Method for producing medicinal calcium carbonate with low content of chlorine, barium, magnesium and iron ions

Abstract

The invention belongs to the technical field of medicinal preparations, and particularly relates to a method for producing medicinal calcium carbonate with low content of chlorine, barium, magnesium and iron ions, which comprises the following steps: adding purified water into a general zone reaction kettle 1, adding calcium oxide while stirring, and reacting to obtain calcium hydroxide; dropwise adding concentrated hydrochloric acid into a system of the reaction kettle 1 under the condition of controlling the temperature, and after dropwise adding, carrying out heat preservation reaction until the end to obtain a calcium chloride solution; adding purified water into a general area reaction kettle 2, then adding ammonium carbonate, and stirring until the solution is clear to obtain an ammonium carbonate solution; filtering the ammonium carbonate solution in the reaction kettle 2 through a millipore filter membrane to enter a reaction kettle 3 in a clean area, filtering the calcium chloride solution in the reaction kettle 1 through the millipore filter membrane, dropwise adding the calcium chloride solution into the reaction kettle 3, and centrifuging to obtain a calcium carbonate wet product after the heat preservation reaction is finished; adding purified water into the calcium carbonate wet product, pulping, centrifuging and drying to obtain the medicinal calcium carbonate. On the basis of a double decomposition method, the method has the advantages of simplicity in operation, low cost, capability of realizing mass production and the like.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pharmaceutical preparations, and particularly relates to a method for producing medicinal calcium carbonate with low contents of chlorine ions, barium ions, magnesium ions and iron ions. BACKGROUND

[0002] Calcium carbonate is a common inorganic compound and a commonly used medicinal component. The preparation, calcium carbonate injection, has the effect of calcium supplement and is mainly used for preventing and treating osteoporosis caused by calcium deficiency.

[0003] When calcium carbonate is used as a raw material, in order to reduce the harm of various metal and non-metal ions to the human body, the contents of various metal and non-metal ions need to be controlled to meet the relevant quality standards and be as low as possible. In the calcium carbonate raw material, the non-metal ion that needs to be controlled is mainly chlorine ion. Chlorine ion is an important component for maintaining the acid-base balance and blood osmotic pressure of the human body. When the content of chlorine ion is too high, the human body may suffer from acid-base imbalance, electrolyte disorder, impaired nerve and muscle function, and aggravated kidney burden. The metal ions that need to be controlled in the calcium carbonate raw material are mainly barium ions, magnesium ions and iron ions, which are all essential trace elements for the human body. However, if too much is ingested and cannot be metabolized and excreted in the body, it will accumulate in the body and cause harm to the human body. Common barium, magnesium and iron ion enrichment may cause serious damage to the gastrointestinal tract, liver, cardiovascular system and immune function.

[0004] At present, the chemical synthesis methods of calcium carbonate mainly include double decomposition preparation method and carbonization method.

[0005] The carbonization method is generally used for the preparation of industrial calcium carbonate. In order to meet the corresponding quality requirements, a complex preparation process is needed when it is used for the preparation of medicinal calcium carbonate. The process has many steps, is complicated to operate, has high control requirements, and is not conducive to commercial production. For example, Chinese patent CN106365190B discloses a preparation method of medicinal calcium carbonate, which comprises digestion, first aging, first carbonization, second aging, second carbonization and the like. In the process, the pH needs to be precisely controlled, and sucrose and phosphoric acid need to be continuously introduced. Finally, calcium carbonate meeting the quality requirements can be obtained. Overall, the carbonization method has many reaction steps, is complicated to operate, has high control requirements, and has high difficulty in transferring between general and clean areas, which is not conducive to large-scale commercial production.

[0006] The double decomposition method generally refers to the reaction of water-soluble calcium salt and water-soluble carbonate under certain conditions to obtain calcium carbonate solid. This method can produce products with relatively high purity. However, due to the fast and difficult-to-control reaction speed, a large amount of chlorine ions and other metal ions such as magnesium and iron will be attached to the obtained product, which needs to be removed by a large number of water washing.

[0007] The information disclosed in this Background section is only for the purpose of increasing an understanding of the general context of the present application and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art that is already known in this field. SUMMARY

[0008] The present application is to solve the above problems, the present application based on the double decomposition method, a method for producing low-chlorine, barium, magnesium, iron ion content of medicinal calcium carbonate.

[0009] The present application provides a method for producing low-chlorine, barium, magnesium, iron ion content of medicinal calcium carbonate, the reaction formula realized by the technical scheme is as follows:

[0010]

[0011] Specifically includes the following steps:

[0012] Step S1, adding a batch of purified water to the general area reaction kettle 1, and adding a batch of calcium oxide under stirring, and reacting to obtain calcium hydroxide;

[0013] Step S2, under the control of temperature conditions, a batch of concentrated hydrochloric acid is added dropwise to the system of the general area reaction kettle 1, and after the dropwise addition is completed, the reaction is kept for a certain time to obtain a calcium chloride solution;

[0014] Step S3, adding a batch of purified water to the general area reaction kettle 2, and then adding a batch of ammonium carbonate, and stirring until the solution is clear to obtain an ammonium carbonate solution;

[0015] Step S4, the ammonium carbonate solution in the general area reaction kettle 2 is filtered into the clean area reaction kettle 3 through a microporous filter membrane, and then the calcium chloride solution in the general area reaction kettle 1 is also filtered and added dropwise into the clean area reaction kettle 3, and after the reaction is kept for a certain time, centrifugation is carried out to obtain calcium carbonate wet product;

[0016] Step S5, adding a batch of purified water to the calcium carbonate wet product to make pulp, and then centrifuging and drying to obtain calcium carbonate product, i.e., medicinal calcium carbonate.

[0017] In the present application, in step S1, the mass ratio of calcium oxide to purified water is 1:1 to 1:5; preferably, the mass ratio of calcium oxide to purified water is 1:2 to 1:3.

[0018] In the present application, in step S2, the molar ratio of concentrated hydrochloric acid to calcium oxide is 1:1-1:4, the temperature needs to be controlled between 25-95°C when adding concentrated hydrochloric acid, the reaction temperature needs to be controlled between 25-95°C when keeping the reaction, and the keeping reaction time is 1-12h. Preferably, in step S2, the molar ratio of concentrated hydrochloric acid to calcium oxide is 1:1.8-1:2.2, the temperature needs to be controlled between 40-50°C when adding concentrated hydrochloric acid, the reaction temperature needs to be controlled between 40-50°C when keeping the reaction, and the keeping reaction time is 2-4h.

[0019] In the present application, in step S3, the ratio of ammonium carbonate to purified water is 1:6-1:12, and the molar ratio of ammonium carbonate to calcium oxide is 1:1-1:1.2.

[0020] In the present application, in step S4, the calcium chloride solution is added to the ammonium carbonate solution, the temperature in the reaction kettle 3 is controlled to be 20-95°C when adding, the total adding time is controlled to be 0.5-10h, the reaction temperature is controlled to be 20-95°C after adding, and the keeping reaction time is 0.5-12h. Preferably, in step S4, the ammonium carbonate solution and the calcium chloride solution are both filtered into the reaction kettle 3 through a 0.22μm microporous filter membrane.

[0021] In the present application, in step 5, the mass ratio of the purified water to the calcium carbonate wet product for beating is 1:4-1:5, and the beating temperature is 20-90°C. Preferably, in step 5, the beating temperature is 60-70°C, and the drying is performed in a vacuum drying oven at 70-80°C for 12-24h.

[0022] Effects and advantages of the present application

[0023] The present application provides a production process of medicinal calcium carbonate with low chloride ion, barium ion, magnesium ion and iron ion content, based on the double decomposition method, which is simple to operate, low in cost and can be mass-produced. Compared with the prior art, the present application has at least the following advantages:

[0024] (1) fewer steps, and mass commercial production;

[0025] (2) simple operation, and smooth transfer from a general area to a clean area;

[0026] (3) the chloride ion, barium ion, magnesium ion and iron ion content in the produced calcium carbonate product is far lower than that of the products obtained by other technologies. DETAILED DESCRIPTION

[0027] In order to make the technical means, creative features, purposes and effects of the present application easy to understand, the following will make a specific description of the method for producing medicinal calcium carbonate with low chloride ion, barium ion, magnesium ion and iron ion content.

[0028] The raw materials and reagents used in the examples and comparative examples of the present application are all commercially available unless otherwise specified. The test methods not mentioned are national standards.

[0029] Calcium oxide, industrial grade; concentrated hydrochloric acid, industrial grade.

[0030] <Example 1>

[0031] Into a 2000L reactor 1 in the general area, 420kg of purified water was added, and stirring and cooling water were started. Then 210kg of calcium oxide was slowly added while the temperature was controlled at 20-60°C. After the temperature was stabilized at 40°C, 562L of concentrated hydrochloric acid was slowly added dropwise while the temperature was controlled at 25-95°C. After the addition was completed, the temperature was maintained at 40-50°C for 1h to obtain a calcium chloride solution.

[0032] Into a 3000L reactor 2 in the general area, 2160kg of purified water was added, and 360kg of ammonium carbonate was added. After stirring until the solution was clear, an ammonium carbonate solution was obtained.

[0033] The ammonium carbonate solution in the reactor 2 in the general area was filtered through a 0.22μm filter membrane into a 5000L reactor 3 in the clean area. The calcium chloride solution in the reactor 1 in the general area was filtered through a 0.22μm filter membrane, and then slowly added dropwise into the ammonium carbonate solution in the 5000L reactor 3 while the temperature of the solution in the 5000L reactor 3 was controlled at 20-95°C. The filtering and dropping time was controlled at about 0.5h. After the addition was completed, the reaction temperature was controlled at 20-95°C for 0.5h, and then the product was filtered to obtain a calcium carbonate wet product.

[0034] The calcium carbonate wet product was transferred into the 5000L reactor 3 again, and 840kg of purified water was added. The temperature was controlled at 60-70°C, and the slurry was stirred for about 1h. Then the product was filtered and dried in a vacuum drying oven at 60-70°C under reduced pressure for 12h to obtain a calcium carbonate product.

[0035] <Example 2>

[0036] Into a 2000L reactor 1 in the general area, 630kg of purified water was added, and stirring and cooling water were started. Then 210kg of calcium oxide was slowly added while the temperature was controlled at 20-60°C. After the temperature was stabilized at 40-50°C, 686L of 36% concentrated hydrochloric acid was slowly added dropwise while the temperature was controlled at 25-95°C. After the addition was completed, the temperature was maintained at 40-50°C for 12h to obtain a calcium chloride solution.

[0037] Into a 5000L reactor 2 in the general area, 4320kg of purified water was added, and 432kg of ammonium carbonate was added. After stirring until the solution was clear, an ammonium carbonate solution was obtained.

[0038] The ammonium carbonate solution in the general zone reactor 2 was filtered through a 0.22 μm microporous filter into the clean zone 10000 L reactor 3, the temperature in the reactor 3 was controlled at 20-95℃, the calcium chloride solution in the general zone reactor 1 was slowly filtered and added into the clean zone reactor 3 through a 0.22 μm microporous filter, the filtering and adding time was controlled at about 10 h, after the adding was completed, the reaction temperature was controlled at 20-95℃ for 12 h, and then the calcium carbonate wet product was obtained by centrifugation.

[0039] The calcium carbonate wet product was again transferred into the reactor 3, 1050 kg of purified water was added, the temperature was increased to 60-70℃, and the slurry was prepared for about 1 h, then the slurry was centrifuged and placed in a vacuum drying oven at 70-80℃ for 24 h under reduced pressure to obtain the calcium carbonate product.

[0040] <Comparative Example 1>

[0041] 420 g of purified water was added to a 1000 ml reaction bottle 1, the stirring and cooling water were turned on, 210 g of calcium oxide was slowly added, the temperature was controlled at 20-80℃ during the adding process, after the temperature was stabilized at 40-50℃, 710 g of concentrated hydrochloric acid was slowly added dropwise, the temperature was controlled at 20-80℃ during the adding process, after the adding was completed, the temperature was maintained at 40-50℃ for 2 h to obtain a calcium chloride solution.

[0042] Ammonia was added to the above calcium chloride solution to adjust the pH, and the high-pressure kettle was transferred, the stirring speed was adjusted to 1500 rpm / min, the temperature was controlled at 40-50℃, 20% carbon dioxide gas was introduced into the high-pressure kettle, the gas flow rate was controlled at 1.2 L / min by a gas flow meter, and carbonization was carried out for 3 h; after the carbonization was completed, the gas flow rate was controlled at 2.4 L / min for 30 min of over-carbonization, and the calcium carbonate wet product was obtained by filtration.

[0043] The calcium carbonate wet product was transferred into a reaction bottle, 1200 g of purified water was added, the temperature was increased to 60-70℃, the slurry was prepared for 1 h, then the slurry was filtered, placed in a vacuum drying oven at 70-80℃ for 24 h under reduced pressure, and the calcium carbonate product was obtained.

[0044] <Test Example>

[0045] The test results of the calcium carbonate products obtained in each example and comparative example are compared as shown in Table 1 below.

[0046] The corresponding standards and instrument manufacturers and model information used for testing are as follows:

[0047] Inductively coupled plasma mass spectrometer (ICP-MS) was purchased from Thermo Fisher Scientific, model ICAP-RQ.

[0048] Ion chromatograph was purchased from Thermo Fisher Scientific, model Dionex Aquion.

[0049] Table 1. Test results of calcium carbonate products

[0050]

[0051]

[0052] From the comparison of the data in Table 1, it can be seen that the detection data of each detection item in the calcium carbonate product obtained in the embodiment according to the technical solution is significantly lower than that of the comparative example, which shows that the technical solution disclosed in the present application can obtain a pharmaceutical calcium carbonate product with low content of chlorine ions, barium ions, magnesium ions and iron ions.

[0053] The above embodiments are preferred cases of the present application and are not intended to limit the protection scope of the present application.

Claims

1. A process for producing pharmaceutical grade calcium carbonate having low levels of chloride, barium, magnesium, and iron ions, characterized in that, It comprises the following steps: Step S1, adding a dosing amount of purified water into the general area reaction kettle 1, adding a dosing amount of calcium oxide under stirring, and reacting to obtain calcium hydroxide; Step S2, under temperature control, adding a dosing amount of concentrated hydrochloric acid into the system of the general area reaction kettle 1, keeping warm after the addition is completed, and reacting to the end to obtain a calcium chloride solution; Step S3, adding a dosing amount of purified water into the general area reaction kettle 2, then adding a dosing amount of ammonium carbonate, and stirring to dissolve clear to obtain an ammonium carbonate solution; Step S4, filtering the ammonium carbonate solution in the general area reaction kettle 2 into the clean area reaction kettle 3 through a microporous filter membrane, then filtering and adding the calcium chloride solution in the general area reaction kettle 1 into the clean area reaction kettle 3, and centrifuging to obtain calcium carbonate wet products after keeping warm to the end of the reaction; Step S5, adding a dosing amount of purified water into the calcium carbonate wet products to make pulp, and centrifuging and drying to obtain finished calcium carbonate, i.e. medicinal calcium carbonate.

2. The method according to claim 1, wherein: wherein In step S1, the mass ratio of the calcium oxide to the purified water is 1:1-1:

5.

3. The method according to claim 2, wherein: wherein In step S1, the mass ratio of the calcium oxide to the purified water is 1:2-1:

3.

4. The method according to claim 1, wherein: wherein, In step S2, the molar ratio of the concentrated hydrochloric acid to the calcium oxide is 1:1-1:4, the temperature is controlled between 25-95℃ when the concentrated hydrochloric acid is added, the reaction temperature is controlled between 25-95℃ during keeping warm, and the keeping warm time is 1-12h.

5. The method according to claim 4, wherein: wherein In step S2, the molar ratio of the concentrated hydrochloric acid to the calcium oxide is 1:1.8-1:2.2, the temperature is controlled between 40-50℃ when the concentrated hydrochloric acid is added, the reaction temperature is controlled between 40-50℃ during keeping warm, and the keeping warm time is 2-4h.

6. The method according to claim 1, wherein: wherein In step S3, the ratio of the ammonium carbonate to the purified water is 1:6-1:12, and the molar ratio of the ammonium carbonate to the calcium oxide is 1:1-1:1.

2.

7. The method according to claim 1, wherein: wherein In step S4, the calcium chloride solution is added into the ammonium carbonate solution, the temperature in the reaction kettle 3 is controlled between 20-95℃ when the calcium chloride solution is added, the total adding time is controlled between 0.5-10h, the keeping warm temperature is 20-95℃ after the addition is completed, and the keeping warm time is 0.5-12h.

8. The method according to claim 7, wherein: wherein In step S4, the ammonium carbonate solution and the calcium chloride solution are filtered through a 0.22 μm microporous filter into the reactor 3.

9. The method for producing pharmaceutical grade calcium carbonate with low content of chlorine, barium, magnesium and iron ions according to claim 1, characterized in that: wherein, In step 5, the mass ratio of the purified water to the wet calcium carbonate is 1:4-1:5, and the beating temperature is 20-90°C.

10. The method for producing pharmaceutical grade calcium carbonate with low content of chlorine, barium, magnesium and iron ions according to claim 9, characterized in that: wherein In step 5, the beating temperature is 60-70°C, and the drying is performed in a vacuum drying oven at 70-80°C for 12-24 hours.

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