CN105012278B - A kind of dry powder inhalation powder spray carrier sucrose and preparation method thereof - Google Patents
A kind of dry powder inhalation powder spray carrier sucrose and preparation method thereof Download PDFInfo
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- CN105012278B CN105012278B CN201510472628.6A CN201510472628A CN105012278B CN 105012278 B CN105012278 B CN 105012278B CN 201510472628 A CN201510472628 A CN 201510472628A CN 105012278 B CN105012278 B CN 105012278B
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Abstract
The invention belongs to drug carrier material technical field, discloses a kind of dry powder inhalation powder spray carrier sucrose and preparation method thereof.Methods described includes following preparation process：(1) then liquid glucose atomizing freeze drying is obtained into crystallite sucrose by the sucrose mass concentration soluble in water that is configured to for 20%~70% liquid glucose；(2) crystallite sucrose is scattered in ethanol solution, 1~60min is handled under ultrasound condition, filtered, dried, obtain dry powder inhalation powder spray carrier sucrose.The present invention can effectively prepare the crystallite sucrose for meeting medicament carrier demand using atomizing freeze drying technology, and surface modification is carried out to crystallite sucrose by ultrasonic technique and ethanol solution, adsorption and desorption beneficial to dust cloud agent carrier sucrose to medicament, products therefrom can significantly improve the operational efficiency of carrying medicament；And the present invention, using natural, cheap sucrose as raw material, cost is relatively low, has significant economic benefit.
Description
Technical field
The invention belongs to drug carrier material technical field, and in particular to a kind of dry powder inhalation powder spray carrier sucrose and its
Preparation method.
Background technology
The method of many treatment breathing problems is directly administered by respiratory tract, and it is advantageous in that dosage compares
Low, Small side effects and drug effect are fast, and no intestines and stomach enzymolysis and liver first-pass effect, medicine are made dry powder and solve difficulty
Dissolubility problem, and the stability of medicine can be kept etc..The physiological structure of lung has strict demand to the particle character of medicine, suction
Deposition site of the drug powder in respiratory tract and aerodynamic sizes, Size Distribution, shape and the density of its particle etc.
Parameter is closely related.Particle of the medicament particle diameter more than 10 μm may be adhered to upper respiratory tract position, the particle less than 0.5 μm
It can be breathed out with gas, and 1-8 μm of drug particles are considered to most effectively reach alveolar target location.
Traditional inhalation method can be damaged the ozone layer using propellant freon, had certain toxicity, can be caused branch
Airway constriction and cardiac arrhythmia etc., and after medicine is because being micronized, there is higher surface free energy, powder is easily gathered into
Group.At present gradually by more advanced powder spray dry powder inhalation (Dry powder inhalation aerosols, abbreviation
DPIs) substitute.Pharmaceutical carrier is mainly used in adsorbing drug microparticles in DPIs methods, stability of the enhancing medicine in storage, makes medicine
Thing keeps unformed glassy state.When the patient inhales, medicine is entered respiratory tract with pink mist through special doser, exhaling
Inhale is detached from the carrier medicine under shearing force caused by turbulent flow, and 1-8 μm of medicine enters lower respiratory tract and reaches target location
Effect locally or systemically is played, and bulky grain carrier (30-80 μm of diameter) then falls within oral cavity and throat, can solve to be used alone
Drug particle is because it has specific surface area big, poor fluidity, is easy to build up agglomerating the problem of leading to not effective inhalation.
Existing widely used medicament carrier particulate processing method is the mechanical crushing methods such as ball milling, fluid energy mill, these processing
Method has randomness, it is difficult to control vector particle diameter distribution, form, than physical parameters such as table properties, but these changes are serious
The absorption between granule and separating property are affected, the minor alteration of carrier granular characteristic can cause powder spray character of use
With the great changes of drug effect.In addition, different agents with different surfaces characteristic, it is necessary to have matched with different surfaces
The particulate vector of performance obtains similar aerodynamic feature.This is required in process to the particle shape of carrier
Can accurately it be controlled.The operational efficiency of DPIs methods is confined to 10-30% at present, and carrier problem turns into limitation dry powder inhalation
The bottleneck problem that technology further develops.
The carrier of FDA (Food and Drug Adminstration) (FDA) approval at present only has lactose, is used in commercially available Foradil Aerolizer formoterol fumarate
Be substantially lactose monohydrate.Major defect is that a part of medicine is strongly bound on lactose microcrystal surface, it is impossible to is being inhaled
Discharged in gas circulation；And lactose is processed refinement and obtained from lactogenesis, there is the danger for carrying crazy heifer disease virus.FDA is being at present
Make the research of deep layer to lactose limitation and endotoxin problem, while people replace the exploitation of carrier also to be got over inquiring into lactose
Come more.The research and development of Nantural non-toxic Sucrose Transporters with powdery are the focuses in current medicine dust cloud agent carrier field
Proposition.
The content of the invention
In order to solve the shortcomings that above prior art and weak point, primary and foremost purpose of the invention is to provide a kind of dry powder
The preparation method of inhalation powder spray carrier sucrose.
Another object of the present invention is to provide a kind of dry powder inhalation powder spray carrier sugarcane being prepared by the above method
Sugar.
The object of the invention is achieved through the following technical solutions：
A kind of preparation method of dry powder inhalation powder spray carrier sucrose, comprises the following steps：
(1) by the sucrose mass concentration soluble in water that is configured to for 20%~70% liquid glucose, then by liquid glucose spray chilling
It is dried to obtain crystallite sucrose；
(2) crystallite sucrose is scattered in ethanol solution, 1~60min is handled under ultrasound condition, filtered, dried, obtain
Dry powder inhalation powder spray carrier sucrose.
Preferably, the sucrose described in step (1) refers to that Sucrose is more than or equal to the white granulated sugar of 99.8% (mass fraction).
Preferably, the cryogenic temperature of the atomizing freeze drying is -15~-60 DEG C.
Preferably, described crystallite sucrose refers to that more than 90% grain diameter is 30~80 μm of crystallite sucrose.
Preferably, the ethanol solution described in step (2) refers to that the ethanol that the volumetric concentration of ethanol is 90%~99% is molten
Liquid.
Preferably, the mass volume ratio of the crystallite sucrose and ethanol solution is 1:(5~20).
Preferably, described ultrasound condition refers to：0.1~10W/cm of ultrasound intensity2, supersonic frequency 2 × 104~2 ×
109Hz。
Preferably, described drying refers to dry to water content≤0.01% of product.
Preferably, described drying refers to be dried by vibrated fluidized bed.
A kind of dry powder inhalation powder spray carrier sucrose, is prepared by above method.
The present invention preparation method and resulting product has the following advantages that and beneficial effect：
(1) present invention can effectively prepare the crystallite sucrose for meeting medicament carrier demand using atomizing freeze drying technology, and
The appearance of particle hardened phenomenon during traditional drying can be avoided；
(2) present invention carries out surface modification with ultrasonic technique and ethanol solution to crystallite sucrose, beneficial to dust cloud agent carrier sugarcane
Adsorption and desorption of the sugar to medicament；
(3) present invention prepares dry powder inhalation powder spray medicament carrier, the product of preparation by raw material of natural, cheap sucrose
It is safe to use, cheap, beneficial to popularization and application, there is significant economic benefit.
Brief description of the drawings
Fig. 1 is the SEM figures on the dry powder inhalation powder spray carrier sucrose surface that the embodiment of the present invention 3 obtains.
Embodiment
With reference to embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are unlimited
In this.
Embodiment 1
(1) take the white granulated sugar 200g for being divided into 99.8% containing sucrose to be put into container, then add 800g water, stirring is molten
Solution, is pumped into atomizing freeze drying equipment by the liquid glucose of preparation by peristaltic pump device and crystallite sucrose is prepared；Wherein spray cold
Lyophilized dry cryogenic temperature is -15 DEG C；
(2) the crystallite sucrose for taking 10g to prepare is put into the solution of 50mL concentration of alcohol 90% (v/v), is opened ultrasonic wave and is set
Standby, ultrasound condition is：Ultrasound intensity 0.1W/cm2, supersonic frequency 2 × 104Hz；After sonication treatment time 60min, filtering, pass through
Vibrated fluidized bed is dried, and the water content for drying products obtained therefrom is 0.008%, that is, obtains the loose dry powder of particle and inhale
Enter dust cloud agent carrier sucrose.
It is 30 μm of -80 μ that the crystallite sucrose that the present embodiment step (1) obtains detects its particle size range by online granularity equipment
M total number of particles accounts for more than the 95% of total particle number.
The pulmonary deposition ratio of powder spray is determined according to the method disclosed in 2005 editions annex XH of Chinese Pharmacopoeia, as a result table
Bright, the medicament lung sedimentation rate using the dry powder inhalation powder spray carrier sucrose of the present embodiment as carrier is 32.5%.
Embodiment 2
(1) take the white granulated sugar 200g for being divided into 99.8% containing sucrose to be put into container, then add 200g water, stirring is molten
Solution, is pumped into atomizing freeze drying equipment by the liquid glucose of preparation by peristaltic pump device and crystallite sucrose is prepared；Wherein spray cold
Lyophilized dry cryogenic temperature is -60 DEG C；
(2) the crystallite sucrose for taking 10g to prepare is put into the solution of 100mL concentration of alcohol 95% (v/v), is opened ultrasonic wave and is set
Standby, ultrasound condition is：Ultrasound intensity 10W/cm2, supersonic frequency 2 × 109Hz；After sonication treatment time 30min, filtering, by shaking
Fluidized bed to be dried, the water content for drying products obtained therefrom is 0.009%, that is, obtains the loose dry powder suction of particle
Dust cloud agent carrier sucrose.
It is 30 μm of -80 μ that the crystallite sucrose that the present embodiment step (1) obtains detects its particle size range by online granularity equipment
M total number of particles accounts for more than the 92% of total particle number.
The pulmonary deposition ratio of powder spray is determined according to the method disclosed in 2005 editions annex XH of Chinese Pharmacopoeia, as a result table
Bright, the medicament lung sedimentation rate using the dry powder inhalation powder spray carrier sucrose of the present embodiment as carrier is 35.2%.
Embodiment 3
(1) the white granulated sugar 200g for being divided into 99.8% containing sucrose is taken to be put into container, then addition 85g water, stirring and dissolving,
The liquid glucose of preparation is pumped into by atomizing freeze drying equipment by peristaltic pump device crystallite sucrose is prepared；Wherein spray chilling is done
Dry cryogenic temperature is -35 DEG C；
(2) the crystallite sucrose for taking 10g to prepare is put into the solution of 200mL concentration of alcohol 99% (v/v), is opened ultrasonic wave and is set
Standby, ultrasound condition is：Ultrasound intensity 5W/cm2, supersonic frequency 2 × 106Hz；After sonication treatment time 1min, filtering, pass through vibration
Fluid bed is dried, and the water content for drying products obtained therefrom is 0.008%, that is, obtains the loose dry powder suction powder of particle
Mist agent carrier sucrose.
It is 30 μm of -80 μ that the crystallite sucrose that the present embodiment step (1) obtains detects its particle size range by online granularity equipment
M total number of particles accounts for more than the 96% of total particle number；ESEM (SEM) figure on its surface is as shown in Figure 1.
The pulmonary deposition ratio of powder spray is determined according to the method disclosed in 2005 editions annex XH of Chinese Pharmacopoeia, as a result table
Bright, the medicament lung sedimentation rate using the dry powder inhalation powder spray carrier sucrose of the present embodiment as carrier is 33.6%.
Above-described embodiment is the preferable embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any Spirit Essences without departing from the present invention with made under principle change, modification, replacement, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
Claims (8)
- A kind of 1. preparation method of dry powder inhalation powder spray carrier sucrose, it is characterised in that：Including following preparation process：(1) by the sucrose mass concentration soluble in water that is configured to for 20%~70% liquid glucose, then by liquid glucose atomizing freeze drying Obtain crystallite sucrose；Described crystallite sucrose refers to that more than 90% grain diameter is 30~80 μm of crystallite sucrose；(2) crystallite sucrose is scattered in ethanol solution, 1~60min is handled under ultrasound condition, filtered, dried, obtain dry powder Inhalation powder spray carrier sucrose；Described ultrasound condition refers to 0.1~10W/cm of ultrasound intensity2, supersonic frequency 2 × 104~2 × 109Hz。
- A kind of 2. preparation method of dry powder inhalation powder spray carrier sucrose according to claim 1, it is characterised in that：Step (1) sucrose described in refers to the white granulated sugar of Sucrose >=99.8%.
- A kind of 3. preparation method of dry powder inhalation powder spray carrier sucrose according to claim 1, it is characterised in that：It is described The cryogenic temperature of atomizing freeze drying is -15~-60 DEG C.
- A kind of 4. preparation method of dry powder inhalation powder spray carrier sucrose according to claim 1, it is characterised in that：Step (2) ethanol solution described in refers to that the volumetric concentration of ethanol is 90%~99% ethanol solution.
- A kind of 5. preparation method of dry powder inhalation powder spray carrier sucrose according to claim 1, it is characterised in that：It is described The mass volume ratio of crystallite sucrose and ethanol solution is 1:(5~20).
- A kind of 6. preparation method of dry powder inhalation powder spray carrier sucrose according to claim 1, it is characterised in that：It is described Drying refer to dry to product water content≤0.01%.
- A kind of 7. preparation method of dry powder inhalation powder spray carrier sucrose according to claim 1, it is characterised in that：It is described Drying refer to be dried by vibrated fluidized bed.
- A kind of 8. dry powder inhalation powder spray carrier sucrose, it is characterised in that：Pass through the method described in any one of claim 1~7 It is prepared.
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| CN109266310A (en) * | 2018-11-08 | 2019-01-25 | 黄山九星环保科技有限公司 | A kind of non-chlorine of environment-friendly biomass is except ice and snow melting agent and preparation method thereof |
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| FI116657B (en) * | 2002-03-28 | 2006-01-31 | Focus Inhalation Oy | Method for treating carrier particles and their use |
| CN101239996B (en) * | 2008-01-04 | 2010-10-27 | 华南理工大学 | Method for preparing high shearing force microcrystal lactose |
| CN102858326A (en) * | 2010-04-01 | 2013-01-02 | 奇斯药制品公司 | Process for preparing carrier particles for dry powders for inhalation |
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| Title |
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| "影响干粉吸入剂肺沉积的制剂因素";王晓波等;《中国新药杂志》;20101231;第19卷(第7期);第580-583页 * |
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Address after: 510316 Guangdong, Guangzhou Province, No. 10, No. Applicant after: Guangdong Province Institute of Biological Engineering (Guangzhou Sugarcane Industry Research Institute) Address before: 510316 Guangdong, Guangzhou Province, No. 10, No. Applicant before: Guangzhou Sugarcane Industry Research Institute |
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Granted publication date: 20171229 Termination date: 20190804 |