CN1562052A - Acetyl-gastrodine oral disintigration tablet for sedation, soporific and nervous headache - Google Patents
Acetyl-gastrodine oral disintigration tablet for sedation, soporific and nervous headache Download PDFInfo
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- CN1562052A CN1562052A CN 200410039846 CN200410039846A CN1562052A CN 1562052 A CN1562052 A CN 1562052A CN 200410039846 CN200410039846 CN 200410039846 CN 200410039846 A CN200410039846 A CN 200410039846A CN 1562052 A CN1562052 A CN 1562052A
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- oral cavity
- agent
- adjuvant
- tablet
- cavity disintegration
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- 231100000869 headache Toxicity 0.000 title claims abstract description 10
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- 206010039897 Sedation Diseases 0.000 title 1
- 230000036280 sedation Effects 0.000 title 1
- HGUDVDQXCUHOED-YMQHIKHWSA-N [(2r,3r,4s,5r,6s)-3,4,5-triacetyloxy-6-[4-(hydroxymethyl)phenoxy]oxan-2-yl]methyl acetate Chemical compound CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1OC1=CC=C(CO)C=C1 HGUDVDQXCUHOED-YMQHIKHWSA-N 0.000 claims abstract description 30
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 5
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- 238000000034 method Methods 0.000 claims description 19
- 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
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Landscapes
- Medicinal Preparation (AREA)
Abstract
An oral disintegrating tablet of acegastrodine for treating insomnia and nervous headache is prepared from acegastrodine, souring agent, excipient, and disintegrant.
Description
Technical field
What the present invention relates to is pharmaceutical preparation in the field of medicaments, specifically a kind ofly is used for calmness, sleeps peacefully and the acegastrodine oral cavity disintegration tablet of nervous headache and preparation method thereof.
Technical background
The pharmacological action of acegastrodine shows the corticocerebral process of inhibition of enhancing, presents the brain wave type that maincenter suppresses, and has maincenter tranquilizing soporific effect, and calm index is strong 1.77 times than gastrodine, is the secondary product of gastrodine.And have analgesic activity, but cerebral blood flow increasing amount and alleviate cerebral vasospasm; And electrocardiogram, blood pressure there is not obvious influence.This product at clinical indication is: calm sleeping.Be used for insomnia and headache that anxiety, anxiety, excitement and confirmed fatigue etc. cause.This product drug safety, untoward reaction is low, is difficult in vivo accumulating, and can not influence after taking through two days work and the life active drug for sleep disorder such as a kind of Cure for insomnias.
Medical research is found: along with society and development of science and technology, people's work, rhythm of life are also in continuous quickening, owing to be in a kind of work and living environment of anxiety for a long time, people's sleep quality is also progressively descending, the insomnia rate is high, its reason may be neural and nervous, impels brain blood circulation to accelerate.The operate as normal and the life of not having enough sleep and will have a strong impact on them have become the focus that the whole society pays close attention to.
The acegastrodine preparation only has oral conventional tablet at present, when the patient takes before sleeping night, need with water delivery service acegastrodine tablet, this has brought many inconvenience to the patient, particularly old age and child increase the discharge capacity of urine and feasible the having difficulty in going to sleep of blood circulation of quickening stomach night, and conventional tablet medicine stripping after the gastric disintegrate needs certain hour in addition, so it is slower that the conventional tablet of acegastrodine is taken the back onset, bioavailability is low.
Acegastrodine 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 age and child, 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 and a kind ofly be used for calmness, sleep peacefully and the acegastrodine oral cavity disintegration tablet and the preparation method of nervous headache, the patient only needs oral cavity disintegration tablet of the present invention is put into the oral cavity, need not to drink water, because the salivation amount increases, make that tablet was disintegratable or dissolving in 30 seconds, along with swallowing act is sent medicine into gastric, bring into play drug effect rapidly.
The object of the present invention is achieved like this: be used for calmness, sleep peacefully and the acegastrodine oral cavity disintegration tablet of nervous headache, form by principal agent and adjuvant, wherein:
(1) principal agent: acegastrodine
A. English name: Acetagastrodin
B. chemical name: 4-methylol benzene-2 ', 3 ', 4 ', 6 '-four-o-acetyl-β-D-pyranglucoside.
C. molecular formula: C
21H
26O
11Molecular weight: 454.42
D. structural formula:
Contain principal agent 5-200mg 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 acegastrodine 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 does not clinically need drug administration by injection for treatment neurasthenia, neurasthenic syndrome, angioneurotic headache or high blood pressure disease, and oral administration and need not to drink water can reach clinical therapeutic efficacy.
The patient group that oral cavity disintegration tablet of the present invention mainly is suitable for clinically has: administration patient under patient, the psychosis of not being obedient to oral administration or the child of water restriction, the operate outside anhydrous condition in the patient of gerontal 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: acegastrodine oral cavity disintegration tablet
Specification: 25mg/ sheet
Prescription 1: acegastrodine 25g
Lactose 65g
Crospolyvinylpyrrolidone (CPVP) 4g
Citric acid 0.5g
Aspartame 1g
Flavor powder 0.5g
Magnesium stearate 0.5g
Preparation method: with acegastrodine, 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, principal agent and adjuvant gross weight are about 96.5g, contain principal agent 25mg in every, the about 71.5mg of adjuvant, theoretical sheet heavily is about: the 96.5mg/ sheet.Compacting is 1000 on tablet machine.Adopt the disintegration time mensuration method that designs voluntarily to detect the disintegration time of embodiment 1 made tablet.Method is as follows:
Get a flask that fills normal-temperature water, end with a latex tubing inserts in the water, glass dropper of another termination, the knob of a controllable flow rate is installed in the middle of latex tubing, slowly flow out by water in the flask according to siphon principle, and the control flow velocity, allow the effusive water of glass drop pipe become non-linear shape (being interrupted drip, the drop of similar hospital transfusion).Get the made tablet of a slice and be placed on No. 2 (steel) screen clothes (24 order), move under the glass dropper (tablet is apart from dropper 3-5cm height), observe tablet disintegrate situation, and whole time by sieving for No. 2 after the disintegrate of record tablet.After testing, the disintegration of tablet time of embodiment 1 is 14 seconds.
Embodiment 2
The name of an article: acegastrodine oral cavity disintegration tablet
Specification: 50mg/ sheet
Prescription 2: acegastrodine 50g
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 acegastrodine, stirring all is dissolved in the polyvinylpyrrolidone alcoholic solution medicine, adds tartaric acid, stevioside again, stirs to make it be dissolved into settled solution.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, make 20 order granules by wet method, put 60 ℃ of dry 4h, sneak into magnesium stearate, cross 18 mesh sieve granulate, principal agent and adjuvant gross weight are about 164g, contain principal agent 50mg, adjuvant 114mg in every, theoretical sheet heavily is about the 164mg/ sheet, 1000 of tablet machine compactings.
Adopt the disintegration time mensuration method of formulating voluntarily (seeing embodiment 1) to detect the disintegration time of made tablet.After testing, the disintegration of tablet time of embodiment 2 is 15 seconds.
Embodiment 3
The name of an article: acegastrodine oral cavity disintegration tablet
Specification: 100mg/ sheet
Prescription 3: acegastrodine 100g
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.
The disintegration of tablet time of the embodiment 3 that detects by the disintegration time mensuration method of embodiment 1 is 10 seconds.
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 and contain principal agent acegastrodine 25mg, 50mg, three specifications of 100mg, when this product of preparation, every sheet is heavy variable, and only adjuvant increases or reduces.Other every embodiment method that contains principal agent 5-200mg is the same.
Product clinical indication of the present invention is: calm sleeping.Be used for insomnia that anxiety, anxiety, excitement and confirmed fatigue etc. cause and headache, migraine disease.
This product has to absorb in fast, the body and is difficult for accumulating, and can not influence second day work and life after taking, and drug effect is remarkable.
Claims (8)
1. one kind is used for calmness, sleeps peacefully and the acegastrodine oral cavity disintegration tablet of nervous headache, it is characterized in that prescription is made up of principal agent and adjuvant, wherein:
(1) principal agent: acegastrodine
A. English name: Acetagastrodin
B. chemical name: 4-methylol benzene-2 ', 3 ', 4 ', 6 '-four-o-acetyl-β-D-pyranglucoside.
C. molecular formula: C
21H
26O
11Molecular weight: 454.42
D. structural formula:
Contain principal agent 5-200mg 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 acegastrodine, 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 acegastrodine, 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 acegastrodine, 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 acegastrodine, 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 200410039846 CN1562052A (en) | 2004-03-23 | 2004-03-23 | Acetyl-gastrodine oral disintigration tablet for sedation, soporific and nervous headache |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410039846 CN1562052A (en) | 2004-03-23 | 2004-03-23 | Acetyl-gastrodine oral disintigration tablet for sedation, soporific and nervous headache |
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|---|---|
| CN1562052A true CN1562052A (en) | 2005-01-12 |
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|---|---|---|---|
| CN 200410039846 Pending CN1562052A (en) | 2004-03-23 | 2004-03-23 | Acetyl-gastrodine oral disintigration tablet for sedation, soporific and nervous headache |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104231013A (en) * | 2014-08-26 | 2014-12-24 | 上海现代哈森（商丘）药业有限公司 | Gastrodin ferulate compound and preparation method and application of gastrodin ferulate compound |
| CN106176792A (en) * | 2016-07-12 | 2016-12-07 | 昆明学院 | 7 O β D glycosyl coumarins purposes in the medicine of preparation treatment anxiety neurosis |
-
2004
- 2004-03-23 CN CN 200410039846 patent/CN1562052A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104231013A (en) * | 2014-08-26 | 2014-12-24 | 上海现代哈森（商丘）药业有限公司 | Gastrodin ferulate compound and preparation method and application of gastrodin ferulate compound |
| CN106176792A (en) * | 2016-07-12 | 2016-12-07 | 昆明学院 | 7 O β D glycosyl coumarins purposes in the medicine of preparation treatment anxiety neurosis |
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