CN108498855B - Antibacterial hemostatic sol and preparation method thereof - Google Patents

Antibacterial hemostatic sol and preparation method thereof Download PDF

Info

Publication number
CN108498855B
CN108498855B CN201810439740.3A CN201810439740A CN108498855B CN 108498855 B CN108498855 B CN 108498855B CN 201810439740 A CN201810439740 A CN 201810439740A CN 108498855 B CN108498855 B CN 108498855B
Authority
CN
China
Prior art keywords
hemostatic
aqueous solution
sol
carboxymethyl chitosan
content
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
Application number
CN201810439740.3A
Other languages
Chinese (zh)
Other versions
CN108498855A (en
Inventor
黄剑东
唐凤翔
孙雅
高芳
谢伟
郑碧远
周宇阳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fuzhou University
Original Assignee
Fuzhou University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Fuzhou University filed Critical Fuzhou University
Priority to CN201810439740.3A priority Critical patent/CN108498855B/en
Publication of CN108498855A publication Critical patent/CN108498855A/en
Application granted granted Critical
Publication of CN108498855B publication Critical patent/CN108498855B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/008Hydrogels or hydrocolloids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0023Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061Use of materials characterised by their function or physical properties
    • A61L26/0066Medicaments; Biocides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/224Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials containing metals, e.g. porphyrins, vitamin B12
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/418Agents promoting blood coagulation, blood-clotting agents, embolising agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/04Materials for stopping bleeding

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Materials Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses an antibacterial hemostatic sol and a preparation method thereof, wherein the antibacterial hemostatic sol is prepared from sodium alginate, carboxymethyl chitosan quaternary ammonium salt, water-soluble phthalocyanine, glucose and water for injection. The antibacterial hemostatic sol has good hemostatic effect, also has the functions of wound irrigation and infection resistance, and is suitable for irregular wounds; and the problem that the traditional hemostatic materials (hemostatic gauze, hemostatic powder, hemostatic sponge and the like) have strong tissue adhesion and are easy to remove to cause secondary bleeding can be avoided, and the antibacterial effect can be further remarkable under indoor natural light irradiation, so that the problem of wound infection is deeply solved.

Description

Antibacterial hemostatic sol and preparation method thereof
Technical Field
The invention belongs to the technical field of antibacterial hemostatic materials, and particularly relates to an antibacterial hemostatic sol based on marine organism polysaccharide, and a preparation method and application thereof.
Background
Traumatic hemorrhage is one of common injuries in battlefields and various accident sites, and uncontrolled hemorrhage is the leading cause of death of wounded personnel in the scene. Even if the wounded can be sent to a hospital for rescue, massive blood loss before the hospital can cause higher death rate and complications (such as amputation) in the later period, so that the effective control on the bleeding of the wounded on the spot is significant. On the other hand, in various surgical operations, the reduction of bleeding and the shortening of the operation time play an important role in the prognosis of patients. The traditional hemostatic devices and hemostatic materials (veil and bandage) can not be used or have poor effect on a plurality of parts (such as chest, abdomen, head, neck and the like) of a human body, and have poor hemostatic effect on common field wounds and operation incisions with irregular shapes, depths, narrowness and the like. Although materials capable of absorbing and stopping bleeding, such as fibrin glue, gelatin sponge, oxidized cellulose, microfibrillar collagen, medical bioprotein glue, alginate fiber and the like, are clinically applied, the hemostatic materials also have a plurality of defects, mainly the hemostatic efficiency is still to be improved, and the hemostatic materials have single functions. Therefore, the development of a novel hemostatic material which has the advantages of difficult secondary trauma caused by dressing removal and the like and has the functions of rapid hemostasis, flushing, bacteriostasis and the like is a hotspot and a difficult point of the current research and development.
In situ gels are a class of gel materials that can be transformed from a liquid state to a semi-solid gel state at the site of application immediately after administration in a liquid state. The in-situ gel is used as an ideal biological scaffold, and can provide a proper microenvironment for cells and biomolecules due to similarity with a natural extracellular matrix, and the porous structure of the in-situ gel can effectively diffuse small molecules; in addition, it has excellent biocompatibility, biodegradability, small invasion force, applicability to various irregular wounds, and has attracted a great deal of attention as a moisture-rich three-dimensional matrix in hemostasis.
Sodium alginate is prepared fromβ-D-mannuronic acid (D-mannuronic acid)β-D-mannuonic, M) andαl-guluronic acid (1α-L-guluronic, G) is a water-soluble high molecular natural polysaccharide linked by (1 → 4) bonds, which dissolves rapidly in aqueous solutions or high humidity environments. the-COOH on the macromolecular chain of the sodium alginate reacts with NaCl in blood, so that the ionization balance of the blood can be broken and the blood coagulation factor can be activated; in the blood coagulation process, sodium alginate can absorb a large amount of water in blood, so that the concentration and viscosity of the blood are increased, the flow rate is reduced, and meanwhile, a viscid body formed by dissolving sodium alginate blocks the tail end of a capillary vessel and can be quickly adhered when meeting platelets, thereby achieving the effect of stopping bleeding. In addition, the sodium alginate also has high moisture retention, bacteriostasis and sterilization performance, and can be used as a medical dressing, the alginate medical dressing not only can absorb wound exudate, but also can form a gel film on the wound surface of a wound, thereby providing a proper moist physiological microenvironment for the wound surface healing, and simultaneously reducing the bacterial infection of the wound surface part.
Carboxymethyl chitosan is an amphoteric polysaccharide, exists in an aqueous solution in the form of ampholyte, contains amino groups capable of generating cations through protonation, and carboxyl groups capable of ionizing anions, and can increase the aggregation of red blood cells and the adhesion of platelets, thereby accelerating the hemostasis process and shortening the blood coagulation time. The cationic effect on the carboxymethyl chitosan quaternary ammonium salt can promote the erythrocyte aggregation, thereby playing a role in hemostasis; and the quaternary ammonium cation is also capable of inhibiting the growth of the microorganism by disrupting the cytoplasmic membrane of the microorganism. In addition, the carboxymethyl chitosan and the carboxymethyl chitosan quaternary ammonium salt have strong water absorption capacity and very good adhesion, and can be firmly pasted on a wound surface to fill the wound.
In addition, prevention of bacterial infection after hemostasis is also important for wound healing. A photosensitizer is a substance that absorbs photons to produce excited electrons, which in turn transfer excess energy to oxygen molecules, thereby initiating a series of photochemical reactions. Phthalocyanine, as a second generation photosensitizer, is an 18 pi compound with a high degree of conjugation-Planar aromatic macrocycles of electrons. In the aspect of antibiosis, the photosensitizer is firstly enriched in microbial cells and/or cell walls, and undergoes a photochemical reaction under the irradiation of light with a proper wavelength and the participation of oxygen to generate active oxygen, and the active oxygen causes oxidative damage to the cells in different modes to achieve the effect of bacteriostasis. In addition, the phthalocyanine has the advantages of low toxicity, high sterilization speed and capability of generating an antibacterial effect under indoor natural light irradiation.
In summary, the conventional solid hemostatic materials have strong tissue adhesion and good hemostatic effect, but have single function, cannot wash wounds, and are easy to cause secondary trauma when being removed. Although the liquid hemostatic material has the functions of flushing, is simple and convenient to operate, and is suitable for irregular wounds, the tissue adhesion strength is insufficient, and the hemostatic effect is not good. While in situ gels make up for some of the deficiencies of both solid and liquid hemostatic materials, they lose their flushing function when they transition from a liquid to a semi-solid gel. The hemostatic material simulates the formation mechanism of in-situ gel, and the hemostatic material is endowed with the flushing function by mixing the components and then converting the mixed components into sol with fluidity. And each macromolecular component (sodium alginate, carboxymethyl chitosan and carboxymethyl chitosan quaternary ammonium salt) in the sol has antibacterial activity, and a three-dimensional network structure is formed among the macromolecular components through hydrogen bonds and a small amount of ionic bonds, so that the problem of postoperative wound infection is solved. In addition, the phthalocyanine in the sol can further exert an antibacterial function under indoor natural light irradiation.
Disclosure of Invention
The invention provides an antibacterial hemostatic sol and a preparation method thereof, and aims to solve the problems that a liquid hemostatic material in the current market has poor hemostatic effect, a solid hemostatic material has single function and wound infection exists.
In order to achieve the purpose, the invention adopts the following technical scheme:
a photosensitive antibacterial hemostatic sol is prepared from sodium alginate, carboxymethyl chitosan quaternary ammonium salt, water-soluble phthalocyanine, glucose and water for injection; wherein the content of sodium alginate is 0.1-10g/L, the content of carboxymethyl chitosan is 0.5-50g/L, the content of carboxymethyl chitosan quaternary ammonium salt is 0-20g/L, the content of water-soluble phthalocyanine is 0-0.1g/L, and the content of glucose is 0-450 g/L.
The water-soluble phthalocyanine comprises phthalocyanine compounds and salts thereof, wherein the phthalocyanine compounds are connected with amino, carboxyl, sulfonic acid group, quaternary ammonium group, PEG chain and the like in a peripheral ring or axial direction.
The preparation method of the antibacterial hemostatic sol comprises the following steps:
1) respectively placing sodium alginate, carboxymethyl chitosan quaternary ammonium salt, water-soluble phthalocyanine and glucose into a closed automatic stirring container, adding water for injection, stirring at room temperature at a closed low speed (less than or equal to 600 rpm) for 1-2h to respectively obtain a sodium alginate aqueous solution, a carboxymethyl chitosan quaternary ammonium salt aqueous solution, a phthalocyanine aqueous solution and a glucose aqueous solution, and filtering and sterilizing by using a microporous filter membrane for later use;
2) mixing the obtained sodium alginate aqueous solution, carboxymethyl chitosan quaternary ammonium salt aqueous solution, phthalocyanine aqueous solution and glucose aqueous solution in a closed automatic stirring container according to a proportion, shaking and stirring at room temperature for 5-10min, and filling to obtain the antibacterial hemostatic sol.
The invention has the beneficial effects and outstanding advantages that:
1) the invention simulates the in-situ gel forming mechanism, and the prepared sol has the characteristic of convenient wound surface washing while ensuring good hemostasis effect, and is suitable for wound surface treatment which is difficult to operate and has irregular, deep, narrow shape and the like.
2) The invention keeps the molecular structures of the three polymers of sodium alginate, carboxymethyl chitosan and carboxymethyl chitosan quaternary ammonium salt through simple physical mixing, and simultaneously, the three polymers form a compact three-dimensional network structure through hydrogen bonds and a small amount of ionic bonds, thereby achieving the effects of well plugging the wound surface and assisting hemostasis. Meanwhile, because of a large number of hydrophilic groups contained in the product, the product has high hygroscopicity and can rapidly absorb blood in a wound surface.
3) Besides sodium alginate and chitosan derivatives with good antibacterial performance, phthalocyanine is embedded in the three-dimensional reticular gel structure of the sol, and the sol can play a better antibacterial effect under indoor natural light irradiation, so that wound infection is further effectively prevented.
Detailed Description
In order to make the present invention more comprehensible, the technical solutions of the present invention are further described below with reference to specific embodiments, but the present invention is not limited thereto.
Example 1
1) Respectively placing sodium alginate, carboxymethyl chitosan quaternary ammonium salt, zinc tetracarboxyphenoxyphthalocyanine and glucose into a closed automatic stirring container, adding water for injection, stirring at room temperature at a closed low speed (less than or equal to 600 rpm) for 1h to respectively obtain a sodium alginate aqueous solution with the content of 2.1g/L, a carboxymethyl chitosan aqueous solution with the content of 10.7g/L, a carboxymethyl chitosan quaternary ammonium salt aqueous solution with the content of 10.7g/L, a tetracarboxyphenoxyphthalocyanine aqueous solution with the content of 0.29g/L and a glucose aqueous solution with the content of 960g/L, and respectively filtering and sterilizing through a microporous filter membrane for later use;
2) mixing the obtained sodium alginate aqueous solution, carboxymethyl chitosan quaternary ammonium salt aqueous solution, tetra-carboxyphenoxy zinc phthalocyanine aqueous solution and glucose aqueous solution in a volume ratio of 20:30:10:1:3 in a closed automatic stirring container, stirring for 6min at room temperature in an oscillating way to ensure that the content of sodium alginate, carboxymethyl chitosan and tetra-carboxyphenoxy zinc phthalocyanine in the obtained sol are respectively 0.67g/L, 1.67 g/L, 0.0045g/L and 45g/L, and filling to obtain the antibacterial hemostatic sol.
Example 2
1) Respectively placing sodium alginate, carboxymethyl chitosan quaternary ammonium salt, 1- (4-aminoethyl phenoxy) zinc phthalocyanine and glucose into a closed automatic stirring container, adding water for injection, stirring at room temperature at a closed low speed (less than or equal to 600 rpm) for 2 hours to respectively obtain a sodium alginate aqueous solution with the content of 2.1g/L, a carboxymethyl chitosan aqueous solution with the content of 10.7g/L, a carboxymethyl chitosan quaternary ammonium salt aqueous solution with the content of 10.7g/L, a 1- (4-aminoethyl phenoxy) zinc phthalocyanine aqueous solution with the content of 0.45g/L and a glucose aqueous solution with the content of 960g/L, and respectively filtering and sterilizing through a microporous filter membrane for later use;
2) mixing the obtained sodium alginate aqueous solution, carboxymethyl chitosan quaternary ammonium salt aqueous solution, 1- (4-aminoethyl phenoxy) zinc phthalocyanine aqueous solution and glucose aqueous solution in a volume ratio of 20:30:10:1:3 in a closed automatic stirring container, stirring for 6min at room temperature in an oscillating way to ensure that the content of sodium alginate in the obtained sol is 0.67g/L, the content of carboxymethyl chitosan is 5g/L, the content of carboxymethyl chitosan quaternary ammonium salt is 1.67 g/L, the content of 1- (4-aminoethyl phenoxy) zinc phthalocyanine is 0.007g/L and the content of glucose is 45g/L, and filling to obtain the antibacterial hemostatic sol.
Example 3
1) Respectively placing sodium alginate, carboxymethyl chitosan quaternary ammonium salt, zinc tetracarboxyphenoxyphthalocyanine and glucose into a closed automatic stirring container, adding water for injection, stirring at room temperature at a closed low speed (less than or equal to 600 rpm) for 2 hours to respectively obtain a sodium alginate aqueous solution with the content of 2.2g/L, a carboxymethyl chitosan aqueous solution with the content of 10.8g/L, a carboxymethyl chitosan quaternary ammonium salt aqueous solution with the content of 10.8g/L, a tetracarboxyphenoxyphthalocyanine aqueous solution with the content of 0.43g/L and a glucose aqueous solution with the content of 968g/L, and respectively filtering and sterilizing through a microporous filter membrane for later use;
2) mixing the obtained sodium alginate aqueous solution, carboxymethyl chitosan quaternary ammonium salt aqueous solution, tetra-carboxyphenoxy zinc phthalocyanine aqueous solution and glucose aqueous solution in a volume ratio of 40:60:20:3:6 in a closed automatic stirring container, stirring for 6min at room temperature in an oscillating way to ensure that the content of sodium alginate, carboxymethyl chitosan and tetra-carboxyphenoxy zinc phthalocyanine in the obtained sol are respectively 0.67g/L, 1.67 g/L, 0.0068 g/L and 45g/L, and filling to obtain the antibacterial hemostatic sol.
Example 4
1) Respectively placing sodium alginate, carboxymethyl chitosan quaternary ammonium salt, 1- (4-aminoethyl phenoxy) zinc phthalocyanine and glucose into a closed automatic stirring container, adding water for injection, stirring at room temperature at a closed low speed (less than or equal to 600 rpm) for 2 hours to respectively obtain a sodium alginate aqueous solution with the content of 2.2g/L, a carboxymethyl chitosan aqueous solution with the content of 10.8g/L, a carboxymethyl chitosan quaternary ammonium salt aqueous solution with the content of 10.8g/L, a 1- (4-aminoethyl phenoxy) zinc phthalocyanine aqueous solution with the content of 0.67g/L and a glucose aqueous solution with the content of 968g/L, and respectively filtering and sterilizing through a microfiltration membrane for later use;
2) mixing the obtained sodium alginate aqueous solution, carboxymethyl chitosan quaternary ammonium salt aqueous solution, 1- (4-aminoethyl phenoxy) zinc phthalocyanine aqueous solution and glucose aqueous solution in a volume ratio of 40:60:20:3:6 in a closed automatic stirring container, oscillating and stirring for 6min at room temperature to ensure that the content of sodium alginate in the obtained sol is 0.67g/L, the content of carboxymethyl chitosan is 5g/L, the content of carboxymethyl chitosan quaternary ammonium salt is 1.67 g/L, the content of 1- (4-aminoethyl phenoxy) zinc phthalocyanine is 0.011 g/L and the content of glucose is 45g/L, and filling to obtain the antibacterial hemostatic sol.
Example 5
1) Respectively placing sodium alginate, carboxymethyl chitosan, zinc tetracarboxyphenoxyphthalocyanine and glucose into a closed automatic stirring container, adding water for injection, stirring at room temperature at a closed low speed (less than or equal to 600 rpm) for 2 hours to respectively obtain a sodium alginate aqueous solution with the content of 2.1g/L, a carboxymethyl chitosan aqueous solution with the content of 10.7g/L, a zinc tetracarboxyphenoxyphthalocyanine aqueous solution with the content of 0.29g/L and a glucose aqueous solution with the content of 960g/L, and respectively filtering and sterilizing through a microporous filter membrane for later use;
2) mixing the obtained sodium alginate aqueous solution, carboxymethyl chitosan aqueous solution, tetracarboxyphenoxy phthalocyanine zinc aqueous solution and glucose aqueous solution in a closed automatic stirring container according to the volume ratio of 30:30:1:3, stirring for 6min at room temperature in an oscillating way to ensure that the content of sodium alginate in the obtained sol is 1g/L, the content of carboxymethyl chitosan is 5g/L, the content of tetracarboxyphenoxy phthalocyanine zinc is 0.0045g/L and the content of glucose is 45g/L, and filling to obtain the antibacterial hemostatic sol.
Example 6 mouse tail wound hemostasis test
Experimental groups: the antibacterial hemostatic sol prepared in example 1.
Control group: control was performed with 0.9% physiological saline and a commercially available fluid hemostatic membrane of some brand.
The method comprises the following steps: the experimental healthy adult female mice totally have 18 mice, the weight is 25 +/-2 g, the experimental healthy adult female mice are randomly divided into a 0.9% physiological saline group, a commercially available fluid hemostatic membrane group and an antibacterial hemostatic sol group, and each group has 6 mice which are respectively numbered; chloral hydrate (7%) was used for intraperitoneal injection for anesthesia, and after anesthesia was successful, the mice were placed in a holder for tail-clipping experiments to compare the hemostatic time of three groups of mice. And (3) cutting the tail to be about 2cm in length, slightly pressing, immersing the tail of the bleeding into the sample solution to be detected, starting timing, and quickly replacing the solution every 10s until the timing is finished when the tail of the mouse stops bleeding. The time to start and stop hemostasis was recorded and the time to hemostasis was calculated and the results are shown in table 1.
TABLE 1 hemostasis time for mouse tail wound hemostasis experiment
Figure DEST_PATH_IMAGE002
As can be seen from table 1, the average hemostatic time of the commercially available fluid hemostatic membrane group is respectively shortened by about 25% compared with the 0.9% normal saline group, and the average hemostatic time of the antibacterial hemostatic sol group is shortened by about 50% compared with the commercially available fluid hemostatic membrane group, which is significantly different (P < 0.01), thus proving that the hemostatic effect of the antibacterial hemostatic sol provided by the present invention is better than that of the commercially available fluid hemostatic membrane.
Example 7 dorsal wound hemostasis test in rabbits
Experimental groups: the antibacterial hemostatic sol prepared in example 1.
Control group: control was performed with 0.9% physiological saline and a commercially available fluid hemostatic membrane of some brand.
The method comprises the following steps: 6 healthy adult female rabbits were used for the experiment, with a body weight of 2 + -0.2 kg. The experimental procedures of the control group and the experimental group were performed on the basis of one animal. The rabbit was injected slowly in the ear vein with fast sleep, and after anesthesia was successful, it was placed in a holder for wound hemostasis experiments to compare the hemostasis time of the three groups. The back of the animal is depilated and disinfected by 95 percent alcohol, 6 circular incisions are symmetrically cut along the two sides of the spinal column, the diameter is about 1.0cm, the depth reaches the skin circle layer, and then the circular incisions are carefully separated to the fascia layer to avoid the middle and large blood vessels of subcutaneous tissues. The bleeding was started under light pressure and recorded (the termination time was the time at which the wound stopped bleeding), and the bleeding around the wound was wiped with cotton every 10 seconds during the experiment for observation. The hemostatic procedures of six rabbits were the same, and the results are shown in table 2.
TABLE 2 comparison of hemostatic time in rabbit back trauma hemostatic experiments
Figure DEST_PATH_IMAGE004
As can be seen from Table 2, the mean hemostatic time for the commercially available fluid haemostatic membrane group was 22% shorter than the 0.9% saline group; the mean hemostatic time of the antibacterial hemostatic sol group was 68% shorter than that of the commercially available fluid hemostatic film group, with a significant difference (P < 0.01). It is fully proved that the hemostatic effect of the antibacterial hemostatic sol prepared by the invention is obviously superior to that of the fluid hemostatic film sold on the market.
Example 8 dorsal wound hemostasis test in rabbits
Experimental groups: the antibacterial hemostatic sol prepared in example 5.
Control group: control was performed with 0.9% physiological saline and a commercially available fluid hemostatic membrane of some brand.
The method comprises the following steps: 6 healthy adult female rabbits were used for the experiment, with a body weight of 2 + -0.2 kg. The experimental procedures of the control group and the experimental group were performed on the basis of one animal. The rabbit was injected slowly in the ear vein with fast sleep, and after anesthesia was successful, it was placed in a holder for wound hemostasis experiments to compare the hemostasis time of the three groups. The back of the animal is depilated and disinfected by 95 percent alcohol, 6 circular incisions are symmetrically cut along the two sides of the spinal column, the diameter is about 1.0cm, the depth reaches the skin circle layer, and then the circular incisions are carefully separated to the fascia layer to avoid the middle and large blood vessels of subcutaneous tissues. The bleeding was started under light pressure and recorded (the termination time was the time at which the wound stopped bleeding), and the bleeding around the wound was wiped with cotton every 10 seconds during the experiment for observation. The hemostatic procedures of six rabbits were the same, and the results are shown in table 3.
TABLE 3 comparison of hemostatic time in rabbit back trauma hemostatic experiments
Figure DEST_PATH_IMAGE006
As can be seen from Table 3, the mean hemostatic time for the commercially available fluid haemostatic membrane group was 22% shorter than the 0.9% saline group; the mean hemostatic time of the antibacterial hemostatic sol group was 68% shorter than that of the commercially available fluid hemostatic film group, with a significant difference (P < 0.01). It is fully proved that the hemostatic effect of the antibacterial hemostatic sol prepared by the invention is obviously superior to that of the fluid hemostatic film sold on the market.
Example 9 antibacterial experiments
Experimental groups: the antibacterial hemostatic sols (antibacterial hemostatic sol group (plus phthalocyanine)) prepared in examples 1-4.
Control group: PBS buffer solution, pure phthalocyanine with different concentrations, carboxymethyl chitosan without phthalocyanine, carboxymethyl chitosan quaternary ammonium salt and sodium alginate blended sol (sol group (without phthalocyanine)) are respectively used as control groups.
The experimental group and the control group are required to be subjected to phototoxicity and dark toxicity experiments.
The method comprises the following steps: selecting staphylococcus aureus colony with proper size from activated Luria-Bertain high-salt culture medium, adding a proper amount of PBS, performing ultrasonic treatment for 5min to obtain uniform bacterial suspension, placing a small amount of bacterial suspension in a blood counting chamber, and making the bacterial suspension in the blood counting chamberThe concentration is controlled at 2-5 × 106CFU/mL. Adding the prepared bacterial suspension into a sterile 96-well plate in a way of 100 mu L per well, then adding the freshly prepared sample solution to be detected into a corresponding well plate, so that the volume of the sample solution to be detected is 100 mu L per well, and uniformly blowing by using a pipette. The prepared drug sensitive plate is placed in an incubator at 37 ℃ and is cultured for 6 hours in the dark, so that the bacteria can fully absorb and adsorb the drugs, and then the bacteriostasis rate under the dark condition is measured. Preparing phototoxic drug sensitive plate with red light (15 mW/cm) of 610nm or more2) Irradiating for 30min, and measuring the bacteriostasis rate under the illumination condition. The results are shown in Table 4. Each set of experiments was repeated at least three times.
The method for calculating the bacteriostasis rate comprises the following steps: bacteriostasis rate =100% × (1-average number of colonies in experimental group/average number of colonies in control group)
TABLE 4 bacteriostasis rates against Staphylococcus aureus
Figure DEST_PATH_IMAGE008
As can be seen from Table 4, the sol group without phthalocyanine has a certain bacteriostatic effect, but the bacteriostatic ability of the antibacterial hemostatic sol added with phthalocyanine is obviously improved after illumination and is higher than that of the antibacterial hemostatic sol under pure phthalocyanine illumination.
The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the present invention.

Claims (2)

1. An antibacterial hemostatic sol, which is characterized in that: the antibacterial hemostatic sol is prepared from sodium alginate, carboxymethyl chitosan quaternary ammonium salt, water-soluble phthalocyanine, glucose and water for injection; wherein the content of sodium alginate is 0.1-10g/L, the content of carboxymethyl chitosan is 0.5-50g/L, the content of carboxymethyl chitosan quaternary ammonium salt is 0-20g/L, the content of water-soluble phthalocyanine is 0-0.1g/L, and the content of glucose is 0-450 g/L;
wherein the water-soluble phthalocyanine is tetracarboxyphenoxy phthalocyanine zinc or 1- (4-aminoethyl phenoxy) phthalocyanine zinc;
the preparation method of the antibacterial hemostatic sol comprises the following steps:
1) respectively adding water for injection into sodium alginate, carboxymethyl chitosan quaternary ammonium salt, water-soluble phthalocyanine and glucose, stirring at room temperature under sealed condition at low speed for 1-2h to obtain sodium alginate aqueous solution, carboxymethyl chitosan quaternary ammonium salt aqueous solution, phthalocyanine aqueous solution and glucose aqueous solution, and filtering with microporous filter membrane for sterilization;
2) mixing the obtained sodium alginate aqueous solution, carboxymethyl chitosan quaternary ammonium salt aqueous solution, phthalocyanine aqueous solution and glucose aqueous solution in a closed automatic stirring container according to a proportion, shaking and stirring at room temperature for 5-10min, and then filling to obtain the antibacterial hemostatic sol.
2. The antibacterial hemostatic sol of claim 1, wherein: the rotating speed of the low-speed stirring in the step 1) is less than or equal to 600 rpm.
CN201810439740.3A 2018-05-09 2018-05-09 Antibacterial hemostatic sol and preparation method thereof Active CN108498855B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810439740.3A CN108498855B (en) 2018-05-09 2018-05-09 Antibacterial hemostatic sol and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810439740.3A CN108498855B (en) 2018-05-09 2018-05-09 Antibacterial hemostatic sol and preparation method thereof

Publications (2)

Publication Number Publication Date
CN108498855A CN108498855A (en) 2018-09-07
CN108498855B true CN108498855B (en) 2021-04-27

Family

ID=63400129

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810439740.3A Active CN108498855B (en) 2018-05-09 2018-05-09 Antibacterial hemostatic sol and preparation method thereof

Country Status (1)

Country Link
CN (1) CN108498855B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109680498A (en) * 2019-01-11 2019-04-26 深圳市科能医疗器械有限公司 A kind of medical preparation method for resisting antibacterial gauze of nanometer-level silver ion
CN111533827B (en) * 2020-06-15 2021-04-02 北京化工大学 Electronegative polysaccharide quaternary ammonium salt hemostatic material and preparation method and application thereof
CN113855844B (en) * 2021-09-18 2022-08-12 军事科学院军事医学研究院环境医学与作业医学研究所 Antibacterial material and preparation method and application thereof
CN115591008A (en) * 2021-12-31 2023-01-13 上海炫鑫医药科技有限公司(Cn) Spray-type liquid wound-protecting dressing and preparation method thereof

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3753581B2 (en) * 1999-05-20 2006-03-08 花王株式会社 Absorbent articles
ES2244793T3 (en) * 2001-03-21 2005-12-16 L. MOLTENI &amp; C. DEI FRATELLI ALITTI SOCIETA' DI ESERCIZIO SOCIETA' PER AZIONI NON CENTROSIMETRIC ANALOGS OF PHTALOCIANINE REPLACED BY METALS, ITS PREPARATION AND ITS USE IN PHOTODYNAMIC THERAPY AND IN VIVO DIAGNOSIS.
CN1256946C (en) * 2004-07-15 2006-05-24 福州大学 Novel method for preparing anticancer photosensitizer of amphiphilic phthalocyanine and its application
CA2607912A1 (en) * 2005-05-13 2006-11-16 Netech Inc. Medical composition for promotion of skin regeneration
CN1939919B (en) * 2005-09-30 2010-06-09 中国科学院福建物质结构研究所 Low-toxic and broad-spectrum phthalocyanine bactericide, its production and use
CN101879795B (en) * 2010-06-08 2012-11-07 黑龙江大学 Phthalocyanine/TiO2 ordered film and preparation method thereof
US20120070401A1 (en) * 2010-09-21 2012-03-22 Jinzhong Zhang Composition and Method for Promoting Wound Healing
KR101265257B1 (en) * 2010-12-23 2013-05-16 한국수력원자력 주식회사 Hydrogels for wound or ulcer dressings comprising enzymes and preparation method thereof
CN102847193B (en) * 2012-07-04 2015-04-29 杭州科洛生物技术有限公司 Chitosan fluid dressing film
CN105381500A (en) * 2015-11-23 2016-03-09 华中师范大学 Functional wound surface repairing material and preparation method thereof
CN105622682B (en) * 2016-03-10 2018-10-30 福州大学 A kind of carboxyl zinc phthalocyanine-adriamycin conjugate and its preparation and application
CN106039394A (en) * 2016-06-02 2016-10-26 四川奎星医用高分子制品有限责任公司 Medical composite chitosan gel containing antibacterial drug
CN105999358A (en) * 2016-07-20 2016-10-12 广东泰宝医疗科技股份有限公司 Method for preparing slow-release antibacterial dressing
CN106620695B (en) * 2016-08-30 2021-06-29 郑州嘉泰生物科技有限公司 Photosensitive medicinal preparation for photodynamic sterilization and application thereof

Also Published As

Publication number Publication date
CN108498855A (en) 2018-09-07

Similar Documents

Publication Publication Date Title
CN108498855B (en) Antibacterial hemostatic sol and preparation method thereof
JP2617260B2 (en) Gel composition for wound treatment
CN103083713B (en) A kind of aseptic polymerization wound-surface cover dressing
CN1320931C (en) Dressing material containing medicine chitoholosida and its preparation method
CN103041438B (en) Moist antibacterial hydrogel dressing for curing diabetic foot ulcer
CN108187120B (en) Anesthesia department medical pain-relieving and bleeding-stopping dressing and preparation method thereof
CN101121041A (en) Denaturated starch absorbable hemostatic material and preparation method thereof
CN104623718B (en) Chitosan petrolatum gauze and preparation method thereof
CN108853570B (en) Hemostatic sponge and preparation method thereof
CN105056285B (en) It is a kind of can adhesion organization crack growth factor combine dressing and preparation method thereof
CN103848926B (en) A kind of preparation method of using carboxyl chitosan and purposes
CN103755965A (en) Polylysine hydrogel and preparation method and application thereof
CN100387238C (en) Medical hemostasis anti-adhesive irrigation solution
WO2015103988A1 (en) Medical dressing hydrogel composite fabric, and preparation method therefor and uses thereof
JP2752782B2 (en) Soluble hemostatic fabric
CN101597381A (en) A kind of calcium alginate composite membrane medical dressing of pasting behind the pin and its production and application that is used for
CN109453411A (en) A kind of chitosan dressing
CN107033397A (en) A kind of preparation method of calcium chelant carboxyl chitosan/organo montmorillonite gel rubber material
JP4486304B2 (en) Microbial cellulosic wound dressings for the treatment of chronic wounds
CN112870430A (en) Composite gel hemostatic powder based on natural polysaccharide, and preparation method and application thereof
WO2011100935A1 (en) Dry material of hydrogel for wound dressing and its method of preparation
CN107049930A (en) A kind of promoting healing wound gel and preparation method thereof
CN116712389A (en) Biological polysaccharide hemostatic flushing glue solution, preparation method and application
CN106822986B (en) A kind of preparation method of the porous ball hemostatic material of chitosan-agar oligosaccharide
CN113018505B (en) Preparation method of sodium alginate nano-silver antibacterial hydrogel dressing

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