JP4768404B2 - Beauty method by iontophoresis - Google Patents

Beauty method by iontophoresis Download PDF

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JP4768404B2
JP4768404B2 JP2005323854A JP2005323854A JP4768404B2 JP 4768404 B2 JP4768404 B2 JP 4768404B2 JP 2005323854 A JP2005323854 A JP 2005323854A JP 2005323854 A JP2005323854 A JP 2005323854A JP 4768404 B2 JP4768404 B2 JP 4768404B2
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skin
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ascorbic acid
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JP2007131547A (en
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亨 岡本
明子 高橋
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株式会社 資生堂
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  The present invention relates to a cosmetic method using iontophoresis and an iontophoresis kit. More specifically, the present invention relates to a cosmetic method by continuous treatment of iontophoresis of tranexamic acid and ascorbic acid, and a kit therefor.

Conventionally, iontophoresis (iontophoresis) technology has been used in the medical field such as dentistry, ophthalmology, urology, etc. to promote percutaneous or mucosal absorption of an active ingredient. Iontophoresis is the application of a relatively low current (for example, about 10 V, about 0.5 mA / cm 2 ) to the skin for several minutes to several hours. A technique that facilitates skin delivery. For example, administration by iontophoresis has been reported for a water-soluble steroid (Patent Document 1), lidocaine salt as a local anesthetic (Patent Document 2), and the like.

  In recent years, iontophoresis of water-soluble drugs, particularly vitamin C or a derivative thereof (ascorbic acid or a derivative thereof) has been performed in the beauty industry in beauty skin clinics and esthetics. Since vitamin C is negatively charged by simply dissolving the powder in water, transdermal delivery can be enhanced by iontophoresis from the negative pole side. Vitamin C has a whitening effect and prevents acne, spots, wrinkles, skin aging, etc. Therefore, vitamin C iontophoresis is expected to bring a higher whitening effect and skin quality improvement effect. Has been. However, the conventional treatment with only vitamin C is not sufficient in the treatment effect, and it has been required to provide a higher whitening and skin quality improvement effect.

Tranexamic acid and its derivatives are generally used as antiplasmin agents, and even in cosmetic applications, they are blended in various external preparations etc. as having whitening action and anti-skin roughening action. There was a problem. Therefore, it was strongly desired to enhance transdermal delivery of tranexamic acid, but tranexamic acid is an amphoteric compound, and apparently almost in the neutral pH range (about 7.3 to 7.8) of aqueous solutions usually used in cosmetics and the like. It has not been dissociated, and since tranexamic acid is simply dissolved in water as is done for vitamin C, almost no current flows, and so far, transdermal delivery of tranexamic acid has been achieved by iontophoresis. There has been no report about increasing it.
International Publication No. 96/011034 Pamphlet Japanese Patent Laid-Open No. 10-316590

  In view of the circumstances as described above, an object of the present invention is to provide an iontophoresis treatment method capable of providing higher whitening and improving skin quality, and a kit therefor.

  Although tranexamic acid is an amphoteric compound having a carboxyl group and an amino group, it was hardly dissociated and could not be ionized by simply dissolving it in water. We found that transdermal delivery of tranexamic acid can be markedly enhanced by weakly acidic pH of 3.5 to 6.5 and positively charging tranexamic acid and introducing ions from the positive electrode side. First successful.

  The present invention relates to iontophoresis (hereinafter referred to as Cathodal IP) from the negative pole side of conventional vitamin C or a derivative thereof (ascorbic acid or a derivative thereof, hereinafter referred to as ascorbic acid), and from the positive pole side of tranexamic acid. In continuous iontophoresis with iontophoresis (hereinafter referred to as "Anodal IP"), the sequence of treatment has a significant effect on the intradermal pharmacokinetics and effect of the drug, and after the application of tranexamic acid, Anodal IP. It is based on the discovery that the application of Cathodal IP of ascorbic acid can result in a significantly higher surgical effect than the reverse order or iontophoresis alone. Not only can the transdermal delivery of tranexamic acid be given by anodal IP of tranexamic acid prior to the cathodal IP of ascorbic acid, but it also significantly increases the intradermal concentration of ascorbic acid than the cathodal IP of ascorbic acid alone. It is possible to produce a synergistic effect by performing continuous treatment in the above-mentioned treatment order. On the other hand, when reverse treatment sequence, ie, ascorbic acid Cathodal IP followed by tranexamic acid Anodal IP, ascorbic acid introduced into the skin was affected by the subsequent force of tranexamic acid Anodal IP. The intracutaneous concentration of ascorbic acid is significantly reduced, and the treatment effect is lower than when performing ascorbic acid Cathodal IP alone.

  As a conventional continuous treatment of iontophoresis, a combination of iontophoresis of vitamin C and iontophoresis of placenta (human placenta extract), which is said to have moisturizing and rejuvenating effects, is known. So far, there has been no report on how the sequence of treatment in continuous treatment affects the intradermal pharmacokinetics and the effect of treatment.

  The cosmetic method of the present invention is characterized in that a tranexamic acid-containing composition having a pH of 3.5 to 6.5 is brought into contact with the skin and subjected to Anodal IP, and then the ascorbic acid-containing composition is brought into contact with the skin to apply Cathodal IP. And

  In the cosmetic method of the present invention, after Anodal IP of tranexamic acid, the electrode may be changed immediately and Cathodal IP of ascorbic acid may be applied from above, but from the viewpoint of iontophoresis effect, after Anodal IP of tranexamic acid, Prior to applying Cathodal IP of ascorbic acid, it is preferred to wash the skin to remove the tranexamic acid-containing composition on the skin.

  The cosmetic method of the present invention is, for example, a whitening method although not limited thereto.

  The iontophoresis kit of the present invention comprises a tranexamic acid-containing composition having a pH of 3.5 to 6.5, and an ascorbic acid-containing composition. The tranexamic acid-containing composition is brought into contact with the skin to give Anodal IP. After application, Cathodal IP is applied by bringing the ascorbic acid-containing composition into contact with the skin.

  The kit of the present invention may further include an iontophoresis device, and is not limited, but can be, for example, a beauty kit for whitening.

  In this specification, “Anodal IP” means that a positive electrode is applied to the skin contacted with the composition (that is, ion introduction is performed using the positive electrode as an introduction electrode). “Cathodal IP” means that ions are introduced by applying a negative electrode to the skin in contact with the composition (that is, using the negative electrode as an introduction electrode).

  Not only can the transdermal delivery of tranexamic acid be given by anodal IP of tranexamic acid prior to the cathodal IP of ascorbic acid, but it can also enhance the transdermal delivery of ascorbic acid significantly more than the cathodal IP of ascorbic acid alone. Can do. Therefore, the present invention can provide a synergistic effect by continuously applying Anodal IP of tranexamic acid and Cathodal IP of ascorbic acid in the above-mentioned treatment sequence, and can effectively prevent white skin and rough skin in a short period of time. It is possible to bring about an effect.

The pH of the tranexamic acid-containing composition used in the present invention is slightly acidic from pH 3.5 to 6.5. If the pH is lower than 3.5, the skin is too irritating when brought into contact with the skin, and if the pH is higher than 6.5, tranexamic acid does not dissociate sufficiently. More preferably, the pH is 4.5 to 5.5, and most preferably about pH 5.
For example, an organic acid such as citric acid, lactic acid and acetic acid, and / or an inorganic acid such as hydrochloric acid, etc. may be blended with any acid alone or in combination of two or more, and the pH of the composition of the present invention is as described above. Can be adjusted to the desired pH. From the viewpoint of pH stability, safety, and iontophoresis effect, it is preferable to use an organic acid such as citric acid, lactic acid, and acetic acid as a pH adjuster, and citric acid is most preferable. The amount of the acid is an amount that can achieve the desired pH, and is not limited depending on the type of acid used and the amount of tranexamic acid used.For example, when citric acid is used with respect to 2.0% by mass of tranexamic acid, it is usually 0.1. To 0.5% by mass, and more preferably 0.3 to 0.5% by mass. When the blending amount of an organic acid such as citric acid exceeds 0.5% by mass, transdermal delivery of tranexamic acid tends to decrease, and when it is less than 0.1% by mass, the pH stability may be poor.

  As used herein, tranexamic acid includes pharmaceutically acceptable salts thereof. Examples of such tranexamic acid salts include, but are not limited to, metal salts such as magnesium salts, calcium salts, and potassium salts, sulfate salts, and hydrochloride salts.

  The content of tranexamic acid is not particularly limited, but is preferably 0.1% by mass to 10.0% by mass, more preferably 0.5% by mass to 5% by mass, and still more preferably 1% by mass with respect to the total amount of the composition. % To 3% by mass. If the blending amount is less than 0.1% by mass, sufficient whitening or anti-skin roughening effect may not be achieved. Even if the blending amount exceeds 10.0% by mass, the effect corresponding to the increase in the blending amount is obtained. It is not preferable because the enhancement is not observed.

  Ascorbic acid as used herein includes pharmaceutically acceptable derivatives and salts thereof. Examples of ascorbic acid derivatives include ethyl ascorbic acid (vitamin C ethyl) such as ascorbic acid phosphoric acid, ascorbic acid 2-glucoside, 3-O-ethylascorbic acid or 2-O-ethylascorbic acid, etc. Examples thereof include, but are not limited to, magnesium salts, calcium salts, potassium salts and the like. Since it is excellent in stability, for example, ascorbic acid phosphates such as sodium ascorbate phosphate and magnesium ascorbate phosphate are preferably used.

  The content of ascorbic acid is not particularly limited, but is preferably 0.1% by mass to 10.0% by mass, more preferably 1% by mass to 9% by mass, and further preferably 3% by mass with respect to the total amount of the composition. % To 8% by mass. If the blending amount is less than 0.1% by mass, sufficient whitening or anti-skin roughening effect may not be achieved, and if it exceeds 10.0% by mass in the composition, the effect corresponding to the increase in blending amount is seen. Not only does it cause irritation to the skin, but it is not preferable.

  The pH of the ascorbic acid-containing composition is not particularly limited as long as the ascorbic acid is dissociated and negatively charged, but is preferably pH 3.5 to 10.5, more preferably pH 4 from the viewpoint of irritation to the skin. 10.

  Although the tranexamic acid-containing composition and the ascorbic acid-containing composition used in the present invention are not limited, for example, an aqueous solution, a gel-like aqueous solution, a water-containing molded gel, a gel-like ointment, a sheet-form preparation carrying a water-containing molded gel Or an O / W emulsion containing an oil such as squalane or ester oil.

  Furthermore, in addition to the above-described components, these compositions can be appropriately blended with other optional components that are usually used in the intended dosage form such as an aqueous solution, a gel or an emulsion, as necessary. . Such components are not particularly limited, and examples thereof include humectants, thickeners, and organic solvents such as alcohol.

  Examples of the humectant include glycerin, diglycerin, 1,3-butylene glycol, propylene glycol, dipropylene glycol, sorbitol, fructose, mannose, erythritol, trehalose, xylitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, and caronic acid. Is mentioned.

  Thickeners include gum arabic, carrageenan, gum karaya, gum tragacanth, carob gum, quince seed (malmello), casein, dextrin, gelatin, sodium pectate, sodium alginate, methylcellulose, ethylcellulose, CMC, hydroxyethylcellulose, hydroxypropylcellulose , PVA, PVM, PVP, sodium polyacrylate, carboxyvinyl polymer, locust bean gum, guar gum, tamarind gum, cellulose dialkyldimethylammonium sulfate, xanthan gum, agar, bentonite, hectorite, AlMg silicate (Begum), laponite, etc. It is done.

  Examples of the organic solvent include alcohols such as ethanol and isopropanol.

  Furthermore, for example, preservatives such as phenoxyethanol and paraben, antioxidants such as butylhydroxytoluene, tocopherol, and phytin, and, if necessary, buffers or pH adjusters other than the above-mentioned acids or basic substances. However, it is preferable not to contain preservatives or antioxidants from the viewpoint of safety.

Although it is possible to blend the salts, Na + in Anodal IP tranexamic acid, cations such as K +, but also Cl in Cathodal IP ascorbic acid - for anions such as the competing ions, e.g. The amount of salt such as NaCl is preferably 0.5% by mass or less, more preferably 0.1% by mass or less.

  In the cosmetic method of the present invention, any method may be adopted as the method for bringing the composition into contact with the skin, as long as tranexamic acid or ascorbic acid in the composition can be delivered transdermally. For example, an aqueous solution, a gel preparation or an O / W emulsion may be applied directly to the skin, or the composition may be impregnated with gauze or the like and applied to the skin. Moreover, you may affix a sheet-like composition directly on skin. Or you may make a chemical | medical agent storage part integrated with the electrode structure of an iontophoresis apparatus contain a composition, and may make it contact with skin through a pad, an ion exchange membrane, etc. The application site is not particularly limited, and may be any skin of the body such as the face, arms, back, legs, and chest.

  Iontophoresis (Anodal IP or Cathodal IP) is performed by applying a positive electrode or a negative electrode to the skin contacted with the composition. As the iontophoresis method, apparatus, voltage application conditions, and the like, any commonly used one can be used.

  For example, a platinum, carbon, silver, silver chloride electrode or the like can be used as the electrode, and the energization method may be any method such as a direct type, a pulse type, or a pulse depolarization type.

The current density is not limited, but is preferably 0.001 to 0.5 mA / cm 2 , more preferably 0.01 to 0.4 mA / cm 2 , and further preferably 0.05 to 0.3 mA / cm 2 . If it is less than 0.001 mA / cm 2 , the transdermal delivery promoting effect may not be sufficiently obtained, and if it exceeds 0.5 mA / cm 2 , skin irritation may be exhibited.

  The treatment time of Anodal IP and Cathodal IP is also not particularly limited, but is usually 0.5 to 60 minutes, more preferably 1 to 30 minutes per treatment. The treatment time for Anodal IP and Cathodal IP may be the same or different.

  In the cosmetic method of the present invention, the tranexam-containing composition may be contacted with the skin and subjected to Anodal IP, and then the electrode may be changed immediately and the ascorbic acid-containing composition may be contacted from above to apply Cathodal IP. From the viewpoint of the iontophoresis effect, it is preferable to wash the skin and remove the tranexamic acid-containing composition on the skin after applying Anodal IP of tranexamic acid and before applying Cathodal IP of ascorbic acid. The method and means for washing the skin are not particularly limited. For example, the composition on the skin may be removed simply by wiping the skin with a cloth or wet tissue, or the skin may be washed with water or a detergent. .

  The interval between the tranexamic acid Anodal IP treatment and the ascorbic acid Cathodal IP treatment is not particularly limited as long as the effects of the present invention can be achieved, but is usually within 15 minutes, more preferably within 10 minutes.

  The cosmetic method of the present invention may be performed alone or in combination with any other cosmetic method. For example, the cosmetic method of the present invention is applied to the skin after chemical peeling treatment in which a chemical substance such as α-hydroxy acid, trichloroacetic acid, salicylic acid or phenol is applied to the skin and the skin surface layer is peeled off at a certain depth. As a result, drying, inflammation, rough skin, etc. due to chemical peeling can be effectively reduced, and a synergistic whitening and skin-beautifying effect can be brought about.

The iontophoresis kit of the present invention may further include an ion introducer in addition to the above tranexamic acid-containing composition and ascorbic acid-containing composition. By setting the iontophoretic agent and the iontophoresis device as a set, the treatment becomes simpler, for example, at home. In the present specification, the “ion introducer” is not particularly limited as long as it can flow a weak current of about 0.001 to 0.5 mA / cm 2 to the skin through the positive electrode and the negative electrode. Any of those used in cis can be used. In addition, since a weak current can be applied to the skin more easily and simply, a sheet-type micro battery embedded in a patch sheet may be used in the present invention. For example, a patch sheet incorporating a 3V battery can be applied to the skin simply by applying it to the skin via a hydrogel that covers the electrode. By changing the position of the applied electrode, Anodal IP and Cathodal IP can be switched and processing can be easily stopped by peeling the sheet.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated concretely, this invention is not limited to the following Example.

1. Examination of treatment sequence in in vitro skin permeation experiment When a weak current is applied by applying an electrode to the skin in iontophoresis, the force due to electro-repulsion of the same charge in the electric field formed by the current And by the force due to electro-osmosis caused by the flow of water from the positive electrode to the negative electrode, which occurs when the cation adsorbed on the negatively charged stratum corneum is attracted to the negative electrode, It is believed to provide transdermal delivery of the components. FIG. 1 schematically illustrates the mechanism of transdermal delivery by iontophoresis.

  Tranexamic acid is weakly acidic (pH 3.5 to 6.5) and is positively charged and ionized by Anodal IP, while ascorbic acid is ionized by Cathodal IP. Therefore, when iontophoresis of tranexamic acid and ascorbic acid is performed continuously, it is expected that the drug that has penetrated into the skin by iontophoresis will receive various forces by applying an opposite electric field immediately after that. It was thought that the intradermal dynamics also changed. Therefore, we first examined in vitro skin permeation experiments how the order of introduction (treatment order) in the continuous treatment of tranexamic acid Anodal IP and ascorbic acid Cathodal IP affects the intradermal dynamics of the drug.

Tranexamic acid (trans-4-Aminomethylcyclohexane-carboxylic acid: hereinafter referred to as TA) (Daiichi Pharmaceutical Co., Ltd.) and sodium ascorbyl-2-phosphate (hereinafter referred to as APS) (Showa Denko) The tranexamic acid-containing composition (TA preparation) and ascorbic acid-containing composition (APS preparation) were prepared using the formulations shown in Table 1. All blending amounts are expressed in mass% with respect to the total amount of the composition:

experimental method
in vitro skin permeation experiment
In vitro transdermal experiments were performed using vertical cells (Franz cells). Wear hairless mouse skin (Hoshino Test Animal Breeding) on Franz cell, add 3 ml of drug formulation to donor side facing stratum corneum, and phosphate buffered saline (PBS) on receiver side facing dermis , PH 7.5) (Takara Bio Inc.) was filled with 7.5 ml. Using a function generator (FG273; manufactured by KENWOOD) as a power source, an Ag / AgCl electrode was incorporated, and an experiment was conducted while confirming with a digital multimeter so that 0.28 mA / cm 2 was obtained. FIG. 2 shows an outline of an in vitro skin permeation experiment. The experimental schedule is also shown in Table 2 below:

When using the positive electrode as the introduction electrode (Anodal IP), use the Ag electrode on the donor liquid side and the AgCl electrode on the receiver liquid side. Conversely, when using the negative electrode as the introduction electrode (Cathodal IP), use the Ag electrode on the donor liquid side. Using an AgCl electrode and an Ag electrode on the receiver liquid side, a current was applied at 0.28 mA / cm 2 for 30 minutes. In TA → APS, TA formulation Anodal IP was performed for 30 minutes, and then the donor solution was removed and washed 3 times with PBS, and then APS formulation Cathodal IP was performed for 30 minutes. In the case of APS → TA, the reverse, that is, Cathodal IP of APS preparation was performed for 30 minutes, then the donor solution was removed, washed 3 times with PBS, and then Anodal IP of TA preparation was performed for 30 minutes. The receiver solution was sampled every 10 minutes up to 30 minutes, and the accumulated permeation amount of each was determined. After the experiment was completed, the skin was collected and separated into two layers, the stratum corneum and the epidermis (corneal stratum corneum) and the dermis by thermal exfoliation, and extracted with ion-exchanged water at 37 ° C for 16 hours. And the concentration of TA in the skin was measured by HPLC with CAPCELL PAK and analyzed with a mass spectrometer (MS).

  FIG. 3 shows the results of cumulative transmission amounts of APS and TA.

  Cumulative APS permeation (APS → TA) after 30 minutes of TA Anodal IP followed by APS Cathodal IP (TA → APS) and after APS Cathodal IP (TA → APS) (Upper) increased with almost the same slope regardless of the order of introduction, and the value 30 minutes after the start of introduction was almost the same. However, when APS → TA was introduced in the order, APS Cathodal IP was canceled. After a lag time of about 10 minutes, it showed a behavior that became convex without becoming flat.

  On the other hand, the cumulative amount of TA transmission (bottom) increases with a similar slope both in the order of APS → TA and in the order of TA → APS, and the value 30 minutes after the start of introduction is almost the same, and TA → APS The behavior of TA when introduced in this order showed a behavior that became flat after a lag time of about 10 minutes after TA's Anodal IP was discontinued.

  Although not shown, normally when ion energization is turned off, drug permeation is observed with the same diffusivity for about 10 minutes after it is turned off, but after that, the permeation stops and a flat inclination is observed. I know I will take it. Therefore, when introduced in the order of TA → APS, the TA introduced earlier is not significantly affected by the power of Cathodal IP of APS thereafter, whereas when introduced in the order of APS → TA, it is introduced first. APS is greatly affected by the subsequent force of TA's Anodal IP, especially the force of electro-osmosis, and the APS in the skin is pushed into the receiver solution, temporarily increasing the accumulated permeation amount, It is thought that the accumulated transmission amount of APS showed a behavior that became convex without becoming flat after a lag time of 10 minutes.

  FIG. 4 shows the results of the intradermal concentration (corneal layer epidermal concentration and dermal concentration).

Corneum epidermis concentration of APS is contrast was TA → the APS 2.5 [mu] g / cm 2, an APS → TA at 0.11 g / cm 2 (showing the dermal concentration similar tendency), intradermal of APS It was found that the concentration was greatly influenced by the order of introduction. Although not shown in the figure, the corneal epidermis concentration after 30 minutes in the passive system in which APS is simply applied and no current is passed is about 0.4 μg / cm 2 , and the APS Cathodal IP is followed by TA Anodal IP. When done, the stratum corneum epidermis concentration (0.11 μg / cm 2 ) of APS was lower than that of the passive system. As mentioned above, because the APS introduced earlier was affected by the force of TA's subsequent Anodal IP, especially the force of electro-osmosis, the APS in the skin was pushed into the receiver solution, It is thought that APS was excreted from the skin, and the intradermal concentration of APS became lower than the passive intradermal concentration. Furthermore, the corneal epidermal concentration of APS Cathodal IP alone is 1.5 μg / cm 2 (not shown), whereas the corneal epidermal concentration of APS from TA → APS is 2.5 μg / cm 2 , By performing TA Anodal IP prior to APS Cathodal IP, the intradermal concentration of APS was significantly increased compared to APS Cathodal IP alone.

On the other hand, the stratum corneum concentration of TA is a TA → APS in 2 [mu] g / cm 2, an APS → TA at 3 [mu] g / cm 2, (shows a dermal concentration similar tendency) the difference remains at about 1.5 times In addition, the intradermal concentration of TA was not significantly affected by the order of introduction.

  From the above results, in the continuous iontophoresis treatment of cathodal IP of ascorbic acid and ananodal IP of tranexamic acid, the treatment sequence has a significant effect on the intradermal kinetics of the drug, especially ascorbic acid. It was suggested that it is important to apply Cathodal IP of ascorbic acid after Anodal IP. Furthermore, by applying the tranexamic acid Anodal IP prior to the ascorbic acid Cathodal IP, the intradermal concentration of ascorbic acid was significantly increased compared to the case of ascorbic acid Cathodal IP alone. It was suggested that synergistic effects could be obtained by continuous treatment with acid Anodal IP and ascorbic acid Cathodal IP.

2. Next, we examined the effects of continuous treatment with tranexamic acid Anodal IP and ascorbic acid Cathodal IP in an in vivo experiment.

Tranexamic acid (trans-4-Aminomethylcyclohexane-carboxylic acid: hereinafter referred to as TA) (Daiichi Pharmaceutical Co., Ltd.) and sodium ascorbyl-2-phosphate (hereinafter referred to as APS) (Showa Denko) The tranexamic acid-containing composition (TA preparation) and the ascorbic acid-containing composition (APS preparation) were prepared using the same formulation as in Table 1 above.

experimental method
In vivo experiment Applying cotton containing each sample to the blackened back skin of Wiser Maple guinea pigs that were treated with 8-Methoxypsoralen and irradiated with UV on the back of hair. Vitalion Iontophoresis was performed from a predetermined electrode side using II (manufactured by Indiva Japan). Table 3 shows the experimental schedule:

In the blank, the sample was not treated at all. In APS (passive), APS was applied and allowed to stand for 3 minutes without flowing current. In APS (IP), APS was applied and Cathodal IP was applied for 3 minutes. In TA → APS, TA Anodal IP was applied for 3 minutes and then APS Cathodal IP was applied for 3 minutes. Conversely, in APS → TA, APS Cathodal IP was applied for 3 minutes and then TA Anodal IP was applied for 3 minutes. In the case of continuous treatment, after the first treatment, the sample was wiped away with a tissue (about 1 minute), and then the next treatment was performed. The treatment is performed once a day for 7 consecutive weeks in each schedule, the skin is measured with a colorimeter (mexameter), and the value obtained by subtracting the measured value after the start of the treatment from the measured value before the start of the treatment is removed (the treatment Effect).

  FIG. 5 shows the skin decolorization effect on the 39th day. After the TA Anodal IP, the continuous treatment of the APS Cathodal IP (TA → APS) is significantly higher than the APS Cathodal IP treatment (APS (IP)), which is usually performed in beauty clinics, etc. Decolorization effect was shown. On the other hand, the decoloring effect by continuous treatment in the reverse order (APS → TA) was lower than the decoloring effect by APS Cathodal IP alone. As described above, it is considered that the APS previously introduced into the skin was discharged deep into the skin under the influence of the subsequent force of TA Anodal IP.

  Based on the above results, in the continuous iontophoresis treatment of tranexamic acid Anodal IP and ascorbic acid Cathodal IP, the treatment sequence had a significant effect on the treatment effect, and ascorbic acid was administered after tranexamic acid Anodal IP was applied. It was suggested that synergistic effects were brought about by the application of Cathodal IP, and that it was possible to have a significantly higher treatment effect, especially a whitening effect, than the conventional treatment of Ascorbic acid with Cathodal IP alone.

  Hereinafter, formulation examples of the tranexamic acid-containing composition and the ascorbic acid-containing composition used in the cosmetic method or iontophoresis kit of the present invention are shown. In addition, all compounding quantities are represented by the mass% with respect to the composition whole quantity. In the present invention, a tranexamic acid-containing composition and an ascorbic acid-containing composition having the following formulation can be used in any combination.


Tranexamic acid-containing composition (Formulation Example 1)
Compounding ingredients Compounding amount (% by mass)
Ion exchange water 97.6
Tranexamic acid 2.0
Citric acid (food) 0.4
pH 4.9

Tranexamic acid-containing composition (Formulation Example 2)
Compounding ingredients Compounding amount (% by mass)
Ion exchange water 87.1
Tranexamic acid 2.0
Citric acid (food) 0.4
Alkylene oxide derivative 10.0
Phenoxyethanol 0.5
pH 5.1

Tranexamic acid-containing composition (Formulation Example 3)
Compounding ingredients Compounding amount (% by mass)
Ion exchange water 87.1
Tranexamic acid 2.0
Citric acid (food) 0.4
Glycerin 10.0
Phenoxyethanol 0.5
pH 5.0

Tranexamic acid-containing composition (Formulation Example 4)
Compounding ingredients Compounding amount (% by mass)
Ion exchange water 87.1
Tranexamic acid 2.0
Citric acid (food) 0.4
1,3-butylene glycol 10.0
Phenoxyethanol 0.5
pH 5.1

Tranexamic acid-containing composition (Formulation Example 5)
Compounding ingredients Compounding amount (% by mass)
Ion exchange water 87.1
Tranexamic acid 2.0
Citric acid (food) 0.4
Ethanol 10.0
Phenoxyethanol 0.5
pH 5.2

Ascorbic acid-containing composition (Formulation Example 1)
Compounding ingredients Compounding amount (% by mass)
Ion exchange water 86.7
Ascorbic acid 2.0
KOH (reagent) 0.8
Alkylene oxide derivative 10.0
Phenoxyethanol 0.5
pH 6.1

Ascorbic acid-containing composition (Formulation Example 2)
Compounding ingredients Compounding amount (% by mass)
Ion exchange water 81.0
Sodium ascorbate phosphate 8.0
Citric acid 0.5
Glycerin 10.0
Phenoxyethanol 0.5
pH 8.0

Ascorbic acid-containing composition (Formulation Example 3)
Compounding ingredients Compounding amount (% by mass)
Ion exchange water 87.1
Ascorbic acid glucoside 2.0
KOH (reagent) 0.4
1,3-butylene glycol 10.0
Phenoxyethanol 0.5
pH 6.5

Ascorbic acid-containing composition (Formulation Example 4)
Compounding ingredients Compounding amount (% by mass)
Ion exchange water 87.47
3-O-ethylascorbic acid 2.0
Na citrate 0.03
Ethanol 10.0
Phenoxyethanol 0.5
pH 4.5

  After applying Anodal IP of the tranexamic acid-containing composition of the above-mentioned formulation example, by applying Cathodal IP of the ascorbic acid-containing composition, high whitening and roughening prevention or improvement effects can be brought about.

Schematic diagram of the mechanism of transdermal delivery by iontophoresis Schematic diagram of in vitro transdermal delivery experiment Graph showing the effect of treatment sequence on the cumulative permeation of ascorbic acid and tranexamic acid Graph showing the effect of treatment sequence on intradermal concentrations of ascorbic acid and tranexamic acid The graph which shows the treatment effect by the continuous treatment of tranexamic acid Anodal IP and ascorbic acid Cathodal IP in the in vivo experiment.

Claims (6)

  1. After the iontophoresis (Anodal IP) from the positive electrode side was applied to the skin with a tranexamic acid-containing composition having a pH of 3.5 to 6.5, the ascorbic acid-containing composition was brought into contact with the skin and the negative electrode side. A cosmetic method characterized by applying iontophoresis (Cathodal IP).
  2. The cosmetic method according to claim 1, wherein the skin is washed after the Anodal IP and before the Cathodal IP.
  3. 3. The cosmetic method according to claim 1, wherein the cosmetic method is a whitening method.
  4. A kit for iontophoresis, comprising a tranexamic acid-containing composition having a pH of 3.5 to 6.5 and an ascorbic acid-containing composition, after the tranexamic acid-containing composition is brought into contact with the skin and subjected to Anodal IP The kit is characterized in that Cathodal IP is applied by bringing the ascorbic acid-containing composition into contact with the skin.
  5. The kit according to claim 4, further comprising an ion introducer.
  6. The kit according to claim 4 or 5, which is a whitening beauty kit.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015098295A1 (en) 2013-12-25 2015-07-02 株式会社 Mtg Cosmetic method
WO2019057251A1 (en) 2017-09-22 2019-03-28 Wellstar Gmbh & Co. Kg Cosmetic method for the iontophoretic treatment of human skin

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102137664B (en) * 2008-09-05 2014-08-06 第一三共健康事业株式会社 Pharmaceutical solid preparation having active ingredients separated by boundary therein
JP2014080374A (en) * 2012-10-12 2014-05-08 Yoshihiro Tokutome Composition for iontophoresis

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015098295A1 (en) 2013-12-25 2015-07-02 株式会社 Mtg Cosmetic method
KR20160103049A (en) 2013-12-25 2016-08-31 가부시키가이샤 엠티지 Cosmetic method
US20180193238A1 (en) * 2013-12-25 2018-07-12 Mtg Co., Ltd. Beauty care method
WO2019057251A1 (en) 2017-09-22 2019-03-28 Wellstar Gmbh & Co. Kg Cosmetic method for the iontophoretic treatment of human skin

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