JP2013075165A - Method for quickly dissolving microneedles - Google Patents

Abstract

The present invention provides a microneedle patch that is rapidly absorbed into the body and a method for using the same.
[Solution]
The rapid dissolution method of the microneedle array of the present invention is characterized in that water is supplied from the back surface of the microneedle array having a substrate having a thickness of 500 μm or less, mainly composed of a water-swellable polymer, and the microneedle array is swollen. To do. At this time, it is preferable to supply moisture using a planar moisture supply source having a moisture transpiration rate of 25 to 70 g / hm ² . The microneedle array can be attached to and held on the skin with a small piece of adhesive tape at several locations around the back surface. As a result, the dissolution time of the microneedles that required about 1 to 3 hours in the conventional method can be shortened to 5 to 20 minutes, and the use of the microneedles becomes easier.
[Selection] Figure 2

Description

  The present invention relates to a method for rapidly dissolving a microneedle for providing a modifying effect and / or a functional effect to the skin surface layer and / or the skin stratum corneum after being inserted into the skin.

  As a method for administering a drug into a human body, there are an oral administration method and a transdermal administration method. Injection is a typical transdermal method of administration. However, injection is an unacceptable technique for many people who must be bothered by a doctor, is painful, and can also be infected with AIDS or hepatitis B. On the other hand, a transdermal administration method using a microneedle array without causing pain has recently attracted attention (Patent Document 1, Non-Patent Document 1).

The skin stratum corneum acts as a barrier for drug permeation, and simply applying a drug to the skin surface does not sufficiently penetrate the drug. On the other hand, by perforating the stratum corneum using a fine needle, that is, a microneedle, the drug permeation efficiency can be remarkably improved as compared with the coating method. A microneedle array is a large number of microneedles integrated on a substrate. A product that is easy to use by adding an adhesive tape for attaching the microneedle array to the skin or a cover sheet for maintaining sterility until use is called a microneedle patch.
Here, the tape means a film or cloth or paper coated with an adhesive.

If a microneedle is made of a material that dissolves in the body and disappears by metabolism, such as carbohydrates, even if the needle breaks and remains in the skin, no accident will occur. In addition, if the drug is contained in the sugar, the inserted microneedle is dissolved in the body, so that the drug can be easily administered intracutaneously or subcutaneously (Patent Document 2). ).
In particular, when a microneedle made of a biosoluble polymer substance such as hyaluronic acid or collagen is inserted into the skin, moisture in the skin diffuses into the microneedle, and the needle portion inserted into the skin swells and then dissolves. As a result, hyaluronic acid and collagen diffuse into the skin and develop an anti-wrinkle action, or drugs and valuable substances that have been dissolved in advance in the needle portion diffuse into the skin (Patent Documents 3 and 4).

  In order for the microneedles to swell and dissolve in the skin, it is necessary to stably hold the microneedle array on the skin surface. Usually, an adhesive protective tape having a larger area than the microneedle array is placed on the microneedle array and pressed against the surface of the skin, and is closely held by the adhesiveness of the protective tape.

  However, this adhesive protective tape greatly affects the solubility of microneedles in the skin. When a protective adhesive tape having a high water vapor permeability is used, moisture entering the microneedle array from the skin evaporates, the microneedles do not swell sufficiently, and the rate at which the drug is diffused into the skin decreases. In addition, when an adhesive protective tape having low water vapor permeability is used, there is a disadvantage that the skin irritation becomes strong because the tape suppresses water evaporation from the skin.

  In any case, if the hydration for swelling the microneedles is only from the skin, it takes a lot of time to swell and dissolve the microneedles. Conventionally, it was necessary to hold the microneedle array on the skin surface for 1 to 3 hours. For this reason, when the microneedle array is worn on the face, it is often worn before going to bed, and it is difficult to wear it at a beauty salon or beauty salon.

  Cosmetics using microneedles were first commercially produced by Cosmedy Pharmaceutical and were launched in October 2008 (Non-patent Document 1). Since the microneedles required a considerable amount of time for swelling and dissolution, there was a strong demand from users to improve the microneedle dissolution rate so that it can be applied quickly.

Special Table 2002-517300 JP 2003-238347 A JP 2009-238772 A JP 2010-029634 A

Gon Ei, Fumio Kamiyama “The Path to Microneedle Product”, Pharmacology, The Pharmaceutical Society of Japan, September 2009, Vol. 69, No. 4, p. 272-276

  The problem to be solved by the present invention is to solve the above-mentioned problems of the prior art by providing a microneedle array that can swell quickly, dissolve quickly, and absorb quickly. It takes time to swell and dissolve the microneedle array because the water supply to the microneedle array was insufficient. We examined the design of a microneedle patch that can easily supply the necessary moisture.

A method for rapidly dissolving a microneedle array according to the present invention (excluding medical practice) made in order to solve the above-described problem is a microneedle array having a substrate having a thickness of 500 μm or less mainly composed of a water-swellable polymer. Water is supplied from the back surface, and the microneedle array is swollen by the water.
Here, the back surface of the microneedle array refers to the substrate surface opposite to the substrate surface on which the microneedles are provided.

  When an appropriate amount of water is supplied from the back surface of the water-swellable microneedle array, the entire surface from the substrate of the microneedle array to the needle swells quickly, and the dissolution rate of the needle in the skin increases. Therefore, the microneedle array, which has conventionally required 1 to 3 hours for dissolution, dissolves in 5 to 20 minutes. At this time, if the amount of water supplied to the microneedle array is too large, the substrate is dissolved before the microneedles are inserted into the skin and swell, and the purpose of dissolving the microneedles in the skin cannot be achieved. If the amount of water supply is too small, the swelling speed becomes slow and the purpose of rapid dissolution cannot be achieved.

As a water supply source from the back surface of the microneedle array, it is appropriate to supply water with a planar water supply source in close contact with the back surface of the microneedle array. At this time, various methods were examined as a method for measuring the amount of water supply, and it was found that the amount of water transpiration (TEWL) of the planar water supply source is highly correlated with the microneedle array swelling speed. The sensor of the TEWL measuring device was brought into close contact with the surface of the surface moisture supply source, the amount of moisture transpiration from the surface was measured, and the correlation with the solubility in the skin of the microneedle was examined using the value as a parameter.
Here, the amount of moisture transpiration (g / hm ² ) refers to the amount (g) by which moisture evaporates from a certain surface per unit time (h) · unit area (m ² ).

  In the present invention, the microneedle array, that is, the microneedle and the substrate are required to be composed of a water-swellable polymer. The following substances can be used as examples of the water-swelling physical polymer. Polysaccharides such as hyaluronic acid, sodium hyaluronate, dextran, chondroitin sulfate, carboxymethylcellulose, proteoglycan, hydroxypropyl cellulose. Proteins such as collagen and gelatin. Water-soluble synthetic polymers such as polyvinyl pyrrolidone. Blending oligohyaluronic acid having a molecular weight of 10,000 or less, hydrolyzed collagen, microhyaluronic acid or the like with the water-swellable polymer is advantageous because the swelling speed is further increased.

The thickness of the substrate of the microneedle array is preferably in the range of 500 μm to 10 μm. If it is thicker than 500 μm, the substrate and needle cannot swell / dissolve in a short time even when water is supplied from the back surface. Therefore, the thickness of the substrate is preferably 500 μm or less. If it is less than 10 μm, the mechanical strength of the microneedle array is weak and it is inconvenient to handle.
The length from the substrate of the microneedle to the needle tip is suitably from 100 μm to 800 μm. The typical area of the microneedle array substrate is 0.5 to 500 cm ² .

The shape of the microneedle array can be various shapes such as a circular shape, an elliptical shape, a quadrilateral shape, a rectangular shape, a crescent shape, a jade shape, a triangular shape, a star shape, and a face mask shape. Here, the shape of the ball is assumed to include a symmetrical shape as shown in FIG. 5 in addition to a normal ball shape.
Moreover, the shape of the adhesive tape used together can also be various shapes such as a circle, an ellipse, a rectangle, a crescent, a ball, a triangle, and a star.
The microneedle and the adhesive tape used together can take various shapes depending on the place of attachment and the purpose of application. The present invention is not limited to these shapes.

When supplying water from the back side to swell and dissolve the microneedle array, use an adhesive tape with high water vapor permeability for the microneedles attached to the skin or a part of the back side of the microneedle array substrate. It is preferable to adopt a method of sticking only to the skin using an adhesive tape.
In the case of using a tape that does not have a very high water vapor permeability, it is desirable that the adhesive tape affixed portion be as small as possible in order to achieve the purpose of rapid dissolution. The adhesive tape application part may be one place, or two or more places.
Note that it is not an essential requirement that the microneedle array is attached to the skin with an adhesive tape. This is because if the wearer lies on his back, inserts microneedles from the upper surface of the facial skin, and covers the surface moisture supply material from above, the microneedle array can be held by the weight.

The water-swellable polymer constituting the microneedle swells when it absorbs moisture, and dissolves into the inside when it swells in the skin. In the conventional method in which an adhesive sheet having a low water vapor permeability is applied to the entire back surface of the microneedle array, moisture is only supplied to the needle from within the skin, so the needle gradually swells and dissolves. Took time.
In addition, there is some irritation at the part where the microneedle is inserted into the skin. This stimulation is contrary to the conventional system for a long time, but the water supply system from the back side according to the present invention dissolves the microneedles quickly, and therefore the skin irritation disappears in a short time.

  When using an adhesive tape, a thing with high water vapor permeability is preferable. Since a thing with high water vapor permeability has good air permeability, you may select a thing with good air permeability. If the air permeability is not good, it is difficult to supply water to the microneedle array, and the microneedle array in that portion is difficult to swell. There is no moisture supply at the part where the non-breathable adhesive tape is applied, and it takes time to dissolve the microneedles in the skin, so that irritation to the skin lasts for a long time.

  An example of a tape having a high water vapor permeability and good air permeability is a non-woven fabric, thin polyurethane (10 μm or less) and paper tape coated with a gas permeable adhesive. Examples of tapes with low air permeability are polyethylene, polyethylene terephthalate, nylon and polypropylene tapes. Or it is good also as an adhesive sheet with high water vapor permeability by pattern-coating normal adhesive on a sheet with high water vapor permeability.

  When the adhesive tape is partially used, the microneedle array part to be attached may not be provided with microneedles. Even if an adhesive tape with good air permeability is used, the part to which the adhesive tape is attached has less water supply than the part to which the adhesive tape is not attached, and it takes time for the microneedles in that part to swell and dissolve. This is because of this. This is because it is desirable that all the microneedles simultaneously swell and dissolve.

  The optimum amount of moisture supplied from the back of the microneedle array was measured using various planar moisture supply sources. Here, the planar material containing moisture is referred to as a planar moisture supply material. When an adhesive tape having a high water vapor permeability is used for the entire back surface of the microneedle, the planar moisture supply material and the adhesive tape are combined to form a planar moisture supply source. When such an adhesive tape is not used, the planar moisture supply material is a planar moisture supply source. When using a surface moisture supply material and a highly water vapor permeable adhesive tape, the sensor of the TEWL measurement device is in close contact with the surface of the adhesive tape (opposite to the surface where the surface moisture supply material is attached), and the amount of moisture transpiration from the surface is measured. did.

In the case of a hyaluronic acid microneedle array having a weight average molecular weight of 100,000, an appropriate water supply amount is preferably 25 to 70 g / hm ² in terms of water transpiration (TEWL), and 35 to 65 g / hm ^{2 is} still more preferable. preferable. If it is less than 25 g / hm ² , the water supply is insufficient and the purpose of dissolution for a short time cannot be achieved. If it is higher than 70 g / hm ^{2, the} objective cannot be achieved because the array substrate dissolves soon before the microneedle array swells.

The optimal water supply can depend on the material of the microneedle array. However, as a result of measuring hyaluronic acid, proteoglycan, chondroitin sulfate, hydroxypropylcellulose, and dextran having a weight average molecular weight of 800,000, no significant difference was found in the optimum water content. Therefore, it was concluded that the measurement results of hyaluronic acid microneedles having a weight average molecular weight of 100,000 also apply to these materials.
In the present invention, since the allowable range of the moisture transpiration amount range is set large, it is considered that the optimum water supply amount is within the same range even if the swelling and dissolution rate due to water is somewhat different. Moreover, all the polysaccharides used for the measurement are extremely hydrophilic and may be considered to be similar in chemical structure. It seems that the optimal amount of water transpiration is different when using hydrophilic materials with much different water solubility.

  As the moisture supplied from the back surface of the microneedle array by the planar moisture supply material, lotion can be suitably used. Specific examples of the planar water supply material include gauze, non-woven fabric, tape or aqueous gel pack containing lotion or cosmetic liquid. The object can be achieved by bringing these into close contact with the back surface of the microneedle.

  It is desirable that the gauze, nonwoven fabric, or aqueous gel pack containing lotion or cosmetic liquid to be attached to the back surface of the microneedle array should be large enough to cover the entire back pores of the microneedle array or larger in each direction. The shape of the gauze, non-woven fabric, tape or gel pack can be any shape depending on the application location, such as a circle, ellipse, rectangle, crescent, bead, triangle, star or face mask.

The microneedle may be impregnated with a cosmetic raw material or a medicinal component, particularly a polymer medicinal component. Examples of cosmetic raw materials include whitening ingredients such as ascorbic acid, vitamin C ethyl, vitamin C glycoside, ascorbyl palmitate, kojic acid, lucinol, tranexamic acid, oily licorice extract, vitamin A derivative, and placenta extract; retinol Anti-wrinkle components such as retinoic acid, retinol acetate, retinol palmitate, EGF, cell culture extract, acetylglucosamine; blood circulation promoting components such as tocopherol acetate, capsine, vanillyl amide, etc .; Diet components such as raspberry ketone, evening primrose extract, seaweed extract Antibacterial components such as isopropylmethylphenol, photosensitizer and zinc oxide; vitamins such as vitamin D2, vitamin D3 and vitamin K; sugars such as glucose, trehalose and maltose;
Examples of the high molecular medicinal component include bioactive peptides and derivatives thereof, nucleic acids, oligonucleotides, various antigen proteins, bacteria, virus fragments, and the like.

  When an appropriate amount of water is supplied from the back surface of the water-swellable microneedle array, the entire surface of the microneedle array from the substrate to the needle swells quickly, and the dissolution rate of the needle in the skin increases. Therefore, the microneedle array, which has conventionally required 1 to 3 hours for dissolution, will be dissolved in 5 to 20 minutes. As a result, the microneedles can be used on a daily basis. In particular, the use of the microneedles in a beauty salon or a beauty salon room becomes practical, and the usability of the microneedle array is improved.

By adhering a planar moisture supply material having a moisture transpiration rate of 25 to 70 g / hm ² to the back surface of the microneedle array, the microneedle array can be quickly swollen and the microneedles can be rapidly dissolved. The optimum conditions for using the microneedle array were clarified, and guidelines for using the microneedle array were given.

Microneedle patch structure. (A) is a top view, (b) is A-A 'sectional drawing. The schematic sectional drawing of the structure which covers a part of back surface of a microneedle array with an adhesive tape, and supplies a water | moisture content from the back surface by a planar water supply material. The schematic sectional drawing of the structure which covers the whole back surface of a microneedle array with a high water vapor-permeable adhesive tape, and supplies a water | moisture content from the back surface by a planar water supply material. The top view of the example of the mounting | wearing method which uses one piece of circular adhesive tape pieces for an elliptical microneedle array. The top view of the example of the mounting | wearing method which uses one piece of rectangular-shaped adhesive tape pieces for a jade-shaped microneedle array. The top view of the example of the mounting method which uses two pieces of circular adhesive tape pieces for an elliptical microneedle array. The top view of the example of the mounting method which uses two rectangular adhesive tapes for a rectangular microneedle array. The top view of the example of the mounting method which uses two pieces of circular adhesive tape pieces for an elliptical microneedle array, and does not provide a microneedle in the part to which an adhesive tape is affixed. The top view of the example of the mounting | wearing method adhere | attached on an ellipse-shaped and ball-shaped microneedle array with a thin adhesive tape. The top view of the example of the mounting method which uses four circular adhesive tapes for an elliptical microneedle array. The top view of the example which covered the whole back surface of the bent elliptical microneedle array with the high water vapor-permeable adhesive tape. The top view of the example which uses four pieces of circular adhesive tape for the back four places of the face-shaped microneedle array. The microneedle array has cut out portions corresponding to the eyes, nose and mouth.

Next, examples of the present invention will be described in detail with reference to the drawings. However, the present invention is not limited to the examples. Moreover, the microneedle array of the present invention was manufactured by a conventional method (Patent Documents 3 and 4).
The hyaluronic acid used in Examples 1 to 9 is manufactured by Kibun Food Chemifa (currently Kikkoman Biochemifa) and has a molecular weight of 100,000 (trade name: FCH-SU, derived from culture). Dextran is purchased by Nippon Bulk Chemical Co., Ltd. (trade name: Dextran 70), and polyvinylpyrrolidone is manufactured by BASF Japan (trade name: Kollidon 12PF). In the present invention, the molecular weight is a weight average molecular weight, which is a value measured by gel permeation chromatography (GPC). The TEWL value measurement was performed using MPA5 & 9 (Integral Co., Ltd.).

The microneedle array (11) of this example has an elliptical shape as shown in FIG. The manufacturing method of this microneedle array is the same as that of Example 1 of Patent Document 3. 0.08 g of sodium hyaluronate (FCH-SU) was dissolved in 1 g of water at room temperature to obtain a hyaluronic acid mixed aqueous solution. From this, a microneedle array was obtained in the same manner as in Example 1 of Patent Document 3. The microneedles are Conide type, with a base diameter of 0.4 mm, a tip diameter of 0.02 mm, and a height of 0.2 mm, arranged in a grid at intervals of 0.6 mm, forming 250 per cm ^2. Has been.
1A is a plan view, and FIG. 1B is a cross-sectional view taken along the line AA ′. The size of the long side is about 30 mm and the short side is about 20 mm. The substrate thickness of this microneedle array is 50 μm. On the back of the microneedle array, a polyethylene adhesive tape (12) 5 mm larger in each direction than the size of the array was applied and integrated. As shown in FIG. 1, the central portion of the tape is cut off leaving 2 mm for each periphery. However, the number of needles written in the figure is not large in order to simplify the figure, but in actuality, 250 needles are formed per 1 cm ² as described above.

After this microneedle array + polyethylene adhesive tape (12) was applied to the skin of the face of the volunteer's face, the essence-containing sheet-like mask (Elixir Superior Retino Vital Eye Mask, manufactured by Shiseido Co., Ltd.) (13) ) Is shown in FIG. However, the illustration of the skin is omitted in the figure.
When it was removed after 20 minutes, it was confirmed that the microneedle was completely dissolved and did not remain at all.

In addition, instead of using a essence-containing sheet-like mask, a sheet obtained by cutting out a sheet of rough cloth or paper into an oval shape or a pendulum shape is used soaking lotion (SK-II facial treatment essence, P & G Japan). Also favorable results were obtained.
In addition to the elliptical shape as in the present example, the cosmetic liquid-containing sheet may have a circular shape, a square shape, a rectangular shape, a triangular shape, a ball shape shape, a star shape, or the like.

Of the microneedle array, the microneedle may not be provided in a portion where the tape is applied. In the case of the present embodiment, the portion around the microneedle array (11) to which the adhesive tape (12) is attached, that is, the inner adhesive tape (12) of the microneedle array (11) in FIG. If the microneedles are not provided in the lower part, skin irritation by the microneedles can be alleviated.
It is difficult for moisture to be supplied to the portion of the microneedle array where the inner adhesive tape is affixed. For this reason, the lower part of the adhesive tape is slow to reach moisture and swell and dissolve slowly. Therefore, if there is a microneedle at that portion, dissolution will be delayed, and the skin will be stimulated for a longer period of time, and the wearer will continue to feel uncomfortable. Therefore, if the microneedles are not provided in the portion covered with the adhesive tape, the skin irritation is reduced, and the wearer can wear the microneedles more comfortably.

  Microneedle arrays were produced in the same manner as in Example 1 except that the thickness of the substrate was changed to 5, 10, 50, 100, 500, and 1000 μm. The microneedle array was circular with a diameter of 2 cm, placed on the skin of the volunteer forearm, and a cosmetic liquid-containing sheet-like mask (Ericseal Superier Retino Vital Eye Mask, manufactured by Shiseido Co., Ltd.) was pressed onto it. In this example, no adhesive tape was used.

Comparative Example 1

  A microneedle array was prepared in the same manner as in Example 1. The thickness of the substrate was 50 μm. The microneedle array was circular with a diameter of 2 cm, and a polyethylene terephthalate (PET) adhesive tape (manufactured by Kosmedy Pharmaceutical Co., Ltd.) that was 5 mm larger in each direction than the array was attached to the entire back surface. A microneedle array with an adhesive tape was affixed to the volunteer's forearm and pressed strongly with a palm from above.

Comparative Example 2

  A microneedle array was prepared in the same manner as in Example 1. The thickness of the substrate was 50 μm. The microneedle array was circular with a diameter of 2 cm, and an adhesive tape (product number 1533L, manufactured by 3M Co., Ltd.) that was 5 mm larger in each direction than the array was attached to the entire back surface. A microneedle array with a tape was affixed to the volunteer forearm and pressed firmly with a palm from above.

In Example 2, Comparative Example 1, and Comparative Example 2, the following evaluation was performed after pasting.
(1) The microneedle patch was removed every 15 minutes after application until 60 minutes, and the time for complete dissolution of the needle was observed.
(2) Immediately after application, the microneedle array applied with a finger was pressed every 30 seconds from the top, and the time until discomfort such as irritation to the skin of the microneedle disappeared was observed.
In the microneedle array in which the uncomfortable feeling lasts for 5 minutes or more, the subsequent observation time was set every 10 minutes.
The results are shown in Table 1. From this table, it can be seen that the complete dissolution time increases as the substrate becomes thicker. Since it is preferable to dissolve completely within 30 minutes, it can be concluded from this result that the thickness of the microneedle array substrate is 10 to 500 μm.

The microneedle array (11) of this example has an elliptical shape as shown in FIG. 0.05 g of sodium hyaluronate (Kibun Food Chemical Co., Ltd., current name Kikkoman Biochemifa Co., Ltd., FCH-80LE) and 0.02 g of dextran were dissolved in 1 g of water at room temperature. A microneedle array was obtained. The microneedles have a conical shape with a root diameter of 0.16 mm, a tip diameter of 0.02 mm, a height of 0.8 m, and are arranged in a grid at intervals of 0.6 mm, forming 250 per cm ^2. Has been. The thickness of the substrate was 50 μm.
The microneedle array was crimped to the volunteer forearm skin. At that time, one peripheral portion of the microneedle array was fixed with one piece of a circular piece of adhesive tape, and water was supplied in the same manner as in Example 1 from above. In this example, the adhesive tape is also attached to a portion where the microneedles are present, but skin irritation is reduced if the microneedles attached to the adhesive tape are not provided.
In this example, 3M (product number 1533L) was used as the adhesive tape. This tape is obtained by applying an acrylic adhesive to paper.

FIG. 5 shows an example in which one piece of rectangular adhesive tape is used for a jade-shaped microneedle array.
In this example, the adhesive tape is also attached to a portion where the microneedles are present, but skin irritation is reduced if the microneedles attached to the adhesive tape are not provided.
In this example, 3M (product number 1533L) was used as the adhesive tape. This tape is obtained by applying an acrylic adhesive to paper.

When the microneedle array is fixed to the skin, two places around the microneedle array can be fixed with a small piece of adhesive tape, and moisture can be supplied from above. FIG. 6 shows an example in which two circular adhesive tapes are used for an elliptical microneedle array. In this example, the adhesive tape is also attached to a portion where the microneedles are present, but skin irritation is reduced if the microneedles attached to the adhesive tape are not provided.
In this example, Nichiban Surgical manufactured by Nichiban was used as the tape. This tape is obtained by applying an acrylic adhesive to paper.

When the microneedle array is pressure-bonded to the skin, two places around the microneedle array can be fixed with a small piece of adhesive tape, and moisture can be supplied from above. FIG. 7 shows an example in which two rectangular adhesive tapes are used in a rectangular microneedle array.
In this example, Nitto Medical, product number ST-245 Solid-4 was used as the tape. This tape is obtained by applying an acrylic adhesive to a nonwoven fabric.

  When the microneedle array is pressure-bonded to the skin, two places around the microneedle array can be fixed with a small piece of adhesive tape, and moisture can be supplied from above. FIG. 8 shows an example in which two circular adhesive tapes are used for an elliptical microneedle array. In this example, since the microneedles are not provided in the adhesive tape attached portion, it has been clarified that the skin irritation is smaller than in the case where it is provided.

  When the microneedle array is pressure-bonded to the skin, a long thin adhesive tape can be used to vertically cut and fix the microneedle, and water can be supplied from the top. FIG. 9 shows an example in which a long thin adhesive tape is used for an elliptical microneedle array and a slanted microneedle array.

  When the microneedle array is pressure-bonded to the skin, four portions around the microneedle array can be fixed with a small piece of adhesive tape, and moisture can be supplied from above. FIG. 10 shows an example in which four circular adhesive tapes are used in an elliptical microneedle array.

  An appropriate amount of water supply was determined for the hyaluronic acid microneedle array. The hyaluronic acid used has a weight average molecular weight of 100,000 (Kikkoman Biochemifa Co., Ltd., trade name FCH-SU) and is a culture-derived hyaluronic acid. Here, the weight average molecular weight is a value measured by gel permeation chromatography.

The microneedle array used in this example has a circular shape with a diameter of 1 cm. Sodium hyaluronate (FCH-SU) (0.08 g) was dissolved in 1 g of water, and this hyaluronic acid aqueous solution was used to produce a template produced in the same manner as in Example 1 of Reference 3 at room temperature. The microneedle is a cone type, and has a root diameter of 0.4 mm, a tip diameter of 0.02 mm, and a height of 0.2 mm. The microneedles are arranged in a grid pattern at intervals of 0.6 mm, and about 250 microneedles are formed per 1 cm ² . The thickness of the substrate was 50 μm.

After the microneedle array was affixed to the lower arm skin of a volunteer, water was supplied from the back surface of the microneedle array by pressing various planar water supply sources on the back surface. The planar water supply source and the microneedle array were peeled from the skin 2 minutes and 20 minutes after application, and the microneedle array was observed with a microscope.
The results are shown in Table 2.

Among the results in Table 2, Example B and Example C use a highly water vapor permeable adhesive tape between the planar water supply material and the back surface of the microneedle array. When the pressure-sensitive adhesive tape was used, the TEWL value was measured from the surface of the pressure-sensitive adhesive tape with the pressure-sensitive adhesive tape applied to the surface of the surface moisture supply material.
Here, FIG. 2 is a schematic cross-sectional view of a configuration in which a part of the back surface of the microneedle array is covered with an adhesive sheet and moisture is supplied from the back surface by a planar water supply material. FIG. 3 is a schematic cross-sectional view of a configuration in which moisture is supplied from the back surface by a planar moisture supply material by covering with a permeable adhesive tape.

In particular, Example B and Comparative Example B have the same planar water supply material and differ only in the presence or absence of an adhesive tape. It can be understood that the TEWL value of the planar water supply source is reduced by interposing the adhesive tape. In Example C, lotion was directly sprinkled in the form of an adhesive tape, and it can be seen that such a case can be achieved through the adhesive tape.
In Example D, the essence-containing sheet-like mask of Example A was used by allowing it to stand at room temperature for 1 hour and drying it slightly. In this way, the TEWL value of the planar moisture supply material can be adjusted.
It can be concluded from the results in Table 2 that the appropriate water supply amount is preferably 25 to 70 g / hm ² in terms of water transpiration (TEWL), and more preferably 35 to 65 g / hm ² .

Proteoglycan (Natural Proteoglycan, Biomatic Japan Co., Ltd.), Hydroxypropylcellulose (Nippon Soda Co., Ltd., HPC-L), Chondroitin sulfate (Maruha Nichiro Foods Co., Ltd.) Surface water supply source for chondroitin sulfate sodium) and dextran (Dextran 40, manufactured by Meisei Sangyo Co., Ltd.), oligohyaluronic acid (Harooligo, Cupy Co., Ltd.), microhyaluronic acid (FCH, Kikkoman Biofemifa Co., Ltd.) The dissolution state of the microneedle was examined by changing Moreover, it tested also when the low molecular valuables were mixed. Trehalose (Hayashibara Co., Ltd.) and acetylglucosamine (Nihon Suisan Co., Ltd.) were used.
0.15 g of these materials were dissolved in 1 g of water to obtain a polymer solution, and microneedles were produced in the same manner as in Example 10. The shape of the microneedle and the thickness of the substrate are the same as those in the tenth embodiment. However, in Examples K and L, the needle height was 0.3 mm. In other examples and comparative examples, the height of the needle was set to 0.2 mm as in Example 10.
The same test as in Example 10 was performed. The results are shown in Table 3. As can be seen from Table 3, for the water-swellable polymers used in this table, the appropriate amount of water transpiration is approximately the same.

  FIG. 11 shows a plan view of an example in which the entire back surface of the bent elliptical microneedle array is covered with a high water vapor permeable adhesive tape. What is necessary is just to cover the surface water supply material from the top after piercing the skin.

  FIG. 12 shows a plan view of an example in which four pieces of circular adhesive tape are used at the four backs of the face-shaped microneedle array. The microneedle array of the present example is designed to be worn on the entire face, and the portions corresponding to the eyes, nose and mouth are cut out.

  The microneedle rapid dissolution method according to the present invention is expected to be widely used in the fields of makeup and beauty.

11 …… Microneedle array 12 …… Adhesive tape or high water vapor permeable adhesive tape 13 …… Cosmetic liquid-containing sheet

Claims (20)

  A method of rapidly dissolving a microneedle array, characterized in that water is supplied from the back surface of a microneedle array having a water-swellable polymer as a main material and a substrate having a thickness of 500 μm or less, and the microneedle array is swollen by the water. (Excluding medical practice). The method for rapidly dissolving a microneedle array according to claim 1, wherein water is supplied using a planar water supply source having a moisture transpiration rate of 25 to 70 g / hm ² (excluding medical practice). Rapid dissolution process of a microneedle array according to claim 1, water loss is characterized by supplying the water by using a surface water source which is 35~65g / hm ² (except for medical practice).   The water-swellable polymer is at least one substance selected from the group consisting of hyaluronic acid, sodium hyaluronate, dextran, chondroitin sulfate, carboxymethylcellulose, proteoglycan, collagen, and gelatin. Rapid dissolution method for microneedle arrays (excluding medical practice).   The method for rapidly dissolving a microneedle array according to claim 1, wherein the water-swellable polymer is a blend of the water-swellable polymer described above with a water-soluble material having a molecular weight of 10,000 or less. Excluding medical practice).   6. The rapid dissolution method for microneedle arrays according to claim 5, wherein the water-soluble material blended with the water-swellable polymer has a weight percentage of 5-40% (excluding medical practice).   The method for rapidly dissolving a microneedle array according to claim 5, wherein the water-soluble material is at least one substance selected from the group consisting of oligohyaluronic acid, microhyaluronic acid, and hydrolyzed collagen. except).   The entire back surface of the microneedle array is covered with a high water vapor permeable adhesive tape, a planar water supply material is placed thereon, and the microneedle array is swollen by the water passing through the high water vapor permeable adhesive tape. Item 2. A method for rapidly dissolving a microneedle array according to Item 1 (excluding medical practice).   2. The method for rapidly dissolving a microneedle array according to claim 1, wherein only a part of the back surface of the microneedle array is covered with an adhesive tape, and the back surface of the microneedle is covered with the planar water supply material to supply moisture. (Excluding medical practice).   The method for rapidly dissolving a microneedle array according to claim 9, wherein small pieces of adhesive tape are used at several locations around the back surface of the microneedle array (excluding medical practice).   The method for rapidly dissolving a microneedle array according to claim 9, wherein a small piece of adhesive tape is used at one location on the back periphery of the microneedle array (excluding medical practice).   The method for rapidly dissolving a microneedle array according to any one of claims 9 to 11, wherein no microneedles are provided on the opposite side of the back surface of the microneedle array to which the adhesive tape is attached. Excluding medical practice).   The method for rapidly dissolving a microneedle array according to claim 8 or 9, wherein the surface moisture supply material includes a lotion or a cosmetic liquid-containing gauze, a nonwoven fabric, or a tape or an aqueous gel pack. Excluding medical practice).   2. The method for rapidly dissolving a microneedle array according to claim 1, wherein the microneedle array contains a cosmetic raw material or a medicinal component (excluding medical practice). A high water vapor permeable adhesive tape covering the back of the microneedle array;
A sheet water supply material provided on the opposite side of the microneedle array of the high water vapor permeable adhesive tape,
A microneedle array characterized in that the microneedle array is swollen by moisture supplied from a planar moisture supply material and passing through a high water vapor permeable adhesive tape. The microneedle array according to claim 12, water loss of planar water supply source is characterized by a 25~70g / hm ^2. Adhesive tape that covers only a part of the back of the microneedle array;
With a planar water supply material provided in close contact with the back of the microneedle,
A microneedle array, wherein the microneedle array is swollen by water supplied from a planar water supply material. The microneedle array according to claim 14, water loss of the planar water supply material characterized in that it is a 25~70g / hm ^2.   The microneedle array according to claim 18, wherein the planar moisture supply material is any one of gauze, non-woven fabric, tape, or aqueous gel pack.   The microneedle array according to claim 15 or 17, comprising a cosmetic raw material or a medicinal ingredient.

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