External traditional Chinese medicine composition for treating migraine as well as preparation method and application of external traditional Chinese medicine composition

Abstract

The invention discloses an external traditional Chinese medicine composition for treating migraine. The composition is a medicament prepared from the following raw material medicines in parts by weight: 16-30 parts of fresh radish root, 8-15 parts of fresh ginger, 1-3 parts of fresh mint leaf and 0.3-2 parts of clove powder. The pharmaceutical composition is a pure traditional Chinese medicine preparation, aims at the basic pathogenesis that wind-cold is mainly used and orifice clearing is unfavorable when headache attacks, and achieves the purpose of rapidly relieving pain by purging evil to dredge orifices and promoting qi circulation. In the formula, the four medicines of radish root, clove, ginger and mint are adopted, and through the application of a fresh medicine preparation and aromatic resuscitation-inducing medicines and the compatibility of medicines with pungent and warm medicines as main medicines and medicines with pungent and cool medicines as assistant and guide medicines, the aromatic and pungent effects of the medicines can be furthest taken, so that the effects of inducing resuscitation and relieving pain are achieved. Meanwhile, the four medicines in the pharmaceutical composition are all medicinal and edible traditional Chinese medicines, all have application experience of ancient doctors for nasal administration, and the pharmaceutical composition has relatively good safety while being low in price.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to an external Chinese medicine composition for treating migraine, a preparation method and application thereof. Background Art

[0002] Migraine is a widespread neurological disease with high morbidity, high disability rate and early onset age, which brings heavy burden to individuals and social economy. Compared with traditional oral medications, topical medications such as nasal administration can better meet the rapid analgesic needs of migraine patients in the acute phase. Nasal administration has become the main research direction for the treatment of acute migraine due to its advantages such as rapid onset, high bioavailability and few side effects. At present, topical preparations for migraine mainly include injections, transdermal patches, suppositories and nasal administration.

[0003] Injections are injected directly into the vein, muscle or subcutaneously, and the drug is absorbed into the blood to achieve the therapeutic effect directly, bypassing the digestive tract absorption and first-pass metabolism of the liver, and rapidly increasing the plasma and brain concentrations of the drug. However, it may also cause some patients to experience worse nausea and vomiting, or lead to other concentration-dependent adverse events. At the same time, intravenous injection is an operation that requires professional skills, which increases the difficulty of self-treatment for patients. This may also be one of the reasons why the latest developed injections are all adjusted to subcutaneous injections.

[0004] Transdermal patches are a type of dosage form that delivers drugs through skin absorption to achieve therapeutic purposes. In the 2020 edition of the Pharmacopoeia of the People's Republic of China, under the item "Patches", transdermal patches are defined as patches that are applied to the intact skin surface and can deliver drugs through the skin into the blood circulation system to exert systemic effects [1]. The drug currently on the market is the triptan drug Zelrix (sumatriptan) [2]. At the same time, fentanyl transdermal patches and buprenorphine transdermal patches are opioid drugs. Although they have good analgesic effects, they are not recommended as first-line drugs for migraine. Transdermal administration is a non-invasive form of administration that has the advantages of avoiding the first-pass effect of the liver, avoiding gastrointestinal metabolism, prolonging the effective duration of action, and stabilizing blood drug concentrations. Patches are easy to use and can be used independently by patients. However, patches also face the technical challenge of difficult transdermal absorption of drugs with poor skin permeability, such as poorly soluble drugs, peptide protein macromolecular drugs, and hydrophilic drugs [3]. At the same time, as a topical drug, the melting point of the drug, the adhesion of the patch, and the research and development of transdermal agents all increase the difficulty of transdermal agent development. Skin irritation and the improvement of efficacy are both problems currently faced.

[0005] Suppositories are a more traditional dosage form that is widely used in various medical fields. Suppositories of antipyretic analgesics such as indomethacin and antiemetics such as domperidone can avoid the problem of patients being unable to take oral medications due to nausea and vomiting. Suppositories of ergotamine drugs are better absorbed, but necrotizing ergotism can occur, often causing spasms of arteries throughout the body. The above 3 drugs are not first-line medications for migraine. Since the drugs are absorbed through the rectal mucosa and enter the blood and brain relatively slowly, suppositories are rarely used for the specific treatment of migraine.

[0006] Among them, nasal administration mainly applies drugs to the nasal cavity through nasal sprays and nasal powder aerosols, and is absorbed through the respiratory mucosa, olfactory mucosa and respiratory tract. Compared with other drug administration methods, the advantages of nasal administration [4-6] include: drugs can be absorbed through the nasal mucosa to bypass the blood-brain barrier and directly transported into the olfactory bulb or cerebrospinal fluid, avoiding the problem of low oral bioavailability of drugs; the blood vessels under the nasal mucosa are abundant, which is easy to absorb drugs and avoids the first-pass effect; the administration method is convenient, which can increase patients' medication compliance; it can also increase the transport of drugs into the brain, thereby achieving the purpose of targeted treatment, etc.

[0007] At present, the economic burden of migraine treatment drugs is still very huge, mainly reflected in the high cost of specific analgesics and new drugs. In a US study on the cost of lamivudine in the treatment of migraine attacks [7], the annual cost of commonly used drugs for migraine attacks was calculated and compared. It was found that the cost of zolmitriptan nasal spray was as high as US$1456.92 / year, US$80.94 / time, and the cost of sumatriptan nasal spray was as high as US$799.29 / year, US$49.96 / time, which caused a huge economic burden. New migraine treatment drugs are basically first launched in Europe and the United States. There are very limited channels for purchasing in my country, and medical insurance coverage is relatively small, resulting in limited clinical use and low popularity in my country.

[0008] Research on Chinese herbal nasal preparations often has problems such as low research quality and low quality of evidence for clinical effectiveness and safety evaluation. Only through clinical efficacy observation or clinical research with a small sample size, and the design of efficacy indicators does not meet the requirements of international efficacy evaluation, and the classification of suitable populations is unclear, resulting in low efficacy recognition and application popularity of Chinese herbal nasal preparations.

[0009] Currently, some drugs have been introduced in the form of nasal administration, such as zavirigepam, sumatriptan, zolmitriptan, dihydroergotamine mesylate, flunarizine, etc.

[0010] However, these drugs are relatively expensive, such as zolmitriptan nasal spray costs up to $1,456.92 per year and sumatriptan nasal spray costs up to $799.29 per year. At the same time, medical insurance does not cover all of these drugs, which to some extent increases the financial pressure of using these drugs.

[0011] In my country, there are also some studies on nasal administration. For example, a study used a self-made meridian syndrome differentiation method to treat headaches, and the results showed that its efficacy was comparable to that of ibuprofen capsules.

[0012] In addition, there are studies using Sitongsan nasal plugs and Tubisan, etc., which showed significant improvements in the number of people whose headaches disappeared and the severity of their headaches after treatment.

[0013] However, existing nasal drug formulations mainly focus on the combined use of drugs such as Chuanxiong and Asarum.

[0014] Therefore, the present invention selects Chinese medicinal materials that are both medicinal and edible, such as radish root, clove, ginger, mint, etc. as drug ingredients by consulting ancient Chinese medical books and modern research, in order to improve the diversity and coverage of drug treatment on the basis of ensuring safety, thereby bringing hope to more headache patients. Summary of the invention

[0015] To achieve the above purpose, the present invention provides a Chinese medicine composition for external use for treating migraine, a preparation method and application thereof, and the technical scheme adopted is: the technical scheme of the present invention is based on the understanding and treatment principles of the pathogenesis of migraine in traditional Chinese medicine, with reference to the achievements of modern pharmacological research, and adopts the mode of nasal administration, aiming at the basic pathogenesis of headache mainly caused by wind-cold and poor clearing of the orifices, and achieves the purpose of treating migraine through the effects of purging evil, opening the orifices, and promoting the flow of qi.

[0016] The invention discloses a medicament prepared from raw materials in the following weight proportion: 16-30 parts of fresh radish roots, 8-15 parts of ginger, 1-3 parts of fresh mint leaves and 0.3-2 parts of clove powder.

[0017] The preferred weight ratio is: 24 parts of fresh radish roots, 12 parts of ginger, 2 parts of fresh mint leaves, and 1 part of clove powder.

[0018] The preparation method of the medicine of the present invention is as follows:

[0019] Weigh the raw Chinese medicinal materials according to the above amounts;

[0020] Mix and mash the above-mentioned fresh radish roots, ginger and fresh mint leaves, and filter to obtain juice;

[0021] Pass clove powder through a 100-mesh sieve and add it to the medicine juice in step ②;

[0022] Mix thoroughly and filter using filter paper;

[0023] The filtrate is diluted with distilled water to a pH in the range of 5.5-6.5 [1].

[0024] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0025] The technical scheme of the present invention is based on the recognition and treatment principle of the pathogenesis of migraine in traditional Chinese medicine, with reference to the achievements of modern pharmacological research, and adopts the mode of nasal administration, for the basic pathogenesis of wind-cold as the main and clear orifices unfavorable during headache attack, through the effects of purging evil and opening the orifices, and promoting the function of qi, the purpose of treating migraine is achieved. The present invention is based on the records of ancient Chinese medical books and modern research prescriptions, and the Chinese medicine radish root, cloves, ginger, and mint, which are both medicinal and edible, are selected as prescription compositions. While ensuring safety, there are clinical practice records of traditional Chinese medical theory support and ancient doctors' single or compatibility applications, but there is no related research on the composition, which is innovative, can improve the difference of external medicines for headache, and cover a wider range of headache population. The pharmaceutical composition of the present invention is a pure Chinese medicine preparation, for the basic pathogenesis of wind-cold as the main and clear orifices unfavorable during headache attack, purging evil and opening the orifices, and promoting the function of qi to achieve the purpose of rapid analgesia. The prescription adopts radish root, clove, ginger and mint, and attaches importance to the application of aromatic drugs for opening the mind through fresh drug preparation. The combination of pungent and warm drugs as the main ingredients and pungent and cool drugs as the auxiliary ingredients can maximize the aromatic and pungent effects to achieve the function of opening the mind and relieving pain. At the same time, the four drugs in the pharmaceutical composition of the present invention are all Chinese medicines with the same origin as medicine and food, and all have the application experience of ancient doctors in nasal administration. While the price is low, the preparation process is simple, easy to operate at home, and has good safety. DETAILED DESCRIPTION

[0026] The following description is used to disclose the present invention so that those skilled in the art can implement the present invention. The preferred embodiments described below are only examples, and those skilled in the art may think of other obvious variations. Example 1

[0027] 1. Weigh the following amounts of raw materials: 240 g fresh radish root, 120 g ginger, 20 g fresh mint leaves, and 10 g clove powder.

[0028] 2. Mix and mash the above-mentioned fresh radish roots, ginger and fresh mint leaves, and filter to obtain the juice;

[0029] 3. Pass the clove powder through a 100-mesh sieve and add it to the medicine juice in step 2;

[0030] 4. Mix thoroughly and filter with filter paper;

[0031] 5. Use distilled water to dilute the filtrate until the pH is within the range of 5.5-6.5. Example 2

[0032] After the preparation of the drug, before use, the pH value of the drug (each sample was tested 3 times) and the sedimentation volume ratio were measured in accordance with the provisions of the Pharmacopoeia of the People's Republic of China

[76] for nasal preparations and suspension preparations. The pH value and sedimentation volume ratio of the high-dose pharmaceutical composition of the present invention (original drug), the low-dose pharmaceutical composition of the present invention (diluted to 1 volume with distilled water) and the control drug (diluted to 5% active ingredient with distilled water) involved in the study were measured respectively. The results are shown in Table 2-1. The pH value and sedimentation volume ratio of the drug met the requirements of the preparation.

[0033] Table 2-1 pH value and sedimentation volume ratio of each group of drugs

[0034] Example 3

[0035] A total of 96 patients with migraine without aura or with typical aura who visited the headache clinic of Dongzhimen Hospital of Beijing University of Chinese Medicine from March 2023 to February 2024 were collected as research subjects, and the effectiveness and safety of the pharmaceutical composition of the present invention in treating the acute phase of migraine were evaluated.

[0036] A total of 96 patients were included in the study, 5 patients withdrew their informed consent after randomization, and 91 patients and 257 episodes were included in the statistical analysis. Compared with placebo, the pharmaceutical composition of the present invention and the diluted pharmaceutical composition of the present invention can increase the proportion of patients without headache for 2 hours (high dose 14.61%, low dose 17.65%, placebo 1.20%, P<0.0167) and the proportion of patients without headache for 4 hours (high dose 23.60%, low dose 28.24%, placebo 7.23%, P<0.0167); increase the proportion of patients with headache relief for 2 hours (high dose 64.04%, low dose 67.06%, placebo 24.10%, P<0.0167); shorten the onset time (high dose 18.64±37.49 minutes, low dose 30.02±62.35 minutes, placebo 263.80±445.22 minutes, P<0.001); and have no significant improvement on the proportion of headache recurrence within 24 hours and 48 hours. The pharmaceutical composition of the present invention has therapeutic effects on patients with different syndromes and different pain sites, but there is no significant difference in efficacy between different syndromes or different pain sites (P>0.05), and it has a tendency to improve pain in the temple, vertex, and forehead. In the study, symptoms including nasal burning, nasal irritation, nasal itching, nasal pain, pharyngeal burning, pharyngeal irritation, sneezing, and runny nose appeared, all of which were mild discomforts that disappeared after stopping the drug or washing the nasal cavity with clean water. The use of the pharmaceutical composition of the present invention will cause more adverse reactions than the use of the diluted pharmaceutical composition of the present invention. The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions only describe the principles of the present invention. The present invention may be subject to various changes and improvements without departing from the spirit and scope of the present invention. These changes and improvements fall within the scope of the present invention. The scope of protection claimed by the present invention is defined by the attached claims and their equivalents.

Claims

1. A Chinese medicine composition for external use for treating migraine, characterized in that: The composition is a medicine prepared from raw materials in the following weight proportion: 16-30 parts of fresh radish roots, 8-15 parts of ginger, 1-3 parts of fresh mint leaves and 0.3-2 parts of clove powder.

2. The Chinese medicine composition according to claim 1, characterized in that: The preferred weight ratio is: 24 parts of fresh radish roots, 12 parts of ginger, 2 parts of fresh mint leaves, and 1 part of clove powder.

3. The method for preparing the Chinese medicine composition according to claim 1, characterized in that: (1) Weigh the raw Chinese medicinal materials according to the above amounts; (2) Mix and mash the above-mentioned fresh radish roots, ginger and fresh mint leaves, and filter to obtain juice; (3) Pass clove powder through a 100-mesh sieve and add it to the medicine juice in step (2); (4) Mix thoroughly and filter using filter paper; (5) Dilute the filtrate with distilled water until the pH is in the range of 5.5-6.

5.

4. The Chinese medicine composition according to claim 1, characterized in that: The composition is used in nasal inhalants.

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