KR101644154B1 - Water soluble caffeine, preparing method thereof using the same - Google Patents

Abstract

The present invention relates to water soluble caffeine, a manufacturing method thereof, and a processed product comprising the water soluble caffeine as a main material. More particularly, the water soluble caffeine has improved thermal stability and skin permeability at low temperatures, and increases the amount of caffeine dissolved in water by using a principle of molecular complexes between caffeine and a cyclic low-molecular substance having a molecular structure similar to a water soluble low-molecular substance and caffeine. The water soluble low-molecular substance and the cyclic low-molecular substance form a physical bonding with caffeine, and the physical bonding may be one of pi-pi stacking, a hydrophobic interaction, and all physical bonds formed between molecules.

Description

Water soluble caffeine and preparing method thereof [

More particularly, the present invention relates to a water-soluble caffeine and a method for preparing the same, and more particularly, to a water-soluble caffeine and a method for preparing the same, The present invention relates to a water-soluble caffeine prepared by using the principle and a process for producing the same.

The skin at the outermost part of the human body is the most important organ that plays an important role in protecting the bones and organs of the human body from the external environment and maintaining the body temperature and preventing the water loss in the body. Such skin is a very complicated organ, but it can be classified into four layers of stratum corneum, epidermal layer, dermal layer and subcutaneous fat layer, and each layer plays a different role.

For example, the stratum corneum is a collection of dead cells formed after the keratinocytes formed in the keratinocytes at the bottom of the epidermis layer rise up after a certain period of lifting of the nucleus, and a keratinocyte is a hydrophobic substance called ceramide It forms a chemical covalent bond and is tightly formed. It ultimately prevents evaporation of water from the epidermis and dermis layers, and acts as a primary barrier to prevent external pathogens.

The skin layer below the stratum corneum consists of a stratum lucidum, a stratum granulosum, a stratum spinosum and a stratum germinativum. The basal layer contains keratinocyte: about 80% of epidermal cells ) And melanocyte (Melanocyte: about 5% of epidermal cells) are located, which plays an important role in the stratum corneum assistant which plays a role of human skin color, moisture evaporation and immunity.

The dermis layer below the epidermis has the largest area of the four skin layers, with hyaluronic acid, a natural moisturizing factor, and skin elasticity factors such as collagen and elastin. In addition, capillary vessels that supply nutrients in the body are connected to the dermis layer, thus providing nutrients to the skin.

The subcutaneous fat layer is located in the innermost part of the skin. Most of the fat is composed of fat. It protects the internal organs by mitigating the external impact and helps to maintain the body temperature by blocking heat. However, obesity occurs when these fat cells become uneven or excessively increased in number.

On the other hand, obesity is the accumulation of energy in the form of body fat in the body when energy consumption is low compared to the nutrients consumed. Obese people are twice as likely to die as normal people, and they are also more likely to develop hypertension, diabetes, hyperlipidemia, obesity, obstructive sleep, sleep apnea, depression, degenerative arthritis and gout.

Adipocytes increase in number of cells before adolescence, and as the adolescence increases, the number of cells does not increase any more, but the size of the cells grows larger. Thus, childhood obesity increases the likelihood of obesity even if it becomes an adult.

Cellulite is a mixture of waste and moisture accumulated in the body and fat, which makes the surface of the skin bumpy, bouncy, and colder than other areas. Although it differs from obesity caused by fat accumulation of adipocytes or proliferation of adipocytes, it is primarily caused by excessive fat cells.

Conventionally known methods of improving obesity include a method of adjusting the amount of food and nutrient composition. However, simply reducing the amount of food or fasting can have adverse health effects.

The second is to increase the amount of energy consumed rather than the amount of nutrients consumed to prevent fat from accumulating in the body and to burn fat to decompose fat.

The third is drug-induced. It is a way to prevent excess energy from being synthesized into fat or to prevent the accumulation of synthetic fat in the body, or to break down fat cells to help reduce body fat.

The fourth method is to use liposomal (for slimming) cosmetics. It is a method of massaging with cosmetics containing ingredients of fat decomposition and appropriate stimulation.

Finally, there are methods of gastrectomy and gastric banding as medical therapy. It is primarily a measure of hyperbaric obesity and is a way to help reduce weight by forcibly reducing intake.

In addition to caffeine, which blocks ultraviolet rays in the stratum corneum and skin layer of skin, it inhibits the induction of various dermatitis. It is also reported that caffeine inhibits aggregation of adipocytes when reaching the subcutaneous fat layer, thereby inhibiting obesity.

However, the water solubility of caffeine is extremely limited (1%), and even when forming a molecular complex with other water-soluble small molecules, the number of water molecules per unit volume increases at low temperatures below 4'c, This is because the hydrophilic group group which is in contact with caffeine becomes stronger and the water-soluble caffeine molecular complex does not maintain its form and precipitates crystals. Thus, its use in cosmetics and pharmaceutical formulations is very limited, This was difficult.

Accordingly, caffeine, which is used as conventional cosmetics and pharmaceuticals, has poor stability in water and temperature during the prescription, especially in a low temperature environment, so that the crystals are formed in the form of needles, And the use of such materials has been limited.

In particular, the efficacy and efficacy are not clear when used in small quantities, and thus, side effects such as skin irritation caused by excessive use of surfactant or organic solvent (ethanol) have been frequently reported.

In addition, when an excessive amount of surfactant and organic solvent are used, there is a problem in penetration of the skin due to an increase in particle size, so it is difficult to expect sufficient efficacy and effect.

Further, even if a large amount of caffeine is dissolved by specific methods, there is a problem that it is difficult to use due to the formation of needle-shaped crystals according to the temperature change.

German patent DE2422874 Korean Patent Publication No. 10-2013-0109282

Disclosure of Invention Technical Problem [8] The present invention has been made in view of the above problems, and it is an object of the present invention to provide a caffeine composition which can dramatically increase the water solubility of caffeine without using an excessive amount of surfactant or organic solvent, The present invention also provides a water-soluble caffeine, a process for producing the caffeine, and a processed product.

According to an aspect of the present invention, there is provided a molecular complex comprising a water-soluble low-molecular substance and a ring-like low-molecular substance having a molecular structure similar to that of caffeine physically bound to caffeine, wherein the water-soluble low-molecular substance and the cyclic low- The resulting physical binding provides water-soluble caffeine characterized by being one of II-II stacking, hydrophobic interaction, and all physical bonding occurring between molecules.

According to a preferred aspect of the present invention, the water-soluble low molecular weight material is selected from the group consisting of N, N-diethylnicotinamide, Nmethylnicotinamide, N-picolylnicotinamide, N-allylnicotinamide, 2-hydroxy-N, N-diethylnicotinamide, 3-picolylamide, But are not limited to, resorcinol, sodium salicylate, 6-hydroxy-N, N-diethylnicotinamide, betaine, pyrogallol, , Phloroglucinol, nicotinamide, and nicotinic acid. [0030] The term " pharmaceutically acceptable carrier "

According to a preferred aspect of the present invention, the cyclic low molecular weight material may be at least one selected from the group consisting of Xanthine, Theobromine, Theophylline and Paraxanthine.

According to a preferred aspect of the present invention, the ratio of the caffeine: the water soluble low molecular substance: the cyclic low molecular substance may be 4: 6: 3 to 5: 0.5 to 2.

According to another aspect of the present invention, there is provided a method for preparing water-soluble caffeine comprising the steps of adding a cyclic low molecular weight substance having caffeine, a water-soluble low molecular weight substance and caffeine similar in molecular structure to water and stirring to prepare a water- Wherein the water soluble low molecular weight material is selected from the group consisting of N, N-diethylnicotinamide, Nmethylnicotinamide, N-picolylnicotinamide, N-allylic nicotinamide, N-allylnicotinamide, 2-hydroxy-N, N-diethylnicotinamide, 3-picolylamide, resorcinol, Sodium salicylate, 6-hydroxy-N, N-diethylnicotinamide, betaine, pyrogallol, phloroglucinol phloroglucinol, nicotinamide e) and nicotinic acid, and the cyclic low molecular weight material is at least one selected from the group consisting of Xanthine, Theobromine, Theophylline and Paraxanthine Soluble caffeine is at least one selected from the group consisting of water-soluble caffeine.

In addition, the method for producing water-soluble caffeine of the present invention may further comprise lyophilizing the mixed aqueous solution to obtain water-soluble caffeine in powder form.

According to a preferred feature of the present invention, in the step of preparing the mixed aqueous solution, the stirring speed may be 2,000 rpm or more.

Further, the present invention provides a processed product containing the water-soluble caffeine as a main ingredient.

According to one embodiment of the present invention, the water solubility is increased compared to conventional water-soluble caffeine and stable at a temperature (especially at low temperature), so that the product is not decomposed or crystallized in the form of preparation and storage, There is an effect that can be manufactured.

In the present invention, Xanthine, Theobromine, Theophylline, and Paraxanthine, which are similar in molecular structure to caffeine but higher in water solubility than caffeine, ), There is an effect that the stability against temperature is improved so that the water-soluble caffeine molecular complex is not precipitated even at a low temperature.

In addition, according to one embodiment of the present invention, caffeine, which is low in solubility in water and low in stability against temperature, is not easily used in pharmaceuticals including cosmetics, and dissolves in water without use of an emulsifier (surfactant) It can be used as a water soluble caffeine which can increase water solubility dramatically, increase the stability to temperature, and reduce the irritation of the skin while making it easier to penetrate the skin. It is possible to apply the present invention to various processed products such as cosmetics and medicines.

1 is a graph showing the results of solubility test of caffeine according to the weight percentage of the water-soluble low molecular weight substance.
2 is a graph showing the skin permeability test results according to the weight% of the water-soluble low-molecular substance.
3 is a graph showing the results of solubility test of caffeine according to the weight percentage of the caffeine-like cyclic low-molecular substance.
4 is a graph showing the results of skin permeability test according to the weight percentage of the caffeine-like cyclic low-molecular substance.
FIG. 5 is a photograph showing changes in water-soluble caffeine and water-soluble caffeine according to an embodiment of the present invention after storage at low temperature for 4 weeks.
6 is an exploded perspective view schematically showing a Franz cell used in the preparation of aqueous caffeine.
FIG. 7 is a bar graph showing the skin penetration test results of conventional aqueous liquid pure caffeine, conventional water-soluble caffeine, and water-soluble caffeine according to an embodiment of the present invention, respectively.

Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings.

However, the embodiments of the present invention can be modified into various other forms, and the scope of the present invention is not limited to the following embodiments.

In addition, to include an element throughout the specification does not exclude other elements unless specifically stated otherwise, but may include other elements.

Caffeine is a substance found in the leaves and seeds of plants and is a natural substance in white powder form with insecticidal, UV-blocking and lipolytic functions.

Such caffeine is used as a natural sunscreen, whitening agent, and lipid releasing agent in the cosmetics industry, but because of its physical properties that are insoluble in water, it is difficult to apply it as a cosmetic formulation.

The water-soluble caffeine of the present invention is produced by physically combining a water-soluble low-molecular substance and a cyclic low-molecular substance having a molecular structure similar to that of caffeine, with caffeine. Here, the low molecular weight means 500 Da (molecular weight unit Da: daltone) or less.

The structural formula of caffeine of the present invention is shown in the following chemical formula 1.

Here, "water-soluble caffeine" is collectively referred to as caffeine prepared to be easily dissolved in water. The reason that caffeine is solubilized in aqueous solution is that the physicochemical properties are changed from egg / insoluble to water-soluble by theoretically forming a new molecular complex by physically bonding water-soluble low-molecular substance and caffeine with caffeine it means.

The water-soluble low-molecular substances used in the water-soluble caffeine of this embodiment are used for various purposes in pharmaceuticals, cosmetics, beverages and foods, and improve the solubility of caffeine in binding to caffeine in an aqueous solution.

The water-soluble low molecular weight material may be at least one selected from the group consisting of N, N-diethylnicotinamide, Nmethylnicotinamide, N-picolylnicotinamide, N-allylnicotinamide, N-allylnicotinamide, 2-hydroxy-N, N-diethylnicotinamide, 3-picolylamide, resorcinol, Sodium salicylate, 6-hydroxy-N, N-diethylnicotinamide, betaine, pyrogallol, phloroglucinol, ), Nicotinamide, and nicotinic acid. ≪ Desc / Clms Page number 7 >

The structural formula of the water-soluble low-molecular substance is shown in the following chemical formula 2.

In addition, low molecular weight substances with similar caffeine and molecular structure have a high similarity to caffeine, which greatly improves the stability of caffeine.

Conventionally, water-soluble caffeine is used to reduce the surface tension of the hydrophobic part of caffeine by using a surfactant or to temporarily increase the solubility of caffeine by using an organic solvent such as ethanol in an aqueous solution. When a surfactant is used, It is difficult to dissolve ethanol. Or less at a low temperature, resulting in a problem in the application of cosmetic formulations.

However, the cyclic low-molecular substance contained in the water-soluble caffeine of the present embodiment forms a synergistic bonding force with a water-soluble low molecular substance, thereby acting as a triple molecular complex to alleviate skin irritation and enhance penetration of the skin compared to existing surfactants or organic solvents do.

The cyclic low-molecular substance having a molecular structure similar to that of caffeine may be at least one substance selected from the group consisting of Xanthine, Theobromine, Theophylline and Paraxanthine.

The structural formula of the cyclic low-molecular material is shown in the following chemical formula 3.

The mechanism for the formation of molecular complexes in water-soluble caffeine of the present invention is as follows.

The water-soluble low molecular weight material is used as a first solubilizing agent and has a structural characteristic such as a hydroxy group, an amide group, and a carboxy group. Here, the hydroxy functional group means? H functional group, the amide functional group means ONH functional group, and the carboxy functional group means -COOH.

Such a first solubilizing agent is one in which physical bonding is generated by pi-pie stacking (force by electrostatic friction of a hydrophobic group) and hydrophobic interaction of an aromatic group of a water-soluble low molecular substance with a hydrophobic group of caffeine, Physical bonding is created by the pi-pie stacking (the force by the electrostatic friction of the hydrophobic group) and the hydrophobic interaction between the aliphatic group of low molecular substances and the double bond of caffeine.

Particularly, the hexagonal structure and the pentagonal structure of the cyclic low-molecular substance having a molecular structure similar to that of the caffeine used as the second solubilizing agent can be obtained through the pi-pi stacking and hydrophobic interaction with the left and right double bonds of the hexagonal structure and the pentagonal structure of caffeine To form a complex.

That is, in the molecular complex of the present embodiment, the molecular complex of the water soluble low molecule and the caffeine has a physical bond (II) between the hexagonal structure of the water soluble low molecule and the ring part of the caffeine, (II-II-stacking), and the molecular complexes of caffeine and caffeine, which are similar in molecular structure to caffeine, are physically bonded (II-II-II stacking) throughout the hexagonal structure of the ring- .

The physical binding (II-II stacking) formed has the effect of cyclic low molecular weight molecules similar in molecular structure to caffeine, which forms a physical bond (II-II stacking) over the caffeine molecules rather than the cyclic / It receives a lot.

The structural formula of the molecular complex is as follows. (4) includes a cyclic water-soluble low molecular weight material, and (5) includes a non-cyclic water-soluble low molecular weight material.

The molecular complexes thus formed enable the caffeine aggregated macromolecules to exist as single molecules of caffeine, where the molecular complexes have a higher proportion of hydrophilic groups in the molecule than caffeine single molecules, thereby increasing the acceptability of caffeine.

This is because the ring-type low molecular weight substance having similar molecular structure to caffeine has a structure similar to that of caffeine, but has a relatively high water solubility due to a high proportion of the hydrophilic group in the molecule than caffeine.

Therefore, water-soluble caffeine prepared by adding a cyclic low-molecular substance having a similar molecular structure to caffeine can solubilize a large amount of caffeine.

At this time, the second solubilizing agent has a large bonding area with caffeine, which improves the stability of the finished water-soluble caffeine because the water-soluble low molecular substance binds to one of the aromatic group or aliphatic group of caffeine, Similar cyclic low molecular weight substances have a significant influence on the stability of water soluble caffeine because they bind to all the hydrophobic groups throughout the aromatic and aliphatic groups of caffeine.

In addition, a water-soluble low-molecular substance and a ring-type low-molecular substance having a molecular structure similar to that of caffeine wrap the caffeine molecule in the front, back, upper and lower three-dimensional multi-faces, thereby reducing the surface area of the caffeine molecule itself in contact with water, By breaking the bond, the caffeine molecule reduces the specific surface area of contact with water, thus enabling the production of higher contents of water-soluble caffeine.

Furthermore, complex solubilizing agents composed of water-soluble low-molecular substances and cyclic low-molecular substances having molecular structure similar to caffeine have the effect of generating molecular-weight amphoteric substances due to the combination of hydrophilic low molecular weight and low molecular weight substances similar to caffeine, .

In the preparation of the water-soluble caffeine of this embodiment, the weight percentage ratio of the caffeine to the water-soluble low molecular weight substance to the low molecular weight substance having a molecular structure similar to that of caffeine may be 4 to 6: 3 to 5: 0.5 to 2, 5: 4: 1. At this time, the weight percentage ratio can be varied flexibly depending on the controlled content of each material group.

FIG. 1 is a graph showing the results of the dissolution test of caffeine according to the weight% of the water-soluble low molecular weight substance, and FIG. 2 is a graph showing the skin permeation rate test results according to weight% of the water-soluble low molecular weight substance. Here, the weight% ratio of the cyclic low molecular weight substance similar to caffeine was fixed to 1% of the content of the water soluble low molecular weight substance.

1 and 2, when the weight percentage of the caffeine to the water-soluble low molecular weight substance is less than 3 in the preparation of the water-soluble caffeine of the present invention, there arises a problem that the caffeine is not sufficiently dissolved, If the ratio is more than 5, the size of the formed molecular complex becomes excessively large, which causes problems in skin permeation.

FIG. 3 is a graph showing the results of solubility test of caffeine according to the weight percentage of the caffeine-like cyclic low molecular weight substance, and FIG. 4 is a graph showing the skin penetration test results according to the weight percentage of the caffeine-like cyclic low molecular weight substance. Here, the weight percentage of the water-soluble low-molecular substance was fixed to 4% of the content of the low molecular weight substance having a molecular structure similar to that of caffeine.

3 and 4, when the water-soluble caffeine of the present invention has a weight percentage of less than 0.5% by weight of the cyclic low molecular weight substance having a molecular structure similar to that of caffeine to caffeine, sufficient dissolution of caffeine is not achieved, And when the weight percentage ratio of the cyclic low-molecular weight substance having a molecular structure similar to that of caffeine to caffeine exceeds 2, the size of the formed molecular complex becomes excessively large, which causes problems in skin permeation.

In the meantime, when the weight percentage of the water-soluble low molecular weight substance is 4 or less, stability can be secured in a low temperature storage state in an aqueous solution by controlling the weight percentage of the low molecular weight substance having a molecular structure similar to that of caffeine.

The water-soluble caffeine of the present invention can be prepared into any formulation conventionally produced in the art. For example, be formulated into a processed product such as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion, foundation, wax foundation or spray But the present invention is not limited thereto.

The present invention may be more particularly made of processed products such as softeners, nutritional lotion, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder formulations.

Hereinafter, a method for producing the water-soluble caffeine of the present invention will be described.

A method for producing water-soluble caffeine according to an embodiment of the present invention is to add an aqueous solution of a coke-like low-molecular substance having caffeine, a water-soluble low-molecular substance and caffeine similar in molecular structure to water and stirring to obtain an aqueous mixture sufficiently formed by physical bonding.

At this time, it is preferable that the high-water-soluble low-molecular substance, which is a solubilizing agent, and the cyclic low-molecular substance having a molecular structure similar to that of caffeine are stirred at a high speed in order to increase the number of intermolecular collisions with caffeine in an aqueous solution. Further, when the mixture is well mixed through the high-speed stirring, a smaller and even-sized particle can be formed. For example, in order to produce a water-soluble caffeine which is stable even at a low temperature, the stirring speed is preferably 2,000 or less rpm or more. The stirring time is not particularly limited, but preferably about 30 minutes.

When 20% caffeine aqueous solution is prepared, a mixture of 50% by weight of caffeine, 50% by weight of cyclic / non-cyclic water-soluble 40% by weight of a low-molecular substance and 10% by weight of a cyclic low-molecular substance having a molecular structure similar to that of caffeine.

Next, the aqueous solution mixture in a completely mixed state with high-speed stirring can be lyophilized while maintaining its state as necessary to obtain water-soluble aqueous caffeine.

The water-soluble caffeine powder obtained by lyophilizing the water-soluble mixture has advantages such as ease of product production, storage of raw materials, and high production efficiency than liquid water-soluble caffeine. However, since it is difficult to bind the first and second solubilizing agents and caffeine in a powder state, it is necessary to prepare the aqueous solution mixture as the liquid water-soluble caffeine.

Hereinafter, the present invention will be described in more detail with reference to Production Examples and Experimental Examples.

It is to be understood, however, that these Examples and Experimental Examples are for the purpose of describing the present invention only more specifically, and that the scope of the present invention is not limited by these Preparation Examples and Experimental Examples according to the gist of the present invention. Will be apparent to those of ordinary skill in the art.

≪ Preparation Example: Preparation of water-soluble caffeine >

Soluble caffeine for cosmetic and pharmaceutical use is prepared according to the ingredients and the content (unit: wt%) shown in Table 1 below.

In Examples 1 to 8, a water-soluble low-molecular substance as a first solubilizing agent and a cyclic low-molecular substance having a molecular structure similar to that of caffeine as a second solubilizing agent are added and stirred at room temperature for 30 minutes to obtain water-soluble caffeine. In Comparative Examples 1 to 14, caffeine was stirred at a high temperature for 30 minutes with water-soluble low-molecular substances to obtain water-soluble caffeine. In Comparative Examples 15 to 19, caffeine was stirred with a surfactant or an organic solvent (ethanol) at room temperature for 30 minutes to prepare water-soluble caffeine.

<Experimental Example 1: Measurement of Stability by Temperature>

The saturated solutions of each of the examples and comparative examples prepared in the Production Example were stored at room temperature and low temperature (2 占 폚, 4 占 폚) for 4 weeks, and the presence or absence of precipitates was visually observed. The results are shown in the following Table 2, do.

Referring to Table 2, in the case of Examples 1 to 8, precipitates were not generated at room temperature and 4'c or lower. On the other hand, in the case of Comparative Examples 1 to 19, a precipitate was generated at room temperature and at a low temperature of 4'c or 2'c. Therefore, it can be confirmed that when the cyclic low-molecular substance having a molecular structure similar to that of caffeine as the present invention is added, the temperature stability is excellent.

FIG. 5 is a photograph showing changes in water-soluble caffeine and water-soluble caffeine according to an embodiment of the present invention after storage at low temperature for 4 weeks. Each sample is produced at the production ratio shown in Table 3 below.

&Lt; Production rate of water-soluble caffeine sample >

The production ratio used in this experiment was based on a weight ratio of 100%. This experiment was carried out with the change of temperature at low temperature of 2'c ~ 4'c. This is because the same temperature is not applied when storing water-soluble caffeine product and instantaneous change is similar to actual situation to be.

Sample A was obtained by converting the median of the caffeine and nicotinamide content ratios described in the German invention patent DE2422874 into a weight ratio. Samples B and C were prepared so that the content ratio of the substances other than caffeine was equal to 30, and in Experiment B, the content ratio of 30 was used as a water-soluble low-molecular substance as disclosed in the prior art publication No. 10-2013-0109282, Sample C was obtained in accordance with the present example using water-soluble low-molecular substance 20 and substance 10 similar in molecular structure to caffeine.

Referring to FIG. 5, as a result of the experiment for preparing 5% of caffeine aqueous solution, Sample A contained all the caffeine precipitates to form a cloud layer, and Sample B precipitated some caffeine, resulting in precipitates at the bottom of the mixture. It can be seen that Sample C, which is an embodiment of the present invention, solves the stability problem at low temperature of water-soluble caffeine because no precipitate is generated. 94. It is considered that the cyclic low molecular weight substance having similar molecular structure to caffeine contributes to the stability of the caffeine mixture when producing water-soluble caffeine.

Experimental Example 2: Comparison of skin permeability of water-soluble caffeine [

The skin permeability of the water-soluble caffeine obtained in Examples 1 to 8 and Comparative Examples 1 to 19 was measured using a whole skin (including the skin layer and the dermal layer) of Franz Cel l and the cadaver.

First, the water-soluble caffeinated saturated aqueous solutions prepared in Examples 1 to 8 and Comparative Examples 1 to 19 are all diluted with an aqueous 1% solution.

Next, the diluted 27 caffeine aqueous solutions were each titrated with 2 g of the caffeine skin in an Franz cell with an electronic pipette, and then left at room temperature and 1 atm for about 3 hours. The structure of the used Franz cell is shown in FIG.

Next, after 3 hours, the caffeine aqueous solution permeated from the sampling port was extracted and quantitatively measured using a high performance liquid column (HPLC). The results are shown in FIG.

Figure 7 shows the results of a 1% (pure) caffeine aqueous solution (Comparative Example 15-19), 1% of conventional water soluble caffeine by applying the whole skin (cadaver skin containing the horny layer, epidermal layer and dermal layer) to Franz Cell, (Comparative Example 1-14) and 1% of water-soluble caffeine of the present invention (Examples 1-8) obtained by applying the principle of molecular complexes

Referring to FIG. 7, the conventional aqueous liquid caffeine has a skin permeability of 5'c or less and a skin permeability of about 10 to 20'c in the case of conventional water-soluble caffeine in which only water-soluble low-molecular substances are added alone. It can be confirmed that the water-soluble caffeine of the present invention including the cyclic low-molecular substance is superior to the comparative examples in skin permeability of about 25 to 30'c.

Trita. The water permeable caffeine according to the present invention (Examples 1 to 8) is superior to the water soluble caffeine (Comparative Examples 1 to 19) prepared using a surfactant or an organic solvent (ethanol) by using the principle of a triple molecular complex It can be confirmed that it is remarkably high.

This means that the molecular size of the water-soluble caffeine is smaller than the size of the water-soluble caffeine dissolved using a general surfactant or an organic solvent while forming a molecular complex in the solubilization step, and at the same time, the well- It means together.

Accordingly, the water-soluble low-molecular substance of the present embodiment and the low molecular weight substance having a molecular structure similar to that of the caffeine are added together to form a molecular complex, and thus the water-soluble caffeine has a higher skin permeability than pure caffeine or conventional water- It can be seen that the physiological activity is better when used.

The present invention is not limited by the above-described embodiment and the accompanying drawings, but is intended to be limited by the appended claims.

It will be apparent to those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. something to do.

Claims (8)

A water-soluble low-molecular substance and a cyclic low-molecular substance having a molecular structure similar to that of caffeine physically bind to caffeine to form a molecular complex,
The physical interactions of the water-soluble low-molecular substance and the cyclic low-molecular substance with the caffeine are a II-II stacking or hydrophobic interaction,
The water-soluble low-
N-diethylnicotinamide, N-methylnicotinamide, N-picolylnicotinamide, N-allylnicotinamide, 2 3-picolylamide, resorcinol, sodium salicylate, 6-hydroxy-N, N-diethylnicotinamide, (6-hydroxy-N, N-diethylnicotinamide), betaine, pyrogallol, phloroglucinol, nicotinamide, And at least one selected from the group consisting of nicotinic acid
The cyclic low-
Wherein the water soluble caffeine is at least one selected from the group consisting of xanthine, theobromine, theophylline and paraxanthine. delete delete The water-soluble caffeine according to claim 1, wherein the ratio of the caffeine: the water soluble low molecular substance: the cyclic low molecular substance is 4: 6: 3 to 5: 0.5 to 2. In the method for producing water-soluble caffeine,
A step of adding a cyclic low-molecular substance having caffeine, a water-soluble low-molecular substance and caffeine having a similar molecular structure to water, and stirring to prepare a mixed aqueous solution having physical bonds,
The water-soluble low-molecular substance may be at least one selected from the group consisting of N, N-diethylnicotinamide, Nmethylnicotinamide, N-picolylnicotinamide, N-allylic nicotinamide, N-allylnicotinamide, 2-hydroxy-N, N-diethylnicotinamide, 3-picolylamide, resorcinol, sodium salicylate sodium salicylate, 6-hydroxy-N, N-diethylnicotinamide, betaine, pyrogallol, phloroglucinol, At least one selected from the group consisting of nicotinamide, nicotinamide and nicotinic acid,
Wherein the cyclic low molecular weight material is at least one selected from the group consisting of Xanthine, Theobromine, Theophylline and Paraxanthine. 6. The method of claim 5, wherein the mixed aqueous solution is lyophilized to obtain a water soluble caffeine in powder form; &Lt; / RTI &gt; further comprising the step of: The method for producing water-soluble caffeine according to claim 5, wherein, in the step of preparing the mixed aqueous solution, the stirring speed is 2,000 rpm or more. delete

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