CN116492359A - Composition containing glycosylated puerarin and preparation method and application thereof - Google Patents
Composition containing glycosylated puerarin and preparation method and application thereof Download PDFInfo
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- CN116492359A CN116492359A CN202310381943.2A CN202310381943A CN116492359A CN 116492359 A CN116492359 A CN 116492359A CN 202310381943 A CN202310381943 A CN 202310381943A CN 116492359 A CN116492359 A CN 116492359A
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- Prior art keywords
- puerarin
- glycosylated
- composition
- tmao
- preparation
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- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical class O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 title claims abstract description 118
- 239000000203 mixture Substances 0.000 title claims abstract description 62
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 claims abstract description 43
- PAFLSMZLRSPALU-UHFFFAOYSA-N Salvianic acid A Natural products OC(=O)C(O)CC1=CC=C(O)C(O)=C1 PAFLSMZLRSPALU-UHFFFAOYSA-N 0.000 claims abstract description 40
- RXUWDKBZZLIASQ-UHFFFAOYSA-N Puerarin Natural products OCC1OC(Oc2c(O)cc(O)c3C(=O)C(=COc23)c4ccc(O)cc4)C(O)C(O)C1O RXUWDKBZZLIASQ-UHFFFAOYSA-N 0.000 claims abstract description 30
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 15
- 241001061264 Astragalus Species 0.000 claims abstract description 13
- 235000006533 astragalus Nutrition 0.000 claims abstract description 13
- 229930182490 saponin Natural products 0.000 claims abstract description 13
- 150000007949 saponins Chemical class 0.000 claims abstract description 13
- 210000004233 talus Anatomy 0.000 claims abstract description 13
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims abstract description 12
- 208000035868 Vascular inflammations Diseases 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- SMDOOINVMJSDPS-UHFFFAOYSA-N Astragaloside Natural products C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)=C1 SMDOOINVMJSDPS-UHFFFAOYSA-N 0.000 abstract description 7
- QMNWISYXSJWHRY-XWJCTJPOSA-N astragaloside Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)C4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)CC3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-XWJCTJPOSA-N 0.000 abstract description 7
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 4
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- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 7
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000011740 C57BL/6 mouse Methods 0.000 description 4
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- 238000010172 mouse model Methods 0.000 description 4
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 3
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- 241000699666 Mus <mouse, genus> Species 0.000 description 3
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- 230000018109 developmental process Effects 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
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- 235000011073 invertase Nutrition 0.000 description 3
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- 210000002784 stomach Anatomy 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
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- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 2
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- 241000699670 Mus sp. Species 0.000 description 2
- 244000046146 Pueraria lobata Species 0.000 description 2
- 235000010575 Pueraria lobata Nutrition 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
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- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000643 oven drying Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- 229940127355 PCSK9 Inhibitors Drugs 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
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- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
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- 239000008346 aqueous phase Substances 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229960001838 canakinumab Drugs 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
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- 230000034994 death Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 235000018927 edible plant Nutrition 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000007654 ischemic lesion Effects 0.000 description 1
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 1
- 235000008696 isoflavones Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
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- 230000001737 promoting effect Effects 0.000 description 1
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- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
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
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses a composition containing glycosylated puerarin, a preparation method and application thereof, wherein the composition comprises glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragaloside; the mass ratio of the glycosylated puerarin to the beta- (3, 4-dihydroxyphenyl) lactic acid to the astragalus saponin is 1-2:2-4:3-5; the glycosylated puerarin is mono-glycosylated puerarin or oligosaccharyl puerarin. The puerarin is glycosylated, so that the puerarin can be absorbed in vivo conveniently, the TMAO in the intestinal tract can be effectively removed, and the puerarin extract with dual functions of nutrition and medicine has the function of removing the TMAO, and simultaneously eliminates vascular inflammation caused by the TMAO, and has the function of relieving atherosclerosis diseases.
Description
Technical Field
The invention relates to the field of medicine preparation, in particular to a composition containing glycosylated puerarin, a preparation method and application thereof.
Background
Atherosclerosis has a high prevalence and is a major public health problem that humans must face now and in the future. The atherosclerosis mainly involves large and medium-sized elastic arteries such as coronary arteries and carotid arteries, so that the wall of a blood vessel is thickened and hardened, and the lumen is narrow, and finally ischemic lesions of corresponding tissues and organs are caused. Atherosclerosis is a result of the comprehensive development of a variety of factors, including lipid metabolism disorders, inflammatory reactions, endothelial damage, vascular aging, etc., and the specific pathogenesis is not completely understood. The current methods of treating atherosclerosis are mainly to use statins to reduce the blood lipid level of patients, however, even on the basis of optimal lifestyle intervention and high-dose statin treatment, the mortality of patients is still high after the addition of novel lipid lowering agents such as PCSK9 inhibitors and CETP inhibitors, even after the addition of Canakinumab anti-inflammatory treatment. Therefore, searching for a new therapeutic strategy has important significance in reducing the prevalence and mortality of cardiovascular and cerebrovascular diseases.
More and more researches find that intestinal flora is closely related to the occurrence and development of atherosclerosis and becomes a new target for preventing and treating the atherosclerosis. Studies have found that there is a significant difference in intestinal flora structure between atherosclerotic patients and healthy people. Intestinal flora metabolizes dietary choline, betaine, and L-carnitine to trimethylamine oxide (trimethylamine oxide, TMAO). TMAO, an important metabolite of the intestinal flora, promotes vascular inflammation and thus participates in the development and progression of atherosclerosis, and predicts the long-term risk of death of cardiovascular diseases independently of conventional risk factors. Obviously, the increased amount of TMAO, a metabolic product of the intestinal flora, increases the risk of atherosclerosis in the body. Thus, finding and developing a safe and effective functional food to clear TMAO is of great importance in reducing the risk of atherosclerosis.
The kudzuvine root is a medicinal and edible plant with the characteristic of Ling nan, has the reputation of 'southern ginseng', and has obvious protective effect on cardiovascular. Puerarin is the main active substance of radix Puerariae, and has the advantages of safety, effectiveness, small toxic and side effects, mass purification, etc. However, puerarin has indissolvable property and relatively difficult absorption, and most of puerarin is discharged along with feces after oral administration, and the rest of puerarin is absorbed by human body, so that the curative effect is not ideal. The puerarin is required to be efficiently absorbed in the intestinal tract when acting on the metabolic product TMAO of the intestinal flora, the existing composition has relatively poor effect, and the medicinal requirement cannot be met.
Disclosure of Invention
The invention provides a composition containing glycosylated puerarin, a preparation method and application thereof, and aims to solve the defects in the prior art.
The invention firstly provides a composition containing glycosylated puerarin, which comprises glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragaloside; the mass ratio of the glycosylated puerarin to the beta- (3, 4-dihydroxyphenyl) lactic acid to the astragalus saponin is 1-2:2-4:3-5; the glycosylated puerarin is mono-glycosylated puerarin or oligosaccharyl puerarin.
The invention also provides the following optimization scheme:
preferably, the mass ratio of the glycosylated puerarin, the beta- (3, 4-dihydroxyphenyl) lactic acid and the astragaloside is 2:2:3.
Preferably, the preparation of the glycosylated puerarin adopts glycosylase to biologically transform puerarin.
Preferably, the composition is a tablet, a capsule preparation, a granule, a pill, an oral liquid or an injection.
Preferably, the composition further comprises a pharmaceutically acceptable carrier.
The invention also provides a preparation method of the composition containing glycosylated puerarin, which comprises the following steps:
s1, biologically converting puerarin into glycosylated puerarin by glycosylase;
s2, drying and crushing glycosylated puerarin at 50-60 ℃;
s3, mixing glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragalus saponin according to the mass ratio of 1-2:2-4:3-5 to obtain the composition.
The invention also discloses application of the composition containing glycosylated puerarin in preparation of a medicament for reducing TMAO content.
The invention also discloses application of the composition containing glycosylated puerarin in preparation of a medicament for treating vascular inflammation.
The invention also discloses application of the composition containing glycosylated puerarin in preparation of medicines for treating and/or preventing atherosclerosis.
The puerarin is glycosylated, so that the puerarin can be absorbed in vivo conveniently, the TMAO in the intestinal tract can be effectively removed, and the puerarin extract with dual functions of nutrition and medicine has the function of removing the TMAO, and simultaneously eliminates vascular inflammation caused by the TMAO, and has the function of relieving atherosclerosis diseases.
The invention can act on TMAO in intestinal tract and remove it, and can be used for developing medicines, health products, nourishment, foods and beverages, etc., with good social and economic benefits.
Drawings
FIG. 1 is a table showing the effect of the experimental groups 1-6 and the control groups 7-9 on TMAO content according to the invention;
FIG. 2 is a graph showing the effect of the composition of the present invention on plasma TMAO in a mouse model of atherosclerosis;
FIG. 3 is a graph of the component content of a composition of the present invention versus TMAO-induced macrophage inflammatory response;
FIG. 4 is a graph showing the effect of compositions of the present invention on the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta);
FIG. 5 is a graph showing the effect of compositions of the present invention on the levels of the pro-inflammatory factors interleukin-4 (IL-4), and pro-inflammatory factor interleukin-6 (IL-6);
FIG. 6 is a Western blot of the adhesion-related molecules ICAM-1, VCAM-1 and GAPDH for aortic root in experimental group 4 of the present invention;
FIG. 7 is a graph showing the inhibition of ICAM-1, VCAM-1 by Experimental group 4 of the present invention;
FIG. 8 is a graph showing the effect of experimental group 4 of the present invention on IL-6, IL-1. Beta. And TNF-. Alpha.content.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments thereof in order to enable those skilled in the art to better understand the technical aspects of the invention.
The composition containing glycosylated puerarin comprises glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragaloside; the mass ratio of the glycosylated puerarin to the beta- (3, 4-dihydroxyphenyl) lactic acid to the astragalus saponin is 1-2:2-4:3-5; the glycosylated puerarin is mono-glycosylated puerarin or oligosaccharyl puerarin.
Glycosylation of puerarin the preparation of the glycosylated puerarin adopts the biological conversion of the glycosylase to prepare the puerarin, and preferably adopts the aqueous phase conversion, 0.1-1g of puerarin is added into a fermentation bottle, water is added to 1L and the puerarin is uniformly shaken, then a buffering agent is added, and then the invertase is added for conversion, so that the glycosylated puerarin is obtained.
And purifying and drying the glycosylated puerarin to obtain a glycosylated puerarin finished product.
And mixing glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragaloside according to the mass ratio of 1-2:2-4:3-5, and adding surfactant, carrier, excipient, disintegrating agent and the like to prepare the finished product medicine.
In a better proportion, the mass ratio of the glycosylated puerarin, the beta- (3, 4-dihydroxyphenyl) lactic acid and the astragalus saponin is 2:2:3.
Preferably, the composition is a tablet, a capsule preparation, a granule, a pill, an oral liquid or an injection.
Preferably, the composition further comprises a pharmaceutically acceptable carrier.
The invention also provides a preparation method of the composition containing glycosylated puerarin, which comprises the following steps:
s1, biologically converting puerarin into glycosylated puerarin by glycosylase;
the preparation method comprises the steps of adopting water phase conversion, adding 0.1-1g of puerarin into a fermentation bottle, adding water to 1L, shaking uniformly, adding a buffering agent, adding invertase for conversion, and converting into glycosylated puerarin.
S2, drying and crushing glycosylated puerarin at 50-60 ℃;
purifying glycosylated puerarin, drying and pulverizing into powder; drying may be oven drying or spray drying.
S3, mixing glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragalus saponin according to the mass ratio of 1-2:2-4:3-5 to obtain the composition.
The composition containing glycosylated puerarin is applied to preparation of medicines for reducing TMAO content.
The composition containing glycosylated puerarin is applied to the preparation of medicaments for treating vascular inflammation.
The composition containing glycosylated puerarin is applied to the preparation of medicines for treating and/or preventing atherosclerosis.
Puerarin is an isoflavone compound, has relative molecular weight of 416.37, is mainly extracted from root of leguminous plant, and is mainly used for treating coronary heart disease, angina pectoris and hypertension clinically. The flavone in the kudzuvine root can increase the blood flow of the brain and the artery, has a promoting effect on the blood circulation of animals, can effectively improve the vascular tension and the elasticity, can improve the blood circulation and can effectively remove the blood stasis.
Beta- (3, 4-dihydroxyphenyl) lactic acid is white needle crystal, is a phenolic aromatic acid compound, and has obvious effects of reducing blood fat, dilating blood vessels, increasing arterial blood flow, and resisting coagulation and thrombus.
The astragaloside is colorless needle-like crystal, has molecular weight of 784.97 and molecular formula of C41H68O14, can increase the number of erythrocytes, leukocytes and platelets, can prevent and treat the decrease of exogenic leukocytes and bone marrow nucleated cells caused by radiation, promote the differentiation and proliferation of hematopoietic stem cells, and prevent the decrease of phagocytic function of macrophages caused by irradiation.
The invention mainly carries out effective proportion on glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragalus saponin, and solves the defects that the medicines in the prior art have insufficient effect on the metabolic product TMAO of intestinal flora and cannot effectively remove the metabolic product TMAO of intestinal flora. The invention mainly utilizes the mixture of glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragaloside to increase the solubility of the glycosylated puerarin, optimize the activity of the glycosylated puerarin in the stomach and intestine and increase the cleaning function of the glycosylated puerarin on the metabolic product TMAO of intestinal flora.
The foregoing is a summary of the invention and is described below in conjunction with specific embodiments.
1. Preparation of compositions containing glycosylated puerarin
The preparation method of the composition containing glycosylated puerarin in the embodiment comprises the following steps:
s1, biologically converting puerarin into glycosylated puerarin by glycosylase; the glycosylated puerarin is mono-glycosylated puerarin or oligosaccharyl puerarin;
the preparation method comprises the steps of adopting water phase conversion, adding 0.1-1g of puerarin into a fermentation bottle, adding water to 1L, shaking uniformly, adding a buffering agent, adding invertase for conversion, and converting into glycosylated puerarin.
S2, drying and crushing glycosylated puerarin at 50-60 ℃;
purifying glycosylated puerarin, drying and pulverizing into powder; drying may be oven drying or spray drying.
S3, mixing glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragalus saponin according to the mass ratio of 1-2:2-4:3-5 to obtain the composition.
The components were mixed according to the mass ratios of the glycosylated puerarin in S3, beta- (3, 4-dihydroxyphenyl) lactic acid and Astragalus saponins, and the components were mixed according to Table 1. The mono-glycosylated puerarin is used in table 1.
Table 1 detailed composition table of experimental and control groups
2. Effect of the composition of the present invention on plasma TMAO in mice model of atherosclerosis
The specific method comprises the following steps:
(1) In the detection experiment, a high-fat high-cholesterol (18% fat, 1.2% cholesterol) is adopted to construct an atherosclerosis mouse model, and the effect of puerarin on the plasma TMAO of the atherosclerosis mouse model is observed. All ApoE-/-mice were randomly divided into three groups, six in each of the normal control group and the model group, and the glycosylated puerarin-containing composition intervention group was set up as experimental groups 1-6 and control groups 7-9, 6 per experimental group or control group. Experimental grouping: normal control group (normal feed), model group (high-fat high-cholesterol feed), and intervention group (stomach lavage of 200mg/kg of composition containing glycosylated puerarin based on high-fat high-cholesterol feed).
(2) After 3 months of intervention as described above, plasma was collected from each group of ApoE-/-mice and the TMAO content was examined to give Table 2.
| TMAO concentration (um) | |
| Experiment group 1 | 1.02 |
| Experiment group 2 | 0.83 |
| Experiment group 3 | 0.65 |
| Experiment group 4 | 0.43 |
| Experiment group 5 | 0.78 |
| Experiment group 6 | 0.58 |
| Control group 7 | 1.2 |
| Control group 8 | 1.11 |
| Control group 9 | 1.15 |
TABLE 2 detection of TMAO content in mouse plasma
The effect of groups 1-6 and control groups 7-9 on TMAO levels in mouse plasma is shown in FIG. 1, where it can be seen that TMAO levels in group 4 are the lowest and therefore the effect on TMAO removal is optimal. Fig. 2 is a comparison of parameters of experimental group 4, normal control group and model group, and it can be seen from fig. 2 that the normal control group has the lowest TMAO content in mice and the model group has the highest TMAO content in mice, and the composition of experimental group 4 of the present invention has a significant effect on TMAO content and a significant decrease in TMAO content.
3. Effect of the inventive composition on TMAO-induced macrophage inflammatory response
The specific method comprises the following steps:
(1) In the detection experiment, exogenous TMAO is adopted to stimulate mouse mononuclear macrophage RAW264.7, and the effect of the composition containing glycosylated puerarin on TMAO-induced inflammatory response of a cell model is observed. Experimental grouping: normal control group, model group (TMAO, 100. Mu. Mol/L), composition group containing glycosylated puerarin (TMAO concentration is 100. Mu. Mol/L, composition containing glycosylated puerarin concentration is 50 mg/L), and experiment group 4-6 were selected for carrying out experiment of composition group containing glycosylated puerarin. The cell culture medium is randomly divided into three groups, namely four culture media in each of a normal control group and a model group, the group containing the glycosylated puerarin composition is arranged according to the experimental groups 4-6, and four culture media are also arranged in each of the experimental groups 4-6. As shown in fig. 3, cell viability was tested and consistent for each group.
(2) After 24 hours of intervention as described above, the culture supernatants of each group of cells were collected and Elisa tested for the amounts of the pro-inflammatory factors interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor- α (TNF- α) and averaged for each group of tested data to give FIGS. 4 and 5. As can be seen from FIGS. 4 and 5, the composition of the present invention has a significant effect on tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), pro-inflammatory factor interleukin-4 (IL-4), pro-inflammatory factor interleukin-6 (IL-6).
4. Effects of glycosylated puerarin-containing composition on TMAO-induced C57BL/6 mouse aortic inflammatory reaction
(1) In the test, exogenous TMAO is adopted to stimulate a C57BL/6 mouse, and the effect of the composition of the invention on the aortic inflammatory response induced by TMAO is observed. All the C57BL/6 mice were randomly divided into three groups of six in each of the normal control group and the model group, and the group containing the glycosylated puerarin composition was set up according to the experimental group 4, and 6 were set up. Experimental grouping: normal control group, model group (0.12% added to drinking water), glycosylated puerarin-containing composition group (200 mg/kg of glycosylated puerarin-containing composition was infused into stomach on the basis of 0.12% tmao drinking water).
(2) After 8 weeks of the above intervention, the aorta of each group of C57BL/6 mice was collected, and the aortic root adhesion-related molecules ICAM-1, VCAM-1 were examined by Western blotting, and the levels of the pro-inflammatory factors IL-6, IL-1. Beta. And TNF-. Alpha.were examined by Elisa.
As can be seen from FIGS. 6-8, the composition of the present invention has a remarkable inhibitory effect on ICAM-1 and VCAM-1, substantially flush with the normal control group, and is effective in improving aortic root adhesion. The compositions of the invention also provide significant improvements in IL-6, IL-1. Beta. And TNF-alpha. Levels, particularly TNF-alpha levels even lower than normal control levels.
The foregoing is merely a preferred embodiment of the present invention, and it should be noted that the above-mentioned preferred embodiment should not be construed as limiting the invention, and the scope of the invention should be defined by the appended claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and such modifications and adaptations are intended to be comprehended within the scope of the invention.
Claims (9)
1. A composition comprising glycosylated puerarin, characterized in that: comprises glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragalus saponin; the mass ratio of the glycosylated puerarin to the beta- (3, 4-dihydroxyphenyl) lactic acid to the astragalus saponin is 1-2:2-4:3-5; the glycosylated puerarin is mono-glycosylated puerarin or oligosaccharyl puerarin.
2. The glycosylated puerarin-containing composition according to claim 1, characterized in that: the mass ratio of the glycosylated puerarin to the beta- (3, 4-dihydroxyphenyl) lactic acid to the astragalus saponin is 2:2:3.
3. The glycosylated puerarin-containing composition according to claim 1, characterized in that: the preparation of the glycosylated puerarin adopts glycosylase to biologically transform puerarin.
4. The glycosylated puerarin-containing composition according to claim 1, characterized in that: the composition is in the form of tablet, capsule, granule, pill, oral liquid or injection.
5. The glycosylated puerarin-containing composition according to claim 1, characterized in that: the composition further comprises a pharmaceutically acceptable carrier.
6. A method of preparing the glycosylated puerarin-containing composition of claim 1, characterized in that: the method comprises the following steps:
s1, biologically converting puerarin into glycosylated puerarin by glycosylase;
s2, drying and crushing glycosylated puerarin at 50-60 ℃;
s3, mixing glycosylated puerarin, beta- (3, 4-dihydroxyphenyl) lactic acid and astragalus saponin according to the mass ratio of 1-2:2-4:3-5 to obtain the composition.
7. Use of a composition comprising glycosylated puerarin according to any of claims 1-5 for the preparation of a medicament for reducing TMAO content.
8. Use of a composition comprising glycosylated puerarin according to any of claims 1-5 for the preparation of a medicament for the treatment of vascular inflammation.
9. Use of a composition comprising glycosylated puerarin according to any of claims 1-5 for the preparation of a medicament for the treatment and/or prevention of atherosclerosis.
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| CN1562057A (en) * | 2004-03-31 | 2005-01-12 | 成都和康药业有限责任公司 | Medicinal composition for treating cardiocerobral diseases |
| CN101585858A (en) * | 2007-04-25 | 2009-11-25 | 南京师范大学 | Application of glycosylated puerarin derivate and its combination for preventing and treating cardiovascular and cerebrovascular disease |
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