[go: up one dir, main page]

WO2012085321A1 - Utilisation de la l-carnitine et de ses compositions pour le traitement et la prévention des atteintes rénales - Google Patents

Utilisation de la l-carnitine et de ses compositions pour le traitement et la prévention des atteintes rénales Download PDF

Info

Publication number
WO2012085321A1
WO2012085321A1 PCT/ES2011/070895 ES2011070895W WO2012085321A1 WO 2012085321 A1 WO2012085321 A1 WO 2012085321A1 ES 2011070895 W ES2011070895 W ES 2011070895W WO 2012085321 A1 WO2012085321 A1 WO 2012085321A1
Authority
WO
WIPO (PCT)
Prior art keywords
wln
renal
composition
carnitine
wlnlc
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/ES2011/070895
Other languages
English (en)
Spanish (es)
Inventor
Carmen María VÁZQUEZ CUETO
Antonio Jesús BLANCA LOBATO
Sonia ZAMBRANO SEVILLA
María Victoria RUIZ ARMENTA
José Luis MIGUEL CARRASCO
María Teresa MONSERRAT GARCÍA
José Luis ARIAS JIMÉNEZ
Óscar ARAMBURU BODAS
Alfonso Mate Barrero
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Universidad de Sevilla
Servicio Andaluz de Salud
Original Assignee
Universidad de Sevilla
Servicio Andaluz de Salud
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Universidad de Sevilla, Servicio Andaluz de Salud filed Critical Universidad de Sevilla
Publication of WO2012085321A1 publication Critical patent/WO2012085321A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system

Definitions

  • L-carnitine Use of L-carnitine and its compositions, for the treatment and prevention of kidney damage.
  • the present invention is within the field of Medicine and Nutrition, and refers to the use of L-carnitine (LC), for the preparation of a medicament, pharmaceutical composition or nutritional supplement aimed at combating nephropathy, based on improving the parameters of oxidative stress and inflammatory markers, exercising in turn a nephroprotective character that could prevent the development of kidney disease, and especially that associated with arterial hypertension (HT).
  • LC L-carnitine
  • HT ulcerative colitis
  • L-Carnitine L-3-hydroxy-4-N, N, N-trimethylaminobutyrate
  • LC L-3-hydroxy-4-N, N, N-trimethylaminobutyrate
  • the main function of this amino acid derivative is to act as a cofactor in the transport of fatty acids into the mitochondria, where ⁇ - is produced. Oxidation thereof, to obtain metabolic energy (Bremer J. Physiol Rev 1983; 63: 1420-1480), playing a crucial role in the metabolism of fatty acids. 75% of the amount of LC required by the body comes from the diet. The rest is synthesized endogenously in the liver, kidney and brain, from the amino acids lysine and methionine (Tanphaichitr and col. J Biol Chem 1973; 248: 2176-2181).
  • LC is not normally considered as an essential nutrient, because the organism under standard conditions makes it possible to synthesize the necessary amounts.
  • This deficiency appears in some cardiovascular pathologies (Ferrari and col. Ann NY Acad Sci 2004; 033: 79-91; Kendier BS J Cardiovasc Nurs 2006; 21: 9-16), as well as in hemodialysis patients, where a large loss is observed from LC (Hedayati SS. Semin Dial 2006; 8: 323-328).
  • the kidney is an essential organ in LC homeostasis, since more than 95% of the filtered LC is reabsorbed by its tubules (Lahjouji and col. Mol Genet and Metabol 2001; 73, 287-297), by This fact, together with its role as an organ that produces LC, indicates that renal damage caused by arterial hypertension (AHT) could lead to a lack of LC in the body.
  • AHT arterial hypertension
  • GFR glomerular filtration rate
  • High Risk Factors e.g., glucose
  • Renal damage e.g., presence of more than 90
  • Kidney damage has various etiologies, and various pathophysiological mechanisms contribute to the development and progression of kidney damage. It is important to find compounds that prevent kidney damage, with few side effects, and that can be administered as usual, for example, included in food, in the diet.
  • a first aspect of the invention relates to the use of L-carnitine, of formula (I):
  • the term “derivative” includes both pharmaceutically acceptable compounds, that is, derivatives of the compound of formula (I) that can be used in the manufacture of a medicament, as pharmaceutically unacceptable derivatives, since these they may be useful in the preparation of pharmaceutically acceptable derivatives.
  • the prodrugs of the compounds of formula (I) include any compound derived from a compound of formula (I), for example, esters, including carboxylic acid esters, amino acid esters, phosphate esters, metal salt sulphonate esters, etc., carbamates, amides, etc., which, when administered to an individual, is capable of providing, directly or indirectly, said compound of formula (I) in said individual.
  • said derivative is a compound that increases the bioavailability of the compound of formula (I) when administered to an individual or that enhances the release of the compound of formula (I) in a biological compartment.
  • the nature of said derivative is not critical as long as it can be administered to an individual and provides the compound of formula (I) in a biological compartment of an individual.
  • the preparation of said prodrug can be carried out by conventional methods known to those skilled in the art.
  • renal damage in the present invention we refer, without limitation, to any functional or structural abnormality of different etiology either by a decrease in renal or intrarenal perfusion, by a toxic aggression or obstruction of the renal tubule, by tubulointerstitial inflammation and edema or by a reduction in the filtration capacity of the glomerulus.
  • renal damage is chronic renal damage.
  • the L-carnitine, or its salts, prodrugs, derivatives or the like can be administered in a substantially pure form to a mammal, and preferably a human, or can be administered as part of a more complex composition.
  • the amount of L-carnitine, or its salts, prodrugs, derivatives or the like is such that it achieves the desired effect, thus being an effective amount.
  • mixtures that these compounds may contain are, but are not limited to, dried plant extracts, cocoa powder, dehydrated food, etc.
  • dietary matrices are, but not limited to: milk, yogurt, cheese, fermented milk, soy milk, pre-cooked cereals, cookies, bread, rolls, butter, margarine, sausages, frying oils, vegetable oils, olive oil , palm oil, soybean oil, sunflower oil, condiments, fruit juices, syrups, ice cream, frozen products, chewing gums, and intermediate foods.
  • composition of the invention comprising L-carnitine, or its salts, prodrugs, derivatives or the like, for the prevention or treatment of kidney damage .
  • composition of the invention also refers to a composition comprising L-carnitine, or any of its salts, prodrugs, derivatives or the like, or any combination thereof, for use in the prevention or treatment of kidney damage.
  • kidney damage In a preferred embodiment it refers to the prevention of kidney damage. In another preferred embodiment it refers to the use of the composition in the preparation of a medicament for the prevention of renal damage. In a more preferred embodiment of the present invention, renal damage is chronic renal damage.
  • the composition of the invention is a food composition. More preferably, the food composition includes a nutritional supplement. Even more preferably, it further comprises suitable vehicles, such as diluents, adjuvants, excipients or vehicles in which L-carnitine is administered, or any of its salts, prodrugs, derivatives or analogs, or combinations thereof.
  • suitable vehicles such as diluents, adjuvants, excipients or vehicles in which L-carnitine is administered, or any of its salts, prodrugs, derivatives or analogs, or combinations thereof.
  • the composition of the invention is a pharmaceutical composition.
  • the pharmaceutical composition further comprises a pharmaceutically acceptable carrier. In another preferred embodiment, it also comprises another active ingredient.
  • medication refers to any substance used for prevention, diagnosis, relief, treatment or cure of diseases in man and animals.
  • the disease is renal damage, and more preferably it is chronic renal damage.
  • active substance means any component that potentially provides a pharmacological activity or other different effect on the diagnosis, cure, mitigation, treatment, or prevention of a disease, or that affects the structure or function of the body of man or other animals.
  • the term includes those components that promote a chemical change in the preparation of the drug and are present therein in a modified form intended to provide the specific activity or effect.
  • compositions of the present invention can be formulated for administration to an animal, and more preferably to a mammal, including man, in a variety of ways known in the state of the art.
  • they can be, without limitation, in sterile aqueous solution or in biological fluids, such as serum.
  • Aqueous solutions may be buffered or unbuffered and have additional active or inactive components. Additional components include salts to modulate ionic strength, preservatives including, but not limited to, antimicrobial agents, antioxidants, chelators, and the like, and nutrients including glucose, dextrose, vitamins and minerals.
  • the compositions can be prepared for administration in solid form.
  • compositions may be combined with various inert vehicles or excipients, including but not limited to; binders such as microcrystalline cellulose, gum tragacanth, or gelatin; excipients such as starch or lactose; dispersing agents such as alginic acid or corn starch; lubricants such as magnesium stearate, glidants such as colloidal silicon dioxide; sweetening agents such as sucrose or saccharin; or flavoring agents such as peppermint or methyl salicylate.
  • binders such as microcrystalline cellulose, gum tragacanth, or gelatin
  • excipients such as starch or lactose
  • dispersing agents such as alginic acid or corn starch
  • lubricants such as magnesium stearate, glidants such as colloidal silicon dioxide
  • sweetening agents such as sucrose or saccharin
  • flavoring agents such as peppermint or methyl salicylate.
  • compositions and / or their formulations can be administered to an animal, including a mammal and, therefore, to man, in a variety of ways, including, but not limited to, intraperitoneal, intravenous, intramuscular, subcutaneous, intracecal, intraventricular, oral, enteral, parenteral, intranasal or dermal.
  • the route of administration is oral.
  • the dosage to obtain a therapeutically effective amount depends on a variety of factors, such as the age, weight, sex, tolerance, ... of the mammal.
  • the term “therapeutically effective amount” refers to the amount of L-carnitine, or its salts, prodrugs, derivatives or analogs, or combinations thereof, that produce the desired effect and, in general , will be determined, among other causes, by the characteristics of said prodrugs, derivatives or analogues and the therapeutic effect to be achieved.
  • the "adjuvants” and “pharmaceutically acceptable carriers” that can be used in said compositions are the vehicles known to those skilled in the art.
  • excipient refers to a substance that aids the absorption, distribution or action of any of the active ingredients of the present invention, stabilizes said active substance or aids in the preparation of the medicament in the sense of giving it consistency or providing flavors. Make it more enjoyable.
  • the excipients could have the function of keeping the ingredients together such as starches, sugars or cellulose, sweetening function, dye function, drug protection function such as to isolate it from air and / or moisture, function filling a tablet, capsule or any other form of presentation such as dibasic calcium phosphate, a disintegrating function to facilitate the dissolution of the components and their absorption in the intestine, without excluding other types of excipients not mentioned in this paragraph.
  • pharmaceutically acceptable excipient refers to the excipient being allowed and evaluated so as not to cause damage to the organisms to which it is administered.
  • the excipient must be pharmaceutically suitable, that is, an excipient that allows the activity of the active ingredient or of the active ingredients, that is, that is compatible with the active ingredient, in this case, the active ingredient is any of the compounds of the present invention.
  • a “pharmaceutically acceptable carrier” refers to those substances, or combination of substances, known in the pharmaceutical sector, used in the preparation of pharmaceutical forms of administration and includes, but are not limited to, solids, liquids, solvents or surfactants.
  • the vehicle like the excipient, is a substance that is used in the medicament to dilute any of the compounds of the present invention to a certain volume or weight.
  • the pharmaceutically acceptable carrier is an inert substance or action analogous to any of the cells of the present invention.
  • the function of the vehicle is to facilitate the incorporation of other compounds, allow a better dosage and administration or give consistency and form to the pharmaceutical composition.
  • the pharmaceutically acceptable carrier is the diluent.
  • the invention was carried out by designing a prospective experimental study, in which we will use rats of the Wistar strain, randomly assigned to the following groups:
  • the animal is placed in metabolism cages for 24 hours with the intention of obtaining urine for protein determination. Subsequently, the animal's weight is obtained and slaughtered with a lethal dose of pentobarbital. The kidneys are removed, cleaned and the capsule is removed. The renal cortex is then sectioned and frozen by immersion in liquid nitrogen and kept at -80 ° C until the moment of use. Part of this renal cortex is homogenized to determine the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR), using commercial kits based on spectrophotometric techniques.
  • SOD superoxide dismutase
  • GPx glutathione peroxidase
  • GR glutathione reductase
  • NADPH oxidase by chemiluminescence techniques.
  • the rest of the renal cortex is used to determine, by means of the real-time PCR technique, the gene expression of proinflammatory cytokines (interleukin 6, IL-6 and interleukin 1 ⁇ , I L-1 ⁇ ) and anti-inflammatory (interleukin 1 0, IL-10); of the Nox4 and p22phox subunits of the enzyme NADPH oxidase; of the angiotensin converting enzyme (ACE); and of the AT1 receptor of angiotensin II.
  • proinflammatory cytokines interleukin 6, IL-6 and interleukin 1 ⁇ , I L-1 ⁇
  • anti-inflammatory interleukin 1 0, IL-10
  • Table I shows the values (mm Hg) for diastolic and systolic blood pressures at the end of treatment in the four experimental groups of animals, together with proteinuria values expressed in mg of protein / 24 h / 100g body weight (mean ⁇ standard error).
  • Table II shows the activity values of the enzyme superoxide dismutase (SOD) (U / g, units per gram of protein) in renal cortex of the four experimental groups of animals (mean ⁇ standard error). Once the ANOVA test was performed, a p ⁇ 0.0001 was obtained. Applying the analysis by Tukey test, the following meanings were obtained for SOD:
  • Table III shows the activity values of the enzyme glutathione peroxidase (GPx) (U / g, units per gram of protein) in renal cortex of the four experimental groups of animals (mean ⁇ standard error).
  • Table IV shows the activity values of the enzyme glutathione reductase (GR) (U / g) in renal cortex of the four experimental groups of animals (mean ⁇ standard error).
  • Table V shows the values of the activity of the enzyme NADPH oxidase (LRU, relative units of light) in the renal cortex of the four experimental groups of animals (mean ⁇ standard error). Once the ANOVA test was performed, a p ⁇ 0.0001 was obtained. Applying the analysis by Tukey test, the following meanings were obtained for NADPH oxidase:
  • Table VI shows the values of the relative gene expression of Nox 4, in renal cortex of the four experimental groups of animals (mean ⁇ standard error).
  • Table VII shows the values for the relative gene expression of p22 phox, in renal cortex of the four experimental groups of animals (mean ⁇ standard error).
  • Table VIII shows the values for the relative gene expression of IL-6, in renal cortex of the four experimental groups of animals (mean ⁇ standard error). Once the ANOVA test was performed, a p ⁇ 0.0001 was obtained. Applying the analysis by Tukey test, the following meanings were obtained for the relative expression of IL-6:
  • Table IX shows the values for the relative gene expression of IL-1 ⁇ , in renal cortex of the four experimental groups of animals (mean ⁇ standard error).
  • WISTAR- WLN p ⁇ 0.001
  • WLN- WLNLC p ⁇ 0.001
  • Table XI shows the relative gene expression of ACE, in renal cortex of the four experimental groups of animals (mean ⁇ standard error).
  • WLN-WLNLC p ⁇ 0.001
  • Table XII shows the relative gene expression of AT1, in renal cortex of the four experimental groups of animals (mean ⁇ standard error).
  • NAD PH oxidase is only significant after treatment with L-NAME and the simultaneous supply of LC reverses this activity, normalizing it.
  • the treatment with L-NAME considerably increases the gene expression of two subunits of NADPH oxidase, Nox4 and p22 phox, reaching normal values after simultaneous delivery of LC.
  • the gene expressions of the ACE and the AT1 receptor increase significantly in rats treated with L-NAME with respect to the values found in normotensive rats, with normal levels observed after treatment with LC.
  • treatment with L-NAME produces an increase in systolic and diastolic blood pressure measurements and proteinuria values, an increase that is attenuated, in case of arterial pressures and disappears, in case of proteinuria, with the simultaneous administration of LC.
  • the simultaneous treatment with L-NAME and LC has reduced the effects that oxidative stress caused in the renal cortex of rats treated with L-NAME, through its action on antioxidant enzymes and the activity of the NADPH oxidase enzyme, confirming the antioxidant effects of LC in the kidney of hypertensive rats.
  • the joint treatment with L-NAME and LC also had remarkable effects on the gene expression of pro-inflammatory and anti-inflammatory interleukins, showing the anti-inflammatory effects of LC in the kidney of hypertensive rats.
  • the LC exerts, in part, its antioxidant and anti-inflammatory nephroprotective action acting on the renin angiotensin system, as shown by the gene expression values for ACE and AT1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne l'utilisation de L-carnitine ou de tout sel, dérivé ou analogue de celle-ci, ou de toute combinaison de ceux-ci, et des compositions alimentaires et pharmaceutiques les contenant, pour la préparation de compositions alimentaires et/ou pharmaceutiques destinées à la prévention ou au traitement des atteintes rénales.
PCT/ES2011/070895 2010-12-22 2011-12-22 Utilisation de la l-carnitine et de ses compositions pour le traitement et la prévention des atteintes rénales Ceased WO2012085321A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES201031914A ES2385169B1 (es) 2010-12-22 2010-12-22 Uso de la l-carnitina y sus composiciones, para el tratamiento y la prevención del daño renal.
ES201031914 2010-12-22

Publications (1)

Publication Number Publication Date
WO2012085321A1 true WO2012085321A1 (fr) 2012-06-28

Family

ID=46313224

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/ES2011/070895 Ceased WO2012085321A1 (fr) 2010-12-22 2011-12-22 Utilisation de la l-carnitine et de ses compositions pour le traitement et la prévention des atteintes rénales

Country Status (2)

Country Link
ES (1) ES2385169B1 (fr)
WO (1) WO2012085321A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN120130576A (zh) * 2025-03-21 2025-06-13 华润爱生动物保健(江苏)有限公司 左旋肉碱作为猫科动物aim蛋白激活剂的用途以及用于猫科动物改善肾功能的用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001007039A2 (fr) * 1999-07-28 2001-02-01 Sigma-Tau Healthscience S.P.A. Composition pour prevenir et traiter les affections et les maladies du rein
WO2001007038A2 (fr) * 1999-07-27 2001-02-01 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Utilisation de l-carnitine et de ses derives alkanoyles pour preparer un medicament destine a traiter les patients atteints de nephropathie diabetique et/ou dysmetabolique

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001007038A2 (fr) * 1999-07-27 2001-02-01 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Utilisation de l-carnitine et de ses derives alkanoyles pour preparer un medicament destine a traiter les patients atteints de nephropathie diabetique et/ou dysmetabolique
WO2001007039A2 (fr) * 1999-07-28 2001-02-01 Sigma-Tau Healthscience S.P.A. Composition pour prevenir et traiter les affections et les maladies du rein

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CAYIR, KERIM ET AL.: "Protective effect of L-carnitine against cisplatin-induced liver and kidney oxidant injury in rats", CENTRAL EUROPEAN JOURNAL OF MEDICINE, vol. 4, no. 2, 2009, pages 184 - 191, XP055100152 *
SENER, G. ET AL.: "L-Carnitine ameliorates oxidative damage due to chronic renal failure in rats", J. CARDIOVASC. PHARMACOL., vol. 43, no. 5, May 2004 (2004-05-01), pages 698 - 705, XP055100150 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN120130576A (zh) * 2025-03-21 2025-06-13 华润爱生动物保健(江苏)有限公司 左旋肉碱作为猫科动物aim蛋白激活剂的用途以及用于猫科动物改善肾功能的用途

Also Published As

Publication number Publication date
ES2385169A1 (es) 2012-07-19
ES2385169B1 (es) 2013-09-23

Similar Documents

Publication Publication Date Title
EP3628640B1 (fr) Procédés de fabrication d'une molécule deutérée ou non-deutérée et formulations pharmaceutiques pour traitement
ES2382115T3 (es) Formulación oral con efectos cardiovasculares beneficiosos, que comprende berberina
JP6903594B2 (ja) 食品、栄養補助食品、化粧品および医薬品に有用な複数の相乗的抗酸化活性を示すフィトコンプレックス
US9226937B2 (en) Compositions containing resveratrol and nucleotides
KR20120060945A (ko) 환경대사적 전환인자, 다차원 세포내 분자 또는 환경적 영향인자를 사용한 대사적 장애의 치료 방법
CA2801224A1 (fr) Formulations alimentaires
ES2668525T3 (es) Composición farmacéutica antihipóxica y su aplicación
US20230117757A1 (en) Coenzyme q production accelerator and method for accelerating coenzyme q production
CN119097620A (zh) 具有改善的生物利用度的中链甘油三酯制剂及其有关方法
JP2004520341A (ja) 血圧低下効果を有する機能製品中のベタインの使用
KR102686466B1 (ko) 티로신을 유효성분으로 함유하는 단백질 내 티로신의 니트로화에 의한 질환의 예방, 개선 또는 치료용 조성물
WO2012085321A1 (fr) Utilisation de la l-carnitine et de ses compositions pour le traitement et la prévention des atteintes rénales
KR20080097437A (ko) 혈압 정상화 조성물
US10314814B2 (en) Composition comprising 7-hydroxymatairesinol
WO2016132483A1 (fr) Inhibiteur de chymase humaine et médicament pour prévenir et traiter une maladie associée à une activité de chymase humaine
ES2394906B1 (es) Uso de la l-carnitina y sus composiciones para el tratamiento y la prevención de la fibrosis renal.
EA035709B1 (ru) Фармацевтическая композиция для улучшения состояния при хронической почечной недостаточности или предотвращения ее прогрессирования
JP5723276B2 (ja) コレステロールエステル転送タンパク質阻害剤
US20220241235A1 (en) Composition comprising citrate and carnitine able to activate the production of the protein klotho
US10391114B2 (en) Therapeutic combinations of curcuminoids and flavonoids
IT201900018089A1 (it) Associazione per l’uso nel trattamento e prevenzione di ischemia cerebrale e successiva riperfusione
Ün et al. Protective effects of phloretin and phloridzin on indomethacin-induced gastric ulcers in mice: characterization of potential molecular mechanisms
ES2392879B1 (es) Composiciones y preparaciones combinadas de sunitinib y l-carnitina
WO2013083867A1 (fr) Prévention et traitement des lésions rénales associées à la lithiase rénale des voies urinaires
TWI643632B (zh) 蘆筍葉萃取物、其製備方法及其用途

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11852084

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11852084

Country of ref document: EP

Kind code of ref document: A1