CN101394845A - Extended cycle multiphasic oral contraceptive method - Google Patents
Extended cycle multiphasic oral contraceptive method Download PDFInfo
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- CN101394845A CN101394845A CNA2007800075523A CN200780007552A CN101394845A CN 101394845 A CN101394845 A CN 101394845A CN A2007800075523 A CNA2007800075523 A CN A2007800075523A CN 200780007552 A CN200780007552 A CN 200780007552A CN 101394845 A CN101394845 A CN 101394845A
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Abstract
A multiphasic method of contraception comprising the steps of sequentially administering to a female of child bearing age a Phase I composition containing a progestogen in an amount equivalent to about 0.3 to about 1.5 mg norethiiidrpne acetate and an estrogen in an amount equivalent to about 5 to abo[mu]t 15 mcg of ethinyl estradiol for about 7 to about 14 days; a Phase II composition containing a progestogen in an amount equivalent to about 0.3 to about 1.5 mg of norethindrone acetate and an estrogen in an amount equivalent to about 10 to about 25 meg of ethinyl estradiol for about 14 to about 22 days; a Phase m composition containing a progestogen in an amount equivalent to about 0.3 to about 1.5 mg of norethindrone acetate and an estrogen in an amount equivalent to about 15 to about 35 meg of ethinyl estradiol for about 20 to about 31 days; and an optional Phase IV composition containing (i) an estrogen in an amount equivalent to about 5 to about 20 meg of ethinyl estradiol, or (ii) a placebo or a non-steroidal component, or (iii) a combination of (i) and (ii), for about 2 to about 8 days. The ethinyl estradiol equivalent amount of estrogen in each of the successive Phases II and III is at least 5 meg greater than the ethinyl estradiol equivalent amount of estrogen in the immediately-preceding phase.
Description
The priority of the U.S. Provisional Application 60/792,653 that the application requires to submit on March 2nd, 2006 U.S. Provisional Application was submitted on April 18th, 60/778,067,2006, with them with integral body by with reference to being incorporated herein.
Technical field
[0001] the present invention relates to be used for the multistage estrogenic/progestogenic contraceptive regimen of long period.In multistage therapy of the present invention, the amount of estrogen of using in each successive stages of pro-three phases is greater than the amount of estrogen of using in the last stage.Therapy of the present invention provides contraceptive efficacy, makes user can keep control to menstrual cycle.The multistage contraceptive medicine box that is used to implement the inventive method also is considerable.
Technical background
[0002] the known composition for contraception that comprises estrogen and progestogenic compounds is highly effective for controlling ovulation and becoming pregnant.The progestogen component of said composition plays a major role for the contraceptive effect of compositions, and included estrogenic component is to be used to reduce undesirable side effect, for example break-through bleeding or dripping hemorrhage.In fact, a spot of estrogen helps to stablize endometrium and allows and calendar month cycle withdrawal bleeding like the periodic group.
[0003] estrogen the earliest and progesterone composition adopt single phase administration (fixed dosage), and wherein contained estrogenic component is tied higher mutually.For estrogen is minimized for the major side effects of blood clotting factors, can reduce estrogenic dosage with the prolongation of Time of Administration.Yet, when estrogen dosage reduces, can increase undesirable break-through bleeding or dripping hemorrhage incidence rate usually.
[0004] can introduce the rising naturally that the multistage oral contraception comes manual simulation progesterone in the cycle, address the above problem with trial.But constant target is the estrogenic effect that reduces in these compositionss, and does not reduce contraceptive effect and do not increase adverse side effect.
[0005] at US 5,888, in 543, disclosed different therapies, wherein progestogen and estrogenic combination are used with single phase or multistage therapy (variable dose, for example two-stage or three stages).In one embodiment, combined administration with progesterone composition and estrogen compositions, so that the second stage progestogen every day dosage greater than dosage every day of progestogen in the phase I, second stage estrogenic every day of dosage more than or equal in the phase I estrogenic every day dosage.
[0006] US 4,962, and 098 has described a kind of particularly advantageous technology can reduce estrogenic total amount of application.It has described a kind of triphasic contraceptive regimen, comprises the combination of using progestogen/estrogen, and wherein estrogenic amount progressively increases in three phases.Phase I is 4-7 days, and second stage is 5-8 days, and the phase III is 7-12 days.Preferably, after being used for this triphasic composition for contraception and using 21 days, next be 7 days placebo period.For all three phases, progestogen are 0.5 to the 1.5mg norethindrone acetate, and what use in the phase I is about 10 to the 30mcg ethinylestradiol, and what use in second stage is about 20 to 40mcg ethinylestradiol, and what use in the phase III is 30 to 50mcg ethinylestradiol.
[0007] US 5,010, and 070 is relevant with US 4,962,098, and it has disclosed a kind of multistage contraceptive medicine box, in phase I, second stage with comprise ethinylestradiol and norethindrone acetate in the phase III.
[0008] recent, several oral contraceptive regimen known in the art, extended treatment to 3 cycle.US 5,898, and 032 has disclosed a kind of OCT of prolongation, and wherein estrogen and progestogen are used according to combination dosage forms, are preferably single phase to use, and continuous administration 60-110 days, next stop to use 3-10 days.Estrogen and progestogen amount of application every day are equivalent to about 5-35mcg ethinylestradiol and 0.025 respectively to the 10mg norethindrone acetate.In a special embodiment, combination dosage forms was used 84 days, next stopped to use 7 days of pill.According to described this special therapy, 4 treatments and menstrual cycle have been caused during 1 year, producing.
[0009] the another kind of OCT that prolongs provides in US 2005/0113350 A1, and the successive hormone treatment therapy of time above 21-28 days in expectation is provided.At this, first compositions comprises Progesterone and estrogen, used at initial 21-28 days, and be Progesterone and estrogenic second compositions then, its amount is higher than the amount of first compositions, comprises the dosage of list or multistage sequence.Preferred Therapeutic Method is included in persistent period of 84-112 days and uses described dosage.
[0010] still, it is imperfect using the single phase oral contraception method that prolongs.Typically, the single phase oral contraceptive of using in the long period has very poor initial period control.
[0011] in addition, although the number of times in menstrual period may be reduced to annual 4 times, prolong above 3 cycles conventional single phase the oral contraception method another shortcoming be often to cause over-drastic break-through bleeding.Break-through bleeding or dripping hemorrhage be do not expect hemorrhage, take place in withdrawal bleeding phase of routine sometimes.It is believed that the extended treatment that surpasses 1 month during the phase, break-through bleeding is difficult to suppress effectively gradually.When using a lot of three-cycle during method, when treatment begins collapse until stop oral contraception when the period 3 finishes, the frequency of irregular bleeding generation increases gradually, causes occurring undesirable withdrawal bleeding at last.The estrogen of high dose can reduce over-drastic break-through bleeding although use more, and this also brings the danger of higher estrogen to the adverse side effect of thrombin inevitably.At last, in case controlled break-through bleeding, user will functional menolipsis so.This will make user can not confirm not have pregnancy psychologically.
[0012] therefore, need a kind of OCT of prolongation, it can significantly reduce the generation that generally prolongs the relevant break-through bleeding of cycle therapy with three-moon, and only need increase estrogenic dosage gradually along with the process of treatment simultaneously.
Summary of the invention
[0013] the present invention relates to a kind of multistage contraceptive device, comprise jenny to reproduction age use (a) Phase I composition continuously, comprise progestogen, in an amount equivalent to the about 1.5mg norethindrone acetate of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 15mcg of about 5-, used about 7-about 14 days; (b) the Phase compositions comprises progestogen, in an amount equivalent to the norethindrone acetate of the about 1.5mg of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 25mcg of about 10-, used about 14-about 22 days; (c) Phase I compositions comprises progestogen, in an amount equivalent to the norethindrone acetate of the about 1.5mg of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 35mcg of about 15-, used about 20-about 31 days; (d) optional, but it is preferred, Phase IV composition, comprise (i) estrogen, in an amount equivalent to the ethinylestradiol of the about 20mcg of about 5-, or (ii) placebo or on-steroidal component, or (iii) (i) and combination (ii), used about 2-about 8 days, wherein in each stage of continuous stages II and III estrogenic ethinylestradiol equivalent proportion at adjacent estrogenic ethinylestradiol equivalent in the last stage greatly at least about 5mcg.
[0014] in significant especially embodiment of the present invention, the Phase I of continuous administration, II, III and IV compositions are successive, until finishing using of Phase IV composition, so that a kind of multiphasic oral contraceptive method that prolongs the cycle to be provided.Preferably, the scope that comprises the prolongation contraceptive cycle of optional Phase IV composition is about 62 days of about 52-, and more preferably from about 54-is about 58 days, even about 57 days of more preferably preferably about 55-, most preferably from about 56 days.
[0015] another embodiment of the invention relates to a kind of multistage combination and contraceptive medicine box, comprises a packing, and wherein comprise: (a) Phase I composition of about 14 daily doses of about 7-comprises progestogen, in an amount equivalent to the about 1.5mg norethindrone acetate of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 15mcg of about 5-; (b) the Phase compositions of about 22 daily doses of about 14-comprises progestogen, in an amount equivalent to the norethindrone acetate of the about 1.5mg of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 25mcg of about 10-; (c) the Phase I compositions of about 31 daily doses of about 20-comprises progestogen, in an amount equivalent to the norethindrone acetate of the about 1.5mg of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 35mcg of about 15-; (d) optional but preferred, the Phase IV composition of about 8 daily doses of about 2-, comprise: (i) estrogen, ethinylestradiol in an amount equivalent to the about 20mcg of about 5-, or (ii) placebo or on-steroidal component, or (iii) (i) and combination (ii), wherein in each stage of continuous stages II and III estrogenic ethinylestradiol equivalent proportion at adjacent estrogenic ethinylestradiol equivalent in the last stage greatly at least about 5mcg.Phase IV composition does not contain progestogen substantially, that is, do not exist with the treatment effective dose.
[0016] medicine box is to be designed for the use of prolongation cycle.This medicine box preferably comprises the Phase I composition of about 14 dosage of about 7-; The Phase compositions of about 22 dosage of about 14-; The Phase IV composition of the Phase I compositions of about 31 dosage of about 20-and about 8 dosage of about 2-.
An advantage of the invention is that [0017] it has reduced the number of times of withdrawal bleeding about 50%, becomes annual about 6 to 7 times, also makes the amount of break-through bleeding minimum to identical with the OCT that prolongs simultaneously.
[0018] another advantage of the present invention is, it extends to contraceptive regimen more 2 months of practicality, has therefore avoided the general a lot of irregular bleedings relevant with 3-cycle stretch-out therapy.
[0019] another advantage of the present invention is that it provides quadravalence section in the end can change the selection of chemical compound, comprise estrogen than low dosage, independent placebo or both some compositions, this depends on the women of child-bearing age's that use methods described herein individual need.
The specific embodiment
[0020] according to purpose of the present invention, unit " mcg " refers to microgram, and " mg " refers to milligram.
[0021] by implementing multistage contraceptive device as herein described, user can be when taking estrogenic/progestogenic contraceptive compositions of the present invention, advantageously control withdrawal bleeding (being called menses sometimes), the number of times with withdrawal bleeding reduces to annual 6 to 7 times simultaneously.
[0022] noticeable feature of the present invention is the pro-three phases, in each compositions of continuous stages II and III estrogenic amount of application greater than adjacent in the last stage compositions estrogenic amount of application.In addition, reduced the equivalent of the ethinylestradiol of 5mcg at least than adjacent in the last stage (Phase I), preferably at least about 10mcg, most preferably at least about 15mcg in the estrogenic amount of four-stage (Phase IV).In an especially preferred embodiment, in the compositions of continuous stages II and III the amount of ethinylestradiol than adjacent in the last stage compositions amount of ethinylestradiol greatly at least about 5mcg, preferably greatly at least about 10mcg.
[0023] in an especially preferred embodiment, estrogenic amount is equivalent to about 10mcg ethinylestradiol in Phase I, estrogenic amount is equivalent to about 20mcg ethinylestradiol in Phase, estrogenic amount is equivalent to about 30mcg ethinylestradiol in Phase I, and estrogenic amount is equivalent to about 15mcg ethinylestradiol in Phase IV.In another particularly preferred embodiment, estrogenic amount is equivalent to about 10mcg ethinylestradiol in Phase I, estrogenic amount is equivalent to about 20mcg ethinylestradiol in Phase, estrogenic amount is equivalent to about 30mcg ethinylestradiol in Phase I, and does not give estrogen in Phase IV.
[0024] progestogen can be selected from, for example norethindrone acetate, drospirenone, trimegestone, norethindrone, levonorgestrel, desogestrel, 3-keto-desogestrel, gestodene etc.Other representational progestogen comprise demegestone, dydrogesterone, medrogestone, medroxyprogesterone and ester thereof.Most preferred progestogen are norethindrone acetates.Estrogen can be selected from, for example ethinylestradiol, 17-, estradiol acetate, conjugated estrogen, mestranol, estrone and esters prodrug and/or salt.Representational ester is an estradiol acetate.Most preferred estrogen is ethinylestradiol.Set, progestogen and estrogenic use amount are the amounts that is equivalent to norethindrone acetate and ethinylestradiol on usefulness respectively in each stage herein.Quite definite method of effect is well-known, and those of ordinary skills are easy to and can realize.
[0025] in women's body, contain the abundant uterine mucosa internal layer of blood and be called endometrium, regulate estrogenic varying level in vivo.It is believed that a lot of relevant with the most conventional oral contraception hemorrhage be by early stage exogenous estrogenic excessive adjusting causes in the cycle.Do not wish bound by theory, it is believed that, by making estrogenic amount circulation can when treatment begins, transmit less dosage, increase to higher dose levels then gradually, endometrium has been subjected to support, until when treatment finishes, stopping estrogenic using (for example, the estrogenic amount with Phase IV is reduced to and the similar level of Phase I or lower).
[0026] by in the about 60 days scope of about 50-, coming to stimulate endometrium to avoid too early overstimulation with exogenous estrogen by progressively increasing of dosage, it is believed that, endometrial integral body can remain at least about 3 to the thick appropriate state of 5mm, can reduce the generation of undesirable break-through bleeding like this.In the time can keeping her endometrial integrity in about 2 months time, the women is control over bleeding and prolong her cycle better.Increase estrogenic dosage gradually and can make endometrium adapt to the estrogen dosage of constant until drug withdrawal, prolong OCT to about 2 more than the cycle, the number of times that reduces withdrawal bleeding is to annual about 6 times.Bound by theory not, the adjusting up and down that it is believed that estrogen receptor has caused endometrial support and has reduced break-through bleeding.
[0027] multistage contraceptive device of the present invention comprises the continuous administration to the women of child-bearing age: (a) Phase I composition comprises progestogen, in an amount equivalent to the about 1.5mg norethindrone acetate of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 15mcg of about 5-, used about 7-about 14 days; (b) the Phase compositions comprises progestogen, in an amount equivalent to the norethindrone acetate of the about 1.5mg of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 25mcg of about 10-, used about 14-about 22 days; (c) Phase I compositions comprises progestogen, in an amount equivalent to the norethindrone acetate of the about 1.5mg of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 35mcg of about 15-, used about 20-about 31 days; (d) optional but preferred Phase IV composition, comprise: (i) estrogen, ethinylestradiol in an amount equivalent to the about 20mcg of about 5-, or (ii) placebo or on-steroidal component, or (iii) (i) and combination (ii), used about 2-about 8 days, wherein in each stage of continuous stages II and III estrogenic ethinylestradiol equivalent proportion at adjacent estrogenic ethinylestradiol equivalent in the last stage greatly at least about 5mcg.
[0028] can implement this therapy according to the mode in the cycle of prolongation.Phase I was used about 7-about 14 days, and Phase was used about 14-about 22 days, and Phase I used about 20-about 31 days, if use, Phase IV was used about 2-about 8 days.In fact, these stages are to carry out continuously by increasing order (that is, I, II, III and IV).Preferably, the time that can continue is about 52 days-Yue 62 days, and more preferably from about 54-is about 58 days, even about 57 days of 55-more preferably from about, most preferably from about 56 days.Wish to end this therapy and experience when hemorrhage when user, she both can begin the compositions of application stages IV, also can the about 2-of withdrawal about 8 days, and about 8 days of preferably about 4-.By implementing this therapy, user can reduce her menstrual cycle number of times, will have only 6 every year.
[0029] in the present invention, in that (for example estrogenic at least amount is equivalent to the ethinylestradiol of 5 μ g with low dosage, estrogen dosage less than Phase I) when using estrogen, Phase IV composition can constitute the final stage in prolongation cycle, perhaps alternately, Phase IV can be used as a cleaning phase and utilizes.In this stage, can choose wantonly and use placebo or non-steroidal component.
[0030] in Phase IV, can there be three kinds of different treatments to select.As the final stage in the cycle of prolongation, estrogenic amount can be low to moderate the amount that is equivalent to the about 20mcg ethinylestradiol of about 5-, uses about 2-about 4 days, uses the about 2-of placebo then about 4 days.Alternately, in about 8 days of about 2-of persistent period of all stage IV, estrogenic amount can be equivalent to the about 20mcg ethinylestradiol of about 5-, and does not use any placebo.As the third selection, in Phase IV, do not use estrogen, and only take placebo, used about 2-about 8 days.
[0031] in a preferred embodiment, estrogenic amount is equivalent to the ethinylestradiol of about 15mcg in Phase IV composition, and the phase of using is about 4 days of about 2-, and the estrogenic any given day of not using in Phase IV is used placebo.
[0032] in another preferred embodiment, estrogenic amount is equivalent to the ethinylestradiol of about 15mcg in Phase IV composition, and the phase of using is about 8 days of about 2-.
[0033] in another preferred embodiment, the placebo of optional Phase IV composition was used about 2-separately about 8 days, without any the estrogen equivalent.
[0034] in an especially preferred embodiment, the placebo of Phase IV composition is the non-steroidal component that comprises the ferrum additive.Suitable ferrum additive comprises, for example, and ferrous fumarate, ferrous sulfate, Ferrous gluconate, ferrum polysaccharide and their mixture.Preferred ferrum additive is a ferrous fumarate.
[0035] preferably, the ferrum additive is equivalent to no more than about 75mg ferrous fumarate.
[0036] as mentioned above, the in fact enforcement of the inventive method comprises with the numerical order applying said compositions, at first application stages I compositions, secondly application stages II compositions or the like.If pack and/or have other requirement, above-mentioned method and medicine box can be used as the part of a bigger contraceptive regimens or gynecopathy therapeutic.Though the order of administration of the application's compositions is important for its operation, should keep firmly in mind, when the consideration of medical science aspect, time and dosage are changed also and can allow.
[0037] though exemplary in the present invention estrogen compound is an ethinylestradiol, as long as should be appreciated that what use is the estrogen of equivalent, also can substitute with other estrogen compound.
[0038] similarly, norethindrone acetate is a progestogenic compounds exemplary among the present invention.
[0039] when using quadravalence section system, the compositions that the present invention uses in the Phase IV in Phase I more preferably has time of application as shown in table 1 and medicament contg.The correlation that sets in each table is used for the system that jenny is used corresponding to one in applicant's embodiment preferred or the configuration.
| My god | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Compositions | A | A | A | A | A | A | A |
| My god | 8 | 9 | 10 | 11 | 12 | 13 | 14 |
| Compositions | A | A | A | B | B | B | B |
| My god | 15 | 16 | 17 | 18 | 19 | 20 | 21 |
| Compositions | B | B | B | B | B | B | B |
| My god | 22 | 23 | 24 | 25 | 26 | 27 | 28 |
| Compositions | B | B | B | B | B | B | B |
| My god | 29 | 30 | 31 | 32 | 33 | 34 | 35 |
| Compositions | C | C | C | C | C | C | C |
| My god | 36 | 37 | 38 | 39 | 40 | 41 | 42 |
| Compositions | C | C | C | C | C | C | C |
| My god | 43 | 44 | 45 | 46 | 47 | 48 | 49 |
| Compositions | C | C | C | C | C | C | C |
| My god | 50 | 51 | 52 | 53 | 54 | 55 | 56 |
| Compositions | C | C | C | E | E | P | P |
The 1st day is hemorrhage first day.
A=1.0 milligram norethindrone acetate and 10 microgram ethinylestradiols
B=1.0 milligram norethindrone acetate and 20 microgram ethinylestradiols
C=1.0 milligram norethindrone acetate and 30 microgram ethinylestradiols
E=15 microgram ethinylestradiol
The P=placebo
[0040] in another embodiment of table 1, the ethinylestradiol among the A is 5 micrograms, and the ethinylestradiol among the B is 10 micrograms, and the ethinylestradiol among the C is 15 micrograms, and the ethinylestradiol among the E is 5 micrograms.
[0041] should be noted in the discussion above that this form is only used for purpose of explanation.For example, the described cycle of table 1 can be carried out following modification: use only placebo replacement in whole 4 days of Phase IV, and do not use any estrogen.Can consider in these schemes, to carry out the function equivalence amount of medicament and the replacement of kind.For example, can be scheduled to use sugar or all or part of ferrous fumarate of other placebo in place.
[0042] compositions of the present invention can be with suitable dosage form every day, most preferably peroral dosage form is used.Representational dosage form is tablet, pill, capsule and ingot.In addition, also can consider to use other conventional additives, for example filler, coloring agent, polymeric binder or the like.Usually, any pharmacy acceptable additive that can the interferon activity component function may be used to one or more above-mentioned compositionss.
[0043] and the suitable carrier used together of compositions comprise lactose, starch, cellulose derivative of appropriate amount or the like.Lactose is preferred carrier.The mixture of carrier also is feasible.
[0044] term herein " method " and " medicine box " comprise by using 4 above-mentioned phase scheme can be applied to any drug delivery of women effectively.Also can consider to use the combination of different dosage form.
[0045] multistage compositions of the present invention and contraceptive medicine box are a kind of packings, and it comprises Phase I, II and III compositions and the optional but preferred Phase IV composition of the daily dose that is used to implement the inventive method.The dissimilar packing of storing contraceptive is well-known, can consider these packings arbitrarily are used for or change after be used to implement the present invention.For example, prolongation cycle package of the present invention preferably comprises the Phase I composition of about 14 dosage of about 7-; The Phase compositions of about 22 dosage of about 14-; Phase I compositions with about 31 dosage of about 20-.In a preferred embodiment that prolongs cycle package, also comprise the Phase IV composition of about 8 dosage of about 2-.In another embodiment, this packing can comprise the estrogen of about 8 dosage of about 2-of Phase IV, in an amount equivalent to the ethinylestradiol of the about 20mcg of about 5-, and placebo or on-steroidal component.
[0046] though the present invention is described with above-mentioned special embodiment, apparently, can carries out many changes, correction and change, and not break away from notion disclosed in this invention.Therefore, the present invention's requirement also comprises spirit and interior change, correction and the change of broad scope that all these fall into claims.All patent applications of quoting in this article, patent and other publications all integral body are incorporated herein by reference.
Claims (28)
1. multistage contraceptive device, comprise jenny to reproduction age use the step of following compositions continuously:
(a) Phase I composition comprises progestogen, in an amount equivalent to the about 1.5mg norethindrone acetate of about 0.3-; And estrogen, in an amount equivalent to the about 15mcg ethinylestradiol of about 5-, used about 7-about 14 days;
(b) the Phase compositions comprises progestogen, in an amount equivalent to the about 1.5mg norethindrone acetate of about 0.3-; And estrogen, in an amount equivalent to the about 25mcg ethinylestradiol of about 10-, used about 14-about 22 days;
(c) Phase I compositions comprises progestogen, in an amount equivalent to the about 1.5mg norethindrone acetate of about 0.3-; And estrogen, in an amount equivalent to the about 35mcg ethinylestradiol of about 15-, used about 20-about 31 days; With
(d) Ren Xuan Phase IV composition comprises:
I. estrogen, in an amount equivalent to the about 20mcg ethinylestradiol of about 5-, or
Ii. placebo or on-steroidal component, or
The combination of iii.i and ii,
Used about 2-about 8 days,
Wherein in each stage of continuous stages II and III estrogenic ethinylestradiol equivalent proportion at adjacent estrogenic ethinylestradiol equivalent in last stage 5mcg greatly at least.
2. the process of claim 1 wherein that the compositions continuous administration of Phase I, II, III and IV continues about 58 days of about 54-so that the contraceptive cycle of prolongation to be provided.
3. claim 2 method, wherein Phase I composition was used 10 days, and the Phase compositions was used 18 days, and Phase I compositions was used 24 days, and Phase IV composition was used 4 days.
4. the process of claim 1 wherein that Phase IV composition comprises 4 days placebo or on-steroidal component.
5. the process of claim 1 wherein that Phase IV composition comprises 4 days estrogen, in an amount equivalent to the ethinylestradiol of about 15mcg.
6. the process of claim 1 wherein that Phase IV composition comprises 2 days estrogen, in an amount equivalent to the ethinylestradiol of about 15mcg; Placebo or on-steroidal component with 2 days.
7. the process of claim 1 wherein that described on-steroidal based composition comprises ferrous fumarate.
8. claim 1 method, wherein in Phase I, the amount of progestogen keeps constant in II and the III compositions.
9. the process of claim 1 wherein that in Phase I the norethindrone acetate equivalent of progestogen is norethindrone acetates of about 1mg in II and the III compositions.
10. the method for claim 1, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 10mcg in Phase I composition wherein, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 20mcg in the Phase compositions, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 30mcg in Phase I compositions, estrogenic ethinylestradiol equivalent is about 15mcg ethinylestradiol in Phase IV composition.
11. the method for claim 1, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 10mcg in Phase I composition wherein, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 20mcg in the Phase compositions, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 30mcg in Phase I compositions.
12. a multistage contraceptive device, comprise jenny to reproduction age carry out following step continuously:
(a) Phase I composition comprises progestogen, in an amount equivalent to the 1.0mg norethindrone acetate; And estrogen, in an amount equivalent to the 10mcg ethinylestradiol, used 10 days;
(b) the Phase compositions comprises progestogen, in an amount equivalent to the 1.0mg norethindrone acetate; And estrogen, in an amount equivalent to the 20mcg ethinylestradiol, used 18 days;
(c) Phase I compositions comprises progestogen, in an amount equivalent to the 1.0mg norethindrone acetate; And estrogen, in an amount equivalent to the 30mcg ethinylestradiol, used 24 days; With
(d) Phase IV composition comprises:
I. estrogen, in an amount equivalent to the about 20mcg ethinylestradiol of about 5-, or
Ii. placebo or on-steroidal component, or
The combination of iii.i and ii,
Used 4 days.
13. the method for claim 12, wherein Phase IV composition comprises estrogen, in an amount equivalent to the ethinylestradiol of 15mcg, uses 4 days.
14. the method for claim 12, wherein Phase IV composition comprises placebo or on-steroidal component, uses 4 days.
15. the method for claim 12, wherein Phase IV composition comprises estrogen, in an amount equivalent to the ethinylestradiol of 15mcg, uses 2 days, comprises placebo or on-steroidal component then, uses 2 days.
16. a multistage makes up and contraceptive medicine box, comprises a packing, wherein comprises:
(a) Phase I composition of about 14 daily doses of about 7-comprises progestogen, in an amount equivalent to the norethindrone acetate of the about 1.5mg of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 15mcg of about 5-;
(b) the Phase compositions of about 22 daily doses of about 14-comprises progestogen, in an amount equivalent to the norethindrone acetate of the about 1.5mg of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 25mcg of about 10-;
(c) the Phase I compositions of about 31 daily doses of about 20-comprises progestogen, in an amount equivalent to the norethindrone acetate of the about 1.5mg of about 0.3-; And estrogen, in an amount equivalent to the ethinylestradiol of the about 35mcg of about 15-; With
(d) Phase IV composition optional, about 8 daily doses of about 2-comprise:
I. estrogen, in an amount equivalent to the ethinylestradiol of the about 20mcg of about 5-, or
Ii. placebo or on-steroidal component, or
The combination of iii.i and ii,
Wherein in each stage of continuous stages II and III estrogenic ethinylestradiol equivalent proportion at adjacent estrogenic ethinylestradiol equivalent in last stage 5mcg greatly at least.
17. the medicine box of claim 16, wherein this medicine box comprises the Phase I composition of about 14 dosage of about 7-; The Phase compositions of about 22 dosage of about 14-; The Phase I compositions of about 31 dosage of about 20-; Phase IV composition with about 8 dosage of about 2-.
18. the medicine box of claim 16, wherein progestogen are selected from norethindrone acetate, drospirenone, trimegestone, norethindrone, levonorgestrel, desogestrel, 3-keto-desogestrel, gestodene, demegestone, dydrogesterone, medrogestone, medroxyprogesterone, and their esters and mixture.
19. the medicine box of claim 18, wherein progestogen are norethindrone acetates.
20. the medicine box of claim 16, wherein estrogen is selected from ethinylestradiol, 17-, conjugated estrogen, mestranol, estrone, and their esters, prodrug and salt.
21. the medicine box of claim 20, wherein estrogen is ethinylestradiol.
22. the medicine box of claim 16, wherein in Phase I, the norethindrone acetate equivalent of progestogen is norethindrone acetates of about 1mg in II and the III compositions.
23. the medicine box of claim 16, wherein estrogenic ethinylestradiol equivalent is about 10mcg ethinylestradiol in Phase I composition, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 20mcg in the Phase compositions, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 30mcg in Phase I compositions, Phase IV composition comprises the ferrous fumarate of about 75mg.
24. the medicine box of claim 23, wherein in Phase I, estrogen and progestogen are respectively ethinylestradiol and norethindrone acetate in II and the III compositions.
25. the medicine box of claim 16, wherein estrogenic ethinylestradiol equivalent is about 10mcg ethinylestradiol in Phase I composition, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 20mcg in the Phase compositions, the ethinylestradiol that estrogenic ethinylestradiol equivalent is about 30mcg in Phase I compositions, Phase IV composition are the ethinylestradiols of about 15mcg.
26. the medicine box of claim 25, wherein in Phase I, estrogen and progestogen are respectively ethinylestradiol and norethindrone acetate in II and the III compositions.
27. the medicine box of claim 16, wherein the Phase IV composition that comprises of this medicine box comprises the estrogen of amount of the ethinylestradiol that is equivalent to about 15mcg of about 8 dosage of about 2-, and the placebo of about 8 dosage of about 2-or on-steroidal component.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US77806706P | 2006-03-02 | 2006-03-02 | |
| US60/778,067 | 2006-03-02 | ||
| US60/792,653 | 2006-04-18 |
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| Publication Number | Publication Date |
|---|---|
| CN101394845A true CN101394845A (en) | 2009-03-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800075523A Pending CN101394845A (en) | 2006-03-02 | 2007-02-09 | Extended cycle multiphasic oral contraceptive method |
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| Country | Link |
|---|---|
| CN (1) | CN101394845A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110548034A (en) * | 2019-07-12 | 2019-12-10 | 广州莎蔓生物科技有限公司 | Pregnancy-blocking medicine |
-
2007
- 2007-02-09 CN CNA2007800075523A patent/CN101394845A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110548034A (en) * | 2019-07-12 | 2019-12-10 | 广州莎蔓生物科技有限公司 | Pregnancy-blocking medicine |
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Application publication date: 20090325 |