CN107320761B

CN107320761B - Efficient hemostatic dressing containing high-water-absorption core-spun powder balls and preparation method thereof

Info

Publication number: CN107320761B
Application number: CN201710580661.XA
Authority: CN
Inventors: 孙宾; 朱美芳; 秦荣基; 葛星; 李敬
Original assignee: Shandong Luhai Lansheng Biotechnology Co ltd; Donghua University
Current assignee: Shandong Luhai Lansheng Biotechnology Co ltd; Donghua University
Priority date: 2017-07-17
Filing date: 2017-07-17
Publication date: 2020-05-05
Anticipated expiration: 2037-07-17
Also published as: CN107320761A

Abstract

The invention provides a high-efficiency hemostatic dressing containing a high-water-absorption core-spun powder ball and a preparation method thereof, and the technical scheme is as follows: the base material is a mesh sponge with pores, the base material contains high water absorption sites, and the high water absorption sites of the base material are uniformly distributed and fixed in the sponge. The efficient hemostasis system mainly comprises an adsorption layer and a wrapping layer, the wrapping layer is wrapped inside the sponge, the surface of the wrapping layer contains a weak water-absorbing material, the inner layer of the wrapping layer contains a super water-absorbing material, and the wrapping layer forms a super water-absorbing powder mass area inside the sponge. The content of the super-absorbent powder balls in the high-efficiency hemostatic sponge is 0.1-1 wt%, the water absorption rate is 60-120 times, and the porosity of the base material is more than 95%. The invention has the beneficial effects that: the high-efficiency hemostatic dressing prepared by the invention has the advantages of high water absorption rate, high water absorption multiple and the like, can realize rapid hemostasis aiming at the condition of massive bleeding, and is soft, elastic and easy to attach on the surface, thereby being beneficial to wound healing.

Description

Efficient hemostatic dressing containing high-water-absorption core-spun powder balls and preparation method thereof

Technical Field

The invention relates to the technical field of hemostatic dressings, in particular to a high-efficiency hemostatic dressing containing a high-water-absorption core-spun powder ball and a preparation method thereof.

Background

Whether hemostasis can be achieved timely and effectively is a critical factor for medical dressings. At present, the local hemostatic materials which are more clinically applied are mainly collagen hemostatic agents (such as gelatin sponge), oxidized cellulose (such as instant yarn) and the like. However, these materials have various problems, such as the gelatin collagen material is apt to increase the infection rate of the wound, and the adhesiveness is poor, and the material is apt to be peeled off. The oxidized cellulose fiber is loose, easy to cause rebleeding, long in hemostasis time and poor in theory and practice of the effect on high and medium bleeding, so that the application is limited. Therefore, the research on a novel high-efficiency hemostatic dressing with good biocompatibility has important practical significance. The chitosan has good biocompatibility and biodegradability and natural physiological functions of antibiosis, antiphlogosis, hemostasis, healing promotion and the like, and is an excellent medical dressing raw material. The chitosan hemostatic material aggregates red blood cells with anions in blood together through the adsorption of anions and cations to form a blood clot; and the chitosan can obviously promote the adhesion and aggregation of the blood platelets, and simultaneously forms a hemostatic gel protective film with blood to plug wounds, thereby coagulating the blood. However, pure carboxymethyl chitosan sponge has poor water resistance, poor mechanical stability, and low water absorption rate and water absorption capacity, so that the performance defects of the carboxymethyl chitosan sponge need to be improved by a composite modification method.

Disclosure of Invention

The invention provides a high-efficiency hemostatic dressing containing a high-water-absorption core-spun powder dough and a preparation method thereof through years of practice, and the innovative system is as follows: a, a super absorbent material coating system: compared with the traditional method of directly dissolving and directly dispersing the super absorbent resin on a solution carrier and the method of sponge surface coating post-treatment, the method provides a new dispersing thought, and a series of related carriers/dispersing systems with different functions can be designed according to the difference of the components and the properties of the added super absorbent particles; b, dough embedding system: designing a water mist particle embedded solution system, wherein the water mist particle is a material containing super water absorbability, and uniformly dispersing the material into a carboxymethyl chitosan solution system before gelation; c, a hemostatic mechanism of the carboxymethyl chitosan sponge: the carboxymethyl chitosan is prepared by carboxymethyl of chitosan, which greatly improves water solubility, solves the problem of stimulation to human body caused by the fact that the chitosan is only dissolved in acidic condition, and retains the excellent performance of the chitosan, thus the carboxymethyl chitosan attracts attention in the field of medicine. Meanwhile, the carboxymethyl chitosan has natural good antibacterial property and the effects of regulating blood coagulation and the like. The carboxymethyl chitosan gathers the red blood cells with anions together through the adsorption of anions and cations to form a blood clot, and the blood is coagulated; secondly, the carboxymethyl chitosan can obviously promote the adhesion and aggregation of the blood platelets, thereby coagulating the blood. The carboxymethyl chitosan is prepared into the sponge dressing by a freeze drying method, and the porous structure can greatly increase the adsorption capacity of blood and better exert the hemostatic effect. The hemostatic sponge is blended and crosslinked with carboxymethyl starch and the like to prepare the composite sponge, so that the hemostatic sponge not only has the function of remarkably improving the hemostatic quantity, but also can enable the interior of the sponge to be constructed into a stable three-dimensional structure so as to strengthen the mechanical property of the sponge; wetting wound theory: according to the moist wound theory, the wound is accelerated to heal in a moist environment, so that a good hemostatic effect is achieved. In a wet environment, the wound healing rate is 2 times faster than in a dry environment. By "moist environment" is not meant a "moist healing environment" and excess exudate can cause overgrowth of granulation tissue and maceration of the skin surrounding the wound. True "wet wound healing" refers to the local wetting of a wound without the formation of scabs. Under the premise, if a wet healing environment close to a physiological state is created during nursing, the granulation growth is facilitated, and the skin cell division is facilitated. However, the environment is created, and meanwhile, the dressing is ensured not to be adhered to the new granulation tissue of the wound, no secondary injury is caused when the dressing is replaced, no pain is caused, and the wound is promoted to heal quickly. This practice of creating a moist healing environment is known as a "wound treatment"; the water absorption mechanism of the super (super) absorbent resin is as follows: a super (superabsorbent) resin is an ion-exchange resin, generally in the form of particles, each of which is composed of three parts: a crosslinked network backbone having three dimensions; a plurality of functional groups attached to the backbone; the functional group is adsorbed with exchangeable ions. Whether the super (super) absorbent resin can absorb water which is hundreds times or even thousands times higher than the self weight. The reason is as follows: the molecule of the compound has strong hydrophilic groups, such as carboxyl, hydroxyl and the like; the resin has a cross-linked structure, which makes it insoluble when interacting with water; the interior of the system has high-concentration ionic groups, so that high osmotic pressure pointing to the interior of the system is formed inside and outside the system, water in the environment has a tendency of diffusing towards the interior of the volume, and the improvement of water absorption capacity is ensured; has high molecular weight, and the increased molecular weight can increase the mechanical strength after high water absorption and improve the water absorption capacity.

The purpose of the invention is realized by the following technical scheme: the dressing comprises the following raw material components: carboxymethyl chitosan, carboxymethyl starch (high performance), sodium alginate, a cross-linking agent (glutaraldehyde, sodium trimetaphosphate or calcium chloride), and the like. The base material used in the invention is a reticular sponge with a porous structure, and the base material contains high water absorption sites which are uniformly distributed and fixed in the sponge. The efficient hemostasis system mainly comprises an adsorption layer, a sponge and a wrapping layer, wherein the wrapping layer is wrapped inside the sponge and mainly comprises a surface layer and an inner layer, the surface layer contains a weak water-absorbing material, the inner layer contains a super water-absorbing material, and the inner layer of the wrapping layer is formed with a super water-absorbing powder ball area. The skin-friendly sponge base material is carboxymethyl chitosan or carboxymethyl starch or other materials, the super water-absorbing powder groups are super water-absorbing resin or other materials, and the water-absorbing swelling material is carboxymethyl chitosan or sodium alginate or other materials. The content of the super-absorbent powder balls in the high-efficiency hemostatic sponge is 0.1-1 wt%, the water absorption rate is 60-120 times, and the porosity of the base material is more than 95%.

The skin-friendly sponge base material has good biocompatibility, and the prepared sponge is flexible and easy to attach; the efficient hemostasis system mainly comprises an adsorption layer and a wrapping layer, wherein the wrapping layer is wrapped inside the sponge, the surface of the wrapping layer contains a weak water-absorbing material, the inner layer of the wrapping layer contains a super water-absorbing material, and the wrapping layer forms a super water-absorbing powder cluster area inside the sponge; the content of the super-absorbent powder balls in the high-efficiency hemostatic sponge is 0.1-1 wt%, the water absorption rate is 60-120 times, and the porosity of the base material is more than 95%; comprises a skin-friendly sponge base material and super absorbent powder balls, and the surrounding area of the super absorbent powder balls is coated with a water-absorbing swelling material; the skin-friendly sponge base material is carboxymethyl chitosan or carboxymethyl starch or other materials, the super-absorbent powder groups are super-absorbent resin or other materials, and the water-absorbent swelling material is carboxymethyl chitosan or sodium alginate or other materials; the mass ratio of the core-spun structural microspheres to the sponge base material is about 1.82-15.67 wt%, and the molar ratio is about 1.11-10.12%.

Comprises a skin-friendly sponge base material and super absorbent powder balls, and the surrounding area of the super absorbent powder balls is coated with a water-absorbing swelling material.

The molecular weight of the carboxymethyl chitosan is 10000-80000, the deacetylation degree is more than or equal to 90%, and the carboxylation degree is more than or equal to 80%.

The mass ratio of the core-spun structural microspheres to the sponge base material is about 1.82-15.67 wt%, and the molar ratio is about 1.11-10.12%.

The preparation method comprises the following steps: firstly, granulating sodium alginate and high-water-absorption material powder through powder fog to form a high-water-absorption core-spun powder mass, dissolving carboxymethyl chitosan in deionized water, respectively adding the rest of additives and the high-water-absorption core-spun powder mass according to the proportion, continuously stirring for 30-60 min, and vacuumizing and defoaming after the raw materials are completely dissolved; and pouring the product into a plastic dish mold with the diameter of 75mm, standing at a low temperature for crosslinking for 6-24h to form gel, pre-freezing the gel at the temperature of-20 to-40 ℃ for 12-24 h, and then putting the gel into a freeze dryer for freeze drying for 24-48h to obtain the product.

The invention has the beneficial effects that: the efficient hemostatic dressing prepared by the invention has the advantages of high water absorption rate, high water absorption multiple and the like, can realize rapid hemostasis aiming at the condition of massive bleeding, is soft and elastic in surface and easy to attach, is beneficial to wound healing, is green and environment-friendly, and is suitable for being generally popularized and used.

Drawings

FIG. 1 is a schematic diagram of a high-efficiency hemostatic sponge structure according to the present invention;

FIG. 2 is a microscopic analysis diagram of the structure of the high-efficiency hemostatic sponge of the present invention;

FIG. 3 is a diagram of a water absorption curve testing apparatus according to the present invention;

FIG. 4 is a graph showing the comparative change in the water absorption (sample mass: 0.05 g) of the sponge of the present invention;

FIG. 5 is an electron micrograph of a pure CMCS of the present invention;

FIG. 6 is a cross-sectional electron microscope of CMS composite sponge of the present invention;

FIG. 7 is an electron microscope image of the core-spun dough of the present invention embedded in a sponge;

FIG. 8 is a diagram of the preparation of carboxymethyl chitosan-based composite hydrogel of the present invention.

Detailed Description

Example 1

a. A dressing comprising:

a dressing with hemostatic effect; such as a sponge dressing; gel dressings are also contemplated.

b. High-efficiency hemostatic dressing (sponge):

the hemostatic speed is faster than that of common dressing, and the hemostatic powder has high hemostatic capacity, still has certain strength after blood absorption, and has a series of characteristics of soft, elastic and easy adhesion on the surface.

c. High-efficient hemostasis composite dressing:

carboxymethyl chitosan (CMCS) or carboxymethyl starch (CMS) gel is taken as a base material, and then cross-linking is carried out by a cross-linking agent to improve the mechanical property, and a hemostatic agent is added as an auxiliary material for enhancing the hemostatic effect.

d. High (super) water absorption swelling powder dough:

the core-spun structure is formed by granulating by a method of powder and water mist, wherein the water mist is Sodium Alginate (SA) solution or other weak water-soluble materials. The core in the core-spun structure is made of high (super) water absorption materials, such as super water absorption resin (SAP), and the core and the SAP are compounded to form insoluble particles (at room temperature) with a surface swelling and coating shape.

e. The high-efficiency hemostatic dressing with the embedded particle structure comprises:

the water-soluble polymer material (CMCS/CMS) is used as a base material, and the particles in the embedded particle structure are the high (super) water absorption swelling powder groups. Uniformly dispersed in the base material dressing. Each of the above items can be considered to be extended, and there is a manufacturing method.

As shown in figure 1, carboxymethyl chitosan sponge is prepared by adopting a freeze drying method, particles prepared by using a high water absorption material through a water mist granulation method are dissolved in carboxymethyl sugar solution to serve as a factor for improving the water absorption rate, and uniform gel is formed by compounding carboxymethyl starch. Adding the high water absorption particles before gelation to uniformly disperse the particles into a gel system, pre-freezing the gel, and freeze-drying the gel by a freeze-drying method to prepare the carboxymethyl chitosan high-efficiency hemostatic sponge. The prepared carboxymethyl chitosan high-efficiency hemostatic sponge has good mechanical strength, and water absorption experiments also prove that the carboxymethyl chitosan high-efficiency hemostatic sponge has excellent water absorption rate and water absorption rate effect. Meanwhile, the raw materials are non-toxic and degradable, so that the environment-friendly material is green and can be recycled.

It is proved that in the carboxymethyl chitosan high-efficiency hemostatic sponge, particles formed by super absorbent resin play a role in greatly improving the hemostasis (water absorption) rate, and the carboxymethyl chitosan sponge is used as an adsorbent and a carrier of the particles. When the amount of the loaded high water absorption particles is increased or reduced, the water absorption effect is increased or reduced along with the increase or reduction of the amount of the loaded high water absorption particles, which indicates that the high water absorption particles are a key factor influencing the hemostasis (water absorption) rate of the sponge, but the high water absorption coated powder mass has the optimal loading amount due to the poor biocompatibility of a high water absorption material and the like.

The blank comparison sample has the advantages that the water absorption rate of the pure carboxymethyl chitosan sponge is lower and is 8-12 times, the water absorption rate of the sponge formed by compounding the pure carboxymethyl chitosan sponge with carboxymethyl starch is 28-35 times, and the water absorption rate of the compound sponge can reach 60-120 times when the concentration of the added high water absorption powder mass is 50-200 mg/L.

As shown in fig. 2, it can be seen that the powder balls in the composite sponge formed by the high water absorption swelling powder balls are uniformly attached to the interior of the carboxymethyl chitosan sponge, and when the dressing is contacted with water (blood), the action (expansion) of the super water absorption resin powder balls can be triggered, so that the adsorption amount and the absorption rate of the dressing to the super water absorption resin powder balls are greatly increased. However, the swelling ratio of the sponge is high, and the volume is greatly increased.

Since carboxymethyl starch sponge has poor water resistance and cannot be used for measuring the water absorption multiple of sponge by adopting the traditional immersion method, a self-made device is used for measuring the water absorption curve of the sponge so as to calculate the water absorption multiple of the sponge, and the self-made device is shown in figure 3. The water absorption was measured as follows: the material to be measured is cut into a sample of 2cm multiplied by 2cm, the mass W1 is precisely weighed, and 50mL of deionized water or physiological saline is poured into a plastic dish.

The water absorption rate and the water absorption capacity of the sponge added with the high water absorption powder mass are obviously improved through the graph 4. The water absorption rate reaches nearly 60 times, while the common CMCS sponge is only about 10 times.

As shown in fig. 5-7, different sponge SEM analyses: according to SEM scanning electron microscope test, the pure carboxymethyl chitosan sponge has larger aperture and complex and various internal structures; the sponge prepared by compounding carboxymethyl starch effectively improves the number of pores of the sponge body and reduces the pore diameter, and is one of the factors for increasing the water absorption capacity; the sponge after freeze-drying is added with the high water absorption powder balls, and the powder balls are embedded in the sponge according to the micro-morphology of the sponge.

Preparation of 2-3 wt% carboxymethyl chitosan solution: carboxymethyl chitosan (CMCS) is prepared into 2-3% solution. CMCS2g is added into 98 ml deionized water, and the solution can be stirred in 35 ℃ water bath to accelerate dissolution, or can be directly dissolved by mechanical stirring at normal temperature.

Preparing a super-absorbent core-spun powder dough: preparing sodium alginate solution from 2-5g of sodium alginate powder, spraying the super absorbent resin powder with a powder spray device at a certain spraying speed to make the water mist contact with the powder in the air, coating the powder with the water mist to form a powder mass, and collecting.

Preparing carboxymethyl chitosan-based composite hydrogel: (see FIG. 8).

Pre-freezing conditions: the temperature is from-20 ℃ to-40 ℃, the diameter of the plastic dish is 75mm, the thickness of the solution is 8-15mm, and the pre-freezing time is 6-24 h.

Freeze-drying conditions: placing the sample in a freeze dryer, and continuously freeze-drying for 24-48h at the freeze-drying temperature of-50 ℃ to-80 ℃ and under the pressure of less than 30 Pa.

Claims

1. A preparation method of a high-efficiency hemostatic dressing containing a high-water-absorption core-spun powder dough is characterized by comprising the following steps: firstly, sodium alginate and super absorbent resin are granulated through powder fog to form a high water absorption core-spun powder dough; then, dissolving carboxymethyl chitosan in deionized water, adding the rest of additives and the high-water-absorption core-spun powder dough according to the proportion, continuously stirring for 30-60 min, and vacuumizing and defoaming after the raw materials are completely dissolved; pouring the product into a plastic dish mold with the diameter of 75mm, and standing and crosslinking at low temperature for 6-24h to form gel; and finally, pre-freezing the gel at the temperature of between 20 ℃ below zero and 40 ℃ below zero for 12 to 24 hours, and then putting the gel into a freeze dryer to be freeze-dried for 24 to 48 hours at the temperature of between 50 ℃ below zero and 80 ℃ below zero and under the pressure of less than 30Pa, thus obtaining the high-efficiency hemostatic dressing.

2. The preparation method of the efficient hemostatic dressing containing the high water absorption cored flour dough according to claim 1, wherein the concentration of the carboxymethyl chitosan aqueous solution is 2-3 wt% after the carboxymethyl chitosan is dissolved in the deionized water.

3. The method for preparing the efficient hemostatic dressing containing the high water absorption core-spun powder dough according to claim 1, wherein the high water absorption core-spun powder dough is 0.1-1.0 wt% of the efficient hemostatic dressing.

4. The preparation method of the high-efficiency hemostatic dressing containing the high-water-absorption core-spun powder dough according to claim 1, wherein the molecular weight of the carboxymethyl chitosan is 10000-80000, the deacetylation degree is more than or equal to 90%, and the carboxylation degree is more than or equal to 80%.

5. The efficient hemostatic dressing containing the high-water-absorption core-spun powder dough prepared by the preparation method according to claim 1, wherein the porosity of the base material in the efficient hemostatic dressing is more than 95%, and the stream rate of the high-water-absorption core-spun powder dough is 60-120 times.