KR100354291B1 - Ascorbic acid composition for epidermal dosaging - Google Patents

Abstract

The present invention relates to an ascorbic acid composition for transdermal administration, wherein the ascorbic acid phosphate salt is injected into the skin by periodically applying a positive voltage of 3 to 20v, a negative voltage of 3 to 20v, and a current of 0.1 to 1.0 mA to the skin. It relates to an ascorbic acid composition comprising. The use of the ascorbic acid composition for transdermal administration of the present invention can be seen to remove blemishes, blemishes, freckles, wrinkles, acne, sebum, skin aging, and whitening.

Description

Ascorbic acid composition for transdermal administration {ASCORBIC ACID COMPOSITION FOR EPIDERMAL DOSAGING}

The present invention relates to an ascorbic acid composition for transdermal administration, and more particularly, to an ascorbic acid composition for transdermal administration that effectively penetrates into the skin an ascorbic acid that is unstable in an aqueous state and has low transdermal administration efficiency.

Ascorbic acid, commonly known as vitamin C, has the effect of keeping skin healthy and attractive. Medically, ascorbic acid is known to promote collagen formation in human skin to slow or prevent the formation of wrinkles and aging of the skin, as well as to inhibit the oxidation of fat and to prevent skin damage caused by solar ultraviolet rays. Ascorbic acid is also known to have the effect of inhibiting the production of histamine, which is thought to be the cause of melanin formation and various allergies, especially those with sensitive skin, that induce pigmentation of the skin. Therefore, attempts have been made to use ascorbic acid as an active substance in cosmetics and pharmaceuticals that have a whitening effect such as elimination of blemishes and freckles and an anti-wrinkle effect.

Ascorbic acid is administered to the human body as a method of oral administration and transdermal administration method. Since oral administration of ascorbic acid uses ascorbic acid in the form of powder, ascorbic acid can be stored and used in a relatively stable form, but the process of delivery to the skin is inefficient, effectively penetrating the skin relative to the total dose. There is a problem that the actual efficiency which is the ratio of the active substance is very low.

In order to increase the efficiency, transdermal administration method that directly administers ascorbic acid to the skin is preferred, but ascorbic acid itself has low transdermal administration efficiency, and ascorbic acid has very low solubility in nonaqueous medium. It is not practical, and dissolution of ascorbic acid in an aqueous medium has high solubility, but it is not practical because ascorbic acid is easily oxidized and loses its inherent function. In order to improve the instability of ascorbic acid, U.S. Patent No. 4,983,382 proposed a method of using water and an organic solvent such as ethanol as a medium, and U.S. Patent No. 5,981,578 is a non-aqueous solution containing ascorbic acid. He also proposed a method of simultaneously applying other products to the skin, such as lotion or lotion containing a solution and water. As another method for improving the instability of ascorbic acid, a method of stabilizing ascorbic acid by forming a derivative by combining another compound with ascorbic acid is known. For example, Korean Patent Application No. 97-23005 discloses a method for synthesizing ascorbic acid derivatives having excellent stability and safety by reacting L-ascorbic acid with 3-aminopropane phosphoric acid, and using the ascorbic acid derivative as an active ingredient. Cosmetic formulations such as lotions, nourishing creams, massage creams, essences, etc. are disclosed, but even when transdermal administration of ascorbic acid is mixed with cosmetics, the skin delivery process is inefficient, resulting in low practical efficiency.

Accordingly, it is an object of the present invention to provide a composition of ascorbic acid for transdermal administration.

Still another object of the present invention is to provide an ascorbic acid composition for transdermal administration in which ascorbic acid penetrates the skin in a stable state.

1 illustrates an electrophoretic device of the present invention.

Figure 2 shows the appearance of the patient before and after the procedure of the present invention,

Figure 3 shows the appearance of bleeding patients after the ascorbic acid composition of the present invention,

Figure 4 shows the appearance of the patient before the procedure of the present invention,

Figure 5 shows the appearance of bleeding patients after the ultrasonic cleaning and ascorbic acid composition of the present invention,

Figure 6 shows the appearance of the acne patient before the procedure of the present invention,

Figure 7 shows the appearance of acne patients after the procedure of ascorbic acid composition of the present invention,

Figure 8 shows the appearance of the acne patient before the procedure of the present invention,

Figure 9 shows the appearance of acne patients after the ultrasonic cleaning and ascorbic acid composition of the present invention,

Figure 10 shows the appearance of the wrinkles before the procedure of the present invention,

Figure 11 shows the appearance of the wrinkles after the ultrasonic cleaning and ascorbic acid composition of the present invention.

In order to achieve the above object, the present invention (a) (i) 20-99% by weight of ascorbic acid metal phosphate salt; And (ii) 1-80% by weight of an additive; 1-10% by weight of a mixture comprising; And (b) 90-99% by weight of water to provide an ascorbic acid composition for transdermal administration.

Hereinafter, the present invention will be described in detail.

The present inventors convert the ascorbic acid into the form of ascorbic acid phosphate salt and transdermally administer it by electrophoresis, the ascorbic acid phosphate is rapidly and efficiently introduced into the skin, and the ascorbic acid phosphate metal salt is injected into the skin. The present invention was completed by discovering that the enzyme is decomposed by an enzyme in a living body to be transformed into ascorbic acid to exhibit specific effects such as melanin production inhibitory effect, and the oxidation of ascorbic acid is prevented or inhibited even in aqueous solution. Ascorbic acid phosphate metal salts used in the invention can be prepared by reacting ascorbic acid, phosphorus oxychloride, and metal chloride salts or can be purchased from Sigma, USA, or Wako or Niko, Japan.

As the preferred metal salt of the ascorbic acid phosphate metal salt of the present invention, sodium salt, magnesium salt, calcium salt, potassium salt and the like can be used, and magnesium salt is most preferred.

Ascorbic acid phosphate metal salt production method of the present invention is as follows.

Acetone and strentth oleum were mixed with L-ascorbic acid at 0 ° C., stirred for 6 hours, and then cooled to −15 ° C. to vacuum dry the obtained crystallized solid. Water and pyridine are mixed with the vacuum-dried reactant, and POCl ₃ is slowly added at 0 ° C. and stirred for 30 minutes while maintaining the pH at 13. Hydrogen chloride (MgCl ₂ 6H ₂ O) was added thereto, stirred for 1 hour to 2 hours, and then the resulting crystals were removed. After addition of methanol, the resulting crystals were stirred to remove the formed crystals. . To this was added MgO with water, stirring and maintaining a pH of 8.5-9. The mixed solution is dropped in methanol, and the resulting crystals are filtered and washed with methanol to obtain magnesium ascorbic acid phosphate.

Ascorbic acid phosphate salts prepared in this way, preferably ascorbic acid magnesium phosphate (magnesium-L-ascorbyl-2-phosphate) is penetrated into the body when the phosphate salt and magnesium pass through the cell membrane ascorbic acid (vitamin Converted to C) has an effective effect on the skin.

Ascorbic acid phosphate prepared by the above method is mixed with α-G-Rutin (Rutin), allantoin, aloe veragel (aloeveragel), trehaose (trehaose) to prepare an ascorbic acid composition for transdermal administration . The composition of the present invention is preferably used by mixing 90-99% by weight of water to 1-10% by weight of the mixture of 20-99% by weight of ascorbic acid metal phosphate salt and 1-80% by weight of the additive. In addition, the additive is preferably composed of 1-25% by weight of α-G-routine, 1-50% by weight of trehalose, 1-50% by weight of aloe vera gel, and 1-50% by weight of allantoin. . The ascorbic acid metal phosphate salt is stable in the aqueous composition, and does not decompose, and forms a very stable composition without discoloration or precipitation with the surfactant.

The ascorbic acid composition for transdermal administration of the present invention is administered to the skin by electrophoresis. Electrophoresis involves iontophoresis, which allows current to pass through an electrolyte containing an ionic substance, and electrophoresis to deliver an uncharged substance into the body by applying a voltage to the skin. Include.

An example of the electrophoresis method is to construct a circuit by contacting the skin coated with an aqueous solution composition containing ascorbic acid phosphate salt to one electrode of the cathode and the anode, and the ascorbic acid phosphate salt is administered to the skin by voltage difference. It is a method of transdermal administration of the active substance using. Apparatus for performing such electrophoresis method is commonly known in the art, for example, US Patent No. 5,314,502, Republic of Korea Patent 154112, 192161, 203225 and the like and its structure is disclosed.

The preferred method of transdermal administration of the present invention generates 3 to 20 volts of positive voltage at 60 mA pulses and 3 to 20 volts of negative voltage at 500 kHz pulses to the percutaneously under a current of 0.1 to 1.0 mA. It is desirable to. If the voltage is greater than 20v, hypersensitivity may be caused by chlorine or a drug in the skin epidermal layer. If the voltage is less than 3v, ascorbic phosphate metal salt may not be formed with electrical energy sufficient to penetrate the cell membrane of the epidermal layer. The charged ascorbic acid penetrates into the skin through the cell pores formed by the electrical shock and then the phosphate is cut off by the phosphatease enzyme located in the intracellular membrane, leaving only ascorbic acid. Ascorbic acid produced in this way can reduce the melanin production by reducing dopaquinone, a major intermediate of tyrosinase reaction in melanocytes, and remove blemishes. Can prevent and eliminate the formation of

In addition, the electrophoresis method of the present invention can not only increase the transdermal permeability of ascorbic acid phosphate salt, but also provide an additional effect of promoting the dissolution and discharging of skin wastes by supplying a current to the skin. Therefore, it is effective in maintaining healthy skin by removing acne and sebum that are continuously secreted to the skin surface causing skin troubles such as contamination of the skin and disorder of excretion of sebaceous glands opening.

In addition, by ultrasonic cleaning the skin prior to the transdermal administration of metal ascorbic acid phosphate salt by electrophoresis according to the present invention can further improve the transdermal administration effect of ascorbic acid. Ultrasonic cleaning according to the present invention is characterized by a cleansing that generates 20-40 Hz ultrasonic vibrations of weak amplitude, a scaling of 20-40 Hz ultrasonic vibrations of strong amplitude, 10-40 Hz, 20-40 Hz with a period of 0.1 mA. The ultrasonic wave is made through three steps of lifting (lifting), and the lifting may be performed after electrophoresis.

When ultrasonic cleaning is performed by the above method, the ultrasonic energy penetrates not only the skin tissue but also the deep part of the body, thereby promoting the activation of cells including the skin, nerves, lymphatic liver, blood stem, muscle layer, and promoting metabolism, and thus the effect of ascorbic acid. To increase.

Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are provided only to more easily understand the present invention, and the present invention is not limited to the following examples.

Example 1

Preparation of Ascorbic Acid Magnesium Phosphate

120 g of L-ascorbic acid was added with 480 ml of acetone and 43 g of stent oleum at 0 ° C., stirred for 6 hours, cooled to −15 ° C., and the crystals formed were vacuum dried. 1.2 liters of water and 300 ml of pyridine were mixed with the vacuum-dried reaction, and 146 g of POCl ₃ was slowly added at 0 ° C. and stirred for 30 minutes at PH13. 70 g of hydrated magnesium chloride (MgCl ₂ 6H ₂ O) was added thereto, and the mixture was stirred and filtered for 2 hours. To the filtrate was added 1 liter of methanol, stirred for 1 hour, filtered and the solution of the filtrate was evaporated and 39 g of MgO was added with water to keep the pH at 8.5-9 with stirring. The mixed solution was slowly dropped into 1.2 L of methanol, and the resulting crystals were filtered and washed with 300 ml of methanol to obtain magnesium ascorbic acid phosphate salt.

Preparation of Transdermal Dosing Composition

0.2 g of ascorbic acid phosphate salt prepared by the above method, 0.02 g of α-G-Routin, 0.1 g of allantoin, 0.1 g of aloe vera gel, 0.1 g of trehaose ), And 5 g of water were mixed to prepare an ascorbic acid composition for transdermal administration.

Electrophoresis Procedure

Figure 1 shows the electrophoretic device of the present invention, characterized in that the power supply unit 1, six piezoelectric elements 2, stainless steel plate (3; SUS), and bar ((4); bar) Include. One pole of current flowing from the power supply unit to the stainless steel plate is transferred to the contacted skin and reaches another pole flowing in the hand-held bar to form a circuit. At this time, the pole of the power supply and the bar can be used as a positive voltage / negative voltage or negative voltage / positive voltage.

In addition, the electrophoretic apparatus of FIG. 1 can transfer ultrasonic vibration to the percutaneous body by using a piezoelectric element, and thus is also used for ultrasonic cleaning.

The method of transdermal administration of the ascorbic acid composition by electrophoresis is as follows.

3-10 ml of the ascorbic acid composition described above is applied to the face, and a positive voltage of 3 to 20v is generated at 60 Hz pulses and a negative voltage of 3 to 20v is generated at 500 Hz pulses to be transdermal under a current of 0.1 to 1.0 mA. Was applied. The method was carried out twice a week.

Example 2

Ultrasonic Cleaning Method

Ultrasonic cleaning was performed with the electrophoresis apparatus of FIG. 1 and was performed in the following steps.

(1) Cleansing: After water was added to the transderm, a weak amplitude 28 Hz vibration was applied to the transderm for 5 minutes.

(2) Scaling: A strong amplitude 28 Hz vibration was applied to the transdermally for 10 minutes.

(3) Lifting: 28 kPa was applied percutaneously for 10 min at 10 mA and 0.1 mA cycles.

Experimental Example

Ascorbic acid was transdermally administered twice a week to patients with severe blemishes, acne skin patients and those with wrinkles by the method of Example 1 and Example 2 to observe the effect according to 1 month, 2 months and the results are shown in Table 1 Shown in The degree of effect was performed by visual inspection and was given 0 points in the worst case and 10 points in the best case.

No ascorbic acid treatment After Ascorbic Acid Treatment No ultrasound Ultrasound Procedure Time (day) 1 month 1 month 2 months 1 month 2 months Remove spots 0 5 7 7 10 Acne removal 0 5 8 6 10 Wrinkle removal 0 4 5 5 7

2, 3, 4, 5, 6, 7, 8, 9, 10 and 11 shows the results of Table 1 in a photograph. Figure 2 shows the appearance before the ascorbic acid composition of the blemish patient, Figure 3 shows the appearance after two months of ascorbic acid composition of the blemish patient. Figure 4 shows the appearance before the ascorbic acid composition of the blemish patient, Figure 5 shows the appearance after two months of ultrasonic cleaning and ascorbic acid composition of the blemish patient. Figure 6 shows the appearance before the ascorbic acid composition of the acne patient, Figure 7 shows the appearance after two months of ascorbic acid composition of the acne patient. Figure 8 shows the appearance before the ascorbic acid composition of the acne patient, Figure 9 shows the appearance after two months of ultrasonic cleaning and ascorbic acid composition of the acne patient. Figure 10 shows the appearance before the treatment of the ascorbic acid composition of the wrinkled area, Figure 11 shows the appearance after two months of ultrasonic cleaning and ascorbic acid composition of the wrinkled site. The ascorbic acid composition had an excellent effect on removing blemishes, removing acne, and removing wrinkles, and further improved when ultrasonic cleaning was performed together.

As described above, the ascorbic acid composition for transdermal administration of the present invention exhibits blemish removal, blemish removal, freckle removal, wrinkle removal, acne removal, sebum removal, skin aging prevention, and whitening effects. In addition, electrophoresis may be performed in combination with the ultrasonic cleaning prior to transdermal administration of ascorbic acid, thereby achieving a synergistic effect on skin beauty.

Claims (12)

delete delete delete delete delete delete delete delete (Correction) (i) 20-99% by weight of ascorbic acid metal phosphate salt; And (ii) 1-80 wt% of at least one additive selected from the group consisting of α-G-routine, trehalose, aloe vera gel and allantoin; 1-10 wt% of a mixture comprising; And (b) 90-99% by weight of water; Composition for transdermal administration through electrophoresis comprising a. (delete) (Correction) The composition according to claim 9, wherein the composition comprises 1-25% by weight of α-G-routine, 1-50% by weight of trehalose, 1-50% by weight of aloe vera gel, and 1-50% by weight. A composition comprising allantoin of. (Correction) The composition according to claim 9, wherein the ascorbic acid phosphate metal salt is magnesium ascorbic acid phosphate.