Microneedles containing semaglutide and method for manufacturing the same

Abstract

This invention relates to a composition for manufacturing microneedles containing semaglutide and a biodegradable polymer material, microneedles, and a method for manufacturing microneedles. The microneedle manufacturing composition of this invention can produce microneedles that have a high semaglutide content and maintain strength suitable for skin penetration. Furthermore, microneedles of this invention or microneedles manufactured by the method of this invention can deliver a sufficient amount of drug into the body even in small quantities, and if the microneedle includes a drug-loading layer and a base structure layer, the amount of semaglutide remaining in the needle after application to the skin is small, thus reducing the loss of semaglutide.

Description

Technical Field

[0001] The present invention relates to microneedles containing semaglutide and a method for producing the same.

Background Art

[0002] Semaglutide is a glucagon-like peptide 1 receptor agonist, which is used as a therapeutic agent for type 2 diabetes and obesity and is classified as a long-term acting agonist.

[0003] Semaglutide is mainly used as an oral preparation or an injection. Semaglutide can be enzymatically decomposed in the digestive tract and intestinal mucosa, and can be poorly absorbed from the intestinal mucosa. In addition, there are many barriers such as first pass metabolism in the liver, so parenteral administration is more preferable than oral administration. On the other hand, in the case of an injection, it induces pain in the patients administered with it, there is a risk of secondary infection, and there is a problem that medical waste is generated. In addition, in the case of a self-injection preparation, since the patient has to inject himself / herself, the compliance with taking medicine is reduced due to a sense of fear and rejection, and thereby the therapeutic effect is also reduced.

[0004] Therefore, in fact, the development of a microneedle patch of semaglutide is required, and particularly, the development of a patch that can reduce the loss of semaglutide by having a small residual amount of semaglutide in the needle after application to the skin is required.

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object of the present invention is to provide a composition for producing microneedles having a high loading amount of semaglutide and maintaining a strength suitable for permeating the skin.

[0006] The present invention aims to provide a microneedle containing semaglutide that is easier to administer compared to self-injectable therapeutic drugs.

[0007] Furthermore, the present invention aims to provide a microneedle and a method for manufacturing the same that can reduce the amount of semaglutide remaining in the needle after application to the skin and reduce semaglutide loss. [Means for solving the problem]

[0008] [1] A composition for manufacturing microneedles, comprising semaglutide and a biodegradable polymer.

[0009] [2] The composition for manufacturing microneedles according to [1], wherein the biodegradable polymer substance is at least one selected from the group consisting of hyaluronic acid, polyvinylpyrrolidone, chondroitin, hydroxyethylcellulose, and hydroxypropylmethylcellulose.

[0010] [3] The composition for manufacturing microneedles according to [1], wherein the weight ratio of the semaglutide to the biodegradable polymer is 1:1.1 to 2.9.

[0011] [4] The microneedle manufacturing composition according to [1], comprising at least one selected from the group consisting of disodium hydrogen phosphate (Na2HPO4) and NaOH (sodium hydroxide).

[0012] [5] The microneedle manufacturing composition according to [1], further comprising at least one selected from the group consisting of trehalose and dextran.

[0013] [6] A microneedle comprising a drug-carrying layer comprising semaglutide and a biodegradable polymer.

[0014] [7] The microneedle according to [6], wherein the biodegradable polymer material of the drug-carrying layer is at least one selected from the group consisting of hyaluronic acid, polyvinylpyrrolidone, chondroitin, hydroxyethylcellulose, and hydroxypropylmethylcellulose.

[0015] [8] The microneedle according to [6], wherein the weight ratio of semaglutide to biodegradable polymer in the drug-carrying layer is 1:1.1 to 2.9.

[0016] [9] The microneedle according to [6], further comprising a base structural layer disposed on the bottom surface of the drug-carrying layer and comprising a biodegradable polymer substance.

[0017]

[10] The microneedle according to [9], wherein the base structural layer is formed from a viscous composition comprising a biodegradable polymer and water.

[0018]

[11] The microneedle according to

[10] , wherein the biodegradable polymer substance of the viscous composition is contained in an amount of 8 to 15% by weight relative to the total weight of the viscous composition.

[0019]

[12] The microneedle according to [9], wherein the biodegradable polymer material of the base structural layer is at least one selected from the group consisting of hyaluronic acid and carboxymethylcellulose.

[0020]

[13] A method for producing a microneedle, comprising the step of dropping a first viscous composition comprising semaglutide and a biodegradable polymer onto a first support to form a drug-carrying layer.

[0021]

[14] The method for producing a microneedle according to

[13] , wherein the step of forming the drug-carrying layer includes dropping the first viscous composition onto a plurality of spaced-apart locations on the first support, stretching the dropped first viscous composition, and drying the stretched first viscous composition.

[0022]

[15] The step of pulling the first viscous composition is performed by separating the first support and the second support after bringing the second support into contact with the dropped first viscous composition, and is the method for manufacturing the microneedle according to

[14] above.

[0023]

[16] The step of forming the drug-loaded layer further includes the step of cutting the dried first viscous composition, and is the method for manufacturing the microneedle according to

[14] above.

[0024]

[17] The biodegradable polymer substance of the first viscous composition is at least one selected from the group consisting of hyaluronic acid, polyvinylpyrrolidone, chondroitin, hydroxyethylcellulose, and hydroxypropylmethylcellulose, and is the method for manufacturing the microneedle according to

[13] above.

[0025]

[18] The weight ratio of semaglutide to the biodegradable polymer substance in the first viscous composition is 1:1.1 to 2.9, and is the method for manufacturing the microneedle according to

[13] above.

[0026]

[19] Before dropping the first viscous composition onto the first support, the method further includes the step of dropping a second viscous composition containing a biodegradable polymer substance onto the first support to form a base structure layer, The first viscous composition is dropped onto the base structure layer, and is the method for manufacturing the microneedle according to

[13] above.

[0027]

[20] The step of forming the base structure layer includes the step of dropping the second viscous composition onto a plurality of spaced-apart locations on the first support, and the step of drying the dropped second viscous composition, and is the method for manufacturing the microneedle according to

[19] above.

[0028]

[21] The second viscous composition contains a biodegradable polymer substance and water, and is the method for manufacturing the microneedle according to

[19] above.

[0029]

[22] The biodegradable polymer substance of the second viscous composition is contained at 8 to 15% by weight based on the total weight of the second viscous composition, and the method for manufacturing the microneedle according to

[21] .

[0030]

[23] The biodegradable polymer substance of the second viscous composition is at least one selected from the group consisting of hyaluronic acid and carboxymethyl cellulose, and the method for manufacturing the microneedle according to

[19] . [Advantages of the Invention]

[0031] The composition for manufacturing a microneedle of the present invention can manufacture a microneedle with a high loading amount of semaglutide and maintaining a strength suitable for permeating the skin.

[0032] Compared with the self-injection therapeutic agent containing semaglutide, the microneedle of the present invention can reduce the risks of bleeding, infection, pain, fear, etc., enhance the ease of taking the medicine by patients, and reduce medical waste.

[0033] In addition, while having sufficient strength to be inserted into the skin, the microneedle of the present invention includes a base structure layer at the lower end, so that after application to the skin, the residual amount of semaglutide in the drug loading layer on the base structure layer is small and the loss of semaglutide can be reduced. [Brief Description of the Drawings]

[0034] [Figure 1] FIG. 1 is a diagram showing the structure of a microneedle according to an exemplary embodiment. [Figure 2] FIG. 2 is a flowchart for explaining a method for manufacturing a microneedle according to an exemplary embodiment. [Figure 3] FIG. 3 is a flowchart for explaining a method for manufacturing a microneedle according to an exemplary embodiment. [Figure 4]Figure 4 is a diagram illustrating the maximum width and height of the base structural layer of a microneedle according to an exemplary embodiment. [Figure 5] Figure 5 shows the pharmacokinetic profiles of 1-layer, 1-layer, 2-layer, and 2-layer microneedles according to embodiments of the present invention. [Modes for carrying out the invention]

[0035] The present invention will be described in detail below.

[0036] This invention provides a composition for the manufacture of microneedles.

[0037] The microneedle manufacturing composition of the present invention comprises semaglutide and a biodegradable polymer material.

[0038] Semaglutide is a GLP-1 receptor agonist (glucagon-like peptide 1 receptor agonist) used to treat type 2 diabetes and obesity, and is classified as a long-term agonist.

[0039] The aforementioned biodegradable polymer substance refers to a polymer substance that can be broken down in a living organism by bodily fluids, enzymes, or microorganisms.

[0040] The biodegradable polymer substance can be at least one selected from the group consisting of hyaluronic acid (HA), polyvinylpyrrolidone (PVP), chondroitin, hydroxyethylcellulose (HEC), and hydroxypropyl methylcellulose (HPMC). In this case, compared to using different polymer substances, the composition for manufacturing microneedles can maintain a good state without curing or phase separation.

[0041] The average molecular weight of the hyaluronic acid can be 70 to 200 kDa. The average molecular weight of the chondroitin can be 20 to 80 kDa. The average molecular weight of the hydroxyethylcellulose (HEC) can be 300 to 720 kDa. The average molecular weight of the hydroxypropyl methylcellulose (HPMC) can be 10 to 80 kDa. In this case, it is possible to manufacture microneedles that maintain strength and shape suitable for skin penetration compared to cases outside the above range.

[0042] The weight ratio of the semaglutide to the biodegradable polymer may be 1:1.1 to 2.9, 1:1.2 to 2.8, 1:1.3 to 2.7, 1:1.4 to 2.6, 1:1.5 to 2.5, or 1:1.6 to 2.4.

[0043] The above-mentioned composition for manufacturing microneedles may further contain water as a solvent for dissolving semaglutide.

[0044] The microneedle manufacturing composition may further contain additives to increase the solubility of semaglutide. The additive may be, for example, at least one selected from the group consisting of disodium hydrogen phosphate (Na2HPO4) and NaOH (sodium hydroxide). The disodium hydrogen phosphate may be present in an amount of 0.5 to 2% by weight of the total weight of the microneedle manufacturing composition. The NaOH may be present in an amount of 0.1 to 0.25% by weight of the total weight of the microneedle manufacturing composition.

[0045] The microneedle manufacturing composition may further contain at least one selected from the group consisting of trehalose and dextran. The trehalose may be present in an amount of 0.1 to 5%, 1 to 4%, or 1.5 to 4.5% by weight of the total weight of the microneedle manufacturing composition. The dextran may be present in an amount of 0.1 to 6%, 0.5 to 5%, or 1 to 4.5% by weight of the total weight of the microneedle manufacturing composition.

[0046] The microneedle manufacturing composition of the present invention can produce microneedles that have a high semaglutide content and maintain strength suitable for skin penetration.

[0047] This invention provides microneedles.

[0048] The microneedle of the present invention includes a drug-carrying layer comprising semaglutide and a biodegradable polymer material.

[0049] The microneedles of the present invention may be soluble microneedles that release drugs as they degrade in the body.

[0050] The microneedle of the present invention can be a microneedle in which semaglutide is uniformly distributed throughout the entire structure. In this case, the microneedle may consist only of a drug-carrying layer.

[0051] The aforementioned semaglutide is as described above.

[0052] The biodegradable polymer material can be the same biodegradable polymer material used in the aforementioned microneedle manufacturing composition. For example, a material of the same type or having the same average molecular weight as the biodegradable polymer material contained in the aforementioned microneedle manufacturing composition can be used.

[0053] The weight ratio of the semaglutide to the biodegradable polymer may be 1:1.1 to 2.9, 1:1.2 to 2.8, 1:1.3 to 2.7, 1:1.4 to 2.6, 1:1.5 to 2.5, or 1:1.6 to 2.4.

[0054] The aforementioned drug-carrying layer may further contain at least one selected from the group consisting of the aforementioned additives disodium hydrogen phosphate (Na2HPO4) and NaOH (sodium hydroxide). Furthermore, the aforementioned drug-carrying layer may further contain at least one selected from the group consisting of the aforementioned additives trehalose and dextran.

[0055] The drug-carrying layer may be formed using the aforementioned microneedle manufacturing composition.

[0056] The microneedle of the present invention may further include a base structure layer disposed on the bottom surface of the drug-carrying layer and comprising a biodegradable polymer material. In this case, the microneedle of the present invention may have a lower end portion comprising the base structure layer and a drug-carrying layer formed on the base structure layer, as shown in Figure 1b.

[0057] The base structural layer does not necessarily have to contain a functional substance, such as semaglutide.

[0058] The base structural layer can be formed from a viscous composition (second viscous composition) containing a biodegradable polymer substance and water.

[0059] The biodegradable polymer substance in the viscous composition (second viscous composition) can be included in an amount of more than 5% but less than 20% by weight, 6 to 19% by weight, 7 to 18%, or 8 to 15% by mass relative to the total weight of the viscous composition. In this case, a base structure layer having a width and height that allows for the formation of a drug-carrying layer of an appropriate volume at the upper end can be formed, compared to cases outside the aforementioned range.

[0060] The biodegradable polymer material of the base structural layer can be at least one selected from the group consisting of hyaluronic acid and carboxymethylcellulose. In this case, the adhesion between the base structural layer and the drug-carrying layer containing semaglutide is superior compared to when different polymer materials are used.

[0061] The maximum width of the base structural layer may be between 800 μm and 1,400 μm. The maximum width refers to the diameter of the bottom surface of the formed base structural layer (see Figure 4).

[0062] If the maximum width of the base structural layer is less than 800 μm, the small surface area of ​​the bottom of the base structural layer may reduce the adhesive force between the support on which the microneedles are formed and the base structural layer, or the small surface area of ​​the top of the base structural layer may reduce the amount of semaglutide loaded in the drug-carrying layer formed on the base structural layer. If the maximum width of the base structural layer is greater than 1,400 μm, the large surface area of ​​the bottom of the base structural layer may make it difficult for the microneedles to penetrate the skin.

[0063] The height of the base structural layer can be 150 μm to 250 μm (see Figure 4).

[0064] If the height of the base structural layer is less than 150 μm, semaglutide loaded at the lower end of the drug-loading layer may remain in the body without being delivered, resulting in loss. If the height of the base structural layer exceeds 250 μm, it is difficult to form the drug-loading layer on the base structural layer, and the amount of semaglutide loaded in the drug-loading layer can be reduced.

[0065] In one embodiment, the length of the microneedle can be 700 to 800 μm from the support on which the microneedle is formed. In this case, a sufficient amount of semaglutide can be carried within the microneedle, and since it does not affect nerve cells when applied to the skin, it does not induce pain.

[0066] In one embodiment, the diameter of the tip of the microneedle can be 50 to 90 μm. In this case, the microneedle can effectively penetrate the skin while carrying a sufficient amount of semaglutide.

[0067] In one embodiment, the strength of the microneedle can be 0.058 N or higher. In this case, when applied to the skin, the needle can effectively penetrate the skin without breaking or bending.

[0068] The microneedles of the present invention can maintain a strength suitable for skin penetration while having a high semaglutide content, and can deliver a sufficient amount of drug into the body even in small quantities. Furthermore, compared to self-injectable therapeutic drugs, the microneedles of the present invention reduce the risk of bleeding, infection, pain, and fear, making them easier for patients to take, and they can reduce medical waste because they are biodegradable in the body.

[0069] When the microneedle of the present invention includes a drug-carrying layer and a base structure layer disposed on the bottom surface of the drug-carrying layer, the amount of semaglutide residue is low, thus reducing the loss of semaglutide.

[0070] This invention provides a method for manufacturing microneedles.

[0071] The present invention provides a method for producing microneedles, which includes the step of dropping a first viscous composition comprising semaglutide and a biodegradable polymer onto a first support to form a drug-carrying layer. (Step S10 in Figure 2)

[0072] The step of forming the drug-bearing layer may include dropping the first viscous composition onto a plurality of spaced-apart locations on the first support, pulling the dropped first viscous composition, and drying the pulled first viscous composition. In this case, the step of cutting the dried first viscous composition may be further included. (Steps S11-S14 in Figure 3)

[0073] The step of pulling the first viscous composition can be performed by bringing the second support into contact with the dropped first viscous composition, and then separating the first support and the second support.

[0074] The first support can be selected from the group consisting of, for example, hyaluronic acid or a pharmaceutically acceptable salt thereof, carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, polylactic acid-glycolic acid, gelatin, collagen, chitosan, and mixtures thereof.

[0075] The second support is described in the same manner as described above for the first support.

[0076] The step of cutting the first viscous composition can be performed by further separating the first support and the second support, or by a skilled worker using appropriate equipment.

[0077] Since the first viscous composition is the same as the composition for manufacturing microneedles of the present invention described above, or the viscous composition for forming the drug-carrying layer of the microneedles described above, its description is omitted to avoid duplication.

[0078] The term "spotting" refers to dispensing the first viscous composition in the form of a drop-let. This spotting can be performed by a dispenser, specifically by an air jet dispenser.

[0079] The above process makes it possible to manufacture microneedles in which semaglutide is uniformly distributed throughout the entire structure. The microneedles manufactured by the above process can maintain a strength suitable for skin penetration while having a high semaglutide content, and can deliver a sufficient amount of drug into the body even in small quantities.

[0080] Furthermore, the method for manufacturing microneedles of the present invention may further include the step of dropping a second viscous composition comprising a biodegradable polymer onto the first support to form a base structural layer, before dropping the first viscous composition onto the first support. In this case, the first viscous composition is dropped onto the base structural layer.

[0081] If the process further includes the step of forming the base structural layer, the process can produce a microneedle that includes the base structural layer at its lower end and a drug-carrying layer formed on the base structural layer. The microneedle produced by the process has a low semaglutide residue, thus reducing the loss of semaglutide.

[0082] The step of forming the base structural layer may include dropping the second viscous composition onto a plurality of spaced-apart locations on the first support, and drying the dropped second viscous composition.

[0083] The step of dropping the second viscous composition can be carried out such that the base structural layer formed from the second viscous composition has a preferred maximum width and height. The preferred maximum width and height are the same as those described above for the base structural layer of the microneedle of the present invention.

[0084] The step of drying the second viscous composition can be carried out under conditions that prevent the upper end of the base structural layer formed from the second viscous composition from collapsing or becoming concave. For example, it can be carried out by air drying or under drying conditions that maintain low humidity (15% or less).

[0085] The second viscous composition may not contain a functional material, such as semaglutide.

[0086] Since the second viscous composition described above is the same as the viscous composition that forms the base structural layer of the microneedle of the present invention described above, its description will be omitted to avoid duplication.

[0087] As described above, the microneedles manufactured by the manufacturing method of the present invention can maintain a strength suitable for skin penetration while having a high semaglutide content, and can deliver a sufficient amount of drug into the body even in small quantities. Furthermore, the microneedles containing the drug-carrying layer and the base structure layer manufactured by the manufacturing method of the present invention have a low semaglutide residue content, thus reducing semaglutide loss.

[0088] The present invention will be described in detail below with reference to examples. [Examples]

[0089] 1. Manufacturing and evaluation of compositions for microneedle production. (1) Manufacturing of compositions for microneedle production

[0090] A composition for manufacturing microneedles was prepared by mixing the components listed in Table 1 below with 1% by weight of disodium hydrogen phosphate (Na2HPO4) and 0.2% by weight of NaOH (sodium hydroxide) at the corresponding content (by weight). The disodium hydrogen phosphate and sodium hydroxide were added to increase the solubility of semaglutide. The prepared composition for manufacturing microneedles will also be referred to below as the composition for manufacturing the drug-carrying layer. (HA: Hyaluronic acid, PVP: Polyvinylpyrrolidone, C: Chondroitin, HEC: Hydroxyethylcellulose, HPMC: Hydroxypropylmethylcellulose)

[0091] [Table 1]

[0092] (2) Evaluation of the physical properties of the composition for manufacturing microneedles

[0093] The microneedle manufacturing composition produced in 1-(1) above was left at room temperature for 1 hour, and then the state of the composition was observed. If the composition was uniformly mixed in a liquid state, it was described as "good"; if it hardened at room temperature, it was described as "hardened"; and if the components in the composition were in a phase-separated state, it was described as "phase separated".

[0094] When the microneedle manufacturing composition produced in 1 above is in a liquid state at room temperature, the viscosity (cP) of the composition at 25°C was measured using a Brookfield rotary automatic viscometer.

[0095] Subsequently, microneedles were manufactured using the liquid microneedle manufacturing composition according to the method described in item 3 below, and it was observed whether or not a pointed microneedle was formed. If a microneedle was formed, it was marked with "○", and if it was not formed, it was marked with "×".

[0096] The results of the physical property evaluation of the composition are shown in Table 2.

[0097] [Table 2]

[0098] 2. Manufacturing and evaluation of microneedles (1) 1-layer microneedle 1) Manufacturing of 1-layer microneedles The microneedle manufacturing compositions listed in Table 3 below were dropped onto a support and pulled, and then the pulled composition was dried by blowing air onto it. The dried and solidified microneedle manufacturing compositions were cut to form microneedles. The number of microneedles formed on the support is as shown in Table 3 below. The microneedles manufactured by this method are needles in which the drug is uniformly distributed throughout the entire needle structure and consist only of the drug-carrying layer. For convenience, needles of this form are referred to as 1 layer.

[0099] [Table 3]

[0100] 2) Evaluation of 1-layer microneedles The microneedles manufactured in item 2-(1)-1) above were observed with an optical microscope, and the length and tip diameter of the microneedles were measured. The measurement results are shown in Table 4 below.

[0101] The compressive strength of the three central microneedles was measured using a tensile and compression testing machine. The strength was repeatedly measured for six samples manufactured from the same composition, and the average strength value was calculated. The strengths of the microneedles are shown in Table 4 below.

[0102] [Table 4]

[0103] (2) 2-layer microneedle 1) Manufacturing of 2-layer microneedles To manufacture a microneedle (2-layer microneedle) further containing a base structure layer positioned on the bottom surface of the drug-carrying layer, a composition for manufacturing the base structure layer was prepared by mixing the components listed in Table 5 below in the corresponding amounts (weight %). (HA: Hyaluronic acid, CMC: Carboxymethylcellulose)

[0104] [Table 5]

[0105] Subsequently, a 2-layer microneedle was manufactured using the microneedle manufacturing composition (Table 1) produced in 1-(1) above and the base structure layer manufacturing composition (Table 5) above.

[0106] The base structure layer manufacturing compositions listed in Table 6 below were dropped onto multiple locations on a support, and then dried by blowing air at room temperature to form multiple base structure layers (each 1000 μm wide and 200 μm high). The number of base structure layers formed on the support is as shown in Table 6 below.

[0107] A microneedle manufacturing composition (forming a drug-carrying layer) described in Table 6 was dropped onto each of the base structural layers, and after being pulled, the pulled composition was dried by blowing air onto it. A 2-layer microneedle was manufactured by cutting the dried and solidified microneedle manufacturing composition to form a drug-carrying layer.

[0108] [Table 6]

[0109] 2) Evaluation of 2-layer microneedles The microneedles manufactured in item 2-(2)-1) above were observed with an optical microscope, and the length and tip diameter of the microneedles were measured. The measurement results are shown in Table 7 below.

[0110] The compressive strength of the three central microneedles was measured using a tensile and compression testing machine. The strength was repeatedly measured for six samples manufactured from the same composition, and the average strength value was calculated. The strengths of the microneedles are shown in Table 7 below.

[0111] [Table 7]

[0112] 3. Evaluation of the semaglutide PK profile and area under the curve per dose using microneedles. The area under the curve (AUC) per dose of microneedles 1layer-1 and 1layer-3 in Table 3 and 2layer-1 and 2layer-3 in Table 6 was evaluated.

[0113] Specifically, the microneedles were inserted into dehaired miniature pigs aged 8 to 13 months, and blood samples were collected at 0, 3, 6, 9, 18, 24, 30, 48, 72, 96, 120, 144, and 168 hours. The blood samples were centrifuged to obtain serum, which was then analyzed using LC / MS-MS (model: Triple Quad® 5500, Agilent Technology (LC)AB SCIEX(MS)) to detect the concentration of semaglutide in the blood.

[0114] The blood concentration of semaglutide, as a result of blood sampling time, was plotted on a coordinate plane with time on the x-axis and blood concentration on the y-axis to obtain a pharmacokinetics profile. The area under the curve for semaglutide was calculated by integrating the obtained PK profile, and the microneedle was evaluated by correcting for the amount of semaglutide administered to the miniature pigs (Figure 5).

[0115] The area under the curve represents the degree of biological absorption of a drug and reflects the total amount of active drug that reaches systemic circulation. As shown in Table 8 below, all of the 1-layer-1, 1-layer-3, 2-layer-1, and 2-layer-3 microneedles showed an area under the curve of 10,000 ng·h / mL or more, confirming that all of these needles have superior bioavailability. Due to the base structure layer formed at the lower end of the 2-layer microneedle, the 2-layer needle showed a relatively larger area under the curve per dose compared to the 1-layer needle.

[0116] [Table 8]

[0117] 4. Evaluation of semaglutide residue in microneedles The 1layer-2, 1layer-4, and 1layer-6 microneedles from Table 3 and the 2layer-2, 2layer-4, and 2layer-6 microneedles from Table 6 were attached to pig skin, removed after 8 hours, and the amount of semaglutide residue (%) remaining on the patch was evaluated.

[0118] Specifically, the microneedles were inserted into dehaired miniature pigs under 12 months of age, removed after 8 hours, and the patch application site was wiped with gauze. The semaglutide concentration was calculated by analyzing the removed patch and the microneedles together using HPLC (Agilent) (Table 9).

[0119] As shown in Table 9 below, the 2-layer type microneedle exhibited a relatively lower residue amount compared to the 1-layer type needle, due to the base structure layer formed at the lower end of the 2-layer type microneedle.

[0120] [Table 9]

Claims

1. A composition for manufacturing microneedles, comprising semaglutide and a biodegradable polymer.

2. The composition for manufacturing microneedles according to claim 1, wherein the biodegradable polymer substance is at least one selected from the group consisting of hyaluronic acid, polyvinylpyrrolidone, chondroitin, hydroxyethylcellulose, and hydroxypropylmethylcellulose.

3. The composition for manufacturing microneedles according to claim 1, wherein the weight ratio of semaglutide to biodegradable polymer is 1:1.1 to 2.

9.

4. Disodium hydrogen phosphate (Na ２ HPO ４ The microneedle manufacturing composition according to claim 1, comprising at least one selected from the group consisting of disodium phosphorate and NaOH (sodium hydroxide).

5. The composition for manufacturing microneedles according to claim 1, further comprising at least one selected from the group consisting of trehalose and dextran.

6. A microneedle comprising a drug-carrying layer comprising semaglutide and a biodegradable polymer.

7. The microneedle according to claim 6, wherein the biodegradable polymer material of the drug-carrying layer is at least one selected from the group consisting of hyaluronic acid, polyvinylpyrrolidone, chondroitin, hydroxyethylcellulose, and hydroxypropylmethylcellulose.

8. The microneedle according to claim 6, wherein the weight ratio of semaglutide to biodegradable polymer in the drug-carrying layer is 1:1.1 to 2.

9.

9. The microneedle according to claim 6, further comprising a base structural layer disposed on the bottom surface of the drug-carrying layer and containing a biodegradable polymer substance.

10. The microneedle according to claim 9, wherein the base structural layer is formed from a viscous composition comprising a biodegradable polymer and water.

11. The microneedle according to claim 10, wherein the biodegradable polymer substance in the viscous composition is contained in an amount of 8 to 15% by weight relative to the total weight of the viscous composition.

12. The microneedle according to claim 9, wherein the biodegradable polymer material of the base structural layer is at least one selected from the group consisting of hyaluronic acid and carboxymethylcellulose.

13. A method for producing a microneedle, comprising the step of dropping a first viscous composition comprising semaglutide and a biodegradable polymer onto a first support to form a drug-carrying layer.

14. The method for producing a microneedle according to claim 13, wherein the step of forming the drug-carrying layer includes dropping the first viscous composition onto a plurality of spaced-apart locations on the first support, stretching the dropped first viscous composition, and drying the stretched first viscous composition.

15. The method for manufacturing a microneedle according to claim 14, wherein the step of pulling the first viscous composition is performed by bringing the second support into contact with the dropped first viscous composition, and then separating the first support and the second support.

16. The method for producing a microneedle according to claim 14, wherein the step of forming the drug-carrying layer further comprises the step of cutting the dried first viscous composition.

17. The method for producing microneedles according to claim 13, wherein the biodegradable polymer substance of the first viscous composition is at least one selected from the group consisting of hyaluronic acid, polyvinylpyrrolidone, chondroitin, hydroxyethylcellulose, and hydroxypropylmethylcellulose.

18. The method for producing microneedles according to claim 13, wherein the weight ratio of semaglutide to biodegradable polymer in the first viscous composition is 1:1.1 to 2.

9.

19. The process further includes the step of dropping a second viscous composition, comprising a biodegradable polymer, onto the first support to form a base structural layer, before dropping the first viscous composition onto the first support. The method for producing a microneedle according to claim 13, wherein the first viscous composition is dropped onto the base structural layer.

20. The method for producing a microneedle according to claim 19, wherein the step of forming the base structural layer includes dropping the second viscous composition onto a plurality of spaced-apart locations on the first support, and drying the dropped second viscous composition.

21. The method for producing microneedles according to claim 19, wherein the second viscous composition comprises a biodegradable polymer and water.

22. The method for producing microneedles according to claim 21, wherein the biodegradable polymer substance of the second viscous composition is contained in an amount of 8 to 15% by weight relative to the total weight of the second viscous composition.

23. The method for producing microneedles according to claim 19, wherein the biodegradable polymer substance of the second viscous composition is at least one selected from the group consisting of hyaluronic acid and carboxymethylcellulose.

Images