Preparation method of anti-adhesion surgical flushing fluid

Abstract

The invention relates to the technical field of medical instruments, in particular to a preparation method of anti-adhesion surgical flushing fluid, which is prepared from the following raw materials in parts by mass: 8 to 13 parts of modified carboxymethyl cellulose, 2.3 to 4 parts of modified hyaluronic acid, 4 to 7 parts of sodium chloride, 20 to 23 parts of disodium hydrogen phosphate, 4 to 4.6 parts of sodium dihydrogen phosphate and 1000 parts of water for injection. The anti-adhesion surgical flushing fluid is prepared by mixing and moist heat sterilization. Wherein the modified carboxymethyl cellulose is prepared from gamma-polyglutamic acid, carboxymethyl cellulose and liquid paraffin, has good biocompatibility and moisture retention, is beneficial to wound healing, covers irregular wounds and is fixed on target tissues to form a physical barrier to prevent adhesion; the modified hyaluronic acid has acid-removing, wetting and anti-inflammatory properties and also has certain degradation resistance, so that postoperative tissue adhesion is effectively prevented, and compared with the prior art, the modified hyaluronic acid has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a method for preparing an anti-adhesion surgical flushing solution. Background Art

[0002] Tissue adhesion is very likely to occur after surgery. Adhesion refers to the abnormal structure formed by the combination of connective tissue fiber bands and adjacent tissues or organs. This is a process that patients must go through during the postoperative healing process. If adhesion occurs during surgery on the abdominal or pelvic bones, it will cause serious complications, such as adhesive intestinal obstruction in the abdomen and pelvis, recurrent laryngeal nerve damage after thyroid surgery, and female infertility due to pelvic tissue adhesion.

[0003] There are many causes of tissue adhesion, such as trauma during surgery, inflammation caused by local ischemia, foreign bodies in the body, bacterial infection at bleeding sites or exposed wounds. For example, after normal tissues suffer various injuries and cause inflammatory exudates and bleeding, abnormal adhesions will occur in adjacent separated tissues, which will restrict the movement of the injured part or cause varying degrees of functional disorders. Surgical adhesions usually occur after surgical operations on the abdominal cavity, cardiovascular, spine, joints, tendons, etc. Adhesions will involve the intestines and the greater omentum, leading to many complications, such as intestinal obstruction, chronic abdominal pain, pelvic and abdominal adhesions, etc. Postoperative adhesions will not only affect the effect of the operation, leading to serious postoperative complications, but also lead to surgical failure, such as infertility in women. Therefore, surgical adhesions have always been a common and thorny problem in surgical operations.

[0004] In recent years, researchers have conducted a large number of experiments and clinical studies, and adopted a variety of methods and measures to prevent postoperative adhesion, such as improving surgical techniques, applying mechanical barriers or solution barriers to isolate the serosal surface, using fibrinolytic drugs or anticoagulants to interfere with fiber formation, and combining traditional Chinese and Western medicine to prevent adhesion, but the effects are not ideal and there are certain side effects. At present, commonly used surgical flushing fluids in clinical practice are such as mannitol flushing fluid, glycine flushing fluid and physiological saline flushing fluid. For example, patent technology document CN106176805A discloses a gynecological surgery anti-adhesion flushing fluid and a preparation method thereof, which is prepared from the following raw materials: icodextrin, sodium chloride, calcium chloride, magnesium chloride, sodium lactate, and injection water. The invention makes full use of the anti-adhesion effect of icodextrin, and adds calcium ions, magnesium ions and sodium lactate. The addition of calcium ions and magnesium ions enhances its antibacterial and antibacterial ability. Sodium lactate, as a pH buffer, ensures normal osmotic pressure and pH value in the abdominal cavity. The invention has a certain effect in cleaning the surgical site and improving the clarity of the surgical field, but the effect of preventing postoperative adhesion needs to be improved.

[0005] Therefore, according to the above-mentioned related technologies, it is urgent to develop a method for preparing an anti-adhesion surgical flushing solution. Summary of the invention

[0006] In view of this, the purpose of the present invention is to provide a method for preparing an anti-adhesion surgical flushing solution to solve the problem that the surgical flushing solution in the prior art has a poor anti-adhesion effect.

[0007] Based on the above purpose, the present invention provides a method for preparing an anti-adhesion surgical flushing solution.

[0008] A method for preparing an anti-adhesion surgical flushing solution, comprising the following raw materials in parts by weight:

[0009] 8-13 parts of modified carboxymethyl cellulose, 2.3-4 parts of modified hyaluronic acid, 4-7 parts of sodium chloride, 20-23 parts of disodium hydrogen phosphate, 4-4.6 parts of sodium dihydrogen phosphate, 1000 parts of water for injection;

[0010] The modified carboxymethyl cellulose is prepared from γ-polyglutamic acid, carboxymethyl cellulose and liquid paraffin;

[0011] The modified hyaluronic acid is prepared from hyaluronic acid and glyceraldehyde methacrylate.

[0012] Preferably, the preparation method of the modified carboxymethyl cellulose is as follows:

[0013] Step A1. Add carboxymethyl cellulose to a 0.5 mol / L sodium hydroxide aqueous solution and stir until completely dissolved to obtain a mixture A. Add γ-polyglutamic acid to N,N-dimethylformamide, stir evenly, and then add to the mixture A to obtain a mixture B.

[0014] Step A2. Add ethylene glycol diglycidyl ether to mixture B at a speed of 230-270 r / min, stir for 10-15 min, then add liquid paraffin at 50-60° C., stir at a speed of 280-350 r / min for 3-4 h to obtain mixture C;

[0015] Step A3. The mixture C is washed 2-3 times with a soda water solution, immersed in methanol until the pH value reaches 7.0, and dried under reduced pressure at 35-45° C. to obtain modified carboxymethyl cellulose.

[0016] Preferably, the usage ratio of the carboxymethyl cellulose and the sodium hydroxide aqueous solution in step A1 is 1-3 g:40-120 mL.

[0017] Preferably, the usage ratio of γ-polyglutamic acid, N,N-dimethylformamide and mixture A in step A1 is 0.3-0.5 g: 8-12 mL: 43-48 mL.

[0018] Preferably, the usage ratio of the mixture B, ethylene glycol diglycidyl ether and liquid paraffin in step A2 is 20-40 mL: 0.15-0.35 g: 100-200 mL.

[0019] Preferably, the mass fraction of the soda water solution in step A3 is 1%-2%.

[0020] Preferably, the preparation method of the modified hyaluronic acid is as follows:

[0021] Add hyaluronic acid to an acetone aqueous solution, stir evenly, add glyceraldehyde methacrylate and triethylamine, stir for 20-24 hours, precipitate with acetone, and then vacuum filter to obtain modified hyaluronic acid.

[0022] Preferably, the mass fraction of the acetone aqueous solution is 45%-50%.

[0023] Preferably, the dosage ratio of the hyaluronic acid, acetone aqueous solution, glyceraldehyde methacrylate, triethylamine and acetone is 0.2-0.3 g: 15-20 mL: 2.6-3 g: 4-6 g: 36-44 mL. Preferably, the method comprises the following steps:

[0024] Add modified carboxymethyl cellulose and modified hyaluronic acid into water for injection, stir evenly, then add sodium chloride, disodium hydrogen phosphate and sodium dihydrogen phosphate, oscillate ultrasonically for 20-22 hours, and sterilize by wet heat at 121°C for 10 minutes to obtain the anti-adhesion surgical flushing solution.

[0025] Beneficial effects of the present invention:

[0026] The invention provides a method for preparing an anti-adhesion surgical flushing liquid. The invention prepares a surgical flushing liquid with good anti-adhesion effect from modified carboxymethyl cellulose, modified hyaluronic acid, sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate and water for injection; wherein the modified carboxymethyl cellulose is prepared from gamma-polyglutamic acid, carboxymethyl cellulose and liquid paraffin, has good biocompatibility and moisture retention, is conducive to wound healing, covers irregular wounds and is fixed on target tissues to form a physical barrier to prevent adhesion; hyaluronic acid itself has wetting and anti-inflammatory properties, and the modified hyaluronic acid improves the anti-degradation property, so that the modified hyaluronic acid can maintain stability for a long time in the body, thereby effectively preventing the occurrence of postoperative tissue adhesion. Compared with the prior art, the modified hyaluronic acid has broad application prospects. DETAILED DESCRIPTION

[0027] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments.

[0028] The sources and properties of some of the raw materials used in the present invention are as follows:

[0029] Carboxymethyl cellulose was purchased from Anhui Shanhe Pharmaceutical Excipients Co., Ltd.; γ-polyglutamic acid was purchased from Beijing Baier Ruisen Biotechnology Co., Ltd.; ethylene glycol diglycidyl ether was purchased from Zhongshan Dixin Chemical Co., Ltd.; liquid paraffin was purchased from Taizhou Petrochemical Co., Ltd.; hyaluronic acid was purchased from Huaxi Biotechnology Co., Ltd.; glyceraldehyde methacrylate was purchased from Tianmen Hengchang Chemical Co., Ltd.; and triethylamine was purchased from Yihaida New Materials (Tianjin) Co., Ltd.

[0030] Embodiment 1: A method for preparing an anti-adhesion surgical flushing solution, comprising the following steps:

[0031] S1. 1 g of carboxymethyl cellulose was added to 40 mL of a 0.5 mol / L sodium hydroxide aqueous solution and stirred until completely dissolved to obtain a mixture A. 0.3 g of γ-polyglutamic acid was added to 8 mL of N,N-dimethylformamide, stirred evenly, and then added to 43 mL of the mixture A to obtain a mixture B.

[0032] S2. Add 0.15 g of ethylene glycol diglycidyl ether to 20 mL of mixture B at a speed of 230 r / min, stir for 10 min, add 100 mL of liquid paraffin at 50°C, and stir at a speed of 280 r / min for 3 h to obtain mixture C;

[0033] S3. The mixture C was washed twice with a 1% soda water solution by mass, immersed in methanol until the pH value reached 7.0, and dried under reduced pressure at 35° C. to obtain modified carboxymethyl cellulose;

[0034] S4. 0.2 g of hyaluronic acid was added to 15 mL of 45% acetone aqueous solution, stirred evenly, 2.6 g of glyceraldehyde methacrylate and 4 g of triethylamine were added, stirred for 20 h, precipitated with 36 mL of acetone, and vacuum filtered to obtain modified hyaluronic acid;

[0035] S5. Add 8g of modified carboxymethyl cellulose and 2.3g of modified hyaluronic acid into 1000mL of water for injection, stir evenly, then add 4g of sodium chloride, 20g of disodium hydrogen phosphate and 4g of sodium dihydrogen phosphate. After ultrasonic oscillation for 20h, sterilize with wet heat at 121℃ for 10min to obtain the anti-adhesion surgical flushing solution.

[0036] Embodiment 2: A method for preparing an anti-adhesion surgical flushing solution, comprising the following steps:

[0037] S1. 1.5 g of carboxymethyl cellulose was added to 60 mL of a 0.5 mol / L sodium hydroxide aqueous solution and stirred until completely dissolved to obtain a mixture A. 0.35 g of γ-polyglutamic acid was added to 9 mL of N,N-dimethylformamide, stirred evenly, and then added to 44 mL of the mixture A to obtain a mixture B.

[0038] S2. Add 0.20 g of ethylene glycol diglycidyl ether to 25 mL of mixture B at a speed of 240 r / min, stir for 13 min, then add 120 mL of liquid paraffin at 52° C., stir at a speed of 290 r / min for 3.5 h, and obtain mixture C;

[0039] S3. The mixture C was washed twice with a 1% soda water solution, immersed in methanol until the pH value reached 7.0, and dried under reduced pressure at 37° C. to obtain modified carboxymethyl cellulose;

[0040] S4. 0.22 g of hyaluronic acid was added to 17 mL of 45% acetone aqueous solution, stirred evenly, 2.65 g of glyceraldehyde methacrylate and 4.4 g of triethylamine were added, stirred for 21 h, precipitated with 38 mL of acetone, and vacuum filtered to obtain modified hyaluronic acid;

[0041] S5. Add 9g of modified carboxymethyl cellulose and 2.5g of modified hyaluronic acid into 1000mL of water for injection, stir evenly, then add 4.5g of sodium chloride, 20.5g of disodium hydrogen phosphate and 4.1g of sodium dihydrogen phosphate. After ultrasonic oscillation for 20.5h, sterilize with wet heat at 121℃ for 10min to obtain the anti-adhesion surgical flushing solution.

[0042] Embodiment 3: A method for preparing an anti-adhesion surgical flushing solution, comprising the following steps:

[0043] S1. 1.8 g of carboxymethyl cellulose was added to 80 mL of a 0.5 mol / L sodium hydroxide aqueous solution and stirred until completely dissolved to obtain a mixture A. 0.4 g of γ-polyglutamic acid was added to 10 mL of N,N-dimethylformamide, stirred evenly, and then added to 45 mL of the mixture A to obtain a mixture B.

[0044] S2. 0.24 g of ethylene glycol diglycidyl ether was added to 28 mL of mixture B at a speed of 250 r / min, and after stirring for 13 min, 140 mL of liquid paraffin was added at 55° C. and stirred at a speed of 300 r / min for 3.5 h to obtain mixture C;

[0045] S3. The mixture C was washed twice with a 1% soda water solution by mass, immersed in methanol until the pH value reached 7.0, and dried under reduced pressure at 35-45° C. to obtain modified carboxymethyl cellulose;

[0046] S4. 0.24 g of hyaluronic acid was added to 18 mL of 45% acetone aqueous solution, stirred evenly, 2.7 g of glyceraldehyde methacrylate and 4.8 g of triethylamine were added, stirred for 21 h, precipitated with 39 mL of acetone, and vacuum filtered to obtain modified hyaluronic acid;

[0047] S5. Add 11g of modified carboxymethyl cellulose and 2.8g of modified hyaluronic acid into 1000mL of water for injection, stir evenly, then add 5g of sodium chloride, 21g of disodium hydrogen phosphate and 4.2g of sodium dihydrogen phosphate. After ultrasonic oscillation for 21h, sterilize with wet heat at 121℃ for 10min to obtain the anti-adhesion surgical flushing solution.

[0048] Embodiment 4: A method for preparing an anti-adhesion surgical flushing solution, comprising the following steps:

[0049] S1. 2.1 g of carboxymethyl cellulose was added to 90 mL of a 0.5 mol / L sodium hydroxide aqueous solution and stirred until completely dissolved to obtain a mixture A. 0.43 g of γ-polyglutamic acid was added to 11 mL of N,N-dimethylformamide, stirred evenly, and then added to 46 mL of the mixture A to obtain a mixture B.

[0050] S2. 0.26 g of ethylene glycol diglycidyl ether was added to 32 mL of mixture B at a speed of 260 r / min, and after stirring for 13 min, 150 mL of liquid paraffin was added at 55° C. and stirred at a speed of 310 r / min for 3.5 h to obtain mixture C;

[0051] S3. The mixture C was washed three times with a 2% soda water solution, immersed in methanol until the pH value reached 7.0, and dried under reduced pressure at 42° C. to obtain modified carboxymethyl cellulose;

[0052] S4. 0.27 g of hyaluronic acid was added to 19 mL of 50% acetone aqueous solution, stirred evenly, 2.8 g of glyceraldehyde methacrylate and 5.5 g of triethylamine were added, stirred for 22 h, precipitated with 42 mL of acetone, and vacuum filtered to obtain modified hyaluronic acid;

[0053] S5. Add 12g of modified carboxymethyl cellulose and 3.3g of modified hyaluronic acid into 1000mL of water for injection, stir evenly, then add 5.8g of sodium chloride, 22g of disodium hydrogen phosphate and 4.3g of sodium dihydrogen phosphate. After ultrasonic oscillation for 21.5h, sterilize with wet heat at 121°C for 10min to obtain the anti-adhesion surgical flushing solution.

[0054] Embodiment 5: A method for preparing an anti-adhesion surgical flushing solution, comprising the following steps:

[0055] S1. 2.8 g of carboxymethyl cellulose was added to 100 mL of a 0.5 mol / L sodium hydroxide aqueous solution and stirred until completely dissolved to obtain a mixture A. 0.47 g of γ-polyglutamic acid was added to 12 mL of N,N-dimethylformamide, stirred evenly, and then added to 47 mL of the mixture A to obtain a mixture B.

[0056] S2. 0.32 g of ethylene glycol diglycidyl ether was added to 38 mL of mixture B at a speed of 260 r / min, and after stirring for 15 min, 180 mL of liquid paraffin was added at 60° C. and stirred at a speed of 330 r / min for 4 h to obtain mixture C;

[0057] S3. The mixture C was washed three times with a 2% soda water solution, immersed in methanol until the pH value reached 7.0, and dried under reduced pressure at 45° C. to obtain modified carboxymethyl cellulose;

[0058] S4. 0.28 g of hyaluronic acid was added to 20 mL of 50% acetone aqueous solution, stirred evenly, 2.9 g of glyceraldehyde methacrylate and 5.8 g of triethylamine were added, stirred for 23 h, precipitated with 44 mL of acetone, and vacuum filtered to obtain modified hyaluronic acid;

[0059] S5. Add 13g of modified carboxymethyl cellulose and 3.6g of modified hyaluronic acid into 1000mL of water for injection, stir evenly, then add 6.2g of sodium chloride, 23g of disodium hydrogen phosphate and 4.5g of sodium dihydrogen phosphate. After ultrasonic oscillation for 22h, sterilize with wet heat at 121°C for 10min to obtain the anti-adhesion surgical flushing solution.

[0060] Example 6: A method for preparing an anti-adhesion surgical flushing solution, comprising the following steps:

[0061] S1. 3 g of carboxymethyl cellulose was added to 120 mL of a 0.5 mol / L sodium hydroxide aqueous solution and stirred until completely dissolved to obtain a mixture A. 0.5 g of γ-polyglutamic acid was added to 12 mL of N,N-dimethylformamide and stirred evenly, and then added to 48 mL of the mixture A to obtain a mixture B.

[0062] S2. 0.35 g of ethylene glycol diglycidyl ether was added to 40 mL of mixture B at a speed of 270 r / min, and after stirring for 15 min, 200 mL of liquid paraffin was added at 60° C. and stirred at a speed of 350 r / min for 4 h to obtain mixture C;

[0063] S3. The mixture C was washed three times with a 2% soda water solution, immersed in methanol until the pH value reached 7.0, and dried under reduced pressure at 45° C. to obtain modified carboxymethyl cellulose;

[0064] S4. 0.3 g of hyaluronic acid was added to 20 mL of 50% acetone aqueous solution, stirred evenly, 3 g of glyceraldehyde methacrylate and 6 g of triethylamine were added, stirred for 24 h, precipitated with 44 mL of acetone, and vacuum filtered to obtain modified hyaluronic acid;

[0065] S5. Add 13g of modified carboxymethyl cellulose and 4g of modified hyaluronic acid into 1000mL of water for injection, stir evenly, then add 7g of sodium chloride, 23g of disodium hydrogen phosphate and 4.6g of sodium dihydrogen phosphate. After ultrasonic oscillation for 22h, sterilize with wet heat at 121°C for 10min to obtain the anti-adhesion surgical flushing solution.

[0066] Comparative Example 1:

[0067] Compared with Example 1, modified carboxymethyl cellulose was not added in the preparation process of the anti-adhesion surgical flushing solution in this comparative example, and the remaining steps and parameters were the same, which will not be repeated in this comparative example, and finally the anti-adhesion surgical flushing solution was obtained.

[0068] Comparative Example 2:

[0069] Compared with Example 1, the modified hyaluronic acid was not added in the preparation process of the anti-adhesion surgical flushing solution in this comparative example, and the remaining steps and parameters were the same, which will not be repeated in this comparative example, and finally the anti-adhesion surgical flushing solution was obtained.

[0070] Comparative Example 3:

[0071] Compared with Example 1, this comparative example only replaces "modified carboxymethyl cellulose" with "carboxymethyl cellulose", and the remaining steps and parameters are the same, which will not be repeated in this comparative example, and finally an anti-adhesion surgical flushing solution is obtained.

[0072] Comparative Example 4:

[0073] Compared with Example 1, this comparative example only replaces "modified hyaluronic acid" with "hyaluronic acid", and the remaining steps and parameters are the same, which will not be repeated in this comparative example, and finally an anti-adhesion surgical flushing solution is obtained.

[0074] Comparative Example 5:

[0075] Compared with Example 1, this comparative example does not add γ-polyglutamic acid during the preparation of modified carboxymethyl cellulose, and the remaining steps and parameters are the same, which will not be repeated in this comparative example. Finally, an anti-adhesion surgical flushing solution is obtained.

[0076] Performance Testing:

[0077] A total of 220 male SD rats were randomly divided into 11 groups with 20 rats in each group. The postoperative abdominal adhesion model was established by the rasp method: the animals were fasted for 12 hours, anesthetized with 10% chloral hydrate, and a 1.5 cm anterior midline incision was made into the abdomen under aseptic operation after hair clipping and disinfection. The serous layer was repeatedly rubbed with an assorted rasp on the right side of the ileocecal region until a pinpoint bleeding point was formed on the surface, and a 4 cm 2 After the wound was damaged, it was exposed to air for 5 min before being placed into the abdominal cavity, and the abdominal cavity was closed layer by layer;

[0078] The rats in group A were the drug-treated group. Before the abdominal cavity was closed after the operation, the wound surface was irrigated with 10 ml of the irrigating solution prepared in Example 1. The rats in group B were the drug-treated group. Before the abdominal cavity was closed after the operation, the wound surface was irrigated with 10 ml of the irrigating solution prepared in Example 2. The rats in group C were the drug-treated group. Before the abdominal cavity was closed after the operation, the wound surface was irrigated with 10 ml of the irrigating solution prepared in Example 3. The rats in group D were the drug-treated group. Before the abdominal cavity was closed after the operation, the wound surface was irrigated with 10 ml of the irrigating solution prepared in Example 4. The rats in group E were the drug-treated group. Before the abdominal cavity was closed after the operation, the wound surface was irrigated with 10 ml of the irrigating solution prepared in Example 5. The rats in group F were the drug-treated group. Before the abdominal cavity was closed after the operation, The wound surface was rinsed with 10 ml of the rinsing solution prepared in Example 6; the rats in Group G were used as the control group, and the wound surface was rinsed with 10 ml of the rinsing solution prepared in Comparative Example 1 before the abdominal cavity was closed after the operation; the rats in Group H were used as the control group, and the wound surface was rinsed with 10 ml of the rinsing solution prepared in Comparative Example 2 before the abdominal cavity was closed after the operation; the rats in Group I were used as the control group, and the wound surface was rinsed with 10 ml of the rinsing solution prepared in Comparative Example 3 before the abdominal cavity was closed after the operation; the rats in Group J were used as the control group, and the wound surface was rinsed with 10 ml of the rinsing solution prepared in Comparative Example 4 before the abdominal cavity was closed after the operation; the rats in Group K were used as the control group, and the wound surface was rinsed with 10 ml of the rinsing solution prepared in Comparative Example 5 before the abdominal cavity was closed after the operation;

[0079] On the 14th day after surgery, the animals were killed by cervical dislocation and the abdomen was entered through a subxiphoid incision. A person who did not participate in the operation recorded the grading of each group of mice according to the Phillips grading standard and observed the adhesion conditions.

[0080] The Phillips grading standard is as follows: Grade 0: no adhesion at all, and the cecal serosal surface is well repaired; Grade I: a small amount of adhesion between the cecum and surrounding tissues, which is loose and easy to separate, and there is no bleeding; Grade II: mild to moderate adhesion between the cecum and surrounding tissues, the intestinal tract may be "U" shaped, and there is local bleeding when separated; Grade III: the intestinal tract is extensively adhered to the surrounding tissues, which is difficult to separate, and there is no intestinal obstruction; Grade IV: the intestinal tract is tightly adhered to the surrounding tissues, forming a mass, which is difficult to separate, causing incomplete or complete intestinal obstruction.

[0081] Table 1

[0082]

[0083]

[0084] Data Analysis:

[0085] As can be seen from Table 1, the anti-adhesion surgical flushing solution prepared by the present invention has a better anti-adhesion effect. This may be because the modified carboxymethyl cellulose has good water absorption performance on the one hand, can absorb a large amount of tissue exudate, is conducive to wound healing, covers irregular wounds and is fixed on the target tissue, forms a physical barrier to prevent adhesion and is degradable in the body, and the polysaccharides formed during its degradation process can also promote tissue healing; on the other hand, the γ-polyglutamic acid contained therein has antibacterial and hemostatic functions, can inhibit the growth of bacteria on the wound surface, and also has a certain moisturizing property, which can further enhance the moisturizing effect of the flushing solution; hyaluronic acid itself has wetting and anti-inflammatory properties, and the modified hyaluronic acid improves the anti-degradation property, so that it can maintain stability for a long time in the body, thereby effectively preventing the occurrence of postoperative tissue adhesion, and the synergistic compounding of modified carboxymethyl cellulose and modified hyaluronic acid makes the flushing solution have good anti-adhesion properties.

[0086] Those skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of the present invention is limited to these examples. Under the concept of the present invention, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of the different aspects of the present invention as described above, which are not provided in detail for the sake of simplicity.

[0087] The present invention is intended to cover all such substitutions, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing an anti-adhesion surgical flushing solution, characterized in that: Including the following raw materials by weight: 8-13 parts of modified carboxymethyl cellulose, 2.3-4 parts of modified hyaluronic acid, 4-7 parts of sodium chloride, 20-23 parts of disodium hydrogen phosphate, 4-4.6 parts of sodium dihydrogen phosphate, 1000 parts of water for injection; The modified carboxymethyl cellulose is prepared from γ-polyglutamic acid, carboxymethyl cellulose and liquid paraffin; The modified hyaluronic acid is prepared from hyaluronic acid and glyceraldehyde methacrylate.

2. The method for preparing an anti-adhesion surgical flushing solution according to claim 1, characterized in that: The preparation method of the modified carboxymethyl cellulose is as follows: Step A1. Add carboxymethyl cellulose to a 0.5 mol / L sodium hydroxide aqueous solution and stir until completely dissolved to obtain a mixture A. Add γ-polyglutamic acid to N,N-dimethylformamide, stir evenly, and then add to the mixture A to obtain a mixture B. Step A2. Add ethylene glycol diglycidyl ether to mixture B at a speed of 230-270 r / min, stir for 10-15 min, then add liquid paraffin at 50-60° C., stir at a speed of 280-350 r / min for 3-4 h to obtain mixture C; Step A3. The mixture C is washed 2-3 times with a soda water solution, immersed in methanol until the pH value reaches 7.0, and dried under reduced pressure at 35-45° C. to obtain modified carboxymethyl cellulose.

3. The method for preparing the anti-adhesion surgical flushing solution according to claim 2, characterized in that: The usage ratio of carboxymethyl cellulose and sodium hydroxide aqueous solution in step A1 is 1-3 g:40-120 mL.

4. The method for preparing the anti-adhesion surgical flushing solution according to claim 2, characterized in that: The usage ratio of γ-polyglutamic acid, N,N-dimethylformamide and mixture A in step A1 is 0.3-0.5 g: 8-12 mL: 43-48 mL.

5. The method for preparing the anti-adhesion surgical flushing solution according to claim 2, characterized in that: The usage ratio of the mixture B, ethylene glycol diglycidyl ether and liquid paraffin in step A2 is 20-40 mL: 0.15-0.35 g: 100-200 mL.

6. The method for preparing the anti-adhesion surgical flushing solution according to claim 2, characterized in that: The mass fraction of the soda water solution in step A3 is 1%-2%.

7. The method for preparing an anti-adhesion surgical flushing solution according to claim 1, characterized in that: The preparation method of the modified hyaluronic acid is as follows: Add hyaluronic acid to an acetone aqueous solution, stir evenly, add glyceraldehyde methacrylate and triethylamine, stir for 20-24 hours, precipitate with acetone, and then vacuum filter to obtain modified hyaluronic acid.

8. The method for preparing an anti-adhesion surgical flushing solution according to claim 7, characterized in that: The mass fraction of the acetone aqueous solution is 45%-50%.

9. The method for preparing an anti-adhesion surgical flushing solution according to claim 7, characterized in that: The dosage ratio of the hyaluronic acid, acetone aqueous solution, glyceraldehyde methacrylate, triethylamine and acetone is 0.2-0.3 g: 15-20 mL: 2.6-3 g: 4-6 g: 36-44 mL.

10. The method for preparing an anti-adhesion surgical flushing solution according to claim 1, characterized in that: The following steps are involved: Add modified carboxymethyl cellulose and modified hyaluronic acid into water for injection, stir evenly, then add sodium chloride, disodium hydrogen phosphate and sodium dihydrogen phosphate, oscillate ultrasonically for 20-22 hours, and sterilize by wet heat at 121°C for 10 minutes to obtain the anti-adhesion surgical flushing solution.

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