WO2014184435A1 - Cystéine ou dérivé associé pour le traitement de la gastrite atrophique - Google Patents

Cystéine ou dérivé associé pour le traitement de la gastrite atrophique Download PDF

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Publication number
WO2014184435A1
WO2014184435A1 PCT/FI2014/050351 FI2014050351W WO2014184435A1 WO 2014184435 A1 WO2014184435 A1 WO 2014184435A1 FI 2014050351 W FI2014050351 W FI 2014050351W WO 2014184435 A1 WO2014184435 A1 WO 2014184435A1
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Prior art keywords
composition according
cysteine
composition
active agent
months
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PCT/FI2014/050351
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English (en)
Inventor
Osmo Suovaniemi
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Biohit Oyj
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Application filed by Biohit Oyj filed Critical Biohit Oyj
Priority to EP14797478.6A priority Critical patent/EP2996687A4/fr
Priority to EA201591994A priority patent/EA201591994A1/ru
Priority to CN201480039914.7A priority patent/CN105492002A/zh
Publication of WO2014184435A1 publication Critical patent/WO2014184435A1/fr
Priority to HK16111568.1A priority patent/HK1223284A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Definitions

  • the present invention concerns a pharmaceutically acceptable composition containing a cysteine (either as L- or D-cysteine) or N-acetyl cysteine for the treatment of atrophic gastritis (in the corpus or antrum, or in both), using a specific dosage regimen.
  • a cysteine either as L- or D-cysteine
  • N-acetyl cysteine for the treatment of atrophic gastritis (in the corpus or antrum, or in both), using a specific dosage regimen.
  • Atrophic gastritis is a chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues.
  • Helicobacter pylori (H. pylori) infection is, in turn, the main pathogenic factor leading to atrophic gastritis (AG), which in turn is the single most important risk factor for carcinoma of the stomach (or gastric cancer).
  • AG atrophic gastritis
  • treatments of H. pylori infections are generally unsuccessful in treating the atrophic gastritis, the latter is generally considered to be an incurable disease, particularly if it has developed fully (i.e. is chronic).
  • WO2012143608 a solution to the said problem is offered by including in the treatment of said H. pylori patients administration of a composition containing a semi-essential amino acid, cysteine, for 1-4 weeks duration.
  • this treatment does not target the atrophic gastritis, which is not uncommon in the patients suffering from an H. pylori infection.
  • Atrophic gastritis alone, is a well-known risk factor for gastric and esophageal cancer. About 1,469,000 cases of these cancer types are reported globally every year, i.e. they constitute almost 10% of all cancers. However, the curing rates of gastric and esophageal cancer are low.
  • Said type of gastritis is chronic and affects the mucosa of gastric corpus or antrum or both (i.e., corpus-antrum- or pangastritis). It is characterized histologically by chronic inflammation of the gastric mucosa with loss of glandular cells and replacement by intestinal-type epithelium (intestinal metaplasia) and fibrous tissue. Clinically, it is characterized by hypo- or achlorhydria and loss of intrinsic factor (IF) resulting in pernicious anemia.
  • IF intrinsic factor
  • both atrophic gastritis and H. pylori infections can be diagnosed based on the levels of stomach-specific biomarkers in the blood.
  • the conventional treatments for these conditions are not the same.
  • atrophic gastritis is mainly caused by H. pylori infections, it is not necessarily cured upon eradication of H. pylori.
  • autoimmune disorders include autoimmune disorders, pernicious anemia (PA) and achlorhydria, both leading to microbial colonization of the stomach. This can also take place after eradication of H. pylori. There are considered to be about 500 million people in the world suffering from atrophic gastritis / an achlorhydric stomach.
  • microbes formed in the stomach as a result of achlorhydria are able to produce significant amounts of acetaldehyde by oxidation from ingested alcohol. Under anaerobic conditions, these microbes are able to produce acetaldehyde also from glucose.
  • Acetaldehyde present in alcoholic beverages and formed from ethanol endogenously has been classified by I ARC as Group 1 carcinogen in humans.
  • Acetaldehyde can be eliminated from saliva or the stomach after alcohol intake and during smoking using a semi-essential amino acid, cysteine, particularly in the form of L-cysteine. More specifically, it has been shown that a formulation releasing e.g. L-cysteine in a controlled manner (e.g. the formulation known as Acetium ® ) can be used to decrease the acetaldehyde concentration formed during alcohol exposure, thus minimizing the exposure to carcinogenic acetaldehyde (as described in EP 1339394). However, this decrease of acetaldehyde concentration is targeted only to the time period during alcohol exposure, whereby the effect is short-term (a couple of hours in an optimal situation), and the dose is designed only for this immediate need.
  • a formulation releasing e.g. L-cysteine in a controlled manner e.g. the formulation known as Acetium ®
  • this decrease of acetaldehyde concentration is targeted only to the time period during alcohol exposure, whereby the
  • Another objective of the present invention is to develop a dosage regimen of a
  • This invention is based on the finding that a semi-essential amino acid, cysteine, in the form of either L- or D-cysteine (or as N-acetylcysteine), is capable of reverting (or healing, or inducing recovery of) atrophic gastritis, both in the corpus and in the antrum, when administered during a sufficient period of time.
  • the present invention concerns a pharmaceutically acceptable composition containing one or more cysteines (selected among L-cysteine, D-cysteine and N-acetylcysteine), for use in treating AG (or an H. pylori infection), when administered in a dose of 300 to 1500 mg per day during a period of at least 2 months, often up to 2 years, and possibly for longer, preferably using a reduced dose after the first 2 - 12 months.
  • compositions and the dosage regime of the present invention are characterized by what is stated in the characterizing part of Claim 1.
  • composition in the used dose has the advantage of being completely harmless to the subject.
  • the present invention concerns a pharmaceutically acceptable composition containing a semi-essential amino acid, cysteine, particularly L-cysteine, D-cysteine or N- acetylcysteine, or a combination of 2 or 3 of these, as an active agent, for use in treating atrophic gastritis (AG) in a subject with a dose of 300 to 1500 mg per day, administered to the subject for at least 2 months.
  • a semi-essential amino acid cysteine
  • cysteine particularly L-cysteine, D-cysteine or N- acetylcysteine
  • a combination of 2 or 3 of these as an active agent
  • the subjects likely to benefit from the said treatment can be sorted out using a histological sample obtained by gastroscopy, but preferably the diagnosis is carried out using a noninvasive bio marker test (such as the GastroPanel® test) on samples of body fluid (preferably blood samples) collected among selected subjects (preferably being subjects at risk for AG and its complications).
  • a noninvasive bio marker test such as the GastroPanel® test
  • stomach-specific markers such as the biomarkers of the GastroPanel® test.
  • Said subjects can be either human or animal patients, preferably human patients.
  • the said treatment for documentation of the long-term efficacy and for control of eventual recurrence, it is preferred to continue the said treatment (with the said composition) for 3-, 4-, or 6 months, or up to 2 years, even after a negative biomarker test result, possibly with declining cysteine dose of 300 to 900 mg per day, after the first 6 months.
  • the composition may also contain other active agents, e.g. conventional antibiotics, chelating agents and alpha-hydroxy acids (HICAs), or other acids (such as betaine hydrochloride or glutamic acid), or pepsin or both, to relieve any conditions related to an achlorhydric stomach and/or H. pylori infection, and with a further intention to prevent the conversion of cysteine to less reactive cystine.
  • active agents e.g. conventional antibiotics, chelating agents and alpha-hydroxy acids (HICAs), or other acids (such as betaine hydrochloride or glutamic acid), or pepsin or both, to relieve any conditions related to an achlorhydric stomach and/or H. pylori infection, and with a further intention to prevent the conversion of cysteine to less reactive cystine.
  • the composition is preferably formulated into monolithic or multi-particular tablets, capsules, lozenges, chewing gums, or granules as such, or into the physical structure of a gel.
  • the formulation is intended to provide a local action by delivering the active agent(s) to its(their) desired site of action, i.e., the stomach.
  • at least one of the carriers of the composition will be selected among those known to facilitate controlled, and particularly sustained release of the active agent(s).
  • carrier here also includes fillers and binders.
  • the optimal carriers are preferably selected among those capable of maintaining an effective concentration of the pharmaceutically active agent(s) in the stomach during a period of at least 30 minutes using one unit dose, targeting AG, preferably as a mono therapy.
  • the used carriers are selected from those capable of controlling the releasing speed of the active agent(s) so that these compounds are released, locally, in the stomach during a period of 60-120 minutes.
  • examples of such carriers are substances, which are selected from the group of various chitosans, alginates, such as sodium alginate, aluminium hydroxide, sodium
  • carboxymethyl cellulose sodium hydrogen carbonate, and enteric polymers, preferably from enteric polymers.
  • enteric polymers preferably from enteric polymers.
  • Such carriers may be used either alone, particularly when the intended release time is 30-60 minutes, or as combinations of two or more substances, in cases when the intended release times exceed 60 minutes.
  • a single unit, or formulation, of the composition preferably comprises 50-500mg, more preferably between 50-300mg, and most suitably between 100-200mg of the cysteine(s), whereby the required daily dose of cysteine can be provided using one or more units or formulations, preferably 2-6 units or formulations per day.
  • the "unit” or “formulation” may implicate one tablet, capsule, lozenge or chewing gum, or one measurable unit of a gel or a gel-forming liquid.
  • the optional further active agent(s) can be added to the formulation in amounts of 1 to 50 weight-% of the total amount of active agent(s), preferably 10 to 40 weight-%, most suitably 20 to 30 weight-%.
  • the composition according to the invention which releases its contents in the stomach, contains at least one - preferably two - polymers, in the form of additives, such as carriers, fillers or binders, which have the task of keeping the formulations (and the active agent(s)) as long as possible, for two hours minimum, in the stomach, generally by forming a gel that floats in the contents of the stomach.
  • a specific task of the polymers is to prolong the release of the active agent(s).
  • the composition is preferably in the form of an encapsulated composition comprising a mixture of powder or granules that form a gel in the stomach.
  • the composition comprises said polymers and optional further additives. This encapsulated composition is most suitably formulated to be swallowed by the subject.
  • the amount of such polymers in the composition is preferably 10-50%, preferably 15-40%, and most preferably 20-30%.
  • cysteine(s) in the composition are mixed with the fillers needed and, after that, granulated by using enteric polymers as binders.
  • the composition can include, for example granules contained in an HPMC capsule, the granules containing a suitable filler and a suitable binder, as well as, optionally, further conventional pharmaceutical additives.
  • An exemplary granule composition might contain:
  • a particularly preferred active agent is L-cysteine.
  • the used carriers are selected among those that are capable of controlling the releasing speed of the active agent(s) so that these compounds are released, locally, in the mouth during a period of 60-120 minutes.
  • the release will be controlled also by the conditions in the mouth.
  • Examples of carriers suitable for this kind of formulations include substances, which are selected from the group of various chitosans, alginates, such as sodium alginate, aluminium hydroxide, sodium carboxymethyl cellulose, and sodium hydrogen carbonate. Such carriers may be used either alone or as combinations of two or more substances.
  • composition which releases at least a portion of its contents already in the mouth, contains at least one - preferably two - polymers, in the form of additives, such as carriers, fillers or binders, which have the task of keeping the drug as long as possible, for two hours minimum, in the mouth so that it forms a gel that adheres to the mucous membranes.
  • Another task of the polymers is to prolong the release of the active agent(s).
  • Such a formulation is preferably in the form of a tablet, capsule, lozenge or chewing gum, forms a gel when placed in contact with the saliva, and is most suitably formulated to be kept in the mouth, by the subject placing it under the tongue, sucking on it or chewing on it.
  • the composition of the said formulation comprises the said polymers and optional further additives.
  • the amount of polymers in this formulation is 10- 50%, preferably 15-40%, and most preferably 20-30%.
  • composition according to the present invention is formulated for release of at least a portion of its active agent(s) in the contents of the stomach. Said release is typically controlled, for example using one or more carriers.
  • Such a composition preferably contains also a filler in the form of calcium hydrogen phosphate (CaFffC ⁇ ), which has the advantage of i) not swelling in the stomach content and ii) being suitable for direct compression.
  • a filler in the form of calcium hydrogen phosphate (CaFffC ⁇ ) which has the advantage of i) not swelling in the stomach content and ii) being suitable for direct compression.
  • composition is preferably 30-70%), most suitably 40-60%).
  • such a composition preferably contains a binder selected among any known enteric polymers, preferably a methacrylate derivative, e.g. Eudragit, and most suitably Eudragit RS-PO.
  • the amount of enteric polymer in the composition is preferably 2-5%, most preferably 3-4% of the entire composition.
  • Such a composition can also contain other conventional additives, such as titanium dioxide, preferably in minor amounts of 2- 5% of the entire composition.
  • polymers as carriers, it is particularly preferred to mix the polymer(s) or the active agent(s) with 10-30%), preferably 20%> of sodium hydrogen carbonate of the weight of the polymer(s).
  • the total amount of polymers in the composition is then, generally, 10-50%, preferably 15- 40%, and most preferably 20-30% of the total weight of the composition.
  • a formulation intended to be swallowed by the subject is suitably in the form of a tablet or a capsule, particularly comprising a mixture of powder or granules. Most preferably, it is in the form of capsules comprising granules.
  • these granules contain binders preferably selected from enteric polymers, e.g. methacrylate derivatives, the solution pH of which is 6-7 and the total amount of the weight of the preparation is 2-5%, preferably 3-4%.
  • the formulation prepared according to the present invention is intended to be administered to patients (subjects) suffering from AG.
  • a long- term treatment is possible and large doses can be used, because the composition of the invention contains no substances that even in large concentrations are harmful or toxic.
  • the units or formulations are administered to a subject using a daily dose of 300 to 1500 mg of cysteine(s).
  • the units or formulations are administered using a single dose of 50 to 300 mg, between meals, such as at 3- to 6-hour intervals, preferably at around 4-hour intervals, 2-6 times a day, preferably 4-6 times a day, most suitably to an empty stomach, e.g. at least 1 hour, preferably at least 2 hours (or within 2-5 hours) after the previous meal.
  • the daily dose of the composition of the present invention is, however, administered as a single dose, prior to bedtime, to allow the active agent(s) to react while the subject is asleep.
  • the present invention also introduces a novel method of treating subjects with atrophic gastritis, by administering to the said subjects (for at least 2 months), one or more units of the composition of the present invention, with a daily dose of 300 to 1500 mg of cysteine(s).
  • a non- invasive test such as the GastroPanel® test
  • stomach- specific biomarkers such as blood biomarkers.
  • This GastroPanel® test (Biohit Oyj) determines (by ELISA) the levels of pepsinogen I (PGI), pepsinogen II (PGII), gastrin- 17 (G-17) and H. pylori antibodies (HpAb; IgG, IgA or both), and enables calculation of the PGI/II ratio in the sample.
  • the condition is typically permanent, and the patient will require follow-up tests due to an increased risk of gastric cancer.
  • These patients can reduce their risk of developing gastric and/or oesophageal cancer by taking units of the composition according to the invention.
  • Measures to reduce this risk can also include screening, e.g. using the GastroPanel® test. According to the present invention, these measures are recommended for subjects with an achlorhydric or low-acid stomach caused by atrophic gastritis resulting from H.pylori infection or an autoimmune disease (500 million subjects affected worldwide).
  • the subjects to undergo treatment with the composition of the invention are selected using a simple blood test, which optionally is processed to give a serum or plasma sample.
  • the test is carried out on a fasting sample, most suitably a fasting plasma sample.
  • the test includes a step of quantitatively measuring the biomarkers indicative for H. pylori infection or AG using the said test, these biomarkers comprising pepsinogen I (PGI), pepsinogen II (PGII), pepsinogen I/II ratio (PGI/II), gastrin- 17 (G-17) and H. pylori antibodies (HpAb).
  • biomarkers indicative for H. pylori infection or AG these biomarkers comprising pepsinogen I (PGI), pepsinogen II (PGII), pepsinogen I/II ratio (PGI/II), gastrin- 17 (G-17) and H. pylori antibodies (HpAb).
  • the H. pylori antibodies are preferably IgG or IgA antibodies, or both.
  • the combination of IgA and IgG antibodies has the advantage of increased reliability as compared to testing for one antibody only. Since patients with atrophic gastritis often suffer also from an H. pylori infection, determining whether the patient has this infection using the same bio marker test is advantageous. Nearly all H. pylori -infected individuals (>90%) exhibit H. /r /orz-specific IgG antibodies, and most (approximately 70%) of these individuals also exhibit IgA antibodies. However, approximately 7% of infected individuals are positive for IgA antibodies but negative for IgG antibodies.
  • pepsinogen I 30 ⁇ g/l for the PGI/PGII ratio 3.0, for Gastrin- 17 2 or 5 pmol/1, and for HpAb 30 EIU (enzyme immunoassay units), while the reference ranges have been selected as follows: pepsinogen I 30 - 160 ⁇ g/l, pepsinogen II 3-20 ⁇ g/l, the PGI/PGII ratio ⁇ 3.0, Gastrin- 17 2-30 pmol/1 and HpAb 0 - 30 EIU.
  • Gastrin- 17 value is particularly preferred to measure the Gastrin- 17 value from either a stimulated sample to give a Gastrin- 17S value, with a cut-off value of 5 pmol/1 (reference range of 5-30 pmol/1), or from a fasting sample to give a Gastrin-17B value, with a cut-off value of 2pmol/l (reference range of 2-10 pmol/1).
  • the normal reference values are:
  • the bio marker values indicative for AG in the corpus are: pepsinogen I or II concentration in blood sample being below the reference range, the PGI/PGII ratio being below the reference range, and gastrin- 17 concentration being above the reference range.
  • the H. pylori IgA and IgG antibodies function as markers of H. pylori infection
  • the patients with an H. pylori infection and a low G-17 value either have atrophic antral gastritis, and/or so-called antral predominant gastritis characterized by a high acid output and a high risk of peptic ulcer disease.
  • these patients should undergo gastroscopy and biopsy examinations, because of an increased risk for precancer lesions or early cancer of the antrum.
  • Such patients may also be at increased risk for gastroesophageal reflux disease (GERD) and its complications.
  • GTD gastroesophageal reflux disease
  • AG of the antrum can be confirmed or excluded by assaying the concentration of protein- stimulated G-17 in the plasma.
  • the fasting level of G-17 is low due to the absence of the G-cells and the protein stimulation cannot increase the G-17 level.
  • Gastric acid in turn inhibits the secretion of G-17, and in cases with high intra-gastric acidity alone, protein stimulation clearly raises the plasma level of G-17 (the G cell population in antrum is normal).
  • a low plasma level of G-17 with a low level of PGI enable to delineate the subjects at highest risk for gastric cancer; i.e., those with extended and severe AG in both the antrum and corpus.
  • a subject with moderate or severe AG in the antrum (low levels of G-17 and positive H. pylori IgA and IgG antibodies) has an 18-times higher risk for gastric cancer than a healthy subject.
  • a subject with moderate or severe AG in the corpus (low level of PG I and /or low PG I/II ratio and high level of G-17) has "only" a 5-times higher risk for cancer than a healthy subject. If both the corpus and antrum have moderate or severe atrophic gastritis, however, the risk of gastric cancer is increased by 90 times.
  • the described biomarker tests also identifies asymptomatic subjects who are at risk of complications due to GERD (approx. one third of GERD patients are asymptomatic).
  • GERD GERD subjects with heartburn symptoms
  • NERD non-erosive reflux disease
  • ERD erosive reflux disease
  • ERD is a serious complication, which in some cases may predispose to development into Barrett ' s oesophagus and even
  • a feature that is particularly relevant for the present invention is that, using the
  • GastroPanel® biomarker test it is also possible to specifically distinguish between subjects who suffer from H. pylori -related gastritis and subjects who suffer from only chronic AG.
  • the former usually have normal PGI, elevated PGII, elevated G-17 and elevated HpAb IgG, while the latter generally have reduced levels of PGI and PGII, a PGI/II ratio of ⁇ 3.0, a variable G-17 level and a negative result for the HpAb IgG.
  • the above described GastroPanel biomarker test reliably detects H. pylori infection and reveals atrophic gastritis and associated cancer and other risks.
  • the 13C urea breath test (UBT), stool antigen test and antibody tests alone do not detect atrophic gastritis of the corpus caused by H. pylori infection or autoimmune disease, or atrophic gastritis of the antrum caused by H. pylori infection.
  • the 13C urea breath test and stool antigen test may give up to 40% false negative results.
  • Biomarker tests are non- invasive, and thus particularly suitable for diagnosing and screening atrophic gastritis and related risks in both asymptomatic patients and patients with abdominal discomfort.
  • Example 1 Treatment of AG according to the present invention
  • GastroPanel® examination (measuring the blood concentration of pepsinogen I, pepsinogen II, the PGI/II ratio, gastrin- 17 as well as H. pylori IgG and IgA antibodies) also revealed significantly reduced levels of PGI in the said volunteers, combined with increased levels of G-17.
  • test composition of the invention
  • test units were HPMC capsules each containing lOOmg L-cysteine, mixed into a granular composition that also included Eudragit RS-PO (about 50mg), calcium hydrogen phosphate (about 40mg) and titanium dioxide (about 8mg).

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Abstract

La présente invention concerne une composition pharmaceutiquement acceptable contenant une cystéine sélectionnée parmi la L-cystéine, la D-cystéine et la N-acétylcystéine, en tant que principe actif, destinée à être utilisée dans le traitement de la gastrite atrophique, ladite cystéine étant administrée en une dose située dans la plage allant de 300 à 1 500 mg par jour pendant une période de temps d'au moins 2 mois, ou pendant 3 mois, ou même 4 mois. L'invention concerne également une méthode de traitement de sujets souffrant de gastrite atrophique, ladite méthode consistant à administrer auxdits sujets une composition selon l'invention, comprenant une cystéine en tant que principe actif, à l'aide dudit régime posologique.
PCT/FI2014/050351 2013-05-13 2014-05-12 Cystéine ou dérivé associé pour le traitement de la gastrite atrophique WO2014184435A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP14797478.6A EP2996687A4 (fr) 2013-05-13 2014-05-12 Cystéine ou dérivé associé pour le traitement de la gastrite atrophique
EA201591994A EA201591994A1 (ru) 2013-05-13 2014-05-12 Цистеин или его производное для лечения атрофического гастрита
CN201480039914.7A CN105492002A (zh) 2013-05-13 2014-05-12 用于治疗萎缩性胃炎的半胱氨酸或其衍生物
HK16111568.1A HK1223284A1 (zh) 2013-05-13 2016-10-05 用於治療萎縮性胃炎的半胱氨酸或其衍生物

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FI20135503A FI20135503L (fi) 2013-05-13 2013-05-13 Kysteiini tai sen johdannainen atrofisen gastriitin hoitamiseen
FI20135503 2013-05-13

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EP (1) EP2996687A4 (fr)
CN (1) CN105492002A (fr)
EA (1) EA201591994A1 (fr)
FI (1) FI20135503L (fr)
HK (1) HK1223284A1 (fr)
WO (1) WO2014184435A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023126574A1 (fr) * 2021-12-29 2023-07-06 Biohit Oyj Utilisation de l-cystéine pour améliorer la structure et la fonction de la muqueuse gastrique

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006103316A1 (fr) * 2005-04-01 2006-10-05 Biohit Oyj Préparation alimentaire se liant à l'acétaldéhyde présent dans la bouche et dans l'appareil digestif, et méthode d'élaboration de ladite préparation
WO2007135242A1 (fr) * 2006-05-22 2007-11-29 Biohit Oyj Composition pour produits alimentaires permettant de lier l'acétaldéhyde

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CN105492002A (zh) 2016-04-13
EP2996687A4 (fr) 2016-12-07
EP2996687A1 (fr) 2016-03-23

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