Clear PVP-fullerene complex

Abstract

PROBLEM TO BE SOLVED: The problem to be solved by the present invention is to elucidate the cause of the turbidity observed in the production of a PVP-fullerene complex aqueous solution and to provide such a composition having high clarity. SOLUTION: It was discovered that a high-clarity composition is obtained by decreasing the residual amount of aromatic hydrocarbons to 3000 ppm or less during drying in a method for producing a PVP-fullerene complex aqueous solution.

Description

Transparent PVP-fullerene composite

[0001] The present invention discloses a complex of fullerenes with improved clarity in aqueous solutions having physiological activities and cosmetic effects such as antioxidant activity, anticancer activity, antibacterial activity, skin whitening and antiwrinkle activity.

[0002] Fullerenes having a C60, C70, or higher carbon spherical shell structure or a tubular structure, including their chemically modified forms, complexes, inclusion complexes, etc., have attracted attention as substances with physiological activities such as antioxidant activity, anticancer activity, and antibacterial activity.

[0003] However, when these fullerenes are actually used, it is not easy to fully exert the physiological activities described above while maintaining stability. In particular, when they are used in a water-soluble form or as a component of an aqueous solution, advanced techniques are required.

[0004] Patent Document 1 discloses that a mixed solution of fullerenes dissolved in an aromatic hydrocarbon and polyvinylpyrrolidone (hereinafter abbreviated as PVP) dissolved in ethanol is evaporated to dryness, water is added to form a suspension, the suspension is evaporated to remove the solvent, and finally water is added to obtain an aqueous solution of a PVP-fullerene complex. Furthermore, Patent Document 2 discloses a method for removing residual solvents by heating the organic solvent used as an extraction solvent for fullerenes at a reduced pressure of 50 Torr or less at a temperature 150°C or higher than the boiling point of the solvent to reduce the residual concentration of the organic solvent to below the limit value specified in the "Guidelines for Residual Solvents in Pharmaceuticals."

[0005] However, although aqueous solutions of PVP-fullerene complexes produced according to these production methods can be used in a water-soluble form or as a component of an aqueous solution, they may lack clarity, and the reason for this has not been clarified. When such suspension samples are used in cosmetics and the like, they impair the appearance and reduce the commercial value, so there has been a demand for improvements in aqueous solutions of PVP-fullerene complexes.

[0006] JP 2005-272639 A JP 2005-306636 A

[0007] The problem to be solved by the present invention is to clarify the cause of turbidity observed in the production of an aqueous solution of a PVP-fullerene complex, and to provide such a composition with high transparency.

[0008] As a result of extensive research into solving the above problems, the present inventors have found that the cause of turbidity in an aqueous solution of a PVP-fullerene complex is the aromatic hydrocarbon in which the fullerene is dissolved, and have further found that a highly transparent composition can be obtained by reducing the amount of the aromatic hydrocarbon remaining after drying to less than 30,000 ppm in a method for producing an aqueous solution of a PVP-fullerene complex.

[0009] That is, the present invention provides: (1) a PVP-fullerene complex or a composition for external use in which the residual amount of aromatic hydrocarbons is less than 30,000 ppm; (2) a PVP-fullerene complex or a composition for external use as set forth in (1) above, in which the aromatic hydrocarbon is toluene; (3) a PVP-fullerene complex aqueous solution or a composition for external use in which the residual amount of aromatic hydrocarbons is less than 3,000 ppm; (4) a PVP-fullerene complex aqueous solution or a composition for external use as set forth in (3) above, in which the aromatic hydrocarbon is toluene; (5) a method for clarifying a PVP-fullerene complex composition containing less than 30,000 ppm of aromatic hydrocarbons, in which the aromatic hydrocarbon is adjusted to less than 30,000 ppm in a PVP-fullerene complex composition containing 30,000 ppm or more of aromatic hydrocarbons; (6) A method for clarifying a PVP-fullerene complex aqueous solution or a topical composition, which contains 3000 ppm or more of aromatic hydrocarbons, by adjusting the aromatic hydrocarbon content to less than 3000 ppm; (7) A method for producing a PVP-fullerene complex composition, which includes a step of evaporating and drying a mixture of fullerenes dissolved in aromatic hydrocarbons and PVP dissolved in ethanol, and which further includes a step of adjusting the aromatic hydrocarbon content in the PVP-fullerene complex composition to 30000 ppm;

[0010] According to the present invention, when the PVP-fullerene complex is used as a component of cosmetics and the like, the amount of residual toluene in the complex can be reduced to 30,000 ppm or less, thereby making it possible to obtain a composition with high transparency when made into an aqueous solution, and the PVP-fullerene complex can be added to cosmetics and the like without affecting their appearance.

[0011] Example 1 PVP-fullerene complex upon evaporation to dryness Example 1 PVP-fullerene complex after evaporation to dryness Example 2 PVP-fullerene complex with different toluene contents

[0012] The present invention will be described in detail below.

[0013] The PVP-fullerene complex aqueous solution in the present invention is an aqueous solution of a complex of fullerene or a fullerene mixture and PVP, and its production method is not limited as long as it does not impair the effects of the present invention, and may be produced, for example, in accordance with the known production method described in Patent Document 1. That is, an aromatic hydrocarbon solution of fullerene or a fullerene mixture (hereinafter also abbreviated as (F·A)) and an ethanol solution of PVP (hereinafter also abbreviated as (PVP·E)) are mixed, and water is added to the mixed solution and the solvent is distilled off to obtain a PVP-fullerene complex aqueous solution.

[0014] The fullerene or fullerene mixture in the present invention includes those having the known C60, C70, or higher carbon shell structures, those having a tube structure such as carbon nanotubes or fullerene tubes, various fullerenes, and mixtures of two or more of these, and hereinafter also referred to as fullerenes. These fullerenes may have structures modified with various substituents as long as the effects of the present invention are not impaired.

[0015] Various aromatic hydrocarbons may be used as a solvent for fullerenes in the present invention as long as they do not impair the effects of the present invention. However, it is preferable to use toluene, xylene, benzene, chlorobenzene, or a mixture of two or more of these aromatic hydrocarbons, and toluene is particularly preferred as a suitable solvent.

[0016] In the present invention, the aromatic hydrocarbon solution of fullerenes (hereinafter also abbreviated as (F·A)) is preferably prepared in a weight ratio (F / A) of fullerenes (F) to aromatic hydrocarbon solvent (A) in the range of 0.0005 to 0.0032, more preferably 0.00075 to 0.00095. If the ratio exceeds 0.0032, it becomes difficult to obtain a homogeneous solution, and it also becomes difficult to obtain a homogeneous solution when the solution is mixed with an ethanol solution of PVP. On the other hand, if the ratio is too small, less than 0.0005, it is not suitable from the standpoint of cost.

[0017] The PVP (polyvinylpyrolidone) used in the present invention may be synthesized or commercially available, as long as it does not impair the effects of the present invention. The weight-average molecular weight (Mw) of the PVP used can be 3,000 to 3,000,000, preferably 6,000 to 1,500,000. It has been known that PVP is poorly soluble in aromatic hydrocarbon solvents (toluene, xylene, benzene, chlorobenzene, etc.) but is soluble in halogenated aliphatic hydrocarbon solvents (chloroform, dichloromethane, 1,2-dichloroethane, etc.). However, since the PVP-fullerene complex aqueous solution of the present invention is intended for use as a raw material for cosmetics and the like, halogenated aliphatic hydrocarbon solvents are not used. Instead, ethanol, which is also a pharmaceutical-acceptable solvent with excellent safety, is used.

[0018] In the present invention, the ethanol solution of PVP (hereinafter also abbreviated as (PVP·E)) is preferably prepared so that the weight ratio of PVP to ethanol (E) (PVP / E) is in the range of 0.01 to 0.5, more preferably 0.125 to 0.25. A weight ratio (PVP / E) of less than 0.01 is undesirable because it requires maintaining extremely high stirring efficiency, while a weight ratio exceeding 0.5 is undesirable because the solution becomes highly viscous, significantly reducing reaction efficiency. Note that in order to obtain a uniform solution (hereinafter also abbreviated as (F·A-PVP·E)) by mixing the ethanol solution of PVP with the aromatic hydrocarbon solution of fullerenes, it is desirable to keep the water content of the solvent ethanol at approximately 0.5% by weight or less.

[0019] In the present invention, the weight ratio of the aromatic hydrocarbon solution of fullerenes (F.A) to the ethanol solution of PVP (PVP.E) (F.A / PVP.E) is preferably in the range of 1.0 to 3.0, more preferably 1.5 to 2.0. A weight ratio of less than 1.0 is undesirable because it reduces the reaction efficiency. On the other hand, a weight ratio of more than 3.0 is undesirable because it makes it difficult to distill off the solvent. There are no particular limitations on the method for mixing the aromatic hydrocarbon solution of fullerenes (F.A) and the ethanol solution of PVP (PVP.E). For example, stirring using a bladed propeller can be used, and the mixture can be performed at a temperature of 15°C to 25°C, at a stirring speed of 400 rpm, for approximately 12 to 15 hours.

[0020] In the present invention, a homogeneous solution (F.A-PVP.E) obtained by mixing an aromatic hydrocarbon solution of fullerenes with an ethanol solution of PVP is converted into an aqueous solution of a PVP-fullerene complex through the steps of adding water and distilling off the solvent.

[0021] In the present invention,

[0022] The method for adding water to the solution (F.A-PVP.E) described in (2) is not particularly limited, and may be carried out in accordance with the method described in Patent Document 1, for example. Specifically, a homogeneous solution (F.A-PVP.E) obtained by mixing an aromatic hydrocarbon solution of fullerenes with an ethanol solution of PVP may be evaporated to dryness, water may be added to form a suspension, and the mixture may be further evaporated to dryness. Finally, water may be added to form an aqueous solution, which serves as the PVP-fullerene complex aqueous solution of the present invention. The amount of water added is preferably adjusted so that the PVP-fullerene complex in the final PVP-fullerene complex aqueous solution is in the range of 5 to 20 wt%, more preferably 6.5 to 14.5 wt%. A concentration of less than 5 wt% results in inefficient evaporation to dryness, while a concentration of more than 20 wt% is undesirable because it increases viscosity and reduces filtration rate.

[0023] The concentration may be adjusted, and the form may be changed depending on the application. Water may be added at the end to form an aqueous solution, or the solution may be evaporated to dryness to form a solid. The temperature of the water to be added is not particularly limited, and it is recommended to prepare the water in the range of about 20°C to 35°C.

[0024] When the PVP-fullerene complex aqueous solution of the present invention is used in pharmaceuticals, it must comply with the "Guidelines for Residual Solvents in Pharmaceuticals" (Ministry of Health, Labor and Welfare, Pharmaceutical and Medical Safety Bureau: March 1998), just like general fullerenes. In other words, aromatic hydrocarbons used as solvents for fullerenes in the production of this aqueous solution are strictly restricted as biologically harmful solvents, and their residual amounts are strictly regulated. The current concentration limits (ppm) in the guidelines are clearly stated as toluene (890 ppm), xylene (2170 ppm), chlorobenzene (600 ppm), hexane (290 ppm), and acetonitrile (410 ppm).

[0025] When the PVP-fullerene complex aqueous solution of the present invention is used in cosmetics, it exhibits colorless and transparent or colored and transparent properties, unlike general fullerenes. In the present invention, colorless and transparent refers to a state in which the PVP-fullerene complex aqueous solution of the present invention transmits light in almost the entire visible range, allowing one to see through the aqueous solution, and visible light is not scattered or absorbed on the surface or inside the aqueous solution. In the present invention, colored and transparent refers to a state in which the PVP-fullerene complex aqueous solution of the present invention transmits part of the visible range, allowing one to see through the aqueous solution, and visible light is partially absorbed on the surface or inside the aqueous solution, but not scattered.

[0026] In the present invention, clarity refers to a colorless, transparent, or colored, transparent state, and the degree of clarity can be easily evaluated by visual sensory evaluation. For example, clarity can be evaluated by holding a colorless, transparent container containing a PVP-fullerene complex aqueous solution over an object such as paper with printed characters and determining whether the characters printed on the object are discernible even through the container. The easier the characters are to distinguish, the higher the clarity is expressed, and the more difficult the characters are to distinguish, the lower the clarity is expressed. Furthermore, in addition to being highly transparent, the PVP-fullerene complex aqueous solution of the present invention does not contain any particles that scatter visible light.

[0027] Generally, when a functional ingredient having physiological activity is used in a cosmetic product, the higher the transparency of the functional ingredient or a composition containing the ingredient, the more versatile and marketable the cosmetic product can be, and the greater its versatility and market value.

[0028] However, there has not been a clear correlation between compliance with the guidelines and high clarity, and ingredients or compositions that satisfy the guidelines do not necessarily have high clarity.

[0029] The toluene concentration contained in the PVP-fullerene complex of the present invention is preferably 3 ppm or more and less than 30,000 ppm, more preferably 3 ppm or more and 20,000 ppm or less, and more preferably 3 ppm or more and 10,000 ppm or less. If the concentration exceeds 30,000 ppm, when dissolved in an aqueous fullerene complex solution or a cosmetic containing the composition, the clarity decreases and turbidity occurs. If the concentration is less than 3 ppm, toluene must be repeatedly distilled off during the production process, which significantly reduces production efficiency.

[0030] The toluene concentration in the PVP-fullerene complex aqueous solution of the present invention or in cosmetics containing the composition is preferably 0.3 ppm or more and less than 3000 ppm, more preferably 0.3 ppm or more and 1000 ppm or less, and more preferably 0.3 ppm or more and 890 ppm or less. If the toluene concentration exceeds 3000 ppm, turbidity is easily observed in the PVP-fullerene complex aqueous solution or in cosmetics containing the composition, while if the toluene concentration is less than 0.3 ppm, the product cost is likely to be high.

[0031] The method for reducing the toluene concentration in the PVP-fullerene complex of the present invention is not particularly limited. For example, in the PVP-fullerene complex production process described in Patent Document 1, the mixing ratio (F.A / PVP.E) of the aromatic hydrocarbon solution (F.A) of fullerene or fullerene mixture to the PVP ethanol solution (PVP.E) may be appropriately adjusted to produce the PVP-fullerene complex with the lowest residual toluene content. Alternatively, the temperature during stirring of the mixture, the rotation speed of the stirrer, and the stirring time may be adjusted to optimize the conditions. Alternatively, the mixture may be repeatedly evaporated to dryness and resuspended by adding water, resulting in an optimal number of cycles. Alternatively, the concentration of the PVP-fullerene complex in the PVP-fullerene complex aqueous solution may be appropriately adjusted to optimize the concentration. Alternatively, the temperature of the water added during this process may be adjusted to optimize the temperature. Alternatively, the residual toluene content may be reduced by performing a heat treatment at a temperature above the boiling point of the solvent under a specific reduced pressure, as described in Patent Document 2.

[0032] The present invention will be specifically described below using examples and comparative examples, but the present invention is not limited to these.

[0033] Example (1) Confirmation of Turbidity in PVP-Fullerene Complex Aqueous Solution To investigate the cause of turbidity in PVP-fullerene complex aqueous solutions, prototypes with different residual amounts of toluene were prepared.

[0034] Example (1) - Test area - Comparison area 1: Toluene remains Test area 1: Toluene has been distilled off

[0035] Example (1) - Materials - Fullerene or fullerene mixture: Powder containing C60 fullerene and C70 fullerene, with an average molecular weight of 744. Toluene: Special grade toluene reagent (manufactured by Wako Pure Chemical Industries, Ltd.) PVP: PVP Plasdone 29 / 32 (M.W. 60,000) Ethanol: Ethanol JP Absolute ethanol (manufactured by Kosakai Pharmaceutical Co., Ltd.)

[0036] Example (1) - Method for preparing PVP-fullerene complex - 1) 16.0 mg of fullerene or fullerene mixture was dissolved in 20 mL of toluene to prepare an aromatic hydrocarbon solution of fullerenes (F.A). 2) 2.0 g of PVP was dissolved in 10 mL of ethanol to prepare an ethanol solution of PVP (PVP.E). 3) (1) F.A and (2) PVP.E were mixed and stirred until homogeneous (room temperature, 12 hours). 4) (3) was evaporated to dryness. There was a difference in the decompression time in operation 4) between comparison area 1 and experimental area 1, and comparison area 1 was treated so that a larger amount of toluene remained than experimental area 1.

[0037] Example (1) - Results - For Comparative Area 1 and Experimental Area 1, the PVP-fullerene complex during evaporation to dryness and the state of the PVP-fullerene complex aqueous solution prepared after evaporation to dryness are shown in Figures 1 and 2. As shown in Figure 1, the PVP-fullerene complex in Comparative Area 1 adhered to the bottom of the eggplant-shaped flask as a cloudy liquid, whereas the PVP-fullerene complex in Experimental Area 1 was a brown, highly transparent liquid. In Figure 2, when a certain amount of the PVP-fullerene complex aqueous solution in Comparative Area 1 was weighed into a test tube and the test tube was tilted, it was cloudy to the point where the printing on the paper underneath was difficult to read, whereas the PVP-fullerene complex aqueous solution in Experimental Area 1 was so clear that the printing could be identified at the top of the solution when the test tube was tilted and the amount of liquid decreased.

[0038] The above results indicate that the cause of turbidity in the PVP-fullerene complex and the aqueous solution of the PVP-fullerene complex is the aromatic hydrocarbon toluene.

[0039] Example 2 Comparison of Clarity of PVP-Fullerene Complex Aqueous Solutions with Different Residual Amounts of Toluene PVP-fullerene complexes with different residual amounts of toluene were prepared, and the turbidity of the compositions in which these were dissolved was compared.

[0040] (Example 2) - Test Areas - Test area 2: toluene concentration 1000 ppm Test area 3: toluene concentration 2000 ppm Comparison area 2: toluene concentration 3000 ppm Test area 3: toluene concentration 4000 ppm Test area 4: toluene concentration 5000 ppm

[0041] (Example 2) - Materials - PVP-fullerene complex: Complies with the "Guidelines for Residual Solvents in Pharmaceuticals" and has a residual toluene content of 890 ppm or less. Hereinafter, this will be referred to as a guideline-compliant product. Toluene: Special grade toluene reagent (manufactured by Wako Pure Chemical Industries, Ltd.)

[0042] Example 2 - Preparation of PVP-fullerene complex aqueous solutions with different residual toluene amounts - 2 g of PVP-fullerene complex (guideline-compliant product) was weighed into a screw-cap test tube, and toluene was added to each test group in 1000 ppm increments from 1000 ppm to 5000 ppm. The mixture was then mixed and allowed to stand for a certain period of time before being used for testing. 0.5 g of the mixed powder was added to 5 mL of distilled water, mixed, and allowed to stand overnight. The degree of turbidity was evaluated visually. The evaluation method was the same as in Example 1, where a certain amount was weighed into a test tube, the test tube was placed at an angle, and the clarity was evaluated based on the readability of the printing on the paper underneath.

[0043] (Example 2) - Results - The turbidity of the PVP-fullerene complex aqueous solutions in Experimental Areas 2-3 and Comparative Areas 2-4 is shown in Figure 3. Experimental Areas 2 and 3 were so clear that the printed characters could be identified at the top of the solution when the test tube was tilted and the amount of liquid decreased. This shows that when the PVP-fullerene complex aqueous solution contains 3000 ppm or more of toluene, turbidity is observed in the solution, and clarity increases at less than 3000 ppm.

[0044] From the above results, by reducing the toluene content of the PVP-fullerene complex aqueous solution to less than 3000 ppm, the PVP-fullerene complex aqueous solution exhibited high quality of clarity without becoming cloudy.

[0045] The results of Examples 1 and 2 showed that toluene was the cause of turbidity in the PVP-fullerene complex and the PVP-fullerene complex aqueous solution. Furthermore, it was shown that the inclusion of toluene of 30,000 ppm or more in the PVP-fullerene complex and 3,000 ppm or more in the PVP-fullerene complex aqueous solution reduced the clarity and was identified as turbidity.

[0046] As explained above, according to the present invention, it has been clarified that the PVP-fullerene complex and its aqueous solution lose their clarity and become cloudy when the aromatic hydrocarbon, toluene, used as a solvent for fullerene, remains at a certain concentration or more. By reducing the toluene concentration in the PVP-fullerene complex to a certain concentration or less, it is possible to provide the expected physiological activity without impairing the appearance of cosmetics, etc.

Claims

1. A PVP-fullerene complex or topical composition having a residual amount of aromatic hydrocarbons of less than 30,000 ppm.

2. The PVP-fullerene complex or topical composition according to (1) above, wherein the aromatic hydrocarbon is toluene.

3. A PVP-fullerene complex aqueous solution or topical composition containing less than 3,000 ppm of residual aromatic hydrocarbons.

4. The aqueous solution or topical composition for PVP-fullerene complex according to (3) above, wherein the aromatic hydrocarbon is toluene.

5. A method for clarifying a PVP-fullerene composite composition containing less than 30,000 ppm of aromatic hydrocarbons, in which the aromatic hydrocarbon content is adjusted to less than 30,000 ppm in a PVP-fullerene composite composition containing 30,000 ppm or more of aromatic hydrocarbons.

6. A method for clarifying a PVP-fullerene complex aqueous solution or topical composition containing 3000 ppm or more of aromatic hydrocarbons, by adjusting the aromatic hydrocarbon content of the PVP-fullerene complex aqueous solution or topical composition to less than 3000 ppm.

7. A method for producing a PVP-fullerene complex composition, which includes a step of evaporating a mixed liquid of fullerenes dissolved in aromatic hydrocarbons and PVP dissolved in ethanol to dryness, and which further includes a step of adjusting the aromatic hydrocarbon content in the PVP-fullerene complex composition to 30,000 ppm.

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