Serum separation gel and preparation method thereof
By using petroleum resin, modified silica and dibutyl phthalate to prepare serum separation glue, the problem of poor fluidity and inversion properties of serum separation glue in the prior art under low temperature conditions is solved, and the process flow is simplified, cost reduction and product performance optimization are achieved.
Patent Information
- Application Number
- CN202411925818.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-25
- Publication Date
- 2025-03-28
AI Technical Summary
The existing serum serum separation glue has poor fluidity and reversibility under low temperature conditions, complex production process, a wide variety of raw materials, long cycles, and thixotropy still needs to be optimized.
Petroleum resin, modified silica and dibutyl phthalate are used as the main raw materials, and serum separation glue is prepared by heating and melting and high-speed dispersion and stirring. The modified silica is grafted by hydrolyzing polyacrylamide and sodium alginate to enhance its interaction ability.
The process flow is simplified, raw material costs are reduced, thixotropic performance is optimized, product stability and quality is improved, production cycle is shortened, and additional products are reduced.
Smart Images
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Abstract
Description
Technical Field
[0001] The present application relates to the technical field of medical materials, and in particular to a serum separation gel and a preparation method thereof. Background Art
[0002] Serum separation gel plays an important role in the medical field, especially in the collection and processing of blood samples. The analysis of blood samples usually requires the use of centrifugal force to separate whole blood into serum and plasma for subsequent testing.
[0003] Its working principle is: the general serum specific gravity is about 1.020g / cm 3 The specific gravity of blood clot is 1.080g / cm 3 , the separation gel density is maintained at 1.050 g / cm 3 Because of the existence of this specific gravity gradient density, in the vacuum blood collection tube for drawing blood, under the action of centrifugal force, the separation gel forms an isolation layer between serum and plasma, and keeps the serum and plasma in their original state without change, thereby obtaining high-quality serum (or plasma) samples for clinical testing.
[0004] Serum separation gel is essentially a viscous fluid, which contains a large number of hydrogen bonds in its structure. Due to the association of hydrogen bonds, a network structure is formed. Under the action of centrifugal force, the network structure is destroyed and becomes a fluid with low viscosity. When the centrifugal force disappears, the network structure is reformed and restored to a fluid with high viscosity. This property is called thixotropy, that is, when the temperature remains unchanged, a certain mechanical force is applied to this mucus colloid, and it can change from a high-viscosity gel state to a low-viscosity sol state. If the mechanical force disappears, it will return to the original high-viscosity gel state.
[0005] Separation gels are mainly divided into three categories: silicone rubber system, acrylic system and resin system. Silicone rubber system separation gels are rarely used due to their insufficient thixotropy and hydrolysis resistance. Acrylic system separation gels have become the most widely used type due to their good long-term stability, hydrophobicity and relatively low cost. However, they have poor fluidity and reversibility under low temperature conditions. In contrast, resin system separation gels exhibit excellent compatibility, radiation resistance, solvent resistance and stability, and are often used to manufacture high-end products and export. However, the production process of this type of separation gel is complex, with a wide variety of raw materials and a long cycle. It requires a large investment in manpower and material resources, and the quality control link is also relatively complex. Moreover, its thixotropy still needs to be optimized. Summary of the invention To solve the above problems, the present application hereby provides a serum separation gel and a preparation method thereof, aiming to prepare the serum separation gel with less raw materials and further optimize its thixotropic properties, so that the process flow is streamlined and efficient, greatly reducing the biochemical and physical reactions in the process from raw materials to finished products, reducing additional products, and thus shortening the production cycle.
[0007] In the first aspect, the serum separation gel provided in the present application adopts the following technical scheme: A serum separation gel, the raw materials used for preparation, in terms of weight percentage, include: 30% to 80% petroleum resin, 1% to 20% modified silicon dioxide, and 10% to 60% dibutyl phthalate.
[0008] Further, optionally, the raw materials used for preparation include, by weight percentage: 30% to 60% petroleum resin, 5% to 15% modified silicon dioxide, and 20% to 40% dibutyl phthalate.
[0009] Further, optionally, the raw materials used for preparation, by weight percentage, are: 60% petroleum resin, 10% silicon dioxide, and 30% dibutyl phthalate.
[0010] In some specific embodiments, the petroleum resin is C5 / C9 copolymerized hydrogenated petroleum resin, which has a softening point of 97-107° C. and a molecular weight of 500-1000.
[0011] By adopting the above technical scheme, the biochemical and physical reaction steps from raw materials to finished products can be greatly reduced, the generation of additional products can be reduced, and the process flow can be simplified, achieving multiple technical effects such as reducing raw material costs, optimizing thixotropic properties, streamlining the process flow, stabilizing product performance and improving quality. By utilizing a large number of hydrogen bonds on the structure of C5 / C9 copolymerized hydrogenated petroleum resin, hydrogen bond association can be directly achieved, and the thixotropic properties of the separation gel can be directly and effectively achieved.
[0012] In some specific embodiments, the modified silicon dioxide is obtained by hydrolyzing polyacrylamide and grafting sodium alginate onto the surface of nano silicon dioxide.
[0013] Further, optionally, the specific preparation method of the modified silicon dioxide is: Add nano-silicon dioxide into the reactor and slowly heat it up to 35-45°C; dissolve the silane coupling agent in a mixed solution A of water and ethanol, then add the preheated nano-silicon dioxide into the mixed solution A, heat it up to 55°C, adjust the pH value to 5.5-6.3, stir for 2-3h, take it out and wash it with distilled water for 2-3 times for standby use; Disperse sodium alginate and hydrolyzed polyacrylamide in a mixed solution B of water and ethylene glycol, heat to 36-39°C, adjust the pH value to weak acidity, stir for 0.2-0.4h, adjust the temperature to 45°C, keep warm for 1.5-2h, let stand, cool to room temperature, take out, wash with distilled water 3-5 times, and obtain.
[0014] By adopting the above technical solution, the introduction of modified silica significantly improves the thixotropic properties of the serum separation gel. Since the surface of the modified silica is grafted with functional groups such as hydrolyzed polyacrylamide and sodium alginate, these functional groups can form stronger interactions with matrix materials such as petroleum resin and dibutyl phthalate, thereby improving the viscosity stability and thixotropy of the serum separation gel. The optimization of the thixotropic properties enables the serum separation gel to maintain stable performance during storage and use, is not prone to stratification or precipitation, and improves the use effect of the product.
[0015] In a second aspect, the present application provides a method for preparing a serum separation gel using the following technical scheme: A method for preparing a serum separation gel comprises the following steps: respectively weighing petroleum resin, modified silicon dioxide and dibutyl phthalate, then putting the petroleum resin into a reaction kettle, heating and melting it, then adding the modified silicon dioxide and dibutyl phthalate, and dispersing and stirring at high speed to obtain the serum separation gel.
[0016] Further, optionally, the preparation steps are as follows: weigh petroleum resin, modified silica and dibutyl phthalate respectively, then put the petroleum resin into a reactor, heat and melt it at 150-200°C, then add modified silica and dibutyl phthalate, and disperse and stir at 2400-3500rpm for 3-4h to obtain the product.
[0017] By adopting the above technical scheme, multiple technical effects such as simplification, high efficiency, quality control and cost saving of the serum separation gel preparation process are achieved. These technical effects jointly improve the production efficiency and product quality of serum separation gel, and provide a better choice for applications in related fields. At the same time, the preparation method is also in line with the concept of green production and is conducive to achieving sustainable development.
[0018] In summary, this application includes the following beneficial effects: In the present application, a large number of hydrogen bonds on the structure of C5 / C9 copolymerized hydrogenated petroleum resin are directly used to achieve hydrogen bond association, and after being combined with modified silica after hydrolyzed polyacrylamide and sodium alginate surface grafting modification, the thixotropic properties of the separation gel can be further improved without losing stability, thereby streamlining the types of separation gel raw materials, reducing the interference of other components on blood samples, and improving detection accuracy; The present application achieves multiple technical effects such as simplification, high efficiency, quality control and cost savings in the preparation process of serum separation gel. These technical effects jointly improve the production efficiency and product quality of serum separation gel, and provide a better choice for applications in related fields. At the same time, the preparation method is also in line with the concept of green production and is conducive to achieving sustainable development. DETAILED DESCRIPTION
[0019] The present application is further described in detail below in conjunction with the examples. Except for the special instructions below, the raw materials used in the present application are all common commercially available materials.
[0020] Performance testing Tested in accordance with internal company standards / THSW 001-2025.
[0021] (I) Physical properties The appearance, specific gravity, thixotropic properties, phase separation, fluidity and radiation resistance of the serum separation gel prepared in each embodiment / comparative example were evaluated respectively.
[0022] Appearance inspection: Visually inspect the color and properties of the separation gel and check for impurities under light. The separation gel should meet the standard of "colorless to milky white, uniformly translucent to frosted glass-like gel, with no impurities visible to the naked eye"; Specific gravity and thixotropic properties: At room temperature of 25°C, take 4 13mm×10mm test tubes, put 1g of separation gel in each tube, add copper sulfate solutions with specific gravity of 1.045, 1.050, and 1.070 respectively, centrifuge for 5 minutes at a centrifugal force of 1900-2700g, the separation gel should be in the upper layer of copper sulfate with a specific gravity of 1.070, the mixed layer with a specific gravity of 1.050, and the lower layer of copper sulfate solution with a specific gravity of 1.045, and should meet the inspection standard of "the specific gravity of the separation gel should be 1.045-1.055 at 25°C, the separation gel should have gradient density thixotropic properties, and can effectively reverse when subjected to centrifugal force so that the blood formed components or blood clots with higher density are in the lower layer of the gel, and the serum or plasma with lower density are in the upper layer of the gel"; Phase separation: Gently shake the test tube of the separation gel obtained above, and observe the copper sulfate solution against the light to see whether it becomes turbid and whether there is colloid precipitated in the solution. It should meet the standard of "no colloid components should be precipitated after the separation gel is subjected to a certain shear force and the shear force disappears"; Fluidity: Take 4 13mm×75mm test tubes, add 1g of separation gel to each tube, place them vertically upward at room temperature for 12 hours, mark the surface of the separation gel, place 2 tubes upside down at room temperature, and place 2 tubes upside down in a 60℃ oven for 24 hours, and observe whether there is colloid flow or movement. It should meet the standard of "test tubes containing separation gel should not flow or move after being inverted at room temperature and 60℃ for 12 hours"; Tolerance: After 20 kg of separation gel product is irradiated with 15 kg of γ rays, the performance should not change.
[0023] (II) Clinical performance The serum separation gel prepared in each embodiment / comparative example was used to perform blood routine test and hemolysis test; Hemolysis test: Take 4 test tubes containing separation gel, add standard blood samples, centrifuge at a centrifugal force of 1900-2700g for 5 minutes, observe whether the upper serum turns red, and judge whether hemolysis occurs.
[0024] Examples 1-4 A serum separation gel, the raw materials for its preparation, in terms of mass percentage, include the following components: Table 1: Raw materials and dosages used for preparing serum separation gel in Examples 1-4 The above-mentioned modified silicon dioxide is prepared by the following preparation method: 213.89g of nano-silica was added to a reaction bottle, and the temperature was slowly raised to 35-45°C; 302.51g of γ-(2,3-epoxypropoxy)propyltrimethoxysilane was dissolved in 1.5L of a mixed solution A of water and ethanol, wherein the ratio of water to ethanol was 7:3 by mass; then the preheated nano-silica was added to the mixed solution A, the temperature was raised to 55°C, and the pH value was adjusted to 5.5-6.3, and after stirring for 2-3h, it was taken out and washed with distilled water for 2-3 times for standby use; Disperse 5.065g of sodium alginate and 8.314g of hydrolyzed polyacrylamide in 50ml of a mixed solution B of water and ethylene glycol, wherein the mass ratio of water to ethylene glycol is 4:6, heat to 36-39°C, adjust the pH value to weak acidity, stir for 0.2-0.4h, adjust the temperature to 45°C, keep warm for 1.5-2h, let stand, cool to room temperature, take out, wash with distilled water 3-5 times, and obtain the product.
[0025] The above-mentioned serum separation gel is prepared by the following preparation method: Weigh a predetermined amount of petroleum resin, modified silica and dibutyl phthalate respectively, then put the petroleum resin into a reaction kettle, heat and melt it at 150-200°C, then add modified silica and dibutyl phthalate, stir at 2400-3500rpm for 3-4h, then evacuate the system for 2-4h, and finally extrude at a uniform speed to obtain the product.
[0026] In the embodiment of the present application, the petroleum resin is a C5 / C9 copolymerized hydrogenated petroleum resin having a softening point of 97-107° C. and a molecular weight of 650.
[0027] Embodiment 5-8 A serum separation gel, the preparation method of which is the same as that of Example 1, the only difference being that the amounts of the raw materials used are different, as shown in the table below.
[0028] Table 2: Raw materials and amounts used in the preparation of serum separation gel in Examples 5-8 The performance of the serum separation gels prepared in Examples 1-8 of the present application was tested according to the above test standards, and the test results are shown in the table below.
[0029] Table 3: Serum separation gel performance test results in Examples 1-8 As can be seen from the above table, the various properties of the serum separation gels prepared by Examples 1-8 are excellent and meet the aforementioned test standards, and Example 6 has the best performance among all the examples, so it can be used as a preferred example; Analyzing the reasons, it may be: Modified silica has enhanced its compatibility with base materials such as petroleum resin by grafting hydrolyzed polyacrylamide and sodium alginate on its surface. This improved compatibility allows more efficient use of raw materials and reduces the proportion of unreacted or inefficiently used raw materials when preparing serum separation gel. At the same time, the grafting of hydrolyzed polyacrylamide and sodium alginate introduces more polar groups and segments, which can undergo conformational changes when subjected to shear force, thereby changing the viscosity of the serum separation gel. When the shear force stops, these groups and segments can quickly restore their original conformation, restoring the viscosity to its original state. This characteristic significantly improves the thixotropic properties of the serum separation gel. In addition, C5 / C9 copolymerized hydrogenated petroleum resin generally has excellent solubility, compatibility and stability. Its structure has a large number of hydrogen bonds, and the combination with modified silica can further improve the thixotropic properties of the separation gel.
[0030] Example 9 A serum separation gel, the preparation method of which is the same as that of Example 1, the only difference being that the type of petroleum resin used is different, which is C5 / C9 copolymerized petroleum resin in the present embodiment.
[0031] Example 10 A serum separation gel, the preparation method of which is the same as that of Example 1, the only difference being that the type of petroleum resin used is different, which is DCPD hydrogenated petroleum resin in the present example.
[0032] Embodiment 11 A serum separation gel, the preparation method of which is the same as that of Example 1, the only difference being that the specifications of the petroleum resin used are different. In the example of the present application, the molecular weight of the C5 / C9 copolymerized hydrogenated petroleum resin is 1200.
[0033] Example 12 A serum separation gel, the preparation method of which is the same as that of Example 1, the only difference being that the specifications of the petroleum resin used are different. In the example of the present application, the molecular weight of the C5 / C9 copolymerized hydrogenated petroleum resin is 450.
[0034] Comparative Example 1 A serum separation gel, the preparation method of which is the same as that of Example 1, the only difference being that an equal amount of silicon dioxide is used instead of modified silicon dioxide, that is, the silicon dioxide used in the example of the present application is not modified.
[0035] Comparative Example 2 A serum separation gel, purchased from SEKISUI, Japan, with a specification of 25kg / barrel.
[0036] The performance of the serum separation gels prepared in Examples 9-12 of the present application and Comparative Examples 1-2 was tested according to the above test standards, and the test results are shown in the table below.
[0037] Table 4: Serum separation gel performance test results in Examples 9-12 and Comparative Examples 1-2 As can be seen from the above table, there is no significant difference in performance between the separation gel in Comparative Example 2 and Example 1 of the present application. It can be seen that the serum separation gel prepared from the simplified separation gel preparation raw materials of the present application can achieve the same performance as the serum separation gel on the market, and the preparation process is simple, which greatly shortens the production cycle; In addition, the various properties of the separation gels prepared in Examples 9-12 and Comparative Example 1 decreased to varying degrees compared with those in Example 1; in Examples 9 and 10, precipitation occurred in the phase separation test; in Examples 11 and 12, the colloids flowed and moved; while in Comparative Example 1, its specific gravity did not meet the standard and its thixotropic properties were poor, and the colloids also flowed and moved and contained less blood, which means that in practical applications, serum separation cannot be performed well and the accuracy is insufficient.
[0038] The above results show that the petroleum resin should preferably be C5 / C9 hydrogenated copolymer petroleum resin, the molecular weight of which should be 500-1000, and the silica should be modified silica obtained by grafting nano-silica on the surface of hydrolyzed polyacrylamide and sodium alginate.
[0039] The above are all modifications without creative contribution or solutions that obviously constitute technical inspiration that can be made to the present embodiment as needed by technical personnel in this field after reading this specification, but they should be protected by patent law as long as they are within the scope of the claims of this application.
Claims
1. A serum separation gel, characterized in that The raw materials used for preparation, by weight percentage, include: Petroleum resin 30%~80%, modified silica 1%~20%, dibutyl phthalate 10%~60%.
2. The serum separation gel according to claim 1, characterized in that The raw materials used for the preparation include, by weight percentage, 30% to 60% of petroleum resin, 5% to 15% of modified silicon dioxide, and 20% to 40% of dibutyl phthalate.
3. The serum separation gel according to claim 1, characterized in that The raw materials used in the preparation are, by weight percentage, 60% petroleum resin, 10% silicon dioxide, and 30% dibutyl phthalate.
4. The serum separation gel according to claim 1, characterized in that The petroleum resin is C5 / C9 copolymerized hydrogenated petroleum resin, with a softening point of 97-107° C. and a molecular weight of 500-1000.
5. The serum separation gel according to claim 1, characterized in that The modified silicon dioxide is obtained by hydrolyzing polyacrylamide and grafting the surface of sodium alginate onto nano silicon dioxide.
6. The serum separation gel according to claim 5, characterized in that The specific preparation method of the modified silicon dioxide is: Add nano-silicon dioxide into the reactor and slowly heat it up to 35-45°C; dissolve the silane coupling agent in a mixed solution A of water and ethanol, then add the preheated nano-silicon dioxide into the mixed solution A, heat it up to 55°C, adjust the pH value to 5.5-6.3, stir for 2-3h, take it out and wash it with distilled water for 2-3 times for standby use; Disperse sodium alginate and hydrolyzed polyacrylamide in a mixed solution B of water and ethylene glycol, heat to 36-39°C, adjust the pH value to weak acidity, stir for 0.2-0.4h, adjust the temperature to 45°C, keep warm for 1.5-2h, let stand, cool to room temperature, take out, wash with distilled water 3-5 times, and obtain.
7. The method for preparing the serum separation gel according to any one of claims 1 to 6, characterized in that: The preparation steps include: Weigh petroleum resin, modified silicon dioxide and dibutyl phthalate respectively, then put the petroleum resin into a reaction kettle, heat and melt, then add the modified silicon dioxide and dibutyl phthalate, and disperse and stir at high speed to obtain the product.
8. The method for preparing the serum separation gel according to claim 7, characterized in that, The specific preparation steps are as follows: Weigh petroleum resin, modified silicon dioxide and dibutyl phthalate respectively, then put the petroleum resin into a reaction kettle, heat and melt at 150-200°C, then add modified silicon dioxide and dibutyl phthalate, and disperse and stir at 2400-3500rpm for 3-4h to obtain the product.