CN116059431A - Double-layer hemostatic dressing containing blood coagulation factors and preparation method thereof - Google Patents
Double-layer hemostatic dressing containing blood coagulation factors and preparation method thereof Download PDFInfo
- Publication number
- CN116059431A CN116059431A CN202111273623.2A CN202111273623A CN116059431A CN 116059431 A CN116059431 A CN 116059431A CN 202111273623 A CN202111273623 A CN 202111273623A CN 116059431 A CN116059431 A CN 116059431A
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- Prior art keywords
- layer
- dressing
- hemostatic
- double
- solution
- Prior art date
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Classifications
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- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
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- A—HUMAN NECESSITIES
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- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
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- A—HUMAN NECESSITIES
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- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
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- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
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Abstract
The invention relates to a double-layer hemostatic dressing containing a blood coagulation factor and a preparation method thereof, wherein a first layer of dressing of the double-layer hemostatic dressing comprises the following components in percentage by weight: fibrinogen 1-15 mg/cm 2 Prothrombin 0.01-5 mg/cm 2 Sugar 0.2-3.5 mg/cm 2 Sugar alcohol 0.2-3 mg/cm 2 Amino acid 0.05-1.5 mg/cm 2 Sodium chloride 0.01-0.45 mg/cm 2 Sodium citrate 0.05-1 mg/cm 2 Emulsifying agent 0.01-0.2 mg/cm 2 0 to 0.1mg/cm of solubilizer 2 Antioxidant 0.005-1 mg/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The second dressing layer contains absorbable high molecular polymer with the content of 1-5 mg/cm 2 . The double-layer hemostatic dressing provided by the invention can avoid the catalytic reaction of fibrinogen and prothrombin in the preparation process through optimizing the components, and can better ensure that the activity of fibrinogen in the dressing is not affected, thereby improving the hemostatic effect and stability of the product, and the preparation method is simple. The double-layer hemostatic dressing can be used for various hemostatic purposes, wound sealing purposes and the like in surgical operations and emergency occasions.
Description
Technical Field
The invention relates to the technical field of medical appliances, in particular to a double-layer hemostatic dressing containing a blood coagulation factor and a preparation method thereof.
Background
In the human coagulation mechanism, after the coagulation chain reaction is started, prothrombin in blood at a bleeding part is activated by calcium ions to become thrombin. Thrombin acts on fibrinogen, cleaves 4 peptide bonds at the ends of its 2 a alpha chains and 2B beta chains, releasing 2 fibrinopeptides a and two fibrinopeptides B, resulting in fibrin monomers. The fibrin monomer is spontaneously connected into an unstable fibrin polymer, and amide transfer occurs in the soluble fibrin polymer under the action of XIII coagulation factors and calcium ions to form stable covalent bonds, so that stable fibrin clots which are transversely, longitudinally and cross-connected are generated, and finally, the coagulation process is completed.
The blood coagulation factor hemostatic drugs used clinically at present mainly comprise: fibrinogen for injection, prothrombin for injection, thrombin powder for topical use, fibrinogen powder, a mixture of thrombin powder and fibrinogen powder, fibrin glue (fibrinogen solution and thrombin solution are mixed and sprayed into glue, also known as fibrin adhesive, fibrin sealant), fibrin patches (fibrinogen, sheet hemostatic material formed by freeze-drying or adhering thrombin and a carrier), and some other clotting factors for injection (e.g. factor VIII).
The fibrin patch is used as a sheet material, and has the advantages of convenient use, convenient carrying and storage, good adhesive effect and the like compared with other hemostatic medicines, but the prior fibrin patch contains fibrinogen and thrombin at the same time, so that the technical difficulty is that how to avoid the catalytic reaction of the fibrinogen and the thrombin in advance in the preparation. The existing method comprises the steps of grinding freeze-dried powder of fibrinogen and thrombin into powder with certain particle size, mixing with an organic solvent, coating the mixture on a carrier, and volatilizing the organic solvent; secondly, a low-temperature layering freezing method is adopted, and fibrinogen and thrombin do not react through low-temperature freezing. Both methods have great technical difficulties, the former has high requirements on powder particle size, organic solvent selection, coating process and environment temperature and humidity, and the latter has the problems of a rapid cooling mode, a freezing sequence and how to obtain a complete product.
The reason why the two ways are difficult to realize is that thrombin and fibrinogen can generate catalytic reaction in aqueous solution, so how to avoid the failure of products caused by the advanced reaction of fibrinogen in the preparation production process, and the improvement of the effective rate, the qualification rate and the aesthetic degree of the products is the problem to be solved when preparing the fibrin patches at present.
Disclosure of Invention
Based on the above, the invention aims to provide the double-layer hemostatic dressing containing the blood coagulation factors, which has the advantages of good stability, high qualification rate, better hemostatic effect, tight combination with wound surfaces, difficult falling off, short degradation time in vivo, simple preparation method and the like.
The specific technical scheme is as follows:
a dual layer hemostatic dressing comprising a clotting factor, a first layer dressing of the dual layer hemostatic dressing comprising the following components in amounts: fibrinogen 1-15 mg/cm 2 Prothrombin 0.01-5 mg/cm 2 Sugar 0.2-3.5 mg/cm 2 Sugar alcohol 0.2-3 mg/cm 2 Amino acid 0.05-1.5 mg/cm 2 Sodium chloride 0.01-0.45 mg/cm 2 Sodium citrate 0.05-1 mg/cm 2 Emulsifying agent 0.01-0.2 mg/cm 2 0 to 0.1mg/cm of solubilizer 2 Antioxidant 0.005-1 mg/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The second dressing layer contains absorbable high molecular polymer with the content of 1-5 mg/cm 2 。
Further, the fibrinogen content in the first dressing layer is 3-8 mg/cm 2 The prothrombin content is 0.1-2.5 mg/cm 2 。
Further, the sugar is selected from at least one of sucrose, lactose and trehalose.
Further, the sugar alcohol is mannitol.
Further, the amino acid is at least one selected from glycine, arginine and arginine derivatives thereof.
Further, the emulsifier is lecithin.
Further, the solubilizing agent is selected from at least one of tween 20 and tween 80.
Further, the antioxidant is at least one selected from vitamin C, vitamin E, vitamin B2, vitamin B6, rutin and albumin.
Further, the high molecular polymer is at least one selected from collagen, gelatin, chitosan, alginate, polylactic acid-glycolic acid copolymer and sodium carboxymethyl cellulose.
Further, the thickness of the double-layer hemostatic dressing is 0.05-7 mm.
The invention also provides a preparation method of the double-layer hemostatic dressing containing the blood coagulation factors.
The preparation method of the double-layer hemostatic dressing containing the blood coagulation factors comprises the following steps: weighing the components of the first layer of dressing according to the amount to prepare a first layer of dressing solution, and adding the first layer of dressing solution into a freezing vessel for freezing to obtain the first layer of dressing; and weighing the components of the second layer of dressing according to the amount to prepare a second layer of dressing solution, adding the second layer of dressing solution on the first layer of dressing, continuously freezing, and then carrying out vacuum freeze-drying to obtain the double-layer hemostatic dressing.
The preparation method of the double-layer hemostatic dressing containing the blood coagulation factors comprises the following steps: and weighing the components of the first layer of dressing according to the amount to prepare a first layer of dressing solution, freeze-drying the first layer of dressing solution, grinding the first layer of dressing solution into powder, and adsorbing the powder onto the second layer of dressing to obtain the double-layer hemostatic dressing. The second dressing can be obtained by a freezing method, and can also be directly purchased as a commercially available absorbable high polymer dressing.
Further, the adsorption mode is electrostatic adsorption.
The preparation method of the double-layer hemostatic dressing containing the blood coagulation factors comprises the following steps: weighing the components of the first layer of dressing according to the amount to prepare a first layer of dressing solution, dissolving the first layer of dressing solution with hexafluoroisopropanol after vacuum freeze drying, and then sucking the solution into a spinning machine to prepare a first layer of spinning; weighing the components of the second layer of dressing according to the amount, dissolving the components by using a mixed solution of chloroform and acetone, and then sucking the solution into a spinning machine to prepare a second layer of spinning; and superposing the second layer of spinning on the first layer of spinning to obtain the double-layer hemostatic dressing.
The preparation method of the double-layer hemostatic dressing containing the blood coagulation factors comprises the following steps: weighing the components of the first layer dressing according to the amount to prepare a first layer dressing solution, dissolving the first layer dressing solution with hexafluoroisopropanol after vacuum freeze-drying, then sucking the solution into a spinning machine to prepare a first layer spinning, and placing the first layer spinning on the second layer dressing to obtain the double-layer hemostatic dressing. The second dressing can be obtained by a freezing method, and can also be directly purchased as a commercially available absorbable high polymer dressing.
Further, the volume ratio of the chloroform to the acetone in the mixed solution of the chloroform and the acetone is 7:3.
Further, the spinning machine is an electrostatic spinning machine.
Further, the spinning condition was that an 18# needle was used, the voltage was 26kV, and the rate was 2.5ml/h.
Further, the freezing condition is-50+/-1 ℃ for 10-30 min.
The invention also provides a hemostatic kit which comprises the double-layer hemostatic dressing containing the blood coagulation factors and a calcium chloride solution, wherein the concentration of the calcium chloride solution is 15-25 g/L.
Further, the concentration of the calcium chloride solution is 20g/L.
Before use, the first layer dressing of the double-layer hemostatic dressing containing the blood coagulation factors can be soaked in the activating solution containing calcium chloride for 20-40 s, or the activating solution containing calcium chloride is sprayed on the surface of the first layer dressing, so that prothrombin can be rapidly activated into thrombin, the effect of catalyzing fibrinogen to be coagulated is achieved, and the hemostatic effect of the double-layer hemostatic dressing of the invention is further enhanced.
The invention provides a double-layer hemostatic dressing, which uses prothrombin to replace thrombin as a raw material, can avoid the catalytic reaction of fibrinogen in the preparation process, further ensures that the subsequent prothrombin can be effectively activated through the optimization of components and the preparation method, can not react with the fibrinogen in advance in the activation process, and can better ensure that the activity of the fibrinogen in the dressing is not influenced, thereby improving the hemostatic effect and stability of the product. Especially when the double-layer hemostatic dressing is prepared into a nano spinning structure, the activation of prothrombin is more facilitated on the premise of not influencing fibrinogen catalytic reaction.
The double-layer hemostatic dressing containing the blood coagulation factors can be activated by using a calcium chloride solution before use, so that the hemostatic effect of the double-layer hemostatic dressing is further enhanced. The inventor finds that when the calcium chloride solution with the concentration of 15-25 g/L is used for activation, the thrombin formed after the fibrinogen and the prothrombin are activated can be effectively prevented from catalyzing in advance, and particularly, when the concentration of the calcium chloride solution is 20g/L, the effect is better.
The double-layer hemostatic dressing has the advantages of good stability, high qualification rate, better hemostatic effect, tight combination with wound surfaces, difficult falling off and short in-vivo degradation time, is prepared by optimizing the formula, has a simple preparation method, and solves the technical difficulty of how to prevent fibrinogen and thrombin from catalyzing reaction in advance in the preparation in the prior art. The double-layer hemostatic dressing can be used for various hemostatic purposes, wound sealing purposes and the like in surgical operations and emergency occasions.
Detailed Description
The experimental methods of the present invention, in which specific conditions are not specified in the following examples, are generally conducted under conventional conditions or under conditions recommended by the manufacturer. The various chemicals commonly used in the examples are commercially available.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The terms "comprising" and "having" and any variations thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, apparatus, article, or device that comprises a list of steps is not limited to the elements or modules listed but may alternatively include additional steps not listed or inherent to such process, method, article, or device.
In the present invention, the term "plurality" means two or more. "and/or", describes an association relationship of an association object, and indicates that there may be three relationships, for example, a and/or B, and may indicate: a exists alone, A and B exist together, and B exists alone. The character "/" generally indicates that the context-dependent object is an "or" relationship.
Example 1
The embodiment provides a double-layer hemostatic dressing containing a blood coagulation factor, wherein a first layer of the double-layer hemostatic dressing comprises the following components in percentage by weight: fibrinogen 4.5mg/cm 2 Prothrombin 0.25mg/cm 2 Sucrose 3mg/cm 2 Mannitol 2.5mg/cm 2 Glycine 0.7mg/cm 2 L-arginine 0.15mg/cm 2 Sodium chloride 0.4mg/cm 2 Sodium citrate 0.4mg/cm 2 0.1mg/cm of soybean lecithin 2 Tween 20.05 mg/cm 2 Vitamin B 2 0.005mg/cm 2 Vitamin B 6 0.01mg/cm 2 And albumin 1.5mg/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The second dressing contains collagen with the content of 3mg/cm 2 。
The preparation method of the double-layer hemostatic dressing containing the blood coagulation factors comprises the following steps:
the first dressing solution was prepared at the component concentrations in table 1, with the solvent being water:
table 1 first layer dressing solution formulation
Preparing a second layer dressing solution: 6mg/ml collagen solution.
In a freeze-drying tray according to the volume of 0.05-0.25 ml/cm 2 (preferred in this embodiment, the concentration is 0.1ml/cm 2 ) Adding the first layer dressing solution, freezing at-50deg.C for 10-30 min (30 min is preferred in this example), and mixing at a concentration of 0.25-0.75 ml/cm 2 (preferred in this embodiment, the concentration is 0.5ml/cm 2 ) Adding the second layer solution, freezing at-50 ℃ and then carrying out vacuum freeze-drying to obtain the double-layer hemostatic dressing.
The double-layer hemostatic dressing obtained after vacuum freeze-drying in the embodiment has uniform appearance thickness and no phenomena of melting, collapse, non-drying or detachment, wherein the thickness of the first layer of dressing is about 1mm, and the thickness of the second layer of dressing is about 5mm.
Example 2
The embodiment provides a double-layer hemostatic dressing containing a blood coagulation factor, wherein a first layer of the double-layer hemostatic dressing comprises the following components in percentage by weight: fibrinogen 5.5mg/cm 2 Prothrombin 0.4mg/cm 2 Sucrose 2mg/cm 2 Lactose 1mg/cm 2 Mannitol 2mg/cm 2 Glycine 0.3mg/cm 2 Sodium chloride 0.1mg/cm 2 Sodium citrate 0.1mg/cm 2 0.1mg/cm of soybean lecithin 2 Tween 80.02 mg/cm 2 Vitamin B 2 0.005mg/cm 2 And vitamin E0.005 mg/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The second layer of dressing is chitosan fiber dressing.
The preparation method of the double-layer hemostatic dressing containing the blood coagulation factors comprises the following steps:
the first dressing solution was prepared at the component concentrations in table 2, with water as the solvent:
table 2 first layer dressing solution formulation
The first dressing solution was vacuum freeze-dried, ground to a powder (first dressing powder) and passed through a 100 mesh screen. It was adhered to a chitosan fiber dressing (Henan camel Beste medical instruments Co., ltd., type I, specification 5 cm. Times.10 cm) by electrostatic adsorption, per cm 2 Adsorbing 20-45 mg (30 mg is preferable in the embodiment) of the first layer dressing powder to obtain the double-layer hemostatic dressing.
The double-layer hemostatic dressing prepared by the embodiment has the advantages of smooth appearance, uniform powder, difficult falling off, good flexibility and crimping.
Example 3
The embodiment provides a double-layer hemostatic dressing containing a blood coagulation factor, wherein a first layer of the double-layer hemostatic dressing comprises the following components in percentage by weight: fibrinogen 3.5mg/cm 2 Prothrombin 0.3mg/cm 2 Sucrose 1mg/cm 2 Trehalose 0.8mg/cm 2 Mannitol 1.2mg/cm 2 Glycine 0.1mg/cm 2 Sodium chloride 0.15mg/cm 2 Sodium citrate 0.08mg/cm 2 0.1mg/cm of soybean lecithin 2 Vitamin B 2 0.003mg/cm 2 And rutin 0.002mg/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The second layer of dressing is collagen sponge dressing.
The preparation method of the double-layer hemostatic dressing containing the blood coagulation factors comprises the following steps:
the first dressing solution was prepared at the component concentrations in table 3, with water as the solvent:
table 3 formulation of first layer dressing solution
| Fibrinogen | 35mg/ml |
| Prothrombin | 3mg/ml |
| Sucrose | 10mg/ml |
| Trehalose | 8mg/ml |
| Mannitol (mannitol) | 12mg/ml |
| Sodium chloride | 1.5mg/ml |
| Sodium citrate | 0.8mg/ml |
| Soybean lecithin | 1mg/ml |
| Glycine (Gly) | 1mg/ml |
| Vitamin B 2 | 0.03mg/ml |
| Rutin | 0.02mg/ml |
The first dressing solution was lyophilized in vacuo and dissolved with hexafluoroisopropanol to 80mg/ml. The solution was sucked into the injection of the electrostatic spinning machine and spun into a first dressing layer with a 18# needle, voltage 26kV, and rate 2.5ml/h. And taking a collagen sponge dressing (the tin-free Bedi bioengineering Co., ltd., specification is 50mm multiplied by 50 mm) as a second dressing, and placing the first dressing on the second dressing to obtain the double-layer hemostatic dressing.
The first layer of the double-layer hemostatic dressing prepared by the embodiment is of a nanofiber structure, has the thickness of about 0.1mm, has larger specific surface area, and can be rapidly activated by being reacted with a calcium chloride solution.
Example 4
The embodiment provides a double-layer hemostatic dressing containing a blood coagulation factor, wherein a first layer of the double-layer hemostatic dressing comprises the following components in percentage by weight: fibrinogen 3.5mg/cm 2 Prothrombin 0.3mg/cm 2 Sucrose 1mg/cm 2 Trehalose 0.8mg/cm 2 Mannitol 1.2mg/cm 2 Glycine 0.1mg/cm 2 Sodium chloride 0.15mg/cm 2 Sodium citrate 0.08mg/cm 2 0.1mg/cm of soybean lecithin 2 Vitamin B 2 0.003mg/cm 2 And rutin 0.002mg/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The second dressing layer comprises polylactic acid-glycolic acid copolymer (PLGA 7525), and the content of the PLGA 7525 is 1.5mg/cm 2 。
The preparation method of the double-layer hemostatic dressing containing the blood coagulation factors comprises the following steps:
the first dressing solution was prepared at the component concentrations in table 4 with water as the solvent:
table 4 formulation of first layer dressing solution
| Fibrinogen | 35mg/ml |
| Prothrombin | 3mg/ml |
| Sucrose | 10mg/ml |
| Trehalose | 8mg/ml |
| Mannitol (mannitol) | 12mg/ml |
| Sodium chloride | 1.5mg/ml |
| Sodium citrate | 0.8mg/ml |
| Soybean lecithin | 1mg/ml |
| Glycine (Gly) | 1mg/ml |
| Vitamin B 2 | 0.03mg/ml |
| Rutin | 0.02mg/ml |
The first dressing solution was lyophilized in vacuo and dissolved with hexafluoroisopropanol to 80mg/ml. The solution was sucked into the injection of the electrostatic spinning machine and spun into a first dressing layer with a 18# needle, voltage 26kV, and rate 2.5ml/h. PLGA 7525 is dissolved into 120mg/ml by mixed solution of chloroform and acetone (volume ratio is 7:3), 18# needle is used for voltage 20kV and speed 1.8ml/h, and the spinning is overlapped on the first layer dressing to be used as the second layer dressing, thus obtaining the double-layer hemostatic dressing.
The two layers of the double-layer hemostatic dressing prepared by the embodiment are both of nanofiber structures, the thickness is about 0.1mm, the prothrombin is rapidly activated and is easy to fold, and the degradation time in vivo is shortened.
Example 5
In this example, the hemostatic effect of the double-layer hemostatic dressing prepared in examples 1 to 4 was studied using the bleeding of the liver wound of the rat as a model.
SD rats are selected as study subjects, the liver is injured by a direct trauma method, and then the double-layer hemostatic dressing prepared by the examples 1-4 with proper size is used for treatment. The experiments were divided into 5 groups, i.e. model group, examples 1-4, 4 animals per group, and the animals were treated for liver injury after intravenous injection of 3% sodium pentobarbital. The liver injury standard is 0.15cm deep, 1.5cm long and 1.2cm wide. The single administration, the liver administration dose was 2.5X2.2 (cm). Taking the double-layer hemostatic dressing prepared in the example 1 and the example 3, putting the first layer of dressing into 20g/L CaCl 2 Soaking in the solution for 30s, taking out, and directly attaching to liver injury surfaces of rats in the groups of the examples 1 and 3; taking the double-layer hemostatic dressing prepared in the examples 2 and 4, spraying 20g/L CaCl on the first layer of dressing 2 Solution 0.5ml/10cm 2 The liver injury surface of the rats of the groups of the example 2 and the example 4 is attached after 30 seconds; the wound surface of the rat in the model group is not subjected to hemostatic treatment. Covering gauze (weighed) to absorb all the blood flowing out, lightly pressing the gauze, observing 1 time of hemostasis every 4-5 seconds, and obtaining the bleeding time when the wound surface is not bleeding any more>20min is calculated according to 20 min), the weight of the yarn block and the hemostatic drug at the moment is weighed, and the bleeding amount is calculated. Bleeding amount (m 1) = [ post-hemostatic weight (g) -pre-hemostatic weight (g)]Specific gravity of blood (1.050 g/m 1).
The results are shown in Table 5 below:
table 5 effect of four dressings on bleeding amount and bleeding time of liver wound of SD rat
| Group of | n | Bleeding amount (ml) | Bleeding time(s) |
| Model group | 4 | 1.16±0.32 | 351±68 |
| Example 1 | 4 | 0.22±0.05** | 94±12** |
| Example 2 | 4 | 0.31±0.06** | 108±15* |
| Example 3 | 4 | 0.28±0.04** | 110±16* |
| Example 4 | 4 | 0.26±0.04** | 86±10** |
Note that: p <0.05, < p <0.01 compared to model group.
The results in Table 5 show that the 4 double-layer hemostatic dressings prepared in examples 1-4 have obvious hemostatic effects on rat liver wound surfaces, and the bleeding amount and bleeding time are obviously reduced compared with the model group. The double-layer hemostatic dressing prepared in example 4 has the advantages of optimal hemostatic effect and shortest bleeding time, because the double-layer hemostatic dressing prepared in example 4 has a nano spinning structure, the activation of prothrombin is more facilitated on the premise of not influencing the catalytic reaction of fibrinogen, and the activity of fibrinogen is ensured. The double-layer hemostatic dressing prepared in examples 1 to 4 can be obviously observed to be very tightly combined with the wound surface in the test process, and is not easy to fall off.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention.
Claims (10)
1. A dual layer hemostatic dressing comprising a clotting factor, wherein a first layer dressing of the dual layer hemostatic dressing comprises the following components in amounts: fibrinogen 1-15 mg/cm 2 Prothrombin 0.01-5 mg/cm 2 Sugar 0.2-3.5 mg/cm 2 Sugar alcohol 0.2-3 mg/cm 2 Amino acid 0.05-1.5 mg/cm 2 Sodium chloride 0.01-0.45 mg/cm 2 Sodium citrate 0.05-1 mg/cm 2 Emulsifying agent 0.01-0.2 mg/cm 2 0 to 0.1mg/cm of solubilizer 2 Antioxidant 0.005-1 mg/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The second dressing layer contains absorbable high molecular polymer with the content of 1-5 mg/cm 2 。
2. The blood coagulation factor-containing double-layer hemostatic dressing according to claim 1, wherein the fibrinogen content of the first layer dressing is 3-8 mg/cm 2 The prothrombin content is 0.1-2.5 mg/cm 2 。
3. The blood clotting factor-containing bilayer hemostatic dressing of claim 1, wherein the sugar is selected from at least one of sucrose, lactose, and trehalose;
and/or, the sugar alcohol is mannitol;
and/or the amino acid is selected from at least one of glycine, arginine and arginine derivatives thereof;
and/or, the emulsifier is lecithin;
and/or the solubilizer is selected from at least one of tween 20 and tween 80;
and/or the antioxidant is at least one selected from vitamin C, vitamin E, vitamin B2, vitamin B6, rutin and albumin.
4. The blood coagulation factor-containing bilayer hemostatic dressing according to claim 1, wherein the high molecular polymer is at least one selected from collagen, gelatin, chitosan, alginate, polylactic acid-glycolic acid copolymer and sodium carboxymethyl cellulose.
5. The method for preparing a double-layer hemostatic dressing containing a blood coagulation factor according to any one of claims 1 to 4, wherein the preparation method is as follows: weighing the components of the first layer of dressing according to the amount to prepare a first layer of dressing solution, and adding the first layer of dressing solution into a freezing vessel for freezing to obtain the first layer of dressing; and weighing the components of the second layer of dressing according to the amount to prepare a second layer of dressing solution, adding the second layer of dressing solution on the first layer of dressing, continuously freezing, and then carrying out vacuum freeze-drying to obtain the double-layer hemostatic dressing.
6. The method for preparing a double-layer hemostatic dressing containing a blood coagulation factor according to any one of claims 1 to 4, wherein the preparation method is as follows: and weighing the components of the first layer of dressing according to the amount to prepare a first layer of dressing solution, freeze-drying the first layer of dressing solution, grinding the first layer of dressing solution into powder, and adsorbing the powder onto the second layer of dressing to obtain the double-layer hemostatic dressing.
7. The method for preparing a double-layer hemostatic dressing containing a blood coagulation factor according to any one of claims 1 to 4, wherein the preparation method is as follows: weighing the components of the first layer of dressing according to the amount to prepare a first layer of dressing solution, dissolving the first layer of dressing solution with hexafluoroisopropanol after vacuum freeze drying, and then sucking the solution into a spinning machine to prepare a first layer of spinning; weighing the components of the second layer of dressing according to the amount, dissolving the components by using a mixed solution of chloroform and acetone, and then sucking the solution into a spinning machine to prepare a second layer of spinning; overlapping the second layer of spinning on the first layer of spinning to obtain the double-layer hemostatic dressing;
or the preparation method comprises the following steps: weighing the components of the first layer dressing according to the amount to prepare a first layer dressing solution, dissolving the first layer dressing solution with hexafluoroisopropanol after vacuum freeze-drying, then sucking the solution into a spinning machine to prepare a first layer spinning, and placing the first layer spinning on the second layer dressing to obtain the double-layer hemostatic dressing.
8. The method for preparing a double hemostatic dressing containing a blood coagulation factor according to any one of claims 5 to 7, wherein the freezing condition is-50±1 ℃ for 10 to 30min.
9. A hemostatic kit comprising a bilayer hemostatic dressing comprising a clotting factor of any one of claims 1-4 and a calcium chloride solution at a concentration of 15-25 g/L.
10. The hemostatic kit of claim 9, wherein the concentration of the calcium chloride solution is 20g/L.
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