for shrimp or crabmeat analog products in a series of non-boiling gelling baths |
DE3704907A1 (en) * | 1987-02-17 | 1988-08-25 | Bayer Ag | TOPICALLY APPLICABLE PREPARATIONS OF GYRASE INHIBITORS IN COMBINATION WITH CORTICOSTEROIDS |
US5071741A (en) * | 1988-04-18 | 1991-12-10 | Cryolife, Inc. | Cryoprotective agent and its use in cryopreservation of cellular matter |
FR2636339B1 (en) * | 1988-09-09 | 1992-07-17 | Auge Pier | AQUEOUS GEL BASED ON HYALURONIC ACID AND DEOXYRIBONUCLEIC ACID FOR USE IN COSMETICS, AND PREPARATION METHOD |
US4948575A (en) * | 1989-01-24 | 1990-08-14 | Minnesota Mining And Manufacturing Company | Alginate hydrogel foam wound dressing |
-
1990
- 1990-05-30 IT IT02047790A patent/IT1248666B/en active IP Right Grant
-
1991
- 1991-05-24 IL IL98254A patent/IL98254A/en not_active IP Right Cessation
- 1991-05-28 DE DE69121471T patent/DE69121471T2/en not_active Expired - Lifetime
- 1991-05-28 ES ES91108656T patent/ES2093654T3/en not_active Expired - Lifetime
- 1991-05-28 EP EP91108656A patent/EP0459378B1/en not_active Expired - Lifetime
- 1991-05-28 SG SG1996005842A patent/SG49080A1/en unknown
- 1991-05-28 DK DK91108656.9T patent/DK0459378T3/en active
- 1991-05-28 AT AT91108656T patent/ATE141520T1/en not_active IP Right Cessation
- 1991-05-28 ZA ZA914041A patent/ZA914041B/en unknown
- 1991-05-28 IE IE182491A patent/IE75717B1/en not_active IP Right Cessation
- 1991-05-29 JP JP3125956A patent/JP2960204B2/en not_active Expired - Lifetime
- 1991-05-29 NO NO912057A patent/NO304402B1/en not_active IP Right Cessation
- 1991-05-29 PT PT97801A patent/PT97801B/en not_active IP Right Cessation
- 1991-05-29 BR BR919102226A patent/BR9102226A/en not_active Application Discontinuation
- 1991-05-29 HU HU911792A patent/HU208069B/en unknown
- 1991-05-29 FI FI912573A patent/FI104148B/en active
- 1991-05-29 CA CA002043450A patent/CA2043450C/en not_active Expired - Lifetime
- 1991-05-30 KR KR1019910008914A patent/KR0184884B1/en not_active IP Right Cessation
- 1991-05-30 AU AU78067/91A patent/AU7806791A/en not_active Abandoned
- 1991-05-30 US US07/707,790 patent/US5523093A/en not_active Expired - Lifetime
- 1991-05-30 IN IN409CA1991 patent/IN172300B/en unknown
-
1995
- 1995-06-07 US US08/476,569 patent/US5709877A/en not_active Expired - Lifetime
- 1995-06-07 US US08/488,049 patent/US5618561A/en not_active Expired - Lifetime
-
1996
- 1996-10-04 GR GR960402610T patent/GR3021259T3/en unknown
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