LT4487B - Antidiuretic preparation and process for preparation thereof - Google Patents
Antidiuretic preparation and process for preparation thereof Download PDFInfo
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- LT4487B LT4487B LT98-073A LT98073A LT4487B LT 4487 B LT4487 B LT 4487B LT 98073 A LT98073 A LT 98073A LT 4487 B LT4487 B LT 4487B
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- bovipressin
- vasopressin
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- urine
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- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 230000002686 anti-diuretic effect Effects 0.000 title claims abstract description 9
- 239000003160 antidiuretic agent Substances 0.000 title claims abstract description 6
- 229940124538 antidiuretic agent Drugs 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims description 4
- 239000000243 solution Substances 0.000 claims abstract description 18
- 229960003726 vasopressin Drugs 0.000 claims abstract description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 16
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 claims abstract description 16
- 108010004977 Vasopressins Proteins 0.000 claims abstract description 15
- 102000002852 Vasopressins Human genes 0.000 claims abstract description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 14
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000007924 injection Substances 0.000 claims abstract description 7
- 239000011780 sodium chloride Substances 0.000 claims abstract description 7
- 239000013543 active substance Substances 0.000 claims abstract description 6
- 238000002347 injection Methods 0.000 claims abstract description 6
- 239000003755 preservative agent Substances 0.000 claims abstract description 6
- 230000002335 preservative effect Effects 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000008351 acetate buffer Substances 0.000 claims abstract description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 18
- 230000002485 urinary effect Effects 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 9
- 210000002700 urine Anatomy 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 7
- 229960000583 acetic acid Drugs 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 4
- 239000008215 water for injection Substances 0.000 claims description 4
- 208000004880 Polyuria Diseases 0.000 claims description 3
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 claims description 3
- 230000035619 diuresis Effects 0.000 claims description 3
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- 206010036069 Polydipsia psychogenic Diseases 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 230000001817 pituitary effect Effects 0.000 claims description 2
- 208000000231 psychogenic polydipsia Diseases 0.000 claims description 2
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- 239000002253 acid Substances 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 238000010586 diagram Methods 0.000 claims 1
- 230000001272 neurogenic effect Effects 0.000 claims 1
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- 230000000694 effects Effects 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 7
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 abstract description 6
- 238000002560 therapeutic procedure Methods 0.000 abstract description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 239000001632 sodium acetate Substances 0.000 abstract description 3
- 235000017281 sodium acetate Nutrition 0.000 abstract description 3
- 210000001883 posterior pituitary gland Anatomy 0.000 abstract 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 230000002182 neurohumoral effect Effects 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 3
- 101800000989 Oxytocin Proteins 0.000 description 3
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 3
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
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- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 3
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- 230000033228 biological regulation Effects 0.000 description 2
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- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 210000003635 pituitary gland Anatomy 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101800001144 Arg-vasopressin Proteins 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010030302 Oliguria Diseases 0.000 description 1
- 102000005320 Posterior Pituitary Hormones Human genes 0.000 description 1
- 108010070873 Posterior Pituitary Hormones Proteins 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
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- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
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- 230000011224 negative regulation of urine volume Effects 0.000 description 1
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- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
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- 206010036067 polydipsia Diseases 0.000 description 1
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- 230000008092 positive effect Effects 0.000 description 1
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Išradime pateikiama farmacinė kompozicija, naudojama ligonių gydymui, esant antidiuretinio hormono nepakankamumui, bei jos gamybos būdas.The present invention provides a pharmaceutical composition for use in the treatment of patients with antidiuretic hormone deficiency and a process for its preparation.
Šio susirgimo gydymui lietuviškų vaistų nėra, arba jie yra pasenę ir neatitinka šiuolaikinių reikalavimų. Antidiuretinio hormono nepakankamumo atveju sutrinka skysčių apykaita žmogaus organizme, per parą išsiskiria net iki 20 litrų šlapimo. Aitidiuretiniai vaistai sureguliuoja išskiriamo šlapimo tūrį.There are no Lithuanian medicines for the treatment of this disease, or they are outdated and do not meet modern requirements. In the case of anti-diuretic hormone deficiency, fluid circulation in the human body is impaired, with up to 20 liters of urine per day. Aitidiuretic drugs regulate the volume of urine excreted.
Žinomas preparatas, pasižymintis antidiuretiniu veikimu, yra pituitrinas, kurio sudėtyje yra du hipofizės užpakalinės dalies hormonai (48 % oksitocino, 39 % vazopresino) ir 13 % pašalinių priemaišų. Konservantas yra fenolis.A known preparation with antidiuretic activity is pituitrine, which contains two posterior pituitary hormones (48% oxytocin, 39% vasopressin) and 13% foreign impurities. The preservative is phenol.
Pituitrino biologinis aktyvumas - 5 VV/ml. (Žr. buv. TSRS Medicinos pramonės ministerijos patvirtintą dokumentą “Grupovoj promyšlenyj reglament Nr.7-11 -45 na proizvodstvo pituitrina dlia injekcij”, 1975 m., 2, 31, 32 psl.).Pituitrine has a biological activity of 5 UU / ml. (See document approved by the former USSR Ministry of Medical Industry, "Grupovoj promyšlenyj Regulation No 7-11 -45 na proizvodstvo pituitrina dlia injection", pp. 2, 31, 32, 1975).
Taip pat žinomas preparato gamybos būdas, kuriame veikliąją medžiagą, išskirtų iš galvijų hipofizės užpakalinės dalies ekstrakto, ištirpina vandenyje, pašalina baltymus ir konservuoja 0,3 % fenolio tirpalu. Pagamintą tirpalą filtruoja ir išplisto i 1,0 - 1,1 ml ampules (Žr. buv. TSRS Medicinos pramonės ministerijos patvirtintą dokumentą “Grupovoj promyšlenyj reglament Nr.7-11-45 na proizvodstvo pituitrina dlia injekcij”, 31-34 psl.).It is also known to prepare a formulation in which the active ingredient isolated from the bovine pituitary gland extract is dissolved in water, deprotected and preserved with a 0.3% phenol solution. The reconstituted solution is filtered and dispensed into 1.0 - 1.1 ml ampoules (See the document, "Approved by the former USSR Ministry of Medical Industry," Grupovoj promyšlenyj Regulation No 7-11-45 na proizvodstvo pituitrina dlia injectionj ", pp. 31-34). .
Žinomo preparato pituitrino trūkumai:Disadvantages of the known preparation pituitrine:
1. Mažas pagaminto ekstrakto biologinis aktyvumas 3-5 VV/mg, nes koloidinės geležies tirpalas, kuris vartojamas baltymų atskyrimui, adsorbuoja veikliąją medžiagą.1. Low bioactivity of the prepared extract in 3-5 UU / mg because the colloidal iron solution used for protein separation adsorbs the active ingredient.
2. Alt bentonito adsorbuotas vazopresinas pagal anksčiau galiojusią technologiją likdavo ir ji atskirti pavykdavo tik dalinai, atliekant eliuciją su 0,1 N vandenilio chlorido rūgštimi. Tolimesnis gryninimas buvo technologiškai neįmanomas.2. Vasopressin adsorbed on Alt Bentonite was retained by the prior art and only partially isolated by elution with 0.1 N hydrochloric acid. Further purification was technologically impossible.
3. Maža tirpalų koncentracija ir būtinybė juos Iiofilizuoti.3. Low concentration of solutions and need for lyophilization.
4. Plaunant absorbento koloidinę geležį druskos rūgšties tirpalu, hormoniniai tirpalai užsiteršia mineralinėmis medžiagomis, kurias reikia vėliau pašalinti ir koncentruoti.4. By washing the absorbent colloidal iron with hydrochloric acid solution, the hormonal solutions become contaminated with minerals which must be subsequently removed and concentrated.
5. Maža išeiga ir dideli gamybos nuostoliai, nes dėl mažo gaunamos substancijos aktyvumo (ne daugiau 5 VV/mg) reikia didinti’veikliosios medžiagos masę preparate.5. Low yields and high production losses due to the low activity of the resulting substance (no more than 5 UU / mg) to increase the weight of the active ingredient in the formulation.
Išradimo tikslas - padidinti preparato farmakoterapinį aktyvumą ir patobulinti jo gamybos būdą.The object of the invention is to increase the pharmacotherapeutic activity of the preparation and to improve the method of its preparation.
Veiklioji medžiaga - arginino vazopresinas, išskirtas iš sparčiąją chromatografija (HPLC) išgryninto galvijų hipofizės užpakalinės dalies ekstrakto, - ciklinis nanopeptidas, kurio bendra formulė ęys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2Išradimo esme yra ta, kad j preparato, sudaryto iš veikliosios medžiagos, išskirtos iš galvijų hipofizės užpakalinės dalies ekstrakto, ir konservanto, sudėti įeina tokie komponentai:The active ingredient, arginine vasopressin, isolated from bovine pituitary glandular extract purified by flash chromatography (HPLC), is a cyclic nanopeptide of the general formula ε-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH 2 in that the preparation consisting of an active substance isolated from the bovine pituitary gland extract and a preservative comprises the following components:
servuojant, filtruojant ir išpilsiant į ampules, - veikliąją medžiagą - HPLC išgrynintą vazopresiną ištirpina acetatiniame buferiniame tirpale, izotonizuoja natrio cloridu, ir tirpalą konservuoja chlorbutanolhidratu.serving, filtering and dispensing into ampoules, - the active ingredient, HPLC-purified vasopressin, is dissolved in acetate buffer, isotonic with sodium chloride, and preserved with chlorobutanol hydrate.
Išradimo esmė yra taip pat ta, kad jis skirtas necukrinio diabeto gydymui.The invention is also directed to the treatment of non-diabetes mellitus.
Antidiuretinio preparato, vadinamo Bovipresinu, gamybos būdo pavyzdys.An example of a method of making an anti-diuretic called Bovipressin.
Pirmiausia paruošiama 0,1 mol/1 acto rūgšties tirpalas.First, prepare a 0,1 mol / l acetic acid solution.
5,S ml “ledinės” acto rūgšties GOST 61-75 (atitinkančios buv. TSRS valst. standarto reikalavimus) praskiedžiama 11 vandeniu injekcijoms.5 ml of glacial acetic acid GOST 61-75 (ex-USSR standard) is diluted with 11 water for injections.
Po to sudaromas buferinis tirpalas. 836,60 mol/1 acto rūgštyje ištirpinama 2,2 g natrio acetato ir praskiedžiama injekciniu vandeniu iki 1 litro tirpalo.A buffer is then formed. Dissolve 2.2 g of sodium acetate in 836.60 mol / l acetic acid and make up to one liter with water for injection.
Gautame buferiniame tirpale tirpinama 6,8 g natrio chlorido tirpalo izotonizavimui, kad tirpalo osmotinis slėgis būtų'lygus organizmo skysčių osmotiniam slėgiui. Į taip paruoštą tirpalą sudedamas konservantas. 5 g chlorbutanolhidrato sutrinama grūstuvėje ir užpilama 300 ml buferinio acetato tirpalu. Gerai išmaišoma ir supilamas likęs tirpalo kiekis (700 ml). Maišoma 10-20 min. maišykle. Sandariai uždarytame inde paliekama 12 vai. Chlorbutanolhidratui ištirpus, patikrinamas pH, kurio vertė turi būti 3,80-3,95 ribose.The resulting buffer solution is dissolved in 6.8 g of sodium chloride solution for isotonization so that the osmotic pressure of the solution is equal to the osmotic pressure of the body fluids. Add the preservative to the solution thus prepared. Triturate 5 g of chlorobutanol hydrate in a mortar and make up to 300 ml with buffer acetate. Mix well and add the remaining solution (700 ml). Stir for 10-20 minutes. mixer. Leave in airtight container for 12 hours. After dissolving the chlorobutanol hydrate, check the pH, which should be between 3.80 and 3.95.
Po to paruoštame tirpale ištirpinama 0,01 g HPLC išvalyto vazopresino miltelių, kurių biologinis aktyvumas 450-500 VV/mg ir grynumas ne mažesnis 95 % HPLC oksitocino atžvilgiu ir gerai išmaišoma. Pagamintas tirpalas filtruojamas nuo mechaninių priemaišų per membraninius filtrus ( per membraną su porų diametru 0,22ywm). Gaunama 860 ml preparato, kuris išpilstomas po 1,1 ml į neutralaus stiklo ampules inertinių dujų aplinkoje.Then 0.01 g of HPLC-purified vasopressin powder with a biological activity of 450-500 UU / mg and a purity of at least 95% HPLC on oxytocin is dissolved in the prepared solution and mixed thoroughly. The prepared solution is filtered from mechanical impurities through membrane filters (through a membrane with a pore diameter of 0.22 µm). 860 ml of the product is obtained, which is dispensed in 1.1 ml into neutral glass ampoules in an inert gas atmosphere.
Preparatui, pasižyminčiam antidiuretiniu veikimu, pavadintam Bovipresinu injekcijoms, buvo atlikti klinikiniai tyrimai ligoniams, sergantiems necukriniu diabetu.Clinical trials have been conducted in patients with non-diabetes mellitus with an antidiuretic agent called Bovipressin for injection.
Šių tyrimų tikslas - nustatyti Bovipresino antidiuretini efektą ir toleranciją.The purpose of these studies is to determine the antidiuretic effect and tolerance of Bovipressin.
Tyrimuose dalyvavo abiejų lyčių Įvairaus amžiaus 36 ligoniai. Jie buvo suskirstyti į 4 grupes: kontrolinė - 7 ligoniai, necukrinio diabeto - 24 ligoniai, psichologinės polidipsijos - 4 ligoniai, nefrogeninio diabeto - 1 ligonis (1 diagrama).The studies involved 36 patients of both genders at various ages. They were divided into 4 groups: control - 7 patients, diabetic - 24 patients, psychological polydipsia - 4 patients, nephrogenic diabetes - 1 patient (Figure 1).
Tyrimų eigaThe course of investigations
Skysčių sulaikymo-Bovipresino mėginys atliktas, esant abejotinai necukrinio diabeto diagnozei ir skiriant 5 W Bovipresino j raumenis bei stebint kraujo plazmos ir šlapimo osmoliariškumą kas 1 vai. (iš viso 4 vai).The fluid retention-Bovipressin specimen was performed with a doubtful diagnosis of diabetes mellitus and administered 5 W Bovipressin intramuscularly and monitored for plasma and urine osmolarity every 1 hour. (4 hours total).
Skysčių saulaikymo - vazopresino mėginio rezultatai pateikti 1 lentelėje ir 1 diagramoje. Bovipresino antidiuretinis efektas stebėtas visiems ligoniams. Vienam pacientui jis buvo minimalus ir nepakankamas, kadangi šlapimo osmoliariškumas nepasiekė normos (nefrogeninio diabeto atveju). Kontrolinėje grupėje kaip ir ligoniams, sergantiems psichogenine polidipsija, šlapimo osmoliariškumas padidėjo mažiau nei 10 % (9,46 % ir 4,99 % atitinkamai). Tuo tarpu skysčių sulaikymas pastariesiems ženkliai padidino šlapimo koncentraciją (71,25 %), kas ir padėjo ekskliuduoti jiems antidiuretinio hormono nepakankamumą.Fluid retention - vasopressin sample results are shown in Table 1 and Figure 1. The antidiuretic effect of bovipressin was observed in all patients. In one patient it was minimal and inadequate, as the osmolarity of the urine was below normal (in nephrogenic diabetes). In the control group, as in patients with psychogenic polydipsia, urinary osmolarity increased by less than 10% (9.46% and 4.99%, respectively). Meanwhile, fluid retention significantly increased urinary concentrations (71.25%), which helped to exclude them from antidiuretic hormone deficiency.
Ryškiausias teigiamas Bovipresino efektas stebėtas ligoniams, sergantiems necukriniu diabetu, t. y. esant antidiuretinio hormono nepakankamumui. Šlapimo osmoliariškumas po 5 W Bovipresino injekcijos padidėjo vidutiniškai daugiau nei du kartus (63,82 %).Tokiu būdu jiems buvo patvirtinta centrinio neurohumoralinio necukrinio diabeto diagnozė.The most pronounced positive effect of bovipressin was observed in patients with diabetes mellitus, i.e. y. in the presence of antidiuretic hormone deficiency. On average, the osmolarity of urine increased more than twice (63.82%) after injection of 5 W Bovipressin, confirming the diagnosis of central neurohumoral diabetes mellitus.
Tolimesnis tyrimas buvo atliekamas skiriant Bovipresiną tik tiems ligoniams, kuriems neurohumoralinio necukrinio diabeto diagnozė nekėlė abejonės.Further study was conducted with Bovipressin only in patients whose diagnosis of neurohumoral diabetes mellitus was not in doubt.
Bovipresinas vartotas skiriant jį Į raumenis, po oda bei j veną nedidelių infuzijų pavidalu. Pastebėta, jog skiriant medikamentą Į raumenis gaunamas greitas ir trumpesnis efektas. Injekuojant po oda poveikis tęsiasi ilgiau. Į veną skirtas ligoniams po neurochirurginių operacijų ar kitais atvejais esant indikacijoms infuzoterapijai. Antidiuretinis Bovipresino efektas'buvo vertinamas pagal diurezės bei suvartojamų skysčių dinamiką bei šlapimo osmoliariškumo kitimus paros bėgyje, tiriant jj kas 3 valandas (9-12-15-18-21-24-3-6 vai.). Dozė buvo koreguojama siekiant palaikyti šlapirfio osmoliariškumą vidutinės normos ribose (600±20Q mmol/kg) vengiant medikamento perdozavimo.Bovipressin was administered by intramuscular, subcutaneous and intravenous administration as small infusions. Administration of the drug has been shown to produce a rapid and shorter effect on the muscles. With subcutaneous injection, the effects last longer. Intravenous use in patients following neurosurgical surgery or in other indications for infusion therapy. The anti-diuretic effect of bovipressin was assessed by diuresis and fluid intake dynamics as well as changes in urinary osmolarity over a period of 3 hours (9-12-15-18-21-24-3-6 hours). The dose was adjusted to maintain the osmolarity of urethral within the normal range (600 ± 20Q mmol / kg) avoiding overdose.
Pradinė dozė buvo parenkama minimali ir palaipsniui didinama priklausomai nuo ligos sunkumo laipsnio (2 lentelė). Tačiau pastebėta, jog Bovipresino veikimo efektas priklausė ne vien nuo ligos sunkumo -1, y. antidiuretinio hormono nepakankamumo laipsnio, bet ir nuo ligos trukmės bei anksčiau vartoto medikamento ir kiekvienam ligoniui buvo individualus.The starting dose was minimal and gradually increased depending on the severity of the disease (Table 2). However, the effect of bovipressin was not only dependent on the severity of the disease, -1. the degree of antidiuretic hormone deficiency, but also according to the duration of the disease and the medication used, and was individual to each patient.
Tiriant šlapimo osmoliariškumą nustatyta, jog Bovipresino poveikis sušvirkštus jį j raumenis trunka apie 3 vai., vėliau šlapimo osmoliariškumas artėja prie apatinės normos ribos ar tampa žemesnis (3 lentelė, 1 grafikas). Švirkšciant po oda, poveikis tęsiasi 4-6 vai., todėl skiriant 4 kartus paroje pasiekiamas tolygiausio veikimo rezultatas (2 grafikas). Intraveninės infuzijos metu medikamento veikimas nutrūksta jai pasibaigus, todėl tinka tais atvejais, kai būtina infuzoterapija (ligonis negali gerti, yra nesąmoningoje būsenoje ir pan.), o ją baigus būtina Bovipi tsiną toliau skirti j raumenis ar po oda.In the urinary osmolarity study, the effect of bovipressin on intramuscular injection was found to be approximately 3 hours, with subsequent urinary osmolarity approaching or lowering to the lower limit of normal (Table 3, Graph 1). With subcutaneous injection, the effect lasts for 4 to 6 hours, resulting in a more even effect at 4 times daily (schedule 2). During intravenous infusion, the drug stops working at the end of the infusion and is therefore suitable in cases where infusion therapy is required (the patient is unable to drink, is in an unconscious state, etc.) and should continue to administer Bovipine intramuscularly or subcutaneously.
išvadosconclusions
1. .Antidiuretinis preparatas Bovipresinas efektyvus esant neurohumoraliniam necukriniam diabetui, padidinantis antidiurezę ir šlapimo osmoliariškumą ne mažiau kaip du kartus.1. .Antiidiuretic agent Bovipressin is effective in neurohumoral non-diabetic diabetes, at least doubling antidiuresis and urinary osmolarity.
2. Bovipresino dozė ligoniui turi būti parenkama individualiai priklausomai nuo antidiuretinio hormono nepakankamumo laipsnio ir individualaus jautrumo medikamentui.2. The dose of bovipressin to be administered to the patient should be individualized according to the degree of anti-diuretic hormone deficiency and individual sensitivity to the medicinal product.
3. Jautrumas Bovipresinui priklauso nuo ligos trukmės ir vartoto vazopresino preparato. Ligoniams, ilgai vartojusiems sintetinio vazopresino preparatus, medikamento efektas blogesnis.3. Hypersensitivity to bovipressin depends on the duration of the disease and the vasopressin product used. Patients on long-term treatment with synthetic vasopressin have a worse drug effect.
4. Bovipresino injekcija į raumenis veikia greitai, stipriai ir trumpai, todėl labai tinka neurohumoralinio necukrinio diabeto diagnostikai atliekant skysčių sulaikymo - vazopresino mėgini.4. Intramuscular injection of bovipressin has a rapid, strong and short duration of action, making it very suitable for the diagnosis of neurohumoral diabetes mellitus in a fluid retention - vasopressin test.
5. Infuzinė medikamento forma tinka ligoniams, esantiems sunkioje ar nesąmoningoje būklėje bei po neurochirurginių operacijų ar galvos traumų, ūmai išryškėjusio ar iranzitorio necukrinio diabeto gydymui.5. The infusion formulation is suitable for the treatment of patients with severe or unconscious conditions and following neurosurgery or head trauma, acute onset or iris-diabetes.
6. Bovipresinas naudotinas tuomet, kai preparato negalima skirti intranazaliai (sloga, kataras).6. Bovipressin should be used when the product cannot be administered intranasally (runny nose, catarrh).
7. Dėl trumpo veikimo laiko medikamentą rekomenduotina skirti po oda ne rečiau kaip 3-4 kartus paroje.7. Due to the short duration of action, it is recommended that the drug be administered subcutaneously at least 3-4 times daily.
8. Bovipresino pašaliniai reiškiniai vartojant jj optimalia doze neišryškėjo.8. Adverse events of bovipressin did not occur at the optimal dose.
Pareiškiamas preparatas žymiai pranašesnis už žinomą tuo, kad padidintas farmakoterapinis preparato aktyvumas, nes gaminamas iš chromatografiškai grynos vaistinės medžiagos (substancijos), kurios biologinis aktyvumas (vazopresino grynumas ne mažesnis 95 %) ne mažiau 450 VV/mg (buvo 3-5 VV/'mg) ir oksitocino ne daugiau 0,1 %.The claimed preparation is significantly superior to the known in that it is enhanced pharmacotherapeutic activity because it is produced from chromatographically pure drug substance (substance) with a biological activity (vasopressin purity of at least 95%) of at least 450 UU / mg (was 3-5 UU / mg). mg) and oxytocin not more than 0.1%.
IŠRADIMO APIBRĖŽTISDEFINITION OF INVENTION
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LT98-073A LT4487B (en) | 1998-05-27 | 1998-05-27 | Antidiuretic preparation and process for preparation thereof |
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| LT98-073A LT4487B (en) | 1998-05-27 | 1998-05-27 | Antidiuretic preparation and process for preparation thereof |
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| LT98073A LT98073A (en) | 1998-12-28 |
| LT4487B true LT4487B (en) | 1999-04-26 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US11135265B2 (en) | 2015-01-30 | 2021-10-05 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
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1998
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11135265B2 (en) | 2015-01-30 | 2021-10-05 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
| US11207372B2 (en) | 2015-01-30 | 2021-12-28 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
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| Publication number | Publication date |
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| LT98073A (en) | 1998-12-28 |
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