Metakaolin based hemostatic sponge material and preparation method thereofTechnical Field
The invention belongs to the technical field of hemostatic materials, and particularly relates to a metakaolin-based hemostatic sponge material and a preparation method thereof.
Background
Uncontrolled bleeding is a major cause of death in injuries, natural disasters and various daily accidents. Early control of bleeding becomes the best strategy to reduce patient mortality. Chitosan has the characteristics of good biocompatibility, biodegradability, hemostasis, wound healing promotion and the like, so that chitosan hemostatic materials are hot spots of domestic and foreign research. The existing pure chitosan hemostatic material has the problems of poor toughness and unobvious hemostatic effect. The composite fiber hemostatic material can be compounded with other materials or medicines to improve toughness and shorten hemostasis time, for example, in the preparation research of novel war wound emergency dressing (medical and health equipment, 2007,28(9):1-3.) of the concerned et al, the hemostasis time of the chitosan and calcium alginate composite fiber hemostatic material is reported to be 127.8+33.6s (wounds of 2cm multiplied by 2cm on two sides of the back of a rabbit); the average hemostasis time of the chitosan and traditional Chinese medicine (pseudo-ginseng or bletilla striata) composite hemostasis material disclosed by application number 200610048015.0 and invention name 'a novel efficient traditional Chinese medicine/chitosan composite hemostasis material' is 165-177 s (compressing and hemostasis of inner artery of femoral part of mouse).
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a metakaolin-based hemostatic sponge material and a preparation method thereof. The metakaolin based hemostatic sponge material provided by the invention can quickly absorb bleeding and has a good hemostatic effect.
The technical scheme provided by the invention is as follows:
a preparation method of a metakaolin-based hemostatic sponge material comprises the following steps:
1) preparing a mixed solution of chitosan and acetic acid; preparing an aqueous solution of carboxymethyl chitosan; preparing an aqueous solution of glycerol; preparing a metakaolin hydrochloric acid suspension;
2) uniformly mixing the mixed solution of chitosan and acetic acid prepared in the step 1), the aqueous solution of carboxymethyl chitosan and the aqueous solution of glycerol to obtain a first mixed solution;
3) adding the metakaolin acidic suspension into the first mixed solution obtained in the step 2) under the stirring condition to obtain a second mixed solution;
4) pouring the second mixed solution obtained in the step 3) into a mold, and then placing the mold into a vacuum freeze dryer for freeze drying to obtain the metakaolin-based hemostatic sponge material;
wherein:
in the step 1), in the mixed solution of chitosan and acetic acid, the weight percentage of chitosan is 3-5%, and the weight percentage of acetic acid is 1-2%; in the aqueous solution of the carboxymethyl chitosan, the weight percentage of the carboxymethyl chitosan is 3-6%; in the aqueous solution of the glycerol, the weight percentage of the glycerol is 5-10%; in the metakaolin hydrochloric acid suspension, the weight percentage of metakaolin is 3-5%, the weight percentage of hydrochloric acid is 5-9%, and the weight percentage of a dispersing agent is 0.2-0.5%;
in the step 2) and the step 3), according to parts by weight, the use amount of the mixed solution of chitosan and acetic acid is 45-55 parts, the use amount of the aqueous solution of carboxymethyl chitosan is 12-14 parts, the use amount of the aqueous solution of glycerol is 30-38 parts, and the use amount of the metakaolin hydrochloric acid suspension is 20-25 parts;
in the step 4), the temperature of freeze drying is-30 to-50 ℃, and the time of freeze drying is 24 to 48 hours.
The metakaolin-based hemostatic sponge material can be prepared by the preparation method, can rapidly absorb bleeding, and has a good hemostatic effect.
Specifically, in the step 2): uniformly mixing the mixed solution of chitosan and acetic acid, the aqueous solution of carboxymethyl chitosan, the aqueous solution of glycerol and the adjuvant prepared in the step 1) to obtain a first mixed solution, wherein the dosage of the adjuvant is 0.5-3 parts by weight.
Preferably, the adjuvant is a hemostatic drug and/or an antibacterial drug.
Preferably, the hemostatic drug is etamsylate; the antibacterial agent is mupirocin.
Specifically, the dispersant is sodium acrylate or sodium hexametaphosphate.
Further, in the step 3), after the second mixed solution is obtained, continuously stirring for 2-4 hours.
Specifically, the stirring speed of the continuous stirring is 60-120 revolutions per minute.
The invention also provides the metakaolin based hemostatic sponge material prepared by the preparation method of the metakaolin based hemostatic sponge material.
The metakaolin based hemostatic sponge material prepared by the invention has a quick hemostatic effect, and can be used for hemostasis in clinical operations and promotion of wound healing. The preparation method is simple and convenient to operate.
Detailed Description
The principles and features of this invention are described below in conjunction with examples which are set forth to illustrate, but are not to be construed to limit the scope of the invention.
Example 1
The preparation method of the metakaolin based hemostatic sponge material comprises the following steps:
1) preparing a mixed solution of chitosan and acetic acid, wherein the weight percentage of the chitosan is 5% and the weight percentage of the acetic acid is 1%;
preparing an aqueous solution of carboxymethyl chitosan, wherein the weight percentage of the carboxymethyl chitosan in the aqueous solution of carboxymethyl chitosan is 6%;
preparing a glycerol aqueous solution, wherein the weight percentage of glycerol in the glycerol aqueous solution is 5%;
preparing a metakaolin hydrochloric acid suspension, wherein the metakaolin hydrochloric acid suspension comprises 5 wt% of metakaolin, 5 wt% of hydrochloric acid and 0.5 wt% of sodium acrylate or sodium hexametaphosphate serving as a dispersing agent;
2) uniformly mixing 45 parts of the mixed solution of chitosan and acetic acid prepared in the step 1), 14 parts of aqueous solution of carboxymethyl chitosan, 30 parts of aqueous solution of glycerol, 1 part of etamsylate and 1 part of mupirocin to obtain a first mixed solution;
3) adding 20 parts of metakaolin acidic suspension into the first mixed solution obtained in the step 2) under the stirring condition to obtain a second mixed solution, and continuously stirring for 4 hours at the stirring speed of 60 revolutions per minute;
4) pouring the second mixed solution obtained in the step 3) into a mould, and then placing the mould into a vacuum freeze dryer for freeze drying to obtain the metakaolin-based hemostatic sponge material 1, wherein the freeze drying temperature is-50 ℃, and the freeze drying time is 24 hours.
Example 2
The preparation method of the metakaolin based hemostatic sponge material comprises the following steps:
1) preparing a mixed solution of chitosan and acetic acid, wherein the weight percentage of the chitosan is 3% and the weight percentage of the acetic acid is 2% in the mixed solution of the chitosan and the acetic acid;
preparing an aqueous solution of carboxymethyl chitosan, wherein the weight percentage of the carboxymethyl chitosan in the aqueous solution of carboxymethyl chitosan is 3%;
preparing a glycerol aqueous solution, wherein the weight percentage of glycerol in the glycerol aqueous solution is 10%;
preparing metakaolin hydrochloric acid suspension, wherein the metakaolin hydrochloric acid suspension comprises 3 wt% of metakaolin, 9 wt% of hydrochloric acid and 0.2 wt% of sodium acrylate or sodium hexametaphosphate serving as a dispersing agent;
2) uniformly mixing 55 parts of the mixed solution of chitosan and acetic acid prepared in the step 1), 12 parts of aqueous solution of carboxymethyl chitosan, 38 parts of aqueous solution of glycerol, 1 part of etamsylate and 1 part of mupirocin to obtain a first mixed solution;
3) adding 25 parts of metakaolin acidic suspension into the first mixed solution obtained in the step 2) under the stirring condition to obtain a second mixed solution, and continuously stirring for 2 hours at the stirring speed of 120 revolutions per minute;
4) pouring the second mixed solution obtained in the step 3) into a mould, and then placing the mould into a vacuum freeze dryer for freeze drying to obtain the metakaolin-based hemostatic sponge material 2, wherein the freeze drying temperature is-30 ℃, and the freeze drying time is 48 hours.
Example 3
The preparation method of the metakaolin based hemostatic sponge material comprises the following steps:
1) preparing a mixed solution of chitosan and acetic acid, wherein the weight percentage of the chitosan is 4% and the weight percentage of the acetic acid is 1.5%;
preparing an aqueous solution of carboxymethyl chitosan, wherein the weight percentage of the carboxymethyl chitosan in the aqueous solution of carboxymethyl chitosan is 4.5%;
preparing a glycerol aqueous solution, wherein the weight percentage of glycerol in the glycerol aqueous solution is 7%;
preparing metakaolin hydrochloric acid suspension, wherein in the metakaolin hydrochloric acid suspension, the weight percentage content of metakaolin is 4%, the weight percentage content of hydrochloric acid is 7%, and the weight percentage content of dispersant sodium acrylate or sodium hexametaphosphate is 0.3%;
2) uniformly mixing 40 parts of the mixed solution of chitosan and acetic acid prepared in the step 1), 13 parts of aqueous solution of carboxymethyl chitosan, 35 parts of aqueous solution of glycerol, 1 part of etamsylate and 1 part of mupirocin to obtain a first mixed solution;
3) adding 22 parts of metakaolin acidic suspension into the first mixed solution obtained in the step 2) under the stirring condition to obtain a second mixed solution, and continuously stirring for 3 hours at the stirring speed of 90 revolutions per minute;
4) pouring the second mixed solution obtained in the step 3) into a mould, and then placing the mould into a vacuum freeze dryer for freeze drying to obtain the metakaolin-based hemostatic sponge material 3, wherein the freeze drying temperature is-40 ℃, and the freeze drying time is 36 hours.
Comparative example 1
The preparation method of the metakaolin based hemostatic sponge material comprises the following steps:
1) preparing a mixed solution of chitosan and acetic acid, wherein the weight percentage of the chitosan is 4% and the weight percentage of the acetic acid is 1.5%;
preparing an aqueous solution of carboxymethyl chitosan, wherein the weight percentage of the carboxymethyl chitosan in the aqueous solution of carboxymethyl chitosan is 4.5%;
preparing a glycerol aqueous solution, wherein the weight percentage of glycerol in the glycerol aqueous solution is 7%;
2) uniformly mixing 40 parts of the mixed solution of chitosan and acetic acid prepared in the step 1), 13 parts of aqueous solution of carboxymethyl chitosan, 35 parts of aqueous solution of glycerol, 1 part of etamsylate and 1 part of mupirocin to obtain a first mixed solution;
3) pouring the first mixed solution obtained in the step 2) into a mould, and then placing the mould into a vacuum freeze dryer for freeze drying to obtain the metakaolin-based hemostatic sponge material, wherein the freeze drying temperature is-40 ℃, and the freeze drying time is 36 hours.
The hemostatic effect of the metakaolin-based hemostatic sponge material 3 of the present invention was verified by the following tests
1. Blood volume test of metakaolin based hemostatic sponge material 3:
the metakaolin based hemostatic sponge material 3 prepared by the embodiment with the diameter of 3mm multiplied by 3mm is soaked in the blood of a fresh rabbit for 10min and then taken out, and the calculation is carried out according to the formula 1: the blood absorption amount of the metakaolin based hemostatic sponge material 3 per gram is 7.7+1.5 g.
2. Animal wound hemostasis experiment:
materials: the metakaolin-based hemostatic sponge material 3 prepared by the embodiment, a new zealand big rabbit, a surgical blade, a pair of sterilizing scissors and a stopwatch.
Experimental method 1 (rabbit auricular dorsal artery hemostasis experiment):
1) taking about 2.5kg of New Zealand big rabbits, randomly grouping, and performing intraperitoneal injection of 10% chloral hydrate for anesthesia after the ears of the rabbits are unhaired;
2) using a surgical blade to cut off an artery on the back plane of the ear;
3) the rapid hemostatic sponge prepared by the embodiment is made into a square with the diameter of 1.5mm multiplied by 1.5mm, and the square is covered on a wound and pressed; until the hemostatic sponge is uncovered and no wound bleeds again, the blood is successful, and the hemostatic time of the rapid hemostatic sponge is recorded;
4) attention is paid to observe the abnormal performance and postoperative recovery condition of the rabbits in the experimental process.
Experimental method 2 (rabbit popliteal artery hemostasis experiment):
1) after hair is removed from the hind legs of the rabbits, the rabbits are anesthetized, and 10% chloral hydrate is injected into the abdominal cavity for anesthesia;
2) the metakaolin-based hemostatic sponge material 3 prepared in the embodiment is cut into a square shape of 3mm × 3 mm;
3) cutting open the skin of the rabbit thigh by using a scalpel, cutting off muscles and the popliteal artery of the rabbit, and filling the hemostatic sponge in the step (2) at the artery fracture and pressing; until the hemostatic sponge is uncovered and no wound bleeds again, the blood is successful, and the hemostatic time of the quick hemostatic sponge under the above conditions is recorded;
4) attention is paid to observe the abnormal performance and postoperative recovery condition of the rabbits in the experimental process.
Experimental method 3 (comparative experiment):
the hemostatic sponges in experimental method 1 and experimental method 2 were replaced with metakaolin-based hemostatic sponge material 4, and the hemostatic effect was observed. The hemostatic properties of the different hemostatic materials were evaluated by hemostatic time, survival rate, wound recovery, etc., and the results are shown in table 1.
TABLE 1
| Hemostatic material | Wound site | Hemostasis time(s) | Survival rate | Wound healing |
| Example 3 materials | Ear back artery | 35±7 | 100％ | Good effect |
| Comparative example 1 Material | Ear back artery | 50±10 | 100％ | Good effect |
| Example 3 materials | Popliteal artery | 215±18 | 100％ | Good effect |
| Comparative example 1 Material | Popliteal artery | 280±30 | 100％ | Good effect |
From the results in table 1, it can be seen that for the rabbit auricular dorsal artery hemorrhage model, the proportion of the metakaolin-based hemostatic sponge material prepared by the invention is reduced by 30%; for a popliteal artery hemostasis model of a rabbit, the metakaolin-based hemostasis sponge material prepared by the invention can realize hemostasis within 4min, and the survival of organisms after hemostasis is ensured.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.