Preparation method of sodium hyaluronate dressing with low bacterial endotoxin

Abstract

The invention discloses a preparation method of a sodium hyaluronate dressing with low bacterial endotoxin, which is characterized in that a bacterial endotoxin structure carried by a non-woven fabric material is destroyed at a raw material end in an alkali liquor soaking manner, and the bacterial endotoxin structure is further removed in a cleaning manner. Besides, in order to inhibit the growth of microorganisms in the filled sodium hyaluronate dressing, bacterial microorganisms carried by the sodium hyaluronate dry powder are killed by adopting a mode of introducing steam when the sodium hyaluronate solution is prepared, so that the sodium hyaluronate dressing with relatively low bacterial endotoxin level is prepared. The sodium hyaluronate dressing has good biocompatibility, the use safety of the product is further improved by controlling endotoxin indexes, the sodium hyaluronate dressing can be used for adjuvant therapy of superficial epidermis injuries such as laser / tartaric acid skin glowing / micro-plastic postoperative wounds, adverse reactions such as postoperative swelling, pain, scorching hot and dry skin of a patient can be reduced, and the application prospect is wide. Wound healing is accelerated, and the skin is tightened.

Description

Technical Field

[0001] The present invention belongs to the field of medical aesthetics, and specifically relates to a method for preparing a sodium hyaluronate dressing with low bacterial endotoxin. Background Art

[0002] In recent years, laser treatment, acid peeling, micro-plastic surgery and other light medical aesthetics have become the first choice for treating skin problems such as acne, pustules, papules, blackheads, skin aging, and improving skin conditions due to their characteristics of less trauma and quick recovery. However, while these treatments bring significant results, they can cause patients to experience adverse reactions such as redness, swelling, pain, burning, and dry skin. Therefore, the repair and care of wounds after medical aesthetics has become an important link that cannot be ignored.

[0003] Hyaluronic acid is a natural mucopolysaccharide, a high molecular weight polymer that makes up the extracellular matrix of skin tissue. It can enhance the expression of epidermal growth factor in skin tissue and increase the activity of fibrin, thereby promoting the skin barrier function. Based on the above mechanism, medical sodium hyaluronate dressing is a typical representative of skin repair in the field of medical cosmetology. It can significantly reduce the redness and swelling, burning pain of the skin after medical cosmetology, and accelerate wound healing. It has been widely used in clinical practice. The product is a viscous aqueous solution made of sodium hyaluronate, stabilizer, purified water, etc. in a certain proportion with non-woven fabric as the carrier. It works by adsorbing to the carrier.

[0004] Bacterial endotoxin is a unique structure of the cell wall of Gram-negative bacteria, and its main chemical component is lipopolysaccharide. The contact of bacterial endotoxin with the wound surface will cause local inflammatory response in patients, leading to symptoms such as redness, swelling, and pain. It will also affect the gene expression of skin fibroblasts and may induce the transformation of normal fibroblasts into hypertrophic scar fibroblasts. At present, on the raw material side, there is little control over the content of bacterial endotoxin in non-woven fabrics on the market, and Gram-negative bacteria that may be introduced into sodium hyaluronate during the production process will produce bacterial endotoxins when the bacteria autolyze or are lysed, which will cause the overall bacterial endotoxin content of medical sodium hyaluronate dressings to be high, affecting its safety and repair effect after medical cosmetic surgery. Therefore, it is very necessary to prepare a sodium hyaluronate dressing with low bacterial endotoxin. Summary of the invention

[0005] The object of the present invention is to provide a method for preparing a sodium hyaluronate dressing with low bacterial endotoxin to solve the above problems.

[0006] The present invention adopts the following technical solution:

[0007] The present invention discloses a method for preparing a sodium hyaluronate dressing with low bacterial endotoxin, comprising the following steps:

[0008] 1) Pretreatment of non-woven fabrics

[0009] After fixing multiple pieces of non-woven fabrics, place them in an alkaline solution for soaking. After the soaking is completed, transfer the non-woven fabrics to an ultrasonic cleaning machine and perform ultrasonic cleaning until neutral. After the cleaning is completed, take out the non-woven fabrics and squeeze them until no water is drained out. Then, lay the non-woven fabrics flat in a blast drying oven, dry them, fold them into bags, and finally seal them with sterile packaging for later use.

[0010] 2) Preparation of sodium hyaluronate solution

[0011] Weigh anhydrous disodium hydrogen phosphate Na2HPO4 and anhydrous sodium dihydrogen phosphate NaH2PO4 into purified water, stir until completely dissolved, then add sodium hyaluronate powder of a specific molecular weight, and pass steam while stirring to sterilize the solution online.

[0012] As a further improvement, the alkali solution in step 1) of the present invention is selected from one of sodium hydroxide and potassium hydroxide, and its concentration is 0.2wt% to 10wt%.

[0013] As a further improvement, during the online sterilization of the solution in step 2) of the present invention, the steam action time is 15 to 30 minutes and the steam action temperature is 121 to 135°C.

[0014] As a further improvement, the soaking time in step 1) of the present invention is 30 minutes to 72 hours.

[0015] As a further improvement, the ultrasonic frequency in step 1) of the present invention is 10KHz to 120KHz.

[0016] As a further improvement, the molecular weight of sodium hyaluronate in step 2) of the present invention is 300,000 to 500,000 Daltons.

[0017] The above technical solution has the following beneficial effects:

[0018] 1. The present invention proposes a method for preparing a sodium hyaluronate dressing with low bacterial endotoxin. The formula ingredients used are streamlined, and it does not contain additives such as alcohol, fluorescent agent, preservatives, etc., which is more friendly and safe to the skin.

[0019] 2. On the one hand, the present invention uses alkaline solution immersion to destroy the structure of bacterial endotoxins carried by the non-woven fabric material; on the other hand, steam is introduced during the preparation of the sodium hyaluronate solution to kill the bacterial microorganisms carried by the sodium hyaluronate dry powder, thereby controlling the source of bacterial endotoxin growth and preparing a sodium hyaluronate dressing with a lower bacterial endotoxin level, which can accelerate wound healing and further improve the safety of the product.

[0020] 3. The low bacterial endotoxin sodium hyaluronate dressing of the present invention has no pyrogenicity, no skin sensitization, no intradermal reaction, no acute systemic toxic reaction, and has good biocompatibility.

[0021] 4. The low bacterial endotoxin sodium hyaluronate dressing of the present invention can effectively reduce the symptoms of patients after cosmetic surgery, such as erythema, pain, edema, etc., and the patients' comfort / satisfaction evaluation is good or excellent.

[0022] 5. The low bacterial endotoxin sodium hyaluronate dressing of the present invention can form a breathable film on the skin surface to block the invasion of bacteria, dust, etc., lock the moisture on the skin surface, and prevent the wound surface from drying out.

[0023] 6. The sodium hyaluronate raw material used in the present invention is produced by bacterial fermentation, which avoids the risk of carrying viruses and transmission media when extracting animal tissues or organs.

[0024] 7. The concentration of the alkali solution in the present invention is 0.2wt% to 10wt%, and the soaking time is 30min to 72h, which can not only ensure that the tensile strength of the non-woven fabric meets the design standard, but also remove the bacterial endotoxins carried by the non-woven fabric.

[0025] 8. The steam action time for online solution sterilization in the present invention is 15 to 30 minutes, and the steam action temperature is 121 to 135°C, which can kill bacteria and microorganisms carried by sodium hyaluronate dry powder. The molecular weight of the selected sodium hyaluronate is 300,000 to 500,000 Daltons, which can ensure that the molecular weight of sodium hyaluronate can be maintained above 100,000 Daltons after being reduced under the action of steam. DETAILED DESCRIPTION

[0026] The technical solution of the present invention is further described below in conjunction with specific embodiments:

[0027] Embodiment 1:

[0028] (1) Pretreatment of non-woven fabrics: 2000 pieces of non-woven fabrics were divided into 40 stacks and fixed with cable ties, and then placed in a 2wt% sodium hydroxide solution for treatment for 24 h. The non-woven fabrics were then taken out and placed in an ultrasonic cleaning machine filled with purified water, and ultrasonically cleaned at a frequency of 30 kHz until neutral. After cleaning, the non-woven fabrics were taken out and squeezed until no water was drained out. They were then spread flat on the rack of a blast drying oven and baked at 80°C. After baking, the single piece of non-woven fabric was folded and placed in an aluminum foil bag, and finally double-sealed with a polyethylene bag for use.

[0029] (2) Preparation of sodium hyaluronate solution: 40 L of purified water was added to a batching tank, followed by weighing 12.8 g of anhydrous disodium hydrogen phosphate (Na2HPO4) and 5.2 g of anhydrous sodium dihydrogen phosphate (NaH2PO4) and adding them to the batching tank, stirring until completely dissolved, and then weighing 200 g of sodium hyaluronate dry powder with a viscosity-average molecular weight of 300,000 Daltons and adding it to the batching tank. While stirring, steam at 121° C. was passed into the batching tank for 15 min to sterilize the solution online.

[0030] (3) Filling of sodium hyaluronate solution: Add 18 mL of the sodium hyaluronate solution prepared in step (2) into the aluminum foil bag containing the non-woven fabric prepared in step (1), and finally set the temperature of the sealing machine to 180° C. for heat sealing to obtain a sodium hyaluronate dressing.

[0031] (4) Sterilization of sodium hyaluronate dressing: The sodium hyaluronate dressing prepared in step (3) is hung in a moist heat sterilizer, and the sterilization temperature is set to 121° C. and the sterilization time is set to 12 min. After sterilization, a sodium hyaluronate dressing that meets the endotoxin requirements can be obtained.

[0032] Embodiment 2:

[0033] (1) Pretreatment of non-woven fabrics: 1000 pieces of non-woven fabrics were divided into 20 stacks and fixed with cable ties, and then placed in a 4 wt % sodium hydroxide solution for 6 h. The non-woven fabrics were then taken out and placed in an ultrasonic cleaning machine filled with purified water, and ultrasonically cleaned at a frequency of 40 kHz until neutral. After cleaning, the non-woven fabrics were taken out and squeezed until no water was drained out, and then spread flat on the rack of a blast drying oven and baked at 40° C. After baking, the single piece of non-woven fabric was folded and put into an aluminum foil bag, which was double-sealed with a polyethylene bag and then sterilized with EO. After analysis, it was set aside.

[0034] (2) Preparation of sodium hyaluronate solution: Under the clean conditions required for aseptic processing, 20 L of purified water was measured and added to the batching tank. Subsequently, 7.2 g of anhydrous disodium hydrogen phosphate (Na2HPO4) and 3.4 g of anhydrous sodium dihydrogen phosphate (NaH2PO4) were weighed and added to the batching tank, and stirred until completely dissolved. Then, 104 g of sodium hyaluronate dry powder with a viscosity-average molecular weight of 360,000 Daltons was weighed and added to the batching tank. Steam at 121° C. was passed into the batching tank while stirring for 20 min to sterilize the solution online.

[0035] (3) Filling of sodium hyaluronate solution: Under the clean conditions required for aseptic processing, the sodium hyaluronate solution prepared in step (2) is filled using an automatic filling machine, with the filling volume set to 16 mL, the sealing time set to 2 s, and the sealing temperature set to 150° C. After the filling is completed, a sodium hyaluronate dressing that meets the endotoxin requirements can be obtained.

[0036] Embodiment 3:

[0037] (1) Pretreatment of non-woven fabrics: 1800 pieces of non-woven fabrics were divided into 30 stacks and fixed with cable ties, and then placed in a 1wt% sodium hydroxide solution for 24 h. The non-woven fabrics were then taken out and placed in an ultrasonic cleaning machine filled with purified water, and ultrasonically cleaned at a frequency of 60 kHz until neutral. After cleaning, the non-woven fabrics were taken out and squeezed until no water was drained out. They were then spread flat on the rack of a blast drying oven and baked at 70°C. After baking, the single piece of non-woven fabric was folded and placed in an aluminum foil bag, and finally double-sealed with a polyethylene bag for use.

[0038] (2) Preparation of sodium hyaluronate solution: 30 L of purified water was added to a batching tank, followed by weighing 10.5 g of anhydrous disodium hydrogen phosphate (Na2HPO4) and 4.8 g of anhydrous sodium dihydrogen phosphate (NaH2PO4) and adding them to the batching tank, stirring until completely dissolved, and then weighing 160 g of sodium hyaluronate dry powder with a viscosity-average molecular weight of 380,000 Daltons and adding it to the batching tank. While stirring, steam at 121° C. was passed into the batching tank for 16 min to sterilize the solution online.

[0039] (3) Filling of sodium hyaluronate solution: Add 15 mL of the sodium hyaluronate solution prepared in step (2) into the aluminum foil bag containing the non-woven fabric prepared in step (1), and finally set the temperature of the sealing machine to 180° C. for heat sealing to obtain a sodium hyaluronate dressing.

[0040] (4) Sterilization of sodium hyaluronate dressing: The sodium hyaluronate dressing prepared in step (3) is hung in a moist heat sterilizer, and the sterilization temperature is set to 121° C. and the sterilization time is set to 12 min. After sterilization, a sodium hyaluronate dressing that meets the endotoxin requirements can be obtained.

[0041] Embodiment 4:

[0042] (1) Pretreatment of non-woven fabrics: 3000 pieces of non-woven fabrics were divided into 40 stacks and fixed with cable ties, and then placed in a 6wt% sodium hydroxide solution for treatment for 8h. The non-woven fabrics were then taken out and placed in an ultrasonic cleaning machine filled with purified water, and ultrasonically cleaned at a frequency of 60KHz until neutral. After cleaning, the non-woven fabrics were taken out and squeezed until no water was drained out, and then spread flat on the rack of a blast drying oven and baked at 80°C. After baking, the single piece of non-woven fabric was folded and put into an aluminum foil bag, which was double-sealed with a polyethylene bag and then sterilized with EO. After analysis, it was set aside.

[0043] (2) Preparation of sodium hyaluronate solution: Under the clean conditions required for aseptic processing, 65 L of purified water was measured and added to the batching tank. Subsequently, 21.5 g of anhydrous disodium hydrogen phosphate (Na2HPO4) and 9.8 g of anhydrous sodium dihydrogen phosphate (NaH2PO4) were weighed and added to the batching tank, and stirred until completely dissolved. Then, 330 g of sodium hyaluronate dry powder with a viscosity-average molecular weight of 380,000 Daltons was weighed and added to the batching tank. Steam at 121° C. was passed into the batching tank while stirring for 18 minutes to sterilize the solution online.

[0044] (3) Filling of sodium hyaluronate solution: Under the clean conditions required for aseptic processing, the sodium hyaluronate solution prepared in step (2) is filled using an automatic filling machine, with the filling volume set to 20 mL, the sealing time set to 2 s, and the sealing temperature set to 160° C. After the filling is completed, a sodium hyaluronate dressing that meets the endotoxin requirements can be obtained.

[0045] Embodiment 5:

[0046] (1) Pretreatment of non-woven fabrics: 6000 pieces of non-woven fabrics were divided into 60 stacks and fixed with cable ties, and then placed in a 5wt% sodium hydroxide solution for 24 h. The non-woven fabrics were then taken out and placed in an ultrasonic cleaning machine filled with purified water, and ultrasonically cleaned at a frequency of 100 kHz until neutral. After the cleaning, the non-woven fabrics were taken out and squeezed until no water was drained out. They were then spread flat on the rack of a blast drying oven and baked at 70°C. After the baking was completed, the single piece of non-woven fabric was folded and placed in an aluminum foil bag, and finally double-sealed with a polyethylene bag for use.

[0047] (2) Preparation of sodium hyaluronate solution: 150 L of purified water was added to a batching tank, followed by weighing 54 g of anhydrous disodium hydrogen phosphate (Na2HPO4) and 25 g of anhydrous sodium dihydrogen phosphate (NaH2PO4) and adding them to the batching tank, stirring until completely dissolved, and then weighing 780 g of sodium hyaluronate dry powder with a viscosity-average molecular weight of 360,000 Daltons and adding it to the batching tank. While stirring, steam at 121° C. was passed into the batching tank for 16 min to sterilize the solution online.

[0048] (3) Filling of sodium hyaluronate solution: Add 25 mL of the sodium hyaluronate solution prepared in step (2) into the aluminum foil bag containing the non-woven fabric prepared in step (1), and finally set the temperature of the sealing machine to 180° C. for heat sealing to obtain a sodium hyaluronate dressing.

[0049] (4) Sterilization of sodium hyaluronate dressing: The sodium hyaluronate dressing prepared in step (3) is hung in a moist heat sterilizer, and the sterilization temperature is set to 121° C. and the sterilization time is set to 12 min. After sterilization, a sodium hyaluronate dressing that meets the endotoxin requirements can be obtained.

[0050] Embodiment 6:

[0051] (1) Pretreatment of non-woven fabrics: 3000 pieces of non-woven fabrics were divided into 30 stacks and fixed with cable ties, and then placed in a 2 wt % sodium hydroxide solution for treatment for 30 min. The non-woven fabrics were then taken out and placed in an ultrasonic cleaning machine filled with purified water, and ultrasonically cleaned at a frequency of 50 kHz until neutral. After cleaning, the non-woven fabrics were taken out and squeezed until no water was drained out, and then spread flat on the rack of a blast drying oven and baked at 80° C. After baking, the single piece of non-woven fabric was folded and placed in an aluminum foil bag, which was double-sealed with a polyethylene bag and then sterilized with EO. After analysis, it was set aside.

[0052] (2) Preparation of sodium hyaluronate solution: Under the clean conditions required for aseptic processing, 80 L of purified water was measured and added to the batching tank. Subsequently, 28 g of anhydrous disodium hydrogen phosphate (Na2HPO4) and 12.8 g of anhydrous sodium dihydrogen phosphate (NaH2PO4) were weighed and added to the batching tank, and stirred until completely dissolved. Then, 430 g of sodium hyaluronate dry powder with a viscosity-average molecular weight of 400,000 Daltons was weighed and added to the batching tank. Steam at 121° C. was passed into the batching tank while stirring for 20 min to sterilize the solution online.

[0053] (3) Filling of sodium hyaluronate solution: Under the clean conditions required for aseptic processing, the sodium hyaluronate solution prepared in step (2) is filled using an automatic filling machine, with the filling volume set to 25 mL, the sealing time set to 2 s, and the sealing temperature set to 150° C. After the filling is completed, a sodium hyaluronate dressing that meets the endotoxin requirements can be obtained.

[0054] Comparative Example 1: The nonwoven fabric is not pretreated, and other processes are the same as in Example 1.

[0055] Comparative Example 2: The sodium hyaluronate solution was not sterilized online, and the other processes were the same as in Example 1.

[0056] Biological index detection and clinical evaluation methods

[0057] (1) Bacterial endotoxin: Use a horseshoe crab reagent with a sensitivity of 0.015EU / mL to test the test solution for bacterial endotoxin. Take an appropriate amount of sodium hyaluronate dressing extrudate, dilute it with pyrogen-free endotoxin test water (not exceeding MVD), shake well, and use it as the test sample. Take the test solution and operate according to the gel method.

[0058] (2) Cytotoxicity: Appropriate extracts were contacted with cultured cells, and corresponding control solutions were contacted with cultured cells. After 24 h of contact, the growth and morphological changes of the test cells were observed under an inverted microscope, the absorbance value of each group was measured, and the cell survival rate was calculated.

[0059] (3) Pyrogenicity: The test samples were extracted with sterile pyrogen-free 0.9% sodium chloride injection (SC). The sample extract was injected into three test rabbits via the ear vein at a dose of 10 ml / kg. The rectal temperature of the test rabbits was measured and recorded every 30 minutes within 3 hours after the injection.

[0060] (4) Sensitization: The test sample was applied locally to induce skin sensitization. The control sample was applied locally to 5 guinea pigs in the same way. After induction, the test group and control group animals were stimulated by application of the corresponding sample. The skin reactions of all stimulated sites of the test group and control group animals were graded 24h and 48h after the removal of the patch.

[0061] (5) Intradermal reaction: The test samples were extracted in 0.9% sodium chloride injection (SC) and cottonseed oil (CSO) to prepare extracts, and control solutions without test samples were prepared in the same way. Each sample extract and the corresponding solvent control solution were injected intradermally on both sides of the rabbit spine, and the erythema and edema at the injection site were scored 24h, 48h and 72h after injection, and the difference in the average score of intradermal reaction between the test sample and the corresponding solvent control was calculated.

[0062] (6) Acute systemic toxicity: The test samples were extracted in 0.9% sodium chloride injection (SC) and cottonseed oil (CSO) to prepare extracts, and a control solution without the test sample was prepared in the same way. The test sample extracts were injected into mice via the peritoneal route, and the 0.9% sodium chloride injection extract and control solution, and the vegetable oil extract and control solution were injected into the peritoneal cavity respectively. After the injection, the immediate reaction of the animals was observed, and the general condition, toxicity manifestations and number of dead animals of the test group and the control group were observed and recorded at 4h, 24h, 48h and 72h. The weight of the animals was weighed and recorded at the initial, 24h, 48h and 72h.

[0063] (7) Clinical method: A clinical non-inferiority comparison study was conducted between the low bacterial endotoxin sodium hyaluronate dressing of the present invention and the sodium hyaluronate dressing of the marketed product to verify the effectiveness and safety of the use of this product.

[0064] Table 1. Comparison of bacterial endotoxin levels in sodium hyaluronate products on the market

[0065] Product Name Classification Bacterial endotoxins Comparative Case 1 / Positive Comparative Case 2 / Positive S1 / Negative S2 / Negative S3 / Negative S4 / Negative S5 / Negative S6 / Negative Commercially available products 1 Class II medical devices Positive Commercially available product 2 Class II medical devices Positive Commercially available product 3 cosmetic Positive Commercially available products 4 cosmetic Positive

[0066] Note: When the bacterial endotoxin level is greater than 0.5EU / mL, it is positive; when the bacterial endotoxin level is less than 0.5EU / mL, it is negative.

[0067] The above results indicate that the bacterial endotoxin level of the sodium hyaluronate dressing prepared by the present invention is less than 0.5EU / mL, which is lower than that of commercially available products. In addition, it is impossible to prepare a sodium hyaluronate dressing with a low level of bacterial endotoxin by only using a method of pre-treating the non-woven fabric to destroy its bacterial endotoxin-carrying structure or only using a method of online sterilization of the sodium hyaluronate preparation to control the growth of bacterial endotoxin. Only when the two are combined can the bacterial endotoxin be controlled to a level less than 0.5EU / mL.

[0068] S1 Biocompatibility Data:

[0069] (1) Cytotoxicity:

[0070]

[0071]

[0072] (2) Pyrogenicity:

[0073]

[0074] (3) Allergenicity:

[0075]

[0076]

[0077] Note: Grade 0 represents no obvious changes; Grade 1 represents scattered or macular erythema; Grade 2 represents moderate confluent erythema; Grade 3 represents severe erythema and / or edema

[0078] (4) Intradermal reaction:

[0079]

[0080]

[0081] Note: No erythema is scored as 0; very mild erythema (barely visible) is scored as 1; clear erythema is scored as 2; moderate erythema is scored as 3; severe erythema (purple-red) to eschar formation where erythema grading is impossible is scored as 4; no edema is scored as 0; very mild edema (barely visible) is scored as 1; clear edema (clear edge of swelling) is scored as 2; moderate edema (swelling of about 1 mm) is scored as 3; severe edema (swelling of more than 1 mm and beyond the contact area) is scored as 4; the highest score for irritation is 8.

[0082] (5) Acute systemic toxicity:

[0083]

[0084]

[0085] Note: “—” indicates normal, no toxic reaction was observed.

[0086] The above results show that the low bacterial endotoxin sodium hyaluronate dressing of the present invention has good biocompatibility: when the mouse fibroblast L-929 is used to evaluate its cytotoxicity, the cell survival rate is as high as 92.7% after the sample extract and the cells are co-cultured for 24 hours, and the product has no potential cytotoxicity; its pyrogenicity, sensitization, intradermal reaction, and acute systemic toxicity are evaluated by mice and rabbits, and the results show that the sodium hyaluronate dressing prepared by the present invention has no pyrogenicity, no skin sensitization, no intradermal reaction, and no acute systemic toxic reaction.

[0087] S1 Clinical Data:

[0088] Semi-quantitative scoring of acute inflammatory reactions such as erythema, edema, and burning

[0089]

[0090]

[0091] Note: 0 points means no erythema, edema, or burning sensation; 1 point means visible erythema but no edema or burning sensation; 2 points means obvious erythema and burning sensation, mild edema, and slight burning pain; 3 points means obvious erythema, edema, burning sensation, burning pain, and punctate bleeding or exudation.

[0092] D14 Comfort / Satisfaction Evaluation

[0093]

[0094] Clinical data show that the low bacterial endotoxin sodium hyaluronate dressing of the present invention can effectively reduce the erythema, pain, edema and other symptoms of patients after medical aesthetics. The patients had certain skin lesions after laser surgery before treatment. After using the sodium hyaluronate dressing of the present invention for 3 days, 7 days, and 14 days, the symptoms such as erythema, pain, edema and the like began to gradually decrease, and the scabs also gradually decreased. After 14 days, most patients returned to normal, and the patients' comfort / satisfaction evaluations were all good or excellent.

[0095] The above are only specific embodiments of the present invention, but the technical features of the present invention are not limited thereto. Any simple changes, equivalent replacements or modifications made based on the present invention to solve basically the same technical problems and achieve basically the same technical effects are all included in the protection scope of the present invention.

Claims

1. A method for preparing a sodium hyaluronate dressing with low bacterial endotoxin, characterized in that: The steps include: 1) Pretreatment of non-woven fabrics After fixing multiple pieces of non-woven fabrics, place them in an alkaline solution for soaking. After the soaking is completed, transfer the non-woven fabrics to an ultrasonic cleaning machine and perform ultrasonic cleaning until neutral. After the cleaning is completed, take out the non-woven fabrics and squeeze them until no water is drained out. Then, lay the non-woven fabrics flat in a blast drying oven, dry them, fold them into bags, and finally seal them with sterile packaging for later use. 2) Preparation of sodium hyaluronate solution Weigh anhydrous disodium hydrogen phosphate Na2HPO4 and anhydrous sodium dihydrogen phosphate NaH2PO4 into purified water, stir until completely dissolved, then add sodium hyaluronate powder of a specific molecular weight, and pass steam while stirring to sterilize the solution online.

2. The method for preparing the low bacterial endotoxin sodium hyaluronate dressing according to claim 1, characterized in that: The alkali solution in step 1) is selected from sodium hydroxide and potassium hydroxide, and its concentration is 0.2wt% to 10wt%.

3. The method for preparing the low bacterial endotoxin sodium hyaluronate dressing according to claim 1, characterized in that: During the online sterilization of the solution in step 2), the steam action time is 15 to 30 minutes, and the steam action temperature is 121 to 135°C.

4. The method for preparing the low bacterial endotoxin sodium hyaluronate dressing according to claim 1, characterized in that: The soaking time in step 1) is 30 minutes to 72 hours.

5. The method for preparing the low bacterial endotoxin sodium hyaluronate dressing according to claim 1, characterized in that: The ultrasonic frequency in step 1) is 10KHz to 120KHz.

6. The method for preparing the sodium hyaluronate dressing with low bacterial endotoxin according to claim 1, 2, 3, 4 or 5, characterized in that: The molecular weight of sodium hyaluronate in step 2) is 300,000 to 500,000 Daltons.

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