CN111228562A - Starch hemostatic sponge and preparation method and application thereof - Google Patents
Starch hemostatic sponge and preparation method and application thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0036—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/146—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
Abstract
The invention provides a starch hemostatic sponge and a preparation method and application thereof, wherein the hemostatic sponge is composed of starch and glycerol, and the preparation method comprises the following steps: 1) heating and stirring starch, water and glycerol to gelatinize the starch; 2) injecting the gelatinized starch in the step 1) into a mold, and placing the mold in a freezing chamber for primary freezing; 3) adjusting the temperature of the freezing chamber in the step 2) to-10-5 ℃; 4) adjusting the temperature of the freezing chamber in the step 3) downwards, and performing secondary freezing to obtain a semi-finished product; 5) drying the frozen semi-finished product in the step 4) under a vacuum condition to obtain the starch hemostatic sponge. The hemostatic sponge has the advantages of simple components, good safety, high water absorption rate and good formability, can overcome the defects of complex components, safety risk, unsatisfactory water absorption rate and the like of similar materials prepared by the prior art, and has wide applications of body surface wound repair, internal hemostasis and the like.
Description
Technical Field
The invention relates to the technical field of hemostatic sponges and preparation methods thereof, in particular to a starch hemostatic sponge which can be degraded and absorbed in vivo and can be directly used for bloody wounds, a preparation method and application thereof.
Background
In emergency situations such as natural disasters, traffic accidents, battlefields and surgical operations, the life safety can be directly endangered by uncontrollable massive bleeding. According to statistics, during the years of 2011-2013, about 60 million people die from traffic accidents every year in China, wherein 85% of death reasons are massive hemorrhage at the initial stage of trauma. If the bleeding condition is controlled within 30 minutes after the accident occurs, the survival rate of the injured people can be improved by more than 40%. Blood is a natural microbial culture medium, and bleeding or oozing from the wound surface can also increase the probability of bacterial infection. Therefore, the rapid and effective hemostatic material is used for treating the bleeding wound surface in time, and is particularly important for reducing the number of accident deaths and the surgical operation risk.
The hemostatic materials on the market are various, the medical hemostatic sponge is one of the hemostatic materials widely used clinically, and the hemostatic sponge is commonly named as Sitexon Stypro gelatin hemostatic sponge, HemCon chitosan hemostatic yarn, strong oxidized cellulose hemostatic yarn, and polyvinyl alcohol hemostatic sponge of Merocel or Binge.
Collagen is the most abundant and widely distributed protein in animals, and gelatin is the partial hydrolysis product of collagen. In practical application, the gelatin sponge has the defects of poor hydrophilicity, small blood absorption amount, poor mechanical property and the like. Chitosan, also known as chitosan, is an alkaline polysaccharide substance mainly extracted from shrimps and crabs. The chitosan has good bacteriostatic and hemostatic functions, but the application of the chitosan in the biomedical field is limited by common toxic cross-linking agents such as glutaraldehyde and formaldehyde. In addition, when the animal-derived materials are applied to human bodies, the risks of virus transmission, immunogenicity and the like are increased, and strict requirements are placed on safety evaluation of animal-derived medical devices.
The Qiangsheng company initiates oxidized cellulose hemostatic products to be widely used for hemostasis of clinical operation wounds, and the oxidized cellulose hemostatic products have loose structures and good compliance. However, oxidized cellulose is acidic and may cause erythrocyte breakage when used in a bleeding site, resulting in hemolysis. The acidic environment also causes inflammation of surrounding tissues, slows the rate of tissue repair, and requires careful control of the amount of this material used in the body.
The polyvinyl alcohol sponge has good antibacterial performance and the capability of promoting wound healing, and is mainly used in ophthalmology, otorhinolaryngology and microsurgery. The composite material is obtained by condensation reaction of polyvinyl alcohol (PVA) and aldehyde compounds through a pore-forming agent foaming method, substances such as a pore-forming agent, a surfactant, formaldehyde, acid and the like need to be added in the preparation process, the formula is complex, the residual quantity of small molecular raw materials needs to be strictly monitored, and the safety risk is reduced.
Starch is the most common plant polysaccharide high molecular material, and can be extracted from corn, potato, cassava, sweet potato, kudzu root and other plants. Starch has been widely used in the fields of medical treatment, food, agriculture, industry, environment, etc. because of its good biocompatibility, degradability, reproducibility, and low price. The starch has safe sources, can avoid adverse reactions caused by animal-derived material foreign protein, has definite metabolic mechanism, can be hydrolyzed into glucose under the catalysis of enzyme, can be fully absorbed and metabolized by human bodies, has no toxic or side effect, and is an ideal raw material for preparing absorbable hemostatic materials.
Arista hemostatic powder produced by Medador company by taking starch as a raw material is taken as a hemostatic agent for emergency treatment and clinical operation, passes the American FDA certification as early as 2000, and formally enters the Chinese market in 2010. At present, the starch-based hemostatic material is still mainly applied clinically in the form of hemostatic powder. There are many documents or patent reports about starch sponge, the main raw materials include starch and various derivatives thereof, or starch and high polymer materials such as gelatin, chitosan, cellulose, sodium alginate and the like are compounded, the actual batch production is few in clinical application, and the starch hemostatic sponge is not seen in the market at home.
The starch sponge is mainly prepared by a vacuum freeze drying technology, and the following difficulties still exist: firstly, starch sponges have poor mechanical properties and poor moldability. The finished sponge product has the problems of low strength, poor toughness, easy breakage during pressing, incapability of keeping the integrity after absorbing water and the like. Secondly, in order to improve the water absorption and moldability of the sponge, components such as a crosslinking agent, a plasticizer, a thickener, and a binder are often added, and these additives are difficult to remove, some are toxic, and even if present in a trace amount in the sponge, may cause a safety hazard. Finally, in many documents or patents, starch is compounded with medical polymer materials such as chitosan, sodium alginate, cellulose, collagen, polyester, polyethylene glycol and the like to improve the defects of pure starch sponge performance, but some of the materials are of animal origin, and some metabolic mechanisms are unclear, so that the clinical application of the materials is greatly hindered, particularly the application in the aspect of internal hemostasis.
Chinese patent documents CN103275344, CN103265719, CN103319744 and CN103275345 disclose a technology for preparing starch hemostatic sponge by using modified starch, and the finished sponge product has higher water absorption rate and water absorption speed than similar products by processing modes such as ultrasound, heating, crosslinking and radiation. The modified starch is obtained by cutting, rearranging or introducing other chemical groups into starch molecules to change the structure of the starch molecules, so that the defects of the original starch in performance can be improved to a certain extent, but a plurality of chemical agents are often introduced in the treatment process, and the safety risk of the modified starch used as a biomedical material is increased.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide the starch hemostatic sponge which has simple components, good safety, high water absorption and good forming performance, can overcome the defects of complex components, safety risk, non-ideal water absorption and the like of similar materials prepared by the prior art, and has wide applications of body surface wound repair, internal hemostasis and the like. The invention also aims to provide a preparation method of the starch hemostatic sponge, which is simple, controllable and environment-friendly.
The purpose of the invention is realized by the following technical scheme:
a starch hemostatic sponge, the hemostatic sponge composed of starch and glycerol, the preparation method of the hemostatic sponge comprising the steps of:
1) heating and stirring starch, glycerol and water to gelatinize the starch;
2) injecting the gelatinized starch in the step 1) into a mold, and placing the mold in a freezing chamber for primary freezing, wherein the temperature of the primary freezing is minus 196 ℃ to minus 10 ℃;
3) adjusting the temperature of the freezing chamber in the step 2) to-10 ℃ to-5 ℃, and preserving the temperature for a period of time;
4) the temperature of the freezing chamber in the step 3) is reduced to minus 196 ℃ to minus 10 ℃, and secondary freezing is carried out to obtain a semi-finished product;
5) drying the semi-finished product in the step 4) under a vacuum condition to obtain the starch hemostatic sponge.
Preferably, the starch used in step 1) is one or a mixture of two or more, and the starch may be a native starch (native starch), such as: corn starch, waxy corn starch, sweet potato starch, cassava starch, potato starch, water caltrop starch, lotus seed starch, mung bean starch, wheat starch and gordon euryale seed starch; also modified starches which have been subjected to physical, chemical or biological modification, for example: soluble starch, pregelatinized starch, oxidized starch, etherified starch (such as carboxymethyl starch (also called carboxymethyl starch sodium)), esterified starch (such as acetate starch), cross-linked starch, grafted starch, dextrin, and composite modified starch.
Preferably, the mass ratio of starch to water in step 1) is 1:10 to 1:70, such as 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1: 70.
Preferably, the volume ratio of glycerol to water in step 1) is from 0.1:100 to 10:100, such as 0.1:100, 0.5:100, 1:100, 2:100, 5:100, 10: 100.
Preferably, the temperature of gelatinization in step 1) is 50-100 deg.C, such as 50 deg.C, 55 deg.C, 60 deg.C, 65 deg.C, 70 deg.C, 75 deg.C, 80 deg.C, 85 deg.C, 90 deg.C, 95 deg.C, 100 deg.C.
Preferably, the time for gelatinization in step 1) is 0.5 to 12h, for example 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12 h.
Preferably, the freezing chamber in step 2) is a device known in the art that can provide low temperature, such as a refrigerator, a freezer, a freeze dryer with pre-freezing function, and the like.
Preferably, the time for the first freezing in step 2) is 0.5 to 12 hours, for example, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, and 12 hours.
Preferably, the temperature of the primary freezing in step 2) is from-196 ℃ to-10 ℃, for example-10 ℃, 20 ℃, 30 ℃, 40 ℃, 50 ℃, 60 ℃, 70 ℃, 80 ℃ or 196 ℃.
Preferably, the temperature in step 3) is adjusted to-10 ℃ to-5 ℃ and then is kept for 0.5 to 12 hours, such as 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours and 12 hours.
Preferably, the temperature in step 3) is adjusted up to-10 ℃ to-5 ℃, e.g., to-10 ℃, 9 ℃, 8 ℃, 7 ℃, 6 ℃, 5 ℃, 4 ℃, 3 ℃, 2 ℃, 1 ℃, 0 ℃, 1 ℃, 2 ℃, 3 ℃, 4 ℃, 5 ℃.
Preferably, the time for the second freezing in step 4) is 0.5 to 12 hours, such as 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, and 12 hours.
Preferably, the temperature of the second freezing in step 4) is from-196 ℃ to-10 ℃, for example-10 ℃, 20 ℃, 30 ℃, 40 ℃, 50 ℃, 60 ℃, 70 ℃, 80 ℃ or 196 ℃.
Preferably, the drying is carried out in at least two stages in step 5), the temperature in the first stage being from-50 ℃ to 0 ℃, for example 0 ℃, 10 ℃ to-10 ℃, 20 ℃ to-30 ℃, 40 ℃ to-40 ℃ and 50 ℃ to-50 ℃; the temperature in the second stage is 0-80 deg.C, such as 0 deg.C, 10 deg.C, 20 deg.C, 30 deg.C, 40 deg.C, 50 deg.C, 60 deg.C, 70 deg.C, and 80 deg.C. The drying of the first stage may be carried out in a freeze dryer having a cold trap temperature of from 80 ℃ below zero to 60 ℃ below zero.
Preferably, the vacuum in step 5) is 0.1 to 30 Pa.
According to the invention, the water absorption rate of the starch hemostatic sponge is 14-40; the starch hemostatic sponge has smooth and fine surface without ice flowers and cracks when observed by naked eyes. The cross section is observed by a scanning transmission electron microscope, the inner part is an irregular porous structure, and the porosity can reach 90 percent at most. The density of the starch hemostatic sponge is 0.01-0.10g/cm3。
The invention also provides a preparation method of the starch hemostatic sponge, which comprises the following steps:
1) heating and stirring starch, glycerol and water to gelatinize the starch;
2) injecting the gelatinized starch in the step 1) into a mold, and placing the mold in a freezing chamber for primary freezing, wherein the temperature of the primary freezing is minus 196 ℃ to minus 10 ℃;
3) adjusting the temperature of the freezing chamber in the step 2) to-10 ℃ to-5 ℃, and preserving the temperature for a period of time;
4) the temperature of the freezing chamber in the step 3) is reduced to minus 196 ℃ to minus 10 ℃, and secondary freezing is carried out to obtain a semi-finished product;
5) drying the semi-finished product in the step 4) under a vacuum condition to obtain the starch hemostatic sponge.
The invention also provides the application of the starch hemostatic sponge, which is used for preparing a hemostatic material, or a material for promoting tissue healing, or a material for preventing the tissue or organ of a wound from being adhered to other surrounding tissues or organs.
The invention is used for preparing the hemostatic material with bloody wound surfaces of human, mammals, birds and reptiles.
The invention is used for preparing the hemostatic material on the surface of the human body, tissues and organs in the human body and tissues or organs in the body cavity with bloody wound surfaces, or used for surgical operation, wound first aid, laryngoscope, endoscope and endoscope.
According to the invention, the tissue comprises subcutaneous soft tissue, muscle tissue, bone tissue, brain tissue, nerve tissue, liver, kidney, spleen.
The invention has the beneficial effects that:
1. the invention improves the existing process for preparing the starch sponge by the vacuum freeze drying method, and can obtain the starch hemostatic sponge with perfect appearance and excellent performance under milder conditions. The freeze drying technology mainly comprises two parts of prefreezing and sublimation drying. The temperature and the cooling rate in the pre-freezing stage have important influence on the size and the shape of the hole in the sponge, and further influence the water absorption performance of the sponge. The general freezing process can cause the problems of uneven temperature, residual stress and the like in the solution, so that the sponge has cracks and cannot be molded. To solve this problem, researchers either add small molecule additives to help shape the sponge, or uniformly cool and rapidly freeze the solution at as low a temperature as possible (typically required to be below-40 ℃), which is not a small challenge to the performance of the lyophilization apparatus in mass production. The invention can balance the temperature of each part of the solution, eliminate the internal stress and effectively reduce the generation of cracks through a programmed three-stage freezing process, namely freezing-heating-freezing, can obtain the sponge with good appearance by pre-freezing at the temperature of minus 20 ℃, and reduces the performance requirement on equipment. In addition, the preparation process of the invention is simple and controllable, the prepared hemostatic sponge has smooth and fine surface, no cracks and ice flowers, and water absorption performance which is not inferior to that of similar products prepared by the prior art, and the prepared hemostatic sponge is soft and convenient to curl and is beneficial to being attached to the surface of skin or organs.
2. The method of the invention has no requirement on the types of starch, and is also suitable for native starch such as corn starch, sweet potato starch, cassava starch, potato starch, water caltrop starch, lotus seed starch, mung bean starch, wheat starch, gordon euryale seed starch and the like besides common modified starch and various starch derivatives thereof in the prior art. The finished product of the starch hemostatic sponge mainly comprises starch, has no other harmful components such as a cross-linking agent, a thickening agent, a plasticizer, a foaming agent, a humectant and the like, has a definite absorption and metabolism mechanism, is higher in safety and has a wider application range.
3. The preparation process is green and environment-friendly. In the preparation process, only starch raw materials, a small amount of glycerol and water are used, no additional additive is added, no pollutant is discharged, and the preparation method is eco-friendly and meets the green chemical concept vigorously advocated at the present stage of the country.
4. The starch hemostatic sponge has the characteristics of high water absorption rate, good hemostatic effect, good biocompatibility, simple and safe components, fast absorption and metabolism and the like, can be used for the bloody wound surface of the body surface and the internal tissue and organ of a human body, and can be used as a hemostatic material, a tissue healing promoting material and an anti-adhesion material in the scenes of surgical operation, wound first aid and the like. The preparation technology of the invention is simple and controllable, the water absorption performance, the formability and the mechanical property of the starch sponge can be effectively adjusted by changing the process parameters, and the process is pollution-free and environment-friendly, thereby being very beneficial to large-scale industrialization.
Drawings
Fig. 1 is a digital photograph and a scanning electron micrograph of a cross section of the hemostatic sponge 4.
FIG. 2 is a digital photograph and a scanning electron micrograph of a cross section of Japanese sponge 9.
Fig. 3 is a digital photograph of the hemostatic sponges of comparative examples 1-3.
Detailed Description
The preparation method of the present invention will be described in further detail with reference to specific examples. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
The experimental methods used in the following examples are all conventional methods unless otherwise specified; reagents, materials and the like used in the following examples are commercially available unless otherwise specified.
The starches used in the following examples are all commercially available.
Example 1
Putting 5g of corn starch, 150mL of water and 1mL of glycerol into a reaction vessel, heating and stirring to 100 ℃, and continuing stirring for 3 hours to gelatinize the starch; injecting the gelatinized starch into a mold, and pre-freezing for 4h in a freezing chamber of a freeze dryer at the temperature of minus 20 ℃; then the temperature of the freezing chamber is increased to 0 ℃ and kept for 4 h; then the temperature of the freezing chamber is reduced to 20 ℃ below zero for secondary pre-freezing, and the freezing chamber is kept for 4 hours; the cold trap of the freeze dryer begins to cool, the vacuum pump is turned on when the temperature is reduced to minus 60 ℃, the temperature of the freezing chamber is increased to minus 5 ℃ to begin the first stage drying when the vacuum degree is reduced to below 20Pa, and the drying is kept for 12 hours; then, the temperature is increased to 30 ℃ to start the second stage drying, and the drying is kept for 5 hours; obtaining the hemostatic sponge finished product 1.
Examples 2 to 36 and comparative examples 1 to 4
The other process steps are the same as example 1, and only differ in raw material ratio and process parameters. The selection, amount and key process parameters of each substance in the reaction are shown in table 1 below.
TABLE 1
The hemostatic sponge 1-36 obtained by the application has the advantages of smooth and fine surface, no cracks and ice flowers, softness and convenient curling. While the sponges prepared in comparative documents 1 to 4 had uneven surfaces, had cracks and ice flowers, and were not soft. For example, digital photographs and scanning electron micrographs of sections of the hemostatic sponges 4, 9, and digital photographs of the hemostatic sponges of comparative examples 1-3 are shown in fig. 1-3.
Test example 1
And (5) measuring the water absorption rate of the hemostatic sponge.
Precisely weighing hemostatic sponge with size of 2cm × 2cm × 0.5cm1) 20mL of purified water was added, and the mixture was left to stand for 2 hours and gently kneaded with fingers, taking care not to break the mixture. After sufficient water is absorbed, the sample is separated and precisely weighed (m)2) According to the water absorption capacity ═ m2-m1)/m1The water absorption rate of the hemostatic sponge was measured, and the results are shown in table 2 below.
TABLE 2
| Hemostatic sponge number | Water absorption rate | Hemostatic sponge number | Water absorption rate |
| 1 | 18.5 | 19 | 17.5 |
| 2 | 17.0 | 20 | 13.1 |
| 3 | 12.3 | 21 | 14.5 |
| 4 | 14.4 | 22 | 21.8 |
| 5 | 16.0 | 23 | 18.5 |
| 6 | 15.0 | 24 | 16.0 |
| 7 | 13.1 | 25 | 12.8 |
| 8 | 20.8 | 26 | 38.5 |
| 9 | 17.9 | 27 | 29.5 |
| 10 | 17.4 | 28 | 32.8 |
| 11 | 22.4 | 29 | 36.3 |
| 12 | 21.3 | 30 | 33.6 |
| 13 | 17.5 | 31 | 19.5 |
| 14 | 19.0 | 32 | 13.7 |
| 15 | 18.7 | 33 | 16.3 |
| 16 | 17.1 | 34 | 26.0 |
| 17 | 15.1 | 35 | 20.3 |
| 18 | 12.5 | 36 | 21.7 |
| Comparative example 1 | 8.3 | Comparative example 3 | 10.7 |
| Comparative example 2 | 9.1 | Comparative example 4 | 12.7 |
As can be seen from the examples and comparative examples in Table 2, the hemostatic sponge with higher water absorption rate can be obtained by using the specific 'freezing-heating-freezing' method of the present invention to prepare the hemostatic sponge.
Test example 2
Hemostatic effect of starch hemostatic sponge on rabbit liver hemorrhage model
The experimental method comprises the following steps: in rabbit liver laceration test, a surgical scalpel is used for cutting a cut with the length of 1 cm and the depth of 0.5cm on the liver to prepare a bleeding wound surface. The wound surface is stopped bleeding by being divided into an experimental group and a control group. In the experimental group, the hemostatic sponges 1 to 36 prepared in examples 1 to 36, respectively, were placed on the wound and lightly pressed, and the hemostatic effect was observed every half minute until no bleeding occurred. The sponge does not need to be removed after hemostasis. The control group was compressed with comparative examples 1-4 and gauze.
The experimental results are as follows: the hemostatic sponges 1-36 prepared in examples 1-36 above have a significant hemostatic effect. When the dried sponge contacts blood, the blood is quickly absorbed, the sponge-clot gelatinous body formed by swelling is tightly attached to the surface of the wound, and the sponge-clot gelatinous body can be used as a physical barrier to prevent the blood from seeping. All sponges in the experimental group can effectively control the bleeding of the liver wound surface within about 1 minute. The sponges of comparative examples 1-4 in the control group exhibited effective hemostasis in about 2 minutes, whereas complete hemostasis was difficult to achieve with gauze compression for more than 3 minutes.
Test example 3
Sponge Water absorption Rate test
The experimental method comprises the following steps: cutting sponge sample into 2 × 1 × 0.5cm3The middle of the rectangular bar is drawn to divide the rectangular bar into 1 multiplied by 0.5cm3Two parts. Precision scale (m)1) Then, one end is clamped by a pair of tweezers, half of the sponge sample is vertically immersed in water, and is lifted out of the water surface and suspended after 5s, 10s and 30s respectively, unabsorbed liquid is gently shaken off, and the sponge sample is precisely weighed (m)t)，mt-m1I.e. the water absorption capacity of the sponge in a certain period of time. Total Water absorption of sponge measured by test method (m) of test example 12-m1) And (4) calculating.
Test example 4
In vitro degradation experiments
The experimental method comprises the steps of adding about 0.1g of sample into 10mL of normal saline, carrying out water bath at 37 +/-1 ℃, dripping iodine tincture to show blue, adding 80U of α -amylase and 480U of saccharifying enzyme, observing color changes of 0h, 2h, 4h, 24h and 48h, and completely degrading the sample when the color changes to be colorless.
The experimental results are as follows: hemostatic sponges 1, 6, 11, 28 and 34 were completely degraded within 1 week. The degradation time of gelatin sponges is reported in the literature to be 4-6 weeks and the degradation time of oxidized cellulose is reported to be 3-6 weeks.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A starch hemostatic sponge, wherein the hemostatic sponge is composed of starch and glycerol, and the preparation method of the hemostatic sponge comprises the following steps:
1) heating and stirring starch, glycerol and water to gelatinize the starch;
2) injecting the gelatinized starch in the step 1) into a mold, and placing the mold in a freezing chamber for primary freezing, wherein the temperature of the primary freezing is minus 196 ℃ to minus 10 ℃;
3) adjusting the temperature of the freezing chamber in the step 2) to-10 ℃ to-5 ℃, and preserving the temperature for a period of time;
4) the temperature of the freezing chamber in the step 3) is reduced to minus 196 ℃ to minus 10 ℃, and secondary freezing is carried out to obtain a semi-finished product;
5) drying the semi-finished product in the step 4) under a vacuum condition to obtain the starch hemostatic sponge.
2. The starch hemostatic sponge of claim 1, wherein the starch used in step 1) is one or a mixture of two or more, and the starch may be natural starch, such as: corn starch, waxy corn starch, sweet potato starch, cassava starch, potato starch, water caltrop starch, lotus seed starch, mung bean starch, wheat starch and gordon euryale seed starch; also modified starches which have been subjected to physical, chemical or biological modification, for example: soluble starch, pregelatinized starch, oxidized starch, etherified starch (such as carboxymethyl starch), esterified starch (such as acetate starch), cross-linked starch, grafted starch, dextrin, and composite modified starch.
3. The starch hemostatic sponge according to claim 1 or 2, wherein the mass ratio of starch to water in step 1) is 1:10 to 1: 70.
Preferably, the volume ratio of glycerol to water in step 1) is from 0.1:100 to 10: 100.
Preferably, the temperature of the gelatinization reaction in step 1) is 50 to 100 ℃.
Preferably, the time of the gelatinization reaction in step 1) is 0.5 to 12 hours.
4. A starch haemostatic sponge according to any of claims 1-3, wherein the time for initial freezing in step 2) is 0.5-12 h.
Preferably, the temperature in the step 3) is adjusted to minus 10 ℃ to minus 5 ℃ and then is placed for 0.5 to 12 hours.
5. A starch haemostatic sponge according to any of claims 1-4, wherein the time for the second freezing in step 4) is 0.5-12 h.
6. A starch haemostatic sponge according to any of claims 1-5, wherein drying in step 5) is carried out in at least two stages, the first stage being at a temperature of-50-0 ℃ and the second stage being at a temperature of 0-80 ℃.
Preferably, the vacuum in step 5) is 0.1 to 30 Pa.
7. The starch hemostatic sponge of any one of claims 1-6, wherein the starch hemostatic sponge has a water absorption capacity of 14-40; the porosity of the starch hemostatic sponge reaches 90%; the density of the starch hemostatic sponge is 0.01-0.10g/cm3。
8. A method of making a starch hemostatic sponge of any one of claims 1-7, comprising the steps of:
1) heating and stirring starch, glycerol and water to gelatinize the starch;
2) injecting the gelatinized starch in the step 1) into a mold, and placing the mold in a freezing chamber for primary freezing, wherein the temperature of the primary freezing is minus 196 ℃ to minus 10 ℃;
3) adjusting the temperature of the freezing chamber in the step 2) to-10 ℃ to-5 ℃, and preserving the temperature for a period of time;
4) the temperature of the freezing chamber in the step 3) is reduced to minus 196 ℃ to minus 10 ℃, and secondary freezing is carried out to obtain a semi-finished product;
5) drying the semi-finished product in the step 4) under a vacuum condition to obtain the starch hemostatic sponge.
9. Use of a starch haemostatic sponge according to any of claims 1-7, for the manufacture of a haemostatic material, or for the manufacture of a material for promoting tissue healing, or for the manufacture of a material for preventing adhesion of a wounded tissue or organ to other surrounding tissues or organs.
10. The use according to claim 9, for the preparation of hemostatic materials for bloody wounds of humans, mammals, birds, reptiles.
Preferably, the hemostatic material is used for preparing a bloody wound surface of tissues or organs on the surface of a human body, in vivo tissues and organs and in a body cavity, or is used for surgical operation, wound emergency treatment, laryngoscope, endoscope and endoscopic hemostasis material.
Preferably, the tissue comprises subcutaneous soft tissue, muscle tissue, bone tissue, brain tissue, nerve tissue, liver, kidney, spleen.
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