CN105213423A - A kind of calcium carbonate D 3sheet and preparation method thereof - Google Patents
A kind of calcium carbonate D 3sheet and preparation method thereof Download PDFInfo
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- CN105213423A CN105213423A CN201510724604.5A CN201510724604A CN105213423A CN 105213423 A CN105213423 A CN 105213423A CN 201510724604 A CN201510724604 A CN 201510724604A CN 105213423 A CN105213423 A CN 105213423A
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Abstract
The invention provides a kind of calcium carbonate D
3sheet and preparation method thereof, this calcium carbonate D
3sheet comprises following component by weight: Paris white 1250g, vitamin d3 powder 2g, disintegrating agent 6.5g, lubricant 1g and other medically acceptable adjuvant 170g, described medically acceptable adjuvant contains microcrystalline Cellulose 102, and the weight content of microcrystalline Cellulose 102 is up to 4%.In the present invention, final obtained calcium carbonate D
3about 1.4g in the sheet of sheet, the calcium carbonate D heavy relative to gram sheet of 1.8 on the market
3sheet can reduce sheet and weigh and volume, is convenient for carrying and swallows, and calcium carbonate D
3every active constituent content in sheet is even, steady quality; Meanwhile, this preparation method is simple, workable, is conducive to industrial volume production.
Description
Technical field
The invention belongs to pharmaceutical technology sectors, particularly a kind of calcium carbonate D improving osteoporosis
3sheet and preparation technology.
Background technology
The statistics of World Health Organization (WHO) shows, the sickness rate of current osteoporosis leaps to the 7th in world's common frdquently encountered disease, patient populations is more than 200,000,000 people in the world, will there is osteoporotic fracture in the whole world old women of 1/2 and the elderly men of 1/3, wherein only just there are more than 7,500 ten thousand people in the U.S., West Europe and Japan.Along with the formation of China's aging society, predict the year two thousand fifty, sufferers of osteoporosis face, comprise bone amount and reduce, will 2.12 × 10 be reached
8example, accounts for 13.2% of total population.Osteoporosis will become serious public health problem, especially postclimacteric women, and because of hypo-ovaria, unit volume osseous tissue amount reduces to be accelerated, and the sickness rate of its osteoporosis and fracture complication is higher.
Osteoporosis is because human body bone absorbs and unbalance one group of the produced disease of New bone formation, is divided into senile osteoporosis and postmenopausal osteoporosis two class according to the Etiological that it produces.As control principle, the former multiplex medicine that can promote New bone formation, the latter is then based on bone absorption inhibitor, and in two osteoid osteoporosis, prevention is all acknowledged as most important, because once there is osteoporosis, excellent sclerotin is just again difficult to recover as before, once generation osteoporotic fracture, patients ' life quality declines, and occurs various complication, can disable, lethal, therefore, the prevention of osteoporosis is more more real and important than treatment.
Calcium is the important nutrient of sufferers of osteoporosis face, and being New bone formation phase necessary element in whole vital stage bone remoulding process, is also the macroelement that in human body mineral, content is maximum, and in body, 99% of calcium total amount is stored in skeleton.The basic measure of prevention of osteoporosis has adjustment life style and supplementary bone health essential drugs, it is 1000mg that postmenopausal women and old people's calcium every day take in recommended amounts, the current display of the Dietary survey for China old people, from diet, obtain that calcium only has recommended dose average every day 2/5, therefore this crowd should notice that average every day should supplement calcium preparation, calcium preparation supplement should follow principle of individuation, and close observation patient calculus a situation arises and adverse cardiac events.
Calcium carbonate is one of traditional calcium complement agent of China, its advantage is that calcium content is high, advantages of good calcium supplying effect, and after the formation that can participate in skeleton at the calcium ion of human body release after oral and fracture, osseous tissue builds and muscle contraction, neurotransmission, clotting mechanism reduce the permeability etc. of blood capillary again.
Vitamin D
3have multiple action, the absorption of calcium can be promoted, to bone health, maintain muscular strength, improve body steadiness, to reduce risk of bone fracture useful.Adult's vitamin D
3recommended dose is 200IU/d, old people's for want of sunshine and absorption and malabsorption, therefore recommended dose is slightly large.Vitamin D
3when being used for the treatment of osteoporosis, dosage is 800 ~ 1200IU/d.International osteoporosis foundation suggestion old people serum 25 (OH) VitD level >=30ng/ml (75mol/L), falls and risk of bone fracture to reduce, should note individual variation and safety during clinical practice, periodic detection blood calcium or urine calcium.
China issued patent CN102908359B discloses " a kind of calcium carbonate vitamin D
3composition of granule and preparation method thereof ", its drug content uniformity and release are all better, but granule needs with aqueous dispersion before taking, more loaded down with trivial details, and packaging volume is large, carry be not as convenient as tablet.China issued patent CN103301149B discloses a kind of pharmaceutical preparation increasing bone density, improve bone density, and its composition comprises the composition such as D-Glucosamine Hydrochloride and chondroitin sulfate.Chinese invention patent application CN102716149A discloses " a kind of calcium carbonate D
3effervescent tablet and preparation method thereof ", all exist and take the defects such as inconvenient.
At present, the calcium carbonate D on market
3sheet volume is comparatively large, and every sheet weight is about 1.8g, is not easy to take, and in order to overcome above-mentioned defect, it is heavy to 1.4g that the prescription composition that the present invention relates to can alleviate sheet, do not lose effective ingredient simultaneously.Secondly, due to vitamin D
3content is few, and be difficult to mix homogeneously, the Gaierqi D (vitamin D3 and calcium carbonate) equal size uniformity of having gone on the market is all undesirable, and the preparation process in the present invention can make vitamin D
3uniformity of dosage units improve.
In view of this, be necessary calcium carbonate D of the prior art
3sheet and preparation method thereof is improved, to solve the problem.
Summary of the invention
The object of the invention is to open a kind of calcium carbonate D
3sheet and calcium carbonate D thereof
3the preparation method of sheet, in order to reduce calcium carbonate D
3do not lose effective ingredient while the weight of sheet, guarantee vitamin D simultaneously
3content be uniformly distributed in calcium carbonate D
3in sheet.
For realizing above-mentioned first goal of the invention, the invention provides a kind of calcium carbonate D
3sheet, comprises following component by weight:
Paris white 1250g, vitamin D
3powder 2g, disintegrating agent 6.5g, lubricant 1g and other medically acceptable adjuvant 170g, described medically acceptable adjuvant contains microcrystalline Cellulose 102, and the weight content of microcrystalline Cellulose 102 is up to 4%.
In certain embodiments, medically acceptable adjuvant comprises binding agent, wetting agent and filler.
In certain embodiments, binding agent is hypromellose, polyvidone, starch, pregelatinized Starch, dextrin, microcrystalline Cellulose, methylcellulose or ethyl cellulose.
In certain embodiments, wetting agent is selected from ethanol or purified water.
In certain embodiments, filler is selected from starch, dextrin, lactose, glucose, pregelatinized Starch or mannitol.
In certain embodiments, disintegrating agent is polyvinylpolypyrrolidone, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose or hydroxypropyl starch.
In certain embodiments, lubricant is magnesium stearate, stearic acid or micropowder silica gel.
For realizing above-mentioned second goal of the invention, the invention also discloses a kind of calcium carbonate D
3the preparation method of sheet, comprises the following steps:
Step 1): Paris white adds wetting agent after mixing homogeneously with medically acceptable adjuvant and obtains soft material;
Step 2): soft material is crossed 30 eye mesh screen pelletizes and is obtained wet granular;
Step 3): under wet granular is placed in 60 DEG C ~ 70 DEG C conditions, dried obtains the dry granule that moisture content is 1% ~ 2%;
Step 4): vitamin D
3powder is pulverized and is crossed 100 eye mesh screens;
Step 5): by step 3) in dry granule with cross the vitamin D of 100 eye mesh screens
3powder, disintegrating agent, lubricant and medically acceptable adjuvant mix homogeneously, tabletting.
Preferably, this step 3) in the baking temperature of wet granular be 60 DEG C.
Preferably, the particle diameter D of microcrystalline Cellulose 102
15be 45 ± 2 μm, D
85be 60 ± 1.5 μm, porosity (5.0 ± 0.4) × 10
-5cm
3/ g.
Compared with prior art, the invention has the beneficial effects as follows: in the present invention, final obtained calcium carbonate D
3about 1.4g in the sheet of sheet, the calcium carbonate D heavy relative to gram sheet of 1.8 on the market
3sheet can reduce sheet and weigh and volume, is convenient for carrying and swallows, and calcium carbonate D
3every active constituent content in sheet is even, steady quality; Meanwhile, this preparation method is simple, workable, is conducive to industrial volume production.
Accompanying drawing explanation
Fig. 1 is calcium carbonate D of the present invention
3the flow chart of the preparation method of sheet;
Fig. 2 is vitamin D
3canonical plotting;
Fig. 3 is vitamin D
3method applicability chromatogram.
Detailed description of the invention
Below in conjunction with each embodiment shown in the drawings, the present invention is described in detail; but should be noted that; these embodiments are not limitation of the present invention; those of ordinary skill in the art are according to these embodiment institute work energy, method or structural equivalent transformations or substitute, and all belong within protection scope of the present invention.Unless had specified otherwise in description, the component in each embodiment in the present invention, raw material all adopt analytical pure rank.In addition, " g " in each embodiment is unit of weight " gram "; " h " is unit of time " hour "; " ml " is volume unit " milliliter "; " room temperature " is 23 DEG C.
embodiment 1:
Prescription 1 (specification 500mg/200IU)
Preparation method: Paris white mixes with MCC, add 100ml purified water and obtain soft material, soft material is crossed 30 eye mesh screens and is obtained wet granular.Wet granular is placed in drying baker, and adjusts the temperature to 60 DEG C of dried, with the dry granule making wet granular moisture content be reduced to 1% ~ 2%, and use 40 eye mesh screen granulate.Vitamin D
3powder crosses 100 eye mesh screens after pulverizing.By calcium carbonate dry granule and vitamin D
3powder, microcrystalline Cellulose 102, cross-linking sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, tabletting, to obtain final product.Wherein, microcrystalline Cellulose 102, cross-linking sodium carboxymethyl cellulose and magnesium stearate all cross 100 eye mesh screens.Preferably, in embodiment 1, the particle diameter D of this microcrystalline Cellulose 102
15be 45 ± 2 μm, D
85be 60 ± 1.5 μm, porosity (5.0 ± 0.4) × 10
-5cm
3/ g.
embodiment 2:
Prescription 2 (specification 500mg/200IU)
Preparation method: Paris white mixes with pregelatinized Starch, adds 120ml purified water and obtains soft material.Soft material is crossed 30 eye mesh screens to granulate to obtain wet granular.Wet granular is placed in drying baker, and adjusts the temperature to 65 DEG C of moisture be dried in dry granule and be reduced to 1% ~ 2%, dry granule is crossed 40 eye mesh screen granulate.Vitamin D
3powder crosses 100 eye mesh screens after pulverizing.Calcium carbonate dry granule and vitamin D
3powder, microcrystalline Cellulose 102, cross-linking sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, tabletting, to obtain final product.Wherein, microcrystalline Cellulose 102, cross-linking sodium carboxymethyl cellulose, magnesium stearate all cross 100 eye mesh screens.
embodiment 3:
Prescription 3 (specification 500mg/200IU)
Preparation method: Paris white mixes with polyvidone, adds the obtained soft material of 100ml purified water mixing.Soft material is crossed the obtained wet granular of 30 order mesh screens granulation.Wet granular is placed in drying baker, and adjusts the temperature to 70 DEG C of moisture be dried in dry granule and be reduced to 1% ~ 2%, 40 mesh sieve granulate; Vitamin D
3powder crosses 100 eye mesh screens after pulverizing.By calcium carbonate dry granule and vitamin D
3powder, microcrystalline Cellulose 102, cross-linking sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, tabletting, to obtain final product.Wherein, microcrystalline Cellulose 102, cross-linking sodium carboxymethyl cellulose, magnesium stearate all cross 100 eye mesh screens.
embodiment 4:
Prescription 4 (specification 500mg/200IU)
Preparation method: Paris white mixes with whole pregelatinized Starch, adds 110ml purified water and obtains soft material.Soft material is crossed 30 eye mesh screens to granulate to obtain wet granular.Wet granular is positioned in drying baker, adjusts the temperature to 60 DEG C of dryings, be reduced to 1% ~ 2% to make wet granular moisture content.Dry granule crosses 40 eye mesh screen granulate.Vitamin D
3powder crosses 100 eye mesh screens after pulverizing.By calcium carbonate dry granule and vitamin D
3powder, microcrystalline Cellulose 102, low-substituted hydroxypropyl cellulose, micropowder silica gel mix homogeneously, tabletting, to obtain final product.Wherein, microcrystalline Cellulose 102, low-substituted hydroxypropyl cellulose, micropowder silica gel all cross 100 eye mesh screens.
embodiment 5:
Prescription 5 (specification 500mg/200IU)
Preparation method: Paris white mixes with whole pregelatinized Starch, adds 100ml ethanol (concentration: 75%) obtained soft material.Soft material is crossed 30 order mesh screens to granulate to obtain wet granular.Be positioned over by wet granular in drying baker, adjust the temperature to 60 DEG C and be reduced to 1% ~ 2% to make wet granular moisture content, dry granule crosses 40 eye mesh screen granulate.Vitamin D
3powder crosses 100 eye mesh screens after pulverizing.By calcium carbonate dry granule and vitamin D
3powder, microcrystalline Cellulose 102, carboxymethyl starch sodium, magnesium stearate mix homogeneously, tabletting, to obtain final product.Wherein, microcrystalline Cellulose 102, carboxymethyl starch sodium, magnesium stearate all cross 100 eye mesh screens.
Result of the test:
1, calcium carbonate granule mobility and draw moist
The mobility of different prescription calcium carbonate granule and to draw moist result as shown in table 1.
| Embodiment | Moisture/% | Angle of repose θ | Degree of compression C% | Percentage weight increase % |
| 1 | 1.30 | 35.77° | 22.05 | 0.40 |
| 2 | 0.90 | 28.54° | 18.71 | 0.37 |
| 3 | 1.30 | 40.88° | 28.16 | 0.45 |
| 4 | 1.10 | 15.57° | 12.05 | 0.77 |
| 5 | 1.15 | 16.02° | 11.87 | 0.72 |
Table 1: calcium carbonate D in embodiment 1 to embodiment 5
3the mobility of the granule of sheet and draw moist result
Due to, angle of repose, θ was less, and frictional force is less, and mobility is better.During general θ <40 °, need of production can be met; θ <30 ° illustrates that mobility is fine.Degree of compression C% reacts coherency, the doughy state of powder body.During C<20%, mobility is better, and when C increases, mobility is deteriorated.Therefore embodiment 2 is better than the mobility of particle in embodiment 1, and namely pregelatinized Starch and Paris white are granulated and more can be met Production requirement.Embodiment 4 is better with the mobility of the calcium carbonate granule in embodiment 5, obtained calcium carbonate D
3sheet is unilateral smooth.
According to Chinese Pharmacopoeia (2015 editions) four general rules 9103 " medicine draws moist test direction principle ", draw wet weightening finish and be less than 2% but be not less than 0.2% moist for slightly to draw, therefore all prescriptions all slightly draw moist.
2, Determination of Content Uniformity
(1) test method: be the chromatographic column of filler with silica gel, with the hexane solution containing 0.45% (V/V) isopropyl alcohol for mobile phase A, the hexane solution of 20% (V/V) isopropyl alcohol is Mobile phase B, and according to the form below carries out gradient elution:
| Time (minute) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 100 | 0 |
| 25 | 100 | 0 |
| 26 | 0 | 100 |
| 30 | 0 | 100 |
| 31 | 100 | 0 |
| 37 | 100 | 0 |
Determined wavelength is 265nm, and flow velocity is 1.0ml/min, and the concrete reference standard WS1-(X-002) of detection method-2008I-2012 carries out, thus obtains vitamin D3 method applicability chromatogram as shown in Figure 3.
(2) result of the test:
Get vitamin D
3certain density solution prepared by reference substance, production standard curve, and peak area is mapped to concentration, and as shown in following table 2 and Fig. 2, result of the test shows that the method is reliable and stable, vitamin D
3concentration good in 0.35IU/ml ~ 217.6IU/ml scope internal linear relation.Fig. 2 for by as the data in following table 2 the vitamin D that formed
3canonical plotting.
| Chromatogram peak area peak area/A | VD3 reference substance concentration/IU/ml |
| 0.00 | 0.06963 |
| 1.01 | 0.34816 |
| 5.20 | 1.74080 |
| 25.85 | 8.70400 |
| 127.60 | 43.5200 |
| 639.05 | 217.600 |
Table 2: vitamin D
3standard curve data
As shown in Figure 3, shown by system suitability, vitamin D
3tailing factor be 1.1 (being not more than 2.0), and vitamin D
3the relative standard deviation of peak area was 1.4% (being not more than 3.0%), vitamin D
3with provitamin D
3separating degree be 15.1 (being not less than 3.0), system suitability is qualified.
According in EP8.0 to the regulation of tablet content cloud test and computational methods, T is actual inventory; The constant that k is sampling amount when being 10, k=2.4.Because the production inventory of Gaierqi D (vitamin D3 and calcium carbonate) is unknown, therefore can not calculate |
| the concrete numerical value of+kS, but the mixability that can be compared two kinds of techniques by standard deviation, with the vitamin D in Gaierqi D (vitamin D3 and calcium carbonate)
3the standard deviation of content is compared, and the standard deviation of the embodiment 1 ~ 5 of present invention process is far smaller than Gaierqi D (vitamin D3 and calcium carbonate).
Specify in EP8.0 |
| the numerical value of+kS should be less than 15 in no special situation, and the measurement result of the embodiment 1 ~ 5 of present invention process all conforms with the regulations, and therefore this technique can make vitamin D
3content mix homogeneously, specifically please refer to shown in table 3.
Table 3: vitamin D in embodiment 1 to embodiment 5
3the measurement result of content
A series of detailed description listed is above only illustrating for feasibility embodiment of the present invention; they are also not used to limit the scope of the invention, all do not depart from the skill of the present invention equivalent implementations done of spirit or change all should be included within protection scope of the present invention.
To those skilled in the art, obviously the invention is not restricted to the details of above-mentioned one exemplary embodiment, and when not deviating from spirit of the present invention or basic feature, the present invention can be realized in other specific forms.Therefore, no matter from which point, all should embodiment be regarded as exemplary, and be nonrestrictive, scope of the present invention is limited by claims instead of above-mentioned explanation, and all changes be therefore intended in the implication of the equivalency by dropping on claim and scope are included in the present invention.Any Reference numeral in claim should be considered as the claim involved by limiting.
In addition, be to be understood that, although this description is described according to embodiment, but not each embodiment only comprises an independently technical scheme, this narrating mode of description is only for clarity sake, those skilled in the art should by description integrally, and the technical scheme in each embodiment also through appropriately combined, can form other embodiments that it will be appreciated by those skilled in the art that.
Claims (10)
1. a calcium carbonate D
3sheet, is characterized in that, comprises following component by weight:
Paris white 1250g, vitamin d3 powder 2g, disintegrating agent 6.5g, lubricant 1g and other medically acceptable adjuvant 170g, described medically acceptable adjuvant contains microcrystalline Cellulose 102, and the weight content of microcrystalline Cellulose 102 is up to 4%.
2. calcium carbonate D according to claim 1
3sheet, is characterized in that, described medically acceptable adjuvant comprises binding agent, wetting agent and filler.
3. calcium carbonate D according to claim 2
3sheet, is characterized in that, described binding agent is hypromellose, polyvidone, starch, pregelatinized Starch, dextrin, microcrystalline Cellulose, methylcellulose or ethyl cellulose.
4. calcium carbonate D according to claim 2
3sheet, is characterized in that, described wetting agent is selected from ethanol or purified water.
5. calcium carbonate D according to claim 2
3sheet, is characterized in that, described filler is selected from starch, dextrin, lactose, glucose, pregelatinized Starch or mannitol.
6. calcium carbonate D according to claim 1
3sheet, is characterized in that, described disintegrating agent is polyvinylpolypyrrolidone, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose or hydroxypropyl starch.
7. calcium carbonate D according to claim 1
3sheet, is characterized in that, described lubricant is magnesium stearate, stearic acid or micropowder silica gel.
8. a calcium carbonate D as claimed in claim 1
3the preparation method of sheet, is characterized in that, comprises the following steps:
Step 1): Paris white adds wetting agent after mixing homogeneously with medically acceptable adjuvant and obtains soft material;
Step 2): soft material is crossed 30 eye mesh screen pelletizes and is obtained wet granular;
Step 3): under wet granular is placed in 60 DEG C ~ 70 DEG C conditions, dried obtains the dry granule that moisture content is 1% ~ 2%;
Step 4): vitamin D
3powder is pulverized and is crossed 100 eye mesh screens;
Step 5): by step 3) in dry granule with cross the vitamin D of 100 eye mesh screens
3powder, disintegrating agent, lubricant and medically acceptable adjuvant mix homogeneously, tabletting.
9. calcium carbonate D according to claim 8
3the preparation method of sheet, is characterized in that, described step 3) in the baking temperature of wet granular be 60 DEG C.
10. calcium carbonate D according to claim 8
3the preparation method of sheet, is characterized in that, the particle diameter D of described microcrystalline Cellulose 102
15be 45 ± 2 μm, D
85be 60 ± 1.5 μm, porosity (5.0 ± 0.4) × 10
-5cm
3/ g.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108478595A (en) * | 2018-05-01 | 2018-09-04 | 王康俊 | A kind of pharmaceutical composition containing calcium carbonate, vitamine D3, farnoquinone |
| CN109172531A (en) * | 2018-09-04 | 2019-01-11 | 安士制药（中山）有限公司 | A kind of composite calcium carbonate/vitamin D3Tablet and preparation method thereof |
| CN109364036A (en) * | 2018-11-15 | 2019-02-22 | 海南赛立克药业有限公司 | A kind of calcium carbonate D3Piece and preparation method thereof |
| CN110354091A (en) * | 2019-07-17 | 2019-10-22 | 宿迁市现代生物科技股份有限公司 | A kind of formula of the granular calcium carbonate of health care product directly compressible |
| CN110755448A (en) * | 2019-11-18 | 2020-02-07 | 安士制药（中山）有限公司 | Compound calcium carbonate chewable tablet capable of effectively improving calcium absorption rate and preparation method thereof |
| CN111494408A (en) * | 2020-04-28 | 2020-08-07 | 广东润源中天生物科技有限公司 | Calcium vitamin D3 tablet and production method thereof |
| CN115737586A (en) * | 2022-12-06 | 2023-03-07 | 南京比逊医药科技有限公司 | Preparation method of calcium carbonate D3 tablet with stable components |
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|---|---|---|---|---|
| CN1587056A (en) * | 2004-07-09 | 2005-03-02 | 胡志彤 | High purity medicinal calcium carboante and its producing method |
| CN102085216A (en) * | 2009-12-07 | 2011-06-08 | 胡志彤 | High-density calcium carbonate tablet and preparation method thereof |
| US20130085121A1 (en) * | 2011-09-30 | 2013-04-04 | Jianguo Wang | Pharmaceutical compositions comprising phosphate binder, calcium receptor-active compound and/or active vitamin d |
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2015
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1587056A (en) * | 2004-07-09 | 2005-03-02 | 胡志彤 | High purity medicinal calcium carboante and its producing method |
| CN102085216A (en) * | 2009-12-07 | 2011-06-08 | 胡志彤 | High-density calcium carbonate tablet and preparation method thereof |
| US20130085121A1 (en) * | 2011-09-30 | 2013-04-04 | Jianguo Wang | Pharmaceutical compositions comprising phosphate binder, calcium receptor-active compound and/or active vitamin d |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108478595A (en) * | 2018-05-01 | 2018-09-04 | 王康俊 | A kind of pharmaceutical composition containing calcium carbonate, vitamine D3, farnoquinone |
| CN109172531A (en) * | 2018-09-04 | 2019-01-11 | 安士制药（中山）有限公司 | A kind of composite calcium carbonate/vitamin D3Tablet and preparation method thereof |
| CN109364036A (en) * | 2018-11-15 | 2019-02-22 | 海南赛立克药业有限公司 | A kind of calcium carbonate D3Piece and preparation method thereof |
| CN110354091A (en) * | 2019-07-17 | 2019-10-22 | 宿迁市现代生物科技股份有限公司 | A kind of formula of the granular calcium carbonate of health care product directly compressible |
| CN110755448A (en) * | 2019-11-18 | 2020-02-07 | 安士制药（中山）有限公司 | Compound calcium carbonate chewable tablet capable of effectively improving calcium absorption rate and preparation method thereof |
| CN111494408A (en) * | 2020-04-28 | 2020-08-07 | 广东润源中天生物科技有限公司 | Calcium vitamin D3 tablet and production method thereof |
| CN115737586A (en) * | 2022-12-06 | 2023-03-07 | 南京比逊医药科技有限公司 | Preparation method of calcium carbonate D3 tablet with stable components |
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