CN115845127A - Polysaccharide hemostatic repair biological glue solution and preparation method and application thereof - Google Patents
Polysaccharide hemostatic repair biological glue solution and preparation method and application thereof Download PDFInfo
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- CN115845127A CN115845127A CN202211708385.8A CN202211708385A CN115845127A CN 115845127 A CN115845127 A CN 115845127A CN 202211708385 A CN202211708385 A CN 202211708385A CN 115845127 A CN115845127 A CN 115845127A
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- biological glue
- glue solution
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- sodium carboxymethylcellulose
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- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 46
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- 239000005017 polysaccharide Substances 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 50
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Landscapes
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medical dressings, and particularly relates to polysaccharide hemostatic repair biological glue solution, and a preparation method and application thereof. The biological glue solution has the effects of quickly stopping bleeding, promoting healing, preventing adhesion, assisting repair and inhibiting bacteria. Preferably, the biological glue solution is prepared from the following raw materials in percentage by weight: 0.1-3% of sodium carboxymethylcellulose, 1-5% of sulglicotide, 0.8-2% of sodium chloride, and water for injection to 100%, wherein the sodium carboxymethylcellulose is high-substitution-degree sodium carboxymethylcellulose, and the substitution degree of the sodium carboxymethylcellulose is 1.3-1.5. The experimental result shows that the polysaccharide hemostatic and repair biological glue solution has good safety, biocompatibility, hemostatic and repair performance and excellent bacteriostatic activity.
Description
Technical Field
The invention belongs to the technical field of medical dressings, and particularly relates to polysaccharide hemostatic repair biological glue solution, and a preparation method and application thereof.
Background
At present, in the field of clinical medicine, the wound surface or the operation incision of trauma needs to be washed, and the clinical application is common by using normal saline, but the normal saline washing only can physically wash and clean the wound surface, and cannot play the effects of quickly stopping bleeding, promoting healing, preventing adhesion, assisting in repair and inhibiting bacteria. Many patients have the problems that the wound surface of trauma or the incision after operation is delayed and difficult to heal, and even postoperative adhesion, postoperative infection and the like occur, so that great physical and psychological pain is caused to the patients. Therefore, how to effectively control the blood seepage of capillary vessels and venules in a body cavity and the seepage of a tissue wound surface so as to avoid the occurrence of an adhesion phenomenon and how to control the infection of wound tissues become more and more widely concerned in the industry.
Adhesions are abnormal structures formed by the binding of fibrous bands of connective tissue to adjacent tissues or organs. The formation of adhesions is common and it has been reported that 65% to 95% of abdominal and pelvic surgeries can result in varying degrees of adhesion. Which increases the difficulty of re-surgery and the potential for further complications. The purpose of adhesion prevention is to eliminate or reduce the incidence and severity of adhesions while ensuring normal wound healing and avoiding infection.
Infection is the most common complication after surgery, mainly caused by the exposure of the tissue wound to unclean environment and the proliferation of bacteria in the tissue wound and the interior. The current clinical mode of combating infections is primarily prophylactic use of anti-infective drugs, but the consequence of this is increased bacterial resistance to anti-infective drugs, which in severe cases can lead to treatment failure of the patient.
As described above, the currently and mainly used irrigation fluids in clinical practice generally cannot achieve the effects of stopping bleeding rapidly, promoting healing, preventing adhesion, assisting repair and inhibiting bacteria at the same time, so that a safe and degradable medical dressing capable of stopping bleeding rapidly, promoting healing, preventing adhesion, assisting repair and inhibiting bacteria to further assist in reducing the risk of the operation may be more needed while improving the surgical operation technology in clinical practice.
Polysaccharides extracted from plants have been widely used in clinical practice in recent years, and their hemostatic and anti-adhesion effects have been gradually discovered. For example, many relevant papers have been reported on the anti-adhesion test of carmellose sodium in hemostasis. Carboxymethyl cellulose (CMC) is a high molecular linear polysaccharide obtained by chemically modifying natural cellulose, has the characteristics of no toxicity, good biocompatibility, degradability, renewability and hygroscopicity, and is one of the most important water-soluble cellulose derivatives at present. CMC molecule can form a three-dimensional space network structure in water solution, and is mainly used as a novel anti-adhesion material in the medical field. CMC is formed by replacing the hydrogen atom of the hydroxyl group on the glucose ring of cellulose with carboxymethyl, and the substitution Degree (DS) of CMC refers to the moleculeWherein the hydroxyl group (-OH) on each glucoside unit is substituted by sodium carboxymethyl (-CH) through an ether bond 2 COONa) as a substitute. The substitution degree is one of the most important indexes for measuring the quality of the CMC, and the CMC with different substitution degrees has different application aspects due to different solubility, adsorptivity, acid precipitation pH value, salt resistance, enzymolysis property and the like. The degree of substitution of carboxymethyl cellulose ethers mainly sold on the market at present is between 0.6 and 1.2. The carboxymethyl cellulose with ultrahigh substitution degree has wider substitution degree and viscosity range, higher storage stability and thermal stability, better acid and alkali resistance and salt resistance, better rheological property and smaller thixotropy, and has gradually become a common use trend at home and abroad.
However, the use of plant-derived polysaccharides alone as functional surgical irrigation dressings generally solves only the problems of hemostasis and adhesion prevention, generally has no bacteriostatic action, and has weak healing and repair promoting effects. At present, quaternary ammonium salt or other clinically common antibacterial agents are added into certain polysaccharide hemostatic biological glue solution to enable the polysaccharide hemostatic biological glue solution to have an antibacterial effect, but the quaternary ammonium salt or other clinically common antibacterial agents generally have certain irritation, are not easy to accept by patients when used for open wounds, and easily generate toxicity when the dosage is large, so that the application of the scheme in medical supplies, particularly functional surgical irrigation dressings is limited.
The inventor unexpectedly discovers that mucopolysaccharide substance sulglicotide can be added into plant polysaccharide biological glue solution through a large amount of basic research and screening, the sulglicotide has a unique chemical structure, can form a layer of protective film on the wound surface, can protect the normal biological activity of the tissue, promotes the repair of the epithelium, the mucosa and the wound surface of the tissue, and has good antibacterial activity. At present, no relevant report on the combined use of the two in the technical field of medical dressings is found.
Disclosure of Invention
In order to overcome the defects of the prior art and solve the technical problems in the prior art, the invention provides polysaccharide hemostasis repair biological glue solution, a preparation method and application thereof, wherein the biological glue solution preferably contains sodium carboxymethylcellulose and sulglicotide. The polysaccharide hemostatic and repair biological glue solution has good safety, biocompatibility, hemostatic and repair performance and excellent bacteriostatic activity.
Specifically, the invention is realized by the following technical schemes:
in a first aspect, the invention provides polysaccharide hemostatic repair biological glue solution, which is prepared from the following raw materials in percentage by weight: 0.1-3% of sodium carboxymethylcellulose, 0.8-2% of sodium chloride, and water for injection to 100%, wherein the sodium carboxymethylcellulose is high-substitution-degree sodium carboxymethylcellulose, and the substitution degree of the sodium carboxymethylcellulose is 1.3-1.5.
Preferably, the degree of substitution of the sodium carboxymethylcellulose is 1.4.
Alternatively, in the biogum liquid, the biogum liquid has the effects of rapidly stopping bleeding, promoting healing, preventing adhesion, assisting repair and inhibiting bacteria.
As an optional mode, in the biological glue solution, the biological glue solution is prepared from the following raw materials in percentage by weight: 0.1 to 3 percent of sodium carboxymethylcellulose, 1 to 5 percent of sulglicotide, 0.8 to 2 percent of sodium chloride and water for injection to 100 percent.
As an optional mode, in the biological glue solution, the biological glue solution is prepared from the following raw materials in percentage by weight: 1 to 1.5 percent of sodium carboxymethylcellulose, 1 to 3 percent of sulglicotide, 0.85 to 0.95 percent of sodium chloride and water for injection to 100 percent.
As an optional mode, in the biological glue solution, the biological glue solution is prepared from the following raw materials in percentage by weight: 1.5 percent of sodium carboxymethylcellulose, 2 percent of sulglicotide, 0.9 percent of sodium chloride and water for injection to 100 percent.
Optionally, in the biogum liquid, the glycopeptide may be glycopeptide, and the glycopeptide may be obtained by extracting glycopeptide from pig duodenum or gastric mucosa and performing sulfonation treatment.
Preferably, the sulglicotide has a CAS number of 54182-59-1, which is available directly from purchase.
As an alternative mode, in the biological glue solution, the preparation method of the sodium carboxymethyl cellulose comprises the following steps:
step 1: under the condition of room temperature, taking an isopropanol/ethanol solution with the mass concentration of 70-80% as a solvent, adding cellulose, after the cellulose is dissolved, adding a NaOH aqueous solution with the mass concentration of 40-50%, controlling the temperature at 40-50 ℃, stirring and alkalizing for 40-60min, wherein the isopropanol/ethanol solution is a mixed solution consisting of 80% by weight of isopropanol and 20% by weight of ethanol, and the weight ratio of the isopropanol/ethanol solution, the cellulose and the NaOH aqueous solution is 8-10;
step 2: slowly adding chloroacetic acid/ethanol solution with the mass concentration of 70-80% into the solution obtained by the reaction, wherein the chloroacetic acid/ethanol solution is a mixed solution consisting of 60% of chloroacetic acid and 40% of ethanol in percentage by weight, the weight ratio of the chloroacetic acid/ethanol solution to the cellulose is 4-5;
and step 3: adding 40-50% NaOH aqueous solution, heating to 75-80 ℃ for secondary etherification reaction, keeping the temperature for reaction for 1.5-2h, wherein the molar ratio of the NaOH aqueous solution added in the previous two times to the NaOH aqueous solution added in the next two times is 1.5-2;
and 4, step 4: neutralizing the obtained product with acetic acid to pH =7-8, washing with 70-80% ethanol water solution for three times to remove reaction by-products, and drying in a vacuum drying oven at 80-100 deg.C for 4-5h to obtain sodium carboxymethylcellulose with high substitution degree.
In a second aspect, the present invention provides a method for preparing a biogum liquid according to the first aspect, comprising the following steps:
step 1: weighing various raw materials except for water for injection according to the formula amount, adding the raw materials into a liquid preparation tank, and adding the water for injection to 100% for later use;
step 2: uniformly stirring the solution obtained in the step (1) at the rotating speed of 800-1000rpm, standing for 5 hours, and performing suction filtration by using a filter element to obtain a clear solution for later use;
and step 3: filling the clear solution obtained in the step 2 into a soft bag or a glass bottle according to the required specification and sealing to obtain an initial product for later use;
and 4, step 4: and (4) sterilizing the primary product obtained in the step (3), and packaging after sterilization.
Preferably, the desired specification is 40mL, 50mL, 60mL, 80mL, 100mL, 120mL, 200mL, 250mL, 300mL, 350mL, 500mL, or 1000mL.
In a third aspect, the invention provides the use of the biological glue solution of the first aspect or the biological glue solution prepared by the preparation method of the second aspect in preparing a functional surgical irrigation dressing.
As an optional mode, in the above uses, the functional surgical irrigation dressing has the effects of rapidly stopping bleeding, promoting healing, preventing adhesion, assisting repair and inhibiting bacteria, is suitable for various surgical irrigation, lavage and cleaning, and treatment and repair of wound surfaces, mucous membranes and skin, can play a role in lubricating, isolating and biologically shielding tissue wound surfaces, mucous membranes and skin, effectively prevents blood seepage, has an antibacterial effect, and is also used as a sustained-release carrier of a pharmaceutical preparation.
Alternatively, in the above use, the functional surgical irrigating dressing is used for direct irrigation or used for covering, applying or wet dressing a wound surface after infiltration with a sterile dressing.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. For reasons of space, they will not be described in detail.
Compared with the prior art, the invention has the following beneficial effects:
the invention provides polysaccharide hemostatic repair biological glue solution, which preferably comprises sodium carboxymethylcellulose and sulglicotide. The polysaccharide hemostatic and repairing biological glue solution has good safety, biocompatibility, hemostatic and repairing performances, and excellent bacteriostatic activity. The inventor unexpectedly discovers that the combination of the carboxymethylcellulose and the sulglicotide in a specific dosage proportion has an obvious synergistic effect in the research process, compared with the single use of the carboxymethylcellulose sodium biological glue solution, the single use of the sulglicotide flushing fluid and the physiological saline has very excellent technical effects in the aspects of flushing effect, bacteriostatic effect, adverse reaction, biocompatibility, moisture retention property, hemostatic property, repair effect and the like, overcomes the defects of the functional surgical flushing dressing clinically used at present, and has very high technical advancement and clinical practical value.
Detailed Description
The invention is further illustrated with reference to specific examples. It should be understood that the specific embodiments described herein are illustrative only and are not limiting upon the scope of the invention.
The examples do not show the specific techniques or conditions, according to the technical or conditions described in the literature in the field, or according to the product specifications. The reagents or instruments used are conventional products which are not known to manufacturers and are available from normal sources.
The experimental procedures in the following examples are conventional unless otherwise specified. The test materials used in the following examples are all commercially available products unless otherwise specified.
Preparation examples:
example 1
The polysaccharide hemostatic repair biological glue solution is prepared from the following raw materials in percentage by weight: 1.5% of sodium carboxymethyl cellulose, 2% of sulglicotide, 0.9% of sodium chloride, and water for injection to 100%, wherein the sodium carboxymethyl cellulose is sodium carboxymethyl cellulose with high degree of substitution, and the degree of substitution of the sodium carboxymethyl cellulose is 1.4.
The preparation method of the sodium carboxymethyl cellulose comprises the following steps:
step 1: under the condition of room temperature, taking an isopropanol/ethanol solution with the mass concentration of 75% as a solvent, adding cellulose, after the cellulose is dissolved, adding a NaOH aqueous solution with the mass concentration of 45%, controlling the temperature at 40 ℃, stirring and alkalizing for 50min, wherein the isopropanol/ethanol solution is a mixed solution consisting of 80% by weight of isopropanol and 20% by weight of ethanol, and the weight ratio of the isopropanol/ethanol solution to the cellulose to the NaOH aqueous solution is 9;
and 2, step: slowly adding chloroacetic acid/ethanol solution with the mass concentration of 75% into the solution obtained by the reaction, wherein the chloroacetic acid/ethanol solution is a mixed solution consisting of 60% of chloroacetic acid and 40% of ethanol in percentage by weight, the weight ratio of the chloroacetic acid/ethanol solution to the cellulose is 4.5;
and 3, step 3: then adding a NaOH aqueous solution with the mass concentration of 45%, heating to 75 ℃ to carry out secondary etherification reaction, keeping the temperature for reaction for 1.5h, wherein the molar ratio of the NaOH aqueous solutions added in the previous two times to the NaOH aqueous solution added in the next two times is 1.5;
and 4, step 4: neutralizing the obtained product with acetic acid until the pH is =7-8, washing with 70% ethanol water solution for three times to remove reaction byproducts, and drying in a vacuum drying oven at 80 ℃ for 4h to obtain the sodium carboxymethyl cellulose with high substitution degree.
The preparation method of the biological glue solution comprises the following steps:
step 1: weighing various raw materials except for water for injection according to the formula amount, adding the raw materials into a liquid preparation tank, and adding the water for injection to 100% for later use;
step 2: uniformly stirring the solution obtained in the step 1 at a rotating speed of 900rpm, standing for 5 hours, and performing suction filtration by using a filter element to obtain a clear solution for later use;
and step 3: filling the clear solution obtained in the step 2 into a soft bag or a glass bottle according to the required specification and sealing to obtain an initial product for later use;
and 4, step 4: and (4) sterilizing the primary product obtained in the step (3), and packaging after sterilization.
Comparative example 1
The polysaccharide hemostatic repair biological glue solution is prepared from the following raw materials in percentage by weight: 1.5 percent of sodium carboxymethyl cellulose, 0.9 percent of sodium chloride, and water for injection is added to 100 percent, wherein the sodium carboxymethyl cellulose is sodium carboxymethyl cellulose with high degree of substitution, and the degree of substitution of the sodium carboxymethyl cellulose is 1.4.
Comparative example 1 sodium carboxymethylcellulose was used as in example 1, except that sulglicotide was not included, and comparative example 1 was prepared in the same manner as in example 1.
Comparative example 2
The biological glue solution for hemostasis and repair is prepared from the following raw materials in percentage by weight: 2% sulglicotide, 0.9% sodium chloride, and water for injection to 100%.
Comparative example 2 was prepared as in example 1, except that sodium carboxymethylcellulose was not included.
Comparative example 3
The polysaccharide hemostatic repair biological glue solution is prepared from the following raw materials in percentage by weight: 1.5 percent of sodium carboxymethylcellulose, 2 percent of sulglicotide, 0.9 percent of sodium chloride, and water for injection to 100 percent, wherein the substitution degree of the sodium carboxymethylcellulose is 0.8.
Comparative example 3 was prepared in the same manner as in example 1.
Comparative example 4
Only 0.9% sodium chloride solution.
Comparative example 5
Positive control: kaidia (polysaccharide cellulose hemostatic isolation repair glue solution), tokyo donwan biotechnology limited.
Effect embodiment:
the polysaccharide hemostatic repair biological glue solution prepared in the example 1 and the comparative examples 1-3 is subjected to a conventional animal skin irritation test, a skin sensitization test and an in vitro cytotoxicity test respectively. The result shows that the polysaccharide hemostatic repair biological glue solution is safe and nontoxic.
Effect example 1: the polysaccharide hemostatic repairing biological glue solution has the antibacterial effect
The test is carried out according to a conventional inhibition zone experiment, and escherichia coli, bacillus subtilis, aspergillus niger and saccharomycetes are used as target test bacteria. The experimental results are shown in table 1 below.
Table 1: antibacterial experimental result of polysaccharide hemostatic repair biological glue solution
The results of bacteriostatic experiments show that the polysaccharide hemostatic repair biological glue solution (example 1) can achieve a good bacteriostatic effect when in use, the diameter of the bacteriostatic ring of the example 1 is obviously superior to that of the carboxymethyl cellulose sodium biological glue solution (comparative example 1) and the sulglicotide flushing solution (comparative example 2), and the combined use of the high-substitution-degree carboxymethyl cellulose sodium and the sulglicotide can generate a very good synergistic bacteriostatic effect. In addition, the polysaccharide hemostatic repair biological glue solution has an effective inhibition effect on various fungi and bacteria, and shows an excellent broad-spectrum antibacterial effect. Therefore, the polysaccharide hemostatic repair biological glue solution is applied to the wound surface, so that the risk of wound surface or incision infection can be reduced, a better environment is created for wound surface or incision healing, the use of antibiotics is reduced, and the generation of drug resistance is avoided.
In addition, the polysaccharide hemostatic repair biological glue solution (example 1) of the invention has a significantly better bacteriostatic action than the similar products sold in the market (comparative example 5) as a positive control. From the experimental results of comparative example 3, it can be seen that the bacteriostatic effect of using the sodium carboxymethyl cellulose with high degree of substitution is superior to that of the sodium carboxymethyl cellulose with low degree of substitution. As can be seen from the experimental results of comparative example 4, the 0.9% sodium chloride solution used alone has substantially no bacteriostatic effect.
Effect example 2: the polysaccharide hemostatic repair biological glue solution has the wound surface hemostatic effect
The cleaning grade ICR mice of 6-8 weeks old were purchased from the medical laboratory animal center in guangdong province, the raising temperature was maintained at 25 ± 5 ℃, the relative humidity was maintained at 50 ± 10%, the light and shade alternation was 7. All mice were fed regular maintenance feed and autoclaved water and the animals were acclimated in the animal house for one week prior to the experiment.
The experiment was divided into 6 groups, example 1 group and comparative examples 1-5 group.
1. The experimental method comprises the following steps:
(1) Taking 36 healthy male mice for the experiment, weighing 18 +/-22 g, and 6 mice per group, carrying out intraperitoneal injection anesthesia by using a 3.5% chloral hydrate solution, and placing the mice in a fixer for tail shearing experiment after 3-5min of anesthesia.
(2) Comparing the hemostasis time of the mice in each group: the length of the tail is cut to be about 1cm, medical gauze which is dipped in each group of sample solution to be tested (example 1 and comparative examples 1-5) is wound after the tail is cut, the pressure is lightly pressed, the bleeding starting time and the bleeding stopping time are recorded, the bleeding stopping time is the time when the wound stops bleeding, and in the whole experiment process, the tail of the mouse is wiped to seep blood every 10 seconds until no blood flows out of the wound.
2. The experimental results are as follows:
the results of the wound surface hemostatic effect of the polysaccharide hemostatic and repair biological glue solution are shown in table 2.
Table 2: experimental result of wound surface hemostatic effect of polysaccharide hemostatic repair biological glue solution
The experimental result of the wound hemostasis effect shows that the polysaccharide hemostasis repair biological glue solution (example 1) can achieve a good wound hemostasis effect when in use, the hemostasis time of the example 1 is obviously shorter than that of the single use of sodium carboxymethylcellulose biological glue solution (comparative example 1) and the single use of sulglicotide flushing fluid (comparative example 2), and the combined use of the sodium carboxymethylcellulose with high substitution degree and the sulglicotide can generate a very good synergistic hemostasis effect.
In addition, the wound surface hemostatic effect of the polysaccharide hemostatic and repair biological glue solution (example 1) is obviously better than that of the similar products sold in the market (comparative example 5) used as a positive control. From the experimental results of comparative example 3, it can be seen that the wound surface hemostatic effect using the high-substitution degree sodium carboxymethyl cellulose is superior to that of the low-substitution degree sodium carboxymethyl cellulose. As can be seen from the experimental results of comparative example 4, the use of the 0.9% sodium chloride solution alone has substantially no hemostatic effect on the wound surface.
Effect example 3: the polysaccharide hemostatic repair biological glue solution has the effect of preventing postoperative intestinal adhesion
The cleaning grade Wistar rats of 6-8 weeks old are purchased from the centers of medical experimental animals in Guangdong province, the breeding temperature is kept at 25 +/-5 ℃, the relative humidity is kept at 50 +/-10%, and the light and shade alternation is 7. All rats were fed regular maintenance feed and autoclaved water and the animals were acclimated in the animal house for one week prior to the experiment.
The experiment was divided into 6 groups, example 1 group and comparative examples 1-5 group.
1. The experimental method comprises the following steps:
(1) Taking 48 healthy male rats for the experiment, weighing 180 +/-220 g, carrying out intraperitoneal injection anesthesia on 8 mice in each group by using a 3.5% chloral hydrate solution, and carrying out various experimental operations after the anesthesia is successful;
(2) Fixing anesthetized animals on the back, shearing hairs on the abdomen, disinfecting with 1.0% iodophor solution, cutting a 2-3cm incision in the middle of the lower abdomen under aseptic conditions, opening the abdominal cavity of a rat to find out the ileocecal part, and annularly peeling off the ileum serosa at a position 3-4cm away from the ileocecal part to form an annular bleeding wound surface of about 5 cm; injecting 5mL of each group of sample solution to be tested (example 1 and comparative examples 1-5) into the abdominal cavity of each group of animals, placing the sample solution back into the abdominal cavity, and suturing the abdominal cavity;
(3) Fasting for 12h after operation, and feeding in cages according to the standard; and (5) treating the animals by the 14 th day after the operation, performing open abdominal material drawing inspection, and judging the adhesion grade according to the adhesion grading standard.
The blocking grade classification criteria are as follows:
grade 0 is no adhesion to abdominal cavity; the I level is loose adhesion between the intestinal wound surface and omentum majus, peritoneum and mesentery, and is easy to separate and has no bleeding; the II level is that the adhesion of the intestinal canal wound surface and omentum majorana, peritoneum and mesentery is more compact than the I level, the separation is more difficult than the I level, and the wound surface oozes blood; the III grade is wide and compact in adhesion, separable, slightly dilated in a proximal segment of intestinal canal and free of intestinal obstruction; grade IV is extensive, compact, lumpy, not easy to separate, and the near segment of the intestinal canal expands in the whole course, causing incomplete or complete intestinal obstruction. 2. The experimental results are as follows:
the experimental results of the effect of preventing postoperative intestinal adhesion of the polysaccharide hemostatic repair biogum solution of the present invention are shown in table 3.
Table 3: experimental result of effect of polysaccharide hemostatic repair biogel solution on preventing postoperative intestinal adhesion
The experimental result of the effect of preventing postoperative intestinal adhesion shows that the polysaccharide hemostatic repair biological glue solution (example 1) can achieve a very good anti-adhesion effect, the adhesion incidence rate of the group of example 1 is significantly lower than that of the single use of the carboxymethylcellulose sodium biological glue solution (comparative example 1) and the single use of the sulglicotide flushing fluid (comparative example 2), and the combined use of the carboxymethylcellulose sodium with high substitution degree and the sulglicotide can generate a very good synergistic effect of preventing postoperative intestinal adhesion.
In addition, the polysaccharide hemostatic repair biogum solution (example 1) of the invention is significantly better than the similar product on the market (comparative example 5) as a positive control in preventing postoperative intestinal adhesion. As can be seen from the experimental results of comparative example 3, the effect of preventing postoperative intestinal adhesion using carboxymethyl cellulose with a high degree of substitution is superior to that of carboxymethyl cellulose with a low degree of substitution. As can be seen from the experimental results of comparative example 4, the use of the 0.9% sodium chloride solution alone has substantially no effect of preventing postoperative intestinal adhesion.
In conclusion, the polysaccharide hemostatic and repair biological glue solution has good safety, biocompatibility, hemostatic and repair performance, and excellent bacteriostatic activity.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.
Claims (10)
1. A polysaccharide hemostatic repair biological glue solution is characterized in that: the biological glue solution is prepared from the following raw materials in percentage by weight: 0.1-3% of sodium carboxymethylcellulose, 0.8-2% of sodium chloride, and water for injection to 100%, wherein the sodium carboxymethylcellulose is high-substitution-degree sodium carboxymethylcellulose, and the substitution degree of the sodium carboxymethylcellulose is 1.3-1.5.
2. The biogum liquid as claimed in claim 1, characterized in that: the biological glue solution has the effects of quickly stopping bleeding, promoting healing, preventing adhesion, assisting repair and inhibiting bacteria.
3. The biogum solution according to claim 1 or claim 2, wherein: the biological glue solution is prepared from the following raw materials in percentage by weight: 0.1 to 3 percent of sodium carboxymethylcellulose, 1 to 5 percent of sulglicotide, 0.8 to 2 percent of sodium chloride and water for injection to 100 percent.
4. The biogum solution according to claim 3, wherein: the biological glue solution is prepared from the following raw materials in percentage by weight: 1 to 1.5 percent of sodium carboxymethylcellulose, 1 to 3 percent of sulglicotide, 0.85 to 0.95 percent of sodium chloride and water for injection to 100 percent.
5. The biogum solution according to claim 3 or claim 4, wherein: the sulglicotide is a glycopeptide substance, and is obtained by extracting glycopeptide from pig duodenum or gastric mucosa and sulfonating the glycopeptide.
6. The biogum liquid as claimed in any one of claims 1 to 5, wherein: the preparation method of the sodium carboxymethyl cellulose comprises the following steps:
step 1: under the condition of room temperature, taking an isopropanol/ethanol solution with the mass concentration of 70-80% as a solvent, adding cellulose, after the cellulose is dissolved, adding a NaOH aqueous solution with the mass concentration of 40-50%, controlling the temperature at 40-50 ℃, stirring and alkalizing for 40-60min, wherein the isopropanol/ethanol solution is a mixed solution consisting of 80% by weight of isopropanol and 20% by weight of ethanol, and the weight ratio of the isopropanol/ethanol solution, the cellulose and the NaOH aqueous solution is 8-10;
and 2, step: slowly adding chloroacetic acid/ethanol solution with the mass concentration of 70-80% into the solution obtained by the reaction, wherein the chloroacetic acid/ethanol solution is a mixed solution consisting of 60% of chloroacetic acid and 40% of ethanol in percentage by weight, the weight ratio of the chloroacetic acid/ethanol solution to the cellulose is 4-5;
and step 3: then adding 40-50% NaOH aqueous solution, heating to 75-80 ℃ for secondary etherification reaction, keeping the temperature for reaction for 1.5-2h, wherein the molar ratio of the NaOH aqueous solution added in the previous two times to the NaOH aqueous solution added in the next two times is 1.5-2;
and 4, step 4: neutralizing the obtained product with acetic acid to pH =7-8, washing with 70-80% ethanol water solution for three times to remove reaction by-products, and drying in a vacuum drying oven at 80-100 deg.C for 4-5h to obtain sodium carboxymethylcellulose with high substitution degree.
7. The process for preparing biogum liquor according to any one of claims 1 to 6, wherein: the method comprises the following steps:
step 1: weighing various raw materials except for water for injection according to the formula amount, adding the raw materials into a liquid preparation tank, and adding the water for injection to 100% for later use;
and 2, step: uniformly stirring the solution obtained in the step 1 at a rotating speed of 800-1000rpm, standing for 5 hours, and performing suction filtration by using a filter element to obtain a clear solution for later use;
and 3, step 3: filling the clear solution obtained in the step 2 into a soft bag or a glass bottle according to the required specification and sealing to obtain an initial product for later use;
and 4, step 4: and (4) sterilizing the primary product obtained in the step (3), and packaging after sterilization.
8. Use of the biogum liquid of any one of claims 1 to 6 or prepared by the preparation method of claim 7 in the preparation of functional surgical irrigation dressings.
9. Use according to claim 8, characterized in that: the functional surgical irrigation dressing has the effects of quickly stopping bleeding, promoting healing, preventing adhesion, assisting repair and inhibiting bacteria, is suitable for various surgical irrigation, lavage and cleaning, and treatment and repair of wound surfaces, mucous membranes and skin, can play roles of lubricating, isolating and biologically shielding on tissue wound surfaces, mucous membranes and skin, effectively prevents blood seepage, has an antibacterial effect, and can also be used as a sustained-release carrier of a pharmaceutical preparation.
10. Use according to claim 8 or claim 9, characterized in that: the functional surgical irrigation dressing is used for directly irrigating or covering, applying or wet-compressing a wound surface after being infiltrated by a sterile dressing.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010055615A1 (en) * | 1999-04-16 | 2001-12-27 | Donald G. Wallace | Rapid gelling biocompatible polymer composition |
| US20080234180A1 (en) * | 2004-05-18 | 2008-09-25 | Tium Spa | Use of Sulgliocotide for the Treatment of Mucositis |
| CN105126158A (en) * | 2015-07-23 | 2015-12-09 | 南京东万生物技术有限公司 | Polysaccharides-cellulose haemostatic, isolating, antibacterial and repairing glue solution and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010055615A1 (en) * | 1999-04-16 | 2001-12-27 | Donald G. Wallace | Rapid gelling biocompatible polymer composition |
| US20080234180A1 (en) * | 2004-05-18 | 2008-09-25 | Tium Spa | Use of Sulgliocotide for the Treatment of Mucositis |
| CN105126158A (en) * | 2015-07-23 | 2015-12-09 | 南京东万生物技术有限公司 | Polysaccharides-cellulose haemostatic, isolating, antibacterial and repairing glue solution and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 体育院、系教材编审委员会: "《人体医学参数与概念》", vol. 1, 人民教育出版社, pages: 165 * |
| 汤日玲等: "硫酸糖肽的生物活性及药理作用", 《生命的化学》, vol. 30, no. 2, pages 3 - 4 * |
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