Process and apparatus for manufacturing foam dressings, foam dressings made therefrom, and composition and process of preparing foam precursor mixtures

Abstract

Process for manufacturing foam dressing comprises compounding a foam precursor mixture, the foam precursor mixture comprising a matrix-forming material and a biomaterial. Supercritical carbon dioxide is mixed with the foam precursor mixture to form a foam block that is passed through an extrusion die to form a foam slab. The foam slab is calendered to obtain a foam dressing. Process for preparing a foam precursor mixture for use in manufacturing a foam dressing comprises mixing a matrix-forming material and a biomaterial to form an initial mixture and drying the initial mixture to substantially remove moisture therefrom, thereby obtaining the foam precursor mixture.

Description

PROCESS AND APPARATUS FOR MANUFACTURING FOAM DRESSINGS, FOAM DRESSINGS MADE THEREFROM, AND COMPOSITION AND PROCESS OF PREPARING FOAM PRECURSOR MIXTURESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 620,224, filed on January 12, 2024, which is incorporated herein by reference in its entirety.BACKGROUND

[0002] A wide variety of compositions, materials, and devices are known in the art for use in treating wounds and tissue disruptions. Wounds may be the result of trauma, surgery, or disease and may require measures to control bleeding, absorb wound exudate, ease pain, assist in debridement, and protection from infection or escalating infection. Such measures aim to promote healing and offer protection from further damage. Commonly, a wound dressing is used to protect the wound from external contaminants, absorb exudate, and provide favorable conditions for healing.

[0003] While there are various types of wound dressings available, foam dressings have been found to be particularly useful for healing chronic wounds. Foam dressings can absorb moderate to high amounts of exudate and provide a suitably moist environment with cushioning effect. They are typically made from a polymeric base material that forms a foam that is permeable to gases and water vapors. Foam dressings may be used in combination with biomaterials, such as oxidized regenerated cellulose (ORC), collagen, hyaluron, etc., and other agents such as antimicrobial agents, enzymatic debriders, and the like.

[0004] Conventionally, foam dressings containing collagen and oxidized regenerated cellulose (ORC) are made via a non-continuous freeze-drying process. Due to the non-continuous nature of the process, it is time consuming and labor intensive and hence expensive. Furthermore, freeze drying requires a water-based formulation, which limits the variety of raw materials that can be used to water soluble or at least water compatible materials.SUMMARY

[0005] In one embodiment, a process and apparatus for manufacturing foam dressings and foam dressings made therefrom are described. In one embodiment, a composition and process of preparing foam precursor mixture are described. The various embodiments described herein allow for continuous manufacture of foam dressings.

[0006] In one embodiment, a method for manufacturing foam dressings comprises: compounding a foam precursor mixture, the foam precursor mixture comprising a matrix-forming material and a biomaterial; mixing supercritical carbon dioxide with the foam precursor mixture to form a foam block;passing the foam block through an extrusion die to form a foam slab; and calendering the foam slab to obtain a foam dressing.

[0007] In one embodiment an apparatus for manufacturing foam dressings comprises: a dynamic mixer to compound a foam precursor mixture, the foam precursor mixture comprising a matrix-forming material and a biomaterial; a fluid reservoir to store, at a predetermined pressure and temperature, liquefied carbon dioxide and supply carbon dioxide for mixing with the foam precursor mixture; a static mixer in fluid communication with the outlet of the dynamic mixer, wherein the static mixer is to mix the foam precursor mixture received from the dynamic mixer and the carbon dioxide to form a foam block; an extrusion die in fluid communication with an outlet of the static mixer to form a foam slab from the foam block; and a rolling unit in fluid communication with an outlet of the extrusion die for calendering the foam slab to obtain a foam dressing.

[0008] In one embodiment, a composition of a foam precursor mixture for use in manufacturing a foam dressing comprises: a matrix-forming material; and a biomaterial, wherein the matrix-forming material and the biomaterial are present in a ratio that allows for the formation of a foam block when subjected to a foam production process with supercritical carbon dioxide.

[0009] In one embodiment, a method for preparing a foam precursor mixture for use in manufacturing a foam dressing comprises: providing a matrix-forming material; providing a biomaterial; mixing the matrix-forming material and the biomaterial to form an initial mixture; and drying the initial mixture to substantially remove moisture therefrom, thereby obtaining the foam precursor mixture.BRIEF DESCRIPTION OF DRAWINGS

[0010] The disclosure may be understood in consideration of the following detailed description of various embodiments of the disclosure in connection with the accompanying figures, in which:

[0011] FIG. 1 is an example process of manufacturing foam dressing.

[0012] FIGs. 2a and 2b are example illustrations of an apparatus for manufacturing foam dressing.

[0013] FIG. 3 is an example process of manufacturing foam precursor mixture.DETAILED DESCRIPTION

[0014] Described herein are processes and apparatus for manufacturing foam dressings and foam dressings made therefrom, and compositions and processes of preparing foam precursor mixture. The various embodiments described herein allow for continuous manufacture of foam dressings. Further, the processes are not aqueous based and hence allow for the use of additives that are not water based or not water compatible in addition to the conventionally used water soluble and water compatible additives.Definitions

[0015] As used herein, “about” means ± 10 percent of a given value. For example, about 10 means 9 to 11.

[0016] As used herein, “collagen” refers to a structural protein found in, for example: (Type I): skin, tendon, vasculature, organs, bone (Type II): cartilage (Type III): reticulate(Type IV): basal lamina, epithelium-secreted layer of the basement membrane(Type V): cell surfaces, hair, and placenta

[0017] As used herein, “drying” or “predry” refers to the removal of volatile or vaporizable compounds. When a substance herein is described as substantially “dried,” it means that less than about 5 wt% of said compounds are present. Various methods of drying are known to a skilled artisan.

[0018] As used herein, “foam” refers to soft, light weight, high volume, low density, porous stmcture.

[0019] As used herein, the terms “block” and “slab” are used to denote a continuous structure of any cross-section where the length is greater than the width and height, and are not restricted to any specific shape.

[0020] As used herein, “exclude” means that a component is absent (i.e., present in 0 wt%).

[0021] As used herein, “microorganism” or “microbe” refers to bacteria, yeast, mold, fungi, protozoa, mycoplasma, and / or viruses including lipid-enveloped RNA and DNA viruses.

[0022] As used herein, “oxidized regenerated cellulose” or “ORC” refers to a regenerated cellulose wherein at least some portion of hydroxyl groups have been oxidized (e.g., -OH a -CO2H). Cellulose is a polymeric structural framework of plant cells, with repeating units of d-glucose. Due to the presence of strong hydrogen bonding between polymer chains, cellulose is insoluble in common solvents, including insoluble in water. Regenerated cellulose is a class of materials derived from natural cellulose, wherein the natural cellulose has undergone a chemical manufacturing process that breaks down cellulose such that it may solubilized, functionalized, thereby “regenerated,” and extruded into a useful fiber. The hydroxyl groups in cellulose can be functionalized to form ethers, esters, acids, amides, and the like.

[0023] As used herein, “polymer” refers to a substance having one or more repeating monomer units. The chemical identities of the polymeric substances herein are at times described in terms of the monomers to which the polymer is derived. A skilled artisan would readily understand the reactivity profde of the recited monomers and how the monomers could synthetically be joined to form the polymer.

[0024] As used herein, “liquified carbon dioxide” refers to highly compressed and cooled carbon dioxide present in a liquid state. Since the phase diagram triple point of carbon dioxide is at about 31°C and about 73 bar, below 31°C and at sufficient pressure, carbon dioxide is liquid state (density around lg / cm3). Thus, carbon dioxide can be in a liquid state when stored at room temperature in a pressure cylinder and is referred to as liquefied carbon dioxide.

[0025] As used herein, “supercritical carbon dioxide” refers to carbon dioxide held at or above its critical temperature and critical pressure. For example, above 31°C and at sufficient pressure carbon dioxide is in a supercritical state (density around 0.2 to 0.9 gm / cm3 depending on pressure). Thus, when liquefied carbon dioxide is injected into a mixer at temperatures greater than 31°C, its state changes to a supercritical state.

[0026] As used herein, the term “wound” refers to broken skin, e.g., a cut, a puncture, an abrasion, a scratch, a rash, and the like. A “wound dressing” refers to an article that may control bleeding, absorb wound exudate, ease pain, assist in debriding, protect against infection, mediate infection, modulate proteases, or otherwise promote healing and protection from further damage. A “chronic wound” refers to a wound that does not progress through a normal, orderly, or timely sequence of repair, e.g., a wound that does not heal after 4 weeks of standard care.PROCESS FOR MANUFACTURING FOAM DRESSINGS AND FOAM DRESSINGS MADE THEREFROM

[0027] FIG. 1 depicts an example process 100 of manufacturing foam dressing. The various steps of process 100 may be carried out at a temperature in a range of 60-160°C, preferably at a temperature in a range of 80-160°C, and more preferably at a temperature in a range of 80-140°C. It will be understood that the temperature at different stages may be different and optionally, suitable heating / cooling mechanisms may be used at different stages for maintaining the desired temperature at that stage as will be easily understood by a person skilled in the art though such heating / cooling mechanism may not have been specifically described herein.

[0028] At step 102, a foam precursor mixture is compounded, for example, using a dynamic mixer. The foam precursor mixture comprises a matrix-forming material and a biomaterial. Compounding helps to uniformly mix and homogenize the foam precursor mixture.

[0029] In one example, the matrix-forming material comprises at least one of polyvinylpyrrolidone (PVP), lipids, polyvinylacetate (PVA), and polyethylene glycol. In one example, the biomaterial comprises at least one of collagen (type I, II, III), alginate, oxidized regenerated cellulose (ORC), and hyaluron. In one example, the foam precursor mixture comprises 60% to 99% by weight of the matrixforming material and 1% to 25% by weight of the biomaterial. In one example, the foam precursor mixture comprises 70% to 95% by weight of the matrix-forming material and 5% to 10% by weight of the biomaterial.

[0030] In one example, the foam precursor mixture further comprises 0.01% to 5% by weight of an antimicrobial material and preferably 0.05% to 1% by weight of an antimicrobial material. The antimicrobial material comprises one or more of: benzalkonium chloride (BAC), tetracycline, penicillins, terramycins, erythromycin, bacitracin, neomycin, polymycin B, mupirocin, clindamycin, colloidal silver, silver salts, silver sulfadiazine, chlorhexidine, povidone iodine, triclosan, sucralfate, quaternary ammonium salts, potassium chloride (KCI), Chitosan, Chlorhexidine gluconate, and metals selected from silver, copper, or zinc.

[0031] In one example, the foam precursor mixture further comprises 1% to 30% by weight of an additive. The additive comprises one or more of: pH adjusting agents, buffers, a mono-ol, and a polyol. The buffers may be, for example, citric acid / citrate buffer or the like. The polyols may be, for example, glycerol, 1,2-octanediol, triols. It will be understood that other suitable additives may also be used.

[0032] At step 104, supercritical carbon dioxide is mixed with the compounded foam precursor mixture, for example, in a static mixer, to form a foam block. For this, in one example, liquefied carbon dioxide may be injected into the static mixer at a pressure of at least 74 bar and a temperature of at least 60°C. Liquefied carbon dioxide is carbon dioxide gas that is highly compressed and cooled to a liquid form. On injection of liquefied carbon dioxide into the compounded foam precursor mixture, its state changes to a supercritical state due to the higher temperature of the mixture. The supercritical carbon dioxide mixes with the compounded foam precursor mixture. Further, as mixing progresses and pressure reduces, the phase of carbon dioxide changes to a gaseous state. As the carbon dioxide gas escapes, it causes bubble / pore formation that causes the foam precursor mixture to rise resulting in a substantially dry porous structure referred to as foam block.

[0033] At step 106, the foam block is passed through an extmsion die to form a foam slab. The extrusion die channels the foam block under pressure to impart specific cross-sectional shapes. For example, the foam slab thus formed may have a rectangular, oval, trapezoidal, or any other suitable cross-sectional shape.

[0034] At step 108, the foam slab is calendered to obtain a foam dressing. During calendering, the foam slab is passed through two rolls rotating in opposite directions. The rolls are spaced apart by a distance corresponding to the desired thickness of the foam dressing to be formed. In one example, the calendering comprises laminating upper and lower surfaces of the foam slab with upper and lower liner films. In one example, the edges of the upper and lower liner films may be sealed for reduced moisture absorption during storage and transport. The sealing may be performed by heat sealing or any other suitable process. In one example, the foam dressing thus formed may be suitably cut into smaller pieces and packaged for sale.

[0035] In one example, the foam dressing formed by the process 100 has a solid content of 10- 30% by volume, preferably 20-25% by volume.

[0036] As can be understood, the process 100 can be carried out as a continuous process, for example, using an extrusion manufacturing set-up. As a result, the cost and time of production are reduced and the lead time for manufacture is substantially reduced. Further, the process can use substantially dried foam precursor mixture. Hence, it allows for the use of additives that are not water based or not water compatible in addition to the conventionally used water soluble and water compatible additives. This increases the variety of additives that may be used to enhance wound healing and improve application of the foam dressing.APPARATUS FOR MANUFACTURING FOAM DRESSINGS

[0037] FIGs. 2a and 2b are example illustrations of an apparatus for manufacturing foam dressing, for example, by the process 100 as discussed above with reference to FIG. 1.

[0038] As shown in the block diagram Fig. 2a, apparatus 200 includes a dynamic mixer 202 to receive and compound a foam precursor mixture, the foam precursor mixture comprising a matrixforming material and a biomaterial as discussed above. The foam precursor mixture may optionally include antimicrobial material and / or additives, as discussed above. The dynamic mixer 202 may be one of: a single-screw coextruder and a multi-screw coextruder.

[0039] Further, a fluid reservoir 204 is to store, at a predetermined pressure and temperature, liquefied carbon dioxide and supply carbon dioxide for mixing with compounded foam precursor mixture. Also, a static mixer 206 is in fluid communication with the outlet of the dynamic mixer 202. The static mixer 206 is to mix the foam precursor mixture received from the dynamic mixer 202 and the carbon dioxide received from the fluid reservoir 204 to form a foam block. The carbon dioxide may be injected at an outlet of the dynamic mixer 202 or an inlet of the static mixer 206. On injection, the liquefied carbon dioxide converts to supercritical carbon dioxide, which further converts to gaseous carbon dioxide as the mixing proceeds, thereby causing the formation of the porous foam block.

[0040] An extrusion die 208 is in fluid communication with an outlet of the static mixer 206 to form a foam slab from the foam block by channeling the foam block through the die passage. Further, a rolling unit 210 is in fluid communication with an outlet of the extrusion die 208 for calendering the foam slab to obtain a foam dressing. The rolling unit may include a pair of rolls spaced apart from each other to compress the foam block to a desired thickness.

[0041] In one example, a drying unit 212 may be optionally used to predry the foam precursor mixture to substantially remove moisture therefrom, before the foam precursor mixture is supplied to the dynamic mixer 202. The drying unit may be any suitable drier, such as an oven or air drier or vacuum drier, usable to remove volatile compounds, particularly water and solvents, from the foam precursor mixture prior to compounding. The amount of water and / or solvents to be retained in the foam precursor mixture after drying may be suitably varied depending on the desired properties (such as stickiness and consistency) of the foam dressing to be formed.

[0042] In one example, liner supply units 214 may be used to supply upper and lower liner films to the rolling unit 210 to laminate upper and lower surfaces of the foam slab during calendering. Further, a sealing unit 216 may be used to seal edges of the upper and lower liner films upon lamination. The sealing techniques used may include heat sealing, taping down edges, or other suitable sealing techniques. The sealing may help prevent the absorption of ambient moisture by the foam dressing.

[0043] Fig. 2b illustrates an example set-up of the apparatus 200 discussed above. As shown in the figure, the apparatus 200 may be implemented as a continuous extrusion set-up. As discussed with reference to FIG. 1, though not shown, the apparatus 200 may include other units, such as heating / cooling units for maintaining temperature, pressure control units, etc.

[0044] The dynamic mixer 202 may be a screw type extruder that receives and compounds the foam precursor mixture and pushes the compounded foam precursor mixture towards the static mixer 206. The foam precursor mixture may have been optionally pre-dried before being sent to the dynamic mixer 202. The fluid reservoir 204 (not shown in this figure) may be in fluid communication with an outlet of the dynamic mixer 202 (or inlet of static mixer 206) via an injection mechanism to inject liquefied carbon dioxide into the compounded foam precursor mixture. As is understood, the liquified carbon dioxide changes state to supercritical carbon dioxide upon injection due to the higher temperature of the compounded foam precursor mixture.

[0045] The static mixer 206 may be a mixer with internal screws / baffles / undulations that cause mixing of the carbon dioxide and compounded foam precursor mixture as they pass through the static mixer 206. As is understood, the dynamic mixer 202 has moving parts, such as screws, while the static mixer 206 does not have moving parts. The mix of carbon dioxide and the compounded foam precursor mixture passes through the static mixer 206 due to the downstream pressure created by the dynamic mixer 202, which pushes the mix stream forward. As the mixing continues in the static mixer 206, the supercritical carbon dioxide changes state to gaseous carbon dioxide which bubbles through the mix stream causing it to rise and forming a porous foam block.

[0046] Further, the extmsion die 208 receives the foam block and channelizes it into a specific cross-sectional shape to form the foam slab. The cross-sectional shape of the foam slab depends on the cross-section of the extrusion die 208 used and may be, for example, rectangular, square, oval, trapezoidal, etc. The foam slab then undergoes calendering in the rolling unit 210, which includes the rolls 210-1 and 210-2. The rolls 210-1 and 210-2 are spaced apart by a distance corresponding to the desired thickness of the foam dressing to be formed. In one example, the calendering comprises laminating upper and lower surfaces of the foam slab with upper and lower liner films supplied to the rolling unit 210. The upper and lower liner films may be any suitable polymeric water-resistant liner film that can protect the foam dressing from ambient moisture. Optionally, the edges of the liner films may be sealed, for example, by heat sealing or taping down.

[0047] Thus, a continuous manufacturing process and apparatus set-up can be used for manufacturing the foam dressing of the present disclosure. The apparatus is a simple set-up and does not use harsh process conditions. Hence, the overall complexity and cost of production is reduced. Moreover, the extrusion process comprising the dynamic and static mixing provides high efficiency mixing with better homogenization. Hence, higher flexibility is obtained in raw material choice. Further, as discussed, the foam dressing can be continuously manufactured as opposed to batch manufacturing techniques used currently.PROCESS OF PREPARING A FOAM PRECURSOR MIXTURE AND COMPOSITIONTHEREOF

[0048] FIG. 3 depicts an example process 300 of manufacturing foam precursor mixture. The foam precursor mixture thus produced may be used to manufacture foam, for example, using the process 100 and / or apparatus 200 as described above.

[0049] At step 302, a matrix-forming material is provided. At step 304, a biomaterial is provided. The matrix-forming material and biomaterial provided may be solutions, such as aqueous solutions, or may be substantially dry. At step 306, the matrix-forming material and the biomaterial are mixed to form an initial mixture.

[0050] In one example, the matrix-forming material is added in an amount of 60% to 99% by weight of the foam precursor mixture and the biomaterial is added in an amount of 1% to 25% by weight of the foam precursor mixture. In another example, the matrix-forming material is in an amount of 70% to 95% by weight of the foam precursor mixture and the biomaterial is added in an amount of 5% to 10% by weight of the foam precursor mixture.

[0051] The matrix-forming material comprises at least one of polyvinylpyrrolidone (PVP), lipids, polyvinylacetate (PVA), and polyethylene glycol, and the biomaterial comprises at least one of collagen (type I, II, III), alginate, oxidized regenerated cellulose (ORC), and hyaluron.

[0052] In one example, an antimicrobial material is added to at least one of: the matrix-forming material, the biomaterial, and the initial mixture. The antimicrobial material may be added in an amount of 0.01% to 5% by weight of the foam precursor mixture, and preferably in an amount of 0.05% to 1% by weight of the foam precursor mixture. The antimicrobial material comprises one or more of benzalkonium chloride (BAC), tetracycline, penicillins, terramycins, erythromycin, bacitracin, neomycin, polymycin B, mupirocin, clindamycin, colloidal silver, silver salts, silver sulfadiazine, chlorhexidine, povidone iodine, triclosan, sucralfate, quaternary ammonium salts, potassium chloride (KCI), Chitosan, Chlorhexidine gluconate, and metals selected from silver, copper, or zinc.

[0053] In one example, at least one additive selected from the group consisting of pH adjusting agents, buffers, mono-ol, or polyol, is added to at least one of: the matrix-forming material, the biomaterial, and the initial mixture. The additive may be added in an amount of 1% to 30% by weight of the foam precursor mixture.

[0054] At step 308, the initial mixture is dried to substantially remove moisture and other solvents therefrom, thereby obtaining the foam precursor mixture. The drying may be performed at a temperature and for a duration sufficient to reduce the moisture content to a predetermined level suitable for subsequent foam formation. The amount of water and / or solvents to be retained in the foam precursor mixture after drying may be suitably varied depending on the desired properties (such as stickiness and consistency) of the foam dressing to be formed.

[0055] The foam precursor mixture / composition thus obtained may be used for manufacturing a foam dressing, for example as described above with reference to Fig. 1 and Figs. 2a-2b.

[0056] In one example, a foam precursor composition for use in manufacturing a foam dressing comprises a matrix-forming material and biomaterial, wherein the matrix-forming material and the biomaterial are present in a ratio that allows for the formation of a foam block when subjected to a foam production process with supercritical carbon dioxide. In one example, the matrix-forming material is present in an amount of 60% to 99% by weight, preferably 70-95% by weight, and the biomaterial is present in an amount of 1% to 25% by weight, preferably 5% to 10% by weight of the foam precursor composition.

[0057] The matrix-forming material may be selected from the group consisting of polyvinylpyrrolidone (PVP), lipids, polyvinylacetate (PVA), and polyethylene glycol, preferably is polyvinylpyrrolidone (PVP), and the biomaterial comprises at least one of collagen (type I, II, III), alginate, oxidized regenerated cellulose (ORC), and hyaluron, preferably is a mixture of collagen and oxidized regenerated cellulose. The collagen is selected from the group consisting of bovine collagen, porcine collagen, human collagen, equine collagen, fish collagen, recombinant collagen, or a combination thereof, preferably is selected from bovine collagen, porcine collagen, human collagen, or combinations thereof, more preferably is bovine collagen.

[0058] In one example, the foam precursor composition comprises an antimicrobial material in an amount of 0.01% to 5% by weight and preferably 0.05% to 1% by weight of the foam precursor composition. In one example, the foam precursor composition comprises an additive selected from the group consisting of pH adjusting agents, buffers, mono-ol, or polyol, in an amount of 1% to 30% by weight.

[0059] In various embodiments, a method of healing a wound is described. The method may include contacting a wound with a foam dressing of the present disclosure.EQUIVALENTS

[0060] Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific embodiments described specifically herein. Such equivalents are intended to be encompassed in the scope of the following claims.EXAMPLES

[0061] Objects and advantages of this disclosure are further illustrated by the following examples, but the particular materials and amounts thereof recited in these examples, as well as other conditions and details, should not be construed to unduly limit this disclosure. These examples are merely for illustrative purposes only and are not meant to be limiting on the scope of the appended claims.

[0062] For the purpose of testing the feasibility of forming a foam block by mixing carbon dioxide with a (substantially dry) foam precursor mixture having a matrix-forming material and a biomaterial, stagewise experiments were conducted as follows.Materials

[0063] The following materials were used:Table 1Stagewise Processing

[0064] Foam precursor composition was prepared by mixing polyvinyl pyrrolidone with oxidized regenerated cellulose and collagen along with other additives. Polyvinyl pyrrolidone was mixed with glycerol, benzalkonium chloride, 1,2-octanediol and citrate buffer, in an amount as shown in Table 2 below.Table 2

[0065] To this mixture (mixture-1), the biomaterial (i.e. Promogran™ Matrix) having 45% (w / w) oxidized regenerated cellulose and 55% (w / w) of bovine collagen, was added in an amount as shown in Table 3 to obtain the foam precursor mixture.Table 3

[0066] The foam precursor mixture was kneaded in a Barbender kneader at a temperature of 23 °C for a time period of 6 minutes to simulate dynamic mixing. The kneading speed was maintained at a rpm in a range of 40 to 150. The mixture was then placed in an oven at a temperature of 80°C for about30 mins. The mixture was further mixed briefly to simulate the formation of the compounded foam precursor composition.

[0067] The compounded foam precursor mixture was then placed in high pressure reactor with heating jacket and mixed with supercritical carbon dioxide at a temperature of 80°C and pressure of 120 bar to simulate the static mixing stage. This resulted in the formation of the foam block with a solid content of about 20-25% by volume. The foam block appeared uniform indicating a relatively small and uniform air bubble size and distribution.

[0068] Thus, it was observed that the formation of foam blocks was possible using carbon dioxide and a substantially dry foam precursor mixture instead of the conventional freeze-drying technique. Since such a process of formation of foam blocks lends itself easily to the continuous manufacture of foam dressing as described in the present disclosure, it is expected to substantially reduce manufacturing time and cost and provide flexibility in the selection of the raw materials that can be used for manufacturing the foam dressing.

Claims

CLAIMSWhat is claimed is:

1. A method comprising: compounding a foam precursor mixture, the foam precursor mixture comprising a matrixforming material and a biomaterial; mixing supercritical carbon dioxide with the foam precursor mixture to form a foam block; passing the foam block through an extrusion die to form a foam slab; and calendering the foam slab to obtain a foam dressing.

2. The method of claim 1, wherein the calendering comprises laminating upper and lower surfaces of the foam slab with upper and lower liner films.

3. The method of claim 2 comprising sealing edges of the upper and lower liner films.

4. The method of claim 1, wherein the matrix-forming material comprises at least one of polyvinylpyrrolidone (PVP), lipids, polyvinylacetate (PVA), and polyethylene glycol.

5. The method of claim 1, wherein the biomaterial comprises at least one of collagen (type I, II, III), alginate, oxidized regenerated cellulose (ORC), and hyaluron.

6. The method of claim 1, wherein the foam precursor mixture comprises 60% to 99% by weight of the matrix-forming material and 1% to 25% by weight of the biomaterial.

7. The method of claim 6, wherein the foam precursor mixture further comprises 0.01% to 5% by weight of an antimicrobial material.

8. The method of claim 7, wherein the antimicrobial material comprises one or more of benzalkonium chloride (BAC), tetracycline, penicillins, terramycins, erythromycin, bacitracin, neomycin, polymycin B, mupirocin, clindamycin, colloidal silver, silver salts, silver sulfadiazine, chlorhexidine, povidone iodine, triclosan, sucralfate, quaternary ammonium salts, potassium chloride (KCI), Chitosan, Chlorhexidine gluconate, and metals selected from silver, copper, or zinc.

9. The method of claim 6, wherein the foam precursor mixture further comprises 1% to 30% by weight of an additive.

10. The method of claim 9, wherein the additive comprises one or more of pH adjusting agents, buffers, a mono-ol, and a polyol.

11. An apparatus comprising: a dynamic mixer to compound a foam precursor mixture, the foam precursor mixture comprising a matrix-forming material and a biomaterial; a fluid reservoir to store, at a predetermined pressure and temperature, liquefied carbon dioxide and supply carbon dioxide for mixing with the foam precursor mixture; a static mixer in fluid communication with the outlet of the dynamic mixer, wherein the static mixer is to mix the foam precursor mixture received from the dynamic mixer and the carbon dioxide to form a foam block;an extrusion die in fluid communication with an outlet of the static mixer to form a foam slab from the foam block; and a rolling unit in fluid communication with an outlet of the extrusion die for calendering the foam slab to obtain a foam dressing.

12. The apparatus of claim 11, wherein the dynamic mixer is one of a single-screw coextruder and a multi-screw coextruder.

13. The apparatus of claim 11 , further comprising a drying unit to predry the foam precursor mixture to substantially remove moisture therefrom before the foam precursor mixture is supplied to the dynamic mixer.

14. The apparatus of claim 11, further comprising liner supply units to supply upper and lower liner films to the rolling unit to laminate upper and lower surfaces of the foam slab during calendering.

15. The apparatus of claim 14 comprising a sealing unit to seal edges of the upper and lower liner films upon lamination.

16. A foam dressing manufactured by the method of claim 1.

17. The foam dressing of claim 16, wherein the foam dressing has a solid content of 10-30% by volume.

18. A composition of a foam precursor mixture for use in manufacturing a foam dressing, the composition comprising: a matrix-forming material; and a biomaterial, wherein the matrix-forming material and the biomaterial are present in a ratio that allows for the formation of a foam block when subjected to a foam production process with supercritical carbon dioxide.

19. The composition of claim 18, wherein the matrix-forming material is present in an amount of 60% to 99% by weight and the biomaterial is present in an amount of 1% to 25% by weight.

20. The composition of claim 18, further comprising an antimicrobial material in an amount of 0.01% to 5% by weight.

21. The composition of claim 18, wherein the matrix-forming material is selected from the group consisting of polyvinylpyrrolidone (PVP), lipids, polyvinylacetate (PVA), and polyethylene glycol, and the biomaterial comprises at least one of collagen (type I, II, III), alginate, oxidized regenerated cellulose (ORC), and hyaluron.

22. The composition of claim 21 , wherein the collagen is selected from the group consisting of bovine collagen, porcine collagen, human collagen, equine collagen, fish collagen, recombinant collagen, or a combination thereof.

23. The composition of claim 18, further comprising an additive selected from the group consisting of pH adjusting agents, buffers, mono-ol, or polyol, in an amount of 1% to 30% by weight.

24. A method for preparing a foam precursor mixture for use in manufacturing a foam dressing, the method comprising: providing a matrix-forming material; providing a biomaterial; mixing the matrix-forming material and the bio material to form an initial mixture; and drying the initial mixture to substantially remove moisture therefrom, thereby obtaining the foam precursor mixture.

25. The method of claim 24, wherein the matrix-forming material is added in an amount of 60% to 99% by weight of the foam precursor mixture and the biomaterial is added in an amount of 1% to 25% by weight of the foam precursor mixture.

26. The method of claim 24, further comprising adding an antimicrobial material to at least one of the matrix-forming material, the biomaterial, and the initial mixture.

27. The method of claim 26, wherein the antimicrobial material is added in an amount of 0.01% to 5% by weight of the foam precursor mixture.

28. The method of claim 27, wherein the drying step is performed at a temperature and for a duration sufficient to reduce the moisture content to a predetermined level suitable for subsequent foam formation.

29. The method of claim 24, further comprising adding at least one additive selected from the group consisting of pH adjusting agents, buffers, mono-ol, or polyol, to at least one of the matrix-forming material, the biomaterial, and the initial mixture.

30. The method of claim 29, wherein the additive is added in an amount of 1% to 30% by weight of the foam precursor mixture.

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