CN101214227A - Ambroxol hydrochloride dry powder inhalant and preparation thereof - Google Patents
Ambroxol hydrochloride dry powder inhalant and preparation thereof Download PDFInfo
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Abstract
The present invention belongs to the medication technical field and discloses hydrochloric ambroxol dry powder inhalant and a preparation method thereof. The hydrochloric ambroxol dry powder inhalant consists of hydrochloric ambroxol, dispersion flow aid and thinner, the weight percentage of which is 60 percent to 90 percent of the hydrochloric ambroxol, 10 percent to 30 percent of the dispersion flow aid and 0 percent to 40 percent of the thinner. The present invention comprises the following steps that the hydrochloric ambroxol or the hydrochloric ambroxol and the dispersion flow aid or the hydrochloric ambroxol, the dispersion flow aid and the thinner are processed for spray drying to obtain powder body which is collected into a glutin or plastic capsule or into an aluminum-plastic bubble cap or is contained inside a large dosage dry powder absorbing device as the storehouse form. The present invention adopts the dry powder inhalant to ensure that the hydrochloric ambroxol is directly absorbed into respiratory tract and lung by a medication device to act directly inside the respiratory tract, so as to achieve the purpose of the safe and targeting treatment with quick result and high efficiency.
Description
Technical field
The invention belongs to medical technical field, relate to ambroxol hydrochloride dry powder inhalant and preparation method thereof.
Background technology
Respiratory system disease is one of disease kind of being familiar with of people, shows according to the relevant statistics of health ministry, and the prevalence of China's respiratory system disease is about about 6.94%, and promptly the whole nation has more than 8,000 ten thousand people to suffer from respiratory system disease every year.And from the age, an old Shaozheng is the age bracket occurred frequently of respiratory system disease.Respiratory system disease accounts for medical patient's 1/4, brings spirit and sensual misery to patient, and in China's demography, respiratory system disease is second cause of the death, but alternative clinically medicine is also few and onset is slower.Therefore timely proper treatment is significant to improving patients ' life quality.
Ambroxol hydrochloride be bromhexine hydrochloride at the intravital metabolite of people, be mucolytic agent, act on stronger than bromhexine.Can increase the secretion of respiratory mucosa serous gland, reduce the mucous gland secretion, the mucopolysaccharide fiber in minimizing and the fracture sputum reduces sputum viscosity, and the sputum attenuation is easy to expectoration.This medicine also can activate alveolar epithelium II type cell synthetic surface active substance, lowers mucous adhesive force, improves the conveying of the mucus in cilium and fibre-less district at respiratory tract, discharges in order to sputum, reaches the effect of cleaning up respiratory mucosa, directly protects pulmonary function.In addition, this medicine has certain antitussive action, and antitussive effect is equivalent to 1/2 of codeine.
Ambroxol hydrochloride from the beginning of the eighties after Germany listing, go on the market one after another in Japan, European many countries.The kind of preparation is also more, and at present domestic have dosage forms such as the tablet of comprising, capsule, oral liquid, slow releasing capsule, aerosol to go on the market.The patent of domestic ambroxol hydrochloride has more than 30 piece, wherein relates to dosage forms such as tablet, capsule, oral liquid, slow releasing capsule, aerosol.The oral formulations onset is slow, and whole body plays a role, and side effect is big, but easy to use.Though injection can directly be imported blood of human body with medicine, onset is very fast relatively, but still whole body plays a role, and side effect is big, brings certain painful and inconvenient simultaneously to the patient.Aerosol contains freon, will cause atmospheric pollution, and simultaneously aerosol exists respiratory tract and patient to use the collocation problem, even through instructing 30% the patient of also having an appointment correctly not use, be unfavorable for bringing into play therapeutical effect.
Summary of the invention
The weak point that the oral formulations of purpose of the present invention ambroxol hydrochloride at above-mentioned prior art, injection and aerosol exist, the spy provide a kind of easy to use, do not contain that propellant, medicine are powdered, good stability, interference factor is few, safety good, rapid-action, toxic and side effects is little, patient's compliance strong, medicine directly acts on lesions position and reaches rapid treatment Foradil Aerolizer formoterol fumarate.Ambroxol hydrochloride dry powder inhalant of the present invention is on the basis of aerosol inhalation solution agent, a kind of novel form that the achievement in research of integrated application powder technology grows up.
The objective of the invention is to be achieved through the following technical solutions:
Ambroxol hydrochloride dry powder inhalant, be to be the spray powder end of 1-5 μ m ambroxol hydrochloride and fluidizer or ambroxol hydrochloride and fluidizer and diluent with particle diameter, place in the gelatin of powder inhaler or plastic capsule or the bubble-cap or be included in the multiple dose powder inhaler with the form of single dose 15-30mg to form with depot forms.
The present invention is made up of ambroxol hydrochloride, dispersion fluidizer and diluent, and its percentage by weight is: ambroxol hydrochloride 60%-90%, disperse fluidizer 10%-30%, diluent 0-40%.
Described fluidizer is the amino acids leucine, isoleucine, one or more in valine or the threonine.The diluent of being addressed is lactose, mannitol, glucose, sucrose or their mixture.Described ambroxol hydrochloride dry powder inhalant is to place capsule No. 3.
The powder of ambroxol hydrochloride dry powder inhalant adopts following technology to realize:
Ambroxol hydrochloride is dissolved in the distilled water with different mixed respectively with fluidizer and diluent, sodium hydroxide with 0.1mol/L is transferred pH to 6.0, adopts identical drying process with atomizing parameter (inlet temperature, hydrojet speed, whiff pressure, aspiration) preparation ambroxol hydrochloride dry powder inhalant behind 0.2 μ m filtering with microporous membrane.The gained powder is filled in No. 3 capsules.
Ambroxol hydrochloride dry powder inhalant of the present invention has the following advantages:
The present invention adopts Foradil Aerolizer formoterol fumarate, makes ambroxol hydrochloride directly arrive lesions position through doser, thereby reaches safety, targeting, quick-acting, therapeutic purposes efficiently.
Foradil Aerolizer formoterol fumarate is on the basis of aerosol, for overcoming the shortcoming of aerosol, a kind of novel form that the achievement in research of integrated application powder technology grows up.Foradil Aerolizer formoterol fumarate is easy to use, do not contain propellant, medicine is powdered, good stability, interference factor is few, safety good, thereby is subject to people's attention day by day.The great advantage of Foradil Aerolizer formoterol fumarate is that patient's inspiratory airflow is that powder enters intravital unique power, does not have suction dyssynergia, especially is fit to old man and child and uses.With oral formulations, injection and aerosol are compared, Foradil Aerolizer formoterol fumarate has following advantages: (1) patient sucks medicated powder, there is not the no propellant freon of administration coordinated difficulty (2), can avoid can capsule or form of vesicles administration to atmospheric pollution and respiratory tract (3) medicine, dosage is accurate, no overdose administration danger (4) does not contain solvents such as antiseptic and ethanol, the no first pass effect of hepar of the no gastrointestinal tract Degradation of pathological changes mucosa nonirritant (5) (6) (7) drug targeting is made good use of, rapid-action (8) patient's compliance is good, carry out the medicine of patient (a 9) local action of long-term treatment especially for need, dosage obviously reduces, toxic and side effects is little, directly enters the body circulation after safety good (10) drug absorption, can reach the purpose of whole body therapeutic.
Description of drawings
Fig. 1 is the concentration (n=3) of ambroxol hydrochloride in the lung rete malpighii of microdialysis technical measurement after the trachea administration
Fig. 2 is the concentration (n=3) of ambroxol hydrochloride in the lung rete malpighii of microdialysis technical measurement behind the intravenously administrable
Fig. 3 is a concentration (n=3) of directly measuring the ambroxol hydrochloride in the blood after vein and the trachea administration
The specific embodiment
The present invention is done the detailed description in a nearly step below in conjunction with embodiment:
Ambroxol hydrochloride is dissolved in the 100mL distilled water with different mixed respectively with fluidizer and diluent, sodium hydroxide with 0.1mol/L is transferred pH to 6.0, adopts identical drying process with atomizing parameter (110 ℃, hydrojet speed 1.8mL min behind 0.2 μ m filtering with microporous membrane
-1, pump pressure 170KPa, throughput be 0.7m
3Min
-1) the preparation ambroxol hydrochloride dry powder inhalant, spray powder is filled in No. 3 capsules.
Present embodiment adopts the SD-1000 spray dryer of Japanese EYELA company.
Ambroxol hydrochloride 2.5g (89.3%) mixed with leucine 0.3g (10.7%) be dissolved in the 100mL distilled water, sodium hydroxide with 0.1mol/L is transferred pH to 6.0, carry out spray drying behind 0.2 μ m filtering with microporous membrane, adopting process parameter inlet temperature is 110 ℃, hydrojet speed 1.8mLmin
-1, pump pressure 170KPa, throughput be 0.7m
3Min
-1The preparation ambroxol hydrochloride dry powder inhalant is filled in spray powder in No. 3 capsules.
Present embodiment adopts the SD-1000 spray dryer of Japanese EYELA company.
Ambroxol hydrochloride 2.5g (83.3%) mixed with leucine 0.5g (16.7%) be dissolved in the 100mL distilled water, sodium hydroxide with 0.1mol/L is transferred pH to 6.0, carry out spray drying behind 0.2 μ m filtering with microporous membrane, adopting process parameter inlet temperature is 110 ℃, hydrojet speed 1.8mLmin
-1, pump pressure 170KPa, throughput be 0.7m
3Min
-1The preparation ambroxol hydrochloride dry powder inhalant is filled in spray powder in No. 3 capsules.
Embodiment 3
Present embodiment adopts the SD-1000 spray dryer of Japanese EYELA company.
Ambroxol hydrochloride 2.5g (71.4%) mixed with leucine 1g (28.6%) be dissolved in the 100mL distilled water, sodium hydroxide with 0.1mol/L is transferred pH to 6.0, carry out spray drying behind 0.2 μ m filtering with microporous membrane, adopting process parameter inlet temperature is 110 ℃, hydrojet speed 1.8mLmin
-1, pump pressure 170KPa, throughput be 0.7m
3Min
-1The preparation ambroxol hydrochloride dry powder inhalant is filled in spray powder in No. 3 capsules.
Embodiment 4
Present embodiment adopts the SD-1000 spray dryer of Japanese EYELA company.
Ambroxol hydrochloride 2.5g (71.4 2%), leucine 0.5g (14.39%) mixed with mannitol 0.5g (14.39%) be dissolved in the 100mL distilled water, sodium hydroxide with 0.1mol/L is transferred pH to 6.0, carry out spray drying behind 0.2 μ m filtering with microporous membrane, adopting process parameter inlet temperature is 110 ℃, hydrojet speed 1.8mLmin
-1, pump pressure 170KPa, throughput be 0.7m
3Min
-1The preparation ambroxol hydrochloride dry powder inhalant is filled in spray powder in No. 3 capsules.
Present embodiment adopts the SD-1000 spray dryer of Japanese EYELA company.
Ambroxol hydrochloride 2.5g (62.5%), leucine 0.5g (12.5%) mixed with mannitol 1g (25%) be dissolved in the 100mL distilled water, sodium hydroxide with 0.1mol/L is transferred pH to 6.0, carry out spray drying behind 0.2 μ m filtering with microporous membrane, adopting process parameter inlet temperature is 110 ℃, hydrojet speed 1.8mLmin
-1, pump pressure 170KPa, throughput be 0.7m
3Min
-1The preparation ambroxol hydrochloride dry powder inhalant is filled in spray powder in No. 3 capsules.
Present embodiment adopts the SD-1000 spray dryer of Japanese EYELA company.
Ambroxol hydrochloride 2.5g (55.56%), leucine 0.5g (11.11%) mixed with mannitol 1.5g (33.33%) be dissolved in the 100mL distilled water, sodium hydroxide with 0.1mol/L is transferred pH to 6.0, carry out spray drying behind 0.2 μ m filtering with microporous membrane, adopting process parameter inlet temperature is 110 ℃, hydrojet speed 1.8mLmin
-1, pump pressure 170KPa, throughput be 0.7m
3Min
-1The preparation ambroxol hydrochloride dry powder inhalant is filled in spray powder in No. 3 capsules.
The method of inspection:
1. deliquescent mensuration
Get 2 of Foradil Aerolizer formoterol fumarate capsules, open softgel shell, the content powder is put into the test tube with ground stopper that 2ml water is housed, jolting 1min observes its dissolving situation.If powder can dissolve and the solution clarification, dissolubility is qualified.If show muddy, then dissolubility is defective.
2. hygroscopic mensuration
Drawing moist test direction principle (two appendix XIX of Chinese Pharmacopoeia version in 2005 J) according to medicine measures.
Medicine draw the moist characteristic that is meant this material absorbing moisture under uniform temperature and damp condition.This law is only as statement medicine hygroscopic a kind of indication, is applicable to that Chinese Pharmacopoeia records and satisfies the medicine that loss on drying under this kind text item or moisture limit require.Also can be used as simultaneously medicine and select the suitable packing and the reference of storage requirement.
Concrete assay method is as follows:
(1) gets a certain amount of test sample and put a known precision (m that weighs
1) tool plug glass weighing botle (external diameter is 50mm, and height is 15mm) in, the precision (m that weighs
2).
(2) uncovered 25 ℃ ± 1 ℃ suitable thermostatic drier (ammonium chloride or ammonium sulfate saturated solution are placed in the bottom) or the growth cabinet (design temperature is 25 ℃ ± 1 ℃) of placing of weighing botle, relative humidity is in (80% ± 2%).
(3) placed 24 hours
(4) build the lid of weighing botle, precision weigh (m)
(5) draw moist feature description and draw defining of wet weightening finish
Have draw moist: drawing wet weightening finish and being not less than 15%.
Have draw moist: drawing wet weightening finish less than 15% and be not less than 2%.
Slightly draw moist: draw wet weightening finish less than 2% and be not less than 0.2%.
Deliquescence: absorb enough water and divide formation liquid.
3. the mensuration of water content
Adopt thermogravimetric analysis to measure the moisture of powder spray.About 5mg sample is put into the aluminum crucible, begin to heat up from 25 ℃, keep 10min during to 105 ℃, continue to be warming up to 200 ℃ again, programming rate is 10 ℃/min.Recently represent moisture to subtract the weight loss percentage.
4. powder morphology is observed
By scanning electron microscopic observation the appearance form of powder particle.Sample is dispersed on the double faced adhesive tape, behind the metal spraying, observes down in scanning electron microscope.Accelerating potential is 15kV, and amplification is 1000～4000 times.
5. tap density and particle size determination
The tap density of powder is measured according to the method for British Pharmacopoeia: after reading the first volume of powder in the graduated cylinder, the concussion graduated cylinder of machinery up to there not being further change in volume, reads final volume.With the heavy tap density that promptly gets powder of comparing with final volume of powder.
Measure the particle diameter of powder sample with laser granulometry, this method can be measured the volumetric diameter Dv of particle, but will be used for the evaluation of dynamic particle, also need adopt aerodynamic size (aerodynamicdiameter, Da), the relation of two kinds of particle diameters is as shown in the formula institute:
Da＝(ρ/ρ
1)
1/2·Dv
Wherein ρ is a Particle Density, ρ
1=1g/cm
3, Dv is the mean diameter of particle.The ρ value can estimate that ρ is about 1.26 times of tap density by tap density, can draw the Da of each powder body by the measurement result of tap density and mean diameter.It is generally acknowledged that Da is suitable for pulmonary administration at the particle of 1-5 μ m.
6. mobile
The method of estimating powder flowbility is more, selects for use at this and represents its flowability angle of repose.This product powder is fallen into the central part of disk slowly, equably from the height of about 4～5cm, make powder body form cone, when powder stops to feed in raw material when the powder body hypotenuse freely falls along disk border, measure and calculate behind the height of powder layer and the disc radius and get.
7. the mensuration of Emptying Rate
Measure the Emptying Rate of this product with reference to method under the powder spray item among Chinese Pharmacopoeia version appendix in 2005 IL.Get 10 of this product capsules, the fixed (W of accurate respectively title
1), place in the suction apparatus by grain, with the capsule punching, again suction apparatus is linked to each other with the deposition ratio in the effective position device, use the air-flow of per minute 60L ± 5L to aspirate 4 times, each 1.5 seconds, claim to decide weight (W
2), with the clean residual content of little grooming, divide another name to decide softgel shell weight (W again
3), obtain every Emptying Rate with following formula:
[(W
1-W
2)/(W
1-W
3)]×100％
8. the mensuration of deposition ratio in the effective position
Measure according to Foradil Aerolizer formoterol fumarate droplet measure of spread method (two appendix XH of Chinese Pharmacopoeia version in 2005).
Get 1 of test sample capsule; put in the suction apparatus; with finger pressing device both sides button; the capsule both sides are punctured, open vacuum pump, suction apparatus is horizontal close proximity through suitable rubber interface with the simulation B of throat; take off inhaler after 10 seconds. repeat aforesaid operations; measure 10 or 20 capsules altogether by the regulation under the kind item, close pump, detaching device.
With the inside and outside wall of conduit of filter, F interface and conduit lower taper bottle behind the blank acceptable solution cleaning aforesaid operations and the surface of pad ridge, acceptable solution among washing liquid and the second level distribution bottle H merges, after quantitatively being diluted to certain volume, measure by the method under the kind item, the gained result is divided by 10 or 20, and compare with indicating content, be medicine droplet abundance.
Table 1: result of the test
| Embodiment | Dissolubility | Draw moist % | Water content | Form | Particle diameter (μ m) | Angle of repose (°) | Emptying Rate | Deposition % | |
| 1 | Qualified | 2.3 | 5.5 | Gauffer | 2.34 | 42.3 | 95.6 | 34.5 | |
| 2 | Qualified | 2.9 | 5.2 | Gauffer | 2.56 | 40.6 | 97.8 | 46.7 | |
| 3 | Qualified | 2.1 | 5.6 | Gauffer | 2.78 | 43.8 | 92.3 | 42.5 | |
| 4 | Qualified | 3.4 | 4.6 | Spherical | 3.95 | 37.6 | 95.5 | 30.8 | |
| 5 | Qualified | 3.0 | 4.7 | Spherical | 3.25 | 29.5 | 97.3 | 32.3 |
| 6 | Qualified | 3.5 | 4.8 | Spherical | 3.21 | 34.7 | 92.6 | 33.6 |
Conclusion: the present invention can obtain to be fit to the ambroxol hydrochloride dry powder inhalant of pulmonary administration.
Embodiment 8
Dry powder detects the respiratory mucosa zest
(1) test objective
Determine the influence of single or multiple administration to rat lungs and tracheal tissue.
(2) test material
Animal subject: SD rat, body weight 250-300g, experimental animal source: provide by zoopery center, medicine University of Science and Technology, Shenyang.
Be subjected to reagent product: embodiment 5 ambroxol hydrochloride dry powder inhalants
(3) test method
Behind the rat etherization, give ambroxol hydrochloride dry powder inhalant by trachea.Single-dose, medicine group and give each 8 of every group of vehicle group, every rat of administration group gives ambroxol hydrochloride powder inhalant 20mg/kg respectively, and every rat of vehicle group gives except that principal agent accordingly excipient respectively and dissects after 24 hours.Multiple dosing, administration group and give each 8 of every group of vehicle group, give once every day, and administered dose is with the single-dose group, and continuous seven days, the general situation of observing animal every day, in the time, dissect, and takes out lung and the trachea of every group every animal, carries out gross examination of skeletal muscle.Relatively administration group vehicle group lung surface has or not petechia, pulmonary atelectasis or emphysema; Tunica mucosa tracheae has or not hyperemia, phenomenon such as red.
(4) result of the test
Table 2: single-dose symptom variation
| Time (h) | Breathe | Gastrointestinal tract | Topography (lung and trachea) | |
| Administration group (n=8) | 0 | Normally | Normally | - |
| 4 | Normally | Normally | - | |
| 8 | Normally | Normally | - | |
| 24 | Normally | Normally | No significant change | |
| Vehicle group (n=8) | 0 | Normally | Normally | - |
| 4 | Normally | Normally | - | |
| 8 | Normally | Normally | - | |
| 24 | Normally | Normally | No significant change |
Table 3: multiple dosing symptom variation
| Time (my god) | Breathe | Gastrointestinal tract | Topography (lung and trachea) | |
| Administration group (n=8) | 0 | Normally | Normally | - |
| 1 | Normally | Normally | - | |
| 2 | Normally | Normally | - | |
| 3 | Normally | Normally | - |
| 4 | Normally | Normally | - | |
| 5 | Normally | Normally | - | |
| 6 | Normally | Normally | - | |
| 7 | Normally | Normally | - | |
| 8 | Normally | Normally | No significant change | |
| Vehicle group (n=8) | 0 | Normally | Normally | - |
| 1 | Normally | Normally | - | |
| 2 | Normally | Normally | - | |
| 3 | Normally | Normally | - | |
| 4 | Normally | Normally | - | |
| 5 | Normally | Normally | - | |
| 6 | Normally | Normally | - | |
| 7 | Normally | Normally | - | |
| 8 | Normally | Normally | No significant change |
Morphology: single and multiple dosing group there is no macroscopic pathological changes.Rat is put to death the back and dissects, and takes out trachea and lung, gross examination of skeletal muscle, and administration group and vehicle group there is no trachea hyperemia, redness; Phenomenons such as pulmonary atelectasis, emphysema and petechia.
(5) conclusion
Rat is carried out the irritation test that single and multiple dosing in the trachea carry out lung and trachea, do not see irritant reaction relevant and symptom with medicine.
Embodiment 9
Ambroxol hydrochloride pulmonary targeting efficient and pharmacokinetic Study
(1) test objective
Rat is given respectively and ambroxol hydrochloride inhalant and intravenous injection ambroxol hydrochloride, measures the drug level in lung rete malpighii and the blood, thereby investigates targeting efficient and the interior pharmacokinetics of body after the administration of ambroxol hydrochloride inhalant trachea.
(2) test material
Animal subject: SD rat, body weight 250-300g, experimental animal source: provide by Shenyang Pharmaceutical University zoopery center.
Be subjected to reagent product: embodiment 5 ambroxol hydrochloride dry powder inhalants and self-control ambroxol hydrochloride injection (3) test method
All rats draw tantalum (1.2g/kg) lumbar injection to anaesthetize with the 0.2g/mL crow, are placed under the infrared lamp, keep body temperature at 37 ℃.Get 12 rats and be divided into two groups, one group by trachea give with ambroxol hydrochloride dry powder inhalant (TA) (20mg/kg), the ambroxol hydrochloride (i.v.) with same dose is given in another group intravenous injection.Each group is divided into two groups more respectively, one group of concentration by microdialysis technical measurement lung rete malpighii, and another group is directly measured the drug level in the blood.
Rat give respectively with ambroxol hydrochloride dry powder inhalant and intravenous injection ambroxol hydrochloride after, every group of Mus of getting half used the concentration of microdialysis technical measurement ambroxol hydrochloride at the lung rete malpighii, by the tracheostoma technology microdialysis probe is implanted the lung rete malpighii, use of the speed perfusion of Ringer ' s liquid with 4 μ L/min.Every 15min collects a sample, carries out assay then.Second half animal eye socket of every group is got the drug level of directly measuring behind the blood in the blood, and sampling time point is respectively 0,0.083,0.25,0.5,1,1.5,2,3,4,5,6,8, and 10h and 0,0.08 3, and 0.167,0.25,0.5,1,2,3,4,5,6,8,10h.All blood samples are centrifugal 10min under 4000rpm, measures blood drug level after treatment.
(4) result of the test is seen Fig. 1, Fig. 2, Fig. 3 and table 4
Table 4: the AUC after rat vein and the trachea administration
ELF/ AUC
Plasma(mean ± S.D.n=3) (P＜0.05)
| TA | i.v. | |
| AUC LEL(μg·h/mL) AUC plasma(μg·h/mL) AUC ELF/AUC plasma | 179.32±20.40 106.44±19.45 1.70±0.12 | 2.28±0.12 108.74±19.15 0.021±0.0026 |
(5) conclusion
Result from table 4 as can be seen, (AUC after the trachea administration
0-t)
ELF/ (AUC
0-t)
Plasma(1.70) ratio and the (AUC behind the intravenously administrable
0-t)
ELF/ (AUC
0-t)
Plasma(0.021) ratio have significance difference (P＜0.05) thereby. can judge that ambroxol hydrochloride dry powder inhalant has targeting.
Claims (5)
1. ambroxol hydrochloride dry powder inhalant is characterized in that: by ambroxol hydrochloride, disperse fluidizer and diluent to form, its percentage by weight is: ambroxol hydrochloride 60%-90%, dispersion fluidizer 10%-30%, diluent 0-40%.
2. ambroxol hydrochloride dry powder inhalant according to claim 1 is characterized in that: the dispersion fluidizer of being addressed is an aminoacid, leucine, isoleucine, one or more in valine or the threonine.
3. ambroxol hydrochloride dry powder inhalant according to claim 1 is characterized in that: the diluent of being addressed is lactose, mannitol, glucose, sucrose or their mixture.
4. the preparation method of an ambroxol hydrochloride dry powder inhalant as claimed in claim 1, it is characterized in that: ambroxol hydrochloride or ambroxol hydrochloride and dispersion fluidizer or ambroxol hydrochloride and dispersion fluidizer and diluent are obtained powder body by spray drying, be collected in gelatin or the plastic capsule or in the bubble-cap of plastic-aluminum or and be included in the multiple dose powder inhaler with depot forms.
5. the preparation method of an ambroxol hydrochloride dry powder inhalant as claimed in claim 1 is characterized in that, comprises the steps:
(1) ambroxol hydrochloride is dissolved in the distilled water with different mixed respectively with diluent or dispersion fluidizer, transfers pH to 6.0 with the sodium hydroxide of 0.1mol/L, behind 0.2 μ m filtering with microporous membrane, standby.
(2) adopt spray drying method that above-mentioned solution is made ambroxol hydrochloride dry powder inhalant, choose satisfactory powder, canned, promptly get preparation of the present invention.
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|---|---|---|---|
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| CN101897720A (en) * | 2010-07-27 | 2010-12-01 | 北京华禧联合科技发展有限公司 | Medicinal composition for treating respiratory disease |
| CN102614123A (en) * | 2011-02-01 | 2012-08-01 | 中国人民解放军军事医学科学院毒物药物研究所 | Ambroxol powder aerosol, its preparation method and application |
| IT201800006909A1 (en) * | 2018-07-04 | 2020-01-04 | DRY POWDER OF AMBROXOL FOR INHALATION USE WITH BRONCHIAL TARGET | |
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| CN113662952A (en) * | 2021-08-25 | 2021-11-19 | 天津中医药大学 | Compound dry powder inhalant and application thereof |
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| CN1323662C (en) * | 2004-06-18 | 2007-07-04 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition containing ambroxol and erdosteine or acetylcysteine and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101897720A (en) * | 2010-07-27 | 2010-12-01 | 北京华禧联合科技发展有限公司 | Medicinal composition for treating respiratory disease |
| CN101897720B (en) * | 2010-07-27 | 2015-09-09 | 北京华禧联合科技发展有限公司 | A kind of pharmaceutical composition for the treatment of respiratory tract disease |
| CN102614123A (en) * | 2011-02-01 | 2012-08-01 | 中国人民解放军军事医学科学院毒物药物研究所 | Ambroxol powder aerosol, its preparation method and application |
| CN102614123B (en) * | 2011-02-01 | 2015-11-25 | 中国人民解放军军事医学科学院毒物药物研究所 | A kind of ambroxol powder spray, Preparation Method And The Use |
| CN110680811A (en) * | 2018-07-04 | 2020-01-14 | 和利康意大利有限公司 | Ambroxol dry powder for inhalation using bronchus as target |
| EP3590502A1 (en) * | 2018-07-04 | 2020-01-08 | Hollycon Italy Pte. Ltd. - S.r.l. | Ambroxol dry powder for inhalation use with bronchial target |
| IT201800006909A1 (en) * | 2018-07-04 | 2020-01-04 | DRY POWDER OF AMBROXOL FOR INHALATION USE WITH BRONCHIAL TARGET | |
| CN111632024A (en) * | 2020-07-02 | 2020-09-08 | 渠静 | Local anesthetic preparation and preparation method and application thereof |
| CN111632024B (en) * | 2020-07-02 | 2021-12-31 | 渠静 | Local anesthetic preparation and preparation method and application thereof |
| CN113662952A (en) * | 2021-08-25 | 2021-11-19 | 天津中医药大学 | Compound dry powder inhalant and application thereof |
| CN113662952B (en) * | 2021-08-25 | 2022-11-22 | 天津中医药大学 | Compound dry powder inhalant for treating idiopathic pulmonary fibrosis and application thereof |
| WO2023024804A1 (en) * | 2021-08-25 | 2023-03-02 | 天津中医药大学 | Compound dry powder inhaler and application thereof |
| CN113925849A (en) * | 2021-10-20 | 2022-01-14 | 宁波易合医药有限公司 | Dry powder inhalation preparation of expectorant and preparation method thereof |
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