Anti-fatigue composition and preparation method and use thereof

Abstract

The present invention belongs to the technical field of anti-fatigue drug research, and specifically relates to an anti-fatigue composition and its preparation method and use. The composition is composed of the following raw materials by weight: 4-6 parts of orange peel essential oil, 4-6 parts of peppermint essential oil, 2-3 parts of lemon essential oil, 1-2 parts of eucalyptus essential oil, 1-3 parts of gardenia essential oil, 1-2 parts of ginkgo essential oil, and 0.03 parts of osmanthus extract; the osmanthus extract is a concentrate of osmanthus after water extraction.

Description

Technical Field

[0001] The invention belongs to the technical field of anti-fatigue drug research, and specifically relates to an anti-fatigue composition and a preparation method and use thereof. Background Art

[0002] In recent years, with the continuous breakthroughs in the field of aromatic drugs, the number of anti-fatigue drugs has been greatly enriched and their application scope has been expanded, which has also brought great help to the clinical prevention and treatment of related diseases. After inhalation of aromatic drugs, due to the unique physiological and anatomical connection between the nasal mucosa and the brain, the drugs can be directly delivered to the brain through the olfactory area at the top of the nasal cavity. Based on this, simple, efficient and safe drugs for refreshing the mind can be developed, and suitable volatile oil products for nasal delivery to the brain can also be designed in combination with traditional Chinese medicine theory.

[0003] Chinese medicine volatile oil and aromatic drugs are a class of Chinese medicines that are immiscible with water, volatile and have special smells. The ingredients are very complex, and the sources are different, and the effects are different. They have effects in the cardiovascular system, central nervous system, respiratory system, gastrointestinal system, antibacterial, anti-inflammatory, anti-tumor, antiviral and promoting drug absorption. In recent years, the research on Chinese medicine volatile oil and aromatic drugs has increased day by day, and has shown broad application prospects in medicine. Therefore, the present invention intends to develop an anti-fatigue product with good effect with Chinese medicine volatile oil as the main component. Summary of the invention

[0004] In view of the above technical problems, the present invention provides an anti-fatigue composition

[0005] The specific technical solutions provided by the present invention are as follows:

[0006] The first aspect of the present invention provides an anti-fatigue composition, which is composed of the following raw materials by weight: 4-6 parts of orange peel essential oil, 4-6 parts of peppermint essential oil, 2-3 parts of lemon essential oil, 1-2 parts of eucalyptus essential oil, 1-3 parts of gardenia essential oil, 1-2 parts of ginkgo essential oil, and 0.03 parts of osmanthus extract; the osmanthus extract is a concentrate of osmanthus after water extraction.

[0007] Preferably, the composition is composed of the following raw materials by weight: 5 parts of orange peel essential oil, 5 parts of peppermint essential oil, 2 parts of lemon essential oil, 2 parts of eucalyptus essential oil, 2 parts of gardenia essential oil, 1 part of ginkgo essential oil, and 0.03 parts of osmanthus extract; the osmanthus extract is a concentrate of osmanthus after water extraction.

[0008] The second aspect of the present invention provides a method for preparing the anti-fatigue composition, which is carried out according to the following steps:

[0009] The orange peel essential oil, peppermint essential oil, lemon essential oil, eucalyptus essential oil, gardenia essential oil, ginkgo essential oil and osmanthus extract are weighed in parts by weight, mixed, heated, mixed evenly, refrigerated and fermented to obtain the product.

[0010] Preferably, the refrigerated fermentation is a natural fermentation at 2-8°C for 2-3 days.

[0011] The third aspect of the present invention provides a use of the anti-fatigue composition in preparing an anti-fatigue product.

[0012] Preferably, the product is an external preparation.

[0013] Preferably, the external preparation is an ointment, a patch, a film coating, a spray, an aerosol, a wet compress, an ointment or a gel. When preparing the external preparation, suitable excipients such as a wetting agent, an antioxidant, a pH regulator, a thickener, an emulsifier, a preservative, etc. are added according to the selected dosage form.

[0014] Preferably, the patch is prepared according to the following steps:

[0015] The anti-fatigue composition and the hydrogel matrix are mixed and coated on a backing material, covered with a pressure-sensitive adhesive material, and then pressed on an anti-adhesive layer, and the backing material is preferably artificial skin.

[0016] Preferably, the usage ratio of the anti-fatigue composition to the hydrogel matrix is ​​0.01 mL: 1.8 g; and the pressure-sensitive adhesive material is silicone pressure-sensitive adhesive.

[0017] Preferably, the hydrogel matrix is ​​prepared according to the following steps:

[0018] Weigh methylcellulose and α-cyclodextrin in a mass ratio of 5:2;

[0019] Prepare a sodium chloride solution with a mass concentration of 30%;

[0020] Add the methyl cellulose to the sodium chloride solution at a ratio of 50 mL: 1 g, heat and swell, then add the α-cyclodextrin, mix well, and dry to obtain the hydrogel matrix; or

[0021] Weigh methylcellulose, α-cyclodextrin and pectin in a mass ratio of 0.8-1.2:0.4:0.2;

[0022] The methyl cellulose is added to water in a ratio of 20-30 mL: 0.8-1.2 g, heated to swell, and then the α-cyclodextrin and pectin are added, heated to produce flocs, and the flocs are dried to obtain the hydrogel matrix.

[0023] Compared with the prior art, the beneficial effects of the present invention are:

[0024] The patch prepared by the anti-fatigue composition provided by the present invention is an invisible aromatic Chinese medicine anti-fatigue sober patch, which adopts invisible anti-biotic artificial skin, adds essential oil prepared by aromatic plant extracts, and is pressed into a sheet patch. The product is designed in combination with the certain volatility of aromatic compounds, which can effectively relieve fatigue and achieve a refreshing effect in a short time; the compact appearance design also conforms to the aesthetics of contemporary people.

[0025] The anti-fatigue patch prepared using the composition provided by the present invention has the following advantages:

[0026] ① Portability: This product is in the shape of a circular sheet with a radius of about 1 cm, which is small and easy to carry.

[0027] ②Safety: It uses high-quality natural herbal ingredients and has a certain degree of safety in terms of raw materials.

[0028] ③Invisibility: It uses a hydrocolloid patch made of artificial skin made of medical polymer material. Its material and color are similar to human skin, and it can show the original skin color to the greatest extent after fitting.

[0029] ④ Aromaticity: It utilizes the unique aroma of aromatic Chinese medicine, which is different from the pungent smell of similar products on the market and is an excellent olfactory enjoyment.

[0030] ⑤Developability: It can be transformed into corresponding states of different sizes and appearances according to various requirements of the applicable population and various scenarios. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is a schematic diagram of the structure of the anti-fatigue patch; 1. backing layer (artificial skin); 2+3. essential oil hydrogel matrix; 4. adhesive layer; 5. anti-adhesive layer;

[0032] Figure 2 This is a physical picture of the anti-fatigue patch;

[0033] Figure 3 This is a diagram of the use status of the anti-fatigue patch;

[0034] Figure 4 is the average weighted swimming time of each group. DETAILED DESCRIPTION

[0035] The following embodiments are only used to more clearly illustrate the technical solutions of the present invention and are therefore only used as examples and are not intended to limit the scope of protection of the present invention.

[0036] The orange peel essential oil, peppermint essential oil, lemon essential oil, eucalyptus essential oil, gardenia essential oil, ginkgo essential oil, and osmanthus extract used in the present invention are all commercially available, and those skilled in the art can also extract them according to the conventional essential oil extraction method. Osmanthus extract is a concentrate of osmanthus after water extraction, specifically, it is obtained by using water as the extraction solvent and adopting the heating reflux method.

[0037] The sources of raw materials are shown in Table 1.

[0038] Table 1 Source of raw materials

[0039]

[0040] Example 1

[0041] An anti-fatigue composition is prepared by the following method:

[0042] Take 6ml of orange peel essential oil, 4ml of peppermint essential oil, 3ml of lemon essential oil, 2ml of eucalyptus essential oil, 2ml of gardenia essential oil, and 1ml of ginkgo essential oil. Add the above essential oils to the measuring cup in turn, mix well, accurately weigh 0.03g of osmanthus extract and add it to the cup, cover the cup mouth with plastic wrap, place it in a 75 degrees Celsius water bath and heat it until the osmanthus extract is dissolved in the essential oil. Place the prepared essential oil in a 2 degrees Celsius refrigerated fermentation for 3 days, take it out after the refrigeration is over, and add 30ml of 50% medical alcohol.

[0043] Example 2

[0044] An anti-fatigue composition is prepared by the following method:

[0045] Take 6ml of orange peel essential oil, 4ml of peppermint essential oil, 3ml of lemon essential oil, 2ml of eucalyptus essential oil, 2ml of gardenia essential oil, and 1ml of ginkgo essential oil. Add the above essential oils to the measuring cup in turn, mix well, accurately weigh 0.03g of osmanthus extract and add it to the cup, cover the cup mouth with plastic wrap, place it in a 75 degrees Celsius water bath and heat it until the osmanthus extract is dissolved in the essential oil. Place the prepared essential oil in a refrigerated fermentation at 8 degrees Celsius for 2 days, take it out after the refrigeration is over, and add 30ml of 50% medical alcohol.

[0046] Example 3

[0047] An anti-fatigue composition is prepared by the following method:

[0048] Take 6ml of orange peel essential oil, 4ml of peppermint essential oil, 3ml of lemon essential oil, 2ml of eucalyptus essential oil, 2ml of gardenia essential oil, and 1ml of ginkgo essential oil. Add the above essential oils to the measuring cup in turn, mix well, accurately weigh 0.03g of osmanthus extract and add it to the cup, cover the cup mouth with plastic wrap, place it in a 75 degrees Celsius water bath and heat it until the osmanthus extract is dissolved in the essential oil. Place the prepared essential oil in a 2 degrees Celsius refrigerated fermentation for 3 days, take it out after the refrigeration is over, and add 30ml of 40% medical alcohol.

[0049] Example 5

[0050] An anti-fatigue composition is prepared by the following method:

[0051] Take 7.5ml of orange peel essential oil, 5ml of peppermint essential oil, 4ml of lemon essential oil, 2ml of eucalyptus essential oil, 3ml of gardenia essential oil, and 2ml of ginkgo essential oil. Add the above essential oils to the measuring cup in turn, mix well, accurately weigh 0.03g of osmanthus extract and add it to the cup, cover the cup mouth with plastic wrap, place it in a 75 degrees Celsius water bath and heat it until the osmanthus extract is dissolved in the essential oil. Place the prepared essential oil in a refrigerated fermentation at 8 degrees Celsius for 2 days, take it out after the refrigeration is over, and add 30ml of 50% medical alcohol.

[0052] Example 6

[0053] An anti-fatigue composition is prepared by the following method:

[0054] Take 5ml of orange peel essential oil, 3ml of peppermint essential oil, 2.5ml of lemon essential oil, 1ml of eucalyptus essential oil, 1ml of gardenia essential oil, and 1ml of ginkgo essential oil. Add the above essential oils to the measuring cup in turn, mix well, accurately weigh 0.03g of osmanthus extract and add it to the cup, cover the cup mouth with plastic wrap, place it in a 75 degrees Celsius water bath and heat it until the osmanthus extract is dissolved in the essential oil. Place the prepared essential oil in a refrigerated fermentation at 8 degrees Celsius for 2 days, take it out after the refrigeration is over, and add 30ml of 50% medical alcohol.

[0055] Example 7

[0056] An anti-fatigue patch is prepared by the following method:

[0057] Prepare a sodium chloride solution with a mass concentration of 30%, take 250 mL of the sodium chloride solution, add 5 g of methyl cellulose, heat and swell, then add 2 g of α-cyclodextrin, mix well, and dry to obtain a hydrogel matrix;

[0058] Take 1.8g matrix and mix two drops (about 0.01ml) of essential oil prepared by Example 1. If you need to expand production, you can amplify it in equal proportion. The essential oil matrix after mixing is evenly coated on the artificial skin, covered with silicone pressure-sensitive adhesive material, pressed on the anti-adhesive layer prepared in advance, and then carried out secondary tableting to make it more firm, and then cut it according to the required specifications for production.

[0059] The actual picture of the prepared patch is as follows Figure 2 As shown, the state diagram is as follows Figure 3 shown.

[0060] Example 8

[0061] An anti-fatigue patch is prepared by the following method:

[0062] (1) Matrix preparation

[0063] Weigh 2.0 g of methyl cellulose (MC), 0.8 g of α-cyclodextrin (α-CD), and 0.4 g of pectin on an analytical balance for later use; take 60 ml of distilled water, add it into a 250 ml beaker, place it on a magnetic stirrer, slowly add 2.0 g of MC under stirring, slowly stir and heat to 70°C and keep constant temperature for 15 min; add 50 ml of distilled water and stir for 5 min until swelling is complete; cool to room temperature to obtain a viscous fluid; stir and add 0.8 g of cyclodextrin and 0.5 g of pectin, heat to 70°C under magnetic stirring, white flocculent material appears on the upper layer, stop heating, remove water, and dry the flocculent to obtain a hydrogel matrix.

[0064] (2) Take 2.0g of the matrix and mix two drops (about 0.05ml) of the essential oil prepared in Example 1. If you need to expand production, you can enlarge it in equal proportion. The essential oil matrix after mixing is evenly coated on the artificial skin, covered with a silicone pressure-sensitive adhesive material, pressed on the anti-adhesive layer prepared in advance, and then carried out secondary tableting to make it more firm, and then cut it according to the required specifications for production.

[0065] The schematic diagram of the prepared patch structure is shown in Figure 1 shown.

[0066] Example 9

[0067] An anti-fatigue patch is prepared by the following method:

[0068] (1) Matrix preparation

[0069] Weigh 1.8 g of methyl cellulose (MC), 1.0 g of α-cyclodextrin (α-CD), and 0.5 g of pectin on an analytical balance for later use; take 60 ml of distilled water, add it into a 250 ml beaker, place it on a magnetic stirrer, slowly add 2.2 g of MC under stirring, slowly stir and heat to 70°C and keep constant temperature for 15 min; add 60 ml of distilled water and stir for 5 min until swelling is complete; cool to room temperature to obtain a viscous fluid; stir and add 1.0 g of cyclodextrin and 0.5 g of pectin, heat to 70°C under magnetic stirring, white flocculent material appears on the upper layer, stop heating, remove water, and dry the flocculent to obtain a hydrogel matrix.

[0070] (2) Take 1.6g of the matrix and mix two drops (about 0.05ml) of the essential oil prepared in Example 1. If you need to expand production, you can enlarge it in equal proportion. The essential oil matrix after mixing is evenly coated on the artificial skin, covered with a silicone pressure-sensitive adhesive material, pressed on the anti-adhesive layer prepared in advance, and then carried out secondary tableting to make it more firm, and then cut it according to the required specifications for production.

[0071] Example 10

[0072] An anti-fatigue patch is prepared by the following method:

[0073] (1) Matrix preparation

[0074] Weigh 1.8 g of methyl cellulose (MC), 0.6 g of α-cyclodextrin (α-CD), and 0.3 g of pectin on an analytical balance for later use; take 50 ml of distilled water, add it into a 250 ml beaker, place it on a magnetic stirrer, slowly add 1.8 g of MC under stirring, slowly stir and heat to 70°C and keep constant temperature for 15 min; add 500 ml of distilled water and stir for 5 min until swelling is complete; cool to room temperature to obtain a viscous fluid; stir and add 0.6 g of cyclodextrin and 0.3 g of pectin, heat to 70°C under magnetic stirring, white flocculent material appears on the upper layer, stop heating, remove water, and dry the flocculent to obtain a hydrogel matrix.

[0075] (2) Take 2.0g of the matrix and mix two drops (about 0.05ml) of the essential oil prepared in Example 1. If you need to expand production, you can enlarge it in equal proportion. The essential oil matrix after mixing is evenly coated on the artificial skin, covered with a silicone pressure-sensitive adhesive material, pressed on the anti-adhesive layer prepared in advance, and then carried out secondary tableting to make it more firm, and then cut it according to the required specifications for production.

[0076] Embodiment 11

[0077] An anti-fatigue patch is prepared by the following method:

[0078] (1) Matrix preparation

[0079] Weigh 2.2 g of methyl cellulose (MC), 1.0 g of α-cyclodextrin (α-CD), and 0.3-0.5 g of pectin on an analytical balance for later use; take 60 ml of distilled water, add it into a 250 ml beaker, place it on a magnetic stirrer, slowly add 2.2 g of MC under stirring, slowly stir and heat to 70°C and keep constant temperature for 15 min; add 60 ml of distilled water and stir for 5 min until swelling is complete; cool to room temperature to obtain a viscous fluid; stir and add 1.0 g of cyclodextrin and 0.5 g of pectin, heat to 70°C under magnetic stirring, white flocculent material appears on the upper layer, stop heating, remove moisture, and dry the flocculent to obtain a hydrogel matrix.

[0080] (3) Take 2.0g of the matrix and mix two drops (about 0.05ml) of the essential oil prepared in Example 1. If you need to expand production, you can enlarge it in equal proportion. The essential oil matrix after mixing is evenly coated on the artificial skin, covered with a silicone pressure-sensitive adhesive material, pressed on the anti-adhesive layer prepared in advance, and then carried out secondary tableting to make it more firm, and then cut it according to the required specifications for production.

[0081] Example 12

[0082] An anti-fatigue patch is prepared by the following method:

[0083] Prepare a sodium chloride solution with a mass concentration of 30%, take 250 mL of the sodium chloride solution, add 5 g of methyl cellulose, heat and swell, then add 2 g of α-cyclodextrin, mix well, and dry to obtain a hydrogel matrix;

[0084] Take 1.6g matrix and mix two drops (about 0.01ml) of essential oil prepared by Example 1. If you need to expand production, you can amplify it in equal proportion. The essential oil matrix after mixing is evenly coated on the artificial skin, covered with silicone pressure-sensitive adhesive material, pressed on the anti-adhesive layer prepared in advance, and then carry out secondary tableting to make it more firm, and then cut it according to the required specifications for production.

[0085] Example 13

[0086] An anti-fatigue patch is prepared by the following method:

[0087] Prepare a sodium chloride solution with a mass concentration of 30%, take 250 mL of the sodium chloride solution, add 5 g of methyl cellulose, heat and swell, then add 2 g of α-cyclodextrin, mix well, and dry to obtain a hydrogel matrix;

[0088] Get 1.8g matrix and match one drop of essential oil (about 0.005ml) prepared by Example 1 and mix, if need to expand production, can be amplified in equal proportion. The essential oil matrix after mixing is evenly coated on artificial skin, covered with silicone pressure-sensitive adhesive material, pressed on the anti-adhesive layer prepared in advance, and then carry out secondary tableting to make it more firm, and then cut according to the required specification for production.

[0089] Since the anti-fatigue effects of the compositions or patches prepared in Examples 1 to 13 are substantially the same, the anti-fatigue patch prepared in Example 11 is used as an example to illustrate the effect.

[0090] Testing of patch performance

[0091] The results are shown in Table 2.

[0092] Table 2 Performance test data

[0093]

[0094] 1. Anti-fatigue effect verification data.

[0095] SPF ICR mice, 8 weeks old, weighing 18-22 g, were selected from experimental animals provided by Hangzhou Medical College. The mice in the weighted swimming experiment were attached with a wire weighing 5% of their body weight and placed in a homemade swimming bucket (d=20 cm, h=30 cm) with a water depth of (25±1) cm and a water temperature of (25±1)°C. The time from the beginning of the mouse's swimming to the time when the mouse completely sank under the water for 10 seconds without surfacing was recorded, which was the weighted exhaustion time of the mouse.

[0096] Thirty mice were divided into a blank group, an inhalation group (95% essential oil), and an injection group (0.1 ml (5% essential oil) 0.9% NaCl). The blank group did not receive any treatment and was directly subjected to a weighted swimming experiment; the inhalation group was placed in a closed environment (30 cm × 25 cm × 20 cm), and provided with 2 ml of 95% pre-prepared essential oil for 10 min, and then subjected to a weighted swimming experiment in a normal environment for 3 min of buffering; the injection group mice were intraperitoneally injected with 0.1 ml (5% essential oil) 0.9% NaCl, and a weighted swimming experiment was performed on the mice ten minutes after the injection.

[0097] The blank group (M = 107.28, SD = 38.48), the inhalation group (M = 227.28, SD = 60.08), and the injection group (M = 406.27, SD = 85.67) were subjected to a weighted swimming test, and the experimental data were analyzed using SPSS analysis software. The results are shown in Tables 3 to 8 and Figure 4 .

[0098] Table 3 Data of mouse anti-fatigue swimming experiment

[0099] Group Total time / s Average time / s Blank group 858.27 107.28375 Inhalation group 1818.29 227.28625 Injection group 3250.13 406.26625

[0100] Table 4 Results of robust test for equality of mean values

[0101]

[0102] Table 5 Normality test results

[0103]

[0104] Table 6 ANOVA results

[0105]

[0106] Table 7 Data description results

[0107]

[0108] Table 8 Multiple comparison results

[0109]

[0110] The results showed that compared with the blank group, the data of the inhalation group and the injection group showed that there were significant differences in the weighted swimming time of mice in different groups, F(2,13)=42.35, MSE=4143.153, p<0.5, r=0.90. Subsequent multiple comparisons showed that the weighted swimming time of mice in the injection group was significantly higher than that of the inhalation group (t(21)=5.56, P<0.05, d=2.78) and the blank group (t(21)=9.29, P<0.05, d=4.64), and the weighted swimming time of mice in the inhalation group was significantly higher than that of the blank group (t(21)=3.73, P<0.05, d=1.86).

[0111] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. These modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be included in the scope of the claims and specification of the present invention.

Claims

1. An anti-fatigue composition, characterized in that: The invention is composed of the following raw materials by weight: 4-6 parts of orange peel essential oil, 4-6 parts of peppermint essential oil, 2-3 parts of lemon essential oil, 1-2 parts of eucalyptus essential oil, 1-3 parts of gardenia essential oil, 1-2 parts of ginkgo essential oil, and 0.03 parts of osmanthus extract; the osmanthus extract is a concentrate of osmanthus extracted by water; The anti-fatigue composition is prepared by the following steps: weighing orange peel essential oil, peppermint essential oil, lemon essential oil, eucalyptus essential oil, gardenia essential oil, ginkgo essential oil, and osmanthus extract according to the above weight proportions, mixing, heating, and refrigerating for fermentation to obtain the composition; The refrigerated fermentation is a natural fermentation at 2-8°C for 2-3 days.

2. Use of the anti-fatigue composition according to claim 1 in the preparation of an anti-fatigue external preparation product, wherein the external preparation is a patch.

3. The use according to claim 2, characterized in that: The patch is prepared according to the following steps: Weigh methylcellulose, α-cyclodextrin and pectin in a mass ratio of 0.8-1.2:0.4:0.2; Add the methyl cellulose to water in a ratio of 20-30 mL: 0.8-1.2 g, heat and swell, then add the α-cyclodextrin and pectin, heat to form flocs, and dry the flocs to obtain a hydrogel matrix; The anti-fatigue composition of claim 1 and the hydrogel matrix are mixed in a dosage ratio of 0.008-0.012 mL: 1.6-1.8 g, coated on a backing material, covered with a silicone pressure-sensitive adhesive, and then pressed on an anti-adhesive layer, and obtained by secondary tableting.

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