WO2016045309A1 - 新型低钠盐的组成、制备和用途 - Google Patents

新型低钠盐的组成、制备和用途 Download PDF

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WO2016045309A1
WO2016045309A1 PCT/CN2015/073094 CN2015073094W WO2016045309A1 WO 2016045309 A1 WO2016045309 A1 WO 2016045309A1 CN 2015073094 W CN2015073094 W CN 2015073094W WO 2016045309 A1 WO2016045309 A1 WO 2016045309A1
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alginate
sodium salt
oligomeric
potassium
oligopeptide
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PCT/CN2015/073094
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English (en)
French (fr)
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于传兴
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大连雅威特生物技术股份有限公司
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Publication of WO2016045309A1 publication Critical patent/WO2016045309A1/zh

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • This application relates to low sodium salts containing oligomeric potassium alginate and their preparation and use.
  • the main component of salt is sodium chloride.
  • Sodium chloride exists in the form of sodium ions and chloride ions in the human body. Excessive intake of sodium chloride can induce high blood pressure, leading to coronary heart disease, cerebral infarction, renal dysfunction, retinopathy and other diseases, seriously affecting the quality of life and even life. According to the survey of the 35-74 year old adult population in China, the prevalence of hypertension is 27.2%. The awareness, treatment and control of hypertension in China is worrying: in existing patients, less than 45% of patients diagnosed with disease, not more than 30% of those taking antihypertensive drugs, and less than 10% of people have stable blood pressure. control.
  • Essential hypertension is one of the most common diseases that threaten human health, and its pathogenesis has not yet been fully elucidated. Studies have shown that the pathogenesis of essential hypertension is related to the decompensation of blood pressure regulation mechanism caused by individual genetic background and various acquired environmental factors, including the activation of renin-angiotensin system (RAS) and high sodium. Intake, insulin resistance and psychosis.
  • RAS renin-angiotensin system
  • hypertension includes both non-pharmacological and medical treatment.
  • antihypertensive drugs diuretics, alpha blood blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and angiotensin II.
  • ACE angiotensin-converting enzyme
  • Receptor antagonist The efficacy and adverse reactions of antihypertensive drugs vary widely from individual to individual.
  • Non-pharmacological interventions mainly regulate blood pressure by restricting the intake of salt, rational diet, weight loss, exercise, etc., and reduce the cardiovascular complications of hypertension to a certain extent.
  • the low sodium salt is based on iodized salt, and a certain amount of potassium chloride and magnesium sulfate are added to improve the balance of sodium (Na + ), potassium (K + ) and magnesium (Mg 2+ ) in the body. To prevent high blood pressure.
  • Some manufacturers now produce low sodium salts in an effort to reduce sodium chloride intake.
  • the sodium chloride is low in the low sodium salt, and potassium chloride is added.
  • Some low sodium salts contain up to 20g/100g-35g/100g of potassium chloride.
  • Alginate has been used in pharmaceutical preparations. Potassium alginate (C 6 H 7 O 8 K) n is mainly composed of the potassium salt of alginic acid.
  • Alginic acid is a copolymer composed of ⁇ - ⁇ -alginic acid mannuronic acid (M unit) and ⁇ - ⁇ -aldalduronic acid (G unit) linked by 1,4-glycosidic bond and composed of different GGGMMM fragments.
  • M unit ⁇ - ⁇ -alginic acid mannuronic acid
  • G unit ⁇ - ⁇ -aldalduronic acid linked by 1,4-glycosidic bond and composed of different GGGMMM fragments.
  • the concentration of G and M acid (G:M ratio) determines properties such as different structures and biocompatibility.
  • Alginic acid (such as brown algae) found in nature has a molar ratio of G to M of 0.2 to 2.5 and a molecular weight of 100,000 Daltons to 1,500,000 Daltons.
  • US 2009/0104330 discloses a low sodium salty composition for reducing sodium chloride in food products.
  • the composition contains at least one of sodium chloride, a food acid and a food acid salt, an amino acid and an amino acid salt At least one of them may additionally contain potassium chloride, yeast extract, sweeteners and flavors.
  • the composition is said to have a reduced metallic/bitter taste, enhanced salty character and enhanced salty taste.
  • compositions made as in US 2009/0104330 are easily separated as explained above, for example during transport and storage, which results in a product having a composition different from what is expected, which in turn affects the function of the composition.
  • the low sodium salt provided by the present application comprises sodium chloride and potassium oligomeric potassium alginate, wherein the oligomeric potassium alginate has a weight average molecular weight of 700 Daltons to 10,000 Daltons and a Ubbel viscosity of 3-16. And the molar ratio of the mannuronic acid unit to the guluronic acid unit in the oligomeric potassium alginate is from 0.3 to 3.3.
  • the oligomeric alginic acid in the oligomeric potassium alginate of the present application has a weight average molecular weight of 1,000 Daltons to 4,500 Daltons, and the mannuronic acid unit and the ancient oligomeric alginic acid
  • the molar ratio of the saccharuronic acid unit is from 0.4 to 3.3.
  • the raw material commonly used to prepare the above oligomeric alginic acid is brown algae.
  • Various brown algae can be used as raw materials for the production of alginic acid, such as kelp, water cloud, algae, carrageen, and sargasso.
  • kelp kelp
  • kelp kelp
  • macroalgae kelp
  • sargasso such as S. cerevisiae, S. cerevisiae.
  • the method of preparing the above oligomeric alginic acid provided by the present application includes a conventional degradation step.
  • the method comprises degrading alginic acid having a weight average molecular weight of from 10,000 Daltons to 1,500,000 Daltons, the degradation step comprising a physical degradation step, a photochemical degradation step, and immobilized enzyme degradation
  • the degradation step comprising a physical degradation step, a photochemical degradation step, and immobilized enzyme degradation
  • the physical degradation step, the photochemical degradation step, the immobilized enzyme degradation step, and the oxidative degradation step are performed prior to the degradation step.
  • the physical degradation step, the photochemical degradation step, the immobilized enzyme degradation step, and the oxidative degradation step are well known in the art and are described in detail in PCT/CN99/00202, the entire disclosure of which is incorporated herein by reference.
  • the physical steps include ultrasonic treatment or high-speed shear treatment;
  • the photochemical step is treatment using optical radiation and catalysis;
  • the oxidative degradation step includes using an organic oxidant and/or an inorganic oxidant such as hydrogen peroxide, peracetic acid, potassium peroxide, or Oxidized potassium carbonate, potassium perborate (sodium), potassium permanganate, ammonium persulfate, potassium persulfate double salt, potassium chlorite, sodium chlorite, etc.
  • immobilized enzyme degradation step includes immobilization of algae using a porous sodium glass ball carrier After the acid decomposing enzyme, the column is decomposed.
  • the oligomeric potassium alginate is obtained by neutralizing the above oligomeric alginic acid with an alkaline potassium ion.
  • the oligomeric sodium alginate is obtained by neutralizing the above oligomeric alginic acid with a basic sodium ion.
  • the application provides a low sodium salt comprising potassium alginate, including the oligomeric potassium alginate and sodium chloride.
  • the weight ratio of the sodium chloride to the oligomeric potassium alginate is (48-83): (13-40).
  • the low sodium salt further includes an oligopeptide.
  • the oligopeptide is an algae oligopeptide, a corn oligopeptide or a shellfish oligopeptide.
  • the mass ratio of the sodium chloride, the oligomeric potassium alginate and the oligopeptide is (48-83): (13-40): (3.8-11.5).
  • the low sodium salt further includes an additive selected from the group consisting of a taste improver, a taste masking agent, a mineral, an anti-caking agent or a flow additive, a taste improver, a taste masking agent, a mineral, an anti-caking agent, and One or a combination of two or more of the flow additives; the weight ratio of the sodium chloride, the oligomeric potassium alginate, the oligopeptide, and the additive is (48-83): (13-40): (3.8-11.5) : (0.2-0.5).
  • the additive comprises from 0.2% to 0.5% by weight based on the total weight of the alginate low sodium salt.
  • the taste masking agent is selected from the group consisting of: an edible organic acid; an amino acid and a derivative thereof; a yeast; a yeast extract; a hydrolyzed protein derived from a source such as yeast extract; a peptide; a hydrolyzed vegetable protein; a hydrolyzed fat; a ribonucleoside An acid; a flavonoid; an amide of an amino acid and a dicarboxylic acid; one or a combination of two or more of trehalose and gluconate; or a combination thereof;
  • the taste improving agent is selected from one or a combination of two or more of the following: derived from allspice, basil, pepper, cinnamon, clove, cumin, dill, garlic, marjoram, nutmeg, red pepper , oily resin and oil of any of black pepper, rosemary and turmeric; essential oil; citrus oil; garlic flavor; plant extract; protein hydrolysate; natural and artificial mixed flavor, and by reducing sugar and A processed fragrance prepared by a Maillard reaction between protein-derived components; the mineral (trace element) calcium, magnesium, zinc, chromium, iron, molybdenum, copper, manganese is added in the form of alginate.
  • the low sodium salt is a particle having a particle diameter of from 250 micrometers to 1 millimeter.
  • the preparation method of the low-sodium salt comprises granulation using a salt of a poly-alginate of more than 150 ⁇ m adhered to a salt powder of 50 ⁇ m or less or a pressure of 40 MPa to 100 MPa and then pulverizing to have a particle diameter of 250 ⁇ m to 1 mm.
  • Low sodium salt granules Low sodium salt granules.
  • the present application also provides a process for the preparation of the oligomeric alginate comprising preparing an oligomeric alginic acid according to the method described above and then forming a low sodium salt comprising an oligomeric potassium alginate (sodium).
  • the invention provides a method for preparing a low sodium salt, which comprises the steps of: using a sodium chloride powder having a particle size of more than 150 micrometers and a sodium chloride powder having a particle size of 50 micrometers or less or less according to the mass ratio of the components; Granules or granules of sodium chloride powder having a particle size of more than 150 ⁇ m adhered to a particle size of 50 ⁇ m or less and then pulverized using a pressure of 40 MPa to 100 MPa to obtain a low sodium salt particle having a particle size of 250 ⁇ m to 1 mm. .
  • the method for preparing a low sodium salt of the present application comprises the steps of: spraying in an oligomeric alginate powder having a d 50 of 258 micrometers to 270 micrometers according to the ratio of the components.
  • the oligopeptide solution is mixed, and then NaCl powder having a d 50 of 39 ⁇ m to 50 ⁇ m is added, granulated on a granulator, dried, and sieved using a 280 ⁇ m sieve to obtain a low oligomeric potassium alginate and an oligopeptide.
  • the sodium salt was determined to have a d 50 of 498 ⁇ m to 640 ⁇ m; the remaining NaCl was left for the next preparation of a low sodium salt sample containing oligomeric potassium alginate and oligopeptide.
  • a method for preparing a low sodium salt comprises the steps of: spraying an oligopeptide solution in an oligomeric potassium alginate powder having a d 50 of 258 micrometers to 270 micrometers according to the ratio of the components; Mixing, adding NaCl powder having a d 50 of 39 ⁇ m to 50 ⁇ m, granulating on a granulator, and preparing the mixture on a Herzog tablet press using a pressure of 40 MPa to 100 MPa; then, the obtained pellet is broken along the diameter, And sieving in a sieve mill to obtain low sodium salt particles having a d 50 of 398 ⁇ m to 520 ⁇ m.
  • a method for preparing a low sodium salt comprises the steps of: oligomerizing alginate and oligopeptide and remaining components other than sodium chloride according to the weight ratio Mixing and preparing a composition solution of 20% dry polyalginate and oligopeptide on a dry basis, according to the composition of the oligomeric alginate and oligopeptide, the solution temperature is 60 ° C ⁇ 80 ° C, the spray speed 25 ⁇ 35 liters/hour, sodium chloride fine-grained material having a diameter of less than 600 ⁇ m, 12 kg to 25 kg, coated with sodium chloride fine-grained material by boiling drying to obtain d 50 containing oligomeric alginate and oligopeptide It is a 630 micron low sodium salt sample; the boiling drying conditions are a solution of a composition of a bottom spray of an oligomeric alginate and an oligopeptide or a top spray of a composition solution of an oligomeric alginate and an oligopeptide
  • the application provides a method of preventing or adjuvant treatment of hypertension comprising administering to the subject the above-described potassium oligo-alginate.
  • oligomeric potassium alginate daily intake is 2.8 g /60kg.
  • the present application also provides a method of preventing or assisting in the treatment of hypertension comprising administering to the subject a low sodium salt as described above.
  • oligomeric (low molecular) potassium alginate not only has a potassium-sparing effect, but also because the oligomeric (low-molecular) potassium alginate contains small molecules of potassium alginate, which converts small molecules of alginic acid into small intestines.
  • Molecular sodium alginate can be absorbed into the blood vessels through the intestinal mucosa, and the small molecule sodium alginate has a calcium channel blocker, which lowers blood pressure.
  • the above-mentioned amount of oligomeric potassium alginate can significantly increase the amount of urinary sodium and urinary potassium excretion, and can significantly increase serum potassium levels, but has no significant effect on fecal sodium and fecal potassium excretion and serum sodium concentration. It is confirmed that the oligomeric potassium alginate can act as a potassium-sparing sodium in the body.
  • the hypotensive mechanism of oligo-polyaluminate is at least related to the diuresis of the test article and the increase of urine and fecal sodium excretion.
  • Potassium oligo-alginate is suitable for people who need potassium supplementation and a tendency to have cardiovascular and cerebrovascular diseases.
  • the large-scale production of low-poly potassium alginate samples is calculated according to the body weight of 60Kg, and the daily service is 2.8g each time.
  • the auxiliary blood pressure lowering effect can fully meet the national health food requirements.
  • the antihypertensive effect has a long half-life (up to 144 hours), and large-scale production of oligomeric potassium alginate is added to various foods (eg: Salt, dairy products, condiments, etc.), the daily dose is not more than 6.0 grams in terms of salt.
  • the addition of oligopeptides to low-sodium salts containing oligomeric potassium alginate can increase the umami taste, making the low-sodium salt a savory condiment, which is more popular with consumers.
  • pancreatic amylase has the highest activity at pH 6.9-7.0; trypsin has the highest activity at pH 8. So in the small intestine, the food is completely decomposed, and protein, starch, and fat are broken down into amino acids, glucose, fatty acids, and glycerin.
  • Potassium alginate is orally administered into the stomach.
  • the pH of the gastric juice is 1-3.5 potassium alginate and gastric acid, forming a gel. Most of the potassium ions are quickly absorbed into the blood vessels from the small intestine.
  • the carbonic acid in the pancreatic juice Sodium hydride forms part of the intestinal fluid, and the pH of the intestinal fluid is 7.8-8.0.
  • the pH of the large intestine is 8.3-8.4.
  • Alginic acid reacts with alkaline sodium bicarbonate in the intestinal juice to convert it into sodium alginate. After the colon and rectum absorb water, the sodium alginate converted into rectal alginate becomes part of the feces. Excreted from the body, potassium supplementation is achieved.
  • the purpose of the present application is to provide a low sodium salt containing oligomeric potassium alginate.
  • the low sodium salt provided by the present application comprises sodium chloride and potassium oligomeric potassium alginate, wherein the oligomeric potassium alginate has a weight average molecular weight of 700 Daltons to 10,000 Daltons and a Ubbel viscosity of 3-16. And the molar ratio of the mannuronic acid unit to the guluronic acid unit in the alginic acid is 0.3-3.3.
  • the oligomeric alginic acid in the oligomeric potassium alginate of the present application has a weight average molecular weight of 1,000 Daltons to 4,500 Daltons, and the mannuronic acid unit and the ancient oligomeric alginic acid
  • the molar ratio of the saccharuronic acid unit is from 0.4 to 3.3.
  • the method of preparing the above oligomeric alginic acid provided by the present application includes a conventional degradation step.
  • the method comprises degrading alginic acid having a weight average molecular weight of from 10,000 Daltons to 1,500,000 Daltons, the degradation step comprising a physical degradation step, a photochemical degradation step, an immobilized enzyme degradation step, and a chemistry
  • the degradation step comprising a physical degradation step, a photochemical degradation step, an immobilized enzyme degradation step, and a chemistry
  • One or several degradation steps in the degradation step is performed prior to the degradation step.
  • the physical degradation step, the photochemical degradation step, the immobilized enzyme degradation step, and the oxidative degradation step are well known in the art and are described in detail in PCT/CN99/00202, the entire disclosure of which is incorporated herein by reference.
  • the physical steps include ultrasonic treatment or high-speed shear treatment;
  • the photochemical step is treatment using optical radiation and catalysis;
  • the oxidative degradation step includes using an organic oxidant and/or an inorganic oxidant such as hydrogen peroxide, peracetic acid, potassium peroxide, or Oxidized potassium carbonate, potassium perborate (sodium), potassium permanganate, ammonium persulfate, potassium persulfate double salt, potassium chlorite, sodium chlorite, etc.
  • immobilized enzyme degradation step includes immobilization of algae using a porous sodium glass ball carrier After the acid decomposing enzyme, the column is decomposed.
  • the oligomeric potassium alginate is the weight average molecular weight of the potassium salt oligomeric alginic acid of the oligomeric alginic acid and the molar ratio of the mannuronic acid unit (M) to the guluronic acid unit (G) can be used in the field.
  • M mannuronic acid unit
  • G guluronic acid unit
  • a commonly used method for determining, for example, the oligomeric alginic acid product obtained by degrading alginic acid is reacted with a basic substance (for example, sodium hydroxide) to obtain a soluble salt of oligomeric alginic acid, using the mini DAWN TREOS of Wyatt (WTC), USA.
  • the molecular weight and molecular weight distribution of the oligomeric alginate were determined by laser light scattering apparatus and 150c, PL220c and ALLIANCE 2000 of Waters Corporation of the United States according to the instruction manual, and the weight average molecular weight was calculated.
  • the molar ratio of the mannuronic acid unit to the guluronic acid unit can be determined by chemical method, and the sample is subjected to acid hydrolysis to form a single mannuronic acid unit and guluronic acid.
  • the mixture of the unit is separated by anion exchange resin and eluted, and the mixture of the mannuronic acid unit and the guluronic acid unit can be separated, and the mannose unit and the guluronic acid unit are respectively measured by color development.
  • the total absorbance value is calculated, and the molar ratio of G to M can be obtained by calculation.
  • the content of monomers in G, M, GG, MM, and GM in alginic acid can also be determined by nuclear magnetic resonance (NMR).
  • the above method for measuring the molecular weight is a viscosity method.
  • the viscosity method is used to determine the molecular weight, the equipment required is relatively simple, and the operation is easy to grasp, such as measuring the Ubbelohde viscosity, which is commonly used for the molecular weight determination of polysaccharides.
  • Ubbelohde viscometer capillary length is 140 nm ⁇ 5 nm, inner diameter is 0.5 nm ⁇ 0.05 nm, and B sphere volume is 3.35 mL ⁇ 0.5 mL.
  • the effluent time measured with distilled water should be between 120 seconds and 180 seconds.
  • the stop time of the solution was accurately determined using a stopwatch.
  • the effluent time of each concentration (C 1 , C 2 , C 3 ...) was read, and the temperature at the time of the test was generally a constant temperature water bath of 25 ° C ⁇ 0.05 ° C.
  • the oligomeric potassium alginate is an Ubbelohde viscosity meter used to control the average molecular weight.
  • the pH of potassium alginate in a 1% aqueous distilled solution was about 7.3.
  • the degree of polymerization (DP) and molecular weight are directly related to the viscosity of the potassium alginate solution.
  • the oligomeric potassium alginate is obtained by neutralizing the above oligomeric alginic acid with a potassium-containing basic compound.
  • the weight ratio of sodium chloride to potassium oligo-alginate in the low sodium salt of the present application is (48-83): (13-40); and the specific range may also be (64). -77): (15-22), (64.6-76.9): (15.38-22). Specifically, the sodium chloride accounts for 48%-83% of the total weight of the low sodium salt, and specifically may be 64.6%-76.9%. The oligomeric potassium alginate accounts for 13%-40% of the total weight of the low sodium salt; specifically, it may be 15.38%-22%.
  • the sodium chloride containing material can be derived from several different sources, such as sea salt, rock salt, refined (vacuum) salt or synthetic salt source.
  • the low sodium salt further includes an additive selected from the group consisting of a taste improver, a taste masking agent, a mineral, an anti-caking agent or a flow additive, a taste improver, a taste masking agent, a mineral, and an anti-caking agent.
  • an additive selected from the group consisting of a taste improver, a taste masking agent, a mineral, an anti-caking agent or a flow additive, a taste improver, a taste masking agent, a mineral, and an anti-caking agent.
  • the weight ratio of the sodium chloride, the oligomeric potassium alginate, the oligopeptide and the additive is (48-83):(13-40):(3.8-11.5):(0.2-0.5).
  • the specific weight ratio may be (64-77):(15-22):(5-8):(0.2-0.5), and may also be (64.6-76.9):(15.38-22):(5.8-7.76) : (0.2-0.5).
  • a low sodium salt product is defined to include both products in which a portion of the sodium chloride is replaced by an oligomeric potassium alginate (also referred to herein as a sodium chloride replacement material, such as an oligomeric potassium alginate).
  • a material containing a sodium chloride and sodium chloride replacement material is referred to as a "sodium chloride containing material"
  • the product may also contain at least one additive (eg, a flavor enhancer) a product of a taste masking agent, a nutrient or any other additive; and a product that produces a strong salty taste by adding an additive that acts as a so-called flavor enhancer to ensure that the same taste is experienced with a lower amount of sodium chloride.
  • Substantially dry in the present application refers to a free water content of less than 3% by weight, typically less than 1% by weight, based on the (total) solids.
  • Free water refers to any water that can evaporate (from particles) at 100 °C.
  • the low sodium salt of the present application may also include an additive, which in one embodiment is selected from a material that inhibits, enhances, affects or alters the taste and/or flavor, or a food product that affects the salt product or may use the salt product of the present application.
  • an additive which in one embodiment is selected from a material that inhibits, enhances, affects or alters the taste and/or flavor, or a food product that affects the salt product or may use the salt product of the present application.
  • the additive may be a synthetic additive such as a synthetic additive derived from a natural source.
  • the additive is a taste/flavor enhancer (taste improver), a taste/flavor masking agent (eg, an unpleasant taste (bitter or metallic taste) that masks the sodium chloride replacement material), and is resistant. Agglomerating agent or flow additive.
  • the additive is a flavor Road/flavor enhancer or taste/flavor masking agent. Since these two types of taste enhancing and taste masking agents often overlap, they are collectively referred to herein simply as "flavoring agents.”
  • the flavorant can be selected from materials known to those skilled in the art. Examples of materials suitable as odorants can be found, for example, in WO 2004/075663.
  • the above taste/flavor enhancer or taste/flavor masking agent may be selected from the group consisting of edible organic acids such as succinic acid, citric acid; amino acids and derivatives thereof, such as glutamate /ester; yeast; yeast extract; hydrolyzed protein derived from yeast extract; peptide; hydrolyzed vegetable protein; hydrolyzed fat; ribonucleotide; flavonoid; amide of amino acid and dicarboxylic acid; trehalose; Salt; other flavoring or flavor modifying substances; or combinations thereof.
  • Other examples include organic acids such as lactic acid, malic acid; salts of organic acids; salts of ribonucleotides; products from Maillard reactions and fermented foods such as bean paste, fish sauce, sardines and cheese.
  • flavoring agent includes derivatives derived from allspice, basil, pepper, cinnamon, clove, cumin, dill, garlic, marjoram, nutmeg, red pepper, black pepper, a scented oily resin and oil of any of rosemary and turmeric; essential oils including fennel oil, coriander oil, clove oil, eucalyptus oil, fennel oil, garlic oil, ginger oil, peppermint oil, onion oil, pepper oil , rosemary oil and peppermint oil; citrus oils such as orange oil, lemon oil, bitter orange oil and tangerine oil; garlic flavors, including garlic, leeks, chives and onions; plant extracts, including arnica flower extract , chamomile extract, hop extract and calendula extract; plant extract extracts including blackberry, chicory root, cocoa, coffee, cola, licorice, rose hip, sassaparilla root, artichoke bark, tamarind , licorice and vanilla extract; protein
  • Representative stand-alone flavors include benzaldehyde, diacetyl (2,2-butanedione), vanillin, ethyl vanillin, and citral (3,7-dimethyl-2,6-octadienal) One or a combination of two or more of them.
  • additional additives may be added to the salt product.
  • additional additives may be selected from the group consisting of vitamins, acids, yeasts, amino acids, functional additives or nutrients such as fluorides, iodides, iodates, minerals, nitrites, nitrates, flavorings.
  • the low sodium salt of the present application contains sodium chloride (NaCl), oligomeric potassium alginate, and oligopeptide; the oligopeptide is an algae oligopeptide, a shellfish oligopeptide or corn. Oligopeptides or any combination of them.
  • the weight ratio of the sodium chloride, the oligomeric potassium alginate and the oligopeptide is (48-83): (13-40): (3.8-11.5); the specific weight ratio may be (64-77): ( 15-22): (5-8), which may also be (64.6-76.9): (15.38-22): (5.8-7.76).
  • the oligopeptide may comprise from 3.8% to 11.5% of the total weight of the low sodium salt.
  • the above oligopeptide is an enzymatic product of natural protein, wherein the algae oligopeptide is an enzymatic product of seaweed protein, the shell oligopeptide is an enzymatic product of shellfish protein, and the corn oligopeptide is an enzymatic solution of zein. product.
  • Algae and shellfish oligopeptides. Oligopeptides can increase umami taste and have an auxiliary blood pressure lowering effect.
  • the additives added to the sodium chloride-based product have a smaller particle size than the sodium chloride raw material, this is especially true when they involve organic additives other than the oligomeric potassium alginate.
  • organic additives other than the oligomeric potassium alginate.
  • yeast based additives have particle sizes well below 100 microns, while commercially available sodium chloride typically has particle sizes of hundreds of microns. If these two materials are mixed, separation will occur during transportation and storage. Agglomeration is the way to avoid this layering. However, after pressing and pulverizing to the desired particle size, smaller particles will appear on the outer surface of the particles, causing additive loss.
  • the method of the present application can improve the moisture absorption resistance by coating a composition of an oligopeptide with an oligomeric potassium alginate on the surface of the sodium chloride fine particles.
  • the low sodium salt product of the present application consists, for example, of free flowing particles.
  • the comminuting step includes any method of reducing the particle size and includes methods such as crushing, crushing or grinding.
  • the components may be one in which two or more are pulverized together in one comprehensive step, or pulverized by a separate pulverization step. If sodium chloride is used instead of the material in the process, it can be comminuted with sodium chloride or comminuted separately.
  • the pressing step includes any method of agglomerating the particles by applying an external force, and the pressure for pressing the mixture of particles is the pressure applied in the unidirectional pressing of the pellets (causing a certain density of the pressed particle mixture).
  • pressing can be suitably carried out by other presses such as a roll press.
  • the pressure used is the pressure that causes the same compacted physical density as in unidirectional pressing.
  • the pressing step includes any method of agglomerating the particles by applying an external force, for example, by applying an external force under a pressure of 40 MPa to 100 MPa to agglomerate the particles.
  • the process of the present application may, in one embodiment, comprise a subsequent step in which the material is screened to separate particles of the desired composition, or particles of the desired particle size range.
  • the low sodium salt product has a particle size of 250 micrometers to 1 millimeter, and is granulated with a salt of a polyaluminium alginate of more than 150 micrometers and adhered to a particle size of 50 micrometers or less or 40 MPa to 100 mg.
  • the pressure of MPa is pulverized to obtain a mixture of oligomeric potassium alginate and salt particles; to produce particles having a desired particle size of from 250 micrometers to 1 millimeter; wherein the steps are carried out under substantially dry conditions.
  • the product obtained by this method is actually characterized by more uniform mixing of the additive into the sodium chloride-containing particles, and also has good separation resistance and abrasion resistance.
  • the oligomeric potassium alginate powder (d 50 is 258 micrometers to 270 micrometers) is sprayed with the algae oligopeptide solution, and after mixing, the NaCl powder is added (d 50 is 39 micrometers to 50 micrometers, The granules were granulated, dried, and sieved to obtain a low sodium salt containing oligomeric potassium alginate and algae oligopeptides using a 280 micron sieve, and determined to have a d 50 of 498 micrometers to 640 micrometers. A sample of a low sodium salt containing an oligomeric potassium alginate and an algae oligopeptide was prepared at one time.
  • the oligomeric potassium alginate powder (d 50 is 258 micrometers to 270 micrometers) is sprayed with the algae oligopeptide solution and mixed, and the NaCl powder is added (d 50 is 39 micrometers to 50 micrometers, Granulation was carried out on a granulator, and 50 g of pellets (40 mm diameter, 20 mm height) were produced from this mixture on a Herzog tablet press using a pressure of 1.0 t/cm 2 (corresponding to a pressure of 100 MPa). Broken and sieved on a Frewitt screen mill using 6 mm, 3 mm and last 1 mm screens.
  • the products from the Frewitt screen mill were sieved into fractions using 710 micron, 500 micron, 280 micron and 90 micron sieves. Further analysis of the fractions 280 micrometers to 710 micrometers (i.e., two fractions were combined), and determined to have a d 50 398 microns -520 microns.
  • a combination of potassium oligomeric alginate and oligopeptide and the remaining components other than sodium chloride is prepared as a combination of 20% dry polyaluminate and oligopeptide on a dry basis.
  • Solution according to the composition of the oligomeric potassium alginate and oligopeptide solution, the material temperature is 40 ° C ⁇ 60 ° C, 60 ° C ⁇ 80 ° C, 80 ° C ⁇ 100 ° C, the spray speed of 20 ⁇ 25 l / h, 25 ⁇ 35 liters / hour, 35 ⁇ 40 liters / hour for screening, the results: the composition of the oligomeric alginate and oligopeptide solution material temperature is 40 ° C ⁇ 60 ° C, the material temperature is too low, the powder is not easy to dry, easy Agglomeration.
  • the spray speed is 20 to 25 liters/hour, the spray speed is low, and the flow rate is small, which affects efficiency.
  • the spray speed is 35-40 liters/hour, the spray speed is fast, the powder is not easy to dry completely, and it is easy to agglomerate.
  • the temperature of the material is from 80 ° C to 100 ° C, the temperature of the material is too high, which may cause decomposition of the active ingredients in the intermediate of the composition. Therefore, the composition of the composition of the oligomeric alginate and the oligopeptide is selected to have a temperature of 60 ° C to 80 ° C, a concentration of 20%, and a spray rate of 25 to 35 liters per hour as a fine particle material of less than 600 ⁇ m in diameter.
  • the sodium chloride fine-grained material is subjected to functional potassium alginate coating granulation by boiling drying conditions.
  • the boiling drying conditions were respectively as follows: a bottom sprayed potassium alginate seaweed peptide composition solution, and a top sprayed potassium alginate seaweed peptide composition solution were used to obtain a stable quality d-containing potassium alginate algae peptide having a d 50 of 630 micron low sodium salt. sample.
  • the weight ratio of sodium chloride, oligomeric potassium alginate and oligopeptide is (48-83): (13-40): (3.8-11.5).
  • the specific weight ratio may be (64-77):(15-22):(5-8), and may also be (64.6-76.9):(15.38-22):(5.8-7.76).
  • seaweed oligopeptides in the present application are prepared as follows: an enzymatic hydrolysis method and an exogenous enzyme technique are employed.
  • Protein enzymatic engineering is performed by endopeptidase and exonuclease.
  • the hydrolysate of the former is a polypeptide
  • the hydrolyzate of the latter is a free amino acid. Therefore, by adding an endonuclease or adding an exonuclease to increase the hydrolysis ability, the protein species and amino acid composition ratios in different hydrolyzed raw materials are different, so the enzyme The choice of enzymes and the hydrolysis conditions of the enzymes are also significantly different.
  • the exogenous enzyme technology can be divided into single enzymatic hydrolysis technology, double enzyme enzymatic hydrolysis technology and multi-enzyme complex enzymatic hydrolysis technology.
  • the single enzyme method is a method of hydrolyzing a protein in a raw material by using only one exogenous enzyme to obtain a hydrolyzed protein.
  • the orthogonal conditions were used to optimize the hydrolysis conditions, and the neutral protease of Bacillus subtilis was determined to be the best, and the degree of hydrolysis was 60%-62.6%.
  • the hydrolysis rate can reach 69.0%.
  • the multi-enzyme complex method is a method of hydrolyzing a raw material protein with two or more enzymes.
  • the multi-enzyme complex enzymatic hydrolysis technique is firstly carried out by mixing the endopeptidase for a short time to hydrolyze the protein into peptides, the structure becomes loose, and then the enzyme is heated up, and then the flavor protease (Flavourzyme) is added to carry out the second stage under suitable conditions.
  • Enzymatic hydrolysis the degree of hydrolysis can reach 68.2%, and the hydrolyzate has a unique and delicious flavor.
  • the multi-enzyme method utilizes the specificity of various proteases to fully hydrolyze the raw material protein into amino acids and terminal peptides, and the resulting amino acids and peptides make the hydrolyzate taste more delicious.
  • the fixed hydrolysis temperature was adjusted to 50 ° C. When other factors were constant, the different hydrolysis time was controlled. The hydrolysis time was taken as the abscissa, and the amino acid content in the sample solution was plotted on the ordinate. The results showed that the hydrolysis time was in the range of 2 hours to 4 hours. The internal hydrolysis is not obvious, and the hydrolysis rate is slowly increased. As the hydrolysis time prolonged, the amount of amino acids gradually accumulated. When the hydrolysis time reached 4 hours, the hydrolysis rate increased rapidly, and the rate of increase slowed down after 6 hours. After a certain period of time, the amino acid concentration accumulates to a larger concentration, and then continues to hydrolyze. The amino acid content increases little.
  • the hydrolysis efficiency can be significantly improved.
  • the present application also provides the use of the above low sodium salt in preventing hypertension or preparing a product or food for preventing hypertension.
  • Dalian Yaweite Biotechnology Co., Ltd. uses commonly used process technologies such as thermal degradation, oxidation, ultrasonic degradation, acid degradation, alginic acid lyase method alone or in combination to use high molecular weight algae
  • the acid is degraded into oligomeric alginic acid having a small molecular weight, and then neutralized with a potassium-containing base to obtain an oligomeric potassium alginate.
  • the process technology for preparing oligomeric potassium alginate has matured. In the past 10 years, it has been found through pharmacodynamic experiments that the Ub-waste viscosity of the potassium alginate sample decreases spontaneously under the condition of maintaining the pressure-reducing efficiency.
  • the amount of potassium alginate fed by hypertensive rats was reduced, and the viscosity of potassium oligomeric alginate developed by Dalian Yavit Biotechnology Co., Ltd. was 3-16.
  • a number of animal tests have shown that low-poly potassium alginate does have a potassium-sparing effect, and its effect is far better than potassium chloride.
  • oligomeric (low molecular) potassium alginate not only has a potassium-sparing effect, but also because the oligomeric (low-molecular) potassium alginate contains small molecules of potassium alginate, which converts small molecules of alginic acid into small intestines.
  • Molecular sodium alginate can be absorbed into the blood vessels through the intestinal mucosa, and the small molecule sodium alginate has a calcium channel blocker, which lowers blood pressure.
  • the above-mentioned amount of oligomeric potassium alginate can significantly increase the amount of urinary sodium and urinary potassium excretion, and can significantly increase serum potassium levels, but has no significant effect on fecal sodium and fecal potassium excretion and serum sodium concentration. It is confirmed that the oligomeric potassium alginate can act as a potassium-sparing sodium in the body.
  • the hypotensive mechanism of oligo-polyaluminate is at least related to the diuresis of the test article and the increase of urine and fecal sodium excretion.
  • Potassium oligo-alginate is suitable for people who need potassium supplementation and a tendency to have cardiovascular and cerebrovascular diseases.
  • the large-scale production of low-poly potassium alginate samples is calculated according to the body weight of 60Kg, and the daily service is 2.8g each time.
  • the auxiliary blood pressure lowering effect can fully meet the national health food requirements.
  • the antihypertensive effect has a long half-life (up to 144 hours), and the large-scale production of low-polyaluminium alginate is added to various foods (such as salt, dairy products, condiments, etc.), and the daily dosage is 6.0.
  • the low sodium salt containing potassium alginate can increase the umami taste by adding the algae oligopeptide, making the low sodium salt a savory seasoning, which is more popular with consumers.
  • pancreatic amylase has the highest activity at pH 6.9-7.0; trypsin has the highest activity at pH 8. So in the small intestine, the food is completely decomposed, and protein, starch, and fat are broken down into amino acids, glucose, fatty acids, and glycerin.
  • Potassium alginate is orally administered into the stomach.
  • the pH of the gastric juice is 1-3.5 potassium alginate and gastric acid, forming a gel.
  • Most of the potassium ions are quickly absorbed into the blood vessels from the small intestine.
  • the carbonic acid in the pancreatic juice Sodium hydride forms part of the intestinal fluid, and the pH of the intestinal fluid is 7.8-8.0.
  • the pH of the large intestine is 8.3-8.4.
  • Alginic acid reacts with alkaline sodium bicarbonate in the intestinal juice to convert it into sodium alginate. After the colon and rectum absorb water, the sodium alginate converted into rectal alginate becomes part of the feces.
  • Excreted from the body potassium supplementation is achieved. For people with chronic renal failure who are not suitable for potassium alginate, it is a suitable choice to use low-alcohol sodium alginate to assist blood pressure reduction.
  • Potassium oligo-alginate is prepared by using sodium alginate as raw material, acidified with hydrochloric acid in ethanol, and converted into alginic acid by acidification, separating acidified ethanol, using water as solvent, and using potassium hydroxide as pH adjuster to seaweed.
  • the chemical conversion of the acid to the potassium salt of alginic acid is as follows:
  • Salt formation After the degradation treatment is completed, cooling water is introduced into the reaction jacket interlayer to lower the temperature of the reactants to the salt formation temperature, and the pH adjustment liquid can be slowly added to the reaction product to form a solution.
  • Salt reaction the pH value of the reactants is measured at any time during the reaction, until the pH reaches a stable 7.5-8.0, the alkali is stopped, the alginate lyase is added, and the alginate lyase is added every 10 kg according to the dry weight of potassium alginate. 10 liters of liquid.
  • the specific activity of the alginate lyase was 1800 U/MG, and the cleavage temperature was controlled at 40 ° C for 5 hours.
  • Deodorization and decolorization According to the volume (L) of the potassium alginate solution after salt formation, add 1% activated carbon, and stir to 60 ° C ⁇ 70 ° C for 60 minutes under stirring conditions, then the delivery can be sent The next process.
  • the potassium alginate aqueous solution obtained by the purification and purification process is concentrated to increase the solid content of the solution.
  • the concentrated potassium alginate solution is prepared into a fine powder of potassium alginate by a drying method, and then placed in a natural state to be cooled to room temperature, and then purified water is used as a wetting agent, and a granulated powder of 40 mesh to 250 mesh is prepared by using a granulating dryer, that is, Obtained oligomeric potassium alginate.
  • Preparation of oligomeric sodium alginate using sodium alginate as raw material acidification of hydrochloric acid with hydrochloric acid, conversion of sodium alginate into alginic acid, separation of acidic ethanol, use of water as solvent, sodium hydroxide as pH adjuster, Other processes and equipment used are the same as for the preparation of oligomeric potassium alginate.
  • the oligomeric potassium alginate prepared has a Ubbel viscosity of 3-16; the average molecular weight is 700 Dalton to 10,000 Dalton; the molar ratio of the mannuronic acid unit to the guluronic acid unit is 0.3. -3.3.
  • the oligomeric potassium alginate sample is prepared as a granule or a powder. Calculated according to the body weight of 60Kg, the daily service once, 2.8 grams each time, the auxiliary blood pressure lowering effect can fully meet the national health food requirements.
  • the antihypertensive effect has a long half-life (up to 144 hours), and the low-polyaluminate potassium alginate is added to various foods (such as dairy products, condiments, etc.), and the low-poly potassium alginate intake of 2.8 g or more can reach the national health care.
  • Auxiliary blood pressure lowering standards for food requirements are provided.
  • the test population chose spontaneous hypertensive patients.
  • the test population consisted of 30 people in each group.
  • the control group received 35% potassium chloride and low sodium salt as the control group.
  • the daily intake of low-sodium salt containing 35% potassium chloride was 9.0 g, of which sodium chloride was 5.9. Gram, 3.1 grams of potassium chloride.
  • Ingestion of low-concentration potassium alginate was used as a test group, and 2.8 g of low-concentration potassium alginate was ingested daily.
  • One month was ingested, and the systolic and diastolic blood pressure of each ingestor was tested every day. The observation results are shown in Table 1-4 below.
  • the composition is as follows: water 15-18, protein 10-16, fat 1-2, sugar 38-45 (about alginic acid 20), fiber 2-3. Ash is 18-30.
  • seaweed contains aspartic acid 3.40, leucine 2.72, lysine 1.34, alanine 2.7, and valine 1.48. In addition to the above various nutrients, it also contains a large amount of iodine and various other soluble metal trace element nutrients.
  • the seaweed raw material is pulverized and poured into a stainless steel reaction pot with a sandwich.
  • the seaweed is immersed in a 5% acetic acid solution, soaked for 24 hours to dissolve the acid-soluble substance therein, and then the acetic acid is discharged from the bottom drain pipe wrapped with the multi-layer gauze, and then Inject the deionized water repeatedly and soak. Thoroughly rinse the residual acetic acid until the pH of the solution is neutral.
  • 80 ° C then open the automatic stirrer in the reaction pot, slowly add 10% NaOH solution while stirring, adjust the pH of the solution to 8.0, and continue stirring until the seaweed in the reaction pot is paste.
  • the purpose of heating and adding alkali is: 1) killing bacteria in the solution, preventing bacterial growth during enzymatic hydrolysis and reducing the nutritional value of seaweed protein; 2) since seaweed is insoluble in water, but soluble in hot alkali solution Therefore, the addition of NaOH solution can play a role in solubilization; 3) the action of heat and alkali can degenerate seaweed, the spatial structure of the protein changes, the chemical bond between the peptide chains breaks, and it is more easily decomposed by proteases; 4) adjust the pH of the solution So that trypsin can exert maximum biological activity.
  • the enzymatic hydrolysis reaction was started under continuous stirring with a stirrer, during which the amount of steam introduced into the reaction vessel interlayer was adjusted to maintain the temperature at 50 °C.
  • the protein of algae is continuously decomposed to form a polypeptide due to the hydrolysis of trypsin, and the polypeptide continues to be decomposed into short-chain peptides, even in the action of amine peptidase or aminopeptidase.
  • a small amount of free amino acids is produced. Since the polypeptide, small peptide or amino acid is an ampholyte and the isoelectric point is mostly acidic, the pH of the whole reaction system will decrease continuously with the formation of the peptide during the reaction, so as to ensure the maximum biological activity of the trypsin.
  • the pH of the liquid was maintained at 8.0, which required constant addition of a dilute NaOH solution to the reaction solution.
  • the enzymatic reaction was completed 6 hours after the addition of trypsin. At this time, increase the amount of steam to make the enzymatic hydrolysate to 80 ° C for 30 min, the role of which is two: one is to inactivate the trypsin to stop the enzymatic hydrolysis; the second is to kill the bacteria in the reaction solution again Bacteria proliferate during subsequent processing.
  • the enzymatic reaction solution was filtered through a plate and frame filter press and a microfiltration compressor, respectively.
  • the filter membrane of the plate and frame filter press is a thickened filter paper which is strengthened by two layers of thick cotton gauze.
  • the microfiltration compressor adopts a quartz filter with a filter pore size of 0.5 ⁇ m, and the two are filtered to remove the larger size of the pancreatin preparation in the reaction liquid. Particles.
  • the quartz filter element is placed in a 5% NaOH diluted solution for cleaning, and then rinsed with distilled water to ensure the best filtration effect.
  • the filtered enzymatic hydrolysate was neutralized by adding 10% hydrochloric acid to adjust the enzymatic hydrolyzate to neutrality.
  • 10% hydrochloric acid to adjust the enzymatic hydrolyzate to neutrality.
  • a considerable amount of NaOH is added, followed by neutralization by hydrochloric acid to convert into a large amount of sodium chloride, and sodium chloride accounts for the weight ratio of seaweed protein. More than 10%.
  • the vacuum concentration pump is used to carry out vacuum low-temperature concentration, so that a large amount of water in the solution is evaporated under vacuum and low pressure, and then spray-dried through a drying tower, and finally a small peptide preparation produced by trypsin hydrolyzing algae protein is obtained to obtain an algae oligopeptide.
  • Papain enzymatic hydrolysis of seaweed (kelp) protein the temperature increased from 40 ° C to 50 ° C, amino nitrogen dissolution increased significantly.
  • the increase is not obvious and tends to decrease with increasing temperature. This is because proper heating makes the protein structure loose, exposes more enzyme sites, and the enzyme activity also reaches the optimal state.
  • the enzyme activity gradually decreases, resulting in a decrease in the amino nitrogen content. Therefore, we chose 50 ° C for the optimum temperature of hydrolysis.
  • the maximum reaction temperature of the enzyme was 60 ° C. Under this temperature condition, 70% of the enzyme activity was maintained in the warm bath for 100 min.
  • the optimal hydrolysis process for papain hydrolysis Single factor experiments showed that papain hydrolysis was carried out at a temperature of 50 ° C for about 5 h, a substrate concentration of 4%, an enzyme loading of about 5,500 U/g to 10,000 U/g, a pH of 7.0 to 7.5. The effect is better.
  • Orthogonal test showed that the order of influence of the three factors was: enzyme amount>substrate concentration>hydrolysis time; the optimal hydrolysis process was: pH value of 7.5 of hydrolysate, and enzyme amount was 5,500 U/g-10,000 U/g, bottom
  • the concentration of the substance is 4%, the temperature is 50 ° C, and the hydrolysis is 6 h. Under this condition, the degree of hydrolysis can reach 37.89%.
  • the enzymatic hydrolyzate with higher hydrolysis degree can be obtained by hydrolysis with papain.
  • Acute toxicity test the maximum tolerated dose test of mice and rats.
  • the oligomeric potassium alginate prepared in Example 1 was fed during the observation period in both sex mice and rats.
  • the drinking water activity was normal, no poisoning phenomenon, fur Bright, no death.
  • the maximum tolerated dose of the sample to both sex mice and rats was greater than 4.50g/kg.BW;
  • Ames test the number of reverting colonies in each dose group did not exceed 1 times of the number of colonies in the sample solvent control group, and there was no dose-response relationship.
  • Micronucleus test of mouse bone marrow cells The ratio of bone marrow polychromatic erythrocytes to mature red blood cells (PCE/NCE) in the two sex groups of the two sex groups was between 1.25 and 1.36.
  • Mouse sperm abnormality test There was no significant difference in the sperm deformity rate between the mice in each dose group and the sample solvent control group (P>0.05), while the sperm abnormality rate in the cyclophosphamide group was compared with the sample solvent control group. There was a significant difference (P ⁇ 0.01). No samples were found to have significant damage to male mouse germ cells.
  • the test results were obtained: the results of the acute toxicity test showed that the maximum tolerated dose of potassium oligo- alginate prepared in Example 1 was greater than 4.50 g/kg. BW for both sexes. All three genotoxicity tests were negative, indicating that the oligomeric alginate has no genotoxic effects.
  • the oligomeric potassium alginate is obtained by degrading the high-molecular potassium alginate as a raw material, and the degradation process is essentially a process of purifying impurities such as polyphenols, proteins and complex carbohydrates, and oral refined potassium alginate is not used. An allergic reaction can occur.
  • the systolic blood pressure of SHRs was measured by tail pulse indirect pressure measurement.
  • 40 rats were randomly divided into 5 groups: blank vehicle control group, hydrochlorothiazide tablet group (6.25 mg/kg), low-alcoholic potassium alginate high dose, medium dose and Low-dose group (500mg/kg, 250mg/kg, 100mg/kg), intragastric administration of hypo-alkali potassium alginate, continuous administration of hypo-aluminum alginate 28d; weekly blood pressure measurement, and observed 3d, 6d after stopping Blood pressure changes.
  • SHRs rat feces were collected for determination of sodium content in the feces.
  • mice Male SD rats, weighing 180g-220g, were provided by the Animal Center of Chengdu University of Traditional Chinese Medicine. Feeding conditions 20 ° C ⁇ 2 ° C, 12 h / 12 h circadian rhythm. Animals were housed in rat metabolic cages and fed freely with water.
  • the low molecular weight potassium alginate (PA) prepared in Example 1 was light yellow powder and was dissolved in rat drinking water daily for free drinking.
  • nitric acid analytically pure, colorless transparent liquid
  • batch number 20071108 Chengdu Xinhaixing Chemical Reagent Factory, dissolved in distilled water before use to prepare 10% nitric acid solution. Used for sodium-free treatment of containers.
  • Nitric acid excellent grade pure, colorless transparent liquid, batch number 090211, Sichuan Xiqiao Chemical Co., Ltd., directly used for sample digestion.
  • Perchloric acid excellent grade pure, colorless transparent liquid, batch number 20080708, Tianjin Dongfang Chemical Factory, directly used for sample digestion.
  • Benchtop centrifuge 4000 ⁇ 40000 rpm, model TGL-16G, Shanghai Anting Technology Instrument Factory.
  • Eppendorf adjustable pipette 100 ⁇ L - 1000 ⁇ L, eppendorf, Germany.
  • Preparation of 0.5% NaCl drinking water Take 125mL of 2.0% NaCl drinking water, add distilled water to make up to 500mL, that is;
  • PA drinking water Weigh 0.625g of low molecular weight potassium alginate powder, dissolve it in 2.0% NaCl drinking water, and finally make up to 625mL;
  • PA drinking water Take 125 mL of 2.0% NaCl-PA drinking water, and add distilled water to make it to 500 mL.
  • Preparation of 10% nitric acid solution Take 1000 mL of 68% concentrated nitric acid solution and add 5800 mL of distilled water to obtain.
  • Metabolic cages, EP tubes, and conical flasks for collecting serum, urine, and feces were immersed in a 10% nitric acid solution overnight, and then rinsed with deionized water for drying.
  • Rats were fed with free water and measured the amount of water, food intake and urine volume of rats 24 hours a day. On the 0th, 30th, and 60th day of feeding, the blood was taken from the tail vein and the serum was routinely separated. The rats were given a 24h urine sample. Fecal sample. Serum and urine samples were stored at -20 ° C until use. Treatment of fecal samples: After the feces were dried for 60 hours at 60 hours, they were ground and placed in a desiccator for storage.
  • Table 6 shows that at the 60th day of administration, compared with the 0.5% NaCl model group, the rats in the experimental group with 0.5% NaCl/0.025% oligo-alginate had a slight increase in urinary sodium excretion, at doses 30 and 60. At the time of day, the excretion of urinary potassium also increased, but the difference was not statistically significant (P>0.05).
  • the urinary sodium excretion in the 2.0% NaCl model group was significantly increased compared with the vehicle control group (P ⁇ 0.05 or P ⁇ 0.01), and the urinary potassium excretion increased at 60 days.
  • the difference was not statistically significant (P>0.05).
  • the urinary sodium excretion of the rats in the experimental group with 2.0% NaCl/0.1% low-alkali potassium alginate increased at 30 days, but increased significantly at 60 days (P ⁇ 0.01).
  • Excretion of urinary potassium increased significantly at 30 and 60 days (P ⁇ 0.05 or P ⁇ 0.01).
  • the oligomeric potassium alginate After freely drinking the rats in a 5% ratio of potassium alginate (0.1%) solution in a 2% salt solution for 60 days, the oligomeric potassium alginate had no significant effect on the food intake and water intake of the animals, but it was significantly increased.
  • the amount of urine can also significantly reduce the body weight of rats.
  • the effect of hypopolyaluminate potassium on weight loss may be related to the decrease of whole body fluid volume caused by the increase of urine volume.
  • the above-mentioned amount of oligomeric potassium alginate can significantly increase the amount of urinary sodium and urinary potassium excretion, and can significantly increase serum potassium levels, but has no significant effect on fecal sodium and fecal potassium excretion and serum sodium concentration.
  • Potassium oligo-alginate is a milky white or yellow granulated powder, hygroscopic, low in aqueous solution, suitable for development into low-sodium salt for health care, and low-polyaluminum alginate is degraded by using brown algae extract medicinal alginic acid as raw material.
  • a potassium salt of alkydic acid having a low degree of polymerization obtained by salt formation.
  • oligomeric potassium alginate is obtained by extracting from the kelp of the brown algae plant and preparing by a degradation process. The results showed that 100 mg/kg, 250 mg/kg or 500 mg/kg of oligomeric alginate could significantly reduce the blood pressure level of SHRs in spontaneously hypertensive rats after 21 and 28 days of continuous intragastric administration. Similar to 6.5 mg/kg hydrochlorothiazide (equivalent to 3 to 12 times the clinical equivalent).
  • the body's potassium is mainly from food, and most of it is quickly absorbed by the small intestine. Potassium accounts for 5% of the body's inorganic salts and is an essential nutrient for the human body.
  • Clinical studies have shown that urinary potassium excretion in patients with essential hypertension is lower than normal, and moderate potassium supplementation has a hypotensive effect on mild hypertension and some normal blood pressure patients with hypertension, which may be related to potassium. It is related to the regulation of water and body fluid balance. Animal experiments have also shown that an appropriate amount of potassium can reduce blood pressure levels in hypertensive animals.
  • the oligomeric potassium alginate derived from natural algae plants has a small molecular weight and is good for absorption, and has a very significant and sustained antihypertensive effect on SHRs.
  • the mechanism of antihypertensive action may be related to the oligomeric alginic acid itself or low.
  • Molecular alginic acid interacts with potassium ions (eg, oligomeric alginic acid affects the pharmacokinetic properties of potassium ions).
  • low-polyaluminum alginate PA has a dose-related, non-endothelium-dependent relaxation effect on isolated vascular smooth muscle, and its mechanism may be related to inhibition of voltage-dependent calcium channels in vascular smooth muscle cells.
  • the low poly alginate sample is calculated according to the body weight of 60Kg, and the daily service is 2.8g each time.
  • the auxiliary antihypertensive effect can fully meet the national health food requirements.
  • the half-life of the antihypertensive effect is long (up to 144 hours).
  • the oligomeric potassium alginate was prepared according to the method of Example 1; the seaweed oligopeptide was prepared according to the method of Example 2.
  • the low sodium salt in this example consisted of 550 g of NaCl, 160 g of potassium alginate, 60 g of an algal oligopeptide, and 2.9 g of succinic acid.
  • potassium oligomeric alginate was prepared in accordance with the method of Example 1; seaweed oligopeptide was prepared in accordance with the method of Example 2.
  • the low sodium salt of this example contained 71.5% by weight of NaCl, 22% by weight of potassium oligomeric alginate, 6% by weight of algae oligopeptide and 0.5% by weight of yeast hydrolysate (ribose nucleus). Glycosylate).
  • NaCl was milled on an Alpine 160UPZ pin mill running at 500 rpm.
  • the mixed powder was collected in a silo from which a Herzog tablet press was manually supplied in a 50 g portion.
  • the applied pressure is from 0.5 t/cm 2 to 1.0 t/cm 2 (corresponding to a pressure of 50 to 100 MPa).
  • Most of the pellets were pressed at a pressure of 1.0 t/cm 2 .
  • Most pellets are 40 mm in diameter and ⁇ 20 mm in height. The resulting pellets were broken along the diameter.
  • the pellets were further pulverized using a Merz roller mill having a diameter of 200 mm, a roll gap of 3.0 mm, a roll speed of 195 rpm, and 300 rpm.
  • the product was comminuted again on a Merz roller mill (now running at 0.8 mm roll).
  • the comminuted product was sieved on a Mogensen Piccolo equipped with a 200 micron and 710 micron sieve. Fractions were analyzed further to 710 microns and 200 microns 455 microns determined to have a d 50 of low sodium salt.
  • the oligomeric potassium alginate was prepared according to the method of Example 1; the preparation method of the shellfish oligopeptide was as follows:
  • the optimal hydrolysis process for papain hydrolysis Single factor experiments showed that papain hydrolysis was carried out at a temperature of 50 ° C for about 5 h, a substrate concentration of 4%, an enzyme loading of about 5,500 U/g to 10,000 G/g, and a pH of 7.0 to 7.5. The effect is better.
  • Orthogonal test showed that the order of influence of 3 factors was: enzyme amount>substrate concentration>hydrolysis time; the optimal hydrolysis process was: pH value of 7.5 of hydrolysate, and enzyme amount was 5,500 U/g-10,000 G/g, bottom
  • the concentration of the substance is 4%, the temperature is 50 ° C, and the hydrolysis is 6 h. Under this condition, the degree of hydrolysis can reach 37.25%.
  • the enzymatic hydrolyzate with higher hydrolysis degree can be obtained by hydrolysis with papain.
  • the low sodium salt in this example consisted of 500 g of NaCl, 126 g of potassium oligomeric alginate, 45 g of shellfish oligopeptide, and 2.9 g of succinic acid.
  • the specific preparation method is as follows:
  • the product from the Frewitt screen mill was sieved into fractions using 710 micron, 500 micron, 280 micron and 90 micron sieves. Inspection below 90 microns, 90 microns to 280 microns (d 50 is 231 microns), 280 microns to 500 microns (d 50 is 381 microns), 500 microns to 710 microns (d 50 is 587 microns) and above 710 microns Fraction. Further analysis of the fractions from 90 micrometers to 710 micrometers and 445 micrometers d determined to have low sodium salt 50.
  • the oligomeric potassium alginate was prepared according to the method of Example 1; the preparation method of the corn oligopeptide was as follows:
  • the enzymatic hydrolysis of zein by papain took 2 kg of corn protein powder and soaked in 3 liters of water overnight. After gelatinization, the temperature of zein paste was raised from 40 °C to 50 °C, and the dissolution of amino nitrogen increased significantly. When the temperature is further increased, the increase is not obvious and tends to decrease with increasing temperature. This is because proper heating makes the protein structure loose, exposes more enzyme sites, and the enzyme activity also reaches the optimal state. As the temperature continues to increase, the enzyme activity gradually decreases, resulting in a decrease in the amino nitrogen content. Therefore, we chose 50 ° C for the optimum temperature of hydrolysis. The maximum reaction temperature of the enzyme was 60 ° C.
  • the optimal hydrolysis process for papain hydrolysis The single factor test showed that the hydrolysis effect of papain was better when the enzymatic hydrolysis time was about 5 h, the substrate concentration was 4%, the enzyme amount was about 5,500 U/g, and the pH value was 7.0-7.5.
  • the orthogonal experiment showed that the order of influence of the three factors was: enzyme amount>substrate concentration>hydrolysis time; the optimal hydrolysis process was: pH value of 7.8 of hydrolysate, enzyme amount of 5,500 U/g, substrate concentration of 4%.
  • the temperature is 50 ° C, hydrolysis for 6 h, under this condition, the degree of hydrolysis can reach 37.45%.
  • the enzymatic hydrolysate with higher hydrolysis degree can be obtained by hydrolysis with papain.
  • the low sodium salt of this example contains 72% by weight of NaCl containing 20% by weight of oligomeric potassium alginate and 7.5% by weight of corn oligopeptide, and also 0.3% by weight of yeast extract (ribonucleoside) Acid) and 0.2% by weight of magnesium alginate.
  • the oligomeric potassium alginate was prepared according to the method of Example 1; the seaweed oligopeptide was prepared according to the method of Example 2.
  • the low sodium salt in this example consisted of the following mass percent components: NaCl 74.7%, oligomeric potassium alginate 18.4%, seaweed oligopeptide 6.7%, magnesium alginate 0.2%.
  • oligomeric potassium alginate 160 g was oligomeric potassium alginate (d 50 was 258 ⁇ m), sprayed with 120 mL of seaweed oligopeptide solution (58.26 g by dry weight), mixed, and added 650 g of NaCl (d 50 was 39 ⁇ m) and 1.74 g of alginic acid.
  • the remaining NaCl is left for the next preparation of a sample of low sodium salt containing oligomeric potassium alginate and algae oligopeptide.
  • the oligomeric potassium alginate was prepared in accordance with the method of Example 1; the shellfish oligopeptide was prepared in accordance with the method of Example 8.
  • the product from the Frewitt screen mill was sieved into fractions using 710 micron, 500 micron, 280 micron and 90 micron sieves. Further analysis of the fractions 280 micrometers to 710 micrometers (i.e., two fractions were combined), and determined to have a low sodium salt 498 microns 50 d.
  • the oligomeric potassium alginate was prepared according to the method of Example 1; the corn oligopeptide was prepared according to the method of Example 9.
  • the low sodium salt of this example contains 72% by weight of NaCl, 20.5% by weight of oligomeric potassium alginate and 7% by weight of corn oligopeptide, and 0.5% by weight of yeast extract (ribonucleotide). .
  • the oligomeric potassium alginate was prepared according to the method of Example 1; the seaweed oligopeptide was prepared according to the method of Example 2.
  • the product from the Frewitt screen mill was sieved into fractions using 710 micron, 500 micron, 280 micron and 90 micron sieves. Further analysis of the fractions 280 micrometers to 710 micrometers (i.e., two fractions were combined), and determined to have a low sodium salt 498 microns 50 d.
  • the oligomeric potassium alginate was prepared according to the method of Example 1; the seaweed oligopeptide was prepared according to the method of Example 2.
  • the product from the Frewitt screen mill was sieved into fractions using 710 micron, 500 micron, 280 micron and 90 micron sieves. Further analysis of the fractions 280 micrometers to 710 micrometers (i.e., two fractions were combined), and determined to have a low sodium salt 498 microns 50 d.
  • Example 15 boiling drying processing method containing potassium alginate low sodium salt
  • the low sodium salt contains 72% by weight of NaCl, 20.5% by weight of oligomeric potassium alginate and 7% by weight of algae oligopeptide, and 0.4% by weight of yeast extract (ribonucleotide). And 0.1% calcium zinc magnesium minerals.
  • the bottom spray device is composed of a conical material tank and a built-in cylindrical spacer.
  • the bottom of the material tank is equipped with baffles with different diameter distribution holes to separate the air flow inside and outside the circle.
  • the airflow in the spacer is the largest, and the material moves upwards at high speed in the spacer. After entering the expansion chamber, it falls outside the spacer, and the material outside the spacer Move into the spacer and cycle.
  • the liquid atomizing nozzle is installed at the center of the deflector, and the nozzle is sprayed from the bottom to the top, and the direction is consistent with the direction of the sodium chloride fine material and the air flow.
  • the top spray device consists of a conical material tank and an expansion chamber. Since the material tank is conical, the fountain fluidization state in the material tank is ensured, and the inflow air flow pushes the material in the trough upward into the expansion chamber. Since the expansion chamber diameter is larger than the material trough, the inlet air flow rate decreases, and the material is due to itself. When the gravity is greater than the wind, the sodium chloride fine material moves back and forth in the trough and the expansion chamber. There are a plurality of nozzle mounting ports at the top of the expansion chamber for injecting atomized liquid during granulation and coating.
  • the concentration of the potassium alginate seaweed peptide composition is 20% by dry weight, and the temperature of the material containing the yeast hydrolyzate and the calcium zinc magnesium mineral in the potassium alginate seaweed peptide composition is 40 ° C to 60 ° C, 60 ° C to 80 ° C. 80 ° C ⁇ 100 ° C, spray speed 20 ⁇ 25 l / h, 25 ⁇ 35 l / h, 35 ⁇ 40 l / h for screening, the results: potassium alginate seaweed peptide composition material temperature is 40 ° C ⁇ 60 ° C When the temperature of the material is too low, the powder is not easy to dry and is easy to agglomerate.
  • the spraying speed is 20 to 25 liters/hour, the spraying speed is low, the flow rate is small, and the efficiency is affected.
  • the spray speed is 35-40 liters/hour, the spray speed is fast, the powder is not easy to dry completely, and it is easy to agglomerate.
  • the temperature of the material is from 80 ° C to 100 ° C, the temperature of the material is too high, which may cause decomposition of the active ingredients in the intermediate of the composition.
  • the alginate material temperature is 60 ° C ⁇ 80 ° C, the concentration of 20%, the spray speed of 25 ⁇ 35 liter / hour for the diameter of less than 600 microns of sodium chloride fine material 12-25 kg by boiling drying conditions for chlorination
  • the sodium fine material is subjected to functional potassium alginate (sodium) coating granulation.
  • the boiling drying conditions were respectively carried out using a bottom sprayed potassium alginate seaweed peptide composition solution, and the top spray was used for the potassium alginate seaweed peptide composition solution to obtain a good quality d-containing potassium alginate algae peptide having a d 50 of 630 ⁇ m.
  • the granules, the paste of the flavoring agent and the mineral are continuously added, and the mixture is stirred and dried to obtain a sample of the low sodium salt.
  • the systolic blood pressure of SHRs was determined by tail pulse indirect pressure measurement. 40 rats were randomly divided into 4 groups, 10 in each group: blank vehicle control group, potassium alginate low sodium salt, high dose, medium dose and potassium alginate.
  • the low-dose group 500 mg/kg, 250 mg/kg, 100 mg/kg was intragastrically administered daily for 28 days; blood pressure was measured every week, and the blood pressure changes at 3 days and 6 days after stopping the drug were observed.
  • the blood pressure levels of SHRs in the three dose groups of continuous administration for 21 days and low molecular weight potassium alginate decreased (P ⁇ 0.01). When the drug was stopped for 3 days and 6 days, the potassium alginate low sodium salt was high, medium and low.
  • the systolic blood pressure of the three dose groups was lower than that of the vehicle control group at the same time (P ⁇ 0.05 or P ⁇ 0.01).
  • the low sodium salt of 250mg/kg and 500mg/kg potassium alginate could still lower the blood pressure level of SHRs. ⁇ 0.01).
  • the continuous oral administration of potassium alginate low sodium salt can reduce the blood pressure of SHRs in a dose-dependent manner, and it still has a sustained antihypertensive effect at 6 days after stopping the drug. This may be related to the slow elimination of potassium alginate low sodium salt after oral administration.
  • the results of the blood pressure lowering effect test are shown in Table 9.
  • the test population chose spontaneous hypertensive patients.
  • the test population consisted of 30 people in each group.
  • the control group received 35% potassium chloride and low sodium salt as the control group.
  • the daily intake of low-sodium salt containing 35% potassium chloride was 9.0 g, of which sodium chloride was 5.9. Gram, 3.1 grams of potassium chloride.
  • the test group was fed with low sodium salt of low-alcoholic alginate, and 9.0 g of low-sodium salt of low-alcoholic alginate was ingested daily (low-sodium salt of oligomeric sodium alginate prepared by the methods of Examples 6-15, respectively). .
  • One month of feeding, each day was tested for systolic and diastolic blood pressure of each ingestor. The observations are listed in Tables 10-13 below.
  • Example 6 148.97 ⁇ 13.41 142.83 ⁇ 9.50** 6.13 ⁇ 9.35 133.20 ⁇ 11.52*** 15.77 ⁇ 14.90
  • Example 7 148.97 ⁇ 13.48 142.84 ⁇ 9.51** 6.03 ⁇ 9.32 133.30 ⁇ 11.55*** 15.67 ⁇ 14.91
  • Example 8 148.94 ⁇ 13.71 142.82 ⁇ 9.52** 6.12 ⁇ 9.34 133.20 ⁇ 11.58*** 15.84 ⁇ 14.92
  • Example 9 148.92 ⁇ 13.62 142.83 ⁇ 9.52** 6.09 ⁇ 9.31 133.30 ⁇ 11.62*** 15.62 ⁇ 14.90
  • Example 10 148.94 ⁇ 13.26 142.85 ⁇ 9.53** 6.09 ⁇ 9.30 133.30 ⁇ 11.57*** 15.64 ⁇ 14.90
  • Example 11 148.98 ⁇ 13.81 142.82 ⁇ 9.54** 6.16 ⁇ 9.33 133.10 ⁇ 11.61*** 15.88 ⁇ 14.95
  • Example 12 148.93 ⁇ 13.39 142.84 ⁇ 9.54** 6.
  • Example 13 148.98 ⁇ 13.53 142.84 ⁇ 9.52** 6.14 ⁇ 9.33 133.20 ⁇ 11.65*** 15.78 ⁇ 14.90
  • Example 14 148.90 ⁇ 13.21 142.82 ⁇ 9.55** 6.08 ⁇ 9.33 133.30 ⁇ 11.38*** 15.60 ⁇ 14.90
  • Example 15 148.89 ⁇ 13.48 142.81 ⁇ 9.50** 6.08 ⁇ 9.35 133.10 ⁇ 11.46*** 15.79 ⁇ 14.90 Control group 151.77 ⁇ 12.55 151.47 ⁇ 12.79## 0.30 ⁇ 12.74 150.33 ⁇ 13.58## 1.43 ⁇ 13.88
  • Example 6 97.40 ⁇ 9.64 91.27 ⁇ 8.12*** 6.13 ⁇ 8.00 86.57 ⁇ 11.05*** 10.83 ⁇ 10.59
  • Example 7 97.30 ⁇ 9.61 91.23 ⁇ 8.22*** 6.07 ⁇ 8.02 86.56 ⁇ 11.04*** 10.74 ⁇ 10.57
  • Example 8 97.50 ⁇ 9.74 91.17 ⁇ 8.18*** 6.33 ⁇ 7.92 86.58 ⁇ 11.03*** 10.92 ⁇ 10.60
  • Example 9 97.40 ⁇ 9.48 91.25 ⁇ 8.14*** 6.15 ⁇ 7.98 86.54 ⁇ 11.02*** 10.86 ⁇ 10.58
  • Example 10 97.50 ⁇ 9.53 91.49 ⁇ 8.18*** 6.11 ⁇ 8.01 86.59 ⁇ 11.06*** 10.91 ⁇ 10.57
  • Example 11 97.50 ⁇ 9.73 91.29 ⁇ 8.02*** 6.21 ⁇ 8.04 86.56 ⁇ 11.07*** 10.94 ⁇ 10.55
  • Example 12 97.50 ⁇ 9.94 91.46 ⁇ 8.22*** 6.14 ⁇ 8.02 86.54 ⁇
  • Example 6 30 10 15 5 83.33
  • Example 7 30 11 14 5 83.33
  • Example 8 30 12 13 5 83.33
  • Example 9 30 15 10 5 83.33
  • Example 10 30 13 12 5 83.33
  • Example 11 30 12 13 5 83.33
  • Example 12 30 11 14 5 83.33
  • Example 13 30 9 16 5 83.33
  • Example 14 30 13 12 5 83.33
  • Example 15 30 12 13 5 83.33
  • Control group 30 3 4 twenty three 22.33**

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Abstract

一种低钠盐，包括低聚海藻酸钾和氯化钠。该低聚海藻酸钾，其重均分子量为700道尔顿-10,000道尔顿，且所述海藻酸中甘露糖醛酸单元与古罗糖醛酸单元的摩尔比值为0.3-3.3，乌氏黏度为3-16。所述氯化钠与低聚海藻酸盐的重量比为(48-83) :(13-40)。

Description

新型低钠盐的组成、制备和用途
相关申请的交叉引用
本申请主张在2014年09月26日在中国提交的中国专利申请号No.201410505408.4的优先权，其全部内容通过引用包含于此。
技术领域
本申请涉及含低聚海藻酸钾的低钠盐及制备和用途。
背景技术
大家都知道人离不开食盐。食盐的主要成分是氯化钠。氯化钠在人体内以钠离子与氯离子的形态存在。氯化钠摄入过多又会诱发高血压，导致冠心病、脑梗塞、肾功能障碍、视网膜病变等多种疾病，严重影响大家生活质量甚至寿命。据调查我国35-74岁的成年人群中，高血压患病率达27.2％。我国高血压的知晓、治疗与控制状况令人担忧：在现有患者中，自知病情诊断者不足45％，正在服用降压药者不超过30％，仅有不足10％的人血压得到稳定控制。有45％的患者应用减重、限盐、限酒、锻炼等非药物疗法。其中，限盐为最常用方法，补钾是用得最少的。专家指出从以往3次全国高血压调查和研究结果分析与评估表明，虽然我国高血压人群防治成效显著，但患病率和绝对数仍均呈快速增长趋势。
原发性高血压是威胁人类健康的最常见疾病之一，其发病机制尚未完全阐明。研究表明原发性高血压发病机制与个体遗传背景和多种后天环境因素作用所致的血压调节机制失代偿有关，其中主要包括肾素-血管紧张素系统(RAS)的激活、高钠的摄入、胰岛素抵抗及精神神经等因素。
目前，高血压的治疗包括非药物干预和药物治疗两方面。临床上常用的 降压药物主要有六大类：利尿剂、α血受体阻滞剂、钙通道阻滞剂、血管紧张素转换酶(ACE)抑制剂、β抑受体阻滞剂、以及血管紧张素II受体拮抗剂。降压药物的疗效和不良反应情况个体间差异很大。非药物干预主要通过限制食盐的摄入量，合理膳食、减轻体重、运动等方法调节血压，一定程度降低高血压的心血管并发症发生。
健康专家号召人们少吃盐，主要是为了让大家少摄入盐里的钠。现在人们大多吃得咸，而且肉吃得多、菜吃得少。许多包装食品里还暗藏隐形盐，谈起高钠的摄入，80％的钠摄入来自成品食物，这样很容易造成“高钠低钾”的问题，引发高血压等许多疾病。从这个角度来说，低钠盐确实是“健康盐”。低钠盐用钾代替了部分钠，因此能在一定程度上减少钠的摄入，增加钾的摄入，对维持人体钠钾平衡很有帮助。目前，低钠盐，是以碘盐为原料，再添加了一定量的氯化钾和硫酸镁，从而改善体内钠(Na+)、钾(K+)、镁(Mg2+)的平衡状态，预防高血压。现在一些厂家出产了低钠盐，以期望减少氯化钠的摄入量。低钠盐中氯化钠少了，添加氯化钾。有些低钠盐中氯化钾含量竟高达20g/100g-35g/100g。
海藻酸盐在药物制剂上已有应用。海藻酸钾(C6H7O8K)n主要由海藻酸的钾盐组成。海藻酸是由α-α藻酸甘露糖醛酸(M单元)与β-β糖醛古罗糖醛酸(G单元)依靠1，4-糖苷键连接并由不同GGGMMM片段组成的共聚物。G和M酸的浓度(G∶M比率)决定了不同的结构和生物相容性等特性。自然界存在的海藻酸(比如褐藻)中G与M的摩尔比值为0.2至2.5，分子量为100,000道尔顿至1,500,000道尔顿。我国生产的海藻酸盐主要以海带为原料。
US 2009/0104330公开了用于减少食品中的氯化钠的低钠咸味组合物。该组合物含有氯化钠、食物酸和食物酸盐中的至少一种、氨基酸和氨基酸盐中 的至少一种，并可以另外含有氯化钾、酵母提取物、甜味剂和香料。该组合物据说具有降低的金属味/苦味，增强咸味特性和提高咸味的强度。尽管列出了在需要更大或更小粒子的情况下的许多制备该组合物的技术，但可以看出该组合物是通过组分的直接掺合而制备的。由于添加到US 2009/0104330中的氯化钠基产品中的食物酸、氨基酸、酵母提取物、甜味剂和香料添加剂实际上通常具有明显小于氯化钠和氯化钾的粒度，因此，预计如US 2009/0104330中制成的组合物如上解释容易分开，例如在运输和储存时，这产生具有与预期不同的组成的产品，这又影响该组合物的功能。
发明内容
本申请的目的是提供一种含有低聚海藻酸盐的低钠盐。
本申请所提供的低钠盐，含有氯化钠和低聚海藻酸钾，其中，所述低聚海藻酸钾的重均分子量为700道尔顿-10,000道尔顿，乌氏黏度3-16且所述低聚海藻酸钾中甘露糖醛酸单元与古罗糖醛酸单元的摩尔比值为0.3-3.3。
可选的，本申请的低聚海藻酸钾中的所述低聚海藻酸的重均分子量为1,000道尔顿-4,500道尔顿，且所述低聚海藻酸中甘露糖醛酸单元与古罗糖醛酸单元的摩尔比值为0.4-3.3。
通常用于制备上述低聚海藻酸的原料为褐藻。各种褐藻都能作为生产海藻酸的原料，例如海带、水云、萱藻、鹿角菜、马尾藻等。考虑到成本的优化，海带、昆布、巨藻和马尾藻(如半叶马尾藻、亚麻叶马尾藻)中的一种或几种。
本申请提供的制备上述低聚海藻酸的方法包括常规的降解步骤。例如，可选的，所述方法包括将重均分子量为10,000道尔顿-1,500,000道尔顿的海藻酸进行降解，所述降解步骤包括物理降解步骤、光化学降解步骤、固定化酶降解 步骤和化学降解步骤中的一种或几种降解步骤。更进一步，在所述降解步骤之前进行物理降解步骤、光化学降解步骤、固定化酶降解步骤和氧化降解步骤中的一种或几种降解步骤。所述物理降解步骤、光化学降解步骤、固定化酶降解步骤和氧化降解步骤为本领域公知，在PCT/CN99/00202中有详细记载，这里全部引入作为参考。比如物理步骤包括超声波处理或高速剪切处理；光化学步骤是利用光辐射和催化进行处理；氧化降解步骤包括使用有机氧化剂和/或无机氧化剂，如过氧化氢、过氧乙酸、过氧化钾、过氧化碳酸钾、过硼酸钾(钠)、高锰酸钾、过硫酸铵、过硫酸氢钾复盐、亚氯酸钾、亚氯酸钠等；固定化酶降解步骤包括使用多孔钠玻璃球载体固定藻酸分解酶后，装柱分解。
所述低聚海藻酸钾是上述低聚海藻酸与碱性的钾离子中和反应获得的。所述低聚海藻酸钠是上述低聚海藻酸与碱性的钠离子中和反应获得的。
本申请提供一种含海藻酸钾的低钠盐，包括所述的低聚海藻酸钾和氯化钠。
所述氯化钠与低聚海藻酸钾的重量比为(48-83)∶(13-40)。
在本申请的一个技术方案中，所述低钠盐中还包括低聚肽。
所述低聚肽为海藻低聚肽、玉米低聚肽或贝类低聚肽。
所述氯化钠、低聚海藻酸钾和低聚肽的质量比为(48-83)∶(13-40)∶(3.8-11.5)。
所述低钠盐中还包括添加剂，所述添加剂选自味道改进剂、味道掩蔽剂、矿物质、抗结块剂或流动添加剂，味道改进剂、味道掩蔽剂、矿物质、抗结块剂和流动添加剂中的一种或两种以上任意组合；所述氯化钠、低聚海藻酸钾、低聚肽和添加剂重量比为(48-83)∶(13-40)∶(3.8-11.5)∶(0.2-0.5)。
所述添加剂占含海藻酸盐低钠盐总重量的0.2％-0.5％。
所述味道掩蔽剂选自下述物质：食用有机酸；氨基酸及其衍生物；酵母；酵母提取物；来自酵母提取物之类来源的水解蛋白；肽；水解植物蛋白；水解脂肪；核糖核苷酸；类黄酮；氨基酸与二羧酸的酰胺；海藻糖和葡萄糖酸盐中的一种或者两种以上任意组合；或它们的组合；
所述味道改进剂选自下述物质中的一种或两种以上任意组合：衍生自多香果、罗勒、辣椒、桂皮、丁香、小茴香、莳萝、大蒜、马郁兰、肉豆蔻、红辣椒、黑胡椒、迷迭香和姜黄中的任一种的香料油性树脂和油；精油；柑橘油；蒜味香料；植物提取物；蛋白质水解产物；天然和人造的混合香料，和通过还原糖与蛋白质衍生组分之间的美拉德型反应制成的加工香料；所述矿物质(微量元素)钙、镁、锌、铬、铁、钼、铜、锰均以海藻酸盐的形式加入。
所述低钠盐是具有250微米至1毫米的粒径的颗粒。
所述低钠盐的制备方法包括使用大于150微米的低聚海藻酸钾黏附50微米粒度以下的食盐粉末造粒或再使用40MPa至100MPa的压力压制后粉碎获具有250微米至1毫米的粒径的低钠盐颗粒。
本申请还提供了制备所述低聚海藻酸盐的方法，该方法包括按照上述的方法制备低聚海藻酸，然后制成含低聚海藻酸钾(钠)的低钠盐。
本申请提供的一种低钠盐的制备方法，包括下述步骤：按照所述的组分质量比，使用粒度大于150微米的低聚海藻酸钾黏附粒度为50微米以下的氯化钠粉末造粒或使用粒度大于150微米的低聚海藻酸钾黏附粒度为50微米以下的氯化钠粉末造粒再使用40MPa至100MPa的压力压制后粉碎获具有250微米至1毫米的粒度的低钠盐颗粒。
在本申请的一个技术方案中，本申请的种低钠盐的制备方法，包括下述步骤：按照所述组分比例，在d50为258微米-270微米的低聚海藻酸盐粉中喷洒 低聚肽溶液，混合后加入d50为39微米-50微米的NaCl粉，在造粒机上造粒，干燥，使用280微米的筛，过筛得到含低聚海藻酸钾及低聚肽的低钠盐，并确定具有498微米-640微米的d50；余留下NaCl供下一次制备含低聚海藻酸钾及低聚肽的低钠盐样品用。
在本申请的一个技术方案中，低钠盐的制备方法，包括下述步骤：按照所述组分比例，在d50为258微米-270微米低聚海藻酸钾粉中喷洒低聚肽溶液后混合，加入d50为39微米-50微米的NaCl粉，在造粒机上造粒，将得到的混合物在Herzog压片机上使用40MPa至100MPa的压力制造丸片；然后将所得丸片沿直径破碎，并在筛磨机研磨筛分得到具有398微米-520微米的d50的低钠盐颗粒。
在本申请的一个技术方案中，低钠盐的制备方法，包括下述步骤：按照所述的重量份数比，将低聚海藻酸盐和低聚肽和除氯化钠以外的其余组分混合制备成干重计为20％的低聚海藻酸盐和低聚肽的组合物溶液，按照低聚海藻酸盐和低聚肽的组合物溶液温度为60℃～80℃、喷液速度25～35升/小时，为直径小于600微米的氯化钠细粒物料12千克-25千克通过沸腾干燥对氯化钠细粒物料进行包衣得到含低聚海藻酸盐和低聚肽的d50为630微米低钠盐样品；所述沸腾干燥条件采用底喷低聚海藻酸盐和低聚肽的组合物溶液或者顶喷用于低聚海藻酸盐和低聚肽的组合物溶液。
上述低钠盐在制备预防或辅助治疗高血压的产品中的应用也在本申请的保护范围中。
本申请提供了一种预防或辅助治疗高血压的方法，包含对受试者施用上述低聚海藻酸钾。
根据本申请的一个实施方式，其中所述低聚海藻酸钾每日摄入量为2.8克 /60kg。
本申请还提供了一种预防或辅助治疗高血压的方法，包含对受试者施用上述低钠盐。
本申请通过实验证明，口服氯化钾，是因为钾离子有利尿作用，使一部分钠离子经肾脏排出体外，低聚海藻酸钾的钾离子与氯化钾的钾离子具有同样的利尿效果，低聚海藻酸有吸收小肠液、大肠液中的钠离子的作用，这是氯化钾不具有的。
经试验表明，低聚(低分子)海藻酸钾不仅具有补钾排钠作用，因低聚(低分子)海藻酸钾中含有小分子海藻酸钾，在肠道其小分子海藻酸转化成小分子海藻酸钠可以经肠粘膜吸收进入血管，小分子海藻酸钠具有钙离子通道阻滞剂作用，使血压下降。低聚海藻酸钾对饮用高盐溶液大鼠的影响(见实施例)，观察低聚海藻酸钾对大鼠自由饮用按照2％盐溶液加5％比例的低聚海藻酸钾(0.1％)溶液60天后，低聚海藻酸钾对动物摄食量和饮水量未见明显影响，但可非常明显增加尿量而同时明显减轻大鼠体重，低聚海藻酸钾减轻体重的作用可能与尿量增加所致的全身体液量降低有关。此外，上述用量的低聚海藻酸钾可显著增加尿钠和尿钾排泄量，同时可显著增加血钾水平，而对粪钠和粪钾排泄及血清钠浓度未见明显影响。确认低聚海藻酸钾在体内能起补钾排钠作用。
低聚海藻酸钾降压机制至少与受试品的利尿和增加尿、粪便钠排泄量的作用有关。低聚海藻酸钾适用于需要补钾及有心脑血管疾病倾向的人群。
大生产规模的低聚海藻酸钾样品按人体体重60Kg计算，日服1次，每次2.8克，辅助降血压效果完全可以达到国家保健食品要求的标准。降压功效半衰期较长(可达144小时)，大规模生产的低聚海藻酸钾添加到各类食品中(如： 食盐，奶制品，调味品等)，日服用量以食盐计不大于6.0克。含低聚海藻酸钾的低钠盐添加低聚肽后可以增加鲜味，使低钠盐成为咸鲜的调味品，会更受消费者的欢迎。
当食物经口腔、胃初步消化后，通过胃的运动被排空进小肠。在小肠，胃酸被胰液中的碳酸氢钠中和，为小肠的各种酶的作用提供了适宜的碱性环境。如胰淀粉酶在pH值为6.9-7.0时活性最大；胰蛋白酶在pH值为8时活性最大。所以在小肠里，食物得到了彻底的分解，蛋白质、淀粉、脂肪被分解为氨基酸、葡萄糖、脂肪酸和甘油。
海藻酸钾经口服进入胃中，胃液pH值是1-3.5海藻酸钾与胃酸作用，形成凝胶，钾离子大部分由小肠迅速吸收进入血管，海藻酸经胃进入小肠后，胰液中的碳酸氢钠构成小肠液的一部分，小肠液pH值是7.8-8.0。大肠液pH值为8.3～8.4，海藻酸与肠液中碱性的碳酸氢钠作用，转化成海藻酸钠，经过结肠、直肠吸收水分，在直肠海藻酸转化成的海藻酸钠成为粪便的一部分，被排出体外，实现了补钾排纳。
具体实施方式
下述实施方式或实施例中的百分含量如无特别说明均为重量百分含量。
本申请的目的是提供一种含有低聚海藻酸钾的低钠盐。
本申请所提供的低钠盐，含有氯化钠和低聚海藻酸钾，其中，所述低聚海藻酸钾的重均分子量为700道尔顿-10,000道尔顿，乌氏黏度3-16且所述海藻酸中甘露糖醛酸单元与古罗糖醛酸单元的摩尔比值为0.3-3.3。
可选的，本申请的低聚海藻酸钾中的所述低聚海藻酸的重均分子量为1,000道尔顿-4,500道尔顿，且所述低聚海藻酸中甘露糖醛酸单元与古罗糖醛酸单元的摩尔比值为0.4-3.3。
本申请提供的制备上述低聚海藻酸的方法包括常规的降解步骤。例如，可选的，所述方法包括将重均分子量为10,000道尔顿-1,500,000道尔顿的海藻酸进行降解，所述降解步骤包括物理降解步骤、光化学降解步骤、固定化酶降解步骤和化学降解步骤中的一种或几种降解步骤。更进一步，在所述降解步骤之前进行物理降解步骤、光化学降解步骤、固定化酶降解步骤和氧化降解步骤中的一种或几种降解步骤。所述物理降解步骤、光化学降解步骤、固定化酶降解步骤和氧化降解步骤为本领域公知，在PCT/CN99/00202中有详细记载，这里全部引入作为参考。比如物理步骤包括超声波处理或高速剪切处理；光化学步骤是利用光辐射和催化进行处理；氧化降解步骤包括使用有机氧化剂和/或无机氧化剂，如过氧化氢、过氧乙酸、过氧化钾、过氧化碳酸钾、过硼酸钾(钠)、高锰酸钾、过硫酸铵、过硫酸氢钾复盐、亚氯酸钾、亚氯酸钠等；固定化酶降解步骤包括使用多孔钠玻璃球载体固定藻酸分解酶后，装柱分解。
本申请中低聚海藻酸钾是低聚海藻酸的钾盐低聚海藻酸的重均分子量以及甘露糖醛酸单元(M)与古罗糖醛酸单元(G)的摩尔比值可以用本领域常用的方法测定，比如，使海藻酸降解所得的低聚海藻酸产物与碱性物质反应(例如氢氧化钠)，得到低聚海藻酸的可溶性盐，利用美国Wyatt公司(WTC)的mini DAWN TREOS激光光散射仪与美国Waters公司的150c、PL220c及ALLIANCE 2000按照使用说明书，测定得到低聚海藻酸的分子量及分子量分布，并计算出重均分子量。测定甘露糖醛酸单元与古罗糖醛酸单元的摩尔比值可采用化学法，对样品进行酸水解，使成单一的甘露糖醛酸单元及古罗糖醛酸 单元的混合物，利用阴离子交换树脂吸附，洗脱，可将甘露糖醛酸单元及古罗糖醛酸单元的混合物分开，经显色，分别测甘露糖醛酸单元及古罗糖醛酸单元485nm下总的吸光度值，通过计算可以得到G与M的摩尔比值。也可以用核磁共振法(NMR)测定海藻酸中G，M，GG，MM，GM中单体的含量。
上述分子量测定的方法为粘度法。粘度法测定分子量，所需设备较简单，操作较易掌握，如测乌氏粘度，常用于多糖的分子量测定。粘度法分子量测定，先是测定样品特性粘度η，然后通过换算方程，即经验式η＝KMa计算分子量。乌氏粘度计：毛细管长度为140nm±5nm，内径0.5nm±0.05nm，B球容积为3.35mL±0.5mL，在25℃，用蒸馏水测定流出时间应在120秒～180秒间。用秒表准确测定溶液的流出时间。读取每个浓度(C1，C2，C3...)的流出时间，测试时的温度一般采用25℃±0.05℃的恒温水浴。低聚海藻酸钾就是采用乌氏粘度计测粘度来控制平均分子量。海藻酸钾在1％的蒸馏水溶液中的pH值约为7.3。聚合度(DP)和分子量与海藻酸钾溶液的粘性直接相关。
所述低聚海藻酸钾是上述低聚海藻酸用含钾的碱性化合物中和反应得到。
在一个可选的方案中，本申请的低钠盐中的氯化钠与低聚海藻酸钾的重量比为(48-83)∶(13-40)；如具体的范围还可以为(64-77)∶(15-22)，(64.6-76.9)∶(15.38-22)。具体的，所述氯化钠占所述低钠盐总重量的48％-83％，具体的可以为64.6％-76.9％。所述低聚海藻酸钾占所述低钠盐总重量的13％-40％；具体的可以为15.38％-22％。
所述含氯化钠的材料可来自数种不同的来源，例如海盐、岩盐、精制(真空)盐或合成盐来源。
所述低钠盐中还包括添加剂，所述添加剂选自味道改进剂、味道掩蔽剂、矿物质、抗结块剂或流动添加剂，味道改进剂、味道掩蔽剂、矿物质、抗结块 剂和流动添加剂中的一种或两种以上任意组合；所述添加剂占含海藻酸盐低钠盐总重量的0.2％-0.5％。
所述氯化钠、低聚海藻酸钾、低聚肽和添加剂重量比为(48-83)∶(13-40)∶(3.8-11.5)∶(0.2-0.5)。具体的重量比可以为(64-77)∶(15-22)∶(5-8)∶(0.2-0.5)，还可以为(64.6-76.9)∶(15.38-22)∶(5.8-7.76)∶(0.2-0.5)。
在本申请中，低钠盐产品被定义为既包括下述产品：其中一部分氯化钠被低聚海藻酸钾代替(在本文中也称作氯化钠替代材料，例如低聚海藻酸钾)替代(在这种实施方案中，含有氯化钠和氯化钠替代材料的材料被称作“含氯化钠的材料”)的产品；该产品同时可含有至少一种添加剂(例如增味剂、掩味剂、营养素或任何其它添加剂)的产品；又包括下述产品：通过添加充当所谓增味剂的添加剂来产生强盐味感觉、以确保用较低量的氯化钠体验到相同味道效果的基于氯化钠的产品；以及上两种产品的组合。基本干燥在本申请中是指基于(总)固体，具有低于3重量％、典型的低于1重量％的游离水含量。游离水是指在100℃可以(从粒子中)蒸发的任何水。
本申请的低钠盐还可包括添加剂，所述添加剂在一个实施方案中选自抑制、增强、影响或改变味道和/或风味的材料，或影响该盐产品或可以使用本申请盐产品的食品的结块性质、自由流动性质、颜色、质地、微生物稳定性、气味或营养价值的材料。所述添加剂可以为合成的添加剂例如为源自天然来源的合成添加剂。
在典型的的实施方案中，该添加剂是味道/风味增强剂(味道改进剂)、味道/风味掩蔽剂(例如掩蔽氯化钠替代材料的令人不愉快的味道(苦味或金属味))、抗结块剂或流动添加剂。在更典型的的实施方案中，该添加剂是味 道/风味增强剂或味道/风味掩蔽剂。由于这两类味道增强和味道掩蔽剂常常重叠，在本文中它们简单地统称为“增味剂”。
增味剂可选自本领域技术人员已知的材料。适合作为增味剂的材料的实例可见于例如WO 2004/075663。
在一个实施方案中，上述味道/风味增强剂或味道/风味掩蔽剂可以选自由下述物质组成的组：食用有机酸，例如琥珀酸、柠檬酸；氨基酸及其衍生物，例如谷氨酸盐/酯；酵母；酵母提取物；来自酵母提取物之类来源的水解蛋白；肽；水解植物蛋白；水解脂肪；核糖核苷酸；类黄酮；氨基酸与二羧酸的酰胺；海藻糖；葡萄糖酸盐；其它调味剂或风味调节物质；或它们的组合。其它实例包括有机酸，例如乳酸、苹果酸；有机酸的盐；核糖核苷酸的盐；来自美拉德反应的产品和发酵食品，例如豆酱、鱼酱、沙丁鱼和奶酪。
所述调味剂是本领域技术人员已知的，术语调味剂包括衍生自多香果、罗勒、辣椒、桂皮、丁香、小茴香、莳萝、大蒜、马郁兰、肉豆蔻、红辣椒、黑胡椒、迷迭香和姜黄中的任一种的香料油性树脂和油；精油，包括茴香油、香菜油、丁香油、桉叶油、茴香油、大蒜油、生姜油、薄荷油、洋葱油、花椒油、迷迭香油和薄荷油；柑橘油，例如橙油、柠檬油、苦橙油和陈皮油；蒜味香料，包括大蒜、韭菜、细香葱和洋葱；植物提取物，包括山金车花提取物、洋甘菊花提取物、啤酒花提取物和金盏花提取物；植物香料提取物，包括黑莓、菊苣根、可可、咖啡、可乐、甘草、蔷薇果、sassaparilla root、洋檫木树皮、罗望子、甘草和香草提取物；蛋白质水解产物，包括水解植物蛋白(HVPs)、肉蛋白水解产物、乳蛋白水解产物；天然和人造的混合香料，和通过还原糖与蛋白质衍生组分(包括氨基酸)之间的美拉德型反应制成的加工(反应)香料。
代表性的独立调味剂包括苯甲醛、二乙酰基(2，2-丁二酮)、香草醛、乙基香草醛和柠檬醛(3，7-二甲基-2，6-辛二烯醛)中的一种或两种以上任意组合。
在一个实施方案中，可以在该盐产品中加入另外的添加剂。在一个典型的实施方案中，此类另外的添加剂可以选自由维生素、酸、酵母、氨基酸、功能添加剂或营养素例如氟化物、碘化物、碘酸盐、矿物质、亚硝酸盐、硝酸盐、调味剂、香料、糖、(天然)调味料、香料或香草。
在本申请的一个技术方案中，本申请低钠盐含有氯化钠(NaCl)、低聚海藻酸钾和低聚肽；所述低聚肽为海藻低聚肽，贝类低聚肽或玉米低聚肽或他们的任意组合。所述氯化钠、低聚海藻酸钾和低聚肽的重量比为(48-83)∶(13-40)∶(3.8-11.5)；具体的重量比可以为(64-77)∶(15-22)∶(5-8)，还可以为(64.6-76.9)∶(15.38-22)∶(5.8-7.76)。具体的，所述低聚肽可以占所述低钠盐总重量的3.8％-11.5％。
上述低聚肽是天然蛋白的酶解产物，其中，海藻低聚肽为海藻蛋白的酶解产物，贝类低聚肽为贝类蛋白的酶解产物，玉米低聚肽是玉米蛋白的酶解产物。海藻及贝类低聚肽。低聚肽可以增加鲜味，还有辅助降血压作用。
另外，由于添加到氯化钠基产品中的添加剂具有比氯化钠原材料小的粒度，在它们涉及除低聚海藻酸钾以外有机添加剂时尤为如此。例如，酵母基添加剂具有远低于100微米的粒度，而工业上可得的氯化钠通常具有数百微米的粒度。如果混合这两种材料，在运输和储存时会发生分离。附聚是避免这种分层的方式。但是，在压制和粉碎至所需粒度后，较小粒子会出现在粒子外表面上，从而造成添加剂损失。
此外，由于许多添加剂具有与氯化钠和氯化钠替代材料不同的性质，因此，从加工角度看，更好的是避免它们大部分位于最终产品的外表面上。例如，低 聚海藻酸钾比氯化钠吸湿，以致盐产品在添加剂粒子位于外表面上时表现出比它们包埋和均匀混合在整个盐产品中时更吸湿的性质。因此，本申请的一个技术方案是找出更有效、并产生没有上述缺点的均匀低钠盐产品的改进的方法。我们现在已经发现更有效、并产生具有改进的味道的低钠盐产品的改进的方法，其中添加剂与氯化钠和任选氯化钠替代材料均匀混合并包含在个体颗粒中。本申请的方法通过低聚海藻酸钾添加低聚肽的组合物涂敷在氯化钠细粒的表面便可以提高抗吸湿的特性。
本申请的低钠盐产品例如由自由流动的粒子构成。如粉碎步骤包括降低粒子粒度的任何方法，并包括例如破碎、压碎或研磨之类的方法。
应该指出，组分可以是其中两种或更多种一起在一个综合步骤中粉碎，或通过单独粉碎步骤粉碎。如果在该方法中使用氯化钠替代材料，其可以与氯化钠一起粉碎或单独粉碎。
压制步骤包括通过施加外力而使粒子附聚的任何方法，用于压制粒子混合物的压力是在丸片的单向压制中施加的压力(造成压制的粒子混合物的一定密度)。但是，可以合适地通过其它压制机(例如轧辊压制机)进行压制。在这些情况下，所用压力是造成与单向压制中相同的压实体密度的压力。压制步骤包括通过施加外力而使粒子附聚的任何方法，例如通过在40MPa至100MPa的压力下进行施加外力而使粒子附聚。
本申请方法在一个实施方案中可含有后继步骤，其中筛分材料以分离出所需组成的粒子，或将所需粒度范围的粒子。
具体的，低钠盐产品具有250微米至1毫米的粒度，使用大于150微米的低聚海藻酸钾黏附50微米粒度以下的食盐粉末造粒或再使用40MPa至100 MPa的压力压制后粉碎获低聚海藻酸钾与食盐粒子混合物；以产生具有250微米至1毫米的所需粒度的粒子；其中在基本干燥的条件下进行这些步骤。
通过该方法获得的产品实际上以添加剂更均匀混入含氯化钠的粒子中为特征，并且还具有良好的抗分离性和抗磨性。
在本申请的一个实施方式中，将低聚海藻酸钾粉(d50为258微米-270微米)喷洒海藻低聚肽溶液，混合后加入NaCl粉(d50为39微米-50微米，在造粒机上造粒，干燥，使用280微米的筛，过筛得到含低聚海藻酸钾及海藻低聚肽的低钠盐。并确定具有498微米-640微米的d50。余留下NaCl供下一次制备含低聚海藻酸钾及海藻低聚肽的低钠盐样品用。
在本申请的另一个实施方式中，将低聚海藻酸钾粉(d50为258微米-270微米)喷洒海藻低聚肽溶液后混合，加入NaCl粉(d50为39微米-50微米，在造粒机上造粒，由这种混合物在Herzog压片机上使用1.0t/cm2压力(相当于100MPa的压力)制造50克丸片(40毫米直径，20毫米高度)。将所得丸片沿直径破碎，并在Frewitt筛磨机上使用6毫米、3毫米和最后1毫米的筛研磨。使用710微米、500微米、280微米和90微米的筛将来自该Frewitt筛磨机的产品筛分成级分。进一步分析级分280微米至710微米(即合并两个级分)并确定具有398微米-520微米的d50。
在本申请的一个实施方式中，将低聚海藻酸钾和低聚肽和除氯化钠以外的其余组分混合制备成干重计为20％的低聚海藻酸钾和低聚肽的组合物溶液，按低聚海藻酸钾和低聚肽的组合物溶液物料温度为40℃～60℃、60℃～80℃、80℃～100℃，喷液速度20～25升/小时、25～35升/小时、35～40升/小时进行筛选，结果：低聚海藻酸钾和低聚肽的组合物溶液物料温度为40℃～60℃时，物料温度过低，粉粒不易干燥，易结块。喷液速度为20～25升/小时，喷 液速度低，流量小，影响效率。喷液速度为35～40升/小时，喷液速度快，粉粒不易干燥完全，易结块。物料温度为80℃～100℃时，物料温度过高，可能会引起组合物中间体中有效成分的分解。故选择低聚海藻酸钾和低聚肽的组合物溶液物料温度为60℃～80℃、浓度20％，喷液速度25～35升/小时为直径小于600微米的氯化钠细粒物料12千克-25千克通过沸腾干燥条件对氯化钠细粒物料进行功能性海藻酸钾包衣制粒。沸腾干燥条件分别采用了底喷海藻酸钾海藻肽组合物液，顶喷海藻酸钾海藻肽组合物液均可得到品质稳定的含低聚海藻酸钾海藻肽的d50为630微米低钠盐样品。其氯化钠、低聚海藻酸钾和低聚肽的重量比为(48-83)∶(13-40)∶(3.8-11.5)。具体的重量比可以为(64-77)∶(15-22)∶(5-8)，还可以为(64.6-76.9)∶(15.38-22)∶(5.8-7.76)。
本申请中上述海藻低聚肽的制备如下：采用酶水解法、外源酶技术。
蛋白质酶解工程是由肽链内切酶和肽链外切酶共同完成的。前者的水解产物为多肽，后者的水解产物为游离氨基酸，所以靠添加内切酶或者再添加外切酶提高水解能力，不同的水解原料中的蛋白质种类和氨基酸构成比例各不相同，因此酶的选择和酶的水解条件也有明显的差异，外源酶技术可以分为单一酶解技术、双酶酶解技术和多酶复合酶解技术。
(1)单酶酶解技术单酶法是只用一种外源酶对原料中的蛋白质进行水解获得水解蛋白的方法。采用正交法优化各水解条件，确定了枯草杆菌中性蛋白酶为最佳，水解度60％-62.6％。
(2)双酶酶解技术单一酶对蛋白质的水解总是有限的，因此若选用对蛋白质底物酶解特异性有互补作用的两种酶，可以获得较好的水解效果。利用枯草杆菌中性蛋白酶和胃蛋白酶两种外源酶水解海藻裙带菜，水解率可达68.0％。
利用木瓜白酶和碱性蛋白酶两种水解海藻海带菜，水解率可达69.0％。
(3)多酶复合酶解技术多酶复合法是用两种以上的酶对原料蛋白质进行水解的方法。采用多酶复合酶解技术，先用混合内肽酶进行短时间水解，使蛋白质水解成肽段、结构变松散后升温灭酶，再添加风味蛋白酶(Flavourzyme)在其适宜条件下进行第二阶段酶解，水解度可达68.2％，而且水解液具有独特的鲜美风味。多酶法可利用多种蛋白酶的作用专一性使原料蛋白质充分水解成氨基酸和端肽，产生的呈味氨基酸和肽会使水解液的味道更加鲜美。
水解时间对海藻水解率的影响
固定水解温度调到50℃，在其他因素不变时，控制不同水解时间，以水解时间为横坐标，样品液中氨基酸含量为纵坐标，结果可以看出，水解时间在2小时～4小时范围内水解情况不明显，水解率升高缓慢。随着水解时间的延长，氨基酸量逐渐积累，当水解时间达到4小时后水解率快速地升高，到6小时后升高速度有所减缓。一定时间后，氨基酸浓度积累至较大浓度，再继续水解，氨基酸的含量增加甚微，这可能是新生成的氨基酸较少，已产生的氨基酸随着时间的延长更易发生二次变化，从而减少了水解液中的氨基酸，同时也发生美拉德反应，也消耗了产品中的氨基酸，使产品中的氨基酸含量下降。通过感官评定发现水解5、6小时的水解液在颜色和香气方面更优于其他几组，综合各方面因素考虑，当氨基酸积累至最大浓度时，应停止水解，避免发生副反应，但时间过长会影响产品的感官品质。可确定水解时间控制在6小时比较适宜。利用超声波预处理酶解底物，水解效率能得到显著提高。
更进一步的，本申请还提供了上述低钠盐在预防高血压或者制备预防高血压的产品或者食品中的应用。
自1998年起大连雅威特生物技术股份有限公司使用常用的工艺技术，如热降解法、氧化法、超声降解法、酸降解法，藻酸裂解酶法单独使用或组合使用将分子量大的海藻酸降解成分子量小的低聚海藻酸，然后用含钾的碱中和得到低聚海藻酸钾。经过10年的努力使制备低聚海藻酸钾的工艺技术日臻成熟，10年来通过药效学实验发现在保持降压有效率的条件下，随着海藻酸钾样品的乌氏粘度下降，给自发高血压大鼠饲喂的海藻酸钾的量减少，大连雅威特生物技术股份有限公司研制的低聚海藻酸钾乌氏黏度为3-16。多项动物试验，证明低聚海藻酸钾确实具有补钾排钠的作用，其效果远远好于氯化钾。
本申请通过实验证明，口服氯化钾，是因为钾离子有利尿作用，使一部分钠离子经肾脏排出体外，海藻酸钾的钾离子与氯化钾的钾离子具有同样的利尿效果，海藻酸有吸收小肠液、大肠液中的钠离子的作用，这是氯化钾不具有的。
经试验表明，低聚(低分子)海藻酸钾不仅具有补钾排钠作用，因低聚(低分子)海藻酸钾中含有小分子海藻酸钾，在肠道其小分子海藻酸转化成小分子海藻酸钠可以经肠粘膜吸收进入血管，小分子海藻酸钠具有钙离子通道阻滞剂作用，使血压下降。低聚海藻酸钾对饮用高盐溶液大鼠的影响(见实施例)，观察低聚海藻酸钾对大鼠自由饮用按照2％盐溶液加5％比例的低聚海藻酸钾(0.1％)溶液60天后，低聚海藻酸钾对动物摄食量和饮水量未见明显影响，但可非常明显增加尿量而同时明显减轻大鼠体重，低聚海藻酸钾减轻体重的作用可能与尿量增加所致的全身体液量降低有关。此外，上述用量的低聚海藻酸钾可显著增加尿钠和尿钾排泄量，同时可显著增加血钾水平，而对粪钠和粪钾排泄及血清钠浓度未见明显影响。确认低聚海藻酸钾在体内能起补钾排钠作用。
低聚海藻酸钾降压机制至少与受试品的利尿和增加尿、粪便钠排泄量的作用有关。低聚海藻酸钾适用于需要补钾及有心脑血管疾病倾向的人群。
大生产规模的低聚海藻酸钾样品按人体体重60Kg计算，日服1次，每次2.8克，辅助降血压效果完全可以达到国家保健食品要求的标准。降压功效半衰期较长(可达144小时)，大规模生产的低聚海藻酸钾添加到各类食品中(如：食盐，奶制品，调味品等)，日服用量以氯化钠计6.0克。含海藻酸钾的低钠盐添加海藻低聚肽后可以增加鲜味，使低钠盐成为咸鲜的调味品，会更受消费者的欢迎。
当食物经口腔、胃初步消化后，通过胃的运动被排空进小肠。在小肠，胃酸被胰液中的碳酸氢钠中和，为小肠的各种酶的作用提供了适宜的碱性环境。如胰淀粉酶在pH值为6.9～7.0时活性最大；胰蛋白酶在pH值为8时活性最大。所以在小肠里，食物得到了彻底的分解，蛋白质、淀粉、脂肪被分解为氨基酸、葡萄糖、脂肪酸和甘油。
海藻酸钾经口服进入胃中，胃液pH值是1-3.5海藻酸钾与胃酸作用，形成凝胶，钾离子大部分由小肠迅速吸收进入血管，海藻酸经胃进入小肠后，胰液中的碳酸氢钠构成小腸液的一部分，小肠液pH值是7.8-8.0。大肠液pH值为8.3～8.4，海藻酸与肠液中碱性的碳酸氢钠作用，转化成海藻酸钠，经过结肠、直肠吸收水分，在直肠海藻酸转化成的海藻酸钠成为粪便的一部分，被排出体外，实现了补钾排纳。对于不适宜海藻酸钾的慢性肾功能衰竭的人群，采用低聚海藻酸钠辅助降压是适宜的选择。
实施例
实施例1、低聚海藻酸钾的制备
低聚海藻酸钾以海藻酸钠为原料，在乙醇中用盐酸酸化后将海藻酸钠转化成海藻酸，分离出酸性乙醇后再用水做溶剂，用氢氧化钾做pH值调节剂，将海藻酸转化成海藻酸的钾盐，其化学反应如下：
C5H7O4COONa+HCl＝C5H7O4COOH+NaCl
C5H7O4COOH+KOH＝C5H7O4COOK+H2O
1.生产工艺过程：
1)海藻酸钠前处理(转化反应)；2)降解成盐；3)精制纯化；4)蒸发浓缩；5)干燥制粒(低聚海藻酸钾)。
2.投料配比
海藻酸钠∶乙醇∶盐酸＝1.0∶1.5∶0.5
海藻酸∶配料水∶过氧化氢∶氢氧化钾∶活性炭＝1.0∶6.0∶0.4∶0.4∶0.1
3.工艺技术条件
a转化反应：浸泡时间10h-12h；
b降解反应：温度＝85℃±8℃，时间＝90min～120min；
c成盐反应：氢氧化钾溶液浓度＝35％～40％，反应温度≤反应℃；
4.质量要求
a降解反应物粘度(乌氏粘度)≤20；
b成盐反应物的pH值＝7.5～8.0；
5.操作方法
a.转化：投料时，先加入乙醇后再启动搅拌器，然后加入海藻酸钠再按要求加入盐酸充分搅拌均匀后浸泡10小时-12小时，将酸性乙醇分离出来。
b.降解：投料时先加入5倍于海藻酸的蒸馏水，再加入3％浓度的过氧化氢，启动搅拌器，再加入海藻酸，同时向反应釜夹层内通入蒸汽加温，直到反 应物的温度达到规定的温度时，开始计时进行降解处理，保持规定的反应温度和时间后取样检验，反应物的粘数动搅小于乌氏粘度20，降解处理完成。
c.成盐：降解处理结束后，向反应釜夹层内通入冷却水，使反应物的温度，降到成盐温度的要求时，便可向反应物内缓缓加入pH调节液，进行成盐反应，反应过程中随时测反应物的pH值，直到pH值达稳定的7.5～8.0时停止加碱，加入藻酸裂解酶，按海藻酸钾干重计，每10公斤加入藻酸裂解酶液10升。藻酸裂解酶的比活力为1800U/MG裂解温度控制在40℃，反应5小时。
d.脱味脱色：按成盐后的海藻酸钾溶液的体积(L)量，加入1％的活性炭，在搅拌的条件下加温至60℃～70℃保持60分钟，即可放料送下道工序。
e.精制纯化
上道工序所得海藻酸钾的水溶液，在反应过程中生成的不溶性多价金属藻酸盐(如，Ca、Fe、Pb工序等)以及海藻纤维，活性炭等杂物，应通过过滤的方法而分离除去，从而获得较纯净的海藻酸钾溶液。
f.蒸发浓缩
精制纯化过程所得到的海藻酸钾水溶液进行浓缩处理，而使溶液的固形物提高。选用设备真空蒸发器(JMZ200)蒸发浓缩温度：50℃～70℃；浓缩液浓度：≥20％；具体操作方法为：
(a)检查使用设备是否运转正常，一切无误后，先将设备进行预热处理，然后再按规定条件进料进行浓缩操作。
(b)按所用设备的使用说明及注意事项进行操作，将滤液浓缩到浓度：≥20％浓度后送下道工序备用。
g.干燥制粒
将浓缩的海藻酸钾溶液用干燥法制成海藻酸钾细粉，置于自然状态下降至室温后，再用纯净水为湿润剂，用制粒干燥机制成40目～250目的颗粒状粉末，即得低聚海藻酸钾。其中，干燥制粒工艺技术条件：干燥：进风温度＝160℃～180℃，出风温度＝80℃～90℃；制粒：温度控制在50℃～60℃的条件下操作。
低聚海藻酸纳的制备以海藻酸钠为原料，在乙醇中用盐酸酸化后将海藻酸钠转化成海藻酸，分离出酸性乙醇后再用水做溶剂，用氢氧化钠做pH值调节剂，其它所用工艺，设备与制备低聚海藻酸钾一样。
经检测，上述制备的低聚海藻酸钾乌氏黏度为3-16；其中均分子量为700道尔顿-10,000道尔顿；甘露糖醛酸单元与古罗糖醛酸单元的摩尔比值为0.3-3.3。
低聚海藻酸钾样品制备成颗粒剂或散剂。按人体体重60Kg计算，日服1次，每次2.8克，辅助降血压效果完全可以达到国家保健食品要求的标准。降压功效半衰期较长(可达144小时)，低聚海藻酸钾添加到各类食品中(如：奶制品，调味品等)其中低聚海藻酸钾摄入2.8克以上均可达到国家保健食品要求的辅助降血压标准。
低聚海藻酸钾摄食试验
试验人群选择自发高血压患者，试验人群每组30人，摄食含35％氯化钾低钠盐的为对照组，每日摄食含35％氯化钾低钠盐9.0克，其中氯化钠5.9克，氯化钾3.1克。摄食低聚海藻酸钾为试验组，每日摄食低聚海藻酸钾2.8克。摄食一个月，每一天均对每位摄食者的收缩压及舒张压进行测试记录.观察结果列入下表1-4。
表1.一般情况比较        
Figure PCTCN2015073094-appb-000001
Figure PCTCN2015073094-appb-000002
Figure PCTCN2015073094-appb-000003
表2.收缩压变化比较         (mmHg，
Figure PCTCN2015073094-appb-000004
)
项目 试食前 试食中 差值 试食后 差值
实施例1 148.97±13.41 142.83±9.52** 6.13±9.35 133.22±11.52*** 15.75±14.90
表3.舒张压变化比较              (mmHg，
Figure PCTCN2015073094-appb-000005
)
项目 试食前 试食中 差值 试食后 差值
实施例1 97.40±9.64 91.27±8.11*** 6.13±8.00 86.55±11.05*** 10.82±10.59
表4.降压功效比较
分组 倒数 显效 有效 无效 总有效率(％)
实施例1 30 10 15 5 83.33
实施例2、褐藻胰酶水解法制备海藻低聚肽
以褐藻类海带科的海藻裙带菜为例，组成如下：水分15-18，蛋白质10-16，脂肪1-2，糖类38-45(约含海藻酸20)，纤维2-3。灰分18-30。海藻作为一种天然传统食品含天门冬氨酸3.40，亮氨酸2.72，赖氨酸1.34，丙氨酸2.7，脯氨酸1.48等。除上述各种营养成分外，还含有大量碘和其它各种可溶性金属微量元素类营养成分。
1.海藻的准备
海藻原料经粉碎后倒入带夹层的不锈钢反应锅中，加入5％醋酸溶液浸没海藻，浸泡24h以溶解其中的酸可溶性物质，随后将醋酸从包裹有多层纱布的底部排水管中排出，然后注入去离子水反复浸泡。彻底冲洗残留的醋酸至溶液的pH为中性，添加去离子水使海藻和水的重量比约为1∶20，随后在双层反应锅的夹层中通入热蒸汽，升高锅内水温至80℃，然后打开反应锅内的自动搅拌器，边搅拌边缓慢加入10％ NaOH溶液，调溶液pH为8.0，连续搅拌直至反应锅内的海藻呈糊状。
加热和加碱的目的是：1)杀灭溶液中的细菌，防止在酶解过程中细菌繁殖而降低海藻蛋白质的营养学价值；2)由于海藻不溶于水，但可以溶于热碱溶液中，故加入NaOH溶液可以起到助溶作用；3)热和碱作用可使海藻发生变性，蛋白质的空间结构发生改变，肽链间化学键发生断裂，更易于被蛋白酶分解；4)调整溶液的pH，使胰酶可以发挥最大生物活性。
2.酶解反应
维持反应锅内溶液80℃的温度至少半小时，然后由夹层通入自来水降低锅内溶液温度至50℃，按海藻干重的3％加入需要量的胰酶(四川德博尔制药有限公司10,000U/g)，在搅拌器连续搅拌下开始酶解反应，期间调整通入反应锅夹层的蒸汽量使温度维持在50℃。酶解反应过程中，特别是酶解反应前期，由于胰酶的水解作用，海藻的蛋白不断地被分解生成多肽，多肽继续被分解成为短链的肽，甚至在胺肽酶或氨肽酶作用下生成少量游离氨基酸。由于多肽、小肽或氨基酸为两性电解质，等电点多数偏酸性，所以在反应过程中，随生成的肽逐渐增多整个反应体系的pH值会不断降低，为保证胰酶的最大生物活性使反应液的pH维持在8.0，这就需要不断在反应液中加入NaOH稀溶液。自加入胰酶起6h后酶解反应结束。此时，加大蒸汽的通入量使酶解液升温至80℃维持30min，其作用有二：一是将胰酶灭活以终止酶解反应；二是再次杀灭反应液中杂菌防止在随后的处理过程中细菌增殖。
3.过滤处理
酶解反应液分别经板框压滤机和微滤压缩机过滤。板框压滤机的滤膜是由两层厚棉纱布强化固定的加厚滤纸，微滤压缩机中采用过滤孔径为0.5μm石英滤芯，二者过滤除去反应液中较大粒度的胰酶制剂颗粒。使用板框压滤机前，先用蒸馏水从过滤液进口通道压入清水，保证除滤清液出口外没有水从其他处 漏出，以证明板框压滤机状况良好。使用微滤压缩机前，先将石英滤芯放于5％NaOH稀溶液中进行清洗，然后用蒸馏水冲净，以保证最好的过滤效果。
在过滤后的酶解液中加入10％盐酸进行中和，调节酶解液至中性。为了促进海藻蛋白溶解，或酶解过程中为维持酶解反应液pH值的稳定，加入了相当量的NaOH，随后被盐酸中和转化成大量的氯化钠，氯化钠占海藻蛋白重量比超过了10％。
4.浓缩、干燥处理
经真空浓缩泵进行真空低温浓缩，使溶液中大量的水分在真空低压下蒸发，随后经干燥塔喷雾干燥，最后得到胰酶水解海藻蛋白生产的小肽制品即得到海藻低聚肽。
实施例3、木瓜蛋白酶对海藻蛋白的酶解
木瓜蛋白酶对海藻(海带)蛋白的酶解，温度由40℃升至50℃，氨基氮溶出增加明显。温度进一步升高时，增加不明显并随温度增加有下降的趋势。这是因为适当加热，使蛋白质结构疏松，暴露出更多的酶作用位点，同时酶活性也达到了最佳作用状态，随着温度继续升高酶活性逐渐降低，导致氨基氮含量亦降低。因此，我们选择50℃为水解的最佳作用温度。酶的最大反应温度为60℃，在此温度条件下，温浴100min的仍然保持70％的酶活。酶解pH对酶解反应的影响水解条件：酶用量2.5％，固液比1∶3，时间6h，水解温度50℃。据有关资料得知，木瓜蛋白酶的最适pH值在6.7左右，因此，选取了6.25、6.5、6.75、7、7.255个水平。木瓜蛋白酶对海藻的酶解结果表明酶的最适反应pH值为7.5，在pH 9.0的碱性条件下有较好的适应性。2.0％-2.5％的海藻分离 溶液经木瓜蛋白酶水解后，丝氨酸、苏氨酸、脯氨酸、组氨酸、蛋氨酸等游离氨基酸含量明显增加，多肽每100mL提高92mg-98mg。
木瓜蛋白酶水解的最佳水解工艺。单因素试验表明在酶解时间约5h、底物浓度为4％、加酶量约5,500U/g-10,000U/g、pH值为7.0～7.5范围内，温度为50℃时，木瓜蛋白酶水解效果较好。正交试验表明，3因素的影响顺序为：加酶量＞底物浓度＞水解时间；最佳水解工艺为：水解液pH值7.5，加酶量为5,500U/g-10,000U/g，底物浓度为4％，温度50℃，水解6h，在此条件下水解度可达到37.89％采用木瓜蛋白酶进行水解可获得较高水解度的酶解液。
实施例4、本申请低聚海藻酸钾的毒性药理药效学试验
1、急性毒性试验：小鼠、大鼠最大耐受量试验，实施例1制备的低聚海藻酸钾对两种性别小鼠、大鼠在观察期间进食，饮水活动正常，无中毒现象，皮毛光亮，无死亡。样品对两种性别小鼠、大鼠经口最大耐受剂量均大于4.50g/kg.BW；
2、三项遗传毒性试验：1)Ames试验：各剂量组回变菌落数均未超过样品溶剂对照组回变菌落数1倍以上，亦无剂量一反应关系，对鼠伤寒沙门氏菌TA97、TA98、TA100、TA102四株试验菌株(卫生部国家疾病控制中心)，在加与不加肝微粒体酶活化系统时，结果均为阴性，而且试验结果可重复。2)小鼠骨髓细胞微核试验：各剂量组两种性别小鼠骨髓嗜多染红细胞与成熟红细胞的比值(PCE/NCE)在1.25～1.36之间，未见样品对两种性别小鼠的骨髓细胞有明显抑制作用。各剂量组两种性别小鼠骨髓嗜多染红细胞微核率与样品溶剂对照组比较，无显著性差异(P＞0.05)，而环磷酰胺组两种性别小鼠骨髓 嗜多染红细胞微核率与样品溶剂对照组比较，有显著性差异(P＜0.01)，未见样品对两种性别小鼠骨髓细胞染色体有明显损伤作用。
3、小鼠精子畸形试验：各剂量组小鼠精子畸形率与样品溶剂对照组比较，无显著性差异(P＞0.05)，而环磷酰胺组小鼠精子畸形率与样品溶剂对照组比较，有显著性差异(P＜0.01)，未见样品对雄性小鼠生殖细胞有明显损伤作用。
综合以上试验结果，得出试验结论：急性毒性试验结果表明实施例1制备的低聚海藻酸钾对两种性别小鼠、大鼠经口最大耐受剂量均大于4.50g/kg.BW。三项遗传毒性试验均为阴性，表明低聚海藻酸钾无遗传毒性作用。
低聚海藻酸钾是以高分子的海藻酸钾为原料经降解得到的，降解过程实质上也是精制去多酚、蛋白质和复杂的碳水化合物等杂质过程，口服经过精制的低聚海藻酸钾不会产生过敏反应。
实施例5、本申请低聚海藻酸钾的药理药效学实验
一、低聚海藻酸钾对大鼠粪便排钠量的影响
方法采用尾脉搏间接测压法测定SHRs收缩压，40只大鼠随机分为5组：空白溶媒对照组、氢氯噻嗪片剂组(6.25mg/kg)、低聚海藻酸钾高剂量、中剂量和低剂量组(500mg/kg、250mg/kg、100mg/kg)，每天灌胃给低聚海藻酸钾，连续给低聚海藻酸钾28d；每周测量血压，并观察停药后3d、6d的血压变化。收集SHRs大鼠粪便以供测定粪便中的含钠量。结果与同期溶媒对照组比较，连续给药21d和28d，氢氯噻嗪和低分子海藻酸钾3个剂量组的SHRs血压水平均降低(P＜0.01)；停药3d和6d时，6.25mg/kg氢氯噻嗪的降压作用消失(P＜0.05)；在停药3d时，低聚海藻酸钾高、中、低3个剂量组的 收缩压均低于同期溶媒对照组(P＜0.05或P＜0.01)；停药6d时，250mg/kg及500mg/kg低分子海藻酸钾仍可降低SHRs血压水平(P＜0.01)。结论低聚海藻酸钾连续口服给药可剂量依赖性地降低SHRs血压，且停药6d仍呈现持续的降压作用，中、高剂量组粪便中钠的排泄量比对照2组存在显著性差异
表1.对大鼠粪便排钠量的影响(1-5天)(
Figure PCTCN2015073094-appb-000006
n＝10)
Figure PCTCN2015073094-appb-000007
与模型对比*p＜0.05   **p＜0.01  与氢氯噻嗪比  ☆p＜0.05☆☆p＜0.01
表2.对大鼠粪便排钠量的影响(6-10天)(
Figure PCTCN2015073094-appb-000008
   n＝10)
Figure PCTCN2015073094-appb-000009
Figure PCTCN2015073094-appb-000010
与模型对比  *p＜0.05  **p＜0.01  与氢氯噻嗪比  ☆p＜0.05☆☆p＜0.01
二、低聚海藻酸钾对饮用高盐溶液大鼠的影响
1.材料
1.1实验动物
雄性SD大鼠，体重180g-220g，由成都中医药大学动物中心提供。饲养条件20℃±2℃，12h/12h昼夜节律。动物饲养在大鼠代谢笼内，自由饮水进食。
1.2试剂
实施例1制备的低聚海藻酸钾(low molecular weight potassium alginate，PA)，淡黄色粉末，每日溶于大鼠饮用水中自由饮用。
氯化钠(sodium chloride)，白色结晶性粉末，批号20080928，天津市致远化学试剂有限公司，每日溶于蒸馏水中配制所需浓度供大鼠自由饮用。
68％硝酸(nitric acid)，分析纯，无色透明液体，批号20071108，成都市欣海兴化工试剂厂，临用前溶于蒸馏水中配制成10％的硝酸溶液。用于容器的无钠处理。
硝酸(nitric acid)，优级纯，无色透明液体，批号090211，四川西陇化工有限公司，直接用于样品消化。
高氯酸(perchloric acid)，优级纯，无色透明液体，批号20080708，天津市东方化工厂，直接用于样品消化。
1.3仪器
SOLAA原子吸收分光光度计：型号M6，Thermo Elemental
台式离心机：4000～40000转/分，型号TGL-16G，上海安亭科技仪器厂。
电热恒温水槽：型号DK-600，上海精宏实验设备有限公司。
Eppendorf可调式移液器：100μL-1000μL，德国eppendorf公司。
Finnpipette可调式移液器：20μL-200μL，芬兰finnpipette公司。
电子天平：型号BS210S，北京赛多利斯天平有限公司。
电子天平：型号BS3000，上海友声衡器有限公司。
2.方法
2.1试剂的配制
2.0％ NaCl饮用水的配制：称取25g NaCl溶于适量蒸馏水中，最后定容至1250ml备用；
0.5％ NaCl饮用水的配制：取2.0％ NaCl饮用水125mL，加入蒸馏水定容至500mL，即得；
2.0％ NaCl/0.1％ PA饮用水的配制：称取低分子海藻酸钾粉末0.625g，溶于适量2.0％ NaCl饮用水中，最后定容至625mL备用；
0.5％ NaCl/0.025％ PA饮用水的配制：取2.0％ NaCl-PA饮用水125mL，加入蒸馏水定容至500mL，即得。
10％硝酸溶液的配制：取68％浓硝酸溶液1000mL，加入5800mL蒸馏水，即得。
2.2无钠处理
将收集血清、尿样和粪样的代谢笼具、EP管、锥形瓶浸泡于10％硝酸溶液中过夜，然后用去离子水淋洗烘干备用。
2.3低聚海藻酸钾对大鼠水盐代谢的影响
40只SD雄性大鼠随机分成5组：空白溶媒对照组，0.5％ NaCl组，2.0％ NaCl组，0.5％ NaCl/0.025％ PA组，2.0％ NaCl/0.1％ PA组，每组8只。各组的饮用水按照表3的方法配制。
表3.各组大鼠饮用水配方
Figure PCTCN2015073094-appb-000011
大鼠自由饮水进食，每天测量大鼠24h饮水量、摄食量、尿量。分别在饲养第0天、30天、60天，尾静脉取血并常规分离血清，留取大鼠24h尿样、 粪样。血清与尿样于-20℃保存备用。粪样的处理：将粪便在60的干燥12小时后，碾碎，置干燥器中保存备用。
2.4电解质测定方法
实验结束后，同步盲法取100μL血清，用超纯水定容至5mL；取50μL大鼠尿液，用超纯水定容5mL；称取0.1g粪便于50mL经过无钠处理的锥形瓶中，加入5mL浓硝酸和0.5mL高氯酸消化成白色晶体后，加超纯水定容至10mL。采用原子吸收光度法检测血清、尿及粪中钠、钾离子含量，计算各组大鼠血清钠和血清钾含量，以及24小时尿和粪便中排泄的钠、钾离子量。
实验结果用均数±标准差(X±s)表示，采用SPSS11.5软件包对其进行方差分析，组间两两比较采用One-Way ANOVA检验。结果见表4～8。
3.结果
3.1低聚海藻酸钾对大鼠一般生理指标的影响
由表4可见，在60天实验过程，与同期空白溶媒对照组比较，0.5％ NaCl模型组和0.5％ NaCl/0.025％低聚海藻酸钾实验组大鼠的体重未见明显差异(P＞0.05)，但2.0％ NaCl模型组大鼠体重在30天后明显降低(P＜0.01)；与2.0％ NaCl模型组比较，2.0％ NaCl/0.1％低聚海藻酸钾实验组大鼠体重在60天时明显降低(P＜0.05)。
由表5可见，在60天给药过程，与同期空白溶媒对照组比较，各组动物摄食量未见明显差异。
由表5可见，与同期空白溶媒对照组比较，0.5％ NaCl模型组尿量有增加趋势；2.0％ NaCl模型组尿量在30天时有明显增加，而在60天时呈现一定耐受现象，尿量仅有轻度增加。与同期0.5％ NaCl模型组比较，0.5％ NaCl/0.025％低聚海藻酸钾实验组大鼠尿量没有明显变化；与同期2.0％ NaCl模型组比较， 2.0％ NaCl/0.1％低聚海藻酸钾实验组大鼠尿量在30天时稍有增加，而在60天时非常明显增加(P＜0.01)。
由表5可见，与同期空白溶媒对照组比较，0.5％ NaCl模型组和0.5％ NaCl/0.025％低聚海藻酸钾实验组大鼠饮水量都没有明显变化，而2.0％ NaCl模型组和2.0％ NaCl/0.1％低聚海藻酸钾实验组大鼠饮水量有显著增加(P＜0.01)，其中2.0％ NaCl/0.1％低聚海藻酸钾实验组饮水量在30天时明显高于2.0％ NaCl模型组增加(P＜0.05)。
3.2低聚海藻酸钾对大鼠尿液电解质排泄的影响
表6显示，在给药60天时，与0.5％ NaCl模型组比较，混合饮用0.5％ NaCl/0.025％低聚海藻酸钾实验组大鼠尿钠排泄量有轻度增加，在给药30及60天时，尿钾的排泄量也有增加趋势，但差异均没有统计学意义(P＞0.05)。
此外，在30天和60时，2.0％ NaCl模型组大鼠尿钠的排泄量与溶媒对照组比较有明显的增加(P＜0.05或P＜0.01)，尿钾的排泄量60天时有增加趋势，但差异没有统计学意义(P＞0.05)。与2.0％ NaCl模型组比较，在30天时混合饮用2.0％ NaCl/0.1％低聚海藻酸钾实验组大鼠尿钠排泄量有增加趋势，而在60天时有非常明显增加(P＜0.01)；尿钾的排泄在30天和60天都有明显的增加(P＜0.05或P＜0.01)。
3.3低聚海藻酸钾对大鼠粪便电解质排泄的影响
由表7可见，在60天实验过程，与同期空白溶媒组比较，单纯饮用0.5％或2.0％ NaCl饮用水，以及混合饮用0.5％ NaCl/0.025％低聚海藻酸钾或2.0％ NaCl/0.1％低分子海藻酸钾饮用水对SD大鼠粪钠和粪钾的排泄量没有影响。
3.4低聚海藻酸钾对大鼠血清电解质的影响
由表8可见，在60天实验过程，与同期空白溶媒组比较，单纯饮用0.5％或2.0％ NaCl饮用水，以及混合饮用0.5％ NaCl/0.025％低聚海藻酸钾或2.0％NaCl/0.1％低聚海藻酸钾饮用水的大鼠血清钠浓度没有显著性差异(P＞0.01)；在给药60天时，与单纯饮用2.0％ NaCl饮用水的模型对照组比较，混合饮用2.0％ NaCl/0.1％低聚海藻酸钾的大鼠血清钾有显著性增加(P＜0.01)，但其它各实验组的血清钾没有明显变化。
4、小结
本实验结果显示：低聚海藻酸钾对大鼠一般生理指标及电解质有剂量相关性的调节作用。
在大鼠自由饮用按照2％盐溶液添加5％比例的低聚海藻酸钾(0.1％)溶液60天后，低聚海藻酸钾对动物摄食量和饮水量未见明显影响，但可非常明显增加尿量而同时明显减轻大鼠体重，低聚海藻酸钾减轻体重的作用可能与尿量增加所致的全身体液量降低有关。此外，上述用量的低聚海藻酸钾可显著增加尿钠和尿钾排泄量，同时可显著增加血钾水平，而对粪钠和粪钾排泄及血清钠浓度未见明显影响。
表4.低聚海藻酸钾(PA)对大鼠体重的影响(x±s，n＝8)
Figure PCTCN2015073094-appb-000012
Figure PCTCN2015073094-appb-000013
**P＜0.01，与同期空白溶媒对照组比较；#P＜0.05，与同期2.0％NaCl模型对照组比较
Figure PCTCN2015073094-appb-000014
Figure PCTCN2015073094-appb-000015
低聚海藻酸钾为乳白色或黄色颗粒状粉末，有吸湿性，其水溶液粘度低，适宜开发成保健用低钠盐，低聚海藻酸钾以褐藻类提取物药用海藻酸为原料，经降解成盐，而制得的低聚合度的海藻酸的钾盐。
我国传统中医药认为海带具有消痰散结，利水消肿的功效。低聚海藻酸钾是从褐藻门植物海带中提取并经降解工艺制备而得。研究结果显示：连续灌胃给药21天及28天后，100mg/kg、250mg/kg或500mg/kg低聚海藻酸钾均可非常显著地降低自发性高血压大鼠SHRs血压水平，其作用强度与6.5mg/kg氢氯噻嗪(相当于临床等效量的3倍～12倍)相似。停药3天后，氢氯噻嗪的降压作用消失；但在停药3天时，低聚海藻酸钾高、中、低三个剂量均具有显著降压作用；停药6天时，250mg/kg及500mg/kg低聚海藻酸钾仍具有非常显著的降压作用。我们进一步的放射药动学研究结果显示：低聚海藻酸钾口服给药后在小鼠体内的半衰期为36.28小时，提示低聚海藻酸钾停药后持续的降压作用可能与其体内消除缓慢有关。
人体的钾主要来自食物，大部分由小肠迅速吸收。钾占人体无机盐的5％，是人体必需的营养素。临床研究表明，原发性高血压病人尿中钾排出量比正常人低，而适量的补钾对轻症高血压及有高血压因素的某些正常血压者有降压作用，这可能与钾对水和体液平衡的调节作用有关。动物实验结果也表明：适量的补钾可降低高血压动物的血压水平。
综上所述，来源于天然藻类植物的低聚海藻酸钾，分子量小、利于吸收，对SHRs有非常显著而持续的降压作用，其降压作用的机理可能与低聚海藻酸本身或低分子海藻酸与钾离子相互作用(例如低聚海藻酸影响钾离子体内的药动学特性)有关。体外实验提示：低聚海藻酸钾PA对离体血管平滑肌有剂量相关的、非内皮依赖性的舒张作用，其机制可能与抑制血管平滑肌细胞电压依赖性钙通道有关。
低聚海藻酸钾样品按人体体重60Kg计算，日服1次，每次2.8克，辅助降压效果完全可以达到国家保健食品要求的标准。降压功效半衰期较长(可达144小时)。
实施例6、含低聚海藻酸钾低钠盐的制备
本实施例中，低聚海藻酸钾按照实施例1的方法制备；海藻低聚肽按照实施例2的方法制备
本实施例中的低钠盐由下述组分组成：NaCl  550g、低聚海藻酸钾160g、海藻低聚肽  60g、琥珀酸  2.9g。
在研钵中粉碎市售(纯净质量)NaCl、和琥珀酸，并在90微米筛上筛分。从穿过筛子的级分中取550克NaCl(d50为59微米)，2.9克琥珀酸(d50为58微米)，与160克低聚海藻酸钾(d50为58微米)，低聚海藻酸钾喷洒按干重计60克海藻低聚肽溶液，充分混合。由这种混合物在Herzog压片机上使用1.0t/cm2压力(相当于100MPa的压力)制造50克丸片(40毫米直径，20毫米高度)。将所得丸片沿直径破碎，并在Frewitt筛磨机上使用6毫米、3毫米和最后1毫米的筛研磨。使用710微米、500微米、280微米和90微米的筛将来自该Frewitt筛磨机的产品筛分成级分。进一步分析级分280微米至710微米(即合并两个级分)并确定具有396微米的d50的低钠盐。
实施例7、含低聚海藻酸钾低钠盐的制备
本实施例中，低聚海藻酸钾按照实施例1的方法制备；海藻低聚肽按照实施例2的方法制备。
该实施例的低钠盐含有71.5％(重量)的NaCl，22％(重量)的低聚海藻酸钾、6％(重量)的海藻低聚肽和0.5％(重量)酵母水解物(核糖核苷酸)。
在以500rpm运行的Alpine 160UPZ针磨机上研磨NaCl。将磨碎的NaCl(d50＝69μm)与未磨的海藻酸钾及海藻低聚肽(d50＝58μm)一起以1.5千克批量装入2升Nautamixer中，并于19rpm混合至少10分钟。将混合粉末收集在料仓中，从中以50克份额手动供给Herzog压片机。施加的压力为0.5t/cm2至1.0t/cm2(相当于50至100MPa的压力)。大多数丸片在1.0t/cm2压力下压制。大多数丸片的尺寸为40毫米直径和～20毫米高度。将所得丸片沿直径破碎。
在预先破碎后，采用直径200毫米、辊距3.0毫米、辊速195rpm和300rpm的Merz光辊粉碎机进行丸片的进一步粉碎。在Merz光辊粉碎机上再一 次粉碎产品(现在以0.8毫米辊距运行)。将粉碎的产品在配有200微米和710微米筛的Mogensen Piccolo上筛分。进一步分析级分200微米至710微米并确定具有455微米的d50的低钠盐。
实施例8、含低聚海藻酸钾低钠盐的制备
本实施例中，低聚海藻酸钾按照实施例1的方法制备；贝类低聚肽的制备方法如下所述：
木瓜蛋白酶对贝类蛋白的酶解，取干贝鲜品10千克，均质成糊，温度由40℃升至50℃，氨基氮溶出增加明显。温度进一步升高时，增加不明显并随温度增加有下降的趋势。这是因为适当加热，使蛋白质结构疏松，暴露出更多的酶作用位点，同时酶活性也达到了最佳作用状态，随着温度继续升高酶活性逐渐降低，导致氨基氮含量亦降低。因此，我们选择50℃为水解的最佳作用温度。酶的最大反应温度为60℃，在此温度条件下，温浴100min的仍然保持70％的酶活。酶解pH对酶解反应的影响水解条件：酶用量2.5％，固液比1∶3，时间6h，水解温度50℃。据有关资料得知，木瓜蛋白酶的最适pH值在6.7左右，因此，选取了6.25、6.5、6.75、7、7.255个水平。木瓜蛋白酶对干贝的酶解结果表明酶的最适反应pH值为7.6，在pH 9.0的碱性条件下有较好的适应性。2.0％-2.5％的干贝均质分离溶液经木瓜蛋白酶水解后，丝氨酸、苏氨酸、脯氨酸、组氨酸、蛋氨酸等游离氨基酸含量明显增加，干贝多肽每100mL提高92mg-98mg。
木瓜蛋白酶水解的最佳水解工艺。单因素试验表明在酶解时间约5h、底物浓度为4％、加酶量约5,500U/g-10,000G/g、pH值为7.0～7.5范围内，温度为50℃时，木瓜蛋白酶水解效果较好。正交试验表明，3因素的影响顺序为：加酶量＞底物浓度＞水解时间；最佳水解工艺为：水解液pH值7.5，加酶量为5,500U/g-10,000G/g，底物浓度为4％，温度50℃，水解6h，在此条件下水解度可达到37.25％采用木瓜蛋白酶进行水解可获得较高水解度的酶解液。
本实施例中的低钠盐由下述组分组成：NaCl  500g、低聚海藻酸钾126g、贝类低聚肽  45g、琥珀酸  2.9g。
具体的制备方法如下所述：
取纯净质量NaCl(500克，d50为375微米)、低聚海藻酸钾(126克，d50为296微米)、琥珀酸(2.9克，d50为464微米)和贝类低聚肽(45克，d50为58微米)并充分混合。由该混合物在Herzog压片机上制造50克丸片(40毫米直径，20毫米高度)。施加的压力为1.0t/cm2压力(相当于100MPa的压力)。将所得丸片沿直径破碎，并在Frewitt筛磨机上使用6毫米、3毫米和最后1毫米的筛研磨。使用710微米、500微米、280微米和90微米的筛将来自该Frewitt筛磨机的产品筛分成级分。检查低于90微米、90微米至280微米(d50为231微米)、280微米至500微米(d50为381微米)、500微米至710微米(d50为587微米)和高于710微米的级分。进一步分析级分90微米至710微米并确定具有445微米的d50的低钠盐。
实施例9、含低聚海藻酸钾低钠盐的制备
本实施例中，低聚海藻酸钾按照实施例1的方法制备；玉米低聚肽的制备方法如下所述：
木瓜蛋白酶对玉米蛋白的酶解，取玉米蛋白粉2千克，加3升水浸泡过夜，糊化后将玉米蛋白糊温度由40℃升至50℃，氨基氮溶出增加明显。温度进一步升高时，增加不明显并随温度增加有下降的趋势。这是因为适当加热，使蛋白质结构疏松，暴露出更多的酶作用位点，同时酶活性也达到了最佳作用状态，随着温度继续升高酶活性逐渐降低，导致氨基氮含量亦降低。因此，我们选择50℃为水解的最佳作用温度。酶的最大反应温度为60℃，在此温度条件下，温浴100min的仍然保持70％的酶活。酶解pH对酶解反应的影响水解条件：酶用量2.5％，固液比1∶3，时间6h，水解温度50℃。据有关资料得知，木瓜蛋白酶的最适pH值在6.7左右，因此，选取了6.25、6.5、6.75、7、7.255个水平。木瓜蛋白酶对玉米蛋白的酶解结果表明酶的最适反应pH值为7.8，在pH 9.0的碱性条件下有较好的适应性。25％均质糊状物经木瓜蛋白酶水解后，丝氨酸、苏氨酸、脯氨酸、组氨酸、蛋氨酸等游离氨基酸含量明显增加，玉米多肽每100mL提高94mg-98mg。
木瓜蛋白酶水解的最佳水解工艺。单因素试验表明在酶解时间约5h、底物浓度为4％、加酶量约5,500U/g、pH值为7.0～7.5范围内，温度为50℃时，木瓜蛋白酶水解效果较好。正交试验表明，3因素的影响顺序为：加酶量＞底物浓度＞水解时间；最佳水解工艺为：水解液pH值7.8，加酶量为5,500U/g，底物浓度为4％，温度50℃，水解6h，在此条件下水解度可达到37.45％采用木瓜蛋白酶进行水解可获得较高水解度的酶解液。
该实施例的低钠盐含有72％(重量)NaCl含有20％(重量)低聚海藻酸钾和7.5％(重量)玉米低聚肽，还含有0.3％(重量)酵母提取物(核糖核苷酸)和0.2％(重量)海藻酸镁。
使用市售NaCl(d50＝375μm)和自制的低聚海藻酸钾(d50＝296μm)制造该低钠盐。将这些组分与d50为86微米的未磨的玉米低聚肽及酵母提取物(核糖核苷酸)海藻酸镁一起装料并混合。由该混合物在Herzog压片机上使用1.0t/cm2压力(相当于100MPa的压力)制造50克丸片(40毫米直径，20毫米高度)。将所得丸片沿直径破碎，并在Frewitt筛磨机上使用6毫米、3毫米和最后1毫米的筛研磨。分析级分得到90微米-200微米和200微米-710微米的粒子的组分分布，90微米至710微米并确定具有435微米的d50。
实施例10、含低聚海藻酸钾低钠盐的制备
本实施例中，低聚海藻酸钾按照实施例1的方法制备；海藻低聚肽按照实施例2的方法制备
本实施例中的低钠盐由下述质量百分的组分组成：NaCl  74.7％、低聚海藻酸钾  18.4％、海藻低聚肽  6.7％、海藻酸镁  0.2％。
将160克低聚海藻酸钾(d50为258微米)，喷洒海藻低聚肽溶液120mL(按干重计58.26克)后混合，加入650克NaCl(d50为39微米)和1.74g海藻酸镁，在造粒机上造粒，过280微米筛，得到含低聚海藻酸钾及海藻低聚肽的低钠盐干燥后为785克，进一步分析级分280微米至710微米(即合并两个级分)并确定具有598微米的d50。余留下NaCl供下一次制备含低聚海藻酸钾及海藻低聚肽的低钠盐样品用。
实施例11、含低聚海藻酸钾低钠盐的制备
本实施例中，低聚海藻酸钾按照实施例1的方法制备；贝类低聚肽按照实施例8的方法制备。
将160克低聚海藻酸钾(d50为258微米)喷洒贝类低聚肽溶液120mL(按干重计58.26克)混合，加入650克NaCl(d50为39微米)和1.74g海藻酸镁，在造粒机上造粒，由这种混合物在Herzog压片机上使用1.0t/cm2压力(相当于100MPa的压力)制造50克丸片(40毫米直径，20毫米高度)。将所得丸片沿直径破碎，并在Frewitt筛磨机上使用6毫米、3毫米和最后1毫米的筛研磨。使用710微米、500微米、280微米和90微米的筛将来自该Frewitt筛磨机的产品筛分成级分。进一步分析级分280微米至710微米(即合并两个级分)并确定具有498微米的d50的低钠盐。
实施例12、含低聚海藻酸钾低钠盐的制备
本实施例中，低聚海藻酸钾按照实施例1的方法制备；玉米低聚肽按照实施例9的方法制备
该实施例的低钠盐含有72％(重量)NaCl、20.5％(重量)低聚海藻酸钾和7％(重量)玉米低聚肽，0.5％(重量)酵母提取物(核糖核苷酸)。
使用市售NaCl(d50＝375μm)和自制的低聚海藻酸钾(d50＝296μm)制造该配制物。将这些组分与d50为86微米的未磨的玉米低聚肽及酵母提取物一起装料并混合。由该混合物在Herzog压片机上使用1.0t/cm2压力(相当于100MPa的压力)制造50克丸片(40毫米直径，20毫米高度)。将所得丸片沿直径破碎，并在Frewitt筛磨机上使用6毫米、3毫米和最后1毫米的筛研磨。分析级分得到90微米-200微米和200微米-710微米的粒子的组分分布，90微米至710微米并确定具有438微米的d50的低钠盐。
实施例13、含低聚海藻酸钾低钠盐的制备
本实施例中，低聚海藻酸钾按照实施例1的方法制备；海藻低聚肽按照实施例2的方法制备
将100克低聚海藻酸钾(d50为258微米)喷洒海藻低聚肽溶液120mL(按干重计48.75克)混合，加入500克NaCl(d50为39微米)和2.25g海藻酸镁，在造粒机上造粒，由这种混合物在Herzog压片机上使用1.0t/cm2压力(相当于100MPa的压力)制造50克丸片(40毫米直径，20毫米高度)。将所得丸片沿直径破碎，并在Frewitt筛磨机上使用6毫米、3毫米和最后1毫米的筛研磨。使用710微米、500微米、280微米和90微米的筛将来自该Frewitt筛磨机的产品筛分成级分。进一步分析级分280微米至710微米(即合并两个级分)并确定具有498微米的d50的低钠盐。
实施例14、含低聚海藻酸钾低钠盐的制备
本实施例中，低聚海藻酸钾按照实施例1的方法制备；海藻低聚肽按照实施例2的方法制备
将171.76克低聚海藻酸钾(d50为258微米)喷洒海藻低聚肽溶液120mL(按干重计54.59克)混合，加入501.46克NaCl(d50为39微米)(其中含有1.46g海藻酸镁)，在造粒机上造粒，由这种混合物在Herzog压片机上使用1.0t/cm2压力(相当于100MPa的压力)制造50克丸片(40毫米直径，20毫米高度)。将所得丸片沿直径破碎，并在Frewitt筛磨机上使用6毫米、3毫米和最后1毫米的筛研磨。使用710微米、500微米、280微米和90微米的筛将来自该Frewitt筛磨机的产品筛分成级分。进一步分析级分280微米至710微米(即合并两个级分)并确定具有498微米的d50的低钠盐。
实施例15、含海藻酸钾低钠盐的沸腾干燥加工方法
本实施例中，低钠盐含有72％(重量)NaCl、20.5％(重量)低聚海藻酸钾和7％(重量)海藻低聚肽，0.4％(重量)酵母提取物(核糖核苷酸)及0.1％钙锌镁矿物质。
a.底喷海藻酸钾用于氯化钠细粒的功能性海藻酸盐包衣。
底喷装置是由一个圆锥形的物料槽及内置的圆柱形隔圈组成，物料槽底部装有不同直径分布孔的导流板，以分隔圈内外的气流状态。隔圈内气流最大，物料在隔圈内高速向上运动，进入扩展室后落入隔圈外，隔圈外物料自 动流入隔圈内，如此循环。加液雾化喷嘴安装导流板中心，喷嘴自下向上喷液，方向与氯化钠细粒物料、气流方向一致。
b.顶喷用于海藻酸钾干燥、氯化钠细粒的功能性海藻酸盐包衣制粒。
顶喷装置是由一个锥形的物料槽及扩展室组成。由于物料槽是锥形的，保证了物料槽内的喷泉式流化状态，入风气流推动料槽内的物料向上进入扩展室，由于扩展室直径大于物料槽，入风流速下降，物料因自身重力大于风力时下降，氯化钠细粒物料在料槽及扩展室内往返运动。在扩展室顶部有多个喷嘴安装口，可用于在制粒及包衣过程中喷入雾化液体。
沸腾干燥工艺研究
海藻酸钾海藻肽组合物浓度以干重计为20％，按海藻酸钾海藻肽组合物中含有酵母水解液及钙锌镁矿物质的物料温度为40℃～60℃、60℃～80℃、80℃～100℃，喷液速度20～25升/小时、25～35升/小时、35～40升/小时进行筛选，结果：海藻酸钾海藻肽组合物物料温度为40℃～60℃时，物料温度过低，粉粒不易干燥，易结块。喷液速度为20～25升/小时，喷液速度低，流量小，影响效率。喷液速度为35～40升/小时，喷液速度快，粉粒不易干燥完全，易结块。物料温度为80℃～100℃时，物料温度过高，可能会引起组合物中间体中有效成分的分解。故选择海藻酸盐物料温度为60℃～80℃、浓度20％，喷液速度25～35升/小时为直径小于600微米的氯化钠细粒物料12-25千克通过沸腾干燥条件对氯化钠细粒物料进行功能性海藻酸钾(钠)包衣制粒。沸腾干燥条件分别采用了底喷海藻酸钾海藻肽组合物液，顶喷用于海藻酸钾海藻肽组合物液均可得到品质良好的含低聚海藻酸钾海藻肽的d50为630微米的颗粒，继续加入调味剂及矿物质的糊状物，搅拌干燥得低钠盐样品。
实施例16、本申请的含海藻酸钾低钠盐的降血压效果试验
一、将实施例6-15制备的含低聚海藻酸钾低钠盐分别进行降血压效果试验，具体方法如下所述：
采用尾脉搏间接测压法测定SHRs收缩压，40只大鼠随机分为4组，每组10只：空白溶媒对照组、海藻酸钾低钠盐以海藻酸钾计高剂量、中剂量和 低剂量组(500mg/kg、250mg/kg、100mg/kg)，每天灌胃给药，连续给药28d；每周测量血压，并观察停药后3d、6d的血压变化。连续给药21d和低分子海藻酸钾3个剂量组的SHRs血压水平均降低(P＜0.01)；停药3d和6d时，在停药3d时，海藻酸钾低钠盐高、中、低3个剂量组的收缩压均低于同期溶媒对照组(P＜0.05或P＜0.01)；停药6d时，250mg/kg及500mg/kg海藻酸钾低钠盐仍可降低SHRs血压水平(P＜0.01)。结论海藻酸钾低钠盐连续口服给药可剂量依赖性地降低SHRs血压，且停药6d仍呈现持续的降压作用，这可能与海藻酸钾低钠盐口服给药后体内消除缓慢有关。降血压效果试验结果如表9所示。
表9.海藻酸钾低钠盐(以海藻酸钾计)对SHR大鼠血压的影响(mmHg)
Figure PCTCN2015073094-appb-000016
Figure PCTCN2015073094-appb-000017
二、海藻酸钾低钠盐摄食试验
试验人群选择自发高血压患者，试验人群每组30人，摄食含35％氯化钾低钠盐的为对照组，每日摄食含35％氯化钾低钠盐9.0克，其中氯化钠5.9 克，氯化钾3.1克。摄食含低聚海藻酸钾低钠盐的为试验组，每日摄食含低聚海藻酸钾低钠盐9.0克(分别实施例6-15的方法制备的含低聚海藻酸钾低钠盐)。摄食一个月，每一天均对每位摄食者的收缩压及舒张压进行测试记录。观察结果列入下表10-13。
表10.一般情况比较          
Figure PCTCN2015073094-appb-000018
Figure PCTCN2015073094-appb-000019
表11.收缩压变化比较              (mmHg，
Figure PCTCN2015073094-appb-000020
)
项目 试食前 试食中 差值 试食后 差值
实施例6 148.97±13.41 142.83±9.50** 6.13±9.35 133.20±11.52*** 15.77±14.90
实施例7 148.97±13.48 142.84±9.51** 6.03±9.32 133.30±11.55*** 15.67±14.91
实施例8 148.94±13.71 142.82±9.52** 6.12±9.34 133.20±11.58*** 15.84±14.92
实施例9 148.92±13.62 142.83±9.52** 6.09±9.31 133.30±11.62*** 15.62±14.90
实施例10 148.94±13.26 142.85±9.53** 6.09±9.30 133.30±11.57*** 15.64±14.90
实施例11 148.98±13.81 142.82±9.54** 6.16±9.33 133.10±11.61*** 15.88±14.95
实施例12 148.93±13.39 142.84±9.54** 6.09±9.36 133.20±11.44*** 15.73±14.90
实施例13 148.98±13.53 142.84±9.52** 6.14±9.33 133.20±11.65*** 15.78±14.90
实施例14 148.90±13.21 142.82±9.55** 6.08±9.33 133.30±11.38*** 15.60±14.90
实施例15 148.89±13.48 142.81±9.50** 6.08±9.35 133.10±11.46*** 15.79±14.90
对照组 151.77±12.55 151.47±12.79## 0.30±12.74 150.33±13.58## 1.43±13.88
表12.舒张压变化比较             (mmHg，
Figure PCTCN2015073094-appb-000021
)
项目 试食前 试食中 差值 试食后 差值
实施例6 97.40±9.64 91.27±8.12*** 6.13±8.00 86.57±11.05*** 10.83±10.59
实施例7 97.30±9.61 91.23±8.22*** 6.07±8.02 86.56±11.04*** 10.74±10.57
实施例8 97.50±9.74 91.17±8.18*** 6.33±7.92 86.58±11.03*** 10.92±10.60
实施例9 97.40±9.48 91.25±8.14*** 6.15±7.98 86.54±11.02*** 10.86±10.58
实施例10 97.50±9.53 91.49±8.18*** 6.11±8.01 86.59±11.06*** 10.91±10.57
实施例11 97.50±9.73 91.29±8.02*** 6.21±8.04 86.56±11.07*** 10.94±10.55
实施例12 97.50±9.94 91.46±8.22*** 6.14±8.02 86.54±11.03*** 10.96±10.61
实施例13 97.50±9.63 91.37±8.15*** 6.13±8.04 86.59±11.07*** 10.91±10.60
实施例14 97.50±9.53 91.47±8.17*** 6.23±8.05 86.55±11.04*** 10.95±10.56
实施例15 97.50±9.56 91.16±8.12*** 6.14±8.01 86.58±11.06*** 10.92±10.59
对照组 99.90±9.76 95.83±10.18** 4.07±6.95 94.73±9.48** 5.17±7.91##
表13.降压功效比较
分组 倒数 显效 有效 无效 总有效率(％)
实施例6 30 10 15 5 83.33
实施例7 30 11 14 5 83.33
实施例8 30 12 13 5 83.33
实施例9 30 15 10 5 83.33
实施例10 30 13 12 5 83.33
实施例11 30 12 13 5 83.33
实施例12 30 11 14 5 83.33
实施例13 30 9 16 5 83.33
实施例14 30 13 12 5 83.33
实施例15 30 12 13 5 83.33
对照组 30 3 4 23 22.33**
上述结果表明，摄食含35％氯化钾低钠盐的高血压患者中，属于容量性高血压的表现出一定的效果，摄食本申请的含低聚海藻酸钾低钠盐的高血压患者的总有效率远远高于摄食含35％氯化钾低钠盐的高血压患者(对照组)。并且，实验证明，摄食含低聚海藻酸钾低钠盐辅助降压效果略高于摄食低聚海藻酸钠低钠盐的，提示钾离子显示出有效的辅助降压效果。
以上所述仅是本公开的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本公开原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视本公开的保护范围。

Claims (23)

  1. 一种低聚海藻酸钾，其重均分子量为700道尔顿-10,000道尔顿，且所述海藻酸中甘露糖醛酸单元与古罗糖醛酸单元的摩尔比值为0.3-3.3，乌氏黏度为3-16。
  2. 根据权利要求1所述的低聚海藻酸钾，其重均分子量为1,000-4,500道尔顿；且所述海藻酸中甘露糖醛酸单元与古罗糖醛酸单元的摩尔比值为0.4-3.3。
  3. 权利要求1或2所述的低聚海藻酸钾在制备辅助降压的保健食品或低钠盐产品中的应用。
  4. 一种含海藻酸钾的低钠盐，包括权利要求1或2所述的低聚海藻酸钾和氯化钠。
  5. 根据权利要求4所述的低钠盐，其中所述氯化钠与低聚海藻酸钾的重量比为(48-83)∶(13-40)。
  6. 根据权利要求4或5所述的低钠盐，其中所述低钠盐中还包括低聚肽。
  7. 根据权利要求6所述的低钠盐，其中所述低聚肽为海藻低聚肽、玉米低聚肽或贝类低聚肽。
  8. 根据权利要求6所述的低钠盐，其中所述氯化钠、低聚海藻酸钾和低聚肽的质量比为(48-83)∶(13-40)∶(3.8-11.5)。
  9. 根据权利要求4-8中任意一项所述的低钠盐，其中所述低钠盐中还包括添加剂，其中所述添加剂为至少一种选自由以下所组成的组：味道改进剂、味道掩蔽剂、矿物质、抗结块剂和流动添加剂，所述氯化钠、所述低聚海藻酸钾、所述低聚肽和所述添加剂的重量比为(48-83)∶(13-40)∶(3.8-11.5)∶(0.2-0.5)。
  10. 根据权利要求9所述的低钠盐，其中所述添加剂占含海藻酸盐低钠盐总重量的0.2％-0.5％。
  11. 根据权利要求9所述的低钠盐，其中所述味道掩蔽剂选自下述物质：食用有机酸；氨基酸及其衍生物；酵母；酵母提取物；来自酵母提取物之类来源的水解蛋白；肽；水解植物蛋白；水解脂肪；核糖核苷酸；类黄酮；氨基酸与二羧酸的酰胺；海藻糖和葡萄糖酸盐中的一种或者两种以上任意组合； 或它们的组合；
    所述味道改进剂选自下述物质中的一种或两种以上任意组合：衍生自多香果、罗勒、辣椒、桂皮、丁香、小茴香、莳萝、大蒜、马郁兰、肉豆蔻、红辣椒、黑胡椒、迷迭香和姜黄中的任一种的香料油性树脂和油；精油；柑橘油；蒜味香料；植物提取物；蛋白质水解产物；天然和人造的混合香料，和通过还原糖与蛋白质衍生组分之间的美拉德型反应制成的加工香料；所述矿物质(微量元素)钙、镁、锌、铬、铁、钼、铜、锰均以海藻酸盐的形式加入。
  12. 根据权利要求9所述的低钠盐，其中所述低钠盐是具有250微米至1毫米的粒径的颗粒。
  13. 根据权利要求12所述的低钠盐，其中所述低钠盐的制备方法包括使用大于150微米的低聚海藻酸钾黏附50微米粒度以下的食盐粉末造粒或再使用40至100MPa的压力压制后粉碎获具有250微米至1毫米的粒径的低钠盐颗粒。
  14. 一种低钠盐的制备方法，包括下述步骤：按照权利要求5所述的组分质量比，使用粒度大于150微米的低聚海藻酸钾黏附粒度为50微米以下的氯化钠粉末造粒或使用粒度大于150微米的低聚海藻酸钾黏附粒度为50微米以下的氯化钠粉末造粒再使用40至100MPa的压力压制后粉碎获具有250微米至1毫米的粒度的低钠盐颗粒。
  15. 一种低钠盐的制备方法，包括下述步骤：按照权利要求8所述组分比例，在d50为258-270微米的低聚海藻酸盐粉中喷洒低聚肽溶液，混合后加入d50为39-50微米的NaCl粉，在造粒机上造粒，干燥，使用280微米的筛，过筛得到含低聚海藻酸钾及低聚肽的低钠盐，并确定具有498-640微米的d50；余留下NaCl供下一次制备含低聚海藻酸钾及低聚肽的低钠盐样品用。
  16. 一种低钠盐的制备方法，包括下述步骤：按照权利要求8所述组分比例，在d50为258-270微米低聚海藻酸钾粉中喷洒低聚肽溶液后混合，加入d50为39-50微米的NaCl粉，在造粒机上造粒，将得到的混合物在Herzog压片机上使用40至100MPa的压力制造丸片；然后将所得丸片沿直径破碎，并在筛磨机研磨筛分得到具有398-520微米的d50的低钠盐颗粒。
  17. 一种低钠盐的制备方法，包括下述步骤：按照权利要求9所述的重量 份数比，将低聚海藻酸盐和低聚肽和除氯化钠以外的其余组分混合制备成干重计为20％的低聚海藻酸盐和低聚肽的组合物溶液，按照低聚海藻酸盐和低聚肽的组合物溶液温度为60℃～80℃、喷液速度25～35升/小时，为直径小于600微米的氯化钠细粒物料12-25千克通过沸腾干燥对氯化钠细粒物料进行包衣得到含低聚海藻酸盐和低聚肽的d50为630微米低钠盐样品；所述沸腾干燥条件采用底喷低聚海藻酸盐和低聚肽的组合物溶液或者顶喷用于低聚海藻酸盐和低聚肽的组合物溶液。
  18. 权利要求1或2所述的低聚海藻酸钾在制备预防或辅助治疗高血压的产品中的应用。
  19. 根据权利要求18所述的应用，其中所述低聚海藻酸钾每日摄入量为2.8克/60kg。
  20. 权利要求在4-13中任意一项所述的低钠盐在制备预防或辅助治疗高血压的产品中的应用。
  21. 一种预防或辅助治疗高血压的方法，包含对受试者施用权利要求1或2所述的低聚海藻酸钾。
  22. 根据权利要求21所述的方法，其中所述低聚海藻酸钾每日摄入量为2.8克/60kg。
  23. 一种预防或辅助治疗高血压的方法，包含对受试者施用权利要求在4-13中任意一项所述的低钠盐。
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