WO2001040315A9 - The alginate having low molecular weight, methods of manufacturing it and its use - Google Patents
The alginate having low molecular weight, methods of manufacturing it and its useInfo
- Publication number
- WO2001040315A9 WO2001040315A9 PCT/CN1999/000202 CN9900202W WO0140315A9 WO 2001040315 A9 WO2001040315 A9 WO 2001040315A9 CN 9900202 W CN9900202 W CN 9900202W WO 0140315 A9 WO0140315 A9 WO 0140315A9
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- molecular weight
- alginate
- daltons
- alginic acid
- molecules
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/734—Alginic acid
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
Definitions
- the present invention relates to a low molecular weight alginate. More specifically, the present invention relates to an alginate with alginic acid as a raw material and an average molecular weight obtained by a degradation method of about 5000-20,000 Daltons. The viscosity characteristic viscosity number is between 1 and 20, and the molecular weight of most of the alginate molecules is between 1,000 and 30,000 Daltons. The invention also relates to a method for preparing such a low molecular weight alginate and its use in the prevention and treatment of high blood pressure and primary aldosteronism (ALD) and blood glucose reduction.
- ALD primary aldosteronism
- Natural alginic acid is a very common substance that can be extracted from marine plants such as kelp, kelp, brown algae, and macroalgae, and has a wide range of uses. Natural alginic acid and its derivatives are used to lower blood pressure and prevent hypertension. Drugs for this disease have long been documented in the literature.
- Kelp is a relatively abundant resource in the ocean and is widely cultivated on the coastlines in many places. In the coastal areas of China, kelp roots are used to reduce the symptoms of hypertension. Ingestion of 12 grams per day has a certain effect on primary or secondary primary hypertension. People extract alginic acid or its salts from plants such as kelp and use it in various applications. For example, adults taking more than 20 grams of sodium alginate daily have a temporary hypotensive effect. Some people have also used potassium alginate in SHR spontaneously hypertensive rat experiments, and found that animal experiments are effective, but for humans, hypertension patients with large molecular weight potassium alginate have no significant effect.
- Japanese Patent Application Laid-Open No. 6-237783 discloses an alginic acid prepared by using alginic acid as a raw material for preventing hypertension and having health effects. Oligosaccharides and their preparation methods, they use degrading enzymes that can degrade polysaccharides to prepare potassium alginate belonging to oligosaccharides with a degree of polymerization of 2-5 from natural alginic acid, but the purpose of the product is only to prevent (inhibit) hypertension There is no treatment effect on hypertension.
- CN1097307 discloses a seaweed slimming agent, which is obtained by the following methods: submerging and immersing a commercially-available medicinal alginic acid in water to make it swell, and then adding 6-7N hydrochloric acid to degrade the alginic acid into an oligomer. After deacidification, a saturated ethanolic solution of potassium hydroxide was added to convert it into potassium oligoalginate. Finally, the pH was stabilized at 8, dried, and pulverized to obtain a powdery brown alga slimming agent.
- the molecular weight of the product and the effect of lowering blood pressure are not specifically described in the patent, nor is the effect of treating hypertension and hyperaldosteronism emphasized.
- WO9320826 A1 discloses an alginate-based pharmaceutical composition for preventing and treating gastrointestinal disorders.
- US5460957 discloses a new alginate oligosaccharide compound containing calcium and potassium ions, but not sodium, It is used as a hypotensive additive in foods.
- the alginate oligosaccharide (I) is obtained by (1) treating sodium alginate or potassium alginate ( ⁇ ) with a glycanase (II), and then (2) replacing sodium (or sodium and sodium) with calcium or potassium ions. Potassium) ions, and / or calcium and other potassium ions.
- the product of this patent has a degree of polymerization of 2 to 5 and a low molecular weight.
- KR9200242 discloses a method for preparing low-molecular-weight alginate, which only uses ultrasonic treatment to decompose the polymer main chain, but the molecular weight of the product is generally above 35,000, and repeated ultrasonic treatment can only reach 20,000 or above 20,000. The role of preventing and treating hypertension is not indicated in the patent.
- KR9105768 discloses a method for extracting sodium alginate from brown algae.
- the molecular weight of the product is between 60,000-300,000.
- US5283076 discloses a food or beverage containing sodium alginate having a molecular weight of 10,000 to 150,000, which is used to prevent obesity and diabetes.
- JP3273002 discloses a decomposition substance of alginic acid, which has a molecular weight of 1000-1500 and is used as a stabilizer for food or medicine.
- US4104460 discloses a method for extracting alginic acid from seaweed, which includes adding a hydrogen peroxide compound to alginic acid and then treating it with a base such as sodium carbonate, ammonium carbonate, sodium hydroxide, etc., but it is not mentioned in the literature as a drug the use of.
- the alginate derivatives obtained in the prior art can only work within a short period of time, mainly suppressing the increase in blood pressure, but generally have no therapeutic effect.
- the object of the present invention is to provide an alginic acid (salt) derivative, which is required to prevent and treat hypertension and aldosteronism with a prominent effect and a long duration of action, and at the same time a blood glucose lowering effect.
- alginic acid salt
- oxidation oxidation, enzymatic methods, etc.
- alginic acid and its salts are effective in treating hypertension.
- aldosteronism are very effective and can lower blood sugar.
- the research work of the present invention is divided into three stages.
- the average molecular weight of the alginate initially prepared is 6.8 X 10 4.
- the molecular weight of most of the alginate molecules is between 2000 and 100,000, and the molecular weight above 50,000 is separated. After being dropped, the remainder was clinically observed by Xiyuan Hospital of China Academy of Traditional Chinese Medicine. Taking 5-8 grams daily has a significant effect on patients with essential hypertension, with a total effective rate of 83.3%.
- the second phase we are preparing a low molecular weight alginate, molecular weight average molecular weight of 3.5 X 10 4 and most of the alginate molecule is between 2,000 to 58,000, daily doses of 4-7 g
- the total effective rate of patients with essential hypertension reached 85%.
- a lower molecular weight alginate with an average molecular weight between 5000-20,000, preferably between 7000-12,000 and particularly more preferably between 6000-10,000 and most preferably between 7000-9000 between.
- the molecular weight of most of the alginate molecules is between 1,000-30,000 and preferably between 1,600-20,000, especially between 1600-12,000, and especially between 1,600- 10,000 and most preferably between 1800 and 10,000.
- the albednate product has an inherent viscosity number between 1-20 and preferably between 3-14. Especially, when the alginate has an average molecular weight between 6000-9000 and the molecular weight of most of the alginate molecules is in the range of 1600-10,000, the daily dosage is 0.5 to 3 grams of the alginate.
- the total effective rate of patients with essential hypertension reached more than 88%, and after taking it continuously for a week, the patient's blood pressure stabilized at a normal level within 2 to 3 days. Therefore, the present invention was completed in the third stage.
- the invention provides a low-molecular-weight alginate. More specifically, the invention provides alginic acid as a raw material, and an average molecular weight obtained by a combination of a degradation method and a membrane separation technology is about 5000-20,000, and preferably 7000. -Alginates between 12,000 and particularly preferably between 7500 and 8500. Preferably, the molecular weight of most of the alginate molecules is between 1,000 and 30,000 and more preferably between 1,600 and 20,000 and most preferably between 1,600 and 10,000.
- the Uighur viscosity intrinsic viscosity number of the alginate product is between 1 and 20, and the salt-forming cation of the alginate is a pharmaceutically acceptable cation or trivalent chromium ion.
- the present invention also provides a method for preparing such a low-molecular-weight alginate and its use in preventing and treating hypertension and primary aldosteronism and reducing blood sugar.
- the degradation step includes a physical method, a photochemical method, an immobilized enzyme method, or a chemical method.
- Physical methods include ultrasonic treatment or high-speed shear processing: photochemical methods use light radiation and catalysis for processing; and chemical methods use strong acids, strong bases, and inorganic or organic oxidants.
- oxidants are required, and these oxidants include organic and inorganic oxidants. It includes hydrogen peroxide, peracetic acid, potassium peroxide, potassium peroxide, potassium (sodium) perborate, potassium permanganate, persulfate hinge, potassium persulfate double salt, sodium chlorite, potassium chlorite, and many more.
- the present invention uses DHFM series ZBS type 1 and ZBS type 3 hollow fiber ultrafiltration membranes produced by the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences to cut molecular weights of 10,000 and 30,000, respectively, and cut off alginates with molecular weights greater than 10,000 or 30,000, respectively. Then, using the NF4040 nano-filter membrane, which is produced by Dalian Institute of Chemical Physics Membrane Engineering Center, is a brand name that can filter out alginates with a molecular weight of less than 1000 or 1200 (slightly pressurized).
- the “most part” in the phrase “the molecular weight of most of the alginic acid (salt) molecules” is explained: Since the pore sizes of the ultrafiltration membrane and the nanofiltration membrane are not absolutely uniform, there are a few slightly larger or Slightly smaller filter pores, and the pore size will change under different pressures, so the molecular weight cut-off can be modified with “mostly”. For example, when using a nanofiltration membrane to filter, the original design trapped 1,000 molecules, but because the filter pores are not strictly uniform and the filter pores change with pressure, a small number of molecules with a molecular weight slightly higher than 1000 (such as the molecular weight of 1200) will also Missed.
- the invention provides a method for preparing a low-molecular-weight alginate, which comprises: (1) a degradation step: degrading a high-molecular-weight alginic acid raw material to an average molecular weight of more than 20,000 to about 80,000 Daltons, adding an alkali solution to dissolve it (2) Use ultrafiltration method to cut off molecules with a molecular weight above 30,000 Daltons, leaving the molecules behind Alginate molecules with an amount of less than 30,000 Daltons, and (3) using a nanofiltration membrane to cut off alginate molecules with a molecular weight of less than 1,000 Daltons, resulting in an average molecular weight between 5000 and 20000 Daltons and a large The molecular weight of some of the alginate molecules is in the range of 1,000 to 30,000 Daltons, and finally dried.
- a method for preparing a low-molecular-weight alginate which comprises: (1) a degradation step: degrading a high-molecular-weight alginic acid raw material to a molecular weight of more than 20,000 to 80,000 Daltons; (2) preparing the degradation product by treating it with an alkali Soluble salts, (3) add water or a water-containing medium under stirring, and then add an oxidant to further degrade the product into a lower molecular weight alginate, (4) use ultrafiltration to cut off molecules with a molecular weight above 30,000 Daltons Leaving alginate molecules with a molecular weight of less than 30,000 Daltons, and (5) using a nanofiltration membrane to cut off alginate molecules with a molecular weight of less than 1000 Daltons to obtain an average molecular weight between 5000 and 20000 Daltons and The molecular weight of most of the alginate molecules is in the range of 1000 to 30,000 Daltons, and finally dried.
- a method for preparing low-molecular-weight alginic acid comprising: (1) a degradation step: degrading a high-molecular-weight alginic acid raw material to an average molecular weight of more than 10,000 to about 70,000 Daltons by adding an alkali solution to dissolve it; (2) utilizing The ultrafiltration method cuts off molecules with a molecular weight of more than 10,000 Daltons, leaving alginic acid molecules with a molecular weight of less than 10,000 Daltons, and (3) uses a nanofiltration membrane to cut off alginic acid molecules with a molecular weight of less than 1200 Daltons, The average molecular weight is between 5000-8000 Daltons and the molecular weight of most of the alginate molecules is in the range of 1200-1,0000 Daltons, and finally dried.
- a method for preparing a low-molecular-weight alginate which comprises: (1) a degradation step: degrading a high-molecular-weight alginic acid raw material to a molecular weight of more than 10,000 to 70,000 Daltons; (2) preparing the degradation product by treating it with an alkali Soluble salts, (3) add water or an aqueous medium under stirring, and then add an oxidant to further degrade the product to a lower molecular weight alginate, (4) use ultrafiltration to cut off molecules with a molecular weight above 10,000 Daltons Leaving alginate molecules with a molecular weight of less than 10,000 Daltons, and (5) using a nanofiltration membrane to cut off alginate molecules with a molecular weight of less than 1200 Daltons to obtain an average molecular weight between 5000 and 7000 Daltons and The molecular weight of most of the alginate molecules is in the range of 1200-10,000 Daltons, and finally dried.
- the degradation steps in these preparation methods include methods such as physical degradation, photochemical degradation and chemical degradation, and immobilized enzymes.
- Physical methods include ultrasonic treatment and high-speed shearing; photochemical methods use light radiation and catalytic treatment; and chemical methods use strong acids, strong bases, and inorganic or organic oxidants for processing.
- the small molecule alginate that can be absorbed into the blood vessels through the intestinal mucosa is the main functional component of alginate that plays a role in lowering blood pressure, and it is also the main component effective for primary aldosteronism. And the amount absorbed by the intestinal tract is reduced. As the molecular weight increases, the alginate absorbed by the intestinal mucosa becomes less and less. Only the alginate containing potassium has a certain effect. Alginate regulates blood pressure only because of the combination of alginic acid and sodium ions in the intestinal tract, and regulates blood pressure through sodium-potassium ion exchange. In other words, in order to play a greater role, alginate must be absorbed by the intestine, so the molecular weight is the key.
- the molecular weight of alginate is too small (for example, less than 900), and although it is easy to absorb, it can show a hypotensive effect, but the maintenance time is short.
- Alginate containing chromium has the effect of lowering blood sugar.
- the content of chromium in alginate generally accounts for 0.01% to 0.05% of the total weight of alginate.
- Daily consumption of 6-8g of chromium containing alginate has a significant reduction. Sugar effect.
- the alginic acid used in the present invention is extracted from marine plants, especially from kelp, kombu, and brown algae, where kelp is a rich and cheap resource.
- kelp is a rich and cheap resource.
- the method for preparing such high molecular weight alginic acid or its salt from marine plants as long as the molecular weight and molecular weight distribution are within the ranges specified above.
- the salt of the present invention may be any pharmaceutically acceptable salt, that is, a pharmaceutically acceptable salt.
- Salt-forming cations include, for example, cations of alkali metals, alkaline earth metals, iron, zinc, chromium (III), manganese, and ammonium ions. Of these, soluble alginates are preferred, and potassium salts are most preferred.
- alginic acid and alginic acid have the same meaning, as do "alginate” and "alginate”.
- the "molecular weight” used here is determined by column chromatography:
- the instruments used are HL-2 constant flow pumps produced by Shanghai Huxi Instrument Factory and BSZ-100 automatic partial collectors, as well as produced by Shanghai Analytical Instrument Factory 222 spectrophotometer; because alginic acid or its salt is a polysaccharide, Dextran with different molecular weights is used as a control, the average molecular weight of Dextran T4-6 is 5,000, and the average molecular weight of Dextran T8-12 is 10200, Dextran T60-90 has an average molecular weight of 68300, Dextran T100 has an average molecular weight of 100,000, and Dextran 200-300 has an average molecular weight of 266,000.
- This series of Dextran are products of the Swedish Pharmacia company and are manufactured by Farco Chemical Supplies of Hong Kong. Provided: Sephacryls-300 as the column chromatography; Determination conditions: 50ml in total, 0.1 molar sodium chloride solution as eluent, flow rate lml / min, collection: lml / tube; detection method: take about 10mg of sample, add lml water to dissolve it, add resorcinol hydrochloride solution, heat to boil, it will show reddish purple, this product is mannuronic acid and guluronic acid Heteropolymer bound potassium salt can be generated with a phloroglucinol compound of a purple solution of hydrochloric acid; then detected by means of a spectrophotometer, Shimadzu spectrophotometer or an alginate in the absorbance at 230nm.
- the insoluble alginate is converted to a soluble salt (such as sodium or potassium) by ion exchange before measuring its molecular weight.
- a soluble salt such as sodium or potassium
- calcium alginate is first converted to alginic acid precipitate by adding hydrochloric acid, and then using hydrogen Treatment with aqueous sodium oxide solution converts to water-soluble sodium alginate.
- the Uighur viscosity intrinsic viscosity number is determined according to the Chinese Pharmacopoeia 1995 edition, Appendix VI G: Viscosity test method, with a 0.2% by weight seaweed salt concentration.
- Figure 1 is an infrared absorption spectrum of a low-molecular-weight potassium alginate of Example 1;
- Figure 2 is an infrared absorption spectrum of a high molecular weight alginic acid raw material;
- Fig. 4 is a 'H-NMR spectrum of a high molecular weight alginic acid raw material.
- alginic acid a nationally approved medicinal alginic acid produced by the Dalian Algae Industry Company of China
- alginic acid a nationally approved medicinal alginic acid produced by the Dalian Algae Industry Company of China
- a DHFM series ZBS 3 type hollow fiber ultrafiltration membrane (using 0.15Mpa pressure) produced by the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences was used to cut the molecular weight of 30,000 and cut off the potassium alginate with a molecular weight of more than 30,000 to obtain potassium alginate with a molecular weight of less than 30,000.
- the solution Then, the F4040 nanofiltration membrane (pressurized by 0.15 MPa) produced by Dalian Institute of Chemical Physics and its membrane engineering center was used for dehydration and filtration of alginate with a molecular weight of less than 1200. After two filtrations, the molecular weight was obtained. Products with a distribution range of 1,200-30,000. A double molecular weight of 95% ethanol was added to the product to precipitate a low molecular weight potassium alginate. The precipitate was dried and its average molecular weight was 16,000 as determined by column chromatography.
- the cut off potassium alginate having a molecular weight of more than 30,000 is used as a part of the raw material, and a certain amount of original commercially available alginate raw material is replenished, and the above operation is repeated.
- the low-molecular-weight algal potassium of this example was subjected to infrared analysis and 'H-NMR spectrum test, and compared with the raw alginic acid.
- the infrared spectra of FIG. 1 and FIG. 2 were compared, and the 1 H-NMR spectra of FIG. 3 and FIG. 4 were compared.
- the results show that the molecular structure has not changed substantially before and after degradation.
- the first stage Weigh 500g of alginic acid (Nationally approved medicinal grade alginic acid produced by Dalian Algae Industry Company, China). Add alginic acid to distilled water, stir well, make the alginic acid account for 9% of the total water, heat to 40 ° C (reaction temperature), and drop in hydrogen peroxide (containing H 2 0 2 30%) while stirring to make the system
- the final hydrogen peroxide concentration (referred to as the final H 2 0 2 concentration) is 1% of the total weight.
- the second stage Use DHFM series ZBS type 1 hollow fiber ultrafiltration membrane (using 0.15Mpa pressure) to cut 10,000 molecular weight and cut off potassium alginate with molecular weight greater than 10,000 to obtain a solution of potassium alginate with molecular weight less than 10,000. Then, using a Bert brand NF4040 nanometer filter membrane (using a pressure of 0.1 Mpa) for dehydration and filtration of alginates with a molecular weight of less than 1,000, after two filtrations, a product with a molecular weight distribution ranging from 1,000 to 10,000 was obtained. It was then dried and its average molecular weight was 7,500 as measured by column chromatography. The cut off potassium alginate with a molecular weight greater than 10,000 is used as a part of the raw material, and a certain amount of the original commercially-available alginic acid raw material is replenished, and the above operations are repeated.
- Example 2 The procedure of Example 2 was repeated, except that the reaction temperature and the final hydrogen peroxide concentration are shown in Table 1 below. Table 1: Experimental results
- a DHFM series ZBS type 1 hollow fiber ultrafiltration membrane was used to cut the molecular weight of 10,000 and cut off the potassium alginate with a molecular weight of more than 10,000 to obtain a solution of potassium alginate with a molecular weight of less than 10,000. Then, use a Bert brand NF4040 nanofiltration membrane to dehydrate and filter out alginates with a molecular weight of less than 1000. After two filtrations, a product with a molecular weight distribution range of 1,000-10,000 was obtained. A double volume of 95% ethanol was added to the product to precipitate a low-molecular-weight potassium alginate, and the precipitate was dried. The average molecular weight was 7000 measured by column chromatography, and the intrinsic viscosity was 3.
- the DHFM series ZBS 1 hollow fiber ultrafiltration membrane was used to cut the molecular weight to 10,000. , Then, use Bert NF4040 type nanofiltration membrane removes alginate with a molecular weight of less than 1000 and dehydrates and concentrates it into a 5% paddle. Adds twice the volume of 95% ethanol equivalent to its own volume to settle and dry to obtain seaweed with an average molecular weight of 8,000. Potassium acid.
- the cut off potassium alginate with a molecular weight greater than 10,000 is used as a part of the raw material, and a certain amount of the original commercially-available alginic acid raw material is replenished, and the above operation is repeated.
- the average molecular weight of the product obtained by using a reaction temperature of 80 ° C and a concentration of 6% by column chromatography was 6,000.
- Example 12 The procedure used was similar to that in Example 12, except that a 20% aqueous solution of potassium peroxide was replaced with a 30% aqueous solution of potassium carbonate.
- Example 15 Degradation method of immobilized enzyme
- Immobilized enzyme degradation technology can improve the utilization rate of the enzyme. Based on the research results of EMERY, AN (Chem Eng., 71, 1972), it is improved. Porous sodium glass spheres are used, with a capillary pore size of 600-800 angstroms and a ball diameter of 1 mm. Soak the porous sodium glass spheres at 45 ° C for 24 hours with a 5% 1 ⁇ 14 solution, and then wash away the unabsorbed titanium tetrachloride with distilled water.
- the nanofiltration membrane is operated, precipitated with 95% ethanol equivalent to twice the volume of the product, and dried to obtain potassium alginate having an average molecular weight of 7000.
- the titanium oxide pellets can be recycled and reused.
- the alginic acid raw material is subjected to oxidative degradation treatment with hydrogen peroxide.
- the amount of hydrogen peroxide added should be such that hydrogen peroxide accounts for 1% to 3% of the weight of the mixed slurry of alginic acid and water, and the heating temperature is 40%.
- the reaction was carried out at 80 ° C, and the oxidation time was 2 hours.
- 30% sodium hydroxide solution was added to the oxidized alginic acid to convert it into low-molecular-weight sodium alginate.
- the ultrafiltration and nanometers of the previous examples were repeated using ZBS1 and NF4040 nanofiltration membranes. The filtration membrane was operated to obtain sodium alginate having an average molecular weight of 8000.
- a 5% calcium chloride aqueous solution was added to obtain an insoluble calcium alginate precipitate, which was washed with distilled water, and the generated hydrochloric acid was removed to make the pH near neutral and dried.
- Example 19 Preparation method of low molecular weight alginic acid
- Example 2 100 g of the low molecular weight alginate of Example 2 was treated with 10% HC1 to obtain a low molecular weight alginic acid precipitate, washed with distilled water, and then dried.
- the pharmaceutical preparation is prepared as follows:
- Example 19 The low-molecular-weight alginic acid of Example 19 was used to fill capsules. Each capsule was 0.5 g, and about 4 capsules were taken daily.
- plastic pouch with alginate with an average molecular weight of 8000, 1 lg per bag, and take 1 to 2 bags daily. If plastic sachets are filled with alginate with an average molecular weight of 18,000, 2 g per bag, take 1 to 2 bags daily.
- the common medicinal starch sold on the market was mixed with alginate with an average molecular weight of 8000 at a ratio of 1: 3, and the tablets were compressed on a tableting machine so that each tablet weighed 0.7 g, and 4 tablets were taken daily.
- Capsules, granules and tablets are recommended after meals.
- Low molecular weight potassium alginate can treat hyperaldosteronism associated with hypertension.
- RIA radioimmunoassay
- the plasma aldosterone levels of 10 subjects were calculated.
- the average ALD level before treatment 235ng / L
- the average ALD level after treatment 172ng / L
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AU15027/00A AU1502700A (en) | 1999-11-30 | 1999-11-30 | The alginate having low molecular weight, methods of manufacturing it and its use |
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CN1310954C (en) * | 2003-04-15 | 2007-04-18 | 哈尔滨工程大学 | Preparation method of chromium alginate |
CN101104649B (en) * | 2006-07-12 | 2011-05-18 | 谭攸恒 | Potassium alginate and composition thereof |
WO2009086685A1 (en) * | 2007-12-29 | 2009-07-16 | Dalian Yaweite Bioengineering Co., Ltd. | An alginic acid with low molecular weight, its salts, uses, preparative methods, pharmaceutical compositions and foods |
JP2010187659A (en) * | 2009-01-20 | 2010-09-02 | Kao Corp | Purified alginic acid or salt thereof |
CN104311696B (en) * | 2014-09-26 | 2017-04-26 | 大连雅威特生物技术股份有限公司 | Application of oligomeric sodium alginate in preparation of medicines, health products and salt products |
CN112037931B (en) * | 2020-07-15 | 2023-10-20 | 新疆维吾尔自治区人民医院 | Aldosteronism prediction system for use in suspected primary aldosteronism |
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JPH02225422A (en) * | 1989-02-28 | 1990-09-07 | Kimitsu Kagaku Kogyo Kk | Medicine composition |
JPH03273002A (en) * | 1990-03-22 | 1991-12-04 | Otsuka Chem Co Ltd | Alginic acid decomposition product |
JP3024994B2 (en) * | 1990-10-31 | 2000-03-27 | マルハ株式会社 | Production method and purification method of alginate oligosaccharide |
JP2643669B2 (en) * | 1990-12-28 | 1997-08-20 | 共成製薬株式会社 | Algin-containing foods |
JP2663408B2 (en) * | 1991-05-09 | 1997-10-15 | 明治製菓株式会社 | Method for promoting plant morphogenesis or differentiation |
JPH0517315A (en) * | 1991-07-03 | 1993-01-26 | Sankin Kogyo Kk | Alginic acid salt impression material composition for dental use |
JPH05304974A (en) * | 1992-03-06 | 1993-11-19 | Maruha Corp | Calcium aliginate oligosaccharide and its production |
GB2266532B (en) * | 1992-04-28 | 1996-09-04 | Taiyo Fishery Co Ltd | Alginate oligosaccharides methods for their production and their use in foodstuffs |
CN1089619A (en) * | 1993-01-06 | 1994-07-20 | 山东烟台西苑制药厂 | A kind of production method of propylene glycol alginate sodium sulfate |
JP2986324B2 (en) * | 1993-11-26 | 1999-12-06 | 明治製菓株式会社 | Diet / Diabetic Food |
JP3825069B2 (en) * | 1994-07-14 | 2006-09-20 | マルハ株式会社 | Human epidermal keratinocyte activator |
CN1081194C (en) * | 1996-12-18 | 2002-03-20 | 谭攸恒 | Process for preparing potassium alginate and its use |
JPH1180204A (en) * | 1997-09-05 | 1999-03-26 | Nikka Chem Co Ltd | Method for hydrolyzing alginic acid and hydrolyzed material |
JP3617912B2 (en) * | 1997-10-08 | 2005-02-09 | 日本原子力研究所 | Plant growth promoter |
-
1999
- 1999-11-30 AU AU15027/00A patent/AU1502700A/en not_active Abandoned
- 1999-11-30 CA CA002430277A patent/CA2430277A1/en not_active Abandoned
- 1999-11-30 WO PCT/CN1999/000202 patent/WO2001040315A1/en active Application Filing
Also Published As
Publication number | Publication date |
---|---|
AU1502700A (en) | 2001-06-12 |
WO2001040315A1 (en) | 2001-06-07 |
WO2001040315A8 (en) | 2002-03-21 |
CA2430277A1 (en) | 2001-07-06 |
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