New modes of application of controlled contraceptive administration devices

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, namely to gynaecology, and can be used for female contraception. Inventions include methods of female contraception. That is ensured by the multiple administration of a dosage form started in a day of month marked either by 'n+3', or 'n+4', or 'n+5', or 'n+6' date and taken out in a day marked by 'n' number of the next month for at least two cycles where 'n' is a date either within 1 to 25, or 1 to 24, or 1 to 23, or 1 to 22 respectively. Also, the inventions involve female contraception kits containing at least two dosage forms and patient information leaflets according to the declared modes of contraception. Besides, the inventions comprise a dosing regimen reminder system adjusted in such a manner that it allows to choose one specific date either within 1 to 25, or within 1 to 24, or within 1 to 23, or within 1 to 22 regardless of a month, as a date when the dosage form is always taken out and a date when a new dosage form shall be used either through three, or through four, or through five, or through six days thereafter respectively.

EFFECT: inventions provide convenient administration of contraceptives with maintained efficacy of contraception and its increase in certain cases.

1 tbl, 9 ex

 

The present invention relates, in General, to the field of reproductive medicine women and, in particular, female contraception. The present invention relates to new applications and devices controlled drug delivery, for example, to achieve contraception or for the treatment and/or prevention of other symptoms that are dependent on the hormonal cycle, for example, dysmenorrhoea, menorrhagia, irregular menstruation, menstrual migraine and premenstrual syndrome (PMS).

Standard practice in the field of the modes of reception of oral contraceptives is the duration of the cycle by binding to a fixed number of days and weeks. This type of regimes created due to the need to simulate the menstrual cycle in the development of contraceptives. As a result, women begin a new cycle of contraception in a fixed day of the week, such as Sunday, Monday, etc. Another result of the above approach is that it is possible to make packing for patients with the same content and form (for example, blister oral contraceptives, 21 or 28 pills)that, in turn, provides an economical means of production and helps the user to get into the habit of consistent independently of reception of contraceptive tablets.

With development the m technology and new methods of drug delivery cycle is established already not a daily intake of active ingredients, and the determining factors of the device or system in drug delivery.

Devices controlled drug delivery is widely known in the relevant field. For example, the prior art vaginal rings, implants, patches, hormonal intrauterine contraception (IUD), spray tools, etc. used to promote contraception. For example, the vaginal ring is a device controlled drug delivery for a full cycle.

In the patent EP 876815 described only commercially manufactured contraceptive vaginal ring (Nuvaring®), which is intended for the simultaneous release of steroid compounds with progestogenic activity and steroid compounds with estrogenic activity.

Ring Nuvaring contains an 11.7 mg etonogestrel (released with speed 0,120 mg per 24 hours), 2.7 mg of ethinyl-estradiol (allocated with the speed of 0.015 mg per 24 hours) and ethylenevinylacetate copolymer.

In accordance with the current mode of application of this vaginal ring it is administered for 21 days and then remove to a one-week (7-day) period for the passage of vaginal bleeding. After a week, the noise for vaginal bleeding, vagina impose new ring to provide contraception for the next female cycle or is eklov.

The disadvantage is that it requires women time to remember many moments. When applying each ring woman must remember to retrieve the ring, when are 21 days from the date of introduction, and then remember the introduction of the new ring, when is 7 days. Data key points that should be remembered every time they fall on different dates. For example, if a woman took the ring 1 January, the new ring should be entered on January 8 and eject again on January 29. Then the new ring will need to enter the 5 of February, and already this ring will have to be retrieved February 26, etc. etc. the Obvious difficulty of tracking these dates. As a result, some women forget to timely introduce and/or remove the ring, which leads to unplanned pregnancies.

Even though there are devices that help women to remember the introduction and removal of contraceptive (see, for example, patent EP 1257244), it would be the existence of the regime, which saves the contraceptive effect, and which also automatically reminds the woman of key dates and, thereby, exclude for women risks of forgetting about the need to remove the ring (or other dosage form) or enter a new ring (or other dosage form) and conception.

Thus, in accordance with anastasimatarion offers new modes of use of contraceptive dosage forms (and use of dosage forms for the treatment and/or prevention of other symptoms dependent hormonal cycle), resulting in a more accurate compliance, while maintaining the effectiveness of the contraceptive. This more accurate compliance is ensured by the functional combination of at least two dosage forms, defined in the present description for at least two cycles defined in the present description. Compliance can be achieved by using at least the second dosage forms. Without the use of any of at least the second dosage form would be required to verify compliance. Therefore, to achieve the effect of more closely match the requirements, a necessary condition is a functional combination of at least two dosage forms.

New modes in accordance with the present invention additionally lead to the fact that women will have to deal only with 12 periods in a year instead of thirteen when standard mode 21/7.

Device controlled delivery of drugs do not impose restrictive conditions, providing a fixed cycle length. The present invention takes advantage of this new opportunity by ensuring modes, which are not subject to the same cycles of fixed duration, but allow bending the duration of the cycle. The present invention has the important advantage that helps the user in acquiring skills, since it allows the introduction and extraction of the dosage form used in the mode in accordance with the present invention, at a fixed date. Therefore, the invention provides a mode of use of contraceptive cycles of injection of hormones during these certain times of cycles, the cycles are altered in order to match the number of days in the calendar month which begins the cycle.

Both of the term "month" and "calendar month" means, for the purposes of this application, any month, January, February, March, April, may, June, July, August, September, October, November or December.

The term "number" means, for the purposes of this application, any current day of the month. For example, January has 31 number. January 1, January 2, January 3, etc. etc. February contains 28 or 29; March has 31; April has 30 numbers, etc.

The term "cycle" means, for the purposes of this application, the duration of the number of days in the month that starts the cycle. In the continuation of the cycle there is a phase (or period, or interval) the introduction of the hormone and phase without hormone (or period, or interval). For example, a loop that begins in January, sost is it 31 days; cycle, which begins in February, consists of 28 or 29 days, depending on whether the common year or a leap; a cycle that begins in March has 31 days; cycle, which begins in April, consists of 30 days, etc. etc. in Addition, the cycle in accordance with the present invention represents a partial sequence of events, during which the levels of hormones in a woman's body rise and fall due to the application of the dosage form. To complete the sequence of events during which hormone levels rise, fall, rise again and again fall, the woman must complete at least two cycles of application of the dosage form.

The term "start application" means, for the purposes of this application, the imposition or introduction, or any other kind of contraceptive use or pharmaceutical preparation. For example, patches impose, and ring type.

The term "extract" means, for the purposes of this application, the extraction or separation, or any other type of extraction contraceptive or pharmaceutical dosage forms. For example, remove vaginal ring, and the patch off.

The term "dosage form" means, for the purposes of this application, device, drug delivery controlled release, for example, vaginal to LCO or patch.

The patch (transdermal system) may be, for the purposes of this application, any (contraceptive) plaster of any type, such as matrix type, reservoir type patch with several layers of tape, in which the drug is present in the adhesive until the patch that can be applied, contains enough active ingredients to at least one cycle of contraception.

The only contraceptive patch, existing on the market at the present time, is Evra®. However, the patch Evra® contains the active ingredients in quantities sufficient only for one week of contraception, i.e. not on the whole cycle, as defined in this application.

The vaginal ring may be, for the purposes of the present invention, any (contraceptive) vaginal ring, for example, Nuvaring® or such vaginal rings, which are described in the publications and patents WO 2004/103336, PCT/EP05/051189, US 4,292,965, WO 97/02015, EP 887074.

Dosage form suitable for the present invention may contain estrogen, progestogen, or a combination of both. If desired, the dosage form may also contain other active ingredients such as antimicrobial agents, folic acid, vitamins, etc.

The progestogen may be, for the purposes of the present invention, any suitable progestogen, such as desogestrel, etonogestrel is, levonorgestrel, norgestimate, norelgestromin, gestodene, nomegestrol acetate, dienoguesta, drospirenone, or any other steroid or non-steroidal compound with progestogenic activity.

Estrogenic compound may be, for the purposes of this connection, any suitable estrogen (or its salt, or a complex ester), such as estradiol, estriol, mestranol, and ethinyl-estradiol or any other steroid or non-steroidal estrogen with estrogen activity.

In a specific embodiment, the present invention progestogen is etonogestrel. In another embodiment, the progestogen is nomegestrol acetate.

In one embodiment, the present invention estrogen is ethinyl-estradiol. In another embodiment, the estrogen is estradiol or a complex ester or its salt, for example, estradiol hemihydrate.

In a specific embodiment, the progestogen is etonogestrel, and estrogen is ethinyl-estradiol or its salt, or a complex ester.

In another specific embodiment, the progestogen is nomegestrol acetate, and the estrogen is estradiol or its salt, or a complex ester.

In a specific embodiment, the progestogen is economist Elam, and the estrogen is estradiol or its salt, or a complex ester.

In another specific embodiment, the progestogen is nomegestrol acetate, and estrogen is ethinyl-estradiol.

For the purposes of the present invention, both the terms "non-hormonal phase" and "hormone-free phase" means the phase (or period or interval during the cycle in which the hormones are not entered.

For the purposes of the present invention, the term "hormonal phase" means the phase (or period or interval during the cycle in which the injected hormones.

Vaginal ring used in the present invention may contain one or more compartments. Each compartment may contain one or more layers. This vaginal ring may be made of any material suitable for the manufacture of such dosage forms. For example, a polymer that can be used in practice of the invention, can be, in principle, thermoplastic polymer or elastomer material suitable for pharmaceutical applications, for example low density polyethylene, ethylenevinylacetate copolymers, polysiloxane, polyurethane, polyacrylate, and block copolymers of styrene and butadiene with alternating blocks. In a specific embodiment, is applied ethylenevinylacetate SOPs shall liner (poly-EVA), which is commercially available for example under the trade name Elvax, Evatane, Lupolen, Movriton, Ultrathene, Ateva and Vestypar.

Therefore, a more accurate compliance becomes possible due to the application of the method of female contraception, in which dosage form begin to apply on the day indicated by the number "n+3", any month and take a day designated by the number "n", next month, where "n" is the number of months from 1 to 25, regardless of which month, and how re-perform during at least two cycles. When using this method of non-hormonal phase is a period of not more than 4 days.

This more accurate compliance becomes possible also thanks to the application of the method of female contraception, in which dosage form begin to apply on the day indicated by the number "m+4", any month and take a day designated by the number "m"of the next month, where "m" is the number of months from 1 to 24, regardless of which month, and how re-perform during at least two cycles. When using this method of non-hormonal phase is a period of not more than 5 days.

This more accurate compliance additionally is made possible by the application of the method of female contraception which drugs begin to apply on the day, indicated by "y+5", any month and take a day designated by the number "y"of the next month, where "y" is the number of months from 1 to 23, regardless of which month, and how re-perform during at least two cycles. When using this method of non-hormonal phase is a period of not more than 6 days.

This more accurate compliance additionally is made possible by the application of the method of female contraception, in which dosage form begin to apply on the day indicated by the number "z+6", any month and take a day designated by the number "z", the next month, where "z" is the number of months from 1 to 22, regardless of which month, and how re-perform during at least two cycles. When using this method, non-hormonal phase is a period of not more than 7 days.

The method in accordance with the present invention can be used in the continuation of any number of cycles, starting with at least two cycles, i.e. for two, three, four, five, six, etc. cycles. In a specific embodiment, the method is used for at least three cycles.

In the method in accordance with the present invention hormonal phase is not constant from month to month the HQ. In contrast, non-hormonal phase is constant between the calendar months. In spite of this in all variants of implementation anticipated by the present invention, is provided and, in some cases, even improved suppression of ovarian function (necessary for achieving contraception).

Thus, compliance becomes possible due to the fact that a woman can choose a specific day of the month, which she finds the most easy-to-remember number. This day will always extract dosage form. The contraceptive effectiveness is maintained for a period of contraception regardless of what hormonal phase is not constant from month to month, while non-hormonal phase is constant from month to month.

Therefore, for example, in the mode (n, n+3) a woman can choose as "n" is any number between 1 and 25, regardless of which month.

For example, the first of the month is the easiest-to-remember number. In this example, the mode (n, n+3) woman chooses 1 as n" 1, i.e. the first of the month. Then the dosage form is administered (begin to apply) in each 4-th day of the month ("n+3" is the number of the month). For example, the 4th January, 4 February, 4 March, etc. etc. Then the dosage form is extracted in each of the first the day of the month for example, 1 January, 1 February, 1 March, etc. etc. Therefore, the woman in this case must remember only two mentioned each month, namely, the 1st and 4th, regardless of the month. Without limiting the present invention below, on the assumption that the dosage form begin to apply on the fourth day of the month at the same time, when it is taken on the first day of the month, duration of hormonal phase is:

25 days in February,

- 26 days in February in a leap year,

- 27 days in April, June, September, November,

- 28 days in January, March, may, July, August, October, December.

Under the same assumption, the duration of hormone-free phase is constant and lasts for 3 days. If the time of application (the application) on the day of injection (applicability) is not the same as the extraction time on the day of extraction, hormone-free phase can be increased to a maximum of 4 days, when, for example, a woman retrieves the dosage form at 00.01 hours of the first day of the month and enters (starts the application) new dosage form at 23.59 hours on the fourth day of the month. Therefore, in the example of the mode (n, n+3), hormone-free interval is 3-4 days, but not more than 4 days.

For example, when considering the full (non-leap) year, starting the Osia in January, and on the assumption that the dosage form is introduced into the fourth day of each month at the same time, when it is taken on the first day of the next month, the mode (n, n+3) each month contains 3-day hormone-free period, and the following number of days of introducing hormones:

Jan.Feb.MarchAPR.MayJuneJulyAug.Saint.Oct.Nov.Dec.
282528272827282827282728

The principle modes (m, m+4), (y, y+5) and (z, z+6) is similar. In the mode (m, m+4) hormone-free phase is at least 4 days, but not more than 5 days, (y, y+5) hormone-free phase is at least 5 days but not more than 6 days, and (z,z+6) hormone-free phase is at least 6 days, but not more than 7 days.

Mode in accordance with the present invention provides at least two advantages: first, it is possible compliance, because the woman using a specific dosage form, much easier to remember that specific day of any month, she will have to extract (end use) dosage form, and after 3, 4, 5 or 6 days (depending on the woman), and it is also a fixed number of any month, the woman should enter (start application) pharmaceutical form. Secondly, the mode in accordance with the present invention preserves or enhances the suppression of follicular development through a longer period of installation of the dosage form and a shortened hormone-free period; in other words, the mode in accordance with the present invention saves or, in some cases, even increases the suppression of ovarian function.

In accordance with the present invention it is also proposed contraceptive set for female contraception that contains at least two dosage forms, each dosage form to be used in one of two consecutive cycles, and each dosage form should begin to apply the "n+3"th of the month to izvlekat "n"-th day of the next month, where "n" is the number of months from 1 to 25.

In accordance with the present invention it is also proposed contraceptive set for female contraception that contains at least two dosage forms, each dosage form to be used in one of two consecutive cycles, and each dosage form should begin to apply the "m+4"th of the month and remove the "m"-th of the following month, where "m" is the number of months from 1 to 24.

In accordance with the present invention further provides contraceptive set for female contraception that contains at least two dosage forms, each dosage form to be used in one of two consecutive cycles, and each dosage form should begin to apply the "y+5"th of the month and remove the y-th of the following month, where "y" is the number of months from 1 to 23.

In accordance with the present invention further provides contraceptive set for female contraception that contains at least two dosage forms, each dosage form to be used in one of two consecutive cycles, and each dosage form need to start using "z+6-month and remove the "z"-th next month is a, where "z" is the number of months from 1 to 22.

Contraceptive set in accordance with the present invention can provide any number of months, starting with a set of at least two cycles, i.e, a set of two, three, four, five, six, etc. cycles. If the set is composed of, for example, for three months, then, of course, each dosage form to be used in one of three consecutive cycles; if the set is composed of, for example, for four months, then each dosage form to be used in one of four consecutive cycles, etc.

In accordance with the present invention it is also proposed a system of reminders dosage regimen containing a selection of one particular of the month from 1 to 25, regardless of the month as a number, when the dosage form is always extracted, and a new dosage form always begin to apply within three days thereafter.

In accordance with the present invention further provides a reminder system dosing regimen containing a selection of one particular of the month from 1 to 24, regardless of the month as a number, when the dosage form is always extracted, and a new dosage form always begin to apply four days after this.

In accordance with the present invention further provides a system is and reminders dosage, containing a selection of one particular of the month from 1 to 23, regardless of the month as a number, when the dosage form is always extracted, and a new dosage form always begin to apply within five days thereafter.

In accordance with the present invention it is also proposed a system of reminders dosage regimen containing a selection of one particular of the month from 1 to 22, regardless of the month as a number, when the dosage form is always extracted, and a new dosage form always begin to apply six days after this.

In accordance with the present invention it is also proposed mode of contraception for dosage forms in accordance with the present invention, in which the hormones administered for a period of a certain length, wherein the length of the cycles change so as to match the number of days in the month that starts the cycle. A certain duration can be any number of months, starting with at least two months, i.e. two, three, four, five, six and tposana. In a specific embodiment, a defined duration is three months.

Below the present invention is additionally described by way of examples, which in no case are not intended to limit the volume of the mA of the invention, defined by the claims.

EXAMPLE 1

Pharmacodynamic study: n, n+3, where n=1

An open randomized comparative pharmacodynamic study performed during February, March and April months with commercially contraceptive vaginal ring (Nuvaring®) on a monthly basis in accordance with the present invention, the ring is administered every 4-th (n+3) of the month and then extract the first (n) of the next month, in comparison with the standard mode 21/7. The research is being done on healthy female volunteers to assess the impact of vaginal rings mentioned in the monthly mode on ovarian function (pharmacodynamics) in comparison with the effects on ovarian function standard mode 21/7.

Forty (40) healthy women in the premenopausal age from 18 to 40 years during the screening part of the study within three treatment cycles.

Women are divided into two groups, experienced A Department and an experienced branch B. Experimental Department uses A vaginal ring in standard mode, in which the ring is worn for 21 days, followed by 7 days without rings. Experienced branch B uses the vaginal ring mode in accordance with the present invention, in which the ring is introduced into each of the 4-th day of the month and retrieve each of the first first day of the following month.

Three times a week to measure the level of estradiol (E2), progesterone (P), LH (luteotropin) and FSH (follitropin) in serum and perform razvlekatelnoe ultrasound scan. Physical and gynecological examination performed at screening and at the end of the procedure, and when the screening test cervical Cytology.

EXAMPLE 2

Pharmacodynamic study: m, m+4, where m=1

An open randomized comparative pharmacodynamic study, essentially the same as in example 1, performed on a monthly basis in accordance with the present invention, the ring is injected every 5-th (m+4) of the month and then extract the first (m) next month, in comparison with the standard mode 21/7.

EXAMPLE 3

Pharmacodynamic study: y, y+5, where y=1

An open randomized comparative pharmacodynamic study, essentially the same as in example 1, performed on a monthly basis in accordance with the present invention, the ring is administered every 6-th (y+5) day of the month and then extract the first (y) of the next month, in comparison with the standard mode 21/7.

EXAMPLE 4

Pharmacodynamic study: z, z+6, where z=1

An open randomized comparative pharmacodynamic study, essentially the same as in example 1, perform in egemesachno the m mode in accordance with the present invention, when this ring is injected every 7-th (z+6) day of the month and then extract the first (z) of the following month, in comparison with the standard mode 21/7.

EXAMPLE 5

Experimental comparative study

Open randomized study conducted at several institutions in five departments with comparison groups, in the modes described in examples 1, 2, 3 and 4, in comparison with the standard mode 21/7 perform with the same commercially vaginal contraceptive ring to explore different monthly modes in accordance with the present invention in healthy female volunteers. The effectiveness of the contraceptive, the characteristics of vaginal bleeding, safety, compliance and tolerability mentioned various monthly modes are assessed in comparison with the standard mode 21/7.

Five hundred (500) healthy women in the premenopausal age from 18 to 40 years during the screening part of the study within one year, i.e. within 12 months for modes in accordance with the present invention or within 13 treatment cycles for standard mode 21/7.

Women are divided into five (5) groups:

experienced Department A: standard mode, 21 days of application of the ring, with the subsequent 7 days period without rings;

experienced Department B: egem the monthly mode in accordance with the present invention, in which the ring enter the 4th of each month (n+3) and extract the first day of the next month (n); (3-4-day period without rings);

experienced Department C: monthly mode in accordance with the present invention, in which the ring enter the 5th of each month (m+4) and extract the first day of the next month (m) (4-5-day period without rings);

experienced Department D: monthly mode in accordance with the present invention, in which the ring enter the 6th of each month (y+5) and extract the first day of the next month (y) (5-6-day period without rings);

experienced office E: monthly mode in accordance with the present invention, in which the ring enter the 7th of each month (z+6) and extract the first day of the next month (z) (6-7-day period without rings).

Assessment is carried out at screening (within one month before the procedure and at 3, 6, 9 and 12 months or premature termination. During his visit for screening surveyed medical and gynecological history and passed a medical and gynaecological examination, including cytological examination of the cervix. Medical and gynecological examinations were repeated during the last visit during the examination. In addition, during screening and at the end of the procedure, perform clinical laboratory is esti emissions. During all visits in the study measure blood pressure and body weight. During the screening and repeated a year later perform razvlekatelnoe ultrasound scan to assess endometrial thickness. Biopsy of the endometrium do, if the thickness of the two layers of the endometrium is 10 mm or more. Urine tests for pregnancy are the subjects before beginning the procedure of the study, during each visit during the study and if you suspect a pregnancy during the study. During the whole study register for the detection of side effects and the conduct of associated medical course. Picture of vaginal bleeding and compliance recorded in the diaries.

EXAMPLE 6

Study of safety and effectiveness: n, n+3, where n=1

Open randomized study conducted at several institutions in two branches with comparison groups, performed to examine the effectiveness of the contraceptive, the characteristics of vaginal bleeding, compliance, safety and tolerability with the same vaginal ring, which was used in examples 1-5, on a monthly basis in accordance with the present invention, the ring is administered every 4-th (n+3) of the month and extract each 1st (n) the number of the next month, and compared to the standard mode 21/7.

One thousand three hundred and thirty (1330) healthy women in the premenopausal age from 18 to 40 years during the screening part of the study within one year, i.e. within 12 months for modes in accordance with the present invention or within 13 treatment cycles for standard mode 21/7.

Women are divided into two (2) groups:

experienced Department A: 330 women participate in the study according to the standard mode, which includes 21 days of application of the ring and subsequent 7-day period without rings (i.e. hormone-free period);

experienced Department B: 1000 women participate in the study on a monthly mode in accordance with the present invention, in which the ring enter the 4th of each month (n+3) and extract the first day of the next month (n); (3-4-day period without rings);

assessment is carried out at screening (within one month before the procedure and at 3, 6, 9 and 12 months or premature termination. During his visit for screening surveyed medical and gynecological history and passed a medical and gynaecological examination, including cytological examination of the cervix. Medical and gynaecological examination and cytological examination of the cervix was repeated during the last visit during the examination. In addition, lying in the screening and at the end of the procedure, perform clinical laboratory tests emissions. During all visits in the study measure blood pressure and body weight. The urine test for pregnancy is tested before beginning the procedure of the study, during each visit during the study and if you suspect a pregnancy during the study. During the whole study register for the detection of side effects and the conduct of associated medical course. Picture of vaginal bleeding and compliance recorded in the diaries.

It is revealed that the investigated mode provides, as a result, very high compliance in comparison with standard mode 21/7.

EXAMPLE 7

Study of safety and effectiveness: m, m+4, where m=1

Open randomized study conducted at several institutions in two branches with comparison groups, essentially the same as described in example 6, is performed to examine the effectiveness of the contraceptive, the characteristics of vaginal bleeding, compliance, safety and tolerability with the same vaginal ring, which was used in examples 1-5, on a monthly basis in accordance with the present invention, the ring is injected every 5-th (m+4) number of months and extract each 1-th (m) is the number of the next month, and compared with the standard mode 21/7.

EXAMPLE 8

Study of safety and effectiveness: y, y+5, where y=1

Open randomized study conducted at several institutions in two branches with comparison groups, essentially the same as described in example 6, is performed to examine the effectiveness of the contraceptive, the characteristics of vaginal bleeding, compliance, safety and tolerability with the same vaginal ring, which was used in examples 1-5, on a monthly basis in accordance with the present invention, the ring is administered every 6-th (y+5) day of the month and retrieve every 1 second (y) the number of the next month, and in comparison with standard mode 21/7.

It is revealed that the investigated mode provides, as a result, very high compliance in comparison with standard mode 21/7.

EXAMPLE 9

Study of safety and effectiveness: z, z+6, where z=1

Open randomized study conducted at several institutions in two branches with comparison groups, essentially the same as described in example 6, is performed to examine the effectiveness of the contraceptive, the characteristics of vaginal bleeding, compliance is aswednesday and portability with the same vaginal ring, which was used in examples 1-5, on a monthly basis in accordance with the present invention, the ring is injected every 7-th (z+6) month and extract each 1-th (z) the number of the next month, and compared with the standard mode 21/7.

It is revealed that the investigated mode provides, as a result, very high compliance in comparison with standard mode 21/7.

1. A method of female contraception, which is that you begin to apply the dosage form per day, designated by the number "n+3", month, and extract dosage form per day, is indicated by "n", next month, where "n" is the number of months from 1 to 25, and in this way re-perform during at least two cycles.

2. A method of female contraception, which is that you begin to apply the dosage form per day, is indicated by "m+4", month, and extract dosage form per day, designated by the number "m"of the next month, where "m" is the number of months from 1 to 24, and in this way re-perform during at least two cycles.

3. A method of female contraception, which is that you begin to apply the dosage form per day, is indicated by "y+5", month, and extract dosage form per day, is indicated by "y", next month, where the y is the number of months from 1 to 23, and in this way re-perform during at least two cycles.

4. A method of female contraception, which is that you begin to apply the dosage form per day, is indicated by "z+6", month, and extract dosage form per day, is indicated by "z", the next month, where "z" is the number of months from 1 to 22, and in this way re-perform during at least two cycles.

5. The method according to claims 1 to 4, in which the dosage form is a vaginal ring.

6. The method according to claims 1 to 4, in which the application is vaginal introduction.

7. The method according to claims 1 to 4, in which the dosage form is a patch.

8. The method according to claims 1 to 4, in which the dosage form contains estrogen and progestogen.

9. The method according to claim 8, in which the progestogen is etonogestrel and the estrogen is estradiol or its salt, or a complex ester or estrogen is ethinyl-estradiol.

10. The method according to claim 8, in which the progestogen is nomegestrol acetate and the estrogen is estradiol or its salt, or a complex ester or estrogen is ethinyl-estradiol.

11. The method according to claim 5, in which the dosage form is made of a thermoplastic material.

12. The method according to claim 5, in which the dosage form contains one or more compartments.

13. The method according to A12, in which each compartment contains one or more layers.

14. Set for female contraception that contains at least two dosage forms and instructions that each dosage form to be used in one of two consecutive cycles and each dosage form should begin to apply the n+3-th day of the month and remove the "n"-th of the following month, where "n" is the number of months from 1 to 25.

15. Set for female contraception that contains at least two dosage forms and instructions that each dosage form to be used in one of two consecutive cycles and each dosage form should begin to apply the "m+4"th of the month and remove the "m"-th of the following month, where "m" is the number of months from 1 to 24.

16. Set for female contraception that contains at least two dosage forms and instructions that each dosage form to be used in one of two consecutive cycles and each dosage form should begin to apply the "y+5"th of the month and remove the y-th of the following month, where "y" is the number of months from 1 to 23.

17. Set for female contraception that contains at least two dosage forms and instructions that each dosage form under EIT application in one of two consecutive cycles and each dosage form need to start using "z+6-month and remove the "z"-th day of the next month, where "z" is the number of months from 1 to 22.

18. The contraceptive kit according to any one of p-17, which contains three dosage forms.

19. Set according to any one of p-17, in which the dosage form is a vaginal ring.

20. Set according to any one of p-17, in which the application is vaginal introduction.

21. Set according to any one of p-17, in which the dosage form is a patch.

22. Set according to any one of p-17, in which the dosage form contains estrogen and progestogen.

23. Set by article 22, in which the progestogen is etonogestrel and the estrogen is estradiol or its salt, or a complex ester or estrogen is ethinyl-estradiol.

24. Set by article 22, in which the progestogen is nomegestrol acetate and the estrogen is estradiol or its salt, or a complex ester or estrogen is ethinyl-estradiol.

25. Set according to claim 19, in which the dosage form is made of a thermoplastic material.

26. Set according to claim 19, in which the dosage form contains one or more compartments.

27. Set p, in which each compartment contains one or more layers.

28. The reminder system dosage installed in such a way that allows you to choose a specific day of the month from 1 to 25, regardless of the month as a number, when the medicament is i.i.d. form always extract, and the introduction of a new dosage form within three days thereafter.

29. The reminder system dosage installed in such a way that allows you to choose a specific day of the month from 1 to 24, regardless of the month as a number, when the dosage form is always extracted, and the introduction of a new dosage form four days after this.

30. The reminder system dosage installed in such a way that allows you to choose a specific day of the month from 1 to 23, regardless of the month as a number, when the dosage form is always extracted, and the introduction of a new dosage form within five days thereafter.

31. The reminder system dosage installed in such a way that allows you to choose a specific day of the month from 1 to 22, regardless of the month as a number, when the dosage form is always extracted, and the introduction of a new dosage form six days after this.

32. System reminders PP-31, in which the dosage form is a vaginal ring.

33. System reminders PP-31, in which the application is vaginal introduction.

34. System reminders PP-31, in which the dosage form is a patch.



 

Same patents:

FIELD: medicine.

SUBSTANCE: multiphase pharmaceutical preparation for ovulation inhibition in mammal contains a number of individually packed and individually removed daily units placed in a single package, and used for oral administration for at least 21 days running; specified daily units contain a combination of oestradiol and drospirenone. A daily unit contains 0.5 to 4 mg of oestradiol and 2 to 4 mg of drospirenone. At least 70% of specified drospirenone are released from specified unit within 30 minutes.

EFFECT: invention provides higher oral bioavailability of drospirenone.

6 cl, 5 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: there is claimed application of ethinylestradiol and chlormadinone acetate combination for obtaining medication applied simultaneously for treatment of androgen-induced disorders, for substitution hormonotherapy, for treatment of dismenorea, for stabilisation of menstrual cycle, for treatment of illnesses dependent on menstrual cycle and for women's contraception, said medication being obtained in form of at least 21 hormone-containing day dose, and said combination of hormones contains from 5 to 20 mcg of ethinylestradiol and from 1 to 5 mg of chlormadinone acetate in day dose, if necessary in combination with 7-3 day doses which do not contain hormone.

EFFECT: it is demonstrated that reduction in claimed medication of ethinylestradiol amount does not influence cycle stabilisation, but it can be continuously introduced to women in pre- and perimenopause in order to achieve simultaneously all said aims, as well as for reduction of high blood pressure.

11 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to steroids with (11β)-[4-(aza-aryl)phenyl] substitutes which modulate progesterone receptors, or pharmaceutically acceptable salts and/or hydrated form, and/or prodrug thereof.

EFFECT: compounds exhibit combined activity profile of PR agonist and PR antagonist which makes them suitable for contraception and treating gynaecological disorders.

30 cl, 28 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention distinguishes 28-day and 91-day modes of taking combined oral contraceptives, possibly in combination with antidepressant (fluoxetine hydrochloride) in which full disappearance of estrogen from preparation does not take place. This presupposes that shorter influence of peaks and drops of endogenic progesterone protects against premenstrual disphoric disorder (PMDD) and against symptoms of mood disturbance in women with PMS.

EFFECT: application of estrogen and progesterone for manufacturing medication for contraception, treatment of premenstrual syndrome (PMS) or syndrome of estrogen cessation (versions), respective preparation (versions) and method of pregnancy prevention.

91 cl, 6 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: invention is related to the field of medicines, in particular to tetrahydroquinoline derivatives with common formula (I), where Y-X means C(O)-O, C(O)-NH, S(O)2-NH, NHC(O)-NH, NHC(S)-NH, OC(O)-NH; R6 stands for H, (1-6C)alkyl, 1- or 2-adamantyl(1-4C)alkyl, (3-9C)heteroaryl, (3-6C)cycloalkyl, (2-6C)heterocycloalkyl, alkylthio(1-4C)alkyl, phenyl(1-4C)alkyl, (3-6C)cycloalkyl (1-4C)alkyl, (2-6C)heterocycloalkyl (1-4C)alkyl, R8, R9 aminocarbonyl (1-4C) alkyl, R8, R8R9-amino (1-4C)alkyl, R8-oxycarbonyl (1-4C)alkyl, R8-oxy (1-4C)alkyl, R8-carbonyl (1-4C)alkyl or phenyl, not necessarily substituted with hydroxy, amino, halogen, nitro, trifluoromethyl, (3-9C)heteroaryl, (1- 4C)alkylcarbonylamino, (1-4C)alkylcarbonyloxy, (3-9C)heteroarylcarbonyloxy, (3-9C)heteroarylsulfonyloxy, (2-6C)heterocycloalkylcarbamoyl or diphenylamino.

EFFECT: modulating activity in respect to FSH receptor.

17 cl, 74 ex

FIELD: medicine; pharmacology.

SUBSTANCE: mainly water-free composition for oral or vaginal mucosa lubrication includes at least one polyatomic alcohol and honey as insulation agent. Invention also concerns methods of the composition application for lubrication, active component introduction and dysmenorrhea prevention or treatment. Methods involve application of mainly water-free lubricating composition including at least one polyatomic alcohol and insulation agent selected from honey and isopropylpalmitate, onto oral or vaginal mucosa to produce heating effect.

EFFECT: reduced toxicity and irritation effect.

31 cl, 1 tbl, 9 ex

FIELD: medicine; pharmacology.

SUBSTANCE: system of delivery of medicinal substance includes one department consisting from (i) of a kernel from thermoplastic polymer, filled with medicinal substance, (ii) an intermediate layer from the thermoplastic polymer filled with medicinal substance, and (iii) covers from the thermoplastic polymer, covering an intermediate layer and not containing medicinal substance, where the specified intermediate layer is filled (a) with crystals of the first pharmacologically active substance, and (b) the second pharmacologically active substance in the dissolved form and where the kernel is filled specified to the second pharmacologically active substance in the dissolved form. The delivery system is intended for vaginal introduction of the medicinal substance.

EFFECT: possibility of adjustment of rate of liberation of two or more active ingredients irrespective of others, at maintenance of long physical stability of system at room temperature.

51 cl, 21 dwg, 10 tbl, 4 ex

FIELD: medicine; pharmaceutics.

SUBSTANCE: invention refers to pharmacology and medicine and concerns ethonogestrel new esters of formula 1 , 2 , 3 , applied for male and female contraception. Compositions are characterised by improved disposition profile.

EFFECT: production of composition with improved disposition profile.

3 cl, 2 dwg, 1 ex

Spermicidal agent // 2315602

FIELD: medicine.

SUBSTANCE: invention relates to contraceptive agents. Invention reports the presence of spermicidal activity in sulfacyl-sodium (para-aminobenzene sulfacetamide-sodium known as sodium sulfacetamide also) and momentary death of sperms at concentration of sulfacyl-sodium from 20% and above. The combination of this activity with the known early antiprotozoan and antibacterial effect with respect to gonococci, chlamydiae, streptococci and staphylococci sulfacyl-sodium enhances its significance as vaginal contraceptive agent essentially and shows absence of such adverse effects as irritation, allergic responses, burning and intense itching.

EFFECT: valuable properties of agent.

1 tbl

FIELD: medicine.

SUBSTANCE: method involves administering hormone composition comprising 0.5-3.0 mg of estrogen (estradiol, free or etherified conjugated horse estrogen) and 1.5-3.75 mg of nomegestrol acetate for treating estrogen insufficiency cases and stopping ovulation.

EFFECT: enhanced effectiveness of treatment in menopause period without bleeding.

8 cl, 6 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to chemical-pharmaceutical industry, and concerns a transbuccal delivery system including a matrix of: (a) an effective amount of one or more active ingredients; (b) an amount of one or more polyethylene glycols or their derivatives of molecular weight within 1000 to 8000, sufficient to maintain the required hardness and matrix disintegration; (c) 0.05-2 wt % of one or more suspending agents of matrix mass; (d) 0.05-2 wt % of one or more liquidity agents of matrix mass; and (c) 0.05-2 wt % of one or more sweeteners of matrix mass.

EFFECT: development of the transbuccal delivery system to be prepared conventionally, preparation of a dry powder and enabled pressing with applying a common device for tablets manufacturing.

25 cl, 4 ex, 6 dwg, 5 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to gynaecology, and may be used for treatment of benign diseases of uterine neck. For this purpose after basis therapy with radio wave method of treatment, from the first days the female patients use hormonal therapy with single-phase contraceptives.

EFFECT: invention makes it possible to reduce time of postoperational wound epithelisation and to reduce frequency of uterine neck diseases relapses.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine, in particular to gynecology and deals with hormonal treatment of disease or disorder and increase of fertility in woman who needs it. For this purpose, regimens of continuous with more than 50-day duration introduction of combination of ethinylestradiole in dose from 5 mcg to 50 mcg and levonorgestrel in dose from approximately 0.05 mg to approximately 1.5 mg is suggested. Further, estrogen is introduced during period from 2 to 10 successive days.

EFFECT: due to "estrogen bridge" between cycles of hormonal therapy, inventions ensure reduction of number of unplanned bleedings in second and following cycles of intake in comparison with regimens, which include after the cycle finishing days, free of hormonal therapy, and minimisation of symptoms, conditioned by break between cycles.

64 cl, 10 dwg, 21 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine, in particular to gynecology and deals with hormonal treatment of disease or disorder and increase of fertility in woman who needs it. For this purpose, regimens of continuous with more than 50-day duration introduction of combination of ethinylestradiole in dose from 5 mcg to 50 mcg and levonorgestrel in dose from approximately 0.05 mg to approximately 1.5 mg is suggested. Further, estrogen is introduced during period from 2 to 10 successive days.

EFFECT: due to "estrogen bridge" between cycles of hormonal therapy, inventions ensure reduction of number of unplanned bleedings in second and following cycles of intake in comparison with regimens, which include after the cycle finishing days, free of hormonal therapy, and minimisation of symptoms, conditioned by break between cycles.

64 cl, 10 dwg, 21 tbl, 10 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to oncology, and can be used for treating brain glioma. For this purpose after tumour ablation glucocortocoids are introduced intramuscularly daily and radiotherapy is carried out. Before beginning irradiation and in process of treatment every 7-10 days blood serum is applied on transparent surface, dried at 20 - 25°C and relative humidity 55 - 60% and microscopic image of blood serum fascies is analysed. If in sample in process of irradiation leaf-shaped structures appear or their number increases in comparison with sample before irradiation less than 2 times, additionally trental is introduced intravenously in dose 100-200 mg twice per week. If number of said structures in sample increases 2 times and more trental is introduced intravenously in dose 200-300 mg twice per week and actovegin is introduced in dose 400 mg daily. Medications are introduced before finishing course of radiotherapy.

EFFECT: increase of treatment efficiency and possibility to carry out complete course of radiotherapy due to individual control of state of microcirculatory brain bed and depth of its injuries, cause by radiotherapy, which allows to carry out their drug correction in due time in accordance with individual programme.

4 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed group of inventions relates to medicine, namely to oncology, and can be used for treatment of metastatic neoplastic disease. Claimed is treatment method which includes introduction of therapeutically efficient quantity of sodium meta-arsenite. Additionally introduction of other chemotherapeutical substance is carried out. Claimed is composition, containing sodium meta-arsenite. Claimed is set for inhibition of abnormal cell growth, which includes therapeutically efficient quantity of pharmaceutical composition, containing sodium meta-arsenite, and other chemotherapeutical substance.

EFFECT: group of inventions ensures possibility of metastatic neoplastic disease treatment with alternative compound with anticancer activity, as well as treatment safety.

2 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to gastroenterology, and can be used for treatment of cholelithiasis after cholecystectomy. For this purpose at the background of keeping to sparing diet ursosan capsules are introduced orally in dose 10 mg per 1 kg of body weight per day. Additionally, irrespective of patient's psychoemotional state, medication atarax is introduced orally in dose 25 mg 2 times per day in the morning and in the evening for 30 days.

EFFECT: method ensures prevention of post-cholecystectomy syndrome due to stable normalisation of function of vegetative nervous system, improvement of motor function of biliary tract, normalisation of sphincter of Oddi function, improvement of bile outflow and reduction of number of complications.

3 tbl

FIELD: medicine.

SUBSTANCE: method involves polychemotherapy followed by radiation therapy (RT) with underlying plant-based mouth rinsing and oral administration of Colegel with Derinat and Lidocaine 3 times a day and more often. The polychemotherapy is performed by no more than 2 courses with the radiation started not earlier than in 10-15 days after the polychemotherapy to total basic dose 66-70 Gy and with peripheral blood of an exposed patient analysed for lymphocyte count once in 10 days and more often. If lymphocyte count is 1.2×109/l or less, the following RT sessions are carried out with underlying additional intensive local and system therapy, or the therapy is interrupted for the hemostimulation therapy.

EFFECT: use of the invention allows preventing severity gain in a radiation involvement of oropharyngeal mucosa due to well-timed intensification of local and system therapy, performing a radical RT course and improving clinical effectiveness.

2 cl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to oncology and can be used for optimisation of Hodgkin's lymphoma of IIIA stage treatment in adults. Method is realised in the following way. In case there are no symptoms of intoxication, patients with histological subtype nodular sclerosis and with histological grade at which 75% and more of cellular nodules contain only dispersed Berezovsky-Stenberg cells located on rich in lymphocytes mixed cellular or fibrohistiocytic background, 2-3 cycles of introductory combined chemical therapy are carried out according to schemes MOPP, MOPPABV or ABVD. After that total or subtotal irradiation of lymphatic nodules is performed.

EFFECT: application of invention allows to determine indications for chemical-radiological therapy taking into account versions of histological structure of tumour, ensures long-term recurrence-free survival rate and reduces treatment toxicity.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to gastroenterology and deals with methods of treating patients with intestinal dysbacteriosis. For this purpose ursofalk in dose 1 capsule 3 times a day is introduced during one month.

EFFECT: method ensures restoration of quantitative and qualitative ratio of bile acids in intestine, antiseptic effect in intestine, normalising killing activity of lymphocytes and, as a result, creates optimal conditions for restoration of microbiocoenosis.

3 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to chemical-pharmaceutical industry, and concerns a transbuccal delivery system including a matrix of: (a) an effective amount of one or more active ingredients; (b) an amount of one or more polyethylene glycols or their derivatives of molecular weight within 1000 to 8000, sufficient to maintain the required hardness and matrix disintegration; (c) 0.05-2 wt % of one or more suspending agents of matrix mass; (d) 0.05-2 wt % of one or more liquidity agents of matrix mass; and (c) 0.05-2 wt % of one or more sweeteners of matrix mass.

EFFECT: development of the transbuccal delivery system to be prepared conventionally, preparation of a dry powder and enabled pressing with applying a common device for tablets manufacturing.

25 cl, 4 ex, 6 dwg, 5 tbl

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