Application of epoxypatchoulene and its composition in preparing drugs for preventing and / or treating chemotherapy-related diarrhea

Abstract

The present invention relates to the use of epoxypatchoulene and a composition thereof in the preparation of a drug for preventing and / or treating chemotherapy-related diarrhea, and belongs to the field of biomedicine technology. On the one hand, the present invention synthesizes epoxypatchoulene for the first time and finds that epoxypatchoulene alone has the effect of alleviating weight loss and food intake loss and diarrhea, and can be used to prevent and / or treat chemotherapy-related diarrhea. On the other hand, the present invention finds that the combined use of epoxypatchoulene and loperamide, a drug for treating chemotherapy-related diarrhea, can synergistically enhance the effect of treating chemotherapy-related diarrhea, thereby improving the efficiency and scope of clinical drug use.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and specifically relates to the use of epoxypatchoulene and a composition thereof in the preparation of a drug for preventing and / or treating chemotherapy-related diarrhea. Background Art

[0002] Chemotherapy-induced diarrhea (CID) is the most common digestive complication in cancer patients during chemotherapy. It usually refers to painless or mildly painful diarrhea caused by cancer treatment, which is jet-like watery stool. The main clinical manifestations are nausea, vomiting, diarrhea, anorexia, malabsorption, etc. In severe cases, anorexia, water-electrolyte and acid-base imbalance, malnutrition, anemia, etc. may occur, and even chemotherapy-related death may occur. Among them, diarrhea is an important manifestation of chemotherapy side effects. With the promotion of chemotherapy drugs in the clinical treatment of tumors, while the efficacy is improved, the incidence of chemotherapy-related diarrhea is becoming increasingly common. Among them, 5-fluorouracil, irinotecan, methotrexate, cisplatin and other drugs are the most common. Chemotherapy-related diarrhea has the characteristics of high incidence and great harm. It often leads to symptoms such as ulcer formation, bleeding, diarrhea, and pain, which seriously affects the treatment and quality of life of cancer patients, increases the probability of infection and mortality, and also affects the progress of chemotherapy. Therefore, the prevention and treatment of chemotherapy-related diarrhea has extremely high clinical application value and social value in improving the quality of life and prognosis of cancer patients.

[0003] The main purpose of treating chemotherapy-related diarrhea is to control symptoms, relieve pain and prevent secondary infection. Among modern drugs, loperamide is the first choice for treating chemotherapy-related diarrhea. It has low bioavailability and directly acts on the opioid receptors of smooth muscle to block the release of acetylcholine and prostaglandins, thereby inhibiting intestinal motility and promoting the reabsorption of glucose and water and electrolytes to treat diarrhea. However, loperamide has limited efficacy in treating diarrhea with complications, and high doses may cause paralytic ileus. Octreotide is a synthetic octapeptide derivative of somatostatin that can directly act on epithelial cells, inhibit the secretion of gastrointestinal hormones and pancreas, inhibit gastrointestinal motility, prolong colon emptying time, regulate gastrointestinal electrolyte and water transport, reduce mesenteric blood flow and water and electrolyte secretion, and increase intestinal reabsorption of water and electrolytes. However, octreotide is expensive, and reports show that after prophylactic administration, it cannot prevent or reduce the occurrence or severity of diarrhea in patients with colorectal cancer compared with placebo, and may also cause fatty dysentery. To overcome the adverse reactions of these drugs, reducing the dosage is the most direct and effective way, but as the dosage is reduced, the efficacy and effective time also decrease. Therefore, screening safe and efficient drugs and their compositions for treating chemotherapy-related diarrhea is one of the important means to solve the problems of the existing technology. Summary of the invention

[0004] The purpose of the present invention is to overcome the problems existing in the above-mentioned prior art and to provide an application of epoxypatchoulene and a composition thereof in the preparation of a drug for preventing and / or treating chemotherapy-related diarrhea.

[0005] The present invention is achieved through the following technical solutions:

[0006] In a first aspect, the present invention provides the use of epoxypatchoulene in the preparation of a drug for preventing and / or treating chemotherapy-related diarrhea.

[0007] In a second aspect, the present invention provides use of a composition of epoxypatchoulene and loperamide in the preparation of a drug for preventing and / or treating chemotherapy-related diarrhea.

[0008] The present invention is the first to study and find that epoxypatchouliene has the effect of alleviating weight loss, food intake loss and diarrhea, and can be used to prevent and / or treat chemotherapy-related diarrhea. Loperamide is the first choice drug for treating chemotherapy-related diarrhea in modern medicine. The present invention has found through research that loperamide and epoxypatchouliene have a synergistic effect and can be used together in drugs for preventing and / or treating chemotherapy-related diarrhea.

[0009] The structural formula of the epoxypatchoulene is shown in formula (I):

[0010]

[0011] As a preferred embodiment of the application of the present invention, the chemotherapy-related diarrhea refers to diarrhea caused by tumor chemotherapy.

[0012] As a preferred embodiment of the application of the present invention, the chemotherapy-related diarrhea refers to intestinal pathological changes characterized by decreased body weight and food intake and diarrhea.

[0013] As a preferred embodiment of the application of the present invention, the drug further comprises a drug having no antagonistic effect on epoxypatchoulene and / or a pharmaceutically acceptable excipient.

[0014] When epoxypatchoulene is used together with a non-antagonistic drug or excipient such as loperamide, it also has the effect of alleviating weight loss, food intake loss and diarrhea, and can be used to prevent and / or treat chemotherapy-related diarrhea.

[0015] As a preferred embodiment of the application of the present invention, the dosage form of the drug includes oral preparations, injections, inhalants and external preparations.

[0016] As a preferred embodiment of the application of the present invention, the preparation method of epoxy patchouli is as follows: β-patchouliene and an oxidant react in an organic solvent at 0°C to 4°C to obtain the epoxy patchouli.

[0017] As a preferred embodiment of the application of the present invention, the oxidant is meta-chloroperbenzoic acid; the organic solvent is dichloromethane or chloroform; and the mass ratio of the β-patchoulene to the meta-chloroperbenzoic acid is 1:(1-2).

[0018] As a preferred embodiment of the use of the composition of epoxypatchouli and loperamide in the preparation of a drug for preventing and / or treating chemotherapy-related diarrhea, the mass ratio of the epoxypatchouli to the loperamide is (10-40):(10-40).

[0019] Preferably, the mass ratio of the epoxypatchoulene to the loperamide is 1:1.

[0020] Another object of the present invention is to provide a pharmaceutical composition for preventing and / or treating chemotherapy-related diarrhea, wherein the pharmaceutical composition comprises epoxypatchouli or a combination of epoxypatchouli and loperamide.

[0021] Epoxypatchoulene or a combination of epoxypatchoulene and loperamide is used in medicines, which have the effect of preventing and / or treating chemotherapy-related diarrhea, and expand the range of available drugs for treating chemotherapy-induced diarrhea.

[0022] The present invention has the following beneficial effects: The present invention discloses the use of epoxypatchoulene and a composition thereof in the preparation of a drug for preventing and / or treating chemotherapy-related diarrhea. On the one hand, the present invention first discovered that epoxypatchoulene has the effect of alleviating weight loss and food intake loss and diarrhea, and can be used to prevent and / or treat chemotherapy-related diarrhea. On the other hand, the combined use of epoxypatchoulene and loperamide, a drug for treating chemotherapy-related diarrhea, has a synergistically enhanced effect of treating chemotherapy-related diarrhea, and can improve the use efficiency and scope of drugs for treating chemotherapy-related diarrhea in the pharmaceutical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The chemical structure of epoxypatchoulene (PAO) was identified; Figure 1 A is the chemical structure identification of PAO: a is the chemical structure of PAO, b is the correlation between 1H-1H COSY and HMBC of PAO, and c is the NOESY correlation of PAO; Figure 1 B is the mass spectrum of PAO; Figure 1 C is the 1H-NMR spectrum of PAO; Figure 1 D is the 13C-NMR spectrum of PAO; Figure 1 E is the HMBC spectrum of PAO; Figure 1 F is the NOESY spectrum of PAO; Figure 1 G is the COSY spectrum of PAO;

[0024] Figure 2 The effect of PAO alone or in combination on 5-fluorouracil (5-FU)-induced chemotherapy-related diarrhea model cells; Figure 2 A is the effect of PAO alone on 5-FU-induced chemotherapy-related diarrhea model cells in Example 2; Figure 2 B is the effect of the combined use of PAO and loperamide (LP) in Example 3 on 5-FU-induced chemotherapy-related diarrhea model cells; Figure 2 C is the index diagram of PAO and LP combined medication; experimental data are indicates (n=6);

[0025] Figure 3 The effect of PAO alone on body weight, diet and diarrhea in rats with 5-FU-induced chemotherapy-related diarrhea in Example 4; wherein, Figure 3 A is the weight change of rats in each week; Figure 3 B is the diarrhea score of rats at each week; Figure 3 C is the change of rats’ diet in each week; experimental data is based on indicates (n=8);

[0026] Figure 4 The effect of PAO alone on the small intestinal tissue of rats with chemotherapy-related diarrhea induced by 5-FU in Example 4; wherein, Figure 4 A is a representative image of the small intestine pathological section stained with hematoxylin and eosin (H&E) (100×); Figure 4 B is the quantitative analysis histogram of H&E stained small intestine pathological sections; experimental data are indicates (n=6);

[0027] Figure 5 The effect of the combined use of PAO and LP on the body weight, diet and diarrhea of ​​rats with chemotherapy-related diarrhea induced by 5-FU in Example 5; wherein, Figure 5 A is the weight change of rats in each week; Figure 5 B is the diarrhea score of rats at each week; Figure 5 C is the change of diet amount of rats in each week; Figure 5 D is the index diagram of PAO and LP combined medication; experimental data are indicates (n=8);

[0028] Figure 6 The effect of the combined use of PAO and LP on the small intestinal tissue of rats with chemotherapy-related diarrhea induced by 5-FU in Example 5; wherein, Figure 6 A is a representative image of the small intestine pathological section stained with hematoxylin and eosin (H&E) (100×); Figure 6 B is the quantitative analysis histogram of H&E stained small intestine pathological sections; experimental data are Indicates (n=6). DETAILED DESCRIPTION

[0029] To better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments. It should be understood by those skilled in the art that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0030] Unless otherwise specified, the experimental methods used in the examples are all conventional methods; the materials, reagents, etc. used, unless otherwise specified, can be obtained from commercial channels.

[0031] In the example, the cell activity detection was performed using CCK8 reagent (Cat. No.: C0038), which was purchased from Shanghai Bio-Tech Biotechnology Co., Ltd. The specific operation steps were performed according to the reagent instructions.

[0032] Patchouli epoxyene (PAO) was sourced from the Drug Properties Research Laboratory of the School of Traditional Chinese Medicine of Guangzhou University of Chinese Medicine, with a purity greater than 95%. Loperamide hydrochloride capsules (LP, item number 181121506) were purchased from Xi'an Janssen Pharmaceuticals Co., Ltd.

[0033] The drug interactions in this experiment were determined by calculating the combination index (CI). The combination index (CI) was calculated and the results were exported using CompuSyn (Version 1.0) software. The effect and degree of drug interactions were evaluated according to the Chou-Talalay combination index method. The specific evaluation criteria are shown in Table 1.

[0034] Table 1 Evaluation criteria for drug interactions

[0035]

[0036] Example 1 Synthesis of Epoxy Patchoulene

[0037] 1. Experimental reagents and methods

[0038] A container containing 70 mL of dichloromethane was placed on an oscillator and oscillated at 4°C and 120 rpm. 5 g of β-patchoulene and 5.5 g of m-chloroperbenzoic acid were added to the container in sequence for reaction. The mass ratio of β-patchoulene to m-chloroperbenzoic acid was 1:1.1. After the reaction was complete, the mixture was filtered, and the filtrate was washed with a small amount of dichloromethane. The filtrate was washed with a saturated sodium bicarbonate solution to obtain an organic layer. The organic layer was concentrated to dryness by rotary evaporation to obtain epoxypatchoulene (PAO). The product was structurally analyzed by mass spectrometry, nuclear magnetic hydrogen spectrum, and two-dimensional nuclear magnetic spectrum HMBC, NOESY and COSY.

[0039] 2. Experimental results

[0040] The mass spectrometry results of the product ( Figure 1 B) shows that the molecular formula of the substance is C 15 H 24 O, m / z 220.1822.

[0041] Figure 1 The results of C NMR (CD3OD, 400MHz) showed: H 1.75(1H,m,H-2a),δ H 1.87(1H,m,H-2b),δ H 1.18(1H,m,H-3a),δ H 1.65(1H,m,H-3b),δ H 2.17(1H,overlapped,H-4),δ H 1.59(1H,d,J=14.8Hz,H-6a),δ H 2.17(1H,overlapped,H-6b),δ H 1.65(1H,m,H-7),δ H 1.32(1H,m,H-8a),δ H 1.81(1H,m,H-8b),δ H 1.40(1H,m,H-9a),δ H 1.98(1H,ddd,J=12.0,9.3,3.1Hz,H-9b),δ H 0.87(3H,s,H-12),δ H 0.95(3H,s,H-13),δ H 1.06(3H,s,H-14),δ H 1.03 (3H, d, J = 7.6 Hz, H-15).

[0042] Figure 1 The results of D-NMR carbon spectrum (CD3OD, 100MHz) showed: C 77.4(C-1),δ C 29.0(C-2),δ C 29.8(C-3),δ C 38.2(C-4),δ C 68.9(C-5),δ C 29.0(C-6),δ C 44.8(C-7),δ C 29.9(C-8),δ C 36.7(C-9),δ C 45.4(C-10),δ C45.9(C-11),δ C 24.4(C-12),δ C 19.0(C-13),δ C 16.7(C-14),δ C 17.6(C-15).

[0043] From the two-dimensional NMR spectrum HMBC ( Figure 1 E), NOESY( Figure 1 F) and COSY( Figure 1 G) Analysis confirmed that the unknown component was epoxypatchoulene (PAO).

[0044] Example 2 Effect of epoxypatchoulene on 5-fluorouracil-induced chemotherapy-related diarrhea model cells

[0045] 1. Experimental cells and methods:

[0046] The experimental cells were IEC-6 rat intestinal epithelial cell line (provided by ATCC American Type Culture Collection Center). When the number of IEC-6 cells increased exponentially, they were divided into 6 groups: normal group (Control), model group (Model), loperamide group (LP, 10μM, positive control), epoxypatchouli group (PAO, 10, 20 and 40μM). 4 The cells were seeded in a 96-well plate at a density of 10 cells / mL and adhered to the plate in a constant temperature incubator at 5% CO2 and 37°C for 24 hours. After serum starvation, in addition to the complete medium added to the normal group, the model group, loperamide group, and epoxypatchouli group were added with 70 μM 5-fluorouracil high-glucose medium without or with the corresponding drug, respectively, and cultured in the incubator for another 24 hours. The next day, the cells were collected for detection and analysis.

[0047] Observation indicators: Cell activity detection.

[0048] 2. Experimental results

[0049] After the administration, the above index levels were measured. The experimental data were The results are shown in Table 2 and Figure 2 As shown in A.

[0050] Table 2 IEC-6 cell activity detection

[0051]

[0052] Note: ## P<0.01, compared with the Control group; *P<0.05, **P<0.01, compared with the Model group

[0053] Table 2 and Figure 2 AThe results showed that both epoxypatchouli and loperamide could significantly enhance the activity of model cells, and the effect of epoxypatchouli was dose-dependent. The effect of epoxypatchouli in enhancing cell activity was comparable to that of loperamide. It can be seen that epoxypatchouli has the effect of resisting chemotherapy-related diarrhea.

[0054] Example 3 Effect of epoxypatchoulene combined with loperamide on 5-fluorouracil-induced chemotherapy-related diarrhea model cells

[0055] 1. Experimental cells and methods:

[0056] The experimental cells were IEC-6 rat intestinal epithelial cell line (provided by ATCC American Type Culture Collection Center). When the number of IEC-6 cells increased exponentially, they were divided into 11 groups: normal group (Control), model group (Model), loperamide group (LP, 10, 20 and 40μM), epoxypatchouli group (PAO, 10, 20 and 40μM), epoxypatchouli group and loperamide combination group (PAO+LP, 10, 20 and 40μM). According to 3.25×10 4 The cells were seeded at a density of 10 cells / mL in a 96-well plate and adhered to the wall in a constant temperature incubator at 5% CO2 and 37°C for 24 hours. After serum starvation, in addition to the addition of complete culture medium to the normal group, the model group, loperamide group, epoxypatchouli group and combination group were added with 70 μM 5-fluorouracil high-glucose culture medium without or with the corresponding drugs, and continued to be cultured in the incubator for 24 hours. The next day, the cells were collected for detection and analysis.

[0057] Observation indicators: Cell activity detection and calculation of drug combination index.

[0058] 2. Experimental results

[0059] After the administration, the above index levels were measured. The experimental data were The results are shown in Table 3, Table 4 and Figure 2 B. Figure 2 As shown in C.

[0060] Table 3 IEC-6 cell activity detection

[0061]

[0062] Note: ## P<0.01, compared with the Control group; *P<0.05, **P<0.01, compared with the Model group

[0063] Table 4 Effect of combined use of epoxypatchoulene (PAO) and loperamide (LP)

[0064]

[0065]

[0066] Table 3, Table 4 and Figure 2 B. Figure 2 The results showed that both epoxypatchouli and loperamide could significantly enhance the activity of model cells, and the intensity of the effects was dose-dependent. In addition, the combination of epoxypatchouli and loperamide also significantly enhanced the activity of model cells, and the intensity of the effects was also dose-dependent.

[0067] In the experiment of combining epoxypatchouli with loperamide to enhance the activity of model cells, by calculating the combination index (CI), it was found that epoxypatchouli and loperamide had a synergistic effect in enhancing the activity of model cells when used in combination at doses of 10, 20 and 40 μM.

[0068] The results of this example show that the combination of epoxypatchouliene and loperamide has a synergistic effect in preventing chemotherapy-related diarrhea. It can be seen that the combination of epoxypatchouliene and other drugs can be used as a drug for preventing chemotherapy-related diarrhea.

[0069] Example 4 Effect of epoxypatchoulene on 5-fluorouracil-induced chemotherapy-related diarrhea in rats

[0070] 1. Experimental animals and methods:

[0071] The experimental animals were male Sprague Dawley rats (provided by Guangdong Medical Animal Experimental Center), SPF grade, weighing 200±20g. After one week of adaptive feeding, they were randomly divided into 6 groups (8 rats in each group): normal group (Control), model group (5-FU), loperamide group (5-FU+LP, 10mg / kg), epoxypatchoulene group (5-FU+PAO, 10, 20 and 40mg / kg). From the 1st to the 4th day of the experiment, except for the normal group, which was given normal saline by intraperitoneal injection, the other groups were given 5-fluorouracil solution (35mg / kg) by intraperitoneal injection to establish a chemotherapy-related diarrhea model. The corresponding drugs were given for treatment at the same time as the modeling, and the volume of oral administration was 1mL / 100g, which was continued for 7 days. On the last day of the experiment, the rats were euthanized and the small intestinal tissues were collected. Pathological sections were prepared from the small intestinal tissue and stained with hematoxylin-eosin (H&E). The results of the section staining were evaluated in a blinded manner. The crypts, villi, epithelium, and inflammatory infiltration of the small intestine were analyzed according to the score range of 0 (no damage) to 3 (severe damage). During the experiment, the diet and body weight of the rats were recorded. The diarrhea of ​​each rat was observed and scored according to the Bowen index system, with the following criteria: normal was 0 points, mild diarrhea (slightly wet, soft feces) was 1 point, moderate diarrhea (wet, unformed feces) was 2 points, and severe diarrhea (watery feces, severe perianal staining) was 3 points.

[0072] Observation indicators: body weight, diarrhea score, food intake, and histopathological score.

[0073] 2. Experimental results

[0074] After the administration, the above index levels were measured. The experimental data were The results are shown in Table 5, Table 6 and Figure 3 , Figure 4 shown.

[0075] Table 5 Body weight, diarrhea scores and food intake of rats in each group during the experiment

[0076]

[0077]

[0078] Note: ## P<0.01, compared with the Control group; *P<0.05, **P<0.01, compared with the 5-FU group

[0079] Table 6 Histopathological scores of small intestine of rats in each group

[0080]

[0081] Note:## P<0.01, compared with the Control group; *P<0.05, **P<0.01, compared with the Model group

[0082] The experimental results showed that both epoxypatchouli and loperamide could improve the weight loss, food intake and diarrhea of ​​the model rats, and the effect of epoxypatchouli was dose-dependent. Epoxypatchouli and loperamide alleviated the pathological changes of the small intestine tissue of the model rats, which was consistent with their pathological scores. It can be seen that epoxypatchouli has the effect of resisting chemotherapy-related diarrhea.

[0083] Example 5 Effect of epoxypatchoulene combined with loperamide on 5-fluorouracil-induced chemotherapy-related diarrhea in rats

[0084] 1. Experimental animals and methods:

[0085] The experimental animals were male Sprague Dawley rats (provided by Guangdong Medical Animal Experimental Center), SPF grade, weighing 200±20g. After one week of adaptive feeding, they were randomly divided into 11 groups (8 rats in each group): normal group (Control), model group (5-FU), loperamide group (5-FU+LP, 10, 20 and 40 mg / kg), epoxypatchouli group (5-FU+PAO, 10, 20 and 40 mg / kg), epoxypatchouli combined with loperamide group (5-FU+PAO+LP, 10, 20 and 40 mg / kg). From the 1st to the 4th day of the experiment, except for the normal group, which was given normal saline by intraperitoneal injection, the other groups were given 5-fluorouracil solution (35 mg / kg) by intraperitoneal injection to establish the chemotherapy-related diarrhea model. The corresponding drugs were given for treatment at the same time of modeling, and the volume of oral administration was 1mL / 100g, and the administration was continued for 7 days. On the last day of the experiment, the rats were euthanized and the small intestinal tissues were collected. Pathological sections of the small intestinal tissues were made and stained with hematoxylin-eosin (H&E). The results of the section staining were evaluated blindly, and the crypts, villi, epithelium, and inflammatory infiltration of the small intestine were analyzed according to the score range of 0 (no damage) to 3 (severe damage). During the experiment, the diet and body weight of the rats were recorded. At the same time, the diarrhea of ​​each rat was observed and scored according to the Bowen index system, with the following standards: normal was 0 points, mild diarrhea (slightly wet, soft feces) was 1 point, moderate diarrhea (wet, unformed feces) was 2 points, and severe diarrhea (watery feces, severe perianal staining) was 3 points.

[0086] Observation indicators: body weight, diarrhea score, food intake, histopathological score, and calculation of drug combination index.

[0087] 2. Experimental results

[0088] After the administration, the above index levels were measured. The experimental data were The results are shown in Table 7, Table 8, Table 9 and Figure 5 , Figure 6 shown.

[0089] Table 7 Body weight, diarrhea scores and food intake of rats in each group during the experiment

[0090]

[0091]

[0092]

[0093]

[0094]

[0095] Note: ## P<0.01, compared with the Control group; *P<0.05, **P<0.01, compared with the 5-FU group

[0096] Table 8 Histopathological scores of small intestine of rats in each group

[0097]

[0098] Note: ## P<0.01, compared with the Control group; *P<0.05, **P<0.01, compared with the Model group

[0099] Table 9 Effect of combined use of epoxypatchoulene (PAO) and loperamide (LP)

[0100]

[0101] The experimental results show that both epoxypatchouli and loperamide can improve the weight loss, diet loss and diarrhea of ​​model rats, and the effect intensity of epoxypatchouli is dose-dependent. In addition, the combination of epoxypatchouli and loperamide also has the effect of improving the weight loss, diet loss and diarrhea of ​​model rats, and its effect intensity is also dose-dependent. In the experiment of epoxypatchouli combined with loperamide to improve the weight loss, diet loss and diarrhea of ​​model rats, by calculating the combination index (CI), it was found that epoxypatchouli and loperamide had a synergistic effect in improving the weight loss, diet loss and diarrhea of ​​model rats at a dose of 10, 20 and 40 mg / kg.

[0102] The results showed that the combination of epoxypatchoulene and loperamide had a synergistic effect in preventing chemotherapy-related diarrhea. It can be seen that the combination of epoxypatchoulene and other drugs can be used as a drug for preventing chemotherapy-related diarrhea.

[0103] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. Use of a composition of epoxypatchoulene and loperamide in the preparation of a drug for preventing and / or treating chemotherapy-related diarrhea, characterized in that: The mass ratio of the epoxypatchoulene to the loperamide is (10-40):(10-40).

2. The use according to claim 1, characterized in that: The chemotherapy-related diarrhea refers to diarrhea caused by tumor chemotherapy.

3. The use according to claim 1, characterized in that: The chemotherapy-related diarrhea refers to intestinal pathological changes characterized by decreased body weight and food intake and diarrhea.

4. The use according to claim 1, characterized in that: The drug also includes drugs and / or pharmaceutically acceptable excipients that have no antagonistic effect on epoxypatchoulene.

5. The use according to claim 1, characterized in that: The dosage forms of the drug include oral preparations, injections, inhalants and external preparations.

6. The use according to claim 1, characterized in that: The preparation method of epoxy patchouliene is as follows: under the condition of 0°C to 4°C, beta-patchouliene and an oxidant are reacted in an organic solvent to obtain the epoxy patchouliene.

7. The use according to claim 6, characterized in that: The oxidant is meta-chloroperbenzoic acid; the organic solvent is dichloromethane or chloroform; the mass ratio of the β-patchoulene to the meta-chloroperbenzoic acid is 1:(1-2).

8. A pharmaceutical composition for preventing and / or treating chemotherapy-related diarrhea, characterized in that: The pharmaceutical composition comprises a combination of epoxypatchoulene and loperamide.

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