WO2012085785A1 - Combinación y composición para el tratamiento de obesidad - Google Patents
Combinación y composición para el tratamiento de obesidad Download PDFInfo
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- WO2012085785A1 WO2012085785A1 PCT/IB2011/055723 IB2011055723W WO2012085785A1 WO 2012085785 A1 WO2012085785 A1 WO 2012085785A1 IB 2011055723 W IB2011055723 W IB 2011055723W WO 2012085785 A1 WO2012085785 A1 WO 2012085785A1
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- Prior art keywords
- orlistat
- resveratrol
- pharmaceutically acceptable
- combination
- acceptable salts
- Prior art date
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/205—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings
- C07C39/21—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings with at least one hydroxy group on a non-condensed ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/02—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D305/04—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/02—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D305/10—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having one or more double bonds between ring members or between ring members and non-ring members
- C07D305/12—Beta-lactones
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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
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/332—Promoters of weight control and weight loss
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Definitions
- the present invention has its application in the pharmaceutical field, especially in the field of combinations and pharmaceutical compositions comprising a lipase inhibitor, a phytoalexin and pharmaceutically acceptable carriers or excipients.
- the present invention also relates to a process for the manufacture of the pharmaceutical composition and the use of said composition for the preparation of a medicament useful in the treatment of overweight, obesity and related health problems.
- the World Health Organization (WHO) warns that there are more than 1, 600 million overweight people in the world and that this figure increases exponentially. According to WHO, the number of people with obesity amounts to more than 700 million.
- Obesity is a chronic and degenerative disease. In adults, overweight and obesity promote the development of diseases such as hypertension, diabetes mellitus, gout, stroke, heart disease and others. Some scientific research ensures that current childhood obesity will cause in the coming years a greater growth of the population of young adults with diabetes mellitus, hypertension, hyperlipidemias and many others problems related to excess body fat and sedentary life.
- the risk of developing type 2 diabetes increases by 20% in overweight or obese people.
- a body mass index (normal BMI 18.5-24.9) equal to or greater than 25 is associated with an increased risk of bone and hip fractures.
- the main therapy that should be considered is the improvement in the patient's habits, that is, increasing exercise and eating a proper diet.
- treatment is required.
- pharmacological Most drugs for the treatment of obesity act by decreasing food intake by an appetite suppression mechanism. These drugs act at the level of the central nervous system (CNS) and have an anorexigenic effect. For this reason its use in long-term treatments is not recommended.
- CNS central nervous system
- the ideal characteristics of a drug for the treatment of obesity are:
- Adrenergic Diethylpropion, Mazindol, Phentermine, Ephedrine.
- Fat absorption inhibitor or lipase enzyme inhibitor Orlistat.
- the active agent orlistat belongs to the group of lipase enzyme inhibitors. This compound is a white to off-white waxy solid, easily soluble in chloroform, insoluble in water, with a melting point between 40 ° C-48 ° C.
- Orlistat decreases the absorption of fat by inhibiting the activity of pancreatic lipase avoiding the splitting of fats into its simplest components, causing them to be eliminated without being absorbed.
- This compound exerts its therapeutic activity in the lumen of the stomach and in the small intestine, forming a covalent bond with the serine at the active site of gastric and pancreatic lipases.
- Orlistat is administered orally at doses not greater than 360 mg per day since higher doses do not have a therapeutic effect.
- different doses can be administered, which can be from 30 mg, 60 mg, 120 mg and up to 240 mg.
- Different medical publications mention that the usual dose is the administration of 120 mg three times a day.
- orlistat In obese patients with type 2 diabetes, orlistat is used in weight reduction, and consequently, it helps better glycemic control and attenuates postprandial increases in triglycerides, cholesterol and free fatty acids. Orlistat provides additional control when administered in combination with antidiabetic agents such as metformin, sulfonylureas and / or insulin.
- antidiabetic agents such as metformin, sulfonylureas and / or insulin.
- Plasma concentrations of intact orlistat were virtually undetectable ( ⁇ 5 ng / ml) after single administration of 360 mg. In general, the Plasma concentrations are extremely low ( ⁇ 10 ng / ml or 0.02 ⁇ ), with no evidence of accumulation. Studies in people with normal or obese weights have shown that fecal excretion of the non-absorbed drug was the main route of elimination. Approximately 97% of the administered dose was excreted in feces and 83% of that was unaltered orlistat.
- Adverse reactions with orlistat are largely gastrointestinal in nature and are related to the pharmacological effect of the drug in the 30% decrease in the absorption of ingested fat. Commonly observed events are fat spots, flatulence and secretion, fecal urgency, feces with fat / oil, oily evacuation, increased defecation and fecal incontinence. A higher incidence of these effects has been observed at a higher fat content in the diet.
- resveratrol (3,5,4'-trihydroxystilbene) is a phytoalexin present in grapes and derived products such as wine, and in others foods like oysters, peanuts and nuts. It is a potent antioxidant, polyphenolic, with molecular formula C 14 H 12 O 3 and molecular weight 228.24. It is a yellowish white powder, non-hygroscopic, insoluble in water, soluble in alcohol and methanol, insoluble in 10% hydrochloric acid and photosensitive. It is found in nature in the form of a cis- and trans isomer, the trans-resveratrol present in the grape skin being the most common form.
- this active agent is not yet defined, although some publications mention that it is capable of stimulating the family of SIRT1 genes, which encode sirtuins (NAD-dependent histone deacetylases), starting up the metabolic processes related to the duration of life, which are the same that are triggered by hypocaloric regimes, thereby mimicking caloric restriction. Thus, it is assumed that a diet low in calories and carbohydrates is capable of extending life. Resveratrol is able to inhibit several anti-inflammatory enzymes, including cyclooxygenase and lipoxygenase.
- resveratrol In metabolic regulation, resveratrol allows maintaining the effects of a hypocaloric diet, without changing food intake, and may be beneficial in the treatment of obesity.
- resveratrol In animal studies, resveratrol exhibits anti-aging, cardioprotective effects (in vitro resveratrol inhibits platelet aggregation), neuroprotective (activating SIRT1 reduces neurodegenerative diseases), anti-inflammatory, chemopreventive and as a metabolic regulator maintains a hypocaloric diet, without vary food intake and may be beneficial in the treatment of obesity.
- trans-resveratrol seems to be well absorbed when ingested orally, its bioavailability is relatively low due to its rapid metabolism and renal elimination (approximate half-life of 8 hours) achieving very low levels, both intracellular, as well as in plasma
- This active agent is removed in its conjugated forms glucoronate and sulfonate.
- Studies have shown a polymorphism in intestinal absorption, as well as in hepatic metabolization according to the species used in the studies.
- Patent application WO 2001/000205 describes the combination of sibutramine and orlistat. This combination may represent a risk for patients since sibutramine has been withdrawn from the market by health authorities, due to the adverse cardiovascular effects it causes.
- MX / a / 2007/006092 describes the use of orlistat with simvastatin or atorvastatin, to lower lipid or fatty acid levels.
- the combinations in this document may cause rhabdomyolysis.
- PA / a / 2005/013654 illustrates the combination of orlistat and bupropion. This combination has the disadvantage that the Bupropion use can cause seizures and adverse effects at the patient's nervous system level.
- the combination has cardioprotective effect.
- the present invention is directed to a combination and to a pharmaceutical composition comprising effective amounts of orlistat, or its pharmaceutically acceptable salts, and resveratrol, or its pharmaceutically acceptable salts.
- the present invention also relates to the combination of orlistat, or its pharmaceutically acceptable salts, and resveratrol, or its pharmaceutically acceptable salts, for the preparation of a medicament for the treatment of overweight, obesity and related health problems.
- the invention relates to the process for preparing a pharmaceutical composition comprising orlistat and resveratrol.
- Figure 1 is a graph showing the state of obesity induced by a hypercaloric diet in Winstar rats after 3 weeks.
- Figure 2 corresponds to a graph on weight gain in the experimental groups.
- Results of the groups standard diet (GCN), hypercaloric diet (GCP), hypercaloric diet with administration of orlistat (GHO), hypercaloric diet with administration of resveratrol (GHR), hypercaloric diet and administration of the combination of orlistat-resveratrol in two different concentrations (GH Combination 1 and GH Combination 2).
- Figure 3 is a graph of daily food consumption during the study period. Animals treated with standard diet maintain a constant pattern of food consumption (between 13 and 15 g) and animals fed with the hypercaloric diet showed a plateau in consumption lower than 16 g / day.
- Figures 4A to 4C are graphs of blood pressure monitoring during the study period.
- Figure 4A shows the result of diastolic pressure
- Figure 4B shows the course of systolic pressure
- Figure 4C shows the average pressure. This reading is of all the rats of the experimental groups throughout the 3 weeks. Those animals fed with a hypercaloric diet showed an increase in pressure figures of up to 25 mmHg, which means hypertension, a condition that was reversed in week 3 after treatment with the combination of orlistat-resveratrol.
- Figure 5 is a graph of serum glucose monitoring. It can be seen that during the 3-week period, all groups except those treated with the higher dose orlistat-resveratrol combination significantly increased postprandial glucose levels.
- Figure 6 corresponds to a follow-up graph of serum liver transaminase. The result shows that the hypercaloric diet does not alter the activity of any of the transaminases.
- a combination comprising orlistat and resveratrol is provided.
- the inventors of the present invention have discovered that the joint administration of these two drugs has a synergistic effect in the treatment of overweight, obesity and related health problems, such as metabolic syndrome, cardiovascular problems, etc.
- the inventors of the present invention found that the combination of orlistat with resveratrol has a pharmacological effect in rats with experimental obesity, finding a synergistic effect in weight reduction. During the study, the results show that the combination of orlistat and resveratrol is effective in reducing weight compared to the separate administration of these active agents.
- Hypercaloric diet + orlistat-resveratrol 1.0 mg / 5.0 mg / Kg 3 times a day.
- the doses used of orlistat and resveratrol were based on extrapolation of the clinical use of the drugs, individually, in humans, that is, the dose of orlistat (1.7 mg / kg) is equivalent to the dose of 120 mg consumed in clinical
- the 10 mg / kg dose was used for weight control and resveratrol.
- the foregoing does not limit the use of other doses ranging from 30 mg to 360 mg orlistat and 100 mg to 2000 mg resveratrol, preferably 1000 mg.
- the experimental animals were subdivided into groups of two animals and placed in cages that allowed them free access to food and drinking water. Each day at the same time (morning, afternoon and evening), the registration of the consumption of both, as well as the replacement of the initial preset amount (150 g of food and 250 mL of water). On pre-established days, blood pressure measurement was also performed by non-invasive methods.
- the main variable to measure the effectiveness of the treatment was the weight reduction at 3 weeks, although the time course of weight gain during that period was assessed, as well as the ability of each treatment to reduce excessive weight gain ( "obesity").
- Rats in all groups were evaluated for possible spontaneous adverse effects such as: reduction of reflexes, walking well, corneal reflex before and after drug treatments. Additionally, serum oxaloacetic and pyruvic transaminase levels were determined at the end of the study to assess possible liver abnormalities.
- Winstar rats who received a diet high in fat and carbohydrates were used to resemble the pathological states of the Zjucker Rat, such as being overweight at an early age (3 to 5 weeks), hyperlipidemia, hypercholesterolemia and hyperinsulinemia, and hypertrophy development and adipocyte hyperplasia.
- Winstar rats were given a diet high in fat and carbohydrates for 3 weeks and considered that the rat is in a state of obesity when the difference between the negative and positive control is 30% (See figure 1).
- cardiovascular status blood pressure, lipid levels and cholesterol
- cardiovascular status blood pressure, lipid levels and cholesterol
- Figures 4A to 4C show the temporal courses of systolic, diastolic and mean blood pressure of the rats of all experimental groups over 3 weeks of follow-up.
- those animals fed with a hypercaloric diet showed an increase in pressure figures of up to 25 mmHg at two weeks, that is, it could be proposed that animals under this condition go through a "hypertension" stage, however such status reverses as of the 3rd week, apparently the weight loss that is given by the administration of the treatments influences.
- the greatest decrease in blood pressure occurs for the orlistat-resveratrol combination, however, an increased effect is observed for the treatment of orlistat-resveratrol 1.7 / 10 mg / kg of weight in the decrease in pressure.
- Figure 6 shows an increase in transaminase levels when using treatments compared to the hypercaloric diet.
- the increase was smaller and no damage was observed in the animals, so an increase in the safety of the use of the orlistat-resveratrol combination was observed.
- orlistat and resveratrol, or their pharmaceutically acceptable salts is administered in different formulations, a preferred formulation is oral for its convenience of administration. This can be presented as a suspension, tablet, tablet, granulate, powder, capsule, etc.
- the present invention offers a stable pharmaceutical composition which surprisingly manages to solve formulation problems due to the physical and chemical characteristics of orlistat and resveratrol. It should not be forgotten that orlistat melts at temperatures of approximately 43 ° C (40 ° -44 °), a temperature that is reached during the manufacturing processes, which makes it difficult to obtain a stable formulation that meets the requirements for use in humans and acceptable in appearance.
- thermo-resistant system Due to the different physicochemical properties of orlistat (waxy characteristic) and resveratrol (dust characteristic), it was observed that it is impossible to keep the active ingredients in a single dosing unit, however, in the present invention there is a thermo-resistant system in which allows the coexistence of active ingredients.
- the process of the present invention comprises mixing orlistat with pharmaceutically acceptable excipients among which are, without limitation, cellulose derivatives, microcrystalline cellulose, lactose or corn starch; heat the mixture at a temperature of 50 to 70 ° C; extrude the mixture and form the spheres comprising orlistat; cool the powders, and finally coat the powder mixture with a dispersion of resveratrol and a polymer selected from hydroxypropylmethylene cellulose, polyvinylpyrrolidone, hydroxypropyl cellulose or cellulose derivatives.
- This last step of coating the powders can be carried out in a fluidized bed equipment or the like.
- the combination of the invention can be used to prepare a medicament for the treatment of overweight, obesity and related health problems.
- the amount of orlistat used may be from 30 mg to 360 mg, preferably 120 mg.
- the amount of resveratrol used may vary from 100 mg to 2000 mg, preferably 1000 mg.
- Orlistat and resveratrol may be present in the same pharmaceutical form or may be present in different pharmaceutical forms or different pharmaceutical units.
- the invention has been described sufficiently that a person with average knowledge in the field can reproduce and obtain the results mentioned in this document. However, any person skilled in the art to which the present invention belongs may be able to make modifications not described in the present application. Therefore, if the subject matter claimed in the following claims is required for the application of these modifications in a given composition, said compositions should be within the scope of the present invention.
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- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR112013015489-6A BR112013015489A2 (pt) | 2010-12-21 | 2011-12-16 | combinação e composição para o tratamento de obesidade |
GB1312583.6A GB2500357B (en) | 2010-12-21 | 2011-12-16 | Combination and composition for treating obesity |
ES201390069A ES2422877B1 (es) | 2010-12-21 | 2011-12-16 | Combinación y composición para el tratamiento de obesidad |
US13/996,410 US9433602B2 (en) | 2010-12-21 | 2011-12-16 | Combination and composition for treating obesity |
RU2013127794A RU2608928C2 (ru) | 2010-12-21 | 2011-12-16 | Фармацевтическая комбинация и композиция для лечения ожирения и ее применение |
CA2822213A CA2822213C (en) | 2010-12-21 | 2011-12-16 | Combination and composition for treating obesity |
CR20130298A CR20130298A (es) | 2010-12-21 | 2013-06-19 | Combinación y composición para el tratamiento de la obesidad |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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MXMX/A/2010/014484 | 2010-12-21 | ||
MX2010014484A MX336980B (es) | 2010-12-21 | 2010-12-21 | Combinacion y composicion para el tratamiento de obesidad. |
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WO2012085785A1 true WO2012085785A1 (es) | 2012-06-28 |
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PCT/IB2011/055723 WO2012085785A1 (es) | 2010-12-21 | 2011-12-16 | Combinación y composición para el tratamiento de obesidad |
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US (1) | US9433602B2 (es) |
AR (1) | AR084435A1 (es) |
BR (1) | BR112013015489A2 (es) |
CA (1) | CA2822213C (es) |
CL (1) | CL2013001731A1 (es) |
CO (1) | CO6751242A2 (es) |
CR (1) | CR20130298A (es) |
DO (1) | DOP2013000144A (es) |
ES (1) | ES2422877B1 (es) |
GB (1) | GB2500357B (es) |
GT (1) | GT201300169A (es) |
MX (1) | MX336980B (es) |
PE (1) | PE20140697A1 (es) |
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WO (1) | WO2012085785A1 (es) |
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US10743813B2 (en) | 2014-09-11 | 2020-08-18 | Rattan Nath | Diabetes control using postprandial feedback |
WO2016168388A2 (en) | 2015-04-14 | 2016-10-20 | Palatin Technologies, Inc. | Therapies for obesity, diabetes and related indications |
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WO2001000205A1 (en) * | 1999-06-24 | 2001-01-04 | Knoll Aktiengesellschaft | Pharmaceutical composition containing sibutramine and orlistat |
WO2004080450A2 (en) * | 2003-03-13 | 2004-09-23 | Fournier Laboratories Ireland Limited | Combined use of a fibrate and orlistat for the treatment of obesity |
US20060111435A1 (en) * | 2003-12-29 | 2006-05-25 | President And Fellows Of Harvard College | Compositions for treating or preventing obesity and insulin resistance disorders |
WO2007008548A2 (en) * | 2005-07-07 | 2007-01-18 | Sirtris Pharmaceuticals, Inc. | Methods and related compositions for treating or preventing obesity, insulin resistance disorders, and mitochondrial-associated disorders |
WO2010045522A2 (en) * | 2008-10-16 | 2010-04-22 | Metabolous Pharmaceuticals, Inc. | Combination therapies for the treatment of obesity |
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DE19539361A1 (de) * | 1995-10-23 | 1997-04-24 | Basf Ag | Verfahren zur Herstellung von mehrschichtigen, festen Arzneiformen zur oralen oder rektalen Verabreichung |
US20060153889A1 (en) * | 2005-01-10 | 2006-07-13 | Friel Francis M | Discontinuous surface coating for particles |
US7771632B2 (en) * | 2006-05-15 | 2010-08-10 | American Leistritz Extruder Corp. | Continuous melt spheronization apparatus and process for the production of pharmaceutical pellets |
EA201070378A1 (ru) * | 2007-09-17 | 2010-08-30 | Др. Редди`С Лабораторис Лтд. | Фармацевтические составы орлистата |
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2010
- 2010-12-21 MX MX2010014484A patent/MX336980B/es active IP Right Grant
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2011
- 2011-12-16 WO PCT/IB2011/055723 patent/WO2012085785A1/es active Application Filing
- 2011-12-16 PE PE2013001445A patent/PE20140697A1/es active IP Right Grant
- 2011-12-16 BR BR112013015489-6A patent/BR112013015489A2/pt not_active Application Discontinuation
- 2011-12-16 US US13/996,410 patent/US9433602B2/en active Active
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- 2011-12-16 CA CA2822213A patent/CA2822213C/en active Active
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WO2004080450A2 (en) * | 2003-03-13 | 2004-09-23 | Fournier Laboratories Ireland Limited | Combined use of a fibrate and orlistat for the treatment of obesity |
US20060111435A1 (en) * | 2003-12-29 | 2006-05-25 | President And Fellows Of Harvard College | Compositions for treating or preventing obesity and insulin resistance disorders |
WO2007008548A2 (en) * | 2005-07-07 | 2007-01-18 | Sirtris Pharmaceuticals, Inc. | Methods and related compositions for treating or preventing obesity, insulin resistance disorders, and mitochondrial-associated disorders |
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Also Published As
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CO6751242A2 (es) | 2013-09-16 |
ES2422877R1 (es) | 2013-09-26 |
US20130316005A1 (en) | 2013-11-28 |
CL2013001731A1 (es) | 2014-01-10 |
ES2422877B1 (es) | 2014-07-17 |
GB2500357B (en) | 2017-09-06 |
ES2422877A2 (es) | 2013-09-16 |
US9433602B2 (en) | 2016-09-06 |
CA2822213C (en) | 2018-06-19 |
PE20140697A1 (es) | 2014-06-25 |
BR112013015489A2 (pt) | 2018-05-15 |
AR084435A1 (es) | 2013-05-15 |
GB201312583D0 (en) | 2013-08-28 |
CA2822213A1 (en) | 2012-06-28 |
RU2608928C2 (ru) | 2017-01-26 |
MX2010014484A (es) | 2012-06-21 |
CR20130298A (es) | 2013-07-09 |
DOP2013000144A (es) | 2013-10-15 |
GT201300169A (es) | 2014-04-04 |
GB2500357A (en) | 2013-09-18 |
MX336980B (es) | 2016-02-09 |
RU2013127794A (ru) | 2015-01-27 |
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