CN109588604A - A kind of pinctada fucata glycosaminoglycan effervescent tablet and preparation method thereof - Google Patents
A kind of pinctada fucata glycosaminoglycan effervescent tablet and preparation method thereof Download PDFInfo
- Publication number
- CN109588604A CN109588604A CN201811344841.9A CN201811344841A CN109588604A CN 109588604 A CN109588604 A CN 109588604A CN 201811344841 A CN201811344841 A CN 201811344841A CN 109588604 A CN109588604 A CN 109588604A
- Authority
- CN
- China
- Prior art keywords
- glycosaminoglycan
- pinctada fucata
- effervescent tablet
- pinctada
- preparation
- 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.)
- Pending
Links
- 229920002683 Glycosaminoglycan Polymers 0.000 title claims abstract description 138
- 241000490568 Pinctada fucata Species 0.000 title claims abstract description 124
- 239000007938 effervescent tablet Substances 0.000 title claims abstract description 93
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 230000000694 effects Effects 0.000 claims abstract description 28
- 235000013372 meat Nutrition 0.000 claims abstract description 17
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 16
- 239000000314 lubricant Substances 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000012545 processing Methods 0.000 claims abstract description 11
- 235000015170 shellfish Nutrition 0.000 claims abstract description 11
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical group OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- 101000693530 Staphylococcus aureus Staphylokinase Proteins 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 11
- 102000004190 Enzymes Human genes 0.000 claims description 10
- 108090000790 Enzymes Proteins 0.000 claims description 10
- 239000012452 mother liquor Substances 0.000 claims description 10
- 238000004806 packaging method and process Methods 0.000 claims description 8
- 239000011122 softwood Substances 0.000 claims description 8
- 241001212699 Pinctada martensii Species 0.000 claims description 7
- 238000005119 centrifugation Methods 0.000 claims description 7
- 238000003760 magnetic stirring Methods 0.000 claims description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 7
- 238000004659 sterilization and disinfection Methods 0.000 claims description 7
- 238000009777 vacuum freeze-drying Methods 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- 108091005804 Peptidases Proteins 0.000 claims description 6
- 239000004365 Protease Substances 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 6
- 102000035195 Peptidases Human genes 0.000 claims description 5
- 238000005349 anion exchange Methods 0.000 claims description 5
- 238000005571 anion exchange chromatography Methods 0.000 claims description 5
- 230000000249 desinfective effect Effects 0.000 claims description 5
- 238000000502 dialysis Methods 0.000 claims description 5
- 229960004756 ethanol Drugs 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 5
- 230000001376 precipitating effect Effects 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 5
- 235000003599 food sweetener Nutrition 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 4
- 239000008236 heating water Substances 0.000 claims description 4
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 239000003765 sweetening agent Substances 0.000 claims description 4
- 235000020985 whole grains Nutrition 0.000 claims description 4
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 230000007071 enzymatic hydrolysis Effects 0.000 claims description 3
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 238000000748 compression moulding Methods 0.000 claims description 2
- 230000009849 deactivation Effects 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000012216 screening Methods 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 239000007767 bonding agent Substances 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 229930006000 Sucrose Natural products 0.000 claims 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims 1
- 125000005586 carbonic acid group Chemical group 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 239000005720 sucrose Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 11
- 230000036737 immune function Effects 0.000 abstract description 10
- 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 abstract description 9
- 239000008101 lactose Substances 0.000 abstract description 8
- 239000000853 adhesive Substances 0.000 abstract description 7
- 230000001070 adhesive effect Effects 0.000 abstract description 7
- 238000011161 development Methods 0.000 abstract description 5
- 239000000796 flavoring agent Substances 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 238000009360 aquaculture Methods 0.000 abstract description 2
- 244000144974 aquaculture Species 0.000 abstract description 2
- 235000019634 flavors Nutrition 0.000 abstract description 2
- 239000003205 fragrance Substances 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 210000000952 spleen Anatomy 0.000 description 18
- 229920001491 Lentinan Polymers 0.000 description 11
- 229940115286 lentinan Drugs 0.000 description 11
- 238000012360 testing method Methods 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 230000006872 improvement Effects 0.000 description 9
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 229960004397 cyclophosphamide Drugs 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- -1 Amine glycan Chemical class 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 6
- 210000000265 leukocyte Anatomy 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 241000490567 Pinctada Species 0.000 description 5
- 210000002798 bone marrow cell Anatomy 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 235000013402 health food Nutrition 0.000 description 5
- 210000000822 natural killer cell Anatomy 0.000 description 5
- 230000000242 pagocytic effect Effects 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 210000003024 peritoneal macrophage Anatomy 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 230000022534 cell killing Effects 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 239000004411 aluminium Substances 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 210000003298 dental enamel Anatomy 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 231100000682 maximum tolerated dose Toxicity 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 235000000832 Ayote Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 235000009917 Crataegus X brevipes Nutrition 0.000 description 1
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 description 1
- 235000009685 Crataegus X maligna Nutrition 0.000 description 1
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 description 1
- 235000009486 Crataegus bullatus Nutrition 0.000 description 1
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 description 1
- 235000009682 Crataegus limnophila Nutrition 0.000 description 1
- 235000004423 Crataegus monogyna Nutrition 0.000 description 1
- 240000000171 Crataegus monogyna Species 0.000 description 1
- 235000002313 Crataegus paludosa Nutrition 0.000 description 1
- 235000009840 Crataegus x incaedua Nutrition 0.000 description 1
- 240000004244 Cucurbita moschata Species 0.000 description 1
- 235000009854 Cucurbita moschata Nutrition 0.000 description 1
- 235000009804 Cucurbita pepo subsp pepo Nutrition 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000879903 Pteria Species 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 206010049040 Weight fluctuation Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000010669 acid-base reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 231100000460 acute oral toxicity Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000000600 disaccharide group Chemical group 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002766 immunoenhancing effect Effects 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 238000011566 inbred mouse model Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 235000015136 pumpkin Nutrition 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 239000013535 sea water Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical group 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 1
- 235000019408 sucralose Nutrition 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Classifications
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/385—Concentrates of non-alcoholic beverages
- A23L2/39—Dry compositions
- A23L2/395—Dry compositions in a particular shape or form
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/40—Effervescence-generating compositions
-
- 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0066—Isolation or extraction of proteoglycans from organs
-
- 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
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The present invention relates to a kind of pinctada fucata glycosaminoglycan effervescent tablets and preparation method thereof, include following components in percentage by weight: pinctada fucata glycosaminoglycan 15%-25%, disintegrating agent 30%-40%, adhesive 1%-3%, lubricant 1%-3%, corrigent 2%-4%, surplus are lactose.Pinctada fucata glycosaminoglycan effervescent tablet piece type prepared by the present invention is that biplane is round, shape is clean and tidy, surface is smooth, and color is white, uniformity, meets water and is disintegrated rapidly and generates bulk gas, mouthfeel is soft, free from admixture, has distinctive fragrance and flavour, and organoleptic quality is good, it has no toxic side effect, helps to maintain the normal immune function of body.The method of the present invention process operability is strong, low in cost, is suitble to industrialized production, provides technological innovation for the application of pinctada fucata glycosaminoglycan and the high-valued exploitation of shellfish meat, significant to the development of promotion pearl aquaculture and processing industry.
Description
Technical field
The present invention relates to health food processing technique field, in particular to a kind of pinctada fucata glycosaminoglycan effervescent tablet and
Preparation method.
Background technique
Pinctada fucata Pinctada fucata martensii (Dunker) also known as pteria martensii, are south Chinas
The principal item of seawater pearl culture is distributed in Guangdong, Guangxi and Hainan coastal area.Pinctada fucata is in addition to being rich in high-quality egg
Except white matter and several mineral materials, glycosaminoglycan in the middle is also especially noticeable.Glycosaminoglycan
(Glycosaminoglycans, GAGs), also referred to as glycosaminoglycan or acid mucopolysaccharide are the length being made of duplicate disaccharide unit
Chain polysaccharide is present in the tissue of most marine animals, and structure and property are different from known terrestrial plant polysaccharide, are reported
Road has a variety of effects such as enhancing immune function, anticoagulation, hypoglycemic, antitumor.According to the literature, glycosaminoglycan can stimulate machine
Maturation, differentiation and the breeding of the various immunocompetent cells (Dendritic Cells, bone-marrow-derived lymphocyte) of body increase the non-spy of macrophage
Specific cell poison, the generation of cell factors and the tables of cytokine receptor such as induction IL-1, IL-2, TNF-α, IFN-γ, IL-8
It reaches, antigen submission, antibody is promoted to be formed, the effects of the classical pathway and change approach of complement activation system.Pinctada fucata sugar
Amine glycan is a kind of natural bioactive polysaccharide with immunoloregulation function, mainly by D- Glucosamine, D- ammonia
The monosaccharide such as base glucuronic acid, glucose, mannose, galactolipin, xylose, fucose are constituted.
After pearl is adopted in pearl agriculture, annual remaining about 3500-4000 tons of processing byproduct pearl oyster meat, is mostly fresh or thick
Eaten after processing, sold with fresh goods based on, it is cheap (about 5-10 member/kg), in Guangdong Leizhou City and Xuwen County, Beihai Fisheries Base Guangxi Province
The ground such as city, Hainan cause the huge waste of resource, and deep processing rate is lower, and preservation term is short, easily putrid and deteriorated, lead to pearl oyster meat
Development and utilization are restricted.
As 103039792A patent application discloses " it is a kind of for enhance immune glycosaminoglycan from Pinctada martensii soft capsule and its
Preparation method ", technique are that nacre whole viscera homogenate enzymatic hydrolysis, centrifugation alcohol precipitation, dry the glycosaminoglycan of washing and are added auxiliary
Soft capsule is made in material.But the defect of the above method is: before pearl oyster meat is without adding flooding sofening treatment, through testing
Card, thick glycosaminoglycan purity obtained is only 30%-45%, the too low immunoenhancement result that will affect obtained product of purity.
Effervescent tablet is a kind of tablet containing Effervescent tablet disintegration agent.Disintegrating agent is usually organic acid and sodium carbonate, bicarbonate
The mixture of sodium, into the water after, acid-base reactions occur for two kinds of substances, generate great amount of carbon dioxide, make tablet be disintegrated rapidly with
Melt, the bubble for being disintegrated generation makes tablet rolling up and down in water, accelerates it to be disintegrated and melt, is partially dissolved in drinking-water, makes
When drinking-water is drunk in entrance, there is the aesthetic feeling as carbonated drink, liked by the current young consumer group, is a kind of novel solid drink
Material.Effervescent tablet originates in pharmaceutical field, has many advantages, such as that rapid-action, utilization rate is high, easy to carry, at present to field of food
Development, such as pumpkin corn powder effervescent tablet, hawthorn effervescent tablet, effervescent tea tablet.Under the premise of pinctada fucata resource complete utilization
Pinctada fucata glycosaminoglycan effervescent tablet is developed, it can be maximum while effectively supplement pinctada fucata glycosaminoglycan function factor
The extra large fishy smell for reducing to limit pinctada fucata shellfish meat itself, enhances agreeable to the taste sense, for people healthy living provide it is a kind of novel
Pinctada fucata glycosaminoglycan health food.
Summary of the invention
The first purpose of the invention is to provide a kind of pinctada fucata glycosaminoglycan effervescent tablet, can help to remain normal
Immune function is convenient for carrying, and breaches traditional limitation of existing pinctada fucata food development form, and solves Hepu pearl oyster
The lower problem of shellfish shellfish meat higher value application rate.
A second object of the present invention is to provide the preparation method of above-mentioned pinctada fucata glycosaminoglycan effervescent tablet, this method
The product of being made purity is high, it is simple and easy, it is suitble to industrialized production.
Solving technical solution used by first purpose of the invention is:
A kind of pinctada fucata glycosaminoglycan effervescent tablet, it includes following weight percent meter components:
The disintegrating agent is sodium bicarbonate and citric acid, preferably, the proportion of the sodium bicarbonate and citric acid is 2:
1。
Described adhesive is 10% polyvinylpyrrolidone ethanol solution.Because experiment uses soda acid mixing granulation technique, need
Strict control contact wetting, so the polyvinylpyrrolidone (PVP) that selection dissolves in dehydrated alcohol makees adhesive
The lubricant is PEG4000.Since mobility of particle is bad when to avoid film-making, there is slice weight fluctuation greatly, out
Lubricant will be added in phenomenons, the particles such as piece is difficult, finish is low before tabletting.Soluble oil PEG 4000 collapses effervescent tablet
Clarity after solution is without influence, and lubricity and resistance to bond are preferable, preferably select
The corrigent includes 0.1% essence, and surplus is sweetener, preferably, the sweetener is Sucralose.
Solving technical solution used by second purpose of the invention is:
A kind of preparation method of pinctada fucata glycosaminoglycan effervescent tablet comprising following steps:
S1, add flooding after taking pinctada fucata meat tissue to be homogenized, adjust pH to 7.0-7.6, add neutral proteinase and pancreas
Protease composite enzyme is digested, centrifuging and taking supernatant after enzyme deactivation, obtains pinctada fucata glycosaminoglycan mother liquor；
S2, gained pinctada fucata glycosaminoglycan mother liquor is subjected to alcohol precipitation processing, precipitating is filtered and washed after centrifugation, freezed
Dry thick glycosaminoglycan；
S3, thick glycosaminoglycan is taken, after anion exchange chromatography, dialysis concentration is freeze-dried to obtain pinctada fucata sugar
Amine glycan；
S4, it screens, then sprays after taking pinctada fucata glycosaminoglycan and disintegrating agent, diluent to be mixed evenly in proportion
Adhesive softwood is granulated, and is added corrigent, lubricant, after mixing after dry, whole grain, compression molding, after sterilization packaging
Obtain pinctada fucata glycosaminoglycan effervescent tablet finished product.In the present invention, diluent is lactose.
Further, the solid-liquid ratio that flooding is added in the step S1 is 1:2,45-55 DEG C under magnetic stirring apparatus effect
Heating water bath 4-6h.
The pH of 0.1mol/L sodium hydrate regulator solution is used in the step S1.
The amount of neutral proteinase and trypsase complex enzyme is that 10- is added in every gram of pinctada fucata shellfish meat in the step S1
The mass ratio of 15mg, neutral proteinase and trypsase is 7:8.
In the step S1, enzymatic hydrolysis 45-55 DEG C of heating water bath 4h under magnetic stirring apparatus effect.
Destroy the enzyme treatment is the inactivated proteases 10min in 100 DEG C of water-baths in the step S1, is cooled to room temperature；It is described from
Heart processing is that 8000-12000rpm is centrifuged 15-20min.
Further, alcohol precipitation processing is in the step S2 plus dehydrated alcohol is to final concentration 75%, precipitates 8-12h at 4 DEG C.
Centrifugation is with 10000-12000rpm centrifugation 15-20min in the step S2；Washing is precipitated as with dehydrated alcohol-
Acetone alternately washing 4-5 times.
Freeze-drying is in 0.030~0.035kPa, -50~-55 DEG C of vacuum freezedrying 12-36h in the step S2.
Further, anion exchange chromatography is using DEAE-52 anion-exchange column to raw sugar in the step S3
Amine glycan is purified, applied sample amount 10mL, and flow velocity 1mL/min, every pipe collects 10mL, and mobile phase is respectively pure water, 0.5mol/
mLNaAc、1.5mol/mLNaCl。
Dialysis concentration is to be dialysed for 24 hours with the bag filter of molecular cut off 8KD-14KD in the step S3.
Freeze-drying is in 0.030~0.035kPa, -50~-55 DEG C of vacuum freezedrying 12-36h in the step S3.
Further, in the step S4 screening to sieve with 100 mesh sieve, be granulated for 16 meshes, whole grain be 20 meshes.
Drying is dried to moisture content lower than 0.5% in the step S4 under the conditions of being 60-70 DEG C.
Sterilizing is using ultraviolet disinfecting machine progress ultraviolet-sterilization in the step S4.
The mesh number requirement of step S4, has an impact to tablet molding and fater disintegration.
The beneficial effects of the present invention are:
1) before carrying out enzymolysis processing, hot water extraction first is carried out to raw material, volume of material is expanded, makes albumen in raw material
The prototype structure part of matter changes, and can save enzymolysis time, save foreign protein in enzyme dosage, more preferably removing finished product.
2) anion exchange chromatography, bag filter dialysis purification glycosaminoglycan is added in the present invention, reaches obtained product purity
85% or more, there is huge promotion compared to the purification purity without extraction, is a kind of glycosaminoglycan extraction of raising to greatest extent
The new process of rate.
3) pinctada fucata glycosaminoglycan effervescent tablet prepared by the present invention is biplane circular piece type, and surface is smooth, color
White, uniformity meets water and is disintegrated and generates bulk gas rapidly, has distinctive fragrance and flavour, and action temperature and nothing
Toxic side effect has apparent health-care efficacy, helps to maintain the normal immune function of human organism.
4) preparation method is simple for pinctada fucata glycosaminoglycan effervescent tablet of the present invention, is suitble to industrialized production, favorably
In solving the problems, such as pinctada fucata higher value application, the wasting of resources is avoided, while solving environmental pollution caused by shellfish meat abandons
Problem promotes the sustainable and healthy development of pearl aquaculture and secondary industry.
Detailed description of the invention
Fig. 1 is histogram of the pinctada fucata glycosaminoglycan effervescent tablet to the protective effect of spleen；
Fig. 2 is the histogram of the effect of pinctada fucata glycosaminoglycan effervescent tablet Number of Peripheral Blood Leucocyte；
Fig. 3 is histogram of the pinctada fucata glycosaminoglycan effervescent tablet to the effect of bone marrow cell；
Fig. 4 is histogram of the pinctada fucata glycosaminoglycan effervescent tablet to the effect of spleen lymphocyte proliferation ability；
Fig. 5 is histogram of the pinctada fucata glycosaminoglycan effervescent tablet to the effect of spleen NK cell activity；
Fig. 6 is histogram of the pinctada fucata glycosaminoglycan effervescent tablet to the effect of peritoneal macrophage phagocytic activity；
Fig. 7 is histogram of the pinctada fucata glycosaminoglycan effervescent tablet to the effect of serum IL-2 level.
Specific embodiment
Technical solution of the present invention is described further with reference to the accompanying drawings and examples, so that those skilled in the art
The present invention can be better understood and can be practiced, but illustrated embodiment is not as a limitation of the invention.
Embodiment 1
A kind of pinctada fucata glycosaminoglycan effervescent tablet for helping to maintain normal immunological function, the effervescent tablet slice weight are
202.3mg ± 2.8mg comprising pinctada fucata glycosaminoglycan 25%, disintegrating agent 36%, adhesive 2.5%, lubricant 2%, is rectified
Taste agent 3%, surplus are lactose.
The preparation method of pinctada fucata glycosaminoglycan effervescent tablet in the present embodiment, comprising the following steps:
(1) pinctada fucata meat tissue 2568g is taken, flooding is added for 1:2 with solid-liquid ratio after homogenate, is made in magnetic stirring apparatus
With lower 50 DEG C of water bath with thermostatic control 5h, with the pH to 7.6 of the sodium hydrate regulator solution of 0.1mol/L；With every gram of pinctada fucata shellfish meat
15mg neutral proteinase and trypsase combined hydrolysis (mass ratio of neutral proteinase and trypsase is 7:8) is added, in magnetic
Power blender acts on lower 50 DEG C of water-bath 4h.After in 100 DEG C of water-baths inactivated proteases 10min, be cooled to room temperature,
11000rpm is centrifuged 15min, collects supernatant, obtains pinctada fucata glycosaminoglycan mother liquor；
(2) add dehydrated alcohol to final concentration 75% in gained pinctada fucata glycosaminoglycan mother liquor, precipitate 8h at 4 DEG C, then
It is centrifuged 15min with 11000rpm, precipitating dehydrated alcohol-acetone alternately washing 4 times, in 0.032kPa, -52 DEG C of freezing vacuums are dry
Dry to obtain thick glycosaminoglycan 33.51g for 24 hours, crude product yield is 1.30%；
(3) the thick glycosaminoglycan for taking step (2) purifies thick glycosaminoglycan using DEAE-52 anion-exchange column,
Applied sample amount 10mL, flow velocity 1mL/min, every pipe collect 10mL, and mobile phase is respectively pure water, 0.5mol/mLNaAc, 1.5mol/
MLNaCl is dialysed for 24 hours with the bag filter of molecular cut off 10KD, is closed in 0.032kPa, -52 DEG C of vacuum freezedrying 28h
Pu glycosaminoglycan from Pinctada martensii 13.47g, highly finished product yield are 0.525%, and purity is up to 86.9%；
(4) 100 mesh are crossed after pinctada fucata glycosaminoglycan and disintegrating agent, lactose being mixed evenly according to the above ratio
Sieve, the polyvinylpyrrolidone ethanol solution of mass concentration 10% is slowly sprayed to mixed raw material, while constantly stirring by 2mL/10g
It mixes uniformly, neither too hard, nor too soft softwood is made, cross 16 meshes, so that softwood is become particle, manufactured wet granular is spread in enamel tray
In, it is dried to moisture content under the conditions of 65 DEG C lower than 0.5% hereinafter, being crushed with pulverizer, crosses 20 meshes, mass fraction is added
2% lubricant and 3% corrigent carry out ultraviolet-sterilization using ultraviolet disinfecting machine, using double with single-punch tablet press tabletting
Pinctada fucata glycosaminoglycan effervescent tablet 210, slice weight 202.3mg is made by the specification packaging of 10 every plates in aluminium packaging altogether
± 2.8mg, the every 50.58mg of glycosaminoglycan containing pinctada fucata.
According to the regulation of GB 16740-2014 national food safety standard health food, gained final product quality index such as table 1
It is shown, meet the requirements.
The detection of 1 pinctada fucata glycosaminoglycan effervescent tablet quality index of table
Embodiment 2
A kind of pinctada fucata glycosaminoglycan effervescent tablet for helping to maintain normal immunological function, the effervescent tablet slice weight are
198.6mg ± 2.4mg includes pinctada fucata glycosaminoglycan 20%, disintegrating agent 33%, adhesive 2%, lubricant 2%, flavoring
Agent 3%, surplus are lactose.
The preparation method of pinctada fucata glycosaminoglycan effervescent tablet in the present embodiment, comprising the following steps:
(1) pinctada fucata meat tissue 2714g is taken, flooding is added for 1:2 with solid-liquid ratio after homogenate, is made in magnetic stirring apparatus
With lower 55 DEG C of water bath with thermostatic control 4h, with the pH to 7.2 of the sodium hydrate regulator solution of 0.1mol/L；With every gram of pinctada fucata shellfish meat
12mg neutral proteinase and trypsase combined hydrolysis (mass ratio of neutral proteinase and trypsase is 7:8) is added, in magnetic
Power blender acts on lower 55 DEG C of water-bath 4h.After in 100 DEG C of water-baths inactivated proteases 10min, be cooled to room temperature,
10000rpm is centrifuged 20min, collects supernatant, obtains pinctada fucata glycosaminoglycan mother liquor；
(2) add dehydrated alcohol to final concentration 75% in gained pinctada fucata glycosaminoglycan mother liquor, precipitate 12h at 4 DEG C, then
It is centrifuged 20min with 10000rpm, precipitating dehydrated alcohol-acetone alternately washing 4 times, in 0.031kPa, -54 DEG C of freezing vacuums are dry
Dry 30h obtains thick glycosaminoglycan 40.31g, and crude product yield is 1.49%, and purity is up to 89.2%；
(3) the thick glycosaminoglycan for taking step (2) purifies thick glycosaminoglycan using DEAE-52 anion-exchange column,
Applied sample amount 10mL, flow velocity 1mL/min, every pipe collect 10mL, and mobile phase is respectively pure water, 0.5mol/mLNaAc, 1.5mol/
MLNaCl is dialysed for 24 hours with the bag filter of molecular cut off 12KD, and in 0.032kPa, -51 DEG C of vacuum freezedryings are closed for 24 hours
Pu glycosaminoglycan from Pinctada martensii 16.19g, highly finished product yield are 0.600%；
(4) 100 mesh are crossed after pinctada fucata glycosaminoglycan and disintegrating agent, lactose being mixed evenly according to the above ratio
Sieve, the polyvinylpyrrolidone ethanol solution of mass concentration 10% is slowly sprayed to mixed raw material, while constantly stirring by 2mL/10g
It mixes uniformly, neither too hard, nor too soft softwood is made, cross 16 meshes, so that softwood is become particle, manufactured wet granular is spread in enamel tray
In, it is dried to moisture content under the conditions of 65 DEG C lower than 0.5% hereinafter, being crushed with pulverizer, crosses 20 meshes, mass fraction is added
2% lubricant and 3% corrigent carry out ultraviolet-sterilization using ultraviolet disinfecting machine, using double with single-punch tablet press tabletting
Pinctada fucata glycosaminoglycan effervescent tablet 230, slice weight 198.6mg is made by the specification packaging of 10 every plates in aluminium packaging altogether
± 2.4mg, the every 39.72mg of glycosaminoglycan containing pinctada fucata.
According to the regulation of GB 16740-2014 national food safety standard health food, gained final product quality index such as table 2
It is shown, meet the requirements.
The detection of 2 pinctada fucata glycosaminoglycan effervescent tablet quality index of table
Embodiment 3
A kind of pinctada fucata glycosaminoglycan effervescent tablet for helping to maintain normal immunological function, the effervescent tablet slice weight are
205.1mg ± 4.0mg includes pinctada fucata glycosaminoglycan 20%, disintegrating agent 39%, adhesive 3%, lubricant 3%, flavoring
Agent 4%, surplus are lactose.
The preparation method of pinctada fucata glycosaminoglycan effervescent tablet in the present embodiment, comprising the following steps:
(1) pinctada fucata meat tissue 2618g is taken, flooding is added for 1:2 with solid-liquid ratio after homogenate, is made in magnetic stirring apparatus
With lower 50 DEG C of water bath with thermostatic control 6h, with the pH to 7.4 of the sodium hydrate regulator solution of 0.1mol/L；With every gram of pinctada fucata shellfish meat
10mg neutral proteinase and trypsase combined hydrolysis (mass ratio of neutral proteinase and trypsase is 7:8) is added, in magnetic
Power blender acts on lower 50 DEG C of water-bath 4h.After in 100 DEG C of water-baths inactivated proteases 10min, be cooled to room temperature,
12000rpm is centrifuged 15min, collects supernatant, obtains pinctada fucata glycosaminoglycan mother liquor；
(2) add dehydrated alcohol to final concentration 75% in gained pinctada fucata glycosaminoglycan mother liquor, precipitate 12h at 4 DEG C, then
It is centrifuged 15min with 12000rpm, precipitating dehydrated alcohol-acetone alternately washing 4 times, in 0.034kPa, -52 DEG C of freezing vacuums are dry
Dry 36h obtains thick glycosaminoglycan 38.11g, and crude product yield is 1.46%, and purity is up to 88.5%；
(3) the thick glycosaminoglycan for taking step (2) purifies thick glycosaminoglycan using DEAE-52 anion-exchange column,
Applied sample amount 10mL, flow velocity 1mL/min, every pipe collect 10mL, and mobile phase is respectively pure water, 0.5mol/mLNaAc, 1.5mol/
MLNaCl is dialysed for 24 hours with the bag filter of molecular cut off 10KD, is closed in 0.032kPa, -53 DEG C of vacuum freezedrying 20h
Pu glycosaminoglycan from Pinctada martensii 13.87g, highly finished product yield are 0.530%；
(4) 100 mesh are crossed after pinctada fucata glycosaminoglycan and disintegrating agent, lactose being mixed evenly according to the above ratio
Sieve, the polyvinylpyrrolidone ethanol solution of mass concentration 10% is slowly sprayed to mixed raw material, while constantly stirring by 2mL/10g
It mixes uniformly, neither too hard, nor too soft softwood is made, cross 16 meshes, so that softwood is become particle, manufactured wet granular is spread in enamel tray
In, it is dried to moisture content under the conditions of 70 DEG C lower than 0.5% hereinafter, being crushed with pulverizer, crosses 20 meshes, mass fraction is added
3% lubricant and 4% corrigent carry out ultraviolet-sterilization using ultraviolet disinfecting machine, using double with single-punch tablet press tabletting
Pinctada fucata glycosaminoglycan effervescent tablet 190, slice weight 205.1mg is made by the specification packaging of 10 every plates in aluminium packaging altogether
± 4.0mg, the every 41.02mg of glycosaminoglycan containing pinctada fucata.
According to the regulation of GB 16740-2014 national food safety standard health food, gained final product quality index such as table 3
It is shown, meet the requirements.
The detection of 3 pinctada fucata glycosaminoglycan effervescent tablet quality index of table
The adjusting of immune function is made in order to verify pinctada fucata glycosaminoglycan effervescent tablet obtained in above-described embodiment
With and its safety above-mentioned implementation observed by building immunological function repression mouse model and oral acute toxicity rat model
Influence and Acute oral tox-hty test of the product to immune organ, immunocyte and cell factor etc. are made in example.
According to glycosaminoglycan active evaluation test result early period and adult-mouse dose reduction formula, pinctada fucata sugar
The mouse effective dose of amine glycan is 0.25mg/d, is adult effective dose 100mg/d according to formula scales, is equivalent to two panels bubble
Rise the GAG content of piece.
Pinctada fucata glycosaminoglycan effervescent tablet obtained in embodiment 1 is selected, is constructed using routine experiment method immune
Function inhibitio Balb/c inbred mouse model (SPF grades, half male and half female, weight 16-18g), 60 Balb/c mouse are random
It is divided into 6 test groups, glycosaminoglycan effervescent tablet low dosage (0.125mg/d), middle dosage (0.25mg/d), high dose is respectively set
(0.5mg/d) three groups stomach-filling given the test agent 21 days, are seen totally using lentinan film (0.25mg/d) as positive controls
It examines and influence of the product to immune organ, immunocyte and cell factor etc. is made in example 1.
Test data result is as follows:
1) protective effect of the pinctada fucata glycosaminoglycan effervescent tablet to spleen
As shown in Figure 1, cyclophosphamide causes seriously to damage to mouse spleen compared with Normal group, cause spleen etc.
The weight saving of immune organ illustrates model construction success (P < 0.01).Compared with model group, lentinan film, Hepu pearl oyster
Shellfish glycosaminoglycan effervescent tablet low dose group (0.125mg/d), middle dose group (0.25mg/d) and high dose group (0.5mg/d) are right
Mouse spleen damage has improvement result (P < 0.05), illustrates lentinan film and pinctada fucata glycosaminoglycan effervescent tablet to ring phosphorus
Spleen atrophy caused by amide all has apparent improvement.Glycosaminoglycan effervescent tablet low dose group (0.125mg/d), middle dose
Dose-effect relationship (P < 0.05) is presented in amount group (0.25mg/d), high dose group (0.5mg/d), but compared with normal group, each group is not
It is horizontal (P < 0.01) to be restored to Normal group.
In Fig. 1: normal group of * P < 0.05and**P < 0.01vs., #P < 0.05and##P < 0.01vs. model group (n=10)
(same in following figure)
2) effect of pinctada fucata glycosaminoglycan effervescent tablet Number of Peripheral Blood Leucocyte
As shown in Fig. 2, cyclophosphamide seriously reduces mouse peripheral blood leucocyte level compared with normal group, illustrate mould
Type constructs successfully (P < 0.01).Compared with model group, lentinan film, pinctada fucata glycosaminoglycan effervescent tablet low dose group
(0.125mg/d), middle dose group (0.25mg/d), high dose group (0.5mg/d) are under mouse peripheral blood leucocyte level
Drop has improvement result (P < 0.05), illustrates that it can be such that peripheral white blood cells level restores, shows lentinan film, pinctada fucata
Glycosaminoglycan effervescent tablet plays a protective role for the reduction of leucocyte.Pinctada fucata glycosaminoglycan effervescent tablet low dose group
(0.125mg/d), middle dose group (0.25mg/d), high dose group (0.5mg/d) present dose-effect relationship (P < 0.05), but with it is normal
Group is compared, and it is horizontal (P < 0.05) that each group does not recover to Normal group.
3) effect of the pinctada fucata glycosaminoglycan effervescent tablet to bone marrow cell
As shown in figure 3, cyclophosphamide causes seriously to damage to bone marrow cells in mice compared with normal group, illustrate model structure
Build up function (P < 0.01).Compared with model group, lentinan film, pinctada fucata glycosaminoglycan effervescent tablet low dose group
(0.125mg/d), middle dose group (0.25mg/d), high dose group (0.5mg/d) have improvement to make bone marrow cells in mice damage
With (P < 0.01).Pinctada fucata glycosaminoglycan effervescent tablet low dose group (0.125mg/d), middle dose group (0.25mg/d), height
Dose-effect relationship (P < 0.05) is presented in dosage group (0.5mg/d), and compared with normal group, high dose group (0.5mg/d) has been restored to
It is normal to organize horizontal (P > 0.05).
4) effect of the pinctada fucata glycosaminoglycan effervescent tablet to spleen lymphocyte proliferation ability
As shown in figure 4, cyclophosphamide causes seriously to damage to mice spleen lymphocytes proliferation ability compared with normal group,
Illustrate model construction success (P < 0.01).Compared with model group, lentinan film, low dose of pinctada fucata glycosaminoglycan effervescent tablet
Amount group (0.125mg/d), middle dose group (0.25mg/d), high dose group (0.5mg/d) are to mice spleen lymphocytes proliferation energy
The reduction of power has improvement result (P < 0.05).Pinctada fucata glycosaminoglycan effervescent tablet low dose group (0.125mg/d), middle dosage
Dose-effect relationship (P < 0.05) is presented in group (0.25mg/d), high dose group (0.5mg/d), but compared with normal group, each group is not extensive
It is horizontal (P < 0.01) that Normal group is arrived again.
5) effect of the pinctada fucata glycosaminoglycan effervescent tablet to spleen NK cell killing activity
As shown in figure 5, cyclophosphamide causes seriously to damage to mice spleen NK cell killing activity compared with normal group, say
Bright model construction success (P < 0.01).Compared with model group, lentinan film, pinctada fucata glycosaminoglycan effervescent tablet low dosage
Group (0.125mg/d), middle dose group (0.25mg/d), high dose group (0.5mg/d) are to mice spleen NK cell killing activity
Reduction has improvement result (P < 0.01).Pinctada fucata glycosaminoglycan effervescent tablet low dose group (0.125mg/d), middle dose group
Dose-effect relationship (P < 0.05) is presented in (0.25mg/d), high dose group (0.5mg/d) group, but compared with normal group, each group is not extensive
It is horizontal (P < 0.01) that Normal group is arrived again.
6) effect of the pinctada fucata glycosaminoglycan effervescent tablet to peritoneal macrophage phagocytic activity
As shown in fig. 6, cyclophosphamide causes seriously to damage to Turnover of Mouse Peritoneal Macrophages phagocytic activity compared with normal group
Wound illustrates model construction success (P < 0.01).Compared with model group, lentinan film, pinctada fucata glycosaminoglycan effervescent tablet
Low dose group (0.125mg/d), middle dose group (0.25mg/d), high dose group (0.5mg/d) are to Turnover of Mouse Peritoneal Macrophages
The reduction of phagocytic activity has improvement result (P < 0.05).Pinctada fucata glycosaminoglycan effervescent tablet low dose group (0.125mg/d),
Dose-effect relationship (P < 0.05) is presented in middle dose group (0.25mg/d), high dose group (0.5mg/d), but compared with normal group, each group
It is horizontal (P < 0.01) that Normal group is not recovered to.
7) effect of the pinctada fucata glycosaminoglycan effervescent tablet to serum IL-2 level
As shown in fig. 7, cyclophosphamide causes seriously to damage to mice serum IL-2 level compared with normal group, illustrate mould
Type constructs successfully (P < 0.01).Compared with model group, lentinan film, pinctada fucata glycosaminoglycan effervescent tablet middle dose group
(0.25mg/d), high dose group (0.5mg/d) have improvement result (P < 0.01) to the reduction of mice serum IL-2 level.Hepu
Glycosaminoglycan from Pinctada martensii effervescent tablet low dose group (0.125mg/d), middle dose group (0.25mg/d), high dose group (0.5mg/d)
It presents dose-effect relationship (P < 0.05), but compared with normal group, it is horizontal (P < 0.01) that each group does not recover to Normal group.
8) conclusion
After three weeks by stomach-filling given the test agent, pinctada fucata glycosaminoglycan effervescent tablet is to immune suppression caused by cyclophosphamide
Dose-dependent positive correlation effect is presented in system, and middle dosage (0.25mg/d) is that effective dose (is people according to body surface area conversion
Effective dose be 100mg/d), specific manifestation are as follows: accelerate index and spleen index, peripheral white blood cell and bone marrow cell it is extensive
It is multiple, enhance spleen lymphocyte proliferation and conversion capability, spleen NK cell killing activity and peritoneal macrophage phagocytic activity, increases blood
Clear IL-2 is horizontal, while can also preferably improve the quality of life of mouse.Compared with lentinan film, pinctada fucata osamine is poly-
The immunoregulation effect of sugared effervescent tablet is suitable, works gentle, has improvement result to multiple indexs, be applicable to sub-health population
The raising of immunity of organisms.
Acute oral tox-hty test refers to that primary or the interior test repeatedly contaminated for 24 hours, the main half for measuring tested material cause
Dead amount or concentration, and observe the poisoning manifestations of experimental animal.In the test, pinctada fucata glycosaminoglycan effervescent tablet group, solvent
Each 20 SD rats of control group are giving tested material process and in the 14d observation period, rat expression behaviour, activity situation, breathing, appearance
Gesture etc. is showed no exception, no rats death.After zootomy, heart, liver, spleen, stomach, intestines, kidney and the life of rat are visually observed
The internal organs such as gland shape, color, size and ratio are grown, any exception is showed no, lesion does not occur for Rats Organs and Tissues.Rat weight is just
Often increase, the rat weight of pinctada fucata glycosaminoglycan effervescent tablet group is equal compared with solvent control group in each minute point
There was no significant difference (P > 0.05), as shown in table 4.Therefore, under the experimental condition, pinctada fucata glycosaminoglycan effervescent tablet pair
SD rat oral maximum tolerated dose (MTD) is higher than 15g/kg, and toxicity grading is nontoxic.
Table 4SD rat peroral acute toxicity tests weight result
It is not limiting the scope of the present invention with the above embodiment of the present invention, embodiments of the present invention are unlimited
In this, all this kind above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modifications of other diversified forms that above structure of the present invention is made, replacement or
Change, should all fall within the scope and spirit of the invention.
Claims (20)
1. a kind of pinctada fucata glycosaminoglycan effervescent tablet, which is characterized in that include following weight percent meter component:
2. pinctada fucata glycosaminoglycan effervescent tablet according to claim 1, which is characterized in that the disintegrating agent is carbonic acid
The proportion of hydrogen sodium and citric acid, the sodium bicarbonate and citric acid is 2:1.
3. pinctada fucata glycosaminoglycan effervescent tablet according to claim 1, which is characterized in that the lubricant is
PEG4000。
4. pinctada fucata glycosaminoglycan effervescent tablet according to claim 1-3, which is characterized in that the bonding
Agent is 10% polyvinylpyrrolidone ethanol solution.
5. pinctada fucata glycosaminoglycan effervescent tablet according to claim 1, which is characterized in that the corrigent includes
0.1% essence, surplus are sweetener.
6. pinctada fucata glycosaminoglycan effervescent tablet according to claim 5, which is characterized in that the sweetener is three
Chlorine sucrose.
7. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 1-6, feature exist
In, comprising the following steps:
S1, add flooding after taking pinctada fucata meat tissue to be homogenized, adjust pH to 7.0-7.6, add neutral proteinase and tryptose
Enzyme complex enzyme is digested, centrifuging and taking supernatant after enzyme deactivation, obtains pinctada fucata glycosaminoglycan mother liquor；
S2, gained pinctada fucata glycosaminoglycan mother liquor is subjected to alcohol precipitation processing, precipitating is filtered and washed after centrifugation, be freeze-dried
Obtain thick glycosaminoglycan；
S3, take thick glycosaminoglycan, after anion exchange chromatography, dialysis concentration, be freeze-dried pinctada fucata osamine is poly-
Sugar；
S4, it is screened after taking pinctada fucata glycosaminoglycan and disintegrating agent, diluent to be mixed evenly in proportion, then sprays bonding
Agent softwood is granulated, and is added corrigent, lubricant, after mixing after dry, whole grain, compression molding, must be closed after sterilization packaging
Pu glycosaminoglycan from Pinctada martensii effervescent tablet finished product.
8. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 7, which is characterized in that the step
In rapid S1 plus the solid-liquid ratio of flooding is 1:2, the 45-55 DEG C of heating water bath 4-6h under magnetic stirring apparatus effect.
9. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 7 or 8, which is characterized in that institute
Stating the amount of neutral proteinase and trypsase complex enzyme in step S1 is that 10-15mg is added in every gram of pinctada fucata shellfish meat, described
The mass ratio of neutral proteinase and trypsase is 7:8.
10. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 9, which is characterized in that described
Enzymatic hydrolysis 45-55 DEG C of heating water bath 4h under magnetic stirring apparatus effect in step S1.
11. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 10, which is characterized in that described
Destroy the enzyme treatment is the inactivated proteases 10min in 100 DEG C of water-baths in step S1, is cooled to room temperature；The centrifugal treating is 8000-
12000rpm is centrifuged 15-20min.
12. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 7 or 11, which is characterized in that
Alcohol precipitation processing is in the step S2 plus dehydrated alcohol is to final concentration 75%, precipitates 8-12h at 4 DEG C.
13. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 12, which is characterized in that described
Centrifugation is with 10000-12000rpm centrifugation 15-20min in step S2；Washing is precipitated as alternately being washed with dehydrated alcohol-acetone
4-5 times.
14. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 13, which is characterized in that described
Freeze-drying is in 0.030~0.035kPa, -50~-55 DEG C of vacuum freezedrying 12-36h in step S2.
15. special according to the preparation method of the described in any item pinctada fucata glycosaminoglycan effervescent tablets of claim 7,11,14
Sign is that anion exchange chromatography is to carry out using DEAE-52 anion-exchange column to thick glycosaminoglycan in the step S3
Purifying, applied sample amount 10mL, flow velocity 1mL/min, every pipe collect 10mL, mobile phase be respectively pure water, 0.5mol/mLNaAc,
1.5mol/mLNaCl。
16. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 15, which is characterized in that described
Dialysis concentration is to be dialysed for 24 hours with the bag filter of molecular cut off 8KD-14KD in step S3.
17. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 16, which is characterized in that described
Freeze-drying is in 0.030~0.035kPa, -50~-55 DEG C of vacuum freezedrying 12-36h in step S3.
18. according to the preparation method of the described in any item pinctada fucata glycosaminoglycan effervescent tablets of claim 7,11,14,17,
It is characterized in that, in the step S4 screening to sieve with 100 mesh sieve, be granulated for 16 meshes, whole grain be 20 meshes.
19. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 18, which is characterized in that described
Drying is dried to moisture content lower than 0.5% in step S4 under the conditions of being 60-70 DEG C.
20. the preparation method of pinctada fucata glycosaminoglycan effervescent tablet according to claim 19, which is characterized in that described
Sterilizing is using ultraviolet disinfecting machine progress ultraviolet-sterilization in step S4.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2017111141859 | 2017-11-13 | ||
| CN201711114185 | 2017-11-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109588604A true CN109588604A (en) | 2019-04-09 |
Family
ID=65958476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811344841.9A Pending CN109588604A (en) | 2017-11-13 | 2018-11-13 | A kind of pinctada fucata glycosaminoglycan effervescent tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109588604A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1562073A (en) * | 2003-05-07 | 2005-01-12 | 汤毅 | Non-injection preparation containing medium and/or low molecular weight chondroitin sulfate |
| CN1947724A (en) * | 2006-03-10 | 2007-04-18 | 北京阜康仁生物制药科技有限公司 | Compound amino-glucose hydrochloride, chondroitin sulfate effervescent, tablets prepn. method and use thereof |
-
2018
- 2018-11-13 CN CN201811344841.9A patent/CN109588604A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1562073A (en) * | 2003-05-07 | 2005-01-12 | 汤毅 | Non-injection preparation containing medium and/or low molecular weight chondroitin sulfate |
| CN1947724A (en) * | 2006-03-10 | 2007-04-18 | 北京阜康仁生物制药科技有限公司 | Compound amino-glucose hydrochloride, chondroitin sulfate effervescent, tablets prepn. method and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| 周小双等: "响应面法优化合浦珠母贝糖胺聚糖提取工艺", 《食品与发酵工业》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102106502B (en) | Health-care food with functions of improving skin moisture and reinforcing immunity | |
| CN102077936B (en) | Special sea dietary food for diabetics | |
| RU2315487C1 (en) | Biologically active product from brown algae, biologically active food supplement, soft drink, perfume and cosmetic agent | |
| CN108853486B (en) | Formula product with function of enhancing immunity | |
| CN103876104A (en) | Prebiotic low-sodium salt and prebiotic low-sodium salt composite seasoning, and preparation method thereof | |
| CN102077939B (en) | Marine special dietary food special for fat people | |
| CN102077940B (en) | Special dietary marine food for patients with coronary heart disease | |
| CN102429235A (en) | Health care food with functions of relieving physical fatigue and enhancing immunity | |
| CN102077945B (en) | Special dietary seafood for postabortal and postpartum women | |
| CN102077937B (en) | Special dietary seafood special for young and middle-aged women | |
| WO2011047518A1 (en) | Enteral nutrition comprising marine bioactive polysaccharide, preparation method and use thereof | |
| CN101243824A (en) | Green pawpaw mastication tablet and producing method thereof | |
| CN102077942B (en) | Marine special dietary food special for patient with bone disease | |
| CN102823885A (en) | Sea cucumber chewable tablets and preparation method thereof | |
| CN102077938A (en) | Special marine dietary food for patients with liver deficiency | |
| CN107594533A (en) | A kind of pinctada fucata glycosaminoglycan chewable tablets and preparation method thereof | |
| CN102172288B (en) | Osteocalcin noodles and making method thereof | |
| CN105125606B (en) | Improve the chewable tablets and preparation method thereof of immunity | |
| CN103281914B (en) | Purification of soluble mannan compositions and using method thereof for dietary supplement | |
| CN103876141A (en) | Composition with effects of clearing away lung-heat and detoxifying and preparation method and application thereof | |
| CN101829158B (en) | Pig blood composition and pig blood chewable tablet made therefrom | |
| CN116898098A (en) | Boletus peptide anti-alcoholic formula and raw material preparation method | |
| CN102077943B (en) | Seafood for special dietary uses for hypomnesia patients | |
| CN109588604A (en) | A kind of pinctada fucata glycosaminoglycan effervescent tablet and preparation method thereof | |
| CN106107070A (en) | A kind of Chinese herbal medicine feed for goat and preparation method thereof |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190409 |