KR101686064B1 - Composition for immunosuppression and anti-inflammation - Google Patents
Composition for immunosuppression and anti-inflammation Download PDFInfo
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- KR101686064B1 KR101686064B1 KR1020150133375A KR20150133375A KR101686064B1 KR 101686064 B1 KR101686064 B1 KR 101686064B1 KR 1020150133375 A KR1020150133375 A KR 1020150133375A KR 20150133375 A KR20150133375 A KR 20150133375A KR 101686064 B1 KR101686064 B1 KR 101686064B1
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- inflammatory
- immune
- exosome
- concentrated filtrate
- disease
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Abstract
The present invention relates to a composition capable of treating or preventing immune or inflammation-related diseases by inhibiting the activity or proliferation of immune cells using clotted blood.
Description
The present invention relates to a composition capable of treating or preventing immune or inflammation-related diseases by inhibiting the activity and proliferation of immune cells using clotted blood.
Recently, acute inflammatory diseases and chronic inflammatory diseases such as rheumatoid arthritis, herpes zoster, and rhinitis have been increasing due to changes in aging and dietary habits (Hyun EA, Anti-inflammatory effect of Salvia officinalis L. extract.Cheju National University. Korea 2003 .). As chronic inflammation has been reported to correlate with cancer or other diseases, efforts have been made to reduce the risk of disease by using dietary interventions to reduce the inflammatory response (Aggarwal BB et al. Inflammation and can cer : How hot is the link 72: 1605-1621 (2006)).
Inflammatory responses are one of defense mechanisms against biopsies against physical, chemical stimuli or bacterial infections from the outside and are the mechanism to repair or regenerate injured tissues (Zamora R, et al., Inducible nitric oxide synthase and inflammatory diseases. 6: 347-373 (2000)). When inflammation occurs in the body, inflammatory cells such as macrophages secrete NO, prostaglandin E 2 (PGE 2 ), tumor necrosis factor-α, TNF-α, interleukin-1β (IL- (Guha M, Mackman N. LPS induction of gene expression in human monocytes, Cell Signal. 13: 85-94 (2001)).
In particular, activation of the nuclear factor-kB (nuclear factor-kB, NF-kB), which is a transcription factor of the inflammatory response, by stimulation such as cytokine, TNF-α and lipopolysaccharide (NO) and prostaglandin E 2 (PGE 2 ) by expressing inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX- 2 ) (Nishida T et al., Geranylgeranylacetone induces cyclooxygenase-2 expression in cultured rat gastric epithelial cells through NF-kappa B. Digestive Diseases and Sciences. 52: 1890-1896 (2007)).
The synthetic anti-inflammatory drugs developed so far are largely classified into steroids (hydrocortisone, prednisolone, betamethasone) and non-steroids (aspirin, indomethacin and ibuprofen), most of which show side effects such as gastrointestinal, kidney and heart disease (2006) and Makins R, Ballinger A. Gastrointestinal side effects of drugs. Expert Opin Drug Saf. 2: 421-429 (2003) )) It is necessary to develop anti-inflammatory drugs derived from natural products that are safer and more effective.
The present invention provides a composition capable of treating or preventing immune or inflammation-related diseases by inhibiting the activity and proliferation of immune cells safely and effectively, and a method for producing the same.
The inventors of the present invention inhibited the proliferation of immune cells when the bovine clotted blood, that is, the blood cells were treated with immune cells, and suppressed the expression of signal molecules mediating the inflammatory response by being secreted from the immune cells And came to the present invention.
According to one embodiment of the present invention, there is provided a pharmaceutical composition for treating or preventing an immunological or inflammatory disease comprising bovine blood clot as an active ingredient.
Herein, the bovine bovine blood itself may be used. Preferably, however, the bovine blood clot can be used, but it is preferable to use the pulverized product of bovine blood or the concentrated filtrate obtained by filtering the pulverized product, or the supernatant obtained by centrifuging the concentrated filtrate, A supernatant obtained by a Ficoll-concentration gradient can be used.
In the present invention, the bovine blood clot includes an exosome having immunosuppressive and anti-inflammatory properties. Accordingly, the pharmaceutical composition of the present invention may contain an exosome isolated from bovine blood clusters in order to secure an excellent immunosuppressive and anti-inflammatory effect while preventing an unexpected additional effect. Here, it is preferable that the exosome has a size (diameter) of 30 to 1,000 nm, because it can further improve immunosuppressive and anti-inflammatory effects.
According to another embodiment of the present invention, there is provided a pharmaceutical composition for treating or preventing an immunological or inflammatory disease comprising, as an active ingredient, exosomes isolated from bovine blood.
In the present invention, the exosome may be obtained by pulverizing bovine blood or bovine blood, or a concentrated filtrate obtained by filtering the pulverized product, or a supernatant obtained by centrifuging the concentrated filtrate, or a supernatant obtained by centrifuging the concentrated filtrate, , ≪ / RTI >
In addition, in the present invention, it is preferable that the exosome has a size (diameter) of 30 to 1,000 nm because it can further improve immunosuppressive and anti-inflammatory effects.
The method of isolating the exosome according to the present invention is not particularly limited. For example, salting-out method is preferable because it can effectively isolate exosomes having immunosuppressive and anti-inflammatory properties .
As the salting-out method, 1 M sodium acetate was added to the mixed culture until the final concentration reached 0.05-0.2 M, the exosomes were condensed by the charge difference, and then centrifuged at 4,000-6,000 g to separate .
According to another embodiment of the present invention, there is provided a method for preparing a bovine blood clot; And pulverizing the bovine blood clot. The present invention also provides a method for producing a pharmaceutical composition for treating or preventing an immune or inflammatory disease.
In the present invention, the pulverization conditions are not particularly limited, but may be pulverized at 500 to 1,000 rpm for 5 to 10 minutes using a mixed homogenizer.
The present invention can further carry out a step of obtaining a concentrated filtrate by filtering the obtained pulverized product subsequently to the pulverizing step. The type of the filter used for the filtration is not particularly limited, and for example, a 45-400 mesh filter may be used.
In the present invention, if necessary, centrifuging the concentrated filtrate as described above under a condition of 200 to 4,000 rpm, preferably 1,000 to 4,000 rpm to obtain a supernatant may be further carried out, or a concentrate filtrate Filtration step can be additionally carried out. Further, a step of filtering the obtained separated product with a 0.1 to 0.5 mu m filter, preferably a 0.22 to 0.45 mu m filter can be further carried out .
In addition, in the present invention, in order to prevent an unexpected additional effect while ensuring excellent immunosuppressive and anti-inflammatory effects, it is possible to carry out the step of isolating exosome from the crushed or pulverized filtrate of bovine blood clotted as described above have.
At this time, the method for separating exosome is not particularly limited. For example, salting-out method is preferable because exosome having immunosuppressive and anti-inflammatory properties can be effectively separated.
As the salting-out method, 1 M sodium acetate was added to the mixed culture until the final concentration reached 0.05-0.2 M, the exosomes were condensed by the charge difference, and then centrifuged at 4,000-6,000 g to separate .
However, in the present invention, the term "blood clot" means a mass of dark red color formed by loss of fluidity and solidification when the blood is left standing. As shown in Fig. 1, platelet rich plasma (platelet) containing a large amount of blood cells such as red blood cells and white blood cells and platelets Rich Plasma, PRP), and may also contain minor amounts of serum components.
The term "exosome " in the present invention means a small vesicle of membrane structure secreted from various cells. The diameter of the exosome is approximately 30 to 1,000 nm, which means the follicle that is fused to the plasma membrane and released to the extracellular environment. Representative expression markers of exosomes correspond to HSP70, CD63 and CD9.
In the composition of the present invention, the immune disease may be any disease caused by the activation of T cells, and specifically, it is characterized by autoimmune disease or transplant rejection of organ or tissue.
In the present invention, the term " autoimmune disease " refers to a disease in which immune cells responding to host tissues and endothelial magnetic peptides are induced, resulting in abnormalities in the system controlling the autoimmune response. Refers to diseases caused by activation of T cells that respond to autoantigens. T cells or B cells are randomly differentiated to have various specificities. In this process, cells that can be specifically activated by autoantigens can be generated, which is called self-recognition. In order to prevent the self-recognition, immune tolerance exists in the immune system of the human body. When immune tolerance fails in the body and immune cells that recognize self-activation are activated, autoimmune disease occurs. Autoimmune diseases are caused by genetic factors (inappropriate MHC expression), internal / external antigens, cytokine modulation disorders, destruction of immunosuppressive function, or organ defects.
The "organ or tissue transplant rejection" of the present invention is a disease caused by a cell mediated immune response. The human body has a complex defense mechanism against external substances such as bacteria or viruses that invade the body. This mechanism of the immune system is indistinguishable from disease-causing microorganisms and life-saving graft cells, both of which are regarded as foreign substances and are attacked by the immune system, leading to graft rejection. The T cell mediated response is initiated when the recipient's lymphocyte meets the MHC of the donor. In other words, when the host T cell meets the bifurcated cells in the transplant organs or the donor bifurcation enters the recipient's lymph node, the immune function begins. The activated CD4 T cells secrete cytokines that appear in the delayed hypersensitivity reaction, And causes local infiltration of mononuclear cells such as lymphocytes and macrophages. Microvilli damage, tissue ischemia and graft destruction are caused by infiltrated macrophages. However, if T lymphocytes cause inflammation and damage to the graft over several days to several months, the graft may be safe if such a cell mediated reaction is suppressed.
In the present invention, the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, diabetes, atopic dermatitis, alopecia areata, psoriasis, pemphigus, asthma, aphthas stomatitis, chronic thyroiditis, ulcerative colitis, Scleroderma, autoimmune hemolytic anemia, autoimmune encephalomyelitis, fibromyalgia, temporal arteritis and the like.
The term " inflammatory disease " as used herein refers to any disease or condition that can be treated or treated, including, but not limited to, venous sinusitis, gastritis, rhinitis, conjunctivitis, asthma, bronchitis, dermatitis, atopic dermatitis, inflammatory growth diseases, inflammatory liver diseases, inflammatory vascular diseases, inflammatory rheumatoid arthritis, Psoriasis, multiple sclerosis and inflammatory lung disease.
Among the immunological diseases or inflammatory diseases of the present invention, "atopic dermatitis" is a representative skin disease occurring in a person having atopic allergy. Often, it is a chronic skin disease called as fever, and dry skin and itching are the main symptoms. It has immunologic characteristics and it is accompanied by other allergic diseases such as urticaria, metal allergy, asthma or allergic rhinitis, and it tends to have a family history. Symptoms usually appear at 2 to 6 months of age, especially at 1 year of age and 85% at age 5. It is usually known to be a short-lived disease at a young age, but 50% of the patients disappear within two months, 25% appear until adolescence, and the remaining 25% continue to disappear even as adults. Unbearable itching can distract attention, interfere with learning, cause sexual degradation, and can lead to damage or emotional hurt by other children's teasing or bullying.
In the present invention, the pharmaceutical composition may further comprise an appropriate carrier, excipient or diluent according to a conventional method. Examples of carriers, excipients and diluents that can be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium But are not limited to, silicates, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
The pharmaceutical composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, external preparations, suppositories or sterilized injection solutions, Can be used. In detail, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant and the like which are usually used. The solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like. These solid preparations can be prepared by mixing at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like, and various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. in addition to commonly used diluents such as water and liquid paraffin . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.
The route of administration of the pharmaceutical composition according to the present invention may be, but is not limited to, oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, , Sublingual or rectal. Oral or parenteral administration is preferred. The term "parenteral" as used herein includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques. The pharmaceutical compositions of the present invention may also be administered in the form of suppositories for rectal administration.
The pharmaceutical composition of the present invention may be administered orally or parenterally depending on various factors including the activity of the specific compound used, age, weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination, And the dosage of the pharmaceutical composition may be appropriately selected by a person skilled in the art depending on the condition of the patient, the body weight, the degree of disease, the type of drug, the route of administration and the period of time, and is preferably from 0.0001 to 50 mg / kg or 0.001 to 50 mg / kg. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way. The pharmaceutical compositions according to the present invention can be formulated into pills, dragees, capsules, solutions, gels, syrups, slurries, suspensions.
According to another embodiment of the present invention, it can be used as a food composition for improving immunological or inflammatory diseases, which comprises bovine blood clot as an active ingredient.
In the present invention, the bovine blood clot includes an exosome having immunosuppressive and anti-inflammatory properties. Accordingly, the food composition of the present invention may contain an exosome isolated from bovine blood clusters in order to ensure an excellent immunosuppressive and anti-inflammatory effect while preventing the occurrence of unexpected additional effects. Here, it is preferable that the exosome has a size (diameter) of 30 to 1,000 nm, because it can further improve immunosuppressive and anti-inflammatory effects.
In the present invention, the method for separating exosome from the bovine blood clot is not particularly limited. For example, by salting out, exosomes having immunosuppressive and anti-inflammatory properties can be effectively separated, Do.
As the salting-out method, 1 M sodium acetate was added to the mixed culture until the final concentration reached 0.05-0.2 M, the exosomes were condensed by the charge difference, and then centrifuged at 4,000-6,000 g to separate .
The food composition containing the bovine blood clot as an active ingredient of the present invention can be prepared in the form of various foods such as beverage, gum, tea, vitamin complex, powder, granule, tablet, capsule, have. Since the food composition of the present invention is composed of a plant extract having little toxicity and side effects, it can be safely used for prolonged use even for prophylactic purposes.
When the bovine blood clot of the present invention is contained in the food composition, the amount thereof may be added in a proportion of 0.1 to 50% of the total weight.
Here, when the food composition is prepared in a beverage form, there are no particular limitations other than those containing the food composition at the indicated ratios and may contain various flavors or natural carbohydrates such as ordinary beverages as an additional ingredient. That is, natural carbohydrates include monosaccharides such as glucose, disaccharides such as fructose, sucrose and the like and sugar sugars such as polysaccharide, dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol can do. Examples of the above-mentioned flavors include natural flavors (such as tau martin and stevia extract (for example, rebaudioside A and glycyrrhizin) and synthetic flavors (for example, saccharine and aspartame).
In addition, the food composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants, pectic acid and its salts, alginic acid and its salts, , a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, a carbonating agent used in a carbonated drink, and the like.
These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of about 0.1 to 50 parts by weight per 100 parts by weight of the composition of the present invention.
According to another embodiment of the present invention, it can be used as a cosmetic composition for improving immunological or inflammatory diseases, which comprises bovine blood.
In the present invention, the bovine blood clot includes an exosome having immunosuppressive and anti-inflammatory properties. Accordingly, the cosmetic composition of the present invention may contain an exosome isolated from bovine blood clots in order to secure an excellent immunosuppressive and anti-inflammatory effect while preventing an unexpected additional effect. Here, it is preferable that the exosome has a size (diameter) of 30 to 1,000 nm, because it can further improve immunosuppressive and anti-inflammatory effects.
In the present invention, the method for separating exosome from the bovine blood clot is not particularly limited. For example, by salting out, exosomes having immunosuppressive and anti-inflammatory properties can be effectively separated, Do.
As the salting-out method, 1 M sodium acetate was added to the mixed culture until the final concentration reached 0.05-0.2 M, the exosomes were condensed by the charge difference, and then centrifuged at 4,000-6,000 g to separate .
In the present invention, it is preferable that the exosome has a size of 30-1,000 nm because it can further improve the immunosuppressive and anti-inflammatory effects.
The cosmetic composition comprising the composition of the present invention as an active ingredient can be used as a skin lotion, a nutritional lotion, a nutrition essence, a massage cream, a cosmetic bath additive, a body lotion, a body milk, a bath oil, a baby oil, Skin lotions, skin creams, sunscreen cosmetics, cleansing milks, hair removal products, cosmetics, face and body lotions, face and body creams, skin whitening creams, hand lotions, hair lotions, Soap, facial wash, whole body cleanser, scalp cleanser, hair rinse, cosmetic soap, toothpaste, cosmetic cream, jasmine oil, bath soap, water soap, beauty soap, shampoo, hand cleanser Bleaching gel, toothpaste, and the like. To this end, the composition of the present invention may further comprise a solvent commonly used in the production of a cosmetic composition, or a suitable carrier, excipient or diluent.
For example, water, saline solution, DMSO, or a combination thereof may be used. Examples of the carrier, excipient or diluent include purified water, oil, wax But are not limited to, fatty acids, fatty acid alcohols, fatty acid esters, surfactants, humectants, thickeners, antioxidants, viscosity stabilizers, chelating agents, buffers, lower alcohols and the like. Further, if necessary, it may contain a whitening agent, a moisturizing agent, a vitamin, an ultraviolet screening agent, a perfume, a dye, an antibiotic, an antibacterial agent, and an antifungal agent.
As the oil, hydrogenated vegetable oil, castor oil, cottonseed oil, olive oil, palm oil, jojoba oil and avocado oil may be used. Examples of the wax include wax, wax, carnauba, candelilla, montan, ceresin, liquid paraffin, Can be used.
As the fatty acid, stearic acid, linoleic acid, linolenic acid and oleic acid may be used. As fatty alcohol, cetyl alcohol, octyldodecanol, oleyl alcohol, panthenol, lanolin alcohol, stearyl alcohol and hexadecanol may be used As the fatty acid ester, isopropyl myristate, isopropyl palmitate, and butyl stearate may be used. As the surfactant, a cationic surfactant, an anionic surfactant and a nonionic surfactant known in the art can be used, and a surfactant derived from a natural material is preferably used.
In addition, it may contain a hygroscopic agent, a thickening agent, an antioxidant and the like widely known in the field of cosmetics, and the kind and amount thereof are well known in the art.
The use of the bovine bovine according to the present invention can safely and effectively inhibit the proliferation of immune cells. By secretion from the immune cells, it is possible to inhibit the expression of signal molecules mediating the inflammatory response and treat or prevent immune or inflammatory diseases Can be prevented.
1 schematically shows a schematic diagram of a blood clot used in the present invention.
FIG. 2 is a graph comparing cell numbers of RBL-2H3 macrophages according to each treatment in Example 1. FIG.
FIG. 3 is a graph comparing the expression levels of TNF-a, IL-1b, IL-6 and IL-4 genes in RBL-2H3 macrophages according to each treatment in Example 2. FIG.
Fig. 4 is a graph comparing the degree of expression of TNF-a and IL-6 in RBL-2H3 macrophages according to each treatment in Example 3. Fig.
Hereinafter, preferred embodiments of the present invention will be described. However, the embodiments of the present invention can be modified into various other forms, and the scope of the present invention is not limited to the embodiments described below. Further, the embodiments of the present invention are provided to more fully explain the present invention to those skilled in the art.
Example
[Example 1] Confirmation of proliferation inhibitory effect of immune cells
Bovine blood clots were pulverized for 10 minutes at 500-1,000 rpm using a homogenizer and then passed through a mesh filter to obtain a concentrated fraction. The resulting concentrated filtrate was treated with 1 M sodium acetate to a final concentration of 0.1 M, allowed to stand at 4 ° C for 45 minutes, allowed to stand at 37 ° C for 5 minutes, and then centrifuged at 4,000 g for 10 minutes to obtain a clot exo And the exosomes isolated as described above were added to the nutrient medium (DMEM / F12 media) supplemented with 10% FBS in an amount of 10% by weight and 20% by weight.
As a positive control, exosomes (WB exo) were separated from the blood of cows before solidification, that is, whole blood in the same manner as described above, and serum was separated from the whole blood, , And each of them was added to a nutrient medium (DMEM / F12 media) supplemented with 10% FBS to give an amount of 10% by weight and 20% by weight. As a negative control, nutrient medium (DMEM / F12 media) supplemented with 10% FBS was prepared.
Thereafter, RBL-2H3, a rat-derived macrophage, was inoculated at 5,000 cfu in each of the prepared cultures, and the number of cells was measured. The results are shown in FIG.
As shown in FIG. 2, when the exosomes isolated from bovine blood clots were treated, the exosomes or the serum isolated from whole blood were treated, or when cultured in a culture medium containing 10% FBS without any treatment It can be seen that the effect of inhibiting the proliferation of macrophages is excellent.
[Example 2] Confirmation of anti-inflammatory effect
Blood clots were pulverized using a homogenizer at 500 to 1,000 rpm for 10 minutes and then passed through a mesh filter to obtain concentrated fractions. Then, 1 M sodium acetate was added to a final concentration of 0.1 M, After allowing to stand at 37 ° C for 5 minutes, exosomes (clot EX) were separated by centrifugation at 4,000 g for 10 minutes. The clot thus obtained was then added to the nutrient medium (DMEM / F12 media) in an amount of 10% by weight and the exosomes (clot EX) were added in an amount of 10% by weight and 20% by weight To the nutrient medium (DMEM / F12 media).
On the other hand, RBL-2H3 cells, which are macrophages derived from rats, were treated with LPS (Lipopolysaccharide) for 24 hours to induce inflammation. The cells were inoculated into the culture solution at 30,000 cfu and RT- -a, IL-1b, IL-6, and IL-4 were compared with each other in a graph of FIG. The expression level of TNF-a, IL-1b, IL-6 and IL-4 genes in RBL-2H3 cells (LPS) treated with LPS and RBL-2H3 cells Were compared.
As shown in FIG. 3, when macrophages were treated with LPS, the expression of TNF-a, IL-1b, IL-6 and IL-4 genes as inflammation related genes was increased. However, The expression of these genes was markedly reduced in the case of treatment with the exosome.
[Example 3] Confirmation of anti-inflammatory effect
Each of the concentrated filtrate obtained from bovine blood clots and the exosome isolated therefrom was added to a nutrient medium (DMEM / F12 media) in an amount of 10% by weight as in Example 2 above.
On the other hand, RBL-2H3 cells, which are macrophages derived from rats, were treated with LPS (Lipopolysaccharide) for 24 hours to induce inflammation. Then, the cells were inoculated with 30,000 cfu in the culture medium, and TNF-a , IL-6, and IL-4, are graphically represented in FIG. As a control, the expression levels of TNF-a, IL-6 and IL-4 in RBL-2H3 cells (LPS) treated with LPS and RBL-2H3 cells (NC) without any treatment were compared.
As shown in FIG. 4, when macrophages were treated with LPS, expression of inflammatory genes TNF-a, IL-6 and IL-4 was increased. However, as in the present invention, The expression of these genes was markedly reduced by treatment with clot EX.
Thus, the bovine blood clots according to the present invention and further the exosomes isolated therefrom suppress the proliferation of immune cells, inhibit the expression of inflammatory cytokines produced by LPS, and have immunosuppressive and anti-inflammatory effects .
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is clearly understood that the same is by way of illustration and example only and is not to be taken by way of limitation, It is to be understood that the invention may be practiced within the scope of the appended claims.
Claims (20)
Wherein said bovine blood clot inhibits the expression of at least one of TNF-a, IL-1b, IL-6 and IL-4.
The bovine blood clot is a bovine blood clot; A concentrated filtrate obtained by filtering the pulverized product; A supernatant obtained by centrifuging the concentrated filtrate; Or a pharmaceutical composition for the treatment or prevention of an immunological or inflammatory disease, wherein the concentrated filtrate is a supernatant obtained by a Ficoll-concentration gradient.
The pharmaceutical composition for treating or preventing an immune or inflammatory disease, wherein said bovine blood clot comprises exosome.
Wherein the size of the exosome is from 30 to 1,000 nm, for the treatment or prevention of an immune or inflammatory disease.
The pharmaceutical composition for treating or preventing an immune or inflammatory disease, wherein the immune disease is an autoimmune disease or a graft rejection reaction of an organ or tissue.
Wherein said autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, diabetes, atopic dermatitis, alopecia areata, psoriasis, pemphigus, asthma, aphthas stomatitis, chronic thyroiditis, ulcerative colitis, multiple myositis, Anemia, autoimmune encephalomyelitis, fibromyalgia, and temporal arteritis. ≪ Desc / Clms Page number 24 >
The inflammatory disease is selected from the group consisting of venous sinusitis, gastritis, rhinitis, conjunctivitis, asthma, bronchitis, dermatitis, atopic dermatitis, inflammatory growth diseases, inflammatory liver diseases, inflammatory vascular diseases, inflammatory rheumatoid arthritis, restenosis, psoriasis, ≪ RTI ID = 0.0 > and / or < / RTI > disease.
Wherein said exosome inhibits the expression of at least one of TNF-a, IL-1b, IL-6 and IL-4.
Said exosome is a bovine blood vessel; A crushed product of said bovine blood clot; A concentrated filtrate obtained by filtering the pulverized product; A supernatant obtained by centrifuging the concentrated filtrate; Or the concentrated filtrate is separated from the supernatant obtained by the gradient of the phycol-concentration.
Wherein the size of the exosome is from 30 to 1,000 nm, for the treatment or prevention of an immune or inflammatory disease.
And crushing the bovine blood clot,
A method for the preparation of a pharmaceutical composition for treating or preventing an immunological or inflammatory disease, wherein the crushed bovine blood clot inhibits the expression of at least one of TNF-a, IL-1b, IL-6 and IL-4.
Wherein the pulverizing step is carried out at 500 to 1,000 rpm for 5 to 10 minutes using a mixed homogenizer for the treatment or prevention of an immune or inflammatory disease.
Wherein the step of pulverizing the bovine bovine is followed by filtration of the obtained pulverized product to obtain a concentrated filtrate. The method for producing a pharmaceutical composition for treating or preventing an immune or inflammatory disease, comprising the steps of:
Wherein said filtration is carried out using a 45-400 mesh filter.
The method for producing a pharmaceutical composition for the treatment or prevention of immune or inflammatory diseases according to claim 1, further comprising, after the step of obtaining the concentrated filtrate, further centrifuging the concentrated filtrate under a condition of 200 to 4,000 rpm to obtain a supernatant .
The step of separating the concentrated filtrate into a Pichol concentration-gradient, followed by filtration with a filter of 0.1 to 0.5 mu m, in the step of obtaining the concentrated filtrate, wherein the pharmaceutical composition for treating or preventing an immune or inflammatory disease Gt;
Further comprising the step of separating the exosome from the obtained pulverized product subsequently to the pulverizing step.
Wherein the step of isolating the exosome is a salting out method for the preparation of a pharmaceutical composition for the treatment or prevention of immune or inflammatory diseases.
Wherein said bovine blood clot inhibits the expression of at least one of TNF-a, IL-1b, IL-6 and IL-4.
Wherein said bovine blood clot inhibits the expression of at least one of TNF-a, IL-1b, IL-6 and IL-4.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018056481A1 (en) * | 2016-09-23 | 2018-03-29 | ㈜프로스테믹스 | Immunosuppression and antiinflammatory composition |
| KR20190003387A (en) * | 2017-06-30 | 2019-01-09 | 주식회사 엑소코바이오 | A composition comprising an exosome derived from stem cell as an active ingredient and its application for suppressing or improving pruritus |
| KR101964992B1 (en) * | 2018-06-02 | 2019-04-02 | 주식회사 엑소코바이오 | Cosmetic composition for moisturizing skin and improving pruritus |
| KR101964991B1 (en) * | 2017-12-10 | 2019-04-02 | 주식회사 엑소코바이오 | New use of exosome kit comprising exosomes derived from stem cells |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2018056481A1 (en) * | 2016-09-23 | 2018-03-29 | ㈜프로스테믹스 | Immunosuppression and antiinflammatory composition |
| KR20190003387A (en) * | 2017-06-30 | 2019-01-09 | 주식회사 엑소코바이오 | A composition comprising an exosome derived from stem cell as an active ingredient and its application for suppressing or improving pruritus |
| KR102147169B1 (en) | 2017-06-30 | 2020-08-24 | 주식회사 엑소코바이오 | A composition comprising an exosome derived from stem cell as an active ingredient and its application for suppressing or improving pruritus |
| EP3646877A4 (en) * | 2017-06-30 | 2021-05-26 | Exocobio Inc. | Use of composition comprising stem cell-derived exosome as effective ingredient for prevention or alleviation of pruritus |
| US11446333B2 (en) | 2017-06-30 | 2022-09-20 | Exocobio Inc. | Use of composition comprising stem cell-derived exosome as effective ingredient for suppression or alleviation of pruritus |
| KR20190049474A (en) * | 2017-10-31 | 2019-05-09 | 주식회사 엑소코바이오 | Exosome kit and method for improving transdermal delivery of exosomes using the same |
| KR102320845B1 (en) | 2017-10-31 | 2021-11-02 | 주식회사 엑소코바이오 | Exosome kit and method for improving transdermal delivery of exosomes using the same |
| KR101964991B1 (en) * | 2017-12-10 | 2019-04-02 | 주식회사 엑소코바이오 | New use of exosome kit comprising exosomes derived from stem cells |
| KR101964992B1 (en) * | 2018-06-02 | 2019-04-02 | 주식회사 엑소코바이오 | Cosmetic composition for moisturizing skin and improving pruritus |
| WO2019231050A1 (en) * | 2018-06-02 | 2019-12-05 | 주식회사 엑소코바이오 | Cosmetic composition for hydrating skin and alleviating pruritus |
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