CN115804759B - Granule containing coenzyme Q10 and calcium - Google Patents
Granule containing coenzyme Q10 and calcium Download PDFInfo
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- CN115804759B CN115804759B CN202211586379.XA CN202211586379A CN115804759B CN 115804759 B CN115804759 B CN 115804759B CN 202211586379 A CN202211586379 A CN 202211586379A CN 115804759 B CN115804759 B CN 115804759B
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- 239000008187 granular material Substances 0.000 title claims abstract description 63
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 title claims abstract description 48
- 235000017471 coenzyme Q10 Nutrition 0.000 title claims abstract description 47
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 229940110767 coenzyme Q10 Drugs 0.000 title claims abstract description 35
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 229910052791 calcium Inorganic materials 0.000 title claims abstract description 17
- 239000011575 calcium Substances 0.000 title claims abstract description 17
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 117
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 89
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 44
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims abstract description 31
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000001630 malic acid Substances 0.000 claims abstract description 31
- 235000011090 malic acid Nutrition 0.000 claims abstract description 31
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 22
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- UUGXJSBPSRROMU-UHFFFAOYSA-N 2,3-dimethoxy-5-methyl-2-<(all-E)-3',7',11',15',19',23',27',31',35'-nonamethylhexatriaconta-2',6',10',14',18',22',26',30',34',nonaenyl>cyclohexa-2,5-dien-1,4-dion Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O UUGXJSBPSRROMU-UHFFFAOYSA-N 0.000 description 2
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- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides granules containing coenzyme Q10 and calcium, which comprise 750 parts of calcium carbonate, 50-250 parts of coenzyme Q10150, 60-100 parts of citric acid, 60-100 parts of malic acid, 30-40 parts of microcrystalline cellulose, 20-40 parts of flavoring agent and 3-5 parts of magnesium stearate, wherein the coenzyme Q10 is microcapsule powder of the coenzyme Q10; the granule provided by the invention can be directly taken orally without brewing, and is convenient to take, good in compliance and good in taste.
Description
Technical Field
The invention relates to a granule composition, belongs to the field of medicine/food preparations, and in particular relates to granules containing coenzyme Q10 and calcium carbonate, which are taken by chewing.
Background
Coenzyme Q10 (Coenzyme Q, coQ 10) is also called ubiquinone, is a fat-soluble retinoid compound in various organism cells, can activate nutrition of human cells and cell energy, and has the functions of improving human immunity, resisting oxidation, delaying aging, enhancing human vigor and the like. The medicine is widely used for treating cardiovascular system diseases and is widely used for providing nutritional foods such as immunity, anti-aging and the like at home and abroad. In addition, the composition is also used as an auxiliary treatment drug for diseases such as diabetes, alzheimer disease, cancer and the like. However, coQ10 has limited application dosage forms due to its hydrophobic, easily oxidized, and unstable properties to light and heat, and is mainly used in soft capsules. Although microencapsulated CoQ10 materials have been developed to solve the problem of hydrophobicity and significantly improve the stability, they are also relatively sensitive to light, heat and moisture.
In recent years, coQ10 has been studied to reduce the occurrence of osteoporosis by regulating bone metabolism (by promoting bone formation by bone cells, inhibiting bone resorption by osteoclasts, inhibiting oxidative stress and cell aging, etc., to prevent bone loss). However, no related products, especially compositions for preventing and treating osteoporosis, such as CoQ10 and calcium, which have higher compliance and higher comprehensiveness, are known. Calcium supplement is a main measure for preventing and treating osteoporosis, and calcium tablets (including chewable tablets) are used in the market, and soft/hard capsules and a small amount of granules are also used. Because the gap of the daily calcium demand of the human body is large and the calcium content of the calcium source is limited, the tablet/granule weight of the calcium tablet/capsule is large, the foreign body sensation after swallowing is obvious at 1-2g, and the compliance is poor; although the chewing tablet has no problem of discomfort after swallowing, the tablet has certain hardness due to the requirement of friability, and is laborious in initial chewing, especially for the elderly or people with dental diseases, and the compliance is also poor. For such longer-lived nutrients, poor compliance would undoubtedly be a major compromise in their target effect. In addition, the primary calcium supplement is also unilateral and passive for preventing and treating osteoporosis, but has adverse effects on medicines for resisting bone resorption (such as biphosphate) and promoting bone formation (such as teriparatide), and is not suitable for people with light symptoms and risks.
Therefore, the nutritional composition which can not only fundamentally inhibit the occurrence of osteoporosis, but also increase bone density to relieve the osteoporosis, is convenient to take, has good compliance and high safety, and is expected by patients with the osteoporosis or high risk groups.
Disclosure of Invention
The invention aims to solve the technical problem of providing a dosage form which is more beneficial to long-term eating and contains coenzyme Q10 and calcium, in particular to a granule which is taken by chewing.
In order to solve the problems, the invention provides granules containing coenzyme Q10 and calcium, which comprise, by weight, 750 parts of calcium carbonate, 150-250 parts of coenzyme Q10, 60-100 parts of citric acid, 60-100 parts of malic acid, 30-40 parts of microcrystalline cellulose, 20-40 parts of flavoring agents and 3-5 parts of magnesium stearate, wherein the coenzyme Q10 is microcapsule powder. The coenzyme Q10 microcapsule powder is also called coenzyme Q10 powder, the content of coenzyme Q10 is 9-11%, usually about 10%, and the coenzyme Q10 microcapsule powder is easy to disperse in 15 ℃ cold water, and 90% of the coenzyme Q10 microcapsule powder can pass through a 60-mesh sieve. The weight parts of the coenzyme Q10 can be regulated according to the content of the microcapsule powder raw materials, and can also be prepared into different specifications such as 15mg, 25mg, 30mg, 50mg (calculated by pure coenzyme Q10) and the like for each eating. The adjustment of the coenzyme Q10 parts by weight here does not significantly affect the amounts of the other components.
The corrigent is sweetener or combination of sweetener and essence, the choice of corrigent can be determined according to audience, and the corrigent can be made into various tastes for people to choose. In addition, the granule of the invention can be added with a proper amount of coloring agent to make the granule light green, light yellow and the like so as to increase the eating desire or distinguish different tastes.
Calcium carbonate has the advantage of high calcium content, which is the most important source of calcium in calcium supplement products, but has the disadvantage of being insoluble in water, so that the administration mode is mainly swallowing and small chewing. In order to meet the basic requirement of supplementing 600mg of calcium (1500 mg of calcium carbonate) every day, even if the tablet/capsule taken for 2 times every day reaches 1-2g, the compliance of taking is poor. In addition, the calcium carbonate form of the food reacts with gastric acid to release carbon dioxide, which causes discomfort such as hiccups and flatulence. Although there is also a technical disclosure of preparing effervescent granules by compounding calcium carbonate with citric acid and malic acid, the effervescent granules are sufficient to react by brewing with warm water, and therefore are not suitable for compositions containing coenzyme Q10 which is sensitive to temperature. Accordingly, the present inventors have made extensive studies to prepare chewable granules of calcium carbonate and coenzyme Q10. The granule does not need to be chewed and chewed as a chewable tablet, does not generate foreign body sensation, does not need to be taken by drinking water, can be taken at any time even when going out, and is very convenient and comfortable. More importantly, in the chewing process, citric acid and malic acid in the ingredients can react with part of calcium carbonate to release a certain amount of carbon dioxide, so that the phenomena of hiccups/flatulence can be relieved, and the absorption effect of calcium can be improved.
In order to further promote the absorption of calcium, the granules of the invention also contain vitamin D3, preferably more stable vitamin D3 inclusion compound, and the dosage is 60-100 International Units (IU). 60-100IU of the vitamin D3 clathrate is about 0.6-1mg based on 10 ten thousand IU/g of the vitamin D3 clathrate.
The granule is prepared by the following steps:
1) Mixing 90% of citric acid and malic acid, mixing with calcium carbonate, adding 83-88% ethanol to make soft material, granulating with 20 mesh sieve, and drying at 50-60deg.C to obtain granule 1;
2) Mixing granule 1 with the rest citric acid and other materials, and dry granulating.
Citric acid and malic acid are both auxiliary materials with obvious sour taste, how to react calcium carbonate as much as possible while ensuring the taste, and the stability of coenzyme Q10 is not destroyed, which is a brand new problem encountered by the invention, and the prior art has no disclosure or suggestion. The inventor obtains the formula and the preparation process of the granule through a large number of experiments. When the weight ratio of the calcium carbonate to the citric acid to the malic acid is (3.75-6.25): 1, a small amount of sweetener is added, the taste is good, the phenomenon of peracid and flatulence/hiccup is avoided, and the phenomenon of direct eating of the equivalent amount of calcium carbonate (without citric acid and malic acid) is also reduced; the two acids are uniformly mixed and then are uniformly mixed with the calcium carbonate to be granulated separately, and then are mixed with other components to be granulated in a dry method, so that the acid-base reaction sufficiency during chewing is further improved, the taste impact of sour taste is reduced, and the damage of coenzyme Q10 in water and heat is avoided. Meanwhile, a small amount (such as 10%) of citric acid is left to be placed in the second step of dry granulation, so that the granules can feel light sour taste as soon as possible when being just imported to stimulate taste buds to secrete saliva, acid-base reaction and swallowing are facilitated, meanwhile, the acidity after chewing is also laid, and the granules are more acceptable to users. In a preferred embodiment, the ratio of citric acid to malic acid used in step 1) is 1:1, which is beneficial for its reaction with calcium carbonate to be sufficient. When the chewing gum is chewed, the calcium carbonate reacts with the citric acid and the malic acid to generate a small amount of bubbles, and the chewing gum combines the sweet and sour fruit flavor, has pleasant taste, supplements nutrient substances while enjoying delicious taste, is beneficial to people to continuously eat so as to realize the purpose of preventing and treating osteoporosis, and further improves the quality of life.
Because the particle size of the coenzyme Q10 microcapsule powder is small (about 60 meshes), the particle 1 prepared by the preparation method is not suitable to be too large and too hard, and the inventor also screens the adhesive for preparing the soft material, so that the effect of adding the ethanol solution with specific concentration into the adhesive with different dosage or variety is more ideal.
The granules obtained in step 2) of the above preparation method can be preferably 70-85% sieved by a 10-mesh sieve, and the fine particles sieved by a 40-mesh sieve are not more than 5%, so as to achieve good taste and create chewing time to promote the reaction of calcium carbonate and diacid. The dry granulation technique is a granulation method commonly used in the art, and specific steps are not repeated.
In another preferred embodiment, the granule is prepared from the following raw materials, by weight, 750 parts of calcium carbonate, 250 parts of coenzyme Q, 90 parts of citric acid, 81 parts of malic acid, 30 parts of microcrystalline cellulose, 25 parts of aspartame, 15 parts of pineapple essence, 3 parts of magnesium stearate and 100 international units of vitamin D.
The invention provides granules containing coenzyme Q10 and calcium carbonate for the first time, which not only fills up the market blank of nutritional products for comprehensively preventing and treating osteoporosis, but also avoids the limitation of swallowing foreign body sensation and chewing pressure on the people in need of the people in the form of chewing granules, is convenient to take, has good taste, is beneficial to the eaters to insist on supplementing nutrients, and achieves the purpose of relieving or preventing osteoporosis.
The inventors further verified the technical effects of the present invention through experiments.
Reiterate again: the following experiments are only exemplary of numerous experiments in the development process of the present invention, and not all experiments performed by the inventor for the present invention are covered and exhausted, only to illustrate the influence of different formulations on the granular mouthfeel and the degree of acid-base reaction.
Experiment: influence of different dosages of citric acid and malic acid and processes on mouthfeel of particles
200 Parts of granules are prepared according to the following table formulas and corresponding processes, wherein each formula is sequentially taken by 30 volunteers (40-70 years old, 70% of which are women) every other day, and the mouth feel and the hiccup and flatulence condition within 2 hours are fed back. The results are detailed in the following table:
the process of the prescription 1-3 is as follows: mixing the raw materials, and directly granulating by a dry method.
The process of the prescription 4-6 is as follows: mixing calcium carbonate with citric acid and malic acid, granulating with 85% ethanol by wet method, mixing with other raw materials, granulating by dry method, and sieving 80% with 10 mesh sieve.
The process of the prescription 7 is as follows: mixing 90% of citric acid and malic acid, mixing with calcium carbonate, granulating with 85% of ethanol by wet method, mixing with the rest of citric acid and other raw materials, granulating by dry method, sieving 75% with 10 mesh sieve, and sieving with 40 mesh sieve to obtain granule not higher than 5%.
From the experimental results, the addition of a proper amount of citric acid and malic acid can relieve the hiccup/flatulence phenomenon after taking the same amount of calcium carbonate, and particularly, the relieving effect is more obvious after the three raw materials are singly granulated. Although unreacted calcium carbonate still produces a gritty feel, conventional calcium carbonate chewable tablets have improved over the same dosage. The dosage of citric acid and malic acid in the formula 3 is doubled compared with that in the formula 2, but the hiccup/flatulence phenomenon is consistent in number, and the analysis reasons are probably that the particles are scattered into the formula 3 and overacid after entering the mouth, so that volunteers swallow the particles quickly, and the reaction time is too short.
The granule disclosed by the invention does not produce swallowing foreign body sensation, does not need larger biting force, is more convenient and comfortable to take than the existing preparation form, and meanwhile relieves stomach discomfort after calcium carbonate is taken to a certain extent, so that the compliance of the granule is greatly improved.
Detailed Description
Example 1
Coenzyme Q10 calcium carbonate particles (1000 bags)
750G of calcium carbonate, 250g of coenzyme Q, 60g of citric acid, 80g of malic acid, 40g of microcrystalline cellulose, 20g of aspartame and 5g of magnesium stearate.
The process comprises the following steps: 1. mixing citric acid and malic acid, mixing with calcium carbonate, adding 83% ethanol to obtain soft material, sieving with 20 mesh sieve, granulating, and drying at 60deg.C to obtain granule 1.
2. Mixing granule 1 with other materials, dry granulating, sieving with 10 mesh sieve with 70% granule of 5% of 40 mesh sieve, and packaging.
Example 2
Coenzyme Q10 calcium carbonate particles (1000 bags)
750G of calcium carbonate, 150g of coenzyme Q, 100g of citric acid, 60g of malic acid, 30g of microcrystalline cellulose, 20g of aspartame and 3g of magnesium stearate.
The process comprises the following steps: 1. mixing 90% of citric acid and malic acid, mixing with calcium carbonate, adding 85% ethanol to make soft mass, sieving with 20 mesh sieve, granulating, and drying at 50deg.C to obtain granule 1.
2. Mixing granule 1 with the rest citric acid and other materials, dry granulating, sieving with 10 mesh sieve to give 80% granule with 4% fine granule of 40 mesh sieve, and packaging.
Example 3
Coenzyme Q10 calcium carbonate particles (1000 bags)
750G of calcium carbonate, 200g of coenzyme Q, 100g of citric acid, 100g of malic acid, 35g of microcrystalline cellulose, 25g of aspartame, 15g of orange essence and 4g of magnesium stearate.
The process comprises the following steps: 1. mixing 95% citric acid and malic acid, mixing with calcium carbonate, adding 88% ethanol to make soft mass, sieving with 20 mesh sieve, granulating, and drying at 55deg.C to obtain granule 1.
2. Mixing granule 1 with the rest citric acid and other materials, dry granulating, sieving with 10 mesh sieve to obtain granule with 75% of granule size of 3% of granule passing through 40 mesh sieve, and packaging.
Example 4
Coenzyme Q10 calcium carbonate particles (1000 bags)
750G of calcium carbonate, 250g of coenzyme Q, 80g of citric acid, 90g of malic acid, 35g of microcrystalline cellulose, 25g of aspartame, 4g of magnesium stearate and 2g of sunset yellow (pigment).
The process comprises the following steps: 1. mixing citric acid with 85% of formula amount with malic acid and sunset yellow, mixing with calcium carbonate, adding 85% ethanol to obtain soft material, sieving with 20 mesh sieve, granulating, and drying at 60deg.C to obtain granule 1.
2. Mixing granule 1 with the rest citric acid and other materials, dry granulating, sieving with 10 mesh sieve to give granule of 85% with granule of 4% of 40 mesh sieve, and packaging.
Example 5
Coenzyme Q10 calcium carbonate particles (1000 bags)
750G of calcium carbonate, 250g of coenzyme Q, 90g of citric acid, 81g of malic acid, 30g of microcrystalline cellulose, 25g of aspartame, 15g of pineapple essence, 3g of magnesium stearate and 1mg of vitamin D3 (10 ten thousand IU/g inclusion compound).
The process comprises the following steps: 1. mixing 90% of citric acid and malic acid, mixing with calcium carbonate, adding 85% ethanol to make soft mass, sieving with 20 mesh sieve, granulating, and drying at 60deg.C to obtain granule 1.
2. Mixing granule 1 with the rest citric acid and other materials, dry granulating, sieving with 10 mesh sieve to obtain granule with 80% of granule size of 3% of 40 mesh sieve, and packaging.
Example 6
Coenzyme Q10 calcium carbonate particles (1000 bags)
750G of calcium carbonate, 150g of coenzyme Q, 60g of citric acid, 60g of malic acid, 40g of microcrystalline cellulose, 20g of aspartame, 10g of pineapple essence, 4g of magnesium stearate and 0.6mg of vitamin D3 (10 ten thousand IU/g inclusion compound).
The process comprises the following steps: same as in example 5.
The foregoing is merely a partial embodiment of the present invention, and is intended to further illustrate the present invention, not to limit the scope of the present invention. Modifications and variations of the above-described embodiments, which do not depart from the scope and spirit of the invention, are intended to be included within the scope of the invention as claimed.
Claims (8)
1. The chewing granule containing coenzyme Q10 and calcium is characterized by comprising the following raw materials, by weight, 750 parts of calcium carbonate, 150-250 parts of coenzyme Q10, 60-100 parts of citric acid, 60-100 parts of malic acid, 30-40 parts of microcrystalline cellulose, 20-40 parts of flavoring agent and 3-5 parts of magnesium stearate, wherein the coenzyme Q10 is microcapsule powder, and the granule is prepared by the following steps:
1) Mixing malic acid with 90% of citric acid, mixing with calcium carbonate, adding 83-88% ethanol to obtain soft material, granulating with 20 mesh sieve, and drying at 50-60deg.C to obtain granule 1;
2) Mixing granule 1 with the rest citric acid and other materials, and dry granulating.
2. The granule according to claim 1, wherein the coenzyme Q10 content of the coenzyme Q10 microcapsule powder is 9-11%.
3. The granule of claim 1, wherein the flavoring agent is a sweetener or a combination of a sweetener and a flavoring agent.
4. The granule of claim 1, further comprising vitamin D 3 in an amount of 60 to 100 international units.
5. The granule of claim 4, wherein the vitamin D 3 is an inclusion compound.
6. The granule of claim 1, wherein the ratio of citric acid to malic acid in step 1) is 1:1.
7. The granule as claimed in claim 1, wherein 70 to 85% of the granule obtained in said step 2) can pass through a 10-mesh sieve and not more than 5% of the granule passes through a 40-mesh sieve.
8. The granule as claimed in claim 1, wherein the granule is prepared from the following raw materials, by weight, 750 parts of calcium carbonate, 250 parts of coenzyme Q, 90 parts of citric acid, 81 parts of malic acid, 30 parts of microcrystalline cellulose, 25 parts of aspartame, 15 parts of pineapple essence, 3 parts of magnesium stearate, and 3 international units of vitamin D.
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