WO2012177031A1

WO2012177031A1 - Method for manufacturing bubbles for promoting the transfer of a functional material, and functional-material transfer device using same

Info

Publication number: WO2012177031A1
Application number: PCT/KR2012/004839
Authority: WO
Inventors: 서종우; 김기두
Original assignee: 주식회사 퍼시픽시스템
Priority date: 2011-06-21
Filing date: 2012-06-19
Publication date: 2012-12-27
Also published as: KR20120140290A

Abstract

The present invention relates to a method for manufacturing bubbles for promoting the transfer of a functional material, and to a functional-material transfer device using same. The functional-material transfer device comprises: a main body; and a probe. The main body outputs an ultrasonic wave oscillation having a wavelength linked to the size of a bubble which is mixed with the functional material and transferred, as a mixture, into an object. The probe is connected to the main body so as to enable the ultrasonic wave oscillation to contact the object coated with the mixture, thereby applying the ultrasonic wave oscillation to the object. The ultrasonic wave oscillation having the wavelength linked to the size of the bubble may generate a hollowing phenomenon in the bubble applied to the object.

Description

Bubble manufacturing method for facilitating delivery of functional material and functional material delivery device using same

The present invention relates to a cosmetic field using ultrasonic waves, and more particularly, to a bubble manufacturing method for promoting the delivery of a functional material and a functional material delivery device using the same.

In general, the skin of the human body protects itself from external stimuli and substances in the barrier zone. In other words, water-soluble substances are difficult to enter the skin. Therefore, no matter how much cosmetics with effective ingredients can achieve satisfactory results for skin improvement. Therefore, in order to penetrate such substances into the skin, conventionally, absorption accelerators or transdermal penetration of macromolecular drugs have been used. On the other hand, mass transfer through the skin was done with the help of a professional masseuse, using an absorption accelerator or a skin stimulator such as an iontopresence device, to a skin care store or physical therapy room. However, this method has a problem of efficiency of mass transfer despite the extra time and expensive expenses.

One object of the present invention for solving the above problems is to provide a method for producing a bubble that can facilitate the delivery of the functional material to the subject.

An object of the present invention to provide a functional material delivery device using the bubble.

According to one embodiment of the present invention for achieving the above object, a method for preparing bubbles for facilitating delivery of a functional material comprises the steps of: providing a first mixture comprising a proportion of shell material; Mixing the first mixture and the core material to provide a second mixture; Filtering the second mixture to provide bubbles having a radius of 3 to 450 um; And separating the air bubbles having a size of 3 to 450 um by size.

In an embodiment, the shell material may be albumin.

The core material is liquefied perfluorobutane, and providing the first mixture comprises diluting an amount of albumin in a first volume of saline; Extracting a second volume of the mixture from the diluted mixture; And cooling the second volume of mixture below a certain temperature to provide the first mixture,

Providing the second mixture includes adding a third volume of liquefied perfluorobutane to the cooled mixture to provide the second mixture, wherein providing the bubbles comprises at least the second mixture. The filtering may include filtering using one thin film filter, and the separating the bubbles by size may classify the filtered second mixture by sizes using a centrifuge.

Providing the second mixture may be performed by mixing the mixture to which the liquefied perfluorobutane is added with a shaker having a predetermined number of revolutions per minute.

Providing the second mixture may be performed by applying ultrasonic waves to the mixture to which the liquefied perfluorobutane is added.

In some embodiments, the shell material may be lipid based.

Wherein the core material is liquefied perfluorobutane and the providing of the first mixture comprises diluting a first volume of glycerol and a second volume of propylene glycol in a third volume of saline; Adding a first weight of DPPC powder and a second weight of DPPA powder to the diluted mixture; Dissolving the powder by heating the mixture to which the powder is added at a constant temperature range; Extracting a fourth volume of the mixture from the additive in which the powder is dissolved; And cooling the fourth volume of mixture below a certain temperature to provide the first mixture, wherein providing the second mixture comprises adding a fifth volume of liquefied perfluorobutane to the cooled mixture. And providing the second mixture, wherein providing the bubbles includes filtering the second mixture using at least one thin film filter, and separating the bubbles by size comprises: The filtered second mixture can be sorted by size using a centrifuge.

In an embodiment, the shell material may be a phospholipid.

The core material is liquefied perfluorobutane and the step of providing the first mixture comprises dissolving a first weight of DPPC powder in a first volume of chloroform; Placing the dissolved solution in a container and evaporating in a vacuum chamber; Adding a saline buffered with a second volume of ginseng salt to the vesicle formed on the surface of the container; Extracting a third volume of the mixture from the salt added material; And cooling the third volume of mixture below a certain temperature to provide the first mixture, wherein providing the second mixture comprises adding a fourth volume of liquefied perfluorobutane to the cooled mixture. To seal; Heating the closed mixture to 46 ° C. to phase convert it into a monolayer; And mixing the phase-converted material by mixing with a shaker having a predetermined number of revolutions per minute to provide the second mixture.

Providing the bubbles may include filtering the second mixture using at least one thin film filter, and separating the bubbles by size may include separating the filtered second mixture by sizes using a centrifuge. Can be classified.

Functional material delivery apparatus according to an embodiment of the present invention for achieving the above object includes a body portion and a pro portion. The body portion outputs an ultrasonic oscillation having a wavelength that is mixed with a functional material and interlocks with the size of bubbles delivered to the object as a mixture. The pro part is connected to the main body part and applies the ultrasonic wave oscillation transmitted from the main body part to the object to which the mixture is applied to the object. Ultrasonic oscillation having a wavelength associated with the size of the bubble generates a cavitation phenomenon in the bubble applied to the object.

In an embodiment, the bubble may have a radius of 3 ~ 450um.

In an embodiment, the mixture may include the functional material, the bubble and distilled water.

In an embodiment, the functional material may be any one of vitamin C, vitamin A, anti-wrinkle agent, whitening agent, depilatory agent and anti-hair loss agent.

In example embodiments, the main body may include an input unit configured to set the wavelength of the ultrasonic wave such that the wavelength of the ultrasonic wave has a wavelength that is linked to the size of the bubble.

According to the embodiments of the present invention as described above, it is possible to manufacture a bubble for promoting the delivery of the functional material to the desired size and to increase the absorption rate of the functional material delivered to the object.

1 is a block diagram showing a functional material delivery device according to an embodiment of the present invention.

2 is a block diagram showing a configuration of the main body of FIG. 1 according to an embodiment of the present invention.

3 shows an example of the probe of FIG. 1 in accordance with an embodiment of the present invention.

4 illustrates an example of the probe of FIG. 1 in accordance with another embodiment of the present invention.

5 shows a functional mass transfer system according to one embodiment of the invention.

6 is a view showing the medium of FIG. 5 in more detail.

FIG. 7 schematically illustrates a relationship between a probe, a medium, and an object in FIG. 6.

8 is a flowchart illustrating a functional material delivery method according to an embodiment of the present invention.

9 is a flowchart illustrating a functional material delivery method according to another embodiment of the present invention.

FIG. 10 is a flow chart showing in detail the steps of manufacturing the bubble in FIG.

FIG. 11 shows the results of applying the functional mass transfer system of FIG. 5 to a rat according to an embodiment of the present invention. FIG.

FIG. 12 shows an increase rate in the case of using a lipid bubble in the embodiment of FIG.

FIG. 13 shows the results of applying the functional mass transfer system of FIG. 5 to mice according to molecular weight. FIG.

FIG. 14 shows an increase rate when using protein bubbles in the example of FIG. 13.

15 and 16 show shell characteristics according to the material constituting the bubble. [0029] FIG. 17 is a flow chart illustrating a method for producing a bubble for facilitating delivery of a functional material according to an embodiment of the present invention.

18 is a flowchart illustrating the bubble manufacturing method of FIG. 17 according to an embodiment of the present invention in more detail.

19 is a flow chart illustrating in more detail the bubble manufacturing method of FIG. 17 according to another embodiment of the present invention.

20 is a flow chart illustrating in more detail the bubble manufacturing method of FIG. 17 according to another embodiment of the present invention.

FIG. 21 is a flowchart illustrating the bubble manufacturing method of FIG. 17 according to another embodiment of the present invention in more detail.

With respect to the embodiments of the present invention disclosed in the text, specific structural to functional descriptions are merely illustrated for the purpose of describing embodiments of the present invention, embodiments of the present invention may be implemented in various forms and It should not be construed as limited to the embodiments described in.

As the inventive concept allows for various changes and numerous modifications, particular embodiments will be illustrated in the drawings and described in detail in the text. However, this is not intended to limit the present invention to a specific disclosed form, it should be understood to include all modifications, equivalents, and substitutes included in the spirit and scope of the present invention.

Terms such as first and second may be used to describe various components, but the components should not be limited by the terms. The terms may be used for the purpose of distinguishing one component from another component. For example, without departing from the scope of the present invention, the first component may be referred to as the second component, and similarly, the second component may also be referred to as the first component.

When a component is referred to as being "connected" or "connected" to another component, it may be directly connected to or connected to that other component, but it may be understood that other components may be present in between. Should be. On the other hand, when a component is said to be "directly connected" or "directly connected" to another component, it should be understood that there is no other component in between. Other expressions describing the relationship between components, such as "between" and "immediately between," or "neighboring to," and "directly neighboring to" should be interpreted as well.

The terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting of the present invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this application, the terms "comprise" or "having" are intended to indicate that there is a feature, number, step, action, component, part, or combination thereof that is described, and that one or more other features or numbers are present. It should be understood that it does not exclude in advance the possibility of the presence or addition of steps, actions, components, parts or combinations thereof.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art. Terms such as those defined in the commonly used dictionaries should be construed as meanings consistent with the meanings in the context of the related art and shall not be construed in ideal or excessively formal meanings unless expressly defined in this application. .

Hereinafter, with reference to the accompanying drawings, it will be described in detail a preferred embodiment of the present invention. The same reference numerals are used for the same elements in the drawings, and duplicate descriptions of the same elements are omitted.

Referring to FIG. 1, the functional material delivery device 10 according to an embodiment of the present invention includes a main body part 100 and a pro part 200. The main body 100 and the pro part 200 are connected by a cable 30. The pro part 200 includes a housing 220 in which the ultrasonic oscillator 210 and the ultrasonic oscillator 210 are accommodated. Although not shown, the functional material delivery device 10 may be connected to a computer or the like with a data communication cable to perform data communication with each other.

The main body 100 is mixed with a functional material and outputs an ultrasonic wave having a wavelength that is linked to the size of bubbles delivered to the object (for example, the skin) as a mixture. The pro part 200 applies the ultrasonic rash transmitted from the main body part 100 to the object in contact with the object (for example, the skin) to which the mixture is applied. As described below with reference to FIGS. 15 and 16, the bubble may vary in intensity depending on its size, and thus, the ultrasound delivered to the object may have a wavelength that is linked to the size of the bubble.

Referring to FIG. 2, the main body unit 100 includes a power conversion unit 110, a control unit 120, a power amplification unit 150, and an input unit 160. The controller 120 includes a power controller 130 and a main controller 140. The main body 100 may further include a display unit 170 and an auxiliary power supply 180.

The power converter 110 is connected to a commercial AC voltage ACV under the control of the power controller 130 and converts the AC voltage ACV into a pulse-shaped square wave PSW. The power converter 110 may be implemented as an asymmetric half bridge circuit to convert an AC voltage ACV into an asymmetric pulse-shaped square wave PSW. Here, asymmetry means that the maximum voltage and the minimum voltage of the pulse-shaped square wave PSW are not equal.

The power amplifier 150 is connected to the power converter 110 and receives the pulse-shaped square wave PSW from the power converter 110 under the control of the main controller 140. Amplifies and outputs the ultrasonic wave oscillator 210 of the probe 200 through the cable 40. The ultrasonic oscillator 210 may contact the skin on which the functional material and the bubble are applied. At this time, the ultrasonic wave applied to the skin from the ultrasonic wave oscillator 210 may have a wavelength that is linked to the size of the bubble. The wavelength and the duty ratio of the ultrasonic wave may be set by an input signal INPUT received through the input unit 160 and transmitted to the controller 120 through the input unit 160.

The ultrasonic oscillator 210 may be a single focus piezoelectric element, i.e., a transducer.

When mechanical pressure is applied to certain materials (solids), electrical polarization occurs. These materials are called piezo electrics, and these phenomena are called piezoelectric phenomena. Giving the appearance changes the shape.

Representative piezoelectric materials used in piezoelectric elements include quartz, rosell salt, barium titanate, and the like, and have recently been replaced by artificial ceramics such as PZT. Applying an alternating voltage to both sides of the piezoelectric material causes expansion and contraction depending on the polarity of the current, which is repeated in proportion to the frequency of the alternating voltage.

In particular, the piezoelectric material is composed of a large number of dipoles, and these dipoles have piezoelectric properties only when they are maintained in a geometrical arrangement. The piezoelectric material has a resonant frequency for converting electrical energy into acoustic energy most efficiently. The resonant frequency is determined according to the thickness of the piezoelectric material. The thickness of the piezoelectric material determines the natural frequency of the device.

The controller 120 includes a main controller 140 and a power controller 130. The main controller 140 controls the power controller 130 and the power amplifier 150 according to the input signal INPUT received through the input unit 160 so that the ultrasonic wave having the wavelength and duty ratio according to the input signal is ultrasonic. Output from the driver 40 to the ultrasonic oscillator 210. The power controller 120 controls the power converter 110 according to the control of the main controller 140 so that the pulse-shaped square wave PSW has a frequency corresponding to the input signal and is output to the power amplifier 150. Be sure to

The input unit 160 receives an input signal INPUT. The wavelength, pulse repetition frequency, duty ratio, and application time of the ultrasonic wave provided from the power amplifier 150 to the probe 200 are determined by the input signal INPUT applied to the input unit 160. The input unit 160 transmits such an input signal INPUT to the control unit 120, and the control unit 120 controls the power conversion unit 110 and the power amplification unit 150 to display the characteristics determined by the input signal INPUT. Ultrasonic waves are provided to the probe 200.

The display unit 170 displays an input signal INPUT input to the input unit 160 so that the user can check it. The auxiliary power supply 180 receives the AC voltage ACV, converts it, and provides the converted AC voltage to the controller 120.

When the pulse-shaped square wave PSW is transmitted to the ultrasonic driver 150 with a duty ratio and a wavelength according to the input signal INPUT, the power amplifier 150 amplifies the pulse-shaped square wave PSW to ultrasonic wave oscillator 210. Ultrasonic wave oscillator 210 which is transmitted to the skin and is in contact with the skin is irradiated with the ultrasonic wave transmitted from the power amplifier 150 to the object (skin) to which the mixture is applied. When ultrasonic waves are applied to the object (skin) to which the mixture is applied, the jet streaming and the micro streaming phenomenon occur well in the bubbles included in the mixture. When the bubble is streaming, the functional substances in the mixture are well absorbed into the skin. In the embodiment of the present invention, the wavelength of the ultrasonic wave transmitted from the ultrasonic wave oscillator 210 to the object is set to be linked to the size of the bubbles contained in the mixture. That is, the wavelength of the ultrasonic wave may have a constant distribution with respect to the size of the micro bubbles included in the mixture. In addition, as described below, the wavelength of the ultrasonic wave may be set in the input unit 160 to be linked to the size of the bubble manufactured according to the exemplary embodiment of the present invention. Therefore, the cavitation phenomenon that bubbles are grown and collapsed due to the micro air bubbles and ultrasonic energy of the bubbles react with each other with high probability, and the distribution thereof may be uniform. The mechanical energy generated in this process helps to transfer functional substances in the mixture to the dermis of the skin. In addition, the fine bubbles contained in the bubbles have a wavelength according to their average size. In an embodiment of the present invention, the wavelength of the ultrasonic wave may be set to be linked with the size of the bubble to increase energy efficiency. That is, the wavelength of the ultrasonic wave may be set to have a constant distribution (an integer multiple of the size of the air bubbles of the contrast agent) with respect to the size of the bubble. Therefore, it is possible to generate an ultrasonic wave having a wavelength that is linked to the size of the bubbles used to efficiently produce the cavitation phenomenon using low energy.

Referring to FIG. 3, the probe 200a includes a first connector 231 and a housing 240 connected to the first connector 231. Inside the housing 240, a second connector 232, a transducer 233, a piezoelectric element 235, and a transparent lens 236 are provided. A fluid layer 235 is interposed between the piezoelectric element 235 and the transparent lens 236. The probe 200a of FIG. 3 schematically illustrates an internal structure of the probe 200 of FIG. 1.

A cable 30 is connected to the first connector 231 and the second connector 232 to transmit a square wave from the ultrasonic driver 150. The square wave is transmitted to the piezoelectric element 234 through the second connector 232 and the transducer 233. The piezoelectric element 234 vibrates in response to the square wave to generate ultrasonic waves. The generated ultrasound is transmitted to the object (skin) through the fluid layer 235 and the transparent lens 236. The transparent lens 236 may be formed of TPX, EPOX, or the like, and the transparent lens 236 may be manufactured integrally with the housing 240. In addition, the surface of the transparent lens 236 may have a form in close contact with the object (skin).

Referring to FIG. 4, the probe 200b according to another embodiment of the present invention may include a connector 241 and a housing 260 connected to the connector 241. A cable (not shown) to which a light source is supplied may be connected to the connector 241. Inside the housing 260, an internal cable 242 for transmitting light, an isolator 243 for removing noise from the light, a wavelength division multiplexer 244 for selecting a wavelength of light output from the isolator 243, and a multiplexer 244. A focusing lens for converging a fiber amplifier 245 for amplifying the output of the amplifier, a coupler 246 for connecting the fiber amplifier 245 and the laser generator 247, and a laser 249 generated from the laser generator 247. 248 and the film 251 and the transparent lens 253 which generate ultrasonic waves in response to the focused laser from the condenser lens 248. The fluid layer 252 is disposed between the film 251 and the transparent lens 253. The focusing lens 248 causes focus on the surface of the film 251, and ultrasonic waves are generated in the film 251 in response to the generated focus. The film 251 may use polydimethylsiloxane (PDMS) having a high light absorption coefficient.

Referring to FIG. 5, the functional mass transfer system 300 includes a functional mass transfer device 305 and a medium 400. As described with reference to FIG. 1, the functional material delivery device 305 may include a main body 310 and a probe 330 connected to the main body 310 and a cable 320. The functional mass transfer device 305 is a medium having an ultrasonic wave having a wavelength (having a constant distribution) associated with the size of bubbles mixed with the functional substance included in the mixture applied to the medium 400 in contact with the object (skin). Or to the subject (skin) through the medium 400. The medium 400 may be a mask or a patch. When the medium 400 is a mask, the object may be facial skin, and when the medium 400 is a patch, the object may be skin or scalp. In FIG. 5, the medium 400 is implemented as a mask.

6 is a view showing the medium of FIG. 5 in more detail.

Referring to FIG. 6, when the portion 410 of the medium 400 is enlarged, it can be seen that the medium 400 is composed of a plurality of lattice structures 411. Each grating 411 is evenly coated with a mixture (or functional material). For example, when ultrasonic waves are applied after applying a mixture to an object (skin), most of the ultrasonic energy may be lost in the air layer when an air layer is placed between the probe surface and the object. However, when the medium 400 such as a mask or a patch is used as in the embodiment of the present invention, the mixture 412 containing the functional material is stably positioned in the lattice structure, thereby allowing the ultrasound energy to be well transmitted to the object.

Referring to FIG. 7, it can be seen that the medium 400 is positioned in contact with the object (skin) 460 and the probe 330 is in contact with the medium 400. Since the probe 330 may have the structure described with reference to FIGS. 3 to 4, ultrasound may be applied to the object 460 through the medium 400. Ultrasound applied from the probe 330 to the object 460 prevents a bioeffect that may occur due to the concentration of energy at one point, and evenly delivers energy to the target volume of the object 460 (the point where the probe 330 is located). It may be unfocused ultrasound. Alternatively, the ultrasound applied to the object 460 from the probe 330 may be focused ultrasound.

In embodiments of the present invention, the functional material delivered to the subject may be various. The functional substance may include vitamin C suitable for skin lightening agents and vitamin A which is widely used for anti-aging. In addition, hyaluronic acid is widely used as an anti-wrinkle agent because of its high bonding strength with the surrounding water molecules, such hyaluronic acid may be included in the functional material.

Functional material delivery system 300 according to an embodiment of the present invention can be applied not only to skin care but also to the field of wool and hair loss prevention. If the functional material contains a wool component and an anti-hair loss component, by placing the patch in a desired portion and irradiating the patch with the functional substance delivery device 305, the wool component and anti-hair loss component can be easily delivered into the scalp. have. Thus, the functional material may be a hair restorer whose main component is minoxidil. In addition, functional material delivery system 300 according to an embodiment of the present invention can be applied to the hair removal field. Thus, the functional substance may be a depilatory agent whose main ingredient is chioclicolic acid. In addition, the functional substance delivery system according to an embodiment of the present invention may be applied to the cosmetic field. Therefore, the functional substance may be a wrinkle improver or a whitening agent as a main component thereof.

Referring to Figure 8, in the functional material delivery method according to an embodiment of the present invention to generate a mixture by mixing the functional material and bubbles (S510). Here the functional material and the bubbles can be mixed in a constant proportion. The mixing ratio of the functional material and the bubble may be determined according to the sensitivity of the subject to the mixture. The mixture is applied to the target volume of the object (S520). Next, the ultrasonic wave having a wavelength interlocked with the size of the bubble is applied to the target volume using the functional substance delivery device 10 of FIG. 1 (S530).

Referring to Figure 9, in the functional material delivery method according to another embodiment of the present invention to prepare a bubble (S610). The mixing ratio of the functional material and the bubble may be determined according to the sensitivity of the subject to the mixture. The functional material and the prepared bubble are mixed to generate a mixture (S620). The medium is in close contact with the object (S630). Here, the subject may be skin and the medium may be a mask or a patch as shown in FIG. 5. The mixture is applied to the medium in close contact with the object (S640). Next, the ultrasonic wave having a wavelength that is interlocked with the size of the bubble is applied to the target volume of the medium using the functional substance delivery device 10 of FIG. 1 (S650).

Referring to FIG. 10, the first material having shell characteristics is diluted in saline (S611). The dilute first material is mixed with a second material having core properties to generate a shell-core mixture (S612). The shell-core mixture is filtered with a filter (S613). Filtration of the shell-core mixture with a filter can produce bubbles having the desired average size.

Bubbles consist of a gas core and a shell. The solubility is determined according to the characteristics of the gas core, and the hardness varies depending on the shell characteristics, and thus the degree of reaction to ultrasonic energy is different. Therefore, the bubble may be prepared by mixing a second material having a core property and a first material having a shell property at a predetermined ratio according to the purpose of use. As the first substance having shell properties used in the preparation of bubbles, albumin series and lipid series are mainly used. Lipid shells are both hard and flexible, and are slower to spread than albumin shells. A variety of materials may be used for the second material having core properties used for preparing the bubbles. For example, the second material may include various materials such as Air H, Octafluorpropane L, Decafluorobutane L, Nitrogen / perfluorohexane L, Sulfur hexafluoride L, Perfluorobutane L, Nitrogen H, Perfluoropropane L.

For example, when the albumin series is used as the first substance, the manufacturing process of bubbles is as follows.

a) Dilute 0.2 g of chilled bovine serum albumin in 50 ml of saline proportionally.

b) Extract 750 ul of diluted albumin

c) Properly mix 250ul of Perfluoropentane with diluted albumin.

d) Mix the mixture through VialMixer.

e) Filter by using Syringe Filter to extract bubbles with size suitable for the purpose.

For example, when the lipid series is used as the first substance, the manufacturing process of the bubbles is as follows.

a) Dilute 123ml of Glycerol proportionally with 27ml of saline solution.

b) Mix 150 ml of diluted Glycerol and 250 ml of Propylene Glycol.

c) Add 2.5 g of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 0.1 g of 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA) to the mixture.

d) The mixed material is heated at 60 ° C. for 30 minutes.

e) Extract 750ul of the heated material and mix 250ul of Perfluoropentane stored at room temperature.

f) Mix the mixture through VialMixer

g) Filter by using Syringe Filter to extract bubbles with the right size.

DPPC and DPPA can be frozen and stored in powder form. The heating time is heated until all powder is dissolved in the solution. The time can be adjusted according to the temperature. The manufacturing method of the above-described bubbles is one example, and the mixing ratio and mixing amount of each material may be changed in order to manufacture the shell characteristics and the core characteristics according to the intended use.

FIG. 11 shows the results of applying the functional mass transfer system of FIG. 5 to rats according to molecular weight.

In FIG. 11, lipid bubbles having a radius of 40 μm and ultrasonic waves having a wavelength of 7.5 mm were used.

Referring to FIG. 11, it can be seen that the contrast value of ultrasound + Dextran (with lipid bubbles) on the right is higher than that of ultrasound + Dextran (with US) at each molecular weight.

Referring to FIG. 12, it can be seen that the use of lipid bubbles in combination with ultrasound is significantly higher than in the case of only ultrasound.

FIG. 13 shows the results of applying the functional mass transfer system of FIG. 5 to rats according to molecular weight.

In FIG. 13, a protein bubble having a radius of 35 μm and an ultrasonic wave having a wavelength of 5.2 mm were used.

Referring to FIG. 13, it can be seen that the contrast value of ultrasound + Dextran (with protein bubbles) on the right is higher than that of ultrasound + Dextran (with US) at each molecular weight.

Referring to FIG. 14, it can be seen that the increase rate is considerably higher in the case of using the protein bubble with the ultrasonic waves than in the case of using only the ultrasonic waves.

15 and 16 show shell characteristics of bubbles according to the materials constituting the bubbles.

FIG. 15 shows bubble characteristics of bubbles according to strength when albumin series is used as a material having shell properties and Perfluorobutane is used as a material having core properties when preparing bubbles.

FIG. 16 shows bubble characteristics of bubbles according to strength when a lipid-based material is used as a material having a shell property and a perfluorobutane is used as a material having a core property when preparing bubbles.

Referring to FIGS. 15 and 16, it can be seen that the shell characteristics have a constant distribution when the albumin series is used or the lipid series is used as the material having the shell characteristics. Therefore, the ultrasonic wave according to the embodiment of the present invention may have a wavelength of interlocking bubbles. That is, the ultrasonic wave according to the embodiment of the present invention may have a wavelength within a constant distribution with respect to the size of the bubble.

According to the embodiments of the present invention, the ultrasonic bubbles and the functional material may be mixed and applied to an object (or a medium), and ultrasonic waves may be applied thereto to increase the probability of cavitation occurring, thereby increasing the absorption effect of the functional material.

17 is a flowchart illustrating a method for preparing bubbles for promoting delivery of a functional material according to one embodiment of the present invention.

Referring to FIG. 17, in the method for preparing bubbles for promoting delivery of a functional material, a first mixture including a predetermined ratio of shell material is provided (S700). Here, the shell material is a material that surrounds the surface of the bubble so that the bubble does not melt into the solution in order to ensure that the bubble is stably present for a long time in the solution containing the functional material. Examples of the material surrounding the bubble include albumin, lipids, phospholipids, polymers, and the like. Bubbles according to an embodiment of the present invention can be more free from the choice of shell material surrounding the bubbles because they are used in the skin, unlike conventional co-agents are used in the human body. The first mixture and the core material are mixed to provide a second mixture (S800). The core material is a gas inserted into the bubble to increase the stability of the bubble. In this way, the gas inserted into the bubble may be an inert gas which is less affected by a sudden change in temperature and pressure due to the movement of the bubble. Such inert gases include perfluorocarbon series. Filtering the second mixture provides a bubble having a radius of 3 ~ 450um size (S900). A thin film filter may be used for filtering the second mixture. Separate the bubbles having a radius of 3 ~ 450um size by size (S950). Centrifuge can be used to separate the bubbles having a radius of 3 ~ 450um by size.

18 shows a flowchart when albumin is used as the shell material. In the case of using albumin as a shell material, since albumin is water-soluble, albumin may be mixed in distilled water at a predetermined ratio, and then mixed with perfluorocarbon in a gas or liquefied state, and then foamed by external force. In this case, a high speed shaker or ultrasonic waves may be used to generate bubbles. Hereinafter, a method of preparing bubbles in the case where albumin is used will be described in more detail with reference to FIG. 18.

A certain amount of albumin is diluted in a first volume of saline solution (S711). The amount of albumin may be about 0.2 g, and the first volume of saline may be about 50 ml. The second volume of the mixture is extracted from the diluted solution (S712). Here, the second volume may be about 2 ml. A mixture of (S712) is extracted. The extracted mixture is cooled to below a predetermined temperature to provide a first mixture (S713). Wherein the constant temperature may be about 10 ℃ below zero. A third volume of liquefied perfluorobutan is added to the first mixture (S811). Here, the third volume may be about 100 ul. The mixture to which perfluorobutane is added is rotated with a shaker having a rotational speed per minute or more to provide a second mixture (S812). Here, the number of times may be about 4000 times. The second mixture is filtered using at least one thin film filter (S911). In step S911, the second mixture is first filtered using a first thin film filter having a pore size of 900 μm, and then the second mixture first filtered using a second thin film filter having a pore size of 6 μm. Can be filtered second. After two filtering, bubbles with a size of 3 ~ 450um can be obtained. Bubbles having a radius of 3 ~ 450um size are classified by size using a centrifuge (S951). Bubbles of a certain size are collected and stored from bubbles classified by size, and perfluorobutane can be added to a container containing bubbles classified by size to ensure bubble stability.

It is noted that the amount of material presented in each step of FIG. 18 is a relative amount, not an absolute amount.

19 shows a flow diagram when a lipid family is used as the shell material. In the case of using a lipid series as a shell material, since the lipid is not water soluble, heat is applied to the lipid. Glycerol DPPC, DPPA, etc. are mixed in a certain weight ratio in order to allow lipids to act on water, and then put in distilled or saline solution and heat. Next, after the solution is cooled down, liquefied perfluorocarbon may be mixed, and external force may be applied to generate bubbles. In this case, a high speed shaker or ultrasonic waves may be used to generate bubbles. Hereinafter, referring to FIG. 19, a method of preparing bubbles when lipids are used will be described in more detail.

The first volume of glycerol and the first two volumes of propylene-glycol are diluted in a third volume of saline (S721). Wherein the first volume may be about 2.5 ml, the second volume may be about 52.5 ml, and the third volume may be about 50 ml. In addition, the volume ratio of glycerol, propylene-glycol and saline may be 1:21:20. To the diluted mixture, a first weight of DPPC (1,2-Dipalmitoyl-sn-glycero-3-phosphocholine) and a second weight of DPPA (1,2-Dipalmitoyl-sn-glycero-3-phosphate Monosodium Salt) powder are added (S722). Here, both the first weight and the second weight may be about 0.1 g. The mixture to which the powder is added is heated in a certain temperature range to dissolve the powder (S723). The constant temperature range may be 60 ° C ~ 70 ° C. The mixture of the fourth volume is extracted from the additive in which the powder is dissolved (S724). Wherein the fourth volume may be about 2 ml. That is, the ratio of the third volume and the fourth volume may be 25: 1. The mixture of the fourth volume is cooled to below a predetermined temperature to provide a first mixture (S725). Wherein the constant temperature may be about 10 ℃ below zero. A fifth volume of liquefied perfluorobutane is added to the first mixture (S821). Here, the fifth volume may be about 10 ul. The mixture to which liquefied perfluorobutane is added is rotated with a shaker having a rotational speed per minute more than a predetermined number of revolutions per minute to provide a second mixture (S822). Here, the number of times may be about 4000 times. The second mixture is filtered using at least one thin film filter (S921). In the second step S921, the second mixture is first filtered using a first thin film filter having a pore size of 900 μm, and then filtered first using a second thin film filter having a pore size of 6 μm. 2 The mixture can be filtered second. After two filtering, bubbles with a size of 3 ~ 450um can be obtained. Bubbles having a radius of 3 ~ 450um size are classified by size using a centrifuge (S961). Bubbles of a certain size are collected and stored from bubbles classified by size, and perfluorobutane can be added to a container containing bubbles classified by size to ensure bubble stability.

Note that the amount of material presented in each step of FIG. 19 is a relative amount, not an absolute amount. That is, the material presented in each step may represent a ratio of relative amounts shown in the description of FIG. 19.

20 shows a flow diagram when a Phosphorlipid family is used as the shell material. In the case of using a phospholipid family as the shell material, the phospholipid has a polarity and is divided into a hydrophobic portion because of its polarity as opposed to a hydrophilic portion. Thus, when phospholipids are mixed with liquids such as polar water, they form a thin film on the water. Shaking such a mixture or applying force by applying an ultrasonic wave from the outside to form a bubble, the bubble may have a monolayer consisting of a hydrophilic exterior and a hydrophilic interior. Hereinafter, with reference to FIG. 20, a bubble manufacturing method in the case where phospholipid is used will be described in more detail.

The first weight of DPPC powder is dissolved in a first volume of chloroform (S731). Wherein the first weight may be 0.001g, the first volume may be 1ml. The solution is put in a container and evaporated in a vacuum chamber (S732). A second volume of PBS (phosphate buffered saline) is added to the vesicles thinly formed on the surface of the container (S733). Here, the second volume may be 100 ml. A third volume of the mixture is extracted from the PBS-added material (S734). Wherein the third volume may be 2 ml. The mixture of the third volume is cooled to below a predetermined temperature to provide a first mixture (S735). Wherein the constant temperature may be about 10 ℃ below zero. The fourth mixture is sealed by adding a fourth volume of perfluorobutane (S831). Wherein the fourth volume may be 10ul. The sealed mixture is heated to a predetermined temperature to be phase-converted to a monolayer (S832). Here, the constant temperature may be about 46 ° C. That is, the constant temperature here is a temperature at which the sealed mixture can cause phase conversion into a monolayer. The phase-converted material is rotated with a shaker having a rotation rate per minute or more to provide a second mixture (S833). Here, the number of times may be about 4000 times. The second mixture is filtered using at least one thin film filter (S931). In step S931, the second mixture is first filtered using a first thin film filter having a pore size of 900 μm, and then the second mixture is first filtered using a second thin film filter having a pore size of 6 μm. Can be filtered second. After two filtering, bubbles with a size of 3 ~ 450um can be obtained. Bubbles having a radius of 3 ~ 450um size are classified by size using a centrifuge (S971). Bubbles of a certain size are collected and stored from bubbles classified by size, and perfluorobutane can be added to a container containing bubbles classified by size to ensure bubble stability.

Note that the amounts of materials presented in each step of FIG. 20 are relative and not absolute. That is, the material presented in each step may represent a ratio of relative amounts shown in the description of FIG. 21.

Figure 21 shows a flow diagram when a polymer is used as the shell material. In the case of using a polymer as a shell material, polyelectrolytes having negative and positive polarities are alternately coated on phospholipid bubbles. After the bubbles have electrical properties, they are alternately coated with biocompatible polymers on the bubbles. Such biocompatible polymers include chitosan, algnate, and N-isopropylacrylamid. Afterwards, perfluorocarbon gas is added to the inner core to convert bubbles. Hereinafter, with reference to FIG. 21, a bubble manufacturing method in the case where a polymer is used will be described in more detail.

The first weight of DPPC powder is dissolved in the first volume of chloroform (S741). Wherein the first weight may be 0.001g, the first volume may be 1ml. The solution is put in a container and evaporated in a vacuum chamber (S742). A second volume of PBS (phosphate buffered saline) is added to the vesicles thinly formed on the surface of the container (S743). Here, the second volume may be 100 ml. The third volume of the mixture is extracted from the PBS-added material and mixed in a shaker having a predetermined number of revolutions per minute (S744). Wherein the third volume may be 2 ml and the predetermined number of times may be about 4000 times. The mixture is heated to a constant temperature to phase-convert to a monolayer (S745). Here, the constant temperature may be about 46 ° C. That is, the constant temperature here is a temperature at which the sealed mixture can cause phase conversion into a monolayer. The PNIPMA solution, the chitosan solution or the alginate solution are alternately added to the phase-converted material and added to the fourth volume to coat the lipsomal bubble to provide a first mixture (S746). Here, the fourth volume may be 0.4 ml. Perfluorobutane is added to the first mixture, and the second mixture is provided by mixing with a shaker having a rotation per minute more than the predetermined number of times (S841). The second mixture is filtered using at least one thin film filter (S931). In step S931, the second mixture is first filtered using a first thin film filter having a pore size of 900 μm, and then the second mixture is first filtered using a second thin film filter having a pore size of 6 μm. Can be filtered second. After two filtering, bubbles with a size of 3 ~ 450um can be obtained. Bubbles having a radius of 3 ~ 450um size are classified by size using a centrifuge (S971). Bubbles of a certain size are collected and stored from bubbles classified by size, and perfluorobutane can be added to a container containing bubbles classified by size to ensure bubble stability.

It is noted that the amount of material presented in each step of FIG. 21 is a relative amount, not an absolute amount. That is, the material presented in each step may represent a ratio of relative amounts shown in the description of FIG. 20.

When the bubbles are generated as described with reference to FIGS. 17 to 21, bubbles of a specific size may be generated, and the functional material delivery device of FIG. 1 may be mixed with a functional material and applied to an object. Using (10) to irradiate an ultrasonic wave having a wavelength interlocked with a bubble of a specific size to the mixture containing the functional material and the bubble, the bubble vibrates and generates a volume flow in the surrounding solution, and micro-streaming at the interface. , Jet streaming is generated by asymmetric destruction. Thus, the functional material is well absorbed by the subject.

Since the bubble prepared according to the embodiment of the present invention is considerably larger in size than the contrast agent, when an ultrasonic wave having a wavelength interlocked with the contrast medium is applied to the bubble, the bubble vibrates at a percentage of the existing size under the influence of the ultrasonic wave. do. Therefore, the change of length occurs in proportion to the radius of the bubble, and thus the surface area changes in proportion to the square of the length of the radius. As a result, the fluid around the bubble is affected in proportion to the cube of the length of the radius. That is, the size of the bubble and the flow of the surrounding fluid of the bubble has a relation of the cube. When the bubble is located at the interface between the solid and the fluid, the size and the surroundings of the bubble are also generated in the micro streaming and jet streaming phenomena caused by the movement of the solid boundary without any movement toward the solid interface due to the change of boundary conditions. The volumetric flow of is in a cubed relationship. Therefore, it is preferable to use a relatively large bubble in order to more effectively deliver the large functional material through the epidermis for a short time.

Bubbles prepared according to the bubble manufacturing method for promoting the delivery of the functional material according to an embodiment of the present invention may have a radius of 3 ~ 450um as described above. The functional material delivery device 10 of FIG. It may be easier for the substance to be delivered to the epidermis of the subject.

Although bubbles may be produced as shown in FIGS. 17 to 21, bubbles may be generated using ultrasonic waves. That is, the boiling point of the perfluorinated carbon-based material is below 10 ℃ ~ 35 ℃ ℃ material is stored in the functional material mixture at 5 ℃ or less and applied to the subject. In this case, an unstable environment in which bubbles can be easily generated by the body heat of the body is created. Ultrasonic waves of 1 to 10 MHz are irradiated to the mixed solution applied to the subject for several msec. Accordingly, bubbles of a specific size can be generated by irradiation of ultrasonic energy. When irradiated with ultrasonic waves of a relatively low frequency of 20 ~ 1 MHz in conjunction with the size generated based on the bubble group formed in this way, the functional material can more easily penetrate the epidermis of the subject.

Hereinafter, a method of delivering a functional substance to a subject by taking vitamins as an example.

First, 0.01 g of Ascobic Acid is diluted in 100 ml of distilled water. Bubbles having a radius of 30 μm prepared by one of the manufacturing methods described with reference to FIGS. 17 to 21 are added to the diluent at a volume ratio of 0.1%. That is, 100 μl of a bubble having a size of 30 μm of a pre-prepared radius is added to 100 ml of Ascobic Acid aqueous solution, and then applied to the object (skin). The cavitation phenomenon is generated in the bubble formed by irradiating the object with 200 kHz ultrasonic waves.

Such functional material may be included in distilled or saline solution in some cases in a suitable% ratio, and then ultrasonic waves may be applied after adding a small amount of bubbles at a% ratio. In this case, the buffer solution may be manufactured in a gel type or the like, and a mask pack may also be used.

Embodiments of the present invention can be widely applied in the field of skin beauty and hair loss.

Although the invention has been described above with reference to preferred embodiments, those skilled in the art will be able to variously modify and change the invention without departing from the spirit and scope of the invention as set forth in the claims below. I will understand.

Claims

Providing a first mixture comprising a proportion of shell material;

Mixing the first mixture and the core material to provide a second mixture;

Filtering the second mixture to provide bubbles having a radius of 3 to 450 um; And

Method of producing a bubble to facilitate the delivery of the functional material comprising the step of separating the bubble having a size of the radius of 3 ~ 450um by size.
The method of claim 1, wherein the shell material is albumin.
The method of claim 2, wherein the core material is liquefied perfluorobutane,

Providing the first mixture,

Diluting an amount of albumin in a first volume of saline;

Extracting a second volume of the mixture from the diluted mixture; And

Cooling the second volume of mixture to below a predetermined temperature to provide the first mixture,

Providing the second mixture,

Adding a third volume of liquefied perfluorobutane to the cooled mixture to provide the second mixture;

Providing the bubble,

Filtering the second mixture using at least one thin film filter,

The step of separating the bubbles by size is characterized in that the filtered second mixture is classified by size using a centrifugal separator to facilitate the delivery of the functional material of the foam manufacturing method.
The method of claim 3, wherein providing the second mixture comprises:

Method for producing a bubble to facilitate the delivery of the functional material, characterized in that the mixture is added to the liquefied perfluorobutane is added to a shaker having a predetermined number of revolutions per minute.
The method of claim 3, wherein providing the second mixture comprises:

Method for producing a bubble for promoting the delivery of the functional material, characterized in that carried out by applying an ultrasonic wave to the mixture liquefied perfluorobutane.
The method of claim 1, wherein the shell material is lipid based.
The method of claim 6, wherein the core material is liquefied perfluorobutane,

Providing the first mixture,

Diluting a first volume of glycerol and a second volume of propylene glycol in a third volume of saline;

Adding a first weight of DPPC powder and a second weight of DPPA powder to the diluted mixture;

Dissolving the powder by heating the mixture to which the powder is added at a constant temperature range;

Extracting a fourth volume of the mixture from the additive in which the powder is dissolved; And

Cooling said fourth volume of mixture to below a predetermined temperature to provide said first mixture,

Providing the second mixture,

Adding a fifth volume of liquefied perfluorobutane to the cooled mixture to provide the second mixture;

Providing the bubble,

Filtering the second mixture using at least one thin film filter,

The step of separating the bubbles by size is characterized in that the filtered second mixture is classified by size using a centrifugal separator to facilitate the delivery of the functional material of the foam manufacturing method.
The method of claim 1, wherein the shell material is phospholipid.
The method of claim 8, wherein the core material is liquefied perfluorobutane,

Providing the first mixture,

Dissolving a first weight of DPPC powder in a first volume of chloroform;

Placing the dissolved solution in a container and evaporating in a vacuum chamber;

Adding a saline buffered with a second volume of ginseng salt to the vesicle formed on the surface of the container;

Extracting a third volume of the mixture from the salt added material; And

Cooling the third volume of the mixture to a predetermined temperature or less to provide the first mixture,

Providing the second mixture,

Sealing by adding a fourth volume of liquefied perfluorobutane to the cooled mixture;

Heating the closed mixture to 46 ° C. to phase convert it into a monolayer; And

Mixing the phase-converted material with a shaker having at least a predetermined number of revolutions per minute to provide the second mixture,

Providing the bubble,

Filtering the second mixture using at least one thin film filter,

The step of separating the bubbles by size is characterized in that the filtered second mixture is classified by size using a centrifugal separator to facilitate the delivery of the functional material of the foam manufacturing method.
A main body portion which is mixed with a functional material and outputs an ultrasonic wave having a wavelength that is interlocked with the size of bubbles delivered to the object as a mixture; And

A pro part connected to the main body part and contacting the object to which the mixture is applied to the ultrasonic wave oscillation transmitted from the main body part, and having a pro part,

Ultrasonic oscillation having a wavelength associated with the size of the bubble generates a cavitation phenomenon in the bubble applied to the object.
11. The functional material delivery device according to claim 10, wherein the bubble has a radius of 3 to 450 um.
The apparatus of claim 10, wherein the mixture comprises the functional material, the bubble, and distilled water.
11. The functional substance delivery device according to claim 10, wherein the functional substance is any one of vitamin C, vitamin A, anti-wrinkle agent, whitening agent, depilatory agent and anti-hair loss agent.
The apparatus of claim 10, wherein the main body includes an input unit configured to set the wavelength of the ultrasonic wave such that the wavelength of the ultrasonic wave has a wavelength that is linked to the size of the bubble.