JP2018035084A - Skin antimicrobial composition - Google Patents
Skin antimicrobial composition Download PDFInfo
- Publication number
- JP2018035084A JP2018035084A JP2016168572A JP2016168572A JP2018035084A JP 2018035084 A JP2018035084 A JP 2018035084A JP 2016168572 A JP2016168572 A JP 2016168572A JP 2016168572 A JP2016168572 A JP 2016168572A JP 2018035084 A JP2018035084 A JP 2018035084A
- Authority
- JP
- Japan
- Prior art keywords
- skin
- molecular weight
- lps
- measured
- antimicrobial composition
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 7
- 230000000845 anti-microbial effect Effects 0.000 title claims abstract 4
- 239000002158 endotoxin Substances 0.000 claims abstract description 11
- 229920006008 lipopolysaccharide Polymers 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 11
- 241000520272 Pantoea Species 0.000 claims abstract description 5
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 claims abstract description 3
- 230000000813 microbial effect Effects 0.000 claims abstract 4
- 239000004480 active ingredient Substances 0.000 claims abstract 2
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 claims description 4
- 230000000844 anti-bacterial effect Effects 0.000 claims description 3
- 108090000623 proteins and genes Proteins 0.000 claims description 3
- MSWZFWKMSRAUBD-UHFFFAOYSA-N 2-Amino-2-Deoxy-Hexose Chemical compound NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 2
- KYQCXUMVJGMDNG-UHFFFAOYSA-N 4,5,6,7,8-pentahydroxy-2-oxooctanoic acid Chemical compound OCC(O)C(O)C(O)C(O)CC(=O)C(O)=O KYQCXUMVJGMDNG-UHFFFAOYSA-N 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 210000002510 keratinocyte Anatomy 0.000 abstract description 12
- 210000004027 cell Anatomy 0.000 abstract description 11
- 210000003491 skin Anatomy 0.000 abstract description 10
- 108010034929 Dermcidin Proteins 0.000 abstract description 3
- 210000004920 epithelial cell of skin Anatomy 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 210000000106 sweat gland Anatomy 0.000 abstract description 3
- 210000004243 sweat Anatomy 0.000 abstract description 2
- 102000030805 Dermcidin Human genes 0.000 abstract 2
- 230000001939 inductive effect Effects 0.000 abstract 1
- 239000012474 protein marker Substances 0.000 abstract 1
- 150000003384 small molecules Chemical class 0.000 abstract 1
- 241000588724 Escherichia coli Species 0.000 description 5
- 238000010804 cDNA synthesis Methods 0.000 description 4
- 108020004635 Complementary DNA Proteins 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102100026992 Dermcidin Human genes 0.000 description 2
- 239000012614 Q-Sepharose Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108091092584 GDNA Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000239218 Limulus Species 0.000 description 1
- 241000588912 Pantoea agglomerans Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 102000055135 Vasoactive Intestinal Peptide Human genes 0.000 description 1
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
この発明は、特定の理化学的性質を有し、安全性が極めて高く、かつ生物活性の高い低分子量リポポリサッカライド(LMM-LPS)を配合してなる皮膚用抗菌組成物に関するものである。 The present invention relates to an antibacterial composition for skin comprising specific low physicochemical properties, extremely high safety and high biological activity and low molecular weight lipopolysaccharide (LMM-LPS).
ダームシジンは汗腺で産生し汗に含まれることが知られており、皮膚の抗菌作用に重要な働きを持つとされる。そこで、我々は、皮膚全体を覆うのは皮膚上皮細胞のケラチノサイトであることから、この細胞からダームシジンが誘導出来る物質を開発することができれば、汎用性が高く、常に皮膚の健康状態を維持出来ると考えた。 Darmcidin is known to be produced in sweat glands and contained in sweat, and has an important role in the antibacterial action of the skin. Therefore, since we cover the entire skin with keratinocytes of skin epithelial cells, if we can develop a substance that can induce dermiscidin from these cells, it is highly versatile and always maintains the health of the skin. Thought.
しかしながら、ケラチノサイトからダームシジンは産生しないことが報告されている。さらに、文献ではLPSでも誘導しないことが記載されている（非特許文献１）。 However, it has been reported that no dermiscidin is produced from keratinocytes. Furthermore, the literature describes that LPS does not induce (Non-patent Document 1).
ケラチノサイトからダームシジンを産生する課題について、我々は鋭意研究したところ、パントエア菌LPSから得られる分子量5000±2000の低分子量LPS (LMM-LPS)は、これまでの常識を覆してケラチノサイトからダームシジンを産生することを見出し、本発明を確立することが出来た。 As a result of intensive research on the problem of producing dermatidin from keratinocytes, the low molecular weight LPS (LMM-LPS) with a molecular weight of 5000 ± 2000 obtained from Pantoea LPS produces dermsidin from keratinocytes. As a result, the present invention has been established.
皮膚全体を覆う皮膚上皮細胞のケラチノサイトからダームシジンが誘導出来る物質を開発したので、汎用性が高く、常に皮膚の健康状態を維持出来る。 Since a substance that can induce dermiscidin from keratinocytes of skin epithelial cells that cover the entire skin has been developed, it is highly versatile and can always maintain the health of the skin.
低分子量リポポリサッカライドがケラチノサイトからダームシジンを産生することを明らかにするために、ケラチノサイトから誘導されるメッセンジャーRNA (mRNA)を比較定量するリアルタイムPCR法を用いた。 In order to clarify that low molecular weight lipopolysaccharide produces dermisidin from keratinocytes, a real-time PCR method was used to compare and quantify messenger RNA (mRNA) derived from keratinocytes.
本発明に使用した低分子量リポポリサッカライドは、パントエア・アグロメランスを常法により培養し、培地から菌体を集め、集めた菌体から公知の方法、例えば、熱フェノール法［オー・ウエストファール（O．Westphal）編、メソッズ・イン・カーボハイドレート・ケミストリー（Methods in Carbohydrate Chemistry）、第５巻、第８３ページ、アカデミック・プレス（Academic Press）１９６５年］、により抽出し、さらに、陰イオン交換樹脂により精製して製造した。すなわち、パントエア菌の菌体を蒸留水に懸濁し、この懸濁液を蒸留水および等容量の熱フェノールの混合液に添加して撹拌し、次いで遠心分離して水層を回収し、この水層を透析してフェノールを除去し、限界濾過法により濃縮して粗ＬＰＳ画分を採取し、この画分を常法の陰イオン交換クロマトグラフィー（例えば、モノＱ−セファロースまたはＱ−セファロースを使用する）により精製し常法により脱塩して、精製LPSを得た。 The low-molecular-weight lipopolysaccharide used in the present invention is obtained by culturing pantoea agglomerans according to a conventional method, collecting bacterial cells from the medium, and collecting the collected bacterial cells by a known method such as the hot phenol method [O Westfale (O Westphal), Methods in Carbohydrate Chemistry, Volume 5, page 83, Academic Press 1965], and anion exchange resin And purified. That is, the cells of Pantoea are suspended in distilled water, the suspension is added to a mixture of distilled water and an equal volume of hot phenol and stirred, and then centrifuged to recover the aqueous layer. The layer is dialyzed to remove phenol and concentrated by ultrafiltration to obtain a crude LPS fraction, which is collected using conventional anion exchange chromatography (eg, using mono-Q-sepharose or Q-sepharose). And desalted by a conventional method to obtain purified LPS.
得られた精製LPSは既報（特許文献１）に従い、デオキシコール酸ナトリウム等の界面活性剤の存在下でゲル濾過し、低分子量ＬＳＰを含有する画分のみを回収し、混在する高分子量ＬＳＰを除去することによって、高度に精製された低分子量リポポリサッカライドを得た(LMM-LPS)。 Purified LPS obtained was gel filtered in the presence of a surfactant such as sodium deoxycholate according to a report (Patent Document 1), and only the fraction containing low molecular weight LSP was recovered. Removal gave a highly purified low molecular weight lipopolysaccharide (LMM-LPS).
以上の方法により製造されたこの発明の新規な低分子量ＬＰＳは、
ａ）タンパク質マーカーを用いてＳＤＳ−ＰＡＧＥ法で測定した分子量が５，０００±２，０００であり
ｂ）エルソン−モルガン法により測定したヘキソサミン含量が１〜３個／分子量５，０００であること
ｃ）ジフェニルアミン法により測定した２−ケト−３−デオキシオクトネート含量が１〜３個／分子量５，０００であること
ｄ）リムラス活性が、少なくとも１０ＥＵ／ｎｇであること
ｅ）タンパク質含量が、１％以下であること
ｆ）核酸含量が、１％以下であること
という理化学的および生物学的性質を有し、かつ少なくとも９８％の純度を有している。
The novel low molecular weight LPS of the present invention produced by the above method is
a) The molecular weight measured by SDS-PAGE using protein markers is 5,000 ± 2,000 b) The hexosamine content measured by Elson-Morgan method is 1 to 3 / molecular weight 5,000 c ) The content of 2-keto-3-deoxyoctonate measured by the diphenylamine method is 1 to 3 / molecular weight 5,000 d) The limulus activity is at least 10 EU / ng e) The protein content is 1% F) It has physicochemical and biological properties that the nucleic acid content is 1% or less and has a purity of at least 98%.
ケラチノサイトとしては、正常ヒト単離のケラチノサイトと同等の性質を示すDMJ-1細胞（非特許文献２）を理研バイオリソースセンターから購入した。DJM-1細胞は、培養液（10% FBS、100U/mLペニシリン、100μg/mLストレプトマイシンを含有するMEM培地）にて継代培養したものを用いた。 As keratinocytes, DMJ-1 cells (Non-patent Document 2) exhibiting the same properties as keratinocytes isolated from normal humans were purchased from the RIKEN BioResource Center. The DJM-1 cells used were subcultured in a culture solution (MEM medium containing 10% FBS, 100 U / mL penicillin, 100 μg / mL streptomycin).
Escherichia coli LPSは、SIMA ALDRICHから購入したEscherichia coli 0111:B4株由来のもの（製品番号L2630-10MG）を用いた。 As Escherichia coli LPS, one derived from Escherichia coli 0111: B4 purchased from SIMA ALDRICH (product number L2630-10MG) was used.
DJM-1細胞1×106 cellを直径6cmのプラスチックディッシュに播種し、37℃の5％炭酸ガスインキュベーターで24時間培養した。24時間後に培養液を除き、LPSを含む培養液に交換し、6時間培養を行った、培養後、リン酸緩衝液でディッシュを洗浄後、RNA抽出バッファーを加え、細胞を懸濁した。細胞懸濁液を1.5mLチューブに移し、RNeasy mini kit（キアゲン）を用いて全RNAを調整した。 DJM-1 cells 1 × 10 6 cells were seeded on a plastic dish having a diameter of 6 cm and cultured in a 5% carbon dioxide incubator at 37 ° C. for 24 hours. After 24 hours, the culture solution was removed and replaced with a culture solution containing LPS and cultured for 6 hours. After culturing, the dish was washed with a phosphate buffer, and then an RNA extraction buffer was added to suspend the cells. The cell suspension was transferred to a 1.5 mL tube, and total RNA was prepared using RNeasy mini kit (Qiagen).
抽出した全RNAに含まれるmRNAを増幅するための準備段階として、相補的DNA(cDNA)を合成した。cDNA合成にはReverTra Ace(R) qPCR RT Master Mix with gDNA Remover（TOYOBO）を用いた。合成した相補的DNAを鋳型にして、定量ポリメラーゼチェインリアクション(PCR)を実施した。定量PCRはサイバーグリーン（iQ(TM) SYBR(R) Green スーパーミックス（バイオラッド)）を用いて行った。ダームシジン（DCD、アクセッション番号NM_053283）遺伝子の発現量はβ-actinを標準としてΔΔCT法を用いて算出した。 As a preparatory step for amplifying mRNA contained in the extracted total RNA, complementary DNA (cDNA) was synthesized. ReverTra Ace® qPCR RT Master Mix with gDNA Remover (TOYOBO) was used for cDNA synthesis. Quantitative polymerase chain reaction (PCR) was performed using the synthesized complementary DNA as a template. Quantitative PCR was performed using Cyber Green (iQ (TM) SYBR (R) Green Supermix (Bio-Rad)). The expression level of the damcidin (DCD, accession number NM_053283) gene was calculated using the ΔΔCT method with β-actin as a standard.
結果
ヒトケラチノサイト細胞のDJM-1細胞を大腸菌LPS（LPSe）、パントエア菌由来の低分子量LPS(LMM-LPS)）で刺激した６時間後の結果を図１に示した。大腸菌LPSは一般的に使用されている高分子量を多く含むLPSとして用いた。図１に示されるように、10ng/mlの大腸菌LPSではダームシジンの誘導はほとんど起こらなかったが、LMM-LPSはダームシジンを誘導していた。
Results The results after 6 hours of stimulating human keratinocyte cells DJM-1 cells with Escherichia coli LPS (LPSe), Pantoea-derived low molecular weight LPS (LMM-LPS)) are shown in FIG. E. coli LPS was used as a LPS containing a large amount of high molecular weight that is generally used. As shown in FIG. 1, 10 ng / ml E. coli LPS hardly induced dermiscidin, but LMM-LPS induced dermiscidin.
以上のことから、低分子量LPSはヒトケラチノサイトからダームシジンを誘導することを明らかにした。
From the above, it was clarified that low molecular weight LPS induces darmsidin from human keratinocytes.
Claims (2)
ａ）タンパク質マーカーを用いてＳＤＳ−ＰＡＧＥ法で測定した分子量が５，０００±２，０００であり
ｂ）エルソン−モルガン法により測定したヘキソサミン含量が１〜３個／分子量５，０００であること
ｃ）ジフェニルアミン法により測定した２−ケト−３−デオキシオクトネート含量が１〜３個／分子量５，０００であること
を有する低分子量リポポリサッカライドを有効成分として含有することを特徴とする皮膚用抗菌組成物。 The following physicochemical properties a) to c) obtained from microbial cells: a) molecular weight measured by SDS-PAGE using protein markers is 5,000 ± 2,000 b) by Elson-Morgan method The measured hexosamine content is 1 to 3 / molecular weight 5,000 c) the low 2-keto-3-deoxyoctonate content measured by the diphenylamine method is 1 to 3 / molecular weight 5,000 An antibacterial composition for skin, comprising a molecular weight lipopolysaccharide as an active ingredient.
The antimicrobial composition for skin according to claim 1, wherein the microbial cell is a microbial cell belonging to the genus Pantoea.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016168572A JP6995468B2 (en) | 2016-08-30 | 2016-08-30 | Damshidin inducer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016168572A JP6995468B2 (en) | 2016-08-30 | 2016-08-30 | Damshidin inducer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2018035084A true JP2018035084A (en) | 2018-03-08 |
| JP6995468B2 JP6995468B2 (en) | 2022-01-14 |
Family
ID=61565412
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016168572A Active JP6995468B2 (en) | 2016-08-30 | 2016-08-30 | Damshidin inducer |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6995468B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2021060127A1 (en) * | 2019-09-24 | 2021-04-01 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07126172A (en) * | 1993-11-05 | 1995-05-16 | Genichiro Soma | Lps-containing anti-mrsa agent and anti-mrsa agent for animal |
| JPH08198902A (en) * | 1995-01-27 | 1996-08-06 | Denichi Mizuno | Low-molecular weight lipopolysaccharide |
| JP2016074654A (en) * | 2014-10-02 | 2016-05-12 | 日東電工株式会社 | Vaccine pharmaceutical composition for transdermal administration |
| JP2016147816A (en) * | 2015-02-10 | 2016-08-18 | 日東電工株式会社 | Vaccine composition for mucosal administration |
-
2016
- 2016-08-30 JP JP2016168572A patent/JP6995468B2/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07126172A (en) * | 1993-11-05 | 1995-05-16 | Genichiro Soma | Lps-containing anti-mrsa agent and anti-mrsa agent for animal |
| JPH08198902A (en) * | 1995-01-27 | 1996-08-06 | Denichi Mizuno | Low-molecular weight lipopolysaccharide |
| JP2016074654A (en) * | 2014-10-02 | 2016-05-12 | 日東電工株式会社 | Vaccine pharmaceutical composition for transdermal administration |
| JP2016147816A (en) * | 2015-02-10 | 2016-08-18 | 日東電工株式会社 | Vaccine composition for mucosal administration |
Non-Patent Citations (5)
| Title |
|---|
| ACTA MICROBIOLOGICA ET IMMUNOLOGICA HUNGARICA, vol. 51(3), JPN6020025399, 2004, pages 303 - 310, ISSN: 0004305455 * |
| JOURNAL OF BIOSCIENCE AND BIOENGINEERING, vol. 102(6), JPN6020025398, 2006, pages 485 - 496, ISSN: 0004305454 * |
| THE JOURNAL OF IMMUNOLOGY, vol. 174, JPN6020025401, 2005, pages 4870 - 4879, ISSN: 0004305456 * |
| アレルギー, vol. 第６５巻，第６号, JPN6020043282, 21 July 2016 (2016-07-21), pages 794 - 795, ISSN: 0004384453 * |
| 日本補完代謝医療学会誌, vol. 第４巻，第２号, JPN6020025396, 2007, pages 79 - 90, ISSN: 0004384452 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2021060127A1 (en) * | 2019-09-24 | 2021-04-01 | ||
| WO2021060127A1 (en) * | 2019-09-24 | 2021-04-01 | 有限会社バイオメディカルリサーチグループ | Lipopolysaccharide production method |
| CN114450312A (en) * | 2019-09-24 | 2022-05-06 | 生物医学研究集团有限公司 | Method for producing lipopolysaccharide |
| US20220372536A1 (en) * | 2019-09-24 | 2022-11-24 | Biomedical Research Group Inc. | Lipopolysaccharide production method |
| CN114450312B (en) * | 2019-09-24 | 2024-02-23 | 生物医学研究集团有限公司 | Method for producing lipopolysaccharide |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6995468B2 (en) | 2022-01-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kim et al. | Mucin degrader Akkermansia muciniphila accelerates intestinal stem cell-mediated epithelial development | |
| BRPI0507077A (en) | process for the preparation of l-amino acids using strains of the enterobacteriaceae family | |
| JP2011504366A5 (en) | ||
| CN108893523A (en) | A kind of fecal specimens room-temperature extender | |
| JP2017531425A5 (en) | ||
| WO2007099230A3 (en) | Expression system for yeast for the production of aromatic molecules | |
| JP2019536479A5 (en) | ||
| KR20180022984A (en) | Use of microbacterium strains for the production of antibacterial agents | |
| JP6995468B2 (en) | Damshidin inducer | |
| Landberg et al. | Characterization of cell-free breast cancer patient-derived scaffolds using liquid chromatography-mass spectrometry/mass spectrometry data and RNA sequencing data | |
| JP2011087486A5 (en) | ||
| JP2016086711A5 (en) | ||
| WO2017033925A1 (en) | Butyric acid-producing bacterium | |
| Wu et al. | The complete genome sequence of Bacillus velezensis LPL061, an exopolysaccharide-producing bacterium | |
| JP2006141242A (en) | Gene encoding methylated catechin biosynthesis enzime | |
| JPWO2018056150A1 (en) | Compound or salt thereof, anti-inflammatory agent, anticancer agent for lung cancer, method for producing compound or salt thereof, method for treating inflammatory disease, and method for treating lung cancer | |
| JPH10130269A (en) | Carboline derivative | |
| Jiang et al. | Enhancing CCL28 expression through the gene transfer to salivary glands for controlling cariogenic microbe | |
| JP2018538415A (en) | LPS extraction process | |
| CN108315375B (en) | Production method of oxidized nicotinamide adenine dinucleotide phosphate | |
| Zhang et al. | Efficient conversion from polysialogangliosides to monosialotetrahexosylganglioside using Oerskovia xanthineolytica YZ-2 | |
| JP2020115859A (en) | Novel microorganism having minimal genome and method of producing the same | |
| Zang et al. | Hyalangium ruber sp. nov, Characterization of a novel myxobacterium strain s54d21 and their secondary metabolites | |
| JP7521876B1 (en) | Anti-aging composition, anti-aging product, and method for producing same | |
| JP6489752B2 (en) | Non-human animal model possessing butyric acid-producing bacteria and method for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190703 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20200626 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200715 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200909 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20201111 |
|
| C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20210208 |
|
| C22 | Notice of designation (change) of administrative judge |
Free format text: JAPANESE INTERMEDIATE CODE: C22 Effective date: 20211013 |
|
| C23 | Notice of termination of proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C23 Effective date: 20211110 |
|
| C03 | Trial/appeal decision taken |
Free format text: JAPANESE INTERMEDIATE CODE: C03 Effective date: 20211215 |
|
| C30A | Notification sent |
Free format text: JAPANESE INTERMEDIATE CODE: C3012 Effective date: 20211215 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20211215 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6995468 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |