TWM592764U - Anti-stick patch for promoting wound healing, anti-inflammatory and degradable in vivo - Google Patents

Abstract

The present invention provides an anti-sticking patch that promotes wound healing, anti-inflammatory and degradable in vivo, including: a main body layer, the main body layer is a single-layer sheet body, and has a plurality of pores, wherein the main body layer contains silk protein and hydrophilicity Polymer material, and the silk protein contains silk fibroin. The hydrophilic polymer material is a biodegradable biodegradable polymer. Because silk protein has the effect of promoting wound healing and anti-inflammatory, it is more Help patients recover after surgery.

Description

Anti-sticking patch that promotes wound healing, anti-inflammatory and degradable in vivo

The present invention provides an anti-sticking patch that promotes wound healing, anti-inflammatory and degradable in vivo, especially a degradable anti-sticking patch made of silk protein and hydrophilic polymer materials.

"Sticky" refers to the specificity of the body tissues during wound healing, based on the lack of specificity for white blood cells, fibroblasts or fibrin when the inflammatory reaction occurs, which only targets the wound itself, resulting in a normal tissue near the wound. They are also glued together to form "internal scars", which can further lead to complications such as obstruction of the small intestine, which has a huge impact on the patient's physical health after surgery.

In order to avoid the above-mentioned adhesion problems, anti-adhesion patches are medical devices commonly used in abdominal and gynecological operations in recent years. At present, there are two common types of patch-type anti-sticking products on the market: cellulose and hyaluronic acid, and depending on the material, there are different prices and properties, such as: patch decomposition time, and use restrictions. In view of the fact that there are many factors that affect the adhesion of patients, such as personal constitution, anti-adhesion patches with new materials are provided to provide patients with more diverse options to reduce the risk of "sticking" and its complications , And add anti-inflammatory function, it will have its necessity and importance.

In view of the fact that the anti-adhesive patches available on the market only have a single function of preventing tissue adhesion, the present invention also provides a multi-functional anti-adhesion patch that promotes wound healing, anti-inflammatory and prevents tissue adhesion, that is, borrowing The silk protein itself has the effects of promoting wound healing and anti-inflammation, so that the novel material is more conducive to the rehabilitation of patients after surgery.

The present invention provides an anti-sticking patch that promotes wound healing, anti-inflammatory and degradable in vivo, including: a main body layer, the main body layer is a single-layer sheet body, and has a plurality of pores, wherein the main body layer contains silk protein and hydrophilicity A polymer material, and the silk protein contains fibroin. The hydrophilic polymer material is a biodegradable polymer with biocompatible properties.

Preferably, the body layer has a foam structure.

The new model uses silk protein and polymer materials compatible with silk protein, and can form a "single layer" sheet body with uniform texture and contains multiple pores. Therefore, the structure of this new model is affected by the selected material and silk protein Affected by compatibility. In fact, it can be found from the subsequent embodiments that the manufacturing method can affect the bulkiness and bubble structure of the body layer, so that the body layer has different degrees of porosity and texture.

As mentioned in the prior art, surgery will cause adhesion to the organs or tissues around the wound due to fibrin hyperplasia, so this new type is to physically block the wound and the surrounding organs or tissues to avoid adhesion, and It further reduces the risk of sequelae caused by tissue or organ sticking and the health damage and inconvenience that requires a second surgery.

In addition, based on the anti-sticking property of the new type, it can also be used to replace gauze, and is suitable for post-operative wound care. This not only avoids the secondary injury caused by tearing the sticky part of the wound during dressing change, but also reduces The pain of dressing change.

Finally, because the new type uses natural silk protein, it has anti-inflammatory and accelerated wound healing effects, so it has triple effects of anti-inflammatory, accelerated healing and anti-sticking, which is highly competitive in the market and is not used in the market. Such novel materials are used as anti-sticking patches, so the materials selected for this creation are further improved for the material itself and structure, which is progressive.

Preferably, the single-layer sheet is an opaque, transparent or translucent film.

In one embodiment, the single-layer sheet is a thin film and has a soft texture, which can be easily attached to the affected part. Preferably, the color of the single-layer sheet is beige.

More preferably, the single-layer sheet-like body of the main body layer has a length of 60 to 90 mm (mm) and/or a width of 60 to 90 mm and/or a thickness of 0.7 to 1.3 mm. Even more preferably, the length is 75±2 mm and/or the width is 75±2 mm and/or the thickness is 1±0.2 mm.

In another embodiment, the single-layer sheet-like body is a thin film, and its color is transparent or translucent, preferably transparent yellowish.

The anti-adhesive patch of the commercially available product "Gainake An Dexi" (Health Department Medical Device No. 014171) is made of oxidized regenerated fiber, and the product itself is not transparent, and has the disadvantage of not easy to observe the wound condition . In contrast, the anti-adhesive patch that can be degraded in vivo can be designed as a transparent or translucent anti-adhesive patch, so it has the advantage of easy observation of wounds.

More preferably, the single-layer sheet-like body of the body layer has a length of 90 to 110 mm and/or a width of 120 to 140 mm and/or a thickness of 0.2 to 0.8 mm. Even more preferably, the length is 100±2 mm and/or the width is 130±2 mm and/or the thickness is 0.5±0.2 mm.

In one embodiment, the single-layer sheet is a round or square film, and its color is transparent. The diameter of the round film is 15 to 40 mm; the length and/or width of the square film is 100 to 150 mm; and/or the thickness of the round or square film is less than 1, 0.5 or 0.1 mm.

In another embodiment, the single-layer sheet-like body is a white thick film, and the thickness is 1.5, 2 or 2.5 mm or more; preferably, the thickness is 1.5 to 3 mm.

Preferably, it further includes two cover layers, which are respectively disposed on both sides of the main body layer to form a three-layer structure.

Preferably, the material of the cover layer is polyvinyl alcohol (PVA), polyethylene glycol (PEG/polyethylene oxide, PEO) or polyethylene (PE).

In one embodiment, the three-layer structure has a length of 40 to 80 mm and/or a width of 40 to 80 mm and/or a thickness of 1 to 2 mm. Preferably, the thickness of either of the two cover layers is 0.2 to 0.5 mm, and the body layer is 0.6 to 1 mm.

In another embodiment, the three-layer structure has a length of 70 to 200 mm and/or a width of 50 to 130 mm and/or a thickness of 1 to 2 mm. Preferably, the thickness of either of the two cover layers is 0.2 to 0.5 mm, and the body layer is 0.6 to 1 mm.

In one embodiment, the body layer can be prepared using freeze-drying technology or casting technology.

Preferably, in the preparation of the main body layer or in the manufacturing process, no cross-linking agent or no cross-linking agent may be added, so as to avoid the doubt of derivatizing biocompatibility after the material is modified; In addition, ultraviolet irradiation is used to avoid further chemical bonding between different materials, thereby changing the degree of crosslinking of the materials, affecting the density and internal structure of the finished product, and thus saving process time.

More preferably, the body layer does not change the structure of the finished product due to the irradiation of gamma rays, but can be sterilized using gamma rays.

In another embodiment, the main body layer is made of silk protein, hydrophilic polymer material and solvent, and the solvent is removed during the preparation process. Preferably, the material of the finished body layer includes silk protein and hydrophilic polymer material.

The present invention also provides a silk protein whose raw material is selected from any one or a combination of water-soluble silk protein, silk protein powder ingot and silk protein stock solution.

Preferably, the water-soluble silk protein is a dilution of the silk protein extract; the silk protein powder ingot comprises silk fibroin and sericin, and both the silk fibroin and sericin contained in the silk protein powder ingot The total weight is the basis, the silk fibroin is 98 wt%, and the sericin is 2 wt%; the silk fibroin and sericin contained in the silk fibroin stock solution are based on the total weight of the two, and the silk fibroin is 76 wt%, sericin is 24 wt%.

Silk proteins generally have two main molecular conformations of secondary structure: 1. Silk I (Silk I) has random coil and α-helix structures, is soluble in water and is not Crystalline form; and 2. Silk II (Silk II) has β-sheet (β-sheet), and is composed of anti-parallel β-sheet layer, has high stable structural properties, insoluble in water or neutral salts , But soluble in strong acid or alkali; silk I can be transformed into silk II after being treated at high temperature above 180°C. The above three silk protein raw materials have not been treated at a high temperature above 180°C, so the silk protein contained in it still has the main configuration of silk I and is water soluble.

To further explain, silk fibroin has the function of accelerating cell repair, and has high biocompatibility, and can be degraded in the body; sericin has strong moisturizing properties, and is usually used as a cleanser for the body surface. In order to promote wound healing, anti-inflammation and anti-sticking patches that can be degraded in vivo, the silk fibroin component of the silk protein components used in the patch will be significantly higher.

Preferably, the amino acid component of the silk protein contains at least: Alanine, Arginine, Aspartic acid, Glutamic acid, Glycine ( Glycine), Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline ( Proline, Serine, Threonine, Tyrosine, Valine, and Tryptophan, and various amino groups detected by the silk protein The total weight of the acid content is based on alanine (Alanine) content of 25 to 30%, glycine (Glycine) content of 33 to 39%, serine (Serine) content of 9 to 15% and / Or the content of Tyrosine is 7 to 13%.

In one embodiment, based on the total weight of various amino acids detected by the silk protein, the content of thiamine-containing acid in the silk protein is less than 1%; preferably, the content of the silk protein The content of thiamine is less than 0.1%.

More preferably, the cystine acid content of the silk protein is not detected, and based on the total weight of the various amino acid content detected, the methionine content is less than 1%. Even better, the methionine content is less than 0.1%, 0.09%, 0.08%, or 0.07%.

In one embodiment, the biocompatible biodegradable polymer used in the novel is selected from polyvinyl alcohol (PVA), polyethylene glycol (PEG/polyethylene oxide, PEO), Starch, collagen, gelatin, hyaluronic acid, polyvinylpyrrolidone (PVP) and carboxymethyl cellulose (CMC) or any of them Of the combination. More preferably, since chitosan may easily cause allergic reactions to people who are allergic to seafood, the new anti-sticking patch may or may not contain chitosan.

Preferably, the molecular weight of the biocompatible biodegradable polymer is between 10,000 Dalton and 400,000 Dalton.

More preferably, the biocompatible biodegradable polymer is polyvinyl alcohol (PVA) with a molecular weight of 12,000 Daltons to 74,800 Daltons, and/or a degree of polymerization of 295 to 1700.

In another embodiment, based on the total weight of the two raw materials of the silk protein and the hydrophilic polymer material, the weight percentage of the silk protein is 60 to 90%, and the weight percentage with the hydrophilic polymer material is 10 to 40%.

Preferably, the concentration of the raw material of the anti-sticking patch is respectively: the concentration of the silk protein is 50 to 120 mg/ml or the concentration by weight is 5 to 12%, and when the hydrophilic polymer material is polyvinyl alcohol ( Polyvinyl alcohol (PVA), the weight percent concentration of the polyvinyl alcohol is 5 to 10%; when the hydrophilic polymer material is polyethylene glycol (polyethylene glycol, PEG), the polyethylene glycol (polyethylene glycol , PEG) is 2 to 4.5% by weight, or when the hydrophilic polymer material is polyethylene oxide (PEO), the weight percentage of polyethylene oxide (PEO) The concentration is 0.15 to 1%.

In the novel anti-adhesive patch that can be degraded in vivo, the body layer can be prepared by the following steps: (a) The silk protein and the hydrophilic polymer material are mixed uniformly to form a mixed solution of the silk protein hydrophilic polymer material; (b) freeze-drying the silk polymer hydrophilic polymer material mixture at a freezing temperature of -25°C or lower to form a frozen silk protein mixture; and, (c) After the frozen silk protein mixture is dried, the whole piece is stripped to form the main layer.

Preferably, the above freezing and drying steps are performed sequentially or simultaneously.

In one embodiment, the "freeze-drying" step refers to evacuating in a low temperature range below 0°C for drying purposes.

Preferably, the freezing temperature is any one of -26°C, -30°C, -40°C, -50°C, -60°C, -70°C, -80°C, -90°C, -100°C, etc. The interval formed by any two, or any value within the interval formed by any two of its equivalent values.

Preferably, the freeze-drying time is 1 to 28 hours, more preferably 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17. 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 hours, the interval formed by any two of its equivalent values, or any value within the interval formed by any of its two equivalent values.

Preferably, the above "freeze drying" step is divided into two stages: (b-1) the freezing temperature is -70 ℃ to -90 ℃, for example: -75 ℃, -80 ℃ or -85 ℃; and (b-2) The freezing temperature is -2°C to -10°C, for example: -3°C, -4°C, -5°C, -6°C, -7°C, -8°C or -9°C.

Preferably, the above (b-1) freeze-drying time is 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 hours, more preferably 1 to 4 hours; the above (b-) 2) The freeze-drying time is 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 hours.

The purpose of this new type of freeze-drying technology is to use silk protein as a carrier to facilitate the preservation of other drugs or active ingredients in the silk protein, so that the drug or active ingredient is released in the body and the overall therapeutic time is prolonged; in addition, freeze-drying also has Helps stabilize the structure of the main layer.

More preferably, the method for preparing the main body layer may further include a heating and drying step: (b-3) The heating temperature is 15°C to 40°C, for example: 20°C, 25°C, 30°C or 35°C, and the heating and drying time is 0.5 , 1, 2, 3, 4, 5, 6, 7 or 8 hours.

In one embodiment, the freeze-drying step uses a manifold freeze-dryer.

The temperature of the condensing tank of the manifold freeze dryer is set below -40°C, for example: -40°C, -45°C, -50°C, -55°C or -60°C, and the freeze drying time is 4 to 24 hours.

In another embodiment, the freeze-drying step uses a shelf-type freeze dryer.

Preferably, the temperature of the condenser pipe of the shelf-type freeze dryer is set to -70°C to -90°C to control the temperature in the cavity of the shelf-type freeze dryer to reach the same temperature range. The shelf plate of the shelf-type freeze dryer The temperature is set at 20°C to 40°C, for example: 25°C, 30°C or 35°C, and the freeze-drying time is 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 hours, the interval formed by any two of its equivalent values, or any value within the interval formed by any of its two equivalent values.

Preferably, when the above-mentioned shelf-plate freeze dryer is used for the freeze drying step, the temperature in the cavity can be further brought back to -2°C to -8°C, and the freeze drying time is 0.5 to 10 hours.

More preferably, when the above-mentioned shelf-plate freeze dryer is used for the heating and drying step, the temperature in the chamber can be raised to 15°C to 40°C, and the heating and drying time is 0.5 to 5 hours.

In the novel anti-adhesive patch that can be degraded in vivo, the main body layer can also be prepared by the following steps: (a) The silk protein and the hydrophilic polymer material are uniformly mixed to form a silk protein hydrophilic polymer material mixed solution; and, (b) The mixed solution of the hydrophilic polymer material of silk protein is dried in two stages, namely, heat drying and vacuum drying at room temperature, and then the whole piece is removed to form the main body layer.

The new type adopts heating and drying technology to enhance the stability and configuration of the film, and within the temperature control range below 120 ℃, the silk protein will not be denatured, so that the finished product can produce a relatively flat and beautiful film.

Preferably, the baking temperature in the heating and drying step is lower than 120°C, more preferably 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110 , Any one of 115°C, the interval formed by any two of its equivalent values, or any value within the interval formed by any of its two equivalent values. Even better, the baking temperature is set to 55±1°C.

Preferably, the baking time of the heating and drying step is 0.5 to 10 hours, more preferably any one of 1, 2, 3, 4, 5, 6, 7, 8, 9 hours, and any other value The interval formed, or any value within the interval formed by any two of its equivalent values. Even better, the baking time is 1 to 6 hours.

Preferably, the heating and drying step uses an oven.

Preferably, the silk protein is an aqueous solution of silk protein; more preferably, the silk protein is an aqueous solution of silk protein added with ethanol; wherein, the addition of ethanol helps to shape the main layer, and the total amount of the aqueous solution of silk protein (containing ethanol) is Based on the weight, the ethanol content is 2 wt% to 6 wt%, preferably 3 wt% to 5 wt%, and more preferably 4 wt%. After drying, the ethanol will be substantially removed, and the anti-sticking patch (ie, the finished product) will have no residual detection value of ethanol.

In one embodiment, the body layer further uses a hydrophobic degradable polymer. The addition of a hydrophobic degradable polymer can increase the degradation time of the body layer in the body and provide a longer period of isolation.

Preferably, the hydrophobic degradable polymer is selected from poly(lactic acid), PLA, poly(ε-caprolactone), PCL, and polyglycolic acid (PGA) Any one or a combination of these.

More preferably, the molecular weight of the hydrophobic degradable polymer is between 10,000 Dalton and 250,000 Dalton. Even better, the molecular weight of the hydrophobic degradable polymer is between 20,000 Dalton and 160,000 Dalton.

Among them, the molecular weight of PLA is between 40,000 Dalton and 200,000 Dalton, more preferably 60,000 Dalton and 160,000 Dalton; the molecular weight of PCL is between 20,000 Dalton and 60,000 Dalton, the better is 40,000 Daltons to 50,000 Daltons; PGA molecular weights range from 15,000 Daltons to 160,000 Daltons, more preferably 20,000 Daltons to 145,000 Daltons.

Preparation Example 1: Silk protein extract

(1) Sterilization and degumming: Take 10 grams (g) of silkworm cocoons after removing impurities into a beaker containing 700 milliliters (ml) of purified water, and cover with aluminum foil. Place the beaker in an upright sterilizer and sterilize it at 121°C for 30 minutes. Clamp the degummed wire into a 20-liter (L) bucket with tweezers, wash it with purified water, and dry it. The degummed silk was added to a beaker containing 700 ml of purified water, and sterilized again at 121°C for 30 minutes for the second degumming, and the second degummed silk was obtained. After the second sterilization and washing, the second degummed silk (ie, silk protein) is dried for at least 18 hours and then stored in a moisture-proof box.

(2) Dissolve silk protein: dispose 9.3M lithium bromide aqueous solution with the total number of milliliters required in the ratio of 1g secondary degummed silk to 10 mL lithium bromide (LiBr) aqueous solution. After heating the 9.3M lithium bromide aqueous solution to 76 ± 2°C and 300 rpm with a heating stirrer for 5 minutes, secondary degummed silk is added. After about 5 to 20 minutes, the secondary degummed silk (ie, silk protein) is completely dissolved. After the lithium bromide aqueous solution was kept in a heated state and stirred uniformly for 60 minutes, a silk protein lithium bromide aqueous solution was prepared.

(3) Dialysis and recovery of silk protein extract: cut the dialysis bag on the cutting pad, take 1 L of secondary water in a 30 L bucket, put the dialysis bag in the bucket and soak for 5 minutes, then apply the above silk protein lithium bromide aqueous solution to The electric suction tube assistant is equipped with a 25 ml plastic suction tube and divided into dialysis bags. Two dialysis clips are clamped at each end and placed in a 30 L bucket. The dialysis is performed by an automatic water exchange system: the water is changed every 3 hours, and the total dialysis time 16 hours. After the dialysis is completed, the dialysate is centrifuged (2500 rpm/4°C/10 minutes), and the supernatant is taken to obtain the silk protein extract.

The silk protein extract obtained above is sent to the ultra-trace industrial safety laboratory for component analysis. The detection method of hydrolyzed amino acids is based on AOAC 994.12 Amino Acid in Feeds and analyzed by high-performance liquid chromatography; the protein is measured by a spectrophotometer (UV -VIS), the results are shown in Table 1.

Table 1: Composition of silk protein amino acids

From the ratio of amino acids shown in Table 1, it is known that the concentration of Glycine is the highest, reaching 16,700 ppm, followed by Alanine, with a concentration of 12,500 ppm, and then Serine and Tyrosine ( Tyrosine), its concentration is 5520ppm and 4670ppm. Since the concentration of amino acids contained in the silk protein extract is the top three named glycine, alanine, and serine, rather than serine, glycine, and aspartic acid, it is known that the silk protein extract used in this novel It is a water-soluble silk fibroin solution, that is, the main component is silk fibroin, and it does not contain sericin or has low sericin content.

In addition, further conversion from the concentration in Table 1 shows that the content of glycine should account for 36.17% of the total detection, alanine 27.08%, serine 11.96% and tyrosine 10.12%, and the concentration of cystine 24ppm below the minimum detection limit is not detected, and the content of methionine should account for 0.07% of the total detection, which is significantly less than 1% and less than 0.1%.

Embodiment 1: As can be seen from FIG. 1, the anti-sticking patch that can be degraded in vivo provided by this embodiment includes: a main body layer 10, which is a single-layer sheet body, and has a plurality of pores 20, and a length L, The width W and the height H can be adjusted according to requirements. In this embodiment, the patch area is square.

Embodiment 2: As can be seen from FIG. 2, the body-degradable anti-sticking patch provided in this embodiment is the same as that in Embodiment 1, and also includes: a body layer 10, which is a single-layer sheet body and has a length L , Width W and height H can be adjusted according to requirements, and the length L and width W of Example 2 are different from Example 1, the patch area is rectangular.

Embodiment 3: As can be seen from FIG. 3, the in vivo degradable anti-sticking patch provided in this embodiment includes two covering layers 30, which are respectively disposed on both sides of the main body layer 10 to form three layers structure. The length L, width W and height H of the body layer and the cover layer can be adjusted according to requirements, and the length L of the body layer 10 is the same size as the width W and the cover layer 30. In this embodiment, the patch area is square.

Embodiment 4: As can be seen from FIG. 4, the body-degradable anti-sticking patch provided in this embodiment is the same as that in Embodiment 3, and also includes two cover layers 30, which are respectively disposed on the main body layer 10 On both sides to form a three-layer structure. The length L, width W and height H of the body layer and the cover layer can be adjusted according to requirements, and the length L of the body layer is the same size as the width W and the cover layer, and the patch area is rectangular.

Example 5: Preparation of silk protein body layer

PVA (purchased from SIGMA ALDRICH, with an average molecular weight of 13,000 to 23,000 Daltons, a concentration of 98% and being hydrolyzed) was used to prepare a PVA aqueous solution with a concentration of 8 wt% using purified water. The above silk protein extract is diluted with purified water and ethanol to prepare an aqueous solution of silk protein, in which each group of aqueous solution of silk protein contains 3 wt% ethanol. The silk protein aqueous solution and the PVA aqueous solution are uniformly mixed to form a silk protein PVA mixed solution, and the formula is shown in Table 2.

In Groups A to F, the silk protein PVA mixture was poured into a circular mold with a diameter of 35 mm, and then freeze-dried in a manifold freeze dryer. The temperature of the condensing tank was set to -50°C or less and the vacuum was maintained for 14 hours. The silk protein main layer was prepared.

Group G is to pour the silk protein PVA mixture into a square mold with a length and width of 130*130 mm, and then freeze-dry using a shelf-plate type freeze dryer. The temperature of the shelf plate is set to 28°C, and the condenser is pre-cooled After -80 ℃ or less, vacuum is maintained for 2 hours, and then the temperature in the cavity of the shelf-type freeze dryer is increased to -5 ℃, and the main layer of silk protein is prepared after maintaining the vacuum for 1 hour.

Group H is also to pour the silk protein PVA mixture into a square mold with a length and width of 130*130 mm, and then freeze-dry using a shelf-plate freeze dryer, where the temperature of the shelf plate is set to 28°C, and the shelf plate is first frozen After the temperature in the dryer cavity is lowered to -30℃ for 5 hours, and then the condenser is pre-cooled to below -80℃, then vacuum is maintained for 3 hours, and then the temperature is increased in two stages: (1) Increase the temperature in the cavity to- Maintain the vacuum at 5°C for 6 hours, and (2) Raise the temperature in the chamber to +30°C and maintain the vacuum for 2 hours to prepare the main silk protein layer.

註：S為蠶絲蛋白水溶液，P為PVA水溶液，如蠶絲蛋白PVA混合液體積為30毫升且S:P為2:1者，表示蠶絲蛋白水溶液為20毫升：PVA水溶液為10毫升。 Table 2: Formula of silk protein PVA mixed solution:

Note: S is an aqueous solution of silk protein, and P is an aqueous solution of PVA. For example, if the volume of the mixed solution of silk protein PVA is 30 ml and S:P is 2:1, it means that the aqueous solution of silk protein is 20 ml: the aqueous solution of PVA is 10 ml.

As can be seen from Figures 5A to 5F, since the volume of the silk protein PVA mixture is 1 ml, the main layer is a thin film, and its transparency is not affected by the mixing ratio of the silk protein aqueous solution and the PVA aqueous solution or the change of the silk protein concentration. When the content of silk protein is increased to increase the body layer to promote wound healing and anti-inflammatory effects, the body layer can still remain transparent, which is convenient for surgical operations.

It can be seen from FIG. 5G that although the volume of the silk protein PVA mixed solution reaches 18 ml, the main layer is also a thin film due to the large mold area. After adjusting the parameters according to the characteristics of different freeze dryers, the main layer with the same transparency can be obtained.

It can be seen from Figure 5H that the volume of the silk protein PVA mixture is 36 ml, although it is only twice that of Group G, but due to the difference in drying conditions, it is not only opaque white, and from Figure 5I, the thickness has increased significantly and exceeded 2mm, and The main body layer is more fluffy and has obvious bubble film structure.

10: Main layer 20: Hole gap 30: Overlay W: width L: long degree H: High degree

FIG. 1 is a perspective view of an anti-adhesive patch degradable in vivo according to a first embodiment.

FIG. 2 is a perspective view of an anti-adhesive patch that can be degraded in vivo in the second embodiment.

FIG. 3 is a perspective view of an anti-adhesive patch degradable in vivo according to a third embodiment.

4 is a perspective view of an anti-adhesive patch degradable in vivo according to a fourth embodiment.

Figures 5A, 5B, 5C, 5D, 5E, 5F, 5G, 5H and 5I are the finished photos of the anti-adhesive patch that can be degraded in vivo.

10: Main layer

20: Pore

W: width

L: length

H: height

Claims (19)

An anti-sticking patch that promotes wound healing, anti-inflammatory and degradable in vivo, includes: a main body layer, the main body layer is a single-layer sheet body, and has a plurality of pores, wherein the main body layer includes silk protein and a hydrophilic polymer material And, the silk protein contains fibroin, and the hydrophilic polymer material is a biodegradable polymer with biocompatible properties. The anti-adhesive patch degradable in vivo as described in claim 1, wherein the body layer has a foam structure. The anti-adhesive patch which can be degraded in vivo as described in claim 1, wherein the main body layer is prepared by using freeze drying technology or casting technology. The anti-sticking patch which can be degraded in vivo as described in claim 3, wherein the main body layer is prepared without adding a crosslinking agent or using ultraviolet radiation. The anti-adhesive patch degradable in vivo according to claim 1, wherein the silk protein is selected from any one or a combination of water-soluble silk protein, silk protein powder ingot, and silk protein stock solution. The anti-adhesive patch degradable in vivo as described in claim 1, wherein the amino acid component of the silk protein contains at least: Alanine, Arginine, Aspartic acid , Glutamic acid, Glycine, Histidine, Isoleucine, Leucine, Lysine, Methionine ( Methionine, Phenylalanine, Proline, Serine, Threonine, Tyrosine, Valine, and Tryptophan , And based on the total weight of various amino acids detected by the silk protein, the content of Alanine is 25 to 30%, the content of Glycine is 33 to 39%, serine The content of Serine is 9 to 15% and/or the content of Tyrosine is 7 to 13%. The anti-adhesive patch which can be degraded in vivo as described in claim 6, wherein the cystine acid content of the silk protein is undetected and/or the methionine content is less than 1%. The anti-adhesive patch degradable in vivo as described in claim 6, wherein the content of thiamine acid in the silk protein is less than 1%. The in vivo degradable anti-sticking patch according to claim 1, wherein the biocompatible biodegradable polymer is selected from polyvinyl alcohol (PVA) and polyethylene glycol (polyethylene glycol) , PEG / polyethylene oxide, PEO, starch, collagen, gelatin, hyaluronic acid, polyvinylpyrrolidone (PVP), and carboxymethyl cellulose , CMC) or any combination thereof. The in vivo degradable anti-sticking patch according to claim 9, wherein the molecular weight of the biocompatible biodegradable polymer is between 10,000 and 400,000 Daltons. The in vivo degradable anti-sticking patch as described in claim 9, wherein the biocompatible biodegradable polymer is polyvinyl alcohol with a molecular weight of 12,000 to 74,800 daltons, and/or The degree of polymerization is 295 to 1700. The anti-adhesive patch degradable in vivo as described in claim 1, wherein the weight percentage of the silk protein is 60 to 90% based on the total weight of the two raw materials of the silk protein and the hydrophilic polymer material, and The weight percentage of the hydrophilic polymer material is 10 to 40%. The anti-adhesive patch degradable in vivo as described in claim 9, wherein the concentration of the raw materials is: the concentration of the silk protein is 50 to 120 mg/ml or the concentration by weight is 5 to 12%, and when the hydrophilic When the polymer material is polyvinyl alcohol, the weight percent concentration of the polyvinyl alcohol is 5 to 10%; when the hydrophilic polymer material is polyethylene glycol (polyethylene glycol, PEG), the polyethylene glycol ( The weight percentage of polyethylene glycol (PEG) is 2 to 4.5%, or when the hydrophilic polymer material is polyethylene oxide (PEO), the weight of the polyethylene oxide (PEO) The percentage concentration is 0.15 to 1%. The anti-adhesive patch degradable in vivo as described in claim 1, wherein the main body layer is prepared by the following steps: (a) The silk protein and the hydrophilic polymer material are mixed uniformly to form a mixed solution of the silk protein hydrophilic polymer material; (b) freeze-drying the silk polymer hydrophilic polymer material mixture at a freezing temperature of -25°C or lower to form a frozen silk protein mixture; and, (c) After the frozen silk protein mixture is dried, the whole piece is stripped to form the main layer. The anti-adhesive patch degradable in vivo as described in claim 1, wherein the main body layer is prepared by the following steps: (a) The silk protein and the hydrophilic polymer material are uniformly mixed to form a silk protein hydrophilic polymer material mixed solution; and, (b) The mixed solution of the hydrophilic polymer material of silk protein is dried in two stages, namely, heat drying and vacuum drying at room temperature, and then the whole piece is removed to form the main body layer. The anti-adhesive patch degradable in vivo as described in claim 1, wherein the single-layer sheet is a transparent or translucent film. The anti-adhesive patch that can be degraded in vivo as described in claim 1, wherein the single-layer sheet has a length of 60 to 90 mm and/or a width of 60 to 90 mm and/or a thickness of 0.7 to 1.3 mm Centimeters. The anti-adhesive patch that can be degraded in vivo as described in claim 1, further includes two covering layers, which are respectively disposed on both sides of the main body layer to form a three-layer structure. The anti-adhesive patch degradable in vivo as described in claim 18, wherein the material of the covering layer is polyvinyl alcohol, polyethylene glycol (PEG/polyethylene oxide, PEO) or polyethylene (PE) .

Images