Allantoin microneedle crystals and cosmetic compositions comprising the same

Abstract

This invention relates to allantoin microneedle crystals, cosmetic compositions containing the same, and active ingredient delivery systems. According to one aspect of the invention, the allantoin microneedle crystals are made by crystallizing poorly soluble allantoin to achieve excellent solubility, making them suitable as a component of cosmetic compositions. These microneedle crystals have a needle-like morphology similar to that of needles with an average long axis length of 5 to 500 μm, allowing them to penetrate and be absorbed into the skin simply by application. Furthermore, they dissolve into the skin through rolling after application, exhibiting excellent safety. Even under harsh conditions, they remain stable and unchanged in properties, providing excellent storage and distribution advantages.

Description

Technical Field

[0001] This specification relates to allantoin microneedle crystals and cosmetic compositions containing them. Background Technology

[0002] In recent years, home-use skincare cosmetics employing "microneedling" technology, primarily used in dermatological cosmetic medical devices, have become increasingly popular. These cosmetics leverage the principles of dermatological treatments, providing a tingling and discomfort sensation, to deliver the effects achievable through dermatological procedures, thus establishing their selling point. The core ingredients of most microneedling-based home skincare cosmetics correspond to cosmetic ingredients such as Centella Asiatica extract contained in purified silica needles made from animal-derived materials. These microneedles act as a physical delivery system, physically promoting skin penetration without the need for separate devices, thereby stimulating consumer desire. Consumers can directly experience the active ingredients and it also aids in the absorption of other active ingredients.

[0003] However, the main component of these microneedles, spicules (hydrolyzed sponges), is made from animal-derived materials, has a sponge-like skeleton, and is composed of approximately 99% silica. Because these spicules are insoluble, they can cause excessive stinging on sensitive skin after application, and the needles can remain in the skin, causing persistent pain even over time.

[0004] Therefore, the inventors are dedicated to developing a new material that has the same morphology as microneedles, can penetrate the skin, produce effects similar to dermatological treatments, and can also dissolve within the skin, thereby overcoming the shortcomings of bone needles. This invention was born from this.

[0005] [Existing Technical Documents]

[0006] [Patent Documents]

[0007] (Patent Document 1) KR 10-2017-0000747 A

[0008] (Patent Document 2) JP 7416309 B1

[0009] (Patent Document 3) KR 10-1999-0063069 A

[0010] (Patent Document 4) KR 10-2024-0060951 A Summary of the Invention

[0011] Problems to be solved

[0012] The inventors are dedicated to developing a material that has the same morphology as microneedles, can penetrate the skin, produce effects similar to dermatological treatments, and can also dissolve within the skin. Research results have confirmed that precipitating amorphous allantoin into crystals with the same shape as microneedles can achieve the above-mentioned effects.

[0013] Therefore, on the one hand, the purpose of this invention is to provide a novel material that has the same morphology as microneedles, provides a dermatological treatment-like sensation to the user when applied to the skin, and is safe because it is soluble after penetrating the skin.

[0014] Problem Solving Methods

[0015] In one aspect, the present invention provides allantoin microneedle-like crystals having an average length of 5 to 500 μm for their long axis.

[0016] In another aspect, the present invention provides a cosmetic composition comprising allantoin microneedle crystals as an active ingredient.

[0017] Invention Effects

[0018] According to one aspect of the present invention, allantoin microneedle crystals are made by crystallizing poorly soluble allantoin to have excellent solubility, and can be used as a component of cosmetic compositions. The microneedle crystals have the same needle-like morphology as needles with an average length of 5 to 500 μm on the long axis, so that they can penetrate into the skin and be absorbed by the skin simply by applying them to the skin. Moreover, they dissolve into the skin by rolling after application, and have excellent safety. They remain stable and unchanged in properties even under harsh conditions, and have excellent effects in terms of easy storage and distribution. Attached Figure Description

[0019] Figure 1 This is a photograph of allantoin microneedle-like crystals according to an embodiment of the present invention.

[0020] Figure 2 This photo was taken when regular allantoin powder was dissolved in deionized water.

[0021] Figure 3 This is a photograph taken when allantoin microneedle crystals according to an embodiment of the present invention are dissolved in deionized water.

[0022] Figure 4a In an in vitro keratinocyte residue assessment experiment according to an embodiment of the present invention, a photograph of the cross-section of the untreated group after Nile red staining was taken.

[0023] Figure 4bIn an in vitro stratum corneum residue assessment experiment according to an embodiment of the present invention, a cross-sectional photograph of allantoin powder, which serves as a control group, was taken 18 hours after being applied to skin biopsy tissue.

[0024] Figure 4c In an in vitro stratum corneum residue assessment experiment according to an embodiment of the present invention, a cross-sectional photograph of allantoin microneedle crystals according to an embodiment of the present invention was taken 18 hours after being applied to skin biopsy tissue.

[0025] Figure 5 This is a graph illustrating the perceptual level of allantoin microneedle crystal content according to an embodiment of the present invention.

[0026] Figure 6 These are photographs taken to confirm the dosage form stability of allantoin microneedle crystals according to an embodiment of the present invention when stored under various conditions including room temperature (RT), refrigeration, 37°C, 45°C, and cycling (CYC). Detailed Implementation

[0027] In this specification, "needle-like" refers to a shape that is long and thin like a needle with a sharp end, "crystal" refers to a crystalline solid that does not contain solvent molecules in a substantially fixed molar ratio within its crystal lattice, i.e., a non-solvent crystalline solid, and "needle-shaped crystal" is a crystal with a pointer shape.

[0028] The present invention will now be described in detail.

[0029] On one hand, the present invention provides allantoin microneedle-like crystals with an average length of 5 to 500 μm for their long axis.

[0030] Allantoin (C4H6N4O3, molecular weight 158.116 g / mol, IUPAC name: (2,5-dioxo-4-imidazolidinyl)urea), CAS No. 97-59-6, EC No. 202-592-8) according to one aspect of the present invention is a general pharmaceutical product approved by the US FDA as an effective ingredient for skin protection, and is known to be a poorly soluble component. The allantoin can be represented by the following chemical formula 1:

[0031] [Chemical Formula 1]

[0032]

[0033] In one embodiment of the present invention, allantoin crystals have a microneedle-like structure, which can cause slight irritation to the skin when applied, thereby promoting absorption within the skin.

[0034] According to an embodiment of the present invention, the average length of the long axis of the allantoin microneedle crystals can be from 5 to 500 μm. Specifically, the average length of the long axis of the allantoin microneedle crystals can be 5 μm or more, 10 μm or more, 20 μm or more, 30 μm or more, 40 μm or more, 50 μm or more, 55 μm or more, 60 μm or more, 65 μm or more, 70 μm or more, 75 μm or more, 80 μm or more, 85 μm or more, 90 μm or more, 92 μm or more, 94 μm or more, 95 μm or more, 96 μm or more, 98 μm or more, 100 μm or more, 110 μm or more, 120 μm or more, 130 μm or more, 140 μm or more, 150 μm or more, 160 μm or more, 170 μm or more, 180 μm or more, 190 μm or more, 200 μm or more, 250 μm or more, or 300 μm. Above, 350μm and above, 400μm and above or above 450μm, can be below 500μm, below 450μm, below 400μm, below 350μm, below 300μm, below 250μm, below 240μm, below 230μm, below 225μm, below 220μm, below 218μm, below 216μm, below 214μm, below 212μm, below 210μm, below 208μm, below 206μm, below 204μm, below 202μm, below 200μm, below 180μm, below 160μm, below 140μm, below 120μm, below 100μm, below 90μm, below 80μm, below 70μm or below 60μm. More specifically, the average length of the long axis of the allantoin microneedle crystals can be 100 to 200 μm, and even more specifically, it can be 150 to 200 μm.

[0035] According to one aspect of the present invention, the thickness of the allantoin microneedle crystals can be greater than 0 μm and less than or equal to 40 μm. Specifically, the thickness of the allantoin microneedle crystals can be greater than 0 μm, greater than 2 μm, greater than 4 μm, greater than 5 μm, greater than 6 μm, greater than 7 μm, greater than 8 μm, greater than 9 μm, greater than 10 μm, greater than 11 μm, greater than 12 μm, greater than 13 μm, greater than 14 μm, greater than 15 μm, greater than 16 μm, greater than 17 μm, greater than 18 μm, greater than 19 μm, greater than 20 μm, greater than 22 μm, greater than 24 μm, greater than 26 μm. The thickness can be greater than 1 μm, greater than 28 μm, greater than 30 μm, or greater than 35 μm, and can be less than 40 μm, less than 38 μm, less than 36 μm, less than 34 μm, less than 32 μm, less than 30 μm, less than 29 μm, less than 28 μm, less than 27 μm, less than 26 μm, less than 25 μm, less than 24 μm, less than 23 μm, less than 22 μm, less than 21 μm, less than 20 μm, less than 15 μm, less than 10 μm, or less than 8 μm. More specifically, the thickness of the allantoin microneedle-like crystals can be 10 to 20 μm. According to one aspect of the invention, the allantoin microneedle-like crystals have a thickness greater than 0 μm and less than or equal to 40 μm, thereby enabling them to slightly penetrate the skin surface and pass through the stratum corneum.

[0036] According to one aspect of the present invention, allantoin microneedle-like crystals can be crystallized by precipitating amorphous allantoin using an antisolvent crystallization method.

[0037] According to one aspect of the present invention, the allantoin microneedle crystals can be soluble. The allantoin microneedle crystals can be water-soluble or lipid-soluble. According to one embodiment of the present invention, the allantoin microneedle crystals according to one aspect of the present invention have excellent solubility in solvents, thus possessing soluble properties and solving the problem of poor solubility inherent in general allantoin powders (see preparation examples and Tables 1 and 2).

[0038] According to one aspect of the present invention, allantoin microneedle-shaped crystals can penetrate into the skin when applied to the skin. Furthermore, according to one aspect of the present invention, allantoin microneedle-shaped crystals can remain within the stratum corneum of the skin 2 to 36 hours after application. Specifically, the allantoin microneedle-shaped crystals can remain within the stratum corneum of the skin after 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 24 hours, 30 hours, or 36 hours after application. According to one embodiment of the present invention, by having a microneedle-like morphology similar to a needle, it remains within the stratum corneum even after a long period of time after application, thus allowing it to penetrate into the skin and be absorbed simply by applying it to the skin (see Experimental Example 1 and...). Figure 4b ).

[0039] According to one aspect of the invention, allantoin microneedle crystals can dissolve and be absorbed into the skin after application. The process is as follows: First, when allantoin microneedle crystals are applied to the skin, the crystals themselves adhere to the skin surface directly. Then, the applied allantoin microneedle crystals have a thickness greater than 0 μm and less than or equal to 40 μm, specifically 5 to 40 μm, allowing for slight penetration into the skin surface and through the stratum corneum. At this point, the allantoin component can be immediately delivered into the skin, and absorption is further promoted due to the slight stimulation of the skin by the microneedle structure. Subsequently, rolling or rubbing the skin surface with the hand or fingers approximately 10 times maximizes the contact between the allantoin microneedles and the skin surface, thereby facilitating successful penetration. The rolling or rubbing action promotes the dissolution and absorption of the allantoin microneedle crystals in the skin, and the microstimulation is also expected to improve microcirculation. Furthermore, allantoin microneedle-like crystals that penetrate the skin or stratum corneum gradually dissolve upon contact with moisture within the skin, releasing allantoin. This process can occur within 2 to 36 hours after application. Specifically, absorption occurs initially within the stratum corneum (keratin layer), where it reacts with subcutaneous moisture and gradually dissolves. Some components then reach the epidermis and are reabsorbed. Typically, most of the allantoin microneedle-like crystals dissolve and are absorbed within the stratum corneum.

[0040] According to one aspect of the invention, allantoin microneedle crystals can be dissolved and absorbed in the skin after being repeatedly rolled 10 times at a weight of 0.5 to 1.0 kg / cm². The allantoin microneedle crystals can be dissolved and absorbed in the skin after 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 12 hours, 15 hours, 18 hours, 21 hours, 24 hours, 27 hours, 30 hours, 33 hours, or 36 hours after application, but can be further dissolved and absorbed by rolling with the hands or fingers. Specifically, allantoin microneedle crystals can be dissolved in the skin and absorbed by the stratum corneum after being applied to the skin and repeatedly rolled 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times at weights of 0.5 kg / cm² or more, 0.6 kg / cm² or more, 0.7 kg / cm² or more, 0.8 kg / cm² or less, 0.7 kg / cm² or less, 0.7 kg / cm² or less. The rolling or rubbing motion can promote the dissolution of allantoin microneedle crystals and their absorption by the skin, and the microstimulation is also expected to improve microcirculation.

[0041] According to one aspect of the present invention, the allantoin microneedle crystals may contain 3 to 16% by weight of allantoin, based on the total weight of the allantoin microneedle crystals. Specifically, the allantoin microneedle crystals may contain 3% or more, 3.5% or more, 4% or more, 4.2% or more, 4.4% or more, 4.6% or more, 4.8% or more, 5% or more, 5.2% or more, 5.4% or more, 5.6% or more, 5.8% or more, 6% or more, 7% or more, 8% or more, 9% or more, 10% or more, or 11% or more by weight of allantoin, based on the total weight of the allantoin microneedle crystals. The allantoin may be present in concentrations of 12% or more, or 14% or more, but may also contain less than 16% by weight, less than 15% by weight, less than 14% by weight, less than 13% by weight, less than 12% by weight, less than 11% by weight, less than 10% by weight, less than 9% by weight, less than 8.8% by weight, less than 8.6% by weight, less than 8.4% by weight, less than 8.2% by weight, less than 8% by weight, less than 7.8% by weight, less than 7.6% by weight, less than 7.4% by weight, less than 7.2% by weight, less than 7% by weight, less than 6% by weight, less than 5% by weight, or less than 4% by weight. More specifically, the allantoin microneedle crystals may contain 4 to 9% by weight of allantoin, based on the total weight of the allantoin microneedle crystals.

[0042] According to one aspect of the invention, the allantoin microneedle crystals may further contain betaine. When the allantoin microneedle crystals contain betaine, allantoin can be crystallized into a microneedle form with higher purity and yield.

[0043] According to one aspect of the present invention, the allantoin microneedle crystals, based on the total weight of the allantoin microneedle crystals, may contain 9 to 72% by weight of betaine. Specifically, the allantoin microneedle crystals, based on the total weight of the allantoin microneedle crystals, may contain 9% or more, 10% or more, 12% or more, 14% or more, 16% or more, 18% or more, 20% or more, 22% or more, 24% or more, 26% or more, 28% or more, 30% or more, 35% or more, 36% or more, 40% or more, 50% or more, or 60% by weight of betaine. The above-mentioned amounts may contain less than 72% by weight, less than 70% by weight, less than 60% by weight, less than 50% by weight, less than 40% by weight, less than 38% by weight, less than 36% by weight, less than 34% by weight, less than 32% by weight, less than 30% by weight, less than 28% by weight, less than 26% by weight, less than 24% by weight, less than 22% by weight, less than 20% by weight, less than 19% by weight, less than 18% by weight, less than 16% by weight, less than 14% by weight, less than 12% by weight, or less than 10% by weight. More specifically, the allantoin microneedle crystals may contain 12 to 36% by weight of betaine based on the total weight of the allantoin microneedle crystals.

[0044] On the other hand, the present invention provides a cosmetic composition comprising allantoin microneedle crystals as an active ingredient. The description of the allantoin microneedle crystals also applies to the cosmetic composition.

[0045] According to one aspect of the present invention, the cosmetic composition may contain 3 to 12 by weight of the allantoin microneedle crystals based on the total weight of the composition. Specifically, the cosmetic composition, based on the total weight of the composition, may contain more than 3% by weight, more than 3.5% by weight, more than 4% by weight, more than 4.2% by weight, more than 4.4% by weight, more than 4.6% by weight, more than 4.8% by weight, more than 5% by weight, more than 5.2% by weight, more than 5.4% by weight, more than 5.6% by weight, more than 5.8% by weight, more than 6% by weight, more than 7% by weight, more than 8% by weight, more than 9% by weight, or more than 10% by weight, or may contain less than 12% by weight, less than 11% by weight, less than 10% by weight, less than 9% by weight, less than 8.8% by weight, less than 8.6% by weight, less than 8.4% by weight, less than 8.2% by weight, less than 8% by weight, less than 7.8% by weight, less than 7.6% by weight, less than 7.4% by weight, less than 7.2% by weight, less than 7% by weight, less than 6% by weight, less than 5% by weight, or less than 4% by weight. More specifically, the cosmetic composition may contain 4 to 9 by weight of the allantoin microneedle crystals, based on the total weight of the composition.

[0046] The cosmetic composition according to one aspect of the invention may further contain betaine. When the allantoin microneedle crystals contain betaine, allantoin can be crystallized into a microneedle form with higher purity and yield.

[0047] The cosmetic composition according to one aspect of the invention can be used for exfoliation, for skin moisturizing, for skin wound healing, for promoting skin regeneration, or for protecting the skin from irritation.

[0048] The compositions according to one aspect of the invention can be in the form of cosmetic compositions containing a media or matrix acceptable to cosmetics or dermatology. They are available in all dosage forms suitable for topical application, for example, as solutions, gels, solids, anhydrous pastes, emulsions obtained by dispersing an oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, microspheres, or ionic (liposomes) and nonionic cysteine ​​dispersions, or as creams, lotions, emulsions, powders, ointments, sprays, or concealer sticks. These compositions can be prepared according to conventional methods in the art. Furthermore, the compositions according to this disclosure can also be used in the form of foams or, further, as aerosol compositions containing compressed propellants.

[0049] According to one aspect of the present invention, the dosage form of the cosmetic composition is not particularly limited, and for example, it can be formulated as a gentle lotion, astringent lotion, nourishing lotion, nourishing cream, massage cream, serum, eye cream, eye essence, cleansing cream, cleansing foam, makeup remover, cleansing wipes containing the cosmetic composition, face mask, powder, body lotion, moisturizing cream, moisturizing oil and moisturizing essence, etc.

[0050] When the dosage form of the cosmetic composition is a paste, cream, or gel, the composition according to one aspect of the present invention may utilize animal oils, vegetable oils, waxes, paraffin wax, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide as carrier components.

[0051] When the cosmetic composition is in the form of a powder or a spray, the composition according to one aspect of the invention may utilize lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder as a carrier component, especially in the case of a spray, and may further include a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether.

[0052] When the dosage form of the cosmetic composition is a solution or emulsion, the composition according to one aspect of the present invention utilizes a solvent, solvator or emulsifier as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylethylene glycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid esters of sorbitol.

[0053] When the dosage form of the cosmetic composition is a suspension, the composition according to one aspect of the present invention may utilize liquid diluents such as water, ethanol or propylene glycol; suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitan ester and polyoxyethylene sorbitan anhydride ester; microcrystalline cellulose; aluminum hydroxide; bentonite, agar or astragalus gum, etc., as carrier components.

[0054] The composition according to one aspect of the invention may further comprise functional additives and ingredients commonly found in conventional cosmetic compositions. As said functional additives, they may include ingredients selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, squalane, sphingolipids, and seaweed concentrate.

[0055] Furthermore, in addition to the aforementioned functional additives, the compositions according to one aspect of the present invention may, if necessary, include ingredients typically found in cosmetic compositions. Examples of such additional formulation ingredients include oils, moisturizers, lubricants, emulsifiers, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, etc.

[0056] On the other hand, the present invention may relate to a method for exfoliation, skin moisturization, skin wound healing, promoting skin regeneration, or protecting the skin from irritation, the method comprising the step of applying or administering allantoin microneedle crystals to an individual who requires exfoliation, skin moisturization, skin wound healing, promoting skin regeneration, or protecting the skin from irritation.

[0057] In another aspect, the present invention may relate to the use of allantoin microneedle crystals in the preparation of pharmaceutical compositions for exfoliation, skin moisturizing, skin wound healing, promoting skin regeneration, or protecting the skin from irritation.

[0058] In another aspect, the present invention may relate to the use of allantoin microneedle crystals in the preparation of cosmetic compositions for exfoliation, skin moisturizing, skin wound healing, promoting skin regeneration, or protecting the skin from irritation.

[0059] In another aspect, the present invention may relate to the use of allantoin microneedle crystals in the preparation of food compositions for exfoliation, skin moisturizing, skin wound healing, promoting skin regeneration, or protecting the skin from irritation.

[0060] In another aspect, the present invention may relate to the use of allantoin microneedle crystals for exfoliation, skin moisturizing, skin wound healing, promoting skin regeneration, or protecting the skin from irritation.

[0061] The present disclosure is further described by the following implementation examples, which do not limit the scope of the claims.

[0062] Example 1. A needle-like crystal of allantoin with an average length of 5 to 500 μm along its long axis.

[0063] Implementation Example 2. An allantoin microneedle crystal, according to Implementation Example 1, wherein the thickness of the allantoin microneedle crystal is greater than 0 μm and less than or equal to 40 μm.

[0064] Implementation Example 3. An allantoin microneedle-shaped crystal, according to Implementation Example 1 or 2, wherein the allantoin microneedle-shaped crystal is soluble.

[0065] Implementation Example 4. An allantoin microneedle crystal, according to any one of Implementation Examples 1 to 3, wherein the allantoin microneedle crystal penetrates into the skin when applied to the skin.

[0066] Example 5. An allantoin microneedle crystal, according to any one of Examples 1 to 4, wherein the allantoin microneedle crystal exists within the stratum corneum of the skin after being applied to the skin for 2 to 36 hours.

[0067] Example 6. An allantoin microneedle crystal, according to any one of Examples 1 to 5, wherein the allantoin microneedle crystal, after being applied to the skin, is dissolved and absorbed in the skin when repeatedly rolled 10 times at a weight of 0.5 to 1.0 kg / cm².

[0068] Implementation Example 7. An allantoin microneedle crystal, according to any one of Implementation Examples 1 to 6, wherein the allantoin microneedle crystal further comprises betaine.

[0069] Example 8. A cosmetic composition comprising allantoin microneedle crystals as described in any one of Examples 1 to 7 as an active ingredient.

[0070] Implementation Example 9. A cosmetic composition according to Implementation Example 8, wherein the cosmetic composition is used for exfoliation, for skin moisturizing, for skin wound healing, for promoting skin regeneration, or for protecting the skin from irritation.

[0071] The following preparation examples, embodiments, and experimental examples will be used to describe the structure and effects of the present invention in more detail. However, the following preparation examples, embodiments, and experimental examples are for illustrative purposes only to help understand the present invention and are not intended to limit the scope and range of the present invention.

[0072] [Preparation Example] Preparation of allantoin microneedle crystals

[0073] Allantoin powder (C4H6N4O3, molecular weight 158.116 g / mol, IUPAC name: (2,5-dioxo-4-imidazolidinyl)urea, CAS No. 97-59-6, EC No. 202-592-8) (3% by weight based on the total weight of allantoin, polyol, and water) was completely dissolved in a polyol (e.g., glycerol), and water was added before precipitation to prepare the allantoin microneedle crystals of Example 1. Figure 1 Ordinary allantoin has an amorphous form, whereas, for example, Figure 1 As shown, the allantoin microneedle crystals of Example 1 have a needle-like morphology with an average length of 150 to 200 μm for the long axis.

[0074] Furthermore, using the same method as in Example 1, 6% by weight of powdered allantoin, based on the total weight of the composition, was dissolved in glycerin along with the ingredients listed in Tables 1 and 2 below. Water was then added, followed by precipitation, to prepare Examples 2 to 17. Subsequently, the solubility in glycerin, crystal morphology, and the sensation upon application to the skin were evaluated and are shown in Tables 1 and 2 below. Here, solubility is indicated by X for insoluble, △ for slightly soluble, and ○ for readily soluble. The sensation is an assessment of whether the feeling when applying Examples 2 to 17 to the face is similar to the feeling of receiving dermatological treatment.

[0075] Table 1

[0076] Unit: weight %

[0077]

[0078] Table 2

[0079] Unit: weight %

[0080]

[0081] As shown in Tables 1 and 2 above, Examples 2 to 7 were confirmed to have a purity of over 99% and a yield of over 96%, with amorphous allantoin crystals forming needle-like morphology. The allantoin microneedle crystals have a needle-like morphology with an average long axis length of 150 to 200 μm and a thickness of 5 to 40 μm. Figure 2 This is a photograph showing the dissolution of standard allantoin powder (Clariant Produkte (Deutschland) GmbH, ALLANTOIN Premium) in deionized water. Standard allantoin is in an amorphous form, whereas... Figure 3 A photograph showing the dissolution of the allantoin microneedle crystals from Example 5 in deionized water, indicating that the crystals crystallized into a needle-like morphology. In particular, due to the poor solubility of allantoin, its use as a cosmetic ingredient presents difficulties. As described in Tables 1 and 2... Figure 3 As shown, Examples 4 to 7 also exhibit excellent solubility in deionized water, thus overcoming this problem.

[0082] [Experimental Example 1] Confirmation of the skin penetration effect of allantoin microneedle crystals

[0083] To confirm whether the allantoin microneedle crystals prepared in the preparation example could penetrate into the skin, an in vitro (ex vivo) stratum corneum residue assessment experiment was conducted.

[0084] Allantoin microneedle crystals stained with Nile-red (Sigma Aldrich, 72485-100mg) were applied to the epidermis of an in vitro skin biopsy tissue (Genoskin, NativeSkin™ #NSA20) taken from the abdomen of a 54-year-old woman, with a diameter of 20 mm. A cross-sectional image of the skin biopsy tissue was then taken after 18 hours. The image is shown below. Figure 4b As shown. As a control group, allantoin powder (ClariantProdukte (Deutschland) GmbH, ALANTOIN Premium) was applied to skin biopsy tissue using the same method, and its cross-section was photographed; the image is shown below. Figure 4a As shown. The specific experimental procedure is as follows.

[0085] Fluorescent staining

[0086] The fluorescent staining is performed by dissolving the Nile Red fluorescent dye reagent in DMSO solution to a concentration of 1 mg / mL. To stain the allantoin microneedle crystals or allantoin powder separately, Nile Red and raw material powder are mixed at a volume ratio of 5:1000 and stained at room temperature for 1 hour. Then, the allantoin microneedle crystals or allantoin powder are dissolved in deionized water (DI water) to a final concentration of 0.2% or 5%, thus preparing the sample.

[0087] Sample processing

[0088] On the day the skin biopsy tissue arrived, 2 mL of tissue culture medium was added, and the tissue was stabilized and cultured for 1 day in a 37°C, 5% CO2 incubator. The next day, 20 μL of allantoin microneedle crystal solution stained with Nile Red was dropped onto the epidermis and then rubbed with silicone rubber. After air-drying at 37°C for 1 hour using a thermomixer in a laminar flow hood, the tissue was further cultured for 17 hours in a 37°C, 5% CO2 incubator. 18 hours after application, the epidermis was rinsed with deionized water and fixed with formalin solution. Frozen sections of the fixed skin tissue were prepared and observed using a confocal laser scanning microscopy (Carl Zeiss, model: LSM980).

[0089] Microscope measurement conditions

[0090] To observe cross-sections of skin tissue, a 40X objective lens was used with an excitation wavelength of 561 nm and an emission wavelength of 600 to 700 nm. Three images of Nile red fluorescence and brightfield signals were acquired for each group.

[0091] like Figure 4b As shown, the allantoin powder in the control group remained on the outermost layer of the stratum corneum and could not penetrate the skin even after being applied for a long time. In contrast, the allantoin microneedle-like crystals in Example 5 remained inside the stratum corneum. Figure 4c This confirms that allantoin crystals, due to their needle-like shape, can easily penetrate into the skin and thus be absorbed by it.

[0092] Therefore, it can be understood that the allantoin crystals according to one aspect of the present invention, having the same microneedle-like morphology as needles, can penetrate into the skin and be absorbed by the skin simply by applying them to the skin.

[0093] [Experimental Example 2] Confirmation of the level of somatosensory perception of allantoin microneedle crystals

[0094] According to one aspect of the invention, allantoin microneedle crystals utilize microneedling technology, primarily used in dermatological cosmetic medical devices, to easily achieve similar effects at home as those using dermatological medical devices. Therefore, when the allantoin microneedle crystals are applied to the skin, it is important that they exhibit the same physical effects and benefits as dermatological treatments without being invasive. To this end, the perceived somatosensory effects were measured at different allantoin microneedle crystal concentrations.

[0095] First, cosmetic compositions containing allantoin microneedle crystals from Example 5 (Comparative Examples 1 and Examples 18 to 21) were prepared according to the ingredients and contents listed in Table 3 below, and a somatosensory perception experiment was conducted on five subjects in their 30s. The cosmetic compositions were prepared by mixing commonly used ingredients (specifically, purified water, butylene glycol, dipropylene glycol, glycerin, propylene glycol, 1,2-hexanediol, caprylic / capric triglyceride, ammonium acryloyl dimethyl taurate / VP copolymer, polyglycerol-6 caprylate, polyglycerol-4 caprate, hydrogenated lecithin, cholesterol, sodium methylstearoyl taurate, ethylhexylglycerin, and tocopherol) using methods commonly used in the cosmetics industry. The subjects applied Comparative Example 1 and Examples 18 to 21 to their forearms and performed finger rotation movements 10 times with a pressure of approximately 0.5 to 1.0 kg / cm². They then recorded their sensations according to a 5-point rating system as shown in Table 4 (no physical effect: 1 point, slight sensation: 2 points, moderate sensation: 3 points, strong sensation: 4 points, very strong sensation: 5 points). After all subjects completed the assessment, the scores recorded by each subject were collected, and the degree of sensation was analyzed based on the assessment scores to confirm the perceived sensation at each concentration. The results are shown in Table 5 below.

[0096] Table 3

[0097] Unit: weight %

[0098]

[0099] Table 4

[0100]

[0101] Table 5

[0102]

[0103] As shown in Table 5, with the increase of allantoin microneedle crystal content, the somatosensory perception of most subjects also increased. Figure 5This demonstrates the level of sensory perception based on the allantoin microneedle crystal content. Specifically, at concentrations above 3% by weight, most subjects experienced a slight tingling sensation on the skin. While a slight tingling and tactile sensation were perceived, post-use skin redness was not significant (average approximately 2). Furthermore, regarding residual sensation after use, most subjects experienced the microneedle crystals dissolving and disappearing after 10 rolls, resulting in almost no residual sensation. Therefore, it is evident that the allantoin microneedle crystals and compositions comprising them according to one aspect of the invention have the same morphology as microneedles, providing the same sensory effect as dermatological treatment, but without causing the stinging sensation of skin redness or pain, and without residual sensation due to the dissolution of the allantoin microneedle crystals, making them suitable even for sensitive skin.

[0104] [Experimental Example 3] Safety Confirmation of Allantoin Microneedle Crystals

[0105] As can be seen from Experiment 2, when allantoin microneedle crystals according to one aspect of the present invention are applied to the skin, they provide a stinging sensation to the skin. Therefore, in order to confirm its safety, the following safety confirmation experiment was conducted.

[0106] Using the same method as in Example 2, compositions were prepared including the allantoin microneedle crystals of Example 5 (diluted to a concentration of 5 (w / w%) with distilled water) and an essence formulation containing the allantoin microneedle crystals of Example 5 (the content of allantoin microneedle crystals was 5% by weight based on the total weight of the composition) (Example 22). Subsequently, 24-hour and 48-hour occlusive patch tests were performed on the upper back of 30 adult women (mean age 45.1 years) to assess stimulation scores, and the average values ​​are shown in Table 6 below.

[0107] Table 6

[0108] Unit: points

[0109]

[0110] As shown in Table 6, the allantoin microneedle crystals of Example 5 had a stimulation score of 1.25, indicating no irritation, while the composition containing allantoin microneedle crystals of Example 22 had a stimulation score of 0.0, indicating no irritation.

[0111] Therefore, it can be understood that the allantoin microneedle crystals and compositions containing them according to one aspect of the present invention provide the same sensory effects as dermatological treatments, but without skin irritation, and are therefore safe to use on sensitive skin.

[0112] [Experimental Example 4] Confirmation of the stability of allantoin microneedle crystals

[0113] The dosage form stability of the allantoin microneedle crystals prepared in the preparation examples was confirmed under various conditions, including room temperature, freezing, refrigeration, 37°C, 45°C, and cycling. Cycling conditions were performed at -10°C to 45°C for 12 hours each time to confirm dosage form stability. The samples used here were the allantoin microneedle crystals from Example 5. Each sample was taken over a period of four weeks within each of the six temperature ranges. After equilibration at room temperature for four hours, the properties of the contents were visually assessed, and then the changes in the properties of the allantoin microneedle crystals and whether they had dissolved were confirmed by electron microscopy. The results are as follows: Figure 6 As shown.

[0114] like Figure 6 As shown, even after being stored for four weeks under harsh conditions, the allantoin microneedle crystals according to one aspect of the present invention remain stable without any change in properties.

[0115] Therefore, it is understood that the allantoin microneedle crystals according to one aspect of the present invention are crystallized allantoin with excellent solubility, and can be used as a component of cosmetic compositions. The microneedle crystals have a needle-like morphology with an average length of 5 to 500 μm, specifically 150 to 200 μm, similar to that of needles. This allows them to penetrate into the skin and be absorbed simply by applying them to the skin. Moreover, they dissolve into the skin by rolling after application, exhibiting excellent safety. They remain stable and unchanged in properties even under harsh conditions, making them easy to store and distribute. They have excellent effects as an active ingredient delivery system for delivering various ingredients, specifically lipid-soluble or water-soluble active ingredients, into the skin.

[0116] Examples of dosage forms of compositions according to the present invention will be described below, but these are not intended to limit the invention, but only to illustrate the invention in detail.

[0117] [Dosage Form Example 1] Nourishing Toner

[0118] Nourishing toners can be prepared using conventional methods according to the components listed in Table 7 below.

[0119] Table 7

[0120]

[0121] [Dosage Form Example 2] Nutritional Emulsion

[0122] Nutritional emulsions can be prepared using conventional methods according to the components listed in Table 8 below.

[0123] Table 8

[0124]

[0125] [Dosage Form Example 3] Nourishing Cream

[0126] The nourishing cream can be prepared using conventional methods according to the components listed in Table 9 below.

[0127] Table 9

[0128]

[0129] [Dosage Form Example 4] Ointment

[0130] The ointment can be prepared using conventional methods according to the components listed in Table 10 below.

[0131] Table 10

[0132]

[0133] While specific aspects of the invention have been described above in detail, those skilled in the art should understand that these specific descriptions are merely preferred embodiments and are not intended to limit the scope of the invention. Therefore, the essential scope of the invention will be defined by the appended claims and their equivalents.

Claims

1. Allantoin microneedle-like crystals having an average length of 5 to 500 μm along their long axis.

2. The allantoin microneedle crystals according to claim 1, wherein, The thickness of the allantoin microneedle crystals is greater than 0 μm and less than or equal to 40 μm.

3. The allantoin microneedle crystals according to claim 1, wherein, The allantoin microneedle-shaped crystals are soluble.

4. The allantoin microneedle crystals according to claim 1, wherein, The allantoin microneedle-shaped crystals penetrate the skin when applied.

5. The allantoin microneedle crystals according to claim 1, wherein, The allantoin microneedle-like crystals remain within the stratum corneum of the skin for 2 to 36 hours after application.

6. The allantoin microneedle crystals according to claim 1, wherein, The allantoin microneedle crystals, after being applied to the skin, dissolve and are absorbed when rolled repeatedly 10 times at a weight of 0.5 to 1.0 kg / cm².

7. The allantoin microneedle crystals according to claim 1, wherein, The allantoin microneedle-like crystals also contain betaine.

8. A cosmetic composition comprising allantoin microneedle crystals as an active ingredient, as described in any one of claims 1 to 7.

9. Use of allantoin microneedle crystals according to any one of claims 1 to 7 in the preparation of cosmetic compositions for exfoliation, skin moisturizing, skin wound healing, promoting skin regeneration, or protecting the skin from irritation.

10. Use of allantoin microneedle crystals according to any one of claims 1 to 7 in the preparation of a pharmaceutical composition for skin wound healing.

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