NO317930B1 - Use of parathyroid hormone, its biologically active fragments, and correlated peptides for the preparation of pharmaceutical compositions for treatment in pregnancy. - Google Patents
Use of parathyroid hormone, its biologically active fragments, and correlated peptides for the preparation of pharmaceutical compositions for treatment in pregnancy. Download PDFInfo
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- NO317930B1 NO317930B1 NO19951050A NO951050A NO317930B1 NO 317930 B1 NO317930 B1 NO 317930B1 NO 19951050 A NO19951050 A NO 19951050A NO 951050 A NO951050 A NO 951050A NO 317930 B1 NO317930 B1 NO 317930B1
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- pth
- parathyroid hormone
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- 108090000445 Parathyroid hormone Proteins 0.000 title claims description 30
- 239000000199 parathyroid hormone Substances 0.000 title claims description 27
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- 229960001319 parathyroid hormone Drugs 0.000 title claims description 26
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- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 claims description 2
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- 102000004279 Oxytocin receptors Human genes 0.000 description 1
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- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
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- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
Oppfinnelsen angår anvendelse av paratyroidhormon, dets biologisk aktive fragmenter og korrelerte peptider (PTHrP) i framstilling av farmasøytiske blandinger som er egnet til å hindre abort og for tidlig fødsel, og generelt i behandling under svangerskap. The invention relates to the use of parathyroid hormone, its biologically active fragments and correlated peptides (PTHrP) in the preparation of pharmaceutical mixtures which are suitable for preventing abortion and premature birth, and in general in treatment during pregnancy.
Bakgrunn Background
Med den generiske betegnelse paratyroidhormon eller parathyroide hormoner (vanligvis indikert ved initialene PTH etterfulgt av antall aminosyrer som karakteriserer det spesielle fragment) menes en serie proteiner eller deres fragmenter som kan finnes i naturen og er forbundet med ulike fysiologiske effekter. The generic term parathyroid hormone or parathyroid hormones (usually indicated by the initials PTH followed by the number of amino acids that characterize the particular fragment) refers to a series of proteins or their fragments that can be found in nature and are associated with various physiological effects.
Slike effekter angår primært regulering av kalsemisk homøstase, som favoriserer kalsium-absorpsjon i fordøyelsessystemet ved den indirekte mekanisme ved hydroksylering av vitamin D, som øker reabsorpsjon av kalsium i nyrekanalene og aktiverer nedbrytning av bensubstans (osteoklase). I den senere tid er det vist at PTH og PTHrP har en avslappende effekt på fordøyelsesmusklene og på det vaskulære vevet; det har blitt observert en økning av blodstrømning i korona og en positive kronotropisk effekt og en negative inotropisk effekt. Hormonet og dets fragmenter administreres biologisk, og måle-systemet som for tiden er det mest brukte i enheten USP er definert som 1/100 av mengde parathyroid hormon som kreves for å øke kalsium opptatt i 100 ml normalt hundeserum i løpet av 16-18 timer etter administrering, med 1 mg. Such effects primarily concern the regulation of calcemic homeostasis, which favors calcium absorption in the digestive system by the indirect mechanism of hydroxylation of vitamin D, which increases the reabsorption of calcium in the renal canals and activates the breakdown of bone substance (osteoclasm). Recently, it has been shown that PTH and PTHrP have a relaxing effect on the digestive muscles and on the vascular tissue; an increase of blood flow in the corona and a positive chronotropic effect and a negative inotropic effect have been observed. The hormone and its fragments are administered biologically, and the measurement system that is currently the most widely used in the unit USP is defined as 1/100 of the amount of parathyroid hormone required to increase the calcium absorbed in 100 ml of normal dog serum during 16-18 hours after administration, with 1 mg.
Noen studier som er rapportert i litteraturen indikerer en in vitro virkning av paratyroidhormon, av dets fragmenter og av det korrelerte peptid (PTHrP) på kontraktilitet av rotte-uterus. Some studies reported in the literature indicate an in vitro effect of parathyroid hormone, of its fragments and of the correlated peptide (PTHrP) on contractility of the rat uterus.
I henhold til slike studier har PTH en inhiberende virkning på kontraktiliteten av uterus indusert av oksytocin, acetylcholin og prostaglandin. According to such studies, PTH has an inhibitory effect on the contractility of the uterus induced by oxytocin, acetylcholine and prostaglandin.
Litteraturen rapporterer ikke studier som evaluerer virkningen av PTH, dets fragmenter eller av PTHrP på kontraktiliteten av humant myometrium, og dessuten kan ikke de data som er rapportert foran foreslå resultater som er oppnåelige på den humane uterus fordi de strukturelle og fysiologiske forskjeller mellom disse to vevstyper ikke tillater noen forut-sigbarhet. The literature does not report studies evaluating the effect of PTH, its fragments or of PTHrP on the contractility of human myometrium, and furthermore, the data reported above cannot suggest results obtainable on the human uterus because the structural and physiological differences between these two tissue types does not allow any predictability.
Siden rotte-uterus er formet av fiberceller som er totalt forskjellig fra de hos det menneskelige myometrium, var det i henhold til slike studier ikke mulig å forutse mulig-heten for å anvende slike produkter til å forhindre abort og for tidlig fødsel sett fra at verdiene oppnådd fra dyr ikke kan ekstrapoleres til mennesker. De glatte musklene Since the rat uterus is made up of fiber cells that are totally different from those of the human myometrium, according to such studies it was not possible to foresee the possibility of using such products to prevent abortion and premature birth from the fact that the values obtained from animals cannot be extrapolated to humans. The smooth muscles
(inkludert det menneskelige myometrium) oppviser faktisk normalt ikke raske Na<+->kanaler. Sperelakis N. et al. i "Fast Na<+>channels in smotth muscle from pregnant rat uterus" - Can. J. Pysiol. Pharmacol. (70) 491-500 (1992) har vist eksistensen av slike kanaler i rotte-uterus. (including the human myometrium) actually do not normally exhibit fast Na<+->channels. Sperelakis N. et al. in "Fast Na<+>channels in smooth muscle from pregnant rat uterus" - Can. J. Physiol. Pharmacol. (70) 491-500 (1992) have shown the existence of such channels in the rat uterus.
Konsentrasjonen av reseptorer for oksytocin på myometrium-membraner resulterte kvantitativt i tilsvarende i menneske- og guineagris-uterus men omlag dobbelt så mye som det som ble funnet i rotter [Fuchs A.R. et al. i "Oxytocin antagonist and oxytocin receptors in myometrium and decidua" - Am. J. Perinatol. (6), 205-208 (1989)]. The concentration of receptors for oxytocin on myometrial membranes resulted quantitatively similar in human and guinea pig uteri but about twice as much as that found in rats [Fuchs A.R. et al. in "Oxytocin antagonist and oxytocin receptors in myometrium and decidua" - Am. J. Perinatol. (6), 205-208 (1989)].
Lopez Bemal A. et al. i "Are leukotrienes involved in human uterine contractility?" - Br. J. Obstet. Gynaecol. (96) 568-573 (1989) har bekreftet at oksytocin ikke kontraherer den usvangre menneske-uterus men kontraherer den usvangre rotte-uterus. Lopez Bemal A. et al. in "Are leukotrienes involved in human uterine contractility?" - Bro. J. Obstet. Gynaecol. (96) 568-573 (1989) have confirmed that oxytocin does not contract the non-pregnant human uterus but does contract the non-pregnant rat uterus.
En må også betrakte den betydelige strukturelle forskjell i de to organer som er involvert, faktisk er responsen fra en prøve av rotte-uters for det meste grunnet aktiviteten av lang-strakte muskler mens responsen fra humane myometrium-bånd resulterer fra ulike muskulære komponenter. One must also consider the significant structural difference in the two organs involved, in fact the response from a sample of rat uters is mostly due to the activity of long-stretched muscles while the response from human myometrial bands results from different muscular components.
Oppførselen for de to myometrium med hensyn til histamin er velkjent, rotte-uterus i estrus reagerer på histamin med en inhibisjon som er forbundet med aktiveringen av H2-reseptorer, som illustrert av Black J.W. et al. i "Definition and Antagonism of histamine H2-receptors" - Nature (236), 385-390 (1972) mens den menneskelige uterus alltid reagerer med en kontraksjon grunnet aktivering av Hl-reseptorer [Cruz M. et al. i "Effects of histamine and serotonin on the contractility of isolated pregnant and nonpregnant human myometrium" - Gynecol. Obstet. Invest. (28), 1-4 (1989)]. The behavior of the two myometriums with respect to histamine is well known, the rat uterus in estrus responds to histamine with an inhibition associated with the activation of H2 receptors, as illustrated by Black J.W. et al. in "Definition and Antagonism of histamine H2 receptors" - Nature (236), 385-390 (1972) while the human uterus always reacts with a contraction due to activation of H1 receptors [Cruz M. et al. in "Effects of histamine and serotonin on the contractility of isolated pregnant and nonpregnant human myometrium" - Gynecol. The fruit. Invest. (28), 1-4 (1989)].
Dessuten har G. Ballejo et al.i "In vitro effects of calcium entry blockers, chlorpromazine and fenoterol upon human pregnant myometrium contractility" - Br. J. Pharmacol. (89), 515-523 (1986) vist at responsen fra myometrium kan være avhengig av dyrearten siden følsomheten overfor kalsium i den menneskelige uterus og i usvangre hunde-uterus ikke viste seg å være forskjellig [Calixto J.B. e Antonio A.: "Effects of Compound D600 (metoksyverapamil) on drug-induced-contractions of isolated dog uterine miscle" - Gen. Pharmacol. (17), 203-209 (1986)] mens i den usvangre rotte-myometrium var kraften av CaCl2til å indusere kontraksjoner i en løsning rik på K<+>og Ca<2+>omlag 30-40 ganger større enn det som er vist i deres studier på menneskelig myometrium [Calixto J.B. og Loch S: "Ketamine inhibition of calcium-induced contractions in depolarized uterus. A comprarison with other calcium antagonists" - Br. J. Pharmacol. (85), 189-195 (1985)]. Som en konklusjon kan derfor effektene som observeres på menneske-uterus ikke ekstrapoleres fra det som er oppnådd fra rotte-uterus, og effekten som registreres in vitro på menneske-uterus er heller overraskende. Moreover, G. Ballejo et al. in "In vitro effects of calcium entry blockers, chlorpromazine and fenoterol upon human pregnant myometrium contractility" - Br. J. Pharmacol. (89), 515-523 (1986) showed that the response of the myometrium may be dependent on the species of animal since the sensitivity to calcium in the human uterus and in non-pregnant dog uteri was not shown to be different [Calixto J.B. e Antonio A.: "Effects of Compound D600 (methoxyverapamil) on drug-induced-contractions of isolated dog uterine muscle" - Gen. Pharmacol. (17), 203-209 (1986)] while in the non-pregnant rat myometrium the power of CaCl2 to induce contractions in a solution rich in K<+> and Ca<2+> was about 30-40 times greater than that of shown in their studies on human myometrium [Calixto J.B. and Loch S: "Ketamine inhibition of calcium-induced contractions in depolarized uterus. A comprarison with other calcium antagonists" - Br. J. Pharmacol. (85), 189-195 (1985)]. As a conclusion, therefore, the effects observed on the human uterus cannot be extrapolated from what has been obtained from the rat uterus, and the effect recorded in vitro on the human uterus is rather surprising.
Oppfinnelsen The invention
Diagram 1 viser den registrerte stimulering av kontraksjoner indusert på menneske-myometrium med oxytocin (Ox) ved en dose på 1 IO"2 U, Diagram 1 shows the recorded stimulation of contractions induced on human myometrium with oxytocin (Ox) at a dose of 1 IO"2 U,
diagram 2 viser den inhiberende effekt (flat del) indusert av intakt humant paratyroidhormon ved en dose på 8.5-10"<*>M på menneskelig myometrium stimulert med oxytocin ved en dose på MO"2 U, diagram 2 shows the inhibitory effect (flat part) induced by intact human parathyroid hormone at a dose of 8.5-10"<*>M on human myometrium stimulated with oxytocin at a dose of MO"2 U,
diagram 3 viser typiske kontraksjoner indusert av PGF2alfa (1 mg/kg) som indikerer intensitet og varighet, diagram 3 shows typical contractions induced by PGF2alpha (1 mg/kg) indicating intensity and duration,
diagram 4 viser responsen i samme dose som i diagram 3 etter administrering av intakt humant PTH ved en dose på 4-IO"<4>mg/kg, og diagram 4 shows the response at the same dose as in diagram 3 after administration of intact human PTH at a dose of 4-10"<4>mg/kg, and
diagram 5 viser på venstre side basal-verdien av uterin-kontraktilitet og fosterets puls i en gravid kvinne; de samme parametre etter den tiende infusjon med PTH 200 U er rapportert på høyre side. diagram 5 shows on the left the basal value of uterine contractility and the fetal heart rate in a pregnant woman; the same parameters after the tenth infusion with PTH 200 U are reported on the right side.
I diagrammene indikerer punktene (°) administreringstidspunktet for den indikerte substans; W (vasking) indikerer vaskingen av preparatet. In the diagrams, the points (°) indicate the time of administration of the indicated substance; W (washing) indicates the washing of the preparation.
Den foreliggende oppfinnelsen tillater bruk av paratyroidhormon, dets aktive fragmenter eller korrelerte peptider i framstilling av farmasøytiske blandinger for å hindre abort og for tidlig fødsel, og generelt til behandling under graviditet. Av hensyn til den foreliggende oppfinnelsen er de følgende spesielt indikert: The present invention allows the use of parathyroid hormone, its active fragments or correlated peptides in the preparation of pharmaceutical compositions to prevent abortion and premature birth, and generally for treatment during pregnancy. For the purposes of the present invention, the following are particularly indicated:
PTH, PTH 1-34, PTH 1-13, PTH 38-64, PTH 67-86, PTHrP. PTH, PTH 1-34, PTH 1-13, PTH 38-64, PTH 67-86, PTHrP.
Blandingene kan betraktes for intravenøs, intramuskulær, subkutan, rektal og vaginal administrering. Typen av blandingene kan i korte trekk oppsummeres som følger: en injiserbar farmasøytisk form der den aktive bestanddel er i væskefase eller, enda bedre lyofilisert, eventuelt i nærvær av et passende stabiliseirngsmiddel (albumin, pepton, PVP osv.), en egnet bærer (i tilfelle med et lyofilisert produkt: laktose, mannitol, glycin osv.) og i en bufferblanding med evne til å sikre den mest korrekte pH mht. til dens stabilitet; en rektal farmasøytisk form representert ved en stikkpille eller fortrinnsvis en myk gelatinkapsel som inneholder den aktive bestanddel suspendert i en blanding av vannløselige additiver hovedsakelig i form av glykol og/eller propylenglykol med den nødvendige fluiditet, med tilsats av polyalkohol slik som glycerin og eventuelt et stabiliseringsmiddel (albumin, pepton, PVP osv.) og en bufferblanding nødvendig for å opprettholde pH i et område som er forenelig med PTH og/eller dets aktive fragmenter; en vaginal farmasøytisk form slik som en vaginal stikkpille eller fortrinnsvis et mykt vaginalt gelatinegg (ovule) som inneholder den aktive bestanddel suspendert i en blanding av vannløselige additiver hovedsakelig tilsvarende de som foreligger i den myke gelatinkapsel for rektal anvendelse. The compositions can be considered for intravenous, intramuscular, subcutaneous, rectal and vaginal administration. The type of mixtures can be briefly summarized as follows: an injectable pharmaceutical form in which the active ingredient is in liquid phase or, even better, lyophilized, possibly in the presence of a suitable stabilizing agent (albumin, peptone, PVP, etc.), a suitable carrier (in case with a lyophilized product: lactose, mannitol, glycine, etc.) and in a buffer mixture with the ability to ensure the most correct pH in terms of to its stability; a rectal pharmaceutical form represented by a suppository or preferably a soft gelatin capsule containing the active ingredient suspended in a mixture of water-soluble additives mainly in the form of glycol and/or propylene glycol with the required fluidity, with the addition of a polyalcohol such as glycerin and optionally a stabilizer (albumin, peptone, PVP, etc.) and a buffer mixture necessary to maintain the pH in a range compatible with PTH and/or its active fragments; a vaginal pharmaceutical form such as a vaginal suppository or preferably a soft vaginal gelatin egg (ovule) containing the active ingredient suspended in a mixture of water-soluble additives substantially similar to those present in the soft gelatin capsule for rectal use.
Kvantiteten av aktiv bestanddel kan variere mellom 100 og 1000 enheter, men er fortrinnsvis mellom 400 og 800 enheter. De følgende eksempler beskriver farmasøytiske blandinger som inneholder PTH eller dets biologisk aktive fragmenter, som kan anvendes ved injeksjon (eksempel 1-6), ved rektal administrering (eksempel 7-14) og ved vaginal administrering (eksempel 15-18). De indikerte doser viser til en blanding som kan anvendes i framstilling av 1000 ampuller, rektal-kapsler eller vaginal-kapsler. The quantity of active ingredient can vary between 100 and 1000 units, but is preferably between 400 and 800 units. The following examples describe pharmaceutical compositions containing PTH or its biologically active fragments, which can be used by injection (Examples 1-6), by rectal administration (Examples 7-14) and by vaginal administration (Examples 15-18). The indicated doses refer to a mixture that can be used in the production of 1000 ampoules, rectal capsules or vaginal capsules.
Eksempel 1 Example 1
Eksempel 2 Example 2
Eksempel 3 Example 3
Eksempel 4 Eksempel 5 Eksempel 6 Eksempel 7 Example 4 Example 5 Example 6 Example 7
Eksempel 8 Example 8
Eksempel 9 Eksempel 10 Example 9 Example 10
Eksempel 11 Example 11
Eksempel 12 Eksempel 13 Eksempel 14 Example 12 Example 13 Example 14
Eksempel 15 Example 15
Eksempel 16 Eksempel 17 Eksempel 18 Example 16 Example 17 Example 18
Eksperimentelle forsøk på in vitro motilitet av fragmenter av myometrium i gravid kvinne Experimental tests on in vitro motility of fragments of myometrium in pregnant woman
Ved bruk av in vitro fragmenter av myometrium tatt under keisersnitt i henhold til teknikken beskrevet i "IL FARMACO", Edizione Scientifica 31: s. 329-336 (1976) ble det observert en netto inhiberende effekt på kontraksjon indusert av oxytocyn, som det går fram av diagram I og 2. Using in vitro fragments of myometrium taken during caesarean section according to the technique described in "IL FARMACO", Edizione Scientifica 31: pp. 329-336 (1976), a net inhibitory effect on contraction induced by oxytocin was observed, as from diagrams I and 2.
I diagram 2 er det en netto inhiberende effekt, indikert ved det flate partiet, indusert av humant paratyroidhormon (PTH) ved en dose på 8.5 IO"<8>M, på menneske- myometrium stimulert med oxytocyn ved en dose på HO'<2>U. In diagram 2, there is a net inhibitory effect, indicated by the flat part, induced by human parathyroid hormone (PTH) at a dose of 8.5 IO"<8>M, on human myometrium stimulated with oxytocin at a dose of HO'<2 >U.
Den inhiberende effekt indusert av PTH er særlig tydelig når sammenliknet med den langvarige stimulering av kontraksjoner indusert med oxytocyn (Ox) ved en dose på HO"<2>U (diagram 1). The inhibitory effect induced by PTH is particularly evident when compared with the prolonged stimulation of contractions induced by oxytocin (Ox) at a dose of HO"<2>U (diagram 1).
Dessuten er det utført forsøk med paratyroidhormon for kontraksjoner indusert av PGF2alfa ifølge teknikken beskrevet i British Journal of Pharmacology 93: 185-191 (1988). Also, experiments with parathyroid hormone have been performed for contractions induced by PGF2alpha according to the technique described in British Journal of Pharmacology 93: 185-191 (1988).
Diagram 3 viser en typisk kontraksjon indusert av PGF2alfa (1 mg/kg) som indikerer intensitet og varighet. Diagram 3 shows a typical contraction induced by PGF2alpha (1 mg/kg) indicating intensity and duration.
Dersom en sammenlikner den samme respons ved samme dose i diagram 4 kan en se en klar inhiberende effekt både med hensyn til intensitet og varighet som et resultat av administrering av komplett humant PTH i en dose på 4- IO"4 mg/kg. If one compares the same response at the same dose in diagram 4, one can see a clear inhibitory effect both with regard to intensity and duration as a result of administration of complete human PTH in a dose of 4-10"4 mg/kg.
I diagrammene indikerer punktene (°) administreringstidspunktet for den angitte substans. Bokstaven W (vasking) indikerer vaskingen av preparatet. In the diagrams, the points (°) indicate the time of administration of the indicated substance. The letter W (washing) indicates the washing of the preparation.
Eksperimentelle kliniske effekter Experimental clinical effects
Tre gravide kvinner med symptomer på for tidlig nedkomst ble observert fra den 34. til den 36 uke under svangerskapet. Pasientene ble underlagt kardiotokografi som viste bølger som avdekket uterin-kontraksjoner. Three pregnant women with symptoms of premature labor were observed from the 34th to the 36th week of pregnancy. The patients were subjected to cardiotocography which showed waves revealing uterine contractions.
Arterietrykk, puls og hudfarge ble evaluert. Kvinnene var klart klar over kontraksjonene og smertene som var forårsaket av disse kontraksjonene. Arterial pressure, pulse and skin color were evaluated. The women were clearly aware of the contractions and the pain caused by those contractions.
Kvinnene ble administrert med 100 enheter syntetisk paratyroidhormon 1-34 (to ampuller ifølge eksempel 1 og 2) ved rask infusjon (10 minutter), fortynnet i 200 cm<1>fysiologisk løsning. The women were administered 100 units of synthetic parathyroid hormone 1-34 (two ampoules according to examples 1 and 2) by rapid infusion (10 minutes), diluted in 200 cm<1> of physiological solution.
Blodprøvene ble tatt før og etter infusjon, og serumet ble frosset og lagret ved -20°C under bestemmelsen av mineralelementene (kalsium, fosfor, magnesium, alkalisk fosfatase, paratyroidhormon, progesteron, estradiol). The blood samples were taken before and after infusion, and the serum was frozen and stored at -20°C during the determination of the mineral elements (calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone, progesterone, estradiol).
Resultatene har vist effektiviteten av paratyroidhormon på uterin-kontraktilitet, mens det ikke ble ovservert noen bivirkninger verken hos mora eller fosteret. The results have shown the effectiveness of parathyroid hormone on uterine contractility, while no side effects were observed in either the mother or the foetus.
Spesielt viste kardiotokografien at bølgene henført til uterin-kontraksjoner under overvåkingsperioden (40 minutter) forsvant; fosterets puls oppviste ingen variasjoner og forble innenfor de normale grenser (diagram 5). Pasientene indikerte den umiddelbare forsvinning av utering-kontraksjoner og smerte forårsaket av samme, særlig i den lumbar-sakrale region og rapporterte også en følelse av velvære og redusert vekt eller tyngde i underlivet/mageregionen. Arterietrykket og pulsen oppviste ingen variasjoner som var verdt å merke seg, og det ble ikke registrert noen bivirkninger relatert til infusjonen av preparatet. In particular, the cardiotocography showed that the waves attributed to uterine contractions during the monitoring period (40 minutes) disappeared; the fetal heart rate showed no variations and remained within normal limits (diagram 5). The patients indicated the immediate disappearance of bowel contractions and pain caused by the same, especially in the lumbar-sacral region and also reported a feeling of well-being and reduced weight or heaviness in the abdomen/abdominal region. Arterial pressure and pulse showed no variations worth noting, and no side effects related to the infusion of the preparation were recorded.
Claims (6)
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ITMI922331A IT1255723B (en) | 1992-10-09 | 1992-10-09 | USE OF PARATORMONE, ITS BIOLOGICALLY ACTIVE FRAGMENTS AND RELATED PEPTIDES, FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS USEFUL IN THE PREVENTION AND THERAPY OF ABORTION AND PRETERMONE BIRTH AND IN GENERAL FOR THE TREATMENT OF GESTATION |
PCT/EP1993/002755 WO1994008613A2 (en) | 1992-10-09 | 1993-10-08 | Use of parathormone, of its biologically active fragments and of related peptides for treatment of pregnancy |
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