WO2023082626A1 - Method for preparing oyster shell calcium granules - Google Patents

Abstract

A method for preparing oyster shell calcium granules, the method comprising the following steps: dissolving a prescribed amount of citric acid and some sucrose in an ethanol solution to prepare a solution A, adding a prescribed amount of oyster shell calcium and the remaining amount of sucrose to a wet granulator, then adding the solution A, performing shearing and granulating, and drying and size grading same. The prepared oyster shell calcium granules have the characteristics of good content uniformity, good solubility, low precipitation, stable pH value, etc.

Description

A kind of preparation method of oyster calcium carbonate particle technical field

The invention belongs to the field of pharmaceutical preparations, and in particular relates to a preparation method of oyster calcium carbonate granules.

Background technique

Calcium is one of the important elements of the human body and has very important physiological and biochemical functions. The content of calcium in the human body accounts for 1.5%-2% of the total body weight, of which bones and teeth account for about 99%, and body fluids and soft tissues account for 1%. Calcium is not only the main substance that constitutes bones, but also participates in the metabolism of bones, and is necessary to maintain nerve and muscle functions. It also plays a role in maintaining normal heart, kidney, lung and blood coagulation functions, as well as the permeability of cell membranes and capillaries. It can also regulate the secretion and storage of neurotransmitters and hormones, the uptake and utilization of amino acids, and the absorption of vitamin B12. An important mechanism for human living cells to obtain energy is the transmembrane movement of calcium. Usually, the calcium content of the cell membrane is 500 times higher than that of the intracellular calcium. Neuromuscular responses, blood coagulation, cell adhesion, nerve impulse conduction, heart rate maintenance, and cell secretion, contraction, excitation, diffusion, and differentiation all depend on this transmembrane movement. Oyster calcium carbonate is widely used in European and American countries, and has been recorded in Chinese, American, British, and Japanese pharmacopoeias, and it is clinically used as a calcium supplement.

People at all stages need to supplement enough calcium. Infants and young children grow and develop rapidly, which is the most vigorous stage of calcium metabolism in life. Once calcium deficiency occurs, a series of early symptoms will appear, such as irritability, sweating, anorexia, night terrors, and convulsions. If the early calcium deficiency is not corrected in time, it will lead to decreased autoimmunity, upper respiratory tract infection of unknown cause, frequent spasmodic abdominal pain and diarrhea, and children with thin and yellow hair, pillow baldness, annular baldness and other signs. Studies have shown that women with low calcium intake during pregnancy (an average of 478 mg per day) have a high absorption rate of calcium in their intestines, but their bone density (represented by lumbar spine bone density) is still significantly lower, which is comparable to that of non-pregnant women of the same age. Compared with women, the average drop was 15%. Pregnant women who consume more calcium (1274 mg per day on average), although their intestinal absorption rate of calcium is lower, their bone density does not decrease, which is basically the same as that of non-pregnant women of the same age. This shows that increasing calcium intake during pregnancy is the basic guarantee for the bone health of pregnant women, and the above evolutionary mechanism alone is far from enough. The metabolism of the elderly gradually slows down, the digestive function weakens, and the calcium requirement increases relatively.

The effect of calcium supplementation depends on how much calcium is absorbed. The absorption site of calcium is in the upper part of the small intestine, and the duodenum absorbs the fastest, but the absorption amount takes the longer ileum as the main absorption site of calcium. The absorption of calcium is mainly through the active transport of the intestinal mucosa, except for a small amount of absorption by diffusion. The absorption rate is different in different ages: the absorption rate of infants is the highest, 50%-60%; the absorption rate of teenagers is 35%-40%; the absorption rate of adults is lower, 15%-20%; the absorption rate of the elderly Only 10%. The concentration of the drug in the blood is an important condition for the drug to exert and maintain its curative effect, and it is also the basis for evaluating the absorption of calcium supplements.

Oyster Calcium Carbonate is a regular calcium supplement for pregnant and lactating women, menopausal women, the elderly, etc. The active ingredients of this product have extremely low solubility in water, and are prone to precipitation during storage and use. At this time, calcium does not exist in an ion state, and it needs to be absorbed after being dissociated by gastric acid. This condition can be irritating to the stomach and can also affect calcium absorption. "How to Correctly Choose Oral Calcium Agents" ("China Rural Medicine", 1998, Vol. 26, No. 1, Page 17), summarizes the characteristics that high-quality calcium agents should have, including good solubility and high bioavailability. For this product, how to improve the solubility of this product, reduce precipitation, and ensure the stability of quality indicators, so as to improve the calcium supplement effect of this product, has been an unsolved problem that pharmaceutical researchers have been working hard on.

CN106943427A discloses a calcium carbonate particle composition and a preparation method thereof to solve the problems of poor solubility and easy precipitation of existing preparations. The composition according to the scheme comprises: 100 parts of calcium carbonate, 3000-4500 parts of powdered sugar and 120-180 parts of acid source. The method includes the following steps:

(a) by weight ratio, weigh 100 parts of calcium carbonate, 3000-4500 parts of powdered sugar, 120-180 parts of acid source;

(b) Take 100-150 parts of powdered sugar and add purified water to prepare a syrup with a mass ratio concentration of 35-65%, mix the calcium carbonate and powdered sugar uniformly in a mass ratio of 100:900-2000, and then add the Said syrup is made into soft material, wet granulated, dried, and granulated to obtain calcium carbonate granules;

(c) mix the acid source and purified water according to the mass ratio of 1:0.4-1, add the remaining powdered sugar after fully dissolving, make a soft material, wet granulate, dry, and granulate to obtain acid granules;

(d) mixing the calcium carbonate granules obtained in step (b) and the acid granules obtained in step (c) to obtain the calcium carbonate granule composition.

In the above preparation method, the finished granules are divided into two parts, namely calcium carbonate granules and acid granules. Calcium carbonate granules are made by adding water to sucrose to make syrup, then granulated with calcium carbonate and powdered sugar; acid granules are made by adding acid to water, and then granulated with the remaining sucrose. By being divided into two parts, the contact between calcium carbonate and acid source is avoided to a certain extent, which is beneficial to the stability of calcium carbonate, improving solubility and reducing precipitation. In the technical scheme of the invention, step (c), that is, the acid particle drying step, adopts two methods: one is to dry for 5-60h at 25°C in a common drying oven; Dry with cold air for 1-20 minutes, then dry with hot air at 40-70°C for 10-20 minutes, then cool down to room temperature with cold air at 18-26°C. It can be seen that the drying of acid particles takes a long time (drying at 25°C for 5-60 hours), or the operation is cumbersome (first cold air, then hot air, and finally cold air drying), which increases the difficulty of operation and increases the production cost, which is not conducive to commercialization Production. In addition, during the process of reproducing the technical solution, the inventors found that the samples prepared by this method had two problems: 1. The content uniformity of the finished product was poor, which may be due to the small proportion of the main drug of this product (about 2.5% ), the use of two-part granulation is related to the fact that the main ingredient is not easy to mix evenly; 2. The results of further accelerated inspection and testing show that the acidity of the finished product has increased significantly.

Based on the pharmaceutical quality requirements of this product in clinical application and the defects in the existing technology, further research is necessary to ensure product quality, improve absorption, and improve clinical application effects. Oyster calcium carbonate granules mostly adopt wet granulation process. Specifically, rocking granulation, shear granulation, one-step fluidized bed granulation, and a combination of different granulation methods can be used. In the process of in-depth research on the process, the inventor improved the technical solution disclosed in CN106943427A, replaced the granulation solvent with purified water to a certain concentration of ethanol, dissolved citric acid in ethanol and then granulated with sucrose, and found that the obtained granules It will appear light yellow when drying, and the color will deepen with the increase of citric acid dosage. According to this phenomenon, the inventor creatively mixed sucrose and citric acid in ethanol solution, and the mixed solution was used as binder, and then granulated. Through the study of ethanol concentration, the amount of dissolved sucrose, and the corresponding conditions, it was found that the finished product prepared by this granulation method has better content uniformity, good solubility, less precipitation, and stable pH value. Surprisingly, by monitoring the blood calcium concentration after taking it, the finished product made by this process has a better calcium supplement effect and can increase the blood calcium concentration faster.

Contents of the invention

The object of the present invention is to provide a kind of preparation method of oyster calcium carbonate particle, this method adopts wet shearing granulation process. The outstanding substantive feature of this process is that ethanol is used as a solvent, and the entire prescription amount of citric acid and a specific amount of sucrose are dissolved in ethanol, and a specific temperature needs to be controlled during the dissolution.

A kind of preparation method of oyster calcium carbonate particle of the present invention comprises the following steps:

1) Oyster calcium carbonate and sucrose are pulverized through a 80-100 mesh sieve;

2) Take by weighing 6.5% of the weight of the granulated material an ethanol solution with a concentration of 20%-40%, and dissolve the prescription amount of citric acid and 6.5%-8.5% of the prescription amount of sucrose in the above-mentioned ethanol solution, and control the temperature of the ethanol solution during dissolution. 40°C-60°C to prepare solution A;

3) Add the prescription amount of oyster calcium carbonate and the remaining amount of sucrose into the wet granulator, stir and mix evenly, add the solution A in step 2), and shear granulate;

4) Drying, sizing and subpackaging the prepared granules to obtain oyster calcium carbonate granules.

The further optimized technical scheme of the present invention can be:

1) Oyster calcium carbonate and sucrose are crushed through a 100-mesh sieve;

2) The concentration of ethanol solution is 30%;

3) Ethanol solution dissolves 7.5% sucrose in prescription quantity;

4) When dissolving citric acid and sucrose, control the temperature of the ethanol solution to 50°C.

In addition, in the process of product preparation, after shear granulation, depending on the condition of the granulated material, an appropriate amount of ethanol solution can be added and then shear granulated, which can be judged by those skilled in the art based on experience.

In the preparation method of the present invention, the oyster calcium carbonate granule prescription contains parts by weight:

Oyster calcium carbonate 125 servings

Sucrose 4675-4710 parts

Citric acid 165-200 parts

Further, in the preparation method of the present invention, the prescription of oyster calcium carbonate granules contains parts by weight:

Oyster calcium carbonate 125 servings

Sucrose 4690 parts

Citric acid 185 parts

The prescription of the present invention may also contain other pharmaceutical excipients suitable for this dosage form, including pigments and essences, such as 0.1 part of tartrazine and 2.5 parts of orange essence.

In the preparation method of the present invention, oyster calcium carbonate and sucrose are pulverized and passed through a sieve of 80-100 mesh, preferably a sieve of 100 mesh, and the sieving treatment realizes the particle size control of the starting material and avoids material agglomeration. When using other sizes of screens, there is also the possibility of application, but it will increase the risk of product quality and increase the cost. Solution A prepared by dissolving citric acid and part of sucrose in ethanol solution acts as a binder during the preparation of this product. According to research, the amount of ethanol solution is 6.5% of the weight of the granulated material. In the preparation method of the present invention, after the granulation is completed, a small amount of ethanol can be added according to the state of the material, and then the granulation can be carried out. This is a problem that can be recognized and judged by ordinary technicians in pharmacy, and it will not have a major or decisive impact on the quality of this product.

Below in conjunction with prior art literature, the positive effect that the present invention has is described:

In the prescription of oyster calcium carbonate granules, there are many acid sources, such as citric acid. Calcium carbonate is alkaline, while citric acid is acidic, and they may react upon contact to form calcium citrate precipitates. Avoiding the contact between the two during the production process can reduce the reaction and precipitation, and further help to increase absorption and improve the effect of calcium supplementation. In the technical solution disclosed in CN106943427A, the finished granules are divided into two parts, namely calcium carbonate granules and acid granules. By being divided into two parts, the contact between calcium carbonate and acid source is avoided to a certain extent, which is beneficial to the stability of calcium carbonate, improving solubility and reducing precipitation. The present invention uses ethanol as a solvent, and creatively dissolves the whole prescription amount of citric acid and part of sucrose in ethanol. The ethanol concentration is obtained through screening and needs to be controlled at 20%-40%, and the preferred ethanol concentration is 30%. The amount of sucrose dissolved in ethanol is determined after repeated screening, and the stability of this product can only be guaranteed if the amount reaches 6.5% of the weight of the granulated material. When the dosage is lower than 6.5%, there is no obvious difference in the quality of the finished product at day 0, but in the process of drug stability investigation, there will be problems of increased precipitation and increased pH value. When the amount of sucrose is higher than 8.5% by weight of the granulated material, the problem of slow dissolution process of sucrose will occur, which is not conducive to industrial production. In the preparation method of the present invention, the preferred amount of sucrose dissolved in ethanol is 7.5% of the recipe amount. In the process of dissolving citric acid and part of sucrose in ethanol, the temperature of ethanol needs to be controlled at 40°C-60°C. Below 40°C, the material dissolves slowly, which is not conducive to production; above 60°C, the color of the prepared particles is prone to change, which needs to be avoided during the production process. The finished product prepared by the method of the invention weakens the effect of citric acid and calcium carbonate, thereby having the characteristics of good solubility, less precipitation and stable pH value. In addition, this method adopts wet granulation to fully mix and evenly, and the content uniformity of the finished product is better. Surprisingly, by monitoring the blood calcium concentration after taking it, the blood calcium concentration can be increased faster and has a better calcium supplement effect. For calcium supplement products, increasing absorption and improving effects have always been the direction of continuous efforts of technicians.

The technical solution of the present invention is essentially characterized in that citric acid and a specific amount of sucrose are dissolved in an alcoholic solution for granulation, and a conventional wet granulation process is still adopted. The production process is simple, the operation is easy, the cost is low, and it is suitable for large-scale industrial production. The preparation method not only ensures the product quality in pharmacy, but also has better clinical application effect. The present invention is undoubtedly a huge technical progress for the calcium supplement product of oyster calcium carbonate granules, and also has a significant improvement compared with the prior art.

Detailed ways

The following examples are only used to further illustrate the present invention in detail, but do not limit the scope of the present invention in any way.

Embodiment 1: oyster calcium carbonate granule prescription (parts by weight)

Oyster carbon calcium carbonate 125 servings

Sucrose 4690 parts

Citric acid 185 parts

Preparation:

1) Pulverize oyster calcium carbonate and sucrose through a 100-mesh sieve.

2) Take by weighing 30% ethanol solution with a concentration of 6.5% of the weight of the granulation material, dissolve the prescription amount of citric acid and 7.5% prescription amount of sucrose in the ethanol solution, stir and heat when dissolving, and control the temperature of the ethanol solution to 50°C. Solution A was prepared.

3) Add the prescription amount of oyster calcium carbonate and the remaining amount of sucrose into the high-efficiency wet granulator, stir at a low speed for 100 seconds, and mix well. Then add the solution A in step 2) with low-speed stirring and high-speed cutting. After adding solution A, high-speed stirring and high-speed cutting for 60 seconds to obtain wet particles.

4) The prepared granules are dried in a fluidized bed, and the air inlet temperature is controlled at about 60° C. during drying; the dried granules are sized with a pulverizing granulator.

5) Hermetically packaged in a medicinal composite film bag (calculated as calcium 50 mg/bag), to obtain oyster calcium carbonate granules.

Embodiment 2: oyster calcium carbonate granule prescription (parts by weight)

1) Pulverize oyster calcium carbonate and sucrose through an 80-mesh sieve.

2) Take by weighing the 20% ethanol solution with a concentration of 6.5% of the weight of the granulation material, dissolve the prescription amount of citric acid, the prescription amount of tartrazine and the prescription amount of 6.5% sucrose in the ethanol solution, stir and heat when dissolving, and control the ethanol Solution A was prepared at a solution temperature of 40°C.

3) Add the prescription amount of oyster calcium carbonate and the remaining amount of sucrose into the high-efficiency wet granulator, stir at a low speed for 100 seconds, and mix well. Then add the solution A in step 2) with low-speed stirring and high-speed cutting. After adding solution A, high-speed stirring and high-speed cutting for 60 seconds to obtain wet particles.

4) The prepared granules are dried in a fluidized bed, and the air inlet temperature is controlled at about 60° C. during drying; the dried granules are sized with a pulverizing granulator.

5) Hermetically packaged in a medicinal composite film bag (calculated as calcium 50 mg/bag), to obtain oyster calcium carbonate granules.

Embodiment 3: oyster calcium carbonate granule prescription (weight part)

1) Pulverize oyster calcium carbonate and sucrose through a 100-mesh sieve.

2) Take by weighing 40% ethanol solution with a concentration of 6.5% of the weight of the granulation material, dissolve the prescription amount of citric acid, the prescription amount of orange essence and the prescription amount of 8.5% sucrose in the ethanol solution, stir and heat during dissolution, and control the ethanol The solution temperature is 60°C, and the solution A is prepared.

3) Add the prescription amount of oyster calcium carbonate and the remaining amount of sucrose into the high-efficiency wet granulator, stir at a low speed for 100 seconds, and mix well. Then add solution A in step 2) with low-speed stirring and high-speed cutting, and high-speed stirring and high-speed cutting for 60 seconds after solution A is added. After the granulation is completed, turn on low-speed stirring and high-speed cutting, then weigh 40% ethanol solution according to 1% of the weight of the granulated material and add it, after adding the ethanol solution, high-speed stirring and high-speed cutting for 30 seconds, that is, wet granules.

4) The prepared granules are dried in a fluidized bed, and the air inlet temperature is controlled at about 60° C. during drying; the dried granules are sized with a pulverizing granulator.

5) Hermetically packaged in a medicinal composite film bag (calculated as calcium 50 mg/bag), to obtain oyster calcium carbonate granules.

Comparative Example 1: According to the content disclosed in Example 1 of CN106943427A, a sample was prepared.

1) Oyster calcium carbonate and sucrose are passed through an 80-mesh sieve respectively, and 75.2 g of sieved oyster calcium carbonate powder, 2809 g of sieved sucrose powder, 115.8 g of citric acid, and 0.044 g of tartrazine are weighed;

2) Get 93.5g of sucrose powder and add purified water to be mixed with a mass ratio concentration of 50% syrup, put 75.2g of sieved oyster calcium carbonate and 1425g of white granulated sugar powder into manual sieving and mix for 3 times, then add syrup and The pigment aqueous solution prepared by dissolving 0.022g of pigment in 10g of purified water is made into a soft material, wet granulated, dried at 50°C for 120min, and granulated to obtain calcium carbonate granules;

3) Mix 115.8g of citric acid with 47g of purified water, fully dissolve it, add the remaining powdered sugar and dissolve 0.022g of pigment in 10g of purified water to make a soft material, wet granulate, dry at 25°C for 16 hours, and granulate , to get acid particles.

4) Mix the calcium carbonate granules obtained in step (2) and the acid granules obtained in step (3).

5) Hermetically packaged in a medicinal composite film bag (calculated as calcium 50 mg/bag), to obtain oyster calcium carbonate granules.

Comparative test: the finished calcium carbonate granules prepared in Examples 1-3 of the present invention and the finished calcium carbonate granules prepared in the comparative examples were detected. When testing, refer to the national drug standard WS-10001-(HD-1037)-2002 for testing.

Content: get respectively 10 bags of finished products prepared in Examples 1-3 and Comparative Example 1, grind the granules finely, accurately weigh an appropriate amount (approximately equivalent to 50 mg of calcium), put in a 100 ml measuring bottle, add 100 ml of dilute hydrochloric acid, and shake to make Dissolve, add 0.1g of activated carbon, shake fully, dilute to the mark with water, shake well, filter, accurately measure 50ml of the subsequent filtrate, add 50ml of water, 1 drop of methyl red indicator solution, add dropwise ammonia test solution to make the solution change from red to If it is slightly yellow, add 5ml of triethanolamine solution (1-5), shake well, add 18ml of sodium hydroxide test solution, 0.2g of calpurin indicator, and use disodium edetate titration solution (0.05mol/L) Titrate until the solution turns from purple red to pure blue, and every 1ml of disodium edetate titration solution (0.05mol/L) is equivalent to 2.004mg of Ca.

Acidity: Take an appropriate amount of fine powder of this product (approximately equivalent to 50mg of calcium), add 100ml of water, shake for 10 minutes, and filter. Get filtrate, measure according to law (Chinese Pharmacopoeia edition in 2000 two appendix VI H), pH value should be 4.5-6.5.

Solubility: Take 10g of this product, heat 200ml of water, stir for 5 minutes, it should be completely dissolved or slightly turbid or evenly suspended, but there should be no foreign matter such as burnt debris.

Content uniformity: take 10 bags of the finished product, check the content of each bag according to the detection method of the content item, and calculate the RSD.

(1) 0-day detection: the calcium carbonate granule finished product prepared by embodiment 1-3 and the calcium carbonate granule finished product prepared by comparative example 1 are tested for content, acidity, solubility, content uniformity, and its test results are shown in Table 1.

Table 1 The 0-day performance test of the products prepared in Examples 1-3 and Comparative Example 1

sample	content/%	AciditypH	Solubility	Content Uniformity (RSD)
Example 1	100.2	5.06	melt all, clear	0.96%
Example 2	99.3	5.12	melt all, clear	0.83%
Example 3	99.8	4.83	melt all, clear	0.78%
Comparative example 1	99.5	4.96	melt all, clear	4.25%

Result evaluation: the oyster calcium carbonate granules prepared by Examples 1-3 and Comparative Example 1 had no significant difference in the main detection index content, acidity, and solubility on day 0; the content uniformity item, the embodiment sample was obviously better than the comparative example sample.

(2) Accelerate 3 months detection: with the calcium carbonate granule finished product prepared by embodiment 1-3 and the calcium carbonate granule finished product prepared by comparative example 1, at 40 ℃, under the condition of 75% humidity, accelerate investigation 3 months, carry out correlation The test results are shown in Table 2.

Table 2 Accelerated detection results in three months after the products prepared in Examples 1-3 and Comparative Example 1 were packaged

sample	content/%	acidity	Solubility
Example 1	100.5	5.02	melt all, clear
Example 2	99.7	5.13	melt all, clear

Example 3	99.1	4.85	melt all, clear
Comparative example 1	99.9	5.23	melt all, clear

Result evaluation: the oyster calcium carbonate granules prepared in Examples 1-3, after accelerating for 3 months, there is no significant difference in the main detection indicators between batches, and there is no significant change compared with 0 days. For the oyster calcium carbonate particles prepared in Comparative Example 1, the acidity items increased to a certain extent compared with 0 days.

(3) Accelerate 6 months detection: with the calcium carbonate granule finished product prepared by embodiment 1-3 and the calcium carbonate granule finished product prepared by comparative example, at 40 ℃, under the condition of 75% humidity, accelerate investigation 6 months, carry out relevant detection , and the test results are shown in Table 3.

Table 3 embodiment 1-3 and comparative example 1 preparation product packaging back accelerated testing result in June

sample	content/%	acidity	Solubility
Example 1	100.0	5.06	melt all, clear
Example 2	100.2	5.17	melt all, clear
Example 3	99.4	4.88	melt all, clear
Comparative example 1	99.1	6.06	slightly cloudy

Result evaluation: the oyster calcium carbonate granules prepared in Examples 1-3, after accelerating for 6 months, there is no significant difference in the main detection indicators between batches, and there is no significant change compared with the 0 day. For the oyster calcium carbonate granules prepared in Comparative Example 1, the acidity item increased significantly compared with 0 day; the solubility item also changed from all melting clarification to slight turbidity.

According to the test results on day 0, the content uniformity of the samples of the examples is obviously better than that of the samples of the comparative examples. According to the inspection results of accelerated March and accelerated June, compared with the sample of the comparative example, the sample of the embodiment has better acidity stability, and the solubility index is also better than that of the sample of the comparative example.

Calcium Supplement Efficacy Evaluation

The finished product of oyster calcium carbonate granules (calculated as calcium 50 mg/bag) prepared in Example 2 and Comparative Example 1 is used for calcium supplementation crowds, blood calcium concentration is monitored before and after taking, and clinical application effect is evaluated.

Volunteer grouping and methods: Screen 98 cases who are suitable for calcium supplementation or have calcium supplementation needs, and randomly divide them into two groups, 49 cases in each group. Group I took the oyster calcium carbonate granules of Example 2, and Group II took the oyster calcium carbonate granules of Comparative Example 1. The two groups took the same method: take it orally, two bags at a time, three times a day, and take it with warm water. Both groups were taken continuously for 8 weeks. Venous blood was drawn at the following time points for blood calcium concentration monitoring, and the data was recorded and analyzed: before taking, after taking for 4 weeks, after taking for 6 weeks, and after taking for 8 weeks.

Table 4 Comparison of blood calcium concentration before and after taking the finished product of Example 2 and Comparative Example 1

Result evaluation: From the monitoring of blood calcium concentration, it can be seen that the blood calcium concentration at each monitoring time point is higher than that of Comparative Example 1 after taking the oyster carbon calcium granules of Example 2. In particular, the blood calcium concentration of Example 2 taken for 6 weeks is basically close to that of the control group 1 taken for 8 weeks. Therefore, the oyster calcium carbonate granule of the present invention can increase the blood calcium concentration faster and has a better calcium supplement effect.

Claims (7)

1. A preparation method for oyster calcium carbonate particles, comprising the following steps:

   1) Oyster calcium carbonate and sucrose are pulverized through a 80-100 mesh sieve;

   2) Take the ethanol solution with a concentration of 20%-40% by weighing 6.5% of the weight of the granulation material, dissolve the prescribed amount of citric acid and 6.5%-8.5% of the prescribed amount of sucrose in the above-mentioned ethanol solution, and control the ethanol solution when dissolving The temperature is 40°C-60°C to prepare solution A;

   3) Add the prescription amount of oyster calcium carbonate and the remaining amount of sucrose into the wet granulator, stir and mix evenly, add the solution A in step 2), and shear granulate;

   4) Drying, sizing and subpackaging the prepared granules to obtain oyster calcium carbonate granules.
2. The method according to claim 1, wherein the mesh sieve is 100 mesh.
3. The method according to claim 1, characterized in that the concentration of the ethanol solution is 30%.
4. The method according to claim 1, characterized in that the sucrose in step 2) is specifically 7.5% of the prescription amount.
5. The method according to claim 1, characterized in that the temperature of the ethanol solution is specifically 50°C.
6. The method according to claim 1, the oyster calcium carbonate granule prescription contains by weight:

   Oyster calcium carbonate 125 servings

   Sucrose 4675-4710 parts

   Citric acid 165-200 parts
7. The method according to claim 1, the oyster calcium carbonate granule prescription contains by weight:

   Oyster calcium carbonate 125 servings

   Sucrose 4690 parts

   Citric acid 185 parts