C18 resin coated with polyethylene glycol and preparation method thereof

Abstract

A preparation method of C18 resin coated with polyethylene glycol comprises the following steps that 1, a C18 resin column is pretreated, absolute ethyl alcohol and deionized water sequentially flow through the C18 resin column through an injector, and then the C18 resin column is blow-dried; preparing a polyethylene glycol solution by using deionized water; 2, enabling a polyethylene glycol solution to flow through the C18 resin column pretreated in the step 1, and enabling deionized water to flow through the C18 resin column; and step 3, enabling the polyethylene glycol solution to flow through the C18 resin column, and enabling deionized water to flow through the C18 resin column to obtain the C18 resin column coated with polyethylene glycol. The C18 resin coated with polyethylene glycol prepared by the invention can be used for purifying Tc-99m in the process of producing Tc-99m by bombarding a Mo-100 target by an accelerator, so that the Tc-99m is separated from impurities.

Description

Technical Field

[0001] The present invention belongs to the field of chemical technology, relates to the technology for preparing separation resins, and particularly relates to a C18 resin coated with polyethylene glycol and a preparation method thereof. Background Art

[0002] Nuclear medicine uses radiation to diagnose or treat specific organs of a person. The use of radioactive isotopes is a routine operation in hospital diagnosis and treatment. More than 10,000 hospitals worldwide use radioactive isotopes, and about 90% of them are used for diagnosis. The most commonly used radioactive nuclide in diagnosis is technetium-99m (Tc-99m), which accounts for about 85% of all nuclear medicine diagnostic scans globally.

[0003] The current main source of Tc-99m is the production of molybdenum-99 (Mo-99) by irradiating uranium-235 in a reactor, and then preparing a Mo-99 / Tc-99m generator from molybdenum-99 (Mo-99). Tc-99m is obtained by eluting the generator, and about 95% of Tc-99m is obtained in this way; in contrast, the technical route for producing Tc-99m by a cyclotron is in the research stage and has not been commercially applied yet.

[0004] The advantage of producing Tc-99m by a cyclotron is that it does not require a reactor, can directly irradiate molybdenum-100 with protons to obtain Tc-99m, does not require the preparation of a Mo-99 / Tc-99m generator, and can be produced on demand. There are mainly four separation and purification methods for producing Tc-99m by a cyclotron: column chromatography separation method, thermal chromatography separation method, extraction method, and precipitation method. Among them, the column chromatography separation method has a simple process and is easy to automate, and is widely used.

[0005] The existing column chromatography separation method mainly uses anion exchange resins or polyethylene glycol resins. The advantage of using anion exchange resins for the separation and purification of Tc-99m is that they have a good retention effect on Tc-99m, but correspondingly, it is difficult to elute Tc-99m, and high-concentration acids or cationic organic reagents are required for elution, increasing subsequent processing steps and resulting in a low yield of the final product. The advantage of using polyethylene glycol resins is that they have a good retention effect, simple elution, and a relatively high yield of the final product. However, the disadvantage is that the existing resins are not easily obtained or are expensive, increasing the production cost. Summary of the Invention

[0006] In view of the above defects existing in the prior art, the present invention discloses a C18 resin coated with polyethylene glycol and a preparation method thereof.

[0007] The preparation method of the C18 resin coated with polyethylene glycol according to the present invention includes the following steps:

[0008] Step 1. Pretreat the C18 resin column. Sequentially pass anhydrous ethanol and deionized water through the C18 resin column using a syringe, and then dry it; Prepare a 4 - 8% wt polyethylene glycol solution with deionized water.

[0009] Step 2. Pass the polyethylene glycol solution through the pretreated C18 resin column in Step 1, and then pass deionized water through the C18 resin column.

[0010] Step 3. Repeat Step 2 one to two times.

[0011] Preferably, the volume - mass ratio of the anhydrous ethanol, deionized water to all the C18 resin in the C18 resin column in Step 1 is 1 mL: 0.05 - 0.1 g.

[0012] Preferably, the volume - mass ratio of the polyethylene glycol solution to all the C18 resin in the C18 resin column in Step 2 is 5 mL: 0.05 - 0.1 g.

[0013] Preferably, the molecular weight of the polyethylene glycol is 2000 to 6000.

[0014] Preferably, air drying is used in Step 1.

[0015] The present invention also discloses a C18 resin coated with polyethylene glycol, which is prepared by the method described in any one of the above.

[0016] The present invention prepares a new separation resin obtained by coating C18 resin with polyethylene glycol, which can be used for the purification of Tc - 99m in the production of Tc - 99m by bombarding a Mo - 100 target with an accelerator, realizing the separation of Tc - 99m from impurities; The preparation process of the present invention is simple, the raw materials are cheap, and the preparation price is relatively low compared with polyethylene glycol - based resins, thus reducing the production cost during the purification of Tc - 99m; And this resin has good selectivity for Tc - 99m and good removal effect on impurity elements, and can economically and efficiently realize the separation and purification of Tc - 99m. Brief Description of the Drawings

[0017] Figure 1 Shown is a schematic diagram of a specific embodiment of the method for preparing the C18 resin coated with polyethylene glycol according to the present invention. Detailed Embodiments

[0018] To more intuitively and clearly describe the specific details of the technical solution of the present invention, the following will be described in detail in combination with specific examples and example drawings.

[0019] To make the objectives, technical solutions and advantages of the present invention more clear, the following will clearly and completely elaborate on the technical solutions of the present invention in conjunction with the specific embodiments of the present invention and the corresponding drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0020] As Figure 1 shown, the present invention is for preparing C18 resin coated with polyethylene glycol. The applicable molecular weight of polyethylene glycol is between 2000 and 6000. The C18 resin column selected as the processing matrix can be a common commercially available product.

[0021] The preparation method of the separation resin is as Figure 1 shown. It is prepared in three steps to obtain the C18 resin coated with polyethylene glycol described in the present invention.

[0022] Step 1. Pretreat the C18 resin column. Sequentially pass 10 mL of absolute ethanol and 10 mL of deionized water through the C18 resin column with a syringe, and then blow 10 mL of air; prepare a 6% wt polyethylene glycol solution with deionized water;

[0023] The purpose of flowing absolute ethanol and deionized water into the C18 resin column is to activate the C18 resin. After activation, blow air to dry the C18 resin.

[0024] When activating, the volume-mass ratio of absolute ethanol, deionized water to all the C18 resin in the C18 resin column is 1 mL: 0.05 - 0.1 g;

[0025] Configure the concentration of the polyethylene glycol solution with the lower limit being able to effectively adsorb pertechnetate, set at above 4%. Theoretically, the higher the concentration of the polyethylene glycol solution, the better the adsorption effect. However, the adsorption effect does not increase linearly with the concentration, and the solubility of polyethylene glycol with a molecular weight of 2000 to 6000 is less than 100 g. Therefore, set the solubility of polyethylene glycol in the range of 4 - 8%;

[0026] Step 2. Use a peristaltic pump to pass 50 mL of 6% wt polyethylene glycol solution through the C18 resin column pretreated in Step 1, and then pass 50 mL of deionized water through the C18 resin column;

[0027] The volume-mass ratio of the polyethylene glycol solution to all the C18 resin in the C18 resin column is 5 mL: 0.05 - 0.1 g;

[0028] Step 3. Repeat Step 2 one to two times.

[0029] Repeating step 2 can avoid the situation that some C18 resin may not be combined with polyethylene glycol during a single flow-through, and enhance the reaction effect of the C18 column.

[0030] Tc-99m exists in the solution in the form of pertechnetate ion (99mTcO4-), and polyethylene glycol has selectivity for 99mTcO4-. Therefore, polyethylene glycol-based resin can be used to separate and purify Tc-99m. In the present invention, C18 resin is used as the matrix, polyethylene glycol is dissolved in deionized water and slowly flows through the C18 resin. Since polyethylene glycol and C18 resin have positive and negative charge ion groups respectively, polyethylene glycol is combined with the C18 resin by means of van der Waals force or hydrogen bond, etc., so as to obtain polyethylene glycol-coated C-18 resin. This resin can selectively adsorb pertechnetate ion through the polyethylene glycol on its surface, thus realizing the separation and purification of Tc-99m.

[0031] Specific Example 1: Use polyethylene glycol with a molecular weight of 2000 (PEG-2000) to prepare 100 mL of 6% wt polyethylene glycol solution with deionized water.

[0032] Prepare 0.5 g of C18 resin with a mesh number of 50 - 100, and place it in a chromatographic column to form a C18 resin column as the matrix. Use a syringe to take 10 mL of anhydrous ethanol and inject it into the C18 resin column, then take 10 mL of deionized water and inject it into the C18 resin column, and then blow 10 mL of air into the C-18 resin column. Next, use a peristaltic pump to flow 50 mL of 6% wt polyethylene glycol solution, 50 mL of deionized water, 50 mL of 6% wt polyethylene glycol solution and 50 mL of deionized water through the C-18 resin column in sequence to obtain C18 resin (PEG-2000) coated with polyethylene glycol. This resin is used for the separation experiment of producing Tc-99m from a molybdenum target. The decontamination factor for Mo reaches 99.999%, and a qualified Tc-99m product is successfully obtained.

[0033] Example 2: Use polyethylene glycol with a molecular weight of 4000 (PEG-4000) to prepare 100 mL of 6% wt polyethylene glycol solution with deionized water. Prepare 0.5 g of C18 resin with a mesh number of 50 - 100, and place it in a chromatographic column to form a C18 resin column as the matrix.

[0034] Take 10 mL of absolute ethanol with a syringe and inject it into the C18 resin column. Then take 10 mL of deionized water and inject it into the C18 resin column. Next, blow 10 mL of air into the C-18 resin column. Subsequently, use a peristaltic pump to flow 50 mL of 6% wt polyethylene glycol solution, 50 mL of deionized water, 50 mL of 6% wt polyethylene glycol solution, and 50 mL of deionized water through the C-18 resin column in sequence to obtain C18 resin (PEG-4000) coated with polyethylene glycol. Use this resin for the separation experiment of producing Tc-99m from a molybdenum target. The decontamination factor for Mo reaches 99.999%, and a qualified Tc-99m product is successfully obtained.

[0035] The foregoing are various preferred embodiments of the present invention. If the preferred implementation manners in each preferred embodiment are not obviously self-contradictory or premised on a certain preferred implementation manner, each preferred implementation manner can be arbitrarily superimposed and combined for use. The specific parameters in the embodiments are only for clearly expressing the inventor's invention verification process and are not used to limit the patent protection scope of the present invention. The patent protection scope of the present invention still depends on its claims. Any equivalent structural changes made by using the content of the specification and drawings of the present invention should, by the same token, be included in the protection scope of the present invention.

Claims

1. A method for preparing a C18 resin coated with polyethylene glycol, characterized in that , including the following steps: Step 1. Pre-treat the C18 resin column by passing anhydrous ethanol and deionized water through the C18 resin column in sequence with a syringe, and then blow dry; prepare a 4-8%wt polyethylene glycol solution with deionized water; Step 2. Pass the polyethylene glycol solution through the C18 resin column pretreated in step 1, and then pass deionized water through the C18 resin column; Step 3. Repeat step 2 one or two times.

2. The method for preparing a C18 resin coated with polyethylene glycol as claimed in claim 1, characterized in that: The volume mass ratio of the anhydrous ethanol, deionized water and all the C18 resin in the C18 resin column in step 1 is 1 ml: 0.05-0.1 g.

3. The method for preparing the C18 resin coated with polyethylene glycol as claimed in claim 1, characterized in that: The volume mass ratio of the polyethylene glycol solution and the total C18 resin in the C18 resin column in step 2 is 5 ml: 0.05-0.1 g.

4. The method for preparing the C18 resin coated with polyethylene glycol as claimed in claim 1, characterized in that: The molecular weight of the polyethylene glycol is 2000 to 6000.

5. The method for preparing the C18 resin coated with polyethylene glycol as claimed in claim 1, characterized in that: In the step 1, air drying is adopted.

6. A C18 resin coated with polyethylene glycol, characterized in that: The method is prepared by any one of claims 1 to 5.

Images