WO2018012901A1 - Composition pour la protection des cellules contenant de la cyclo-histidine-proline comme ingrédient actif - Google Patents

Composition pour la protection des cellules contenant de la cyclo-histidine-proline comme ingrédient actif Download PDF

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Publication number
WO2018012901A1
WO2018012901A1 PCT/KR2017/007518 KR2017007518W WO2018012901A1 WO 2018012901 A1 WO2018012901 A1 WO 2018012901A1 KR 2017007518 W KR2017007518 W KR 2017007518W WO 2018012901 A1 WO2018012901 A1 WO 2018012901A1
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chp
proline
liver
pharmaceutical composition
kidney
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PCT/KR2017/007518
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English (en)
Korean (ko)
Inventor
유환수
최경미
정회윤
이헌종
전종수
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주식회사 노브메타파마
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Priority claimed from KR1020170088341A external-priority patent/KR102012554B1/ko
Application filed by 주식회사 노브메타파마 filed Critical 주식회사 노브메타파마
Priority to EP20206943.1A priority Critical patent/EP3797788A1/fr
Priority to US16/316,595 priority patent/US10918693B2/en
Priority to CN202110619829.XA priority patent/CN113368248B/zh
Priority to JP2019501912A priority patent/JP6750087B2/ja
Priority to EP17827971.7A priority patent/EP3486252B1/fr
Priority to CN201780042925.4A priority patent/CN109476701B/zh
Publication of WO2018012901A1 publication Critical patent/WO2018012901A1/fr
Priority to US17/172,879 priority patent/US11433114B2/en
Priority to US17/856,729 priority patent/US11890317B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/12—Cyclic peptides with only normal peptide bonds in the ring

Definitions

  • the present invention relates to a cell protective composition
  • a cell protective composition comprising cyclohistidine-proline (Cyclo His-Pro, CHP) as an active ingredient.
  • Cyclo Histidine-Proline is a naturally occurring cyclic dipeptide structurally associated with thyroid stimulating hormone (TRH). Histidine-proline (CHP) is a peptide inherent in animal and human tissues and body fluids. It is found in the blood, semen, gastrointestinal tract, and urine, and is particularly abundant in the prostate. Histidine-proline (CHP) is known to have a variety of physiological activity, such as antidiabetic, anti-obesity, anti-inflammatory, antioxidant action.
  • Apoptosis is an important process for the normal development and function of multicellular organisms. Physiological apoptosis plays an important role in normal processes, but abnormal cell death causes a variety of diseases. For example, inhibition of cell death results in cancer, autoimmune diseases, inflammatory diseases, viral infections, and the like.
  • Apoptosis may also include degenerative neurological diseases such as Alzheimer's, Parkinson's disease, amyotrophic lateral sclerosis, Lou Gehrig's disease, cerebral ischemia, traumatic brain injury, and spinal cord trauma. It is also known to be associated with acute diseases such as spinal cord injury and stroke.
  • degenerative neurological diseases such as Alzheimer's, Parkinson's disease, amyotrophic lateral sclerosis, Lou Gehrig's disease, cerebral ischemia, traumatic brain injury, and spinal cord trauma. It is also known to be associated with acute diseases such as spinal cord injury and stroke.
  • cyclohistidine-proline (Cyclo His-Pro, CHP) inhibits apoptosis of kidney cells and liver cells caused by high drug treatment and protects cells, thus completing the present invention. It was.
  • CHP cyclohistidine-proline
  • Another object of the present invention is to provide a dietary supplement for preventing or improving liver or kidney damage comprising cyclohistidine-proline (CHP) or a food acceptable salt thereof as an active ingredient.
  • CHP cyclohistidine-proline
  • the present invention provides a cytoprotective pharmaceutical composition containing cyclohistidine-proline (CHP) or a pharmaceutically acceptable salt thereof as an active ingredient.
  • CHP cyclohistidine-proline
  • the cells may be kidney cells or liver cells.
  • the composition may inhibit apoptosis.
  • the composition may be to inhibit cell damage caused by the medicament.
  • the medicament is an anticancer agent or antibiotic
  • the anticancer agent is at least one selected from the group consisting of cisplatin, carboplatin, oxaliplatin, and nedaplatin. It may be a platinum-based anticancer agent.
  • the present invention also provides a health functional food for preventing or improving liver or kidney damage, including cyclohistidine-proline (CHP) or a food acceptable salt thereof as an active ingredient.
  • a health functional food for preventing or improving liver or kidney damage, including cyclohistidine-proline (CHP) or a food acceptable salt thereof as an active ingredient.
  • CHP cyclohistidine-proline
  • the agent for inducing liver or kidney toxicity may include at least one anticancer agent selected from the group consisting of cisplatin, gentamicin (GM) and acetaminophen (APAP); Or antibiotics.
  • Cytoprotective pharmaceutical composition containing cyclo histidine-proline (Cyclo His-Pro, CHP) of the present invention as an active ingredient has been found to inhibit the apoptosis of kidney cells or liver cells from toxicity, thereby preventing kidney and liver toxicity And compositions useful for the treatment.
  • FIG. 1 is a diagram showing the apoptosis inhibitory effect of GM-induced kidney cells (LLC-PK1 cells) of CHP: ** P ⁇ 0.01, *** P ⁇ 0.001.
  • CHP Cyclo His-Pro, GM; gentamicin.
  • Figure 2 is a diagram showing the apoptosis inhibitory effect of CHP APAP induced liver cells (Chang liver cells): * P ⁇ 0.05, *** P ⁇ 0.001.
  • CHP Cyclo His-Pro, APAP; acetaminophen.
  • Figure 3 is a graph of ALT measurement to determine the protective function of hepatotoxicity by cisplatin in the intake of CHP.
  • Figure 5 is a graph measuring the Creatinine intake of CHP to confirm the protective function of renal toxicity by cisplatin in mice.
  • Figure 6 is a graph measuring BUN intake of CHP to confirm the protective function of renal toxicity by cisplatin in mice.
  • the cell protective composition containing cyclo histidine-proline (Cyclo His-Pro, CHP) of the present invention as an active ingredient has an effect of inhibiting apoptosis of kidney cells or liver cells.
  • the present invention provides a composition for protecting cells containing cyclohistidine-proline (CHP) or a pharmaceutically acceptable salt thereof as an active ingredient.
  • CHP cyclohistidine-proline
  • the cyclo histidine-proline (CHP) may be isolated from the prostate extract (Prostate extract).
  • the present invention is a cytoprotective composition containing cyclohistidine-proline (CHP) or a pharmaceutically acceptable salt thereof as an active ingredient may protect the kidney cells or liver cells.
  • CHP cyclohistidine-proline
  • composition containing the cyclohistidine-proline (CHP) of the present invention as an active ingredient may be to inhibit apoptosis.
  • the composition of the present invention is to inhibit cell damage caused by the medicament
  • the medicament may be an anticancer agent or antibiotic, specifically, cisplatin, carboplatin, oxaliplatin and nedaplatin at least one platinum-based anticancer agent selected from the group consisting of (nedaplatin); Or antibiotics such as gentamicin or acetaminophen.
  • compositions of the present invention may further comprise suitable carriers, excipients or diluents commonly used in the manufacture of pharmaceutical compositions.
  • suitable carriers excipients or diluents commonly used in the manufacture of pharmaceutical compositions.
  • the content of the cyclohistidine-proline (CHP), salts, extracts or fractions thereof contained in the composition is not particularly limited, but is 0.0001 to 10% by weight, preferably 0.001 to 1% by weight based on the total weight of the composition. It may be prepared to contain%.
  • salts refers to a salt in a form that can be used pharmaceutically among salts in which a cation and an anion are bonded by an electrostatic attraction, and generally include a metal salt and an organic base. Salts, salts with inorganic acids, salts with organic acids, salts with basic or acidic amino acids, and the like.
  • the metal salt may be an alkali metal salt (sodium salt, potassium salt, etc.), alkaline earth metal salt (calcium salt, magnesium salt, barium salt, etc.), aluminum salt, or the like;
  • Salts with organic bases include triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N, N-dibenzylethylenediamine Salts and the like;
  • Salts with inorganic acids can be salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like;
  • Salts with organic acids can be salts with formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulf
  • composition of the present invention is preferably a pharmaceutical composition, wherein the pharmaceutical composition may be administered orally or parenterally, and during parenteral administration, external or intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection It is desirable to choose an injection or intrathoracic injection infusion.
  • the pharmaceutical composition according to the present invention may further include conventionally used excipients, disintegrants, sweeteners, lubricants, flavoring agents and the like.
  • the disintegrants include sodium starch glycolate, crospovidone, croscarmellose sodium, alginic acid, carboxymethyl cellulose calcium, sodium carboxymethyl cellulose, chitosan, guar gum, low-substituted hydroxypropyl cellulose, magnesium aluminum silicate, polyacryline Potassium and the like.
  • the pharmaceutical composition according to the present invention may further include a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, Calcium hydrogen phosphate, lactose, mannitol, malt, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, opadry, sodium starch glycolate, carnauba lead, synthetic aluminum silicate, stearic acid, magnesium stearate, Aluminum stearate, calcium stearate, sucrose, dextrose, sorbitol, talc and the like can be used.
  • the pharmaceutically acceptable additive according to the present invention is preferably included 0.1 to 90 parts by weight based on the pharmaceutical composition.
  • Solid preparations for oral administration include powders, granules, tablets, capsules, soft capsules, pills and the like.
  • Oral liquid preparations include suspensions, solvents, emulsions, syrups, and aerosols.In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.
  • Formulations for parenteral administration include powders, granules, tablets, capsules, sterile aqueous solutions, solutions, non-aqueous solutions, suspensions, emulsions, syrups, suppositories, aerosols, etc.
  • an external skin pharmaceutical composition of cream, gel, patch, spray, ointment, warning agent, lotion agent, linen agent, pasta agent or cataplasma agent may be prepared and used. It is not limited to this.
  • the non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used.
  • the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • the preferred dosage of the pharmaceutical composition of the present invention depends on the absorption rate, inactivation rate and excretion rate of the active ingredient in the body, the age, sex and condition of the patient, the severity of the disease to be treated, but may be appropriately selected by those skilled in the art. have.
  • oral dosages generally give an adult an amount of 0.0001 to 100 mg / kg of the pharmaceutical composition of the present invention per kg of body weight per day, preferably 0.001 to 100 mg / kg per day. Good to do. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect. Since the pharmaceutical composition of the present invention has little toxicity and side effects, it is a composition that can be used safely even when taken for a long time.
  • the pharmaceutical composition of the present invention has an excellent effect of protecting kidney cells, nephritis, acute pyelonephritis, chronic pyelonephritis, acute renal failure, tubulointerstitial fibrosis disorder, nephrotic syndrome, nephrogenic diabetes insipidus, electrolyte metabolic dyslipidemia, and It is possible to prevent or treat a disease selected from the group consisting of hypoNa + emia, and because it has an excellent effect of protecting liver cells, the disease is selected from the group consisting of liver failure, acute hepatitis, chronic hepatitis, cirrhosis, hepatic coma and alcoholic liver disease. It can be usefully used for prevention or treatment.
  • Cyclohistidine-proline of the present invention (Cyclo His-Pro, CHP) or a pharmaceutical thereof
  • a composition containing a salt acceptable as an active ingredient may be used as an anticancer adjuvant for preventing or treating liver or kidney toxicity caused by an anticancer agent.
  • the anticancer adjuvant is administered in combination with existing anticancer agents such as cisplatin, carboplatin, oxaliplatin, nedaplatin, doxorubicin, taxol, tamoxyphene, camptobel, addressyl, glibeck, etoposide, zometa, and silver corbin. Reducing kidney toxicity can improve anticancer efficacy.
  • the present invention provides a health functional food for preventing or improving liver or kidney damage, including cyclohistidine-proline (Cyclo His-Pro, CHP) or a food acceptable salt thereof as an active ingredient.
  • a health functional food for preventing or improving liver or kidney damage, including cyclohistidine-proline (Cyclo His-Pro, CHP) or a food acceptable salt thereof as an active ingredient.
  • the agent that causes liver or kidney injury may include at least one anticancer agent selected from the group consisting of cisplatin, gentamicin (GM) and acetaminophen (APAP); Or antibiotics.
  • at least one anticancer agent selected from the group consisting of cisplatin, gentamicin (GM) and acetaminophen (APAP); Or antibiotics.
  • the term “food acceptable salt” means a salt in a form that can be used in food, among salts in which cations and anions are bonded by an electrostatic attraction, and specific examples of the types thereof Includes examples of the above "pharmaceutically acceptable salts”.
  • the term "health food” refers to a food having an active health maintenance or promotion effect compared to a general food
  • a health supplement food refers to a food for health supplement purposes. Accordingly, the terms functional foods, health foods, health supplements are favorable,
  • the foods may be prepared in various forms such as tablets, capsules, powders, granules, liquids, pills, etc. to obtain a useful effect.
  • the term "functional food” is the same term as food for special health use (Food for special health use, FoSHU), in addition to the nutritional supply of the medical, medical effect is processed so that the bioregulatory function appears efficiently It means high food.
  • Food for special health use Food for special health use, FoSHU
  • Such a health functional food it is possible to manufacture a processed food that improves the shelf life at the same time using the composition to modify the characteristics of agricultural products, livestock products or aquatic products.
  • the health functional food of the present invention is excellent in protecting kidney cells, nephritis, acute pyelonephritis, chronic pyelonephritis, acute renal failure, tubulointerstitial fibrosis disorder, nephrotic syndrome, nephrogenic diabetes insipidus, electrolyte metabolic abnormalities hyperuricemia and It is possible to prevent or treat a disease selected from the group consisting of hypoNa + emia, and because it has an excellent effect of protecting liver cells, the disease is selected from the group consisting of liver failure, acute hepatitis, chronic hepatitis, cirrhosis, hepatic coma and alcoholic liver disease. It can be usefully used as a health food for prevention or improvement.
  • GM gentamicin
  • CHP cyclohistidine-proline
  • cyclohistidine-proline is prepared by requesting only a target spec (99% purity) from a peptide manufacturer (Bachem; Bubendorf, Switzerland). Gentamicin is available from Sigma Chemical Co. (St. Louis, MO, USA) and kidney cells (LLC-PK1 cells) were purchased from the American Type Culture Collection (ATCC; Manassas, VA, USA). Renal cells (LLC-PK1 cells) were incubated with CHP 0.1, 1, 5 or 10 mg / mL each with 5 mg / mL of GM simultaneously for 6 hours (FIG. 1A).
  • CHP 0.1, 1, 5 or 10 mg / mL each of the kidney cells were incubated for 2 hours after the pre-treatment for 2 hours, and further cultured for 4 hours by adding GM 5 mg / mL (Fig. 1B).
  • Cell viability was analyzed using a cell counting kit-8 (Dojindo Laboratories; Kumamoto, Japan) and measured with a microplate reader (Molecular Devices, LLC; Sunnyvale, CA, USA).
  • gentamicin induced apoptosis of kidney cells
  • CHP cyclo histidine-proline
  • GM gentamicin
  • CHP cyclo histidine-proline
  • APAP acetaminophen
  • CHP cyclohistidine-proline
  • acetaminophen is Sigma Chemical Co. (St. Louis, MO, USA) and Chang liver cells were purchased from the American Type Culture Collection (ATCC; Manassas, VA, USA). Chang liver cells were incubated with CHP 0.1, 1, 5 or 10 mg / mL each with simultaneous APAP 15 mM for 24 hours (FIG. 2A).
  • CHP 0.1, 1, 5 or 10 mg / mL each of the liver cells were incubated for 24 hours and then incubated for 24 hours further by adding 15 mM APAP (Fig. 2B).
  • Cell viability was analyzed using a cell counting kit-8 (Dojindo Laboratories; Kumamoto, Japan) and measured with a microplate reader (Molecular Devices, LLC; Sunnyvale, CA, USA).
  • acetaminophen induced apoptosis of liver cells
  • CHP Cyclo His-Pro
  • APAP acetaminophen
  • CHP Cyclo His-Pro
  • mice were purchased from Coatech Co., Ltd. and raised under constant conditions (temperature: 23 ⁇ 3 °C, relative humidity: 55 ⁇ 10%, daily cycle: 12 hours). It was. Five dogs were used as a group, and water and food were freely supplied from the cages. After the acclimation period, the experiment was conducted as shown in Table 1 divided into five groups.
  • Group 1 was set as negative control group by ingesting water
  • group 2 was set as liver damage control group by cisplatin administration after drinking water
  • group 3 was negative intake of CHP 1 mg / L
  • group 4 was CHP 5 mg.
  • group 5 was set to a group of protective effects of liver damage due to cisplatin administration a week after the intake of CHP 10 mg / L. Negative water supplied to CHP was replaced once every two days.
  • CHP was first administered to mice by concentration for 1 week, and then cisplatin was administered and liver function was checked after 24 hours.
  • ALT and AST blood was collected by abdominal aortic blood collection from a mouse, and then serum was separated using a centrifuge, and then measured using an automatic analyzer (Hitachi 7180; Tokyo, Japan).
  • the pharmaceutical composition containing CHP as an active ingredient has a superior effect of protecting liver cells, disease caused by liver disease It can be seen that it can be usefully used for the prevention or treatment of.
  • ICR mice In order to measure the renal toxicity protection effect of mice by cyclohistidine-proline (CHP), ICR mice were purchased from Coatech Co., Ltd. under constant conditions (temperature: 23 ⁇ 3 °C, relative humidity: 55 ⁇ 10%, daily cycle). : 12 hours). Five dogs were used as a group, and water and food were freely supplied from the cages. After the acclimation period, the experiment was conducted as shown in Table 1 divided into three groups.
  • CHP cyclohistidine-proline
  • Cisplatin mg / kg
  • Cisplatin mg / kg
  • term Normal Control - - Daily oral administration of CHP for 1 week followed by intraperitoneal injection of Cisplatin 10 mg / kg 2.
  • Cisplatin control - 10 3.
  • Group 1 was set as a negative control group by oral administration of water
  • group 2 was set as a renal damage control group by cisplatin administration after oral administration of water
  • group 3 was orally administered daily for 1 week at 1 mg / kg CHP. Kidney damage protection group due to cisplatin administration was set.
  • cyclohistidine-proline (CHP) on kidney function
  • creatinine blood was collected from the mouse heart, and then serum was separated using a centrifuge. Then, the biochemical analysis equipment (BS-390, Mindray Bio-Medical Electronics Co., Ltd., China) was used. Measured. The results are shown in FIG. The experimental results were verified by the t-test between the cisplatin-treated liver injury group and the other experimental group, and showed a statistically significant difference (#p ⁇ 0.05, ## p ⁇ 0.005).
  • the pharmaceutical composition comprising cyclohistidine-proline (CHP) as an active ingredient shows an excellent effect of reducing the concentration of creatinine which can confirm the blood renal function level of cyclo histidine-proline (CHP). Since it is excellent in protecting the kidney cells, it can be seen that it can be useful for the prevention or treatment of diseases consisting of kidney disease.
  • CHP cyclohistidine-proline
  • mice In order to measure the renal toxicity protection effect of mice by cyclo histidine-proline (CHP), ICR mice were purchased from Coatech Co., Ltd. : 12 hours). Five dogs were used as a group, and water and food were freely supplied from the cages. After the acclimation period, the experiment was conducted as shown in Table 1 divided into three groups.
  • CHP cyclo histidine-proline
  • Cisplatin mg / kg
  • Cisplatin mg / kg
  • Group 1 was set as a negative control group by oral administration of water
  • group 2 was set as a kidney damage control group by cisplatin administration after oral administration of water
  • group 3 was orally administered daily with oral administration for 1 week at 1 mg / kg CHP. Kidney damage protection group due to cisplatin administration was set.
  • cyclohistidine-proline (CHP)
  • BUN blood was collected from a mouse heart, and then serum was separated using a centrifuge, and then measured using a biochemical analysis device (BS-390, Mindray Bio-Medical Electronics Co., Ltd., China).
  • the test result was verified by performing t-test between the cisplatin-induced liver injury group and another experimental group, and showed a statistically significant difference (#p ⁇ 0.05).
  • cyclohistidine-proline shows an excellent effect of reducing the concentration of Bun, the blood urea nitrogen that can confirm the blood kidney function level, the pharmaceutical composition containing CHP as an active ingredient to protect kidney cells Since it is excellent it can be seen that it can be useful for the prevention or treatment of diseases consisting of kidney disease.
  • CHP according to the present invention has confirmed that it has an excellent effect of inhibiting and reducing liver and kidney damage caused by cisplatin, an anticancer agent, and thus a pharmaceutical composition or health functional food for the prevention and treatment of liver and kidney toxic diseases caused by the anticancer agent. It can be usefully used as.

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Abstract

La présente invention concerne une composition pharmaceutique pour la protection des cellules contenant de la cyclo-histidine-proline (cyclo His-Pro, CHP) en tant qu'ingrédient actif. La composition pharmaceutique pour la protection des cellules contient de la cyclo-histidine-proline (CHP) en tant qu'ingrédient actif de la présente invention, possède un excellent effet de protection des cellules rénales et des cellules hépatiques contre la toxicité, et peut donc être avantageusement utilisé pour la prévention ou le traitement de maladies rénales et hépatiques.
PCT/KR2017/007518 2016-07-13 2017-07-13 Composition pour la protection des cellules contenant de la cyclo-histidine-proline comme ingrédient actif WO2018012901A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP20206943.1A EP3797788A1 (fr) 2016-07-13 2017-07-13 Composition pour la protection des cellules hepatiques contenant de la cyclo-histidine-proline comme ingrédient actif
US16/316,595 US10918693B2 (en) 2016-07-13 2017-07-13 Composition for cell protection containing cyclo histidine-proline as active ingredient
CN202110619829.XA CN113368248B (zh) 2016-07-13 2017-07-13 包含环组氨酸-脯氨酸作为有效成分的用于保护细胞的组合物
JP2019501912A JP6750087B2 (ja) 2016-07-13 2017-07-13 シクロヒスチジン−プロリンを有効成分として含む細胞保護用組成物
EP17827971.7A EP3486252B1 (fr) 2016-07-13 2017-07-13 Composition pour la protection des cellules rénales contenant de la cyclo-histidine-proline comme ingrédient actif
CN201780042925.4A CN109476701B (zh) 2016-07-13 2017-07-13 包含环组氨酸-脯氨酸作为有效成分的用于保护细胞的组合物
US17/172,879 US11433114B2 (en) 2016-07-13 2021-02-10 Composition for cell protection containing cyclo histidine-proline as active ingredient
US17/856,729 US11890317B2 (en) 2016-07-13 2022-07-01 Cell-protecting composition containing cyclo histidine-proline as active ingredient

Applications Claiming Priority (4)

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KR20160088751 2016-07-13
KR10-2016-0088751 2016-07-13
KR10-2017-0088341 2017-07-12
KR1020170088341A KR102012554B1 (ko) 2016-07-13 2017-07-12 사이클로 히스티딘-프롤린을 유효성분으로 포함하는 세포 보호용 조성물

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US17/172,879 Division US11433114B2 (en) 2016-07-13 2021-02-10 Composition for cell protection containing cyclo histidine-proline as active ingredient

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2022528087A (ja) * 2019-03-28 2022-06-08 ノブメタファーマ カンパニー リミテッド 線維症の予防、改善または治療のためのｃｈｐ（シクロ－ヒスプロ）の用途
JP2022528857A (ja) * 2019-03-28 2022-06-16 ノブメタファーマ カンパニー リミテッド 腹膜線維症の予防、改善または、治療のためのｃｈｐ（シクロ－ヒスプロ）の用途
JP7224006B2 (ja) 2019-03-28 2023-02-17 ノブメタファーマ カンパニー リミテッド 腹膜線維症の予防、改善または、治療のためのｃｈｐ（シクロ－ヒスプロ）の用途
JP7330471B2 (ja) 2019-03-28 2023-08-22 ノブメタファーマ カンパニー リミテッド 線維症の予防、改善または治療のためのｃｈｐ（シクロ－ヒスプロ）の用途

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