CN101104649B - Potassium alginate and composition thereof - Google Patents
Potassium alginate and composition thereof Download PDFInfo
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- CN101104649B CN101104649B CN2006100471999A CN200610047199A CN101104649B CN 101104649 B CN101104649 B CN 101104649B CN 2006100471999 A CN2006100471999 A CN 2006100471999A CN 200610047199 A CN200610047199 A CN 200610047199A CN 101104649 B CN101104649 B CN 101104649B
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- potassium alginate
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000027032 Renal vascular disease Diseases 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
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- 208000005392 Spasm Diseases 0.000 description 1
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- 229960004324 betaxolol Drugs 0.000 description 1
- NWIUTZDMDHAVTP-UHFFFAOYSA-N betaxolol Chemical compound C1=CC(OCC(O)CNC(C)C)=CC=C1CCOCC1CC1 NWIUTZDMDHAVTP-UHFFFAOYSA-N 0.000 description 1
- 229960003588 bevantolol Drugs 0.000 description 1
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- 238000010241 blood sampling Methods 0.000 description 1
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- OGHNVEJMJSYVRP-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2 OGHNVEJMJSYVRP-UHFFFAOYSA-N 0.000 description 1
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- QERUYFVNIOLCHV-UHFFFAOYSA-N darodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC2=NON=C12 QERUYFVNIOLCHV-UHFFFAOYSA-N 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- WQVZLXWQESQGIF-WJKBNZMCSA-N dilevalol hydrochloride Chemical compound Cl.C([C@@H](C)NC[C@H](O)C=1C=C(C(O)=CC=1)C(N)=O)CC1=CC=CC=C1 WQVZLXWQESQGIF-WJKBNZMCSA-N 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 1
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- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 229960003745 esmolol Drugs 0.000 description 1
- AQNDDEOPVVGCPG-UHFFFAOYSA-N esmolol Chemical compound COC(=O)CCC1=CC=C(OCC(O)CNC(C)C)C=C1 AQNDDEOPVVGCPG-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
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- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000002005 ganglioplegic effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002474 hydralazine Drugs 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 229960001195 imidapril Drugs 0.000 description 1
- KLZWOWYOHUKJIG-BPUTZDHNSA-N imidapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(O)=O)=O)CC1=CC=CC=C1 KLZWOWYOHUKJIG-BPUTZDHNSA-N 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 229960004427 isradipine Drugs 0.000 description 1
- 229960001632 labetalol Drugs 0.000 description 1
- 229960004340 lacidipine Drugs 0.000 description 1
- GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000002171 loop diuretic Substances 0.000 description 1
- 229960003963 manidipine Drugs 0.000 description 1
- ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
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- 210000004165 myocardium Anatomy 0.000 description 1
- 229960004255 nadolol Drugs 0.000 description 1
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- VZWXXKDFACOXNT-UHFFFAOYSA-N niludipine Chemical compound CCCOCCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCOCCC)C1C1=CC=CC([N+]([O-])=O)=C1 VZWXXKDFACOXNT-UHFFFAOYSA-N 0.000 description 1
- 229950000109 niludipine Drugs 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 229960005425 nitrendipine Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- 230000002746 orthostatic effect Effects 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
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- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
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- 238000001223 reverse osmosis Methods 0.000 description 1
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- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
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- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229940083618 sodium nitroprusside Drugs 0.000 description 1
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- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
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- 229960005221 timolol maleate Drugs 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Disclosed is a potassium alginate and a combination of the potassium alginate, the technique of the potassium alginate is characterized in that average molecular weight is between 60,000-120,000, viscosity is between 5 to 21 centipoises. The potassium alginate with the above-mentioned characteristics has a higher qualified rate compared with the potassium alginate whose average molecular weight is between 60,000-160,000 and viscosity is between 22 to 30 centipoises in the tests of content of main components, hardness and disintegration, and weight differences. Moreover, the potassium alginate with the above-mentioned characteristics is superior to the potassium alginate in other molecular weight segments in the aspects of being used as drug excipient and of integral functions of treating hypertension and hyperlipidemia. In addition, the potassium alginate with the above-mentioned characteristics can be combined with any western medicine, Chinese medicine and health food, and can play the best role in anti-hypertension, lipid-lowering and drug excipient. The potassium alginate can be either used as the drug excipient or as a novel anti-hypertensive drug of digestive tract sodium excretion.
Description
[technical field] the present invention relates to a kind of potassium alginate and composition thereof with new technical characterictic.
[background technology] potassium alginate (Potassium Alginate) claims that again Potassium polyalginate, its rational formula are (C
6H
7O
6K) n.This compound has been public as foodstuff additive.
The contriver has applied for that November 2 2004 a key name is called the patent of invention of " potassium alginate of middle high molecular section and composition thereof ", having proposed the molecular weight section therein is 60,000-160,000, viscosity is the potassium alginate of 22-30 centipoise, and the potassium alginate of this molecular weight section not only can be done the drug excipient use but also step-down, effect for reducing fat are arranged.This class material is called functional drug excipient, and its effect at pharmaceutical field is very valuable.But the potassium alginate of this molecular weight section be not very remarkable aspect the curative effect of drug excipient and step-down, lipopenicillinase, and needing by experiment, research further improves.From then on, the contriver is actively seeking therapeutic action and the more significant molecular weight section of vehicle comprehensive function always.
[summary of the invention] the present invention has overcome the deficiency of above-mentioned prior art, and one of its purpose is to provide a kind of potassium alginate with new technical characterictic.
Two of purpose of the present invention is to provide the composition that possesses above-mentioned technical characterictic potassium alginate.
The potassium alginate of indication of the present invention is intended to and the unique curative effect of compatibility of drugs combination performance with step-down, effect for reducing fat, and itself again can be as drug excipient, for the practical application of these medicinal composition provides theoretical foundation.
Above-mentioned purpose of the present invention is achieved through the following technical solutions.
A kind of potassium alginate, its technical characterictic is molecular-weight average 60,000-120, between 000, viscosity is the 5-21 centipoise.
The contriver has proposed a kind of potassium alginate with following technical characterictic through studying for a long time and test of many times:
1, be reference substance with Dextran T polysaccharide, 0.1molNacl is that the elutriant of the mean molecule flow measurement of elutriant is measured on the curve, and the pairing molecular weight in the climax of optical density A is 60,000-120, between 000, promptly its molecular-weight average is 60,000-120,000.
2, use rotary viscosity design determining, its viscosity is the 5-21 centipoise.
Above-mentioned technical characterictic 1 can also be used the reverse osmosis technical measurement except that measuring with Dextran reference substance elutriant assay method.
The potassium alginate that possesses above-mentioned technical characterictic is 60 than molecular weight aspect drug content inspection, weight differential, hardness test, disintegration inspection, 000-160,000, viscosity is that the qualification rate of potassium alginate of 22-30 centipoise is higher.
The potassium alginate that possesses above-mentioned technical characterictic can make up with any Western medicine, Chinese medicine and protective foods, and this medicinal composition all can be brought into play best effect aspect the figuration of step-down, lipopenicillinase and medicine.In above-mentioned all kinds of medicinal composition, potassium alginate both can be a drug excipient, also can be the new class antihypertensive drugs of " digestive tube row sodium class ".
Possess the medicinal composition that the potassium alginate of above-mentioned technical characterictic participates in, its step-down, effect for reducing fat are 60 than molecular weight, 000-160,000, viscosity is that the medicinal composition effect that participates in of the potassium alginate of 22-30 centipoise is more obvious.
One class contains the medicinal composition of above-mentioned potassium alginate component, it is characterized in that containing the depressor component in the said medicinal composition, and this depressor can be divided into the beta-blocker component by its classification; Or/and calcium antagonist component; Or/and angiotensin converting enzyme inhibitor component; Or/and vasodilator component; Or/and diuretic(s) component; Or/and one or more arbitrary combination of maincenter depressor component, the weight of above-mentioned depressor component is the 0.001-100% of potassium alginate composition weight, in above-mentioned each medicinal composition, potassium alginate can be a drug excipient, also can be the new class antihypertensive drugs of " digestive tube row sodium class ".
One class contains the medicinal composition or the protective foods of above-mentioned potassium alginate component; it is characterized in that containing in said medicinal composition or the protective foods Chinese medicine depressor; this depressor be earthworm, Huang Qin, Slender Dutchmanspipe Root, before bone, the car, one or more arbitrary combination of trailing plants cloth fiber crops leaf, blue or green tangerine, Motherwort Herb, cow-bezoar, pearl, chrysanthemum component, the weight of above-mentioned depressor component is the 1-200% of potassium alginate composition weight.
One class contains the medicinal composition or the protective foods of above-mentioned potassium alginate component, it is characterized in that containing in said medicinal composition or the protective foods lipid lowerers component, this lipid lowerers is a Colestyramine, colestipol, lovastatin, Pravastatin, probucol, nicotinic acid, Inositol Hexanicotinate, ASIMO this, the chloroethene spy, bezafibrate, ML-1024, non-unconcerned Bei Te, gemfibrozil, Pantethine or natural lipopenicillinase activeconstituents polyenoic acid Yelkin TTS, one or more arbitrary combination of Ginkgo biloba extract component, the weight of above-mentioned lipid lowerers or natural lipopenicillinase active ingredient components is the 0.001-100% of potassium alginate composition weight.
Describe with test below:
Test one: do auxiliary material respectively with the potassium alginate that possesses above-mentioned two kinds of technical characterictics, make nifedipine sheet I and nifedipine sheet II, to observe its qualification rate, every result following (with 100,000 statistics):
The every inspection item of table 1 nifedipine sheet I and nifedipine sheet II relatively
| Group | Visual inspection | Drug content is checked | Weight differential | Hardness test | Disintegration is checked |
| Nifedipine sheet I | 99.2％ | 99.8％ | 100％ | 99.8％ | 99.7％ |
| Nifedipine sheet II | 99.8％ | 100％ | 100％ | 100％ | 99.9％ |
In the table 1, nifedipine I sheet is 60 with molecular weight, 000-160,000, viscosity is that the potassium alginate of 22-30 centipoise is a vehicle; Nifedipine II sheet is 60 with molecular-weight average, 000-120,000, viscosity is that the potassium alginate of 5-21 centipoise is a vehicle.Analyze every result, nifedipine II sheet is than the qualification rate height of nifedipine I sheet, and this explanation nifedipine II sheet is in the dilution of vehicle, disintegration, aspect better effects if such as bonding.
Test two: see the antihypertensive effect comparison of nifedipine sheet I and nifedipine sheet II of the potassium alginate combination of above two kinds of different technologies features again, the result is as shown in the table:
Table 2 nifedipine sheet I and nifedipine sheet II antihypertensive effect are relatively
| Group | Basic mean blood pressure before the treatment | Took medicine back 24 hours | Take medicine 2 weeks of back | Take medicine 4 weeks of back | After the drug withdrawal 2 days | After the drug withdrawal 4 days | After the drug withdrawal 6 days |
| Nifedipine sheet I | 187/101 | 161/95 | 143/87 | 140/85 | 145/88 | 152/96 | 167/99 |
| Nifedipine sheet II | 186/102 | 158/93 | 151/85 | 136/83 | 142/86 | 150/90 | 163/95 |
As can be seen from Table 2, nifedipine II sheet is to the reduction amplitude of relax swelling pressure and systolic pressure, greater than nifedipine I sheet.In I sheet and II sheet, the medication of nifedipine and potassium alginate is than identical, and it is identical that day is taken the sheet number, every group of several 20 people of the experimenter, and it is right to divide at random, and day dose nitre benzene ground is 40mg, and potassium alginate is 4g.
Test three: see the potassium alginate that possesses above-mentioned two kinds of different technologies features and Max EPA composition effect for reducing fat again to hyperlipemia in mice.It is 60 that composition I adopts molecular weight, 000-160,000, viscosity is the potassium alginate of 22-30 centipoise; It is 60 that composition I I adopts molecular-weight average, 000-120,000, viscosity is the potassium alginate of 5-21 centipoise.Two groups of composition component content are potassium alginate 1.5g/Kg, Max EPA 0.75g/Kg.Get 40 of healthy mices, female, hero half and half, 20 every group, the test number of days is 7 days.The last administration in the mouse tail blood sampling, was measured serum cholesterol, triglyceride and high-density lipoprotein (HDL) with semi-automatic determinator after 24 hours, the results are shown in following table:
Table 3 potassium alginate and Max EPA composition are to the effect x ± SD n=20 of hyperlipemia in mice
| Group | Dosage g/Kg | Serum cholesterol mMol/L | Triglyceride mMol/L | High-density lipoprotein (HDL) mMol/L |
| Composition I | Sea more than 1.5 0.75 | 5.192±1.679 | 0.363±0.139 | 1.120±0.208 |
| Composition I I | Sea more than 1.5 0.75 | 4.925±1.010 * | 0.292±0.115 * | 1.252±0.215 * |
Annotate: in the table 3, sea more than 1.5 0.75 expression potassium alginates and the content of Max EPA in composition are respectively 1.5g/Kg and 0.75g/Kg.
Compare with composition I,
*P＜0.05
As seen from above-mentioned, molecular-weight average is 60,000-120,000, viscosity be the potassium alginate of 5-21 centipoise aspect the effect of vehicle, the curative effect aspect of decompression, lipopenicillinase, all being better than molecular-weight average is 60,000-160,000, viscosity is the potassium alginate of 22-30 centipoise.
[embodiment] in following example, all adopting molecular-weight average is 60,000-120, and 000, viscosity is the potassium alginate of 5-21 centipoise.
Embodiment one: make medicinal composition with depressor and potassium alginate, the depressor composition weight that contains in this medicinal composition is the 0.005%-60% of potassium alginate composition weight.Above-mentioned depressor can adopt beta-blocker, but as the commonly used clinical depressor hydrochloric acid Pu Nailuoer of present use, timolol maleate, for comet Luo Er, nadolol, sotalol, Bopindolol, bucumolol, A Leiluoer, 7-[2-hydroxy-3-(isopropylamino)propoxy, fluorine Luo Er, bevantolol, venue of sports event Luo Er,, bisoprolol, Tartaric acid metoprolol, alprenolol, betaxolol, esmolol, acebutolol, amosulalol, Trate, Sch-19927, Arottnolol, Kredex, Celiprolol.
Beta-blocker is the hypertensive choice drug of treatment, wherein but metoprolol tartrate is β-Le common drug, with potassium alginate combination conduct experiment medicine, β-Le can distinguish medicine in contrast with potassium alginate, select primary hypertension patient 60 people age-based, sex, the state of an illness, be divided into three groups after the pairings such as body weight at random, every group 20 people, taking β-Le for one group can, day dose 100mg takes potassium alginate for second group, day dose 8g, the 3rd group take β-Le can with the potassium alginate composition, but day dose β-Le 60mg, potassium alginate 4g takes two week back result such as following tables.
Table 4n=20
| Group | Effectively | Produce effects | Add up to | Total effective rate | Statistics |
| β-Le can organize | 7 | 6 | 13 | 65％ | |
| The potassium alginate group | 8 | 9 | 17 | 85％ | |
| The composition group | 9 | 10 | 19 | 95％ * | P<0.05 |
*Adopt the method check of card side
To the experiment be summarized as follows:
1, the curative effect of checking composition with card side method apparently higher than control group β-Le can and potassium alginate P＜0.05.
2, but the β in the composition-Le component and potassium alginate component day dose can be organized and the potassium alginate group obviously reduces than control group β-Le.
3, β-Le can organize anxious, the unusual sense of four-player appearance, cardio palmus shape, and composition group no one has untoward reaction.
4, the composition group persistent advantage of onset curative effect fast and the potassium alginate group of having concentrated β-Le to organize, 3 days blood pressures are kept treatment level after the drug withdrawal, slowly go up in 4-6 days.
The step-down mechanism of beta-blocker is optionally to combine with beta-receptor in the adrenoceptor, hinder the noradrenergic nerve mediator to combine with beta-receptor, produce adrenolytic, cardiac insufficiency, asthma, peripheral blood vessel spasm, hypoglycemia, bradyrhythmia, the careful usefulness of atrioventricular block person.Base side effect and untoward reaction be usually as seen: anxious, neurotic, maincenter dysthymia disorders, dreaminess, illusion, vomiting, headache, palpitaition, tachycardia, weak, tremble, perspiration, apocleisis, feel sick, stomachache, serious hypertension.
Make medicinal composition with above-mentioned any one or more than one beta-blocker and potassium alginate, the beta-blocker depressor composition weight that contains in this medicinal composition is the 0.001-10% of potassium alginate composition weight, can obviously reduce the side effect of beta-blocker depressor.
Table 5 composite formula
| Prescription | Every | Per ten thousand |
| Metoprolol tartrate | 8mg | 80g |
| Potassium alginate | 0.5g | 5Kg |
| Other auxiliary material | In right amount | In right amount |
Antihypertensive drug, ampoule 2-6 sheet, day clothes secondary.
Embodiment two: clinical normal selection diuretic(s) and beta-blocker share, to alleviate the hypokalemia that some diuretic(s) is caused, be used as hydrochlorothiazide and beta-blocker, as adding potassium alginate again, can obtain special-effect clinically, not cause orthostatic ypotension and electrolyte disturbance, the fair weighing apparatus of the follow-up continuation of insurance of drug withdrawal blood pressure 4-6 days, obviously alleviate epigastric discomfort, burnout and parahypnosis etc.
Embodiment three: calcium antagonist is the very potential depressor of a class, and calcium antagonist commonly used at present has nifedipine, nicardipine, nitrendipine, nimodipine, amlodipine, niludipine, Isrodipine, Buddhist nun's comet Horizon, Felodipine, Darodipine, SKF-102362, Manidipine, Lacidipine (62, benidipine, barnidipine etc.
The step-down mechanism of above-mentioned calcium antagonist is to suppress calcium ion to stride in the film stream and influence calcium ion and act in cell, and the medicine that whole cell function is changed, since it make vessel wall and myocardial cell starch in the free calcium ion concn descend, myocardial contraction weakens and is the negativity muscular strength and uses, reduce cardiac muscle power consumption oxygen consumption, expansion surrounding blood vessel, blood pressure reduce, and cardiac load alleviates.
Take the common side effect of calcium antagonist headache, dizziness, flush, ypotension, numb limbs and tense tendons, nausea and vomiting, weak etc. are arranged.
Before addressed the effect that potassium alginate and nifedipine compatibility use.
Table 6 composite formula
| Prescription | Every | Per ten thousand |
| Nifedipine (nifedipine) | 10mg | 5g |
| Potassium alginate | 0.5g | 5Kg |
| Other auxiliary material | In right amount | In right amount |
Antihypertensive drug, each 2-4 sheet, every day secondary.
Embodiment four: potassium alginate and angiotensin converting enzyme inhibitor combination.
Angiotensin converting enzyme inhibitor is the emerging rising depressor of a class, commonly used captopril, enalapril, Ah piece Puli, thunder end Puli, quinapril, delapril hydrochloride, Yipingshu, benazepril, Tanatril is arranged, accompanies diindyl Puli etc.
Step-down mechanism: feritin is a kind of proteolytic ferment, after being secreted into blood, the feritin substrate of one one kinds of alpha-globulins of proangiotensin that liver is produced is cracked into the angiotensin I of decapeptide after conversion enzyme (kininase) effect, generate Angiotensin II and III, Angiotensin II can promote the synthetic release of aldosterone, angiotensin converting enzyme inhibitor ACEI suppresses the generation of Ang II (being Angiotensin II), thereby suppressing kininase brings high blood pressure down, by the hypertension due to the renal vascular disease, ACEI is responded, general essential hypertension 60%-70% has the step-down reaction, this hypotensor is less than the depressor side effect of other classifications, and common having choked and coughed, fash, heating etc.Angiotensin converting enzyme inhibitor is many to be share with diuretic(s), and effect is strengthened, and reduces the hypokalemia due to the latter, and diuretic(s) can reduce Q volume of blood, increase Na
+Drain, the two is used total effective rate can reach 80-85%.Make medicinal composition with above-mentioned any one or more than one angiotensin converting enzyme inhibitor and potassium alginate, this medicinal composition can make up with the foregoing description, forms new compound chinese-western medicine preparation.
Potassium alginate and angiotensin converting enzyme inhibitor captopril (captopril) combination:
Clinical trial: select primary hypertension patient 48 people, after age-based, sex and the state of an illness pairing, be divided into three groups at random, every group 16 people takes captopril (formal name used at school captopril) 20mg sheet, three of every days for one group; Another group is taken potassium alginate, every day secondary, day clothes 8g; Take potassium alginate captopril composition group for the 3rd group, 6 of day clothes compound captopril 5mg sheets, wherein potassium alginate 3g.Experimental result is as follows:
Table 7
| Group | Basic mean blood pressure before taking | Mean blood pressure after three weeks of treatment | Efficient | Obvious effective rate | Total effective rate |
| The captopril group | 178/103 | 156/95 | 25％ | 38％ | 63％ |
| The potassium alginate group | 175/101 | 138/89 | 35％ | 46％ | 81％ |
| The composition group | 181/104 | 136/84 | 39％ | 56％ | 95％ * |
*Annotate P＜0.01: the mmHg of blood pressure unit is efficient, obvious effective rate is evaluated standard rating with depressor.
Side effect is compared: captopril group three people occur choking and cough pharyngeal dryness; Three people fash occurs and follow low-heat, and second day blood pressure rises to former level after the common drug withdrawal.
The potassium alginate group does not have uncomfortable phenomenon, but onset is slow, and the back beginning step-down in the 3rd day of taking medicine was started and to be waved ideal effect on the the 5th to six day, and patient's sleeping state improving has convenient logical intestines effect simultaneously.
Above-mentioned symptom appears in composition group no one, and onset is fast, keeps treatment level in three days after the drug withdrawal, bottom out in the 4th day, and the approaching former level to the 6th day, patient's sleeping state improving, logical intestines are convenient.
The prescription of above-mentioned composition is as follows:
Table 8 composite formula
| Prescription | Every | Per ten thousand |
| Captopril (captopril) | 5mg | 50g |
| Potassium alginate | 0.5g | 5Kg |
| Other auxiliary material | In right amount | In right amount |
| Antihypertensive drug | Once take the 3-4 sheet | Day is obeyed secondary |
Revision test, scale-up, all must with above-mentioned test equifinality.
Embodiment five: potassium alginate and vasodilator combination.
A lot of classes are arranged in the vasodilator, because energy vasodilation, recycle system Peripheral resistance is weakened, cardiac load alleviates, blood pressure drops, the medicament categories that can distend the blood vessels is also a lot, comprises calcium antagonist and angiotensin converting enzyme inhibitor that the front was said, still has 1 in addition) directly act on the vascular smooth muscle cartridge bag and draw together the hydralazine of expansion artery pipe, the Yin handkerchief peace of rattling away; The Sodium Nitroprusside of expansion artery and vein; 2) alpha-receptor blocade; 3) ganglioplegic; 4) blocade such as serpentine behind the intersection neuroganglion; 5) other.
Each classification of the common adverse effect of this type of medicine is had nothing in common with each other again, with retarding agent serpentine behind the intersection neuroganglion, the amplitude that this type of drug effect is slow, blood pressure reduces is also undesirable, but this type of antihypertensive drugs is safe and reliable, serpentine is used for compound blood pressure reducing and has more than ten years, so far be hyperpietic's medicine commonly used, dry, nasal obstruction phenomenon can appear in user once in a while.
Compound Reserpine is equipped with hydragog(ue) based on serpentine, and anti-allergic drug and multivitamin are formed, if serpentine and potassium alginate are made medicinal composition, this medicinal composition can make up with the foregoing description, forms the compound chinese-western medicine preparation.The characteristics of this compound chinese-western medicine preparation are: rapid depressurization, do not rebound, and untoward reaction and side effect are little.
Table 9 composite formula
| Prescription | Every | Per ten thousand |
| Serpentine | 0.13mg | 1.3g |
| Blue starch | 0.005g | 50g |
| Potassium alginate | 0.5g | 5Kg |
| Other auxiliary material | In right amount | In right amount |
Antihypertensive drug is once taken the 4-6 sheet, every day secondary.
Embodiment six: potassium alginate and diuretic(s) combination.
Diuretic(s) generally is not listed in the depressor scope in classification, take but middle effect hydragog(ue) thiazides is commonly used for depressor, and the antihypertensive drugs compatibility of normal and other class uses.
Mention above, mainly at digestive tube row sodium, diuretic(s) then is to act on ascending thick limb of Henle's loop to potassium alginate, influences Na
+, Cl
-Active transport, thereby be loop diuretic again.
Potassium alginate and diuretic(s) drug combination, can improve the hypokalemia that causes by diuretic(s), from medullary loop and the two-way row's sodium of digestive tube, can strengthen antihypertensive effect, make medicinal composition with above-mentioned diuretic(s) and potassium alginate, contain the 0.001%-50% that the hydragog(ue) composition weight is the potassium alginate composition weight in this medicinal composition.
Table 10 composite formula
| Prescription | Every | Per ten thousand |
| Hydrochlorothiazide | 5mg | 50g |
| Potassium alginate | 0.5g | 5Kg |
| Other auxiliary material | In right amount | In right amount |
6-8 sheet of antihypertensive drug, every day secondary.
Embodiment seven: potassium alginate and the combination of other depressor.
The depressor of other type such as maincenter depressor, can make up with potassium alginate, containing cental system depressor composition weight in this medicinal composition is the 0.002-80% of potassium alginate composition weight, and present embodiment can make up with the foregoing description, forms new compound chinese-western medicine preparation.
Embodiment eight: potassium alginate and the Chinese traditional medicine composition that hypotensive effect is arranged.
Because the vehicle of chemical medicine can be used for Chinese medicine preparation, so potassium alginate can participate in the combination of Chinese medicine.
Some Chinese medicine has hypotensive effect, as earthworm, Huang Qin, Slender Dutchmanspipe Root, before bone, the car, trailing plants cloth fiber crops leaf, blue or green tangerine, Motherwort Herb, cow-bezoar, pearl, chrysanthemum etc.One or more of above Chinese medicine all can with the potassium alginate compatibility, form new Chinese traditional compound medicine.The Chinese medicine depressor composition weight that contains in this medicinal composition is the 30-150% of potassium alginate composition weight.Present embodiment can make up with the foregoing description, forms new compound chinese-western medicine preparation.
Be that potassium alginate and true chrysanthemum chiang ya wan are used in combination and use separately the result of true chrysanthemum chiang ya wan or potassium alginate to compare below.
Select the mild or moderate hyperpietic of 30 blood pressures between 160/100-142/91, after age-based, the sex state of an illness is matched, be divided into three groups at random, every group 10 people takes true chrysanthemum chiang ya wan for one group; Take potassium alginate for second group, restrain every days 6; Take potassium alginate and the combination of true chrysanthemum chiang ya wan for the 3rd group, potassium alginate gram every days 3, true chrysanthemum chiang ya wan ball every day 1, statistics is as follows:
Table 11n=10
| Group | Blood pressure before the treatment | Obey back 24 hours effective numbers | The effective number in one week back | The effective number in two week backs | Drug withdrawal is effective number after three days |
| Precious chrysanthemum chiang ya wan group | 155/97 | ?0 | ?5 | ?6 | ?2 |
| The potassium alginate group | 157/98 | 0 | 7 | 8 | 6 |
| The composition group | 156/98 | 2 | 9 | 9 | 8 |
From last table as seen, potassium alginate and the Chinese traditional medicine composition that hypotensive effect is arranged can obtain unexpected effect too, it is described and has the Chinese traditional medicine composition of hypotensive effect also can play synergy.Thereby potassium alginate can be made Chinese medicine preparations such as pill, powder, extract and pellet with Chinese prescription.
Embodiment nine: molecular-weight average is 60,000-120, between 000, viscosity is that the potassium alginate of 5-21 centipoise can make up with lipid lowerers, potassium alginate itself has step-down, effect for reducing fat, therefore its composition has the dual function of step-down, lipopenicillinase, and its effect for reducing fat is significantly improved than independent use fat-reducing medicament effect.
Step-down mechanism by rat test checking potassium alginate " digestive tube row sodium ".Get the healthy rat of body weight 150-180 gram, male and female half and half are divided equally 5 groups, 12 every group, give potassium alginate 200,600,1000mg/Kg that 2% sodium chloride solution is prepared respectively, respectively as potassium alginate low dose group, middle dosage group, high dose group.Model control group is given 2% sodium chloride solution, and the normal control group is given the ordinary water with volume, and single cage is raised, and collects ight soil after administration in the 1st day.Get every mouse 1-5 days, 6-10 days ight soil respectively at 40 ℃ of bakings in the baking oven 12 hours, weighing grinds that to take by weighing the 0.2g concentrated nitric acid nitrated, and 1500 rev/mins centrifugal 10 minutes, get supernatant liquor, atomic absorption spectrophotometry is surveyed sodium ions content, calculates row's sodium amount of 1-5 days, 6-10 day every group, result such as following table.
Table 12 potassium alginate is to rat ight soil row sodium amount influence (1-5 days) n=12
| Group | Dosage mg/Kg | 1-5 days row's sodium total amount mg |
| The potassium alginate low dose group | 300 | 201±59.6 |
| Dosage group in the potassium alginate | 600 | 216±60.0 * |
| The potassium alginate high dose group | 1000 | 225±105.4 * |
| Model control group | / | 195±24.5 |
| The normal control group | / | 180.5±76.0 |
With the model group ratio
*P＜0.05
Table 13 potassium alginate is to rat ight soil row sodium amount influence (6-10 days) n=12
| Group | Dosage mg/Kg | 6-10 days row's sodium total amount mg |
| The potassium alginate low dose group | 300 | 225.6±105.9 * |
| Dosage group in the potassium alginate | 600 | 230.7±113.5 ** |
| The potassium alginate high dose group | 1000 | 250.8±134.7 ** |
| Model control group | / | 193±24.5 |
| The normal control group | / | 175.5±75.6 |
With the model group ratio
*P＜0.05
*P＜0.001
Above-mentioned test-results has disclosed the step-down mechanism of potassium alginate " digestive tube row sodium ", is different from present existing antihypertensive drug fully, belongs to the antihypertensive drug of " digestive tube row sodium " class new class.
Is the composition group higher than the potassium alginate group to the reduction effect of blood pressure so?
Select 36 of SHR rats, measure blood pressure with the indirect manometry of CRS-3 type rat heart rate blood pressure determination instrument caudal artery, 37 ℃ of insulations of rat are 10 minutes before each the mensuration, according to the blood pressure of measuring before the administration, random packet, be divided into three groups, 12 every group, irritate stomach respectively and give potassium alginate 1.0g/Kg, potassium alginate 0.75g/Kg and Max EPA 0.5g/Kg, model control group gives the distilled water with volume, every day 1 time, continuous 7 days, measure blood pressure and heart rate next day of reaching first after the administration, survey altogether 4 times, check between the percentage that reduces with blood pressure is organized respectively, result such as following table:
Table 14 potassium alginate Max EPA composition is to the influence of blood pressure
N=12
With the model control group ratio
*P＜0.05
*P＜0.001
From statistic data as can be seen, the amount ratio folk prescription potassium alginate of potassium alginate in composition is little, but the percentage of step-down is better than the folk prescription potassium alginate.
Conclusion: potassium alginate and lipid lowerers compatibility, can obtain the combination formula of not only lipopenicillinase but also step-down, lipopenicillinase, antihypertensive effect are better than folk prescription lipopenicillinase and depressor, and consumption reduces, and illustrate to have positive synergy between the prescription.The at present natural lipopenicillinase of particularly marine natural, step-down medicinal composition are few, and therefore special effect is arranged.
Lipid lowerers commonly used such as Colestyramine, colestipol, lovastatin, Pravastatin, probucol, nicotinic acid, Inositol Hexanicotinate, ASIMO this, chloroethene spy, bezafibrate, ML-1024, non-unconcerned Bei Te, gemfibrozil, Pantethine component one or more can make up with potassium alginate.The lipid lowerers composition weight that contains in the aforesaid combination medicine is the 0.005-99% of potassium alginate composition weight.
Embodiment ten: potassium alginate and the active skull cap components combination with effect for reducing fat, any one or more than one combination as polyenoic acid, Yelkin TTS, Ginkgo biloba extract component, contain natural lipopenicillinase activeconstituents in the said composition, weight is the 10-70% of potassium alginate composition weight.
Because the plastic property of chemical medicine can be used in the protective foods, so potassium alginate can be combined into a variety of protective foodss with Chinese medicine with step-down, effect for reducing fat or active skull cap components.
What more than exemplify is preferred embodiment of the present invention, and all unsubstantialities of doing according to technical solution of the present invention improve, and when the function that is produced does not exceed the scope of technical solution of the present invention, all belong to protection scope of the present invention.
Claims (5)
1. potassium alginate, its technical characterictic is:
1) be reference substance with Dextran T polysaccharide, 0.1molNacl is that the elutriant of the mean molecule flow measurement of elutriant is measured on the curve, and the pairing molecular weight in the climax of optical density A is 60,000-120, between 000, promptly its molecular-weight average is 60,000-120,000;
2) use rotary viscosity design determining, its viscosity is the 5-21 centipoise.
2. a medicinal composition that contains the described potassium alginate of claim 1 is characterized in that containing in the said medicinal composition depressor component, and this depressor is the beta-blocker component; Or/and calcium antagonist component; Or/and angiotensin converting enzyme inhibitor component; Or/and vasodilator component; Or/and diuretic(s) component; Or/and one or more arbitrary combination of maincenter depressor component, the weight of above-mentioned depressor component is the 0.001-100% of potassium alginate composition weight, in above-mentioned each medicinal composition, potassium alginate is a drug excipient, also is the new class antihypertensive drugs of " digestive tube row sodium class " simultaneously.
3. medicinal composition according to claim 2; it is characterized in that containing in the said medicinal composition Chinese medicine depressor; this depressor be earthworm, Huang Qin, Slender Dutchmanspipe Root, before bone, the car, one or more arbitrary combination of trailing plants cloth fiber crops leaf, blue or green tangerine, Motherwort Herb, cow-bezoar, pearl, chrysanthemum component, above-mentioned depressor composition weight is the 1-200% of potassium alginate composition weight.
4. medicinal composition according to claim 2, it is characterized in that containing in the said medicinal composition lipid lowerers component, this lipid lowerers is a Colestyramine, colestipol, lovastatin, Pravastatin, probucol, nicotinic acid, Inositol Hexanicotinate, ASIMO this, the chloroethene spy, bezafibrate, ML-1024, non-unconcerned Bei Te, gemfibrozil, Pantethine or natural lipopenicillinase activeconstituents polyenoic acid Yelkin TTS, one or more arbitrary combination of Ginkgo biloba extract component, above-mentioned lipid lowerers or natural lipopenicillinase active ingredient components weight are the 0.001-100% of potassium alginate composition weight.
5. medicinal composition according to claim 3, it is characterized in that containing in the said medicinal composition lipid lowerers component, this lipid lowerers is a Colestyramine, colestipol, lovastatin, Pravastatin, probucol, nicotinic acid, Inositol Hexanicotinate, ASIMO this, the chloroethene spy, bezafibrate, ML-1024, non-unconcerned Bei Te, gemfibrozil, Pantethine or natural lipopenicillinase activeconstituents polyenoic acid Yelkin TTS, one or more arbitrary combination of Ginkgo biloba extract component, above-mentioned lipid lowerers or natural lipopenicillinase active ingredient components weight are the 0.001-100% of potassium alginate composition weight.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1156150A (en) * | 1996-12-18 | 1997-08-06 | 谭攸恒 | Process for preparing potassium alginate and its use |
| WO2001040315A1 (en) * | 1999-11-30 | 2001-06-07 | Dalian Yaweite Biology Engineering Co., Ltd. | The alginate having low molecular weight, methods of manufacturing it and its use |
| CN1461656A (en) * | 2002-05-28 | 2003-12-17 | 谭攸恒 | Medicinal excipient-potassium alginate and its composition |
| JP2004075635A (en) * | 2002-08-21 | 2004-03-11 | Maruzen Pharmaceut Co Ltd | Moisturizing agent and external preparation for skin |
| CN1769303A (en) * | 2004-11-02 | 2006-05-10 | 谭攸恒 | Middle,high molecular weight potassium alginate and its compositions |
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| CN1156150A (en) * | 1996-12-18 | 1997-08-06 | 谭攸恒 | Process for preparing potassium alginate and its use |
| WO2001040315A1 (en) * | 1999-11-30 | 2001-06-07 | Dalian Yaweite Biology Engineering Co., Ltd. | The alginate having low molecular weight, methods of manufacturing it and its use |
| CN1461656A (en) * | 2002-05-28 | 2003-12-17 | 谭攸恒 | Medicinal excipient-potassium alginate and its composition |
| JP2004075635A (en) * | 2002-08-21 | 2004-03-11 | Maruzen Pharmaceut Co Ltd | Moisturizing agent and external preparation for skin |
| CN1769303A (en) * | 2004-11-02 | 2006-05-10 | 谭攸恒 | Middle,high molecular weight potassium alginate and its compositions |
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