CN112057501B - 用于治疗肌肉萎缩与肌无力的中药组合物、中药药膏及外用热敷膏药贴 - Google Patents
用于治疗肌肉萎缩与肌无力的中药组合物、中药药膏及外用热敷膏药贴 Download PDFInfo
- Publication number
- CN112057501B CN112057501B CN202011137742.0A CN202011137742A CN112057501B CN 112057501 B CN112057501 B CN 112057501B CN 202011137742 A CN202011137742 A CN 202011137742A CN 112057501 B CN112057501 B CN 112057501B
- Authority
- CN
- China
- Prior art keywords
- parts
- chinese medicine
- traditional chinese
- myasthenia
- plaster
- 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.)
- Active
Links
- 239000003814 drug Substances 0.000 title claims abstract description 50
- 206010028372 Muscular weakness Diseases 0.000 title claims abstract description 44
- 239000011505 plaster Substances 0.000 title claims abstract description 30
- 239000002674 ointment Substances 0.000 title claims abstract description 29
- 230000036473 myasthenia Effects 0.000 title claims abstract description 23
- 206010002027 Amyotrophy Diseases 0.000 title abstract description 17
- 239000000203 mixture Substances 0.000 title abstract description 8
- 235000006533 astragalus Nutrition 0.000 claims abstract description 10
- 238000010438 heat treatment Methods 0.000 claims abstract description 10
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims abstract description 9
- 235000003140 Panax quinquefolius Nutrition 0.000 claims abstract description 9
- 235000008434 ginseng Nutrition 0.000 claims abstract description 9
- 241001061264 Astragalus Species 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 210000004233 talus Anatomy 0.000 claims abstract description 8
- 241000132012 Atractylodes Species 0.000 claims abstract description 7
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims abstract description 7
- 244000303040 Glycyrrhiza glabra Species 0.000 claims abstract description 7
- 244000197580 Poria cocos Species 0.000 claims abstract description 7
- 235000008599 Poria cocos Nutrition 0.000 claims abstract description 7
- 244000042430 Rhodiola rosea Species 0.000 claims abstract description 7
- 235000003713 Rhodiola rosea Nutrition 0.000 claims abstract description 7
- 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 7
- 235000011477 liquorice Nutrition 0.000 claims abstract description 7
- 241000005787 Cistanche Species 0.000 claims abstract description 6
- 244000131316 Panax pseudoginseng Species 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 238000002791 soaking Methods 0.000 claims description 25
- 201000000585 muscular atrophy Diseases 0.000 claims description 21
- 239000007788 liquid Substances 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 10
- 239000004831 Hot glue Substances 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 238000010298 pulverizing process Methods 0.000 claims description 5
- 230000000699 topical effect Effects 0.000 claims 1
- 208000010428 Muscle Weakness Diseases 0.000 abstract description 21
- 229940079593 drug Drugs 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 15
- 208000019505 Deglutition disease Diseases 0.000 abstract description 6
- 241000411851 herbal medicine Species 0.000 abstract description 3
- 230000009471 action Effects 0.000 abstract description 2
- 239000008187 granular material Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 18
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 201000010099 disease Diseases 0.000 description 11
- 210000003205 muscle Anatomy 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 10
- 206010028289 Muscle atrophy Diseases 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 208000005264 motor neuron disease Diseases 0.000 description 9
- 210000000952 spleen Anatomy 0.000 description 9
- 210000001364 upper extremity Anatomy 0.000 description 9
- 241000208340 Araliaceae Species 0.000 description 8
- 208000026072 Motor neurone disease Diseases 0.000 description 8
- 230000020763 muscle atrophy Effects 0.000 description 7
- 206010028417 myasthenia gravis Diseases 0.000 description 7
- 230000001737 promoting effect Effects 0.000 description 7
- 238000005520 cutting process Methods 0.000 description 6
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 210000003141 lower extremity Anatomy 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 208000000059 Dyspnea Diseases 0.000 description 4
- 206010013975 Dyspnoeas Diseases 0.000 description 4
- 230000037444 atrophy Effects 0.000 description 4
- 210000003414 extremity Anatomy 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 208000027905 limb weakness Diseases 0.000 description 4
- 231100000861 limb weakness Toxicity 0.000 description 4
- 235000019605 sweet taste sensations Nutrition 0.000 description 4
- 208000004880 Polyuria Diseases 0.000 description 3
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 230000035619 diuresis Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- 229960004181 riluzole Drugs 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 238000005728 strengthening Methods 0.000 description 3
- 239000003440 toxic substance Substances 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 241000045403 Astragalus propinquus Species 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- 241000336291 Cistanche deserticola Species 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- 241000721047 Danaus plexippus Species 0.000 description 2
- 206010021118 Hypotonia Diseases 0.000 description 2
- 208000002720 Malnutrition Diseases 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 241001619461 Poria <basidiomycete fungus> Species 0.000 description 2
- 206010070833 Respiratory muscle weakness Diseases 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 235000019658 bitter taste Nutrition 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000002567 electromyography Methods 0.000 description 2
- 208000017561 flaccidity Diseases 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000001071 malnutrition Effects 0.000 description 2
- 235000000824 malnutrition Nutrition 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 208000015380 nutritional deficiency disease Diseases 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 235000019640 taste Nutrition 0.000 description 2
- 230000002936 tranquilizing effect Effects 0.000 description 2
- VHRSUDSXCMQTMA-PJHHCJLFSA-N 6alpha-methylprednisolone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 VHRSUDSXCMQTMA-PJHHCJLFSA-N 0.000 description 1
- 206010000234 Abortion spontaneous Diseases 0.000 description 1
- 241000208838 Asteraceae Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 241000336315 Cistanche salsa Species 0.000 description 1
- 241000336316 Cistanche tubulosa Species 0.000 description 1
- 206010010264 Condition aggravated Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241000220284 Crassulaceae Species 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 101100082305 Drosophila melanogaster Panx gene Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 241000220485 Fabaceae Species 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 206010062758 Myasthenia gravis crisis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000017787 Paraneoplastic neurologic syndrome Diseases 0.000 description 1
- 241000222341 Polyporaceae Species 0.000 description 1
- 241001165494 Rhodiola Species 0.000 description 1
- 241000997135 Rhodiola crenulata Species 0.000 description 1
- 241001558929 Sclerotium <basidiomycota> Species 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000000728 Thymus Neoplasms Diseases 0.000 description 1
- 208000031975 Yang Deficiency Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001166 anti-perspirative effect Effects 0.000 description 1
- 239000003213 antiperspirant Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000001914 calming effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000001097 facial muscle Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 229940106977 lansoprazole 30 mg Drugs 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 210000003784 masticatory muscle Anatomy 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 208000015994 miscarriage Diseases 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 210000004237 neck muscle Anatomy 0.000 description 1
- 208000029522 neoplastic syndrome Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001703 neuroimmune Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000003405 preventing effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000019643 salty taste Nutrition 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000005982 spleen dysfunction Effects 0.000 description 1
- 208000000995 spontaneous abortion Diseases 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
- A61K36/076—Poria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/284—Atractylodes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/41—Crassulaceae (Stonecrop family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/64—Orobanchaceae (Broom-rape family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Botany (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种用于治疗肌肉萎缩与肌无力的中药组合物、中药药膏及外用热敷膏药贴,属于医药技术领域。本发明的中药组合物按质量份数计,原料包括以下组分:人参8‑12份,黄芪28‑32份,肉苁蓉14‑16份,白术8‑12份,茯苓8‑12份,甘草8‑12份,红景天8‑12份。本发明选取七味有效中草药,经过萃取制成膏药制剂,通过外层添加发热颗粒剂制成发热贴,直接贴于患者背部,克服了肌无力和肌肉萎缩患者吞咽困难导致影响药物发挥作用的问题,减轻了患者痛苦,对于肌无力和肌萎缩的治疗疗效显著,对皮肤无刺激、安全性高,具有重要的临床应用价值。
Description
技术领域
本发明涉及医药技术领域,特别是涉及用于治疗肌肉萎缩与肌无力的中药组合物、中药药膏及外用热敷膏药贴。
背景技术
肌无力与肌肉萎缩是神经科慢性疾病的常见症状,特别是一些神经科变性疾病。
运动神经元病(MND)/肌萎缩侧索硬化症(ALS)呈现出慢性进展性四肢与躯干肌肉的无力与萎缩,晚期颜面肌肉、舌肌与咀嚼肌、胸锁乳突肌等肌肉的无力与萎缩,最终患者因为呼吸困难、无法进食、严重营养不良以及感染等因素死亡。目前为止,除了一些可能有效的药物如力如太(利鲁唑)可以部分延缓一少部分患者的疾病的进展(与安慰剂比较可以延缓疾病进展数月),患者有效生存期一般为2-5年(潘卫东,苏小静,王骏,秦保锋,吴春岚,朱金,蔡定芳.健脾益气法治疗肌萎缩侧索硬化症的随机开放临床试验[J].上海中医药大学学报,2013,(03):38-41)。
还有一些以发作性或持续性肌肉无力为主要症状的神经科疾病,如重症肌无力(MG),也是危害患者生活治疗与生命健康的重要疾病,以眼肌或四肢肌肉无力为主,在一些特定的情况下会出现严重的肌无力,影响呼吸机功能而出现重症肌无力危象可危机生命(李柱一,张巍.重症肌无力发病机制和治疗的回顾与展望[J].中国现代神经疾病杂志,2012,(02):113-116)。
另一类肌无力疾病是神经系统副肿瘤综合症既可以周围神经肌肉改变,也可以出现中枢神经系统,属于自身免疫性疾病,上肢肌肉与呼吸肌无力为常见症状。目前中医对于这一类疾病治疗使用口服健脾、益气、补肾药物,在一定程度上有一定疗效(Pan W,Su X,Bao J,Wang J,et al.Open Randomized Clinical Trial on JWSJZ Decoction for theTreatment of ALS Patients[J].Evidence-based Complementary and AlternativeMedicine,vol.2013,Article ID 347525,5pages,doi:10.1155/2013/347525;暴洁,陈向军,潘卫东,白宇,吕桦,王厹东,刘毅,袁灿兴,李文伟,刘振国,刘军,秦保锋.上海地区肌萎缩侧索硬化症患者接受综合治疗现状分析[J].上海中医药大学学报,2014,(02):17-22),但是这一类患者大都在疾病加重时期出现吞咽困难,甚至严重的恶心、呕吐,无法口服药物,不能发挥中药疗效。
MND/ALS为脊髓前角细胞为主的神经变性疾病,而MG也常常是由于胸腺肿瘤或胸部相关疾病引起的神经免疫性疾病,而神经系统副肿瘤综合症也与肺部或胸部肿瘤相关,支配相关肌肉的神经多发自于颈髓与胸髓。此类慢性的肌无力与肌萎缩疾病在中医多属于痿证(痿病),认为有先天或后天因素引起的脾肾阳虚、脾失健运、肝失疏泄所导致,发病原因有先天不足,有后天失养(损耗过度),也有湿热等原因,但以肝脾肾亏虚为主(潘卫东.基于健脾疏肝补益肝肾论神经变性疾病的辨治[J].上海中医药大学学报,2019,(02):1-6+31)。
针对肌无力与肌肉萎缩症状的特殊性,提供一种疗效显著、使用方便的中药制剂对于肌无力和肌萎缩的临床治疗具有重要意义。
发明内容
本发明的目的是提供用于治疗肌肉萎缩与肌无力的中药组合物、中药药膏及外用热敷膏药贴,以解决上述现有技术存在的问题,以解决因患者吞咽困难导致无法服用药物的问题,并显著提升肌无力和肌萎缩的治疗疗效。
为实现上述目的,本发明提供了如下方案:
本发明的目的之一是提供一种用于治疗肌肉萎缩与肌无力的中药组合物,按质量份计,原料包括以下组分:
人参8-12份,黄芪28-32份,肉苁蓉14-16份,白术8-12份,茯苓8-12份,甘草8-12份,红景天8-12份。
本发明的目的之二是提供一种用于治疗肌肉萎缩与肌无力的中药药膏,包括上述中药组合物。
本发明的目的之三是提供一种上述用于治疗肌肉萎缩与肌无力的中药药膏的制备方法,包括以下步骤:
(1)将原料混合,粉碎,用乙醇浸渍提取,过滤,得浸渍液;
(2)回收浸渍液中的乙醇,然后将浸渍液浓缩,得浓缩浸渍液;
(3)将熔化的热熔胶与浓缩浸渍液混合,得到所述中药药膏。
进一步地,步骤(1)中所述浸渍提取时间为6-8天。
进一步地,步骤(2)中所述浓缩浸渍液的相对密度为1.35-1.45。
其中,步骤(2)在回收浸渍液中的乙醇时,首先利用沸点不同,通过蒸发浓缩回收乙醇,达到浸渍液所需相对密度,然后采用真空干燥将剩余乙醇分离;浸渍液的浓缩方式采用行业内常规中药膏剂浓缩方式,不会影响本发明中药药膏的疗效,浓缩方式在此不再赘述。
本发明的目的之四是提供一种用于治疗肌肉萎缩与肌无力的外用热敷膏药贴,包括上述中药药膏及发热贴。
本发明公开了以下技术效果:
本发明选取七味有效中草药,其中人参与黄芪共为君药:人参为五加科人参的干燥根与根茎,味甘、微苦,性微温,归脾、肺、心、肾经,具有大补元气、复脉固脱、补脾益肺、生津养血、安神益智作用,在此配方中为君药;黄芪为豆科植物蒙古黄芪的干燥根,味甘,微温,归脾、肺经,具有补气升阳、益卫固表、利水消肿、生津养血、行滞通弊、拖毒排脓、敛疮生肌作用;臣药为肉苁蓉、白术以及茯苓:肉苁蓉为列当科植物肉苁蓉或管花肉苁蓉(本申请使用)的干燥带鳞叶的肉质茎,味甘、咸,性温,归肾、大肠经,具有补肾阳、益精血、润肠通便作用;白术为菊科植物白术的干燥茎根,味甘、苦,性温,归脾、胃经,具有补气健脾、燥湿利水、止汗、安胎作用;茯苓为多孔菌科真菌茯苓的干燥菌核,味甘、淡,性平,归心、肺、脾、肾经,具有利水胜湿、健脾、宁心安神的作用;甘草与红景天共为佐使药:甘草为豆科植物甘草的干燥根和根茎,味甘,性平,归心、肺、脾、胃经,具有补脾益气、清热解毒、祛痰止咳、缓急止痛、调和诸药的作用;红景天为景天科植物大花红景天的干燥根和根茎,味甘、苦,性平,归肺、脾、心经,具有益气活血、通脉平喘的作用。整个配方具有大补元气、行经通络、生精血、去湿毒作用,补益而不滋腻、解毒祛湿而不伤正气的作用。
本发明将上述中草药经过萃取制成膏药制剂,通过外层添加发热颗粒剂制成发热贴,直接贴于患者背部,本发明药物作用时间可以持续12-16h,对于肌无力和肌萎缩的治疗疗效显著。
肌无力和肌萎缩患者大都在疾病加重时期出现吞咽困难,甚至严重的恶心、呕吐,无法口服药物,从而导致药物无法发挥治疗作用,加重患者痛苦;本发明的发热贴可以直接贴在患者背部,克服了因患者吞咽困难影响药物作用的问题,减轻了患者痛苦,对皮肤无刺激、安全性高,具有重要的临床应用价值。
具体实施方式
现详细说明本发明的多种示例性实施方式,该详细说明不应认为是对本发明的限制,而应理解为是对本发明的某些方面、特性和实施方案的更详细的描述。
应理解本发明中所述的术语仅仅是为描述特别的实施方式,并非用于限制本发明。另外,对于本发明中的数值范围,应理解为还具体公开了该范围的上限和下限之间的每个中间值。在任何陈述值或陈述范围内的中间值以及任何其他陈述值或在所述范围内的中间值之间的每个较小的范围也包括在本发明内。这些较小范围的上限和下限可独立地包括或排除在范围内。
除非另有说明,否则本文使用的所有技术和科学术语具有本发明所述领域的常规技术人员通常理解的相同含义。虽然本发明仅描述了优选的方法和材料,但是在本发明的实施或测试中也可以使用与本文所述相似或等同的任何方法和材料。本说明书中提到的所有文献通过引用并入,用以公开和描述与所述文献相关的方法和/或材料。在与任何并入的文献冲突时,以本说明书的内容为准。
在不背离本发明的范围或精神的情况下,可对本发明说明书的具体实施方式做多种改进和变化,这对本领域技术人员而言是显而易见的。由本发明的说明书得到的其他实施方式对技术人员而言是显而易见得的。本申请说明书和实施例仅是示例性的。
关于本文中所使用的“包含”、“包括”、“具有”、“含有”等等,均为开放性的用语,即意指包含但不限于。
本发明中所述的“份”如无特别说明,均按质量份计。
实施例1
一种用于治疗肌肉萎缩与肌无力的外用热敷膏药贴,以重量份计,原料包括以下组分:
人参10份,黄芪30份,肉苁蓉15份,白术10份,茯苓10份,甘草10份,红景天10份。
制备方法如下:
(1)将上述原料混合,粉碎成粗粉,用8倍75%乙醇浸渍提取8天,过滤,得浸渍液;
(2)回收浸渍液中的乙醇,20℃条件下,将除去乙醇的浸渍液浓缩至相对密度为1.45(膏量在粗粉重量的0.4倍),得浓缩后的浸渍液;
(3)在180℃下将热熔胶熔化,与浓缩后的浸渍液混合均匀,得到治疗肌肉萎缩与肌无力的药膏;
(4)将步骤(3)制备得到的药膏上机涂布分切,分切速度5m/min,然后与热敷贴结合,热敷贴背面为发热材料,密封包装即得。
实施例2
一种用于治疗肌肉萎缩与肌无力的外用热敷膏药贴,以重量份计,原料包括以下组分:
人参8份,黄芪32份,肉苁蓉14份,白术12份,茯苓8份,甘草12份,红景天12份。
制备方法如下:
(1)将上述原料混合,粉碎成粗粉,用10倍75%乙醇浸渍提取7天,过滤,得浸渍液;
(2)回收浸渍液中的乙醇,20℃条件下,将除去乙醇的浸渍液浓缩至相对密度为1.35(膏量在粗粉重量的0.3倍),得浓缩后的浸渍液;
(3)在180℃下将热熔胶熔化,与浓缩后的浸渍液混合均匀,得到治疗肌肉萎缩与肌无力的药膏;
(4)将步骤(3)制备得到的药膏上机涂布分切,分切速度5m/min,然后与热敷贴结合,热敷贴背面为发热材料,密封包装即得。
实施例3
一种用于治疗肌肉萎缩与肌无力的外用热敷膏药贴,以重量份计,原料包括以下组分:
人参12份,黄芪28份,肉苁蓉16份,白术8份,茯苓12份,甘草8份,红景天8份。
制备方法如下:
(1)将上述原料混合,粉碎成粗粉,用9倍75%乙醇浸渍提取6天,过滤,得浸渍液;
(2)回收浸渍液中的乙醇,20℃条件下,将除去乙醇的浸渍液浓缩至相对密度为1.4,得浓缩后的浸渍液;
(3)在180℃下将热熔胶熔化,与浓缩后的浸渍液混合均匀,得到治疗肌肉萎缩与肌无力的药膏;
(4)将步骤(3)制备得到的药膏上机涂布分切,分切速度5m/min,然后与热敷贴结合,热敷贴背面为发热材料,密封包装即得。
本发明的治疗肌肉萎缩与肌无力的外用热敷膏药贴的使用方法如下:
(1)贴敷部位
a.对于颈部肌肉与上肢肌肉萎缩或(和)肌无力患者:将中药膏药面(黑色)横向(长边垂直于脊柱方向)或纵向(短边垂直于脊柱方向)贴于大椎穴(第7颈椎棘突下凹陷中)向下面位置,延颈背部正中线向下方。
b.下肢肌无力或肌萎缩患者:将中药膏药面(黑色)横向(长边垂直于脊柱方向)贴于以肾腧穴位为中心的腰部皮肤(第二腰椎棘突旁开1.5寸处,腰椎两侧两只穴位)位置。
(2)贴敷时间与疗程:
贴敷12-16h;敷贴为一次性使用品,隔日使用一贴,14贴为一疗程;症状严重患者可每日敷贴。
本发明的治疗肌肉萎缩与肌无力的外用热敷膏药贴临床治疗实例:
1.肌萎缩侧索硬化症双上肢无力与吞咽困难患者治疗实例
患者潘X英,女性,54岁,上海籍。确诊运动神经元病3年,以右上肢无力发病逐渐发展至四肢无力,肌肉萎缩,近半年开始舌肌萎缩,言语含糊,饮水有呛咳,在本院经过三次肌电图检查明确广泛性神经源性损害而明确运动神经元病/肌萎缩侧索硬化症,服用利鲁唑半年无效,疾病渐进进展,停服利鲁唑,使用实施例1的热敷膏药贴,按照使用方法的(1)中的a部分使用,隔日一次,连续使用6周,双上肢肌无力没有进展,并且较前有改善,均能够短暂性抬举,手指也较前灵活,疗效维持,继续使用中,患者与家属均较为满意。
2.以下肢发病的MND/ALS的患者治疗实例
患者陈X儒,男性,48岁,福建籍。患者以右下肢肌无力发病渐进加重半年,双下肢渐进性肌无力与肌肉萎缩,来上海就诊前一月左右,右上肢也开始出现肌无力与肌萎缩症状,四肢肌肉跳动明显(束颤),在当地三甲医院与上海医院瑞金医院经多次肌电图检查,明确广泛性神经源性损害而明确运动神经元病/肌萎缩侧索硬化症。给予本发明实施例2的外用热敷膏药贴进行治疗,按照方法(1)中的b部分治疗,隔日外敷一次,患者双下肢肌力有所改善,肌肉萎缩亦有明显缓解,目前仍坚持采用药外用热敷膏药贴治疗,未发生明显皮疹、湿疹等不良反应。
3.重症肌无力(MG)眼肌无力与上肢无力患者治疗实例
患者倪XX,女,68岁,五年前因发作性呼吸困难、呼吸肌无力,在上海仁济医院发现有肺部占位性病变,考虑胸腺瘤,重症肌无力,给予手术切除胸腺瘤,激素以及溴吡斯的明口服治疗后缓解。三年前出现双眼肌无力、阵发平卧时呼吸肌无力在仁济医院神经内科诊断为MG,给予相似治疗激素与溴吡斯的明口服治疗,疗效不佳,随即转院至曙光医院东院神经内科,入院后复查胸部CT发现右侧肺部占位,但是患者与家属拒绝进一步检查其肺部症状,要求中西医结合治疗患者肌无力,入院后给予甲强龙(500mg),静脉滴注,每天1次;兰索拉唑30mg,静脉滴注,每天一次;黄芪注射液60ml,静脉滴注,每天1次;同时给予溴吡斯的明60mg,tid,口服,患者症状仍然较重,平卧时气急,呼吸困难,故停药;给予本发明实施例3的热敷膏药,按照敷贴方法中(1)的a方法敷贴,每天1次,治疗4天后,患者双眼肌抬举与平卧呼吸困难明显改善,继续治疗10天后出院。
4.运动神经元病/肌萎缩侧索硬化症(MND/ALS)治疗实例
使用本热敷膏药敷贴治疗在曙光医院神经内科(门诊与病房)治疗四肢肌肉无力与萎缩为主的MND/ALS患者12例。
将上述患者随机分成三组,分别使用本发明实施例1-3的外用热敷膏药贴,对应采用(1)中的a或b方法使用敷贴治疗一个疗程(14次为一个疗程)或一个疗程以上:
有效:肌无力或萎缩进展延缓或停止;肌无力或肌萎缩两种情况改善为有效;
无效:肌无力或肌萎缩进展速度无变化。
临床治疗结果:
12人中使用时间最短为2个疗程,有2人,3个疗程者4人,其余6人均使用4个疗程或以上;
有效者10人(83.33%),其中以上肢症状改善者居多(6/10),最明显的症状改善是热敷贴(大椎穴位)贴上至少10分钟后患者立刻感到双上肢力气增加,敷贴去掉后力气能够维持数小时,连续使用后自觉肌无力改善明显,肌肉萎缩亦有改善,肌肉跳动(束颤)也减少。未发现除皮肤局部刺激之外的不良反应。
以上所述的实施例仅是对本发明的优选方式进行描述,并非对本发明的范围进行限定,在不脱离本发明设计精神的前提下,本领域普通技术人员对本发明的技术方案做出的各种变形和改进,均应落入本发明权利要求书确定的保护范围内。
Claims (1)
1.一种用于治疗肌肉萎缩与肌无力的外用热敷膏药贴,其特征在于,包括中药药膏及发热贴;按质量份数计,所述中药药膏原料由以下组分组成:
人参8-12份,黄芪28-32份,肉苁蓉14-16份,白术8-12份,茯苓8-12份,甘草8-12份,红景天8-12份;
所述中药药膏的制备方法包括以下步骤:
(1)将原料混合,粉碎,用75%乙醇浸渍提取,过滤,得浸渍液;
(2)回收浸渍液中的乙醇,然后将浸渍液浓缩,得浓缩浸渍液;
(3)将熔化的热熔胶与浓缩浸渍液混合,得到所述中药药膏;
步骤(1)中所述浸渍提取时间为6-8天;
步骤(2)中所述浓缩浸渍液的相对密度为1.35-1.45。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011137742.0A CN112057501B (zh) | 2020-10-22 | 2020-10-22 | 用于治疗肌肉萎缩与肌无力的中药组合物、中药药膏及外用热敷膏药贴 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011137742.0A CN112057501B (zh) | 2020-10-22 | 2020-10-22 | 用于治疗肌肉萎缩与肌无力的中药组合物、中药药膏及外用热敷膏药贴 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112057501A CN112057501A (zh) | 2020-12-11 |
CN112057501B true CN112057501B (zh) | 2024-01-26 |
Family
ID=73655798
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011137742.0A Active CN112057501B (zh) | 2020-10-22 | 2020-10-22 | 用于治疗肌肉萎缩与肌无力的中药组合物、中药药膏及外用热敷膏药贴 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112057501B (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113694043B (zh) * | 2021-08-17 | 2023-12-22 | 西安电子科技大学 | 一种治疗肌肉萎缩的红景天苷贴剂 |
CN117982720B (zh) * | 2024-04-01 | 2024-06-04 | 成都中医药大学 | 一种预防损伤放松肌肉的中药材凝胶敷料及其制备方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101293043A (zh) * | 2007-04-24 | 2008-10-29 | 上海中医药大学附属曙光医院 | 一种治疗肌萎缩侧索硬化症的药物制剂及其制备方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101288478B (zh) * | 2008-05-28 | 2012-05-23 | 河北科技大学 | 可增强耐力的营养剂及其制备方法 |
CN105944031A (zh) * | 2016-06-28 | 2016-09-21 | 牡丹江医学院红旗医院 | 抗辐射中药及制作方法 |
-
2020
- 2020-10-22 CN CN202011137742.0A patent/CN112057501B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101293043A (zh) * | 2007-04-24 | 2008-10-29 | 上海中医药大学附属曙光医院 | 一种治疗肌萎缩侧索硬化症的药物制剂及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN112057501A (zh) | 2020-12-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103272169B (zh) | 一种红景天复方组合物在治疗糜烂性胃炎中的用途 | |
CN103285310B (zh) | 一种红景天复方组合物在制备治疗胃溃疡的药物中的用途 | |
CN102068682A (zh) | 一种治疗消化系统疾病的中药组合物及其制备方法 | |
CN112057501B (zh) | 用于治疗肌肉萎缩与肌无力的中药组合物、中药药膏及外用热敷膏药贴 | |
CN103285309A (zh) | 一种治疗消化性溃疡的红景天复方组合物 | |
CN104138550A (zh) | 一种治疗消化性溃疡药物的制备方法 | |
CN103272170B (zh) | 一种红景天复方组合物在制备治疗十二指肠溃疡的药物中的用途 | |
CN104001008A (zh) | 一种治疗肾虚髓亏证型脑鸣的中药组合物及其制备方法 | |
CN102579610A (zh) | 一种治疗脑出血的中药组合物及其制备方法 | |
CN101926903A (zh) | 用于治疗面神经麻痹的中药制剂 | |
CN112587596A (zh) | 一种治疗虚火痰结证淋巴系统疾病的药物组合物 | |
CN101579507B (zh) | 一种治疗胆结石的药物及其制备方法 | |
CN104138551A (zh) | 一种药物组合物在制备治疗十二指肠溃疡的药物中的用途 | |
CN108079113A (zh) | 一种治疗产后血虚的药物组合物及其制备方法 | |
CN110841007B (zh) | 一种治疗脑中风后遗症的中药组合物及其应用 | |
CN105327024A (zh) | 一种治疗类风湿性关节炎的中药制剂 | |
CN105456447A (zh) | 一种含有艾叶的具有活血化淤功能的中药组合物及其制备方法 | |
CN105582139B (zh) | 治疗脾肾气虚、气阴两虚型慢性肾功能衰竭的中药组合物及其制备方法 | |
CN105055852A (zh) | 一种治疗高血压的中药方剂 | |
CN104606426A (zh) | 一种治疗慢性胃炎的中药组合物制剂及其制备方法 | |
CN104096202A (zh) | 一种治疗秋季腹泻的药物及其制备方法 | |
CN104606377A (zh) | 一种治疗胃炎的中药组合物 | |
CN109288996A (zh) | 一种用于重症肌无力病症的中药组合物及其应用 | |
CN103768251B (zh) | 一种杀灭血液细胞中病毒、提高人体抗体免疫力的药物 | |
CN117442679A (zh) | 一种防治冠心病的参七药物组合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |