CN103505417A - 1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride aerosol and preparation method thereof - Google Patents
1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride aerosol and preparation method thereof Download PDFInfo
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- CN103505417A CN103505417A CN201210197827.7A CN201210197827A CN103505417A CN 103505417 A CN103505417 A CN 103505417A CN 201210197827 A CN201210197827 A CN 201210197827A CN 103505417 A CN103505417 A CN 103505417A
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Abstract
The invention discloses a 1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride aerosol and a preparation method thereof. A 1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride aerosol formula contains the following components by weight: 0.05-20% of 1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride, 0-20% of co-solvent, 0-2% of surfactant, and 60-99.95% of propellent. A preparation method contains the following steps of: according to the formula, uniformly mixing the 1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride, the co-solvent and the surfactant, adding a mixture into an aerosol enclosed container, and then pressing the propellent in, to complete the preparation. The 1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride aerosol has good bioavailability.
Description
Technical field
The present invention relates to a kind of 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol and preparation method thereof.
Background technology
In prior art, report 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime and salt thereof can prevent and treat the fibrotic disease of some internal organs, but, the drug effect of relevant aerosol is unsatisfactory, and bioavailability is extremely low, for maximizing, effectively utilize this medicine, this present situation is urgently to be resolved hurrily.
Summary of the invention
Technical problem to be solved by this invention is to have overcome existing 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] drug effect of-1-acetone oxime and salt aerosol thereof is unsatisfactory, and the defect that bioavailability is extremely low, provides a kind of 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl with good biological availability] phenyl]-1-acetone oxime hydrochlorate aerosol and preparation method thereof.
1-[4-[3-amino-4-hydroxy-3-of the present invention (methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol formulations contains 0.05%～20%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 0%～20% cosolvent (claiming again " cosolvent "), 0%～2% surfactant and 60%～99.95% propellant, and percentage ratio accounts for 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl for each composition] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount.
In the present invention, described 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate is 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl described in the routine of this area] phenyl]-1-acetone oxime hydrochlorate, commercially available obtain or according to this area conventional method by 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime raw material extracts and obtains.
In the present invention, described cosolvent is the cosolvent that the conventional aerosol in this area is used, and is preferably one or more in ethanol, isopropyl alcohol, propylene glycol and Polyethylene Glycol, is more preferred from one or more in ethanol, isopropyl alcohol, propylene glycol and Polyethylene Glycol.
In the present invention, described surfactant is the surfactant of the conventional aerosol in this area, as: sodium lauryl sulphate, sodium tetradecyl sulfate, sodium cetostearylsulphate, nonokynol-9-10, Hamposyl L, Hamposyl C, Semen Myristicae sarcosine, Hamposyl S, lauric isopropropanolamide, lauric acid diethyl amide, propylene glycol, propylene glycol diacetate, propylene glycol monostearate, Polyoxyethylene Sorbitan Monooleate, glycerol, isopropyl alcohol, lecithin, hydrolecithin, sodium lactate, stearic acid sodium lactate, lactic acid myristyl ester, lactic acid cetyl ester, sodium palmitate, polyvinyl alcohol, polysorbate-20, polysorbate-40, polysorbate-60, polysorbate-65, Polyoxyethylene Sorbitan Monooleate, polysorbate-85, polyoxyethylene lauryl ether, polyoxyethylene cetostearyl ether, polyoxyethylene (30EO) sorbitol 4 oleyl ethers, polyoxyethylene (40EO) sorbitol 4 oleyl ethers, polyoxyethylene (60EO) sorbitol 4 oleyl ethers, polyoxyethylene (60EO) sorbitol 4 stearyl ether, Emulsifier LT-60M, polyoxyethylene alkyl ether, emulsifying agent-BY, emulsifying agent-MoA, emulsifying agent-O, polyoxyethylene (10) oleyl ether, the hard ester ether of polyoxyethylene (8), the hard ester ether of polyoxyethylene (12), the hard ester ether of polyoxyethylene (24), the hard ester ether of polyoxyethylene (100), the hard ester ether of polyoxyethylene (110), the hard ester ether of polyoxyethylene (40), the hard ester ether of polyoxyethylene (50), polyoxyethylene (40) castor oil hydrogenated, polyoxyethylene (10) castor oil hydrogenated, polyoxyethylene (30) castor oil hydrogenated, polyoxyethylene (50) castor oil hydrogenated, polyoxyethylene (60) castor oil hydrogenated, polyoxyethylene (40) Oleum Ricini, polyoxyethylene (10) Oleum Ricini, polyoxyethylene (35) Oleum Ricini, polyoxyethylene (60) Oleum Ricini, polyoxyethylene (80) Oleum Ricini, polyoxyethylene (90) Oleum Ricini, polyoxyethylene (100) Oleum Ricini, the single oleyl ether of polyoxyethylene (300), the single oleyl ether of polyoxyethylene (400), the single oleyl ether of polyoxyethylene (600), sulphur flower Oleum Ricini, sulfonation castor oil hydrogenated, sodium dioctyl sulfosuccinate, dioctyl sulphosuccinate calcium and dioctyl sulphosuccinate potassium are preferably oleic acid, lecithin, one or more in poloxamer and sodium lauryl sulphate.
In the present invention, described propellant is the propellant that the conventional aerosol in this area is used, it is preferably tetrafluoroethane, heptafluoro-propane, dimethyl ether, carbon dichloride, liquid CO 2, dichlorodifluoromethane, Dichloromonofluoromethane, F-22, dichlorotetra-fluoroethane, one chloropentafluoroethane, chlorodifluoroethane, Difluoroethane, trichorotrifluoroethane, butane, Perfluorocyclobutane, isceon, one or more in hexane and propane, better is 1, 1, 1, 2-tetrafluoroethane, 1, 1, 1, 2, 3, 3, 3-heptafluoro-propane, one or more in trichorotrifluoroethane and dichlorodifluoromethane.
1-[4-[3-amino-4-hydroxy-3-of the present invention (methylol) butyl] phenyl]-1-acetone oxime aerosol formulations is preferably by 0.05%～20%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 0%～20% cosolvent, 0%～2% surfactant and 60%～99.95% propellant form, and percentage ratio accounts for 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl for each composition] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount.
1-[4-[3-amino-4-hydroxy-3-of the present invention (methylol) butyl] phenyl]-1-acetone oxime aerosol formulations preferably contains 2%～18%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 3%～15% cosolvent, 0.5%～2% surfactant and 65%～94% propellant, and percentage ratio accounts for 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl for each composition] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount.
1-[4-[3-amino-4-hydroxy-3-of the present invention (methylol) butyl] phenyl]-1-acetone oxime aerosol formulations is further preferably by 2%～18%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 3%～15% cosolvent, 0.5%～2% surfactant and 65%～94% propellant form, and percentage ratio accounts for 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl for each composition] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount.
Wherein, described cosolvent, surfactant and propellant are all as previously mentioned.
The invention still further relates to 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol one preferred embodiments is by 5%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 5% dehydrated alcohol, 1% oleic acid and 89%1,1,1,2-tetrafluoroethane forms, and percentage ratio is each composition 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount
1-[4-[3-amino-4-hydroxy-3-of the present invention (methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol can also contain conventional various other additives that add and other active substances in the conventional aerosol in this area, as long as it does not have antagonism or not appreciable impact aerosol effect of the present invention.
In the present invention, described 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol is solution aerosol or suspension aerosol.
1-[4-[3-amino-4-hydroxy-3-of the present invention (methylol) butyl] phenyl] preparation of-1-acetone oxime hydrochlorate aerosol Ke An this area conventional method, preferably preparation method comprises the steps: by described formula, by 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] after-1-acetone oxime hydrochlorate, cosolvent and surfactant evenly mix, add in aerosol hermetic container, be pressed into again afterwards propellant.
Wherein, described aerosol hermetic container is the conventional container that uses in this area.
Wherein, described 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] to use equipment be this area conventional equipment for the preparation of-1-acetone oxime hydrochlorate aerosol.
Agents useful for same of the present invention and raw material be commercially available obtaining all.
Meeting on the basis of this area general knowledge, each technical characterictic optimum condition above-mentioned in the present invention can combination in any obtain preferred embodiments.
Positive progressive effect of the present invention is: 1-[4-[3-amino-4-hydroxy-3-of the present invention (methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol has good biological availability, instant effect, good effect, taking convenience and untoward reaction are few, preparation method is easy, has market prospect and larger using value widely.
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The specific embodiment
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.
embodiment 1
Preparation method: by 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] after-1-acetone oxime hydrochlorate, cosolvent and surfactant evenly mix, add in aerosol hermetic container, be pressed into again afterwards propellant.
By with 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate compares (rat tail vein injection to the sample of SD rat vein administration simultaneously, visible " Nanfang Medical Univ's journal " 06 phase in 2009), 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl in gained aerosol] phenyl] bioavailability of-1-acetone oxime hydrochlorate is 25.5%.
embodiment 2
Preparation method: by 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] after-1-acetone oxime hydrochlorate, cosolvent and surfactant evenly mix, add in aerosol hermetic container, be pressed into again afterwards propellant.
By with 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate compares (rat tail vein injection to the sample of SD rat vein administration simultaneously, visible " Nanfang Medical Univ's journal " 06 phase in 2009), 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl in gained aerosol] phenyl] bioavailability of-1-acetone oxime hydrochlorate is 20.5%.
embodiment 3
Preparation method: by 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] after-1-acetone oxime hydrochlorate, cosolvent and surfactant evenly mix, add in aerosol hermetic container, be pressed into again afterwards propellant.
By with 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate is simultaneously to the sample of SD rat vein administration (rat tail vein injection, visible " Nanfang Medical Univ's journal " 06 phase in 2009) compare 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl in gained aerosol] phenyl] bioavailability of-1-acetone oxime hydrochlorate is 19.4%.
embodiment 4
Preparation method: by 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] after-1-acetone oxime hydrochlorate, cosolvent and surfactant evenly mix, add in aerosol hermetic container, be pressed into again afterwards propellant.
By with 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate is simultaneously to the sample of SD rat vein administration (rat tail vein injection, visible " Nanfang Medical Univ's journal " 06 phase in 2009) compare 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl in gained aerosol] phenyl] bioavailability of-1-acetone oxime hydrochlorate is 16.0%.
Claims (9)
1. a 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol, it is characterized in that: its formula contains 0.05%～20%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 0%～20% cosolvent, 0%～2% surfactant and 60%～99.95% propellant, percentage ratio accounts for 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl for each composition] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount.
2. 1-[4-[3-amino-4-hydroxy-3-as claimed in claim 1 (methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol, it is characterized in that: described 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime aerosol formulations is by 0.05%～20%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 0%～20% cosolvent, 0%～2% surfactant and 60%～99.95% propellant form, percentage ratio accounts for 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl for each composition] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount.
3. 1-[4-[3-amino-4-hydroxy-3-as claimed in claim 1 (methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol, it is characterized in that: described 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime aerosol formulations contains 2%～18%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 3%～15% cosolvent, 0.5%～2% surfactant and 65%～94% propellant, percentage ratio accounts for 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl for each composition] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount.
4. 1-[4-[3-amino-4-hydroxy-3-as claimed in claim 1 (methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol, it is characterized in that: described 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime aerosol formulations is by 2%～18%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 3%～15% cosolvent, 0.5%～2% surfactant and 65%～94% propellant form, percentage ratio accounts for 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl for each composition] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount.
5. 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl as described in claim 1 ~ 4 any one] phenyl]-1-acetone oxime hydrochlorate aerosol, it is characterized in that: described cosolvent is one or more in ethanol, isopropyl alcohol, propylene glycol and Polyethylene Glycol.
6. 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl as described in claim 1 ~ 4 any one] phenyl]-1-acetone oxime hydrochlorate aerosol, it is characterized in that: described surfactant is one or more in oleic acid, lecithin, poloxamer and sodium lauryl sulphate.
7. 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl as described in claim 1 ~ 4 any one] phenyl]-1-acetone oxime hydrochlorate aerosol, it is characterized in that: described propellant is 1,1,1,2-tetrafluoroethane, 1,1,1,2,3, one or more in 3,3-heptafluoro-propane, trichorotrifluoroethane and dichlorodifluoromethane.
8. 1-[4-[3-amino-4-hydroxy-3-as claimed in claim 1 (methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol, it is characterized in that: described 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate aerosol is by 5%1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl]-1-acetone oxime hydrochlorate, 5% dehydrated alcohol, 1% oleic acid and 89%1, 1, 1, 2-tetrafluoroethane forms, percentage ratio is each composition 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] mass percent of-1-acetone oxime hydrochlorate aerosol total amount.
9. 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl as described in claim 1 ~ 8 any one] phenyl] preparation method of-1-acetone oxime hydrochlorate aerosol, it is characterized in that: it comprises the steps: by described formula, by 1-[4-[3-amino-4-hydroxy-3-(methylol) butyl] phenyl] after-1-acetone oxime hydrochlorate, cosolvent and surfactant evenly mix, add in aerosol hermetic container, be pressed into again afterwards propellant.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210197827.7A CN103505417A (en) | 2012-06-15 | 2012-06-15 | 1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride aerosol and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210197827.7A CN103505417A (en) | 2012-06-15 | 2012-06-15 | 1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride aerosol and preparation method thereof |
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| CN103505417A true CN103505417A (en) | 2014-01-15 |
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| CN201210197827.7A Pending CN103505417A (en) | 2012-06-15 | 2012-06-15 | 1-[4-[3-amino-4-hydroxy-3-(hydroxymethyl)butyl]phenyl]-1-acetoxime hydrochloride aerosol and preparation method thereof |
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Application publication date: 20140115 |