A drug for treating motion sickness

Abstract

The present invention belongs to the field of pharmaceutical technology, and particularly relates to a drug for treating motion sickness. This drug is made from the following Chinese herbal medicines in parts by weight: 3-30 parts of Platycodon grandiflorum, 3-15 parts of dried ginger, 6-20 parts of Pogostemon cablin, 6-20 parts of Pueraria lobata, 3-15 parts of Chinese date, 1-9 parts of Mentha haplocalyx, and 1-9 parts of liquorice. It has the functions of tonifying qi and nourishing blood, regulating qi in the middle-jiao, removing dampness and resolving phlegm, opening the blocked channels, and ascending the lucid and descending the turbid. It has good effects in preventing and treating motion sickness and has no adverse reactions.

Description

Technical Field

[0001] The present invention relates to a drug for treating motion sickness, belonging to the technical field of medicine. Technical Background

[0002] Motion sickness (MS) refers to a disease mainly characterized by autonomic nervous system disorders such as dizziness, nausea, gastrointestinal discomfort, etc. when the body is stimulated by unaccustomed motion or environmental stimuli. There may also be balance function disorders in the central nervous system and vestibular nervous system, which can be manifested as fatigue, cold sweat, distraction of attention, etc. This disease is often induced by taking means of transportation such as cars and ships, so it is also known as "carsickness" and "seasickness", and the incidence rate can reach 80%. Motion sickness generally does not pose a serious threat to life, but it will bring a lot of pain to patients and affect their normal work and life.

[0003] At present, the main means of preventing and treating motion sickness is to take western medicine preparations. These western medicine preparations are various, such as sympathomimetic drugs, antihistamines, anticholinergic drugs, gastrointestinal motility drugs, etc.; and most of them contain sedative and parasympathetic blocker components, and taking them simultaneously with cold medicines and anti-allergy drugs can cause adverse reactions. Some patients will have drug allergy phenomena after taking drugs containing cyclizine or caffeine. Therefore, there are certain limitations and adverse reactions in clinical use, and the actual application effect is not ideal. Therefore, there is an urgent need for a drug that can effectively prevent and treat motion sickness reactions without causing adverse reactions. Summary of the Invention

[0004] The purpose of the present invention is to overcome the deficiencies of the existing drugs for treating motion sickness, and to provide a drug for treating motion sickness, which can effectively prevent and treat motion sickness without adverse reactions.

[0005] The purpose of the present invention is achieved as follows:

[0006] A drug for treating motion sickness is mainly made from Chinese herbal medicines such as Platycodon grandiflorum, Pogostemon cablin, Pueraria lobata, Drynaria fortunei, Chinese date, Mentha haplocalyx, and Glycyrrhiza uralensis.

[0007] For the above-mentioned drug for treating motion sickness, good curative effects can be achieved when the dosages of each Chinese herbal medicine are within the following ranges:

[0008] Platycodon grandiflorum 3 - 30 parts, Drynaria fortunei 3 - 15 parts, Pogostemon cablin 6 - 20 parts, Pueraria lobata 6 - 20 parts

[0009] Chinese date 3 - 15 parts, Mentha haplocalyx 1 - 9 parts, Glycyrrhiza uralensis 1 - 9 parts

[0010] Preferably:

[0011] Platycodon grandiflorum 12 parts, Drynaria fortunei 6 parts, Pogostemon cablin 9 parts, Pueraria lobata 9 parts

[0012] 6 parts jujube 3 parts licorice 3 parts mint

[0013] More preferably:

[0014] 20 parts Platycodon grandiflorum 6 parts Dried ginger 9 parts Pueraria root 3 parts Mint

[0015] The above-mentioned drug for treating motion sickness can be prepared into any conventional preparation for pharmaceutical use by conventional methods of traditional Chinese medicine preparation. For example, the raw materials can be crushed and mixed to form a powder for oral administration; the raw materials can also be decocted, concentrated, filtered, and made into an oral liquid, syrup, or mixture; but in order to better exert the efficacy of the raw materials of the drug, it is preferred to extract the raw materials with water, filter, concentrate, dry, and add auxiliary materials to make granules; but this does not limit the scope of protection of the present invention.

[0016] The medicine of the present invention can be prepared by the following method:

[0017] 1) The Chinese herbal medicines in the weight ratio are decocted twice, 8-15 times the amount of water is added for the first time, and decocted for 1-2 hours, and 8-12 times the amount of water is added for the second time, and decocted for 0.5-2 hours, the medicinal liquids are combined, filtered, and the filtrate is concentrated to a relative density of 1.10-1.15 (60°C), ethanol is added to make the alcohol content reach 50%-90%, precipitated, and allowed to stand for 12-36 hours, and the supernatant is absorbed to obtain a water extract; concentrated, dried, and crushed to obtain a dry paste powder;

[0018] 2) The obtained dry paste powder is made into any pharmaceutical preparation.

[0019] In the above preparation method, preferably, when water is added for extraction in step 1), 12 times the amount of water is added for the first time and boiled for 2 hours, and 10 times the amount of water is added for the second time and boiled for 1 hour; when ethanol is added for precipitation, the alcohol content reaches 70% and is allowed to stand for 24 hours.

[0020] The above-mentioned method of taking the drug for treating motion sickness is that the prepared preparation is taken orally one day before and during boarding a vehicle, and the daily dosage is taken orally twice, once in the morning and once in the evening or one hour before boarding a vehicle.

[0021] The above Chinese herbal medicine parts are weight parts, which are calculated based on crude drugs. In the present invention, if the weight is in grams, the composition is the daily dosage for adults. During production, it can be increased or decreased according to the corresponding proportion. For example, large-scale production can be in kilograms or tons. The weight can be increased or decreased, but the weight ratio of the crude drugs between the Chinese herbal medicines remains unchanged, and the daily dosage for adults remains unchanged.

[0022] So far, the present invention has been completed. The drug of the present invention has good effects in preventing and treating motion sickness and has no adverse reactions. Each Chinese herbal medicine raw material used in the present invention is a raw material that can be used both as food and medicine, and there is no safety concern.

[0023] The present invention is obtained through a large number of human experience studies, process studies, and pharmacodynamic experiments under the guidance of traditional Chinese medicine theory. Traditional Chinese medicine believes that MS is caused by the deficiency of qi and blood in the body, the brain lacking nourishment, and at the same time, the transportation of body fluids is unfavorable, resulting in the production of phlegm-dampness. The phlegm-turbidity blocks the interior, the qi movement is unfavorable, and when encountering external factors such as bumps, the wind qi disturbs upward, causing the qi movement of the triple energizer to be disordered, making the phlegm, water, and food press on the qi, the clear qi not rising, the turbid yin not descending, the water-dampness stagnating internally, and the clear orifices being obstructed and thus the disease occurs. The treatment principle is to supplement qi and nourish blood, soothe the middle qi, eliminate dampness and phlegm, and open up the blocked channels.

[0024] Platycodon grandiflorum is the sovereign drug in the present invention. "Newly Revised Materia Medica": "It is mainly used for chest and hypochondrium pain like being stabbed by a knife, abdominal distension, gurgling bowel sounds, panic and palpitations. It benefits the five zang-organs and the intestines and stomach, nourishes qi and blood, dispels cold, wind, and dampness arthralgia, warms the middle energizer to promote digestion, treats sore throat and pharynx pain, and expels toxic substances." "Japanese Pharmacopoeia": "It can descend all qi, stop cholera with cramps, relieve abdominal pain and distension, tonify the five kinds of fatigue, nourish qi, expel pathogenic factors, dispel dampness, replenish deficiency, eliminate phlegm, break masses, nourish blood, drain pus, supplement internal leakage, and treat throat obstruction and alkali poisoning, which can be relieved by white rice porridge." "Comprehensive Outline of Materia Medica": "It is the key drug for promoting the qi of the lung, dredging the pharynx and diaphragm, soothing the middle qi, and resolving stagnant phlegm." "Explanation and Exploration of Materia Medica": "It can descend all qi,... If there is phlegm, water, and food pressing on the qi, only Platycodon grandiflorum can open up the blocked channels, lift the qi upward, and enable the phlegm, water, and food to descend."

[0025] Pueraria lobata and Chinese date are the ministerial drugs together. Pueraria lobata has the functions of relieving muscle fever, lifting yang to stop diarrhea, and dredging meridians and collaterals. It is commonly used for headache, stiffness and pain in the nape and back, dizzy headache, and chest impediment pain. "Just and Right Materia Medica": "Pueraria lobata can most effectively lift the clear yang qi of the spleen and stomach." "Treatise on Febrile Diseases": "It is the main drug for the yangming meridian. Exactly because the exterior cold is overly stagnated outside, the yang qi of the stomach cannot spread, so this light and ascending drug is used to quickly move the clear yang qi, defend against the exterior cold, so that the exterior pathogen is resolved and the yang qi of the stomach is relaxed,... It is also used to treat vomiting, because the stomach qi cannot spread, resulting in the inability to take in food, not generally treating vomiting caused by the upward reversal of stomach fire." Chinese date can invigorate the spleen and harmonize the stomach, replenish qi and promote fluid production, regulate nutrient qi and defensive qi, and detoxify drugs. "Shennong's Classic of Materia Medica": "It is mainly used for pathogenic factors in the heart and abdomen, calming the middle energizer to nourish the spleen, assisting the twelve meridians. It soothes the stomach qi, opens the nine orifices, supplements qi deficiency and fluid deficiency in the body, treats great fright, heaviness of the limbs, and harmonizes various drugs." "Dietary Materia Medica": "It is mainly used for supplementing body fluids, washing away pathogenic factors in the heart and abdomen, detoxifying various drug poisons, opening the nine orifices, supplementing qi deficiency, cooking and eating to nourish the intestines and stomach, and it is the first in tonifying qi and strengthening the middle energizer."

[0026] Dry ginger and pogostemon are the left medicines in combination. For dry ginger, "Shennong Ben Cao Jing" states: "It is mainly used for treating fullness in the chest, cough with counterflow qi, warming the middle-jiao, stopping bleeding, sweating, expelling wind-damp impediment, and diarrhea in the intestine." "Bie Lu" says: "It treats cold abdominal pain, sudden syncope, cholera, distension, various poisons of wind pathogen, qi stagnation in the skin, and stops spitting blood." "Rihuazi Bencao" mentions: "It dissipates phlegm and reduces qi, treats cramps, vomiting and diarrhea, cold in the abdomen and viscera, nausea and retching with regurgitation, stasis of blood, traumatic injury, stops epistaxis, relieves cold and heat toxins, promotes the appetite, and eliminates retained food." "Changsha Yaojie" states: "It dries dampness and warms the middle-jiao, promotes qi movement and reduces turbidity, suppresses counterflow qi, calms cough, lifts sunken qi, and stops slippery diarrhea." For pogostemon, "Bie Lu" says: "It treats edema due to wind-water, removes foul qi, and treats cholera and heart pain." "Materia Medica Illustrated" mentions: "It is the most important medicine for treating vomiting and counterflow of the spleen and stomach." "Zhenzhunang" states: "It supplements the defensive qi, benefits the stomach qi, promotes food intake, and also treats vomiting and cholera."

[0027] Mentha haplocalyx and licorice are the envoy medicines in combination. "Yaoxing Lun" states: "It removes stuffiness, induces sweating with toxin, breaks blood and stops dysentery, and promotes the flow of joints." "Qianjin Yifang·Shizhi" says: "It expels kidney qi and makes the breath fragrant and clean. It mainly dispels pathogenic toxins and eliminates fatigue." "Tang Bencao" mentions: "It mainly treats wind by thieves, induces sweating. (It treats) foul qi, abdominal distension, cholera, indigestion of retained food, and reduces qi." "Rihuazi Bencao" states: "It treats aphonia due to stroke, expectorates phlegm. Removes wind by thieves. Treats distension and fullness in the heart and abdomen. Reduces qi, eliminates retained food, and treats headache due to wind pathogen, etc." "Diannan Bencao" mentions: "It clears wind pathogen in the upper part of the head, stops headache, dizziness, fever, and eliminates wind-phlegm." Licorice invigorates the spleen and replenishes qi, resolves phlegm and stops cough, and harmonizes various medicines. It is commonly used for weakness of the spleen and stomach, lassitude and fatigue, palpitations and shortness of breath, and acute pain in the epigastric and abdominal regions with cramps.

[0028] When the various medicines of the present invention are used in combination, they together achieve the effects of tonifying qi and nourishing blood, regulating qi in the middle-jiao, removing dampness and resolving phlegm, opening the blocked channels, lifting the clear and lowering the turbid. The effects of preventing and treating motion sickness are good and there are no adverse reactions.

[0029] To better understand the present invention, the beneficial effects of the present invention in treating and preventing motion sickness are further elaborated through pharmacodynamic experiments and clinical studies below. The following experiments are intended to further illustrate the effects of the present invention, rather than limiting the present invention.

[0030] Weigh 12 kg of platycodon grandiflorum, 6 kg of dry ginger, 9 kg of pogostemon, 9 kg of pueraria lobata, 6 kg of Chinese date, 3 kg of licorice, and 3 kg of mentha haplocalyx, and decoct them together with water twice. For the first time, add 10 times the amount of water and decoct for 2 hours; for the second time, add 8 times the amount of water and decoct for 1 hour. Combine the decoctions, filter, take the filtrate, concentrate it to a relative density of 1.12 (at 60 °C), add ethanol to make the ethanol content reach 70%, precipitate, stand for 24 hours, draw off the supernatant, recover ethanol, concentrate, dry, and pulverize to obtain dry extract powder;

[0031] Verify the beneficial effects of the present invention in treating and preventing motion sickness.

[0032] Shandong Academy of Medical Sciences, Center for Drug Safety Evaluation

[0033] 1. Test articles, negative control, and positive control

[0034] 1.1 Basic Information

[0035] 1.1.1 Test Substance

[0036] Name: The dry extract powder of the present invention

[0037] Specification: 250 g / bag (each g of dry extract powder corresponds to 4.06 g of crude drug).

[0038] Batch Number: 202301

[0039] Appearance: Medium brown powder, odorless, slightly pungent

[0040] Expiry Date: 2025.01

[0041] Processing Enterprise: Shandong Mingren Frida Pharmaceutical Co., Ltd.

[0042] 1.1.2 Solvent

[0043] Name: Distilled water

[0044] Specification: 25 L / barrel

[0045] Batch Number: 20230227

[0046] 1.2 Preparation, Distribution and Handling of Test Substance Solution

[0047] 1.2.1 Preparation Method of Test Substance

[0048] High-dose test substance: 1.6 g of crude drug / ml (0.394 g of dry extract powder / ml): Weigh about 3.94 g of dry extract powder (16.0 g of crude drug), place it in a calibrated beaker, slowly stir and dilute it to 10 ml with distilled water, and stir evenly to obtain a test substance solution with a concentration of 0.394 g / ml (1.6 g of crude drug / ml).

[0049] Medium-dose test substance: 0.8 g of crude drug / ml (0.197 g of dry extract powder / ml): Weigh about 1.97 g of dry extract powder (8.0 g of crude drug), place it in a calibrated beaker, slowly stir and dilute it to 10 ml with distilled water, and stir evenly to obtain a test substance solution with a concentration of 0.197 g / ml (0.8 g of crude drug / ml).

[0050] Low-dose test substance: 0.4 g of crude drug / ml (0.0985 g of dry extract / ml): Weigh about 0.985 g of dry extract powder (4.0 g of crude drug), place it in a calibrated beaker, slowly stir and dilute it to 10 ml with distilled water, and stir evenly with a magnetic stirrer to obtain a test substance solution with a concentration of 0.0985 g / ml (0.4 g of crude drug / ml).

[0051] 1.2.2 Distribution: Distributed to the testers before each administration.

[0052] 1.2.3 Disposal: The remaining samples after each administration are returned to the sample preparation room and disposed of as medical waste.

[0053] SD rats are one of the recognized standard rodent animals in pharmacodynamic experimental studies, with a clear genetic background, stable genetic traits, a large amount of background information and research basis, and sufficient animal supply. Therefore, SD rats are used as experimental animals in this experiment.

[0054] Gender, quantity, age in weeks, weight range:

[0055] At reception: Female: 40 rats, 5 - 6 weeks old, 180 - 220.2 g.

[0056] Male: 40 rats, 5 - 6 weeks old, 180.7 - 211.7 g.

[0057] At the end of quarantine: Female: 40 rats, 6 - 7 weeks old, 210.6 - 242.1 g.

[0058] Male: 40 rats, 6 - 7 weeks old, 231.3 - 262.6 g.

[0059] Animal source: Jinan Pengyue Laboratory Animal Breeding Co., Ltd.

[0060] Quality certificate number of experimental animals: 370726231101036112

[0061] Production license number of experimental animals; SCXK(Lu) 2022 0006, Validity period: October 26, 2022 - October 25, 2027.

[0062] 2.3 Breeding facilities

[0063] Animals are bred in the barrier facilities of the test institution. The set temperature is 20 - 26 °C, the actual temperature is 20.1 - 25.9 °C, and the daily temperature difference ≤ 4 °C; the set relative humidity is 40% - 70%, the actual relative humidity is 41.3% - 67.6%; the number of air changes ≥ 15 times; the minimum static pressure difference in the interconnected areas ≥ 10 Pa; the air flow velocity ≤ 0.2 m / s; the noise ≤ 60 dB; the minimum working illuminance ≥ 200 lx; the animal illuminance is 15 - 20 lx; the day-night light-dark alternation time is 10 h / 14 h. License number for the use of experimental animals: SYXK(Lu) 20220005, Validity period: March 9, 2022 - March 8, 2027.

[0064] Environmental testing: In February 2023, the Shandong Laboratory Animal Center was commissioned to test the animal breeding facilities. The test results met the requirements of the barrier environment facilities in GB 14925-2010 "Laboratory Animal Environment and Facilities". The report date was February 20, 2023, and the report number was H20230003.

[0065] 2.4 Breeding cages

[0066] Mouse boxes, specifications: length × width × height = 320 × 180 × 150 mm, produced by Suzhou Jiahong Metal Technology Co., Ltd., production license: SCXK (Su) 2009-0004.

[0067] Breeding density: ≤ 5 animals / box.

[0068] Daily replacement: Breeding boxes 2 times / week or as necessary; breeding box mesh covers 1 time / week or as necessary.

[0069] 2.5 Feed

[0070] Name: SPF mouse and rat growth and reproduction compound feed.

[0071] Batch number: 23073113.

[0072] Experimental animal feed quality certificate number: 230800530.

[0073] Source: Keao Xieli (Tianjin) Feed Co., Ltd.

[0074] Production license number: SCXK (Jin) 2020-0004, validity period: October 20, 2020 - October 19, 2025.

[0075] Feeding: Add once every 2 - 3 days or as necessary, and animals can freely ingest.

[0076] Quality control: This batch of feed was tested by the production enterprise for nutritional components such as crude protein, crude fat, crude fiber, moisture, calcium, total phosphorus, and crude ash, and the production enterprise commissioned PONY Testing Technology (Tianjin) Co., Ltd. and Qingdao Huace Testing Technology Co., Ltd. to test chemical pollutants such as arsenic, lead, cadmium, mercury, hexachlorocyclohexane, DDT, and aflatoxin B1. The test results met the national standards.

[0077] 2.6 Drinking water

[0078] Name: Experimental animal drinking water (barrier)

[0079] Source: MN-LM200J experimental animal drinking water dispenser

[0080] Drinking water: Replace once every 2 - 3 days or as necessary, and animals can freely drink.

[0081] Quality Control: In March 2023, Shandong Quancheng Testing Technology Co., Ltd. was commissioned to test the total coliform group, total colony count, cyclic nitrogen, chromium (hexavalent), nitrate (in terms of N), color, turbidity, odor and taste, pH, aluminum, iron, copper, zinc, chloride, sulfate, and total hardness (in terms of CaCO3) in drinking water. Each indicator meets the requirements of GB5749-2006 "Sanitary Standards for Drinking Water".

[0082] 2.7 Animal Receipt, Identification and Observation during Quarantine Period

[0083] 2.7.1 Receiving: After the animals are purchased, they enter the functional laboratory for quarantine through the transfer window. After passing the inspection, they are placed in the breeding box and put on the shelf for breeding.

[0084] 2.7.2 Identification

[0085] House number: White house number, including subject number, subject name, subject person in charge and telephone number, experimental animals, number of animals, animal receipt date, quarantine end date, feeding room, quarantine observer, quarantine person in charge and telephone number.

[0086] Cage card identification: White cage card, identification includes subject number, experimental animal, cage number, gender, identification, animal receiving day, and subject person in charge.

[0087] Animal identification: The tails of mice and rats were automatically numbered using an automatic tail marking instrument, and both sexes were numbered 1-40.

[0088] 2.7.3 Observation

[0089] Observation time: 7 days

[0090] General physical signs: A detailed physical examination is conducted on the day of animal receipt and at the end of quarantine. The animals are observed once a day by the cage at other times. Observation indicators: Whether the animal's coat, skin, eyes, ears, nose, mouth, limbs, genitals, anus, mental state, etc. are abnormal.

[0091] Body weight determination: Animals were weighed once on the day of receipt and at the end of quarantine.

[0092] Quarantine results: Weight: 80 animals, at the beginning of quarantine, female animals were 180-220.2g, male animals were 180.7-211.7g; at the end of quarantine, female animals were 210.6-242.1g, male animals were 231.3-262.6g. General signs: The coat, skin, eyes, ears, nose, mouth, limbs, genitals, anus, mental state, etc. of the 80 animals were normal, and their food and water intake were normal.

[0093] Quarantine conclusion: qualified.

[0094] The motion sickness simulator was adapted from the report by Crampton et al.

[0095] 1. Animal grouping, identification, and numbering

[0096] 1.1 Grouping

[0097] Animals that passed quarantine were selected, excluding those with relatively large or small body weights. The weight difference within the same sex should be within 20% of the average weight. A total of 50 animals were selected, with 25 males and 25 females. Female animals were sorted in ascending order of body weight, and male animals were sorted in descending order of body weight. According to the Latin method, they were divided into 5 groups: negative control group, model control group, low-dose dry extract powder group, medium-dose group, and high-dose group, with 5 animals per sex per group.

[0098] 1.2 Identification

[0099] 1.2.1 Doorplate identification: white doorplate, with identification content including: project number, project name, experimental animals, number of animals, administration time, end date of breeding, breeding room, observer of administration, project leader, and phone number.

[0100] 1.2.2 Cage card identification: After grouping, the negative control group used white cage cards, the model control group used blue cage cards, the low-dose group used green cage cards, the medium-dose group used yellow cage cards, and the high-dose group used red cage cards. The content included: project number, experimental animals, administration route, group, cage number, sex, identification, number, administration time, and project leader.

[0101] 1.2.3 Animal identification: Except for retaining the tail identification during the quarantine period, the head, neck, back, and tail were respectively stained with a coloring pen, and the 5th animal was not stained.

[0102] 1.3 Numbering: Arabic numerals were used for numbering, with a total of 4 digits. The first digit represents the group, the second digit represents the sex, and the third and fourth digits represent the animal number within the group (01, 02, 03...). The animal group, sex, number, and numbering are shown in Table 1.

[0103] Table 1 Animal group, sex, number, and numbering table

[0104] 2. Administration dose, route, method, frequency, duration, and reasons for selection

[0105] 2.1 Administration dose

[0106] 2.1.1 Design basis for the test article dose

[0107] ① Human clinical dose and administration method: Take 48 g of the medicinal material once, which is equivalent to 11.82 g of dry extract powder.

[0108] The inventor of the present invention takes 48 g of the medicinal material once, which is equivalent to 11.82 g of dry extract powder. Calculated according to a body weight of 70 kg, the human single-dose is approximately 48 g / 70 kg = 0.6857 g of crude drug / kg / d.

[0109] Estimation of equivalent dose in rats: The approximate calculation formula for body surface area is lgS = 0.8762 + 0.698lgW, where S is the body surface area (cm 2 ), and W is the body weight (g). The body weights of humans and rats are calculated as 70 kg and 250 g respectively, and their body surface areas are 1.8117 m 2 and 0.0355 m 2 . According to the body surface area, the equivalent dose of rats is estimated as follows: equivalent dose of rats = human daily dose (g / d) / human body surface area (m 2 ) × rat body surface area (m 2 ) / rat body weight (kg) = 48 g / 1.8117 m 2 × 0.0355 m 2 / 0.25 kg - 3.762 g crude drug / kg / d.

[0110] 2.1.2 Dosage design of test article

[0111] Refer to the above calculation, and the dosage design is as follows:

[0112] High dose: 16.0 g crude drug / kg / d, about 23.33 times the human clinical single-dose (4.25 times the equivalent dose based on body surface area).

[0113] Medium dose: 8.0 g crude drug / kg / d, about 11.67 times the human clinical single-dose (2.13 times the equivalent dose based on body surface area).

[0114] Low dose: 4.0 g crude drug / kg / d, about 5.83 times the human clinical single-dose (1.06 times the equivalent dose based on body surface area).

[0115] 2.1.3 Design and basis of negative control

[0116] The test article is prepared with distilled water, so distilled water is selected as the negative control.

[0117] 2.2 Route of administration: The clinical route is oral administration, so intragastric administration is used in this experiment.

[0118] 2.3 Administration method: Intragastric administration. The negative control group and the model control group are given the same volume of distilled water, and the administration volume is 10 ml / kg.

[0119] 2.4 Administration frequency: One intragastric administration 30 minutes before establishing the motion sickness model.

[0120] 3. Establishment of a rat model of simulated motion sickness

[0121] After 30 minutes of gavage in each group of rats except the blank control group, the rats were placed in a motion sickness simulator. The device rotated clockwise around the vertical axis and accelerated at an angular acceleration of 16° / S 2 to 120° / S 2 , and then decelerated at an angular deceleration of 48° / S 2 to zero, with alternating acceleration and deceleration for 30 minutes, and the motion sickness response index was statistically analyzed.

[0122] 4. Scoring criteria for motion sickness response index

[0123] As is well known to those skilled in the art, since rodents do not have a vomiting reflex, the change in the motion sickness response index has a good correlation with the severity of gastrointestinal reactions caused by acceleration exposure in rodents, and can be used as an indicator for judging the severity of motion sickness in rodents.

[0124] The scoring criteria for the motion sickness response index include: each defecation granule is scored 1 point, and 0 points if none; urination is scored 1.2 points if present, and 0 points if none; severe piloerection is scored 1.2 points, mild piloerection is scored 0.6 points, and 0 points if none; tremor is scored 1.2 points, and 0 points if none; the motion sickness response index is the sum of the scores of these four parts.

[0125] 5. Results

[0126] After the establishment of the motion sickness rat model and stimulation, the motion sickness response index of the rats in the model group was significantly higher than that in the blank control group, and the difference was statistically significant (P<0.01). The motion sickness response indices of the low, medium, and high dose groups of the present invention were all lower than those in the model group (P<0.01), and there was no significant difference in the motion sickness response indices of the low, medium, and high dose groups of the present invention compared with the blank control group (P>0.05). Conclusion: The low, medium, and high doses of the present invention have significantly improved the ability of rats to resist simulated motion sickness stimulation. See Table 2.

[0127] Table 2 Effects of dry extract powder on the motion sickness response index of rats stimulated by simulated motion sickness

[0128] ﹡﹡: VS model group, P<0.01; ﹟: VS blank control group, P<0.01; ﹟﹟: VS blank control group, P>0.05.

[0129] Clinical research of the present invention

[0130] I. Preparation of test articles:

[0131] 1) Weigh 12 kg of Platycodon grandiflorum, 6 kg of dried ginger, 9 kg of Pogostemon cablin, 9 kg of Pueraria lobata, 6 kg of Chinese dates, 3 kg of liquorice, and 3 kg of Mentha haplocalyx. Decoct them together with water twice. For the first time, add 10 times the amount of water and decoct for 2 hours. For the second time, add 8 times the amount of water and decoct for 1 hour. Combine the decoctions, filter, take the filtrate, concentrate it to a relative density of 1.12 (60 °C), then dry it under vacuum and pulverize to obtain 11.7 kg of dry extract powder.

[0132] 2) Add 8.3 kg of dextrin to the dry extract powder, mix well, add an appropriate amount of purified water, make soft materials, granulate through a 20-mesh sieve, dry, and screen the granules through an 18-mesh sieve.

[0133] 3) Pack them into 10 g / bags to obtain the granule agent.

[0134] II. Clinical Research

[0135] 1. Case Source and Number of Cases

[0136] Select 40 employees and their relatives of the company who have a history of motion sickness and no physical diseases.

[0137] 2. Diagnostic Criteria

[0138] Meet the "Diagnostic Criteria for Motion Sickness: Consensus Document of the Classification Committee of the Bárány Society":

[0139] ① The onset occurs several minutes to several hours after taking means of transportation such as ships, vehicles, and airplanes.

[0140] ② First, dizziness and lassitude appear, and then headache, salivation at the corners of the mouth, nausea, vomiting, mental depression, and pale complexion occur. In severe cases, cold sweats, decreased blood pressure, tachycardia or bradycardia may occur. Severe vomiting can also cause dehydration, acidosis, etc.

[0141] ③ After stopping the movement, the symptoms disappear within a short time.

[0142] ④ There is a similar medical history during previous travels and it recurs frequently.

[0143] 3. Inclusion Criteria

[0144] ① Those who meet the above diagnostic criteria;

[0145] ② Those without serious underlying diseases such as chronic diseases;

[0146] ③ Those who are aware of the content and purpose of the experiment and voluntarily sign the informed consent form.

[0147] 4. Exclusion Criteria

[0148] ① Those who do not meet the above inclusion criteria;

[0149] ② Those who have used vestibular inhibitors within the past week, or those who have consumed beverages containing alcohol, caffeine, etc. that affect the activity of the autonomic nervous system within the past week;

[0150] ③ Those with a history of head or ear trauma or surgery;

[0151] ④ Those with a history of middle ear, inner ear or vestibular diseases and vertigo, such as otitis media, BPPV, Meniere's disease, vestibular neuritis or labyrinthitis, superior semicircular canal dehiscence syndrome, etc.

[0152] 5. Withdrawal criteria

[0153] ① Those who withdraw from this study due to any subjective or objective factors during the study;

[0154] ② Those who do not follow the doctor's advice for treatment, resulting in inability to judge the curative effect or incomplete data.

[0155] 6. Motion sickness scoring criteria

[0156] In this study, the clinical efficacy of this therapy was comprehensively analyzed by comparing the changes in the Graybiel motion sickness scores of the subjects before and after treatment. The symptom scores include 7 dimensions: vomiting symptoms (specific symptoms), skin color (lip color), cold sweating, salivation, drowsiness, pain, and central nervous symptoms. Among them, the first 5 dimensions are assigned values according to the degree of symptom manifestation, which are specific symptoms (16 points), severe (8), moderate (4), mild (2), additional symptoms (1), and the last 2 dimensions only have additional symptoms (1). The total score is the sum of the scores of each dimension. The specific content is shown in Table 3.

[0157] Table 3 Motion sickness degree scoring table

[0158] Type Specific symptom: 16 points Severe: 8 points Moderate: 4 points Mild: 2 points Additional symptom: 1 point Vomiting symptom Vomiting / retching Nausea (severe / obvious, general) Nausea (slight) Upper abdominal discomfort Response in the upper abdomen (hiccups, etc.) Skin color (lip color) Pale Pale and dull Pale Flushed face Cold sweat Severe / obvious General Slight Saliva secretion Severe / obvious General Slight Drowsiness Severe / obvious General Slight Pain / / / Headache Central nervous system symptom Dizziness: very dizzy with eyes open, obviously dizzy with eyes closed

[0159] 7. Clinical research methods

[0160] Forty employees of this company and their relatives without physical diseases took the same bus for 1 hour before treatment to conduct motion sickness scoring.

[0161] Seven days later, they were randomly divided into two groups: 20 cases in the treatment group, 9 males and 11 females; aged 9 - 60 years old; 20 cases in the control group, 10 males and 10 females; aged 10 - 57 years old; all had no history of gasoline allergy. There was no significant difference in age and gender between the two groups of patients (P > 0.05). Before treatment, the motion sickness score of the control group was (10.64 ± 9.53) points, and that of the treatment group was (10.68 ± 9.51) points. There was no significant difference in the general data between the two groups (P > 0.05).

[0162] Two groups of observed subjects took the same passenger bus for 1 hour. One day before taking the bus, the treatment group took the granule orally, 2 bags per day, 1 bag each in the morning and evening, and 2 bags were taken orally at one time 1 hour before taking the bus. The control group took 1 Dramamine (45 mg / capsule) orally within 1 hour before getting on the bus. The method of observing the subjects was to travel with them, and statistical analysis was carried out.

[0163] 8. Treatment Results

[0164] Before treatment, the motion sickness score of the control group was (10.64 ± 9.53) points, and that of the treatment group was (10.68 ± 9.51) points. There was no significant difference between the two groups (P > 0.05). After treatment, the score of the control group was (7.21 ± 4.81) points, P < 0.05, and the score of the treatment group was (3.64 ± 5.16) points, P < 0.01. The score of the treatment group was significantly lower than that of the control group, and there was a significant difference in the severity grading of motion sickness between the two groups (P < 0.01). The results are shown in Table 4.

[0165] Table 4 Graybiel Motion Sickness Scores of Two Groups of Patients (points)

[0166] Group Before treatment After treatment Control group 10.64±9.53 7.21±4.81* * Observation group 10.68±9.51 3.64±5.16* #

[0167] Note: For within-group comparison, *P < 0.01, **P < 0.05; compared with the control group at the same time, #P < 0.05. Specific Embodiments

[0168] The present invention will be further illustrated below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. After reading the present invention, various equivalent modifications made by those skilled in the art fall within the scope defined by the appended claims of this application.

[0169] The weights in the following embodiments are 1000 times the prescription amount for one person per day.

[0170] Example 1: Preparation of the Granule of the Drug of the Present Invention

[0171] Weigh the following raw materials by weight:

[0172] Platycodon grandiflorum 15 kg, Dry Ginger 7.5 kg, Pogostemon cablin 10 kg, Pueraria lobata 10 kg, Chinese Date 7.5 kg, Mentha haplocalyx 4.5 kg, Licorice Root 4.5 kg

[0173] The above raw materials are prepared by the following method:

[0174] The above seven herbs are decocted twice with water. For the first time, add 15 times the amount of water and decoct for 2 hours. For the second time, add 12 times the amount of water and decoct for 2 hours. Combine the decoction liquids, filter, take the filtrate, concentrate it to a relative density of 1.15 (60 °C), add ethanol to make the ethanol content reach 90%, precipitate, let it stand for 12 - 36 hours, draw off the supernatant, recover the ethanol, concentrate, dry it under vacuum, pulverize it to obtain dry extract powder;

[0175] 2) Mix the obtained dry extract powder thoroughly with an appropriate amount of dextrin, granulate with ethanol solution as the binder, and dry to obtain the granule.

[0176] Example 2: Oral liquid of the medicine of the present invention

[0177] Weigh the following raw materials by weight:

[0178] Platycodon grandiflorum 15 kg, Dry Ginger 7.5 kg, Pogostemon cablin 10 kg, Pueraria lobata 10 kg, Jujube 7.5 kg, Mentha haplocalyx 4.5 kg, Licorice root 4.5 kg, total 59 kg

[0179] The above raw materials are prepared by the following method:

[0180] The above seven herbs are crushed into coarse powder, using 50% ethanol as the solvent, impregnate for 24 hours, then evenly load into the percolator, about 10 cm thick, press evenly with a T-shaped rod, and then load layer by layer according to the above operation, using 50% ethanol as the solvent, slowly percolate at a speed of about 0.15 liters per minute, collect about 50 liters of percolate, recover ethanol under reduced pressure, and concentrate to about 15 liters. Take it out, add water to 20 liters, boil for 30 minutes, let it stand for 48 hours, filter, wash the filter residue with a small amount of water, incorporate the washing liquid into the filtrate, concentrate under reduced pressure to about 20 liters, add 60 grams of sodium benzoate, stir well, let it stand for 24 hours, filter, and subpackage, 10 ml / bottle. Thus obtained.

[0181] Dosage and administration: Take orally one day before taking a vehicle, 2 bottles a day, 1 bottle each in the morning and evening, and 2 bottles at one time orally 1 hour before taking a vehicle.

[0182] Example 3: Syrup of the medicine of the present invention

[0183] Weigh the following raw materials by weight:

[0184] Platycodon grandiflorum 10 kg, Dry Ginger 6 kg, Pogostemon cablin 9 kg, Pueraria lobata 9 kg, Jujube 6 kg, Mentha haplocalyx 2 kg, Licorice root 1 kg

[0185] The above raw materials are prepared by the following method:

[0186] The above seven herbs are decocted twice with water. For the first time, add 10 times the amount of water and decoct for 3 hours. For the second time, add 8 times the amount of water and decoct for 1 hour. Combine the decoctions, filter, let the filtrate stand for more than 6 hours, take the supernatant, and concentrate to an appropriate amount. Separately, take 650 g of sucrose, add water and boil to make a syrup, mix it with the above concentrated solution, boil, cool, add 50 g of sodium benzoate, add water to 20000 ml, stir well, let stand, filter, divide into portions, 10 ml per bottle, and you will get it.

[0187] Example 4: Preparation of tablets of the drug of the present invention

[0188] Weigh the following raw materials by weight:

[0189] Platycodon grandiflorum 20 kg, dried ginger 6 kg, kudzu root 9 kg, mint 3 kg

[0190] Prepare the above raw materials by the following method:

[0191] The above seven herbs are decocted twice with water. For the first time, add 8 times the amount of water and decoct for 2 hours. For the second time, add 8 times the amount of water and decoct for 2 hours. Combine the medicinal liquids, filter the medicinal liquids, take the filtrate, concentrate to a relative density of 1.1 (60 °C), add ethanol to make the alcohol content reach 70%, precipitate, let stand for 36 hours, draw off the supernatant, recover the ethanol, concentrate under reduced pressure, dry, pulverize to obtain dry extract powder; thoroughly mix the dry extract powder with an appropriate amount of sucrose powder, granulate with ethanol solution as a binder, dry, add an appropriate amount of magnesium stearate and mix well to make tablets.

[0192] Example 5: Preparation of capsules of the drug of the present invention

[0193] Weigh the following raw materials by weight:

[0194] Platycodon grandiflorum 10 kg, dried ginger 3 kg, Pogostemon cablin 20 kg, kudzu root 10 kg, Chinese date 10 kg, mint 9 kg, liquorice root 6 kg

[0195] Prepare the above raw materials by the following method:

[0196] The above seven herbs are decocted twice with water. For the first time, add 12 times the amount of water and decoct for 2 hours. For the second time, add 10 times the amount of water and decoct for 1 hour. Combine the medicinal liquids, filter the medicinal liquids, take the filtrate, concentrate to a relative density of 1.10 - 1.15 (60 °C), add ethanol to make the alcohol content reach 70%, precipitate, let stand for 24 hours, draw off the supernatant, concentrate, dry, pulverize to obtain dry extract powder; thoroughly mix the dry extract powder with an appropriate amount of microcrystalline silica, granulate with ethanol solution as a binder, dry, add an appropriate amount of magnesium stearate and mix well, and fill into hard gelatin capsules.

Claims

1. A drug for treating motion sickness, characterized in that: It is made from the following Chinese medicines in parts by weight: 12 parts of Platycodon grandiflorum, 6 parts of dried ginger, 9 parts of Poria cocos, 9 parts of Pueraria root, 6 parts of jujube, 3 parts of liquorice, and 3 parts of mint.

2. The drug for treating motion sickness according to claim 1, characterized in that: The drug may be prepared into any of granules, oral solution, syrup, or tablets.