WO2024181023A1 - Composition - Google Patents
Composition Download PDFInfo
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- WO2024181023A1 WO2024181023A1 PCT/JP2024/003441 JP2024003441W WO2024181023A1 WO 2024181023 A1 WO2024181023 A1 WO 2024181023A1 JP 2024003441 W JP2024003441 W JP 2024003441W WO 2024181023 A1 WO2024181023 A1 WO 2024181023A1
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- WO
- WIPO (PCT)
- Prior art keywords
- green alga
- alga chlamydomonas
- extract
- chlamydomonas
- composition
- Prior art date
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Definitions
- the present invention relates to a composition containing the green alga Chlamydomonas or an extract of the green alga Chlamydomonas.
- Patent Document 1 describes a drug that specifically binds to opioid receptors.
- Patent Document 2 describes the Hyundai DREAMO strain (accession number FERM BP-22306) as an example of the green alga Chlamydomonas reinhardtii.
- the present invention aims to provide a composition containing as an active ingredient the green alga Chlamydomonas or an extract of the green alga Chlamydomonas, which functions as an agonist of opioid receptors.
- a composition comprising the green alga Chlamydomonas reinhardtii or an extract of the green alga Chlamydomonas reinhardtii, wherein the green alga Chlamydomonas reinhardtii or the extract of the green alga Chlamydomonas reinhardtii contains an agonist of an opioid receptor.
- composition according to (1) or (2) which is an emetic, antiperistaltic agent, or antidiarrheal agent.
- the present invention provides a composition containing as an active ingredient the green alga Chlamydomonas or an extract of the green alga Chlamydomonas, which functions as an agonist of opioid receptors.
- composition of this embodiment contains the green algae Chlamydomonas reinhardtii or an extract of the green algae Chlamydomonas reinhardtii, and the green algae Chlamydomonas reinhardtii or an extract of the green algae Chlamydomonas reinhardtii contains an agonist of the opioid receptor.
- the green alga Chlamydomonas is not particularly limited, but examples thereof include the UTEX 90 strain and the Hyundai DREAMO strain (accession number FERM BP-22306).
- the UTEX 90 strain is the parent strain of the Hyundai DREAMO strain.
- the green alga Chlamydomonas is preferably a freshwater alga, which allows it to be cultivated in large quantities on land.
- opioid receptors examples include ⁇ opioid receptors ( ⁇ 1 opioid receptors and ⁇ 2 opioid receptors), ⁇ opioid receptors ( ⁇ 1 opioid receptors, ⁇ 2 opioid receptors and ⁇ 3 opioid receptors), and ⁇ opioid receptors ( ⁇ 1 opioid receptors and ⁇ 2 opioid receptors).
- ⁇ opioid receptors are preferred, and ⁇ 1 opioid receptors are more preferred.
- composition of this embodiment contains as an active ingredient the green alga Chlamydomonas reinhardtii or an extract of the green alga Chlamydomonas reinhardtii, which functions as an agonist of the opioid receptor, and can therefore be used in pharmaceuticals such as emetics, peristalsis inhibitors, and diarrhea treatments.
- diarrhea include acute diarrhea.
- the dosage form of the medicine may be either oral (internal) or parenteral (external, injection).
- the dosage form of the pharmaceutical product is not particularly limited, but examples include solid preparations such as tablets, granules, powders, and capsules, liquid preparations such as solutions, suspensions, and emulsions, and freeze-dried preparations.
- the pharmaceutical product can be manufactured using known methods.
- composition of this embodiment may be applied to, for example, quasi-drugs, cosmetics, and foods.
- composition of this embodiment is preferably for use in humans, but may also be for use in animals other than humans.
- the method for culturing the green alga Chlamydomonas is not particularly limited, and examples include static culture, shaking culture, submerged culture, and aeration culture.
- the green alga Chlamydomonas can be cultivated in large quantities on land by culturing it outdoors.
- Methods for culturing the green alga Chlamydomonas outdoors are not particularly limited, but examples include a method of culturing it in an open pond using a raceway-type bioreactor, and a method of culturing it in a flat-panel photobioreactor installed outdoors.
- the medium used to culture the green alga Chlamydomonas is not particularly limited, but examples include TAP medium, urea medium, HSM medium, BG11 medium, etc.
- the temperature at which the green alga Chlamydomonas is cultured is not particularly limited, but is, for example, between 2°C and 38°C.
- the light-dark cycle for culturing the green alga Chlamydomonas is not particularly limited, but for example, is a 24-hour cycle with the light period being 6 hours or more and 24 hours or less.
- the photosynthetically active photon flux density during the light period is not particularly limited, but is, for example, 50 ⁇ mol/m 2 /s or more and 2000 ⁇ mol/m 2 /s or less.
- the amount of gas aeration per unit volume when culturing the green alga Chlamydomonas using the aeration culture method is not particularly limited, but is, for example, 0.001 VVM or more and 10 VVM or less. Note that VVM indicates how many times the volume of gas is aerated relative to the culture medium in one minute.
- the concentration of carbon dioxide in the gas to be aerated is not particularly limited, but is, for example, 0.1% by volume or more and 10% by volume or less.
- the source of carbon dioxide is not particularly limited, but examples include carbon dioxide cylinders, gas discharged from factories, and concentrated carbon dioxide captured from the atmosphere by DAC (Direct Air Capture).
- Methods for recovering the cultured green alga Chlamydomonas are not particularly limited, but include, for example, centrifugation, filtration, etc.
- the recovered Chlamydomonas may be dried if necessary.
- Methods for drying the green alga Chlamydomonas are not particularly limited, but examples include freeze-drying, spray-drying, hot air drying, and sun drying.
- the extraction method used to extract the green alga Chlamydomonas is not particularly limited, but examples include ultrasonic extraction.
- the solvent used for extraction of the green alga Chlamydomonas is not particularly limited, but examples include lower alcohols such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, and glycerin; and hydrophilic organic solvents such as dimethyl sulfoxide (DMSO). Of these, DMSO is preferred.
- the method for recovering an extract of the green alga Chlamydomonas is not particularly limited, but examples include centrifugation and filtration.
- the recovered extract of the green alga Chlamydomonas may be dried if necessary.
- the method for drying the extract of the green alga Chlamydomonas is not particularly limited, but examples include freeze-drying.
- the recovered Honda DREAMO strain was statically cultured (precultured) for 7 days using 2 L of TAP medium under the same culture conditions as the seed culture.
- the precultured Honda DREAMO strain was aerated (main culture) for 7 days using 5 L of urea medium under the same culture conditions as those for the seed culture.
- the aeration conditions were as follows: Gas flow rate per unit volume: 0.15 VVM Concentration of carbon dioxide in gas: 5% by volume
- the mixture of extract and residue was then centrifuged at 3000 rpm for 5 minutes, the residue was removed, and approximately 100 mL of extract was recovered.
- the extract was then freeze-dried to obtain 490.74 mg of Hyundai DREAMO strain extract.
- the DMSO solution of the Honda DREAMO strain extract was centrifuged at 15,000 rpm for 5 seconds, and the supernatant was collected to obtain the sample.
- the maximum concentration at which there was no evidence of inhibition of cell proliferation or an effect on the optical density of the sample 100 ⁇ g/mL, was determined as the sample concentration in the assay.
- Assays of samples targeting ⁇ 1 opioid receptors were performed at a sample concentration of 100 ⁇ g/mL. The number of assays was two. The assays were outsourced to Eurofins Pharma Discovery Services, and were performed using two different assay systems to eliminate false positives. Target molecules with an activation rate of 50% or more were determined to act as agonists.
- Table 1 shows the assay results for the samples.
- the extract of Honda DREAMO strain contained in the sample contains an agonist of the ⁇ 1 opioid receptor, that is, it functions as an agonist of the ⁇ 1 opioid receptor.
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- Medicines Containing Plant Substances (AREA)
Abstract
Provided is a composition containing Chlamydomonas reinhardtii or an extract of Chlamydomonas reinhardtii, wherein the Chlamydomonas reinhardtii or the extract of the Chlamydomonas reinhardtii contains an agonist of an opioid receptor.
Description
本発明は、緑藻クラミドモナスまたは緑藻クラミドモナスの抽出物を含む組成物に関する。
The present invention relates to a composition containing the green alga Chlamydomonas or an extract of the green alga Chlamydomonas.
あらゆる年齢のすべての人々の健康的な生活を確保し、福祉を促進するために、医薬品の開発が進められている。
Medicines are developed to ensure healthy lives and promote well-being for all people at all ages.
特許文献１には、オピオイド受容体に特異的に結合する薬剤が記載されている。
Patent Document 1 describes a drug that specifically binds to opioid receptors.
一方、特許文献２には、緑藻クラミドモナス（Ｃｈｌａｍｙｄｏｍｏｎａｓ ｒｅｉｎｈａｒｄｔｉｉ）の一例として、Ｈｏｎｄａ ＤＲＥＡＭＯ株（受託番号ＦＥＲＭ ＢＰ－２２３０６）が記載されている。
On the other hand, Patent Document 2 describes the Honda DREAMO strain (accession number FERM BP-22306) as an example of the green alga Chlamydomonas reinhardtii.
しかしながら、緑藻クラミドモナスまたは緑藻クラミドモナスの抽出物がオピオイド受容体のアゴニストとして機能することは知られていない。
However, it is not known that the green alga Chlamydomonas reinhardtii or extracts of the green alga Chlamydomonas reinhardtii function as opioid receptor agonists.
本発明は、オピオイド受容体のアゴニストとして機能する緑藻クラミドモナスまたは緑藻クラミドモナスの抽出物を有効成分とする組成物を提供することを目的とする。
The present invention aims to provide a composition containing as an active ingredient the green alga Chlamydomonas or an extract of the green alga Chlamydomonas, which functions as an agonist of opioid receptors.
（１）緑藻クラミドモナスまたは緑藻クラミドモナスの抽出物を含む組成物であって、前記緑藻クラミドモナスまたは前記緑藻クラミドモナスの抽出物は、オピオイド受容体のアゴニストを含む、組成物。
(1) A composition comprising the green alga Chlamydomonas reinhardtii or an extract of the green alga Chlamydomonas reinhardtii, wherein the green alga Chlamydomonas reinhardtii or the extract of the green alga Chlamydomonas reinhardtii contains an agonist of an opioid receptor.
（２）前記緑藻クラミドモナスは、Ｈｏｎｄａ ＤＲＥＡＭＯ株（受託番号ＦＥＲＭ ＢＰ－２２３０６）である、（１）に記載の組成物。
(2) The composition described in (1), in which the green alga Chlamydomonas is the Honda DREAMO strain (accession number FERM BP-22306).
（３）吐瀉薬、蠕動抑制薬または下痢症治療薬である、（１）または（２）に記載の組成物。
(3) The composition according to (1) or (2), which is an emetic, antiperistaltic agent, or antidiarrheal agent.
（４）前記オピオイド受容体は、μ１オピオイド受容体である、（１）から（３）のいずれか一項に記載の組成物。
(4) The composition according to any one of (1) to (3), wherein the opioid receptor is a μ1 opioid receptor.
（５）前記緑藻クラミドモナスは、淡水藻である、（１）から（４）のいずれか一項に記載の組成物。
(5) The composition according to any one of (1) to (4), wherein the green alga Chlamydomonas is a freshwater alga.
本発明によれば、オピオイド受容体のアゴニストとして機能する緑藻クラミドモナスまたは緑藻クラミドモナスの抽出物を有効成分とする組成物を提供することができる。
The present invention provides a composition containing as an active ingredient the green alga Chlamydomonas or an extract of the green alga Chlamydomonas, which functions as an agonist of opioid receptors.
以下、本発明の実施形態について説明する。
The following describes an embodiment of the present invention.
本実施形態の組成物は、緑藻クラミドモナスまたは緑藻クラミドモナスの抽出物を含み、緑藻クラミドモナスまたは緑藻クラミドモナスの抽出物は、オピオイド受容体のアゴニストを含む。
The composition of this embodiment contains the green algae Chlamydomonas reinhardtii or an extract of the green algae Chlamydomonas reinhardtii, and the green algae Chlamydomonas reinhardtii or an extract of the green algae Chlamydomonas reinhardtii contains an agonist of the opioid receptor.
緑藻クラミドモナスとしては、特に限定されないが、例えば、ＵＴＥＸ ９０株、Ｈｏｎｄａ ＤＲＥＡＭＯ株（受託番号ＦＥＲＭ ＢＰ－２２３０６）が挙げられる。ここで、ＵＴＥＸ ９０株は、Ｈｏｎｄａ ＤＲＥＡＭＯ株の元株である。
The green alga Chlamydomonas is not particularly limited, but examples thereof include the UTEX 90 strain and the Honda DREAMO strain (accession number FERM BP-22306). Here, the UTEX 90 strain is the parent strain of the Honda DREAMO strain.
緑藻クラミドモナスは、淡水藻であることが好ましい。これにより、陸上で大量に培養することができる。
The green alga Chlamydomonas is preferably a freshwater alga, which allows it to be cultivated in large quantities on land.
オピオイド受容体としては、δオピオイド受容体（δ１オピオイド受容体およびδ２オピオイド受容体）、κオピオイド受容体（κ１オピオイド受容体、κ２オピオイド受容体およびκ３オピオイド受容体）、μオピオイド受容体（μ１オピオイド受容体およびμ２オピオイド受容体）が挙げられる。これらの中でも、μオピオイド受容体が好ましく、μ１オピオイド受容体がさらに好ましい。
Examples of opioid receptors include δ opioid receptors ( δ1 opioid receptors and δ2 opioid receptors), κ opioid receptors ( κ1 opioid receptors, κ2 opioid receptors and κ3 opioid receptors), and μ opioid receptors ( μ1 opioid receptors and μ2 opioid receptors). Among these, μ opioid receptors are preferred, and μ1 opioid receptors are more preferred.
本実施形態の組成物は、オピオイド受容体のアゴニストとして機能する緑藻クラミドモナスまたは緑藻クラミドモナスの抽出物を有効成分とするため、吐瀉薬、蠕動抑制薬、下痢症治療薬等の医薬品に適用することができる。下痢症としては、例えば、急性下痢症が挙げられる。
The composition of this embodiment contains as an active ingredient the green alga Chlamydomonas reinhardtii or an extract of the green alga Chlamydomonas reinhardtii, which functions as an agonist of the opioid receptor, and can therefore be used in pharmaceuticals such as emetics, peristalsis inhibitors, and diarrhea treatments. Examples of diarrhea include acute diarrhea.
医薬品の投与形態は、経口投与（内用）および非経口投与（外用、注射）のいずれであってもよい。
The dosage form of the medicine may be either oral (internal) or parenteral (external, injection).
医薬品の剤型としては、特に限定されないが、例えば、錠剤、顆粒剤、散剤、カプセル剤等の固形剤、溶液剤、懸濁剤、乳剤等の液剤、凍結乾燥製剤等が挙げられる。
The dosage form of the pharmaceutical product is not particularly limited, but examples include solid preparations such as tablets, granules, powders, and capsules, liquid preparations such as solutions, suspensions, and emulsions, and freeze-dried preparations.
医薬品は、公知の方法を用いて、製造することができる。
The pharmaceutical product can be manufactured using known methods.
本実施形態の組成物は、例えば、医薬部外品、化粧料、食品に適用してもよい。
The composition of this embodiment may be applied to, for example, quasi-drugs, cosmetics, and foods.
本実施形態の組成物は、ヒト用であることが好ましいが、ヒト以外の動物用であってもよい。
The composition of this embodiment is preferably for use in humans, but may also be for use in animals other than humans.
緑藻クラミドモナスの培養方法としては、特に限定されず、例えば、静置培養法、振盪培養法、深部培養法、通気培養法等が挙げられる。
The method for culturing the green alga Chlamydomonas is not particularly limited, and examples include static culture, shaking culture, submerged culture, and aeration culture.
緑藻クラミドモナスは、屋外で培養することにより、陸上で大量に培養することができる。緑藻クラミドモナスを屋外で培養する方法としては、特に限定されないが、例えば、レースウェイ型のバイオリアクターを用いて、オープンポンド方式で培養する方法、フラットパネル型フォトバイオリアクターを屋外に設置して培養する方法等が挙げられる。
The green alga Chlamydomonas can be cultivated in large quantities on land by culturing it outdoors. Methods for culturing the green alga Chlamydomonas outdoors are not particularly limited, but examples include a method of culturing it in an open pond using a raceway-type bioreactor, and a method of culturing it in a flat-panel photobioreactor installed outdoors.
緑藻クラミドモナスを培養する際に用いる培地としては、特に限定されないが、例えば、ＴＡＰ培地、ウレア培地、ＨＳＭ培地、ＢＧ１１培地等が挙げられる。
The medium used to culture the green alga Chlamydomonas is not particularly limited, but examples include TAP medium, urea medium, HSM medium, BG11 medium, etc.
緑藻クラミドモナスを培養する際の温度は、特に限定されないが、例えば、２℃以上３８℃以下である。
The temperature at which the green alga Chlamydomonas is cultured is not particularly limited, but is, for example, between 2°C and 38°C.
緑藻クラミドモナスを培養する際の明暗周期は、特に限定されないが、例えば、明期が６時間以上２４時間以下の２４時間周期である。
The light-dark cycle for culturing the green alga Chlamydomonas is not particularly limited, but for example, is a 24-hour cycle with the light period being 6 hours or more and 24 hours or less.
明期の光合成有効光量子束密度は、特に限定されないが、例えば、５０μｍｏｌ／ｍ２／ｓ以上２０００μｍｏｌ／ｍ２／ｓ以下である。
The photosynthetically active photon flux density during the light period is not particularly limited, but is, for example, 50 μmol/m 2 /s or more and 2000 μmol/m 2 /s or less.
通気培養法によって緑藻クラミドモナスを培養する際の単位体積当たりのガス通気量は、特に限定されないが、例えば、０．００１ＶＶＭ以上１０ＶＶＭ以下である。なお、ＶＶＭは、１分間で、培地に対して、体積比で何倍のガスを通気するかを示すものである。
The amount of gas aeration per unit volume when culturing the green alga Chlamydomonas using the aeration culture method is not particularly limited, but is, for example, 0.001 VVM or more and 10 VVM or less. Note that VVM indicates how many times the volume of gas is aerated relative to the culture medium in one minute.
通気培養法によって緑藻クラミドモナスを培養する際に、培地に二酸化炭素を供給することが好ましい。通気するガス中の二酸化炭素の濃度は、特に限定されないが、例えば、０．１体積％以上１０体積％以下である。なお、二酸化炭素の供給源としては、特に限定されないが、例えば、二酸化炭素ボンベ、工場等から排出されたガス、ＤＡＣ（Ｄｉｒｅｃｔ Ａｉｒ Ｃａｐｔｕｒｅ）によって大気中から回収された濃縮二酸化炭素等が挙げられる。
When culturing the green alga Chlamydomonas by aeration culture, it is preferable to supply carbon dioxide to the medium. The concentration of carbon dioxide in the gas to be aerated is not particularly limited, but is, for example, 0.1% by volume or more and 10% by volume or less. The source of carbon dioxide is not particularly limited, but examples include carbon dioxide cylinders, gas discharged from factories, and concentrated carbon dioxide captured from the atmosphere by DAC (Direct Air Capture).
培養された緑藻クラミドモナスを回収する方法としては、特に限定されないが、例えば、遠心分離法、濾過法等が挙げられる。
Methods for recovering the cultured green alga Chlamydomonas are not particularly limited, but include, for example, centrifugation, filtration, etc.
なお、回収された緑藻クラミドモナスは、必要に応じて、乾燥させてもよい。
The recovered Chlamydomonas may be dried if necessary.
緑藻クラミドモナスを乾燥させる方法としては、特に限定されないが、例えば、凍結乾燥法、スプレードライ法、温風乾燥法、天日干し法等が挙げられる。
Methods for drying the green alga Chlamydomonas are not particularly limited, but examples include freeze-drying, spray-drying, hot air drying, and sun drying.
緑藻クラミドモナスの抽出に用いる抽出法としては、特に限定されないが、例えば、超音波抽出法等が挙げられる。
The extraction method used to extract the green alga Chlamydomonas is not particularly limited, but examples include ultrasonic extraction.
緑藻クラミドモナスの抽出に用いる溶媒としては、特に限定されないが、例えば、メタノール、エタノール、プロピルアルコール、イソプロピルアルコール等の低級アルコール；アセトン、メチルエチルケトン等の低級脂肪族ケトン；１，３－ブチレングリコール、プロピレングリコール、グリセリン等の多価アルコール；ジメチルスルホキシド（ＤＭＳＯ）等の親水性有機溶媒が挙げられる。これらの中でも、ＤＭＳＯが好ましい。
The solvent used for extraction of the green alga Chlamydomonas is not particularly limited, but examples include lower alcohols such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, and glycerin; and hydrophilic organic solvents such as dimethyl sulfoxide (DMSO). Of these, DMSO is preferred.
緑藻クラミドモナスの抽出液を回収する方法としては、特に限定されないが、例えば、遠心分離法、濾過法等が挙げられる。
The method for recovering an extract of the green alga Chlamydomonas is not particularly limited, but examples include centrifugation and filtration.
なお、回収された緑藻クラミドモナスの抽出物は、必要に応じて、乾燥させてもよい。
The recovered extract of the green alga Chlamydomonas may be dried if necessary.
緑藻クラミドモナスの抽出物を乾燥させる方法としては、特に限定されないが、例えば、凍結乾燥法等が挙げられる。
The method for drying the extract of the green alga Chlamydomonas is not particularly limited, but examples include freeze-drying.
以下、本発明の実施例を説明するが、本発明は、実施例に限定されるものではない。
The following describes examples of the present invention, but the present invention is not limited to these examples.
［実施例１］
［緑藻クラミドモナスの培養］
ＴＡＰ培地２Ｌを用いて、以下に示す培養条件で緑藻クラミドモナスとしての、Ｈｏｎｄａ ＤＲＥＡＭＯ株を５日間静置培養（種培養）した。 [Example 1]
[Cultivation of the green alga Chlamydomonas]
Honda DREAMO strain of Chlamydomonas reinhardtii was statically cultured (seed culture) for 5 days in 2 L of TAP medium under the culture conditions shown below.
［緑藻クラミドモナスの培養］
ＴＡＰ培地２Ｌを用いて、以下に示す培養条件で緑藻クラミドモナスとしての、Ｈｏｎｄａ ＤＲＥＡＭＯ株を５日間静置培養（種培養）した。 [Example 1]
[Cultivation of the green alga Chlamydomonas]
Honda DREAMO strain of Chlamydomonas reinhardtii was statically cultured (seed culture) for 5 days in 2 L of TAP medium under the culture conditions shown below.
温度：２５℃
明暗周期：明期１２時間、暗期１２時間
明期の光合成有効光量子束密度：６０～８０μｍｏｌ／ｍ２／ｓ
光源：白色ＬＥＤ
次に、種培養物５００ｍＬを３０００ｒｐｍで５分間遠心分離した後、培養上清液を除去し、種培養されたＨｏｎｄａ ＤＲＥＡＭＯ株を回収した。 Temperature: 25°C
Light/dark cycle: 12 hours light, 12 hours dark Photosynthetic photon flux density during light period: 60-80 μmol/m 2 /s
Light source: White LED
Next, 500 mL of the seed culture was centrifuged at 3,000 rpm for 5 minutes, and the culture supernatant was removed to recover the seed-cultured Honda DREAMO strain.
明暗周期：明期１２時間、暗期１２時間
明期の光合成有効光量子束密度：６０～８０μｍｏｌ／ｍ２／ｓ
光源：白色ＬＥＤ
次に、種培養物５００ｍＬを３０００ｒｐｍで５分間遠心分離した後、培養上清液を除去し、種培養されたＨｏｎｄａ ＤＲＥＡＭＯ株を回収した。 Temperature: 25°C
Light/dark cycle: 12 hours light, 12 hours dark Photosynthetic photon flux density during light period: 60-80 μmol/m 2 /s
Light source: White LED
Next, 500 mL of the seed culture was centrifuged at 3,000 rpm for 5 minutes, and the culture supernatant was removed to recover the seed-cultured Honda DREAMO strain.
次に、ＴＡＰ培地２Ｌを用いて、種培養と同一の培養条件で、回収されたＨｏｎｄａ ＤＲＥＡＭＯ株を７日間静置培養（前培養）した。
Next, the recovered Honda DREAMO strain was statically cultured (precultured) for 7 days using 2 L of TAP medium under the same culture conditions as the seed culture.
次に、ウレア培地５Ｌを用いて、種培養と同一の培養条件で、前培養されたＨｏｎｄａ ＤＲＥＡＭＯ株を７日間通気培養（本培養）した。なお、通気条件は、以下の通りである。
単位体積当たりのガス通気量：０．１５ＶＶＭ
ガス中の二酸化炭素の濃度：５体積％ Next, the precultured Honda DREAMO strain was aerated (main culture) for 7 days using 5 L of urea medium under the same culture conditions as those for the seed culture. The aeration conditions were as follows:
Gas flow rate per unit volume: 0.15 VVM
Concentration of carbon dioxide in gas: 5% by volume
単位体積当たりのガス通気量：０．１５ＶＶＭ
ガス中の二酸化炭素の濃度：５体積％ Next, the precultured Honda DREAMO strain was aerated (main culture) for 7 days using 5 L of urea medium under the same culture conditions as those for the seed culture. The aeration conditions were as follows:
Gas flow rate per unit volume: 0.15 VVM
Concentration of carbon dioxide in gas: 5% by volume
次に、本培養物５Ｌを６０００ｒｐｍで１０分間遠心分離した後、培養上清液を除去し、本培養されたＨｏｎｄａ ＤＲＥＡＭＯ株を回収した。
Next, 5 L of the main culture was centrifuged at 6,000 rpm for 10 minutes, the culture supernatant was removed, and the cultured Honda DREAMO strain was recovered.
［抽出］
超音波ホモジナイザーを用いて、回収されたＨｏｎｄａ ＤＲＥＡＭＯ株約２０ｍＬをＤＭＳＯ１００ｍＬで５分間超音波抽出した。このとき、超音波抽出を氷上で実施した。 [extraction]
About 20 mL of the collected Honda DREAMO strain was subjected to ultrasonic extraction with 100 mL of DMSO for 5 minutes using an ultrasonic homogenizer. The ultrasonic extraction was carried out on ice.
超音波ホモジナイザーを用いて、回収されたＨｏｎｄａ ＤＲＥＡＭＯ株約２０ｍＬをＤＭＳＯ１００ｍＬで５分間超音波抽出した。このとき、超音波抽出を氷上で実施した。 [extraction]
About 20 mL of the collected Honda DREAMO strain was subjected to ultrasonic extraction with 100 mL of DMSO for 5 minutes using an ultrasonic homogenizer. The ultrasonic extraction was carried out on ice.
次に、抽出液と残渣の混合物を３０００ｒｐｍで５分間遠心分離した後、残渣を除去し、抽出液約１００ｍＬを回収した。
The mixture of extract and residue was then centrifuged at 3000 rpm for 5 minutes, the residue was removed, and approximately 100 mL of extract was recovered.
次に、抽出液を凍結乾燥させ、Ｈｏｎｄａ ＤＲＥＡＭＯ株の抽出物４９０．７４ｍｇを得た。
The extract was then freeze-dried to obtain 490.74 mg of Honda DREAMO strain extract.
［検体の作製］
超音波ホモジナイザーを用いて、Ｈｏｎｄａ ＤＲＥＡＭＯ株の抽出物４９０ｍｇをＤＭＳＯ４．９ｍＬに溶解させ、１００ｍｇ／ｍＬのＨｏｎｄａ ＤＲＥＡＭＯ株の抽出物のＤＭＳＯ溶液を得た。 [Preparation of specimen]
Using an ultrasonic homogenizer, 490 mg of the extract of Honda DREAMO strain was dissolved in 4.9 mL of DMSO to obtain a 100 mg/mL DMSO solution of the extract of Honda DREAMO strain.
超音波ホモジナイザーを用いて、Ｈｏｎｄａ ＤＲＥＡＭＯ株の抽出物４９０ｍｇをＤＭＳＯ４．９ｍＬに溶解させ、１００ｍｇ／ｍＬのＨｏｎｄａ ＤＲＥＡＭＯ株の抽出物のＤＭＳＯ溶液を得た。 [Preparation of specimen]
Using an ultrasonic homogenizer, 490 mg of the extract of Honda DREAMO strain was dissolved in 4.9 mL of DMSO to obtain a 100 mg/mL DMSO solution of the extract of Honda DREAMO strain.
次に、Ｈｏｎｄａ ＤＲＥＡＭＯ株の抽出物のＤＭＳＯ溶液を１５０００ｒｐｍで５秒間遠心分離した後、上清を回収し、検体を得た。
Next, the DMSO solution of the Honda DREAMO strain extract was centrifuged at 15,000 rpm for 5 seconds, and the supernatant was collected to obtain the sample.
次に、アッセイ（ｉｎ ｖｉｔｒｏ機能性評価試験）に用いる検体の濃度を決定するために、以下の２種類の試験を実施した。
［細胞増殖抑制試験］
Ｄ－ＭＥＭ（Ｈｉｇｈ Ｇｌｕｃｏｓｅ）＋１０％ＦＢＳ＋１％Ｐｅｎｉｃｉｌｌｉｎ－Ｓｔｒｅｐｔｏｍｙｃｉｎ培地で生育させたＨＥＫ２９３細胞（ヒト胎児腎細胞由来細胞株）に１３種類の濃度（０，１０，２０，３０，４０，５０，６０，７０，８０，９０，１００，２５０，５００μｇ／ｍＬ）で検体を添加し、用量依存性試験を実施した。検体を細胞に添加してから２４時間後に培地を交換し、細胞をＷＳＴ－８で４時間染色した。次に、ＦｌｅｘＳｔａｔｉｏｎ ３ マルチモードマイクロプレートリーダー（Ｍｏｌｅｃｕｌａｒ Ｄｅｖｉｃｅｓ製）を用いて、波長４５０ｎｍの光学密度（Ｏ．Ｄ．）を測定した。ここで、上記試験は、ｎ＝３で実施した。 Next, in order to determine the concentration of the sample to be used in the assay (in vitro functionality evaluation test), the following two types of tests were carried out.
[Cytoinhibition test]
The sample was added at 13 concentrations (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500 μg / mL) to HEK293 cells (human fetal kidney cell-derived cell line) grown in D-MEM (High Glucose) + 10% FBS + 1% Penicillin-Streptomycin medium, and a dose-dependency test was performed. 24 hours after adding the sample to the cells, the medium was replaced, and the cells were stained with WST-8 for 4 hours. Next, the optical density (O.D.) at a wavelength of 450 nm was measured using a FlexStation 3 multimode microplate reader (Molecular Devices). Here, the above test was performed with n = 3.
［細胞増殖抑制試験］
Ｄ－ＭＥＭ（Ｈｉｇｈ Ｇｌｕｃｏｓｅ）＋１０％ＦＢＳ＋１％Ｐｅｎｉｃｉｌｌｉｎ－Ｓｔｒｅｐｔｏｍｙｃｉｎ培地で生育させたＨＥＫ２９３細胞（ヒト胎児腎細胞由来細胞株）に１３種類の濃度（０，１０，２０，３０，４０，５０，６０，７０，８０，９０，１００，２５０，５００μｇ／ｍＬ）で検体を添加し、用量依存性試験を実施した。検体を細胞に添加してから２４時間後に培地を交換し、細胞をＷＳＴ－８で４時間染色した。次に、ＦｌｅｘＳｔａｔｉｏｎ ３ マルチモードマイクロプレートリーダー（Ｍｏｌｅｃｕｌａｒ Ｄｅｖｉｃｅｓ製）を用いて、波長４５０ｎｍの光学密度（Ｏ．Ｄ．）を測定した。ここで、上記試験は、ｎ＝３で実施した。 Next, in order to determine the concentration of the sample to be used in the assay (in vitro functionality evaluation test), the following two types of tests were carried out.
[Cytoinhibition test]
The sample was added at 13 concentrations (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500 μg / mL) to HEK293 cells (human fetal kidney cell-derived cell line) grown in D-MEM (High Glucose) + 10% FBS + 1% Penicillin-Streptomycin medium, and a dose-dependency test was performed. 24 hours after adding the sample to the cells, the medium was replaced, and the cells were stained with WST-8 for 4 hours. Next, the optical density (O.D.) at a wavelength of 450 nm was measured using a FlexStation 3 multimode microplate reader (Molecular Devices). Here, the above test was performed with n = 3.
その結果、いずれの検体の濃度においても、光学密度の減少は認められなかったため、濃度による影響はないと判断した。
As a result, no decrease in optical density was observed at any sample concentration, so it was determined that there was no effect due to concentration.
［検体の光学密度への影響］
Ｄ－ＭＥＭ（Ｈｉｇｈ Ｇｌｕｃｏｓｅ）＋１０％ＦＢＳ＋１％Ｐｅｎｉｃｉｌｌｉｎ－Ｓｔｒｅｐｔｏｍｙｃｉｎ培地に１３種類の濃度（０，１０，２０，３０，４０，５０，６０，７０，８０，９０，１００，２５０，５００μｇ／ｍＬ）で検体を添加してから２４時間後に培地を交換し、ＷＳＴ－８で４時間染色した。次に、ＦｌｅｘＳｔａｔｉｏｎ ３ マルチモードマイクロプレートリーダー（Ｍｏｌｅｃｕｌａｒ Ｄｅｖｉｃｅｓ製）を用いて、波長４５０ｎｍの光学密度を測定した。ここで、上記試験は、ｎ＝３で実施した。 Effect of sample on optical density
The samples were added to D-MEM (High Glucose) + 10% FBS + 1% Penicillin-Streptomycin medium at 13 different concentrations (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500 μg/mL) and the medium was replaced 24 hours later, and stained with WST-8 for 4 hours. Next, the optical density at a wavelength of 450 nm was measured using a FlexStation 3 multimode microplate reader (Molecular Devices). Here, the above test was performed with n=3.
Ｄ－ＭＥＭ（Ｈｉｇｈ Ｇｌｕｃｏｓｅ）＋１０％ＦＢＳ＋１％Ｐｅｎｉｃｉｌｌｉｎ－Ｓｔｒｅｐｔｏｍｙｃｉｎ培地に１３種類の濃度（０，１０，２０，３０，４０，５０，６０，７０，８０，９０，１００，２５０，５００μｇ／ｍＬ）で検体を添加してから２４時間後に培地を交換し、ＷＳＴ－８で４時間染色した。次に、ＦｌｅｘＳｔａｔｉｏｎ ３ マルチモードマイクロプレートリーダー（Ｍｏｌｅｃｕｌａｒ Ｄｅｖｉｃｅｓ製）を用いて、波長４５０ｎｍの光学密度を測定した。ここで、上記試験は、ｎ＝３で実施した。 Effect of sample on optical density
The samples were added to D-MEM (High Glucose) + 10% FBS + 1% Penicillin-Streptomycin medium at 13 different concentrations (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 250, 500 μg/mL) and the medium was replaced 24 hours later, and stained with WST-8 for 4 hours. Next, the optical density at a wavelength of 450 nm was measured using a FlexStation 3 multimode microplate reader (Molecular Devices). Here, the above test was performed with n=3.
その結果、検体の濃度が２５０μｇ／ｍＬおよび５００μｇ／ｍＬである場合に、光学密度の上昇が認められた。このため、２５０μｇ／ｍＬおよび５００μｇ／ｍＬで検体を添加した場合には、細胞とは関係なく、光学密度に影響を与えることがわかった。一方、１００μｇ／ｍＬ以下の濃度で検体を添加した場合には、光学密度に影響を与えないことがわかった。
As a result, an increase in optical density was observed when the sample concentration was 250 μg/mL and 500 μg/mL. This shows that adding a sample at 250 μg/mL and 500 μg/mL has an effect on optical density, regardless of the cells. On the other hand, adding a sample at a concentration of 100 μg/mL or less had no effect on optical density.
以上の結果より、細胞増殖抑制および検体の光学密度への影響が認められなかった濃度の最大値である１００μｇ／ｍＬを、アッセイにおける検体濃度とした。
Based on these results, the maximum concentration at which there was no evidence of inhibition of cell proliferation or an effect on the optical density of the sample, 100 μg/mL, was determined as the sample concentration in the assay.
［アッセイ］
μ１オピオイド受容体を標的分子とする検体のアッセイを、検体濃度１００μｇ／ｍＬで実施した。ここで、アッセイの繰り返し数は２とした。なお、アッセイは、Ｅｕｒｏｆｉｎｓ Ｐｈａｒｍａ Ｄｉｓｃｏｖｅｒｙ Ｓｅｒｖｉｃｅｓに委託し、疑似陽性を排除するために２種類のアッセイ系で実施した。ここで、作動率が５０％以上である標的分子をアゴニストとしての作用があると判断した。 [Assay]
Assays of samples targeting μ1 opioid receptors were performed at a sample concentration of 100 μg/mL. The number of assays was two. The assays were outsourced to Eurofins Pharma Discovery Services, and were performed using two different assay systems to eliminate false positives. Target molecules with an activation rate of 50% or more were determined to act as agonists.
μ１オピオイド受容体を標的分子とする検体のアッセイを、検体濃度１００μｇ／ｍＬで実施した。ここで、アッセイの繰り返し数は２とした。なお、アッセイは、Ｅｕｒｏｆｉｎｓ Ｐｈａｒｍａ Ｄｉｓｃｏｖｅｒｙ Ｓｅｒｖｉｃｅｓに委託し、疑似陽性を排除するために２種類のアッセイ系で実施した。ここで、作動率が５０％以上である標的分子をアゴニストとしての作用があると判断した。 [Assay]
Assays of samples targeting μ1 opioid receptors were performed at a sample concentration of 100 μg/mL. The number of assays was two. The assays were outsourced to Eurofins Pharma Discovery Services, and were performed using two different assay systems to eliminate false positives. Target molecules with an activation rate of 50% or more were determined to act as agonists.
表１に、検体のアッセイの結果を示す。
Table 1 shows the assay results for the samples.
表１から、検体に含まれるＨｏｎｄａ ＤＲＥＡＭＯ株の抽出物がμ１オピオイド受容体のアゴニストを含む、すなわち、μ１オピオイド受容体のアゴニストとして機能することがわかる。
From Table 1, it can be seen that the extract of Honda DREAMO strain contained in the sample contains an agonist of the μ1 opioid receptor, that is, it functions as an agonist of the μ1 opioid receptor.
Claims (5)
- 緑藻クラミドモナスまたは緑藻クラミドモナスの抽出物を含む組成物であって、
前記緑藻クラミドモナスまたは前記緑藻クラミドモナスの抽出物は、オピオイド受容体のアゴニストを含む、組成物。 A composition comprising the green alga Chlamydomonas reinhardtii or an extract of the green alga Chlamydomonas reinhardtii,
A composition, wherein the green alga Chlamydomonas or an extract of the green alga Chlamydomonas comprises an agonist of an opioid receptor. - 前記緑藻クラミドモナスは、Ｈｏｎｄａ ＤＲＥＡＭＯ株（受託番号ＦＥＲＭ ＢＰ－２２３０６）である、請求項１に記載の組成物。 The composition according to claim 1, wherein the green alga Chlamydomonas is the Honda DREAMO strain (accession number FERM BP-22306).
- 吐瀉薬、蠕動抑制薬または下痢症治療薬である、請求項１または２に記載の組成物。 The composition according to claim 1 or 2, which is an emetic, antiperistaltic or antidiarrheal drug.
- 前記オピオイド受容体は、μ１オピオイド受容体である、請求項１または２に記載の組成物。 The composition of claim 1 or 2, wherein the opioid receptor is the μ1 opioid receptor.
- 前記緑藻クラミドモナスは、淡水藻である、請求項１または２に記載の組成物。 The composition according to claim 1 or 2, wherein the green algae Chlamydomonas is a freshwater algae.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015189742A (en) * | 2014-03-28 | 2015-11-02 | 大阪瓦斯株式会社 | Ppar activity composition and energy production facility |
| WO2017217116A1 (en) * | 2016-06-17 | 2017-12-21 | 本田技研工業株式会社 | Novel microalga having aggregation ability |
| JP2020518659A (en) * | 2017-04-30 | 2020-06-25 | トリトン アルジー イノベーションズ | How to treat a condition of the digestive tract |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015189742A (en) * | 2014-03-28 | 2015-11-02 | 大阪瓦斯株式会社 | Ppar activity composition and energy production facility |
| WO2017217116A1 (en) * | 2016-06-17 | 2017-12-21 | 本田技研工業株式会社 | Novel microalga having aggregation ability |
| JP2020518659A (en) * | 2017-04-30 | 2020-06-25 | トリトン アルジー イノベーションズ | How to treat a condition of the digestive tract |
Non-Patent Citations (1)
| Title |
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| FIELDS FRANCIS J.; LEJZEROWICZ FRANCK; SCHROEDER DAVE; NGOI SOO M.; TRAN MILLER; MCDONALD DANIEL; JIANG LINGJING; CHANG JOHN T.; K: "Effects of the microalgae Chlamydomonas on gastrointestinal health", JOURNAL OF FUNCTIONAL FOODS, ELSEVIER BV, NL, vol. 65, 19 December 2019 (2019-12-19), NL , XP086004879, ISSN: 1756-4646, DOI: 10.1016/j.jff.2019.103738 * |
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