CN118286356A - Traditional Chinese medicine composition for treating headache and application thereof - Google Patents
Traditional Chinese medicine composition for treating headache and application thereof Download PDFInfo
- Publication number
- CN118286356A CN118286356A CN202410247229.9A CN202410247229A CN118286356A CN 118286356 A CN118286356 A CN 118286356A CN 202410247229 A CN202410247229 A CN 202410247229A CN 118286356 A CN118286356 A CN 118286356A
- Authority
- CN
- China
- Prior art keywords
- parts
- headache
- traditional chinese
- medicine composition
- chinese medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 54
- 206010019233 Headaches Diseases 0.000 title claims abstract description 51
- 231100000869 headache Toxicity 0.000 title claims abstract description 47
- 239000000203 mixture Substances 0.000 title claims abstract description 35
- 241001522129 Pinellia Species 0.000 claims abstract description 18
- 241000132012 Atractylodes Species 0.000 claims abstract description 17
- 235000002722 Dioscorea batatas Nutrition 0.000 claims abstract description 17
- 235000006536 Dioscorea esculenta Nutrition 0.000 claims abstract description 17
- 240000001811 Dioscorea oppositifolia Species 0.000 claims abstract description 17
- 235000003416 Dioscorea oppositifolia Nutrition 0.000 claims abstract description 17
- 241000037740 Coptis chinensis Species 0.000 claims abstract description 16
- 244000111489 Gardenia augusta Species 0.000 claims abstract description 16
- 241001071795 Gentiana Species 0.000 claims abstract description 16
- 241000241550 Cyathula Species 0.000 claims abstract description 15
- 241000237502 Ostreidae Species 0.000 claims abstract description 15
- 240000005001 Paeonia suffruticosa Species 0.000 claims abstract description 15
- 235000003889 Paeonia suffruticosa Nutrition 0.000 claims abstract description 15
- 235000020636 oyster Nutrition 0.000 claims abstract description 15
- 235000021028 berry Nutrition 0.000 claims abstract description 14
- 241000405414 Rehmannia Species 0.000 claims abstract description 12
- 244000236658 Paeonia lactiflora Species 0.000 claims abstract description 10
- 235000008598 Paeonia lactiflora Nutrition 0.000 claims abstract description 10
- 244000303040 Glycyrrhiza glabra Species 0.000 claims abstract description 8
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims abstract description 8
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims abstract description 8
- 235000011477 liquorice Nutrition 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 241000305492 Gastrodia Species 0.000 claims abstract description 6
- 241000212322 Levisticum officinale Species 0.000 claims abstract description 6
- 240000008866 Ziziphus nummularia Species 0.000 claims abstract description 6
- 239000001645 levisticum officinale Substances 0.000 claims abstract description 6
- 235000018958 Gardenia augusta Nutrition 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 15
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 claims description 9
- 210000000582 semen Anatomy 0.000 claims description 9
- 239000008187 granular material Substances 0.000 claims description 8
- 235000006484 Paeonia officinalis Nutrition 0.000 claims description 7
- 241001106477 Paeoniaceae Species 0.000 claims description 7
- 239000006188 syrup Substances 0.000 claims description 5
- 235000020357 syrup Nutrition 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 3
- 241000305491 Gastrodia elata Species 0.000 claims description 2
- 241000112528 Ligusticum striatum Species 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 16
- 230000001717 pathogenic effect Effects 0.000 abstract description 9
- 229940126680 traditional chinese medicines Drugs 0.000 abstract description 2
- 238000002474 experimental method Methods 0.000 description 34
- 241000700159 Rattus Species 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 208000002193 Pain Diseases 0.000 description 20
- 230000036407 pain Effects 0.000 description 20
- 210000004185 liver Anatomy 0.000 description 16
- 238000001914 filtration Methods 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 14
- 239000008280 blood Substances 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 208000000114 Pain Threshold Diseases 0.000 description 12
- 230000007812 deficiency Effects 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 230000037040 pain threshold Effects 0.000 description 12
- 238000002156 mixing Methods 0.000 description 10
- 230000003542 behavioural effect Effects 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 210000000952 spleen Anatomy 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
- 206010027599 migraine Diseases 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 206010062717 Increased upper airway secretion Diseases 0.000 description 3
- 206010061245 Internal injury Diseases 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 208000031975 Yang Deficiency Diseases 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 230000009194 climbing Effects 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 208000026435 phlegm Diseases 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 2
- 239000000006 Nitroglycerin Substances 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 206010043269 Tension headache Diseases 0.000 description 2
- 208000008548 Tension-Type Headache Diseases 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229960003711 glyceryl trinitrate Drugs 0.000 description 2
- 208000013403 hyperactivity Diseases 0.000 description 2
- 238000010832 independent-sample T-test Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 235000019615 sensations Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- 208000019736 Cranial nerve disease Diseases 0.000 description 1
- 241000721047 Danaus plexippus Species 0.000 description 1
- 206010016059 Facial pain Diseases 0.000 description 1
- 208000027109 Headache disease Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 240000006079 Schisandra chinensis Species 0.000 description 1
- 208000031971 Yin Deficiency Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000030270 breast disease Diseases 0.000 description 1
- 230000001914 calming effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 208000014826 cranial nerve neuropathy Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 230000003860 sleep quality Effects 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 201000002282 venous insufficiency Diseases 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to a traditional Chinese medicine composition for treating headache, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition disclosed by the invention comprises the following raw materials in parts by weight: 15-25 parts of wild jujube seed, 10-20 parts of Chinese yam, 10-15 parts of bighead atractylodes rhizome, 5-15 parts of coptis chinensis, 5-15 parts of medicinal cyathula root, 15-30 parts of rehmannia root, 5-15 parts of shizandra berry, 5-12 parts of gentian, 10-20 parts of pinellia tuber, 5-15 parts of cape jasmine, 5-15 parts of tree peony bark, 10-15 parts of white peony root, 20-30 parts of oyster, 10-20 parts of szechuan lovage rhizome, 15-20 parts of tall gastrodia tuber and 5-10 parts of liquorice. The traditional Chinese medicine composition has a good treatment effect on intermittent headache, headache caused by exogenous pathogenic wind, perimenopausal headache and other headache caused by various reasons, and has obvious clinical treatment effect.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and relates to a traditional Chinese medicine composition for treating headache.
Background
Headache is one of the common symptoms of neurology portals and emergency. Headache disorders can be divided into 3 general categories, primary headache, secondary headache, and painful cranial neuropathy and other facial pain, as well as other types of headache. Headache is classified by WHO as the first 10 disabling disorder. Global lifelong prevalence of primary headaches is 64%. One study in China showed that the prevalence of primary headache was 23.8%, of which the prevalence of migraine was 9.3% and of tension headache was 10.8%. With the development of modern society, the life rhythm is accelerated, the work competition is more and more vigorous, the pressure of people is increased, and the incidence of primary headache is in an ascending trend. Epidemiological surveys, however, show that only 13.8% of migraine and 5.6% of tension headache are treated correctly. At present, the pathogenic factors and pathogenesis of primary headache are not completely known, western medicine lacks specific therapeutic drugs with pertinence, patient compliance is poor, and addictive drugs such as analgesic drugs are abused to form malignant circulation.
The etiology of headache in traditional Chinese medicine is divided into two categories, namely exogenous pathogenic factors and internal injury. Exogenous headache is usually caused by careless daily life and is marked by exogenous pathogenic factors such as wind, cold, dampness and heat. "Su Wen-Tai Yin Yang Ming Lun" cloud: the patient is injured by wind, and the patient is first born. Wind is a long disease and is easy to get involved in qi and cause diseases. The head is the house of the clear yang, and exogenous pathogenic factors such as wind, cold, dampness and heat can block the clear yang, qi and blood are not smooth, stagnate and clear orifices, pain is caused by obstruction, and headache is caused.
Headache is caused by viscera dysfunction. Both deficiency and excess syndromes can be transformed into each other under certain conditions. Headache due to internal injury is closely related to pathological factors such as qi, blood, phlegm, blood stasis, deficiency and the like, and can cause diseases singly or simultaneously. Chenglike "Zhengzhihuan-Tou Tong" cloud: the head is covered like a day, and qi of the three-yang six fu-organs and the blood of the three-yin five-organ essence are all infused. Therefore, six pathogenic factors caused by the weather and five thieves with the transformation of human qi can be mutually harmful.
Whether the exogenous headache or the internal injury headache belongs to the categories of migraine, headache and headache wind in traditional Chinese medicine, the main causative factors are: 1. feel exogenous pathogenic factors. Because of exogenous wind-cold, improper and incomplete treatment, wind evil remains, the body is hidden, the channels and collaterals are blocked, and the disease is long-lasting; or liver, spleen and viscera dysfunction due to cold and heat climate or emotional stimulation. 2. Liver fire is disturbing upward. Liver wind headache is caused by depression, anger and disturbance of channels and collaterals, and the clinical manifestations are explosive pain, severe pain or left or right, and eye and teeth. 3. Hyperactivity of liver-yang. Headache is caused by excessive internal fire of the liver, excessive internal fire damaging yin, liver failing to nourish the liver, liver-kidney yin deficiency, kidney-water deficiency, water failure to contain wood, liver-yang hyperactivity, and upward disturbance of the orifices. 4. Phlegm-stasis obstructing collaterals. Wind invasion is associated with venous stasis. Wind-stasis and blood-stasis pain are the main pathogenesis of this disease, and are mostly the deficiency with the excess of the middle energizer and the excess of the principal deficiency with the excess of the secondary deficiency. Therefore, it should be treated by resolving phlegm, inducing resuscitation, warming channels, promoting blood circulation and relieving pain. 5. Deficiency of qi and blood. The liver, spleen and kidney are damaged, yin and blood are not nourished due to liver deficiency, clear yang is not ascended due to spleen deficiency, qi and blood deficiency cannot be nourished in brain marrow and collaterals, liver and spleen are disordered, and clear orifices are malnourished due to qi and blood deficiency, so that headache is caused. 6. Deficiency of liver yang and kidney yang. The liver-yang deficiency is due to spleen-yang deficiency and kidney-yang deficiency. Cold is an internal sensation, stagnation of liver meridian, adverse liver and gallbladder meridian, and causes a fever with headache.
Ancient doctors paid importance to the theory of meridian tropism according to headache parts, and proper administration of the meridian guiding drugs can guide the drugs to the affected parts, so that the traditional Chinese medicine composition has better effect on headache treatment.
Disclosure of Invention
The invention aims at providing a traditional Chinese medicine composition capable of effectively treating various types of headache.
The invention adopts the following technical scheme to realize the purposes:
A traditional Chinese medicine composition comprises the following raw materials in parts by weight:
15-25 parts of wild jujube seed, 10-20 parts of Chinese yam, 10-15 parts of bighead atractylodes rhizome, 5-15 parts of coptis chinensis, 5-15 parts of medicinal cyathula root, 15-30 parts of rehmannia root, 5-15 parts of shizandra berry, 5-12 parts of gentian, 10-20 parts of pinellia tuber, 5-15 parts of cape jasmine, 5-15 parts of tree peony bark, 10-15 parts of white paeony root and 20-30 parts of oyster;
further, the traditional Chinese medicine composition also comprises the following raw materials in parts by weight:
10-20 parts of ligusticum wallichii, 15-20 parts of gastrodia elata and 5-10 parts of liquorice;
Further, the traditional Chinese medicine composition comprises the following raw materials in parts by weight:
15-20 parts of wild jujube seed, 12-15 parts of Chinese yam, 10-15 parts of bighead atractylodes rhizome, 8-10 parts of coptis chinensis, 10-15 parts of medicinal cyathula root, 20-30 parts of rehmannia root, 8-12 parts of shizandra berry, 8-12 parts of gentian, 10-15 parts of pinellia tuber, 8-10 parts of cape jasmine, 5-10 parts of tree peony bark, 12-15 parts of white peony root, 25-30 parts of oyster, 10-15 parts of szechuan lovage rhizome, 18-20 parts of tall gastrodia tuber and 8-10 parts of liquorice;
Further, in the traditional Chinese medicine composition, the spina date seed is fried spina date seed, the Chinese yam is fried Chinese yam, the bighead atractylodes rhizome is fried white atractylodes rhizome, the rehmannia root is dried rehmannia root, the pinellia tuber is prepared pinellia tuber, and the white paeony root is fried white paeony root.
The invention provides a specific application of the traditional Chinese medicine composition, namely application of the traditional Chinese medicine composition in preparing a medicine for treating headache.
A Chinese medicinal preparation is prepared from the Chinese medicinal composition.
Furthermore, the traditional Chinese medicine preparation can be clinically common dosage forms such as granules, tablets, pills, powder, medicinal granules, oral liquid, capsules, syrup, mixture and the like or clinically common decoction.
The invention has the following beneficial effects:
1. In the traditional Chinese medicine composition, dried rehmannia root, radix rehmanniae is used as a monarch drug for nourishing yin and cooling blood; rhizoma Dioscoreae has effects of invigorating qi, nourishing yin, invigorating spleen, invigorating kidney, atractylodis rhizoma has effects of invigorating spleen, invigorating qi, relieving pain, radix Paeoniae alba has effects of suppressing liver yang, nourishing blood, astringing yin, softening liver, relieving pain, cortex moutan has effects of clearing heat, cooling blood, promoting blood circulation, fructus Schisandrae astringing, invigorating kidney, calming heart, semen Ziziphi Spinosae has effects of nourishing heart, tranquilizing mind, and Concha Ostreae has effects of suppressing yang, astringing yin, suppressing hyperactive liver, and relieving pain; with the assistance of coptis chinensis, gardenia and gentian, the heat-clearing and fire-reducing effects are achieved; the pinellia tuber has the effects of relieving distension and fullness, resolving masses, activating blood and relieving pain, and guiding blood downwards, is a guiding medicine, and is used for treating various types of headache by mutually matching all the medicines together, and has the effects of nourishing yin, reducing pathogenic fire, suppressing hyperactive liver and suppressing yang.
2. The traditional Chinese medicine composition is a clinical laboratory recipe in the medical department, has a good treatment effect on various types of headaches caused by intermittent headaches, exogenous pathogenic wind, perimenopausal headaches and the like, and causes the headaches to be from the patient's mousse.
3. Pharmacological experiments prove that the traditional Chinese medicine composition has better analgesic effect and can effectively relieve pain symptoms of model mice.
Drawings
Fig. 1: the mice tenderness threshold in test 1, where x represents P <0.05 compared to the control group.
Fig. 2: rat behavioural scores in trial 2, where x represents P < 0.01 compared to the model group.
Fig. 3: the mechanical pain threshold of rats in trial 2, where x represents P < 0.05 compared to the model group.
Detailed Description
The present application is further illustrated below with reference to specific examples, which are to be construed as merely illustrative of the application and not limiting of its scope, as various equivalent modifications to the application will fall within the scope of the claims after reading the application.
Example 1 preparation of granules
Decocting semen Ziziphi Spinosae 20g, rhizoma Dioscoreae 15g, atractylodis rhizoma 12g, coptidis rhizoma 10g, radix Cyathulae 12g, rehmanniae radix 20g, fructus Schisandrae 10g, radix Gentianae 10g, rhizoma Pinelliae 12g, fructus Gardeniae 10g, cortex moutan 10g, radix Paeoniae alba 15g, concha Ostreae 30g, rhizoma Ligustici Chuanxiong 15g, rhizoma Gastrodiae 20g, and Glycyrrhrizae radix 10g with water for 2 times each for 1 hr, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to obtain fluid extract with relative density of 1.15-1.20 (50deg.C), adding appropriate amount of dextrin and sucrose, mixing, granulating, and drying to obtain granule.
Example 2 preparation of capsules
Decocting semen Ziziphi Spinosae 15g, rhizoma Dioscoreae 15g, atractylodis rhizoma 12g, coptidis rhizoma 8g, radix Cyathulae 12g, rehmanniae radix 30g, fructus Schisandrae 10g, radix Gentianae 10g, rhizoma Pinelliae 12g, fructus Gardeniae 10g, cortex moutan 10g, radix Paeoniae alba 15g, concha Ostreae 30g, rhizoma Ligustici Chuanxiong 10g, rhizoma Gastrodiae 18g, and Glycyrrhrizae radix 8 with water for 2 times each for 1 hr, mixing decoctions, filtering, concentrating the filtrate to soft extract with relative density of 1.10-1.20 (50deg.C), adding appropriate amount of starch, mixing, drying, pulverizing into fine powder, and making into capsule;
Example 3 tablet preparation
Decocting semen Ziziphi Spinosae 15g, rhizoma Dioscoreae 12g, atractylodis rhizoma 12g, coptidis rhizoma 10g, radix Cyathulae 15g, rehmanniae radix 30g, fructus Schisandrae 10g, radix Gentianae 10g, rhizoma Pinelliae 12g, fructus Gardeniae 10g, cortex moutan 10g, radix Paeoniae alba 15g, concha Ostreae 30g, rhizoma Ligustici Chuanxiong 15g, rhizoma Gastrodiae 20g, and Glycyrrhrizae radix 10g with water for 2 times each for 1 hr, mixing decoctions, filtering, concentrating the filtrate into soft extract with relative density of 1.20-1.25 (50deg.C), drying, pulverizing, sieving, making paste with starch, granulating, drying, adding microcrystalline cellulose, mixing, and tabletting to obtain tablet.
EXAMPLE 4 syrup preparation
Decocting semen Ziziphi Spinosae 15g, rhizoma Dioscoreae 15g, atractylodis rhizoma 10g, coptidis rhizoma 10g, radix Cyathulae 10g, rehmanniae radix 30g, fructus Schisandrae 8g, radix Gentianae 12g, rhizoma Pinelliae 10g, fructus Gardeniae 8g, cortex moutan 5g, radix Paeoniae alba 12g, concha Ostreae 25g with water for 2 times each time for 1 hr, mixing decoctions, filtering, concentrating filtrate to appropriate amount, adding sucrose, ethylparaben and sodium benzoate, boiling to dissolve, adding water to appropriate volume, stirring, filtering, and packaging to obtain syrup.
Example 5 preparation of oral liquid
Decocting 20g of wild jujube seed, 12g of Chinese yam, 15g of bighead atractylodes rhizome, 8g of coptis chinensis, 10g of medicinal cyathula root, 20g of rehmannia root, 12g of Chinese magnoliavine fruit, 8g of gentian, 15g of pinellia tuber, 8g of gardenia, 5g of tree peony bark, 12g of white paeony root and 25g of oyster with water for 2 times each time for 1 hour, merging decoction, filtering, concentrating filtrate to a proper amount, adding single syrup and potassium sorbate, heating to dissolve, refrigerating, filtering, adding water to a proper amount, stirring, filling and sterilizing to obtain the oral liquid.
Example 6 tablet preparation
Decocting semen Ziziphi Spinosae 15g, rhizoma Dioscoreae 20g, atractylodis rhizoma 10g, coptidis rhizoma 15g, radix Cyathulae 5g, rehmanniae radix 30g, fructus Schisandrae 5g, radix Gentianae 12g, rhizoma Pinelliae 20g, fructus Gardeniae 5g, cortex moutan 15g, radix Paeoniae alba 10g, concha Ostreae 30g, rhizoma Ligustici Chuanxiong 10g, rhizoma Gastrodiae 20g, and Glycyrrhrizae radix 5g with water for 2 times each for 1 hr, mixing decoctions, filtering, concentrating the filtrate to soft extract with relative density of 1.30-1.35 (50deg.C), adding microcrystalline cellulose and magnesium stearate, mixing, tabletting, and sugar coating to obtain tablet;
example 7 preparation of granules
Decocting semen Ziziphi Spinosae 25g, rhizoma Dioscoreae 10g, atractylodis rhizoma 15g, coptidis rhizoma 5g, radix Cyathulae 15g, rehmanniae radix 15g, fructus Schisandrae 15g, radix Gentianae 5g, rhizoma Pinelliae 10g, fructus Gardeniae 15g, cortex moutan 5g, radix Paeoniae alba 15g, concha Ostreae 20g, rhizoma Ligustici Chuanxiong 20g, rhizoma Gastrodiae 15g, and Glycyrrhrizae radix 10g with water for 2 times each for 1 hr, mixing decoctions, filtering, concentrating the filtrate to obtain fluid extract with relative density of 1.18-1.23 (50deg.C), adding sucrose and dextrin, and granulating to obtain granule.
2. Description of clinical application
The traditional Chinese medicine composition provided by the invention is a medical diagnosis and treatment medicine with characteristics of the hospital, has excellent effects in treating various types of headache caused by various reasons, and is exemplified by partial cases.
Case 1, zheng Mou, female, 32 years old, a wrinkled city person, a patient complains about intermittent headache, becomes heavies or gets worse when getting in the wind, sleep bad, dry mouth and bitter taste. The following formula: 20g of fried spina date seed, 15g of fried Chinese yam, 12g of fried bighead atractylodes rhizome, 10g of coptis chinensis, 12g of medicinal cyathula root, 20g of dried rehmannia root, 10g of shizandra berry, 10g of gentian, 12g of prepared pinellia tuber, 10g of fried gardenia, 10g of tree peony bark, 15g of fried white peony root and 30g of oyster, 7 pairs of the Chinese medicinal materials are taken, and decocted into decoction by water, one dose is taken twice a day in the morning and evening, 4 doses of Chinese medicinal materials are taken by patients, the sleep quality of the patients is obviously improved after feedback, the headache symptoms are relieved, and the patients feel no sensation when the patients feel on days or blowing.
Case 2, zhang Mou, women, 32 years old, juxian County, patients complain about intermittent headache, pain is untimely, oral ibuprofen can be relieved, but can not be healed. The following formula: 15g of fried spina date seed, 15g of fried Chinese yam, 12g of fried bighead atractylodes rhizome, 8g of coptis chinensis, 12g of medicinal cyathula root, 30g of dried rehmannia root, 10g of shizandra berry, 10g of tree peony bark, 12g of prepared pinellia tuber, 10g of fried gardenia, 15g of fried white paeony root, 10g of gentian and 30g of oyster, and the Chinese medicinal composition is decocted with water, taken one dose a day in the morning and evening, and taken by a patient for 5 doses of Chinese medicaments for return visit, and the patient heals without attack until now.
Case 3, li Mou, women, 44 years old, people in all cities, patients complain about headache, pain stops at time, irregular, and headache is aggravated during menstruation. The following formula: 15g of fried spina date seed, 12g of fried Chinese yam, 12g of fried bighead atractylodes rhizome, 10g of coptis chinensis, 15g of medicinal cyathula root, 30g of dried rehmannia root, 10g of shizandra berry, 10g of tree peony bark, 12g of prepared pinellia tuber, 10g of fried gardenia, 15g of fried white paeony root, 10g of gentian, 30g of oyster, 15g of szechuan lovage rhizome, 20g of tall gastrodia tuber and 10g of liquorice, and the Chinese medicinal preparation is decocted with water, and is taken twice a day in the morning and evening, and the symptoms of headache are completely disappeared from the moment of the re-diagnosis of the breast diseases of a patient, and the symptoms of dizziness and headache do not appear in the recent menstruation.
3. Pharmacological experiments
In order to further explore the treatment mechanism of the traditional Chinese medicine composition, relevant experiments are carried out on the analgesic effect of the traditional Chinese medicine composition by the relevant Cooperation units of the Ben special commission.
Before pharmacological experiments, the traditional Chinese medicine composition is subjected to acute toxicity experiments and long-term toxicity experiments, and the traditional Chinese medicine composition has safety, and the administration dosage in the following experiments is within a safe dosage range.
Test 1 analgesic effect of the Chinese medicinal composition of the present invention on mice
1 Material
1.1 Animals
Kunming mice, body weight 18-22g, license number: SYXK (robust) 20220029, was adapted for one week prior to the experiment.
1.2 Medicaments
Drug 1:20 g of fried spina date seed, 15g of fried Chinese yam, 12g of fried bighead atractylodes rhizome, 10g of coptis chinensis, 12g of medicinal cyathula root, 20g of radix rehmanniae, 10g of shizandra berry, 10g of gentian, 12g of prepared pinellia tuber, 10g of fried gardenia, 10g of tree peony bark, 15g of fried white peony root and 30g of oyster, adding water for decoction, filtering and concentrating to 200mL.
Drug 2: 15g of fried spina date seed, 15g of fried Chinese yam, 12g of fried bighead atractylodes rhizome, 8g of coptis chinensis, 12g of medicinal cyathula root, 30g of radix rehmanniae, 10g of shizandra berry, 10g of gentian, 12g of prepared pinellia tuber, 10g of fried gardenia, 10g of tree peony bark, 15g of fried white peony root and 30g of oyster, adding water for decoction, filtering and concentrating to 200mL.
Drug 3: 15g of fried spina date seed, 12g of fried Chinese yam, 12g of fried bighead atractylodes rhizome, 10g of coptis chinensis, 15g of medicinal cyathula root, 30g of radix rehmanniae, 10g of shizandra berry, 10g of gentian, 12g of prepared pinellia tuber, 10g of fried gardenia, 10g of tree peony bark, 15g of fried white peony root, 30g of oyster, 15g of szechuan lovage rhizome, 20g of tall gastrodia tuber and 10g of liquorice, decocting in water, filtering and concentrating to 200mL.
The equivalent dose of the mice is calculated according to the body surface area between the mice and the human in the pharmacology experimental methodology, namely the administration dose of the mice is as follows: 26mL/kg.
2 Experimental procedure
The following experiments were performed with reference to the prior art.
The mice were randomly divided into control group, experiment 1 group, experiment 2 group and experiment 3 group, and the administration was continued for 10 days by administering the same amount of distilled water according to the administration dose of the drugs 1, experiment 2 group, experiment 3 group, and experiment 3 group.
The mice are placed in a fixed cage after the last administration for 30min, the tail is exposed, the pressure position of the tail is adjusted, the pressure is gradually increased by a pain pressing instrument, and when the tail of the mice is pressed and painful (index is limb disorder or paw withdrawal, whole body shrinkage shaking), the pressure is stopped, and the pressed weight is the pain threshold.
All data were taken as mean ± standard deviationRepresenting metering data, processing by using SPSS22.0 statistical software, and adopting independent sample t test between two independent samples.
3 Experimental results and analysis
Before administration, the pain threshold of the mice in the experiment 1-3 groups is not obviously different from that of the mice in the control group (P is more than 0.05); after administration, the pain threshold of mice in the experiment 1-3 groups is obviously higher than that of the mice in the control group, and the mice show remarkable difference (P is less than 0.05), so that the traditional Chinese medicine composition has better pain relieving effect. The results are shown in FIG. 1.
Experiment 2 therapeutic Effect of the Chinese medicinal composition of the present invention on chronic migraine model rats
1 Material
SD rats, weight 180-220g, license number: SYXK (robust) 20220029, was adapted for one week prior to the experiment.
1.2 Medicaments
Drug 1:20 g of fried spina date seed, 15g of fried Chinese yam, 12g of fried bighead atractylodes rhizome, 10g of coptis chinensis, 12g of medicinal cyathula root, 20g of radix rehmanniae, 10g of shizandra berry, 10g of gentian, 12g of prepared pinellia tuber, 10g of fried gardenia, 10g of tree peony bark, 15g of fried white peony root and 30g of oyster, adding water for decoction, filtering and concentrating to 200mL.
Drug 2: 15g of fried spina date seed, 15g of fried Chinese yam, 12g of fried bighead atractylodes rhizome, 8g of coptis chinensis, 12g of medicinal cyathula root, 30g of radix rehmanniae, 10g of shizandra berry, 10g of gentian, 12g of prepared pinellia tuber, 10g of fried gardenia, 10g of tree peony bark, 15g of fried white peony root and 30g of oyster, adding water for decoction, filtering and concentrating to 200mL.
Drug 3: 15g of fried spina date seed, 12g of fried Chinese yam, 12g of fried bighead atractylodes rhizome, 10g of coptis chinensis, 15g of medicinal cyathula root, 30g of radix rehmanniae, 10g of shizandra berry, 10g of gentian, 12g of prepared pinellia tuber, 10g of fried gardenia, 10g of tree peony bark, 15g of fried white peony root, 30g of oyster, 15g of szechuan lovage rhizome, 20g of tall gastrodia tuber and 10g of liquorice, decocting in water, filtering and concentrating to 200mL.
The equivalent dosage of the rat is calculated according to the body surface area between the rat and the human in the pharmacological experiment methodology, namely the administration dosage of the rat is as follows: 18mL/kg.
2 Experimental procedure
The following experiments were performed with reference to the prior art.
The mice were randomly divided into a control group, a model group, an experiment 1 group, an experiment 2 group and an experiment 3 group, and the administration of the same amount of distilled water was continued for 30 days according to the administration doses, namely, the experiment 1 group was administered with the medicine 1, the experiment 2 group was administered with the medicine 2, the experiment 3 group was administered with the medicine 3, and the control group and the model group were administered with the medicine 3.
During the administration period, on days 10, 20 and 30, the rats in the model group and the rats in the experiments 1 to 3 were subcutaneously injected with nitroglycerin (10 mg/kg) in the nape of the human body 1 hour after the administration, and a chronic migraine model was established, and the rats in the control group were subcutaneously injected with an equal amount of physiological saline.
3 Observation index
3.1 Pain behavior scoring in rats
On days 10, 20 and 30, the behavior change of each group of rats after the completion of subcutaneous injection was observed, and whether the phenomena of earred, forelimbs scratch one's head, cage climbing (forelimb cage grasping cover) and the like occurred within 1h of injection were recorded, and pain behavior scoring was performed.
The times of the front limb scratch one's head reach 10 times, 1 minute is counted, and 0.1 minute is accumulated for each time;
The number of times of climbing the cage reaches 3 times, 1 minute is counted, and 1 minute is accumulated for each time;
Performing transfer in the cage for 2 times to count 1 minute, and accumulating 1 minute each time;
Counting 1 minute each time the tail is bitten;
the ear redness was counted 1 minute.
3.2 Rat pain threshold detection
Before the experiment, the basal mechanical pain threshold of each group of rats was determined, and after subcutaneous injection for 2 hours on days 10, 20, 30, respectively, the mechanical pain threshold of the sole of the foot was determined after each group of rats.
3.3 Statistical treatment
All data were taken as mean ± standard deviationRepresenting metering data, processing by using SPSS22.0 statistical software, and adopting independent sample t test between two independent samples.
4 Results and analysis
4.1 Pain behavioural changes in rats
During the experiment, rats in the control group have sensitive activities and luster of fur, no redness phenomenon occurs in ears during the pain behavioural measurement, and the behavioural score is less than 4 points; the model group rats have dull fur, and after being subcutaneously injected with nitroglycerin, the model group rats have pain symptoms such as reddening of ears, front limbs scratch one's head, climbing cage, tail biting, turning in the cage and the like, and the behavioural score is more than 15 minutes; rats in the experiment 1-3 groups have higher behavioural scores compared with rats in the control group, obviously lower behavioural scores compared with rats in the model group, and obviously relieve pain symptoms. The results are shown in FIG. 2.
4.2 Detection results of plantar pain threshold after rat
The basal mechanical pain threshold before each group of rats was not significantly different (P > 0.05); during the test, the mechanical pain threshold of the rats in the control group is basically unchanged, and the mechanical pain threshold of the rats in the model group shows a descending trend; the mechanical pain threshold of rats in experiments 1-3 showed a tendency to decrease and then increase. The results are shown in FIG. 3.
Claims (8)
1. A traditional Chinese medicine composition comprises the following raw materials in parts by weight:
15-25 parts of wild jujube seed, 10-20 parts of Chinese yam, 10-15 parts of bighead atractylodes rhizome, 5-15 parts of coptis chinensis, 5-15 parts of medicinal cyathula root, 15-30 parts of rehmannia root, 5-15 parts of shizandra berry, 5-12 parts of gentian, 10-20 parts of pinellia tuber, 5-15 parts of cape jasmine, 5-15 parts of tree peony bark, 10-15 parts of white paeony root and 20-30 parts of oyster.
2. The traditional Chinese medicine composition according to claim 1, further comprising the following raw materials in parts by weight:
10-20 parts of ligusticum wallichii, 15-20 parts of gastrodia elata and 5-10 parts of liquorice.
3. The traditional Chinese medicine composition according to claim 2, which comprises the following raw materials in parts by weight:
15-20 parts of wild jujube seed, 12-15 parts of Chinese yam, 10-15 parts of bighead atractylodes rhizome, 8-10 parts of coptis chinensis, 10-15 parts of medicinal cyathula root, 20-30 parts of rehmannia root, 8-12 parts of shizandra berry, 8-12 parts of gentian, 10-15 parts of pinellia tuber, 8-10 parts of cape jasmine, 5-10 parts of tree peony bark, 12-15 parts of white peony root, 25-30 parts of oyster, 10-15 parts of szechuan lovage rhizome, 18-20 parts of tall gastrodia tuber and 8-10 parts of liquorice.
4. The Chinese medicinal composition according to claim 3, wherein the semen Ziziphi Spinosae is parched semen Ziziphi Spinosae, rhizoma Dioscoreae is parched rhizoma Dioscoreae, atractylodis rhizoma is parched Atractylodis rhizoma, rehmanniae radix is radix rehmanniae, rhizoma Pinelliae is rhizoma Pinelliae Preparata, and radix Paeoniae alba is parched radix Paeoniae alba.
5. Use of a traditional Chinese medicine composition according to any one of claims 1-4 for the preparation of a medicament for the treatment of headache.
6. The use according to claim 5, wherein the headache is a primary headache or a secondary headache.
7. A Chinese medicinal preparation, which is characterized in that the Chinese medicinal preparation is prepared from the Chinese medicinal composition according to any one of claims 1 to 4.
8. The Chinese medicinal preparation according to claim 7, wherein the Chinese medicinal preparation is one or more of granule, tablet, pill, powder, granule, oral liquid, capsule, syrup, mixture, or clinically usual decoction.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202410247229.9A CN118286356A (en) | 2024-03-05 | 2024-03-05 | Traditional Chinese medicine composition for treating headache and application thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202410247229.9A CN118286356A (en) | 2024-03-05 | 2024-03-05 | Traditional Chinese medicine composition for treating headache and application thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN118286356A true CN118286356A (en) | 2024-07-05 |
Family
ID=91683713
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202410247229.9A Pending CN118286356A (en) | 2024-03-05 | 2024-03-05 | Traditional Chinese medicine composition for treating headache and application thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN118286356A (en) |
-
2024
- 2024-03-05 CN CN202410247229.9A patent/CN118286356A/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2012027882A1 (en) | Pharmaceutical composition for treating insomnia and preparation method thereof | |
CN1857690A (en) | Gynecopathy treating preparation and its preparing process | |
CN113995788B (en) | Liver protection composition and preparation process thereof | |
CN101396542B (en) | Traditional Chinese medicine formulation for treating gastrosis and preparation method thereof | |
CN107648479B (en) | Traditional Chinese medicine formula for treating hypertension and product thereof | |
CN102885975A (en) | Traditional Chinese medicine composition for treating diabetes mellitus | |
CN115350256B (en) | Traditional Chinese medicine composition for treating insomnia and preparation method thereof | |
CN105456818A (en) | Traditional Chinese medicine composition containing folium artemisiae argyi and being capable of treating insomnia and preparation method of traditional Chinese medicine composition | |
CN114224998B (en) | Traditional Chinese medicine composition, preparation and application for treating spleen-kidney yang deficiency type functional dyspepsia | |
CN111375035A (en) | Preparation and application of enteric-coated preparation for treating cervical spondylosis | |
CN118286356A (en) | Traditional Chinese medicine composition for treating headache and application thereof | |
CN108186821B (en) | Traditional Chinese medicine composition for treating nervous headache and preparation method and application thereof | |
CN113521167A (en) | Traditional Chinese medicine composition for Parkinson's disease and application thereof | |
CN111419946A (en) | Medicine for treating infertility and preparation method thereof | |
JPH01246224A (en) | Remedy for dementia | |
CN114848724B (en) | Traditional Chinese medicine composition for treating migraine and preparation method thereof | |
CN104337898B (en) | A kind of Chinese medicine composition of the treatment gout containing Semen Pruni | |
CN116211924B (en) | Application of traditional Chinese medicine composition in preparation of medicine for treating neuritis | |
CN116173152B (en) | Application of Mailuo Shutong preparation in preparing medicine for preventing and treating diabetic neuropathy | |
CN115282235B (en) | Chinese medicinal compound and compound granule for clearing heat and detoxicating, and preparation method thereof | |
CN115154535B (en) | Traditional Chinese medicine compound for improving atherosclerosis and preparation method thereof | |
CN108175818B (en) | Traditional Chinese medicine composition for treating glaucoma and preparation method and application thereof | |
CN106511881B (en) | A Chinese medicinal composition for invigorating kidney and preventing miscarriage, and its preparation method | |
CN108210588A (en) | A kind of pharmaceutical composition and preparation method with tranquilizing effect | |
CN117815345A (en) | Chinese medicinal composition with antidepressant, anxiolytic, antifatigue and sleep improving effects, and its preparation method |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination |