KR101631110B1 - Nano structure and a method for producing the same - Google Patents

Abstract

       The present invention relates to a glycosaminoglycan nanostructure and a method for producing the same, wherein the glycosaminoglycan nanostructure according to the present invention absorbs moisture rapidly upon dissolution through stepwise cooling and drying without adding a crosslinking agent, It maintains the state of gel with high viscous content, has excellent properties of mass transfer and maintains moisture retention for a long time.

Description

       [0001] NANO STRUCTURE AND METHOD FOR PRODUCING THE SAME [0002]

The present invention relates to a nanostructure and a method for producing the same.

A soluble glycosaminoglycan hydrogel or a sponge form prepared by a conventional method is added with a crosslinking agent to prevent the glycosaminoglycan from being easily broken or dissolved and dispersed to cause a crosslinking reaction to form irregular Which is crosslinked in a pattern to collect moisture in the form of a gel without being hydrated in the form of a sol, or a formulation made in the form of a sponge freeze-dried in the form of a freeze-dried hydrogel. Formulations of hyaluronic acid produced by cross-linking reactions can have a negative impact on the maintenance of mass transfer or moisturization to the human body. Korean Patent Laid-Open No. 10-2009-0013696 discloses a process for producing a hyaluronic acid crosslinked hydrogel by reacting hyaluronic acid or a salt thereof or a derivative thereof with a dihydrazide compound of an aliphatic dicarboxylic acid in the presence of a carboxyl group activating agent in a water- And a method of manufacturing the same. Lou et al. First made hyaluronic acid as an adipic dihydrazide derivative and then added it to a polyethylene glycol solution (hereinafter referred to as " adipic < RTI ID = 0.0 > dihydrazide & -Propionic < / RTI > aldehyde is used to make hyaluronic acid as a cross-linked hydrogel.

In order to solve the above problems, a glycosaminoglycan nanostructure having solubility characteristics was prepared by freezing and drying in different conditions without causing a crosslinking reaction.

     Numerous cited documents and patent documents are referred to and cited throughout this specification. The disclosures of the cited documents and patents are incorporated herein by reference in their entirety to more clearly describe the state of the art to which the present invention pertains and the content of the present invention.

The present invention provides a glycosaminoglycan nanostructure and a method for producing the same.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

Various embodiments described herein are described with reference to the drawings. In the following description, for purposes of complete understanding of the present invention, various specific details are set forth, such as specific forms, compositions, and processes, and the like. However, certain embodiments may be practiced without one or more of these specific details, or with other known methods and forms. In other instances, well-known processes and techniques of manufacture are not described in any detail, in order not to unnecessarily obscure the present invention. Reference throughout this specification to "one embodiment" or "embodiment" means that a particular feature, form, composition, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. Accordingly, the appearances of the phrase " in one embodiment "or" the embodiment "in various places throughout this specification are not necessarily indicative of the same embodiment of the present invention. In addition, a particular feature, form, composition, or characteristic may be combined in any suitable manner in one or more embodiments.

In one embodiment, there is provided a method comprising: forming a glycosaminoglycan mixture from a reactant glycosaminoglycan; Cooling the glycosaminoglycan mixture to room temperature to -14 占 폚 to prepare a primary cooling product; Cooling the glycosaminoglycan mixture to a temperature of -14 DEG C to -45 DEG C to prepare a secondary cooling product; And drying the secondary cooling product. The present invention also provides a method for producing a glycosaminoglycan nanostructure.

In one embodiment of the present invention, glycosaminoglycan refers to a polysaccharide having a disaccharide unit of hexosamine and uronic acid or galactose as a basic structure. For example, it is not limited to this, and it is composed of at least one selected from the group consisting of hyaluronic acid, chondroitin, chondroitin sulfate A, chondroitin sulfate C, termatan sulfate, heparin, heparin sulfate and keratin sulfate.

In one embodiment, the glycosaminoglycan is at least one selected from the group consisting of hyaluronic acid, chondroitin, chondroitin sulfate A, chondroitin sulfate C, termatan sulfate, heparin, heparin sulfate and keratan sulfate. A method for producing a nanoglycan nanostructure is provided. In this embodiment, the glycosaminoglycan is a hyaluronic acid, wherein the hyaluronic acid is a mixture of N-acetylglucosamine and glucuronic acid in the form of alternating chains and has a molecular weight of 1,000 - 2,000 kDa of glycosaminoglycan nanostructure.

In one embodiment, the glycosaminoglycan mixture comprises a sugar alcohol and a glycosaminoglycan in a weight ratio of from 0.1: 1 to 1: 1. In this embodiment, the sugar alcohol is selected from the group consisting of D-dulcitol, D-sorbitol, and D-mannitol, and a method for producing the glycosaminoglycan nanostructure is provided do.

In one embodiment of the present invention, the sugar alcohol refers to a polyhydric alcohol in which an aldehyde group or a ketone group of a sugar is reduced to form a first or second alcohol group, respectively. But is not limited to, for example, at least one selected from the group consisting of D-dulcitol, D-mannitol and D-sorbitol.

In one embodiment, the cooling step provides a method of making a glycosaminoglycan nanostructure comprising a first cooling step of cooling to room temperature to -14 占 폚 and a second cooling step of cooling to -45 占 폚 at -14 占 폚 . In this embodiment, the primary cooling step is carried out at room temperature by 1 to 2 DEG C per hour, reaching -10 DEG C and then having a heat-shrinkage period, followed by cooling down to -14 DEG C And the second cooling step is carried out at a temperature of -14 DEG C per 1 DEG C to 2.5 DEG C per hour to reach -45 DEG C. The present invention also provides a method for producing a glycosaminoglycan nanostructure.

In one embodiment, there is provided a method for preparing a glycosaminoglycan nanostructure comprising the step of drying a secondary cooling product. In the above embodiment, the drying step includes a drying step using a sublimation reaction using a vacuum pump for the secondary cooling; And drying by temperature elevation. In this embodiment, the temperature raising and drying step is carried out at a temperature of -45 DEG C to a temperature of 5 DEG C to 10 DEG C To a temperature of 20 占 폚.

In one embodiment, there is provided a glycosaminoglycan nanostructure characterized in that it is prepared from a mixture of glycosaminoglycan and sugar alcohol through a first cooling step, a second cooling step, and a drying step. The first cooling step includes a deodorizing process, and the first cooling step and the second cooling step also include a deodorizing process. Rapid cooling or drying without any secondary heat during the cooling process results in not only homogenization but also cracking, resulting in an area of more than 12 mm 2, which is difficult to commercialize. FIG. 3 is a comparative photograph of the rapid freezing and rapid drying without the left-handed section and the comparison with the method of the present invention on the right.

In one embodiment, the glycosaminoglycan nanostructure to which the sugar alcohol is added and the glycosaminoglycan nanostructure to which the sugar alcohol is not added were produced by the above production method, and as a result, the water content of the glycosaminoglycan nanostructure The glycosaminoglycan nanostructures to which the sugar alcohol is added in the structure are better dried in water. In the case of the water solubility (g / L), which is the amount of the nanostructures per 1 L of water, it was confirmed that the glycosaminoglycan nanostructure dissolves irrespective of the addition of sugar alcohol.

In one embodiment, the glycosaminoglycan nanostructure to which sugar alcohol is added and the glycosaminoglycan nanostructure to which sugar alcohol is not added were produced by the above-mentioned production method, and as a result, glycosaminoglycan The glycosaminoglycan nanostructures to which the sugar alcohol was added as compared to the glycan nanostructures were measured to have a high tensile load.

In one embodiment, a cosmetic comprising the glycosaminoglycan nanostructure and the active ingredient can be made. There is provided a cosmetic or cosmetic composition containing the above-mentioned glycosaminoglycan nanostructure itself or a composition obtained by mixing a cosmetically acceptable carrier with a functional ingredient, wherein the cosmetic or cosmetic is a lotion, a nutritional lotion, a nutritional cream, a massage cream , A pack and a nutritional essence. Here, the method of manufacturing a cosmetic product of the above-described form and the coating material are obvious to those skilled in the art, and detailed description of the manufacturing method will be omitted.

In one embodiment, the cosmetic composition containing the glycosaminoglycan nanostructure and the active ingredient may exhibit an effect of improving the skin color by directly transferring a cosmetic active ingredient to the skin. The cosmetic active ingredient may be composed of, for example, any one or more selected from the group consisting of Rosehip seed oil, Panthenol, Niacinamide, and the like, but is not limited thereto.

In one embodiment, a wound treatment agent comprising a glycosaminoglycan nanostructure and an active ingredient can be made. When the wound treatment agent is used in a place where a wound occurs, an excellent wound treatment effect is obtained by directly transferring the skin regenerated protein. The skin regeneration protein refers to an EGF component or the like, but is not limited thereto.

The glycosaminoglycan nanostructure according to the present invention is prepared through primary cooling, secondary cooling and drying without addition of a crosslinking agent, and is capable of absorbing moisture quickly upon dissolution and having a high viscosity Maintain gel state. Thus, a glycosaminoglycan nanostructure can be produced which has characteristics that mass transfer is excellent and moisture retention is maintained for a long time.

Figure 1 relates to a manufacturing process diagram.
Fig. 2 is a photograph showing the properties of the soluble glycosaminoglycan nanostructure.
Fig. 3 is a photograph of the properties of the glycosaminoglycan nanostructure in the case of rapid freezing and rapid drying on the left, which is freeze-dried in accordance with the method of the present invention on the right.
FIG. 4 is a photograph showing the properties of the glycosaminoglycan nanostructure added with no sugar alcohol on the right and the glycosaminoglycan nanostructure added on the left.

Hereinafter, the present invention will be described in more detail with reference to Examples. It will be apparent to those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Sugar alcohol-added Glycosaminoglycan  Comparison of properties for nanostructures

Comparative Example

     [ Example  One]

Glycosaminoglycan  Manufacture of nanostructures

[Production Example 1]

The hyaluronic acid powder having a molecular weight of 1,000 to 2,000 kDa was added to purified water so as to have a concentration of 0.02 M and uniformly mixed using a mixing mixer at a speed of 400 to 500 rpm. The hyaluronic acid aqueous solution was uniformly poured into an aluminum dish or a plastic dish (polystyrene material) made of a steel use stainless steel so as to have a concentration of 100 to 600 ul per cm 2 or 250 ul per cm 2.

The plastic plate was first cooled to < RTI ID = 0.0 > 10 C < / RTI > The primary cooling process is to decrease the temperature by 0.5 to 0.8 deg. C for 20 to 40 minutes to reach -10 deg. C (1-2 deg. C / hr) and then to the temperature at -10 deg. C for 1.5 to 2.5 hours Lt; 0 > C (2-2.5 [deg.] C / hr). The tertiary cooling process allowed the temperature to decrease to -45 占 폚 at -14 占 폚 (2.5-3 占 폚 / hr).

After being completely cooled, it was sublimated by a vacuum pump, and moisture in the aqueous solution of hyaluronic acid was primarily dried. In addition, the temperature was increased stepwise at intervals of about 1 hour from -45 ° C to 5 ° C to 10 ° C, or gradually increased to 20 ° C, followed by rapid secondary drying (5-10 ° C / hr ), A nanostructure was obtained.

      [Production Example 2]

The same procedure as in Preparation Example 1 was carried out except that a mixture of an aqueous solution of hyaluronic acid and a 0.02 M concentration of D-mannitol in a 0.7: 0.3 weight ratio was used.

      [Control 1]

The same procedure as in Preparation Example 1 was followed except that the primary cooling step was cooled to -14 占 폚 at 4 占 폚 / hr and the secondary cooling step was cooled to 5 占 폚 / hr, followed by cooling in a single step.

      [Control group 2]

The same procedure as in Production Example 1 was carried out except that the primary and secondary cooling processes were cooled in a single process at 5 ° C / hr.

      [Control 3]

The same procedure as in Preparation Example 1 was carried out except that the secondary drying step was carried out at a rate of 5 ° C / hr without drying by sublimation with a vacuum pump.

[ Example  2]

Glycosaminoglycan  Evaluation of physical properties of nanostructures

The physical properties of the preparation method according to Preparation Example 2 and the control group are shown in Table 1 below.

Production Example 2 Control 1 Control group 2 Control group 3 Homogeneity O X X X Whether cracks occur when the area is enlarged O X X X

(O means homogeneous, cracking does not occur when the area is enlarged, X indicates inhomogeneity, and cracks are generated when the area is enlarged.)

The physical properties of the nanostructures of Production Examples 1 and 2 are shown in Tables 2 and 3 below.

division Moisture content Water solubility The nanostructure according to Production Example 1 13.8 O The nanostructure according to Production Example 2 7.18 O

(O means 1 g of sample is dissolved in 10 ml of water.)

The water content was measured by how long the absorbed moisture was contained by the Kafiash method. The water solubility was measured by measuring the weight of the sponge dissolved per liter of water, and measuring the water solubility in g / L.

division Tensile load (N) Production Example 1 18.31 Production Example 2 95.76

Tensile strength is measured by tensile strength, tensile elastic modulus, yield strength, elongation, SS (stress-strain) curve by using universal testing machine (UTM), KS, JIS, ISO and ASTM Respectively.

     While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

Claims (16)

Starting the glycosaminoglycan mixture from 10 占 폚 to 30 占 폚 to prepare a primary coolant at a rate of 1 to 2 占 폚 / hr at -8 to -10 占 폚;
Cooling the primary cooling product at a rate of from 2.5 to 3 캜 / hr from -45 캜 to -55 캜 to prepare a secondary cooling product; And
And raising the secondary cooling product to a temperature of 10 ° C to 30 ° C at a stepwise temperature of 5 ° C to 10 ° C at a stepwise interval of 0.5-1.5 hours, followed by drying, thereby producing a glycosaminoglycan nanostructure.
The method according to claim 1,
Wherein the glycosaminoglycan mixture further comprises a saccharide alcohol.
The method according to claim 1,
Wherein the glycosaminoglycan is at least one selected from the group consisting of hyaluronic acid, chondroitin, chondroitin sulfate A, chondroitin sulfate C, desmartan sulfate, heparin, heparin sulfate and keratan sulfate.
The method of claim 3,
The glycosaminoglycan is a hyaluronic acid glycosaminoglycan nanostructure production method
5. The method of claim 4,
Wherein said hyaluronic acid is a nanostructure production method in which N-acetylglucosamine and glucuronic acid are alternately formed in a chain form
5. The method of claim 4,
Wherein the hyaluronic acid is a glycosaminoglycan nanostructure production method with a molecular weight of 1,000 to 2,000 kDa
3. The method of claim 2,
Wherein the weight ratio of the glycosaminoglycan and the sugar alcohol is 1: 0.1 to 1: 1; and a method for producing the glycosaminoglycan nanostructure
8. The method of claim 7,
Wherein the sugar alcohol is at least one selected from the group consisting of D-dulcitol, D-sorbitol, and D-mannitol; and a method for producing a glycosaminoglycan nanostructure
delete The method according to claim 1,
Wherein the step of preparing the primary cooling step comprises cooling the cooling water at -8 DEG C to -10 DEG C at a rate of 2 to 2.5 DEG C / hr to a temperature of -12 DEG C to -14 DEG C, wherein the glycosaminoglycan nanostructure Gt;
delete The method according to claim 1,
Wherein the drying step comprises drying the secondary cooling product by a sublimation reaction using a vacuum pump.
delete The method according to claim 1,
Wherein the drying step raises the temperature at a rate of 5-10 DEG C / hr.
The mixture of glycosaminoglycan and the sugar alcohol is gradually cooled from -10 ° C to -10 ° C at a rate of 1 to 2 ° C / hr starting from 10 ° C to 30 ° C, cooled to 2 to 2.5 ° C / hr After cooling from -12 DEG C to -14 DEG C, it is further cooled at a rate of 2.5 to 3 DEG C / hr from -45 DEG C to -55 DEG C, and then cooled to 10 DEG C to 30 DEG C by 0.5 DEG C Wherein the glycosaminoglycan nanostructure is dried by raising the temperature to the stepwise temperature of the time interval.
15. A formulation comprising the nanostructure of claim 15 and an active ingredient.

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