Stable high caffeine content compositions

Abstract

The invention provides a stable high-content caffeine composition. The stable high-content caffeine composition comprises the following components in percentage by weight: 0.1-20% of caffeine; from 5 to 40% by weight of a polydimethylsiloxane / vinyl polydimethylsiloxane cross-linked polymer; 2 to 15% by weight of a polydimethylsiloxane; the emulsifying agent is selected from the group consisting of cetyl PEG (polyethylene glycol) / PPG-10 / 1 polydimethylsiloxane, lauryl PEG (polyethylene glycol)-9 polydimethylsilyloxyethyl polydimethylsiloxane or a combination of the cetyl PEG / PPG-10 / 1 polydimethylsiloxane and the lauryl PEG-9 polydimethylsilyloxyethyl polydimethylsiloxane; 0.5 to 10% by weight of cetearyl alcohol ethyl hexanoate; 5 to 60% by weight of a polyol selected from the group consisting of: propylene glycol, butanediol, glycerol, methylpropanediol, or a combination thereof; and water. The invention also relates to a preparation method of the stable high-content caffeine composition.

Description

Technical Field

[0001] The invention relates to the fields of fine chemistry and cosmetics, and in particular to a composition with a stable high content of caffeine, a preparation method and an application thereof. Background Art

[0002] Caffeine is a xanthine alkaloid compound and a central nervous system stimulant. In addition to the cardiovascular and nervous systems in the human body, the skin can also be affected by it. Currently, caffeine mainly comes from coffee beans, but it is not the only source. Various teas also contain caffeine, among which black tea and oolong tea have higher caffeine content, which is why some people can't sleep even after drinking milk tea.

[0003] Caffeine can stimulate metabolism and accelerate local microcirculation. Now more and more products are adding caffeine, especially eye cream products. Caffeine can shrink capillaries, promote blood circulation in the skin, and speed up the discharge of metabolites accumulated due to slow metabolism through the circulatory system, allowing fresh oxygen to reach the skin tissue in time. Therefore, caffeine can relieve dark circles caused by poor metabolism of eye tissues, and has a certain effect on vascular dark circles caused by staying up late and lack of sleep, but it is powerless against pigmented, structural and mixed dark circles.

[0004] In addition, "caffeine" can increase the concentration of extracellular ions and help cells excrete excess water, thereby eliminating skin edema. Drinking water before going to bed, poor rest or excessive mental stress can easily cause eye or facial edema. Skin care products containing caffeine can help eliminate edema and restore the skin to normal.

[0005] Some brands also add caffeine to their products as an antioxidant, but from the test results, the effect is still much inferior to that of traditional professional antioxidants. In skin care products, the anti-inflammatory and antioxidant effects of "caffeine" can only serve as auxiliary functions. Studies have shown that caffeine can penetrate the hair roots, promote blood circulation near the hair follicles, and promote hair growth. It can also strengthen the hair roots and prevent hair from thinning. However, it should be noted that both of these effects require caffeine to come into direct contact with the scalp. Caffeine only needs to be in contact with the scalp for 2 minutes before it can take effect, but drinking coffee does not have a similar effect.

[0006] Current studies have shown that caffeine has multiple physiological functions such as anti-oxidation, hair growth, eliminating skin edema, promoting microcirculation and reducing dark circles. However, the solubility of caffeine in water at 25°C is about 21.7mg / ml, which leads to precipitation in aqueous solution. Therefore, it is difficult to use caffeine effectively in skin care products, especially when adding high levels of caffeine. Common volume expansion or encapsulation technologies cannot solve this problem.

[0007] For example, KR10-2213669 discloses a caffeine solubilizing composition, comprising caffeine, nicotinamide and ethyl vanillin, and the weight ratio of nicotinamide to ethyl vanillin is 1:4 to 1:6. For example, JP2009280557 discloses an aqueous composition with a high caffeine content, maintaining the solubility of caffeine and having a stable pharmacological effect, containing caffeine and vanillin at a concentration of up to 3-40% by weight. For example, CN104039303 discloses a cosmetic composition containing high concentrations of caffeine and nicotinamide, which can prevent the precipitation of caffeine at low temperatures, thereby containing high concentrations of caffeine that are effective in promoting fat decomposition. For example, KR10-2017-0138183 discloses a solubilizing system of high-content caffeine with poor water solubility, a system for increasing percutaneous absorption by solubilizing high-content caffeine using a low-molecular-weight complex such as urea or sodium salicylate, and a high-functional cosmetic composition containing it for acne, atopic dermatitis, etc. For example, KR10-2017-0138179 discloses a solubilization system of high-content coffee-derived natural caffeine that is insoluble in water, which ensures enhanced percutaneous absorption by dissolving high-content coffee-derived natural caffeine using a water solvent as a low molecular weight complex (such as urea or sodium salicylate). The composition is used for acne, atopy, etc. However, the above reports all improve the solubility of caffeine from component or single ingredient experiments, and do not study the stability of caffeine in the application formula system.

[0008] In contrast, the present invention not only screens out a carrier system that can stabilize caffeine, but also makes a great breakthrough in the stable expression of caffeine content, and further quantifies the contribution of the carrier system to the stability of caffeine. Summary of the invention

[0009] In one aspect, the present invention provides a stable high-caffeine composition comprising:

[0010] 0.1-20% by weight of caffeine;

[0011] 5-40 wt.% dimethicone / vinyl dimethicone crosspolymer;

[0012] 2-15 wt% polydimethylsiloxane;

[0013] 0.01-5 wt% of an emulsifier, wherein the emulsifier is selected from: cetyl PEG / PPG-10 / 1 polydimethylsiloxane, lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, or a combination thereof;

[0014] 0.5-10% by weight of cetearyl ethylhexanoate;

[0015] 5-60 wt% of a polyol selected from the group consisting of propylene glycol, butylene glycol, glycerol, methylpropanediol, or a combination thereof; and water.

[0017] In a preferred embodiment, the composition of the present invention further comprises 0.01-0.7 wt % of a preservative.

[0018] In a preferred embodiment, the composition of the present invention comprises 2-6.5% by weight of caffeine.

[0019] In a preferred embodiment, the compositions of the present invention comprise 10-35% by weight of dimethicone / vinyl dimethicone crosspolymer.

[0020] In a preferred embodiment, the composition of the present invention comprises 5-15% by weight of polydimethylsiloxane.

[0021] In a preferred embodiment, the composition of the present invention comprises 0.5-5% by weight of an emulsifier.

[0022] In a preferred embodiment, the composition of the present invention comprises 30-60% by weight of polyol.

[0023] In a preferred embodiment, the composition of the present invention is in the form of a gel.

[0024] In another aspect, the present invention also relates to a method for preparing the composition, comprising the following steps:

[0025] (a) weighing caffeine and polyol, homogenizing and obtaining an alcohol phase;

[0026] (b) mixing dimethicone / vinyl dimethicone crosspolymer, dimethicone, an emulsifier and cetearyl ethylhexanoate as an oil phase;

[0027] (c) adding dropwise the alcohol phase of step (a) to the oil phase of step (b) and homogenizing;

[0028] (d) add water and mix,

[0029] (e) After standing, the composition of the present invention is obtained.

[0030] In a preferred embodiment, the homogenization in step (a) comprises 2500-3000 rpm and homogenization for 5-6 minutes.

[0031] In a preferred embodiment, the homogenization in step (c) comprises 2500-3000 rpm and homogenization for 5-15 minutes. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1The infrared spectra of the caffeine aqueous solution precipitate and the infrared spectra of the reference substance are shown, corresponding to the caffeine-containing aqueous solutions of Examples 4-8, respectively. DETAILED DESCRIPTION

[0033] The object of the present invention is to provide a carrier system with a stable high content of caffeine. The carrier dosage form prepared according to the provided formula and preparation method can not only stabilize the state of caffeine in skin care products, but also ensure the active content of caffeine.

[0034] In order to provide a more concise description, some quantitative expressions given herein are not modified by the term "about". It should be understood that, whether or not the term "about" is explicitly used, each quantity given herein is intended to refer to the actual given value, and is also intended to refer to the approximate values ​​of these given values ​​that can be reasonably inferred by ordinary technicians in the field, including the approximate values ​​of these given values ​​caused by experimental and / or measurement conditions.

[0035] caffeine

[0036] Caffeine has many physiological functions, such as anti-oxidation, hair growth, eliminating skin edema, promoting microcirculation and reducing dark circles. However, the solubility of caffeine in water at 25°C is about 21.7mg / ml, which leads to precipitation in aqueous solution. Therefore, it is difficult to use caffeine effectively in skin care products, especially when adding high content of caffeine, which cannot be solved by common volume expansion or encapsulation technology.

[0037] In some embodiments, the composition of the present invention comprises 0.1-20% by weight of caffeine. Preferably, the composition of the present invention comprises 0.1-15% by weight of caffeine.

[0038] Preferably, the composition of the present invention may contain a high content of caffeine. For example, the composition of the present invention contains 2-6.5 wt% caffeine, preferably 2.5-6.5 wt%, more preferably 4.5-6.5 wt% caffeine.

[0039] In a specific embodiment, the present invention uses encapsulated caffeine (caffeine 50%) available from AXIALYS INNOVATIONS under the trade name CAFFENERGY 50C.

[0040] Compositions with high caffeine content

[0041] The present invention provides a carrier system capable of carrying a high content of caffeine. In a preferred embodiment, the carrier system capable of carrying a high content of caffeine is a gel system.

[0042] The composition of the present invention comprises a silicone elastomer. In some embodiments, the silicone elastomer is selected from: dimethicone / vinyl dimethicone crosspolymer, dimethicone, or a combination thereof.

[0043] In some embodiments, the compositions of the present invention comprise 5-40% by weight of dimethicone / vinyl dimethicone crosspolymer. Preferably, the compositions of the present invention comprise 10-35% by weight of dimethicone / vinyl dimethicone crosspolymer. More preferably, the compositions of the present invention comprise 25-30% by weight of dimethicone / vinyl dimethicone crosspolymer.

[0044] In some embodiments, the composition of the present invention comprises 2-15% by weight of polydimethylsiloxane. Preferably, the composition of the present invention comprises 5-15% by weight of polydimethylsiloxane. More preferably, the composition of the present invention comprises 10% by weight of polydimethylsiloxane.

[0045] In a specific embodiment, the present invention uses a polydimethylsiloxane / vinyl polydimethylsiloxane cross-linked polymer with the trade name KSG-19 purchased from Xinyue Silicone International Trading (Shanghai) Co., Ltd.

[0046] In a specific embodiment, the present invention uses a product purchased from Wacker Chemical (China) Co., Ltd. under the trade name DM 1PLUS dimethicone.

[0047] The composition of the present invention comprises an emulsifier. In some embodiments, the emulsifier is selected from: cetyl PEG / PPG-10 / 1 dimethicone, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, or a combination thereof.

[0048] In some embodiments, the composition of the present invention comprises 0.01-5 wt % of an emulsifier. Preferably, the composition of the present invention comprises 0.5-5 wt % of an emulsifier. More preferably, the composition of the present invention comprises 0.5-2 wt % of an emulsifier.

[0049] In some embodiments, the composition of the present invention comprises 0.01-5% by weight of cetyl PEG / PPG-10 / 1 dimethicone. Preferably, the composition of the present invention comprises 0.5-5% by weight of cetyl PEG / PPG-10 / 1 dimethicone. More preferably, the composition of the present invention comprises 0.5-2% by weight of cetyl PEG / PPG-10 / 1 dimethicone.

[0050] In some embodiments, the composition of the present invention comprises 0.01-5% by weight of Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone. Preferably, the composition of the present invention comprises 0.5-5% by weight of Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone. More preferably, the composition of the present invention comprises 0.5-2% by weight of Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone.

[0051] In a specific embodiment, the present invention uses a product purchased from Evonik Operations GmbH under the trade name EM 90 Cetyl PEG / PPG-10 / 1 Dimethicone.

[0052] In a specific embodiment, the present invention uses KF-6038 Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone provided by Shin-Etsu Silicone International Trading (Shanghai) Co., Ltd.

[0053] The composition of the present invention comprises cetearyl ethylhexanoate.

[0054] In some embodiments, the composition of the present invention comprises 0.5-10% by weight of cetearyl ethylhexanoate. Preferably, the composition of the present invention comprises 0.5-8% by weight of cetearyl ethylhexanoate. More preferably, the composition of the present invention comprises 1-5% by weight of cetearyl ethylhexanoate.

[0055] In a specific embodiment, the present invention adopts the trade name of Cetearyl Ethylhexanoate.

[0056] The composition of the present invention comprises a polyol. In some embodiments, the polyol is selected from: propylene glycol, butylene glycol, glycerol, methyl propylene glycol or a combination thereof. In a preferred embodiment, the polyol is 1,3-propylene glycol, 1,3-butylene glycol, methyl propylene glycol or a combination thereof.

[0057] In some embodiments, the composition of the present invention comprises 30-60 wt% polyol. Preferably, the composition of the present invention comprises 35-50 wt% polyol.

[0058] In some embodiments, the composition of the present invention comprises 5-60 wt% propylene glycol. Preferably, the composition of the present invention comprises 10-60 wt% propylene glycol.

[0059] In some embodiments, the composition of the present invention comprises 5-60 wt% butanediol. Preferably, the composition of the present invention comprises 10-60 wt% butanediol.

[0060] In some embodiments, the composition of the present invention comprises 5-60% by weight of glycerol. Preferably, the composition of the present invention comprises 10-60% by weight of glycerol.

[0061] In some embodiments, the composition of the present invention comprises 5-60 wt% methylpropanediol. Preferably, the composition of the present invention comprises 10-60 wt% methylpropanediol.

[0062] The compositions of the present invention include a preservative. In some embodiments, the preservative is phenoxyethanol.

[0063] In some embodiments, the composition of the present invention comprises 0.01-0.7 wt % of a preservative. Preferably, the composition of the present invention comprises 0.2-0.6 wt % of a preservative. More preferably, the composition of the present invention comprises 0.5 wt % of a preservative.

[0064] The composition of the present invention comprises water. In some embodiments, the composition of the present invention comprises 1-80% by weight of water. Preferably, the composition of the present invention comprises 1-10% by weight of water. More preferably, the composition of the present invention comprises 2% by weight of water.

[0065] The present invention is further described below in conjunction with specific examples. It is necessary to point out that the examples are only used to further illustrate the present invention and cannot be construed as limiting the scope of the present invention. Those skilled in the art can make some non-essential improvements and adjustments based on the content of the present invention described above. The test methods in the following examples that do not specify specific conditions are usually based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, all percentages and parts are by weight.

[0066] Preparation method of composition

[0067] The present invention also relates to a method for preparing a high-content caffeine composition. Specifically, the method comprises the following steps:

[0068] (a) weighing caffeine and polyol, homogenizing and obtaining an alcohol phase;

[0069] (b) mixing a silicone elastomer, an emulsifier and cetearyl ethylhexanoate as an oil phase;

[0070] (c) adding dropwise the alcohol phase of step (a) to the oil phase of step (b) and homogenizing;

[0071] (d) add water and mix,

[0072] (e) After standing, the composition of the present invention is obtained.

[0073] In a preferred embodiment, the homogenization in step (a) comprises 2500-3000 rpm and homogenization for 5-6 minutes.

[0074] In a preferred embodiment, the homogenization in step (c) comprises 2500-3000 rpm and homogenization for 5-15 minutes.

[0075] In a preferred embodiment, the step of adding a preservative is further included before step (d).

[0076] Example

[0077] The experimental materials used in the embodiments of the present invention are as follows:

[0078] Dimethicone / vinyl dimethicone crosspolymer, trade name KSG-19, purchased from Xinyue Silicone International Trading (Shanghai) Co., Ltd.

[0079] Polydimethylsiloxane, trade name DM 1PLUS, purchased from Wacker Chemical (China) Co., Ltd.;

[0080] Cetyl PEG / PPG-10 / 1 Polydimethylsiloxane, trade name EM 90, purchased from Evonik Operations GmbH;

[0081] Lauryl PEG-9 polydimethylsiloxyethyl dimethicone, trade name KF-6038, sample provided by Shin-Etsu Silicone International Trading (Shanghai) Co., Ltd.;

[0082] Cetearyl Ethylhexanoate, trade name Purchased from Dezhixin Flavors & Fragrances (Nantong) Co., Ltd.

[0083] 1,3-propylene glycol, trade name Propanediol, purchased from Primient Covation LLC;

[0084] 1,3-Butylene Glycol, trade name 1,3-Butylene Glycol, purchased from DAICEL CORPORATION;

[0085] Glycerin, trade name MASCEROL Glycerine 99.7% USP, purchased from PT MUSIM MAS;

[0086] Methylpropanediol, trade name AFDiol, purchased from Activa-Finsol Chemicals, Inc.;

[0087] Encapsulated caffeine (caffeine 50%), trade name CAFFENERGY 50C, purchased from AXIALYS INNOVATIONS;

[0088] Phenoxyethanol, trade name NEOLONE TM PH 100 preservative was purchased from Weimaikong Biotechnology (Shanghai) Co., Ltd.

[0089] Example 1: Preparation of a Caffeine-Containing Aqueous Solution

[0090] Weigh 1 part by mass of encapsulated caffeine (0.5 parts by mass of caffeine) and 80 parts by mass of deionized water, mix and dissolve, stir at room temperature at a speed of 100 rpm until completely dissolved or mixed evenly; add deionized water to make up to 100, continue to stir at a speed of 100 rpm for 10-20 minutes; then let stand at room temperature for 12 hours for use.

[0091] Example 2: Preparation of a Caffeine-Containing Aqueous Solution

[0092] Weigh 2 parts by mass of encapsulated caffeine (1 part by mass of caffeine) and 80 parts by mass of deionized water, mix and dissolve, and stir at room temperature at a speed of 100 rpm until all dissolved or mixed evenly; add deionized water to make up to 100, and continue to stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for use.

[0093] Example 3: Preparation of a Caffeine-Containing Aqueous Solution

[0094] Weigh 4 parts by mass of encapsulated caffeine (2 parts by mass of caffeine) and 80 parts by mass of deionized water, mix and dissolve, and stir at room temperature at a speed of 100 rpm until all dissolved or mixed evenly; add deionized water to make up to 100, and continue to stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for use.

[0095] Example 4: Preparation of a Caffeine-Containing Aqueous Solution

[0096] Weigh 6 parts by mass of encapsulated caffeine (3 parts by mass of caffeine) and 80 parts by mass of deionized water, mix and dissolve, and stir at room temperature at a speed of 100 rpm until all dissolved or mixed uniformly; add deionized water to make up to 100, and continue to stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for use.

[0097] Example 5: Preparation of a Caffeine-Containing Aqueous Solution

[0098] Weigh 8 parts by mass of encapsulated caffeine (4 parts by mass of caffeine) and 80 parts by mass of deionized water, mix and dissolve, and stir at room temperature at a speed of 100 rpm until all dissolved or mixed uniformly; add deionized water to make up to 100, and continue to stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for use.

[0099] Example 6: Preparation of a Caffeine-Containing Aqueous Solution

[0100] Weigh 10 parts by mass of encapsulated caffeine (5 parts by mass of caffeine) and 80 parts by mass of deionized water, mix and dissolve, and stir at room temperature at a speed of 100 rpm until all dissolved or mixed evenly; add deionized water to make up to 100, and continue to stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for use.

[0101] Example 7: Preparation of a Caffeine-Containing Aqueous Solution

[0102] Weigh 12 parts by mass of encapsulated caffeine (6 parts by mass of caffeine) and 80 parts by mass of deionized water, mix and dissolve, and stir at room temperature at a speed of 100 rpm until all dissolved or mixed evenly; add deionized water to make up to 100, and continue to stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for use.

[0103] Example 8: Preparation of a Caffeine-Containing Aqueous Solution

[0104] Weigh 15 parts by mass of encapsulated caffeine (7.5 parts by mass of caffeine) and 80 parts by mass of deionized water, mix and dissolve, and stir at room temperature at a speed of 100 rpm until all dissolved or mixed evenly; add deionized water to make up to 100, and continue to stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for use.

[0105] Test Example 1: Product viscosity test and high and low temperature stability test

[0106] After measuring the viscosity of the systems of Examples 1-8, the high and low temperature stability thereof was investigated.

[0107] Use BROOKFIELD RVDVC digital viscometer (with RV and T-type rotors), sample test temperature: 25℃, constant temperature for 4h, sample test container: try to use the same specification beaker (180ml bottle) when testing different batches of the same sample; reading recording time: 60s for LV / RV type rotors; 90s for T-type rotors; before measuring the sample, make sure there is no bubble interference. Select the corresponding rotor and speed according to the standard. After taking the sample out of the thermostatic bath, immediately measure its viscosity with a rotational viscometer. When selecting LV and RV rotors, insert the rotor obliquely into the sample so that the liquid level is just in the depression of the rotor, and keep the rotor wall free of bubbles; when selecting T-type rotors, make the rotor just close to the liquid surface, and select a certain up and down movement distance so that the rotor has enough up and down space without touching the bottom of the beaker and causing damage. Record the viscosity result after the reading stabilizes (or after the time specified by the standard).

[0108] The high and low temperature stability evaluation method is as follows: Place the aqueous sample prepared in Examples 1-8 in a thermostat stable at high temperature (48°C, 25°C, 4°C) and observe for 30 days. Observe whether the sample has solid precipitation, jelly, stratification, etc. If the sample is normal and unchanged before and after a certain time within 30 days, it means "passed", the appearance of fixed substances means "precipitation", the phenomenon that the material solidifies and is not easy to flow means "jelly", and the phenomenon of two layers of liquid above and below means "stratification". The results are shown in the following table.

[0109] Table 1 shows the stability study and viscosity results of Examples 1-8.

[0110] Table 1

[0111]

[0112]

[0113] Conclusion: Prepare an aqueous solution containing caffeine, and examine the stability of caffeine in the aqueous solution system at different concentrations. The above experimental results show that the stability of the aqueous solution containing 2 parts by mass of encapsulated caffeine (1 part by mass of caffeine) is good, which meets the qualified requirements of consumers for the stability of aqueous dosage forms. However, in terms of the stability of aqueous solutions with a content of more than 2 parts by mass of encapsulated caffeine (1 part by mass of caffeine), the dosage form shows precipitation or stratification at different temperatures, and the dosage form is very unstable.

[0114] Test Example 2: Caffeine content test of products after high temperature treatment

[0115] Test sample: Caffeine-containing aqueous solution prepared in Example 1-8 (heated at 48°C for one month)

[0116] (1) Detection instrument: Waters ARC high performance liquid chromatograph with diode array detector, or equivalent model.

[0117] (2) Testing conditions:

[0118] Chromatographic column: Agilent SB-C18 column (250 mm × 4.6 mm, 5 μm, Agilent).

[0119] Mobile phase: acetonitrile: water (pH adjusted to 2.5 with phosphoric acid) = 30:70.

[0120] Detection wavelength: 270nm.

[0121] Flow rate: 1.0 mL / min; injection volume: 10 μL; column temperature: 30°C.

[0122] (3) Standard curve: Weigh 0.1g (accurate to 0.1mg) of raw material-encapsulated caffeine (caffeine content is 50%) into a 50mL volumetric flask, dissolve it in water and make up to volume, shake well, and prepare a standard stock solution. Take 0.1mL, 0.2mL, 0.5mL, 1mL, and 2mL of the above standard stock solution into a 10mL volumetric flask, make up to volume with mobile phase, and prepare standard working solutions with caffeine contents of 10μg / mL, 20μg / mL, 50μg / mL, 100μg / mL, and 200μg / mL, respectively. Perform injection detection according to the above detection conditions (2), draw a standard curve with peak area as the ordinate and caffeine content as the abscissa, and calculate the linear regression equation of the standard curve.

[0123] (4) Sample processing and detection: Take 0.1g of sample (accurate to 0.1mg) in a 50mL stoppered colorimetric tube, add about 40mL of mobile phase, and ultrasonically extract for 20min. Use mobile phase to make up to volume, shake well, and filter part of the liquid through a 0.45μm filter membrane to obtain the test solution. Perform sample injection detection according to the above detection conditions (2), and quantify the sample on the standard curve. The caffeine response value in the sample solution should be within the linear range of the standard curve.

[0124] (5) Calculation formula: external standard method, the calculation formula for caffeine content in the sample is:

[0125]

[0126] Where:

[0127] X——mass fraction of caffeine in the sample, %;

[0128] C——The concentration of caffeine in the test solution obtained from the standard curve, in micrograms per milliliter (μg·mL-1);

[0129] V——total volume of the sample after dilution, in milliliters (mL);

[0130] M——sample mass, in grams (g);

[0131] Table 2 shows the caffeine content of the aqueous solutions of Examples 1-8 after high temperature treatment.

[0132] Table 2

[0133] sample pH Caffeine Content% Recovery rate % Example 1 4.9 0.50 100.00％ Example 2 4.9 0.98 98.00％ Example 3 5.0 2.00 100.00％ Example 4 5.0 1.76 58.67％ Example 5 5.3 2.36 59.00％ Example 6 5.7 1.48 29.60％ Example 7 6.0 1.80 30.00％ Example 8 6.4 2.35 31.33％

[0134] Conclusion: Aqueous solutions containing caffeine were prepared, and the effective content of caffeine after high temperature in aqueous solutions with different concentrations of caffeine was investigated. Taking into account test deviation and addition loss, it is generally believed that a recovery rate of more than 90% is the effective concentration of the active substance, and a recovery rate below 90% is considered to have a risk of precipitation and deterioration. After high temperature in aqueous solutions with different concentrations of caffeine, the test contents of Examples 4-8 were all lower than 90% of the added amount, and it was believed that the caffeine content and efficacy decreased due to precipitation or stratification, which further indicated that high-concentration encapsulated caffeine could not be stable in this system.

[0135] Test Example 3: Analysis and Testing of Caffeine Aqueous Solution Precipitates

[0136] (1) Testing instruments: Nicolet iS10 Fourier transform infrared spectrometer (Thermo Scientific); SMARTiTR diamond crystal accessory.

[0137] (2) Treatment of precipitate samples: Take an appropriate amount of precipitate, wash it twice with deionized water, and discard the supernatant. Dry the precipitate at 80°C to obtain a solid sample for infrared spectrum collection.

[0138] (3) Collect infrared spectrum: Install the SMART iTR diamond crystal accessory. Start the infrared spectrometer, allow the instrument to warm up and stabilize, and collect a blank background. Place a small amount of solid sample or reference on the diamond crystal, press it tightly, and collect an infrared spectrum. After the test is completed, wipe off the sample or reference on the diamond crystal. Repeat the above steps to collect other samples.

[0139] (4) Spectrum comparison: Compare the infrared spectrum of the precipitate sample with the infrared spectrum of the reference substance, such as Figure 1 shown.

[0140] Conclusion: The precipitate of caffeine aqueous solution was analyzed by infrared spectroscopy and found to be caffeine, which caused instability in the system.

[0141] Example 9: Preparation of a gel containing caffeine

[0142] Weigh 4 parts by mass of encapsulated caffeine (2 parts by mass of caffeine) and 46.5 parts by mass of 1,3-propylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, as the alcohol phase. Take another beaker and mix 30 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane cross-linked polymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl ethylhexanoate and 2 parts by mass of cetyl PEG / PPG-10 / 1 polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine dispersed in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for standby use.

[0143] Example 10: Preparation of a gel containing caffeine

[0144] Weigh 4 parts by mass of encapsulated caffeine (2 parts by mass of caffeine) and 46.5 parts by mass of 1,3-propylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, which is used as the alcohol phase. Take another beaker and mix 30 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane crosspolymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for standby use.

[0145] Example 11: Preparation of a gel containing caffeine

[0146] Weigh 5 parts by mass of encapsulated caffeine (2.5 parts by mass of caffeine) and 45.5 parts by mass of 1,3-propylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, which is used as the alcohol phase. Take another beaker and mix 30 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane crosspolymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine dispersed in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for standby use.

[0147] Example 12: Preparation of a gel containing caffeine

[0148] Weigh 5 parts by mass of encapsulated caffeine (2.5 parts by mass of caffeine) and 45.5 parts by mass of 1,3-butylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, which is used as the alcohol phase. Take another beaker and mix 30 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane crosspolymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for standby use.

[0149] Example 13: Preparation of a gel containing caffeine

[0150] Weigh 5 parts by mass of encapsulated caffeine (2.5 parts by mass of caffeine) and 45.5 parts by mass of methyl propanediol and homogenize at room temperature at 2500-3000 rpm. After homogenization for 5-6 minutes, the mixture is uniform and free of particles as the alcohol phase. Take another beaker and mix 30 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane cross-linked polymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane to make it uniform as the oil phase. Slowly drop the polyol solution of caffeine dispersed in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then stand at room temperature for 12 hours for standby use.

[0151] Example 14: Preparation of a gel containing caffeine

[0152] Weigh 5 parts by mass of encapsulated caffeine (2.5 parts by mass of caffeine) and 45.5 parts by mass of glycerol and homogenize at room temperature at 2500-3000 rpm. After homogenization for 5-6 minutes, the mixture is uniform and free of particles as the alcohol phase. Take another beaker and mix 30 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane cross-linked polymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane to form an oil phase. Slowly drop the polyol solution of caffeine in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then stand at room temperature for 12 hours for standby use.

[0153] Test Example 4: Product viscosity test and high and low temperature stability test

[0154] After measuring the viscosity of the systems of Examples 9-14, the high and low temperature stability thereof was investigated.

[0155] Use BROOKFIELD RVDVC digital viscometer (with RV and T-type rotors), sample test temperature: 25℃, constant temperature for 4h, sample test container: try to use beakers of the same specification (180ml bottle) when testing different batches of the same sample; reading recording time: 60s for LV / RV type rotors; 90s for T-type rotors; before measuring the sample, make sure there is no bubble interference. Select the corresponding rotor and speed according to the standard. After taking the sample out of the thermostatic bath, immediately measure its viscosity with a rotational viscometer. When selecting LV and RV rotors, insert the rotor obliquely into the sample so that the liquid level is just in the depression of the rotor, and keep the rotor wall free of bubbles; when selecting T-type rotors, make the rotor just close to the liquid surface, and select a certain up and down movement distance so that the rotor has enough up and down space without touching the bottom of the beaker and causing damage. Record the viscosity result after the reading stabilizes (or after the time specified by the standard).

[0156] The high and low temperature stability evaluation method is as follows: Place the aqueous sample prepared in Examples 9-14 in a thermostat stable at high temperature (48°C, 25°C, 4°C) and observe for 30 days. Observe whether the sample has solid precipitation, jelly, stratification, etc. If the sample is normal and unchanged before and after a certain time within 30 days, it means "passed", the appearance of fixed substances means "precipitation", the phenomenon that the material solidifies and is not easy to flow means "jelly", and the phenomenon of two layers of liquid above and below means "stratification". The results are shown in the following table.

[0157] Table 3 shows the stability study and viscosity results for Examples 9-14.

[0158] Table 3

[0159]

[0160] Conclusion: Gels containing caffeine were prepared, and the stability of gels with different emulsifiers and different polyols was investigated. The above experimental results show that the stability of gels containing 4-5 parts by mass of encapsulated caffeine (2-2.5 parts by mass of caffeine) is good, and the gel with only glycerol as the alcohol phase shows a slight decrease in viscosity at high temperature. The others all meet the qualified requirements of consumers for the stability of gel dosage forms. However, in the comparison of emulsifiers of the same mass, the gel prepared by lauryl PEG-9 polydimethylsiloxyethyl polydimethicone is significantly higher in viscosity and more stable than the gel prepared by cetyl PEG / PPG-10 / 1 polydimethicone.

[0161] Test Example 5: Caffeine content test of products after high temperature treatment

[0162] Test sample: Caffeine-containing aqueous solution prepared in Examples 9-14 (heated at 48°C for one month)

[0163] (1) Detection instrument: Waters ARC high performance liquid chromatograph with diode array detector, or equivalent model.

[0164] (2) Testing conditions:

[0165] Chromatographic column: Agilent SB-C18 column (250 mm × 4.6 mm, 5 μm, Agilent).

[0166] Mobile phase: acetonitrile: water (pH adjusted to 2.5 with phosphoric acid) = 30:70.

[0167] Detection wavelength: 270nm.

[0168] Flow rate: 1.0 mL / min; injection volume: 10 μL; column temperature: 30°C.

[0169] (3) Standard curve: Weigh 0.1g (accurate to 0.1mg) of raw material-encapsulated caffeine (caffeine content is 50%) into a 50mL volumetric flask, dissolve it in water and make up to volume, shake well, and prepare a standard stock solution. Take 0.1mL, 0.2mL, 0.5mL, 1mL, and 2mL of the above standard stock solution into a 10mL volumetric flask, make up to volume with mobile phase, and prepare standard working solutions with caffeine contents of 10μg / mL, 20μg / mL, 50μg / mL, 100μg / mL, and 200μg / mL, respectively. Perform injection detection according to the above detection conditions (2), draw a standard curve with peak area as the ordinate and caffeine content as the abscissa, and calculate the linear regression equation of the standard curve.

[0170] (4) Sample processing and detection: Take 0.1g of sample (accurate to 0.1mg) in a 50mL stoppered colorimetric tube, add about 40mL of mobile phase, and ultrasonically extract for 20min. Use mobile phase to make up to volume, shake well, and filter part of the liquid through a 0.45μm filter membrane to obtain the test solution. Perform sample injection detection according to the above detection conditions (2), and quantify the sample on the standard curve. The caffeine response value in the sample solution should be within the linear range of the standard curve.

[0171] (5) Calculation formula: external standard method, the calculation formula for caffeine content in the sample is:

[0172]

[0173] Where:

[0174] X——mass fraction of caffeine in the sample, %;

[0175] C——The concentration of caffeine in the test solution obtained from the standard curve, in micrograms per milliliter (μg·mL-1);

[0176] V——total volume of the sample after dilution, in milliliters (mL);

[0177] M——sample mass, in grams (g);

[0178] Table 4 shows the caffeine content of the aqueous solutions of Examples 9-14 after high temperature treatment.

[0179] Table 4

[0180] sample pH Caffeine Content% Recovery rate % Example 9 4.5 1.89 94.50％ Example 10 4.5 1.94 97.00％ Embodiment 11 4.8 2.5 100.00％ Example 12 4.9 2.5 100.00％ Embodiment 13 4.8 2.38 95.20％ Embodiment 14 4.8 2.47 98.80％

[0181] Conclusion: Gels containing caffeine were prepared, and the effective caffeine content of gels with different emulsifiers and different polyols after high temperature was investigated. Considering the test deviation and addition loss, it is generally believed that a recovery rate of more than 90% is the effective concentration of the active substance, and a recovery rate below 90% is considered to have a risk of precipitation and deterioration. After high temperature, the test contents of Examples 9-14 of gels with different emulsifiers and different polyols were all higher than 90% of the added amount. It is believed that the gel system has a significant effect on the stability of the caffeine content, which further indicates that high-concentration encapsulated caffeine can stably exert its efficacy in this system.

[0182] Example 15: Preparation of a gel containing caffeine

[0183] Weigh 9 parts by mass of encapsulated caffeine (4.5 parts by mass of caffeine) and 41.5 parts by mass of 1,3-propylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, as the alcohol phase. Take another beaker and mix 30 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane cross-polymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for standby use.

[0184] Example 16: Preparation of a gel containing caffeine

[0185] Weigh 9 parts by mass of encapsulated caffeine (4.5 parts by mass of caffeine) and 46.5 parts by mass of 1,3-propylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, as the alcohol phase. Take another beaker and mix 25 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane cross-linked polymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine dispersed in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then stand at room temperature for 12 hours for standby.

[0186] Example 17: Preparation of a gel containing caffeine

[0187] Weigh 13 parts by mass of encapsulated caffeine (6.5 parts by mass of caffeine) and 37.5 parts by mass of 1,3-propylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, as the alcohol phase. Take another beaker and mix 30 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane cross-linked polymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for standby.

[0188] Example 18: Preparation of a gel containing caffeine

[0189] Weigh 13 parts by mass of encapsulated caffeine (6.5 parts by mass of caffeine) and 42.5 parts by mass of 1,3-propylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, as the alcohol phase. Take another beaker and mix 25 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane cross-polymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine dispersed in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then stand at room temperature for 12 hours for standby.

[0190] Example 19: Preparation of a gel containing caffeine

[0191] Weigh 15 parts by mass of encapsulated caffeine (7.5 parts by mass of caffeine) and 35.5 parts by mass of 1,3-propylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, as the alcohol phase. Take another beaker and mix 30 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane cross-polymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then let it stand at room temperature for 12 hours for standby use.

[0192] Example 20: Preparation of a gel containing caffeine

[0193] Weigh 15 parts by mass of encapsulated caffeine (7.5 parts by mass of caffeine) and 40.5 parts by mass of 1,3-propylene glycol and homogenize at room temperature at 2500-3000 rpm. Homogenize for 5-6 minutes until there are no particles, as the alcohol phase. Take another beaker and mix 25 parts by mass of polydimethylsiloxane / vinyl polydimethylsiloxane cross-polymer, 10 parts by mass of polydimethylsiloxane, 5 parts by mass of cetearyl alcohol ethylhexanoate and 2 parts by mass of lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, as the oil phase. Slowly drop the polyol solution of caffeine in the oil phase, homogenize at room temperature at 2500-3000 rpm, and homogenize for 5-15 minutes until the alcohol phase is added; add 0.5 parts by mass of phenoxyethanol, add 2 parts by mass of deionized water, and continue to mix and stir at a speed of 100 rpm for 10-20 minutes; then stand at room temperature for 12 hours for standby.

[0194] Test Example 6: Product viscosity test and high and low temperature stability test

[0195] After measuring the viscosity of the systems of Examples 15-20, the high and low temperature stability thereof was investigated.

[0196] Use BROOKFIELD RVDVC digital viscometer (with RV and T-type rotors), sample test temperature: 25℃, constant temperature for 4h, sample test container: try to use the same specification beaker (180ml bottle) when testing different batches of the same sample; reading recording time: 60s for LV / RV type rotors; 90s for T-type rotors; before measuring the sample, make sure there is no bubble interference. Select the corresponding rotor and speed according to the standard. After taking the sample out of the thermostatic bath, immediately measure its viscosity with a rotational viscometer. When selecting LV and RV rotors, insert the rotor obliquely into the sample so that the liquid level is just in the depression of the rotor, and keep the rotor wall free of bubbles; when selecting T-type rotors, make the rotor just close to the liquid surface, and select a certain up and down movement distance so that the rotor has enough up and down space without touching the bottom of the beaker and causing damage. Record the viscosity result after the reading stabilizes (or after the time specified by the standard).

[0197] The high and low temperature stability evaluation method is as follows: Place the aqueous sample prepared in Examples 15-20 in a thermostat stable at high temperature (48°C, 25°C, 4°C) and observe for 30 days. Observe whether the sample has solid precipitation, jelly, stratification, etc. If the sample is normal and unchanged before and after a certain time within 30 days, it means "passed", the appearance of fixed substances means "precipitation", the phenomenon that the material solidifies and is not easy to flow means "jelly", and the phenomenon of two layers of liquid above and below means "stratification". The results are shown in the following table.

[0198] Table 5 shows the stability study and viscosity results for Examples 15-20.

[0199] Table 5

[0200]

[0201] Conclusion: Gels containing caffeine were prepared, and the stability of gels with different caffeine and different dimethicone / vinyl dimethicone cross-linked polymer contents was investigated. The above experimental results show that the stability of gels containing 9-13 parts by mass of encapsulated caffeine (4.5-6.5 parts by mass of caffeine) is good, and the others meet the qualified requirements of consumers for the stability of gel dosage forms. However, in the viscosity test of the gel containing 15 parts by mass of encapsulated caffeine (7.5 parts by mass of caffeine), there is an obvious viscosity reduction phenomenon, and there is a certain stability risk.

[0202] Test Example 7: Caffeine content test of products after high temperature treatment

[0203] Test sample: Caffeine-containing aqueous solution prepared in Examples 15-20 (heated at 48°C for one month)

[0204] (1) Detection instrument: Waters ARC high performance liquid chromatograph with diode array detector, or equivalent model.

[0205] (2) Testing conditions:

[0206] Chromatographic column: Agilent SB-C18 column (250 mm × 4.6 mm, 5 μm, Agilent).

[0207] Mobile phase: acetonitrile: water (pH adjusted to 2.5 with phosphoric acid) = 30:70.

[0208] Detection wavelength: 270nm.

[0209] Flow rate: 1.0 mL / min; injection volume: 10 μL; column temperature: 30°C.

[0210] (3) Standard curve: Weigh 0.1g (accurate to 0.1mg) of raw material-encapsulated caffeine (caffeine content is 50%) into a 50mL volumetric flask, dissolve it in water and make up to volume, shake well, and prepare a standard stock solution. Take 0.1mL, 0.2mL, 0.5mL, 1mL, and 2mL of the above standard stock solution into a 10mL volumetric flask, make up to volume with mobile phase, and prepare standard working solutions with caffeine contents of 10μg / mL, 20μg / mL, 50μg / mL, 100μg / mL, and 200μg / mL, respectively. Perform injection detection according to the above detection conditions (2), draw a standard curve with peak area as the ordinate and caffeine content as the abscissa, and calculate the linear regression equation of the standard curve.

[0211] (4) Sample processing and detection: Take 0.1g of sample (accurate to 0.1mg) in a 50mL stoppered colorimetric tube, add about 40mL of mobile phase, and ultrasonically extract for 20min. Use mobile phase to make up to volume, shake well, and filter part of the liquid through a 0.45μm filter membrane to obtain the test solution. Perform sample injection detection according to the above detection conditions (2), and quantify the sample on the standard curve. The caffeine response value in the sample solution should be within the linear range of the standard curve.

[0212] (5) Calculation formula: external standard method, the calculation formula for caffeine content in the sample is:

[0213]

[0214] Where:

[0215] X——mass fraction of caffeine in the sample, %;

[0216] C——The concentration of caffeine in the test solution obtained from the standard curve, in micrograms per milliliter (μg·mL-1);

[0217] V——total volume of the sample after dilution, in milliliters (mL);

[0218] M——sample mass, in grams (g);

[0219] Table 6 shows the caffeine content of the aqueous solutions of Examples 15-20 after high temperature treatment.

[0220] Table 6

[0221] sample pH Caffeine Content% Recovery rate % Embodiment 15 5.3 4.32 96.00％ Example 16 5.4 4.38 97.33％ Embodiment 17 5.7 6.12 94.15％ Embodiment 18 5.7 6.27 96.46％ Embodiment 19 6 6.82 90.93％ Embodiment 20 6 6.85 91.33％

[0222] Conclusion: A gel containing caffeine was prepared, and the effective caffeine content of gels with different caffeine and different dimethicone / vinyl dimethicone cross-linked polymer contents after high temperature was investigated. Taking into account the test deviation and addition loss, it is generally believed that a recovery rate of more than 90% is the effective concentration of the active substance, and a recovery rate below 90% is considered to have a risk of precipitation or deterioration. After high temperature, the test contents of Examples 15-20 of the gels with different emulsifiers and different polyols were all higher than 90% of the added amount. It is believed that the gel system has a significant effect on the stabilization of the caffeine content, which further indicates that high-concentration encapsulated caffeine can stably exert its efficacy in the system.

Claims

1. A stable high-caffeine composition comprising: 0.1-20% by weight of caffeine; 5-40 wt.% dimethicone / vinyl dimethicone crosspolymer; 2-15 wt% polydimethylsiloxane; 0.01-5 wt% of an emulsifier, wherein the emulsifier is selected from: cetyl PEG / PPG-10 / 1 polydimethylsiloxane, lauryl PEG-9 polydimethylsiloxyethyl polydimethylsiloxane, or a combination thereof; 0.5-10% by weight of cetearyl ethylhexanoate; 5-60 wt% of a polyol selected from propylene glycol, butylene glycol, glycerol, methylpropanediol, or a combination thereof; and water.

2. The composition according to claim 1, characterized in that The composition also comprises 0.01-0.7 wt % of a preservative.

3. The composition according to claim 1, characterized in that The composition comprises 2-6.5% by weight of caffeine.

4. The composition according to claim 1, characterized in that The composition comprises 10-35% by weight of dimethicone / vinyl dimethicone crosspolymer.

5. The composition according to claim 1, characterized in that The composition comprises 5-15% by weight of polydimethylsiloxane.

6. The composition according to claim 1, characterized in that The composition comprises 0.5-5% by weight of an emulsifier.

7. The composition according to claim 1, characterized in that The composition comprises 30-60% by weight of a polyol.

8. The composition according to claim 1, characterized in that The composition is in the form of a gel.

9. The method for preparing the composition according to any one of claims 1 to 8, comprising the following steps: (a) weighing caffeine and polyol, homogenizing and obtaining an alcohol phase; (b) mixing dimethicone / vinyl dimethicone crosspolymer, dimethicone, an emulsifier and cetearyl ethylhexanoate as an oil phase; (c) adding dropwise the alcohol phase of step (a) to the oil phase of step (b) and homogenizing; (d) add water and mix, (e) After standing, the composition of the present invention is obtained.

10. The preparation method according to claim 9, characterized in that: The homogenization in step (a) includes 2500-3000 rpm and homogenization for 5-6 minutes.

11. The preparation method according to claim 9, characterized in that: The homogenization in step (c) includes 2500-3000 rpm and homogenization for 5-15 minutes.

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