Method of making wound dressings

Abstract

A method. The method includes making a wound dressing, the method comprising: mixing dry collagen, oxidized regenerated cellulose (ORC) and melt bonding fibers to form a mixture; and heating the mixture.

Description

[0001] METHOD OF MAKING WOUND DRESSINGS

[0002] BACKGROUND

[0003] Collagen dressings are used as wound care products. These products are primarily derived from bovine collagen sources, particularly bovine skin, and processed via acid or enzymatic extraction methods into purified and largely type I collagen material. Collagen dressings can improve collagen and fibroblast activity at a wound site. There is a need to provide better collagen dressings in a form useful for treating wounds.

[0004] SUMMARY

[0005] Thus, in one aspect, the present disclosure provides a method of making a wound dressing, the method comprising: mixing dry collagen, oxidized regenerated cellulose (ORC) and melt bonding fibers to form a mixture; and heating the mixture.

[0006] Various aspects and advantages of exemplary embodiments of the present disclosure have been summarized. The above Summary is not intended to describe each illustrated embodiment or every implementation of the present disclosure. Further features and advantages are disclosed in the embodiments that follow. The Drawings and the Detailed Description that follow more particularly exemplify certain embodiments using the principles disclosed herein.

[0007] BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1 is SEM image of Nonwoven web of Example 1 (60x magnification).

[0009] FIG. 2 is SEM image of Non woven web of Example 1 (220x magnification).

[0010] FIG. 3 is SEM image of Nonwoven web of Example 2 (80x magnification).

[0011] FIG. 4 is SEM image of Nonwoven web of Example 2 (170x magnification).

[0012] DETAILED DESCRIPTION

[0013] Before any embodiments of the present disclosure are explained in detail, it is understood that the invention is not limited in its application to the details of use, construction, and the arrangement of components set forth in the following description. The invention is capable of other embodiments and of being practiced or of being carried out in various ways that will become apparent to a person of ordinary skill in the art upon reading the present disclosure. Also, it is understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. It is understood that other embodiments may be utilized and structural or logical changes may be made without departing from the scope of the present disclosure.

[0014] As used in this Specification, the recitation of numerical ranges by endpoints includes all numbers subsumed within that range (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.8, 4, and 5, and the like).

[0015] Unless otherwise indicated, all numbers expressing quantities or ingredients, measurement of properties and so forth used in the Specification and embodiments are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and attached listing of embodiments can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings of the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claimed embodiments, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0016] The method by which most collagen dressings are manufactured are using freeze drying or lyophilization processes which remove the water content in cast collagen solutions to leave a porous matrix of protein and other components. This manufacturing process is time consuming and involves a batch process as opposed to continuous.

[0017] The methods of the present disclosure addresses this challenge by teaching a nonwovens- based processing starting with dry materials as opposed to protein solutions in mild acid and are useful as providing wound dressings and in the healing of wounds (both acute and chronic). This process can provide a semi-continuous or continuous method of making collagen dressings with preferential compositions.

[0018] In some embodiments, an method of making a wound dressing is described. The method can include mixing dry collagen, oxidized regenerated cellulose (ORC) and melt bonding fibers to form a mixture and heating the mixture. The method can further include compressing the mixture to form the wound dressing, for example, with a weight or with a roller. In some embodiments, the mixture can be heated at a process temperature of melt bonding fibers, for example, 250 to 280 F degree. In some embodiments, the method does not include adding an acid to the mixture.

[0019] In some embodiments, the dry collagen and oxidized regenerated cellulose can be in a form of particles In some embodiments, the dry collagen and oxidized regenerated cellulose are mixed in a weight ratio of 60:40 to 40:60 or 55:45 to 45:55 collagemORC. In some embodiments, the dry collagen and oxidized regenerated cellulose are mixed in a weight ratio of about 60:40, 55:45, 50:50, 45:55 or 40:60 collagemORC. In some embodiments, the wound dressing can inlcude 5 to 25 wt%, 10 to 20 wt%, 12 to 18 wt%, or 13 to 17 wt%, melt bonding fibers based on the total weight of the wound dressing. In some embodiments, the wound dressing can inlcude more than 5wt%, 10 wt%, 12 wt%, 13 wt%, 15 wt% or 20% melt bonding fibers based on the total weight of the wound dressing. In some embodiments, the wound dressing can inlcude less than 25 wt%, 20 wt%, 19 wt%, 18 wt%, 17 wt%, 15 wt% or 10 wt% melt bonding fibers based on the total weight of the wound dressing.

[0020] Any suitable sources of collagen can be used. For example, the species from which the collagen is obtained could be human, bovine, porcine, or other animal sources. Collagen can also be obtained from recombinant sources. In some embodiments, the dry collagen is substantially free of an acid, for emaple, acetic acid or hydrochloric acid. In some embodiments, the dry collagen is free of an acid.

[0021] The melt bonding fibers can be polymeric fibers. Melt bonding fibers are typically formed by extruding the molten thermoplastic material through a plurality of fine, usually circular, die capillaries as molten threads or filaments into high velocity, usually heated gas (e.q. air) stream which attenuates the filaments of molten thermoplastic material to reduce their diameter. Thereafter, the melt bonding fibers are carried by the high velocity gas stream and are deposited on a collecting surface to form a web of randomly distributed melt bonding fibers.

[0022] Thermoplastic material can include polyurethane elastomer, polybutylene elastomer, polyester elastomer, a hydrogenated styrene isoprene / butadiene styrene block copolymer(s). Suitable polyolefins for making the nonwoven web include, but are not limited to, polyethylene, polypropylene, polyethylene terephthalate, poly(l -butene), copolymers of ethylene and propylene, alpha olefin copolymers (such as copolymers of ethylene or propylene with 1 -butene, 1 -hexene, 1- octene, and 1-decene), poly(ethylene-co-l -butene), poly(l -methylpentene) and poly(ethylene-co-l- butene-co- 1 -hexene) .

[0023] Further details on the manufacturing method of melt bonding fibers of this invention may be found in Wente, Superfine Thermoplastic Fibers, 48 INDUS. ENG. CHEM. 1342(1956), or in Wente et al.. Manufacture of Superfine Organic Fibers, (Naval Research Laboratories Reort No. 4364, 1954).

[0024] In some embodiments, the wound dressing can be a composite dressing having a nonwoven structure. The composite dressing is a dressing having more than one component, material, or layer. The nonwoven structure can be a nonwoven fibrous web of polymeric fibers. As used herein, the term “nonwoven fibrous web” refers to a fabric that has a structure of individual fibers or filaments which are randomly and / or unidirectionally interlaid in a mat-like fashion. In some embodiments, at least some of the collagen and ORC are attached to the melt bonding fibers by melt bonding. Heating the mixture to process tempareture of the melt bonding fibers followed by cooling can result in the formation of fiber bonding regions where individual fibers in the web cross over and are in contact with each other - where the cooling of the heated mixture results in fixing of the fiber bonding regions. Collagen and ORC in the mixture can also become physically attached to the fibers by the fiber melting and cooling process. And one advantage of the method is that the bonding of fibers at contact points can provide stability to the non wo ven web.

[0025] In some embodiments, the wound dressing can include a carrier. In some embodiments, the carrier can be a release liner. The release liner carrier may be disposed on the opposing major surface of both major surfaces such that the collagen containing sheet is between the release liner layers.

[0026] Various release liners are known such as those made of (e.g. kraft) papers, polyolefin films such as polyethylene and polypropylene, or polyester. The films are preferably coated with release agents such as fluorochemicals or silicones. For example, U.S. Pat. No. 4,472,480 describes low surface energy perfluorochemical liners. Examples of commercially available silicone coated release papers are POLYSLIK™, silicone release papers available from Rexam Release (Bedford Park, Ill.) and silicone release papers supplied by LOPAREX (Willowbrook, Ill.). Other nonlimiting examples of such release liners commercially available include siliconized polyethylene terephthalate films commercially available from H. P. Smith Co. and fluoropolymer coated polyester films commercially available from 3M under the brand "ScotchPak™" release liners.

[0027] In other embodiments, the carrier may comprise a variety of other (e.g. flexible and / or conformable) carrier materials such as polymeric films and foams as well as various nonwoven and woven fibrous materials, such as gauze. In some embodiments, the carrier is absorbent, such as an absorbent foam. In other embodiments, the carrier layer is non-absorbent, such as a polymeric film.

[0028] Basis weights of the wound dressing made by the present method are much higher than most collagen dressings manufactured using freeze drying or lyophilization processes. In some embodiments, 25 cm2wound dressing made by the present method has a basis weight of 30 to 300 GSM, 50 to 300 GSM, 100 to 300 GSM or 200 to 300 GSM.

[0029] The following working examples are intended to be illustrative of the present disclosure and not limiting.

[0030] EXAMPLES

[0031] Materials

[0032] Collagen powder (<4 mm particle size) was obtained from Collagen Solutions, Eden Prairie, MN. Oxidized Regenerated Cellulose (ORC) powder (<500 micron particle size) was obtained from Ethicon, Inc., Raritan, NJ.

[0033] Dulbecco’s Modified Eagle Medium (DMEM) was obtained as GIBCO brand product #11995065 from Thermo Fisher Scientific, Waltham, MA.

[0034] Penicillin-Streptomycin-Glutamine solution (100X) was obtained as GIBCO brand product #10378016 from Thermo Fisher Scientific, Waltham, MA.

[0035] Fetal Bovine Serum (FBS) was obtained as GIBCO brand product #16000044 from Thermo Fisher Scientific, Waltham, MA.

[0036] Dulbecco’s Modified Eagle Medium Complete (DMEM-C) was prepared by supplementing the commercial DMEM with 10% FBS (by volume) and 1% of the penicillin-streptomycin-glutamine solution (by volume).

[0037] Human Dermal Fibroblasts, adult (HDFa) were obtained as GIBCO brand product #C0135C from Thermo Fisher Scientific, Waltham, MA.

[0038] CYQUANT MTT Cell Viability Assay Kits (product #V13154) were obtained from Thermo Fisher Scientific, Waltham, MA.

[0039] The melt bonding fibers (MBF) were bicomponent fibers with a polyethylene (PE) sheath and polyethylene terephthalate (PET) core construction (1.3 dex, 6 mm length) obtained from Trevira GmbH, Hattersheim, Germany.

[0040] Methods

[0041] Scanning Electron Microscope (SEM) images of dressings were taken using a JCM-5000 NEOSCOPE Table Top SEM instrument (JEOL USA, Peabody, MA). Images were taken at an accelerating voltage of 10 kV and magnification settings of 60x, 80x, 170x, or 220x magnification.

[0042] Examples

[0043] Example 1.

[0044] Collagen powder (1.8 g), ORC powder (1.8 g), and melt bonding fibers (0.4 g) were combined in a polyethylene jar and mixed by hand shaking of the jar for 10-15 seconds. The mixture was evenly spread in a 10 inch by 10 inch area on a polytetrafluoroethylene carrier mat, heated in an oven at 250 °C for 5 minutes, and then cooled to room temperature. SEM images (FIG. 1 and FIG. 2) of the resulting nonwoven dressing were taken. The images showed a web of melt bonded fibers with patches or clumps of collagen and ORC particles attached to the fibers. The image of FIG.1 was taken at 60x magnification and the image of FIG. 2 was taken at 220x magnification. Example 2.

[0045] Collagen powder (1.8 g), ORC powder (1.8 g), and melt bonding fibers (0.4 g) were combined in a polyethylene jar and mixed by hand shaking of the jar for 10-15 seconds. The mixture was evenly spread in a 10 inch by 10 inch area on a carrier mat. A 514 g weight was placed on top of the mixture to create an assembly that compressed the mixture. The weight (10 inch by 10 inch) was a diamond patterned screen (opening dimensions of 1 inch length by 0.5 inch width). The assembly was placed in an oven and heated at 270 °C for 5 minutes. The assembly was then cooled to room temperature and the weight was removed. SEM images (FIG. 3 and FIG. 4) of the resulting nonwoven dressing were taken. The images showed a web of melt bonded fibers with patches or clumps of collagen and ORC particles attached to the fibers. The image of FIG. 3 was taken at 80x magnification and the image of FIG. 4 was taken at 170x magnification.

[0046] Example 3. Cell Viability Assay

[0047] A single collagen sample selected from either Example 1 or 2 was added at a 10 mg / mE concentration to a vial containing DMEM that was supplemented with the penicillin-streptomycin- glutamine solution (1% by volume). Each sample was completely immersed in the media for 48 hours at 4 °C with gentle agitation and then centrifuged at 300 g for 5 minutes. The resulting supernatant media from each sample was sterile filtered using a 0.22 micron filter.

[0048] Human Dermal fibroblasts (HDFa) were cultured in DMEM-C and seeded into a 24-well tissue treated plate at 10,000 cells per well. Cells were allowed to adhere overnight. Next, the plate was centrifuged at 300 g for 5 minutes. The supernatant DMEM-C media in a well was then removed and replaced with 1 mL of sterile filtered media prepared from either Example 1 or Example 2. A control well was also prepared in which the original DMEM-C was removed and replaced with DMEM that was supplemented with the penicillin-streptomycin-glutamine solution (1% by volume). The cells were cultured for 24 hours and then evaluated for cell viability using a CYQUANT MTT Cell Viability Assay Kit according to the manufacturer’s instructions. The percent cell viability values were determined relative to the cell viability result for the control. There was not a statistically significant difference between the results for the control and Example 1-2 samples based on an analysis of variance (ANOVA) comparison. The results are reported in Table 1.

[0049] Table 1.

[0050] Example 4.

[0051] Five different mixtures of collagen powder, ORC powder, and melt bonding fibers were used to prepare individual dressings. The mixtures varied in the total weight of the component mixture and the weight percent (wt%) of the melt binding fiber (MBF) component. The three components of each mixture were combined in a polyethylene jar and mixed by hand shaking of the jar for 10-15 seconds. Each mixture was then evenly spread in a 6 inch by 6 inch area on a polytetrafluoroethylene carrier mat. The weight described in Example 2 was placed on top of the mixture to create an assembly that compressed the mixture. In the assembly, a thin sheet of polytetrafluoroethylene (6 inch by 6 inch) was placed between the screen and the surface of the mixture. Each assembly was placed in an oven and heated at 270-280 °C for 5 minutes. Each assembly was then cooled to room temperature and the weight was removed. SEM images of all the nonwoven dressings showed webs of melt bonded fibers with patches or clumps of collagen and ORC particles attached to the fibers. In Table 2, the basis weights and sample thicknesses of the nonwoven dressings are reported.

[0052] Table 2.

[0053] All references and publications cited herein are expressly incorporated herein by reference in their entirety into this disclosure. Illustrative embodiments of this invention are discussed and reference has been made to possible variations within the scope of this invention. For example, features depicted in connection with one illustrative embodiment may be used in connection with other embodiments of the invention. These and other variations and modifications in the invention will be apparent to those skilled in the art without departing from the scope of the invention, and it should be understood that this invention is not limited to the illustrative embodiments set forth herein. Accordingly, the invention is to be limited only by the claims provided below and equivalents thereof.

Claims

What is claimed is:

1. A method of making a wound dressing, the method comprising: mixing dry collagen, oxidized regenerated cellulose (ORC) and melt bonding fibers to form a mixture; and heating the mixture.

2. The method of claim 1, further comprising compressing the mixture to form the wound dressing.

3. The method of claims 1-2, wherein the dry collagen and ORC are in a form of particles.

4. The method of claims 1 -3, wherein the dry collagen and ORC are mixed in a weight ratio of 60:40 to 40:60 collagemORC.

5. The method of claims 1 -4, wherein the dry collagen and ORC are mixed in a weight ratio of about 55:45 collagemORC.

6. The method of claims 1-5, wherein the wound dressing comprises 5 to 25 wt% melt bonding fibers based on the total weight of the wound dressing.

7. The method of claims 1-6, wherein 25 cm2wound dressing has a basis weight of 30 to 300 GSM.

8. The method of claims 1-7, wherein the mixture is heated to a process temperature of melt bonding fibers.

9. The method of claim 8, wherein the process temperature is from 250 to 280 F degree.

10. The method of claims 1-9, wherein the dry collagen is substantially free of an acid.

11. The method of claims 1-10, wherein the wound dressing is a composite dressing having a nonwoven structure.

12. The method of claims 1-11, wherin at least some of the collagen and ORC are attached to the melt bonding fibers by melt bonding.

13. The method of claims 1-12, wherein the method does not include adding an acid to the mixture.

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