Compositions comprising triethanolamine and tranexamic acid modified hydroxytyrosol, methods of making and uses thereof

Abstract

The invention belongs to the technical field of cosmetic preparations, and particularly relates to a composition containing triethanolamine and tranexamic acid modified hydroxytyrosol as well as a preparation method and application of the composition. According to the invention, hydroxytyrosol is modified by using triethanolamine and tranexamic acid through etherification and esterification reactions, the processing mode obviously enhances the electrification capability of hydroxytyrosol, and further obviously enhances the antibacterial strength of hydroxytyrosol, so that hydroxytyrosol is compounded with triethanolamine and tranexamic acid to replace a traditional preservative, and the antibacterial property of hydroxytyrosol is improved. And adverse reactions such as irritation and allergy of common preservatives are improved. According to the invention, the hydroxytyrosol is modified by using triethanolamine and tranexamic acid, and triethanolamine and tranexamic acid are functional components, so that triethanolamine and tranexamic acid can play roles in resisting oxidation, whitening and the like together with hydroxytyrosol in a cosmetic matrix while playing a role in improving the bacteriostasis of hydroxytyrosol.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetic preparations, and particularly relates to a composition comprising triethanolamine and tranexamic acid-modified hydroxytyrosol, a preparation method and uses thereof. Background Art

[0002] Hydroxytyrosol is a plant monomer with rich activity, which is often used in food, cosmetics and health products. Hydroxytyrosol raw materials themselves have a variety of pharmacological effects. For example, it is beneficial to bone growth and function, helps the body absorb minerals, and has the effects of improving the function of the endocrine system, promoting metabolism, promoting wound healing, eliminating free radicals in the body, restoring the health of human organs, preventing brain failure, delaying aging, and maintaining youthful vitality; Hydroxytyrosol can also intervene in lung cancer, breast cancer, uterine cancer, prostate cancer, etc., promote the recovery of cancer in the later stage and improve the effect of chemotherapy; prevent and treat various diseases caused by smoking; and have preventive and therapeutic effects on arteriosclerosis, hypertension, heart disease, cerebral hemorrhage, etc. Hydroxytyrosol is used in cosmetics to effectively enhance skin elasticity and moisturizing, and has antioxidant and anti-wrinkle and anti-aging effects.

[0003] In addition, hydroxytyrosol also has antibacterial, antiviral and antifungal effects, but in fact the antibacterial ability of hydroxytyrosol is not strong, and simple hydroxytyrosol is difficult to achieve the effect of completely inhibiting bacteria, molds and yeasts as a cosmetic preservative. For example, CN111973488A discloses a broad-spectrum antibacterial compatibility skin care product matrix and a preparation method thereof. In this patent document, only the antibacterial characteristics of hydroxytyrosol are utilized, and it is added to the skin care product matrix as an antibacterial agent, which is only a simple use of the antibacterial characteristics of hydroxytyrosol. CN105594704A discloses an antibacterial composition and its application in antibacterial laundry detergent. In this patent document, hydroxytyrosol is utilized to have the antibacterial characteristics, and it is combined with other components that also have antibacterial effects to jointly play an antibacterial effect. However, this patent document simply combines soybean extract, oligomeric chitosan quaternary ammonium salt and olive leaf extract in laundry detergent, because oligomeric chitosan quaternary ammonium salt itself has antibacterial properties, so the simple combination of the two does not have obvious innovation.

[0004] In view of this, it is urgent to develop new methods to enhance the antibacterial activity of hydroxytyrosol. Summary of the invention

[0005] In order to solve the above problems existing in the prior art, the present invention provides a composition comprising triethanolamine and tranexamic acid modified hydroxytyrosol, and a preparation method and use thereof. The present invention uses triethanolamine and tranexamic acid to modify hydroxytyrosol, and while enhancing its antibacterial properties, it is compared with traditional preservatives, in order to reduce the risk of irritation caused by the addition of preservatives in the cosmetic formula system.

[0006] Specifically, the present invention is realized through the following technical solutions:

[0007] In a first aspect, the present invention provides a method for preparing a composition comprising triethanolamine and tranexamic acid-modified hydroxytyrosol, the preparation method comprising the following steps:

[0008] In parts by weight, 0.1-2 parts of hydroxytyrosol, 0.5-5 parts of triethanolamine and 0.5-5 parts of tranexamic acid are reacted in 5-20 parts of water at a reaction temperature of 40-80° C. for a reaction time of 0.5-1.5 hours.

[0009] As an optional mode, in the above preparation method, the preparation method comprises the following steps:

[0010] In parts by weight, 0.5-1.5 parts of hydroxytyrosol are reacted with 2-4 parts of triethanolamine and 2-4 parts of tranexamic acid in 5-15 parts of water at a reaction temperature of 50-70° C. for a reaction time of 0.8-1 h.

[0011] As an optional mode, in the above preparation method, the preparation method comprises the following steps:

[0012] In parts by weight, 1 part of hydroxytyrosol is reacted with 3 parts of triethanolamine and 3 parts of tranexamic acid in 5-15 parts of water at a reaction temperature of 60° C. for 1 hour.

[0013] As an optional mode, in the above preparation method, in the preparation method, one or more of the following three types of reactions occur during the reaction process, so that triethanolamine, tranexamic acid and hydroxytyrosol react with each other, thereby enhancing the charge between them,

[0014] (1) Hydroxytyrosol and triethanolamine undergo etherification reaction, so that triethanolamine carries active electrons, which enhances the charge of hydroxytyrosol;

[0015]

[0016] (2) Hydroxytyrosol and tranexamic acid undergo an esterification reaction, which allows tranexamic acid to carry active electrons, thereby enhancing the charge of hydroxytyrosol;

[0017]

[0018] (3) triethanolamine and tranexamic acid undergo etherification reaction, which enhances their respective charge properties;

[0020]

[0021] In a second aspect, the present invention provides a composition prepared by the preparation method described in the first aspect.

[0022] As an option, in the above composition, the charge of hydroxytyrosol is increased.

[0023] As an optional mode, in the above composition, the composition has antibacterial, whitening and antioxidant effects.

[0024] As an optional mode, in the above composition, the antibacterial effect of the composition is significantly better than that of hydroxytyrosol used alone in the same amount.

[0025] In a third aspect, the present invention provides use of the composition of the second aspect in preparing cosmetics.

[0026] In a fourth aspect, the present invention provides use of the composition described in the second aspect in preparing a cosmetic preservative.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] (1) The present invention uses triethanolamine and tranexamic acid to modify hydroxytyrosol through etherification and esterification reactions. This treatment method significantly enhances the charging ability of hydroxytyrosol, thereby significantly enhancing the antibacterial strength of hydroxytyrosol. Therefore, the use of hydroxytyrosol combined with triethanolamine and tranexamic acid can replace traditional preservatives to improve the adverse reactions of ordinary preservatives such as irritation and allergies.

[0029] (2) The present invention uses triethanolamine and tranexamic acid to modify hydroxytyrosol. While improving the antibacterial effect of hydroxytyrosol, since triethanolamine and tranexamic acid are themselves effective ingredients, they can also play antioxidant and whitening effects together with hydroxytyrosol in the cosmetic matrix. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 :Photo of the experimental results of hydroxytyrosol antibacterial activity and total colony count. The left culture dish is sample one, the middle culture dish is sample two, and the right culture dish is sample three.

[0031] Figure 2 : Photo of the total bacterial count test results of the modified hydroxytyrosol and unmodified hydroxytyrosol. The left culture dish is sample one, the middle culture dish is sample two, and the right culture dish is sample three.

[0032] Figure 3 : Photo of the total bacterial count test results of the antibacterial activity comparison between modified hydroxytyrosol and phenoxyethanol. The left culture dish is sample one, the middle culture dish is sample two, and the right culture dish is sample three. DETAILED DESCRIPTION

[0033] In the above summary of the invention and the specific embodiments, as well as in the claims, specific features of the present invention are mentioned, and it should be understood that all possible combinations including these specific features are disclosed in the specification of the present invention. For example, when a specific feature is disclosed in a specific aspect or embodiment of the present invention or a specific claim, the feature may also be used as much as possible and / or in combination with other specific aspects and embodiments of the present invention.

[0034] The present invention will be further described with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0035] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0036] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0037] Example:

[0038] Example 1: Comparison of antibacterial activity of hydroxytyrosol

[0039] Including hydroxytyrosol, phenoxyethanol, ethylhexylglycerin, etc., the higher the content, the stronger the antibacterial effect. Therefore, this embodiment selects an addition amount of 0.1% by mass, and compares the antibacterial effects of different raw materials in the same formula matrix in parallel, with the total colony count experimental data as the comparison.

[0040] The cosmetic matrix samples were prepared. Except for hydroxytyrosol, phenoxyethanol and ethylhexylglycerin, other matrix raw materials remained the same. See Table 1 for details.

[0041] Table 1: Hydroxytyrosol antibacterial comparison test formula

[0042] Recipe Sheet Sample 1 / g Sample 2 / g Sample 3 / g Hydroxytyrosol 0.1 0 0 Phenoxyethanol 0 0.1 0 Ethylhexylglycerin 0 0 0.1 collagen 1 1 1 glucose 1 1 1 Panthenol 1 1 1 water Up to 100 Up to 100 Up to 100

[0043] The total colony count test procedure is as follows: Use a sterile pipette to draw 2 mL of the 1:10 diluted test solution and inject it into two sterile plates, 1 mL per plate. Take another 1 mL and inject it into a 9 mL sterile saline test tube (be careful not to let the pipette touch the liquid surface), replace a pipette, and mix thoroughly to make a 1:100 test solution. Draw 2 mL and inject it into two sterile plates, 1 mL per plate. Pour the melted and cooled lecithin Tween 80 nutrient agar medium to 45℃-50℃ into the plate, about 15 mL per plate, and then rotate the plate to mix the sample and the medium thoroughly. After the agar solidifies, turn the plate over and place it in a 36℃±1℃ incubator for 48h±2h. Take another sterilized empty plate without sample, add about 15mL of lecithin Tween 80 nutrient agar medium, wait for the agar to solidify, turn the plate over, and place it in a 36℃±1℃ incubator for 48h±2h as a blank control. To distinguish the particles and colonies in cosmetics, add 1mL of 0.5% triphenyltetrazolium chloride (TTC) solution to every 100mL of lecithin Tween 80 nutrient agar. If bacteria are present, the colonies will be red after incubation, while the color of the cosmetic particles will not change.

[0044] like Figure 1 As shown, the results show that sample 1 is too many to count; sample 2 is 1 CFU / mL; sample 3 is 12 CFU / mL. From the total colony count experimental data, it can be seen that 0.1% phenoxyethanol can effectively achieve the antibacterial effect and there is still room for improvement, while 0.1% hydroxytyrosol and ethylhexylglycerin cannot play an effective antibacterial role.

[0045] Example 2: Modification reaction of hydroxytyrosol with triethanolamine and tranexamic acid

[0046] Experimental plan: In terms of weight, 1 part of hydroxytyrosol is reacted with 3 parts of triethanolamine and 3 parts of tranexamic acid in 10 parts of water. The reaction temperature is 60°C and the reaction time is 1 hour. During the reaction, one or more of the following three types of reactions occur, causing triethanolamine, tranexamic acid and hydroxytyrosol to react with each other, thereby enhancing the charge between them.

[0047] 1. Hydroxytyrosol and triethanolamine undergo etherification reaction, so that triethanolamine carries active electrons, which enhances the charge of hydroxytyrosol;

[0048]

[0049] 2. Hydroxytyrosol and tranexamic acid undergo an esterification reaction, which allows tranexamic acid to carry active electrons, thereby enhancing the charge of hydroxytyrosol;

[0050]

[0051] 3. The etherification reaction between triethanolamine and tranexamic acid enhances the charge of each other;

[0052]

[0053] In order to verify the charge status of hydroxytyrosol modified by triethanolamine and tranexamic acid, the following four groups of samples were tested for conductivity using a conductivity meter. The results are shown in Table 2 below.

[0054] Table 2: Conductivity of hydroxytyrosol modified with triethanolamine and tranexamic acid

[0055] Dissolve in 10 g of water Conductivity / mS 1g hydroxytyrosol + 3g triethanolamine + 3g tranexamic acid 0.72 1g hydroxytyrosol + 3g triethanolamine 0.6 1g Hydroxytyrosol + 3g Tranexamic Acid 0.33 3g triethanolamine + 3g tranexamic acid 0.59 1 g hydroxytyrosol 0.36 3 g triethanolamine 0.62 3 g Tranexamic Acid 0.39

[0056] The antibacterial mechanism of hydroxytyrosol is not very clear yet. It is speculated that it may be preferentially adsorbed to the surface of negatively charged bacteria through electrostatic adsorption between charges, wrapping the bacteria as a whole, forming a layer of ion groups of different concentrations on the surface of the bacteria, destroying the original permeability of the cell wall, thereby destroying the bacterial protoplasm membrane, and then destroying the permeability of the cell membrane, causing the cells to die quickly. From the conductivity data, it can be seen that the charge of the modified hydroxytyrosol complex solution is significantly improved compared with the unmodified hydroxytyrosol solution.

[0057] Example 3: Antibacterial Comparison Experiment of Modified Hydroxytyrosol and Unmodified Hydroxytyrosol

[0058] The cosmetic matrix samples were prepared. Except for the differences in hydroxytyrosol, triethanolamine and tranexamic acid, the other matrix raw materials remained the same. Samples 1, 2 and 3 were all treated at a reaction temperature of 60°C and a reaction time of 1 h. See Table 3 below for details.

[0059] Table 3: Antibacterial comparison experimental formula of modified hydroxytyrosol and unmodified hydroxytyrosol

[0060]

[0061]

[0062] The total colony count test procedure is as follows: Use a sterile pipette to draw 2 mL of the 1:10 diluted test solution and inject it into two sterile plates, 1 mL per plate. Take another 1 mL and inject it into a 9 mL sterile saline test tube (be careful not to let the pipette touch the liquid surface), replace a pipette, and mix thoroughly to make a 1:100 test solution. Draw 2 mL and inject it into two sterile plates, 1 mL per plate. Pour the melted and cooled lecithin Tween 80 nutrient agar medium to 45℃-50℃ into the plate, about 15 mL per plate, and then rotate the plate to mix the sample and the medium thoroughly. After the agar solidifies, turn the plate over and place it in a 36℃±1℃ incubator for 48h±2h. Take another sterilized empty plate without sample, add about 15mL of lecithin Tween 80 nutrient agar medium, wait for the agar to solidify, turn the plate over, and place it in a 36℃±1℃ incubator for 48h±2h as a blank control. To distinguish the particles and colonies in cosmetics, add 1mL of 0.5% triphenyltetrazolium chloride (TTC) solution to every 100mL of lecithin Tween 80 nutrient agar. If bacteria are present, the colonies will be red after incubation, while the color of the cosmetic particles will not change.

[0063] like Figure 2 As shown, the results show that sample 1 has too many colonies to count; sample 2 has no colonies; and sample 3 has too many colonies to count. From the total colony count experimental data, it can be seen that only hydroxytyrosol combined with triethanolamine and tranexamic acid (that is, hydroxytyrosol modified with triethanolamine and tranexamic acid) can exert a significant antibacterial effect, while unmodified hydroxytyrosol has obviously insufficient antibacterial activity, and hydroxytyrosol containing only tranexamic acid and triethanolamine has no antibacterial activity.

[0064] Example 4: Comparative experiment on antibacterial activity of modified hydroxytyrosol and phenoxyethanol

[0065] The cosmetic matrix samples were prepared. Except for the differences in hydroxytyrosol, triethanolamine, tranexamic acid, and phenoxyethanol, the other matrix raw materials remained the same. Sample 1 was treated at a reaction temperature of 60°C and a reaction time of 1 h. Samples 2 and 3 did not need to be treated in this way. See Table 4 below for details.

[0066] Table 4: Comparative experimental formula of antibacterial activity of modified hydroxytyrosol and phenoxyethanol

[0067]

[0068]

[0069] The total colony count test procedure is as follows: Use a sterile pipette to draw 2 mL of the 1:10 diluted test solution and inject it into two sterile plates, 1 mL per plate. Take another 1 mL and inject it into a 9 mL sterile saline test tube (be careful not to let the pipette touch the liquid surface), replace a pipette, and mix thoroughly to make a 1:100 test solution. Draw 2 mL and inject it into two sterile plates, 1 mL per plate. Pour the melted and cooled lecithin Tween 80 nutrient agar medium to 45℃-50℃ into the plate, about 15 mL per plate, and then rotate the plate to mix the sample and the medium thoroughly. After the agar solidifies, turn the plate over and place it in a 36℃±1℃ incubator for 48h±2h. Take another sterilized empty plate without sample, add about 15mL of lecithin Tween 80 nutrient agar medium, wait for the agar to solidify, turn the plate over, and place it in a 36℃±1℃ incubator for 48h±2h as a blank control. To distinguish the particles and colonies in cosmetics, add 1mL of 0.5% triphenyltetrazolium chloride (TTC) solution to every 100mL of lecithin Tween 80 nutrient agar. If bacteria are present, the colonies will be red after incubation, while the color of the cosmetic particles will not change.

[0070] like Figure 3 As shown, the results show that sample 1 has no colonies; sample 2 has 4 CFU / mL; sample 3 has no colonies. From the total colony count experimental data, it can be seen that hydroxytyrosol combined with triethanolamine and tranexamic acid has a significant antibacterial effect, and increasing the content of phenoxyethanol can significantly improve its antibacterial effect. From the experimental results, 0.1% hydroxytyrosol combined with triethanolamine and tranexamic acid can be equivalent to the antibacterial strength of 0.3% phenoxyethanol.

[0071] Example 5: Preparation of cosmetics using modified hydroxytyrosol as a preservative

[0072] The cosmetic matrix prepared according to the formula in Table 5 below was tested for thermotolerant coliform bacteria, Pseudomonas aeruginosa, Staphylococcus aureus, molds and yeasts. The sample was treated at a reaction temperature of 60° C. and a reaction time of 1 h.

[0073] Table 5: Formula of cosmetics prepared with modified hydroxytyrosol as preservative

[0074]

[0075]

[0076] 1. Thermotolerant coliform bacteria

[0077] 1.1 Thermotolerant coliform bacteria are a group of aerobic and anaerobic Gram-negative non-spore-forming bacilli that can ferment lactose to produce acid and gas when cultured at 44.5℃ for 24-48 hours. The bacteria mainly come from human and warm-blooded animal feces and can be used as a fecal contamination indicator to evaluate the hygienic quality of cosmetics and infer whether there is a possibility of intestinal pathogens in cosmetics.

[0078] 1.2 Operation steps: Take 1 mL of the sample solution of Example 5 and add it to 9 mL of double lactose bile salt (containing neutralizer) culture medium, and culture it in a 44.5°C±0.5°C incubator for 24 hours. If neither acid nor gas is produced, continue to culture for 48 hours. If still neither acid nor gas is produced, report it as negative for thermotolerant coliform group.

[0079] 1.3 The test results are negative.

[0080] 2. Pseudomonas aeruginosa test method

[0081] 2.1 Pseudomonas aeruginosa belongs to the genus Pseudomonas, is a Gram-negative bacillus, is oxidase-positive, and can produce pyocyanin. In addition, it can liquefy gelatin, reduce nitrate to nitrite, and grow at 42℃±1℃.

[0082] 2.2 Operation steps:

[0083] Bacterial enrichment culture: Take 1 mL of the original solution of Example 5 and add it to 9 mL of SCDLP liquid culture medium, and culture it at 36°C±1°C for 18h-24h. If Pseudomonas aeruginosa grows, there will be a thin bacterial film on the surface of the culture medium, and the culture medium is usually yellow-green or blue-green.

[0084] 42℃ growth test: Pick out suspected pure culture of Pseudomonas aeruginosa, inoculate it on ordinary agar slant culture medium, place it in an incubator at 42℃±1℃, and culture it for 24h-48h. Pseudomonas aeruginosa can grow and is positive, while the similar fluorescent Pseudomonas cannot grow.

[0085] 2.3 The experimental results are negative.

[0086] 3. Staphylococcus aureus test

[0087] 3.1 Staphylococcus aureus is a Gram-positive coccus, arranged in grape-like shapes, without spores or capsules, capable of decomposing mannitol, and with positive plasma coagulase.

[0088] 3.2 Bacterial enrichment: Take 1 mL of the sample in Example 5 and inoculate it into 9 mL of SCDLP liquid culture medium, place it in an incubator at 36°C±1°C, and culture it for 24h±2h.

[0089] 3.3 The experimental results are negative.

[0090] 4. Mold and Yeast

[0091] 4.1 Experimental operation steps: Take 1mL of the original solution of the sample of Example 5 and inject it into a sterilized plate. Use 2 plates for each sample, inject the red bengal medium that has been melted and cooled to about 45℃±1℃, and shake it thoroughly. After solidification, turn the plate over, incubate at 28℃±2℃ for 5 days, observe and record. Take another sterilized empty plate without sample, add about 15mL of red bengal medium, wait for the agar to solidify, turn the plate over, and incubate at 28℃±2℃ incubator for 5 days, which is a blank control.

[0092] 4.2 The test results are negative.

[0093] Combined with the experimental data of Example 4, hydroxytyrosol combined with triethanolamine and tranexamic acid can play a preservative role, and the microbial detection results of the cosmetic matrix containing hydroxytyrosol, triethanolamine and tranexamic acid were all negative.

[0094] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A method for preparing a composition comprising triethanolamine and tranexamic acid-modified hydroxytyrosol, characterized in that: The preparation method comprises the following steps: In parts by weight, 0.1-2 parts of hydroxytyrosol, 0.5-5 parts of triethanolamine and 0.5-5 parts of tranexamic acid are reacted in 5-20 parts of water at a reaction temperature of 40-80° C. for a reaction time of 0.5-1.5 hours.

2. The preparation method according to claim 1, characterized in that: The preparation method comprises the following steps: In parts by weight, 0.5-1.5 parts of hydroxytyrosol are reacted with 2-4 parts of triethanolamine and 2-4 parts of tranexamic acid in 5-15 parts of water at a reaction temperature of 50-70° C. for a reaction time of 0.8-1 h.

3. The preparation method according to claim 1, characterized in that: In the preparation method, one or more of the following three types of reactions occur during the reaction process, so that triethanolamine, tranexamic acid and hydroxytyrosol react with each other, thereby enhancing the charge between them. (1) Hydroxytyrosol and triethanolamine undergo etherification reaction, so that triethanolamine carries active electrons, which enhances the charge of hydroxytyrosol; (2) Hydroxytyrosol and tranexamic acid undergo an esterification reaction, which allows tranexamic acid to carry active electrons, thereby enhancing the charge of hydroxytyrosol; or (3) triethanolamine and tranexamic acid undergo etherification reaction, which enhances the charge of each; 4. A composition prepared by the preparation method according to any one of claims 1 to 3.

5. The composition according to claim 4, characterized in that: In the composition, the charge of hydroxytyrosol is increased.

6. The composition according to claim 4, characterized in that: In the composition, the composition has antibacterial, whitening and antioxidant effects.

7. The composition according to claim 4, characterized in that: In the composition, the antibacterial effect of the composition is significantly better than that of hydroxytyrosol used alone in the same amount.

8. Use of the composition according to any one of claims 4 to 7 in the preparation of cosmetics.

9. Use of the composition according to any one of claims 4 to 7 in the preparation of a cosmetic preservative.

Images