Pharmaceutical composition for improving oral bioavailability of arecoline

Abstract

The invention belongs to the technical field of medicines, and discloses a composition for improving bioavailability of arecoline. Specifically, the composition specifically comprises arecoline and magnolol, and the weight ratio of arecoline to magnolol in the pharmaceutical composition is (1: 0.1)-(1: 15). According to the composition, the in-vivo bioavailability of the arecoline can be remarkably improved, the half-life period and the average residence time of the arecoline can be prolonged, the application range of the arecoline is widened, and the treatment effect of the arecoline on diseases such as tapeworm infection, abdominal distension, diarrhea, edema, cancer, Alzheimer's disease, cerebral apoplexy, epilepsy and viral pneumonia can be better exerted.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a pharmaceutical composition containing arecoline, which improves the oral bioavailability and duration of arecoline in vivo, and its application in drugs for treating diseases such as tapeworm infection, abdominal distension, diarrhea, edema, cancer, Alzheimer's disease, stroke, epilepsy, and viral pneumonia. It belongs to the field of pharmaceutical technology. Background Technology

[0002] Areca catechu is the fourth most common drug in the world after tobacco, alcohol, and caffeine. [1] It can be used to treat diseases such as tapeworm infection, abdominal distension, diarrhea, and edema. Arecoline (1,2,5,6-tetrahydro-1-methylnicotinic acid ester) is the main active ingredient in areca nut, with a content between 0.1% and 0.5%. Arecoline can act on M-cholinergic receptors. [2] It promotes bodily excitation and enhances learning and memory abilities. [3] Its main metabolite, arecoline, can inhibit the uptake of the central inhibitory neurotransmitter gamma-aminobutyric acid (GABA). [4] This can improve cognitive function and memory in Alzheimer's patients. [5] Studies by Dasgupta et al. have found that arecoline can enhance the body's immunity by regulating the activity of adrenaline in the body. [6,7] In addition, arecoline also has unique pharmacological effects such as vasodilation, antithrombosis, inhibition of lipid differentiation, antibacterial, anti-inflammatory, and antitumor properties. [8-10] Arecoline is a small-molecule quaternary ammonium compound that is rapidly absorbed, has low oral bioavailability, and a short residence time in the body. [11,12] This has severely hampered its application. Further research has revealed that, in addition to its high molecular polarity, the widespread presence of carboxylesterases in the body is a major reason for the low oral bioavailability of arecoline. Therefore, enhancing the in vivo bioavailability of arecoline and prolonging its elimination half-life are crucial steps to overcome this technological bottleneck.

[0003] In Chinese patent CN114451575A

[13] Shenzhen Jierxun Technology Co., Ltd. has developed a composition containing arecoline, propylene glycol, glycerol, and mixed additives, which significantly improves the physiological efficacy of arecoline; this is documented in Chinese Patent CN106561660A.

[14] In China, Xuzhou Dezhu Biotechnology Co., Ltd. combined iris flavin and arecoline, significantly improving the bactericidal and insecticidal effects of arecoline; this is documented in Chinese patent CN113812665A.

[15] Yunnan Bagu Biotechnology Co., Ltd. has combined arecoline citrate salt, propylene glycol, glycerol, and characteristic flavor enhancers to significantly improve the application efficiency of arecoline; this is documented in Chinese patent CN105123700A.

[16] Tang Rui et al. combined thymol and arecoline and found that they had a synergistic effect; this was demonstrated in Chinese patents CN101428027B and CN101411705B. [17,18] Beijing Cedvicon Pharmaceutical Research Institute combines effective amounts of arecoline, tetramethylpyrazine, and paeonol to prevent thrombosis and atherosclerosis. This is described in Chinese patent CN107982264A.

[19] The Wuhan Academy of Agricultural Sciences used a combination of praziquantel, arecoline, cucurbitacin, osthol, and excipients to treat echinococcosis in animals. The drugs worked synergistically, resulting in significant therapeutic effects.

[0004] Magnolol is the main component of Magnolia officinalis and has antibacterial, antiviral, antioxidant, antidepressant and central nervous system depressant effects

[20] . It has been reported that magnolol can reduce alveolar damage in lung tissue and inhibit the inflammatory response of viral pneumonia caused by influenza A virus (H1N1).

[21] Liang Zhensheng discovered that magnolol can affect cell wall permeability, thereby exerting a broad-spectrum and highly effective effect against respiratory pathogens.

[22] Carboxylesterase (EC3.1.1.1, CES) is a class of enzymes that play a crucial role in drug metabolism, detoxification, and lipid mobilization.

[23] These are members of the serine hydrolase superfamily, which exhibit broad specificity for substrates containing functional groups such as carboxyl esters, thioesters, or amides.

[24] This includes different molecular groups, including drugs (clopidogrel, methylphenidate, oseltamivir, temopril, irinotecan, and procaine, etc.), pesticides (malathion and permethrin), and lipids (2-arachidonicylglycerol (2-AG) and arachidonic acid ethanolamine (AEA), causing significant changes in drug structure, lipophilicity, or both. Therefore, CES plays an important role in the in vivo biotransformation of ester or amide prodrugs.

[25] Magnolol is a potent inhibitor of CES.

[26] Magnolol may affect the absorption of drugs containing functional groups of carboxyl esters, thioesters or amides.

[0005] The aforementioned patents involve compositions that enhance the efficacy of arecoline, but they differ fundamentally from the arecoline composition described in this patent. Arecoline can be used to treat diseases such as tapeworm infection, abdominal distension, diarrhea, edema, and viral pneumonia, but its low bioavailability limits its application. In view of this, the present invention improves the in vivo bioavailability of arecoline by selecting magnolol, which has carboxylesterase inhibitory activity, to form a composition with arecoline. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a pharmaceutical composition containing arecoline to improve the oral bioavailability of arecoline and prolong its in vivo half-life.

[0007] The pharmaceutical composition of the present invention contains the active ingredients arecoline and magnolol.

[0008] The present invention achieves its objective through the following technical solutions:

[0009] One objective of this invention is to provide a pharmaceutical composition containing arecoline, wherein the pharmaceutical composition includes tablets, emulsions, capsules, pills, oral liquid preparations, granules, powders, ointments, microspheres, microcapsules, sustained-release preparations, or controlled-release preparations.

[0010] The second objective of this invention is to provide the effect of a pharmaceutical composition containing arecoline on the oral absorption of arecoline.

[0011] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0012] 1. Characteristics of pharmaceutical compositions containing arecoline:

[0013] 1.1 The pharmaceutical composition containing arecoline designed in this invention comprises the active ingredients arecoline and magnolol, wherein the weight ratio of arecoline to magnolol in the pharmaceutical composition is 15:1 to 1:10.

[0014] 1.2 Preferably, the pharmaceutical composition is arecoline prepared alone and then used in combination with magnolol, or mixed with magnolol and then used as a composition.

[0015] 1.3 Preferably, the arecoline is a pharmacologically acceptable salt.

[0016] 1.4 Preferably, the pharmacologically acceptable salt of arecoline is its hydrochloride, nicotinate, citrate, bisulfate, maleate, hydrobromide, hydroiodide, nitrate, or oxalate.

[0017] 1.5 Preferably, the magnolol is one or more of a monomer, salt, or eutectic.

[0018] 2. Dosage and characteristics of pharmaceutical compositions containing arecoline:

[0019] 2.1 The pharmaceutical composition of the present invention comprises an effective dose of arecoline and a pharmaceutically acceptable carrier.

[0020] 2.2 The pharmaceutical composition of the present invention has a daily dosage of arecoline in the range of 5 mg to 1000 mg.

[0021] 2.3 The pharmaceutical composition involved in this invention is in the dosage form of tablets, emulsions, capsules, pills, oral liquid preparations, granules, powders, ointments, microspheres, microcapsules, sustained-release preparations, or controlled-release preparations.

[0022] 2.4 The use of the arecoline pharmaceutical composition of the present invention in the preparation of various drugs for the prevention and / or treatment of diseases and complications such as tapeworm infection, abdominal distension, diarrhea, edema, cancer, Alzheimer's disease, stroke, epilepsy and viral pneumonia.

[0023] This invention relates to pharmaceutical compositions using arecoline as the active ingredient. These pharmaceutical compositions can be prepared according to methods known in the art. Any dosage form suitable for human or animal use can be formulated by combining the arecoline pharmaceutical composition of this invention with one or more pharmaceutically acceptable solid or liquid excipients and / or adjuvants. The arecoline pharmaceutical composition of this invention typically comprises 10-90% by weight.

[0024] The arecoline pharmaceutical composition of the present invention can be administered in unit dose form, and the route of administration can be enteric or non-enteric, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosa, eye, lung and respiratory tract, skin, vagina, rectum, etc.

[0025] The preferred dosage form for administration in this invention is a solid dosage form. Solid dosage forms can be tablets (including regular tablets, enteric-coated tablets, lozenges, dispersible tablets, chewable tablets, effervescent tablets, orally disintegrating tablets), capsules (including hard capsules, soft capsules, and enteric-coated capsules), granules, powders, microcapsules, droplets, suppositories, films, patches, aerosols, sprays, etc.

[0026] The arecoline pharmaceutical composition of the present invention, and the mixed solid substance of the arecoline pharmaceutical composition of the present invention, can be made into ordinary preparations, sustained-release preparations, controlled-release preparations, targeted preparations, and various microparticle delivery systems.

[0027] To formulate the arecoline pharmaceutical composition of the present invention into tablets, a wide variety of excipients known in the art can be used, including diluents, binders, wetting agents, disintegrants, lubricants, and flow aids. Diluents can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, dicalcium phosphate, calcium carbonate, etc.; wetting agents can be water, ethanol, isopropanol, etc.; binders can be starch paste, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, gum arabic paste, gelatin paste, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol, etc.; disintegrants can be dry starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxyethylene sorbitol fatty acid ester, sodium dodecyl sulfonate, etc.; lubricants and flow aids can be talc, silica, stearate, tartaric acid, liquid paraffin, polyethylene glycol, etc.

[0028] Tablets can also be further processed into coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or bilayer and multilayer tablets.

[0029] To formulate the drug delivery unit into capsules, the active ingredient, mesalazine-arginine co-amorphous compound of the present invention, can be mixed with a diluent and a flow aid, and the mixture can be directly placed into hard or soft capsules. Alternatively, the pharmaceutical composition of the active ingredient, arecoline of the present invention, can be first formed into granules or microspheres with a diluent, binder, and disintegrant, and then placed into hard or soft capsules. Various diluents, binders, wetting agents, disintegrants, and flow aids used to prepare tablets of the arecoline pharmaceutical composition of the present invention can also be used to prepare capsules of the arecoline pharmaceutical composition of the present invention.

[0030] In addition, colorants, preservatives, flavorings, tasters or other additives may be added to pharmaceutical preparations if necessary.

[0031] To achieve the purpose of medication and enhance the therapeutic effect, the drug or drug composition of the present invention can be administered using any known method of administration.

[0032] The dosage of the arecoline pharmaceutical composition of the present invention can vary widely depending on the nature and severity of the disease to be prevented or treated, the individual condition of the patient or animal, the route of administration, and the dosage form. The above dosage can be administered as a single unit or divided into several units, depending on the physician's clinical experience and the administration regimen, including the use of other treatment methods.

[0033] The arecoline pharmaceutical composition of this invention can be taken alone or in combination with other therapeutic or symptomatic drugs. When the arecoline pharmaceutical composition of this invention has a synergistic effect with other therapeutic drugs, its dosage should be adjusted according to the actual situation.

[0034] The technical solution of the present invention also includes the application of the above-described pharmaceutical composition in the preparation of remedies for tapeworm infection, abdominal distension, diarrhea, edema, cancer, Alzheimer's disease, stroke, epilepsy, and viral pneumonia. 3. Beneficial technical effects of the present invention:

[0035] The pharmaceutical composition of this invention has a significant absorption-enhancing effect, can effectively exert a synergistic effect, and its efficacy is not affected by conventional formulation processes. It can effectively improve the oral bioavailability of arecoline, prolong its elimination half-life and residence time in the body, and effectively solve the long-standing problems of low oral bioavailability and rapid elimination of arecoline. Figure 1 , 2 ) Attached Figure Description

[0036] Figure 1 Arecoline (300 mg / kg) group and arecoline (300 mg / kg) + magnolol (100 mg / kg) group: plasma concentration-time curves in SD rats after oral administration.

[0037] Figure 2 Arecoline absorption rate in SD rats in combination with different proportions Detailed Implementation

[0038] To better illustrate the technical solution of the present invention, the following embodiments are provided, but the present invention is not limited thereto.

[0039] Example 1

[0040] Preparation method 1 of combination drug formulation (tablets):

[0041] A method for preparing a combination drug tablet, characterized by using a arecoline drug composition and several excipients as excipients for preparing the combination drug tablet, and preparing tablet samples with each tablet containing 5-1000 mg of eutectic crystals according to a certain ratio. Table 1 shows the tablet formulation ratio:

[0042] Table 1. Formulations for preparing arecoline-containing pharmaceutical tablets

[0043]

[0044] The method for preparing tablet formulations using arecoline drug compositions as raw materials is as follows: several excipients are mixed evenly with the raw material and directly compressed into tablets; or the excipients are mixed and granulated by dry method, then mixed evenly with the raw material and compressed into tablets.

[0045] Preparation method 2 for combination drug formulations (tablets):

[0046] A method for preparing a combination drug tablet, characterized by using a arecoline drug composition and several excipients as excipients for preparing the combination drug tablet, and preparing tablet samples with each tablet containing 5-1000 mg of eutectic crystals according to a certain ratio. Table 2 gives the tablet formulation ratio:

[0047] Table 2. Formulations for preparing arecoline-containing pharmaceutical tablets

[0048]

[0049] The method for preparing tablet formulations using arecoline drug composition as raw material is as follows: several excipients are mixed evenly with the raw material, an appropriate amount of 1% sodium hydroxymethyl cellulose solution is added to make a soft material, which is then granulated by sieving, the wet granules are dried, sieved and sized, magnesium stearate and talc are added and mixed evenly, and then compressed into tablets to obtain the final product.

[0050] Preparation method 3 of combination drug formulation (capsule):

[0051] A method for preparing a combination drug capsule, characterized by using a arecoline drug composition as the raw material and several excipients as excipients for preparing the combination drug capsule, and preparing capsule samples with a drug content of 5-1000mg per tablet according to a certain ratio. Table 3 shows the capsule formulation ratio:

[0052] Table 3. Formulations of active pharmaceutical ingredients and excipients for arecoline-containing drug capsules.

[0053]

[0054] The method for preparing capsules using arecoline drug compositions as raw materials is as follows: several excipients are mixed evenly with the raw materials, an appropriate amount of 1% sodium hydroxymethyl cellulose solution is added, wet granules are prepared, dried, sieved and granulated, magnesium stearate is added and mixed evenly, and then inserted into capsules; or, without using the granulation step, berberine hydrochloride and malic acid raw materials are directly mixed evenly with several excipients and excipients, sieved, and then directly filled into capsules.

[0055] Example 2

[0056] Dosage of arecoline composition drug 1 (tablet):

[0057] A pharmaceutical composition developed using arecoline as the active pharmaceutical ingredient is characterized in that the arecoline pharmaceutical composition, as the active pharmaceutical ingredient, is administered at a daily dose of 900 mg, and can be prepared as 3 ordinary tablets of 100 mg three times a day, or 1 tablet of 300 mg three times a day.

[0058] Dosage of arecoline composition drug 2 (capsule):

[0059] A pharmaceutical composition developed using a pharmaceutical composition containing arecoline as the active pharmaceutical ingredient is characterized by using a pharmaceutical composition containing arecoline as the active pharmaceutical ingredient, with a daily dosage of 1200 mg, which can be prepared as 4 capsules of 100 mg three times a day or 4 capsules of 150 mg twice a day.

[0060] Issues to be clarified: The dosage of the arecoline composition involved in this invention is influenced by many factors, such as patient age, body surface area, route of administration, frequency of administration, and treatment purpose, all of which result in different dosages per administration. Differences in absorption and blood drug concentration between samples also contribute to the fact that the appropriate dosage range for each use of the arecoline composition is 0.5-50 mg / kg body weight, preferably 5-30 mg / kg body weight. Different total dosage regimens of the arecoline composition should be developed based on the specific treatment needs, and can be administered in multiple or single doses.

[0061] Example 3

[0062] Formulation: The formulation of the drug combination of magnolol and arecoline is shown in Table 4.

[0063] Table 4. Formulation of arecoline and magnolol

[0064]

[0065]

[0066] Preparation method: After mixing the pharmaceutical composition containing arecoline, add 10 mL of 0.5% sodium carboxymethyl cellulose and mix thoroughly to obtain the pharmaceutical composition.

[0067] Example 4

[0068] Pharmacokinetics of magnolol-arecoline oral absorption

[0069] (1) Instruments

[0070] Chromatograph: Agilent 1200 high performance liquid chromatograph, Agilent Technologies;

[0071] Mass spectrometer: Agilent 6110 single quadrupole mass spectrometer, Agilent Technologies;

[0072] Data processing was performed using the software Drug Analysis System 2.0, manufactured by MaS Studio Co., Ltd. in China.

[0073] Centrifuge: Allegra™ X-22R Centrifuge, Beckman Coulter, USA;

[0074] Analytical balance: XS105 analytical balance, Mettler AG, Switzerland.

[0075] (2) Analysis conditions

[0076] The Welch SCX column had a particle size, inner diameter, and column length of 5 μm, 4.6 mm, and 250 mm, respectively. The mobile phase used was [missing information - likely a specific component or parameter]. The column temperature was 30 °C. The mobile phase consisted of an aqueous solution containing 0.2% formic acid, adjusted to pH 3.8 with ammonia, and acetonitrile (45:55, v / v). The ESI source was in positive ion monitoring mode, with a drying gas flow rate of 10.0 L / min, a drying gas temperature of 350 °C, a nebulizer pressure of 35.0 psig, and a capillary voltage of 3000 V. The mass spectrometer detector was in selective ion monitoring mode (SIM). The mass-to-charge ratios (m / z) of arecoline and sophoridine were 156 and 247, respectively.

[0077] (3) Sample preparation

[0078] Internal standard solution: Accurately weigh sophoridine reference standard and dilute to volume with 50% methanol-water to prepare sophoridine solution with a concentration of 1000 ng / mL;

[0079] Take 100 μL of plasma and add 10 μL of 120 mg / mL vitamin C solution, 10 μL of 5% formic acid solution and 10 μL of internal standard; shake for 3 min, add 400 μL of pre-cooled methanol; shake for 3 min, centrifuge at 13400 rpm for 15 min; take the supernatant and blow it dry with nitrogen, add 100 μL of 50% methanol-water to reconstitute, shake well and load the sample; the injection volume is 20 μL.

[0080] (4) Experimental methods

[0081] In this example, six male SPF-grade SD rats, weighing 260g, were randomly divided into two groups of three. The two groups were administered arecoline (300mg / kg) and arecoline (300mg / kg) combined with magnolol (100mg / kg) by gavage, respectively. At 0, 5, 10, 15, 30, 45, 60, 90, 120, 240, 360, 480, and 720 min after administration, approximately 0.2mL of blood was collected from the posterior venous plexus of the rats' eyes and placed in 1.5mL centrifuge tubes pretreated with EDTA. The tubes were then centrifuged at 5000r / min for 15 min at 4°C, and the supernatant was used to determine the plasma drug concentration.

[0082] (5) Experimental Results

[0083] The corresponding magnolol-arecoline plasma concentration curve based on the pharmacokinetic results is shown below. Figure 1 The pharmacokinetic parameters of the arecoline group (300 mg / kg) and the arecoline (300 mg / kg) combined with magnolol (100 mg / kg) group are shown in Table 5.

[0084] When arecoline is administered at a dose of 300 mg / kg, the C of arecoline at 0.1 mmol / L for 67 hours is... max The concentration was 327.0 ng / mL, the elimination half-life in vivo was 0.3 h, and the in vivo exposure was 54.2 mg / L·h. When combined with 50 mg / kg magnolol, the C15 of arecoline was 1.5 h. max The concentration was 1486.1 ng / mL, the elimination half-life was 0.62 h, and the in vivo exposure was 1182.5 mg / L·h. This means that when arecoline was administered in combination with magnolol at a dose of 50 mg / kg, the C60 concentration of arecoline was significantly higher. max T max T 1 / 2 Both AUC and AUC increased significantly, with increases of 4.5 times, 5.9 times, 2.1 times, and 21.8 times, respectively.

[0085] Table 5 Comparison of pharmacokinetic parameters of arecoline and drug compositions containing arecoline (n=3, Mean±SD)

[0086]

[0087] Example 5

[0088] Absorption rates of arecoline and its combination in SD rats after oral administration at different dosages

[0089] (1) Experimental methods

[0090] Twenty-four male SPF-grade SD rats, weighing 260g, were randomly divided into eight groups of three. Each group was administered arecoline (100mg / kg), Composition 1 (arecoline 50mg / kg and magnolol 50mg / kg), Composition 2 (arecoline 300mg / kg and magnolol 100mg / kg), Composition 3 (arecoline 500mg / kg and magnolol 50mg / kg), and Composition 4 (arecoline 750mg / kg and magnolol 50mg / kg) to the rats via gavage. Approximately 0.2mL of blood was collected from the retroocular venous plexus of the rats 10 minutes after administration. The blood samples were placed in 1.5mL centrifuge tubes pretreated with EDTA and centrifuged at 5000r / min for 15min at 4°C. The supernatant was then used to determine the plasma drug concentration.

[0091] (2) Experimental Results

[0092] The area under the curve ratio of arecoline to arecoline in the composition corresponding to the pharmacokinetic results is shown in the figure. Figure 2 When composition 3 was administered, the area under the curve for arecoline was the largest, indicating that the bioavailability of arecoline was increased by the highest rate, which was 38.8 times that of arecoline. When compositions 1, 2, and 4 were administered, the bioavailability was increased by 15 times, 20.4 times, and 19.6 times that of arecoline, respectively, indicating that the bioavailability of arecoline in the compositions was significantly improved.

[0093] References

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[0105]

[12] Chinese Patent CN114451575A

[0106]

[13] Chinese Patent CN106561660A

[0107]

[14] Chinese Patent CN113812665A

[0108]

[15] Chinese Patent CN105123700A

[0109]

[16] Chinese Patent CN101428027B

[0110]

[17] Chinese Patent CN101411705B

[0111]

[18] Chinese Patent CN107982264A

[0112]

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Claims

1. A pharmaceutical composition for improving the oral bioavailability of arecoline, characterized in that, The pharmaceutical composition comprises a combination of arecoline and magnolol; the weight ratio of arecoline to magnolol in the combination is 15:1 to 1:

10.

2. The pharmaceutical composition according to claim 1, characterized in that, The arecoline mentioned is a pharmacologically acceptable salt.

3. The pharmaceutical composition according to claim 1, characterized in that, The pharmacologically acceptable salts of arecoline are its hydrochloride, nicotinate, citrate, bisulfate, maleate, hydrobromide, hydroiodide, nitrate, or oxalate.

4. The pharmaceutical composition according to claim 1, characterized in that, The magnolol is one or more of a monomer, salt or eutectic.

5. The pharmaceutical composition according to any one of claims 1 to 4, characterized in that, The pharmaceutical composition is prepared into an oral dosage form using conventional methods, with the addition of pharmaceutically acceptable excipients.

6. The pharmaceutical composition according to claim 5, characterized in that, The oral dosage forms mentioned are tablets, emulsions, capsules, pills, oral liquid preparations, granules, powders, ointments, microspheres, microcapsules, sustained-release preparations, or controlled-release preparations.

7. The pharmaceutical composition according to claim 1, characterized in that, The daily dosage of the drug composition is in the range of 5 mg to 1000 mg.

8. The pharmaceutical composition according to any one of claims 1-7, characterized in that, The pharmaceutical composition is used as a combination of arecoline alone and magnolol, or as a mixture of arecoline and magnolol.

9. Use of the pharmaceutical composition according to any one of claims 1-8 in the preparation of a medicament for treating tapeworm infection, abdominal distension, diarrhea, edema, cancer, Alzheimer's disease, stroke, epilepsy, and viral pneumonia.

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