CN110339252B - 一种具有缓解非酒精性脂肪性肝炎的中药组合物及其制备方法和产品 - Google Patents
一种具有缓解非酒精性脂肪性肝炎的中药组合物及其制备方法和产品 Download PDFInfo
- Publication number
- CN110339252B CN110339252B CN201910632010.XA CN201910632010A CN110339252B CN 110339252 B CN110339252 B CN 110339252B CN 201910632010 A CN201910632010 A CN 201910632010A CN 110339252 B CN110339252 B CN 110339252B
- Authority
- CN
- China
- Prior art keywords
- liver
- chinese medicine
- traditional chinese
- medicine composition
- nash
- 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 61
- 239000000203 mixture Substances 0.000 title claims abstract description 49
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 title abstract description 51
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 title abstract description 42
- 238000002360 preparation method Methods 0.000 title abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 240000001659 Oldenlandia diffusa Species 0.000 claims abstract description 19
- 229940079593 drug Drugs 0.000 claims abstract description 15
- 235000003261 Artemisia vulgaris Nutrition 0.000 claims abstract description 14
- 235000009051 Ambrosia paniculata var. peruviana Nutrition 0.000 claims abstract description 13
- 235000003097 Artemisia absinthium Nutrition 0.000 claims abstract description 13
- 235000017731 Artemisia dracunculus ssp. dracunculus Nutrition 0.000 claims abstract description 13
- 239000001138 artemisia absinthium Substances 0.000 claims abstract description 13
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims abstract description 13
- 230000036541 health Effects 0.000 claims abstract description 7
- 241000316342 Taxillus Species 0.000 claims abstract description 4
- 240000001972 Gardenia jasminoides Species 0.000 claims abstract 4
- 238000000034 method Methods 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 11
- 240000001638 Scurrula parasitica Species 0.000 claims description 10
- 238000003809 water extraction Methods 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 8
- 239000012982 microporous membrane Substances 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 238000009835 boiling Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 235000013305 food Nutrition 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 241000092668 Artemisia capillaris Species 0.000 claims description 3
- 235000008658 Artemisia capillaris Nutrition 0.000 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- 244000269722 Thea sinensis Species 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 235000013402 health food Nutrition 0.000 claims 2
- 240000006891 Artemisia vulgaris Species 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 210000004185 liver Anatomy 0.000 abstract description 49
- 230000000694 effects Effects 0.000 abstract description 16
- 240000001851 Artemisia dracunculus Species 0.000 abstract description 12
- 238000002474 experimental method Methods 0.000 abstract description 6
- 238000009825 accumulation Methods 0.000 abstract description 5
- 150000002632 lipids Chemical class 0.000 abstract description 5
- 230000036285 pathological change Effects 0.000 abstract description 5
- 231100000915 pathological change Toxicity 0.000 abstract description 5
- 230000002757 inflammatory effect Effects 0.000 abstract description 4
- 230000008961 swelling Effects 0.000 abstract description 4
- 210000005228 liver tissue Anatomy 0.000 description 26
- 241000700159 Rattus Species 0.000 description 24
- 241000157835 Gardenia Species 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 239000008280 blood Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 9
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 238000007710 freezing Methods 0.000 description 6
- 230000008014 freezing Effects 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 208000004930 Fatty Liver Diseases 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 241000488974 Loranthus Species 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 231100000240 steatosis hepatitis Toxicity 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 206010019708 Hepatic steatosis Diseases 0.000 description 4
- 206010062717 Increased upper airway secretion Diseases 0.000 description 4
- 208000004880 Polyuria Diseases 0.000 description 4
- 230000035508 accumulation Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 208000019425 cirrhosis of liver Diseases 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 230000035619 diuresis Effects 0.000 description 4
- 208000010706 fatty liver disease Diseases 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 230000003071 parasitic effect Effects 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 208000026435 phlegm Diseases 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000006372 lipid accumulation Effects 0.000 description 3
- 208000018191 liver inflammation Diseases 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 238000010200 validation analysis Methods 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- 206010057573 Chronic hepatic failure Diseases 0.000 description 2
- 208000027534 Emotional disease Diseases 0.000 description 2
- 208000010334 End Stage Liver Disease Diseases 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000003777 Interleukin-1 beta Human genes 0.000 description 2
- 108090000193 Interleukin-1 beta Proteins 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 208000011444 chronic liver failure Diseases 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 210000000232 gallbladder Anatomy 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000003934 vacuole Anatomy 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 239000012224 working solution Substances 0.000 description 2
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 235000003826 Artemisia Nutrition 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 235000014066 European mistletoe Nutrition 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 240000000249 Morus alba Species 0.000 description 1
- 235000008708 Morus alba Nutrition 0.000 description 1
- 238000013231 NASH rodent model Methods 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 108010028924 PPAR alpha Proteins 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 206010033372 Pain and discomfort Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 244000152640 Rhipsalis cassutha Species 0.000 description 1
- 235000012300 Rhipsalis cassutha Nutrition 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 244000030166 artemisia Species 0.000 description 1
- 235000009052 artemisia Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000000841 delta opiate receptor agonist Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000512 lipotoxic effect Effects 0.000 description 1
- 238000012317 liver biopsy Methods 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000005163 right hepatic lobe Anatomy 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- 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)
-
- 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
- A61K36/282—Artemisia, e.g. wormwood or sagebrush
-
- 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)
- A61K36/74—Rubiaceae (Madder family)
- A61K36/744—Gardenia
-
- 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)
- A61K36/74—Rubiaceae (Madder family)
- A61K36/748—Oldenlandia or Hedyotis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- 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
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Botany (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Polymers & Plastics (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明公开了一种具有缓解非酒精性脂肪性肝炎的中药组合物及其制备方法和产品,该中药组合物包含的成分有茵陈、白花蛇舌草、栀子根、桑寄生,比例为1:0.8‑1.5:0.2‑1.2:0.2‑1.2,将上述成分水提后再浓缩,可得到上述的中药组合物。该中药组合物可制成保健品或药品,对于缓解非酒精性脂肪性肝炎具有重要功效。经实验证明,本发明中药组合物能够有效减轻肝脏的肿胀,改善肝脏病理变化,减少肝脏脂质蓄积,降低肝脏炎症因子水平,有效缓解NASH的功效。
Description
技术领域
本发明涉及药物领域,具体涉及一种具有缓解非酒精性脂肪性肝炎的中药组合物及其制备方法和产品。
背景技术
非酒精性脂肪性肝病(NAFLD)是一种代谢性肝病,以肝细胞内脂质沉积为特征并排除其他肝损害原因,其疾病谱包括非酒精性脂肪性肝炎(NASH)、纤维化、肝硬化和肝细胞癌。随着人们生活方式与饮食结构的改变,目前全球 NAFLD发病率已达到约25.24%,数据显示接受肝活检的NAFLD患者中约有59%的NALFD已发展为NASH。NASH是NAFLD的一个亚型,为肝脂肪变性与肝损伤和炎症共存,值得注意的是,NASH已成为肝移植的第二大常见适应症,是单纯性脂肪肝向肝硬化发展的必经阶段,也是肝细胞癌的第二大原因。NAFLD 被认为是一种多系统疾病,同时,NASH与2型糖尿病,高血压和心血管疾病等肝外疾病也密切相关。
NASH患者起病隐匿,大部分患者早期并没有明显症状,部分患者会出现右上腹隐痛不适、腹胀、恶心呕吐、纳差乏力等,病程进展相对缓慢,容易延误诊断以致疾病的恶化。现阶段NASH的干预手段仍然是以饮食控制和体育锻炼为主,但生活方式和饮食习惯的难以改变、运动缺乏坚持性成为了治疗的严重障碍。目前临床上尚无针对NASH的特效药物,如法尼醇X受体激动剂、PPARα/δ激动剂等靶向药物仍处于临床试验当中,其长期疗效及安全性尚有待评估。再者, NASH的发病机制尚不完全清楚,现有理论认为脂肪毒性、肠道、炎症等多重因素的共同作用下发生。由此看来,NASH的治疗需要针对多种靶点与机制且安全的药物组合。中医药在治疗NASH具有安全性、针对性等的明显优势,中药复方含有多种有效成分,有多层次、多靶点的治疗特点,在调节机体紊乱方面疗效显著,已成为改善和逆转NAFLD和预防NASH、肝硬化及终末期肝病的重要干预和治疗手段。
中医学没有NAFLD/NASH的明确病名,但根据其临床表现,大多归属于中医“肝癖”“胁痛”“积聚”等病证范畴。早在《内经》中就已经有对脂肪肝的相关描述,如《灵枢·邪气藏府病形》中曰“微急为肥气在胁下,若复杯”。《古今医鉴》中论胁痛“若因暴怒伤触悲哀气结,饮食过度···或痰积流注于血,与血相搏,皆能为痛”,指出情志失调、饮食不节是等本病的重要诱因,与痰湿等病理因素密切相关。饮食不节、过食肥甘导致脾虚健运,或情志失调,肝气郁滞,木克脾土,亦能致脾失健运,进而湿浊内停,此阶段病机以肝郁脾虚为主,是单纯性脂肪肝阶段;湿邪日久,郁而化热,而出现湿热内蕴,此阶段便为从单纯性脂肪肝发展成NASH阶段;痰浊不化,阻滞气机,气滞血瘀,瘀血内停,痰瘀互结于肝脏,发展成为肝硬化甚至终末期肝病。可见NASH阶段病机主要是湿热内蕴,治疗应以清热化湿为主。临床上应用清热化湿方剂如茵陈蒿汤、茵陈五苓散等治疗 NASH,均取得良好疗效。
发明内容
本发明为解决现有技术中的上述问题,提出一种具有缓解非酒精性脂肪性肝炎的中药组合物及其制备方法和产品。
为实现上述目的,本发明采用以下技术方案:
本发明的第一个方面是提供一种具有缓解非酒精性脂肪性肝炎的中药组合物,所述中药组合物包含茵陈、白花蛇舌草、栀子根、桑寄生,其由茵陈、白花蛇舌草、栀子根、桑寄生按质量比1:0.8-1.5:0.2-1.2:0.2-1.2配制而成。
进一步地,所述茵陈、白花蛇舌草、栀子根、桑寄生按质量比为1:1:0.5:0.5。
本发明的第二个方面是提供一种中药组合物的制备方法,包括如下步骤:
步骤1,按配方比称取茵陈、白花蛇舌草、栀子根和桑寄生;
步骤2,将茵陈、白花蛇舌草、栀子根、桑寄生按质量比混合后进行水提制得。
进一步地,步骤2中所述水提工艺为:将茵陈、白花蛇舌草、栀子根、桑寄生的混合物在纯水中煮沸40分钟后分离煎出液。
进一步地,所述一种中药组合物的制备方法还包括:
步骤3:将水提后得到的煎出液进行浓缩,即得所述中药组合物。
进一步地,步骤3中所述浓缩工艺为:采用旋转蒸发仪除去煎出液中的溶剂,再用纯水把溶质溶解成3-5g/mL生药浓度的溶液,最后采用微孔膜过滤,即得。
本发明的第三个方面是提供一种中药组合物的食品保健品。
进一步地,所述食品保健品的剂型为胶囊剂、片剂、粉剂、颗粒剂、茶剂或口服液。
本发明的第四个方面是提供一种中药组合物及其药物学上可接受载体的药物制剂。
进一步地,所述载体为微晶纤维素、羟丙基纤维素、硬脂酸镁中的一种或几种。
本发明采用上述技术方案,与现有技术相比,具有如下技术效果:
本发明提供的中药组合物及包含该中药组合物的食品保健品和药物制剂,能够有效减轻肝脏的肿胀,改善肝脏病理变化,减少肝脏脂质蓄积,降低肝脏炎症因子水平,有效缓解NASH的功效;此外,采用该特定配方的四味中药,不仅在中医角度符合NASH的发病机制,同时在现代药理学角度亦与NASH病机有着多方面的契合,拓展了中草药在改善NASH方面的现代意义,安全稳定,适合长期服用。
附图说明
图1和图2为本发明验证试验得到的各组大鼠肝重与肝指数结果对比图;
图3为本发明验证试验过程中各组大鼠肝脏肉眼观察与肝组织HE、油红O 染色结果图;
图4为本发明验证试验得到的各组大鼠肝组织TG水平对比图;
图5和图6为本发明验证试验得到的各组大鼠肝组织TNF-α与IL-1β水平对比图。
具体实施方式
本发明基于传统中医理念,利用现代药理学研究方法验证,发现将茵陈、白花蛇舌草、栀子根、桑寄生的中药组合具有减轻肝脏的肿胀,改善肝脏病理变化,减少肝脏脂质蓄积,降低肝脏炎症因子水平,有效缓解NASH的功效。
具体地,本发明提供一种具有缓解非酒精性脂肪性肝炎的中药组合物,所述中药组合物包含茵陈、白花蛇舌草、栀子根、桑寄生,其由茵陈、白花蛇舌草、栀子根、桑寄生按质量比1:0.8-1.5:0.2-1.2:0.2-1.2配制而成;优选地,茵陈、白花蛇舌草、栀子根、桑寄生按质量比1:1:0.5:0.5配制而成。本发明的中药组合物中,茵陈能清热利湿退黄,是清利肝胆湿热之要药;白花蛇舌草清热利湿,兼能活血;栀子根以助清热利湿;桑寄生能祛风除湿,补益肝肾,以复受损之肝体;诸药合用,共奏清热利湿,活血护肝之功。现代药理学研究表明,茵陈具有利胆,保护肝功能,抗炎,降血脂等作用;白花蛇舌草具有调节免疫、消炎、抗氧化等作用;栀子根具有保肝作用,能用于治疗黄疸型肝炎;桑寄生具有降血压、血糖及血脂,以及抗炎等作用;诸药合用,能发挥降脂、抗炎、保肝等多重作用。
本发明还提供一种中药组合物的制备方法,包括如下步骤:
步骤1,按配方比称取茵陈、白花蛇舌草、栀子根和桑寄生;
步骤2,将茵陈、白花蛇舌草、栀子根、桑寄生按质量比混合后进行水提制得;水提工艺为:将茵陈、白花蛇舌草、栀子根、桑寄生的混合物在纯水中煮沸 40分钟后分离煎出液。
步骤3:将水提后得到的煎出液进行浓缩,即得所述中药组合物。浓缩工艺为:采用旋转蒸发仪除去煎出液中的溶剂,再用纯水把溶质溶解成3-5g/mL生药浓度的溶液,最后采用微孔膜过滤,即得;优选地,用纯水把溶质溶解成4g/mL 生药浓度的溶液,最后采用微孔膜过滤,即得。
本发明还提供一种中药组合物的食品保健品,所述食品保健品的剂型为胶囊剂、片剂、粉剂、颗粒剂、茶剂或口服液。
本发明还提供一种中药组合物及其药物学上可接受载体的药物制剂,所述载体为微晶纤维素、羟丙基纤维素、硬脂酸镁中的一种或几种。
下面通过具体实施例对本发明进行详细和具体的介绍,以使更好的理解本发明,但是下述实施例并不限制本发明范围。
实施例1
一种中药组合物,包括以下重量分数的各组分:
茵陈25份、白花蛇舌草25份、栀子根12.5份、桑寄生12.5份。
一种中药组合物的制备方法:
(1)将所述的茵陈、白花蛇舌草、栀子根、桑寄生混合后在纯水中煮沸40 分钟后分离煎出液;
(2)使用旋转蒸发仪除去煎出液中的溶剂,再用纯水把溶质溶解成3g/mL 生药浓度的溶液,最后用22μm微孔膜过滤得到所述的一种中药组合物。
实施例2
一种中药组合物,包括以下重量分数的各组分:
茵陈25份、白花蛇舌草25份、栀子根12.5份、桑寄生12.5份。
一种中药组合物的制备方法:
(1)将所述的茵陈、白花蛇舌草、栀子根、桑寄生混合后在纯水中煮沸40 分钟后分离煎出液;
(2)使用旋转蒸发仪除去煎出液中的溶剂,再用纯水把溶质溶解成4g/mL 生药浓度的溶液,最后用22μm微孔膜过滤得到所述的一种中药组合物。
实施例3
一种中药组合物,包括以下重量分数的各组分:
茵陈25份、白花蛇舌草25份、栀子根12.5份、桑寄生12.5份。
一种中药组合物的制备方法:
(1)将所述的茵陈、白花蛇舌草、栀子根、桑寄生混合后在纯水中煮沸40 分钟后分离煎出液;
(2)使用旋转蒸发仪除去煎出液中的溶剂,再用纯水把溶质溶解成5g/mL 生药浓度的溶液,最后用22μm微孔膜过滤得到所述的一种中药组合物。
验证试验
1.试验目的:
研究本中药组合物对非酒精性脂肪性肝炎的改善作用。
2.试验材料
2.1试验样品:
复方中药物茵陈、白花蛇舌草、栀子根、桑寄生按1:1:0.5:0.5比例混合,于纯水中煮沸40分钟,使用旋转蒸发仪除去溶剂,再用纯水溶解成3g/mL生药浓度的溶液并用22μm微孔膜过滤。
2.2试验动物
雄性SD大鼠。
3.实验方法
3.1动物造模与给药
7周龄雄性SD大鼠,饲养于SPF级动物房内(温度21±2℃,明暗周期12 小时),自由进行饮食饮水,所有动物实验操作比照NIH颁布实验动物福利及试用指导原则进行。本次实验采用蛋氨酸与胆碱缺乏饲料(Methionine and choline deficient diet,MCD饲料)喂养建立非酒精性脂肪性肝炎大鼠模型,MCD饲料是国际公认的NASH模型建立方法之一,能复制与人类NASH接近的肝脏病理状态。按随机数字表法将大鼠分为4组,即对照组、模型组、高剂量组、低剂量组。其中对照组以MCS饲料(MCD饲料的对照饲料,含蛋氨酸与胆碱)喂养,模型组、高剂量组、低剂量组以MCD饲料喂养;高剂量组、低剂量组在造模同时分别给予3g/kg/d、1g/kg/d剂量的上述复方灌胃,对照组与模型组给予等量的纯水灌胃,持续4周。4周后,测量动物体重后腹腔注射10%水合氯醛(剂量3mL/kg) 麻醉动物,采集肝脏称重,并按照相关方法制备肝组织样品保存待测。
3.2病理学观察
3.2.1肝组织油红O染色
①冰冻切片机箱内温度设定为-25℃、冻头温度设定为-20℃,预冷2h;
②于样品冷冻头上均匀涂上一层OCT包埋剂,箱内冷冻15min;
③取肝右叶相同部位组织置于样品冷冻头上,OCT包埋,箱内冷冻15min;
④切8μm组织薄片,贴片;
⑤油红应用液配制:以体积比5∶2的比例将贮备液与稀释液进行混合,并使用慢速滤纸过滤;
⑥切片室温下静置10min后,于应用液中染15min,37℃温水中洗30s;
⑦苏木素复染3min,流水冲洗1min;
⑧水性封固剂封片,镜检。
3.2.2肝组织HE染色
①取大鼠相同位置肝组织小块,PBS冲洗后置于4%多聚甲醛中固定12h;
②智能自动脱水机脱水;
③常规石蜡包埋;
④石蜡切片机切5μm组织薄片,40℃温水展片,60℃烤片;
⑤常规脱蜡至水;
⑥苏木素复染5min,盐酸酒精分化,PBS冲洗返蓝;
⑦伊红复染3min;
⑧常规脱水至二甲苯;
⑨中性树胶封片,镜检。
3.3肝组织匀浆生化
取100g肝组织,加入0.9mL无水乙醇并制作组织匀浆,4℃、3500rpm离心 10min,取上清,检测肝组织匀浆甘油三酯(TG)浓度。
3.4肝组织炎症因子检测
①设空白孔(空白孔不添加样品、生物素标记的抗体与酶标工作液,其余步骤与其他孔相同)、标准品孔与样品孔,每孔分别加入各浓度标准溶液或样品溶液100μL,覆上板贴,37℃孵育2h;
②弃去液体,甩干,洗涤4次,每次30s,甩干;
③添加生物素标记的抗体每孔100μL,盖上新的板贴,37℃孵育1h;
④弃去液体,甩干,洗涤4次,每次30s,甩干;
⑤添加酶标工作液每孔100μL,盖上新的板贴,37℃孵育30min;
⑥弃去液体,甩干,洗涤4次,每次30s,甩干;
⑦添加底物溶液每孔100μL,37℃避光孵育30min;
⑧添加终止溶液每孔100μL,λ450nm读数;
⑨绘制标准曲线,计算结果。
3.5统计学分析
使用SPSS for Windows 19.0统计数据,数据以平均值±标准偏差(SD)表示,组间差异以one-wayANOVA分析,检验水平P<0.05被认为具有统计学意义。使用GraphPadPrism6.0绘图。
4实验结果
4.1大鼠肝重与肝指数结果
如图1和图2所示,模型组肝脏重量和肝脏指数显着高于对照组(P<0.001),高剂量组和低剂量组大鼠肝脏重量和肝脏指数均低于模型组(P<0.01,P<0.001)。结果表明,本中药组合物可以降低NASH大鼠的肝脏重量和肝脏指数。
4.2大鼠肝脏病理结果
如图3所示,从肝组织形态来看,对照组大鼠肝脏呈暗红色,包膜正常,边缘清晰,触感有弹性。模型组大鼠肝脏肿胀,颜色偏黄,包膜紧张,边缘钝,触感柔软。高剂量组和低剂量组在肝脏大小,颜色和触觉方面优于模型组。HE染色结果显示,对照组大鼠肝组织细胞边界明显,细胞核蓝染位于细胞中心,肝索结构清晰,无明显病变。在模型组的肝脏组织中,存在大量脂肪空泡,甚至相邻的细胞融合成一块,细胞边界不清楚,细胞核被挤到一侧,肝索结构不清楚。与模型组相比,高剂量组和低剂量组大鼠肝组织脂肪空泡减少,肝索结构有一定程度的恢复。油红O染色显示模型组大鼠肝组织中有大量橙红色脂滴,在高剂量组和低剂量组中,脂滴相对减少。结果显示本中药组合物能有效改善NASH大鼠肝组织病理变化,减轻脂肪变性。
4.3大鼠肝组织TG水平
如图4所示,为了分析各组肝组织的TG含量,我们检测了肝匀浆TG水平,模型组肝脏TG水平与对照组相比显著增加(P<0.001),高剂量组和低剂量组肝脏TG水平均较模型组显著降低(P<0.01,P<0.001)。结果表明,本中药组合物能有效降低NASH大鼠肝组织甘油三酯含量。
4.4大鼠肝组织炎症因子水平
如图5和图6所示,与对照组相比,模型组大鼠肝组织TNF-α和IL-1β水平显著升高(P<0.001),高剂量组和低剂量组大鼠肝组织TNF-α和IL-1β水平较模型组明显降低(P<0.05,P<0.01)。结果显示本中药组合物能有效降低NASH大鼠肝组织TNF-α和IL-1β水平。
4.5药效总结
上述实验证明,本中药组合物具有减轻大鼠肝脏的肿胀程度、肝重量,改善肝脏病理变化,减少肝脏脂质蓄积,降低肝脏炎症因子水平,有效缓解NASH 的功效。
以上对本发明的具体实施例进行了详细描述,但其只是作为范例,本发明并不限制于以上描述的具体实施例。对于本领域技术人员而言,任何对本发明进行的等同修改和替代也都在本发明的范畴之中。因此,在不脱离本发明的精神和范围下所作的均等变换和修改,都应涵盖在本发明的范围内。
Claims (7)
1.一种具有缓解非酒精性脂肪性肝炎的中药组合物,其特征在于,所述中药组合物由茵陈、白花蛇舌草、栀子根、桑寄生按质量比1:1:0.5:0.5配制而成。
2.一种如权利要求1所述的中药组合物的制备方法,其特征在于,包括:
步骤1,按配方比称取茵陈、白花蛇舌草、栀子根和桑寄生;
步骤2,将茵陈、白花蛇舌草、栀子根、桑寄生按质量比混合后进行水提;
步骤3,将水提后得到的煎出液进行浓缩,所述浓缩工艺为:采用旋转蒸发仪除去煎出液中的溶剂,再用纯水把溶质溶解成3-5g/mL生药浓度的溶液,最后采用微孔膜过滤,即得所述中药组合物。
3.根据权利要求2所述的中药组合物的制备方法,其特征在于,步骤2中所述水提工艺为:将茵陈、白花蛇舌草、栀子根、桑寄生的混合物在纯水中煮沸40分钟后分离煎出液。
4.一种包含如权利要求1所述中药组合物的食品保健品。
5.根据权利要求4所述的食品保健品,其特征在于,所述食品保健品的剂型为胶囊剂、片剂、粉剂、颗粒剂、茶剂或口服液。
6.一种包含如权利要求1所述中药组合物及药物学上可接受载体的药物制剂。
7.根据权利要求6所述的药物制剂,其特征在于,所述载体为微晶纤维素、羟丙基纤维素、硬脂酸镁中的一种或几种。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910632010.XA CN110339252B (zh) | 2019-07-12 | 2019-07-12 | 一种具有缓解非酒精性脂肪性肝炎的中药组合物及其制备方法和产品 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910632010.XA CN110339252B (zh) | 2019-07-12 | 2019-07-12 | 一种具有缓解非酒精性脂肪性肝炎的中药组合物及其制备方法和产品 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110339252A CN110339252A (zh) | 2019-10-18 |
CN110339252B true CN110339252B (zh) | 2021-09-17 |
Family
ID=68175174
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910632010.XA Active CN110339252B (zh) | 2019-07-12 | 2019-07-12 | 一种具有缓解非酒精性脂肪性肝炎的中药组合物及其制备方法和产品 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110339252B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115887545A (zh) * | 2022-11-25 | 2023-04-04 | 深圳市人民医院 | 一种中药组合物及包含该中药组合物的产品、制备方法及其用途 |
-
2019
- 2019-07-12 CN CN201910632010.XA patent/CN110339252B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN110339252A (zh) | 2019-10-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102600423B (zh) | 用于治疗肝纤维化的中药制备方法 | |
CN103520293B (zh) | 改善和治疗便秘的内服中药 | |
CN102068535B (zh) | 乙醇回流提取的枳实或枳壳总黄酮提取物及其用途 | |
CN102319400B (zh) | 一种用于凉血止血、滋阴化瘀、养肝明目的中药组合物及其制备方法 | |
WO2008061447A1 (fr) | Médicament pour traiter l'eczéma et procédés d'application cutanée de ce médicament | |
CN110339252B (zh) | 一种具有缓解非酒精性脂肪性肝炎的中药组合物及其制备方法和产品 | |
CN101002929A (zh) | 一种治疗功能性消化不良或并发幽门螺旋杆菌感染的药物及其制备方法 | |
CN103120732B (zh) | 一种治疗黄疸的中药组合物及其制备方法 | |
CN107041924A (zh) | 一种防治糖尿病肾病的朝药复方提取物及其制备方法 | |
CN102309705B (zh) | 一种降低血尿酸的药物及其制备方法和用途 | |
CN107753630A (zh) | 一种治疗失眠症的药物组合物及制备方法 | |
CN101919985A (zh) | 一种治疗脂肪肝的药物及其制备方法和用途 | |
CN101455778B (zh) | 一种清热利咽的中药制剂及其制备方法 | |
CN104161850A (zh) | 一种中药提取物的制备方法及其制备的中药提取物和用途 | |
CN104042928B (zh) | 一种治疗糖尿病的药物组合物及其制备方法和用途 | |
CN103585495B (zh) | 一种治疗糖尿病肾损害的胶囊 | |
CN103750304B (zh) | 一种泽泻减肥降脂保健口服液及其制备方法 | |
CN106619977A (zh) | 防治类风湿性关节炎的药物组合物 | |
CN106109767A (zh) | 一种防治非酒精性脂肪性肝病的复方制剂 | |
CN103041288B (zh) | 一种治疗糖尿病性脂肪肝的中药组成及制备工艺 | |
CN101884700A (zh) | 一种含茶的中药组合物 | |
CN101874830B (zh) | 萸炙黄连炮制品的新用途 | |
CN103655970A (zh) | 山楂泻籽软胶囊及其制备方法 | |
CN108210595A (zh) | 治疗慢加急性肝衰竭的中药组合物及其制备方法和应用 | |
CN103494851B (zh) | 一种胃舒欣制剂的制备方法 |
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 | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20201015 Address after: 518000 No. 1017 Dongmen North Road, Guangdong, Shenzhen Applicant after: SHENZHEN PEOPLE'S Hospital Address before: 518000 No. 1017 Dongmen North Road, Guangdong, Shenzhen Applicant before: SHENZHEN PEOPLE'S Hospital Applicant before: Shenzhen Huiyun Pharmaceutical Technology Co.,Ltd. |
|
TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant |