Compound essential oil for improving nodules as well as preparation method and application of compound essential oil

Abstract

The invention discloses compound essential oil for improving nodules as well as a preparation method and application of the compound essential oil, and relates to the technical field of compound essential oil. Comprising the following raw materials: 0.5-3 parts of radix bupleuri essential oil, 2-5 parts of angelica sinensis essential oil, 2-5 parts of frankincense essential oil, 2-5 parts of myrrh essential oil, 0.5-3 parts of agilawood essential oil, 0.5-5 parts of pericarpium citri reticulatae viride essential oil, 0.5-5 parts of pericarpium citri reticulatae essential oil, 0.5-3 parts of mint essential oil, 0.5-3 parts of helichrysum odoratum essential oil, 0.5-3 parts of liquorice essential oil and 0.5-3 parts of radix ranunculi ternati essential oil. The preparation method of the compound essential oil is simple, low in cost, safe and environment-friendly; the essential oil and the essential oil are mutually coordinated and complement each other, so that the synergistic effect of the curative effect is enhanced; during clinical application, the form is selected from any one of oral preparations of microcapsules, microspheres, fragrant pills and essential oil blasting beads, and external preparations of smearing oil, hydrogel, emulsion, cream, essential oil fragrant pastes or sachets, and is convenient to use.

Description

Technical Field

[0001] The present invention relates to the technical field of compound essential oils, and particularly to a compound essential oil for improving nodules, its preparation method and application. Background Art

[0002] A nodule is a palpable, circumscribed, round, oval or irregular solid skin lesion. Pulmonary nodules, thyroid nodules, breast nodules, liver nodules, etc. are all common nodular diseases. Among them, breast nodules refer to small nodules that occur in the breast. They can be benign or malignant and are clinical manifestations of various breast diseases, such as breast hyperplasia, breast fibroids, breast cancer, etc. The cause of breast nodules is not yet clear and may be related to factors such as changes in hormone levels in the body, gene mutations, and environmental influences. They can occur unilaterally or bilaterally and can exist singly or multiple at the same time. Breast nodules are more common in women over 40 years old. However, the vast majority of breast nodules are benign, and only a very small number will develop into malignant tumors. Therefore, it is crucial to prevent the occurrence and development of breast nodules.

[0003] Currently, the main treatments for breast nodules in Western medicine are surgery and hormone therapy. Among them, surgical treatment is not widely accepted due to issues such as aesthetics, and the surgery only removes the lesion without treating the cause, resulting in a high risk of recurrence; hormone therapy can be used to relieve the symptoms of breast hyperplasia, directly acting on hormone levels to reduce the excessive hyperplasia of breast tissue. However, hormone therapy may also bring some adverse effects, such as it may affect the menstrual cycle, increase the risk of endometriosis, and long-term use may also lead to excessive hyperplasia of the endometrium, making it not suitable for long-term use.

[0004] Breast nodules belong to the categories of "Ru Pi" and "Ru He" in traditional Chinese medicine and are related to factors such as worry, anger, and emotional injury. Traditional Chinese medicine has a long history of understanding Ru Pi and has also accumulated rich treatment experience, creating many effective treatment methods. Chinese medicinal essential oils are volatile aromatic substances extracted from Chinese medicinal materials. They not only have unique aromas but also have various pharmacological effects. The application of Chinese medicinal essential oils is very extensive, including aspects such as relieving mood-related diseases, skin care, antibacterial and anti-inflammatory, and promoting blood circulation. Chinese medicinal essential oils contain high concentrations of active ingredients, have fast drug effects, and strong penetrability. Chinese medicinal essential oils can be directly absorbed through the skin and used through methods such as massage. Therefore, in view of this situation, there is an urgent need to develop a compound essential oil for improving nodules, its preparation method and application to meet the actual usage needs. Summary of the Invention

[0005] In view of this, in view of the deficiencies in the prior art, the main object of the present invention is to provide a compound essential oil for improving nodules, its preparation method and application. The compound essential oil provided by the present invention is a mixture of a variety of single essential oils and plant base oils in proportion; the preparation method of the compound essential oil is simple and the cost is low; the essential oils are coordinated with each other, complementing and enhancing the therapeutic effect; the form in clinical application is selected from any one of microcapsules, microspheres, fragrant pills and essential oil burst bead oral preparations, and external preparations such as rubbing oils, hydrogels, milks, creams, essential oil patches or sachets, which are convenient to use.

[0006] To achieve the above object, the present invention adopts the following technical solutions: A compound essential oil for improving nodules, by weight, comprises the following raw materials: 0.5-3 parts of bupleurum essential oil, 2-5 parts of angelica essential oil, 2-5 parts of frankincense essential oil, 2-5 parts of myrrh essential oil, 0.5-3 parts of agarwood essential oil, 0.5-5 parts of green tangerine peel essential oil, 0.5-5 parts of dried tangerine peel essential oil, 0.5-3 parts of peppermint essential oil, 0.5-3 parts of everlasting essential oil, 0.5-3 parts of liquorice essential oil, 0.5-3 parts of cat's claw grass essential oil.

[0007] As a preferred embodiment: the compound essential oil for improving nodules, by weight, comprises the following raw materials: 3 parts of bupleurum essential oil, 5 parts of angelica essential oil, 5 parts of frankincense essential oil, 5 parts of myrrh essential oil, 2 parts of agarwood essential oil, 5 parts of green tangerine peel essential oil, 5 parts of dried tangerine peel essential oil, 2 parts of peppermint essential oil, 2 parts of everlasting essential oil, 2 parts of liquorice essential oil, 2 parts of cat's claw grass essential oil.

[0008] The preparation method of the compound essential oil for improving nodules comprises the following steps: S1. Separately extract and prepare bupleurum essential oil and angelica essential oil: Crush bupleurum medicinal materials, sieve the crushed bupleurum medicinal materials, place them in a flask, soak them with distilled water, extract them with a volatile oil extractor, assemble the extraction device, set the temperature of the electric heating mantle, extract the bupleurum medicinal materials until the volatile oil amount no longer increases, stop the extraction, dehydrate with anhydrous sodium sulfate, and let it stand to obtain bupleurum volatile oil; Crush angelica medicinal materials, sieve them, place them in a flask, assemble the extraction device, set the temperature of the electric heating mantle, add water to soak, distill and extract, and collect the essential oil to obtain angelica essential oil; S2. Extract and prepare frankincense essential oil: Crush frankincense medicinal materials, sieve them, load them into an extractor for extraction, and collect the extract after the extraction is completed to obtain frankincense essential oil; S3. Extract and prepare myrrh essential oil: Crush myrrh medicinal materials and put them into an extraction kettle. The extraction conditions are: pressure 25 MPa, extraction temperature 45 °C, CO 2 flow rate 100 L / h, analytical kettle temperature 55 °C, extraction time 4 h. The supercritical CO 2After being decompressed and cooled, it is separated from myrrh essential oil. After the extraction is completed, the extract is collected to obtain myrrh essential oil; S4. Preparation of agarwood essential oil: The agarwood wood is crushed to a 40-mesh sieve to obtain powder, soaked in 80% ethanol and sealed, and then extracted in the extraction tank of a subcritical fluid extraction device to obtain agarwood essential oil; S5. Preparation of green tangerine peel essential oil: Take the dried green tangerine peel medicinal material, crush it, pass through a No. 2 sieve, take the medicinal powder and add 8 times the amount of water, control the temperature at 90 - 100 °C, and extract by steam distillation for 6 h. Take the obtained green tangerine peel essential oil from the essential oil collector; S6. Preparation of dried tangerine peel essential oil: Take the dried tangerine peel medicinal powder, add double-distilled water according to the material-liquid ratio of 1:10, extract by steam distillation for 6 h, and take the obtained green tangerine peel essential oil from the essential oil collector; S7. Preparation of peppermint essential oil: Take peppermint medicinal powder and add citric acid buffer solution (1:14, 3.1 m / v) and cellulase for enzymatic hydrolysis, and then distill and extract for 4 h to obtain peppermint essential oil; S8. Preparation of immortelle essential oil: Put dried immortelle flowers in the extraction tank, add 8 times the amount of water, soak for 1 h, keep it boiling gently for 6 h after boiling to obtain immortelle essential oil; S9. Preparation of licorice essential oil: Use subcritical CO 2 to extract licorice essential oil by extraction method. After the licorice is crushed, it is put into the extraction kettle, and the system pressure is reduced to -0.6 MPa by vacuum pumping; Extraction conditions: extraction pressure 7 MPa, separation pressure 5 MPa, extraction temperature 30 °C, separation temperature 50 °C, CO 2 flow rate 30 L / h, extraction time 2 h; Collect the extract, and after drying the oil layer, licorice essential oil is obtained; S10. Preparation of cat's claw herb essential oil: After crushing the cat's claw herb medicinal material, put it into the extraction tank, evacuate to -0.8 MPa, inject butane extractant, and use CO 2 to repeatedly rinse the equipment to remove air, and extract to obtain cat's claw herb essential oil; S11. Preparation of compound essential oil: By weight, 3 parts of bupleurum essential oil, 5 parts of angelica essential oil, 5 parts of frankincense essential oil, 5 parts of myrrh essential oil, 2 parts of agarwood essential oil, 5 parts of green tangerine peel essential oil, 5 parts of dried tangerine peel essential oil, 2 parts of peppermint essential oil, 2 parts of immortelle essential oil, 2 parts of licorice essential oil, and 2 parts of cat's claw herb essential oil are mixed evenly after being dehydrated by anhydrous sodium sulfate to obtain compound essential oil.

[0009] As a preferred scheme: The specific preparation of bupleurum essential oil in step S1 is as follows: Take the bupleurum medicinal material and crush it. Pass the crushed bupleurum medicinal material through a No. 2 sieve, take 5 times the amount of distilled water to soak for 1 h, assemble the extraction device, set the temperature of the electric heating mantle at 320 °C, adjust it to 280 °C after slight boiling, use a volatile oil extractor to extract for 3 h, use anhydrous sodium sulfate for dehydration, and let it stand for 0.5 h to obtain bupleurum volatile oil.

[0010] As a preferred solution: The specific steps for extracting and preparing Angelica essential oil in step S1 are as follows: Crush Angelica medicinal materials, sieve them through a 40-mesh sieve, add 8 times the volume of water, soak for 1.5 h, assemble the extraction device, set the temperature of the electric heating mantle to 320 °C, adjust it to 280 °C after slight boiling, distill and extract for 8 h, and then collect the essential oil to obtain Angelica essential oil.

[0011] As a preferred solution: The conditions for extraction in step S2 are as follows: pressure 30 MPa, extraction temperature 55 °C, CO 2 flow rate 30 L / h, extraction time 2 h. The supercritical CO containing frankincense essential oil 2 is separated from the frankincense essential oil after decompression and cooling.

[0012] As a preferred solution: The extraction conditions in step S4 are as follows: extraction time 6 h, extraction pressure 1.55 MPa, extraction temperature 60 °C.

[0013] As a preferred solution: The conditions for enzymatic hydrolysis in step S7 are as follows: cellulase addition amount 3.18%, enzymatic hydrolysis time 20 h, enzymatic hydrolysis temperature 44 °C.

[0014] As a preferred solution: The ratio of the extraction material of cat's claw herb to butane in step S10 is 1:1.5, extraction temperature 45 °C, extraction pressure 0.8 MPa, extraction time 1 h; collect the extract, and the volatile oil after extraction is centrifuged at 15 °C and 1×10xg for 15 min to remove water.

[0015] The application of the compound essential oil for improving nodules, wherein the form of the compound essential oil in clinical application is selected from any one of oral preparations such as microcapsules, microspheres, fragrant pills, and essential oil bursting beads, and external preparations such as rubbing oils, hydrogels, milks, creams, essential oil patches, and sachets.

[0016] Compared with the prior art, the present invention has obvious advantages and beneficial effects. Specifically, as can be seen from the above technical solutions: First, the present invention mixes essential oils of Bupleurum, Angelica, Frankincense, Myrrh, Aquilaria, Tangerine Peel, Pericarpium Citri Reticulatae Viride, Mentha, Helichrysum, Licorice, and Cat's Claw Herb to prepare a compound essential oil. The active ingredients of each essential oil component are different, and the components act synergistically, which can effectively treat breast nodules, reduce the size of nodules, and relieve the pain caused by nodules. Second, the compound essential oil provided by the present invention combines the advantages of promoting menstruation, activating blood circulation, relieving pain, and regulating yin and yang to adjust functions through massage, which is more easily accepted by patients. At the same time, it is also more conducive to the absorption and diffusion of the essential oil, further improving the curative effect of the compound essential oil. Third, the compound essential oil provided by the present invention can easily penetrate the skin and enter the body through the abundant capillaries under the subcutaneous fat; the compound essential oil is composed of some very small molecules, and these highly volatile substances can be absorbed by the nasal mucosal tissue and enter the body; Fourth, the essential oil provided by the present invention is a compound essential oil, which is a mixture of multiple single essential oils and plant base oils in proportion; the essential oils are coordinated with each other, complement each other, and enhance the synergistic effect of the therapeutic effect; Fifth, the application of an essential oil compound for improving nodules provided by the present invention, in the form of microcapsules, microspheres, fragrant pills and essential oil bursting beads oral preparations, any one of smear oil, hydrogel, lotion, cream, essential oil fragrant patch or fragrant sachet external preparations in clinical application, is convenient to use; Sixth, the preparation method of the compound essential oil provided by the present invention is simple and low-cost.

[0017] In order to more clearly illustrate the structural features and effects of the present invention, it is described in detail below in conjunction with the accompanying drawings and specific embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is a graph showing the effect of the compound essential oil of the present invention on the weight change of HMG rats (n=5, X̅±S); Figure 2 This is a graph showing the effect of the compound essential oil of the present invention on the nipple diameter of HMG rats (n=5, X̅±S; * indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001); Figure 3 This is a graph showing the effect of the compound essential oil of the present invention on the nipple height of HMG rats (n=5, X̅±S; * indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001); Figure 4 The figure shows the effect of the compound essential oil of the present invention on the pathological structure of mammary gland tissue in HMG rats (HE, 50μm, 100×).

[0019] Description of the accompanying drawings: Figure 4 In the figure: A is the blank control group of comparative example 1; B is the model control group of comparative example 2; C is the Rupixiao tablets group of comparative example 3; D is the compound essential oil group of experimental example 1; E is the compound essential oil group of experimental example 2; F is the compound essential oil group of experimental example 3; G is the compound essential oil group of experimental example 4; H is the compound essential oil group of experimental example 5. DETAILED DESCRIPTION

[0020] The present invention Figure 1As shown in Figure 4, a compound essential oil for improving nodules includes the following raw materials, by weight: 0.5-3 parts of bupleurum essential oil, 2-5 parts of angelica essential oil, 2-5 parts of frankincense essential oil, 2-5 parts of myrrh essential oil, 0.5-3 parts of agarwood essential oil, 0.5-5 parts of green peel essential oil, 0.5-5 parts of tangerine peel essential oil, 0.5-3 parts of peppermint essential oil, 0.5-3 parts of immortelle essential oil, 0.5-3 parts of licorice essential oil, and 0.5-3 parts of cat's claw essential oil.

[0021] The compound essential oil for improving nodules comprises the following raw materials by weight: Bupleurum ( Bupleuri Radix ) 3 parts of essential oil, Angelica sinensis ( Angelicae Sinensis Radix ) 5 parts essential oil, frankincense ( Olibanum ) 5 parts essential oil, myrrh ( Myrrha ) 5 parts essential oil, agarwood ( Aquilariae Lignum Resinatum ) 2 parts essential oil, green peel ( Citri Reticulatae Pericarpium Viride ) 5 parts essential oil, tangerine peel ( Citri Reticulatae Pericarpium ) 5 parts essential oil, peppermint ( Menthae Haplocalycis Herba ) 2 parts essential oil, Immortelle ( Xerochrysum bracteatum (Vent.) Tzvelev ) 2 parts essential oil, licorice ( Glycyrrhizae Radix Et Rhizoma ) 2 parts essential oil, cat's claw ( Ranunculi Ternati Radix ) 2 parts essential oil.

[0022] Bupleurum Bupleuri Radix ): It is a plant of the Umbelliferae family. Its main components are saikosaponin, sterols, volatile oils (bupleurol, eugenol, etc.), fatty acids (oleic acid, linoleic acid, palmitic acid, stearic acid, etc.) and polysaccharides. It has a slight fragrance and can regulate liver qi, relieve liver qi and depression. It can be used to treat chest and rib distension and pain caused by liver qi stagnation, emotional depression, etc.

[0023] Angelica Angelicae Sinensis Radix ): It is a plant of the Umbelliferae family, mainly containing n-butenoyl lactone, niacin, etc. This product has a strong aroma and has the effect of nourishing blood and activating blood circulation.

[0024] mastic( Olibanum ): It is a plant of the genus Frankincense in the family Oleaceae. It mainly contains frankincense fatty acid, frankincense hydrocarbons, frankincense secondary acid, frankincense acid, etc. It has a specific aroma, can promote blood circulation and qi, disperse nodules and relieve pain, reduce swelling and promote tissue regeneration, and can treat scrofula, phlegm nodules, and hard lumps that do not disappear, such as thyroid nodules, breast nodules, etc.

[0025] Myrrh Myrrha ): A plant of the olive family, it contains substances such as α-pinene and D-limonene. These ingredients have a pure, round, sweet and elegant smell and have the effects of dispersing blood stasis, relieving pain, reducing swelling and promoting tissue regeneration.

[0026] Agarwood Aquilariae Lignum Resinatum):A plant of the genus Aquilaria in the family Thymelaeaceae. Its main components include sesquiterpenoids, 2-(2-phenylethyl)chromones, small molecular aromatic substances, fatty acid compounds, etc. As one of the commonly used essential oils in aromatherapy, it has pharmacological activities such as antioxidant, antibacterial, sedative, anti-inflammatory, and anti-cancer, and also has the effects of promoting qi flow to relieve pain and calming the mind and soothing the nerves.

[0027] Qingpi ( Citri Reticulatae Pericarpium Viride ):A plant of the family Rutaceae. Its essential oil mainly contains D-limonene and has the effects of dispersing the stagnated liver qi and resolving food stagnation.

[0028] Chenpi ( Citri Reticulatae Pericarpium ):A plant of the family Rutaceae. Its essential oil mainly contains compounds such as D-limonene, γ-terpinene, β-myrcene, and α-pinene, and has pharmacological activities such as antibacterial, anti-inflammatory, anti-tumor, anti-asthmatic and cough-suppressing. It has the effects of strengthening the spleen and regulating qi, promoting qi flow to relieve pain. The components in Chenpi essential oil have the effect of inhibiting the central nervous system. Some compounds in Chenpi essential oil can regulate the balance of neurotransmitters in the brain and improve the emotional state. Some substances in Chenpi essential oil can inhibit the activation of inflammatory cells and the release of inflammatory mediators, and treat nodules.

[0029] Mentha haplocalyx Briq. ( Menthae Haplocalycis Herba ):The dried aerial part of the plant Mentha haplocalyx Briq. of the genus Mentha in the family Lamiaceae has the effects of inducing sweating and relieving fever, soothing the liver and regulating qi, relieving sore throat and itching. It has a cooling effect on the body, so it also has the effects of anti-inflammatory and analgesic, and dispersing wind-heat.

[0030] Helichrysum bracteatum (Vent.) Andr. ( Xerochrysum bracteatum (Vent.) Tzvelev ):A perennial herb of the family Asteraceae, and has the effects of dispersing wind and clearing heat, clearing heat and detoxifying.

[0031] Glycyrrhiza uralensis Fisch. ( Glycyrrhizae Radix Et Rhizoma ):It is sweet and flat, and its medicinal properties are mild. When used together with various drugs of cold, heat, tonifying and purging, it can alleviate the pungency or reduce the toxic and side effects, and has the function of coordinating all medicines, so it is known as the "national old". In addition, Glycyrrhiza uralensis Fisch. has a certain detoxifying effect on poisoning caused by drugs or foods.

[0032] Ranunculus ternatus Thunb. ( Ranunculi Ternati Radix ):The tuberous roots of the plant Ranunculus ternatus Thunb. of the genus Ranunculus in the family Ranunculaceae, sweet and pungent in taste, slightly warm in nature, and have the effects of resolving phlegm and dissipating nodules, detoxifying and detumescence.

[0033] The preparation method of the compound essential oil for improving nodules includes the following steps: S1. Extract Bupleurum essential oil and Angelica essential oil respectively: Crush the Bupleurum medicinal materials, sieve the crushed Bupleurum medicinal materials, place them in a flask, soak them with distilled water, extract using a volatile oil extractor, assemble the extraction device, set the temperature of the electric heating mantle, extract the Bupleurum medicinal materials until the amount of volatile oil no longer increases, stop the extraction, dehydrate with anhydrous sodium sulfate, and let it stand to obtain Bupleurum volatile oil; Crush the Angelica medicinal materials, sieve them, place them in a flask, assemble the extraction device, set the temperature of the electric heating mantle, add water to soak, distill and extract, and collect the essential oil to obtain Angelica essential oil; S2. Extract and prepare Frankincense essential oil: Crush the Frankincense medicinal materials, sieve them, load them into an extractor for extraction, and collect the extract after the extraction ends to obtain Frankincense essential oil; S3. Extract and prepare Myrrh essential oil: Crush the Myrrh medicinal materials and put them into an extraction kettle. The extraction conditions are: pressure 25 MPa, extraction temperature 45 °C, CO 2 flow rate 100 L / h, analytical kettle temperature 55 °C, extraction time 4 h. The supercritical CO 2 containing Myrrh essential oil is separated from the Myrrh essential oil after decompression and cooling, and the extract is collected after the extraction ends to obtain Myrrh essential oil; S4. Prepare Aquilaria essential oil: Crush the Aquilaria wood to 40-mesh sieve to obtain powder, soak it with 80% ethanol and seal it, place it in the extraction tank of a subcritical fluid extraction device for extraction, and obtain Aquilaria essential oil; S5. Prepare Pericarpium Citri Reticulatae Viride essential oil: Take the dried Pericarpium Citri Reticulatae Viride medicinal materials, crush them, sieve them through a No. 2 sieve, take the medicinal powder and add 8 times the amount of water, control the temperature at 90 - 100 °C, and extract by steam distillation for 6 h. Take the obtained Pericarpium Citri Reticulatae Viride essential oil from the essential oil collector; S6. Take the Pericarpium Citri Reticulatae powder, add double-distilled water according to the solid-liquid ratio of 1:10, extract by steam distillation for 6 h, and take the obtained Pericarpium Citri Reticulatae essential oil from the essential oil collector; S7. Prepare Mentha haplocalyx Briq. essential oil: Take Mentha haplocalyx Briq. powder, add citric acid buffer solution (1:14, 3.1 m / v) and cellulase for enzymatic hydrolysis, and then distill and extract for 4 h to obtain Mentha haplocalyx Briq. essential oil; S8. Prepare Helichrysum italicum essential oil: Place the dried Helichrysum italicum flowers in an extraction tank, add 8 times the amount of water, soak for 1 h, keep it boiling gently for 6 h after boiling to obtain Helichrysum italicum essential oil; S9. Prepare Glycyrrhiza glabra essential oil: Extract Glycyrrhiza glabra essential oil by subcritical CO 2 extraction method. After crushing Glycyrrhiza glabra, put it into the extraction kettle, evacuate to make the system pressure drop to -0.6 MPa; Extraction conditions: extraction pressure 7 MPa, separation pressure 5 MPa, extraction temperature 30 °C, separation temperature 50 °C, CO 2 flow rate 30 L / h, extraction time 2 h; Collect the extract, and the oil layer is dried to obtain Glycyrrhiza glabra essential oil; S10. Preparation of cat's claw essential oil: The cat's claw medicinal materials are crushed and loaded into an extraction tank. The vacuum is pumped to -0.8 MPa, and butane extractant is injected. Use CO 2 Rinse the equipment repeatedly to remove air, and extract to obtain cat's claw essential oil; S11. Preparation of compound essential oil: By weight, 3 parts of bupleurum essential oil, 5 parts of angelica essential oil, 5 parts of frankincense essential oil, 5 parts of myrrh essential oil, 2 parts of agarwood essential oil, 5 parts of green tangerine peel essential oil, 5 parts of dried tangerine peel essential oil, 2 parts of peppermint essential oil, 2 parts of everlasting essential oil, 2 parts of licorice essential oil, and 2 parts of cat's claw essential oil are mixed evenly after dehydration with anhydrous sodium sulfate to obtain compound essential oil.

[0034] The specific method for extracting and preparing bupleurum essential oil in step S1 is as follows: The bupleurum medicinal materials are crushed, passed through a No. 2 sieve, placed in a round-bottomed flask, soaked in 5 times the amount of distilled water for 1 h, and extracted with a volatile oil extractor for 3 h. Assemble the extraction device, set the temperature of the electric heating mantle to 320 °C, adjust it to 280 °C after slight boiling, and extract the bupleurum medicinal materials until the amount of volatile oil no longer increases. Stop the extraction, dehydrate with anhydrous sodium sulfate, and let it stand for 0.5 h to obtain bupleurum volatile oil.

[0035] The specific method for extracting and preparing angelica essential oil in step S1 is as follows: The angelica medicinal materials are crushed, passed through a 40-mesh sieve, placed in a round-bottomed flask, assemble the extraction device, set the temperature of the electric heating mantle to 320 °C, adjust it to 280 °C after slight boiling, add 8 times the volume of water, soak for 1.5 h, and collect the essential oil after distillation extraction for 8 h to obtain angelica essential oil.

[0036] The extraction conditions in step S2 are: pressure 30 MPa, extraction temperature 55 °C, CO 2 flow rate 30 L / h, extraction time 2 h. The supercritical CO containing frankincense essential oil 2 is separated from the frankincense essential oil after decompression and temperature reduction.

[0037] The extraction conditions in step S4 are: extraction time 6 h, extraction pressure 1.55 MPa, extraction temperature 60 °C.

[0038] The enzymatic hydrolysis conditions in step S7 are: cellulase addition amount 3.18%, enzymatic hydrolysis time 20 h, enzymatic hydrolysis temperature 44 °C.

[0039] The ratio of the cat's claw herb to butane in the extraction liquid in step S10 is 1:1.5, the extraction temperature is 45 °C, the extraction pressure is 0.8 MPa, and the extraction time is 1 h; collect the extract, and the volatile oil after extraction is centrifuged at 15 °C and 1×10xg for 15 min to remove water.

[0040] Application of the compound essential oil for improving nodules. The form of the compound essential oil in clinical application is selected from any one of oral preparations such as microcapsules, microspheres, fragrant pills, and essential oil bursting beads, and external preparations such as spreading oils, hydrogels, milks, creams, essential oil patches, and sachets.

[0041] Experimental Example 1: A compound essential oil for improving nodules By weight, it includes the following raw materials: 3 parts of Bupleurum chinense essential oil, 5 parts of Angelica sinensis essential oil, 5 parts of Boswellia carterii essential oil, 5 parts of Commiphora myrrha essential oil, 2 parts of Aquilaria sinensis essential oil, 5 parts of Citrus reticulata Blanco var. austera essential oil, 5 parts of Citrus reticulata Blanco essential oil, 2 parts of Mentha haplocalyx Briq. essential oil, 2 parts of Helichrysum bracteatum essential oil, 2 parts of Glycyrrhiza glabra essential oil, 2 parts of Ranunculus ternatus Thunb. essential oil.

[0042] Take 5 female SD rats weighing 200±20 g, raise them normally for 7 days, and use exogenous estradiol benzoate and progesterone to jointly establish a rat model of mammary gland hyperplasia. The rats are intramuscularly injected with estradiol benzoate injection at 0.5 mg·kg -1 , once a day for 25 consecutive days, and then intramuscularly injected with progesterone injection at 5 mg·kg -1 , once a day for 5 consecutive days. After 7 days of modeling, prepare the compound essential oil and administer it by gavage. It is diluted with polyoxyethylene hydrogenated castor oil and normal saline, the volatile oil content is 5%, and the dosage is about 2 ml / rat for 30 consecutive days.

[0043] Experimental Example 2: A compound essential oil for improving nodules By weight, it includes the following raw materials: 2 parts of Bupleurum chinense essential oil, 3 parts of Angelica sinensis essential oil, 3 parts of Boswellia carterii essential oil, 3 parts of Commiphora myrrha essential oil, 2 parts of Aquilaria sinensis essential oil, 3 parts of Citrus reticulata Blanco var. austera essential oil, 3 parts of Citrus reticulata Blanco essential oil, 2 parts of Mentha haplocalyx Briq. essential oil, 2 parts of Helichrysum bracteatum essential oil, 2 parts of Glycyrrhiza glabra essential oil, 2 parts of Ranunculus ternatus Thunb. essential oil.

[0044] Take 5 female SD rats weighing 200±20 g, raise them normally for 7 days, and use exogenous estradiol benzoate and progesterone to jointly establish a rat model of mammary gland hyperplasia. The rats are intramuscularly injected with estradiol benzoate injection at 0.5 mg·kg -1 , once a day for 25 consecutive days, and then intramuscularly injected with progesterone injection at 5 mg·kg -1 , once a day for 5 consecutive days. After 7 days of modeling, prepare the compound essential oil and administer it by gavage. It is diluted with polyoxyethylene hydrogenated castor oil and normal saline, the volatile oil content is 5%, and the dosage is about 2 ml / rat for 30 consecutive days.

[0045] Experimental Example 3: A compound essential oil for improving nodules By weight, it includes the following raw materials: 1 part of Bupleurum chinense essential oil, 2 parts of Angelica sinensis essential oil, 2 parts of Boswellia carterii essential oil, 2 parts of Commiphora myrrha essential oil, 2 parts of Aquilaria sinensis essential oil, 2 parts of Citrus reticulata Blanco var. austera essential oil, 2 parts of Citrus reticulata Blanco essential oil, 2 parts of Mentha haplocalyx Briq. essential oil, 2 parts of Helichrysum bracteatum essential oil, 2 parts of Glycyrrhiza glabra essential oil, 2 parts of Ranunculus ternatus Thunb. essential oil.

[0046] Five female SD rats weighing 200 ± 20 g were taken and normally raised for 7 days. An exogenous estradiol benzoate and progesterone combination was used to replicate a rat model of mammary gland hyperplasia. The rats were intramuscularly injected with estradiol benzoate injection at a dose of 0.5 mg·kg -1 , once a day for 25 consecutive days. Then, they were given intramuscular injection of progesterone injection at a dose of 5 mg·kg -1 , once a day for 5 consecutive days. After 7 days of model establishment, a compound essential oil was prepared and administered by gavage. It was diluted with polyoxyethylene hydrogenated castor oil and normal saline, with the volatile oil content being 5%, and the dosage was about 2 ml / rat, for 30 consecutive days.

[0047] Experimental Example 4: Five female SD rats weighing 200 ± 20 g were taken and normally raised for 7 days. An exogenous estradiol benzoate and progesterone combination was used to replicate a rat model of mammary gland hyperplasia. The rats were intramuscularly injected with estradiol benzoate injection at a dose of 0.5 mg·kg -1 , once a day for 25 consecutive days. Then, they were given intramuscular injection of progesterone injection at a dose of 5 mg·kg -1 , once a day for 5 consecutive days.

[0048] The compound essential oil was prepared according to Experimental Example 1. In the compound essential oil group, it was administered by topical application, with the dosage being about 0.2 ml / rat, for 30 consecutive days; it was applied to the 2nd and 3rd pairs of nipples, massaged for 10 s after application, and fixed with a sterile dressing for 30 min.

[0049] Experimental Example 5: Five female SD rats weighing 200 ± 20 g were taken and normally raised for 7 days. An exogenous estradiol benzoate and progesterone combination was used to replicate a rat model of mammary gland hyperplasia. The rats were intramuscularly injected with estradiol benzoate injection at a dose of 0.5 mg·kg -1 , once a day for 25 consecutive days. Then, they were given intramuscular injection of progesterone injection at a dose of 5 mg·kg -1 , once a day for 5 consecutive days.

[0050] The compound essential oil was prepared according to Experimental Example 1. In the compound essential oil group, it was administered by topical application, with the dosage being about 0.4 ml / rat, for 30 consecutive days; it was applied to the 2nd and 3rd pairs of nipples, massaged for 10 s after application, and fixed with a sterile dressing for 30 min.

[0051] Comparative Example 1 (blank control group): Five female SD rats weighing 200 ± 20 g were taken and normally raised for 44 days.

[0052] Comparative Example 2 (model control group): Female SD rats weighing 200 ± 20 g were taken and normally raised for 7 days. An exogenous estradiol benzoate and progesterone combination was used to replicate a rat model of mammary gland hyperplasia. The rats were intramuscularly injected with estradiol benzoate injection at a dose of 0.5 mg·kg -1 , once a day for 25 consecutive days. Then, they were given intramuscular injection of progesterone injection at a dose of 5 mg·kg -1, once a day for 5 consecutive days; 7 days after modeling, the base oil (almond oil) was given by gavage. It was diluted and prepared with polyoxyethylene hydrogenated castor oil and normal saline, with the volatile oil content of 5%, and the dosage was about 2 ml / rat for 30 consecutive days.

[0053] Control Group 3 (Ru Pixiao Tablet Control Group): 200 ± 20 g female SD rats were taken and normally fed for 7 days. An exogenous estradiol benzoate and progesterone combined method was used to replicate the mammary hyperplasia rat model. The rats were intramuscularly injected with estradiol benzoate injection at a dose of 0.5 mg·kg -1 , once a day for 25 consecutive days, and then intramuscularly injected with progesterone injection at a dose of 5 mg·kg -1 , once a day for 5 consecutive days; after the model was successfully established, Ru Pixiao tablet suspension was given by gavage, and the dosage was 0.5 g / kg / d, which was a suspension prepared with normal saline.

[0054] Detection: (1) Detection of rat body weight: After modeling and drug intervention, the body weights of rats in each group were weighed once a week.

[0055] (2) Detection of rat breast appearance: The color and size of the breasts were observed daily. After the last administration, the rats were fasted for 12 h. After anesthesia, the nipple diameters of the second pair of breasts of each rat were measured with a vernier caliper.

[0056] (3) Blood was taken from the abdominal aorta, left to stand for 2 h, centrifuged at 4500 r / min for 10 min, and the serum was taken. The levels of serum E2, P, and PRL were measured by enzyme-linked immunosorbent assay according to the kit instructions.

[0057] (4) Then the second pair of intact breasts was removed, fixed with 4% paraformaldehyde solution, routinely sectioned, HE stained, and the mammary gland tissues such as lobular acini and ductal epithelial hyperplasia were observed and analyzed under the microscope.

[0058] Experimental results: 1. In this experiment, it was observed that there were significant differences in the body weight gain of rats in different treatment groups. The animals in the blank control group showed normal body weight accumulation during the experimental period. In contrast, the body weight gain rate of the animals in the model control group was significantly lower than that of other groups, indicating that the successful establishment of the mammary hyperplasia disease model might cause metabolic disorders in the rat body. The compound essential oil intervention groups (Experimental Examples 1 - 5) as a whole showed a better body weight gain trend than the model control group.

[0059] 2. Measuring the diameter and height of the nipple with a vernier caliper, it was found that the model control group showed significant hyperplastic changes in breast tissue compared with the blank control group, manifested as pathological enlargement of the nipple diameter and height. The compound essential oil intervention group as a whole showed an inhibitory effect on breast tissue hyperplasia. Among them, Experimental Example 1 showed the best improvement effect in the ratio optimization group (Experimental Examples 1 - 3), and its nipple diameter and height both decreased to the lowest level. In the comparison group of administration methods, the intervention effect of the external application group (Experimental Examples 4 and 5) was significantly better than that of the oral gavage group (Experimental Example 1), suggesting that transdermal administration of essential oil may have better bioavailability.

[0060] 3. Measuring serum sex hormones by Elisa: The Elisa test results showed that the model control group had characteristic sex hormone disorders compared with the blank control group: the level of progesterone (P) decreased significantly, while the levels of estradiol (E2) and prolactin (PRL) increased abnormally, which was consistent with the pathological mechanism of mammary gland hyperplasia. The compound essential oil intervention group could effectively reverse the hormone imbalance state, manifested as the increase in P level and the decrease in E2 and PRL levels. In the investigation of the ratio optimization of Experimental Examples 1 - 3, the increase in P level and the decrease in E2 and PRL levels in Experimental Example 1 were the most obvious, and the hormone regulation effect was the most significant; while in the investigation of the administration methods of Experimental Examples 1, 4, and 5, the external administration in Experimental Example 4 achieved the best regulation effect, indicating that the compound essential oil can regulate the function of the hypothalamus - pituitary - gonadal axis through multiple targets, and the best ratio and the external administration method can have a synergistic effect.

[0061] Table 1 Effects of compound essential oil on the levels of E2, P, and PRL in the serum of HMG rats (n = 5, X̅±S)

[0062] Note: Compared with the blank group, *P < 0.05; compared with the model group, #P < 0.05.

[0063] 4. Results of pathological sections ( Figure 4 ): Compared with the blank control group of Comparative Example 1, in the mammary gland tissue of rats in the model control group of Comparative Example 2, the alveoli were irregular in shape, the secretions increased, and the cells proliferated significantly; compared with the model control group of Comparative Example 2, in the mammary gland tissue of rats in the Rupixiao tablet group of Comparative Example 3 and the compound essential oil group in Experimental Example 1, the alveoli were regular in shape, the secretions decreased, and the degree of cell proliferation was reduced; compared with the Rupixiao tablet group of Comparative Example 3, in the mammary gland tissue of rats in the compound essential oil group in Experimental Example 1, the alveoli were relatively regular in shape, the secretions decreased, and the degree of proliferation of mammary gland cells was reduced.

[0064] The design focus of the present invention lies in: First, the present invention uses a compound essential oil prepared by mixing essential oils of Bupleuri Radix, Angelicae Sinensis Radix, Olibanum, Myrrha, Aquilariae Lignum Resinatum, Citri Reticulatae Viride Pericarpium, Citri Reticulatae Pericarpium, Menthae Haplocalycis Herba, Helichrysi Flos, Glycyrrhizae Radix et Rhizoma, and Radix Ranunculi Ternati. The active ingredients of each essential oil component are different, and each component acts synergistically to effectively treat breast nodules, reduce the size of nodules, and relieve pain caused by nodules. Second, the compound essential oil provided by the present invention combines the advantages of dredging meridians, promoting blood circulation, relieving pain, and regulating yin and yang to adjust functions through massage, which is more easily accepted by patients. At the same time, it is also more conducive to the absorption and diffusion of essential oils, further improving the curative effect of the compound essential oil. Third, the compound essential oil provided by the present invention is extremely easy to penetrate the skin and can enter the body through the rich capillaries under the subcutaneous fat. The compound essential oil is composed of some very small molecules, and these highly volatile substances can be absorbed by the nasal mucosa tissue and enter the body. Fourth, the essential oil provided by the present invention is a compound essential oil, which is a mixture of various single essential oils and plant base oils in a certain proportion. The essential oils are coordinated with each other, and they complement and enhance each other's curative effects through synergistic effects. Fifth, the present invention provides an application of an essential oil compound for improving nodules. The form in clinical application is selected from any one of microcapsules, microspheres, fragrant pills, and essential oil burst beads oral preparations, as well as external preparations such as rubbing oils, hydrogels, milks, creams, essential oil patches, or sachets, which is convenient to use. Sixth, the preparation method of the compound essential oil provided by the present invention is simple and the cost is low.

[0065] The above is only a preferred embodiment of the present invention, and it does not limit the technical scope of the present invention. Therefore, any minor modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A compound essential oil for improving nodules, characterized in that: The raw materials are included by weight: 0.5-3 parts of bupleurum essential oil, 2-5 parts of angelica essential oil, 2-5 parts of frankincense essential oil, 2-5 parts of myrrh essential oil, 0.5-3 parts of agarwood essential oil, 0.5-5 parts of green peel essential oil, 0.5-5 parts of tangerine peel essential oil, 0.5-3 parts of peppermint essential oil, 0.5-3 parts of immortelle essential oil, 0.5-3 parts of licorice essential oil, and 0.5-3 parts of cat's claw essential oil.

2. The compound essential oil for improving nodules according to claim 1, characterized in that: Calculated by weight, the following raw materials are included: 3 parts of bupleurum essential oil, 5 parts of angelica essential oil, 5 parts of frankincense essential oil, 5 parts of myrrh essential oil, 2 parts of agarwood essential oil, 5 parts of green peel essential oil, 5 parts of tangerine peel essential oil, 2 parts of peppermint essential oil, 2 parts of immortelle essential oil, 2 parts of licorice essential oil, and 2 parts of cat's claw essential oil.

3. A method for preparing a compound essential oil for improving nodules as described in any one of claims 1-2, characterized in that: The steps include: S1. Extract and prepare Bupleurum essential oil and Angelica essential oil respectively: grind Bupleurum medicinal material, sieve the grinded Bupleurum medicinal material, place it in a flask, soak it in distilled water, extract it using a volatile oil extractor, assemble an extraction device, set the temperature of the electric heating jacket, extract the Bupleurum medicinal material until the amount of volatile oil no longer increases, stop extracting, dehydrate it with anhydrous sodium sulfate, let it stand, and obtain Bupleurum volatile oil; grind Angelica medicinal material, sieve it, place it in a flask, assemble an extraction device, set the temperature of the electric heating jacket, add water to soak it, collect the essential oil after distillation and extraction, and obtain Angelica essential oil; S2, extracting and preparing frankincense essential oil: crushing frankincense medicinal materials, sieving, loading into an extractor for extraction, collecting the extract after the extraction is completed, and obtaining frankincense essential oil; S3, extracting and preparing myrrh essential oil: taking myrrh medicinal materials and grinding them, putting them into an extraction kettle, the extraction conditions are: pressure 25MPa, extraction temperature 45°C, CO2 flow rate 100L / h, desorption kettle temperature 55°C, extraction time 4h, supercritical CO2 containing myrrh essential oil is separated from myrrh essential oil after decompression and cooling, and the extract is collected after the extraction is completed to obtain myrrh essential oil; S4, preparing agarwood essential oil: grinding agarwood wood into a 40-mesh sieve to obtain powder, soaking it in 80% ethanol and sealing it, and extracting it in an extraction tank of a subcritical fluid extraction device to obtain agarwood essential oil; S5, preparing Qingpi essential oil: taking dried Qingpi medicinal material, crushing, passing through No. 2 sieve, taking the powder and adding 8 times of water, controlling the temperature at 90-100°C, extracting by steam distillation for 6h, and taking the obtained Qingpi essential oil from the essential oil collector; S6, preparing tangerine peel essential oil: taking crushed tangerine peel, adding double distilled water according to a solid-liquid ratio of 1:10, extracting by steam distillation for 6h, and taking the obtained tangerine peel essential oil from the essential oil collector; S7, preparing peppermint essential oil: taking peppermint powder, adding citric acid buffer (1:14, 3.1 m / v) and cellulase for enzymolysis, and then distilling and extracting for 4 hours to obtain peppermint essential oil; S8, preparing immortelle essential oil: placing dried immortelle flowers in an extraction tank, adding 8 times the amount of water, soaking for 1 hour, and then boiling and maintaining a slightly boiling state for 6 hours to obtain immortelle essential oil; S9, preparation of licorice essential oil: extracting licorice essential oil by subcritical CO2 extraction method, crushing licorice and putting it into extraction kettle, evacuating the system pressure to -0.6MPa; extraction conditions: extraction pressure 7MPa, separation pressure 5MPa, extraction temperature 30°C, separation temperature 50°C, CO2 flow rate 30L / h, extraction time 2h; collecting the extract, and obtaining licorice essential oil after the oil layer is dried; S10, preparing cat's claw essential oil: taking cat's claw herbs and crushing them into an extraction tank, evacuating to -0.8 MPa, injecting butane extractant, repeatedly flushing the equipment with CO2 to remove air, and extracting cat's claw essential oil; S11. Preparation of compound essential oil: by weight, 3 parts of bupleurum essential oil, 5 parts of angelica essential oil, 5 parts of frankincense essential oil, 5 parts of myrrh essential oil, 2 parts of agarwood essential oil, 5 parts of green peel essential oil, 5 parts of tangerine peel essential oil, 2 parts of peppermint essential oil, 2 parts of helichrysum essential oil, 2 parts of licorice essential oil and 2 parts of cat's claw essential oil are mixed uniformly after dehydration with anhydrous sodium sulfate to obtain a compound essential oil.

4. The preparation method of the compound essential oil for improving tubercle according to claim 3, characterized in that: The step S1 of extracting and preparing bupleurum essential oil specifically comprises: grinding bupleurum medicinal material, passing the ground bupleurum medicinal material through a No. 2 sieve, soaking it in 5 times the amount of distilled water for 1 hour, assembling an extraction device, setting the temperature of the electric heating jacket at 320° C., adjusting the temperature to 280° C. after slight boiling, extracting it with a volatile oil extractor for 3 hours, dehydrating it with anhydrous sodium sulfate, and letting it stand for 0.5 hour to obtain bupleurum volatile oil.

5. The preparation method of the compound essential oil for improving tubercle according to claim 3, characterized in that: The step S1 of extracting and preparing angelica essential oil specifically comprises: taking angelica medicinal materials, grinding them, passing through a 40-mesh sieve, adding 8 times the volume of water, soaking for 1.5 hours, assembling an extraction device, setting the temperature of the electric heating jacket at 320° C., adjusting the temperature to 280° C. after slight boiling, and collecting the essential oil after distillation extraction for 8 hours to obtain angelica essential oil.

6. The preparation method of the compound essential oil for improving tubercle according to claim 3, characterized in that: The extraction conditions in step S2 are: pressure 30 MPa, extraction temperature 55° C., CO2 flow rate 30 L / h, extraction time 2 h, and the supercritical CO2 containing frankincense essential oil is separated from the frankincense essential oil after decompression and cooling.

7. The preparation method of the compound essential oil for improving tubercle according to claim 3, characterized in that: The extraction conditions in step S4 are: extraction time 6 hours, extraction pressure 1.55 MPa, and extraction temperature 60°C.

8. The preparation method of the compound essential oil for improving tubercle according to claim 3, characterized in that: The conditions for enzymatic hydrolysis in step S7 are: 3.18% cellulase addition, 20 hours of enzymatic hydrolysis time, and 44° C. of enzymatic hydrolysis temperature.

9. The preparation method of the compound essential oil for improving tubercle according to claim 3, characterized in that: In the step S10, the extraction liquid ratio of cat's claw herb to butane is 1:1.5, the extraction temperature is 45°C, the extraction pressure is 0.8MPa, and the extraction time is 1h; the extract is collected, and the extracted volatile oil is centrifuged at 15°C and 1×10×g for 15min to remove water.

10. An application of the compound essential oil for improving nodules according to any one of claims 1 to 2, characterized in that: The compound essential oil is in the form of oral preparations of microcapsules, microspheres, fragrant pills, essential oil burst beads, any one of external preparations of smear oil, hydrogel, lotion, cream, essential oil fragrant patch, and fragrant sachet during clinical application.

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