TWI754279B - Wound healing kit for producing artificial scabs - Google Patents

Abstract

The present invention relates to a wound healing kit for producing artificial scabs, including a bacterial cellulose membrane and collagen gel. The invention also relates to a patch for producing artificial scabs and use of bacterial cellulose membranes and collagen gel in the manufacture of artificial scabs for wound healing.

Description

Wound repair kit for creating artificial crusts

The present invention relates to a wound repair kit for producing artificial crust, in particular to a wound repair kit comprising biological fiber membrane and collagen gel.

The types of wounds can be roughly divided into: acute bleeding wounds, chronic inflamed wounds, and deep wounds that are difficult to heal. In many wounds, the amount of bleeding is not enough to produce a scab, and the lack of scab provides an external barrier coverage, resulting in direct exposure of the wound to the outside. In the environment, bacteria and viruses stick to the infection and become inflamed. As a result, the wound is slow to heal and prone to scar tissue, which may further lead to serious infection and amputation.

Pressure injuries in chronically inflamed wounds, often in areas that have been under pressure for a long time, such as pressure ulcers in the buttocks of bedridden patients or abdominal pressure ulcers in quadrupeds on their stomach for extended periods of time. Such external wounds cannot form a protective outer layer of crusts, resulting in slow recovery of the wounds, and even repeated inflammations that expand the scope of damage. Therefore, if artificial crusts can be produced with appropriate biomaterials to cover wounds and simulate a cellular microenvironment close to natural wound recovery, in order to reduce the frequency of dressing changes, isolate external sources of infection, and reduce scar tissue, it will be beneficial to humans. and animal wound care to provide effective help.

In one aspect, the present invention relates to a wound repair kit for producing artificial crusts.

In another aspect, the present invention relates to a patch for creating an artificial crust.

In yet another aspect, the present invention relates to the use of a biological fiber membrane and collagen gel in the preparation of artificial crusts for treating wounds.

The present invention is exemplified by the following examples, but the present invention is not limited by the following examples.

The present invention provides a wound repair kit for producing artificial crust, comprising a biological fiber membrane and a collagen gel, wherein the collagen gel contains about 50-250 µg/mL collagen, about 150-250 mg /mL gel, and about 0~50 µg/mL antimicrobial agent.

The present invention also provides a patch for producing artificial crust, comprising a biofiber membrane, the biofiber membrane has a first surface and a second surface, the first surface has a collagen gel layer, the collagen The gel layer is used for contacting with a user, so that the biofiber membrane is attached to the user.

The invention also provides the use of a biological fiber membrane and collagen gel in preparing artificial crusts for treating wounds.

In certain embodiments, the collagen gel comprises about 50-250 μg/mL collagen, about 150-250 mg/mL gel, and about 0-50 μg/mL antibacterial agent.

In certain embodiments, the concentration of the collagen is about 50-250 μg/mL, preferably including but not limited to about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, about 150, about 160, about 170, about 180, about 190, about 200, about 210, about 220, about 230, about 240, about 250 µg/mL, or 50~250 µg Any concentration/mL, not limited to an integer concentration, such as, but not limited to, 168.56 µg/mL, 203.7 µg/mL, etc.; in certain embodiments, the concentration of collagen is about 100 µg/mL.

In some specific embodiments, the concentration of the gel is about 150-250 mg/mL, preferably including but not limited to about 150, about 160, about 170, about 180, about 190, about 200, about 210, about 220, about 230, about 240, about 250 mg/mL, or any concentration from 150 to 250 mg/mL, not limited to an integer concentration, such as, but not limited to, 196.47 mg/mL, 226.87 mg/mL, etc.; In certain embodiments, the concentration of the gel is about 180-200 mg/mL.

In certain specific embodiments, the concentration of the antibacterial agent is about 0-50 μg/mL, preferably including but not limited to about 1, about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50 µg/mL, or any concentration of 0~50 µg/mL, not limited to an integer concentration, such as, but not limited to, 0.01, 3.47, 28.94 µg/mL, etc.; In some embodiments, the concentration of the antibacterial agent is about 30 μg/mL.

The wound repair kit of the present invention can be used for various types of wounds, such as large-area burns, pressure ulcers (ie, pressure wounds, also known as bedsores), wounds of diabetic patients, and wounds of various depths. In addition, the wound repair kit of the present invention can be used for humans, domestic animals, pets, and even wild animals of different sizes. When used in animals, because the wound repair kit of the present invention can promote wound repair and the frequency of dressing change is low, it can reduce the cost and inconvenience of animal management such as immobilization or anesthesia due to discomfort of dressing change.

The wound repair kit of the present invention is easy to operate. It is recommended to pre-treat the wound before use, scrape the hair around the wound according to the needs of the wound, clean the wound with physiological saline, and wipe the skin around the wound with a disinfectant such as iodine solution. After finishing the wound pretreatment, cut the required area of the biofiber membrane according to the size of the wound, preferably 1-2 cm larger than the edge of the wound area to ensure that the biofiber membrane can cover the entire wound; if the wound area is larger than the area of a single biofiber membrane , you can use multiple biofiber membranes with their borders overlapping by 1-2 cm; apply collagen gel to the cut biofiber membrane in a similar way to glue, and then completely attach it to the wound to be treated above, the operation of the wound repair kit of the present invention is completed. The artificial scab formed by using the present invention usually does not need to be replaced, that is, does not need to change the dressing. After the underlying skin is healed, the artificial scab will fall off in a manner similar to the fragmentation of the natural scab. If the wound is infected after use due to incomplete wound debridement, after re-debridement, the wound repair kit of the present invention can be used with the above steps to form artificial crusts again.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to "a component" includes a plurality of such components and their equivalents known to those skilled in the art.

As used herein, "about", "about" or "approximately" generally means within 20%, preferably within 10%, more preferably within 5% of a given value or range. Amounts given herein are approximations and their representations can be inferred to refer to the terms "about," "about," or "approximately," unless expressly stated otherwise.

。 生物纖維的直徑約為20~100 nm。可產生生物纖維的細菌菌屬包含，但不限於，醋桿菌(Acetobacter )、固氮菌(Azotobacter )、醋酸菌(Komagateibacter )、根瘤菌(Rhizobium )、假單胞菌(Pseudomonas )、沙門氏菌(Salmonella )、產鹼菌(Alcaligenes )，以及八疊球菌(Sarcina )；實例包含，但不限於，木醋桿菌(Acetobacter xylinum )、漢氏醋桿菌(Acetobacter hansenii )、巴氏醋桿菌(Acetobacter pasteurianus )、漢氏糖桿菌(Gluconacetobacter hansenii )、木糖葡糖桿菌(Gluconacetobacter xylinus )、木質醋酸菌(Komagataeibacter xylinus )。As used herein, the term "biocellulose", also known as "bacterial cellulose" refers to an organic compound having the formula (C ₆ H ₁₀ O ₅ ) _n produced by bacteria, which is a linear polymerization of D-glucose It is connected by β-(1,4) glycosidic bond and has the following molecular structure:

. The diameter of biofibers is about 20–100 nm. The genera of bacteria that can produce biofibers include, but are not limited to, Acetobacter , Azotobacter , Komagateibacter , Rhizobium , Pseudomonas , Salmonella , Alcaligenes , and Sarcina ; examples include, but are not limited to, Acetobacter xylinum , Acetobacter hansenii , Acetobacter pasteurianus , Gluconacetobacter hansenii , Gluconacetobacter xylinus , Komagataeibacter xylinus .

As used herein, the term "biofiber membrane" refers to a film with a nonwoven structure made from biofiber (also known as bacterial cellulose) as a raw material. The pores of the biofibrous membrane are extremely small, allowing the passage of air and water molecules, maintaining the humidity required by the wound, but at the same time blocking the penetration of all microorganisms, including bacteria and viruses. The biofiber membrane used in the present invention has a pH of about 7.0 +/- 1.0, a moisture content of about 4% to 20% (w/w), a thickness of about 5 to 25 µm, and a basis weight of about 10 to 30 g. /m ² , sterilized by high temperature and high pressure or γ-ray, and without pyrogen. Biofibrous membranes useful in the present invention are commercially available, such as, but not limited to, DermaFill® (Cellulose Solutions LLC, Alabama, USA).

As used herein, the term "collagen gel" refers to a gel formulation containing collagen. The collagen gel of the present invention may further comprise an antibacterial agent. The collagen gel of the present invention can be used as an adhesive of the biological fiber membrane, so that the biological fiber membrane can be adhered to the wound surface to be treated. In addition, the collagen in the collagen gel can accelerate wound recovery, and if it contains an antibacterial agent, the antibacterial effect can be achieved.

As used herein, the term "collagen" refers to the main structural protein of the extracellular matrix in various connective tissues in animals. Its molecular structure is a triple helix and consists of three polypeptides entangled with each other. Sources of collagen include, but are not limited to, terrestrial animals (eg, chickens, ducks, geese, pigs, cattle, sheep, donkeys, horses, etc.) and aquatic animals (eg, fish, echinoderms, cephalopods, shellfish, etc.). In a specific embodiment, the collagen gel of the present invention uses fish collagen with a molecular weight ranging from, but not limited to, about 100 kDa to about 220 kDa.

As used herein, the term "gel" refers to a non-flowing colloidal network copolymer or a continuous network copolymer that is swelled by a fluid throughout its entire volume. Gels are semi-solid and have no fluidity at steady state. Gels useful in the present invention comprise various types of copolymers such as, but not limited to, high molecular weight hydrogels [eg, block copolymers Poloxamer 407, Poloxamer 181 , Pluronics L61; Poly(acrylic acid), polymethylacrylic acid, Polyacrylamide], Polypeptide gel [eg, poly-L-lysine acid (poly-L-lysine), poly(L-glutamic acid), collagen], polysaccharide gels (eg, cellulose, starch, hyaluronic acid, alginic acid, several Butylan). In some specific embodiments, block copolymer poloxamer 407 is used as the gel material. Poloxamer is a non-ionic triblock copolymer composed of polyoxypropylene linking two sections of hydrophilic polyoxyethylene. It has an amphiphilic molecular structure, which increases the water solubility of hydrophobic oily substances or increases the miscibility of different hydrophobic substances. . In these embodiments, poloxamer 407 forms a collagen gel after binding to collagen.

As used herein, the term "antimicrobial" refers to an agent that kills microorganisms or prevents their growth. The types of antibacterial agents that can be used in the collagen gel of the present invention include, but are not limited to, metal ion antibacterial agents, metal nanoparticle antibacterial agents, natural essential oil antibacterial agents, and polyamine antibacterial agents. In certain embodiments, nano-silver is added as an antibacterial agent to the collagen gel of the present invention.

As used herein, the term "artificial crust" refers to the crust structure formed by the biofibrous membrane and collagen gel contained in the kit of the present invention, plus proteins in the exudate of the subject's own wound tissue. The bio-fibrous membrane of the present invention has extremely high biocompatibility, and is attached to the wound surface as an outer layer to isolate microorganisms, and the collagen gel between the bio-fibrous membrane and the wound can not only make the bio-fibrous membrane adhere to the wound surface In addition, it will also interact with the protein in the wound tissue exudate. After the water evaporates, the biofibrous membrane, the collagen gel, and the protein in the wound tissue exudate will accumulate and harden, forming a crust-like crust. Layered, this is the artificial crust structure. The artificial crust structure of the present invention covers the wound, provides a microenvironment that can promote wound repair, accelerates wound healing, and reduces the frequency of dressing changes.

The present invention is described in more detail in the following illustrative examples. While the embodiments may represent only selected specific embodiments of the invention, it is to be understood that the following embodiments are illustrative and not restrictive.

Example

Example 1 Human upper arm medial burn and scald repair test

Test material: The wound repair kit of the present invention includes a biofiber membrane (pH value is about 7.0 +/- 1.0, moisture content is about 4%~20% (w/w), thickness is about 5~25 µm, base Weighing about 10~30 g/m ² , sterilized by high temperature and high pressure or γ-ray, and without pyrogen), and collagen gel (containing 100 µg/mL perch eel skin collagen, 180~200 mg/mL polo Sharm 407, 30 µg/mL nanosilver in sterile water).

Test subject: A human subject (Mongolian race, male, 39 years old) caused two burns and scalds on the inner side of his left upper arm with a laser for medical cosmetology. The laser wavelength of each wound is 1064 nm, the laser dose is 3.2 J/cm ² , the laser area is 19.8*19.8 mm ² , and the coverage rate is 88%.

Test method: After the above laser treatment, a wound was randomly selected as the control group, and only disinfection treatment was carried out. The test group, after carrying out the same disinfection treatment as the control group, used the wound repair set of the present invention for 25 days, and the method was as follows: cut the required biofiber membrane to make its area larger than the edge of the wound area by 1-2 cm to ensure The entire wound can be covered; after the collagen gel is applied to either side of the biofiber membrane (the side that will be in contact with the wound) in a manner similar to applying glue, the The surface was attached to the wound of the experimental group for 25 days, during which the biofiber membrane was not replaced. Follow-up observations were made and photographed.

Results: As shown in Figures 1A to 1F. The wounds in the experimental group formed an artificial crust structure on the 2nd day after the occurrence of burns, while the wounds in the control group slowly formed a natural crust structure from autologous tissue (as shown in Figure 1A). On the 8th day, it was observed that the artificial scab on the wound of the experimental group gradually and uniformly thickened, while the wound of the control group formed a natural and uneven scab structure from autologous tissue. The crust in the center is thinner (as shown in Figure 1B). On the 12th day, it was observed that the artificial scab on the wound of the experimental group was obviously hardened but the structure was still intact, while the natural scab formed by the autologous tissue of the wound of the control group was still uneven (as shown in Figure 1C). On the 25th day, the wound of the test group had healed until the artificial crust completely fell off, while the natural crust structure formed by the autologous tissue in the wound of the control group was fragmented and partially fell off, causing the wound to be exposed to the outside again and even infected and bleeding (such as shown in Figure 1D). On the 53rd day, both the wounds of the experimental group and the control group had recovered, but the wounds of the control group had obvious scar tissue, while the wounds of the experimental group had no such scar tissue (as shown in FIG. 1E ). After 3 years of follow-up, it can be observed that there is only partial pigment deposition in the wounds of the experimental group but the skin of the wounds is flat, while the wounds of the control group have obvious scar tissue formation with prominent granulation-like structures (as shown in Figure 1F).

It can be seen that the wound repair kit of the present invention is easy to operate, does not require frequent dressing changes, can accelerate the formation of crusted structures on human skin, shorten the wound healing time, and the wound scars after healing are not obvious.

Embodiment 2 A trial of abdominal pressure ulcer repair in Taiwanese macaques

Test material: Same as Example 1.

Test object: The animal case of this example is the primate Taiwanese macaque ( Macaca cyclopsis , male, estimated age about 25 years old) housed in the Conservation Wildlife Shelter Center (Pingtung, Taiwan). Poor posture and pressure on the abdomen cause large pressure ulcers. Clinical blood tests showed significant inflammation and mild anemia in this case. The clinical symptoms of this case included diarrhea and a large area of abdominal wound was obviously red and swollen.

Test method: First, the pressure sore site of the case was cleaned with normal saline, and the skin around the pressure sore was wiped with a disinfectant such as iodine solution; then, since the area of the abdominal pressure sore in this case was larger than that of a single biofiber membrane, multiple sheets were used. The biofiber membrane is used with the border overlapping by 1-2 cm to ensure that the entire pressure ulcer can be covered; the collagen gel is applied to the inner surface of the multiple biofiber membranes in a similar way to glue (will be in contact with the pressure ulcer wound). After that, the inner surfaces of the plurality of biofibrous membranes coated with collagen gel were attached to the abdominal pressure ulcer wound of this case in a way that the border overlapped by 1-2 cm for a total of 23 days. Serious, so every 3 to 4 days to replace the wound repair set of the present invention. Follow-up observations were made every 3 to 4 days, and photographs were taken to record.

Results: As shown in Figure 2A to Figure 2D. The abdominal pressure ulcer in this case was obviously red and swollen before treatment (as shown in Figure 2A), and the redness and swelling subsided significantly on the 3rd day after using the wound repair set of the present invention (as shown in Figure 2B). The size of the sore was reduced, the redness and swelling of the wound had been greatly improved (as shown in Figure 2C), and by day 23, the pressure ulcer had completely healed (as shown in Figure 2D).

It can be seen that the wound repair set of the present invention is convenient to operate, does not require frequent dressing changes, and can promote the repair of pressure ulcers until they are healed.

Embodiment 3 Tail trauma repair experiment in wild Taiwan macaques

Test material: Same as Example 1.

Test object: The animal case in this example is a primate Taiwanese macaque (male, age unknown) housed in a conservation wild animal shelter (Pingtung, Taiwan), with severe tail trauma and infection due to monkey group fights or other unexpected factors ulcer.

Test method: First, the tail wound of this case was cleaned with physiological saline, and the skin around the wound was wiped with disinfectant such as iodine solution; then, collagen gel was applied to the inner surface of the biofiber membrane in a similar way to glue. After the tail wound contact side), the inner surface of the biofiber membrane coated with collagen gel was attached to the tail wound of the case, and the outer layer of the biofiber membrane was covered with gauze to prevent the case The biofibrous membrane is sloughed off due to activity. Since the wound was seriously infected, the wound repair set of the present invention was replaced every 4 days, and the follow-up observation and photographing were performed.

Results: As shown in Figure 3A to Figure 3D. In this case, the tail wound was severely infected and had ulcers before treatment (as shown in Figure 3A), the tissue growth recovered after the 30th day of using the wound repair kit of the present invention (as shown in Figure 3B), until the 50th day At 75 days, the wound exudate in the tail had been significantly reduced (as shown in Figure 3C), and the skin surface had been completely repaired at 75 days (as shown in Figure 3D).

It can be seen that the wound repair kit of the present invention is easy to operate, and even if it is used on severely infected wounds, daily dressing changes are not required, the frequency of dressing changes can be reduced, and the repair of severely infected wounds can be promoted.

The above detailed description is a specific description of a feasible embodiment of the present invention, but this embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not depart from the technical spirit of the present invention shall be included in the within the scope of the patent in this case.

To sum up, the technical features disclosed in this case have fully met the requirements of the statutory invention patent for novelty and progress, and an application is filed in accordance with the law.

Figure 1 shows the results of the human skin burn and scald repair test. Figures 1A to 1F show the recovery of the skin on day 2, day 8, day 12, day 25, day 53, and 3 years after treatment, respectively. Con. represents the control group; Exp. represents the experimental group.

Figure 2 shows the results of the abdominal pressure ulcer repair test in Taiwanese macaques. Figure 2A shows the redness and swelling of the pressure ulcer before treatment, the left photo is a frontal photo, and the right photo is a side photo; Figure 2B to Figure 2D show the pressure ulcer on the 3rd, 12th, and 23rd days after treatment, respectively The restoration situation, the left photo is a frontal photo, and the right photo is a side photo.

Figure 3 shows the results of the wound repair test on the tail of wild Taiwanese macaques. Figure 3A shows the condition of infected ulcers on the tail before treatment; Figures 3B to 3D show the recovery of the tail skin on the 30th day, the 50th day, and the 75th day after the treatment, respectively.

Claims (8)

A wound repair kit for producing artificial crusts, comprising a biological fiber membrane, and a collagen gel, the collagen gel comprising 50-250 μg/mL collagen, 150-250 mg/mL gel, and 0 ~50 μg/mL antimicrobial. A patch for producing artificial crusts, comprising a biological fibrous membrane, the biological fibrous membrane has a first surface and a second surface, the first surface has a collagen gel layer, the collagen gel layer is It is used for contacting with a user, so that the biofiber membrane is attached to the user. The patch of claim 2, wherein the collagen gel comprises 50-250 μg/mL collagen, 150-250 mg/mL gel, and 0-50 μg/mL antibacterial agent. The invention relates to the use of a double-layer structure of a biological fiber membrane and a collagen gel in preparing an artificial crust for treating wounds. The use according to claim 4, wherein the collagen gel comprises 50-250 μg/mL collagen, 150-250 mg/mL gel, and 0-50 μg/mL antibacterial agent. The wound repair kit according to claim 1, wherein the collagen gel is composed of 50-250 μg/mL collagen, 150-250 mg/mL poloxamer 407, 0-50 μg/mL antibacterial agent and water . The patch of claim 3, wherein the collagen gel is composed of 50-250 μg/mL collagen, 150-250 mg/mL poloxamer 407, 0-50 μg/mL antibacterial agent and water. The use according to claim 5, wherein the collagen gel is composed of 50-250 μg/mL collagen, 150-250 mg/mL poloxamer 407, 0-50 μg/mL antibacterial agent and water.

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