KR102215559B1 - Preparing method of dry hyaluronic acid based composition and dry hyaluronic acid based composition - Google Patents

Abstract

The present invention relates to a method for preparing a dry hyaluronic acid-based composition and a dry hyaluronic acid-based composition and, more particularly, to a method for preparing a dry hyaluronic acid-based composition and a dry hyaluronic acid-based composition, in which the composition comprises: A) 44 to 93 wt% of hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons; B) 0.6 to 17 wt% of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 100,000 Daltons or more; and C) 1 to 50 wt% of hydrophilic polymer, and the method comprises the steps of: freezing the hyaluronic acid-based composition at -1°C or less under atmospheric pressure; and heating and drying the resulting frozen hyaluronic acid-based composition under reduced pressure (evacuation). According to the present invention, there is an effect of providing a method for preparing a dry hyaluronic acid-based composition and a dry hyaluronic acid-based composition prepared thereby, in which the composition has no toxicity, but shows excellent product stability, excellent mechanical strength, short dissolution time, low stickiness, excellent feeling of use, and well expression of the original performance of the active ingredient.

Description

Manufacturing method of dry hyaluronic acid-based composition and dry hyaluronic acid-based composition TECHNICAL FIELD {PREPARING METHOD OF DRY HYALURONIC ACID BASED COMPOSITION AND DRY HYALURONIC ACID BASED COMPOSITION}

The present invention relates to a method for preparing a dry hyaluronic acid-based composition and a dry hyaluronic acid-based composition, and more particularly, it is non-toxic, excellent product stability, excellent mechanical strength, short dissolution time, and low stickiness, resulting in excellent feeling of use. , The present invention relates to a method for preparing a dry hyaluronic acid-based composition and a dry hyaluronic acid-based composition that exhibits the original performance of the active ingredient well.

Hyaluronic acid is a type of polysaccharide in which repeating units consisting of N-acetyl-glucosamine and D-glucuronic acid are linearly connected. It is a biopolymer material, and was first isolated from the liquid filling the eyeballs of animals [Meyer K. et al. al., Journal of Biology and Chemistry 107 629-34 (1934)] Since then, it has been known to exist in many places in the placenta of animals, synovial fluid, pleural fluid, skin, and roosters. It is also produced in Streptococcus genus microorganisms such as Streptococcus equi and Streptococcus zooepidemecus.

Hyaluronic acid has excellent biocompatibility and high viscoelasticity in solution, and is widely used not only for cosmetic applications such as cosmetic additives, but also for various pharmaceutical applications such as ophthalmic surgical aids, joint function improving agents, drug delivery substances and eye drops. However, hyaluronic acid itself is easily decomposed in vivo or under conditions such as acid and alkali, and its use is limited. Therefore, many studies have been conducted to develop structurally stable hyaluronic acid derivatives through cross-linking or attaching functional groups to hyaluronic acid (Laurent, TC, et al., Portland Press Ltd, London, 1998). ).

In addition, as an attempt to apply to various uses by modifying the physicochemical and biological properties of hyaluronic acid, it is used as a carrier for a support or drug delivery system for the purpose of culturing and transplanting cells or tissues, wound covering materials, dental materials, and medical materials. It is known to prepare hyaluronic acid in the form of a sponge.

Looking at the manufacturing method of hyaluronic acid sponge, natural hyaluronic acid is easily soluble in water and it is difficult to obtain a sponge shape of good properties.Therefore, it is known to crosslink hyaluronic acid so that the sponge shape can be maintained after drying by changing hyaluronic acid to insoluble. have. To prepare such a hyaluronic acid crosslinked product, various crosslinking agents are used, and representative of them are divinyl sulfone (US Patent No. 4582865), formaldehyde (Japanese Patent Publication No. 60-130601), and carbodiimide (International Publication No. Patent No. 94/2517), an epoxide (US Patent No. 2011-0268706), and the like, have been proposed.

However, in the case of using divinyl sulfone or aldehydes as a crosslinking agent, the use is limited because cytotoxicity due to unreacted residues may be a problem, and water-soluble carbodies used for crosslinking biomaterials containing amino acids. Imides do not show toxicity in the body, but have a disadvantage that they exhibit crosslinking effects when used in excess and are expensive.

Korean Patent No. 2010-0079363

In order to solve the problems of the prior art as described above, the present invention is non-toxic, excellent product stability, excellent mechanical strength, short dissolution time and low stickiness, excellent feeling of use, and drying in which the original performance of the active ingredient is well expressed. It is an object of the present invention to provide a method for preparing a hyaluronic acid composition and a dry hyaluronic acid composition.

All of the above and other objects of the present invention can be achieved by the present description described below.

In order to achieve the above object, the present invention provides A) hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons (Dalton), 44 to 93% by weight, B) hyaluronic acid or hyaluronic acid salt having an average molecular weight of 100,000 Daltons or more A freezing step of freezing the hyaluronic acid-based composition containing 0.6 to 17% by weight and C) 1 to 50% by weight of a hydrophilic polymer at -1°C or less under normal pressure, and heating and drying the frozen hyaluronic acid-based composition under reduced pressure (Evacuation) It provides a method for producing a dry hyaluronic acid-based composition comprising a drying step.

In addition, the present invention provides a dry hyaluronic acid-based composition prepared by the method for preparing the dry hyaluronic acid-based composition.

In addition, the present invention A) hyaluronic acid or hyaluronic acid salt of an average molecular weight of less than 100,000 Daltons (Dalton) 44 to 93% by weight, B-1) an average molecular weight of 100,000 to 1,000,000 Daltons (Dalton) of hyaluronic acid or hyaluronic acid 0.5 to 12% by weight; B-2) 0.1 to 5% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,000,000 Daltons, and C) 100 parts by weight of a base polymer consisting of 1 to 50% by weight of a hydrophilic polymer; And 0 to 25 parts by weight of an active ingredient, wherein the hyaluronic acid salt is selected from the group consisting of sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, cobalt hyaluronate, and tetrabutyl ammonium hyaluronate. At least one type, and the hydrophilic polymer is maltodextrin, dextrin, guar gum, xantam gum, gum arabic, carboxymethylcellulose, agar, gum arabic, beta glucan and fluran, collagen, algin, cross-linked hyaluronic acid, cross-linked hyaluronic acid , Chitosan, heparin, gelatin, elastin, hydrolyzed elastin, fibrin, laminin, fibronectin, proteoglycan, heparan sulfate, chondroitin sulfate, dermatan sulfate, and at least one selected from the group consisting of keratin sulfate, and the active ingredient is Cetearyl Olivate, Ethylhexyl Olivate, Arbutin, Japanese oak extract, Licorice extract, Sophora seed extract, Centella asiatica extract, White extract, Ethyl ascorbyl ether, Ascorbyl glucoside, Niacinamide, Magnesium Ascorbyl phosphate, ascorbic acid and its derivatives, kojic acid, glutathione, tyrosinase, diosmethine, mayslignan, vitamins and derivatives, asiaticoside, ubidecarenone, peony extract, polyethoxylated retinamide, hydride Roxyproline, retinoleic acid and its derivatives, alpha hydroic acid (AHA), adenosine, botox and its derivatives, hydroxypropyltrimodium hyaluronic acid, sodium caproyl hyaluronate, sodium oleoyl hyaluronate, sodium acetylray Tidhyaluronate; Rosemary, cloves, white porcelain, turmeric, green tea, black bean seeds, rose petals, peony root, bellflower, bean sprouts, colored barley seeds, camellia petals, buckwheat, grapefruit, licorice, yellow lotus, astragalus, hwangbaek, gold, cinnamon, grass, bokbunja, Dried hyaluronic acid system, characterized in that it is at least one selected from the group consisting of Obaeja, Juniper, Forsythia, Red Pepper Leaves, Peppermint, Snake Strawberry, Mulberry, Sambaekcho, Pine, Yakushikushi, Eoseongcho, Yoshino Cherry Blossom Tree, Choridae or Two Large Stem Extracts; The composition is provided.

In addition, the present invention provides a molded article comprising the dry hyaluronic acid-based composition.

According to the present invention, there is no toxicity, excellent product stability, excellent mechanical strength, short dissolution time, low stickiness, excellent feeling of use, and a method for preparing a dry hyaluronic acid-based composition in which the original performance of the active ingredient is well expressed and dry hyaluronic acid There is an effect of providing a Ronic acid-based composition.

1 is a schematic diagram schematically showing an embodiment of a freeze drying apparatus according to the present invention.
2 is a photograph of a sheet of a dry hyaluronic acid-based composition prepared in Examples 1 to 12.
3 is a photograph of a sheet of a dry hyaluronic acid-based composition prepared in Comparative Examples 1 to 7.
4 is a SEM photograph of the top and bottom surfaces of the dry hyaluronic acid-based composition sheets prepared in Example 1 and Comparative Example 1 at 50 times, 100 times and 500 times magnification, respectively.

Hereinafter, a method for preparing a dry hyaluronic acid-based composition and a dry hyaluronic acid-based composition of the present invention will be described in detail.

The inventors of the present invention are non-toxic and excellent product stability when multi-stage freezing and multi-stage drying of compositions containing heterogeneous natural hyaluronic acid compounds with different average molecular weights and hydrophilic polymers capable of forming van der Waals bonds with them And, it was confirmed that a dry hyaluronic acid-based composition was prepared with excellent mechanical strength, short dissolution time, low stickiness, and excellent usability, and the original performance of the active ingredient was well expressed. Was completed.

A detailed look at the method for preparing the dry hyaluronic acid-based composition of the present invention is as follows.

The method for preparing the hyaluronic acid-based composition of the present invention includes A) 44 to 93% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons, B) hyaluronic acid or hyaluronic acid salt having an average molecular weight of 100,000 Daltons or more A freezing step of freezing the hyaluronic acid-based composition containing 0.6 to 17% by weight and C) 1 to 50% by weight of a hydrophilic polymer at -1°C or less under normal pressure, and heating and drying the frozen hyaluronic acid-based composition under reduced pressure (Evacuation) The dried hyaluronic acid-based composition prepared in this way is non-toxic, has excellent product stability, has excellent mechanical strength, has a short dissolution time and has low stickiness, so it has excellent feeling of use. There is an effect that the performance of is well expressed.

The hyaluronic acid salt may be, for example, one or more selected from the group consisting of sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, cobalt hyaluronate, and tetrabutyl ammonium hyaluronate, and preferably It may be sodium hyaluronate, and in this case, it is more effective in skin care and wound healing.

The hyaluronic acid-based composition is preferably A) 44 to 93 wt% of hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons, B-1) hyaluronic acid or hyaluronic acid having an average molecular weight of 100,000 to 1,000,000 Daltons 0.5 to 12% by weight of laurate; B-2) 0.1 to 5% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of more than 1,000,000 Daltons, and C) 1 to 50% by weight of a hydrophilic polymer, within this range, has excellent mechanical strength, and is dissolved It has the advantage of excellent feeling of use due to short time and low stickiness.

The hyaluronic acid-based composition is preferably A) 44 to 93 wt% of hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons, B-1) hyaluronic acid or hyaluronic acid having an average molecular weight of 100,000 to 1,000,000 Daltons 0.5 to 12% by weight of laurate; B-2) 0.1 to 5% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,000,000 Daltons, and C) 100 parts by weight of a base polymer consisting of 1 to 50% by weight of a hydrophilic polymer; And 0.1 to 25 parts by weight of the active ingredient, and within this range, the mechanical strength is excellent, the dissolution time is short and the stickiness is small, so that the feeling of use is excellent, and the original performance of the active ingredient is well expressed.

The A) hyaluronic acid or hyaluronic acid salt may preferably have an average molecular weight of 3,000 to 50,000 Daltons, preferably 5,000 to 30,000 Daltons, more preferably 8,000 to 20,000 Daltons, and more preferably 80,000 to It may be 15,000 Daltons, and within this range, the penetration rate of the skin is high, so it is easy to deliver the active ingredient into the skin, so it has excellent advantages in skin care and wound treatment.

The A) hyaluronic acid or hyaluronic acid salt is preferably 45 to 75% by weight, more preferably 45 to 70% by weight, more preferably 50 to 65% by weight, even more preferably 50 to 60% by weight, Most preferably, it may be 53 to 56% by weight, and within this range, the penetration rate of the skin is high, so the delivery of active ingredients into the skin is easy, and the dissolution time of the dried hyaluronic acid-based composition is short and the stickiness is low, so the feeling of use is excellent. , It has the advantage of being suitable for cosmetic molded products that are applied to the skin by dissolving it in essences.

The B-1) hyaluronic acid or hyaluronic acid salt may preferably have an average molecular weight of 100,000 to 500,000 Daltons, preferably 150,000 to 300,000 Daltons, more preferably 150,000 to 250,000 Daltons, and more preferably It may be 200,000 to 250,000 Daltons, and within this range, mechanical properties, especially tensile strength, are excellent.

The B-1) hyaluronic acid or hyaluronic acid salt is preferably 1 to 12% by weight, more preferably 1 to 10% by weight, still more preferably 2 to 9% by weight, even more preferably 2 to 8% by weight %, most preferably 3 to 7% by weight, and within this range, mechanical properties, particularly tensile strength, are excellent.

The B-2) hyaluronic acid or hyaluronic acid salt may preferably have an average molecular weight of more than 1,000,000 Daltons to 3,000,000 Daltons or less, preferably 1,100,000 to 2,000,000 Daltons, more preferably 1,200,000 to 1,800,000 Daltons. And, more preferably, it may be 1,200,000 to 1,500,000 Daltons, and there is an excellent effect in the stability of the final dried hyaluronic acid-based composition product produced within this range.

The B-2) hyaluronic acid or hyaluronic acid salt is preferably 0.1 to 3% by weight, more preferably 0.5 to 2% by weight, even more preferably 0.5 to 1.5% by weight, even more preferably 0.6 to 1.4% by weight %, most preferably 0.8 to 1.2% by weight, there is an excellent effect of the stability of the final dried hyaluronic acid-based composition product produced within this range.

In the present invention, Dalton may be defined as 1/12 of the mass of one neutral ¹² C atom.

In the present invention, the average molecular weight is calculated by multiplying the molecular weight of each peak of hyaluronic acid and/or hyaluronic acid obtained by GPC measurement by the peak area, and the calculated value is accumulated for each of these peaks. In addition, the average molecular weight can be calculated by dividing this integrated value by the entire peak area.

The C) hydrophilic polymer is preferably maltodextrin, dextrin, guar gum, xantam gum, gum arabic, carboxymethylcellulose, agar, gum arabic, beta glucan, fluran, collagen, algin, crosslinked hyaluronic acid, crosslinked hyaluronic acid , Chitosan, heparin, gelatin, elastin, hydrolyzed elastin, fibrin, laminin, fibronectin, proteoglycan, heparan sulfate, chondroitin sulfate, dermatan sulfate and keratin sulfate, and may be one or more selected from the group consisting of, and within this range. The hyaluronic acid-based composition has excellent stability due to the interaction between components according to the van der Waals bond. In particular, the effect of stabilizing ultra-high molecular hyaluronic acid-based compounds such as B-2) hyaluronic acid or hyaluronic acid salt by mutual attraction such as van der Waals bond is great.

The C) hydrophilic polymer is preferably 10 to 50% by weight, more preferably 20 to 50% by weight, still more preferably 30 to 50% by weight, even more preferably 35 to 45% by weight, most preferably It may be 38 to 42% by weight, and within this range, the effect of stabilizing the hyaluronic acid-based composition is excellent by the interaction between the components according to the van der Waals bond.

The active ingredients are preferably cetearyl olivate, ethylhexyl olivate, hydroxypropyltrimodium hyaluronic acid, sodium caproyl hyaluronate, sodium oleoyl hyaluronate, Sodium acetylated hyaluronate, arbutin, mulberry extract, licorice extract, soybean seed extract, white extract, ethyl ascorbyl ether, ascorbyl glucoside, niacinamide, magnesium ascorbyl phosphate; Ascorbic acid and its derivatives; Kojic acid, glutathione, tyrosinase, diosmethine, mayslignan; Vitamins and derivatives thereof; Asiaticoside, ubidecarenone, peony extract, polyethoxylated retinamide, hydroxyproline, retinoleic acid and its derivatives, alpha hydroic acid (AHA), adenosine; Botox and its derivatives; Rosemary, cloves, white porcelain, turmeric, green tea, black bean seeds, rose petals, peony root, bellflower, bean sprouts, colored barley seeds, camellia petals, buckwheat, grapefruit, licorice, yellow lotus, astragalus, hwangbaek, gold, cinnamon, grass, bokbunja, Obaeja, juniper, forsythia, red pepper leaves, mint, snake strawberry, mulberry, sambaekcho, pine, wormwood, Eoseongcho, Yoshino cherry tree, botanical or two large stem extract; may be one or more selected from the group consisting of, in this case, dry hyaluronic acid There is an advantage in that the original performance of the active ingredient is well expressed without impairing the mechanical strength, solubility and feeling of use of the system composition.

The active ingredient is preferably 0.01 to 50 parts by weight, more preferably 0.05 to 30 parts by weight, even more preferably 0.05 to 25 parts by weight, even more preferably 0.1 to 20 parts by weight, most preferably 0.1 to 15 parts by weight. It may be parts by weight, and there is an advantage in that the original performance of the active ingredient is well expressed without impairing the mechanical strength, solubility and feeling of use of the dry hyaluronic acid-based composition within this range.

The hyaluronic acid-based composition preferably has a density of 10 to 30 g/L, preferably 15 to 25 g/L, more preferably 17 to 23 g/L, even more preferably 18 at room temperature or around 25°C. To 22 g/L, and within this range, the mechanical strength, solubility and feeling of use of the dry hyaluronic acid-based composition are all excellent. At this time, the density of the hyaluronic acid-based composition may be adjusted by the amount of water, preferably purified water, added to the components of the hyaluronic acid-based composition.

The freezing step is preferably a first freezing step of freezing the hyaluronic acid-based composition at -1 to -10 °C for 10 to 60 minutes under normal pressure; A second freezing step of reducing the temperature of the first frozen hyaluronic acid-based composition to -40 to -60°C for 1 to 10 hours under normal pressure; And a third freezing step of maintaining the second frozen hyaluronic acid-based composition at -40 to -60°C for 30 minutes to 5 hours under normal pressure, and the freezing efficiency is high within this range, and dry hyaluronic acid Ronic acid-based composition has excellent mechanical strength, short dissolution time and low stickiness, so it has the advantage of excellent feeling of use.

In this description, normal pressure is the pressure when the pressure is not specifically reduced or increased. It may refer to a pressure of about 1 atmosphere, such as the normal atmospheric pressure, and as a specific example, it may refer to a pressure in the range of 1 bar ± 300 Pa.

In a preferred embodiment, the freezing step comprises a first freezing step of freezing the hyaluronic acid-based composition at -3 to -8°C for 20 to 40 minutes under normal pressure; A second freezing step of reducing the temperature of the first frozen hyaluronic acid-based composition to -40 to -50°C for 5 to 9 hours under normal pressure; And a third freezing step of maintaining the second frozen hyaluronic acid-based composition at -40 to -50°C for 1 hour to 3 hours under normal pressure, and the freezing efficiency is high within this range. The dry hyaluronic acid-based composition has excellent mechanical strength, short dissolution time and low stickiness, so it has the advantage of excellent feeling of use.

The drying step is preferably a first drying step of stepwise or continuously raising the temperature of the frozen hyaluronic acid-based composition to 10 to 40 ℃ under 100 to 1,000 μbar for 5 to 30 hours; And a second drying step of drying the first dried hyaluronic acid-based composition under 1 to 99 μbar at 20 to 50° C. for 1 to 10 hours, and within this range, drying efficiency is high, and drying The hyaluronic acid-based composition has excellent mechanical strength, short dissolution time and low stickiness, so it has the advantage of excellent feeling of use.

In a preferred embodiment, the drying step comprises the steps of sequentially maintaining the frozen hyaluronic acid-based composition under 100 to 1,000 μbar at -40°C to -10°C or less for 2 to 6 hours; Maintaining the temperature above -10°C to -5°C for 2 to 6 hours; Maintaining the temperature above -5°C to 0°C for 2 to 6 hours; Maintaining for 30 minutes to 2 hours above 0 ℃ to 10 ℃ or less; Maintaining for 30 minutes to 2 hours at more than 10 ℃ to 20 ℃ or less; Maintaining for 30 minutes to 2 hours at more than 20 ℃ to 30 ℃ or less; And it may include the step of maintaining for 30 minutes to 2 hours at more than 30 ℃ to 45 ℃ or less, within this range, drying efficiency is high, the dry hyaluronic acid-based composition is excellent in mechanical strength, the dissolution time is short and sticky There is an advantage that it is less in terms of use and is excellent in feeling.

The method of preparing the hyaluronic acid-based composition may include the step of heating and stirring before the freezing as necessary to disperse it.

The heating and stirring may be performed at 5 to 50°C, preferably 10 to 25°C, for example.

In addition, the method for preparing the hyaluronic acid-based composition may optionally include filtering, sterilizing, or performing both after the dispersing step.

The filtering step may be performed using a microfilter having a pore size of 0.1 to 5 µm as an example, preferably a microfilter having a size of 0.3 to 1 µm, and more preferably It may be carried out using a microfilter of 0.5 to 0.8 ㎛ size.

In the present description, the diameter of the through hole may follow the definition generally accepted in the technical field of the microfilter, and may also follow the standard described in the commercially available microfilter product.

Each of the filtration and sterilization steps may be carried out under conditions of 20 to 25 °C and up to 5 bar as an example, preferably 20 to 25 °C and 1.5 to 3 bar, and more preferably 20 to 25 °C And it can be carried out at 2 to 3 bar.

The device used for lyophilization according to the present invention is not particularly limited if it is a device that can achieve the temperature and pressure conditions according to the present invention as a device commonly used in the technical field to which the present invention belongs. The (freezer) and vacuum dryer may be a separate freeze-drying device or a freeze-drying device, an integrated freeze-drying device in which a vacuum device and a heater are combined.

1 is a schematic diagram schematically showing an embodiment of a freeze drying apparatus according to the present invention. In this case, the lyophilization apparatus includes a vacuum chamber and a cooling apparatus connected thereto, and the vacuum chamber includes a cooling plate cooled by the cooling apparatus therein and a tray loaded thereon. The tray is filled with a solution of a hyaluronic acid-based composition to be lyophilized, and then, the solution of the hyaluronic acid-based composition is freeze-dried and dried under a predetermined pressure and temperature condition. The tray serves as a mold and can be changed according to the shape of the dry hyaluronic acid-based composition to be obtained, and preferably, the inside is partitioned to obtain a dry hyaluronic acid-based composition in a sheet form or a spherical dry hyaluronic acid composition. It may include a plurality of circular hollow structures to obtain a Ronic acid-based composition. For reference, in FIG. 1, a general configuration required for a freeze-drying device such as a heating device, a door, and a switch is omitted to clarify the technical features of the present invention, but it is obvious that a person skilled in the art can appropriately select such a configuration.

The dry hyaluronic acid-based composition of the present invention is preferably characterized in that it is prepared by the method for preparing a dry hyaluronic acid-based composition according to the present invention, and when prepared in this way, there is no toxicity, excellent product stability, excellent mechanical strength, and dissolution time It is short and has little stickiness, so it has excellent feeling of use, and has the effect of well expressing the original performance of the active ingredient.

In addition, the dry hyaluronic acid-based composition of the present invention is a preferred embodiment A) 44 to 93% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons, B-1) an average molecular weight of 100,000 to 1,000,000 Daltons ( Dalton) hyaluronic acid or hyaluronic acid salt 0.5 to 12% by weight; B-2) 0.1 to 5% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,000,000 Daltons, and C) 100 parts by weight of a base polymer consisting of 1 to 50% by weight of a hydrophilic polymer; And 0 to 25 parts by weight of an active ingredient, wherein the hyaluronic acid salt is selected from the group consisting of sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, cobalt hyaluronate, and tetrabutyl ammonium hyaluronate. At least one type, and the hydrophilic polymer is maltodextrin, dextrin, guar gum, xantam gum, gum arabic, carboxymethylcellulose, agar, gum arabic, beta glucan, fluran, collagen, algin, crosslinked hyaluronic acid, crosslinked hyaluronic acid , Chitosan, heparin, gelatin, elastin, hydrolyzed elastin, fibrin, laminin, fibronectin, proteoglycan, heparan sulfate, chondroitin sulfate, dermatan sulfate, and at least one selected from the group consisting of keratin sulfate, and the active ingredient is Cetearyl Olivate, Ethylhexyl Olivate, Hydroxypropyltrimodium Hyaluronic Acid, Sodium Caprooil Hyaluronate, Sodium Oleoyl Hyaluronate, Sodium Acetylated Hyaluronate Nate, arbutin, mulberry extract, licorice extract, sox seed extract, white extract, ethyl ascorbyl ether, ascorbyl glucoside, niacinamide, magnesium ascorbyl phosphate, ascorbic acid and its derivatives, kojic acid, glutathione, tyrosinase, diosmethine , Mayslignan, vitamins and derivatives thereof, asiaticoside, ubidecarenone, peony extract, polyethoxylated retinamide, hydroxyproline, retinoleic acid and its derivatives, alpha hydroic acid (AHA), adenosine, botox and Its derivatives; Rosemary, cloves, white porcelain, turmeric, green tea, black bean seeds, rose petals, peony root, bellflower, bean sprouts, colored barley seeds, camellia petals, buckwheat, grapefruit, licorice, yellow lotus, astragalus, hwangbaek, gold, cinnamon, grass, bokbunja, Obaeja, juniper, forsythia, pepper leaves, peppermint, snake strawberry, mulberry, sambaekcho, pine, mugwort, Eoseongcho, Yoshino cherry tree, Joritdae or two large stem extract; characterized in that at least one selected from the group consisting of. Such a dry hyaluronic acid-based composition is non-toxic, has excellent product stability, has excellent mechanical strength, has a short dissolution time and has low stickiness, so it has excellent feeling of use, and has the advantage of well expressing the original performance of the active ingredient.

The dry hyaluronic acid-based composition of the present invention includes all the technical features of the method for preparing the dry hyaluronic acid-based composition described above.

The dry hyaluronic acid-based composition is preferably A) 45 to 65% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons, B-1) hyaluronic acid having an average molecular weight of 100,000 to 1,000,000 Daltons or 1 to 15% by weight of hyaluronic acid salt; B-2) 0.5 to 2% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,000,000 Daltons, and C) 100 parts by weight of a base polymer consisting of 20 to 50% by weight of a hydrophilic polymer; And 0.1 to 25 parts by weight of the active ingredient, and within this range, the mechanical strength is excellent, the dissolution time is short and the stickiness is small, so that the feeling of use is excellent, and the original performance of the active ingredient is well expressed.

The dry hyaluronic acid-based composition is preferably A) hyaluronic acid having an average molecular weight of 7,000 to 20,000 Daltons or 45 to 65% by weight of hyaluronic acid salt, B-1) hyaluronic acid having an average molecular weight of 100,000 to 300,000 Daltons Or 1 to 15% by weight of hyaluronic acid salt; B-2) 0.5 to 2% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,100,000 to 1,800,000 Daltons and C) 100 parts by weight of a base polymer consisting of 20 to 50% by weight of a hydrophilic polymer; And 0.1 to 25 parts by weight of the active ingredient, and within this range, the mechanical strength is excellent, the dissolution time is short and the stickiness is small, so that the feeling of use is excellent, and the original performance of the active ingredient is well expressed.

The hyaluronic acid or hyaluronic acid salt of A), B-1) and B-2) may preferably be non-crosslinked hyaluronic acid or non-crosslinked hyaluronic acid salt, and in this case, there is no toxicity, and the dissolution time is short and sticky. It has an excellent feeling of use because it is small, and the original performance of the active ingredient is well expressed.

The dry hyaluronic acid-based composition may preferably be a freeze-dried hyaluronic acid-based composition, in this case, it has excellent mechanical strength, and the pores in the dry hyaluronic acid-based composition are homogeneous, so that the physical property balance is excellent, and the dissolution time is short and sticky. It has the advantage of being less comfortable to use.

The dry hyaluronic acid-based composition, for example, may have a moisture content of 10% by weight or less, preferably 2 to 10% by weight, more preferably 3 to 7% by weight, and has excellent product stability without alteration within this range, and moisture It has a fast melting effect.

In the present description, the moisture content can be measured by a method measured in the technical field to which the present invention belongs. For example, after drying the sample for 4 hours under 110 ℃ condition using an oven dryer and leaving the sample until there is no change in weight, It can be measured as a percentage by weight before drying.

The hyaluronic acid-based composition is, for example, 0.1 to 3 parts by weight, preferably 0.5, at least one selected from the group consisting of additives, emulsifiers, antioxidants, preservatives, moisturizers, and softening aids based on a total of 100 parts by weight of the hyaluronic acid-based composition. It may further contain 2 parts by weight, and in this case, the effect of improving the spreadability and product stability is excellent.

Examples of the additives include oil-soluble bases such as petrolatum, liquid paraffin, paraffin, plastibase, lard, vegetable oil, wax, refined lanolin, etc., water-soluble bases such as polyethylene glycol, absorption ointments, and emulsion bases such as hydrophilic ointments. have.

The emulsifier may include, for example, cetrimide such as sodium eulauryl sulfate (SLS), dioctyl sodium sulfosuccinate (DSS), benzalkonium chloride, benzethonium chloride, trimethyltetradecylammonium bromide; Esters per fatty acid; Glyceryl monooleate; Polyoxyethylene sorbitan fatty acid esters; Dimethylpolysiloxane; Sorbitan esters; And it may be one or more selected from the group consisting of lecithin.

Examples of the preservatives include 1,2-butanediol paraoxybenzoic acid esters, quaternium-15, imidazolidinyl urea, phenoxyethanol, benzalkonium chloride, chlorohexidine gluconate, and triclosan. It may be one or more selected from the group consisting of.

The molded article of the present invention is characterized in that it contains the dry hyaluronic acid-based composition of the present invention.

The molded article may preferably be a cosmetic product, more preferably a cosmetic molded article that can be dissolved and used in an essence, etc., in this case, it has low stickiness and excellent feeling of use, and the skin penetration rate is high, so that the delivery of active ingredients into the skin is possible. It is easy and effective for skin care.

For example, the cosmetic is 1 selected from the group consisting of skin, lotion, cream, essence, sunscreen, cleansing agent, foundation, lipstick, lip gloss, lip tint, mascara, eyeliner, eyebrow, shadow, mask pack and patch. It may be more than one species, and preferably may be a skin, lotion, cream or essence.

In addition, the molded article may be another example of a dental implant, an orthopedic implant, a cell support, or a drug delivery system.

Hereinafter, a preferred embodiment is presented to aid the understanding of the present description, but the following examples are only illustrative of the present description, and that various changes and modifications are possible within the scope of the present description and the scope of the technical idea will be apparent to those skilled in the art, It is natural that such modifications and modifications fall within the appended claims.

[Example]

Components used in the following Examples and Comparative Examples are as follows.

* (A): Sodium hyaluronate with an average molecular weight of 10,000 Daltons

* (A)': Hyaluronic acid sodium salt with an average molecular weight of 5,000 Daltons

* (B-1): Sodium hyaluronate with an average molecular weight of 220,000 Daltons

* (B-1)': Sodium hyaluronate with an average molecular weight of 200,000 Daltons

* (B-2): Sodium hyaluronate with an average molecular weight of 1,400,000 Daltons

* (C): a mixture of algin and hydrolyzed collagen (weight ratio 1:3)

* (C)': Hydrolyzed collagen

* (C)": hyaluronic acid crosspolymer

* (D): Ethylhexylolivate (olive oil PEG-7 ester; olive oil fatty acid and PEG weight ratio 4:1)

* (D)': hydroxypropyltrimodium hyaluronic acid

* (D)": bottle extract

Examples 1 to 12 and Comparative Examples 1 to 7

A composition solution was prepared and completely dissolved in purified water of a standard volume (amount to make the density of the composition solution 20 g/L) at room temperature around 25° C. with the components and contents shown in Tables 1 and 2 below.

For each prepared composition solution, 2 mL each was dispensed into a flat mold (inner size 2 cm X 2 cm) or 1 mL each in a spherical mold (inner diameter size 12 mm), and lyophilized under the conditions of Table 3 below using a lyophilization apparatus as shown in FIG. Sheet-type and old-type freeze-dried hyaluronic acid-based compositions were prepared.

[Test Example]

The properties of the sheet-type and old-type freeze-dried hyaluronic acid-based compositions prepared in Examples 1 to 12 and Comparative Examples 1 to 7 were measured in the following manner, and the results are shown in Tables 4 and 5 and FIGS. It is shown in 4.

* Compressive strength (N): According to ASTM D695 standard, the prepared spherical dry hyaluronic acid-based composition was subjected to a compression test at a rate of 2 mm/min to evaluate the compressive strength. The compressive strength (N) was calculated using the measured results by moving the jig to a position at 50% of the initial size of the specimen.

* Adhesion (N): Referring to ASTM D2979 standard, 0.5 g of a solution obtained by dissolving the prepared dry hyaluronic acid-based composition at a concentration of 20 mg/ml was subjected to a TACK test at a rate of 1.25 mm/min to evaluate stickiness due to the adhesive strength of the solution. .

* Sheet compressive strength (N, 3 point bending test):

The prepared sheet-shaped dry hyalusonic acid-based composition was mounted on a jig to measure the bending strength (N) and Young's modulus (MPa). The compression speed was 20 mm/min, and the test values were measured until the specimen was fractured, and the bending strength (N) and Young's modulus (MPa) were calculated using the results.

* Pore shape: The surface of the prepared dry hyaluronic acid-based composition was coated at a low temperature, and the pore shape was analyzed using a scanning electron microscope (SEM).

* Melting time (solubility): After sufficiently filling a container in which the hyaluronic acid-based composition can be immersed, the hyaluronic acid-based composition was dropped onto water and the time to completely dissolve was measured and evaluated.

* Appearance characteristics: When the sheet-type dry hyaluronic acid composition is bent, cracked or there is no layer separation, it was evaluated as good.

division (A)
HA less than 100,000 Da (B-1)
200,000-400,000 Da HA (B-2)
HA over 1 million Da (C) hydrophilic polymer (D) active ingredient (C) (C)' (C)" (D) (D)' (D)" Example 1A 54 5 One 40 - - - - - Example 1B 54 5 One - 40 - - - - Example 2A 68.5 0.5 One 30 - - - - - Example 2B 68.5 0.5 One - 30 - - - - Example 3A 57 12 One 30 - - - - - Example 3B 57 12 One - 30 - - - - Example 4A 64.9 5 0.1 30 - - - - - Example 4B 64.9 5 0.1 - 30 - - - - Example 5A 60 5 5 30 - - - - - Example 5B 60 5 5 - 30 - - - - Example 6A 93 5 One One - - - - - Example 6B 93 5 One - One - - - - Example 7A 74 5 One 20 - - - - - Example 7B 74 5 One - 20 - - - - Example 8A 44 5 One 50 - - - - - Example 8B 44 5 One - 50 - - - - Example 9 93 5 One - - One - - - Example 10 54 5 One 40 - - 15 - - Example 11 54 5 One 40 - - - One - Example 12 54 5 One 40 - - - - 0.1

division (A)
100,000 Da
Less than HA (B-1)
200,000-400,000
Da HA (B-2)
1 million Da
More than ha (C) hydrophilic polymer (C) (C)' (C)" Comparative Example 1 100 - - - - - Comparative Example 2 88 12 - - - - Comparative Example 3 95 - 5 - - - Comparative Example 4A 50 - - 50 - - Comparative Example 4B 50 - - - 50 - Comparative Example 5A 30 9 One 60 - - Comparative Example 5B 30 9 One - 60 - Comparative Example 6A 43 5 One 51 - - Comparative Example 6B 43 5 One - 51 - Comparative Example 7A 93.5 5 One 0.5 - - Comparative Example 7B 93.5 5 One - 0.5 -

division Freeze drying conditions Remark Temperature Pressure (μbar) time Stage 1 -6 Normal pressure 0.5 maintain Step 2 -6 → -45 Normal pressure 7 Over 7 hours
Temperature drop Step 3 -45 Normal pressure 2 maintain Step 4 -10 300 4 maintain Step 5 -5 300 4 maintain Step 6 0 300 4 maintain Step 7 10 300 One maintain Step 8 20 300 One maintain Step 9 30 300 One maintain Step 10 40 30 3 maintain

division Compression strength (old type)(N, 6mm) Appearance characteristics (sheet type) Example 1A 2.32276 Good Example 1B 2.795824 Good Example 2A 2.270396 Good Example 2B 2.226266 Good Example 3A 2.495998 Good Example 3B 3.557536 Good Example 4A 2.603168 Good Example 4B 3.0893 Good Example 5A 2.868086 Good Example 5B 5.374234 Good Example 6A 2.47773 Good Example 6B 3.729672 Good Example 7A 2.272998 Good Example 7B 2.383932 Good Example 8A 2.82674 Good Example 8B 2.557668 Good Example 9 2.38466 Good Example 10 2.22196 Good Example 11 2.60439 Good Example 12 2.71701 Good

division Compression strength (old type)
(N, 6mm) Appearance characteristics (sheet type) Comparative Example 1 0.767808 Bending Comparative Example 2 1.329912 offshoot Comparative Example 3 2.0084 Bending Comparative Example 4A 1.608444 offshoot Comparative Example 4B 1.363202 offshoot Comparative Example 5A 3.01815 Bending Comparative Example 5B 3.155728 Bending Comparative Example 6A 2.59727 Cracking/Lamination Comparative Example 6B 3.285788 offshoot Comparative Example 7A 2.968036 offshoot Comparative Example 7B 2.554386 offshoot

As shown in Tables 4 and 5, the dry hyaluronic acid-based composition (Examples 1 to 12) according to the present invention is compared to the dry hyaluronic acid-based composition prepared in Comparative Examples 1 to 7, mechanical strength and appearance such as compressive strength, etc. It has excellent characteristics, short melting time, and low stickiness, so it is suitable for cosmetics, implants, or drug delivery systems, and is particularly suitable for cosmetic molded articles applied to the skin and absorbed into the skin.

In addition, the dry hyaluronic acid-based composition according to the present invention (Examples 1 to 12) had a sheet compressive strength (N, 3 point bending) of 0.45 N or more, specifically 0.45 to 1.94 N, and a sheet elastic modulus (3 point bending). This was 0.15 or more, specifically within the range of 0.15 to 0.93, the melting time (decomposition time) was within 30 seconds, specifically within the range of 2 to 28 seconds, and it was confirmed that the adhesive strength was within the range of 3.5 to 10.5 N, Comparative Example And it was confirmed that the balance of all physical properties was excellent compared to the prior art.

Referring to FIGS. 2 and 3 below, the dry hyaluronic acid-based composition (Examples 1 to 12) according to the present invention has no warping, cracking, or layer separation compared to the dry hyaluronic acid-based composition prepared in Comparative Examples 1 to 7 It was confirmed that the characteristics were excellent.

In addition, referring to FIG. 4 below, the dry hyaluronic acid-based composition according to the present invention (Example 1) has open pores on the top surface as compared to the dry hyaluronic acid-based composition (Comparative Example 1) not according to the present invention. It was confirmed that the homogeneity of pores was excellent on both the upper and lower surfaces.

Claims (15)

A) 44 to 93 wt% of hyaluronic acid or hyaluronic acid having an average molecular weight of less than 100,000 Daltons, B) 0.6 to 17 wt% of hyaluronic acid or hyaluronic acid having an average molecular weight of 100,000 Daltons or more and C) Hydrophilic polymer 1 A freezing step of freezing the hyaluronic acid-based composition comprising to 50% by weight at -1° C. or less under normal pressure, and a drying step of heating and drying the frozen hyaluronic acid-based composition under reduced pressure (Evacuation).
Method for producing a dry hyaluronic acid-based composition. The method of claim 1,
The hyaluronic acid-based composition is A) 44 to 93% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons, B-1) hyaluronic acid or hyaluronic acid salt having an average molecular weight of 100,000 to 1,000,000 Daltons 0.5 To 12% by weight; B-2) characterized by comprising 0.1 to 5% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,000,000 Daltons and C) 1 to 50% by weight of a hydrophilic polymer
Method for producing a dry hyaluronic acid-based composition. The method of claim 1,
The hyaluronic acid-based composition is A) 44 to 93% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons, B-1) hyaluronic acid or hyaluronic acid salt having an average molecular weight of 100,000 to 1,000,000 Daltons 0.5 To 12% by weight; B-2) 0.1 to 5% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,000,000 Daltons, and C) 100 parts by weight of a base polymer consisting of 1 to 50% by weight of a hydrophilic polymer; And 0.1 to 25 parts by weight of an active ingredient.
Method for producing a dry hyaluronic acid-based composition. The method of claim 1,
The freezing step includes a first freezing step of freezing the hyaluronic acid-based composition at -1 to -10°C for 10 to 60 minutes under normal pressure; A second freezing step of reducing the temperature of the first frozen hyaluronic acid-based composition to -40 to -60°C for 1 to 10 hours under normal pressure; And a third freezing step of maintaining the second frozen hyaluronic acid-based composition at -40 to -60°C for 30 minutes to 5 hours under normal pressure.
Method for producing a dry hyaluronic acid-based composition. The method of claim 1,
The drying step includes a first drying step of gradually or continuously raising the temperature of the frozen hyaluronic acid-based composition to 10 to 40° C. under 100 to 1,000 μbar for 5 to 30 hours; And a second drying step of drying the first dried hyaluronic acid-based composition under 1 to 99 μbar at 20 to 50° C. for 1 to 10 hours; characterized in that it comprises
Method for producing a dry hyaluronic acid-based composition. The method of claim 1,
The hydrophilic polymers include maltodextrin, dextrin, guar gum, xantham gum, gum arabic, carboxymethylcellulose, agar, gum arabic, beta glucan, fluran, collagen, algin, cross-linked hyaluronic acid, cross-linked hyaluronic acid, chitosan, heparin, Characterized in that at least one selected from the group consisting of gelatin, elastin, hydrolyzed elastin, fibrin, laminin, fibronectin, proteoglycan, heparan sulfate, chondroitin sulfate, dermatan sulfate, and keratin sulfate.
Method for producing a dry hyaluronic acid-based composition. The method of claim 3,
The active ingredients are Cetearyl Olivate, Ethylhexyl Olivate, Hydroxypropyltrimodium Hyaluronic Acid, Sodium Caproyl Hyaluronate, Sodium Oleoyl Hyaluronate, Sodium Acetyl Ray Tid hyaluronate, arbutin, mulberry extract, licorice extract, sox seed extract, white extract, ethyl ascorbyl ether, ascorbyl glucoside, niacinamide, magnesium ascorbyl phosphate, ascorbic acid and its derivatives, kojic acid, glutathione, Tyrosinase, diosmethine, mayslignan, vitamins and their derivatives, asiaticoside, ubidecarenone, peony extract, polyethoxylated retinamide, hydroxyproline, retinolic acid and its derivatives, alpha hydroic acid (AHA), Adenosine, botox and derivatives thereof; Rosemary, cloves, white porcelain, turmeric, green tea, black bean seeds, rose petals, peony root, bellflower, bean sprouts, colored barley seeds, camellia petals, buckwheat, grapefruit, licorice, yellow lotus, astragalus, hwangbaek, gold, cinnamon, grass, bokbunja, Obaeja, juniper, forsythia, red pepper leaves, mint, snake strawberry, mulberry, sambaekcho, pine, mugwort, Eoseongcho, Yoshino cherry tree, chorizo or two large stem extract; characterized in that at least one selected from the group consisting of
Method for producing a dry hyaluronic acid-based composition. It is characterized in that it is prepared by the method for preparing a dry hyaluronic acid-based composition according to any one of claims 1 to 7
Dry hyaluronic acid-based composition. A) 44 to 93% by weight of hyaluronic acid or hyaluronic acid having an average molecular weight of less than 100,000 Dalton, B-1) 0.5 to 12% by weight of hyaluronic acid or hyaluronic acid having an average molecular weight of 100,000 to 1,000,000 Daltons; B-2) 0.1 to 5% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,000,000 Daltons, and C) 100 parts by weight of a base polymer consisting of 1 to 50% by weight of a hydrophilic polymer; And 0 to 25 parts by weight of an active ingredient,
The hyaluronic acid salt is at least one selected from the group consisting of sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, cobalt hyaluronate, and tetrabutyl ammonium hyaluronate,
The hydrophilic polymers include maltodextrin, dextrin, guar gum, xantham gum, gum arabic, carboxymethylcellulose, agar, gum arabic, beta glucan, fluran, collagen, algin, cross-linked hyaluronic acid, cross-linked hyaluronic acid, chitosan, heparin, Gelatin, elastin, hydrolyzed elastin, fibrin, laminin, fibronectin, proteoglycan, heparan sulfate, chondroitin sulfate, dermatan sulfate, and at least one selected from the group consisting of keratin sulfate,
The active ingredients are Cetearyl Olivate, Ethylhexyl Olivate, Hydroxypropyltrimodium Hyaluronic Acid, Sodium Caproyl Hyaluronate, Sodium Oleoyl Hyaluronate, Sodium Acetyl Ray Tied hyaluronate, arbutin, mulberry extract, licorice extract, sox seed extract, white extract, ethyl ascorbyl ether, ascorbyl glucoside, niacinamide, magnesium ascorbyl phosphate, ascorbic acid and its derivatives, kojic acid, glutathione, Tyrosinase, diosmethine, mayslignan, vitamins and their derivatives, asiaticoside, ubidecarenone, peony extract, polyethoxylated retinamide, hydroxyproline, retinolic acid and its derivatives, alpha hydroic acid (AHA), Adenosine, botox and derivatives thereof; Rosemary, cloves, white porcelain, turmeric, green tea, black bean seeds, rose petals, peony root, bellflower, bean sprouts, colored barley seeds, camellia petals, buckwheat, grapefruit, licorice, yellow lotus, astragalus, hwangbaek, gold, cinnamon, grass, bokbunja, Obaeja, juniper, forsythia, red pepper leaves, mint, snake strawberry, mulberry, sambaekcho, pine, wormwood, eoseongcho, Yoshino cherry tree, bovine or two large stem extract; characterized in that at least one selected from the group consisting of
Dry hyaluronic acid-based composition. The method of claim 9,
The dry hyaluronic acid-based composition is A) 45 to 65% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of less than 100,000 Daltons, B-1) hyaluronic acid or hyaluronic acid having an average molecular weight of 100,000 to 1,000,000 Daltons 1 to 15% by weight; B-2) 0.5 to 2% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,000,000 Daltons, and C) 100 parts by weight of a base polymer consisting of 20 to 50% by weight of a hydrophilic polymer; And 0.1 to 25 parts by weight of an active ingredient.
Dry hyaluronic acid-based composition. The method of claim 9,
The dry hyaluronic acid-based composition is A) hyaluronic acid or hyaluronic acid having an average molecular weight of 7,000 to 20,000 Daltons or 45 to 65% by weight of hyaluronic acid salt, B-1) an average molecular weight of 100,000 to 300,000 Daltons 1 to 15% by weight of acid salt; B-2) 0.5 to 2% by weight of hyaluronic acid or hyaluronic acid salt having an average molecular weight of 1,100,000 to 1,800,000 Daltons and C) 100 parts by weight of a base polymer consisting of 20 to 50% by weight of a hydrophilic polymer; And 0.1 to 25 parts by weight of an active ingredient.
Dry hyaluronic acid-based composition. The method of claim 9,
The hyaluronic acid or hyaluronic acid salt of A), B-1) and B-2) is non-crosslinked hyaluronic acid or non-crosslinked hyaluronic acid salt.
Dry hyaluronic acid-based composition. The method of claim 9,
The dried hyaluronic acid-based composition is characterized in that the freeze-dried hyaluronic acid-based composition
Dry hyaluronic acid-based composition. It comprises a dry hyaluronic acid-based composition according to any one of claims 9 to 13, characterized in that
Molded products. The method of claim 14,
The molded article is characterized in that it is a cosmetic molded article melted and used in cosmetics or essence
Molded products.

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