CN106138005A - Good calcium carbonate vitamin C effervescent tablet of a kind of effervesce effect and preparation method thereof - Google Patents
Good calcium carbonate vitamin C effervescent tablet of a kind of effervesce effect and preparation method thereof Download PDFInfo
- Publication number
- CN106138005A CN106138005A CN201610637854.XA CN201610637854A CN106138005A CN 106138005 A CN106138005 A CN 106138005A CN 201610637854 A CN201610637854 A CN 201610637854A CN 106138005 A CN106138005 A CN 106138005A
- Authority
- CN
- China
- Prior art keywords
- vitamin
- calcium carbonate
- effervescent tablet
- leucine
- carbonate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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Abstract
The invention discloses good calcium carbonate vitamin C effervescent tablet of a kind of effervesce effect and preparation method thereof, described effervescent tablet is made up of vitamin C, calcium carbonate, mannitol, anhydrous citric acid, sodium acid carbonate, honey element, leucine, the effervescent tablet sweet and sour taste that the present invention makes, effervesce effect is good, solution clarification after effervesce, is suitable for crowd wide, not sugary, applicable diabetic takes, and does not contains pigment, essence, to healthy more harmless.
Description
Invention field:
The present invention relates to good calcium carbonate vitamin C effervescent tablet of a kind of effervesce effect and preparation method thereof, belong to medicine
Technical field.
Technical background:
Vitamin C is the necessary vitamin of human body, supports the system of defense of health.Everyone can not lack vitamin C,
Especially smoker, sportsman, pregnant woman and nursing women are with greater need for increase Vitamin C Supplementation.Calcium is the required unit of organism
Element.For human body, no matter in muscle, nerve, body fluid and bone, all useful Ca2 +In conjunction with protein.Calcium is mankind's bone, tooth
Main inorganic composition, be also neurotransmission, contraction of muscle, blood clotting, hormone release and the necessary unit such as galactosis
Element.Calcium accounts for the 1.4% of body mass, participates in metabolism, must be supplemented with calcium every day;In human body, calcium content deficiency or surplus are all
Can affect and grow and healthy.Research shows, hypovitaminosis C, collagen synthesis obstacle, so that ossein is formed not
Good and cause osteoporosis.Children often show a kind of prominent feature, and i.e. long epiphysis is shaft-like deformity, ache during joint motion
Bitterly, infant often makes knee joint keep flexing position.Rib and costal cartilage intersection substantially highlight in beading, and its angle compares rickets
Beading are slightly sharp;Can lay one's hand on and cave in protruding inner side;Rachitic bead then bilateral symmetry, without depressed area, inner side.
For diseases such as treatment osteoporosises, the effervescent tablet much made with vitamin C for primary raw material occurs on the market, but
When existing effervescent tablet makes, technological parameter is not also quite reasonable so that the effervescent tablet stability made is bad, easily goes out after listing
Now rise the problems such as bag, variable color and effervesce effect decay.Additionally, the existing effervescent tablet made with vitamin C for raw material possibly together with sugar,
Pigment, essence etc..Can not eat for requiring supplementation with the diabetes patient of vitamin C and calcium, and pigment and essence are mostly
It is that chemical addition agent is harmful to healthy.
Content of the invention:
The technical problem to be solved be to provide the calcium carbonate vitamin C effervescent tablet that a kind of effervesce effect is good and
Its preparation method.The effervescent tablet good stability that described method is made, does not haves the bag that rises, variable color and effervesce effect decay etc. and asks
Topic, and solution clarification after effervesce, be suitable for crowd wide, and not sugary, applicable diabetic takes, and does not contains pigment, essence, to health
Health is more harmless.Effervescent tablet of the present invention can also promoting bone growing, have increase bone density effect, can effectively treat sclerotin dredge
Pine.
For solving above-mentioned technical problem, the present invention realizes by the following technical solutions:
The good calcium carbonate vitamin C effervescent tablet of a kind of effervesce effect, calculates according to composition by weight, mainly by vitamin C
800-1200 part, calcium carbonate 300-400 part, mannitol 900-1300 part, anhydrous citric acid 800-1200 part, sodium acid carbonate 500-
700 parts, honey element 100-200 part, leucine 100-150 part makes.
The good calcium carbonate vitamin C effervescent tablet of aforesaid effervesce effect, calculates according to composition by weight, mainly by vitamin C
1000 parts, 250 parts of calcium carbonate, 1100 parts of mannitol, anhydrous citric acid 1000 parts, sodium acid carbonate 600 parts, honey element 156 parts, bright
Propylhomoserin 125 parts is made.
The preparation method of the good calcium carbonate vitamin C effervescent tablet of a kind of aforementioned effervesce effect, temperature 18~26 DEG C, relatively
Sodium acid carbonate and vitamin C, calcium carbonate, mannitol, anhydrous citric acid, honey element are mixed all by environment below 45% for the humidity
Even, dry granulation, add leucine always to mix, mix, omnidistance granulation, total mixed, particle or the direct ingress of air of medicinal powder
Must not exceed 4 hours, compression mold washes of absolute alcohol, hair dryer dries up rear compressing tablet, packaging, to obtain final product.
In the preparation method of the good calcium carbonate vitamin C effervescent tablet of aforesaid effervesce effect, described sodium acid carbonate is so made
Standby: temperature 18~26 DEG C, environment below 45% for the relative humidity, 100 DEG C of dryings of silica gel particle 5 hours are airtight, put to room
Temperature, then sodium bicarbonate fine powder is mixed with silica gel particle 1:1, airtight, it is dried 18 hours in 40 DEG C of environment, sieve, remove silicon
Glue particle, to obtain final product.
In the preparation method of the good calcium carbonate vitamin C effervescent tablet of aforesaid effervesce effect, described vitamin C, calcium carbonate,
Mannitol, anhydrous citric acid, honey element, leucine are prepared: by vitamin C, anhydrous citric acid, calcium carbonate, leucine, sweet
Honey element is respectively at vacuum > 0.87Mmpa, temperature is to be dried sealing in 2 hours under conditions of 40 DEG C, puts to room temperature, to obtain final product.
Vitamin C is acid hexose derivative, is dilute alcohol of formula saccharinic acid lactone, Vc main source fresh fruit and vegetables,
It is the essential nutrients of High Primates animal and other minorities biologies, supplement calcium during replenishing vitamins C simultaneously, enhancing can be played
The osteoporosis effect that treatment hypovitaminosis C causes.When treating vitamin C deficiency, general recipe quantity is 1g/ days, because of
The good effervescent tablet every Vitamin C content of this effervesce effect of the present invention is 1g, it is ensured that daily amount reaches 1g standard.The present invention
Good effervescent tablet every calcium carbonate 0.25g of effervesce effect (i.e. calcic 100mg), according to " Chinese residents diet nutrient reference
Intake ", food intake and other absorption modes such as every day, calcium demand was 800mg, deduction milk, supplement 100mg calcium every day
Both can help to prevent and treat calcium deficiency card, be also unlikely to supplement the calcium amount exceeding needed for health simultaneously, vitamin C can be effectively treated
Lack the osteoporosis causing.
Applicant has also carried out long-term substantial amounts of research, first, applicant to the manufacture craft of effervescent tablet of the present invention
Process to sodium acid carbonate in raw material is studied, it has been found that more than 45 degree dryings of sodium acid carbonate, easily generates carbonic acid
Sodium, sodium carbonate water imbibition is very strong, absorbs compared with juicy, and effervescent tablet is susceptible to spontaneous acid-base reaction.Directly contribute compressing tablet work
Profit sent out by sequence material, and pressure is not in blocks, and causes the bag that rises after later product listing, variable color and the decay of effervesce effect.Therefore, apply for
People uses following method to process sodium acid carbonate: i.e. temperature 18~26 DEG C, environment below 45% for the relative humidity, by silica gel particle
100 DEG C of dryings 5 hours are airtight, put to room temperature, then mix sodium bicarbonate fine powder with silica gel particle 1:1, airtight, in 40 DEG C of environment
Middle drying 18 hours, sieves, removes silica gel particle, to obtain final product.The sodium acid carbonate so made is made present invention bubble as raw material
Rising piece, the effervescent tablet quality made is good, and for white, effervesce effect is good, does not haves rise bag, variable color etc..Secondly, applicant is to dimension
Raw element C, calcium carbonate, mannitol, anhydrous citric acid, honey element, leucic process are studied, and vitamin C 75 DEG C is done
Dry, can turn to be yellow when water content height, the time is longer, turns to be yellow more serious, finished product effervescent tablet can be caused to have and faint yellow do not meet quality
Require.Applicant finds through lot of experiments, and vitamin C is vacuum dried 2 hours (vacuum > 0.87Mmpa) at 40 DEG C, not only
Can ensure that moisture drying is complete, and can ensure that color is unchanged, citric acid, calcium carbonate etc. are wanted without temperature and vacuum
Ask, but need to be separately dried;Combination drying is when material moisture height, easily owing to there is local acid-base reaction conglomeration caking.This
Outward, the preparation method of effervescent tablet of the present invention is also studied by applicant, and applicant begins with wet granulation, Ji Jianggan most
Citric acid after dry, calcium carbonate, honey element, sodium acid carbonate mix, and absolute ethyl alcohol 12 mesh is pelletized, and (ethanol consumption is about particle
The 3/50 of amount), 75 DEG C of dryings 12 hours.Applicant have discovered that wet granulation 75 degree drying, have part sodium acid carbonate to change
For sodium carbonate, water imbibition is relatively strong, need to shorten the time of contact with workshop air (below humidity 50%) so that time of contact allows
Scope little, wayward.During it has been found that use preparation method of the present invention to make effervescent tablet of the present invention, time of contact permits
The scope permitted is big, easy to control.The present invention controls particle or the direct ingress of air of medicinal powder must not exceed 4 hours, so can avoid
The medicine moisture absorption, to reach to ensure the purpose of finished product effervescent tablet quality so that the effervescent tablet quality made is good.And the effervescent tablet made
Mouthfeel is sour-sweet taste, tablet white, and during effervesce, gas production is big, and effervesce effect is good, solution clarification after effervesce.In addition, the present invention
The additives such as effervescent tablet is not sugary, pigment and essence, applicable crowd is wider, is suitable for diabetic especially and takes, is good for health
Health is more favourable.
The following is the part Experiment that applicant is carried out:
Experimental example 1: technical study
1st, material
1.1 effervescent tablets of the present invention: be prepared by embodiment 1;
1.2 effervescent tablets 1:
Formula: vitamin C 1000g, calcium carbonate 250g, mannitol 1000g, anhydrous citric acid 1100g, sodium acid carbonate
600g, honey element 156g, leucine 125g.
Technique: comprising the steps: that in temperature be 18~26 DEG C, environment below 45% for the relative humidity, by silica gel particle
100 DEG C of dryings 5 hours are airtight, put to room temperature, then mix sodium bicarbonate fine powder with silica gel particle 1:1, airtight, in 60 DEG C of environment
Middle drying 18 hours, sieves, removes silica gel particle, and the sodium acid carbonate both must prepared is standby;By vitamin C, citric acid, carbonic acid
Calcium, leucine, honey element are respectively at vacuum > 0.87Mmpa, temperature is to be dried sealing in 2 hours under conditions of 40 DEG C, puts to room
Temperature, the vitamin C both must prepared, citric acid, calcium carbonate, leucine, honey element, seal standby;By preparation sodium acid carbonate and
The vitamin C of preparation, calcium carbonate, mannitol, anhydrous citric acid, honey element mix, dry granulation, add the bright ammonia of preparation
Acid always mixes, and mixes, and omnidistance granulation, total mixed, particle or the direct ingress of air of medicinal powder must not exceed 4 hours, and mould is used
Washes of absolute alcohol, after hair dryer dries up, compressing tablet, in a dry environment, load tablets separated in packing tube, pack.
1.3 effervescent tablets 2:
Formula: vitamin C 1000g, calcium carbonate 250g, mannitol 1100g, anhydrous citric acid 1000g, sodium acid carbonate
500g, honey element 206g, leucine 175g.
Technique: comprising the steps: that in temperature be 18~26 DEG C, environment below 45% for the relative humidity, by silica gel particle
100 DEG C of dryings 5 hours are airtight, put to room temperature, then mix sodium bicarbonate fine powder with silica gel particle 1:1, airtight, in 40 DEG C of environment
Middle drying 18 hours, sieves, removes silica gel particle, and the sodium acid carbonate both must prepared is standby;By vitamin C, citric acid, carbonic acid
Calcium, leucine, honey element, respectively at 75 DEG C of dryings 18 hours, let cool to room temperature in closed environment, standby.Both the dimension must prepared
Raw element C, citric acid, calcium carbonate, leucine, honey element, seal standby;By vitamin C, the carbon of the sodium acid carbonate prepared and preparation
Acid calcium, mannitol, anhydrous citric acid, honey element mix, dry granulation, add the leucine of preparation always to mix, mixing
Uniformly, omnidistance granulation, total mixed, particle or the direct ingress of air of medicinal powder must not exceed 4 hours, mould washes of absolute alcohol, electricity
After drying up, compressing tablet, in a dry environment, load tablets separated in packing tube, pack, to obtain final product.
1.4 effervescent tablets 3:
Formula: vitamin C 1000g, calcium carbonate 250g, mannitol 1200g, anhydrous citric acid 900g, sodium acid carbonate
500g, honey element 176g, leucine 105g.
Technique: comprising the steps: that in temperature be 18~26 DEG C, environment below 45% for the relative humidity, by silica gel particle
100 DEG C of dryings 5 hours are airtight, put to room temperature, then mix sodium bicarbonate fine powder with silica gel particle 1:1, airtight, in 40 DEG C of environment
Middle drying 18 hours, sieves, removes silica gel particle, and the sodium acid carbonate both must prepared is standby;By vitamin C, citric acid, carbonic acid
Calcium, leucine, honey element are respectively at vacuum > 0.87Mmpa, temperature is to be dried sealing in 2 hours under conditions of 40 DEG C, puts to room
Temperature, standby.Both the vitamin C that must prepare, citric acid, calcium carbonate, leucine, honey element, seal standby;By dried citron
Acid, calcium carbonate, honey element, sodium acid carbonate mix, and add the absolute ethyl alcohol of newly open 6%, are pelletized by 12 mesh, do for 75 DEG C
Dry 12 hours.The 12 whole grains of mesh, cross 80 mesh sieves after whole grain, fine powder gives over to chieftain, airtight add such as 100 DEG C of dryings 5 hours and are cooled to
Room temperature such as bagged dryer, particle mixes with the leucine being dried after processing, is placed in airtight stainless steel cask, is simultaneously introduced 100
DEG C drying 5 hours is simultaneously cooled to the whole grain of bagged dryer all processes of room temperature, sieves, mixes and need to complete in 2 hours, it is ensured that
Medicinal powder, particle are exposed to clean area air time and are less than 2 hours.Mould washes of absolute alcohol, after hair dryer dries up, pressure
Piece, in a dry environment, loads tablets separated in packing tube, packs, to obtain final product.
2 tests
Taking above-mentioned effervescent tablet respectively, testing, test event and test result are shown in Table 1:
The good calcium carbonate vitamin C effervescent tablet inspection of effervesce effect prepared by table 1 different kinds of process flow
3 conclusions
1st, more than 45 DEG C dryings of sodium acid carbonate, easily generate sodium carbonate, and sodium carbonate water imbibition is very strong, absorbs more water
Point, the effervescent tablet of production is susceptible to spontaneous acid-base reaction.Directly contribute sheeting process material and send out profit, it is impossible to be pressed into piece, later stage
Bag, variable color and the effervesce effect of rising after launch decays.
2nd, vitamin C is at 75 DEG C, and drying under the high environment of water content can be turned to be yellow, but acceptable, and the time is oversize, and jaundice is tight
Weight, causes slice, thin piece to have the faint yellow quality requirement that do not meets, and vitamin C is vacuum dried 2 hours at 40 DEG C, not only can ensure moisture
It is dried completely, and can ensure that color is unchanged.
3rd, citric acid, calcium carbonate, leucine, honey element dry run are without temperature and vacuum level requirements, but need to be separately dried;
Combination drying is when material moisture height, easily owing to there is local acid-base reaction conglomeration caking.
4th, the shortcoming of wet granulation technology needs 75 degree of dryings for pelletizing, and has part sodium acid carbonate to be converted to sodium carbonate, inhales
Aqueous enhancing, therefore, Workshop Production control need to be shortened and time of contact below 45% for the workshop air humidity as far as possible;Dry method system
Grain, will not generate sodium carbonate, and the air humidity in slice, thin piece and workshop can allow more wide in range time of contact below 45%, but still
Need control;Under different humidity environment, the general performance of the slice, thin piece i.e. hygroscopicity of weight change and chemical reaction is shown in Fig. 1.
Brief summary: abscissa is hour.Icon proof humid control is below 28%, and method one and method two are all non-hygroscopic,
But actual production environment can not reach this to be required;Therefore, by control particle and air contact time in actual production process
Control water absorption, to reach to ensure the purpose of product quality.Use special effervescent tablet to pack during packaging, be possible to prevent product
The problem of moisture absorption during storing.
Experimental example 2: pharmacological evaluation
(1) function of resisting osteoporosis to ovariectomized female rats
1st, material
Effervescent tablet of the present invention (method as described in embodiment 1 is prepared), rat IGF-1 and IL-6 quantitative determination reagent,
ELISA kit, Senxiong Science & Technology Industry Co., Ltd., Shanghai;Gegenbaur's cell BMP-2 expresses and measures reagent, and Wuhan doctor's moral is biological
Engineering Co., Ltd;DEXA dual energy X-ray absorptimetry, Hologic company of the U.S.;Biomicroscope, Shanghai Cai Kang optical instrument
Factory.3 monthly age cleaning grade Wister female rats, body weight 180~220g, Guiyang Medical College provides.
2nd, method
2.1 animal packets
60 female rats, are randomly divided into sham-operation group, model group, Nilestriol group, effervescent tablet of the present invention low, medium and high
Dosage group, often organizes 10.
2.2 animal process
Rat is after yellow Jackets intraperitoneal anesthesia, and under aseptic condition, complete resection ovary, layering after hemostasis is sewed up, false
Operation group does identical operation technique, but does not excise ovary, only a little fat of excision.It is in postoperative 5d, anti-infective with gentamicin,
Freely drink water, ingest.
2.3 feeding methods and index determining
Operation one week after starts gavage feed.Nilestriol group gavage Nilestriol 0.5mg/kg, 2 times a week (Monday and
Thursday);The other gavage of the low, medium and high dosage component of effervescent tablet of the present invention effervescent tablet of the present invention, the 0.3rd, 0.6 and 0.9g/kg, Neil is female
Alcohol and effervescent tablet of the present invention are all suspended with 0.5%CMC-Na solution;Sham-operation group and the equal gavage of model group give 0.5%CMC-Na
Solution.Weighing once weekly, and adjusting given low, total administration time is 70d.The experiment end of term, sacrificed by decapitation rat, peels off
Left femur, by borne densitometers measurement rat femur midpoint and distal end bone density, takes blood, centrifugal, takes serum, by ELISA examination
Agent box operation instruction quantitative determination serum I GF-1 and IL-6;Use Immunohistochemical Method to measure the expression of calvarial cells BMP-2, take
Right side parietal bone cranium is inserted rapidly in 4% paraformaldehyde solution fixing, prepares histotomy, and biology microscope sem observation every is cut
Piece, selects 2 visuals field to do Gegenbaur's cell sum and positive counting, averages.
2.4 statistical analysis
Respectively organize the positive rate of BMP-2 with Chi-square Test.Other data SPSS10.0 version softwares are analyzed,
Result represents with (x ± s), compares and use one-way analysis of variance between group, and P < 0.05 indicates significant difference.
3rd, result
The measurement result of 3.1BMD
The results are shown in Table 2.The femur center bone density of model group and distal end bone density substantially reduce (P < than sham-operation group
0.05);Compared with model group, Nilestriol group, the femur center bone density of effervescent tablet of the present invention low, medium and high dosage group and remote
Heart end bone density substantially increases (P < 0.05).
The impact (n=10, x ± s) on ovariectomized female rats bone density for the table 2
Note: compare with sham-operation,1P < 0.05;
Compare with model group,2P < 0.05,3P < 0.01.
3.2 serum I GF-1 and IL-6
The results are shown in Table 3.Sham-operation group, Nilestriol group serum I GF-1 level compare with model group, and conspicuousness increases (P <
0.01), effervescent tablet of the present invention low, medium and high dosage group compared with model group without explicitly difference (P > 0.05).Nilestriol
Group, effervescent tablet of the present invention low, medium and high dosage group IL-6 compare with sham-operation group that there was no significant difference (P >
0.05), compare with model group and significantly reduce (P < 0.01).
The impact (n=10, x ± s) on ovariectomized female rats serum I GF-6 and IL-6 level for the table 3
Note: compare with model group,1P < 0.05.
3.3BMP-2 express
The results are shown in Table 4.Nilestriol group, effervescent tablet of the present invention low, medium and high dosage group BMP-2 positive rate are apparently higher than mould
Type group (P < 0.01);No significant difference between sham-operation group and model group.
The impact (n=10, x ± s) of the expression on ovariectomized female rats Calvarial osteoblast Bones morphology BMP-2 for the table 4
Note: compare with model group:1P < 0.01;2P < 0.05.
Developing under the regulation of Gegenbaur's cell various Control factors in vivo, BMP-2 is one of major regulatory factor.
It is osteoblastic conversion promotive factor that BMP-2 has been recognized.In Gegenbaur's cell, BMP-2 expresses and increases, cell autocrine BMP-2
Increasing, Gegenbaur's cell regulates the propagation of himself, differentiation and metabolism in the way of autocrine, also can synthesize, secretion more than 20 kind glue
Former with NCP matter and some Bone m etabolism local modulation factors, bone remoulding generates osteoid, repairing osteoclastic bone
Absorb the lacuna being formed, promote osteoid mineralising, thus to the growing of bone tissue, injury repair, Bone m etabolism balance and bone
Amount maintenance etc. plays key effect.In this research, effervescent tablet of the present invention makes Gegenbaur's cell and osteocyte BMP-2 the positive expression rate increase
Add, significant difference (P < 0.01) compared with model group.As can be seen here, effervescent tablet of the present invention can pass through stimulating osteoblast BMP-2
Express promoting bone growing.
In sum, effervescent tablet energy promoting bone growing of the present invention, has the effect increasing bone density.
(2) present invention increases the research of bone substance density improving function
1. material
1.1 effervescent tablets of the present invention (method as described in embodiment 1 is prepared).
1.2 animal
SPF level male SD rat 55, body weight 65-75g, Guiyang Medical College provides.
1.3 feed
Low calcium feed formula (gram %): casein 10.0, analysis for soybean powder 15.0, wheat flour 54.0, peanut oil 4.0, cellulose
2.0, AIN-76 salt-mixtures 2.6, AIN-76 mixed vitamin 1.0, Choline Chloride 0.2, DL-METHIONINE 0.2, starch 11.0, real
Surveying per kilogram feed contents is 789.5mg, adds CaCO3 to make feed calcium content reach to survey 150mg/100g, raises as low calcium
Material.In whole experimentation, animal freely ingests and drinks deionized water.
2nd, experimental technique
It after rat is fed with seven days by basal feed adaptability, according to body weight, is randomly divided into following five groups: low calcium control group,
High dose calcium carbonate group, eat effervescent tablet of the present invention three dosage groups: 250mg/kb.bw group, 500mg/kb.bw group with
1000mg/kb.bw group (is respectively equivalent to the 5th, the 10th, 20 times of human intaking amount 50mg/kb.bw), every treated animal 11.Five groups big
Mouse is all fed with by low calcium feed.Mg/kb.bw is shone group with distilled water gavage by low calcium;Three dosage groups fill with the sample liquid configuring
Stomach (preparation of gavage liquid: take effervescent tablet of the present invention respectively, adds distilled water and is settled to 100ml, be configured to 250mg/kb.bw,
The gavage liquid of 500mg/kb.bw and 1000mg/kb.bw group);High dose calcium carbonate control group per os pours into 334mg/kb.bw's
Calcium carbonate, this dosage is equivalent to effervescent tablet high dose group calcium level of the present invention, and all animal gavage amounts are 10mg/kb.bw, often
It once, continuous gavage 90 days, weigh weekly and by body weight adjust gavage amount.Experiment end femoral artery sacrificed by exsanguination animal, takes
Go out right side femur, in 105 DEG C of baking ovens, bake to constant weight, claim bone measurement.Use the scanning of DXP-L Dual-energy X-rays absorptionmetry whole left
Femur, represents this bone bone density with the mean bone density of bone.Use atomic absorption spectroscopy determination right femur calcium content.
3rd, experimental data statistics
Use PEMS3.1 statistical package, variance analysis is made to the group difference of each index.
4th, result
The impact on rat body weight and bone weight for 4.1 effervescent tablets of the present invention, is shown in Table 5.
The impact (x ± s) on rat body weight, bone weight for the table 5
Note: compare P < 0.01 with low calcium control group.
From table 5, body weight and low calcium pair before the experiment of three dosage groups of effervescent tablet of the present invention and high dose calcium carbonate group
According between group, there was no significant difference (P > 0.05);After experiment, high dose calcium carbonate in combination and three dosage group body weight are significantly higher than
Low calcium control group (P < 0.01).Right femur bone weight and the low calcium of three dosage groups of this effervescent tablet of the present invention and high dose calcium carbonate group
Control group compares, and has rising trend, but without statistics meaning (P > 0.05).
The impact on rat bone density and calcium content of bone for 4.2 effervescent tablets of the present invention
It is specifically shown in Table 6.
The impact (x ± s) on rat bone density and calcium content of bone for the table 6
Note: compare P < 0.05 with low calcium control group
From table 6, the bone density of high dose group calcium carbonate is significantly higher than low calcium control group (P < 0.05) effervesce of the present invention
The bone density of three dosage groups of piece is significantly higher than low calcium control group (P < 0.05), and high dose group fl bone density and high dose
Between calcium carbonate control group, there was no significant difference (P > 0.05).The right femur calcium content of three dosage groups of effervescent tablet of the present invention with low
Calcium control group compares increase trend, but not statistically significant (P > 0.05).
5th, result
After experiment three dosage groups of effervescent tablet of the present invention and high dose calcium carbonate group body weight be significantly higher than low calcium control group (P <
0.01), the fl bone density of three dosage groups is apparently higher than low calcium control group (P > 0.05), high dose group fl bone density
Compare no significant difference (P > 0.05) with high dose calcium carbonate control group, and Growth in Rats had no adverse effects, it can be seen that, this
Invention effervescent tablet has the function increasing bone density.
Experimental example 3: study on the stability
1st, three batches, sample
Effervescent tablet 1 of the present invention: be designated as sy-121, is prepared by embodiment 1;
Effervescent tablet 2 of the present invention: be designated as sy-122, is prepared by embodiment 1;
Effervescent tablet 3 of the present invention: be designated as sy-123, is prepared by embodiment 1;
2nd, reagent reagent:
Absolute ethyl alcohol, silver nitrate test solution, sodium dichlorophenol indophenolate, 2mol/L ammonium chloride solution, 0.25mol/L sodium sulfide solution,
Glycerine, ammonium oxalate test solution, watery hydrochloric acid, calcium hydroxide test solution, Rose Bengal Sodium agar medium, nutrient agar, cholate breast
Sugar culture-medium, MUG cultivation, pH7.0 sterile NaCl-peptone buffer agent etc..
3rd, instrument:
Electronic balance (INSTRUMENT MODEL: JJ500, instrument numbering: HF-JXSB-443);
Electric-heated thermostatic water bath (INSTRUMENT MODEL: 420 class, instrument numbering: HF-JXSB-394);
Desk-top drying box (INSTRUMENT MODEL: WG2003, instrument numbering: HF-JXSB-408);
Constant incubator (INSTRUMENT MODEL: SPX-250BIII, instrument numbering: HF-JXSB-459);
Electric heating thermal insulation drying box (INSTRUMENT MODEL: CS202B, instrument numbering: HF-JXSB-415);
Refrigerator (INSTRUMENT MODEL: BCD-182, instrument numbering: HF-JXSB-419);
Vertical autoclave sterilizer (INSTRUMENT MODEL: LQ-400-50L instrument is numbered: HF-JXSB-436);
Magnetic stirring apparatus (INSTRUMENT MODEL: CJJ-931, instrument numbering: HF-JXSB-413).
4th, project is investigated
Proterties, discriminating, inspection, microbial limit, assay etc..
5th, method is investigated:
5.1 accelerated tests:
Three batch samples of commercially available back intended by delivery, place 6 under conditions of temperature 40 ± 2 DEG C, relative humidity 75 ± 5%
Individual month, produce of that month project of investigating as needed for compound calcium carbonate effervescent tablet quality standard method and tablet and carry out detecting and record,
As the result of 0 month.Then to test 1st month period, the 2nd month, the 3rd month, the 6th month separately sampled once, by multiple
Investigation project needed for side's calcium carbonate effervescing tablet quality standard method and tablet detects, and records result.
5.2 continuous stability tests:
Three batch samples that commercially available back intended by delivery place 6 under conditions of temperature 25 ± 2 DEG C, relative humidity 60 ± 10%
Individual month.Respectively at 0 month, 3 months, sampling in 6 months, investigate by compound calcium carbonate effervescent tablet quality standard method and tablet are required
Project carries out detecting and records result.
5.3 compound calcium carbonate effervescent tablet accelerated stabilities investigate result.
Table 7 compound calcium carbonate effervescent tablet stability test result table
Table 8 compound calcium carbonate effervescent tablet accelerated test result table
8th, conclusion:
Effervescent tablet sample prepared by the present invention under the conditions of accelerated test and placed half a year under room temperature condition, from 0 month, 1
From the point of view of the moon, February, March, acceleration in June and long-term investigation result, each investigation project all loses exception, all meets quality criteria requirements.
Illustrate that compound calcium carbonate effervescent tablet of the present invention has good stability, the bag that will not rise after simulation listing, variable color, the decline of effervesce effect.
Compared with prior art, the effervescent tablet sweet and sour taste that the present invention makes, effervesce effect is good, solution clarification after effervesce;
The crowd of being suitable for is wide, and not sugary, applicable diabetic takes, and does not contains pigment, essence, to healthy more harmless.The present invention steeps
Rise piece can also promoting bone growing, have increase bone density effect, can effectively treat osteoporosis.
Brief description:
The change of slice, thin piece weight under Fig. 1 different humidity environment.
Detailed description of the invention:
Experimental example 1.
Formula: vitamin C 1000g, calcium carbonate 250g, mannitol 1100g, anhydrous citric acid 1000g, sodium acid carbonate
600g, honey element 156g, leucine 125g.
Technique: comprising the steps: that in temperature be 18~26 DEG C, environment below 45% for the relative humidity, by silica gel particle
100 DEG C of dryings 5 hours are airtight, put to room temperature, then mix sodium bicarbonate fine powder with silica gel particle 1:1, airtight, in 40 DEG C of environment
Middle drying 18 hours, sieves, removes silica gel particle, both.Both the sodium acid carbonate must prepared, standby;By vitamin C, citric acid,
Calcium carbonate, leucine, honey element are respectively at vacuum > 0.87Mmpa, temperature is to be dried sealing in 2 hours under conditions of 40 DEG C, puts
To room temperature, the vitamin C both must prepared, citric acid, calcium carbonate, leucine, honey element, seal, standby;Bicarbonate by preparation
The vitamin C of sodium and preparation, calcium carbonate, mannitol, anhydrous citric acid, honey element mix, dry granulation, add preparation
Leucine always mixes, and mixes, and omnidistance granulation, total mixed, particle or the direct ingress of air of medicinal powder must not exceed 4 hours, mould
Tool washes of absolute alcohol, after hair dryer dries up, compressing tablet, in a dry environment, load tablets separated in packing tube, wrap
Dress, the existing commutation of packaging cover is used.
Usage: after lid packaging is taken apart, need to use in 2 hours completely.
Experimental example 2.
Formula: vitamin C 800g, calcium carbonate 300g, mannitol 900g, anhydrous citric acid 800g, sodium acid carbonate 500g,
Honey element 100g, leucine 100g.
Manufacture craft: with embodiment 1.
Usage is with embodiment 1.
Experimental example 3.
Formula: vitamin C 1200g, calcium carbonate 400g, mannitol 1300g, anhydrous citric acid 1200g, sodium acid carbonate
700g, honey element 200g, leucine 150g.
Manufacture craft: with embodiment 1.
Usage is with embodiment 1.
Claims (5)
1. the good calcium carbonate vitamin C effervescent tablet of an effervesce effect, it is characterised in that: calculate according to composition by weight, mainly by
Vitamin C 800-1200 part, calcium carbonate 300-400 part, mannitol 900-1300 part, anhydrous citric acid 800-1200 part, carbonic acid
Hydrogen sodium 500-700 part, honey element 100-200 part, leucine 100-150 part are made.
2. the good calcium carbonate vitamin C effervescent tablet of effervesce effect as claimed in claim 1, it is characterised in that: according to weight group
Part calculates, mainly by vitamin C 1000 parts, 250 parts of calcium carbonate, 1100 parts of mannitol, anhydrous citric acid 1000 parts, bicarbonate
600 parts of sodium, honey element 156 parts, leucine 125 parts are made.
3. a preparation method for the good calcium carbonate vitamin C effervescent tablet of effervesce effect as claimed in claim 1 or 2, its feature
Be: temperature 18~26 DEG C, environment below 45% for the relative humidity, by sodium acid carbonate and vitamin C, calcium carbonate, mannitol,
Anhydrous citric acid, honey element mix, dry granulation, add leucine always to mix, mix, omnidistance pelletize, total mixed,
Particle or the direct ingress of air of medicinal powder must not exceed 4 hours, compression mold washes of absolute alcohol, and hair dryer dries up rear compressing tablet,
Packaging, to obtain final product.
4. the preparation method of the good calcium carbonate vitamin C effervescent tablet of effervesce effect as claimed in claim 3, it is characterised in that:
Described sodium acid carbonate is prepared: at temperature 18~26 DEG C, environment below 45% for the relative humidity, do silica gel particle 100 DEG C
Dry 5 hours airtight, puts to room temperature, then mixes sodium bicarbonate fine powder with silica gel particle 1:1, airtight, is dried in 40 DEG C of environment
18 hours, sieve, remove silica gel particle, to obtain final product.
5. the preparation method of the good calcium carbonate vitamin C effervescent tablet of effervesce effect as claimed in claim 3, it is characterised in that:
Described vitamin C, calcium carbonate, mannitol, anhydrous citric acid, honey element, leucine are prepared: by vitamin C, anhydrous citron
Acid, calcium carbonate, leucine, honey element are respectively at vacuum > 0.87Mmpa, temperature is to be dried sealing in 2 hours under conditions of 40 DEG C,
Put to room temperature, to obtain final product.
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Cited By (3)
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CN112107553A (en) * | 2020-08-21 | 2020-12-22 | 技源健康科技(江苏)有限公司 | Calcium carbonate effervescent tablet and preparation method thereof |
CN113117008A (en) * | 2021-04-30 | 2021-07-16 | 贵州汉方药业有限公司 | Preparation method of Zhibai Dihuang pills |
CN114010607A (en) * | 2021-10-12 | 2022-02-08 | 上海腾瑞制药股份有限公司 | Preparation method of oyster calcium carbonate chewable tablets |
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CN112107553A (en) * | 2020-08-21 | 2020-12-22 | 技源健康科技(江苏)有限公司 | Calcium carbonate effervescent tablet and preparation method thereof |
CN113117008A (en) * | 2021-04-30 | 2021-07-16 | 贵州汉方药业有限公司 | Preparation method of Zhibai Dihuang pills |
CN113117008B (en) * | 2021-04-30 | 2022-10-21 | 贵州汉方药业有限公司 | Preparation method of Zhibai Dihuang pills |
CN114010607A (en) * | 2021-10-12 | 2022-02-08 | 上海腾瑞制药股份有限公司 | Preparation method of oyster calcium carbonate chewable tablets |
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Address after: No. 118 Chuangwei Road, Shawen Town, Guiyang National High tech Industrial Development Zone, Guiyang City, Guizhou Province, 550080 Patentee after: HANFANG PHARMA CO.,LTD. Country or region after: China Address before: 550080 Jinyang science and Technology Industrial Park, high tech Industrial Development Zone, Guiyang City, Guizhou Province (No. 11, Duyun Road) Patentee before: HANFANG PHARMA CO.,LTD. Country or region before: China |