CN1864701A - A Chinese medicinal membrane agent capable of being dissolved rapidly in oral cavity and preparation method thereof - Google Patents
A Chinese medicinal membrane agent capable of being dissolved rapidly in oral cavity and preparation method thereof Download PDFInfo
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Abstract
The present invention relates to one kind of Chinese medicine film preparation capable of dissolving in oral cavity fast. The film preparation consists of active Chinese medicine component(s) in 0.1-99 wt%, filming material in 0.1-90 wt% and medicinal supplementary material in 0-30 wt%. The active Chinese medicine components includes red sage extract, total arasaponin, breviscapine, gastrodine, acetyl gastrodine, etc. The Chinese medicine film preparation has convenient taking, fast absorption, high bioavailability, less irritation to digestive tract mucous membrane and other advantages, and is especially suitable for use in treating acute cardiac and cerebral vascular diseases and migraine.
Description
Technical field
The present invention relates to field of traditional Chinese say so more specifically a kind of treatment cardiovascular and cerebrovascular vessel, migrainous Chinese medicine compound or single medicinal material rapidly-soluble membrane agent and preparation method thereof in the oral cavity.
Background technology
According to World Health Organization (WHO) 1996, the number that cardiovascular and cerebrovascular disease is died from the whole world every year reached 1,460 ten thousand people.The sickness rate of China's cardiovascular and cerebrovascular disease is 6%, and there are more than 7,500 ten thousand patients in the whole nation.Because the impact of aged tendency of population, China's annual cardiovascular neopathy number is 1,500,000 people.Cardiovascular and cerebrovascular vessel patient's increase causes the growth to this type of drug demand amount.The sale of China's cardiovascular quasi drugs has been only second to anti-flu and gastrointestinal tract class medicine, occupies the 3rd.
The exploitation that needs new Chinese medicine that improves along with people's living standard should be complied with people, and the new drug of the pursuit performance Chinese medicine advantage of high-quality life style and characteristic is satisfied people's demand personalized and that multiformity is consumed is the direction that the people in the industry lays siege to.At the advantage that Chinese medicine had, it is particularly important that the novel form that lacks in the developing target market---oral thin film just seems.
Chinese medicine plays an important role in above-mentioned prevention and treatment of diseases and confirms through clinical test for many years: effectively Chinese medicine compound or single medicinal material can make things convenient for the patient to use by changing dosage form, have kept original curative effect to make the modern Chinese medicine novel form better be patient's service simultaneously again.Therefore, the inventor releases emergency case medication novel form---and rapidly-soluble membrane agent in the oral cavity is used for the treatment of diseases such as cardiovascular and cerebrovascular vessel, migraine.
At present, the treatment cardiovascular and cerebrovascular vessel, disease conventional Chinese medicine compound recipe such as angina pectoris, migraine or single medicinal material comprise that coronary heart disease, coronary disease Soviet Union close medicines such as Herba Erigerontis, Semen Ginkgo, Radix Notoginseng, gastrodine, acegastrodine.Coronary heart disease prescription for example: Radix Salviae Miltiorrhizae, Radix Notoginseng, Lignum Dalbergiae Odoriferae oil are formed, (function with cure mainly) blood circulation promoting and blood stasis dispelling, regulating QI to relieve pain.Be used for uncomfortable in chest due to the qi stagnation blood stasis, disease is seen thoracic obstruction twinge, shortness of breath and palpitation; Angina pectoris is seen above-mentioned patient.
Breviscapine is, the mixture of the lamp-dish flower acetic that extracts in the distinctive feverfew Herba Erigerontis in Yunnan and a small amount of oil lamp cycle of sixty years element, and the lamp-dish flower acetic chemistry is by name: 4,5,6-trihydroxyflavone-7-glucuronide.Function with cure mainly: blood circulation promoting and blood stasis dispelling, removing obstruction in the collateral to relieve pain.Be used for apoplexy sequela, coronary heart disease, angina pectoris.
Gastrodine is used for that god declines, god declines syndrome and disease such as angioneurotic headache such as migraine, trigeminal neuralgia, occipital bone neuralgia etc.
Acegastrodine, its calm index of the same analog derivative of the calm active ingredient gastrodine in the Chinese medicine Rhizoma Gastrodiae is strong 1.77 times than gastrodine, and chemistry is by name: its benzene-2` of 4-hydroxyl first, 3`, 4`, 6`-four-O acetyl-β-D-pyranglucoside.Effect: calm, sleep peacefully, ease pain.Be applicable to (1) treatment sleep disorder, improve sleep quality; Neurasthenia, neurasthenia syndrome, anxiety neurosis etc. and the sleep disorder that causes thereof; (2) treatment headache, migraine.
Radix Notoginseng total arasaponins is that the extract of panax araliaceae plant mainly contains notoginseng triol and notoginseng diol function and cures mainly: blood circulation promoting and blood stasis dispelling, it is active to promote blood circulation, and the effect with anticoagulant and increase heart and brain blood flow is used for the stasis of blood resistance of brain road, apoplectic hemiplegia, the resistance of the heart arteries and veins stasis of blood stasis of blood, obstruction of qi in the chest and cardialgia; Apoplexy sequela, angina pectoris belong to above-mentioned patient.
Protoparaxotriol saporlirs is that the extract of panax araliaceae plant mainly contains the ginsenoside Rg
1, Re and Panax Notoginseng saponin R
1, function with cure mainly: blood circulation promoting and blood stasis dispelling, it is active to promote blood circulation, and improves cerebral infarction, the cerebral ischemia dysfunction is recovered ischemic brain metabolic abnormality antiplatelet aggregation, prevents the thrombosis microcirculation improvement, reduces whole blood viscosity.Be mainly used in cardiovascular and cerebrovascularinfarction sexually transmitted disease (STD) disease, be used for apoplexy, hemiplegia, crooked mouth and tongue, the treatment of hemianesthesia.
Mainly contain flavonol glycosides, total terpenoid lactone in the Folium Ginkgo extract, function with cure mainly: activating blood circulation to dissipate blood stasis and dredge the collateral is used for obstruction of qi in the chest and cardialgia, apoplexy, hemiplegia that obstruction of collaterals by blood stasis causes, stiff tongue and retardation in speech; Coronary heart disease stable angina pectoris, cerebral infarction are seen above patient.
Above-mentioned these Chinese medicines are dosage forms such as tablet and powder agent, capsule, soft capsule, injection, drop pill having demonstrated better therapeutic effect but treated coronary heart disease, angina pectoris, migrainous Chinese medicine compound or single medicinal material at present aspect treatment angina pectoris, the migraine mostly, the medicine novel form that is used for emergency case fast in the oral cavity dissolved membrane agent do not see bibliographical information still in development.
Summary of the invention
First purpose of the present invention is, a kind of Chinese medicine compound or single medicinal material treatment cardiovascular and cerebrovascular vessel of containing are provided, migrainous in the oral cavity fast quick-dissolving membrane agent.
Purpose of the present invention second is, the preparation method that contains Chinese medicine compound or single medicinal material rapidly-soluble membrane agent in the oral cavity is provided.
Physiology provided by the invention can be accepted thin film, contain one or more active ingredient of Chinese herbs, in the oral cavity, discharge medicine, absorbed by oral mucosa rapidly, thus be particularly suitable for adhering and be dissolved in fast in the oral cavity of user dissolving films onset fast through the oral cavity, through mucous membrane discharges the active substance performance drug effect of medicine.
The invention still further relates to and prepare the softish non-method that is particularly suitable for oral administration from adhering thin film.This method comprises: film former and at least a stabilizing agent are mixed obtaining the film forming mixture and water-soluble component is dissolved in obtains aqueous solution or solvent solution in water or the solvent; Film forming mixture and aqueous solution or solvent solution solvent solution mixed obtain the aqueous polymer gel and mix oils and form oil mixture and oil mixture is added in the hydrated polymer gel and mixes obtain the uniformly emulsify gel; Should spread upon on the substrate by even gel; The gel that drying is smeared obtains thin film.
Concrete technical scheme of the present invention is as follows: treatment cardiovascular and cerebrovascular vessel, migrainous Chinese medicine compound or the quick dissolving films agent of single medicinal material, and film dissolves on tongue in the air less than 1 minute or several seconds at mouth, it is characterized in that this membrane agent is made up of following compositions:
One or more active ingredient of Chinese herbs of 0.1-99%;
The 0.1-90% filmogen;
The 0-30% pharmaceutic adjuvant.
Chinese medicine compound of the present invention or single medicinal material pelliculae pro cavo oris, composed as follows preferably:
One or more active ingredient of Chinese herbs of 10-80%;
The 10-60% filmogen;
The 0.01-30% pharmaceutic adjuvant.
Active ingredient of Chinese herbs of the present invention comprises the coronary heart disease extract; Or
The Radix Notoginseng total arasaponins of the preferred 80-99% of content 5-100%; Or
The protoparaxotriol saporlirs of the preferred 80-99% of content 5-100%; Or
Content 15-100%, the breviscapine of preferred 85-99%; Or
Content is 10-100%, the gastrodine of preferred 85-99%; Or
Content is 25-100%, the acegastrodine of preferred 85-99%; Or
Contain flavonol glycosides 24-50% in the Folium Ginkgo extract, total terpenoid lactone 6-15%.
The preparation of each Chinese medicine effective component extracts of the present invention adopts known conventional method to obtain.(Radix Notoginseng total arasaponins, breviscapine, Semen Ginkgo, gastrodine, acegastrodine.Can water or arbitrary proportion ethanol, methanol, acetone, chloroform, ethyl acetate, petroleum ether, n-butyl alcohol, cyclohexane extraction be solvent, through decoction, precipitate with ethanol, hot reflux, percolation, ultrasonic, silica gel, macroporous adsorptive resins purification, means separation, enrichment, purification such as microwave, the extraction of pH value gradient make, or by the synthetic method preparation).
Filmogen of the present invention comprises: dextran, dextrin, chitin, chitosan, sodium alginate, arabic gum, pectin, collagen; Cellulose is carboxymethyl cellulose sodium, methylcellulose, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyvinylpyrrolidine west ketone, vinylpyrrolidone-vinyl acetate-copolymer; Or amylopectin, amylose, senior amylose, the senior amylose of hydroxypropylation, zein, soy protein isolate, preferably polyethylene ketopyrrolidine, vinylpyrrolidone-vinyl acetate-copolymer, methylcellulose, hydroxypropyl cellulose, sodium alginate, arabic gum, pectin, collagen or the like.
Pharmaceutic adjuvant of the present invention is the 0-30% that plasticizer surfactant, sweeting agent, antiadhesives, correctives, stabilizing agent, thickening agent one or more its weight of mixture wherein accounts for the thin film total amount.Be preferably 0.01-30%, can be according to the physicochemical property of the active component in the different pharmaceutical and biological nature suitable in addition adjusting for example plasticity adds: plasticizer (starch glycerin, propylene glycol, Polyethylene Glycol) in order to make film have preferably.Antiadhesives (magnesium stearate, stearic acid, emulsifying agent).
Correctives comprises natural or artificial correctives.These correctivess can be selected from flavoring oil and flavoring aromatic or their mixture.Representative flavoring oil comprises: the artificial natural or synthetic fruit correctives that also has that Oleum Menthae Rotundifoliae, Oleum Cinnamomi, Oleum menthae, cloves oil, laurel fat, thyme oil are suitable for comprises Fructus Citri Limoniae, Fructus Vitis viniferae, Fructus Mali pumilae, pears, essence, lemon acid, Oleum Eucalypti, peppermint essence wet goods.The consumption of correctives is general relevant with such factor as correctives type, correctives itself with expect that intensity is relevant.Can change this change of this consumption in order to achieve desired results in end product be that one of ordinary skill in the art need not too much to test just can make.Usually, consumption is about 0 to about 30 weight %, and preferred about 0.1 to about 15 weight %.
Sweeting agent comprises natural and artificial sweetening agent, and for example saccharin sodium, A Si BATANG, xylitol, mannitol, neohesperidin, galactose, glycyrrhizin, sucrose, dihydro are looked into bucket ketone etc.Generally be said composition 0% to about 10 weight %.Preferred about 0.1 to about 5 weight %.For obtaining the sugariness of expection, the consumption of use is decided according to different samples.
Surfactant comprises monoglyceride and the Diglyceride compounds and the polyethylene glycol oxide sorbitol ester of fatty acid, as Atmos 300, polysorbate 80, sorbester p38 etc.The addition of surfactant can be this thin film about 0.1 to about 15 weight %, preferred about 0.1 to about 5 weight %.Other suitable surfactant comprises sodium lauryl sulphate etc.
Stabilizing agent comprises xanthan gum, tracasol and carrageenin, consumption be this thin film about 0 to about 10 weight %, preferred about 0.1 to about 2 weight %.Other stabilizing agent that is suitable for comprises Semen Benincasae glue etc.
Emulsifying agent comprises triethanolamine stearate, quaternary ammonium compound; Arabic gum, gelatin, lecithin, colloidal magnesium aluminosilicate etc., consumption is about 0 to about 5 weight % of this thin film, preferred about 0.01 to about 0.8 weight %.
Thickening agent comprises methylcellulose, carboxymethyl cellulose etc., and consumption is about 0 to about 30 weight %, and preferred about 0.01 to about 20 weight %.Binding agent comprises starch, and consumption is about 0 to about 30 weight %, and preferred about 0.1 to about 10 weight %.
The consumption that medicine film of the present invention can also add coloring agent or colorant coloring agent can effectively produce the color and luster of expection.The present invention is used sees and comprises pigment for toner, titanium dioxide for example, and its combined amount is to about 5 weight %, preferably less than about 1 weight %.Colorant also can comprise natural food colors such as Monas cuspurpureus Went, Gardenia Yellow, curcumin and be applicable to food and the dyestuff of medicine
So because effective separately composition of the compound recipe of Chinese medicine or single medicinal material or position are that difference adjuvant and preparation method are to be allowed a choice: the prerequisite that medicine reaches quick fusion is to need polymer to have solubility preferably when medicine dissolves with molecular forms, amorphism, disintegration rate is should have bigger polarity by the quick dissolved substance that the dissolution velocity of carrier and special surface are determined, as dextran, dextrin, sodium alginate, arabic gum, polyvinyl alcohol, polyvinylpyrrolidone and cellulose family have solubility preferably thereby medicine and polar group can produce interaction with polymer.Otherwise the minority polar medicine exists high supersaturation concentration owing to the reason generation recrystallization of temperature makes rate of release decline carrier unformed, that dissolubility is good help the release of dissolving fast and quickening active substance.
The preparation method of treatment cardiovascular and cerebrovascular vessel of the present invention, migrainous Chinese medicine compound or single medicinal material oral thin film specifically comprises the steps:
1) with active component, water-soluble polymer dissolves at water or ethanol methanol, positive alcohol, in acetone, ethyl acetate, the chloroform; Solvent is water or ethanol, acetone, ethyl acetate or the like preferably.
2) dissolve or other the adjuvant of suspending;
3) smear this solution on the silicone rubber paper or on the suitable carriers thing;
4) under 35-65 ℃ of temperature dry 2-120 minute;
5) semi-finished product that drying is good cut or mould is separated the film that obtains the defined size by shearing;
6) packing is separated the film that obtains.
The present invention contains the polymeric film of active substance by smearing organic solvent or the aqueous solution drying that contains active substance, makes.The water-soluble polymer that uses is dextran, dextrin, sodium alginate, arabic gum, polyvinyl alcohol, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate-copolymer, sodium carboxymethyl cellulose, methylcellulose, hydroxyethyl-cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose.In addition, the selection of polyvinyl alcohol, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate-copolymer be according to them in water or the dissolubility in the organic solvent (ethanol).Use steam pressure that the latter is that having of it is higher and rate of drying preferably.
Below by the pharmacological experimental data of active ingredient of Chinese herbs, further set forth good effect of the present invention: coronary heart disease:
(1) coronary heart disease is to the protective effect of rat heart muscle ischemia
Healthy Wistar rat, male, body weight 250 ± 50g.Be divided into 4 groups at random by body weight, 10 every group.4,8 times by human dosage are provided with dosage, administration every day 1 time, continuous 5 days.1h after the last administration, after lumbar injection chloral hydrate (350mg/kg) anesthesia, measure the normal electrocardiogram of II correcting, open the thoracic cavity, with annular hook heart is pulled out thoracic cavity Coronary vein between the mid point of arterial cone and left auricle and sentence silk thread ligation arteria coronaria left anterior descending branch No. 5/0; Heart is put go back to the thoracic cavity, extract air stitching in the thoracic cavity out.After the ligation 30,60min record II leads electrocardiogram, measures the situation of raising of ST section (J point).The result shows that coronary heart disease has significant protective effect (seeing Table 1) to the rat heart muscle ischemia of caused by ligature, suppresses the rising of ST section.
Table 1 coronary heart disease to the influence of rat heart muscle ischemia (x ± s, n=10)
| Group | Value (mV) before the medicine | 30min behind the medicine (mV) | 60min behind the medicine (mV) |
| The high coronary heart disease preparation of blank group model matched group coronary heart disease preparation is low | 0.00±0.00 0.02±0.03 0.03±0.04 0.03±0.04 | 0.00±0.00*** 0.45±0.11 0.22±0.12** 0.25±0.13** | 0.00±0.00*** 0.38±0.17 0.21±0.13* 0.20±0.12* |
Compare with model control group,
*P＜0.05,
*P＜0.01,
* *P＜0.001
(2) coronary heart disease is to the thrombotic influence of rat experiment
Healthy Wistar rat, male and female dual-purpose, body weight 200 ± 20g.Be divided into 3 groups at random by body weight, 10 every group.4,8 times by human dosage are provided with dosage, administration every day 1 time, continuous 5 days.1h after the last administration, after lumbar injection chloral hydrate (350mg/kg) anesthesia, dorsal position is fixed, and separates common carotid artery, the experimental thrombus in vivo of BT87-3 type is formed on the stimulating electrode and temperature probe hook of analyzer, and temperature probe leans on proximal part at the distal end stimulating electrode.Temperature control current intensity 80 μ A, stimulating current 2mA behind the stimulation 5min, takes off stimulating electrode, waits for that again 3min returns to zero temperature control current intensity.Record begins to the required time of tremulous pulse temperature decrease (s), as the artery thrombosis time from stimulation.The result shows that coronary heart disease obviously prolongs the formation time (seeing Table 2) of thrombosis.
Table 2 coronary heart disease to the thrombotic influence of rat experiment (x ± s, n=10)
| Group | Thrombus formation time (s) |
| The high coronary heart disease preparation of blank group coronary heart disease preparation is low | 650±104 1000±120* 855±107* |
Compare with model control group:
*P＜0.05.
Radix Notoginseng total arasaponins:
(1) Radix Notoginseng total arasaponins is to the influence of platelet aggregation reaction
Choose healthy rabbits, male, body weight 2.5-3kg, experiment is divided into 3 groups, random packet, 6 every group, 4,8 times by clinical dosage are provided with dosage respectively, and successive administration 5 days after the last administration 1 hour, is got blood and is experimentized.Get blood (with 3.8% sodium citrate anticoagulant, whole blood and anticoagulant are 9: 1) from the rabbit common carotid artery, the centrifugal 10min of 800rpm, preparation platelet rich plasma (PRP), centrifugal 10 minutes again, preparation platelet poor plasma (PPP) through 3500rpm.Behind the pre-temperature of blood plasma (37 ℃) 30min, transfer 100% with PPP, with the PRP zeroing, add respectively ADP, AA, collagen-induced dose, measure platelet aggregation percent by turbidimetry with platelet aggregation instrument, calculate the aggreation suppression ratio.The result shows that Radix Notoginseng total arasaponins obviously suppresses the inductive platelet aggregation reaction of derivant (seeing Table 3).
The inhibitory action that table 3 Radix Notoginseng total arasaponins reacts the rabbit platelet aggregation (X ± SD, n=6)
| Group | ADP suppression ratio (%) | AA suppression ratio (%) | Collagen suppression ratio (%) |
| The high Radix Notoginseng total arasaponins of blank group Radix Notoginseng total arasaponins is low | - 78.6 59.7 | - 87.2 78.9 | - 78.4 60.8 |
(2) Radix Notoginseng total arasaponins is to the thrombotic influence of rat experiment
Healthy Wistar rat, male and female dual-purpose, body weight 200 ± 20g.Be divided into 3 groups at random by body weight, 10 every group.4,8 times by human dosage are provided with dosage, administration every day 1 time, continuous 5 days.1h after the last administration, after lumbar injection chloral hydrate (350mg/kg) anesthesia, dorsal position is fixed, and separates common carotid artery, the experimental thrombus in vivo of BT87-3 type is formed on the stimulating electrode and temperature probe hook of analyzer, and temperature probe leans on proximal part at the distal end stimulating electrode.Temperature control current intensity 80 μ A, stimulating current 2mA behind the stimulation 5min, takes off stimulating electrode, waits for that again 3min returns to zero temperature control current intensity.Record begins to the required time of tremulous pulse temperature decrease (s), as the artery thrombosis time from stimulation.The result shows that Radix Notoginseng total arasaponins obviously prolongs the formation time (seeing Table 4) of thrombosis.
Table 4 Radix Notoginseng total arasaponins to the thrombotic influence of rat experiment (x ± s, n=10)
| Group | Thrombus formation time (s) |
| The high Radix Notoginseng total arasaponins preparation of blank group Radix Notoginseng total arasaponins preparation is low | 650±104 1000±120* 855±107* |
Compare with model control group:
*P＜0.05.
Protoparaxotriol saporlirs:
Protoparaxotriol saporlirs is to the thrombotic influence of rat experiment
Healthy Wistar rat, male and female dual-purpose, body weight 200 ± 20g.Be divided into 3 groups at random by body weight, 10 every group.4,8 times by human dosage are provided with dosage, administration every day 1 time, continuous 5 days.1h after the last administration, after lumbar injection chloral hydrate (350mg/kg) anesthesia, dorsal position is fixed, and separates common carotid artery, the experimental thrombus in vivo of BT87-3 type is formed on the stimulating electrode and temperature probe hook of analyzer, and temperature probe leans on proximal part at the distal end stimulating electrode.Temperature control current intensity 80 μ A, stimulating current 2mA behind the stimulation 5min, takes off stimulating electrode, waits for that again 3min returns to zero temperature control current intensity.Record begins to the required time of tremulous pulse temperature decrease (s), as the artery thrombosis time from stimulation.The result shows that protoparaxotriol saporlirs obviously prolongs the formation time (seeing Table 5) of thrombosis.
Table 5 protoparaxotriol saporlirs to the thrombotic influence of rat experiment (x ± s, n=10)
| Group | Thrombus formation time (s) |
| The high protoparaxotriol saporlirs preparation of blank group protoparaxotriol saporlirs preparation is low | 655±114 996±112* 833±109* |
Compare with model control group:
*P＜0.05.
Breviscapine:
(1) breviscapine is to the influence of platelet aggregation reaction
Choose healthy rabbits, male, body weight 2.5-3kg, experiment is divided into 3 groups, random packet, 6 every group, 4,8 times by clinical dosage are provided with dosage respectively, and successive administration 5 days after the last administration 1 hour, is got blood and is experimentized.Get blood (with 3.8% sodium citrate anticoagulant, whole blood and anticoagulant are 9: 1) from the rabbit common carotid artery, the centrifugal 10min of 800rpm, preparation platelet rich plasma (PRP), centrifugal 10 minutes again, preparation platelet poor plasma (PPP) through 3500rpm.Behind the pre-temperature of blood plasma (37 ℃) 30min, transfer 100% with PPP, with the PRP zeroing, add respectively ADP, AA, collagen-induced dose, measure platelet aggregation percent by turbidimetry with platelet aggregation instrument, calculate the aggreation suppression ratio.The result shows that breviscapine obviously suppresses the inductive platelet aggregation reaction of derivant (seeing Table 6).
The inhibitory action that table 6 breviscapine reacts the rabbit platelet aggregation (X ± SD, n=6)
| Group | ADP suppression ratio (%) | AA suppression ratio (%) | Collagen suppression ratio (%) |
| The high breviscapine of blank group breviscapine is low | - 75.4 55.6 | - 86.1 73.2 | - 74.3 62.1 |
Gastrodine:
The inhibitory action that table 7 gastrodine reacts the rabbit platelet aggregation (X ± SD, n=6)
| Group | ADP suppression ratio (%) | AA suppression ratio (%) | Collagen suppression ratio (%) |
| The high gastrodine of blank group gastrodine is low | - 78.6 59.7 | - 87.2 78.9 | - 78.4 60.8 |
The result shows that gastrodine obviously suppresses the inductive platelet aggregation reaction of derivant (seeing Table 7).
Table 8 gastrodine to the influence of mice pain threshold values (X ± SD, n=6)
| Group | Before the administration | After the administration | |
| 0.5h | 1h | ||
| The high gastrodine of blank group gastrodine is low | 20.2±4.5 25.9±9.2 20.3±8.6 | 26.1±±13.3 34.1±12.3 30.2±15.1 | 25.7±12.3 43.6±16.7 * 42.2±17.0 * |
Compare with model control group:
*P＜0.05.
The result shows, the obvious analgesic activity of gastrodine (seeing Table 8).
Acegastrodine:
The inhibitory action that table 9 acegastrodine reacts the rabbit platelet aggregation (X ± SD, n=6)
| Group | ADP suppression ratio (%) | AA suppression ratio (%) | Collagen suppression ratio (%) |
| The high acegastrodine of blank group acegastrodine is low | - 73.6 58.97 | - 82.4 76.3 | - 73.5 66.2 |
The result shows that acegastrodine obviously suppresses the inductive platelet aggregation reaction of derivant (seeing Table 9).
Table 10 acegastrodine to the influence of mice pain threshold values (X ± SD, n=6)
| Group | Before the administration | After the administration | |
| 0.5h | 1h | ||
| Blank group acegastrodine hangs down the acegastrodine height | 20.2±4.5 20.9±8.8 20.4±6.6 | 26.1±13.3 33.1±11.2 36.2±11.4 | 25.7±12.3 39.4±13.7 * 45.2±13.9 * |
Compare with model control group:
*P＜0.05.
The result shows, the obvious analgesic activity of acegastrodine (seeing Table 10).
The stability experiment of medicine film
According to the pertinent regulations of " specification requirement of study of tcm new drug ", carried out the room temperature natural reserved and investigated.At room temperature placed 12 months in aeration-drying place, by character, discriminating, melting, assay, microbial limit and six aspects of moisture stability being investigated the result shows, the coronary heart disease extract, Radix Notoginseng total arasaponins, the medicine film that breviscapine, gastrodine, the acegastrodine of sleeping peacefully are made is placed and was stablized in 12 months.
Pelliculae pro cavo oris of the present invention is compared with conventional dosage forms such as tablet, capsules, and it has taking convenience, absorbs fast, bioavailability advantages of higher; Compare with injection, patient is acceptant, reduces the side effect that directly enters blood and cause, and time is life concerning first-aid patients, is significant so develop this quick dissolving films agent, also is the characteristics that embody this dosage form.The good effect of thin film of the present invention is:
(1) film that contains active substance can be taken lacking under the situation of water.Polymeric film dissolves on tongue in less than 1 minute or several seconds, and buccal is in the oral cavity or the Sublingual, swallows that can to dissolve the drug metabolism processes that absorbs them rapidly when taking in gastrointestinal be similar, to the emergency case patient be a kind of rapid-action administration the best by way of.
(2) advantage of comparing with lyophilized powder is the simple of preparation method, and cost is low, and this product has a spot of hygroscopicity but needn't use packaging material expensive, waterproof steam in addition.
(3) this dosage form and solid preparation (tablet, capsule, drop pill etc.) are relatively, it is fast, rapid-action to have dissolving, improve bioavailability, be specially adapted to the emergency case medicine, as cardiovascular and cerebrovascular vessel, ease pain, sleep peacefully etc., its advantage is that medicine dissolves immediately, and is also unquestionable to the patient of dysphagia, is fit to uncooperative patient's use (child and old man) equally; When travelling or water inconvenience, can take equally, very thin a slice film is swallowed conveniently, enters the interior back of body active treatment composition and is easy to discharge from carrier, makes things convenient for the patient to use, and patient is easy to accept.
(4) membrane technology of the present invention is simple, economy, and practicality is suitable for large-scale industrial production.
The specific embodiment
The present invention is described further below in conjunction with embodiment, and the embodiment instrument is indicatively to mean that never it limits the scope of the invention by any way.
Embodiment 1
Coronary heart disease extract 3.0g, 2.0gHPC, 5.0g polyvinylpyrrolidone, 0.02g stevioside, 0.3g glycerol, be dissolved in the ethanol of 12ml95%, form solution, this solution spreads upon on the silicone rubber paper with squeegee, 350 microns the film of forming 35 ℃ of dryings 30 minutes, continuation is 80g/m 60 ℃ of dryings 30 minutes in plane weight
2Down, formation thickness is 90 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 2
Coronary heart disease extract 4g, 1.7g methylcellulose, 4.5g vinylpyrrolidone-vinyl acetate-copolymer, 0.03g A Si BATANG, 0.1g xanthan gum, 0.4g propylene glycol is dissolved in the ethanol of 12ml50%, forms solution, this solution spreads upon on the silicone rubber paper with squeegee, 300 microns the film of forming 30 ℃ of dryings 30 minutes, continue 60 ℃ of dryings 60 minutes, be 1000g/m in plane weight
2Down, formation thickness is 80 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 3
Coronary heart disease extract 3.2g, 6.5g vinylpyrrolidone-vinyl acetate-copolymer, 0.02g saccharin sodium, 0.3gPEG400, be dissolved in the ethanol of 12ml75%, form solution, this solution spreads upon on the silicone rubber paper with squeegee, the film that institute's shape is 250 microns is 30 ℃ of dryings 30 minutes, continues 60 ℃ of dryings 60 minutes, and be 100g/m in plane weight
2Down, formation thickness is 75 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 4
Breviscapine 2g, 1.7g methylcellulose, 6.5g vinylpyrrolidone-vinyl acetate-copolymer, 0.3g xylitol, 0.3g propylene glycol, 0.1g Herba Menthae quintessence oil, be dissolved in the ethanol of 14ml95%, this solution spreads upon on the silicone rubber paper with squeegee, form 300 microns film 30 ℃ of dryings 30 minutes, continuation is 100g/m 65 ℃ of dryings 30 minutes in plane weight
2Down, formation thickness is 80 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 5
Breviscapine 4g, 3.0gHPC, 4.5g polyvinylpyrrolidone, 0.02g stevioside, 0.2g glycerol, 0.1g polysorbate 80, be dissolved in the ethanol of 12ml90%, this solution spreads upon on the silicone rubber paper with squeegee, form 300 microns film 30 ℃ of dryings 30 minutes, continuation is 100g/m 65 ℃ of dryings 30 minutes in plane weight
2Down, formation thickness is 80 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 6
Radix Notoginseng total arasaponins 2.5g, 1.0g xanthan gum, 4.5g tracasol, 1.5g starch, 0.02g A Si BATANG, 0.2g propylene glycol, the magnesium stearate of 0.05g is dissolved in the ethanol of 14ml95%, this solution spreads upon on the silicone rubber paper with squeegee, 350 microns the film of forming 30 ℃ of dryings 30 minutes, continue 60 ℃ of dryings 60 minutes, be 80g/m in plane weight
2Down, formation thickness is 50 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 7
Radix Notoginseng total arasaponins 2.5g, 2.0gHPC, 3.5g polyvinylpyrrolidone, 0.02g neohesperidin, 0.2g glycerol, be dissolved in the 14ml water, form coagulant liquid, this solution spreads upon on the silicone rubber paper with squeegee, 300 microns the film of forming 30 ℃ of dryings 30 minutes, continuation is 80g/m 60 ℃ of dryings 60 minutes in plane weight
2Down, formation thickness is 80 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 8
Semen Ginkgo extrac 2g, 1.0g xanthan gum, 2.5g tracasol, 1.5g starch, 0.02g A Si BATANG, 0.2g propylene glycol is dissolved in the 14ml water, forms coagulant liquid, this solution spreads upon on the silicone rubber paper with squeegee, 350 microns the film of forming 30 ℃ of dryings 30 minutes, continue 60 ℃ of dryings 60 minutes, be 80g/m in plane weight
2Down, formation thickness is 70 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 9
Semen Ginkgo extrac 2g, 2.0g methylcellulose, 4.0g vinylpyrrolidone-vinyl acetate-copolymer, 0.5g xylitol, 0.3g propylene glycol, 0.1g the Herba Menthae quintessence oil is dissolved in the ethanol of 12ml50%, forms coagulant liquid, this solution spreads upon on the silicone rubber paper with squeegee, 300 microns the film of forming 30 ℃ of dryings 30 minutes, continue 65 ℃ of dryings 30 minutes, be 100g/m in plane weight
2Down, formation thickness is 100 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 10
Gastrodine 2.5g, 1.5g xanthan gum, 3.5g carrageenin, 1.5g starch, 0.01g the A Si BATANG, 0.1g polysorbate 80,0.2g glycerol, be dissolved in the ethanol of 14ml50%, form coagulant liquid, this solution spreads upon on the silicone rubber paper with squeegee, 250 microns the film of forming 35 ℃ of dryings 30 minutes, continuation is 80g/m 65 ℃ of dryings 30 minutes in plane weight
2Down, formation thickness is 60 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 11
Gastrodine 2.5g, 2.0g methylcellulose, 3.0g vinylpyrrolidone-vinyl acetate-copolymer, 0.5g xylitol, 0.3g propylene glycol, be dissolved in the ethanol of 14ml50%, form coagulant liquid, this solution spreads upon on the silicone rubber paper with squeegee, 250 microns the film of forming 35 ℃ of dryings 30 minutes, continuation is 80g/m 65 ℃ of dryings 30 minutes in plane weight
2Down, formation thickness is 60 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 12
Acegastrodine 3.3g, 2.0gHPC, 4.0g polyvinylpyrrolidone, 0.5g xylitol, 0.3g propylene glycol, be dissolved in the ethanol of 14ml50%, form coagulant liquid, this solution spreads upon on the silicone rubber paper with squeegee, 250 microns the film of forming 35 ℃ of dryings 30 minutes, continuation is 80g/m 65 ℃ of dryings 30 minutes in plane weight
2Down, formation thickness is 60 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 13
Acegastrodine 3.3g, 3.0g sodium alginate, 2.5g polyvinylpyrrolidone, 0.02g neohesperidin, 0.2g glycerol, be dissolved in the ethanol of 14ml50%, form coagulant liquid, this solution spreads upon on the silicone rubber paper with squeegee, 300 microns the film of forming 30 ℃ of dryings 30 minutes, continuation is 80g/m 60 ℃ of dryings 60 minutes in plane weight
2Down, formation thickness is 80 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 14
Protoparaxotriol saporlirs 2.5g, 2.5gHPC, 3.0g polyvinylpyrrolidine enzyme 0.5g xylitol, 0.2g glycerol is dissolved in the 14ml water, forms solution, this solution spreads upon on the silicone rubber paper with squeegee, 300 microns the film of forming 30 ℃ of dryings 30 minutes, continue 60 ℃ of dryings 60 minutes, be 80g/m in plane weight
2Down, formation thickness is 80 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Embodiment 15
Protoparaxotriol saporlirs 2.5g, 2.0g methylcellulose, 3.0g vinylpyrrolidone-vinyl acetate-copolymer, 0.02g stevioside, 0.3g propylene glycol, be dissolved in the ethanol of 14ml50%, form coagulant liquid, this solution spreads upon on the silicone rubber paper with squeegee, 250 microns the film of forming 35 ℃ of dryings 30 minutes, continuation is 80g/m 65 ℃ of dryings 30 minutes in plane weight
2Down, formation thickness is 60 microns film, carefully takes off from silicone rubber paper, cuts into the sheet of 2 * 3cm, promptly gets the medicine film.
Claims (6)
1, a kind of in the oral cavity rapidly-soluble Chinese medicine membrane agent it is characterized in that this membrane agent is made up of following compositions:
One or more active ingredient of Chinese herbs of 0.1-99%;
The 0.1-90% filmogen;
The 0-30% pharmaceutic adjuvant.
2, membrane agent as claimed in claim 1 is characterized in that this membrane is made up of following compositions:
One or more active ingredient of Chinese herbs of 10-80%;
The 10-60% filmogen;
The 0.01-30% pharmaceutic adjuvant.
3, membrane agent as claimed in claim 1 or 2, wherein said active ingredient of Chinese herbs comprises the coronary heart disease extract, Radix Notoginseng total arasaponins, breviscapine, Semen Ginkgo, gastrodine or acegastrodine.
4, membrane agent as claimed in claim 1 or 2, wherein said filmogen comprises: dextran, dextrin, chitin, chitosan, sodium alginate, arabic gum, pectin, collagen; Carboxymethyl cellulose sodium, methylcellulose, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate-copolymer; Or amylopectin, amylose, senior amylose, the senior amylose of hydroxypropylation, zein, soy protein isolate.
5, membrane agent as claimed in claim 1 or 2, wherein said pharmaceutic adjuvant comprise plasticizer, surfactant, sweeting agent, antiadhesives, correctives, stabilizing agent, thickening agent one or more mixture wherein.
6, a kind of in the oral cavity preparation method of rapidly-soluble Chinese medicine membrane agent, comprise the steps:
1) with active component, polymer dissolution at water or ethanol, methanol, n-butyl alcohol, in acetone, ethyl acetate, the chloroform;
2) dissolve or other the adjuvant of suspending;
3) smear this solution on the silicone rubber paper or on the suitable carriers thing;
4) under 35-65 ℃ of temperature dry 2-120 minute;
5) semi-finished product that drying is good cut or mould is separated the film that obtains the defined size by shearing;
6) packing is separated the film that obtains.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200510013538 CN1864701A (en) | 2005-05-20 | 2005-05-20 | A Chinese medicinal membrane agent capable of being dissolved rapidly in oral cavity and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200510013538 CN1864701A (en) | 2005-05-20 | 2005-05-20 | A Chinese medicinal membrane agent capable of being dissolved rapidly in oral cavity and preparation method thereof |
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|---|---|---|---|
| CN 200510013538 Pending CN1864701A (en) | 2005-05-20 | 2005-05-20 | A Chinese medicinal membrane agent capable of being dissolved rapidly in oral cavity and preparation method thereof |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010510269A (en) * | 2006-11-24 | 2010-04-02 | ディーエスエム アイピー アセッツ ビー．ブイ． | Food and pharmaceutical compositions containing carnosol and / or rosmanol and uses thereof |
| CN101897990A (en) * | 2010-07-06 | 2010-12-01 | 大连理工大学 | Dressing composition used for inhibiting scars and accelerating wound healing and application thereof |
| CN103263402A (en) * | 2013-05-31 | 2013-08-28 | 天津市聚星康华医药科技有限公司 | Water-drinking-free oral drug composition and preparation method thereof |
| CN103340841A (en) * | 2013-07-02 | 2013-10-09 | 康美药业股份有限公司 | Chinese medicine film as well as preparation method and application thereof |
| CN104223078A (en) * | 2014-09-26 | 2014-12-24 | 天津市聚星康华医药科技有限公司 | Tea polyphenol oral cavity instant film and preparation method thereof |
| CN104224757A (en) * | 2014-09-26 | 2014-12-24 | 天津市聚星康华医药科技有限公司 | Instant gastrodin oral membrane and preparation method thereof |
| CN104983700A (en) * | 2015-07-17 | 2015-10-21 | 南昌大学 | Chinese yam polysaccharide instant slice and production method thereof |
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| CN106913617A (en) * | 2017-02-21 | 2017-07-04 | 安徽安龙基因医学检验所有限公司 | A kind of components in danshen oral quick-dissolving film preparation and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2010510269A (en) * | 2006-11-24 | 2010-04-02 | ディーエスエム アイピー アセッツ ビー．ブイ． | Food and pharmaceutical compositions containing carnosol and / or rosmanol and uses thereof |
| CN101897990A (en) * | 2010-07-06 | 2010-12-01 | 大连理工大学 | Dressing composition used for inhibiting scars and accelerating wound healing and application thereof |
| CN101897990B (en) * | 2010-07-06 | 2013-01-02 | 大连理工大学 | Dressing composition used for inhibiting scars and accelerating wound healing and application thereof |
| CN103263402A (en) * | 2013-05-31 | 2013-08-28 | 天津市聚星康华医药科技有限公司 | Water-drinking-free oral drug composition and preparation method thereof |
| CN103340841A (en) * | 2013-07-02 | 2013-10-09 | 康美药业股份有限公司 | Chinese medicine film as well as preparation method and application thereof |
| CN103340841B (en) * | 2013-07-02 | 2016-04-20 | 康美药业股份有限公司 | A kind of Chinese medicine membrane, Preparation Method And The Use |
| CN104223078A (en) * | 2014-09-26 | 2014-12-24 | 天津市聚星康华医药科技有限公司 | Tea polyphenol oral cavity instant film and preparation method thereof |
| CN104224757A (en) * | 2014-09-26 | 2014-12-24 | 天津市聚星康华医药科技有限公司 | Instant gastrodin oral membrane and preparation method thereof |
| CN104983700A (en) * | 2015-07-17 | 2015-10-21 | 南昌大学 | Chinese yam polysaccharide instant slice and production method thereof |
| CN105053900A (en) * | 2015-07-17 | 2015-11-18 | 瑞昌市渝瑞实业有限公司 | Instant Chinese yam chips and preparation method thereof |
| CN106913617A (en) * | 2017-02-21 | 2017-07-04 | 安徽安龙基因医学检验所有限公司 | A kind of components in danshen oral quick-dissolving film preparation and preparation method thereof |
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