US20020115639A1 - Glucosamine and method of making glucosamine from microbial blomass - Google Patents
Glucosamine and method of making glucosamine from microbial blomass Download PDFInfo
- Publication number
- US20020115639A1 US20020115639A1 US09/785,695 US78569501A US2002115639A1 US 20020115639 A1 US20020115639 A1 US 20020115639A1 US 78569501 A US78569501 A US 78569501A US 2002115639 A1 US2002115639 A1 US 2002115639A1
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- Prior art keywords
- glucosamine
- containing material
- percent
- biomass
- chitin
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- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 title claims abstract description 136
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 title claims abstract description 135
- 229960002442 glucosamine Drugs 0.000 title claims abstract description 134
- 230000000813 microbial effect Effects 0.000 title claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 title description 10
- 239000002028 Biomass Substances 0.000 claims abstract description 66
- 230000002538 fungal effect Effects 0.000 claims abstract description 29
- 229920002101 Chitin Polymers 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 22
- 238000005903 acid hydrolysis reaction Methods 0.000 claims abstract description 11
- 239000007858 starting material Substances 0.000 claims abstract description 8
- 241000228257 Aspergillus sp. Species 0.000 claims abstract description 6
- 241001558145 Mucor sp. Species 0.000 claims abstract description 6
- 241000228168 Penicillium sp. Species 0.000 claims abstract description 6
- 241001465754 Metazoa Species 0.000 claims abstract description 4
- 239000000463 material Substances 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 20
- 239000000243 solution Substances 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
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- 239000008103 glucose Substances 0.000 claims description 8
- 239000003929 acidic solution Substances 0.000 claims description 6
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- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical class N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
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- CBOJBBMQJBVCMW-BTVCFUMJSA-N (2r,3r,4s,5r)-2-amino-3,4,5,6-tetrahydroxyhexanal;hydrochloride Chemical class Cl.O=C[C@H](N)[C@@H](O)[C@H](O)[C@H](O)CO CBOJBBMQJBVCMW-BTVCFUMJSA-N 0.000 description 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
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- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
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- 206010061218 Inflammation Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
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- FLEAADSSUQORCN-WBQOVJPJSA-N N-[(2R,3R,4S,5R)-3,4,5,6-tetrahydroxy-1-oxohexan-2-yl]acetamide N-[(3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O FLEAADSSUQORCN-WBQOVJPJSA-N 0.000 description 1
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- 241000582914 Saccharomyces uvarum Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- CDOJPCSDOXYJJF-SSRMKSSXSA-N [H]O[C@@H]1O[C@@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2NC(C)=O)[C@@H](O)[C@@H]1NC(C)=O Chemical compound [H]O[C@@H]1O[C@@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2NC(C)=O)[C@@H](O)[C@@H]1NC(C)=O CDOJPCSDOXYJJF-SSRMKSSXSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- FZHXIRIBWMQPQF-SLPGGIOYSA-N aldehydo-D-glucosamine Chemical compound O=C[C@H](N)[C@@H](O)[C@H](O)[C@H](O)CO FZHXIRIBWMQPQF-SLPGGIOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000002009 allergenic effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
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- 210000000845 cartilage Anatomy 0.000 description 1
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- 239000000356 contaminant Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000909 electrodialysis Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 150000002303 glucose derivatives Chemical group 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/04—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen
- C07H5/06—Aminosugars
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
-
- 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
- the present invention is directed to glucosamine compositions and to methods of making glucosamine compositions.
- Glucosamine is a nutraceutical supplement that has been shown to provide significant therapeutic relief for arthritis and joint pain. Although the mechanism is not entirely known, it is believed that glucosamine functions to aid in restoration of the cartilage to relieve inflammation in the joints, thereby providing significant benefit to patients.
- glucosamine is primarily derived from harvested natural sources, such as shellfish and other aquatic organisms. Components of the shell or exoskeleton of these organisms are converted into glucosamine using various production techniques. These natural sources are acceptable for producing glucosamine for some applications, but they have limitations. These limitations include the fact that wild shellfish can have significant variations in their composition because they grow naturally under uncontrolled circumstances. The shellfish can vary in such aspects as their size and composition depending upon the growing conditions as well as their species. Also, without control over the growing conditions, the shellfish can be exposed to environmental contaminants, including heavy metals, that can be retained in glucosamine or other products produced from the shellfish. Shellfish harvests are often seasonal, and thus the supply and price of shellfish shows significant variation over time.
- glucosamine derived from shellfish A further concern with glucosamine derived from shellfish is that significant portions of the human population have shellfish allergies and are unable to use products that contain ingredients derived from shellfish. Highly processed materials, such as glucosamine, do not necessarily provide any allergic risk when prepared properly; but a concern remains that hyper allergenic individuals will still be allergic to even minute traces of allergens present from the original shellfish. Even if no such allergens are present, glucosamine derived from shellfish can pose a concern to individuals who are allergic to shellfish because individual consumers are not necessarily aware of whether or not all of the allergens have been removed.
- the present invention is directed to glucosamine, including glucosamine-containing material suitable for human or animal consumption.
- Glucosamine of the present invention is derived from fermented fungal biomass containing chitin. Suitable starting materials include substantially uniform microbial fungal sources, such as fungal sources derived from Aspergillus sp., Penicillium sp., Mucor sp., and combinations thereof. Use of a fungal biomass results in a high quality product that produces generally uniform glucosamine having low levels of impurities.
- the glucosamine of the present invention normally has relatively low ash content, and low heavy metal content. In addition, as a product of fungal biomass, the glucosamine does not pose a hazard to persons who have shellfish allergies.
- the present invention is also directed to methods of producing glucosamine by acid hydrolysis of fermented fungal biomass.
- the methods of obtaining glucosamine from microbial biomass include reacting chitin-containing biomass in an acidic solution, in particular reacting the chitin-containing biomass in acid at an elevated temperature.
- FIG. 1 is chart showing the percent yield of glucosamine over time of an example method of making glucosamine in accordance with the invention.
- FIG. 2 is a chromatogram of glucosamine made in accordance with the invention.
- FIG. 3 is a chromatogram of glucosamine made in accordance with the invention.
- the present invention is directed to glucosamine, including glucosamine-containing material suitable for human or animal consumption.
- the glucosamine is derived from chitin present in various types of fungal biomass.
- Chitin is a natural polysaccharide, with the structure of an unbranched polymer of 2-acetoamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine). This formula can be represented by the general repeating structure:
- Chitin is typically an amorphous solid that is largely insoluble in water, dilute acids, and alkali. Although chitin has various commercial applications, greater commercial utility can be found by transforming the polymeric structure into individual components of 2-amino-2-deoxy-D-glucose, which is known as glucosamine. Structurally, glucosamine is modified glucose with an amine group replacing the OH group found on carbon two (C-2). The general structure is:
- glucosamine of the present invention is derived from fermented fungal biomass containing chitin.
- suitable starting materials include substantially uniform microbial fungal sources, such as fungal sources derived from Aspergillus sp., Penicillium sp., Mucor sp. and combinations thereof.
- Use of a fungal biomass results in a high quality product that produces a generally uniform glucosamine having low levels of impurities.
- the glucosamine of the present invention normally has relatively low ash content, and low heavy metals content.
- the glucosamine does not pose a hazard to persons who have shellfish allergies.
- the glucosamine of the present invention is derived from relatively uniform fungal biomass sources, and thus typically has a generally uniform composition.
- the resulting glucosamine containing composition can be produced with varying levels of purity, including compositions that exceed 95 percent purity, 98 percent purity, and even 99.8 percent purity.
- the glucosamine compositions can also contain additional ingredients, such as additional salts. In such circumstances the overall purity of the desired composition relative to undesirable impurities can be maintained at levels that exceed 95 percent purity, 98 percent purity, and even 99.8 percent purity.
- the glucosamine of the present invention has the general formula represented below:
- glucosamine refers to the various forms of glucosamine, including salt complexes and substituted glucosamine.
- the glucosamine is normally of high purity, but can contain other ingredients, including glucose, unreacted chitin, and other materials.
- the glucosamine contains less than 10 percent glucose, more preferably less than 5 percent glucose, and even more preferably less than 2 percent glucose.
- the glucosamine of the present invention has a relatively low ash content.
- the ash content is usually less than 5 percent, more typically less than 2 percent, and can even be less than 1 percent in some implementations.
- Heavy metal content is normally similarly low, typically well below 100 parts per million, more typically below 50 parts per million, even more typically below 20 parts per million. In certain embodiments this level is below 10 parts per million.
- the glucosamine can have a positive specific rotation, such as a positive 69 to 74 degree specific rotation for the glucosamine hydrochloride salt.
- the glucosamine of the invention is usually relatively white in its purified dry form, but colorless when dissolved in an aqueous solution.
- a 20 percent by weight solution of the glucosamine has an American Public Health Association (APHA) color of less than 50.
- APHA American Public Health Association
- Suitable starting materials include substantially uniform microbial biomass sources, typically fungal biomass, such as filamentous fungi having greater than 10 percent chitin by total dry cell weight, such as fungal sources derived from Aspergillus sp., Penicillium sp., Mucor sp.
- Suitable fungal biomasses include Aspergillus niger, Aspergillus terreus, Aspergillus oryzae, Mucor rouxii, Penicillium chrysogenum, Penicillium notatum, Saccharomyces cerevisiae; Saccharomyces uvarum; and in particular Candida guillermondi, Aspergillus niger, and Aspergillus terreus.
- the biomass is usually recovered from a commercial fermentation reaction, such as the commercial production of organic acids, including citric acid. Also, the biomass suitable for production of glucosamine can be generated specifically for this process and not as a byproduct of other processes.
- microbial does not include phyto-plankton and crustaceans or mollusks.
- the invention is particularly well suited to uses where the chitin levels in the biomass exceed 5 percent of the dry biomass weight.
- Such biomass usually has between 5 and 25 percent chitin, and can have from 10 to 20 percent chitin, based upon dry weight of the biomass.
- the microbial biomass be produced in a substantially controlled manner having relatively uniform temperature and nutrient levels during the growth of the biomass.
- the present invention is also directed to methods of forming glucosamine, including formation from acid hydrolysis of fermented fungal biomass.
- the acid hydrolysis breaks the ether linkages and deacetylates the chitin molecule to generate free glucosamine.
- Acid hydrolysis is strong enough to break the chitin into glucosamine, but leaves the glucosamine molecule substantially intact.
- the hydrolysis reaction conditions have the added advantage of breaking down some of the other components (such glucans, proteins, and lipids) that exist in the fungal biomass.
- such acid hydrolysis is performed by treating the fungal biomass for greater than 4 hours in a strong acid solution.
- Glucosamine production usually includes the steps of providing chitin-containing biomass, reacting the chitin-containing biomass in an acidic solution to form glucosamine, and separating the glucosamine from the acidic solution.
- the reaction typically has a yield of glucosamine of greater than 50 percent of total chitin content of the fungal biomass starting material.
- Strong acids can be used to hydrolyze the fungal biomass, including acids of concentrations less than 50 percent, and more commonly from 5 to 25 percent. Suitable strong acids include hydrochloric, sulfuric, phosphoric, and citric acid at appropriate levels.
- the glucosamine forming reaction is normally conducted with 5 to 20 percent acid, 2 to 50 percent pretreated biomass (based upon dry weight, although the biomass is typically processed with water present), and 35 to 93 percent water.
- the reaction mixture comprises from 8 to 12 percent hydrochloric acid, from 4 to 8 percent biomass (based upon dry weight), and from 80 to 90 percent water.
- the mixture containing the biomass, acid, and water is heated and maintained at an elevated temperature.
- the mixture is usually heated to a temperature at or near its boiling point and maintained under reflux conditions for greater than 5 hours, more typically greater than 8 hours, and usually less than 16 hours. It is desirable to have the reaction continue long enough to have a complete breakdown of the chitin, but not take so long as to be inefficient or to excessively decompose the glucosamine.
- a first purification step normally includes filtration to remove particulate impurities, resulting in a substantially clear filtrate.
- This filtrate normally contains glucosamine, as well as small quantities of glucose and other sugars.
- An evaporative step can subsequently be performed to concentrate the glucosamine and possibly remove some of the acid, which can be recycled and reused.
- the mixture can be concentrated by evaporation, and the glucosamine can be precipitated out as purified solids by either adding ethanol to the concentrated mixture or continuing the evaporation to its solubility limits.
- the glucosamine can be recovered by filtration or centrifugation, followed by drying.
- the dried glucosamine is optionally further purified to remove any residual sugar.
- One method of removing these excess sugars is by dissolving the glucosamine in water and adding ethanol, which precipitates the glucosamine at greater purity.
- the solution can be purified by electro dialysis, chromatography, membrane filtration, etc.
- the glucosamine is optionally decolorized with ethanol, carbon, or other suitable material and method.
- the biomass can initially be treated to remove some impurities or to improve glucosamine production.
- treatments can include heating the biomass, adding digestive enzymes, mixing with an acid or base, mechanical agitation, or dewatering by compression.
- One particularly suitable treatment is pretreating the biomass in the presence of sodium hydroxide.
- a concentration of less than 10 percent sodium hydroxide is added to the fungal biomass, which is heated to an elevated temperature for a period sufficient to remove a considerable portion of the non-chitin containing material. This period is normally less than two hours.
- This pretreatment method requires heating the fungal biomass to 100 to 125° C. in a 2 to 8 percent solution of sodium hydroxide for 20 to 60 minutes.
- This step hydrolyzes some protein and glucan in the biomass, the byproducts of which are optionally removed by filtration.
- the filtration step is followed to remove soluble proteins, amino acids, etc.
- the washed and pretreated biomass contains greater than 50 percent water, and even greater than 70 or 80 percent water. Typically the water level is from about 80 to 95 percent for this prewashed fungal biomass.
- Citric biomass was pretreated with a 4 percent aqueous sodium hydroxide (NaOH) solution in an autoclave at 120° C. for 1 hour. This step removed excess proteins and other undesirable materials.
- the biomass was then thoroughly washed with de-ionized water until its pH was approximately 7.0. This washed material was mixed with concentrated hydrochloric acid (HCl) and water to form a mixture of 10 to 15 percent HCl and 5 to 6 percent biomass, based upon dry weight of the biomass. This mixture was heated at reflux. Samples were taken from time to time, and the reaction analyzed with a high-pressure liquid chromatograph available from Dionex HPLC under the trade designation “DX-500”.
- FIG. 1 shows a chart indicating glucosamine production, and shows that the glucosamine was increasingly produced as the reaction ran through 8 hours, but that the amount of glucose diminished after 4 hours. After 8 hours the glucosamine produced in the yield of 14 percent.
- FIG. 2 shows a chart indicating glucosamine production, and shows that the glucosamine was increasingly produced as the reaction ran through 8 hours, but that the amount of glucose diminished after 4 hours. After 8 hours the glucosamine produced in the yield of 14 percent.
- a chromatogram of the product is shown in FIG. 2.
- Example 1 was repeated, but the pretreated biomass was maintained under reflux conditions for 13 hours. The resulting glucosamine was greater than 98 percent pure.
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Abstract
Description
- The present invention is directed to glucosamine compositions and to methods of making glucosamine compositions.
- Glucosamine is a nutraceutical supplement that has been shown to provide significant therapeutic relief for arthritis and joint pain. Although the mechanism is not entirely known, it is believed that glucosamine functions to aid in restoration of the cartilage to relieve inflammation in the joints, thereby providing significant benefit to patients.
- Presently, glucosamine is primarily derived from harvested natural sources, such as shellfish and other aquatic organisms. Components of the shell or exoskeleton of these organisms are converted into glucosamine using various production techniques. These natural sources are acceptable for producing glucosamine for some applications, but they have limitations. These limitations include the fact that wild shellfish can have significant variations in their composition because they grow naturally under uncontrolled circumstances. The shellfish can vary in such aspects as their size and composition depending upon the growing conditions as well as their species. Also, without control over the growing conditions, the shellfish can be exposed to environmental contaminants, including heavy metals, that can be retained in glucosamine or other products produced from the shellfish. Shellfish harvests are often seasonal, and thus the supply and price of shellfish shows significant variation over time.
- A further concern with glucosamine derived from shellfish is that significant portions of the human population have shellfish allergies and are unable to use products that contain ingredients derived from shellfish. Highly processed materials, such as glucosamine, do not necessarily provide any allergic risk when prepared properly; but a concern remains that hyper allergenic individuals will still be allergic to even minute traces of allergens present from the original shellfish. Even if no such allergens are present, glucosamine derived from shellfish can pose a concern to individuals who are allergic to shellfish because individual consumers are not necessarily aware of whether or not all of the allergens have been removed.
- An additional problem associated with existing sources of shellfish-derived glucosamine is that some of the shellfish supply is harvested from the seas and oceans of the world. Excessive harvest of shellfish could have a great negative environmental impact. Thus, it is believed that some consumers would prefer to use glucosamine that is not harvested at the expense of sea life. Even if the environmental impact of harvesting shellfish is not negative, there remains concern that the supply of wild shellfish is limited in quantity and inconsistent in quantity from year to year.
- Therefore, a need exists for a source of safe, consistent, high quality glucosamine that can be created economically and with a minimum of environmental impact.
- The present invention is directed to glucosamine, including glucosamine-containing material suitable for human or animal consumption. Glucosamine of the present invention is derived from fermented fungal biomass containing chitin. Suitable starting materials include substantially uniform microbial fungal sources, such as fungal sources derived from Aspergillus sp., Penicillium sp., Mucor sp., and combinations thereof. Use of a fungal biomass results in a high quality product that produces generally uniform glucosamine having low levels of impurities. The glucosamine of the present invention normally has relatively low ash content, and low heavy metal content. In addition, as a product of fungal biomass, the glucosamine does not pose a hazard to persons who have shellfish allergies.
- The present invention is also directed to methods of producing glucosamine by acid hydrolysis of fermented fungal biomass. The methods of obtaining glucosamine from microbial biomass include reacting chitin-containing biomass in an acidic solution, in particular reacting the chitin-containing biomass in acid at an elevated temperature.
- Other features and advantages of the invention will be apparent from the following detailed description of the invention and the claims. The above summary of principles of the disclosure is not intended to describe each illustrated embodiment or every implementation of the present disclosure. The detailed description that follows more particularly exemplifies certain embodiments utilizing the principles disclosed herein.
- The invention will be more fully explained with reference to the following drawings, in which:
- FIG. 1 is chart showing the percent yield of glucosamine over time of an example method of making glucosamine in accordance with the invention.
- FIG. 2 is a chromatogram of glucosamine made in accordance with the invention.
- FIG. 3 is a chromatogram of glucosamine made in accordance with the invention.
- While principles of the invention are amenable to various modifications and alternative forms, specifics thereof have been shown by way of example and will be described in detail. It should be understood, however, that the intention is not to limit the invention to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the disclosure.
- The present invention is directed to glucosamine, including glucosamine-containing material suitable for human or animal consumption. The glucosamine is derived from chitin present in various types of fungal biomass. Chitin is a natural polysaccharide, with the structure of an unbranched polymer of 2-acetoamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine). This formula can be represented by the general repeating structure:
- Chitin is typically an amorphous solid that is largely insoluble in water, dilute acids, and alkali. Although chitin has various commercial applications, greater commercial utility can be found by transforming the polymeric structure into individual components of 2-amino-2-deoxy-D-glucose, which is known as glucosamine. Structurally, glucosamine is modified glucose with an amine group replacing the OH group found on carbon two (C-2). The general structure is:
- As stated above, glucosamine of the present invention is derived from fermented fungal biomass containing chitin. Suitable starting materials include substantially uniform microbial fungal sources, such as fungal sources derived from Aspergillus sp., Penicillium sp., Mucor sp. and combinations thereof. Use of a fungal biomass results in a high quality product that produces a generally uniform glucosamine having low levels of impurities. The glucosamine of the present invention normally has relatively low ash content, and low heavy metals content. In addition, as a product of fungal biomass, the glucosamine does not pose a hazard to persons who have shellfish allergies.
- The glucosamine composition, starting materials, and production methods will now be described in greater detail.
- A. Glucosamine
- The glucosamine of the present invention is derived from relatively uniform fungal biomass sources, and thus typically has a generally uniform composition. Depending upon the methodology used to purify the glucosamine or desired glucosamine salt; the resulting glucosamine containing composition can be produced with varying levels of purity, including compositions that exceed 95 percent purity, 98 percent purity, and even 99.8 percent purity. The glucosamine compositions can also contain additional ingredients, such as additional salts. In such circumstances the overall purity of the desired composition relative to undesirable impurities can be maintained at levels that exceed 95 percent purity, 98 percent purity, and even 99.8 percent purity.
-
- This general formula can vary depending upon the presence of various salts of the glucosamine, including citrate, acetate, phosphate, sulfate, chloride, lactate, gluconate, etc. Also, the glucosamine can be substituted or modified without diverging from the scope of the invention. Thus, as used herein, the term glucosamine refers to the various forms of glucosamine, including salt complexes and substituted glucosamine.
- The glucosamine is normally of high purity, but can contain other ingredients, including glucose, unreacted chitin, and other materials. Preferably the glucosamine contains less than 10 percent glucose, more preferably less than 5 percent glucose, and even more preferably less than 2 percent glucose.
- The glucosamine of the present invention has a relatively low ash content. The ash content is usually less than 5 percent, more typically less than 2 percent, and can even be less than 1 percent in some implementations. Heavy metal content is normally similarly low, typically well below 100 parts per million, more typically below 50 parts per million, even more typically below 20 parts per million. In certain embodiments this level is below 10 parts per million. The glucosamine can have a positive specific rotation, such as a positive 69 to 74 degree specific rotation for the glucosamine hydrochloride salt.
- The glucosamine of the invention is usually relatively white in its purified dry form, but colorless when dissolved in an aqueous solution. In one example, a 20 percent by weight solution of the glucosamine has an American Public Health Association (APHA) color of less than 50.
- B. Microbial Fungal Biomass Starting Materials
- Suitable starting materials include substantially uniform microbial biomass sources, typically fungal biomass, such as filamentous fungi having greater than 10 percent chitin by total dry cell weight, such as fungal sources derived from Aspergillus sp., Penicillium sp., Mucor sp. Suitable fungal biomasses includeAspergillus niger, Aspergillus terreus, Aspergillus oryzae, Mucor rouxii, Penicillium chrysogenum, Penicillium notatum, Saccharomyces cerevisiae; Saccharomyces uvarum; and in particular Candida guillermondi, Aspergillus niger, and Aspergillus terreus. The biomass is usually recovered from a commercial fermentation reaction, such as the commercial production of organic acids, including citric acid. Also, the biomass suitable for production of glucosamine can be generated specifically for this process and not as a byproduct of other processes. As used herein, the term microbial does not include phyto-plankton and crustaceans or mollusks.
- The invention is particularly well suited to uses where the chitin levels in the biomass exceed 5 percent of the dry biomass weight. Such biomass usually has between 5 and 25 percent chitin, and can have from 10 to 20 percent chitin, based upon dry weight of the biomass. Also, in order to prepare the highest quality glucosamine, it is sometimes desirable that the microbial biomass be produced in a substantially controlled manner having relatively uniform temperature and nutrient levels during the growth of the biomass.
- C. Glucosamine Production Methods
- The present invention is also directed to methods of forming glucosamine, including formation from acid hydrolysis of fermented fungal biomass. The acid hydrolysis breaks the ether linkages and deacetylates the chitin molecule to generate free glucosamine. Acid hydrolysis is strong enough to break the chitin into glucosamine, but leaves the glucosamine molecule substantially intact. The hydrolysis reaction conditions have the added advantage of breaking down some of the other components (such glucans, proteins, and lipids) that exist in the fungal biomass. Typically, such acid hydrolysis is performed by treating the fungal biomass for greater than 4 hours in a strong acid solution.
- Glucosamine production usually includes the steps of providing chitin-containing biomass, reacting the chitin-containing biomass in an acidic solution to form glucosamine, and separating the glucosamine from the acidic solution. The reaction typically has a yield of glucosamine of greater than 50 percent of total chitin content of the fungal biomass starting material.
- Strong acids can be used to hydrolyze the fungal biomass, including acids of concentrations less than 50 percent, and more commonly from 5 to 25 percent. Suitable strong acids include hydrochloric, sulfuric, phosphoric, and citric acid at appropriate levels.
- The glucosamine forming reaction is normally conducted with 5 to 20 percent acid, 2 to 50 percent pretreated biomass (based upon dry weight, although the biomass is typically processed with water present), and 35 to 93 percent water. In certain implementations the reaction mixture comprises from 8 to 12 percent hydrochloric acid, from 4 to 8 percent biomass (based upon dry weight), and from 80 to 90 percent water.
- The mixture containing the biomass, acid, and water is heated and maintained at an elevated temperature. The mixture is usually heated to a temperature at or near its boiling point and maintained under reflux conditions for greater than 5 hours, more typically greater than 8 hours, and usually less than 16 hours. It is desirable to have the reaction continue long enough to have a complete breakdown of the chitin, but not take so long as to be inefficient or to excessively decompose the glucosamine.
- Reaction in the acid solution produces glucosamine, but subsequent purification steps are typically necessary to produce a satisfactory product. A first purification step normally includes filtration to remove particulate impurities, resulting in a substantially clear filtrate. This filtrate normally contains glucosamine, as well as small quantities of glucose and other sugars. An evaporative step can subsequently be performed to concentrate the glucosamine and possibly remove some of the acid, which can be recycled and reused. The mixture can be concentrated by evaporation, and the glucosamine can be precipitated out as purified solids by either adding ethanol to the concentrated mixture or continuing the evaporation to its solubility limits.
- The glucosamine can be recovered by filtration or centrifugation, followed by drying. The dried glucosamine is optionally further purified to remove any residual sugar. One method of removing these excess sugars is by dissolving the glucosamine in water and adding ethanol, which precipitates the glucosamine at greater purity. Alternatively, the solution can be purified by electro dialysis, chromatography, membrane filtration, etc. The glucosamine is optionally decolorized with ethanol, carbon, or other suitable material and method.
- In addition to the steps described above, the biomass can initially be treated to remove some impurities or to improve glucosamine production. These treatments can include heating the biomass, adding digestive enzymes, mixing with an acid or base, mechanical agitation, or dewatering by compression. One particularly suitable treatment is pretreating the biomass in the presence of sodium hydroxide. In certain implementations a concentration of less than 10 percent sodium hydroxide is added to the fungal biomass, which is heated to an elevated temperature for a period sufficient to remove a considerable portion of the non-chitin containing material. This period is normally less than two hours. One specific example of this pretreatment method requires heating the fungal biomass to 100 to 125° C. in a 2 to 8 percent solution of sodium hydroxide for 20 to 60 minutes. This step hydrolyzes some protein and glucan in the biomass, the byproducts of which are optionally removed by filtration. The filtration step is followed to remove soluble proteins, amino acids, etc. In specific implementations of the invention, the washed and pretreated biomass contains greater than 50 percent water, and even greater than 70 or 80 percent water. Typically the water level is from about 80 to 95 percent for this prewashed fungal biomass.
- The invention will be further explained by the following non-limiting illustrative examples. Unless otherwise indicated, all amounts are expressed in parts by weight.
- Citric biomass was pretreated with a 4 percent aqueous sodium hydroxide (NaOH) solution in an autoclave at 120° C. for 1 hour. This step removed excess proteins and other undesirable materials. The biomass was then thoroughly washed with de-ionized water until its pH was approximately 7.0. This washed material was mixed with concentrated hydrochloric acid (HCl) and water to form a mixture of 10 to 15 percent HCl and 5 to 6 percent biomass, based upon dry weight of the biomass. This mixture was heated at reflux. Samples were taken from time to time, and the reaction analyzed with a high-pressure liquid chromatograph available from Dionex HPLC under the trade designation “DX-500”.
- The results are provided in FIG. 1, which shows a chart indicating glucosamine production, and shows that the glucosamine was increasingly produced as the reaction ran through 8 hours, but that the amount of glucose diminished after 4 hours. After 8 hours the glucosamine produced in the yield of 14 percent. A chromatogram of the product is shown in FIG. 2.
- Following reaction, the mixture was filtered, and the filtrate evaporated using a rotating evaporator manufactured by RotaVap to increase the glucosamine concentration of the solution. The final volume was reduced to about 10 to 20 ml. To this solution was added 20 ml of ethanol and the solution swirled to promote precipitation of glucosamine and enhance yield. These glucosamine precipitates were obtained by filtration and were further washed with alcohol until the color became white. FIG. 3 shows a chromatogram of the product, indicating greater than 97 percent glucosamine.
- Example 1 was repeated, but the pretreated biomass was maintained under reflux conditions for 13 hours. The resulting glucosamine was greater than 98 percent pure.
- The foregoing detailed description and examples have been given for clarity of understanding only. No unnecessary limitations are to be understood from this description or examples. The invention is not limited to the exact details shown and described, for variations will be included within the invention defined by the claims.
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AT02742474T ATE493502T1 (en) | 2001-02-16 | 2002-02-15 | GLUCOSAMINE AND METHOD FOR PRODUCING GLUCOSAMINE FROM MICROBIAL BIOMASS |
BR0207287-4A BR0207287A (en) | 2001-02-16 | 2002-02-15 | Glycosamine and method of manufacturing glycosamine from microbial biomass |
CNB02806321XA CN100350051C (en) | 2001-02-16 | 2002-02-15 | Glucosamine and method of making glucosamine from microbial biomass |
JP2002566371A JP2005507233A (en) | 2001-02-16 | 2002-02-15 | Method for producing glucosamine from glucosamine and microbial biomass |
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CA2438233A CA2438233C (en) | 2001-02-16 | 2002-02-15 | Glucosamine and method of making glucosamine from microbial biomass |
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US10/326,549 US7049433B2 (en) | 2001-02-16 | 2002-12-19 | Glucosamine and method of making glucosamine from microbial biomass |
US10/685,125 US7816514B2 (en) | 2001-02-16 | 2003-10-13 | Glucosamine and method of making glucosamine from microbial biomass |
US11/394,981 US7923437B2 (en) | 2001-02-16 | 2006-03-31 | Water soluble β-glucan, glucosamine, and N-acetylglucosamine compositions and methods for making the same |
US11/395,013 US8222232B2 (en) | 2001-02-16 | 2006-03-31 | Glucosamine and N-acetylglucosamine compositions and methods of making the same fungal biomass |
US12/613,386 US20100112035A1 (en) | 2001-02-16 | 2009-11-05 | Multiple component food product useful for delivering glucosamine and/or n-acetyl-d-glucosamine |
US12/727,176 US8034925B2 (en) | 2001-02-16 | 2010-03-18 | Glucosamine and method of making glucosamine from microbial biomass |
US13/225,160 US20110319358A1 (en) | 2001-02-16 | 2011-09-02 | Glucosamine and method of making glucosamine from microbial biomass |
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JPWO2016199934A1 (en) * | 2015-06-12 | 2018-03-29 | 大日精化工業株式会社 | Preservative composition and preservation solution for fruits and vegetables, and fruits and vegetables |
WO2017057654A1 (en) * | 2015-10-02 | 2017-04-06 | 大日精化工業株式会社 | Agent for inhibiting discoloration of plants due to physical/chemical stimulation |
CN105603024B (en) * | 2016-03-08 | 2019-12-06 | 扬州日兴生物科技股份有限公司 | Method for extracting glucosamine from corn grit by biotransformation |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2040879A (en) * | 1934-06-21 | 1936-05-19 | Du Pont | Substantially undegraded deacetylated chitin and process for producing the same |
US3232836A (en) * | 1959-08-24 | 1966-02-01 | Pfizer & Co C | Facilitating healing of body surface wounds by intravenous administration of n-acetyl glucosamine, glucosamine, or pharmaceutically acceptable acid salts of glucosamine |
US3903268A (en) * | 1968-02-12 | 1975-09-02 | Lescarden Ltd | Chitin and chitin derivatives for promoting wound healing |
US3632754A (en) * | 1968-02-12 | 1972-01-04 | Lescarden Ltd | Use of chitin for promoting wound healing |
IT1044707B (en) * | 1968-10-26 | 1980-04-21 | Rotta Research Lab | PROCEDURE FOR THE PREPARATION OF GLUCOSANINE SALTS AND PHARMACEUTICAL PREPARATIONS INCLUDING THESE GLUCOSAMINE SALTS AS ACTIVE AGENTS |
US3911116A (en) * | 1970-04-13 | 1975-10-07 | Leslie L Balassa | Process for promoting wound healing with chitin derivatives |
US3914413A (en) * | 1971-02-10 | 1975-10-21 | Leslie L Balassa | Process for facilitating wound healing with N-acetylated partially depolymerized chitin materials |
US4056432A (en) * | 1971-07-06 | 1977-11-01 | Calgon Corporation | Process for making paper products of improved dry strength |
IT1104351B (en) * | 1978-06-14 | 1985-10-21 | Muzzarelli Riccardo | THE GLUCAN COMPLEX CHITOSANO THE METHOD OF ITS PRODUCTION FROM MUSHROOMS AND YEASTS AND ITS USES |
IT1148050B (en) * | 1981-04-30 | 1986-11-26 | Rotta Research Lab | STABLE GLUCOSAMINE SULPHATE COMPOUND PROCEDURE FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING SUCH COMPOUND |
US4948881A (en) * | 1982-12-28 | 1990-08-14 | Sanofi | Process for the depolymerization and sulfation of polysaccharides |
US4886541A (en) * | 1984-10-05 | 1989-12-12 | Washington State University Research Foundation | Method for treating cereal crop seed with chitosan to enhance yield, root growth and stem strength |
US4806474A (en) * | 1985-06-10 | 1989-02-21 | Miles Inc. | Preparation of mycelial chitosan and glucan fractions from microbial biomass |
JPH0220292A (en) * | 1988-07-06 | 1990-01-23 | Agency Of Ind Science & Technol | Production of depolymerized chitosan |
JPH02135134A (en) * | 1988-11-16 | 1990-05-24 | Katokichi:Kk | Membrane for separating water-alcohol mixed liquid |
US5262310A (en) * | 1991-05-31 | 1993-11-16 | Akebono Brake Industry Co, Ltd. | Enzymatic decomposition method of chitin-containing materials |
JPH05199892A (en) * | 1991-09-11 | 1993-08-10 | Shin Etsu Chem Co Ltd | Production of chitosan |
US5219749A (en) * | 1991-10-09 | 1993-06-15 | Institute For Molecular Biology & Biotechnology/Forth | Process for isolating and preparing purified chitin deacetylase |
US5792647A (en) * | 1995-02-13 | 1998-08-11 | The Johns Hopkins University | Bacterial catabolism of chitin |
DE19680077D2 (en) * | 1995-02-13 | 1998-02-12 | Abion Ohg | Process for the preparation of chitosan-glucan complexes, masses which can be produced therefrom and their use |
JP2769992B2 (en) * | 1995-04-25 | 1998-06-25 | 工業技術院長 | Glucosamine-6-phosphate deaminase |
US5998173A (en) * | 1996-02-20 | 1999-12-07 | The University Of Bristish Columbia | Process for producing N-acetyl-D-glucosamine |
US6117851A (en) * | 1996-12-13 | 2000-09-12 | Lescarden Inc. | Treatment of osteoarthritis by administering poly-N-acetyl-D-glucosamine |
US5905035A (en) * | 1997-04-15 | 1999-05-18 | Asahi Kasei Kogyo Kabushiki Kaisha | Fungus useful for chitin production |
US5730876A (en) * | 1997-05-30 | 1998-03-24 | Hyang-Ja You | Separation and purification of low molecular weight chitosan using multi-step membrane separation process |
ES2346022T3 (en) * | 1997-12-23 | 2010-10-07 | Baxter Healthcare S.A. | PROCEDURE FOR THE EXTRACTION AND ISOLATION OF BACTERIAL CAPSULAR POLYSACARIDS FOR USE AS VACCINES OR LINKS TO PROTEINS AS VACCINES OF CONJUGATES. |
US5843923A (en) * | 1998-05-22 | 1998-12-01 | Jame Fine Chemicals, Inc. | Glucosamine sulfate potassium chloride and process of preparation thereof |
US5902801A (en) * | 1998-05-22 | 1999-05-11 | Jame Fine Chemicals, Inc. | Glucosamine sulfate metal chloride compositions and process of preparing same |
-
2001
- 2001-02-16 US US09/785,695 patent/US20020115639A1/en not_active Abandoned
-
2002
- 2002-02-15 JP JP2002566371A patent/JP2005507233A/en active Pending
- 2002-02-15 CN CNA2007101698025A patent/CN101186626A/en active Pending
- 2002-02-15 EP EP02742474A patent/EP1362119B1/en not_active Expired - Lifetime
- 2002-02-15 AT AT02742474T patent/ATE493502T1/en active
- 2002-02-15 CA CA2438233A patent/CA2438233C/en not_active Expired - Lifetime
- 2002-02-15 CN CNB02806321XA patent/CN100350051C/en not_active Expired - Lifetime
- 2002-02-15 BR BR0207287-4A patent/BR0207287A/en not_active Application Discontinuation
- 2002-02-15 DE DE60238745T patent/DE60238745D1/en not_active Expired - Lifetime
- 2002-02-15 WO PCT/US2002/004468 patent/WO2002066667A1/en active Application Filing
- 2002-12-19 US US10/326,549 patent/US7049433B2/en not_active Expired - Lifetime
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8034925B2 (en) | 2001-02-16 | 2011-10-11 | Cargill, Incorporated | Glucosamine and method of making glucosamine from microbial biomass |
US20060172392A1 (en) * | 2001-02-16 | 2006-08-03 | Cargill, Incorporated | Water soluble beta-glucan, glucosamine, and N-acetylglucosamine compositions and methods for making the same |
US20060178344A1 (en) * | 2001-02-16 | 2006-08-10 | Cargill, Incorporated | Glucosamine and N-acetylglucosamine and methods of making the same fungal biomass |
US7923437B2 (en) | 2001-02-16 | 2011-04-12 | Cargill, Incorporated | Water soluble β-glucan, glucosamine, and N-acetylglucosamine compositions and methods for making the same |
US8222232B2 (en) | 2001-02-16 | 2012-07-17 | Cargill, Incorporated | Glucosamine and N-acetylglucosamine compositions and methods of making the same fungal biomass |
US20130302412A1 (en) * | 2001-04-30 | 2013-11-14 | The Ramaekers Family Trust | Transfer Factor Compositions |
US7364880B2 (en) * | 2002-02-01 | 2008-04-29 | Cargill, Incorporated | Integration of at least two processes to re-use acid |
US20050148052A1 (en) * | 2002-02-01 | 2005-07-07 | Ray Charles D. | Integration of at least two processes to re-use acid |
US20060003965A1 (en) * | 2002-11-01 | 2006-01-05 | Fosdick Lawrence D | N-acetyl-d-glucosamine (nag) supplemented food products and beverages |
US20060058263A1 (en) * | 2002-11-01 | 2006-03-16 | Rogers Brent D | Heat pasturized liquids containing glucosamine |
US20060246114A1 (en) * | 2002-11-01 | 2006-11-02 | Rogers Brent D | Multiple component food product useful for delivering glucosamine and/or nacetyl-d-glucosamine |
CZ298944B6 (en) * | 2006-01-17 | 2008-03-19 | Výzkumný ústav potravinárský Praha, v.v.i. | Isolation method of chitin-glucan complex from fungal mycelia by autolysis and enzymatic hydrolysis |
CN109001470A (en) * | 2018-09-30 | 2018-12-14 | 南京财经大学 | A kind of precise determination method of protein content in edible mushroom |
Also Published As
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BR0207287A (en) | 2005-05-03 |
US7049433B2 (en) | 2006-05-23 |
EP1362119A1 (en) | 2003-11-19 |
JP2005507233A (en) | 2005-03-17 |
CN100350051C (en) | 2007-11-21 |
WO2002066667A1 (en) | 2002-08-29 |
DE60238745D1 (en) | 2011-02-10 |
CA2438233C (en) | 2012-05-01 |
CN1496408A (en) | 2004-05-12 |
EP1362119B1 (en) | 2010-12-29 |
WO2002066667A8 (en) | 2003-11-06 |
ATE493502T1 (en) | 2011-01-15 |
CN101186626A (en) | 2008-05-28 |
US20030148998A1 (en) | 2003-08-07 |
CA2438233A1 (en) | 2002-08-29 |
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