Application of patchouli ketone in the preparation of anti-caries oral care agent

Abstract

The present invention discloses the application of patchouli ketone in the preparation of an anti-caries oral care agent. Specifically disclosed is an anti-caries oral care agent containing patchouli ketone. The present invention unexpectedly finds that patchouli ketone has significant anti-streptococcus mutans activity, which is of great significance for preventing the formation of dental plaque. Mutans streptococcus is one of the main pathogens that cause dental caries in the oral cavity. It can effectively inhibit the growth and reproduction of the bacteria, showing the great potential of patchouli ketone in oral health maintenance. Further studies have shown that patchouli ketone can not only be used alone as an effective ingredient for anti-caries oral care, but also can be used in combination with other oral care ingredients to synergistically enhance the anti-caries effect. This compounding strategy not only broadens its scope of application, but also optimizes the overall performance of oral care products and improves user experience. The use of an anti-caries oral care agent containing patchouli ketone can achieve long-term inhibition of the formation of dental plaque and dental caries while achieving antibacterial and anti-inflammatory effects.

Description

Technical Field

[0001] The invention relates to the technical field of oral care products, and in particular to application of patchouli ketone in the preparation of an anti-caries oral care agent. Background Art

[0002] Dental caries, as a prevalent oral disease worldwide, not only affects an individual's chewing function and oral aesthetics, but can also cause severe pain, infection, and even trigger a series of systemic diseases, such as cardiovascular disease and worsening of diabetic complications, which seriously endangers human health.

[0003] Traditional methods of preventing dental caries, such as using fluoride toothpaste, can effectively prevent dental caries to a certain extent, but long-term and excessive use may bring health risks such as dental fluorosis and skeletal fluorosis, especially for children, and its safety is of particular concern. At the same time, with the deepening of microbiological research, people have realized that the formation of dental caries is a complex biological process involving multiple levels such as oral microecological balance, bacterial metabolism, and enamel structure. It is difficult to meet the needs of comprehensive dental caries prevention by relying solely on fluoride.

[0004] Therefore, it is of great significance to develop new anti-caries oral care products to achieve more accurate, safe and efficient anti-caries strategies. This type of toothpaste may contain but is not limited to: natural antibacterial ingredients: such as broad-spectrum antibacterial active substances extracted from plants, which can not only effectively inhibit the growth of cariogenic bacteria such as Streptococcus mutans, but also maintain the balance of oral microecology and reduce side effects. Bioactive materials: such as calcium-phosphorus compounds, bioglass, etc., which can form a protective layer on the surface of teeth, promote the remineralization of enamel, and enhance the ability of teeth to resist acid erosion. Intelligent sustained-release technology: by designing an intelligent release system, the active ingredients in toothpaste are continuously and slowly released in the mouth, prolonging its action time and improving the anti-caries effect. Oral microenvironment regulator: by adjusting microenvironmental parameters such as oral pH and redox state, conditions that are not conducive to the survival of cariogenic bacteria are created to fundamentally prevent the occurrence of caries.

[0005] In summary, the preparation of a new type of anti-caries toothpaste that combines safety, efficiency and comprehensive protection is an important technical approach to meet the current oral health challenges and improve the oral health level of the whole people. This not only requires researchers to have a deep understanding of the biological mechanism of caries, but also requires continuous innovation of materials and technologies to meet the growing demand for oral health. Summary of the invention

[0006] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention proposes the use of patchouli ketone in the preparation of an anti-caries oral care agent, and the anti-caries oral care agent added with patchouli ketone can achieve safe, efficient and comprehensive protection.

[0007] The present invention also provides an anti-caries oral care agent, which can inhibit the generation of dental plaque and caries in a long-term manner while having antibacterial and anti-inflammatory effects.

[0008] The present invention also provides an application of the anti-caries oral care agent.

[0009] Use of patchouli ketone according to the first aspect of the present invention in the preparation of an anti-caries oral care agent.

[0010] According to the application of the embodiment of the present invention, at least the following beneficial effects are achieved: the scheme of the present invention unexpectedly discovered during the research process that patchouli ketone has significant anti-Streptococcus mutans activity, and this discovery is of great significance for preventing the formation of dental plaque. Mutans Streptococcus is one of the main pathogens that cause dental caries in the oral cavity. It can effectively inhibit the growth and reproduction of the bacteria, showing the great potential of patchouli ketone in oral health maintenance. Further studies have shown that patchouli ketone can not only be used alone as an effective ingredient for anti-caries oral care, but can also be used in combination with other oral care ingredients to synergistically enhance the anti-caries effect. This compounding strategy not only broadens its scope of application, but also optimizes the overall performance of oral care products and improves user experience. The use of an anti-caries oral care agent containing patchouli ketone can achieve long-term inhibition of the formation of dental plaque and dental caries while achieving antibacterial and anti-inflammatory effects.

[0011] Based on these unique advantages of patchouli ketone, the oral care solution proposed in the present invention has shown good application effects in preventing caries and reducing dental plaque formation. This innovation not only provides new ideas for the development of oral health products, but also indicates that it has broad application prospects in the oral care industry. Patchouli ketone, as a key active ingredient extracted from patchouli volatile oil, is an important material basis for the efficacy of patchouli. Extensive pharmacological studies at home and abroad have shown that patchouli ketone has a variety of pharmacological activities, including but not limited to anti-inflammatory, antibacterial, antioxidant, antiviral, anti-tumor, gastric protection, brain protection, immunomodulation and insecticide, etc. These characteristics make it have huge market application potential in the pharmaceutical, food and health care products industries. Patchouli ketone has received widespread attention from the academic community due to its excellent antibacterial and antiviral microbial activity. Its antibacterial mechanism includes regulating the interaction of Staphylococcus aureus cell membrane proteins and changing the cell membrane permeability, thereby effectively inhibiting the growth of Staphylococcus aureus; in addition, patchouli ketone can also promote the regression of catarrhal Staphylococcus infection. Through in vitro and in vivo experiments, it was further confirmed that patchouli ketone showed good inhibitory activity against Candida albicans, especially against all fluconazole-resistant Candida albicans. However, despite the wide biological activity and application prospects of patchouli ketone, there has been no research and practice on its application in oral care for bacterial diseases such as dental caries, or its development into anti-caries oral care products.

[0012] The anti-caries oral care agent according to the second embodiment of the present invention comprises an anti-caries component I and an anti-caries component II, wherein the anti-caries component I is patchouli ketone, and the anti-caries component II comprises at least one of magnolol, citral or bornyl acetate.

[0013] The anti-caries oral care agent according to the embodiment of the present invention has at least the following beneficial effects: the present invention unexpectedly found that effectively combining patchouli ketone with one or more of magnolol, citral, bornyl acetate, etc. and applying them to oral products can produce significant synergistic effects, forming a highly effective antibacterial and anti-caries composition component. Specifically, the composition can not only effectively remove the growth of harmful bacteria, thereby reducing the formation of dental plaque and preventing the occurrence of caries, but also show multiple effects of reducing oral inflammation and promoting oral health. This discovery is of great significance for improving the cleaning effect and protective ability of oral products, and provides users with a more comprehensive and safe oral care solution.

[0014] According to some embodiments of the invention, the anti-caries oral care agent further comprises at least one of β-caryophyllene or ethyl p-methoxycinnamate.

[0015] According to some embodiments of the present invention, the anti-caries oral care agent further includes β-caryophyllene and ethyl p-methoxycinnamate; the anti-caries component II includes magnolol, citral and bornyl acetate. The anti-caries oral care agent of the present invention exhibits comprehensive oral health protection properties and exerts significant effects through multiple mechanisms. The compounding of the components in the anti-caries oral care agent of the present invention significantly reduces the formation of dental plaque and the accumulation of acidic products, thereby protecting teeth from corrosion. At the same time, it also has antibacterial and anti-inflammatory functions, can fight other harmful bacteria in the oral cavity, reduce gingival inflammation, and promote the healthy recovery of oral tissues. This feature not only helps to prevent caries, but also shows potential in the treatment of oral infectious diseases such as periodontal disease.

[0016] According to some embodiments of the present invention, the anti-caries oral care agent further comprises β-caryophyllene and ethyl p-methoxycinnamate; and the anti-caries ingredient II comprises magnolol, citral and bornyl acetate.

[0017] According to some embodiments of the present invention, the weight percentage of patchouli ketone in the anti-caries oral care agent is 6% to 99.9%.

[0018] According to some embodiments of the present invention, the patchouli ketone is derived from chemical synthesis or natural product extraction.

[0019] According to some embodiments of the present invention, the magnolol, citral, ethyl p-methoxycinnamate, bornyl acetate, and β-caryophyllene are derived from chemical synthesis or natural product extraction.

[0020] According to the application of the third aspect of the embodiment of the present invention, there is provided an oral care product comprising a base material and the above-mentioned anti-caries oral care agent.

[0021] According to the application of the embodiment of the present invention, at least the following beneficial effects are achieved: the application scope of the anti-caries oral care agent of the present invention is not limited to traditional toothpaste, but can be flexibly expanded to a series of oral care products such as tooth powder, liquid toothpaste, mouthwash, tooth paste, chewing gum, oral freshening spray and tooth care gel. When preparing these diverse products, it is only necessary to follow the standard process of the prior art, and scientifically integrate the specific mixture of patchouli ketone (used alone or in combination), magnolol, citral or bornyl acetate into the respective basic formulas. This innovative formula gives oral care products significant anti-caries performance, indicating that it has a wide range of application potential in the industrial field.

[0022] According to some embodiments of the present invention, the oral care product comprises at least one of toothpaste, tooth powder, liquid toothpaste, mouthwash, tooth paste, chewing gum, oral spray or tooth gel.

[0023] According to some embodiments of the present invention, the oral care product is toothpaste, and the base material comprises a moisturizer, an abrasive, a thickener, a foaming agent, a sweetener, a flavor and a preservative.

[0024] According to some embodiments of the invention, the humectant comprises at least one of glycerol, propylene glycol, diethylene glycol, sorbitol or polyethylene glycol.

[0025] According to some embodiments of the invention, the abrasive comprises at least one of calcium carbonate, hydrated silica, silicon dioxide, calcium pyrophosphate or hydroxyapatite.

[0026] According to some embodiments of the present invention, the thickener includes at least one of sodium carboxymethyl cellulose, xanthan gum, carrageenan, nonionic guar gum, sodium alginate, hydroxyethyl cellulose or carbomer.

[0027] According to some embodiments of the invention, the foaming agent includes at least one of sodium lauryl sulfate, sodium lauroyl sarcosinate, sodium lauryl sulfoacetate or cocopropyl betaine.

[0028] According to some embodiments of the invention, the sweetener comprises at least one of saccharin sodium, monk fruit extract, xylitol or glycerol.

[0029] According to some embodiments of the invention, the flavor comprises at least one of menthol, peppermint oil, spearmint or cardamom.

[0030] According to some embodiments of the invention, the preservative comprises at least one of ethylparaben, propylparaben or sodium benzoate.

[0031] According to some embodiments of the present invention, the toothpaste comprises the following raw materials in parts by weight:

[0032] Anti-caries oral care agent 0.0025-3.566 parts

[0033] 70-90 parts of base material.

[0034] According to some embodiments of the present invention, the toothpaste comprises the following raw materials in parts by weight: 0.0025-0.04 parts of patchouli ketone, 0.000310-0.006 parts of magnolol, 0.0025-0.16 parts of citral, 0.0025-0.16 parts of ethyl p-methoxycinnamate, 0.04-2.56 parts of borneol acetate, 0.01-0.64 parts of β-caryophyllene, and 70-90 parts of base material.

[0035] According to some embodiments of the present invention, the base material includes 10-70 parts of moisturizer, 20-60 parts of abrasive, 0.1-10 parts of thickener, 0.1-10 parts of foaming agent, 0.1-2 parts of sweetener, 0.1-5 parts of flavor, and 0.1-1 part of preservative.

[0036] According to some embodiments of the present invention, the raw materials of the toothpaste further include water, and the total mass of the raw materials is 100 parts, with water being the balance.

[0037] According to the application of the third aspect of the present invention, there is also provided a method for preparing an oral care toothpaste, comprising the following steps:

[0038] S1, dispersing the thickener in the humectant to form a mixed solution A after swelling;

[0039] S2, adding part of water to the above-mentioned anti-caries oral care agent to form a mixed solution B;

[0040] S3, adding a sweetener, a preservative and the remaining water to the mixed solution A to obtain a mixed solution C;

[0041] S4, mixing the mixed solution C with the mixed solution B to form a mixed material D, and then aging it;

[0042] S5, adding a friction agent to the mixture D and mixing to obtain a mixture E;

[0043] S6, adding a foaming agent to the mixed material E and mixing the mixture to obtain a mixed material F;

[0044] S7. Add essence to the mixture F to obtain the oral care toothpaste.

[0045] In the toothpaste preparation process provided by the present invention, the first step is to cause the thickener and the humectant to be thoroughly dispersed and swelled to build a stable basic structure for the toothpaste. Next, the anti-caries oral care agent is dissolved in water after thorough mixing, which significantly enhances its effectiveness in preventing caries and inhibiting bacterial growth. Subsequently, other required ingredients are added to the above mixture. The entire preparation process is carefully designed to ensure the stability of the toothpaste while maximizing the release of the efficacy of patchouli ketone and other active ingredients.

[0046] According to some embodiments of the present invention, the mass fraction of the anti-caries oral care agent in the mixed solution B is 5% to 15%.

[0047] In addition to toothpaste, for other oral care products such as tooth powder, liquid toothpaste, mouthwash, tooth stickers, chewing gum, oral spray, tooth gel, etc., the combination of patchouli ketone and magnolol can be added to the corresponding products according to conventional means in the prior art.

[0048] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The present invention will be further described below with reference to the accompanying drawings and embodiments, wherein:

[0050] Figure 1 This is a schematic diagram of the effect of patchouli ketone, a raw material used in an embodiment of the present invention, on the growth curve of Streptococcus mutans. DETAILED DESCRIPTION

[0051] The following will be combined with the embodiments to clearly and completely describe the concept of the present invention and the technical effects produced, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of them. Based on the embodiments of the present invention, other embodiments obtained by technicians in this field without creative work are all within the scope of protection of the present invention. The test methods used in the embodiments are conventional methods unless otherwise specified; the materials, reagents, etc. used, unless otherwise specified, can be reagents and materials obtained from commercial channels. Unless otherwise specified, the same parameter in each embodiment has the same value. The embodiments described below are exemplary and are only used to explain the present invention, and cannot be understood as limitations on the present invention.

[0052] In the description of the present invention, the description with reference to the term "some embodiments" or the like means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0053] In the description of the present invention, if there is a description of first, second, etc., it is only for the purpose of distinguishing technical features, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features or implicitly indicating the order of the indicated technical features.

[0054] The "room temperature" referred to in the present invention refers to 25±5°C, and is specifically 25°C in the embodiments.

[0055] Patchouli ketone and magnolol, citral, ethyl p-methoxycinnamate, bornyl acetate, and β-caryophyllene can be purchased through commercial means. The patchouli ketone, magnolol, citral, and bornyl acetate used in the embodiments of the present invention are purchased from Shanghai Yuanye Biotechnology Co., Ltd.; ethyl p-methoxycinnamate and β-caryophyllene are extracted by essential oil extraction methods such as steam distillation and supercritical carbon dioxide fluid extraction to obtain essential oils, and then the monomer compounds are precipitated by crystallization.

[0056] Ethyl p-methoxycinnamate is obtained by crystallization of Kaempferia galanga essential oil extracted by supercritical carbon dioxide. The extraction conditions of Kaempferia galanga essential oil are as follows: the pressure of the extraction kettle is 22MPa, the temperature of the extraction kettle is 55℃, and the extraction time is 2h. Other extraction conditions are as follows: the pressure of the separation kettle is 6MPa, the temperature is 40℃ and 30℃ respectively, and the CO2 flow rate is 30kg / h. After the essential oil is left to stand, a crystal precipitate is produced. The crystal is compared with the standard product by liquid chromatography / gas chromatography. The crystal is ethyl p-methoxycinnamate with a purity of ≥95%.

[0057] β-Caryophyllene is derived from the crystallization of the essential oil of the spice Osmanthus fragrans extracted by steam distillation. The extraction method of Osmanthus fragrans is the commonly used steam distillation method in the laboratory, with a solid-liquid ratio of 1:5 to 1:10. The extracted essential oil is allowed to stand to produce crystals. The crystals are compared with the standard using a liquid chromatograph / gas chromatograph, and the crystals are β-caryophyllene with a purity ≥95%.

[0058] The purity of patchouli ketone, magnolol and citral is ≥99.8%, the purity of borneol acetate is ≥99.5%, and purified water is used.

[0059] Example 1

[0060] This example provides the use of patchouli ketone in the preparation of an anti-caries oral care agent.

[0061] This example also provides the use of the anti-caries oral care agent obtained by the above operation in the preparation of toothpaste, and the raw materials for the preparation also include abrasives, thickeners, moisturizers, sweeteners, foaming agents, preservatives, flavors and water. The weight percentages of each raw material are: 0.0025 parts of anti-caries oral care agent (i.e. patchouli ketone), 60 parts of moisturizer (composed of glycerin and sorbitol, the mass ratio of the two is 1:2), 22 parts of abrasives (specifically hydrated silica), 1 part of thickener (composed of xanthan gum and sodium carboxymethyl cellulose, the mass ratio of the two is 4:1), 2 parts of foaming agent (specifically cocoyl propyl betaine), 0.35 parts of sweetener (specifically xylitol), 1 part of flavor (specifically menthol), 0.15 parts of preservative (specifically sodium benzoate), the total mass percentage of raw materials is 100 parts, and water is the balance.

[0062] Specifically, the preparation process is as follows:

[0063] S1: Disperse the thickener evenly in the moisturizer and form a mixed solution A after fully swelling;

[0064] S2: dissolving the anti-caries oral care agent with an appropriate amount of water to form a mixed solution B with a mass fraction of 5%-15%;

[0065] S3: adding a sweetener, a preservative and an appropriate amount of water to the mixed solution A, and stirring evenly to obtain a mixed solution C;

[0066] S4: After the mixed solution C and the mixed solution B are fully stirred and mixed to form a mixed material D, the mixed material D is fully aged;

[0067] S5: adding a friction agent to the mixture D and mixing thoroughly to obtain a mixture E;

[0068] S6: adding a foaming agent to the mixture E and mixing thoroughly to obtain a mixture F;

[0069] S7: adding essence to the mixed material F, homogenizing and degassing to obtain the product, and then filling it into toothpaste in a conventional manner.

[0070] Example 2

[0071] This example provides the use of patchouli ketone in the preparation of an anti-caries oral care agent.

[0072] This example also provides the use of the anti-caries oral care agent obtained by the above operation in the preparation of toothpaste, which is different from Example 1 in that the weight portion of the anti-caries oral care agent (i.e., patchouli ketone) is 0.02 parts.

[0073] Example 3

[0074] This example provides the use of patchouli ketone in the preparation of an anti-caries oral care agent.

[0075] This example also provides the use of the anti-caries oral care agent obtained by the above operation in the preparation of toothpaste, which is different from Example 1 in that the weight portion of the anti-caries oral care agent (i.e., patchouli ketone) is 0.04 parts.

[0076] Example 4

[0077] This example provides an anti-caries oral care agent, which is composed of the following components in percentage by weight: 0.02 parts of patchouli ketone and 0.003 parts of magnolol.

[0078] This example also provides the use of the above-mentioned anti-caries oral care agent in the preparation of toothpaste, which is different from Example 1 in that the weight portion of the anti-caries oral care agent is 0.023 parts.

[0079] Example 5

[0080] This example provides an anti-caries oral care agent, which is composed of the following components in percentage by weight: 0.02 parts of patchouli ketone and 0.1 parts of citral.

[0081] This example also provides the use of the above-mentioned anti-caries oral care agent in the preparation of toothpaste, which is different from Example 1 in that the weight portion of the anti-caries oral care agent is 0.12 parts.

[0082] Example 6

[0083] This example provides an anti-caries oral care agent, which is composed of the following components in percentage by weight: 0.01 parts of patchouli ketone and 1.2 parts of bornyl acetate.

[0084] This example also provides the use of the above-mentioned anti-caries oral care agent in the preparation of toothpaste, which is different from Example 1 in that the weight portion of the anti-caries oral care agent is 1.21 parts.

[0085] Example 7

[0086] This example provides an anti-caries oral care agent, which is composed of the following components in percentage by weight: 0.01 part of patchouli ketone, 0.01 part of magnolol, 0.05 part of citral, and 0.5 part of borneol acetate.

[0087] This example also provides the use of the above-mentioned anti-caries oral care agent in the preparation of toothpaste, which is different from Example 1 in that the weight portion of the anti-caries oral care agent is 0.57 parts.

[0088] Example 8

[0089] This example provides an anti-caries oral care agent, which is composed of the following components in weight percentage: 0.01 parts of patchouli ketone, 0.01 parts of magnolol, 0.05 parts of citral, 0.05 parts of ethyl p-methoxycinnamate, 0.5 parts of borneol acetate, and 0.2 parts of β-caryophyllene.

[0090] This example also provides the use of the above-mentioned anti-caries oral care agent in the preparation of toothpaste, which is different from Example 1 in that the weight portion of the anti-caries oral care agent is 0.82 parts.

[0091] Comparative Example 1

[0092] This example provides an anti-caries oral care agent, which is composed of the following components in percentage by weight: 0.02 parts of patchouli ketone and 0.3 parts of β-caryophyllene.

[0093] This example also provides the use of the above-mentioned anti-caries oral care agent in the preparation of toothpaste, which is different from Example 1 in that the weight portion of the anti-caries oral care agent is 0.32 parts.

[0094] The toothpaste formulas in the embodiments and comparative examples are specifically shown in Table 1 below:

[0095] Table 1 Antibacterial and anti-caries toothpaste formula (unit: mass percentage)

[0096]

[0097]

[0098] The total mass percentage of toothpaste is 100%. When the sum of the mass percentages of other toothpaste raw materials is less than 100%, the remainder is supplemented with water.

[0099] Test Case

[0100] This example tests the anti-caries effect of the toothpaste. The specific operation is to take the toothpaste prepared in the above embodiment and comparative example and test its antibacterial effect on Streptococcus mutans.

[0101] 1) Preparation of Streptococcus mutans suspension

[0102] The activated standard strain of Streptococcus mutans (ATCC 25175, commercially available) was picked and inoculated on the RCA plate and evenly spread, and then inverted and placed in an anaerobic bag. After culturing in a 37°C incubator for 24 hours, the bacterial moss was scraped from the plate with a disposable sterile inoculation loop, suspended in sterile PBS to prepare a bacterial solution, and streaked on the RCA plate for culturing. After anaerobic culture for 24 hours, a single colony was picked and anaerobically cultured in a BHI liquid culture medium at 37°C and 180 rpm in a shaking incubator; the bacteria in the logarithmic growth period were taken and the absorbance (OD) was adjusted to 1.0 at a wavelength of 600 nm using an ultraviolet spectrophotometer, and used as the standard bacterial solution for later use.

[0103] 2) Patchouli ketone growth curve test of Streptococcus mutans

[0104] The experimental group diluted pogostone to three geometric ratios (1 / 2 MIC, 1 / 4 MIC, 1 / 8 MIC) at and below the MIC. 1 mL was taken and added to a test tube, and then 1 mL of the working bacterial solution diluted 100 times with the standard bacterial solution was added. The bacterial solution control group (Control) was added with the DMSO solution and bacterial solution at the same concentration as the MIC group. Each group was set with 6 parallel groups. One tube was taken at 0, 4, 8, 12, 24, and 48 h to measure the OD 600 value and draw a growth curve graph.

[0105] The growth curve is as Figure 1 shown. It can be seen from the figure that compared with the control group, pogostone can significantly inhibit the growth of Streptococcus mutans. The control group entered the logarithmic growth phase at 4 h and reached the plateau phase at 12 h; while the MIC group and the 1 / 2 MIC group could significantly inhibit the growth of Streptococcus mutans.

[0106] 3) Joint drug sensitivity test of pogostone and other active ingredients

[0107] Using Streptococcus mutans as the indicator bacterium, the MICs of pogostone, honokiol, citral, ethyl p-methoxycinnamate, bornyl acetate, and β-caryophyllene were measured, and the 2, 1, 1 / 2, 1 / 4, 1 / 8, 1 / 16, and 1 / 32 times of the MICs of pogostone and each compound were designed by the checkerboard method with BHI medium for a 7×7 joint test. The bacterial solution concentration was set the same as in the part of the pogostone growth curve determination test for Streptococcus mutans, the optimal combined effect concentration was selected, and the fractional inhibitory concentration index (FICI) was calculated.

[0108] The calculation formula of FICI is as follows:

[0109]

[0110] Judgment criteria: FICI ≤ 0.5, synergistic effect; 0.5 < FICI ≤ 1, additive effect; 1 < FICI ≤ 2, no effect; FICI > 2, antagonistic effect.

[0111] The test results showed that the MIC value of pogostone was 100 μg / ml, the MIC value of honokiol was 12.5 μg / ml, the MIC value of citral was 400 μg / ml, the MIC value of ethyl p-methoxycinnamate was 400 μg / ml, the MIC value of bornyl acetate was 6.4 mg / ml, and the MIC value of β-caryophyllene was 1.6 mg / ml.

[0112] The joint drug sensitivity test showed that:

[0113] For patchouli ketone and magnolol, the best combined effect concentration was 1 / 8 MIC concentration of magnolol and 1 / 4 MIC concentration of patchouli ketone, and the FICI value was 0.375, indicating that the combined use of patchouli ketone and magnolol had a synergistic effect on the inhibition of Streptococcus mutans.

[0114] For patchouli ketone and citral, the best combined effect concentration was 1 / 4MIC concentration of patchouli ketone and 1 / 4MIC concentration of citral, and the FICI value was 0.5, indicating that the combined use of patchouli ketone and citral had a synergistic effect on the inhibition of Streptococcus mutans.

[0115] For patchouli ketone and bornyl acetate, the best combination effect concentration was 1 / 16MIC concentration of patchouli ketone and 1 / 4MIC concentration of bornyl acetate, and the FICI value was 0.3125, indicating that the combined use of patchouli ketone and bornyl acetate had a synergistic effect on the inhibition of Streptococcus mutans.

[0116] For patchouli ketone and ethyl p-methoxycinnamate, the optimal combined effect concentration was 1 / 2MIC concentration of patchouli ketone and 1 / 2MIC concentration of ethyl p-methoxycinnamate, and the FICI value was 1, indicating that the combined use of patchouli ketone and ethyl p-methoxycinnamate had an additive effect on the antibacterial effect of Streptococcus mutans.

[0117] For patchouli ketone and β-caryophyllene, the best combined effect concentration was 1 / 2MIC concentration of patchouli ketone and 1 / 4MIC concentration of β-caryophyllene, and the FICI value was 0.75, indicating that the combined use of patchouli ketone and β-caryophyllene had an additive effect on the antibacterial effect of Streptococcus mutans.

[0118] 4) Evaluation test of the antibacterial effect of compound antibacterial and anti-caries toothpaste containing patchouli ketone

[0119] The antibacterial effect of the toothpaste in the examples and comparative examples was investigated by referring to "5.1.2 Carrier Immersion Quantitative Antibacterial Test" in the "Health Industry Standards of the People's Republic of China". Mutans Streptococcus was diluted with PBS to about 5×10 6 CFU / mL~5×10 7CFU / mL is used to make a bacterial suspension for later use. Take 10μL of the bacterial suspension on a drug-sensitive paper, dry it at 36℃±1℃ or air it at room temperature for later use. Weigh 5g / piece of the toothpaste sample prepared in the embodiment or comparative example into a sterile plate, place it in a 20℃±1℃ water bath for 5min, take the above-mentioned drug-sensitive paper with sterile tweezers, and immerse the carrier completely in the sample, and time it for 5min. Then take out the drug-sensitive paper and add it to a 5.0mL PBS test tube, mix it, oscillate it, wash off the test bacteria, absorb 1.0mL of the sample solution, and determine the number of surviving bacteria according to the live bacteria culture counting method. Inoculate 2 plates with each tube of sample solution. If the number of colonies growing on the plate is large, PBS can be used for 10-fold serial dilution, and then live bacteria culture counting can be performed. Take 10.0g of blank toothpaste matrix that does not contain antibacterial and anti-caries active ingredients and soak it in 2 drug-sensitive paper sheets for parallel experiments as a positive control. The amount of bacteria recovered in the positive control is 1.0×10 4 CFU / piece~9.0×10 4 CFU / piece. Take PBS and culture medium from the same batch as negative control. All test samples and control samples were cultured at 36℃±1℃, and the results were observed for 24 hours. The test was repeated 3 times and the inhibition rate was calculated.

[0120] The antibacterial rate calculation method is as follows:

[0121]

[0122] Where:

[0123] X—inhibition rate, %;

[0124] A0—average colony count of control samples, in CFU / piece;

[0125] A1—Average colony count of the tested samples, in CFU / piece.

[0126] The test results are shown in Table 2.

[0127] Table 2 Test results of antibacterial rate of toothpaste against Streptococcus mutans in Examples and Comparative Examples

[0128] Toothpaste No. Antibacterial rate (%) Example 1 50.2±0.3 Example 2 68.3±0.1 Example 3 94.9±0.3 Example 4 90.4±0.2 Example 5 87.5±0.5 Example 6 82.5±0.4 Example 7 99.8±0.1 Example 8 99.9±0.1 Comparative Example 1 75.7±0.7

[0129] If the inhibition rate is ≥50% to 90%, it is judged to have an antibacterial effect; if the inhibition rate is ≥90%, it is judged to have a strong antibacterial effect.

[0130] The test results show that all embodiments of the present invention have antibacterial effects, and the antibacterial effect of the compound solution is significantly improved, especially when it contains multiple ingredients, which can be increased to more than 99.8%.

[0131] 5) Toothpaste quality evaluation

[0132] The quality of the antibacterial and anti-caries toothpaste containing Patchouli alcohol prepared by the method of the embodiment was tested. With reference to the sensory and physical and chemical indicators in GB / T8372-2017 Toothpaste, the quality evaluation was carried out using the paste form, stability and foam volume as a comprehensive evaluation method.

[0133] Evaluation of forming condition and paste morphology: Take a toothpaste sample, squeeze 2cm from a 8mm diameter mouth onto a toothbrush. The toothpaste prepared in this embodiment is easy to squeeze out, has obvious wire drawing, is easy to cut, and has no obvious collapsed area; the paste is clean and delicate, with uniform color, bright and free of impurities.

[0134] Stability evaluation: Take 2 toothpaste samples, store one sample at room temperature; put the other sample into a refrigerator at (-8±1)℃ for 8 hours, then take it out, and then put it into a constant temperature incubator at (45±1)℃ for 8 hours, then take it out, restore it to room temperature, open the cover, the paste should not overflow from the tube, turn the toothpaste tube upside down, and no liquid should drip from the tube within 10 seconds; compare the paste with the room temperature sample after squeezing it out. The toothpaste prepared in this embodiment does not overflow from the tube, does not separate liquid, and the fragrance body has normal color.

[0135] Foam volume evaluation: pre-weigh 45°C, 20mL water, weigh 1g of the toothpaste to be tested in a beaker, add a small amount of water to dissolve the paste, pour the dissolved paste into a stoppered measuring cylinder, wash the beaker with the remaining water, pour it into the measuring cylinder, cover and tighten the stopper, shake the solution in the measuring cylinder with the maximum force, stop after the paste is completely dissolved, place the measuring cylinder on the operating table and let it stand for 5min, record the foaming amount based on the most concentrated position of the foam distribution in the measuring cylinder, repeat 3 times, and take the average value. The foam volume of the toothpaste prepared in each embodiment of the present invention is ≥90mL, which meets the corresponding national standards.

[0136] The mechanism of action of each component in the anti-caries oral care agent of the present invention is speculated as follows:

[0137] Patchouli ketone, as an active ingredient carefully extracted from patchouli volatile oil, is not only the core material basis for the efficacy of patchouli, but also exhibits excellent physical solubility - it is miscible with water and compatible with a variety of organic solvents (such as alcohols, ethers and esters). This feature greatly broadens its application range and simplifies the use process. The pharmacological effects of patchouli ketone are extensive and profound, covering anti-inflammatory, antibacterial, antioxidant, antiviral, anti-tumor, gastric protection, brain protection, immunomodulation and insecticide. These characteristics together give it huge market potential and application value in the pharmaceutical, food and health care products industries. Through in-depth research, this program revealed that patchouli ketone has a good inhibitory effect on Streptococcus mutans. This discovery has opened up a new path for the application of patchouli ketone in oral care products, indicating that by incorporating it into oral care products, it can be expected to obtain ideal antibacterial and anti-caries effects, thereby providing users with more efficient and safe oral health protection.

[0138] The Chinese herbal medicine Magnolia officinalis has been widely reported in scientific literature and has significant therapeutic potential for a variety of infectious diseases, including periodontitis. Magnolia officinalis, as the main active ingredient in Magnolia officinalis, is classified as a biphenol compound and exhibits a wide range of inhibitory effects on a variety of bacteria. In recent years, research on magnolia officinalis in the field of oral health has focused on its inhibitory effects on cariogenic bacteria such as Streptococcus mutans, aiming to delay the progression of caries by controlling the growth of such bacteria. The antibacterial and anti-inflammatory mechanisms of magnolia officinalis are complex and profound, and may involve regulating key signaling pathways such as tumor necrosis factor TNF-α, phosphatidylinositol 3-kinase / protein kinase B (PI3K / Akt), and mitogen-activated protein kinase (MAPK), thereby exerting anti-inflammatory effects. In addition, magnolia officinalis can also regulate the expression balance of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL), which helps to reduce alveolar bone resorption and promote bone regeneration, and has a positive effect on alleviating clinical symptoms associated with periodontitis. Given the excellent performance of magnolol in fighting Streptococcus mutans, it has good application prospects in oral care products.

[0139] Citral, whose chemical name is 3,7-dimethyl-2,6-octadienal-1, is a colorless to slightly yellow liquid with a strong lemon aroma. This compound exists in nature mainly as a mixture of two monoterpenoid isomers and is widely distributed in plants such as lemongrass, verbena, and Litsea cubeba. Citral has attracted much attention for its diverse biological activities, including antiseptic and antibacterial, insecticidal, anti-inflammatory, anticancer and antioxidant. In the food industry, citral has received particular attention for its significant antibacterial and antifungal activities. Its strong antibacterial ability not only helps to extend the shelf life of food, but also improves the safety and quality of food. Therefore, citral has broad application prospects in food preservation, antiseptic and enhancing food flavor.

[0140] Bornyl acetate, as the core component in the volatile oil of Amomum villosum, is not only widely used in cosmetics, soaps, indoor air fresheners, indoor spray fragrances, bath fragrances and talcum powders due to its unique aromatic properties, but also has attracted extensive attention from the scientific community due to its potential biological activity. The present invention unexpectedly found that bornyl acetate can effectively inhibit the growth of multiple harmful bacteria in the oral cavity, including those bacteria closely related to the formation of dental caries. By reducing the number of these bacteria, bornyl acetate helps to reduce the formation of dental plaque, thereby slowing down the development of dental caries. In addition, its anti-inflammatory effect also helps to reduce oral inflammation and promote the health of oral tissues. Therefore, when it is applied to oral care with porphyrin, it can be synergistically antibacterial and anti-inflammatory, and significantly prevent dental caries. Therefore, based on these biological characteristics of bornyl acetate, it has a scientific basis to be applied to anti-caries products, and is expected to provide a new and effective means for preventing dental caries.

[0141] The β-caryophyllene used in this technical solution is derived from the essential oil of the condiment Murraya oleifera, which is carefully extracted by steam distillation and successfully precipitated through a subsequent crystallization process. According to the research results of this solution, β-caryophyllene exhibits a certain inhibitory effect on Streptococcus mutans. This discovery not only reveals the potential application value of β-caryophyllene in the field of oral health, but also provides a scientific basis for the development of new anti-caries products.

[0142] Ethyl p-methoxycinnamate is a key component of Kaempferia galanga. Existing scientific research has confirmed that this compound has significant antibacterial activity against a variety of microorganisms such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger. On this basis, this technical solution further explored and found that ethyl p-methoxycinnamate also showed a good inhibitory effect on Streptococcus mutans. This new discovery not only enriches the antibacterial spectrum of ethyl p-methoxycinnamate, but also opens up broad prospects for its application in oral care products, indicating that this ingredient has certain potential in preventing caries and maintaining oral health.

[0143] The embodiments of the present invention are described in detail above, but the present invention is not limited to the above embodiments. Various changes can be made within the knowledge scope of ordinary technicians in the relevant technical field without departing from the purpose of the present invention.

Claims

1. Application of patchouli ketone in the preparation of anti-caries oral care agents.

2. An anti-caries oral care agent, characterized in that: The invention comprises an anti-caries component I and an anti-caries component II, wherein the anti-caries component I is patchouli ketone, and the anti-caries component II comprises at least one of magnolol, citral or bornyl acetate.

3. The anti-caries oral care agent according to claim 2, characterized in that: The anti-caries oral care agent also includes at least one of β-caryophyllene or ethyl p-methoxycinnamate.

4. The anti-caries oral care agent according to claim 3, characterized in that: The anti-caries oral care agent further comprises beta-caryophyllene and ethyl p-methoxycinnamate; and the anti-caries component II comprises magnolol, citral and bornyl acetate.

5. The anti-caries oral care agent according to claim 3, characterized in that: The weight proportion of patchouli ketone in the anti-caries oral care agent is 6% to 99.9%.

6. An oral care product, characterized in that: The method comprises a base material and the anti-caries oral care agent according to any one of claims 2 to 5.

7. The oral care product according to claim 6, characterized in that: The oral care product includes at least one of toothpaste, tooth powder, liquid toothpaste, mouthwash, tooth paste, chewing gum, oral spray or tooth gel.

8. The oral care product according to claim 7, characterized in that: The toothpaste comprises the following raw materials in parts by weight: 0.0025-0.04 parts of patchouli ketone, 0.000310-0.006 parts of magnolol, 0.0025-0.16 parts of citral, 0.0025-0.16 parts of ethyl p-methoxycinnamate, 0.04-2.56 parts of bornyl acetate, 0.01-0.64 parts of beta-caryophyllene and 70-90 parts of base material.

9. A method for preparing an oral care toothpaste, characterized in that: The steps include: S1, dispersing the thickener in the humectant to form a mixed solution A after swelling; S2, adding part of water to the anti-caries oral care agent according to any one of claims 2 to 5 to form a mixed solution B; S3, adding a sweetener, a preservative and the remaining water to the mixed solution A to obtain a mixed solution C; S4, mixing the mixed solution C with the mixed solution B to form a mixed material D, and then aging it; S5, adding a friction agent to the mixture D and mixing to obtain a mixture E; S6, adding a foaming agent to the mixed material E and mixing the mixture to obtain a mixed material F; S7. Add essence to the mixture F to obtain the oral care toothpaste.

10. The method for preparing the oral care toothpaste according to claim 9, characterized in that: The mass fraction of the anti-caries oral care agent in the mixed solution B is 5% to 15%.

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