CN1738598A - Liquid formations for electrohydrodymanic spraying containing polymer and suspended particles - Google Patents
Liquid formations for electrohydrodymanic spraying containing polymer and suspended particles Download PDFInfo
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Abstract
A method of providing a droplet spray, includes supplying a liquid polymer formulation within which substantially inert particulate material is suspended to an outlet and subjecting liquid issuing from the outlet to an electric field that causes the liquid to break up into droplets.
Description
The preparation that the present invention relates in electrohydrodynamic processing, use.
Fluid electrodynamics (EHD) processing is for example having detailed description among the British patent GB-A-1569707.In this processing method, all have the distribution spray of same size (the single distribution) or microdroplet mist cloud basically and make by being introduced into the electric field from outlet or nozzle effusive liquid.
Electrohydrodynamic processing has obtained extensive application.One of them example that utilizes single partition characteristic of droplet spray or mist cloud is the inhaler field.In this field, electrohydrodynamic processing can be controlled the size (for example, by controlling liquid flow velocity and/or applied voltage) of microgranule, in addition, in conjunction with single partition characteristic of spraying or mist cloud, can be more accurately with the specific part of droplet spray to respiratory system.A kind of example of form of nasal inhalers has been described among the patent application WO 00/35524.Other application of electrohydrodynamic processing are the topical application aspect medicine or wound wrapping, at patent application WO 98/03267 description are arranged.
On the one hand, the invention provides and a kind ofly control the mist cloud produced by electrohydrodynamic processing or the method for spray droplets characteristic by being controlled at the liquid preparation that uses in the electrohydrodynamic processing.
On the one hand, the invention provides a kind of preparation that uses in electrohydrodynamic processing, preparation wherein comprises a kind of liquid of the particulate material that contains polymer and float on a liquid.
On the other hand, the invention provides a kind of preparation that uses in electrohydrodynamic processing, liquid wherein comprises polymer, and except that any active component, particulate material is suspended in the liquid.
This liquid can be for example a kind of polymer melt or polymer solution.
On the other hand; the invention provides a kind of preparation that in electrohydrodynamic processing (EHD), uses; preparation wherein comprises a kind of liquid; this liquid contains a kind of solvent; ethanol for example; a kind of polymer and contain the particulate material that granule at least is essentially inert material, for example, sugar, starch and polymer beads.
Herein, term " is essentially inert raw material " and refers to a kind of raw material that does not form the preparation active component, just, owing to electrohydrodynamic processing certain effect is arranged in the use of mist cloud or spray droplets though these are essentially inert raw material, these effects are not the predictive role for preparation yet.Because prepared mist cloud or spray droplets are suction or local uses that is specifically designed to human body or animal body, so these inert basically raw materials should be biocompatible raw material.Herein, term " bio-compatible " refers to, when the microdroplet that will make from a kind of preparation that contains this inert raw material by electrohydrodynamic processing, sucks by way of expectations or during local the use, there is not unexpected obvious retroaction in this raw material.
On the one hand, the invention provides a kind of preparation that in electrohydrodynamic processing, uses, this preparation comprises a kind of liquid solution and particulate material that contains the polyvinylpyrrolidone in ethanol, and wherein particulate material floats on a liquid with the form of sugar, starch or polymer beads.
Now spirit of the present invention is described by embodiment, and with reference to the accompanying drawings, wherein:
Fig. 1 is in order to realize the schematic representation of apparatus of electrohydrodynamic processing;
Fig. 2 is stability and polymer concentration curve chart, and the variation of spray characteristics has been described when being incorporated into the particle raw material in the preparation;
Fig. 3 a, 3b and 3c are in Fig. 2 zone a, b and c, carry out observed spray characteristics photo during the electrohydrodynamic processing with a preparation that does not conform to the particle raw material;
Photo shown in Fig. 4 a, 4b and the 4c and Fig. 3 a, 3b and 3c are similar, are respectively the photo when having introduced the particle raw material in the preparation;
Fig. 5 a and 5b in order to explanation be, the bar diagram that the first inert particle raw material that suspends with different first polymer concentration in the preparation is influenced microdroplet expansion and Peak Flow Rate respectively;
Fig. 6 a and 6b and Fig. 5 a and 5b be similar bar diagram, is respectively the bar diagram when having introduced second kind of different polymer in the preparation;
Fig. 7 a and 7b and Fig. 6 a and 6b are similar bar diagram, are respectively, though also introduced identical polymer in this preparation, what illustrate is the bar diagram of the influence of second kind of different inert raw material of suspension in preparation;
Fig. 8 a and 8b and Fig. 5 a and 5b are similar bar diagram, are respectively, and introduce the bar diagram of the third different polymer to the influence of the second kind of inert particle raw material that suspend in this polymer in this preparation;
Fig. 9 a and 9b and Fig. 8 a and 8b are similar bar diagram, are respectively in preparation the bar diagram when introducing another kind of polymer;
Figure 10 a and 10b contain the spray characteristics photo of preparation of glycerol for explanation, and wherein Figure 10 a explanation is spray characteristics when not introducing particle, Figure 10 b explanation be the influence of introducing particle;
Figure 11 a and 11b contain the spray characteristics photo of preparation of ethyl cellulose for explanation, and wherein Figure 11 a explanation is spray characteristics when not introducing particle, Figure 10 b explanation be the influence of introducing particle; With
Figure 12 is the sketch (not comprising outer housing) in order to the distributor of distributing fluids electrodynamics process preparation.
Referring now to accompanying drawing, the sketch that Fig. 1 shows for the electrohydrodynamic processing device below will describing, used in the experiment.As shown in FIG. 1, the electrohydrodynamic processing device comprises a container 1, and by this container, the preparation that will carry out the electrohydrodynamic processing processing is pumped into by pump 2 and has in the metal capillary 3 that exports 3a.Metal capillary is connected on the high voltage power supply 4, and in an embodiment, this power supply can provide 7 kilovolts～8 kilovolts voltage.Outlet 3a is positioned on the grounding plate 5, and in the present embodiment, this metallic plate is lower than 1.5 centimetres of outlet 3a.
As hereinafter describing, experiment will be carried out with the preparation that the different polymer in the solvent form that is dissolved in by variable concentrations, and all introduces and do not introduce the experiment of inert particle stock suspension.In order to eliminate the influence of flow velocity to static processing, the Control of Voltage that high voltage power supply 4 is provided is within a constant scope.Such as hereinafter description, will test with various different preparations for the microdroplet expansion of stablizing microdroplet formulations or argument α and Peak Flow Rate.By the expansion of the microdroplet on the microscope monitoring grounding plate 5, the preparation flow velocity 7.2 milliliters/hour (2 microlitre/seconds) gets off to measure argument α (this angle is the subtense α (supposition sedimentation pattern is circular substantially) that the sedimentation pattern of formation on the metallic plate 5 forms at nozzle 3a place).The spray characteristics photo uses a digital camera to take pictures.
Fig. 2 is an explanation adds polymer and suspension inert particle raw material in solvent or liquid mixture a influence curve, with regard to solvent itself, because its too high electric conductivity can not form a stable circular cone jet or a jet flow.
Fig. 2 represents that stability strengthens speed and polymer concentration strengthens the speed graph of relation, wherein curve X is the change curve that pulverability raises with the polymer concentration that does not contain particle raw material preparation, and curve Y is the change curve that pulverability raises with the polymer concentration that contains particle raw material preparation.Stability to the spraying of producing by electrohydrodynamic processing is carried out visual evaluation, and with the parameter in two microdroplet preparation process: argument α and Peak Flow Rate are measured.
Curve X among Fig. 2 shows that the fluid electrodynamics spray characteristics that does not contain the polymer formulations of particle raw material has 3 characteristic areas, regional A, B and C.In regional A, when polymer concentration was still very low, observed splashings were a unsettled conical jet.But when polymer concentration continued to increase, spraying became gradually and settles out.Fig. 3 a is the photo of declare area A spray characteristics.
In area B, along with the increase of polymer concentration, the stability of spraying has small variation.Fig. 3 b is the photo of declare area B spray characteristics.
In zone C, the further increase of polymer concentration has caused the rising of viscosity, and jet is cracked to be microdroplet thereby stoped, and then has formed the Continuous Flow of liquid.Fig. 3 c is the photo of declare area C spray characteristics.
Therefore, from the photo of curve X, Fig. 2 and Fig. 3 a～3c as can be seen, adding polymer in the liquid that can not spray usually can be so that this liquid becomes sprayable liquid, and still, the stability of electrohydrodynamic processing or spraying has very big dependency to the concentration of polymer.
Curve Y among Fig. 2 explanation be the influence of suspension inert particle raw material in the preparation, Fig. 4 a, 4b and 4c are the spray characteristics in regional A, B and the corresponding polymer concentration of C zone among observed and Fig. 2.From Fig. 2 and the photo among Fig. 4 a, 4b and the 4c as can be seen, in preparation, introduce of the stability significantly influence of particle raw material to the spraying of the fluid electrodynamics in the area B.But, the introducing of particle raw material has but improved the stability of regional A and zone C significantly, makes that the stability of fluid electrodynamics spraying of preparation is not too responsive to the concentration of polymer in the preparation, thereby makes, if desired, can use the polymer of low concentration.In addition, when being suspended with particulate material in the preparation, argument α increases usually, especially in the preparation of those low copolymer concentrations.In each embodiment,, can obtain flow velocity suitable or that increase by adding the particle raw material.In addition, increase the content of particle raw material in the preparation, identical or bigger increase has taken place with maximum obtainable flow rate in the argument α of stable spraying.
Now, to describing in detail by the various experiments of deriving from Fig. 2 curve.
In the present embodiment, preparation is by being dissolved in the ethanol, and molecular weight is that 40000 (PVP 40K) polyvinylpyrrolidone is formed, and is divided into adding inert particle raw material sugar and not adding two kinds of situations of inert particle raw material sugar.During experiment, the scope of polymer concentration is that every milliliter of ethanol contains 40 milligrams of PVP 40K (that is to say, add 40 milligrams of PVP 40K) and contains maximum 520 milligrams of PVP 40K:1 to every milliliter of ethanol in every milliliter of ethanol) do not contain any inert particle raw material; 2) contain the sugar (every milliliter of ethanol contains 0.1 gram sugar) of low concentration; With 3) contain the sugar (every milliliter of ethanol contains 0.5 gram sugar) of relative high concentration.
Fig. 5 a is that as described above usefulness centimetre is the microdroplet expansion (the just diameter of droplet sedimentation pattern or mean breadth on the earth plate) measured of unit and the bar diagram that concerns of three kinds of polymer concentration situations, Fig. 5 b is the bar diagram that concerns with the Peak Flow Rate of milliliter/hour metering and three kinds of polymer concentration situations, voltage is reduced to 4.7 kv/cm, also promptly, the voltage that provides of high voltage power supply is approximately described in the embodiment above 7 kilovolts.Serving as reasons shown in the white post bar do not contain the resulting result of particulate material preparation, serving as reasons shown in the post bar of band vertical stripes contains the resulting result of relative low concentration inert particle raw material preparation, and serving as reasons shown in the post bar of band parallel stripes contains the resulting result of relative high concentration inert particle raw material preparation.
As can be seen, the concentration of PVP 40K is high more in the preparation from Fig. 5 a and 5b, and the sprayable performance of preparation is just high more.In addition, in every milliliter of ethanol in the preparation of content between 40 milligrams～180 milligrams of polymer suspension inert particle raw material can improve the pulverability of these preparations.(arrow among Fig. 5 b represents that for a granular preparation, its Peak Flow Rate does not drop in the test specification yet, that is to say that under 16 milliliters/hour situation, the gained spraying is still very stable, even to such an extent as under higher flow velocity, spraying still might keep stable.)
From Fig. 5 b as can be seen, maximum obtainable flow rate increases along with the increase of inert particle material concentration, wherein the content of maximum obtainable flow rate polymer in every milliliter of ethanol reaches maximum between 40 milligrams～180 milligrams increases, and it is corresponding with the regional A shown in Fig. 2.
When the content of polymer concentration polymer in every milliliter of ethanol is (corresponding to the area B among Fig. 2) between 180 milligrams～320 milligrams the time, add polymer separately and be enough to stable spraying, and the influence that the particle raw material adds is very unclear.When the content of polymer concentration polymer in every milliliter of ethanol is (corresponding to the zone C among Fig. 2) between 320 milligrams～560 milligrams the time, because the raising of viscosity is broken to thread (shown in Fig. 3 c) with jet, thereby the sprayable property of the preparation that does not contain the particle raw material is descended gradually.For these high viscosity formulation, by comparison diagram 3c and 4c as can be seen, the adding of solid particle raw material can recover effusive expansion, thereby making to spray by electrohydrodynamic processing becomes possibility.In higher range of viscosities, maximum obtainable flow rate is not subjected to the appreciable impact that particulate material adds.No matter whether (every milliliter of ethanol contains 520 milligrams of polymer and contains 560 milligrams of polymer to every milliliter of ethanol) add the solid particle raw material under the very high situation of polymer concentration, and jet all tends to the destroyed thread that is.
In the present embodiment, preparation forms by being dissolved in polyvinylpyrrolidone 360K in the ethanol that (just the molecular weight of polyvinylpyrrolidone is 360,000), divides and introduce particle raw material sugar and do not introduce two kinds of situations of particle raw material sugar, equally also divide high concentration and low concentration two kinds of situations.Bar diagram shown in Fig. 6 a and the 6b is similar with Fig. 5 a and 5b respectively, in order to illustrate when the content of PVP 360K in every milliliter of ethanol is between 1 milligram～45 milligrams, the variation of microdroplet expansion and Peak Flow Rate, equally, serving as reasons shown in the white post bar do not contain the resulting result of particle raw material preparation, serving as reasons shown in the post bar of band vertical stripes contains low concentration sugar (every milliliter of ethanol contains 0.1 gram) the resulting result of preparation, and serving as reasons shown in the post bar of band parallel stripes contains relative high concentration sugar (every milliliter of ethanol contains 0.5 gram) the resulting result of preparation.Equally, in the microdroplet shown in Fig. 6 a expansion measurement of rate of flow, and be to carry out under the condition of 4.7 kv/cm at the obtained Peak Flow Rate shown in Fig. 6 a in field intensity with 7.2 milliliters/hour.
From Fig. 6 a to 7b as can be seen, contain 2 milligram hours (corresponding to the regional A among Fig. 2) when polymer concentration is increased to every milliliter of ethanol, the electrohydrodynamic processing characteristic of preparation improves along with the adding of particle raw material (sugar or starch).When polymer concentration is that every milliliter of ethanol contains 4 milligrams to every milliliter ethanol and contains 6 milligram hours (corresponding to the area B among Fig. 2), can obtain stable spraying.When polymer concentration is every milliliter of ethanol when containing more than 6 milligrams (corresponding to the zone C among Fig. 2), the spraying that does not contain particle raw material preparation is destroyed rapidly.The maximum increase of the Peak Flow Rate that can obtain by introducing the particle raw material occurs in (every milliliter of ethanol contains 10～45 milligrams) under the higher polymer concentration.By Fig. 6 a and 7b as can be seen, introduce the particle raw material and improved microdroplet expansion or argument significantly, simultaneously, existing in the whole polymer concentration scope of solid suspended particle all is useful.The upper content limit of polymer is 45 milligrams in every milliliter of ethanol, because under so high polymer concentration, no matter whether contains solid suspended particle in the preparation, all is fiber product but not microdroplet product with electrohydrodynamic processing obtained.
In the present embodiment, used polymer is low viscous ethyl cellulose preparation, and it is 80: 20 a toluene by being dissolved in volume ratio: the ethyl cellulose of 5 volume % in the alcohol mixture is formed, and under 25 ℃, its viscosity is 15 centipoises.The ethyl cellulose preparation of indication is herein
LoEthyl cellulose (
LoEC).Obtain four kinds of different polymer formulations in the following way, the ethyl cellulose preparation of two kinds of variable concentrations in the ethanol (every milliliter of ethanol contains 20 milligrams and every milliliter of ethanol and contains 100 milligrams) is 3: 7 ethanol by volume ratio: the preparation of two kinds of variable concentrations of the mixed solvent preparation that water is formed (every milliliter of mixed solvent contain 20 milligrams contain 100 milligram with every milliliter of mixed solvent).(ethanol or ethanol: water) preparation that is suspended with 0.5 gram starch granules raw material all experimentizes to every milliliter of solvent in the preparation that do not contain any particle raw material in each preparation and the preparation.Equally, be respectively microdroplet expansion and Peak Flow Rate shown in Fig. 8 a and the 8b, wherein the microdroplet expansion obtains under 7.2 milliliters/hour flow velocity, and maximum obtainable flow rate is then observed under field intensity is the condition of 4.7 kv/cm.In Fig. 8 a and 8b, shown in the white post bar is resulting result under the condition that does not contain suspension starch, and shown in the post bar of band parallel stripes then is the resulting result of starch-containing preparation.
From Fig. 8 a as can be seen, contain the low concentration polymer preparation of (every milliliter of solvent contains 20 milligrams), introduce the particle raw material and not only improved the microdroplet expansion significantly, also improved the Peak Flow Rate under these concentration simultaneously significantly for those.
Embodiment 5
In the present embodiment, employed polymer still is the ethyl cellulose preparation, in this case, be the high viscosity formulation of being made up of Ethocel (trade name) standard 100 high-quality ethyl celluloses (being provided by Dow Chemical), its viscosity under 25 ℃ is 100 centipoises.The polymer of indication is herein
HiEthyl cellulose (
HiEC).Solvent is an ethanol.Test two kinds of different polymer concentration preparations, first kind of polymer concentration is that every milliliter of ethanol contains 8 milligrams of polymer, and second kind of polymer concentration is that every milliliter of ethanol contains 40 milligrams of polymer.In addition, these two kinds of polymer formulations are all tested under the condition of introducing and do not introduce the suspension starch granules.When adding particle, granule density is that every milliliter of ethanol contains 0.5 gram.White post bar shown in Fig. 9 a and the 9b not resulting result of preparation of starch-containing particulate material that serves as reasons, the resulting result of preparation who then serves as reasons and contain the particle raw material shown in the post bar of band parallel stripes.
As can be seen, when adding solid in the low copolymer concentration preparation, maximum obtainable flow rate increases from Fig. 9 b, and, whether no matter adding the solid particle raw material, the maximum obtainable flow rate of high polymer concentration preparation is still bigger.
Shown in the table 1 for the result who contains and the different glycerin preparations of the inert particle of the politef that does not contain 1 micron diameter (in the table for " PTFE ") pearl or 30 microns beades (being " glass " in the table) form experimentize.
Table 1
| Prescription | Voltage (kilovolt) | Expansion (centimetre) | Sprayability (7.2ml/hr or 15ml/hr) |
| 100% glycerol | 6.3-8.0 | 0.5 | Thread |
| 100% glycerol-10% glass | 6.83-9.0 | 1 | Outside=solid; Inside=liquid |
| 90% glycerol-10% ethanol | ＞5.9 | 0.5 | Thread |
| 90% glycerol-10% ethanol-10% politef | 7.0-8.0 | 0.8 | Outside=solid; Inside=liquid |
| 80% glycerol-20% ethanol | ＞6.3 | 0.5 | |
| 80% glycerol-20% ethanol-10% politef | 6.0-8.0 | 1 | Outside=solid; Inside=liquid |
| 70% glycerol-30% ethanol | 5.0-8.5 | 0.5 | Thread |
| 70% glycerol-30% ethanol-10% politef | 5.3-9.7 | 0.6 | Outside=solid; Inside=liquid; Bigger expansion (1.1 centimetres of) @15ml/hr |
| 50% glycerol-50% ethanol | 6.0-9.0 | 0.7 | Outside=solid; Inside=liquid; Bigger expansion (1.2 centimetres of) @15ml/hr |
| 50% glycerol-50% ethanol-10% politef | 5.0-8.0 | 1.5 | Spraying is good; Bigger expansion (1.7 centimetres of) @15ml/hr |
Because the high viscosity characteristic of solution shown in the table 1, so clearly localized area A, B and C.Shown in the photo among table 1 and Figure 10 a, in the scope that continue to suspend is provided, threadization is all taken place in the glycerol and the ethanol of any ratio of being tested.But after the inert particle (glass or politef pearl) that adds about 10 volume %, the argument shown in the pulverability of preparation and Figure 10 b photo all is significantly improved and increases.In these cases, spraying is made up of the skin spraying of a trickle microdroplet and the bigger internal layer spraying that is difficult for mobile microdroplet, the result causes sedimentation pattern on the earth plate by outer layer scattering microdroplet (in the table 1, outside=solid) and the coalescent liquid regions of internal layer (in the table 1, inside=liquid) form, and this is because, for example, some particle aggregations reduce the horizontal mobilitys of granule and/or liquid high viscosity to be stoped due to individual particle moves freely.The ethanol content of larger proportion can make argument obtain bigger increase in the preparation, and this has supported second kind of theory.
Embodiment 7
Be to contain 80 milligrams of concentration containing 60 milligrams and every milliliter of ethanol with every milliliter of ethanol shown in the table 2
HiEthyl cellulose (
HiEC) influence of adding suspension inert particle raw material in the polymer formulations of Zu Chenging.In this case, being suspended in the concentration that inert particle raw material in the preparation contains 30 microns is the inertia bead that every milliliter of ethanol contains 0.1 gram.
Table 2
| Prescription | Voltage (kilovolt) | Expansion (centimetre) | Sprayability (7.2ml/hr or 15ml/hr) |
| hiEC (60mg)+ethanol (1ml) | 5.95 | 1.2 | Spraying is good |
| hiEC (60mg)+ethanol (1ml)+glass (0.1g) | 4.79-5 | 1.5 | Scattering is serious |
| hiEC (80mg)+ethanol (1ml) | 7.56 | 0.8 | Single moving jet |
| hiEC (80mg)+ethanol (1ml)+glass (0.1g) | 7.5 | 1.5 | Spraying is good |
As can be seen from Table 2, behind the introducing inert particle raw material, when polymer concentration in the preparation was low, argument increased in polymer formulations, and when polymer concentration was higher in the preparation, spraying is stable to be increased.
Contain 80 milligram hours for every ml of formulation shown in Figure 11 a and the 11b, do not contain and the spray characteristics that contains particle raw material preparation.From table 2 and Figure 11 a and 11b as can be seen, introduce particulate material and improved fluid electrodynamics pulverability.
It is pointed out that preparation that inert particle raw material as described above contains bead is generally the inhalant or local use of human body skin.But this fact of viewed influence (Peak Flow Rate of increase and the argument of increase) means that but these influences should almost observed in any biocompatible inert raw material that can be suspended in the preparation when using glass particle and polymeric beads.
Particulate material can suspend for the known proper method of those skilled in the art with any.For example, can in container, introduce machinery or other agitators that can keep suspending.Other possible methods have, can in preparation, add a viscosity intensifier, as glycerol, water solublity arabic gum or cellulosic polymer derivant, as hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC) or carboxymethyl cellulose (CMC) or hydroxyethyl-cellulose (HEC).The method that other keep to suspend, for example, Tadros writes, and there is description in Th.F science and technology publishing house in the 50th page～59 pages on the textbook of publishing in 1987 " solid-liquid distribution ".Other methods that can be used to keep suspending have polymeric surfactant, for example, and the ATLOX series polymer surfactant of in Uniqema technology journal 00-4, describing.
From top embodiment as can be seen, suspension inert particle raw material helps the electrohydrodynamic processing of preparation in polymer formulations, can under higher flow velocity, obtain stable spraying, and argument is increased, like this, when keeping specific range between outlet 3a and the sedimentation surface, the spraying that is produced just can cover more large-area target surface.
Shown in Figure 12 by can be used for realizing above the partial sectional view of allotter 200 of electrohydrodynamic processing of description preparation.As can be seen from Figure 12, allotter comprises the outer housing 20 of first chamber 21, chamber 21 comprises a power supply 22, as battery, and this power supply is connected on high tension generator 23 and the pump 24 by a switch SW, and pump 24 is connected on the liquid preparation container 25, the preparation in the container is pumped into has in the pipe that exports 30a (demonstration be partial sectional view).Pipe 30 extends to second chamber 26 that comprises the distribution outlet 20a of an outer housing from first chamber 21.In the present embodiment, pipe 30 is for electric insulation and have an electrode 31 that is coupled on the high-tension electricity outlet line 23a of high tension generator.Be supported on conductive core in the liquid outlet tube 30 or rod 32 by lead 22a ground connection or be connected on the cathode terminal of power supply 22.
After switch SW is opened, just can begin to operate this distributor, at this moment, between first electrode 31 and second electrode 32, form an electric field, liquid preparation is pumped into liquid outlet 30a by pump 24 from container 25.Then, the liquid of drawing from outlet 30a carries out fluid electrodynamics with liquid and pulverizes through just like high voltage electric field as described above, thereby produces microdroplet mist cloud or spraying, and is last, and these mist clouds or spraying are by distributing outlet 20a to draw from device.
As mentioned above, introduce the particle raw material and can obtain big flow velocity in preparation, like this, in the specific time, just can carry more strong dose agent, simultaneously, as described above, the argument of increase helps the spraying in the more intensive scope.
This distributor can be designed to form of nasal inhalers, in this case, preparation should contain one can be by the active component of nasal cavity conveying.Active component can be to be used for by to animal body, the medicament of handling as the mankind's treatment, operation or diagnosis, or improve human life quality's medicament.Medicament can also be antibiotic, anticancer preparation or other medical products, vaccine, protein, enzyme, DNA or dna segment or other biological product, anti-inflammatory preparation, vitamin, antibiotic preparation, morphine or other analgesics and nicotine etc.In addition, having in patent application WO 00/35524 can be in order to the description of the form of nasal inhalers distributor example that distributes above-mentioned preparation.
Equally, also distributor can be designed to be able to active component is applied topically to human body surface, as the device of skin surface or wound surface.In this case, the argument of increase can make and be applied topically on the bigger area.
The example that other can be used for distributing the distributor of preparation of the present invention has been described among the patent application WO 98/03267.
Also this distributor can be designed to be used for distributing active component is the mist cloud or the spraying of pesticide or other product for agriculture, equally, making device to be placed by the argument of introducing the increase that the particle raw material obtains more closely needs spraying face (for example, leaf surfaces) position, and can keep simultaneously the area coverage expected, like this, not only help and can guarantee the active component that mist cloud or droplet spray carry and to be deposited in desired destination thing surface.
The description of the example of other fluid electrodynamics reducing mechanisms that can be used for distributing preparation of the present invention is arranged in patent application WO 94/12285, WO 94/14543, WO 95/26235, WO00/35524, WO 99/07478 and WO 00/03267, and the content of all these patent applications all is hereby incorporated by.
Particulate material can be formed by any perhaps how dissimilar raw material, and unique what need restriction is that particulate material can bio-compatible and is insoluble to polymer formulations basically and can be suspended in the polymer formulations.The example of particulate material kind has: Chalk or kaolin particle or other are insoluble to the bio-compatible polymer beads of polymer formulations; Spice, this dosage form are to be used for orally, as artificial or natural sweetener (for example, simple sugars and glycoconjugates) and/or effervescent granule, that is to say, and this granule effervescent in mouth, and effervescent does not take place in polymer formulations; The active component granule.The granule of all these types can be solid, hollow or porous.Other operable grain types comprise: microcapsule (for example, can be formed by other bioavailable polymers that is insoluble to polymer formulations); It is inertia (that is to say, contain air, gas or inert fluid) or contains an active component or solid, granule, liquid or gel state component; Dissolved or be assigned the polymer beads of active component; The active component surface is insoluble to polymer formulations with one, carries out the granule of coating as the coating of other bioavailable polymer.According to the characteristic of required dosage form, can use the granule of any or multiple such type, granule wherein can be or introduce a kind of active component, can use one or more different active components.Granular size can be same size (single distribute) or in a scope, diameter can be less than 1mm (being assumed to sphere) usually, typically, diameter is between submicron to 100 micron.Granule may not one be decided to be sphere, and it can be, for example, and elliposoidal, granular, fragment shape or bar-shaped.
As other probability, a certain proportion of at least particle raw material contains active component.In preparation, introduce active component helps to send by electrohydrodynamic processing salt form as particle active component, because its nonpolar nature, usually these salt can't be sent by electrohydrodynamic processing, because if be dissolved in the preparation, the electric conductivity of gained solution can be too high.
In above-described embodiment, solvent for use is ethanol or ethanol-water mixture, also can use other solvent.Equally, also can use bioavailable polymer.In addition, polymer formulations may not be a solution, also can be polymer melt, and certainly, in this case, particulate material should remain solid, simultaneously in molten polymer, and itself not fusion.Particulate material can be designed as during use and degrades, dissolves or decomposes, for example, and after suction or topical application.In one embodiment, particulate material can contain biodegradable or decomposable polymer, and it remains solid in polymer formulations, but after process fluid electrodynamics is handled, for example, after suction or topical application, degraded or decomposition takes place.Particulate material is made the generation that hollow as discussed above helps this process.
The suspension active component not only can make active component not spray (because its aqueous conductive too high) in preparation, and can guarantee not have active component in the microdroplet below certain size (measuring by particle size).The preparation that this may be very beneficial for distributing from inhaler is because this can guarantee the form of active component with attached microdroplet can be brought in the respiratory system.
Because " viscosity " of polymer effect also can effectively particulate matter be positioned on the object surface equably according to preparation of the present invention, and this polymer helps sending the active component that comprises in the particle raw material.
In the concrete preparation of the present invention, add polymer and improved the viscosity of preparation, thereby prolonged the storage life of suspension.As described above, the increase of flow velocity at first is because secondly the adding of polymer is because the adding of particle raw material.From above as can be seen, adding polymer and particulate material in suspension makes some originally can not have sprayable property by the liquid that electrohydrodynamic processing is sprayed, and increased the argument or the sedimentation angle of microdroplet, thereby helped the spraying that viscous fluid obtains more intensive scope.The buffering effect of polymer can particulate material be suspended in the preparation with any traditional approach, and need not to carry out micronization, because can guarantee that conical jet can not destroyed by big relatively particle between spray phase.In addition, spray characteristics even can significantly not be subjected to the negative effect of suspension distribution inequality and solid malsegregation.
Claims (30)
1. method that droplet spray is provided, this method comprises makes liquid preparation be fed to an outlet, and will introduce the electric field from the effusive liquid in exit, it is microdroplet that this electric field makes liquid cracked, this method comprises a kind of polymer formulations as liquid preparation of supply, wherein is suspended with inert basically particulate material.
2. comprise a kind of polymer solution that is dissolved in the solvent according to the polymer formulations that the process of claim 1 wherein.
3. according to the method for claim 2, solvent wherein is selected from ethanol and ethanol-water mixture.
4. comprise a kind of polymer that is selected from polyvinylpyrrolidone and ethyl cellulose according to the polymer formulations that the process of claim 1 wherein.
5. to comprise molecular weight be 40000 or 360000 polyvinylpyrrolidone as polymer and ethanol as solvent according to the polymer formulations that the process of claim 1 wherein.
According to the polymer formulations that the process of claim 1 wherein comprise a kind of in ethanol or ethanol-water mixture low viscosity or the solution of high viscosity ethyl cellulose preparation.
7. 40mg～500mg the molecular weight that is included in 1 milliliter of ethanol according to the polymer formulations that the process of claim 1 wherein is 40000 polyvinylpyrrolidone, and contains 0.1 or 0.5 gram in per 1 milliliter of ethanol again and be suspended in particulate material in the preparation.
8. 40mg～180mg the molecular weight that is included in 1 milliliter of ethanol according to the polymer formulations that the process of claim 1 wherein is 40000 polyvinylpyrrolidone, and contains 0.1 or 0.5 gram in per 1 milliliter of ethanol again and be suspended in particulate material in the preparation.
9. 2mg～45mg the molecular weight that is included in 1 milliliter of ethanol according to the polymer formulations that the process of claim 1 wherein is 360000 polyvinylpyrrolidone, and contains 0.1 or 0.5 gram in per 1 milliliter of ethanol again and be suspended in particulate material in the preparation.
10. according to the method for arbitrary aforementioned claim, particulate material wherein comprises at least a sugar, starch and polymer beads.
11. according to the method for arbitrary aforementioned claim, particulate material wherein also comprises the granule of at least a active component or at least a active component.
12. according to the method for arbitrary aforementioned claim, polymer is wherein replaced by glycerol.
13. according to the method for arbitrary aforementioned claim, the particulate material that wherein inert basically particulate material is contained at least a active component replaces.
14. a liquid preparation that uses in the electrohydrodynamic processing device, said preparation comprises a kind of polymer formulations, and wherein inert basically particulate material is suspended.
15. according to the preparation of claim 14, liquid preparation wherein comprises a kind of polymer solution that is dissolved in the solvent.
16. according to the preparation of claim 15, solvent wherein is selected from ethanol and ethanol-water mixture.
17. according to the preparation of claim 14, liquid preparation wherein comprises a kind of polymer that is selected from polyvinylpyrrolidone and ethyl cellulose.
18. according to the preparation of claim 14, it is 40000 or 360000 polyvinylpyrrolidone as polymer and ethanol as solvent that liquid preparation wherein comprises molecular weight.
19. according to the preparation of claim 14, liquid preparation wherein comprises a kind of low viscosity or high viscosity ethyl cellulose solution in ethanol or ethanol-water mixture.
20. according to the preparation of claim 14,40mg～500mg molecular weight that liquid preparation wherein is included in 1 milliliter of ethanol is 40000 polyvinylpyrrolidone, and contains 0.1 or 0.5 gram in per 1 milliliter of ethanol again and be suspended in particulate material in the preparation.
21. according to the preparation of claim 14,40mg～180mg molecular weight that liquid preparation wherein is included in 1 milliliter of ethanol is 40000 polyvinylpyrrolidone, and contains 0.1 or 0.5 gram in per 1 milliliter of ethanol again and be suspended in particulate material in the preparation.
22. according to the preparation of claim 14,2mg～45mg molecular weight that liquid preparation wherein is included in 1 milliliter of ethanol is 360000 polyvinylpyrrolidone, and contains 0.1 or 0.5 gram in per 1 milliliter of ethanol again and be suspended in particulate material in the preparation.
23. according to the preparation of arbitrary aforementioned claim 14～22, particulate material wherein comprises at least a sugar, starch and polymer beads.
24. according to the preparation of arbitrary aforementioned claim 14～23, particulate material wherein also comprises the granule of at least a active component or at least a active component.
25. according to the preparation of arbitrary aforementioned claim 14～24, polymer is wherein replaced by glycerol.
26. according to the preparation of arbitrary aforementioned claim 14～25, the particulate material that wherein inert basically particulate material is contained at least a active component replaces.
27. a distributor, comprise that one has the outer housing that distributes outlet and contains: one is equipped with the liquid preparation container according to the liquid preparation of arbitrary claim 14～26; Be attached thereto to receive liquid from container and to have and distribute the liquid supply that exports adjacent liquid outlet; With one be used to provide the voltage source of processing by the voltage of the effusive liquid of liquid outlet, this voltage should be enough to be microdroplet with the liquid of drawing from outlet is cracked that microdroplet is by distributing outlet to draw outer housing.
28. according to the distributor of claim 27, voltage source wherein has the exercisable switch of a user.
29. according to the distributor of claim 27 or 28, wherein liquid supply includes a pump.
30. an inhaler comprises one and has the outer housing that the distribution outlet of droplet spray can be provided to nasal cavity, this outer housing comprises: one is equipped with the liquid preparation container according to the liquid preparation of arbitrary claim 14～26; Be attached thereto to receive liquid from container and to have and distribute the liquid supply that exports adjacent liquid outlet; With one be used to provide the voltage source of processing by the voltage of the effusive liquid of liquid outlet, this voltage should be enough to be microdroplet with the liquid of drawing from outlet is cracked that microdroplet is by distributing outlet to draw outer housing.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0107226.3 | 2001-03-22 | ||
| GBGB0107226.3A GB0107226D0 (en) | 2001-03-22 | 2001-03-22 | Formulations |
| GB0123646.2 | 2001-10-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1738598A true CN1738598A (en) | 2006-02-22 |
Family
ID=9911349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA028104781A Pending CN1738598A (en) | 2001-03-22 | 2002-03-22 | Liquid formations for electrohydrodymanic spraying containing polymer and suspended particles |
Country Status (5)
| Country | Link |
|---|---|
| KR (1) | KR20030096285A (en) |
| CN (1) | CN1738598A (en) |
| AT (1) | ATE413859T1 (en) |
| DE (1) | DE60229837D1 (en) |
| GB (2) | GB0107226D0 (en) |
-
2001
- 2001-03-22 GB GBGB0107226.3A patent/GB0107226D0/en not_active Ceased
- 2001-10-02 GB GBGB0123646.2A patent/GB0123646D0/en not_active Ceased
-
2002
- 2002-03-22 CN CNA028104781A patent/CN1738598A/en active Pending
- 2002-03-22 DE DE60229837T patent/DE60229837D1/en not_active Expired - Lifetime
- 2002-03-22 AT AT02713045T patent/ATE413859T1/en not_active IP Right Cessation
- 2002-03-22 KR KR10-2003-7012359A patent/KR20030096285A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| GB0107226D0 (en) | 2001-05-16 |
| GB0123646D0 (en) | 2001-11-21 |
| ATE413859T1 (en) | 2008-11-15 |
| DE60229837D1 (en) | 2008-12-24 |
| KR20030096285A (en) | 2003-12-24 |
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