CN104997731B - A kind of composition and the aerosol containing the composition - Google Patents
A kind of composition and the aerosol containing the composition Download PDFInfo
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Abstract
The present invention provides a kind of compositions and application thereof, it includes the component of following weight proportion：HFC-134a10~100 part, 5~50 parts of isopropyl myristate, 0.1~10 part of fumed silica.The present invention also provides a kind of aerosols and its preparation method and application, it includes the supplementary material of following weight proportion：5~20 parts of bulk pharmaceutical chemicals, HFC-134a10~100 part, 5~50 parts of isopropyl myristate, 0.1~10 part of fumed silica.The present invention also provides the purposes in the drug of aerosol skin ulcer caused by preparation treatment burn and scald, bedsore, diabetes.Aerosol prepared by the present invention has good suspension effect and emission rate, and quality is stablized, and convenient drug administration is quick, has a vast market foreground.
Description
Technical field
The present invention relates to a kind of composition and containing the aerosol of the composition, belong to drug field.
Background technique
Aerosol is a small dosage form in pharmacy, but has played uniqueness in real life and medicinal application practice
Effect, be well received.But in current practical application, the development of aerosol is faced with a most urgent, difficulty
The predicament of maximum problem, i.e. propellant freon substitution.
CFC (Chlorofluorocarbon) is also known as chlorofluoro-alkane or freon, due to its unique property and good
Driveability is cast, existing over half a century is widely applied in medicinal aerosol field.However, CFC breaks atmospheric ozone layer
Bad is one of great environmental problem of facing mankind.1987 sign Montreal Protocol to 5 kinds of CFC (11,12,113,
114,115) disabling timetable is proposed:In 2000, all disabling, developing country can be postponed 10 years for developed country.China is
In on January 1st, 2010, completely forbids and use CFC in aerosol products.Currently, CFC substitute mainly has (1) alkanes
Propellant；(2) dimethyl ether；(3) inertia compressed gas；(4) hydrofluoroalkane compounds.Hydrofluoroalkane compounds (HFC,
It Hydrofluorocarbon) is generally acknowledged most promising sub, HFC series propellant does not constitute pollution, toxicity to environment
It is low, carcinogenic teratogenesis and mutagenesis will not be generated.Its weak flammability improves the safety of product, reduce production storage at
This.The hydrofluoroalkane propellant for just quickly entering market at present mainly has HFC-134a (1,1,1,2- tetrafluoroethane) and HFC-
227ea (1,1,1,2,3,3,3- heptafluoro-propane).
But in practical applications, the substitution of CFC encounters some intractable technical problems.It is necessary to prepare suspension aerosol
Consideration prevents raw medicine powder from agglomerating and recrystallizing in aerosol system.Both phenomenons can cause drug in container or valve system
The delay of system and cause valve blocks or dosage inaccuracy.The generation of above-mentioned phenomenon in order to prevent, often by surfactant, increasing
Product agent and lubricant etc..However, by taking HFC-134a replaces CFC as an example, firstly, common surfactant in CFC aerosol, such as
Span85, oleic acid and Fabaceous Lecithin do not dissolve in HFC-134a, and it is to prepare aerosol especially that surfactant, which is dissolved in propellant,
The prerequisite of suspension aerosol.The limitation of this auxiliary material application is just the development band of the mixed type selecting aerosol of HFC system
Great difficulty is carried out.Furthermore in terms of the density of liquid, HFC-134a (1.29g/mL, 20 DEG C) also lower than CFC (1.33g/mL,
20 DEG C), it is also greatly increased to the biggish powder of density to be prepared into the difficulty of suspension aerosol of stable and uniform.Therefore,
The surfactant that solubility is good in HFC-134a is filtered out, exploitation can be used for the novel of the suspension aerosol of HFC system
Auxiliary material is a problem to be solved.
Solving for propellant substitution problem can be the more chances of survival and development creation of aerosol, enable aerosol
Its uniqueness and irreplaceability in clinical application is given full play to, especially in traditional Chinese medicine preparation field, Chinese medicine (is suspended
Type) for aerosol with unique advantage in terms of local treatment, convenient drug administration is quick, direct, it does not need to make by other equipment
With, and microbiological contamination is avoided in use process, stable product quality, compared with Western medicine external application dressing and traditional agent of external treatment with Chinese medicine
Type, such as creme, paste have incomparable advantage；Especially suitable for clinical treatment chronic surface ulcers, burn and scald, cotton-padded mattress
Skin ulcer caused by sore, diabetes etc., has a vast market foreground；But since Chinese medicine derives from animals and plants, mineral, also
It is related to the different Chinese medical extract of physicochemical property, Chinese medicine is prepared into aerosol, technical problem even more urgently to be resolved.
Summary of the invention
The technical solution of the present invention is to provide a kind of adjuvant compositions suitable for Chinese medicine suspension aerosol；This hair
There is provided the aerosols and the aerosol that prepare the composition and Chinese medicine or extract proportion for bright another technical solution
The preparation method and purposes of agent.
The present invention provides a kind of compositions, it contains the component of following weight proportion：
10~100 parts of HFC-134a, 5~50 parts of isopropyl myristate, 0.1~10 part of fumed silica.
Preferably, the weight proportion of component is：
HFC-134a50 parts, 20 parts of isopropyl myristate, 0.8 part of fumed silica.
The present invention provides the compositions to be used to prepare using HFC as the purposes of the suspension aerosol of propellant.
The present invention provides a kind of aerosol, the supplementary material including following weight proportion：
5~20 parts of bulk pharmaceutical chemicals, 10~100 parts of HFC-134a, 5~50 parts of isopropyl myristate, fumed silica
0.1~10 part；
Wherein, the bulk pharmaceutical chemicals contain calcined and quenched CALAMINA, calcined gypsum or forge mother-of-pearl.
Preferably, the weight proportion of supplementary material is：
10 parts of bulk pharmaceutical chemicals, 50 parts of HFC-134a, 20 parts of isopropyl myristate, 0.8 part of fumed silica.
Wherein, the bulk pharmaceutical chemicals dissipate for Huangshi；
The Huangshi, which dissipates, to be prepared by the raw material of following weight proportion：
10 parts of rheum officinale, 10 parts of the coptis, 10 parts of Cortex Phellodendri, 1~5 part of Resina Draconis, 5~25 parts of calcined and quenched CALAMINA, calcined gypsum 5~25
Part, 0.75~2.5 part of alum, 1 part of Pulvis Fellis Suis.
Wherein, the bulk pharmaceutical chemicals are following compositions 1 or composition 2：
Composition 1：150 parts of calcined and quenched CALAMINA powder, 80 parts of calcined gypsum powder forge 80 parts of Concha Margaritifera powder, 40 parts of alumen powder, frankincense
20 parts of powder, 20 parts of stir-baked MYRRHA powder；
Composition 2：6 parts of pearl, 9 parts of elephant hide, 9 parts of amber, 9 parts of keel, 9 parts of calomel mercurous chloride, 1.8 parts of borneol, is forged 3 parts of cow-bezoar
18 parts of sweet stone.
The present invention provides the methods for preparing above-mentioned aerosol, include the following steps：
A. the bulk pharmaceutical chemicals for taking prescription amount, beat powder or water or organic solvent extracts, and vacuum drying, dried object carries out Ultramicro-powder
It is broken, obtain bulk pharmaceutical chemicals Ultramicro-powder；
B. bulk pharmaceutical chemicals Ultramicro-powder is added in surfactant, and be uniformly mixed, add cosolvent, suspending agent, moisture
Regulator is uniformly mixed, obtains mixture；
C. mixture is packed into aerosol container, and pours into propellant, aerosol is made.
Wherein, the partial size of bulk pharmaceutical chemicals Ultramicro-powder made from a step is less than 100 μm, and moisture content is less than 9%.
The present invention also provides Huangshi to dissipate aerosol skin ulcer caused by preparation treatment burn and scald, bedsore, diabetes
Purposes in drug.
The present invention selects CFC optimum substituent HFC-134a as propellant, is screened by auxiliary material dissolubility, it was found that energy
The surfactant isopropyl myristate miscible with HFC-134a.Prescription is screened by single factor test and orthogonal test：
Pass through suspension effect preliminary screening, it was found that evenly dispersed in isopropyl myristate can form the suspending for stablizing suspension
Agent fumed silica；And by single factor experiment and orthogonal test, the optimum proportioning of aerosol prescription is obtained, has successfully solved
It has determined rapid subsidence problem of the drug powder in isopropyl myristate and propellant, has provided suitable for HFC system
The novel supplementary product compatibility of Chinese medicine suspension aerosol.
The present invention is using HFC-134a as propellant, and isopropyl myristate is as surfactant, vapor phase method titanium dioxide
Silicon as suspending agent, be added Huangshi that pharmaceutically acceptable auxiliary material is prepared dissipate aerosol have good suspension effect and
Emission rate, quality are stablized, and convenient drug administration is quick, particularly suitable for the burn and scald sufferer local administration of bed, has a vast market
Prospect.
Below by way of specific embodiment, the present invention is described in further detail, but is not intended to limit the present invention, ability
The various changes and replacement that field technique personnel make according to the present invention, as long as it does not depart from the spirit of the invention, should belong to this hair
Bright scope of the appended claims.
Specific embodiment
The preparation of the aerosol of the present invention of embodiment 1
(1) preparation of Huangshi powder ultramicro powder：
Raw material is weighed by following prescription amounts：
Rheum officinale 10kg, coptis 10kg, Cortex Phellodendri 10kg, Resina Draconis 5kg, calcined and quenched CALAMINA 25kg, calcined gypsum 25kg, alum
2.5kg, Pulvis Fellis Suis 1kg.
Preparation method：
A. rheum officinale, the coptis, Cortex Phellodendri are taken, is crushed, 10 meshes are crossed, 85% (v/v) alcohol reflux is added to extract, is filtered, filtrate is dense
It is reduced to the medicinal extract of relative density 1.10 (40 DEG C)；
B. Resina Draconis, calcined and quenched CALAMINA, calcined gypsum, alum, Pulvis Fellis Suis co-grinding are sieved with 100 mesh sieve；
C. a step medicinal extract is added in the co-grinding powder of b step, is mixed, 60 DEG C, vacuum drying makes moisture content
Less than 9%.Gained dried object is pulverized, and Huangshi powder ultramicro powder of the partial size less than 100 μm is made.
(2) preparation of aerosol：
Supplementary material is weighed by following weight proportions：
Huangshi powder ultramicro powder 10kg, HFC-134a 50kg, isopropyl myristate 20kg, fumed silica 0.8kg
Preparation method：Huangshi powder ultramicro powder is added in isopropyl myristate and is stirred evenly, colloid mill ground and mixed is crossed,
Fumed silica is added in mixture.Again through high-speed stirred, homogeneous paste mixture is formed, aerosol container is packed into, fills
Enter propellant HFC-134a, shakes, obtain 1000 tank of aerosol.
The preparation of the aerosol of the present invention of embodiment 2
Raw material is weighed by following prescription amounts：Pearl 6kg, cow-bezoar 3kg, elephant hide 9kg, amber 9kg, keel 9kg, calomel mercurous chloride 9kg,
Borneol 1.8kg, sweet stone 18kg is forged.
Preparation method：It takes above-mentioned raw materials medicine to be pulverized, takes 5kg parts of bulk pharmaceutical chemicals Ultramicro-powders that 12kg myristic acid is added
In isopropyl ester, 1kg fumed silica is added, is ground through colloid mill, formed homogeneous paste mixture, be packed into aerosol
Agent tank is filled with propellant HFC-134a, and shaking obtains 1000 tank of aerosol.
Beneficial effects of the present invention are proved below by way of specific experiment.
The screening test of the aerosol surfactant of the present invention of experimental example 1
(1) experimental method：
Since the difficulty for quantitative determining the solubility of surfactant in high pressure closed system is larger, this experiment uses mesh
The legal dissolubility for investigating each surfactant in HFC-134a of observation is surveyed, it is obvious that surfactant and HFC-134a, which divide,
Two-phase, be denoted as unmixing.In test with a small amount of determinand 1g is added in high pressure test tube, it is then charged with HFC-134a 10g, is shaken
It shakes, ultrasonic 30s, stands, observe the dissolubility of determinand.Solubility studies carry out in following a few class surfactants：
Brijis (polyethenoxy ether class), Tween (polyoxyethylene sorbitan fatty acid ester), Span (anhydro sorbitol fat acid
Ester), fatty acid ester, vegetable oil lipid.
(2) experimental result is shown in Table 1~3.
Dissolubility of 1 surfactant of table in HFC-134A
Note：It is apparent two-phase that surfactant and HFC-134a, which divide, is denoted as unmixing.
Dissolubility of the 2 moisturizing grease of table in HFC-134A
Dissolubility of 3 vegetable fat of table in HFC-134A
(3) experiment conclusion：
Surfactant must be dissolved in competence exertion in propellant well prevents raw medicine powder in aerosol system
The effect of cohesion and recrystallization.The experimental results showed that polyethenoxy ether class, polyoxyethylene sorbitan fatty acid ester, dehydration
Sorbierite fat acid esters and vegetable oil lipid cannot be miscible with HFC-134a.In aliphatic ester constituents, only myristic acid is different
Propyl ester (isopropyl myristate) and HFC-134a complete miscibility, but isopropyl laurate (lauric acid/dodecanoic acid isopropyl ester) that carbochain is shorter and
The longer isopropyl palmitate of carbochain (isopropyl palmitate) cannot be dissolved in HFC-134a again.Other fatty acid esters, or slightly
It can be dissolved in HFC-134a, but be used as aerosol since self property (such as freezing point is lower, or has irritation) is also unsuitable
Surfactant in agent.Therefore, the present invention select can be miscible with propellant HFC-134a isopropyl myristate as table
Face activating agent.
The screening test of the aerosol suspending agent of the present invention of experimental example 2
(1) experimental method
It weighs appropriate suspending agent to be added in isopropyl myristate, grinding uniformly, pours into observation suspension and sedimentation in graduated cylinder
Phenomenon.
(2) experimental result is shown in Table 4.
4 suspending agent suspending effect of table compares
(3) experiment conclusion：
In suspension aerosol system, when surfactant is only added, since medicinal powder density is larger, it can comparatively fast generate and divide
Layer phenomenon may cause medicinal powder agglomeration and be unfavorable for the stability of system, and settle it is too fast will lead to feed liquid it is canned when dosage
Inaccuracy.Therefore, it is necessary to which suspending agent is added in suspension aerosol system, enhance its stability.Common low molecule suspending
Agent is mostly polysaccharide component, and polarity is big, does not dissolve in HFC-134a.Semi-synthetic polymeric retention aid suspension also belongs to polysaccharide component, indissoluble
In HFC-134a.
This experiment is to being not required to dissolve, and only evenly dispersed thixotrope class suspending agent in the liquid phase is screened, experiment
The result shows that not only dosage is few for fumed silica, but also can generate apparent thixotropy after mixing with isopropyl myristate,
Suspension effect is best, other suspending agents suspension effect in isopropyl myristate is undesirable.Therefore, the present invention selects to be suspended
The optimal fumed silica of effect is as suspending agent.
3 drug powder of experimental example and isopropyl myristate ratio screening test
(1) experimental method：The drug Ultramicro-powder of regulated proportion is added in 50mL isopropyl myristate, is stirred evenly,
It is fitted into graduated cylinder and observes mobility and lamination.
(2) experimental result is shown in Table 5.
Influence of the 5 medicinal powder additional amount of table to feed solution flow
(3) experiment conclusion：
The dosage of surfactant directly affects the physical stability and dispersion performance of HFC-134a aerosol sample.Aerosol
When the filling production of agent, generally first the other components in addition to propellant are uniformly mixed, feed liquid is formed, pours into aerosol container, most
After be pressed into propellant.Therefore viscosity of sludge cannot be too big, in order to avoid influencing mobility, causes loading amount is uneven even can not be filling.Experiment
The result shows that feed liquid is sticky, and mobility is poor, no when the amount that the amount of feed liquid traditional Chinese medicine powder accounts for isopropyl myristate is more than 70%
Conducive to tinning.Therefore, it is 30~60% that the present invention, which selects optimal medicinal powder dosage,.
The dosage screening test of the aerosol suspending agent of the present invention of experimental example 4
(1) experimental method：It weighs that isopropyl myristate is appropriate, the fumed silica of different weight is added, grinding is stirred
It mixes uniformly, is fitted into test tube and observes.
(2) experimental result is shown in Table 6.
Influence of the 6 suspending agent additional amount of table to feed solution flow and suspension ability
(3) experiment conclusion：
The ratio of suspending agent directly affects the physical stability and dispersion performance of HFC-134a aerosol sample.Suspending agent is used
Amount should make feed liquid to be filled and it is filling after drug powder keep preferable suspended state, but dosage excessively will lead to feed liquid excessively
The canned and jeting effect of sticky influence.The experimental results showed that it is 2~6% that gas phase silica gel, which accounts for isopropyl myristate (IPM),
When, the mobility of feed liquid is preferable, does not settle, and is conducive to tinning.Therefore, it is 2~6% that the present invention, which selects optimal suspending agent ratio,.
The aerosol feed liquid of the present invention of experimental example 5 and propellant ratio screening test
(1) experimental method：Aerosol is added in the feed liquid of constant weight and tests high pressure test tube, it is closed, then from valve port pressure
Enter quantitative HFC-134a, shaking uniformly, is pressed《Chinese Pharmacopoeia》(2010 editions) one annex IZ lower prescriptive procedures, to each formula
Ratio carries out aerosol and sprays total amount investigation.
(2) experimental result is shown in Table 7.
7 feed liquid of table accounts for influence of the weight ratio to emission rate of propellant
(3) experiment conclusion：
Feed liquid and propellant have an optimal proportion in the case where total amount is certain, and feed liquid is very few, then every bottle of content of dispersion is few；Material
Liquid is excessive, then sprays not exclusively, cause to waste.The experimental results showed that when feed liquid loading amount accounts for 50% or less propellant loading amount, spray
Total amount is higher out.
The orthogonal test of the aerosol prescription optimum proportioning of the present invention of experimental example 6
(1) experimental method：
On the basis of single factor experiment, feed liquid accounts for the ratio of propellant, drug powder accounts for isopropyl myristate for investigation
Ratio, suspending agent account for the optimum proportioning condition of three factors of ratio of isopropyl myristate.It is suspended and is imitated with suspension aerosol
Fruit (sedimentation volume ratio), emission rate are judgment criteria, by weight ratio 1: 1, form comprehensive score, the evaluation index as prescription.
With L9(34) orthogonal trial testing program, using the time that is suspended, redisperse time and comprehensive grading value as index
It is tested, the results are shown in Table 9.
Comprehensive score=sedimentation volume ratio/sedimentation volume ratiomax× 100+ spray volume/spray volumemax×100
The measurement of sedimentation volume ratio：Feed liquid is packed into aerosol and tests high pressure test tube, quantitative propellant is poured into, makes feed liquid
Reach corresponding test requirements document to propellant ratio.Firmly after shaking uniformly, the beginning height H of suspended matter is write down0, 3 hours are stood,
The final height H for writing down suspended matter, is calculated as follows：
Sedimentation volume ratio=H/H0
The measurement of emission rate：
Emission rate=(W1-W2)/(W1-W0) × 100%
W1- spray aerosol former gross weight；W2- spray rear tank weight；W0- slack tank weight
(2) experimental result：
8 orthogonal test factor level table of table
9 orthogonal experiments of table
(3) experiment conclusion：
In terms of the extreme value R of orthogonal test, RA>RB>RC, show to influence A factor-feed liquid additional amount in 3 factors of formula
It is maximum to formula physics stability influence, it is the formula factors of most critical.Comprehensive score is to be formulated A3B2C2It is optimal.Gas of the present invention
The optimum formula of mist agent is：Feed liquid additional amount accounts for the 60% of propellant total amount, and medicinal powder additional amount accounts for Surfactant Ratio and is
50%, it is 4% that suspending agent additional amount, which accounts for Surfactant Ratio,.
The aerosol of the present invention of experimental example 7 tests the Effect study of diabetes rat foot ulcers
(1) experimental material
Reagent and drug：Streptozotocin, Huangshi dissipate aerosol (preparing according to embodiment 1)
Experimental animal：125 6 week old male Wistar rats, cleaning grade, weight (190~210) g, by Sichuan Province's Chinese medicine
Medicine academy of sciences Experimental Animal Center provides.
(2) experimental method
Animal is randomly divided into blank control group 10, remaining animal fasting 16h, by streptozotocin (STZ) 55mg
kg-1, use 0.1molL-1Citrate buffer solution (pH4.2) is made into 1% solution, and (ip) is injected intraperitoneally and causes the high blood of rat
Sugar measures fasting blood-glucose after 7d>16.6mmol·L-1As the standard of diabetes Cheng Mo, animal divides 5 groups at random, and every group 11,
(1) blank control group (distilled water)；(2) model group；(3) Huangshi dissipates aerosol low dose (0.81gkg-1) group；(4) Huangshi dissipates
Aerosol middle dosage (1.62gkg-1) group；(5) Huangshi dissipates aerosol large dosage (3.24gkg-1) group.(1)~(5) each group
Animal respectively makes a surface of a wound in backbone two sides after back is lost hair or feathers with surgical method, and diameter is about the circle of (18~20) mm
Shape skin injury face, is deep to fascia, starts medication from next day, and continuous 14 days.It is discussed for 24 hours with medical pathologies graphical analysis after last medicine
Measure surface of a wound area, calculate Wound healing rate (%)=(original surface of a wound area-do not heal surface of a wound area)/original surface of a wound area ×
100%.
(3) experimental result
10 each group rat ulcer healing rate of table compares
Compared with model group (t inspection)：*p<0.05, * * p<0.01,
(4) experiment conclusion
Huangshi dissipates the high, medium and low dosage group ulcer healing rate of aerosol compared with model group, and there are significant difference, 14d in when 7d
When have extremely significant sex differernce, it was demonstrated that Huangshi of the present invention dissipate aerosol to skin ulcer caused by wound have significant curative effect.
The aerosol of the present invention of experimental example 8 tests the Effect study of rat bedsore
(1) experimental material
Male rat, 180~200g of weight are provided by Sichuan Provincial Academy of Traditional Chinese Medicine Experimental Animal Center, Huangshi air-dispersing
Mist agent (is prepared) according to embodiment 1,0.9% sodium chloride injection.
(2) experimental method
Animal packet：44 rats are divided into four groups, every group 11, by weight size sequencing numbers, by random numbers table
Method is randomly divided into saline control group and Huangshi dissipates 10%~40% group of aerosol.
Animal model creation：Rat is anaesthetized respectively, skin degerming, fixed with prone position, close to back backbone
Left side cut an openning for being about 3cm, implantation is through autoclaved 4.0cm × 2.5cm × 0.05cm stainless-steel sheet, suture
Notch, and bind up a wound, it is fixed with bandage.The postoperative single cage of rat is fed, and ld is observed.For 24 hours afterwards with 4.0cm × 2.25cm ×
1.0cm magnet oppresses the surface of a wound (5h/d), and rest 12h is recycled l times, total pressing time 10h, records formation area and the indexing of bedsore
Grade.Individually divide animal to cage, feeds and management condition is consistent.
Test method：Rat bedsore model forms 2nd day latter, the control rats physiological saline cleaning surface of a wound.Medicine group
Rat first with physiological saline clean the surface of a wound, further according to surface of a wound size smear Huangshi dissipate aerosol normal saline dilution liquid (10~
40%)；Each group bedsore treats 14d, then judges effect.
Observation index：According to bedsore staging scale, cure as the disappearance of sore face, epidermis healing；Improving is that the surface of a wound reduces 80%,
Granulation is fresh, grows, edema extinction, and sepage is few；It is small by 50% for sore reduction of area in vain, granulation undergrowth or there is purulence sepage.
(3) experimental result
11 two groups of rats of table effect that treats patients with decubitus compares
Note：(t inspection) the * * P < 0.01 compared with model group
(4) experiment conclusion
As seen from the experiment, high, medium and low three groups of the average healings and the obvious shortening (P of model group<0.01),
Prove that the present invention has significant curative effect to skin ulcer caused by bedsore.
The aerosol extracorporeal bacteria inhibitor test of the present invention of experimental example 9
(1) experimental material
Huangshi dissipates aerosol (preparing according to embodiment 1)；Strain Escherichia coli, salmonella, staphylococcus aureus mould
Formula bacterial strain is provided by the identification of Chinese pharmaceutical biological product；Culture medium：Ordinary nutrient agar (lot number 20140402), common battalion
Support broth bouillon (lot number：20131114), it is purchased from Beijing extensive and profound in meaning star biotechnology Co., Ltd.
(2) experimental method
The preparation of test drug：Take Huangshi to dissipate aerosol ejecta, with normal saline at concentration be 0.5,1,2g/mL
Medical fluid, filtering, flowing steam sterilization 20min, 4 DEG C of preservations are spare.
The preparation of strain suspensions：Plain agar is inoculated in the freeze-drying lactobacillus that oese picks them separately this 3 kinds of type strains
On culture medium, it is placed in 16~18h of incubation in 37 DEG C of constant incubators, then picking single bacterium colony is inoculated in 100mL (300mL taper
Bottle) in broth bouillon, shaken cultivation case (37 DEG C, 200r/min) activates 6~8h, and colony counting method carries out bacterium colony counting, with
Clump count 30~300 be standard determination bacterium solution extension rate, with sterile saline by bacterium solution dilution turbidity be 2 ×
107CFU/mL is spare.
Huangshi dissipates the determination of aerosol Mlc：With reference to lysoplate assay (Beating holes method) and make suitably to change
Into primary election medical fluid maximum Mlc.High (2g/mL), in (1g/mL), low 3 repetitions of (0.5g/mL) every kind of concentration.Determine mark
It is quasi-：It is extremely quick：Antibacterial circle diameter > 20mm；Gao Min：15~20mm of antibacterial circle diameter；In it is quick：10~15mm of antibacterial circle diameter；It is low
It is quick：Antibacterial circle diameter < 10mm；No inhibition zone is drug resistance.
Minimal inhibitory concentration measurement：It takes sterilizing teat glass 11 and numbers, every test tube is previously added sterile broth cultivation
Base 2.0mL is supported, and tested Chinese medicine (1g/mL) 2.0mL of sterilizing is added in the 1st pipe, is mixed, is then taken out 2.0mL and be put into the 2nd
In branch test tube, successively doubling dilution then takes out 2.0mL and discards until the 9th pipe.Test medicine is not added in 10th pipe, as sun
Property control.In 11st pipe plus the tested Chinese medicine 2.0mL of sterilizing, mixing then take out 2.0mL and discard, be added without bacterium, as feminine gender
Control.1~10 each pipe is added for trying bacterium solution 0.1mL, so that the final bacterial concentration of every pipe is 106CFU/mL L.Respectively manage parallel 3
Part.It after 37 DEG C of cultures for 24 hours, draws meat soup 0.1mL in each test tube and is coated on nutrient agar panel, 37 DEG C of culture 16~18h are sterile
The liquor strength of long test tube of being born is MIC.
(3) experimental result
Bacteriostatic test result of the 12 Huangshi aerosol of table to type strain in 3
13 minimal inhibitory concentration result of table
Note：, asepsis growth；+, there is bacterium growth
(4) experiment conclusion
As shown in Table 12, scattered high, medium and low 3 concentration of aerosol medical fluid of Huangshi of the present invention is in staphylococcus aureus
Extremely quick, middle concentration antibacterial circle diameter is 29.0mm；Huangshi dissipate high and low two concentration of aerosol to Escherichia coli be in it is quick, in it is dense
Degree antibacterial circle diameter is 15.5mm, is Gao Min；High and low two concentration of medical fluid is in muting sensitive to salmonella, and middle concentration inhibition zone is straight
Diameter is 11.0mm, be in it is quick.Test result shows that various concentration medical fluid is sensitive to this 3 kinds of type strains, especially with the suppression of middle concentration
Bacterium effect is best, and fungistatic effect prompts Huangshi to dissipate by being followed successively by staphylococcus aureus, Escherichia coli, salmonella to weak by force
The fungistatic effect of aerosol G+ bacterium may be better than the fungistatic effect to G- bacterium.
As shown in Table 13, the scattered aerosol medical fluid of Huangshi of the present invention is best to the fungistatic effect of staphylococcus aureus, and MIC is
7.81mg/mL, the MIC to Escherichia coli, salmonella are respectively 31.25,250mg/mL.
Claims (5)
1. a kind of aerosol, it is characterised in that：It is made of the supplementary material of following weight proportion：
5 ~ 20 parts of bulk pharmaceutical chemicals, 10 ~ 100 parts of HFC-134a, 5 ~ 50 parts of isopropyl myristate, fumed silica 0.1 ~ 10
Part；
Wherein, the bulk pharmaceutical chemicals are following compositions 1 or composition 2：
Composition 1：10 parts of rheum officinale, 10 parts of the coptis, 10 parts of Cortex Phellodendri, 5 parts of Resina Draconis, 25 parts of calcined and quenched CALAMINA, 25 parts of calcined gypsum, alum
2.5 parts, 1 part of Pulvis Fellis Suis；
Composition 2：6 parts of pearl, 9 parts of elephant hide, 9 parts of amber, 9 parts of keel, 9 parts of calomel mercurous chloride, 1.8 parts of borneol, forges sweet stone at 3 parts of cow-bezoar
18 parts.
2. aerosol according to claim 1, it is characterised in that：It is made of the supplementary material of following weight proportion：
10 parts of bulk pharmaceutical chemicals, HFC-134a50 parts, 20 parts of isopropyl myristate, 0.8 part of fumed silica.
3. the method for preparing aerosol described in claim 1, it is characterised in that：It includes the following steps：
A. the bulk pharmaceutical chemicals for taking prescription amount, beat powder or water or organic solvent extracts, and vacuum drying, dried object is pulverized, obtained
Bulk pharmaceutical chemicals Ultramicro-powder；
B. bulk pharmaceutical chemicals Ultramicro-powder is added in surfactant, and be uniformly mixed, added suspending agent and obtain mixture；
C. mixture is packed into aerosol container, and pours into propellant, aerosol is made.
4. preparation method according to claim 3, it is characterised in that：The partial size of bulk pharmaceutical chemicals Ultramicro-powder made from a step is small
In 100 μm, moisture content is less than 9%.
5. the drug of aerosol of any of claims 1 or 2 skin ulcer caused by preparation treatment burn and scald, bedsore, diabetes
In purposes.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5683677A (en) * | 1988-12-06 | 1997-11-04 | Riker Laboratories, Inc. | Medicinal aerosol formulations |
| CN101757374A (en) * | 2008-12-25 | 2010-06-30 | 朱小放 | Medicine for curing burns and scalds and preparation method thereof |
| CN102652763A (en) * | 2011-03-01 | 2012-09-05 | 上海交通大学医学院附属第三人民医院 | Traditional Chinese medicine preparation for treating burn and scald and preparation method thereof |
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2015
- 2015-07-21 CN CN201510432010.7A patent/CN104997731B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5683677A (en) * | 1988-12-06 | 1997-11-04 | Riker Laboratories, Inc. | Medicinal aerosol formulations |
| CN101757374A (en) * | 2008-12-25 | 2010-06-30 | 朱小放 | Medicine for curing burns and scalds and preparation method thereof |
| CN102652763A (en) * | 2011-03-01 | 2012-09-05 | 上海交通大学医学院附属第三人民医院 | Traditional Chinese medicine preparation for treating burn and scald and preparation method thereof |
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