CN118048280A - Probiotic agent for improving spermatogenic disorder and application thereof - Google Patents
Probiotic agent for improving spermatogenic disorder and application thereof Download PDFInfo
- Publication number
- CN118048280A CN118048280A CN202410452391.4A CN202410452391A CN118048280A CN 118048280 A CN118048280 A CN 118048280A CN 202410452391 A CN202410452391 A CN 202410452391A CN 118048280 A CN118048280 A CN 118048280A
- Authority
- CN
- China
- Prior art keywords
- probiotic
- strain
- improving
- dysspermia
- bacillus coagulans
- 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
- 239000006041 probiotic Substances 0.000 title claims abstract description 54
- 235000018291 probiotics Nutrition 0.000 title claims abstract description 54
- 230000000529 probiotic effect Effects 0.000 title claims abstract description 39
- 239000003795 chemical substances by application Substances 0.000 title claims description 12
- 230000000920 spermatogeneic effect Effects 0.000 title claims description 10
- 241000186018 Bifidobacterium adolescentis Species 0.000 claims abstract description 16
- 241000193749 Bacillus coagulans Species 0.000 claims abstract description 15
- 230000021595 spermatogenesis Effects 0.000 claims abstract description 6
- 230000001580 bacterial effect Effects 0.000 claims description 16
- 239000000843 powder Substances 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 238000004321 preservation Methods 0.000 claims description 12
- 241000894006 Bacteria Species 0.000 claims description 8
- 206010003883 azoospermia Diseases 0.000 claims description 7
- 238000000855 fermentation Methods 0.000 claims description 6
- 230000004151 fermentation Effects 0.000 claims description 6
- 208000008634 oligospermia Diseases 0.000 claims description 6
- 230000036616 oligospermia Effects 0.000 claims description 6
- 231100000528 oligospermia Toxicity 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 4
- 239000012752 auxiliary agent Substances 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 4
- 239000001963 growth medium Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 241001495180 Arthrospira Species 0.000 claims description 2
- 240000002900 Arthrospira platensis Species 0.000 claims description 2
- 235000016425 Arthrospira platensis Nutrition 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 229920002307 Dextran Polymers 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 244000068988 Glycine max Species 0.000 claims description 2
- 235000010469 Glycine max Nutrition 0.000 claims description 2
- 229920001202 Inulin Polymers 0.000 claims description 2
- 102000004407 Lactalbumin Human genes 0.000 claims description 2
- 108090000942 Lactalbumin Proteins 0.000 claims description 2
- 102000010445 Lactoferrin Human genes 0.000 claims description 2
- 108010063045 Lactoferrin Proteins 0.000 claims description 2
- 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 claims description 2
- 240000007472 Leucaena leucocephala Species 0.000 claims description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 claims description 2
- 229920001100 Polydextrose Polymers 0.000 claims description 2
- UQZIYBXSHAGNOE-USOSMYMVSA-N Stachyose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO[C@@H]2[C@@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O2)O1 UQZIYBXSHAGNOE-USOSMYMVSA-N 0.000 claims description 2
- 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 description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 241000222355 Trametes versicolor Species 0.000 claims description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 239000000853 adhesive Substances 0.000 claims description 2
- 230000001070 adhesive effect Effects 0.000 claims description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 2
- 239000003963 antioxidant agent Substances 0.000 claims description 2
- 230000003078 antioxidant effect Effects 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 239000003086 colorant Substances 0.000 claims description 2
- 239000006184 cosolvent Substances 0.000 claims description 2
- HEBKCHPVOIAQTA-NGQZWQHPSA-N d-xylitol Chemical compound OC[C@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-NGQZWQHPSA-N 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 239000003995 emulsifying agent Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical compound OC[C@H]1O[C@@](CO)(OC[C@@]2(OC[C@@]3(OC[C@@]4(OC[C@@]5(OC[C@@]6(OC[C@@]7(OC[C@@]8(OC[C@@]9(OC[C@@]%10(OC[C@@]%11(O[C@H]%12O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%12O)O[C@H](CO)[C@@H](O)[C@@H]%11O)O[C@H](CO)[C@@H](O)[C@@H]%10O)O[C@H](CO)[C@@H](O)[C@@H]9O)O[C@H](CO)[C@@H](O)[C@@H]8O)O[C@H](CO)[C@@H](O)[C@@H]7O)O[C@H](CO)[C@@H](O)[C@@H]6O)O[C@H](CO)[C@@H](O)[C@@H]5O)O[C@H](CO)[C@@H](O)[C@@H]4O)O[C@H](CO)[C@@H](O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O FTSSQIKWUOOEGC-RULYVFMPSA-N 0.000 claims description 2
- 229940107187 fructooligosaccharide Drugs 0.000 claims description 2
- 235000021255 galacto-oligosaccharides Nutrition 0.000 claims description 2
- 150000003271 galactooligosaccharides Chemical class 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims description 2
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 claims description 2
- 229940029339 inulin Drugs 0.000 claims description 2
- DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 claims description 2
- 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 2
- 235000021242 lactoferrin Nutrition 0.000 claims description 2
- 229940078795 lactoferrin Drugs 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 229920001542 oligosaccharide Polymers 0.000 claims description 2
- 150000002482 oligosaccharides Chemical class 0.000 claims description 2
- 230000003204 osmotic effect Effects 0.000 claims description 2
- -1 pH regulator Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000001259 polydextrose Substances 0.000 claims description 2
- 235000013856 polydextrose Nutrition 0.000 claims description 2
- 229940035035 polydextrose Drugs 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 239000003223 protective agent Substances 0.000 claims description 2
- 235000020183 skimmed milk Nutrition 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 229940082787 spirulina Drugs 0.000 claims description 2
- UQZIYBXSHAGNOE-XNSRJBNMSA-N stachyose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)O2)O)O1 UQZIYBXSHAGNOE-XNSRJBNMSA-N 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- 235000021241 α-lactalbumin Nutrition 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 1
- 239000008176 lyophilized powder Substances 0.000 claims 1
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 abstract description 24
- 229960003604 testosterone Drugs 0.000 abstract description 12
- 210000002966 serum Anatomy 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 8
- 230000036542 oxidative stress Effects 0.000 abstract description 8
- 230000002829 reductive effect Effects 0.000 abstract description 6
- 230000002124 endocrine Effects 0.000 abstract description 5
- 230000028993 immune response Effects 0.000 abstract description 5
- 230000003993 interaction Effects 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 29
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 22
- 210000001550 testis Anatomy 0.000 description 12
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 11
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 11
- 102000013691 Interleukin-17 Human genes 0.000 description 9
- 108050003558 Interleukin-17 Proteins 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 9
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 8
- 229940118019 malondialdehyde Drugs 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000002381 testicular Effects 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000006872 mrs medium Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 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 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 235000015278 beef Nutrition 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 229960001305 cysteine hydrochloride Drugs 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 201000010063 epididymitis Diseases 0.000 description 2
- 229910052564 epsomite Inorganic materials 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000009027 insemination Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 230000003859 lipid peroxidation Effects 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 2
- 229910000357 manganese(II) sulfate Inorganic materials 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000009629 microbiological culture Methods 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 206010048554 Endothelial dysfunction Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- KLOIYEQEVSIOOO-UHFFFAOYSA-N carbocromen Chemical compound CC1=C(CCN(CC)CC)C(=O)OC2=CC(OCC(=O)OCC)=CC=C21 KLOIYEQEVSIOOO-UHFFFAOYSA-N 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 231100000507 endocrine disrupting Toxicity 0.000 description 1
- 230000008694 endothelial dysfunction Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 231100000317 environmental toxin Toxicity 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000007413 intestinal health Effects 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000008789 oxidative DNA damage Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000009933 reproductive health Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000019100 sperm motility Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention relates to a probiotic for improving spermatogenesis disorder and application thereof, wherein strains in the probiotic for improving spermatogenesis disorder comprise bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain and bacillus coagulans Bacillus coagulans BC strain. The invention develops a brand new probiotic compound mode, wherein a BAC30 strain and a BC99 strain are compounded, and potential interaction exists between the two strains, so that the two strains can be matched with each other, and the effects of improving dysspermia are synergistically enhanced, and the method is specifically characterized in that: the sperm density is effectively improved, and the deformity rate is reduced; significantly increasing serum testosterone levels; significantly reduces the oxidative stress of the organism, regulates the immune response and improves the endocrine balance.
Description
Technical Field
The invention belongs to the technical field of probiotics, and relates to a probiotic for improving dysspermia and application thereof.
Background
Seminiferous disorders involve a decrease in the number, quality and motor capacity of spermatogenesis, which is complicated by factors including genetic factors, environmental toxins, lifestyle, and certain diseases.
In recent years, probiotics are used as a biological agent for regulating the microecological balance of human bodies, and can improve intestinal health and enhance immunity. Specific species of probiotics can positively affect the improvement of spermatogenic function by regulating immune response, improving hormone level balance, reducing genital system inflammation and other mechanisms. While probiotics have demonstrated potential in improving dysspermia, there is currently a lack of probiotic formulations on the market specifically designed for dysspermia. Therefore, the novel and highly targeted probiotic agent is developed, so that not only can a novel treatment choice be provided for patients with dysspermia, but also a novel research direction is opened for the application of probiotics in the field of reproductive health.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a probiotic agent for improving spermatogenic disorder and application thereof, in particular to a probiotic agent for improving spermatogenic disorder and application thereof in preparing products for preventing, relieving or treating oligospermia or oligospermia.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
In a first aspect, the invention provides a probiotic for improving dysspermia, wherein the strains in the probiotic for improving dysspermia comprise bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain with the preservation number of CGMCC No.19884 and bacillus coagulans Bacillus coagulans BC strain with the preservation number of CGMCC No. 21801.
The invention develops a brand new probiotic compounding mode, and combines the bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain and the bacillus coagulans Bacillus coagulans BC strain, and finds that the bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain and the bacillus coagulans Bacillus coagulans BC strain have potential interaction, can be mutually matched, and synergistically improve the effect of improving the dysspermia, and is specifically characterized in that: (1) effectively improving sperm density and reducing deformity rate; (2) significantly increasing serum testosterone levels; (3) Significantly reduces the oxidative stress of the organism, regulates the immune response and improves the endocrine balance. When the amount of the bacteria used is uniform, the combination of the two bacteria significantly improves the efficacy as compared with the single BAC30 strain or the single BC99 strain. Thus, the probiotic provides a new strategy for improving insemination disorders. Since the bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain and the bacillus coagulans Bacillus coagulans BC strain are probiotics, the bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain and the bacillus coagulans Bacillus coagulans BC strain are high in safety and are not easy to generate resistance when being used for preparing products with related effects.
Preferably, the ratio of the viable count of the bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain to that of the bacillus coagulans Bacillus coagulans BC strain is 1:20-20:1, for example 1:20、1:18、1:16、1:15、1:12、1:10、1:9、1:8、1:7、1:6、1:5、1:4、1:3、1:2、1:1、2:1、3:1、4:1、5:1、6:1、7:1、8:1、9:1、10:1、12:1、15:1、18:1、20:1, and other specific values within the above numerical range can be selected, and will not be described in detail herein.
Based on the potential interaction relationship between the BAC30 strain and the BC99 strain, the invention also discovers that when the two strains are compounded according to the specific viable count ratio, the effects of improving sperm density, reducing deformity rate, improving serum testosterone level, relieving oxidative stress of an organism, regulating immune response and improving endocrine balance are more remarkable.
Preferably, in the probiotic agent, the total number of viable bacteria is not lower than 2×10 9 CFU/mL or 2×10 9 CFU/g, such as 2×109 CFU/mL（CFU/g）、5×109 CFU/mL（CFU/g）、1×1010 CFU/mL（CFU/g）、5×1010 CFU/mL（CFU/g）、1×1011 CFU/mL（CFU/g）、1×1012 CFU/mL（CFU/g）、1×1013 CFU/mL（CFU/g）, etc.; other specific point values within the numerical range can be selected, and will not be described in detail herein.
Preferably, the formulation of the probiotic agent comprises freeze-dried powder, capsules, tablets or granules.
The formulation of the probiotics related to the invention is not limited, and comprises the most commonly used freeze-dried powder, or further prepared capsules, tablets or granules.
Preferably, the probiotic agent further comprises a lyoprotectant and/or a functional adjuvant.
Preferably, the lyoprotectant comprises any one or a combination of at least two of skim milk, gelatin, dextrin, acacia, dextran, sodium alginate, polyvinylpyrrolidone, sucrose, lactose, trehalose, sorbitol or xylitol.
The functional auxiliary agent comprises any one or a combination of at least two of fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, isomalto-oligosaccharide, soybean oligosaccharide, inulin, spirulina, arthrospira, coriolus versicolor polysaccharide, stachyose, polydextrose, alpha-lactalbumin or lactoferrin.
Preferably, the probiotic is prepared by a preparation method comprising:
Respectively inoculating BAC30 strain and BC99 strain into a culture medium for activation and fermentation culture to obtain fermentation liquor; respectively centrifuging the fermentation liquid, mixing with a freeze-drying protective agent, and freeze-drying to obtain BAC30 bacterial powder and BC99 bacterial powder; and mixing BAC30 bacterial powder and BC99 bacterial powder according to the ratio of the viable count to obtain the probiotic agent for improving the spermatogenesis disorder.
Preferably, the medium includes an MRS medium.
Preferably, the MRS medium includes, in concentration: 8-12 g/L of peptone, 8-12 g/L of beef extract, 15-25 g/L of glucose, 1-3 g/L of sodium acetate, 3-7 g/L of yeast powder, 1-3 g/L、K2PO4·3H2O 2-3 g/L、MgSO4·7H2O 0.05-0.2 g/L、MnSO4 0.01-0.1 g/L、 Tween 80 0.5-2 mL/L of diammonium hydrogen citrate and 0.1-1 g/L of cysteine hydrochloride.
Preferably, the BAC30 bacterial powder and the BC99 bacterial powder are mixed according to the viable count ratio and then are mixed with the functional auxiliary agent.
In a second aspect, the present invention provides the use of a probiotic according to the first aspect for the preparation of a product for preventing, alleviating or treating oligospermia or oligospermia.
Preferably, the product further comprises auxiliary materials.
The auxiliary materials comprise any one or a combination of at least two of excipient, filler, adhesive, wetting agent, disintegrating agent, emulsifying agent, cosolvent, solubilizer, osmotic pressure regulator, coating material, colorant, pH regulator, antioxidant, bacteriostat or buffer.
Compared with the prior art, the invention has the following beneficial effects:
The invention develops a brand new probiotic compounding mode, and combines the bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain and the bacillus coagulans Bacillus coagulans BC strain, and finds that the bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain and the bacillus coagulans Bacillus coagulans BC strain have potential interaction, can be mutually matched, and synergistically improve the effect of improving the dysspermia, and is specifically characterized in that: (1) effectively improving sperm density and reducing deformity rate; (2) significantly increasing serum testosterone levels; (3) Significantly reduces the oxidative stress of the organism, regulates the immune response and improves the endocrine balance. When the amount of the bacteria used is uniform, the combination of the two bacteria significantly improves the efficacy as compared with the single BAC30 strain or the single BC99 strain. Thus, the probiotic provides a new strategy for improving insemination disorders. Since the bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain and the bacillus coagulans Bacillus coagulans BC strain are probiotics, the bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain and the bacillus coagulans Bacillus coagulans BC strain are high in safety and are not easy to generate resistance when being used for preparing products with related effects.
The BAC30 strain related to the invention is classified and named as bifidobacterium adolescentis Bifidobacterium adolescentis, the preservation unit is China general microbiological culture Collection center, the preservation time is 05 months and 28 days in 2020, the preservation number is CGMCC No.19884, and the address is: the korean district North Star, beijing city, part No.1, no. 3.
The BC99 strain related by the invention is classified and named as bacillus coagulans Bacillus coagulans, the preservation unit is China general microbiological culture Collection center, the preservation time is 2021, 02 and 01, the preservation number is CGMCC No.21801, and the address is: the korean district North Star, beijing city, part No. 1, no. 3.
Drawings
FIG. 1 is a graph of the statistics of sperm density for each group of mice;
FIG. 2 is a graph of statistical results of sperm cell abnormal rates for each group of mice;
FIG. 3 is a graph of statistical results of serum testosterone levels for each group of mice;
FIG. 4 is a graph of statistical results of Lactate Dehydrogenase (LDH) levels in testis tissue of each group of mice;
FIG. 5 is a graph of statistical results of Malondialdehyde (MDA) levels in testis tissue of various groups of mice;
FIG. 6 is a graph of statistical results of Nitric Oxide (NO) levels in testis tissue of each group of mice;
FIG. 7 is a graph of statistical results of interleukin-17 (IL-17) levels in testis tissue of each group of mice;
FIG. 8 is a graph of statistical results of tumor necrosis factor-alpha (TNF-alpha) levels in testis tissue of each group of mice.
Detailed Description
The technical scheme of the invention is further described by the following specific embodiments. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the invention and are not to be construed as a specific limitation thereof.
The medium formulations referred to in the examples below were as follows:
MRS Medium (g/L): 10g/L of peptone, 10g/L of beef extract, 20g/L of glucose, 2g/L of sodium acetate, 5g/L of yeast powder, 1ml/L of 2g/L、K2PO4·3H2O 2.6g/L、MgSO4·7H2O 0.1g/L、MnSO4 0.05g/L、 Tween 80 and 0.5g/L of cysteine hydrochloride.
The BAC30 strain related to the following examples is classified and named as bifidobacterium adolescentis Bifidobacterium adolescentis, and the preservation number is CGMCC No.19884.
The BC99 strain related to the following embodiment is classified and named as bacillus coagulans Bacillus coagulans, and the preservation number is CGMCC No.21801.
The preparation method of the bacterial suspension comprises the following steps: inoculating the required strain into MRS liquid culture medium, culturing at 37deg.C for 18h for activation, and continuously activating for 2 times to obtain activating solution; inoculating the activating solution into MRS liquid culture medium according to the inoculum size of 2% (v/v), and culturing at 37 ℃ for 24h to obtain bacterial solution; centrifuging the bacterial liquid at 5000rpm at 4deg.C for 10 min, filtering to obtain bacterial cells, and re-suspending bacterial cells with PBS solution.
Statistical analysis of experimental results data using ggplot of R language, # represents p <0.001, # represents p <0.01, # represents p <0.05, compared to CTL group; compared to the MC group, p <0.001, p <0.01, p <0.05, ns represents no significant difference.
Examples
This example explores the ability of probiotics to improve symptoms in dysspermia mice:
(1) Test animals: SPF class C57BL/6 male mice (purchased from Shanghai laboratory animal center) 6 weeks old were kept in cages with clean and quiet environment, 20-24℃and 50-60% humidity, following 12h light/dark cycle. All experimental procedures involving mice were in compliance with the ethical guidelines for animal care and use prescribed by the Shanghai laboratory animal Care and animal Experimental center.
(2) Grouping animals: after 1 week of adaptive feeding in the above mice, 56 mice were randomly divided into 7 groups (8 per group): control group (CTL group), model group (MC group), BAC30 strain-interfered mice group (BAC 30 group, designated as S1 group), BC99 strain-interfered mice group (BC 99 group, designated as S2 group), commercial bifidobacterium adolescentis strain ATCC 15703-interfered mice group (ATCC 15703 group, designated as S3 group), BAC30 strain-BC 99 strain-combined interfered mice group (bac30+bc 99 group, 1:1 ratio of the number of live bacteria of both strains, designated as S4 group), BC99 strain-combined interfered mice group (ATCC 15703+bc 99 group, 1:1 ratio of the number of live bacteria of both strains, designated as S5 group).
(3) Animal modeling and intervention method: except for the control group, all groups of mice received busulfan (35 mg/kg) intraperitoneal injection to establish a azoospermia mouse model. After 30 days, the CTL group and the MC group are infused with normal saline for 1 time a day for 5 weeks; each probiotic group was treated with different bacterial solutions (1 x 10 10 CFU/dose) at a frequency of 1 time per day for 5 consecutive weeks (35 days of mice seminiferous cycle).
(4) And (3) index analysis:
(4.1) mouse sperm quality detection:
Mice were anesthetized by intraperitoneal injection of 0.3% sodium pentobarbital, and immediately after anesthesia, the left epididymal tail was removed, a semen sample was obtained from the epididymal tail of the mice, and transferred to the medium. The samples were then incubated in a 37 ℃ water bath for 15 min to release sperm. The samples were then filtered and diluted with additional 0.5 mL normal saline, 20 μl of the diluted droplets were applied to a slide, and the samples were analyzed using a semen analyzer to evaluate sperm density and morphology. For sperm count (density), 0.5 mL of the filtered and diluted sperm suspension was placed in a 10 mL EP tube, 0.5 mL of 0.5% NaHCO 3 fixative was added, and after blowing evenly, 20 μl of diluted droplets were counted on a blood cell counting plate.
The statistics of sperm density and sperm malformation rate of each group are shown in fig. 1 and 2, respectively. From the figure, the sperm density of mice in the model group is obviously reduced compared with that of mice in the control group, which indicates that the model establishment successfully induces the damage of the spermatogenic function, has negative effect on the growth and division of spermatids in testes, and leads to reduced spermatogenesis; sperm cell deformity increases significantly, which may be associated with oxidative stress, DNA damage, or endocrine disruption during modeling, which can significantly affect sperm motility and fertility. After each group of probiotics intervenes, especially in the S4 group, the situation is obviously reversed, so that the sperm density is obviously increased and the deformity rate is obviously reduced, and the changes are helpful to restore the normal spermatogenic process and sperm development, thereby improving the number and quality of sperms.
(4.2) Serum testosterone (T) level detection: the serum testosterone (T) levels of each group of mice were detected using enzyme-linked immunosorbent assay (ELISA) technology using a scientific kit provided by Wohan purity Biotechnology Co.
The statistical results of serum testosterone (T) levels for each group are shown in figure 3. From the figure, testosterone levels were significantly reduced in mice in the model group compared to the control group, indicating that model establishment successfully mimics the state of reproductive endocrine dysfunction. After each group of probiotics was intervened, especially in S4 group, serum testosterone levels were significantly increased, indicating the potential effect of probiotics on improving testicular function and promoting testosterone synthesis.
(4.3) Biochemical test of testis:
Mouse testis tissue was taken and examined the day after homogenization, avoiding repeated freeze thawing to reduce enzyme activity. Specifically, a proper amount of physiological saline (with the concentration of 0.9% and the temperature of about 4 ℃) is taken, the mixture is put into testis tissue of a mouse, 10% tissue homogenate is prepared under the ice water bath condition, the homogenate is placed into a centrifugal machine, the centrifugal machine is used for centrifugation at the rotating speed of 3000r/min for 10min, and the supernatant is carefully taken out in a test tube to obtain the tissue homogenate. The level of Lactate Dehydrogenase (LDH), malondialdehyde (MDA), nitric Oxide (NO), interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-alpha) in testis tissue was detected according to the procedure shown in the specification using a scientific kit provided by Wohan purity Biotechnology Co.
Statistical results of Lactate Dehydrogenase (LDH), malondialdehyde (MDA), nitric Oxide (NO), interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-alpha) levels in testis tissue of each group of mice are shown in FIGS. 4-8, respectively.
From the figure, the levels of testosterone, nitric oxide, interleukin-17 and tumor necrosis factor-alpha were significantly increased in the mice in the model group and the lactate dehydrogenase level was significantly decreased in the model group compared to the control group. Malondialdehyde is the end product of lipid peroxidation, and its elevated levels indicate a significant oxidative stress in the model group, affecting cell function and structure, and thus damaging testicular tissue. Nitric oxide is an important biological signaling molecule, but its overproduction may lead to inflammation and cellular injury, and elevated nitric oxide levels in the model set may reflect inflammatory states and endothelial dysfunction. Interleukin-17 and tumor necrosis factor- α are key pro-inflammatory cytokines in the inflammatory process, and elevated levels of these two cytokines indicate a significant inflammatory response in testis tissue in mice in the model group. Lactate dehydrogenase is a marker of cell damage and cell death, and a decrease in lactate dehydrogenase levels in the model set may reflect a decrease in cellular metabolic activity or impairment of cellular integrity.
After each group of probiotic interventions, especially in the S4 group, levels of testicular malondialdehyde, nitric oxide, interleukin-17 and tumor necrosis factor- α were significantly reduced and lactate dehydrogenase levels were significantly increased. This shows that the probiotic intervention according to the invention is effective in reducing the oxidative stress and inflammatory states of testicular tissue. Probiotic intervention helps to protect testicular tissue from further damage by reducing lipid peroxidation products, modulating nitric oxide production, and inhibiting the release of pro-inflammatory cytokines. The increase in lactate dehydrogenase levels may reflect a restoration of cellular metabolic activity and an improvement in cellular integrity following probiotic intervention, possibly due to the reduction of oxidative stress and inflammation by the probiotics, thereby promoting restoration of cell repair and function.
The applicant states that the technical solution of the present invention is illustrated by the above embodiments, but the present invention is not limited to the above embodiments, i.e. it does not mean that the present invention must be implemented by the above embodiments. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.
In addition, the specific features described in the above embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, various possible combinations are not described further.
Claims (10)
1. The probiotics for improving the spermatogenic disorder is characterized in that strains in the probiotics for improving the spermatogenic disorder comprise a bifidobacterium adolescentis Bifidobacterium adolescentisBAC strain with a preservation number of CGMCC No.19884 and a bacillus coagulans Bacillus coagulans BC99 strain with a preservation number of CGMCC No. 21801.
2. The probiotic for improving dysspermia according to claim 1, characterized in that the ratio of viable count of bifidobacterium adolescentis Bifidobacterium adolescentis BAC strain to bacillus coagulans Bacillus coagulans BC strain is 1:20-20:1.
3. The probiotic for improving dysspermia according to claim 1, characterized in that in the probiotic the total number of viable bacteria is not lower than 2 x 10 9 CFU/mL or 2 x 10 9 CFU/g.
4. The probiotic for ameliorating dysspermia according to claim 1, wherein the probiotic is in a dosage form comprising a lyophilized powder, capsule, tablet or granule.
5. A probiotic for ameliorating dysspermia according to claim 1, wherein said probiotic further comprises lyoprotectants and/or functional adjuvants.
6. The probiotic for ameliorating dysspermia according to claim 5, wherein the lyoprotectant comprises any one or a combination of at least two of skim milk, gelatin, dextrin, acacia, dextran, sodium alginate, polyvinylpyrrolidone, sucrose, lactose, trehalose, sorbitol or xylitol;
The functional auxiliary agent comprises any one or a combination of at least two of fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, isomalto-oligosaccharide, soybean oligosaccharide, inulin, spirulina, arthrospira, coriolus versicolor polysaccharide, stachyose, polydextrose, alpha-lactalbumin or lactoferrin.
7. The probiotic for improving dysspermia according to claim 1, characterized in that it is prepared by a preparation process comprising:
Respectively inoculating BAC30 strain and BC99 strain into a culture medium for activation and fermentation culture to obtain fermentation liquor; respectively centrifuging the fermentation liquid, mixing with a freeze-drying protective agent, and freeze-drying to obtain BAC30 bacterial powder and BC99 bacterial powder; and mixing BAC30 bacterial powder and BC99 bacterial powder according to the ratio of the viable count to obtain the probiotic agent for improving the spermatogenesis disorder.
8. The probiotic for improving dysspermia according to claim 7, wherein BAC30 powder and BC99 powder are mixed according to the ratio of viable count and then mixed with functional auxiliary agent.
9. Use of a probiotic for ameliorating a spermatogenic disorder according to any of claims 1-8 in the manufacture of a product for preventing, alleviating or treating oligospermia or oligospermia.
10. The use according to claim 9, wherein the product further comprises adjuvants;
the auxiliary materials comprise any one or a combination of at least two of excipient, filler, adhesive, wetting agent, disintegrating agent, emulsifying agent, cosolvent, solubilizer, osmotic pressure regulator, coating material, colorant, pH regulator, antioxidant, bacteriostat or buffer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410452391.4A CN118048280B (en) | 2024-04-16 | 2024-04-16 | Probiotic agent for improving spermatogenic disorder and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410452391.4A CN118048280B (en) | 2024-04-16 | 2024-04-16 | Probiotic agent for improving spermatogenic disorder and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN118048280A true CN118048280A (en) | 2024-05-17 |
| CN118048280B CN118048280B (en) | 2024-06-14 |
Family
ID=91050404
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410452391.4A Active CN118048280B (en) | 2024-04-16 | 2024-04-16 | Probiotic agent for improving spermatogenic disorder and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118048280B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112852679A (en) * | 2021-03-17 | 2021-05-28 | 武汉微康益生菌研究院有限公司 | Probiotic bacillus coagulans and application thereof |
| CN114774318A (en) * | 2022-04-19 | 2022-07-22 | 微康益生菌(苏州)股份有限公司 | Application of lactobacillus paracasei in preparation of product for relieving anxiety and depression symptoms |
-
2024
- 2024-04-16 CN CN202410452391.4A patent/CN118048280B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112852679A (en) * | 2021-03-17 | 2021-05-28 | 武汉微康益生菌研究院有限公司 | Probiotic bacillus coagulans and application thereof |
| CN114774318A (en) * | 2022-04-19 | 2022-07-22 | 微康益生菌(苏州)股份有限公司 | Application of lactobacillus paracasei in preparation of product for relieving anxiety and depression symptoms |
Also Published As
| Publication number | Publication date |
|---|---|
| CN118048280B (en) | 2024-06-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20190216866A1 (en) | Composite probiotic lactic acid bacteria powder and preparation method and use thereof | |
| CN113430133A (en) | Composite probiotics capable of relieving ulcerative colitis, preparation method and application thereof | |
| CN109022317B (en) | Preparation method of clostridium butyricum powder | |
| CN117070426B (en) | Probiotic agent for improving alcoholic fatty liver disease and application thereof | |
| CN111480849B (en) | Composite probiotic microcapsule powder for mother emulsification and preparation method and application thereof | |
| CN115216422B (en) | Lactobacillus rhamnosus and application thereof | |
| CN117778279B (en) | Probiotic agent for degrading ethanol and application thereof | |
| CN117106679A (en) | Probiotic agent for relieving insulin resistance and application thereof | |
| CN117286077B (en) | Probiotics for preventing and treating acute radioactive intestinal injury and application thereof | |
| CN113881597A (en) | Lactobacillus reuteri capable of improving indoleacrylic acid to regulate specific IgE | |
| CN118048280B (en) | Probiotic agent for improving spermatogenic disorder and application thereof | |
| CN116694509A (en) | Lactobacillus plantarum for metabolizing L-tryptophan to produce indole derivatives and having intestinal barrier function enhancing function and application thereof | |
| CN112546074B (en) | Bifidobacterium breve capable of inhibiting release of IL-23 and Th17 axis-related inflammatory factors and application thereof | |
| CN117778275B (en) | Probiotic agent for improving oligospermia and application thereof | |
| CN113186118B (en) | Composite probiotic preparation for improving sow productivity and preparation method thereof | |
| CN115418332A (en) | Lactobacillus plantarum capable of preventing and improving chemical liver injury | |
| CN111700918B (en) | Medicine for relieving alcoholic intestinal injury | |
| CN113913330A (en) | Lactobacillus plantarum for regulating OVA (ovalbumin oxidase) specificity IgE and application thereof | |
| CN118086152B (en) | Composite probiotics for improving bacterial vaginitis, probiotics preparation and application thereof | |
| CN117821343B (en) | Composite probiotics for regulating blood glucose metabolism and application thereof | |
| CN117959343B (en) | Probiotic agent for improving viral pneumonia and application thereof | |
| CN118086154B (en) | Probiotic agent for improving chronic low-grade inflammation and application thereof | |
| CN117987327B (en) | Compound probiotics for resisting hepatitis B virus and application thereof | |
| CN118147021B (en) | Composite probiotics for relieving gouty arthritis and application thereof | |
| CN116606761B (en) | Bifidobacterium animalis subspecies BLa19 capable of relieving rheumatoid arthritis and application 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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |