WO2001040315A1 - Alginate a faible poids moleculaire, son procede de preparation et ses applications - Google Patents

Alginate a faible poids moleculaire, son procede de preparation et ses applications Download PDF

Info

Publication number
WO2001040315A1
WO2001040315A1 PCT/CN1999/000202 CN9900202W WO0140315A1 WO 2001040315 A1 WO2001040315 A1 WO 2001040315A1 CN 9900202 W CN9900202 W CN 9900202W WO 0140315 A1 WO0140315 A1 WO 0140315A1
Authority
WO
WIPO (PCT)
Prior art keywords
molecular weight
alginate
daltons
alginic acid
molecules
Prior art date
Application number
PCT/CN1999/000202
Other languages
English (en)
Chinese (zh)
Other versions
WO2001040315A9 (fr
WO2001040315A8 (fr
Inventor
Chuanxing Yu
Original Assignee
Dalian Yaweite Biology Engineering Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dalian Yaweite Biology Engineering Co., Ltd. filed Critical Dalian Yaweite Biology Engineering Co., Ltd.
Priority to PCT/CN1999/000202 priority Critical patent/WO2001040315A1/fr
Priority to AU15027/00A priority patent/AU1502700A/en
Priority to CA002430277A priority patent/CA2430277A1/fr
Publication of WO2001040315A1 publication Critical patent/WO2001040315A1/fr
Publication of WO2001040315A9 publication Critical patent/WO2001040315A9/fr
Publication of WO2001040315A8 publication Critical patent/WO2001040315A8/fr

Links

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 aldosterone (ALD) and blood glucose reduction.
  • ALD primary aldosterone
  • 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.
  • CNI097307 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 alginic acid into an oligomer. After deacidification, a saturated ethanol solution of potassium hydroxide was added to convert it into potassium alginate oligosaccharide. Finally, the pH was stabilized at 8, dried, and pulverized to obtain a powdered 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 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 ⁇ 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 molecular weight of most of the alginate molecules is between 1,000 and 30,000 and preferably between 1,600 and 20,000, especially between 1600 and 12,000, and especially between 1,600 and 10,000 and most preferably between 1800 and 10,000.
  • the albednate product has an inherent viscosity number between 1 and 20 and preferably between 3 and 14.
  • 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, a daily dosage of 0.5-3 g of the alginate versus the original
  • 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 percarbonate, potassium (sodium) perborate, potassium permanganate, ammonium persulfate, double salts of potassium persulfate, 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 ones. 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 and 8000 Daltons and the molecular weight of most of the alginate molecules is in the range of 1200 to 10,000 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 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 to reduce blood pressure and is also the main component effective for primary aldosteronism.
  • Alginate with a molecular weight greater than 12,000 passes through the intestinal mucosa 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.
  • alginate in order to play a greater role, alginate must be absorbed by the intestine, so the molecular weight is the key. It is worth mentioning that 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 reducing blood sugar. The content of chromium in alginate generally accounts for 0.01% to 0.05% of the total weight of alginate. Taking 6-8g of alginate containing chromium daily 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 (111), manganese, and the like, 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 type constant flow pumps produced by Shanghai Huxi Instrument Factory and BSZ-100 automatic partial collectors, and also 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.
  • Dextran T4-6 has an average molecular weight of 5,000
  • Dextran T8-12 has an average molecular weight of 10200
  • -90 has an average molecular weight of 68300
  • Dextran T100 has an average molecular weight of 100,000
  • Dextran 200-300 has an average molecular weight of 266,000.
  • This series of Dextran are products of the Swedish Pharmacia company and are provided by Farco Chemical Supplies of Hong Kong;
  • the column chromatography packing was Sephacryls-300; the measurement conditions: a total of 50ml, the eluent was a 0.1 molar concentration sodium chloride solution, the flow rate was 1ml / min, and the collection was: 1ml / tube; detection method: take about 10mg of the sample, add 1ml of water Dissolve it, add resorcinol hydrochloride solution, heat and 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 in accordance with the Chinese Pharmacopoeia 1995 edition, Appendix VI G: Viscosity Test Method, with 0.2 ⁇ % 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 NF4040 nanofiltration membrane (pressurized at 0.15 MPa) produced by Dalian Institute of Chemical Physics and its membrane engineering center was used for dehydration and filtration to remove alginates 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-NM spectrum test, and compared with raw material 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, and stir evenly so that the alginic acid accounts for 9% of the total water. Heat to 40 ° C (reaction temperature). Add hydrogen peroxide (containing H 2 0 2 30%) dropwise 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 reaction is carried out for 2 hours under stirring, and the unreacted hydrogen peroxide is removed by decomposition after heating up to 80 ° C, and then under stirring Add 30% potassium hydroxide solution to alginic acid treated with hydrogen peroxide dropwise, and add an appropriate amount of distilled water to fully dissolve the product, and finally keep the pH of the system between 6-7. At this time, the average molecular weight of the product is 65000.
  • the intrinsic viscosity numbers of the products are shown in Table 1.
  • Second stage Use DHFM series ZBS type 1 hollow fiber ultrafiltration membrane (using 0.15Mpa pressure) to cut molecular weight 10,000, cut off potassium alginate with molecular weight greater than 10,000, and obtain a solution of potassium alginate with molecular weight less than 10,000. Then, using a Bert brand NF4040 type nanofiltration membrane (depressed with a pressure of 101 MPa) to dehydrate and filter out 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
  • the 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, a bert brand NF4040 nanofiltration membrane was used for dehydration and alginate with a molecular weight of less than 1000. After two filtrations, a product with a molecular weight distribution ranging from 1,000 to 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 molecular weight was 10,000 using a DHFM series ZBS 1 hollow fiber ultrafiltration membrane. And then use the Burt card NF4040 type nanofiltration membrane filters out alginate with a molecular weight of less than 1000 and dehydrates it to concentrate into a 5% slurry. Adds 95% ethanol equivalent to twice its 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. The porous sodium glass ball was immersed in a 5% 11 4 solution at 45 ° C for 24 hours, and then the titanium tetrachloride not absorbed was washed with distilled water.
  • the porous glass ball soaked with titanium tetrachloride was placed in alginic acid Decomposing enzyme (see Japanese patent Application JP 6-237783) in a 2% concentration solution, soaked at 2 ° C for 18 hours, packed the porous glass spheres soaked with alginate-degrading enzyme into a column chromatography test packing column, and kept at 40-55 ° C.
  • Titanium oxide powder is adhered to the surface of the clay ball, sintered at 1250 ° C into 2mm diameter titanium oxide balls, mixed with alginic acid containing 25% water, put into a sealed container, and passed in oxygen, using visible light or Ultraviolet light was irradiated for 20 hours to obtain oligomeric alginic acid.
  • 10% potassium hydroxide aqueous solution was added to neutralize it to a pH of about 7.3, and an appropriate amount of water was added to prepare a potassium alginate solution.
  • ZBS1 and NF4040 nanofiltration membranes were used to repeat the ultra-thin Filtration and nanofiltration membrane operations, precipitation with 95% ethanol equivalent to twice the volume of the product, and drying to obtain potassium alginate with an average molecular weight of 7000, titanium oxide pellets can be recycled and reused.
  • the alginic acid raw material is oxidatively degraded by 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 ⁇ 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 nanofiltration membranes of the previous examples were repeated using ZBS1 and F4040 nanofiltration membranes. This operation yielded sodium alginate having an average molecular weight of 8000.
  • a 5% calcium chloride aqueous solution was added to obtain an insoluble alginic acid precipitate, which was washed with distilled water, and the generated hydrochloric acid was removed to bring the pH close to neutral and dry.
  • Example 18 Preparation method of chromium-containing alginate-The procedure of Example 17 was repeated, except that the calcium chloride solution was replaced with a trivalent chromium ion solution such as chromium trichloride.
  • 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 to make each tablet weigh 0.7 g and take 4 tablets daily.
  • Capsules, granules and tablets are recommended after meals.
  • Low molecular weight potassium alginate can treat hyperaldosteronism associated with hypertension.
  • radioimmunoassay kits Ten subjects are now provided. Using radioimmunoassay kits, the plasma aldosterone levels of these ten subjects before and after taking low molecular weight potassium alginate were measured. Ordinary diet, standing blood test. The alginate granules were orally administered in an amount of 6-8 g twice daily, and after 15 consecutive days of administration, the levels of aldosterone in the plasma before and after the administration were measured by radioimmunoassay (RIA).
  • 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
  • the average reduction was 63ng / L.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Polymers & Plastics (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Materials Engineering (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne un acide alginique ou ses sels présentant un poids moléculaire moyen compris entre 5.000 et 20.000 daltons et faisant preuve d'une viscosité intrinsèque d'environ 1 à 20 selon le viscosimètre d'Ubbelohde. La plupart des alginates présentent un poids moléculaire compris entre 1.000 et 30.000 daltons. Ces alginates sont obtenus à partir d'un acide alginique à poids moléculaire élevé par le biais de la décomposition et de l'ultrafiltration et de la nanofiltration. L'invention trouve une application dans la prévention et le traitement de l'hypertension, de hyperaldostéronisme primaire et dans la réduction du taux de sucre dans le sang.
PCT/CN1999/000202 1999-11-30 1999-11-30 Alginate a faible poids moleculaire, son procede de preparation et ses applications WO2001040315A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/CN1999/000202 WO2001040315A1 (fr) 1999-11-30 1999-11-30 Alginate a faible poids moleculaire, son procede de preparation et ses applications
AU15027/00A AU1502700A (en) 1999-11-30 1999-11-30 The alginate having low molecular weight, methods of manufacturing it and its use
CA002430277A CA2430277A1 (fr) 1999-11-30 1999-11-30 Alginate a faible poids moleculaire, son procede de preparation et ses applications

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN1999/000202 WO2001040315A1 (fr) 1999-11-30 1999-11-30 Alginate a faible poids moleculaire, son procede de preparation et ses applications

Publications (3)

Publication Number Publication Date
WO2001040315A1 true WO2001040315A1 (fr) 2001-06-07
WO2001040315A9 WO2001040315A9 (fr) 2001-12-06
WO2001040315A8 WO2001040315A8 (fr) 2002-03-21

Family

ID=4575155

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN1999/000202 WO2001040315A1 (fr) 1999-11-30 1999-11-30 Alginate a faible poids moleculaire, son procede de preparation et ses applications

Country Status (3)

Country Link
AU (1) AU1502700A (fr)
CA (1) CA2430277A1 (fr)
WO (1) WO2001040315A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1310954C (zh) * 2003-04-15 2007-04-18 哈尔滨工程大学 海藻酸铬的制备方法
US20100256090A1 (en) * 2007-12-29 2010-10-07 Chuanxing YU Alginic Acid with Low Molecular Weight, Its Salts, Uses, Preparative Methods, Pharmaceutical Compositions and Foods
CN101104649B (zh) * 2006-07-12 2011-05-18 谭攸恒 一种海藻酸钾及其组合物
WO2016045308A1 (fr) * 2014-09-26 2016-03-31 大连雅威特生物技术股份有限公司 Utilisation d'une préparation d'un oligomère d'alginate de sodium dans des produits pharmaceutiques, des produits de soins de santé et des produits de sel
CN112037931A (zh) * 2020-07-15 2020-12-04 新疆维吾尔自治区人民医院 在疑似原发性醛固酮增多症中应用的醛固酮增多预测体系

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010187659A (ja) * 2009-01-20 2010-09-02 Kao Corp 精製アルギン酸又はその塩

Citations (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN85106125A (zh) * 1984-08-10 1986-07-02 麦克公司 制备固态，除草的双吡啶季盐组成物的方法
JPS63101302A (ja) * 1986-10-17 1988-05-06 Meiji Seika Kaisha Ltd 農作物の栽培方法
EP0269937A2 (fr) * 1986-11-24 1988-06-08 MEDIOLANUM FARMACEUTICI s.r.l. Procédé de préparation contrôlée de glycosaminoglycanes de bas poids moléculaire
JPS63214192A (ja) * 1987-03-03 1988-09-06 Meiji Seika Kaisha Ltd アルギン酸オリゴ糖の製造法
US4792452A (en) * 1987-07-28 1988-12-20 E. R. Squibb & Sons, Inc. Controlled release formulation
JPH02225422A (ja) * 1989-02-28 1990-09-07 Kimitsu Kagaku Kogyo Kk 薬剤組成物
JPH03273002A (ja) * 1990-03-22 1991-12-04 Otsuka Chem Co Ltd アルギン酸分解物
JPH04169188A (ja) * 1990-10-31 1992-06-17 Taiyo Fishery Co Ltd アルギン酸オリゴ糖の製造方法及び精製法
EP0493265A1 (fr) * 1990-12-28 1992-07-01 Sumitomo Metal Industries, Ltd. Aliments et boissons contenant de l'algine
JPH04335839A (ja) * 1991-05-09 1992-11-24 Meiji Seika Kaisha Ltd 植物の形態形成又は分化の促進方法
JPH0517315A (ja) * 1991-07-03 1993-01-26 Sankin Kogyo Kk 歯科用アルギン酸塩印象材組成物
GB2266532A (en) * 1992-04-28 1993-11-03 Taiyo Fishery Co Ltd Aliginate oligosaccharide and method for producing same
JPH05304974A (ja) * 1992-03-06 1993-11-19 Maruha Corp アルギン酸カルシウムオリゴ糖及びその製造法
CN1089619A (zh) * 1993-01-06 1994-07-20 山东烟台西苑制药厂 一种藻酸双酯钠的生产方法
JPH07147935A (ja) * 1993-11-26 1995-06-13 Meiji Seika Kaisha Ltd ダイエット・糖尿病用食品
JPH0881378A (ja) * 1994-07-14 1996-03-26 Maruha Corp ヒト表皮角化細胞賦活剤
CN1156150A (zh) * 1996-12-18 1997-08-06 谭攸恒 褐藻酸钾的制备方法及其应用
JPH1180204A (ja) * 1997-09-05 1999-03-26 Nikka Chem Co Ltd アルギン酸の加水分解方法および分解物
JPH11116415A (ja) * 1997-10-08 1999-04-27 Japan Atom Energy Res Inst 植物成長促進剤

Patent Citations (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN85106125A (zh) * 1984-08-10 1986-07-02 麦克公司 制备固态，除草的双吡啶季盐组成物的方法
JPS63101302A (ja) * 1986-10-17 1988-05-06 Meiji Seika Kaisha Ltd 農作物の栽培方法
EP0269937A2 (fr) * 1986-11-24 1988-06-08 MEDIOLANUM FARMACEUTICI s.r.l. Procédé de préparation contrôlée de glycosaminoglycanes de bas poids moléculaire
JPS63214192A (ja) * 1987-03-03 1988-09-06 Meiji Seika Kaisha Ltd アルギン酸オリゴ糖の製造法
US4792452A (en) * 1987-07-28 1988-12-20 E. R. Squibb & Sons, Inc. Controlled release formulation
JPH02225422A (ja) * 1989-02-28 1990-09-07 Kimitsu Kagaku Kogyo Kk 薬剤組成物
JPH03273002A (ja) * 1990-03-22 1991-12-04 Otsuka Chem Co Ltd アルギン酸分解物
JPH04169188A (ja) * 1990-10-31 1992-06-17 Taiyo Fishery Co Ltd アルギン酸オリゴ糖の製造方法及び精製法
EP0493265A1 (fr) * 1990-12-28 1992-07-01 Sumitomo Metal Industries, Ltd. Aliments et boissons contenant de l'algine
JPH04335839A (ja) * 1991-05-09 1992-11-24 Meiji Seika Kaisha Ltd 植物の形態形成又は分化の促進方法
JPH0517315A (ja) * 1991-07-03 1993-01-26 Sankin Kogyo Kk 歯科用アルギン酸塩印象材組成物
JPH05304974A (ja) * 1992-03-06 1993-11-19 Maruha Corp アルギン酸カルシウムオリゴ糖及びその製造法
GB2266532A (en) * 1992-04-28 1993-11-03 Taiyo Fishery Co Ltd Aliginate oligosaccharide and method for producing same
CN1089619A (zh) * 1993-01-06 1994-07-20 山东烟台西苑制药厂 一种藻酸双酯钠的生产方法
JPH07147935A (ja) * 1993-11-26 1995-06-13 Meiji Seika Kaisha Ltd ダイエット・糖尿病用食品
JPH0881378A (ja) * 1994-07-14 1996-03-26 Maruha Corp ヒト表皮角化細胞賦活剤
CN1156150A (zh) * 1996-12-18 1997-08-06 谭攸恒 褐藻酸钾的制备方法及其应用
JPH1180204A (ja) * 1997-09-05 1999-03-26 Nikka Chem Co Ltd アルギン酸の加水分解方法および分解物
JPH11116415A (ja) * 1997-10-08 1999-04-27 Japan Atom Energy Res Inst 植物成長促進剤

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1310954C (zh) * 2003-04-15 2007-04-18 哈尔滨工程大学 海藻酸铬的制备方法
CN101104649B (zh) * 2006-07-12 2011-05-18 谭攸恒 一种海藻酸钾及其组合物
US20100256090A1 (en) * 2007-12-29 2010-10-07 Chuanxing YU Alginic Acid with Low Molecular Weight, Its Salts, Uses, Preparative Methods, Pharmaceutical Compositions and Foods
US8686053B2 (en) * 2007-12-29 2014-04-01 Chuanxing YU Alginic acid with low molecular weight, its salts, uses, preparative methods, pharmaceutical compositions and foods
WO2016045308A1 (fr) * 2014-09-26 2016-03-31 大连雅威特生物技术股份有限公司 Utilisation d'une préparation d'un oligomère d'alginate de sodium dans des produits pharmaceutiques, des produits de soins de santé et des produits de sel
CN112037931A (zh) * 2020-07-15 2020-12-04 新疆维吾尔自治区人民医院 在疑似原发性醛固酮增多症中应用的醛固酮增多预测体系
CN112037931B (zh) * 2020-07-15 2023-10-20 新疆维吾尔自治区人民医院 在疑似原发性醛固酮增多症中应用的醛固酮增多预测体系

Also Published As

Publication number Publication date
AU1502700A (en) 2001-06-12
WO2001040315A9 (fr) 2001-12-06
WO2001040315A8 (fr) 2002-03-21
CA2430277A1 (fr) 2001-07-06

Similar Documents

Publication Publication Date Title
US8686053B2 (en) Alginic acid with low molecular weight, its salts, uses, preparative methods, pharmaceutical compositions and foods
Tolstikova et al. The complexes of drugs with carbohydrate-containing plant metabolites as pharmacologically promising agents
JP5759655B2 (ja) 微結晶セルロースの製造方法
Nayak et al. Gelled microparticles/beads of sterculia gum and tamarind gum for sustained drug release
JP5723787B2 (ja) 制御放出の製剤処方または食品処方およびその製造方法
CA2675117C (fr) Complexes fer-hydrate de carbone comportant au moins 2 % en poids de fer total sous forme de fer (ii)
TW200528475A (en) Polysaccharide containing chitosan, manufacture and usage thereof
Gorbunova et al. Alginate-based encapsulation of extracts from beta Vulgaris cv. beet greens: Stability and controlled release under simulated gastrointestinal conditions
CN109350607B (zh) 包覆魔芋葡甘露聚糖的nadh纳米微球及其制备工艺与应用
JP7220670B2 (ja) オゾンを用いた多糖類の分解方法
JP2006516988A (ja) 持続した薬物放出またはムコ粘着のための活性剤およびキトサンを含む製薬組成物
JPH11507406A (ja) 改善された医薬的付形剤としての精製されたガラクトマンナン
JP2007332336A (ja) メタボリックシンドローム治療剤
CN106420668B (zh) 一种淀粉基控缓释载体材料及其制备方法与应用
WO2001040315A1 (fr) Alginate a faible poids moleculaire, son procede de preparation et ses applications
WO1998025481A1 (fr) Composition d'ail fermente
CN1157415C (zh) 低分子量藻酸盐及其制备方法和用途
CN116271200A (zh) 用于糖尿病溃疡的纳米复合创面修复凝胶及其制备方法
IL206124A (en) The slowly released composition based on the association of glycogen and alginate
CN112315922B (zh) 一种西咪替丁片的制备方法
CN111217934B (zh) 一种去除果胶中内毒素的方法和去除内毒素的果胶
WO2009011520A2 (fr) Nanoparticules contenant du calcium et leur procédé de production
CN1102153C (zh) 水溶性壳聚糖的制备方法
JP2007533619A (ja) チラコイドエキスを送達するための経口用組成物および経口投与経路
CN111050779A (zh) 血糖值尖峰抑制剂、食品及血糖值尖峰抑制剂的制造方法

Legal Events

Date Code Title Description
ENP Entry into the national phase

Ref country code: AU

Ref document number: 2000 15027

Kind code of ref document: A

Format of ref document f/p: F

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: C2

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: C2

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

COP Corrected version of pamphlet

Free format text: PAGE 12, CLAIMS, ADDED

AK Designated states

Kind code of ref document: C1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: C1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

CFP Corrected version of a pamphlet front page

Free format text: UNDER (71) THE NAME AND ITS TRANSLITERATION IN CHINESE CORRECTED

WWE Wipo information: entry into national phase

Ref document number: 998169315

Country of ref document: CN

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
WWE Wipo information: entry into national phase

Ref document number: 2430277

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 10399742

Country of ref document: US