Patent Application
20230042360
The present invention relates to a structure for accelerating transdermal absorption, which can accelerate transdermal absorption of an active ingredient, a method of manufacturing the structure for accelerating transdermal absorption, and a cosmetic composition comprising the structure for accelerating transdermal absorption.
In general, scars rarely remain even when skin damage occurs as a child, whereas scars easily remain when skin damage occurs with age, which is predicted to be because the proliferation rate of skin keratinocyte stem cells and transit-amplifying cells required for skin regeneration is remarkably lowered by skin aging. That is, as the skin aging progresses, the proliferation rate of various cells decreases, thereby resulting in a decrease in skin regeneration ability, the wrinkle formation, the blemish formation, a reduction in skin elasticity, and the like.
Accordingly, techniques for various skin care methods or cosmetic compositions for preventing skin aging or maintaining or improving the current level of skin condition have been proposed.
Specifically, Korean Patent Laid-open No. 2010-0104703 relates to a functional cosmetic composition for renewing skin and a method for using the same, and discloses that it is possible to facilitate the transdermal absorption, lower the cytotoxicity, and have the skin regeneration effect by using 5-aminolevulinic acid ester or a salt thereof as an active ingredient. In addition, Korean Patent Laid-open No. 2011-0119062 relates to an enriched media of human adipose tissue-derived stem cells and uses thereof, and discloses that it is possible to have skin regeneration or wrinkle improvement effect by using an enriched media of human adipose tissue-derived stem cells as an active ingredient. In addition, Korean Patent Laid-open No. 2018-0134468 relates to cosmetic compositions comprising spicule, marine collagen and deep ocean water, and their preparation, and discloses that it is possible to obtain wrinkle improvement, pigmentation alleviation, acne improvement, or new skin regeneration effect by using deep ocean water and marine collagen extract rich in various minerals.
However, the above techniques have a problem that the effect of preventing skin aging or maintaining and improving the skin condition is not large because the transdermal absorption rate of the active ingredient is low and there is a limit to the deep penetration of the active ingredient into the skin.
It is an object of the present invention to provide a structure for accelerating transdermal absorption, which can increase the transdermal absorption rate of an active ingredient and deeply penetrate an active ingredient into the skin.
It is another object of the present invention to provide a method of manufacturing the structure for accelerating transdermal absorption.
It is still another object of the present invention to provide a cosmetic composition comprising the structure for accelerating transdermal absorption.
To solve the above problems, the present invention provides a structure for accelerating transdermal absorption, comprising: an acicular body; a hydrophilic group binded to the acicular body; and a carrier binded to the hydrophilic group.
In addition, the present invention provides a method of manufacturing a structure for accelerating transdermal absorption, comprising the steps of: washing an acicular body; reacting the washed acicular body with a basic compound to bind a hydrophilic group to the acicular body; and mixing a carrier and the acicular body to which the hydrophilic group is binded, thereby binding the carrier to the hydrophilic group.
In addition, the present invention provides a cosmetic composition comprising: the structure for accelerating transdermal absorption; and an active ingredient contained in the structure for accelerating transdermal absorption, wherein the active ingredient is one or more selected from the group consisting of nicotinamide adenine dinucleotide (NAD+), nicotinamide mononucleotide (NMN), nicotinamide (NAM), nicotinamide riboside (NR), retinol, retinyl acetate, retinyl palmitate, acetyl hexapeptide-3 (Ac-EEMQRR-NH2), pentapeptide-3 (GPRPA-NH2), pentapeptide-18 (Y(dA)GFL-NH2), palmitoyl tripeptide-1 (pal-GHK-NH2), palmitoyl pentapeptide-4 (pal-KTTKS-NH2), and hexapeptide-11 (FVAPFP-NH2).
The structure for accelerating transdermal absorption of the present invention may be stably binded to a large amount of carriers as its surface comprises an acicular body modified with hydrophilicity. Therefore, when the structure for accelerating transdermal absorption of the present invention obtained by binding a carrier containing an active ingredient to an acicular body is used in a cosmetic composition, it is possible to provide a cosmetic composition having an excellent functionality (for example, anti-aging function) since the transdermal absorption rate of the active ingredient can be increased and the active ingredient can be deeply penetrated into the skin.
The terms and words as used in the description and claims of the present invention should not be construed as limited to conventional or dictionary meanings, but should be construed as the meaning and concept consistent with the technical idea of the present invention based on the principle that the inventor can appropriately define the concept of the terms to describe its own invention in the best way.
The present invention relates to a structure capable of accelerating skin absorption of an active ingredient in absorbing the active ingredient, which functions to prevent skin aging or to maintain and improve skin condition, to the skin. Specifically, the present invention relates to a structure for accelerating transdermal absorption having both a function of accelerating physical transdermal absorption and a function of accelerating formulation transdermal absorption, which will be described with reference to the drawings as follows:
Referring to
The acicular body 11 included in the structure according to an example of the present invention may have at least a portion having an acicular shape (for example, a needle shape, a cone shape, and a pyramid shape). If the acicular body 11 is dispersed in the skin, it may perform a function of forming a hole in the skin, thereby accelerating physical transdermal absorption of the active ingredient. In addition, since the acicular body 11 may also perform a function of penetrating into the skin to push up and exfoliate the dead skin cells accumulated in the skin, it may also promote the process of skin regeneration.
The material of the acicular body 11 is not particularly limited as long as it is harmless to the human body, but may be a spicule extracted from porifera. As the material of the acicular body 11 is a spicule, it is possible to increase the productivity of the cosmetic composition while minimizing irritation to the skin. In addition, as the spicule is porous, the impregnation of the active ingredient can be efficiently made to increase the functionality of the cosmetic composition.
The hydrophilic group 12 included in the structure according to an example of the present invention is binded to the acicular body 11 (specifically dispersed on and binded to the surface of the acicular body 11), and may perform a function of stably binding the carrier 13 to the acicular body 11.
The hydrophilic group 12 is not particularly limited, but may be a hydroxyl group (—OH). As the hydrophilic group 12 is a hydroxyl group, it is possible to minimize irritation to the skin while increasing the binding force with the carrier 13.
The carrier 13 included in the structure according to an example of the present invention is binded to the hydrophilic group 12, and may contain an active ingredient to perform a function of transporting and delivering the active ingredient into the skin. The carrier 13 may consist of an organic material or an inorganic material. Specifically, the carrier 13 may be an organic material such as a polymer hydrogel, a polymer micelle, a nanoemulsion (size: 100 to 500 nm), a liposome, an oleosome, a niosome, an ethosome, and the like, or an inorganic material such as a talc, a bentonite, a silica, and the like.
The polymer hydrogel may be a material in which a phase transition occurs from a sol to a gel or a gel to a sol. Specifically, the polymer hydrogel may be a material comprising one or more gelling polymers selected from the group consisting of galactomannan, glucomannan, guar gum, locust bean gum, Ceratonia siliqua gum, pluronic, agar, algin, carrageenan, xanthan gum, and gellan gum.
The polymer micelle may be a block copolymer material in which a hydrophilic polymer such as polyalkylene glycol and the like, and a hydrophobic polymer such as polylactide, polyglycolide, polycaprolactone and the like are bonded.
The liposome has a lipid bilayer structure that is structurally similar to the cell membrane or the intercellular lipid of the skin epidermal layer, and may be a material that is hydrophobic inside and hydrophilic outside.
More specifically, the carrier 13 may be a liposome having a hollow therein. The hollow (formed) present inside the liposome may contain an active ingredient to perform a function of delivering the active ingredient into the skin. The liposome may perform a function of delivering the active ingredient to the dermis layer of the skin, thereby accelerating the formulation transdermal absorption of the active ingredient.
The liposome may comprise one or more lipids selected from the group consisting of soybean lecithin (L-α-lecithin), lysolecithin, sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidic acid, phosphatidylethanolamine, dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylglycerol (DMPG), and dipalmitoyl phosphatidic acid (DPPA).
The carrier 13 may be binded to the acicular body 11 with a higher binding force by interconnection with the hydrophilic group 12 of the acicular body 11. The interconnection is not particularly limited, but may be a hydrogen bond or a covalent bond. The carrier 13 may be hydrophilic, and thus increase the transdermal absorption rate of the active ingredient.
Specifically, if the acicular body 11 is porous, the carrier 13 may be binded to the pores of the acicular body 11 through inclusion, and in this case, since the binding force is not high, the carrier 13 may be easily separated from the acicular body 11 during the manufacturing process of the cosmetic composition or the use process of the cosmetic composition. At this time, if the carrier 13 is hydrophilic as in the hydrophilic group 12 binded to the acicular body 11, the carrier 13 may be stably binded to the acicular body 11 by the interaction between the hydrophilic group 12 binded to the acicular body 11 and the carrier 13, and thus the carrier 13 may be prevented from being easily separated from the acicular body 11 during the manufacturing process of the cosmetic composition or the use process of the cosmetic composition. Wherein, if an active ingredient is contained in the carrier 13, the loss of the carrier 13 in the process of transdermal absorption is minimized by stable bond between the acicular body 11 and the carrier 13, thereby increasing the transdermal absorption rate of the active ingredient.
Along with the case where all of the carriers 13 are binded to the hydrophilic group 12 of the acicular body 11, the case where some of the carriers 13 are binded to the hydrophilic group 12 of the acicular body 11 and others of the carriers 13 are binded to the surface of the acicular body 11 to which the hydrophilic group 12 is not binded may be also included in the scope of the present invention.
The structure according to an example of the present invention may have a high porosity so that the inclusion of the carrier 13 is efficiently performed. That is, the structure according to an example of the present invention may have a porosity of 10 to 95%, specifically 20 to 95%, more specifically 30 to 90%, still more specifically 50 to 55%. As the porosity is within the above range, it is possible to maintain the physical strength of the structure while increasing the inclusion rate of the carrier 13. Wherein, the porosity may be a value calculated by the following equation:
Porosity={(W1−W2)/W1}×100 [Equation]
wherein, W1 is the initial weight of the acicular body that is not subjected to the process of pore formation in the manufacturing process of the structure (for example, the weight of the spicules before pore formation); and
W2 is the weight of the acicular body that has been subjected to the process of pore formation in the manufacturing process of the structure (for example, the weight of the spicules after pore formation).
The present invention provides a method for manufacturing the structure as described above and its specific description is as follows:
First, the method of manufacturing the structure according to an example of the present invention comprises the step of washing an acicular body. The washing is for removing impurities present in an acicular body and may be performed using purified water and an acidic solution. Specifically, the washing of an acicular body may be subjected to the process of washing an acicular body with purified water one or more times, and then treating it with an acidic solution such as hydrogen peroxide solution. Wherein, upon treating the acicular body with the acidic solution, ultrasonic waves may be applied. As the ultrasonic waves are applied, the washing efficiency of the acicular body may be increased.
Next, the method of manufacturing the structure according to an example of the present invention comprises the step of reacting the washed acicular body with a basic compound to bind a hydrophilic group to the acicular body. The step is the step of modifying the surface of the acicular body, wherein the basic compound used is not particularly limited, but may be one or more selected from the group consisting of sodium hydroxide, potassium hydroxide, and lithium hydroxide. As the basic compound is the listed compound, the binding efficiency (dispersion efficiency) of the hydrophilic group may be increased. Wherein, the reaction of the acicular body and the basic compound may be performed at 25 to 50° C. for 30 minutes to 2 hours so that the hydrophilic group is well binded to the acicular body.
Next, the method for manufacturing the structure according to an example of the present invention comprises the step of mixing a carrier and the acicular body to which the hydrophilic group is binded, thereby binding the carrier to the hydrophilic group. Wherein, upon mixing the acicular body and the carrier so that the hydrophilic group and the carrier may be well binded, an ultra-high pressure treatment in which a pressure of 50 to 300 MPa is applied for 1 to 10 minutes may be performed.
The method for manufacturing the structure according to an example of the present invention may further comprise the step of forming pores capable of enhancing the porosity of the acicular body. Specifically, prior to reacting the washed acicular body with the basic compound to bind the hydrophilic group to the acicular body, one or more pores are formed in the acicular body by reacting the washed acicular body with an acidic solution (hydrogen peroxide solution). As the process of forming pores is performed, the porosity of the acicular body is enhanced (the number of pores in the acicular body is increased), thereby increasing the inclusion rate of the carrier. Wherein, the reaction between the acicular body and the acidic solution (hydrogen peroxide solution) may be performed at room temperature for 6 to 20 hours. In addition, when the acicular body and the acidic solution (hydrogen peroxide solution) are reacted so that the reaction between the acicular body and the acidic solution (hydrogen peroxide solution) can be activated to efficiently form pores, ultrasonic waves having a frequency of 10 to 70 kHz and an output of 100 to 500 W may be applied.
The process of reacting the acicular body with the acidic solution (hydrogen peroxide solution) to form pores may be repeated one or more times, and applying ultrasonic waves for each process may be selectively performed.
As the structure is manufactured by the manufacturing method as described above, the present invention may provide a structure in which a large amount of carriers are stably binded to the acicular body. Therefore, if the structure of the present invention is used for transdermal absorption of the active ingredient, it is possible to obtain the effect capable of increasing the transdermal absorption rate while accelerating transdermal absorption.
Meanwhile, the present invention provides a cosmetic composition comprising the structure as described above and an active ingredient.
The structure included in the cosmetic composition according to an example of the present invention contains an active ingredient, and its specific description is as described above and thus will be omitted. Wherein, the active ingredient may be contained on the surface of the acicular body included in the structure and/or inside the carrier, and specifically, may be contained inside the carrier.
The content of the structure is not particularly limited, but may be 0.1 to 1 part by weight based on 100 parts by weight of the cosmetic composition.
The active ingredient contained in the structure is not particularly limited, but may be one or more selected from the group consisting of nicotinamide adenine dinucleotide (NAD′), nicotinamide mononucleotide (NMN), nicotinamide (NAM), nicotinamide riboside (NR), retinol, retinyl acetate, retinyl palmitate, acetyl hexapeptide-3 (Ac-EEMQRR-NH2), pentapeptide-3 (GPRPA-NH2), pentapeptide-18 (Y(dA)GFL-NH2), palmitoyl tripeptide-1 (pal-GHK-NH2), palmitoyl pentapeptide-4 (pal-KTTKS-NH2), and hexapeptide-11 (FVAPFP-NH2), which have an excellent anti-aging function.
The content of the active ingredient is not particularly limited, but may be 0.05 to 1 part by weight based on 100 parts by weight of the cosmetic composition.
The cosmetic composition according to an example of the present invention may further comprise purified water, an antioxidant, a stabilizer, a pigment, a perfume, or the like, which is commonly used in field of cosmetic compositions.
In addition, the cosmetic composition according to an example of the present invention may be prepared into a conventional formulation. Specifically, it may be formulated into a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, an emulsion foundation, a wax foundation, a spray, or the like.
Hereinafter, the present invention will be described in more detail by examples. However, the following examples are only for illustrating the present invention, which will be apparent to those skilled in the art that various changes and modifications may be made within the category and spirit of the present invention, and the scope of the present invention is not limited thereto.
1) Washing of Spicule
A spicule (J2KBIO Co., Ltd.) extracted (obtained) from Spongilla lacustris L. was used as an acicular body, and was washed through the following processes: 20 g of spicule was put in 200 ml of purified water to remove salt, and filtered through a 400 mesh polyethylene (PE) filter, and then the spicule left on the filter was washed with purified water two times. Subsequently, the washed spicule was put in a dryer (Hanbaek Co., Ltd.) and dried at 50° C.
To remove impurities remaining in the dried spicule, the dried spicule was put in 200 ml of 35% hydrogen peroxide solution (H2O2) (Samchun Chemical Co. Ltd.) and subjected to ultrasonication under conditions of 300 W and 40 kHz for 1 hour using an ultrasonic cleaner (Sungdong Ultrasonic Co., Ltd.). Then, after filtering it through a 400 mesh polyethylene (PE) filter, the process of washing the spicule left on the filter with 500 ml of purified water was repeated three times. Subsequently, the process of putting the washed spicule into a dryer and drying it at 50° C. was performed to complete the washing of the spicule.
2) Binding of Hydroxyl Group to Spicule
200 ml of 1N NaOH (Sigma-Aldrich Co. Ltd.) was added to 20 g of the pore-formed spicule, and reacted at 40° C. for 1 hour. Then, after filtering it through a 400 mesh polyethylene (PE) filter, the process of washing the spicule left on the filter with 500 ml of purified water was repeated three times. Subsequently, the process of putting the washed spicule into a dryer and drying it at 50° C. was performed to obtain the spicule to which a hydrophilic hydroxyl group was binded.
3) Binding of Liposome to Spicule
0.5 g (5%) of the hydroxyl group-binded spicule and 1 g (10%) of the fluorescent protein liposome as a carrier were added to 8.5 ml of purified water, and the spicule and the fluorescent protein liposome were mixed by stirring at room temperature for 1 hour to prepare a mixed solution containing a spicule-liposome binding structure. At this time, to a solution that was obtained by dispersing 1 g of L-α-lecithin in 6 g of 1,3-butylene glycol (Sigma Co., Ltd.), adding 6 g of purified water, heating it in a hot water bath at 80° C. to dissolve it, and cooling it to 50° C., 1 g of purified water, in which Alexafluor™ 488-binding protein (Thermo Fisher Scientific Co. Ltd.) was dissolved at a concentration of 5 mg/ml, was added in small portions, thereby preparing a mixture, in which these solutions were uniformly mixed with each other, and then 6 g of purified water was added to the mixture in small portions again, stirred at room temperature, and refrigerated at 4° C. to use as the fluorescent protein liposome.
Next, after filtering the prepared mixed solution through a 400 mesh polyethylene (PE) filter, the process of washing the spicule-liposome binding structure left on the filter with 500 ml of purified water was repeated three times. Subsequently, the process of putting the washed spicule-liposome binding structure into a dryer and drying it at 50° C. was performed to obtain a structure, in which the fluorescent protein liposome was binded to the pores of the spicule and the hydroxyl group of the spicule.
A structure was obtained by performing the same process as in Example 1, except that the process of putting the washed spicule into 200 ml of 35% hydrogen peroxide solution (H2O2) (Samchun Chemical Co. Ltd.) and reacting them for 16 hours to form the pores in the spicule was further carried out (the porosity of the spicule is enhanced).
A structure was obtained by performing the same process as in Example 2, except that prior to binding the hydroxyl group to the spicule, the process of putting the pore-formed spicule into 200 ml of 35% hydrogen peroxide solution (H2O2) (Samchun Chemical Co. Ltd.) and being subjected to ultrasonication under conditions of 300 W and 40 kHz for 1 hour using an ultrasonic cleaner was further carried out (addition of one ultrasonication compared to Example 2).
A structure was obtained by performing the same process as in Example 3, except that the process of putting the spicule, which was further subjected to the ultrasonication process, into 200 ml of 35% hydrogen peroxide solution (H2O2) (Samchun Chemical Co. Ltd.) and being subjected to ultrasonication under conditions of 300 W and 40 kHz for 1 hour using an ultrasonic cleaner was carried out again (addition of two ultrasonications compared to Example 2).
A structure was obtained by performing the same process as in Example 2, except that the process of putting 10 g of a mixed solution containing a spicule-liposome binding structure into a plastic pack and vacuum-reducing it, and then pressurizing for 5 minutes at a pressure of 150 MPa using a high-pressure processing machine (Ilshin Autoclave Co., Ltd., Suflux®) was further carried out.
A structure was obtained by performing the same process as in Example 3, except that the process of putting 10 g of a mixed solution containing a spicule-liposome binding structure into a plastic pack and vacuum-reducing it, and then pressurizing for 5 minutes at a pressure of 150 MPa using a high-pressure processing machine (Ilshin Autoclave Co., Ltd., Suflux®) was further carried out.
A structure was obtained by performing the same process as in Example 4, except that the process of putting 10 g of a mixed solution containing a spicule-liposome binding structure into a plastic pack and vacuum-reducing it, and then pressurizing for 5 minutes at a pressure of 150 MPa using a high-pressure processing machine (Ilshin Autoclave Co., Ltd., Suflux®) was further carried out.
A structure was obtained by performing the same process as in Example 1, except that the process of binding a hydroxyl group was not carried out.
A structure was obtained by performing the same process as in Example 2, except that the process of binding a hydroxyl group was not carried out.
A structure was obtained by performing the same process as in Example 3, except that the process of binding a hydroxyl group was not carried out.
A structure was obtained by performing the same process as in Example 4, except that the process of binding a hydroxyl group was not carried out.
The fluorescent protein liposome, which is the carrier used in Example 1, was applied (the fluorescent protein liposome, to which the spicule was not binded, was applied alone).
The conditions of the Examples and Comparative Examples above are summarized as in Table 1 below.
To confirm whether the washing of the spicule was performed well, the spicule before washing and the spicule after washing in Example 1 were checked with an optical microscope (Nikon Corporation, ECLIPSE TS2), and the results are shown in
Referring to
The porosity evaluation for the spicules of Examples 2 to 4, in which washing, pore formation, and/or ultrasonication were performed until the hydroxyl group was binded to the spicule, and the spicule of Comparative Example 1, in which only the washing process was performed, was carried out in the following manner, and the results are shown in
Referring to
Referring to Table 2 above, it can be confirmed that the weight of the spicules in Examples 2 to 4, in which washing, pore formation, and ultrasonication were performed, was significantly reduced compared to Comparative Example 1, in which only the washing process was performed. This can be seen as a result of supporting that as the pore formation and ultrasonication for the spicule are performed as described in the present invention, the porosity of the spicule becomes very high.
To confirm whether the inclusion of the fluorescent protein liposomes was well performed in the structures obtained in Examples 2 to 7 and Comparative Examples 1 to 4, 5 mg of the structure was put into 500 mg of purified water and mixed to prepare a mixed solution, and then 100 mg was taken from the prepared mixed solution, placed on a slide glass, and observed with a fluorescence microscope (NEXCOPE Co., Ltd., NIB410F) GFP filter, and the results are shown in
Referring to
Cosmetic compositions were prepared using the respective structures obtained in Examples 1 to 7. Specifically, based on 100 parts by weight of the cosmetic composition, 2.0 parts by weight of glycerin (moisturizer), 3.0 parts by weight of panthenol (moisturizer), 2.0 parts by weight of Olivem 2020 (emulsifier), and 2.0 parts by weight of hexanediol were put into 72.0 parts by weight of purified water and stirred for 10 minutes at 1,000 rpm to prepare an aqueous phase lysate. Then, to prepare an oily phase lysate, 6.0 parts by weight of caprylic/capric triglyceride (oil), 6.0 parts by weight of cetyl ethylhexanoate (oil), and 1.0 parts by weight of Olivem 1000 (emulsifier) were dissolved while warming to 80° C., and the prepared aqueous phase lysate was put thereinto and stirred at 1,000 rpm to prepare an oily phase lysate. Subsequently, 0.03 parts by weight of an anti-aging peptide, 0.03 parts by weight of nicotinamide riboside, 3.0 parts by weight of butylene glycol, 0.5 parts by weight of soybean lecithin, 0.7 parts by weight of structure (each of Examples 1 to 7), and 0.04 parts by weight of adenosine were further put thereinto and stirred at 60° C. for 5 minutes at 2,000 rpm. Finally, 0.1 parts by weight of perfume, 1 part by weight of Scutellaria baicalensis Georgi extract, 0.5 parts by weight of Portulaca oleracea extract, and 0.1 parts by weight of Jeju cherry blossom extract were put thereinto, and stirred at 50° C. for 5 minutes at 3,000 rpm to prepare cosmetic compositions, respectively.
A cosmetic composition was prepared by performing the same process as in Preparative Example 7, except that the fluorescent protein liposome of Comparative Example 5 was applied instead of the structure of Example 7.
To confirm the degree of skin absorption (penetration) of the cosmetic compositions obtained in Preparative Example 7 and Comparative Preparative Example 1, the tissue section of the pig skin obtained through the process of applying each cosmetic composition to the pig skin (Franz Cell Membrane, FCM, APURES Co., Ltd.) was melted at room temperature, and then a mounting solution (National Diagnostics Corporation) was applied thereto and observed with a fluorescence microscope (Nikon Corporation, ECLIPSE TS2-FL), and the results are shown in
Referring to
To confirm the degree of skin absorption (penetration) of the cosmetic compositions obtained in Preparative Example 7 and Comparative Preparative Example 1, 150 μl of the pig skin sample obtained through the process of applying each cosmetic composition to the pig skin (Franz Cell Membrane, FCM, APURES Co., Ltd.) was placed in a 96-well plate and the skin transmittance was analyzed with a fluorescence spectrophotometer (SpectraMAX M2, Molecular Devices, LLC), and the results are shown in
Referring to
| Number | Date | Country | Kind |
|---|---|---|---|
| 10-2019-0110546 | Sep 2019 | KR | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/KR2020/004966 | 4/13/2020 | WO |
