CN1562013A - Nisoldipine oral disintegration tablet for treating hypertension and preparing method - Google Patents
Nisoldipine oral disintegration tablet for treating hypertension and preparing method Download PDFInfo
- Publication number
- CN1562013A CN1562013A CN 200410032067 CN200410032067A CN1562013A CN 1562013 A CN1562013 A CN 1562013A CN 200410032067 CN200410032067 CN 200410032067 CN 200410032067 A CN200410032067 A CN 200410032067A CN 1562013 A CN1562013 A CN 1562013A
- Authority
- CN
- China
- Prior art keywords
- oral cavity
- agent
- nisoldipine
- disintegration tablet
- adjuvant
- Prior art date
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- Pending
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- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 229960000227 nisoldipine Drugs 0.000 title claims abstract description 30
- 206010020772 Hypertension Diseases 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 5
- 210000000214 mouth Anatomy 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 20
- 239000002671 adjuvant Substances 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
- 239000000796 flavoring agent Substances 0.000 claims description 15
- 230000002378 acidificating effect Effects 0.000 claims description 13
- 239000004088 foaming agent Substances 0.000 claims description 13
- 235000013355 food flavoring agent Nutrition 0.000 claims description 13
- 239000008187 granular material Substances 0.000 claims description 13
- 239000011230 binding agent Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 108010011485 Aspartame Proteins 0.000 claims description 7
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 7
- 239000000605 aspartame Substances 0.000 claims description 7
- 235000010357 aspartame Nutrition 0.000 claims description 7
- 229960003438 aspartame Drugs 0.000 claims description 7
- 239000000314 lubricant Substances 0.000 claims description 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 7
- -1 isobutyl methyl ester C Chemical compound 0.000 claims description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 5
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- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
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- 235000019698 starch Nutrition 0.000 claims description 4
- 229940013618 stevioside Drugs 0.000 claims description 4
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 4
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- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- 239000011575 calcium Substances 0.000 claims description 3
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- 239000000126 substance Substances 0.000 claims description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 229920001817 Agar Polymers 0.000 claims description 2
- 241000416162 Astragalus gummifer Species 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 229920002261 Corn starch Polymers 0.000 claims description 2
- YTBSYETUWUMLBZ-UHFFFAOYSA-N D-Erythrose Natural products OCC(O)C(O)C=O YTBSYETUWUMLBZ-UHFFFAOYSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- YTBSYETUWUMLBZ-IUYQGCFVSA-N D-erythrose Chemical compound OC[C@@H](O)[C@@H](O)C=O YTBSYETUWUMLBZ-IUYQGCFVSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 2
- 206010056474 Erythrosis Diseases 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- 241001597008 Nomeidae Species 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 229920001615 Tragacanth Polymers 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 claims description 2
- 239000008272 agar Substances 0.000 claims description 2
- 229940023476 agar Drugs 0.000 claims description 2
- 235000010419 agar Nutrition 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 229950008138 carmellose Drugs 0.000 claims description 2
- 239000008120 corn starch Substances 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 230000001631 hypertensive effect Effects 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 229940041616 menthol Drugs 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
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- 206010007559 Cardiac failure congestive Diseases 0.000 abstract description 2
- 206010019280 Heart failures Diseases 0.000 abstract description 2
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- 239000007884 disintegrant Substances 0.000 abstract 1
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
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- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
An oral disintegrating tablet for nisoldipine for treating coronary heart disease, hypertension, ischemic heart disease and congestive heart failure is prepared from nisoldipine, souring agnet, excipient and disintegrant.
Description
Technical field
What the present invention relates to is pharmaceutical preparation in the field of medicaments, specifically a kind of nisoldipine oral cavity disintegration tablet that is used for the treatment of hypertension and preparation method thereof.
Technical background
Nisoldipine is a strongest current calcium antagonist, has optionally coronary artery dilator effect, than the strong 4-10 of nifedipine doubly.Pharmaceutical research shows: the voltage that nisoldipine suppresses smooth muscle relies on strides the film calcium ionic current, and vascular smooth muscle is had the high selectivity effect, owing to blood vessel dilating improves oxygen supply, reduces afterload and reduces oxygen and consume.Nisoldipine is oral almost completely to be absorbed, and reaches blood medicine peak value after the oral absorption in 1 hour.Medicine half-life (t in vivo
1/2) variance is bigger between patient, the oral t of single agent
1/2Be 11.4h.Treating hypertensive consumption is: oral 1 time of every day, each 5-10mg; Treating anginal consumption is: oral 10mg, is adjusted to 20-40mg by symptom, every day 1 time gradually at beginning every day 1 time.
Hypertension is common cardiovascular diseases, and except that the part patient can find the reason, majority is a constitutional, must carry out the blood pressure lowering treatment for a long time.Hypertension is higher at our national sickness rate, and particularly person in middle and old age group, sickness rate has the patient crowd up to about 100,000,000 up to 14%, but also in further raising.But, cause the critical illness of the serious harm people life and healths such as apoplexy that cause because of hypertension to take place because patient often can not adhere to long-term prescription.Can not adhere to a very big reason of taking medicine be because work, life busy and nervous forget take medicine, or need use water delivery service when taking medicine, inconvenience, and be unwilling to take, particularly gerontal patient group.Developing a kind of Shi Buxu of taking medicine water delivery service thus, is highly significant and can directly tablet be placed on the oral cavity disintegration tablet that can reach the treatment disease in the oral cavity at any time, and this tablet will bring administering mode very easily to the patient.
Nisoldipine oral cavity disintegration tablet of the present invention, it is a kind of tablet that need not use water delivery service, the patient only needs tablet is put into the oral cavity when taking, only tablet gets final product whole disintegrates or dissolves in 30 seconds, along with excretory saliva in the oral cavity is increased, people's normal swallowing act can be sent medicine into gastric, and medicine can absorb rapidly, improved drug bioavailability widely, made medicine bring into play drug effect in vivo rapidly.It can also improve the compliance that the patient takes medicine greatly, and this point is particularly suitable for old and serious symptom patient, is a kind of administration medicine novel formulation very easily.The oral cavity disintegration tablet medicine of exploitation is more both at home and abroad in recent years, to become a kind of developing direction of oral administered dosage form, the oral cavity disintegration tablet of having developed at present can't satisfy various cause of disease patients' demand clinically, and their preparation method and clinical use respectively have quality, with " freeze-drying " is that the oral cavity disintegration tablet of representative is fastest at intraoral disintegration, but the intensity difference of slice, thin piece, tablet is broken easily, incompatibility industrialized great production and patient are inconvenient to use, and also do not satisfy the demand in market; The preparation method of other oral cavity disintegration tablets has " subliming by heating method " and direct compression process, though they have overcome the shortcoming of the intensity difference of tablet, but it is most when the patient uses, feel to have not sand type and unacceptable uncomfortable sensation or disintegration time long in the oral cavity, particularly but the oral cavity disintegration tablet of subliming by heating method preparation also might residual sublimate, and those are to be unfavorable for healthy chemical substance; " direct compression process " in preparation process, the poor compressibility of tablet makes tablet outward appearance or tablet weight variation be not easy to reach the regulation of pharmacopeia to tablet, has limited the development of oral cavity disintegration tablet.Or the like these all need more the drug preparation technique of science and the support of theory of medicine, this new pharmaceutical preparation can be developed rapidly and more extensively used.
Summary of the invention
The purpose of this invention is to provide a kind of nisoldipine oral cavity disintegration tablet and preparation method that is used for the treatment of hypertension, the patient only needs oral cavity disintegration tablet of the present invention is put into the oral cavity, need not to drink water, owing to contain acidic flavoring agent in the tablet, the salivation amount is increased, make that tablet was disintegratable or dissolving, along with swallowing act is sent medicine into gastric, brought into play drug effect rapidly in 30 seconds.
The object of the present invention is achieved like this: be used for the treatment of the nisoldipine oral cavity disintegration tablet of hypertension, form by principal agent and adjuvant, wherein:
(1) principal agent: nisoldipine
A. English name: Nisoldipine
B. chemical name: 1,4-dihydro-2,6-dimethyl-4-(2-Nitrobenzol)-3,5-dipicolinic acid isobutyl methyl ester
C. molecular formula: C
20H
24N
2O
6Molecular weight: 388.42
D. structural formula:
Contain principal agent 5-40mg in every.
(2) adjuvant: adjuvant is formed (in every weight) by three parts in the oral cavity disintegration tablet of the present invention:
Excipient: 10-500mg
Acidic flavoring agent: 0.001-100mg
Disintegrating agent: 2-200mg
In prescription, also can add a kind of in foaming agent or binding agent or the correctives or their mixture.
Foaming agent or binding agent or correctives are counted with every weight: foaming agent: 0-150mg, binding agent;
0-50mg, correctives: 0-50mg.
Described excipient is: a kind of in mannitol, lactose, sucrose, glucose, sorbitol, xylitol, the erythrose etc., or their mixture.
Described acidic flavoring agent is: a kind of in citric acid, tartaric acid, fumaric acid, the malic acid etc.
Described disintegrating agent is: a kind of in crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, microcrystalline Cellulose, Carmellose calcium, low-substituted hydroxypropyl cellulose, corn starch sodium, the micropowder silica gel etc., or their mixture.
Described foaming agent is made up of acidic flavoring agent and sodium carbonate or sodium bicarbonate.
Described binding agent is: a kind of in polyvinylpyrrolidone, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, vinylpyrrolidone, arabic gum, Tragacanth, xanthan gum, sodium alginate, pectin, agar, water dispersible starch and the derivant thereof, or their mixture.
Described correctives is: a kind of in aspartame, aspartame, stevioside, protein sugar, saccharin sodium, Herba Menthae, menthol, the essence etc., or their mixture.
First kind of preparation method of the present invention is:
1, will carry out wet method system granule, drying behind principal agent, adjuvant (except the foaming agent) mix homogeneously;
2, the tabletting on tablet machine with dried granule and the even back of mix lubricant.
Also can be in lubricant joins dried granule with a kind of in foaming agent or binding agent or the correctives or their mixture, behind the mix homogeneously on tablet machine tabletting.
Second kind of preparation method of the present invention is:
To directly carry out tabletting behind principal agent and all the adjuvant mix homogeneously.
The present invention has following characteristics:
1. the present invention is a kind of oral cavity disintegration tablet that adopts certain preparation method to make with nisoldipine pharmaceutical compositions and the adjuvant that matches, the user puts into the oral cavity with tablet of the present invention, because the existence of acidic flavoring agent, stimulate the saliva of buccal cavity rapid release, in time less than 30 seconds kinds, can not feel the existence of tablet in the oral cavity, in the process of tablet disintegrate, allow the people feel to have a kind of cool and comfortable sense, and do not have the sensation of any discomfort, more there is not sand type and pasty state sensation.
Tablet of the present invention contribution clinically is light for the treatment constitutional, moderate hypertension disease and angina pectoris, does not need drug administration by injection, and oral administration and need not to drink water can reach clinical therapeutic efficacy, and is easy to use.The patient group that oral cavity disintegration tablet of the present invention mainly is suitable for clinically has: administration patient under the patient of water restriction, the psychosis of not being obedient to oral administration, the operate outside anhydrous condition in the patient of middle-older patient, critical illness patient, drinking-water dysphagia, the doctor's advice.Oral cavity disintegration tablet of the present invention is put into patient's oral cavity, tablet is complete disintegrate in 30 seconds, along with the behavior of swallowing is sent disintegrate or the medicine that dissolves into gastric and is absorbed by the body, or directly be absorbed, reach the purpose of treatment or disease preventing and treating at oral mucosa.
2. oral cavity disintegration tablet of the present invention has added a certain amount of acidic flavoring agent in prescription, the existence of this acidic flavoring agent can not make the oral cavity feel any uncomfortable sensation, it can stimulate the salivary gland in the human oral cavity to discharge the saliva of the nearly 1 times of amount in oral cavity at ordinary times at short notice, make the quick disintegrate of tablet in the oral cavity, this also is a key point of the present invention.The present invention is with provable this phenomenon of following result of the test:
At first suppress the oral cavity disintegration tablet base (T that some contain a certain amount of acidic flavoring agent by the prescription of design
1), and fill a prescription identical but do not contain the oral cavity disintegration tablet base (T of acidic flavoring agent
2) (two kinds of sheet bases all do not contain the medicine active ingredient), use for the test contrast.The experimenter participates in test equal morning on an empty stomach, everyone all gargles before the test, after 10 minutes, experimenter's seat posture, collect 5min saliva, saliva can not be swallowed during collection, all dehisce, slightly loll, allow the saliva nature flow into the scale test tube through funnel, 5min at the end all spits into test tube (but expectorant can not be spat into) with contained saliva in the oral cavity, and collection finishes, test tube is vertically inserted test tube rack, put 4 ℃ of natural sedimentations and eliminate foam 24h, press calibration record saliva amount, and measure pH value with precision test paper.Use T during test earlier
2The sheet base is tested, and finishes the back and carries out T at interval in 0.5 hour again
1The test of sheet base, the sheet base is put into the Sublingual, oral cavity and was picked up counting 5 minutes, and result of the test sees the following form:
Saliva of buccal cavity secretory volume result of the test table
(test number 10 people, the men and women half and half, age 22-38 year)
Tested number 123456789 10 X ± S PH
T
2Saliva amount (ml) 1.5 2.0 1.3 2.0 1.8 2.5 2.2 1.9 1.1 2.3 1.86 ± 0.24
PH
2 6.0 6.3 6.5 6.3 6.4 6.0 6.5 6.2 6.0 6.3 6.25±0.03
T
1Saliva amount (ml) 2.6 2.8 2.8 3.3 3.5 3.8 3.8 2.7 2.6 3.5 3.14 ± 0.16
PH
1 6.0 6.2 6.5 6.3 6.2 6.2 6.5 6.0 6.3 6.1 6.23±0.03
Obviously find to test T from result of the test
1Saliva amount greater than test T
2,, work as T in process of the test
1After putting into the subject oral cavity Sublingual, the experimenter feels that immediately saliva of buccal cavity increases sharply, but after 2 minutes, recovers former salivation state.This shows the effect that the oral cavity disintegration tablet that contains acidic flavoring agent has stimulates saliva of buccal cavity glandular secretion saliva.
Preparation method of the present invention is easy and simple to handle, feasible process, and made tablet meets the regulation of two appendix tablets of Chinese Pharmacopoeia version in 2000.By the oral cavity disintegration tablet steady quality that the present invention produces, cost is low, has better practicability.
The specific embodiment
Be described in further detail the present invention below in conjunction with embodiment, but should understand the scope that scope of the present invention is not limited only to these embodiment.
Embodiment 1
The name of an article: nisoldipine oral cavity disintegration tablet
Specification: 5mg/ sheet
Prescription 1: nisoldipine 5g
Lactose 65g
Crospolyvinylpyrrolidone (CPVP) 4g
Citric acid 0.5g
Aspartame 1g
Flavor powder 0.5g
Magnesium stearate 0.5g
Preparation method: with nisoldipine, lactose, crospolyvinylpyrrolidone, citric acid, aspartame mix homogeneously, water is made 20 order granules, put 60 ℃ of dry 4-6h, behind dried granule and magnesium stearate lubricant, flavor powder mix homogeneously, cross 18 mesh sieve granulate, compacting is 1000 on tablet machine.
Embodiment 2
The name of an article: nisoldipine oral cavity disintegration tablet
Specification: 10mg/ sheet
Prescription 2: nisoldipine 10g
Mannitol 100g
Cross-linking sodium carboxymethyl cellulose 10g
Tartaric acid 2g
Stevioside 1g
5% polyvinylpyrrolidone alcoholic solution is an amount of
Magnesium stearate 0.5g
Preparation method: at first take by weighing a certain amount of polyvinylpyrrolidone, become 5% (weight/volume, W/V) the polyvinylpyrrolidone alcoholic solution of concentration with the 30-90% dissolve with ethanol.Measure an amount of this solution again, add nisoldipine, stirring all is dissolved in the polyvinylpyrrolidone alcoholic solution medicine, adds tartaric acid, stevioside again, stirs.With mannitol, cross-linking sodium carboxymethyl cellulose mix homogeneously, cross 120 mesh sieves, the settled solution for preparing is added wherein, soft material is made in stirring, makes 20 order granules by wet method, puts 60 ℃ of dry 4h, sneak into magnesium stearate, cross 18 mesh sieve granulate, compacting is 1000 on tablet machine.
Embodiment 3
The name of an article: nisoldipine oral cavity disintegration tablet
Specification: 20mg/ sheet
Prescription 3: nisoldipine 20g
Mannitol 150g
Crospolyvinylpyrrolidone (CPVP) 6g
Cross-linking sodium carboxymethyl cellulose 8g
Citric acid 3g
Aspartame 0.2g
5% polyvinylpyrrolidone alcoholic solution is an amount of
Magnesium stearate 1g
Preparation method: directly carry out tabletting behind principal agent and all the adjuvant mix homogeneously.
Among embodiment 1, embodiment 2, the embodiment 3, all can in granule or mixed powder, add a kind of in an amount of essence or Herba Menthae or the foaming agent before the tabletting, or their mixture, make tablet produce a kind of gratifying sensation in the Orally disintegrating process.More than enumerate among three embodiment every principal agent nisoldipine 5mg, 10mg, three specifications of 20mg, when this product of preparation, every sheet is heavy variable, and only adjuvant increases or reduces.Other every embodiment method that contains principal agent 5-40mg is the same.
Product of the present invention can be used for ischemic heart desease, congestive heart failure and patients with hypertension, and is particularly suitable to the patient of coronary heart disease with hypertension.
Claims (8)
1. one kind is used for the treatment of hypertensive nisoldipine oral cavity disintegration tablet, it is characterized in that filling a prescription forming by principal agent and adjuvant, wherein:
(1) principal agent: nisoldipine
A. English name: Nisoldipine
B. chemical name: 1,4-dihydro-2,6-dimethyl-4-(2-Nitrobenzol)-3,5-dipicolinic acid isobutyl methyl ester
C. molecular formula: C
20H
24N
2O
6Molecular weight: 388.42
D. structural formula:
Contain principal agent 5-40mg in every.
(2) adjuvant: adjuvant is formed (in every weight) by three parts in the oral cavity disintegration tablet of the present invention:
Excipient: 10-500mg
Acidic flavoring agent: 0.001-100mg
Disintegrating agent: 2-200mg
2. oral cavity disintegration tablet as claimed in claim 1 is characterized in that: the excipient in the described adjuvant is: a kind of in mannitol, lactose, sucrose, glucose, sorbitol, xylitol, the erythrose etc., or their mixture; Acidic flavoring agent in the described adjuvant is: a kind of in citric acid, tartaric acid, fumaric acid, the malic acid etc. or their mixture; Disintegrating agent in the described adjuvant is: a kind of in crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, microcrystalline Cellulose, Carmellose calcium, low-substituted hydroxypropyl cellulose, corn starch sodium, the micropowder silica gel etc., or their mixture.
3. oral cavity disintegration tablet as claimed in claim 1, it is characterized in that: in prescription, also can add a kind of in foaming agent or binding agent or the correctives, or their mixture, foaming agent or binding agent or correctives consumption are counted with every weight: foaming agent: 0-150mg, binding agent: 0-50mg, correctives: 0-50mg.
4. oral cavity disintegration tablet as claimed in claim 3 is characterized in that: described foaming agent is made up of acidic flavoring agent and sodium carbonate or sodium bicarbonate; Described binding agent is: a kind of in polyvinylpyrrolidone, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, vinylpyrrolidone, arabic gum, Tragacanth, xanthan gum, sodium alginate, pectin, agar, water dispersible starch and the derivant thereof, or their mixture; Described correctives is: a kind of in aspartame, aspartame, stevioside, protein sugar, saccharin sodium, Herba Menthae, menthol, the essence etc. or their mixture.
5. the preparation method of oral cavity disintegration tablet as claimed in claim 1 is characterized in that:
(1) will carry out wet method system granule, drying behind medicine nisoldipine, the adjuvant mix homogeneously;
(2) more dried granule and mix lubricant are carried out tabletting after evenly.
6. the preparation method of oral cavity disintegration tablet as claimed in claim 1 is characterized in that: medicine nisoldipine, adjuvant, mix lubricant are directly carried out tabletting after evenly.
7. the preparation method of oral cavity disintegration tablet as claimed in claim 3 is characterized in that:
(1) will carry out wet method system granule, drying behind a kind of in medicine nisoldipine, adjuvant and binding agent or the correctives or their the mixture mix homogeneously;
(2) will carry out tabletting behind dried granule and lubricant, the foaming agent mix homogeneously.
8. the preparation method of oral cavity disintegration tablet as claimed in claim 3 is characterized in that: medicine nisoldipine, adjuvant, foaming agent, binding agent, correctives, mix lubricant are directly carried out tabletting after evenly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410032067 CN1562013A (en) | 2004-03-31 | 2004-03-31 | Nisoldipine oral disintegration tablet for treating hypertension and preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410032067 CN1562013A (en) | 2004-03-31 | 2004-03-31 | Nisoldipine oral disintegration tablet for treating hypertension and preparing method |
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| CN1562013A true CN1562013A (en) | 2005-01-12 |
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|---|---|---|---|
| CN 200410032067 Pending CN1562013A (en) | 2004-03-31 | 2004-03-31 | Nisoldipine oral disintegration tablet for treating hypertension and preparing method |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100335055C (en) * | 2005-04-29 | 2007-09-05 | 邢为藩 | Pitavastatin soluble tablet composition and preparation method thereof |
| CN107115303A (en) * | 2016-02-25 | 2017-09-01 | 江西天施康中药股份有限公司 | A kind of Nisoldipine oral disintegration tablet and preparation method thereof |
| CN108743553A (en) * | 2018-08-09 | 2018-11-06 | 河北赛克药业有限公司 | A kind of Nitrendipine Tablet and preparation method thereof |
| US20200078295A1 (en) * | 2006-05-19 | 2020-03-12 | Currax Pharmaceuticals Llc | Low Dose Doxepin Formulations, Including Buccal, Sublingual And Fastmelt Formulations, And Uses Of The Same To Treat Insomnia |
| CN117092046A (en) * | 2023-08-03 | 2023-11-21 | 首都医科大学附属北京安定医院 | Method for detecting whether oral cavity of mental patient is hidden with medicine |
-
2004
- 2004-03-31 CN CN 200410032067 patent/CN1562013A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100335055C (en) * | 2005-04-29 | 2007-09-05 | 邢为藩 | Pitavastatin soluble tablet composition and preparation method thereof |
| US20200078295A1 (en) * | 2006-05-19 | 2020-03-12 | Currax Pharmaceuticals Llc | Low Dose Doxepin Formulations, Including Buccal, Sublingual And Fastmelt Formulations, And Uses Of The Same To Treat Insomnia |
| CN107115303A (en) * | 2016-02-25 | 2017-09-01 | 江西天施康中药股份有限公司 | A kind of Nisoldipine oral disintegration tablet and preparation method thereof |
| CN108743553A (en) * | 2018-08-09 | 2018-11-06 | 河北赛克药业有限公司 | A kind of Nitrendipine Tablet and preparation method thereof |
| CN117092046A (en) * | 2023-08-03 | 2023-11-21 | 首都医科大学附属北京安定医院 | Method for detecting whether oral cavity of mental patient is hidden with medicine |
| CN117092046B (en) * | 2023-08-03 | 2024-03-08 | 首都医科大学附属北京安定医院 | Method for detecting whether oral cavity of mental patient is hidden with medicine |
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