Method for manufacturing micro-spicules by using compression process

Abstract

The present invention relates to a method for manufacturing micro-spicules by using a compression process. When the method for manufacturing micro-spicules of the present invention is used, micro-spicules having a uniform shape can be effectively mass-produced.

Description

Method for manufacturing microspicules using a compression process

[0001] This patent application claims priority to Republic of Korea Patent Application No. 10-2024-0074394, filed with the Korean Intellectual Property Office on June 7, 2024, the disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a method for manufacturing microspicules using a compression process.

[0003] Microneedle arrays can be used as a method for applying functional ingredients to the skin. Compared to conventional packs or patches, microneedle arrays offer the advantage of more effectively delivering active ingredients into the skin. However, microneedles can only be applied to a limited area where a patch can be applied, and they are limited in that they can only be provided in the form of a cosmetic composition containing other liquid or semi-solid ingredients.

[0004] Microspicules generally have particle sizes ranging from several micrometers to several hundred micrometers, and are characterized by the formation of microscopic needles on their surface that can penetrate the skin. Microspicules have the advantage of being incorporated into cosmetic compositions.

[0005] Since microspicules are not provided in a form attached to a patch or the like, a process of separating individual microspicule particles from the base layer is necessary during the manufacturing process. For example, Korean Patent No. 10-2504373 discloses a method for manufacturing microneedle particles, and discloses a process for separating microneedle particles from a particle assembly in which the microneedle particles are formed.

[0006] However, in the case of the above-described process, a particle assembly material to which microneedle particles can be attached and formed is separately required, and an additional process is inevitably required, which causes the manufacturing of microneedle particles to become cumbersome.

[0007]

[0008] The present invention has been devised to solve the above-described problems, and provides a manufacturing method capable of effectively mass-producing microspicules.

[0009] The inventors of the present invention have diligently researched and developed a method for mass-producing microspicules of consistent shape through a continuous process. As a result, they discovered that the aforementioned problems can be solved by utilizing a compression mold in which microspicule units are continuously connected to form a negative shape. This led to the completion of the present invention.

[0010] Accordingly, an object of the present invention is to provide a method for producing microspicules suitable for mass production processes.

[0011] According to one aspect of the present invention, the present invention provides a method for producing microspicules comprising the following steps:

[0012] (a) A step of forming a polymer fabric by continuously discharging a biocompatible polymer material in one direction;

[0013] (b) a step of compressing a polymer fabric continuously discharged in one direction with a pair of compression molds consisting of an upper mold and a lower mold to form a microspicule complex having a shape in which microspicule units are continuously connected; and

[0014] (c) A step of producing microspicules by cutting the above microspicule complex into unit units.

[0015]

[0016] The inventors of the present invention have conducted extensive research to develop a method for mass-producing microspicules of consistent shape through a continuous process. As a result, they have discovered that the aforementioned problems can be solved by utilizing a compression mold in which microspicule units are continuously connected to form a negative shape.

[0017] In one embodiment of the present invention, the polymer fabric continuously discharged in step (a) is (i) a biocompatible polymer yarn having a circular cross-section with a diameter of 50 μm to 1000 μm or (ii) a polymer flat fabric with a thickness of 50 μm to 1000 μm.

[0018] In one embodiment of the present invention, the polymer fabric produced in step (a) may have part or all of its surface coated with a release paper.

[0019] In one embodiment of the present invention, at least one of the upper mold and the lower mold is formed with a negative mold.

[0020] In one embodiment of the present invention, the upper mold and the lower mold are roller-shaped.

[0021] In one embodiment of the present invention, the shape of the microspicule unit is a shape having one or more pointed portions.

[0022] In one embodiment of the present invention, the maximum diameter of the microspicule units is 50 μm to 2000 μm.

[0023] In one embodiment of the present invention, the unidirectional continuous discharge in step (a) may be by a piston or screw within a cylinder.

[0024] In one embodiment of the present invention, the biocompatible polymer material is hyaluronic acid (HA), poly(lactic acid; PLA), poly(ε-caprolactone; PCL), polyhydroxyalkanoate (PHA), polyesteramide (PEA), polyethylene glycol (PEG), poly(p-dioxanone; PPDO), poly(lactic-co-glycolic acid; PLGA), polyglycolic acid (PGA), polyvinyl alcohol (PVA), chitosan, collagen, gelatin, alginic acid, pectin, carrageenan, Chondroitin sulfate, dextran sulfate, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyvinylpyrrolidone (PVP);Hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, gum arabic, cyclodextrin, dextrin, glucose, fructose, starch, trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, polyglycolic acid, polyethylene oxide, A biocompatible biodegradable polymer material selected from the group consisting of polyacrylic acid, polyacrylamide, polymethacrylic acid, and polymaleic acid.

[0025] In one embodiment of the present invention, the microspicules may additionally contain a cargo material for delivery into the body.

[0026] In one embodiment of the present invention, the cargo material may be at least one selected from the group consisting of low molecular weight compounds, peptides, proteins, nucleic acids, polysaccharides, viruses, and liposomes.

[0027] The features and advantages of the present invention are summarized as follows:

[0028] (a) The present invention provides a method for producing microspicules suitable for mass production processes.

[0029] (b) When the microspicule manufacturing method of the present invention is used, microspicules of consistent shape can be effectively mass-produced.

[0030] Figure 1 shows a schematic diagram of a manufacturing device for implementing one embodiment of the present invention.

[0031] Fig. 2 shows a plan view of an example of the shape of the mold frame of the present invention, and shows that a negative mold in the shape of a square pyramid is formed at the center of the plane of the mold frame.

[0032] Fig. 3 shows a vertical cross-sectional view of a pair of molds, each comprising an upper mold and a lower mold, each having an example of the mold shape shown in Fig. 2. The hatched portion represents a cross-section, and shows that a pyramid-shaped negative mold is formed on each of the upper mold and the lower mold, and each of the pyramid molds is connected by a mold portion forming a connecting portion.

[0033] Fig. 4 shows an example of a cylindrical mold. The hatched portion represents a cross-section.

[0034] Figure 5 shows a perspective view of the cylindrical mold shown in Figure 4.

[0035]

[0036] Hereinafter, with reference to the attached drawings, embodiments of the method for manufacturing microspicules of the present invention will be described in detail so that those skilled in the art can easily practice the present invention. The terms used in this specification have been selected from widely used general terms as much as possible while considering the functions of the present invention, but these may vary depending on the intention of engineers working in the relevant field, precedents, the emergence of new technologies, etc. Unless otherwise defined, the technical and scientific terms used may have the meaning commonly understood by those skilled in the art to which this invention pertains.

[0037] As used herein and in the appended claims, the singular expression "singular" includes the plural expression unless the context clearly dictates otherwise. Furthermore, the plural expression "singular" includes the singular expression unless the context clearly dictates otherwise.

[0038] In this specification and the appended claims, the terms “include” or “have” mean that a feature or component described in the specification is present, and unless specifically limited, does not preclude the possibility that one or more other features or components may be added.

[0039] Additionally, the numerical ranges used herein include lower and upper limits and all values ​​within that range, increments logically derived from the shape and width of the defined range, all doubly defined values, and all possible combinations of upper and lower limits of numerical ranges defined in different shapes. Unless otherwise specifically defined in the specification of the present invention, values ​​outside the numerical range that may arise due to experimental error or rounding of values ​​are also included in the defined numerical range.

[0040] The term “about” or the like used in this specification and the appended claims is used to encompass the tolerance when an tolerance exists.

[0041] The term “biocompatibility” as used herein means the property of being substantially non-toxic, chemically inert and non-immunogenic to the human body.

[0042] The term “biodegradability” in this specification refers to the property of being self-decomposed in response to environmental factors within the human body, such as temperature, moisture, and microorganisms.

[0043] The term “microspicule” in this specification means a particle in which individual microspicule unit particles are independently separated, having a maximum diameter of several micrometers to several thousand micrometers, having one or more tips capable of penetrating the skin, and being applicable by incorporation into a liquid or semi-solid composition that can be applied to the skin.

[0044] The term “polymer material” in this specification refers to polymer yarn or polymer sheet in a state that is easy to press into a mold using a biocompatible polymer material as a raw material for manufacturing microspicules.

[0045] “Spicule” as a cosmetic raw material is generally derived from the spicule of the bony sponge, a class of freshwater sponges, and refers to a natural woody substance composed of calcium carbonate, silicate, and collagen in the form of micro-needle-like particles. However, “microspicule” in this specification refers to a microparticle artificially manufactured with a biocompatible polymer material having a shape similar to that of a natural spicule.

[0046] As a similar concept, in the case of “microneedles,” a plurality of microneedles are generally provided in the form of a “microneedle array” so that they can be attached to the skin through a patch or the like, but in the case of the “microspicule” of the present invention, as described above, they are provided in a state that can be mixed into a liquid or semi-solid composition.

[0047] A method for manufacturing microspicules according to one embodiment of the present invention can be performed using a device as shown in FIG. 1.

[0048] A method for manufacturing microspicules according to one embodiment of the present invention is characterized in that, as illustrated in FIG. 1, microspicule units are continuously connected through a mold (107) to form a microspicule complex of a combined shape, and then the microspicules are manufactured by cutting them using a cutting portion (108) or other means.

[0049] A biocompatible polymer material is injected through a raw material inlet (101), and a biocompatible polymer fabric is continuously discharged through an outlet, thereby forming a microspicule complex through a pair of mold frames (107) including an upper mold frame and a lower mold frame. By forming a microspicule complex, the microspicule complex can be easily separated from the mold frame (107), facilitated transportation, and minimized loss of raw material. There may be one or more outlets, and by appropriately controlling the number of outlets and appropriately controlling the shape or number of mold frames (107), the production amount of microspicules per unit time can be controlled as much as possible.

[0050] The polymer fabric continuously discharged through the outlet may be, but is not limited to, (i) a biocompatible polymer yarn having a circular cross-section with a diameter of 50 μm to 1000 μm or (ii) a polymer sheet having a thickness of 50 μm to 1000 μm.

[0051] In one embodiment of the present invention, the polymer fabric may have a part or all of its surface coated with a release layer. When the polymer fabric is in the form of a polymer sheet, the release layer may be attached to the upper and / or lower portions of a biocompatible polymer layer. When the polymer fabric is in the form of a polymer yarn, the surface of the yarn may be coated with the release layer. The release layer in the present specification is not particularly limited, and may be a layer of a biocompatible polymer material different from the biocompatible polymer material constituting the core, may be an effective material for delivery to the skin, and may be a release film layer for ensuring the stability of storage and distribution of microspicules, specifically, may be, for example, a PET film, a fluorine-coated paper, etc., but is not necessarily limited thereto.

[0052] As shown in Fig. 1, the method for manufacturing microspicules of the present invention is carried out by pressing a polymer fabric using a mold (107), and the mold (107) of the present invention may be composed of a pair of upper molds and lower molds. At least one of the upper molds and the lower molds has a negative mold formed therein. Figs. 2 and 3 illustrate examples of molds that press a polymer fabric through up-and-down reciprocating motion. Fig. 2 illustrates a plan view of the mold, and illustrates a mold in which a negative mold in the shape of a square pyramid is formed. When pressing a polymer fabric using a pair of the molds and a flat mold in which a negative mold is not formed, a microspicule in the shape of a square pyramid can be manufactured. In addition, when pressing a polymer fabric together with an additional mold in which an negative mold in the shape of the same square pyramid is formed, an octahedral microspicule can be manufactured. In this way, the shape of the negative mold of the mold frame can be freely adjusted to control the shape of the microspicule. However, the shape of the negative mold is not necessarily limited to the embodiment, and a variety of negative molds of a shape suitable for providing microspicules can be applied.

[0053] Fig. 3 shows a vertical cross-section of a mold in an embodiment in which a negative mold is formed on both the upper mold and the lower mold, and the hatched portion shows a vertically cut portion.

[0054] As shown in FIGS. 4 and 5, the mold (107) may have a cylindrical shape capable of pressing a polymer fabric through a rotational motion.

[0055] The shape of the microspicule unit of the present invention is a shape having one or more pointed ends. The aforementioned pointed ends enable easy absorption into the skin. Unlike the conventional microneedle arrays having the characteristic of having pointed ends arranged in one direction, the microspicule of the present invention can be mixed into a liquid or semi-solid composition and applied to the skin, and therefore, it is preferable to have multiple pointed ends. Accordingly, it is preferable to manufacture a shape having multiple pointed ends, such as a polyhedral shape or a polyhedral shape. Specifically, for example, the shape of the microspicule unit of the present invention may be a tetrahedron, a pentahedron, a hexahedron, a heptahedron, an octahedron, a cone, a bell tower, etc., and the apex of each shape may be adjusted to a sharp shape having a smaller acute angle so as to be particularly advantageous for penetrating the skin.

[0056] The maximum diameter of the microspicule unit manufactured according to one embodiment of the present invention may be 50 μm to 2000 μm, but is not particularly limited thereto. In other specific embodiments, the microspicule of the present invention may have a maximum diameter of 50 μm to 1500 μm, 50 μm to 1000 μm, 50 μm to 800 μm, or 100 μm to 800 μm. The microspicule may be manufactured by appropriately selecting the maximum diameter of the microspicule depending on the physical properties of the raw material for manufacturing the microspicule, whether or not an effective raw material is mixed therein, etc.

[0057] As shown in Fig. 1, the biocompatible polymer material of the present invention is injected into a cylinder (102) through a raw material injection port (101), and the injected polymer material is heated and can be deformed into a state that is easy to mold. Specifically, for example, the cylinder (102) may be a heating cylinder including a heater (104), and the injected polymer material may be heated, moved toward an outlet by a means such as a screw (103) or a piston, and molded and discharged through the outlet.

[0058] That is, in one embodiment of the present invention, the continuous discharge of the biocompatible polymer material in one direction in step (a) may be by a piston or screw within the cylinder.

[0059] The biocompatible polymer material of the present invention is hyaluronic acid (HA), poly(lactic acid; PLA), poly(ε-caprolactone; PCL), polyhydroxyalkanoate (PHA), polyesteramide (PEA), polyethylene glycol (PEG), poly(p-dioxanone; PPDO), poly(lactic-co-glycolic acid; PLGA), polyglycolic acid (PGA), polyvinyl alcohol (PVA), chitosan, collagen, gelatin, alginic acid, pectin, carrageenan, chondroitin sulfate, Dextran sulfate, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyvinylpyrrolidone (PVP);Hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, gum arabic, cyclodextrin, dextrin, glucose, fructose, starch, trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, polyglycolic acid, polyethylene oxide, It may be at least one selected from the group consisting of polyacrylic acid, polyacrylamide, polymethacrylic acid, and polymaleic acid.;

[0060] According to one embodiment of the present invention, the microspicules of the present invention may additionally include a cargo material for delivery into the body.

[0061] The term “cargo” in the present embodiment refers to a biocompatible material suitable for injection into a living body, and is an effective material expected to exhibit a desired effect by the user, and is not particularly limited. Specifically, for example, the cargo material may be at least one selected from the group consisting of low-molecular-weight compounds, peptides, proteins, nucleic acids, polysaccharides, viruses, and liposomes. The above-mentioned nucleic acids may include oligonucleotides, plasmid DNA, siRNA, PNAs (peptide nucleic acids), etc. Specifically, for example, the cargo material of the present invention may be selected without limitation from conventionally known pharmaceutical compositions or functional cosmetic compositions. Specifically, for example, the low-molecular-weight compound may be various effective ingredients for skin beauty or topical application to the skin, and specifically, for example, may be an antioxidant such as vitamin C or vitamin E, or a functional material having a skin whitening, wrinkle improvement, or acne prevention or treatment effect.

[0062] As shown in Fig. 1, the polymer fabric discharged through the discharge port can be cooled through a cooling unit (105). This allows the polymer fabric to be moved while maintaining its yarn or sheet shape.

[0063] The polymer fabric can be continuously moved through one or more receiving devices (106). The receiving device (106) can be, for example, a device having a moving floor surface, and can be, for example, in the shape of a conveyor belt, and can be, but is not necessarily limited to, a conveyor belt having an upper and lower portions in contact with each other.

[0064] According to one embodiment of the present invention, the mold may have a flat shape that can be pressed by up-and-down movement as described above, or may have a cylindrical shape that can be pressed by rotational movement. The microspicule complex formed by the pressing mold may be cut into individual microspicule units through a cutting process. The cutting process described above may be performed using a sharp blade, and since the portion where the microspicule unit and another unit are connected has a smaller diameter than the other portions, it can be relatively easily broken by the application of an external force, and thus, by applying a predetermined external force to the microspicule complex, it can be separated into individual microspicule units. The predetermined external force described above may be, for example, a force generated by vibration from a shaker.

[0065]

[0066] Description of the symbol

[0067] 100: Microspicule manufacturing device

[0068] 101: Raw material inlet

[0069] 102: Cylinder

[0070] 103: Screw

[0071] 104: Heater

[0072] 105: Cooling section

[0073] 106: Takeover device

[0074] 107: Mold

[0075] 108: Cut section

Claims

1. A method for manufacturing microspicules comprising the following steps: (a) A step of forming a polymer fabric by continuously discharging a biocompatible polymer material in one direction; (b) a step of compressing a polymer fabric continuously discharged in one direction with a pair of compression molds consisting of an upper mold and a lower mold to form a microspicule complex having a shape in which microspicule units are continuously connected; and (c) A step of producing microspicules by cutting the above microspicule complex into unit units.

2. In paragraph 1, A method for producing microspicules, characterized in that the polymer fabric continuously discharged in the above step (a) is (i) a biocompatible polymer yarn having a circular cross-section with a diameter of 50 μm to 1000 μm or (ii) a polymer sheet having a thickness of 50 μm to 1000 μm.

3. In paragraph 1, A method for manufacturing microspicules, characterized in that the polymer fabric produced in the above step (a) is in a state in which part or all of the surface is coated with a heteromorphic layer.

4. In paragraph 1, A method for manufacturing microspicules, characterized in that at least one of the upper mold and the lower mold is formed with a negative mold.

5. In paragraph 4, A method for manufacturing microspicules, characterized in that the upper mold and the lower mold have a cylindrical shape.

6. In paragraph 1, A method for manufacturing microspicules, characterized in that the shape of the above microspicule units is a shape having one or more cutting edges.

7. In paragraph 6, A method for manufacturing microspicules, characterized in that the maximum diameter of the microspicule units is 50 μm to 2000 μm.

8. In paragraph 1, A method for producing microspicules, characterized in that the continuous discharge in one direction in the above step (a) is by a piston or screw within a cylinder.

9. In paragraph 1, The biocompatible polymer materials include hyaluronic acid (HA), poly(lactic acid; PLA), poly(ε-caprolactone; PCL), polyhydroxyalkanoate (PHA), polyesteramide (PEA), polyethylene glycol (PEG), poly(p-dioxanone; PPDO), poly(lactic-co-glycolic acid; PLGA), polyglycolic acid (PGA), polyvinyl alcohol (PVA), chitosan, collagen, gelatin, alginic acid, pectin, carrageenan, chondroitin sulfate, Dextran sulfate, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyvinylpyrrolidone (PVP);Hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, gum arabic, cyclodextrin, dextrin, glucose, fructose, starch, trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, polyglycolic acid, polyethylene oxide, A method for manufacturing microspicules, characterized in that the microspicules are made of at least one biocompatible biodegradable polymer material selected from the group consisting of polyacrylic acid, polyacrylamide, polymethacrylic acid, and polymaleic acid.

10. In paragraph 9, A method for manufacturing microspicules, characterized in that the microspicules additionally contain a cargo material for delivery into the body.

11. In paragraph 10, A method for producing microspicules, wherein the cargo material is at least one selected from the group consisting of low molecular weight compounds, peptides, proteins, nucleic acids, polysaccharides, viruses, and liposomes.

Images