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    • 专利摘要:
    The present invention relates to a composition comprising a combination of chitosan and a chitin-glucan copolymer. In particular, the invention relates to a pharmaceutical composition or a dietary supplement, particularly for oral administration, and a method of therapeutic treatment using these compositions.
    公开号:BE1024968B1
    申请号:E20175670
    申请日:2017-09-21
    公开日:2018-09-04
    发明作者:Véronique Maquet；Amore Salvatore Modica
    申请人:Kitozyme；
    IPC主号:
    专利说明:


    economy
    1024968 Bl
    FPS Economy, SMEs, Middle Classes & Energy Intellectual Property Office
    Date of issue: 04/09/2018
    PATENT
    Priority date: 09/23/2016
    International classification: A61K 31/716, A61K 31/722, A61P 1/14, A61P 3/04 Filing number: BE2017 / 5670 Filing date: 09/21/2017
    Holder:
    KitoZyme 4040, HERSTAL Belgium
    Inventor:
    MAQUET Véronique 4257 BERLOZ Belgium
    MODICAAMORE Salvatore 4420 SAINT-NICOLAS Belgium
    Composition of chitosan and chitin-glucan
    The present invention relates to a composition comprising a combination of chitosan and a chitin-glucan copolymer. In particular, the invention relates to a pharmaceutical composition or a food supplement, in particular for oral administration, and a method of therapeutic treatment using these compositions.
    BELGIAN INVENTION PATENT
    FPS Economy, SMEs, Middle Classes & Energy
    Publication number: 1024968 Deposit number: BE2017 / 5670
    Intellectual Property Office International Classification: A61K 31/716 A61K 31/722 A61P 1/14 A61P 3/04
    Date of issue: 04/09/2018
    The Minister of the Economy,
    Having regard to the Paris Convention of March 20, 1883 for the Protection of Industrial Property;
    Considering the law of March 28, 1984 on patents for invention, article 22, for patent applications introduced before September 22, 2014;
    Given Title 1 “Patents for invention” of Book XI of the Code of Economic Law, article XI.24, for patent applications introduced from September 22, 2014;
    Having regard to the Royal Decree of 2 December 1986 relating to the request, the issue and the maintenance in force of invention patents, article 28;
    Given the patent application received by the Intellectual Property Office on September 21, 2017.
    Whereas for patent applications falling within the scope of Title 1, Book XI of the Code of Economic Law (hereinafter CDE), in accordance with article XI. 19, §4, paragraph 2, of the CDE, if the patent application has been the subject of a search report mentioning a lack of unity of invention within the meaning of the §ler of article XI.19 cited above and in the event that the applicant does not limit or file a divisional application in accordance with the results of the search report, the granted patent will be limited to the claims for which the search report has been drawn up.
    Stopped :
    First article. - It is issued to
    KitoZyme, Hauts-Sarts Industrial Park Zone 2 Rue de Milmort 680, 4040 HERSTAL Belgium;
    represented by
    OFFICE KIRKPATRICK S.A., Avenue Wolfers 32, 1310, LA HULPE;
    a 20-year Belgian invention patent, subject to the payment of the annual fees referred to in article XI.48, §1 of the Code of Economic Law, for: Composition of chitosan and chitin-glucan.
    INVENTOR (S):
    MAQUET Véronique, Hamlet of Crenwick 29, 4257, BERLOZ;
    MODICAAMORE Salvatore, Rue Chantraine 108, 4420, SAINT-NICOLAS;
    PRIORITY (S):
    09/23/2016 FR 1658974;
    DIVISION:
    divided from the basic application: filing date of the basic application:
    Article 2. - This patent is granted without prior examination of the patentability of the invention, without guarantee of the merit of the invention or of the accuracy of the description thereof and at the risk and peril of the applicant (s) ( s).
    Brussels, 04/09/2018, By special delegation:
    BE2017 / 5670
    Composition of chitosan and chitin-glucan
    The present invention relates to a composition comprising a combination of chitosan and a chitin-glucan copolymer. In particular, the invention relates to a pharmaceutical composition or a food supplement, in particular for oral administration, and a method of therapeutic treatment using these compositions.
    Some biopolymers, especially natural fibers, regulate appetite and stimulate the feeling of satiety after absorption alone or in food. A person skilled in the art speaks of satiety products. For example, Wanders (Effects of dietary fiber we subjective appetite, energy intake and bodysuit weight: a systematic review of randomized controlled motocrosses, Obesity reviews on International 2011 Association for the Study of Obesity 12, 724-739) published a review of scientific studies concerning the effects of biopolymers on satiety. The satiating effect can lead to a loss of body mass via reduced appetite.
    There are a few commercial products for appetite reduction that are based on fibers having gel and viscous solution properties in an aqueous medium, for example in a gastric medium. Despite the multitude of dietary fibers available, glucomannan is an authorized polysaccharide known for its appetite reduction effects. Other fibers such as pectin, starch, gelatin, pea protein, arabinoxylans or alginates, are known for their more or less pronounced and demonstrated satiety effect.
    Prebiotics are nutrients (usually polysaccharides) that are consumed by probiotics (bacteria that are beneficial to human health). Humans cannot digest them, they arrive intact in the gut and probiotics can consume them. In absolute terms, they are not necessary for probiotics, but they can optimize their functioning and growth. Today, prebiotics are legion, it is also the case for example of inulin, an extract of chicory. Prebiotics are also naturally present in foods such as garlic, onions, asparagus, artichokes, bananas, oats or rye.
    There are therefore very many ingredients capable of being used in compositions, in particular pharmaceutical compositions for the reduction of caloric intake.
    BE2017 / 5670
    There are also numerous ingredients for the preparation of a composition, in particular pharmaceutical compositions or food supplements for the restoration of the intestinal flora.
    The present invention aims to solve the technical problem consisting in the supply of a composition, in particular a pharmaceutical composition, for the therapeutic treatment of a human being overweight or obese.
    The present invention aims to solve the technical problem consisting in the supply of a composition, in particular a pharmaceutical composition or a food supplement, for the reduction of caloric intake.
    The aim of the present invention is to solve the technical problem consisting in providing a composition, in particular a pharmaceutical composition or a food supplement, for the therapeutic treatment of excess body mass and / or control of body mass. of a human or animal.
    Another object of the present invention is to provide a composition for its use in a method of treatment of overweight or obesity, the most commonly used measure of which is the body mass index (BMI). According to the WHO, overweight corresponds to a BMI equal to or greater than 25 kg / m 2 ; and obesity at a BMI equal to or greater than 30 kg / m 2 .
    The aim of the present invention is to solve the technical problem consisting in the supply of a composition, in particular a pharmaceutical composition or a food supplement, for increasing satiety and / or reducing the body mass of a being. human or animal.
    The aim of the present invention is to solve the technical problem consisting in providing a composition, in particular a pharmaceutical composition or a food supplement, for the restoration of a healthy intestinal microflora of a human or animal being.
    The present invention aims to solve the technical problem consisting in the supply of a composition, in particular a pharmaceutical composition or a food supplement, to promote the intestinal comfort of a human or animal being.
    It has surprisingly been discovered by the inventors that a composition, in particular a pharmaceutical composition or a food supplement, comprising chitosan and a chitin-glucan copolymer can solve one or more of the above technical problems.
    Thus, the invention relates to a composition, in particular a pharmaceutical composition or a food supplement, comprising chitosan and a chitin-glucan copolymer.
    BE2017 / 5670
    The use of chitosan is known to promote the loss of body mass (see for example the studies of: Wadstein J, Thom E, Heldman E, Gudmundsson S, Lilja B: Biopolymer L112: a chitosan with fat binding properties and potential as a weight reducing agent. In Muzzarelli RA (ed): “Chitosan per os: from Dietary Supplement to Drug Carrier, '' Grottammare, Italy: Atec, 2000, pp65- 76; Cornelli U, Belcaro G, Cesarone MR, Cornelli M. Use of polyglucosamine and physical activity to reduce body weight and dyslipidemia in moderately overweight subjects. Minerva Cardioangiol. 2008, 56 (Suppl. 1, n ° 5): 71-78; AbelinJ, Lassus A. L112 Biopolymer - Fat binder as a weight reducer in patients with moderate ovesity. Medical Research report, 1994.) According to his studies, chitosan is used in doses ranging from 1.8 to 3 g per day, alone or in combination with other ingredients active ingredients to improve or supplement and the effectiveness of chitosan on ges tion of body mass. These are compositions used as part of a low-calorie diet, or not, or sports training.
    It is known from WO 2007/122187 (KitoZyme) that a chitin-glucan copolymer can be used in a composition administered orally, and in particular for its satiating effect. This activity would be associated with the water absorption capacity of the chitin-glucan copolymer. The results of a combination of chitosan and the chitin-glucan copolymer have never been mentioned since chitosan has lower water absorption (or water retention).
    Surprisingly, it has been discovered that the combination of chitosan and the chitin-glucan copolymer has a good satiating effect.
    Surprisingly, it has been found that the presence of chitin-glucan does not inhibit the lipid binding capacity of chitosan, but even improves the lipid binding capacity of chitosan. Those skilled in the art expected a decrease in this lipid binding capacity due to the presence of the chitin-glucan copolymer. Indeed, the chitin-glucan copolymer alone does not demonstrate any capacity for binding to lipids. However, the lipid binding capacity of a composition according to the invention is comparable to a composition comprising chitosan, despite the presence of the chitin-glucan copolymer in the composition of the invention.
    It has also been discovered a surprising effect of the combination of chitosan with the chitin-glucan copolymer on the viscosity in digestive conditions, because the viscosity is very high. The viscosity of the composition of the invention supports the satiating effect of the composition. Furthermore, the satiety effect hitherto recognized for chitin-glucan was appreciated for administration of chitosan at the rate of several grams per day. It has surprisingly been found that the composition according to the present invention
    BE2017 / 5670 provides a satiating effect at lower doses. There is therefore surprisingly a synergistic effect of the combination of chitosan and the chitin-glucan copolymer.
    Any type of chitosan can be used. The chitosan of the invention is advantageously of fungal origin, and preferably originating from the mycelium of a fungus of the Ascomycete type, and in particular from Aspergillus niger, and / or from a Basidiomycete fungus, and in particular Lentinula edodes ) and / or Agaricus bisporus. Alternatively, the fungus is Aspergillus niger. Alternatively, the fungus is Agaricus bisporus. The chitosan may be of GMO origin, but preferably is of non-GMO origin. A method for preparing chitosan is that described in PCT application WO03068824 (patents EP1483299; US 7,556,946), or also in PCT application WO 2011157955.
    The chitosan may have different molecular weights, generally ranging from 10,000 to 300,000. According to one variant, the average molecular weight is between 10,000 and 20,000. It is possible to hydrolyze chitosan in order to decrease its molecular weight. Preferably here, the average molecular mass is the average molecular mass in viscosity (Mv or average viscosimetric mass, calculated from the intrinsic viscosity according to the Mark-Houwink equation). The intrinsic viscosity is measured by capillary viscosimetry, with a capillary viscometer of the Ubbelohde type, according to the method of the monograph of the European Pharmacopoeia EP2.2.9. The flow time of the solution is measured through a suitable capillary tube (for example the Ubbelohde capillary tube 510 01 with a diameter of 0.53mm) using a viscometer of the SCHOTT brand, first at the initial concentration. in chitosan, then for several dilutions, for example according to the recommendations of method EP2.2.9. We deduce the reduced intrinsic viscosity for each of the concentrations. The reduced viscosity is brought as a function of the concentration, and the value is extrapolated to the concentration 0 to deduce the intrinsic viscosity. For example, the reduced viscosity (q red in ml / g) of the i dilutions must be taken as a function of the concentration C of the i dilutions (g / ml) according to formula 5.
    Formula 2. [q red ] = (ti -1 0 ) - (1 - C).
    To calculate the average viscosimetric mass, we apply the MarkHouwink equation with the constants k and alpha recommended by Rinaudo et al. (Int. J. Biol. Macromol, 1993, 15, 281-285), according to the DA (degree of acetylation) of chitosan, according to one of the following three formulas.
    Formula 3. Mv = ([η] / 0.082) (1 / ° '76) , for an AD of 2%;
    Formula 4. Mv = ([η] / 0.076) (1 / ° '76) , for a DA of 10% (for example 11.5%);
    Formula 5. Mv = ([η] / 0.074) (1 / ° '76) , for an AD of 20% (for example 21%).
    BE2017 / 5670
    For intermediate DA values, a linear interpolation is carried out to calculate the average viscosimetric mass (Mv).
    The chitosan advantageously has a controlled degree of acetylation. By the terms "chitosan having a controlled degree of acetylation" is meant a product whose degree of acetylation, that is to say the proportion of N-acetyl-glucosamine units, can be adjusted in a controlled manner.
    Preferably, the chitosan comprises a degree of acetylation (DA) of between 0 and 30 mol%. The degree of acetylation is the ratio of the number of N-acetyl-glucosamine units to the number of total monomers. The degree of acetylation of chitosan is determined by potentiometric titration which consists in determining the degree of acetylation of chitosan by titration of amino groups. It is based on the work of Rinaudo et al. (1999). Briefly, the chitosan is dissolved in an excess of dilute hydrochloric acid. Amine groups (on non-acetylated glucosamine units (G)) are positively charged (excess HCl)). The solution is then titrated with a dilute NaOH solution, using an automatic potentiometric titrator (KEM) and the pH is measured. In the first part of the reaction, the amount of excess HCI is determined. Next, the quantity of charged amine groups is determined: The titration curve shows two inflection points. The difference between the two volumes of NaOH makes it possible to know the amount of free amines.
    The chitosan of the invention is therefore insoluble in water. The term "insoluble in water" means a chitosan of which at least 90%, and preferably 95% (mass / mass), is not soluble in distilled water. In the examples, since chitosan is considered to be completely insoluble, the percentage of water-soluble matter can be compared to impurities.
    The border between chitosan and chitin generally corresponds to an AD of 50%: below this the compound is called chitosan, beyond, chitin.
    The chitosan is advantageously in the form of a powder. The chitosan powder is advantageously subject to a control of its particle size to ensure in particular the uniformity of the particle size of the powder. Thus it is preferred to control the particle size of the powder with preferably a reduction in the size of the particles, carried out for example by grinding,
    The inventors understand by “chitin-glucan” a copolymer consisting of links of the N-acetyl-D-glucosamine units and possibly of a minority proportion of the D-glucosamine units linked together by chains of type (1,6) of conformation alpha (chitin link), and of D-glucose units linked together by sequences of type (1,3), or (1,3) (1,6), or (1,3) (1,4 ), and preferably
    BE2017 / 5670 (1,3), of beta conformation (beta-glucan link, called here "glucan" or "glucan"). The term "chitin-glucan" is understood to mean a mixture of "chitin-glucan" copolymers, the degrees of polymerization of which, the respective units, the degree of acetylation and the molecular weights vary. Indeed, the “chitin-glucan” copolymer is preferably present in the form of a natural extract, it is generally present in the form of a mixture of different chitin-glucan copolymers (degrees of polymerization, the respective monomers, the degrees acetylation, molecular masses, etc.).
    Advantageously, at least 85% of the chitin part of the chitin-glucan copolymer are N-acetyl-D-glucosamine units, and at most 15% of this part are Dglucosamine units. Preferably, the chitin-glucan copolymer comprises at least 90% of N-acetyl-D-glucosamine units and at most 10% of D-glucosamine units.
    According to one embodiment, the ratio between chitin and beta-glucan is between 95: 5 and 5:95, preferably between 70:30 and 15:85, and more preferably between 60:40 and 20:80 (m / m).
    According to one variant, the chitin-glucan copolymer comprises from 20 to 30% of chitin and from 70 to 80% of beta-glucan (m / m).
    Advantageously, the chitin-glucan copolymer is present in the composition of the invention in the form of an extract, containing a chitin-glucan copolymer or a mixture, advantageously purified, of fungal source, and preferably of Aspergillus niger.
    The fungal extract can be obtained from the cell walls of fungal mycelia from different groups, including Zygomycetes, Basidiomycetes, Ascomycetes (of which Aspergillus niger is one) and Deuteromycetes and / or a mixture thereof. Said source of mushrooms must be chosen so as to allow the extraction of a chitin-glucan copolymer as defined above and below. There are sources of fungi which include glucans, but these units are soluble in water in particular, or contain little or no chains of chitin structure, and therefore do not allow the polysaccharide of the present invention to be obtained. The fungal source can be both natural and genetically modified (GMO).
    The copolymer is generally in the form of a white to slightly brown powder. It is essentially insoluble in aqueous and organic solvents whatever the temperature and the pH. It is able to swell in aqueous media. It is hygroscopic, generally able to absorb about 7 times its mass in water, which corresponds to the swelling capacity of insoluble plant fibers such as hemicellulose or pectin.
    BE2017 / 5670
    Advantageously, the chitin-glucan copolymer contains less than 10% of water-soluble compounds. Preferably, the chitin-glucan copolymer has a purity greater than 80%, and preferably greater than 85% by mass of copolymer relative to the total mass of the extract. Advantageously, the extract containing the chitin-glucan copolymer contains less than 40 mg / kg of heavy metals, as determined by the method described in the European Pharmacopoeia (monograph 2.4.8F), and advantageously less than 20 mg / kg of metals heavy. Advantageously, the extract containing the chitin-glucan copolymer contains less than 1 ppm of arsenic, as determined by ICP-MS. Advantageously, the extract containing chitin-glucan has a microbiological quality suitable for food use, and preferably contains less than 10,000 cfu / g, and preferably less than 1,000 cfu / g, for the total count of microorganisms, including including yeast and mold.
    Advantageously, the chitin-glucan copolymers according to the present invention are obtained by the process described in the international application WO 2007122187 filed on April 20, 2007, the French patent application FR 0651415 filed in the name of KITOZYME filed on April 21, 2006, in the application International WO 03/068824 and French patent application FR 0507066 also filed in the name of KITOZYME respectively on February 12, 2003 and July 4, 2005, which are incorporated here entirely by reference. This process is described in particular in application FR 0507066 pages 18, line 14, and following of the application as filed. Aspergillus niger is preferably used as a fungal source in this process.
    A preferred method comprises the following steps:
    1) suspend the biomass in an alkaline solution and remove the soluble compounds in an alkaline medium,
    2) purifying the insoluble product in an alkaline medium by treatment with water, and
    3) dry the water-insoluble product to obtain a powder, and
    4) optionally but preferably, control the particle size of the powder, preferably with a reduction in the size of the particles.
    More particularly, the composition according to the invention relates to a composition comprising a mass ratio of chitin-glucan relative to chitosan ranging from 0.01 to 10, and preferably from 0.1 to 5, and more preferably from 0.1 at 1.
    According to a particular variant, the composition according to the invention comprises a mass ratio of chitin-glucan copolymer (CG) relative to the total mass "CG + chitosan" ranging from 1/2 to 1/5, and preferably 1 / 4 to 2/5.
    BE2017 / 5670
    According to a particular variant, the composition according to the invention comprises a mass ratio of chitosan relative to the total mass "CG + chitosan" of 1/2 to 4/5, and preferably from 2/5 to 2/3 of chitosan , by mass compared to the total mass "CG + chitosan".
    According to a variant, the composition according to the invention comprises from 1% to 80% by mass of chitosan relative to the total mass of the composition.
    According to a variant, the composition according to the invention comprises from 5% to 80%, and preferably from 40 to 75%, by mass of chitosan relative to the total mass of the composition.
    According to a particular variant, the composition according to the invention comprises from 50% to 70% by mass of chitosan relative to the total mass of the composition. The term total mass of the composition is understood to mean the total mass of the composition comprising chitosan and chitin-glucan, in general in the form of a powder, compacted, compressed or not. Thus, if the composition is enclosed in a protective envelope, the mass of the protective envelope of the composition is not taken into account (for example for capsules or capsules).
    According to a variant, the composition according to the invention comprises from 1% to 80% by mass of chitin-glucan copolymer relative to the total mass of the composition.
    According to a variant, the composition according to the invention comprises from 5% to 60%, and preferably from 10 to 60%, by mass of chitin-glucan copolymer relative to the total mass of the composition.
    According to a particular variant, the composition according to the invention comprises from 30% to 45% by mass of chitin-glucan copolymer relative to the total mass of the composition.
    For example, the composition has a mass ranging from 100 to 2500 mg, and preferably has a mass ranging from 200 to 1500 mg.
    According to one embodiment, the composition according to the invention comprises a mass of chitin-glucan copolymer ranging from 25 to 1000 mg, and for example from 100 to 500 mg ,. According to a particular embodiment, the composition according to the invention comprises approximately 250 mg or 375 mg of chitin-glucan copolymer.
    According to one embodiment, the composition according to the invention comprises a mass of chitosan ranging from 75 to 2000 mg, and for example from 200 to 1000 mg. According to a particular embodiment, the composition according to the invention comprises approximately 415 mg or 625 mg of chitosan.
    According to a variant, the composition in mixture with vegetable oil (for example olive oil) has a viscosity ranging from 600 to 5000 cP measured in
    BE2017 / 5670 phosphate buffered saline at acidic pH. For the viscosity measurement method: the mixture between the product and the oil is taken with a spatula and introduced into the chamber of the Brookfield type viscometer (for example: DV-II + pro Brookfield) by adjusting the pH to 5. The viscosity of the complex is measured with an S34 spindle, starting with a speed of 100RPM and adjusting / decreasing this speed in order to be in the reading range of the device.
    According to an advantageous variant, the viscosity of the mixture formed between the product and the oil in an aqueous medium at 25 ° C is greater than 1000cP, and preferably greater than 1500cP, and more preferably 1800 cP.
    The invention also relates to a composition in the form of capsules.
    According to another variant, the composition of the invention is in the form of tablets, such as for example film-coated tablets or effervescent tablets.
    According to another variant, the composition of the invention is in the form of powder sticks
    According to a variant, the composition according to the invention is to be dissolved in a hot or cold drink.
    According to a variant, the composition according to the invention is to be incorporated into a food matrix ,.
    Preferably, the composition of the invention is dry.
    According to one embodiment, the composition according to the invention consists solely of a combination of chitosan and a chitin-glucan copolymer without any other ingredient in the composition.
    According to one embodiment, the composition of the invention can also comprise one or more excipients and / or pharmaceutically active ingredients, and / or in particular can comprise one or more other biopolymers and / or other fibers than chitosan and chitin- glucan.
    Advantageously, the composition comprises one or more additional fibers chosen from: tara gum, xhantan gum, gum arabic, alginate, oligofructose, fructo-oligosaccharide, arabinoxylan, inulin, polydextrose, pectin, carrageenan, carboxymethylcellulose, sugar beet fiber, fiber wheat, and any of their mixtures.
    In general, the excipients are chosen from:
    maltodextrin, sillice dioxide, magnesium stearate, cellulose, hypromellose, polyethylene glycol, croscarmellose, sucralose, flavor, and any of their mixtures.
    BE2017 / 5670
    According to one aspect the invention relates to an article, for example in the form of water-soluble sachets, tablets, film-coated tablets; effervescent tablets, or capsules, comprising a composition according to the invention
    The invention also relates to a process for preparing a composition.
    For example, the composition according to the invention can comprise the mixture of a chitosan powder and a chitin-glucan copolymer powder. According to one embodiment, the composition is in powder form
    According to a preferred embodiment, the composition according to the invention is for pharmaceutical use.
    In one aspect, the invention relates to a pharmaceutical composition according to the invention for use in a method of treating overweight or obesity of a subject in need thereof. We generally speak of a pharmaceutical composition when the composition is administered as part of a therapeutic treatment.
    According to one embodiment, the composition according to the invention is a food supplement.
    According to one embodiment, the composition according to the invention is a medical device.
    According to one aspect, the invention relates to a composition, in particular a pharmaceutical composition or a food supplement, and in particular relates to a medical device, for its use in a method of treatment of a human being having a BMI equal to or greater than 25 kg / m 2 and less than 30 kg / m 2 .
    According to one aspect, the invention relates to a composition, in particular a pharmaceutical composition or a food supplement, and in particular relates to a medical device, for its use in a method of treatment of a human being having a BMI equal to or greater than 30 kg / m 2 .
    According to one aspect, the invention relates to a composition, in particular a pharmaceutical composition or a food supplement, and in particular relates, for its use in a method of treatment of a human being having a BMI equal to or greater than 35 kg / m 2 and in particular a BMI less than or equal to 40 kg / m 2 (we generally speak of severe obesity).
    According to one aspect, the invention relates to a composition, in particular a pharmaceutical composition or a food supplement, and in particular relates, for its use in a method of treatment of a human being having a BMI greater than 40 kg / m 2 (we generally speaking of morbid or massive obesity).
    More particularly, the invention relates to a composition according to the invention in form which can be administered orally.
    BE2017 / 5670
    The invention also relates to a composition according to the invention for its use in a method of therapeutic treatment of a human being.
    The invention relates in particular to a composition according to the invention for its use in a method of therapeutic treatment of an overweight or obese human being, the overweight and obesity being characterized by a Body Mass Index (BMI) ) equal to or greater than 25 and 30, respectively.
    The invention relates in particular to a composition defined according to the invention for its use in a method of therapeutic treatment of caloric intake, and in particular for the reduction of caloric intake, in a human being.
    Advantageously, the composition according to the invention is used in a method of therapeutic treatment of excess body mass and / or control of the body mass of a human being.
    Advantageously, the composition according to the invention is used for increasing satiety and / or reducing body mass, in particular for capturing fat and / or preventing food cravings in a human being in a treatment method. therapy of a human being.
    According to one embodiment, the composition according to the invention is used in a method of therapeutic treatment for restoring a healthy intestinal microflora of a human being or in a method of therapeutic treatment for promoting the intestinal comfort of a human being.
    The present invention also relates to a method for improving the feeling of satiety, limiting cravings, regulating or controlling appetite, promoting or increasing the loss of body mass, controlling or regulating overweight body, reducing caloric intake, preventing cravings, restore a healthy intestinal microflora, or promote intestinal comfort, in particular of a human or animal being, and more specifically of a human being.
    The present invention also relates to the non-therapeutic oral use of a combination of chitosan and of a chitin-glucan copolymer to improve the feeling of satiety, to capture fat, to limit cravings, to regulate or control appetite, to promote or increase the loss of body mass, control or regulate overweight, reduce caloric intake, prevent cravings, restore a healthy intestinal microflora, or promote intestinal comfort.
    The present invention also relates to the use of a combination of chitosan and of a chitin-glucan copolymer for the preparation of a composition, in particular of a pharmaceutical composition or a food supplement, according to the invention.
    BE2017 / 5670
    The invention also relates to the use of a pharmaceutical composition for the treatment of a disease or pathology as described in the invention.
    The invention also relates to the use of a composition as defined according to the invention comprising chitosan and a chitin-glucan copolymer for non-therapeutic use.
    The present invention also relates to the treatment of one or more of the gastrointestinal symptoms, and in particular of abdominal pain, discomfort, bloating, abdominal distension, flatulence, intestinal difficulties in defecation, and / or a feeling of incomplete bowel movement, especially in an overweight or obese subject.
    More particularly, the combination of chitosan and a chitin-glucan copolymer is suitable for use by the oral route (in the form which can be administered by the oral route) as a pharmaceutical composition or as a food supplement or medical device.
    According to a variant, the combination of chitosan and a chitin-glucan copolymer is incorporated in the form of a powder in a food, typically a food liquid.
    According to a variant, a composition according to the invention is administered once a day.
    Advantageously, a composition according to the invention can be administered several times a day, for example 2, 3, or 4 times a day and preferably before each meal.
    According to a variant, a composition according to the invention is administered twice a day.
    According to a variant, a composition according to the invention is administered 3 times a day.
    One can for example administer a composition according to the invention just before meals.
    It is preferred to administer a daily dose of 800 to 3000 mg, and for example 2500 mg, of chitosan and 500 to 1800, for example 1500 mg, of chitin-glucan.
    The present invention also relates to a method of therapeutic treatment comprising the administration to a subject, in particular a human being, needing an effective amount of a composition according to the invention.
    The term “composition according to the invention” or equivalent terms means a composition defined as in the present invention, including according to any one of the variants, particular or specific embodiments, independently or according to any one of combinations thereof, including according to preferred characteristics. When the invention refers to a therapeutic use, the terms "composition according to the invention" or equivalent terms also refer to a "composition
    BE2017 / 5670 pharmaceutical ”or therapeutic as defined in the invention. When the invention refers to a non-therapeutic use, the terms “composition according to the invention” or equivalent terms refer to all the embodiments of the invention, including according to any one of the variants, modes of particular or specific production, independently or according to any one of their combinations, including food supplement compositions.
    The terms "one" or "one" refer to one or more unless otherwise indicated.
    Other objects, characteristics and advantages of the invention will become apparent to a person skilled in the art after reading the explanatory description which refers to examples which are given only by way of illustration and which cannot be in no way limit the scope of the invention.
    The examples form an integral part of the present invention and any characteristic which appears new compared with any prior state of the art from the description taken as a whole, including the examples, forms an integral part of the invention in its function and in its generality.
    Thus, each example is general in scope.
    On the other hand, in the examples, all the percentages are given by mass, unless otherwise indicated, and the temperature is expressed in degrees Celsius unless otherwise indicated, and the pressure is atmospheric pressure, unless otherwise indicated.
    EXAMPLES
    Example 1 Effect of a composition according to the invention on the absorption of lipids
    1.1. Qualitative method
    The lipid absorption capacity of a composition of the invention combining chitosan and chitin-glucan fibers is measured as described below.
    A given quantity of a composition according to the invention (Example 1) is dissolved in a 0.1 N HCl solution.
    Olive oil is added to the solution thus obtained to achieve two oil / mixture mass ratios:
    800/1
    1800/1
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    The pH of the mixture is then adjusted to 2 and incubated for 2 hours at 37 ° C to reproduce the gastric conditions. A phosphate buffer solution is then added to the sample and the pH is adjusted to 7 by adding NaOH to simulate the intestinal pH.
    After 30 minutes of incubation at 37 ° C, the sample is centrifuged for 25 minutes at 100 rpm. The test result is considered to be in conformity when at least 2 out of 3 replicas are in conformity, that is to say absorb in satisfactory quantity the lipids present.
    Description of the samples • FS represents 500 mg of the composition according to the present invention: 187.5 mg of chitin-glucan (KiOnutrime-CG; Kitozyme, Belgium) and 312.5 mg of chitosan (KiOnutrime-CsG; Kitozyme, Belgium);
    • Positive control: 500 mg of KiOnutrime-CsG (Kitozyme, Belgium);
    • Negative control: 500 mg of KiOnutrime-CG (Kitozyme, Belgium).
    Table 1:
    o Oil / mixture ratio = 800/1
    Sample Test 1 Test 2 Test 3 TestRESULT FS PASS PASS PASS PASS Controlpositive PASS PASS PASS PASS Controlnegative FAIL / / FAIL
    Table 1a o Oil / mixture ratio = 1800/1
    Sample Test 1 Test 2 Test 3 TestRESULT FS PASS PASS PASS PASS Controlpositive PASS PASS PASS PASS Controlnegative FAIL / / FAIL
    PASS: the test gives a consistent result;
    FAIL: The test does not give a consistent result.
    BE2017 / 5670
    It is noted that the composition according to the invention conforms according to the above tests and therefore allows the absorption of lipids.
    1.2. Quantitative method
    The lipid absorption capacity of a composition of the invention combining chitosan and chitin-glucan fibers (Composition A, according to composition FS) is measured as described below and compared with a composition based on chitosan only (Composition B).
    1g of a composition (A or B) (called in the formula below "test sample", expressed in grams (g)) is dissolved in 100 mL of a 0.16N HCl solution. After vigorous stirring, the solution is left to stand for 30 min. 10 ml of solution are taken and placed in 10 tubes (numbered from 1 to 10) to which are added 10g of oil. The mixture is agitated with an ultraturax for 30 seconds at 13,000 rpm. Each tube is capped and the sample is left to stand for 30 min at room temperature. 10 ml of carbonate buffer are added to each tube which is then placed under a rotary shaker at 75 rpm for 10 min. The sample is then centrifuged at 17000g for 2 minutes and cooled in the freezer to -20 ° C to promote phase separation. The oily phase is then collected and weighed in order to deduce therefrom the% of fat binding capacity ("fat binding capacity" or "FBC") using the following formula:
    FAT-BINDING CAPACITY (FBC) (%) = ((total oil (g) - unbound oil (g)) / test portion (g)) x 100
    Results
    Composition A(invention) BCF (%) Composition B(comparative) BCF (%) Tube 1 5385 Tube 1 6356 Tube 2 6212 Tube 2 6047 Tube 3 7415 Tube 3 3877 Tube 4 5955 Tube 4 4320 Tube 5 6574 Tube 5 3839 Tube 6 5245 Tube 6 3995 Tube 7 4556 Tube 7 4469
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    Tube 8 3342 Tube 8 4645 Tube 9 2757 Tube 9 3544 Tube 10 ND 2823 Average 5271 Average 4392 Standard deviation 1509 Standard deviation 1084 RSD (%) 28.6 RSD (%) 24.7
    RSD: "relative standard deviation" (coefficient of variation or relative standard deviation)
    It is noted that the composition according to the invention advantageously has a percentage of fat binding capacity greater than that of the composition based on chitosan alone, which is surprising.
    Example 2 Effect of the Gastric pH Combination on Lipid Absorption and Viscosity
    The lipid absorption capacity of a composition of the invention is measured as described in Example 1, with only an oil / mixture ratio of 800/1. The exception is that the pH is adjusted to 5 and not 7, in order to mimic the intestinal pH in the presence of the food bolus. Then the viscosity of the oil / mixture complex is measured. The result is presented in Table 2.
    Description of the samples • FS represents 500 mg of the composition according to the present invention: 187.5 mg of chitin-glucan (KiOnutrime-CG; Kitozyme, Belgium) and 312.5 mg of chitosan (KiOnutrime-CsG; Kitozyme, Belgium);
    • Positive control: 500 mg of KiOnutrime-CsG (Kitozyme, Belgium);
    • Negative control: 500 mg of KiOnutrime-CG (Kitozyme, Belgium).
    Table 2:
    Sample RESULT capacitylipid binding Viscosity RESULT(cP) FS test 1 PASS 1987 FS test 2 PASS 2202 FS test 3 PASS 2178 Positive control test 1 PASS 3980
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    Test 2 positive control PASS 4143 Positive control test 3 PASS 4152 Negative control test 1 FAIL 67.2 Negative control test 2 FAIL 67.2 Negative control test 3 FAIL 67.2
    The viscosity is evaluated according to the protocol described above.
    Example 3 - Effect of the combination on the water retention capacity
    The method is based on the method used by Quinn and Paton (J.R. Quinn, R. Paton - A practical measurement of water hydration capacity of protein materials. June 20, 1978):
    - Each tube (with cap) is weighed (mass 1) and identified.
    - Each tested sample is weighed (mass 2) and put in a tube.
    mL of RO water is added to each tube.
    - Each tube is shaken vigorously, until homogenized. Each tube is topped with reverse osmosis water.
    - All the tubes are centrifuged at 4000RPM for 10 minutes.
    - The supernatants are removed using a Pasteur pipette and each tube is weighed with a stopper (mass 3).
    The difference [Mass 4 = mass 3 - mass 2 - mass 1] is the amount of water retained by the sample.
    The water retention capacity is calculated by the ratio [mass 4 / mass 2], and 20 expressed in mL of water per gram of sample.
    Description of the samples • FS represents 500 mg of the composition according to the present invention: 187.5 mg of chitin-glucan (KiOnutrime-CG; Kitozyme, Belgium) and 312.5 mg of chitosan (KiOnutrime-CsG; Kitozyme, Belgium);
    • CS: 500 mg of KiOnutrime-CsG (Kitozyme, Belgium);
    • CG: 500 mg of KiOnutrime-CG (Kitozyme, Belgium).
    Table 3:
    Sample Retention capacity
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    water (mg / gr) CG test 1 5.9 CG test 2 6.0 CG test 3 6.0 CS test 1 3.0 CS test 2 3.0 CS test 3 3.0 FS test 1 4.3 FS test 2 4.0 FS test 3 3.7
    Based on the water holding capacity (or WHC; “water holding capacity”), one could expect a loss of the satiating effect because the WHC of the combination according to the invention chitin-glucan / chitosan is lower than that of chitin-glucan alone: approximately 4X its weight in water for the combination against 6X its weight in water for chitin-glucan; it was therefore not easy to maintain this satiating effect. In the case of a composition according to the invention, this effect is brought about by the viscosity of the oil / {chitineglucan / chitosan} complex, while the chitin-glucan alone does not capture any fat (cf. example 2).
    Thus, the compositions according to the invention are in particular capable of capturing fats, of reducing body mass, of promoting or increasing loss of body mass, of controlling or regulating overweight, of reducing caloric intake, of restoring a healthy intestinal microflora, promote intestinal comfort, prevent food cravings, regulate or control appetite.
    Example 4 - Use study under medical supervision
    A 4-week study was carried out on 22 women aged 18 to 50 with a Body Mass Index (BMI) of 25 to 30, suffering from mild to moderate intestinal disorders (patients). Complaints related to different types of gastrointestinal symptoms, including bloating, gas, constipation, abdominal pain and dyspepsia, have been assessed.
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    The study was carried out under medical supervision of doctors who diagnosed the symptoms when enrolled in the study and at the end of the study at 4 weeks. Patients also assessed their symptom complaints during the study.
    The treatment administered was 6 capsules per day at a rate of 2 capsules 3 times per day, each capsule containing 417 mg of chitosan and 250 mg of chitin-glucan.
    The study supports satisfactory results (6.5 / 10) with improved digestive comfort (6.7 / 10) and weight loss (average at -2.2 kg /).
    The monitoring of complaints related to symptoms by doctors and patients therefore shows a positive action of a composition according to the invention.
    There is a rapid effect on digestive symptoms, with in particular a feeling of digestive well-being thanks to improved transit and a feeling of "deflation".
    Weight loss is rapid (on average from the 2nd week) and gradual.
    The digestive action is supported by the study (which is demonstrated by a marked improvement in complaints related to the symptoms present at inclusion) with a rapid action on the initial symptoms and on well-being at this level.
    BE2017 / 5670
    权利要求:
    Claims (19)
    [1]
    1. Pharmaceutical composition comprising chitosan and a chitin-glucan copolymer.
    [2]
    2. - Pharmaceutical composition according to claim 1, characterized in that it comprises a mass ratio of chitin-glucan relative to chitosan ranging from 0.01 to 10, and preferably from 0.1 to 5, and more preferably 0.1 to 1.
    [3]
    3. - Pharmaceutical composition according to claim 1 to 2, characterized in that it has a mass ranging from 100 to 2500 mg.
    [4]
    4. - Pharmaceutical composition, according to any one of claims 1 to 3, characterized in that the composition has a mass ranging from 200 to 1500 mg.
    [5]
    5. - Pharmaceutical composition according to any one of claims 1 to 4, characterized in that the composition is in powder form.
    [6]
    6. - Pharmaceutical composition according to any one of claims 1 to 5, in form which can be administered orally.
    [7]
    7. - Pharmaceutical composition according to any one of claims 1 to 6, for its use in a method of therapeutic treatment of a human being.
    [8]
    8. - Pharmaceutical composition according to claim 7, for its use in a method of therapeutic treatment of a human being overweight or obese, overweight and obesity being characterized by a Body Mass Index (BMI) equal to or greater than 25 and 30, respectively.
    [9]
    9. - Pharmaceutical composition, according to claim 7 or 8, for its use in a method of therapeutic treatment of caloric intake, and in particular for the reduction of caloric intake, in a human being.
    [10]
    10. - Pharmaceutical composition, according to any one of claims 7 to 9, for its use in a method of therapeutic treatment of excess body mass and / or control of the body mass of a human being.
    BE2017 / 5670
    [11]
    11. - Pharmaceutical composition, according to any one of claims 7 to
    10, for its use for increasing satiety and / or reducing body mass and / or for capturing fat and / or preventing food cravings in a human being in a method of therapeutic treatment of a human being human.
    [12]
    12. - Pharmaceutical composition, according to any one of claims 7 to
    11, for use in a therapeutic treatment method for restoring a healthy intestinal microflora of a human being.
    [13]
    13. - Pharmaceutical composition according to any one of claims 7 to
    12, for use in a method of therapeutic treatment to promote the intestinal comfort of a human being.
    [14]
    14, - Article, for example in the form of water-soluble sachets, tablets, film-coated tablets, effervescent tablets, or capsules, comprising a pharmaceutical composition as defined in any one of claims 1 to 13.
    [15]
    15. Non-therapeutic oral use of a combination of chitosan and a chitin-glucan copolymer to improve the feeling of satiety, capture fat, limit cravings, regulate or control appetite, promote or increase the loss of body mass, control or regulate excess body weight, reduce caloric intake, prevent food cravings, restore a healthy intestinal microflora, or promote intestinal comfort.
    [16]
    16. - Non-therapeutic use according to claim 15, characterized in that the combination of chitosan and of a chitin-glucan copolymer has a mass ratio of chitin-glucan with respect to chitosan ranging from 0.01 to 10, and preferably from 0.1 to 5, and more preferably from 0.1 to 1.
    [17]
    17 - Non-therapeutic use according to claim 15 or 16, characterized in that the combination of chitosan and of a chitin-glucan copolymer is used in the form of a composition having a mass ranging from 100 to 2500 mg, and preferably from 200 to 1500 mg.
    2017/5670
    BE2017 / 5670
    [18]
    18.- Non-therapeutic use any one of claims 15 to 17, characterized in that the combination of chitosan and a chitin-glucan copolymer is used in powder form.
    19. The non-therapeutic use of any one of claims 15 to 18, characterized in that the combination of chitosan and of a chitin-glucan copolymer is used in form which can be administered orally.
    2017/5670
    [19]
    23 BE2017 / 5670
    SHORT
    Composition of chitosan and chitin-glucan
    The present invention relates to a composition comprising a combination of 5 chitosan and a chitin-glucan copolymer. In particular, the invention relates to a pharmaceutical composition or a food supplement, in particular for oral administration, and a method of therapeutic treatment using these compositions.
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    同族专利:
    公开号 | 公开日
    BE1024968A1|2018-08-29|
    FR3056402A1|2018-03-30|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US20070299034A1|2002-02-12|2007-12-27|Marie-France Versali|Cell wall derivatives, their preparation process, and use thereof|
    EP2865278A1|2012-06-25|2015-04-29|Damm S.a.|Fat binder obtained from biomass resulting from beer production|
    WO2021046073A1|2019-09-05|2021-03-11|Dupont Nutrition Biosciences Aps|Feed composition|
    FR3105729A1|2019-12-31|2021-07-02|MRS-Biotech|Composition for weight management of a subject|
    法律状态:
    2018-10-25| FG| Patent granted|Effective date: 20180904 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1658974A|FR3056402A1|2016-09-23|2016-09-23|COMPOSITION OF CHITOSAN AND CHITINE-GLUCAN|
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