Compound preparation of calcium citrate casein phosphopeptide calcium tablets and preparation method of compound preparation

Abstract

The invention discloses a compound preparation of calcium citrate casein phosphopeptide calcium tablets and a preparation method of the compound preparation. The compound preparation comprises the following components in percentage by weight: 90-96% of calcium citrate particles, 0.68-1.84% of casein phosphopeptide, 0.08-0.16% of vitamin D3 powder, 0.7-1.5% of vitamin K2 powder, 0.5-1.5% of sodium carboxymethyl starch and 0.6-1.0% of magnesium stearate. And 2-4% of a coating premix. The preparation method comprises the following steps: step 1, calcium citrate wet granulation; step 2, mixing; step 3, tabletting; step 4, coating; the feed is reasonable in matching and balanced in proportioning, and can supplement calcium, vitamin D and vitamin K. The compound preparation of the calcium citrate casein phosphopeptide calcium tablet can effectively avoid gastrointestinal discomfort and prevent constipation while improving the effective rate of calcium supplement. In addition, the compound preparation of the calcium citrate casein phosphopeptide calcium tablet is good in taste, convenient to carry, easy in raw material obtaining and low in production cost.

Description

Technical Field

[0001] The present invention relates to the technical field of compound preparations, and in particular to a compound preparation which is prepared with calcium citrate, casein phosphopeptide, vitamin D3 powder and vitamin K2 powder as main raw materials and auxiliary materials such as maltodextrin and can supplement calcium, vitamin D and vitamin K, and a preparation method thereof. Background Art

[0002] Calcium citrate, also known as calcium citrate, is a type of organic calcium. It is mostly used in the food field and is often used as a calcium fortifier, chelating agent, buffer and tissue coagulant. Especially as a calcium fortifier, it is often added to infant formula, beverages, milk and various health products because of its mild taste and high calcium content.

[0003] Bone health problems are no longer a problem for middle-aged and elderly people, but are becoming more and more common among younger people. Osteoporosis is a systemic bone disease caused by a variety of reasons, including decreased bone density and quality, destruction of bone microstructure, increased bone brittleness, and easy fractures. Osteoarthritis is a degenerative disease caused by factors such as aging, obesity, strain, trauma, congenital abnormalities of joints, and joint deformities, resulting in degenerative damage to articular cartilage, reactive hyperplasia of joint margins and subchondral bone, also known as osteoarthritis, degenerative arthritis, senile arthritis, hypertrophic arthritis, etc. Clinical manifestations include slowly developing joint pain, tenderness, stiffness, joint swelling, limited movement, and joint deformities.

[0004] There are about 200 million people with bone problems worldwide, and more than 8.9 million fractures occur due to osteoporosis each year, of which 80% are women over 50 years old; there are 360 ​​million osteoarthritis patients, with a disability rate of 53%; the number of people with cervical spine diseases is as high as 900 million, ranking second in the "Top Ten Intractable Diseases in the World" announced by the WHO; about 49% of the residents in my country have worrying bone health conditions, of which more than 90 million are osteoporosis patients, and the incidence rate in people over 50 years old is about 15.7%; there are more than 100 million osteoarthritis patients; the number of cervical spine patients is as high as 120 million, and it is constantly showing an upward trend.

[0005] Calcium deficiency affects the normal life of human beings, especially children and the elderly. Calcium deficiency not only causes rickets in children and osteoporosis in adults, but is also related to diseases such as structural cancer and hypertension. The Chinese Nutrition Society recommends that the daily dietary calcium intake for children is 600-800 mg and for adults is 800 mg. According to the 2015 National Nutrition Survey "Average Intake of Energy and Major Nutrients of Chinese Residents", the daily calcium intake is only 356.3 mg, which is only 50% of the recommended intake. Therefore, calcium supplementation is of great significance.

[0006] The absorption rate of calcium depends on: ① The body's need for calcium: such as children in the growth and development period, women in pregnancy and lactation, ② The total calcium intake: when the calcium intake is low, the absorption rate is higher, ③ The type of food: The food factors that are conducive to the absorption and utilization of calcium are mainly: vitamin D, acidic medium, protein, lactose. If the human body is calcium deficient for a long time, the blood calcium level will drop, affecting normal metabolism, causing the growth of long bones to stagnate, and inducing a variety of diseases. Common diseases include rickets in children and osteoporosis in adults. In addition, calcium deficiency can also cause hyperparathyroidism and cause various symptoms of weakness and maladaptation, such as loss of appetite, muscle cramps, and memory loss. At present, some scholars believe that one of the important causes of hypertension, pregnancy-induced hypertension syndrome, postpartum weakness, menopausal syndrome, etc. is also calcium deficiency. In summary, it is necessary to supplement the human body with an appropriate amount of calcium from the perspective of prevention and health care.

[0007] The calcium source of traditional calcium supplements is calcium carbonate, which can easily cause gastrointestinal discomfort and constipation after taking. In addition, the calcium supplement efficiency of taking calcium carbonate alone is relatively low. Summary of the invention

[0008] The purpose of the present invention is to provide a compound preparation of calcium citrate casein phosphopeptide calcium tablets capable of supplementing nutrients such as calcium, vitamin D, vitamin K and the like and a preparation method thereof, thereby solving the above technical problems.

[0009] In order to achieve the above technical objectives and meet the above technical requirements, the present invention uses calcium citrate and calcium accelerator as main ingredients, and promotes calcium absorption and relieves gastrointestinal discomfort through the calcium accelerator, thereby improving the efficiency of calcium supplementation and avoiding gastrointestinal discomfort and constipation.

[0010] A calcium citrate casein phosphopeptide calcium tablet comprises a main ingredient and auxiliary ingredients.

[0011] The main ingredients include: calcium citrate and calcium accelerator.

[0012] The auxiliary materials include: fillers, binders, disintegrants, lubricants and coating premixes.

[0013] Preferably, the content of calcium citrate is 75.6-86.4 wt %.

[0014] Preferably, the content of the calcium accelerator is 1.46-3.5 wt %.

[0015] The calcium accelerator includes casein phosphopeptide, vitamin D3 powder and vitamin K2 powder.

[0016] Casein phosphopeptides (CPPs) are biologically active peptides obtained through biotechnology using bovine casein as raw material and hydrolyzed by single or combined proteases. Under alkaline conditions, CPPs can prevent the precipitation of calcium, iron and other ions, thereby promoting their absorption, so CPPs are called "mineral carriers". With the promotion and application of calcium fortifiers, CPPs have been widely used in calcium-fortified dairy products, fruit juice drinks, protein drinks and instant drinks, sports foods, candies, nutrient supplements and anti-caries chewing gum in Japan, Southeast Asia, Europe, Australia and other places. my country has now widely used CPPs as food additives in infant formula, mineral supplement foods such as calcium, iron and zinc, and nutritional compound preparations. There are many studies on CPPs promoting calcium absorption at home and abroad, among which the mechanism of promoting calcium absorption has become increasingly clear. Calcium must be absorbed in the form of ions in the intestine. In the anterior segment of the small intestine, vitamin D can enhance the active absorption of calcium in the anterior segment of the small intestine as a calcium absorption promoter. In the posterior part of the small intestine, calcium is absorbed by passive diffusion, and the absorption efficiency depends on the free concentration of calcium ions in the small intestine. However, calcium ions easily form insoluble salts with acid ions in a neutral and weakly alkaline environment and are lost.

[0017] Vitamin D is a colorless crystal that is soluble in fat, lipid solvents and organic solvents. It has stable chemical properties, is heat-resistant in neutral and alkaline solutions, and is not easily oxidized, but gradually decomposes in acidic solutions. Vitamin D has the function of maintaining the balance of calcium and phosphorus metabolism. Vitamin D deficiency can cause rickets, osteomalacia and osteoporosis. According to the European Journal of Clinical Nutrition, a survey of residents in early spring showed that people of all ages have vitamin D deficiency. Supplementing calcium and vitamin D at the same time can reduce bone loss and prevent fractures. In addition, vitamin D also has other physiological functions. Studies have shown that vitamin D is an important substance to ensure the normal secretion of insulin by pancreatic B cells. Vitamin D supplementation can reduce the risk of type 1 diabetes in children; it can also effectively reduce blood lipid concentration and reduce the risk of cardiovascular disease for obese women; vitamin D supplementation can effectively prevent and treat breast cancer. It can be seen that in addition to preventing and treating osteoporosis, vitamin D supplementation can also prevent and treat the occurrence and development of many chronic diseases.

[0018] Vitamin K compounds belong to fat-soluble vitamins, and their basic structure is 2-methyl-1,4-naphthoquinone. Naturally occurring vitamins can be divided into vitamin K1 and vitamin K2 according to their side chain forms, and are widely present in nature. Vitamin K2 is a series of compounds, which are pale yellow crystals and are mainly synthesized by intestinal bacteria; there are 14 forms according to the length of the isoprene side chain on C-3, represented by MK-n, where n refers to the number of isoprene units on the side chain. All are heat-resistant, but sensitive to light and alkali. Vitamin K participates in bone metabolism and is a promoter of bone formation. Clinical and experimental studies have shown that it has a clear anti-osteoporosis effect. Vitamin K2 is a key factor in human calcium regulation. Without vitamin K2, calcium regulation will be interrupted. Vitamin K2 is a dependent coenzyme for the synthesis of γ-carboxylated glutamate protein in bone cells. It promotes bone mineralization by increasing the carboxylation of osteocalcin. Uncarboxylated osteocalcin has no calcium binding activity. Vitamin K2 deficiency leads to decreased bone density and is an independent risk factor for osteoporosis. Animal and human clinical trials have confirmed that vitamin K2 improves bone structure, increases bone mass, bone density and mechanical strength, stimulates mineralization (calcium deposition) and improves bone collagen structure, optimizes calcium balance and inhibits bone loss. Vitamin K2 has been proven to be safe and has no side effects even at high doses. Most people can only get a small amount of vitamin K2 from food, so vitamin K2 is the first choice for vitamin K supplements. Pregnant women and nursing mothers need to supplement vitamin K because babies cannot synthesize vitamin K on their own, but vitamin K can promote the normal coagulation of the baby's blood and the growth of bones. Vitamin K supplementation can effectively reduce the chance of intracranial hemorrhage and gastrointestinal bleeding in babies.

[0019] The bulking agent includes maltodextrin.

[0020] The binder includes edible corn starch.

[0021] The disintegrant includes sodium carboxymethyl starch.

[0022] The lubricant includes magnesium stearate.

[0023] The coating premix includes premixed coating powders such as polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talcum powder.

[0024] The technical scheme adopted by the present invention is: a compound preparation of calcium citrate casein phosphopeptide calcium tablets and a preparation method thereof, wherein the compound preparation comprises the following components in weight percentage: 90-96% calcium citrate particles, 0.68-1.84% casein phosphopeptide, 0.08-0.16% vitamin D3 powder, 0.7-1.5% vitamin K2 powder, 0.5-1.5% sodium carboxymethyl starch, 0.6-1.0% magnesium stearate; and 2-4% coating premix.

[0025] As a preferred technical solution: the calcium citrate particles are composed of the following components in weight percentage: 84-90% calcium citrate, 6-11% maltodextrin, and 4-5% edible corn starch.

[0026] As a preferred technical solution: the mesh size of the calcium citrate is 100-1500 mesh.

[0027] A method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets, characterized in that it comprises the following steps:

[0028] Step 1: Calcium citrate wet granulation

[0029] Step 2: Mixing;

[0030] Step 3: pressing into tablets;

[0031] Step 4: Coating

[0032] As a preferred technical solution: in step 1, calcium citrate and maltodextrin are mixed, and corn starch and an appropriate amount of water are used to prepare a slurry with a concentration of 8-15%, and the mixture is heated to fully dissolve into starch slurry, and the mixture is put into a wet granulator and stirred for 1-10 minutes to mix well.

[0033] As a preferred technical solution: in step 2, the calcium citrate particles are fully mixed with other components except the coating premix.

[0034] As a preferred technical solution: in step 3, the tablets are pressed using a high-speed rotary tablet press.

[0035] As a preferred technical solution: in the step 4, a coating premix solution is prepared with a concentration of 10-20%, and the tablets prepared in the step 3 are coated.

[0036] The invention has the beneficial effects of providing a compound preparation of calcium citrate casein phosphopeptide calcium tablets and a preparation method thereof. Compared with the traditional method, calcium citrate and casein phosphopeptide with extremely fine mesh, vitamin D3 and vitamin K2 are added. In addition to the advantages of calcium citrate having a calcium supplementing effect and good absorption, casein phosphopeptide, vitamin D and vitamin K synergistically promote the absorption and utilization of calcium by the human body; the combination is reasonable and the ratio is balanced, calcium, vitamin D and vitamin K can be supplemented, osteoporosis, arthritis, and bone health can be improved, and gastrointestinal discomfort symptoms can be avoided and constipation can be prevented. DETAILED DESCRIPTION

[0037] The present invention is further described below;

[0038] Example 1

[0039] A compound preparation of calcium citrate casein phosphopeptide calcium tablets comprises the following components in weight percentage: 95.42% calcium citrate granules, 0.7% casein phosphopeptide, 0.08% vitamin D3 powder, 0.7% vitamin K2 powder, 0.5% sodium carboxymethyl starch, 0.6% magnesium stearate; and 2% coating premix.

[0040] The calcium citrate particles are composed of the following components in weight percentage: 84% calcium citrate, 11% maltodextrin, and 5% edible corn starch.

[0041] The mesh number of the calcium citrate is 100-1500 meshes, and the ratio is 1:1.

[0042] A method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets, characterized in that it comprises the following steps:

[0043] Step 1: Wet granulation of calcium citrate: Mix calcium citrate and maltodextrin, prepare a slurry with a concentration of 8% with corn starch and an appropriate amount of water, heat it to fully dissolve it into starch slurry, put the mixed material into a wet granulator, stir for 3 minutes, and mix well.

[0044] Step 2: Mixing: Mix the calcium citrate granules thoroughly with the other components except the coating premix.

[0045] Step 3: Compress into tablets: Use a high-speed rotary tablet press to compress into tablets.

[0046] Step 4: Coating: Prepare a coating premix solution with a concentration of 15% and coat the tablets prepared in step 3.

[0047] Calcium citrate granules 954.2g, casein phosphopeptide 7g, vitamin D3 powder 0.8g, vitamin K2 powder 7g, sodium carboxymethyl starch 5g, magnesium stearate 6g; coating premix 20g, according to the preparation method, first granulate and then mix and press to form tablets, and finally coat, which can improve osteoporosis, arthritis, promote bone health, and has good absorption.

[0048] Example 2

[0049] A compound preparation of calcium citrate casein phosphopeptide calcium tablets comprises the following components in weight percentage: 93.45% calcium citrate granules, 1.1% casein phosphopeptide, 0.1% vitamin D3 powder, 1% vitamin K2 powder, 0.9% sodium carboxymethyl starch, 0.75% magnesium stearate; and 2.7% coating premix.

[0050] The calcium citrate particles are composed of the following components in weight percentage: 86% calcium citrate, 9.4% maltodextrin, and 4.6% edible corn starch.

[0051] The mesh number of the calcium citrate is 100-1500 meshes, and the ratio is 1:1.

[0052] A method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets, characterized in that it comprises the following steps:

[0053] Step 1: Wet granulation of calcium citrate: Mix calcium citrate and maltodextrin, prepare a 10% slurry with corn starch and an appropriate amount of water, heat it to fully dissolve it into starch slurry, put the mixture into a wet granulator, stir for 6 minutes, and mix well.

[0054] Step 2: Mixing: Mix the calcium citrate granules thoroughly with the other components except the coating premix.

[0055] Step 3: Compress into tablets: Use a high-speed rotary tablet press to compress into tablets.

[0056] Step 4: Coating: Prepare a coating premix solution with a concentration of 15% and coat the tablets prepared in step 3.

[0057] Calcium citrate granules 933.8g, casein phosphopeptide 11g, vitamin D3 powder 1g, vitamin K2 powder 10g, sodium carboxymethyl starch 9g, magnesium stearate 7.5g; coating premix 27g, according to the preparation method, first granulate and then mix and press to form tablets, and finally coat, which can improve osteoporosis, arthritis, promote bone health, and has good absorption.

[0058] Embodiment 3:

[0059] A compound preparation of calcium citrate casein phosphopeptide calcium tablets comprises the following components in weight percentage: 91.77% calcium citrate granules, 1.5% casein phosphopeptide, 0.13% vitamin D3 powder, 1.2% vitamin K2 powder, 1.2% sodium carboxymethyl starch, 0.9% magnesium stearate; and 3.3% coating premix.

[0060] The calcium citrate particles are composed of the following components in weight percentage: 88% calcium citrate, 7.7% maltodextrin, and 4.3% edible corn starch.

[0061] The mesh number of the calcium citrate is 100-1500 meshes, and the ratio is 1:1.

[0062] A method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets, characterized in that it comprises the following steps:

[0063] Step 1: Wet granulation of calcium citrate: Mix calcium citrate and maltodextrin, prepare a slurry with a concentration of 12% with corn starch and an appropriate amount of water, heat it to fully dissolve it into starch slurry, put the mixture into a wet granulator, stir for 8 minutes, and mix well.

[0064] Step 2: Mixing: Mix the calcium citrate granules thoroughly with the other components except the coating premix.

[0065] Step 3: Compress into tablets: Use a high-speed rotary tablet press to compress into tablets.

[0066] Step 4: Coating: Prepare a coating premix solution with a concentration of 15% and coat the tablets prepared in step 3.

[0067] Calcium citrate granules 917.7g, casein phosphopeptide 15g, vitamin D3 powder 1.3g, vitamin K2 powder 12g, sodium carboxymethyl starch 12g, magnesium stearate 9g; coating premix 33g, according to the preparation method, first granulate and then mix and press to form tablets, and finally coat, which can improve osteoporosis, arthritis, promote bone health, and has good absorption.

[0068] Embodiment 4:

[0069] A compound preparation of calcium citrate casein phosphopeptide calcium tablets comprises the following components in weight percentage: 90.04% calcium citrate granules, 1.8% casein phosphopeptide, 0.16% vitamin D3 powder, 1.5% vitamin K2 powder, 1.5% sodium carboxymethyl starch, 1% magnesium stearate; and 4% coating premix.

[0070] The calcium citrate particles are composed of the following components in weight percentage: 90% calcium citrate, 6% maltodextrin, and 4% edible corn starch.

[0071] The mesh number of the calcium citrate is 100-1500 meshes, and the ratio is 1:1.

[0072] A method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets, characterized in that it comprises the following steps:

[0073] Step 1: Wet granulation of calcium citrate: Mix calcium citrate and maltodextrin, prepare a slurry with a concentration of 15% with corn starch and an appropriate amount of water, heat it to fully dissolve it into starch slurry, put the mixed material into a wet granulator, stir for 10 minutes, and mix well.

[0074] Step 2: Mixing: Mix the calcium citrate granules thoroughly with the other components except the coating premix.

[0075] Step 3: Compress into tablets: Use a high-speed rotary tablet press to compress into tablets.

[0076] Step 4: Coating: Prepare a coating premix solution with a concentration of 15% and coat the tablets prepared in step 3.

[0077] Calcium citrate granules 900.4g, casein phosphopeptide 18g, vitamin D3 powder 1.6g, vitamin K2 powder 15g, sodium carboxymethyl starch 15g, magnesium stearate 10g; coating premix 4g, according to the preparation method, first granulate and then mix and press to form tablets, and finally coat, which can improve osteoporosis, arthritis, promote bone health, and has good absorption.

[0078] Test Example 1

[0079] Calcium absorption promotion test: 5-week-old male KM mice (SPF level) were used for testing after being adapted to the test for 1 week. Specifically: At 9 o'clock in the evening on the day before the test, the mice were fasted but not watered. At 8 o'clock in the morning of the next day, the mice were randomly divided into five groups, with 10 mice in each group. Among them, one group was gavaged with normal saline as the control group, and the remaining four groups were gavaged with the aqueous dispersion of the compound preparation of calcium citrate casein phosphopeptide calcium tablets prepared in Examples 1-4 (dosage was 0.5g / kg body weight). Blood was collected from each group of mice 0 hour before and 1 hour after gavage, and serum was obtained by centrifugation to measure the calcium ion concentration in the serum. After administration, each group of mice was fasted but not watered.

[0080] Table 1 Test results for promoting calcium absorption

[0081] SPSS analysis showed that compared with the control group, *P<0.05, which was statistically significant.

[0082] Test Example 2

[0083] Effect evaluation: 160 subjects who needed calcium supplementation were randomly divided into 4 groups, 40 in each group, for clinical evaluation. The subjects took the compound preparation of calcium citrate casein phosphopeptide calcium tablets once a day, 3 tablets each time, for a total of three consecutive months.

[0084] Table 2 Results of taking effect evaluation test

[0085] It can be seen from the test results that the compound preparation of calcium citrate casein phosphopeptide calcium tablets of the present invention is not only easily absorbed and utilized by the human body, but also has higher bioavailability, and is mild in nature and has little irritation to the gastrointestinal tract. This is because the present invention uses a specific calcium accelerator and calcium citrate as the main ingredients to promote calcium absorption, while improving the calcium supplement efficiency, avoiding gastrointestinal discomfort symptoms and preventing constipation.

[0086] The above embodiments are merely descriptions for the purpose of clearly illustrating the present invention, and are not limitations on the implementation methods. For technicians in the relevant field, other different forms of changes or modifications can be made based on the above descriptions. It is not necessary and impossible to list all the implementation methods here, and the obvious changes or modifications derived therefrom are still within the scope of protection of the present invention.

Claims

1. A compound preparation of calcium citrate casein phosphopeptide calcium tablets, comprising the following components in weight percentage: 90-96% calcium citrate particles, 0.68-1.84% casein phosphopeptide, 0.08-0.16% vitamin D3 powder, 0.7-1.5% vitamin K2 powder, 0.5-1.5% sodium carboxymethyl starch, 0.6-1.0% magnesium stearate; 2-4% coating premix.

2. The compound preparation of calcium citrate casein phosphopeptide calcium tablets according to claim 1, characterized in that: The calcium citrate particles contain the following components in weight percentage: 84-90% calcium citrate, 6-11% maltodextrin, and 4-5% edible corn starch.

3. The compound preparation of calcium citrate casein phosphopeptide calcium tablets according to claim 1, characterized in that: The mesh number of the calcium citrate is 100-1500 meshes.

4. The method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets according to claim 1, characterized in that: The following steps are involved: Step 1: calcium citrate wet granulation; Step 2: Mixing; Step 3: pressing into tablets; Step 4: Coating.

5. The method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets according to claim 4, characterized in that: In the step 1, calcium citrate and maltodextrin are mixed, and corn starch and an appropriate amount of water are used to prepare a slurry with a concentration of 8-15%, and the mixture is heated to fully dissolve into starch slurry, and the mixture is put into a wet granulator and stirred for 1-10 minutes to mix well.

6. The method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets according to claim 4, characterized in that: In the step 2, the calcium citrate particles are fully mixed with other components except the coating premix.

7. The method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets according to claim 4, characterized in that: In the step 3, the mixture is pressed into tablets using a high-speed rotary tablet press.

8. The method for preparing a compound preparation of calcium citrate casein phosphopeptide calcium tablets according to claim 4, characterized in that: In the step 4, a coating premix solution is prepared with a concentration of 10-20% to coat the tablets prepared in the step 3.

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