CN102961365B - Terbutaline sulphate oral instant membrane and preparation method thereof - Google Patents
Terbutaline sulphate oral instant membrane and preparation method thereof Download PDFInfo
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- CN102961365B CN102961365B CN201210548234.0A CN201210548234A CN102961365B CN 102961365 B CN102961365 B CN 102961365B CN 201210548234 A CN201210548234 A CN 201210548234A CN 102961365 B CN102961365 B CN 102961365B
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- Prior art keywords
- terbutaline sulphate
- terbutaline
- membrane
- oral instant
- instant membrane
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- KFVSLSTULZVNPG-UHFFFAOYSA-N terbutaline sulfate Chemical compound [O-]S([O-])(=O)=O.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1 KFVSLSTULZVNPG-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 239000012528 membrane Substances 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title abstract description 14
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 24
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 14
- 239000004408 titanium dioxide Substances 0.000 claims description 12
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 11
- 229960000195 terbutaline Drugs 0.000 claims description 11
- 239000000049 pigment Substances 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
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- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 5
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention belongs to medical art, disclose oral instant membrane of a kind of terbutaline sulphate and preparation method thereof.Terbutaline sulphate oral instant membrane of the present invention, active component terbutaline sulphate, filmogen, disintegrating agent and opacifier containing effective dose; And the acceptable filler of the pharmacy of necessity, sweeting agent, wetting agent; Also can add coloring agent as required.The agreeable to the taste degree of the present invention is good, it is molten, rapid-action to collapse rapidly in oral cavity, and volume is little, do not need, with water delivery service, to be applicable to child, old age, to be unable to leave the bed and severe disability patient, and people's medication at any time when inconvenience is drunk water.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of oral instant membrane containing terbutaline sulphate and preparation method thereof.It is once contact with saliva of buccal cavity, very soon dissolve or disintegrate, rapid-action and have take, easy to carry, do not need by features such as water delivery services.Can be relaxed bronchial smooth muscle, the edema suppressing endogenous to cause the release of spasm material and endogenous mediator to cause; Strengthen bronchial mucosa epithelial cell fiber movement, accelerate mucus and eliminate, have bronchorelaxing activity; Be effective to bronchial asthma, chronic asthma bronchitis, obstructive emphysema and other treatments with bronchospasm pulmonary disease.
Background technology
Along with improving constantly of people's living standard, the health care consciousness of people also strengthens gradually, starts the generation more paying close attention to some diseases; But, along with the improvement of people's living standard, under the impact of air pollution and ecological deterioration in the world, make a lot of people still keep away the invasion and attack of unavoidable asthma.In recent years, the M & M of asthma presents ever-increasing trend, has become a kind of major chronic illnesses threatening public health.Asthma not only serious harm people physically and mentally healthy, weaken work capacity, reduce quality of life, and be difficult to radical cure.Its easy recurrent exerbation, can threat to life time serious.Because asthma is a kind of anaphylactic disease, unlike infectious disease, have infector, can prevent with vaccine, ensure patient for a long time, correctly medication, can effectively prevention of asthma show effect.
Terbutaline sulphate (terbutalinesulphate, 1) also known as terbutaline, it is first generation beta 2 receptor agonist, there is stronger mastocyte membrane stabilizing action, alternative excited beta 2-adrenergic receptor, lax bronchial smooth muscle, not easily transform by monoamine oxidase, MAO, persistent; The edema suppressing endogenous to cause the release of spasm material and endogenous mediator to cause; Strengthen bronchial mucosa epithelial cell fiber movement, accelerate mucus and eliminate, improve bronchial mucosa ciliated epithelial cell and clean up ability, have bronchorelaxing activity; Be applicable to treatment bronchial asthma, chronic asthma bronchitis, obstructive emphysema and other is with pulmonary disease such as bronchospasms clinically.
Terbutaline started clinical trial early than 1967, within 1985, by China's clinical verification, got permission registration, this medicine country's listing application more than 100 so far.In China, the clinical practice of broxaterol (i.e. beta 2-adrenergic receptor agonist) has the history in more than 20 years, is the bronchial spasmolytic agent that current clinical practice is comparatively wide, kind is more.Many experts think that broxaterol is the key agents of relieving asthma acute attack, both can be used for intermittent acute attack, also can be used for the bronchospasm helping the persistence controlling trachea.At present, gone on the market multiple terbutaline sulphate oral formulations (tablet, granule, capsule, oral liquid, aerosol, atomized liquid, inhalation powder spray) both at home and abroad.
Because conventional tablet, granule, capsule are through gastrointestinal Degradation, bioavailability is lower, and not easily swallows, and juvenile crowd and gerontal patient are not too applicable; Also be not easy to patient in the absence of water take.Oral liquid carries inconvenience, is easy to damaged, is also unfavorable for quantitatively taking.Aerosol complicated process of preparation, has troublesome poeration, the shortcomings such as explosive.Powder spray poor stability, cost is higher, and effect duration is short.Atomized liquid is Portable belt not, and treatment time is longer.
Oral instant membrane of the present invention means that the effective ingredient of doses is dispersed in the thin film formulations processed in filmogen.Medicine film is rich in pliability, during use, is directly placed on tongue by medicine film, and medicine film, once contact with saliva of buccal cavity, will dissolve or disintegrate very soon, after swallowing in gastrointestinal tract Fast Stripping.This kind of new formulation can avoid solid preparation to block the danger of throat and the repulsion psychology of patient medication, and does not need drinking-water to take; Be particularly useful for child, old age, be unable to leave the bed and severe disability patient, and people's medication at any time when inconvenience is drunk water.Oral instant film preparation as far back as 2003 in North America listing, preparation has that volume is little, dissolubility is high, rapid-action and can make adult especially child easily grasp the features such as accurate medication dose, by the extensive use of International Pharmaceutical market.As the instant membrane of ondansetron (Zuplenz) of Strative drugmaker exploitation, the diphenhydramine film (TriaminicStripsCough & RunnyNose) of Novartis Co., Ltd's listing, dextromethorphan membrane (TherafluThinStrip).
Patent CN102416167A provides atomized inhalation and the preparation technology thereof of a kind of interferon-ALPHA and terbutaline sulphate.Patent CN1813695A provides a kind of terbutaline sulfate dropping pill and preparation technology thereof.Above-mentioned terbutaline sulphate dosage form, cost is higher, complicated process of preparation, not easily preserves, and is also unfavorable for quantitatively taking.At present, do not have the research and development of terbutaline sulphate oral instant membrane to record for the time being in international market.
Summary of the invention
Object of the present invention is not only provides a kind of agreeable to the taste degree good, meets saliva in the oral cavity and collapses rapidly molten, rapid-action terbutaline sulphate oral instant membrane, for child, old age, to be unable to leave the bed and severe disability patient provides new medication to select; Also provide a kind of volume little, do not need with water delivery service, take, terbutaline sulphate oral instant membrane easy to carry, overcome common listing dosage form and not easily swallow, be difficult to quantitatively, carry inconvenience, the puzzlement of the problems such as complicated operation.
Feature of the present invention is by selecting the macromolecular material of good water solubility as filmogen, ensure that medicine film in the oral cavity can rapid solution; The filmogen of simple use good water solubility can not meet the requirement that oral instant membrane dissolves rapidly in the oral cavity, adds appropriate disintegrating agent, utilize the capillarity of disintegrating agent and expansion can solve this technical barrier in the present invention.
The prescription of terbutaline sulphate oral instant membrane provided by the invention is composed as follows:
Terbutaline sulphate, filmogen, disintegrating agent, filler, sweeting agent, wetting agent, opacifier, coloring agent.
Described filmogen is not only pharmaceutical carrier, also needs by film forming, plays thickening, figuration effect.Its stable in properties, not with drug interaction, also should have good aqueous solubility, be convenient to human body dissolve, absorb.Filmogen of the present invention is selected from hypromellose, xanthan gum, sodium alginate, sodium carboxymethyl cellulose, polyvidone, methylcellulose, hydroxypropyl cellulose, high replaces one in hypromellose or its mixture.
Disintegrating agent has capillarity and expansion, has pore structure after making film drying, forms the capillary channel being easy to moistening, can be spontaneously wet out by water, and after contacting with water, water can enter film inside with capillary channel rapidly, impels the rapid disintegrate of film.Disintegrating agent of the present invention is selected from one in microcrystalline Cellulose, pregelatinized Starch, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium and starch or its mixture.
Opacifier of the present invention can stop light therethrough, and active component is stablized.Gradient color after terbutaline sulphate raw material chance light, the present invention adds opacifier in right amount and improves membrane to the stability of light.Opacifier of the present invention is selected from one in titanium dioxide, iron oxide red, iron oxide yellow, iron oxide brown or its mixture; Preferred titanium dioxide;
Filler of the present invention is selected from one in mannitol, sucrose, glucose, maltose, lactose, sorbitol, xylitol, maltose alcohol, galactitol, erythritol, dextrin, trehalose or its mixture.
Another object of the present invention is to provide a kind of preparation method of terbutaline sulphate oral instant film preparation, comprises the steps:
A mixing, film: take terbutaline sulphate, aspartame, microcrystalline Cellulose, mannitol, titanium dioxide by prescription, with water or glycerine water solution dispersion, add pigment aqueous solution, hydroxypropyl methylcellulose aqueous solution stir;
B film, drying: above-mentioned terbutaline sulphate suspendible glue is applied on flat board uniformly, dry;
C demoulding, cuts into a certain size, packaging.
In said process, described terbutaline sulphate oral instant membrane can be every 1cm
2terbutaline sulphate oral instant membrane containing 1 ~ 30mg terbutaline sulphate in preparation.
Described terbutaline sulphate oral instant membrane, has certain pliability, is convenient to take, sense of discomfort is not had when taking, can simply dissolving or disintegrate in mouth, medicine enters digestive tract with swallowing act and absorbs, dissolubility is high, and in 37 DEG C of water, disintegration time is in 30 seconds, rapid-action.
Advantage of the present invention: 1. mouthfeel is joyful, agreeable to the taste degree is good; 2. in oral cavity, meet saliva collapses rapidly molten, rapid-action; 3. do not need, with water delivery service, to be applicable to child, old age, to be unable to leave the bed and severe disability patient, easy to use; 4. steady quality, is convenient to preserve, carry.
Detailed description of the invention
By following examples terbutaline sulphate oral instant membrane of the present invention done and illustrate further, but scope of the present invention is not limited in these embodiments.So, under method prerequisite of the present invention, all the scope of protection of present invention is belonged to simple modifications of the present invention.
Embodiment 1
Every sheet terbutaline sulphate oral instant membrane sulfur acid terbutaline 2.5mg, consisting of of every 1000 membrane:
Specific operation process: take terbutaline sulphate, aspartame, microcrystalline Cellulose, mannitol, titanium dioxide, after 30% glycerite dispersion, add 0.3% pigment solution, 2% hydroxypropyl methylcellulose solution, limit edged stirs, after stirring, degassed, above-mentioned terbutaline sulphate suspendible glue is coated on flat board uniformly, drying, cutting (2cm × 2cm), obtains terbutaline sulphate oral instant membrane.
This membrane becomes pink, and pliability is good, and entrance dissolves dispersion rapidly, good mouthfeel, and taste is sweet, solution time 25s.
Embodiment 2
Every sheet terbutaline sulphate oral instant membrane sulfur acid terbutaline 2.5mg, consisting of of every 1000 membrane:
Specific operation process: take terbutaline sulphate, aspartame, pregelatinized Starch, trehalose, titanium dioxide, after 30% glycerite dispersion, add 0.3% pigment solution, 1% sodium alginate soln, limit edged stirs, after stirring, degassed, above-mentioned terbutaline sulphate suspendible glue is coated on flat board uniformly, drying, cutting (2cm × 2cm), obtains terbutaline sulphate oral instant membrane.
This membrane pliability is better, and entrance dissolves dispersion rapidly, good mouthfeel, and taste is sweet, solution time 15 ~ 20s.
Embodiment 3
Every sheet terbutaline sulphate oral instant membrane sulfur acid terbutaline 2.5mg, consisting of of every 1000 membrane:
Specific operation process: take terbutaline sulphate, aspartame, low-substituted hydroxypropyl cellulose, maltose alcohol, titanium dioxide, after 30% glycerite dispersion, add 0.3% pigment solution, 0.3% xanthan gum solution, limit edged stirs, after stirring, degassed, above-mentioned terbutaline sulphate suspendible glue is coated on flat board uniformly, drying, cutting (2cm × 2cm), obtains terbutaline sulphate oral instant membrane.
This membrane toughness is better, and entrance dissolves dispersion rapidly, good mouthfeel, and taste is sweet, solution time 15 ~ 20s.
Embodiment 4
Every sheet terbutaline sulphate oral instant membrane sulfur acid terbutaline 2.5mg, consisting of of every 1000 membrane:
Specific operation process: take terbutaline sulphate, aspartame, microcrystalline Cellulose, pregelatinized Starch, maltose alcohol, titanium dioxide, after 30% glycerite dispersion, add 0.3% pigment solution, 1% carboxymethylcellulose sodium solution, limit edged stirs, after stirring, degassed, above-mentioned terbutaline sulphate suspendible glue is coated on flat board uniformly, drying, cutting (2cm × 2cm), obtains terbutaline sulphate oral instant membrane.
This membrane pliability is good, and entrance dissolves dispersion rapidly, good mouthfeel, and taste is sweet, solution time 15 ~ 20s.
Embodiment 5
Every sheet terbutaline sulphate oral instant membrane sulfur acid terbutaline 2.5mg, consisting of of every 1000 membrane:
Specific operation process: take terbutaline sulphate, aspartame, crosslinked carboxymethyl fecula sodium, mannitol, titanium dioxide, after 30% glycerite dispersion, add 0.3% pigment solution, 2% carboxymethylcellulose sodium solution, limit edged stirs, after stirring, degassed, above-mentioned terbutaline sulphate suspendible glue is coated on flat board uniformly, drying, cutting (2cm × 2cm), obtains terbutaline sulphate oral instant membrane.
This membrane toughness is better, and entrance dissolves dispersion rapidly, good mouthfeel, and taste is sweet, solution time 15 ~ 20s.
Claims (4)
1. a terbutaline sulphate oral instant membrane, it is characterized in that every sheet terbutaline sulphate oral instant membrane sulfur acid terbutaline 2.5mg, every 1000 membrane consist of terbutaline sulphate 2.5g, aspartame 2g, pregelatinized Starch 20g, trehalose 4g, glycerol 2.4g, sodium alginate 6.8g, pigment 0.012g, titanium dioxide 2g, essence 4g.
2. a terbutaline sulphate oral instant membrane, it is characterized in that every sheet terbutaline sulphate oral instant membrane sulfur acid terbutaline 2.5mg, every 1000 membrane consist of terbutaline sulphate 2.5g, aspartame 2g, low-substituted hydroxypropyl cellulose 20g, maltose alcohol 4g, glycerol 2.4g, xanthan gum 2.04g, carmine pigment 0.012g, titanium dioxide 2g, essence 4g.
3. a terbutaline sulphate oral instant membrane, it is characterized in that every sheet terbutaline sulphate oral instant membrane sulfur acid terbutaline 2.5mg, every 1000 membrane consist of terbutaline sulphate 2.5g, sucralose 2g, microcrystalline Cellulose 10g, pregelatinized Starch 10g, xylitol 4g, glycerol 2.4g, sodium carboxymethyl cellulose 6.8g, carmine pigment 0.012g, titanium dioxide 2g, essence 4g.
4. a terbutaline sulphate oral instant membrane, it is characterized in that every sheet terbutaline sulphate oral instant membrane sulfur acid terbutaline 2.5mg, every 1000 membrane consist of terbutaline sulphate 2.5g, sucralose 2g, crosslinked carboxymethyl fecula sodium 10g, mannitol 4g, glycerol 2.4g, methylcellulose 13.6g, pigment 0.012g, titanium dioxide 2g, essence 4g.
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| 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 |
| CN104127370B (en) * | 2014-07-31 | 2016-09-14 | 天津市聚星康华医药科技有限公司 | A kind of folic acid oral instant membrane and preparation method thereof |
| CN104224756A (en) * | 2014-09-26 | 2014-12-24 | 天津市聚星康华医药科技有限公司 | Doxazosin mesylate oral instant film and preparation method thereof |
| IL266537B2 (en) | 2016-11-15 | 2023-12-01 | Klaria Pharma Holding Ab | Pharmaceutical formulation |
| GB201709141D0 (en) | 2017-06-08 | 2017-07-26 | Klaria Pharma Holding Ab | Pharmaceutical formulation |
| CN111467365A (en) * | 2019-01-24 | 2020-07-31 | 开封九福来生物技术有限公司 | Oral instant film agent containing dendrobium polysaccharide and preparation method thereof |
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| CN1565429A (en) * | 2003-07-09 | 2005-01-19 | 吴缨 | Instant oral film preparation and its preparation method |
| CN101843581A (en) * | 2009-03-27 | 2010-09-29 | 麦克内尔股份公司 | Has dosage form in many parts oral cavity of organ sensory characteristic |
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|---|---|---|---|---|
| CN1565429A (en) * | 2003-07-09 | 2005-01-19 | 吴缨 | Instant oral film preparation and its preparation method |
| CN101843581A (en) * | 2009-03-27 | 2010-09-29 | 麦克内尔股份公司 | Has dosage form in many parts oral cavity of organ sensory characteristic |
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