WO2014032676A1 - Préparation orale solide destinée au traitement et/ou à la prévention du surpoids et/ou permettant de stabiliser le niveau de glycémie chez un patient - Google Patents
Préparation orale solide destinée au traitement et/ou à la prévention du surpoids et/ou permettant de stabiliser le niveau de glycémie chez un patient Download PDFInfo
- Publication number
- WO2014032676A1 WO2014032676A1 PCT/DK2013/050278 DK2013050278W WO2014032676A1 WO 2014032676 A1 WO2014032676 A1 WO 2014032676A1 DK 2013050278 W DK2013050278 W DK 2013050278W WO 2014032676 A1 WO2014032676 A1 WO 2014032676A1
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- WIPO (PCT)
- Prior art keywords
- alginate
- oral formulation
- solid oral
- gel
- formulation according
- Prior art date
Links
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- 238000009472 formulation Methods 0.000 title claims abstract description 118
- 239000007787 solid Substances 0.000 title claims abstract description 87
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- 239000008280 blood Substances 0.000 title claims abstract description 22
- 210000004369 blood Anatomy 0.000 title claims abstract description 22
- 235000000346 sugar Nutrition 0.000 title claims abstract description 16
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- 230000000087 stabilizing effect Effects 0.000 title claims abstract description 8
- 235000010443 alginic acid Nutrition 0.000 claims abstract description 186
- 229920000615 alginic acid Polymers 0.000 claims abstract description 186
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims abstract description 159
- 229940072056 alginate Drugs 0.000 claims abstract description 148
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- 239000001814 pectin Substances 0.000 claims description 37
- 229920001277 pectin Polymers 0.000 claims description 37
- 235000010987 pectin Nutrition 0.000 claims description 37
- 210000002784 stomach Anatomy 0.000 claims description 35
- 239000003795 chemical substances by application Substances 0.000 claims description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 21
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 12
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- 238000000034 method Methods 0.000 claims description 10
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- 230000008961 swelling Effects 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 238000004132 cross linking Methods 0.000 claims description 7
- 235000010216 calcium carbonate Nutrition 0.000 claims description 6
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
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- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 4
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- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 4
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
-
- 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
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Definitions
- a solid oral formulation for treatment and/or prevention of overweight and/or for stabilizing blood sugar levels in an individual relates to a solid oral formulation comprising an alginate for the treatment and/or prevention of overweight for both therapeutic and non-therapeutic purposes.
- the present invention also relates to the use of said formulation for stabilizing blood sugar levels in an individual.
- the main object is to reduce the caloric intake on a daily basis, however in order for an individual to be able to follow a diet, it is important that the individual does not feel hunger nor the complications normally associated with hunger, e.g. faintness.
- foods containing strong- gelling fibers may provide a safe and efficacious strategy for reducing food and thereby caloric intake by stimulating endogenous satiety signaling and/or by stabilizing blood sugar levels.
- alginate is a non-digestible polysaccharide and can as such be classified as dietary fibre.
- Dietary fibre has a range of positive physiological benefits and studies have shown that dietary alginate exhibits many of these. There is an improvement in GI barrier function and a reduction in the damaging potential of the luminal contents with changes in the colonic microflora. Dietary alginate reduces intestinal nutrient absorption and promotes satiety both of which have implications for the control of Type II diabetes and obesity. (Brownlee et al., 2005 I. A. Brownlee, A. Allen, J. P. Pearson, P.W. Dettmar, M.E. Havler and M.R. Atherton et al., Alginate as a source of dietary fiber, Critical Reviews in Food Science and Nutrition 45 (6) (2005), pp. 497-510. View Record in Scopus / Cited By in Scopus (28) .
- Dietary fibres are grouped into 2 types: soluble and insoluble fibres.
- the insoluble dietary fibres are present in coarse bread and starchy vegetables.
- examples of insoluble fibres comprise cellulose, hemicellulose, lignin and pectin.
- the soluble fibres are present in fruit and vegetables.
- Examples of soluble fibres comprise guar, dextran, alginate, starch, amylose, pectin, amylopectin, xanthan, pullulan, carrageenan and gellan. Attempts to use soluble fibres in the production of drinkable products for the control of food intake are disclosed in various patent applications.
- WO2008/098579 discloses a diet product comprising an alginate in an aqueous dissolved or swelled form at a pH not causing the alginate to gel.
- the type of alginate is of a low molecular weight having a molecular weight of 150.000 or less.
- the pH of the diet product is decreased to around 2, the viscosity may be increased 50 times or more, resulting in a high viscosity gel.
- WO 2008/022857 discloses a shelf-stable liquid composition comprising a mixture of alginate, HM pectin and water. According to the description, upon ingestion, the liquid composition enhances, the feeling of satiety and/or induces satiation upon ingestion.
- such beverages may be effective for the treatment of overweight or obesity.
- the vast amount of water included in the known beverages may increase the price of the product due to higher transportation and storage costs.
- consumers, following a diet including the prior art liquid compositions, need regularly to carry heavy bags from the shop to their homes.
- a solid oral formulation is suggested as an alternative. Furthermore, it is believed that consumer compliance is increased because patients not only are used to being treated with capsules, tablets or other solid oral formulations when ill or following a dietary plan, but also because consumption of a solid formulation is much easier to incorporate into a full working day or take before a meal at a restaurant, instead of having to consume larger quantities of a meal substitute.
- WO 2003/086360 relates to an oral solid formulation for the production of satiety and for weight loss.
- the product consists of a dried, porous gel or foam of e.g. an aluminum alginate, i.e. a previously produced gel or foam has been dried, and it is said gel, which is being re-hydrated in the stomach.
- the above-mentioned patent application does not include clinical tests, but it is asserted that the product, when orally ingested results in a prolonged gastric emptying time and an increased feeling of satiety.
- the solid formulation in WO 03/086360 is not capable of dissolving at the pH-value in the stomach and said gel will therefore only work as a sponge.
- a solid oral formulation with similar properties is known from WO 2004/056343.
- the present inventors have however discovered that a simple swelling of the oral formulation provides an inadequate feeling of satiety, and that addition of certain ingredients is necessary to obtain a better formulation comprising an alginate, when a solid oral formulation is wanted for the treatment of obesity or overweight, and/or for reducing oscillation of the blood sugar levels, including the metabolic syndrome .
- the inventors have surprisingly found that in order to obtain a large gel strength as well as a sufficient volume, it is important that the formulation comprises a disintegration agent, ensuring that the solid form breaks up when it comes into contact with aqueous fluid, in order to obtain acceptable dissolution rates of the alginates in the formulation.
- Availability of the alginate in the solid formulation depends on the formulations ability to disintegrate fast enough in the relevant dissolution media. If said disintergration is not present an undesirable effect is found not only on the rate of gel formation but also the degree of alginates turning into a gel, accordingly affecting both the gel strength and stability.
- Disintegrating agents are thus added to the solid formulation for according to the invention to promote the disintegration of the formulation into smaller fragments in an acidic aqueous environment and, thereby increase the available surface area and thus promote a more rapid exposure of the alginate to the content of the stomach.
- the disintegrating agents can be categorized in three different mechanisms of action: wicking, swelling and deformation. Effective disintegrating agents that do not swell are believed to impart their disintegrating action through porosity and capillary action, also called wicking.
- Tablet porosity provides pathways for the penetration of fluid into the tablets. Disintegrating particles with low cohesiveness and compressibility act to enhance porosity and provide these pathways into the tablet. Liquid is drawn up or "wicked" into these pathways through capillary action and rupture the inter- particulate bonds causing the tablet to break apart.
- Materials suitable for acting as wicking agents may be, but are not limited to, colloidal silicon dioxide, kaolin, titanium dioxide, fumed silicon dioxide, alumina, niacinamide, sodium lauryl sulfate, low molecular weight polyvinyl pyrrolidone, m- pyrol, bentonite, magnesium aluminum silicate, polyester, polyethylene, and microcrystalline cellulose.
- Swelling is believed to be a mechanism in which certain disintegrating agents such as starch impart their disintegrating effect.
- certain disintegrating agents such as starch impart their disintegrating effect.
- swelling agents may be pregelatinized starch or any type of modified starch, and sodium carboxy methylcellulose.
- Deformation is generally thought to be an “elastic” phenomenon where particles deformed under pressure will return to their original shape when the pressure is removed. However, with the compression forces involved in tableting, these particles are believed to be deformed more permanently and are said to be “energy rich” with this energy being released upon exposure to an aqueous liquid.
- the disintegrating agent is an alkaline salt.
- alkaline salt such as sodium bicarbonate
- the amount of disintegrating alkaline salt, such as sodium bicarbonate is present in an amount of 5% by weight or less, based on the weight of the alginate.
- the disintegrating agent is a combination of one or more of the wicking agents, swelling agents and alkaline salts .
- the objectives behind adding a disintegrating agent are to increase surface area of the tablet fragments and to overcome cohesive forces that keep particles together in a tablet.
- the solid formulation according to the invention will not only lead to increased viscosity of stomach contents inducing a feeling of satiety but will also increase the time period the gel remains in the stomach.
- a solid oral formulation comprising an alginate for the treatment of or prevention of overweight or obesity
- having an alginate amount which is sufficient for the formation of a gel having a gel strength of 1000 Pa or more, when dissolved or swelled in an aqueous liquid at simulated gastric conditions at a pH of 3 or less.
- the obtained solid formulation will disintegrate in the stomach where the content of the formulation will be converted into a thick gel whereby the consumer will experience a feeling of satiety. Furthermore, it is likely that the gel formed has an active function in detaining fats, thereby inhibiting their uptake in the stomach or bowels. By these means some food constituents, incl . fats, can pass undigested. Passage through the stomach and bowels is thereby regulated by the formulation as a prolonged time of passage of consumed foods is observed after intake of the solid formulation.
- Any alginate in any amount may be used in the present invention provided it forms a gel at a pH of 3 or less, said gel having a gel strength of 1000 Pa or more. It is however preferred that a gel strength is higher e.g. 2000 Pa, 4000 Pa, 8000 Pa or more as the gel formed in the stomach otherwise can be degraded to fast to ensure a prolonged feeling of satiety.
- alginate gels can either be obtained due to the presence of multivalent cations in the formulation e.g. in the form of calcium (ionic gelation) or alternatively be obtained when the pH is less than 3.5 (acid gelation) . It is however preferred to use an alginate which undergoes ionic gelation as the inventors has found that it will be possible to use lower concentrations/amounts of alginates in the solid formulation according to the invention.
- alginates of any molecular weight may be used for the preparation of the solid oral formulation.
- the molecular weight of the alginate in order to obtain a fast dissemination or dissolution of the solid oral formulation without the use of disintegrating agents, the molecular weight of the alginate should not be above 150,000 Da. However, in order to provide a sufficient effect on satiety, the molecular weight of the alginate should be at least 10, 000 Da. In other embodiments of the present invention it is preferred to use a molecular weight of the alginate, which is 200,000 Da, or above, such as 350,000 Da or above.
- the formulation also comprises a suspending agent it is possible to obtain a very good solubility using alginates having a high molecular weight, i.e. weights above 150 kDa.
- the tern "suspending agent” means any agent capable of providing the desired solubility and/or dispersion of the alginate in the formulation. Without being bound by theory it is believed that the suspending agent ensures that the alginate particles are diluted and separated by keeping the alginate particles apart, as they are wetted.
- the ratio of the alginate to the suspending agent is preferably about 1:1 to 20:1, more preferably 5:1 to 10:1, as the inventors have shown said ratios to provides the highest solubility .
- a preferred suspending agent is selected from the group consisting of inulin, polydextrose , dextrin, oligofructose, and combinations thereof.
- Alginates are polysaccharides that provide the main structural component of brown algae (seaweeds) .
- Alginates are linear copolymers of (1 4) linked ⁇ -d-mannuronic acid (M) and GC-1- guluronic acid (G) .
- M linked ⁇ -d-mannuronic acid
- G GC-1- guluronic acid
- the distribution of M and G in alginate chains gives rise to three different block types, namely blocks of poly-M, blocks of poly-G and alternating MG blocks.
- the chemical composition of alginate is variable according to the seaweed species, within different parts of the same plant (stem or leaf), seasonal changes and the conditions of the sea.
- the guluronic segments can associate with the calcium ions to form aggregates similar to an "egg-box" .
- the alginate chains are in a regular pleated structure, which is stabilized by multivalent cations, each neutralizing a negative charge on two different chains. As a result, alginates richer in these blocks form stronger gels.
- the affinity for cations and the gel forming properties of the alginate are mostly related to the content of G residues as when two G residues are adjacent in the polymer they form a binding site for polyvalent cations.
- the alginate has a ratio of mannuronic acid to guluronic acid (M/G) of less than 1, suitably as low as 0.8 or less.
- the amount of guluronic acid is above 60% and the amount of mannuronic acid is below 40% of the total content. Since only guluronic acid is regarded as being responsive to calcium gelation it is preferred to use an alginate having a high guluronic acid content.
- the alginate used in the present invention is provided in a form in which less than 80%, such as less than 60%, preferable less than 40% and most preferred less than 20% of the total amount of guluronate and mannuronate units are estrified with an alcohol group such as an methyl, ethyl, propyl, hydroxypropyl , hydroxypropylmethyl , propylene glycol group. Particularly, it is preferred that the alginate does not contain any esterified mannuronate or gulluronate groups .
- alginates of this type can be mentioned Satialgine XPU-LVG500 (Algogel DPG JO) obtainable from Cargill (Minneapolis, MN, USA), however a preferred alginate is Manugel® DMB obtainable from FMC Biopolymer as said alginate form a strong gel in the stomach. Further specific alginates to be considered is Manugel® DMB, Protanal® SF 120 RB and Protanal® GP 5450.
- the alginate is a sodium alginate, however, other metal salts of alginate can also be used. Examples are potassium alginate, which is widely used in foods as a stabilizer, thickener, and emulsifier.
- Further metal alginates include calcium alginate, magnesium alginate and ammonium alginate.
- the alginate in the solid composition is a combination of alginates, preferably a composition comprises at least one low viscosity alginate having a viscosity of less than about 100 mPaS in a 1 wt% aqueous solution and at least one high viscosity alginate having a viscosity of more than about 100 mPaS in a 1 wt% aqueous solution.
- low or high viscosity alginates means those alginates having a viscosity lower or higher, respectively, than about 100 mPaS in a 1 wt% aqueous solution when determined on a Brookfield viscometer model LV using spindle No 2 at 60 rpm at 20°C.
- low or high viscosity alginates and preferred alginate combinations comprising high and low alginates are disclosed in the applicants international application no. WO2012/163366 Al .
- one preferred combination of alginates is about 1.45 g Manugel® GMB; about 1.45 g Manugel® GHB, about 1,5 g Protanal® GP1740, about 0.25 g Protanal® LF 5/60, and about 0.5 g Protanal® GP5450.
- a different combination of alginates which is also disclosed in WO2012/163366 Al is about 0,48 g Manugel® GMB; about 1 g Protanal® GP1740, and about 0,1 g Protanal® GP5450. Said combinations have proven to be especially beneficial for being dissolved in liquid, which is also beneficial when the solid formula is to be dissolved in the stomach. It will be evident for a person skilled in the art, that different amounts of the preferred combinations of alginates can be used, preferably the above mutual ratios.
- any kind of multivalent cation source can be used in the present invention, however a preferred source of multivalent cations is a calcium salt.
- Said salt is preferably selected from the group consisting of calcium phosphate, calcium carbonate, calcium sulfate, calcium oxide, calcium lactact, calcium citrate, and calcium chloride.
- the used calcium salt has a solubility of at least 5 mg per ml at 20°C and pH 7, ensuring that the calcium ions are available shortly after the solid formulation has been disintegrated in the stomach.
- All known alginate preparations in the art rely on endogenous gastric acid to trigger the solubility of the calcium salt, however since gastric pH is not a consistent factor and varies among individuals, e.g. due to meal consumption, time and medication usage, and compositions which are decomposition-sensitive to pH can be affected accordingly. It is therefore advantageously if the calcium ions are immediate available after the formulation reaches the stomach, and using a calcium salt having a good solubility ensures that the calcium ions does not become the limited factor during geletion.
- cross-linking polyvalent metal ions are generally provided in an amount of 10% by weight or less, based upon the amount of alginate.
- a salt comprising calcium ion may be included to increase the gel strength of the gel formed of the alginate.
- salts including an aluminium ion are aluminium carbonate, aluminium chloride, and aluminium hydroxide.
- the amount of salt comprising the cross-linking polyvalent metal ions is typically, 15% by weight, preferably 25% by weight of the alginate in a unit dosage form.
- solid oral formulation according to the invention does not comprise any additional active pharmaceutical ingredients.
- the present inventors have found that satiety- inducing factors are strongly correlated with the volume of a solid product containing soluble dietary fibers and the gel strength thereof.
- the effect of a solid product according to the invention administered with a volume of 330 mL was not significant, when compared to the administration of 330 mL of placebo, whereas when the solid formulation was administered with an increased volume the feeling of satiety was increased significantly which subsequently lead to a reduction in prospective food intake.
- the gel at simulated gastric conditions of pH 3 has a volume between 400 ml and 600 ml, preferably about 500 ml as said volume has proven to be especially relevant in order to obtain the desired satiety effects .
- the solid formulation according to the present invention is taken in combination with a sufficient amount of aqueous liquid, preferably in an amount of 350ml or more.
- the aqueous liquid is ingested together with the oral solid formulation or preferably with 30 minutes after the administering of the solid oral formulation.
- the amount of aqueous liquid may be increased so that the volume may be 400 mL, 450 mL, 500 mL, 550 mL, 600 mL, or more.
- the present invention relates to a solid oral formulation mentioned above and the use thereof for increasing the perceived satiety.
- it relates to the solid oral formulation mentioned above and the use thereof for decreasing the prospective food intake.
- the gel weight obtained after the pH value is lowered from pH 7 to pH 2 is above 90 g/100 ml water, more preferably above 93 g/100 ml water and even more preferably above 95 g/100 ml water, as an increase in gel weight is beneficial also this has proven not only to be beneficial in relation to a feeling of satiety but will also slow gastric emptying, stimulate gastric stretch receptors and reduce intestinal nutrient uptake and influence the glycaemic response .
- the inventors have surprisingly found that by raising the concentration of multivalent cations available during gelation it is possible to lower the concentration of the alginates in the solid formulation and still obtain the same or equivalent gel strength, volume and weights as obtained using higher alginate concentrations.
- the solid oral formulation of the present invention may be administered as a single unit dosage or multiple dosages, i.e. 2, 3, 4 or more unit dosages.
- a single unit dosage or multiple dosages i.e. 2, 3, 4 or more unit dosages.
- three daily dosages is contemplated.
- Each unit dosage may comprise a concentration of the alginate adjusted to meet the result desired.
- each dosage may comprise at least 200 mg alginate, preferably at least 500 mg or at least 800 mg, preferably at least 1200 mg.
- Each dosage may comprise up to 5 g alginate, preferably around 3 g.
- the subject receiving the product in question in terms of unit dosage (s) is generally an adult. If an adolescent or a child is treated the number of unit dosages may be adjusted to the age of the person being treated.
- the solid oral formulation prepared using the alginates mentioned above may be described in terms of the viscosity and/or the tensile modulus of their respective physical state after having been exposed to conditions simulating the gastric conditions, such as aqueous conditions at a pH of 2 or less.
- the viscosity may readily be measured using any conventional equipment, for example using a rheometer of the Bohlin product range of Malvern Instruments Ltd. (Malvern, Worcestershire, UK) such as a Bohlin CVOR rheometer.
- the gel strength can be measured as Young's (tensile) Modulus following the formula:
- E is the Young's modulus (modulus of elasticity)
- F is the force applied to the gel
- a 0 is the original cross-sectional area through which the force is applied; AL is the amount by which the length of the gel changes;
- L 0 is the original length of the object.
- the alginate used in the present invention When the alginate used in the present invention is exposed to a pH of 3 or less, e.g. as found in gastric juice (around 1.5 at fasting conditions), it forms a gel. The formation of the gel may be observed with a corresponding increase in viscosity. Thus, when exposed to acidic conditions at a pH of 3 or less, the solid oral formulation containing the alginate will swell or dissolve and obtain a certain viscosity. The gel formed upon lowering the pH will generally be of non-Newtonian rheology. For example, the gel may be characterised as being of pseudo- plastic rheology meaning that the observed viscosity of the gel is decreased when the gel is exposed to an increasing shear rate.
- the viscosity of the gel will typically be recorded at ambient temperature at shear rates between 0.1 s 1 and 90 s 1 , e.g. the viscosity of the gel may be measured at 20 s 1 and the recorded viscosity may be compared to the viscosity of the aqueous liquid before formation of the gel.
- the solid oral formulation as described in the present invention when dissolved or swelled in an aqueous liquid to be consumed together with the oral formulation, when measured at a shear rate of 0.1 s 1 , pH 3, has a viscosity of 7 pas or more.
- the solid oral formulation may also be described in terms of its water retention capacity upon the formation of a gel.
- the formation of a gel will result in binding of water molecules within the gel, and in one embodiment the obtained gel has a water retention capacity (WRC) of at least 13 g of water per gram of the formulation. It is believed that this WRC may be indicative of the satiety inducing effect of the gel, i.e. of the formulation. In particular, the higher the WRC is of an alginate the better the satiety effect is of the formulation.
- the WRC of the formulation may be determined by the formation of a gel by lowering the pH and determining the mass of the gel and the mass of the free water, and from these parameters enable a calculation on how much water has been retained in the gel.
- the WRC may be measured by centrifugation of the gel and recording the weight of the gel and the weight of the supernatant; appropriate conditions may be centrifugation for 10 min at 3500 rpm (e.g. in a Rotina 48R centrifuge from Hettich Zentrifuge) .
- the gel formation caused by the alginate in the oral formulation may also be reversible, when no or only a small amount of cross-linking metal ions, such as calcium ions, are used.
- the formation of the gel by lowering the pH to 3 or less may be reversed by increasing the pH to above 3, suitably above pH 5.
- the present inventors believe that a reversible formation of a gel is advantageous for certain products which increase satiety.
- the solid oral formulation of the present invention may contain further biopolymers.
- biopolymers include pectin, cellulose, xanthan, curdlan, pullulan, hyaluronic acid, gelatin, chitin, inulin, carrageenan, xanthan gym, dextran, etc.
- the alginate is used in combination with pectin.
- Pectins are a common type of carbohydrate gelling agents, generally obtained from dilute acid extracts of citrus or apple pulp. They are an important constituent of the cell walls and soft tissue of vegetables and fruits, where they contribute to the mechanical properties of the cell wall and influence cell adhesion.
- pectins are found in root crops such as carrots and beetroot, as well as in tubers, such as potatoes; and are commercially extracted from citrus peels, apple pomace and sugar beet pulp.
- Pectin is composed of long, regular sequences of 1, 4-linked-D-galacturonate residues which in nature may be partially methyl-esterified .
- a typical pectin molecule comprises of 200 to 1000 galacturonic acid units connected in a linear chain having alternating rhamnose units inserted into the main uronide chain. The ester content varies with the source of the raw material and may also be varied during extraction.
- HM pectins high methoxylated pectins (hereafter referred to as HM pectin) , which are characterized by a degree of methoxylation above 50%, more particularly between 50% and 80%, and low methoxylated pectin (hereafter referred to as LM pectin) having a degree of methoxylation below 50%, more particularly between 30% and 50%.
- degree of methoxylation is intended to mean the extent to which free carboxylic acid groups contained in the polygalacturonic acid chain are present as the methyl ester. Both HM and LM pectins form gels.
- LM pectin forms a gel in the presence of calcium; thus, it is "calcium-reactive.”
- the calcium-LM pectin gel network is built by formation of what is commonly referred to as an "egg-box" junction zone in which Ca 2+ causes the cross-linking of two stretches of polygalacturonic acid chains.
- Calcium-LM pectin gel formation is influenced by several factors, including DM, ionic strength, pH, and molecular weight.
- HM pectin forms a gel in the presence of high concentrations of co-solutes, such as sucrose, at low pH .
- HM pectins are generally not reactive with calcium ions and therefore cannot form a calcium gel.
- certain HM pectins have been reported to be calcium sensitive and capable of calcium gel formation.
- HM pectins can be made calcium-reactive by a block wise de-esterification process while still having a DM of >50%. See, Christensen et al . U.S. Pat. no. 6, 083, 540.
- Pectins are typically utilized in the food industry and classified by the FDA as "GRAS" (Generally Regarded As Safe) . Also, they have been used as colloidal and anti-diarrhea agents.
- pectins have been utilized in the areas of medical device and drug delivery (Thakur et al . , Critical Reviews in Food Science & Nutrition 37, 47-73, 1997) . In the case of drug delivery, pectin has found its presence in many experimental formulations for oral drug delivery to the colon because bacteria present in this region of the intestines readily degrade pectin.
- the solid formulatin according to the present invention comprises 0.05-5.0 wt% HM pectins, which are preferably characterized by a degree of methoxylation of above 50%, preferably within the range of 50- 90%, still more preferably within the range of 55-85% most preferably within the range of 60-80%.
- the molecular weight of the pectin does not affect the gel strength of the gel formed upon ingestion, but does affect the viscosity of the liquid composition itself. More in particular, it was found that low molecular weight HM pectins form similarly strong interactions with alginate, as do high molecular weight HM pectins. Thus, the addition of low molecular weight HM pectin will reduce the viscosity of the product and improve the mouth feel thereof, without a concomitant decrease in strength of the gel particles formed in the stomach as compared with the use of high molecular weight HM pectins.
- solid formulations wherein the average molecular weight of the HM pectin is within the range of 50-500 kDa, more preferably within the range of 75-250 kDa, still more preferably 90-200 kDa.
- HM pectins are used in combination with alginates, since they are capable of forming a sufficiently rigid matrix at the pH found in the stomach of a normal human, typically a pH of 3 or less.
- the solid oral formulation according to the invention typically contains 0.08 - 2.5 wt . %, preferably 0.1 - 1.0 wt . %, more preferably 0.2 - 0.8 wt . % of HM pectin based on the total weight of the composition.
- the oral formulation prepared by using an alginate is not particularly limited to the amount of the alginate, as long as the gel formed has gel strength of 1000 Pa or more at simulated gastric conditions of pH 3 or less.
- a skilled person may easily determine the amount of alginate to be used in a solid oral formulation by using the formula for Young's modulus above.
- the amount of an aqueous liquid and the composition of the oral formulation, including the type of alginate a simple routine experiment will show whether a gel with a strength of 1000 Pa or more is formed.
- the amount of alginate in the solid formulation is selected in the range of 0.5 g to 20 g.
- the solid oral formulation may be present as a single or several unit dosages to make it possible to swallow the formulation.
- the oral formulation according to the present invention may comprise one or more pharmaceutical acceptable carriers in addition to the active constituent ( s ) described above.
- the carrier (s) must be "acceptable” in the sense of being compatible with the other ingredients of the composition and not deleterious to the recipients thereof.
- the alginate is purified.
- the amount of the formulation required for treatment or prevention will vary according to the form of administration, the disorder to be treated, the condition, age, the file history of the subject, and the gelenic formulation of the formulation, etc.
- the amount of active components are preferably present in an amount effective to alleviate the symptoms of the patient.
- the solid oral formulation of the present invention may be formulated as tablets, pills, capsules, powders, etc.
- the solid oral formulation may furthermore contain one or more carriers.
- carrier refers to a diluent, adjuvant, excipient, or vehicle with which the active components are administered.
- the carriers in the formulation may comprise a binder, such as microcrystalline cellulose, polyvinylpyrrolidone (polyvidone or povidone), gum tragacanth, gelatine, starch, lactose or lactose monohydrate ; a lubricant or surfactant, such as magnesium stearate, or sodium lauryl sulphate; a glidant, such as colloidal silicon dioxide; a sweetening agent, such as sucrose or saccharin; and/or a flavouring agent, such as peppermint, methyl salicylate, or orange flavouring.
- a binder such as microcrystalline cellulose, polyvinylpyrrolidone (polyvidone or povidone), gum tragacanth, gelatine, starch, lactose or lactose monohydrate ; a lubricant or surfactant, such as
- the formulation for oral administration may be obtained by compression or moulding, optionally with one or more accessory ingredients.
- Compressed tablets may be prepared by mixing the constituent ( s ) , and compressing this mixture in a suitable apparatus into tablets having a suitable size.
- the alginate may be mixed with a binder, a lubricant, an inert diluent and/or a disintegrating agent and the alkaline salt may be mixed with a diluent, a lubricant and/or a surfactant.
- the alginate powder may be dry-mixed mixed with a binder, such as microcrystalline cellulose and/or a surfactant, such as sodium lauryl sulphate and/or a disintegrating agent and/or a salt comprising a cross- linking polyvalent metal ion until a homogeneous mixture is obtained.
- a binder such as microcrystalline cellulose and/or a surfactant, such as sodium lauryl sulphate and/or a disintegrating agent and/or a salt comprising a cross- linking polyvalent metal ion until a homogeneous mixture is obtained.
- another binder such as polyvidone
- This mixture may be passed through granulating sieves if needed and dried by desiccation before compression into tablets in a standard compressing apparatus.
- the tablets are prepared without the addition of carriers.
- the free-flowing alginate is compressed into tablets optional after mixing with magnesium stearate.
- Conventional methods for producing a solid form of the pharmaceutical composition may be found in the
- a tablet may be coated or uncoated.
- An uncoated tablet may be scored.
- a coated tablet may be coated with sugar, shellac, film or other enteric coating agents.
- the solid oral formulation is in the form of a shell/core capsule wherein the core comprises the formulation according to the invention, preferably in the form of a powder or a viscous paste, and the shell is arranged to quickly dissolve when the capsule reaches the stomach.
- the core comprises the formulation according to the invention, preferably in the form of a powder or a viscous paste
- the shell is arranged to quickly dissolve when the capsule reaches the stomach.
- Shell materials capable of easily dissolving in the stomach are known in the art, however gelatin is used in a preferred embodiment .
- the effect of the solid oral formulation of the present invention is believed to arise from an increased feeling of satiety (reduced appetite) in the subject to whom the solid oral formulation is administered, so that the subject after having been administered the product will tend to ingest less food (e.g. reduce the spontaneous energy intake) .
- the solid formulating according to the invention also provides less oscillation of the blood sugar and hence a stabile feeling of satiety and well being. It is known that stable blood sugar levels have a benefit in e.g. promoting weight loss; controlling hunger and reducing the risk of diabetes.
- the alginate when used for the preparation of the product according to the invention, is suited as a supplement which can reduce the amount of intake during ingestion of a meal and/or provide stabilized blood sugar levels.
- a preferred administration is prior to taking in a meal, e.g. as a "preload".
- the product is administered no more than 2 hours prior to a subject's intake of a meal.
- the administration of the product may also occur sooner than 2 hours prior to a meal intake, such as not more than 1 hour prior to a subject's intake of a meal, e.g. not more than 30 minutes prior to a subject's intake of a meal.
- Administration of the solid oral formulation may be relevant before any meal of the day for the subject, although it may be advantageous to administer the product prior to the meal of the day when the subject typically has the largest energy intake during the day.
- the product should be taken before any major meal intake, i.e. ideally three times per day before the three major meals (breakfast, lunch and dinner) .
- the effect of the solid oral formulation on satiety and blood sugar levels may also prevent the subject in consuming food or snacks between meals, which is considered advantageous for a weight loss plan for a subject.
- the solid oral formulation may be administered daily for a period with a duration of several days or weeks, for example as a course of a diet.
- the solid oral formulation is administered one or more times per day, the interval between administrations being at least 2 hours. Multiple administrations during a day may be especially advantageous in order for a subject to obtain a weight loss.
- the solid oral formulation is administered prior to all meals ingested by a subject during a day.
- the formaultion is administered before two meals, such as the two meals normally containing the highest energy intake for the subject during a day .
- the invention relates to a method for regulating, e.g. decreasing, appetite in a subject and/or for regulating the blood sugar levels in an individual.
- This method may e.g. be used in a diet with the intention to cause a weight loss to the subject; for example a subject may desire to loose weight for cosmetic reasons or alternatively the subject may be pathologically obese and be in need of weight loss for medical reasons.
- a diet dosage regimen will typically have a duration of several days or weeks depending on the aim of the subject undergoing the diet. For example, the subject may intend to loose a certain amount of body mass.
- the method for regulating appetite may thus comprise the daily intake, such as one to four times a day, preferably prior to a meal, of the formulation according to the invention in order to help the subject to follow the diet.
- the daily intake may be continued for the duration of the diet.
- Figure 1 shows the subjective feeling of appetite after intake of a sodium alginate supplement or a placebo based on the results of a Visual Analogue Scale (VAS) questionnaire.
- VAS Visual Analogue Scale
- Figure 2 shows the results presented in Figure 1 as incremental Area Under Curve (iAUC) .
- Figure 3 shows the results of the VAS questionnaire summed into an appetite score.
- Figure 4 shows the energy uptake during an ad libitum meal following intake of low and high dosages of alginate supplement and corresponding placebo supplements, respectively.
- Figure 5 shows self-reported estimates of well-being during a study of alginate test supplements or placebo.
- Figure 6 shows changes in systolic blood pressure during treatment with low dosage of alginate or placebo.
- Figure 7 shows changes in diastolic blood pressure during treatment with high dosage of alginate or placebo.
- Figure 8 shows the concentration of paracetamol in the blood after treatment with alginate supplement or placebo in low dosage .
- Figure 9 shows the concentration of paracetamol in the blood after treatment with alginate supplement or placebo in high dosage .
- Figure 10 shows the measurement of gel strength (elastic modul, Pas) recorded by oscillatory shear rheology of the Manugel® DMB.
- Figure 11 shows the gel strength (elastic modul, Pas) of Manugel® DMB in relation to the calcium content of the formulation according to the invention.
- Example 1 Characterization of alginates is described in Example 1 and 3, and in Example 2 a series of tests were designed to measure the effect of the solid oral formulation in combination with an intake of a volume liquid. 500 mL liquid was compared to an alginate preparation with 330 mL liquid.
- alginates Three different alginates were provided by Cargill, Inc. (Minneapolis, MN, USA) and characterised for potential use in a solid oral formulation.
- the alginates are referred to as Satialgine S20, XPU-LVE500 and XPU-LVG500.
- Solutions of the alginates of concentrations of 5, 7.5, 10, 12, 15, 20, 25, 30 and 35 g/L were prepared by initially weighing alginate powders on an analytical balance (Sartorius Analytic A2005, Sartorius, Germany) and then dissolving the alginates in 100 mL aliquots of water (milli-Q water) in glass beakers using magnetic stirring at 500 rpm. After 5 min the beakers were transferred to a water bath at 39°C and the fibers allowed to dissolve for a further 90 to 120 min.
- the fibre solution (at pH 5.50 to 6.00) or the gel mass (pH 1.20) was carefully transferred to a steel cup (DG 47/27 double gap, 10 ml or v25, 10 mL, respectively) and left standing for 5 min to equilibrate the sample before recording the viscosity at a constant temperature of 20°C.
- the measurements were conducted at different shear rates between 0.1 and 90 s 1 with 15 registrations over a time span of 5 min.
- Oscillatory shear rheology was analyzed on the rheometer at a constant shear frequency of 1 Hz; the stress amplitude was varied over 25 steps where the mechanical stress was controlled and gradually increased from 1 to 500 Pa. Stress was applied for 12 s at a time for each step and the amplitude was registered, and the elastic modulus (C) and the viscous modulus (G'') were calculated.
- the water retention capacities (WRC) of the gelled alginate samples were analyzed by centrifuging at 3500 rpm for 10 min in a Rotina 48R centrifuge from Hettich Zentrifuge, Germany and subsequently measuring the weight of the supernatant and the gel.
- the WRC was expressed in mass of water retained per liter of alginate solution prior to gelation and also in specific values per dry mass of alginate.
- the XPU-LVG500 alginate provided a viscosity at a shear rate of 20 s 1 of about 5 Pas at a concentration of 15 g/L, and at 25 g/L and above the viscosity was above 10 Pas.
- the XPU-LVE500 alginate did not provide a gel with a viscosity above 5 Pas at any tested concentration, whereas the Satialgine S20 did not provide a gel viscosity above 10 Pas at the tested concentrations .
- the Satialgine S20 alginate generally had higher values for the transition points than the other alginates.
- the XPU-LVG500 alginate provided a more resilient gel. Provision of a resilient gel upon acidification is seen as advantageous for the product.
- the XPU-LVG500 alginate was found to provide a higher WRC than the other alginates at all concentrations analysed. However, it was found that the specific WRC values varied with the concentration of alginate in the solution for all three alginates.
- Solutions of XPU-LVG500 consistently provided a WRC upon gel formation above 20 g/L at all concentrations, and a concentration of only 10 g/L of XPU-LVG500 was required to provide a WRC above 400 g per L alginate solution.
- the experiment was based on a total of four meal experiments.
- a meal experiment consisted of a standard breakfast meal of 2 MJ and an ad libitum lunch meal. Before each meal a test supplement was administered to the subjects with a pre-load time of half an hour.
- the test subjects were randomised into four different treatments by randomised block design. Each treatment being either a specific dosage of alginate or a placebo. Table 2 presents the type, concentration and dosage of the respective fibre under examination.
- the placebo and respective sodium alginate dosages (both in form of tablets) was tested with simultaneous consumption of either 330 mL water or 500 mL water, such that the final concentration of alginate in the stomach was 30g/l.
- the alginate containing tables contained NaHC0 3 as a disintegrating agent.
- the test subjects only performed limited physical activity which was reproduced with each experiment. In addition, the test subjects were restricted from hard exercise within 24 hours prior to each meal experiment. On the evening of the day prior to a meal experiment a standardised evening meal of 4 MJ from Department of Human Nutrition, University of Copenhagen was given. Intake of water, lavatory visits and other activity was noted on the first meal experiment and reproduced on later experiments .
- Table 2 presents the type, concentration and dosage of the respective fibre under examination.
- VAS Visual Analogue Scale
- each test subject reported their subjective feelings for each parameter to calculate the score; the score was expressed in the unit millimeters.
- test supplement was based on sodium alginate fibres (XPU- LVG500) extracted from brown seaweed in a concentration of 3% (equivalent to 15 g of fibre per 1 ⁇ 2 L of test supplement) . Characterisation of the alginate is described above in Example 1.
- test subjects experienced a significant increase in satiety and reduced prospective intake when treated with a high dosage of sodium alginate compared with placebo treatment.
- the corresponding treatment with low dosage of sodium alginate did not show a significant difference in appetite between alginate based supplement and the placebo treatment.
- Figure 2 plots the results of Figure 1 as incremental Area under Curve (iAUC); the iAUC is calculated as the area under the curve from 0 min to 270 min for each test supplement, i.e. placebo with 330 and 500 mL water and alginate with 330 and 500 mL water, respectively.
- Figure 2a shows the iAUC for the 330 mL water and alginate dosages
- Figure 2b shows the iAUC for 500 mL water and alginate dosages. Comparing the rating of appetite as iAUC it is also shown that treatment with high dosage of alginate-based tablets (15 gram) increases the feeling of satiety with approximately 40% (P ⁇ 0.01) and reduces prospective intake with approximately 50% (P ⁇ 0.01) .
- the results of the VAS questionnaire is summed into an appetite score calculated as described above for each of the four test supplements.
- the appetite scores are presented in Figure 3 as a function of time from 0 to 270 min;
- Figure 3a shows the appetite scores for the 330 mL water and alginate dosages, and
- Figure 3b shows the score for 500 mL water and alginate dosages.
- the experiments showed an increased appetite score of approximately 20% and 60% for low and high alginate-based supplement treatment, respectively, compared with the corresponding placebo treatments.
- An increased appetite score indicates increased satiety and feeling of fullness together with reduced hunger at prospective intake.
- Figure 5 presents the test subjects' self-reported estimates of well-being with Figure 5a showing the results for alginate unit dosages with 330 mL water and Figure 5b showing results for alginate unit dosages with 500 mL water. Neither side-effects nor measure of well-being indicate any significant difference between treatment with sodium alginate tablet or placebo tablets (P>0.1) .
- the diastolic blood pressure was significantly lowered during the course of the meal experiment when treating with a high dosage of alginate supplement.
- the low dosage did not show the same tendency.
- Treatment with high dosage of alginate supplement resulted in a significant reduction of the diastolic blood pressure of -2% compared with placebo results.
- Paracetamol was used as marker for the rate of emptying the stomach. Since paracetamol is not absorbed from the stomach but will only reach the blood stream after being absorbed from the duodenum the level of paracetamol in the blood provides an indication of the clearance rate of the stomach. Paracetamol was administered together with the breakfast meal in a total dosage of 1500 mg in 3 tablets of 500 mg each. The concentration of paracetamol in the blood was used as a measure for the rate of emptying the stomach.
- Figure 8 and 9 present the levels of paracetamol in the blood of the subjects for the 330 mL+alginate unit dosages and the 500 mL+alginate unit dosages, respectively.
- the values are displayed as a function of time from 0 to 270 min in the a- panels, and in the b-panels the integrated results of the a- panels are shown as iAUC-plots.
- the blood levels of paracetamol after administration of alginate dosage or placebo with 330 mL water did not differ significantly, and thus no effect was found on the rate of emptying the stomach.
- the alginate was prepared in four different concentrations (0.75 vol%, 1.5 vol%, 2.25 vol% and 3 vol%) and with addition of the insoluble salt of calcium carbonate 0.5 M as an active component for supporting the gel formation (at pH 1.5-2) .
- Table 5 shows the measurements conducted on Manugel DMB.
- the extracted fiber powder was weighed on an electronic weight (Sartorius Analytic A2005, Germany) to the nearest third decimal (mg) .
- Demineralized water (Milli-Q Plus) was measured in 100ml glass beaker. Mixing took place in 100ml disposable plastic cup on the magnetic stirring (KM02 Basic IKA-Werke) with 500 rpm for 5 min and then placed in water bath (37°c) allowing the fibers to fully hydrate of approximately 90-120 min. duration.
- Figure 10 shows the measurement of gel strength (elastic modul, Pas) recorded by oscillatory shear rheology and as evident from said figure the inventors observed a clear concentration- response curve as the gel strength increased with higher alginate concentrations. Elastic modulus increased with increased alginate concentration. By visually comparison the two highest concentration of Manugel DMB (2.25% and 3%) we observed a larger gel strength (-3500 Pa and -5100 Pa, respectively) .
- the experiments conducted using Manugel LBA and Protanal LFR 5/60 showed gel strengths around -2100 Pa for Manugel LBA (-2100 Pa) and around -2200 Pa for Protanal LFR 5/60.
- Manugel® DMB solution with 1.5% concentration increased the gel strength from - 1500 to -3000 Pa when calcium content was increased. This high gel strength was similar to the 2.25% concentration with 2.5ml and 5 ml calcium. This indicates that a lower Manugel® DMB concentration is possible for achieving acceptable gel strength as long as the calcium content is well monitored, making Manugel® DMB a desirable component in the solid oral formulation according to the invention.
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Abstract
L'invention concerne une préparation orale solide destinée au traitement et/ou à la prévention du surpoids et/ou permettant de stabiliser le niveau de glycémie chez un patient. La préparation selon l'invention contient un alginate destiné au traitement ou à la prévention du surpoids ou de l'obésité et/ou permettant de stabiliser le niveau de glycémie chez un patient, cette préparation étant administrée avec un liquide aqueux de 350 ml ou davantage, cette quantité d'alginate dans la préparation étant suffisante pour obtenir un gel présentant une résistance de 1000 Pa ou supérieure lorsqu'il est dissous ou gonflé dans le liquide aqueux dans des conditions de simulation gastrique de pH 3.
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CN113423386A (zh) * | 2019-10-01 | 2021-09-21 | 美国倍利年制药有限公司 | 治疗或预防肥胖和体重管理的方法 |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6083540A (en) | 1995-07-14 | 2000-07-04 | Danisco A/S | Process for stabilizing proteins in an acidic environment with a high-ester pectin |
WO2003086360A1 (fr) | 2002-04-15 | 2003-10-23 | Beisel Guenther | Agent destine a generer une sensation de satiete et une reduction ponderale |
WO2004056343A1 (fr) | 2002-12-19 | 2004-07-08 | Polymorfix, Inc. | Formulations ingerables pour la reduction transitoire non invasive du volume gastrique |
WO2007039294A2 (fr) * | 2005-10-05 | 2007-04-12 | Fmc Biopolymer As | Compositions de gelification et procedes |
WO2008022857A1 (fr) | 2006-08-24 | 2008-02-28 | Unilever N.V. | Composition liquide augmentant la satiété |
WO2008098579A1 (fr) | 2007-02-13 | 2008-08-21 | S-Biotek Holding Aps | Produit diététique comprenant de l'alginate |
DE102007026037A1 (de) * | 2007-06-04 | 2008-12-11 | Lts Lohmann Therapie-Systeme Ag | Gastroretentives System mit Alginat-Körper |
WO2011063809A1 (fr) * | 2009-11-24 | 2011-06-03 | S-Biotek Holding Aps | Produit minceur comprenant un alginate |
WO2011063817A2 (fr) * | 2009-11-26 | 2011-06-03 | D.Xign | Complément alimentaire permettant de réguler l'appétit |
WO2012163366A1 (fr) | 2011-06-03 | 2012-12-06 | S-Biotek Holding Aps | Composition contenant au moins un alginate et pouvant être utilisée dans le cadre du traitement et/ou de la prévention du surpoids |
-
2013
- 2013-09-03 WO PCT/DK2013/050278 patent/WO2014032676A1/fr active Application Filing
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6083540A (en) | 1995-07-14 | 2000-07-04 | Danisco A/S | Process for stabilizing proteins in an acidic environment with a high-ester pectin |
WO2003086360A1 (fr) | 2002-04-15 | 2003-10-23 | Beisel Guenther | Agent destine a generer une sensation de satiete et une reduction ponderale |
WO2004056343A1 (fr) | 2002-12-19 | 2004-07-08 | Polymorfix, Inc. | Formulations ingerables pour la reduction transitoire non invasive du volume gastrique |
WO2007039294A2 (fr) * | 2005-10-05 | 2007-04-12 | Fmc Biopolymer As | Compositions de gelification et procedes |
WO2008022857A1 (fr) | 2006-08-24 | 2008-02-28 | Unilever N.V. | Composition liquide augmentant la satiété |
WO2008098579A1 (fr) | 2007-02-13 | 2008-08-21 | S-Biotek Holding Aps | Produit diététique comprenant de l'alginate |
DE102007026037A1 (de) * | 2007-06-04 | 2008-12-11 | Lts Lohmann Therapie-Systeme Ag | Gastroretentives System mit Alginat-Körper |
WO2011063809A1 (fr) * | 2009-11-24 | 2011-06-03 | S-Biotek Holding Aps | Produit minceur comprenant un alginate |
WO2011063817A2 (fr) * | 2009-11-26 | 2011-06-03 | D.Xign | Complément alimentaire permettant de réguler l'appétit |
WO2012163366A1 (fr) | 2011-06-03 | 2012-12-06 | S-Biotek Holding Aps | Composition contenant au moins un alginate et pouvant être utilisée dans le cadre du traitement et/ou de la prévention du surpoids |
Non-Patent Citations (3)
Title |
---|
I. A. BROWNLEE; A. ALLEN; J.P. PEARSON; P.W. DETTMAR; M.E. HAVLER; M.R. ATHERTON ET AL.: "Alginate as a source of dietary fiber", CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, vol. 45, no. 6, 2005, pages 497 - 510 |
THAKUR ET AL., CRITICAL REVIEWS IN FOOD SCIENCE & NUTRITION, vol. 37, 1997, pages 47 - 73 |
VORAGEN ET AL.: "Food polysaccharides and their applications", 1995, MARCEL DEKKER, INC., pages: 287 - 339 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113423386A (zh) * | 2019-10-01 | 2021-09-21 | 美国倍利年制药有限公司 | 治疗或预防肥胖和体重管理的方法 |
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