Special gel for medical surgical site ice compress and preparation method thereof

Abstract

The invention provides special gel for medical surgical site ice compress and a preparation method thereof, and relates to the technical field of medical treatment. The preparation raw materials at least comprise: a main polymer: polyvinyl alcohol (PVA), bacterial nanocellulose (BNC), and poly N-isopropylacrylamide; the functional additives comprise double modified starch (OSA + phosphate), nano-silver (the particle size is 20-50 nm), a thrombin-fibrinogen compound and EGF / bFGF microspheres (PLGA); and the auxiliary components comprise glycerol, citric acid and purified water. According to the multifunctional ice compress gel, a structure which is loose outside and tight inside is formed through freeze drying, the cold compress uniformity and the air circulation performance are improved, the double modified starch and the cross-linking agent cooperate, the degradation period is prolonged to 72 h, the replacement frequency is reduced, the multifunctional ice compress gel has the functions of physical cooling, hemostasis repair, antisepsis and anti-inflammation, the cooperative requirement of postoperative cold compress and wound surface nursing is met, and the multifunctional ice compress gel is worthy of popularization and application. The device is suitable for postoperative incision cold compress, burn / acute stage cooling and hemostasis of wounds and auxiliary repair of chronic wounds.

Description

TECHNICAL FIELD

[0001] The present application relates to the medical field, in particular to a medical operation site ice compress special gel and a preparation method thereof. BACKGROUND

[0002] The hydrogel is a gel with water as a dispersion medium, has strong hydrophilicity, and can be cross-linked to form a three-dimensional network structure through physical or chemical action. The hydrogel has some excellent properties that common polymer materials do not have, can help stimulate the patient's bone marrow to produce stem cells, promote cartilage regeneration, and can also be used as a lubricant in joints to reduce joint inflammation, so it has a very good application prospect in the medical field. The hydrogel will not cause friction to tissues or cells after absorbing water, and will not cause any discomfort to the human body when actually applied to postoperative wound repair. The hydrogel used in the medical field is generally referred to as a medical gel. The medical gel can replace the traditional medical suturing operation to better repair the damaged organs or tissues, effectively improve the efficiency of the operation, accelerate wound healing, and significantly reduce pain, providing more choices for doctors and patients.

[0003] At present, the traditional postoperative cold compress means (such as ice bag, cold compress towel) has problems of unstable temperature, easy to cause frostbite, poor fit, etc., and lacks bioactive ingredients, which cannot synergistically promote wound healing. The existing medical gel is mainly based on cyanoacrylate polymer, which can quickly stop bleeding, but lacks cold compress function and antibacterial repair performance.

[0004] Therefore, in view of the above problems, the present application provides a medical operation site ice compress special gel and a preparation method thereof, so as to achieve a more practical value. SUMMARY

[0005] (I) Technical problems solved

[0006] In view of the deficiencies of the prior art, the present application provides a medical operation site ice compress special gel and a preparation method thereof, develops a multifunctional ice compress gel with physical cooling, hemostatic repair and antibacterial anti-inflammatory functions, solves the synergistic needs of postoperative cold compress and wound care, and solves the problems mentioned in the above background.

[0007] (II) Technical solutions

[0008] To achieve the above purpose, the present application is realized by the following technical solutions: a medical operation site ice compress special gel, the preparation raw materials at least include:

[0009] Main polymer: polyvinyl alcohol (PVA), bacterial nanocellulose (BNC), poly-N-isopropyl acrylamide;

[0010] Functional additives: double modified starch (OSA + phosphate ester), nano-silver (particle size 20-50 nm), thrombin-fibrinogen complex, EGF / bFGF microspheres (PLGA);

[0011] Auxiliary ingredients, glycerol, citric acid, purified water.

[0012] As a kind of medical operation site ice special gel of the present application preferably, the preparation raw material at least includes according to mass fraction: 6-8 portions of polyvinyl alcohol (PVA), 1-2 portions of bacterial nanocellulose (BNC), 1-3 portions of poly-N-isopropyl acrylamide, 3-5 portions of double modified starch (OSA+phosphate ester), 0.02-0.05 portions of nano-silver (particle size 20-50 nm), 0.3-0.5 portions of thrombin-fibrinogen complex, 0.05-0.1 portions of EGF / bFGF microspheres (PLGA), 0.5-1 portions of glycerol, 0.3-0.5 portions of citric acid, 60-80 portions of purified water.

[0013] As a kind of medical operation site ice special gel of the present application preferably, the preparation method of the main polymer at least includes the following steps:

[0014] S1: PVA solution preparation: PVA is added to 80 ℃ purified water, mechanical stirring 2h to completely dissolve, cooling to 40 ℃;

[0015] S2: BNC dispersion: bacterial nanocellulose (dry weight) is added to PVA solution, high-speed homogenization (10000 rpm, 10 min) to form a uniform suspension;

[0016] S3: temperature-sensitive polymer introduction: PNIPAAm monomer (3 parts) and crosslinking agent (N,N'-methylene bisacrylamide, 0.1 parts) are added to the suspension, deoxygenated by nitrogen for 10 min, then light initiator (benzophenone, 0.05 parts) is added, and polymerization is initiated by ultraviolet light (365 nm, 15 min) to form a PVA / BNC / PNIPAAm interpenetrating network.

[0017] As a kind of medical operation site ice special gel of the present application preferably, the preparation method of the double modified starch at least includes the following steps:

[0018] S1: starch (5 parts) is reacted with succinic anhydride (1 part) at pH 8.5 for 4h to introduce carboxyl groups;

[0019] S2: add octenyl succinic anhydride (OSA, 0.5 parts), continue to react for 2h to form double modified starch;

[0020] S3: add sodium trimetaphosphate (0.2 parts), crosslink at 60 ℃ for 30 min to improve water resistance.

[0021] As a kind of medical operation site ice pack special gel of the application is preferably, the nano silver is loaded: the bimodified starch is suspended in silver nitrate solution (0.1 mol / L), and is reduced for 10 min under ultraviolet light, so that nano silver is uniformly loaded on the surface of starch.

[0022] As a kind of medical operation site ice pack special gel of the application is preferably, the thrombin-fibrinogen complex: thrombin (500IU) is dissolved in phosphate buffer with fibrinogen (50mg), and is prepared into microspheres by spray drying, and is mixed with starch.

[0023] As a kind of medical operation site ice pack special gel of the application is preferably, the growth factor microsphere preparation: EGF (10 μg) is encapsulated in PLGA microsphere (particle size 10-20 μm) with bFGF (10 μg) by double emulsion method (W / O / W), and is mixed with starch.

[0024] A kind of medical operation site ice pack special gel preparation method, comprising the following steps:

[0025] S1: mixing, functional additive (starch complex, thrombin microsphere, growth factor microsphere) is added to the main polymer solution, and is mechanically stirred for 30 min to be uniform;

[0026] S2: vacuum degassing, the mixed solution is placed in vacuum box (-0.08MPa, 15min) to remove air bubbles;

[0027] S3: low-temperature forming, injection silicone mold, -20 ℃ pre-freezing 2h, transfer to freeze dryer (-80 ℃, 10Pa, 12h) to form porous structure (pore size 50-100 μm);

[0028] S4: sterilization packaging, using gamma ray irradiation (25kGy) sterilization, operation cold compress gel is obtained, and is sealed in aluminum foil bag.

[0029] (Three) beneficial effects

[0030] The application provides a kind of medical operation site ice pack special gel and preparation method thereof.There is beneficial effect as follows:

[0031] In the present application, the automatic detachment of "cold fixation-removal liquefaction" is realized by the PNIPAAm temperature-sensitive polymer, avoiding the traditional gel adhesion to the wound, integrating the nanosilver antibacterial, thrombin hemostasis, growth factor repair, covering the whole cycle of postoperative care, freeze-drying to form a "loose inside and tight outside" structure, improving the uniformity of cold compress and air permeability, and the degradation period is extended to 72h by the synergistic effect of double modified starch and crosslinking agent, reducing the replacement frequency, a multifunctional ice compress gel with physical cooling, hemostasis repair and antibacterial and anti-inflammatory functions, which solves the synergistic demand of postoperative cold compress and wound care, and is suitable for postoperative incision cold compress (such as orthopedics and general surgery), burn / wound acute stage cooling and hemostasis, and auxiliary repair of chronic wounds (such as diabetic foot). DETAILED DESCRIPTION

[0032] The present application will be further described in detail by the following examples.

[0033] Example 1

[0034] The present application provides a medical gel for ice compress of surgical site, and the preparation raw materials at least include:

[0035] Main polymer: polyvinyl alcohol (PVA), bacterial nanocellulose (BNC), poly-N-isopropyl acrylamide;

[0036] Functional additives: double modified starch (OSA+phosphate), nanosilver (particle size 20-50nm), thrombin-fibrinogen complex, EGF / bFGF microspheres (PLGA);

[0037] Auxiliary ingredients, glycerol, citric acid, purified water.

[0038] The preparation raw materials at least include: 6 parts of polyvinyl alcohol (PVA), 1 part of bacterial nanocellulose (BNC), 1 part of poly-N-isopropyl acrylamide, 3 parts of double modified starch (OSA+phosphate), 0.02 parts of nanosilver (particle size 20-50nm), 0.3 parts of thrombin-fibrinogen complex, 0.05 parts of EGF / bFGF microspheres (PLGA), 0.5 parts of glycerol, 0.3 parts of citric acid, and 60 parts of purified water.

[0039] The preparation method of the main polymer at least includes the following steps:

[0040] S1: PVA solution preparation: add PVA into 80℃ purified water, mechanically stir for 2h until completely dissolved, and cool to 40℃;

[0041] S2: BNC dispersion: add bacterial nanocellulose (dry weight) into the PVA solution, high-speed homogenization (10000rpm, 10min) to form a uniform suspension;

[0042] S3: Temperature-sensitive polymer introduction: PNIPAAm monomer (3 parts) and crosslinking agent (N, N'-methylene bisacrylamide, 0.1 part) were added to the suspension, and after deoxygenation for 10 min under nitrogen, a photoinitiator (benzophenone, 0.05 parts) was added. Polymerization was initiated by ultraviolet light (365 nm, 15 min) to form a PVA / BNC / PNIPAAm interpenetrating network.

[0043] The method for preparing the double-modified starch comprises at least the following steps:

[0044] S1: Carboxyl group introduction: starch (5 parts) was reacted with succinic anhydride (1 part) at pH 8.5 for 4 h;

[0045] S2: Double-modified starch formation: octenyl succinic anhydride (OSA, 0.5 parts) was added, and the reaction was continued for 2 h;

[0046] S3: Water resistance improvement: sodium trimetaphosphate (0.2 parts) was added, and crosslinking was performed at 60°C for 30 min.

[0047] The nano-silver loading: the double-modified starch was suspended in a silver nitrate solution (0.1 mol / L), and ultraviolet light reduction was performed for 10 min to uniformly load nano-silver on the surface of the starch.

[0048] The thrombin-fibrinogen complex: thrombin (500 IU) and fibrinogen (50 mg) were dissolved in a phosphate buffer, spray-dried to form microspheres, and mixed with the starch.

[0049] The growth factor microsphere preparation: EGF (10 μg) and bFGF (10 μg) were encapsulated in PLGA microspheres (particle size 10-20 μm) by a double-emulsion method (W / O / W), and mixed with the starch.

[0050] A method for preparing a medical cold compress gel for a surgical site, comprising the following steps:

[0051] S1: Mixing: functional additives (starch complex, thrombin microspheres, growth factor microspheres) were added to the main polymer solution, and mechanical stirring was performed for 30 min until uniform;

[0052] S2: Vacuum degassing: the mixed solution was placed in a vacuum box (-0.08 MPa, 15 min) to remove air bubbles;

[0053] S3: Low-temperature molding: the silicone mold was injected, pre-frozen at -20°C for 2 h, transferred to a freeze dryer (-80°C, 10 Pa, 12 h) to form a porous structure (pore size 50-100 μm);

[0054] S4: Sterilization and packaging: γ-ray irradiation (25 kGy) was used for sterilization, and the surgical cold compress gel was obtained, which was sealed in an aluminum foil bag.

[0055] Embodiment 2

[0056] The embodiment of the present application provides a medical operation site ice compress special gel, and preparation raw materials at least include:

[0057] Main polymer: polyvinyl alcohol (PVA), bacterial nanocellulose (BNC), poly N-isopropyl acrylamide;

[0058] Functional additives: double modified starch (OSA+phosphate), nano silver (particle size 20-50nm), thrombin-fibrinogen complex, EGF / bFGF microspheres (PLGA);

[0059] Auxiliary ingredients, glycerol, citric acid, purified water.

[0060] Preparation raw materials at least include: 8 parts of polyvinyl alcohol (PVA), 2 parts of bacterial nanocellulose (BNC), 3 parts of poly N-isopropyl acrylamide, 5 parts of double modified starch (OSA+phosphate), 0.05 parts of nano silver (particle size 20-50nm), 0.5 parts of thrombin-fibrinogen complex, 0.1 parts of EGF / bFGF microspheres (PLGA), 1 parts of glycerol, 0.5 parts of citric acid, 80 parts of purified water.

[0061] The preparation method of the main polymer at least includes the following steps:

[0062] S1: PVA solution preparation: PVA is added to 80 DEG C purified water, and mechanically stirred for 2h to completely dissolve, and then cooled to 40 DEG C;

[0063] S2: BNC dispersion: bacterial nanocellulose (dry weight) is added to the PVA solution, and high-speed homogenization (10000rpm, 10min) is formed into a uniform suspension;

[0064] S3: Warm sensitive polymer introduction: PNIPAAm monomer (3 parts) and crosslinking agent (N,N'-methylene bisacrylamide, 0.1 parts) are added to the suspension, deoxygenated for 10min, then light initiator (benzophenone, 0.05 parts) is added, and polymerization is initiated by ultraviolet light (365nm, 15min) to form PVA / BNC / PNIPAAm interpenetrating network.

[0065] The preparation method of the double modified starch at least includes the following steps:

[0066] S1: starch (5 parts) is reacted with succinic anhydride (1 part) under the condition of pH 8.5 for 4h to introduce carboxyl;

[0067] S2: octenyl succinic anhydride (OSA, 0.5 parts) is added, and the reaction is continued for 2h to form double modified starch;

[0068] S3: Add sodium trimetaphosphate (0.2 parts), crosslink at 60°C for 30 min to improve water resistance.

[0069] The nano-silver is loaded by suspending the double-modified starch in a silver nitrate solution (0.1 mol / L) and reducing it under ultraviolet light for 10 min to make the nano-silver uniformly loaded on the surface of the starch.

[0070] The thrombin-fibrinogen complex is prepared by dissolving thrombin (500 IU) and fibrinogen (50 mg) in a phosphate buffer and spray-drying to form microspheres, which are then mixed with the starch.

[0071] The growth factor microspheres are prepared by encapsulating EGF (10 μg) and bFGF (10 μg) in PLGA microspheres (particle size 10-20 μm) by double-emulsion (W / O / W) method, which are then mixed with the starch.

[0072] A preparation method of a medical cold compress gel for surgical sites, comprising the following steps:

[0073] S1: Mixing, functional additives (starch complex, thrombin microspheres, growth factor microspheres) are added to the main polymer solution and mechanically stirred for 30 min until uniform;

[0074] S2: Vacuum degassing, the mixed solution is placed in a vacuum box (-0.08 MPa, 15 min) to remove air bubbles;

[0075] S3: Low-temperature molding, the silicone gel mold is injected, pre-frozen at -20°C for 2 h, transferred to a freeze dryer (-80°C, 10 Pa, 12 h) to form a porous structure (pore size 50-100 μm);

[0076] S4: Sterilization and packaging, sterilized by γ-ray irradiation (25 kGy) to obtain a cold compress gel for surgery, sealed in an aluminum foil bag.

[0077] Notes: Pregnant women, lactating women and people with allergic constitution should be cautious; avoid direct contact with open wounds, and use under sterile conditions; store in a 2-8°C environment, with a shelf life of 12 months.

[0078] Performance verification is shown in Table 1

[0079] Table 1

[0080]

[0081] Through the verification of Example 2 in actual application, the clinical performance, convenience and safety of the cold compress gel are significantly improved, providing an efficient and safe solution for postoperative care, which has broad prospects for industrialization.

[0082] While embodiments of the application have been shown and described, it is to be understood that the embodiments described are merely exemplary of the principles and application of the present application. Numerous modifications and adaptions can be effected without departing from the spirit and scope of the present application, which is not limited to the exact construction and arrangement described. It is intended, therefore, to cover all modifications and adaptions that fall within the scope of the claims and their equivalents.

Claims

1. A medical gel for surgical site dressing, characterized in that: the preparation raw materials at least include: the main polymer: polyvinyl alcohol (PVA), bacterial nanocellulose (BNC), poly-N-isopropyl acrylamide; functional additives: double modified starch (OSA + phosphate ester), nano-silver (particle size 20-50 nm), thrombin-fibrinogen complex, EGF / bFGF microspheres (PLGA); auxiliary ingredients, glycerol, citric acid, purified water.

2. A medical gel for ice pack on surgical site according to claim 1, characterized in that: The preparation raw materials at least include: 6-8 parts of polyvinyl alcohol (PVA), 1-2 parts of bacterial nanocellulose (BNC), 1-3 parts of poly-N-isopropyl acrylamide, 3-5 parts of double modified starch (OSA + phosphate ester), 0.02-0.05 parts of nano-silver (particle size 20-50 nm), 0.3-0.5 parts of thrombin-fibrinogen complex, 0.05-0.1 parts of EGF / bFGF microspheres (PLGA), 0.5-1 parts of glycerol, 0.3-0.5 parts of citric acid, 60-80 parts of purified water.

3. A medical gel for ice pack application to surgical sites as claimed in claim 1, wherein: The preparation method of the main polymer at least includes the following steps: S1: PVA solution preparation: add PVA to 80℃ purified water, mechanically stir for 2h until completely dissolved, cool to 40℃; S2: BNC dispersion: add bacterial nanocellulose (dry weight) to the PVA solution, high-speed homogenization (10000rpm, 10min) to form a uniform suspension; S3: Temperature-sensitive polymer introduction: add PNIPAAm monomer (3 parts) and crosslinking agent (N,N'-methylene bisacrylamide, 0.1 part) to the suspension, deoxidize for 10min under nitrogen, then add a photoinitiator (benzophenone, 0.05 part), initiate polymerization under ultraviolet light (365nm, 15min) to form a PVA / BNC / PNIPAAm interpenetrating network.

4. A medical gel for ice pack application to surgical sites as claimed in claim 1, wherein: The preparation method of the double modified starch at least includes the following steps: S1: starch (5 parts) and succinic anhydride (1 part) are reacted at pH 8.5 for 4h to introduce carboxyl groups; S2: add octenyl succinic anhydride (OSA, 0.5 parts), continue to react for 2h to form double modified starch; S3: add sodium trimetaphosphate (0.2 parts), crosslink at 60℃ for 30min to improve water resistance.

5. A medical gel for ice pack application to a surgical site according to claim 1, wherein: The nano-silver is loaded: suspend the double modified starch in a silver nitrate solution (0.1mol / L), reduce under ultraviolet light for 10min to uniformly load nano-silver on the surface of the starch.

6. A medical gel for ice packs for surgical sites according to claim 1, characterized in that: The thrombin-fibrinogen complex: dissolve thrombin (500IU) and fibrinogen (50mg) in phosphate buffer, spray dry to prepare microspheres, and mix with starch.

7. A medical gel for use in cold compresses for surgical sites according to claim 1, characterized in that: The growth factor microspheres are prepared: EGF (10μg) and bFGF (10μg) are encapsulated in PLGA microspheres (particle size 10-20μm) by double emulsion method (W / O / W), and mixed with starch.

8. A process for the preparation of a medical gel for ice packs for surgical sites according to any one of claims 1 to 7, characterized in that: The preparation method includes the following steps: S1: mixing, adding functional additives (starch complex, thrombin microspheres, growth factor microspheres) to the main polymer solution, mechanically stirring for 30min until uniform; S2: vacuum defoaming, the mixed solution was placed in a vacuum box (-0.08 MPa, 15 min) to remove bubbles; S3: low temperature molding, injecting the silica gel mold, pre-freezing at -20℃ for 2h, transferring to a freeze dryer (-80℃, 10 Pa, 12h) to form a porous structure (pore size 50-100μm); S4: sterilization packaging, using γ-ray irradiation (25kGy) sterilization, the surgical cold compress gel was obtained, sealed in an aluminum foil bag.

Images