Traditional Chinese medicine composition and traditional Chinese medicine compound essential oil for relieving side effects of chemotherapy as well as preparation method and application of traditional Chinese medicine compound essential oil

Abstract

The invention provides a traditional Chinese medicine composition for relieving chemotherapy side effects, traditional Chinese medicine compound essential oil and a preparation method and application thereof, and relates to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 1-9 parts of pericarpium citri reticulatae, 1-9 parts of pericarpium citri reticulatae viride, 1-9 parts of clove, 1-9 parts of fennel, 1-9 parts of ginger, 1-9 parts of pogostemon cablin and 1-9 parts of rhizoma atractylodis. The traditional Chinese medicine composition is mainly used for treating abdominal distension pain, nausea and vomiting caused by damp turbidity resistance and spleen and stomach disharmony through the effects of promoting qi circulation, removing dampness, strengthening the spleen and harmonizing the stomach. Experimental results show that the traditional Chinese medicine compound essential oil prepared from the traditional Chinese medicine composition can reduce allotriophagia behaviors of rats and improve ingestion and drinking habits, has a recovery effect on metabolite disorder caused by chemotherapy-related nausea and vomiting, and provides a theoretical basis for a supplementary treatment method of chemotherapy-related nausea and vomiting.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and in particular relates to a traditional Chinese medicine composition for alleviating the side effects of chemotherapy, a traditional Chinese medicine compound essential oil, and a preparation method and application thereof. Background Art

[0002] Chemotherapy-induced nausea and vomiting (CINV) is one of the most common adverse reactions during chemotherapy for cancer patients, and is also one of the important reasons why many cancer patients fear chemotherapy. Although major breakthroughs have been made in the treatment of CINV, it is still very common in actual clinical practice, with the incidence of nausea and vomiting still as high as 61% and 25%, respectively. CINV has a significant impact on the lives of patients. It is not only prone to anxiety, malnutrition, and gastric damage, but also causes anxiety and fear of chemotherapy in patients. Anticipatory nausea and vomiting is likely to occur during chemotherapy again, thus affecting the overall health of patients and the treatment effect.

[0003] Studies have shown that CINV is caused by the release of multiple classic emetic neurotransmitters (such as histamine, 5-hydroxytryptamine, cortisol, etc.) by cytotoxic drugs (such as cisplatin, etc.) through enterochromaffin cells and / or sensory neurons in the gastrointestinal tract and the central nervous system. Currently, the main treatment guideline is to block neurotransmitter receptors. Triple antiemetic therapy (5-hydroxytryptamine receptor blocker and neurokinin 1 receptor blocker plus corticosteroid dexamethasone) is currently a preventive antiemetic therapy for acute and delayed vomiting caused by highly emetogenic chemotherapy regimens, but it has not yet achieved complete vomiting protection for all cancer patients, and the damage caused by antiemetic drugs to the human body is unavoidable. However, traditional Chinese medicine theory believes that vomiting is caused by the loss of harmony and descent of the stomach and the upward reversal of qi. Its concept of conditioning and neutralization has unique advantages in the treatment of emesis. Among them, aromatherapy is expected to supplement and replace current antiemetic medical methods due to its significant effects in relieving symptoms such as pain, nausea, and anxiety. Summary of the invention

[0004] In view of this, the object of the present invention is to provide a Chinese medicine composition for alleviating the side effects of chemotherapy. The Chinese medicine composition treats abdominal distension and pain and nausea and vomiting caused by dampness and turbidity blocking the middle part of the body and disharmony between the spleen and stomach through the effects of promoting qi and eliminating dampness, strengthening the spleen and harmonizing the stomach.

[0005] Another object of the present invention is to provide a Chinese herbal compound essential oil for relieving the side effects of chemotherapy, and a preparation method and application thereof, wherein the Chinese herbal compound essential oil shows potential efficacy in relieving CINV.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The invention provides a traditional Chinese medicine composition for relieving the side effects of chemotherapy. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 1-9 parts of tangerine peel, 1-9 parts of green peel, 1-9 parts of cloves, 1-9 parts of fennel, 1-9 parts of ginger, 1-9 parts of patchouli, and 1-9 parts of atractylodes.

[0008] The present invention also provides a traditional Chinese medicine compound essential oil for alleviating the side effects of chemotherapy. The traditional Chinese medicine compound essential oil comprises the traditional Chinese medicine composition.

[0009] The present invention also provides a preparation method of the traditional Chinese medicine compound essential oil, comprising the following steps: extracting tangerine peel, green peel, clove, fennel, ginger, patchouli and atractylodes lancea by steam distillation to obtain tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes lancea essential oil, respectively, and then mixing the traditional Chinese medicine essential oils obtained by the extraction to obtain the traditional Chinese medicine compound essential oil.

[0010] Preferably, the extraction time of the steam distillation method is 1 to 5 hours.

[0011] Preferably, the mass volume ratio of the traditional Chinese medicine to water during extraction by the steam distillation method is 1:25 to 35.

[0012] Preferably, the tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are mixed in a volume ratio of 1-10:1-10:1-10:1-10:1-10:1-10:1-10:1-10:1-10.

[0013] Preferably, the distillation temperature of the steam distillation method is 95-100°C.

[0014] The present invention also provides an application of the Chinese medicine composition or the Chinese medicine compound essential oil in preparing a medicine for alleviating and / or treating the side effects of chemotherapy.

[0015] Preferably, the side effects include nausea and vomiting reactions occurring during chemotherapy and / or chemotherapy drug treatment.

[0016] Preferably, the chemotherapy drugs include one or more of cisplatin, dacarbazine, nitrogen mustard and cyclophosphamide.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] (1) The present invention provides a Chinese medicine composition for relieving the side effects of chemotherapy. In the composition, green peel enters the liver and gallbladder, promotes qi on the left and ascends; tangerine peel enters the spleen and lungs, promotes qi on the right and descends, and the ascending and descending are coordinated, breaking qi and resolving phlegm, and playing the role of soothing the liver and harmonizing the stomach, regulating qi and relieving pain, and regulating the middle and diaphragm. It is a commonly used combination for treating liver and spleen together. The two are used for various symptoms of liver depression and qi stagnation, and stomach qi disharmony, such as pain in both ribs, stomach distension and pain, breast distension, chest fullness and stuffiness, etc.; fennel and clove warm the middle and dispel cold, descend the adverse and stop vomiting; patchouli can both eliminate dampness and harmonize the middle and stop vomiting, and treat vomiting caused by dampness and turbidity blocking the middle; Atractylodes lancea dries dampness and strengthens the spleen, and is combined with tangerine peel to warm and dry and remove dampness, promote qi and harmonize the stomach; ginger dispels wind and relieves exterior symptoms, and promotes lung and promotes water. The Chinese medicine composition of the present invention treats dampness and turbidity blocking the middle and spleen and stomach disharmony caused by distension and nausea and vomiting. Through modern pharmacological research, the antiemetic mechanism of traditional Chinese medicine ingredients has been gradually revealed, providing a new strategy for the prevention and treatment of CINV.

[0019] (2) Aromatherapy, as a complementary treatment method, has received research attention due to its potential efficacy. Experimental results show that the Chinese herbal compound essential oil (EOs) of the present invention shows potential efficacy in alleviating CINV. All doses of EOs provided in the experiment can reduce the pica behavior of rats, especially EOs-H, which can effectively improve the eating and drinking habits, and by down-regulating histamine and norepinephrine in serum, while up-regulating substances such as tryptophan, arginine, hydroxybutyric acid, tyrosine, phenylethylamine and alanine, it affects serum metabolites and metabolic pathways, and has a restorative effect on the abnormal metabolites caused by CINV. This provides an experimental basis for the use of Chinese herbal compound essential oil as a complementary treatment method for CINV. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The effect of Chinese herbal compound essential oil on kaolin intake in rats with chemotherapy-induced pica. Model represents the model group, Positive represents the positive control group, EO-L represents the low-dose group of Chinese herbal compound essential oil, EO-M represents the medium-dose group of Chinese herbal compound essential oil, and EO-H represents the high-dose group of Chinese herbal compound essential oil. Compared with the model group, * represents p<0.05; ** represents p<0.01.

[0021] Figure 2 The effect of Chinese herbal compound essential oil on the regular feed intake of chemotherapy-induced pica rats. Model represents the model group, Positive represents the positive control group, EO-L represents the low-dose group of Chinese herbal compound essential oil, EO-M represents the medium-dose group of Chinese herbal compound essential oil, and EO-H represents the high-dose group of Chinese herbal compound essential oil; compared with the model group, * represents p<0.05; ** represents p<0.01;

[0022] Figure 3The effect of Chinese herbal compound essential oil on the intake of glucose aqueous solution in rats with chemotherapy-induced pica. Model represents the model group, Positive represents the positive control group, EO-L represents the low-dose group of Chinese herbal compound essential oil, EO-M represents the medium-dose group of Chinese herbal compound essential oil, and EO-H represents the high-dose group of Chinese herbal compound essential oil. Compared with the model group, * represents p<0.05; ** represents p<0.01.

[0023] Figure 4 The effect of Chinese herbal compound essential oil on body weight of rats with chemotherapy-induced pica. Model represents the model group, Positive represents the positive control group, EO-L represents the low-dose group of Chinese herbal compound essential oil, EO-M represents the medium-dose group of Chinese herbal compound essential oil, and EO-H represents the high-dose group of Chinese herbal compound essential oil.

[0024] Figure 5 This is the OPLS-DA analysis of the rat pica nausea and vomiting model group and the normal control group. In the figure, Model represents the model group and Normal represents the normal control group.

[0025] Figure 6 Permutation model validation for OPLS-DA analysis of the model group and normal control group;

[0026] Figure 7 The volcano diagram of differential metabolites between the rat pica nausea and vomiting model group and the normal control group;

[0027] Figure 8 This is the sPLS-DA analysis of metabolites after the intervention of Chinese herbal compound essential oil on the chemotherapy-induced pica nausea and vomiting model in rats. In the figure, EOs-H represents the high-dose group of Chinese herbal compound essential oil, EOs-L represents the low-dose group of Chinese herbal compound essential oil, EOs-M represents the medium-dose group of Chinese herbal compound essential oil, Model represents the model group, Normal represents the normal control group, and Positive represents the positive control group;

[0028] Fig. 9 This is the metabolite heat map after the intervention of Chinese herbal compound essential oil on the chemotherapy-induced pica nausea and vomiting model in rats. In the figure, Model represents the model group, Normal represents the normal control group, EOs-L represents the low-dose group of Chinese herbal compound essential oil, EOs-M represents the medium-dose group of Chinese herbal compound essential oil, EOs-H represents the high-dose group of Chinese herbal compound essential oil, and Positive represents the positive control group;

[0029] Fig.10 Enrichment of metabolite-related metabolic pathways;

[0030] Fig.11 For correlation analysis among metabolites. DETAILED DESCRIPTION

[0031] The present invention provides a Chinese medicine composition for relieving the side effects of chemotherapy, wherein the Chinese medicine composition preferably comprises the following raw materials in parts by weight: 1-9 parts of dried tangerine peel, 1-9 parts of green tangerine peel, 1-9 parts of cloves, 1-9 parts of fennel, 1-9 parts of ginger, 1-9 parts of patchouli, and 1-9 parts of atractylodes; the Chinese medicine composition more preferably comprises the following raw materials in parts by weight: 2-7 parts of dried tangerine peel, 2-7 parts of green tangerine peel, 2-7 parts of cloves, 2-7 parts of fennel, 2-7 parts of ginger, 2-7 parts of patchouli, and 2-7 parts of atractylodes; the Chinese medicine composition further preferably comprises the following raw materials in parts by weight: 6 parts of dried tangerine peel, 6 parts of green tangerine peel, 6 parts of cloves, 6 parts of fennel, 6 parts of ginger, 6 parts of patchouli, and 6 parts of atractylodes. The Chinese medicine ingredients described in the present invention can all be purchased through conventional channels.

[0032] In the present invention, tangerine peel is the dried mature peel of the Rutaceae plant Citrus reticulata Blanco and its cultivars. It is bitter and pungent in taste and warm in nature. It enters the lung and spleen meridians. It has the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm. It is mainly used to treat abdominal distension, poor appetite, vomiting and diarrhea, and cough with excessive phlegm.

[0033] Qingpi is the dried young or immature fruit peel of Citrus reticulata Blanco and its cultivars. It tastes bitter and pungent, and is warm in nature. It enters the liver, gallbladder, and stomach meridians. It has the effects of soothing the liver and breaking up qi, and eliminating stagnation. It is mainly used to treat chest and flank pain, hernia pain, breast lumps, breast abscesses, food stagnation and qi stagnation, and abdominal pain.

[0034] Cloves are pungent and warm in nature. They enter the spleen, stomach, lung and kidney meridians. They have the effects of warming the middle and lowering adverse reactions, tonifying the kidney and supporting yang. They are mainly used to treat spleen and stomach deficiency and coldness, hiccups and vomiting, poor appetite, vomiting and diarrhea, cold pain in the heart and abdomen, and impotence due to kidney deficiency.

[0035] Fennel is spicy and warm in nature. It enters the liver, kidney, spleen and stomach meridians. It has the effects of dispelling cold and relieving pain, regulating qi and harmonizing the stomach. It is mainly used to treat abdominal pain caused by cold hernia, testicular prolapse, dysmenorrhea, cold pain in the lower abdomen, abdominal distension and pain, loss of appetite, vomiting and diarrhea.

[0036] Ginger is spicy and slightly warm in nature. It enters the lung, spleen and stomach meridians. It has the effects of dispelling cold, warming the middle and stopping vomiting, warming the lungs and stopping cough, and detoxifying. It is mainly used to treat colds, spleen and stomach coldness, stomach cold vomiting, and lung cold cough.

[0037] Patchouli is pungent and slightly warm in nature. It enters the spleen, stomach, and lung meridians. It has the effects of aromatic turbidity, harmonizing the middle and stopping vomiting, and relieving heat. It is mainly used to treat dampness and turbidity blocking the middle, abdominal distension and vomiting, summer dampness and superficial symptoms, the initial onset of damp-heat, fever and fatigue, chest tightness and discomfort, cold and dampness blocking the heat, abdominal pain, vomiting and diarrhea, and sinusitis and headache.

[0038] Atractylodes lancea, pungent, bitter, warm in nature; enters the spleen, stomach, and liver meridians. It has the effects of drying dampness and strengthening the spleen, dispelling wind and cold, and improving eyesight; it is mainly used to treat dampness blocking the middle jiao, abdominal distension, diarrhea, edema, beriberi, rheumatic arthralgia, colds, night blindness, and blurred vision.

[0039] The Chinese medicine composition of the present invention is compatible with various medicines, and mainly treats abdominal distension and pain and nausea and vomiting caused by dampness blocking the middle part of the body and disharmony between the spleen and stomach through the effects of promoting qi and removing dampness, strengthening the spleen and harmonizing the stomach.

[0040] The present invention also provides a traditional Chinese medicine compound essential oil for alleviating the side effects of chemotherapy. The traditional Chinese medicine compound essential oil comprises the traditional Chinese medicine composition.

[0041] The present invention also provides a preparation method of the traditional Chinese medicine compound essential oil, comprising the following steps: extracting tangerine peel, green peel, clove, fennel, ginger, patchouli and atractylodes lancea by steam distillation to obtain tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes lancea essential oil, respectively, and then mixing the traditional Chinese medicine essential oils obtained by the extraction to obtain the traditional Chinese medicine compound essential oil.

[0042] In the present invention, the extraction time of the steam distillation method is preferably 1 to 5 hours; more preferably 2 to 4 hours, and further preferably 3 hours.

[0043] In the present invention, the mass volume ratio of the traditional Chinese medicine to water during extraction by the steam distillation method is preferably 1:25-35; more preferably 1:28-32; further preferably 1:30.

[0044] In the present invention, the tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are mixed in a volume ratio of 1 to 10:1 to 10:1 to 10:1 to 10:1 to 10:1 to 10:1 to 10:1 to 10 to prepare a Chinese medicine compound essential oil. The tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are preferably mixed in a volume ratio of 1:1:1:1:1:1:1:1, more preferably in a volume ratio of 2 to 8:2 to 8:2 to 8:2 to 8:2 to 8:2 to 8:2 to 8:2 to 8 or in a volume ratio of 10:1:5:1:1:1:10 or in a volume ratio of 1:5:5:1:1:1:5.

[0045] In the present invention, the distillation temperature of the steam distillation method is preferably 95 to 100°C.

[0046] In the present invention, preferably tangerine peel, green peel, clove, fennel, ginger, patchouli and atractylodes are prepared to obtain crude essential oils through steam distillation, and then 1.5-2% by mass of sodium chloride is added to fully separate the oil-water mixture to prepare each Chinese medicine essential oil with higher purity.

[0047] In the present invention, taking tangerine peel as an example, the preparation method of tangerine peel essential oil is preferably as follows: pulverize tangerine peel, put it into a distillation device, add water, heat it at 95-100°C for extraction for 1-5h, make water vapor pass through the plant raw material, take out the aromatic components, cool the water vapor containing the aromatic components in a condenser to form a liquid; separate the essential oil and water through an oil-water separator to obtain a crude essential oil; add 1.5-2% sodium chloride to the crude essential oil, stir it fully, and filter it to obtain the tangerine peel essential oil.

[0048] The present invention also provides an application of the Chinese medicine composition or the Chinese medicine compound essential oil in preparing a medicine for alleviating and / or treating the side effects of chemotherapy.

[0049] In the present invention, the side effects include nausea and vomiting reactions occurring during chemotherapy and / or chemotherapy drug treatment.

[0050] In the present invention, the chemotherapy drugs include but are not limited to one or more of cisplatin, dacarbazine, nitrogen mustard and cyclophosphamide.

[0051] In the present invention, the Chinese herbal compound essential oil preferably enters the human body by inhalation, massage, etc., stimulates the hypothalamus, limbic system and prefrontal cortex, produces a physiological response that regulates the secretion of neurotransmitters (such as adrenocorticotropic hormone-releasing hormone, etc.), and thus achieves the purpose of alleviating and / or treating the side effects of chemotherapy.

[0052] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0053] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0054] Example 1

[0055] A Chinese medicine composition for alleviating the side effects of chemotherapy, wherein the composition comprises:

[0056] 6 parts of dried tangerine peel, 6 parts of green peel, 6 parts of cloves, 6 parts of fennel, 6 parts of ginger, 6 parts of patchouli, and 6 parts of atractylodes.

[0057] Example 2

[0058] A Chinese medicine composition for alleviating the side effects of chemotherapy, wherein the composition comprises:

[0059] 9 parts of dried tangerine peel, 6 parts of green peel, 8 parts of cloves, 6 parts of fennel, 9 parts of ginger, 6 parts of patchouli, and 9 parts of atractylodes.

[0060] Example 3

[0061] A Chinese medicine composition for alleviating the side effects of chemotherapy, wherein the composition comprises:

[0062] 6 parts of dried tangerine peel, 6 parts of green peel, 1 part of cloves, 6 parts of fennel, 1 part of ginger, 6 parts of patchouli, and 1 part of atractylodes.

[0063] Example 4

[0064] A Chinese medicine compound essential oil for alleviating side effects of chemotherapy, the Chinese medicine compound essential oil comprising the Chinese medicine composition of Example 1;

[0065] The preparation method of the above-mentioned traditional Chinese medicine compound essential oil is as follows: after extracting tangerine peel, green peel, clove, fennel, ginger, patchouli and atractylodes by steam distillation to obtain tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil, respectively, the tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are mixed in a volume ratio of 1:1:1:1:1:1:1 to obtain the traditional Chinese medicine compound essential oil;

[0066] Among them, the preparation method of tangerine peel essential oil is as follows: the tangerine peel is crushed and put into a distillation device, water is added according to the mass volume ratio of traditional Chinese medicine and water of 1:32, and it is extracted by high temperature heating at 100°C for 2 hours, so that water vapor passes through the plant raw material to take out the aromatic components, and the water vapor containing the aromatic components is cooled in a condenser to form a liquid; the essential oil and water are separated by an oil-water separator to obtain tangerine peel crude essential oil; 1.8% sodium chloride is added to the crude essential oil, fully stirred, and filtered to obtain tangerine peel essential oil.

[0067] The preparation methods of green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are the same as the preparation process of tangerine peel essential oil.

[0068] Example 5

[0069] A Chinese medicine compound essential oil for alleviating side effects of chemotherapy, the Chinese medicine compound essential oil comprising the Chinese medicine composition of Example 2;

[0070] The preparation method of the above-mentioned traditional Chinese medicine compound essential oil is as follows: after extracting tangerine peel, green peel, clove, fennel, ginger, patchouli and atractylodes by steam distillation to obtain tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil, respectively, the tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are mixed in a volume ratio of 1:1:1:1:1:1:1 to obtain the traditional Chinese medicine compound essential oil;

[0071] Among them, the preparation method of tangerine peel essential oil is as follows: the tangerine peel is crushed and put into a distillation device, water is added according to the mass volume ratio of traditional Chinese medicine and water of 1:35, and it is extracted by high temperature heating at 95°C for 5 hours, so that water vapor passes through the plant raw material to take out the aromatic components, and the water vapor containing the aromatic components is cooled in a condenser to form a liquid; the essential oil and water are separated by an oil-water separator to obtain tangerine peel crude essential oil; 2% sodium chloride is added to the crude essential oil, fully stirred, and filtered to obtain tangerine peel essential oil.

[0072] The preparation methods of green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are the same as the preparation process of tangerine peel essential oil.

[0073] Example 6

[0074] A Chinese medicine compound essential oil for alleviating side effects of chemotherapy, the Chinese medicine compound essential oil comprising the Chinese medicine composition of Example 3;

[0075] The preparation method of the above-mentioned traditional Chinese medicine compound essential oil is as follows: after extracting tangerine peel, green peel, clove, fennel, ginger, patchouli and atractylodes by steam distillation to obtain tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil, respectively, the tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are mixed in a volume ratio of 1:1:1:1:1:1:1 to obtain the traditional Chinese medicine compound essential oil;

[0076] The preparation method of tangerine peel essential oil is as follows: the tangerine peel is crushed and put into a distillation device, water is added according to the mass volume ratio of traditional Chinese medicine to water of 1:25, and the tangerine peel is extracted by high temperature heating at 100°C for 1 hour, so that water vapor passes through the plant raw material to take out the aromatic components, and the water vapor containing the aromatic components is cooled in a condenser to form a liquid; the essential oil and water are separated by an oil-water separator to obtain tangerine peel crude essential oil; 1.5% sodium chloride is added to the crude essential oil, fully stirred, and filtered to obtain tangerine peel essential oil.

[0077] The preparation methods of green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are the same as the preparation process of tangerine peel essential oil.

[0078] Example 7

[0079] This example explores the effect of the Chinese herbal compound essential oil obtained in Example 4 on the alleviation of CINV through olfaction and its intervention pathway on neurotransmitters

[0080] 1. Experimental Materials

[0081] (1) SPF Wistar male rats, weighing 200±20g, were randomly divided into 6 groups according to their body weight, with 12 rats in each group and housed in individual cages; the 6 groups were low-dose Chinese herbal compound essential oil group, medium-dose Chinese herbal compound essential oil group, high-dose Chinese herbal compound essential oil group, normal control group, model group, and positive control group.

[0082] (2) Preparation of kaolin particles

[0083] Weigh an appropriate amount of gum arabic powder at a ratio of 2%, take a corresponding amount of distilled water and slowly add it thereto, stir with a glass rod, then place it on an electromagnetic heating stirrer and stir at room temperature until it is completely dissolved; mix kaolin and 2% gum arabic solution to form lumps of moderate hardness and softness, and make particles similar in shape, size and hardness to rat feed, and dry them for later use.

[0084] 2. Experimental methods

[0085] Three days before modeling, kaolin particles were simultaneously administered to each group of animals (the kaolin particles were separated from the feed) to make the animals familiar with and adapt to the presence of kaolin. At the same time, 0.15% glucose aqueous solution was used instead of drinking purified water, and the animals were free to drink. The Chinese medicine compound essential oil prepared in Example 4 was mixed with grape seed base oil at a volume ratio of 4:6, 6:4 and 1:0 to prepare low, medium and high dose groups (EOs-L, EOs-M and EOs-H groups) for subsequent experiments. Starting from the 4th day, 200 μL of low, medium and high dose groups of absorbent cotton were placed 3 cm outside the rats, and sniffed for 45 minutes, once a day, for 3 consecutive days. The model group and the normal control group were given an equal volume (200 μL) of grape seed base oil for the same treatment. Starting from the 7th day, the positive control group (Positive) was intraperitoneally injected with granisetron hydrochloride aqueous solution, the normal control group and the model group were intraperitoneally injected with PBS, and the experimental groups (EOs-L, EOs-M and EOs-H) were the same as before. Starting at 9:00 a.m., 1 hour after the sniffing, rats in all groups except the blank group were intraperitoneally injected with cisplatin (6 mg / kg) to establish the model. On the 8th and 10th days, the feed was weighed and the samples (brainstem, stomach, ileum, whole blood) were collected. At 10:00 a.m. every day, the remaining kaolin in each rat cage was collected, and the normal feed and glucose water drinking bottle (containing glucose water solution) were weighed. The weights on the nth day and the n+1th day were subtracted to record the kaolin consumption, normal feed intake and glucose water consumption on the nth day.

[0086] Granisetron hydrochloride concentration is 0.27 mg / mL, dosage is 2.7 mg / kg / d. Cisplatin concentration is 1.2 mg / mL, dosage is 6 mg / kg, intraperitoneal injection (ip), injection volume is 1 mL / 100 g.

[0087] 3. Behavioral observation

[0088] Observe the general condition of the rats every day, including their spirit, fur, behavior, reaction sensitivity, breathing, and defecation. This includes whether the rats are restless, bite the cage, and then become listless, thin, have sparse fur, slow in movement, curl up, curl up, have loose stools, or die.

[0089] From the day of adding kaolin particles, the mass of kaolin was recorded once a day. Starting from one day before modeling, the test indicators of feed quality, glucose aqueous solution quality, and body weight were recorded until 72 hours after modeling.

[0090] 4. Animal handling and tissue specimen collection

[0091] (1) Collect stool samples

[0092] The animals in each group were killed in two batches 24h (acute vomiting) and 72h (delayed vomiting) after modeling. The rats were anesthetized with 60mg / kg pentobarbital, and a cardiac catheter was inserted from the left ventricle to the aorta. The right atrium was cut open and perfused with normal saline and 4% PFA successively. The brains were removed by decapitation and immediately fixed in 4% PFA.

[0093] The gastric antrum and ileum were removed, the contents were collected, and some were fixed in 4% PFA.

[0094] 5. Neurotransmitter detection

[0095] (1) Preparation of serum samples

[0096] Whole blood obtained from the vein was stored in a heparin anticoagulation tube, inverted, and centrifuged at 3000 rpm for 10 minutes. The supernatant was serum and stored at -80°C. The targeted metabolic technology platform (UPLC-TQMS) was used to quantitatively detect neurotransmitter metabolites in biological samples (Metabo-Profile, Shanghai, PRChina). This experiment was conducted under the guidance of the quality management system ISO9001:2015 (QAIC / CN / 170149). To reduce degradation, the sample was thawed in an ice bath. 10 μL of serum sample was drawn into a centrifuge tube, and 70 μL of methanol solution containing internal standard was added. The tube was shaken at 1400 rpm for 20 minutes at 10°C (MSC-100, Allsheng Instruments, Co., Ltd, Hangzhou, China). Centrifuged at 18000 for 20 minutes at 4°C (Microfuge20R, Beckman Coulter, Inc., IN, USA). 55 μL of supernatant was taken into a 96-well plate, vacuum dried (Centrivap Complete, Labconco, Kansas City, MO, USA), and then 50 μL of PITC derivatization solution was added. The plate was reacted at 30°C for 30 min, dried with nitrogen gas, and then 200 μL of 5 mM ammonium acetate methanol solution was added for re-dissolution. The plate was shaken for 30 min, centrifuged for 10 min, and 50 μL of supernatant was taken into a new 96-well plate. 50 μL of deionized water was added, mixed, and then waited for injection and analysis.

[0097] (2) Targeted metabolomics analysis

[0098] The samples were analyzed for neurotransmitters using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS / MS) (ACQUITY UPLC-XevoTQ-S, Waters Corp., Milford, MA, USA). The raw data files generated by UPLC-MS / MS were processed using MassLynx software (v4.1, Waters, Milford, MA, USA) to perform peak integration, calibration, and quantification for each metabolite. iMAP software (V1.0, Metabo-Profile, Shanghai, China) was used for subsequent statistical analyses, such as PCA, OPLS-DA, and unidimensional statistical tests.

[0099] 6. Experimental results

[0100] (1) Effects of Chinese herbal essential oil on the eating habits of chemotherapy-induced pica nausea and vomiting rats

[0101] To determine the antiemetic effect of EOs, we measured kaolin intake in rats from 0 to 72 hours after cisplatin injection. Figure 1 It can be seen that the consumption of kaolin in the model group (Model) rats increased significantly 24 hours after cisplatin injection (P<0.001), indicating that cisplatin injection successfully induced pica behavior. Compared with the model group, the intake of kaolin by rats in the positive control group (Positive) and the experimental group (EOs-L, EOs-M and EOs-H groups) decreased significantly, showing the relief effect of granisetron hydrochloride and EOs, among which high-dose traditional Chinese medicine compound essential oil (EOs-H) had the best relief effect on acute (24h) pica behavior. Figure 2 In the 48 hours after the injection of cisplatin, the normal feed intake of rats in each group did not differ significantly, but it decreased significantly at 72 hours (Positive and EOs-H), which may be related to the decreased appetite caused by pica behavior. Figure 3 As shown, 24 hours after injection of cisplatin, the demand for glucose solution in both the positive control group and the experimental group decreased, and the regulatory effect of the medium-dose group (EOs-M) lasted until 72 hours. Figure 4 No differences in body weight were observed among the groups.

[0102] In summary, different doses of EOs can alleviate cisplatin-induced pica behavior and reduce rats' intake of kaolin through sniffing treatment. The EOs-H group has a better effect on relieving acute nausea and vomiting, but it reduces the appetite of rats with pica. Continuous EOs treatment (48, 72h) has a better relief effect in the EOs-M group, reducing the demand for glucose solution and not having a significant effect on body weight. Studies have shown that aromatic components can regulate appetite through leptin resistance, sympathetic / parasympathetic nerve activity or mRNA expression of neuropeptide Y (NPY) / agouti-related protein (AgRP) and cocaine-amphetamine regulated transcript (CART) / proopiomelanocortin (POMC) in the hypothalamus.

[0103] (2) Effects of chemotherapy on serum metabolites in normal rats

[0104] The orthogonal partial least squares-discriminant analysis (OPLS-DA) model was established ( Figure 5 ) results show that the Model group is significantly different from the control group (Normal). However, supervised models may produce overfitting, so the model is usually subjected to a random permutation test (Permutation test) of 1000 random sample groupings, and the R2Y and Q2Y ( Figure 6), in order to prevent overfitting of the OPLS-DA model, the conditions were set as 1) OPLS-DA model R2Y>0.2; 2) the intercept of the Q2Y fitting curve on the Y axis <0, and the intercept of the Q2Y fitting curve on the Y axis <0. When the above conditions are met, the analysis results are used as the basis for screening differential metabolites. The substitution model shows that the model has a good explanation rate and prediction value.

[0105] The OPLS-DA model was used to obtain the variable importance of the projection (VIP) value of metabolites, and MetaboAnalyst 5.0 software was used to obtain the fold change (FC) and p value of metabolites according to the spectral intensity. Nine potential biomarkers ( Figure 7 ), which are the serum differential metabolites of the two groups. 72 hours after intraperitoneal injection of cisplatin, compared with the Model group, histamine, norepinephrine, and glutamine in the serum samples of the Normal group were significantly downregulated, while tryptophan, arginine, threonine, tyrosine, phenylethylamine, and alanine were upregulated. These neurotransmitters or neurotransmitter precursors are related to a variety of physiological or pathological conditions and are involved in regulating heart rate, blood pressure, stress, and the body's emotional response. Inhalation of essential oils or aromatic compounds can directly activate nasal olfactory chemoreceptors and olfactory signals, further triggering the production of neurotransmitters, affecting the neuroendocrine system and the sympathetic and parasympathetic nervous systems, leading to changes in psychology and eating habits.

[0106] (3) Effects of Chinese herbal essential oil on serum metabolites in the chemotherapy-induced pica nausea and vomiting model in rats

[0107] In order to study the difference of serum metabolites between the experimental group and the Positive group of chemotherapy-induced pica nausea and vomiting model rats treated with Chinese herbal compound essential oil, sparse partial least squares discriminant analysis (sPLS-DA) was used. The data matrix of EOs-L, EOs-M, EOs-H, Positive and Model groups was substituted into SIMCA-P14.1 software for multivariate statistical analysis ( Figure 8The results showed that the intervention of Chinese herbal compound essential oil had a significant clustering effect, while there was a significant separation between the experimental group and the model group, which indicated that Chinese herbal compound essential oil aromatherapy may have a significant effect on the metabolites of pica rats, leading to changes in metabolic characteristics. By comparing the data matrix of the ordinary control group and the experimental group, and performing cluster heat map analysis ( Fig. 9 ), it can be observed that the levels of some biomarkers in the experimental group and the positive control group have different degrees of correction, among which histamine and norepinephrine are significantly downregulated, while tryptophan, arginine, hydroxybutyric acid, tyrosine, phenylethylamine and alanine are upregulated to varying degrees, which is the same trend as the serum metabolites of the normal control group. This shows that the pica rats induced by cisplatin can play a certain degree of recovery role by regulating the secretion of neurotransmitters and other substances under the intervention of EOs, thus playing a positive role in the treatment of CINV.

[0108] (4) Metabolic pathway analysis

[0109] The metabolic pathways of 9 specific biomarkers with significant callback effects were analyzed ( Fig.10 ). The pathways of metabolite callback caused by aromatherapy with Chinese herbal compound essential oils may involve the urea cycle, aspartate metabolism, glycine and serine metabolism, phenylacetic acid metabolism, thyroid hormone synthesis, catecholamine biosynthesis, threonine and 2-ketobutyrate degradation, phenylalanine and tyrosine metabolism, ammonia recycling, amino sugar metabolism, niacin and nicotinamide metabolism, etc. These metabolic pathways not only provide neurotransmitter precursors, but also participate in their synthesis, decomposition and recycling processes. Any abnormality in the metabolic pathway may affect the level and function of neurotransmitters, thereby affecting the health and normal functioning of the nervous system. The correlation between metabolites is as follows: Fig.11 As shown in the figure, taurine, γ-aminobutyric acid (GABA), aspartic acid, alanine and glutamic acid play key roles in metabolism and neurotransmission, involving metabolic relationships, neurotransmitters (such as GABA), the formation of calcium ion channels, energy metabolism and neuroprotection, and are highly correlated with each other; in addition, tryptophan, phenylethylamine, tyrosine, threonine and arginine are involved in the synthesis of neurotransmitters such as serotonin, dopamine, norepinephrine and 5-hydroxytryptamine. The balance of these amino acids and their metabolites in the body is crucial to maintaining normal physiological functions. This further verifies that EOs can regulate metabolic pathways to maintain the stability of the body's physiological functions.

[0110] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for alleviating the side effects of chemotherapy, characterized in that: The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 1-9 parts of tangerine peel, 1-9 parts of green peel, 1-9 parts of cloves, 1-9 parts of fennel, 1-9 parts of ginger, 1-9 parts of patchouli, and 1-9 parts of atractylodes.

2. A Chinese herbal compound essential oil for alleviating the side effects of chemotherapy, characterized in that: The Chinese medicine compound essential oil comprises the Chinese medicine composition according to claim 1.

3. The method for preparing the Chinese medicinal compound essential oil according to claim 2, characterized in that: The method comprises the following steps: extracting tangerine peel, green peel, clove, fennel, ginger, patchouli and atractylodes lancea respectively by steam distillation to obtain tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes lancea essential oil, and then mixing the traditional Chinese medicine essential oils obtained by the extraction to obtain the traditional Chinese medicine compound essential oil.

4. The preparation method according to claim 3, characterized in that: The extraction time of the steam distillation method is 1 to 5 hours.

5. The preparation method according to claim 3, characterized in that: The mass volume ratio of the traditional Chinese medicine to water during extraction by the steam distillation method is 1:25-35.

6. The preparation method according to claim 3, characterized in that: The tangerine peel essential oil, green peel essential oil, clove essential oil, fennel essential oil, ginger essential oil, patchouli essential oil and atractylodes essential oil are mixed in a volume ratio of 1-10:1-10:1-10:1-10:1-10:1-10:1-10:1-10:1-10.

7. The preparation method according to claim 3, characterized in that: The distillation temperature of the steam distillation method is 95-100°C.

8. Use of the Chinese medicine composition according to claim 1 or the Chinese medicine compound essential oil according to claim 2 in the preparation of a drug for alleviating and / or treating the side effects of chemotherapy.

9. The use according to claim 8, characterized in that: The side effects include nausea and vomiting during chemotherapy and / or chemotherapy drug treatment.

10. The use according to claim 9, characterized in that: The chemotherapy drugs include one or more of cisplatin, dacarbazine, nitrogen mustard and cyclophosphamide.

Images