CN118078942A - Composition and granule preparation for treating obstructive sleep apnea-hypopnea syndrome and preparation method thereof - Google Patents
Composition and granule preparation for treating obstructive sleep apnea-hypopnea syndrome and preparation method thereof Download PDFInfo
- Publication number
- CN118078942A CN118078942A CN202410223559.4A CN202410223559A CN118078942A CN 118078942 A CN118078942 A CN 118078942A CN 202410223559 A CN202410223559 A CN 202410223559A CN 118078942 A CN118078942 A CN 118078942A
- Authority
- CN
- China
- Prior art keywords
- mixture
- mixing
- composition
- preparation
- extract
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 165
- 238000002360 preparation method Methods 0.000 title claims abstract description 62
- 208000001797 obstructive sleep apnea Diseases 0.000 title claims abstract description 43
- 201000002859 sleep apnea Diseases 0.000 title claims abstract description 34
- 239000008187 granular material Substances 0.000 title claims description 9
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims abstract description 21
- 235000003140 Panax quinquefolius Nutrition 0.000 claims abstract description 21
- 235000008434 ginseng Nutrition 0.000 claims abstract description 21
- 241000132012 Atractylodes Species 0.000 claims abstract description 19
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims abstract description 19
- 235000017443 Hedysarum boreale Nutrition 0.000 claims abstract description 19
- 235000007858 Hedysarum occidentale Nutrition 0.000 claims abstract description 19
- 239000001947 glycyrrhiza glabra rhizome/root Substances 0.000 claims abstract description 19
- 241000255789 Bombyx mori Species 0.000 claims abstract description 18
- 240000005528 Arctium lappa Species 0.000 claims abstract description 17
- 235000003130 Arctium lappa Nutrition 0.000 claims abstract description 17
- 235000008078 Arctium minus Nutrition 0.000 claims abstract description 17
- 241000931705 Cicada Species 0.000 claims abstract description 17
- 235000006533 astragalus Nutrition 0.000 claims abstract description 16
- 244000246386 Mentha pulegium Species 0.000 claims abstract description 15
- 235000016257 Mentha pulegium Nutrition 0.000 claims abstract description 15
- 235000004357 Mentha x piperita Nutrition 0.000 claims abstract description 15
- 235000001050 hortel pimenta Nutrition 0.000 claims abstract description 15
- 241000906579 Actaea cimicifuga Species 0.000 claims abstract description 14
- 241000112528 Ligusticum striatum Species 0.000 claims abstract description 13
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 claims abstract description 13
- 244000197580 Poria cocos Species 0.000 claims abstract description 12
- 235000008599 Poria cocos Nutrition 0.000 claims abstract description 12
- 244000303040 Glycyrrhiza glabra Species 0.000 claims abstract 3
- 244000131316 Panax pseudoginseng Species 0.000 claims abstract 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 161
- 238000002156 mixing Methods 0.000 claims description 76
- 239000000284 extract Substances 0.000 claims description 62
- 235000019441 ethanol Nutrition 0.000 claims description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 47
- 238000010992 reflux Methods 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 36
- 239000000706 filtrate Substances 0.000 claims description 25
- 238000001914 filtration Methods 0.000 claims description 25
- 108090000790 Enzymes Proteins 0.000 claims description 23
- 102000004190 Enzymes Human genes 0.000 claims description 23
- 229940088598 enzyme Drugs 0.000 claims description 23
- 239000000463 material Substances 0.000 claims description 22
- 238000000605 extraction Methods 0.000 claims description 18
- 238000009835 boiling Methods 0.000 claims description 17
- 238000002791 soaking Methods 0.000 claims description 17
- 238000009472 formulation Methods 0.000 claims description 15
- 241001522129 Pinellia Species 0.000 claims description 13
- 239000012535 impurity Substances 0.000 claims description 12
- 241001061264 Astragalus Species 0.000 claims description 11
- 210000004233 talus Anatomy 0.000 claims description 11
- 108010059892 Cellulase Proteins 0.000 claims description 10
- 229940106157 cellulase Drugs 0.000 claims description 10
- 238000007908 dry granulation Methods 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 8
- 241001619461 Poria <basidiomycete fungus> Species 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 238000010298 pulverizing process Methods 0.000 claims description 6
- 241000202726 Bupleurum Species 0.000 claims description 5
- 244000170916 Paeonia officinalis Species 0.000 claims description 5
- 235000006484 Paeonia officinalis Nutrition 0.000 claims description 5
- 229940107666 astragalus root Drugs 0.000 claims description 5
- 240000007164 Salvia officinalis Species 0.000 claims description 4
- 240000004534 Scutellaria baicalensis Species 0.000 claims description 4
- 235000017089 Scutellaria baicalensis Nutrition 0.000 claims description 4
- 241000206501 Actaea <angiosperm> Species 0.000 claims description 3
- 244000180303 Agastache foeniculum Species 0.000 claims description 3
- 235000010685 Agastache foeniculum Nutrition 0.000 claims description 3
- 241000212322 Levisticum officinale Species 0.000 claims description 3
- 239000001645 levisticum officinale Substances 0.000 claims description 3
- 235000005412 red sage Nutrition 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 30
- 239000002994 raw material Substances 0.000 abstract description 23
- 239000003814 drug Substances 0.000 abstract description 19
- 241000045403 Astragalus propinquus Species 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 41
- 241000699670 Mus sp. Species 0.000 description 23
- 210000004369 blood Anatomy 0.000 description 22
- 239000008280 blood Substances 0.000 description 22
- 230000000052 comparative effect Effects 0.000 description 20
- 206010062717 Increased upper airway secretion Diseases 0.000 description 18
- 240000004371 Panax ginseng Species 0.000 description 18
- 208000026435 phlegm Diseases 0.000 description 18
- 208000024891 symptom Diseases 0.000 description 18
- 210000000952 spleen Anatomy 0.000 description 17
- 241000244355 Ligusticum Species 0.000 description 16
- 206010041235 Snoring Diseases 0.000 description 12
- 210000004072 lung Anatomy 0.000 description 12
- 238000000465 moulding Methods 0.000 description 10
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 9
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 230000001737 promoting effect Effects 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 9
- 102100037850 Interferon gamma Human genes 0.000 description 8
- 108010074328 Interferon-gamma Proteins 0.000 description 8
- 108090000978 Interleukin-4 Proteins 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 238000003745 diagnosis Methods 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 210000002850 nasal mucosa Anatomy 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000004375 Dextrin Substances 0.000 description 6
- 229920001353 Dextrin Polymers 0.000 description 6
- 206010041349 Somnolence Diseases 0.000 description 6
- 235000019425 dextrin Nutrition 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 210000000492 nasalseptum Anatomy 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 210000002784 stomach Anatomy 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 206010021143 Hypoxia Diseases 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 208000032023 Signs and Symptoms Diseases 0.000 description 4
- 208000031975 Yang Deficiency Diseases 0.000 description 4
- 230000004087 circulation Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 235000008216 herbs Nutrition 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 230000007958 sleep Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 3
- 208000032140 Sleepiness Diseases 0.000 description 3
- 208000008784 apnea Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 210000005069 ears Anatomy 0.000 description 3
- 206010016256 fatigue Diseases 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 230000007954 hypoxia Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000001331 nose Anatomy 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 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 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 206010021079 Hypopnoea Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010068319 Oropharyngeal pain Diseases 0.000 description 2
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 2
- 201000007100 Pharyngitis Diseases 0.000 description 2
- 241000863480 Vinca Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000012869 ethanol precipitation Methods 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 244000144993 groups of animals Species 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 230000027939 micturition Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000037321 sleepiness Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000049624 Alisma plantago-aquatica subsp. orientale Species 0.000 description 1
- 241001254604 Angelica pubescens Species 0.000 description 1
- XOJVHLIYNSOZOO-SWOBOCGESA-N Arctiin Chemical compound C1=C(OC)C(OC)=CC=C1C[C@@H]1[C@@H](CC=2C=C(OC)C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)=CC=2)C(=O)OC1 XOJVHLIYNSOZOO-SWOBOCGESA-N 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 241000037740 Coptis chinensis Species 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
- 241000721047 Danaus plexippus Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 239000009636 Huang Qi Substances 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021133 Hypoventilation Diseases 0.000 description 1
- 241000244365 Ligusticum sinense Species 0.000 description 1
- 206010024642 Listless Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 244000236658 Paeonia lactiflora Species 0.000 description 1
- 235000008598 Paeonia lactiflora Nutrition 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 206010039203 Road traffic accident Diseases 0.000 description 1
- 235000017276 Salvia Nutrition 0.000 description 1
- 241001180876 Saposhnikovia Species 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 206010042434 Sudden death Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940104299 cimicifugae rhizoma Drugs 0.000 description 1
- 229940124301 concurrent medication Drugs 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 235000020709 ginseng supplement Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000010832 independent-sample T-test Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 208000017971 listlessness Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004373 mandible Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000004206 stomach function Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000009966 trimming Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides a composition for treating obstructive sleep apnea-hypopnea syndrome, a granular preparation and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine preparations. The composition provided by the invention is prepared from 5-10 g of astragalus membranaceus, 1-3 g of bighead atractylodes rhizome, 1-2 g of dried orange peel, 3-8 g of cimicifuga foetida, 3-6 g of radix bupleuri, 3-5 g of radix scutellariae, 2-4 g of sun-dried ginseng, 2-4 g of honey-fried licorice root, 1-4 g of peppermint, 2-6 g of burdock, 2-8 g of stiff silkworm, 2-4 g of periostracum cicada, 1-4 g of ligusticum wallichii, 4-8 g of radix curcumae, 5-10 g of rhizoma acori graminei, 2-6 g of radix salviae miltiorrhizae, 2-5 g of rhizoma pinelliae preparata, 1-4 g of poria cocos and 1-4 g of radix paeoniae alba. The invention greatly reduces the dosage of each raw material of the composition, and achieves the effects of remarkably treating obstructive sleep apnea hypopnea syndrome with good curative effect and quick effect on the basis of remarkably reducing cost by adjusting the proportion relation of the raw material and improving the preparation process.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a composition for treating obstructive sleep apnea hypopnea syndrome, a granular preparation and a preparation method thereof.
Background
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep respiratory disease of unknown etiology characterized by intermittent sleep apnea and/or reduced ventilation, and is characterized by nocturnal sleep snoring, daytime sleepiness, fatigue, weakness, etc. The repeated intermittent hypoxia caused by the intermittent apnea and/or hypopnea in the sleeping process is similar to ischemia/reperfusion injury mechanism, and can cause systemic oxidative stress, inflammatory reaction and enhancement of sympathetic nerve activity, and various complications are caused, and the multiple systems such as cardiovascular and cerebrovascular systems, nerves, endocrine systems, genitourinary systems, digestion systems, blood systems and the like are involved. The repeated night hypoxia and hypercarbonated blood diseases caused by the apnea can lead to complications such as hypertension, coronary heart disease, diabetes, cerebrovascular diseases and traffic accidents, and even night sudden death. OSAHS is therefore a potentially fatal sleep respiratory disorder.
Because of the complex etiology and lesion sites of OSAHS, there is no method available to treat all OSAHS patients. At present, the medicines for treating snoring by Western medicine have a plurality of medicines, namely, acetazolamide and thyroxine tablet promote metabolism, have a certain effect, and can be relieved but can not be cured during taking. Although related reports on treating OSAHS of traditional Chinese medicine preparations exist at present, most of the problems of poor curative effect, long time for acting, high cost and the like exist. Therefore, the field needs to provide a traditional Chinese medicine preparation with good curative effect, quick response and low cost.
Disclosure of Invention
In view of the above, the invention aims to provide a traditional Chinese medicine composition with good curative effect, quick response and low cost and a preparation method thereof.
The invention also aims to provide a traditional Chinese medicine granule preparation with good curative effect, quick response and low cost and a preparation method thereof.
In order to achieve the above object, the present invention provides the following technical solutions:
The invention provides a composition for treating obstructive sleep apnea-hypopnea syndrome, which is prepared from the following raw materials: 5-10 g of astragalus root, 1-3 g of bighead atractylodes rhizome, 1-2 g of dried orange peel, 3-8 g of cimicifuga rhizome, 3-6 g of bupleurum root, 3-5 g of baikal skullcap root, 2-4 g of sun-dried ginseng, 2-4 g of honey-fried licorice root, 1-4 g of peppermint, 2-6 g of burdock, 2-8 g of stiff silkworm, 2-4 g of cicada slough, 1-4 g of szechuan lovage rhizome, 4-8 g of radix curcumae, 5-10 g of grassleaf sweelflag rhizome, 2-6 g of red sage root, 2-5 g of purified pinellia tuber, 1-4 g of poria cocos and 1-4 g of white paeony root.
The invention also provides a preparation method of the composition, which comprises the following steps: mixing astragalus, bighead atractylodes rhizome, dried orange peel and cimicifuga foetida to obtain a mixture 1, mixing the mixture 1 with 40-50% ethanol solution by volume fraction, and carrying out reflux extraction to obtain a reflux extract 1; mixing radix bupleuri, radix scutellariae, sun-dried ginseng, honey-fried licorice root and mint to obtain a mixture 2, mixing and soaking the mixture 2 with water, then decocting, keeping boiling for 15-25 min, filtering and taking filtrate as decoction; mixing burdock, stiff silkworm, cicada slough, ligusticum wallichii and radix curcumae to obtain a mixture 3, mixing and soaking the mixture 3 with water, then decocting, keeping boiling for 30-40 min, filtering, taking filtrate, adding absolute ethyl alcohol until the concentration of an ethanol solution is 50-60%, filtering to remove impurities, taking filtrate to recover ethanol to obtain an extract 1, mixing the extract 1 with absolute ethyl alcohol until the concentration of the ethanol solution is 80-90%, filtering to remove impurities, and taking filtrate to recover ethanol to obtain an extract 2; mixing rhizoma Acori Graminei, saviae Miltiorrhizae radix, purified pinellia Tuber, poria and radix Paeoniae alba to obtain mixture 4, mixing the mixture 4 with water and complex enzyme for enzymolysis, heating and reflux extracting the enzymolysis solution to obtain reflux extract 2; the complex enzyme consists of cellulase and pectase; mixing the reflux extract 1, decoction, extract 2 and reflux extract 2, concentrating to obtain extract, drying, and pulverizing to obtain the composition.
Preferably, the weight-volume ratio of the mixture 1 to the ethanol solution with the volume fraction of 40-50% is 1g: 8-12 mL.
Preferably, the soaking time is 20-30 min.
Preferably, the weight to volume ratio of the mixture 2 to water is 1g: 5-8 mL, wherein the weight-volume ratio of the mixture 3 to water is 1g: 7-10 mL.
Preferably, the temperature of the enzymolysis is 35-45 ℃, the time of the enzymolysis is 30-50 min, and the pH value of the enzymolysis is 3.5-6.5.
Preferably, the amount of the complex enzyme is 0.06g-0.09g of the complex enzyme added to 1g of the mixture 4, and the weight ratio of the cellulase to the pectase is 1:2-3.
The invention also provides a granular preparation for treating obstructive sleep apnea-hypopnea syndrome, which consists of the composition and auxiliary materials.
Preferably, the weight ratio of the composition to the auxiliary materials is 1:1.5 to 3.
The invention also provides a preparation method of the granular preparation, which comprises the following steps: and mixing the composition with auxiliary materials, and performing dry granulation to obtain the granular preparation.
The invention has the beneficial effects that:
The invention greatly reduces the dosage of each raw material medicine in the composition on the basis of ensuring the treatment of the obstructive sleep apnea-hypopnea syndrome, and finally achieves the effect of remarkably treating the obstructive sleep apnea-hypopnea syndrome with good curative effect and quick effect on the basis of remarkably reducing the cost by adjusting the proportion relation of each raw material medicine and improving the preparation process. The invention has the advantages of treating both symptoms and root causes, tonifying lung qi, lifting spleen yang qi, clearing lung heat, promoting blood circulation, cooling blood, dispelling melancholy to dredge throat orifices, thereby facilitating the flow of zong qi to promote qi and blood and breathe.
The composition and the granular preparation can achieve the effects of promoting qi circulation, cooling blood, removing blood stasis, eliminating phlegm, inducing resuscitation, promoting blood circulation, eliminating dampness, resolving phlegm, resolving masses, detoxifying, relieving sore throat and inducing resuscitation. Meanwhile, the composition and the granular preparation can achieve the effect of treating OSAHS by reducing the concentration level of HIF-1 alpha, IFN-gamma and IL-4. The composition and the granular preparation have the effect of resisting inflammation by inhibiting the expression of NF- κB in nasal mucosa. The cure rate of the composition and the granular preparation for the obstructive sleep apnea-hypopnea syndrome can reach more than 90%, and the composition and the granular preparation are safe and have no side effect.
Drawings
FIG. 1 shows comparison of HIF-1. Alpha., IFN-gamma., IL-4 levels in serum of mice in each group;
FIG. 2 shows NF- κB positive area fraction results for each group of mice;
FIG. 3 shows the results of the expression changes of NF- κ BmRNA in mouse nasal mucosa tissue;
FIG. 4 shows the change in food intake (g/d) in rats;
FIG. 5 shows the body weight change (g) of rats.
Detailed Description
The invention provides a composition for treating obstructive sleep apnea-hypopnea syndrome, which is prepared from the following raw materials: 5-10 g of astragalus root, 1-3 g of bighead atractylodes rhizome, 1-2 g of dried orange peel, 3-8 g of cimicifuga rhizome, 3-6 g of bupleurum root, 3-5 g of baikal skullcap root, 2-4 g of sun-dried ginseng, 2-4 g of honey-fried licorice root, 1-4 g of peppermint, 2-6 g of burdock, 2-8 g of stiff silkworm, 2-4 g of cicada slough, 1-4 g of szechuan lovage rhizome, 4-8 g of radix curcumae, 5-10 g of grassleaf sweelflag rhizome, 2-6 g of red sage root, 2-5 g of purified pinellia tuber, 1-4 g of poria cocos and 1-4 g of white paeony root.
The invention provides a composition for treating obstructive sleep apnea hypoventilation syndrome (snore) based on the guidance of 'zong qi', and the theoretical basis of treating snore by applying 'zong qi' is as follows: the composition of the religious gas comprises two parts: firstly, the lung inhales clear qi, and secondly, the spleen and stomach absorbs food essence. Function of religious qi: let the respiratory tract and run through the heart vessels to promote qi and blood, and "Ling Shu-Ji-Gu" cloud: the pectoral qi accumulates in the chest and is passed through the throat to breathe with the heart pulse. If the lung is qi-deficiency, the lung inhales the clear qi and has weakened function; if spleen qi deficiency, impaired spleen and stomach function and abnormal transportation and transformation are caused, phlegm dampness is easy to generate, qi deficiency and phlegm obstruction are caused for a long time to form blood stasis, phlegm qi and blood stasis stagnate in the throat, spleen is also a main muscle, and throat muscle is weak and relaxed, and snoring is aggravated. Therefore, the Chinese medicinal composition has the effects of tonifying lung qi, lifting spleen yang qi, promoting blood circulation, cooling blood, dispelling stagnation, dredging throat orifices, promoting the circulation of qi and blood, and relieving respiration, and can be used for leading phlegm and blood stasis and qi stagnation of snoring patients to cross the throat from the source, dredging and eliminating the phlegm and blood stasis and qi stagnation, and improving the snoring symptoms. According to the pathogenesis of the disease, the disease is distinguished by syndrome differentiation, and the formula of the invention is formed, but the formula is not seemingly obvious only in tonifying middle-jiao and Qi.
The composition of the invention is characterized by the following symptoms: spleen yang deficiency, damp turbidity and phlegm stasis in the interior. Pathogenesis analysis: due to fatigue, spleen yang deficiency, weakness of spleen and stomach, long-term damp-heat retention, qi movement obstruction, excessive qi and fire, the body fluid is burned to produce phlegm, phlegm stasis blocks collaterals to cause qi movement discontrol, throat obstruction is unfavorable, and snoring occurs. Weakness of spleen and stomach, phlegm stagnation and obstruction of collaterals can cause lassitude, stuffiness and lying down, chest and diaphragm stuffiness, limb heaviness, or dizziness, palpitation, headache, tasteless and indigestion; after a long time, heat accumulated in the throat is unfavorable or red and swollen, bitter taste and dry tongue; cough and expectoration are caused by phlegm heat accumulated in the lung; damp-heat causes irregular stool and frequent urination; a white or greasy tongue coating and a slippery, astringent or thin pulse are all symptoms of spleen-yang deficiency and phlegm stasis obstructing collaterals.
The composition of the invention is formulated as follows: astragalus root, radix astragali, with the effects of strengthening the spleen and tonifying middle-jiao, lifting yang and trapping yang, expelling toxin and promoting granulation, and tonifying qi and nourishing blood, is mainly indicated for qi deficiency of the lung and spleen. The sun-dried ginseng supplements the five zang organs and calms the spirit. Atractylodis rhizoma has effects of invigorating spleen and qi, dispelling pathogenic wind, cold and dampness arthralgia, removing dead muscle, eliminating phlegm and water, and invigorating body fluid. Astragalus root, sun-dried ginseng (ginseng) and white atractylodes rhizome are all monarch drugs for invigorating spleen qi and tonifying lung qi so as to facilitate the generation and operation of zong qi. Cimicifugae rhizoma, bupleuri radix, pericarpium Citri Tangerinae, rhizoma Pinelliae and Poria, with effects of invigorating yang, invigorating spleen, regulating qi-flowing, removing dampness, scutellariae radix, radix Paeoniae alba, clearing lung heat, astringing yin and nourishing yin, and promoting the circulation of qi. With the assistance of radix curcumae, rhizoma ligustici wallichii and radix salviae miltiorrhizae, promoting qi circulation, cooling blood, removing blood stasis, removing phlegm, inducing resuscitation, promoting blood circulation, eliminating dampness, resolving stiff silkworm, cicada slough, fructus arctii and peppermint, resolving phlegm, resolving masses, detoxifying, relieving sore throat and inducing resuscitation; licorice root, radix Glycyrrhizae Praeparata regulates the drugs. In conclusion, the Chinese medicinal composition treats both symptoms and root causes, supplements lung qi, lifts qi of spleen yang, simultaneously clears lung heat, promotes blood circulation, cools blood, relieves depression to clear throat orifices, thereby facilitating the flow of qi and blood, and prevents respiration, so that snore patients cross phlegm and blood stasis on the throat from the source to dredge and clear, and the snore symptom is improved, so that the effect of effective treatment is achieved. Meanwhile, the selected medicinal materials in the formula are non-toxic Chinese medicinal decoction pieces, and the prepared composition does not produce acute toxicity.
In the present invention, the composition is preferably made from the following raw materials: 6-8 g of astragalus, 2g of bighead atractylodes rhizome, 2g of dried orange peel, 4-6 g of cimicifuga foetida, 4-5 g of radix bupleuri, 4g of radix scutellariae, 3g of sun-dried ginseng, 3g of honey-fried licorice root, 3g of peppermint, 3-5 g of burdock, 3-6 g of stiff silkworm, 3g of cicada slough, 2-3 g of ligusticum wallichii, 5-6 g of radix curcumae, 6-8 g of rhizoma acori graminei, 3-5 g of radix salviae miltiorrhizae, 3-4 g of purified pinellia tuber, 2-3 g of poria cocos and 2-3 g of white paeony root; more preferably, the material is prepared from the following raw materials: 7g of astragalus, 2g of bighead atractylodes rhizome, 2g of dried orange peel, 5g of cimicifuga foetida, 4g of radix bupleuri, 4g of radix scutellariae, 3g of sun-dried ginseng, 3g of honey-fried licorice root, 3g of peppermint, 4g of burdock, 4-5 g of stiff silkworm, 3g of cicada slough, 2g of ligusticum wallichii, 5g of radix curcumae, 7g of rhizoma acori graminei, 4g of radix salviae miltiorrhizae, 3g of rhizoma pinelliae, 2g of poria cocos and 2g of radix paeoniae alba. The specific sources of the above raw materials are not particularly limited, and the present invention may employ products conventionally commercially available in the art.
The invention also provides a preparation method of the composition, which comprises the following steps: mixing astragalus, bighead atractylodes rhizome, dried orange peel and cimicifuga foetida to obtain a mixture 1, mixing the mixture 1 with 40-50% ethanol solution by volume fraction, and carrying out reflux extraction to obtain a reflux extract 1; mixing radix bupleuri, radix scutellariae, sun-dried ginseng, honey-fried licorice root and mint to obtain a mixture 2, mixing and soaking the mixture 2 with water, then decocting, keeping boiling for 15-25 min, filtering and taking filtrate as decoction; mixing burdock, stiff silkworm, cicada slough, ligusticum wallichii and radix curcumae to obtain a mixture 3, mixing and soaking the mixture 3 with water, then decocting, keeping boiling for 30-40 min, filtering, taking filtrate, adding absolute ethyl alcohol until the concentration of an ethanol solution is 50-60%, filtering to remove impurities, taking filtrate to recover ethanol to obtain an extract 1, mixing the extract 1 with absolute ethyl alcohol until the concentration of the ethanol solution is 80-90%, filtering to remove impurities, and taking filtrate to recover ethanol to obtain an extract 2; mixing rhizoma Acori Graminei, saviae Miltiorrhizae radix, purified pinellia Tuber, poria and radix Paeoniae alba to obtain mixture 4, mixing the mixture 4 with water and complex enzyme for enzymolysis, heating and reflux extracting the enzymolysis solution to obtain reflux extract 2; the complex enzyme consists of cellulase and pectase; mixing the reflux extract 1, decoction, extract 2 and reflux extract 2, concentrating to obtain extract, drying, and pulverizing to obtain the composition.
In the preparation method of the invention, the extraction of the effective components is preferably carried out after all the medicinal herbs in the composition are crushed. The method of the present invention is not particularly limited, and grinding is preferable, and sieving with a 50-100 mesh sieve after grinding is completed. In the preparation method of the invention, the weight-to-volume ratio of the mixture 1 to the ethanol solution with the volume fraction of 40-50% is preferably 1g:8 to 12mL, more preferably 1g: 9-11 mL, most preferably 1g:10mL. In the present invention, the concentration (volume fraction) of the ethanol solution obtained in the reflux extraction liquid 1 is preferably 45%, the number of times of the reflux extraction is preferably 2 to 3, the time of each reflux extraction is preferably 0.5 to 1h, and the addition amount of the ethanol solution in the second or third reflux extraction is half the addition amount of the ethanol solution in the previous reflux extraction.
In the present invention, the weight to volume ratio of the mixture 2 to water is preferably 1g:5 to 8mL, more preferably 1g: 6-7 mL, mixing the mixture 2 with water, and soaking for preferably 20-30 min, more preferably 25-28 min, and decocting for preferably 18-22 min, more preferably 19-20 min.
In the present invention, the weight to volume ratio of the mixture 3 to water is preferably 1g:7 to 10mL, more preferably 1g: 8-9 mL, mixing the mixture 3 with water, and soaking for preferably 20-30 min, more preferably 25-28 min, and decocting for preferably 33-37 min, more preferably 35-36 min. The method is not particularly limited to a specific mode of recovering ethanol, and a conventional method for recovering ethanol after water extraction and ethanol precipitation in the field can be adopted. After the extract 1 is obtained, the extract 1 is mixed with absolute ethanol until the concentration of the ethanol solution is preferably 85%, and the ethanol is recovered after the ethanol precipitation part is removed, as described above, and the description thereof will be omitted.
In the invention, the weight ratio of the cellulase to the pectase in the complex enzyme is preferably 1:2-3, the dosage of the complex enzyme is preferably 0.07g-0.08g of the complex enzyme is added to 1g of the mixture 4, and the weight volume ratio of the mixture 4 to water is preferably 1g:8 ml-10 ml, the enzymolysis temperature is preferably 35-45 ℃, more preferably 38-40 ℃, the enzymolysis time is preferably 30-50 min, more preferably 35-45 min, and the pH value of the enzymolysis is preferably 3.5-6.5, more preferably 4.5-5.5. In the invention, when the enzymatic hydrolysate is subjected to reflux extraction, the times of the reflux extraction are preferably 2 times, and the time of each reflux extraction is preferably 20-30 min.
In the preparation method of the invention, the methods for respectively obtaining the reflux extract 1, the decoction, the extract 2 and the reflux extract 2 are not sequential, the four substances are obtained and then mixed and concentrated, the specific method of the invention is not particularly limited, the method for concentrating is a method for concentrating into extractum conventionally in the field, the drying temperature is preferably 40-50 ℃, and the water content is dried to be lower than 10%, so that the composition is obtained.
According to the preparation method, 40% -50% of alcohol-soluble components of astragalus membranaceus, bighead atractylodes rhizome, dried orange peel and cimicifuga foetida are obtained pertinently, water-soluble and non-volatile components of radix bupleuri, radix scutellariae, sun-dried ginseng, honey-fried licorice root and peppermint are obtained, water-soluble and non-volatile components of burdock, stiff silkworm, periostracum cicadae, ligusticum chuanxiong and radix curcumae are dissolved in water but not in 50% -60% and 80% -90% of alcohol-soluble components, and enzymolysis water-soluble and non-volatile components of rhizoma acori graminei, radix salviae miltiorrhizae, purified pinellia ternate, poria cocos and radix paeoniae alba can be removed, the dissolution rate of beneficial components is greatly improved, and interaction occurs among the active components of each medicine in the process of mixing and extracting the components, so that the remarkable treatment effect can be achieved on the basis of greatly reducing the dosage of raw materials.
The invention also provides a granular preparation for treating obstructive sleep apnea-hypopnea syndrome, which consists of the composition and auxiliary materials. In the granular preparation of the invention, the composition is used in an amount of one medicament, and one medicament can be used in one day.
In the invention, the weight ratio of the composition to the auxiliary materials is preferably 1:1.5 to 3, more preferably 1:2.5. in the present invention, the auxiliary material preferably includes at least one of sucralose and dextrin.
The invention also provides a preparation method of the granular preparation, which comprises the following steps: and mixing the composition with auxiliary materials, and performing dry granulation to obtain the granular preparation. The specific method of dry granulation is not particularly limited in the present invention, and conventional dry granulation methods in the art may be employed.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
In the following examples, conventional methods are used unless otherwise specified.
Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
Example 1
A composition for treating obstructive sleep apnea hypopnea syndrome, the composition being made from: 7g of astragalus, 2g of bighead atractylodes rhizome, 2g of dried orange peel, 5g of cimicifuga foetida, 5g of radix bupleuri, 4g of radix scutellariae, 3g of sun-dried ginseng, 3g of honey-fried licorice root, 3g of peppermint, 4g of burdock, 5g of stiff silkworm, 3g of cicada slough, 2g of ligusticum wallichii, 5g of radix curcumae, 7g of rhizoma acori graminei, 4g of radix salviae miltiorrhizae, 3g of rhizoma pinelliae preparata, 2g of poria cocos and 2g of radix paeoniae alba.
Example 2
A composition for treating obstructive sleep apnea hypopnea syndrome, the composition being made from: 5g of astragalus, 1g of bighead atractylodes rhizome, 1g of dried orange peel, 3g of cimicifuga foetida, 3g of radix bupleuri, 3g of radix scutellariae, 2g of sun-dried ginseng, 2g of honey-fried licorice root, 1g of peppermint, 2g of burdock, 2g of stiff silkworm, 2g of cicada slough, 1g of ligusticum wallichii, 4g of radix curcumae, 5g of rhizoma acori graminei, 2g of radix salviae miltiorrhizae, 2g of rhizoma pinelliae preparata, 1g of poria cocos and 1g of radix paeoniae alba.
Example 3
A composition for treating obstructive sleep apnea hypopnea syndrome, the composition being made from: 10g of astragalus, 3g of bighead atractylodes rhizome, 2g of dried orange peel, 8g of cimicifuga foetida, 6g of bupleurum, 5g of scutellaria baicalensis, 4g of sun-dried ginseng, 4g of honey-fried licorice root, 4g of peppermint, 6g of burdock, 8g of stiff silkworm, 4g of cicada slough, 4g of ligusticum wallichii, 8g of radix curcumae, 10g of grassleaf sweelflag rhizome, 6g of red-rooted salvia root, 5g of purified pinellia tuber, 4g of poria cocos and 4g of white paeony root.
Example 4
The composition for treating obstructive sleep apnea-hypopnea syndrome described in example 1 was prepared by the following steps: the raw material herbs described in example 1 were pulverized by a polisher and sieved with a 50-mesh sieve to obtain raw material powders. The raw material powders were accurately weighed according to the amounts of the raw material flavors described in example 1, and the following procedure was performed:
mixing astragalus, bighead atractylodes rhizome, dried orange peel and cimicifuga foetida to obtain a mixture 1, and mixing the mixture 1 with 45% ethanol solution according to the weight-to-volume ratio of 1g: mixing 9mL, reflux-extracting for 0.6h for 1 st time, adding 45% ethanol solution (according to the weight-volume ratio of the mixture 1 and the 45% ethanol solution of 1g:4.5 mL), reflux-extracting for 2 nd time for 0.5h to obtain reflux extract 1;
mixing radix bupleuri, radix scutellariae, sun-dried ginseng, honey-fried licorice root and peppermint to obtain a mixture 2, and mixing the mixture 2 with water according to the weight-to-volume ratio of 1g: mixing at a ratio of 6mL, soaking for 25min, decocting, boiling, keeping boiling state for 19min, filtering, and collecting filtrate as decoction;
Mixing burdock, stiff silkworm, periostracum cicada, ligusticum wallichii and radix curcumae to obtain a mixture 3, and mixing the mixture 3 with water according to the weight-volume ratio of 1g: mixing 9mL, soaking for 25min, decocting, boiling, keeping boiling for 35min, filtering, collecting filtrate, adding absolute ethanol until the concentration of ethanol solution is 55%, filtering, removing impurities, collecting filtrate, recovering ethanol to obtain extract 1, mixing extract 1 with absolute ethanol until the concentration of ethanol solution is 85%, filtering, removing impurities, collecting filtrate, and recovering ethanol to obtain extract 2;
Mixing rhizoma Acori Graminei, saviae Miltiorrhizae radix, purified pinellia Tuber, poria and radix Paeoniae alba to obtain mixture 4, mixing the mixture 4 with water and compound enzyme for enzymolysis (the weight ratio of cellulase and pectase in the compound enzyme is 1:3, the compound enzyme is 1g:9ml:0.07g, the enzymolysis temperature is 38deg.C, the enzymolysis time is 35min, the enzymolysis pH value is 4.5, and after enzymolysis, heating and reflux-extracting the enzymolysis solution for 1 time, reflux-extracting for 25min, and recovering the reflux-extracting solution to obtain reflux-extracting solution 2;
mixing the above obtained reflux extract 1, decoction, extract 2 and reflux extract 2, concentrating to obtain extract, drying at 40deg.C until water content is below 10%, and pulverizing to obtain the composition.
Example 5
The composition for treating obstructive sleep apnea-hypopnea syndrome described in example 1 was prepared by the following steps: the raw material herbs described in example 1 were pulverized by a polisher and then sieved with a 100-mesh sieve to obtain raw material powders.
The raw material powders were accurately weighed according to the amounts of the raw material flavors described in example 1, and the following procedure was performed:
Mixing astragalus, bighead atractylodes rhizome, dried orange peel and cimicifuga foetida to obtain a mixture 1, and mixing the mixture 1 with 40% ethanol solution according to the weight-to-volume ratio of 1g: mixing 8mL, performing reflux extraction for 0.5h 1 st time, adding 40% ethanol solution (according to the weight-volume ratio of the mixture 1 and the 40% ethanol solution of 1g:4 mL) into the extract of the retrieval flow, performing reflux extraction for 2 nd time, and extracting for 0.5h to obtain reflux extract 1;
mixing radix bupleuri, radix scutellariae, sun-dried ginseng, honey-fried licorice root and peppermint to obtain a mixture 2, and mixing the mixture 2 with water according to the weight-to-volume ratio of 1g: mixing 5mL, soaking for 20min, decocting, boiling, keeping boiling state for 18min, filtering, and collecting filtrate as decoction;
Mixing burdock, stiff silkworm, periostracum cicada, ligusticum wallichii and radix curcumae to obtain a mixture 3, and mixing the mixture 3 with water according to the weight-volume ratio of 1g: mixing 7mL, soaking for 20min, decocting, boiling for 25min, filtering, collecting filtrate, adding absolute ethanol until the concentration of ethanol solution is 50%, filtering to remove impurities, collecting filtrate, recovering ethanol to obtain extract 1, mixing extract 1 with absolute ethanol until the concentration of ethanol solution is 80%, filtering to remove impurities, collecting filtrate, and recovering ethanol to obtain extract 2;
Mixing rhizoma Acori Graminei, saviae Miltiorrhizae radix, purified pinellia Tuber, poria and radix Paeoniae alba to obtain mixture 4, mixing the mixture 4 with water and compound enzyme for enzymolysis (the mixture 4 comprises water: compound enzyme=1g: 8ml:0.08g, the weight ratio of cellulase and pectase in the compound enzyme is 1:2), the enzymolysis temperature is 35deg.C, the enzymolysis time is 30min, the enzymolysis pH value is 3.5, and after enzymolysis, heating and reflux-extracting the enzymolysis solution for 1 time, reflux-extracting for 20min, and recovering the reflux-extracting solution to obtain reflux-extracting solution 2;
Mixing the above obtained reflux extract 1, decoction, extract 2 and reflux extract 2, concentrating to obtain extract, drying at 45deg.C until water content is below 10%, and pulverizing to obtain the composition.
Example 6
The composition for treating obstructive sleep apnea-hypopnea syndrome described in example 1 was prepared by the following steps: the raw material herbs described in example 1 were pulverized by a polisher and sieved with a 50-mesh sieve to obtain raw material powders. The raw material powders were accurately weighed according to the amounts of the raw material flavors described in example 1, and the following procedure was performed:
Mixing astragalus, bighead atractylodes rhizome, dried orange peel and cimicifuga foetida to obtain a mixture 1, and mixing the mixture 1 with 50% ethanol solution according to the weight-to-volume ratio of 1g: mixing 12mL, performing 1 st reflux extraction for 1h, adding 50% ethanol solution (according to the weight-volume ratio of the mixture 1 and the 50% ethanol solution of 1g:6 mL), and performing 2 nd reflux extraction for 1h to obtain reflux extract 1;
Mixing radix bupleuri, radix scutellariae, sun-dried ginseng, honey-fried licorice root and peppermint to obtain a mixture 2, and mixing the mixture 2 with water according to the weight-to-volume ratio of 1g: mixing 8mL, soaking for 30min, decocting, boiling, keeping boiling state for 22min, filtering, and collecting filtrate as decoction;
mixing burdock, stiff silkworm, periostracum cicada, ligusticum wallichii and radix curcumae to obtain a mixture 3, and mixing the mixture 3 with water according to the weight-volume ratio of 1g: mixing 10mL, soaking for 30min, decocting, boiling for 40min, filtering, collecting filtrate, adding absolute ethanol until the concentration of ethanol solution is 60%, filtering, removing impurities, collecting filtrate, recovering ethanol to obtain extract 1, mixing extract 1 with absolute ethanol until the concentration of ethanol solution is 90%, filtering, removing impurities, collecting filtrate, and recovering ethanol to obtain extract 2;
Mixing rhizoma Acori Graminei, saviae Miltiorrhizae radix, purified pinellia Tuber, poria and radix Paeoniae alba to obtain mixture 4, mixing the mixture 4 with water and compound enzyme for enzymolysis (the mixture 4 comprises water: compound enzyme=1g: 10ml:0.08g, the weight ratio of cellulase and pectase in the compound enzyme is 1:2), the enzymolysis temperature is 45deg.C, the enzymolysis time is 50min, the enzymolysis pH value is 6.5, and after enzymolysis, heating and reflux-extracting the enzymolysis solution for 1 time, reflux-extracting for 30min, and recovering the reflux-extracting solution to obtain reflux-extracting solution 2;
mixing the above obtained reflux extract 1, decoction, extract 2 and reflux extract 2, concentrating to obtain extract, drying at 50deg.C until water content is below 10%, and pulverizing to obtain the composition.
Example 7
The composition for treating obstructive sleep apnea-hypopnea syndrome described in example 2 was prepared via the preparation process described in example 4.
Example 8
The composition for treating obstructive sleep apnea-hypopnea syndrome described in example 3 was prepared via the preparation process described in example 4.
Example 9
The composition prepared in example 4 and auxiliary materials (dextrin) are mixed according to the weight ratio of 1:1.5, and then a dry granulation method is adopted to obtain a granular preparation for treating obstructive sleep apnea hypopnea syndrome, and the granular preparation is packaged into bags (the composition in example 4 is used in an amount of 1 bag).
Example 10
The composition prepared in example 4 and auxiliary materials (dextrin) are mixed according to the weight ratio of 1:3, and then a dry granulation method is adopted to obtain a granular preparation for treating obstructive sleep apnea hypopnea syndrome, and the granular preparation is packaged into bags (the composition in example 4 is used in an amount of 1 bag).
Example 11
The composition prepared in example 4 and auxiliary materials (dextrin) are mixed according to the weight ratio of 1:2.5, and then a dry granulation method is adopted to obtain a granular preparation for treating obstructive sleep apnea hypopnea syndrome, and the granular preparation is packaged into bags (the composition in example 4 is used in an amount of 1 bag).
Example 12
The composition prepared in example 5 and auxiliary materials (dextrin) are mixed according to the weight ratio of 1:1.5, and then a dry granulation method is adopted to obtain the granular preparation for treating obstructive sleep apnea-hypopnea syndrome.
Example 13
The composition prepared in example 6 and auxiliary materials (dextrin) are mixed according to the weight ratio of 1:1.5, and then a dry granulation method is adopted to obtain the granular preparation for treating the obstructive sleep apnea-hypopnea syndrome.
Comparative example 1
The difference from example 1 is that the amounts of the raw materials in the composition are different, in particular: 18g of astragalus membranaceus, 10g of bighead atractylodes rhizome, 15g of dried orange peel, 10g of cimicifuga foetida, 9g of radix bupleuri, 6g of radix scutellariae, 6g of sun-dried ginseng, 10g of honey-fried licorice root, 3g of peppermint, 10g of burdock, 9g of stiff silkworm, 6g of cicada slough, 10g of ligusticum wallichii, 20g of radix curcumae, 15g of rhizoma acori graminei, 9g of radix salviae miltiorrhizae, 9g of rhizoma pinelliae preparata, 10g of poria cocos and 9g of radix paeoniae alba.
The preparation method adopts a water decoction extraction method:
Accurately weighing 19 medicinal materials according to the weight of each medicinal material in the comparative example, soaking the medicinal materials in water, adding 8 times of water, heating and reflux-extracting for 2 times, filtering the reflux extract of the two times, mixing filtrates, and concentrating into extract; the wet granulation method is adopted, and the material-to-material ratio is 1:1 adding auxiliary materials, granulating, drying at 60 ℃ to obtain preparation granules, and packaging into bags, wherein the amount is one bag.
Comparative example 2
The difference from comparative example 1 is that the preparation method described in example 4 was used to prepare a granular preparation according to the method of example 9, and the granular preparation was packaged in a bag in an amount of one bag.
Comparative example 3
The difference from example 1 is that the amount of astragalus membranaceus is 15g, the amount of sun-dried ginseng is 5g, and the rest is the same as example 1. The granular formulations obtained by the methods of example 4 and example 9 were packaged into bags in the amount of one bag.
Comparative example 4
The composition is the same as in example 1, and the preparation method is different from example 4 in that: the volume fraction of the ethanol solution used for reflux extraction of mixture 1 was 60%, the remainder being the same as in example 4. After obtaining the composition, a granular formulation was prepared by the method of example 9, and packaged into a bag in an amount of one bag.
Comparative example 5
The composition is the same as in example 1, and the preparation method is different from example 4 in that: when the mixture 2 is mixed with water, soaked and decocted, the boiling time is changed to 40min, and the rest is the same as in the example 4. After obtaining the composition, a granular formulation was prepared by the method of example 9, and packaged into a bag in an amount of one bag.
Comparative example 6
The composition is the same as in example 1, and the preparation method is different from example 4 in that: the extract 2 was obtained without two alcohol precipitation steps, the remainder being the same as in example 4. After obtaining the composition, a granular formulation was prepared by the method of example 9, and packaged into a bag in an amount of one bag.
Comparative example 7
The composition is the same as in example 1, and the preparation method is different from example 4 in that: no complex enzyme was added in the process of obtaining the reflux extract 2, and the rest was the same as in example 4. After obtaining the composition, a granular formulation was prepared by the method of example 9, and packaged into a bag in an amount of one bag.
Comparative example 8
The composition is the same as in example 1, and the preparation method is different from example 4 in that: in the process of obtaining the reflux extract 2, the weight ratio of the cellulase to the pectase in the added complex enzyme is 2:1 and the rest are the same as in example 4. After obtaining the composition, a granular formulation was prepared by the method of example 9, and packaged into a bag in an amount of one bag.
Example 14
180 Cases of OSAHS patients diagnosed in auxiliary hospitals of the university of vinca traditional Chinese medicine were collected from 1 month 2022 to 10 months 2023, and the inclusion criteria were: meets the diagnosis standard of the disease in the diagnosis and treatment guidelines (2011 revised edition) of obstructive sleep apnea-hypopnea syndrome, and divides the OS-AHS disease degree into light, moderate and severe according to the guidelines. Light: an Apnea Hypopnea Index (AHI) of 5-15 times/hour, an oxygen saturation (SpO 2) of 85-90%; and (3) moderately: AHI 16-30 times/hour, spO 2 80-84%; severe: AHI >30 times/hr, spO 2 <80%. The patients in the group 9 were administered the granule formulation of example 9 once a day, one bag, and the patients in the group 1 to 8 were administered the granule formulation of comparative examples 1 to 8 twice a day, one bag once a day. The 9 groups of sex, age, BMI, disease degree and the like are compared, and the difference has no statistical significance (P is more than 0.05) and has comparability. The study was approved by the ethical committee of affiliated hospitals at the university of vinca, and all subjects had signed the informed consent prior to the trial. Daytime sleepiness of patients was assessed using the Epworth sleepiness assessment table (Ep-worth sleepiness score, ESS): 0 to 9 minutes = normal, 10 to 13 minutes = mild, 14 to 19 minutes = moderate, 20 to 23 minutes = severe. For 15 days of continuous treatment, the daytime sleepiness of different groups before and after treatment is counted, SPSS26.0 software is used for processing statistical analysis, paired t test is adopted for comparison in groups, and independent sample t test is adopted for comparison between groups. The results are shown in Table 1.
Table 1 results of ESS score comparisons for different groups of obstructive sleep apnea-hypopnea syndrome patients
| Group of | Before treatment (separate) | After treatment (Branch) |
| Example 9 group | 16.52±3.21 | 9.42±2.11 |
| Comparative example 1 group | 14.28±4.32 | 13.11±3.21 |
| Comparative example 2 group | 15.31±2.42 | 12.12±2.02 |
| Comparative example 3 group | 14.98±3.11 | 11.82±1.23 |
| Comparative example 4 group | 15.61±2.78 | 11.68±1.42 |
| Comparative example 5 group | 14.66±3.14 | 10.89±2.43 |
| Comparative example 6 group | 15.01±2.02 | 12.02±1.13 |
| Comparative example 7 group | 14.78±3.68 | 12.04±1.51 |
| Comparative example 8 group | 15.58±2.57 | 11.65±2.32 |
As can be seen from table 1, the nine groups of ESS scores before treatment compare, are not quite different and are comparable. After treatment, the treatment effect was optimal for the group of example 9, and the effects were general for the remaining groups.
Example 15
Comparative example 9 the effect of the granule formulation and the yang-increasing and stomach-benefiting decoction formulation on treating OSAHS (obstructive sleep apnea hypopnea syndrome) was that the yang-increasing and stomach-benefiting decoction formulation consisted of 30g of astragalus mongholicus, 15g of pinellia ternate, 15g of ginseng, 15g of honey-fried licorice root, 9g of pubescent angelica root, 9g of divaricate saposhnikovia root, 9g of white peony root, 9g of notopterygium root, 6g of orange peel, 5g of poria cocos, 5g of bupleurum, 5g of alisma orientale, 5g of bighead atractylodes rhizome and 1.5g of coptis chinensis.
(1) Effects on intermittent hypoxia mouse serum HIF-1 alpha, IFN-gamma and IL-4 levels
After 48 male C57BL/6J healthy mice (weight 20-22 g) of 4 weeks old were adaptively fed for 3 days under specific pathogen-free conditions, the experimental mice were randomly divided into four groups, namely group A (blank: normoxic), group B (model group), group C (model+Yang-raising stomach-benefiting soup control group), and group D (model+example 9 pellet treatment group) of 12 mice each, according to the purpose of the study.
The group A mice are placed in a normoxic environment (the oxygen content concentration is 21%), the group B mice, the group C mice and the group D mice are placed in a closed oxygen cabin, an oxygen cabin switch is opened, the oxygen and nitrogen proportion is regulated, the oxygen concentration in the cabin is regulated to be 10%, the oxygen is kept for 8 hours, the normoxic environment in the oxygen cabin is recovered for 16 hours, and the molding is kept for 4 weeks. Molding success standard: after 2 weeks, the ELISA of each group detected the hemoglobin content, and the significant difference between group A and B, C, D was regarded as successful molding, and after 2 weeks of molding, 0.2mL of blood was collected from the orbital vein of the mice for detecting the molding result, and the results are shown in Table 2.
TABLE 2 variation of hemoglobin content in Whole blood of mice of each group after 2 weeks of modeling (x.+ -. SD)
Note that: compared with group A, P <0.05, P <0.01
Group a did not intervene. Group B was gavaged with 0.5mL distilled water 1 time a day after 2 weeks of molding. The daily dosing amount of the mice in the group C and the group D is calculated to be 2.73 g.kg -1 by conversion of the dosing amount of the reference experimental animals in the group C and the group D, and the two formulas in the group C and the group D are dissolved in distilled water for filling the stomach according to the proportion for 1 time a day. Therapeutic gastric lavage treatment is performed in synchronization with molding for 2 weeks.
After molding for 4 weeks, food is not put in after 8:00 of night, 4 groups of animals are weighed and recorded according to serial numbers in 8:00 of the next morning, sodium pentobarbital (50 mg.kg -1) is used for intraperitoneal injection anesthesia, abdominal aorta blood collection is carried out after the anesthesia is successful, about 0.8mL of blood is collected by a 1.5mL centrifuge tube, the mixture is placed at room temperature for 3 hours, centrifuged by a 8000 r.min -1 centrifuge for 10 minutes (with a centrifugal radius of 6 cm), upper serum is collected, and the mixture is split into 1.5mL centrifuge tubes for preservation in a refrigerator at the temperature of minus 80 ℃ to be tested. HIF-1. Alpha., IFN-gamma. And IL-4 levels in serum were detected by ELISA kit.
The HIF-1. Alpha., IFN-gamma., IL-4 levels in the serum of each group of mice are shown in FIG. 1. Compared with the group A, the concentration of HIF-1 alpha in the serum of the mice in the group B, the group C and the group D is obviously increased, and the successful modeling is further verified. Compared with the group B, the serum of the group C and the group D has obviously reduced concentration of HIF-1 alpha, IFN-gamma and IL-4, which proves that the two have clinical significance for treating OSAHS by reducing the concentration level of HIF-1 alpha, IFN-gamma and IL-4. Meanwhile, the reduction degree of HIF-1 alpha, IFN-gamma and IL-4 concentration in the serum of the group D mice is obviously higher than that of the group C, which proves that the particle formula has a better treatment effect compared with the traditional decoction formula.
(2) Effect on NF- κB expression in nasal mucosal tissue of intermittent hypoxic mice
The molding process and animal grouping process are the same as the above (1).
After molding for 4 weeks, no more food was given at night 8:00, four groups of animals were weighed and recorded on the next morning 8:00 according to serial number, anesthetized with pentobarbital sodium (50 mg/kg) for intraperitoneal injection, and sacrificed by bleeding. Group A, group B, group C and group D were randomly selected from 6 mice, the connection line between the two ears of the mice was used as incision, the connective tissues such as the fur and muscle of the head of the mice were peeled off by using an ophthalmic scissors, the nose was always exposed, the mandible and teeth were removed by using a mouse rongeur scissors, the whole nose was cut off together with the nasal septum, and the mixture was placed in 4% paraformaldehyde at 4℃overnight. The rest 6 mice in the group A, the group B, the group C and the group D use the connecting line between two ears of the mice as an incision, use ophthalmic scissors to peel connective tissues such as head fur and muscle of the mice, always peel and expose nasal septum, use ophthalmic scissors to cut the nasal septum, use forceps to peel the nasal septum mucosa, put into liquid nitrogen for quick freezing, and then transfer into a refrigerator at the temperature of minus 80 ℃ for preservation. The whole stripping process needs to be carefully and slowly carried out, and the nasal septum membrane can not be scratched.
Taking a mouse nasal mucosa tissue, decalcifying, dehydrating, trimming, embedding and slicing, dewaxing to water by using dimethylbenzene and gradient ethanol, performing antigen retrieval, and putting the slice into 3% hydrogen peroxide for 10 minutes at room temperature; PBS washes 3 times, each for 5 minutes, blocking endogenous peroxidase, dripping primary antibody after serum sealing, standing overnight at 4 ℃, washing 3 times by PBS, each for 5 minutes, dripping secondary antibody, repeating PBS washing 3 times, preparing fresh DAB chromogenic liquid, dripping onto tissues, developing at room temperature, controlling the chromogenic time under a microscope, positively generating brown yellow, washing slices by distilled water to stop the chromogenic, counterstaining for 3 minutes by hematoxylin, washing by running water after blue return by clear water, dehydrating by gradient ethanol, transparency by dimethylbenzene, and sealing by neutral resin. The microscopic imaging system performs image acquisition on the sections, and the positive area ratio (% DAB Positive Tissue) of each image is calculated by using a Halo data analysis system. The results are shown in FIG. 2.
10-20 Mg of mouse nasal mucosa tissue is taken and placed in a mortar, total RNA is extracted, a reverse transcription reaction system is configured for reverse transcription, each reagent is sequentially added, and the mixture is placed on a PCR instrument for reaction. The experiment calculates the relative mRNA expression level of NF- κB in the nasal mucosa of mice at 2 －△△CT and purifies the mRNA expression level at ULTRAPAGE. The results are shown in FIG. 3.
NF- κB is present in the cytoplasm and normally is in an inactive state and is activated by upstream molecules and plays a key role in regulating a number of pathophysiological processes such as immune response, inflammatory response, cell differentiation, proliferation and apoptosis. As can be seen from FIGS. 2 and 3, the protein content and the relative mRNA expression level of NF- κB in the model group were higher than those in the blank group, while the protein content and the relative mRNA expression level of NF- κB in the administration group were lower than those in the model group, indicating that the administration group was effective in regulating NF- κB expression. Meanwhile, the protein content and the relative expression quantity of mRNA of NF- κB in the group D are lower than those in the group C, which shows that the inhibition effect of the particles to NF- κB in nasal mucosa is stronger than that of the traditional decoction, and the particles of the invention have better anti-inflammatory effect by inhibiting the expression of NF- κB in the nasal mucosa.
Example 16
Acute toxicity test of the particles described in example 9
SD rats were individually numbered and input into Excel form, and random numbers were generated by a computer to group 10 rats each, which were a blank group (distilled water), a low (1 g/kg) medium (2.3 g/kg) high dose group (4.6 g/kg) pellet of example 9, and after 12 hours of no water feeding, were administered by single gastric lavage, 0.2ml/10g each time, and the rats were observed for general conditions (body weight, diet, fur, behavior, secretion, excrement, etc.) and poisoning and death conditions, and continuously observed for 14 days. Rats feeding and body weight changes were recorded before dosing (day 0), on days 7 and 14 post dosing. The specific results are shown in fig. 4 and 5.
As can be seen from fig. 4 and 5, compared with the blank group, rats still respond to external stimulus after administration, and no death phenomenon occurs after administration for 14 days, so that the body weight is gradually increased, and the food intake is not obviously different from that of the blank group. In addition, the rats of the particle group of the invention have normal appearance, have no phenomena of activity reduction, somnolence, contracture, hair loosening and the like, have no abnormal secretion in eyes, ears, mouths and noses, and show that the particles of the invention have no obvious acute toxic reaction to the rats.
Example 17
Clinical study of the particles described in example 9
Diagnosis and treatment scheme
(1) Disease pattern typing for treatment of disease: spleen yang deficiency and phlegm stasis obstructing the collaterals
(2) Diagnosis of traditional Chinese medicine: refer to "the consensus of snoring's medical science and expertise" (journal of Chinese medical information, 2019).
(3) Western diagnosis: reference is made to guidelines for diagnosis and treatment of obstructive sleep apnea-hypopnea syndrome (basal edition) (2015).
(4) Reference standard for clinical cure or efficacy
Curative effect observation indexes:
Related symptoms: snoring during sleep, listlessness, debilitation, spontaneous perspiration, pharyngeal discomfort, limb heaviness, hypomnesis, stomach and abdomen discomfort, frequent urination, non-shaping or viscous stool, pale tongue with slippery or greasy coating, tortuosity of the tongue bottom, soft and thin pulse, weakness or smoothness of pulse. The main symptoms and the secondary symptoms are respectively assigned 0, 2, 4 and 6 according to the symptoms of no symptom, light symptom, medium symptom and heavy symptom; 0.1, 2 and 3 minutes.
The efficacy standard refers to the standard of "guidelines for diagnosis and treatment of obstructive sleep apnea-hypopnea syndrome (basic edition) (2015).
Symptom score decrease index = (pre-treatment score-post-treatment score)/pre-treatment score x 100%
Invalidation: the symptoms and signs are not obviously improved or even aggravated, and the integral of symptoms and signs is reduced by less than or equal to 30 percent;
The method is effective: the symptoms and signs are all obvious, the integral of symptoms and signs is reduced by more than 30 percent, but less than or equal to 70 percent;
the effect is shown: the symptom signs are obviously improved, the integral of symptoms is reduced by more than 70 percent, but less than or equal to 95 percent;
Clinical recovery: the symptoms diminish or substantially diminish in sign; the integral of syndrome is reduced by more than 95%.
(5) Statistical analysis of clinical cases
Patients with the 2018-2022 visit were collected and the patient information summary table is shown in table 3. The patient information summary table mainly provides basic patient information, prescription changes, combined medication and concomitant medication, adverse reactions, return visits (1 represents return visit 1 time, 2 represents return visit 2 times), or return visits, etc. Each patient took the granules of example 9 once a day, one bag at a time, with 7 days as a course of treatment. The results show (table 3) the number of observations: 100 cases; cure example 20; display case 50; effective example 22; in the case of invalid example 8, the total effective rate is 92%. No adverse reaction was observed.
Table 3 patient information table
/>
/>
/>
/>
/>
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. A composition for treating obstructive sleep apnea hypopnea syndrome, said composition comprising: 5-10 g of astragalus root, 1-3 g of bighead atractylodes rhizome, 1-2 g of dried orange peel, 3-8 g of cimicifuga rhizome, 3-6 g of bupleurum root, 3-5 g of baikal skullcap root, 2-4 g of sun-dried ginseng, 2-4 g of honey-fried licorice root, 1-4 g of peppermint, 2-6 g of burdock, 2-8 g of stiff silkworm, 2-4 g of cicada slough, 1-4 g of szechuan lovage rhizome, 4-8 g of radix curcumae, 5-10 g of grassleaf sweelflag rhizome, 2-6 g of red sage root, 2-5 g of purified pinellia tuber, 1-4 g of poria cocos and 1-4 g of white paeony root.
2. A method of preparing the composition of claim 1, comprising the steps of: mixing astragalus, bighead atractylodes rhizome, dried orange peel and cimicifuga foetida to obtain a mixture 1, mixing the mixture 1 with 40-50% ethanol solution by volume fraction, and carrying out reflux extraction to obtain a reflux extract 1;
Mixing radix bupleuri, radix scutellariae, sun-dried ginseng, honey-fried licorice root and mint to obtain a mixture 2, mixing and soaking the mixture 2 with water, then decocting, keeping boiling for 15-25 min, filtering and taking filtrate as decoction;
Mixing burdock, stiff silkworm, cicada slough, ligusticum wallichii and radix curcumae to obtain a mixture 3, mixing and soaking the mixture 3 with water, then decocting, keeping boiling for 30-40 min, filtering, taking filtrate, adding absolute ethyl alcohol until the concentration of an ethanol solution is 50-60%, filtering to remove impurities, taking filtrate to recover ethanol to obtain an extract 1, mixing the extract 1 with absolute ethyl alcohol until the concentration of the ethanol solution is 80-90%, filtering to remove impurities, and taking filtrate to recover ethanol to obtain an extract 2;
Mixing rhizoma Acori Graminei, saviae Miltiorrhizae radix, purified pinellia Tuber, poria and radix Paeoniae alba to obtain mixture 4, mixing the mixture 4 with water and complex enzyme for enzymolysis, heating and reflux extracting the enzymolysis solution to obtain reflux extract 2; the complex enzyme consists of cellulase and pectase;
mixing the reflux extract 1, decoction, extract 2 and reflux extract 2, concentrating to obtain extract, drying, and pulverizing to obtain the composition.
3. The preparation method according to claim 2, wherein the weight-to-volume ratio of the mixture 1 to the ethanol solution with the volume fraction of 40% -50% is 1g: 8-12 mL.
4. The method according to claim 2, wherein the soaking time is 20min to 30min.
5. The preparation method according to claim 2, wherein the weight-to-volume ratio of the mixture 2 to water is 1g: 5-8 mL, wherein the weight-volume ratio of the mixture 3 to water is 1g: 7-10 mL.
6. The preparation method according to claim 2, wherein the temperature of the enzymolysis is 35-45 ℃, the time of the enzymolysis is 30-50 min, and the pH value of the enzymolysis is 3.5-6.5.
7. The preparation method according to claim 2, wherein the amount of the complex enzyme is 0.06g-0.09g per 1g of the mixture 4, and the weight ratio of the cellulase to the pectase is 1:2-3.
8. A granular formulation for the treatment of obstructive sleep apnea hypopnea syndrome, said granular formulation consisting of a composition according to claim 1 and an adjuvant.
9. The granule formulation as claimed in claim 8, wherein the weight ratio of the composition to the auxiliary material is 1:1.5 to 3.
10. A method of preparing a granular formulation according to claim 8 or 9, comprising the steps of: and mixing the composition with auxiliary materials, and performing dry granulation to obtain the granular preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410223559.4A CN118078942A (en) | 2024-02-28 | 2024-02-28 | Composition and granule preparation for treating obstructive sleep apnea-hypopnea syndrome and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410223559.4A CN118078942A (en) | 2024-02-28 | 2024-02-28 | Composition and granule preparation for treating obstructive sleep apnea-hypopnea syndrome and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118078942A true CN118078942A (en) | 2024-05-28 |
Family
ID=91164318
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410223559.4A Pending CN118078942A (en) | 2024-02-28 | 2024-02-28 | Composition and granule preparation for treating obstructive sleep apnea-hypopnea syndrome and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118078942A (en) |
-
2024
- 2024-02-28 CN CN202410223559.4A patent/CN118078942A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104491801A (en) | Traditional Chinese medicine preparation for treating acute or chronic gastritis and preparation method thereof | |
| CN103385993B (en) | Chinese medicine preparation for treating gastric ulcer and preparation method thereof | |
| CN112972635B (en) | A Chinese medicinal composition for treating chronic kidney diseases and chronic renal failure | |
| CN104491802A (en) | Application of traditional Chinese medicine preparation in preparation of medicine for treating acute or chronic gastritis | |
| CN115252753B (en) | Traditional Chinese medicine composition for treating insomnia and application thereof | |
| CN111214637A (en) | Traditional Chinese medicine composition and preparation method and medicinal application thereof | |
| CN110339276A (en) | Traditional Chinese medicine for treating digestive tract tumor and preparation method thereof | |
| CN102430097A (en) | Chinese medicine for treating vitiligo | |
| CN105641419A (en) | Traditional Chinese medicine composition for treating Yin deficiency type cough caused by lung cancer | |
| CN101327293B (en) | Capsules for treating peptic ulcer and preparation method thereof | |
| CN118078942A (en) | Composition and granule preparation for treating obstructive sleep apnea-hypopnea syndrome and preparation method thereof | |
| CN103585515A (en) | Effervescing agent medicament for treating children alimentary anemia | |
| CN108355124B (en) | Traditional Chinese medicine composition for treating airway mucus hypersecretion and application thereof | |
| CN107158286B (en) | Traditional Chinese medicine composition for treating respiratory tract injury induced symptoms caused by haze and preparation method thereof | |
| CN105250968A (en) | Traditional Chinese medicine preparation for treating asthma | |
| CN116211993B (en) | Composition for treating senile chronic disease and its preparation method | |
| CN112168931B (en) | A pharmaceutical composition for treating oral ulcer, and its preparation method | |
| CN115869375B (en) | Traditional Chinese medicine composition for clearing heat and dispelling wind as well as preparation method and application thereof | |
| JPH0733676A (en) | Composition for lowering blood suger value | |
| CN116688053B (en) | Traditional Chinese medicine composition for improving tumour cachexia and muscular atrophy, preparation method and application | |
| CN115998824B (en) | Traditional Chinese medicine composition for clearing damp and detoxicating, and preparation method and application thereof | |
| CN112138105B (en) | Traditional Chinese medicine composition for treating bronchiectasis lung-spleen qi deficiency and phlegm-damp lung blocking syndrome and application thereof | |
| CN101264202B (en) | Hericium erinaceus digestion-promoting Chinese medicinal composition and preparation thereof | |
| CN1515275A (en) | Chinese medicine composition with action of nourishing lung, curing cough and relieving asthma | |
| CN105311419A (en) | Traditional Chinese medicine composition for treating oral inflammations and preparation method thereof |
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 |