WO2025174199A1 - Composition for microneedle, and microneedle using same - Google Patents

Abstract

A composition for a microneedle and a microneedle using same are disclosed. The composition for a microneedle according to an embodiment of the present invention comprises sodium hyaluronate and hydroxypropyl methylcellulose (HPMC).

Description

Composition for microneedles and microneedles using the same

The present invention relates to a composition for microneedles and a microneedle using the same, and more particularly, to a composition for microneedles and a microneedle using the same, which can stably maintain a formulation by increasing the storage time of microneedles and the strength retention time of a formulation using hydroxypropyl methylcellulose, which increases moisture stability.

Microneedles are tiny needles that pierce tiny holes in the skin to deliver drugs, vaccines, cosmetic ingredients, etc. Compared to conventional injection needles, they cause less pain, have high penetrability, and are easy to self-administer, so they are used in various fields.

Microneedles can directly act on the skin's surface, i.e., the dermis or transdermis, by using their formulation, and thus can have effects such as wrinkle improvement, whitening, skin moisturizing, and skin nutrition.

In order to achieve the above effects, the microneedle or the active ingredient within the microneedle is immediately dissolved in the injected skin and is sufficiently absorbed, which increases the efficacy, and hydrophilic ingredients with this property are mainly used.

Specifically, microneedles come in two types: biodegradable and soluble. Biodegradable microneedles are made from biodegradable materials such as PDO (Polydioxanone), PLLA (Poly-L-Lactic Acid), and PCL (Polycaprolactone). After being inserted into the skin, they naturally decompose over a long period of time (from several weeks to several months) and are absorbed into the body.

On the other hand, soluble microneedles are made of hyaluronic acid, collagen, peptides, gelatin, etc., and after being inserted or attached to the skin, they dissolve in the skin within a short period of time (minutes to hours) compared to biodegradable types, releasing the drug.

These soluble microneedles are made of hydrophilic materials (hereinafter referred to as soluble materials) so that they dissolve immediately in the skin and are sufficiently absorbed, thereby exhibiting high efficacy.

Meanwhile, moisture stability refers to the ability of a composition to maintain stable physical or chemical properties without change when exposed to moisture, such as water or water vapor. In other words, a composition for microneedles with improved moisture stability can increase the time it takes for the microneedles to maintain their mechanical strength.

Conventional microneedles use hydrophilic ingredients that dissolve quickly to enable rapid drug injection and high efficacy when used, but they have the problem of short shelf life and difficulty in storage due to unstable moisture stability.

The purpose of the present invention is to solve such conventional problems, and to provide a composition for microneedles and a microneedle using the same, which increases the moisture stability of the microneedles by using sodium hyaluronate and hydroxypropyl methylcellulose, thereby prolonging the formulation retention time and facilitating storage.

The tasks of the present invention are not limited to the tasks mentioned above, and other tasks not mentioned will be clearly understood by those skilled in the art from the description below.

In order to solve the above-described problem, a composition for microneedles according to one aspect of the present invention includes sodium hyaluronate and hydroxypropyl methylcellulose (HPMC).

It may contain sodium hyaluronate and hydroxypropyl methylcellulose in a ratio of 1:(0.1 to 5).

Further comprising a plasticizer, wherein the plasticizer may include one or more of polyethylene glycol (PEG), glycerol, propylene glycol, sorbitol, triacetin, triethyl citrate, dibutyl phthalate, diethyl phthalate, polypropylene glycol, lanolin, castor oil, dibutyl sebacate, citrate esters, glyceryl tricaprylate, and dimethyl adipate.

Further comprising a biodegradable material, wherein the biodegradable material may include one or more of polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), carbomer, alginate, gelatin, methylcellulose (MC), hydroxypropyl cellulose (HPC), chitosan, polyacrylic acid, acrylate copolymers, dextran, and trehalose.

The functional material may further include at least one selected from the group consisting of niacinamide, madecassoside, Centella Asiatica Extract, salicylic acid, Salix Alba (Willow) Bark Extract, or water.

Microneedles according to another aspect of the present invention can be manufactured using the composition for microneedles described above.

According to the composition for microneedles of the present invention and microneedles using the same, one or more of the following effects are achieved.

The composition for microneedles according to the present invention and the microneedles using the same have the effect of increasing moisture resistance (moisture stability) to maintain the strength and formulation of the microneedles for a long time, and preventing deformation due to environmental changes such as humidity and temperature, thereby increasing the stable storage time.

The effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description of the claims.

Figure 1 is a table showing a formulation example of a composition for microneedles according to an embodiment of the present invention.

Figure 2 is a table showing the results of a physical property evaluation test according to the mixing ratio of Figure 1.

Figure 3 is an enlarged image of a microneedle immediately after manufacturing using combinations 1 and 2 from the table in Figure 2.

Figure 4 is an enlarged image of the microneedle of Figure 3 after being stored for 24 hours under high humidity conditions.

Figure 5 is an enlarged image of the microneedle of Figure 3 after being stored for 96 hours under high humidity conditions.

Figure 6 is a flowchart showing a method for manufacturing microneedles using a composition for microneedles according to an embodiment of the present invention.

The advantages and features of the present invention, and the methods for achieving them, will become clearer with reference to the embodiments described in detail below together with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below and may be implemented in various different forms. These embodiments are provided only to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims. Like reference numerals designate like elements throughout the specification.

The sizes and shapes of components depicted in the drawings attached to this specification may be exaggerated for clarity and convenience of explanation. It should be noted that identical components are sometimes depicted with the same reference numerals in each drawing. Furthermore, detailed descriptions of functions and structures of known technologies that may unnecessarily obscure the gist of the present invention may be omitted.

The terminology used herein is used to describe specific embodiments and is not intended to limit the present invention. As used herein, the singular form may include the plural form unless the context clearly dictates otherwise. Furthermore, whenever a part of this specification is referred to as "comprising" a component, this means that it may also include other components, unless otherwise specifically stated.

When a component is referred to as being "connected" or "connected" to another component, it should be understood that it may be directly connected or connected to that other component, but that there may be other components in between. Conversely, when a component is referred to as being "directly connected" or "connected" to another component, it should be understood that there are no other components in between. Other expressions used to describe the relationship between components should be interpreted similarly.

The terms "top," "bottom," "upper surface," "lower surface," or "upper" and "lower surface" as used herein are used to distinguish the relative positions of components. For example, for convenience, the upper surface in a drawing may be referred to as "upper surface" and the lower surface in the drawing as "lower surface." In practice, the upper surface may be referred to as "lower surface" and the lower surface as "upper surface" without departing from the scope of the present invention.

Terms containing ordinal numbers, such as "first," "second," etc., described herein may be used to describe various components; however, these components are not limited by these terms. These terms are merely used to distinguish each component from another, and are not limited by the manufacturing order. Furthermore, the names may not be consistent between the detailed description of the invention and the claims.

All terms, including technical or scientific terms, used herein, unless otherwise defined, have the same meaning as commonly understood by those of ordinary skill in the art to which this invention pertains. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and shall not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

Hereinafter, embodiments of the present invention will be described with reference to the attached drawings.

Figure 1 is a table showing a formulation example of a composition for microneedles according to an embodiment of the present invention.

A composition for microneedles according to an embodiment of the present invention comprises sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) (HPMC).

Sodium hyaluronate (100) is a component that can retain moisture and can be used as a moisturizer for purposes such as improving wrinkles and preventing aging, and is the main ingredient in artificial tears.

Sodium hyaluronate (100) can only replenish moisture to the cornea, so it can be used regardless of the patient's severity and condition.

Hydroxypropyl methylcellulose (200) is also known as hydroxypropyl methylcellulose, hypromellose, or hypromellose.

Hydroxypropyl methylcellulose (200) is a biodegradable polymer compound that can be used as a drug delivery vehicle or as a coating agent. For example, hydroxypropyl methylcellulose (200) can be used as a semi-synthetic agent used as an additive in foods, pharmaceuticals, and cosmetics.

Hydroxypropyl methylcellulose (200) can be used to compensate for the difficulty in long-term storage due to the characteristics of microneedles that must be rapidly dissolved and administered to the skin, and can prolong the shelf life of the formulation by increasing moisture stability.

The composition for microneedles according to an embodiment of the present invention includes hydroxypropyl methylcellulose (200) together with sodium hyaluronate (100), thereby delaying the dissolution rate of the microneedles, thereby increasing the retention time of strength, and consequently, facilitating the storage of the microneedles.

Referring to FIG. 1, combination 1 (300) represents a case in which a composition for microneedles includes sodium hyaluronate (100) but does not include hydroxypropyl methylcellulose (200).

A composition for microneedles according to an embodiment of the present invention may include sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) in a ratio of 1:(0.1 to 5) as shown in formulation 2 (400).

Conventional soluble microneedles have a problem in that their storage stability is reduced because they absorb moisture in a high-humidity environment, making it difficult for the needles to maintain their shape and melt.

According to an embodiment of the present invention, when sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) are mixed in a ratio of 1:(0.1 to 5) to manufacture soluble microneedles, the microneedles can be prevented from melting and losing their shape due to moisture in the air while maintaining their dissolution properties in the body.

Sodium hyaluronate (100) is a biodegradable polymer and a major component of microneedle structures. Soluble microneedles composed of sodium hyaluronate (100) without hydroxypropyl methylcellulose (200) rapidly dissolve in the body, but are vulnerable to storage stability in humid environments due to their high hygroscopicity.

Hydroxypropyl methylcellulose (200) is a biodegradable and biocompatible polymer that is stable against humidity. When hydroxypropyl methylcellulose (200) is included in the manufacture of soluble microneedles, it can prevent drug dissolution and degradation due to humidity or moisture.

When the mixing ratio of sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) is set to 1: (0.1 to 5), the microneedle shape is maintained stably without collapsing even in a high-humidity environment.

The composition for microneedles according to an embodiment of the present invention may further include glycerin and water together with the above-described sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) to increase the moisture stability of the microneedles.

At this time, sodium hyaluronate (100) can be mixed in a weight ratio of 1% to 50%, hydroxypropyl methylcellulose (200) in a weight ratio of 3% to 10%, glycerin in a weight ratio of 0.5% to 5%, and water in a weight ratio of 35% to 95.5%.

Microneedles manufactured using sodium hyaluronate (100) may break after drying or have difficulty maintaining an even shape when sodium hyaluronate (100) is used alone, so glycerin may be added to provide flexibility.

Glycerin content Whether the shape is maintained or not less than 0.5% difficulty 0.5% Maintainable 3% Maintainable 5% Maintainable 6% difficulty

Referring to [Table 1] above, when the glycerin content was less than 0.5%, the microneedles were prone to breaking due to the lack of glycerin. When the glycerin content was 0.5%, the shape of the microneedles could be maintained even with the minimum glycerin content, and when the glycerin content was 3%, the elasticity and strength of the microneedles could be maintained with the appropriate glycerin content. When the glycerin content was 5%, there was no problem in maintaining the shape of the microneedles even with the maximum allowable glycerin content. When the glycerin content was 6% or more, it was sticky and hygroscopic, making sheet formation difficult. Therefore, in the embodiment of the present invention, it was found that the shape of the microneedles could be normally maintained when the glycerin content was in the range of 0.5% to 5%.

At this time, due to the high moisture content, if the microneedles are exposed to the air, they may melt due to water vapor and have difficulty maintaining their shape. To solve this problem, in the embodiment of the present invention, hydroxypropyl methylcellulose (200) was added, and when mixed in the above-described weight ratio, it was confirmed that the structure of the microneedles was maintained in an optimal state even in a high-humidity environment, effectively securing moisture stability.

Meanwhile, the composition for microneedles according to an embodiment of the present invention may further include various plasticizers in addition to the above-described glycerin.

Plasticizers can be used to increase the flexibility of polymer compositions and facilitate microneedle formation.

The plasticizer may include one or more of polyethylene glycol (PEG), glycerol, propylene glycol, sorbitol, triacetin, triethyl citrate, dibutyl phthalate, diethyl phthalate, polypropylene glycol, lanolin, castor oil, dibutyl sebacate, citrate esters, glyceryl tricaprylate, and dimethyl adipate.

In another example, a composition for microneedles according to an embodiment of the present invention may further include a biodegradable material.

The biodegradable material may include one or more of polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), carbomer, alginate, gelatin, methylcellulose (MC), hydroxypropyl cellulose (HPC), chitosan, polyacrylic acid, acrylate copolymers, dextran, and trehalose.

In another example, a composition for microneedles according to an embodiment of the present invention may further include a functional material, wherein the functional material may include at least one selected from the group consisting of niacinamide, madecassoside, Centella Asiatica Extract, salicylic acid, Salix Alba (Willow) Bark Extract, or water.

Here, niacinamide has skin-protecting and soothing effects, whitening, and strengthening the skin barrier. Madecassoside is an ingredient that helps soothe the skin, reduce inflammation, and aid in wound healing, and is used to promote wound healing. Centella asiatica extract is an ingredient that helps soothe, reduce inflammation, and regenerate the skin, and is effective in wound healing and skin protection. Salicylic acid is primarily used to remove sebum and unclog pores, keeping the skin smooth. Willow bark extract is a natural form of salicylic acid that helps soothe skin by reducing skin irritation and providing anti-inflammatory and antibacterial properties.

The composition for microneedles according to an embodiment of the present invention may include various ingredients such as a solubilizer, a surfactant, a preservative, and an anti-inflammatory agent according to the intended use.

Fig. 2 is a table showing the results of a physical property evaluation test according to the mixing ratio of Fig. 1. Fig. 3 is an enlarged image of a microneedle immediately after manufacturing using mixing ratios 1 and 2 from the table of Fig. 2.

Referring to Fig. 2, the microneedle strengths according to combination 1 (300) and combination 2 (400) were 18.08 N and 24.30 N, respectively.

Combination 1 (300) represents a case in which the composition for microneedles includes sodium hyaluronate (100) as described above, but does not include hydroxypropyl methylcellulose (200).

Combination 2 (400) represents a composition for microneedles according to an embodiment of the present invention, which comprises sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) in a ratio of 1:(0.1 to 5).

The lengths of the microneedles immediately after manufacturing according to combination 1 (300) and combination 2 (400) were approximately 283 ㎛ and 272 ㎛, respectively.

The length of each microneedle according to combination 1 (300) and combination 2 (400) was measured immediately after manufacturing to evaluate whether the shape was maintained.

As illustrated in Fig. 3, there was no significant difference immediately after manufacture between the first microneedle (301) manufactured based on combination 1 (300) and the second microneedle (401) manufactured based on combination 2 (400). The microneedle may include a soluble microneedle.

Referring to the table illustrated in Fig. 2, the solubility in the body can be assessed by attaching the microneedles to human skin (e.g., forehead area) for 30 minutes, then removing them and measuring the reduced length. As a result of evaluating the solubility using this method, it was confirmed that the microneedles manufactured based on Formulation 2 (400) containing hydroxypropyl methylcellulose (200) were sufficiently dissolved in the body within 30 minutes.

Additionally, to eliminate differences in skin moisture content, solubility can be assessed by immersing the microneedles in a buffer solution (PBS) similar to body fluid for 2 seconds and measuring the reduced length. The results of this solubility assessment confirmed that the microneedles manufactured based on formulation 2 (400) exhibited sufficient solubility.

In addition, the length reduction rate of the microneedle under high humidity conditions was measured to evaluate whether the shape was maintained. As a result, it was found that when the content of hydroxypropyl methylcellulose (200) was contained at an appropriate ratio, the length reduction rate was reduced to approximately 4.4%, which significantly improved the moisture stability.

The solubility and moisture stability length reduction rate (%) can be defined as in the above [Mathematical Formula 1]. That is, the solubility and moisture stability length reduction rate (%) can be calculated by dividing the value obtained by subtracting the microneedle length before the test from the microneedle length after the test by the microneedle length before the test, and multiplying this value by 100 (%).

Figure 4 is an enlarged image of the microneedle of Figure 3 after being stored for 24 hours under high-humidity conditions, and Figure 5 is an enlarged image of the microneedle of Figure 3 after being stored for 96 hours under high-humidity conditions.

Figures 4 and 5 (a) show the appearance of the first microneedle (301) to which the composition 1 (300) was applied after storage for 24 hours and 96 hours under high humidity conditions, and the shape was not maintained for the most part.

On the other hand, (b) of FIGS. 4 and 5 shows the appearance of the second microneedle (401) to which the composition 2 (400) according to the embodiment of the present invention is applied after storage for 24 hours and 96 hours under high humidity conditions, and most of the original shape and structural stability are maintained.

In this way, the composition for microneedles including sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) according to an embodiment of the present invention can increase the durability against moisture (moisture stability) and thereby increase the strength of the microneedles and the retention time of the formulation.

Figure 6 is a flowchart showing a method for manufacturing microneedles using a composition for microneedles according to an embodiment of the present invention.

Referring to Fig. 6, sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) are mixed with a solvent (distilled water) and stirred for a set period of time to prepare a mixed solution for manufacturing microneedles (S601).

Here, sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) can be mixed with a solvent (distilled water) and stirred for more than 1 hour (rpm 6000 or more) to create an optimal mixed solution for manufacturing microneedles.

The mixed solution may further include one or more of the plasticizers, biodegradable materials and functional materials described above in other examples.

Sodium hyaluronate (100) and hydroxypropyl methylcellulose (200) can be mixed in a ratio of 1:(0.1 to 5). This prevents the microneedles manufactured from collapsing due to moisture in the air and from melting, while maintaining their dissolution properties in the body.

Next, the above-described mixed solution is applied to a mold in which a microneedle negative shape is formed, and then vacuum treatment is performed using a vacuum chamber (S611).

The pressure inside the vacuum chamber can be maintained at a set pressure lower than atmospheric pressure for a set period of time. By performing the vacuum treatment process in this manner, the mixed solution for microneedle manufacturing can be effectively filled up to the tip (also called the tip) of the negative portion of the mold.

In another example, before applying the above-described mixed solution to the mold, a vacuum treatment may first be performed by a vacuum chamber, and then the mixed solution may be applied to the mold, and then the vacuum treatment process may be performed again on the mold to which the mixed solution has been applied.

By vacuum-treating the mold before applying the mixed solution (medicinal solution) to the mold in which the negative shape of the microneedle is formed, there is an effect of preventing air pockets or bubbles from occurring within the applied mixed solution.

In addition, by performing vacuum treatment again after the mixed solution is applied to the mold, residual air can be removed, effectively removing fine bubbles that may occur inside the mixed solution or at the contact surface with the mold.

Next, the mold to which the mixed solution has been applied is dried by a drying device (e.g., an oven) (S621).

Here, drying can be performed according to the conditions set in the drying device (e.g., temperature of 30°C to 70°C for more than 1 hour) to achieve optimal microneedle manufacturing.

Afterwards, the microneedles (sheets) are separated (detached) from the dried mold (S631).

In this way, by manufacturing microneedles using the composition for microneedles according to an embodiment of the present invention, it is possible to manufacture microneedles of excellent quality that can maintain dissolution properties in the body while preventing them from melting and losing their shape due to moisture in the air.

Although the preferred embodiments of the present invention have been illustrated and described with reference to the drawings as described above, the present invention is not limited to the specific embodiments described above, and various modifications may be made by a person skilled in the art to which the invention pertains without departing from the gist of the present invention as claimed in the claims. Furthermore, such modifications should not be understood individually from the technical idea or prospect of the present invention.

The present invention relates to a composition for microneedles and microneedles using the same, and can be used in industries such as the health care industry.

Claims (5)

Sodium Hyaluronate; and A composition for microneedles, characterized by comprising hydroxypropyl methylcellulose (HPMC). In the first paragraph, Including more plasticizers, The above plasticizer is, A composition for microneedles comprising at least one of polyethylene glycol (PEG), glycerol, propylene glycol, sorbitol, triacetin, triethyl citrate, dibutyl phthalate, diethyl phthalate, polypropylene glycol, lanolin, castor oil, dibutyl sebacate, citrate esters, glyceryl tricaprylate, and dimethyl adipate. In the first paragraph, Including further biodegradable materials, The above biodegradable material is, A composition for microneedles comprising at least one of polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), carbomer, alginate, gelatin, methylcellulose (MC), hydroxypropyl cellulose (HPC), chitosan, polyacrylic acid, acrylate copolymers, dextran, and trehalose. In the first paragraph, Including more functional substances, The above functional material is, A composition for microneedles further comprising at least one selected from the group consisting of niacinamide, madecassoside, Centella Asiatica Extract, salicylic acid, Salix Alba (Willow) Bark Extract, or water. A microneedle manufactured using a composition for microneedles according to any one of claims 1 to 4.