阅读说明：本技术 多种维生素铁胶囊及其制备方法 (Multivitamin iron capsule and preparation method thereof ) 是由 邓文峰 刘海琼 符晓霞 于 2021-06-30 设计创作，主要内容包括：本发明提供一种多种维生素铁胶囊及其制备方法,属于药物制备技术领域,所述制备方法包括以下步骤：S1：取49.19重量份富马酸亚铁、146.28重量份乳糖,混匀得混合物X；S2：取部分混合物X与0.5重量份叶酸及0.23重量份维生素B12粉,混匀得混合物Y；S3：取剩余的混合物X与200.6重量份维生素C、3.2重量份硬脂酸镁及混合物Y,混匀得待装囊物料；S4：取待装囊物料经装囊,即得所述多种维生素铁胶囊。由此,得到了稳定性好、溶出度高的多种维生素铁胶囊,更有利于人体吸收利用。(The invention provides a multivitamin iron capsule and a preparation method thereof, belonging to the technical field of medicine preparation, wherein the preparation method comprises the following steps: s1: mixing 49.19 parts by weight of ferrous fumarate and 146.28 parts by weight of lactose uniformly to obtain a mixture X; s2: mixing part of the mixture X with 0.5 part by weight of folic acid and 0.23 part by weight of vitamin B12 powder, and mixing uniformly to obtain a mixture Y; s3: mixing the rest mixture X with 200.6 parts by weight of vitamin C, 3.2 parts by weight of magnesium stearate and the mixture Y uniformly to obtain a material to be encapsulated; s4: and (3) encapsulating the material to be encapsulated to obtain the multivitamin iron capsule. Therefore, the multivitamin iron capsule with good stability and high dissolution rate is obtained, and is more beneficial to absorption and utilization of a human body.)

1. The multivitamin iron capsule is characterized in that the raw materials for preparing the effective components of the multivitamin iron capsule comprise the following components in parts by weight: 49.19 parts of ferrous fumarate, 146.28 parts of lactose, 0.5 part of folic acid, 0.23 part of vitamin B12 powder, 200.6 parts of vitamin C and 3.2 parts of magnesium stearate.

2. The multivitamin iron capsule according to claim 1, wherein the folic acid is prepared by a method comprising the steps of:

1) under the protection of inactive gas, 1,1,3, 3-tetramethoxy-2-propanol is mixed with acidic aqueous solution, N-p-aminobenzoyl-L-glutamic acid is added for reaction, the obtained diimine solid is reacted with triaminopyrimidine sulfate, and then the pH value is adjusted to be acidic, so that a crude folic acid product is obtained, wherein the specific chemical reaction formula is as follows:

2) adding the folic acid crude product into a concentrated hydrochloric acid-acetone solution, heating to 53-56 ℃ for dissolving for the first time, filtering to remove insoluble substances while the solution is hot, adding water into filtrate, slowly cooling to perform primary crystallization, dispersing the obtained folic acid crystals in water, adding an alkaline aqueous solution until the pH value is 9.0-10.5, heating for dissolving for the second time, adsorbing, filtering, adjusting the pH value to 3.0-3.5, cooling to perform secondary crystallization, filtering, and drying to obtain the folic acid.

3. The multivitamin iron capsule of claim 2, wherein in step 2), the concentrated hydrochloric acid-acetone solution is prepared by mixing the concentrated hydrochloric acid-acetone solution in a volume ratio of 1: 4-6 of concentrated hydrochloric acid and acetone.

4. The multivitamin iron capsule according to claim 2 or 3, wherein in step 2), the weight-to-volume ratio of the crude folic acid to the concentrated hydrochloric acid-acetone solution is 1 g: 20-25 mL.

5. The multivitamin iron capsule according to claim 2 or 3, wherein in step 2), the temperature of the first crystallization is 25-30 ℃;

the temperature of the second heating is 80-90 ℃;

the temperature of the second crystallization is 30-50 ℃.

6. The multivitamin iron capsule according to claim 2 or 3, wherein in step 2), the adsorbent for adsorption is activated carbon or diatomaceous earth.

7. The multivitamin iron capsule according to any one of claims 1 to 3, wherein the lactose is refined by adding lactose raw material into water, heating to dissolve, decoloring the obtained lactose solution, filtering with an ultrafiltration membrane, adding ethanol, slowly cooling to crystallize, centrifuging to collect crystals, and drying to obtain the lactose.

8. The multivitamin iron capsule of claim 7,

in the refining method, the volume ratio of the water to the ethanol is 1: 2-3;

the weight volume ratio of the lactose to the water is 1 kg: 2.3-3L.

9. The multivitamin iron capsule of claim 7,

in the refining method, the heating and dissolving temperature is 55-60 ℃;

the temperature of the crystallization is below 35 ℃.

10. The method of preparing a multivitamin iron capsule of any one of claims 1 to 9, comprising the steps of:

s1: taking ferrous fumarate and lactose, and uniformly mixing to obtain a mixture X;

s2: mixing part of the mixture X with folic acid and vitamin B12 powder to obtain mixture Y;

s3: mixing the rest mixture X with vitamin C, magnesium stearate and mixture Y to obtain material to be encapsulated;

s4: and (3) encapsulating the material to be encapsulated to obtain the multivitamin iron capsule.

Technical Field

The invention relates to preparation of capsules, in particular to a multivitamin iron capsule and a preparation method thereof.

Background

Vitamins are a class of trace organic substances that maintain the normal physiological functions of humans and animals, and are generally available in the diet, and in particular, they play an important role in the growth, metabolism, and development of the human body. Iron is an essential component of human cells, has a hematopoietic function, is involved in the production of hemoglobin and the synthesis of cytochrome and various enzymes, and promotes growth. Iron also plays a role in transporting and carrying nutrients in the blood, and if iron deficiency occurs, iron deficiency anemia is caused, and in severe cases, immune function is reduced and metabolism is disturbed. Therefore, vitamins and iron are essential nutrients for human body, and the multivitamin iron capsule is a main medicament for people to rapidly supplement vitamins and iron. However, the existing technology for preparing the multi-vitamin iron capsules is relatively simple, and impurities in raw materials used for preparing the multi-vitamin iron capsules can influence the quality of products and further influence the bioavailability of the products.

Folic acid, also known as vitamin M, is a pteroic acid monoglutamic acid, one of vitamin B complexes, and the deficiency of folic acid affects the absorption of iron and, in turn, the hematopoietic function of bone marrow, causing nutritional anemia. However, in the process of preparing folic acid, the method for synthesizing folic acid by using 1,1,3, 3-tetramethoxy-2-propanol and N-p-aminobenzoyl-L-glutamic acid as main raw materials has the advantages of simple and easy synthetic steps, high yield and the like, but the purification operation is complex, and a silica gel column is required to be used for separation operation, so that the application of folic acid to industrial production is limited.

Lactose is a specific saccharide in milk of mammals, is used as a main pharmaceutic adjuvant, and the crystal property of lactose has obvious influence on the solubility, hygroscopicity, stability, mouthfeel and the like of compatible materials, so that the uniformly distributed microcrystalline lactose becomes a new direction in the lactose research process. At present, the lactose microcrystallization in the industry mainly adopts mechanical grinding and spray drying, the microcrystalline lactose crystal prepared by the mechanical grinding has large shape difference, uneven crystal face energy and wide product particle size distribution; the lactose crystal with uniform particle size can be obtained by the spray drying method, but the content of amorphous lactose in the product is higher, which seriously influences the subsequent application thereof.

Disclosure of Invention

Aiming at the problems, the invention provides a multivitamin iron capsule and a preparation method thereof.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

the multivitamin iron capsule comprises the following raw materials for preparing effective components in parts by weight: : 49.19 parts of ferrous fumarate, 146.28 parts of lactose, 0.5 part of folic acid, 0.23 part of vitamin B12 powder, 200.6 parts of vitamin C and 3.2 parts of magnesium stearate.

Further, the preparation method of folic acid comprises the following steps:

1) under the protection of inactive gas, 1,1,3, 3-tetramethoxy-2-propanol is mixed with acidic aqueous solution, N-p-aminobenzoyl-L-glutamic acid is added for reaction, the obtained diimine solid is reacted with triaminopyrimidine sulfate, and then the pH value is adjusted to be acidic, so that a crude folic acid product is obtained, wherein the specific chemical reaction formula is as follows:

2) adding the folic acid crude product into a concentrated hydrochloric acid-acetone solution, heating to 53-56 ℃ for dissolving for the first time, filtering to remove insoluble substances (the insoluble substances are mainly a byproduct N-p-aminobenzoyl-L-glutamic acid, the content of which exceeds 2/5 of the total weight of the folic acid crude product) while the solution is hot, adding water into the filtrate, slowly cooling to perform primary crystallization, dispersing the obtained folic acid crystals in water, adding an alkaline aqueous solution until the pH value is 9.0-10.5, heating for dissolving for the second time, adsorbing, filtering, adjusting the pH value to 3.0-3.5, cooling to perform secondary crystallization, filtering and drying to obtain the folic acid.

Further, in the step 2), the concentrated hydrochloric acid-acetone solution is prepared by mixing the following raw materials in a volume ratio of 1: 4-6 of concentrated hydrochloric acid and acetone.

Further, in the step 2), the weight-volume ratio of the folic acid crude product to the concentrated hydrochloric acid-acetone solution is 1 g: 20-25 mL.

Further, in the step 2), the temperature of the first crystallization is 25-30 ℃;

the temperature of the second heating is 80-90 ℃;

the temperature of the second crystallization is 30-50 ℃.

Further, in the step 2), the adsorbent for adsorption is activated carbon or diatomite.

Further, the refining method of the lactose comprises the steps of adding lactose raw materials into water, heating and dissolving, decoloring the obtained lactose solution, filtering the obtained lactose solution by using an ultrafiltration membrane, adding ethanol, slowly cooling and crystallizing, centrifuging, collecting crystals, and drying to obtain the lactose.

Further, in the refining method, the volume ratio of the water to the ethanol is 1: 2-3;

the weight volume ratio of the lactose to the water is 1 kg: 2.3-3L.

Further, in the refining method, the heating and dissolving temperature is 55-60 ℃;

the temperature of the crystallization is below 35 ℃.

A preparation method of a multivitamin iron capsule comprises the following steps:

s1: taking ferrous fumarate and lactose, and uniformly mixing to obtain a mixture X;

s2: mixing part of the mixture X with folic acid and vitamin B12 powder to obtain mixture Y;

s3: mixing the rest mixture X with vitamin C, magnesium stearate and mixture Y to obtain material to be encapsulated;

s4: and (3) encapsulating the material to be encapsulated to obtain the multivitamin iron capsule.

The multivitamin iron capsule and the preparation method thereof have the beneficial effects that:

the multi-vitamin iron capsule with high dissolution rate and good stability is prepared through reasonable compatibility, and is more beneficial to absorption and utilization by a human body;

according to the invention, through searching for a specific solvent, the folic acid can be completely dissolved in a concentrated hydrochloric acid-acetone solution at the temperature of 53-56 ℃, and the N-p-aminobenzoyl-L-glutamic acid is almost insoluble in the solvent of the system, and by utilizing the discovery, the folic acid and the N-p-aminobenzoyl-L-glutamic acid which are similar in physical and chemical properties can be separated through simple filtration, and silica gel column separation is not needed, so that the industrial production of the method for synthesizing the folic acid by taking 1,1,3, 3-tetramethoxy-2-propanol and the N-p-aminobenzoyl-L-glutamic acid as raw materials is facilitated;

according to the invention, the lactose is recrystallized by water and ethanol in a specific ratio to prepare the microcrystalline lactose with uniform particle size distribution, which is beneficial to improving the stability and dissolution of the multivitamin iron capsule and promoting the absorption of vitamins and iron.

Detailed Description

The technical solutions in the embodiments of the present invention are clearly and completely described below. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.

EXAMPLE 1A method for producing folic acid

The embodiment is a preparation method of folic acid, and the specific preparation process comprises the following steps in sequence:

1) under the protection of nitrogen, 3.6g (20mmol) of 1,1,3, 3-tetramethoxy-2-propanol is added into 40mL of hydrochloric acid aqueous solution with the concentration of 1moL/L, stirred for 5min at room temperature, then 10.65g (40mmol) of N-p-aminobenzoyl-L-glutamic acid is added, stirred and reacted for 1h at 50 ℃, 200mL of water is added after the reaction is finished, the mixture is placed at room temperature for 24h for crystallization, filtered, washed with water and dried in vacuum to obtain 10.0g of diimine solid with the yield of 85.54%.

Under the protection of nitrogen, 10g of diimine solid and 4.15g of sodium sulfide are added into 35mL of water, 2mol/L of sodium carbonate aqueous solution is added while stirring until the pH value of the system is 6, then 3.92g of triaminopyrimidine sulfate is added, stirring reaction is carried out at room temperature, 2mol/L of sodium carbonate aqueous solution is added while keeping the pH value of the system always 6, after 4 hours of reaction, water is added for dilution to 400mL, 0.5g of activated carbon is added, stirring is carried out for 30min for adsorption, filtering is carried out, 10 wt% of hydrochloric acid is slowly added while stirring to the filtrate until the pH value is 3.0, crystallization and filtering are carried out at room temperature, 10.5g of folic acid crude product (containing a large amount of byproduct N-p-aminobenzoyl-L-glutamic acid) is obtained, and the specific chemical reaction formula is as follows:

2) taking 35mL of concentrated hydrochloric acid with the concentration of 36 wt% and 192.5mL of acetone, and uniformly stirring and mixing to obtain a concentrated hydrochloric acid-acetone solution (the volume ratio of the concentrated hydrochloric acid to the acetone is 1:5.5) for later use;

adding 10g of folic acid crude product into 227.5mL of concentrated hydrochloric acid-acetone solution, heating to 55 ℃ for the first time while stirring, maintaining the temperature of 55 ℃ and stirring for 1h to fully dissolve folic acid, filtering to remove insoluble substances (the insoluble substances are mainly N-p-aminobenzoyl-L-glutamic acid) while hot, adding water into the obtained filtrate until partial folic acid crystals appear, slowly cooling to 30 ℃ for the first crystallization for 4h, filtering, washing with a small amount of water to obtain folic acid crystals;

dispersing folic acid crystals in water, dropwise adding 10 wt% of ammonia water to adjust the pH value to 9.5, heating to 85 ℃ while stirring, keeping the temperature at 85 ℃ and stirring until the folic acid is completely dissolved (10 wt% of ammonia water needs to be continuously supplemented to 9.5 when the pH value is reduced in the dissolving process), keeping the temperature at 85 ℃, adding 0.5g of activated carbon, stirring and adsorbing for 30min, filtering while the solution is hot, dropwise adding 10 wt% of hydrochloric acid into the filtrate to adjust the pH value to 3.0, cooling to 40 ℃ and carrying out secondary crystallization for 4h, filtering, and carrying out vacuum drying at 80 ℃ to obtain 5.70g of folic acid (marked as YS1), wherein the total yield is 67.49%, the purity is 99.61%, the content of N-p-aminobenzoyl-L-glutamic acid is 0.08%, and the content of pteroic acid is 0.05% (detected by high performance liquid chromatography according to 2015 version two parts-194 of Chinese pharmacopoeia).

Example 2-5 preparation of Folic acid

Examples 2 to 5 are respectively a method for preparing folic acid, the steps of which are basically the same as those of example 1, and the differences are only in process parameters, which are specifically shown in table 1:

TABLE 1 summary of the process parameters of examples 2 to 5

The contents of the other portions of examples 2 to 5 are the same as those of example 1.

EXAMPLE 6A method for refining lactose

Adding 1kg of lactose raw material into 2.5L of water, stirring and heating to 56 ℃ for full dissolution, maintaining the obtained lactose solution at 50 ℃, adding 10g of activated carbon, stirring and decoloring for 30min, filtering while hot, adopting an ultrafiltration membrane for filtering, then adding 5L of ethanol, slowly cooling to 30 ℃, crystallizing for 4h, centrifugally collecting crystals, and carrying out vacuum drying at 50 ℃ for 8h to obtain 0.827kg of lactose, wherein the label is RT 6.

Examples 7 to 10 lactose refining method

Examples 7 to 10 are respectively a method for refining lactose, which has substantially the same steps as in example 6, but differs only in the process parameters, as detailed in table 2:

TABLE 2 summary of the process parameters of examples 7 to 10

The contents of the other portions of examples 7 to 10 are the same as those of example 6.

EXAMPLE 11A method of preparing multivitamin iron capsules

The embodiment is a preparation method of a multivitamin iron capsule, and the specific preparation process comprises the following steps of:

s1: 49.19g of ferrous fumarate and 146.28g of lactose RT6 prepared in example 6 were weighed into a hopper mixer and mixed for 5 minutes, and after mixing, the mixture was discharged to give 195.6g of a mixture X1.

S2: weighing 0.5g of folic acid YS1 prepared in example 1 and 0.23g of vitamin B12 powder, and uniformly mixing with 2.5g of mixture X1 to obtain a mixture Y11;

uniformly mixing 10g of the mixture X1 with the mixture Y11 to obtain a mixture Y12;

uniformly mixing 30g of the mixture X1 with the mixture Y12 to obtain a mixture Y13;

90g of the mixture X1 and the mixture Y13 are mixed evenly to obtain a mixture Y1.

S3: the remaining 63.1g of mixture X1, 200.6g of vitamin C, 3.2g of magnesium stearate and mixture Y1 were mixed in a hopper mixer for 20 minutes until completely and uniformly mixed to obtain the material to be encapsulated.

S4: and (5) taking the materials to be encapsulated and encapsulating to obtain the multi-vitamin iron capsule.

Example 12-15 preparation method of multivitamin iron capsules

Examples 12 to 15 are methods of preparing multivitamin iron capsules, respectively, which are substantially the same as example 11 except that:

example 12 starting from lactose RT7 prepared in example 7 and folic acid YS2 prepared in example 2;

example 13 starting from lactose RT8 prepared in example 8 and folic acid YS3 prepared in example 3;

example 14 starting from lactose RT9 prepared in example 9 and folic acid YS4 prepared in example 4;

example 15 starting from lactose RT10 prepared in example 10 and folic acid YS5 prepared in example 5.

Experimental example 1 determination of purity of folic acid

Comparative examples 1 to 11 are comparative tests of the folic acid preparation process of example 1, and the same batch of crude folic acid was used, except that:

in comparative example 1, 36 wt% of concentrated hydrochloric acid was used in an amount of 56.5mL, and the amount of acetone was used in an amount of 171mL (the volume ratio of concentrated hydrochloric acid to acetone was about 1:3), to obtain 4.02g of folic acid, with a total yield of 47.60%, a purity of 99.42%, a content of N-p-aminobenzoyl-L-glutamic acid of 0.37%, and a content of pteroic acid of 0.09%;

in comparative example 2, 36 wt% of concentrated hydrochloric acid was used in an amount of 28.5mL and acetone was used in an amount of 199mL (the volume ratio of concentrated hydrochloric acid to acetone was about 1:7), and 5.82g of folic acid was finally obtained, with a total yield of 68.91%, a purity of 94.57%, a content of N-p-aminobenzoyl-L-glutamic acid of 3.18%, and a content of pteroic acid of 0.78%;

in comparative example 3, 36 wt% of concentrated hydrochloric acid was used in an amount of 22.7mL, and acetone was used in an amount of 127.3mL (the volume ratio of concentrated hydrochloric acid to acetone was about 1:5.5), to give 3.88g of folic acid, with a total yield of 45.94%, a purity of 99.60%, a content of N-p-aminobenzoyl-L-glutamic acid of 0.09%, and a content of pteroic acid of 0.05%;

in comparative example 4, the amount of 36 wt% concentrated hydrochloric acid was 46mL and the amount of acetone was 254mL (the volume ratio of concentrated hydrochloric acid to acetone was about 1:5.5), and 5.93g of folic acid was finally obtained, with a total yield of 70.21%, a purity of 91.44%, a content of N-p-aminobenzoyl-L-glutamic acid of 5.25%, and a content of pteroic acid of 0.81%;

the temperature for the first dissolution in comparative example 5 was 50 ℃, and 4.49g of folic acid was finally obtained, with a total yield of 53.16%, a purity of 99.54%, a content of N-p-aminobenzoyl-L-glutamic acid of 0.10%, and a content of pteroic acid of 0.12%;

the temperature for the first dissolution in comparative example 6 was 60 ℃, and 5.86g of folic acid was finally obtained, with a total yield of 69.39%, a purity of 93.85%, a content of N-p-aminobenzoyl-L-glutamic acid of 4.92%, and a content of pteroic acid of 0.82%;

in comparative example 7, before the second heating, ammonia was added to adjust the pH to 8.5, and 5.25g of folic acid was finally obtained, with a total yield of 62.16%, a purity of 99.23%, a content of N-p-aminobenzoyl-L-glutamic acid of 0.20%, and a content of pteroic acid of 0.35%;

in comparative example 8, before the second heating, ammonia was added to adjust the pH to 11, to finally obtain 5.32g of folic acid, the total yield was 62.99%, the purity was 98.64%, the content of N-p-aminobenzoyl-L-glutamic acid was 0.24%, and the content of pteroic acid was 0.62%;

before the second crystallization in comparative example 9, hydrochloric acid was added to adjust the pH to 2.5, and 5.37g of folic acid was finally obtained, with a total yield of 63.58%, a purity of 99.16%, a N-p-aminobenzoyl-L-glutamic acid content of 0.22%, and a pteroic acid content of 0.49%;

before the second crystallization in the comparative example 10, hydrochloric acid was added to adjust the pH to 4.0, and 4.96g of folic acid was finally obtained, with a total yield of 58.73%, a purity of 99.52%, a content of N-p-aminobenzoyl-L-glutamic acid of 0.10%, and a content of pteroic acid of 0.09%;

comparative example 11 according to the Folic acid Synthesis (No. 10, No. 12 of J.New.2001), 5.68g of Folic acid (designated YS1) was obtained at a total yield of 67.25%, a purity of 99.64%, a content of N-p-aminobenzoyl-L-glutamic acid of 0.07%, and a content of pteroic acid of 0.06% by silica gel column separation.

In conclusion, the total yield, purity, N-p-aminobenzoyl-L-glutamic acid content and pteroic acid content of the folic acids prepared in examples 1 to 5 and comparative examples 1 to 11 were comprehensively evaluated, and the scope of the present invention claimed was finally determined.

Experimental example 2 Performance measurement of lactose and multivitamin iron capsules

Comparative examples 12 to 14 are comparative tests of the lactose refining process of example 6, and the same batch of lactose raw material was used, except that:

comparative example 12, where the amount of water was 3.5L and the amount of ethanol was 7.5L, resulted in 0.705kg of lactose, labeled DRT 1;

comparative example 13 water dosage was 2.5L, ethanol dosage was 3.75L, resulting in 0.689kg lactose, labeled DRT 2;

comparative example 14, where the amount of water was 2.5L and the amount of ethanol was 8.75L, resulted in 0.837kg lactose, labeled DRT 3;

this comparative test was no longer used, since at 56 ℃ water levels below 2.3L did not dissolve 1kg of lactose very well.

Comparative examples 15 to 18 are comparative tests of the multivitamin iron capsule preparation process in example 11, and all employ folic acid YS1 prepared in example 1 as a raw material, except that:

in comparative example 15, lactose DRT1 prepared in comparative example 11 was used as a starting material;

in comparative example 16, lactose DRT2 prepared in comparative example 12 was used as a starting material;

in comparative example 17, lactose DRT3 prepared in comparative example 13 was used as a starting material;

in comparative example 18, a lactose raw material (same batch as the lactose raw material used in example 6) was used as a raw material.

21) Dissolution testing

The multivitamin iron capsules prepared in examples 11 to 15 and comparative examples 15 to 18 were subjected to in vitro release (ferrous fumarate) comparison tests in a ph4.0 acetate buffer, a ph6.8 phosphate buffer and water, respectively, according to the first method of the chinese pharmacopoeia (2015 edition, four 0931), and the following specific results were obtained:

TABLE 3 dissolution data of ferrous fumarate in acetate buffer at pH4.0

Time (min)	5	10	15	20	30	45	60	90
									Example 11	37.61	54.27	65.35	75.14	85.11	96.74	99.98	99.98
Example 12	39.27	56.52	64.98	75.37	88.17	99.62	100.02	100.02
									Example 13	37.41	52.14	63.58	74.15	86.19	97.16	100.09	100.10
Example 14	38.21	53.79	64.85	74.67	85.74	96.96	100.07	100.03
									Example 15	38.19	54.11	68.14	78.25	85.57	96.28	100.01	100.02
Comparative example 15	28.10	46.72	53.14	66.10	72.94	85.75	98.77	98.77
									Comparative example 16	26.27	41.82	50.37	62.42	70.25	81.64	92.42	93.56
Comparative example 17	12.1	27.54	40.67	50.12	59.89	64.18	70.21	80.16
									Comparative example 18	10.8	25.97	39.54	48.61	59.12	65.37	70.08	79.69

TABLE 4 dissolution data of ferrous fumarate in phosphate buffer at pH6.8

Time (min)	5	10	15	20	30	45	60	90
									Example 11	53.43	72.64	83.59	93.56	99.91	100	99.98	99.98
Example 12	55.15	74.56	83.98	93.45	99.96	100.02	100.01	100.02
									Example 13	54.63	73.01	84.26	93.75	99.9	100.06	100.08	100.07
Example 14	53.68	73.56	83.26	93.98	99.89	100.06	100.07	100.03
									Example 15	54.16	73.12	85.61	94.25	99.94	100.3	100.04	100.03
Comparative example 15	38.21	57.86	72.99	89.56	94.74	98.73	98.74	98.74
									Comparative example 16	46.75	67.27	79.46	90.13	96.75	98.27	98.27	98.27
Comparative example 17	20.01	49.58	66.74	74.28	84.01	95.04	99.67	99.66
									Comparative example 18	19.21	35.76	60.57	70.21	81.69	91.45	93.56	99.42

TABLE 5 dissolution data of ferrous fumarate in water

Time (min)	5	10	15	20	30	45	60	90
									Example 11	40.23	56.27	68.14	79.59	89.98	99.68	100.02	100.02
Example 12	40.12	55.69	66.97	78.98	88.01	98.21	99.98	99.98
									Example 13	40.54	57.11	69.56	79.96	89.45	98.25	100.09	100.1
Example 14	40.37	56.98	68.99	79.53	89.46	99.21	100.04	100.03
									Example 15	40.26	57.02	67.72	78.59	89.25	98.99	100.01	100.02
Comparative example 15	31.02	47.58	58.76	68.85	79.91	89.27	98.77	98.77
									Comparative example 16	28.64	45.86	57.46	66.13	75.75	86.27	97.27	98.27
Comparative example 17	12.04	28.12	41.89	50.12	59.89	66.58	75.64	80.36
									Comparative example 18	13.14	30.25	40.27	48.36	56.97	63.75	72.56	80.11

By comprehensively analyzing the dissolution data of the ferrous fumarate in tables 3 to 5, it can be seen that the dissolution rates of the multivitamin iron capsules prepared in examples 11 to 15 are good, while the dissolution rates of the multivitamin iron capsules prepared in comparative examples 15 to 18 are obviously poor, and since the difference between the comparative examples 15 to 18 and the example 11 is only that the microcrystalline lactose is different, the microcrystalline lactose prepared by the lactose refining method disclosed by the invention is beneficial to improving the dissolution rates of the multivitamin iron capsules.

22) Stability detection

The multivitamin iron capsules prepared in examples 11 to 15 and comparative examples 15 to 18 were placed at 40. + -. 2 ℃ and RH 75. + -. 5% for 6 months, during which time the samples were taken at 1 st, 2 nd, 3 th and 6 th months, tested according to the stability test item, and compared with the data on day 0.

The method comprises the following steps of respectively detecting indexes such as vitamin C content (according to the second part-1237 of the 'Chinese pharmacopoeia' 2015 edition), ferrous fumarate content (according to the second part-1438 of the 'Chinese pharmacopoeia 2015 edition), moisture (according to the first method in the' Chinese pharmacopoeia 2015 edition three general rules-0832) and the like, and detecting specific detection results as follows:

TABLE 6 stability test results List

As can be seen from table 6, the multivitamin iron capsules prepared in examples 11 to 15 have good stability, while the multivitamin iron capsules prepared in comparative examples 15 to 18 have significantly poor stability, and the difference between the comparative examples 15 to 18 and example 11 is only that microcrystalline lactose, so that it is found that the microcrystalline lactose prepared by the lactose refining method of the present invention is advantageous for improving the stability of the multivitamin iron capsules.

It is to be understood that the described embodiments are merely a few embodiments of the invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.