CN115845127B - 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
- Publication number
- CN115845127B CN115845127B CN202211708385.8A CN202211708385A CN115845127B CN 115845127 B CN115845127 B CN 115845127B CN 202211708385 A CN202211708385 A CN 202211708385A CN 115845127 B CN115845127 B CN 115845127B
- Authority
- CN
- China
- Prior art keywords
- solution
- carboxymethyl cellulose
- biological glue
- glue solution
- sodium carboxymethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000003364 biologic glue Substances 0.000 title claims abstract description 55
- 230000002439 hemostatic effect Effects 0.000 title claims abstract description 47
- 150000004676 glycans Chemical class 0.000 title claims abstract description 42
- 229920001282 polysaccharide Polymers 0.000 title claims abstract description 42
- 239000005017 polysaccharide Substances 0.000 title claims abstract description 42
- 230000008439 repair process Effects 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 239000000243 solution Substances 0.000 claims abstract description 112
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 53
- 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 51
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 46
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 46
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 30
- 230000000694 effects Effects 0.000 claims abstract description 30
- 238000006467 substitution reaction Methods 0.000 claims abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000002994 raw material Substances 0.000 claims abstract description 18
- 239000008215 water for injection Substances 0.000 claims abstract description 18
- 230000000740 bleeding effect Effects 0.000 claims abstract description 12
- 230000035876 healing Effects 0.000 claims abstract description 10
- 239000011780 sodium chloride Substances 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 24
- 239000000047 product Substances 0.000 claims description 17
- 229920002678 cellulose Polymers 0.000 claims description 16
- 239000001913 cellulose Substances 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 12
- 229940106681 chloroacetic acid Drugs 0.000 claims description 12
- 230000023597 hemostasis Effects 0.000 claims description 11
- 230000002262 irrigation Effects 0.000 claims description 10
- 238000003973 irrigation Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 9
- 230000001954 sterilising effect Effects 0.000 claims description 9
- 210000001519 tissue Anatomy 0.000 claims description 9
- 102000002068 Glycopeptides Human genes 0.000 claims description 8
- 108010015899 Glycopeptides Proteins 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 8
- 238000006266 etherification reaction Methods 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 230000002195 synergetic effect Effects 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- 238000011049 filling Methods 0.000 claims description 4
- 239000011521 glass Substances 0.000 claims description 4
- 210000004400 mucous membrane Anatomy 0.000 claims description 4
- 238000004806 packaging method and process Methods 0.000 claims description 4
- 238000007789 sealing Methods 0.000 claims description 4
- 238000004659 sterilization and disinfection Methods 0.000 claims description 4
- 238000000967 suction filtration Methods 0.000 claims description 4
- 230000003113 alkalizing effect Effects 0.000 claims description 3
- 239000006227 byproduct Substances 0.000 claims description 3
- 238000004140 cleaning Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 230000003472 neutralizing effect Effects 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 230000004888 barrier function Effects 0.000 claims description 2
- 210000001198 duodenum Anatomy 0.000 claims description 2
- 210000001156 gastric mucosa Anatomy 0.000 claims description 2
- 230000001050 lubricating effect Effects 0.000 claims description 2
- 238000006277 sulfonation reaction Methods 0.000 claims description 2
- 241000282887 Suidae Species 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 15
- 241000894006 Bacteria Species 0.000 abstract description 6
- 230000001737 promoting effect Effects 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 206010052428 Wound Diseases 0.000 description 31
- 208000027418 Wounds and injury Diseases 0.000 description 30
- 230000000052 comparative effect Effects 0.000 description 29
- 238000002474 experimental method Methods 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 10
- 108010027529 Bio-glue Proteins 0.000 description 9
- 238000011010 flushing procedure Methods 0.000 description 9
- 230000002980 postoperative effect Effects 0.000 description 9
- 206010000050 Abdominal adhesions Diseases 0.000 description 8
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 7
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 7
- 229940105329 carboxymethylcellulose Drugs 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 5
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 206010002091 Anaesthesia Diseases 0.000 description 4
- 210000001015 abdomen Anatomy 0.000 description 4
- 210000000683 abdominal cavity Anatomy 0.000 description 4
- 230000037005 anaesthesia Effects 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 239000008354 sodium chloride injection Substances 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 238000005520 cutting process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 238000010171 animal model Methods 0.000 description 2
- 230000002924 anti-infective effect Effects 0.000 description 2
- 230000003385 bacteriostatic effect Effects 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
- 229960002327 chloral hydrate Drugs 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 208000003243 intestinal obstruction Diseases 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000002747 omentum Anatomy 0.000 description 2
- 210000004303 peritoneum Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 206010067268 Post procedural infection Diseases 0.000 description 1
- 206010060932 Postoperative adhesion Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 241000235342 Saccharomycetes Species 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 206010070835 Skin sensitisation Diseases 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical group CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 125000004395 glucoside group Chemical group 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000000713 mesentery Anatomy 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 231100000370 skin sensitisation Toxicity 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000000264 venule Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medical dressing, and in particular relates to polysaccharide hemostatic repair biological glue solution, and a preparation method and application thereof. The biological glue solution has the effects of stopping bleeding rapidly, 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 carboxymethyl cellulose, 1% -5% of thioglycopeptide and 0.8% -2% of sodium chloride, and adding water for injection to 100%, wherein the sodium carboxymethyl cellulose is sodium carboxymethyl cellulose with high substitution degree, and the substitution degree of the sodium carboxymethyl cellulose is 1.3-1.5. Experimental results show that the polysaccharide hemostatic repair biological glue solution not only has good safety, biocompatibility, hemostatic and repair properties, but also has excellent antibacterial activity.
Description
Technical Field
The invention belongs to the technical field of medical dressing, and in particular relates to polysaccharide hemostatic repair biological glue solution, and a preparation method and application thereof.
Background
At present, in the clinical medicine field, the trauma wound surface or the operation incision needs to be washed, the clinical application is common in normal saline, but the normal saline washing can only play a role in physically washing the wound surface or the incision and cleaning the wound surface, and can not play the roles of quickly stopping bleeding, promoting healing, preventing adhesion, assisting repair and inhibiting bacteria. Many patients can have trauma wound surfaces or postoperative incisions which are delayed and difficult to heal, even have postoperative adhesion, postoperative infection and other conditions, and cause great physical and psychological pain to the patients. Therefore, how to effectively control the blood permeation of capillaries and venules in a body cavity and the blood permeation of tissue wound surfaces, thereby avoiding the occurrence of adhesion phenomenon, and how to control the infection of wound tissues become a problem of increasing attention in the industry.
Adhesions are abnormal structures of connective tissue fibrous tapes that join adjacent tissues or organs. Adhesion formation is common, and 65% -95% of abdominal and pelvic surgery has been reported to result in varying degrees of adhesion. Which increases the difficulty of re-surgery and the potential for further complications. The purpose of preventing adhesion is to eliminate or reduce the incidence and severity of adhesion while ensuring normal wound healing and avoiding infection.
Infection is the most common complication after surgery, mainly due to exposure of the tissue wound to unclean environment, bacteria propagating on and in the tissue wound. The current clinically common way to combat infections is mainly 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 patient treatment failure.
As described above, the currently mainly used flushing liquid in clinic generally cannot simultaneously achieve the effects of rapid hemostasis, healing promotion, adhesion prevention, auxiliary repair and bacteriostasis, so that a novel medical dressing which is safe and degradable, and simultaneously can rapidly stop bleeding, promote healing, prevent adhesion, auxiliary repair and bacteriostasis to further assist in reducing the risk of surgery may be more needed while the surgical operation technology is improved in clinic.
Polysaccharide components extracted from plants are widely applied to clinic in recent years, and the hemostatic and anti-adhesion effects of the polysaccharide components are gradually discovered. As a series of related papers have been reported on sodium carboxymethylcellulose hemostasis anti-adhesion tests. Carboxymethyl cellulose (CMC) is a high molecular linear polysaccharide obtained by chemical modification of natural cellulose, has the characteristics of no toxicity, good biocompatibility, degradability, regenerability and hygroscopicity, and is one of the most important water-soluble cellulose derivatives at present. CMC molecules can form a three-dimensional space network structure in aqueous solution, and are mainly used as a novel anti-adhesion material in the medical field. CMC is formed by substituting 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 substitution degree of the hydroxyl group (-OH) on each glucoside unit in the molecule with sodium carboxymethyl (-CH) through ether bond 2 COONa) are substituted. The substitution degree is one of the most important indexes for measuring the quality of CMC, and CMC with different substitution degrees has different application aspects due to different solubility, adsorptivity, pH value of acid precipitation, salt resistance, enzymolysis property and the like. The degree of substitution of the carboxymethyl cellulose ether which is mainly sold in the market at present is between 0.6 and 1.2. The ultrahigh-substitution-degree carboxymethyl cellulose 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 thixotropic propertySex has become a general use trend at home and abroad.
However, the use of plant-extracted polysaccharides alone as functional surgical irrigation dressings generally only solves the problems of hemostasis and adhesion prevention, generally does not have antibacterial action, and has weak effect of promoting healing and repair. At present, certain polysaccharide hemostatic biological glue solutions are added with quaternary ammonium salt or other clinically common antibacterial agents to ensure that the polysaccharide hemostatic biological glue solutions have antibacterial effect, but the quaternary ammonium salt or other clinically common antibacterial agents usually have certain irritation, are not easy to accept by patients when being used for open wounds and are easy to generate toxicity when the dosage is large, so that the application of the scheme in medical supplies, particularly functional surgical irrigation dressing, is limited.
Through a great deal of basic research and screening, the inventor surprisingly discovers that the glycosaminoglycan substance, namely the thioglycopeptide, can be added into plant polysaccharide biological glue solution, has a unique chemical structure, can form a layer of protective film on a wound surface, can protect normal biological activity of tissues, promotes repair of epithelial, mucosal and tissue wound surfaces, and has good antibacterial activity. At present, no related report of the combined use of the two in the technical field of medical dressing is known.
Disclosure of Invention
In order to overcome the defects in the prior art and solve the technical problems in the prior art, the invention provides a polysaccharide hemostatic repair biological glue solution, a preparation method and application thereof, wherein the biological glue solution preferably comprises sodium carboxymethylcellulose and thioglycopeptides. The polysaccharide hemostatic repair biological glue solution has good safety, biocompatibility, hemostatic and repair properties and excellent antibacterial activity.
Specifically, the invention is realized through the following technical schemes:
in a first aspect, the invention provides a polysaccharide hemostatic repair bio-glue solution, which is prepared from the following raw materials in percentage by weight: 0.1% -3% of sodium carboxymethyl cellulose and 0.8% -2% of sodium chloride, adding water for injection to 100%, wherein the sodium carboxymethyl cellulose is sodium carboxymethyl cellulose with high substitution degree, and the substitution degree of the sodium carboxymethyl cellulose is 1.3-1.5.
Preferably, the sodium carboxymethyl cellulose has a degree of substitution of 1.4.
Alternatively, in the above-mentioned bio-glue solution, the bio-glue solution has the effects of rapid hemostasis, healing promotion, adhesion prevention, auxiliary repair and bacteriostasis.
Alternatively, in the above bio-glue solution, the bio-glue solution is prepared from the following raw materials in percentage by weight: 0.1 to 3 percent of sodium carboxymethyl cellulose, 1 to 5 percent of thioglycopeptide and 0.8 to 2 percent of sodium chloride, and water for injection is added to 100 percent.
Alternatively, in the above bio-glue solution, the bio-glue solution is prepared from the following raw materials in percentage by weight: 1 to 1.5 percent of sodium carboxymethyl cellulose, 1 to 3 percent of thioglycopeptide and 0.85 to 0.95 percent of sodium chloride, and water for injection is added to 100 percent.
Alternatively, in the above bio-glue solution, the bio-glue solution is prepared from the following raw materials in percentage by weight: 1.5% of sodium carboxymethyl cellulose, 2% of thioglycopeptide and 0.9% of sodium chloride, and water for injection is added to 100%.
Alternatively, in the above-mentioned biological glue solution, the thio-glycopeptides are glycopeptides, and the thio-glycopeptides are obtained by extracting glycopeptides from the duodenum or gastric mucosa of a pig and then sulfonation.
Preferably, the thioglycopeptide has a CAS number of 54182-59-1, which is commercially available.
Alternatively, in the above 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 an NaOH aqueous solution with the mass concentration of 40-50%, controlling the temperature at 40-50 ℃, and 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 8-10:1:1.5-3;
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% by weight of chloroacetic acid and 40% by weight of ethanol, the weight ratio of the chloroacetic acid/ethanol solution to cellulose is 4-5:1, stirring and mixing for 20-30min, heating the mixed solution to 60-70 ℃ for etherification reaction, and reacting for 2-2.5h;
step 3: adding 40-50% NaOH aqueous solution, heating to 75-80 ℃ for secondary etherification reaction, and keeping the temperature for reaction for 1.5-2h, wherein the molar ratio of the NaOH aqueous solution added before and after the reaction is 1:1.5-2;
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 byproducts, and drying in a vacuum drying oven at 80-100deg.C for 4-5 hr to obtain sodium carboxymethylcellulose with high substitution degree.
In a second aspect, the present invention provides a method for preparing the biological glue solution according to the first aspect, which comprises the following steps:
step 1: weighing various raw materials except for water for injection in a formula amount, adding the raw materials into a liquid preparation tank, and adding the water for injection to 100% for standby;
step 2: stirring the solution obtained in the step 1 at a constant speed of 800-1000rpm, standing for 5 hours, and carrying out suction filtration by using a filter element to obtain a clear solution for later use;
step 3: filling the clarified solution obtained in the step 2 into a soft bag or a glass bottle according to the required specification, and sealing to obtain a primary product for later use;
step 4: and (3) 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 a biological glue solution according to the first aspect or a biological glue solution prepared by a preparation method according to the second aspect in the preparation of a functional surgical irrigation dressing.
In the above-mentioned application, the described functional surgical irrigation dressing possesses the functions of quickly stopping bleeding, promoting healing, preventing adhesion, auxiliary repairing and inhibiting bacteria, and is applicable to various surgical irrigation, lavage and cleaning, and can be used for treating and repairing wound surface, mucous membrane and skin, and can possesses the functions of lubricating isolation and biological barrier for tissue wound surface, mucous membrane and skin, can effectively prevent bleeding and possesses bacteriostasis, also can be used as slow-release carrier of medicine preparation.
Alternatively, in the above-described use, the functional surgical irrigation dressing is used to directly irrigate or cover, smear or wet-coat a wound surface after infiltration with a sterile dressing.
It is understood that within the scope of the present invention, the above-described technical features of the present invention and technical features specifically described below (e.g., in the examples) may be combined with each other to constitute new or preferred technical solutions. Is limited to a space and will not be described in detail herein.
Compared with the prior art, the invention has the following beneficial effects:
the invention provides a polysaccharide hemostatic repair biological glue solution, which preferably comprises sodium carboxymethyl cellulose and thioglycopeptide. The polysaccharide hemostatic repair biological glue solution has good safety, biocompatibility, hemostatic and repair properties and excellent antibacterial activity. The inventor surprisingly finds that the combination of the carboxymethyl cellulose and the thioglycopeptide with the specific dosage ratio has obvious synergistic effect in the research process, and compared with the single use of the carboxymethyl cellulose sodium biological glue solution, the single use of the thioglycopeptide flushing liquid and the physiological saline has very excellent technical effects in the aspects of flushing effect, bacteriostasis effect, adverse reaction, biocompatibility, moisturizing performance, hemostatic performance, repairing effect and the like, solves the defects of the traditional clinically used functional operation flushing dressing, and has very high technical advancement and clinical practical value.
Detailed Description
The invention will be further illustrated with reference to specific examples. It should be understood that the detailed description and specific examples are intended for purposes of illustration only and are not intended to limit the scope of the invention.
The specific techniques or conditions are not identified in the examples and are described in the literature in this field or are carried out in accordance with the product specifications. The reagents or equipment used were conventional products available for purchase through regular channels, with no manufacturer noted.
The experimental methods in the following examples are conventional methods unless otherwise specified. The test materials used in the examples described below, unless otherwise specified, are all commercially available products.
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 glycopeptide, 0.9% of sodium chloride, and adding water for injection to 100%, wherein the sodium carboxymethyl cellulose is sodium carboxymethyl cellulose with high substitution degree, and the substitution degree 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, adding an NaOH aqueous solution with the mass concentration of 45% after the cellulose is dissolved, controlling the temperature at 40 ℃, and 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, the cellulose and the NaOH aqueous solution is 9:1:2;
step 2: 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% by weight of chloroacetic acid and 40% by weight of ethanol, the weight ratio of the chloroacetic acid/ethanol solution to the cellulose is 4.5:1, stirring and mixing for 30min, and heating the mixed solution to 65 ℃ for etherification reaction for 2h;
step 3: adding NaOH aqueous solution with the mass concentration of 45%, heating to 75 ℃ for secondary etherification reaction, and keeping the temperature for reaction for 1.5 hours, wherein the mol ratio of the NaOH aqueous solution added before and after the reaction is 1:1.5;
step 4: neutralizing the obtained product with acetic acid to pH=7-8, washing with 70% ethanol water solution for three times to remove reaction byproducts, and drying in a vacuum drying oven at 80deg.C for 4 hr to obtain sodium carboxymethylcellulose 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 in a formula amount, adding the raw materials into a liquid preparation tank, and adding the water for injection to 100% for standby;
step 2: stirring the solution obtained in the step 1 at a constant speed of 900rpm, standing for 5 hours, and carrying out suction filtration by using a filter element to obtain a clear solution for later use;
step 3: filling the clarified solution obtained in the step 2 into a soft bag or a glass bottle according to the required specification, and sealing to obtain a primary product for later use;
step 4: and (3) 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% of sodium carboxymethyl cellulose and 0.9% of sodium chloride, and adding water for injection to 100%, wherein the sodium carboxymethyl cellulose is sodium carboxymethyl cellulose with high substitution degree, and the substitution degree of the sodium carboxymethyl cellulose is 1.4.
The sodium carboxymethyl cellulose used in comparative example 1 was the same as in example 1, except that the glycopeptide contained therein was not included, and the preparation method of comparative example 1 was the same as in example 1.
Comparative example 2
The hemostatic repair biological glue solution is prepared from the following raw materials in percentage by weight: 2% of thioglycopeptide and 0.9% of sodium chloride, and water for injection is added 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% of sodium carboxymethyl cellulose, 2% of glycopeptide, 0.9% of sodium chloride, and adding water for injection to 100%, wherein the substitution degree of the sodium carboxymethyl cellulose 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: kagakuda (polysaccharide cellulose hemostatic isolation repair glue solution), nanjing Dongwang Biotechnology Co., ltd.
Effect examples:
the polysaccharide hemostatic repair biological glue solution prepared in the embodiment 1 and the polysaccharide hemostatic repair biological glue solution prepared in the comparative embodiment 1-3 are respectively subjected to conventional animal skin irritation test, skin sensitization test and in-vitro cytotoxicity test. The results show that the polysaccharide hemostatic repair biological glue solution is safe and nontoxic.
Effect example 1: the polysaccharide of the invention has the antibacterial effect of stopping bleeding and repairing biological glue solution
The test is carried out according to a conventional bacteriostasis circle 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 repairing biological glue solution
The antibacterial experiment result shows that the polysaccharide hemostatic repairing biological glue solution (example 1) can achieve a good antibacterial effect when being used, and the diameter of the antibacterial circle of the example 1 is obviously better than that of the carboxymethyl cellulose sodium biological glue solution (comparative example 1) and the sulfenide flushing solution (comparative example 2) which are used independently, so that the synergistic antibacterial effect is generated by the combined use of the carboxymethyl cellulose sodium with high substitution degree and the sulfenide flushing solution. In addition, the polysaccharide hemostatic repair biological glue solution provided by the invention has an effective inhibition effect on various fungi and bacteria, and has an excellent broad-spectrum antibacterial effect. Therefore, the polysaccharide hemostatic repairing biological glue solution is applied to the wound surface, can reduce the risk of wound surface or incision infection, creates a better environment for wound surface or incision healing, reduces the use of antibiotics and avoids the generation of drug resistance.
In addition, the antibacterial effect of the polysaccharide hemostatic and repairing biological glue solution (example 1) is obviously superior to that of the commercial similar product (comparative example 5) serving as a positive control. As can be seen from the experimental results of comparative example 3, the bacteriostatic effect using the sodium carboxymethyl cellulose with high substitution degree is superior to that of the sodium carboxymethyl cellulose with low substitution degree. As can be seen from the experimental results of comparative example 4, the 0.9% sodium chloride solution alone has substantially no bacteriostatic effect.
Effect example 2: the polysaccharide of the invention has the effect of stopping bleeding and repairing wound surface of biological glue solution
Clean ICR mice of 6-8 weeks old were purchased from medical laboratory animal centers in Guangdong province, kept at 25+ -5deg.C and 50+ -10% relative humidity, with light and shade alternation of 7:00-19:00 for daytime and 19:00-7:00 for nighttime. All mice were fed normal maintenance feed and high temperature sterilized water and animals were acclimatized in the animal house for one week prior to the experiment.
The experiments were divided into 6 groups, example 1 and comparative examples 1-5.
1. The experimental method comprises the following steps:
(1) 36 healthy male mice for the experiment are taken, the weight is 18+/-22 g, 6 mice in each group are subjected to intraperitoneal injection anesthesia by using 3.5% chloral hydrate solution, and after 3-5min of anesthesia, the mice are placed in a fixer for tail cutting experiment.
(2) Hemostatic time of mice in each group was compared: the tail was cut to a length of about 1cm, and after cutting, the tail was wrapped with a medical gauze dipped with each set of sample solutions to be tested (example 1 and comparative examples 1-5), lightly pressed and the bleeding start and stop times were recorded, the stop times being the times when the wound stopped bleeding, and the tail of the mice was wiped every 10 seconds for bleeding until no blood was shed from the wound during the whole experiment.
2. Experimental results:
the wound hemostatic effect results of the polysaccharide hemostatic repair biological glue solution of the invention are shown in table 2.
Table 2: the experimental result of the wound surface hemostatic effect of the polysaccharide hemostatic repair biological glue solution
The experimental result of the wound hemostasis effect shows that the polysaccharide hemostasis repairing biological glue solution (example 1) can achieve good wound hemostasis effect when being used, the hemostasis time of example 1 is obviously lower than that of the single use of the carboxymethyl cellulose sodium biological glue solution (comparative example 1) and the single use of the sulfenide flushing solution (comparative example 2), and the combined use of the high substitution degree carboxymethyl cellulose sodium and the sulfenide flushing solution can generate good synergistic hemostasis effect.
In addition, the wound surface hemostatic effect of the polysaccharide hemostatic repair biological glue solution (example 1) is obviously better than that of the commercial similar product (comparative example 5) serving as a positive control. From the experimental results of comparative example 3, it can be seen that the wound hemostatic effect using the high-substitution-degree sodium carboxymethyl cellulose is superior to that of the low-substitution-degree sodium carboxymethyl cellulose. From the experimental results of comparative example 4, it can be seen that 0.9% sodium chloride solution alone has substantially no wound hemostatic effect.
Effect example 3: the polysaccharide hemostatic and repairing biological glue solution has the effect of preventing postoperative intestinal adhesion
Clean Wistar rats of 6-8 weeks old are purchased from medical laboratory animal centers of Guangdong province, the raising temperature is kept at 25+/-5 ℃, the relative humidity is kept at 50+/-10%, the light and shade alternation is 7:00-19:00 for daytime and 19:00-7:00 for night. All rats were fed normal maintenance feed and high temperature sterilized water and animals were acclimatized in the animal house for one week prior to the experiment.
The experiments were divided into 6 groups, example 1 and comparative examples 1-5.
1. The experimental method comprises the following steps:
(1) Taking 48 healthy male rats for experiments, 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 the anesthetized animal on the back, shearing the abdomen, sterilizing with 1.0% iodophor solution, cutting 2-3cm incision in the middle of lower abdomen under aseptic condition, opening the abdominal cavity of the rat to find the ileocecal part, and circularly stripping ileum serosa at the position 3-4cm away from the ileocecal part to form a circular bleeding wound surface 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 abdomen;
(3) Fasted for 12 hours after operation, and standard feeding in separate cages; by the 14 th day after operation, animals are treated, the materials are obtained for examination at the beginning of the abdomen, and the adhesion grade is judged according to the adhesion grading standard.
The adhesion grade classification criteria are as follows:
grade 0 is that the abdominal cavity is not adhered; the grade I is loose adhesion between the intestinal canal wound surface and the large omentum, the peritoneum and the mesenterium, and is easy to separate and has no blood seepage; the II level is that the adhesion between the intestinal canal wound surface and the large omentum, the peritoneum and the mesentery is denser than the I level, and the separation is more difficult than the I level, and the wound surface is permeated; the III grade is widely and densely adhered, can be separated, and has slight expansion of the proximal intestinal canal and no intestinal obstruction; grade IV is widely adhered, compact, in a block shape, not easy to separate, and the proximal intestinal canal is expanded in the whole process, so that incomplete or complete intestinal obstruction is caused. 2. Experimental results:
the experimental results of the effect of the polysaccharide hemostatic and repairing biological glue solution in preventing postoperative intestinal adhesion are shown in table 3.
Table 3: the experimental result of the effect of the polysaccharide hemostatic and repairing biological glue solution on preventing postoperative intestinal adhesion
Experimental results of the postoperative intestinal adhesion prevention effect show that the polysaccharide hemostatic and repairing biological glue solution (example 1) can achieve a very good adhesion prevention effect, and the adhesion incidence rate of the group of examples 1 is remarkably lower than that of the group of examples 1 by singly using sodium carboxymethyl cellulose biological glue solution (comparative example 1) and the group of examples 2 by singly using thioglycopeptide flushing solution (comparative example 2), so that the synergistic effect of the postoperative intestinal adhesion prevention effect is achieved by jointly using sodium carboxymethyl cellulose with high substitution degree and the thioglycopeptide.
In addition, the polysaccharide hemostatic and repairing biological glue solution (example 1) has obviously better effect of preventing postoperative intestinal adhesion than the commercial similar product (comparative example 5) serving as a positive control. As can be seen from the experimental results of comparative example 3, the effect of preventing postoperative intestinal adhesion using sodium carboxymethyl cellulose with high substitution degree is superior to that of sodium carboxymethyl cellulose with low substitution degree. As can be seen from the experimental results of comparative example 4, the 0.9% sodium chloride solution alone has substantially no effect of preventing postoperative intestinal adhesion.
In conclusion, the polysaccharide hemostatic repair biological glue solution has good safety, biocompatibility, hemostatic and repair properties and excellent antibacterial activity.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention also include such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.
Claims (5)
1. A polysaccharide hemostatic repair biological glue solution with the effects of rapid hemostasis, healing promotion, adhesion prevention, auxiliary repair and bacteriostasis is characterized in that: the biological glue solution is prepared from the following raw materials in percentage by weight: 1.5 percent of sodium carboxymethyl cellulose, 2 percent of thioglycopeptide and 0.9 percent of sodium chloride, adding water for injection to 100 percent, wherein the sodium carboxymethyl cellulose is sodium carboxymethyl cellulose with high substitution degree, the substitution degree of the sodium carboxymethyl cellulose is 1.4, the combination of the sodium carboxymethyl cellulose and the thioglycopeptide has obvious synergistic effect,
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, adding an NaOH aqueous solution with the mass concentration of 45% after the cellulose is dissolved, controlling the temperature at 40 ℃, and 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, the cellulose and the NaOH aqueous solution is 9:1:2;
step 2: 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% by weight of chloroacetic acid and 40% by weight of ethanol, the weight ratio of the chloroacetic acid/ethanol solution to the cellulose is 4.5:1, stirring and mixing for 30min, and heating the mixed solution to 65 ℃ for etherification reaction for 2h;
step 3: adding NaOH aqueous solution with the mass concentration of 45%, heating to 75 ℃ for secondary etherification reaction, and keeping the temperature for reaction for 1.5 hours, wherein the mol ratio of the NaOH aqueous solution added before and after the reaction is 1:1.5;
step 4: neutralizing the obtained product with acetic acid to pH=7-8, washing with 70% ethanol water solution for three times to remove reaction byproducts, drying in a vacuum drying oven at 80deg.C for 4 hr to obtain sodium carboxymethylcellulose 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 in a formula amount, adding the raw materials into a liquid preparation tank, and adding the water for injection to 100% for standby;
step 2: stirring the solution obtained in the step 1 at a constant speed of 900rpm, standing for 5 hours, and carrying out suction filtration by using a filter element to obtain a clear solution for later use;
step 3: filling the clarified solution obtained in the step 2 into a soft bag or a glass bottle according to the required specification, and sealing to obtain a primary product for later use;
step 4: and (3) sterilizing the primary product obtained in the step (3), and packaging after sterilization.
2. The biological glue solution according to claim 1, characterized in that: the thio glycopeptides are glycopeptides, and are obtained by extracting glycopeptides from the duodenum or gastric mucosa of pigs and performing sulfonation treatment.
3. A method for preparing a biological glue solution according to claim 1 or claim 2, characterized in that: the method comprises the following steps:
step 1: weighing various raw materials except for water for injection in a formula amount, adding the raw materials into a liquid preparation tank, and adding the water for injection to 100% for standby;
step 2: stirring the solution obtained in the step 1 at a constant speed of 900rpm, standing for 5 hours, and carrying out suction filtration by using a filter element to obtain a clear solution for later use;
step 3: filling the clarified solution obtained in the step 2 into a soft bag or a glass bottle according to the required specification, and sealing to obtain a primary product for later use;
step 4: and (3) sterilizing the primary product obtained in the step (3), and packaging after sterilization.
4. Use of a biological glue according to claim 1 or claim 2 or prepared by the preparation method according to claim 3 for the preparation of a functional surgical irrigation dressing, characterized in that: the functional surgical irrigation dressing has the effects of rapid hemostasis, healing promotion, adhesion prevention, auxiliary repair and bacteriostasis, is suitable for various surgical irrigation, lavage and cleaning, is suitable for treating and repairing wound surfaces, mucous membranes and skin, can play a role in lubricating and isolating tissue wound surfaces, mucous membranes and skin and biological barrier, effectively prevents bleeding and has a bacteriostasis effect, and is also used as a slow-release carrier of a pharmaceutical preparation.
5. Use according to claim 4, characterized in that: the functional surgical irrigation dressing is used for directly irrigating or covering, smearing or wet dressing a wound after being infiltrated with a sterile dressing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211708385.8A CN115845127B (en) | 2022-12-29 | 2022-12-29 | Polysaccharide hemostatic repair biological glue solution and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211708385.8A CN115845127B (en) | 2022-12-29 | 2022-12-29 | Polysaccharide hemostatic repair biological glue solution and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115845127A CN115845127A (en) | 2023-03-28 |
| CN115845127B true CN115845127B (en) | 2023-11-24 |
Family
ID=85655908
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211708385.8A Active CN115845127B (en) | 2022-12-29 | 2022-12-29 | Polysaccharide hemostatic repair biological glue solution and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115845127B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6312725B1 (en) * | 1999-04-16 | 2001-11-06 | Cohesion Technologies, Inc. | Rapid gelling biocompatible polymer composition |
| ITMI20040989A1 (en) * | 2004-05-18 | 2004-08-18 | Gentium Spa | USE OF SULGLICOTIDE FOR THE TREATMENT OF MUCOSITES |
-
2022
- 2022-12-29 CN CN202211708385.8A patent/CN115845127B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 (3)
| Title |
|---|
| 体育院、系教材编审委员会.《运动生物化学》.人民教育出版社,1983,(第1版),第38页. * |
| 唐元升等.《人体医学参数与概念》.济南出版社,1995,(第1版),第165页. * |
| 硫酸糖肽的生物活性及药理作用;汤日玲等;《生命的化学》;第30卷(第2期);第246页左栏第1段至247页右栏第1段、第248页右栏第3-4段 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115845127A (en) | 2023-03-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8809301B2 (en) | Surgical hydrogel | |
| AU2007269406B2 (en) | Flexible bioresorbable hemostatic packing and stent | |
| HU226962B1 (en) | Biomaterials for preventing post-surgical adhesions comprised of hyaluronic acid derivatives | |
| PT85200B (en) | PROCESS FOR THE PREPARATION OF NEW AGLINIC ACID ESTERS | |
| CN109381738A (en) | A kind of chitosan-based hydrogel and its preparation method and application | |
| JP2003523237A (en) | Single phase gel for adhesion prevention | |
| US20130252921A1 (en) | Adhesion barrier containing hyaluronic acids and l-arginine | |
| KR101820306B1 (en) | Gallic Acid-Chitosan Complexes and Composition for Wound Healing Comprising Them | |
| CA2028709A1 (en) | Use of derivatives of chitin soluble in aqueous solutions for preventing adhesions | |
| EP3962546A1 (en) | A biocompatible, biodegradable and bioresorbable adhesion membrane including hyaluronic acid / chitosan / carboxymethyl cellulose and production method | |
| CN107519541B (en) | Hydrogel for preventing postoperative adhesion of abdominal cavity and preparation method and application thereof | |
| CN110787325A (en) | Disulfide bond cross-linked hyaluronic acid gel for preventing abdominal (pelvic) cavity postoperative tissue adhesion and preparation method thereof | |
| CN112121238A (en) | Multifunctional composite anti-adhesion material and preparation method thereof | |
| JP3796165B2 (en) | Anti-adhesive material | |
| CN111228296A (en) | Cross-linked hyaluronic acid ectoine isotonic wound flushing fluid | |
| CN105030667A (en) | Operation irrigating solution and preparation method thereof | |
| CN115845127B (en) | Polysaccharide hemostatic repair biological glue solution and preparation method and application thereof | |
| AU2021312621A1 (en) | Anti-adhesion polymer composition | |
| CN101028280B (en) | Lavage liquor preparation for operation and its production | |
| KR102103180B1 (en) | Anti-adhesion Composition Including Hyaluronic Acid Derivative, Pullulan and Carboxymethyl Cellulose and Manufacturing Method Thereof | |
| JP3420851B2 (en) | Anti-adhesion agent | |
| CN101077347A (en) | Multifunctional membrane used for glaucoma post-operation and preparation method thereof | |
| JPS6281319A (en) | High-viscosity preparation for medical use | |
| JP2003019194A (en) | Co-crosslinked gel composition comprising hyaluronic acid and carboxymethyl cellulose | |
| CN111378125B (en) | PEBP block polymer gel, preparation and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |