Efficient dispersion coagulant as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of blood coagulation accelerators, and particularly relates to an efficient dispersion coagulation accelerator as well as a preparation method and application thereof. The method comprises the following steps: at 65-80 DEG C, dissolving an inorganic salt procoagulant substance in an aqueous solution system containing a film-forming agent and a dispersing agent to react for 1-2 hours, then mixing with an ethanol solution in which polydimethylsiloxane is dissolved, adding a compound emulsifier, and then homogenizing and uniformly stirring at a high speed to obtain the efficient dispersion coagulant. The preparation method is simple in process and easy to operate, and raw materials are rich in source and easy to obtain. The high-efficiency dispersion coagulant is a suspension homogeneous liquid, has no obvious layering, has the pH value of 6-7 and the solid content of 7-8%, has the blood coagulation time as low as 8 minutes or less, is subjected to centrifugal treatment after blood coagulation, is complete in serum separation, and has no fibrin filament wall hanging and hemolysis phenomena. The blood collection container containing the efficient dispersion coagulant is used for 30 clinical biochemical tests, and the repeatability of the test result of the same clinical patient is good.

Description

Technical Field

[0001] The present invention belongs to the technical field of blood coagulants, and in particular relates to a highly efficient dispersed coagulant and a preparation method and application thereof. Background Art

[0002] Clinical medical testing is the primary means of clinical diagnosis. Of the samples used for clinical testing, 80% are venous blood samples, of which over 60% are serum samples separated from venous blood. A serum specimen refers to the clear liquid portion of blood that has been separated from the lower portion of the blood through high-speed centrifugation after blood coagulation and the separation of blood cells and fibrin. Therefore, obtaining serum requires sufficient blood coagulation. Blood coagulation is a complex and variable process that occurs after the blood is removed from the body and stimulated by external factors. It generally takes one hour for blood to coagulate and precipitate serum. Even using heated centrifugation, it takes about half an hour and is prone to hemolysis, which generally cannot meet the needs of laboratory testing. In the case of emergency blood matching or emergency diagnosis, the testing time will be prolonged, and even treatment may be delayed. Therefore, shortening the serum separation time and achieving rapid and accurate diagnosis are key to testing.

[0003] Coagulant-promoting vacuum blood collection tubes are widely used in medical testing. Blood coagulants are the core raw material for their production. Clinically, blood samples are added to these tubes to shorten clotting time during serum biochemical testing. Patent document CN102212514B discloses a blood coagulant for use in blood collection containers. The coagulant is composed of a blood wall inhibitor, thrombin, phosphatidylethanolamine, silica powder, and ethanol. This coagulant can cause blood to coagulate within 10 minutes, resulting in a long clotting time that cannot meet the rapid clotting requirements of blood testing. Furthermore, thrombin is sensitive to temperature and pH, requiring stringent storage conditions and a short shelf life. Patent document CN114813270B discloses a blood coagulant for blood collection tubes and its preparation method. The blood coagulant comprises nano-silica, vinyl pyrrolidone-vinyl acetate copolymer, polyethylene glycol stearate, and an ethanol aqueous solution. The resulting blood coagulant exhibits a short clotting time, radiation resistance, and an extended shelf life of up to one year without compromising product performance. It also exhibits no sedimentation or agglomeration during storage. However, the nano-silica requires grinding, which increases the process and costs. Furthermore, the nano-silica easily agglomerates within the formulation, necessitating strict control of the ratio. The mixture must ultimately be sieved to control dispersibility. Patent document CN105606412B discloses a production process for the blood coagulant. The formulation involves mixing pig brain powder and a supplementary formula (primarily composed of benzoic acid, kaolin, silica powder, and activated calcium phosphate) in a 1:1 weight ratio, stirring uniformly. The mixture is then sterilized by radiation and sealed in a light-proof plastic or glass container for storage at room temperature. The blood coagulant prepared by the above process is a powder, which has a simple production process and low cost. However, it needs to be prepared and operated before use, which increases the workload and is not widely used.

[0004] Furthermore, in clinical practice, nurses have been found to improve work efficiency by shaking vacuum blood collection tubes once or twice, or not at all, after drawing blood, and then centrifuging them to obtain serum. This operation can result in a concentration difference between the blood near the tube wall and the center, leading to uneven blood coagulation and residual fibrin. Therefore, it is necessary to develop a high-performance blood coagulant that is highly dispersed, has a short coagulation time, does not interfere with test results, and has excellent performance. Summary of the Invention

[0005] Based on this, the present invention aims to provide a method for preparing a highly efficient dispersible coagulant and the highly efficient dispersible coagulant prepared by the method. The preparation method is simple and safe; the coagulant can be efficiently dispersed and has a short coagulation time. Application to blood collection containers can address the problem of fibrin residue caused by uneven blood coagulation during blood collection. No mixing is required during use, no interference with test results occurs, and no clumping occurs during storage.

[0006] To achieve the above object, the present invention adopts the following technical solutions: The present invention provides a method for preparing a highly efficient dispersing coagulant, comprising the following steps: S1, heating and dispersing a styrene-maleic acid copolymer dispersant and a film-forming agent in purified water, then adding an inorganic salt procoagulant, and stirring to form a solution A; S2, dispersing polydimethylsiloxane in an ethanol solution to form a solution B; and adding the solution B to the solution A to form a solution C; S3, compounding Span and Tween emulsifiers to obtain a compound emulsifier; adding the compound emulsifier to the solution C, homogenizing, degassing and cooling to obtain a high-efficiency dispersing coagulant.

[0007] Furthermore, the heating and dispersion temperature in S1 is 65-80°C, and the heating time is 1-2h; the stirring and wetting time is 0.5-1h, and the stirring speed is 1000-2000r / min; the temperature of solution A in S1 is maintained at 65-80°C, and the process of adding solution B to solution A to form solution C in S2 is carried out at 65-80°C, and the compound emulsifier in S3 is added to the solution C and homogenized at 40-60°C.

[0008] Furthermore, the weight amounts of the raw materials added in S1 are: 5-10 parts of styrene-maleic acid copolymer dispersant, 5-10 parts of film-forming agent, 420-430 parts of purified water, and 20-40 parts of inorganic salt procoagulant.

[0009] Furthermore, the film-forming agent includes polyvinyl pyrrolidone, polyacrylic acid, acrylic acid copolymer, sodium carboxyethyl cellulose, polyvinyl alcohol or polyethylene glycol; preferably polyvinyl pyrrolidone, the molecular weight of the polyvinyl pyrrolidone is 1000~1300000, preferably 90000~1500000; the molecular weight range of the polyethylene glycol is 2000~6000; the inorganic salt procoagulant includes silicon dioxide, quartz powder, silica powder, diatomaceous earth or kaolin, preferably kaolin, and the kaolin is water-washed kaolin.

[0010] Furthermore, the weight ratios of the raw materials added in S2 are: 5-15 parts of polydimethylsiloxane and 420-430 parts of ethanol solution; the ethanol solution is an ethanol aqueous solution, and the mass ratio of ethanol to water in the ethanol aqueous solution is 1-2:2-3.

[0011] Furthermore, the weight portion of the compound emulsifier added in S3 is 10 to 30 parts; the homogenization process is performed at a homogenization speed of 5000 to 12000 r / min and a stirring time of 5 to 30 min.

[0012] Furthermore, the emulsifier includes a non-ionic polyol emulsifier, and the non-ionic polyol emulsifier includes a Span emulsifier and a Tween emulsifier; the mass ratio of the Span emulsifier to the Tween emulsifier in the compound emulsifier is 1:3~1:1; the Span emulsifier includes Span 20, Span 40, Span 60 or Span 80, and the Tween emulsifier includes Tween 20, Tween 40, Tween 60, or Tween 80; preferably, it is a compound of Span 80 and Tween 80.

[0013] The present invention further provides a high-efficiency dispersing coagulant prepared by the method for preparing the high-efficiency dispersing coagulant.

[0014] Furthermore, the high-efficiency dispersed coagulant has a coagulation time of ≤8 min, a pH of 6-7, and a solid content of 7-8%.

[0015] The present invention further provides a use of the above-mentioned high-efficiency dispersed coagulant in blood collection.

[0016] Finally, the present invention provides a blood collector containing the highly efficient dispersed coagulant.

[0017] The beneficial effects of the present invention are: 1. The method for preparing a highly efficient dispersed coagulant provided by the present invention is simple and easy to operate, and the raw materials are abundant and readily available. By using different addition sequences, the effective ingredients of the blood coagulant are increased, the coagulation time of the coagulant can be effectively controlled, and the shortcomings of the coagulant being difficult to disperse and prone to agglomeration and caking during use are improved. At the same time, through improvements to the system, the procoagulant substance is successfully encapsulated and modified, thereby improving its uniform dispersion throughout the solution, bringing into play the synergistic effect of the dispersant and emulsifier, and avoiding differences in product performance in subsequent processes, which affects product quality and production stability.

[0018] 2. The highly efficient dispersible coagulant provided by the present invention is a homogeneous suspension with no apparent stratification, a pH of 6-7, and a solids content of 7-8%. When applied to blood collection containers, the pH range is neutral, with no acidity or alkalinity impact on test results, more stable physical properties, and a good coagulant effect at a solids content of 7-8%. The coagulation time is as low as 8 minutes, and after coagulation, the blood is centrifuged to completely separate the serum, without fibrin adhesion or hemolysis.

[0019] 3. The blood collection container containing a highly efficient dispersible coagulant provided by the present invention is used for 30 clinical biochemical tests. The test was verified on 15 clinical patients. Blood was drawn from the same clinical patient three times, and the reproducibility of the test results was recorded. The results showed that the test results of the same clinical patient had good reproducibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the technical solution of the present invention, the following briefly introduces the drawings required for use in the embodiments or descriptions of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0021] Attachment Figure 1 The left picture shows the high-efficiency dispersed coagulant prepared in Example 1, and the right picture shows the coagulant prepared in Example 4.

[0022] Attachment Figure 2 This is a test chart of the coagulation effect of the high-efficiency dispersed coagulant prepared in Example 1; Attachment Figure 3 This is a test diagram of the coagulation effect of the coagulant prepared in Comparative Example 4. DETAILED DESCRIPTION

[0023] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. The embodiments mentioned are all implemented based on the technical solutions of the present invention, and detailed implementation processes are given. However, it should be noted that the scope of protection of the present invention is not limited to the following embodiments.

[0024] The present invention provides a method for preparing a highly efficient dispersing coagulant, comprising the following steps: S1, heating and dispersing a styrene-maleic acid copolymer dispersant and a film-forming agent in purified water, then adding an inorganic salt procoagulant, and stirring to form a solution A; Among them, styrene-maleic acid copolymer dispersants, whose carboxylic acid groups can be adsorbed on the particle surface through electrostatic interactions and hydrogen bonding, deflocculate the coagulant through steric stabilization, preventing particle agglomeration and effectively improving the dispersion stability of the particles in the dispersion medium, thereby achieving high dispersibility. The styrene-maleic acid copolymer dispersant used in this invention is DISPERBYK-190 dispersant from BYK Chemicals of Germany.

[0025] Film-forming agents include polyvinyl pyrrolidone, polyacrylic acid, acrylic acid copolymers, sodium carboxyethyl cellulose, polyvinyl alcohol, or polyethylene glycol. Film-forming agents contain hydroxyl, carboxyl, or ether groups. For example, polyvinyl pyrrolidone contains a large number of alcoholic hydroxyl and carbonyl groups, which can form hydrogen bonds with water molecules, increasing its solubility and improving its flow properties. This allows it to be used to prepare stable aqueous suspensions. Therefore, when using a blood collection container containing this coagulant, it rapidly disperses and dissolves into the blood, eliminating the need for a shaking step.

[0026] Inorganic salt-based procoagulants include silicon dioxide, quartz powder, silica powder, diatomaceous earth, or kaolin containing silicon. Taking kaolin as an example, the layered structure and surface micropores of this procoagulant give it good adsorption and ion exchange properties. By dissolving kaolin in an aqueous solution system containing a film-forming agent and a dispersant, the kaolin is successfully encapsulated and modified, improving the shortcomings of kaolin that are difficult to disperse and prone to agglomeration and caking during use, and overall improving the uniform dispersion of kaolin in the entire solution. In addition, kaolin has a negative surface charge at the pH value of blood. Upon contact with blood, it will quickly activate FⅫ or FⅪ, starting the intrinsic coagulation pathway, so that the coagulation process is evenly initiated throughout the blood collection tube, and fibrinogen is converted into fibrin filaments and the fibrin network is rapidly formed simultaneously, effectively controlling the coagulation time and avoiding the wall adhesion phenomenon, improving the effect of the coagulant, ensuring the quality of the serum, and no mixing is required during use.

[0027] S2, dispersing polydimethylsiloxane in an ethanol solution to form a solution B; and adding the solution B to the solution A to form a solution C; Among them, the polydimethylsiloxane in solution B is dispersed in the ethanol water medium in the form of extremely small droplets, preventing the collected blood from adhering to the inner wall of the blood collection container due to protein adsorption, causing errors in the test results. At the same time, it has defoaming properties, preventing the blood collection container from being affected by bubbles in the blood or separation gel on the clinical biochemical test results.

[0028] S3, compounding a Span-type emulsifier and a Tween-type emulsifier to obtain a compound emulsifier; adding the compound emulsifier to the solution C and homogenizing it to obtain a high-efficiency dispersing coagulant; The emulsifier is a nonionic polyol-based compound emulsifier. Span emulsifiers include Span 20, Span 40, Span 60, or Span 80, and Tween emulsifiers include Tween 20, Tween 40, Tween 60, or Tween 80. These emulsifiers are low-toxic, non-irritating, and offer greater emulsion stability than single emulsifiers. When formulated with Tween 80 as the primary emulsifier and Span 80 as the secondary emulsifier, a mass ratio of 1:3 to 1:1 achieves optimal homogeneous emulsification of the blood coagulant, resolving the issue of poor uniformity associated with wet coagulant addition. This improves the coagulant's sedimentation properties, preventing clumping after prolonged storage and extending its shelf life. Furthermore, the emulsifier possesses stabilizing, lubricating, dispersing, and solubilizing properties, creating a synergistic effect with the dispersant.

[0029] The following examples provide detailed examples of the technical solutions of the present invention. The experimental methods used in the following embodiments are conventional methods unless otherwise specified; the materials and reagents used are commercially available reagents and materials unless otherwise specified.

[0030] Example 1 The steps for preparing a highly efficient dispersing coagulant are as follows: (1) Measure 425 mL of purified water and place it in a container and dissolve 5 g of dispersant DISPERBYK-190 (BYK Chemical, Germany) and 10 g of polyvinyl pyrrolidone (BASF K90). Heat and stir at 65 °C for 1.5 h to dissolve. Then add 30 g of kaolin and set the stirring speed to 1500 r / min for 0.5 h to form a solution. The solution temperature is maintained at 65 °C. (2) Dissolve 10 g of polydimethylsiloxane in 500 mL of ethanol-water solution (the mass ratio of ethanol to water is 2:3) to form a polydimethylsiloxane ethanol solution, add the solution to the solution in step (1) and mix to form a mixed solution, and maintain the temperature of the mixed solution at 65°C; (3) Span 80 and Tween 80 were compounded in a weight ratio of 2:3 to form 20 g of compound emulsifier. After stirring evenly, the compound emulsifier was added to the mixed solution of step (3) and homogenized at 45°C. The stirring was set at a homogenization speed of 10,000 r / min for 15 minutes, and the mixture was allowed to stand for degassing. After cooling to room temperature, a high-efficiency dispersing coagulant was obtained.

[0031] Example 2 The steps for preparing a highly efficient dispersing coagulant are as follows: (1) Measure 420 mL of purified water and place it in a container and dissolve 7 g of dispersant DISPERBYK-190 (BYK Chemical, Germany) and 8 g of polyvinyl pyrrolidone (BASF K90). Heat and stir at 70 °C for 1 h to dissolve. Then add 20 g of kaolin and set the stirring speed to 1000 r / min for 0.5 h to form a solution. The solution temperature is maintained at 70 °C. (2) Dissolve 15 g of polydimethylsiloxane in 500 mL of ethanol-water solution (the mass ratio of ethanol to water is 1:3) to form a polydimethylsiloxane ethanol solution, add the solution to the solution in step (1) and mix to form a mixed solution, and maintain the temperature of the mixed solution at 70°C; (3) Span 80 and Tween 80 were compounded in a weight ratio of 1:3 to form 30 g of compound emulsifier. After stirring evenly, the compound emulsifier was added to the mixed solution of step (3) and homogenized at 50°C. The stirring was set at a homogenization speed of 8000 r / min for 25 minutes, and the mixture was degassed at rest. After cooling to room temperature, the highly efficient dispersing coagulant was obtained.

[0032] Example 3 The steps for preparing a highly efficient dispersing coagulant are as follows: (1) 424 mL of purified water was placed in a container and 9 g of dispersant DISPERBYK-190 (BYK, Germany) and 7 g of polyvinyl pyrrolidone (BASF K90) were dissolved. After heating and stirring at 70 °C for 2 h, 40 g of silica was added. The stirring speed was set to 2000 r / min and the mixture was stirred and wetted for 0.5 h to form a solution. The solution temperature was maintained at 70 °C. (2) Dissolve 5 g of polydimethylsiloxane in 500 mL of ethanol-water solution (the mass ratio of ethanol to water is 1:2) to form a polydimethylsiloxane ethanol solution, add the solution to the solution in step (1) and mix to form a mixed solution, and maintain the temperature of the mixed solution at 70°C; (3) Span 60 and Tween 40 were compounded in a weight ratio of 1:2 to form 15 g of compound emulsifier. After stirring evenly, the compound emulsifier was added to the mixed solution of step (3) and homogenized at 50°C. The stirring was set at a homogenization speed of 12000 r / min for 5 minutes, and the mixture was degassed at rest. After cooling to room temperature, the highly efficient dispersing coagulant was obtained.

[0033] Example 4 The steps for preparing a highly efficient dispersing coagulant are as follows: (1) 427 mL of purified water was placed in a container and 10 g of dispersant DISPERBYK-190 (BYK, Germany) and 5 g of polyethylene glycol PEG2000 (Aladdin) were dissolved. After heating and stirring at 80 °C for 1 h, 35 g of diatomaceous earth was added. The stirring speed was controlled at 1300 r / min and the mixture was stirred and moistened for 1 h to form a solution. The solution temperature was maintained at 80 °C. (2) Dissolve 13 g of polydimethylsiloxane in 500 mL of ethanol-water solution (the mass ratio of ethanol to water is 2:3) to form a polydimethylsiloxane ethanol solution, add the solution to the solution in step (1) and mix to form a mixed solution, and maintain the temperature of the mixed solution at 80°C; (3) Span 40 and Tween 80 were compounded in a weight ratio of 1:1 to form 10 g of compound emulsifier. After stirring evenly, the compound emulsifier was added to the mixed solution of step (3) and homogenized at 60°C. The mixture was stirred at a homogenization speed of 11000 r / min for 10 min, and the mixture was allowed to stand for degassing. After cooling to room temperature, the highly efficient dispersing coagulant was obtained.

[0034] Example 5 The steps for preparing a highly efficient dispersing coagulant are as follows: (1) 430 mL of purified water was placed in a container and 6 g of dispersant DISPERBYK-190 (BYK Chemical, Germany) and 6 g of polyethylene glycol PEG2000 (Aladdin) were dissolved. After heating and stirring at 75 °C for 1.5 h, 25 g of kaolin was added. The stirring speed was controlled at 1800 r / min and the mixture was stirred and moistened for 1 h to form a solution. The solution temperature was maintained at 75 °C. (2) 8 g of polydimethylsiloxane was dissolved in 500 mL of ethanol-water solution (the mass ratio of ethanol to water was 1:1) to form a polydimethylsiloxane ethanol solution, and the solution was added to the solution in step (1) and mixed to form a mixed solution. The temperature of the mixed solution was maintained at 75°C; (3) Span 80 and Tween 80 were compounded in a weight ratio of 2:3 to form 25 g of compound emulsifier. After stirring evenly, the compound emulsifier was added to the mixed solution of step (3) and homogenized at 55°C. The stirring was set at a homogenization speed of 5000 r / min for 30 minutes. After static degassing, the highly efficient dispersing coagulant was obtained.

[0035] Comparative Example 1 A coagulant was prepared. The preparation steps (2) and (3) of this comparative example were the same as those of Example 1, except that no dispersant was added in step (1).

[0036] Comparative Example 2 A coagulant was prepared. The preparation steps (1) and (2) of this comparative example were the same as those of Example 1, except that the emulsifier used in step (3) was Tween 80 single emulsifier.

[0037] Comparative Example 3 A coagulant was prepared. The preparation steps (1) and (2) of this comparative example were the same as those of Example 1, except that no emulsifier was added in step (3).

[0038] Comparative Example 4 A coagulant is prepared by measuring 430 mL of purified water into a container, adding 5 g of dispersant DISPERBYK-190 (BYK Chemicals, Germany), 5 g of polyvinyl pyrrolidone (BASF K90), 10 g of polydimethylsiloxane, 20 g of a composite emulsifier (Span 80:Tween 20) with a weight ratio of 2:3, and 30 g of kaolin, stirring for 2 h to dissolve, finally adding 500 mL of ethanol and stirring at a homogenization speed of 10,000 r / min for 15 min, and performing static degassing to obtain the coagulant.

[0039] Comparative Example 5 A coagulant was prepared. This comparative example was the same as Example 1, except that each reaction step was conducted at room temperature (25±5°C) without heating. In step (1), 3 g of dispersant DISPERBYK-190 (BYK Chemical, Germany) and 3 g of polyvinylpyrrolidone (BASF K90) were used. In step (3), only magnetic stirring was used for 15 minutes. Comparative Example 6 A coagulant was prepared. The preparation step (2) of this comparative example was the same as that of Example 1, except that in step (1), the dispersant and polyvinyl pyrrolidone were added to purified water and heated and stirred at 45° C. to dissolve, and the amount of kaolin added was 10 g; and in step (3), Span 80 and Tween 80 were compounded in a weight ratio of 3:1.

[0040] Comparative Example 7 A coagulant was prepared. The difference between this comparative example and Example 1 was that, in step (1), the dispersant and polyvinylpyrrolidine were added to purified water and heated and stirred at 85° C. for 2 h, and the amount of kaolin added was 15 g; the amount of polydimethylsiloxane added in step (2) was 20 g; and the emulsifier used in step (3) was Tween 80 single emulsifier.

[0041] The solution appearance, pH value, solid content, coagulation time, coagulation effect and biochemical effect of the highly efficient dispersible coagulant prepared in the above embodiment and the coagulant prepared in the comparative example were tested, and the test results were as follows: Figures 1-3 and shown in the table below.

[0042] 1. Appearance inspection: After the coagulant is fully stirred at 25±5°C, the properties of the solution are visually observed. The highly efficient dispersed coagulant solution prepared in the embodiment of the present invention is a suspended uniform liquid with no obvious stratification; while the coagulant in the comparative example has uneven precipitation and obvious stratification of the solution. Take, for example, Figure 1 The appearance pictures of the coagulants in Example 1 and Comparative Example 4 are given respectively. The pictures show that the highly efficient dispersed coagulant solution in Example 1 is a suspended uniform liquid with no obvious stratification ( Figure 1 Left). However, the coagulant solution in Comparative Example 4 had precipitation and obvious stratification ( Figure 1 right).

[0043] 2. pH and Solids Content Test: At 25±5°C, add a certain amount of the coagulant to be tested to the bottle to be tested. After thorough shaking, take an appropriate amount of sample into a beaker, adjust the temperature to 25°C, and measure the pH of the solution using a pH meter. Pipette 2-3 mL of the liquid onto a watch glass, dry it in an oven at 105°C±1°C for 2 hours, and calculate the mass percentage of the dried material to obtain the solids content. The data in the table above show that the pH of the highly dispersed coagulant solution in the examples is 6-7 and the solids content is 7-8%, meeting clinical technical requirements. The coagulant solutions in the comparative examples vary greatly, with pH values ​​ranging from 5-8 and solids contents between 5-9%.

[0044] 3. Test of coagulation time and coagulation effect: Apply the coagulant to the blood collector, do not mix the blood after drawing it, and record the time required for the blood to completely coagulate after contact with the coagulant, which is the coagulation time; and observe the amount of serum exudation after blood coagulation and whether the blood after coagulation can be completely separated from the serum and without fibrin hanging on the wall after centrifugation, and whether hemolysis occurs. The blood collectors containing the coagulants in Example 1 and Comparative Example 4 were tested, with 8 parallel samples in each group. The data in the above table show that the coagulation effect of the blood collector containing the highly efficient dispersed coagulant in Example 1 was normal, the coagulation time was within 8 minutes, and after the blood was centrifuged, all eight samples showed complete serum separation and no fibrin hanging on the wall ( Figure 2 ); The blood collection device containing the coagulant in Comparative Example 4 showed abnormal coagulation, and the coagulation time was much longer than that of the blood collection device containing the highly efficient dispersed coagulant in Example 1, with the highest coagulation time reaching nearly 20 minutes. After the blood was centrifuged, fibrin threads appeared on the wall of tubes 1, 2, and 3, and hemolysis occurred in tube 7 ( Figure 3 (shown in the circle on the middle tube).

[0045] 4. Biochemical Effect Evaluation Test: The coagulant in the comparative example had an abnormal coagulation effect, so it could not be tested for its biochemical effect. For the high-efficiency dispersed coagulant in the example, 30 clinical biochemical tests were performed, including: (liver function, kidney function, myocardial enzymes, amylase, etc.), electrolytes (serum potassium, sodium, chloride, calcium, phosphorus, etc.), serum immunology, thyroid function, etc. The test was verified in a total of 15 clinical patients. Blood was drawn from the same clinical patient three times, and the reproducibility of the test results was recorded. The results showed that the test results of the same clinical patient were well reproducible.

[0046] The above table shows that the highly efficient dispersible coagulant in the embodiment has stable physical properties and good coagulant effect. It is a blood coagulant with high dispersibility, high serum quality, short coagulation time, no interference with test results, and excellent performance. The specific analysis is as follows: By comparing the data of Example 1 and Comparative Examples 1 and 5, it can be seen that the present invention adopts a styrene-maleic acid copolymer dispersant, which can significantly improve the dispersibility of the coagulant. Its steric hindrance prevents the kaolin particles from agglomerating, and plays a synergistic dispersing effect with polyvinyl pyrrolidone, effectively improving the dispersion stability of the particles in the dispersion medium and obtaining high dispersibility.

[0047] It can be seen from the data of the comparative examples 2, 3, 6 and 7 that, by compounding Span 80 and Tween 80, the long-chain oleic acid of Span 80 can increase the viscosity of the solution and inhibit the formation of large droplets, the high HLB value of Tween 80 can significantly reduce the surface tension of the solution, the strong hydrophilicity can increase the water solubility rate, enhance the interfacial fluidity, and make the kaolin particles more evenly distributed, and the performance is better than that of a single emulsifier. This ratio achieves the best effect of homogeneous emulsification, and its wetting and dispersing properties synergize with the water-soluble dispersant to further improve the sedimentation performance of the blood coagulant and prevent the blood coagulant from agglomerating after being placed for a long time.

[0048] By comparing the data of Example 4, Comparative Examples 4, 5, 6 and 7, it can be seen that the addition order and preparation conditions have a great influence on the product performance of the coagulant. First, under appropriate temperature and reaction time conditions, kaolin is dissolved in an aqueous solution system containing a film-forming agent and a dispersant, and the kaolin is wrapped and modified to improve the uniform dispersion and hydrophilicity of the kaolin in the entire solution. Secondly, polydimethylsiloxane is added to prevent blood and fibrin fibers from adhering to the wall, which causes errors in the test results. Finally, a compound emulsifier is added to make the entire system a stable and uniform suspension system. The coagulant can be evenly adhered to the inner wall of the blood collection container after spraying and drying, and it is quickly redissolved after blood is drawn. The coagulant kaolin has a negative charge on its surface at the pH value of blood, which can directly contact and activate FⅫ or FⅪ, initiating the intrinsic coagulation pathway; at the same time, it quickly absorbs water molecules in the blood, concentrates platelets and thrombin in the blood, thereby accelerating the body's coagulation process, effectively avoiding the adhering to the wall phenomenon and effectively controlling the coagulation time, improving the effect of the coagulant, ensuring the quality of the serum, and no mixing is required during use.

[0049] The above description of the disclosed embodiments will enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein, but is to be construed in the widest manner consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a highly efficient dispersing coagulant, characterized in that: The steps include: S1, heating and dispersing a styrene-maleic acid copolymer dispersant and a film-forming agent in purified water, then adding an inorganic salt procoagulant, and stirring to form a solution A; S2, dispersing polydimethylsiloxane in an ethanol solution to form solution B; Adding the solution B to the solution A to form a solution C; S3, compounding Span and Tween emulsifiers to obtain a compound emulsifier; adding the compound emulsifier to the solution C, homogenizing, degassing and cooling to obtain a high-efficiency dispersing coagulant.

2. The method for preparing a highly efficient dispersing coagulant according to claim 1, wherein The heating and dispersion temperature in S1 is 65-80°C, and the heating time is 1-2 hours; the stirring and wetting time is 0.5-1 hour, and the stirring speed is 1000-2000 r / min; the temperature of solution A in S1 is maintained at 65-80°C, and the process of adding solution B to solution A to form solution C in S2 is carried out at 65-80°C, and the compound emulsifier in S3 is added to solution C and homogenized at 40-60°C.

3. The method for preparing a highly efficient dispersing coagulant according to claim 1, wherein: The weight ratios of the raw materials in S1 are as follows: 5-10 parts of styrene-maleic acid copolymer dispersant, 5-10 parts of film-forming agent, 420-430 parts of purified water, and 20-40 parts of inorganic salt procoagulant.

4. The method for preparing a highly efficient dispersing coagulant according to claim 1, wherein The film-forming agent includes polyvinyl pyrrolidone, polyacrylic acid, acrylic acid copolymer, sodium carboxyethyl cellulose, polyvinyl alcohol or polyethylene glycol, the molecular weight of the polyvinyl pyrrolidone is 1000-1300000, and the molecular weight range of the polyethylene glycol is 2000-6000; the inorganic salt procoagulant includes silicon dioxide, quartz powder, silica powder, diatomaceous earth or kaolin.

5. The method for preparing a highly efficient dispersing coagulant according to claim 1, wherein: The weight ratios of the raw materials added in S2 are: 5-15 parts of polydimethylsiloxane and 450-550 parts of ethanol solution; the ethanol solution is an ethanol aqueous solution, and the mass ratio of ethanol to water in the ethanol aqueous solution is 1-2:2-3.

6. The method for preparing a highly efficient dispersing coagulant according to claim 1, wherein: The weight portion of the compound emulsifier added in S3 is 10 to 30 parts; the homogenization process is performed at a homogenization speed of 5000 to 12000 r / min and a stirring time of 5 to 30 min.

7. The method for preparing a highly efficient dispersing coagulant according to claim 1, wherein: The mass ratio of the Span emulsifier to the Tween emulsifier in the compound emulsifier is 1:3 to 1:1; the Span emulsifier includes Span 20, Span 40, Span 60 or Span 80, and the Tween emulsifier includes Tween 20, Tween 40, Tween 60 or Tween 80.

8. A high-efficiency dispersing coagulant prepared by the method for preparing a high-efficiency dispersing coagulant according to any one of claims 1 to 7.

9. Use of the high-efficiency dispersed coagulant according to claim 8 in blood collection.

10. A blood collection device containing the highly efficient dispersed coagulant according to claim 8.

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