Freeze-drying mold and method for preparing water-soluble polymer spheres using the same

Abstract

The present invention relates to a freeze-drying mold and a method for preparing a water-soluble polymer sphere using the same. More specifically, the present invention relates to the following freeze-drying mold and a method for preparing a water-soluble polymer sphere using the same. The freeze-drying mold is characterized in that it includes: a first mold, a plurality of first receiving grooves are formed on the bottom surface, and a discharge portion is formed on the upper surface, so that the first receiving grooves can be communicated with the first receiving grooves respectively; and a second mold, a plurality of second receiving grooves are formed on the upper surface, and the second receiving grooves are combined with the first mold facing each other so that the first receiving grooves and the second receiving grooves form a receiving portion. According to the present invention, the following effects are achieved: a freeze-drying mold is provided, and the shrinkage rate of the solution is adjusted during freeze drying, so as to prepare a spherical freeze-dried product, and the prepared freeze-dried product is easy to fall off from the mold, and the drying efficiency is maximized, and a method for preparing water-soluble polymer spheres with constant pore size and distribution, high strength, and no film formed on the surface using the freeze-drying mold is provided.

Description

Technical Field

[0001] The present invention relates to a freeze-drying mold and a method for preparing water-soluble polymer spheres using the same. More specifically, the present invention relates to a freeze-drying mold in which the shrinkage rate of a solution is adjusted during freeze-drying, thereby preparing spherical freeze-dried products, the prepared freeze-dried products are easy to fall off the mold, and the drying efficiency is maximized. The present invention also relates to a method for preparing water-soluble polymer spheres having constant pore size and distribution, high strength, and no film formed on the surface using the freeze-drying mold. Background Art

[0002] Hyaluronic acid, a water-soluble polymer, is a polysaccharide composed of linearly linked repeating units of N-acetylglucosamine and D-glucuronic acid. It is a biopolymer known to be present in large quantities in the placenta, synovial fluid, pleural fluid, skin, and combs of roosters of animals since it was first isolated from the fluid filling the eyeballs of animals [Meyer K. et al., Journal of Biology and Chemistry 107629-34 (1934)]. It is also produced in microorganisms of the genus Streptococcus such as Streptococcus equi and Streptococcus zooepidemecus.

[0003] Hyaluronic acid is not only used for cosmetic purposes such as cosmetic additives, but also widely used in multiple medical applications such as ophthalmic surgical adjuvants, joint function improvers, drug delivery materials and eye drops due to its excellent biocompatibility and high viscoelastic properties under solution state. However, it is only easily decomposed under the conditions of hyaluronic acid itself in vivo (invivo) or acid, alkali, etc., so its use is limited. Therefore, many researches (Laurent, TC, et al., Portland Press Ltd, London, 1998) of hyaluronic acid derivatives that are stable on the structure are being developed by the method for cross-linking or attaching functional groups of hyaluronic acid.

[0004] Furthermore, it is known that as an attempt to change the physicochemical properties and biological properties of hyaluronic acid for the above-mentioned various uses, hyaluronic acid is prepared into a sponge form in order to be used as a support for the purpose of cell or tissue culture and transplantation or a carrier of a drug delivery system, a wound covering material, a dental material, a cosmetic material, and a medical material.

[0005] However, when hyaluronic acid is prepared into a sponge form, the shrinkage rate varies depending on the position of the mold, thereby producing an asymmetric product. After preparation, it is not easy to fall off the mold, thereby reducing the recovery rate, causing difficulties in the process, and the strength is also low, and a thin film is formed on the surface, thereby hindering the physical properties or applications of hyaluronic acid.

[0006] [Prior art literature]

[0007] [Patent Document]

[0008] (Patent Document 1) Korean Patent No. 2010-0079363 Summary of the invention

[0009] Technical issues

[0010] In order to solve the problems of the prior art as described above, the object of the present invention is to provide a freeze-drying mold as follows, in which the shrinkage rate of the solution is adjusted during freeze-drying, thereby preparing spherical freeze-dried products, and the prepared freeze-dried products are easy to fall off the mold and the drying efficiency is maximized. In addition, a method for preparing water-soluble polymer spheres with constant pore size and distribution, high strength and no film formed on the surface using the above-mentioned freeze-drying mold is provided.

[0011] The above-mentioned object and other objects of the present invention can be achieved by the present invention described below.

[0012] Technical solutions to the problem

[0013] In order to achieve the above-mentioned purpose, the present invention provides a freeze-drying mold, characterized in that it includes: a first mold, having a plurality of first receiving grooves formed on the bottom surface, and a discharge portion formed on the upper surface so as to be respectively connected with the above-mentioned first receiving grooves; and a second mold, having a plurality of second receiving grooves formed on the upper surface, which is combined with the above-mentioned first mold facing each other so that the above-mentioned first receiving grooves and the second receiving grooves form a receiving portion.

[0014] Furthermore, the present invention provides a freeze-drying mold, characterized in that it comprises: a first mold, on the bottom surface of which an insertion portion is protruded in a step-forming manner, a plurality of hemispherical first receiving grooves are formed in a lattice form on the surface of the insertion portion, and a discharge portion is formed on the upper surface so as to be respectively connected with the first receiving grooves; and a second mold, on the upper surface of which a recessed insertion groove is formed so as to be combined with the insertion portion, a plurality of hemispherical second receiving grooves are formed in a lattice form on the inner surface of the insertion groove, and through combination with the first mold, the first receiving groove and the second receiving groove form a spherical receiving portion, wherein more than one consistent fastening holes are formed in the first mold and the second mold so that they can be fastened by a fastening component.

[0015] In addition, the present invention provides a method for preparing water-soluble polymer balls, which is characterized in that it includes: a step of combining a first mold and a second mold, wherein a plurality of first receiving grooves are formed on the bottom surface of the first mold, and a discharge portion is formed on the upper surface so as to be respectively connected to the first receiving grooves, and a plurality of second receiving grooves are formed on the upper surface of the second mold, which are combined with the first mold facing each other so that the first receiving grooves and the second receiving grooves form a receiving portion; a step of freeze-drying a water-soluble polymer solution; and a step of separating the combined first mold and second mold to obtain water-soluble polymer balls, wherein the water-soluble polymer solution is supplied to the second mold before the first mold and the second mold are combined or supplied to the receiving portion through the discharge portion after the above-mentioned combination.

[0016] Effects of the Invention

[0017] The present invention has the following effects: providing a freeze-drying mold, in which the shrinkage rate of the solution is adjusted during freeze-drying, thereby preparing a desired shape, especially preparing a spherical freeze-dried product, and the prepared freeze-dried product is easy to fall off the mold and the drying efficiency is maximized. In addition, a method for preparing water-soluble polymer spheres with constant pore size and distribution, high strength and no film formed on the surface using the above-mentioned freeze-drying mold is provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 It is a perspective view showing the bottom surface of the first mold of the present invention.

[0019] Figure 2 It is a top view showing the upper surface of the first mold of the present invention.

[0020] Figure 3 It is a top view showing the bottom surface of the first mold of the present invention.

[0021] Figure 4 It is a side view showing the side surface of the first mold of the present invention.

[0022] Figure 5 It is a cross-sectional view showing a cross section of the first mold of the present invention.

[0023] Figure 6 It is a perspective view showing the upper surface of the second mold of the present invention.

[0024] Figure 7 It is a top view showing the upper surface of the second mold of the present invention.

[0025] Figure 8 It is a side view showing the side surface of the second mold of the present invention.

[0026] Fig. 9It is a cross-sectional view showing a cross section of the second mold of the present invention.

[0027] Fig.10 It is a cross-sectional view showing the cross section of a freeze-drying mold formed by inserting and combining the first mold and the second mold of the present invention.

[0028] Fig.11 The photographs are taken of the hyaluronic acid-based composition spheres prepared in Example 1, Comparative Examples 1 to 7 and Reference Example 1, respectively.

[0029] Fig.12 and Fig.13 The photographs are taken of the remaining state after the hyaluronic acid-based composition spheres were respectively recovered from the mold after freeze drying in Example 1, Comparative Examples 1 to 7 and Reference Example 1. Among them, the photograph of the lower end of the mold is a photograph of the recovered hyaluronic acid-based composition spheres. DETAILED DESCRIPTION

[0030] Hereinafter, the freeze-drying mold of the present invention and the method for producing water-soluble polymer spheres using the same will be described in detail.

[0031] The present inventors have confirmed that when a pair of positive and negative molds formed by a lower mold and an upper mold are used, and the structures and thermal conductivity of the lower mold and the upper mold are adjusted to a specified range, if a hyaluronic acid-based composition solution as a water-soluble polymer solution is freeze-dried, the shrinkage rate is adjusted, thereby preparing a freeze-dried product in the desired shape, that is, the same shape as the cavity. The freeze-dried product prepared in this way also has excellent effects such as constant pore size and distribution, high strength, and no film is formed on the surface. Based on this, the inventors conducted more diligent research and completed the present invention.

[0032] The freeze-drying mold of the present invention is characterized in that it includes: a first mold, a plurality of first receiving grooves are formed on the bottom surface, and a discharge portion is formed on the upper surface so that they can be connected to the first receiving grooves respectively; and a second mold, a plurality of second receiving grooves are formed on the upper surface, and the second mold is combined with the first mold facing each other so that the first receiving groove and the second receiving groove form a receiving portion. In this case, there is an advantage that the freeze-dried product of the desired shape can be easily and quickly obtained.

[0033] As an example, the first receiving groove and the second receiving groove are respectively hemispherical. Through the combination of the first receiving groove and the second receiving groove, the receiving portion can be spherical. In this case, it has the advantages of easy handling or high utilization of the freeze-dried material.

[0034] As an example, the diameter of the above-mentioned receiving portion can be 5 to 30 mm, preferably 5 to 25 mm, more preferably 10 to 20 mm, and further preferably 10 to 15 mm. Within this range, the freeze-dried product has the advantages of easy handling or high utilization as a cosmetic material, etc.

[0035] Preferably, the first storage tank and the second storage tank may be arranged in a grid form. In this case, there is an effect that the freeze-dried product can be easily handled or the productivity is excellent.

[0036] As a preferred example, an insertion portion is protruded on the bottom surface of the above-mentioned first mold in a step-forming manner, the above-mentioned first receiving groove is formed on the surface of the above-mentioned insertion portion, and a recessed insertion groove is formed on the upper surface of the above-mentioned second mold so that the above-mentioned insertion portion can be inserted and combined, and the above-mentioned second receiving groove can be formed on the inner surface of the above-mentioned insertion groove. In this case, it has the advantages of easy implementation of the freeze-drying process and subsequent easy processing of the freeze-dried product.

[0037] As an example, the size of the free space of the above-mentioned insertion groove can be the same as or larger than the size of the free space of the first receiving groove, preferably, it can be 1 to 2 times. Within this range, the freeze-drying process is easy to implement, the loss of the object solution is small, and the freeze-dried product of the desired shape is obtained.

[0038] As another example, the depth of the insertion groove may be the same as the depth of the first receiving groove or 1 to 2 times the depth of the first receiving groove. As a specific example, the depth of the insertion groove may be greater than the depth of the first receiving groove and may be 2.5 to 15 mm, preferably 5 to 12.5 mm, and more preferably 7.5 to 10 mm. Within this range, the freeze-drying process is easily implemented, the loss of the object solution is small, and the freeze-dried product of the desired shape is obtained.

[0039] Preferably, more than one consistent fastening holes can be formed in the above-mentioned first mold and the second mold, so that they can be fastened together by fastening components. More preferably, 1 to 5 fastening holes are formed. Within this range, there is the advantage of safely carrying out freeze-drying treatment and subsequently easily handling the freeze-dried product.

[0040] Preferably, the thermal conductivity of the first mold is lower than that of the second mold. More preferably, when the reference temperature is 20°C, the difference is more than 100 W / mK, more preferably more than 150 W / mK, further preferably more than 200 W / mK, and most preferably 200 to 250 W / mK. Within this range, the shrinkage rate of the freeze-dried solution is adjusted during freeze-drying to obtain the desired shape, that is, to obtain a freeze-dried product of the same shape as the mold cavity, and to maximize the drying efficiency.

[0041] In the present invention, when a thermal conductivity measurement method commonly used in the technical field to which the present invention belongs is used, the thermal conductivity is not particularly limited, but as a specific example, it can be measured by using a non-contact method according to ASTM E1461. When the above non-contact method is described in detail, the thermal diffusivity (α), specific heat (Cp), and density (ρ) are measured and then converted into thermal conductivity (λ), which has the advantage that the thermal conductivity can be considered according to the thickness (y) and horizontal (x) angular direction, and the measurement range is about 0.1 to 2000 W / m·K.

[0042] As an example, the first mold can be formed by including a thermoplastic resin, preferably, by including one or more selected from polyacetal resin and polyolefin resin, more preferably, by including polyacetal resin or polypropylene resin. In this case, the following effects are achieved: the drying efficiency during freeze-drying is excellent, the shrinkage rate of the object solution is adjusted, thereby obtaining a spherical freeze-dried product, the prepared freeze-dried product is easily removed from the mold, thereby maximizing the recovery rate, and providing a freeze-dried product with constant pore size and distribution, high strength, and no film formed on the surface.

[0043] As an example, the thermal conductivity of the thermoplastic resin under the conditions of 1 atmosphere and 293K is 100 W / mK or less, preferably 50 W / mK or less, more preferably 10 W / mK or less, further preferably 1 W / mK or less, and further preferably 0.01 to 1 W / mK. Within this range, the shrinkage rate of the freeze-dried solution is adjusted during freeze-drying to obtain the desired shape, that is, to obtain a freeze-dried product having the same shape as the mold cavity, and the drying efficiency is maximized.

[0044] Preferably, the second mold is formed by containing a metal, more preferably, by containing one or more metals selected from aluminum, duralumin, tungsten, iron, cast iron, carbon steel, stainless steel, copper, bronze, brass, lead, nickel, gold and silver, and further preferably, by containing aluminum. In this case, the second mold has the following effects: the drying efficiency during freeze-drying is excellent, the shrinkage rate of the target solution is adjusted to obtain a spherical freeze-dried product, the prepared freeze-dried product is easy to fall off the mold, so that the recovery rate is maximized, and a freeze-dried product with constant pore size and distribution, high strength and no film formed on the surface is provided.

[0045] As an example, the thermal conductivity of the metal under the conditions of 1 atmosphere and 293K is 200 W / mK or more, preferably 210 W / mK or more, more preferably 220 W / mK or more, further preferably 225 W / mK or more, and further preferably 225 to 250 W / mK. Within this range, the shrinkage rate of the freeze-dried solution is adjusted during freeze-drying to obtain the desired shape, that is, to obtain a freeze-dried product having the same shape as the mold cavity, and the drying efficiency is maximized.

[0046] As an example, the surface of the second mold can be anodized, preferably hard anodized, in which case the prepared freeze-dried product can easily fall off the mold, maximizing the recovery rate, and no film will be formed on the surface.

[0047] Preferably, the surface after the above-mentioned anodizing treatment can be sealed, colored, or both sealed and colored. More preferably, when sealing, it can be colored with a white pigment. In this case, the prepared freeze-dried product can easily fall off the mold, maximizing the recovery rate, and no film will be formed on the surface.

[0048] The anodizing treatment of the present invention is a process of converting a metal surface into aluminum oxide by electrical or chemical methods, and is not particularly limited when using a method commonly practiced in the technical field to which the present invention belongs.

[0049] The sealing treatment of the present invention is to make the thin film formed on the metal surface after the anodizing treatment smooth, and is not particularly limited when using a treatment method commonly implemented in the technical field to which the present invention belongs.

[0050] The coloring treatment of the present invention is to add a pigment during the sealing treatment to achieve gloss or a beautiful appearance, etc., and is not particularly limited when using a treatment method commonly practiced in the technical field to which the present invention belongs.

[0051] Preferably, the upper surface of the second mold may be coated with one or more selected from fluorinated resins and polyolefin resins. In this case, the prepared freeze-dried product can be easily removed from the mold, maximizing the recovery rate, and no film will be formed on the surface.

[0052] As an example, the fluorinated resin is one or more selected from polytetrafluoroethylene (PTFE), polychlorotrifluoroethylene (PCTFE), polyvinylidene fluoride (PVDF), polyvinyl fluoride (PVF), perfluoroalkoxy resin (PFA), tetrafluoroethylene-hexafluoropropylene copolymer (FEP), ethylene-tetrafluoroethylene copolymer (ETFE) and ethylene-chlorotrifluoroethylene copolymer (ECTFE). In this case, the prepared freeze-dried product can be easily removed from the mold, maximizing the recovery rate, and no film will be formed on the surface.

[0053] The coating may be performed by wet coating or dry coating commonly used in the technical field of the present invention without any particular limitation, but preferably, it may be dry coating in which the fluorinated resin powder is directly coated on the surface of the substrate by heat or plasma.

[0054] As an example, the polyolefin resin may be polypropylene, polyethylene or a mixture thereof. In this case, the prepared freeze-dried product can be easily removed from the mold to maximize the recovery rate, and no film is formed on the surface.

[0055] The freeze-drying mold of the present invention is characterized in that it includes: a first mold, an insertion portion is formed in a step-forming manner on the bottom surface, a plurality of hemispherical first receiving grooves are formed in a lattice form on the surface of the above-mentioned insertion portion, and a discharge portion is formed on the upper surface so as to be connected with the above-mentioned first receiving grooves respectively; and a second mold, a recessed insertion groove is formed on the upper surface so as to be combined with the above-mentioned insertion portion, and a plurality of hemispherical second receiving grooves are formed in a lattice form on the inner surface of the above-mentioned insertion groove, and through the combination with the above-mentioned first mold, the above-mentioned first receiving groove and the second receiving groove form a spherical receiving portion, wherein more than one consistent fastening hole is formed in the above-mentioned first mold and the second mold, so that they can be fastened by a fastening component. In this case, the following effect is achieved: when the water-soluble polymer solution is freeze-dried, its shrinkage rate is adjusted, so as to obtain a spherical dry water-soluble polymer, and the spherical dry water-soluble polymer is easy to fall off from the mold, so that the recovery rate is excellent, and the freeze-drying efficiency is maximized, and the pore size and distribution of the obtained water-soluble polymer spheres are constant and the strength is high.

[0056] Preferably, the freeze-drying mold may be a water-soluble polymer freeze-drying mold.

[0057] The method for preparing water-soluble polymer spheres of the present invention is characterized in that it includes: a step of combining a first mold and a second mold, wherein a plurality of first receiving grooves are formed on the bottom surface of the first mold, and a discharge portion is formed on the upper surface so as to be respectively connected to the first receiving grooves, and a plurality of second receiving grooves are formed on the upper surface of the second mold, and the first receiving grooves and the second receiving grooves are combined with the first mold in a facing direction so that the first receiving grooves and the second receiving grooves form a receiving portion; a step of freeze-drying a water-soluble polymer solution; and a step of separating the combined first mold and the second mold to obtain water-soluble polymer spheres, wherein the water-soluble polymer solution is supplied to the second mold before the first mold is combined with the second mold or supplied to the receiving portion through the discharge portion after the combination, and the thermal conductivity of the first mold is lower than that of the second mold. When the steps as described above are passed, the following advantages are obtained: the shrinkage rate of the solution is adjusted during freeze drying, thereby preparing a spherical freeze-dried product, the prepared freeze-dried product is easy to fall off from the mold, so that the recovery rate is maximized, and the freeze-drying efficiency is excellent, and the pore size and distribution of the prepared freeze-dried product are constant and the strength is high.

[0058] Preferably, the method for preparing the water-soluble polymer spheres is characterized in that it includes: step A), preparing a first mold and a second mold, wherein a plurality of first receiving grooves are formed on the bottom surface of the first mold, and a discharge portion is formed on the upper surface so as to be respectively connected to the first receiving grooves, and a plurality of second receiving grooves are formed on the upper surface of the second mold, and the second receiving grooves are combined with the first mold in a facing direction so that the first receiving grooves and the second receiving grooves form a receiving portion; step B), after supplying a water-soluble polymer solution to the second mold, the second mold is combined with the first mold; step C), freeze-drying the supplied water-soluble polymer solution; and step D), separating the combined first mold and the second mold to obtain water-soluble polymer spheres, wherein the thermal conductivity of the first mold is lower than that of the second mold. When the steps described above are performed, the following advantages are obtained: the shrinkage rate of the solution is adjusted during freeze drying, thereby preparing a spherical freeze-dried product, the prepared freeze-dried product is easy to fall off from the mold, so that the recovery rate is maximized, and the freeze-drying efficiency is excellent, and the pore size and distribution of the prepared freeze-dried product are constant and the strength is high.

[0059] Preferably, an insertion portion can be protruded on the bottom surface of the above-mentioned first mold in a step-forming manner, a plurality of hemispherical first receiving grooves are formed in a grid form on the surface of the above-mentioned insertion portion, and a discharge portion is formed on the upper surface so as to be respectively connected with the above-mentioned first receiving grooves.

[0060] Preferably, a recessed insertion groove can be formed on the upper surface of the above-mentioned second mold so that it can be combined with the above-mentioned insertion part, and a plurality of hemispherical second receiving grooves are formed in a grid form on the inner surface of the above-mentioned insertion groove. By combining with the above-mentioned first mold, the above-mentioned first receiving groove and the second receiving groove form a spherical receiving part.

[0061] After the freeze-drying solution is filled into the insertion groove of the above-mentioned second mold, when the first mold is combined on the second mold, the freeze-drying solution naturally fills the first receiving groove of the first mold, and the excess freeze-drying solution is discharged through the above-mentioned discharge part. Moreover, when freeze-drying, if the freeze-drying material expands or produces water, it can also be discharged or removed through the discharge part, thereby having the effect of easily realizing the freeze-drying process and obtaining the freeze-dried material of the desired shape.

[0062] Preferably, at least one consistent fastening hole is formed in the first mold and the second mold, so that they can be fastened together by a fastening component.

[0063] As an example, the method for preparing the water-soluble polymer spheres is characterized in that it includes: step a), combining a first mold and a second mold, forming a plurality of first receiving grooves on the bottom surface of the first mold, forming a discharge portion on the upper surface so as to be respectively connected to the first receiving grooves, forming a plurality of second receiving grooves on the upper surface of the second mold, and combining with the first mold in opposite directions so that the first receiving grooves and the second receiving grooves form a receiving part; step b), supplying a water-soluble polymer solution to the receiving part through the discharge portion; step c), freeze-drying the water-soluble polymer solution supplied to the receiving part; and step d), separating the combined first mold and the second mold to obtain the water-soluble polymer spheres. When the above steps are performed, the following advantages are obtained: the shrinkage rate of the solution is adjusted during freeze drying, thereby preparing a spherical freeze-dried product, the prepared freeze-dried product is easy to fall off from the mold, so that the recovery rate is maximized, and the freeze-drying efficiency is excellent, and the pore size and distribution of the prepared freeze-dried product are constant and the strength is high.

[0064] As an example, the water-soluble polymer may be a natural water-soluble polymer. As another example, the water-soluble polymer may be a biosynthesized natural polymer, preferably, hyaluronic acid or a salt thereof.

[0065] As an example, the water-soluble polymer solution may be a water-soluble polymer aqueous solution.

[0066] Preferably, the water-soluble polymer solution may be a hyaluronic acid-based composition solution comprising a hyaluronic acid-based compound and a hydrophilic polymer.

[0067] As an example, the recovery rate in the preparation method of the water-soluble polymer spheres is 90% or more, preferably 91% or more, more preferably 93% or more, and further preferably 95% or more. Within this range, the method has the advantage of excellent economy.

[0068] In the present invention, "hyaluronic acid-based compounds" refer to hyaluronic acid, hyaluronates and their derivatives, and "hyaluronic acid or hyaluronates" simply lists the types, rather than excluding any one component, and also includes the meaning of "a mixture of hyaluronic acid and hyaluronates".

[0069] As a preferred embodiment, the hyaluronic acid-based composition solution comprises: 100 parts by weight of a matrix polymer consisting of A) 44 to 93% by weight of hyaluronic acid or hyaluronate with an average molecular weight of less than 100,000 Dalton, B-1) 0.5 to 12% by weight of hyaluronic acid or hyaluronate with an average molecular weight of 100,000 to 1,000,000 Dalton, B-2) 0.1 to 5% by weight of hyaluronic acid or hyaluronate with an average molecular weight greater than 1,000,000 Dalton, and C) 1 to 50% by weight of a hydrophilic polymer; and 0 to 25 parts by weight of an effective ingredient, wherein the hyaluronic acid salt is selected from sodium hyaluronate, hyaluronic acid The hydrophilic polymer is selected from maltodextrin, dextrin, guar gum, xanthan gum, gum arabic, carboxymethyl cellulose, agar, β-glucan, pullulan, collagen, alginate, cross-linked hyaluronate, cross-linked hyaluronic acid, chitosan, heparin, gelatin, elastin, hydrolyzed elastin, fibrin, laminin, fibronectin, proteoglycan, heparan sulfate, chondroitin sulfate, dermatan sulfate and keratan sulfate. The active ingredient may include one or more selected from cetearyl olive oil ester (Cetearyl Olivate), Ethylhexyl Olivate, Hydroxypropyltrimonium Chloride Hyaluronic Acid, Sodium Hexanoyl Hyaluronate, Sodium Oleyl Hyaluronate, Sodium Acetylated Hyaluronate, Arbutin, Broussonetia papyrifera Extract, Licorice Extract, Caper Seed Extract, Atractylodes macrocephala Extract, Ascorbic Acid Ethyl Ether, Ascorbyl Glucoside, Niacinamide, Magnesium Ascorbyl Phosphate, Ascorbic Acid and Its Derivatives, Kojic Acid, Glutathione, Tyrosinase, Dioscorea chinensis, Macelignan, Vitamins and Their Derivatives, Centella asiatica, Ubidecarenone, Peony Extract, Polyethoxylated Retinamide, Hydroxyproline, Retinoic Acid and Its Derivatives, α-Hydroxy Acid (AHA), Adenosine, Botulinum Toxin and Its Derivatives; Rosemary , cloves, cypress seeds, turmeric, green tea, black bean seed coat, rose petals, peony roots, platycodon, bean sprouts, colored barley seed coat, camellia petals, buckwheat, grapefruit, licorice, coptis, astragalus, phellodendron, scutellaria, cinnamon, forage, raspberry, gallnut, juniper, forsythia, pepper leaves, mint, snakeberry, mulberry, saururus, pine, wormwood, houttuynia, somei yoshino cherry, northern scutellaria or laurel bamboo stem extract. Within this range, it has the following advantages, which is beneficial to the freeze-drying mold of the present invention, and even if a low molecular weight hyaluronic acid-based compound that has been difficult to ensure mechanical strength in the past is used, the mechanical strength is excellent, and further due to the low molecular weight, the dissolution time is short and the stickiness is less, thereby providing a dry hyaluronic acid-based composition with excellent feel in use.

[0070] Furthermore, preferably, the hyaluronic acid-based composition solution may comprise: 100 parts by weight of a matrix polymer consisting of A) 45 to 65% by weight of hyaluronic acid or hyaluronate having an average molecular weight of less than 100,000 Dalton, B-1) 1 to 15% by weight of hyaluronic acid or hyaluronate having an average molecular weight of 100,000 to 1,000,000 Dalton, B-2) 0.5 to 2% by weight of hyaluronic acid or hyaluronate having an average molecular weight greater than 1,000,000 Dalton, and C) 20 to 50% by weight of a hydrophilic polymer; and 0.1 to 25 parts by weight of an effective ingredient. Within this range, the composition has the following advantages: it is suitable for the freeze-drying mold of the present invention, has excellent mechanical strength, and has a short dissolution time and less stickiness due to its low molecular weight, thus having an excellent feel during use.

[0071] Preferably, the hyaluronate may be sodium hyaluronate, in which case it is effective for skin beauty and wound treatment.

[0072] In the present invention, Dalton can be defined as a neutral 12 1 / 12 of the atomic mass of C.

[0073] In the present invention, the average molecular weight is calculated by multiplying the molecular weight of each peak of hyaluronic acid and / or hyaluronate obtained by GPC measurement by the peak area, accumulating the calculated values ​​for each peak, and dividing the accumulated value by the total peak area to calculate the average molecular weight.

[0074] As an example, in the above-mentioned water-soluble polymer solution, the water content can be 10 times to 1000 times, preferably 20 times to 500 times, more preferably 30 times to 200 times, further preferably 40 times to 100 times, and further preferably 40 times to 80 times, based on the total weight of the water-soluble polymer. Within this range, the freeze-drying yield is improved.

[0075] As an example, in the above-mentioned hyaluronic acid-based composition solution, based on the total weight of the above-mentioned A) hyaluronic acid or hyaluronate, the water content can be 10 times to 1000 times, preferably 20 times to 500 times, more preferably 30 times to 200 times, further preferably 40 times to 100 times, and further preferably 40 times to 80 times. Within this range, the freeze-drying yield is improved.

[0076] As an example, the water can be replaced by an organic solvent in a range of less than 20 weight %, preferably, in a range of less than 10 weight %, more preferably, in a range of less than 5 weight %, relative to the total weight of water. As a specific example, the water can be replaced in a range of more than 1 weight % to less than 20 weight %, preferably, in a range of 1 to 10 weight %, more preferably, in a range of 1 to 5 weight %. Within this range, the desired shape can be well prepared, the drying efficiency is excellent, and the freeze-drying yield is high.

[0077] Preferably, the organic solvent is one or more selected from alcohols, and more preferably may be ethanol.

[0078] As an example, the diameter of the water-soluble polymer spheres can be 3 to 25 mm, preferably 5 to 20 mm, more preferably 8 to 15 mm, and further preferably 10 to 12 mm. Within this range, the water-soluble polymer spheres have the advantages of being easy to handle or having a large utilization rate as cosmetic materials, etc.

[0079] As an example, the compressive strength (average, N) of the water-soluble polymer spheres can be greater than 1, preferably greater than 2, and more preferably greater than 2.2. As a specific example, it can be from 1 to 5, preferably from 1.5 to 4, and more preferably from 2 to 3. Within this range, the water-soluble polymer spheres have the advantages of easy handling or great utilization as cosmetic materials, etc.

[0080] As an example, the dissolution time (seconds) of the water-soluble polymer spheres may be less than 20 seconds, preferably less than 19 seconds, more preferably less than 18 seconds, and further preferably less than 18 seconds. Within this range, the water-soluble polymer spheres have the advantages of being easy to handle or having a high utilization rate as cosmetic materials, etc.

[0081] Preferably, the freezing step may include: a first freezing step, freezing the water-soluble polymer solution at -1 to -10°C for 10 to 60 minutes at normal pressure; a second freezing step, cooling the first frozen water-soluble polymer solution at normal pressure for 1 to 10 hours, until -40 to -60°C; and a third freezing step, keeping the second frozen water-soluble polymer solution at -40 to -60°C for 30 to 5 hours at normal pressure. Within this range, the advantages are high freezing efficiency, excellent mechanical strength of the dried water-soluble polymer, short dissolution time, less stickiness, and thus excellent feel in use.

[0082] In the present invention, normal pressure refers to the pressure when the pressure is not intentionally reduced or increased, and generally refers to a pressure of about 1 atmosphere like atmospheric pressure. As a specific example, it refers to a pressure in the range of 1 bar ± 300 Pa.

[0083] As a preferred embodiment, the above-mentioned freezing step may include: a first freezing step, freezing the above-mentioned water-soluble polymer solution at -3 to -8°C for 20 to 40 minutes at normal pressure; a second freezing step, cooling the first frozen water-soluble polymer solution at normal pressure for 5 to 9 hours, until -40 to -50°C; and a third freezing step, keeping the second frozen water-soluble polymer solution at -40 to -50°C for 1 to 3 hours at normal pressure. Within this range, it has the following advantages: high freezing efficiency, excellent mechanical strength of the prepared dry water-soluble polymer, short dissolution time, less sticky feeling, and therefore excellent feel in use.

[0084] Preferably, the above-mentioned drying step may include: a first drying step, heating the frozen water-soluble polymer solution in stages or continuously for 5 to 30 hours at 10 to 40°C at 100 to 1000 μbar; and a second drying step, drying the first dried water-soluble polymer solution at 20 to 50°C at 1 to 99 μbar for 1 to 20 hours. Within this range, it has the following advantages: high drying efficiency, excellent mechanical strength of the dried water-soluble polymer, short dissolution time, less stickiness, and thus excellent feel in use.

[0085] As a preferred embodiment, the above-mentioned drying step may include: a step of keeping the frozen water-soluble polymer solution at less than -40°C to below -10°C for 2 to 6 hours at 100 to 1000 microbars; a step of keeping it at greater than -10°C to below -5°C for 2 to 6 hours; a step of keeping it at greater than -5°C to below 0°C for 2 to 6 hours; a step of keeping it at greater than 0°C to below 10°C for 30 minutes to 2 hours; a step of keeping it at greater than 10°C to below 20°C for 30 minutes to 2 hours; a step of keeping it at greater than 20°C to below 30°C for 30 minutes to 2 hours; and a step of keeping it at greater than 30°C to below 45°C for 30 minutes to 2 hours. Within this range, it has the following advantages: high drying efficiency, excellent mechanical strength of the dried water-soluble polymer solution, short dissolution time, less sticky feeling, and thus excellent feel in use.

[0086] The method for preparing the water-soluble polymer solution may include the steps of heating and stirring for dispersion before freezing as required.

[0087] As an example, the heating and stirring may be performed at 5 to 50°C, and preferably, may be performed at 10 to 25°C.

[0088] Furthermore, the method for preparing the water-soluble polymer solution may selectively include the steps of filtering, sterilizing, or both filtering and sterilizing after the dispersing step.

[0089] As an example, the above filtration step can be implemented using a micro filter with a pore diameter of 0.1 to 5 μm, preferably, it can be implemented using a micro filter with a pore diameter of 0.3 to 1 μm, and more preferably, it can be implemented using a micro filter with a pore diameter of 0.5 to 0.8 μm.

[0090] In the present invention, the diameter of the pores may be based on the definition generally recognized in the technical field of microfilters, and may have the specifications described in commercially available microfilter products.

[0091] As an example, the above-mentioned filtration and sterilization steps can be carried out at 20 to 25°C and a maximum of 5 bar, respectively. Preferably, they can be carried out at 20 to 25°C and 1.5 to 3 bar, and more preferably, they can be carried out at 20 to 25°C and 2 to 3 bar.

[0092] The device used in the freeze-drying of the present invention is a device that is generally usable in the technical field to which the present invention belongs, and is not particularly limited when it can achieve the temperature and pressure conditions of the present invention. As an example, it can be a separate freeze-drying device in which a freezer (freezer) and a vacuum dryer are separated, or an integrated freeze-drying device in which a freezing device, a vacuum device and a heater are combined.

[0093] Hereinafter, preferred embodiments of the freeze-drying mold of the present invention will be described in detail with reference to the accompanying drawings, but this is merely an example of the present invention and does not limit the technical scope of the present invention.

[0094] the following Figure 1 In the perspective view showing the bottom surface of the first mold 100 of the present invention, the insertion portion 130 is formed in a stepped manner, and a plurality of hemispherical first receiving grooves 110 are formed in a grid arrangement on the insertion portion 130. In addition, when the first mold 100 and the second mold 200 are inserted and combined to form a freeze-drying mold, in order to fix them, a first fastening hole 140 is formed in the center of the first mold 100, and second fastening holes 141 are formed at the edges of the four directions outside the insertion portion 130. The above-mentioned fastening holes can be fixed by fastening components such as bolts, nuts, fixing pins, etc.

[0095] Although not specifically shown in the figure, the length of the first mold 100 is 300 mm in the range of about 280 to 320 mm, the width is 150 mm in the range of about 130 to 170 mm, the height is 16 mm in the range of about 12 to 18 mm, and the radius of the first receiving groove 110, that is, the depth of the groove is 8 mm in the range of about 6 to 10 mm. Within this range, the freeze-drying process is easy to implement, the freeze-drying efficiency is excellent, and the freeze-dried product is easy to handle.

[0096] Furthermore, the material of the first mold 100 is formed of a polyacetal resin (POM resin) with low thermal conductivity. Even if a separate coating treatment is not performed on the bottom surface, the shrinkage rate of the solution during freeze-drying can be easily adjusted, thereby easily preparing spherical freeze-dried products, and has the following advantages: the prepared freeze-dried products can easily fall off the mold, maximizing the recovery rate of the raw materials, and the prepared pore size and distribution are constant, the strength is high, and no film is formed on the surface.

[0097] the following Figure 2 The top view of the upper surface of the first mold 100 of the present invention is shown. Figure 1 The first mold 100 shown is turned over to form the entrances of a plurality of discharge portions 120 connected to the first receiving groove 110. When the first mold 100 is combined on the second mold 200 filled with the water-soluble polymer solution, the water-soluble polymer solution exceeding the capacity of the receiving portion 11 can be discharged through the above-mentioned discharge portions 120, and when freeze-drying, if the water-soluble polymer solution expands or shrinks, the excess or insufficient water-soluble polymer solution can enter and exit through the above-mentioned discharge portions 120, and the vaporized water can also be discharged through the above-mentioned discharge portions 120. As another example, after combining the first mold 100 and the second mold 200, the solution to be freeze-dried, such as the water-soluble polymer solution, can be put into each receiving portion 11 formed by combining the first receiving groove and the second receiving groove through the above-mentioned discharge portions 120.

[0098] the following Figure 3 In order to show the top view of the bottom surface of the first mold 100 of the present invention, the insertion part 130 is formed in a stepped manner, and a plurality of hemispherical first receiving grooves 110 are formed in a grid arrangement on the insertion part 130, and the discharge part 120 is connected to the bottom surface of the first receiving groove 110. In addition, in order to fix the freeze-drying mold 10, a first fastening hole 140 is formed in the center of the first mold 100, and second fastening holes 141 are formed at the edges of the four directions outside the insertion part 130.

[0099] the following Figure 4 This is a side view showing the side surface of the first mold 100 of the present invention. The insertion portion 130 forming the first receiving groove 110 is protruded in a stepped manner.

[0100] the following Figure 5 The sectional view is a cross-sectional view of the first mold 100 of the present invention, wherein a hemispherical first receiving groove 110, a discharge portion 120 for discharging excess freeze-dried solution, and a first fastening hole 140 for fixing the freeze-drying mold 10 are formed inside the first mold 100.

[0101] the following Figure 6The third embodiment is a three-dimensional diagram showing the upper surface of the second mold 200 of the present invention. An insertion groove 230 is formed by being recessed corresponding to the first mold 100, and a plurality of hemispherical second receiving grooves 210 are formed on the insertion groove 230 in a grid arrangement. The second receiving groove 210 is combined with the first receiving groove 110 of the first mold to form a sphere. Furthermore, when the freeze-drying mold 10 is formed by combining the first mold 100 and the second mold 200, in order to fix it, a first fastening hole 140' is formed in the center of the second mold 200, and second fastening holes 141' are formed at the edges of the four directions outside the insertion groove 230. The fastening holes of the first mold 100 and the second mold 200 can be fixed to each other by fastening components such as bolts, nuts, fixing pins, etc., so that the water-soluble polymer solution filled in the receiving portion 11 will not leak to the outside during the freeze-drying process, but will be stably filled in the receiving portion.

[0102] Although not specifically shown in the figure, the length of the second mold 200 is 300 mm in the range of about 280 to 320 mm, the width is 150 mm in the range of about 130 to 170 mm, the height is 16 mm in the range of about 12 to 18 mm, the radius of the second receiving groove 210, that is, the depth of the groove is 8 mm in the range of about 6 to 10 mm, and the depth (a) of the insertion groove 230 is 8 mm in the range above the depth of the above-mentioned first receiving groove. Within this range, it has the following advantages: the freeze-drying process is easy to implement, the freeze-drying efficiency is excellent, the freeze-dried product is easy to handle, and the freeze-dried product of the desired shape is obtained.

[0103] Furthermore, the material of the second mold 200 is formed of aluminum metal with high thermal conductivity, the entire second mold is subjected to white hard anodizing treatment, and polytetrafluoroethylene is coated on the upper surface. Thus, the shrinkage rate of the solution during freeze drying is easily adjusted, thereby preparing a spherical freeze-dried product, and has the following advantages: the prepared freeze-dried product is easy to fall off from the mold, so that the raw material recovery rate is maximized, and the prepared freeze-dried product has a constant pore size and distribution, high strength, and no film is formed on the surface.

[0104] the following Figure 7 To show a top view of the upper surface of the second mold 200 of the present invention, the insertion groove 230 is recessed in a step-forming manner, and a plurality of hemispherical second receiving grooves 210 are formed in a grid arrangement on the insertion groove 230, and in order to fix the freeze-drying mold 10, a first fastening hole 140' is formed in the center of the second mold 200, and second fastening holes 141' are formed at the edges in four directions outside the insertion groove 230.

[0105] the following Figure 8 This is a side view showing the side of the second mold 200 of the present invention. The insertion groove 230 forming the second receiving groove 210 is recessed in the inside to form a step, and therefore cannot be seen from the side.

[0106] the following Fig. 9 This is a cross-sectional view showing a cross section of the second mold 200 of the present invention. A hemispherical second receiving groove 210 and a second fastening hole 141 ′ for fixing the freeze-drying mold 10 are formed inside the second mold 200 .

[0107] the following Fig.10 The present invention is a sectional view showing the cross section of a freeze-drying mold 10 formed by combining a first mold 100 and a second mold 200 of the present invention, wherein a discharge portion 120 and a receiving portion are formed, wherein the discharge portion 120 discharges excess water-soluble polymer solution in the receiving portion 11 or water vaporized during freeze-drying and is discharged, and wherein the receiving portion is formed into a spherical shape by combining a first receiving groove and a second receiving groove, wherein a freeze-drying target solution enters the receiving portion, and the fastening holes of the first mold 100 and the second mold 200 are combined to pass through the freeze-drying mold.

[0108] In order to help understand the present invention, preferred embodiments are proposed below. However, the following embodiments are only used to illustrate the present invention. Various changes and modifications can be made within the scope of the present invention and the technical concept. This is obvious to ordinary technicians in the technical field to which the present invention belongs. Such deformation and modification also belong to the claims.

[0109] [Example]

[0110] Preparation Example

[0111] 100 parts by weight of hyaluronic acid with an average molecular weight of 10,000 Daltons as a low molecule of HA, 6.5 parts by weight of sodium hyaluronate with an average molecular weight of 220,000 Daltons as a medium molecule of HA, 1.5 parts by weight of sodium hyaluronate with an average molecular weight of 1,400,000 Daltons as a high molecule of HA, and 27 parts by weight of a mixture of alginate and hydrolyzed collagen as a hydrophilic polymer (weight ratio 1:3) were weighed, and slowly added to 1L of pure water in the reactor, and stirred until completely dissolved, thereby preparing a hyaluronic acid-based composition solution. At this time, stirring was performed at about 10 to 15°C, and attention was paid to not generating stirring heat during stirring. Stirring for about 1 hour or more, confirming the dissolved state, and collecting the dissolved solution at the upper, middle and lower positions of the reactor, respectively, and measuring the drying loss to confirm complete dissolution (the drying loss at the upper, middle and lower positions was the same).

[0112] Example 1, Comparative Examples 1 to 7 and Reference Example 1

[0113] The prepared hyaluronic acid-based composition solution was poured into the second mold (corresponding to the following Figure 6The discharge amount is about 250 to 350 mL, and the discharge amount of the dispensing device is adjusted according to the situation. Figure 1 The insertion portion of the upper plate of the second mold (corresponding to the following table 1) is inserted into the second mold (corresponding to the following table 1) Figure 6 ) of the lower plate, as shown below Fig.10 The first mold and the second mold are combined as shown, and the first mold and the second mold are completely close to each other using screws suitable for the fastening holes. The freeze-drying mold injected with the hyaluronic acid-based composition solution as described above is inserted into a freeze dryer, and freeze-dried according to the freeze-drying conditions described in Table 2 below. However, step 10 in the freeze-drying conditions described in Table 2 below is omitted in Reference Example 1. After freeze drying is completed, the above mold is recovered from the freeze dryer to obtain a spherical freeze-dried hyaluronic acid-based composition.

[0114] [Table 1]

[0115]

[0116]

[0117] (The above-mentioned POM is polyacetal, and the above-mentioned PE is polyethylene.)

[0118] [Table 2]

[0119]

[0120] [Test example]

[0121] The properties of the hyaluronic acid-based composition spheres obtained in Example 1, Comparative Examples 1 to 7 and Reference Example 1 were measured by the following method, and the results are shown in Tables 3 and 4 below. Figures 11 to 13 middle.

[0122] *Appearance characteristics: Observed with naked eyes and photographed (see below Fig.11 ) to confirm the surface characteristics. At this time, the situation that the separation was complete spherical, the surface was smooth, there was no undried part, the strength was high, and no film was formed on the surface was evaluated as good.

[0123] *Recovery rate: After confirming the appearance, size and weight of the freeze-dried product, the product that meets the conditions of 10-11 mm in diameter and 20 mg in weight is selected for recovery. The recovery rate is calculated by confirming the ratio of the number of recovered freeze-dried products to the total number of receiving grooves in the mold.

[0124] *Compression strength (N): The compression strength was measured using a mechanical testing system (manufacturer: Instron, model name: 3340 series). In detail, the freeze-dried spherical hyaluronic acid-based composition was installed in a compression strength fixture and compressed to 50% of the height of the product at a compression speed of 2 mm / min to measure the maximum compression strength (N).

[0125] *Dissolution time (dissolving ability): After a container capable of immersing the hyaluronic acid-based composition is sufficiently filled with water, the hyaluronic acid-based composition is dropped onto the water and the time required for complete dissolution is measured for evaluation.

[0126] [Table 3]

[0127]

[0128] As shown in Table 3 above, it can be confirmed that when the freeze-drying mold of the present invention is used to prepare hyaluronic acid-based composition spheres (Example 1), its appearance characteristics, recovery rate, strength and dissolution time are significantly superior to those of Comparative Examples 1 to 7 which are not the case.

[0129] However, even when the freeze-drying mold of the present invention is used to significantly shorten the freeze-drying time, especially when the drying time is significantly shortened (reference example 1), as a common sense result, it can be confirmed that some undried hyaluronic acid-based composition spheres are obtained, thereby reducing the recovery rate, etc.

[0130] And, as follows Fig.11 As shown, it can be confirmed that the surface of the hyaluronic acid-based composition sphere prepared in Example 1 is clean and has a complete spherical shape, but all of Comparative Examples 1 to 7 do not have a complete spherical shape and are difficult to separate from the mold.

[0131] And, as follows Fig.12 and Fig.13 As shown, it can be confirmed that in the case of the freeze-drying mold remaining after the hyaluronic acid-based composition spheres are recovered after freeze-drying in Example 1, the receiving portion is clean without any residual residue, but a large amount of hyaluronic acid-based composition remains as residue in the receiving portion of the freeze-drying mold remaining after the hyaluronic acid-based composition spheres are recovered in Comparative Examples 1 to 7.

[0132] Description of Reference Numerals

[0133] 10: Freeze drying mold 100: First mold

[0134] 110: first receiving groove 120: discharge portion

[0135] 130: Insertion portion 140: First fastening hole of the first mold

[0136] 141: second fastening hole of the first mold 200: second mold

[0137] 210: second receiving slot 230: insertion slot

[0138] 140': first fastening hole of the second mold 141': second fastening hole of the second mold

[0139] 11: Containment

Claims

1. A mold for freeze-drying a spherical water-soluble polymer, characterized in that: include: A first mold, having a plurality of first hemispherical receiving grooves continuously formed on the bottom surface, the first hemispherical receiving grooves being used to receive a water-soluble polymer solution containing a solvent in an amount of 10 to 1000 times the total weight of the water-soluble polymer, and having a discharge portion formed on the upper surface, the discharge portion being used to communicate with the first hemispherical receiving grooves respectively and discharge excess water-soluble polymer solution, expanded water-soluble polymer freeze-dried product or water generated during freeze-drying; as well as The second mold has a plurality of second hemispherical receiving grooves formed on the upper surface, and is combined with the first mold facing each other so that the first hemispherical receiving grooves and the second hemispherical receiving grooves form a receiving portion, and the second mold is made of a material with a thermal conductivity of 225 to 250 W / mK based on 1 atmospheric pressure and 20° C., The first mold is formed of a material having a thermal conductivity of 200 to 250 W / mK lower than that of the second mold at 1 atmosphere and 20°C. The first mold is formed by including one or more selected from polyacetal resin and polyolefin resin, and the second mold is formed by including one or more metals selected from aluminum, duralumin, tungsten, iron, cast iron, carbon steel, stainless steel, copper, bronze, brass, lead, nickel, gold and silver.

2. The mold for freeze-drying of spherical water-soluble polymers according to claim 1, characterized in that: The receiving portion is spherical.

3. The mold for freeze-drying of spherical water-soluble polymers according to claim 2, characterized in that: The diameter of the receiving portion is 10 to 15 mm.

4. The mold for freeze-drying of spherical water-soluble polymers according to claim 1, characterized in that: An insertion portion is formed on the bottom surface of the first mold in a stepped manner, and the first hemispherical receiving groove is formed on the surface of the insertion portion. A recessed insertion groove is formed on the upper surface of the second mold so that the insertion part can be inserted and combined, and the second hemispherical receiving groove is formed on the inner surface of the insertion groove. After the water-soluble polymer is filled into the insertion groove, the remaining water-soluble polymer is discharged through the discharge portion.

5. The mold for freeze-drying of spherical water-soluble polymers according to claim 1, characterized in that: More than one matching fastening hole is formed in the first mold and the second mold so that they can be fastened by a fastening component.

6. The mold for freeze-drying of spherical water-soluble polymers according to claim 1, characterized in that: The surface of the second mold is anodized.

7. The mold for freeze-drying a spherical water-soluble polymer according to claim 6, characterized in that: The anodized surface is sealed, colored, or both sealed and colored.

8. The mold for freeze-drying of spherical water-soluble polymers according to claim 6, characterized in that: The material constituting the first mold is applied to the upper surface of the second mold.

9. A method for preparing water-soluble polymer spheres, characterized in that: include: The step of combining the first mold and the second mold, wherein a plurality of first hemispherical receiving grooves are continuously formed on the bottom surface of the first mold, and a discharge portion is formed on the upper surface so as to be respectively connected with the first hemispherical receiving grooves, and a plurality of second hemispherical receiving grooves are formed on the upper surface of the second mold, and the second hemispherical receiving grooves are combined with the first mold facing each other so that the first hemispherical receiving grooves and the second hemispherical receiving grooves form a receiving portion, and the second mold is made of a material with a thermal conductivity of 225 to 250 W / mK based on 1 atmospheric pressure and 20° C., and the thermal conductivity of the material forming the first mold based on 1 atmospheric pressure and 20° C. is 200 to 250 W / mK lower than that of the second mold; A freeze drying step, the freeze drying step comprising a freezing step and a drying step, in which a water-soluble polymer solution containing a solvent in an amount of 10 to 1000 times the total weight of the water-soluble polymer is supplied to the second mold before the first mold is combined with the second mold or supplied to the receiving part through the discharge part after the combination, and is frozen at a temperature below -1°C, and in the drying step, the frozen water-soluble polymer solution is heated and dried under reduced pressure; as well as The step of separating the combined first mold and the second mold to obtain water-soluble polymer balls that do not form a film on the surface, wherein the first mold is formed by comprising one or more selected from polyacetal resin and polyolefin resin, and the second mold is formed by comprising one or more metal selected from aluminum, duralumin, tungsten, iron, cast iron, carbon steel, stainless steel, copper, bronze, brass, lead, nickel, gold and silver, The drying step comprises: The step of sequentially maintaining the frozen water-soluble polymer solution at a temperature of less than -40°C to below -10°C for 2 to 6 hours at 100 to 1000 microbars; A step of maintaining the temperature at a temperature greater than -10°C to below -5°C for 2 hours to 6 hours; A step of maintaining the temperature at a temperature between greater than -5°C and below 0°C for 2 hours to 6 hours; A step of maintaining the temperature at a temperature between greater than 0°C and below 10°C for 30 minutes to 2 hours; A step of maintaining the temperature at a temperature between 10°C and 20°C for 30 minutes to 2 hours; A step of maintaining the temperature at a temperature between 20°C and 30°C for 30 minutes to 2 hours; and A step of maintaining the temperature at a temperature between 30°C and 45°C for 30 minutes to 2 hours.

10. The method for preparing water-soluble polymer spheres according to claim 9, characterized in that: The water-soluble polymer solution is a hyaluronic acid-based composition solution.

11. The method for preparing water-soluble polymer spheres according to claim 10, characterized in that: The hyaluronic acid-based composition solution comprises: 100 parts by weight of a matrix polymer consisting of A) 44 to 93% by weight of hyaluronic acid or hyaluronate with an average molecular weight of less than 100,000 Daltons, B-1) 0.5 to 12% by weight of hyaluronic acid or hyaluronate with an average molecular weight of 100,000 to 1,000,000 Daltons, B-2) 0.1 to 5% by weight of hyaluronic acid or hyaluronate with an average molecular weight greater than 1,000,000 Daltons, and C) 1 to 50% by weight of a hydrophilic polymer; and less than 25 parts by weight of an active ingredient, The hyaluronate is one or more selected from sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, cobalt hyaluronate and tetrabutylammonium hyaluronate. The hydrophilic polymer is one or more selected from maltodextrin, dextrin, guar gum, xanthan gum, gum arabic, carboxymethyl cellulose, agar, β-glucan, pullulan, collagen, alginate, cross-linked hyaluronate, cross-linked hyaluronic acid, chitosan, heparin, gelatin, elastin, hydrolyzed elastin, fibrin, laminin, fibronectin, proteoglycan, heparan sulfate, chondroitin sulfate, dermatan sulfate and keratan sulfate, The active ingredient is selected from the group consisting of cetearyl olive oil ester, ethylhexyl olive oil ester, hydroxypropyltrimethylammonium chloride hyaluronic acid, sodium caproyl hyaluronate, sodium oleoyl hyaluronate, sodium acetylated hyaluronate, arbutin, paper mulberry extract, licorice extract, smilax china seed extract, atractylodes macrocephala extract, ascorbic acid ethyl ether, ascorbyl glucoside, niacinamide, magnesium ascorbyl phosphate, ascorbic acid and its derivatives, kojic acid, glutathione, tyrosinase, dioscorea lignan, mace lignan, vitamins and their derivatives, centella asiatica, ubidecarenone, peony extract, polyethylene glycol Oxylated retinamide, hydroxyproline, retinoic acid and its derivatives, alpha-hydroxy acid (AHA), adenosine, botulinum toxin and its derivatives; one or more of extracts of rosemary, clove, cypress seed, turmeric, green tea, black bean seed coat, rose petals, peony root, platycodon, bean sprouts, colored barley seed coat, camellia petals, buckwheat, grapefruit, licorice, coptis root, astragalus, phellodendron, scutellaria, cinnamon, forage grass, raspberry, gallnut, juniper, forsythia, pepper leaf, mint, snakeberry, mulberry, saururus chinensis, pine, wormwood, houttuynia cordata, Somei Yoshino cherry, northern Chinese bamboo or bamboo stem.

12. The method for preparing water-soluble polymer spheres according to claim 9, characterized in that: The freezing step comprises: The first freezing step is to freeze the water-soluble polymer solution at -3 to -8°C under normal pressure for 20 to 40 minutes; A second freezing step, cooling the first frozen water-soluble polymer solution to -40 to -50°C at normal pressure for 5 to 9 hours; and In the third freezing step, the second frozen water-soluble polymer solution is kept at -40 to -50°C under normal pressure for 1 to 3 hours.

13. A water-soluble polymer ball, characterized in that: The water-soluble polymer sphere is prepared by the preparation method according to any one of claims 9 to 12, has an average compression strength of 2N or more, a diameter of 10 to 15 mm, and does not form a film on the surface.

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