NO159004B - REPORT OR ACCOUNT FOLDER. - Google Patents
REPORT OR ACCOUNT FOLDER. Download PDFInfo
- Publication number
- NO159004B NO159004B NO830663A NO830663A NO159004B NO 159004 B NO159004 B NO 159004B NO 830663 A NO830663 A NO 830663A NO 830663 A NO830663 A NO 830663A NO 159004 B NO159004 B NO 159004B
- Authority
- NO
- Norway
- Prior art keywords
- nitrofurantoin
- folder
- folds
- spine
- documents
- Prior art date
Links
- 230000000694 effects Effects 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 5
- 229960000564 nitrofurantoin Drugs 0.000 claims description 26
- NXFQHRVNIOXGAQ-YCRREMRBSA-N nitrofurantoin Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)NC(=O)C1 NXFQHRVNIOXGAQ-YCRREMRBSA-N 0.000 claims description 26
- 239000013078 crystal Substances 0.000 claims description 17
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000012047 saturated solution Substances 0.000 claims description 3
- 239000012454 non-polar solvent Substances 0.000 claims description 2
- 230000001681 protective effect Effects 0.000 abstract 2
- 239000000853 adhesive Substances 0.000 abstract 1
- 230000001070 adhesive effect Effects 0.000 abstract 1
- 238000001514 detection method Methods 0.000 abstract 1
- 206010047700 Vomiting Diseases 0.000 description 9
- 230000008673 vomiting Effects 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000002485 urinary effect Effects 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 206010025482 malaise Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000010583 slow cooling Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B42—BOOKBINDING; ALBUMS; FILES; SPECIAL PRINTED MATTER
- B42C—BOOKBINDING
- B42C9/00—Applying glue or adhesive peculiar to bookbinding
- B42C9/0056—Applying glue or adhesive peculiar to bookbinding applying tape or covers precoated with adhesive to a stack of sheets
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B42—BOOKBINDING; ALBUMS; FILES; SPECIAL PRINTED MATTER
- B42C—BOOKBINDING
- B42C11/00—Casing-in
- B42C11/02—Machines or equipment for casing-in or applying covers to pamphlets, magazines, pads, or other paper-covered booklets
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B42—BOOKBINDING; ALBUMS; FILES; SPECIAL PRINTED MATTER
- B42D—BOOKS; BOOK COVERS; LOOSE LEAVES; PRINTED MATTER CHARACTERISED BY IDENTIFICATION OR SECURITY FEATURES; PRINTED MATTER OF SPECIAL FORMAT OR STYLE NOT OTHERWISE PROVIDED FOR; DEVICES FOR USE THEREWITH AND NOT OTHERWISE PROVIDED FOR; MOVABLE-STRIP WRITING OR READING APPARATUS
- B42D1/00—Books or other bound products
- B42D1/04—Books or other bound products in which the fillings and the spine portions of the covers are secured integrally, e.g. paper-backs ("livres brochès", "Broschüren")
Landscapes
- Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Business, Economics & Management (AREA)
- Educational Administration (AREA)
- Educational Technology (AREA)
- Sheet Holders (AREA)
- Two-Way Televisions, Distribution Of Moving Picture Or The Like (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Packaging For Recording Disks (AREA)
- Silver Salt Photography Or Processing Solution Therefor (AREA)
- Calculators And Similar Devices (AREA)
- Holders For Sensitive Materials And Originals (AREA)
- Computer And Data Communications (AREA)
- Facsimile Transmission Control (AREA)
Abstract
Description
Fremgangsmåte for fremstilling av nitrofurantoin med nedsatte bivirkninger. Process for the production of nitrofurantoin with reduced side effects.
Oppfinnelsen vedrører en fremgangsmåte for fremstilling The invention relates to a method for production
av nitrofurantoin med nedsatte bivirkninger. of nitrofurantoin with reduced side effects.
I løpet av mer enn 10 år har nitrofurantoin kommet til In more than 10 years, nitrofurantoin has come into existence
å innta en ledende rolle ved behandling av infeksjoner i urinorganene. Den generelle anvendelse av dette middel medfører et minimum av bivirkninger. På tross av dette har anvendelsen av nitrofurantoin som andre generelt anvendte legemidler fremkalt bivirkninger hvis unn-gåelse ville hilses med glede av legene. Den mest besværlige bi-virkning som fremkalles av nitrofurantoin, er illebefinnende og brekninger. Disse, fremkalles hos relativt få pasienter. Forskjellige forsøk til å løse dette problem med nedsatt dosering, diettforskrifter eller entrisk dragering av tabletter inneholdende forbindelsen har ikke vært heldige. to assume a leading role in the treatment of urinary tract infections. The general use of this remedy entails a minimum of side effects. Despite this, the use of nitrofurantoin like other generally used drugs has caused side effects, the avoidance of which would be welcomed by doctors. The most troublesome side effect induced by nitrofurantoin is nausea and vomiting. These are induced in relatively few patients. Various attempts to solve this problem with reduced dosage, dietary regulations or enteric coating of tablets containing the compound have not been successful.
Et formål med oppfinnelsen er å fremstille nitrofurantoin i en slik form at det antall tilfelle da forbindelsen fremkaller illebefinnende og brekninger nedsettes sterkt uten at effekten minskes. Et ytterligere formål med oppfinnelsen er å tilveiebringe nitrofurantoin i en krystallstørrelse som er lett å tilveiebringe, og som er lett å innføre i hensiktsmessig doseringsform. Et annet formål med oppfinnelsen er å tilveiebringe i krystallisert nitrofurantoin med en viss krystallstørrelse, hvorigjennom man hovedsakelig unngår fremkallelse av det illebefinnende og de brekninger som iblant opptrer ved administrering herav. An object of the invention is to produce nitrofurantoin in such a form that the number of cases in which the compound induces malaise and vomiting is greatly reduced without the effect being reduced. A further object of the invention is to provide nitrofurantoin in a crystal size which is easy to provide, and which is easy to introduce in an appropriate dosage form. Another object of the invention is to provide crystallized nitrofurantoin with a certain crystal size, which mainly avoids inducing the malaise and the vomiting that sometimes occurs when administering it.
Oppfinnelsen vedrører altså en fremgangsmåte for fremstilling av nitrofurantoin med forbedrede egenskaper med hensyn til bivirkninger, idet fremgangsmåten er karakterisert ved at man bringer nitrofurantoinet til å utkrystallisere fra en mettet oppløsning herav i et ikke polart oppløsningsmiddel, fortrinnsvis nitrometan og utvinne krystaller med overflateareal på 120 - 1000 cm /g. Det har vist seg at nitrofurantoin fremstilt på denne måten fremkaller mindre illebefinnende og brekninger ved oral administrering uten nedsettelse av virkningen. Hvis nitrofurantoin med nevnte krystall-størrelse administreres på en pasient, oppnås effektiv konsentrasjon i urinorganene uten illebefinnende og brekninger. -De resultater som er oppnådd ved administrering peroralt i en dose av 100 mg i form av en kapsel av nitrofuranoinkrystaller ifølge oppfinnelsen er oppstillet i følgende tabell. The invention therefore relates to a method for producing nitrofurantoin with improved properties with regard to side effects, the method being characterized by causing the nitrofurantoin to crystallize from a saturated solution thereof in a non-polar solvent, preferably nitromethane, and extracting crystals with a surface area of 120 - 1000 cm/g. It has been shown that nitrofurantoin produced in this way induces less nausea and vomiting when administered orally without reduction in efficacy. If nitrofurantoin with said crystal size is administered to a patient, effective concentration is achieved in the urinary organs without nausea and vomiting. - The results obtained by administration orally in a dose of 100 mg in the form of a capsule of nitrofuranoin crystals according to the invention are listed in the following table.
Av denne tabell fremgår at nitrofurantoin med en korn-størrelse tilsvarende sikt nr. 50-400, som er en enkel måte å angi kornstørrelsen medfører effektiv konsentrasjon av legemidlet i urinorganene, mens en krystallstørrelse tilsvarende sikt 80-200 kreves med hensyn til optimal virkning. This table shows that nitrofurantoin with a grain size corresponding to sieve no. 50-400, which is a simple way of specifying the grain size, results in effective concentration of the drug in the urinary organs, while a crystal size corresponding to sieve 80-200 is required with regard to optimal effect.
Et ytterligere bevis for den nedsatte tendens til å fremkalle illebefinnende og brekninger som. oppnås med krystall-størrelsen ifølge oppfinnelsen, fåes ved administrering av doser på 10 mg/kg på hunder, hvorpå brekninger lett fremkalles. Resultatet fra disse forsøk er oppstillet i følgende tabell 2. A further proof of the reduced tendency to induce nausea and vomiting which. achieved with the crystal size according to the invention, is obtained by administering doses of 10 mg/kg to dogs, after which vomiting is easily induced. The results from these experiments are listed in the following table 2.
Av denne tabell fremgår at de større nitrofurantoin-krystallene fremkaller brekninger i mindre grad, idet kornklassen tilsvarende sikt nr. 80-200 foretrekkes for oppnåelse av maksimal konsentrasjon i urinorganene med minst mulig illebefinnende og From this table it appears that the larger nitrofurantoin crystals induce vomiting to a lesser extent, as the grain class corresponding to sieve no. 80-200 is preferred for achieving maximum concentration in the urinary organs with the least possible discomfort and
brekninger. vomiting.
Nitrofurantoin med en krystallstørrelse i henhold til foreliggende oppfinnelse kan lett fåes ved at man metter et egnet oppløsningsmiddel som nitrometan, med nitrofurantoin, hensiktsmessig ved forhøyet temperatur og lar kr,ystalliseringen finne sted spontant, hensiktsmessig under langsom avkjøling. Krystalliseringen kan hvis ønsket påskyndes ved tilsetning av podningskrystall til hensiktsmessig utbytte er oppnådd ved krystallisasjonen. Det utfelte krystall-produkt filtreres, tørkes, males ved behov og siktes for å oppnå en kornklasse med ønsket kornstørrelse. Nitrofurantoin with a crystal size according to the present invention can be easily obtained by saturating a suitable solvent such as nitromethane with nitrofurantoin, suitably at an elevated temperature and allowing the crystallization to take place spontaneously, suitably under slow cooling. The crystallization can, if desired, be accelerated by the addition of seed crystal until an appropriate yield has been achieved during the crystallization. The precipitated crystal product is filtered, dried, ground if necessary and sieved to achieve a grain class with the desired grain size.
For at administreringen av nitrofurantoin med krystall-størrelse ifølge oppfinnelsen skal lettes, innesluttes nitrofurantoinet hensiktsmessig i kapsler under anvendelse av egnet dispergeringsmiddel og drøyemiddel, som melkesukker og dekstrose for å sikre jevn for-deling av dispersjonen. Man kan også anvende andre legemiddels-former, som en tiksotrop suspensjon, hvis krystallstørrelse bibeholdes. In order to facilitate the administration of nitrofurantoin with crystal size according to the invention, the nitrofurantoin is appropriately enclosed in capsules using a suitable dispersant and thickener, such as milk sugar and dextrose to ensure even distribution of the dispersion. You can also use other pharmaceutical forms, such as a thixotropic suspension, whose crystal size is maintained.
En viktig teknisk fordel med nitrofurantoinet ifølge oppfinnelsen er at det har slike tekniske egenskaper at det er lett å overføre i terapeutisk administrasjonsformer som kapsler og An important technical advantage of the nitrofurantoin according to the invention is that it has such technical properties that it is easy to transfer into therapeutic administration forms such as capsules and
tabletter. pills.
Eksempel. Example.
Vannfri nitrofurantoin med et effektivt overflateareal tilsvarende sikt nr. 80-200 fremstilles ved inndampning av en mettet oppløsning av vannfri nitrofurantoin i nitrometan. I begynnelsen av forsøket podes den mettede, kokende oppløsning med fine nitro-furantoinkrystaller. Mens nitrometanet fordampes vokser podningene til ønsket størrelse. Volumet i destillasjonsapparatets koker holdes konstant ved kontinuerlig tilsetning av klar og varm, nesten mettet utfellingsoppløsning. Denne fremstilles fra destillatet og vannfri nitrofurantoin. Anhydrous nitrofurantoin with an effective surface area corresponding to sieve no. 80-200 is produced by evaporation of a saturated solution of anhydrous nitrofurantoin in nitromethane. At the beginning of the experiment, the saturated, boiling solution is inoculated with fine nitro-furantoin crystals. While the nitromethane evaporates, the grafts grow to the desired size. The volume in the reboiler of the still is kept constant by continuous addition of clear and hot, nearly saturated precipitation solution. This is produced from the distillate and anhydrous nitrofurantoin.
Under forsøket uttas prøver, filtreres varmt og under-søkes i mikroskopet. Når krystaller med den ønskede størrelse på-treffes filtreres oppløsningen varm, mens residuet vaskes med iso-propanol for å fjerne nitrometan og tørkes natten over i et tørke-skap ved 100°C. Det tørkede materiale siktes gjennom sikt nr. 2'0 During the experiment, samples are taken, filtered hot and examined under the microscope. When crystals of the desired size are found, the solution is filtered hot, while the residue is washed with iso-propanol to remove nitromethane and dried overnight in a drying cabinet at 100°C. The dried material is sieved through sieve No. 2'0
for å bryte opp de løse agglomerater som kunne ha dannet seg under filtreringen og tørkningen. En prøve på produktet underkastes under-søkelse i ultrafiolett lys, mens det spesifikke overflateareal beregnes på grunnlag av oppløsningshastigheten. to break up the loose agglomerates that could have formed during the filtration and drying. A sample of the product is subjected to examination in ultraviolet light, while the specific surface area is calculated on the basis of the dissolution rate.
Meget ubetydelig kjernedannelse inntrer under krystallisasjonen, slik det fremgår av den fullstendige uteblivelse av meget fint materiale, forutsatt at utgangsmaterialene er rene, om-røringen er passelig og altfor høy konsentrasjon unngås. De varianter som innvirker på krystallstørrelsen er: Very negligible nucleation occurs during crystallization, as evidenced by the complete absence of very fine material, provided that the starting materials are clean, the agitation is adequate and excessively high concentration is avoided. The variants that affect the crystal size are:
a) destillasjonshastigheter er r/kg/time a) distillation rates are r/kg/hour
b) podningens størrelse, SQ, mm b) size of graft, SQ, mm
c) podningens vekt, W, g c) the weight of the graft, W, g
d) utfyllingsoppløsningens konsentrasjon, C, nitrofurantoin i g/kg nitrometan. d) the filling solution concentration, C, nitrofurantoin in g/kg nitromethane.
Den tid som kreves for at en kubisk podning med kant-lengden S o skal vokse til en kube med kantleng ° den S 1n er: The time required for a cubic graft with edge length S o to grow into a cube with edge length ° den S 1n is:
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK089882A DK154276B (en) | 1982-03-02 | 1982-03-02 | REPORT OR ACCOUNT FOLDERS |
Publications (3)
Publication Number | Publication Date |
---|---|
NO830663L NO830663L (en) | 1983-09-05 |
NO159004B true NO159004B (en) | 1988-08-15 |
NO159004C NO159004C (en) | 1988-11-23 |
Family
ID=8098787
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO830663A NO159004C (en) | 1982-03-02 | 1983-02-25 | REPORT OR ACCOUNT FOLDER. |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP0087976B1 (en) |
JP (1) | JPS58160199A (en) |
AT (1) | ATE23293T1 (en) |
BR (1) | BR8301075A (en) |
DE (1) | DE3367351D1 (en) |
DK (1) | DK154276B (en) |
NO (1) | NO159004C (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2184981B (en) * | 1985-09-25 | 1990-07-11 | Easibind Ltd | A book and method of producing same |
DE29614124U1 (en) * | 1996-08-14 | 1996-10-02 | Paul Kieser Druckerei GmbH & Co. KG, 86356 Neusäß | Album for taking a stack of pictures |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB938048A (en) * | 1961-01-23 | 1963-09-25 | Hans Biel | |
FR1382574A (en) * | 1964-02-13 | 1964-12-18 | Imprimerie Acker | Process for the rapid assembly of check forms to constitute a check book |
FR2138389B1 (en) * | 1971-05-25 | 1973-05-25 | Gergonne Pierre | |
US3957287A (en) * | 1971-11-05 | 1976-05-18 | The Maple Press Company | Book and cover therefor |
CA991219A (en) * | 1973-04-13 | 1976-06-15 | Samuel B. Smith | Pamphlet cover |
GB2097723B (en) * | 1981-04-23 | 1985-08-07 | Gwillim Ivor Gwilym | Improved binding |
-
1982
- 1982-03-02 DK DK089882A patent/DK154276B/en unknown
-
1983
- 1983-02-25 NO NO830663A patent/NO159004C/en unknown
- 1983-03-01 DE DE8383301093T patent/DE3367351D1/en not_active Expired
- 1983-03-01 JP JP58033717A patent/JPS58160199A/en active Pending
- 1983-03-01 EP EP83301093A patent/EP0087976B1/en not_active Expired
- 1983-03-01 AT AT83301093T patent/ATE23293T1/en not_active IP Right Cessation
- 1983-03-02 BR BR8301075A patent/BR8301075A/en unknown
Also Published As
Publication number | Publication date |
---|---|
NO159004C (en) | 1988-11-23 |
JPS58160199A (en) | 1983-09-22 |
DK154276B (en) | 1988-10-31 |
EP0087976B1 (en) | 1986-11-05 |
DE3367351D1 (en) | 1986-12-11 |
DK89882A (en) | 1983-09-03 |
BR8301075A (en) | 1983-11-22 |
EP0087976A1 (en) | 1983-09-07 |
NO830663L (en) | 1983-09-05 |
ATE23293T1 (en) | 1986-11-15 |
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