WO1999064469A1 - INHIBITEURS DE FIXATION DE $i(HELICOBACTER PYLORI) - Google Patents
INHIBITEURS DE FIXATION DE $i(HELICOBACTER PYLORI) Download PDFInfo
- Publication number
- WO1999064469A1 WO1999064469A1 PCT/JP1999/002540 JP9902540W WO9964469A1 WO 1999064469 A1 WO1999064469 A1 WO 1999064469A1 JP 9902540 W JP9902540 W JP 9902540W WO 9964469 A1 WO9964469 A1 WO 9964469A1
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- WO
- WIPO (PCT)
- Prior art keywords
- gastric
- sulfate
- sulfate group
- polysaccharide
- inhibitor
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/727—Heparin; Heparan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Definitions
- the present invention is effective in inhibiting Helicobacter pylori (sometimes abbreviated as Hp) colonization inhibitor, and is effective against gastritis, gastric ulcer, and duodenal ulcer caused by infection with Helicobacter pylori.
- Hp Helicobacter pylori
- the present invention relates to an oral prophylactic or therapeutic agent which can be prevented or treated. It also relates to foods for preventing and improving gastritis, gastric ulcer and duodenal ulcer.
- Helicobacter pylori is a spiral, gram-negative bacillus with several flagella at one end, which inhabits the gastric mucosa of humans.
- the orchid was reported in 1983 by Marshall, BJ and Warren, JR of Australia, to be detected in gastric biopsies from patients with gastritis and gastric ulcer in high rates. It has been reported that it is the causative agent of gastritis, gastric ulcer, and duodenal ulcer, and is further linked to diseases such as gastric cancer.
- Helicobacter pylori infection factors such as perease produced by this bacterium, flagella for migrating mucosal mucin layer, and interleukin-8 as an inflammatory cytokine Outer membrane proteins of Cag A, which are thought to be involved in the production, vacuolation of gastric mucosal epithelial cells ⁇ Vilan ⁇ Vac A vacuolated cytotoxin, which is involved in necrosis and ulceration.
- ammonia is produced by perease, which neutralizes the gastric pH and secures a growth environment. And damage to the gastric mucosa was thought to result in gastritis, gastric ulcer, and even gastric cancer.
- Hp eradication of Helicobacter pylori is indispensable for the curative treatment of peptic ulcer, and the combination therapy of antibiotics and gastric acid secretion inhibitor is generally used as the eradication therapy.
- Hp eradication involves a combination of a proton pump inhibitor, which strongly suppresses gastric acid secretion, and multiple antibiotics. And is often used in an amount exceeding the usual dose.
- long-term administration of antibiotics may cause serious problems such as side effects and an increase in resistant bacteria.
- Oral vaccine-based immunotherapy approaches can be used to solve problems such as side effects and increase in resistant bacteria due to administration of antibiotics for the purpose of eradication.
- problems such as side effects and increase in resistant bacteria due to administration of antibiotics for the purpose of eradication.
- As a barrier little research has been done to establish new prevention and treatment methods.
- the toxicity of essential adjuvants in oral vaccines remains unresolved.
- vaccines are mainly for prevention and are not expected to be effective for patients once infected with Hp.
- fucose is not considered to be an adhesion factor, and thus does not show an effect of inhibiting Hp colonization.
- An object of the present invention is to elucidate the mechanism relating to gastric colonization of Hp involved in the development of peptic ulcer, and to provide an Hp colonization inhibitor based on the mechanism. In addition, it has no drawbacks such as side effects and increase of resistant bacteria associated with the use of antibiotics.
- An object of the present invention is to provide an effective and highly safe preventive and therapeutic agent for gastric ulcer and the like, and a food for prevention or improvement.
- the present inventors have arrived at the present invention based on new important findings regarding the establishment of Helicobacter pylori on gastric mucosa, which had not been sufficiently elucidated until now.
- urease produced by Hp plays an important role as an enzyme that converts urea in the stomach into ammonia as described above. It was thought to cause stomach ulcer, stomach cancer and so on.
- various experiments have reported that urease does not participate in the fixation of Hp to the gastric mucosa, that is, urease has no function as an adhesion factor (adhesin).
- the present inventors have unexpectedly found from the results of previous studies on Hp adhesion, and found that perease itself is involved in the adhesion of Hp to gastric mucosa.
- urease produced by HP not only functions as an enzyme that converts urea to ammonia, but also has a large function as an adhesion factor.
- urease itself binds to gastric mucosal mucin, and as a result, It has been found that proliferation is possible.
- the present inventors have obtained findings suggesting that a sulfate group is involved in a gastric mucosa mucin receptor molecule corresponding to a protease.
- a sulfate group is involved in a gastric mucosa mucin receptor molecule corresponding to a protease.
- the gist of the present invention is to provide a Helicobacter pylori fixation inhibitor containing a sulfate group-containing polysaccharide as an active ingredient other than a polysaccharide having a sulfate group and comprising 50% by mole or more of fucose, and a sulfate group.
- Helicobacter. Helicobacter. Helicobacter pylori is an inhibitor of H. pylori.
- the present invention provides a method for treating gastritis, gastric ulcer, or duodenal ulcer due to Helicobacter pylori infection containing a sulfate group-containing polysaccharide as an active ingredient other than a polysaccharide containing sulfate groups and containing 50 mol% or more of fucose.
- the present invention also relates to a prophylactic and therapeutic agent, and also to a preventive and therapeutic agent for gastritis, gastric ulcer or duodenal ulcer due to Helicobacter pylori infection, comprising a polysaccharide containing a sulfate group and a gastric acid secretion inhibitor as active ingredients.
- the present invention also provides a food for preventing or ameliorating gastritis, gastric ulcer and duodenal ulcer, to which a polysaccharide containing a sulfate group other than the polysaccharide containing a sulfate group and comprising 50% by mol or more of fucose is added. I do.
- dextran sulfate, -carrageenan, s-carrageenan, heparin, or sulfated dolane is preferable.
- FIG. 1 shows the adhesion pattern of perease to purified gastric mucin and MKN45 cells.
- FIG. 2 shows the adhesion of urease to MKN45 cells.
- FIG. 3 shows the inhibitory rates of urease adhesion of polysaccharides containing various sulfate groups.
- FIG. 4 shows the inhibitory rates of urease adhesion of polysaccharides containing various sulfate groups.
- the polysaccharide containing a sulfate group used as the Hp fixing inhibitor may be a naturally occurring one or a chemically synthesized one.
- the polysaccharide is a saccharide composed of several or more monosaccharides including an oligosaccharide, and may be any of a homopolysaccharide, a heteropolysaccharide, and a polysaccharide constituting a complex saccharide.
- the sulfate group includes 0-sulfate group and N-sulfate group (sulfoamino group), and the position of the sulfate group is not particularly limited.
- the sulfate group content of the polysaccharide containing a sulfate group used in the present invention is usually 5% or more, preferably 9 to 20%, as the sulfur content. Since the ability of Hp to inhibit gastric mucosal colonization correlates with the degree of sulfation, it is particularly preferable to use a polysaccharide having a sulfur content of about 10 to 18%.
- polysaccharides containing a sulfate group examples include, for example, naturally occurring polysaccharides containing a sulfate group, such as dextran sulfate, chondroitin sulfate, heparin, heparinoid, mannan sulfate, caronine sulfate, and carrageenan.
- Nan such as C-strength rag-nan, ⁇ -strength ruginan
- dermatan sulfate funolan, and boruilan, and the like.
- Dextran sulfate, ⁇ ⁇ -carrageenan, sugi-strike raginan, and heparin are particularly preferred. It is dextran sulfate, sucrose-carrageenan.
- Synthetic sulfate-containing polysaccharides include sulfated dolans, sulfated lactose, sulfated oligosaccharides, sulfated lentinans, sulfated schizophyllan, sulfated yeast glucan, etc. Forced drain is preferred.
- polysaccharide containing a sulfate group used in the present invention commercially available products can be used.
- chondroitin sulfate and carrageenan are used as food additives (viscosity agents), and dextran sulfate and heparin are used as raw materials for anticoagulants for subcutaneous, intramuscular, and intravenous injection.
- an extract or a purified product obtained from an animal tissue containing the sulfate group or an algae such as a red algae or a brown algae is used, or the sulfate group content is low or no. Natural polysaccharides not containing may be sulfated and used.
- Hp colonization inhibitor or anti-ulcer agent containing a sulfated polysaccharide as an active ingredient is orally administered: Since a sulfated polysaccharide has an anticoagulant effect, side effects occur when administered by injection Some drugs have oral toxicity, but oral administration is safe without such side effects. Naturally, the safety of food additives has been confirmed.
- the polysaccharide containing a sulfate group used in the present invention prevents Hp from adhering to the gastric mucosa and exerts a high eradication effect, as is clear from in vitro experiments and animal experiments described below. Therefore, a pharmaceutical composition containing a polysaccharide containing a sulfate group as an active ingredient is useful as an agent for preventing or treating gastritis, gastric ulcer or duodenal ulcer caused by colonization of Hp on the gastric mucosa.
- a food to which a polysaccharide containing a group is added can be used as a food for preventing or improving gastritis, gastric ulcer or duodenal ulcer.
- Hp adheres well to human gastric carcinoma-derived MKN-45 cells and secretes interleukin-8, an inflammatory site-inducing factor, which inhibits the ability of anti-purease hen egg antibody to inhibit Hp adhesion.
- interleukin-8 an inflammatory site-inducing factor
- this antibody efficiently inhibited the adhesion of Hp to KN cells, and also showed a significant Hp-fixation inhibitory effect in animal experiments.
- this anti-dialease hen egg antibody hardly inhibits the enzyme activity of perease. Therefore, it is suggested that urease is involved in adhesion to the gastric mucosa in addition to the previously considered action as an enzyme.
- the present inventors further revealed that the biotinylated urease specifically adheres to heparin, gastric mucin, or MKN-45 cells, and that this urease adhesion is associated with sulfate-containing polysaccharides.
- Hp colonization in the stomach was demonstrated to be dose-dependently and specifically inhibited by oral administration of sulfate-containing polysaccharides in animal experiments (see below). See experimental example).
- Hp urease produces ammonia in the stomach and damages mucous membranes, and also has a function as an adhesion factor.
- the receptor molecule of gastric mucin corresponding to peripase which is an adhesion factor of Hp, is considered to be mainly composed of sulfate groups or sulfate esters.
- a useful Hp immobilization inhibitor It is intended to provide a preventive and therapeutic agent for gastritis, gastric ulcer or duodenal ulcer, and a food for preventing or improving gastritis, gastric ulcer or duodenal ulcer.
- a polysaccharide containing a sulfate group is used as an Hp colonization inhibitor, a prophylactic agent or a therapeutic agent for gastritis, gastric ulcer, etc.
- the dosage form is arbitrary, but a form suitable for oral administration.
- a polysaccharide containing a sulfate group is used as a main ingredient, and a conventional carrier or excipient is blended with the main ingredient to form a formulation by any method and used.
- antacids sodium bicarbonate, magnesium carbonate, precipitated carbon dioxide
- Lucidum synthetic hydrotalcite, etc.
- gastric mucosal protective agents synthetic aluminum gaterate, sucralfate, copper chlorophyllin sodium, etc.
- digestive enzymes priodiastase, rivase, etc.
- the dosage of the drug of the present invention is not particularly limited, as a polysaccharide containing a sulfate group, 1 to 5 mg / kg of adult per day for prevention and 50 to 500 mg / day of adult for adult for treatment. A range of kg is preferred.
- the food In the case of foods for preventing and / or improving gastritis, gastric ulcer or duodenal ulcer, the food generally contains 0.1% or more, preferably 0.5% or more, of a sulfate-containing polysaccharide in the food.
- Hp colonization inhibitors consisting of polysaccharides containing sulfate groups, and preventive and therapeutic agents for gastritis, gastric ulcer or duodenal ulcer, can be further enhanced by the combined use of gastric acid secretion inhibitors. Can be.
- the gastric acid secretion inhibitor cimetidine, ranitidine, H 2 inhibitor formation such as famotidine, Omepurazo Ichiru, pro ton pump inhibitor one such lansoprazole may be used.
- the dosage of the gastric acid secretion inhibitor is preferably 20 to 30 mg per day for an adult.
- Formulation example 2 (tablets) of 3 tablets
- the adhesion factor of Hp is urease produced by Hp.
- this urease binds well to mucin in the gastric mucosa, as shown below.
- Porcine stomach mucin used for the urease adhesion test was prepared as follows.
- a healthy pig about 2 months old is slaughtered, the stomach is removed, and 0.1M phosphate + 0.15M NaCl + 5mM N-ethylmaleimide (NEM) is added to the phenylmethylsulfonylfluoride. (PMSF) + PBS containing lmM EDTA (pH 7.4) was added for washing.
- the stomach was incised, the mucous membrane was scraped off and suspended in the above buffer.
- the mucosal suspension was homogenized using a polyhomogenizer while cooling on ice. This was centrifuged at 15,000 xg to obtain a supernatant.
- the supernatant was centrifuged again at 25,000 xg, the supernatant was collected, dialyzed against distilled water, and freeze-dried to obtain a crude gastric mucin.
- the dried crude gastric mucin was dissolved in PBS (pH 6.8) (containing 6M guanidine hydrochloride and Protease-zeinhibiu (5 mM NEM, lmM PMS F, lmM EDTA)), and this was dissolved in a cesium chloride density gradient. (1.5 g / ml) and centrifuged at 34,000 X g for 48 hours.
- the microplate for urease adhesion test was prepared as follows.
- the perease adhesion test to the immobilized pig stomach mucin on the microplate prepared above was performed as follows.
- Purified biotinylated urease is used in adhesion media of different pH ranges (containing 0.01% twin 20 and 0.15M NaCl in 20 mM phosphate buffer.
- the pH of the adhesion medium is 2.0, 3.0, 4 0, 4.5, 5.0, 5.5, 6.0 and 6.5) to a final concentration of 7.0 g / ml.
- the prepared urease was added to each of the two wells of the microplate immobilized with mucin described above, and sensitized at 37 ° C for 60 minutes. Next, each gel was washed three times with the adhesion medium, and immediately thereafter, 10% neutral formalin (pH 7.4) was added, and the plate was fixed by leaving it at 37 ° C for 30 minutes.
- Streptavidin HRP was added to each gel to measure the amount of urease attached to the gel, and reacted at 37 ° C for 60 minutes. Then, as the substrate ortho - it was added full We two range ⁇ Min 2 HCl and H 2 0 2 reaction. The stop solution with 3N H 2 S0 4. The running plate was placed with a known amount of doublese serially diluted urease, and an unknown sample was measured from the calibration force.
- Urease adhesion test to MKN45 cells derived from human gastric cancer It has been shown that Hp adheres well to human gastric cancer-derived MKN45 cells and secretes interleukin-8 (Kabir, AMA et al., 1997, Gut 40: 49-55) (Cells are Tokai University Dispensed from the School of Medicine's Infectious Diseases Division Utilizing these cells, the adhesion ability of the biotinylated perease was examined in the same manner as in the case of the above purified gastric mucin.
- the cell suspension to obtain a monolayer culture cells were inoculated to a 2 X 10 4 cells per Uweru in 96-well micro-blanking rate, in 5% C0 2 culture equipment of 37 ° C This was performed by culturing for about 7 days.
- urease adhesion inhibition test of polysaccharides containing various sulfate groups was performed. First, a sulfate-containing polysaccharide adjusted to various concentrations was mixed with piotinylated urease, and the mixture was sensitized with shaking at 37 ° C for 60 minutes. Next, this mixture was transferred to a monolayer culture cell plate of a 96-well microplate, and sensitized again at 37 ° C. for 60 minutes while shaking the plate. Thereafter, the microplate was washed three times with the adhesion medium (pH 3.0), and the cells in each well were fixed by heating at 65 ° C for 10 minutes.
- the adhesion medium pH 3.0
- the adhesion patterns of urease to purified gastric mucin and MKN45 cells are very similar. That is, the adhesion of urease to MKN cells depends on the pH range as in the case of mucin, and MKN cells express the same receptors on the cell surface as those found in gastric mucin. (The pattern of adhesion of rarease to gastric mucin is slightly different from that of MKN45 cells in that a shoulder peak is observed even at pH 4.5, but this is the surface of MKN45 cells. This may be due to insufficient expression of urease receptor or the slightly different composition of the receptor molecule).
- Urease adhesion in the pH 3.0 region is thought to reflect the colonization of Hp in the gastric mucosa, and a substance that can inhibit perease adhesion in this pH range.
- C2 prevents Hp from colonizing the stomach, and consequently has the potential to prevent and treat gastritis and gastric ulcer.
- FIGS. 3 and 4 the urease adhesion reaction to MKN45 cells was specifically inhibited by the sulfate-containing polysaccharide.
- Figure 3 shows the average inhibition rate of urease adhesion when dextran sulfate, heparin, sugi-ragi-nan, and / c-carrage-nan were used as the sulfate-containing polysaccharides. It can be seen that the polysaccharide containing a sulfate group specifically inhibits the adhesion in a dose-dependent manner. On the other hand, dextran containing no sulfate group used as a control did not inhibit this adhesion.
- mice As an experimental animal, a hairless mouse (NS: Hr / ICR, animal breeding research institute, accession number IAR-NHI-9701) (ATCC # 72024) showing the highest sensitivity to Hp infection was used. Animal experiments were performed according to the schedule shown in Table 1 below. Specimens were dissolved in drinking water from day 2 before challenge until the time of sacrifice and administered with free drinking water. Mice consumed 4-8 ml of water per day. The challenge strain used was NSP335 strain (Cag A + and Vac A +) isolated from human clinical material, and the challenge strain was 1 x 10 9 CFU per mouse. At the end of the test administration, the mice in each group were sacrificed, the stomach was removed, and the contents were removed.
- NSP335 strain Cag A + and Vac A +
- an emulsion was prepared with a homogenizer and used as a material for Hp detection.
- the detection of Hp is carried out by inoculating the emulsion into an Hp detection medium (Poremedia Hp separation medium, Eiken Chemical Co., Ltd.), culturing at 37 ° C for 5 days by the gas pack method, and counting the number of colonies. went. Dextran sulfate, dextran, carrageenan, force doran and sulfated force doran were used as test samples.
- Hp detection medium Poremedia Hp separation medium, Eiken Chemical Co., Ltd.
- Table 21 and Table 2-2 below show the eradication effect of Hp.
- sulfate-containing polysaccharides Ichiragi ginnan, Sui ri laginan, dextran sulfate, sulfated curdlan
- Table 2-2 shows the ability to inhibit settlement.
- polysaccharides containing no sulfate group did not prevent Hp colonization, as did the untreated control group.
- Example 3 In vivo experiment (a combination of a polysaccharide containing a sulfate group and a gastric acid secretion inhibitor) As test specimens, dextran sulfate and curdlan sulfate, which showed high eradication rates in Experimental Example 2, were selected. gastric acid secretion inhibitor (H 2 inhibitors one proton pump inhibitor evening I) effects of the combination was investigated by animal experiments.
- an effective inhibitor of Helicobacter pylori on gastric mucosa can be used as a safe and effective preventive and therapeutic agent against gastritis, gastric ulcer, etc. caused by Helicobacter pylori infection, and as a food for prevention or improvement.
- the present invention is based on the discovery of factors involved in the adhesion of Helicobacter pylori to gastric mucosa and their corresponding receptors in the stomach. Unlike antibiotics, it can specifically remove Helicobacter pylori in the stomach without producing resistant bacteria unlike antibiotics, and therefore can effectively suppress gastritis, gastric ulcer, etc. . Its eradication effect is further enhanced by the combined use with a gastric acid secretion inhibitor.
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Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU37313/99A AU3731399A (en) | 1998-06-09 | 1999-05-17 | Fixation inhibitors for (helicobacter pylori) |
EP99919609A EP1002805A4 (en) | 1998-06-09 | 1999-05-17 | HELICOBACTER PYLORI FIXING INHIBITORS |
KR1020007001336A KR20010022739A (ko) | 1998-06-09 | 1999-05-17 | 헬리코박터 필로리의 정착 저해제 |
CA002300082A CA2300082A1 (en) | 1998-06-09 | 1999-05-17 | Fixation inhibitors for helicobacter pylori |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10/160531 | 1998-06-09 | ||
JP16053198 | 1998-06-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999064469A1 true WO1999064469A1 (fr) | 1999-12-16 |
Family
ID=15716992
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1999/002540 WO1999064469A1 (fr) | 1998-06-09 | 1999-05-17 | INHIBITEURS DE FIXATION DE $i(HELICOBACTER PYLORI) |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1002805A4 (ja) |
KR (1) | KR20010022739A (ja) |
AU (1) | AU3731399A (ja) |
CA (1) | CA2300082A1 (ja) |
WO (1) | WO1999064469A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100379189B1 (ko) * | 2000-12-14 | 2003-04-08 | 학교법인고려중앙학원 | 헬리코박터 파이로리에 의한 위질환 치료제용 조성물 및그 탐색방법 |
JP2006335717A (ja) * | 2005-06-03 | 2006-12-14 | Kenji Tanmachi | 組織繊維化抑制剤及び飲食品 |
WO2011109469A1 (en) * | 2010-03-03 | 2011-09-09 | Neocutis Sa | Compositions and methods for treatment of skin diseases and disorders using antimicrobial peptide sequestering compounds |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FI20011403A (fi) * | 2001-06-29 | 2002-12-30 | Carbion Oy | Menetelmä ja koostumukset vatsan sairauksien hoitoon |
EP1614357A1 (en) * | 2004-07-10 | 2006-01-11 | Cognis IP Management GmbH | Dietary supplements comprising prebiotics and fatty acid |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03169821A (ja) * | 1989-11-28 | 1991-07-23 | Kissei Pharmaceut Co Ltd | プロスタグランジンi↓2産生増強剤 |
JPH06247861A (ja) * | 1993-02-26 | 1994-09-06 | Yakult Honsha Co Ltd | 抗潰瘍剤およびその製造法 |
JPH07138166A (ja) * | 1993-09-24 | 1995-05-30 | Yakult Honsha Co Ltd | 抗潰瘍剤およびヘリコバクター・ピロリの定着阻害剤 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5116821A (en) * | 1990-11-20 | 1992-05-26 | The Procter & Gamble Company | Sulfated glyceroglucolipids as inhibitors of bacterial adherence |
SE9300139L (sv) * | 1993-01-19 | 1994-07-20 | Medicarb Ab | Framställning av ett nytt läkemedel |
-
1999
- 1999-05-17 AU AU37313/99A patent/AU3731399A/en not_active Abandoned
- 1999-05-17 CA CA002300082A patent/CA2300082A1/en not_active Abandoned
- 1999-05-17 KR KR1020007001336A patent/KR20010022739A/ko not_active Application Discontinuation
- 1999-05-17 EP EP99919609A patent/EP1002805A4/en not_active Withdrawn
- 1999-05-17 WO PCT/JP1999/002540 patent/WO1999064469A1/ja not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03169821A (ja) * | 1989-11-28 | 1991-07-23 | Kissei Pharmaceut Co Ltd | プロスタグランジンi↓2産生増強剤 |
JPH06247861A (ja) * | 1993-02-26 | 1994-09-06 | Yakult Honsha Co Ltd | 抗潰瘍剤およびその製造法 |
JPH07138166A (ja) * | 1993-09-24 | 1995-05-30 | Yakult Honsha Co Ltd | 抗潰瘍剤およびヘリコバクター・ピロリの定着阻害剤 |
Non-Patent Citations (1)
Title |
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See also references of EP1002805A4 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100379189B1 (ko) * | 2000-12-14 | 2003-04-08 | 학교법인고려중앙학원 | 헬리코박터 파이로리에 의한 위질환 치료제용 조성물 및그 탐색방법 |
JP2006335717A (ja) * | 2005-06-03 | 2006-12-14 | Kenji Tanmachi | 組織繊維化抑制剤及び飲食品 |
WO2011109469A1 (en) * | 2010-03-03 | 2011-09-09 | Neocutis Sa | Compositions and methods for treatment of skin diseases and disorders using antimicrobial peptide sequestering compounds |
US9629856B2 (en) | 2010-03-03 | 2017-04-25 | Anteis Sa | Compositions and methods for the treatment of skin diseases and disorders using antimicrobial peptide sequestering compounds |
Also Published As
Publication number | Publication date |
---|---|
KR20010022739A (ko) | 2001-03-26 |
CA2300082A1 (en) | 1999-12-16 |
EP1002805A4 (en) | 2003-01-29 |
AU3731399A (en) | 1999-12-30 |
EP1002805A1 (en) | 2000-05-24 |
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