KR20200090500A - Micro-needle patch and method of mamufacture for palmar hyperhidrosis - Google Patents

Abstract

A microneedle patch according to the disclosed present invention comprises: a plurality of needle parts for penetrating a chemical solution containing an active component into the skin; and a base part for simultaneously supporting the plurality of needle parts to adhere the same to the skin, wherein the active component contains botulinum toxin. According to the configuration, a quantitative amount of botulinum toxin can be infiltrated into an affected area requiring treatment for hyperhidrosis, thereby having excellent treatment stability and accessibility compared to existing injection methods.

Description

Micro needle patch for the treatment of hyperhidrosis and its manufacturing method{MICRO-NEEDLE PATCH AND METHOD OF MAMUFACTURE FOR PALMAR HYPERHIDROSIS}

The present invention relates to a microneedle patch and a method for manufacturing the same, and more particularly, to a microneedle for the treatment of hyperhidrosis that is easy to inject a fixed amount of a drug for the treatment of hyperhidrosis in an area having an area such as a palm, and a manufacturing method thereof .

Hyperhidrosis is an abnormal sweating disorder in response to heat or emotional stimulation, which is more than necessary to regulate body temperature. As a method of treating such hyperhidrosis, a treatment method that temporarily blocks nerve signals such as taking a drug or applying an ointment has been applied. These drugs or ointments have side effects such as suppressing sweat in other parts of the skin and severe hyperstimulation and hyperhidrosis when used for a long time.

Or, to treat hyperhidrosis, sympathectomy was applied to remove the nerves of the affected area through surgery. Since this sympathectomy is a surgical operation that permanently blocks nerve signals, it is difficult to predict an anatomical change in nerve function and a decrease in sweating after surgery or disappearance of each patient.

On the other hand, in recent years, botox is injected into the skin to treat hyperhidrosis, which suppresses the secretion of acetylcholine at the distal end of the sympathetic nerve distributed in the sweat glands. Botox is injected into the affected area by injection, and thus, there is a difficulty in adjusting the depth of administration that must be administered to a depth within 2 mm, as well as side effects such as injection pain and muscle paralysis. Accordingly, in recent years, various studies have been continuously conducted to effectively treat hyperhidrosis while reducing treatment pain to the affected area.

Korean Registered Patent No. 1747411 Korean Registered Patent No. 1785930

An object of the present invention is to provide a micro-needle patch for the treatment of hyperhidrosis that can be applied evenly to the affected area where hyperhidrosis treatment is required and can be administered in a quantitative amount and reduce treatment pain.

Another object of the present invention is to provide a method of manufacturing a microneedle patch for the treatment of hyperhidrosis to produce a microneedle for achieving the above object.

The microneedle patch according to the present invention for achieving the above object includes a plurality of needle portions penetrating the chemical solution containing the active ingredient into the skin and a base portion that simultaneously supports the plurality of needle portions and adheres to the skin. Active ingredients include botulinum toxin.

In addition, a stabilizer for stabilizing the botulinum toxin may be added to the chemical solution.

In addition, the needle portion may include a needle body having a pointed tip (Tip) shape and a coating layer coated with the chemical solution on the needle body, and may be solidified by being dried after the coating layer is coated on the needle body.

In addition, the needle body may have a height of 800 μm or more, and a tensile modulus of 2.5 GPa or more and a tensile strength of 50 MPa or more.

Further, the coating layer is prepared by coating the needle body at least once in a coating solution corresponding to the chemical solution (Dip coating), and a thickening agent for increasing coating viscosity may be added to the coating solution.

In addition, a plurality of needle portions are provided to be spaced apart from each other at a distance of 1 mm or more, and the base portion may be adjustable in area in correspondence with the number of needle portions.

In addition, a plurality of the base portion is provided to have a partitioned shape based on a sweat gland-free node and wrinkles, and the needle portion may be supported on the base portion in a number corresponding to the area of the plurality of partitioned base portions.

The method for manufacturing a microneedle patch according to an exemplary embodiment of the present invention comprises the steps of providing a plurality of needle portions for penetrating a chemical solution containing botulinum toxin into the skin and supporting the plurality of needle portions to the skin It includes a step of providing a base portion to be in close contact, the base portion is adjustable in area corresponding to the number of the needle portion.

In addition, the needle portion preparation step includes a molding step of providing a needle body having a pointed tip (Tip) shape in a molding method and a coating step of coating the chemical solution on the outer surface of the needle body, the coating step The botulinum toxin, a stabilizer for stabilizing the botulinum toxin, and a thickener to increase the coating viscosity may be coated by dipping (Dip coating) to immerse the needle body multiple times.

In addition, the molding step, the step of providing a mold having a mold groove corresponding to the needle body, poly-lactic acid (PLA, poly-lactic-acid), poly-lactic acid (L-PLA, poly-) in the mold Supply biodegradable polymer containing at least one of L-lactic-acid (PGA), poly-glycolic-acid (PGA), and poly-lactic-co-glycolic acid (PLGA) to the mold The method comprising: heating the mold supplied with the biodegradable polymer to melt the polymer material, and then reducing the pressure; and cooling the mold to separate the needle body from the mold groove, wherein the separated needle body It can be treated with ultraviolet (UV) and ozone (Ozone).

In addition, the needle body may have a height of 800 μm or more, and a tensile modulus of 2.5 GPa or more and a tensile strength of 50 MPa or more.

In addition, the coating layer may be coated from the end of the needle body to 4/5 of the entire length.

In addition, a plurality of the base portions are provided to have a partitioned shape based on the no glands and wrinkles without sweat glands, and the needle portions are spaced apart from each other by an interval of 1 mm or more, and the base portion in a number corresponding to the area of the plurality of the base portions Can be supported.

According to the present invention having the configuration as described above, first, by infiltrating a plurality of needles provided with a medicinal solution containing botulinum toxin and infiltrating the affected area having the same area as the palm, it is possible to quantitatively supply the medicinal solution for hyperhidrosis treatment.

Second, by controlling the number of needle portions in correspondence to the region where hyperhidrosis is formed, a fixed amount of drug can be evenly penetrated into the entire area of the affected area, thereby improving treatment efficiency.

Third, compared to the conventional injection method, it is possible to reduce pain and fear when penetrating botulinum toxin, thereby providing excellent treatment accessibility.

Fourth, it is possible to supply botulinum toxin only to the subcutaneous layer, thereby improving problems such as muscle paralysis and long-term degeneration of the conventional injection method, which is difficult to control the depth of penetration.

Fifth, it is possible to improve treatment stability by adding a stabilizer capable of stabilizing botulinum toxin.

1 is a view schematically showing various forms according to the palm shape of the microneedle patch for the treatment of hyperhidrosis according to one preferred embodiment of the present invention.
FIG. 2 is a cross-sectional view schematically excerpting a portion of the microneedle patch shown in FIG. 1.
3 is an image schematically photographing the microneedle patch shown in FIG. 1 with a scanning electron microscope (SEM).
4 is a graph of the stability test results according to the composition of the microneedle patch shown in FIG. 1. And,
5 is an image schematically comparing the results of an in-vivo experiment using the microneedle patch shown in FIG. 1.

Hereinafter, a preferred embodiment of the present invention will be described with reference to the accompanying drawings.

1, the micro-needle patch 1 according to an exemplary embodiment of the present invention includes a needle portion 10 and a base portion 20.

Needle portion 10 is provided with a plurality that can penetrate the skin. The needle part 10 includes a needle body 10a having a tip-shaped tip, and a coating layer 10b coated on the outer surface of the needle body 10b, as shown in FIG. 2.

The needle body 10a has an approximately square horn shape and may be formed of a biodegradable polymer. Here, the biodegradable polymer is poly-lactic acid (PLA, poly-lactic-acid), poly-lactic acid (L-PLA, poly-L-lactic-acid), polyglycolic acid (PGA, poly-glycolic-acid), It may include at least one of poly-lactic-co-glycolic acid (PLGA). The needle body 10a formed of such a biodegradable polymer has a height of approximately 800 μm or more, a tensile modulus of 2.5 GPa or more, and a tensile strength of 50 MPa or more, thereby relating to sweat glands. It is good that only the subcutaneous layer of the skin where the nerve is provided can penetrate.

The coating layer 10b is coated with a chemical solution on the outer surface of the needle body 10a. The coating layer 10b may be coated by a dip coating method in which a needle body 10a is immersed in a chemical liquid after preparing a coating liquid containing the chemical liquid.

On the other hand, the drug solution contains an active ingredient, and in this embodiment, it contains botulinum toxin to be applied to the treatment of hyperhidrosis. In addition, a stabilizer for stabilizing botulinum toxin may be added to the chemical solution. In addition, a thickener may be included in the coating solution containing the chemical solution, and in this embodiment, the thickener is illustrated as including a CMC (carboxymethyl-cellulose sodium salt) material. For reference, the CMC thickener increases the coating viscosity of the coating layer 10b and induces that the chemical solution does not flow on the outer surface of the needle body 10a to be coated.

Meanwhile, in the present embodiment, the coating solution is illustrated as being prepared by mixing at a ratio of 7% (w/w) of CMC as a thickener and 0.0003% (w/w) of botulinum toxin. The mixing ratio of botulinum toxin and thickener is only an example, and is not limited thereto.

In addition, the needle body 10a may be immersed in a coating solution multiple times at a predetermined time interval to be coated. In this embodiment, the needle body 10a is illustrated as being immersed in a coating solution three times at 15 minute intervals. In this way, the needle portion 10 is solidified by being dried after the coating layer 10b is coated on the outer surface of the needle body 10a by immersing the coating solution containing the chemical liquid multiple times.

For reference, it is preferable that the coating layer 10b is coated up to about 4/5 point from the end having a pointed tip shape with respect to the entire length of the needle body 10a. By coating the coating layer 10b with a sufficient coating area on the outer surface of the needle body 10a, botulinum toxin, an active ingredient of the coating layer 10b, can sufficiently penetrate the subcutaneous layer of the skin.

The base portion 20 has an area to support the plurality of needle portions 10 at the same time to be in close contact with the skin. The base portion 20 supports a plurality of needle portions 10 spaced apart from each other in multiple rows and multiple rows at the same time, and has a type of patch for evenly penetrating the needle portion 10 into the affected portion. Therefore, the base portion 20 is good to have a flexible property to be in close contact with the curved skin in a state in which the plurality of needle portions 10 are supported. At this time, the base portion 20 is preferably a plurality of needle portions 10 spaced apart from each other in multiple rows and multiple rows at intervals of approximately 1 mm or more.

In addition, as shown in FIG. 1, the base portion 20 may have an area adjusted to correspond to an area of the skin to be administered. That is, the number of needle portions 10 may be adjusted corresponding to the area of the affected area of the skin, and the area of the base portion 20 may also be adjusted corresponding to the number of needle portions 10.

More specifically, as shown in FIG. 1, the treatment of hyperhidrosis is unnecessary because there is no sweat gland in the wrinkles of the finger joints, based on the palm, which requires treatment of hyperhidrosis. Accordingly, the area of the base portion 20 can be adjusted by dividing the section into finger joints and corresponding area. In the figure of FIG. 1, the number displayed for each compartment on the palm refers to the number of needle portions 10 supported on one base portion 20.

Referring to FIG. 1 in more detail, assuming that the plurality of needle portions 10 are spaced apart from each other at a row spacing d1 of approximately 5 mm and spaced at a column spacing h1 of approximately 7 mm, each node of the finger is approximately 9 15 to 15 needle portions 10 are supported on the base portion 20. In addition, approximately 12 to 35 needle portions 10 may be supported on the base portion 20 so that the upper portion of the palm corresponds to the partition divided along the wrinkles of the fingerprint.

At this time, in the illustration of FIG. 1, corresponding to the upper portion of the palm, 35 needle portions 10 spaced apart from each other by a row spacing d2 and a column spacing h2 of 5 mm are supported by the base portion 20, and 27 The needle portion 10 is illustrated as being divided into two so as to be supported by the base portion 20, but is not limited thereto. That is, 20, 15, 12, and 15 needle portions 10 are supported on the four base portions 20 so as to be partitioned, respectively, and a modified example that penetrates into the upper portion of the palm is also possible.

In addition, the upper portion of the palm is divided into two or four base portions 20 so that a plurality of needle portions 10 do not penetrate, and a plurality of needle portions 10 are supported on one base portion 20, Various modifications are possible, such as the needle portion 10 being supported such that it is divided into five or more base portions 20.

In addition, although the shape of the needle part 10 supported by the base part 20 corresponding to the lower part of the palm is not illustrated, approximately 64 to 88 needle parts 10 each have one or two or more base parts 20. It can be divided into a variety of forms that can be supported. In addition, although not shown in detail, a modification example in which a total of about 150 needle portions 10 are supported by a base portion 20 of the lower portion of the palm is possible.

As described above, the base portion 20 of the microneedle patch 1 divides the plurality of needle portions 10 by dividing the palms into a plurality of portions based on areas where the sweat glands are not distributed, such as the finger joints of the palms and wrinkles of the palms. It can support and penetrate. Therefore, the microneedle patch 1 can be applied by adjusting the number of needle portions 10 in response to only the affected area where hyperhidrosis treatment is required, and the microneedle patch 1 of various areas can be applied in response to various palm sizes. It can be selectively applied.

The number of needle portions 10 for each compartment of the palm is not limited to the example illustrated in FIG. 1, and can be variously modified within a range in which more than 120 needle portions 10 are applied to the entire palm. In addition, this embodiment does not apply only to the palm, as shown in Figure 1, it is natural that it can be applied to various hyperhidrosis affected areas such as the soles, armpits, and the like.

When explaining the manufacturing method of the micro-needle patch 1 according to the present invention having the above configuration is as follows.

First, a needle portion 10 for infiltrating a chemical solution containing botulinum toxin is prepared. The needle part 10 preparation step has a molding step of providing the needle body 10a in a molding manner, and a coating step of coating the coating layer 10b on the surface of the provided needle body 10a.

The molding step, after preparing a mold having a molding groove corresponding to the needle body (10a), supplies a polymer material of at least one of the biodegradable polymer described above to the mold. Thereafter, the mold supplied with the polymer material is moved to the inside of the oven in a vacuum state to melt the polymer material by heat, and the pressure is reduced to a predetermined pressure. Then, the polymer material is filled in the mold groove of the mold.

When the mold groove is filled with the polymer material, the mold is cooled at room temperature to solidify it. Thereafter, by separating the solidified polymer material provided in the mold groove of the mold, the manufacturing of the needle body 10a is completed. At this time, the needle body 10a separated from the mold may be moved to the inside of a device to which ultraviolet (UV) and ozone (Ozone) are supplied, and the surface of the needle body 10a may be treated with ultraviolet light and ozone for a predetermined time.

In the coating step, the needle body 10a provided by molding is immersed in a coating solution containing a chemical solution to be coated. At this time, the coating solution may include botulinum toxin, a stabilizer, a thickener, and pure water, as described above, and the needle body 10a is immersed 3 times in 15 minutes intervals to be coated in the coating solution to coat the needle body 10a with a coating layer. (10b) is coated.

When the needle part 10 is provided, the microneedle patch 1 is finally manufactured through a support step in which the base part 20 simultaneously supports the plurality of needle parts 10. At this time, the area of the base portion 20, the number of needle portions 10 supported on the base portion 20, etc., refer to the illustration of FIG. 1, but FIG. 1 is not limited to the illustration.

As described above, an image obtained by scanning a microneedle patch 1 including a plurality of needle portions 10 supported on the base portion 20 with a scanning electron microscope (SEM) is illustrated in FIG. 3. As shown in FIG. 3, a plurality of needle portions 10 are arranged in a row and a row in the base portion 20 having a predetermined area with a sharp tip shape.

On the other hand, Figure 4, a graph comparing the composition of the stabilizer for stabilizing botulinum toxin added to the chemical solution is shown. Referring to FIG. 4, F1, F2, and F3 differ in the degree of stability of botulinum toxin according to differences in excipients, ie, surfactants or stabilizers, added to the chemical solution. The composition ratios of F1, F2 and F3 are shown in Table 1 below.

Here, BTA is botulinum toxin, CMC is a thickener, Tween 80 is a surfactant, HSA is albumin used as a stabilizer (Human Serum Albumin, HSA), and DI water is pure. When comparing the drug solution mixed in the ratio shown in Table 1, it can be seen that the best stability is obtained under the formulation conditions of F1 in which only stabilizers are added to botulinum toxin.

For reference, albumin has a property having effective stability against toxin during freeze drying, and thus is effective in stabilizing botulinum toxin during the process of coating and drying the coating layer 10b on the needle body 10a at room temperature. Able to know. Accordingly, in this embodiment, it is illustrated that the composition of the coating solution including the chemical solution for forming the coating layer 10b is based on the F1 composition of Table 1.

5 shows an image of a result of experimenting on an animal using the microneedle patch 1 having the needle part 10 and the base part 20 described above. (A) of FIG. 5 is an image applied by botulinum toxin by injection, and (b) is an image of applying the microneedle patch 1 according to the present invention including botulinum toxin composed of the composition F1 of Table 1.

5 (a) and (b), as a result of comparing the sweating response (sweating response) in the foot pad of the animal, (b) is applied to the microneedle patch (1) according to the invention containing botulinum toxin It can be seen that the sweating reaction was relatively reduced compared to the conventional (a). Accordingly, it can be confirmed that the microneedle patch 1 according to the present invention quantitatively penetrated botulinum toxin evenly over the entire area of the affected area and delivered it to the subcutaneous layer of the skin.

As described above, although described with reference to preferred embodiments of the present invention, those skilled in the art variously modify and change the present invention without departing from the spirit and scope of the present invention as set forth in the claims below. You can understand that you can.

1: Micro needle patch 10: Needle part
10a: needle body 10b: coating layer
20: base

Claims (13)

A plurality of needle portions penetrating the chemical solution containing the active ingredient into the skin; And
A base portion supporting the plurality of needle portions at the same time and in close contact with the skin;
It includes,
The active ingredient is a micro needle patch containing botulinum toxin (botulinum toxin). According to claim 1,
The chemical solution is a microneedle patch to which a stabilizer that stabilizes the botulinum toxin is added. According to claim 1,
The needle portion,
A needle body having a tip-shaped tip; And
A coating layer coated with the chemical solution on the needle body;
It includes,
The microneedle patch that solidifies by drying after the coating layer is coated on the needle body. According to claim 3,
The needle body has a height of 800 µm or more, a tensile elastic modulus of 2.5 GPa or more, and a micro needle patch having a mechanical strength of 50 MPa or more. According to claim 3,
The coating layer is prepared by coating the needle body at least once in a coating solution corresponding to the chemical solution (Dip coating),
Microneedle patch is added to the coating solution to increase the viscosity of the coating. According to claim 1,
The needle portion is provided with a plurality of spaced apart from each other at a distance of 1mm or more,
The base portion is a micro-needle patch with an adjustable area corresponding to the number of needle portions. According to claim 1,
A plurality of the base portion is provided to have a partitioned shape based on nodes and wrinkles without sweat glands,
The needle portion is a micro-needle patch supported on the base portion in a number corresponding to the area of the plurality of partitioned base portion. Providing a plurality of needle portions for penetrating the chemical solution containing botulinum toxin into the skin; And
Providing a base portion for supporting the plurality of needle portions and in close contact with the skin;
It includes,
The base portion manufacturing method of the micro-needle patch with an adjustable area in accordance with the number of the needle portion. The method of claim 8,
The needle portion preparation step,
A molding step of providing a needle body having a tip-shaped tip in a molding manner; And
A coating step of coating the chemical solution on the outer surface of the needle body;
It includes,
The coating step is a botulinum toxin, a method for manufacturing a microneedle patch coated with a dip coating method in which the needle body is dipped multiple times in a coating solution to which a stabilizer for stabilizing the botulinum toxin and a thickener for increasing coating viscosity are added. The method of claim 9,
The molding step,
Providing a mold having a mold groove corresponding to the needle body;
Polylactic acid (PLA, poly-lactic-acid), poly-lactic acid (L-PLA, poly-L-lactic-acid), polyglycolic acid (PGA), polylactic acid in the mold Supplying a biodegradable polymer comprising at least one of poly-lactic-co-glycolic acid (PLGA) to the mold;
Heating the mold supplied with the biodegradable polymer to melt the polymer material and then reducing the pressure; And
Cooling the mold to separate the needle body from the mold groove;
It includes,
The separated needle body is a method of manufacturing a micro needle patch treated with ultraviolet (UV) and ozone (Ozone). The method of claim 9,
The needle body has a height of 800㎛ or more, the method of manufacturing a micro-needle patch having a tensile modulus of 2.5GPa or more, a tensile strength of 50MPa or more mechanical strength. The method of claim 9,
The coating layer is a method of manufacturing a micro needle patch is coated from the end of the needle body to 4/5 points of the entire length. The method of claim 8,
A plurality of the base portion is provided to have a partitioned shape based on nodes and wrinkles without sweat glands,
The needle portion is spaced apart from each other at a distance of 1mm or more, a method of manufacturing a micro needle patch supported on the base portion in a number corresponding to the area of the plurality of the base portion.

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