CN104222999A

CN104222999A - Composition, preparation and application of novel low sodium salt

Info

Publication number: CN104222999A
Application number: CN201410505408.4A
Authority: CN
Inventors: 于传兴; 李德山
Original assignee: DALIAN AVITAL BIOTECHNOLOGY Co Ltd
Current assignee: DALIAN YATE SALT INDUSTRY CO., LTD.
Priority date: 2014-09-26
Filing date: 2014-09-26
Publication date: 2014-12-24
Anticipated expiration: 2034-09-26
Also published as: CN104222999B; WO2016045309A1

Abstract

The invention discloses low-molecular potassium alginate containing low sodium salt. The low sodium salt contains the low-molecular potassium alginate and sodium chloride, wherein the weight-average molecular weight of the low-molecular potassium alginate is 700-10,000 dalton, value of the molar ratio of a mannuronic acid unit to a guluronic acid unit in the low-molecular potassium alginate is 0.3-3.3, and ubbelohde viscosity of the low-molecular potassium alginate is 3-16; the weight ratio of the sodium chloride to the low-molecular potassium alginate is (48-83):(13-40). According to the invention, as the low sodium salt contains the low-molecular potassium alginate, functions of potassium supplement and sodium excretion are realized; as the low-molecular potassium alginate contains small molecular potassium alginate, in the intestinal canal, the small molecular potassium alginate can be converted into small molecular sodium alga acid which is absorbed via an intestinal mucosa to enter a blood vessel, and as the small molecular sodium alga acid has the function of a calcium channel retardant, blood pressure drops. The low sodium salt contains the low-molecular potassium alginate, which is used for prevention and aid therapy of primary hypertension.

Description

A kind of composition of Novel low-sodium salt, preparation and purposes

Technical field

The present invention relates to a kind of Cardia Salt containing oligomeric potassium alginate and preparation and purposes.

Background technology

People be unable to do without salt as you know.The main component of salt is sodium chloride.Sodium chloride exists with the form of sodium ion and chlorion in human body.Sodium chloride is taken in too much can bring out hypertension again, causes the various diseases such as coronary heart disease, cerebral infarction, renal dysfunction, PVR, has a strong impact on everybody quality of life even life-span.According to investigations in China's Adult Groups of 35-74 years old, Prevalence of Hypertension reaches 27.2%.China is hypertensive to be known ,cure and control situation is troubling: in existing patient, and the person that knows condition-inference is less than 45%, and person is no more than 30% to take depressor, only has the people's blood pressure less than 10% to obtain stability contorting.The patient of 45% is had to apply loss of weight, limit salt, non-drug therapy such as limit wine, exercise etc.Wherein, limit salt is most popular method, mend potassium with minimum.Expert points out to show from 3 national hypertension investigation in the past and result of study analysis and assessment, and achieve noticeable achievement although China's Hypertensive Population is prevented and treated, illness rate and absolute number still all present a rapidly rising trend.

Essential hypertension is one of most common disease threatening human health, and its pathogenesis is illustrated not yet completely.Research shows that essential hypertension pathogenesis is lost compensatory relevant with the blood pressure regulating mechanisms caused by individual inheritance background and the effect of multiple acquired environment factor, wherein mainly comprises the factors such as the activation of Renin-Angiotensin System (RAS), the absorption of high sodium, insulin resistance and spiritual nerve.

At present, hypertensive treatment comprises Non-medicine intervention and drug therapy two aspect.Antihypertensive drugs conventional clinically mainly contains six large classes: diuretics, α blood ARBs, calcium channel blocker, Angiotensin-Converting (ACE) inhibitor, β press down ARBs and Angiotensin Ⅱ receptor antagonist.Curative effect and the bad reaction situation interindividual variation of antihypertensive drugs are very large.Non-medicine intervention mainly through limiting the intake of salt, rational diet, lose weight, the method such as motion regulates blood pressure, to a certain degree reduce hypertensive cardiovascular complication and occur.

Fitness guru calls people to eat salt less, mainly in order to allow everybody take in sodium in salt less.Present people eat salty mostly, and meat outeat, dish eat like a bird.Also hide stealthy salt in many packaged foods, talk the absorption of high sodium, the sodium of 80% is taken in from finished product food, is easy to the problem causing " the low potassium of high sodium " like this, causes the numerous diseases such as hypertension.From this angle, Cardia Salt is " health salt " really.Cardia Salt potassium instead of part sodium, therefore can reduce the absorption of sodium to a certain extent, increases the absorption of potassium, helpful to the potassium balance of maintenance body's sodium.At present, Cardia Salt, is be raw material with salt compounded of iodine, then with the addition of a certain amount of potassium chloride and magnesium sulfate, thus improve sodium (Na in body ⁺), potassium (K ⁺), magnesium (Mg ²⁺) poised state, preventing hypertension.Some producers have produced Cardia Salt now, to expect the intake reducing sodium chloride.In Cardia Salt, sodium chloride has lacked, and adds potassium chloride.In some Cardia Salt, KCE content is unexpectedly up to 20-35g/100g.

Alginate is existing application on pharmaceutical preparation.Potassium alginate (C6H7O8K) n forms primarily of the sylvite of alginic acid.Alginic acid relies on Isosorbide-5-Nitrae-glycosidic bond to connect and the copolymer be made up of different GGGMMM fragment by α-α alginic acid mannuronic acid (M unit) from β-β alditol guluronic acid (G unit).The concentration (G:M ratio) of G and M acid determines the characteristics such as different structures and biocompatibility.In the alginic acid (such as brown alga) that nature exists, the molar ratio of G and M is 0.2 to 2.5, and molecular weight is 100,000 to 1,500,000 dalton.The alginate that China produces is mainly raw material with sea-tangle.

US 2009/0104330 discloses the low sodium salty composition for reducing the sodium chloride in food.Said composition contains at least one at least one, amino acid and the amino-acid salt in sodium chloride, food acids and food hydrochlorate, and can contain potassium chloride, yeast extract, sweetener and spices in addition.Said composition allegedly has the metallic taste/bitter taste of reduction, strengthens the intensity of saline taste characteristic and raising saline taste.Although list the technology of the many preparation said compositions when needing greater or lesser particle, can find out that said composition is prepared by the direct fusion of component.Because food acids, amino acid, yeast extract, sweetener and the perfume additive added in the sodium chloride base product in US 2009/0104330 has the granularity being significantly less than sodium chloride and potassium chloride in fact usually, therefore, estimate that the composition as made in US 2009/0104330 is as above explained easily separately, such as when transporting and store, this produces the product with the composition different from expection, and this affects again the function of said composition.

Summary of the invention

The object of this invention is to provide a kind of Cardia Salt containing oligomeric alginate.

Cardia Salt provided by the present invention, containing sodium chloride and oligomeric potassium alginate, wherein, the weight average molecular weight of described oligomeric potassium alginate is 700 dalton-10,000 dalton, Ubbelohde viscosity 3-16 and in described oligomeric potassium alginate the molar ratio of mannuronic acid unit and guluronic acid units be 0.3-3.3.

Preferably, the weight average molecular weight of the described low ALG in oligomeric potassium alginate of the present invention is 1,000-4,500 dalton, and in described low ALG, the molar ratio of mannuronic acid unit and guluronic acid units is 0.4-3.3.

The raw material being generally used for preparing above-mentioned low ALG is brown alga.Various brown alga can as the raw material producing alginic acid, such as sea-tangle, water cloud, tawny daylily algae, pelvetia silquosa, sargassum etc.Consider that cost is preferred, one or more in sea-tangle, kelp, bulk kelp and sargassum (as half leaf sargassum, flax leaf sargassum).

The method of the above-mentioned low ALG of preparation provided by the invention comprises conventional degradation step.Such as, preferably, described method comprises weight average molecular weight is 10,000-1,500,000 daltonian alginic acid is degraded, and described degradation step comprises one or more degradation step in mechanical degradation step, photochemical degradating step, immobilised enzymes degradation step and chemical degradation step.Further, before described degradation step, carry out one or more degradation step in mechanical degradation step, photochemical degradating step, immobilised enzymes degradation step and oxidative degradation step.Described mechanical degradation step, photochemical degradating step, immobilised enzymes degradation step and oxidative degradation step are known in this field, be documented, be all incorporated herein by reference here in PCT/CN99/00202.Such as physical step comprises ultrasonic wave process or high speed shear process; Photochemical step utilizes light radiation and catalysis to process; Oxidative degradation step comprises use organic oxidizing agent and/or inorganic oxidizer, as hydrogen peroxide, Peracetic acid, potassium peroxide, peroxidating potash, potassium perborate (sodium), potassium permanganate, ammonium persulfate, potassium hydrogen persulfate double salt, potassium chlorite, sodium chlorite etc.; After immobilised enzymes degradation step comprises and uses porous soda-lime glass ball carrier to fix alginic acid catabolic enzyme, dress post decomposes.

Described oligomeric potassium alginate is that above-mentioned low ALG obtains with the potassium ion neutralization reaction of alkalescence.Described oligomeric sodium alginate is that above-mentioned low ALG obtains with the sodium ion neutralization reaction of alkalescence.

The invention provides a kind of Cardia Salt containing potassium alginate, comprise described oligomeric potassium alginate and sodium chloride.

The weight ratio of described sodium chloride and oligomeric potassium alginate is (48-83): (13-40).

In a technical scheme of the present invention, in described Cardia Salt, also comprise oligopeptide.

Described oligopeptide is marine alga oligopeptide, maize oligopeptide or shellfish oligopeptide.

The mass ratio of described sodium chloride, oligomeric potassium alginate and oligopeptide is (48-83): (13-40): (3.8-11.5).

Also additive is comprised in described Cardia Salt, described additive is selected from taste improving compounds, taste masked agent, mineral matter, anti-caking agent or flowing additive, one or more any combination in taste improving compounds, taste masked agent, mineral matter, anti-caking agent and flowing additive; Described sodium chloride, oligomeric potassium alginate, oligopeptide and additive weight ratio are (48-83): (13-40): (3.8-11.5): (0.2-0.5).

Described additive accounts for the 0.2%-0.5% containing alginate Cardia Salt gross weight.

Described taste masked agent is selected from following substances: edible organic acid; Amino acid and derivative thereof; Yeast; Yeast extract; From the protein hydrolysate in yeast extract and so on source; Peptide; Hydrolyzed vegetable protein; Hydrolyzed fat; Ribonucleotide; Flavonoids; The acid amides of amino acid and dicarboxylic acids; One in trehalose and gluconate or two or more any combination; Or their combination;

Described taste improving compounds is selected from one or more any combination in following substances: derived from spices oleoresin and the oil of any one in allspice, sweet basil, capsicum, cassia bark, cloves, fennel seeds, dill, garlic, marjoram, nutmeg, pimiento, black pepper, rosemary and turmeric; Essential oil; Tangerine oil; Garlicky spices; Plant extracts; Protein hydrolysate; Natural and artificial potpourri, and react by the Mei Lade type between reduced sugar and protein derived component the processed flavors made; Described mineral matter (trace element) calcium, magnesium, zinc, chromium, iron, molybdenum, copper, manganese all add with the form of alginate.

Described Cardia Salt is the particle of the particle diameter with 250 microns to 1 millimeter.

The preparation method of described Cardia Salt pulverizes the Cardia Salt particle obtaining the particle diameter with 250 microns to 1 millimeter after comprising the salt granulating powders using the oligomeric potassium alginate being greater than 150 microns to stick below 50 micron granularities or the pressure compacting re-using 40 to 100MPa.

Present invention also offers the method preparing described oligomeric alginate, the method comprises prepares low ALG according to above-mentioned method, then makes the Cardia Salt containing oligomeric potassium alginate (sodium).

The preparation method of a kind of Cardia Salt provided by the invention; comprise the steps: according to described constituent mass ratio, it is that to stick granularity be the Cardia Salt particle that the rear pulverizing of pressure compacting that the sodium chloride powder granulation of less than 50 microns re-uses 40 to 100MPa obtains the granularity with 250 microns to 1 millimeter for the sodium chloride powder granulation of less than 50 microns or the oligomeric potassium alginate that uses granularity to be greater than 150 microns that the oligomeric potassium alginate using granularity to be greater than 150 microns sticks granularity.

In a technical scheme of the present invention, the preparation method of of the present invention kind of Cardia Salt, comprise the steps: according to described component ratio, be spray oligopeptide solution in the oligomeric alginate powder of 258-270 micron at d50, the NaCl powder that d50 is 39-50 micron is added, granulation on comminutor after mixing, dry, use the sieve of 280 microns, sieve the Cardia Salt obtained containing oligomeric potassium alginate and oligopeptide. and determine to have the d50 of 498-640 micron; Be left behind NaCl and contain the Cardia Salt sample of oligomeric potassium alginate and oligopeptide for preparation next time.

In a technical scheme of the present invention, the preparation method of Cardia Salt, comprise the steps: according to described component ratio, mix after d50 is spray oligopeptide solution in the oligomeric potassium alginate powder of 258-270 micron, add the NaCl powder that d50 is 39-50 micron, granulation on comminutor, uses the pressure of 40 to 100MPa to manufacture pellet on Herzog tablet press machine by the mixture obtained; Then resulting pellet is diametrically broken, and the Cardia Salt particle of the d50 with 398-520 micron is obtained in screen mill grinding screening.

In a technical scheme of the present invention, the preparation method of Cardia Salt, comprise the steps: according to described ratio of weight and number, oligomeric alginate and oligopeptide and all the other components except sodium chloride are mixed with into dry weight and count the oligomeric alginate of 20% and the composition solution of oligopeptide, it is 60 ~ 80 DEG C according to the composition solution temperature of oligomeric alginate and oligopeptide, hydrojet speed 25 ~ 35 ls/h, it is 630 microns of Cardia Salt samples that sodium chloride fine 12-25 kilogram being less than 600 microns for diameter carries out to sodium chloride fine the d50 that dressing obtains containing oligomeric alginate and oligopeptide by fluidized drying, described fluidized drying condition adopts the end to spray the composition solution of oligomeric alginate and oligopeptide or the top spray composition solution for oligomeric alginate and oligopeptide.

The application of above-mentioned Cardia Salt in the product preparing prevention or assisting in treating hypertension is also in protection scope of the present invention.

The present invention proves by experiment, oral potassium chloride, because potassium ion has diuresis, a part of sodium ion is excreted through kidney, the potassium ion of oligomeric potassium alginate has same diuretic effect with the potassium ion of potassium chloride, low ALG has the effect of the sodium ion absorbed in intestinal fluid, large intestinal juice, and this is that potassium chloride does not have.

The results showed, oligomeric (low molecule) potassium alginate not only has mends the effect of potassium row sodium, because containing Small molecular potassium alginate in oligomeric (low molecule) potassium alginate, change into Small molecular sodium alginate at its Small molecular alginic acid of enteron aisle and can absorb intravasation through intestinal mucosa, Small molecular sodium alginate has calcium ion channel blocker effect, and blood pressure is declined.Oligomeric potassium alginate is on the impact (see embodiment) of drinking high level salt solution rat, observe oligomeric potassium alginate freely to drink rat and add oligomeric potassium alginate (0.1%) solution of 5% ratio after 60 days according to 2% salting liquid, oligomeric potassium alginate has no obvious impact to animal ingestion amount and amount of drinking water, but clearly can increase urine volume and obviously alleviate rat body weight, the systemic humoral amount caused by the slimming effect of oligomeric potassium alginate may increase with urine volume reduces relevant simultaneously.In addition, the oligomeric potassium alginate of above-mentioned consumption significantly can increase urine sodium and kaliuresis amount, significantly can increase serum potassium simultaneously, and has no obvious impact to excrement sodium and the excretion of excrement potassium and Serum Na+ concentration.Confirm that oligomeric potassium alginate can play in vivo and mend the effect of potassium row sodium.

Oligomeric potassium alginate Hypotensive Mechanism is at least urinated with the diuresis and increasing by test product, the effect of ight soil sodium excretion amount is relevant.Oligomeric potassium alginate is applicable to the crowd needing to mend potassium and have cardiovascular and cerebrovascular disease to be inclined to.

Large production-scale oligomeric potassium alginate sample is pressed body weight 60Kg and is calculated, and take 1 day, each 2.8 grams, aided blood pressure-lowering effect can reach national health food required standard completely.The antihypertensive effect half-life longer (can reach 144 hours), the oligomeric potassium alginate of large-scale production adds (as: salt, dairy produce, flavouring etc.) in varieties of food items to, day dose be not more than 6.0 grams in salt.Can delicate flavour be increased containing after the Cardia Salt interpolation oligopeptide of oligomeric potassium alginate, make Cardia Salt become salty fresh flavouring, can more by the welcome of consumer.

When after food direct oral cavity, stomach protopepsia, be drained into small intestine by the motion of stomach.At small intestine, hydrochloric acid in gastric juice is neutralized by the sodium acid carbonate in pancreatic juice, for the effect of the various enzymes of small intestine provides suitable alkaline environment.As maximum in amylopsin activity when pH value is 6.9-7.0; Trypsase activity when pH value is 8 is maximum.So in small intestine, food obtains and decomposes thoroughly, and protein, starch, fat are broken down into amino acid, glucose, aliphatic acid and glycerine.

Potassium alginate oral administration enters in stomach, and gastric juice pH is 1-3.5 potassium alginate and hydrochloric acid in gastric juice effect, forms gel, potassium ion major part absorbs intravasation rapidly by small intestine, alginic acid enters after small intestine through stomach, and the sodium acid carbonate in pancreatic juice forms a part for intestinal fluid, and intestinal fluid pH value is 7.8-8.0.Large intestinal juice pH value is 8.3-8.4, and the sodium acid carbonate effect of alginic acid and intestinal juice neutral and alkali, changes into sodium alginate, through colon, rectal absorption moisture, the sodium alginate changed at rectum alginic acid becomes a part for ight soil, is excreted, and achieves to mend potassium row and receive.

Detailed description of the invention

Percentage composition in following embodiment or embodiment is weight percentage if no special instructions.

The object of this invention is to provide a kind of Cardia Salt containing oligomeric potassium alginate.

Cardia Salt provided by the present invention, containing sodium chloride and oligomeric potassium alginate, wherein, the weight average molecular weight of described oligomeric potassium alginate is 700 dalton-10,000 dalton, Ubbelohde viscosity 3-16 and in described alginic acid the molar ratio of mannuronic acid unit and guluronic acid units be 0.3-3.3.

In the present invention, oligomeric potassium alginate is that the weight average molecular weight of the low ALG of sylvite of low ALG and the molar ratio of mannuronic acid unit (M) and guluronic acid units (G) can measure by the method that this area is conventional, such as, make low ALG product and the alkali substance reaction (such as NaOH) of alginic acid degraded gained, obtain the soluble-salt of low ALG, utilize the mini DAWN TREOS laser light scattering instrument of Wyatt company of the U.S. (WTC) and the 150c of Waters, US, PL220c and ALLIANCE 2000 is according to operation instructions, measure the molecular weight and the molecular weight distribution that obtain low ALG, and calculate weight average molecular weight.The molar ratio measuring mannuronic acid unit and guluronic acid units can adopt chemical method, acid hydrolysis is carried out to sample, make into single mannuronic acid unit and the mixture of guluronic acid units, anion exchange resin is utilized to adsorb, wash-out, can separate the mixture of mannuronic acid unit and guluronic acid units, through colour developing, absorbance total under surveying mannuronic acid unit and guluronic acid units 485nm respectively, by calculating the molar ratio that can obtain G and M.Also the content of monomer in G, M, GG, MM, GM in alginic acid can be measured with nuclear magnetic resonance method (NMR).

The method of above-mentioned molecular weight determination is viscosimetry.Viscosimetry determining molecular weight, equipment needed thereby is comparatively simple, and operation is more easily grasped, and as surveyed Ubbelohde viscosity, is usually used in the molecular weight determination of polysaccharide.Viscometric molecular weight measures, working sample inherent viscosity η before this, then by conversion equation, i.e. empirical formula η=KM ^acalculate molecular weight.Ubbelohde viscometer: capillary pipe length is 140 ± 5nm, internal diameter 0.5 ± 0.05nm, B ball volume is 3.35 ± 0.5mL, and at 25 DEG C, measuring the delivery time with distilled water should between 120 ~ 180 second.With the delivery time of stopwatch Accurate Determining solution.Read each concentration (C ₁, C ₂, C ₃) delivery time, temperature during test generally adopts the water bath with thermostatic control of 25 ± 0.05 DEG C.Oligomeric potassium alginate adopts Ubbelohde viscometer viscosimetric to control mean molecule quantity exactly.The pH value of potassium alginate in the distilled water solution of 1% is about 7.3.The degree of polymerization (DP) and molecular weight directly related with the viscosity of potassium alginate solution.

Described oligomeric potassium alginate is that the alkali compounds neutralization reaction of above-mentioned low ALG containing potassium obtains.

In a preferred version, the weight ratio of the sodium chloride in Cardia Salt of the present invention and oligomeric potassium alginate is (48-83): (13-40); If concrete scope can also be (64-77): (15-22), (64.6-76.9): (15.38-22).Concrete, described sodium chloride accounts for the 48%-83% of described Cardia Salt gross weight, and that concrete can be 64.6-76.9%.Described oligomeric potassium alginate accounts for the 13-40% of described Cardia Salt gross weight; That concrete can be 15.38-22%.

The material of described sodium chloride-containing can from several different sources, such as sea salt, rock salt, refining (vacuum) salt or synthesis salt source.

Also additive is comprised in described Cardia Salt, described additive is selected from taste improving compounds, taste masked agent, mineral matter, anti-caking agent or flowing additive, one or more any combination in taste improving compounds, taste masked agent, mineral matter, anti-caking agent and flowing additive; Described additive accounts for the 0.2%-0.5% containing alginate Cardia Salt gross weight.

Described sodium chloride, oligomeric potassium alginate, oligopeptide and additive weight ratio are (48-83): (13-40): (3.8-11.5): (0.2-0.5).Concrete weight ratio can be (64-77): (15-22): (5-8): (0.2-0.5), can also be (64.6-76.9): (15.38-22): (5.8-7.76): (0.2-0.5).

In this application, Cardia Salt product is defined as both comprising following product: wherein a part of sodium chloride is replaced (in this article also referred to as sodium chloride alternative materials by oligomeric potassium alginate, such as oligomeric potassium alginate) substitute the product of (material in such an implementation, containing sodium chloride and sodium chloride alternative materials is referred to as " material of sodium chloride-containing "); This product can contain the product of at least one additive (such as flavoring agent, odor mask, nutrient or other additive any) simultaneously; Comprise again following product: produce strong saline taste sensation, to guarantee to experience with the sodium chloride of relatively low amount the product based on sodium chloride of identical taste effect by adding the additive serving as so-called flavoring agent; And the combination of upper two kinds of products.Substantially dry refers in this application based on (always) solid, have lower than 3 % by weight, preferably lower than 1 % by weight free water content.Free water refers to can (from particle) any water of evaporating at 100 DEG C.

Cardia Salt of the present invention also can comprise additive, described additive is selected from suppression, enhancing, impact in one embodiment or changes the material of taste and/or local flavor, or affects this product salt and maybe can use the caking character of the food of product salt of the present invention, flow freely the material of character, color, quality, microbial stability, smell or nutritive value.Described additive preferably can be derived from the synthetic additive of natural origin for the additive synthesized.

In a more preferred embodiment, this additive be taste/flavour enhancer (taste improving compounds), taste/local flavor screening agent (such as sheltering the taste beastly (bitter taste or metallic taste) of sodium chloride alternative materials), anti-caking agent or flowing additive.In the most preferred embodiment, this additive is taste/flavour enhancer or taste/local flavor screening agent.Due to this two classes taste strengthen and taste masked agent usually overlapping, they are referred to as " flavoring agent " simply in this article.

Flavoring agent can be selected from material well known by persons skilled in the art.The example being suitable as the material of flavoring agent is found in such as WO 2004/075663.

In one embodiment, above-mentioned taste/flavour enhancer or taste/local flavor screening agent can be selected from the group be made up of following substances: edible organic acid, such as butanedioic acid, citric acid; Amino acid and derivative thereof, such as glutamate/ester; Yeast; Yeast extract; From the protein hydrolysate in yeast extract and so on source; Peptide; Hydrolyzed vegetable protein; Hydrolyzed fat; Ribonucleotide; Flavonoids; The acid amides of amino acid and dicarboxylic acids; Trehalose; Gluconate; Other flavor enhancement or local flavor Auto-regulator; Or their combination.Other example comprises organic acid, such as lactic acid, malic acid; Organic acid salt; The salt of ribonucleotide; Such as, from product and the fermented food of Maillard reaction, beans sauce, alec, sardine and cheese.

Described flavor enhancement is well known by persons skilled in the art, and term flavor enhancement comprises spices oleoresin derived from any one in allspice, sweet basil, capsicum, cassia bark, cloves, fennel seeds, dill, garlic, marjoram, nutmeg, pimiento, black pepper, rosemary and turmeric and oil; Essential oil, comprises fennel oil, caraway oil, caryophyllus oil, eucalyptus oil, fennel oil, garlic oil, oil of ginger, peppermint oil, onion oil, Zanthoxylum essential oil, rosemary oil and peppermint oil; Tangerine oil, such as orange oil, lemon oil, bitter orange oil and Oleum Citri Reticulatae; Garlicky spices, comprises garlic, leek, chives and onion; Plant extracts, comprises arnica extract, anthemidis flos extract, lupulus extract and pot marigold extract; Plant perfume extract, comprises blackberry, blueberry, cichory root, cocoa, coffee, cola, Radix Glycyrrhizae, cynarrhodion, sassaparilla root, foreign sassafrases bark, tamarind, Radix Glycyrrhizae and vanilla extract; Protein hydrolysate, comprises hydrolyzed vegetable protein (HVPs), meat protein hydrolysate, milk protein hydrolyzates; Natural and artificial potpourri, and processing (reaction) spices made is reacted by the Mei Lade type between reduced sugar and protein derived component (comprising amino acid).

Representational independent flavor enhancement comprises one or more any combination in benzaldehyde, diacetyl (2,2-diacetyl), vanillic aldehyde, ethyl vanillin and citral (3,7-dimethyl-2,6-octadiene aldehyde).

In one embodiment, other additive can be added in this product salt.In a preferred embodiment, this type of other additive can be selected from by vitamin, acid, yeast, amino acid, functional additive or nutrient such as fluoride, iodide, iodate, mineral matter, nitrite, nitrate, flavor enhancement, spices, sugar, (natural) flavoring, spices or vanilla.

In a technical scheme of the present invention, Cardia Salt of the present invention contains sodium chloride (NaCl), oligomeric potassium alginate and oligopeptide; Described oligopeptide is marine alga oligopeptide, shellfish oligopeptide or maize oligopeptide or their any combination.The weight ratio of described sodium chloride, oligomeric potassium alginate and oligopeptide is (48-83): (13-40): (3.8-11.5); Concrete weight ratio can be (64-77): (15-22): (5-8), can also be (64.6-76.9): (15.38-22): (5.8-7.76).Concrete, described oligopeptide can account for the 3.8%-11.5% of described Cardia Salt gross weight.

Above-mentioned oligopeptide is the enzymolysis product of native protein, and wherein, marine alga oligopeptide is the enzymolysis product of Sargassum protein, and shellfish oligopeptide is the enzymolysis product of shellfish protein, and maize oligopeptide is the enzymolysis product of zein.Marine alga and shellfish oligopeptide.Oligopeptide can increase delicate flavour, also has aided blood pressure-lowering effect.

In addition, because the additive added in sodium chloride base product has the granularity less than sodium chloride raw material, particularly like this when they relate to organic additive except oligomeric potassium alginate.Such as, yeast based additive has the granularity far below 100 microns, and industrial available sodium chloride has the granularity of hundreds of microns usually.If mix this bi-material, can be separated with during storage in transport.Agglomeration is the mode avoiding this layering.But in compacting with after being crushed to desired particle size, comparatively small-particle appears on particle external surface, thus causes additive losses.

In addition, because many additives have the character different with sodium chloride alternative materials from sodium chloride, therefore, from machining angle, be more preferably and avoid their major parts to be positioned on the outer surface of final products.Such as, oligomeric potassium alginate is than sodium chloride moisture absorption, so that the character of more moisture absorption when product salt shows when additive particles is arranged on outer surface than they embeddings and is evenly mixed in whole product salt.Therefore, a technical scheme of the present invention finds out more effectively and produces the method not having the improvement of the even Cardia Salt product of above-mentioned shortcoming.We have been found that now more effectively and produce the method with the improvement of the Cardia Salt product of the taste of improvement, wherein additive and sodium chloride and optional sodium chloride alternative materials Homogeneous phase mixing be included in individual particles.Method of the present invention just can improve the characteristic of anti-moisture absorption by the surface that the composition that oligomeric potassium alginate adds oligopeptide is coated in sodium chloride particulate.

Cardia Salt product of the present invention is preferably made up of free-pouring particle.As pulverising step comprises any method reducing particle size, and the method comprising such as fragmentation, crush or grind and so on.

It is noted that component can be that wherein two or more pulverize together in a combining step, or pulverized by independent pulverising step.If use sodium chloride alternative materials in the method, it can pulverize or pulverize separately together with sodium chloride.

Pressing step comprises any method making particle agglomeration by applying external force, is applied pressure (causing certain density of the particles mixture of compacting) in the unidirectional compacting of pellet for suppressing the pressure of particles mixture.But, can suppress suitably by other press (such as roll compactor).In these cases, pressure used is the pressure causing the compacts density identical with unidirectional compacting.Pressing step comprises any method making particle agglomeration by applying external force, such as, by carrying out applying external force and make particle agglomeration under the pressure of 40 to 100MPa.

The inventive method can contain subsequent step in one embodiment, and wherein screening materials is to isolate the particle of required composition, or by the particle of desired particle size range.

Concrete, Cardia Salt product has the granularity of 250 microns to 1 millimeter, pulverizes and obtain oligomeric potassium alginate and salt particles mixture after the salt granulating powders using the oligomeric potassium alginate being greater than 150 microns to stick below 50 micron granularities or the pressure compacting re-using 40 to 100MPa; To produce the particle with the desired particle size of 250 microns to 1 millimeter; Wherein under the condition of substantially dry, carry out these steps.

The product obtained by the method in fact with additive evenly being mixed in the particle of sodium chloride-containing is feature, and there is good separating resistance and wear resistence.

In an embodiment of the invention; oligomeric potassium alginate powder (d50 is 258-270 micron) is sprayed marine alga oligopeptide solution; (d50 is 39-50 micron to add NaCl powder after mixing; granulation on comminutor; dry; use the sieve of 280 microns, sieve the Cardia Salt obtained containing oligomeric potassium alginate and marine alga oligopeptide.And determine the d50 with 498-640 micron.Be left behind NaCl and contain the Cardia Salt sample of oligomeric potassium alginate and marine alga oligopeptide for preparation next time.

In yet another embodiment of the present invention; mix after oligomeric potassium alginate powder (d50 is 258-270 micron) is sprayed marine alga oligopeptide solution; (d50 is 39-50 micron to add NaCl powder; granulation on comminutor, uses 1.0t/cm by this mixture on Herzog tablet press machine ²pressure (being equivalent to the pressure of IOO MPa) manufactures 50 grams of pellet (40 mm dias, 20 height).Resulting pellet is diametrically broken, and on Frewitt screen mill, use the sieve grinding of 6 millimeters, 3 millimeters and last 1 millimeter.Use the sieve of 710,500,280 and 90 microns that the product from this Frewitt screen mill is sieved into fraction.Further analysis fraction 280 to 710 microns (namely merging two fractions) also determines the d50 with 398-520 micron.

In an embodiment of the invention, oligomeric potassium alginate and oligopeptide and all the other components except sodium chloride are mixed with into dry weight and count the oligomeric potassium alginate of 20% and the composition solution of oligopeptide, it is 40 ~ 60 DEG C by the composition solution temperature of charge of oligomeric potassium alginate and oligopeptide, 60 ~ 80 DEG C, 80 ~ 100 DEG C, hydrojet speed 20 ~ 25 ls/h, 25 ~ 35 ls/h, 35 ~ 40 ls/h are screened, result: when the composition solution temperature of charge of oligomeric potassium alginate and oligopeptide is 40 ~ 60 DEG C, temperature of charge is too low, powder is not easily dry, easy caking.Hydrojet speed is 20 ~ 25 ls/h, and hydrojet speed is low, and flow is little, affects efficiency.Hydrojet speed is 35 ~ 40 ls/h, and hydrojet speed is fast, and powder is not easily completely dry, easily lumps.When temperature of charge is 80 ~ 100 DEG C, temperature of charge is too high, may cause the decomposition of active ingredient in composition intermediates.Therefore select the composition solution temperature of charge of oligomeric potassium alginate and oligopeptide to be 60 ~ 80 DEG C, concentration 20%, sodium chloride fine 12-25 kilogram that hydrojet speed 25 ~ 35 ls/h is less than 600 microns for diameter carries out functional potassium alginate layering pelletization by fluidized drying condition to sodium chloride fine.Fluidized drying condition have employed end spray potassium alginate marine alga peptide combinations liquid respectively, and the d50 containing oligomeric potassium alginate marine alga peptide that top spray potassium alginate marine alga peptide combinations liquid all can obtain stay in grade is 630 microns of Cardia Salt samples.The weight ratio of its sodium chloride, oligomeric potassium alginate and oligopeptide is (48-83): (13-40): (3.8-11.5).Concrete weight ratio can be (64-77): (15-22): (5-8), can also be (64.6-76.9): (15.38-22): (5.8-7.76).

Being prepared as follows of above-mentioned marine alga oligopeptide in the present invention: adopt enzyme hydrolysis method, exogenous enzymes technology.

Protein digestion engineering is completed jointly by endopeptidase and exopeptidase.The former hydrolysate is polypeptide, the hydrolysate of the latter is free amino acid, so improve hydrolysis ability by adding restriction endonuclease or adding excision enzyme again, kinds of protein in different hydrolysis material and Amino acid profile ratio different, therefore the selection of enzyme and the hydrolysising condition of enzyme also have obvious difference, and exogenous enzymes technology can be divided into single zymolysis technique, two enzyme resolving tech and multienzyme complex enzyme hydrolysis technology.

(1) single enzyme resolving tech list enzyme process to be only hydrolyzed to the protein in raw material by a kind of exogenous enzymes to obtain the method for protein hydrolysate.Adopt each hydrolysising condition of Optimized by Orthogonal Test, determine bacillus subtilis neutral proteinase for best, degree of hydrolysis 60-62.6%.

(2) two enzyme resolving tech single enzyme is always limited to the hydrolysis of protein, if therefore select two kinds of enzymes protein substrate enzymolysis specificity being had to complementation, can obtain good hydrolysis effect.Utilize bacillus subtilis neutral proteinase and pepsin two kinds of exogenous enzymes hydrolysis marine alga undaria pinnitafidas, percent hydrolysis can reach 68.0%.

Utilize the white enzyme of pawpaw and alkali protease two kinds hydrolysis marine alga sea-tangle dish, percent hydrolysis can reach 69.0%.

(3) multienzyme complex enzyme hydrolysis technology multienzyme composite algorithm is the method be hydrolyzed to material protein with two or more enzymes.Adopt multienzyme complex enzyme hydrolysis technology, first carry out short time hydrolysis with mixing endopeptidase, heat up after to make that proteolysis becomes peptide section, structure fluffs loose the enzyme that goes out, add flavor protease (Flavourzyme) again and carry out second stage enzymolysis under its suitable condition, degree of hydrolysis can reach 68.2%, and hydrolyzate has unique delicious local flavor.Multi-enzyme method can utilize the effect selectivity of multiple protein enzyme to make material protein fully be hydrolyzed into amino acid and end peptide, and the delicious amino acid of generation and peptide can make the taste of hydrolyzate more delicious.

Hydrolysis time is on the impact of hydrolyzing seaweed rate

Fixing hydrolysis temperature is transferred to 50 DEG C, when ceteris paribus, controls different hydrolysis time, be abscissa with hydrolysis time, in sample liquid, amino acid content is ordinate, and result can be found out, hydrolysis time is hydrolyzed in confused situation aobvious in 2 ~ 4 hours window, and percent hydrolysis raises slowly.Along with the prolongation of hydrolysis time, amount of amino acid accumulates gradually, and after reaching 4 hours when hydrolysed, percent hydrolysis raises rapidly, and after 6 hours, ramp-up rate slows down to some extent.After certain hour, amino acid concentration builds up to larger concentration, continue hydrolysis again, amino acid whose content increase is very micro-, and this may be that newly-generated amino acid is less, and the amino acid produced more easily secondary change occurs along with the prolongation of time, thus the amino acid decreased in hydrolyzate, also there is Maillard reaction simultaneously, also consumes the amino acid in product, the amino acid content in product is declined.Find that the hydrolysis hydrolyzate of 5,6 hours is more better than other several groups in color and fragrance by subjective appreciation, synthesise various factor is considered, when amino acid builds up to Cmax, should stop hydrolysis, avoid side reaction occurs, but overlong time can affect the organoleptic quality of product.Can determine that hydrolysis time controlled at 6 hours more suitable.Utilize ultrasonic pretreatment enzymolysis substrate, hydrolysis efficiency can be significantly improved.

Further, present invention also offers above-mentioned Cardia Salt in preventing hypertension or the application prepared in the product of preventing hypertension or food.

Conventional technology is used from 1998 Nian Qi Dalian Yaweite Biotechnology Co., Ltd., as heat drop solution, oxidizing process, sonication, acid degradation method, alginic acid cracking enzyme process is used singly or in combination and alginic acid large for molecular weight is degraded into the little low ALG of molecular weight, then obtains oligomeric potassium alginate with the alkali neutralization containing potassium.Effort through 10 years makes the technology of the oligomeric potassium alginate of preparation ripe day by day, find under the efficient condition of maintenance step-down by pharmacodynamic experiment over 10 years, along with the Ubbelohde viscosity of potassium alginate sample declines, to the amount minimizing of the potassium alginate that spontaneous hypertension rat is fed, the oligomeric potassium alginate Ubbelohde viscosity of Dalian Yaweite Biotechnology Co., Ltd.'s development is 3-16.Multinomial animal experiment, prove that oligomeric potassium alginate has the effect of mending potassium row sodium really, its effect is better than potassium chloride far away.

The present invention proves by experiment, oral potassium chloride, because potassium ion has diuresis, a part of sodium ion is excreted through kidney, the potassium ion of potassium alginate has same diuretic effect with the potassium ion of potassium chloride, alginic acid has the effect of the sodium ion absorbed in intestinal fluid, large intestinal juice, and this is that potassium chloride does not have.

Large production-scale oligomeric potassium alginate sample is pressed body weight 60Kg and is calculated, and take 1 day, each 2.8 grams, aided blood pressure-lowering effect can reach national health food required standard completely.The antihypertensive effect half-life longer (can reach 144 hours), the oligomeric potassium alginate of large-scale production adds (as: salt, dairy produce, flavouring etc.) in varieties of food items to, and day, dose was in 6.0 grams, sodium chloride.Can delicate flavour be increased containing after the Cardia Salt interpolation marine alga oligopeptide of potassium alginate, make Cardia Salt become salty fresh flavouring, can more by the welcome of consumer.

Potassium alginate oral administration enters in stomach, and gastric juice pH is 1-3.5 potassium alginate and hydrochloric acid in gastric juice effect, forms gel, potassium ion major part absorbs intravasation rapidly by small intestine, alginic acid enters after small intestine through stomach, and the sodium acid carbonate in pancreatic juice forms a part for little Intestinal liquid, and intestinal fluid pH value is 7.8-8.0.Large intestinal juice pH value is 8.3-8.4, and the sodium acid carbonate effect of alginic acid and intestinal juice neutral and alkali, changes into sodium alginate, through colon, rectal absorption moisture, the sodium alginate changed at rectum alginic acid becomes a part for ight soil, is excreted, and achieves to mend potassium row and receive.For the crowd of chronic renal failure being not suitable for potassium alginate, oligomeric sodium alginate secondary buck is adopted to be suitable selection.

Embodiment

The preparation of embodiment 1, oligomeric potassium alginate

Oligomeric potassium alginate take sodium alginate as raw material, with after hcl acidifying, sodium alginate is changed into alginic acid in ethanol, make solvent with water again after isolating acidic ethanol, do pH value regulator with potassium hydroxide, alginic acid is changed into the sylvite of alginic acid, its chemical reaction is as follows:

C ₅H ₇O ₄COONa+HCl＝C ₅H ₇O ₄COOH+NaCl

C ₅H ₇O ₄COOH+KOH＝C ₅H ₇O ₄COOK+H ₂O

1. production process:

1) sodium alginate pre-treatment (conversion reaction); 2) degraded salify; 3) polishing purification; 4) evaporation and concentration; 5) drying and granulating (oligomeric potassium alginate).

2 charge ratios

Sodium alginate: ethanol: hydrochloric acid=1.0:1.5:0.5

Alginic acid: ingredient water: hydrogen peroxide: potassium hydroxide: active carbon=1.0:6.0:0.4:0.4:0.1

3 technology conditions

A conversion reaction: soak time 10-12h;

B degradation reaction: temperature=85 DEG C ± 8 DEG C, time=90 ~ 120min;

C salt-forming reaction: potassium hydroxide solution concentration=35 ~ 40%, reaction temperature≤reaction DEG C;

4 quality requirements

A degradation reaction thing viscosity (Ubbelohde viscosity)≤20;

PH value=7.5 ~ 8.0 of b salt-forming reaction thing;

5 methods of operating

A. transform: when feeding intake, after first adding ethanol, restart agitator, then add sodium alginate and add hydrochloric acid more on request and stir rear immersion 10-12 hour, acidic ethanol is separated.

B. degrade: first add 5 times when feeding intake to the distilled water of alginic acid, add the hydrogen peroxide of 3% concentration again, start agitator, add alginic acid again, in reactor interlayer, pass into steam simultaneously and heat, until when the temperature of reactant reaches the temperature of regulation, start timing and carry out degradation treatment, keep reaction temperature and the inspection by sampling after the time of regulation, dynamic the stirring of the viscosity number of reactant is less than Ubbelohde viscosity 20, and degradation treatment completes.

C. salify: after degradation treatment terminates, cooling water is passed in reactor interlayer, make the temperature of reactant, when dropping to the requirement of salify temperature, just can slowly add pH regulator solution in reactant, carry out salt-forming reaction, the pH value of measured reaction thing at any time in course of reaction, until stop adding alkali when pH value reaches stable 7.5 ~ 8.0, adds alginic acid lyases, by potassium alginate dry weight basis, every 10 kilograms add alginic acid lyases liquid 10 liters.The Rate activity of alginic acid lyases is that 1800U/MG cracking temperature controls at 40 DEG C, reacts 5 hours.

D. de-taste decolouring: measure by the volume (L) of the potassium alginate solution after salify, add the active carbon of 1%, heats to 60 DEG C ~ 70 DEG C maintenances 60 minutes, can send next procedure by blowing under the condition stirred.

E. polishing purification

The aqueous solution of last process gained potassium alginate, the insoluble polyvalent metal alginates that generate in course of reaction (as, Ca, Fe, Pb operation etc.) and alginate fibre, the foreign material such as active carbon, removing should be separated by the method for filtering, thus obtain purer potassium alginate solution.

F. evaporation and concentration

The potassium alginate aqueous solution that polishing purification process obtains carries out concentration, and the solid content of solution is improved.Select equipment vacuum evaporimeter (JMZ200) evaporation and concentration temperature: 50 DEG C ~ 70 DEG C; Concentrate concentration: >=20%; Concrete operation method is:

A () checks whether use equipment works well, and after all are errorless, first equipment is carried out the pre-heat treatment, and then carries out concentration operation by rated condition charging.

B () operates by the operation instruction of device therefor and points for attention, filtrate is concentrated to concentration: send next procedure for subsequent use after >=20% concentration.

G. drying and granulating

Concentrated potassium alginate solution seasoning is made potassium alginate fine powder, is placed in after nature drops to room temperature, then is wetting agent with pure water, make 40 ~ 250 object particulate powder with granulating drier, obtain oligomeric potassium alginate.Wherein, drying and granulating technology condition: dry: EAT=160 DEG C ~ 180 DEG C, leaving air temp=80 DEG C ~ 90 DEG C; Granulate: temperature controls to operate under the condition of 50 ~ 60 DEG C.

The preparation of oligomeric Na-alginate take sodium alginate as raw material, with after hcl acidifying, sodium alginate is changed into alginic acid in ethanol, make solvent with water again after isolating acidic ethanol, do pH value regulator with NaOH, other technique used, equipment is the same with the oligomeric potassium alginate of preparation.

After testing, the oligomeric potassium alginate Ubbelohde viscosity of above-mentioned preparation is 3-16; Wherein average molecular weight is 700-10,000 dalton; The molar ratio of mannuronic acid unit and guluronic acid units is-0.3-3.3.

Oligomeric potassium alginate sample preparation becomes granule or powder. and calculate by body weight 60Kg, take 1 day, each 2.8 grams, aided blood pressure-lowering effect can reach national health food required standard completely.The antihypertensive effect half-life longer (144 hours can be reached), oligomeric potassium alginate to add in varieties of food items (as: dairy produce, flavouring etc.) wherein oligomeric potassium alginate take in the aided blood pressure-lowering standard that more than 2.8 grams all can reach national health food requirement.

Oligomeric potassium alginate ingestion experiment

Test crowd, select spontaneous hypertension patient, test crowd often organizes 30 people, ingest containing 35% potassium chloride Cardia Salt for control group, ingest every day containing 35% potassium chloride Cardia Salt 9.0 grams, wherein 5.9 grams, sodium chloride, 3.1 grams, potassium chloride. oligomeric potassium alginate of ingesting is test group, oligomeric potassium alginate 2.8 grams of ingesting every day.Ingest one month, every day all carries out test record to the systolic pressure of every ingester and diastolic pressure. and observed result lists following table 1-4 in.

Table 1. ordinary circumstance compares

The change of table 2. systolic pressure is compared (mmHg, )

The change of table 3. diastolic pressure is compared (mmHg, )

Project	Before test-meal	In test-meal	Difference	After test-meal	Difference
						Embodiment 1	97.40±9.64	91.27±8.11***	6.13±8.00	86.55±11.05***	10.82±10.59

Table 4. antihypertensive effect compares

Grouping	Reciprocal	Effective	Effectively	Invalid	Total effective rate (%)
						Embodiment 1	30	10	15	5	83.33

Embodiment 2, brown alga pancreatin hydrolysis legal system are for marine alga oligopeptide

For the marine alga undaria pinnitafida of brown algae Laminariaceae, composed as follows: moisture 15-18, protein 10-16, fatty 1-2, carbohydrate 38-45 (about containing alginic acid 20), fiber 2-3.Ash content 18-30.Marine alga contains asparatate 3.40 as the natural traditional food of one, leucine 2.72, lysine 1.34, alanine 2.7, proline 1.48 etc.Except above-mentioned various nutritional labeling, also containing a large amount of iodine and other various soluble metal microelement kind nutritional labeling.

1. the preparation of marine alga

Marine alga raw material is poured in the stainless steel reaction pot of sandwich after crushed, add 5% acetum submergence marine alga, soak 24h to dissolve acid-soluble material wherein, subsequently acetic acid is discharged from the bottom discharge pipe being enclosed with multilayer gauze, then inject deionized water and repeatedly soak.The acetic acid that cleaning down remains is neutrality to the pH of solution, adding deionized water makes the weight ratio of marine alga and water be about 1: 20, vapours is passed into subsequently in the interlayer of double-deck reaction pot, raise water temperature to 80 DEG C in pot, then the automatic stirrer in reaction pot is opened, slowly add 10%NaOH solution while stirring, adjust pH value of solution to be 8.0, stir continuously until the marine alga in reaction pot in the pasty state.

Heating and the object adding alkali are: l) kill the bacterium in solution, prevent bacterial reproduction in enzymolysis process and the nutrition that reduces Sargassum protein matter is worth; 2) because marine alga is water insoluble, but can be dissolved in hot alkaline solution, therefore add NaOH solution and can play hydrotropy effect; 3) heat and alkali effect can make marine alga generation sex change, and the space structure of protein changes, and peptide interchain chemical bond ruptures, and is easier to by proteases for decomposing; 4) adjust the pH of solution, make pancreatin play maximum bioactivity.

2. enzyme digestion reaction

Maintain the temperature at least half an hour of solution 80 DEG C in reaction pot, then pass into running water by interlayer and reduce solution temperature to 50 DEG C in pot, pancreatin (Sichuan Deebio Pharmaceutical Co., Ltd. 10 of requirement is added by 3% of marine alga dry weight, 000U/g), under agitator stirs continuously, start enzyme digestion reaction, the quantity of steam that period adjustment passes into reaction pot interlayer makes temperature maintain 50 DEG C.In enzyme digestion reaction process, in particularly enzyme digestion reaction early stage, due to the hydrolysis of pancreatin, the albumen of marine alga is constantly decomposed generation polypeptide, and polypeptide continues the peptide being decomposed into short chain, even under amine peptase or aminopeptidase effect, generates a small amount of free amino acid.Because polypeptide, little peptide or amino acid are ampholytes, the most slant acidity of isoelectric point, so in course of reaction, the pH value increasing whole reaction system with the peptide generated gradually can constantly reduce, for ensureing that the maximum bioactivity of pancreatin makes the pH of reactant liquor maintain 8.0, this just needs constantly in reactant liquor, to add NaOH weak solution.Terminate from adding pancreatin enzyme digestion reaction after 6h.Now, the intake strengthening steam makes enzymolysis liquid be warming up to 80 DEG C and maintains 30min, and its effect has be by pancreatin deactivation with enzymolysis reaction at two: one; Two is again kill miscellaneous bacteria in reactant liquor to prevent bacterial multiplication in processing procedure subsequently.

3. filtration treatment

Enzyme digestion reaction liquid filters through plate and frame filter press and micro-filtration compressor respectively.The filter membrane of plate and frame filter press strengthens fixing thickening filter paper by two thickness cotton gauzes, and adopt pore size filter to be 0.5 μm of quartzy filter core in micro-filtration compressor, the two crosses the pancreatinum particle filtered compared with coarsegrain in reactant liquor.Before using plate and frame filter press, be first pressed into clear water with distilled water from filtered fluid intake channel, ensure do not have water to spill from its elsewhere, to prove that plate and frame filter press in order except cleaner liquid outlet.Before using micro-filtration compressor, first quartzy filter core is put in 5%NaOH weak solution and cleans, then wash down with distilled water, to ensure best filter effect.

Add 10% hydrochloric acid in enzymolysis liquid after filtration to neutralize, regulate enzymolysis liquid to neutral.In order to promote that Sargassum protein dissolves, or for maintaining the stable of enzyme digestion reaction liquid pH value in enzymolysis process, add the NaOH of a great deal of, changed into a large amount of sodium chloride by hydrochloric acid neutralization subsequently, sodium chloride accounts for Sargassum protein weight ratio and has exceeded 10%.

4. concentrated, dry process

Carry out vacuum and low temperature through Vacuum Concentration pump to concentrate, moisture a large amount of in solution is evaporated under vacuum low-pressure, subsequently drying tower spraying dry, namely the small peptides finally obtaining the production of pancreatin hydrolysis Sargassum protein obtains marine alga oligopeptide.

Embodiment 3, papain are to the enzymolysis of Sargassum protein

Papain is to the enzymolysis of marine alga (sea-tangle) albumen, and temperature rises to 50 DEG C by 40 DEG C, and ammonia nitrogen stripping increases obviously.When temperature raises further, increase not obvious and have a declining tendency with temperature increase.This is because suitably heat, protein structure is loosened, exposes more enzyme action site, enzymatic activity also reaches the best use of state simultaneously, reduces gradually, cause amino nitrogen content also to reduce along with temperature continues to raise enzymatic activity.Therefore, we select 50 DEG C for the best use of temperature of hydrolysis.The maximum reaction temperature of enzyme is 60 DEG C, and under this temperature conditions, the enzyme of 70% that still keeps of temperature bath 100min is lived.Enzymolysis pH affects hydrolysising condition to enzyme digestion reaction: enzyme dosage 2.5%, solid-to-liquid ratio 1:3, time 6h, hydrolysis temperature 50 DEG C.Learn according to interrelated data, the optimum pH of papain, about 6.7, therefore, have chosen 6.25,6.5,6.75,7,7.255 levels.The enzymolysis result of papain to marine alga shows that the optimal reaction pH value of enzyme is 7.5, has good adaptability under the alkali condition of pH 9.0.The marine alga separation solution of 2.0-2.5% is after papain hydrolysis, and the free aminoacid contents such as serine, threonine, proline, histidine, methionine obviously increase, and the every 100ml of polypeptide improves 92-98mg.

The optimum hydrolysis technique of papain hydrolysis.Single factor experiment shows to be about 5h at enzymolysis time, concentration of substrate is 4%, enzyme concentration is about 5500U/g, pH value is in 7.0 ~ 7.5 scopes, and when temperature is 50 DEG C, papain hydrolysis effect is better.Orthogonal test shows, the impact order of 3 factors is: enzyme concentration > concentration of substrate > hydrolysis time; Optimum hydrolysis technique is: hydrolyzate pH value 7.5, and enzyme concentration is 5500U/g, and concentration of substrate is 4%, temperature 50 C, hydrolysis 6h, and degree of hydrolysis can reach 37.89% employing papain and is hydrolyzed and can obtains the enzymolysis liquid of higher degree of hydrolysis with this understanding.

The toxicity pharmacology pharmacodynamic test of embodiment 4, the oligomeric potassium alginate of the present invention

1, acute toxicity test: mouse, rat mtd test, oligomeric potassium alginate prepared by embodiment 1 is taken food at viewing duration to two kinds of sex mouse, rats, and drinking-water is movable normal, and without intoxicating phenomenon, fur light, without dead.Sample is all greater than 4.50g/kgBW to two kinds of sex mouse, rat oral maximum tolerated dose;

2, three genetic toxicity tests: 1) Salmonella reversion test: each dosage group return become clump count all do not exceed sample solvent control group return become clump count more than 1 times, also without dosage one reaction relation, to salmonella typhimurium TA97, TA98, TA100, TA102 tetra-strain test strain (Center for Disease Control of country of the Ministry of Public Health), adding with when not adding microsomal enzyme activation system, result is feminine gender, and result of the test can repeat.2) mouse marrow cell micro nuclear test: the ratio (PCE/NCE) of each dosage group two kinds of sex PCEMNRs and mature erythrocyte is between 1.25 ~ 1.36, and having no the bone marrow cell of sample to two kinds of sex mouse has obvious inhibitory action.Each dosage group two kinds of sex PCEMNR micronuclear rateses compare with sample solvent control group, there was no significant difference (P > 0.05), and endoxan group two kinds of sex PCEMNR micronuclear rateses compare with sample solvent control group, have significant difference (P < 0.01), having no sample has obvious damaging action to two kinds of sex mouse marrow cell chromosomes.

3, mouse inbred strain: each dosage group mouse sperm deformity rate compares with sample solvent control group, there was no significant difference (P > 0.05), and endoxan group mouse sperm deformity rate compares with sample solvent control group, have significant difference (P < 0.01), having no sample has obvious damaging action to Germ Cells of Male Mice.

Comprehensive above result of the test, draws conclusion (of pressure testing): the acute toxicity tests shows that oligomeric potassium alginate prepared by embodiment 1 is all greater than 4.50g/kgBW to two kinds of sex mouse, rat oral maximum tolerated dose.Three genetic toxicity tests are feminine gender, show the effect of oligomeric potassium alginate hereditary-less toxicity.

Oligomeric potassium alginate with high molecular potassium alginate for raw material through degraded obtain, degradation process is in fact also refine to go the impurity processes such as the carbohydrate of polyphenol, protein and complexity, and the oligomeric potassium alginate that oral process is refined can not produce allergic reaction.

The pharmacology pharmacodynamic experiment of embodiment 5, the oligomeric potassium alginate of the present invention

One, oligomeric potassium alginate is on the impact of rat ight soil row sodium amount

Method adopts tail pulses method of indirectly measuring blood pressure to measure SHRs systolic pressure, 40 rats are divided into 5 groups at random: blank Vehicle controls group, Aquazide H group (6.25mg/kg), oligomeric potassium alginate high dose, middle dosage and low dose group (500,250,100mg/kg), every day, gavage gave oligomeric potassium alginate, gave oligomeric potassium alginate 28d continuously; Measure blood pressure weekly, and the blood pressure of 3d, 6d after observing drug withdrawal.Collect SHRs rat ight soil for measure in ight soil containing sodium amount. result compares with the Vehicle controls group same period, successive administration 21d and 28d, and the SHRs blood pressure level of Hydrochioro and low molecule potassium alginate 3 dosage groups all reduces (P0.01); During drug withdrawal 3d and 6d, the hypotensive effect of 6.25mg/kg Hydrochioro disappears (P0.05); When drug withdrawal 3d, the systolic pressure of high, medium and low 3 the dosage groups of oligomeric potassium alginate is all lower than the Vehicle controls group same period (P0.05 or P0.01); During drug withdrawal 6d, 250 and 500mg/kg low molecule potassium alginate still can reduce SHRs blood pressure level (P0.01). the administration of conclusion oligomeric potassium alginate continuous oral can dose-dependently reduce SHRs blood pressure, and drug withdrawal 6d still presents lasting hypotensive effect, in, in high dose group ight soil there is significant difference than contrast 2 groups in the excretion of sodium.

Table 1. on the impact (1-5 days) of rat ight soil row sodium amount ( n=10)

* p < 0.05**p < 0.01 is contrasted with Hydrochioro than ☆ p < 0.05 ☆ ☆ p < 0.01 with model

Table 2. on the impact (6-10 days) of rat ight soil row sodium amount ( n=10)

Contrast with model ^*p < 0.05 ^*p < 0.01 and Hydrochioro are than ☆ p < 0.05 ☆ ☆ p < 0.01

Two, oligomeric potassium alginate is on the impact of drinking high level salt solution rat

1. material

1.1 animal used as test

Male SD rat, body weight 180-220g, is provided by Chengdu University of Traditional Chinese Medicine's animal center.Rearing conditions 20 ± 2 DEG C, 12h/12h circadian rhythm.Animal feeding in rat metabolism cage, feed of freely drinking water.

1.2 reagent

Oligomeric potassium alginate (low molecular weight potassium alginate, PA) prepared by embodiment 1, pale yellow powder, is dissolved in rat drinking water and freely drinks every day.

Sodium chloride (sodium chloride), white crystalline powder, lot number 20080928, Tianjin Zhi Yuan chemical reagent Co., Ltd, is dissolved in distilled water and prepares desired concn for rat and freely drink every day.

68% nitric acid (nitric acid), analyzes pure, colourless transparent liquid, lot number 20071108, and chemical reagent factory of glad Haixing County, Chengdu, is dissolved in distilled water the salpeter solution being mixed with 10% before use.For container without sodium process.

Nitric acid (nitric acid), top grade is pure, colourless transparent liquid, lot number 090211, and Sichuan Xilong Chemical Co., Ltd., is directly used in treatments of the sample.

Perchloric acid (perchloric acid), top grade is pure, colourless transparent liquid, lot number 20080708, and Tianjin orientalizes factory, is directly used in treatments of the sample.

1.3 instrument

SOLAA atomic absorption spectrophotometer: model M6, Thermo Elemental

Desk centrifuge: 4000 ~ 40000 revs/min, model TGL-16G, Town in Shanghai booth tech equipment factory.

Electric heating constant temperature tank: model DK-600, the grand experimental facilities Co., Ltd of upper Nereid.

Eppendorf adjustable pipette: 100-1000ul, German eppendorf company.

Finnpipette adjustable pipette: 20-200ul, finnpipette company of Finland.

Electronic balance: model BS210S, Beijing Sai Duolisi balance Co., Ltd.

Electronic balance: model BS3000, Shanghai Yousheng Balance Co., Ltd..

2. method

The preparation of 2.1 reagent

The preparation of 2.0%NaCl drinking water: take 25gNaCl and be dissolved in appropriate distilled water, be finally settled to 1250ml for subsequent use;

The preparation of 0.5%NaCl drinking water: get 2.0%NaCl drinking water 125ml, add distilled water and be settled to 500ml, to obtain final product;

The preparation of 2.0%NaCl/0.1%PA drinking water: take low molecule potassium alginate powder 0.625g, be dissolved in appropriate 2.0%NaCl drinking water, be finally settled to 625ml for subsequent use;

The preparation of 0.5%NaCl/0.025%PA drinking water: get 2.0%NaCl-PA drinking water 125ml, add distilled water and be settled to 500ml, to obtain final product.

The preparation of 10% salpeter solution: get 68% concentrated nitric acid solution 1000ml, add 5800ml distilled water, to obtain final product.

2.2 without sodium process

The metabolic cage tool of collection serum, urine sample and excrement sample, EP pipe, conical flask are soaked in 10% salpeter solution and spend the night, then uses deionized water drip washing dry for standby.

2.3 oligomeric potassium alginates are on the impact of rat water-electrolyte metabolism

40 SD male rats are divided into 5 groups at random: blank Vehicle controls group, 0.5%NaCl group, 2.0%NaCl group, 0.5%NaCl/0.025%PA group, 2.0%NaCl/0.1%PA group, often organize 8.The drinking water of each group is prepared according to the method for table 3.

Table 3. is group rat drinking water formulation respectively

Rat freely drinks water feed, measures rat 24h amount of drinking water, food ration, urine volume every day.Respectively raising the 0th, 30,60 days, tail venous blood sampling conventional separation of serum, leave and take rat 24h urine sample, excrement sample.Serum and urine sample save backup in-20 DEG C.The process of excrement sample: by ight soil in the drying after 12 hours of 60, pulverize, put in drier and save backup.

2.4 electrolytes determined methods

After experiment terminates, synchronous blind gets 100ul serum, is settled to 5ml with ultra-pure water; Get 50ul rat urine, with ultra-pure water constant volume 5ml; Take 0.1g ight soil in 50ml in conical flask without sodium process, add after 5ml red fuming nitric acid (RFNA) becomes white crystal with 0.5ml Perchloric Acid Digestion, add ultra-pure water and be settled to 10ml.Adopt Pulse sample introduction device to detect sodium, potassium content in serum, urine and excrement, calculate each group of rat blood serum sodium and serum potassium, and sodium, the potassium ion amount of draining in twenty-four-hour urine and ight soil.

Experimental result mean ± standard deviation (X ± s) represents, adopts SPSS11.5 software kit to carry out variance analysis to it, compares between two and adopt One-Way ANOVA inspection between group.The results are shown in Table 4 ~ 8.

3. result

3.1 oligomeric potassium alginate is on the impact of the general physical signs of rat

From table 4, at 60 days experimentations, compare with the blank Vehicle controls group same period, the body weight of 0.5%NaCl model group and 0.5%NaCl/0.025% oligomeric potassium alginate experimental group rat has no notable difference (P>0.05), but 2.0%NaCl model group rats body weight obviously reduces (P<0.01) after 30 days; Compare with 2.0%NaCl model group, 2.0%NaCl/0.1% oligomeric potassium alginate experimental group rat body weight obviously reduced (P<0.05) 60 days time.

From table 5, at 60 days administration process, compare with the blank Vehicle controls group same period, each treated animal food ration has no notable difference.

From table 5, compare with the blank Vehicle controls group same period, 0.5%NaCl model group urine volume has increase trend; 2.0%NaCl model group urine volume was significantly increased 30 days time, and presented 60 days time and necessarily tolerate phenomenon, and urine volume only has slight increase.Compare with the 0.5%NaCl model group same period, 0.5%NaCl/0.025% oligomeric potassium alginate experimental group rat urine volume does not have significant change; Compare with the 2.0%NaCl model group same period, 2.0%NaCl/0.1% oligomeric potassium alginate experimental group rat urine volume had increased slightly 30 days time, and clearly increased (P<0.01) 60 days time.

From table 5, compare with the blank Vehicle controls group same period, 0.5%NaCl model group and 0.5%NaCl/0.025% oligomeric potassium alginate experimental group rat amount of drinking water all do not have significant change, and 2.0%NaCl model group and 2.0%NaCl/0.1% oligomeric potassium alginate experimental group rat amount of drinking water have remarkable increase (P<0.01), wherein 2.0%NaCl/0.1% oligomeric potassium alginate experimental group amount of drinking water increased (P<0.05) apparently higher than 2.0%NaCl model group 30 days time.

3.2 oligomeric potassium alginates are on the impact of rat urine electrolyte excretion

Table 6 shows, when administration 60 days, compare with 0.5%NaCl model group, drinking mixed 0.5%NaCl/0.025% oligomeric potassium alginate experimental group rat urine sodium excretion amount has slight increase, when administration 30 and 60 days, the excretion of urine potassium also has increase trend, but difference does not all have statistical significance (P>0.05).

In addition, when 30 days and 60, the excretion of 2.0%NaCl model group rats urine sodium compares with Vehicle controls group obvious increase (P<0.05 or P<0.01), have increase trend during the excretion 60 days of urine potassium, but difference do not have statistical significance (P>0.05).Compare with 2.0%NaCl model group, 30 days time, drinking mixed 2.0%NaCl/0.1% oligomeric potassium alginate experimental group rat urine sodium excretion amount has increase trend, and 60 days time, have clearly increase (P<0.01); The excretion of urine potassium has obvious increase (P<0.05 or P<0.01) 30 days and 60 days.

3.3 oligomeric potassium alginate is on the impact of rat ight soil electrolyte excretion

From table 7, at 60 days experimentations, compare with the blank solvent group same period, drink merely 0.5% or 2.0%NaCl drinking water, and the oligomeric potassium alginate of drinking mixed 0.5%NaCl/0.025% or the excretion of 2.0%NaCl/0.1% low molecule potassium alginate drinking water on SD rat excrement sodium and excrement potassium do not affect.

3.4 oligomeric potassium alginates are on the electrolytical impact of rat blood serum

From table 8, at 60 days experimentations, compare with the blank solvent group same period, drink merely 0.5% or 2.0%NaCl drinking water, and the rat blood serum na concn of the oligomeric potassium alginate of drinking mixed 0.5%NaCl/0.025% or the oligomeric potassium alginate drinking water of 2.0%NaCl/0.1% do not have significant difference (P>0.01); When administration 60 days, compare with the model control group of drinking merely 2.0%NaCl drinking water, the rat blood serum potassium of the oligomeric potassium alginate of drinking mixed 2.0%NaCl/0.1% has conspicuousness to increase (P<0.01), but the serum potassium of other each experimental group does not have significant change.

4, brief summary

This experimental result shows: oligomeric potassium alginate has the regulating action of dosage correlation to the general physical signs of rat and electrolyte.

Freely drink rat and add oligomeric potassium alginate (0.1%) solution of 5% ratio after 60 days according to 2% salting liquid, oligomeric potassium alginate has no obvious impact to animal ingestion amount and amount of drinking water, but clearly can increase urine volume and obviously alleviate rat body weight, the systemic humoral amount caused by the slimming effect of oligomeric potassium alginate may increase with urine volume reduces relevant simultaneously.In addition, the oligomeric potassium alginate of above-mentioned consumption significantly can increase urine sodium and kaliuresis amount, significantly can increase serum potassium simultaneously, and has no obvious impact to excrement sodium and the excretion of excrement potassium and Serum Na+ concentration.

The oligomeric potassium alginate of table 4. (PA) is on the impact (x ± s, n=8) of rat body weight

** P<0.01, compares with the blank Vehicle controls group same period; #P<0.05, compares with the 2.0%NaCl model control group same period

Oligomeric potassium alginate is milky or yellow particle sprills, has hygroscopicity, and its solution viscosity is low, be suitable for being developed to Cardia Salt for health care, oligomeric potassium alginate is sour for raw material with brown algae extract Medicinal Algae, through degraded salify, and the sylvite of the alginic acid of obtained low polymerization degree.

China's Chinese Traditional Medicine thinks that sea-tangle has vanishing sputum and dispelling knot, effect of inducing diuresis for removing edema.Oligomeric potassium alginate extracts from Phaeophyta plant sea-tangle and obtains through degradation technique preparation.Result of study shows: gastric infusion is after 21 days and 28 days continuously, 100,250 or the oligomeric potassium alginate of 500mg/kg all can reduce spontaneous hypertensive rat SHRs blood pressure level very significantly, its action intensity is similar to 6.5mg/kg Hydrochioro (being equivalent to 3 ~ 12 times of clinical equivalent amount).Drug withdrawal is after 3 days, and the hypotensive effect of Hydrochioro disappears; But when drug withdrawal 3 days, high, medium and low three dosage of oligomeric potassium alginate all had remarkable hypotensive effect; During drug withdrawal 6 days, 250 and the oligomeric potassium alginate of 500mg/kg still there is the hypotensive effect of highly significant.We further radiate pharmacokinetics result of study display: the half-life after oligomeric potassium alginate oral administration in Mice Body is 36.28 hours, after pointing out oligomeric potassium alginate drug withdrawal continue hypotensive effect may with eliminate in its body slowly relevant.

The potassium of human body is mainly from food, and major part is absorbed rapidly by small intestine.Potassium accounts for 5% of human body inorganic salts, is the nutrient of needed by human.Clinical research shows, in Essential Hypertensive Patients urine, potassium discharge rate is lower than normal person, and appropriate benefit potassium is to mild hypertension and there is some normotensive subjects of hypertension factor to have hypotensive effect, and this may be relevant with the regulating action of potassium to water and isohydria.Results of animal also shows: appropriate benefit potassium can reduce the blood pressure level of hypertension animal.

In sum, derive from the oligomeric potassium alginate of natural algae plant, molecular weight is little, be beneficial to absorption, have highly significant and lasting hypotensive effect to SHRs, the mechanism of its hypotensive effect may with low ALG itself or low molecule alginic acid and potassium ion interact (such as low ALG affects the pharmaco-kinetic properties in potassium ion body) relevant.Experiment in vitro is pointed out: oligomeric potassium alginate PA has the diastole effect of that dosage is correlated with, non-endothelium-dependent relaxation to myocardium vessel smooth muscle, and its mechanism may be relevant with suppression VSMC voltage-dependent ca channel.

Oligomeric potassium alginate sample is pressed body weight 60Kg and is calculated, and takes 1 day, each 2.8 grams, and secondary buck effect can reach national health food required standard completely.The antihypertensive effect half-life longer (144 hours can be reached).

Embodiment 6, preparation containing oligomeric potassium alginate Cardia Salt

In the present embodiment, oligomeric potassium alginate is prepared according to the method for embodiment 1; Marine alga oligopeptide is prepared according to the method for embodiment 2

Cardia Salt in the present embodiment is made up of following component: NaCl 550g,

Oligomeric potassium alginate 160g, marine alga oligopeptide 60g, butanedioic acid 2.9g.

In mortar, pulverize commercially available (pure quality) NaCl and butanedioic acid, and sieve in 90 tm screen.550 grams of NaCl (d50 is 59 microns) are got from through the fraction of sieve, 2.9 grams of butanedioic acids (d50 is 58 microns), with 160 grams of oligomeric potassium alginates (d50 is 58 microns), oligomeric potassium alginate sprays presses dry weight basis 60 grams of marine alga oligopeptide solution, fully mixes.On Herzog tablet press machine, 1.0t/cm2 pressure (being equivalent to the pressure of 100MPa) is used to manufacture 50 grams of pellet (40 mm dias, 20 height) by this mixture.Resulting pellet is diametrically broken, and on Frewitt screen mill, use the sieve grinding of 6 millimeters, 3 millimeters and last 1 millimeter.Use the sieve of 710,500,280 and 90 microns that the product from this Frewitt screen mill is sieved into fraction.Further analysis fraction 280 to 710 microns (namely merge two fractions) also determines the Cardia Salt of the d50 with 396 microns.

Embodiment 7, preparation containing oligomeric potassium alginate Cardia Salt

In the present embodiment, oligomeric potassium alginate is prepared according to the method for embodiment 1; Marine alga oligopeptide is prepared according to the method for embodiment 2.

The Cardia Salt of this embodiment contains the NaCl of 71.5% (weight), the oligomeric potassium alginate of 22% (weight), marine alga oligopeptide and 0.5% (weight) yeast hydrolyate (ribonucleotide) of 6% (weight).

The Alpine 160UPZ needle mill run with 500rpm grinds NaCl.The NaCl ground (d50=69 μm) is loaded in 2 liters of Nautamixer with 1.5 kilograms of batches together with the potassium alginate do not ground and marine alga oligopeptide (d50=58 μm), and in 19rpm mixing at least 10 minutes.Mixed-powder is collected in feed bin, therefrom manually supplies Herzog tablet press machine with 50 grams of shares.Applied pressure is 0.5t/cm ²to 1.0t/cm ²(being equivalent to the pressure of 50 to IOOMPa).Most of pellet is at 1.0t/cm ²pressure system.Most of pellet is of a size of 40 mm dias and ~ 20 height.Resulting pellet is diametrically broken.

After fragmentation in advance, diameter 200 millimeters, roll spacing 3.0 millimeters, roller speed 195 and the Merz smooth roll pulverizer of 300rpm is adopted to carry out the further pulverizing of pellet.Milling product (now with 0.8 millimeter roll spacing run) again on Merz smooth roll pulverizer.The product of pulverizing is sieved on the Mogensen Piccolo being furnished with 200 microns and 710 tm screen.Further analysis fraction 200 to 710 microns also determines the Cardia Salt of the d50 with 455 microns.

Embodiment 8, preparation containing oligomeric potassium alginate Cardia Salt

In the present embodiment, oligomeric potassium alginate is prepared according to the method for embodiment 1; The preparation method of shellfish oligopeptide is as described below:

Papain, to the enzymolysis of shellfish protein, gets dried scallop fresh goods 10 kilograms, and homogeneous becomes to stick with paste, and temperature rises to 50 DEG C by 40 DEG C, and ammonia nitrogen stripping increases obviously.When temperature raises further, increase not obvious and have a declining tendency with temperature increase.This is because suitably heat, protein structure is loosened, exposes more enzyme action site, enzymatic activity also reaches the best use of state simultaneously, reduces gradually, cause amino nitrogen content also to reduce along with temperature continues to raise enzymatic activity.Therefore, we select 50 DEG C for the best use of temperature of hydrolysis.The maximum reaction temperature of enzyme is 60 DEG C, and under this temperature conditions, the enzyme of 70% that still keeps of temperature bath 100min is lived.Enzymolysis pH affects hydrolysising condition to enzyme digestion reaction: enzyme dosage 2.5%, solid-to-liquid ratio 1:3, time 6h, hydrolysis temperature 50 DEG C.Learn according to interrelated data, the optimum pH of papain, about 6.7, therefore, have chosen 6.25,6.5,6.75,7,7.255 levels.The enzymolysis result of papain to dried scallop shows that the optimal reaction pH value of enzyme is 7.6, has good adaptability under the alkali condition of pH 9.0.The dried scallop homogeneous separation solution of 2.0-2.5% is after papain hydrolysis, and the free aminoacid contents such as serine, threonine, proline, histidine, methionine obviously increase, and the every 100ml of dried scallop polypeptide improves 92-98mg.

The optimum hydrolysis technique of papain hydrolysis.Single factor experiment shows to be about 5h at enzymolysis time, concentration of substrate is 4%, enzyme concentration is about 5500U/g, pH value is in 7.0 ~ 7.5 scopes, and when temperature is 50 DEG C, papain hydrolysis effect is better.Orthogonal test shows, the impact order of 3 factors is: enzyme concentration > concentration of substrate > hydrolysis time; Optimum hydrolysis technique is: hydrolyzate pH value 7.5, and enzyme concentration is 5500U/g, and concentration of substrate is 4%, temperature 50 C, hydrolysis 6h, and degree of hydrolysis can reach 37.25% employing papain and is hydrolyzed and can obtains the enzymolysis liquid of higher degree of hydrolysis with this understanding.

Cardia Salt in the present embodiment is made up of following component: NaCl 500g,

Oligomeric potassium alginate 126g, shellfish oligopeptide 45g, butanedioic acid 2.9g.

Concrete preparation method is as described below:

Get pure quality NaCl (500 grams, d50 is 375 microns), oligomeric potassium alginate (126 grams, d50 is 296 microns), butanedioic acid (2.9 grams, d50 is 464 microns) and shellfish oligopeptide (45 grams, d50 is 58 microns) fully mix.On Herzog tablet press machine, 50 grams of pellet (40 mm dias, 20 height) are manufactured by this mixture.Applied pressure is 1.0t/cm2 pressure (being equivalent to the pressure of 100MPa).Resulting pellet is diametrically broken, and on Frewitt screen mill, use the sieve grinding of 6 millimeters, 3 millimeters and last 1 millimeter.Use the sieve of 710,500,280 and 90 microns that the product from this Frewitt screen mill is sieved into fraction.Check lower than 90 microns, 90 to 280 microns (d50 is 231 microns), 280 to 500 microns (d50 is 381 microns), 500 to 710 microns (d50 is 587 microns) and the fraction higher than 710 microns.Further analysis fraction 90 to 710 microns also determines the Cardia Salt of the d50 with 445 microns.

Embodiment 9, preparation containing oligomeric potassium alginate Cardia Salt

In the present embodiment, oligomeric potassium alginate is prepared according to the method for embodiment 1; The preparation method of maize oligopeptide is as described below:

Papain, to the enzymolysis of zein, gets corn protein powder 2 kilograms, adds 3 premium on currency soaked overnight, after gelatinization, zein is stuck with paste temperature and rises to 50 DEG C by 40 DEG C, and ammonia nitrogen stripping increases obviously.When temperature raises further, increase not obvious and have a declining tendency with temperature increase.This is because suitably heat, protein structure is loosened, exposes more enzyme action site, enzymatic activity also reaches the best use of state simultaneously, reduces gradually, cause amino nitrogen content also to reduce along with temperature continues to raise enzymatic activity.Therefore, we select 50 DEG C for the best use of temperature of hydrolysis.The maximum reaction temperature of enzyme is 60 DEG C, and under this temperature conditions, the enzyme of 70% that still keeps of temperature bath 100min is lived.Enzymolysis pH affects hydrolysising condition to enzyme digestion reaction: enzyme dosage 2.5%, solid-to-liquid ratio 1:3, time 6h, hydrolysis temperature 50 DEG C.Learn according to interrelated data, the optimum pH of papain, about 6.7, therefore, have chosen 6.25,6.5,6.75,7,7.255 levels.The enzymolysis result of papain to zein shows that the optimal reaction pH value of enzyme is 7.8, has good adaptability under the alkali condition of pH 9.0.25% homogenised paste is after papain hydrolysis, and the free aminoacid contents such as serine, threonine, proline, histidine, methionine obviously increase, and the every 100ml of Semen Maydis polypeptide improves 94-98mg.

The optimum hydrolysis technique of papain hydrolysis.Single factor experiment shows to be about 5h at enzymolysis time, concentration of substrate is 4%, enzyme concentration is about 5500U/g, pH value is in 7.0 ~ 7.5 scopes, and when temperature is 50 DEG C, papain hydrolysis effect is better.Orthogonal test shows, the impact order of 3 factors is: enzyme concentration > concentration of substrate > hydrolysis time; Optimum hydrolysis technique is: hydrolyzate pH value 7.8, and enzyme concentration is 5500U/g, and concentration of substrate is 4%, temperature 50 C, hydrolysis 6h, and degree of hydrolysis can reach 37.45% employing papain and is hydrolyzed and can obtains the enzymolysis liquid of higher degree of hydrolysis with this understanding.

The Cardia Salt of this embodiment contains 72% (weight) NaCl and contains 20% (weight) oligomeric potassium alginate and 7.5% (weight) maize oligopeptide, also containing 0.3% (weight) yeast extract (ribonucleotide) and 0.2% (weight) alginic acid magnesium.

Commercially available NaCl (d50=375 μm) and homemade oligomeric potassium alginate (d50=296 μm) is used to manufacture this Cardia Salt.Be feed these components and d50 together with the maize oligopeptide do not ground of 86 microns and yeast extract (ribonucleotide) alginic acid magnesium and mix.On Herzog tablet press machine, 1.0t/cm2 pressure (being equivalent to the pressure of IOO MPa) is used to manufacture 50 grams of pellet (40 mm dias, 20 height) by this mixture.Resulting pellet is diametrically broken, and on Frewitt screen mill, use the sieve grinding of 6 millimeters, 3 millimeters and last 1 millimeter.AG divides the component of the particle obtaining 90-200 micron and 200-710 micron to distribute, 90 to 710 microns and determine the d50 with 435 microns.

Embodiment 10, preparation containing oligomeric potassium alginate Cardia Salt

Cardia Salt in the present embodiment is made up of the component of following percent mass: NaCl 74.7%, oligomeric potassium alginate 18.4%, marine alga oligopeptide 6.7%, alginic acid magnesium 0.2%.

By 160 grams of oligomeric potassium alginates (d50 is 258 microns); spray marine alga oligopeptide solution 120ml (by dry weight basis 58.26 grams) to mix afterwards; add 650 grams of NaCl (d50 is 39 microns) and 1.74g alginic acid magnesium; granulation on comminutor; cross 280 tm screen; be 785 grams after obtaining the Cardia Salt drying containing oligomeric potassium alginate and marine alga oligopeptide, analyze fraction 280 to 710 microns (namely merging two fractions) further and also determine the d50 with 598 microns.Be left behind NaCl and contain the Cardia Salt sample of oligomeric potassium alginate and marine alga oligopeptide for preparation next time.

Embodiment 11, preparation containing oligomeric potassium alginate Cardia Salt

In the present embodiment, oligomeric potassium alginate is prepared according to the method for embodiment 1; Shellfish oligopeptide is prepared according to the method for embodiment 8.

160 grams of oligomeric potassium alginates (d50 is 258 microns) are sprayed shellfish oligopeptide solution 120ml (by dry weight basis 58.26 grams) mixing; add 650 grams of NaCl (d50 is 39 microns)) and 1.74g alginic acid magnesium; granulation on comminutor; on Herzog tablet press machine, 1.0t/cm2 pressure (being equivalent to the pressure of 1OO MPa) is used to manufacture 50 grams of pellet (40 mm dias, 20 height) by this mixture.Resulting pellet is diametrically broken, and on Frewitt screen mill, use the sieve grinding of 6 millimeters, 3 millimeters and last 1 millimeter.Use the sieve of 710,500,280 and 90 microns that the product from this Frewitt screen mill is sieved into fraction.Further analysis fraction 280 to 710 microns (namely merge two fractions) also determines the Cardia Salt of the d50 with 498 microns.

Embodiment 12, preparation containing oligomeric potassium alginate Cardia Salt

In the present embodiment, oligomeric potassium alginate is prepared according to the method for embodiment 1; Maize oligopeptide is prepared according to the method for embodiment 9

The Cardia Salt of this embodiment contains 72% (weight) NaCl, 20.5% (weight) oligomeric potassium alginate and 7% (weight) maize oligopeptide, 0.5% (weight) yeast extract (ribonucleotide).

Commercially available NaCl (d50=375 μm) and homemade oligomeric potassium alginate (d50=296 μm) is used to manufacture this formulation.Be feed these components and d50 together with the maize oligopeptide do not ground of 86 microns and yeast extract and mix.On Herzog tablet press machine, 1.0t/cm is used by this mixture ²pressure (being equivalent to the pressure of IOO MPa) manufactures 50 grams of pellet (40 mm dias, 20 height).Resulting pellet is diametrically broken, and on Frewitt screen mill, use the sieve grinding of 6 millimeters, 3 millimeters and last 1 millimeter.AG divides the component of the particle obtaining 90-200 micron and 200-710 micron to distribute, 90 to 710 microns and determine the Cardia Salt of the d50 with 438 microns.

Embodiment 13, preparation containing oligomeric potassium alginate Cardia Salt

100 grams of oligomeric potassium alginates (d50 is 258 microns) are sprayed marine alga oligopeptide solution 120ml (by dry weight basis 48.75 grams) mixing; add 500 grams of NaCl (d50 is 39 microns _) and 2.25g alginic acid magnesium; granulation on comminutor, uses 1.0t/cm by this mixture on Herzog tablet press machine ²pressure (being equivalent to the pressure of 1OO MPa) manufactures 50 grams of pellet (40 mm dias, 20 height).Resulting pellet is diametrically broken, and on Frewitt screen mill, use the sieve grinding of 6 millimeters, 3 millimeters and last 1 millimeter.Use the sieve of 710,500,280 and 90 microns that the product from this Frewitt screen mill is sieved into fraction.Further analysis fraction 280 to 710 microns (namely merge two fractions) also determines the Cardia Salt of the d50 with 498 microns.

Embodiment 14, preparation containing oligomeric potassium alginate Cardia Salt

171.76 grams of oligomeric potassium alginates (d50 is 258 microns) are sprayed marine alga oligopeptide solution 120ml (by dry weight basis 54.59 grams) mixing; add 501.46 grams of NaCl (d50 is 39 microns _) (wherein containing 1.46g alginic acid magnesium); granulation on comminutor, uses 1.0t/cm by this mixture on Herzog tablet press machine ²pressure (being equivalent to the pressure of 1OO MPa) manufactures 50 grams of pellet (40 mm dias, 20 height).Resulting pellet is diametrically broken, and on Frewitt screen mill, use the sieve grinding of 6 millimeters, 3 millimeters and last 1 millimeter.Use the sieve of 710,500,280 and 90 microns that the product from this Frewitt screen mill is sieved into fraction.Further analysis fraction 280 to 710 microns (namely merge two fractions) also determines the Cardia Salt of the d50 with 498 microns.

Embodiment 15. is containing the fluidized drying processing method of potassium alginate Cardia Salt

In the present embodiment, Cardia Salt contains 72% (weight) NaCl, 20.5% (weight) oligomeric potassium alginate and 7% (weight) marine alga oligopeptide, 0.4% (weight) yeast extract (ribonucleotide) and 0.1% calcium zinc-magnesium mineral matter.

A. spray potassium alginate in the end is for the functional alginate dressing of sodium chloride particulate.

End spray apparatus is made up of a conical material trough and built-in cylindrical spacer, and the deflector of different-diameter distribution hole is housed bottom material trough, with the stream condition inside and outside space ring.In spacer ring, air-flow is maximum, and material moves upward at a high speed in spacer ring, falls into outside spacer ring after entering propagation chamber, and the outer material of spacer ring flows in spacer ring automatically, so circulates.Liquid feeding atomizer mounting guiding board center, the bottom-up hydrojet of nozzle, direction and sodium chloride fine, airflow direction are consistent.

B. top spray is used for the functional alginate layering pelletization of potassium alginate drying, sodium chloride particulate.

Top spray device is made up of the material trough of a taper and propagation chamber.Because material trough is taper, ensure that the fountain type fluidized state in material trough, material in inlet air air propels hopper upwards enters propagation chamber, because propagation chamber's diameter is greater than material trough, inlet air flow velocity declines, material is because declining when self gravitation is greater than wind-force, and sodium chloride fine is back and forth movement in hopper and propagation chamber.There is multiple nozzle installing port at propagation chamber top, be used in granulation and coating process and spray into atomized liquid.

Fluidized drying technical study

Potassium alginate marine alga peptide combinations concentration counts 20% with dry weight, it is 40 ~ 60 DEG C, 60 ~ 80 DEG C, 80 ~ 100 DEG C by the temperature of charge containing prepared by yeast hydrolysate and calcium zinc-magnesium mineral matter in potassium alginate marine alga peptide combinations, hydrojet speed 20 ~ 25 ls/h, 25 ~ 35 ls/h, 35 ~ 40 ls/h screen, result: when potassium alginate marine alga peptide combinations temperature of charge is 40 ~ 60 DEG C, temperature of charge is too low, powder is not easily dry, easily lumps.Hydrojet speed is 20 ~ 25 ls/h, and hydrojet speed is low, and flow is little, affects efficiency.Hydrojet speed is 35 ~ 40 ls/h, and hydrojet speed is fast, and powder is not easily completely dry, easily lumps.When temperature of charge is 80 ~ 100 DEG C, temperature of charge is too high, may cause the decomposition of active ingredient in composition intermediates.Therefore select alginate temperature of charge to be 60 ~ 80 DEG C, concentration 20%, sodium chloride fine 12-25 kilogram that hydrojet speed 25 ~ 35 ls/h is less than 600 microns for diameter carries out functional potassium alginate (sodium) layering pelletization by fluidized drying condition to sodium chloride fine.Fluidized drying condition have employed end spray potassium alginate marine alga peptide combinations liquid respectively, top spray is used for potassium alginate marine alga peptide combinations liquid all can obtain the particle that the good d50 containing oligomeric potassium alginate marine alga peptide of quality is 630 microns, continue the pastel adding flavor enhancement and mineral matter, stir dry Cardia Salt sample.

Embodiment 16, the blood pressure lowering effect containing potassium alginate Cardia Salt of the present invention are tested

That one, is prepared by embodiment 6-15 carries out blood pressure lowering effect test respectively containing oligomeric potassium alginate Cardia Salt, and concrete grammar is as described below:

Tail pulses method of indirectly measuring blood pressure is adopted to measure SHRs systolic pressure, 40 rats are divided into 4 groups at random, often organize 10: blank Vehicle controls group, potassium alginate Cardia Salt are in potassium alginate high dose, middle dosage and low dose group (500,250,100mg/kg), every day gastric infusion, successive administration 28d; Measure blood pressure weekly, and the blood pressure of 3d, 6d after observing drug withdrawal.The SHRs blood pressure level of successive administration 21d and low molecule potassium alginate 3 dosage groups all reduces (P0.01); During drug withdrawal 3d and 6d, when drug withdrawal 3d, the systolic pressure of high, medium and low 3 the dosage groups of potassium alginate Cardia Salt is all lower than the Vehicle controls group same period (P0.05 or P0.01); During drug withdrawal 6d, 250 and 500mg/kg potassium alginate Cardia Salt still can reduce SHRs blood pressure level (P0.01).The administration of conclusion potassium alginate Cardia Salt continuous oral can dose-dependently reduce SHRs blood pressure, and drug withdrawal 6d still presents lasting hypotensive effect, this may with eliminate in body after potassium alginate Cardia Salt oral administration slowly relevant.Blood pressure lowering effect result of the test is as shown in table 9.

Table 9. potassium alginate Cardia Salt (in potassium alginate) is on the impact (mmHg) of SHR rat blood pressure

Two, potassium alginate Cardia Salt ingestion experiment

Test crowd, select spontaneous hypertension patient, test crowd often organizes 30 people, ingest containing 35% potassium chloride Cardia Salt for control group, ingest every day containing 35% potassium chloride Cardia Salt 9.0 grams, wherein 5.9 grams, sodium chloride, 3.1 grams, potassium chloride. ingest containing oligomeric potassium alginate Cardia Salt for test group, ingest every day containing oligomeric potassium alginate Cardia Salt 9.0 grams (respectively the method for embodiment 6-15 prepare containing oligomeric potassium alginate Cardia Salt).Ingest one month, every day all carries out test record to the systolic pressure of every ingester and diastolic pressure. and observed result lists following table 11-14 in.

Table 11. ordinary circumstance compares

The change of table 12. systolic pressure is compared (mmHg, )

The change of table 13. diastolic pressure is compared (mmHg, )

Table 14. antihypertensive effect compares

Grouping	Reciprocal	Effective	Effectively	Invalid	Total effective rate (%)
						Embodiment 6	30	10	15	5	83.33
Embodiment 7	30	11	14	5	83.33
						Embodiment 8	30	12	13	5	83.33
Embodiment 9	30	15	10	5	83.33
						Embodiment 10	30	13	12	5	83.33
Embodiment 11	30	12	13	5	83.33
						Embodiment 12	30	11	14	5	83.33
Embodiment 13	30	9	16	5	83.33
						Embodiment 14	30	13	12	5	83.33

Embodiment 15	30	12	13	5	83.33
						Control group	30	3	4	23	22.33**

The above results shows, in the hyperpietic ingested containing 35% potassium chloride Cardia Salt, belong to hypovolemic and hypertensively show certain effect, the total effective rate of the hyperpietic containing oligomeric potassium alginate Cardia Salt of the present invention that ingests is far away higher than the hyperpietic's (control group) ingested containing 35% potassium chloride Cardia Salt.Further, experiment proves, ingests containing oligomeric potassium alginate Cardia Salt secondary buck effect a little more than oligomeric sodium alginate Cardia Salt of ingesting, and prompting potassium ion demonstrates effective secondary buck effect.

Claims

1. an oligomeric potassium alginate, its weight average molecular weight is 700 dalton-10,000 dalton, and in described alginic acid, the molar ratio of mannuronic acid unit and guluronic acid units is 0.3-3.3, and Ubbelohde viscosity is 3-16.

2. oligomeric potassium alginate according to claim 1, is characterized in that: its weight average molecular weight is 1,000-4,500 dalton; And the molar ratio of mannuronic acid unit and guluronic acid units is 0.4-3.3 in described alginic acid.

3. the application of the oligomeric potassium alginate described in claim 1 or 2 in the health food preparing secondary buck or Cardia Salt product.

4., containing a Cardia Salt for potassium alginate, comprise the oligomeric potassium alginate described in claim 1 or 2 and sodium chloride.

5. Cardia Salt according to claim 4, is characterized in that: the weight ratio of described sodium chloride and oligomeric potassium alginate is (48-83): (13-40).

6. the Cardia Salt according to claim 4 or 5, is characterized in that: also comprise oligopeptide in described Cardia Salt.

7. Cardia Salt according to claim 6, is characterized in that: described oligopeptide is marine alga oligopeptide, maize oligopeptide or shellfish oligopeptide.

8. Cardia Salt according to claim 6, is characterized in that: the mass ratio of described sodium chloride, oligomeric potassium alginate and oligopeptide is (48-83): (13-40): (3.8-11.5).

9. according to the Cardia Salt in claim 4-8 described in any one, it is characterized in that: in described Cardia Salt, also comprise additive, described additive is selected from taste improving compounds, taste masked agent, mineral matter, anti-caking agent or flowing additive, one or more any combination in taste improving compounds, taste masked agent, mineral matter, anti-caking agent and flowing additive; Described sodium chloride, oligomeric potassium alginate, oligopeptide and additive weight ratio are (48-83): (13-40): (3.8-11.5): (0.2-0.5).

10. Cardia Salt according to claim 9, is characterized in that: described additive accounts for the 0.2%-0.5% containing alginate Cardia Salt gross weight.

11. Cardia Salts according to claim 9, is characterized in that: described taste masked agent is selected from following substances: edible organic acid; Amino acid and derivative thereof; Yeast; Yeast extract; From the protein hydrolysate in yeast extract and so on source; Peptide; Hydrolyzed vegetable protein; Hydrolyzed fat; Ribonucleotide; Flavonoids; The acid amides of amino acid and dicarboxylic acids; One in trehalose and gluconate or two or more any combination; Or their combination;

12. Cardia Salt according to claim 9, is characterized in that: described Cardia Salt is the particle of the particle diameter with 250 microns to 1 millimeter.

13. Cardia Salts according to claim 12, is characterized in that: the preparation method of described Cardia Salt pulverizes the Cardia Salt particle obtaining the particle diameter with 250 microns to 1 millimeter after comprising the salt granulating powders using the oligomeric potassium alginate being greater than 150 microns to stick below 50 micron granularities or the pressure compacting re-using 40 to 100MPa.

The preparation method of 14. 1 kinds of Cardia Salts; comprise the steps: according to constituent mass ratio according to claim 5, it is that to stick granularity be the Cardia Salt particle that the rear pulverizing of pressure compacting that the sodium chloride powder granulation of less than 50 microns re-uses 40 to 100MPa obtains the granularity with 250 microns to 1 millimeter for the sodium chloride powder granulation of less than 50 microns or the oligomeric potassium alginate that uses granularity to be greater than 150 microns that the oligomeric potassium alginate using granularity to be greater than 150 microns sticks granularity.

The preparation method of 15. 1 kinds of Cardia Salts, comprise the steps: according to component ratio described in claim 8, be spray oligopeptide solution in the oligomeric alginate powder of 258-270 micron at d50, the NaCl powder that d50 is 39-50 micron is added after mixing, granulation on comminutor, drying, uses the sieve of 280 microns, and sieve the Cardia Salt obtained containing oligomeric potassium alginate and oligopeptide. and determine to have the d50 of 498-640 micron; Be left behind NaCl and contain the Cardia Salt sample of oligomeric potassium alginate and oligopeptide for preparation next time.

The preparation method of 16. 1 kinds of Cardia Salts, comprise the steps: according to component ratio described in claim 8, mix after d50 is spray oligopeptide solution in the oligomeric potassium alginate powder of 258-270 micron, add the NaCl powder that d50 is 39-50 micron, granulation on comminutor, uses the pressure of 40 to 100MPa to manufacture pellet on Herzog tablet press machine by the mixture obtained; Then resulting pellet is diametrically broken, and the Cardia Salt particle of the d50 with 398-520 micron is obtained in screen mill grinding screening.

The preparation method of 17. 1 kinds of Cardia Salts, comprise the steps: according to ratio of weight and number according to claim 9, oligomeric alginate and oligopeptide and all the other components except sodium chloride are mixed with into dry weight and count the oligomeric alginate of 20% and the composition solution of oligopeptide, it is 60 ~ 80 DEG C according to the composition solution temperature of oligomeric alginate and oligopeptide, hydrojet speed 25 ~ 35 ls/h, it is 630 microns of Cardia Salt samples that sodium chloride fine 12-25 kilogram being less than 600 microns for diameter carries out to sodium chloride fine the d50 that dressing obtains containing oligomeric alginate and oligopeptide by fluidized drying, described fluidized drying condition adopts the end to spray the composition solution of oligomeric alginate and oligopeptide or the top spray composition solution for oligomeric alginate and oligopeptide.

18. the application of oligomeric potassium alginate described in claim 1-2 in the product preparing prevention or assisting in treating hypertension.

19. application according to claim 18, is characterized in that: described oligomeric potassium alginate daily intake is 2.8 grams/60kg.

20. the application of the Cardia Salt of claim in 4-13 described in any one in the product preparing prevention or assisting in treating hypertension.