WO2023119063A1 - Placental composition - Google Patents
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- WO2023119063A1 WO2023119063A1 PCT/IB2022/062160 IB2022062160W WO2023119063A1 WO 2023119063 A1 WO2023119063 A1 WO 2023119063A1 IB 2022062160 W IB2022062160 W IB 2022062160W WO 2023119063 A1 WO2023119063 A1 WO 2023119063A1
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Classifications
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- 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
- A61K35/48—Reproductive organs
- A61K35/50—Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
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- A—HUMAN NECESSITIES
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- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
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- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
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- A—HUMAN NECESSITIES
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- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/204—Animal extracts
Definitions
- the present invention relates to the use of placental extract and compositions comprising placenta extract to treat or prevent inflammation of a disease or condition associated with TNFa, IL-lbeta, IL-6 and other pro-inflammatory cytokines, such as asthma, infections, acute respiratory distress syndrome (ARDS), or COVID-19.
- the invention also relates to methods of treatment by administering placental extract and compositions comprising placenta extract, and the use of placenta extract in the manufacture of a medicament or composition for treating such diseases or conditions.
- pro-inflammatory cytokines Although the production of pro-inflammatory cytokines by cells of the innate immune system plays an important role in mediating the initial host defense against invading pathogens (O'Neill, L. A. et al., Immunol. Today, (2000), 21 (5):206-9), an inability to regulate the nature or duration of the host's inflammatory response can often mediate detrimental host effects as observed in chronic inflammatory diseases. Additionally, in the early stages of sepsis, the host's inflammatory response is believed to be in a hyperactive state with a predominant increase in the production of pro-inflammatory cytokines that mediate host tissue injury and lethal shock (Cohen, J., Nature, (2002), 420 (6917):885-91).
- COVID-19 caused by SARS-CoV-2, is also characterised by an immune dysfunction rather than a viral load, which leads to abnormal production of pro-inflammatory cytokines (Ma W-T, et al. The protective and pathogenic roles of IL-17 in viral infections: friend or foe? Open Biol. 2019;9(7) : 190109).
- COVID-19 can trigger a cytokine storm in pulmonary tissues through hyperactivation of the immune system and the uncontrolled release of cytokines (Ye Q, Wang B, Mao J. Cytokine storm in COVID-19 and treatment. J Infect. 2020;80:607-13).
- cytokine storm and related interventions include interleukin-6 (IL-6), interleukin-ip (IL-1P), and tumor necrosis factor-alpha (TNF-o) play a very significant role in lung damage in COVID patients with acute respiratory distress syndrome (ARDS), through the impairments of the respiratory epithelium Montazersaheb, S., Hosseiniyan Khatibi, S.M., Hejazi, M.S. et al. COVID-19 infection: an overview on cytokine storm and related interventions. Virol J 19, 92 (2022).
- IL-6 interleukin-6
- IL-1P interleukin-ip
- TNF-o tumor necrosis factor-alpha
- Treatments mainly consist of pharmacotherapy such as steroids, antihistamines and antibiotics.
- Steroids have antiinflammatory and immunosuppressive effects and have good effects, but they are harmful to the intestines, kidneys, liver, bones and brain, and the conditions often recur when treatment is discontinued.
- the invention relates to a method of treating, preventing or ameliorating a disease, disorder or condition associated with inflammation or immune-modulation, comprising administration to a subject in need thereof of an effective amount of a placental extract or an effective amount of a composition comprising a placental extract.
- the invention relates to a composition for use in treating, preventing or ameliorating a disease, disorder or condition associated with inflammation or immune-modulation, wherein the composition comprises a placental extract.
- the invention relates to use of a placental extract, in the manufacture of a medicament or composition for treating, preventing or ameliorating a disease, disorder or condition associated with inflammation or immune-modulation.
- the composition or medicament is a food, drink, food additive, drink additive, food component, drink component, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical.
- the placenta extract is administered at a concentration sufficient to inhibit one or more pro-inflammatory cytokines, including cytokine IL-la, 0, IL-2, IL-3, IL-6, IL-7, IL-9, IL-12, IL-17, IL-18, TNF-a, LT, LIF, Oncostatin, or IFNcla, p, y.
- cytokine IL-la 0, IL-2, IL-3, IL-6, IL-7, IL-9, IL-12, IL-17, IL-18, TNF-a, LT, LIF, Oncostatin, or IFNcla, p, y.
- the placenta extract is administered at a concentration sufficient to stimulate expression of one of more anti-inflammatory cytokine, including IL-4, IL- 10, IL-11, W-13 or TGF .
- the placental extract is derived from a deer, sheep, goat, horse, donkey, rabbit or bovine placenta.
- the placental extract is derived from deer placenta.
- the placental extract is CerviCenta®.
- Preferred methods of extraction from placenta material include solvent extraction, supercritical solvent extraction including supercritical CO2 extraction, distillation, counter current extraction, decoction, percolation, maturation, molecular distillation, microwave extraction, ultrasound extraction, and chromatographic separation.
- the method of extraction may include the steps of contacting the placenta material with a solvent, separating the placenta material from the solvent, and at least partially removing the solvent to yield the extract.
- placenta material is freeze dried and powdered prior to contact with the solvent.
- the solvent is water.
- any suitable organic solvent may be used.
- the solvent may be ethanol or a mixture of any such solvents.
- the extract is prepared by solvent extraction, such as ethanol extraction, followed by distillation or supercritical extraction.
- the placental extract is or comprises dried or powdered placenta material.
- the method of extraction comprises pulverising placenta material by wet grinding, and then powdering or granulating by freeze-, vacuum- or spray-drying, or fluid bed drying or the like.
- the placenta material is first dried, for example by freeze- or vacuumdrying, and then optionally ground into powder.
- the composition or medicament is provided in a delivery formulation selected from the group consisting of tablets, capsules, liquids, oils, suspensions, emulsions, pastes, jellies, puddings, solutions, and powders.
- the composition or medicament comprises, consists essentially of or consists of the placenta extract.
- the placenta extract comprises, consists essentially of, or consists of placenta material prepared by solvent extraction, dried or powdered placenta material, and/or combinations thereof.
- the composition comprises or the medicament comprises at least about 0.1, 0.2, 0.5, 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, 99.5, 99.8 or 99.9% by weight of the placental extract and useful ranges may be selected between any of these foregoing values (for example, from about 0.1 to about 50%, from about 0.2 to about 50%, from about 0.5 to about 50%, from about 1 to about 50%, from about 5 to about 50%, from about 10 to about 50%, from about 15 to about 50%, from about 20 to about 50% j from about 25 to about 50%, from about 30 to about 50%, from about 35 to about 50%, from about 40 to about 50%, from about 45 to about 50%, from about 0.1 to about 60%, from about 0.2 to about 60%, from about 0.5 to about 60%, from about 1 to about 60%, from about 5 to about 60%, from about 10 to about 60%, from about 15 to about 60%, from about 20 to about 60% j from about 25 to about 60%
- the composition comprises or the medicament comprises, at least about 0.001, 0.01, 0.05, 0.1, 0.15, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19 grams or more of the placenta extract and useful ranges may be selected between any of these foregoing values (for example, from about 0.01 to about 1 grams, about 0.01 to about 10 grams, about 0.01 to about 19 grams, from about 0.1 to about 1 grams, about 0.1 to about 10 grams, about 0.1 to about 19 grams, from about 1 to about 5 grams, about 1 to about 10 grams, about 1 to about 19 grams, about 5 to about 10 grams, and about 5 to about 19 grams).
- the composition comprises or the medicament comprises, at least about 1, 10, 50, 100, 125, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900 or lOOOmg or more of the placenta extract and useful ranges may be selected between any of these foregoing values (for example, from about 10 to about lOOOmg, from about 50 to 1000 mg, from about 75 to about 800mg, from about 75 to about 500mg, from about 75 to about 350mg, from about 75 to about 300mg, from about 75 to about 250mg, from about 100 to about 350mg, from about 100 to about 300mg, from about 100 to about 250mg, from about 100 to about 200mg, from about 100 to about 150mg, more preferably from about 100 to about 125mg).
- lOOOmg from about 50 to 1000 mg, from about 75 to about 800mg, from about 75 to about 500mg, from about 75 to about 350mg, from about 75 to about 300mg, from
- the composition comprises, the medicament comprises, or the method comprises administration of placenta extract in an amount of about 125mg, suitable for administration twice daily, or 250mg, suitable for administration once per day.
- the composition comprises, the medicament comprises, or the method comprises administration of placenta extract in an amount of about lOOmg or 125mg, suitable for administration twice daily, or 200mg or 250mg, suitable for administration once per day.
- the composition comprises, the medicament comprises, or the method comprises administration of about 40% to 90% by weight of placenta extract, for example about 50% to 80% by weight, or about 60% to 75% by weight placenta extract.
- composition or medicament further comprises about 0.1, 0.5, 1, 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50% by weight another anti-inflammatory agent and useful ranges may be selected between any of these foregoing values (for example, from about 0.1 to about 50%, from about 0.2 to about 50%, from about 0.5 to about 50%, from about 1 to about 50%, from about 5 to about 50%, from about 10 to about 50%, from about 15 to about 50%, from about 20 to about 50% j from about 25 to about 50%, from about 30 to about 50%, from about 35 to about 50%, from about 40 to about 50%, and from about 45 to about 50%).
- another anti-inflammatory agent for example, from about 0.1 to about 50%, from about 0.2 to about 50%, from about 0.5 to about 50%, from about 1 to about 50%, from about 5 to about 50%, from about 10 to about 50%, from about 15 to about 50%, from about 20 to about 50% j from about 25 to about 50%, from about 30 to about 50%, from about 35 to about 50%, from about 40 to about 50%, and from about 45 to about 50%).
- composition or medicament further comprises a carrier, for example a pharmaceutically acceptable carrier.
- composition or medicament is in the form of a tablet, a caplet, a pill, a hard or soft capsule or a lozenge.
- composition or medicament is in the form of a cachet, a dispensable powder, granules, a suspension, an elixir, a liquid, or any other form that can be added to food or drink, including for example water or fruit juice.
- composition or medicament further comprises one or more constituents (such as antioxidants) which prevent or reduce degradation of the composition during storage or after administration.
- composition or medicament is or is formulated as a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical.
- the composition or medicament is formulated as a powder, liquid, food bar, spread, sauce, paste, jelly, pudding, soup base, ointment, tablet or capsule.
- composition or medicament is formulated for oral, nasal, or parenteral (including topical, subcutaneous, intramuscular, and intravenous) administration.
- composition or medicament is formulated for ingestion, inhalation, or topical application.
- composition or medicament is formulated for inhalation, preferably it is formulated as an inhalable powder, solution, or aerosol.
- composition or medicament is formulated for topical application, preferably it is formulated as an ointment, cream, or lotion.
- the dose of the composition or medicament administered, the period of administration, and the general administration regime may differ between subjects depending on such variables as the severity of symptoms of a subject, the type of disorder to be treated, the mode of administration chosen, and the age, sex and/or general health of a subject.
- the inventors contemplate administration of from about 1 mg to about 1000 mg per kg body weight of a composition or medicament of the invention is administered per day, preferably about 50 to about 500 mg per kg per day.
- the inventors contemplate administration of from about 0.05 mg to about 250 mg per kg body weight of a pharmaceutical composition or medicament according to the invention. It should be appreciated that administration may include a single daily dose or administration of a number of discrete divided doses as may be appropriate.
- the invention may also be said broadly to consist in the parts, elements and features referred to or indicated in the specification of the application, individually or collectively, in any or all combinations of two or more of said parts, elements or features, and where specific integers are mentioned herein which have known equivalents in the art to which the invention relates, such known equivalents are deemed to be incorporated herein as if individually set forth.
- Figure 1 provides a determination of protein integrity of placenta extracts: protein extracts were resolved on a 4-20% BioRad gradient gel and subsequently stained with Coomassie Brilliant Blue as indicated. The following order can be observed. Lanes 1 to 10 from left to right: BioRad Precision Plus Protein Standard: Mw (kDa) from top to the bottom: 250 I 150 /100 / 75 / 50 / 37 / 25 / 20 / 15. Lane 2: culture medium, lane 3: 0.9% NaCI, lane 4: PBS/1% Triton X100, lane 5: PBS/1% SDS, lane 6: overspill from lane 7, lane 7: distilled water, lanes 8/9: PBS.
- Figure 2 provides an assessment of IL-lbeta.
- PBMCs were treated with DPE and stimulating agents as described.
- Supernatants were isolated and transferred to the MSD U-Plex multiplexing platform in various dilutions (1/5, 1/20 and 1/50) to define an optimal range of reactivity. Best reactivities were achieved in a 1/5 dilution of the test extract. These data are depicted here.
- Zymosan 2 (1 pg/mL), Endotoxin 1 (0.05 EU/mL).
- HSKA (10 8 cells).
- X-axis reactivity (EC units), Y-Axis: stimulus
- Figure 3 provides an assessment of IL-6.
- PBMCs were treated with DPE and stimulating agents as described
- Supernatants were isolated and transferred to the MSD U-Plex multiplexing platform in various dilutions (1/5, 1/20 and 1/50) to define an optimal range of reactivity. Best reactivities were achieved in a 1/5 dilution of the test extract. These data are depicted here.
- Zymosan 3 0.2 pg/mL
- Endotoxin 1 0.05 EU/mL
- HSKA (10 8 cells).
- DPE 1/5 (12.33 mg/mL)
- DPE 1/20 (3.08 mg/mL and DPE 1/50 (1.23 mg/mL).
- X-axis reactivity (EC units)
- Y-Axis stimulus.
- Figure 4 provides DPE Interference in the induction of IL-lbeta.
- Human PBMCs were pre-treated with DPE as described. Subsequently established stimuli were added at the following concentrations: Zymosan (Ipg/mL), HKSA (1 xlO 8 ), Endotoxin (0.05 EU/mL). Supernatants were collected and analyse on the Mesoscale U-PLEX platform. Data presented here resemble a 1/10 dilution on the Mesoscale platform.
- Figure 5 provides dose finding of DPE in BEAS-2B cells after 24 hours supplementation.
- the present invention is based on the discovery that a placenta extract has useful properties, including anti-inflammatory activity.
- an “effective amount” is the amount required to confer therapeutic effect.
- the interrelationship of dosages for animals and humans is described by Freireich, et al. (1966).
- Body surface area can be approximately determined from height and weight of the subject. See, e.g., Scientific Tables, Geigy Pharmaceuticals, Ardley, New York, 1970, 537.
- Effective doses also vary, as recognized by those skilled in the art, dependent on route of administration, carrier usage, and the like.
- extract refers to a preparation derived from source material, that is in a different form than the original material from which it is derived.
- An extract can be as simple as mechanically ground cellular material, in which case the preparation can be dehydrated to remove water, or it can be a preparation derived by contacting the source material with one or more solvents.
- extract also encompasses preparations that undergo one or more separation and/or purification steps to enrich the content of active agent(s), as well as preparations comprising partially or substantially purified fractions derived from the placenta material.
- pharmaceutically acceptable carrier is intended to refer to a carrier including but not limited to an excipient, diluent or auxiliary that can be administered to a subject as a component of a composition of the invention that does not reduce the activity of the composition and is not toxic when administered in doses sufficient to deliver an effective amount of one or more active agents.
- the formulations can be administered orally, nasally, or parenterally (including topically, intramuscularly, intraperitoneally, subcutaneously, and intravenously).
- cosmetic composition refers to a composition including the compound, having any type of formulation.
- formulations of cosmetics prepared using the composition include creams such as skin creams, nutrition creams, eye creams, massage creams, and cleansing creams; packs; lotions such as nutrition lotion; essences; serums, poultices, ointments; tonics such as skin softeners and nutrition tonics; powders; foundations, and makeup bases.
- the cosmetic composition may be prepared in any formulation selected from the above-listed formulations to be commercialized, and the present disclosure is not limited to the above examples.
- the cosmetic composition according to the present disclosure may be formulated using a general cosmetic preparation method.
- health functional food refers to foods prepared and processed in the form of tablets, capsules, paste, jelly, pudding, soft gel, powder, granules, a liquid, pills, or the like by using raw materials or ingredients having useful functionality in the human body.
- functionality refers to controlling nutrients for the structure of functions of the human body or providing useful effects of hygienic purposes, such as psychological effects, and the like.
- the health function food of the present disclosure may be prepared using a method commonly used in the art, and may be prepared by adding raw materials and ingredients commonly added in the art.
- the formulation of the health function food is not particularly limited so long as it is recognised as a health functional food.
- the health functional food composition of the present disclosure uses a food as a raw material unlike generic drugs, and thus has no side effects that may occur during long-term administration thereof, is highly portable, and may be administered as an adjuvant for enhancing skin moisturizing, exfoliating skin, improving skin elasticity, enhancing skin healing, inhibiting erythema, improving skin wrinkles, and/or alleviating skin photoaging.
- steroids sparing is intended to mean that the dose of steroidal medication administered to a subject is able to be reduced to a level below that administered before the subject began taking a composition of the present invention or began using a method of the present invention.
- the daily or weekly or monthly dose of steroids is able to be reduced by at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 99%.
- a "subject" in accordance with the invention is an animal, preferably a mammal, more preferably a mammalian companion animal or human.
- Preferred companion animals include cats, dogs and horses.
- compositions useful herein are superior, as measured by, for example, the extent of the effect in vitro or in vivo or both, compared to use of individual agents alone.
- the effect of the combination of placenta extract and another agent, such as another anti-inflammatory extract is synergistic if the effect is superior to the effect achievable with the placenta extract alone or the other agent or extract alone.
- the effect of the combination is synergistic if a beneficial effect is obtained in a group of subjects that does not respond (or responds poorly) to a placenta extract or the other agent or extract alone.
- the effect of the combination is synergistic if one of the components is used at its conventional dose and the other component is used at a reduced dose and the effect, as measured by, for example, the extent of the effect in vitro or in vivo or both, is equivalent to or better than that achievable with conventional amounts of either one of the components of the combination treatment alone.
- Related terms such as "synergistic" are to be interpreted similarly.
- treat and its derivatives should be interpreted in their broadest possible context. The term should not be taken to imply that a subject is treated until total recovery. Accordingly, “treat” broadly includes amelioration and/or prevention of the onset of the symptoms or severity of a particular condition.
- placenta extract and compositions comprising placenta extract as described herein are useful in methods for treating or preventing a variety of conditions, including a disease, disorder or condition associated with inflammation or immune-modulation.
- the extract and compositions herein provide an immunomodulatory effect, useful for example in the treatment or prevention of conditions associated with inflammation.
- the placenta extract is administered is in an amount sufficient to treat the inflammatory-related disease by inhibiting pro-inflammatory cytokine expression and/or by stimulating anti-inflammatory cytokines.
- the present uses include, but are not limited to, treating the inflammatory-related disease by preventing inflammation associated with the disease by regulating cytokines involved in the pathological progress, thus preventing the onset the inflammatory-related disease.
- the inflammatory-related disease is selected from the group consisting of diabetes type I; Sjogren's syndrome; uveitis; celiac disease; allergic conjunctivitis; and non-specific colitis.
- inflammatory-related diseases include: arthritis, rheumatoid arthritis, an inflammatory bowel disease; psoriasis; multiple sclerosis; a neurodegenerative disorder; congestive heart failure; stroke; aortic valve stenosis; kidney failure; lupus; pancreatitis; allergy; fibrosis; anemia; atherosclerosis; a metabolic disease; a bone disease; a cardiovascular disease, a chemotherapy/radiation related complication; diabetes type II; a liver disease; a gastrointestinal disorder; an ophthalmological disease; diabetic retinopathy; a pulmonary disorder, a renal disease; dermatitis; HIV-related cachexia; cerebral malaria; ankylosing spondylitis; leprosy; anemia; and fibromyalgia.
- Neurodegenerative disorders disclosed herein include: Alzheimer's disease and Parkinson disease, geroscience, osteoporosis, macular degeneration, healthspan extension; the inflammatory bowel disease is selected from the group consisting of: Crohn's disease or ulcerative colitis; the gastrointestinal complication is diarrhea; the liver disease is selected from the group consisting of: an autoimmune hepatitis, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis, or fulminant liver failure; the bone disease is osteoporosis; the pulmonary disorder is selected from the group consisting of: allergic rhinitis, asthma, chronic obstructive pulmonary disease, chronic granulomatous inflammation, cystic fibrosis, and sarcoidosis; the cardiovascular disease is selected from the group consisting of: atherosclerotic cardiac disease, congestive heart failure and restenosis, thrombosis (Atrial fibrillation, AF), Hemodynamic Stress, Metabolic Syndrome
- AUTOIMMUNE - autoimmune and inflammatory disease hypertension, fatigue, autism spectrum disorders, bipolar disorder, cancers, kidney transplant, Kawasaki disease;
- BRAIN HEALTH cognitive impairment, vascular and neurodegenerative disorders, Alzheimer's disease, brain morphology, tumour necrosis;
- LUNG / RESPIRATORY HEALTH - macrophages chronic respiratory disease, pulmonary fibrosis, autophagy, exuberant, dysregulated inflammation, interferon (Type I IFNs) response, cystic fibrosis (CF) lung disease, acute respiratory distress Syndrome, Chronic Bronchitis, chronic obstructive pulmonary disease (COPD), respiratory syncytial virus infection (RSV), mucus obstruction and neutrophilic inflammation;
- CARDIOVACULAR HEALTH - coronary artery disease HV+ individuals
- cardiovascular disease CVD
- Atherosclerosis Thrombosis
- Thrombosis Thrombosis
- MetS Hemodynamic Stress
- HRV heart rate variability
- ETR erythematotelangiectatic Rosacea
- DEPRESSION - central nervous system disorders chronic stress, depression, dementia, major depressive disorder (MDD);
- ORGANS Asthma-chronic obstructive pulmonary disease (ACOS), kidney disease, inflammatory bowel disease, organ disease (heart, pancreas, liver, kidney, lung, brain, intestinal tract, reproductive system, tissue damage); CANCERS - liver cancers, breast cancer, gastric cancer, intestinal cancer, lung cancer, artery disease;
- the compound is in an amount to inhibit pro-inflammatory cytokine expression and/or to stimulate anti-inflammatory cytokine expression.
- the compound is preferably in an amount to inhibit at least 30% expression of one or more of the pro-inflammatory cytokines selected from the group consisting of: IL-la, 3, IL-2, IL-3, IL-6, IL-7, IL-9, IL-12, IL-17, IL-18, TNF-a, LT, LIF, Oncostatin, and IFNcla, 3, y: More preferably at least 40% expression of the cytokine is inhibited and most preferably 50% or more is inhibited.
- the compound is preferably in an amount to stimulate anti-inflammatory cytokine expression.
- the compound is preferably in an amount to increase the antiinflammatory cytokine selected from the group consisting of: cytokine IL-4, IL-10, IL-11, W-13 or TGF3 by at least 25%, more preferably at least 50%, and most preferably at least 75%.
- the condition is joint inflammation, muscle inflammation, tendon inflammation, ligament inflammation, joint damage, joint sprain or strain, muscle sprain, muscle strain, cartilage damage, osteoarthritis, rheumatoid arthritis, an atopic condition, an allergy, arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression.
- the condition is joint inflammation.
- the condition is muscle inflammation, tendon inflammation, ligament inflammation, joint damage, joint sprain or strain, muscle sprain or strain, or cartilage damage.
- the conditions is osteoarthritis or rheumatoid arthritis.
- the condition is an atopic condition.
- condition is an allergy.
- condition is arteriosclerosis, atherosclerosis, heart disease, high blood pressure, blood clots, hypotension, vasoconstriction, cancer, or depression.
- treatment is with steroid sparing effect.
- the combinations described herein are useful for reducing inflammation caused by skin/tissue injury, and are useful in atopic dermatitis, psoriasis, actinic keratosis, rosacea, skin tissue healing and other chronic skin disorders.
- the combinations described herein are useful for a disease, disorder or condition of the lung.
- said disease, disorder or condition is (a) associated with or caused by an immune response; (b) an interstitial lung disease; (c) an obstructive lung disease; (d) an acute lung injury; or (e) a lung injury caused by a neoplastic or paraneoplastic disease, pneumonia, or cystic fibrosis.
- said disease, disorder or condition associated with or caused by an immune response is an autoimmune disease, or a graft-versus-host disease.
- said autoimmune disease is rheumatoid arthritis, scleroderma, inflammatory bowel disease, or systemic lupus erythematosus.
- said interstitial lung disease is interstitial pulmonary fibrosis.
- said obstructive lung disease is asthma, bronchitis, acute respiratory distress syndrome or chronic obstructive pulmonary disease.
- said lung disease, disorder, or condition is an acute lung injury.
- said acute lung injury is one or more of physical trauma, a chemical injury, e.g., a chemical burn, smoke inhalation, or exposure to a toxic substance.
- said lung disease, disorder, or condition is an injury caused by a neoplastic or paraneoplastic disease.
- the disease, disorder or condition is one or more of a fibrotic disease of the lung, acute respiratory distress syndrome (ARDS), COVID-19, chronic obstructive pulmonary disease (COPD), emphysema, asthma, a viral or bacterial infection of the lung, pneumonia (including chemically-induced pneumonia), or cystic fibrosis.
- the fibrotic disease of the lung is interstitial lung disease (diffuse parenchymal lung disease).
- the interstitial lung disease is silicosis, asbestosis, berylliosis, systemic sclerosis, polymyositis, or dermatomyositis.
- the interstitial lung disease is caused by an antibiotic, a chemotherapeutic drug, an antiarrhythmic drug, or an infection.
- the disease, disorder or condition of the lung is associated with or caused by a harmful, deleterious, inappropriate or unwanted immune response, e.g., inflammation, wherein said disease, disorder or condition affects, or manifests symptoms in, the lungs.
- said disease, disorder or condition is one or more of lupus, e.g., lupus erythematosus, scleroderma, or a rheumatological disease (e.g., rheumatoid arthritis).
- said disease, disorder or condition is rheumatoid lung disease (RLD), e.g., rheumatoid lung disease associated with rheumatoid arthritis.
- RLD rheumatoid lung disease
- the administration is sufficient to cause a detectable improvement in one or more symptoms of RLD, or sufficient to detectably reduce or slow the progression of one or more symptoms of RLD, e.g., in a lung of the individual.
- said symptom of RLD is a condition adjunct to RLD.
- said condition adjunct to RLD is an infection, e.g., a viral infection of the lungs, or fibrosis of the lungs (e.g., as a consequence of methotrexate therapy).
- the disease, disorder or condition is lupus erythematosus, e.g., systemic lupus erythematosus (SLE).
- said symptom of lupus erythematosus is one or more of lung and/or pleural inflammation, pleurisy, pleuritis, pleural effusion, lupus pneumonitis, or chronic diffuse interstitial lung disease.
- the combinations described herein are useful for the prevention or treatment of viral diseases and/or for inhibiting virus activation, in which said virus is selected from the group consisting of herpes virus, such as cytomegalovirus (CMV); influenza virus, such as H1N1, H3N2, H5N1 or H5N7 virus; para mixovirus, such as measles; respiratory syncytial virus; coronaviruses, such as SARS or SARS-CoV-2 (Covid-19); HIV Virus; hepatitis virus; or rotavirus.
- CMV herpes virus
- influenza virus such as H1N1, H3N2, H5N1 or H5N7 virus
- para mixovirus such as measles
- respiratory syncytial virus coronaviruses, such as SARS or SARS-CoV-2 (Covid-19)
- HIV Virus hepatitis virus
- rotavirus rotavirus
- compositions, medicaments and methods of treatment or prevention described and useful herein may employ compositions as described below.
- Placenta extract and compositions comprising placenta extract as described herein are useful in methods to treat, including prevent, reduce, ameliorate, and/or eliminate, signs and results of dermatological aging of skin, especially wrinkles and fine lines, blotches, red skin, dark spots and/or to improve the aesthetic appearance of skin, stimulate collagen production, increase elasticity and/or skin tone and hydration.
- the combinations provide treatment for wrinkles, fine lines and other signs of dermatological aging (i.e., intrinsic aging) or sunlight exposure of the skin (i.e., extrinsic aging).
- treating and treatment include and encompass preventing, reducing, ameliorating, improving, alleviating, and/or eliminating the dermatological effects of aging and sun exposure, with particular regard to wrinkles, fine lines, folds, furrows, creases of the skin, and the like.
- the present invention further encompasses the treatment, as defined above, of "marionette” lines that run on either side of the mouth, as well as lines on the forehead, and the perpendicular lines between the brows.
- compositions and methods are also suitable for use in treating, as defined above, dermatological conditions of the skin in numerous areas of the body, including, without limitation, the face, forehead, neck, arms, hands, legs, knees, feet, chest, back, groin, buttocks, and the like.
- compositions, formulations and methods containing materials newly determined to be useful in the treatment of dermatological aging of skin especially wrinkles, fine lines, folds, furrows and other signs of aging skin, blotches, red skin, dark spots and/or to improve the aesthetic appearance of skin, stimulate collagen production, increase elasticity and/or skin tone and hydration.
- the contraction or hypercontraction of certain muscles is related to the appearance of wrinkles, fine lines, etc.
- the relaxation of such muscles, and/or the control or modulation of the contraction of such muscles, by the newly-determined action of the placental extracts of the present invention can serve a pivotal function in the treatment, prevention, reduction, amelioration, or elimination of wrinkles, fine lines, folds, furrows and the like.
- compositions which include, without limitation, topically applied sunscreens, anti-oxidants, antiinflammatories, cosmetics, including makeups, anti-aging formulations, e.g, creams for fine lines and/or wrinkles, topicals, skin permeants antiperspirants, deodorants and the like.
- ingredients, components, or compounds that are formulated in such compositions in a variety of product forms, e.g., transdermals, such as patches, and the like are encompassed, particularly for topical administration.
- compositions comprising the disclosed combinations preferably for topical administration without inducing significant irritation.
- compositions are preferably delivered by, but not limited to, the use of targeted delivery systems, for example, liposomes, microspheres, transdermal patches, and the like, so that the actives can more readily reach and affect the muscle layer of the area of application, e.g., face or neck, or the dermal layer of the skin.
- Compositions comprising the disclosed combinations, including liposome formulations can be administered by direct injection subcutaneously, intradermally, or through iontophoresis, to deposit the active agents at the sites requiring muscle relaxation or decontraction.
- the present invention provides the disclosed combinations and methods thereof which can improve the aesthetic appearance of the skin by treating, including preventing, ameliorating and/or reducing at least one of the following: dermatological aging, especially chronological, actinic or hormonal aging.
- dermatological aging especially chronological, actinic or hormonal aging.
- the improvement preferably results following topical application of a product or formulation containing one or more of the disclosed combinations as described herein.
- a composition described herein may be formulated as a food, drink, food additive, drink additive, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical.
- a composition of the invention is formulated as a powder, liquid, food bar, spread, sauce, ointment, tablet or capsule. Appropriate formulations may be prepared by an art skilled worker with regard to that skill and the teaching of this specification.
- compositions described herein may be formulated to allow for administration to a subject by any chosen route, including but not limited to oral, nasal or parenteral (including topical, subcutaneous, intramuscular and intravenous) administration.
- a pharmaceutical composition useful in the invention may be formulated with an appropriate pharmaceutically acceptable carrier (including excipients and diluents) selected with regard to the intended route of administration and standard pharmaceutical practice.
- a composition of the invention can be administered orally as a powder, liquid, tablet or capsule, or topically as an ointment, cream or lotion.
- Suitable formulations may contain additional agents as required, including emulsifying, antioxidant, flavouring or colouring agents, and may be adapted for immediate-, delayed-, modified-, sustained-, pulsed- or controlled- release.
- compositions useful herein may be used alone or in combination with one or more other therapeutic agents.
- the therapeutic agent may be a food, drink, food additive, drink additive, food component, drink component, dietary supplement, nutritional product, medical food, nutraceutical, medicament or pharmaceutical.
- the administration of a composition of the invention and other therapeutic agent may be simultaneous or sequential.
- Simultaneous administration includes the administration of a single dosage form that comprises all components and the administration of a composition of the invention and other therapeutic agent in separate dosage forms at substantially the same time.
- Sequential administration includes the administration of a composition of the invention and other therapeutic agent according to different schedules, preferably so that there is an overlap in the periods during which the composition of the invention and other therapeutic agent are provided.
- Suitable agents with which the compositions may find use in the invention can be coadministered include antihistamines, anti-inflammatories, anti-rheumatics, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 selective inhibitors, muscle relaxants, including combinations of any two or more thereof, and other suitable agents known in the art.
- NSAIDs non-steroidal anti-inflammatory drugs
- the dose of the composition administered, the period of administration, and the general administration regime may differ between subjects depending on such variables as the severity of symptoms of a subject, the type of disorder to be treated, the mode of administration chosen, and the age, sex and/or general health of a subject.
- the inventors contemplate administration of from about 1 mg to about 1000 mg per kg body weight or more of a composition of the invention is administered per day, preferably about 50 to about 500 mg per kg per day.
- the inventors contemplate administration of from about 0.05 mg to about 250 mg per kg body weight of a pharmaceutical composition according to the invention. It should be appreciated that administration may include a single daily dose or administration of a number of discrete divided doses as may be appropriate.
- compositions described herein also include a cosmetic composition having an effect of enhancing skin moisturising, exfoliating skin, enhancing skin elasticity, enhancing skin healing, inhibiting erythema, improving skin wrinkles, and/or alleviating skin photoaging.
- the cosmetic composition is prepared in any one formulation selected from the group consisting of a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, a nutrition cream, a moisturizing cream, a hand cream, an essence, a pack, a mask pack, a mask sheet, an exfoliating agent, a soap, a shampoo, a cleansing foam, a cleansing lotion, a cleansing cream, a body lotion, a body cleanser, an emulsion, a press powder, a loose powder, and an eye shadow.
- a skin lotion a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, a nutrition cream, a moisturizing cream, a hand cream, an essence, a pack, a mask pack, a mask sheet, an exfoliating agent, a
- an amount of the placenta extract ranges from about 0.05 to about 1% weight with respect to a total weight of the cosmetic composition.
- an amount of the placenta extract ranges from about 0.05 to about 0.5% weight, from about 0.05 to about 0.4% weight, from about 0.05 to about 0.35% weight, from about 0.1 to about 0.5% weight, from about 0.1 to about 0.4% weight, from about 0.135 to about 0.35% weight, or from about 0.15 to about 0.2% weight.
- the composition is for application to skin, for example a face mask and comprises 0.13% weight placenta extract.
- the composition is a cream, gel or lotion for anti-aging uses, and comprises 0.135% to 0.35% weight placenta extract.
- the composition is a cream, gel or lotion for whitening, and comprises 0.15 to 0.2% weight placenta extract.
- the cosmetic composition of the present disclosure may further include, in addition to the placenta extract, other additives such as an excipient, a carrier, and the like, and general ingredients added to general skin cosmetics may be applied to the cosmetic composition and mixed therewith in a needed amount.
- other additives such as an excipient, a carrier, and the like
- general ingredients added to general skin cosmetics may be applied to the cosmetic composition and mixed therewith in a needed amount.
- the cosmetic composition of the present disclosure may further include a transdermal penetration enhancer.
- transdermal penetration enhancer refers to a composition that allows a desired component to permeate vascular cells of the skin at a high absorption rate.
- Non-limiting examples of the transdermal penetration enhancer may include other phospholipid components, liposomal components, and the like used in lecithin cosmetics.
- oil that may be mainly used as an oil component may be at least one selected from vegetable oil, mineral oil, silicone oil, and synthetic oil. More particularly, mineral oil, cyclomethicone, squalane, octyldodecyl myristate, olive oil, Vitis vinifera seed oil, macadamia nut oil, glyceryl octanoate, castor oil, ethylhexyl isononanoate, dimethicone, cyclopentasiloxane, sunflower seed oil, and the like may be used.
- the surfactant may be a general surfactant such as a nonionic surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant, a phospholipid, or the like, and may be, for example, sorbitan sesquinoleate, polysorbate 60, glyceryl stearate, lipophilic glyceryl stearate, sorbitan oleate, sorbitan stearate, diacetyl phosphate, sorbitan stearate/sucrose cocoate, glyceryl stearate/polyethylene glycol-100 stearate, ceteareth-6 olivate, arachidyl alcohol/behenyl alcohol/arachidyl gluco side, polypropylene glycol-
- a surfactant may be a general surfactant such as a nonionic surfactant, an anionic surfactant, a cationic surfactant, an amphoteric
- the higher alcohol may be a C12 to C20 alcohol, for example, cetyl alcohol, stearyl alcohol, octyldodecanol, isostearyl alcohol, or the like, and these higher alcohols may be used alone or at least two thereof may be used in combination.
- a thickening agent selected from carbomer, xanthan gum, bentonite, magnesium aluminium silicate, cellulose gum, dextrin palmitate, and the like may further be added.
- the cosmetic composition according to the present disclosure may further include, according to need, components, for example, a medicinal ingredient such as higher fatty acids, vitamins, or the like; a UV screening agent; an antioxidant (butylhydroxyanisole, gallic acid propyl, erythorbic acid, tocopheryl acetate, butylated hydroxytoluene, or the like); a preservative (methylparaben, butylparaben, propylparaben, phenoxyethanol, imidazolidinyl urea, chlorphenethine, or the like); a colorant, a pH adjusting agent (triethanolamine, citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumarate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, or the like); a moisturizing agent (glycerin, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycer
- the cosmetic composition of the present disclosure may further include an adjuvant for supplying an essential nutrient to the skin, for example, an adjuvant with natural flavor or cosmetic flavor, or medicinal herbs, but may include any adjuvant without being limited to these examples.
- an adjuvant for supplying an essential nutrient to the skin for example, an adjuvant with natural flavor or cosmetic flavor, or medicinal herbs, but may include any adjuvant without being limited to these examples.
- Compositions described herein also include a health functional food composition having an effect of enhancing skin moisturizing, exfoliating skin, enhancing skin elasticity, inhibiting erythema, improving skin wrinkles, and/or alleviating skin photoaging.
- the health functional food composition is prepared in any one formulation selected from the group consisting of tablets, granules, powder, soft gel, paste, jelly, pudding, capsules, a liquid solution (such as a beverage), and pills.
- an amount of the placenta extract ranges from about 50 to about 500mg when present in a health functional food composition in the form of a beverage.
- an amount of the placenta extract ranges from about 50 to about 350mg, from about 55 to about 350mg, from about 60 to about 300mg, from about 65 to about 250mg, from about 65 to about 200mg, from about 65 to about 180mg, from about 65 to about 160mg, or from about 65 to about 155mg.
- the health functional food composition in the form of a shot and comprises from about 10 to about lOOmg placenta extract, from about 10 to about 80mg, from about 20 to about 70mg, or from about 25 to about 50mg.
- the cosmetic composition or the health functional food composition may further include a skin wrinkle improving ingredient.
- the skin wrinkle improving ingredient includes one or more selected from the group consisting of vitamin C, retinoic acid, a transforming growth factor (TGF), an animal placenta-derived protein, betulinic acid, and a chlorella extract.
- TGF transforming growth factor
- Freeze-dried Deer Placenta powder was dissolved in various solvents to create a final test extract solubilising major parts of the basic material and being compliant with physiological testing.
- the protein concentration of the extract (DPE) was determined by absorption at 280nm. Protein integrity was checked by SDS-PAGE I Coomassie Brilliant Blue staining.
- Cytotoxicity was determined according to the demands of the ISO 10993-5, 2009. Test performance will be described below.
- PBMCs peripheral blood mononuclear cells
- Table 1 Reagents and Media Table 2: Generation of placenta extracts / Determination of protein concentration and integrity
- Freeze dried deer placenta powder was dissolved in various solvents to assure creating a final test extract solubilising major parts of the basic material and being compliant with physiological testing.
- the protein concentration of the extract was determined by absorption at 280nm. Protein integrity was checked by SDS-PAGE I Coomassie Brilliant Blue staining ( Figure 1).
- Cytotoxicity was determined according to the demands of the ISO 10993-5, 2009. In this special context various dilutions ranging from a Vi dilution to a 1 /1000 dilution of the test extract were subjected for evaluation of a cytotoxic potential on the test cell line L929. The read out was generated by conversion of the vital dye XTT (ISO 10993-5. Annex D) in combination with a visual inspection of the cultures.
- NC Negative Control
- PC Positive Control
- PBMCs were directly treated with the indicated extracts and stimuli (16h, 37°C, 5%CO2) or after 3h preincubation with (1.23 mg/mL) for the same time period. For determination of immune modulatory effects 3 different concentrations of were chosen. Beginning from a starting extract (61. 6 mg / mL) the following dilutions were tested
- Immune modulatory stimuli Endotoxin (0.1 1 0.05 I 0.01 EU/mL f.c.); Zymosan (5 I 1 / 0.2 mg/mL f.c.); Heat inactivated Staph. Aureus (1 x 10 8 / lx 10 7 cells f.c.)
- Interleukin 1 beta (IL- 13) is regarded as a pro-inflammatory cytokine and is an important mediator of the inflammatory response,
- Interleukin 6 is an interleukin that acts as a pro-inflammatory cytokine, and there is some evidence that IL-6 can be used as an inflammatory marker for severe COVID-19 infection with poor prognosis.
- IL-6 Interleukin 6
- DPE treatment of human PBMCs at a concentration of 1.23 mg/mL prior to the addition of the indicated stimuli it can be observed that the IL-6 expression by Zymosan at a DPE dependent repression (-24.9%).
- Interleukin 10 (IL-10) is regarded as anti-inflammatory cytokine with numerous functions in the regulation of the immune system.
- IL-10 expression by HKSA was induced (19.3%) by DPE.
- PBMCs Human PBMCs were pretreated with DPE as described. Subsequently established stimuli were added at the following concentrations: Zymosan 2 (Ipg/mL), HKSA 1 (1 xlO 8 ), Endotoxin 1 (0.05 EU/mL). Supernatants were collected and analyzed on the Mesoscale U-PLEX platform. Data presented here resemble a 1/10 dilution on the Mesoscale platform.
- DPE treatment itself did not induce the expression of TNF-alpha.
- the reactivity of the stimulator Endotoxin was also in the background and was neither repressed nor induced by DPE pre-treatment of human PBMCs.
- DPE immune modulatory effect of DPE
- pretreatment of human PBMC in a non cytotoxic concentration of DPE (1.23 mg/mL) prior to stimulation with strong activators such as Endotoxin, Zymosan and Heat killed Staph, aureus it could be observed that DPE reduced the Zymosan dependent induction of IL-lbeta, IL-6, and TNF-alpha.
- a general effect on the expression of IL- lbeta could be observed.
- DPE was also shown to induce expression of the antiinflammatory cytokine IL-10 in response to Heat killed Staph. Aureus.
- COVID-19 caused by SARS-CoV-2, is characterised by an immune dysfunction rather than a viral load, which leads to abnormal production pf pro-inflammatory cytokines.
- COVID-19 can trigger a cytokine storm in pulmonary tissues through hyperactivation of the immune system and the uncontrolled release of cytokines.
- Pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-ip (IL-ip), and tumor necrosis factor-alpha (TNF-o) play a very significant role in lung damage in COVID patients with acute respiratory distress syndrome (ARDS), through the impairments of the respiratory epithelium.
- ARDS acute respiratory distress syndrome
- Test product DPE (Deer Placenta Powder, Lot no. NPR00/65 #2/2R008). Stored refrigerated at 4°C.
- Deer Placenta powder (lOOmg/mL) was dissolved in cell culture medium (KGM2, Promocell) without additives and incubated for 24 ⁇ 2 hours at 37 ⁇ 1 °C.
- the extract (DPE) was centrifugated (2 min, 14000 rpm, RT) and filtered (0.4pm). The protein concentration of the extract was determined by absorption measurement at 280nm.
- the working concentrations of the DPE was assessed on the basis of their effect on cell viability.
- a neutral red uptake assay was performed.
- the BEAS-2B immortalized Human Bronchial Epithelial Cell Line was used.
- the BEAS-2B cell line is used as an in-vitro model for a variety of diseases based on inflammatory processes, such as asthma, infections, ARDS or COVID-19.
- BEAS-2B cells were supplemented for 24 hours with three different concentrations of the DPE or left unsupplemented (control). End concentrations of DPE were: 3.6 mg/mL; 1.8 mg/mL; 0.9 mg/mL.
- T-lymphocytes were isolated from freshly withdrawn human blood samples using Pan T Cell Isolation Kit (Miltenyi Biotec) and activated using T Cell TransAct (Miltenyi Biotec).
- activated T-lymphocytes were added to the pre-supplemented cells for 1 h. After further 24 hours supernatant samples were withdrawn for cytokine analysis.
- IL-10 concentration in the supernatant was determined by ELISA techniques (Manufacturer: RnD Systems D1000B; Lot / Exp: P322071 18.10.2022).
- Extract preparation Protein content was determined photometrically by 280 nm method using a NanoQuant Plate and Infitite 200Pro Plate Reader (Tecan).
- Protein content in deer placenta powder extract 25.33 mg/mL
- the cells were pre-supplemented for 24 hours with three different concentrations of the deer placenta extracts (Cl : 3.6 mg/mL; C2: 1.8 mg/mL; C3: 0.9 mg/mL) or left unsupplemented (control).
- the cells were co-cultured with freshly isolated and activated lymphocytes or co-cultured with not activated lymphocytes. After 24 hours supernatant samples were withdrawn for cytokine analysis.
- Activated lymphocytes were chosen as representative for COVID-19 as trigger for the inflammatory processes in the in vitro test system.
- IL-10 was not detectable in supernatants of BEAS-2B cultures with not activated lymphocytes. Upon stress induced by activated lymphocytes, IL-10 was detectable in all groups. IL-10 release was enhanced by 1.0 mg/mL DPE compared to control.
- compositions and methods of the invention may be employed to treat or prevent one or more of the conditions discussed above.
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KR1020237045286A KR20240017012A (en) | 2021-12-24 | 2022-12-13 | placental composition |
AU2022419516A AU2022419516A1 (en) | 2021-12-24 | 2022-12-13 | Placental composition |
TW111149749A TW202333756A (en) | 2021-12-24 | 2022-12-23 | Placental composition |
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2128514C1 (en) * | 1997-11-13 | 1999-04-10 | Общество с ограниченной ответственностью "НИР" | Method of anti-inflammatory agent preparing |
JP2002226384A (en) * | 2001-02-02 | 2002-08-14 | Ichimaru Pharcos Co Ltd | Cosmetic composition |
KR20090116063A (en) * | 2008-05-06 | 2009-11-11 | 재단법인 제주하이테크산업진흥원 | Composition containing sus domesticus placenta extract |
KR20100000026A (en) * | 2008-06-24 | 2010-01-06 | 재단법인 제주하이테크산업진흥원 | Composition for improving a atopy epidermal inflammation using pig placenta |
CN101703259A (en) * | 2009-11-05 | 2010-05-12 | 辽宁大学 | Method for deeply processing deer placenta |
WO2021211961A1 (en) * | 2020-04-17 | 2021-10-21 | Crown Scientific, L.L.C. | Regenerative nonsteroidal anti-inflammatory compositions, methods of production, and methods of use thereof |
-
2022
- 2022-12-13 KR KR1020237045286A patent/KR20240017012A/en active Search and Examination
- 2022-12-13 WO PCT/IB2022/062160 patent/WO2023119063A1/en active Application Filing
- 2022-12-13 AU AU2022419516A patent/AU2022419516A1/en active Pending
- 2022-12-23 TW TW111149749A patent/TW202333756A/en unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2128514C1 (en) * | 1997-11-13 | 1999-04-10 | Общество с ограниченной ответственностью "НИР" | Method of anti-inflammatory agent preparing |
JP2002226384A (en) * | 2001-02-02 | 2002-08-14 | Ichimaru Pharcos Co Ltd | Cosmetic composition |
KR20090116063A (en) * | 2008-05-06 | 2009-11-11 | 재단법인 제주하이테크산업진흥원 | Composition containing sus domesticus placenta extract |
KR20100000026A (en) * | 2008-06-24 | 2010-01-06 | 재단법인 제주하이테크산업진흥원 | Composition for improving a atopy epidermal inflammation using pig placenta |
CN101703259A (en) * | 2009-11-05 | 2010-05-12 | 辽宁大学 | Method for deeply processing deer placenta |
WO2021211961A1 (en) * | 2020-04-17 | 2021-10-21 | Crown Scientific, L.L.C. | Regenerative nonsteroidal anti-inflammatory compositions, methods of production, and methods of use thereof |
Non-Patent Citations (2)
Title |
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HEO JH ET AL.: "Topical anti-inflammatory and anti-oxidative effects of porcine placenta extracts on 2,4-dinitrochlorobenzene-induced contact dermatitis", BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE, vol. 18, no. 1, 2018, XP021263769, DOI: 10.1186/s12906-018- 2396-1 * |
LEE K. H., PARK HYUN JUNG, SEO H. G., KIM J. H., LIM G. S., LEE W. Y., KIM N. H., LEE J. H., JUNG H. S., SUNG S. H., SONG H.: "Immune modulation effect of porcine placenta extracts in weaned the pig", JOURNAL OF ANIMAL SCIENCE, vol. 91, no. 5, 1 May 2013 (2013-05-01), US , pages 2405 - 2413, XP093077797, ISSN: 0021-8812, DOI: 10.2527/jas.2012-5208 * |
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