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US20040033983A1 - Anti-obesity compositions - Google Patents

Anti-obesity compositions Download PDF

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Publication number
US20040033983A1
US20040033983A1 US10/421,111 US42111103A US2004033983A1 US 20040033983 A1 US20040033983 A1 US 20040033983A1 US 42111103 A US42111103 A US 42111103A US 2004033983 A1 US2004033983 A1 US 2004033983A1
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Prior art keywords
composition
glucomannan
orlistat
lipase inhibitor
weight
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US10/421,111
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English (en)
Inventor
Jacques Bailly
Rainer Martin
Susanne Raab
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Hoffmann La Roche Inc
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Individual
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Assigned to HOFFMANN-LA ROCHE INC. reassignment HOFFMANN-LA ROCHE INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: F. HOFFMANN-LA ROCHE AG
Assigned to F. HOFFMANN-LA ROCHE AG A SWISS COMPANY reassignment F. HOFFMANN-LA ROCHE AG A SWISS COMPANY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BAILLY, JACQUES, MARTIN, RAINER EUGEN, RAAB, SUSANNE
Publication of US20040033983A1 publication Critical patent/US20040033983A1/en
Priority to US11/348,828 priority Critical patent/US7816342B2/en
Abandoned legal-status Critical Current

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    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • 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
    • A61K31/70—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
    • A61K31/736—Glucomannans or galactomannans, e.g. locust bean gum, guar gum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents

Definitions

  • the field of this invention is the field of combating obesity utilizing compositions containing lipase inhibitors.
  • Such strategies are i) use of a surfactant to stabilize the oil/water interface in order to prevent coalescence of the oil emulsion in the colon, ii) enhancing water viscosity in the colon to reduce both intensity and frequency of droplet-droplet interactions and by that reducing the probability of coalescence, iii) physical absorption of oil by a lipophilic compound, or iv) increasing the natural stool mass by facilitating bacterial growth in the colon.
  • the present invention relates to pharmaceutical compositions and methods for preventing and treating obesity. More particularly, the invention relates to a composition comprising a lipase inhibitor, preferably a compound of formula I (orlistat),
  • the invention also relates to the compositions as described above for use in the treatment and prevention of obesity and to a process for preparing a composition as described above, comprising mixing a lipase inhibitor with glucomannan and optionally one or more pharmaceutically acceptable excipients.
  • the invention also refers to a kit for treatment of obesity, said kit comprising a) a first component which is a lipase inhibitor and b) a second component which is glucomannan as defined above, e.g. in an oral unit dosage form, preferably comprising a) from 1 to 100 doses units of orlistat and b) from 1 to 100 doses units of a glucomannan.
  • kits for treatment of obesity comprising a) a first component which is a lipase inhibitor and b) a second component which is glucomannan in oral unit dosage forms.
  • the present invention also relates to the use of a composition as defined above in the manufacture of medicaments useful for the treatment and prevention of obesity and to the use of a lipase inhibitor as defined above in the manufacture of a medicament for the treatment and prevention of obesity in a patient who is also receiving treatment with glucomannan as defined above.
  • This use of glucomannan and lipase inhibitor refers to the simultaneous, separate or sequential use for the treatment and prevention of obesity.
  • the invention is directed to a method of treatment of obesity in a human in need of such treatment which comprises administration to the human of a therapeutically effective amount of a lipase inhibitor and a therapeutically effective amount of glucomannan as defined above.
  • the method refers to the simultaneous, separate or sequential administration of the compounds.
  • a further embodiment of the present invention is a lipase inhibitor and glucomannan or konjac as defined above as a combined preparation for simultaneous, separate or sequential use for the treatment and prevention of obesity.
  • the invention also refers to the use of glucomannan or konjac as defined above in the manufacture of medicaments useful for the treatment and prevention of gastrointestinal side effects selected from the group of oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence and to a method of treatment or prevention of gastrointestinal side effects selected from the group of oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence in a human in need of such treatment which comprises administration to the human of a therapeutically effective amount of konjac or glucomannan as defined above.
  • the invention is directed to a lipase inhibitor and glucomannan or konjac as defined above for simultaneous, separate or sequential use for the treatment and prevention of obesity.
  • FIG. 3 The free oil reducing effect of different types of glucomannan in % relative to controls (data as means ⁇ SE).
  • the administration of glucomannan in conjunction with lipase inhibitors for combating obesity reduces the gastro-intestinal side effects produced by the lipase inhibitor such as oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence in humans.
  • compositions which contain the lipase inhibitors, preferably orlistat, and glucomannan. These compositions may contain pharmaceutically acceptable excipients.
  • the pharmaceutical composition contains from about 0.1% by weight to about 10% by weight, based upon the weight of the composition, of the lipase inhibitor and from about 10% by weight to about 75% by weight, based upon the weight of the composition, of glucomannan and from about 0.1% to 90% by weight, based upon the weight of the composition of one or more pharmaceutically acceptable excipients.
  • the composition of this invention be formulated in a unit oral dosage form.
  • a method for combating obesity in human patients by administering to said human patients the lipase inhibitor, preferably orlistat, in an effective amount to treat said obesity, in conjunction with glucomannan.
  • both the glucomannan and lipase inhibitor can be orally administered in conventional oral dosage forms such as through the compositions of this invention.
  • the glucomannan and lipase inhibitor can be administered simultaneously, separately or sequentially for carrying out the method of this invention.
  • the two components i.e. the lipase inhibitor and the glucomannan be administered within two hours of each other.
  • the glucomannan which is administered in conjunction with lipase inhibitor is administered in an amount of about 0.5 g to 10 g per day after administration of lipase inhibitor.
  • the lipase inhibitor is generally administered from 2 to preferably 3 times per day.
  • any effective amount of lipase inhibitors for combating obesity can be administered to human patients.
  • the use of these lipase inhibitors and their dosages are well known for combating obesity.
  • combating obesity it is meant that the composition of this invention can be utilized either for prevention and/or treatment of obesity.
  • the compositions of this invention can contain any effective amount of the lipase inhibitor needed for administration to combat obesity.
  • kits can be provided containing the lipase inhibitor, preferably orlistat as one component, and the glucomannan as the second component.
  • each of the components contains the glucomannan and lipase inhibitor, such as orlistat, in the compositions in oral unit dosage forms.
  • the first or lipase inhibitor component of the kit can contain from 1 to 100 oral dosage units of the lipase inhibitor, such as orlistat, and the second or glucomannan component contains from about 1 to 100 oral dosage units of glucomannan.
  • Lipase inhibitor is present in each oral unit dosage form in an amount of from 5 to 120 mg and the glucomannan is provided in a separate oral unit dosage form which constitutes the second component.
  • the glucomannan can be provided in the separate oral unit dosage form in an amount of from about 0.5 g to about 10 g.
  • the orilstat be administered in an amount of from 16 mg to 720 mg in each unit oral dosage form contained within the first component of the kit.
  • glucomannan can be administered such as glucomannan itself or in the form of konjac, e.g. konjac flour, in any amount sufficient to reduce the gastrointestinal adverse events (GI-AE) commonly observed after administration of a lipase inhibitor such as orlistat or artificial fat substitutes. Therefore the method of this invention involves the use of glucomannan in an amount sufficient to reduce the gastrointestinal adverse effects observed after administration of a lipase inhibitor. These effects include oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence in humans.
  • GI-AE gastrointestinal adverse events
  • Konjac Amorphophallus konjac
  • This flour comprises a highly viscous sol of glucomannan and soluble starches when reconstituted in water.
  • the principal soluble constituent is glucomannan (formula II), a polysaccharide comprised of D-glucose and D-mannose, which is useful as an ingredient in various foodstuffs, as well as in industrial applications such as films, oil drilling fluids and paints.
  • the present invention refers to a composition comprising a lipase inhibitor and glucomannan. Unless otherwise indicated the following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein.
  • lipase inhibitor refers to compounds which are capable of inhibiting the action of lipases, for example gastric and pancreatic lipases.
  • orlistat and lipstatin as described in U.S. Pat. No. 4,598,089 are potent inhibitors of lipases.
  • Lipstatin is a natural product of microbial origin, and orlistat is the result of a hydrogenation of lipstatin.
  • Other lipase inhibitors include a class of compound commonly referred to as panclicins. Panclicins are analogues of orlistat (Mutoh et al, J. Antibiot., 47(12):1369-1375 (1994)).
  • lipase inhibitor refers also to polymer bound lipase inhibitors for example described in International Patent Application WO 99/34786 (Geltex Pharmaceuticals Inc.). These polymers are characterized in that they have been substituted with one or more groups that inhibit lipases.
  • lipase inhibitor also comprises pharmaceutically acceptable salts of these compounds.
  • lipase inhibitor also refers to 2-oxy-4H-3,1-benzoxazin-4-ones which have been described in International Patent Application WO 00/40569 (Alizyme Therapeutics Ltd.), e.g.
  • Orlistat is a known compound useful for the control or prevention of obesity and hyperlipidemia. See, U.S. Pat. No. 4,598,089, issued Jul. 1, 1986, which also discloses processes for making orlistat and U.S. Pat. No. 6,004,996, which discloses appropriate pharmaceutical compositions. Further suitable pharmaceutical compositions are described for example in International Patent Applications WO 00/09122 and WO 00/09123. Additional processes for the preparation of orlistat are disclosed in European Patent Applications Publication Nos. 185,359, 189,577, 443,449, and 524,495.
  • Orlistat is preferably orally administered from 60 to 720 mg per day in divided doses two to three times per day. Preferred is wherein from 180 to 360 mg, most preferably 360 mg per day of a lipase inhibitor is administered to a human subject, preferably in divided doses two or, particularly, three times per day.
  • the subject is preferably an obese or overweight human, i.e. a human with a body mass index of 25 or greater.
  • the lipase inhibitor be administered within about one or two hours of ingestion of a meal containing fat.
  • Orlistat can be administered to humans in conventional oral compositions, such as tablets, coated tablets, hard and soft gelatin capsules, emulsions or suspensions.
  • carriers which can be used for tablets, coated tablets, dragées and hard gelatin capsules are lactose, other sugars and sugar alcohols like sorbitol, mannitol, maltodextrin, or other fillers; surfactants like sodium lauryl sulfate, Brij 96, or Tween 80; disintegrants like sodium starch glycolate, maize starch or derivatives thereof; polymers like povidone and crospovidone; talc; stearic acid or its salts and the like.
  • Suitable carriers for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like.
  • the pharmaceutical preparations can contain preserving agents, solubilizers, stabilizing agents, wetting agents, emulsifying agents, sweetening agents, coloring agents, flavoring agents, salts for varying the osmotic pressure, buffers, coating agents and antioxidants. They can also contain still other therapeutically valuable substances.
  • the formulations may conveniently be presented in unit dosage form and may be prepared by any methods known in the pharmaceutical art. Preferably, orlistat is administered according to the formulation shown in the Examples and in U.S. Pat. No. 6,004,996, respectively.
  • the term “konjac flour” refers to a hydrocolloidal polysaccharide obtained from the tubers of species of Amorphophallus konjac .
  • the perennial tuber is unique to Asia and especially cultivated in Japan.
  • Konjac flour is a high molecular weight, nonionic glucomannan consisting primarily of mannose and glucose molecules combined in a mole ratio of 1.6:1.0. It is a slightly branched polysaccharide connected by beta 1-4 linkages and has an average molecular weight ranging from 200,000 to 2,000,000 daltons. Acetyl groups along the glucomannan backbone contribute to its solubility and are located, on average, at every 9 to 19 sugar unit.
  • Refined konjac flour is easily soluble in cold water and forms a highly viscous solution with a pH between 4.0 and 7.0. Addition of a mild alkaline solution results in the formation of a heat-stable gel that resists melting, even under extended heating conditions.
  • the purification process for konjac flour is carried out in large-scale extraction plants. The konjac tubers are first pulverized, and then the collected glucomannan particles are polished in order to dislodge and extract noxious materials adhering to them. This process yields a refined konjac flour with high degree of purity that improves product solubility, stability and overall functionality. The particles are tasteless, odorless and white in color.
  • Konjac flour and glucomannan are commercially available products (Kyoei Konnyaku, Inc., Behr, Wunderlich & Co., Provisco, FMC Biopolymers, Naturland, SiberHegner and Co. Ltd.). The preparation and use have been described e.g. in U.S. Pat. Nos. 3,767,424, 3,973,007, 4,588,589, 5,486,364, 5,486,364, 5,733,593, 5,536,521, 6,126,906, etc.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising a lipase inhibitor and glucomannan.
  • this composition may contain one or more pharmaceutically acceptable excipients.
  • the glucomannan may be provided in form of konjac.
  • the konjac contains at least 80% by weight glucomannan, more preferably at least 90% by weight glucomannan.
  • the glucomannan or konjac may be provided in form of konjac powder, e.g. konjac flour.
  • the lipase inhibitor is orlistat. These 80% by weight are based on the total weight of the composition.
  • compositions incorporating both a compound of a lipase inhibitor and glucomannan are important embodiments of the present invention.
  • Such pharmaceutical compositions comprise a therapeutically effective amount of each of the compounds for the given purpose.
  • Each dosage unit can obtain the daily doses of both compounds or may contain a fraction of the daily dose, such as one-third of the doses.
  • each dosage unit may contain the entire dose of one of the compounds, and a fraction of the dose of the other compound. In such case the patient would daily take one of the combination dosage units, and one or more units containing only the other compound.
  • the composition comprises a) 0.1 to 20% (w/w) lipase inhibitor, b) 10 to 75% (w/w) glucomannan such as konjac, and c) 0.1 to 90% (w/w) of one or more pharmaceutically acceptable excipients. More preferably, a composition may comprise a) 0.1 to 10% (w/w) lipase inhibitor, b) 20 to 75% (w/w) glucomannan and c) 0.1 to 90% (w/w) of one or more pharmaceutically acceptable excipients. Preferably, the amount of one or more pharmaceutically acceptable excipients is from about 5 to 50% (w/w), more preferably 5 to 20%.
  • the composition may contain a) from about 5 to about 1000 mg lipase inhibitor, e.g. orlistat, in an amount of e.g. from about 10 to about 500 mg lipase inhibitor, preferably from about 20 to about 100 mg lipase inhibitor, e.g. from about 10 to about 360 mg orlistat, more preferably from about 30 to about 120 mg orlistat, more preferably from about 40 to about 80 mg orlistat and b) from about 0.5 to about 10 g glucomannan, preferably from about 0.5 to about 8 g glucomannan, and more preferably from about 0.5 to about 6 g glucomannan.
  • the weight percent is based upon the total weight of the composition
  • the pharmaceutically acceptable excipients may be selected from the group consisting of fillers, surfactants, disintegrants, binders, lubricants, flowability enhancers, sweeteners, and colorants, e.g. a composition may comprise of a) about 5 to about 1000 mg lipase inhibitor; b) about 0.5 to about 10 g glucomannan; and optionally pharmaceutically acceptable excipients selected from the group of about 0.1 to about 10 g fillers, about 0.05 to about 5.0 g surfactants, about 0.05 to about 2.0 g disintegrants, about 0.02 to about 5.0 g binder, about 0.001 to about 1.0 g lubricants, about 0.1 to about 5.0 g flowability enhancers, about 0.01 to about 4.0 g sweeteners, and about 0.001 to about 0.5 g colorants.
  • a composition may comprise of a) about 5 to about 1000 mg lipase inhibitor; b) about 0.5 to about 10 g glucomannan;
  • the pharmaceutically acceptable excipients may be selected from the group consisting of fillers, e.g. sugars and/or sugar alcohols, e.g. lactose, sorbitol, mannitol, maltodextrin, etc.; surfactants, e.g. sodium lauryl sulfate, TPGS, Brij 96 or Tween 80; disintegrants, e.g. sodium starch glycolate, maize starch or derivatives thereof; binder, e.g. povidone, crosspovidone, polyvinylalcohols, hydroxypropylmethylcellulose; lubricants, e.g. stearic acid or its salts; flowability enhancers, e.g. silicium dioxide; sweeteners, e.g. aspartame; and/or colorants, e.g. ⁇ -carotene.
  • fillers e.g. sugars and/or sugar alcohols, e.g. lactose
  • the composition comprises a) about 0.1 to about 20% (w/w) lipase inhibitor; b) 10 to about 75% (w/w) glucomannan such as konjac; and optionally pharmaceutically acceptable excipients selected from the group of about 0.1 to about 20% (w/w) fillers, about 0.1 to about 10% (w/w) surfactants, about 0.1 to about 10% (w/w) disintegrants, about 0.1 to about 10% (w/w) binder, about 0.1 to about 10% (w/w) lubricants, about 0.1 to about 10% (w/w) flowability enhancers, about 0.1 to about 10% (w/w) sweeteners, and about 0.1 to about 5% (w/w) colorants.
  • excipients selected from the group of about 0.1 to about 20% (w/w) fillers, about 0.1 to about 10% (w/w) surfactants, about 0.1 to about 10% (w/w) disintegrants, about 0.1 to about 10% (w/w) binder, about
  • the composition may contain a) from about 5 to about 1000 mg lipase inhibitor, e.g. orlistat, in an amount of e.g. from about 10 to about 500 mg lipase inhibitor, preferably from about 20 to about 100 mg lipase inhibitor, e.g. from about 10 to about 360 mg orlistat, more preferably from about 30 to about 120 mg orlistat, more preferably from about 40 to about 80 mg orlistat and b) from about 0.5 to about 10 g glucomannan, preferably from about 0.5 to about 8 g glucomannan, and more preferably from about 0.5 to about 6 g glucomannan.
  • lipase inhibitor e.g. orlistat
  • Oral dosage forms are the preferred compositions for use in the present invention and these are the known pharmaceutical forms for such administration, for example tablets, capsules, bars, sachets, granules, syrups and aqueous or oily suspensions.
  • the pharmaceutically acceptable excipients are known in the pharmacist's art. Tablets may be formed from a mixture of the active compounds with fillers, for example calcium phosphate; disintegrating agents, for example maize starch, lubricating agents, for example magnesium stearate; binders, for example microcrystalline cellulose or polyvinylpyrrolidone and other optional ingredients known in the art to permit tabletting the mixture by known methods.
  • capsules for example hard or soft gelatin capsules, containing the active compound with or without added excipients, may be prepared by known methods.
  • the contents of the capsule may be formulated using known methods so as to give sustained release of the active compound.
  • the tablets and capsules may conveniently each contain the amounts of lipase inhibitor and glucomannan as described above.
  • dosage forms for oral administration include, for example, aqueous suspensions containing the active compounds in an aqueous medium in the presence of a non-toxic suspending agent such as sodium carboxymethylcellulose, and oily suspensions containing the active compounds in a suitable vegetable oil, for example arachis oil, olive oil or myritol 318.
  • the active compounds may be formulated into granules with or without additional excipients.
  • the granules may be ingested directly by the patient or they may be added to a suitable liquid carrier (e.g. water) before ingestion.
  • the granules may contain disintegrants, e.g. an effervescent pair formed from an acid and a carbonate or bicarbonate salt to facilitate dispersion in the liquid medium.
  • the active compounds may, if desired, be associated with other compatible pharmacologically active ingredients.
  • vitamin supplements may be administered with the compounds in accordance with the present invention.
  • Both compounds, the lipase inhibitor and glucomannan may be administered simultaneously, separately or sequentially (e.g. orlistat as described above and glucomannan in the evening).
  • the compounds or compositions are administered during a meal or 1-2 hours before or after a meal.
  • the amount of glucomannan to be administered will depend on a number of factors including the age of the patient, the severity of the condition and the past medical history of the patient and lies within the discretion of the administering physician.
  • glucomannan is active in reducing gastro-intestinal adverse events (GI-AE) commonly observed after administration of a lipase inhibitor such as orlistat.
  • GI-AE gastro-intestinal adverse events
  • Emulsion Stability Konjac t/min c (% w/w) 1 10 40 70 100 130 160 220 300 0.01 l* l l l l l l l 0.1 l l l l l l l l 0.5 l l l l l l l l l 1.0 m m l l l l l l 1.5 h m m m m m m m m m m m m m m m m 2.0 h m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m
  • Glucomannan was tested as konjac powder.
  • the konjac powder is obtained from the root of a tree ( Amorphophallus konjac ) and this the natural source of glucomannan. This substance was tested in the acute side effect model at the dosage of 4 g/meal.
  • Volunteers treated with glucomannan/orlistat had no fat excretion decrease (compared to volunteers treated with orlistat alone, data not shown) suggesting no interaction of glucomannan with orlistat. No major AEs associated with the glucomannan treatment has been reported.
  • Composition Quantity g/Chewable Ingredient tablet glucomannan 1.5 g sorbitol 1.1 g lactose anhydrous 0.376 g talc 0.16 g sodium stearyl fumarate 0.064 g Total 3.2 g
  • Composition Ingredient Quantity g/Sachet glucomannan 4 g aspartame 0.5 g beta-carotene 0.001 g Total 4.501 g
  • Composition Quantity g/Chewable Ingredient tablet glucomannan 0.5 g lactose 0.5 g microcrystalline cellulose 1.31 g sodium lauryl sulfate 0.09 g sodium starch glycolate 0.3 g polivinylpyrrolidone 0.15 g talc 0.15 g Total 3.0 g
  • Composition Quantity g/Chewable Ingredient tablet orlistat 0.06 g glucomannan 0.75 g lactose 0.5 g microcrystalline cellulose 1.31 g sodium lauryl sulfate 0.09 g sodium starch glycolate 0.3 g polivinylpyrrolidone 0.15 g talc 0.15 g Total 3.31 g
  • Composition Ingredient Quantity g/Sachet orlistat 0.12 g glucomannan 4 g saccharose 2.8 g beta-carotene 0.001 g silicium dioxide 0.5 g Total 7.421 g
  • Composition Quantity g/Chewable Ingredient tablet orlistat 0.12 g glucomannan 2.0 g sodium starch glycolate 0.1 g microcrystalline cellulose 0.2 g sodium lauryl sulfate 0.03 g crospovidone 0.1 g aspartame 0.15 g talc 0.15 g magnesium stearate 0.03 g Total 2.85 g

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  • Diabetes (AREA)
  • Child & Adolescent Psychology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
US10/421,111 2002-04-26 2003-04-23 Anti-obesity compositions Abandoned US20040033983A1 (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1679009A1 (de) * 2005-01-05 2006-07-12 ABOCA S.p.A. Pharmazeutische und diätetische Zusammensetzungen bestehend aus pflanzlichen Ballaststoffen
US20100221326A1 (en) * 2007-09-12 2010-09-02 Mader S.R.L. Pharmaceutical compositions for oral use for treating patients affected by obesity
US20120077872A1 (en) * 2009-04-03 2012-03-29 Ems S.A. Preservative-free pharmaceutical tetrahydrolipstatin compositions
US20180280405A1 (en) * 2004-08-25 2018-10-04 Essentialis, Inc. Pharmaceutical formulations of potassium atp channel openers and uses thereof

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101252635B1 (ko) * 2006-04-20 2013-04-10 (주)아모레퍼시픽 리파아제 저해제 및 친유성 오일흡수제를 포함하는 약학조성물 및 이로부터 제조된 경구 투여용 제제
GB0618725D0 (en) * 2006-09-23 2006-11-01 Jagotec Ag Composition containing inhibitors of gastro-intestinal lipase
FR2918567B1 (fr) * 2007-07-11 2012-08-03 Pf Medicament Composition pharmaceutique stable d'un sel hydrosoluble de vinorelbine.
US20120053172A1 (en) 2009-02-12 2012-03-01 Cooperatieve Mirzorg U.A. Use of a combination of diazoxide and metformin for treating obesity or obesity related disorders
US9034342B2 (en) * 2010-03-25 2015-05-19 Gateway Health Alliances, Inc Methods and compositions to reduce fat gain, promote weight loss in animals
WO2012070702A1 (ko) * 2010-11-25 2012-05-31 주식회사 삼양사 올리스태트 및 키토산 함유 조성물 및 그 제조방법
US10507194B2 (en) 2015-08-10 2019-12-17 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Methods for treating obesity
CN108524495B (zh) * 2018-07-10 2019-02-26 中山万汉制药有限公司 奥利司他在制备治疗便秘的药物中的用途
NL2022615B1 (en) 2019-02-21 2020-08-31 Patrick Alexander Unger Pharmaceutical composition comprising tetrahydrocannabivarin for the prevention and treatment of overweight
CN115671132B (zh) * 2020-06-01 2024-03-15 山东新时代药业有限公司 一种益生菌和益生元的组合物及其应用
WO2023038575A2 (en) * 2021-09-09 2023-03-16 Junion Labs Pte. Ltd. Superabsorbent hydrogels with lipase inhibitor

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5477953A (en) * 1992-03-16 1995-12-26 Environmental Products Corporation Filter and filter cleaning system for a reverse vending machine
US5486364A (en) * 1992-12-30 1996-01-23 Fmc Corporation Readily available konjac glucomannan as a sustained release excipient
US5942500A (en) * 1998-04-27 1999-08-24 Perry; Stephen C. Dietary composition to reduce dietary fats
US6030953A (en) * 1998-08-14 2000-02-29 Hoffmann-La Roche Inc. Pharmaceutical composition containing chitosan
US6358522B1 (en) * 1998-08-14 2002-03-19 Hoffmann-La Roche Inc. Pharmaceutical compositions containing lipase inhibitor
US6534087B2 (en) * 2000-06-27 2003-03-18 Hoffmann-La Roche Inc. Process for preparing a pharmaceutical composition

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4582714A (en) * 1982-07-08 1986-04-15 Mars G.B. Limited Air or oil emulsion food product having glucomannas as sole stabilizer-thickener
CA1247547A (en) * 1983-06-22 1988-12-28 Paul Hadvary Leucine derivatives
CA2098167C (en) 1992-06-24 2006-12-19 Dorothea Isler Foodstuffs and feedstuffs containing a lipase inhibitor
WO1998033395A1 (fr) * 1997-02-03 1998-08-06 Takahisa Shiota Aliment prepare a partir d'un sol de farine de konjak
US6004996A (en) * 1997-02-05 1999-12-21 Hoffman-La Roche Inc. Tetrahydrolipstatin containing compositions
US6093439A (en) * 1998-05-08 2000-07-25 National Starch And Chemical Investment Holding Corporation Hydrocolloid composition for use as a gelling agent viscosifier and stabilizer
JP4265911B2 (ja) 2000-07-28 2009-05-20 エフ．ホフマン−ラ ロシュ アーゲー 新規医薬組成物
US6558690B2 (en) * 2000-12-15 2003-05-06 Pacific Health Laboratories, Inc. Nutritional composition for improving the efficacy of a lipase inhibitor
JP2004111852A (ja) * 2002-09-20 2004-04-08 Fujitsu Ltd 半導体装置及びその製造方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5477953A (en) * 1992-03-16 1995-12-26 Environmental Products Corporation Filter and filter cleaning system for a reverse vending machine
US5486364A (en) * 1992-12-30 1996-01-23 Fmc Corporation Readily available konjac glucomannan as a sustained release excipient
US5942500A (en) * 1998-04-27 1999-08-24 Perry; Stephen C. Dietary composition to reduce dietary fats
US6030953A (en) * 1998-08-14 2000-02-29 Hoffmann-La Roche Inc. Pharmaceutical composition containing chitosan
US6358522B1 (en) * 1998-08-14 2002-03-19 Hoffmann-La Roche Inc. Pharmaceutical compositions containing lipase inhibitor
US6534087B2 (en) * 2000-06-27 2003-03-18 Hoffmann-La Roche Inc. Process for preparing a pharmaceutical composition

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180280405A1 (en) * 2004-08-25 2018-10-04 Essentialis, Inc. Pharmaceutical formulations of potassium atp channel openers and uses thereof
EP1679009A1 (de) * 2005-01-05 2006-07-12 ABOCA S.p.A. Pharmazeutische und diätetische Zusammensetzungen bestehend aus pflanzlichen Ballaststoffen
US20100221326A1 (en) * 2007-09-12 2010-09-02 Mader S.R.L. Pharmaceutical compositions for oral use for treating patients affected by obesity
US20120077872A1 (en) * 2009-04-03 2012-03-29 Ems S.A. Preservative-free pharmaceutical tetrahydrolipstatin compositions

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EP1501498B1 (de) 2009-12-30
DE60330764D1 (de) 2010-02-11
RU2297221C2 (ru) 2007-04-20
PL373692A1 (en) 2005-09-05
ATE453390T1 (de) 2010-01-15
US7816342B2 (en) 2010-10-19
JP2005531536A (ja) 2005-10-20
CN1649580A (zh) 2005-08-03
BRPI0309406B1 (pt) 2017-04-11
JP4234017B2 (ja) 2009-03-04
BR0309406A (pt) 2005-02-01
PA8571901A1 (es) 2004-05-26
TW200404536A (en) 2004-04-01
RU2004134573A (ru) 2005-10-10
AR039664A1 (es) 2005-03-02
KR20040104626A (ko) 2004-12-10
CA2483002A1 (en) 2003-11-06
US20060135471A1 (en) 2006-06-22
WO2003090742A1 (en) 2003-11-06
EP1501498A1 (de) 2005-02-02
AU2003222814B2 (en) 2006-08-24
CN1325050C (zh) 2007-07-11
PE20040596A1 (es) 2004-09-15
KR100625399B1 (ko) 2006-09-20
ES2335876T3 (es) 2010-04-06
GT200300094A (es) 2004-01-15
PL216022B1 (pl) 2014-02-28
MXPA04010371A (es) 2005-02-03
CA2483002C (en) 2011-02-01

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