INVENTION
Russian Federation Patent RU2214248

A method of inducing labor in prenatal rupture of membranes in women with full-term pregnancy with DURATION immature and mature CERVICAL

A method of inducing labor in prenatal rupture of membranes in women with full-term pregnancy with DURATION immature and mature CERVICAL

Name of the inventor: Yevtushenko probation etc. .; Ivanova TW .; Mahmuthodzhaev A.SH .; Kufarev TI
The name of the patentee: Siberian State Medical University; Yevtushenko Irina Dmitrievna; Ivanova Tatyana; Mahmuthodzhaev Alisher Shavkatovich; Kufarev Tatiana
Address for correspondence: 634050, Tomsk, 50, Moscow highway, 2, SSMU, IP Division, US Pat. dressing. N.G.Zubarevoy
Starting date of the patent: 2001.11.12

The invention relates to medicine, namely to obstetrics, and can be used for induction of labor at antenatal discharge of amniotic fluid of women with full-term gestation against the backdrop of an immature and cervical ripening. Proposed pregnant vaginally administered 20 mg of the drug "Cytotec" 1-3 times at intervals of 4 hours on a background of a simultaneous intravenous antispasmodic. The method allows to increase efficiency of treatment and reduce the side effects of the therapy.

DESCRIPTION OF THE INVENTION

The invention relates to medicine, obstetrics, and provides methods for induction of labor at antenatal discharge of amniotic fluid in pregnant women with full-term gestation against the backdrop of an immature and cervical ripening.

Known methods for inducing labor in prenatal outpouring of water, including the appointment of common drugs: oxytocin, enzaprosta, Prostin (1, 3, 5).

The closest to the proposed on the clinical effect of a method for induction of labor in pregnant women with prenatal amniorrhea by intravenous Prostin E 2 (0.75 mg Prostin E 2) (4). However, the use of this drug leads to the development of side effects in the form of tetanic uterine contractions, fetal asphyxia, nausea, vomiting, headache, dizziness, tremors, fever, leukocytosis. Moreover, its application is limited - the drug is contraindicated in patients with a history of pelvioperitonitom, bronchial asthma, glaucoma, hypertension, cardiovascular disease, epilepsy, has a high cost (300-400 rubles in Russia.).

The task to be solved by the invention is to eliminate the drawbacks of the prototype, reduced side effects, leading to more effective treatments and expanding arsenal of tools that are used for induction of labor at antenatal discharge of amniotic fluid on the background of immature and mature cervix.

This object is achieved by the fact that after the determination of conditions for holding the procedures prescribed drug therapy, and the drug is administered vaginally "Cytotec" at a dose of 20 mg 1-3 times at intervals of 4 hours on a background of the simultaneous administration of intravenous use antispasmodic.

These features are not found in the scientific, medical and patent literature, thus, the method of the invention meets the criterion of "novelty".

The set of distinctive features does not follow explicitly to those skilled in the art. Thus, the proposed facility meets the criterion of "inventive step".

Based on the clinical trials of the method induction of labor at antenatal discharge of amniotic fluid on the background of immature and cervical ripening in pregnant women with full-term gestation it proved that the drug "Cytotec" can be successfully used as a means of stimulating labor (in the form of intravaginal 20 mg of the drug every 4 hours for 12 hours at 1-3 times background spasmolytic simultaneous intravenous infusion). Thus, the method of the invention meets the criterion of "industrial applicability".

Preparation "Cytotec" itself comprises a surfactant misoprostol (misoprostol), which is a synthetic analogue of prostaglandin E 1. Manufacturer - Searle (USA). The drug comes in tablet form. Commercial name of the drug "Cytotec". It is used to prevent stomach ulcers associated with nonsteroidal anti-inflammatory drugs, in patients with an increased risk of ulcer formation and for the treatment of acute duodenal ulcer.

The process is as follows. Women with full-term gestation during prenatal discharge of amniotic fluid in the background and immature cervical ripening begin the procedure for the development of a regular labor, including intravaginal administration of the drug "Cytotec" and intravenous antispasmodic. The conditions for carrying out procedures are full term gestational age, absence of severe extragenital diseases in women, lack of uterine scar, cephalic presentation fetus, the duration of anhydrous period of no more than 10 hours. The patient with an interval of 4 hours, vaginally (in the posterior fornix) is administered 20 mg of the drug " Cytotec "(10.1 tablets), 1 to 3 times until regular contractions. Along with each administration of the drug by intravenous infusion or bolus (slow) were infused antispasmodic (eg 4 ml Halidorum, 4 ml shpy, 2 ml 2% solution platifillina).

Clinical example

Nulliparous Konorovskaya EA, 30 years old, was admitted to the obstetric clinic SMU in order "first aid". The diagnosis on admission: Pregnancy 39-40 weeks. Prenatal rupture of membranes. Diffuse enlargement of the thyroid gland II degree. VSD on hypertonic type. Age primipara. TAA (1 spontaneous miscarriage in history).

On admission he complained of light leakage of amniotic fluid for 1 hour 15 minutes. Objectively at admission revealed: the uterus corresponds to the period of full-term pregnancy. At vaginal examination the cervix is ​​rejected posterior to the wire axis of the pelvis; length 1.5 cm; softened, but non-elastic; soft outer mouth; internal os in the form of a thin, tight-elastic "ringlet"; cervical canal pass all over for 1 finger for the internal os. The bag of water is not determined. Predlezhit head pressed against the entrance to the pelvis. Location of joints and springs is difficult to determine because of the small opening. The Cape is not reachable. Deformities of the pelvis is not. Sacral capacious basin. Light leaking amniotic fluid. At CTG: BCHSS 140 per minute. The variability in the rate. Non-stress test - a jet (Conclusion: the satisfactory condition of the fetus).

After Confirmed the absence of contraindications for the use of the method the patient carried out with the use of labor induction drug "Cytotec". When a vaginally (in the posterior fornix) administered 20 mg of the drug "Cytotec" (1/10 tablets). Simultaneously intravenous infusion held spasmolytic - platifillina (2 ml), diluted in an isotonic sodium chloride solution (20 ml).

After 1 h after drug administration "Cytotec" began regular labors and after 10 hours 05 minutes live births resulted in the birth of full-term boy with a weight of 3700, an increase of 54 cm, and Apgar scores of 8-9 points. Blood loss at delivery was 170 ml. On the seventh day after the birth the woman with the child discharged home in satisfactory condition.

Use of the drug "Cytotec" in obstetrics as a means of inducing labor in prenatal discharge of amniotic fluid on the background of unripe or ripening the cervix, it became possible, by identifying us his new property, namely the inductor birth in pregnant women.

It was shown that the drug causes a cyclical contraction of the myometrium due to the effect of prostaglandin E 1 on the contractile ability of the uterus. Prostaglandin E 1 receptor binds and induces uterine system sharp increase of the action potential, which depends on the calcium mobilization. For the occurrence of cyclic generic reductions necessary links between the myometrium cells to synchronize their activities. Such a communication system is composed of bridges formed between the cells. It has been established that estrogens promote and progesterone inhibits the formation of the bridges (6, 7). In the body, prostaglandins cause luteolysis pregnant women and the elimination of progesterone unit (2) that, apparently, is the starting point onset of labor (regular contraction of the myometrium, accompanied by structural changes in the cervix).

Property preparation "Cytotec" affect the contractile ability of the myometrium with departed amniotic fluid and unripe or ripening the cervix and thus lead to the development of labor, is not described in the literature.

Justification regime. mode of application of the drug is based on the clinical observation data for the period from June 2000 to May 2001. A single dose - 20 micrograms (total - 60 g) is sufficient for gradual exposure to cervical structure and contractile ability of the myometrium to stimulate cervical ripening and induction of labor in women with full-term gestation, and prenatal outpouring of water on the background of unripe or ripening the cervix . 4 chasa interval is optimal for drug administration, since its insertion with a shorter interval may cause hypertonicity myometrium, and lengthening of the interval will result in an insufficient effect and, accordingly, rise of anhydrous period. Multiplicity of administration 1-3 times due to the need of continuing dry period not exceeding 12 hours and confirmed by clinical observations, namely the appointment of lower doses did not give a clinical effect, the use of large doses is inexpedient. The method of administration (per vaginum) to create a primary passage of the drug through the uterus and low concentrations in the general circulation in view of its adequate absorption of vaginal mucous. Additional infusions antispasmodic conduct in parallel with the introduction of the drug enhances the effect of the drug "Cytotec".

Using the preparation "Cytotec" for the purpose of induction of labor at antenatal discharge of amniotic fluid of women with full-term gestation and unripe or ripening the cervix has been made possible thanks to the results obtained in a clinical trial. The study involved two groups of women. The total number of surveyed was 60:

Group 1: control, it included 30 women with full-term gestation, and prenatal amniorrhea who underwent labor induction enzaprostom;

2nd group: the main, it includes 30 women with full-term gestation, and prenatal discharge of amniotic fluid, which was conducted with the use of labor induction drug "Cytotec".

The study was conducted on the following parameters:

1. The duration of anhydrous period

2. The degree of maturity of the cervix

3. The time interval from the administration, and prior to the regular labor

4. The duration of labor

5. Assessment of the newborn Apgar

6. Emergency cesarean section due to the inefficiency of labor induction.

All women of the main group received the drug for the purpose of labor induction "Cytotec". Last vaginally administered 20 mg every 4 hours prior to the regular labor activity (within 12 hours of dry period) 1-3 times.

The study revealed a pronounced stimulating effect of the drug is enough "Cytotec" on the contractile ability of the myometrium and indicators of "maturity" of the cervix. Getting regular labor, apparently, can be linked to the achievement of the corresponding prostaglandin concentrations in the body (Table 1).

During clinical observation showed a significant reduction in the duration of labor (Table 2) and the number of operative delivery (Table 3) in patients from the main group. No significant differences in weight and neonatal evaluation Apgar score was not observed (Table 4).

Specific examples confirming the stimulatory effects of the drug "Cytotec" on the contractile ability of the myometrium.

1) Pregnant Sh, 28 years, the history of childbirth 262. Received obstetric clinic SMU 11.04.01 45 minutes after rupture of membranes without any signs of labor. Diagnosis: Pregnancy 40 weeks. JAA. Prenatal rupture of membranes. Ripen the cervix (7 on a scale Golubeva).

After setting the diagnosis of the patient he was appointed drug "Cytotec" for the purpose of labor induction in accordance with the method proposed by the authors in the form of a combination of intravaginal administration of 20 mg of the drug to an intravenous infusion of antispasmodic. After the introduction of the 3rd dose "Cytotec" (total dose of 60 micrograms, the time from the first injection 6 hours), the patient began regular labors and after 3 hours, 10 minutes, she gave birth to a live full-term boy with a weight of 3400, and Apgar scores 7 -9 points. The birth and the postpartum period was uneventful. On the second day after birth she was discharged home with the child in a satisfactory condition.

2) Pregnant K., 35 years old, the history of childbirth 274. Received obstetric clinic SMU 15/04/01 5 hours after the discharge of amniotic fluid with no signs of labor. Diagnosis: Pregnancy 37-38 weeks. Prenatal rupture of membranes. Immature cervix. JAA. VSD on the mixed type.

After setting the diagnosis of the patient he was appointed drug "Cytotec" for the purpose of labor induction in accordance with the method proposed by the authors in the form of a combination of intravaginal administration of 20 mg of the drug "Cytotec" 4 hours with simultaneous infusion of antispasmodic. After the introduction of the first dose "Cytotec" (total dose is 20 mcg, the time from first administration of 1 hour 15 minutes), the patient began regular labors and after 2 hours 35 minutes, she gave birth to a live full-term baby girl with a weight of 2990, and the assessment scale Apgar score 8-8. The birth and the postpartum period was uneventful. On the 5th day after birth she was discharged home with the child in a satisfactory condition.

Thus, the results obtained allow us to conclude about the presence of the drug "Cytotec" the ability to have a stimulating effect on the contractile ability of the myometrium in women with full-term gestation, and prenatal amniorrhea on background immature or cervical ripening. At this dose the intravaginal administration of this impact is realized through the reduction of muscles of the uterus body, offset twitch muscle fibers to change their relative position, the circular extension (circular) cervical muscles in the sides and top of the uterus myocytes shrinking body. The introduction of this product will result in the expansion of the arsenal of tools used for induction of labor in women with full-term gestation, and prenatal amniorrhea on background immature or cervical ripening. The drug is effective commensurate studied in comparison with the means. The drug is less expensive than the known prototype (Prostin cost 300-400 rubles in Russia - 1 dose, the price of 20 tablets (1 tablet contains 200 mg - 10 doses) preparation "Cytotec" - 166 rubles, ie a single dose of 20 mg costs 0 rubles 83 kopecks).

INFORMATION SOURCES

1. Abramchenko VV active management of labor. - SPb .: "Special literature". - 1996. - 668 p.

2. Abramchenko VV Bogdashkin NG Prostaglandins and female reproductive system. - K .: "Health". - 1988. - 168 p.

3. Mashkovskii MD Drugs. - M .: Medicine. - 1988 - 2 m -. 576 p.

4. Sidorova IS, Makarov IO Oveshnikova TZ and others. The modern principles of labor with the weakness of labor // Obstetrics and Gynecology. - 2000 - 5 - S.22-26.

5. Reference Vidal. Pharmaceuticals in Russia: A Handbook. - M.: AstraFarmServis. - 1995. - S.760-762.

6. Ngai S. W ,. Chan YM, Zam SW, ZaO TT Labour characteristics and uterine activity: misoprostol compared with oxytocin in women at term with prelabour rupture of the membrans // Br. J. Obstet. Gynaecol. - 2000. - Feb. - 107: 2. - P.222-227.

7. Wing AD, Paul RH Induction of labor with misoprostol for premature rupture of membranes beyong thirty-six week's gestation // American Journal of Obstetrics and Gynecology. - V.179. - 1. - July 1998. - P.228-231.

CLAIM

The method of induction of labor in pregnant women with full-term gestation, and prenatal amniorrhea on background unripe or ripening the cervix, including a definition of the conditions for carrying out the procedures and the subsequent appointment of pharmacotherapy, wherein the pregnant vaginally administered 20 mg of the drug "Cytotec" 1-3 times at intervals of 4 hours amid simultaneous intravenous spasmolytic.

print version
Publication date 27.03.2007gg