1. The resin for the serum separation gel is characterized by being prepared from the following raw materials: hydroxyethyl acrylate, butyl acrylate, 2-mercaptoethanol, butyl acetate, a thixotropic agent, an initiator and modified nano titanium dioxide, wherein the thixotropic agent is a copolymer of 2-methyl-2-acrylic acid, 2-acrylonitrile and 2-butyl acrylate, and the modified nano titanium dioxide is organic surface modified nano titanium dioxide.

2. The resin for a serum separation gel according to claim 1, wherein the raw materials are in parts by weight as follows: 85-115 parts of hydroxyethyl acrylate, 4-8 parts of butyl acrylate, 6-11 parts of 2-mercaptoethanol, 90-130 parts of butyl acetate, 2-5 parts of thixotropic agent, 2-5 parts of initiator and 2-4 parts of modified nano titanium dioxide.

3. The method for preparing a resin for a serum separation gel according to claim 1 or 2, comprising the steps of:

1) mixing part of hydroxyethyl acrylate, butyl acrylate, 2-mercaptoethanol, butyl acetate and a thixotropic agent to obtain a premix A, mixing the rest of hydroxyethyl acrylate, butyl acrylate, 2-mercaptoethanol, the thixotropic agent and part of an initiator to obtain a premix B, mixing the rest of the initiator and part of butyl acetate to obtain a premix C, and mixing the modified nano titanium dioxide and the rest of butyl acetate to obtain a premix D;

2) heating the premix A, dropwise adding the premix B into the premix A, and carrying out heat preservation reaction;

3) adding and dripping premix C into the reaction liquid in the step 2), and then carrying out heat preservation reaction;

4) adding premix D into the reaction liquid obtained in the step 3), and then heating and distilling to obtain the resin for the serum separation gel.

4. The preparation method of claim 3, wherein in step 1), the premix A comprises 9-12 parts by weight of hydroxyethyl acrylate, 2-4 parts by weight of butyl acrylate, 2-4 parts by weight of 2-mercaptoethanol, 80-100 parts by weight of butyl acetate and 2-4 parts by weight of thixotropic agent, the premix B comprises 80-100 parts by weight of hydroxyethyl acrylate, 2-4 parts by weight of butyl acrylate, 4-7 parts by weight of 2-mercaptoethanol, 2-4 parts by weight of initiator and 0.1-1 part by weight of thixotropic agent, the premix C comprises 0.5-1 part by weight of initiator and 5-15 parts by weight of butyl acetate, and the premix D comprises 2-4 parts by weight of modified nano titanium dioxide and 5-15 parts by weight of butyl acetate.

5. The method as claimed in claim 3, wherein the heating temperature in step 2) is 112-117 ℃; preferably, in the step 2), the premix B is added dropwise within 1-4h, the temperature of the heat preservation reaction is 120-125 ℃, and the time of the heat preservation reaction is 0.5-2 h.

6. The preparation method as claimed in claim 3, wherein in the step 3), the premix C is dripped within 10-30min, the temperature of the heat preservation reaction is 120-125 ℃, and the time of the heat preservation reaction is 2-4 h.

7. The method according to claim 3, wherein in the step 4), the distillation is performed at 195 ± 3 ℃ for 4-5 hours under reduced pressure.

8. A serum separation gel, which is characterized by comprising 900-1100 parts by weight of the serum separation gel resin of claim 1 or 2, 15-25 parts by weight of fumed silica and 40-50 parts by weight of a thixotropic agent.

9. The serum separation gel of claim 7, wherein the thixotropic agent is triethanolamine.

10. The method for preparing a serum separation gel according to claim 7 or 8, comprising the steps of:

1) the resin for the serum separation gel is firstly stirred and mixed with the fumed silica under vacuum, and then the thixotropic agent is added for continuous vacuum stirring;

2) vacuumizing the materials uniformly stirred in the step 1) in a closed container, standing and defoaming to obtain the serum separation gel.

Background

The serum separation gel is a viscous fluid, and the structure of the serum separation gel contains a large number of hydrogen bonds, and a network structure is formed due to the association of the hydrogen bonds. Under the action of centrifugal force, the net structure is broken down and becomes a fluid with low viscosity. The net structure is reformed when the centrifugal force disappears. By utilizing the characteristic, the serum separation gel can be prepared. When the separating gel and the coagulated blood are centrifuged in the same test tube, the separating gel forms a colloidal isolating layer between the serum and the blood clot to separate the serum from the blood clot. Thereby improving the yield of the serum, preserving the serum in the original state, simplifying the clinical examination process and improving the working efficiency.

However, the existing domestic serum separation gel has certain product defects, such as phase separation, low-temperature fluidity, low-temperature reversibility, aging resistance reversibility and the like, and therefore, the development of a serum separation gel is urgently needed, so that the product performance of the serum separation gel is equivalent to or superior to that of an imported product, the market is obtained, and the domestic and foreign markets are expanded.

Disclosure of Invention

The present invention is directed to solving at least one of the problems of the prior art described above. Therefore, the invention provides a novel resin for serum separation gel, serum separation gel and preparation methods thereof.

According to an aspect of the present invention, there is provided a resin for a serum separation gel, the resin for a serum separation gel being made from raw materials including: hydroxyethyl acrylate, butyl acrylate, 2-mercaptoethanol, butyl acetate, a thixotropic agent, an initiator and modified nano titanium dioxide, wherein the thixotropic agent is a copolymer of 2-methyl-2-acrylic acid, 2-acrylonitrile and 2-butyl acrylate, and the modified nano titanium dioxide is organic surface modified nano titanium dioxide. The thixotropic agent acts primarily to increase the viscosity of the resin. The modified nano titanium dioxide is used as a hydrophobic agent, so that the polymer structure of the resin has better hydrophobicity, and performance indexes such as oil drops of the product can be improved.

In some embodiments of the invention, the initiator is benzoyl peroxide tert-butyl.

In some embodiments of the invention, the starting materials are in the following parts by weight: 85-115 parts of hydroxyethyl acrylate, 4-8 parts of butyl acrylate, 6-11 parts of 2-mercaptoethanol, 90-130 parts of butyl acetate, 2-5 parts of thixotropic agent, 2-5 parts of initiator and 2-4 parts of modified nano titanium dioxide.

The invention also provides a preparation method of the resin for the serum separation gel, which comprises the following steps:

1) mixing part of hydroxyethyl acrylate, butyl acrylate, 2-mercaptoethanol, butyl acetate and a thixotropic agent to obtain a premix A, mixing the rest of hydroxyethyl acrylate, butyl acrylate, 2-mercaptoethanol, the thixotropic agent and part of an initiator to obtain a premix B, mixing the rest of the initiator and part of butyl acetate to obtain a premix C, and mixing the modified nano titanium dioxide and the rest of butyl acetate to obtain a premix D;

2) heating the premix A, dropwise adding the premix B into the premix A, and carrying out heat preservation reaction;

3) adding and dripping premix C into the reaction liquid in the step 2), and then carrying out heat preservation reaction;

4) adding premix D into the reaction liquid obtained in the step 3), and then heating and distilling to obtain the resin for the serum separation gel.

In some embodiments of the invention, in step 1), the premix a consists of 9 to 12 parts by weight of hydroxyethyl acrylate, 2 to 4 parts by weight of butyl acrylate, 2 to 4 parts by weight of 2-mercaptoethanol, 80 to 100 parts by weight of butyl acetate and 2 to 4 parts by weight of thixotropic agent, the premix B consists of 80 to 100 parts by weight of hydroxyethyl acrylate, 2 to 4 parts by weight of butyl acrylate, 4 to 7 parts by weight of 2-mercaptoethanol, 2 to 4 parts by weight of initiator and 0.1 to 1 part by weight of thixotropic agent, the premix C consists of 0.5 to 1 part by weight of initiator and 5 to 15 parts by weight of butyl acetate, and the premix D consists of 2 to 4 parts by weight of modified nano titanium dioxide and 5 to 15 parts by weight of butyl acetate.

In some embodiments of the present invention, the temperature of the heating in step 2) is 112-; preferably, in the step 2), the premix B is added dropwise within 1-4h, the temperature of the heat preservation reaction is 120-125 ℃, and the time of the heat preservation reaction is 0.5-2 h.

In some embodiments of the invention, in the step 3), the premix C is dripped within 10-30min, the temperature of the heat preservation reaction is 120-125 ℃, and the time of the heat preservation reaction is 2-4 h.

In some embodiments of the invention, in step 4), the distillation is carried out at 195 ± 3 ℃ under reduced pressure for 4-5h, and the pressure is-0.098 Mpa. The reduced pressure distillation at 195 ℃ is set to remove residual solvent as much as possible, so that the influence of butyl acetate in a system on a product is reduced, the residual butyl acetate can cause inaccurate test indexes of a final product, and certain influence is also caused on performance indexes of the product, such as flowability.

In some embodiments of the present invention, in step 4), the temperature increase is performed in a gradient temperature increase manner, and the specific process is as follows: after distillation at the normal pressure of 126-. If the continuous temperature rise is too high once, the risk that the kettle is flushed into a condensation pipe during reduced pressure distillation exists, so that the gradient temperature rise is adopted, and the safety is improved.

The invention also provides a serum separation gel, which comprises 900-1100 parts by weight of the resin for the serum separation gel as claimed in claim 1 or 2, 15-25 parts by weight of fumed silica and 40-50 parts by weight of a thixotropic agent.

In some embodiments of the invention, the thixotropic agent is triethanolamine. Compared with other thixotropic agents, the triethanolamine serving as the thixotropic agent can further improve product performance such as flowability and viscosity.

The invention also provides a preparation method of the serum separation gel, which comprises the following steps:

1) the resin for the serum separation gel is firstly stirred and mixed with the fumed silica under vacuum, and then the thixotropic agent is added for continuous vacuum stirring;

2) vacuumizing the materials uniformly stirred in the step 1) in a closed container, standing and defoaming to obtain the serum separation gel. In the step, the gas in the colloid is expanded and floated by utilizing the principle that the bubbles are expanded in vacuum until the surface of the colloid is cracked, so that the aim of defoaming is fulfilled.

In some embodiments of the invention, in step 1), the temperature of the stirring is less than or equal to 40 ℃; preferably, in step 2), the standing time is more than 12 h.

In some embodiments of the invention, in step 2), the vacuum degree of the vacuum pumping is-0.098 Mpa.

According to a preferred embodiment of the present invention, at least the following advantages are provided:

1. the thixotropic agent and the modified nano titanium dioxide are added into the resin for the serum separation gel, so that the centrifugal property, the fluidity and the hydrophobicity of a separation gel product are comprehensively improved, and the clinical service performances of the product, such as blood inclusion condition, oil drop probability, wire drawing condition and the like, are improved.

2. The serum separation gel prepared by the invention has good reversibility, and a good isolation layer is easy to form at low temperature; the risk of oil drops of the separating gel is low, the serum quality is good, and the separating gel can achieve a good serum isolating effect; the separation gel is not easy to separate out at the temperature of 55 ℃, and the separation gel is not easy to separate out in the blood collection tube even if the blood collection tube is inverted during the transportation process; the clinical effect and detection value of the serum separating gel are consistent with those of the Japanese imported separating gel, and the product performance is equivalent to that of the imported product, thereby being beneficial to expanding the domestic and foreign markets.

Detailed Description

The concept and technical effects of the present invention will be clearly and completely described below in conjunction with the embodiments to fully understand the objects, features and effects of the present invention. It is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments, and those skilled in the art can obtain other embodiments without inventive effort based on the embodiments of the present invention, and all embodiments are within the protection scope of the present invention.

Example 1

This example prepares a resin for serum separation gel, the formulation of which is shown in table 1:

TABLE 1

Wherein the modified nano titanium dioxide is prepared from HJB-516B modified titanium dioxide of Ohio chemical technology Co.

The specific preparation process of the resin for the serum separation gel is as follows:

1) adding the premix A into a reaction kettle, heating to 115 ℃, dropwise adding the premix B under the normal pressure state, keeping the temperature at 124 ℃ for reacting for 1h after dropwise adding is finished within 4 hours;

2) supplementing drops: and (3) adding the premix C, controlling the adding temperature at 124 ℃, finishing adding within 20 minutes, controlling the temperature at 124 ℃ after adding, and keeping the temperature for 3 hours.

3) And (3) distillation: adding premix D before distillation, starting heating, distilling at normal pressure of 126 ℃ for 3.5-4h, starting gradient heating to 160 ℃, 170 ℃, 185 ℃, starting vacuum reduced pressure distillation after heating to 185 ℃, gradually heating to 195 +/-3 ℃, preserving heat for 4.5h, cooling to below 120 ℃ after distillation, obtaining resin for serum separation gel, discharging the resin from the bottom of a kettle, containing, and transferring to a blending zone for blending the separation gel.

This example also prepared a serum separation gel having the material formulation shown in table 2:

TABLE 2

The specific preparation process of the serum separation gel is as follows:

1) blending: adding fumed silica into the obtained resin for serum separation gel, uniformly dispersing on a power mixer under vacuum and cooling conditions, adding thixotropic agent, uniformly dispersing, and controlling the stirring temperature to be below 40 ℃;

2) vacuum defoaming: and pumping the stirred separation gel into a closed container to be in high vacuum, standing for 12h for defoaming, and thus obtaining the serum separation gel.

Table 3 shows the comparison of the performances of the serum separation gel of example 1 and the Japanese imported separation gel (manufacturer: Japanese ponding).

TABLE 3

Centrifugal force/turnover rate: the turnover rate of the separation rubber is tested by using a corresponding centrifugal force at the low temperature of 10 ℃.

Oil drop probability: the blood is collected at normal temperature for 30min, and then centrifuged under 1600Xg × 5 min.

As can be seen from Table 3, the overall performance of the serum separation gel of example 1 is considered to be comparable to that of the Japanese imported separation gel, in terms of all properties.

The embodiments of the present invention have been described in detail, but the present invention is not limited to the embodiments, and various changes can be made without departing from the gist of the present invention within the knowledge of those skilled in the art. Furthermore, the embodiments of the present invention and the features of the embodiments may be combined with each other without conflict.