CN104474040B - Traditional Chinese medicine composition with effect of preventing and treating migraine as well as preparation method and application thereof - Google Patents
Traditional Chinese medicine composition with effect of preventing and treating migraine as well as preparation method and application thereof Download PDFInfo
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- CN104474040B CN104474040B CN201410680071.0A CN201410680071A CN104474040B CN 104474040 B CN104474040 B CN 104474040B CN 201410680071 A CN201410680071 A CN 201410680071A CN 104474040 B CN104474040 B CN 104474040B
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- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
- A23L2/38—Other non-alcoholic beverages
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- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
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- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
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- A—HUMAN NECESSITIES
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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Abstract
The invention belongs to the field of traditional Chinese medicine research and development, and particularly relates to a traditional Chinese medicine composition for preventing and treating migraine diseases, which is prepared by screening a traditional Chinese medicine clinical proved formula Xiongshao prescription medicine, wherein the Xiongshao prescription medicine is obtained by carrying out solvent extraction and macroporous adsorption resin purification and enrichment on the Xiongshao prescription, and the main components are amino acids, phenolic acids, phthalides, terpenes and alkaloids.
Description
Technical Field
The invention relates to a traditional Chinese medicine substance combination, in particular to a traditional Chinese medicine substance combination with the function of preventing and treating migraine and a method for simultaneously preparing the combination, belonging to the field of medicine research and development.
Background
Migraine is a common clinical disease characterized by severe headache, or recurrent attacks on the left or right, with frequently encountered diseases. Epidemiological investigation shows that the incidence rate of migraine in China is 985.2/10 ten thousand, the annual incidence rate is 79.5/10 ten thousand, the incidence rate of the migraine in the age group of more than 30 years old tends to rise year by year, the economic loss caused by the age group is up to $ 130 hundred million all year round, the exact pathophysiological mechanism of the migraine attack by western medicines is not very clear at present, although some western medicines such as 5-hydroxytryptamine receptor agonist, ergotamine medicine, non-steroidal anti-inflammatory drug and opioid analgesic have great progress in relieving the acute attack of the migraine, the western medicines are only symptomatic treatment and can not radically cure the migraine, and the symptomatic treatment is not effective for patients with the migraine.
The migraine belongs to the categories of headache, cerebral apoplexy, head wind, syncope headache, true headache, head wind and the like in the traditional Chinese medicine. The traditional Chinese medicine for treating migraine has a history of Yuan, accumulates abundant clinical application experiences, firstly, the ' headache ' disease is proposed from the ' all-cause disease theory, headache and facial wind syndrome ' of Suo ' yuan formula, and the clinical symptoms of headache are described in more detail from the ' Ren religious purification direct prescription ' of Song Dynasty Yan. Li Dongyuan (Dongyuan Shi book. differentiation of internal injury) classifies headache into headache due to external infection and headache due to internal injury, and clearly indicates the names of migraine: the migraine is also. The traditional Chinese medicine for treating migraine has the characteristics of definite curative effect, low toxicity, few side effects, obvious treatment effect and low recurrence rate.
The invention explores and discovers a traditional Chinese medicine substance combination with the migraine-resistant effect by taking the clinical proved formula of chuanxiong and peony as the formula source, and establishes a stable, reliable, practical and simultaneously-prepared process and a scientific and comprehensive quality control method by taking the type components and index components associated with the drug effect as comprehensive consideration, thereby being beneficial to the research and development of further innovative medicines. At present, no report related to the purification and preparation of the anti-migraine drug substance composition from the formula of chuanxiong peony and no report related to the research and the application of the composition in the aspect of treating migraine diseases are found.
Disclosure of Invention
The invention aims to provide a traditional Chinese medicine formula composition, which is prepared from ligusticum wallichii, white paeony root, goat horn and the like.
The invention also aims to provide a traditional Chinese medicine substance composition with the effect of preventing and treating migraine diseases, wherein the medicine system comprises terpenes, phenols, phthalides, alkaloids, amino acids and the like.
The invention also aims to provide a preparation method and a process thereof, and a third aim of the invention is to provide a quality detection and control method thereof. It is a fourth object of the present invention to provide its prophylactic and therapeutic activity against migraine diseases. The fifth purpose of the invention is to provide a product of the traditional Chinese medicine substance composition and application thereof in the field of medicines.
The purpose of the invention is realized by the following ways:
the Chinese medicine substance composition of the invention can be prepared by 3 groups of medicinal plants (animals) and substitute varieties thereof, including medicinal parts and non-medicinal parts thereof, medicinal materials and decoction pieces thereof, and a medicine system mainly comprises terpenes, phenols, phthalides, alkaloids and amino acids.
Group 1: ligusticum wallichii, and other similar plants in the same genus and family of Umbelliferae;
group 2: paeonia plant such as radix Paeoniae alba and radix Paeoniae Rubra, and Ranunculaceae family plant;
group 3: cornu Naemorhedi medicinal materials and bovine cognac medicinal materials such as cornu Naemorhedi, cornu Saigae Tataricae, small tailed Han sheep horn, and yellow sheep horn;
the traditional Chinese medicine substance combination can be obtained by combining the raw materials, extracting with ethanol, other alcohols, diluted alcohol, other organic solvents or water, and purifying by macroporous adsorption resin or other chromatographic methods, such as polyamide chromatography, or solvent extraction.
The traditional Chinese medicine substance combination can be prepared by further enriching and purifying the extracts of the raw material medicines or mixing the macroporous resin preparations of the raw material medicines.
The traditional Chinese medicine substance combination can be obtained by chemical synthesis or structural modification, biosynthesis or biological transfer and the like.
The traditional Chinese medicine composition is preferably prepared from the following raw material medicines:
50-200 parts of ligusticum wallichii, 50-200 parts of white peony root, 50-200 parts of goat horn
The preparation method of the traditional Chinese medicine substance combination comprises the following steps;
step 1: selecting rhizoma Ligustici Chuanxiong and radix Paeoniae alba as raw materials;
step 2: extracting with ethanol;
and step 3: purifying with macroporous adsorption resin;
and 4, step 4: extracting goat horn with water;
and 5: mixing the extract of rhizoma Ligustici Chuanxiong, radix Paeoniae alba and cornu Naemorhedi at a certain ratio
The content of terpenoid component in the traditional Chinese medicine substance combination is 1-50%, wherein the content of paeoniflorin is 0.1-10%; more than 0.5 to 50 percent of phenolic acid component, wherein the content of ferulic acid is 0.1 to 10 percent, the content of phthalide component is more than 0.1 to 50 percent, wherein the content of senkyunolide I is 0.01 to 10 percent, the content of alkaloid component is 0.1 to 50 percent, and the content of amino acid component is 1 to 50 percent.
In the step 2, the ligusticum wallichii and the white paeony root are refluxed and extracted for 1 to 5 times by 5 to 15 times of 40 to 80 percent ethanol, each time lasts for 0.5 to 2.5 hours, the filtration is carried out, the filtrates are combined, the reduced pressure concentration is carried out until no alcohol smell exists, and 300 to 800 parts by weight of water is added for dilution, so that the concentration of the sample loading liquid is 0.01 to 0.1 g/ml.
In the step 3, enabling the sample loading solution to pass through a low-polarity or polar macroporous adsorption resin, enabling the adsorption flow rate to be 1-5 BV/h, enabling the column diameter height ratio of the resin to be 1: 4-10, enabling the concentration of the sample loading solution to be 0.02-0.1 g/mL, eluting 1-5 times of the volume of the resin with water to remove impurities, enabling the water impurity removal flow rate to be 1-5 BV/h, eluting 3-10 times of the volume of the resin with 10-60% of ethanol, enabling the elution flow rate to be 1-5 BV/h, collecting ethanol eluent, recovering a solvent, and drying under reduced pressure to obtain effective components of phenolic acids, terpenes, alkaloids and amino acids; eluting with 60-95% ethanol at a flow rate of 1-5 BV/h for 3-15 times of the resin volume, collecting the ethanol eluate, recovering the solvent, and drying under reduced pressure to obtain the phthalides active ingredient.
The macroporous adsorption resin used in the step 3 is preferably AB-8, D101, HPD-100 type or other weak polar or nonpolar macroporous resin.
And 4, refluxing and extracting the goat horn for 1-5 times by using 10-100 times of water in the step 4, wherein each time lasts for 1-5 hours, filtering, combining the filtrates, recovering the solvent, evaporating to dryness, and drying in vacuum.
The three parts of traditional Chinese medicine substances are subjected to compatibility and combination, conventional auxiliary materials are added, and any pharmaceutically acceptable conventional preparation formulation including capsules, tablets, granules, gels, sustained release agents, oral liquid and the like is prepared according to a conventional preparation process.
The principles and features of this invention are described below in conjunction with examples which are set forth to illustrate, but are not to be construed to limit the scope of the invention.
Experimental example 1: anti-migraine effect of effective component on rats with partial headache caused by nitroglycerin
70 SD rats with half male and female, 7 groups, 10 rats in each group, blank group, model group, control group 1 (Zhengtian pill group), control group 2 (Tianshu capsule group), water extract group, alcohol preparation group. Duplicating nitroglycerin migraine model (10mg/kg), performing intragastric administration immediately after modeling, performing abdominal aorta blood drawing immediately after 15min, centrifuging to obtain blood plasma, taking brain, and determining calcitonin gene-related phthalein Content (CPGR) in brain (measured by ELISA method), endothelin content (ET-1) (measured by ELISA method), and 5-hydroxytryptamine (5-HT) content in blood plasma.
The experimental results are as follows: comparison of 5-HT levels in plasma and CGRP, ET-1 in brain in various groups of rats
Note: p < 0.01 compared to model group.
Conclusion
Compared with the model group, the traditional Chinese medicine preparation group can reduce the 5-HT content in the plasma of a model rat, the calcitonin gene-related phthalein content in the brain of the rat and the endothelin content in the brain of the rat, thereby preventing and treating migraine.
Formulations containing the preparations proposed by the present invention can be prepared according to methods well known in the art. The preparations proposed by the present invention can be combined with one or more solid or liquid pharmaceutical excipients and/or adjuvants, to make suitable administration forms or dosage forms for use as human or veterinary medicine.
The preparation containing the preparation provided by the invention can be administrated in a unit dosage form, and the administration route can be intestinal tract or parenteral tract, such as oral administration, muscle, nasal cavity, oral mucosa, skin, transdermal, subcutaneous, intradermal, peritoneal, rectal and the like. The administration dosage form can be liquid dosage form, solid dosage form, such as liquid dosage form can be true solution dosage form, colloid solution dosage form, microparticle dosage form, emulsion dosage form, suspension dosage form. The liquid dosage form can be syrup, medicated wine, injection solution, non-aqueous solution, suspension or emulsion, etc.; solid dosage forms such as tablets, troches, capsules, dripping pills, granules, powders, creams, suppositories, powders, ointments and the like.
The preparation containing the preparation provided by the invention can be a common preparation, and also can be a sustained-release preparation, a controlled-release preparation, a targeting preparation, various particle drug delivery systems and the like.
In order to prepare the unit dosage form into tablets, various carriers well known in the art can be widely used. Examples of the carrier include excipients such as calcium carbonate, lactose, calcium phosphate, sodium phosphate; diluents and absorbents such as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, urea, calcium carbonate, kaolin, microcrystalline cellulose, aluminum silicate, dextran, colloidal silicon dioxide, gum arabic, gelatin, magnesium trisilicate, keratin, and the like; wetting agents and binders such as water, glycerin, polyethylene glycol, ethanol, propanol, starch slurry, dextrin, syrup, honey, glucose solution, acacia slurry, gelatin slurry, sodium carboxymethylcellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone and the like; disintegrating agent such as dried starch, sodium alginate, agar powder, brown algae starch, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene sorbitol fatty acid ester, sodium dodecyl sulfate, methylcellulose, and ethyl cellulose; disintegration inhibitors such as sucrose, glyceryl tristearate, cacao ester, hydrogenated vegetable oil, etc.; absorption accelerators such as quaternary ammonium salts, sodium lauryl sulfate and the like; lubricants such as talc, triethylamine magnesium stearate, triethylamine stearic acid, silica, corn starch, stearate, boric acid, liquid paraffin, polyethylene glycol, and the like. The tablet can be further made into coated tablet, such as sugar-coated tablet, film-coated tablet, enteric-coated tablet, or double-layer tablet and multi-layer tablet.
In order to prepare the dosage form for unit administration into a pill, various carriers well known in the art can be widely used. Examples of the carrier are, for example, diluents and absorbents such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, polyvinylpyrrolidone, kaolin, talc and the like; binding agent such as acacia, tragacanth, gelatin, ethanol, honey, rice paste or flour paste; disintegrating agent such as agar powder, dried starch, sodium alginate, sodium dodecyl sulfate, methyl cellulose, ethyl cellulose, etc.
For the encapsulation of unit dosage forms, the preparations proposed by the present invention can be mixed with the various carriers mentioned above and the mixture thus obtained placed in hard gelatin capsules or soft capsules. The preparation provided by the invention can also be prepared into microcapsules, suspended in an aqueous medium to form a suspension, and can also be filled into hard capsules or prepared into injections for application.
In order to prepare the unit dosage form into oral liquid preparations such as emulsion, solution, suspension, syrup, etc., additives such as coloring agent, preservative, emulsifier, suspending agent, flavoring agent (e.g., peppermint, wintergreen oil, etc.), sweetener (e.g., sucrose, lactose, etc.) or other materials may be optionally added as necessary.
In order to make the unit dosage form into aqueous or non-aqueous preparation for injection, such as solution, suspension solution, emulsion, lyophilized powder for injection, one or more pharmaceutically acceptable carriers, such as diluent, wetting agent, emulsifier, lubricant, antiseptic, surfactant or dispersant, and conventional cosolvent, buffer, pH regulator, etc., can be added. The diluent is selected from water, ethanol, polyethylene glycol, 1, 3-propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, vegetable oil (such as olive oil, corn oil, etc.), gelatin, injectable organic ester (such as ethyl oleate, fatty acid ester, etc.), polyoxyethylene sorbitol, etc. In order to prepare the isotonic injection, a proper amount of sodium chloride, glucose or glycerol can be added.
The following examples further illustrate the compatible Chinese medicinal materials and their preparation methods, but the present invention is not limited to the contents of the following examples.
Example 1: preparation process of traditional Chinese medicine substance combination for preventing and treating migraine
333.4g of ligusticum wallichii, 333.4g of white peony root, 333.3g of goat horn, 333.3g
Taking 0.6667kg of rhizoma Ligustici Chuanxiong and radix Paeoniae alba decoction pieces according to the above proportion, reflux-extracting with 8 times of 50% ethanol for 2 times, each time for 1 hr, and recovering solvent under reduced pressure to obtain extract; adding water for dispersing and dissolving to make the concentration of the aqueous solution be 0.05g/mL (calculated by converted medicinal materials, wherein the ferulic acid content is 0.0180mg/mL, the chlorogenic acid content is 0.0278mg/mL, the caffeic acid content is 0.0010mg/mL, the senkyunolide I content is 0.0223mg/mL, the senkyunolide H content is 0.0038mg/mL, and the paeoniflorin content is 0.2283mg/mL), passing through 6.1L AB-8 type macroporous adsorption resin, the adsorption flow rate is 2BV/H, the height ratio of the resin column diameter is 1: 6, the concentration of the sample liquid is 0.05g/mL, washing 1 time of the resin volume for removing impurities, the impurity removal flow rate is 3BV/H, 50% ethanol is 6 times of the resin volume, the elution flow rate is 2BV/H, collecting 50% ethanol, recovering the solvent, and drying under reduced pressure to obtain phenolic acids, terpenes and total alkaloids; eluting with 90% ethanol at flow rate of 2BV/h for 7 times of resin volume in the resin column, collecting 90% ethanol eluate, recovering solvent, and drying under reduced pressure to obtain phthalide components; extracting 0.3333g cornu Naemorhedi with 50 times of water for 3 hr, recovering solvent, and drying under reduced pressure to obtain amino acids. Mixing the three materials at a ratio of 1: 1, adding conventional adjuvants, and making into capsule according to conventional process.
Method for measuring contents of phenolic acids, terpenoids, phthalides, alkaloids and amino acids
Comparison products: ferulic acid, paeoniflorin, senkyunolide I, ligustrazine hydrochloride, and glutamic acid
A chromatographic column: thermal analysis column GOLD-C18; flow rate: 1.0 mL/min; column temperature: 30 ℃; detection wavelength: 210-400 nm; mobile phase: methanol-0.2% formic acid
Gradient condition
The content of phenolic acid in the enriched substance is determined to be more than 13.5 percent, and the content of ferulic acid is not less than 0.63 percent; the terpenoid component content is more than 28.5%, and the paeoniflorin content is not less than 9.4%; the phthalide component content is more than 1.5%, and the senkyunolide I content is not less than 0.8%; the content of alkaloid components reaches more than 4.4 percent; the content of amino acid components is more than 5.0%.
Example 2: preparation process of traditional Chinese medicine substance combination for preventing and treating migraine
333.4g of ligusticum wallichii, 333.4g of white peony root, 333.3g of goat horn, 333.3g
Taking 0.6667kg of rhizoma Ligustici Chuanxiong and radix Paeoniae alba decoction pieces according to the above proportion, reflux-extracting with 8 times of 60% ethanol for 1 time, each time for 0.5 hr, and recovering solvent under reduced pressure to obtain extract; adding water for dispersing and dissolving to make the concentration of the aqueous solution be 0.05g/mL (calculated by converted medicinal materials, wherein the ferulic acid content is 0.0180mg/mL, the chlorogenic acid content is 0.0278mg/mL, the caffeic acid content is 0.0010mg/mL, the senkyunolide I content is 0.0223mg/mL, the senkyunolide H content is 0.0038mg/mL, and the paeoniflorin content is 0.2283mg/mL), passing through 6.1L AB-8 type macroporous adsorption resin, the adsorption flow rate is 2BV/H, the height ratio of the resin column diameter is 1: 6, the concentration of the sample liquid is 0.05g/mL, washing 1 time of the resin volume for removing impurities, the impurity removal flow rate is 3BV/H, 50% ethanol is 6 times of the resin volume, the elution flow rate is 2BV/H, collecting 50% ethanol, recovering the solvent, and drying under reduced pressure to obtain phenolic acids, terpenes and total alkaloids; eluting with 90% ethanol at flow rate of 2BV/h for 7 times of resin volume in the resin column, collecting 90% ethanol eluate, recovering solvent, and drying under reduced pressure to obtain phthalide components; extracting 0.3333g cornu Naemorhedi with 50 times of water for 3 hr, recovering solvent, and drying under reduced pressure to obtain amino acids. Mixing the three materials at a ratio of 1: 1, adding conventional adjuvants, and making into capsule according to conventional process.
Method for measuring contents of phenolic acids, terpenoids, phthalides, alkaloids and amino acids
Comparison products: ferulic acid, paeoniflorin, senkyunolide I, ligustrazine hydrochloride, and glutamic acid
A chromatographic column: thermal analysis column GOLD-C18; flow rate: 1.0 mL/min; column temperature: 30 ℃; detection wavelength: 210-400 nm; mobile phase: methanol-0.2% formic acid
Gradient condition
The content of phenolic acid in the enriched substance is determined to be more than 13.5 percent, and the content of ferulic acid is not less than 0.63 percent; the terpenoid component content is more than 28.5%, and the paeoniflorin content is not less than 9.4%; the phthalide component content is more than 1.5%, and the senkyunolide I content is not less than 0.8%; the content of alkaloid components reaches more than 4.4 percent; the content of amino acid components is more than 5.0%.
Example 3: preparation process of traditional Chinese medicine substance combination for preventing and treating migraine
333.4g of ligusticum wallichii, 333.4g of white peony root, 333.3g of goat horn, 333.3g
Taking 0.6667kg of rhizoma Ligustici Chuanxiong and radix Paeoniae alba decoction pieces according to the above proportion, reflux-extracting with 8 times of 40% ethanol for 3 times, each time for 1 hr, and recovering solvent under reduced pressure to obtain extract; adding water for dispersing and dissolving to make the concentration of the aqueous solution be 0.05g/mL (calculated by converted medicinal materials, wherein the ferulic acid content is 0.0180mg/mL, the chlorogenic acid content is 0.0278mg/mL, the caffeic acid content is 0.0010mg/mL, the senkyunolide I content is 0.0223mg/mL, the senkyunolide H content is 0.0038mg/mL, and the paeoniflorin content is 0.2283mg/mL), passing through 6.1L AB-8 type macroporous adsorption resin, the adsorption flow rate is 2BV/H, the height ratio of the resin column diameter is 1: 6, the concentration of the sample liquid is 0.05g/mL, washing 1 time of the resin volume for removing impurities, the impurity removal flow rate is 3BV/H, 55% ethanol is 6 times of the resin volume, the elution flow rate is 2BV/H, collecting 55% ethanol, recovering the solvent, and drying under reduced pressure to obtain phenolic acids, terpenes and total alkaloids; eluting with 95% ethanol at flow rate of 2BV/h for 7 times of the resin volume in the resin column, collecting 95% ethanol eluate, recovering solvent, and drying under reduced pressure to obtain phthalide components; extracting 0.3333g cornu Naemorhedi with 50 times of water for 3 hr, recovering solvent, and drying under reduced pressure to obtain amino acids. Mixing the three materials at a ratio of 1: 1, adding conventional adjuvants, and making into capsule according to conventional process.
Method for measuring contents of phenolic acids, terpenoids, phthalides, alkaloids and amino acids
Comparison products: ferulic acid, paeoniflorin, senkyunolide I, ligustrazine hydrochloride, and glutamic acid
A chromatographic column: thermal analysis column GOLD-C18; flow rate: 1.0 mL/min; column temperature: 30 ℃; detection wavelength: 210-400 nm; mobile phase: methanol-0.2% formic acid
Gradient condition
The content of phenolic acid in the enriched substance is determined to be more than 13.5 percent, and the content of ferulic acid is not less than 0.63 percent; the terpenoid component content is more than 28.5%, and the paeoniflorin content is not less than 9.4%; the phthalide component content is more than 1.5%, and the senkyunolide I content is not less than 0.8%; the content of alkaloid components reaches more than 4.4 percent; the content of amino acid components is more than 5.0%.
Example 4: preparation process of traditional Chinese medicine substance combination for preventing and treating migraine
333.4g of ligusticum wallichii, 333.4g of white peony root, 333.3g of goat horn, 333.3g
Taking 0.6667kg of rhizoma Ligustici Chuanxiong and radix Paeoniae alba decoction pieces according to the above proportion, reflux-extracting with 8 times of 50% ethanol for 2 times, each time for 1 hr, and recovering solvent under reduced pressure to obtain extract; adding water for dispersing and dissolving to make the concentration of the aqueous solution be 0.05g/mL (calculated by the converted medicinal material, wherein the ferulic acid content is 0.0180mg/mL, the chlorogenic acid content is 0.0278mg/mL, the caffeic acid content is 0.0010mg/mL, the senkyunolide I content is 0.0223mg/mL, the senkyunolide H content is 0.0038mg/mL, and the paeoniflorin content is 0.2283mg/mL), passing through 6.1LHPD100 type macroporous adsorbent resin, the adsorption flow rate is 2BV/H, the height ratio of the resin column diameter is 1: 6, the concentration of the sample loading solution is 0.05g/mL, eluting by 1 time of the resin volume for removing impurities, the elution flow rate is 3BV/H, eluting by 50% ethanol by 6 times of the resin volume, the elution flow rate is 2BV/H, collecting 50% ethanol, recovering the solvent, and drying under reduced pressure to obtain total phenolic acid, terpenoid and alkaloid; eluting with 90% ethanol at flow rate of 2BV/h for 7 times of resin volume in the resin column, collecting 90% ethanol eluate, recovering solvent, and drying under reduced pressure to obtain phthalide components; extracting 0.3333g cornu Naemorhedi with 50 times of water for 3 hr, recovering solvent, and drying under reduced pressure to obtain amino acids. Mixing the three materials at a ratio of 1: 1, adding conventional adjuvants, and making into capsule according to conventional process.
Method for measuring contents of phenolic acids, terpenoids, phthalides, alkaloids and amino acids
Comparison products: ferulic acid, paeoniflorin, senkyunolide I, ligustrazine hydrochloride, and glutamic acid
A chromatographic column: thermal analysis column GOLD-C18; flow rate: 1.0 mL/min; column temperature: 30 ℃; detection wavelength: 210-400 nm; mobile phase: methanol-0.2% formic acid
Gradient condition
The content of phenolic acid in the enriched substance is determined to be more than 13.5 percent, and the content of ferulic acid is not less than 0.63 percent; the terpenoid component content is more than 28.5%, and the paeoniflorin content is not less than 9.4%; the phthalide component content is more than 1.5%, and the senkyunolide I content is not less than 0.8%; the content of alkaloid components reaches more than 4.4 percent; the content of amino acid components is more than 5.0%.
Example 5: preparation process of traditional Chinese medicine substance combination for preventing and treating migraine
333.4g of ligusticum wallichii, 333.4g of white peony root, 333.3g of goat horn, 333.3g
Taking 0.6667kg of rhizoma Ligustici Chuanxiong and radix Paeoniae alba decoction pieces according to the above proportion, reflux-extracting with 8 times of 50% ethanol for 2 times, each time for 1 hr, and recovering solvent under reduced pressure to obtain extract; adding water for dispersing and dissolving to make the concentration of the aqueous solution be 0.05g/mL (calculated by converted medicinal materials, wherein the ferulic acid content is 0.0180mg/mL, the chlorogenic acid content is 0.0278mg/mL, the caffeic acid content is 0.0010mg/mL, the senkyunolide I content is 0.0223mg/mL, the senkyunolide H content is 0.0038mg/mL, and the paeoniflorin content is 0.2283mg/mL), passing through 6.1L AB-8 type macroporous adsorption resin, the adsorption flow rate is 2BV/H, the height ratio of the resin column diameter is 1: 8, the concentration of the sample liquid is 0.05g/mL, washing 1 time of the resin volume for removing impurities, the impurity removal flow rate is 3BV/H, the 40% ethanol elution 8 times of the resin volume, the elution flow rate is 2BV/H, collecting 40% ethanol, recovering the solvent, and drying under reduced pressure to obtain phenolic acids, terpenes and total alkaloids; eluting with 80% ethanol at flow rate of 2BV/h for 10 times of the resin volume in the resin column, collecting 80% ethanol eluate, recovering solvent, and drying under reduced pressure to obtain phthalide components; extracting 0.3333g cornu Naemorhedi with 50 times of water for 3 hr, recovering solvent, and drying under reduced pressure to obtain amino acids. Mixing the three materials at a ratio of 1: 1, adding conventional adjuvants, and making into capsule according to conventional process.
Method for measuring contents of phenolic acids, terpenoids, phthalides, alkaloids and amino acids
Comparison products: ferulic acid, paeoniflorin, senkyunolide I, ligustrazine hydrochloride, and glutamic acid
A chromatographic column: thermal analysis column GOLD-C18; flow rate: 1.0 mL/min; column temperature: 30 ℃; detection wavelength: 210-400 nm; mobile phase: methanol-0.2% formic acid
Gradient condition
The content of phenolic acid in the enriched substance is determined to be more than 13.5 percent, and the content of ferulic acid is not less than 0.63 percent; the terpenoid component content is more than 28.5%, and the paeoniflorin content is not less than 9.4%; the phthalide component content is more than 1.5%, and the senkyunolide I content is not less than 0.8%; the content of alkaloid components reaches more than 4.4 percent; the content of amino acid components is more than 5.0%.
Example 6: preparation of capsules
Taking 200g of the traditional Chinese medicine composition, crushing, sieving by a 80-mesh sieve, uniformly mixing with 100g of microcrystalline cellulose, granulating by 95% ethanol, drying, grading by a 20-mesh sieve, and filling into capsules.
Example 7: preparation of tablets
Taking 50g of the traditional Chinese medicine composition, crushing, sieving by a 80-mesh sieve, uniformly mixing with 70g of microcrystalline cellulose and 5g of sodium carboxymethyl starch, granulating by 5% PVP, drying, granulating by a 20-mesh sieve, adding 2g of magnesium stearate, and tabletting.
Example 8: preparation of dripping pills
The preparation method comprises the steps of combining 60g of the traditional Chinese medicine substances, crushing, sieving with a 80-mesh sieve, uniformly mixing, putting 180g of heated and melted polyethylene glycol 6000, stirring until the mixture is dissolved, transferring the mixture into a liquid storage bottle, sealing and keeping the temperature at 80-90 ℃, adjusting a liquid drop quantitative valve of a pill dropping machine, dropping the mixture into liquid paraffin with the temperature of 10-15 ℃ from top to bottom, draining the formed dropping pills, wiping off the liquid paraffin, and drying.
Example 9: preparation of oral liquid
Taking 70g of the traditional Chinese medicine composition, crushing, sieving with a 80-mesh sieve, uniformly mixing, mixing with 1000g of honey, 200g of cane sugar, 10g of sodium benzoate and 2000ml of distilled water, heating to 85-90 ℃, stirring for dissolving, keeping the temperature for 30min, filtering, adding water into filtrate for diluting to 4000ml, uniformly stirring, filling and sealing, and sterilizing.
Example 10: preparation of injection
Taking 100g of the traditional Chinese medicine composition, adding a proper amount of water for injection to dissolve the composition, adding 0.02% of activated carbon in a configured amount, stirring for 5-10 min, filtering, diluting the filtrate to about 10L, adding sodium chloride to adjust osmotic pressure to be isotonic, adjusting pH to 7.5-8.0, performing ultrafiltration, filling and sealing, and sterilizing at 100 ℃ for 30 min.
Example 11: preparation of powder injection
Taking 100g of the traditional Chinese medicine composition, adding an appropriate amount of water for injection and dilute sodium hydroxide to dissolve, adding 0.02% of activated carbon in a prepared amount, stirring for 5-10 min, filtering, diluting the filtrate to 1L, adjusting the pH to 6.5-7.8, performing ultrafiltration, performing spray drying, and performing sterile packaging on dry powder. Each 100mg of the injection solution is dissolved by adding a proper amount of water for injection before use, diluted by 250-500 ml of sodium chloride infusion solution and slowly instilled into veins.
Claims (3)
1. A traditional Chinese medicine composition with the effect of preventing and treating migraine is characterized in that the preparation method of the traditional Chinese medicine composition comprises the following steps:
step 1: selecting 50-200 parts by weight of Sichuan peony root and 50-200 parts by weight of white peony root;
step 2: reflux-extracting rhizoma ligustici wallichii and radix paeoniae alba for 1-5 times by 5-15 times of 40-80% ethanol, filtering, combining filtrates, concentrating under reduced pressure until no alcohol smell exists, and adding 300-800 parts by weight of water for dilution to enable the concentration of a sample loading solution to be 0.01-0.1 g/ml;
and step 3: enabling the sample loading solution to pass through a low-polarity or polar macroporous adsorption resin, enabling the adsorption flow rate to be 1-5 BV/h, enabling the height ratio of the column diameter of the resin to be 1: 4-10, enabling the concentration of the sample loading solution to be 0.02-0.1 g/mL, removing impurities by eluting with water by 1-5 times the volume of the resin, enabling the water impurity removal flow rate to be 1-5 BV/h, eluting with 10-60% of ethanol by 3-10 times the volume of the resin, enabling the elution flow rate to be 1-5 BV/h, collecting ethanol eluent, recovering a solvent, and drying under reduced pressure to obtain effective components of phenolic acids, terpenes, alkaloids and amino acids; eluting with 60-95% ethanol at a flow rate of 1-5 BV/h for 3-15 times of the resin volume, collecting the ethanol eluate, recovering the solvent, and drying under reduced pressure to obtain the phthalides active component;
and 4, step 4: taking 50-200 parts by weight of goat horn, extracting with 10-100 times of water under reflux for 1-5 times, each time for 1-5 hours, filtering, combining filtrates, recovering solvent, evaporating to dryness, and vacuum drying
And 5: mixing the phenolic acid, terpenoid, alkaloid, amino acid effective components and phthalide effective components obtained in the step 3 with the part obtained in the step 4 according to the ratio of 1: 1;
the content of phenolic acid in the Chinese medicinal composition is more than 13.5%, and the content of ferulic acid is more than 0.63%; the terpenoid component content is above 28.5%, and the paeoniflorin content is above 9.4%; phthalide component content is above 1.5%, and ligustilide I content is above 0.8%; the content of alkaloid components is more than 4.4%; the content of amino acids is above 5.0%.
2. The traditional Chinese medicine composition of claim 1, wherein the raw materials in steps 1 and 4 comprise: 333.4g of Sichuan peony root, 333.3g of white peony root and 333.3g of goat horn.
3. The traditional Chinese medicine composition of claim 1, wherein various pharmaceutical excipients known in the art can be added to prepare any pharmaceutically acceptable conventional dosage form according to a conventional preparation process.
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