SE200080C1 - - Google Patents
Info
- Publication number
- SE200080C1 SE200080C1 SE200080DA SE200080C1 SE 200080 C1 SE200080 C1 SE 200080C1 SE 200080D A SE200080D A SE 200080DA SE 200080 C1 SE200080 C1 SE 200080C1
- Authority
- SE
- Sweden
- Prior art keywords
- kallikrein inactivator
- derivative
- kallikrein
- inactivator
- acid
- Prior art date
Links
- 102000001399 Kallikrein Human genes 0.000 claims description 21
- 108060005987 Kallikrein Proteins 0.000 claims description 21
- 230000000937 inactivator Effects 0.000 claims description 21
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 claims description 10
- 239000002244 precipitate Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- RLBIQVVOMOPOHC-UHFFFAOYSA-N parathion-methyl Chemical compound COP(=S)(OC)OC1=CC=C([N+]([O-])=O)C=C1 RLBIQVVOMOPOHC-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- KNIUHBNRWZGIQQ-UHFFFAOYSA-N 7-diethoxyphosphinothioyloxy-4-methylchromen-2-one Chemical compound CC1=CC(=O)OC2=CC(OP(=S)(OCC)OCC)=CC=C21 KNIUHBNRWZGIQQ-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001573961 Parotis Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
Description
KLASS INTERNATIONELLSVENSK A 61 k30 h:2/04 PATENT- OCH REGISTRERINGSVERKET Ans. 1699/1963 inkom den 15/2 1963 utlagd den 1/3 196 FARBENFABRIKEN BAYER AG, LEVERKUSEN-BAYERWERK, FORBUNDSREPUBLIKEN TYSKLAND Sat att framstalla ett svirlosligt derivat av kallikrein-inaktivatorn Upplinnare: F Schultz Prioritet begeird frau den 19 februari 1962 (Forbundsrepubliken Tgskland) Det ãr kant att man kan framstalla fran aggvita fria derivat av kallikrein-inaktivatorn (KI) frau djurkortlar genom att man. omsatter losningar av sadana kortlar genom tillsats av fallningsmedel for figgvita, sasom sulfosalicylsyra och triklorattiksyra. Kallikrein-inaktivatorn utfalles salunda icke genom tillsats av dessa medel (jmfr. tyska patentskriften 1 084 433). CLASS INTERNATIONAL SWEDISH A 61 k30 h: 2/04 PATENT AND REGISTRATION AGENCY Ans. 1699/1963 was received on 15/2 1963 issued on 1/3 196 FARBENFABRIKEN BAYER AG, LEVERKUSEN-BAYERWERK, FEDERAL REPUBLIC OF GERMANY Set to produce a virulence derivative of the kallikrein inactivator It is possible to produce aggregate-free derivatives of the kallikrein inactivator (KI) from animal cards by. reactes solutions of such cards by the addition of precipitants for white matter, such as sulfosalicylic acid and trichloroacetic acid. The Kallikrein inactivator is thus not precipitated by the addition of these agents (cf. German Patent Specification 1,084,433).
Enligt uppfinningen har det nu befunnits, att man kan framstalla ett svarlosligt derivat av kallikrein-inaktivatorn genom att omsatta densamma med ,metafosforsyra i vattenhaltig losning. Det i form av en fallning erhallna derivatet avskiljes fran reaktionsblandningen. According to the invention, it has now been found that a responsive derivative of the kallikrein inactivator can be prepared by reacting it with metaphosphoric acid in aqueous solution. The derivative obtained in the form of a precipitate is separated from the reaction mixture.
Man kan harvid ocksh. ga. tillvaga pa sa satt, att man omsatter losningar av kallikrein-inaktivatorn med vattentosliga salter av metafosforsyra, varvid nagon fanning icke uppkommer, och darefter genom surgoring utskiljer det svarlosliga derivatet. F8r detta andamal lampliga salter av metafosforsyra Oro frainfor alit alkali- och ammoniumsalterna. You can harvid ocksh. ga. prepared in such a way that solutions of the kallikrein inactivator are reacted with water-soluble salts of metaphosphoric acid, whereby no formation arises, and then the acid-soluble derivative is separated by acidification. For this purpose suitable salts of metaphosphoric acid Oro frainfor alit the alkali and ammonium salts.
Fallningen i enlighet med uppfinningen genomfores ocksa i fran aggvita fria losningar av kallikrein-inaktivatorn, t. ex. i sadana, mlka dessforinnan kvantitativt befriats frail aggvita med hjalp av sulfosalicylsyra eller triklorattiksyra. Harav framgar det, att det mid de i enlighet med foreliggande uppfinning foreslagna atgarderna fake rora sig om nagon fanning av aggvita. Fastmer mOjliggores i enlighet med forfarandet enligt uppfinningen utvinning av ett aggvitefritt, svarlosligt derivat av kallikrein-inaktivatorn. The precipitate according to the invention is also carried out in aggregate free solutions of the kallikrein inactivator, e.g. in such, milk may previously be quantitatively freed from agglomerates by means of sulfosalicylic acid or trichloroacetic acid. From this it appears that the measures proposed in accordance with the present invention are false about any formation of aggvita. However, in accordance with the process of the invention, it is possible to recover an agglite-free, unresponsive derivative of the kallikrein inactivator.
Genom fallningeii i enlighet med uppfinningen ager flagon denaturering av kallikreininaktivatorn icke rum, vilket utgor ett ytterligare bevis f8r, all det i foreliggande fall joke rot sig om flagon fallning av aggvita, eftersom aggvitautfallningar i allmanhet atfoljas av denatureringar av den. utfallda aggvitan, vilket ger sig tillkanna i en forlust i den biologiska verkan for ifragavarande substans. By precipitation in accordance with the invention, flaccid denaturation of the kallikreinin activator does not take place, which constitutes further proof that all the present case is rooted in flaccid precipitation of aggvite, since aggvite precipitates are generally followed by denaturations of it. precipitated aggvitan, which manifests itself in a loss in the biological effect of the substance in question.
Vid det uppfinningsenliga forfarandet utskiljes kallikrein-inaktivatorn kvantitativt i svarlOslig form. I detta preparat innehalles he-la den biologiska aktiviteten. PA grund av den erhallna produktens svarlOslighet ar forfarandet ocksa lampligt for rening av fororenad kallikrein-inaktivator. In the process according to the invention, the kallikrein inactivator is separated quantitatively in a soluble form. This preparation contains all the biological activity. Due to the responsiveness of the product obtained, the process is also suitable for the purification of contaminated kallikrein inactivator.
Suspensionerna av fallningsprodukten i vat-ten aro icke dialyserbara, under det att kallikrein-inaktivatorn i sin losliga form tail later sig dialyseras, aven frau landningar. The suspensions of the precipitation product in the water are not dialyzable, while the kallikrein inactivator in its loose form allows itself to be dialyzed, even from landings.
Den i enlighet med forfarandet enligt foreliggande uppfinning erhallbara produkten_ visa" vid anvandning in vivo en depaverkan. Den ar joke toxisk, utpraglat vavnadsvanlig och ay denna anledning val lampad for terapeutisk anvandning, amen fOr injektioner. The product obtainable in accordance with the method of the present invention exhibits a deposition effect when used in vivo. It is joke toxic, distinctly conventional and for this reason is preferred for therapeutic use, amen to injections.
Exempel 1. 114 mg kallikrein-inaktivator (1 enhet bunden till 0,38 y substans), motsvarande 300000 KIE, lostes i 5 ml omdestillerat vat-ten och glides med 2,5 ml 10-procentig metafosforsyra. Fallningen avcentrifugerades, tvattades tre ganger med omdestillerat vatten och suspenderas i 10 ml omdestillerat vatten. Suspensionen inneholl c:a 100 % av kallikreininaktivatoraktiviteten. Example 1. 114 mg of kallikrein inactivator (1 unit bound to 0.38 μl of substance), corresponding to 300,000 KIE, were dissolved in 5 ml of redistilled water and slid with 2.5 ml of 10% metaphosphoric acid. The precipitate was centrifuged off, washed three times with redistilled water and suspended in 10 ml of redistilled water. The suspension contained about 100% of the kallikrein inactivator activity.
Exempel 2. 114 mg kallikrein-inaktivator (1 enhet bunden till 0,38 substans), motsvarande 300000 KIE, tastes i 2,5 ml omdestillerat vatten. 10-procentig metafosforsyra installdes pa pH 6 (Lyphan-papper) med hj alp av NaOH och 2,5 ml av denna Na-metafosforsyralosning inrOrdes i kallikrein-inaktivatorlosningen. El-ter tillsats av 1 ml utspadd (1:10) isattika uppstod en fanning, som avcentrifugerades. Fallningen tvattades tre ganger med omdestil- Dupl. kl. 30 h: 2/ 2— ' — lerat vatten och suspenderades darefter i 10 ml omdestillerat vatten. Suspensionen baneholl c:a 100 % av kallikrein-inaktivatoraktiviteten. Example 2. 114 mg of kallikrein inactivator (1 unit bound to 0.38 substance), corresponding to 300,000 KIE, are diluted in 2.5 ml of redistilled water. 10% metaphosphoric acid was adjusted to pH 6 (Lyphan paper) with the aid of NaOH and 2.5 ml of this Na metaphosphoric acid solution was stirred into the kallikrein inactivator solution. After the addition of 1 ml of diluted (1:10) glacial acetic acid, a mixture was formed which was centrifuged off. The fall was washed three times with redistill- Dupl. at 30 h: 2/2 - '- clay water and then suspended in 10 ml of redistilled water. The suspension orbits about 100% of the kallikrein inactivator activity.
Exempel 3. 300 mg kallikrein-inaktivator (1 enhet bunden till 0,6 y substans), motsvarande 500000 KIE, fraanstalld frau pankreas, tes i 10 ml omdestillerat vatten oeh falldes med 7,2 ml 10-procentig metafosforsyra. ningen avcentrifugerades, tvattades tre ganger med omdestillerat vatten och suspenderades i 22,5 ml aqua redest. Utbytet uppgick till 90 dvs. 1 ml air suspensionen inn.eholl 20000 KIE. Example 3. 300 mg of kallikrein inactivator (1 unit bound to 0.6 μl of substance), corresponding to 500,000 KIE, prepared from the pancreas, was taken up in 10 ml of redistilled water and precipitated with 7.2 ml of 10% metaphosphoric acid. The mixture was centrifuged off, washed three times with redistilled water and suspended in 22.5 ml of aqua redest. The exchange amounted to 90, ie. 1 ml air suspension inn.eholl 20000 KIE.
Exempel 4. 100 ml av en saltfri, vattenhaltig lOsning av kallikrein-inaktivator (1 enhet bunden till 0,42 y substans), erhallen frail parotis, innehallande 250000 KIE, falldes med 0,2 ml 10-procentig metafosforsyra. Fanning-en tvattades efter avcentrifugering tva ganger med aqua redest, varefter Lerstoden suspenderades i 20 ml oandestillerat vatten. 1 ml av suspensionen inneholl 11250 KIE, utbytet uppgick salunda till 90 %. Example 4. 100 ml of a salt-free, aqueous solution of kallikrein inactivator (1 unit bound to 0.42 μl of substance), obtained frail parotis, containing 250,000 KIE, was precipitated with 0.2 ml of 10% metaphosphoric acid. After centrifugation, the Fanning was washed twice with aqua redest, after which the Lerstoden was suspended in 20 ml of undistilled water. 1 ml of the suspension contained 11250 KIE, the yield was thus 90%.
Exempel 5. 150 ml av en saltfri, vattenhaltig .losning air kallikrein-inaktivator (1 enhet bunden till 0,3 7 substans), erhallen frail ‘lunga, innehallande 9,9 miljoner KIE, falldes 'tiled 10 ml av en 10-procentig metafosforsyra losning. Fallningen avcentrifugerades och tvattades tva ganger med omdestillerat vatten. Example 5. 150 ml of a saline, aqueous solution of air kallikrein inactivator (1 unit bound to 0.3 7 substance), obtained frail 'lung, containing 9.9 million KIE, fell' tiled 10 ml of a 10% metaphosphoric acid solution. The precipitate was centrifuged off and washed twice with redistilled water.
Darefter suspenderades aterstoden i 330 ml omdestillerat -vatten. Den harvid uppkommande suspensionen inneholl hela mangden insatt kallikrein-inaktivator. Utbytet uppgick salunda till 100 %. 1 KIE av denna suspension ar bunden till 0,22 y. The residue was then suspended in 330 ml of redistilled water. The resulting suspension contained the full amount of kallikrein inactivator used. The yield thus amounted to 100%. 1 KIE of this suspension is bound to 0.22 y.
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE200080T |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SE200080C1 true SE200080C1 (en) | 1965-01-01 |
Family
ID=41984716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE200080D SE200080C1 (en) |
Country Status (1)
| Country | Link |
|---|---|
| SE (1) | SE200080C1 (en) |
-
0
- SE SE200080D patent/SE200080C1/sv unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO147575B (en) | FLEXIBLE ELEMENT FOR USE IN OPTICAL TRANSFER | |
| CA2184718A1 (en) | Process for preparing [l]- or [d]-homoalanin-4-yl-(methyl)phosphinic acid and its salts by racemic resolution | |
| SE8204400L (en) | METHOD OF PROCEDURE FOR POROSA CELLULOSAPERLOR | |
| Mato et al. | Chemotaxis and binding of cyclic AMP in cellular slime molds | |
| SE200080C1 (en) | ||
| FR2560879A1 (en) | PROCESS FOR RECOVERING THE ANTIBIOTIC CEFTAZIDIME | |
| US12479879B2 (en) | Method for preparing disodium 5′-guanylate heptahydrate crystal | |
| MXPA96004372A (en) | Procedure for the recovery of natamic | |
| JPH09504960A (en) | Natamycin recovery method | |
| NO167098B (en) | MODULAR PROTECTION STRUCTURE FOR UNDERWATER INSTALLATIONS. | |
| CA1190243A (en) | Drug containing a n-acyl-l-aspartyl-taurine | |
| US4578483A (en) | Gibberellin amine salts | |
| Gidley et al. | Mechanisms of antibacterial formaldehyde delivery from noxythiolin and other ‘masked‐formaldehyde’compounds | |
| NL8002273A (en) | METHOD FOR EXTRACTING SPECTOMYCIN FROM AN AQUEOUS CONCENTRATE | |
| US2376848A (en) | Method of producing crystalline rennin | |
| US4043870A (en) | Process of purifying cholesterol oxidase | |
| SU503511A3 (en) | The method of obtaining kallikreintripin inhibitor | |
| EP0081831B1 (en) | Process for purifying elastase | |
| DE1143815B (en) | Process for the optical cleavage of N-acyl-DL-trypthophanes | |
| RU1436454C (en) | Method of obtaining 2-(alcoxyphenyl)ethylamines | |
| US2719149A (en) | Preparation of crystalline potassium penicillin | |
| JPS5857420B2 (en) | DL- Phenylglycinno Kogakubunkatsuhouhou | |
| US2035642A (en) | Hormone and process of obtaining the same | |
| Holland et al. | 45. Preparation of water-soluble derivatives of 2-methylnaphthalene | |
| US3080290A (en) | Recovery of alkali-metal salts of heparin free of ammonia |