TW202142276A - 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 producing artificial scab

The present invention relates to a wound repair kit for producing artificial scabs, in particular a wound repair kit containing bio-fiber membrane and collagen gel.

The types of wounds can be roughly divided into: acute bleeding wounds, chronic inflammatory wounds, and deep wounds that are difficult to heal. Among them, many wounds with insufficient bleeding to produce scabs, lack of scabs to provide external barrier coverage, resulting in direct exposure of the wound to the outside. In the environment, infections caused by bacteria and viruses become inflamed. As a result, wounds recover slowly and scar tissue is easily produced, which may further lead to serious infections and amputations.

Compression injuries in chronic inflamed wounds are common in areas that have been under pressure for a long time, such as bedsores on the buttocks of patients who have been bedridden for a long time or abdominal pressure sores when quadrupeds lie on their stomachs for a long time. The external wound of this type of pressure injury cannot form a protective outer layer of crust, resulting in slow recovery of the wound, and even repeated inflammation leading to the expansion of the damaged area. Therefore, if an artificial scab can be produced with appropriate biological materials to cover the wound and simulate the cell microenvironment close to natural wound recovery, so as to reduce the frequency of dressing changes, isolate external sources of infection, and reduce scar tissue, it will be beneficial to humans. And provide effective help for animal wound care.

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

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

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

The present invention is illustrated 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 scabs, which includes a biofiber membrane and a collagen gel. The collagen gel contains about 50-250 µg/mL collagen and about 150-250 mg. /mL gel, and about 0-50 µg/mL antibacterial agent.

The present invention also provides a patch for producing artificial scabs, comprising a biofiber membrane having a first surface and a second surface, the first surface has a collagen gel layer, and the collagen The gel layer is used to contact a user, so that the bio-fiber membrane is attached to the user.

The invention also provides a use of bio-fiber membrane and collagen gel in preparing artificial crust for treating wounds.

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

In some 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 of /mL is not limited to an integer concentration, such as, but not limited to, 168.56 µg/mL, 203.7 µg/mL, etc.; in some specific embodiments, the concentration of collagen is about 100 µg/mL.

In some 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 of 150-250 mg/mL, not limited to an integer concentration, for example, but not limited to 196.47 mg/mL, 226.87 mg/mL, etc.; In some specific embodiments, the concentration of the gel is about 180-200 mg/mL.

In some 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, for example, 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 and scalds, pressure sores (also called pressure sores), diabetic wounds, 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 types and sizes. When used in animals, because the wound repair kit of the present invention can promote wound repair and the frequency of dressing is low, it can reduce the cost and inconvenience of management such as immobilization or anesthesia for animals due to the 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, shave the hair around the wound according to the needs of the wound, clean the wound with saline solution, and wipe the skin around the wound with disinfectant such as iodine solution. After finishing the pre-treatment of the wound, cut the required bio-fiber membrane area according to the size of the wound, preferably 1~2 cm larger than the edge of the wound area to ensure that the bio-fiber membrane can cover the entire wound; if the wound area is larger than the area of a single bio-fiber membrane , You can use a plurality of bio-fiber membranes with the boundary overlapping by 1~2 cm; apply the collagen gel to the cut bio-fiber membrane in a glue-like manner, 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 crust formed by using the present invention usually does not need to be replaced, that is, there is no need to change the dressing. After the lower layer of skin is healed, the artificial crust will fall off in a manner similar to the fragmentation of natural crust. If the wound is infected after use due to incomplete debridement, the wound repair kit of the present invention can be used in the above steps after re-debridement to re-form artificial crust.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs.

As used herein, unless the context clearly dictates otherwise, the singular forms "a", "an", and "the" include plural references. 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% of a given value or range, preferably within 10%, more preferably within 5%. The quantities given in this article are approximate, and unless explicitly stated, they can be inferred to refer to the terms "approximately", "approximately" or "approximately".

。 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 "biological fiber", also known as "bacterial cellulose" refers to _{an organic compound with the chemical 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 biological fiber is about 20-100 nm. Fibers can be produced biologically bacterial species include, but are not limited to, Acetobacter (by Acetobacter), nitrogen-fixing bacteria (Azotobacter), acetic acid bacteria (Komagateibacter), Rhizobium (with Rhizobium), Pseudomonas (of Pseudomonas), Salmonella (Salmonella) , Alcaligenes , and Sarcina ; examples include, but are not limited to, Acetobacter xylinum , Acetobacter hansenii , Acetobacter pasteurianus , and Chinese Gluconacetobacter hansenii , Gluconacetobacter xylinus , Komagataeibacter xylinus .

As used herein, the term "biological fiber membrane" refers to a film with a non-woven structure made of biological fiber (also known as bacterial cellulose) as a raw material. The pores of the bio-fiber membrane are extremely small, allowing air and water molecules to pass through, maintaining the humidity required by the wound, but at the same time blocking the penetration of all microorganisms (including bacteria and viruses). The pH value of the biofiber membrane used in the present invention is about 7.0 +/- 1.0, the water content is about 4%-20% (w/w), the thickness is about 5-25 µm, and the basis weight is about 10-30 g /m ² , sterilized by high temperature, high pressure or γ-ray, and no pyrogen. The biofiber membrane that can be used in the present invention is 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 include an antibacterial agent. The collagen gel of the present invention can be used as an adhesive of the biological fiber membrane to make the biological fiber membrane adhere to the surface of the wound to be treated. In addition, the collagen in the collagen gel can accelerate wound healing, and if it contains antibacterial agents, it can achieve antibacterial effects.

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 is composed 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, which has 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 whose entire volume is swelled by a fluid. The gel is semi-solid and does not have the characteristics of fluidity in a steady state. The gel that can be used in the present invention includes various types of copolymers, such as, but not limited to, polymer hydrophilic gels (hydrogel) [e.g., block copolymer Poloxamer 407, Poloxamer 181 , Pluronics L61; poly(acrylic acid), polymethylacrylic acid, polyacrylamide], multi-peptide gel [e.g., poly-L-lysine Acid (poly-L-lysine), poly-L-glutamic acid (poly(L-glutamic acid), collagen], polysaccharide gels (e.g., cellulose, starch, hyaluronic acid, alginic acid, Buttosan). In some embodiments, the block copolymer poloxamer 407 is used as the gel material. Poloxamer is a non-ionic triblock copolymer composed of polyoxypropylene linking two hydrophilic polyoxyethylene. It has an amphoteric molecular structure, which increases the water solubility of hydrophobic oily substances or the miscibility of different hydrophobic substances . In these embodiments, poloxamer 407 is combined with collagen to form a collagen gel.

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 some embodiments, nanosilver is added to the collagen gel of the present invention as an antibacterial agent.

As used herein, the term "artificial scab" refers to a scab structure formed by the biofiber membrane and collagen gel contained in the kit of the present invention, plus the protein in the subject's own wound tissue exudate. The bio-fiber membrane of the present invention has extremely high biocompatibility and is attached to the wound surface as an outer layer to isolate microorganisms. The collagen gel between the bio-fiber membrane and the wound, in addition to making the bio-fiber 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 become hard, forming a scab-like Layered, this is the artificial scab 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. Although the embodiments may only represent selected specific embodiments of the present invention, it should be understood that the following embodiments are illustrative and not restrictive.

Example

Example one Repair test of burn and scald on the inner side of human upper arm

Test material: The wound repair kit of the present invention contains bio-fiber membrane (pH value is about 7.0 +/- 1.0, water content is about 4%-20% (w/w), thickness is about 5-25 µm, base It weighs about 10~30 g/m ² , sterilized by high temperature, high pressure or γ-ray, and no heat source), and collagen gel (containing 100 µg/mL perch eel skin collagen, 180~200 mg/mL Polot Sham 407, 30 µg/mL nanosilver, prepared with sterile water).

Test object: A human subject (Mongolian race, male, 39 years old) suffered two burns and scalds on the inner side of his left arm with a medical cosmetic laser. 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-mentioned laser treatment, one wound was randomly selected as the control group, and only disinfected. The disinfection treatment method is: wash the wound with saline and wipe the skin around the wound with a disinfectant such as iodine solution; the other wound is In the test group, after the same disinfection treatment as the control group, the wound repair kit of the present invention was used for 25 days. The method is as follows: cut the required bio-fiber membrane to make the area 1~2 cm larger than the edge of the wound area to ensure It can cover the entire wound; after applying the collagen gel to any side of the bio-fiber membrane (the side that will be in contact with the wound) in a manner similar to applying glue, then apply the collagen gel to the bio-fiber membrane The surface was attached to the wound of the test group for a total of 25 days, during which the biofiber membrane was not replaced. Make follow-up observations and take photos for recording.

Result: as shown in Figure 1A to Figure 1F. The wound of the test group formed an artificial crust structure on the second day after the burn and scald, while the wound of the control group slowly formed a natural crust structure from autologous tissue (as shown in Figure 1A). On the 8th day, it can be observed that the artificial crust on the wound of the test group became thicker gradually and uniformly, while the wound of the control group formed a natural and uneven crust structure from autologous tissue. The crust around the wound was thicker and the wound The central crust is thinner (as shown in Figure 1B). On the 12th day, it can be observed that the artificial crust part of the wound in the test group is obviously hardened but the structure is still intact, while the natural crust structure formed by the autologous tissue in the control group is still uneven (as shown in Figure 1C). On day 25, the wound in the test group had healed until the artificial crust completely fell off, while the natural crust structure formed by autologous tissue in the control group was fragmented and partially peeled off, causing the wound to be exposed again and even infected and bleeding (such as Shown in Figure 1D). On the 53rd day, both the wounds of the test group and the control group had recovered, but obvious scar tissue was produced at the wound of the control group, while there was no such scar tissue at the wound of the test group (as shown in Fig. 1E). After tracking for 3 years, it can be observed that the test group has only partial pigmentation at the wound but the skin is flat, while the control group has obvious scar tissue formation in the wound, with a prominent granulation-like structure (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 a scab structure on human skin, shorten the wound healing time, and the wound scars after healing are not obvious.

Example two Repair test of abdominal pressure sore in Taiwan macaques

Test material: Same as Example 1.

Test subject: The animal case in this example is the primate Taiwanese macaque ( Macaca cyclopsis , male, estimated age about 25 years old) housed in the Wildlife Conservation Center (Pingtung, Taiwan), lying on his back for a long time due to his old age. Poor posture and pressure on the abdomen cause a large area of pressure sores. Clinical blood tests showed that this case had obvious inflammatory reaction and mild symptoms of anemia. In this case, there was diarrhea among the clinical symptoms, and a large area of the abdominal wound was obviously red and swollen.

Test method: First, clean the pressure ulcer in this case with saline solution, and wipe the skin around the pressure ulcer with iodine solution and other disinfectants; then, because the area of the pressure ulcer in the abdomen in this case is larger than the area of a single biofiber membrane, multiple sheets The bio-fiber membrane is used in a way that the boundary overlaps by 1~2 cm to ensure that the entire pressure ulcer wound can be covered; the collagen gel is applied to the inner surface of the plurality of bio-fiber membranes in a manner similar to glue application (will be in contact with the pressure ulcer wound) After that, the inner surface of the plurality of bio-fiber membranes coated with collagen gel was attached to the abdominal pressure ulcer wound in this case by overlapping the borders by 1 to 2 cm for 23 days. If it is serious, replace it with the wound repair kit of the present invention every 3 to 4 days. Carry out follow-up observations, observe once every 3 to 4 days, and take photos for recording.

Result: as shown in Figure 2A to Figure 2D. In this case, the abdominal pressure ulcer wound was obviously red and swollen before treatment (as shown in Fig. 2A), and the redness and swelling disappeared significantly on the 3rd day of using the wound repair kit of the present invention (as shown in Fig. 2B), and the pressure on the 12th day The area of the sore was reduced, and the redness and swelling of the wound had been greatly improved (as shown in Fig. 2C), and by the 23rd day, the pressure sore wound had been completely healed (as shown in Fig. 2D).

It can be seen that the wound repair kit of the present invention is convenient to operate, does not require frequent dressing changes, and can promote pressure ulcer wound repair to heal.

Example three Experiment on repairing tail trauma of wild Taiwan macaque

Test material: Same as Example 1.

Test subject: The animal case in this example is a primate Taiwanese macaque (male, age unknown) housed in the Wildlife Conservation Center (Pingtung, Taiwan). The tail was severely injured and infected due to fights or other accidental factors. ulcer.

Test method: First, clean the tail wound in this case with saline solution, and wipe the skin around the wound with iodine solution and other disinfectants; then, apply collagen gel to the inner surface of the biofiber membrane in a manner similar to that of glue. After the side where the tail wound is in contact), the inner surface of the bio-fiber membrane coated with collagen gel is attached to the tail wound of the case, and the outer layer of the bio-fiber membrane is covered with gauze to prevent the case The bio-fiber membrane fell off due to activity. Due to the serious wound infection, the wound repair kit of the present invention was replaced every 4 days, and follow-up observation and photographing were performed.

Result: 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), and the tissue growth recovered after the 30th day using the wound repair kit of the present invention (as shown in Figure 3B) to the 50th day At this time, the exudation of the tail wound has been significantly reduced (as shown in Fig. 3C), and the skin surface layer has been completely repaired on the 75th day (as shown in Fig. 3D).

It can be seen that the wound repair kit of the present invention is easy to operate, even if it is used on severely infected wounds, it does not require daily dressing changes, which can reduce the frequency of dressing changes and promote the repair of severely infected wounds.

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

In summary, the technical features disclosed in this case have fully met the statutory requirements for invention patents for novelty and advancement. I filed an application in accordance with the law, and I implore your bureau to approve this invention patent application to encourage invention.

Figure 1 shows the results of a burn and scald repair test on human skin. 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. means the control group; Exp. means the test group.

Figure 2 shows the test results of abdominal pressure sore repair in Taiwanese macaques. Figure 2A shows the redness and swelling of the pressure ulcer before treatment. The left photo is the front view, and the right photo is the side photo; Figures 2B to 2D show the pressure ulcer on the 3rd, 12th, and 23rd day after treatment, respectively In the recovery situation, the left picture is a front view, and the right picture is a side view.

Figure 3 shows the results of the repair test of tail trauma in wild Taiwanese macaques. Figure 3A shows the condition of the tail infection ulcer 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 (5)

A wound repair kit for producing artificial scabs, including a bio-fiber membrane and a collagen gel. The collagen gel contains about 50-250 µg/mL collagen and about 150-250 mg/mL gel. Glue, and about 0-50 µg/mL antibacterial agent. A patch for producing artificial scabs, 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 gel layer is It is used to contact with a user and make the bio-fiber membrane stick to the user. The patch according to claim 2, wherein the collagen gel contains about 50-250 µg/mL collagen, about 150-250 mg/mL gel, and about 0-50 µg/mL antibacterial agent. A use of biological fiber membrane and collagen gel in preparing artificial crust for treating wounds. The use according to claim 4, wherein the collagen gel contains about 50-250 µg/mL collagen, about 150-250 mg/mL gel, and about 0-50 µg/mL antibacterial agent.

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