CN1461656A - Medicinal excipient-potassium alginate and its composition - Google Patents

Medicinal excipient-potassium alginate and its composition Download PDF

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CN1461656A
CN1461656A CN02109875A CN02109875A CN1461656A CN 1461656 A CN1461656 A CN 1461656A CN 02109875 A CN02109875 A CN 02109875A CN 02109875 A CN02109875 A CN 02109875A CN 1461656 A CN1461656 A CN 1461656A
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谭攸恒
陈玉琦
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/734Alginic acid
    • AHUMAN NECESSITIES
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P9/00Drugs for disorders of the cardiovascular system
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Abstract

A medicinal excipient, potassium alginate, is disclosed, which can also be used as the additive, emulsifier, suspending agent, or thickening agent of medicine. A composite medicine for reducing pressure and fat of blood is prepared from potassium alginate instead of sodium alginate and other Chinese medicines and/or Western medicines. Its advantages are quickly and durably taking its effect, low dosage, and low by-effect.

Description

Drug excipient---potassium alginate and composition of medicine thereof
[technical field] the present invention relates to a kind of new drug excipient---potassium alginate and all kinds of blood pressure lowerings, the blood fat lowering composition medicine made as excipient by it.
[background technology] potassium alginate (Potassium Alginate) claims that again potassium alginate, its rational formula are (C 6H 7O 6K) n.This chemical compound has been public as food additive, but still meets reported in literature in the end as the medicine excipient.Although alginic acid, sodium alginate are done the excipient of medicine in a lot of countries, and are written into European Pharmacopoeia, in the local medicine will in American Pharmacopeia and Liaoning, owing to be subjected to traditional view constraint restriction, potassium alginate never has the people it is used as the medicine excipient.
The eighties initial stage, seen the bibliographical information that relevant potassium alginate can suppress the spontaneous hypertension white mouse hypertension effect of high sodium feed, related content is documented in the paper of a piece of the border Sargassum meeting of eight or three young island countries " 10N-EXCHANGE AND HYPOTENSIVE EFECTS OF POTASSIUNALGINATE IN RATS ON HIGH SODIUM DIET " by name.This paper is explained the blood pressure lowering mechanism of having chatted potassium alginate: in the time of in potassium alginate enters stomach, gastric acid becomes alginic acid with potassium alginate; Alginic acid enters in the intestinal at first and the sodium ion combination, along with feces is got rid of external.Animal experiment shows that the sodium excretion amount in the feed potassium alginate group rat feces is apparently higher than matched group.This blood pressure lowering mechanism is different from the depressor of present disclosed all categories, therefore can regard potassium alginate as a class novel depressor.
Relevant potassium alginate also has a lot of reports, in the CN1095307A application for a patent for invention description, discloses the marine alga food for decreasing fat that a kind of main component is oligomeric potassium alginate.It is 2~5 that the flat 6-237783A of JP discloses a kind of degree of polymerization, and molecular weight is the sour potassium in 100~1800 daltonian brown seas, and this potassium alginate only is suitable for adding to a kind of health food of preparation in the food.In the ZL96114651.6 patent documentation, disclosing a kind of viscosity is 1~20 centipoise, and molecular weight is 2000~50000 potassium alginate, mainly is used as antihypertensive drugs, health food and food.
The potassium alginate that the present invention relates to, for above-mentioned patent documentation open before promptly public chemical compound.Doing food additive during the sixties abroad uses, test according to the inventor, viscosity all has the effect of inhibition hypertension in various degree to spontaneous hypertension rat (SHR) at 40 centipoises, 60 centipoises, 80 centipoises, 120 centipoises, 150 centipoises (above viscosity data is all measured with rotary viscosity method commonly used), therefore, this document is mentioned the potassium alginate that potassium alginate is a general reference, is not subjected to keeping within bounds of above-mentioned patent documentation.
The report of alginic acid, alginate (comprising potassium alginate) blood fat reducing also begins to see the sixties, the inventor utilizes the SD rat test, finds that viscosity all has the trend that SD rat plasma cholesterol levels and triglyceride level are reduced at the potassium alginate of 10,20,40,80,120,150 centipoises (these data all record with the rotary viscosity method).
Yet, how to make this natural ocean blood pressure lowering of potassium alginate, blood fat reducing active substance be able to better application, thereby it is faster to obtain onset, better effects if, safety is higher, side effect still less, more economical, the convenient blood pressure lowering of using, the blood fat reducing medicine.The inventor has done a large amount of formula combination and experimental study to this, find that therefrom potassium alginate can participate in the prescription with two kinds of identity, and a kind of is the medicine excipient; A kind of is new depressor.This hypotensor, the inventor is referred to as the depressor of " digestive tract row sodium class ".
[summary of the invention] the objective of the invention is to overcome the deficiency of above-mentioned prior art and a kind of drug excipient is provided---potassium alginate and composition of medicine thereof.
Above-mentioned purpose of the present invention is accomplished by following technological means.
A kind of drug excipient can use as adjuvant, emulsifying agent, suspending agent, thickening agent in preparation, it is characterized in that said drug excipient is a potassium alginate, and its rational formula is (C 6H 7O 6K) n.This excipient can adopt the potassium alginate of any molecular weight section, any range of viscosities, makes various Western medicine preparations and Chinese medicine preparation with any medicament mixed.
The toxicological study of relevant potassium alginate; national public health of Holland and environmental conservation institute toxicologic study chamber; existing penetrating elaboration the before 30 years drafted in the 17 meeting that ADI value is that per kilogram of body weight 50mg (in alginic acid) as seen is very safe material in the food.Discriminating item in study of pharmacy and inspection item, comprising transparency, sulfate, loss on drying, residue on ignition, heavy metal, the chemical examination of arsenic salt item prove the complete conformance with standard of potassium alginate.Do the tablet of adjuvant with potassium alginate, the test of disintegration also meets the requirements fully.
In sum, illustrate that potassium alginate is a kind of complete satisfactory medicine excipient.
A kind of composition of medicine that contains above-mentioned potassium alginate excipient component is characterized in that containing in the said composition of medicine 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 a kind of or more than one combination in any of diuretic component, the weight of above-mentioned depressor component is 0.001%~100% of potassium alginate composition weight.
A kind of composition of medicine that contains said components; it is characterized in that containing in the said composition of medicine Chinese medicine depressor; this depressor be Pheretima, Radix Scutellariae, Radix Aristolochiae, one or more of bone, Herba Plantaginis, trailing plants cloth Folium Cannabis, green tangerine, Herba Leonuri, Calculus Bovis, Margarita, Flos Chrysanthemi component form Chinese traditional compound medicines, the weight of above-mentioned depressor component is 1%~200% of potassium alginate composition weight.
A kind of composition of medicine that contains said components, it is characterized in that containing in the said composition of medicine lipid lowerers component, this lipid lowerers is to examine rare amine, colestipol, the Lip river is cut down him and is ordered, generally cut down him and order, plug cuts down him and orders, probucol, nicotinic acid, inositol niacinate, acipimox, the chloroethene spy, bezafibrate, Etofylline Clofibrate, non-unconcerned Bei Te, gemfibrozil, pantethine, or active skull cap components ovum phosphoric acid, polyenoic acid, one or more combination in any of Ginkgo biloba extract (flavonoid glycoside and terpene lactones) component, the weight of above-mentioned lipid lowerers component is 0.001%~100% of potassium alginate composition weight.
According to country's " drug approval way " regulation, the acidic group of medicine is changed into sodium salt or potassium salt or changes a kind of sodium salt of medicine into potassium salt, should treat by similar medicine.Sodium alginate and potassium alginate belong to the sodium salt and the potassium salt of alginic acid together, and the excipient that therefore is equivalent to be identified can be done the adjuvant, excipient, emulsifying agent, suspending agent, ropiness increasing agent of preparation etc.Therefore, potassium alginate can be made various dosage forms with any medicament mixed.The present invention utilizes potassium alginate to substitute traditional sodium alginate as drug excipient, not only can play kalium replenishment row sodium effect to human body, and can utilize the blood pressure lowering mechanism of potassium alginate, with all kinds of Western medicine preparations or the mutual compatibility of Chinese medicine preparation, make blood pressure lowering, the blood fat lowering composition medicine of newtype.The above-mentioned composition of medicine that contains the potassium alginate component, compare with one-component potassium alginate medicine, have advantages such as drug effect is fast, dosage is little, drug action is lasting, the present invention has overcome in the prior art simple with the shortcoming that potassium alginate is slow as the existing onset of antihypertensive drugs, taking dose is big, and can alleviate the toxic and side effects of existing Western medicine preparation or Chinese medicine preparation simultaneously.This potassium alginate participates in pharmaceutical formulation as excipient and has dual function, and the combined therapy effect obviously improves, and safety is reliable.
[specific embodiment] embodiment one: make composition of medicine with depressor and potassium alginate, the depressor composition weight that contains in this composition of medicine is 0.005%~60% of a potassium alginate composition weight.Above-mentioned depressor can adopt beta-blocker, but as the standing clinical depressor propranolol hydrochloride 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, plug ground Luo Er, bisoprolol, Tartaric acid metoprolol, alprenolol, times Ta Leer, esmolol, acebutolol, amosulalol, labetalol, dilevalol, arotinolol, Carvedilol, Celiprolol.
Beta-blocker side effect and untoward reaction be usually as seen: anxious, neurotic, maincenter depression, dreaminess, illusion, vomiting, headache, cardiopalmus, tachycardia, weak, tremble, perspiration, anorexia, feel sick, stomachache, vomiting, serious hypertension.
The blood pressure lowering mechanism of beta-blocker is optionally to combine with beta receptor in the adrenoceptor, hinders the noradrenergic nerve mediator to combine with beta receptor, the generation adrenolytic.Cardiac insufficiency, asthma, peripheral blood vessel spasm, hypoglycemia, bradycardia, the careful usefulness of atrioventricular block person.
Make composition of medicine with above-mentioned any one or more than one beta-blocker and potassium alginate, the beta-blocker depressor composition weight that contains in this composition of medicine is 0.001%~10% of a potassium alginate composition weight, can obviously reduce the side effect of beta-blocker depressor component.
Embodiment two, and clinical normal selection diuretic and B-receptor blocking agent share, to alleviate the hypokalemia that some diuretic is caused.Clinical trial, the patient who takes metoprolol adds potassium alginate, antihypertensive effect more than single much better with one side, can improve sleep state significantly, and dreaminess, illusion, symptom such as anxious also obviously weaken.Take 100 milligrams of diuretic and B-receptor blocking agents former every day, can change into and take 50 milligrams every day, potassium alginate is to take 3 gram amounts every day by taking 6~8 gram quantitative changes every day.The part by weight configuration arbitrarily of diuretic and B-receptor blocking agent.
Conclusion: still put into practice from theory and to verify that all potassium alginate can use with diuretic and B-receptor blocking agent compatibility.Characteristics: to the remarkable blood pressure lowering blood pressure of hypertensive patient, do not cause orthostatic hypotension and electrolyte disturbance, the follow-up continuation of insurance of drug withdrawal maintained an equal level steady blood pressure 4-6 days, obviously alleviated epigastric discomfort, asthenia and parahypnosis etc.
Embodiment three: calcium antagonist is the very potential depressor of a class, calcium antagonist commonly used at present has nifedipine, nicardipine, nitrendipine, nimodipine, amlodipine, niludipine, isradipine, Buddhist nun's comet Horizon, Felodipine, darodipine, SKF-102362, Manidipine, lacidipine, benidipine, barnidipine etc.
The blood pressure lowering 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, free calcium ion concentration descends in blood vessel wall and the myocardial cell slurry because it can make, myocardial contraction weakens and is the negativity muscular strength and uses, reduce cardiac muscle power consumption oxygen consumption, expansion peripheral vessels, blood pressure reduce, and cardiac load alleviates.
Take the common side effect of calcium antagonist headache, dizziness, erubescence, hypotension, numb limbs and tense tendons, nausea and vomiting, weak etc. are arranged.
Clinical trial, nifedipine and potassium alginate are used, and can obtain windfall effect.
1, side effect obviously alleviates, the original numb limbs and tense tendons of patient, feel sick, vomiting, anesthesia such as weak, the headache and dizzy symptom is improved, should should be mentioned that especially, some male patient takes calcium ion antagonist for a long time such as nifedipine (nifedipine), Norvasc (amlodipine) etc. can cause sexual hypofunction even forfeiture, and after being used with potassium alginate, sexual function can be restored.
2, can obtain rapid-actionly, not have the effect of bounce-back, after the drug withdrawal, can keep 4~5 days blood pressure lowering state, go up gradually after the week, see following one group of data (mmHg of blood pressure unit):
Time Before taking 24 hours 2 weeks 4 weeks After the drug withdrawal 2 days After the drug withdrawal 4 days
Swelling pressure relaxes 102 92 85 83 86 90
Systolic pressure 185 150 140 132 135 142
Annotate: be the meansigma methods of test group n=12.
3, make the dosage of nifedipine and potassium alginate be reduced to half amount respectively.
Patient's folk prescription is taken four of 10mg sheet nifedipines every day; Folk prescription is taken potassium alginate (water content 15%) every day needs 6~8 gram/skies.After both share, nifedipine two meters every day 20mg, potassium alginate gram every days 3.
4, the lipid level of having a blood test after the treatment, T-CHOL and triglyceride level all are significant reduction.
Make composition of medicine with above-mentioned any one or more than one calcium antagonist and potassium alginate, this composition of medicine can make up with the foregoing description, forms new compound recipe Chinese-western medicine preparation.
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, alacepril, thunder end Puli, quinapril, delapril hydrochloride, cilazapril, benazepril, TA-6366 is arranged, accompanies diindyl Puli etc.
Blood pressure lowering mechanism: feritin is a kind of proteolytic enzyme, and it is former to be secreted into the vasoconstriction that liver is produced behind the blood---a kind of feritin substrate of alpha globulin 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, thereby suppressing kassinin kinin brings high blood pressure down, hypertension by due to the renal vascular disease all responds to ACEI, and general essential hypertension 60-70% has the blood pressure lowering reaction.This hypotensor is less than the depressor side effect of other classification, common having choke cough, erythra, heating etc.Angiotensin converting enzyme inhibitor is many to be share with diuretic, makes effectiveness strengthen, reduce hypokalemia due to the latter, and diuretic can reduce blood volume, increase Na +Drain, the two is used, total effective rate can reach 80-85%.Make composition of medicine with above-mentioned any one or more than one angiotensin converting enzyme inhibitor and potassium alginate, this composition of medicine can make up with the foregoing description, forms new compound recipe Chinese-western medicine preparation.
Clinical trial: select primary hypertension patient 32 people, by age, after the pairing of the sex and the state of an illness, be divided into two groups at random, every group 16 people, take for one group and take 3 of captopril (formal name used at school captopril) 20mg sheet every days, another group 1.5 of captopril 20mg sheet every days, potassium alginate 3-4 every day gram, experimental result sees the following form:
Figure A0210987500071
Annotate: the mmHg of blood pressure unit is effective, obvious effective rate is evaluated standard rating with depressor
Embodiment five: potassium alginate and vasodilator combination
A lot of classes are arranged in the vasodilator: because the energy blood vessel dilating weakens the blood circulation Peripheral resistance, cardiac load alleviates, blood pressure drops.Common have a following kind: 1) directly act on the vascular smooth muscle medicated bag and draw together the hydralazine of expansion artery, the Yin handkerchief peace of rattling away; The nitre Pu Na of expansion artery and vein; Expansion of veins.2) α beta blocker.3) ganglioplegic.4) calcium antagonist.5) angiotensin converting enzyme inhibitor.6) blocade such as reserpine behind the intersection neuroganglion.7) other.Wherein 4), 5) narrating specially before this.
Each classification of the common adverse effect of this type of medicine is had nothing in common with each other again, with blocker reserpine behind the intersection neuroganglion, this type of drug effect is slow, the amplitude that blood pressure reduces is also undesirable, but this hypotensor is safe and reliable, reserpine is used for FUFANG JIANGYA PIAN decades, is hyperpietic's medicine commonly used so far, and xerostomia, nasal obstruction phenomenon can appear in user once in a while.
FUFANG JIANGYA PIAN is equipped with diuretic, anti-allergic drug and multivitamin and forms based on reserpine, if reserpine and potassium alginate compatibility are used, antihypertensive effect obviously strengthens.Make composition of medicine with above-mentioned any one or more than one vasodilator and potassium alginate, this composition of medicine can make up with the foregoing description, forms new compound recipe Chinese-western medicine preparation.
The characteristics of this compound recipe Chinese-western medicine preparation are: rapid depressurization, do not rebound, untoward reaction and side effect be little.
Embodiment six: potassium alginate and diuretic combination
Diuretic generally is not listed in the depressor scope in classification, take but middle effect diuretic thiazide is commonly used for depressor, and the depressor compatibility of normal and other class uses.
Mention above, mainly at digestive tract row sodium, diuretic then is to act on ascending thick limb of Henle's loop to potassium alginate, influences Na +, CI -Active transport, thereby be loop diuretic again.
Potassium alginate and diuretic drug combination can improve the hypokalemia that is caused by diuretic, from medullary loop and the two-way row's sodium of digestive tract, can strengthen antihypertensive effect.Make composition of medicine with above-mentioned diuretic and potassium alginate, the diuretic composition weight that contains in this composition of medicine is 0.001%~50% of a potassium alginate composition weight.
Embodiment seven: potassium alginate and the combination of other depressor
The depressor of other type such as cental system depressor etc. can make up with potassium alginate.The cental system depressor composition weight that contains in this composition of medicine is 0.002%~80% of a potassium alginate composition weight.Present embodiment can make up with the foregoing description, forms new compound recipe Chinese-western medicine preparation.
Embodiment eight: potassium alginate and the Chinese medicine composition that hypotensive effect is arranged
Some Chinese medicine has hypotensive effect, as Pheretima, Radix Scutellariae, Radix Aristolochiae, bone, Herba Plantaginis, trailing plants cloth Folium Cannabis, green tangerine, Herba Leonuri, Calculus Bovis, Margarita, Flos Chrysanthemi 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 composition of medicine is 30%~80% of a potassium alginate composition weight.Present embodiment can make up with the foregoing description, forms new compound recipe Chinese-western medicine preparation.
Embodiment nine: potassium alginate and lipid lowerers combination.
Lipid lowerers commonly used examine come rare amine, colestipol, Lip river cut down he order, general cut down he order, fill in cut down that he orders, probucol, nicotinic acid, inositol niacinate, acipimox, chloroethene spy, bezafibrate, Etofylline Clofibrate, non-unconcerned Bei Te, gemfibrozil, pantethine component any one or more than one.The lipid lowerers composition weight that contains in the combinations thereof medicine is 0.005%~99% of a potassium alginate composition weight.
Embodiment ten: potassium alginate and the active skull cap components that effect for reducing fat is arranged, and as polyenoic acid, lecithin, the combination of Ginkgo biloba extract (flavonoid glycoside and terpene lactones) component any one or more than one.Contain natural blood fat reducing active component in this composition of medicine, weight is 10%~70% of potassium alginate composition weight.

Claims (5)

1, a kind of drug excipient can use as adjuvant, emulsifying agent, suspending agent, thickening agent in preparation, it is characterized in that said drug excipient is a potassium alginate, and its rational formula is (C 6H 7O 6K) n.
2, a kind of composition of medicine of excipient component according to claim 1 that contains is characterized in that containing in the said composition of medicine 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 a kind of or more than one combination in any of diuretic component, the weight of above-mentioned depressor component is 0.001%~100% of potassium alginate composition weight.
3, a kind of composition of medicine of excipient component as claimed in claim 1 or 2 that contains; it is characterized in that containing in the said composition of medicine Chinese medicine depressor; this depressor be Pheretima, Radix Scutellariae, Radix Aristolochiae, one or more of bone, Herba Plantaginis, trailing plants cloth Folium Cannabis, green tangerine, Herba Leonuri, Calculus Bovis, Margarita, Flos Chrysanthemi component form Chinese traditional compound medicines, the weight of above-mentioned depressor component is 1%~200% of potassium alginate composition weight.
4, a kind of composition of medicine of excipient component as claimed in claim 1 or 2 that contains, it is characterized in that containing in the said composition of medicine lipid lowerers component, this lipid lowerers is to examine rare amine, colestipol, the Lip river is cut down him and is ordered, generally cut down him and order, plug cuts down him and orders, probucol, nicotinic acid, inositol niacinate, acipimox, the chloroethene spy, bezafibrate, Etofylline Clofibrate, non-unconcerned Bei Te, gemfibrozil, pantethine, or natural blood fat reducing active component polyenoic acid, ovum phosphoric acid, one or more combination in any of Ginkgo biloba extract (flavonoid glycoside and terpene lactones) component, the weight of above-mentioned lipid lowerers component is 0.001%~100% of potassium alginate composition weight.
5, composition of medicine according to claim 3, it is characterized in that containing in the said composition of medicine lipid lowerers component, this lipid lowerers is to examine rare amine, colestipol, the Lip river is cut down him and is ordered, generally cut down him and order, plug cuts down him and orders, probucol, nicotinic acid, inositol niacinate, acipimox, the chloroethene spy, bezafibrate, Etofylline Clofibrate, non-unconcerned Bei Te, gemfibrozil, pantethine, or natural blood fat reducing active component polyenoic acid, ovum phosphoric acid, one or more combination in any of Ginkgo biloba extract (flavonoid glycoside and terpene lactones) component, the weight of above-mentioned lipid lowerers component is 0.001%~100% of potassium alginate composition weight.
CN02109875A 2002-05-28 2002-05-28 Medicinal excipient-potassium alginate and its composition Pending CN1461656A (en)

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WO2014190935A1 (en) * 2013-05-30 2014-12-04 苏州科景生物医药科技有限公司 Multi-functional composition and preparation method and application thereof
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CN101104649B (en) * 2006-07-12 2011-05-18 谭攸恒 Potassium alginate and composition thereof
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