JPH11286452A - Agent for protecting infection of pathogenic bacterium and virus - Google Patents
Agent for protecting infection of pathogenic bacterium and virusInfo
- Publication number
- JPH11286452A JPH11286452A JP10103959A JP10395998A JPH11286452A JP H11286452 A JPH11286452 A JP H11286452A JP 10103959 A JP10103959 A JP 10103959A JP 10395998 A JP10395998 A JP 10395998A JP H11286452 A JPH11286452 A JP H11286452A
- Authority
- JP
- Japan
- Prior art keywords
- iron
- lactoferrin
- infection
- binding
- pathogenic bacteria
- 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
- 244000052616 bacterial pathogen Species 0.000 title claims abstract description 43
- 208000015181 infectious disease Diseases 0.000 title claims abstract description 42
- 241000700605 Viruses Species 0.000 title claims abstract description 34
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 138
- 108010063045 Lactoferrin Proteins 0.000 claims abstract description 89
- 102000010445 Lactoferrin Human genes 0.000 claims abstract description 89
- 229910052742 iron Inorganic materials 0.000 claims abstract description 71
- 235000013305 food Nutrition 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 11
- 239000003223 protective agent Substances 0.000 claims abstract description 9
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 claims description 59
- 235000021242 lactoferrin Nutrition 0.000 claims description 58
- 229940078795 lactoferrin Drugs 0.000 claims description 58
- 230000009993 protective function Effects 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims 1
- 241000712461 unidentified influenza virus Species 0.000 abstract description 15
- 241000701022 Cytomegalovirus Species 0.000 abstract description 8
- 241000194019 Streptococcus mutans Species 0.000 abstract description 4
- 241000588722 Escherichia Species 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 34
- 230000000694 effects Effects 0.000 description 23
- 238000000034 method Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- 230000001717 pathogenic effect Effects 0.000 description 12
- 241000588724 Escherichia coli Species 0.000 description 11
- 229960005486 vaccine Drugs 0.000 description 11
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000004793 Polystyrene Substances 0.000 description 5
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 5
- 229920002223 polystyrene Polymers 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- 239000000427 antigen Substances 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 239000003443 antiviral agent Substances 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- -1 iron ions Chemical class 0.000 description 4
- 235000013336 milk Nutrition 0.000 description 4
- 239000008267 milk Substances 0.000 description 4
- 210000004080 milk Anatomy 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- 230000009385 viral infection Effects 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 230000008260 defense mechanism Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 206010022000 influenza Diseases 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 208000009889 Herpes Simplex Diseases 0.000 description 2
- 208000000903 Herpes simplex encephalitis Diseases 0.000 description 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 239000005862 Whey Substances 0.000 description 2
- 102000007544 Whey Proteins Human genes 0.000 description 2
- 108010046377 Whey Proteins Proteins 0.000 description 2
- 230000004520 agglutination Effects 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 208000002925 dental caries Diseases 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000035931 haemagglutination Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 108010028463 kappa-casein glycomacropeptide Proteins 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 235000020183 skimmed milk Nutrition 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 2
- 229960002555 zidovudine Drugs 0.000 description 2
- PJVXUVWGSCCGHT-ZPYZYFCMSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;(3s,4r,5r)-1,3,4,5,6-pentahydroxyhexan-2-one Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)C(=O)CO PJVXUVWGSCCGHT-ZPYZYFCMSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010016952 Food poisoning Diseases 0.000 description 1
- 208000019331 Foodborne disease Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241001542907 Influenza B virus (B/Singapore/222/79) Species 0.000 description 1
- 241001500351 Influenzavirus A Species 0.000 description 1
- 102000008133 Iron-Binding Proteins Human genes 0.000 description 1
- 108010035210 Iron-Binding Proteins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 230000000356 anti-lactoferrin effect Effects 0.000 description 1
- 230000002882 anti-plaque Effects 0.000 description 1
- 108010038047 apolactoferrin Proteins 0.000 description 1
- 235000015197 apple juice Nutrition 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000004075 cariostatic agent Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 231100000153 central nervous system (CNS) toxicity Toxicity 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 235000013353 coffee beverage Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 229940099472 immunoglobulin a Drugs 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940031551 inactivated vaccine Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000018773 low birth weight Diseases 0.000 description 1
- 231100000533 low birth weight Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000008476 powdered milk Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960003636 vidarabine Drugs 0.000 description 1
- 230000007501 viral attachment Effects 0.000 description 1
- 235000021246 κ-casein Nutrition 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
【0001】[0001]
【発明の属する技術分野】本発明は、新規な病原性細菌
及びウイルスに対する感染防御剤に関する。また、本発
明は、病原性細菌及びウイルスに対する感染防御機能を
賦与した新規な医薬及び飲食品に関する。TECHNICAL FIELD The present invention relates to a novel agent for preventing infection against pathogenic bacteria and viruses. In addition, the present invention relates to a novel medicine, food and drink which has a function of protecting against infection with pathogenic bacteria and viruses.
【0002】[0002]
【従来の技術】一般に、病原性細菌の生体への感染は、
標的細胞すなわち生体上皮の細胞表層に存在する複合糖
質の糖鎖構造(レセプター)を認識して結合することに
よりなるといわれている。そして、この病原性細菌の生
体への感染に対する一般的な治療法として、抗生物質の
使用がある。この抗生物質は、増殖した病原性細菌を死
滅させることにより、感染による病気を治療するという
もので、病原性細菌の感染過程の最終段階で行われるも
のである。このように、抗生物質による病原性細菌感染
症の治療は、発病後の生体に対する治療法として非常に
有効であるが、抗生物質の性格上、様々な副作用やアレ
ルギー症状を引き起こす等の問題も多い。2. Description of the Related Art In general, infection of living organisms by pathogenic bacteria is
It is said to be formed by recognizing and binding to the sugar chain structure (receptor) of the complex carbohydrate present on the target cell, ie, the cell surface of living epithelium. As a general treatment for infection of living organisms by the pathogenic bacteria, there is use of antibiotics. This antibiotic is used at the final stage of the infection process of pathogenic bacteria, by treating the disease caused by the infection by killing the grown pathogenic bacteria. Thus, treatment of pathogenic bacterial infections with antibiotics is very effective as a treatment for living organisms after the onset of disease, but due to the nature of antibiotics, there are many problems such as causing various side effects and allergic symptoms. .
【0003】一般に、生体は、病原性細菌による感染に
対し、その感染初期の段階においての防御機構を備えて
いる。例えば、消化管における分泌型免疫グロブリンA
を主とする免疫グロブリンによる防御機構がそれであ
り、これらの免疫グロブリンは、病原性細菌の標的細胞
への付着を阻止することにより、病原性細菌による感染
から生体を守っている。In general, living organisms have a defense mechanism against infection by pathogenic bacteria at an early stage of infection. For example, secretory immunoglobulin A in the digestive tract
These immunoglobulins are mainly defense mechanisms, and these immunoglobulins protect living bodies from infection by pathogenic bacteria by preventing the attachment of pathogenic bacteria to target cells.
【0004】ところで、一般に、レセプターやレセプタ
ーと類似した構造をもつ物質は、病原性細菌の細胞表層
のレセプター結合部位に特異的に結合し、病原性細菌の
標的細胞への結合を特異的に阻害することが期待されて
いる。この特異的な作用は、病原性細菌の感染を初期の
段階で阻止するという意味で、前述した免疫グロブリン
による防御機構に類似しているといえる。すなわち、こ
のような病原性細菌のレセプター結合部位に特異的に結
合する物質は、病原性細菌の感染を未然に防ぐことがで
き、しかも、作用が穏やかで副作用が少ない病原性細菌
感染防御剤となり得る。In general, a receptor or a substance having a structure similar to a receptor specifically binds to a receptor binding site on the cell surface of a pathogenic bacterium and specifically inhibits the binding of the pathogenic bacterium to a target cell. Is expected to. This specific action can be said to be similar to the above-mentioned immunoglobulin defense mechanism in that infection of pathogenic bacteria is prevented at an early stage. In other words, a substance that specifically binds to the receptor binding site of such a pathogenic bacterium can prevent infection of the pathogenic bacterium, and has a mild action and has fewer side effects as a protective agent for the pathogenic bacterium infection. obtain.
【0005】一方、ウイルス感染症については、現在ま
でに抗ウイルス剤に関する多くの研究がなされている。
しかし、ウイルスは、宿主細胞の増殖機能に依存して増
殖するという性質を有するため、薬剤によってウイルス
感染症を治療することは極めて困難である。例えば、ウ
イルスの細胞への侵入を阻害するアマンタジンは、イン
フルエンザウイルスAに効果があるといわれているが、
治療効果が弱い上に中枢神経毒性等の副作用も出現し、
臨床薬としては殆ど利用されていない現状にある。現
在、わが国で使用が認可されている抗ウイルス剤として
は、ウイルス遺伝子の合成を阻害するアシクロビル(単
純ヘルペスや単純ヘルペス脳炎等に適用)、ビダラビン
(単純ヘルペスや単純ヘルペス脳炎等に適用)、点眼剤
用のイドクスウリジン(ヘルペス角膜炎に適用)、アジ
ドチミジン(AIDSに適用)等が知られているが、ア
ジドチミジンは、全身投与によりしばしば重篤な副作用
が出現し、治療薬としては未だ問題を抱えている。[0005] On the other hand, with regard to viral infectious diseases, many studies on antiviral agents have been made so far.
However, it is extremely difficult to treat viral infectious diseases with drugs, because viruses have the property of growing depending on the growth function of host cells. For example, amantadine, which inhibits virus entry into cells, is said to be effective against influenza virus A,
The therapeutic effect is weak and side effects such as central nervous system toxicity also appear,
At present, it is hardly used as a clinical drug. Currently, antiviral agents approved for use in Japan include acyclovir, which inhibits the synthesis of viral genes (applied to herpes simplex and herpes simplex encephalitis, etc.), vidarabine (applied to herpes simplex and herpes simplex encephalitis, etc.), eye drops There are known idoxuridine (applied to herpes keratitis), azidothymidine (applied to AIDS) and the like, but azidothymidine often causes serious side effects by systemic administration, and it still has a problem as a therapeutic drug. I have.
【0006】また、抗ウイルス剤として、近年、注目を
集めているインターフェロンが知られている。このイン
ターフェロンは、ウイルスの細胞内増殖を抑制する因子
であり、遺伝子組み換えの技術を利用して生産されてい
るが、高価であり、副作用も問題となっている。[0006] As an antiviral agent, interferon, which has recently attracted attention, is known. This interferon is a factor that suppresses the intracellular growth of the virus, and is produced using a genetic recombination technique, but is expensive and has side effects.
【0007】これらの現状から、ウイルス性疾患に対す
る対策として、ウイルスによる感染を予防するワクチン
の投与が最も普及している。このワクチンには、ウイル
スを何らかの方法で弱毒化した生ワクチンやウイルスを
ホルマリン等で処理して作成した不活性化ワクチン、ウ
イルスの抗原部分のみを精製したコンポーネントワクチ
ンがある。そして、これらのワクチンにより、大部分の
ウイルス性疾患を予防することが可能となっている。し
かし、最も代表的なウイルス性疾患の一つであるインフ
ルエンザでは、ワクチンによる感染予防は困難である。
なぜなら、インフルエンザの場合、インフルエンザウイ
ルスのエンベロープに存在する抗原をワクチンとして使
用しているが、この抗原部分がしばしば変異を繰り返
し、元のウイルスに対するワクチンは変異型のウイルス
に対して何ら効果を示さないからである。また、HIV
のようにワクチンとして利用可能な抗原が不明な場合や
臓器移植後の免疫抑制剤投与による免疫機能低下時にし
ばしば発症するサイトメガロウイルス感染症等に対して
は、ワクチンによる感染予防は困難である。さらに、ワ
クチンによっては、病気に罹患する危険があり、ワクチ
ンの接種による副作用も考慮すべき問題である。[0007] Under these circumstances, as a measure against viral diseases, the administration of vaccines for preventing infection by viruses is most widespread. The vaccine includes a live vaccine in which the virus is attenuated by some method, an inactivated vaccine prepared by treating the virus with formalin or the like, and a component vaccine in which only the antigen portion of the virus is purified. These vaccines have made it possible to prevent most viral diseases. However, influenza, one of the most typical viral diseases, is difficult to prevent by vaccine.
Because, in the case of influenza, an antigen present in the envelope of the influenza virus is used as a vaccine, and this antigen portion is frequently mutated, and a vaccine against the original virus has no effect on the mutated virus Because. Also, HIV
As described above, it is difficult to prevent infection with a vaccine for cytomegalovirus infection, which frequently occurs when an antigen usable as a vaccine is unknown, or when the immune function decreases due to administration of an immunosuppressant after organ transplantation. Furthermore, some vaccines are at risk of illness, and the side effects of vaccination must be considered.
【0008】近年、ウイルス学の研究進展により、ウイ
ルスのヒトへの感染についても、前述した病原性細菌に
よる感染の場合と同様、標的細胞すなわち生体上皮の表
層に存在する複合糖質の糖鎖構造等からなるレセプター
にウイルスが結合して細胞内へウイルスが侵入すること
が明らかになっている。例えば、HIVは、Tリンパ球
の表面に存在するCD4レセプターに結合して感染する
ので、CD4を大量に血中に投与することによりAID
Sの発症を予防することができるといわれている。ま
た、インフルエンザウイルスも、細胞の表面に存在する
シアル酸結合複合糖質分子からなるレセプターに結合し
て感染するので、このシアル酸結合複合糖質分子や類似
の糖鎖構造を有する物質を投与することにより、インフ
ルエンザウイルスによる感染を予防したり、感染後の他
の細胞や組織へのインフルエンザウイルスの伝搬を防御
することが考えられている。[0008] In recent years, due to the progress of research in virology, virus infection to humans has been promoted in the same manner as in the case of infection by pathogenic bacteria described above, and the sugar chain structure of complex carbohydrates present on the surface layer of target cells, ie, living epithelium It has been clarified that a virus binds to a receptor composed of the above, and the virus enters the cell. For example, HIV binds to and infects the CD4 receptor present on the surface of T lymphocytes, so that administration of a large amount of CD4 into the blood leads to AID.
It is said that the onset of S can be prevented. Also, influenza virus is infected by binding to a receptor composed of sialic acid-linked glycoconjugate molecules present on the surface of cells, and therefore, administering this sialic acid-linked glycoconjugate molecule or a substance having a similar sugar chain structure. Thus, it is considered to prevent infection by the influenza virus or to prevent the spread of the influenza virus to other cells or tissues after the infection.
【0009】従来、病原性細菌やウイルスのレセプター
への結合を阻害して感染を防御する効果を有する物質と
して、κカゼインやそのプロテアーゼ分解物であるκカ
ゼイングリコマクロペプチドが知られている (特開昭 6
3-284133号公報) 。また、同様のメカニズムでκカゼイ
ングリコマクロペプチドが抗歯垢及び抗齲歯剤として有
効であることも知られている (特開昭 63-233911号公
報) 。さらに山川らは、インフルエンザウイルスによる
赤血球凝集を阻害する物質をヒト血球から単離して、こ
の物質がシアル酸を構成糖とする糖タンパク質であるこ
とを明らかにした(生化学, vol.31, pp.416-421, 195
9) 。Heretofore, kappa casein and kappa casein glycomacropeptide which is a protease degradation product thereof have been known as substances having an effect of preventing the infection by inhibiting the binding of pathogenic bacteria or viruses to the receptor (particularly). Kaisho 6
3-284133). It is also known that κ casein glycomacropeptide is effective as an anti-plaque and anti-caries agent by the same mechanism (Japanese Patent Application Laid-Open No. 63-233911). Furthermore, Yamakawa et al. Isolated a substance that inhibits hemagglutination caused by influenza virus from human blood cells and revealed that this substance is a glycoprotein composed of sialic acid (Biochemistry, vol. 31, pp. .416-421, 195
9).
【0010】ところで、乳中に含まれる感染防御機能を
有するタンパク質として、ラクトフェリンが知られてい
る。このラクトフェリンの病原性細菌に対する感染防御
機能は、ラクトフェリンのもつ鉄キレート力により、そ
の増殖に必要な鉄が病原性細菌から奪い取られて増殖が
抑制されることによる。しかしながら、このラクトフェ
リンによる病原性細菌増殖抑制効果は一時的なものであ
り、また、他の食品と同時にラクトフェリンを摂取する
場合には、ラクトフェリンが食品中に含まれる全ての鉄
分をキレートするので、多量のラクトフェリンを摂取す
る必要があるという問題がある。[0010] Lactoferrin is known as a protein having a protective function against infection contained in milk. The protective function of lactoferrin against pathogenic bacteria is based on the fact that lactoferrin has its iron-chelating ability to remove the iron necessary for its growth from pathogenic bacteria and suppress its growth. However, the effect of lactoferrin on suppressing the growth of pathogenic bacteria is temporary, and when lactoferrin is ingested simultaneously with other foods, lactoferrin chelate all iron contained in the foods, so that large amounts of lactoferrin are chelated. There is a problem that it is necessary to take lactoferrin.
【0011】なお、ラクトフェリンに関しては、その鉄
キレート力による病原性細菌増殖抑制機能とは全く別の
メカニズムによる病原性細菌の腸管細胞への付着を阻止
する感染防御機能が示唆されているが、この病原性細菌
感染防御機能における鉄結合型ラクトフェリンの役割に
ついては、全く明らかにされていない。また、分子中の
糖鎖構造がウイルスの細胞への付着を阻止するので、抗
ウイルス剤としてもラクトフェリンは有効であることが
知られている(特開平2-233619号公報)。しかし、この
ウイルス感染防御機能においても、鉄結合型ラクトフェ
リンの役割は全く明らかにされていない。[0011] Lactoferrin has a function of preventing infection of intestinal cells by preventing pathogenic bacteria from adhering to intestinal cells by a mechanism completely different from the function of inhibiting the growth of pathogenic bacteria by its iron chelating ability. The role of iron-binding lactoferrin in the protective function against pathogenic bacterial infection has not been clarified at all. In addition, it is known that lactoferrin is also effective as an antiviral agent because the sugar chain structure in the molecule prevents virus attachment to cells (Japanese Patent Application Laid-Open No. 2-233619). However, the role of iron-binding lactoferrin in this protective function against virus infection has not been clarified at all.
【0012】[0012]
【発明が解決しようとする課題】本発明者らは、従来よ
り、ラクトフェリンのもつ薬理作用に注目し、鋭意研究
を進めていたところ、病原性細菌やウイルスの細胞への
付着を阻止する機能に関しては、鉄非結合型ラクトフェ
リンに殆ど活性がないのに対し、鉄結合型ラクトフェリ
ンに強い活性があることを見出した。そして、この活性
は、鉄結合型ラクトフェリンの鉄飽和度に依存すること
を見出し、本発明を完成するに至った。したがって、本
発明は、病原性細菌及びウイルスに対する新規な感染防
御剤あるいはこのような感染防御機能を賦与した新規な
医薬品及び飲食品を提供することにある。さらに、具体
的には本発明は、鉄結合型ラクトフェリンを有効成分と
する病原性細菌及びウイルス感染防御剤を提供すること
を課題とする。また、本発明は、鉄結合型ラクトフェリ
ンを配合して病原性細菌及びウイルス感染防御機能を賦
与した医薬品及び飲食品を提供することを課題とする。DISCLOSURE OF THE INVENTION The present inventors have been paying attention to the pharmacological action of lactoferrin and have been intensively studying it. As a result, regarding the function of blocking the adhesion of pathogenic bacteria and viruses to cells. Found that iron-bound lactoferrin had little activity, whereas iron-bound lactoferrin had strong activity. Then, they found that this activity depends on the iron saturation of iron-binding lactoferrin, and completed the present invention. Therefore, an object of the present invention is to provide a novel infection protective agent against pathogenic bacteria and viruses, or a novel pharmaceutical product and food or drink provided with such an infection protective function. Furthermore, specifically, an object of the present invention is to provide a pathogenic bacterium and a virus infection protective agent containing iron-binding lactoferrin as an active ingredient. Another object of the present invention is to provide a pharmaceutical product and a food or drink which are provided with a protective function against pathogenic bacteria and viruses by blending iron-binding lactoferrin.
【0013】[0013]
【課題を解決するための手段】本発明は、病原性細菌や
ウイルスに対する感染防御剤の有効成分として、あるい
は病原性細菌やウイルスに対する感染防御機能を医薬及
び飲食品に賦与するために、鉄結合型ラクトフェリンを
使用することを特徴とする。DISCLOSURE OF THE INVENTION The present invention relates to an iron-binding agent which is used as an active ingredient of an agent for preventing infection against pathogenic bacteria and viruses, or for imparting a function of protecting infection against pathogenic bacteria and viruses to medicines and foods and drinks. It is characterized by using type lactoferrin.
【0014】本発明で使用する鉄結合型ラクトフェリン
は、ウシ等の哺乳動物の乳、あるいは、これらの脱脂乳
やホエー等を原料としてイオン交換クロマトグラフィー
等の処理を施すことにより得られるラクトフェリンに、
例えば、塩化第二鉄を溶解したクエン酸ナトリウム等の
溶液中で鉄イオンをキレートさせた後、透析して脱塩す
ることにより調製することができる。また、ラクトフェ
リンに鉄イオンをキレートさせる際には、遺伝子組み換
えの技術により得られたラクトフェリンを使用しても良
いし、市販のラクトフェリンを使用しても良い。The iron-bound lactoferrin used in the present invention is obtained by subjecting lactoferrin obtained by subjecting milk of mammals such as cattle or the like to skim milk, whey or the like to a material such as ion-exchange chromatography, and the like.
For example, it can be prepared by chelating iron ions in a solution of sodium citrate or the like in which ferric chloride is dissolved, and then dialyzing and desalting. When chelating iron ions to lactoferrin, lactoferrin obtained by a genetic recombination technique may be used, or commercially available lactoferrin may be used.
【0015】ウシ等の哺乳動物の乳、あるいは、これら
の脱脂乳やホエー等から、ラクトフェリンを得る方法と
しては、モノクローナル抗ラクトフェリン抗体を使用す
る方法 (特開昭 60-166619号公報、特開昭 60-145200号
公報) 、ヘパリンを固定化した架橋型のセルロースやキ
トサンを担体として使用する方法 (特開昭 63-255299号
公報) 、架橋型ポリサッカライドの硫酸エステル化物を
担体として使用する方法 (特開昭 63-255300号公報) 、
スルホン基を導入した多糖類アフィニティ担体を使用す
る方法 (特開平3-109400号公報) 、陽イオン交換体を担
体として使用し、イオン強度及びpHを調整することによ
り溶出する方法 (特開平5-202098号公報) 等が知られて
いる。本発明で使用する鉄結合型ラクトフェリンの鉄飽
和度としては、好ましくは20%以上であり、より好まし
くは50%以上 100%までである。As a method for obtaining lactoferrin from milk of mammals such as cows or skim milk or whey thereof, a method using a monoclonal anti-lactoferrin antibody (JP-A-60-166619, JP-A-60-166619) No. 60-145200), a method using heparin-immobilized crosslinked cellulose or chitosan as a carrier (Japanese Patent Laid-Open No. 63-255299), a method using a sulfated ester of a crosslinked polysaccharide as a carrier ( JP-A-63-255300),
A method using a polysaccharide affinity carrier into which a sulfone group is introduced (JP-A-3-109400), a method using a cation exchanger as a carrier, and eluting by adjusting the ionic strength and pH (Japanese Patent Laid-Open No. 5-109400). 202098) and the like. The iron-saturated lactoferrin used in the present invention has an iron saturation of preferably 20% or more, more preferably 50% or more and 100% or more.
【0016】[0016]
【発明の実施の形態】本発明の病原性細菌及びウイルス
感染防御剤は、鉄結合型ラクトフェリンを有効成分とし
たものである。病原性細菌及びウイルス感染防御剤の剤
型は、錠剤、カプセル剤、顆粒剤、散剤、粉剤等とする
ことが望ましい。これらは経口的に投与することが望ま
しい。また、これらの剤型は、従来知られている普通の
方法で製造することができる。例えば製剤製造上許容さ
れる担体、賦形剤等と混合して成型する。また、本発明
の病原性細菌及びウイルス感染防御機能を賦与した医薬
及び飲食品は、鉄結合型ラクトフェリンを前記のような
剤型として医薬、特に経口剤に配合したり、鉄結合型ラ
クトフェリンを牛乳、乳飲料、コーヒー飲料、ジュー
ス、ゼリー、ビスケット、パン、麺、ソーセージ等の飲
食品、さらには、各種粉乳の他、乳児、幼児及び低出生
体重児等を対象とする栄養組成物に配合したりしたもの
である。これらは、病原性細菌及びウイルスに対する感
染防御機能を有するので、これらの病原性細菌あるいは
ウイルスに感染する疾病を予防し、あるいは疾病を治療
する用途に用いられる。このような疾病には、大腸菌に
基づく下痢、食中毒、ストレプトコッカス ミュータン
スに基づく齲蝕病、インフルエンザウイルスに基づくイ
ンフルエンザ、サイトメガロウイルスに基づく妊婦等へ
の感染が例示される。BEST MODE FOR CARRYING OUT THE INVENTION The protective agent for pathogenic bacteria and viruses of the present invention contains iron-binding lactoferrin as an active ingredient. The dosage form of the agent for preventing pathogenic bacteria and virus infection is desirably tablets, capsules, granules, powders, powders and the like. These are desirably administered orally. In addition, these dosage forms can be produced by a conventionally known ordinary method. For example, the mixture is molded with a carrier, excipient, or the like which is acceptable for the production of the preparation. In addition, the medicines and foods and drinks imparted with the protective function against pathogenic bacteria and viruses of the present invention may be prepared by mixing iron-binding lactoferrin in pharmaceuticals, particularly oral preparations, as described above, or mixing iron-binding lactoferrin with milk. , Milk beverages, coffee beverages, juices, jellies, biscuits, breads, noodles, sausages and other foods and beverages, as well as various types of powdered milk, as well as nutritional compositions for infants, infants, low birth weight infants, etc. Or something. Since they have a function of protecting infection against pathogenic bacteria and viruses, they are used for preventing diseases infected with these pathogenic bacteria or viruses or for treating diseases. Examples of such diseases include diarrhea based on Escherichia coli, food poisoning, dental caries based on Streptococcus mutans, influenza based on influenza virus, and infection of pregnant women based on cytomegalovirus.
【0017】本発明で、病原性細菌及びウイルスに対す
る感染防御効果を発揮させるためには、成人の場合、鉄
結合型ラクトフェリンを1日当たり 0.1〜 5,000mg摂取
できるように配合量等を調整すれば良い。In the present invention, in order to exert the effect of protecting against infection with pathogenic bacteria and viruses, the amount of iron-binding lactoferrin may be adjusted so that 0.1 to 5,000 mg per day can be taken for adults. .
【0018】次に、実施例及び試験例を示し、本発明を
詳しく説明する。Next, the present invention will be described in detail with reference to examples and test examples.
【実施例1】鉄結合型ラクトフェリン (鉄飽和度 100
%) の調製 市販のラクトフェリン (オレオフィナ社製) 5gの1%水
溶液に1/5量の0.003M塩化鉄(III) を含む0.1Mクエン
酸三ナトリウム溶液を加えて1時間撹拌し、鉄飽和度 1
00%の鉄結合型ラクトフェリン溶液を調製した。この溶
液に含まれるラクトフェリンについては、全てのラクト
フェリン分子に鉄イオンが結合して鉄飽和度が 100%に
なっていることを確認した。次に、この鉄結合型ラクト
フェリン溶液を透析チューブに封入し、蒸留水に対して
透析して余分な塩類を除去した後、凍結乾燥して、鉄飽
和度 100%の鉄結合型ラクトフェリン粉末5gを得た。Example 1 Iron-bound lactoferrin (iron saturation 100
%) To a 5% 1% aqueous solution of lactoferrin (manufactured by Oleofina Co.) was added 1/5 of a 0.1 M trisodium citrate solution containing 0.003 M iron (III) chloride, and the mixture was stirred for 1 hour. 1
A 00% iron-bound lactoferrin solution was prepared. Regarding lactoferrin contained in this solution, it was confirmed that iron ions were bound to all lactoferrin molecules and the iron saturation was 100%. Next, the iron-bound lactoferrin solution was sealed in a dialysis tube, dialyzed against distilled water to remove excess salts, and lyophilized to obtain 5 g of iron-bound lactoferrin powder having a 100% iron saturation. Obtained.
【0019】鉄非結合型ラクトフェリン (鉄飽和度0
%、アポラクトフェリン) の調製 市販のラクトフェリン (オレオフィナ社製) 5gの1%水
溶液を透析チューブに封入し、20倍量の0.05%EDTA
を含む0.1Mクエン酸水溶液に対して4℃で30時間透析し
た。引き続き、この透析チューブを取り出して、蒸留水
に対して24時間透析し、鉄飽和度0%の鉄非結合型ラク
トフェリン(アポラクトフェリン)溶液を調製した。こ
の溶液に含まれるラクトフェリンについては、全てのラ
クトフェリン分子に鉄イオンが結合しておらず鉄飽和度
が0%になっていることを確認した。次に、透析を完了
した溶液を凍結乾燥して、鉄飽和度0%の鉄非結合型ラ
クトフェリン粉末5gを得た。 Iron-free lactoferrin (iron saturation 0
%, Apolactoferin ) A commercially available lactoferrin (manufactured by Oleofina) 5 g of a 1% aqueous solution was sealed in a dialysis tube, and a 20-fold volume of 0.05% EDTA was prepared.
Was dialyzed at 4 ° C. for 30 hours against a 0.1 M aqueous citric acid solution containing. Subsequently, the dialysis tube was taken out and dialyzed against distilled water for 24 hours to prepare a non-iron-bound lactoferrin (apolactoferrin) solution having an iron saturation of 0%. Regarding lactoferrin contained in this solution, it was confirmed that iron ions were not bound to all lactoferrin molecules and the iron saturation was 0%. Next, the dialyzed solution was freeze-dried to obtain 5 g of iron-free lactoferrin powder having an iron saturation of 0%.
【0020】鉄結合型ラクトフェリン (鉄飽和度20%及
び鉄飽和度50%) の調製 得られた鉄結合型ラクトフェリン (鉄飽和度 100%) 粉
末を水に溶解し、濃度が 10mg/mlの鉄結合型ラクトフェ
リン (鉄飽和度 100%) 水溶液を調製すると共に、得ら
れた鉄非結合型ラクトフェリン (鉄飽和度0%) 粉末を
水に溶解し、濃度が 10mg/mlの鉄非結合型ラクトフェリ
ン (鉄飽和度0%) 水溶液を調製した。そして、この鉄
結合型ラクトフェリン (鉄飽和度 100%) 水溶液と鉄非
結合型ラクトフェリン (鉄飽和度0%) 水溶液を2:8
の割合で混合することにより、鉄飽和度20%の鉄結合型
ラクトフェリン溶液を調製し、凍結乾燥して、鉄飽和度
20%の鉄結合型ラクトフェリン粉末を得た。 Iron-bound lactoferrin (iron saturation 20%
The iron-binding lactoferrin (iron saturation 100%) powder obtained preparation of fine iron saturation 50%) was dissolved in water, concentration prepare 10mg / ml of iron-binding lactoferrin (iron saturation 100%) aqueous solution At the same time, the obtained powder of iron-free lactoferrin (iron saturation 0%) was dissolved in water to prepare an aqueous solution of iron-free lactoferrin (iron saturation 0%) having a concentration of 10 mg / ml. Then, the aqueous solution of iron-binding lactoferrin (iron saturation 100%) and the aqueous solution of non-iron-binding lactoferrin (iron saturation 0%) are mixed in a ratio of 2: 8.
A lactoferrin solution having an iron saturation of 20% is prepared by mixing at a ratio of
A 20% iron-bound lactoferrin powder was obtained.
【0021】また、この鉄結合型ラクトフェリン (鉄飽
和度 100%) 水溶液と鉄非結合型ラクトフェリン (鉄飽
和度0%) 水溶液を5:5の割合で混合することによ
り、鉄飽和度50%の鉄結合型ラクトフェリン溶液を調製
し、凍結乾燥して、鉄飽和度50%の鉄結合型ラクトフェ
リン粉末を得た。The aqueous solution of iron-binding lactoferrin (iron saturation 100%) and the aqueous solution of non-iron-binding lactoferrin (iron saturation 0%) are mixed at a ratio of 5: 5 to give an iron saturation of 50%. An iron-binding lactoferrin solution was prepared and freeze-dried to obtain an iron-binding lactoferrin powder having an iron saturation of 50%.
【0022】[0022]
【試験例1】実施例1に示した方法で調製した各鉄飽和
度の鉄結合型ラクトフェリン及び鉄非結合型ラクトフェ
リンを試料として、病原性大腸菌に対する感染防御効果
を調べた。感染防御試験は、次のように行った。ヒト小
腸細胞(JTC-17)(東京医科大より分譲を受けた)を 2
5cm2底面積培養フラスコで、5%牛胎児血清を含むダル
ベッコ変法イーグル培地(5%FCS/DMEM)によ
り、37℃、二酸化炭素濃度5%で培養した。細胞がほぼ
コンフルエントの状態に増殖したら、常法に従ってトリ
プシン−EDTAで細胞を剥がし取り、遠心操作により
細胞を集めた。上清を吸い出し、新たに5%FCS/D
MEM 8mlに細胞を懸濁した。得られた細胞懸濁液各1
mlを10ml容ポリスチレンチューブ(ファルコン社2095)
に入れ、37℃で3日間培養した。Test Example 1 Using the iron-binding lactoferrin and the non-iron-binding lactoferrin of each iron saturation prepared by the method shown in Example 1, the effect of protecting against infection with pathogenic Escherichia coli was examined. The infection protection test was performed as follows. Human small intestinal cells (JTC-17) (available from Tokyo Medical University)
The cells were cultured in a 5 cm 2 bottom area culture flask in Dulbecco's modified Eagle's medium (5% FCS / DMEM) containing 5% fetal calf serum at 37 ° C. and a carbon dioxide concentration of 5%. When the cells had grown to a nearly confluent state, the cells were peeled off using trypsin-EDTA according to a conventional method, and the cells were collected by centrifugation. Aspirate the supernatant and add 5% FCS / D
The cells were suspended in 8 ml of MEM. Each of the obtained cell suspensions 1
ml 10 ml polystyrene tube (Falcon 2095)
And cultured at 37 ° C. for 3 days.
【0023】病原性大腸菌H10407株、Pb176 株(都立衛
生研より分譲を受けた)をそれぞれ1白金耳取り、普通
ブイヨン培地4mlで、37℃で1夜培養した。そして、培
養終了後、3,000rpm、10分間遠心分離することにより集
菌し、これをpH8に調整したPBSで3回洗浄した。そ
の後、病原性大腸菌をpH8に調整したPBS 1mlに懸濁
し、FITC(フルオレッセン イソチオシアネート
Fluorescein Isothiocyanate) 1mg を加えてよく溶解
し、4℃で3時間ゆっくり撹拌しながら反応させて病原
性大腸菌をFITCラベルした。ラベルした病原性大腸
菌は、PBSにて3回洗浄した後、PBS 3mlに懸濁し
た。このようにして調製したFITCラベル化病原性大
腸菌懸濁液 400μl に、各試料のPBS溶液 200μl を
混合し、37℃で1時間インキュベートした。One platinum loop of each of the pathogenic Escherichia coli strains H10407 and Pb176 (obtained from Tokyo Metropolitan Institute of Health) was cultured overnight at 37 ° C. in 4 ml of normal broth medium. After completion of the culture, the cells were collected by centrifugation at 3,000 rpm for 10 minutes and washed three times with PBS adjusted to pH 8. Thereafter, the pathogenic E. coli was suspended in 1 ml of PBS adjusted to pH 8, and FITC (fluorescein isothiocyanate) was suspended.
Fluorescein Isothiocyanate (1 mg) was added, dissolved well, and allowed to react at 4 ° C. for 3 hours with gentle stirring to label the pathogenic E. coli with FITC. The labeled pathogenic E. coli was washed three times with PBS and then suspended in 3 ml of PBS. 200 μl of a PBS solution of each sample was mixed with 400 μl of the suspension of FITC-labeled pathogenic E. coli thus prepared, and incubated at 37 ° C. for 1 hour.
【0024】一方、3日間の培養を終えたJTC-17細胞を
1,000rpmで5分間遠心分離して上清の培地を除き、さら
にPBSで3回洗浄し、これに上述の病原性大腸菌と各
試料とを混合してインキュベートした溶液 600μl を加
え、37℃で30分間インキュベートした。インキュベート
終了後、750rpmで5分間遠心分離し、細胞だけを沈澱さ
せ、細胞に付着せずに上清に残った病原性大腸菌を吸い
出した。さらに、PBSにて細胞を2回洗浄した。PB
Sで洗浄した細胞に 200U トリプシン/PBS900μl
を加えて激しく撹拌した。これに 0.1%SDS 100μl
、1mlの脱イオン水を加えて激しく撹拌し、30分静置
することにより細胞を溶解した。この溶液を蛍光分光光
度計(日立フルオレッセンススペクトロメーターF-300
0)にて励起波長 520nm、蛍光波長 520nmで相対蛍光強
度を測定し、蛍光ラベルした病原性大腸菌のJTC-17細胞
への付着を評価した。表1には試料を添加しない時の相
対蛍光強度(ブランク)を付着率 100%、蛍光ラベルし
た病原性大腸菌のポリスチレンチューブへの非特異的な
吸着(ポリスチレンチューブ内に検体と同じ条件で測定
した相対蛍光強度)を付着率0%とし、各試料を添加し
た際の付着率(%)を示している。実験は3連で行っ
た。On the other hand, after culturing for 3 days,
The medium of the supernatant was removed by centrifugation at 1,000 rpm for 5 minutes, and further washed three times with PBS. 600 μl of a solution obtained by mixing and incubating the above-mentioned pathogenic Escherichia coli and each sample was added thereto. Incubated for minutes. After the incubation, the cells were centrifuged at 750 rpm for 5 minutes to precipitate only the cells, and the pathogenic E. coli remaining in the supernatant without adhering to the cells was sucked out. Further, the cells were washed twice with PBS. PB
Add 200 U trypsin / PBS 900 μl to cells washed with S
Was added and stirred vigorously. 100% 0.1% SDS
The cells were lysed by adding 1 ml of deionized water, stirring vigorously and allowing to stand for 30 minutes. This solution is used for fluorescence spectrophotometer (Hitachi Fluorescence Spectrometer F-300)
At 0), the relative fluorescence intensity was measured at an excitation wavelength of 520 nm and a fluorescence wavelength of 520 nm, and the attachment of the fluorescently labeled pathogenic E. coli to JTC-17 cells was evaluated. Table 1 shows the relative fluorescence intensity (blank) when no sample was added, non-specific adsorption of pathogenic Escherichia coli labeled with fluorescence onto a polystyrene tube with an adhesion rate of 100% (measured under the same conditions as the sample in the polystyrene tube). (Relative fluorescence intensity) is defined as an adhesion rate of 0%, and the adhesion rate (%) when each sample was added is shown. The experiment was performed in triplicate.
【0025】[0025]
【表1】 [Table 1]
【0026】[0026]
【試験例2】実施例1に示した方法で調製した各鉄飽和
度の鉄結合型ラクトフェリン及び鉄非結合型ラクトフェ
リンを試料として、ストレプトコッカス・ミュータンス
に対する感染防御効果を調べた。試験は、次のように行
った。3種のストレプトコッカス ミュータンス(ATCC-
27670, ATCC-25175, ATCC-27351)を1白金耳取り、ブレ
インハートフージョン(BHI)培地4mlで一夜培養し
た。一夜後、3,000rpmで10分間遠心することにより集菌
し、上清の培地を吸い出した。さらに、これをPBSで
3回洗浄し、これをOD650=0.8 となるようにPBSに懸
濁した。この菌懸濁液と試料溶液を当量混合し、10mlの
ポリスチレンチューブ(ファルコン社2095)に入れ、よ
く撹拌し、37℃で3時間インキュベートした。インキュ
ベート終了後、OD650 を測定し、次式から付着率(%)
を求めた。 付着率(%)=0.4 − (X/0.4)× 100× (試料のOD65
0) 実験は2連で行い、その結果を表2に示した。これによ
ると、鉄非結合型ラクトフェリンに比べ鉄結合型ラクト
フェリンは、う歯原菌のポリスチレンチューブへの付着
を阻止し、鉄飽和度が大きい程その阻止効果は高くなる
傾向を示した。Test Example 2 Using the iron-bound lactoferrin and the non-iron-bound lactoferrin of each iron saturation prepared by the method shown in Example 1, samples were used to examine the effect of preventing infection with Streptococcus mutans. The test was performed as follows. Three types of Streptococcus mutans (ATCC-
27670, ATCC-25175, ATCC-27351) were picked from a platinum loop and cultured overnight in 4 ml of brain heart fusion (BHI) medium. After one night, the cells were collected by centrifugation at 3,000 rpm for 10 minutes, and the supernatant medium was sucked out. Further, this was washed three times with PBS, and this was suspended in PBS so that OD650 = 0.8. Equivalent amounts of the bacterial suspension and the sample solution were mixed, placed in a 10 ml polystyrene tube (Falcon 2095), mixed well, and incubated at 37 ° C for 3 hours. After the incubation, measure the OD650 and determine the adhesion rate (%) according to the following equation.
I asked. Adhesion rate (%) = 0.4-(X / 0.4) x 100 x (OD65 of sample
0) The experiment was performed in duplicate, and the results are shown in Table 2. According to this, compared with non-iron-binding lactoferrin, iron-binding lactoferrin tended to prevent adhesion of dental caries to polystyrene tubes, and the higher the iron saturation, the higher the inhibitory effect.
【0027】[0027]
【表2】 [Table 2]
【0028】[0028]
【試験例3】実施例1に示した方法で調製した各鉄飽和
度の鉄結合型ラクトフェリン及び鉄非結合型ラクトフェ
リンを試料として、インフルエンザウイルスに対する感
染防御効果を調べた。試験は、次のように行った。イン
フルエンザウイルスのヒヨコ安定化赤血球(武田薬品工
業製)及びヒト赤血球(O型)に対する凝集反応阻止
(HI)活性を測定した。HI活性は、前述した山川ら
の方法(生化学, vol.31, pp.416-421, 1959) に準じて
測定した。インフルエンザウイルスとしては、デンカ生
研より入手した不活化インフルエンザウイルスのA/山
形/120/86(H1N1)、A/新潟/102/8
1(H3N2)、A/四川/α/87(H3N2)、A
/福岡/C29/85(H2N2)、B/長崎/1/8
7、B/シンガポール/222/79、及び静岡薬科大
学より入手した不活化されていないインフルエンザウイ
ルスのA/PR/8/34(H1N1)を用いた。ヒヨ
コ安定化赤血球に対するHI活性を表3に、ヒト赤血球
に対するHI活性を表4にそれぞれ示す。これによる
と、鉄非結合型ラクトフェリンに比べ鉄結合型ラクトフ
ェリンは、インフルエンザウイルスに対して強いHI活
性を示し、鉄飽和度が大きい程その阻止効果は高くなる
傾向を示した。Test Example 3 Using an iron-binding lactoferrin and an iron-non-binding lactoferrin of each iron saturation prepared by the method shown in Example 1, the effect of protecting against influenza virus was examined. The test was performed as follows. Agglutination inhibition (HI) activity of influenza virus on chick-stabilized erythrocytes (manufactured by Takeda Pharmaceutical Co., Ltd.) and human erythrocytes (type O) was measured. The HI activity was measured according to the above-mentioned method of Yamakawa et al. (Biochemistry, vol. 31, pp. 416-421, 1959). As influenza viruses, A / Yamagata / 120/86 (H1N1) and A / Niigata / 102/8 of inactivated influenza viruses obtained from Denka Seikaken
1 (H3N2), A / Sichuan / α / 87 (H3N2), A
/ Fukuoka / C29 / 85 (H2N2), B / Nagasaki / 1/8
7, B / Singapore / 222/79, and A / PR / 8/34 (H1N1) of inactivated influenza virus obtained from Shizuoka Pharmaceutical University. Table 3 shows HI activity on chick-stabilized erythrocytes, and Table 4 shows HI activity on human erythrocytes. According to this, iron-bound lactoferrin showed stronger HI activity against influenza virus than iron-free lactoferrin, and the higher the iron saturation, the higher its inhibitory effect.
【0029】[0029]
【表3】 ────────────────────────────────── 鉄飽和度(%) ───────────────────────── 0 20 50 100 ────────────────────────────────── 山形 N.D. N.D. N.D. N.D. 新潟 4 0.13 6.25×102 1.6×102 四川 8 0.13 6.25×102 1.6×102 福岡 4 0.25 6.25×102 3.1×102 長崎 − 0.5 0.13 6.25×102 シンガポール − 0.5 0.13 6.25×102 PR − 8 1 0.25 ──────────────────────────────────[Table 3] 鉄 Iron saturation (%) ────── ─────────────────── 0 20 50 100 ─────────────────────────── ─────── Yamagata NDNDNDND Niigata 4 0.13 6.25 × 10 2 1.6 × 10 2 Sichuan 8 0.13 6.25 × 10 2 1.6 × 10 2 Fukuoka 4 0.25 6.25 × 10 2 3.1 × 10 2 Nagasaki − 0.5 0.13 6.25 × 10 2 Singapore − 0.5 0.13 6.25 × 10 2 PR − 8 1 0.25 ──────────────────────────────────
【0030】[0030]
【表4】 ────────────────────────────────── 鉄飽和度(%) ───────────────────────── 0 20 50 100 ────────────────────────────────── 山形 4 0.25 0.13 6.25×102 新潟 4 0.13 6.25×102 1.6×102 四川 8 0.13 6.25×102 1.6×102 福岡 4 0.13 6.25×102 3.1×102 長崎 − 0.5 0.13 6.25×102 シンガポール − 0.5 0.13 6.25×102 PR − 8 2 0.5 ──────────────────────────────────[Table 4] 度 Iron saturation (%) ────── ─────────────────── 0 20 50 100 ─────────────────────────── ─────── Yamagata 4 0.25 0.13 6.25 × 10 2 Niigata 4 0.13 6.25 × 10 2 1.6 × 10 2 Sichuan 8 0.13 6.25 × 10 2 1.6 × 10 2 Fukuoka 4 0.13 6.25 × 10 2 3.1 × 10 2 Nagasaki − 0.5 0.13 6.25 × 10 2 Singapore − 0.5 0.13 6.25 × 10 2 PR − 8 2 0.5 ─────────────────────────────── ───
【0031】[0031]
【試験例4】実施例1に示した方法で調製した各鉄飽和
度の鉄結合型ラクトフェリン及び鉄非結合型ラクトフェ
リンを試料として、静岡薬科大学より入手した不活化さ
れていないインフルエンザウイルスのA/PR/8/3
4(H1N1)及びA/愛知/2/68(H3N2)を
段階的に希釈し、5個のニワトリ10日卵に 0.1mlずつ尿
液喰内腔内に接種し、3日後、個々の卵の尿液50μl を
取り、これを 0.5%ヒヨコ安定化赤血球と混合、撹拌
し、赤血球の凝集によって感染率を決定した。 100%の
感染率を示した希釈倍率のウイルス希釈液の 0.1mlにそ
れぞれの鉄飽和度に調整した鉄結合型ラクトフェリン又
は鉄非結合型ラクトフェリンをそれぞれ 0.5mg溶解し、
室温で30分間インキュベートした後、ニワトリ10日卵に
0.1mlずつ尿液腔内に接種した。3日後、個々の卵の尿
液50μl を取り、赤血球凝集反応により感染率を決定し
た。1群5個の卵を使用し、各群の感染率(%)を得
た。その結果を表5に示す。これによると、鉄非結合型
ラクトフェリンに比べ鉄結合型ラクトフェリンは、イン
フルエンザウイルスに対して強い感染防御効果を示し
た。Test Example 4 Using the iron-bound lactoferrin and iron-free lactoferrin of each iron saturation prepared by the method shown in Example 1 as samples, the A / of inactivated influenza virus obtained from Shizuoka Pharmaceutical University was used. PR / 8/3
4 (H1N1) and A / Aichi / 2/68 (H3N2) were serially diluted, and inoculated into 0.1 ml of 5 chicken 10-day eggs in the space of the urine juice. 50 μl of urine fluid was taken, mixed with 0.5% chick-stabilized erythrocytes, stirred, and the infection rate was determined by agglutination of erythrocytes. Dissolve 0.5 mg each of iron-bound lactoferrin or iron-free lactoferrin adjusted to the respective iron saturation in 0.1 ml of the virus dilution at a dilution ratio showing 100% infection rate,
After incubating at room temperature for 30 minutes, add 10 days
0.1 ml was inoculated into the urine cavity. Three days later, 50 μl of the urine fluid of each egg was taken and the infection rate was determined by hemagglutination. Using five eggs per group, the infection rate (%) of each group was obtained. Table 5 shows the results. According to this, iron-bound lactoferrin showed a stronger protective effect against influenza virus than iron-free lactoferrin.
【0032】[0032]
【表5】 [Table 5]
【0033】[0033]
【試験例5】実施例1に示した方法で調製した各鉄飽和
度の鉄結合型ラクトフェリン及び鉄非結合型ラクトフェ
リンを試料として、サイトメガロウイルス(CMV)に
対する感染防御効果を調べた。なお、各鉄飽和度に調整
した鉄結合型ラクトフェリン及び鉄非結合型ラクトフェ
リンを2%血清添加MEM培地に5mg/mlとなるように溶
解し、0.45μm のフィルターで濾過滅菌し、ストック溶
液を必要に応じて2%血清添加MEM培地により希釈し
て用いた。ヒトCMV(Towne株) を各鉄飽和度の鉄結合
型ラクトフェリン含有培溶液(0.1mg/ml)で1時間インキ
ュベート後、ヒト胎児線維芽細胞(HEL細胞)に感染
させた。さらにラクトフェリンを含まない培養液をコン
トロールとした。24時間培養後、ヒトCMV陽性血清で
蛍光染色し細胞へのヒトCMVの吸着能力を測定した。
そして、カバースリップ当たりの蛍光陽性細胞数の平均
値を求めた。その結果を表6に示す。これによると、鉄
非結合型ラクトフェリンに比べ鉄飽和度が大きい鉄結合
型ラクトフェリン程CMV吸着侵入能力を抑制すること
が確認された。Test Example 5 The protective effect against cytomegalovirus (CMV) was examined using iron-binding lactoferrin and non-iron-binding lactoferrin of each iron saturation prepared by the method shown in Example 1 as samples. In addition, iron-bound lactoferrin and iron-free lactoferrin adjusted to each iron saturation were dissolved at a concentration of 5 mg / ml in MEM medium supplemented with 2% serum, sterilized by filtration through a 0.45 μm filter, and a stock solution was required. It was diluted with a MEM medium supplemented with 2% serum according to the above. Human CMV (Towne strain) was incubated with an iron-binding lactoferrin-containing culture solution (0.1 mg / ml) for each iron saturation for 1 hour, and then infected with human fetal fibroblasts (HEL cells). Further, a culture solution containing no lactoferrin was used as a control. After culturing for 24 hours, the cells were fluorescently stained with human CMV-positive serum, and the ability to adsorb human CMV to cells was measured.
Then, the average value of the number of fluorescence-positive cells per coverslip was determined. Table 6 shows the results. According to this, it was confirmed that the iron-bound lactoferrin having a higher iron saturation than the non-iron-bound lactoferrin suppressed the CMV adsorption invasion ability.
【0034】[0034]
【表6】 [Table 6]
【0035】[0035]
【実施例2】表7に示した配合により原料を混合した
後、打錠機で打錠して、病原性細菌及びウイルス感染防
御機能を賦与したタブレットを製造した。Example 2 After mixing the raw materials according to the formulation shown in Table 7, the mixture was tableted with a tableting machine to produce a tablet having a protective function against pathogenic bacteria and viruses.
【0036】[0036]
【表7】 ─────────────────────────────── 鉄結合型ラクトフェリン (鉄飽和度 100%) 10.0 (重量%) 還元麦芽糖 52.0 砂糖 15.0 乳糖 18.7 クエン酸 2.0 香料 1.0 滑沢剤 1.3 ───────────────────────────────[Table 7] 結合 Iron-bound lactoferrin (iron saturation 100%) 10.0 (% by weight) ) Reduced maltose 52.0 Sugar 15.0 Lactose 18.7 Citric acid 2.0 Flavor 1.0 Lubricant 1.3 ───────────────────────────────
【0037】[0037]
【実施例3】表8に示した配合により原料を混合し、容
器に充填した後、加熱殺菌して、病原性細菌及びウイル
ス感染防御機能を賦与した飲料を製造した。Example 3 Raw materials were mixed according to the formulation shown in Table 8, filled in a container, and then sterilized by heating to produce a beverage having a protective function against pathogenic bacteria and viruses.
【0038】[0038]
【表8】 ─────────────────────────────── 鉄結合型ラクトフェリン (鉄飽和度 100%) 2.0 (重量%) 果糖ブドウ糖液糖 8.0 クエン酸 0.6 リンゴ果汁 10.0 水 79.4 ───────────────────────────────[Table 8] 結合 Iron-bound lactoferrin (iron saturation 100%) 2.0 (% by weight) ) Fructose glucose liquid sugar 8.0 citric acid 0.6 apple juice 10.0 water 79.4 ───────────────────────────────
【0039】[0039]
【発明の効果】本発明の病原性細菌及びウイルス感染防
御剤や病原性細菌及びウイルス感染防御機能を賦与した
医薬及び飲食品は、病原性細菌やウイルスに対して優れ
た感染防御効果を示す。しかも鉄飽和度を高めた鉄結合
型ラクトフェリンを使用するので、比較的安価に大量供
給が可能であり、しかも、極めて安全性が高いという特
徴を有している。EFFECTS OF THE INVENTION The agent for protecting pathogenic bacteria and viruses of the present invention and the pharmaceuticals and foods and beverages imparting the function of protecting pathogenic bacteria and viruses from infection exhibit an excellent effect of protecting against pathogenic bacteria and viruses. In addition, since iron-binding lactoferrin with an increased iron saturation is used, it can be supplied in large quantities at a relatively low cost, and has a feature of extremely high safety.
Claims (4)
る病原性細菌及びウイルス感染防御剤。1. A protective agent against pathogenic bacteria and viruses comprising iron-binding lactoferrin as an active ingredient.
〜 100%である請求項1記載の感染防御剤。2. The iron-bound lactoferrin having an iron saturation of 20.
The infection protective agent according to claim 1, wherein the amount is from 100% to 100%.
性細菌及びウイルス感染防御機能を賦与した医薬又は飲
食品。3. A medicament or food or drink having an iron-binding lactoferrin compound and a protective function against pathogenic bacteria and viruses.
〜 100%である請求項3記載の医薬又は飲食品。4. An iron-bound lactoferrin having an iron saturation of 20.
The medicament or food or drink according to claim 3, wherein the amount is from 100% to 100%.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10395998A JP4306828B2 (en) | 1998-03-31 | 1998-03-31 | Protective agent against pathogenic bacteria |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10395998A JP4306828B2 (en) | 1998-03-31 | 1998-03-31 | Protective agent against pathogenic bacteria |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH11286452A true JPH11286452A (en) | 1999-10-19 |
JP4306828B2 JP4306828B2 (en) | 2009-08-05 |
Family
ID=14367941
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP10395998A Expired - Fee Related JP4306828B2 (en) | 1998-03-31 | 1998-03-31 | Protective agent against pathogenic bacteria |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP4306828B2 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008100935A (en) * | 2006-10-18 | 2008-05-01 | Morinaga Milk Ind Co Ltd | Prevotella intermedia inhibitor |
JP2011067218A (en) * | 2000-03-24 | 2011-04-07 | Meiji Milk Prod Co Ltd | Component inducing production of antibody specific to lipid a of gram-negative bacteria |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6322525A (en) * | 1986-07-15 | 1988-01-30 | Snow Brand Milk Prod Co Ltd | Hematinic |
JPS63255300A (en) * | 1987-04-10 | 1988-10-21 | Snow Brand Milk Prod Co Ltd | Method for separating and purifying lactoferrin from milk using sulfuric acid esterification product |
JPH02233619A (en) * | 1989-03-08 | 1990-09-17 | Snow Brand Milk Prod Co Ltd | Viral phylactic agent |
JPH03130060A (en) * | 1989-07-21 | 1991-06-03 | Snow Brand Milk Prod Co Ltd | Production of iron enriched drink |
JPH03220130A (en) * | 1990-01-25 | 1991-09-27 | Snow Brand Milk Prod Co Ltd | Agent inhibitory against implantation of pathogenic microorganism and food and drink or the like containing the same inhibitory agent |
JPH048269A (en) * | 1990-04-26 | 1992-01-13 | Snow Brand Milk Prod Co Ltd | Preparation of iron-reinforced beverage |
JPH04141067A (en) * | 1990-10-02 | 1992-05-14 | Morinaga Milk Ind Co Ltd | Iron agent, production of thereof and production of iron enriched food |
JPH0592927A (en) * | 1991-05-13 | 1993-04-16 | Imuno Japan:Kk | Preventive and therapeutic agent for infectious disease with pathogenic germ added to formula feed for cultured aquatic animal |
JPH06316529A (en) * | 1991-12-03 | 1994-11-15 | Imuno Japan:Kk | Pharmaceutical composition for treatment and prevention of opportunistic infection accompanying lentivirus infection |
-
1998
- 1998-03-31 JP JP10395998A patent/JP4306828B2/en not_active Expired - Fee Related
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6322525A (en) * | 1986-07-15 | 1988-01-30 | Snow Brand Milk Prod Co Ltd | Hematinic |
JPS63255300A (en) * | 1987-04-10 | 1988-10-21 | Snow Brand Milk Prod Co Ltd | Method for separating and purifying lactoferrin from milk using sulfuric acid esterification product |
JPH02233619A (en) * | 1989-03-08 | 1990-09-17 | Snow Brand Milk Prod Co Ltd | Viral phylactic agent |
JPH03130060A (en) * | 1989-07-21 | 1991-06-03 | Snow Brand Milk Prod Co Ltd | Production of iron enriched drink |
JPH03220130A (en) * | 1990-01-25 | 1991-09-27 | Snow Brand Milk Prod Co Ltd | Agent inhibitory against implantation of pathogenic microorganism and food and drink or the like containing the same inhibitory agent |
JPH048269A (en) * | 1990-04-26 | 1992-01-13 | Snow Brand Milk Prod Co Ltd | Preparation of iron-reinforced beverage |
JPH04141067A (en) * | 1990-10-02 | 1992-05-14 | Morinaga Milk Ind Co Ltd | Iron agent, production of thereof and production of iron enriched food |
JPH0592927A (en) * | 1991-05-13 | 1993-04-16 | Imuno Japan:Kk | Preventive and therapeutic agent for infectious disease with pathogenic germ added to formula feed for cultured aquatic animal |
JPH06316529A (en) * | 1991-12-03 | 1994-11-15 | Imuno Japan:Kk | Pharmaceutical composition for treatment and prevention of opportunistic infection accompanying lentivirus infection |
Non-Patent Citations (4)
Title |
---|
ANTIVIRAL RESEARCH, vol. 29, JPN4007020732, March 1996 (1996-03-01), pages 221 - 231, ISSN: 0000891625 * |
ANTIVIRAL RESEARCH, vol. 29, JPN6009018856, March 1996 (1996-03-01), pages 221 - 231, ISSN: 0001304010 * |
CANCER RESEARCH, vol. 47, JPN4007020731, 1 August 1987 (1987-08-01), pages 4184 - 4188, ISSN: 0000891624 * |
CANCER RESEARCH, vol. 47, JPN6009018855, 1 August 1987 (1987-08-01), pages 4184 - 4188, ISSN: 0001304009 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011067218A (en) * | 2000-03-24 | 2011-04-07 | Meiji Milk Prod Co Ltd | Component inducing production of antibody specific to lipid a of gram-negative bacteria |
JP2008100935A (en) * | 2006-10-18 | 2008-05-01 | Morinaga Milk Ind Co Ltd | Prevotella intermedia inhibitor |
Also Published As
Publication number | Publication date |
---|---|
JP4306828B2 (en) | 2009-08-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2631470B2 (en) | Infection protective agent | |
US5585365A (en) | Antiviral polysaccharide | |
JP3100005B2 (en) | Human immunodeficiency virus infection / growth inhibitor | |
US7858595B2 (en) | Anti-infectious carbohydrates | |
US5260280A (en) | Bacterial toxin neutralizer | |
JPH03220130A (en) | Agent inhibitory against implantation of pathogenic microorganism and food and drink or the like containing the same inhibitory agent | |
CN112351693A (en) | Anti-influenza virus agent for inhibiting severe influenza | |
Shini et al. | A comprehensive review on lactoferrin: A natural multifunctional glycoprotein | |
DK158334B (en) | Process for preparing polypeptide fractions from mussels | |
JP2000103743A (en) | Food, cosmetic and medicine containing polypeptides belonging to family having thioredoxin activity | |
JP3694319B2 (en) | Antibacterial composition containing multimeric alpha-lactalbumin | |
JPH0648955A (en) | Activator for digestive tract cell | |
KR100702885B1 (en) | Helicobacter pylori adhesion inhibitor | |
JP4014330B2 (en) | Viral infection protection agent | |
JP4306828B2 (en) | Protective agent against pathogenic bacteria | |
JP2001516570A (en) | Bifidogenic peptides | |
EP3290043B1 (en) | Enzyme-treated milk product, method for producing same, composition, and product | |
JP2787220B2 (en) | Virus infection protective agent | |
US7628976B2 (en) | Method of screening for substances which proliferate natural killer cells | |
JPH11292788A (en) | Infection preventive against helicobacter pylori | |
JP4330088B2 (en) | Tight junction permeation inhibitor | |
JP2514375B2 (en) | Baby milk powder with protection against infection | |
JP3794722B2 (en) | High molecular glycoprotein mixture derived from bovine whey having a protective action against virus infection, its use and production method thereof | |
AU711437B2 (en) | Inhibition of human rotavirus infection | |
JP3887704B2 (en) | Bacterial toxin neutralizer |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040910 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070903 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071102 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20080520 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080722 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080819 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20080822 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081023 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081222 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090421 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090428 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120515 Year of fee payment: 3 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120515 Year of fee payment: 3 |
|
R371 | Transfer withdrawn |
Free format text: JAPANESE INTERMEDIATE CODE: R371 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120515 Year of fee payment: 3 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120515 Year of fee payment: 3 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120515 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130515 Year of fee payment: 4 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130515 Year of fee payment: 4 |
|
LAPS | Cancellation because of no payment of annual fees |