Microneedle patch composition for acne treatment, method for manufacturing microneedle patch, and microneedle patch for acne treatment

Abstract

The present invention relates to a microneedle patch composition for acne treatment, a method for manufacturing a microneedle patch, and a microneedle patch for acne treatment, and more specifically, to a microneedle patch that is effective for acne treatment, and a manufacturing method therefor.

Description

Microneedle patch composition for acne treatment, method for manufacturing microneedle patch, and microneedle patch for acne treatment

[0001] The present invention relates to a microneedle patch composition for acne treatment, a method for manufacturing a microneedle patch, and a microneedle patch for acne treatment, and more particularly, to a microneedle patch effective for acne treatment and a method for manufacturing the same.

[0002] Acne occurs due to a complex interaction of various factors. The most important cause is the enlargement and activation of sebaceous glands during puberty, which leads to excessive sebum secretion, resulting in abnormalities in the keratinocyte process, resulting in dyskeratosis or hyperkeratosis of keratinocytes. As a result, sebum is unable to be secreted naturally and accumulates in the hair follicle along with keratin and cell debris, resulting in the formation of comedones, the characteristic lesion of acne. Comedones are divided into blackhead comedones and whitehead comedones depending on their shape. When bacteria such as Propionibacterium acnes proliferate, they create inflammatory lesions, resulting in visible red or swollen acne lesions such as papules, pustules, and nodules.

[0003] Therefore, to be useful, a drug for acne must have at least one of the following functions: regulating sebum secretion, correcting abnormalities in the keratinization process, and suppressing bacteria such as Propionibacterium acnes.

[0004] Among acne treatment drugs, there is no topical application that has been clearly proven to have a sebum secretion suppressing effect, and comedolytic agents or antibacterial agents are commonly used.

[0005] These acne medications can be used in gel form, etc. That is, the user applies the gel containing the acne medication to the acne-affected skin.

[0006] However, these gel types are cumbersome to use, as they tend to get on the user's hands. Furthermore, since they are applied to the skin's surface, the medication may not effectively penetrate the skin. Furthermore, if applied to the skin, the medication may stain clothing and other surfaces during activity, potentially reducing its effectiveness.

[0007] The present invention aims to solve the above problems by providing a microneedle patch composition for acne treatment, a method for manufacturing the composition, and a microneedle patch for acne treatment, which are convenient to use and can effectively penetrate an acne treatment drug into the skin.

[0008] The above-described object of the present invention can be achieved by a microneedle patch composition for treating acne, characterized in that it comprises nicotinamide, salicylic acid, oligopeptide-10, phytosphingosine HCL, and a biodegradable polymer compound.

[0009] Here, the biodegradable polymer compound may be included in an amount of 60.0 wt% to 90.0 wt%, the nicotinic acid amide may be included in an amount of 3.0 wt% to 7.0 wt%, the salicylic acid may be included in an amount of 1.0 wt% to 2.0 wt%, the oligopeptide-10 may be included in an amount of 3.0 wt% to 7.0 wt%, and the phytosphingosine HCL may be included in an amount of 3.0 wt% to 7.0 wt%.

[0010] In addition, the biodegradable polymer compound is hyaluronic acid and its salts, polyvinylpyrrolidone, polyvinyl alcohol, cellulose polymer, dextran, gelatin, glycerin, polyethylene glycol, polysorbate, propylene glycol, povidone, carbomer, gum ghatti, guar gum, glucomannan, glucosamine, dammer resin, rennet casein, locust bean gum, microfibrillated cellulose, psyllium seed gum, xanthan gum, arabino galactan, gum arabic, alginic acid, gelatin, gellan gum, carrageenan, karaya gum, curdlan, chitosan, chitin, tara gum. gum), tamarind gum, tragacanth gum, furcelleran, pectin or pullulan, hydroxypropyl methylcellulose, hydroxyalkyl cellulose, ethyl hydroxyethyl cellulose, alkyl cellulose and carboxymethyl cellulose.

[0011] Meanwhile, the above object of the present invention can be achieved by a method for manufacturing a microneedle patch for acne treatment, characterized by comprising the steps of providing a pair of sheets, spotting the microneedle patch composition on at least one of the pair of sheets, moving the pair of sheets relatively close to each other so that the composition is brought into contact with each other between the pair of sheets, and solidifying the composition and spacing the pair of sheets apart to form microneedles on the pair of sheets.

[0012] In addition, the above-described object of the present invention can be achieved by a microneedle patch for acne treatment manufactured by the above-described manufacturing method, which includes nicotinamide, salicylic acid, oligopeptide-10, phytosphingosine HCL, and a biodegradable polymer compound.

[0013] According to the present invention having the above-described configuration, it is convenient to use and can effectively penetrate an acne treatment drug into the skin.

[0014] Figure 1 is a drawing illustrating a method for manufacturing a microneedle patch for acne treatment.

[0015] Figure 2 is a photograph showing the molding results of microneedles according to the change in the weight % of oligopeptide-10 and biodegradable polymer compound.

[0016] Figure 3 is a photograph of the area surrounding the hair follicles in the subcutaneous dermis of a rabbit.

[0017] Figure 4 (A) is a graph showing the IL-1β results, Figure 4 (B) is a graph showing the IL-6 results, and Figure 4 (C) is a graph showing the TNF-α results.

[0018] Hereinafter, a microneedle patch composition for acne treatment, a method for manufacturing the composition, and a microneedle patch for acne treatment according to an embodiment of the present invention will be described in detail.

[0019]

[0020] 1. Method for manufacturing a microneedle patch composition for acne treatment

[0021]

[0022] The microneedle patch composition for acne treatment according to the present invention may include nicotinamide, salicylic acid, oligopeptide-10, phytosphingosine HCl, and a biodegradable polymer compound.

[0023] Here, nicotinamide exhibits various effective actions in the treatment of acne. Specifically, it exhibits anti-inflammatory effects by suppressing the production of inflammatory cytokines and suppresses sebum secretion by regulating excessive sebaceous gland activity. It also exhibits antibacterial effects against Cutibacterium acnes and protects skin cells by reducing oxidative stress. Furthermore, it improves acne scars by alleviating post-inflammatory hyperpigmentation and strengthens the skin barrier function by promoting ceramide production. These complex actions make nicotinamide an effective ingredient suitable for sensitive and acne-prone skin.

[0024] Furthermore, salicylic acid, an organic acid with a β-hydroxy acid (BHA) structure, is widely used as an effective acne treatment. This ingredient promotes the removal of dead skin cells and sebum from pores through its keratolytic action, preventing the formation of acne caused by excessive sebum secretion. It also exhibits anti-inflammatory properties by suppressing the production of inflammatory mediators, and its ability to penetrate pores improves the acne-causing environment. Furthermore, it increases skin turnover, which can help alleviate post-acne pigmentation and improve skin tone.

[0025] Phytosphingosine hydrochloride (HPLC) is a bioactive substance with a structure similar to skin lipids, exhibiting anti-inflammatory and antibacterial activities that are effective in treating acne. This ingredient suppresses the initial cause of acne through its antibacterial action against Cutibacterium acnes and, by inhibiting the production of inflammatory mediators, contributes to the alleviation of inflammatory lesions. It also promotes skin barrier recovery, reducing irritation in sensitive acne-prone skin, and effectively prevents comedones by regulating sebum and keratin production.

[0026] First, since phytosphingosine HCL exists in a solid state at room temperature, 5.0 wt% to 20.0 wt% of the composition is dissolved by heating to approximately 60°C and stored at 60°C.

[0027] Next, nicotinamide, salicylic acid, oligopeptide-10, and phytosphingosine HCl are mixed with water, mixed in a planetary mixer at approximately 500 rpm for 1 minute, and then mixed again at 1400 rpm for 5 minutes. This process is repeated 1 to 2 times to prepare a primary mixture.

[0028] Afterwards, the biodegradable polymer compound is mixed into the primary mixture.

[0029] Here, the biodegradable polymer compound is hyaluronic acid and its salt, polyvinylpyrrolidone, polyvinyl alcohol, cellulose polymer, dextran, gelatin, glycerin, polyethylene glycol, polysorbate, propylene glycol, povidone, carbomer, gum ghatti, guar gum, glucomannan, glucosamine, dammer resin, rennet casein, locust bean gum, microfibrillated cellulose, psyllium seed gum, xanthan gum, arabino galactan, gum arabic, alginic acid, gelatin, gellan gum, carrageenan, karaya gum, curdlan, chitosan, chitin, tara gum. gum), tamarind gum, tragacanth gum, furcelleran, pectin or pullulan, hydroxypropyl methylcellulose, hydroxyalkyl cellulose, ethyl hydroxyethyl cellulose, alkyl cellulose and carboxymethyl cellulose.

[0030] In the present invention, hyaluronic acid is used as the biodegradable polymer compound.

[0031] For example, hyaluronic acid having a molecular weight of approximately 150 to 200 kDa is added to the primary mixture, mixed in a planetary mixer at approximately 500 rpm for 1 minute, and then mixed at 1400 rpm for 15 minutes, repeating this process 2 to 3 times to prepare a secondary mixture.

[0032] Next, hyaluronic acid having a molecular weight of approximately 50 to 100 kDa is added to the secondary mixture, mixed in a planetary mixer at approximately 500 rpm for 1 minute, and then mixed at 1400 rpm for 5 minutes. This process is repeated 8 to 12 times to prepare a patch composition.

[0033]

[0034] 2. Microneedle patch composition for acne treatment

[0035]

[0036] The microneedle patch composition for acne treatment manufactured by the above-described manufacturing method may include nicotinamide, salicylic acid, oligopeptide-10, phytosphingosine HCL, and a biodegradable polymer compound.

[0037] As described above, in the present embodiment, hyaluronic acid is used as the biodegradable polymer compound.

[0038] Here, the microneedle patch composition from which water has been removed may include 60.0 wt% to 90.0 wt% of the biodegradable polymer compound, 3.0 wt% to 7.0 wt% of the nicotinic acid amide, 1.0 wt% to 2.0 wt% of the salicylic acid, 3.0 wt% to 7.0 wt% of the oligopeptide-10, and 3.0 wt% to 7.0 wt% of the phytosphingosine HCL.

[0039] If the above nicotinic acid amide is less than 3.0 wt%, the acne treatment effect is significantly reduced, whereas if it exceeds 7.0 wt%, skin irritation may become severe.

[0040] In addition, if the salicylic acid is less than 1.0 wt%, the exfoliating effect on acne is minimal, whereas if it exceeds 2.0 wt%, the possibility of causing dry skin increases.

[0041] Furthermore, when used in combination with salicylic acid, the oligopeptide-10 can more than double the antibacterial activity. Furthermore, the weight ratio of the oligopeptide-10 is closely related to the manufacturing method of the microneedle patch, as described below. This will be further detailed later.

[0042]

[0043] 3. Microneedle patches for acne treatment

[0044]

[0045] Next, a microneedle patch is manufactured using the aforementioned microneedle patch composition.

[0046] Figure 1 is a drawing illustrating a method for manufacturing a microneedle patch for acne treatment.

[0047] Referring to FIG. 1, a method for manufacturing a microneedle patch according to the present embodiment may include the steps of first providing a pair of sheets (20, 20'), spotting the microneedle patch composition (13, 13') on at least one of the pair of sheets (20, 20'), moving the pair of sheets (20, 20') relatively so that they come close to each other to bring the composition (13, 13') between the pair of sheets (20, 20') into contact with each other, and solidifying the composition (13, 13') and spacing the pair of sheets (20, 20') apart to form microneedles (14, 14') on the pair of sheets (20, 20').

[0048] First, the pair of sheets (20, 20') may be provided with, for example, a pair of hydrophobic sheets (10, 10') and a water-soluble film (12, 12') formed on each of the pair of hydrophobic sheets (10, 10') and enhancing adhesiveness with the microneedles (14, 14').

[0049] The hydrophobic sheet (10, 10') may be provided, for example, on a pair of substrates (not shown). In this case, the hydrophobic sheet (10, 10') may be provided by being applied and dried on the substrates, or may be provided in a sheet state.

[0050] Meanwhile, water-soluble films (12, 12') are formed on top of each of the pair of hydrophobic sheets (10, 10'). The water-soluble films (12, 12') can be applied on the hydrophobic sheets (10, 10') to form a film layer.

[0051] The microneedle patch composition (13, 13') may be spotted on the above pair of sheets (20, 20'). In Fig. 1 (A), the viscous substance (13, 13') is depicted as being spotted on both the water-soluble films (12, 12') of the pair of sheets (20, 20'), but this is not limited thereto. For example, it is also possible to spot the viscous substance (13, 13') on only one of the water-soluble films (12, 12') of the pair of sheets (20, 20').

[0052] Next, the pair of sheets (20, 20') are moved relative to each other ((A) of FIG. 1) so that they come closer to each other, so that the viscous substance (13, 13') is brought into contact with each other between the water-soluble films (12, 12') of the pair of sheets (20, 20'), and the pair of sheets (20, 20') are spaced apart so that the viscous substance (13, 13') is tensioned ((B) of FIG. 1).

[0053] Meanwhile, when spotting a viscous substance (13, 13') on only one of the water-soluble films (12, 12') of a pair of sheets (20, 20'), if the pair of sheets (20, 20') move relative to each other so that they come closer to each other, the viscous substance (13, 13') and the water-soluble film (12, 12') on the opposite side can come into contact.

[0054] Next, the viscous material (13, 13') is solidified and the pair of sheets (20, 20') are separated to form microneedles (14, 4') on the water-soluble films (12, 12') of the pair of sheets (20, 20'), respectively.

[0055] In this case, the viscous material (13, 13') can be solidified by means of blowing air, etc. After the viscous material (13, 13') is sufficiently solidified, when the sheets (20, 20') are further separated, the viscous materials (13, 13') that were connected to each other are separated, and microneedles (14, 14') having tips are formed ((C) of FIG. 1), thereby manufacturing a microneedle patch (100, 100').

[0056] The microneedle patch for acne treatment manufactured through the aforementioned process may contain nicotinamide, salicylic acid, oligopeptide-10, phytosphingosine HCL, and a biodegradable polymer compound.

[0057] The method for manufacturing a microneedle patch according to Fig. 1 is called the so-called 'air-blowing method', and the applicant has secured a number of related patents.

[0058] For example, Korean Patent Registration No. 10-1136738 (Title of the invention: Method for producing solid microstructure by blowing and solid microstructure produced thereby), No. 10-125424 (Title of the invention: Method for producing microstructure), No. 10-1386440 (Title of the invention: Solid microstructure produced using blowing method and method for producing same), No. 10-1435888 (Title of the invention: Method for producing biodegradable microneedles using hyaluronic acid), No. 10-1636069 (Title of the invention: Method for producing microstructure), etc.

[0059] The inventor of the present invention changed the composition of the aforementioned microneedle patch composition and applied it to the blowing tension method and molding process according to FIG. 1.

[0060] CompositionBlend1Blend2Blend3Blend4Blend5Blend6Blend7Blend8Blend9Nicotinamide (wt%)5.05.05.05.05.05.05.05.05.05.05.0Salicylic acid (wt%)2.02.02.02.02.02.02.02.02.02.02.02.0Phytosphingosine HCL (wt%)5.05.05.05.05.05.05.05.05.05.0Polymer compound (wt%)88.087.086.085.084.083.082.081.080.0Oligopeptide-10 (wt%)0.01.02.03.04.05.06.07.08.0ResultImproper molding (mushroom cloud shape)Poor needle molding discharge

[0061] For example, an experiment was conducted by keeping the weight ratio of nicotinamide (5.0 wt%), salicylic acid (2.0 wt%), and phytosphingosine HCL (5.0 wt%) constant and changing the weight ratio of oligopeptide-10 and biodegradable polymer compound.

[0062] First, when applied to the molding process, it was confirmed that good microneedle patches were formed in all compositions from formulation 1 to formulation 9.

[0063] Next, the compositions of combinations 1 to 9 were applied to the blowing tension method. In this case, when oligopeptide-10 was included in amounts less than 3.0 wt% (combinations 1 to 3), it was confirmed that microneedles were not formed well, as shown in Fig. 2(A), in which the opposing needles were not separated but were attached to each other in a 'mushroom cloud' shape.

[0064] The reason for this was found to be that the viscosity of the composition changed as the weight % of oligopeptide-10 decreased, so that when the composition was tensioned in the blowing tension method ((B) of Fig. 1), sufficient viscosity required for tension was not secured.

[0065] On the other hand, when oligopeptide-10 was included in an amount of 3.0 wt% to 7.0 wt% (combination 4 to 8), it was confirmed that the viscosity of the composition was sufficiently secured, and a good microneedle patch was formed by the blowing tension method.

[0066] Figure 2(B) corresponds to a photograph of a microneedle manufactured by the blowing-injection method when oligopeptide-10 is included at 3.0 wt% to 7.0 wt%. The microneedle of Figure 2(B) has a solid structure, has homogeneous properties throughout the structure, and was measured to satisfy the length and strength conditions that enable good penetration into the body when attached to human skin.

[0067] Meanwhile, when the composition was discharged from a nozzle for spotting by blowing tension method ((A) of Fig. 1) when the composition contained oligopeptide-10 exceeding 7.0 wt% (Formulation 9), it was confirmed that the composition was not discharged. This was confirmed to be because the viscosity of the composition was too excessive, preventing smooth discharge from the nozzle.

[0068] As a result, it was confirmed that the viscosity of the composition is important in order to produce a microneedle patch according to the present invention by a blowing tension method, and in this case, it is necessary to include 3.0 wt% to 7.0 wt% of oligopeptide-10.

[0069]

[0070] 4. Experiments with microneedle patches for acne treatment

[0071]

[0072] The inventors of the present invention administered P. acnes to rabbits to induce acne, and then divided the rabbits into three groups: a group that did not receive any treatment (group 1, control), a group that applied a gel-type acne treatment agent according to the prior art once a day (group 2, Gel), and a group that attached and applied a microneedle patch for acne treatment according to the present invention once a day (group 3, Patch), and checked whether there were any changes in acne. The experiment was conducted for 12 days.

[0073] Furthermore, histological evaluation of acne-induced lesions collected after autopsy and Western blotting for inflammatory cytokines IL-1β, IL-6, and TNF-α were performed to evaluate the anti-acne effect of each group.

[0074] Figure 3 is a photograph of the area surrounding the hair follicles in the subcutaneous dermis of rabbits. Figure 3 (A) is a photograph of a group 1 rabbit, Figure 3 (B) is a photograph of a group 2 rabbit, and Figure 3 (C) is a photograph of a group 3 rabbit.

[0075] Looking at Figure 3, the results of the histological findings on acne lesions show that in the first group, moderate inflammatory cell infiltration was observed around the hair follicles in the subcutaneous dermis, while in the second group, the symptoms were alleviated compared to the first group, and in the third group, inflammatory cell infiltration was observed at a level corresponding to mild, with relatively more alleviation.

[0076] Figure 4 (A) is a graph showing the IL-1β results, Figure 4 (B) is a graph showing the IL-6 results, and Figure 4 (C) is a graph showing the TNF-α results.

[0077] Referring to (A) and (B) of Figure 4, a significant decrease was confirmed in both the second and third groups compared to the first group in the IL-1β and IL-6 results.

[0078] In addition, referring to (C) of Figure 4, in the TNF-α results, a significant decrease was confirmed in both the second and third groups compared to the first group, and in particular, a significant decrease was observed in the third group.

[0079] Finally, when the results of the IL-1β, IL-6, and TNF-α evaluations were combined, it was confirmed that the third group had the highest decreasing trend.

[0080] While the present invention has been described above with reference to preferred embodiments, those skilled in the art will appreciate that various modifications and variations can be made to the present invention without departing from the spirit and scope of the invention as defined in the claims below. Therefore, any modified implementation that fundamentally includes the elements of the claims should be considered within the technical scope of the present invention.

[0081] According to the present invention having the above-described configuration, it is convenient to use and can effectively penetrate an acne treatment drug into the skin.

Claims

1. A microneedle patch composition for acne treatment, characterized by comprising nicotinamide, salicylic acid, oligopeptide-10, phytosphingosine HCL, and a biodegradable polymer compound.

2. In paragraph 1, A microneedle patch composition for acne treatment, characterized in that the biodegradable polymer compound is contained in an amount of 60.0 to 90.0 wt%, the nicotinic acid amide is contained in an amount of 3.0 to 7.0 wt%, the salicylic acid is contained in an amount of 1.0 to 2.0 wt%, the oligopeptide-10 is contained in an amount of 3.0 to 7.0 wt%, and the phytosphingosine HCL is contained in an amount of 3.0 to 7.0 wt%.

3. In paragraph 1, The above biodegradable polymer compounds include hyaluronic acid and its salts, polyvinylpyrrolidone, polyvinyl alcohol, cellulose polymer, dextran, gelatin, glycerin, polyethylene glycol, polysorbate, propylene glycol, povidone, carbomer, gum ghatti, guar gum, glucomannan, glucosamine, dammer resin, rennet casein, locust bean gum, microfibrillated cellulose, psyllium seed gum, xanthan gum, arabino galactan, gum arabic, alginic acid, gelatin, gellan gum, carrageenan, karaya gum, curdlan, chitosan, chitin, tara gum, A microneedle patch composition for treating acne, characterized in that it comprises at least one selected from the group consisting of tamarind gum, tragacanth gum, furcelleran, pectin or pullulan, hydroxypropyl methylcellulose, hydroxyalkyl cellulose, ethyl hydroxyethyl cellulose, alkyl cellulose, and carboxymethyl cellulose.

4. The step of manufacturing a microneedle patch using the microneedle patch composition according to any one of paragraphs 1 and 3 Step of providing a pair of sheets; A step of spotting the microneedle patch composition onto at least one of the pair of sheets; A step of relatively moving the pair of sheets so that they come closer to each other and bringing the composition into contact with each other between the pair of sheets; and A method for manufacturing a microneedle patch for acne treatment, characterized by comprising the steps of: solidifying the composition and separating the pair of sheets to form microneedles on the pair of sheets.

5. A microneedle patch for acne treatment, manufactured using the manufacturing method according to Article 4, and containing nicotinamide, salicylic acid, oligopeptide-10, phytosphingosine HCL, and a biodegradable polymer compound.

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