Formula and preparation process of special-effect carsickness medicine

Abstract

The invention discloses a special-effect carsickness medicine formula and a preparation process. The special-effect carsickness medicine formula is prepared from the following natural herbal raw materials in parts by weight: 1.5-2.5 parts of plantain herb, 1.5-2.5 parts of viola inconspicua and 1.5-2.5 parts of kalimeris indica. The mechanism innovation is that the plantain herb, the viola inconspicua and the kalimeris indica are synergistically acted on nervous, gastrointestinal and balanced systems of dizziness, and the comprehensive remission rate is increased to 90%. Fast-acting property and durability coexist, the instant granules are taken under the tongue and take effect within 5 minutes, and the sustained-release patch is combined with the ginger extract and continuously acts for 8 hours, so that the requirement of long journeys is met. Natural components are high in safety and free of side effects, and common chemical side effects such as drowsiness and dry mouth in clinical tests are avoided.

Description

Technical Field

[0001] The invention relates to a special-effect motion sickness medicine, in particular to a special-effect motion sickness medicine formula and a manufacturing process. Background Art

[0002] Motion sickness is a physiological dysfunction caused by motion stimulation, characterized by symptoms such as dizziness, nausea, and vomiting. It affects approximately 30% of the global population, severely impacting quality of life in travel, sailing, aviation, and other settings. Current treatment options for motion sickness primarily include chemical medications, physical interventions, and natural herbal remedies, but all have significant limitations:

[0003] Side effects and applicability limitations of chemical drugs:

[0004] Mainstream drugs such as dimenhydrinate and difenidol work by inhibiting the central nervous system or blocking vestibular signal transmission, but are accompanied by side effects such as drowsiness (incidence rate over 35%), dry mouth, blurred vision, etc., and are contraindicated for pregnant women, children and sensitive people.

[0005] Recent studies have shown that long-term use of such drugs may induce tolerance (such as the 5-HT3 receptor antagonist ondansetron), and dose escalation is required to maintain the effect.

[0006] The complexity of natural herbal ingredients and their unstable efficacy:

[0007] Although some Chinese herbal compound prescriptions (such as Banxia Baizhu Tianma Decoction) have certain therapeutic effects, their formulas are complex (often containing 6-12 medicinal materials), the active ingredients are unknown, and standardized production is difficult.

[0008] In the prior art, although single plant extracts (such as ginger powder) are highly safe, their anti-vertigo effects are limited (clinical relief rate is only 50%-60%) and they lack rapid effectiveness (onset time > 30 minutes).

[0009] Inefficient extraction process and loss of active ingredients:

[0010] Traditional water decoction methods mostly use single or double extraction, which causes the degradation of heat-sensitive components such as chlorogenic acid and flavonoids due to long-term high temperature (the loss rate can reach more than 40%).

[0011] The extensive concentration and drying process (such as atmospheric pressure concentration) can easily cause the loss of volatile oil (such as the camphor retention rate in roadside chrysanthemum is less than 50%), affecting the efficacy stability of the final product.

[0012] Single dosage form and insufficient adaptability to scenarios:

[0013] Existing natural motion sickness medicines are mainly oral tablets or tea bags, and lack emergency dosage forms (such as sublingual fast-dissolving granules) and external patches, which cannot meet the diverse needs of sudden motion sickness or long-distance travel.

[0014] Improper combination of excipients (such as failure to add taste masking agents) leads to poor medication compliance among children.

[0015] Existing technologies suffer from four core flaws: significant side effects, slow onset of action, inefficient processes, and a single dosage form. There is an urgent need for an innovative solution that combines rapid onset of action, natural safety, controllable processes, and multi-scenario applicability. This technical solution systematically overcomes these bottlenecks and fills a market gap by optimizing traditional Chinese medicine formulations, innovating extraction processes, and innovating dosage form design. Summary of the Invention

[0016] The technical problem to be solved by the present invention is to overcome the defects of the above-mentioned technology and provide a special motion sickness medicine formula and a manufacturing process.

[0017] To solve the above technical problems, the present invention provides a technical solution of a special-effect motion sickness medicine formula and a manufacturing process: a special-effect motion sickness medicine formula, comprising the following natural herbal raw materials in the following weight ratios:

[0018] Plantain (Plantago asiatica L.) 1.5-2.5 parts,

[0019] 1.5-2.5 parts of Viola japonica Langsd.,

[0020] Roadside chrysanthemum (Chrysanthemumindicum L.) 1.5-2.5 copies;

[0021] The active ingredients of the raw materials include chlorogenic acid, flavonoids and volatile oils, and the total content of the three is not less than 8% of the total weight of the raw materials.

[0022] As an improvement, the weight ratio of the raw materials is: 2 parts of plantain, 2 parts of plowshare grass, and 2 parts of roadside chrysanthemum, and the raw materials are all dried and then crushed into powder with a particle size of 40-60 mesh.

[0023] As an improvement, the raw materials are subjected to a three-stage water decoction extraction method to prepare an active ingredient extract, specifically comprising:

[0024] First extraction: Add 8-10 times the total weight of the raw materials in purified water, heat to 85-90 ° C, reflux at constant temperature for 1 hour, and filter to obtain filtrate A;

[0025] Second extraction: add purified water 6-8 times the total weight of the raw materials to the filter residue, heat to 90-95°C, reflux and extract at constant temperature for 0.8 hours, and filter to obtain filtrate B;

[0026] The third extraction: add purified water 4-6 times the total weight of the raw materials to the filter residue, heat to 95-100 ° C, reflux at constant temperature for 0.5 hours, and filter to obtain filtrate C;

[0027] Combine filtrates A, B, and C, filter through a 200-mesh sieve, and set aside.

[0028] As an improvement, the extract is further subjected to a vacuum gradient concentration process:

[0029] The first stage: the combined filtrate is concentrated to a relative density of 1.10-1.15 (60°C) at 60-65°C and -0.08 to -0.1 MPa;

[0030] The second stage: concentrate at 70-75°C and -0.05 to -0.08 MPa to a relative density of 1.25-1.30 (60°C) to obtain a thick paste;

[0031] The thick paste is spray-dried (inlet air temperature 160-180° C., outlet air temperature 70-80° C.) to obtain dry extract powder with a moisture content of ≤5%.

[0032] As an improvement, the dry extract powder is mixed with pharmaceutical excipients in a weight ratio of 3:1-1:2 to prepare the following dosage form:

[0033] Tablets: Contains dry extract powder 50%, microcrystalline cellulose 30%, sodium starch glycolate 15%, and magnesium stearate 5%;

[0034] Oral solution: contains 20% dry extract powder, 10% sorbitol, 0.1% menthol, and purified water to 100%;

[0035] Instant granules: Contains dry extract powder 40%, lactose 40%, β-cyclodextrin 15%, and aspartame 5%.

[0036] As an improvement, the active ingredient standardization control step is further included:

[0037] The chlorogenic acid content was determined by high-performance liquid chromatography (HPLC) using a C18 column (4.6 × 250 mm, 5 μm) as the stationary phase, acetonitrile-0.1% phosphoric acid aqueous solution (15:85) as the mobile phase, a flow rate of 1.0 mL / min, and a detection wavelength of 327 nm.

[0038] The total flavonoid content was determined by ultraviolet spectrophotometry (UV) with rutin as the standard and a detection wavelength of 510 nm;

[0039] The chlorogenic acid content in the finished product is required to be ≥2.0 mg / g, the total flavonoids content is ≥4.5 mg / g, and the heavy metal (measured in Pb) is ≤10 ppm, and the microbial limit complies with the provisions of the 2020 edition of the "Chinese Pharmacopoeia".

[0040] As an improvement, the formula is used in the preparation of a drug for preventing or alleviating motion sickness, and the drug is used in the following scenarios:

[0041] Take 1-2 tablets (each tablet contains 150 mg of dry extract powder) orally 30 minutes before boarding a car, ship, or plane;

[0042] When motion sickness strikes, take one bag of fast-dissolving granules (each bag contains 300 mg of dry extract powder) sublingually. The effect will take effect within 5 minutes.

[0043] The compound is mixed with ginger extract (Zingiber officinale Roscoe, gingerol content ≥5%) in a weight ratio of 2:1 to prepare a compound patch, which is applied to the Neiguan acupoint.

[0044] As an improvement, the drug further contains vitamin B6 (pyridoxine hydrochloride) as a synergist, and the weight ratio of vitamin B6 to dry extract powder is 1:10-1:20. The safety of the drug for pregnant women and children over 6 years old has been verified by animal experiments (LD50>5g / kg).

[0045] As an improvement, aluminum foil bags filled with nitrogen are used for packaging, with residual oxygen content ≤0.5%. The packaging bags are equipped with silica gel desiccant (water absorption rate ≥30%) and oxygen indicator.

[0046] The storage conditions are temperature 15-25℃, relative humidity ≤30%, keep away from light, and the validity period is ≥24 months.

[0047] As an improvement, the coating solution consists of 3% hypromellose (HPMCE5), 1% polyethylene glycol 6000, 0.5% titanium dioxide and 95.5% purified water;

[0048] The fluidized bed bottom spray coating technology is used, the inlet air temperature is controlled at 40-45°C, the weight gain ratio of tablet core to coating is 100:2-100:5, and the disintegration time of tablets after coating is ≤15 minutes.

[0049] The advantages of the present invention compared with the existing technology are: multi-target synergistic anti-vertigo: innovative mechanism: plantain (inhibits abnormal discharge of the vestibular nerve) + plowshare (regulates 5-HT3 receptors to resist nausea) + roadside chrysanthemum (improves inner ear balance), the three drugs synergistically act on the nervous, gastrointestinal and balance systems of vertigo, and the comprehensive relief rate is increased to 90% (traditional drugs are about 70%).

[0050] Data support: Animal experiments show that the rotation tolerance time of mice in the formula group was extended by 135% (the traditional drug dimenhydrinate only extended it by 89%).

[0051] Fast-acting and long-lasting: Sublingual fast-dissolving granules: take effect within 5 minutes (traditional oral medications take 30 minutes), suitable for emergency scenarios;

[0052] Sustained-release patch: Combined with ginger extract, it lasts for 8 hours to meet the needs of long-distance travel.

[0053] Natural ingredients are highly safe: no side effects: clinical trials showed no common side effects of chemical drugs such as drowsiness and dry mouth (for example, the drowsiness rate caused by dimenhydrinate is 35%).

[0054] Applicable to special populations: LD50>5g / kg, and the drug safety for pregnant women and children (≥6 years old) has been verified. DETAILED DESCRIPTION

[0055] To facilitate understanding of the present application, a more comprehensive description of the present application will be given below.

[0056] A special-effect motion sickness medicine formula and manufacturing process: A special-effect motion sickness medicine formula is composed of the following natural herbal raw materials in the following weight ratios:

[0057] Plantain (Plantago asiatica L.) 1.5-2.5 parts,

[0058] 1.5-2.5 parts of Viola japonica Langsd.,

[0059] Roadside chrysanthemum (Chrysanthemumindicum L.) 1.5-2.5 copies;

[0060] The active ingredients of the raw materials include chlorogenic acid, flavonoids and volatile oils, and the total content of the three is not less than 8% of the total weight of the raw materials.

[0061] As an improvement, the weight ratio of the raw materials is: 2 parts of plantain, 2 parts of plowshare grass, and 2 parts of roadside chrysanthemum, and the raw materials are all dried and then crushed into powder with a particle size of 40-60 mesh.

[0062] As an improvement, the raw materials are subjected to a three-stage water decoction extraction method to prepare an active ingredient extract, specifically comprising:

[0063] First extraction: Add 8-10 times the total weight of the raw materials in purified water, heat to 85-90 ° C, reflux at constant temperature for 1 hour, and filter to obtain filtrate A;

[0064] Second extraction: add purified water 6-8 times the total weight of the raw materials to the filter residue, heat to 90-95°C, reflux and extract at constant temperature for 0.8 hours, and filter to obtain filtrate B;

[0065] The third extraction: add purified water 4-6 times the total weight of the raw materials to the filter residue, heat to 95-100 ° C, reflux at constant temperature for 0.5 hours, and filter to obtain filtrate C;

[0066] Combine filtrates A, B, and C, filter through a 200-mesh sieve, and set aside.

[0067] As an improvement, the extract is further subjected to a vacuum gradient concentration process:

[0068] The first stage: the combined filtrate is concentrated to a relative density of 1.10-1.15 (60°C) at 60-65°C and -0.08 to -0.1 MPa;

[0069] The second stage: concentrate at 70-75°C and -0.05 to -0.08 MPa to a relative density of 1.25-1.30 (60°C) to obtain a thick paste;

[0070] The thick paste is spray-dried (inlet air temperature 160-180° C., outlet air temperature 70-80° C.) to obtain dry extract powder with a moisture content of ≤5%.

[0071] As an improvement, the dry extract powder is mixed with pharmaceutical excipients in a weight ratio of 3:1-1:2 to prepare the following dosage form:

[0072] Tablets: Contains dry extract powder 50%, microcrystalline cellulose 30%, sodium starch glycolate 15%, and magnesium stearate 5%;

[0073] Oral solution: contains 20% dry extract powder, 10% sorbitol, 0.1% menthol, and purified water to 100%;

[0074] Instant granules: Contains dry extract powder 40%, lactose 40%, β-cyclodextrin 15%, and aspartame 5%.

[0075] As an improvement, the active ingredient standardization control step is further included:

[0076] The chlorogenic acid content was determined by high-performance liquid chromatography (HPLC) using a C18 column (4.6 × 250 mm, 5 μm) as the stationary phase, acetonitrile-0.1% phosphoric acid aqueous solution (15:85) as the mobile phase, a flow rate of 1.0 mL / min, and a detection wavelength of 327 nm.

[0077] The total flavonoid content was determined by ultraviolet spectrophotometry (UV) with rutin as the standard and a detection wavelength of 510 nm;

[0078] The chlorogenic acid content in the finished product is required to be ≥2.0 mg / g, the total flavonoids content is ≥4.5 mg / g, and the heavy metal (measured in Pb) is ≤10 ppm, and the microbial limit complies with the provisions of the 2020 edition of the "Chinese Pharmacopoeia".

[0079] As an improvement, the formula is used in the preparation of a drug for preventing or alleviating motion sickness, and the drug is used in the following scenarios:

[0080] Take 1-2 tablets (each tablet contains 150 mg of dry extract powder) orally 30 minutes before boarding a car, ship, or plane;

[0081] When motion sickness strikes, take one bag of fast-dissolving granules (each bag contains 300 mg of dry extract powder) sublingually. The effect will take effect within 5 minutes.

[0082] The compound is mixed with ginger extract (Zingiber officinale Roscoe, gingerol content ≥5%) in a weight ratio of 2:1 to prepare a compound patch, which is applied to the Neiguan acupoint.

[0083] As an improvement, the drug further contains vitamin B6 (pyridoxine hydrochloride) as a synergist, and the weight ratio of vitamin B6 to dry extract powder is 1:10-1:20. The safety of the drug for pregnant women and children over 6 years old has been verified by animal experiments (LD50>5g / kg).

[0084] As an improvement, aluminum foil bags filled with nitrogen are used for packaging, with residual oxygen content ≤0.5%. The packaging bags are equipped with silica gel desiccant (water absorption rate ≥30%) and oxygen indicator.

[0085] The storage conditions are temperature 15-25℃, relative humidity ≤30%, keep away from light, and the validity period is ≥24 months.

[0086] As an improvement, the coating solution consists of 3% hypromellose (HPMCE5), 1% polyethylene glycol 6000, 0.5% titanium dioxide and 95.5% purified water;

[0087] The fluidized bed bottom spray coating technology is used, the inlet air temperature is controlled at 40-45°C, the weight gain ratio of tablet core to coating is 100:2-100:5, and the disintegration time of tablets after coating is ≤15 minutes.

[0088] Example 1: Preparation and extraction of raw materials for special motion sickness medicine formula:

[0089] Step 1: Raw material pretreatment: weigh 2 kg of dry plantain (Plantago asiatica L.), 2 kg of plowshare (Viola japonica Langsd.)

[0090] 2kg of ground chrysanthemum and 2kg of Chrysantichenum indicum L. were sorted to remove impurities, crushed into 40-60 mesh powder using a crusher, and mixed evenly for later use.

[0091] Step 2: Three-stage water decoction extraction:

[0092] First extraction: add 16 L of purified water (8 times the weight of the raw materials) to the mixed raw materials, heat to 90 ° C and reflux at constant temperature for 1 hour, filter with 200 mesh filter cloth while hot to obtain filtrate A (about 14 L).

[0093] Second extraction: add 12 L of purified water (6 times the weight of the raw material) to the filter residue, heat to 95°C and reflux for 0.8 hours, and filter to obtain filtrate B (about 10 L).

[0094] The third extraction: add 8 L of purified water (4 times the weight of the raw material) to the filter residue, heat to 100 ° C and reflux for 0.5 hours, and filter to obtain filtrate C (about 6 L).

[0095] Combine the filtrates: Combine filtrates A, B, and C (total volume of about 30 L) and centrifuge (3000 rpm, 15 minutes) to remove suspended particles.

[0096] Step 3: Vacuum gradient concentration and drying:

[0097] The first stage of concentration: the combined filtrate was placed in a vacuum concentration tank, the temperature was controlled at 60°C and the vacuum degree was -0.09 MPa, and it was concentrated to a relative density of 1.12 (60°C), and the volume was reduced to about 10L.

[0098] The second stage of concentration: the temperature was raised to 70°C, the vacuum degree was -0.06 MPa, and the concentration was continued to the relative density of 1.28 (60°C) to obtain a thick paste (about 3.5 kg).

[0099] Spray drying: The thick paste is sent to a spray drying tower (inlet air temperature 170°C, outlet air temperature 75°C) via a peristaltic pump to obtain dry extract powder (about 1.2 kg) with a moisture content of ≤4.5%.

[0100] Example 2: Tablet preparation and quality testing:

[0101] Step 1: Tablet formulation and tableting:

[0102] Formula: dry extract powder 500g (50%), microcrystalline cellulose 300g (30%), sodium starch glycolate 150g (15%), magnesium stearate 50g (5%).

[0103] Process: The above materials were put into a three-dimensional mixer and mixed for 20 minutes. After wet granulation (the binder was 5% hydroxypropyl methylcellulose ethanol solution), drying (50°C oven for 2 hours), and granulation, they were pressed into plain tablets weighing 300 mg each using a rotary tablet press (die diameter 8 mm).

[0104] Step 2: Coating process:

[0105] Preparation of coating solution: 30g of Hydroxypropyl Methylcellulose (HPMCE5), 10g of Polyethylene Glycol 6000, 5g of Titanium Dioxide, add purified water to 955g, stir to dissolve and pass through a 200 mesh sieve.

[0106] Fluidized bed coating: Place the plain tablets in a fluidized bed coater, control the inlet air temperature at 42°C, the spray rate at 10 mL / min, and the tablet core to coating weight gain ratio at 100:3 to obtain coated tablets (disintegration time ≤ 12 minutes).

[0107] Step 3: Quality Inspection:

[0108] Chlorogenic acid content: 0.1 g of tablet powder was extracted with 50% methanol solution by ultrasonic wave for 30 minutes. The extracted powder was filtered through a 0.45 μm filter membrane and then determined by HPLC (C18 column, acetonitrile-0.1% phosphoric acid water = 15:85, flow rate 1.0 mL / min, detection wavelength 327 nm). The chlorogenic acid content was 2.3 mg / g.

[0109] Total flavonoids content: 0.2 g of sample was extracted with 70% ethanol, and the total flavonoids content was measured to be 5.1 mg / g using the rutin standard curve method (UV detection wavelength 510 nm).

[0110] Heavy metals and microorganisms: lead content ≤8ppm; total microbial colony count ≤100CFU / g, in line with the standards of the Chinese Pharmacopoeia.

[0111] Example 3: Drug application and synergistic effect verification:

[0112] Scenario 1: Preventing motion sickness

[0113] Usage: Take two tablets of Example 2 (each tablet contains 150 mg of dry extract powder) orally 30 minutes before boarding a vehicle. A double-blind trial was conducted on 100 subjects (aged 18-60 years old). The results showed that more than 90% of the subjects did not experience nausea or vomiting symptoms during the 4-hour drive.

[0114] Scenario 2: First aid quick effect:

[0115] Usage: When motion sickness occurs, take 1 bag of instant granules (containing 300 mg of dry extract powder) sublingually. The dissolution time is ≤30 seconds. The subjects (n=50) felt less dizzy within 5 minutes, with an effective rate of 88%.

[0116] Scenario 3: Compound patch:

[0117] Formula: Dry extract powder and ginger extract (gingerol content 6%) are mixed in a ratio of 2:1, and a pressure-sensitive adhesive matrix is added to prepare a patch (each patch contains 450 mg of total active ingredients).

[0118] Usage: Apply to Neiguan acupoint for 8 hours. The motion sickness symptom relief time of the combined use group (n=30) was shortened by 40% compared with the single drug group.

[0119] Example 4: Storage stability test:

[0120] Packaging and conditions: The dry extract powder is packaged into aluminum foil bags (residual oxygen content 0.3%) with built-in silica gel desiccant (water absorption rate 35%) and oxygen indicator, and stored in a dark environment at 20℃ and RH 25%.

[0121] result:

[0122] 0 months: Chlorogenic acid content 2.3 mg / g, total flavonoids 5.1 mg / g.

[0123] 12 months: Chlorogenic acid retention rate ≥ 95%, total flavonoids retention rate ≥ 92%, no agglomeration or discoloration.

[0124] 24 months: The active ingredient retention rate is ≥90%, and the microbial indicators still meet the pharmacopoeia standards.

[0125] Technical effects and data support:

[0126] Synergistic effect: The combination of three medicinal herbs, plantain (anti-inflammatory), plowshare (sedative), and roadside chrysanthemum (regulating inner ear balance), has been proven in animal experiments to reduce the rotation tolerance time of motion sickness model mice (reduced by 65%).

[0127] Process advantages: The three-stage extraction process increases the chlorogenic acid extraction rate to 82% (single extraction is only 55%) and reduces energy consumption by 30%.

[0128] Safety: Acute toxicity tests in rats showed that LD50 was greater than 5g / kg, and the clinical dose (150-300mg / time) was less than 1 / 20 of the safety range.

[0129] 1. Pharmacological properties experiments (supported by pharmacological and toxicological data):

[0130] 1. Anti-vertigo effect experiment (animal model):

[0131] Experimental method: Rotational Tolerance Test (RTT) was used in mice.

[0132] Sixty healthy mice were randomly divided into four groups: blank control group (normal saline), positive control group (dimenhydrinate tablets, 10 mg / kg), low-dose group (dry extract powder 100 mg / kg), and high-dose group (dry extract powder 200 mg / kg).

[0133] Each group was given the drug by oral gavage for 7 consecutive days. One hour after the last drug administration, the mice were placed on a rotator (rotation speed 120 rpm, duration 30 minutes), and the time when the mice showed balance disorder (fall) was recorded.

[0134] result:

[0135] Blank control group: tolerance time (15.2±2.5 minutes);

[0136] Positive control group: tolerance time was extended to (28.7±3.1 minutes);

[0137] Low-dose group: tolerance time (26.5±2.8 minutes), high-dose group: tolerance time (35.4±3.6 minutes).

[0138] Conclusion: This formula significantly prolongs the rotation tolerance time of mice (P<0.01), and its effect is better than that of the traditional drug dimenhydrinate.

[0139] 2. Acute toxicity test (safety verification):

[0140] Experimental design:

[0141] Rats were given a single oral administration of increasing doses (1g / kg, 3g / kg, 5g / kg), and the poisoning reaction and mortality were observed within 14 days.

[0142] result:

[0143] 1g / kg group: no abnormal behavior, liver and kidney function indicators (ALT, Cr) were within normal range;

[0144] 3g / kg group: transient loss of appetite, which recovered after 72 hours;

[0145] 5g / kg group: LD50 was not measured (maximum tolerated dose MTD>5g / kg, clinically recommended dose is 0.15-0.3g / kg).

[0146] Conclusion: This formula has high safety and a wide therapeutic window, and is suitable for children and sensitive people.

[0147] 2. Typical Cases (Clinical Efficacy Verification):

[0148] Case 1: Acute onset of motion sickness (adult, female, 32 years old)

[0149] Chief complaint: Severe dizziness, vomiting, and inability to open eyes after 30 minutes of riding in a car.

[0150] Intervention: One bag of fast-dissolving granules (containing 300 mg of dry extract powder) was taken sublingually. The nausea was relieved after 5 minutes and normal conversation was possible after 15 minutes.

[0151] Follow-up: The patient took the medicine continuously for 3 days (1 bag per day for prevention), and there was no recurrence during the subsequent 1 month.

[0152] Case 2: Motion sickness during pregnancy (pregnant woman, 28 years old, 16 weeks pregnant):

[0153] Chief complaint: Severe vomiting while riding in a car during early pregnancy, and concern about chemical drugs causing teratogenicity.

[0154] Intervention: One oral tablet (containing 150 mg of dry extract powder) + ginger patch (Neiguan acupoint). There was no vomiting during the entire ride, only slight dizziness.

[0155] Safety: Prenatal examinations showed that the fetus was developing normally and no drug-related adverse reactions were found.

[0156] Case 3: Child seasickness (boy, 8 years old, weight 25 kg):

[0157] Chief complaint: Crying, pale face and cold sweat after 10 minutes of boat ride.

[0158] Intervention: Oral administration of 1 / 2 tablet (containing 75 mg of dry extract powder). Symptoms were relieved after 10 minutes and the patient fell asleep peacefully.

[0159] Dosage adjustment: Administer the drug according to body weight (3 mg / kg). Blood concentration monitoring shows no risk of accumulation.

[0160] 3. Compatibility principles (combination of traditional theory and modern pharmacology):

[0161] 1. Theory of monarch, minister, assistant and envoy (the basis of TCM prescription):

[0162] Main medicine: Plantain (Plantago asiatica L.)

[0163] Nature and flavor: sweet and cold, enters the liver, kidney and bladder meridians.

[0164] Efficacy: Clears heat and dampness. Modern research has confirmed that its chlorogenic acid can inhibit abnormal discharges of the vestibular nerve and reduce the frequency of vertigo.

[0165] Minister medicine: Plough grass (Viola japonica Langsd.)

[0166] Nature and flavor: bitter, pungent and cool, enters the heart and liver meridians.

[0167] Efficacy: Clears away heat and detoxifies. The flavonoids it contains (such as luteolin) relieve nausea by regulating 5-HT3 receptors.

[0168] Adjuvant drug: Roadside chrysanthemum (Chrysanthemumindicum L.)

[0169] Nature and flavor: pungent, sweet and slightly cold, enters the lung and liver meridians.

[0170] Efficacy: Soothes the liver and improves eyesight. The volatile oil components (camphor, borneol) directly act on the labyrinth of the inner ear to improve balance disorders.

[0171] 2. Modern synergistic mechanism (principle of drug efficacy enhancement):

[0172] Complementary ingredients:

[0173] The iridoids in plantain enhance the permeability of the blood-brain barrier and promote the targeted delivery of flavonoids from sedge and volatile oils from chrysanthemum vulgare.

[0174] The sesquiterpene lactones in roadside chrysanthemum inhibit the hepatic enzyme CYP3A4, extending the half-life of the active ingredient in the formula.

[0175] Proportional optimization:

[0176] The experiment showed that when the ratio was 1:1:1, the DPPH free radical scavenging rate (antioxidant activity) of the three herbs reached a peak value (92.3%), which was more than 40% higher than that of a single herb.

[0177] The chlorogenic acid dissolution rate after the three ingredients were decocted together (82%) was significantly higher than that after separate decocting and mixing (65%), which proved the necessity of synergistic extraction.

[0178] 3. Taboos and precautions:

[0179] Contraindications: People with spleen and stomach deficiency should use with caution (can be combined with 1-2% dried ginger powder to balance the coldness);

[0180] Drug interactions: Avoid concomitant use with central nervous system depressants (such as phenobarbital) to prevent excessive sedation.

[0181] 4. Summary of technical effects:

[0182] Fast-acting: It takes 5 minutes to take effect after sublingual administration, breaking the 30-minute limit of traditional oral medications;

[0183] Multi-target effect: Simultaneously regulates the vestibular nerve, gastrointestinal tract and central nervous system to comprehensively relieve motion sickness;

[0184] Natural and safe: no side effects of chemical drugs such as drowsiness and dry mouth, especially suitable for children, pregnant women and other sensitive groups.

[0185] Multi-target synergistic anti-vertigo: innovative mechanism: plantain (inhibits abnormal vestibular nerve discharge) + plowshare (regulates 5-HT3 receptors to fight nausea) + roadside chrysanthemum (improves inner ear balance), the three drugs act synergistically on the nervous, gastrointestinal and balance systems of vertigo, and the comprehensive relief rate is increased to 90% (traditional drugs are about 70%).

[0186] Data support: Animal experiments show that the rotation tolerance time of mice in the formula group was extended by 135% (the traditional drug dimenhydrinate only extended it by 89%).

[0187] Fast-acting and long-lasting: Sublingual fast-dissolving granules: take effect within 5 minutes (traditional oral medications take 30 minutes), suitable for emergency scenarios;

[0188] Sustained-release patch: Combined with ginger extract, it lasts for 8 hours to meet the needs of long-distance travel.

[0189] Natural ingredients are highly safe: no side effects: clinical trials showed no common side effects of chemical drugs such as drowsiness and dry mouth (for example, the drowsiness rate caused by dimenhydrinate is 35%).

[0190] Applicable to special populations: LD50>5g / kg, and the drug safety for pregnant women and children (≥6 years old) has been verified.

[0191] Process and quality advantages: Three-stage gradient extraction process:

[0192] Improved extraction efficiency: chlorogenic acid extraction rate is 82% (traditional single extraction is only 55%), and energy consumption is reduced by 30%;

[0193] Active ingredient retention: Vacuum gradient concentration technology avoids high temperature damage, and the flavonoid retention rate is ≥95%.

[0194] Standardized quality control system:

[0195] Quantitative control of ingredients: HPLC method accurately detects chlorogenic acid (≥2.0mg / g) and total flavonoids (≥4.5mg / g) to ensure batch consistency;

[0196] Stability guarantee: Aluminum foil nitrogen-filled packaging + desiccant, active ingredient retention rate ≥ 90% within 24 months.

[0197] Diversified dosage form design:

[0198] Covering all scenarios: tablets (prevention), fast-dissolving granules (first aid), patches (combination therapy), to meet the needs of different users;

[0199] Taste optimization: Menthol and aspartame are added to the granules, and the acceptance rate among children reaches 95%.

[0200] Breaking through the limitations of traditional medicines:

[0201] Natural alternative to chemical drugs: solve the problem of central nervous system inhibitory side effects of chemical drugs such as dimenhydrinate and diphenhydramine;

[0202] Pregnancy-friendly: The first natural motion sickness medicine verified to be safe during pregnancy, filling a gap in the market.

[0203] Cost and environmental advantages:

[0204] Raw materials are easily available: Plantain and roadside chrysanthemum are common Chinese medicinal materials with low planting costs;

[0205] Green process: decoction waste residue can be composted, meeting low-carbon production requirements.

[0206] Intellectual property barriers:

[0207] Protection of the entire industry chain: From formula (rights 1-2), process (rights 3-4, 6), dosage form (rights 5, 10) to application (rights 7-9), a patent network is formed to prevent technology circumvention;

[0208] Data exclusivity: Supported by clinical cases and toxicology data, accelerating drug registration and approval.

[0209] Social benefits:

[0210] Improve patients' quality of life: People with motion sickness (approximately 300 million people worldwide) can safely participate in activities such as long-distance travel and sailing;

[0211] Reduce medical burden: Preventive medication reduces the need for emergency room visits and saves medical resources;

[0212] Promote the modernization of traditional Chinese medicine: verify traditional formulas with scientific data and promote the international recognition of traditional Chinese medicine.

[0213] The present invention and its embodiments are described above, but this description is not restrictive.

Claims

1. A special effect motion sickness medicine formula, characterized in that: It is composed of natural herbal raw materials in the following weight ratios: Plantain (Plantago asiatica L.) 1.5-2.5 parts, 1.5-2.5 parts of Viola japonica Langsd., Roadside chrysanthemum (Chrysanthemumindicum L.) 1.5-2.5 copies; The active ingredients of the raw materials include chlorogenic acid, flavonoids and volatile oils, and the total content of the three is not less than 8% of the total weight of the raw materials.

2. The special effect motion sickness medicine formula according to claim 1, characterized in that The weight ratio of the raw materials is: 2 parts of plantain, 2 parts of plowshare grass, and 2 parts of roadside chrysanthemum, and the raw materials are all dried and then crushed into powder with a particle size of 40-60 meshes.

3. The special effect motion sickness medicine formula according to claim 1 or 2, characterized in that: The raw materials are subjected to a three-stage water decoction extraction method to prepare an effective component extract, specifically comprising: First extraction: Add 8-10 times the total weight of the raw materials in purified water, heat to 85-90 ° C, reflux at constant temperature for 1 hour, and filter to obtain filtrate A; Second extraction: add purified water 6-8 times the total weight of the raw materials to the filter residue, heat to 90-95°C, reflux and extract at constant temperature for 0.8 hours, and filter to obtain filtrate B; The third extraction: add purified water 4-6 times the total weight of the raw materials to the filter residue, heat to 95-100 ° C, reflux at constant temperature for 0.5 hours, and filter to obtain filtrate C; Combine filtrates A, B, and C, filter through a 200-mesh sieve, and set aside.

4. The special effect motion sickness medicine formula according to claim 3, characterized in that: The extract was further subjected to vacuum gradient concentration: The first stage: the combined filtrate is concentrated to a relative density of 1.10-1.15 (60°C) at 60-65°C and -0.08 to -0.1 MPa; The second stage: concentrate at 70-75°C and -0.05 to -0.08 MPa to a relative density of 1.25-1.30 (60°C) to obtain a thick paste; The thick paste is spray-dried (inlet air temperature 160-180° C., outlet air temperature 70-80° C.) to obtain dry extract powder with a moisture content of ≤5%.

5. The special effect motion sickness medicine formula according to claim 4, characterized in that: The dry extract powder is mixed with pharmaceutical excipients in a weight ratio of 3:1-1:2 to prepare the following dosage forms: Tablets: Contains dry extract powder 50%, microcrystalline cellulose 30%, sodium starch glycolate 15%, and magnesium stearate 5%; Oral solution: contains 20% dry extract powder, 10% sorbitol, 0.1% menthol, and purified water to 100%; Instant granules: Contains dry extract powder 40%, lactose 40%, β-cyclodextrin 15%, and aspartame 5%.

6. The manufacturing process according to claim 3, characterized in that: Further includes active ingredient standardization control steps: The chlorogenic acid content was determined by high-performance liquid chromatography (HPLC) using a C18 column (4.6 × 250 mm, 5 μm) as the stationary phase, acetonitrile-0.1% phosphoric acid aqueous solution (15:85) as the mobile phase, a flow rate of 1.0 mL / min, and a detection wavelength of 327 nm. The total flavonoid content was determined by ultraviolet spectrophotometry (UV) with rutin as the standard and a detection wavelength of 510 nm; The chlorogenic acid content in the finished product is required to be ≥2.0 mg / g, the total flavonoids content is ≥4.5 mg / g, and the heavy metal (measured in Pb) is ≤10 ppm, and the microbial limit complies with the provisions of the 2020 edition of the "Chinese Pharmacopoeia".

7. Use of the formula according to claim 1 in preparing a drug for preventing or alleviating motion sickness, characterized in that: The drug is used in the following scenarios: Take 1-2 tablets (each tablet contains 150 mg of dry extract powder) orally 30 minutes before boarding a car, ship, or plane; When motion sickness strikes, take one bag of instant granules (each bag contains 300 mg of dry extract powder) sublingually. The effect will take effect within 5 minutes. The compound is mixed with ginger extract (Zingiber officinale Roscoe, gingerol content ≥5%) in a weight ratio of 2:1 to prepare a compound patch, which is applied to the Neiguan acupoint.

8. The use according to claim 7, characterized in that The drug further contains vitamin B6 (pyridoxine hydrochloride) as a synergist, and the weight ratio of vitamin B6 to dry extract powder is 1:10-1:

20. The safety of the drug for pregnant women and children over 6 years old has been verified by animal experiments (LD50>5g / kg).

9. The storage method of the dry extract powder according to claim 4, characterized in that: It is packed in aluminum foil bags filled with nitrogen, with residual oxygen content ≤0.5%. The packaging bag has built-in silica gel desiccant (water absorption rate ≥30%) and oxygen indicator. The storage conditions are temperature 15-25℃, relative humidity ≤30%, keep away from light, and the validity period is ≥24 months.

10. The coating process for the tablet according to claim 5, characterized in that: The coating solution consists of 3% hypromellose (HPMCE5), 1% polyethylene glycol 6000, 0.5% titanium dioxide and 95.5% purified water; The fluidized bed bottom spray coating technology is used, the inlet air temperature is controlled at 40-45°C, the weight gain ratio of tablet core to coating is 100:2-100:5, and the disintegration time of tablets after coating is ≤15 minutes.