WO2007060741A1

WO2007060741A1 - Method of substance infiltration and apparatus therefor

Info

Publication number: WO2007060741A1
Application number: PCT/JP2005/021778
Authority: WO
Inventors: Kakuji Tojo; Tetsuo Nishiyama
Original assignee: Laseine Co., Ltd.
Priority date: 2005-11-28
Filing date: 2005-11-28
Publication date: 2007-05-31

Abstract

Cosmetic preparations containing vitamin B12 of 1355.38 molecular weight are applied to the epidermis. Cosmetic electrode (3) is brought into contact with the relevant portion, and ultrasonic infusion is carried out for 30 min. Thereafter, further a positive current is passed through the cosmetic electrode (3) to thereby carry out iontophoresis. It has been found that by carrying out the above ultrasonic infusion under the condition of ultrasound intensity (Iu) × ultrasonic irradiation time (Dp) ≤ 20, the amount of active ingredient having infiltrated in the epidermis increases to 217 times that exhibited in the instance of simple coating, to 18 times that exhibited in the instance of ultrasonic infusion alone, and to 12 times that exhibited in the instance of iontophoresis alone. Thus, efficient infiltration of active ingredients in the epidermis can be attained.

Description

Substance permeation method and apparatus

Technical field

[0001] The present invention relates to a substance permeation method and apparatus, and more particularly to a substance permeation method and apparatus for allowing an active ingredient to penetrate the epidermis by ultrasonic introduction or ion introduction. Background art

[0002] In recent years, substance penetration methods that penetrate active ingredients into the epidermis have been widely used not only in the medical field but also in the field of beauty, and in particular, ultrasonic introduction using ultrasound (Sonophoresis) and ion introduction using an electric field. The substance permeation method of the following patent documents 1-5 using (Iontophoresis) is known.

In Patent Document 1, the transdermal transport of molecules is performed by combining ultrasonic introduction with a physical sensor such as ion introduction. After ultrasonic introduction and ion introduction at the same time, ion introduction is performed. By doing so, the amount of penetration of force lusein is increased. (Page 47: Example 5)

In Patent Document 2, the absorption amount of L-ascorbic acid is increased by performing ultrasonic introduction and ion introduction simultaneously. (After paragraph 0039)

Patent Document 3 describes administration of a drug through the epidermis by introduction of ultrasonic waves, and an indication S for applying a physical driving force such as ion introduction after the introduction of ultrasonic waves is made. . (Paragraphs 0045, 0049)

In Patent Document 4, a cleansing mode (ion derivation) is first performed, and then a notching mode (ion introduction) and ultrasonic introduction are performed simultaneously to infiltrate the medicinal component into the epidermis. (Paragraphs 0018, 0019)

Patent Document 5 states that ultrasonic introduction and ion introduction are performed simultaneously to infiltrate the bracentric extract and vitamin C derivative (paragraph 0046), and vitamin C is infiltrated by introducing ultrasound after ion introduction. Become. (0049 paragraph)

Patent Document 1: Japanese Patent Publication No. 10-509632

Patent Document 2: Japanese Patent Laid-Open No. 2001-259045 Patent Document 3: Japanese Translation of Special Publication 2002-500075

Patent Document 4: Japanese Unexamined Patent Application Publication No. 2004-201718

Patent Document 5: Japanese Patent Laid-Open No. 2005-245521

Disclosure of the invention

Problems to be solved by the invention

[0003] However, due to the excellent defense function of the stratum corneum, the active ingredient can hardly penetrate the epidermis. For example, the amount of penetration can be increased by increasing the ultrasonic intensity in the introduction of ultrasonic waves. However, if the ultrasonic intensity is increased too much, there is a risk that the epidermis burns or the skin tissue is destroyed, and even if the substance permeation method described in Patent Documents 1 to 5 is used, the active ingredient cannot be sufficiently permeated. I helped.

In addition, although the active ingredient can be permeated into the epidermis by using the substance permeation methods of Patent Documents 1 to 5, most of the permeated active ingredient penetrates into the dermis layer inside the epidermis, and the dermis. Since the capillaries in the layer flow to the whole body, the effect of the active ingredient on the epidermis was not sufficiently obtained.

Furthermore, in Patent Documents 1 to 5, although the active ingredient can permeate the epidermis, the permeation of the active ingredient cannot be controlled in time, and the active ingredient is permeated only when necessary. I couldn't do it.

In response to such problems, the present invention is a substance penetration method and apparatus capable of rapidly penetrating the active ingredient into the epidermis, and a substance capable of obtaining the effect of the active ingredient on the epidermis over a long period of time. It is an object of the present invention to provide a permeation method and apparatus, and a substance permeation method and apparatus capable of permeating an active ingredient in a necessary amount when necessary.

Means for solving the problem

[0004] The substance permeation method according to claim 1 includes ultrasonic introduction in which an ultrasonic wave is applied to the skin coated with an active ingredient, and an ion for bringing a positive current into contact with the skin coated with the active ingredient. Introducing a substance into the epidermis by introducing the above active ingredient,

First, ultrasonic introduction is performed under the conditions of ultrasonic intensity (Iu) X ultrasonic irradiation time (Dp) ≤ 20, and then ion introduction is performed. [0005] The substance permeation method according to claim 2 includes ultrasonic introduction in which an ultrasonic wave is applied to the skin coated with an active ingredient, and an ion that causes a positive current to flow through the skin coated with the active ingredient. Introducing a substance into the epidermis by introducing the above active ingredient,

After introduction of ultrasonic waves, ion introduction is performed and the active ingredient is permeated into the epidermis. Then, the current to the introduction electrode is reversed to minus to perform ion derivation.

[0006] The substance permeation method according to claim 3 is the substance permeation method according to claim 2, wherein the ion introduction is performed after introducing the ultrasonic wave and allowing the active ingredient to penetrate the epidermis. And ion derivation alternately.

[0007] The substance permeation device according to claim 10 is an addition to the introduction electrode that is brought into contact with the position where the active ingredient is applied, the vibration element that vibrates the introduction electrode to introduce ultrasonic waves, and the introduction electrode. In a material permeation apparatus equipped with a current supply means for introducing ions by flowing a current of

A control means for controlling the vibration element and the current supply means;

The control means vibrates the vibration element under the condition of ultrasonic intensity (Iu) X ultrasonic irradiation time (Dp) ≤ 20, and after introducing the ultrasonic wave by vibrating the vibration element, the current supply means It is characterized in that ion introduction is performed by operating the.

[0008] The substance permeation apparatus according to claim 11 includes an introduction electrode that is brought into contact with a position where an active ingredient is applied, a vibration element that introduces ultrasonic waves by vibrating the introduction electrode, and the introduction electrode. In the substance permeation apparatus equipped with a current supply means for introducing ions by passing a positive current,

In addition to providing a control means for controlling the vibration element and the current supply means, the current supply means switches the direction of the current to the introduction electrode and allows a negative current to flow to allow ions to be derived.

The control means oscillates the vibration element and introduces ultrasonic waves, then causes the current supply means to flow a positive current through the introduction electrode to introduce ions, and further introduces a negative current to the current supply means. It is characterized by flowing ions through the electrode for ion extraction [0009] The substance osmosis device according to claim 12 is the substance osmosis device according to claim 11, wherein the current supply means is a positive current with respect to the introduction electrode under the control of the control means. It is characterized by flowing negative currents alternately.

The invention's effect

[0010] According to the first and tenth aspects of the present invention, ion introduction is performed after ultrasonic introduction, and Iu (ultrasound intensity) and Dp (ultrasound irradiation time) By making the relationship Iu X Dp≤20, the effects of ultrasonic introduction and ion introduction can be obtained synergistically. In the experiment, 217 times the amount of penetration was measured compared to the case where the active ingredient was simply applied.

Further, according to the inventions of claim 2 and claim 11, the active ingredient that has penetrated into the epidermis by performing ultrasonic introduction and ion introduction is further subjected to ion derivation, and then immediately from the epidermis to the dermis. Can be prevented, and the effect of the active ingredient on the epidermis can be maintained for a long time.

Furthermore, according to the invention of claim 3 and claim 12, the active ingredient that has penetrated into the epidermis by ultrasonic introduction and ion introduction thereafter performs ion introduction, ion derivation, and current interruption of ion introduction. The amount of permeation from the epidermis to the dermis can be controlled in time, and the active ingredient can be permeated as necessary when necessary. Best Mode for Carrying Out the Invention

[0011] The illustrated embodiment will be described below. FIGS. 1 and 2 show a beauty device 1 as a substance infiltration device used in the substance infiltration method according to the present invention. It penetrates the epidermis to obtain a beauty effect.

This cosmetic device 1 is provided with a housing 2 made of resin, a cosmetic electrode 3 as a hemispherical introduction electrode provided on the upper front surface of the housing 2, and provided on both sides of the housing 2. A grasping electrode 4 having a substantially elliptical shape is provided, and four LEDs 5 and three switches 6 are provided below the cosmetic electrode 3.

The casing 2 is formed so as to be gripped by the user's hand shown by the imaginary line in FIG. 1, and the conductive gripping electrodes 4 are provided on both side surfaces above the casing 2 for use. Thumbs up And the tip part of the index finger comes into contact.

As the gripping electrode 4, the surface of the resin component having a conductive plating or a metal product can be used.

Next, FIG. 3 shows a view of the beauty device 1 cut along III-III in FIG. 1. The casing 2 can be divided into a front case 2a and a back case 2b. Are fixed to each other by screws 7 above both cases 2a and 2b.

The cosmetic electrode 3 is conductive and has a substantially hemispherical shape, and protrudes from the upper side of the surface side case 2a to the outside. As the cosmetic electrode 3, a conductive plating is applied to the surface of the grease component. Thing and metal things can be used.

A flange 3a protrudes from the bottom surface of the cosmetic electrode 3 in the direction of expanding the diameter. The flange 3a is sandwiched between the surface side case 2a and the ring-shaped attachment member 8 so that the cosmetic electrode 3 is It comes to be fixed to case 2a.

Furthermore, a conventionally known vibration element 9 is fixed to the center of the bottom surface of the cosmetic electrode 3, and the vibration of the vibration element 9 propagates to the cosmetic electrode 3 to generate ultrasonic waves from the cosmetic electrode 3. Come on!

[0013] A conventionally known rechargeable battery 10 is provided on the back side case 2b, and the rechargeable battery 10 is connected to a connection port 11 provided at the lower ends of both cases 2a and 2b by a lead wire (not shown). . By inserting a power plug (not shown) into the connection port 11, the rechargeable battery 10 can be charged!

Further, between the front side case 2a and the back side case 2b, control as current supply means and control means connected to the cosmetic electrode 3, the gripping electrode 4, and the vibration element 9 by a lead wire (not shown). A substrate 12 is provided.

The control board 12 vibrates the vibration element 9 and causes a current to flow through the cosmetic electrode 3 and the gripping electrode 4. When a positive current flows through the cosmetic electrode 3, a negative current flows through the gripping electrode 4. When a negative current is applied to the cosmetic electrode 3, a positive current is applied to the gripping electrode 4.

The control board 12 can be operated by the switch 6 described above. By operating the switch 6, the course registered on the control board 12 or the course registered in the control board 12 can be obtained. It is possible to select the ultrasonic intensity of the ultrasonic introduction and the current value of the ion introduction 'voltage value. The control board 12 automatically vibrates the vibration element 9 and supplies current to the cosmetic electrode 3 according to the selected content. The contents of the selected course and information on the ON / OFF of the power supply are displayed on the above LED5, and if necessary, a warning sound is generated by a not-shown speaker power provided in the housing. This prompts the user to touch the gripping electrode 4 during ion introduction.

In this beauty device 1, by operating the switch 6, the functions of ultrasonic introduction, ion introduction, and ion derivation can be used.

First, as shown in Fig. 4, the skin tissue is laminated in the order of surface force in the order of the epidermis layer, the dermis layer, and the subcutaneous tissue. Of these, the surface of the epidermis layer has a stratum corneum thickness of 10 to 20 m. Layers are formed, and organs such as capillaries and nerves are developed in the dermis layer.

The stratum corneum is formed by stacking 15 to 20 layers of flat corneocytes filled with fibrous protein (keratin). A lamellar structure is formed to fill the space between the corneocytes.

Introducing ultrasonic waves (Sonophoresis), the ultrasonic wave disrupts the tissue structure of the epidermis layer by bringing the cosmetic electrode 3 into contact with the surface of the stratum corneum while the vibrating element 9 is vibrated. It has come to promote the penetration of.

Specifically, when the skin tissue is irradiated with ultrasonic waves, a fine cavity is formed in the epidermis layer, and when microbubbles generated in the cavity are crushed (cavity phenomenon: Cavitation), the stratum corneum is caused by the impact. The structural arrangement of the material is disturbed to create gaps, and the active ingredient penetrates into the gaps.

Iontophoresis is performed by bringing the cosmetic electrode 3 to which a positive current is passed into contact with the surface of the stratum corneum, and bringing the thumb and index finger into contact with the grasping electrode 4 so that the cosmetic electrode 3 and the skin are brought into contact with each other. An electric field due to a potential difference is generated between the tissue and the tissue. As a result of the generation of the electric field, ionic substances can penetrate into the stratum corneum by electro repulsion. Vitamin B12 as an active ingredient here is a force that is a non-ionic substance. Can do.

The reason is that electroosmosis is involved, and when electroosmosis causes the solvent (mainly water) to move toward the surface force epidermis of the stratum corneum, it is thought that the effective component also moves according to the flow. The

In the ion derivation (Reverse-Iontophoresis), the thumb electrode and the index finger are brought into contact with the gripping electrode 4 through which a positive current is passed, and the cosmetic electrode 3 is brought into contact with the surface of the stratum corneum. An electric field due to a potential difference is generated between the skin and the skin tissue.

The electric field at this time has a potential gradient opposite to that of the ion introduction described above, and the surface force of the stratum corneum moved by the ion introduction, whereas the solvent moved from the dermis layer to the surface of the stratum corneum. As a result, it is thought that the active ingredient also moves according to the flow.

Conventionally, this ion derivation has been used mainly in the field of beauty equipment to obtain a cleansing effect for removing foreign substances in the epidermis.

And the beauty equipment 1 of a present Example is used as follows.

First, the user preliminarily applies a lotion or gel containing an active ingredient such as vitamin B12 on the part where the cosmetic effect is desired. At this time, instead of applying the lotion, it is also possible to cover the portion where the cosmetic effect is desired with a fiber soaked in the lotion.

Next, when the user operates the switch 6 of the beauty device 1 and selects a course registered in advance, the control board 12 first vibrates the vibration element 9 to generate ultrasonic waves from the beauty electrode 3, The user touches the cosmetic electrode 3 to the position where the lotion is applied and introduces ultrasonic waves.

When the ultrasonic introduction is performed for a predetermined time, the control board 12 generates a warning sound from the speaker, stops the ultrasonic irradiation, finishes the ultrasonic introduction, and holds the master finger and the index finger with respect to the user. Prompt to touch electrode 4.

When the control board 12 detects that the user's thumb and index finger have touched the gripping electrode 4 or when the warning sound is generated and the force is applied for a predetermined time, the control board 12 applies a positive current for cosmetic purposes. Flow through electrode 3, user makes cosmetic electrode 3 Ion introduction is performed in contact with the position where water is applied.

When the ion introduction is performed for a predetermined time, the control board 12 generates a warning sound again from the speaker, stops the supply of the positive current to the cosmetic electrode 3, and this time the brass current is used for the gripping. Ion derivation over a specified time by flowing to electrode 4

[0016] In the beauty device 1 of the present embodiment, the functions of ultrasonic introduction, ion introduction, and ion derivation are performed under the following conditions.

First, in ultrasonic introduction, the ultrasonic frequency can actually be set in the range of 5k to 20MHz, but the beauty device of this embodiment can select the ultrasonic frequency of lk to 5MHz by the above switch 6 in particular. It becomes like this.

The ultrasonic intensity (lu) can be set in three levels: H (High), M (Middle), and L (Low), where H = 5.20 (W / cm ² ) and M = 6. 19 (W / cm ² ) and L = 7.37 (W / cm ² ). (See Fig. 6) And the time of ultrasonic introduction can be set to 3-30 minutes each.

Here, in the beauty device 1 of this embodiment, the duty cycle (Duty Cycle) that actually vibrates the vibration element 9 is set in accordance with the ultrasonic intensity as well as the viewpoint power of circuit protection, and the ultrasonic intensity (lu) is It is 5.40 (%) for H, 3.60 (%) for M, and 2.10 (%) for L.

In other words, if this duty cycle is taken into consideration, if the ultrasonic introduction time is 30 minutes, the actual ultrasonic irradiation time (Dp) is 1.62 (min) when the ultrasonic intensity (lu) is H, When M is 1.08 (min), when L is 0.54 (min).

Next, with respect to ion introduction, a positive current is applied to the cosmetic electrode 3 in a current density range of 0.1 to 1.0 mA / cm ² and a voltage of 3 to 12 V! /.

As for ion derivation, a positive current is passed through the gripping electrode 4 in a current density range of 0.1 to 1. OmA / cm ² and a voltage of 3 to 12V.

[0017] Regarding the introduction of ultrasonic waves, the ultrasonic intensity (I u) and the ultrasonic irradiation time (Dp) can be freely set within the range of the following formula 1.

IuX Dp≤20 '-' (Equation 1) The graph shown in Fig. 5 shows Iu X Dp on the horizontal axis and the penetration rate of active ingredient ((dQZdt) pZ (dQZ dt) c) on the vertical axis. Using the equipment used in the experiment, an experiment was conducted in which vitamin C penetrates the hairless mouse epidermis at an ultrasonic frequency of 1ΜΗζ and an ultrasonic intensity of 4.3 WZcm ² .

As can be seen from FIG. 5, it has been found that the penetration rate of the active ingredient decreases when it exceeds 1100. The reason for this is thought to be that when Iu X Dp exceeds 20, enzyme deactivation occurs in the skin tissue, and the penetration of the active ingredient is hindered. In other words, in the case of the beauty device of the present embodiment, as shown in FIG. 6, the ultrasonic wave is introduced for a maximum of 71 minutes for ultrasonic intensity (Iu) force ¾, a maximum of 90 minutes for M, and a maximum of 151 minutes for L. It becomes possible.

Under the above conditions, by operating the beauty equipment in the above-described order, the active ingredient of the skin lotion can be more efficiently infiltrated than before, and the effect of the active ingredient can be maintained for a long time. It becomes possible.

[0018] Next, an experiment was conducted on a substance permeation method using the beauty device 1. In addition to the introduction of ultrasonic waves, ion introduction, and ion derivation, experiments were also performed on simple application of lotion.

In the experiment, the epidermis removed from the abdomen of 6-8 week old female hairless mice was used, and Vitamin B12 with a molecular weight of 1355.38 (is this expression correct?) Was used as an active ingredient in skin lotion. This vitamin B12 has water-soluble and nonionic properties.

In order to measure the flux of vitamin B12, an in vitro experiment was performed using the instruments shown in FIGS. 7 (a) to (c).

[0019] Fig. 7 (a) is a device that measures the amount of vitamin B12 permeation by simple application. Receptor cell 21 is divided into two spaces at the center, and hot water is used to surround receptor cell 21. A water jacket 22 to be circulated and a force are also formed, and each space of the receptor cell 21 is filled with a phosphate buffer L as a receptor. This phosphate buffer L is kept at 37 ° C. by the hot water circulating in the water jacket 22.

Then, the epidermis S is set above the receptor cell 21 so that the stratum corneum faces upward, and the surface of the epidermis S is a Hyde mouth gel containing 2% VB12 (hereinafter referred to as drug gel DG). And Hyde Mouth Gel not containing VB12 (hereinafter referred to as “Blank Gel BG”) were applied so as to be located above each space of the receptor cell 21.

After that, vitamin B12 was passively permeated into epidermis S without applying any external force to drug gel DG and blank gel BG. This experiment is called the Control experiment (hereinafter referred to as Co experiment).

[0020] The experiment shown in Fig. 7 (b) is an apparatus for measuring the amount of vitamin B12 permeation by introduction of ultrasonic waves. The experiment is performed using the receptor cell 21 and the like used in the above experiment.

In this experiment, a gel holder made of silicon rubber having a thickness of 1 mm was previously placed on the upper surface of the epidermis (not shown), and holes were formed in two locations in the gel holder in accordance with the position of the receptor cell 21 space. Is drilled.

Next, the blank gel BG is filled in one hole of the gel holder, and in this state, the cosmetic electrode 3 of the cosmetic device 1 is brought into contact, and the ultrasonic frequency is set to 300 kHz and the ultrasonic intensity is set to H (ultrasonic wave) Intensity 5.21 WZcm ² , duty cycle 5.4%) and irradiated with ultrasonic waves for 30 minutes, after which the blank gel BG on the epidermis S was completely removed.

Hereinafter, the operation until the blank gel is removed is referred to as ultrasonic pretreatment.

After this ultrasonic pretreatment, the above-mentioned drug gel DG was applied to 3πιΓ on the side where the blank gel BG was placed during the ultrasonic pretreatment, and the blank gel BG was applied to 3πιΓ on the other side. As in the Control experiment in (a), vitamin B12 was passively permeated into the epidermis S. This experiment is called SP experiment below.

[0021] The experiment shown in Fig. 7 (c) is an instrument for measuring the amount of penetration of vitamin B12 by iontophoresis. The experiment was performed using the receptor cell 21 used in the above experiment, and the ultrasonic pretreatment was performed. An experiment was conducted for each of the epidermis S and the epidermis S that had been subjected to ultrasonic pretreatment.

3ml each of the above drug gel DG and blank gel BG is applied to the epidermis S, electrodes 23 and 24 are brought into contact with each of the drug gel DG and blank gel BG, and the cosmetic electrode 3 of the cosmetic device 1 is connected to the electrode 23. Then, a positive current was applied, and a gripping electrode 4 was connected to the electrode 24 so that a negative current was applied. In the following, an experiment on skin S without ultrasonic pretreatment is called an IP experiment, and an experiment on epidermis S with ultrasonic pretreatment is called an SP + IP experiment.

[0022] Explaining the above experimental results, Fig. 8 shows the measurement results of the flux of vitamin B12 (gZ cm ² Zhour) in each experiment. In this experiment, the power from the beauty device 1 was 1.48 mW. In the SP + IP experiment, the power was set at 1.8 mW.

As a result, the SP experiment flux is 12 times that of the Co experiment, the IP experiment flux is 21 times that of the Co experiment, the SP + IP experiment flux is 217 times that of the Co experiment, and SP + IP The experimental flux was 22 times that of the SP experiment and 11 times that of the IP experiment.

From the above, it is possible to dramatically increase the amount of penetration of the active ingredient by performing ion introduction after ultrasonic pretreatment by ultrasonic introduction, compared to simply applying lotion. Compared to the case where ultrasonic introduction and ion introduction were carried out alone, the penetration amount of the active ingredient could be increased.

In particular, in this experiment, the ultrasonic pretreatment by ultrasonic introduction is performed and then ion introduction is performed, so that the effects of ultrasonic introduction and ion introduction can be simply added together. It has been found that the effects can be obtained synergistically.

[0023] Next, during the SP + IP experiment, an operation for stopping the current in ion introduction (IP stop) and an operation for deriving ions by switching the current flow to the electrodes 23 and 24 are performed. Line V, an experiment was conducted in which the amount of penetration of the active ingredient was changed over time.

Figure 9 shows the experimental results. The vertical axis shows the amount of penetration of active ingredient (g / cm ² ) and the horizontal axis shows the elapsed time. Together with the results of the Co experiment and SP experiment It shows the experimental results combining ultrasonic introduction, ion introduction, ion derivation, and IP termination. Specifically, for the skin that was ultrasonically treated for 30 minutes after ultrasonic introduction, ion introduction, ion derivation, ion introduction, IP stop, ion introduction, ion derivation every hour from the start of the experiment. Switching operation was performed in the order of ion introduction and IP stop.

As a result, the flux of the active ingredient during ion derivation is about 2.48 (μg / cm hour), which is 1Z137 and Co experiment compared to the flux in the SP + IP experiment. The flow rate was 1.6 times higher.

In addition, the flux of the active ingredient at the time of IP stop is about 18.82 (/ ζ ₈ Ζ.πι ² Ζΐ ηιι :). As a result, the permeation amount increased more than the flux at the time of the P experiment.

Based on the above, even if ion penetration (SP + IP) is performed after ultrasonic wave introduction, even if the penetration amount of the active ingredient is increased, the penetration of the active ingredient can be performed immediately if ion derivation is performed at an arbitrary time. It was found that can be deterred.

In addition, by stopping the current in the middle of ion introduction, a penetration amount almost equivalent to that of simple ultrasonic introduction can be obtained. It can be seen that the time can be controlled.

[0024] In the above embodiment, the penetration of the active ingredient of the cosmetic by the beauty device 1 has been described. However, based on the above experimental results, the medicine can be applied through the epidermis as in the following second embodiment. It can be carried out.

In other words, in the case of drugs such as narcotic analgesics, unlike cosmetics, it is necessary to penetrate the drug to the dermis and spread the active ingredient throughout the body by means of capillaries, while the blood concentration of the drug must be kept constant.

The substance permeation apparatus in this example is a substance permeation apparatus having the functions of ultrasonic introduction, ion introduction, and ion derivation, similar to the beauty device 1, and further includes a sensor for measuring the blood concentration of the active ingredient. Prepare.

The substance penetration method for infiltrating the active ingredient of this drug is the same as in the case of infiltrating the active ingredient using the cosmetic device 1 described above. After introducing the ultrasonic wave first, ion introduction is performed, and the active ingredient penetrates the epidermis. Let

By introducing ions after ultrasonic introduction in this way, the active ingredient can rapidly penetrate into the capillaries of the dermis layer, and then the blood concentration of the active ingredient is measured by the sensor. By automatically switching between ion introduction, ion derivation, and current interruption so that the blood concentration remains constant, the active ingredient can penetrate into the blood as needed, making it optimal. Drug administration can be performed.

[0025] In the above examples, vitamin B12 having a molecular weight of 1355.38 has been described as an example of an active ingredient. However, even an active ingredient having a molecular weight of 1000 or less can efficiently penetrate into the epidermis. Even with an active ingredient having a molecular weight of about 10,000, the above effect can be obtained. Brief Description of Drawings

FIG. 1 is a front view relating to a beauty device used in this example.

FIG. 2 is a side view of the beauty device.

FIG. 3 is a cross-sectional view taken along line III in FIG.

圆 4] A diagram explaining the skin structure.

FIG. 5 is a graph showing the relationship between IuX Dp and permeability.

FIG. 6 is a table showing the relationship between the ultrasonic intensity output by the beauty device of this example and the ultrasonic irradiation time.

[Fig. 7] Shows the equipment used in the experiment. (A) shows the Control experiment, (b) shows the SP experiment, and (c) shows the IP experiment.

[Fig. 8] A table showing the experimental results for the flux of each experiment.

FIG. 9 is a table showing experimental results on the amount of penetration and the elapsed time.

Explanation of symbols

[0027] 11 Beauty / Beauty Machine Equipment 3 Beauty Electrode

4 Grip electrode 9 Vibration element

12 Control board 21 Receptor Senore

23 Probe 24, 25 electrodes

S epidermis DG drug gel

BG blank gel

Claims

The scope of the claims

[1] The above-mentioned active ingredient is applied to the epidermis by introducing ultrasonic waves that irradiate the skin to which the active ingredient has been applied, and ion introduction in which a positive current is passed through the skin to which the active ingredient has been applied. In the method of penetrating substances,

A substance infiltration method characterized in that ultrasonic introduction is first performed under the conditions of ultrasonic intensity (Iu) X ultrasonic irradiation time (Dp) ≤ 20, and then ion introduction is performed.

[2] The above-mentioned active ingredient is applied to the epidermis by introducing ultrasonic waves that irradiate the epidermis coated with the active ingredient, and ion introduction in which a positive current is passed through the epidermis coated with the active ingredient. In the method of penetrating substances,

A substance permeation method characterized in that ion introduction is performed after ultrasonic introduction and the active ingredient is permeated into the epidermis, and then the current to the introduction electrode is reversed to minus to perform ion derivation.

[3] The substance permeation method according to [2], wherein the ion introduction and the ion derivation are alternately performed in a state where an ion is introduced after ultrasonic introduction and an active ingredient is infiltrated into the epidermis.

4. The substance permeation method according to claim 3, wherein the supply of current to the introduction electrode is stopped for a predetermined time during the ion introduction.

[5] The ultrasonic frequency in the above ultrasonic introduction is set in the range of 20k to 5M (Hz), the ultrasonic intensity is set in the range of 0.5 to 5.0 (WZcm ² ), and the ultrasonic irradiation time is set in the range of 1 to 30. 5. The substance permeation method according to claim 1, wherein the substance penetration method falls within a range of (min).

[6] The ultrasonic frequency in the above ultrasonic introduction is in the range of 295k to 300k (Hz), the ultrasonic intensity is in the range of 5. 20-7.37 (WZcm ² ), and the ultrasonic irradiation time is 2. 71- 3. The material permeation method according to any one of claims 1 and 5, wherein the range is 84 (min).

[7] The substance permeation method according to any one of claims 1 to 6, wherein the power in the ion introduction is in the range of 1.46 to 8 (mW).

[8] The current in the ion introduction is in the range of 0.3 to L (mA) and the voltage is in the range of 6 to 12 (V). The method of penetrating substances according to claim 7

[9] The substance permeation method according to any one of claims 1 to 8, wherein the molecular weight of the active ingredient is 1000 to L0000.

[10] An introduction electrode that is brought into contact with the position where the active ingredient is applied, a vibration element that vibrates the introduction electrode to introduce ultrasonic waves, and a current that conducts ion introduction by flowing a positive current through the introduction electrode. In a substance permeation apparatus comprising a supply means,

The control means vibrates the vibration element under the condition of ultrasonic intensity (Iu) X ultrasonic irradiation time (Dp) ≤ 20, and after introducing the ultrasonic wave by vibrating the vibration element, the current supply means The substance permeation apparatus characterized by performing ion introduction by operating

[11] An introduction electrode that is brought into contact with the position where the active ingredient is applied, a vibration element that introduces ultrasonic waves by vibrating the introduction electrode, and a positive current is supplied to the introduction electrode to perform ion implantation. In the substance permeation apparatus comprising a current supply means,

The control means oscillates the vibration element and introduces ultrasonic waves, then causes the current supply means to flow a positive current through the introduction electrode to introduce ions, and further introduces a negative current to the current supply means. The substance infiltration device is characterized in that ions are led out through an electrode for use.

12. The substance permeation apparatus according to claim 11, wherein the current supply means causes a positive current and a negative current to flow alternately to the introduction electrode under the control of the control means.

[13] The current supply means, wherein the current supply means stops the supply of the current for a predetermined time while a positive current is flowing to the introduction electrode under the control of the control means. 13. The substance permeation device according to any one of 12 above.

[14] A sensor for measuring the blood concentration of the active ingredient is provided, and the control means supplies a positive current to the introduction electrode according to the blood concentration of the active ingredient, and a negative value to the introduction electrode. Switching between supply of current and stop of supply of current to the introduction electrode Item 13. The substance infiltration device according to Item 13.

When a positive current flows through the introduction electrode, a gripping electrode through which a negative current flows is provided, and when the control means stops the vibration element and operates the current supply means, the gripping electrode 15. The substance vibration device according to claim 11, wherein a warning is issued so as to touch the surface.