CN111773375A - 一种用于促进骨生长、维持骨健康的骨多肽组合物和口服液 - Google Patents
一种用于促进骨生长、维持骨健康的骨多肽组合物和口服液 Download PDFInfo
- Publication number
- CN111773375A CN111773375A CN202010661996.6A CN202010661996A CN111773375A CN 111773375 A CN111773375 A CN 111773375A CN 202010661996 A CN202010661996 A CN 202010661996A CN 111773375 A CN111773375 A CN 111773375A
- Authority
- CN
- China
- Prior art keywords
- bone
- polypeptide composition
- bone polypeptide
- oral liquid
- promoting
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 129
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 122
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 121
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 115
- 239000000203 mixture Substances 0.000 title claims abstract description 73
- 239000007788 liquid Substances 0.000 title claims abstract description 46
- 230000001737 promoting effect Effects 0.000 title claims abstract description 21
- 230000008468 bone growth Effects 0.000 title claims abstract description 15
- 230000037180 bone health Effects 0.000 title claims abstract description 12
- 230000001954 sterilising effect Effects 0.000 claims abstract description 32
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 24
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 claims abstract description 15
- 239000008267 milk Substances 0.000 claims abstract description 15
- 235000013336 milk Nutrition 0.000 claims abstract description 15
- 210000004080 milk Anatomy 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 9
- 238000000605 extraction Methods 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 235000013305 food Nutrition 0.000 claims description 10
- 239000004365 Protease Substances 0.000 claims description 9
- 239000012736 aqueous medium Substances 0.000 claims description 8
- 108091005804 Peptidases Proteins 0.000 claims description 7
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 7
- 235000019419 proteases Nutrition 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 108090000631 Trypsin Proteins 0.000 claims description 6
- 102000004142 Trypsin Human genes 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 239000012588 trypsin Substances 0.000 claims description 6
- 230000003301 hydrolyzing effect Effects 0.000 claims description 5
- 238000010298 pulverizing process Methods 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 108090000284 Pepsin A Proteins 0.000 claims description 4
- 102000057297 Pepsin A Human genes 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 4
- 229940111202 pepsin Drugs 0.000 claims description 4
- 108010009736 Protein Hydrolysates Proteins 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- 108090000317 Chymotrypsin Proteins 0.000 claims description 2
- 108090000526 Papain Proteins 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 229960002376 chymotrypsin Drugs 0.000 claims description 2
- 108010007119 flavourzyme Proteins 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 229940055729 papain Drugs 0.000 claims description 2
- 235000019834 papain Nutrition 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 229960001322 trypsin Drugs 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 210000003557 bones of lower extremity Anatomy 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 16
- 230000035876 healing Effects 0.000 abstract description 9
- 208000001132 Osteoporosis Diseases 0.000 abstract description 8
- 230000037182 bone density Effects 0.000 abstract description 8
- 238000003860 storage Methods 0.000 abstract description 4
- 241001465754 Metazoa Species 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 2
- 206010061363 Skeletal injury Diseases 0.000 abstract 1
- 238000005238 degreasing Methods 0.000 abstract 1
- 208000010392 Bone Fractures Diseases 0.000 description 15
- 241000700159 Rattus Species 0.000 description 15
- 206010017076 Fracture Diseases 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 14
- 239000000413 hydrolysate Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 10
- 239000000796 flavoring agent Substances 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 210000003414 extremity Anatomy 0.000 description 8
- 235000019634 flavors Nutrition 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000004376 Sucralose Substances 0.000 description 6
- 235000013372 meat Nutrition 0.000 description 6
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 6
- 235000019408 sucralose Nutrition 0.000 description 6
- 241000283690 Bos taurus Species 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- 210000000963 osteoblast Anatomy 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 210000000689 upper leg Anatomy 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 235000019645 odor Nutrition 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000770536 Bacillus thermophilus Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- YRQNKMKHABXEJZ-UVQQGXFZSA-N chembl176323 Chemical compound C1C[C@]2(C)[C@@]3(C)CC(N=C4C[C@]5(C)CCC6[C@]7(C)CC[C@@H]([C@]7(CC[C@]6(C)[C@@]5(C)CC4=N4)C)CCCCCCCC)=C4C[C@]3(C)CCC2[C@]2(C)CC[C@H](CCCCCCCC)[C@]21C YRQNKMKHABXEJZ-UVQQGXFZSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 206010043827 tibia fracture Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
-
- 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
- A23L3/00—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs
- A23L3/34—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals
- A23L3/3454—Preservation of foods or foodstuffs, in general, e.g. pasteurising, sterilising, specially adapted for foods or foodstuffs by treatment with chemicals in the form of liquids or solids
- A23L3/3463—Organic compounds; Microorganisms; Enzymes
- A23L3/3526—Organic compounds containing nitrogen
-
- 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
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- 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
- A23L33/17—Amino acids, peptides or proteins
- A23L33/19—Dairy proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Zoology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及骨多肽制品技术领域,具体公开一种用于促进骨生长、维持骨健康的骨多肽组合物以及其制备的口服液。所述骨多肽组合物由动物四肢骨经提取、脱脂、酶解过滤和灭菌等工序制得,质量高,口味好,具有促进骨生长、提高骨密度、促进骨伤愈合、改善骨质疏松等功效。由所述骨多肽组合物和牛奶碱性蛋白制成的骨多肽口服液,促进骨生长和保持骨健康的功效得到了进一步的提高,并且具有良好的贮存稳定性。
Description
技术领域
本发明涉及骨多肽制品技术领域,具体涉及一种用于促进骨生长、维持骨健康的骨多肽组合物和口服液。
背景技术
骨多肽是从动物骨中提取得到的一种多肽组合物,其通过促进成骨细胞增殖和破骨细胞凋亡且对骨代谢和血液相关指标具有积极作用,可用于促进骨折愈合、治疗骨质疏松症和消炎镇痛等,临床应用广泛。研究表明,对胫骨骨折患者,给予骨多肽治疗,有着良好的疗效,能够有效促进患者的足踝功能恢复,改善骨性生长因子,有利于促进患者骨折愈合;对四肢骨折患者给予复方骨多肽注射液治疗,可有效缩短愈合时间,促进患者骨折愈合,具有非常高的临床应用价值。
骨多肽制剂多为注射剂,使用较为不便,基于骨多肽的保健功效,目前有报道开始研究骨多肽的口服剂型。
动物骨中富含丰富的营养物质,因此在提取骨多肽的过程中容易被细菌等污染,所以为了长期保存,需要进行灭菌处理。作为灭菌处理方法,由于成本低且简便,加热灭菌是最常采用的处理方法。但是,提取液中一般含有芽胞菌等耐热性高的微生物,例如嗜热芽胞杆菌属等,提取液被这些微生物污染的可能性很高,为了防止这种现象,灭菌处理时需要长时间的消毒处理,但提取液中存在多肽、氨基酸、还原糖、脂质、芳香族化合物等风味前体物质,并且这此物质之间会发生反应(如美德反应),在长时间灭菌过程中,会生成新的风味物质和加热气味,如呋喃、噻唑、吡咯、吡啶、苦味氨基酸、甜味氨基酸、咸味氨基酸、苦味肽、甜味肽、鲜味肽等,从而改变了骨多肽组合物的风味。在加热杀菌处理中,为了避免产生新的风味物质和加热气味而缩短加热时间的情况下,杀菌不足,很有可能受到芽胞菌的污染。特别是芽胞菌中,如果芽胞的耐热性高,加热处理不充分,则孢子残留的可能性很高。
液体制剂中,为了有效地杀菌,除了加热的方法,还采用添加防腐剂、加压等方法。添加剂如溶菌酶、苯甲酸及其钠盐、ε-聚赖氨酸盐酸盐、山梨酸及其钾盐等,虽然可以起到一定的抑菌作用,但仍需要进行一定程度的加热处理,添加剂和骨多肽组合物相互作用会产生新的风味物质和加热气味,导致骨多肽产品本身的风味降低。如果采用加热加压的方法,骨多肽组合物中的有效成分会聚合或分解,骨多肽组合物的功效也会降低。
发明内容
针对以上技术现状,本发明提供一种用于促进骨生长、维持骨健康的骨多肽组合物及其应用,并提供由该骨多肽组合物制成的口服液。
为达到上述发明目的,本发明采用了如下的技术方案:
一种用于促进骨生长、维持骨健康的骨多肽组合物,采用以下方法制备得到:取哺乳动物四肢骨,粉碎后加水性介质提取,分离脂肪后得提取液,所述提取液中加入蛋白酶进行水解,水解完毕后过滤得水解液,水解液经灭菌得所述骨多肽组合物溶液;所述灭菌的条件为124-126℃下灭菌20-50 s,或129-131℃下灭菌10-15s。
作为本发明的一种实施方案,所述水性介质为水、无机盐水溶液、亲水性有机溶剂或水与亲水性有机溶剂的混合液;所述无机盐为氯化钠、氯化钾、氯化钙或碳酸钠,其水溶液的浓度为0.8-1.0%;所述亲水性有机溶剂为乙醇,混合液中水的体积含量为10-90%;所述水性介质的用量为所述哺乳动物四肢骨质量的2-15倍。
作为本发明的一种实施方案,所述水性介质的pH为6-10,所述提取的温度为120-140℃,提取时间3-20 h。
作为本发明的一种实施方案,所述分离脂肪的温度为40-90℃,在该温度下脂肪融解成液体,利于脂肪与提取液不互溶的特点,可在该温度下从上部取走脂肪或从设备下部放出提取液从而实现二者的分离。
作为本发明的一种实施方案,所述蛋白酶为胃蛋白酶、胰蛋白酶、糜蛋白酶、木瓜蛋白酶或风味蛋白酶,其用量为所述提取液质量的0.01-10%,酶解温度20-80℃,酶解时间0.5-40 h。
本发明采用特定方法制备得到的骨多肽组合物溶液,有害微生物可被完全杀灭,并且能够保持骨多肽本身的风味,没有异味,骨多肽组合物中分子量10 kDa以下的小分子肽含量95%以上,该骨多肽组合物用于制备促进骨生长及维持骨健康的食品、保健食品或药品,具有显著的功效。
本发明还提供一种骨多肽口服液,包括上述骨多肽组合物以及牛奶碱性蛋白,且二者的质量比为1:0.04-1。所述的骨多肽组合物的质量以氮含量计,下同。
将上述骨多肽组合物制成口服液,服用方便,满足人们日常作为食品、保健品或药品服用的需求。骨多肽组合物中含有大量的小分子肽,这些小分子肽在保存过程中容易聚合成大分子,从而使其功效降低。本发明通过在骨多肽口服液中加入牛奶碱性蛋白,可以显著抑制小分子肽的聚合,从而延长口服液的保质期。骨多肽组合物口服后在消化液的作用下容易降低活性,这也是目前骨多肽制剂多为注射剂的原因,而本发明发现,加入牛奶碱性蛋白在保持口服液稳定性的同时还能改善骨多肽组合物的口服效果,提高生物利用度。此外,牛奶碱性蛋白本身也具有促进骨骼生长、预防骨质疏松的作用,在日本等国家已被广泛加入保健食品等中广泛应用,将其加入本发明骨多肽组合物中,没有任何副作用,并且还能够提高口服液促进骨生长、维持骨健康的功效。
作为本发明的一种实施方案,所述骨多肽口服液中骨多肽组合物的质量浓度为5-200 g/L。在此浓度下,骨多肽口服液具有更优的贮存稳定性和功效。
作为本发明的一种实施方案,所述骨多肽口服液中还包括食品工业和/或药品制剂中允许的辅料,如营养强化剂、抗氧化剂、增稠剂、酸度调节剂、甜味剂、防腐剂、香精等。具体工艺中,可将牛奶碱性蛋白和辅料加入四肢骨的蛋白酶水解液中,然后再经灭菌制得。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。
实施例1
(1)取刚解冻的猪四肢骨100 kg,其外观色泽鲜明,无臭味或异味,取骨上残留肉检测挥发性盐基氮0.06 g/kg,将所述猪四肢骨用水洗净,剔肉。
(2)将上述猪四肢骨粉碎成粒径2 mm以下的颗粒,投入加压釜,加入400 kg水,加热到140℃提取3小时。
(3)等提取液温度降至80℃,从加压釜底部排出提取液,进行脂肪分离,得到四肢骨提取液390 kg。
(4)四肢骨提取液加入其质量1%的胰蛋白酶,40℃水解1小时。
(5)板框过滤得水解液360 kg,125℃下灭菌20 s,即得骨多肽组合物溶液。
实施例2
(1)取新鲜的牛四肢骨100 kg,其外观色泽鲜明,无臭味或异味,取骨上残留肉检测挥发性盐基氮0.08 g/kg,将所述牛四肢骨用水洗净,剔肉。
(2)将上述牛四肢骨粉碎成粒径2 mm以下的颗粒,投入加压釜,加入200kg 10%(v/v)乙醇水溶液,加热到120℃提取10小时。
(3)等提取液温度降至40℃,从加压釜底部排出提取液,进行脂肪分离,得到四肢骨提取液230 kg。
(4)四肢骨提取液加入其质量5 %的胃蛋白酶,30℃水解2小时。
(5)板框过滤得水解液210 kg,130℃下灭菌10 s,即得骨多肽组合物溶液。
实施例3
(1)取新鲜的猪四肢骨100 kg,其外观色泽鲜明,无臭味或异味,取骨上残留肉检测挥发性盐基氮0.05 g/kg,将所述猪四肢骨用水洗净,剔肉。
(2)将上述猪四肢骨粉碎成粒径 2mm以下的颗粒,投入加压釜,加入1000kg 氯化钠水溶液(质量浓度为0.9%),加热到130℃提取5小时。
(3)等提取液温度降至90℃,从加压釜底部排出提取液,进行脂肪分离,得到四肢骨提取液850 kg。
(4)四肢骨提取液加入其质量0.2 %的胃蛋白酶,30℃水解10小时。
(5)板框过滤得水解液790 kg,125℃下灭菌50 s,即得骨多肽组合物溶液。
对比例1
实施例1获得的水解液在125℃下灭菌10 s,得骨多肽组合物溶液。
对比例2
实施例1获得的水解液在130℃下灭菌20 s,得骨多肽组合物溶液。
对比例3
实施例1获得的水解液在135℃下灭菌10 s,得骨多肽组合物溶液。
试验例1
将实施例1-3以及对比例1-3得到的骨多肽组合物溶液在37℃和55℃的环境下进行一周的孵化。孵化后,从各个骨多肽组合物溶液中无菌抽取1ml样品,将各个样品倒入培养皿中,再注入琼脂培养基20~30 ml。将含有骨多肽组合物的琼脂培养基分别在37℃和55℃下进行孵化24小时。孵化后,观察各个培养基上有没有出现菌斑。
另将实施例1-3以及对比例1-3得到的骨多肽组合物溶液由16人进行口味的官能试验。评价是以完全没有变味的情况为1分,以有变味的的情况为7分的7等级评价法进行评价,取16人评分的平均值,平均值1以上不满2的情况下,设为“无”;平均值2以上不满3的情况下,设为“小”;平均值3以上不满4的情况下,设为“有点”;平均值4以上不满6的情况下,设为“有”;平均值在6以上不满7的情况下,设为“大”。
试验结果如表1所示。
表1 微生物检测及感官评价结果
样品 | 微生物检测(37℃) | 嗜热菌检测(55℃) | 口味 |
实施例1 | - | - | 小 |
实施例2 | - | - | 无 |
实施例3 | - | - | 小 |
对比例1 | - | + | 无 |
对比例2 | - | - | 有 |
对比例3 | - | - | 有 |
注:“+”代表有菌斑,“-”代表无菌斑。
可见,实施例1-3的骨多肽组合物溶液中微生物均被完全杀灭,且口味无变化或变化很小,而对比例1-3或不能杀灭耐热微生物,或口味发生明显改变,产品质量不尽理想。
试验例2
将实施例1-3的骨多肽组合物溶液用于成骨细胞增殖试验,具体过程如下:
取出生24h以内的健康Wistar大鼠颅盖骨,用PBS清洗,去除结缔组织,剪碎至1mm3大小,加入0.25%的胰蛋白酶消化10 min,弃酶液,加入0.1%的Ⅱ型胶原酶和0.25的胰蛋白酶消化4-5次,每次15 min,合并消化液,加入含胎牛血清的DMEM培养基终止消化。500 r/min离心10 min,沉淀即为成骨细胞,将其加入含15%FBS的DMEM培养基中重悬,以每毫升105个细胞接种于培养瓶中,于37℃、饱和湿度、CO2分压5%的细胞培养箱中进行培养。待细胞长满培养瓶底后,吸出培养基,用0.25%的胰蛋白酶消化,进行传代培养。将传至第3代的细胞以每孔5×103个细胞的密度接种于96孔培养液中,每孔加入含15%FBS的培养基200μl,在37℃、5%CO2及饱和湿度条件下培养。24 h细胞完全贴壁吸去培养基,用实施例1-3的骨多肽组合物溶液进行培养,三蒸水作为空白对照,于第3天用MTT法分析培养液的吸光值,从而计算成骨戏班的增值率,结果如表2所示。
表2 成骨细胞增殖试验结果
组别 | OD值 |
空白对照 | 0.122±0.015 |
实施例1 | 0.376±0.021 |
实施例2 | 0.407±0.028 |
实施例3 | 0.393±0.017 |
可见,本发明的骨多肽组合物对成骨细胞增殖有显著的促进作用,口服该骨多肽组合物具有促进骨骼生长的功效。
实施例4
在实施例1的猪四肢骨水解液中加水稀释至骨多肽组合物含量为10 g/L,加入牛奶碱性蛋白,使其含量为0.4 g/L,再加入常规量的三氯蔗糖,按照实施例1的灭菌条件进行灭菌,得骨多肽口服液。
实施例5
在实施例2的牛四肢骨水解液中加水稀释至骨多肽组合物含量为5 g/L,加入牛奶碱性蛋白,使其含量为5 g/L,再加入常规量的三氯蔗糖,按照实施例2的灭菌条件进行灭菌,得骨多肽口服液。
实施例6
将实施例3的猪四肢骨水解液浓缩至骨多肽组合物含量为200 g/L,加入牛奶碱性蛋白,使其含量为10 g/L,再加入常规量的三氯蔗糖,按照实施例3的灭菌条件进行灭菌,得骨多肽口服液。
试验例3
取出生4周的断乳大鼠,常规饲养的同时每日按0.5 ml/kg体重灌胃实施例1-3的骨多肽组合物溶液和实施例4-6的骨多肽口服液,实验3周后解剖大鼠,剥离左侧股骨,测量大鼠股骨中点骨密度以及骨钙含量。等量纯净水灌胃作为空白对照。试验结果如表3所示。
表3 骨密度及骨钙含量试验结果
可见,实施例1-3的骨多肽组合物溶液能显著提高骨密度和骨钙含量,对于维持骨骼健康具有积极的效果。而实施例4-6的骨多肽口服液中骨多肽组合物浓度低于实施例1-3,然而其效果却明显优于骨多肽组合物,可见牛奶碱性蛋白的加入显著提高了口服液的效果,推测可能是牛奶碱性蛋白能够减少消化液对骨多肽活性的影响,从而提高了其生物利用度。这为本发明的骨多肽组合物用于制备具有相应功能的食品、保健食品或口服药品提供了基础。
试验例4
取体重为250-300 g的雄性SD大鼠,麻醉后经股外侧切口暴露股骨,线锯离断其股骨中段,1mm克氏钉固定,得到骨折模型。将模型大鼠随机分为7组,每组20只,分别每日按照1ml/kg体重灌胃实施例1-3的骨多肽组合物溶液、实施例4-6的骨多肽口服液以及纯净水,30天后通过X光片评价各组大鼠的骨折愈合情况,记录各组的X线评分。具体的X线评分标准如下:0分:骨折线清晰无变化;1分:骨折线出现模糊;2分:骨折线模糊且出现明显的连接迹象;3分:骨折线完全消失,骨痂出现;4分:骨折线消失且骨髓腔密度减低;5分:骨折线消失且骨髓腔完全再通。各组大鼠的评分结果如表4所示。
表4 SD大鼠骨折愈合X线评分结果
组别 | 评分 |
对照(纯净水) | 1.9±0.3 |
实施例1 | 3.3±0.3 |
实施例2 | 3.1±0.5 |
实施例3 | 3.5±0.7 |
实施例4 | 4.4±0.5 |
实施例5 | 4.5±0.5 |
实施例6 | 4.7±0.4 |
可见,本发明的骨多肽组合物和骨多肽口服液均对骨折愈合有促进作用,骨多肽口服液的效果骨多肽组合物组也有显著的差别。
试验例5
取10月龄SD大鼠,经背部切口切除双侧卵巢以制作骨质疏松模型,造模成功的大鼠分为7组,每组20只,分别每日按照1 ml/kg体重灌胃实施例1-3的骨多肽组合物溶液、实施例4-6的骨多肽口服液以及纯净水,常规喂养3个月后,处死大鼠,取左侧股骨和胫骨,测定其骨密度,结果如表5所示。
表5 各组骨质疏松模型的骨密度对比
组别 | 股骨密度(g/cm<sup>2</sup>) | 胫骨密度(g/cm<sup>2</sup>) |
对照(纯净水) | 0.208±0.009 | 0.203±0.005 |
实施例1 | 0.223±0.006 | 0.216±0.008 |
实施例2 | 0.220±0.011 | 0.215±0.006 |
实施例3 | 0.228±0.012 | 0.218±0.009 |
实施例4 | 0.257±0.008 | 0.228±0.012 |
实施例5 | 0.255±0.013 | 0.226±0.008 |
实施例6 | 0.259±0.010 | 0.231±0.011 |
可见,本发明的骨多肽组合物和骨多肽口服液能够明显提高骨质疏松大鼠的骨密度,本发明产品可口服用于改善骨质疏松。
由以上试验例可见,本发明的骨多肽组合物和骨多肽口服液口服后具有显著的促进骨生长、提高骨密度、促进骨伤愈合、改善骨质疏松等功效,且实验动物在试验期间及试验后均未出现不良反应,证明本发明产品口服安全有效,为其成为具有相应功效的食品、保健食品和药品提供了基础。
对比例4
在实施例4的猪四肢骨水解液中加水稀释至骨多肽组合物含量为10 g/L,再加入与实施例4等量的三氯蔗糖,按照实施例4的灭菌条件进行灭菌,得骨多肽口服液。
对比例5
在实施例5的牛四肢骨水解液中加水稀释至骨多肽组合物含量为5g/L,再加入与实施例5等量的三氯蔗糖,按照实施例5的灭菌条件进行灭菌,得骨多肽口服液。
对比例6
将实施例6的猪四肢骨水解液浓缩至骨多肽组合物含量为200g/L,再加入与实施例6等量的三氯蔗糖,按照实施例6的灭菌条件进行灭菌,得骨多肽口服液。
试验例6
将实施例4-6及对比例4-6的骨多肽口服液在常温下自然放置24个月,检测其中相对分子质量10kDa以下的多肽含量。另取实施例4-6和对比例4-6的骨多肽口服液样品于50℃下放置10天,检测其中相对分子质量10kDa以下的多肽含量。以结果如表6所示。
表6 稳定性试验结果
可见,加入牛奶碱性蛋白能够减少骨多肽口服液中小分子肽的聚合,提高口服液的稳定性。这为本发明产品的长期有效性提供了基础。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换或改进等,均应包含在本发明的保护范围之内。
Claims (8)
1.一种用于促进骨生长、维持骨健康的骨多肽组合物,其特征在于,采用以下方法制备得到:取哺乳动物四肢骨,粉碎后加水性介质提取,分离脂肪后得提取液,所述提取液中加入蛋白酶进行水解,水解完毕后过滤得水解液,水解液经灭菌得所述骨多肽组合物溶液;所述灭菌的条件为124-126 ℃下灭菌20-50 s,或129-131 ℃下灭菌10-15 s。
2.如权利要求1所述的骨多肽组合物,其特征在于,所述水性介质为水、无机盐水溶液、亲水性有机溶剂或水与亲水性有机溶剂的混合液;所述无机盐为氯化钠、氯化钾、氯化钙或碳酸钠,其水溶液的质量浓度为0.8-1.0%;所述亲水性有机溶剂为乙醇,混合液中水的体积含量为10-90%;所述水性介质的用量为所述哺乳动物四肢骨质量的2-15倍。
3.如权利要求1所述的骨多肽组合物,其特征在于,所述水性介质的pH为6-10,所述提取的温度为120-140 ℃,提取时间3-20 h。
4.如权利要求1所述的骨多肽组合物,其特征在于,所述分离脂肪的温度为40-90 ℃。
5.如权利要求1所述的骨多肽组合物,其特征在于,所述蛋白酶为胃蛋白酶、胰蛋白酶、糜蛋白酶、木瓜蛋白酶或风味蛋白酶,其用量为所述提取液质量的0.01-10%,酶解温度20-80 ℃,酶解时间0.5-40 h。
6.一种用于促进骨生长、维持骨健康的骨多肽口服液,其特征在于,包括权利要求1-5任一项所述的骨多肽组合物和牛奶碱性蛋白,二者的质量比为1:0.04-1。
7.如权利要求6所述的骨多肽口服液,其特征在于,其中所述骨多肽组合物的质量浓度为5-200 g/L。
8.如权利要求6所述的骨多肽口服液,其特征在于,还包括食品工业和/或药品制剂中允许的辅料。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010661996.6A CN111773375B (zh) | 2020-07-10 | 2020-07-10 | 一种用于促进骨生长、维持骨健康的骨多肽组合物和口服液 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010661996.6A CN111773375B (zh) | 2020-07-10 | 2020-07-10 | 一种用于促进骨生长、维持骨健康的骨多肽组合物和口服液 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111773375A true CN111773375A (zh) | 2020-10-16 |
CN111773375B CN111773375B (zh) | 2023-09-12 |
Family
ID=72767176
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010661996.6A Active CN111773375B (zh) | 2020-07-10 | 2020-07-10 | 一种用于促进骨生长、维持骨健康的骨多肽组合物和口服液 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111773375B (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5932259A (en) * | 1994-09-30 | 1999-08-03 | Kato; Ken | Bone reinforcing agent and foods and drinks product containing the same |
CN102232600A (zh) * | 2011-08-17 | 2011-11-09 | 山东朝能福瑞达生物科技有限公司 | 利用芽孢激活和蛋白稳定制备中性燕麦浓浆的方法 |
CN103039976A (zh) * | 2012-12-05 | 2013-04-17 | 无锡市天赐康生物科技有限公司 | 一种增加骨密度的保健食品及其制备方法 |
CN103783254A (zh) * | 2013-07-02 | 2014-05-14 | 吴长海 | 一种牦牛骨胶原蛋白肽的制备方法 |
CN107177658A (zh) * | 2017-07-28 | 2017-09-19 | 美泰科技(青岛)股份有限公司 | 一种软骨胶原蛋白肽的制备方法 |
-
2020
- 2020-07-10 CN CN202010661996.6A patent/CN111773375B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5932259A (en) * | 1994-09-30 | 1999-08-03 | Kato; Ken | Bone reinforcing agent and foods and drinks product containing the same |
CN102232600A (zh) * | 2011-08-17 | 2011-11-09 | 山东朝能福瑞达生物科技有限公司 | 利用芽孢激活和蛋白稳定制备中性燕麦浓浆的方法 |
CN103039976A (zh) * | 2012-12-05 | 2013-04-17 | 无锡市天赐康生物科技有限公司 | 一种增加骨密度的保健食品及其制备方法 |
CN103783254A (zh) * | 2013-07-02 | 2014-05-14 | 吴长海 | 一种牦牛骨胶原蛋白肽的制备方法 |
CN107177658A (zh) * | 2017-07-28 | 2017-09-19 | 美泰科技(青岛)股份有限公司 | 一种软骨胶原蛋白肽的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN111773375B (zh) | 2023-09-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5276813B2 (ja) | エラスチン分解ペプチド並びにエラスチン及びその酵素分解ペプチドの製造方法 | |
JP4592127B2 (ja) | 骨吸収抑制剤 | |
KR20100014572A (ko) | 오스테오칼신 함유 추출물의 제조방법 | |
US20210128640A1 (en) | Hyaluronic acid production promoting agent | |
US6649590B2 (en) | Method of producing fractions containing a high concentration of milk basic cystatin and decomposition products thereof | |
US10881621B2 (en) | Sintered ferrous amino acid particles and use of the same against a virus | |
JP4647750B2 (ja) | 乳塩基性シスタチン高含有画分及びその分解物の製造法 | |
AU784087B2 (en) | Method of producing fractions containing a high concentration of milk basic cystatin and decomposition products thereof | |
US11975041B2 (en) | Composition comprising CHP (cyclo-his pro) for preventing, improving or treating of bone loss related disease | |
CN111773375B (zh) | 一种用于促进骨生长、维持骨健康的骨多肽组合物和口服液 | |
JP4053686B2 (ja) | 生理活性健康食品 | |
KR20220130966A (ko) | 녹용 발효추출물을 포함하는 골다공증 또는 여성 갱년기 운동성 감소의 예방 또는 치료용 조성물 | |
JPWO2009057282A1 (ja) | 骨吸収抑制用食品素材 | |
JP6786490B2 (ja) | 抗肥満用組成物 | |
JP6117963B2 (ja) | ポリアミンを有効成分とする、組織の再生を促進するための組成物 | |
JP2021097626A (ja) | 低分子コラーゲンペプチド組成物及びその製造方法 | |
JP2019041696A (ja) | 経口用組成物 | |
JP5909173B2 (ja) | ポリアミンを有効成分とする、組織の再生を促進するための組成物 | |
JP2005343852A (ja) | 骨靭性向上用素材 | |
TWI804459B (zh) | 乳過氧化酶、胱抑素、hmg樣蛋白質及/或它們之分解物之用途 | |
CN113768159B (zh) | 软骨机能改善用组合物 | |
JP6279851B2 (ja) | 筋萎縮防止及び/又は筋合成促進剤 | |
CN111778305A (zh) | 一种用于提高免疫力的脾多肽组合物及口服液 | |
CN118086433A (zh) | 鳕鱼皮活性多肽粉及其用于抗病毒、杀菌的用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |