TWI247614B - Wound dressing - Google Patents

Abstract

The present invention provides a wound dressing for wrapping a wound on the surface of a living creature. The wound dressing at least includes more than two layers of a synthetic dressing, which consists of an air-permeable, waterproof, antibiotic upper layer for contacting with the atmosphere, and a liquid-permeable and wound-healing-promoting lower layer for contacting the wound. Each layer construction of the wound dressing further includes a nano metal particle dispersed therein for enhancing the antibacterial power or the regeneration rate of the wound cells.

Description

1247614 V. INSTRUCTION DESCRIPTION OF THE INVENTION (1) Field of the Invention The present invention relates to a multifunctional wound dressing. More particularly, the present invention relates to a synthetic wound dressing having a multi-layer structure which is breathable but impervious to water and has various features which prevent invasion of foreign bacteria, reduce wound scarring and promote wound healing. Prior art

The skin has a total area of 1. 5~2. 0 m ^ 2 . The skin generally has the function of regulating body temperature and regulating water to avoid dehydration, and is also the primary line of defense against foreign pathogens. When the skin is injured, it may cause imbalance in body function, severe organ imbalance, and even death. Inflammation, ulcers, trauma, burns, surgery, and congenital malformations cause skin defects and abnormalities, which not only cause physical pain to the patient, but also often cause trauma to the patient at every stage of treatment. According to relevant information, there are about 3,200,000 patients in all types of patients in China who need to transplant their skin every year. At present, autologous skin transplantation is used. In the United States, there are about one million burns per year, and the average injured area accounts for 14% of the total body surface area. About 2 3,300 burned patients must live in the United States. A burn-and-burn center, in which about 2,760 patients were severely burned. It is estimated that the average hospitalization cost per scald patient in the United States is 60,000 to 80,000 US dollars per year, and the amount of medical treatment for each patient from the beginning of treatment to wound healing ranges from US$36,000 to 117,000. . In addition to burns, there are 20 to 400,000 people in the United States each year suffering from diabetes due to diabetes, and about 700,000 people suffer from venous ulcers, about 150,000 people.

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Page 4 1247614 V. Description of invention (2) Suffering from hemorrhoids. These patients, due to their insufficient ability to regenerate, need to obtain skin from outside the body for transplantation. According to statistics, there are 15,000 burn patients in Sakamoto who need skin transplants every year. In Taiwan, there are more than 2,000 burned patients every year, and about one-tenth of them are large-scale burns. In addition, according to the statistics of the Department of Health, the amount of health care for skin-related diseases in the year of 2 〇 〇 is about NT$100 million.

Normally, normal people can usually heal a small area of the wound themselves. However, for a large area of burned patients, the skin of the patient's own body is usually cut to a thickness of about 0 · 0 14 inches, and the machine is opened by a machine. 2 times, covered in the injured area 'also known as multi-layer skin autograft thickness skin autograft). However, patients with large areas of injury have limited skin left, or when the patient's wound regeneration ability is weak, such as digging the east wall to supplement the Western Wall in this way, it is no different. In patients with deeper wounds and poor skin healing, such as ulceration of limbs in diabetic patients, in addition to using antibiotics to stop infection, it is usually necessary to use allogeneic skin grafts. In terms of the source of the skin, from the 1950s, some people tried to make the skin of the allogeneic skin transplant.

Years to the present, the skin of the dog was used in 1966, the material to be transplanted in 1965, and the use of the skin was improved as a heterogeneous skin. Currently, the pigskin or cowhide structure is similar. Use radiation to animal skin, the most commonly used pig skin as disinfection and freezing as artificial skin for pig artificial skin, dry, to skin, the source of the skin, because it needs to remove the low antigenicity mostly from humans and humans After the skin remains, the fine cells are suppressed at the same time.

1247614 V. INSTRUCTIONS (3) Bacterial growth. This type of artificial skin is often used as a temporary covering for 2 degree burn wounds. It can be used for up to 10 days. The disadvantages are radiation treatment and cold; the east drying treatment is quite expensive. In order to improve this shortcoming, some people have developed a method of saving and saving. There are not many products on the market, mainly Bi〇c〇re.

Medical Technologies (Topeka, KS, U.S.A)

The MedifiITM &SkinTempTM developed by KollagenTM technology is a method in which the type I collagen of the cow is reconstituted and applied to the wound in the form of a gel or dressing, which promotes the healing of the surface wound. The speed is about 3 weeks faster than the traditional way. In addition, g γ n a c 〇 L L· A G ' (Hehsau, Switzerland) uses the gel f protein extracted from the bovine heel bond to produce a collagen membrane, which can be used to promote wound healing. h The advantage of Bayden or Irritable Skin Transplantation is that collagen is not derived from the compatibility of the material; however, the skin inside the skin needs to be treated in a specific way: (乂 乂 xenograft antigenic substance f, ( 2) Skin from animal sources can be caused by Z in the skin, and (3) Treated animal skin::: Protein shell disease often falls off. Anti-.,,,,,,,, In order to solve the above-mentioned heterologous skin transplanted allogeneic skin for transplantation, generally use '·, ']', it is proposed to use the same human corpse or fetal amniotic membrane, advantage 2 Ζ ί ΐ 皮肤 皮肤 皮肤 , , , , , , The tissue-compatible lack of $ in its treatment is less than the skin is from the amnion or corpse 吏: the second is: (1) the lack of skin in Taiwan also has the risk of infection, 2 human allograft and (3) allogeneic dermal transplantation also 1247614

, invention description (4), artificial immune rejection in 2000. To avoid the potential risk of disease infection Skin grafting is another option for wound treatment, and the market for artificial skin is estimated to be approximately $4.3 billion. The most common type of general burn wound treatment is a synthetic dressing because it is simple to manufacture and easy to obtain. The material used must be a neutral material. Synthetic dressings can be attached to the wound, have elasticity, allow the wound fluid to flow out, and avoid bacterial infections, so the products on the market are also the most. Most of the materials used in synthetic dressings are water-based, polyaminoguanidine.

Polyurethane film, p〇lypeptide 4 chemically synthesized polymers (such as nylon) are mainly non-biodegradable materials. Covered with silicone rubber, the inner layer contains antibiotics, which is more suitable for superficial wounds. The wound healing time ranges from 7 to 5 days, and the wound can be removed after healing. In the past years, 'the use of tissue engineering methods to develop artificial skin technology has progressed rapidly, but it is still limited to the epidermal tissue and connective tissue of the skin. No matter which type of artificial skin is used, the preparation process is long, the method is cumbersome, and the price is inconvenient. 'Generally, it takes 1 to 2 months to make the wound more a, and it also meets the needs of patients with various skin defects. Therefore, there are still many spaces that can be changed by artificial skin itself, including increasing its adhesion to wounds, preventing bacterial invasion and growth, increasing elasticity and ductility, increasing shelf life, not being immune-rejecting, and allowing water and gas to seep. =, internal pore size can allow cells to move, using biodegradable materials enamel, material compatibility, non-toxic, easy to store, reduce wound scarring, shorten wound healing time and reduce prices.

Page 7 1247614

Disclosure of the Invention The object of the present invention is a dressing for accelerating cell growth to promote the invasiveness of foreign bacteria to prevent wound infection. The more it is. Speed, and Effective Resistance Another object of the present invention is to link wounds that are also degradable and non-toxic. Another object of the present invention is to provide a wound dressing that provides a cumbersome manufacturing procedure. The present invention is inexpensive and does not require the present invention to achieve the object of the present invention by having a different characteristic mouth dressing. The wound dressing gas as directed by the present invention passes through an upper layer that is impervious to water and an underlying layer of a growing environment. The composite material comprises a plurality of layers of wound material, which comprises at least one layer which can make the water absorbent and can provide the cells. The above-mentioned wound can be constructed to promote the upper layer of the cells to be separated from the upper layer, and the wound is Prepare, above the protective film, for the skin after the wound is regenerated, the lower layer can be healed. The above layer can be used to prevent the skin from replacing the fine environment and easily peeling off the upper layer. The example is a temporary infection layer with a cell regeneration space. Without a middle layer, it can make the sub-packages, the body, and the body, and promote the damage layer. It is easy to replace the layer with the epidermis, which is used for liquid loss and bacterial invasion. The lower three-dimensional spatially porous formation of the wound is healed and provides a detachment of the upper layer from the underlying layer for the purpose of facilitating the newly formed tissue on the outside. Aqueous polymer to urethane

Page 8 1247614 V. Inventions (6) (polyurethane, PU) and silicone, but not limited to this. In order to provide the upper layer with better gas permeability, elongation and elasticity, it can be prepared using a porous polyurethane. As the lower layer described above, it can be prepared using a hydrophilic polymer, and examples thereof include a copolymer of chitosan and chi tosan/alginate, a gelatin, Polylactic acid, polyglycolic acid, copolymer of ethanolic lactic acid and lactic acid, copolymer of lactic acid and aminocaproic acid, poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate) and 3-hydroxyvaleric acid A copolymer of an ester, but is not limited thereto. It can be prepared by using hydrating gel or polyacrylic acid (PAA). In order to strengthen the antibacterial effect of the upper layer, i, Du., and Yihuahua can further add a plurality of nano metal particles to the upper layer. In order to obtain a preferable particle size of the metal particles, it is preferable that the particle size of the metal particles is too small, and the metal particles of the rice may be exemplified by r and only. The nanoparticles described herein promote wound healing, healing, and the like, but are not limited thereto. The addition of a plurality of nano-metal particles in the lower layer can further increase the growth rate of the cell, and the nano-metal is preferred to promote fineness of 40 nm. The size of the nano metal plate described herein is preferably such that gold is gold, but is not limited thereto. The invention may be exemplified by reference to the following description of the embodiments, which are not intended to limit the scope of the invention and the embodiments of the invention. The content revealed by the face. Within the scope of the invention. Improvement and modification, but still not off

$9页 1247614 V. DESCRIPTION OF THE INVENTION (7) Embodiments Wounds 咅J 咅 Ϊ 具有 Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ Ϊ 伤口 伤口 伤口 伤口 伤口 伤口 伤口 伤口 伤口;=接: and blocking the invasion of foreign bacteria, i square layer (1): the layer, as: the limb permeability 'can be used as a temporary epidermal ^ invasion. Below 'to prevent infection, loss of body fluids and fluid permeability of the bacteria ^ for contact with skin wounds, both

C environment, available as a skin substitute layer. The wound dressing (丨) is aged, 々 has porosity, and can make the gas sputum, the south, the eve, and the breast permeable. The upper layer can be prepared by using the material of _β S L through the material (1). In order to make the wound cost IT, i V the despicable ductility of the field can be better prepared by H ^ @ ; σ Guan Lang's bend, the upper layer (11) ϋΐ ? Further, it is preferable that the lower layer (12) of the Tibur production has a three-dimensional inter-dimensional porous structure. = Silver metal _ has a bacteriostatic effect, especially silver. Therefore, in order to make the upper screen + α tamping h people ~ from the tens of thousands of layers U 1 ) have a more antibacterial effect, can be further

v Incorporating silver nano-particles (13) into the upper layer (11), the bacteriostatic ability of the square layer (11).苴中此1 is preferably 1~4 0 0 nm, and the doping amount of nano silver in the upper layer is %

1~20% of the total amount of the upper layer dressing. / π I in addition to the ability to accelerate wound soreness. Incorporating gold nano-particles (1 4 ) to strengthen the lower layer (1 2) to promote cells

1247614 V. Description of invention (8)

The ability to grow. Wherein the total yield of the nano gold is 1 ... m' and the total amount of nanometer ^^= in the lower layer is 1 to 20%. On the other hand, it is easy to peel off on the outer side without damaging the lower part; 彳1 2彳€, 曰后可,隹^^^ Λ, the new tissue of the uU Further, the upper layer (21) and the lower layer (22) may be further added to separate the upper layer (21) from the lower layer (22), and the upper layer may be easily peeled off after healing. Finally, in the wound, reference is made to the second figure, which is a schematic view of another embodiment of the wound dressing according to the present invention. For /, there is 夕 ^,,,. The structure can be as shown in the second figure (not 23 with; raise; love again brother, need a second lower layer (24). As mentioned above, the first --) then join (2) ^ Fang 2 (2)) is doped with a plurality of nano metal particles (25). In addition, in order to enable the dressing (7) to provide a better effect of promoting wound healing, a plurality of nylon particles can be incorporated into the lower layer (2 3 ) (24) of the first (2, 6) Spiritual and technical features, in order to make the invention τί:: 知 知 , , , , 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔Or the copolymer of two & to prepare the underlying layer (22), which is illustrated by an example of the polyacrylic acid intermediate layer (23)' to further illustrate the technical content of the limb of the present invention. The above wound dressing having a multilayer structure in which polyacrylic acid can be used

嶋

II 1^· Page 11 1247614 V. INSTRUCTIONS (9) 7'-ray (r-ray) irradiation is carried out by graft polymerization to make it conform to the square and porous polyurethane. surface. Further, chitosan and/or alginic acid or a copolymer obtained by copolymerizing the two, anthraquinone (1-ethyl-3-(3) with 1-ethyldimethylaminopropyl) -dime1:hyaniino propyl) carbodiimide (EDC) is attached to a porous polyurethane having a polyacrylic acid attached to the surface to form a multilayered wound dressing. Example 1

Preparation of multi-layered wound dressings, an appropriate amount of polyurethane (Pel 1 ethane 2363-8 0A) is prepared in tetrahydrofuran (THF) &gt; trough to prepare a 1% (w / v) polyurethane solution, and A sodium chloride particle (<2 &amp;#m) was added in a weight ratio of 0 · 5 8 L to polyamine g. After that, pour the bath into the Teflon tray, at 6 〇 to 6 5, and evacuate until the mixture is completely drained. The dried polyurethane film was further washed with deionized water at 80 ° C for 24 hours to remove sodium chloride. Finally, it is dried to cast a porous polyurethane film. The porous polyurethane film is placed in a solution of different acrylic acid (AA) (10 ～40 wt%), and the ray makeup is rubbed at 6 〇c to form a graft polymerization reaction. . After the graft polymerization was completed, the film was washed with deionized water for 24 hours to remove unreacted monomers or homopolymers. The chitosan was dissolved in 1% acetic acid solution to prepare 1% chitosan. In addition, the seaweed gum salt was dissolved in deionized water to prepare a 1% solution. Mixing the two solutions, then pouring them into the above-mentioned modified acrylic acid

Page 12

1247614 V. INSTRUCTIONS (10) Acid: In the container of the film, add ethyl ethyl bromide (3~ dimethyl acid water gel:), and the diimine (smelling 'succinimide chemically fixed to propylene drying) After y, ί, the sample is cold-dried at ~2〇°c. It is prepared to have a multi-layered enamel solution. The solution is cross-linked. The second embodiment of the multilayered wound dressing containing nano-gold particles is prepared. Preparation

祥取—Charcoal (Pellethane 2363-80A) is prepared as a 1% by weight (w/v) polyamine phthalate solution with tetrachloroguanidine (THF) and gluten, and added to 〇·5 ~8 times - sodium chloride particles (&lt;25 //m) relative to the weight ratio of polyurethane. Then, take this solution and pour it into the Teflon tray at 60 °C to 6 °C, and evacuate until the whole process is dried. The dried polyurethane film was further washed with 80 C of deionized water for 24 hours to remove sodium chloride. Finally, it is dried to cast a porous polyurethane film. The above porous polyurethane film is placed in a different acrylic acid (AA) (10 to 40 wt%) solution to 60 C 〇 r ray

Fc, shot to carry out graft polymerization. After the graft polymerization was completed, the film was washed with deionized water for 24 hours to remove unreacted monomers or homopolymers. Chitosan was dissolved in 1% acetic acid solution to prepare 1% chitosan. In addition, the seaweed gum salt was dissolved in deionized water to prepare a 1% solution. The two solutions were mixed, and then an aqueous solution of 1% (w/v) of nano gold particles was added to make the concentration of the nanoparticles in the mixture (K 1 % (w/v), and then

Page 13 1247614

Two nights: into the above... dilute acid modified polyamine methyl group == two bismuth: - (3 dimethylaminopropyl) carbonized di-Asian female (EDC) 'will be fixed in butanol chemically fixed in acrylic acid water Thereafter, the sample was frozen at -20 ° C to obtain a wound dressing of a calcium carbonate (CaC 12) solution for cross-linking, anti-depot, and L-form. …reaction. The wound dressing prepared in the multilayer structure of the first embodiment and the second embodiment was prepared by sterilizing with a 70% aqueous solution of ethanol, and then using a phosphate buffer solution. (PBS, ρ Η = 7.4) Wash several times until the ethanol is completely removed. The sterilized wound dressing is then placed in a 24 well (w e 1 1) cell culture chamber to complete the film sterilization step. &lt; In addition, the piglet chondrocytes (passage 2) were incubated with 0.25% trypsin (the second generation) to form a cell suspension, and the cell suspension was further incubated at 2 rpm. After centrifugation, the supernatant was removed, and then d μ ε Μ (Dulbecco's Modified Eagle Media) medium was added to prepare a cell suspension of 5 Χ 1 Ο 4 ce 1 1 s / m 1 . The above cell suspension was added to each well by adding 1 ml, and then cultured in an environment of 5% CO 2 and 37 ° C, and taken out for cell attachment and growth test after 72 hours. Referring to the third figure, the effect of adding nano metal particles on the growth of the wound dressing promotes cell growth. It can be seen from the third figure that after the cultivation of the cockroach,

1247614 V. INSTRUCTIONS (12) The cells can proliferate to about 4 to 5 times, wherein the number of cell attachments in the group of added nano metal particles is significantly higher than that of the group of non-added nanoparticles, showing the present invention. The wound dressing containing the nano metal particles indicated has better cell adhesion and cell growth promoting effect, and it is speculated that the surface may be formed into a nano surface (nano roughness) by adding nano gold particles to the cell physics. Stimulation, thus promoting cell growth.

Page 15 1247614 BRIEF DESCRIPTION OF THE DRAWINGS The first figure is a schematic illustration of a wound dressing having a multilayer structure as indicated in accordance with the present invention. The second figure is a schematic view of another embodiment of a wound dressing having a multilayer structure as indicated in accordance with the present invention. The third picture shows the effect of adding nano metal particles on the growth of wound dressings to promote cell growth.

Component Representation Symbol 1 Injury V Dressing 11 Upper Layer 12 Lower Layer 13 Intermediate Layer 14 Nano Metal Particles 15 Nano Metal Particles 2 Injury α Dressing 21 Upper Layer 22 Intermediate Layer 23 First Lower Layer 24 Second Lower Layer 25 Nano Metal particles 26 nano metal particles %

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Claims (1)

1247614 I ψ Case No. 92112116 Amendment of patent application scope 1 · Kind of compounding and regenerative 2. 2. Shennai 3. Such as Shen Nai 4. Such as dressing material 5 · such as Shen dressing 6 · Such as Shen layer 7 The ring of the dressing 8 ·If the application is strong and used for the dressing and the number of the ring, the patented metal particles of the bulk material, please patent the metal piece, please have more patents, patents, flexible, patented materials. The invention relates to a wound dressing having a patented three-dimensional and empty patenting function, which at least comprises: contacting the outside air and blocking the contact of the outer layer of the invasive skin wound, and providing a lower dressing layer for regenerating the cell growth space; a metal metal particle which is doped into the wound dressing, and is used in the upper layer dressing to strengthen the upper layer of bacteria, and the lower layer of the dressing layer is used to promote the growth rate, Accelerate wound healing, and the nano-gold material is selected from the group consisting of gold and silver. The wound dressing of claim 1, wherein the plurality of granules have a size of from 1 to 400 nm. The wound dressing of claim 1, wherein the plurality of grains are doped in an amount of up to 20% of the total amount of the upper layer dressing. The wound dressing of clause 1, wherein the upper layer is porous, which allows gas to pass but is impervious to water. The wound dressing of claim 1, wherein the upper layer and the extensibility. The wound dressing of any of clauses 4 or 5, wherein the upper is self-porous polyamino phthalate or tannin. The wound dressing of claim 1, wherein the underlying spatially spatially porous structure is for providing a cell regeneration compartment. The wound dressing of claim 1, wherein the lower layer Page 17 1247614 Case No. 92112116 Revised 々, Patent Range The dressing is biocompatible, biodegradable and non-toxic. 9. The wound dressing according to claim 7 or 8, wherein the underlayer dressing is selected from the group consisting of a copolymer of chitosan and alginic acid, a gelatinous substance, a polylactic acid, a polyglycolic acid, and an ethanolic lactic acid. Copolymer with lactic acid, copolymer of lactic acid and aminocaproic acid, poly(3-hydroxybutyrate) or copolymer of poly(3-hydroxybutyrate) and 3-pentyl valerate. 1 0. A wound dressing having a strengthening function, comprising at least: an upper layer dressing for contacting external air and blocking invasion of foreign bacteria; a contact with the skin wound and providing a space for regenerating cells and environment a lower dressing layer; an intermediate layer dressing for easily peeling the upper layer dressing from the underlying layer dressing; and a plurality of nano metal particles doped into the wound dressing, wherein The upper layer dressing is used to strengthen the antibacterial property of the upper layer dressing, and the lower dressing layer is used to promote the growth rate of the regenerated cells to accelerate wound healing, and the material of the nano metal particles is selected. A group of gold and silver. 1 1. The wound dressing of claim 10, wherein the plurality of nano metal particles have a size of from 1 to 400 nm. 1 2. The wound dressing of claim 10, wherein the doping amount of the plurality of nano metal particles accounts for 20% of the total amount of the upper layer dressing. Page 18 1247614 Case No. 92112Π6 修正 Amendment VI. Scope of Patent Application 1 3. The wound dressing of claim 10, wherein the upper layer dressing is porous, which allows gas to pass but is impervious to water. 1 4. The wound dressing of claim 10, wherein the upper layer dressing is elastic and extensible. The wound dressing of claim 13 or claim 14, wherein the upper layer dressing is selected from the group consisting of porous polyurethanes or silicones. 1 6. The wound dressing of claim 10, wherein the underlying dressing has a three dimensional spatial porous structure for providing an environment and space for cell regeneration. 1 7. The wound dressing of claim 10, wherein the underlying dressing is biocompatible, biodegradable, and non-toxic. The wound dressing of claim 16 or 17, wherein the underlayer dressing is selected from the group consisting of a copolymer of chitosan and alginic acid, a gelatinous substance, a polylactic acid, a polyglycolic acid, a copolymer of ethanolic lactic acid and lactic acid, a copolymer of lactic acid and aminocaproic acid, a poly(3-hydroxybutyrate) or a copolymer of poly(3hydroxybutyrate) and 3-hydroxyvalerate. The wound dressing of claim 10, wherein the intermediate layer dressing is selected from the group consisting of hydr ge ge 1 or polyacrylic acid ( PAA ) o 2 〇. The wound dressing of claim 1, wherein the intermediate layer dressing is attached to the surface of the upper layer dressing by graft copolymerization. 2 1. The wound dressing of claim 10, wherein the wound Page 19 1247614 Page 20