CN106880639A - Aspirin and compound enteric-coated of vitamin C and preparation method thereof - Google Patents
Aspirin and compound enteric-coated of vitamin C and preparation method thereof Download PDFInfo
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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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
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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
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
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Abstract
The invention provides compound enteric-coated of aspirin and vitamin C.The structure of enteric coatel tablets is followed successively by aspirin from inside to outside and vitamin C compound label, spacer layer coating and enteric layer are coated.The label is made up of the aspirin and vitamin C as active component with excipient, and the content that active component accounts for label is 48%~67%.Described excipient includes filler, disintegrant, antioxidant, glidant and lubricant.Compound enteric-coated label of the invention：Aspirin 20~60%, vitamin C 10~40%, filler 10~50%, disintegrant 5~30%, adhesive 0.5%~2%, antioxidant, glidant 0%~2% and lubricant 0.2~2% and insolated layer materials 1.0%~5.0%.Product dissolution rate of the present invention is fast, and steady quality has stronger Clinical practicability.Preparation method of the present invention is suitable to industrialized production, there is larger application value.
Description
Technical field
The present invention relates to pharmaceutical preparation, and in particular to aspirin and compound enteric-coated of vitamin C and its preparation side
Method.
Background technology
Aspirin, its English name is Aspirin, its chemical entitled 2- acetoxy-benzoic, its knot
Structure formula is as follows：
Molecular formula：C9H8O4, molecular weight：180.16.
Aspirin is salicylate class medicine in 1853, by the clinical practice of more than 100 years, it was demonstrated that to have
The antipyretic-antalgic and anti-inflammatory antirheumatic drug of effect, be widely used in treatment cold, flu, neuralgia, arthralgia,
Acute and chronic rheumatalgia and rheumatoid pain etc..Low-dosage aspirin has antiplatelet aggregative activity, is used for
Prevention and treatment ischemic heart disease, angina pectoris, cardiopulmonary infraction, cerebral thrombosis.
But, aspirin some shortcomings：Such as facile hydrolysis, its term of validity is short；Oral aspirin can be directly perverse
Sharp stomach lining causes epigastric discomfort and n and V, and long-term use easily causes mucosal lesion, causes gastric ulcer and stomach
Bleeding, blood coagulation disorders, salicylism reaction etc..
Vitamin C, its English entitled Vitamin C, is called ascorbic acid (L-Ascorbic Acid),
Its entitled 2,3,4,5,6- penta hydroxy group -2- hexenoic acid -4- lactone of chemistry, its structural formula is as follows：
Molecular formula：C6H8O6, molecular weight：176.12.
Vitamin C is acid hexose derivative, is dilute alcohol formula hexose acid lactone, there is two kinds of isomeries of L-type and D- types
Body, but only L-type just has a physiological function.Vitamin C has the synthesis for promoting collagen, treats bad
Blood disease, the atrophy of prevention root of the tooth, bleeding, prevention of arterial hardening, immunity that is anti-oxidant and improving human body etc. are more
Plant effect.Vitamin C as medicine or health treatment, while being also the auxiliary treatment medicine of various diseases.
Vitamin C is soluble in water, insoluble in organic solvent.But, its stabilization in sour environment meets air
Middle oxygen, heat, light, alkaline matter, particularly by the metal ion such as oxidizing ferment and copper trace, iron in the presence of, can
Promote its Oxidative demage.
Vitamin C in enzymatic is through changing reaction is played a role as confactor, so in flu, rheumatism
In the case of property arthritis, infectious diseases or physical stress, human body often increases its requirement.It is needed by human
L-sorbose be stored in leucocyte and blood platelet.When medical field finds to take vitamin C 500mg dosage,
Increase that aspirin dose can make in blood plasma that vitamin C concentration is raised and the concentration in leucocyte then declines, explanation
Aspirin can reduce leucocyte to ascorbic absorption.Such as give the aspirin of 600mg, then can be complete
Suppress leucocyte to ascorbic absorption.Therefore, when doctor doses a patient with a large amount of aspirin, can be with
While replenishing vitamins C.On the one hand, aspirin can suppress with the acceptor on vitamin C competition leucocyte film
Leucocyte improves plasma vitamin C content ascorbic intake, and ascorbic excretion also increases in urine
Plus；On the other hand, vitamin C can accelerate the absorption of aspirin, comparatively fast reach treatment concentration, so as to accelerate
Aspirin plays a role.
Additionally, enteric coating technology can not only avoid medicine to the intense stimulus of gastric mucosa, improve medicine and cause
The stomach adverse reaction such as Nausea and vomiting, while concentration of the medicine in small intestine can also be improved, improve medicine
Absorb.
At present, the existing aspirin of in the market and vitamin C compound preparation often occur free salicylic acid it is exceeded and
Cause stability poor.Accordingly, it would be desirable to improve, aspirin and vitamin C compound preparation stability are improved, protected
Demonstrate,prove the security of clinical application.
The content of the invention
The technical problems to be solved by the invention are to overcome above-mentioned weak point, and research and design has preferably steady
It is qualitative, the good aspirin of oral absorption and vitamin C compound preparation and its preparation.
The invention provides compound enteric-coated of a kind of aspirin and vitamin C.
The structure of aspirin of the present invention and compound enteric-coated of vitamin C is followed successively by Ah Si from inside to outside
Woods and vitamin C compound label, spacer layer coating and enteric layer are coated.
The label of aspirin of the present invention and compound enteric-coated of vitamin C is by the Ah Si as active component
Woods and vitamin C are constituted with excipient.
Described active constituents of medicine is the aspirin and 10-40% vitamin Cs of 20%-60% by percentage by weight
Composition.The content that active component accounts for label is 48%~67%.
Described excipient includes filler, disintegrant, antioxidant, glidant and lubricant.
Specifically, the label of aspirin of the present invention and compound enteric-coated of vitamin C is by following weight percent
Proportioning into being grouped into：Aspirin 20~60%, vitamin C 10~40%, filler 10~50%, disintegrant
5~30%, adhesive 0.5%~2%, antioxidant, glidant 0%~2% and lubricant 0.2~2% and insolated layer materials
1.0%~5.0%.
Preferably, the label of aspirin of the present invention and compound enteric-coated of vitamin C is by following weight percent
Proportioning into being grouped into：Aspirin 40%, vitamin 24%, microcrystalline cellulose 12%, pregelatinized starch 11%,
Sodium carboxymethyl starch 7%, PVP 1%, Macrogol 6000 4%, sodium stearyl fumarate 1%.
In excipient of the present invention, the filler be selected from microcrystalline cellulose, pregelatinized starch, lactose,
One or more in mannitol, sorbierite or maltitol of mixture.
The disintegrant is selected from low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, Ac-Di-Sol
Or the mixture of one or more in PVPP.
Described adhesive is PVP.
The antioxidant is selected from one kind or their mixture in citric acid or tartaric acid.
Mixture of the glidant selected from one or more in silica or Macrogol 6000.
The lubricant is selected from one kind or their mixture in stearic acid or sodium stearyl fumarate.
The insolated layer materials of aspirin of the present invention and compound enteric-coated of vitamin C are fine hydroxypropyl methyl
Dimension element.
The enteric layer material of aspirin of the present invention and compound enteric-coated of vitamin C be methacrylic acid with
The copolymer of ethyl acrylate.
It is a further object of the present invention to provide the aspirin and vitamin C the preparation side of compound enteric-coated
Method.
The method comprises the following steps：
(1) label is prepared：
By aspirin, vitamin C, filler, adhesive, antioxidant, disintegrant, glidant, lubrication
Compressing tablet is carried out after agent is well mixed；Or
After aspirin, vitamin C, filler, adhesive, antioxidant are carried out into dry granulation, add
Compressing tablet is carried out after disintegrant, glidant, mix lubricant are uniform, label is made；
(2) spacer layer coating：Label carries out spacer layer coating；The coating parameter：Temperature of charge is 35 DEG C
~45 DEG C；Air intake flow：300m3/h；Pot rotating speed：10rpm；
(3) enteric layer is coated：Label separation layer outer surface carries out enteric layer coating again；The coating parameter：Control
Temperature of charge processed is at 30~40 DEG C；Air intake flow：300m3/h；Pot rotating speed：10rpm.
The insolated layer materials of aspirin of the present invention and compound enteric-coated of vitamin C are fine hydroxypropyl methyl
Dimension element.Spacer layer coating weightening 1.0%~5.0%.
The enteric layer material of aspirin of the present invention and compound enteric-coated of vitamin C be methacrylic acid with
The copolymer of ethyl acrylate.Enteric layer coating weight gain 5.0%-15.0%.
Aspirin and the compound enteric-coated plate shape of vitamin C prepared by the present invention is oval or cylinder.
Specification is aspirin 400mg and vitamin C 240mg, and the thickness of tablet is 5.5mm~8.0mm, firmly
It is 100N~180N to spend.
The aspirin and compound enteric-coated of vitamin C of present invention preparation are through Dissolution Rate Testing：
Aspirin and compound enteric-coated of vitamin C are checked 2 hours, every in 0.1mol/L hydrochloric acid solutions
Without crack, disintegration or ruckbildung, accumulation stripping quantity is less than 5.0%；Taken out after by tablet, washed with water
After washing, detection in phosphate buffer (pH 6.8) is put, the accumulation stripping quantity of enteric coatel tablets is more than 70.0% within 45 minutes.
Experiment explanation Tablets have significant enteric feature, in 0.1M hydrochloric acid solutions, in 2 hours almost
There is no medicine to disengage, in phosphate buffer, dissolution in 45 minutes up to more than 70%, so as to avoid medicine
To irritating and influence of the external environment to medicine for stomach.
Agents useful for same of the present invention and supplementary material are commercially available.
The beneficial effect of aspirin of the present invention and compound enteric-coated of vitamin C：
1) after aspirin provided by the present invention and vitamin C enteric coatel tablets are oral, do not released in UGI
Put but positioned in small intestine site and discharged, improve it in small intestine site drug concentration and bioavilability, while
Avoid the pessimal stimulation to stomach, safety and reliability.
2) because aspirin and vitamin C are to moist lability, the present invention uses dry-mixed/dry-mixed vertical compression technique,
Moisture is avoided on aspirin and ascorbic influence.
3) because aspirin in some auxiliary materials such as：In the presence of talcum powder, magnesium stearate etc., it is easier to
Generation hydrolysis, produces accessory substance salicylic acid, and the present invention avoids using these auxiliary materials, auxiliary material is carried out sternly
Diagrid is selected.As a result product of the present invention shows that free salicylic acid is far below standard through June accelerated stability.
4) product dissolution rate of the present invention is fast.In 0.1mol/L hydrochloric acid 2 hours almost without release,
Dissolution in 45 minutes is close to very in PH6.8 phosphate buffers.Tablet medicine content difference is small.
5) compound enteric-coated tablet quality stabilization of the invention, can avoid light, air, moisture etc. from influenceing it.
Shown through 6 months accelerated tests：Compared with 0 month, aspirin content only declines 0.4%, vitamin C
Content declines 0.5%, and relevant material merely add 0.6%, far superior to standard, and be convenient for carrying, transport.
6) Tablets facilitate clinical staff, the medication beneficial to patient, there is stronger clinic
Practicality.
Agents useful for same of the present invention and supplementary material are commercially available, aspirin and vitamin C that the present invention is provided
Compound enteric-coated piece preparation method is simple and easy to apply, is suitable to industrialized production, there is larger application value.
Specific embodiment
The present invention is further illustrated below by the mode of embodiment, but is not therefore limited the present invention to described
Scope of embodiments among.
Following examples agents useful for same and supplementary material are commercially available.
Embodiment 1：
The compound enteric-coated slice prescription of aspirin and vitamin C in 1.1 the present embodiment is as shown in table 1.
Table 1：The aspirin vitamin C enteric slice prescription (making 1000 altogether) of embodiment 1
Table 2：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 1
1.2 by the aspirin of above-mentioned formula, vitamin C, pregelatinized starch, sorbierite, PVP, friendship
Connection polyvinylpyrrolidone, silica cross 40 mesh stainless steel mesh, and mix equal using 5L cone-type mixers
It is even, add during stearic acid puts 5L cone-type mixers and be well mixed, pack, granule content (95%~105%) to be detected
Compressing tablet, uses sub- power ZP-7 tabletting machines, piece weight 1g/ pieces afterwards.Spacer layer coating (thing is carried out after compressing tablet
35~45 DEG C of material temperature degree；Air intake flow：300m3/h；Pot rotating speed：10rpm；Coating material：3% hydroxypropyl first
The aqueous solution of base cellulose (HPMC)：The HPMC of 15g is stirred to clarify in being added to 485g water)；Enteric
Layer is coated (30~40 DEG C of temperature of charge；Air intake flow：300m3/h；Pot rotating speed：10rpm) coating material：
(100g30% methacrylic acids and the ethyl acrylate copolymer aqueous solution (Utech L30D55) are added to 200g
Stirred in water) spacer layer coating weightening 1.5%, enteric layer coating weight gain 7.9%.
1.3 testing results are as shown in table 3 below：
Table 3：40 DEG C of embodiment 1, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 100.3% of 0 month
Drop to the 98.3% of June, Vitamin C content drops to the 99% of June from the 100% of 0 month；Free bigcatkin willow
Acid rises to the 1.24% of June from the 0.31% of 0 month, dissolution rate from 0 month when aspirin dissolution in 45 minutes
98.4%, vitamin C dissolution 98.9%, aspirin dissolution 96.6% in 45 minutes when dropping to June, dimension life
Plain C dissolutions 97.5%.
Embodiment 2：
Aspirin vitamin C enteric slice prescription in 2.1 the present embodiment is as shown in table 4.
Table 4：The compound enteric-coated slice prescription of aspirin and vitamin C (making 1000 altogether) of embodiment 2
Table 5：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 2
2.2 by the aspirin of above-mentioned formula, vitamin C, microcrystalline cellulose, mannitol, PVP, friendship
Connection sodium carboxymethylcellulose, silica cross 40 mesh stainless steel mesh, and mix equal using 5L cone-type mixers
It is even, add during stearic acid puts 5L cone-type mixers and be well mixed, pack, granule content (95%~105%) to be detected
Compressing tablet, separation layer (35~45 DEG C of temperature of charge is carried out using sub- power ZP-7 tabletting machines, after compressing tablet successively afterwards；
Air intake flow：300m3/h；Pot rotating speed：10rpm), enteric layer (30~40 DEG C of temperature of charge；Air intake flow：
300m3/h；Pot rotating speed：10rpm) it is coated.Spacer layer coating weightening 1.5%, enteric layer coating weight gain 7.9%.
2.3 testing results are as shown in table 6 below：
Table 6：40 DEG C of embodiment 2, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 100.6% of 0 month
Drop to the 97.6% of June, Vitamin C content drops to the 99.1% of June from the 100.2% of 0 month；It is free
Salicylic acid rises to the 1.48% of June from the 0.33% of 0 month, dissolution rate from 0 month when 45 minutes aspirin it is molten
Go out 98.9%, vitamin C dissolution 98.1%, aspirin dissolution 94.3% in 45 minutes when dropping to June, dimension
Raw element C dissolutions 97.1%.
Embodiment 3：
The compound enteric-coated slice prescription of aspirin and vitamin C in 3.1 the present embodiment is as shown in table 7.
Table 7：The compound enteric-coated slice prescription of aspirin and vitamin C (making 1000 altogether) of embodiment 3
Table 8：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 3
3.2 by the aspirin of above-mentioned formula, vitamin C, microcrystalline cellulose, sorbierite, PVP, friendship
Connection polyvinylpyrrolidone, citric acid cross 30 mesh stainless steel mesh, and are well mixed using 5L cone-type mixers,
Then dry granulation is carried out using GL-25 dry granulating machines；Again by dry particl, PVPP,
Silica crosses 40 mesh stainless steel mesh, reuses 5L cone-type mixers and is well mixed, and adds stearic acid and puts
It is well mixed in 5L cone-type mixers, pack, granule content (95%~105%) to be detected compressing tablet afterwards is used
Sub- power ZP-7 tabletting machines, carry out separation layer (35~45 DEG C of temperature of charge successively after compressing tablet；Air intake flow：
300m3/h；Pot rotating speed：10rpm), enteric layer (30~40 DEG C of temperature of charge；Air intake flow：300m3/h；
Pot rotating speed：10rpm) it is coated.Spacer layer coating weightening 1.5%, enteric layer coating weight gain 7.9%.
3.3 testing results are as shown in table 9 below：
Table 9：40 DEG C of embodiment 3, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 99.7% of 0 month
Drop to the 98.4% of June, Vitamin C content drops to the 99.4% of June from the 100.7% of 0 month；It is free
Salicylic acid rises to the 1.04% of June from the 0.24% of 0 month, dissolution rate from 0 month when 45 minutes aspirin it is molten
Go out 98.4%, vitamin C dissolution 98.3%, aspirin dissolution 97% in 45 minutes when dropping to June, dimension life
Plain C dissolutions 97.1%.
Embodiment 4：
The compound enteric-coated slice prescription of aspirin and vitamin C in 4.1 the present embodiment is as shown in table 10.
Table 10：The compound enteric-coated slice prescription of aspirin and vitamin C (making 1000 altogether) of embodiment 4
Table 11：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 4
4.2 by the aspirin of above-mentioned prescription, vitamin C, pregelatinized starch, PVP, crosslinked polyethylene
Pyrrolidones, silica cross 40 mesh stainless steel mesh, and are well mixed using 5L cone-type mixers, then add
Enter during sodium stearyl fumarate puts 5L cone-type mixers and be well mixed, pack, granule content (95%~105%) to be detected
Compressing tablet, separation layer (35~45 DEG C of temperature of charge is carried out using sub- power ZP-7 tabletting machines, after compressing tablet successively afterwards；
Air intake flow：300m3/h；Pot rotating speed：10rpm), enteric layer (30~40 DEG C of temperature of charge；Air intake flow：
300m3/h；Pot rotating speed：10rpm) it is coated.Spacer layer coating weightening 1.5%, enteric layer coating weight gain 7.9%.
4.3 testing results are as shown in table 12 below：
Table 12：40 DEG C of embodiment 4, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 100.3% of 0 month
Drop to the 99% of June, Vitamin C content drops to the 99.1% of June from the 100.1% of 0 month；Free water
Poplar acid rises to the 1.1% of June from the 0.3% of 0 month, dissolution rate from 0 month when aspirin dissolution in 45 minutes
98.1%, vitamin C dissolution 98.0%, aspirin dissolution 95.6% in 45 minutes when dropping to June, dimension life
Plain C dissolutions 96.4%.
Embodiment 5：
The compound enteric-coated slice prescription of aspirin and vitamin C in 5.1 the present embodiment is as shown in table 13.
The aspirin and the compound enteric-coated slice prescription of vitamin C (making 1000 altogether) of the embodiment 5 of table 13 (make 1000 altogether
Piece)
Table 14：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 5
5.2 by the aspirin of above-mentioned formula, vitamin C, lactose, sorbierite, PVP, low substitution hydroxyl
Propyl cellulose crosses 30 mesh stainless steel mesh, and is well mixed using 5L cone-type mixers, then uses GL-25
Dry granulating machine carries out dry granulation；Again by dry particl, low-substituted hydroxypropyl cellulose, Macrogol 6000
40 mesh stainless steel mesh are crossed, 5L cone-type mixers is reused and is well mixed, added stearic acid and put 5L tapers
It is well mixed in mixer, pack, granule content (95%~105%) to be detected compressing tablet afterwards uses sub- power ZP-7
Tabletting machine, carries out separation layer (35~45 DEG C of temperature of charge successively after compressing tablet；Air intake flow：300m3/h；
Pot rotating speed：10rpm), enteric layer (30~40 DEG C of temperature of charge；Air intake flow：300m3/h；Pot rotating speed：
10rpm) it is coated.Spacer layer coating weightening 1.5%, enteric layer coating weight gain 7.9%.
5.3 testing results are as shown in table 15 below：
Table 15：40 DEG C of embodiment 5, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 99.4% of 0 month
Drop to the 98.2% of June, Vitamin C content drops to the 98.1% of June from the 99.8% of 0 month；It is free
Salicylic acid rises to the 0.92% of June from the 0.25% of 0 month, dissolution rate from 0 month when 45 minutes aspirin it is molten
Go out 97.4%, vitamin C dissolution 98.3%, aspirin dissolution 96% in 45 minutes when dropping to June, dimension life
Plain C dissolutions 96.6%.
Embodiment 6：
Aspirin vitamin C enteric slice prescription in 6.1 the present embodiment is as shown in table 16.
Table 16：The aspirin vitamin C enteric slice prescription (making 1000 altogether) of embodiment 6
Table 17：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 6
6.2 by the aspirin of above-mentioned prescription, vitamin C, microcrystalline cellulose, pregelatinized starch, PVP,
Low-substituted hydroxypropyl cellulose, silica cross 40 mesh stainless steel mesh, and are mixed using 5L cone-type mixers
Uniformly, add during magnesium stearate puts 5L cone-type mixers and be well mixed, pack, granule content to be detected
(95%~105%) compressing tablet afterwards, using sub- power ZP-7 tabletting machines, carries out separation layer (thing successively after compressing tablet
35~45 DEG C of material temperature degree；Air intake flow：300m3/h；Pot rotating speed：10rpm), enteric layer (30~40 DEG C of temperature of charge；
Air intake flow：300m3/h；Pot rotating speed：10rpm) it is coated.Spacer layer coating weightening 1.5%, enteric layer bag
Clothing weightening 7.9%.
6.3 testing results are as shown in table 18 below：
Table 18：40 DEG C of embodiment 6, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 99.9% of 0 month
Drop to the 98.6% of June, Vitamin C content drops to the 98.7% of June from the 99.8% of 0 month；It is free
Salicylic acid rises to the 1.32% of June from the 0.3% of 0 month, dissolution rate from 0 month when 45 minutes aspirin it is molten
Go out 98.3%, vitamin C dissolution 98.1%, aspirin dissolution 95.4% in 45 minutes when dropping to June, dimension
Raw element C dissolutions 96.3%.
Embodiment 7：
The compound enteric-coated slice prescription of aspirin and vitamin C in 7.1 the present embodiment is as shown in table 19.
The aspirin vitamin C enteric slice prescription (making 1000 altogether) of the embodiment 7 of table 19
Table 20：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 7
7.2 by the aspirin of above-mentioned formula, vitamin C, microcrystalline cellulose, maltitol, PVP,
Sodium carboxymethyl starch, tartaric acid cross 30 mesh stainless steel mesh, and are well mixed using 5L cone-type mixers, so
Afterwards dry granulation is carried out using GL-25 dry granulating machines；Dry particl, Macrogol 6000 are crossed into 40 mesh not again
Rust steel screen cloth, reuses 5L cone-type mixers and is well mixed, and adds sodium stearyl fumarate and puts 5L tapers mixing
It is well mixed in machine, pack, granule content (95%~105%) to be detected compressing tablet afterwards uses sub- power ZP-7 compressing tablets
Machine compressing tablet, carries out separation layer (35~45 DEG C of temperature of charge successively after compressing tablet；Air intake flow：300m3/h；Pot
Rotating speed：10rpm), enteric layer (30~40 DEG C of temperature of charge；Air intake flow：300m3/h；Pot rotating speed：10rpm)
It is coated.Spacer layer coating weightening 1.5%, enteric layer coating weight gain 7.9%.
7.3 testing results are as shown in table 21 below：
Table 21：40 DEG C of embodiment 7, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 99.9% of 0 month
Drop to the 98.3% of June, Vitamin C content drops to the 97.8% of June from the 99.8% of 0 month；It is free
Salicylic acid rises to the 0.9% of June from the 0.2% of 0 month, dissolution rate from 0 month when aspirin dissolution in 45 minutes
97.8%, vitamin C dissolution 97.6%, aspirin dissolution 96.6% in 45 minutes when dropping to June, dimension life
Plain C dissolutions 96.0%.
Coating tablet embodiment 8：
The compound enteric-coated slice prescription of aspirin and vitamin C in 8.1 the present embodiment is as shown in table 22.
The aspirin and the compound enteric-coated slice prescription of vitamin C (making 1000 altogether) of the embodiment 8 of table 22
Table 23：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 8
8.2 by the aspirin of above-mentioned formula, vitamin C, microcrystalline cellulose, sorbierite, cross-linked carboxymethyl
Sodium cellulosate, silica cross 40 mesh stainless steel mesh, and are well mixed using 5L cone-type mixers, then add
Enter during stearic acid puts 5L cone-type mixers and be well mixed, pack, after granule content (95%~105%) to be detected
Compressing tablet, separation layer (35~45 DEG C of temperature of charge is carried out using sub- power ZP-7 tabletting machines, after compressing tablet successively；
Air intake flow：300m3/h；Pot rotating speed：10rpm), enteric layer (30~40 DEG C of temperature of charge；Air intake flow：
300m3/h；Pot rotating speed：10rpm) it is coated.Spacer layer coating weightening 1.5%, enteric layer coating weight gain 7.9%.
8.3 testing results are as shown in table 24 below：
Table 24：40 DEG C of embodiment 8, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 99.7% of 0 month
Drop to the 98.3% of June, Vitamin C content drops to the 98.0% of June from the 99.9% of 0 month；It is free
Salicylic acid rises to the 1.43% of June from the 0.32% of 0 month, dissolution rate from 0 month when 45 minutes aspirin it is molten
Go out 98.1%, vitamin C dissolution 97.6%, aspirin dissolution 95.3% in 45 minutes when dropping to June, dimension
Raw element C dissolutions 96.0%.
Embodiment 9：
The compound enteric-coated slice prescription of aspirin and vitamin C in 9.1 the present embodiment is as shown in Table 25.
The aspirin and the compound enteric-coated slice prescription of vitamin C (making 1000 altogether) of the embodiment 9 of table 25
Table 26：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 9
9.2 by the aspirin vitamin C of above-mentioned prescription, microcrystalline cellulose, pregelatinized starch, PVP,
Sodium carboxymethyl starch, Macrogol 6000 cross 40 mesh stainless steel mesh, and are mixed using 5L cone-type mixers
Uniformly, add during stearic acid puts 5L cone-type mixers and be well mixed, pack, granule content to be detected
(95%~105%) compressing tablet afterwards, using sub- power ZP-7 tabletting machines, carries out separation layer (thing successively after compressing tablet
35~45 DEG C of material temperature degree；Air intake flow：300m3/h；Pot rotating speed：10rpm), enteric layer (30~40 DEG C of temperature of charge；
Air intake flow：300m3/h；Pot rotating speed：10rpm) it is coated.Spacer layer coating weightening 1.5%, enteric layer bag
Clothing weightening 7.9%.
9.3 testing results are as shown in table 27 below：
Table 27：40 DEG C of embodiment 9, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 100.3% of 0 month
Drop to the 99.4% of June, Vitamin C content drops to the 99.0% of June from the 100.0% of 0 month；It is free
Salicylic acid rises to the 0.89% of June from the 0.24% of 0 month, dissolution rate from 0 month when 45 minutes aspirin it is molten
Go out 98.8%, vitamin C dissolution 98.7%, aspirin dissolution 97.1% in 45 minutes when dropping to June, dimension
Raw element C dissolutions 97.1%.
Embodiment 10：
The compound enteric-coated slice prescription of aspirin and vitamin C in 10.1 the present embodiment is as shown in table 28.
The aspirin and the compound enteric-coated slice prescription of vitamin C (making 1000 altogether) of the embodiment 10 of table 28
Table 29：The aspirin vitamin C enteric coatel tablets coated formula (making 1000 altogether) of embodiment 10
10.2 by the aspirin vitamin C of above-mentioned formula, microcrystalline cellulose, pregelatinized starch, PVP,
Sodium carboxymethyl starch, Macrogol 6000 cross 40 mesh stainless steel mesh, and are mixed using 5L cone-type mixers
Uniformly, add during sodium stearyl fumarate puts 5L cone-type mixers and be well mixed, pack, particle to be detected contains
(95%~105%) compressing tablet afterwards is measured, using sub- power ZP-7 tabletting machines, separation layer (thing is carried out after compressing tablet successively
35~45 DEG C of material temperature degree；Air intake flow：300m3/h；Pot rotating speed：10rpm), enteric layer (30~40 DEG C of temperature of charge；
Air intake flow：300m3/h；Pot rotating speed：10rpm) it is coated.Spacer layer coating weightening 1.5%, enteric layer bag
Clothing weightening 7.9%.
10.3 testing results are as shown in table 30 below：
Table 30：40 DEG C of embodiment 10, six months stability data tables of RH75%
Result shows：By 40 DEG C of 6 months, RH75% accelerated tests, aspirin content is from the 100.4% of 0 month
Drop to the 100.0% of June, Vitamin C content drops to the 99.8% of June from the 100.3% of 0 month；Trip
Rise to the 0.87% of June from the 0.21% of 0 month from salicylic acid, dissolution rate from 0 month when 45 minutes aspirin
Dissolution 98.9%, vitamin C dissolution 98.9%, aspirin dissolution 98.0% in 45 minutes when dropping to June,
Vitamin C dissolution 97.8%.
Claims (10)
1. aspirin and compound enteric-coated of vitamin C, it is characterised in that the aspirin and vitamin
The structure that C is compound enteric-coated is followed successively by aspirin and vitamin C compound label, spacer layer coating from inside to outside
It is coated with enteric layer.
2. aspirin and compound enteric-coated of vitamin C according to claim 1, it is characterised in that institute
The label of aspirin and vitamin C Compound Tablet is stated by as the aspirin and vitamin C of active component and tax
Shape agent is constituted.
3. aspirin according to claim 1 or claim 2 and compound enteric-coated of vitamin C, it is characterised in that
Described active constituents of medicine is by percentage by weight for the aspirin and 80-40% vitamin Cs of 20%-60% are constituted；
The content that the active component accounts for label is 48%~67%.
4. aspirin and compound enteric-coated of vitamin C according to claim 2, it is characterised in that institute
The excipient stated includes filler, disintegrant, antioxidant, glidant and lubricant.
5. aspirin and compound enteric-coated of vitamin C according to claim 1, it is characterised in that institute
State the label of aspirin and compound enteric-coated of vitamin C by following weight percent match into being grouped into：A Si
Woods 20~60%, vitamin C 10~40%, filler 10~50%, disintegrant 5~30%, adhesive 0.5%~2%,
Antioxidant, glidant 0%~2% and lubricant 0.2~2% and insolated layer materials 1.0%~5.0%.
6. aspirin and compound enteric-coated of vitamin C according to claim 5, it is characterised in that institute
State the label of aspirin and compound enteric-coated of vitamin C by following weight percent match into being grouped into：A Si
Woods 40%, vitamin 24%, microcrystalline cellulose 12%, pregelatinized starch 11%, sodium carboxymethyl starch 7%,
PVP 1%, Macrogol 6000 4%, sodium stearyl fumarate 1%.
7. aspirin and compound enteric-coated of vitamin C according to claim 2, it is characterised in that institute
Filler is stated to be selected from microcrystalline cellulose, pregelatinized starch, lactose, mannitol, sorbierite or maltitol
One or more of mixture；The disintegrant is selected from low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, friendship
One or more of mixture in connection sodium carboxymethylcellulose or PVPP；Described adhesive
It is PVP；The antioxidant is selected from one kind or their mixture in citric acid or tartaric acid；It is described to help stream
Mixture of the agent selected from one or more in silica or Macrogol 6000；The lubricant is selected from hard
One kind or their mixture in resin acid or sodium stearyl fumarate.
8. aspirin and compound enteric-coated of vitamin C according to claim 1, it is characterised in that institute
The insolated layer materials for stating aspirin and compound enteric-coated of vitamin C are hydroxypropyl methyl cellulose；The enteric
Layer material is the copolymer of methacrylic acid and ethyl acrylate.
9. as described in claim 1,5 or 6 aspirin and compound enteric-coated of vitamin C preparation method,
Characterized in that, the method comprises the following steps：
(1) label is prepared：
By aspirin, vitamin C, filler, adhesive, antioxidant, disintegrant, glidant, lubrication
Compressing tablet is carried out after agent is well mixed；
(2) spacer layer coating：Label carries out spacer layer coating；The insolated layer materials are hydroxypropyl methyl fiber
Element；Coating parameter：Temperature of charge is 35 DEG C~45 DEG C；Air intake flow：300m3/h；Pot rotating speed：10rpm；
(3) enteric layer is coated：Label separation layer outer surface carries out enteric layer coating again；The enteric layer material is
The copolymer of methacrylic acid and ethyl acrylate；Coating parameter：Control material temperature is at 30~40 DEG C；Air intake
Flow：300m3/h；Pot rotating speed：10rpm.
10. the preparation method of aspirin and compound enteric-coated of vitamin C according to claim 9, it is special
Levy and be, the step (1) prepares label：By aspirin, vitamin C, filler, adhesive,
After antioxidant carries out dry granulation, add disintegrant, glidant, mix lubricant it is uniform after carry out compressing tablet.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111436615A (en) * | 2020-03-29 | 2020-07-24 | 耶赛明(南通)保健有限公司 | Compound vitamin C health food and preparation method thereof |
| CN111529501A (en) * | 2020-06-30 | 2020-08-14 | 南京白敬宇制药有限责任公司 | Preparation method of aspirin vitamin C dispersible tablet |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1679592A (en) * | 2005-01-11 | 2005-10-12 | 石家庄制药集团欧意药业有限公司 | Antipyretic and analgetic aspirin enteric-coated preparation and production thereof |
| CN103316022A (en) * | 2013-06-09 | 2013-09-25 | 广东医学院 | Pharmaceutical composition composed of aspirin and vitamin C and used for preventing and treating lung injury caused by smoking |
| CN104800183A (en) * | 2015-04-14 | 2015-07-29 | 南京多宝生物科技有限公司 | Aspirin enteric-coated tablet as well as preparation method and application thereof |
-
2015
- 2015-12-15 CN CN201510934905.0A patent/CN106880639A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1679592A (en) * | 2005-01-11 | 2005-10-12 | 石家庄制药集团欧意药业有限公司 | Antipyretic and analgetic aspirin enteric-coated preparation and production thereof |
| CN103316022A (en) * | 2013-06-09 | 2013-09-25 | 广东医学院 | Pharmaceutical composition composed of aspirin and vitamin C and used for preventing and treating lung injury caused by smoking |
| CN104800183A (en) * | 2015-04-14 | 2015-07-29 | 南京多宝生物科技有限公司 | Aspirin enteric-coated tablet as well as preparation method and application thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111436615A (en) * | 2020-03-29 | 2020-07-24 | 耶赛明(南通)保健有限公司 | Compound vitamin C health food and preparation method thereof |
| CN111529501A (en) * | 2020-06-30 | 2020-08-14 | 南京白敬宇制药有限责任公司 | Preparation method of aspirin vitamin C dispersible tablet |
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