WO2022224644A1 - 馬乳酒由来エクソソーム及びその使用 - Google Patents
馬乳酒由来エクソソーム及びその使用 Download PDFInfo
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- WO2022224644A1 WO2022224644A1 PCT/JP2022/011880 JP2022011880W WO2022224644A1 WO 2022224644 A1 WO2022224644 A1 WO 2022224644A1 JP 2022011880 W JP2022011880 W JP 2022011880W WO 2022224644 A1 WO2022224644 A1 WO 2022224644A1
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- exosomes
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- lactic acid
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/20—Milk; Whey; Colostrum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
- A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
- A61K8/986—Milk; Derivatives thereof, e.g. butter
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/85—Products or compounds obtained by fermentation, e.g. yoghurt, beer, wine
Definitions
- the present invention relates to exosomes derived from horse milk and their uses.
- Exosomes are extracellular vesicles with a diameter of 30 to 200 nm (nanometers) secreted from cells, and are information molecules provided in cells, such as membrane proteins, intracellular proteins, nucleic acids (microRNA, messenger RNA, DNA, etc.). is incorporated and is considered to be responsible for information transmission between other cells (Non-Patent Document 1). In recent years, many attempts have been made to apply exosomes as pharmaceuticals, cosmetics, functional foods, and the like.
- Patent Document 1 describes pharmaceutical compositions comprising exosomes derived from mesenchymal stem cells and their use in methods of treating immune-mediated inflammatory diseases.
- An invention relating to is disclosed.
- Patent Document 2 discloses an invention relating to an anti-inflammatory agent containing milk-derived exosomes as an active ingredient.
- Patent Document 3 discloses an invention related to exosomes extracted from sake starter or moromi, or miso, and exosomes derived from yeast (starter, moromi, miso) are cell-killing factors secreted from NK cells. It is described that the expression level of granzyme is increased, and the gene expression level of collagen and elastin in aged fibroblasts is increased by the addition of yeast exosomes (Patent Document 3, paragraph 0055).
- TARC thymus and activation-regulated chemokine
- TRAC thymus and activation-regulated chemokine
- lymphocytes Th2 cells expressing CCR4
- IgE IgE production and eosinophils.
- Allergic symptoms are thought to occur due to the infiltration and activation of .
- Patent Document 4 discloses an invention relating to a human CCL17 antibody, and CCL17 (“CCL17” is another name for “TARC”) is used for ulcerative colitis, atopic dermatitis, and idiopathic lung disease.
- CCL17 is another name for “TARC”
- Human CCL17 antibodies have been described as useful for the treatment of such CCL17-mediated inflammatory diseases, as they are associated with human diseases affecting various organs, such as fibrosis and asthma ( Paragraphs 0004 and 0144 of Patent Document 4).
- TARC which is associated with the onset of various inflammatory diseases, can be suppressed, it would be promising as a therapeutic drug for those diseases.
- the antibody technology described in Patent Document 4 cannot be said to have practical versatility in terms of dosage form for patients and effect expression.
- an object of the present invention is to provide a new material that can inhibit TARC, which is associated with the onset of various inflammatory diseases, and that is useful, for example, in the treatment of atopic dermatitis.
- the present inventors have conducted various studies and found that horse lactic acid-derived exosomes have the effect of suppressing the production of TARC from normal human epidermal keratinocytes that induced an inflammatory reaction.
- the discovery led to the completion of the present invention.
- the present invention first provides a composition for skin treatment containing exosomes derived from horse milk.
- the present invention provides an anti-inflammatory composition containing exosomes derived from horse milk.
- the present invention provides a composition for suppressing TARC production containing exosomes derived from horse milk.
- the present invention provides a composition for treating atopic dermatitis containing exosomes derived from horse milk.
- the present invention provides a TARC production inhibitor containing exosomes derived from horse milk as an active ingredient.
- the present invention provides a composition for disease treatment containing the TARC production inhibitor.
- the disease is preferably a TARC-mediated disease. Moreover, it is preferable that the disease is atopic dermatitis.
- the present invention seventhly comprises a step of fractionating horse lactic acid into a plurality of fractions and a step of recovering exosome-enriched fractions from the plurality of fractions.
- Horse milk characterized by having It provides a method for producing a composition containing exosomes derived from sake.
- the present invention is obtained from horse lactic acid and provides a horse lactic acid-derived exosome-containing composition containing an exome-enriched fraction obtained by enriching the exosomes derived from the horse lactic acid. is.
- the horse lactic acid-derived exosomes provided by the present invention can suppress TARC, which is associated with the onset of various inflammatory diseases, and are useful, for example, in the treatment of atopic dermatitis. Moreover, it can be suitably used as a compounding component of a treatment composition to be administered to humans or animals.
- FIG. 1 (a) shows a graph of the particle size distribution
- FIG. 1 (b) An example of an observation field image is shown.
- Test Example 1 IL-10/TNF- ⁇ /IFN- ⁇ is applied to normal human epidermal keratinocytes to induce inflammation, and the expression level (relative value) of TARC produced at this time is given to horses.
- Test Example 1 IL-10 / TNF- ⁇ / IFN- ⁇ is applied to normal human epidermal keratinocytes to induce inflammation, and the expression level (relative value) of TSLP produced at this time is given to horses It is a chart showing the results of examining the effects of exosomes derived from milk.
- Test Example 1 IL-10 / TNF- ⁇ / IFN- ⁇ is applied to normal human epidermal keratinocytes to induce inflammation, and the expression level (relative value) of MDC produced at this time is given to horses It is a chart showing the results of examining the effects of exosomes derived from milk.
- horse milk liquor is synonymous with the meaning usually understood by those skilled in the art. It is a beverage that contains nutrients such as minerals and vitamins derived from it. It can be obtained by adding the rest of the prepared horse milk liquor to freshly squeezed horse milk and stirring. It is preferable to use horse milk liquor that originates from Mongolia.
- exosome is synonymous with the meaning usually understood by those skilled in the art, specifically, an extracellular vesicle with a diameter of 30 to 200 nm (nanometers) secreted from a cell, Membrane proteins, intracellular proteins, nucleic acids (microRNA, messenger RNA, DNA, etc.), etc., which are information molecules present in cells, are included.
- exosomes from horse milk for example, in order to remove protein components abundantly contained in horse milk, horse milk is treated with acetic acid to precipitate proteins, and the supernatant is subjected to ultracentrifugation. By separating, it is possible to obtain highly purified exosomes.
- Exosomes derived from horse lactic acid can be obtained, for example, through the following steps.
- (a) Subject horse milk liquor as a raw material to centrifugation or filter filtration to remove contaminants
- (b) Subject the sample from which contaminants have been removed through the above step (a) to ultracentrifugation
- (c) Collecting the precipitate from the treatment of step (b) above
- the centrifugal force conditions in the step (a) may be able to remove contaminants other than exosomes as a precipitate without precipitating exosomes, for example, 10,000 to 20,000 ⁇ g. , 10,000-17,000 ⁇ g, 12,000-17,000 ⁇ g, or 12,000-15,000 ⁇ g.
- the centrifugation time in step (a) may be, for example, 5 to 60 minutes, 10 to 45 minutes, or 15 to 30 minutes.
- the centrifugation temperature in the step (a) can be 4° C. to room temperature.
- Contaminants can be further removed from the supernatant obtained in the above step (a) by filter filtration (for example, filtration with a 0.65 ⁇ m filter), if necessary.
- the treatment of centrifugation or filter filtration may be carried out in two steps, if necessary.
- the order of the centrifugation process and the filter filtration process may be changed, or these processes may be alternately performed.
- exosomes may be collected in the precipitate, for example, may be 50,000 to 210,000 ⁇ g, at 70,000 to 200,000 ⁇ g may be between 70,000 and 200,000 ⁇ g, or between 100,000 and 180,000 ⁇ g.
- the centrifugation time in step (b) may be, for example, 50 minutes to 4 hours, 60 minutes to 4 hours, or 70 minutes to 4 hours.
- the centrifugation temperature in the step (b) can be 4° C. to room temperature.
- step (c) the supernatant obtained by the ultracentrifugation treatment in the step (b) is removed, and the precipitate obtained by the ultracentrifugation treatment in the step (b) is added with an appropriate solution such as phosphate buffered saline (PBS). Suspend in a suitable solvent and collect the precipitate. Collected exosomes, if necessary, can be washed with PBS or the like. Washing can be carried out by suspending the precipitate in PBS and then repeating ultracentrifugation under the conditions of step (b) above.
- PBS phosphate buffered saline
- step (a) the horse lactic acid as a raw material is subjected to centrifugation or filter filtration to the extent that exosomes are not removed, and contaminants are removed to the exosome fraction that is enriched in the later step. , the contaminants are prevented from being mixed.
- step (b) the exosomes floating in the horse milk are precipitated by ultracentrifugation, and the components other than the exosomes floating, dispersed, or dissolved in the horse milk are separated. can be done.
- the precipitated exosomes can be suspended in an appropriate solvent such as PBS and collected.
- exosomes contained in horse milk are selectively recovered and enriched.
- enrichment refers to the concentration in the prepared horse lactic acid-derived exosome-containing composition (e.g., the content of exosome components such as specific proteins, nucleic acids, lipids, etc. may be based on the number of may be), but preferably 2 times or more, 3 times or more, 4 times or more, 5 times or more, 6 times or more, 7 times or more, 8 times or more with respect to the concentration of exosomes contained in the raw horse milk liquor , 9 times or more, 10 times or more, 20 times or more, 30 times or more, 40 times or more, 50 times or more, 60 times or more, 70 times or more, 80 times or more, 90 times or more, 100 times or more, 200 times or more, 300 It means that it is increased by 1,000 times or more, 400 times or more, 500 times or more, 600 times or more, 700 times or more, 800 times or more, 900 times or more, or 1,000 times or more.
- the exosome-enriched fraction obtained contains the intended exosomes can be determined, for example, by measuring particles in the particle size range specific to exosomes, or by ELISA using an antibody that specifically recognizes exosomes. It can be confirmed by performing measurement or the like. Confirmation means are not limited to these, but particles in the particle size range peculiar to exosomes, for example, analyze the particle size based on the difference in the Brownian motion speed of individual particles, using a nanoparticle tracking analysis system can be measured. Specifically, a commercially available analysis system (trade name “Nanosign”, manufactured by Malvern Panalytical) can be used.
- ELISA measurement can be performed using an anti-exosome antibody that has cross-reactivity with animal species such as horses and cattle.
- an anti-exosome antibody that has cross-reactivity with animal species such as horses and cattle.
- a commercially available measurement kit “Milk Exosome ELISA Kit” manufactured by Cosmo Bio
- the average particle size of the horse lactic acid-derived exosomes provided by the present invention may be, for example, 80 to 200 nm, 100 to 180 nm, or 110 to 160 nm. Also, the peak diameter may preferably be 70 to 140 nm, 80 to 130 nm, or 90 to 120 nm.
- an exosome-enriched fraction is prepared from horse lactate and is intended to be used.
- a horse milk wine-derived exosome-containing composition containing an exome-enriched fraction.
- the step of fractionating horse lactic acid into multiple fractions and the step of recovering exosome-enriched fractions from the multiple fractions, a horse lactic acid-derived exosome-containing composition It is intended to provide a manufacturing method of.
- composition (agent) containing exosomes derived from horse milk As shown in the test examples described later, horse lactic acid-derived exosomes have the effect of suppressing the production of TARC produced by normal human epidermal keratinocytes that have induced an inflammatory reaction.
- the present invention provides various compositions to be used by applying horse milk-derived exosomes to humans or animals.
- Examples include the following compositions.
- (d) Composition for treating atopic dermatitis containing horse lactic acid-derived exosomes e
- TARC production inhibitor containing horse lactic acid-derived exosomes as an active ingredient
- compositions for skin treatment in addition to horse lactic acid-derived exosomes, pharmaceutically acceptable bases and carriers are added as necessary, and by conventional formulation methods, for example, creams, ointments, It can be in the form of lotions, gels, sprays, packs, patches, patches, liniments and the like, and can be in the form of compositions used for the purpose of applying and treating the skin.
- the anti-inflammatory composition can be a composition used for the purpose of preventing, ameliorating, treating, etc. symptoms of inflammation.
- the dosage form and dosage form may be the same as the above skin treatment composition, or any of oral, intravenous, intraperitoneal, transdermal, pulmonary, nasal, oral, enteral, etc. It can also be a dosage form. In this case, it may be in a form prepared to contain horse milk wine-derived exosomes by conventional formulation means together with an appropriately suitable pharmaceutical base, etc., so as to be suitable for the various dosage forms.
- it may be in the form of tablets, powders, liquids, powders, granules, soft capsules, hard capsules, jellies, troches, orally disintegrating agents, injections, inhalants, suppositories, liniments and the like.
- the composition for suppressing TARC production can be a composition used for the purpose of suppressing TARC production in desired cells.
- the dosage form or dosage form there are no particular restrictions on the dosage form or dosage form, and they may be the same as those for the above skin treatment composition and anti-inflammatory composition.
- a composition for treating atopic dermatitis can be a composition used for the purpose of preventing, ameliorating, or treating symptoms of atopic dermatitis.
- the dosage form or dosage form there are no particular restrictions on the dosage form or dosage form, and they may be the same as those for the above skin treatment composition and anti-inflammatory composition.
- it is preferably in the form used for the purpose of applying to the skin of the affected area of atopic dermatitis for treatment.
- the equine lactic acid-derived exosomes provided by the present invention can be a TARC production inhibitor as a drug substance used for the purpose of suppressing TARC production in desired cells. That is, it can be a TARC production inhibitor containing horse lactic acid-derived exosomes as an active ingredient.
- the TARC production inhibitor containing the horse lactic acid-derived exosomes as an active ingredient is a composition used for the purpose of preventing, improving, or treating the symptoms of TARC-mediated diseases. be able to.
- the dosage form or dosage form there are no particular restrictions on the dosage form, and they may be the same as those for the above skin treatment composition and anti-inflammatory composition.
- TARC-mediated disease refers to a disease in which TARC is involved in the disease, such as atopic dermatitis, but also contact dermatitis, nummular eczema, , stasis dermatitis, pompholyx, allergic contact dermatitis, folliculitis, psoriasis, itching from dry skin, urticaria, sebaceous eczema, seborrheic eczema, dyshidrotic eczema, nummular eczema , alopecia areata, hay fever, asthma, and animal allergies. Furthermore, for animals such as dogs and cats, there are tick- and flea-borne skin diseases.
- the content of exosomes contained in the composition is, in terms of mass of the exosome-enriched fraction prepared, for example, 1 to 100% by mass, 2 to 100 % by mass, 3 to 100% by mass, 4 to 100% by mass, 5 to 100% by mass, 10 to 100% by mass, 20 to 100% by mass, 30 to 100% by mass, 40 to 100% by mass, or 50 to 100% by mass %.
- number of exosomes for example, 4 ⁇ 10 8 to 1 ⁇ 10 14 /mL, 5 ⁇ 10 8 to 1 ⁇ 10 14 /mL, 1 ⁇ 10 9 to 1 ⁇ 10 14 /mL , 1 ⁇ 10 10 to 1 ⁇ 10 14 cells/mL, 1 ⁇ 10 11 to 1 ⁇ 10 14 cells/mL, or 1 ⁇ 10 12 to 1 ⁇ 10 14 cells/mL.
- 4 ⁇ 10 8 exosomes in terms of the number it usually corresponds to about 20 ⁇ g in terms of mass.
- the dosage of the exosomes can be appropriately set according to the form and purpose of the composition for using it.
- adults can ingest 0.001 mg to 10 g in terms of mass of the prepared exosome-enriched fraction per time, for example.
- the number of exosomes for example, 2 ⁇ 10 7 to 2 ⁇ 10 12 can be ingested.
- mass conversion of the prepared exosome-enriched fraction for example, 0.0001 mg ⁇ 0.1 g / cm 2 can be applied.
- 2 ⁇ 10 6 to 2 ⁇ 10 10 /cm 2 can be applied.
- compositions containing horse lactic acid-derived exosomes provided by the present invention may be used for the purpose of prevention, improvement, treatment, etc. of specific symptoms, or may be applied to healthy humans or animals good too. For example, it may be used to maintain healthy human or animal health.
- Compositions containing horse lactic acid-derived exosomes provided by the present invention are typically, for example, pharmaceuticals, quasi-drugs, functional foods, dietary supplements, supplements, health foods, veterinary drugs, animals It can be used in various product forms such as quasi-drugs for animals, functional foods for animals, nutritional supplements for animals, supplements for animals, health foods for animals, feeds, and feed additives. Or it can be used in combination with those products. Moreover, you may use it in combination with various foods and drinks.
- the present invention provides a method of treating a human or an animal by administering exosomes derived from horse milk.
- exosomes derived from horse milk For example, the following methods are mentioned.
- (a1) a method for treating skin by administering exosomes derived from horse lactic acid to humans or animals
- b1 a method for treating inflammation by administering exosomes derived from horse lactic acid to humans or animals
- (c1) exosomes derived from horse lactic acid to humans or animals TARC production suppression administered to, TSLP production suppression, or treatment method for MDC production suppression
- d1 treatment method for atopic dermatitis administering exosomes derived from horse lactic acid to humans or animals e1 exosomes derived from horse lactic acid to humans or animals.
- the present invention also provides the use of horse lactic acid-derived exosomes for administration and treatment of humans or animals.
- Examples include the following uses.
- (a2) Use of exosomes derived from horse lactic acid for treatment of skin (b2) Use of exosomes derived from horse lactic acid for treatment of inflammation (c2) Exosomes derived from horse lactic acid, TARC production suppression, TSLP production Use for suppression, or suppression of MDC production (d2) Use of malt-derived exosomes for treatment of atopic dermatitis (e2) Use of malt-derived exosomes for treatment of TARC-mediated diseases
- the cells were sown in a new culture vessel at a cell concentration of 40% confluency, and after culturing for 48 hours, the cells were sown in a 6-well plate at a cell concentration of 80% confluency.
- IL-10 was added to a final concentration of 10 ng/mL
- TNF- ⁇ to a final concentration of 10 ng/mL
- IFN- ⁇ to a final concentration of 10 ng/mL.
- the exosomes derived from horse lactic acid were added to the culture solution after culturing for 24 hours so that the final concentration was 2 ⁇ g/mL or 10 ⁇ g/mL.
- TARC thymus and activation-regulated chemokine
- TSLP thymic stromal lymphopoietin
- MDC macropage derived chemokine
- TARC is known as one of the chemokines that exhibit chemotaxis and the like for leukocyte cells and is known to be deeply involved in the onset of atopic dermatitis. It is known to be a master molecule involved in the establishment of allergic inflammation in general by participating in selective differentiation induction of cells (type 2 helper T cells) and maintenance of their functions.
- MDC also known as CCL22
- TARC is one of the chemokines that exhibit chemotaxis to leukocytic cells, and appears in the serum of patients with atopic dermatitis, reflecting its severity. It is known to be a molecule that
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Abstract
Description
えて攪拌を行うことなどによって得ることができる。馬乳酒は、モンゴル国を原産国にするものを用いることが好ましい。
馬乳酒に由来するエクソソームは、例えば、以下の工程を経ることにより得ることができる。
(a)原料とする馬乳酒を遠心ないしフィルターろ過の処理に供して夾雑物を除去する
(b)上記工程(a)を経て夾雑物を除去した試料を超遠心の処理に供する
(c)上記工程(b)の処理による沈殿物を回収する
後述する試験例に示されるように、馬乳酒由来エクソソームによれば、炎症反応を惹起した正常ヒト表皮角化細胞が産生するTARCの産生を抑制する作用効果がある。
(a)馬乳酒由来エクソソームを含有する皮膚処置用組成物
(b)馬乳酒由来エクソソームを含有する抗炎症用組成物
(c)馬乳酒由来エクソソームを含有するTARC産生抑制用組成物
(d)馬乳酒由来エクソソームを含有するアトピー性皮膚炎処置用組成物
(e)馬乳酒由来エクソソームを有効成分とするTARC産生抑制剤
(f)馬乳酒由来エクソソームを有効成分とするTARC産生抑制剤を含有する疾患処置
用組成物
(a1)馬乳酒由来エクソソームをヒト又は動物に投与する皮膚に対する処置方法
(b1)馬乳酒由来エクソソームをヒト又は動物に投与する炎症に対する処置方法
(c1)馬乳酒由来エクソソームをヒト又は動物に投与するTARC産生抑制、TSLP産生抑制、又はMDC産生抑制のための処置方法
(d1)馬乳酒由来エクソソームをヒト又は動物に投与するアトピー性皮膚炎に対する処置方法
(e1)馬乳酒由来エクソソームをヒト又は動物に投与するTARC媒介性疾患に対する処置方法
(a2)馬乳酒由来エクソソームの、皮膚に対する処置のための使用
(b2)馬乳酒由来エクソソームの、炎症に対する処置のための使用
(c2)馬乳酒由来エクソソームの、TARC産生抑制、TSLP産生抑制、又はMDC産生抑制のための使用
(d2)馬乳酒由来エクソソームの、アトピー性皮膚炎に対する処置のための使用
(e2)馬乳酒由来エクソソームの、TARC媒介性疾患に対する処置のための使用
馬乳酒(原産国:モンゴル国)を準備し、その50mLを低速遠心(2000×g、5分)にかけて細胞破砕物等の夾雑物を除去した。次いで、37℃に保温しつつ500μLの酢酸溶液を加えて転倒混和したのち、遠心機(12,000×g、10分、4℃)にかけて、その上清を新しいチューブに回収した。これを超遠心装置(ベックマン社製、100,000×g、70分、4℃)にかけて、その沈降画分を回収した。沈渣はPBS(-)に分散させ、同様の超遠心を繰り返し、洗浄、夾雑タンパク質を除去した。最終的にこれをPBS(-)に懸濁させて、以下の試験に用いた。
正常ヒト表皮角化細胞(商品名「正常ヒト表皮角化細胞(成人、単一ドナー):Normal Human Epidermal Keratinocytes (NHEK), adult donor, single donor」、PromoCell社製)を、常法に従い、ケラチノサイト専用培地(商品名「角化細胞増殖培地2キット:Keratinocyte Growth Medium 2 Kit」、PromoCell社製)を用いて、5%CO2、37℃下に75cm2の平底プレート培養容器でサブコンフルエントになるまで培養した。継代のため、新たな培養容器に40%コンフルエントの細胞濃度となるよう播種した後、更に、48時間培養後、6-ウエルプレートに80%コンフルエントの細胞濃度で播種した。24時間培養後、IL-10を終濃度10ng/mLとなるように、TNF-αを終濃度10ng/mLとなるように、IFN-γを終濃度10ng/mLとなるように、それぞれを添加し、更に、24時間培養した。そして、その24時間培養後の培養液に、馬乳酒由来エクソソームを終濃度2μg/mL又は10μg/mLとなるように添加した。
Claims (10)
- 馬乳酒由来エクソソームを含有する皮膚処置用組成物。
- 馬乳酒由来エクソソームを含有する抗炎症用組成物。
- 馬乳酒由来エクソソームを含有するTARC産生抑制用組成物。
- 馬乳酒由来エクソソームを含有するアトピー性皮膚炎処置用組成物。
- 馬乳酒由来エクソソームを有効成分とするTARC産生抑制剤。
- 請求項5記載のTARC産生抑制剤を含有する疾患処置用組成物。
- 前記疾患がTARC媒介性疾患である、請求項6記載の組成物。
- 前記疾患がアトピー性皮膚炎である、請求項6記載の組成物。
- 馬乳酒を複数画分に分画する工程と、前記複数画分からエクソソームが富化された画分を回収する工程とを有することを特徴とする馬乳酒由来エクソソーム含有組成物の製造方法。
- 馬乳酒から得られ、前記馬乳酒に由来するエクソソームを富化してなるエクソーム富化画分を含有する馬乳酒由来エクソソーム含有組成物。
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JP2016056119A (ja) * | 2014-09-09 | 2016-04-21 | 森永乳業株式会社 | アポトーシス抑制剤 |
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JP2016056119A (ja) * | 2014-09-09 | 2016-04-21 | 森永乳業株式会社 | アポトーシス抑制剤 |
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