CN112043687A - Inhalation powder inhalation for treating asthma and preparation method thereof - Google Patents
Inhalation powder inhalation for treating asthma and preparation method thereof Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The invention discloses an inhalation aerosol powder for treating asthma, which consists of carrier micro powder, drug-loaded micro powder of formoterol and andrographolide micro powder, wherein the delivery amount of the drug-loaded micro powder of formoterol is 1-20 mu g, and the particle size of at least 99% (w/w) of the drug-loaded micro powder is less than 10 mu m; the delivery amount of the andrographolide micropowder is 20-1000 mu g, and the particle size of at least 99% (w/w) of the andrographolide micropowder is less than 10 mu m; the carrier micropowder is selected from one or more of physiologically acceptable sugar, polyalcohol, and amino acid, and has particle diameter of at least 10% (w/w) of microparticles less than 10 μm. The inhalation powder cloud agent can effectively relieve asthma symptoms and has better anti-inflammatory effect and bronchiectasis effect; the preparation method is simple to operate, the cost is reduced, and the problem of great difference between the dosage of the main drug and the auxiliary material is solved.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to an inhalation aerosol powder for treating asthma and a preparation method thereof.
Background
Asthma is one of chronic diseases common in the world, and at present, the types of medicines for treating asthma are as follows: 1. an adrenoreceptor agonist; 2. anti-allergic drugs; 3. theophylline class of drugs; 4. a glucocorticoid. Formoterol (Fomoterol) is a beta 2-adrenoceptor agonist successfully developed in the later 80 s, has strong action and long retention time, is widely applied to asthma and other respiratory obstruction diseases, and currently, the fumarate salt of the formoterol is mainly applied. The racemate formoterol has two asymmetric carbon atoms in its structure, so has four different stereoconfigurations, i.e., (R, R) -form, (S, S) -form (enantiomer), (R, S) -form, (S, R) -form (diastereomer). Currently, the most widely used clinical application is an equal mixture of the (R, R) and (S, S) forms of formoterol, whereas the (S, S) -isomer is almost inactive compared to the (R, R) -isomer. Therefore, by using the active isomer (R, R) -formoterol, the dosage of the drug can be reduced, thereby reducing the incidence of toxic and side effects.
An inhalation powder inhalation (aerosol of micropowders for inhalation) is a delivery system that is mainly used for active inhalation of an aerosolized drug into the lungs from a patient using a specially designed dry powder inhalation device in the form of a capsule, vesicle or multi-dose reservoir with micronized drug or a carrier to exert systemic or local action. The powder inhalation is effective for inhalation or spray administration of low and high dose drugs. Compared with aerosol, the powder aerosol has the biggest advantages that when the powder aerosol is used, airflow of a patient is the only power for the powder to enter the body, so that the powder aerosol has no coordination difficulty, the occurrence rate of side effects of the medicine is reduced, and the powder aerosol is particularly suitable for old people and children.
The conventional preparation method of the powder inhalation comprises the following steps: (1) mechanically grinding the drug to 10 μm; (2) sieving the carrier with a 100-mesh sieve to obtain the carrier with the particle size of about 150 mu m; (3) mixing the pulverized medicine with the carrier. In the (R, R) -formoterol powder aerosol, the dosage of the (R, R) -formoterol is very small, is only microgram and is greatly different from the dosage of auxiliary materials; the powder inhalation prepared by the conventional method has strong hygroscopicity and poor fluidity; and because the (R, R) -formoterol is expensive, the conventional method for preparing the inhalation aerosol powder has large medicament loss and high cost, so that the ideal (R, R) -formoterol inhalation aerosol powder is difficult to obtain in the actual preparation process.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide the powder inhalation for treating asthma and the preparation method thereof, and the powder inhalation can effectively relieve asthma symptoms and has better anti-inflammatory effect and bronchodilation effect; the preparation method is simple to operate, the cost is reduced, and the problem of great difference between the dosage of the main drug and the auxiliary material is solved.
In order to solve the problems, the technical scheme adopted by the invention is as follows:
an inhalation aerosol powder for treating asthma, which consists of carrier micro powder, formoterol drug-loaded micro powder and andrographolide micro powder, wherein the delivery amount of the formoterol drug-loaded micro powder is 1-20 mu g, and the particle size of at least 99% (w/w) of the formoterol drug-loaded micro powder is less than 10 mu m; the delivery amount of the andrographolide micropowder is 20-1000 mu g, and the particle size of at least 99% (w/w) of the andrographolide micropowder is less than 10 mu m; the carrier micropowder is selected from one or more of physiologically acceptable sugar, polyalcohol, and amino acid, and has particle diameter of at least 10% (w/w) of microparticles less than 10 μm.
In the carrier micro powder, physiologically acceptable sugar is selected from one or more of lactose, sucrose, glucose, fructose, maltose and trehalose; the polyalcohol is selected from one or more of mannitol, xylitol and sorbitol; the amino acid is selected from one or more of leucine, alanine, valine, isoleucine, glycine, phenylalanine, proline, tryptophan, serine, tyrosine, cysteine, methionine, glutamic acid, threonine, aspartic acid, glutamine, lysine, arginine, histidine and asparagine.
As a preferred embodiment of the invention, the carrier micro powder is selected from one or more of lactose, mannitol or xylitol.
In a preferred embodiment of the present invention, the fine carrier powder is lactose.
As a preferred embodiment of the invention, the formoterol drug carrying micro powder has a particle size of at least 70% (w/w) in the range of 0.5-7 μm.
In a preferable embodiment of the invention, in the formoterol drug-loaded micro powder, formoterol accounts for 0.1-10% (w/w), and a water-soluble carrier accounts for 90-99.9% (w/w); the water soluble carrier is one or more of physiologically acceptable sugar, polyalcohol or amino acid.
In a preferred embodiment of the invention, the formoterol drug-loaded micro powder comprises 0.2-2% (w/w) of formoterol and 99.8-98% (w/w) of water-soluble carrier; the water soluble carrier is one or more of lactose, mannitol or leucine.
The invention also provides a preparation method of the inhalation aerosol powder for treating asthma, which comprises the following steps:
1) the preparation of the carrier micro powder comprises the following steps:
(1) one or more of physiologically acceptable sugar, polyalcohol and amino acid is prepared into 0.1g/100ml to saturated aqueous solution,
(2) the solution is atomized into fine droplets,
(3) spraying the mixture into an organic solvent to form a mixture,
(4) drying;
2) the preparation of the medicine carrying micro powder comprises the following steps:
(1) formoterol and a water-soluble carrier are dissolved in water, the solute content in the solution is 1-10g/100ml,
(2) spray drying the solution;
3) the preparation of the andrographolide micropowder comprises the following steps:
(1) dissolving andrographolide micropowder and water soluble carrier in water to obtain solution with solute content of 1-10g/100ml,
(2) spray drying the solution;
4) mixing the carrier micropowder, the medicine carrying micropowder and the andrographolide micropowder by equivalent gradual addition method to obtain the preparation.
As a preferred embodiment of the present invention, in step 2) (1), the solute content in the solution is 2 to 7g/100 ml.
As a preferred embodiment of the present invention, the organic solvent in step 1) (3) is one or more selected from ethanol, isopropanol, acetone, n-butanol, sec-butanol, ethyl acetate, butyl acetate, tert-butyl methyl ether, ethyl formate, n-heptane, isobutyl acetate, isopropyl acetate, methyl acetate, butanone, methyl isobutyl ketone, isobutanol, n-pentane, n-pentanol, n-propanol, and petroleum ether.
Compared with the prior art, the invention has the beneficial effects that:
the inhalation powder cloud agent can effectively relieve asthma symptoms and has better anti-inflammatory effect and bronchiectasis effect; the preparation method is simple to operate, the cost is reduced, and the problem of content uniformity caused by great difference of the dosages of the main drug and the auxiliary materials is solved. The whole preparation method is simple to operate, low in cost and easy to realize industrialization.
Detailed Description
An inhalation aerosol powder for treating asthma, which consists of carrier micro powder, formoterol drug-loaded micro powder and andrographolide micro powder, wherein the delivery amount of the formoterol drug-loaded micro powder is 1-20 mu g, and the particle size of at least 99% (w/w) of the formoterol drug-loaded micro powder is less than 10 mu m; the delivery amount of the andrographolide micropowder is 20-1000 mu g, and the particle size of at least 99% (w/w) of the andrographolide micropowder is less than 10 mu m; the carrier micropowder is selected from one or more of physiologically acceptable sugar, polyalcohol, and amino acid, and has particle diameter of at least 10% (w/w) of microparticles less than 10 μm.
In the formula, the physiologically acceptable sugar in the carrier micro powder is selected from one or more of lactose, sucrose, glucose, fructose, maltose and trehalose; the polyalcohol is selected from one or more of mannitol, xylitol and sorbitol; the amino acid is selected from one or more of leucine, alanine, valine, isoleucine, glycine, phenylalanine, proline, tryptophan, serine, tyrosine, cysteine, methionine, glutamic acid, threonine, aspartic acid, glutamine, lysine, arginine, histidine and asparagine. Preferably, the formoterol drug loaded micropowder has a particle size of at least 70% (w/w) in the range of 0.5-7 μm. Preferably, in the formoterol drug-loaded micro powder, the formoterol accounts for 0.1-10% (w/w), and the water-soluble carrier accounts for 90-99.9% (w/w); the water soluble carrier is one or more of physiologically acceptable sugar, polyalcohol or amino acid. Further preferably, formoterol is present in an amount of 0.2% to 2% (w/w), the water-soluble carrier is present in an amount of 99.8% to 98% (w/w); the water soluble carrier is one or more of lactose, mannitol or leucine.
The preparation method of the inhalation aerosol powder for treating asthma comprises the following steps:
1) the preparation of the carrier micro powder comprises the following steps:
(1) one or more of physiologically acceptable sugar, polyalcohol and amino acid is prepared into 0.1g/100ml to saturated aqueous solution,
(2) the solution is atomized into fine droplets,
(3) spraying the mixture into an organic solvent to form a mixture,
(4) drying;
2) the preparation of the medicine carrying micro powder comprises the following steps:
(1) formoterol and a water-soluble carrier are dissolved in water, the solute content in the solution is 1-10g/100ml,
(2) spray drying the solution;
3) the preparation of the andrographolide micropowder comprises the following steps:
(1) dissolving andrographolide micropowder and water soluble carrier in water to obtain solution with solute content of 1-10g/100ml,
(2) spray drying the solution;
4) mixing the carrier micropowder, the medicine carrying micropowder and the andrographolide micropowder by equivalent gradual addition method to obtain the preparation.
As a preferred embodiment of the present invention, in step 2) (1), the solute content in the solution is 2 to 7g/100 ml.
In the above steps, the organic solvent is selected from one or more of ethanol, isopropanol, acetone, n-butanol, sec-butanol, ethyl acetate, butyl acetate, tert-butyl methyl ether, ethyl formate, n-heptane, isobutyl acetate, isopropyl acetate, methyl acetate, butanone, methyl isobutyl ketone, isobutanol, n-pentane, n-pentanol, n-propanol, and petroleum ether.
EXAMPLE 1 preparation of Fine Carrier powder
0.5g of lactose was weighed and dissolved in 500ml of deionized water. The solution was sprayed with a spray dryer, and the droplets were sprayed into isopropyl alcohol, with stirring, all the time. And after spraying is finished, filtering, drying and crushing a filter cake to obtain the nano-composite material. When spraying is carried out, the speed of atomizing airflow is controlled to be 30ml/h, and the speed of a peristaltic pump is controlled to be 8 ml/min.
Inspection results of the powder: the particle size of the carrier micro powder is 80 percent, the particle size is in the range of 40-100 mu m, and the angle of repose is 35.6 degrees.
EXAMPLE 2 preparation of Fine Carrier powder
50g of lactose was weighed and added with water to prepare a saturated solution. The solution was sprayed with a spray dryer, and the droplets were sprayed into isopropyl alcohol, with stirring, all the time. And after spraying is finished, filtering, drying and crushing a filter cake to obtain the nano-composite material. When spraying is carried out, the speed of atomizing airflow is controlled to be 30ml/h, and the speed of a peristaltic pump is controlled to be 1 ml/min.
Inspection results of the powder: the particle size of the carrier micro powder is 80 percent, the particle size is in the range of 40-100 mu m, and the angle of repose is 36.7 degrees.
EXAMPLE 3 preparation of Fine Carrier powder
50g of mannitol were weighed and dissolved in 150ml of deionized water. The solution was sprayed with a spray dryer, and the droplets were sprayed into anhydrous ethanol, and stirred at all times. And after spraying is finished, filtering, drying and crushing a filter cake to obtain the nano-composite material. When spraying is carried out, the speed of atomizing airflow is controlled to be 30ml/h, and the speed of a peristaltic pump is controlled to be 3 ml/min.
Inspection results of the powder: the particle size of the carrier micro powder is 80 percent, the particle size is in the range of 40-100 mu m, and the angle of repose is 36.4 degrees.
EXAMPLE 4 preparation of Fine Carrier powder
50g of xylitol was weighed and dissolved in 200ml of deionized water. The solution was sprayed with a spray dryer, and the droplets were sprayed into anhydrous ethanol, and stirred at all times. And after spraying is finished, filtering, drying and crushing a filter cake to obtain the nano-composite material. When spraying is carried out, the speed of atomizing airflow is controlled to be 30ml/h, and the speed of a peristaltic pump is controlled to be 4 ml/min.
Inspection results of the powder: the particle size of the carrier micro powder is 80%, the particle size is in the range of 40-100 μm, and the angle of repose is 37.5 degrees.
Example 5 preparation of formoterol drug loaded micropowder
The components are weighed according to 0.01g of formoterol and 5g of lactose and dissolved in 500ml of deionized water. And carrying out spray drying on the solution by using a spray dryer to obtain the formoterol drug-loaded micro powder. When the spray drying is carried out, the air inlet temperature is controlled to be 110 ℃, the air outlet temperature is controlled to be 60 ℃, the atomizing airflow speed is controlled to be 30ml/h, and the peristaltic pump speed is controlled to be 3 ml/min.
Inspection results of the powder: the particle size of the formoterol drug-loaded micro powder is that the particle size of 80% of particles is in the range of 0.5-5 μm, and the particle size of 90% of particles is less than 10 μm; the angle of repose was 43.4 degrees.
Example 6 preparation of formoterol drug loaded micropowder
The components are weighed according to 0.05g of formoterol and 25g of lactose and dissolved in 250ml of deionized water. And (R, R) -formoterol medicine carrying micro powder is obtained by carrying out spray drying on the solution by a spray dryer. When the spray drying is carried out, the air inlet temperature is controlled to be 110 ℃, the air outlet temperature is controlled to be 60 ℃, the atomizing airflow speed is controlled to be 30ml/h, and the peristaltic pump speed is controlled to be 5 ml/min.
Inspection results of the powder: the particle size of the formoterol drug-loaded micro powder is that the particle size of 80% of particles is in the range of 0.5-5 μm, and the particle size of 90% of particles is less than 10 μm; the angle of repose was 41.8 degrees.
Example 7 preparation of formoterol drug loaded micropowder
The components were weighed out in amounts of formoterol 0.022g and lactose 11g and dissolved in 250ml of deionized water. And (R, R) -formoterol medicine carrying micro powder is obtained by carrying out spray drying on the solution by a spray dryer. When the spray drying is carried out, the air inlet temperature is controlled to be 110 ℃, the air outlet temperature is controlled to be 60 ℃, the atomizing airflow speed is controlled to be 30ml/h, and the peristaltic pump speed is controlled to be 4 ml/min.
Inspection results of the powder: the particle size of the formoterol drug-loaded micro powder is that the particle size of 80% of particles is in the range of 0.5-5 μm, and the particle size of 90% of particles is less than 10 μm; the angle of repose was 42.6 degrees.
EXAMPLE 8 preparation of formoterol drug loaded micropowder
The components are weighed according to 0.022g of formoterol and 11g of mannitol and dissolved in 250ml of deionized water. And (R, R) -formoterol medicine carrying micro powder is obtained by carrying out spray drying on the solution by a spray dryer. When the spray drying is carried out, the air inlet temperature is controlled to be 110 ℃, the air outlet temperature is controlled to be 60 ℃, the atomizing airflow speed is controlled to be 30ml/h, and the peristaltic pump speed is controlled to be 2 ml/min.
Inspection results of the powder: the particle size of the formoterol drug-loaded micro powder is within the range of 0.5-5 mu m, and the particle size of 90% of particles is less than 10 mu m; the angle of repose was 41.2 degrees.
Example 9 preparation of fine powder of andrographolide
Weighing each component according to 0.44g of andrographolide extract and 11g of leucine, dissolving in 250ml of deionized water, performing spray drying on the solution by using a spray dryer to obtain andrographolide drug-loaded micropowder, and controlling the air inlet temperature to be 110 ℃, the air outlet temperature to be 60 ℃, the atomizing airflow speed to be 30ml/h and the peristaltic pump speed to be 4ml/min during spray drying.
Inspection results of the powder: the particle size of the andrographolide micropowder is that the particle size of 80% of particles is in the range of 0.5-5 μm, and the particle size of 90% of particles is less than 10 μm; the angle of repose was 40.2 degrees.
EXAMPLE 10 inhalation powder Aerosol preparation
Formoterol medicine carrying micro powder (containing formoterol 0.022g) 11.4g
Andrographolide micropowder (containing herba Andrographitis 0.44g) 44.8g
14g of carrier micro powder (the particle size is between 40 and 140 mu m)
Sieving the carrier micropowder with a particle size of 40-140 μm with a 100 mesh sieve, mixing with andrographolide micropowder and drug-loaded micropowder by equivalent incremental method, and filling into No. 4 hollow capsule with a filling amount of 30mg per capsule.
According to the determination method of Chinese pharmacopoeia 2005 edition, the detection shows that the emptying rate of the capsule is 99.1%, the fog drop (particle) distribution of the capsule is 17.2%, and other indexes all meet the requirements of inhalation of powder aerosol in Chinese pharmacopoeia 2005 edition.
The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.
Claims (10)
1. An inhalation powder inhalation for treating asthma, which is characterized in that: the drug-loaded formoterol liposome consists of carrier micro-powder, drug-loaded formoterol micro-powder and andrographolide micro-powder, wherein the delivery amount of the drug-loaded formoterol micro-powder is 1-20 mu g, and the particle size of at least 99% (w/w) of the drug-loaded formoterol micro-powder is less than 10 mu m; the delivery amount of the andrographolide micropowder is 20-1000 mu g, and the particle size of at least 99% (w/w) of the andrographolide micropowder is less than 10 mu m; the carrier micropowder is selected from one or more of physiologically acceptable sugar, polyalcohol, and amino acid, and has particle diameter of at least 10% (w/w) of microparticles less than 10 μm.
2. The dry aerosol inhaler for treating asthma according to claim 1, wherein: in the carrier micro powder, the physiologically acceptable sugar is selected from one or more of lactose, sucrose, glucose, fructose, maltose and trehalose; the polyalcohol is selected from one or more of mannitol, xylitol and sorbitol; the amino acid is selected from one or more of leucine, alanine, valine, isoleucine, glycine, phenylalanine, proline, tryptophan, serine, tyrosine, cysteine, methionine, glutamic acid, threonine, aspartic acid, glutamine, lysine, arginine, histidine and asparagine.
3. The dry aerosol inhaler for treating asthma according to claim 2, wherein: the carrier micro powder is selected from one or more of lactose, mannitol or xylitol.
4. The dry aerosol inhaler for treating asthma according to claim 3, wherein: the carrier micro powder is lactose.
5. The dry aerosol inhaler for treating asthma according to claim 1, wherein: the particle size of the formoterol drug-loaded micro-powder is at least 70% (w/w) within the range of 0.5-7 μm.
6. The dry aerosol inhaler for treating asthma according to claim 1, wherein: in the formoterol drug-loaded micro powder, the formoterol accounts for 0.1-10% (w/w), and the water-soluble carrier accounts for 90-99.9% (w/w); the water soluble carrier is one or more of physiologically acceptable sugar, polyalcohol or amino acid.
7. The dry aerosol inhaler for treating asthma according to claim 6, wherein: in the formoterol drug-loaded micro powder, the formoterol accounts for 0.2-2% (w/w), and the water-soluble carrier accounts for 99.8-98% (w/w); the water soluble carrier is one or more of lactose, mannitol or leucine.
8. The method for preparing the inhalation aerosol powder for treating asthma according to any one of claims 1 to 7, characterized by comprising the steps of:
1) the preparation of the carrier micro powder comprises the following steps:
(1) one or more of physiologically acceptable sugar, polyalcohol and amino acid is prepared into 0.1g/100ml to saturated aqueous solution,
(2) the solution is atomized into fine droplets,
(3) spraying the mixture into an organic solvent to form a mixture,
(4) drying;
2) the preparation of the medicine carrying micro powder comprises the following steps:
(1) formoterol and a water-soluble carrier are dissolved in water, the solute content in the solution is 1-10g/100ml,
(2) spray drying the solution;
3) the preparation of the andrographolide micropowder comprises the following steps:
(1) dissolving andrographolide micropowder and water soluble carrier in water to obtain solution with solute content of 1-10g/100ml,
(2) spray drying the solution;
4) mixing the carrier micropowder, the medicine carrying micropowder and the andrographolide micropowder by equivalent gradual addition method to obtain the preparation.
9. The process for preparing an inhalation aerosol powder for asthma according to claim 8, wherein: in the step 2) (1), the solute content in the solution is 2-7g/100 ml.
10. The process for preparing an inhalation aerosol powder for asthma according to claim 8, wherein: the organic solvent in step 1) (3) is selected from one or more of ethanol, isopropanol, acetone, n-butanol, sec-butanol, ethyl acetate, butyl acetate, tert-butyl methyl ether, ethyl formate, n-heptane, isobutyl acetate, isopropyl acetate, methyl acetate, butanone, methyl isobutyl ketone, isobutanol, n-pentane, n-pentanol, n-propanol and petroleum ether.
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| CN101342155A (en) * | 2007-07-11 | 2009-01-14 | 天津帝士力投资控股集团有限公司 | (R,R)-formoterol inhalation dust cloud agent and preparation method thereof |
| CN102481284A (en) * | 2009-03-24 | 2012-05-30 | 新加坡国立大学 | Use of andrographolide compounds for treating inflammation and airway disorders |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101342155A (en) * | 2007-07-11 | 2009-01-14 | 天津帝士力投资控股集团有限公司 | (R,R)-formoterol inhalation dust cloud agent and preparation method thereof |
| CN102481284A (en) * | 2009-03-24 | 2012-05-30 | 新加坡国立大学 | Use of andrographolide compounds for treating inflammation and airway disorders |
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