CN101822654A - Pentetate inhalant - Google Patents
Pentetate inhalant Download PDFInfo
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- CN101822654A CN101822654A CN201010180144A CN201010180144A CN101822654A CN 101822654 A CN101822654 A CN 101822654A CN 201010180144 A CN201010180144 A CN 201010180144A CN 201010180144 A CN201010180144 A CN 201010180144A CN 101822654 A CN101822654 A CN 101822654A
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- pentetate
- inhalant
- powder
- spray
- pentetic acid
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Abstract
The invention discloses a pentetate inhalant. The pentetate is selected from calcium trisodium pentate and zinc trisodium pentate. The pentetate inhalant is selected from a pentetate aerosol, a pentetate spray and a pentetate powder (a dry powder inhalant). The pentetate inhalant is characterized in that the pentetate inhalant can inhale the pentetate through a lung to directly act on the lung inhaling radionuclides and directly complex with the radionuclides, and the pentetate inhalant is coughed out or absorbed in blood to be discharged by a kidney, thereby effectively clearing the radionuclides including lanthanum, cerium, praseodymium, neodymium, promethium, zirconium, niobium, and plutonium, which are deposited in the lung; and while the lung inhales the pentetate inhalant into the blood to complex with the radionuclides in the blood to be discharged by the kidney, thereby effectively clearing systemic contamination. The pentetate inhalant can be conveniently carried and used.
Description
Technical field
The present invention relates to medical field and radiation medicine field, particularly a kind of Pentetate inhalant.
Background technology
Pentetic acid is a kind of chelating agent, the chemical name diethylene-triamine pentaacetic acid.The form of its main clinical use is its two kinds of salt: pentetic acid trisodium calcium and pentetic acid trisodium zinc.They in vivo can be optionally and the radioactivity actinium series nucleic of internal deposition, as lanthanum (
140La), cerium (
144Ce), praseodymium (
143Pr), neodymium (
147Nd), promethium (
147Pm), zirconium (
95Zr), niobium (
95Nb) and plutonium (
239Cation combination such as Pu) forms the stable meltable complex, excretes through kidney soon, thereby has reduced body radioactivity nucleic deposition.Present dosage form is pentetic acid trisodium calcium injection and pentetic acid trisodium zinc injection, and specification is 5ml:500mg, and using method is intramuscular injection, every day 500mg, 1 day 1 time.These two kinds of injection obtained the U.S. FDA official approval in 2004.
Often discharge the aerosol that contains multiple radionuclide in the nuclear accident, The book of Changes lung sucks and enters human body.Radionuclide concentration obviously increases in air, might make to suck nucleic above ALI.Confirm that through zoopery pentetic acid trisodium calcium injection and pentetic acid trisodium zinc injection suck in the lung by atomising device, can obviously reduce plutonium deposition in vivo and injection plutonium deposition in vivo in sucking lung.But the interior plutonium of body that vein or abdominal cavity pentetic acid trisodium calcium injection or pentetic acid trisodium zinc injection can only reduce due to the non-inhalation route pollutes, and can not reduce the deposition of plutonium in lung.But pentetic acid trisodium calcium injection and pentetic acid trisodium zinc injection are not special pulmonary inhalation types, are difficult to obtain effective pulmonary drug deposition and distribute, and can not sell on market and use for the patient as pulmonary administration preparation commodity simultaneously.
Summary of the invention
The invention discloses a kind of Pentetate inhalant.Pentetate inhalant can suck pentetate by lung, directly acts on the pulmonary that sucks radionuclide, with the direct complexing of radionuclide, by expectoration or absorb in the blood and discharge through kidney, removes pulmonary effectively and pollutes.Lung sucks Pentetate inhalant simultaneously, also can with the radionuclide generation complexing in the blood, discharge through kidney by absorbing in the blood, removes whole body effectively and pollutes.
Pentetate inhalant among the present invention, the pentetate that wherein contains are selected from pentetic acid trisodium calcium, pentetic acid trisodium zinc.Pentetic acid trisodium calcium, pentetic acid trisodium zinc can be buied from the market, also can obtain corresponding pentetate, obtain pentetic acid trisodium calcium, pentetic acid trisodium zinc respectively as pentetic acid and corresponding sodium hydroxide, calcium oxide, zinc oxide reaction by pentetic acid processing.
Pentetate inhalant among the present invention, dosage form are selected from aerosol, spray, powder spray, promptly are selected from pentetate aerosol, pentetate spray, pentetate powder spray, and preferred dosage form is a powder spray, i.e. the pentetate powder spray.Powder spray is also referred to as Foradil Aerolizer formoterol fumarate.
Pentetate aerosol among the present invention, preparation method can be with reference to professional book and document.Usually, pentetate is ground into powdered form, powder is suspended in the propellant, wherein can add suspending agent, and fill is in the quantitative aerosol device then.The technology that pentetic acid is pulverized comprises grinding, comminution by gas stream.Propellant is selected from dimethyl ether, carbon dioxide, lower paraffin hydrocarbon, halothane hydrocarbon, fluorochloroparaffins.Lower paraffin hydrocarbon is selected from propane, butane, iso-butane, hexane.The halothane hydrocarbon is selected from tetrafluoroethane, Difluoroethane, octafluoro iso-butane, seven fluoroethanes.Fluorochloroparaffins is selected from dichlorodifluoromethane, Dichloromonofluoromethane, F-22, dichlorotetra-fluoroethane, a chloropentafluoroethane, chlorodifluoroethane, isceon.Suspending agent is selected from phospholipid, cholate, poloxamer, tween, span, ethyl oleate, glycerol.
Pentetate spray among the present invention, preparation method can be with reference to professional book and document.Usually, pentetate is water-soluble, general buffer agent, osmotic pressure regulator, the absorption enhancer of adding in the water, fill is in quantitative spray device then.Buffer agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, ammonium carbonate, ammonium bicarbonate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen phosphate, dipotassium hydrogen phosphate, diammonium phosphate.The main effect of buffer agent is to keep spray pH value to a certain degree, to obtain medicine stability, administration, minimizing stimulus equivalence fruit.Osmotic pressure regulator is selected from glucose, sucrose, sodium chloride, mannitol, sorbitol.Absorption enhancer phospholipid, cholate, poloxamer, ethanol.Ethanol reduces viscosity in addition, reduces the effect of mist droplet particle size.Cholate is selected from sodium cholate, sodium deoxycholate, sodium taurocholate, sodium dehydrocholate, SODIUM CHENODIOL, sodium ursodexoxycholate, preferably from sodium cholate, sodium taurocholate.
Pentetate powder spray among the present invention, the committed step of its preparation are the preparations that is used to suck powder.Particle diameter has a direct impact the pulmonary deposition position of powder particle.Easily breathe out when generally particle is less than 0.5 micron, easily be deposited on alveolar in the time of 1～5 micron, be deposited on air flue in the time of 4～7 microns, easily be deposited on pars oralis pharyngis during greater than 7 microns with air-flow.Therefore particle diameter should not surpass 7～10 micrometer ranges.But too small particle is relatively poor in the respiratory tract internal mobility.Therefore the adjuvant that adds good fluidity sometimes carries drug particle and enters respiratory tract as carrier.The preparation method that is used to suck powder is selected from spray drying method, ground sieve method, recrystallization method, preferably spray drying method.With reference to relevant professional book and document, can design and obtain pentetate and be used to suck powder.
Pentetate powder spray among the present invention, when adopting spray drying method for preparation, preparation process comprises:
(1) pentetate, water soluble adjuvant is water-soluble, absorption enhancer is dissolved in ethanol;
(2) above-mentioned aqueous solution and alcoholic solution mix, and carry out spray drying on spray dryer, collect the powder that obtains;
(3) above-mentioned powder and moderate lubrication agent mixing, the fill capsule obtains the pentetate powder spray.
Water soluble adjuvant in the above-mentioned steps is selected from lactose, sucrose, glucose, mannitol, trehalose, polyvinylpyrrolidone, ammonium bicarbonate, leucine, glucosan, Polyethylene Glycol, preferably from lactose, sucrose, mannitol, trehalose, polyvinylpyrrolidone, more preferably lactose.Absorption enhancer is selected from phospholipid, cholate, poloxamer.Wherein cholate is selected from sodium cholate, sodium deoxycholate, sodium taurocholate, sodium dehydrocholate, SODIUM CHENODIOL, sodium ursodexoxycholate, preferably from sodium cholate, sodium taurocholate.Lubricant is selected from Polyethylene Glycol, magnesium stearate.The proportion of pentetate and water soluble adjuvant is 1: 0.1～1: 10, preferably from 1: 0.5～1: 5.Suck promoter and in whole suction powder, account for weight ratio＜10%, preferably from＜5%, more preferably from＜1%.
The pentetate powder spray for preparing, can incapsulate in advance or the aluminium foil bubble-cap in, insert special-purpose suction apparatus before use.Powder inhalation device all has production both at home and abroad, as the happy board capsule-type of the English medicated powder inhaler of Nanjing Zhongshi Chemical Product Co. Ltd.'s production.
Pentetate powder spray (comprising suction apparatus) is easy to carry, and (breathing inspires formula) simple to operate, reasonable price does not contain propellant.Dried powder has increased preparation stability, and has targeting, efficient, quick-acting, characteristics such as toxic and side effects is little.Medicine absorbs by enriching blood capillary under the respiratory mucosa, and drug absorption is rapid, and is rapid-action, good patient compliance, and toxic and side effects is little.
Pentetate powder spray among the present invention, when the preparation method that is used to suck powder when grinding sieve method, pentetate and adjuvant can be ground jointly, sieve with the above screen cloth of 200 orders then, obtain superfine granule, add lubricant then or do not add lubricant, in the fill capsule or the bubble-cap of packing into.
Pentetate powder spray among the present invention, when the preparation method that is used to suck powder is recrystallization method, select suitable and water mutual solvents, add in the pentetate aqueous solution, and constantly stir, pentetate is separated out with superfine granule gradually, adds lubricant then or does not add lubricant, in the fill capsule or the bubble-cap of packing into.Be selected from the poor solvent of pentetate with the water mutual solvents, specifically be selected from ethanol, methanol, propanol, isopropyl alcohol, n-butyl alcohol, acetone, oxolane, dioxane, dimethyl formamide, diethylformamide, dimethyl sulfoxide.
The specific embodiment
Embodiment 1. pentetic acid trisodium calcium aerosols
Get pentetic acid trisodium calcium through comminution by gas stream, obtain the powder of high degree of dispersion, examine under a microscope, most of particle is less than 10 microns.Get 1g pentetic acid trisodium calcium powder and add in the 15g tetrafluoroethane that dissolves 0.3g poloxamer P188, the pressurization fill adds dosing pump in the aerosol bottle, obtain pentetic acid trisodium calcium aerosol.The very thin particle of this aerosol ejection can be drawn in the lung.
Pentetic acid trisodium zinc aerosol preparation technology is with top identical.
Embodiment 2. pentetic acid trisodium zinc sprays
Get 25% pentetic acid trisodium zinc aqueous solution, add buffer agent phosphate, osmotic pressure regulator sodium chloride, absorption enhancer sodium deoxycholate, obtain the pentetic acid trisodium zinc spray of 250mg/ml.This spray adds in the quantitative sprayer unit, and spray effect is good, can suck in the lung.
Pentetic acid trisodium calcium spray preparation technology is with top identical.
Embodiment 3. pentetic acid trisodium calcium powder sprays
5g pentetic acid trisodium calcium, 5g lactose are dissolved in 20ml water, the 0.2g sodium taurocholate is dissolved in 5ml ethanol.Above-mentioned solution is mixed, add spray dryer rapidly and carry out the spray drying operation, wherein inlet temperature is 90～94 ℃, and leaving air temp is 60～62 ℃, and charging rate 5ml/min, compressed air require are 600NL/h.Obtain superfine particle, microscopically is observed, and most of particle is below 10 microns.Get the magnesium stearate of above-mentioned powder adding 1%, mixing, fill obtains pentetic acid trisodium calcium powder spray (Foradil Aerolizer formoterol fumarate) in No. 2 capsules.According to official method, measure its pulmonary deposition rate and reach 46%.During use, capsule is put into suction apparatus, puncture capsule, suck powder to pulmonary.
Pentetic acid trisodium zinc powder spray preparation technology is with top identical.
Claims (9)
1. Pentetate inhalant.
2. Pentetate inhalant as claimed in claim 1, the pentetate that wherein contains are selected from pentetic acid trisodium calcium, pentetic acid trisodium zinc.
3. Pentetate inhalant as claimed in claim 1 is selected from pentetate aerosol, pentetate spray, pentetate powder spray.
4. Pentetate inhalant as claimed in claim 1 is the pentetate powder spray.
5. Pentetate inhalant as claimed in claim 1 is the pentetate powder spray, and its preparation method is selected from spray drying method, ground sieve method, recrystallization method.
6. Pentetate inhalant as claimed in claim 1 is the pentetate powder spray, and its preparation method that is used to suck powder is a spray drying method.
7. Pentetate inhalant as claimed in claim 6, the step of spray drying method for preparation pentetate powder spray comprises:
(1) pentetate, water soluble adjuvant is water-soluble, absorption enhancer is dissolved in ethanol;
(2) above-mentioned aqueous solution and alcoholic solution mix, and carry out spray drying on spray dryer, collect the powder that obtains;
(3) above-mentioned powder and moderate lubrication agent mixing, the fill capsule obtains the pentetate powder spray.
8. Pentetate inhalant as claimed in claim 7, water soluble adjuvant is selected from lactose, sucrose, mannitol, trehalose, polyvinylpyrrolidone.
9. Pentetate inhalant as claimed in claim 7, absorption enhancer is selected from phospholipid, cholate, poloxamer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010180144A CN101822654A (en) | 2010-05-24 | 2010-05-24 | Pentetate inhalant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010180144A CN101822654A (en) | 2010-05-24 | 2010-05-24 | Pentetate inhalant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101822654A true CN101822654A (en) | 2010-09-08 |
Family
ID=42686961
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010180144A Pending CN101822654A (en) | 2010-05-24 | 2010-05-24 | Pentetate inhalant |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101822654A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009526853A (en) * | 2006-02-17 | 2009-07-23 | エスアールアイ インターナショナル | Oral DTPA for chelation of radionuclides |
-
2010
- 2010-05-24 CN CN201010180144A patent/CN101822654A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009526853A (en) * | 2006-02-17 | 2009-07-23 | エスアールアイ インターナショナル | Oral DTPA for chelation of radionuclides |
Non-Patent Citations (2)
| Title |
|---|
| 《Journal of Controlled Release》 20061206 C. Gervelas et al "Direct lung delivery of a dry powder formulation of DTPA with improved aerosolization properties : Effect on lung and systemic decorporation of plutonium" 第78-86页 1-9 第118卷, 第1期 2 * |
| 《世界临床药物》 20051231 孙华君等 "放射性核素体内沾染的治疗药物" 第113-116页 1-9 第26卷, 第2期 2 * |
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Open date: 20100908 |