GB2120098A - Antiulcer drugs comprising ikarugamycin or capsimycin - Google Patents
Antiulcer drugs comprising ikarugamycin or capsimycin Download PDFInfo
- Publication number
- GB2120098A GB2120098A GB08310454A GB8310454A GB2120098A GB 2120098 A GB2120098 A GB 2120098A GB 08310454 A GB08310454 A GB 08310454A GB 8310454 A GB8310454 A GB 8310454A GB 2120098 A GB2120098 A GB 2120098A
- Authority
- GB
- United Kingdom
- Prior art keywords
- ikarugamycin
- capsimycin
- ulcer
- antiulcer
- antiulcer drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- GHXZHWYUSAWISC-KZRBWAKNSA-N ikarugamycin Chemical compound C([C@@H]1NC(=O)/C(C1=O)=C(\O)/C=C/[C@@H]1C2)CCNC(=O)\C=C/C[C@@H]1[C@@H]1[C@H]2[C@H]2C[C@@H](C)[C@@H](CC)[C@@H]2C=C1 GHXZHWYUSAWISC-KZRBWAKNSA-N 0.000 title claims abstract description 15
- RWOVSCDGVMSPEQ-UHFFFAOYSA-N ikarugamycin Natural products CCC1C(C)CC2C3CC4C=CC(=C5/C(=O)NC(CCCNC(=O)C=C/CC4C3C6C=CC6C12)C5=O)O RWOVSCDGVMSPEQ-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 239000003699 antiulcer agent Substances 0.000 title claims abstract description 11
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000025865 Ulcer Diseases 0.000 description 12
- 231100000397 ulcer Toxicity 0.000 description 11
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 229940057948 magnesium stearate Drugs 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000767 anti-ulcer Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- 244000299906 Cucumis sativus var. sativus Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000918585 Pythium aphanidermatum Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000003716 antitrichomonal agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An antiulcer drug comprising Ikarugamycin or Capsimycin as its active ingredient is disclosed.
Description
SPECIFICATION Antiulcer drug This invention relates to a novel antiulcer drug, and more particularly, it relates to an antiulcer drug comprising Ikarugamycin orCapsimycin as its active ingredient.
The present inventors have conducted various studies to find out new pharmacological effects of known compounds and have found that Ikarugamycin and Capsimycin, both of which having similar structures with each other, exhibit an excellent antiulcer acitivity. This invention has been accomplished on the basis of such a finding.
Accordingly, an object of the invention is to provide an antiulcer drug comprising as its active ingredient
Ikarugamycin represented by the following formula (I),
orCapsimycin represented bythefollowingformula (II).
Ikarugamycin to be used in this invention is a compound which merely has been known as an antibiotic having an antitrichomonas activity and showing aweakantibacterial activity against gram positive bacteria. Ikarugamycin is an acidic compound in the form of fine needles having a molecular formula of C29H38N204, a molecular weight of 478, melting point of 252 -- 255"C, soluble in various types of organic solvents and insoluble in water. It can be easily prepared by the fermentation method dis closed,forexample, in Japanese Patent Publication No.28833/1971.
Capsimycin is a compound which merely has been known as an antibiotic effective for cucumber diseases of gray rot and damping-off Capsimycin occurs in colorless needles and is an acidic compound having a molecularformula of C30H40N206, a molecularweight of 524.64, melting point of 186"C (decomposition), soluble in chloroform and pyridine, insoluble in ether, benzene, n-hexane and water. It can be easily prepared by the fermentation method disclosed, for example, in Japanese Patent Specification
Laid-Open No.31011980.
Antiulcer activities oflkarugamycin and Capsimycin are shown hereinafter.
(1) EffectAgainstindomethacin-induced Ulcer
Six male Donryu strain rats aged 7 weeks, each weighing 180-200 g were used per group and were fasted over48hours, afterwhichthespecimentsto be tested prepared by dissolving the compound in saline containing dimethylsulfoxide by 5% was orally administered by a predetermined amount two each rat.
After 1 hour, Indomethacin was orally administered by 25 mg/kg, and after 5 hours, 2% Brilliant blue solution was intravenously injected to them, and their stomachs were extracted. The extracted stomachs were dissected to measure the major dia- meters ofthe ulcer lesions. The sum ofthe lengths (mm)wastaken as an ulcer index.
The results are shown in Table 1.
Table 1.
Ulcer Ulcer Inhibition
Dose of Specimen Index Rate (%) (mgkg) (Mean value+
Standard error)
Ikarugamycin 0.03 17.3 + 4.0 30
0.3 10.0 + 1.6 60
1.0 9.0 + 1.9 64
3.0 6.7 + 1.6 73
10.0 3.1 + 1.0 87
30.0 2.8 + 1.1 89
Control 24.7
Group 4.2
Capsimycin 25.0 14.6 + 1.8 45
50.0 2.1 + 1.3 92
Control 26.5 + 5.1
Group (2) EffectAgainstStress-induced Ulcer
(a) Ikarugamycin
Six male Donryu strain rats aged 7 weeks, each weighing 180-200 g were used per group, and to them, Ikarugamycin dissolved in saline containing dimethylsulfoxide by 5% was orally administered at a predetermined amount two each rat.
The rats were held to be fixed vertically and were immersed neck-high in a 23"C water bath for 24 hours.
Thereafter, 2% Brilliant blue solution was intravenously injected to them, and their stomachs were extracted to determine the ulcer by the same manner described in (1) above.
The results are shown in Table 2.
Table 2.
Dose of Ikaruga- Ulcer Ulcer Inhibition mycin (mean Index Rate (%) value+ (mg/kg) Standard error)
3.0 5.1 ! 2.0 77
10.0 3.4 + 2.2 85 Control Group 22.2 + 2.1
(b) Capsimycin
Eight male ddY strain mice aged 5 weeks, each weighing 23-26 g were used per group, and to them,
Capsimycin dissolved in saline containing dimethylsulfoxide by 5% was orally administered at a predetermined amount to each mouse
The mice were held to be fixed vertically and were immersed neck-high in a 23 C water bath for 8 hours.
Thereafter, 2% Brilliant blue solution was intravenously injected to them, and the stomachs were extracted to examine ulcer occurence.
The results are shown in Table 3.
Table 3.
Dose of Capeimycin Numbers of Numbers of Ulcer Inhibition (mg/kg) Ulcerated Animals / An mals
Animals / Tested 0.3 5/8 38
1 3/8 63
3 1/8 88
Control Group 8/8
As mentioned in the above, Ikarugamycin and
Capsimycin exhibitan excellent preventive effect against ulceration. Moreover, the acute toxicity levels of both compounds, which are shown below, reveal that both arethe medicaments of safety.
Ikarugamycin LD50: morethan 1,000mg/kg (oral dose, mice)
Capsimycin LD80: 600 to 700mg/kg (oral dose, mice)
The administration manner and the dose ofthe antiulcerdrug ofthe present invention are shown as follows: The administration is preferably carried out orally in the form oftablets,capsules, granules, syrups andthe likes. The amountofadministration is suitably in the range of 0.01-500mglkg daily in one to several divided oral doses for adults. The oral administration preparations can be prepared by a
conventional manner.That is, tablets, capsules,
granules and the likes can be prepared byformulating
the compound with excipientssuch as starch, lactose,
mannitol and the like; binders such as carboxymethyl
cellulose sodium, hydroxypropyl cellulose and the
like; disintegratorssuch as crystalline cellulose,
carboxymethyl cellulose calcium and the like; emol
lients such as talc, magnesium stearate and the like;
and fluidity improvers such as light silicic anhydride and the like.
The antiulcer drug of the present invention is illustrated by the following examples:
Example 1. Tablet One tablet of the following formulation was pre
pared according to a usual manner.
Ikarugamycin 100mg
D-Mannitol 150mg
Crystalline cellulose 50mg
Starch 28mg
Carboxymethyl cellulose calcium 16mg
Talc 4mg
Magnesium stearate 2mg
Total 350mg
Example 2. Capsule
Granules of the following formulation were pre
pared by a conventional manner and were charged in
a No.3 capsule.
Ikarugamycin 25mg
Crystalline cellulose 17mg Lightanhydroussilicicacid 7mg
Magnesiumstearate 1mg Example 3. Tablet One tablet of the following formulation was prepared by a conventional manner.
Capsimycin 100mg
D-Mannitol 150mg
Crystalline cellulose 50mg
Starch 28mg
Carboxymethyl cellulose calcium 16mg
Talc 4mg Magnesiumstearate 2mg
Total 350mg Example 4. Capsule
Granules of the following formulation were prepared bythe usual manner and were charged in a No.
3 capsule.
Capsimycin 25mg
Crystalline cellulose 17mg Lightanhydroussilicicacid 7mg
Magnesium stearate 1 mg
Claims (3)
1. An antiulcer drug comprising as its active ingredient Ikarugamycin represented by the following formula (I),
orCapsimycin represented bythefollowing formula (Il).
2. The antiulcer drug as claimed in Claim 1, wherein the active ingredient is formulated in combination with pharmaceutically acceptable carriers.
3. An antiulcer drug as claimed in claim 1 and substantially as described in any one of the specific examples hereinbeforesetforth.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57072960A JPS58189114A (en) | 1982-04-30 | 1982-04-30 | Antitumor agent |
| JP10006782A JPS58216119A (en) | 1982-06-11 | 1982-06-11 | Antiulcer agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB8310454D0 GB8310454D0 (en) | 1983-05-25 |
| GB2120098A true GB2120098A (en) | 1983-11-30 |
Family
ID=26414093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08310454A Withdrawn GB2120098A (en) | 1982-04-30 | 1983-04-18 | Antiulcer drugs comprising ikarugamycin or capsimycin |
Country Status (3)
| Country | Link |
|---|---|
| DE (1) | DE3315674A1 (en) |
| GB (1) | GB2120098A (en) |
| IT (1) | IT1167631B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4628833B1 (en) * | 1969-01-17 | 1971-08-21 | Fujisawa Pharmaceutical Co | Ikarugamycin antibiotic prodn by streptomyces culture |
-
1983
- 1983-04-18 GB GB08310454A patent/GB2120098A/en not_active Withdrawn
- 1983-04-28 IT IT48172/83A patent/IT1167631B/en active
- 1983-04-29 DE DE19833315674 patent/DE3315674A1/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4628833B1 (en) * | 1969-01-17 | 1971-08-21 | Fujisawa Pharmaceutical Co | Ikarugamycin antibiotic prodn by streptomyces culture |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3315674A1 (en) | 1983-11-03 |
| IT8348172A0 (en) | 1983-04-28 |
| GB8310454D0 (en) | 1983-05-25 |
| IT1167631B (en) | 1987-05-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |