CN101352419B - Acebrophylline sugar-free type granular formulation and preparation method thereof - Google Patents
Acebrophylline sugar-free type granular formulation and preparation method thereof Download PDFInfo
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- CN101352419B CN101352419B CN2007100584328A CN200710058432A CN101352419B CN 101352419 B CN101352419 B CN 101352419B CN 2007100584328 A CN2007100584328 A CN 2007100584328A CN 200710058432 A CN200710058432 A CN 200710058432A CN 101352419 B CN101352419 B CN 101352419B
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- acebrophylline
- theophylline
- preparation
- granule
- acebromine
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to an acebromine theophylline sugar-free granular agent and a preparation method thereof, in particular to a granular agent drug which takes the acebromine theophylline as active ingredients and a preparation method thereof, belonging to the western medicine formulation field; the acebromine theophylline sugar-free granular agent consists of the following ingredients by weight in every 1000 dose: 10 to 200g of acebromine theophylline materials, 400 to 4000g of diluents, 0 to 200g of disintegrating agents, 1 to 100g of adhesives, 5 to 300g of corrigents, 0 to 100g of solid fragrances and/or 0 to 200ml of liquid fragrances and 0 to 10g of colorants. The an acebromine theophylline sugar-free granular agent of the invention has the advantages of the use of the novel corrigent and the fragrance covers the self-bitter taste of the acebromine theophylline, avoids the use of sweeteners with a large quantity of sucrose, and the like, reduces the usage of excipients greatly, leads the packing quantity of single dosage of the preparation to be reduced obviously and leads the oral administration and taking of the medicine to be more convenient; simultaneously, the conversion problem of better dosage form of the acebromine theophylline materials is solved, especially the key problem of the stability of the granular agent; the production technique of the preparation ofthe invention is easy to realize production on scale extremely and is suitable to the national situation in China.
Description
Technical field
The present invention relates to a kind of Acebrophylline sugar-free type granular formulation and preparation method thereof, be specifically related to a kind of granules medicine that with Acebrophylline (acebrophylline) is active component and preparation method thereof and belong to the Western medicine preparation field.
Background technology
" chronic obstructive pulmonary disease " is chronic obstructive lung illness (COPD), comprise chronic bronchitis, bronchial asthma and obstructive emphysema etc., its common feature is to have that airway obstruction sexually revises and obstructive ventilatory disorder, causing " expectorant, cough, breathe heavily " three big basic clinical thus, is a kind of destructive pulmonary disease that weakens the patient respiratory function gradually.Many patient Ke Yin expectoration is unfavorable and cause that cough is more than and pant and have much difficulty in healing that patient is agonizing, and quality of life is subjected to very big influence, so can cause cardio-pulmonary function constantly to weaken for a long time, finally causes death.Be to cause dead and disabled principal disease in the global range, ranked the whole world and cause the 4th of dead disease.In China, chronic obstructive pulmonary disease is the fourth-largest reason of dying of illness in city, is the first reason of dying of illness in rural area.This disease causes China's 1,000,000 people's death every year, and causes 5,000,000～1,000 ten thousand people's deformity.At present, China has chronic obstructive pulmonary disease patient 2,700 ten thousand approximately.
Treatment for the patient must be emphasized positive expectoration, removes respiratory secretions effectively, so that the respiratory tract maintenance is unimpeded, can better improve symptom, mitigate the disease.Yet the alternative medicine of clinical treatment chronic obstructive pulmonary disease is few at present, and effect is comparatively single.Common medicine has: 1. anticholinergic agents such as tiotropium bromide etc., this type of medicine suppress parasympathetic nervous system and shrink bronchial effect by the blocking-up cholinoceptor, thus expansion bronchus; 2. β
2Receptor stimulating agent such as methylxanthine, aminophylline etc., this type of medicine directly stimulates airway smooth muscle β
2Receptor, thereby expansion bronchus; 3. thereby glucocorticoid also is used for the chronic obstructive pulmonary disease treatment by suppressing activatory inflammation gene expression blocking-up inflammatory process, but only is used for the severe stage of disease and the COPD patient of acute exacerbation repeatedly, and the patient is to the misgivings of hormone medicine in addition, and its use is limited.
Acebrophylline is the theophylline analog derivative, English name Acebrophylline, molecular formula: C
22H
28Br
2N
6O
5, be the double salt of ambroxol (Ambroxol) with theophylline acetic acid (Acefylline).Ambroxol is the active metabolite of bromhexine, almost has no side effect, and makes the acid mucopolysaccharide fibrous fracture in the sputum, lowers the viscosity of expectorant, can promote asthma patient, particularly gets rid of with the chronic asthmatic bronchitis patient's who glues expectorant sputum.Theophylline acetic acid is phosphodiesterase inhibitor, improves the concentration diastole bronchial smooth muscle of cyclic guanylic acid in the cell, and can strengthen every myotility, also has the cilia activity that strengthens the bronchial mucosa columnar epithelial cell concurrently, helps expectoration.Both have synergism, to breathe heavily, the mitigation of phlegm syndrome shape strengthens greatly.Acebrophylline be widely used in clinical chronic obstructive disease of lung such as bronchial asthma, bronchitis, pharyngitis, sinusitis, and this medicine is safe based on its non-unification drug effect, and toxic and side effects is extremely low, not only can be used for the adult, also can be used safely in the child.
Summary of the invention
The objective of the invention is: providing a kind of is the sugar type granules agent medicine of active component with Acebrophylline (acebrophylline).
Another technical problem that the present invention will solve is: the preparation method that a kind of above-mentioned Acebrophylline granule is provided.
For achieving the above object, the present invention is by the following technical solutions:
Granule of the present invention contains several or whole combination in Acebrophylline active component, dilution filler, disintegrating agent, adhesive, correctives, aromatic, the coloring agent etc., or effective or physiology acceptable auxiliary on some other pharmaceutics.
The Acebrophylline granule, per 1000 doses of components by following weight are formed:
Acebrophylline raw material 10～200g (preferred 20～150g)
Dilution filler 400～4000g (preferred 400～3000g)
Disintegrating agent 0～200g (preferred 0～150g)
Adhesive 1～100g (preferred 1～50g)
Correctives 5～300g (preferred 10～200g)
Aromatic solid type 0～100g (preferred 0～50g)
And/or liquid type 0～200ml (preferred 0～100ml)
Coloring agent 0～10g (preferred 0～5g).
Described dilution filler is used to dilute the dispersion medicine active component, is convenient to the dosage form molding.Be selected from one or more the combination in lactose, mannitol, water soluble starch, the water soluble Beta-cyclodextrin (hydroxypropyl-β-cyclodextrin) etc.Lactose uses as diluent, has the Olibanum flavor simultaneously, thereby has had the effect of aromatic concurrently.Use water soluble starch, cyclodextrin, because of it can increase granule dissolving back solution viscosity, can reduce the sensitivity of taste bud to a certain extent simultaneously, thereby reduce the paralysis sense of patient's medicine when taking itself, improve mouthfeel.The preferred lactose of dilution filler of the present invention is or/and hydroxypropyl-β-cyclodextrin.
Described disintegrating agent is used to regulate the speed that granule dissolves, and also is used for changing dissolving back solution suspension, improves solution appearance, avoids the patient to wrongly take.Be selected from carboxymethyl cellulose (sodium), low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, carboxymethyl starch sodium, polyvinylpolypyrrolidone etc.Preferred low-substituted hydroxypropyl cellulose.
Described adhesive is mainly used in keeps particulate suitable hardness.Be selected from hydroxypropyl methylcellulose, polyvidone, sodium carboxymethyl cellulose etc.Preferred hydroxypropyl methylcellulose.
Described correctives, aromatic can adjust the granule that the patient takes like a shot according to the taste of Acebrophylline medicine itself, especially can be subjected to liking of child simultaneously, and this also is of the present invention one big characteristics.
Described correctives is selected from acesulfame potassium, steviosin, glucide (sodium), aspartame (or aspartame), xylitol, fructose etc., preferred steviosin.
Described aromatic, liquid type are selected from natural or compound essences such as Oleum menthae, Oleum Cinnamomi, Oleum Anisi Stellati, orange peel oil, flavoring banana essence, flavoring pineapple essence, flavoring orange essence, Fructus Citri Limoniae essence, cherry essence, chocolate essence, rose essence; Solid type is the spice of above-mentioned taste.Flavoring banana essence, flavoring orange essence, Fructus Citri Limoniae essence and corresponding spice that preferred child the most likes.The present invention adjusts unique mouthfeel with steviosin and Fructus Musae or Fructus Citri tangerinae odor type correctives, and this also is the present invention one big key problem in technology place.
Described coloring agent can change the color that granule dissolves solution, makes it pleasing outward appearance, and patient takes like a shot, simultaneously can be in use, and avoid the patient to wrongly take or miss.Rationally use as required or do not use, or unite use according to the color matching rule.Be selected from vegetable colour caramel, chlorophyll, amaranth, carmine, lemon yellow, natural or synthetic coloring agent such as indigo, an amount of use.
Also use wetting agent in the pharmacy procedure, be used for moistening medicine and adjuvant powder with the preparation granule, granule does not contain wetting agent after drying.Used wetting agent is selected from the alcohol-water solution of water, alcohol or variable concentrations.Alcohol in the aqueous solution of described alcohol or alcohol is ethanol.
A kind of preparation method of Acebrophylline granule: the Acebrophylline raw material pulverizing is sieved, and dilution filler, disintegrating agent, correctives, aromatic etc. sieve, and preparation adhesive solution (can contain or not contain essence) is standby; Feed intake by prescription, with raw material, dilution filler, disintegrating agent, correctives, aromatic mix homogeneously, after the moistening of adding moistening adhesive, extruding preparation granule, through 50 ℃ of forced air dryings, select particle diameter at the granule that 180 μ m～2000 μ m get through the particle diameter screening, detect back plastic-aluminum packing and make.
The preparation method of another kind of Acebrophylline granule: the Acebrophylline raw material pulverizing is sieved, and dilution filler, disintegrating agent, correctives etc. sieve, and preparation adhesive solution for standby.Feed intake by prescription, with raw material, dilution filler, disintegrating agent, correctives mix homogeneously, after the moistening of adding moistening adhesive, extruding preparation granule through 50 ℃ of forced air dryings, sprays essence, select particle diameter at the granule that 180 μ m～2000 μ m get through the particle diameter screening, detect back plastic-aluminum packing and make.
Recommendation usage and dosage of the present invention is: adult's dosage: oral, and a 100mg (by Acebrophylline), twice of every day; Child dose: oral, a 25～50mg (by Acebrophylline), twice of every day.
The Acebrophylline less stable especially to light and wet poor stability, for granule stability, does not have clear and definite solution.
Sucrose has advantages such as Nantural non-toxic, sweet taste be pure, cheap and easy to get, is widely used in the adjusting of sweet taste, is widely used in several formulations such as oral liquid, granule, chewable tablet.In the invention with corresponding to the prescription of embodiment 1 (numbering 1), adopt the steviosin in sucrose (numbering 2), acesulfame potassium (numbering 3), glucide (sodium) (numbering 4), aspartame (or aspartame) (numbering 5), xylitol (numbering 6), fructose equivalent alternative embodiment 1 prescriptions such as (numberings 7) simultaneously respectively, preparation contains the Acebrophylline granule of different sweeting agents.Above-mentioned sample was placed 10 days down in 60 ℃,, investigated 7 prescription stability of sample with measuring content of medicines and related substance under the condition.60 ℃ of sample stabilities after 10 days the results are shown in following table:
Table 1
Result of study shows that sucrose is applied to the Acebrophylline granule, and stability of drug products is relatively poor, can not effectively guarantee the quality and safety of medicine.Through experimentation, cane sugar substitution agent acesulfame potassium, steviosin, glucide (sodium), aspartame (or aspartame), xylitol, fructose etc. are adopted in invention, guarantee the pure mouthfeel of granule, improve the stability of Acebrophylline simultaneously.Discover especially that with steviosin as the particulate sweeting agent of Acebrophylline, preparation is the most stable.So the alternative sucrose of the preferred steviosin of the present invention as the particulate sweeting agent of Acebrophylline, significantly improves and has guaranteed the particulate stability of Acebrophylline, thereby guarantees that safety of medicine is effective.
Therefore, by the high spot reviews of sweeting agent among the present invention, final the present invention's preparation becomes the sucrose-free sugar type granules, and more highlights following advantage: dental caries low in calories, unlikely, safety non-toxic, sweet taste is pure, mouthfeel is unique.Do not influence blood sugar level, do not cause blood glucose fluctuation, and do not increase the absorption of eater's heat, so the patient can avoid that blood fat raises or the threat of weight increase, thereby the sugared patients' of taboos such as many children, old age and obesity, hypertension, hyperlipidemia, diabetes medication is limited removed.
The present invention selects granule to be applied to this medicine, can realize the actual conversion of social benefit easily with the preparation production technique of routine, has rationally solved problems such as the patient carries, takes, preservation; Very easily accomplish scale production, be fit to China's national situation.Granule is convenient to take, absorbs rapidly, is easy to divided dose, especially can be used as the children kind listing few in number of whole medical market.Provide new selection for solving or alleviating the children respiratory tract diseases symptom.
The particulate invention of Acebrophylline sugar-free, use the novel correctives and the aromatic that substitute sucrose, covered the bitter taste of Acebrophylline itself, avoided the use of sweeting agents such as a large amount of sucrose, significantly reduced the consumption of excipient, single agent Packing Unit of preparation is significantly reduced, make drug administration, carry more convenient.The present invention adjusts unique mouthfeel with steviosin and Fructus Musae or flavoring orange essence, modulates the taste that the child still is grown up and takes like a shot, and has improved patient's compliance.Solved Acebrophylline raw material dosage form transition problem preferably simultaneously, especially as the stable key issue of granule.Preparation of the present invention is produced the worker and is very easily accomplished scale production, and is fit to China's national situation.
The invention will be further described below in conjunction with the specific embodiment; it is not limitation of the invention; according to prior art well known in the art; embodiments of the present invention are not limited to this; therefore all this areas of having done according to the disclosure of invention be equal to replacement, all belong to protection scope of the present invention.
The specific embodiment
Embodiment 1:(is with 1000 doses of calculating)
Acebrophylline 100g
Lactose 1710g
Steviosin 150g
Fructus Citri tangerinae spice 40g
Hydroxypropyl methylcellulose solution is an amount of
Preparation method is: with the Acebrophylline crushing screening, lactose, steviosin, Fructus Citri tangerinae spice etc. sieve, and it is standby as the moistening adhesive to prepare 1.5% hydroxypropyl methylcellulose, 50% alcoholic solution.Feed intake and mix homogeneously by above prescription, after the moistening of adding moistening adhesive, pushed 14 mesh sieves and prepare granule, through 50 ℃ of forced air dryings, the dried particles of particle diameter at 180 μ m～2000 μ m selected in screening, and detection back plastic-aluminum encapsulates makes pouch, promptly.
Embodiment 2:(is with 1000 doses of calculating)
Acebrophylline 150g
Lactose 2000g
Steviosin 150g
Fructus Citri tangerinae spice 40g
Chlorophyll 10mg
Hydroxypropyl methylcellulose solution is an amount of
Preparation method is: with the Acebrophylline crushing screening, lactose, steviosin, Fructus Citri tangerinae spice, chlorophyll etc. sieve, and it is standby as the moistening adhesive to prepare 1.5% hydroxypropyl methylcellulose, 50% alcoholic solution.Feed intake and mix homogeneously by above prescription, after the moistening of adding moistening adhesive, pushed 14 mesh sieves and prepare granule, through 50 ℃ of forced air dryings, the dried particles of particle diameter at 180 μ m～2000 μ m selected in screening, and detection back plastic-aluminum encapsulates makes pouch, promptly.
Embodiment 3:(is with 1000 doses of calculating)
Acebrophylline 50g
Lactose 1370g
Steviosin 100g
Flavoring banana essence 15ml
Chlorophyll 10mg
Hydroxypropyl methylcellulose solution is an amount of
Preparation method is: with the Acebrophylline crushing screening, lactose, steviosin sieve, and preparing 1.5% hydroxypropyl methylcellulose, 50% alcoholic solution, to sneak into flavoring banana essence standby as the moistening adhesive.Feed intake and mix homogeneously by above prescription, after the moistening of adding moistening adhesive, pushed 14 mesh sieves and prepare granule, through 50 ℃ of forced air dryings, the dried particles of particle diameter at 180 μ m～2000 μ m selected in screening, and detection back plastic-aluminum encapsulates makes pouch, promptly.
Embodiment 4:(is with 1000 doses of calculating)
Acebrophylline 50g
Hydroxypropyl-β-cyclodextrin 1250g
Low-substituted hydroxypropyl cellulose 20g
Steviosin 150g
Flavoring orange essence 15ml
Chlorophyll 10mg
Hydroxypropyl methylcellulose solution is an amount of
Preparation method is: with the Acebrophylline crushing screening, hydroxypropyl-β-cyclodextrin, steviosin, chlorophyll etc. sieve, and preparing 1.5% hydroxypropyl methylcellulose, 50% alcoholic solution, to sneak into flavoring orange essence standby as the moistening adhesive.Feed intake and mix homogeneously by above prescription, after the moistening of adding moistening adhesive, pushed 14 mesh sieves and prepare granule, the granule of particle diameter at 180 μ m～2000 μ m selected in 50 ℃ of following forced air dryings, screening, and detection back plastic-aluminum encapsulates makes pouch, promptly.
Embodiment 5:(is with 1000 doses of calculating)
Acebrophylline 100g
Lactose 1250g
Hydroxypropyl-β-cyclodextrin 500g
Steviosin 150g
Flavoring orange essence 15ml
Chlorophyll 10mg
Hydroxypropyl methylcellulose solution is an amount of
Preparation method is: with the Acebrophylline crushing screening, lactose, hydroxypropyl-β-cyclodextrin, steviosin, chlorophyll sieve, and it is standby as the moistening adhesive to prepare 1.5% hydroxypropyl methylcellulose, 50% second alcoholic solution.Feed intake and mix homogeneously by above prescription, after the moistening of adding moistening adhesive, pushed 14 mesh sieves and prepare granule, through 50 ℃ of forced air dryings, screening selects particle diameter at the granule that 180 μ m～2000 μ m get, and sprays the flavoring orange essence mixing, detect back plastic-aluminum encapsulation and make pouch, promptly.
Embodiment 6:(is with 1000 doses of calculating)
Acebrophylline 150g
Lactose 1250g
Hydroxypropyl-β-cyclodextrin 900g
Low-substituted hydroxypropyl cellulose 50g
Steviosin 150g
Flavoring orange essence 20ml
Chlorophyll 10mg
Hydroxypropyl methylcellulose solution is an amount of
Preparation method is: with the Acebrophylline crushing screening, lactose, hydroxypropyl-β-cyclodextrin, low-substituted hydroxypropyl cellulose, steviosin etc. sieve, and it is standby as the moistening adhesive to prepare 1.5% hydroxypropyl methylcellulose, 50% alcoholic solution.Feed intake and mix homogeneously by above prescription, after the moistening of adding moistening adhesive, pushed 14 mesh sieves and prepare granule, through 50 ℃ of forced air dryings, the granule of particle diameter at 180 μ m～2000 μ m selected in screening, sprays flavoring orange essence, mixing detects back plastic-aluminum encapsulation and makes pouch, promptly.
In conjunction with the embodiments, the present invention, has also further done sensory evaluation, the test of pesticide effectiveness and has been had a try with preliminary volunteer and test except the conventional quality research of pharmacy the Acebrophylline granule.
Embodiment 7: the sensory evaluation of embodiment 1
One. method:
Sensory evaluation is product quality evaluation methodology the most intuitively, rely on vision, olfactory sensation, the sense of taste and sense of touch to wait and identifies the particulate mode of appearance of Acebrophylline, color and luster, abnormal smells from the patient and hardness etc., macro-indicators is not met the product quality claimer distinguish and controlled.The present invention requires to be color and luster, even particle size unanimity to particulate sense organ, fresh free from admixture, and hardness is suitable, no loose, caking phenomenon, fragrant pleasant maybe must not have an abnormal flavour stink, and granule 10g can dissolve and not have foreign body fully among the hot water 200ml in 5 minutes.
Two. result: see Table 2:
Table 2: sensory evaluation result
Embodiment 5: the test of pesticide effectiveness of embodiment 1
One. material and method:
1. test objective: the calibrating Acebrophylline is particulate relievings asthma, phlegm-dispelling functions
2. be subjected to the reagent product: the Acebrophylline granule
Lot number: 050216
Specification: 100mg (by Acebrophylline)
Cavia porcellus gavages usefulness: 0.8, and 1.2mg/ml; Mouse gavaging is used: 1.3, and 2.0mg/ml
Compound method: water-soluble solution
Animal: source: Tianjin Inst. of Materia Medica Animal House
The quality certification: Tianjin moving 001
Kind strain: Cavia porcellus (body weight is seen below)
The ICR mice
Body weight: 20 ± 2 (mices)
Sex: male and female half and half
Each treated animal number (seeing below)
3. method:
(1) influence of Acebrophylline granule dialogue three rare (LTD4) the Cavia porcellus asthma of bringing out
Get Cavia porcellus childhood (body weight＜200g, male and female dual-purpose: 32, be divided into 4 groups at random, 8 every group.The blank group is irritated stomach normal saline (20ml/kg/ time), and Acebrophylline granule I, II group is irritated stomach Acebrophylline 8,12mg/kg/ time; Positive controls theophylline 1.2mg/kg/ time.The previous day is drawn the method for breathing heavily (draw and breathe heavily device: constitute the fog chamber by air compressor, aerosol shower nozzle, hydrargyrum manometer, 4L glass bell jar) with medicine in administration, Cavia porcellus is put into bell jar respectively, spray into 100 μ g/ml LTD4 (LTD4 lot numbers: 045889 with 400mmHg pressure, by PENINSULALABORATORIES, INC. provides) 15 minutes.Take out, observe drawing of Cavia porcellus and breathe heavily incubation period (beginning to asthma attack, until time that tic is fallen from spraying), screening is drawn and is breathed heavily incubation period＜120 second person.Eligible is had a rest and is used for experiment more than 24 hours.Next day grouping, gastric infusion respectively, medication is drawn with same method, the same terms test after 45 minutes and is breathed heavily incubation period, surpasses 360 seconds persons incubation period and then calculates with 360 seconds persons.Relatively change between each group and before and after the medication.
(2) the Acebrophylline granule is to the influence of the phenol red excretion amount of mice
Get 40 of ICR mices, be divided into 4 groups at random, 10 every group.The blank group is pressed 20ml/kg and is irritated the stomach normal saline, and Acebrophylline granule I, II group is irritated stomach 13,20mg/kg Acebrophylline granule, and positive controls is irritated stomach bromhexine 2.1mg/kg.The 1st 2 the skys, afternoon respectively irritate stomach once, half an hour after the administration in the morning in the 3rd day, mouse peritoneal is injected 5% phenol red normal saline solution 10ml/kg, injected back 30 minutes, the execution mice (fasting 8 before the experiment---12 hours), separate trachea, get the trachea of equal length, put into the small beaker that fills 1ml normal saline and 0.1ml, 1mol/LNaOH, vibrated 30 minutes, 546nm wavelength place colorimetric is converted out phenol red amount under phenol red standard curve.Compare with matched group, the positive group of contrast.
(3) volunteer is subjected to the examination situation
5 bronchial asthma patients are tried granule of the present invention voluntarily, and the patient is in treatment inactive any other suppressing panting calming medicine in 8 o'clock evenings of the previous day, and examined 8 o'clock inferior mornings.Take 1 bag of Acebrophylline granule (100mg Acebrophylline) earlier, do pulmonary function test after 2 hours.Later every day 2 times, each 1 bag, observe 3 days, 7 days continuously, and do pulmonary function test.
The variation of lung function index before and after observation is taken medicine.3 indexs of pulmonary function comprise:
(1) vital capacity (VC): the maximum dark air-breathing slow maximum tolerance of exhaling and to breathe out.
(2) forced vital capacity (FVC): make the tolerance that maximum forced expiration can be breathed out after air-breathing deeply.
(3) first seconds timed vital capacity (FEV
1): make maximum forced expiration, the tolerance that in first second, can breathe out after air-breathing deeply.Its value reduces during airway obstruction.
Two. the result:
1. the influence of Acebrophylline granule dialogue three rare (LTD4) the Cavia porcellus asthma of bringing out: see Table 3.
Table 3: Shuchuanping draws the influence of breathing heavily (n=8, mean ± SD) to Cavia porcellus LTD4
Compare △ p＜0.05, △ △ p＜0.01 with Acebrophylline granule II group; With Acebrophylline granule I group comparison ▲ p＜0.05, ▲ ▲ p＜0.01; Compare with the blank group ◆ ◆＜0.01
Two. the particulate phlegm-dispelling functions of Acebrophylline: see Table 4.
Table 4 Acebrophylline granule is to the influence of the phenol red excretion amount of air flue (n=10, mean ± SD)
Compare △ △ p＜0.01 with Acebrophylline granule II group; With Acebrophylline granule I group comparison ▲ p＜0.05, ▲ ▲ p＜0.01; Compare with the blank group ◆ ◆＜0.01
3. volunteer is subjected to the examination situation
The oral Acebrophylline granule of all volunteers is after 2 hours, and its VC, FVC, FEV1 are all than increasing before the medication.After 3 days and 7 days, its lung function index takes an evident turn for the better, and clinical symptoms is obviously improved.
Four, conclusion
1. Acebrophylline 8, gavage Cavia porcellus 12mg/kg/ time, can obviously suppress Cavia porcellus asthma attack that LTD4 brings out and prolongation and draw and breathe heavily incubation period.
2. Acebrophylline 13, and 20mg/kg gavages mice, can obviously increase airway of mice phenol red output, have the respiratory tract of promotion secretory action.
3. experimental result shows that the Acebrophylline granule has possessed the dual function of relievining asthma, eliminate the phlegm, and curative effect is better.
Claims (6)
1. Acebrophylline granule, it is characterized in that: per 1000 doses of components by following weight are formed:
Acebrophylline raw material 10～200g
Dilution filler 400～4000g
Disintegrating agent 0～200g
Adhesive 1～100g
Correctives 5～300g
Aromatic solid type 0～100g
And/or liquid type 0～200ml
Coloring agent 0～10g
Wherein, described correctives is: acesulfame potassium, steviosin, glucide (sodium), aspartame, xylitol or fructose;
Described dilution filler is selected from one or more in lactose, mannitol, water soluble starch, the HP-.
2. Acebrophylline granule according to claim 1 is characterized in that: per 1000 doses of components by following weight are formed:
Acebrophylline raw material 20～150g
Dilution filler 400～3000g
Disintegrating agent 0～150g
Adhesive 1～50g
Correctives 10～200g
Aromatic solid type 0～50g
And/or liquid type 0～100ml
Coloring agent 0～5g.
3. Acebrophylline granule according to claim 1 and 2 is characterized in that: described disintegrating agent is selected from carboxymethyl cellulose (sodium), low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, carboxymethyl starch sodium or polyvinylpolypyrrolidone.
4. Acebrophylline granule according to claim 1 and 2 is characterized in that: described adhesive is selected from hydroxypropyl methylcellulose, polyvidone or sodium carboxymethyl cellulose.
5. Acebrophylline granule according to claim 1 and 2 is characterized in that: described aromatic is selected from Oleum menthae, Oleum Cinnamomi, Oleum Anisi Stellati, orange peel oil, flavoring banana essence, flavoring pineapple essence, flavoring orange essence, Fructus Citri Limoniae essence, cherry essence, chocolate essence or rose essence.
6. Acebrophylline granule according to claim 1 and 2 is characterized in that: described coloring agent is selected from vegetable colour caramel, chlorophyll, amaranth, carmine, lemon yellow or indigo.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100584328A CN101352419B (en) | 2007-07-26 | 2007-07-26 | Acebrophylline sugar-free type granular formulation and preparation method thereof |
Applications Claiming Priority (1)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107970214A (en) * | 2012-11-30 | 2018-05-01 | 葛兰素史克公司 | New pharmaceutical composition |
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| KR101506626B1 (en) * | 2013-12-26 | 2015-03-30 | 현대약품 주식회사 | Sustained-release pharmaceutical composition comprising acebrophylline and a hydrophobic material |
| KR101506627B1 (en) * | 2013-12-26 | 2015-03-30 | 현대약품 주식회사 | Sustained-release pharmaceutical composition comprising acebrophylline and a hydrophilic material |
| CN104771358A (en) * | 2014-01-14 | 2015-07-15 | 江苏柯菲平医药股份有限公司 | Acebrophylline injection and preparation method thereof |
| CN105520944A (en) * | 2016-01-04 | 2016-04-27 | 石家庄学院 | Stable theophylline acetic acid ambroxol solution for inhalation |
-
2007
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Non-Patent Citations (4)
| Title |
|---|
| Giovanni Agliati."Acebrophylline in the treatment of chronic obstructivepulmonary disease".Current Therapeutic Researchvol 56 no 2.1995,vol 56(no 2),169. |
| Giovanni Agliati."Acebrophylline in the treatment of chronic obstructivepulmonary disease".Current Therapeutic Researchvol 56 no 2.1995,vol 56(no 2),169. * |
| 毕殿洲.药剂学 第4版.人民卫生出版社,2000,297. |
| 毕殿洲.药剂学 第4版.人民卫生出版社,2000,297. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107970214A (en) * | 2012-11-30 | 2018-05-01 | 葛兰素史克公司 | New pharmaceutical composition |
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