CN111297800A - Ion exchange fiber chloroquine suspension and preparation method thereof - Google Patents
Ion exchange fiber chloroquine suspension and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an ion exchange fiber chloroquine suspension and a preparation method thereof. The ion exchange fiber chloroquine suspension comprises the following components: 20-100 g/L of chloroquine or chloroquine derivatives, 10-150 g/L of strong acid type cation exchange fibers, 10-30 g/L of flavoring agents, 0.01-0.1 g/L of complexing agents and the balance of deionized water. The invention develops and obtains the ion exchange fiber chloroquine suspension sustained-release drug delivery system for the first time to prepare the chloroquine oral liquid, overcomes the defects of the traditional chloroquine tablets, injection and other dosage forms and the defect of unstable blood concentration of the common oral liquid, and ensures that the drug is easier to absorb and more convenient to swallow. The suspension has good mouthfeel, high patient compliance and small side effect, and can be used as a medicament for resisting viruses, treating rheumatoid arthritis, systemic lupus erythematosus and other autoimmune diseases in daily life.
Description
Technical Field
The invention belongs to the technical field of medicines. More particularly, relates to an ion exchange fiber chloroquine suspension and a preparation method thereof.
Background
For a long time, chloroquine has been used clinically as a first-line antimalarial drug, and its use has been reduced by the emergence of drug-resistant plasmodium. In addition, chloroquine has a mild immunosuppressive effect and is therefore used for the treatment of rheumatoid arthritis, systemic lupus erythematosus and other autoimmune diseases. The lysosome property of chloroquine enables the chloroquine to specifically act on lysosomes after entering cells, so that the pH in lysosomes is increased, the binding capacity of the chloroquine with autophagosomes is lost, and the inhibitory effect on autophagy is exerted. In addition, chloroquine has a broad-spectrum antiviral effect, has a good inhibition effect on HIV-1, influenza B virus, hepatitis A virus and SARS-related coronavirus, particularly has a strong inhibition capability on the novel coronavirus 2019-CoV, and is written in a novel coronavirus pneumonia diagnosis and treatment scheme (trial sixth edition).
At present, chloroquine medicines on the market are mainly in the forms of injection and tablets, however, the injection is generally used in professional institutions such as hospitals and the like and mainly treats acute and severe patients; the tablet has the defects of low bioavailability, poor drug stability, small distribution area in gastrointestinal tracts, high irritation, poor fluidity, uneven size, difficulty in dividing or coating, long disintegration time, low dissolution speed, high dosage and the like, and directly influences the quality and curative effect of the drug.
Oral liquid sustained release formulations are heterogeneous depot formulations formed by dispersing sustained release drug particles in a liquid medium. The fluidity of the medicine in the suspension is good, and the dosage of the oral medicine can be adjusted by patients at any time according to the disease requirements. After oral administration, the distribution area of the gastrointestinal tract is large, and the stimulation to the gastrointestinal tract is small. At the same time, it is less affected by the gastric emptying rate, which can reduce the differences between individuals, maintain the stability of blood drug levels, and reduce the risk of the patient taking the drug.
However, as chloroquine is absorbed in the intestinal tract more rapidly, in order to maintain the blood concentration balance for a long time and reduce the risk of instantaneous abnormal rise of the blood concentration, the chloroquine medicines generally adopt a tablet dosage form at present, the research on the chloroquine oral liquid sustained-release preparation is very limited at present, and no chloroquine oral liquid type related product is reported.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides an ion exchange fiber chloroquine suspension and a preparation method thereof. The invention develops a lower-concentration ion exchange fiber chloroquine administration system for the first time, not only overcomes the defects of a solid preparation, but also solves the problem of large blood concentration fluctuation of a conventional tablet, and the prepared chloroquine oral liquid preparation has good taste, improves the compliance of patients, has small side effect, can be used as an antiviral sustained-release oral liquid for daily use, and can also be used as a medicament for treating rheumatoid arthritis, systemic lupus erythematosus and other autoimmune diseases.
The invention aims to provide ion exchange fiber chloroquine suspension.
The invention also aims to provide a preparation method of the ion exchange fiber chloroquine suspension.
The above purpose of the invention is realized by the following technical scheme:
an ion exchange fiber chloroquine suspension comprises the following components: every 1000ml contains 20 g-100 g of chloroquine or chloroquine derivative, 10 g-150 g of cation exchange fiber, 10 g-30 g of flavoring agent, 0.01 g-0.1 g of complexing agent and the balance of deionized water.
The research of the invention finds that the cation exchange fiber can exchange with chloroquine cations to form a stable compound in a chemical bond form, and in an in vivo environment, the chloroquine cations are released by exchanging with cations such as in vivo sodium ions and the like without being influenced by acid and alkali in a receptor. The slow release suspension of the ion exchange fiber chloroquine compound prepared by the static administration method with lower dose of chloroquine compared with a tablet preparation not only overcomes the defects of the traditional chloroquine injection, the tablet and other preparations, but also solves the problem of large blood concentration fluctuation of the conventional oral liquid preparation, and further reduces the side effect on human bodies. The chloroquine ion exchange fiber system developed by the invention overcomes the defect of bitter taste of chloroquine, has good taste, is more easily accepted by combining with a flavoring agent with certain concentration, and is more suitable for daily use of people.
Furthermore, preferably, each 1000ml of the gel contains 50g to 70g of chloroquine or chloroquine derivatives, 40g to 60g of cation exchange fibers, 10g to 30g of flavoring agents, 0.04g to 0.06g of complexing agents and the balance of deionized water.
Furthermore, preferably, each 1000ml of the gel contains 60g of chloroquine or chloroquine derivative, 50g of ZB-1 strong acid type cation exchange fiber, 10g of flavoring agent, 0.05g of complexing agent and the balance of deionized water.
Preferably, the chloroquine derivative is one or more of chloroquine phosphate, hydroxychloroquine, chloroquine sulfate and chloroquine hydrochloride.
Preferably, the size of the cation exchange fiber is controlled to be 60-120 meshes, and preferably 80-120 meshes.
Preferably, the cation exchange fibers are ZB-1 strong acid type cation exchange fibers.
Preferably, the flavoring agent is one or more of xylitol, acesulfame potassium and erythritol.
Preferably, the complexing agent is one or more of EDTA, citric acid and tartaric acid.
As an alternative preferred scheme, the preparation method of the ion exchange fiber chloroquine suspension comprises the following steps:
s1, taking cation exchange fiber, repeatedly soaking the cation exchange fiber in water, ethanol, NaOH solution and HCl solution, performing suction filtration, washing the cation exchange fiber to be neutral by deionized water, and drying the cation exchange fiber for later use to obtain a raw material 1;
s2, adding the raw material 1, chloroquine or chloroquine derivatives into deionized water, and stirring at a constant temperature of 20-50 ℃ to obtain a solution 1;
s3, adding a flavoring agent and a complexing agent into deionized water to obtain a solution 2;
s4, mixing the solution 1 and the solution 2, stirring, and supplementing ionized water to obtain a suspension;
s5, after uniformly stirring, filling the suspension, and sealing.
Wherein, the concentration of the NaOH solution in the step S1 is preferably 0.5-2mol/L, and the concentration of the HCl solution is preferably 0.5-2 mol/L.
More preferably, the concentration of the NaOH solution in step S1 is 1.0mol/L and the concentration of the HCl solution is 1.0 mol/L.
Preferably, step S1 further includes a process of washing to neutral and then filtering with a filter screen.
Preferably, the screen is 60-120 meshes, and more preferably 80-120 meshes.
According to the invention, a large number of researches show that the strong-acid cation exchange fiber is filtered by using the screen with a specific mesh number, and the obtained ion exchange fiber can carry out drug loading on chloroquine more efficiently under the condition of certain drug loading time and temperature.
Preferably, in step S2, stirring is carried out at a constant temperature of 40-50 ℃ for 10-30 min.
Further, it is preferable that stirring is performed at a constant temperature of 45 ℃ for 20min in step S2.
The invention has the following beneficial effects:
the invention develops the chloroquine oral liquid for the first time, overcomes the defects of the traditional chloroquine tablets, injections and other dosage forms, and leads the medicine to be easier to absorb and more convenient to swallow.
The invention discloses a slow-release drug delivery system of a chloroquine suspension of ion exchange fibers, which overcomes the defect of unstable blood concentration of common oral liquid, and simultaneously, the prepared suspension has good taste and overcomes the problem of poor compliance of chloroquine bitter patients.
The invention researches and discovers that the ZB-1 strong acid type cation exchange fiber can exchange chloroquine cations generated by hydrolysis of chloroquine phosphate to form a stable compound in a chemical bond form, and in an in vivo environment, the chloroquine cations are released by exchanging the chloroquine cations with cations such as in vivo sodium ions and the like without being influenced by acid and alkali in a receptor. The slow release suspension of the ion exchange fiber chloroquine compound prepared by the static administration method with lower dose of chloroquine compared with a tablet preparation not only overcomes the defects of the traditional chloroquine injection, the tablet and other preparations, but also solves the problem of large blood concentration fluctuation of the conventional oral liquid preparation, and further reduces the side effect on human bodies. Can be used as daily antiviral drug for treating rheumatic arthritis, systemic lupus erythematosus and other autoimmune diseases.
In addition, in the preparation process of the ion exchange fiber chloroquine suspension, a suitable screen (preferably 80-120 meshes) for an ion exchange fiber chloroquine system is found, and a more efficient drug loading process is realized under the condition of shortening the drug loading time.
Drawings
FIG. 1 is a standard chromatogram of chloroquine phosphate;
FIG. 2 is a chromatogram of chloroquine phosphate in a test solution.
Detailed Description
The invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
EXAMPLE 1 preparation of ion-exchange fiber chloroquine suspension
The preparation method of the ion exchange fiber chloroquine suspension comprises the following steps:
(1) taking cation exchange fiber, respectively and sequentially and repeatedly soaking the cation exchange fiber by using water, ethanol, a 1.0mol/L NaOH solution and a 1.0mol/L HCl solution to convert the fiber into a hydrogen form, carrying out suction filtration, washing the fiber to be neutral by using deionized water, firstly carrying out primary screening by using a 60-mesh filter screen, then carrying out secondary screening on the ionic fiber passing through a screen by using an 80-mesh filter screen, taking the ionic fiber of the two-mesh filter screen which does not pass through the ionic fiber, and drying the ionic fiber for later use to obtain a raw material 1;
(2) weighing 50g of raw material 1 and 60g of chloroquine phosphate, adding 500ml of deionized water, and stirring at a constant temperature of 45 ℃ for 20min to obtain a solution 1;
(3) weighing 10g of xylitol and 0.05g of EDTA, and adding into 300ml of deionized water to obtain a solution 2;
(4) mixing the solution 1 and the solution 2, stirring uniformly at normal temperature, and supplementing ionized water to 1L to obtain suspension;
(5) after stirring uniformly, filling the suspension obtained in the step 4 with 10ml of each suspension, and sealing.
EXAMPLE 2 preparation of ion exchange fiber chloroquine suspension
The preparation method of the ion exchange fiber chloroquine suspension comprises the following steps:
(1) taking cation exchange fiber, respectively and sequentially and repeatedly soaking the cation exchange fiber by using water, ethanol, a 1.0mol/L NaOH solution and a 1.0mol/L HCl solution to convert the fiber into a hydrogen form, carrying out suction filtration, washing the fiber to be neutral by using deionized water, firstly carrying out primary screening by using an 80-mesh filter screen, then carrying out secondary screening on the ionic fiber passing through a screen by using a 100-mesh filter screen, taking the ionic fiber of the two-mesh filter screen which does not pass through the ionic fiber, and drying the ionic fiber for later use to obtain a raw material 1;
(2) weighing 50g of raw material 1 and 60g of chloroquine phosphate, adding 500ml of deionized water, and stirring at a constant temperature of 45 ℃ for 20min to obtain a solution 1;
(3) weighing 10g of xylitol and 0.05g of EDTA, and adding into 300ml of deionized water to obtain a solution 2;
(4) the same as example 1;
(5) the same as in example 1.
EXAMPLE 3 preparation of ion-exchange fiber chloroquine suspension
The preparation method of the ion exchange fiber chloroquine suspension comprises the following steps:
(1) taking cation exchange fiber, respectively and sequentially and repeatedly soaking the cation exchange fiber by using water, ethanol, a 1.0mol/L NaOH solution and a 1.0mol/L HCl solution to convert the fiber into a hydrogen form, carrying out suction filtration, washing the fiber to be neutral by using deionized water, firstly carrying out primary screening by using a 100-mesh filter screen, then carrying out secondary screening on the ionic fiber passing through a screen by using a 120-mesh filter screen, taking the ionic fiber of the two-mesh filter screen which does not pass through the filter screen, and drying for later use to obtain a raw material 1;
(2) weighing 50g of raw material 1 and 60g of chloroquine phosphate, adding 500ml of deionized water, and stirring at a constant temperature of 45 ℃ for 20min to obtain a solution 1;
(3) 10g of xylitol and 0.05g of EDTA were weighed and added to 300ml of deionized water to obtain solution 2.
(4) The same as example 1;
(5) the same as in example 1.
EXAMPLE 4 preparation of ion-exchange fiber chloroquine suspension
The preparation method of the ion exchange fiber chloroquine suspension comprises the following steps:
(1) taking cation exchange fiber, respectively and sequentially and repeatedly soaking the cation exchange fiber by using water, ethanol, a 1.0mol/L NaOH solution and a 1.0mol/L HCl solution to convert the fiber into a hydrogen form, carrying out suction filtration, washing the fiber to be neutral by using deionized water, firstly carrying out primary screening by using an 80-mesh filter screen, then carrying out secondary screening on the ionic fiber passing through a screen by using a 120-mesh filter screen, taking the ionic fiber of the two-mesh filter screen which does not pass through the secondary screen, and drying for later use to obtain a raw material 1;
(2) weighing 50g of raw material 1 and 60g of chloroquine phosphate, adding 500ml of deionized water, and stirring at a constant temperature of 45 ℃ for 20min to obtain a solution 1;
(3) 10g of xylitol and 0.05g of EDTA were weighed and added to 300ml of deionized water to obtain solution 2.
(4) The same as example 1;
(5) the same as in example 1.
EXAMPLE 5 preparation of ion-exchange fiber chloroquine suspension
The preparation method of the ion exchange fiber chloroquine suspension comprises the following steps:
(1) taking cation exchange fiber, respectively and sequentially and repeatedly soaking the cation exchange fiber by using water, ethanol, 2.0mol/L NaOH solution and 2.0mol/L HCl solution to convert the fiber into a hydrogen form, carrying out suction filtration, washing the fiber to be neutral by using deionized water, firstly carrying out primary screening by using a 100-mesh filter screen, then carrying out secondary screening on the ionic fiber passing through a screen by using a 120-mesh filter screen, taking the ionic fiber of the two-mesh filter screen which does not pass through the filter screen, and drying the ionic fiber for later use to obtain a raw material 1;
(2) weighing 150g of raw material 1 and 100g of hydroxychloroquine, adding 500ml of deionized water, and stirring at a constant temperature of 50 ℃ for 20min to obtain a solution 1;
(3) 30g of xylitol and 0.04g of EDTA are weighed and added to 300ml of deionized water to obtain a solution 2.
(4) The same as example 1;
(5) the same as in example 1.
EXAMPLE 6 preparation of ion-exchange fiber chloroquine suspension
The preparation method of the ion exchange fiber chloroquine suspension comprises the following steps:
(1) taking cation exchange fiber, respectively and sequentially and repeatedly soaking the cation exchange fiber by using water, ethanol, 0.5mol/L NaOH solution and 0.5mol/L HCl solution to convert the fiber into a hydrogen form, carrying out suction filtration, washing the fiber to be neutral by using deionized water, firstly carrying out primary screening by using an 80-mesh filter screen, then carrying out secondary screening on the ionic fiber passing through a screen by using a 120-mesh filter screen, taking the ionic fiber of the two-screen filter screen which does not pass through, and drying for later use to obtain a raw material 1;
(2) weighing 10g of raw material 1 and 20g of chloroquine sulfate, adding 500ml of deionized water, and stirring at a constant temperature of 20 ℃ for 20min to obtain a solution 1;
(3) 10g of xylitol and 0.06g of EDTA were weighed and added to 300ml of deionized water to obtain solution 2.
(4) The same as example 1;
(5) the same as in example 1.
EXAMPLE 7 ion-exchange fiber chloroquine suspension Performance testing
The ion exchange fiber chloroquine suspensions prepared in examples 1 to 6 were used as the study subjects, and the irritancy, bitterness and acceptability after trial were scored, respectively. The trial is carried out, the ion exchange fiber chloroquine suspension prepared in the embodiment 1-6 is divided into 6 groups, 5 persons in each group are selected for testing, the stimulation is graded from 1 grade to 10 grades, and the higher the grade is, the stronger the stimulation is; the bitter taste is divided into 1 to 10, and the higher the number is, the stronger the bitter taste is; the acceptability degree is from 1 point to 10 points, the higher the point is, the stronger the acceptability degree is, the average point is calculated, and the final trial statistical result is shown in table 1.
TABLE 1 ion exchange fiber chloroquine suspension Performance test
| Group of | Irritation property | Bitter taste | Degree of acceptance |
| Example 1 | 1.2 | 1.1 | 9.1 |
| Example 2 | 1.3 | 1.0 | 9.3 |
| Example 3 | 1.1 | 1.1 | 9.5 |
| Example 4 | 1.1 | 1.2 | 9.1 |
| Example 5 | 2.1 | 2.0 | 8.6 |
| Example 6 | 1.2 | 1.3 | 9.2 |
The results in table 1 show that the ion exchange fiber chloroquine suspension is mild, non-irritating, good in taste, high in receivable degree and good in market popularization value.
Example 8 testing of the Effect of mesh size on the drug loading Capacity of ion exchange fibers
1. Method for measuring chloroquine phosphate content
Weighing 1ml chloroquine phosphate solution, adding 9ml sodium hexanesulfonate solution (0.007mol/L), stirring and mixing uniformly, and quantitatively diluting to obtain a chloroquine phosphate solution of 0.1mg in each lml, thus obtaining a test solution. The obtained test solution was passed through a 0.45 μm filter and analyzed by HPLC. Precisely weighing 10mg of chloroquine phosphate reference substance, placing the chloroquine phosphate reference substance in a 10ml volumetric flask, adding sodium hexanesulfonate solution (0.007mol/L) to a constant volume to scale marks, and obtaining 1mg/ml reference substance stock solution. Accurately transferring 0.7ml, 0.8ml, 1ml, 1.2ml and 1.3ml of stock solutions into a 10ml volumetric flask, adding a mobile phase to a constant volume to scale marks to obtain a standard working solution with a relevant concentration, and drawing a standard working curve by passing the prepared standard working solution through a 0.45-micrometer filter membrane with the concentration of the chloroquine phosphate standard working solution as a horizontal coordinate and the peak area of the chloroquine phosphate as a vertical coordinate. Respectively injecting 10 mul of chloroquine phosphate series standard working solution and test solution into a high performance liquid chromatograph, analyzing according to chromatographic conditions specified by liquid chromatographic reference conditions, and recording peak areas, wherein the response value of the test solution is within the range of a standard curve. And (4) according to the retention time of the standard substance, determining the quality and quantifying by an external standard method. Chromatograms of the chloroquine phosphate standard substance and the test solution are respectively shown in figure 1 and figure 2.
The content of chloroquine phosphate in the test solution is calculated according to the formula (1):
X＝C1/C2×100％ (1)
in the formula: x-content designation, unit%; c1-content detected (mg/ml); c2-theoretical content (mg/ml); two significant decimal places are reserved in the calculation result.
2. The drug loading capacity detection method comprises the following steps:
selecting a 60-80 mesh filter screen, an 80-100 mesh filter screen, a 100-120 mesh filter screen and a 120 mesh filter screen to filter the ion exchange fibers respectively, and testing the drug loading capacity of the filtered ion exchange fibers: adding 60g of chloroquine phosphate and 50g of ion exchange fiber into 500mL of aqueous solution, and adding water to supplement the solution to 1000 mL; and (3) in a constant-temperature water bath at 45 ℃, stirring for 20min, determining the concentration of chloroquine phosphate by using the chloroquine phosphate content determination method, calculating the exchange drug quantity Q of the fiber according to the formula (2), and calculating the drug utilization rate E according to the formula (3):
Q＝(C0-Ct)V/WF(2)
E＝(C0-Ct)/C0(3)
wherein Q is the drug loading rate when the fiber is balanced; e is the utilization rate of the drug in equilibrium; c0(mg.mL-1) Is the initial concentration of chloroquine phosphate; ct(mg.mL-1) Is the equilibrium final concentration of chloroquine phosphate; v (mL) is the volume of the solution; wF(mg) is the mass of fiber added.
2. As a result:
the results are shown in table 2, the sizes of the sieve pores are continuously reduced along with the increase of the mesh number of the sieve pores, the particle size of the sieved ionic fiber is gradually reduced, the final concentration of chloroquine phosphate in the solution is continuously reduced along with the reduction of the particle size, and higher equilibrium drug utilization rate and equilibrium drug loading amount are simultaneously shown, but the difficulty of solid-liquid separation is gradually increased along with the reduction of the particle size of the fiber, and compared with 80-100 mesh fibers, 100-plus-sieve fibers and 120-mesh fibers, the difference between the drug utilization rate and the equilibrium drug loading amount of the 80-100 mesh fibers and the 100-plus-sieve fibers and the difference between the drug utilization rate and the equilibrium drug loading amount of the 120-mesh fibers are found to be not large, the difficulty of.
TABLE 2 mesh number versus drug loading capacity test results for ion exchange fibers (concentration replicate determination by triplicate averages)
EXAMPLE 9 drug Release test of ion-exchange fiber chloroquine suspensions
1. The detection method comprises the following steps:
selecting 100mL of ion exchange fiber (with the particle size of 80-100 meshes) obtained by secondary filtration of 80-mesh and 100-mesh screens and chloroquine loaded compound to carry out a drug release experiment, wherein the release experiment conditions are as follows: 900mL0.15mol.L-1NaCl as the dissolution medium was sampled every 15min at 37 ℃ and 50rpm, and the chloroquine phosphate concentration was measured (same method as in example 8). The concentration is repeatedly measured for three times, and the average value is taken, and the initial chloroquine concentration is 6.3mg-1。
2. As a result:
the results are shown in table 3, and the analysis of the obtained data shows that the ion exchange fiber chloroquine compound has a remarkable slow release effect in a NaCl solution with a certain concentration, wherein the release speed is higher in the first hour, the release speed is gradually reduced in the second hour, and the equilibrium concentration of the release is reached in about 2 hours.
TABLE 3 result of drug release from ion-exchange fiber chloroquine suspension
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. An ion exchange fiber chloroquine suspension is characterized by comprising the following components: 20-100 g/L of chloroquine or chloroquine derivatives, 10-150 g/L of cation exchange fibers, 10-30 g/L of flavoring agents, 0.01-0.1 g/L of complexing agents and the balance of deionized water.
2. The suspension according to claim 1, wherein 50-70 g/L of chloroquine or chloroquine derivatives, 40-60 g/L of cation exchange fibers, 10-30 g/L of flavoring agents, 0.04-0.06 g/L of complexing agents and the balance of deionized water.
3. The suspension according to claim 1, wherein the chloroquine derivative is one or more of chloroquine phosphate, hydroxychloroquine, chloroquine sulfate, chloroquine hydrochloride.
4. The suspension according to any one of claims 1 to 3, wherein the size of the cation exchange fibers is controlled to be 60 to 120 mesh.
5. The suspension according to any of claims 1 to 3, wherein the cation exchange fibres are ZB-1 strongly acidic cation exchange fibres.
6. The suspension according to claim 1, wherein the flavoring agent is one or more of xylitol, acesulfame potassium, erythritol.
7. The suspension according to claim 1, wherein the complexing agent is one or more of EDTA, citric acid, tartaric acid.
8. A process for the preparation of a suspension according to any one of claims 1 to 3, comprising the following steps:
s1, taking cation exchange fiber, sequentially soaking the cation exchange fiber in water, ethanol, a NaOH solution and an HCl solution, carrying out suction filtration, washing the cation exchange fiber to be neutral by using deionized water, and drying the cation exchange fiber for later use to obtain a raw material 1;
s2, adding the raw material 1 and chloroquine or chloroquine derivatives into deionized water, and stirring at a constant temperature of 20-50 ℃ to obtain a solution 1;
s3, adding a flavoring agent and a complexing agent into deionized water to obtain a solution 2;
s4, mixing the solution 1 and the solution 2, stirring, and supplementing ionized water to obtain a suspension;
s5, after uniformly stirring, filling the suspension, and sealing.
9. The method of claim 6, wherein the concentration of the NaOH solution in step S1 is 0.5-2mol/L, and the concentration of the HCl solution is 0.5-2 mol/L.
10. The method of claim 6, wherein the step S1 further comprises the steps of washing to neutral, and filtering with a filter screen; the screen is 60 ~ 120 meshes.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829115A (en) * | 2009-03-09 | 2010-09-15 | 上海交通大学医学院附属仁济医院 | Application of chloroquine compound or salt thereof in preparation of medicament for treating acute leukemia |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101829115A (en) * | 2009-03-09 | 2010-09-15 | 上海交通大学医学院附属仁济医院 | Application of chloroquine compound or salt thereof in preparation of medicament for treating acute leukemia |
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| Title |
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| 车鑫: "《潜在药用辅料离子交换纤维的性质及载药机制研究》", 《中国博士学位论文全文数据库 工程科技Ⅰ辑》 * |
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| WO2022006946A1 (en) * | 2020-07-08 | 2022-01-13 | 江苏四环生物制药有限公司 | Ibuprofen iatric fiber suspension and preparation method therefor |
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