CN1301105C - Asthma treating spray - Google Patents

Asthma treating spray Download PDF

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Publication number
CN1301105C
CN1301105C CNB2005100350788A CN200510035078A CN1301105C CN 1301105 C CN1301105 C CN 1301105C CN B2005100350788 A CNB2005100350788 A CN B2005100350788A CN 200510035078 A CN200510035078 A CN 200510035078A CN 1301105 C CN1301105 C CN 1301105C
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asthma
spray
beta
asarone
group
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CN1720906A (en
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方永奇
李翎
石琛
邹衍衍
魏刚
林双峰
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First Affiliated Hospital of Guangzhou University of Chinese Medicine
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First Affiliated Hospital of Guangzhou University of Chinese Medicine
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Abstract

The present invention relates to the field of a spraying agent for treating asthma, particularly to the field of a spraying agent for treating asthma and containing effective plant Chinese medicinal herb components. The spraying agent for treating asthma contains beta-asaricin with a concentration of 5 to 500 g/L, and solvents acceptable on pharmacy. The present invention has the characteristics of less medication dosage, uniform medicine distribution, high medicine absorption speed, high biologic utilization degree, convenient use, etc., avoids the stimulation action to the stomach and intestine, and avoids first pass effect.

Description

Treatment asthma spray
Invention field
The present invention relates to treat the spray field of asthma, particularly the spray field of containing the vegetable Chinese herbal medicine effective ingredient of treatment asthma.
Technical background
When bronchial asthma is sent out, occur coughing, pant, symptoms such as out of breath, uncomfortable in chest, abundant expectoration, heating, cyanosis; Severe patient even can cause death because of respiratory failure, heart failure etc.Doctor trained in Western medicine is mainly used chemical drugs respite such as bronchodilatation medicine and the hormone symptom of stage of attack, but often one meets exopathogenic factor and stimulate and can recur again after the drug withdrawal, may cause degradation series toxic and side effects under the pituitary function and take medicine for a long time.The suction glucocorticoid is to use wherein a kind of method of hormone., neglected the suction glucocorticoid adjustment (Xiong Yaokang of whole body but only paying attention to the treatment of airway inflammation local anti-inflammatory, Yu Bing. the asthma clinical progress. Zhejiang College Of Traditional Chinese Medicine journal .2001,25 (3): 5-7), to wound and child and late developer, glucocorticoid sucked treatment more than 1 year, may cause osteoporosis.Oral hormone treatment can be used as the treatment of keeping of severe asthma, is used for the symptom acute attack, but for minority to the drug-fast patient of hormone, long-term heavy dose of the use does harm rather than good.A little less than the effect of cholinolytic class bronchodilator treatment asthma, and untoward reaction is many.
Chinese medicine asthma is regulated whole body (mainly being immune system) by Chinese medicine, increases the immunocompetence of body, improves the ability that body is resisted affect, reduces the outbreak of asthma even reaches the purpose of long-term remission.Relievining asthma with dispelling pathogenic wind and eliminating phlegm, spasmolytic is method of treatment, numb Zhichuan liquid (Herba Ephedrae, Rhizoma Belamcandae, Pheretima, Semen Armeniacae Amarum, the Rhizoma Pinelliae, Herba Asari, Semen zanthoxyli, Radix Platycodonis, Radix Glycyrrhizae etc.) treatment asthma in acute attack (Liu Xiaohong is penetrated in employing, Liu Qiong, Liang Zhiying, Deng. penetrate the short term effect and the mechanism thereof of numb Zhichuan liquid treatment asthma. Traditional Chinese Medicine University Of Guangzhou's journal, 2000,17 (1): 20).With heavy prescription XIAOQINGLONG TANG (Herba Ephedrae (processed), each 15g of Rhizoma Zingiberis, the Radix Paeoniae Alba, each 30g of Rhizoma Pinelliae Preparatum, Herba Asari, Ramulus Cinnamomi, each 9g of Fructus Schisandrae Chinensis) treatment asthma (FangBing Fu. heavy prescription XIAOQINGLONG TANG treatment asthma 100 examples. Anhui Chinese Medicine College journal, 1999,18 (1): 20).Adopt white mixture (Herba Ephedrae, Semen Ginkgo, Semen Armeniacae Amarum, Fructus Aurantii Immaturus, Flos Magnoliae, Herba Asari, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Scutellariae, Radix Glycyrrhizae etc.) atomization inspiration treatment bronchial asthma in acute attack (the red legend Xiang of fiber crops, Sun Hongwei. the Chinese medicine ultrasonic atomizatio sucks the clinical observation of treatment bronchial asthma. Chinese tcm emergency, 1998,7 (1): 3).The part but present Chinese medicine prevention asthma still has some deficits: 1. medication is a compound preparation, need boil medicine earlier and afterwards take, and boils medicine and uses duration, be inconvenient to carry, drug effect is slow, and is untimely for patient's medication of acute onset, and the patient that need are taken medicine for a long time brings great inconvenience; 2. it is few to play efficient quick-acting pharmaceutical preparation, and medicine only plays the auxiliary treatment effect mostly; 3. the Chinese medicine preparation great majority are oral medication at present, need to produce first pass effect by the gastrointestinal circulation, reduce curative effect of medication, and some has stimulation to gastrointestinal.
The Chinese medicine Rhizoma Acori Graminei of having one's ideas straightened out that eliminates the phlegm all has certain pharmacological action to central nervous system, cardiovascular system, respiratory system, digestive system.The main component of Rhizoma Acori Graminei volatile oil is beta-Asarone (40-80%) and α-asaricin (2-10%), and is at present more to the research of Rhizoma Acori Graminei, and less to the research of beta-Asarone.Studies show that: Rhizoma Acori Graminei can suppress the spontaneous contraction of isolated rabbit intestinal tube, antagonism intestinal tube spasm, strengthen rat at body intestinal tube wriggling and mouse intestinal propulsion functions (Hu Jinguan, Gu Jian, Wang Zhiwang. Rhizoma Acori Graminei and effective ingredient thereof are to the effect of digestive system. Pharmacology and Clinics of Chinese Materia Medica, 1999,15 (2): 16-18.); Have the diastole bronchial smooth muscle effect (Yang Shehua, Wang Zhiwang, Hu Jinguan. Rhizoma Acori Graminei and effective ingredient thereof are to the guinea pig tracheal smooth muscle experimental study of effect. Gansu college of traditional Chinese medicine journal, 2003,20 (2): 12-14.).
Adopt that anapnotherapy treatment bronchial asthma has that dosage is few, drug distribution evenly, drug absorption speed is fast, avoid the gastrointestinal stimulation, avoid first pass effect, bioavailability height, advantage such as easy to use, become the main administering mode of treatment bronchial asthma.
Summary of the invention
The technical issues that need to address of the present invention provide a kind of treatment asthma spray, and meet exopathogenic factor and stimulate and can recur again in order to often to solve after the drug withdrawal that western medical treatment asthma spray exists one, and the shortcoming of taking medicine for a long time and may cause pituitary function to descend.
The mentioned treatment asthma spray of the present invention contains beta-Asarone and the pharmaceutically acceptable solvent of 5~500g/L.
Beta-Asarone can prepare in order to the below method: Rhizoma Acori Graminei adds 8 times of water gagings, by " appendix volatile oil of Chinese pharmacopoeia extracts the Division A League Matches of French Football method, extracts 24 hours, collects volatile oil, volatile oil make with extra care purify beta-Asarone.
The beta-Asarone consumption better is 10~400g/L, preferably 50~200g/L in the treatment asthma spray that the present invention mentions.
Pharmaceutically acceptable solvent of the present invention has wherein one or more mixture of water, ethanol, propylene glycol, ethylene glycol.Preferred solvents is water, ethanol wherein a kind of or mixture, preferably water.
The present invention treats the asthma spray can also contain pharmaceutically acceptable cosolvent.Cosolvent commonly used has wherein one or more mixture of Tween-60, tween 80, hexadecanol, octadecanol, lecithin.It better is wherein a kind of or mixture of Tween-60 and tween 80.Tween 80 preferably.The cosolvent consumption is 5~100g/L, better is 5~50g/L, preferably 5~30g/L.
The present invention treats the asthma spray can also contain wherein one or both mixture of pharmacy acceptable stabilizing agent such as glycerol, Polyethylene Glycol.Can obtain stabilizing agent according to method known to those skilled in the art and preferably use consumption and form.
The present invention treats the asthma spray can also contain pharmacy acceptable antiseptic.Antiseptic commonly used has wherein one or more mixture of sorbic acid, ethanol, benzyl alcohol, nipalgin, phenethyl alcohol, benzalkonium chloride, methyl parahydroxybenzoate.Wherein a kind of or mixture of benzalkonium chloride, methyl parahydroxybenzoate preferably.Can obtain antiseptic according to method known to those skilled in the art and preferably use consumption and form.
The present invention treats the asthma spray can also contain pharmacy acceptable sweeting agent.Sweeting agent commonly used have sucrose, lactose, maltose, glucose, fructose, xylose, stevioside, sorbitol etc. wherein one or both with mixture.Can obtain sweeting agent according to method known to those skilled in the art and preferably use consumption and form.
The present invention treats the asthma spray can also contain pharmacy acceptable aromatic.Aromatic commonly used have Oleum menthae, orange peel oil, aqua cinnamomi, citric acid, flavoring banana essence, flavoring pineapple essence etc. wherein one or more, can obtain aromatic according to method known to those skilled in the art and preferably use consumption and form.
The present invention treats the asthma spray can also contain pharmacy acceptable antioxidant.Antioxidant commonly used has wherein one or more mixture of vitamin C, sodium sulfite, sodium sulfite.Can obtain antioxidant according to method known to those skilled in the art and preferably use consumption and form.
The present invention treats the asthma spray can also contain pharmacy acceptable propellant.Propellant commonly used have isceon, dichlorodifluoromethane, dichlorotetra-fluoroethane, propane, iso-butane, normal butane etc. wherein one or more.Can obtain propellant according to method known to those skilled in the art and preferably use consumption and form.
The present invention treats the asthma spray can also contain osmotic pressure regulator, as sodium chloride, glucose, mannitol, lactose, sorbitol one or more mixture wherein.The preferred sodium chloride of osmotic pressure regulator.Can obtain osmotic pressure regulator according to method known to those skilled in the art and preferably use consumption and form.
The present invention treats asthma spray preparation method and adopts spray preparation method well known by persons skilled in the art.For example beta-Asarone is dissolved in the solvent, adds other pharmaceutically acceptable carrier mix homogeneously then.
The using method that the present invention treats the asthma spray is a using method well known by persons skilled in the art.
The present invention has that dosage is few, drug distribution evenly, drug absorption speed is fast, avoid the gastrointestinal stimulation, avoid first pass effect, bioavailability height, characteristics such as easy to use.
For a better understanding of the present invention, treat asthma spray pharmacological testing and result with the present invention below its purposes in treatment or prevention bronchial asthma, cough-relieving, drug world such as reduce phlegm is described.
The effect experiment method that the present invention treats the asthma spray is as follows.
Get beta-Asarone, add in an amount of pharmaceutically acceptable cosolvent, antiseptic, sweeting agent, aromatic, antioxidant, stabilizing agent, the propellant etc. one or more, it is standby that compound concentration is respectively the treating asthma gas spray of 10g/L, 100g/L, 300g/L, measures the animal drug effect of its treatment asthma.
Its result is as follows:
1) the Cavia porcellus test (spraying causes the method for breathing heavily) of relievining asthma
80 of FMMu Cavia porcelluss, body weight 180~200g, male and female half and half.Animal screening: Cavia porcellus is placed respectively in the aerosol device, sprayed into 1% egg protein 40 seconds with soniclizer, observe drawing of Cavia porcellus and breathe heavily incubation period (promptly beginning time), generally be no more than 150 seconds to asthma attack from spraying, surpass 150 seconds persons and think insensitive, will not select for use.
Formal experiment: 60 of the qualified animals of preliminary election are all divided into groups at random: high dose group, middle dosage group, low dose group, gastric infusion group, positive controls, model control group.Every group 10, each organizes that Cavia porcellus is sprayed respectively or gastric infusion 7 days, every day 2 times.1h after the last administration, each Mus is put into the aerosol device respectively, and the similarity condition during by preliminary election sprayed into 1% egg protein 40 seconds.The record asthma latent time and the latent time of falling.
Table 1 Cavia porcellus test (spraying causes the method for the breathing heavily) result (x ± s) that relievings asthma
Group Size of animal (only) Asthma latent time (s) The latent time (s) of falling
10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group 10g/L beta-Asarone group (gavage) positive controls model control group 10 10 10 10 10 10 57.20±22.45 * 58.90±22.69 ** 59.40±18.97 *** 55.12±12.52 * 58.36±18.72 ** 37.73±9.11 78.40±32.79 * 81.00±50.87 ** 85.30±22.45 *** 75.53±46.36 * 80.09±39.21 ** 45.27±20.59
Annotate: the model control group ratio *P<0.05, *P<0.01, *P<0.001 (down together)
2) the Cavia porcellus test (trachea sheet method) of relievining asthma
50 of FMMu Cavia porcelluss, body weight 450-500g, male and female half and half are shot dead, and trachea is isolated in carefulness immediately, cut whole tracheas from thyroid cartilage down to the trachea crotch, put into Ke-Heng Shi liquid, at the outside of belly (cartilage anchor ring) longitudinal incision of trachea, again every 3 cartilaginous ring crosscuts, the longitudinal incision place of every section trachea sheet strings mutually with on the linear slit.
The trachea sheet specimen of sewing it up is put into the isolated organ bath that fills Ke-Heng Shi liquid, and glass ventilation hook is fixed in the lower end, and the upper end is connected to (about 1g loads) on the tension transducer with long line, so that the record reaction.Temperature constant is 37 ℃ in the bath, and lasting oxygen supply.Specimen balance 30 minutes, administration whenever added medicine contact 15 minutes, observed drug reaction, changed liquid then, treat that baseline recovers after, give another medicine.Dosing step is: (1). histamine phosphate 0.5 μ g/ml (concentration in the bath, down together), observation has or not contractile response, determines the function status of specimen.Normal as the specimen function, record reaction tension force.(2). after the method for cumulative scale dosing, observe being subjected to of the relexation of reagent thing to tracheal smooth muscle.(3). change liquid.(4) replace histamine phosphate with acecoline (0.5 μ g/ml), repeat (1) to (3) step.
Table 2 Cavia porcellus relieving asthma test (trachea sheet method) result (x ± s, g)
Group Size of animal (only) Histamine Acetylcholine
Administration backward pull reduction value Administration backward pull reduction value
10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls model control group 10 10 10 10 10 1.62±0.21 *** 1.88±0.56 *** 1.94±0.42 *** 1.54±0.36 *** 0.16±0.19 1.28±0.68 *** 1.85±0.52 *** 1.91±0.34 *** 0.99±0.46 *** 0.035±0.065
3) mice cough-relieving test (sulfur dioxide stimulus method)
NIH mice male and female half and half, body weight 18-22g, all groupings at random: high dose group, middle dosage group, low dose group, positive controls, model control group.Every group 10, each organizes mice difference spray delivery 7 days, every day 2 times.After the last administration 1 hour, mice is put into the wide mouthed bottle of 500ml, feed sulfur dioxide gas 10ml, observe and write down the incubation period (to begin to the required time of cough takes place be incubation period by feeding sulfur dioxide) of each mouse cough.
The sulfur dioxide gas preparation: with 250ml side mouth flask, the side mouth connects bladders with rubber tube, contains sodium sulfite in the side mouth flask, adorn a burette on the flask bottle stopper, in put concentrated sulphuric acid, open the piston on the burette, after concentrated sulphuric acid drips, in bottle, produce sulfur dioxide gas, gas is stored in the bladders, clamps with mosquito forceps, during application, draw 10ml with syringe, inject in the 500ml wide mouthed bottle.
Table 3 mice cough-relieving test (sulfur dioxide stimulus method) result (x ± s)
Group Size of animal (only) Cough latent period (second) Cough number of times (inferior)
10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls model control group 10 10 10 10 10 25.00±4.63 *** 28.86±3.32 *** 29.38±4.66 *** 26.50±9.89 ** 13.20±5.02 26.23±11.35 *** 22.57±12.21 *** 20.25±19.36 ** 29.00±16.27 ** 49.90±7.25
4) the mice test (the phenol red method of trachea section) of reducing phlegm
50 of NIH mices, male and female half and half, body weight 18-22g, grouping and administration are the same.After the last administration 30 minutes, mouse peritoneal is injected 5% phenol red (500mg/kgbw), put to death animal after half an hour, peel off the trachea surrounding tissue, cut one section trachea down to the trachea bifurcation, put into the test tube that fills the 2ml normal saline from thyroid cartilage, add 2 1mol/L sodium hydroxide again, use spectrophotometer, under wavelength 546nm, survey the OD value, calculate phenol red output with phenol red standard curve.
Table 4 mice test (the phenol red method of the trachea section) result (x ± s) that reduces phlegm
Group Size of animal (only) Phenol red output (μ g/ml)
10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L β one asaricin group positive controls model control group 10 10 10 10 10 1.56±0.20 *** 1.69±0.35 *** 1.81±0.32 *** 1.21±0.13 *** 0.56±0.11
5) mouse corrosion disease test (ear swelling)
50 of NIH mices, male, body weight 18-22g, grouping and administration are the same.1h after the last administration, ear two sides, every Mus left side is coated with 100% dimethylbenzene proinflammatory agent, 25 μ l and causes inflammation, and auris dextra compares.Put to death animal after causing scorching 1h, cut two ears along the auricle baseline, lay the same position of ears disk with diameter 9mm card punch, electronic analytical balance is weighed, and calculates the swelling degree.Swelling degree=left auricle weight-auris dextra sheet is heavy.
The result of table 5 mouse corrosion disease test (ear swelling) (x ± s)
Group Size of animal (only) Swelling degree (mg)
10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls model control group 10 10 10 10 10 5.21±5.13 * 6.31±6.52 * 5.65±6.35 * 4.65±3.86 ** 11.08±5.12
6) rat antiinflammatory test (granuloma)
50 of SD rats, male, body weight 180-200g, it is the same to divide into groups.Intraperitoneal injection of anesthesia (chloral hydrate 300g/kg), strange portion about every Mus, routine disinfection, respectively cut the long osculum of 1cm, with of autoclaving cotton balls (penicillin and streptomycin mixed liquor 0.2ml, the immersion of ophthalmology tweezer with 20mg, oven dry) implantation is subcutaneous outside otch, immediately skin suture.From operation same day, each organizes administration every day 2 times, and successive administration 7 days was opened former otch on the 8th day, and cotton balls is taken out together with connective tissue on every side, rejects fatty tissue, puts 70 ℃ of oven dry 24h in the baking oven, weighs.With claim weight deduct the former weight of cotton balls and promptly get granuloma weight, respectively organize granuloma weight.
Table 6 rat antiinflammatory test (granuloma) result (x ± s)
Group Size of animal (only) Granuloma heavy (mg/100gbw)
10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls model control group 10 10 10 10 10 18.11±3.75 ** 17.25±6.23 ** 15.92±8.16 *** 16.10±6.54 *** 25.16±3.98
7) influence of mouse immune organ thymus, spleen is tested
50 of NIH mices, male, body weight 18-22g, it is the same to divide into groups.Every day, spray delivery was 2 times, and successive administration 7 days behind the last administration 1h, is plucked eyeball sacrificed by exsanguination animal, weighs, and won thymus, spleen is weighed, and respectively organizes the body of gland index.Be the body of gland index with thymus and spleen weight (mg) with likening to of body weight (g).
The result of table 7 mouse immune organ thymus, spleen test (x ± s)
Group Size of animal (only) Thymus index (mg/10gbw) Spleen index (mg/10gbw)
10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls model control group 10 10 10 10 10 5.83±1.52 ** 5.76±1.05 ** 5.52±1.15 ** 5.35±1.13 ** 3.04±0.98 7.14±1.25 * 6.25±2.43 * 6.38±2.21 * 6.06±2.32 * 4.11±1.62
8) mice reticuloendothelial system carbon granule clearance test
50 of NIH mices, body weight 18-22g, male, grouping and administration are the same.Last administration 1h injects the Chinese prepared Chinese ink of dilution (with 4 times of 1% gelatin solution dilutions) 0.1ml/10gbw in caudal vein, and 30 seconds and 6 minutes are got blood 0.025ml with the special blood suction pipe of getting from the mouse orbit rear vein beard behind injection prepared Chinese ink, are blown into 0.1%Na at once 2CO 3Among the solution 2ml, suction pipe sucks, blows out several and fully washes out the blood that the suction pipe wall adheres in this liquid, be dissolved in 2ml0.1%Na with 0.025ml normal mouse blood 2CO 3The solution lieutenant colonel zero, in spectrophotometer 675nm place colorimetric, calculates phagocytic index K and engulfs factor alpha (correction phagocytic index).
K=(IogOD 1-IogOD 2)/(t 2-t 1) α=W*K 1/3/WLS
Annotate: OD 1, OD 2Be the optical density of different time institute blood sampling, t 2-t 1, being the time difference of blood sampling, W is a body weight, WLS closes heavily for the liver spleen.
The result of table 8 mice reticuloendothelial system carbon granule clearance test (x ± s)
Group Size of animal (only) Phagocytic index K Engulf factor alpha
10g/L beta-Asarone group 100g/L beta-Asarone group 300g/L beta-Asarone group positive controls model control group 10 10 10 10 10 0.0536±0.0425 * 0.0538±0.0321 * 0.0429±0.0392 ** 0.0402±0.0316 ** 0.0906±0.0453 4.36±1.33 * 4.93±1.61 * 5.85±1.02 * 5.26±1.75 * 3.12±1.63
Show that from above-mentioned experiment treatment asthma spray can prolong its asthma attack incubation period, the incubation period of falling, alleviate attack degree asthmatic guinea pigs, and the spray delivery group is longer than gastric infusion group asthma attack incubation period, the incubation period of falling; Can be obviously to antihistamine and acetylcholine, the bronchial smooth muscle of the stripped Cavia porcellus of diastole; The mouse cough that sulfur dioxide is caused has the obvious suppression effect; Make the juice output increase of mice trachea section; Have relieving asthma, antitussive action; Mice ear inflammation and rat granuloma there are inhibitory action, have the weight that antiinflammatory action can increase the immune organ of mice, strengthen mice reticuloendothelial system carbon granule and clean up ability, the effect that strengthens mouse immune power is arranged.
The specific embodiment
Below be specific embodiments of the invention, but be not limited to described embodiment.
Embodiment 1
Get the 10g beta-Asarone, add 10ml glycerol, 200ml ethanol, the 1g stevioside adds water to 1000ml, behind the mix homogeneously, seals in the medicine bottle of packing into, sterilizes into product.
Embodiment 2
Get 100g beta-Asarone, 100g Tween-60,1g Oleum menthae, heating for dissolving adds water to 1000ml after the cooling in the 500ml propylene glycol, behind the mix homogeneously, seals in the medicine bottle of packing into, sterilizes into product.
Embodiment 3
Get the 200g beta-Asarone, add the 50g tween 80,200ml glycerol, the 2g octadecanol, the 2g flavoring banana essence adds water to 1000ml, behind the mix homogeneously, is pressed into every bottle of about 5.5g of dichlorodifluoromethane with pressure filling, makes product.
Embodiment 4
Get the 300g beta-Asarone, 100ml glycerol, in the 300ml ethanol, the 1g orange peel oil adds water to 1000ml, behind the mix homogeneously, seals in the medicine bottle of packing into, sterilizes into product.
Embodiment 5
Get beta-Asarone 500g, propylene glycol 100ml, 300ml in the ethanol, flavoring pineapple essence 1g adds water and causes 1000ml, behind the mix homogeneously, is pressed into every bottle of about 6g of isceon with pressure filling, makes product.
Embodiment 6
Get beta-Asarone 400g and be dissolved in propylene glycol 500ml, add water to 1000ml, behind the mix homogeneously, become product in the spray container of packing into after the sterilization.
Embodiment 7
Get beta-Asarone 250g and be dissolved in ethanol 250ml, add water to 1000ml, behind the mix homogeneously, the sterilization back is pressed into every bottle of about 5g of propane with pressure filling, makes product.
Embodiment 8
Get beta-Asarone 150g and be dissolved in ethylene glycol 150ml, add water to 1000ml, behind the mix homogeneously, the sterilization back is pressed into iso-butane and every bottle of about 6g of normal butane with pressure filling, makes product.
Embodiment 9
Get beta-Asarone 80g and be dissolved in propylene glycol 100ml and ethanol 100ml, add water to 1000ml, behind the mix homogeneously, become product in the spray container of packing into after the sterilization.
Embodiment 10
Get the 10g beta-Asarone, the 2g Tween-60, the 3g tween 80 adds water to 1000ml, behind the mix homogeneously, becomes product in the spray container of packing into after the sterilization.
Embodiment 11
Get the 50g beta-Asarone, the 10g tween 80 is dissolved in propylene glycol 100ml and ethanol 100ml, adds water to 1000ml, behind the mix homogeneously, becomes product in the spray container of packing into after the sterilization.
Embodiment 12
Get the 80g beta-Asarone, the 10g tween 80, the 10ml hexadecanol, the 35ml Polyethylene Glycol adds water to 1000ml, behind the mix homogeneously, becomes product in the spray container of packing into after the sterilization.
Embodiment 13
Get beta-Asarone 200g and tween 80 50g and be dissolved in the 1000ml water, behind the mix homogeneously, sterilization back is pressed into propane and iso-butane, every bottle of about 6g of normal butane with pressure filling, makes product.
Embodiment 14
Get beta-Asarone 400g, tween 80 100g, Tween-60 200g, water is settled to 1000ml, behind the mix homogeneously, becomes product in the spray container of packing into after the sterilization.
Embodiment 15
Get beta-Asarone 300g, tween 80 50g, Tween-60 20g, hexadecanol 20g, water is settled to 1000ml, behind the mix homogeneously, becomes product in the spray container of packing into after the sterilization.
Embodiment 16
Get beta-Asarone 200g, tween 80 20g, lecithin 10g, water is settled to 1000ml, behind the mix homogeneously, becomes product in the spray container of packing into after the sterilization.
Embodiment 17
Get beta-Asarone 180g, tween 80 40g, add and be dissolved in glycerol 200ml, the cooling back adds sodium chloride 9g, sodium sulfite 0.2g, sucrose 1g, benzalkonium chloride 2.5g, phosphate buffer solution with ph5.5 is settled to 1000ml, behind the mix homogeneously, become product in the spray container of packing into after the sterilization.
Embodiment 18
Get beta-Asarone 150g, tween 80 20g, add and be dissolved in glycerol 150ml, the cooling back adds sodium chloride 7g, 0.2g vitamin C, sucrose 1.2g, methyl parahydroxybenzoate 1.5g, phosphate buffer solution with ph5.5 is settled to 1000ml, behind the mix homogeneously, become product in the spray container of packing into after the sterilization.
Embodiment 19
Get beta-Asarone 100g, flavoring pineapple essence 1g, tween 80 20g, heating for dissolving is at propylene glycol 100ml, and 100ml in the ethanol adds sodium chloride 7g, sodium sulfite 0.2g, glucose 2g, benzalkonium chloride 2.5g after the cooling, behind the mix homogeneously, be settled to 1000ml with the tartaric acid of ph5.5 and the buffer solution of salt thereof, the sterilization back is pressed into every bottle of about 6g of dichlorodifluoromethane with pressure filling, makes product.
Embodiment 20
Get beta-Asarone 100g, flavoring pineapple essence 1g, tween 80 20g, glycerol 20ml, Polyethylene Glycol 30ml, heating for dissolving is at ethylene glycol 100ml, 100ml in the ethanol, the cooling back adds sodium chloride 5g, sodium sulfite 0.3g, glucose 2g, benzalkonium chloride 1g, methyl parahydroxybenzoate 1g behind the mix homogeneously, is settled to 1000ml with the tartaric acid of ph5.5 and the buffer solution of salt thereof, the sterilization back is pressed into every bottle of about 8g of dichlorodifluoromethane with pressure filling, makes product.

Claims (10)

1. treat the asthma spray for one kind, it is characterized in that containing beta-Asarone and the pharmaceutically acceptable solvent of 5~500g/L.
2. the described treatment asthma of claim 1 spray is characterized in that the beta-Asarone consumption is 10~400g/L.
3. the described treatment asthma of claim 1 spray is characterized in that the beta-Asarone consumption is 50~200g/L.
4. the described treatment asthma of claim 1 spray, wherein solvent is wherein one or more mixture of water, ethanol, propylene glycol, ethylene glycol.
5. the described treatment asthma of claim 1 spray, wherein solvent is a water.
6. one of them described treatment asthma spray of claim 1 to 5, it is characterized in that containing cosolvent, consumption is 5~100g/L, and wherein cosolvent is wherein one or more mixture of Tween-60, tween 80, hexadecanol, octadecanol, lecithin.
7. the described treating asthma spray of claim 6, wherein cosolvent is wherein a kind of or the two a mixture of Tween-60, tween 80.
8. the described treating asthma spray of claim 6 is characterized in that the cosolvent consumption is 5~50g/L.
9. the described treating asthma spray of claim 6 is characterized in that the cosolvent consumption is 5~30g/L.
10. the described treating asthma spray of claim 1, it is characterized in that containing pharmaceutically acceptable stabilizing agent, sweeting agent, antiseptic, aromatic, osmotic pressure regulator, antioxidant, propellant wherein one or more.
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CN1579448A (en) * 2003-08-08 2005-02-16 浙江工业大学 Nasal spray for treating headache and hemicrania and its preparation method

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