A compound composition for preventing and treating motion sickness and a preparation method thereof

Abstract

The application provides a compound composition for preventing and treating motion sickness and a preparation method thereof, the compound composition comprises the following raw materials in parts by weight: dimenhydrinate 2-6 parts, dextroamphetamine 0.2-0.6 parts, ginger 20-50 parts, dried tangerine or orange peel 10-20 parts, privet fruit 8-15 parts, tribulus terrestris 8-15 parts, rhizoma alocasia 5-12 parts, pachystachys jamaicensis 8-15 parts, daya flower 5-10 parts, litsea cubeba 3-8 parts, kaempferia 3-8 parts, ipomoea alba 5-10 parts, menthol 0.5-3 parts; the compound composition of the application realizes the enhancement of the anti-motion effect and the offset of the side effects, and especially significantly reduces the drowsiness caused by dimenhydrinate and the potential risk of excessive nerve excitement of dextroamphetamine.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a compound composition for the prevention and treatment of motion sickness and its preparation method. Background Technology

[0002] Motion sickness, commonly known as car sickness, seasickness, or airsickness, is a series of physiological reactions that occur when the body is exposed to abnormal motion. The main symptoms include nausea, vomiting, dizziness, and cold sweats. Its pathogenesis is complex, but it is currently widely believed to be caused by conflicting signals transmitted from the vestibular, visual, and proprioceptive systems to the central nervous system.

[0003] Currently, commonly used anti-motion sickness drugs in clinical practice mainly include the following categories: 1. Antihistamines: such as dimenhydrinate, as an H1 receptor antagonist, can effectively inhibit the excitability of the vestibular nucleus and is the most widely used over-the-counter drug. However, its common side effects include drowsiness, dry mouth, and dizziness, which can affect the user's normal work, especially for drivers and those who operate precision instruments.

[0004] 2. Anticholinergic drugs: such as scopolamine, which have significant effects, but stronger side effects, including drowsiness, blurred vision, and difficulty urinating, thus limiting their use.

[0005] 3. Sympathomimetic amines: such as lisdexamine, have a central nervous system stimulant effect and can counteract the drowsiness caused by the first two types of drugs. However, they are strictly controlled psychotropic drugs and have risks of addiction, anxiety, and palpitations. Their use alone is limited.

[0006] In recent years, natural medicines have shown potential in the prevention and treatment of motion sickness. Ginger, a traditional Chinese medicine, is known as a "miracle cure for nausea." Modern research shows that ginger exerts its anti-motion sickness effects through multiple pathways, including antagonizing 5-HT3 receptors, anti-oxidation, and inhibiting gastrointestinal reactions, without the side effect of drowsiness. However, the onset speed and strength of ginger alone are sometimes insufficient for patients with severe motion sickness. Currently, there is a lack of compound preparations that combine modern chemical drugs with characteristic traditional Chinese medicines for multi-target synergistic treatment.

[0007] Therefore, there is an urgent need in this field for a drug combination regimen that can effectively and quickly relieve the core symptoms of motion sickness (nausea and vomiting), minimize side effects such as drowsiness, and has a high safety profile. Summary of the Invention

[0008] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide a compound composition for preventing and treating motion sickness and its preparation method, which addresses the problems of drowsiness caused by dimenhydrinate and potential excessive nerve excitation caused by lisdexample.

[0009] To achieve the above and other related objectives, the present invention provides a compound composition for the prevention and treatment of motion sickness, comprising, by weight, the following ingredients: Dimenhydrinate 2-6 parts, lysine dextromethorphan 0.2-0.6 parts, ginger 20-50 parts, dried tangerine peel 10-20 parts, Vitex trifolia 8-15 parts, Tribulus terrestris 8-15 parts, Acorus tatarinowii 5-12 parts, patchouli 8-15 parts, bitter orange blossom 5-10 parts, Litsea cubeba 3-8 parts, Kaempferia galanga 3-8 parts, frangipani 5-10 parts, menthol 0.5-3 parts.

[0010] The present invention also provides a method for preparing the above-described compound composition for preventing and treating motion sickness, comprising the following steps: (1) The following herbs were extracted with water: ginger, tangerine peel, vitex fruit, tribulus fruit, acorus tatarinowii, patchouli, bitter orange flower, litsea cubeba, galangal, and frangipani. The extract was filtered, the filtrate was concentrated, and dried to obtain the herbal extract. (2) The Chinese herbal extract obtained in step (1) is mixed with dimenhydrinate, lysdexample, and a pharmaceutically acceptable carrier or excipient to obtain a mixture; (3) Dissolve menthol in anhydrous ethanol and add it to the mixed powder in step (2) in the mixed state by spraying. Continue mixing to allow the ethanol to evaporate and dry to obtain the compound composition for the prevention and treatment of motion sickness.

[0011] The present invention also provides a medicament for the preparation of a drug for the prevention and / or treatment of motion sickness according to the use of the above-described compound composition.

[0012] As described above, the compound composition for preventing and treating motion sickness and its preparation method of the present invention have the following beneficial effects: The compound composition for preventing and treating motion sickness of the present invention achieves enhanced anti-motion sickness effect and offsets side effects through the synergistic effect of each active ingredient, and in particular significantly reduces the risk of drowsiness caused by dimenhydrinate and the potential for excessive nerve excitation by lisdexample.

[0013] This invention addresses the contradiction between drowsiness and addiction by introducing lysdexample, a specific prodrug, and creatively combines eleven traditional Chinese medicines to construct a novel adjuvant system that "regulates qi and eliminates dampness, opens the orifices and calms the mind." This system forms a precise relationship with the core chemical drug, synergistically enhancing efficacy and controlling side effects. Through multi-pathway synergy, it achieves a dual improvement in efficacy and safety. This complex combination, based on a profound understanding of pathogenesis and modern pharmacological verification, produces a synergistic effect of "1+1>2". Detailed Implementation

[0014] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0015] When a numerical range is disclosed herein, the range is considered continuous and includes the minimum and maximum values ​​of the range, as well as every value between the minimum and maximum values. Furthermore, when the range refers to an integer, it includes every integer between the minimum and maximum values ​​of the range. Additionally, when multiple ranges are provided to describe a feature or characteristic, the ranges may be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges to which they are included. For example, a specified range from “1 to 10” should be considered to include any and all subranges between the minimum value 1 and the maximum value 10. Exemplary subranges of the range 1 to 10 include, but are not limited to, 1 to 6.1, 3.5 to 7.8, 5.5 to 10, etc.

[0016] Furthermore, it should be understood that the one or more method steps mentioned in this invention do not preclude the existence of other method steps before or after the combined steps, or the insertion of other method steps between these explicitly mentioned steps, unless otherwise stated; moreover, unless otherwise stated, the numbering of each method step is merely a convenient tool for identifying each method step, and not for limiting the order of the method steps or limiting the scope of the invention. Changes or adjustments to their relative relationships, without substantially altering the technical content, should also be considered as within the scope of the invention.

[0017] The first aspect of this invention provides a compound composition for preventing and treating motion sickness, comprising, by weight, the following raw materials: Dimenhydrinate 2-6 parts; for example, 2-3 parts, 3-5 parts, or 5-6 parts; inhibits vestibular excitation; Lysdexamine 0.2-0.6 parts; for example, 0.2-0.3 parts, 0.3-0.5 parts or 0.5-0.6 parts; improves mental alertness and counteracts the drowsiness of dimenhydrinate; 20-50 parts of ginger; for example, 20-22 parts, 22-25 parts, 25-27 parts, 27-30 parts, 30-35 parts, 35-40 parts, 40-45 parts, or 45-50 parts; to warm the stomach and stop vomiting; 10-20 parts dried tangerine peel; for example, 10-12 parts, 12-15 parts, 15-18 parts, or 18-20 parts; regulates qi, strengthens the spleen, dries dampness, and resolves phlegm; 8-15 parts of Vitex trifolia fruit; for example, 8-10 parts, 10-12 parts or 12-15 parts; to dispel wind-heat and clear the head and eyes, targeting the core symptom of "vertigo" in motion sickness; Tribulus terrestris 8-15 parts; for example, 8-10 parts, 10-12 parts or 12-15 parts; it soothes the liver and relieves depression, dispels wind and improves eyesight, and is used for dizziness and headache due to hyperactivity of liver yang; 5-12 parts of Acorus tatarinowii; for example, 5-8 parts, 8-10 parts or 10-12 parts; it can resolve dampness, stimulate appetite, open the orifices and clear phlegm, refresh the mind and improve intelligence, targeting the pathogenesis of "phlegm and dampness obscuring the clear orifices"; Patchouli 8-15 parts; for example, 8-10 parts, 10-12 parts, or 12-15 parts; aromatic and purifying; Use 5-10 parts of bitter orange blossom; for example, 5-8 parts or 8-10 parts; it can regulate qi and relieve chest tightness, stimulate appetite and stop vomiting. Its fragrance is pleasant and helps to relieve nausea. Litsea cubeba 3-8 parts; for example, 3-5 parts, 5-7 parts or 7-8 parts; warms the middle and dispels cold, promotes qi circulation and relieves pain, and has a synergistic effect with ginger in warming the stomach and stopping vomiting; 3-8 parts of galangal; for example, 3-5 parts, 5-7 parts or 7-8 parts; warms the middle and resolves dampness, promotes qi circulation and relieves pain, and enhances the overall effect of the formula in resolving dampness and turbidity; Frangipani 5-10 parts; for example, 5-8 parts or 8-10 parts; clears heat and promotes diuresis, used for vomiting and diarrhea caused by summer heat and dampness, can balance the warming nature of the formula and prevent heat generation; Menthol 0.5-3 parts; for example, 0.5-1 part, 1-1.5 parts, 1.5-2 parts, 2-2.5 parts or 2.5-3 parts; to dispel wind-heat and clear the head and eyes.

[0018] In a preferred embodiment of the present invention, the compound composition comprises, by weight, the following raw materials: 3-5 parts of dimenhydrinate, 0.3-0.5 parts of lysadecanol, 22-30 parts of ginger, 14-18 parts of dried tangerine peel, 10-13 parts of Vitex trifolia, 10-13 parts of Tribulus terrestris, 8-10 parts of Acorus tatarinowii, 10-13 parts of patchouli, 6-8 parts of Citrus aurantium, 4-6 parts of Litsea cubeba, 4-6 parts of Kaempferia galanga, 6-8 parts of Plumeria rubra, and 1-2 parts of menthol.

[0019] In a more preferred embodiment of the present invention, the compound composition comprises, by weight, the following ingredients: 3 parts dimenhydrinate, 0.3 parts lysadecanol, 22 parts ginger, 15 parts dried tangerine peel, 12 parts Vitex trifolia, 12 parts Tribulus terrestris, 10 parts Acorus tatarinowii, 12 parts patchouli, 8 parts Citrus aurantium, 5 parts Litsea cubeba, 5 parts Kaempferia galanga, 8 parts Frangipani, and 2 parts menthol.

[0020] The pathogenesis of motion sickness is as follows: wind stirs up phlegm, dampness obstructs the middle jiao, clear yang fails to ascend, turbid yin fails to descend, and qi stagnation occurs. Treatment principles: calm wind and stop dizziness, dry dampness and resolve phlegm, harmonize the stomach and descend rebellious qi, regulate qi and open the orifices, supplemented with methods to refresh the mind.

[0021] In this invention, dimenhydrinate and ginger are used as the principal drugs, targeting the primary symptoms. Lisdexample is used as an adjuvant drug, exerting its effects of improving mental clarity and alertness, working synergistically with the principal drugs. Dimenhydrinate, from the perspective of traditional Chinese medicine theory, has a strong inhibitory effect on vestibular excitation, which can be compared to a key medicine for "calming the liver and extinguishing wind, relieving dizziness and vertigo," directly addressing the core of motion sickness, "wind-induced vertigo." Lisdexample, with its slow-release and mildly sustained central nervous system stimulant effect, plays the role of "improving mental clarity and alertness" in the formula, effectively counteracting the drowsiness caused by the principal drug dimenhydrinate, ensuring the user remains conscious. In this invention, the ginger... Ginger rhizome Recens uses fresh rhizomes, and ginger, known as the "holy medicine for vomiting," excels at "warming the stomach and stopping vomiting," effectively addressing the most prominent symptoms of motion sickness—nausea and vomiting. This trio of "principal herbs" forms a "iron triangle" for rapidly controlling the three core issues of dizziness, vomiting, and drowsiness, ensuring its effectiveness.

[0022] Tangerine peel, vitex fruit, and tribulus terrestris are used as assistant herbs to assist the principal herb and enhance its efficacy. In this invention, the tangerine peel... Citrus reticulated Pericarpium uses dried, mature pericarp. Dried tangerine peel, as the primary "assistant herb," ​​has the functions of "regulating qi and strengthening the spleen, drying dampness and resolving phlegm." It assists ginger in soothing the stomach and relieving nausea, and also assists dimenhydrinate in resolving phlegm and calming wind, thus enhancing the anti-vertigo effect of the principal herb from the root cause of "phlegm." Vitex trifolia and Tribulus terrestris: Both of these herbs enter the liver meridian and are wind-dispelling and vision-improving. The Vitex trifolia fruit mentioned above... vines Using dried, ripe fruit, the thorny nut (Fructus tribulus) is known for its ability to "disperse wind-heat and clear the head and eyes." tribulus The dried, ripe fruit is used for its properties of "soothing the liver and relieving depression, dispelling wind and improving eyesight." Together, these two ingredients work synergistically to enhance the "wind-relieving and dizziness-suppressing" power of the principal ingredient, dizziness, headache, blurred vision, and other head and facial symptoms. The auxiliary ingredients, through "treating phlegm" and "clearing wind," enhance the therapeutic intensity and scope of the principal ingredient from different pathways.

[0023] Lysamide, patchouli, acorus tatarinowii, bitter orange blossom, litsea cubeba, galangal, and frangipani are used as adjuvant herbs for comprehensive treatment, addressing concurrent symptoms. Patchouli, litsea cubeba, and galangal are used as adjuvant herbs to resolve dampness and harmonize the stomach; all three herbs have aromatic properties and are warm and drying in nature. In this invention, the patchouli... Pogostemon cablin (Blanco) Benth. uses its dried aerial parts, "aromatically transforming turbidity," as described in the Litsea cubeba. Litsea euosma WW Smith, L. soft Hemsl. or L. pungens Hemsl. uses its dried fruit, which is said to "warm the middle and promote qi circulation," as mentioned in the text. Kaempferia galangaLinn. uses dried rhizomes to "warm the middle and dispel dampness." The combined effect of these three ingredients targets the fundamental pathogenesis of "dampness obstructing the middle jiao," powerfully removing dampness and turbidity, restoring spleen and stomach function, and fundamentally eliminating nausea. The aforementioned Acorus tatarinowii... Acorus tatarinowii Schott et al. use dried rhizomes as an adjuvant for opening the orifices and calming the mind. This product is a key medicine for opening the orifices, capable of "resolving dampness and invigorating the stomach, opening the orifices and resolving phlegm, and refreshing the mind and improving intelligence." It can both help resolve dampness and phlegm, thus awakening the senses and relieving mental drowsiness and confusion, similar to the sedative effect of lisdexampleminamine. Bitter orange blossom and frangipani are adjuvants for regulating qi and relieving chest tightness. The aforementioned bitter orange blossom... Citrus aurantium L. var. bitter Engl. uses dried flower buds, which are said to "regulate qi, relieve chest tightness, stimulate appetite, and stop vomiting." Its pleasant aroma is effective in treating chest tightness and discomfort. The frangipani flower described... Red plumeria L. cv. Sharp-leaved The dried flowers are used; they "clear heat and promote diuresis," and are slightly cooling in nature. This helps to counteract the excessive warming properties of the other herbs in the formula, preventing them from generating heat and thus making the formula more balanced. Together, they alleviate symptoms of motion sickness such as chest tightness and irritability caused by qi stagnation. The large and clearly defined team of supporting herbs reflects the comprehensive nature of this formula.

[0024] Menthol acts as an adjuvant, guiding the other herbs to the appropriate meridians and harmonizing their effects. It guides the herbs upwards: Menthol is light and ascending, with a strong and refreshing aroma, capable of "dispersing wind-heat and clearing the head and eyes"; it acts like a guide, directing the power of the other herbs in the formula to the head and face, allowing the medicinal effects to reach the affected area directly. It enhances efficacy and provides comfort: its cooling sensation can immediately relieve dizziness and headaches, providing significant comfort. It harmonizes the properties of the other herbs: its cooling nature can slightly counteract the warming and drying effects of the entire formula, achieving a harmonizing effect.

[0025] This invention relates to a compound composition for the prevention and treatment of motion sickness, with each component acting as a principal, assistant, adjuvant, and guiding herb in a tightly linked manner. The principal herb addresses the acute symptoms (dizziness, vomiting, drowsiness); the assistant herbs assist in their effects (resolving phlegm, clearing wind); the adjuvant herbs provide overall protection (resolving dampness, opening the orifices, regulating qi); and the guiding herb directs the effects (ascending to the head and eyes). This formula integrates the precise target control of modern pharmacology (such as H1 receptor antagonism and central nervous system excitation) with the holistic regulation and comprehensive treatment of both the symptoms and root cause in Traditional Chinese Medicine. It covers multiple aspects, from the vestibular center (diphenhydramine, acorus tatarinowii, tribulus terrestris), the vomiting center (ginger), the gastrointestinal tract (tangerine peel, patchouli, litsea cubeba), to mental and emotional states (lysexadefenamide, bitter orange blossom), and subjective feelings (menthol), forming a three-dimensional treatment network that integrates Chinese and Western medicine and covers all target areas.

[0026] The core of this invention lies in deeply integrating the targets of modern chemical drugs with traditional Chinese medicine theories to form an organic whole. Chemical drugs are considered "units" with specific medicinal properties of traditional Chinese medicine, integrated into the entire prescription system. This invention strictly follows the core pathogenesis of motion sickness in traditional Chinese medicine—"wind movement, phlegm obstruction, dampness accumulation, and qi reversal"—emphasizing comprehensive coverage of motion sickness symptoms. It not only targets the core symptoms of motion sickness, such as nausea and vomiting, but also provides precise intervention for complex accompanying symptoms such as headache, tinnitus, lethargy, chest tightness, and a sticky feeling in the mouth, offering more comprehensive symptom relief and a better patient experience.

[0027] A second aspect of the present invention provides a method for preparing the compound composition for preventing and treating motion sickness according to the above description, comprising the following steps: (1) The following herbs were extracted with water: ginger, tangerine peel, vitex fruit, tribulus fruit, acorus tatarinowii, patchouli, bitter orange flower, litsea cubeba, galangal, and frangipani. The extract was filtered, the filtrate was concentrated, and dried to obtain the herbal extract. (2) The Chinese herbal extract obtained in step (1) is mixed with dimenhydrinate, lysdexample, and a pharmaceutically acceptable carrier or excipient to obtain a mixture; (3) Dissolve menthol in anhydrous ethanol and add it to the mixed powder in step (2) in the mixed state by spraying. Continue mixing to allow the ethanol to evaporate and dry to obtain the compound composition for the prevention and treatment of motion sickness.

[0028] In some embodiments of the present invention, the water extraction step in step (1) includes: adding the Chinese medicine ingredients to 8 to 12 times the amount of water for decoction, for example, 8, 9, 10, 11 or 12 times the amount of water, decoct 2 to 3 times, each time for 1 to 2 hours, for example 1 hour, 1.5 hours or 2 hours.

[0029] In some embodiments of the present invention, the mesh size of the filter cloth used for filtration in step (1) is 150-250 mesh. For example, it is 150-180 mesh, 180-200 mesh, 200-230 mesh, or 230-250 mesh.

[0030] In some embodiments of the present invention, the drying temperature in step (1) is 50~60°C. For example, it is 50~52°C, 52~54°C, 54~56°C, 56~58°C or 58~60°C.

[0031] In some embodiments of the present invention, the concentration in step (1) is to concentrate to a relative density of 1.2 to 1.3. For example, it is 1.2 to 1.22, 1.22 to 1.24, 1.24 to 1.25, 1.25 to 1.26, 1.26 to 1.28, or 1.28 to 1.3.

[0032] In some embodiments of the present invention, the concentration conditions in step (1) are 65~80°C and -0.06~-0.1 MPa. For example, the temperature is 65~70°C, 70~75°C, or 75~80°C. For example, the pressure is -0.06~-0.07 MPa, -0.07~-0.08 MPa, -0.08~-0.09 MPa, or -0.09~-0.1 MPa.

[0033] In some embodiments of the present invention, the amount of anhydrous ethanol in step (3) is 1.5 to 2.5 times that of menthol. For example, it is 1.5 to 1.7 times, 1.7 to 2.0 times, 2.0 to 2.3 times, or 2.3 to 2.5 times.

[0034] In some embodiments of the present invention, the mixing time in step (3) is 10 to 20 minutes. For example, it is 10 to 13 minutes, 13 to 15 minutes, 15 to 17 minutes, or 17 to 20 minutes.

[0035] In this invention, "pharmaceutical acceptable" means that when properly administered to animals or humans in conjunction with the formulation ingredients, they do not produce adverse, allergic, or other adverse reactions.

[0036] "Pharmaceutically acceptable carriers or excipients" should be compatible with the formulation components, meaning they can be mixed with them without significantly reducing the efficacy of the drug composition under normal circumstances. Specific examples of substances that can serve as pharmaceutically acceptable carriers or excipients include: sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium methylcellulose, ethylcellulose, methylcellulose, and microcrystalline cellulose; tragacanth gum powder; malt; gelatin; talc; solid lubricants such as stearic acid and magnesium stearate; calcium sulfate; vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil, and cocoa butter; polyols such as propylene glycol, glycerin, sorbitol, mannitol, and polyethylene glycol; alginic acid; emulsifiers such as Tween; wetting agents such as sodium lauryl sulfate; colorants; flavoring agents; tableting agents; stabilizers; disintegrants; antioxidants; preservatives; pyrogen-free water; isotonic salt solutions; and phosphate buffers. These substances are used as needed to help stabilize the formulation or to improve its activity or bioavailability or to produce an acceptable taste or smell when taken orally.

[0037] A third aspect of the present invention provides a medicament for preparing a drug for preventing and / or treating motion sickness, based on the use of the above-described compound composition.

[0038] Example 1 Preparation of a compound for the prevention and treatment of motion sickness: prescription: Dimenhydrinate 3 parts, lysine dextromethorphan 0.3 parts, ginger 22 parts, dried tangerine peel 15 parts, Vitex trifolia 12 parts, Tribulus terrestris 12 parts, Acorus tatarinowii 10 parts, patchouli 12 parts, bitter orange blossom 8 parts, Litsea cubeba 5 parts, Kaempferia galanga 5 parts, frangipani 8 parts, menthol 2 parts, microcrystalline cellulose 40 parts, crospovidone 10 parts, magnesium stearate 2 parts.

[0039] Preparation method: (1) Pretreatment of the Chinese herbal medicine: Weigh the prescribed amounts of ginger, tangerine peel, vitex fruit, tribulus terrestris, acorus tatarinowii, patchouli, bitter orange blossom, litsea cubeba, galangal, and frangipani. Soak in 10 times the amount of water for 1 hour, and extract twice by reflux, 1.5 hours each time. Combine the two extracts and filter with a 200-mesh filter cloth. Concentrate the filtrate under reduced pressure at 70°C and -0.08MPa to a thick paste with a relative density of 1.30 (60°C). Mix the Chinese herbal medicine paste with 30 parts of microcrystalline cellulose, dry under reduced pressure at 60°C and -0.08MPa until the moisture content is ≤5.0%, and pulverize through a 100-mesh sieve to obtain "Chinese herbal medicine extract powder".

[0040] (2) Final mixing: Place the "Chinese herbal extract powder" with dimenhydrinate, lysd-phenylpropanol, the remaining 10 parts of microcrystalline cellulose, and crospovidone (disintegrant) in a three-dimensional motion mixer and mix for 30 minutes until fully homogeneous. Dissolve menthol in 2 times its volume of anhydrous ethanol and add it to the above mixed powder in a spray form, mixing for 15 minutes to allow the ethanol to evaporate. Finally, add magnesium stearate and mix for another 5 minutes.

[0041] (3) Filling: The mixed final powder is filled into No. 0 empty capsules using a fully automatic capsule filling machine to obtain the compound capsule of the present invention.

[0042] Comparative Example 1 Chemical tablets: prescription: 3 parts of dimenhydrinate, 0.3 parts of lysadecanol (calculated as free base), 6 parts of starch, 2 parts of microcrystalline cellulose, and 0.15 parts of magnesium stearate.

[0043] Preparation method: (1) Mixing: Dimenhydrinate, lysine, starch and microcrystalline cellulose are passed through an 80-mesh sieve and mixed thoroughly in a mixer using an equal-increment method.

[0044] (2) Granulation: Add an appropriate amount of purified water to the well-mixed powder as a binder to make soft material, and granulate it with a 16-mesh sieve.

[0045] (3) Drying and granulation: Dry the wet granules at 60°C until the moisture content is <3.0%, and then granulate them through a 16-mesh sieve.

[0046] (4) Total mixing and tableting: Mix the dry granules with magnesium stearate evenly and compress them into tablets using a tableting machine.

[0047] Comparative Example 2 Traditional Chinese medicine compound granules: prescription: 22 parts ginger; 15 parts dried tangerine peel; 12 parts Vitex trifolia; 12 parts Tribulus terrestris; 10 parts Acorus tatarinowii; 12 parts Pogostemon cablin; 8 parts Citrus aurantium; 5 parts Litsea cubeba; 5 parts Kaempferia galanga; 8 parts Frangipani; 2 parts menthol; 30 parts dextrin.

[0048] Preparation method: (1) Extraction: Weigh the prescribed amounts of ginger, tangerine peel, vitex fruit, tribulus terrestris, acorus tatarinowii, patchouli, bitter orange flower, litsea cubeba, galangal, and frangipani. Soak in 10 times the amount of water for 1 hour, and extract twice by reflux, each time for 1.5 hours. Combine the two extracts and filter with a 200-mesh filter cloth.

[0049] (2) Concentration: The filtrate is concentrated under reduced pressure at 70°C and -0.08MPa to a thick paste with a relative density of 1.30 (60°C).

[0050] (3) Granulation: Mix the thick paste with dextrin to prepare a soft material, and granulate it using a 14-mesh sieve.

[0051] (4) Drying and mixing: Dry the wet granules at 60°C until the moisture content is <5.0%. Mix the dried granules with menthol (which can be dissolved in a small amount of ethanol and then sprayed in), granulate, and package to obtain Chinese medicine granules.

[0052] Comparative Example 3 Commercially available dimenhydrinate tablets.

[0053] Pharmaceutical Experiment Experimental animals: Male SD rats, weighing 210-240g. Motion sickness sensitivity was screened before the formal experiment; rats that ingested less than 1g of kaolin after rotational stimulation were excluded. Male Beagle dogs, weighing 7-11kg.

[0054] Rotational stimulation model: The parameters of the rotational stimulation device are set according to a cycle of clockwise acceleration and deceleration, followed by counterclockwise acceleration and deceleration. The acceleration time is 7.5 seconds, and the acceleration is 16° / s². 2 The deceleration time is 2.5 seconds, and the acceleration during deceleration is -48° / s². 2 Rotation amplitude 700°, duration 10s; each cycle 20s. Rats were continuously stimulated for 45min. Beagles were stimulated until vomiting occurred; the times of salivation and vomiting were recorded.

[0055] 1. Consumption amount of kaolin Principle: Nausea and vomiting are the most prominent symptoms of motion sickness. Rats, being rodents, lack a vomiting reflex. When experiencing motion sickness, rats exhibit pica, i.e., consuming non-nutritive substances (such as bedding). The rat pica model is the most commonly used animal model for studying motion sickness. This highly corresponds to the nausea and vomiting in human motion sickness (rats cannot vomit). The more severe the motion sickness, the greater the kaolin ingestion. This indicator has high specificity and a very good correlation with the severity of motion sickness, making it an internationally recognized core indicator.

[0056] Kaolin preparation: Mix 1000g of kaolin and 20g of gum arabic powder in equal increments, add 400ml of distilled water, stir into a paste, press into a feed-like consistency using a disposable syringe, and air dry at room temperature.

[0057] Observation Methods: Forty-eight rats were randomly divided into six groups: control group, model group, comparative group 1 (chemical drug, 5.8 mg / kg (amount of dimenhydrinate + lysdexampleamine / body weight)), comparative group 2 (traditional Chinese medicine compound, 11.1 g / kg (raw drug amount / body weight)), comparative group 3 (dimenhydrinate 5.2 mg / kg), and example group 1 (compound of this invention 11.4 g / kg (raw drug amount / body weight)), with eight rats in each group. For the capsule dosage form, the contents were prepared as a suspension using a 0.5% sodium carboxymethyl cellulose aqueous solution; for the tablet and granule dosage forms, the contents were ground into a fine powder and then prepared as a suspension using a 0.5% sodium carboxymethyl cellulose aqueous solution. The raw drug amount refers to the amount of the prescription raw materials, and the dosage was calculated according to the human dosage. Rats were housed individually in metabolic cages with free access to food and water. A certain amount of feed and kaolin were provided daily at regular intervals, kept separate, and rats insensitive to the stimulation were culled before the formal rotational stimulation test. Thirty minutes before rotational stimulation, rats were administered the corresponding drugs by gavage, while rats in the control and model groups were administered physiological saline by gavage. After rotational stimulation, the amount of kaolin consumed was recorded for three consecutive days, accurately weighed to the nearest 0.01g. See Table 1 for details.

[0058] Table 1. Kaolin consumption in rats 3 days after rotational stimulation (n=8) Note: Compared with the control group, aa P<0.01; compared with the model group, b P<0.05, bb P<0.01; compared with Comparative Example 1 (chemical drug), c P<0.05, cc P<0.01; compared with the control group 2 (traditional Chinese medicine compound), dd P<0.01; compared with comparative example group 3 (dimenhydrinate), ee P<0.01.

[0059] As shown in Table 1, compared with the control group, the amount of kaolin consumed by rats in the model group was significantly increased (P<0.01), indicating that the rotational stimulation model was successfully established. Compared with the model group, the amount of kaolin consumed by rats in Comparative Example 1 (chemical drug) (P<0.01), Comparative Example 2 (traditional Chinese medicine compound) (P<0.05), Comparative Example 3 (tea-dimenhydrinate) (P<0.01), and Example 1 (P<0.01) was significantly decreased, indicating that each drug group could significantly inhibit the motion sickness response induced by rotational stimulation in rats. Compared with the three comparative groups, the amount of kaolin consumed by rats in Example 1 with the compound of the present invention was significantly reduced (P<0.05 or P<0.01), and was close to that of the control group, indicating that the anti-motion sickness effect of the compound of the present invention in Example 1 was the best, followed by Comparative Example 1 (chemical drug) and Comparative Example 3 (tea-dimenhydrinate).

[0060] 2. Gastric emptying rate Principle: Motion sickness is accompanied by a strong inhibition of gastric emptying, leading to delayed gastric emptying. Effective relief of gastric emptying response can serve as an auxiliary indicator for evaluating motion sickness medications. By euthanizing animals after rotational stimulation and measuring the weight of gastric residue (e.g., measuring absorbance after gavage with phenol red solution), the regulatory effect of drugs on gastrointestinal dysfunction caused by motion sickness can be directly verified.

[0061] Observation Methods: 48 rats were grouped and administered drugs at the same concentrations as before. 30 minutes before the rotational stimulation, each rat was administered the corresponding drug concentration by gavage. 30 minutes later, each rat was administered 0.5 ml / gavage of a 1.5% CMC-Na solution containing 0.1% phenol red. Immediately after the rotational stimulation was applied for 45 minutes (operation as before), the rats were euthanized by cervical dislocation. The abdominal cavity was opened, the pylorus and cardia were ligated, the entire stomach was removed, and cut along the greater curvature. The stomach contents were rinsed with physiological saline, and the volume was adjusted to 20 ml. Then, 20 ml of 0.5 mol / L NaOH solution was added, and the mixture was shaken repeatedly and allowed to stand for 1 hour. 5 ml of the supernatant was collected, and 0.5 ml of trichloroacetic acid solution (20%) was added to remove protein. The mixture was centrifuged at 3000 r / min for 10 minutes, and the absorbance of the supernatant was measured at 560 nm. Eight more rats were administered 0.5 ml / rat of a 1.5% CMC-Na solution containing 0.1% phenol red via gavage. They were immediately euthanized, and absorbance values ​​were measured using the method described above. The mean value was calculated as the standard value (i.e., zero gastric emptying). Gastric emptying rate (%) = (1 - OD of experimental group) 560 / Standard OD 560 () × 100%. The results are shown in Table 2.

[0062] Table 2. Gastric emptying rate in rats after rotational stimulation (n=8) Note: Compared with the control group, aa P<0.01; compared with the model group, b P<0.05, bbP<0.01; compared with Comparative Example 1 (chemical drug), c P<0.01; compared with comparative example group 3 (dimenhydrinate), dd P<0.01.

[0063] As shown in Table 2, compared with the control group, the gastric emptying rate of rats in the model group was significantly reduced (P<0.01), indicating that the rotational stimulation model was successfully established. Compared with the model group, the gastric emptying rates of rats in Comparative Example 1 (P<0.05), Comparative Example 2 (P<0.01), Comparative Example 3 (P<0.01), and Example 1 (P<0.01) were all significantly increased, indicating that each drug group could significantly inhibit the decrease in gastric emptying in rats with motion sickness induced by rotational stimulation. Compared with Comparative Example 1 (chemical drug) and Comparative Example 3 (dimenhydrinate), the gastric emptying rate of rats in Example 1 was significantly increased (P<0.01) and close to that of the control group, indicating that the compound of the present invention in Example 1 was more effective than Comparative Example 1 (chemical drug) and Comparative Example 3 (dimenhydrinate) in inhibiting the effect of motion sickness on the gastric emptying rate of rats.

[0064] 3. Incubation period for drooling and vomiting Twenty Beagle dogs were randomly divided into five groups: a model group, a control group 1 (chemical drug, 1.7 mg / kg (dimenhydrinate + lysdexample) / body weight), a control group 2 (traditional Chinese medicine compound, 3.3 g / kg (crude drug / body weight)), a control group 3 (dimenhydrinate 1.6 mg / kg), and an example group 1 (the compound of this invention 3.4 g / kg (crude drug / body weight)), with four dogs in each group. For the capsule formulation, the contents were prepared as a suspension using a 0.5% sodium carboxymethyl cellulose aqueous solution; for the tablet and granule formulations, the contents were ground into a fine powder and then prepared as a suspension using a 0.5% sodium carboxymethyl cellulose aqueous solution. The crude drug amount refers to the amount of the prescribed raw materials, and the dosage was calculated according to the human dosage. One hour after each dog was administered the corresponding drug by gavage (the model group was administered physiological saline), rotational stimulation was initiated, and the time of salivation and vomiting was recorded. If no salivation or vomiting occurs after 30 minutes of rotation, stop the experiment and record the latency period for salivation or vomiting as 30 minutes. See Table 3.

[0065] Table 3. Latency period of salivation and vomiting in dogs after rotational stimulation (n=4) Note: Compared with the model group, aa P<0.01, a P<0.05; compared with Comparative Example 1 (chemical drug), b P<0.05; compared with control group 2 (traditional Chinese medicine compound), c P<0.05, cc P<0.01; compared with comparative example group 3 (dimenhydrinate), dP<0.05.

[0066] Table 3 shows that compared with the model group, the latency periods for salivation and vomiting in Comparative Example 1 (P<0.01, P<0.01), Comparative Example 2 (P<0.01, P<0.05), Comparative Example 3 (P<0.01, P<0.01), and Example 1 (P<0.01, P<0.01) were significantly prolonged, indicating that each drug group could significantly inhibit motion sickness induced by rotational stimulation in dogs. Compared with the three comparative groups, the latency periods for salivation and vomiting in Example 1, using the compound of the present invention, were significantly prolonged (P<0.05 or P<0.01, exception: the latency period for salivation was not statistically significant compared with Comparative Example 3 (dimenhydrinate), but showed a clear upward trend), indicating that the compound of the present invention had the best anti-motion sickness effect, followed by Comparative Example 1 (chemical drug) and Comparative Example 3 (dimenhydrinate). This result is consistent with the results of the kaolin consumption in rats mentioned above.

[0067] 4. Side effect evaluation Principle: An open field test was used to evaluate the effect of each drug group on the spontaneous activity level of rats with motion sickness, in order to evaluate the effect of the drugs on the drowsiness of rats with motion sickness.

[0068] Observation method: 48 rats were grouped and administered drugs at the same concentrations as before. 30 minutes before the rotational stimulation, the rats were administered the corresponding concentration of drug by gavage. After 45 minutes of rotational stimulation (operation as before), spontaneous activity was observed.

[0069] Spontaneous Activity Monitoring: Rats were quickly placed in a fully enclosed spontaneous activity box with black walls. The system automatically tracked the animal's movement using infrared light, recording and calculating the movement trajectory and parameters in real time. Finally, analysis software was used to analyze the rats' exploratory activities over 3 minutes. The total distance traveled and the number of spontaneous activities were analyzed. The results are shown in Table 4.

[0070] Table 4 Spontaneous activity of rats after rotational stimulation (n=8) Note: Compared with the control group, aa P<0.01; compared with the model group, bb P<0.01; compared with Comparative Example 1 (chemical drug), c P<0.05, cc P<0.01; compared with the control group 2 (traditional Chinese medicine compound), dd P<0.01; compared with comparative example group 3 (dimenhydrinate), ee P<0.01.

[0071] As shown in Table 4, compared with the control group, the total distance traveled (P<0.01) and number of spontaneous movements (P<0.01) of the model group rats were significantly reduced, indicating that the rotational stimulation model was successfully established. Compared with the model group rats, the total distance traveled and number of spontaneous movements were significantly increased in Comparative Example 1 (P<0.01, P<0.01), Comparative Example 2 (P<0.01, P<0.01), and Example 1 (P<0.01, P<0.01), indicating that the chemical drugs, traditional Chinese medicine compound, and whole formula in the present invention can significantly inhibit motion sickness induced by rotational stimulation. The spontaneous activity of rats decreased; compared with Comparative Example 1 (chemical drug), the total distance (P<0.01) and number of spontaneous activities (P<0.05) of rats in Comparative Example 2 (traditional Chinese medicine compound) were significantly reduced, suggesting that the chemical drug was more effective than the traditional Chinese medicine compound in inhibiting the decrease in spontaneous activity in rats with motion sickness. The total distance (P<0.01) and number of spontaneous activities (P<0.01) of rats in Example 1 were significantly higher than those in Comparative Example 2 (traditional Chinese medicine compound), and close to those in Comparative Example 1 (chemical drug) and the control group, suggesting that the compound of the present invention has the best effect in inhibiting the decrease in spontaneous activity in rats caused by motion sickness.

[0072] The above experimental results show that the compound of the present invention in Example 1 is significantly superior to Comparative Example 1 (chemical drug) and Comparative Example 2 (traditional Chinese medicine compound) in significantly reducing the amount of kaolin ingested by rats with motion sickness and prolonging the latency period of salivation and vomiting in dogs with motion sickness, demonstrating the synergistic effect of the combined use of chemical drugs and traditional Chinese medicine. Regarding gastric emptying, the compound of the present invention in Example 1 has a better protective effect on gastric emptying than Comparative Example 1 (chemical drug) and Comparative Example 3 (dimenhydrinate). Meanwhile, the spontaneous activity level of rats in Example 1 is not significantly different from that in the control group, indicating that it successfully eliminated the drowsy side effect of dimenhydrinate, demonstrating the significant advantages of the composition of the present invention in terms of efficacy and safety.

[0073] In summary, the compound composition of the present invention combines the potency and rapid effect of Comparative Example 1 (chemical drug) with the comprehensiveness and gentleness of Comparative Example 2 (traditional Chinese medicine compound). That is, the compound composition of the present invention can quickly control dizziness and vomiting, while utilizing the sedative and heat-clearing properties of traditional Chinese medicine (such as Acorus tatarinowii and Plumeria rubra) to effectively buffer the tension that lysex may cause and the drowsiness of dimenhydrinate, achieving the goal of "high efficiency and comfort" synergistic effect and toxicity reduction.

[0074] Therefore, this invention effectively overcomes the various shortcomings of the prior art and has high industrial application value.

[0075] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A compound composition for the prevention and treatment of motion sickness, characterized in that, By weight, it includes the following ingredients: Dimenhydrinate 2-6 parts, lysine dextromethorphan 0.2-0.6 parts, ginger 20-50 parts, dried tangerine peel 10-20 parts, Vitex trifolia 8-15 parts, Tribulus terrestris 8-15 parts, Acorus tatarinowii 5-12 parts, patchouli 8-15 parts, bitter orange blossom 5-10 parts, Litsea cubeba 3-8 parts, Kaempferia galanga 3-8 parts, frangipani 5-10 parts, menthol 0.5-3 parts.

2. The compound composition according to claim 1, characterized in that, By weight, it includes the following ingredients: Dimenhydrinate 3-5 parts, lysine dextromethorphan 0.3-0.5 parts, ginger 22-30 parts, dried tangerine peel 14-18 parts, Vitex trifolia 10-13 parts, Tribulus terrestris 10-13 parts, Acorus tatarinowii 8-10 parts, patchouli 10-13 parts, bitter orange blossom 6-8 parts, Litsea cubeba 4-6 parts, Kaempferia galanga 4-6 parts, frangipani 6-8 parts, menthol 1-2 parts.

3. The compound composition according to claim 1, characterized in that, By weight, it includes the following ingredients: Dimenhydrinate 3 parts, lysine dextromethorphan 0.4 parts, ginger 22 parts, dried tangerine peel 15 parts, Vitex trifolia 12 parts, Tribulus terrestris 12 parts, Acorus tatarinowii 10 parts, patchouli 12 parts, bitter orange flower 8 parts, Litsea cubeba 5 parts, Kaempferia galanga 5 parts, frangipani 8 parts, menthol 2 parts.

4. A method for preparing a compound composition for preventing and treating motion sickness according to any one of claims 1 to 3, characterized in that, Includes the following steps: (1) The following herbs were extracted with water: ginger, tangerine peel, vitex fruit, tribulus fruit, acorus tatarinowii, patchouli, bitter orange flower, litsea cubeba, galangal, and frangipani. The extract was filtered, the filtrate was concentrated, and dried to obtain the herbal extract. (2) The Chinese herbal extract obtained in step (1) is mixed with dimenhydrinate, lysdexample, and a pharmaceutically acceptable carrier or excipient to obtain a mixture; (3) Dissolve menthol in anhydrous ethanol and add it to the mixed powder in step (2) in the mixed state by spraying. Continue mixing to allow the ethanol to evaporate and dry to obtain the compound composition for the prevention and treatment of motion sickness.

5. The preparation method according to claim 4, characterized in that, The water extraction step described in step (1) includes: adding the Chinese herbal ingredients to 8 to 12 times the amount of water for decoction, decoct 2 to 3 times, 1 to 2 hours each time.

6. The preparation method according to claim 4, characterized in that, It also includes one or more of the following features: A1) The mesh size of the filter cloth used for filtration in step (1) is 150~250 mesh; A2) The drying temperature described in step (1) is 50~60°C; A3) The concentration mentioned in step (1) is to concentrate to a relative density of 1.2~1.3; A4) The concentration conditions described in step (1) are 65~80°C and -0.06~-0.1Mpa.

7. The preparation method according to claim 4, characterized in that, It also includes one or more of the following features: B1) The amount of anhydrous ethanol mentioned in step (3) is 1.5 to 2.5 times that of menthol; B2) The mixing time described in step (3) is 10-20 minutes.

8. The preparation method according to claim 4, characterized in that, The compound composition is suitable for preparation into an oral dosage form.

9. The preparation method according to claim 8, characterized in that, The oral dosage form is selected from tablets, capsules, granules, oral liquids, or orally disintegrating tablets.

10. Use of a compound composition according to any one of claims 1 to 3, characterized in that, Used to prepare drugs for the prevention and / or treatment of motion sickness.

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