Preparation method of medicinal aluminum chloride hexahydrate with uniform quality

Abstract

The invention discloses a preparation method of medicinal aluminum chloride hexahydrate with uniform quality, which comprises the following steps: dissolving industrial grade aluminum chloride hexahydrate in deionized water, adjusting the pH value to 1-2, adding a composite flocculant, stirring and flocculating, and sequentially filtering, concentrating and crystallizing in stages, and centrifuging to obtain the medicinal aluminum chloride hexahydrate. The preparation method of the aluminum chloride hexahydrate can realize uniformity and high content of an aluminum chloride product, and is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical excipients, and in particular to a method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality. Background Art

[0002] Aluminum chloride hexahydrate is a white crystal that undergoes hydrolysis in water to generate aluminum hydroxide and hydrochloric acid, which can be used as a Lewis acid or Lewis base. In organic solvents, aluminum chloride can convert organic molecules with weak electron affinity into active substances with strong electron affinity. Therefore, it is widely used in organic synthesis, chemicals and medicine. Its content and quality uniformity are important factors affecting catalytic alkylation, construction of carbon-carbon bonds and realization of chemical reduction reactions.

[0003] However, during the preparation of aluminum chloride hexahydrate, HCl will volatilize when heated, and the remaining Al(OH)3 is unstable and decomposes to form Al2O3 when heated. Therefore, the quality of the finished product is often uneven due to different heating intensities, and the content is difficult to exceed 98.5%, which is difficult to meet the quality requirements of pharmaceutical companies for high-content pharmaceutical excipient aluminum chloride hexahydrate. Summary of the invention

[0004] In order to solve at least one problem existing in the above-mentioned prior art, the present invention provides a method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality, which can achieve uniformity and high content of aluminum chloride products and is suitable for industrial production.

[0005] In order to achieve the above-mentioned purpose, the present invention adopts the following technical scheme: a method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality, which comprises dissolving industrial-grade aluminum chloride hexahydrate in deionized water, adjusting the pH to 1-2, adding a composite flocculant, stirring and flocculating, and then filtering, concentrating and crystallizing in stages, and centrifuging to obtain pharmaceutical aluminum chloride hexahydrate.

[0006] Preferably, the method for preparing the medicinal aluminum chloride hexahydrate comprises the following specific steps:

[0007] Step 1, dissolving and flocculating: adding industrial grade aluminum chloride hexahydrate into deionized water, heating to 70-80°C to dissolve, adjusting the pH of the solution to 1-2, adding a composite flocculant made of a mixture of polyaluminum chloride and polyacrylamide into the solution, stirring for 20-30 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules;

[0008] Step 2, filtering: filtering the aluminum chloride aqueous solution with floccules to remove the floccules, to obtain an aluminum chloride aqueous solution;

[0009] Step 3, concentration: the aluminum chloride aqueous solution is concentrated in two stages: in the first stage, the solution is concentrated under reduced pressure quickly until crystallization occurs, and in the second stage, the concentration is slowed down to allow crystal growth. When the amount of evaporated water is 60-70% of the amount of deionized water used in step (1), the concentration is stopped to obtain an aluminum chloride hexahydrate mixed solution;

[0010] Step 4, cooling: continue to stir the aluminum chloride hexahydrate mixture and cool it to below 38° C. with cooling water;

[0011] Step 5, centrifugation: centrifuge the cooled aluminum chloride hexahydrate mixed solution for the first time, 20 to 40 minutes per centrifuge, remove the liquid, and obtain pharmaceutical aluminum chloride hexahydrate.

[0012] Preferably, the mass ratio of industrial-grade aluminum chloride hexahydrate to deionized water is 1:0.6-0.7. Too much deionized water will result in a thin solution, which is not conducive to flocculation. Too little deionized water will result in incomplete dissolution of the raw materials.

[0013] Preferably, the addition amount of the composite flocculant is 0.1-0.2% of the mass of aluminum chloride hexahydrate. Too much amount will increase the cost, and is not conducive to the further aggregation of particles, and the flocculation effect will become worse; too little amount will reduce the flocculation effect. Preferably, in the composite flocculant, the mass ratio of polyaluminum chloride to polyacrylamide is 1:0.8-1:1.2, preferably 1:1. In the composite flocculant, too much polyacrylamide will increase the cost, and is not conducive to the further aggregation of particles, and the flocculation effect is also poor; too little polyacrylamide will reduce the flocculation effect.

[0014] Preferably, the pressure of reduced pressure concentration is -0.095 to -0.1 MPa.

[0015] Preferably, the conditions for the rapid decompression concentration in the first stage are: pressure of -0.095 to -0.1 MPa, temperature of 65 to 70° C., and stirring speed of 15 to 20 r / min.

[0016] Preferably, the conditions for the second stage of slow decompression concentration are: pressure of -0.095 to -0.1 MPa, temperature of 55 to 65° C., and stirring speed of 10 to 15 r / min.

[0017] Preferably, the centrifugation further comprises, after the first centrifugation, uniformly spraying 10-12% hydrochloric acid on the surface of the solid material after the first centrifugation, and then performing a second centrifugation for 30-40 minutes / machine to remove the liquid.

[0018] Preferably, the amount of 10-12% hydrochloric acid used is 2-3% of the mass of the solid material after the first centrifugation.

[0019] Preferably, hydrochloric acid is used to adjust the pH value.

[0020] Preferably, the filtering filter element adopts a two-stage filter element.

[0021] Preferably, the filtering filter element adopts a two-stage filter element of 1μm filter element + 0.22μm filter element, which can increase the life of the sterilization filter element.

[0022] Preferably, when cooling, the temperature difference between the inlet and outlet of the cooling water is controlled at 5-10°C.

[0023] The beneficial effects of the present invention are as follows: 1. The preparation method of the present invention uses industrial-grade aluminum chloride hexahydrate as the main raw material, deionized water as the solvent, and a composite flocculant composed of polyaluminum chloride and polyacrylamide, so that the aluminum oxide particles remaining in the aluminum chloride raw material are aggregated and enlarged, which is beneficial to the filtration and removal of impurities; 2. By controlling the concentration in stages, the aluminum chloride is slowly precipitated in the crystallization kettle, and crystals with uniform particle size and shape are gradually formed; 3. By centrifugal dehydration and elution with 10-12% hydrochloric acid, the aluminum hydroxide remaining on the surface of the crystal is further removed; 4. The mother liquor generated by the preparation method of the present invention can be repeatedly used; 5. The preparation method of the present invention improves the uniformity and content of the aluminum chloride product by optimizing the refining conditions and controlling the refining process, and is suitable for industrial production. DETAILED DESCRIPTION

[0024] The following is a clear and complete description of the technical solutions in the implementation of the present invention. The described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without making creative work are within the scope of protection of the present invention. If the specific conditions are not specified in the embodiments, they are carried out according to the normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents, instruments, and components used, they are all conventional products that can be purchased commercially.

[0025] The quality requirements of pharmaceutical companies for high-content pharmaceutical excipient aluminum chloride hexahydrate are shown in Table 1.

[0026] The present invention uses industrial grade aluminum chloride hexahydrate as the main raw material.

[0027]

[0028] In addition, it should be noted that the AlCl3·6H2O content determined by the T / CSTM 00071-2019 standard is between 98.0% and 100.5%, and pharmaceutical customers will require the AlCl3·6H2O content to be higher than 98.0% on this basis. Generally, it must reach 98.5% or above to be qualified for shipment, so the standard indicator is 98.5-100.5%.

[0029] Example 1

[0030] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0031] Step 1, dissolving and flocculating: adding 25 kg of industrial grade aluminum chloride hexahydrate to 16 kg of deionized water, heating to 75°C to dissolve, adjusting the pH of the solution to 1-2 with hydrochloric acid, and then adding 25 g of a composite flocculant prepared by mixing polyaluminum chloride and polyacrylamide in a mass ratio of 1:1 to the solution, stirring for 20 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules;

[0032] Step 2, filtration: filtering the aluminum chloride aqueous solution with flocs through a two-stage filter element of 1 μm filter element + 0.22 μm filter element to remove the flocs, thereby obtaining an aluminum chloride aqueous solution;

[0033] Step 3, concentration: the aluminum chloride aqueous solution is concentrated in two stages: the first stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 70°C, and a stirring speed of 20 r / min, and the solution is rapidly concentrated under reduced pressure until crystallization occurs; and the second stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 65°C, and a stirring speed of 15 r / min, and the reduced pressure is slowed down and concentrated to allow crystals to grow. The amount of water evaporated is 10 kg, and the concentration is stopped. At this time, a large amount of material is precipitated to obtain an aluminum chloride hexahydrate mixed solution;

[0034] Step 4, cooling: turn off the heating and vacuum, keep the stirring speed of the aluminum chloride hexahydrate mixture at 15r / min, control the temperature difference of the cooling water inlet and outlet at 5-10°C, and turn off the cooling water and stirring when the temperature of the material in the kettle drops below 38°C;

[0035] Step 5, centrifugation: the cooled aluminum chloride hexahydrate mixed solution is centrifuged for the first time, 30 min / machine, the liquid is removed, and 17.0 kg of solid material after the first centrifugation is obtained. Then 340 g of 11.2% hydrochloric acid is evenly sprayed on the surface of the solid material after the first centrifugation, and then the second centrifugation is performed, 40 min / machine, and the liquid is removed to obtain medicinal aluminum chloride hexahydrate.

[0036] In addition, the mother liquor produced by the preparation method can be used repeatedly.

[0037] Example 2

[0038] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0039] Step 1, dissolving and flocculating: adding 25 kg of industrial grade aluminum chloride hexahydrate to 16 kg of deionized water, heating to 75°C to dissolve, adjusting the pH of the solution to 1-2 with hydrochloric acid, and then adding 25 g of a composite flocculant prepared by mixing polyaluminum chloride and polyacrylamide in a mass ratio of 1:1 to the solution, stirring for 20 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules;

[0040] Step 2, filtration: filtering the aluminum chloride aqueous solution with flocs through a two-stage filter element of 1 μm filter element + 0.22 μm filter element to remove the flocs, thereby obtaining an aluminum chloride aqueous solution;

[0041] Step 3, concentration: the aluminum chloride aqueous solution is concentrated in two stages: the first stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 70°C, and a stirring speed of 20 r / min, and the solution is rapidly concentrated under reduced pressure until crystallization occurs; and the second stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 65°C, and a stirring speed of 15 r / min, and the reduced pressure is slowed down and concentrated to allow crystals to grow. The amount of water evaporated is 10 kg, and the concentration is stopped. At this time, a large amount of material is precipitated to obtain an aluminum chloride hexahydrate mixed solution;

[0042] Step 4, cooling: turn off the heating and vacuum, keep the stirring speed of the aluminum chloride hexahydrate mixture at 15r / min, control the temperature difference of the cooling water inlet and outlet at 5-10°C, and turn off the cooling water and stirring when the temperature of the material in the kettle drops below 38°C;

[0043] Step 5, centrifugation: centrifuge the cooled aluminum chloride hexahydrate mixed solution for the first time, 40 min / machine, remove the liquid, and obtain pharmaceutical aluminum chloride hexahydrate.

[0044] Example 3

[0045] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0046] Step 1, dissolving and flocculating: adding 25 kg of industrial grade aluminum chloride hexahydrate to 16 kg of deionized water, heating to 75° C. to dissolve, adjusting the pH of the solution to 1-2 with hydrochloric acid, and then adding 25 g of a composite flocculant prepared by mixing polyaluminum chloride and polyacrylamide in a mass ratio of 1:0.8 to the solution, stirring for 20 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules;

[0047] The remaining steps are the same as those in Example 1.

[0048] Example 4

[0049] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0050] Step 1, dissolving and flocculating: adding 25 kg of industrial grade aluminum chloride hexahydrate to 16 kg of deionized water, heating to 75°C to dissolve, adjusting the pH of the solution to 1-2 with hydrochloric acid, and then adding 25 g of a composite flocculant prepared by mixing polyaluminum chloride and polyacrylamide in a mass ratio of 1:1.2 to the solution, stirring for 20 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules;

[0051] The remaining steps are the same as those in Example 1.

[0052] Example 5

[0053] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0054] Step 1, dissolving and flocculating: adding 25 kg of industrial grade aluminum chloride hexahydrate to 15 kg of deionized water, heating to 70°C to dissolve, adjusting the pH of the solution to 1-2 with hydrochloric acid, and then adding 37.5 g of a composite flocculant prepared by mixing polyaluminum chloride and polyacrylamide in a mass ratio of 1:1 to the solution, stirring for 20 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules;

[0055] Step 2, filtration: filtering the aluminum chloride aqueous solution with flocs through a two-stage filter element of 1 μm filter element + 0.22 μm filter element to remove the flocs, thereby obtaining an aluminum chloride aqueous solution;

[0056] Step 3, concentration: the aluminum chloride aqueous solution is concentrated in two stages: the first stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 65°C, and a stirring speed of 15 r / min, and the solution is rapidly concentrated under reduced pressure until crystallization occurs; and the second stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 55°C, and a stirring speed of 10 r / min, and the reduced pressure is slowed down and concentrated to allow crystals to grow. The amount of water evaporated is 10 kg, and the concentration is stopped. At this time, a large amount of material is precipitated to obtain an aluminum chloride hexahydrate mixed solution;

[0057] Step 4, cooling: turn off the heating and vacuum, keep the stirring speed of the aluminum chloride hexahydrate mixture at 10r / min, control the temperature difference of the cooling water inlet and outlet at 5-10°C, and turn off the cooling water and stirring when the temperature of the material in the kettle drops below 38°C;

[0058] Step 5, centrifugation: the cooled aluminum chloride hexahydrate mixed solution is centrifuged for the first time, 20 min / machine, the liquid is removed, and 17.2 kg of solid material after the first centrifugation is obtained. Then 430 g of 12% hydrochloric acid is evenly sprayed on the surface of the solid material after the first centrifugation, and then the second centrifugation is performed, 30 min / machine, and the liquid is removed to obtain medicinal aluminum chloride hexahydrate.

[0059] Example 6

[0060] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0061] Step 1, dissolving and flocculating: adding 25 kg of industrial grade aluminum chloride hexahydrate to 17.5 kg of deionized water, heating to 85°C to dissolve, adjusting the pH of the solution to 1-2 with hydrochloric acid, and then adding 50 g of a composite flocculant prepared by mixing polyaluminum chloride and polyacrylamide in a mass ratio of 1:1 to the solution, stirring for 20 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules;

[0062] Step 2, filtration: filtering the aluminum chloride aqueous solution with flocs through a two-stage filter element of 1 μm filter element + 0.22 μm filter element to remove the flocs, thereby obtaining an aluminum chloride aqueous solution;

[0063] Step 3, concentration: the aluminum chloride aqueous solution is concentrated in two stages: the first stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 68°C, and a stirring speed of 17 r / min, and the solution is rapidly concentrated under reduced pressure until crystallization occurs; and the second stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 60°C, and a stirring speed of 13 r / min, and the reduced pressure is slowed down and concentrated to allow crystals to grow. The amount of water evaporated is 12 kg, and the concentration is stopped. At this time, a large amount of material is precipitated to obtain an aluminum chloride hexahydrate mixed solution;

[0064] Step 4, cooling: turn off the heating and vacuum, keep the stirring speed of the aluminum chloride hexahydrate mixture at 13r / min, control the temperature difference between the inlet and outlet of the cooling water at 5-10°C, and turn off the cooling water and stirring when the temperature of the material in the kettle drops below 38°C;

[0065] Step 5, centrifugation: The cooled aluminum chloride hexahydrate mixed solution is centrifuged for the first time, 25 min / machine, and the liquid is removed to obtain 17.1 kg of solid material after the first centrifugation. Then 510 g of 10% hydrochloric acid is evenly sprayed on the surface of the solid material after the first centrifugation, and then the second centrifugation is performed, 35 min / machine, and the liquid is removed to obtain medicinal aluminum chloride hexahydrate.

[0066] Comparative Example 1

[0067] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0068] Step 1, dissolving and flocculating: add 25 kg of industrial grade aluminum chloride hexahydrate to 16 kg of deionized water, heat to 75°C to dissolve, then adjust the solution pH to 1-2 with hydrochloric acid, stir for 20 minutes, and let stand to form an aluminum chloride aqueous solution;

[0069] Step 2, filtration: filtering the aluminum chloride aqueous solution through a two-stage filter element of 1 μm filter element + 0.22 μm filter element to remove flocculation, thereby obtaining an aluminum chloride aqueous solution;

[0070] Step 3, concentration: the aluminum chloride aqueous solution is concentrated in two stages: the first stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 70°C, and a stirring speed of 20 r / min, and the solution is rapidly concentrated under reduced pressure until crystallization occurs; and the second stage is carried out under a pressure of -0.095 to -0.1 MPa, a temperature of 65°C, and a stirring speed of 15 r / min, and the reduced pressure is slowed down and concentrated to allow crystals to grow. The amount of water evaporated is 10 kg, and the concentration is stopped. At this time, a large amount of material is precipitated to obtain an aluminum chloride hexahydrate mixed solution;

[0071] Step 4, cooling: turn off the heating and vacuum, keep the stirring speed of the aluminum chloride hexahydrate mixture at 15r / min, control the temperature difference of the cooling water inlet and outlet at 5-10°C, and turn off the cooling water and stirring when the temperature of the material in the kettle drops below 38°C;

[0072] Step 5, centrifugation: the cooled aluminum chloride hexahydrate mixed solution is centrifuged for the first time, 30 min / machine, the liquid is removed, and 17.5 kg of solid material after the first centrifugation is obtained. Then 360 g of 11.2% hydrochloric acid is evenly sprayed on the surface of the solid material after the first centrifugation, and then a second centrifugation is performed, 40 min / machine, and the liquid is removed to obtain aluminum chloride hexahydrate.

[0073] Comparative Example 2

[0074] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0075] Step 1, dissolving and flocculating: adding 25 kg of industrial grade aluminum chloride hexahydrate to 16 kg of deionized water, heating to 75°C to dissolve, adjusting the pH of the solution to 1-2 with hydrochloric acid, and then adding 25 g of a composite flocculant prepared by mixing polyaluminum chloride and polyacrylamide in a mass ratio of 1:1 to the solution, stirring for 20 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules;

[0076] Step 2, filtration: filtering the aluminum chloride aqueous solution with flocs through a two-stage filter element of 1 μm filter element + 0.22 μm filter element to remove the flocs, thereby obtaining an aluminum chloride aqueous solution;

[0077] Step 3, concentration: the aluminum chloride aqueous solution is rapidly reduced in pressure and concentrated at a pressure of -0.095 to -0.1 MPa, a temperature of 70°C, and a stirring speed of 20 r / min until the solution crystallizes and the amount of evaporated water is 10 kg. The concentration is stopped, at which time a large amount of material is precipitated to obtain an aluminum chloride hexahydrate mixed solution;

[0078] Step 4, cooling: turn off the heating and vacuum, keep the stirring speed of the aluminum chloride hexahydrate mixture at 15r / min, control the temperature difference of the cooling water inlet and outlet at 5-10°C, and turn off the cooling water and stirring when the temperature of the material in the kettle drops below 38°C;

[0079] Step 5, centrifugation: the cooled aluminum chloride hexahydrate mixed solution is centrifuged for the first time, 30 min / machine, the liquid is removed, and 17.4 kg of solid material after the first centrifugation is obtained. Then 350 g of 11.2% hydrochloric acid is evenly sprayed on the surface of the solid material after the first centrifugation, and then a second centrifugation is performed, 40 min / machine, and the liquid is removed to obtain aluminum chloride hexahydrate.

[0080] Comparative Example 3

[0081] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0082] Step 1, dissolving and flocculating: add 25 kg of industrial grade aluminum chloride hexahydrate to 16 kg of deionized water, heat to 75°C to dissolve, then adjust the pH of the solution to 1-2 with hydrochloric acid, add 25 g of polyaluminum chloride flocculant to the solution, stir for 20 minutes, and let it stand to form an aluminum chloride aqueous solution with flocculation;

[0083] The remaining steps are the same as those in Example 1.

[0084] Comparative Example 4

[0085] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0086] Step 1, dissolving and flocculating: add 25 kg of industrial grade aluminum chloride hexahydrate to 16 kg of deionized water, heat to 75°C to dissolve, then adjust the pH of the solution to 1-2 with hydrochloric acid, then add 25 g of polyacrylamide flocculant to the solution, stir for 20 minutes, and let it stand to form an aluminum chloride aqueous solution with floccules;

[0087] The remaining steps are the same as those in Example 1.

[0088] Comparative Example 5

[0089] A method for preparing medicinal aluminum chloride hexahydrate, the specific steps are as follows:

[0090] Step 1, dissolving and flocculating: adding 25 kg of industrial grade aluminum chloride hexahydrate to 16 kg of deionized water, heating to 75°C to dissolve, adjusting the pH of the solution to 1-2 with hydrochloric acid, and then adding 25 g of a composite flocculant prepared by mixing polyaluminum chloride and polyacrylamide in a mass ratio of 1:0.7 to the solution, stirring for 20 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules;

[0091] The remaining steps are the same as those in Example 1.

[0092] The products prepared in the above Examples 1 to 6 and Comparative Examples 1 to 7 were tested, and the results are shown in Tables 2 and 3.

[0093] Table 2 Products prepared in Examples 1 to 6

[0094]

[0095] Table 3 Products prepared in Comparative Examples 1 to 7

[0096]

[0097] As can be seen from Tables 2 and 3 above, the present invention uses industrial-grade aluminum chloride hexahydrate as the main raw material, deionized water as the solvent, and a composite flocculant composed of polyaluminum chloride and polyacrylamide in a mass ratio of 1:0.8 to 1:1.2, so that the aluminum oxide particles remaining in the aluminum chloride raw material are aggregated and enlarged, which is conducive to the filtration and removal of insoluble impurities such as aluminum oxide and aluminum hydroxide, and has good clarity and no fluorescence. Compared with the raw material quality and Comparative Examples 1 to 5, the content of the medicinal aluminum chloride hexahydrate prepared by the present invention is greater than 98.5%, which can reach 99.7%, and the alkali metal and alkaline earth metal are reduced, the clarity is good, no fluorescence is generated, and the particle size is moderate and uniform; further, in Example 2, hydrochloric acid is not used for elution during centrifugal dehydration, and the alkali metal and alkaline earth metal are slightly higher, but no fluorescence phenomenon occurs; in Example 1 and Examples 3 to 6, hydrochloric acid is used for elution during centrifugal dehydration, and the alkali metal and alkaline earth metal are less, and the preparation method of Example 1 and Examples 3 to 6 can be preferred.

[0098] In Comparative Example 1, no flocculant is used for flocculation and impurity removal. Except for the moderate and uniform particle size, other important indicators are slightly improved, but the quality requirements of pharmaceutical companies for high-content pharmaceutical excipient aluminum chloride hexahydrate are not met; in Comparative Example 2, only the process parameters of the first stage rapid concentration are used, and the crystal growth conditions are lacking. The finished particles are small, the particle surface area is increased, and the attached water is difficult to remove by centrifugation, so the moisture content is high; in addition, if only the process parameters of the second stage slow concentration are used, the concentration time is increased, the energy consumption is increased, and the production efficiency is reduced; in Comparative Example 3, only polyaluminum chloride is used, and the formed The flocculated particles are small, the filtering effect is poor, and the clarity and alkali metal and alkaline earth metal do not meet the standards; in Comparative Example 4, under the same flocculation time, the flocculation effect of using only polyacrylamide is poor, and the flocculation time is short, so that most of the smaller particles cannot be removed, resulting in clarity and alkali metal and alkaline earth metal not meeting the standards. If the flocculation time is extended, the smaller particles will flocculate, but there will still be weak fluorescence, the effect is not good, and the production efficiency will be greatly reduced; in Comparative Example 5, the amount of polyacrylamide in the composite flocculant is small, the flocculation effect does not meet the requirements, and the clarity and alkali metal and alkaline earth metal do not meet the standards.

[0099] In summary, it is shown that the preparation method of the present invention can improve the quality uniformity and content of medicinal aluminum chloride hexahydrate, and is easy to realize industrial production.

[0100] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit and essential features of the present invention. Therefore, the embodiments should be considered exemplary and non-restrictive in all respects, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims be included in the present invention.

[0101] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality, characterized in that: The preparation method of medicinal aluminum chloride hexahydrate comprises the following steps: dissolving industrial-grade aluminum chloride hexahydrate in deionized water, adjusting the pH value to 1-2, adding a composite flocculant for stirring and flocculation, and then filtering, concentrating and crystallizing in stages, and centrifuging to obtain the medicinal aluminum chloride hexahydrate.

2. The method for preparing a pharmaceutical aluminum chloride hexahydrate with uniform quality according to claim 1, characterized in that: The preparation method of the medicinal aluminum chloride hexahydrate comprises the following specific steps: Step 1, dissolving and flocculating: adding industrial grade aluminum chloride hexahydrate into deionized water, heating to 70-80°C to dissolve, adjusting the pH of the solution to 1-2 with hydrochloric acid, adding a composite flocculant made of a mixture of polyaluminum chloride and polyacrylamide into the solution, stirring for 20-30 minutes, and letting it stand to form an aluminum chloride aqueous solution with floccules; Step 2, filtration: filtering the aluminum chloride aqueous solution with flocs through a two-stage filter element to remove the flocs, thereby obtaining an aluminum chloride aqueous solution; Step 3, concentration: the aluminum chloride aqueous solution is concentrated in two stages: in the first stage, the solution is concentrated under reduced pressure quickly until crystallization occurs, and in the second stage, the concentration is slowed down to allow crystal growth. When the amount of evaporated water is 60-70% of the amount of deionized water used in step (1), the concentration is stopped to obtain an aluminum chloride hexahydrate mixed solution; Step 4, cooling: continue to stir the aluminum chloride hexahydrate mixture and cool it to below 38° C. with cooling water; Step 5, centrifugation: centrifuge the cooled aluminum chloride hexahydrate mixture for the first time, 20 to 40 minutes per centrifuge, to obtain pharmaceutical aluminum chloride hexahydrate.

3. The method for preparing a pharmaceutical aluminum chloride hexahydrate with uniform quality according to claim 1, characterized in that: The mass ratio of industrial grade aluminum chloride hexahydrate to deionized water is 1:0.6-0.

7.

4. The method for preparing a pharmaceutical aluminum chloride hexahydrate with uniform quality according to claim 1, characterized in that: The added amount of the composite flocculant is 0.1-0.2% of the mass of aluminum chloride hexahydrate; in the composite flocculant, the mass ratio of polyaluminum chloride to polyacrylamide is 1:0.8-1:1.

2.

5. The method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality according to claim 1, characterized in that: The pressure of reduced pressure concentration is -0.095 to -0.1 MPa.

6. A method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality according to claim 1 or 5, characterized in that: The conditions for rapid decompression concentration in the first stage are: pressure of -0.095 to -0.1 MPa, temperature of 65 to 70°C, and stirring speed of 15 to 20 r / min.

7. A method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality according to claim 1 or 5, characterized in that: The conditions for the second stage of slow decompression concentration are: pressure of -0.095 to -0.1 MPa, temperature of 55 to 65°C, and stirring speed of 10 to 15 r / min.

8. The method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality according to claim 1, characterized in that: The centrifugation further comprises, after the first centrifugation, uniformly spraying 10-12% hydrochloric acid on the surface of the solid material after the first centrifugation, and then performing a second centrifugation, 30-40 minutes / machine.

9. The method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality according to claim 1, characterized in that: The amount of 10-12% hydrochloric acid used is 2-3% of the mass of the solid material after the first centrifugation.

10. The method for preparing pharmaceutical aluminum chloride hexahydrate with uniform quality according to claim 1, characterized in that: The filtering element adopts a two-stage filter element of 1μm filter element + 0.22μm filter element.

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