CN105055402A - Composition of omega-3 series of poyenoic fatty acids and natural products - Google Patents
Composition of omega-3 series of poyenoic fatty acids and natural products Download PDFInfo
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Abstract
The invention relates to a composition of an omega-3 series of poyenoic fatty acids and natural products, for preventing and treating vasculopathy. The omega-3 series of poyenoic fatty acids refer to at least one of alpha-linolenic acid, gamma- linolenic acid, eicosapentaenoic acid and docosahexaenoic acid; the natural products refer to at least one of curcumin, silymarin, notoginsenoside and ginsenoside. The composition has great effect in preventing and treating macroangiopathy and microangiopathy caused by diabetes, hypertension, hyperlipidemia, tumor and other reasons unknown and is a new means and choice for prevention of vasculopathy.
Description
Technical field
The present invention relates to medical health field, particularly a kind of combination being used for vascular lesion control containing the serial polyenoic fatty acid of ω-3 and specific natural product.
Background technology
Along with the change of people's dietary structure and ambient environmental factors, the vascular lesion caused for reason with diabetes, hypertension, hyperlipidemia, tumor etc. is in the trend increased.Meanwhile, vascular lesion is also the common etiology basis of the multiple great chronic diseases such as cardiovascular and cerebrovascular disease, pulmonary hypertension, visceral organ injury.Current Chinese Patients with Cardiovascular/Cerebrovascular Diseases has 2.3 hundred million people, and the number dying from cardiovascular and cerebrovascular disease is every year 3,500,000, accounts for 41% of the various disease cause of the death, constitutes great threat to the health of the mankind.In sum, improve the prevention and therapy level of vascular lesion, become the significant medical and social problem of needing solution badly.
Alpha-linolenic acid is a kind of 18 carbon trivalent unsaturated fatty acids deriving from Semen Lini oil, Oleum Perillae, Fructrs Hippophae seed oil, fiery hemp seed oil, silkworm chrysalis oil, is a kind of ω-3 essential fatty acid.Its chemical structural formula is shown in shown in formula 1.
The chemical structural formula of formula 1 alpha-linolenic acid
Alpha-linolenic acid have blood fat reducing, cholesterol reducing, blood pressure lowering, anticancer, improve cardiovascular and cerebrovascular disease, improve the effect such as cranial nerve function, Polyglucan disease.
Gamma-Linolenic acid is a kind of unsaturated fatty acid deriving from seed of Radix Oenotherae erythrosepalae, and it and alpha-linolenic acid have similar structure, and both only have a position of double bond difference.Its chemical structural formula is shown in shown in formula 2.Gamma-Linolenic acid has the effects such as protection cardiovascular, blood fat reducing, blood sugar lowering.
The chemical structural formula of formula 2 gamma-Linolenic acid
The EPA that namely eicosapentaenoic acid it has often been said is useful to treatment coronary heart disease, hypertension and inflammation.Its chemical structural formula is shown in shown in formula 3.
The chemical structural formula of formula 3 eicosapentaenoic acid
The DHA that namely docosahexenoic acid it has often been said is the polybasic unsaturated fatty acid having six double bonds, is commonly called as " NAOHUANGJIN ", be nervous system cell growth and maintain important element, cerebral cortex and amphiblestroid content higher.Its chemical structural formula is shown in shown in formula 4.
The chemical structural formula of formula 4 docosahexenoic acid
Curcumin (Curcumin) is that one derives from zingiberaceous plant Radix Curcumae (CurcumaaromaticaSalisb.), Rhizoma Curcumae Longae (C.longaL.), Rhizoma Curcumae (C.zedoaria (Berg.) Rosc.), or a kind of plant polyphenol in aroid Rhizoma Acori Graminei (AcoruscalamusL.) rhizome.Its chemical structural formula is shown in shown in formula 5.
The chemical structural formula of formula 5 curcumin
Curcumin uses mainly as a kind of edible food colour and flavoring agent, is widely used in food-processing industry.Many-sided pharmacologically active such as research in recent years reports curcumin hepatoprotective, antiinflammatory, antibacterial, antitumor, prevent diabetes.
Silymarin (Silymarin) refers to the general name of the flavanolignan's compounds extracted from the seed coat of feverfew Herba Silybi mariani (also known as Herba Silybi mariani, mouse muscle, water flies Phasiana) seed.Its significant main component is Silybin A and B, Isosilybin A and B, silidianin and Silychristin, and their structural formula as shown in Equation 6.
Formula 6: the chemical structural formula of silymarin constituent
Silymarin uses mainly as a kind of natural product of hepatoprotective, long-term research confirms: the damage that silymarin can prevent ethanol, chemical toxicant, heavy metal, medicine, sitotoxin, environmental pollution etc. from causing liver, promote hepatocellular regeneration and reparation, be therefore called as " natural hepatoprotective ".In addition, silymarin also can be used as powerful antioxidant and uses, and plays the effect of the free radical removed in human body, slow down aging.
Arasaponin (PanaxNotoginsengSaponins) derives from panax araliaceae plant, is the general name of the saponins material that Radix Notoginseng contains, mainly comprises Panax Notoginseng saponin R
1, Panax Notoginseng saponin R
2, ginsenoside Rg
1, ginsenoside Rb
1, ginsenoside Re, ginsenoside Rg
3, ginsenoside Rh
1deng.Arasaponin has blood circulation promoting and blood stasis dispelling, it is active to promote blood circulation, anticoagulant and increase the effects such as heart and brain blood flow.
Ginsenoside (Ginsenoside) is a kind of gonane steroid core deriving from Araliaceae Radix Ginseng, mainly comprises ginsenoside Rg
1, ginsenoside Rg
2, ginsenoside Rb
1, ginsenoside Rb
2, ginsenoside Re, ginsenoside Rg
3, ginsenoside Rh
1, ginsenoside Rh
2, ginsenoside Rh
3deng.Life saponin has the effects such as prevention opposing tumor, resisting fatigue, enhancing human body immunity power.Arasaponin, ginsenoside's parent nucleus chemical structural formula are as shown in Equation 7.
The parent nucleus chemical structural formula of formula 7 arasaponin, ginsenoside.
Summary of the invention
The invention provides a kind of new composition of natural products, and the purposes in its trunk caused at prevention and therapy a variety of causes and microangiopathies.This at least one comprised primarily of the serial polyenoic fatty acid of ω-3 in alpha-linolenic acid, gamma-Linolenic acid, eicosapentaenoic acid and docosahexenoic acid, with the compositions of at least one in curcumin, silymarin, arasaponin, ginsenoside as natural product, can be used as medicine, functional food, health product, bread and cheese main component for the control of vascular lesion.
The invention provides and comprise alpha-linolenic acid by the serial polyenoic fatty acid of ω-3, gamma-Linolenic acid, at least one in eicosapentaenoic acid and docosahexenoic acid, with curcumin, silymarin, arasaponin, at least one in ginsenoside coordinates as the combination of natural product the method for prevention and therapy being used for vascular lesion, its coupling has been played the effect of Synergistic, for control by diabetes, hypertension, hyperlipidemia, the trunk that tumor and other unknown causes cause, there is obvious effect microangiopathies aspect, a kind of new means and selection is provided for preventing and treating above-mentioned vascular lesion.
The invention provides at least one comprised with the serial polyenoic fatty acid of ω-3 in alpha-linolenic acid, gamma-Linolenic acid, eicosapentaenoic acid and docosahexenoic acid, with the effective ingredient of at least one in curcumin, silymarin, arasaponin, ginsenoside as natural product.Particularly, fatty acid and natural product in compositions of the present invention, calculate with physical presence gauge, and its weight ratio should between 1:0.05-1:0.8, preferably between 1:0.05-1:0.5, and preferably 1:0.1.
The invention provides the compositions with the serial polyenoic fatty acid of ω-3 and natural product, comprise in alpha-linolenic acid, gamma-Linolenic acid, eicosapentaenoic acid, docosahexenoic acid, with in curcumin, silymarin, arasaponin, ginsenoside, the two above combination arbitrarily; Preferably be combined as in eicosapentaenoic acid, docosahexenoic acid and curcumin, silymarin, arasaponin, in ginsenoside, the two above combination arbitrarily; Preferably be combined as in alpha-linolenic acid, gamma-Linolenic acid and curcumin, silymarin, in arasaponin, the two above combination arbitrarily.
The serial polyenoic fatty acid of ω-3 of the present invention and natural products component can be commercially available prod, also can extract by plant material the content product or synthetic succedaneum that are prepared from routinely.
The serial polyenoic fatty acid of ω-3 of the present invention and composition of natural products, can use as the raw material of medicine, functional food, health product, common product, the trunk caused for prevention and therapy a variety of causes and microangiopathies.Take the present composition as the various dosage forms that principle active component is developed, include but not limited to tablet, capsule, oral liquid, syrup, granule, drop pill, oral cavity disintegration tablet, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion.
Detailed description of the invention
Further illustrate the present invention by the following examples, but not as limitation of the present invention.Set forth the beneficial effect inventing described compositions further by embodiment simultaneously, these experimental examples comprise present composition antiplatelet aggregation experiment in vitro, antiplatelet aggregation experiment in vivo, on experimental atherosclerosis rats hemorheology impact experiment, Effect study on the impact of vascular lesion nephropathy caused by diabetes.
Embodiment 1
Get the Semen Lini oil 10g that alpha-linolenic acid content is 70%, get the silymarin 0.75g that content is 95%, by both mix homogeneously, to obtain final product.
Embodiment 2
Get the seed of Radix Oenotherae erythrosepalae oil 10g that gamma-linolenic acid content is 70%, get the curcumin 0.75g that content is 95%, by both mix homogeneously, to obtain final product.
Embodiment 3
Get the Semen Lini oil 10g that alpha-linolenic acid content is 70%, get the curcumin 0.40g that content is 95%, get the silymarin 0.40g that content is 95%, by three's mix homogeneously, to obtain final product.
Embodiment 4
Get the fish oil 10g that DHA content is 50%, get the arasaponin 1.0g that content is 50%, by the two mix homogeneously, to obtain final product.
Embodiment 5
Get the fish oil 10g that EPA content is 80%, get the ginsenoside 1.0g that content is 80%, by the two mix homogeneously, to obtain final product.
Embodiment 6
Get the Semen Lini oil 10g that alpha-linolenic acid content is 80%, get content be 95% curcumin 0.25g, the content silymarin 0.20g that is 95%, the content arasaponin 0.25g that is 80%, content be 80% ginsengenin 20 .25g, by five mix homogeneously, to obtain final product.
Experimental example 1: antiplatelet aggregation experiment in vitro
The rabbit extracorporeal platelet aggregation effect of the anti-arachidonic acid-induction of fatty acid and composition of natural products is tested.The dosage intraperitoneal injection of anesthesia rabbit of the chloral hydrate 3mL/kg with 10%, blood is got from common carotid artery, be collected in disposable plastic tube, adopt 3.2% sodium citrate anticoagulant, when getting blood, in vitro the ratio of sodium citrate and amount for taking blood is 1: 9, put upside down mixing blood after getting immediately and obtain upper liquid and platelet rich plasma in room temperature with the centrifugal 10min of 1000r/min, after getting supernatant, remainder obtains platelet poor plasma with the centrifugal 10min of 3000r/min, Platelet mensuration is carried out by turbidimetry, record platelet aggregation rate, and ［ (control tube aggregation rate-sample cell aggregation rate)/control tube aggregation rate × 100% ］ calculates each test composition and represents with mean ± standard deviation (X ± S) the suppression ratio experimental result data of platelet aggregation with the formula, the results are shown in Table 1.
Table 1: each test composition is on the impact (X ± S) of the rabbit extracorporeal platelet aggregation of arachidonic acid-induction
Experimental result shows alpha-linolenic acid and all has inhibitory action to platelet aggregation in vitro by sample prepared by each embodiment method; Embodiment group is all better than alpha-linolenic acid group, conbined usage successful both proving; In embodiment group, each group difference is little, and embodiment 3 effect is slightly outstanding.
Experimental example 2: antiplatelet aggregation experiment in vivo
Get GK/Jcl type Ⅱdiabetes mellitus rat 60, be divided into medicine-feeding test group and model group at random and start administration.Test is divided into five groups, and administration group gastric infusion every day once.Blank group gives to distill 8ml/kg every day; Model control group gives distilled water 8ml/kg every day; Alpha-linolenic acid administration group gives 100mg/kg using content 95% alpha-linolenic acid as trial drug every day; Natural product administration group gives 100mg/kg using content 95% curcumin and silymarin (1:1) as trial drug every day; Compositions administration group gives 100mg/kg using the compositions in embodiment 3 as trial drug every day, altogether administration 2 weeks.1h after last administration, rats by intraperitoneal injection chloral hydrate 300mg/kg anaesthetize, abdomen venous blood collection, on platelet aggregation instrument, detect platelet aggregation, the results are shown in Table 2.
The each trial drug of table 2 is on the impact (X ± S) of rat platelet aggregation
Experimental result shows: model control group Platelet Aggregation rate obviously increases, and the compositions in alpha-linolenic acid group, natural product group and embodiment 3 groups obviously can reduce platelet aggregation rate, i.e. anticoagulant, best with embodiment 3 groups of effects.
Experimental example 3: the impact of experimental atherosclerosis rats hemorheology is tested
Select the basically identical male SD rat of body weight 60, be divided into matched group, medicine-feeding test group, model group at random.Configuration is containing 20% Adeps Sus domestica, 10% cholesterol, 2% sodium cholate, 1% methimazole, 20%(volume ratio) Tween 80,20%(volume ratio) the mixing-in fat Emulsion of propylene glycol.Blank group gives normal diet and distilled water 8ml/kg; Model control group gives high fat diet and distilled water 8ml/kg; Fatty acid group gives high fat diet and content 95% alpha-linolenic acid, and every day gives 100mg/kg; Natural product group gives high fat diet and natural product (content 95% curcumin and silymarin 1:1), and every day gives 100mg/kg; Compositions group gives the compositions in high fat diet and embodiment 3, and every day gives 100mg/kg.
Continuous experiment is after 13 days, animal fasting 12h, and urethane is anaesthetized, and carotid artery intubate is taken a blood sample, and measures Thrombus-index with platelet adhesion and thrombosis double-purpose instrument; Get sodium citrate anticoagulant, survey platelet adhesion rate; Taking heparin anticoagulant, measure erythrocyte sedimentation rate (ESR) and packed cell volume (HOT), rotary-tube type Blood rheology measurement measures whole blood viscosity (η L), blood reduced viscosity (RV) under whole blood viscosity (η H) under high shear rate, low shear rate.The results are shown in Table 3.
Table 3 couple experimental atherosclerosis rats ESR, HCT and whole blood viscosity (mPa.s
-1) impact (X ± S)
Experimental result shows, three groups of experimental grouies all obviously can reduce η H, η L, RV, ESR and HOT of experimental atherosclerosis rats, have pointed out the effect of prevention and therapy atherosclerosis and coronary heart disease; Wherein best with embodiment 3 groups of effects again.
Experimental example 4: on the impact experiment of rat aorta pathological changes nephropathy caused by diabetes
After rat adaptability raises 14 days, be divided into blank group (12) and modeling group at random.After water 12h is can't help in the fasting of modeling group, through abdominal cavity shot streptozotocin (STZ) 45mg/kg, survey fasting glucose with tail venous blood sampling after three days and be greater than 16.7mmol/L for modeling success, blank group injects isopyknic normal saline in contrast.48 diabetes rats that blood glucose is still not less than this level after one week are divided into medicine-feeding test group and model group at random and start administration.
Test is divided into five groups, and administration group gastric infusion every day once.Blank group gives distilled water 8ml/kg every day; Model control group gives distilled water 8ml/kg every day; Alpha-linolenic acid administration group gives 100mg/kg using content 95% alpha-linolenic acid as trial drug every day; Natural product administration group, with content 95% curcumin and silymarin 1:1, gives 100mg/kg as trial drug every day; Compositions administration group gives 100mg/kg using the compositions in embodiment 3 as trial drug every day, altogether administration 4 weeks.Before last administration, all rat metabolic cages of 24h collect urine, are stored in-18 DEG C of refrigerators, for measuring urine micro protein (UMA); 1h after last administration, rats by intraperitoneal injection chloral hydrate 300mg/kg anaesthetize, abdomen venous blood collection, separation of serum, detect blood glucose (Glu), blood urea nitrogen (BUN), creatinine (Cre) content.The results are shown in Table 4.
The each trial drug of table 4 is on the impact (X ± S) of adriamycin-induced nephropathy in Wistar rats vascular lesion model
Experimental result shows, modeling is after 4 weeks, and rat UMA is apparently higher than blank group, and Glu, BUN, Cre content also obviously raises simultaneously, illustrates that Renal vascular is subject to obvious damage.Rat UMA, Glu, BUN, Cre content can be made lower than model control group to separately fatty acid; Giving separately natural product also can make rat UMA, Glu, BUN, Cre content lower than model control group; Embodiment 3 groups can obviously reduce UMA content; Glu, BUN, Cre content is also starkly lower than model control group simultaneously; illustrate that compositions has certain protective effect to the infringement of nephropathy vascular lesion, and action effect is than application alpha-linolenic acid and natural product all have clear superiority separately.
Claims (9)
1. a compositions for the serial polyenoic fatty acid of ω-3 and natural product, is characterized in that: described compositions is made up of the serial polyenoic fatty acid of ω-3 and natural product; The described serial polyenoic fatty acid of ω-3 is at least one in alpha-linolenic acid, gamma-Linolenic acid, eicosapentaenoic acid and docosahexenoic acid; Described natural product is at least one in curcumin, silymarin, arasaponin, ginsenoside.
2. a compositions for the serial polyenoic fatty acid of ω-3 and natural product, is characterized in that: in described compositions, and calculate with physical presence gauge, the weight ratio of the serial polyenoic fatty acid of described ω-3 and natural product is between 1:0.05-1:0.8; The weight ratio of the serial polyenoic fatty acid of preferred described ω-3 and natural product is between 1:0.05-1:0.5; The weight ratio of the serial polyenoic fatty acid of preferred described ω-3 and natural product is 1:0.1.
3. the compositions of the serial polyenoic fatty acid of ω-3 and natural product, it is characterized in that: described compositions is in alpha-linolenic acid, gamma-Linolenic acid, eicosapentaenoic acid, docosahexenoic acid and curcumin, silymarin, arasaponin, in ginsenoside, the two above combination arbitrarily; Preferably be combined as in eicosapentaenoic acid, docosahexenoic acid and curcumin, silymarin, arasaponin, in ginsenoside, the two above combination arbitrarily; Preferably be combined as in alpha-linolenic acid, gamma-Linolenic acid and curcumin, silymarin, in arasaponin, the two above combination arbitrarily.
4. the compositions as described in any one of right 1-3, it is characterized in that: described alpha-linolenic acid (α-LinolenicAcid) and gamma-Linolenic acid (γ-LinolenicAcid) derive from Semen Lini oil, seed of Radix Oenotherae erythrosepalae oil, Oleum Perillae, Fructrs Hippophae seed oil, fiery hemp seed oil, Pupa bombycis wet goods, or synthetic succedaneum, described eicosapentaenoic acid (EicosapentaenoicAcid) and docosahexenoic acid (DocosahexaenoicAcid) derive from fish oil, Sargassum etc., or synthetic substitutes.
5. the compositions as described in any one of right 1-3, it is characterized in that: described curcumin (Curcumin) derives from zingiberaceous plant Radix Curcumae (CurcumaaromaticaSalisb.), Rhizoma Curcumae Longae (C.longaL.), Rhizoma Curcumae (C.zedoaria (Berg.) Rosc.), or aroid Rhizoma Acori Graminei (AcoruscalamusL.), or synthetic succedaneum, described silymarin (Silymarin) derives from Compositae Silybum plant Herba Silybi mariani (Silybummarianum (L.) Gaertn.), or synthetic succedaneum, containing Silybin A (SilybinA), Silybin B (SilybinB), Isosilybin A (IsosilybinA), Isosilybin B (IsosilybinB), Silychristin (Silychristin), at least one in these six kinds of compositions of silidianin (Silydianin), described arasaponin (PanaxNotoginsengSaponins) derives from panax araliaceae plant (Panaxnotoginseng), or synthetic succedaneum, described ginsenoside (Ginsenoside) derives from Araliaceae Radix Ginseng (Ginseng), or synthetic succedaneum.
6. the purposes of the compositions described in any one of claim 1-5, is characterized in that: described compositions is used for the trunk that causes of prevention and therapy a variety of causes and microangiopathies.
7. the purposes of the compositions described in any one of claim 1-5, is characterized in that: for the preparation of medicine, and described medicine is used for the trunk that causes of prevention and therapy a variety of causes and microangiopathies.
8. medicine, functional food, health product or a food, is characterized in that: comprise the compositions described in any one of claim 1-5.
9. the pharmaceutical composition for vascular lesion control, it is characterized in that: comprise the compositions described in any one of claim 1-5, its pharmaceutical dosage form includes but not limited to tablet, capsule, oral liquid, syrup, granule, drop pill, oral cavity disintegration tablet, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion.
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| WO2021143751A1 (en) * | 2020-01-14 | 2021-07-22 | 中国科学院上海药物研究所 | Injectable long-acting analgesic pharmaceutical composition, preparation method therefor, and application thereof |
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| CN105962359A (en) * | 2016-05-10 | 2016-09-28 | 中国农业科学院油料作物研究所 | Composition with function of assisting in improving memory |
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| CN109288056A (en) * | 2018-10-08 | 2019-02-01 | 徐晓飞 | A kind of composition and its application containing curcumin, omega-3 polyunsaturated fatty acids and phosphatide |
| WO2021143751A1 (en) * | 2020-01-14 | 2021-07-22 | 中国科学院上海药物研究所 | Injectable long-acting analgesic pharmaceutical composition, preparation method therefor, and application thereof |
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