CN1500478A - Release delayed solid oral prophylactic or pregnancy stopping pill and its use - Google Patents
Release delayed solid oral prophylactic or pregnancy stopping pill and its use Download PDFInfo
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- CN1500478A CN1500478A CNA021489564A CN02148956A CN1500478A CN 1500478 A CN1500478 A CN 1500478A CN A021489564 A CNA021489564 A CN A021489564A CN 02148956 A CN02148956 A CN 02148956A CN 1500478 A CN1500478 A CN 1500478A
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Abstract
The present invention relates to the preparation form of contraceptive, and is especially one delayed dissolving orally taken solid preparation form of contraceptive or pregnancy terminating medicine. The present invention also relates to the application of the preparation form. The preparation form has one or several layers of coating or is delayed dissolving capsule, and will dissolve for absorption in neutral medium inside intestinal tract, rather than acid medium. The present invention aims at preventing inaccurate medicine dosage caused by vomiting after taking the contraceptive or pregnancy terminating medicine.
Description
Technical field
The present invention relates to a kind of dosage form of contraceptive, refer to a kind of delay Peroral solid dosage form for contraception or the dissolved dosage form of termination of pregnancy medicine especially; The invention still further relates to the application of this delay Peroral solid dosage form for contraception or the dissolved dosage form of termination of pregnancy medicine.
Background technology
Present widely used women has the main medicine of two classes with contraceptive (not comprising external applied contraceptive).One class is estrogenic derivant or its activity or the active analogies of part, as ethinylestradiol, quinestrol, estradiol, ormeloxifene etc.; Another kind of is progestogen or derivatives thereof or its activity or the active analogies of part, as norethindrone, levonorgestrel, megestrol acetate, medroxyprogesterone acetate, desogestrel (Desogestrel), gestodene (Gestodene), mifepristone, 3-ketone desogestrel (3-Keto-desogestrel), vinegar Norgestel oxime (Norgestimate), norgesterone (Dienogest), nomegestrol acetate (Nomegestrol), drospirenone (Drospirenone), trimegestone (Trimegestrone) etc.In actual drug research or clinical use, generally form compound recipe with various dose composition folk prescription or this two classes medicine with various dose, and, formed a series of women and used contraceptive by different drug delivery methods with one of this two classes medicine.
Present normally used drug for termination of pregnancy generally is to adopt anti-progesterone drug and uterus muscle analeptic prostaglandins drug combination.Wherein, employed gestation class medicine comprises mifepristone and the lilopristone that is in different research and development states (Lilopristone), onapristone (Onapristone) etc.; Wherein employed prostaglandins medicine comprises misoprostol, carboprost methylate etc.The more sophisticated concrete clinical protocol of one class of currently used medicine termination of pregnancy generally is that at a high dose or after low dosage is taken mifepristone several times, oral again or vagina uses misoprostol.
That the main adverse reaction of Peroral solid dosage form for contraception thing or termination of pregnancy medicine generally comprises is nauseating, property or long reaction are crossed in vomiting, dizzy, edema, leucorrhoea grow in quantity, opsomenorrhea or menstrual blood volume minimizing or increase, petechial hemorrhage or break-through bleeding, libido change etc.Although the progestogen of the main Peroral solid dosage form for contraception thing that uses and estrogenic content decline significantly at present, all or part of in these untoward reaction still exists with varying strength or different occurrence frequency.In addition, the contraceptive that contains third generation progestogen (as desogestrel, gestodene) may also increase the incidence rate that causes the deep venous thrombosis.
The soak time of Peroral solid dosage form for contraception thing and termination of pregnancy medicine depends on the bioavailability with holdup time, pharmaceutical dosage form feature (as release time) and the medicine self of medicine in little intestinal.Peroral solid dosage form for contraception thing and termination of pregnancy medicine reach blood peak concentration of drug (Cmax) in human body time (tmax) was generally 1-3 hour.With document (He Chang-hai et al:Comparativecross-over pharmacokinetic study on two types of postcoital contraceptivetablets containing levonorgestrel.Contraception 1990,41:557-567) is basis, the wherein AUC of two kinds of tablets about taking a slice 0.75mg levonorgestrel data
0-24Be respectively 92.2ng/ml/h and 64.4ng/ml/h; Reach the 4th hour pairing curve-time and area AUC from taking medicine
0-4Then be estimated as 28.7ng/ml/h and 16.3/ng/ml/h respectively corresponding to these two kinds of tablets.The ratio of the curve-time and area in these two kinds of time intervals (is AUC
0-4/ AUC
0-24) then be respectively 31% and 25% corresponding to these two kinds of tablets.This just means that 2/3rds medicine does not enter effectively distribution in the blood as yet at least in addition.Therefore, taking Peroral solid dosage form for contraception and termination of pregnancy medicine after 1-3 hour, still there is the medicine of significant proportion dosage in digestive tract, not to be absorbed as yet.
Table: different pharmaceutical reaches the time (Tmax) of blood medicine peak value
| Medicine | Tmax unit: hour | List of references |
| Quinestrol 3.0mg | ??2～3 | JW Goildzieher:Pharmacology of contraceptive steroids:A brief review.Am J Obstet Gynecol 1989,160:1260-1264, summary |
| Ethinylestradiol 35 μ g-50 μ g-100 μ g | ??～1.5 | The same |
| Norethindrone | ?????2 | ?K?Fotherby：Potency?and?pharmacokinetics ?ofgestagens.Contraception?1990， ?41：533-550 |
| Levonorgestrel 0.075-0.125mg | ????1.0～1.2 | ?W?Kuhnz：Pharmacokinetics?of?the ?contraceptive?steroids?levonorgestrel?and ?gestogene?after?single?and?multiple?oral ?administration?to?women.Am?J?Obstet ?Gynecol?1990.163：2120-2127 |
| Levonorgestrel 0.75mg | ????2.0～2.5 | ?Tremblay?D?et?al：The?pharmacokinetics?of ?750?glevonorgestrel?following ?administration?of?one?single?dose?or?two ?doses?at?12-or?24-h?interval.Contraception ?2001，64：327-331 |
| Levonorgestrel 1.5mg | ????2.5 | ?Johansson?E?et?al：Pharmacokinetic?study ?of?different?dosing?regimens?of ?levonorgestrel?for?emergency?contraception ?in?healthy?women.Human?Reprod?2002， ?17：1472-1476 |
| Desogestrel | ????1.5 | ?Viinikka?L.Radioimmunoassay?of?a?new ?progestagen，ORG2969，and?its?metabolite. ?J?Steroid?Biochem?1978，9：979-982 |
| 3-ketone desogestrel | ????1.5 | ?Jung-Hoffmann?C?et?al：Pharmacokinetics ?and?pharmacodynamics?of?oral ?contraceptive?steroids：Factors?influencing ?steroid?metabolism.Am?J?Obstet?Gynecol ?1990，163：2183-2197 |
| The gestodene | ????0.4～1.9 | Wilde MI et al:Gestodene, A review ofits pharrmacology, efficacy and tolerability in combined contraceptive preparations. Dmgs 1995,50:364-395, summary |
| Vinegar Norgestel oxime | ????1.5 | ?McGuire?JL?et?al：Pharmacologic?and ?pharmacokinetic?characteristics?of ?norgestimate?and?its?metabolites.Am?J ?Obstet?Gynecol?1990，163：2127-2131 |
| The ground norgesterone | ????2 | H Kuhl:Comparative Pharmacology of Newer Progestogens.Drugs 1996, the 51:188-215 summary |
| Nomegestrol acetate | ????4 | ?Ezan?E?et?al：Enzyme?immunoassay?for ?nomegestrol?acetate?in?human?plasma.J ?Steroid?Biochem?Mol?Biol?1993， 46：507-514 |
| Mifepristone | ????1～2 | ?Sarkar?NN：Mifepristone：bioavailability， ?pharmacokinetics?and?use-effctiveness. Eur?J?Obstet?Gynecol?Reprod?Biol?2002， 101：113-20 |
The actual taking dose of Peroral solid dosage form for contraception and termination of pregnancy medicine has direct relation for the effectiveness and the untoward reaction of contraception or termination of pregnancy; When the dosage of especially working as the medicine of being taken was lower than prescribed dose, the effective percentage of contraception or termination of pregnancy can descend.The vomiting that Peroral solid dosage form for contraception and termination of pregnancy medicine are directly caused generally occurs in to take behind the medicine and took place in several hours in a few minutes, and the great majority vomiting occurs in and takes behind the medicine in 30 minutes to 3 hours.During this period of time, still have a large amount of medicines to remain in gastric, if medicine is to take after the meal and do not use a large amount of liquid to take, the medicine that then still may have solid form is present in gastric.Therefore, vomit after taking Peroral solid dosage form for contraception or termination of pregnancy medicine, the medicine that has doses is vomitted.
In the description of part contraceptive or termination of pregnancy medicine, generally point out patient after vomitting, to need to mend the medicine of clothes same dose.But in the actual drug use,, there are following three kinds of situations to take place according to our investigation.
1) because what mend clothes is whole single taking dose, and vomiting lose only be part dosage, thereby cause the actual dosage of taking medicine to increase after mending the thing of taking medicine, increase or the untoward reaction of enhancing part.Such as for containing estrogenic contraceptive, the estrogen dosage of taking is high more, and the kind of the untoward reaction that is produced is more or/and degree is stronger;
2) for various reasons patient do not have requirement to specifications or follow the doctor's advice and mend clothes same dose medicine, thereby cause the actual dosage of taking medicine to be lower than the dosage of requirement, may the last therapeutic effect of medicine be exerted an influence.The reason of mending clothes comprise forget, frightened, take for the loss that do not have medicine etc. because of the nauseating medicine that can't swallow, in vomitus, not find molding (as the complete and remaining tablet of disintegrate not as yet);
3) patient's vomiting once more after benefit is taken medicine thing, therefore and produce any in above-mentioned two kinds of situations once more.
On the one hand, in Peroral solid dosage form for contraception and termination of pregnancy adverse effect, the incidence rate of vomiting generally is higher than the mortality of contraception or termination of pregnancy.On the other hand, a certain proportion of patient is arranged really in the patient that vomiting takes place, make the medicine of actual absorption not meet the requirements of dosage because above-mentioned reason is not mended clothes or successfully do not mended the thing of taking medicine.Therefore, in failure case, has the part failure case partly or entirely because the vomiting back is caused.
Preventing or treating in the vomiting that causes because taking the levonorgestrel sheet, in the world some doctor special-purpose medicaments of dosing a patient with and preventing or treat vomiting.Medicine commonly used has the Mei Keluo Qin etc.One group of clinical research finishing recently shows, this class prevents or treats the effective percentage of vomitting medicine and often have only below 70%, and take sleepy ratio double above (reach 31%, the blank group is 13%, and not taking Mei Keluo Qin group is 16%) takes place after the Mei Keluo Qin.(Raymond?EG?et?al：Meclizine?for?prevention?of?nausea?associated?with?use?of?emergencycontraceptive?pills：arandomized?trial.Obstet?Gynecol?2000，95：271-277)。In fact be lower than 25% owing to take the incidence of vomiting of Peroral solid dosage form for contraception or oral termination of pregnancy, and quite a few Peroral solid dosage form for contraception often needs even take every day, and therefore the people that obviously should not allow all take contraceptive or termination of pregnancy medicine all takes the emesis medicine.So this additionally taking prevents that the method for vomitting medicine is not used widely.
This shows,, can cause dosage inaccurate of the medicine taken, and therefore may influence the prevention or the therapeutic effect of medicine because take the vomiting that Peroral solid dosage form for contraception or termination of pregnancy medicine are caused.Additionally take and prevent that the medicine of vomitting from can cause the generation of other more untoward reaction.If can postpone Peroral solid dosage form for contraception or termination of pregnancy medicine at the intravital dissolution time of people, both made and not necessarily reduced incidence of vomiting or/and alleviate vomiting intensity, but can prevent effectively because vomiting and the dosage of the medicine of being taken that causes is higher or lower than desired dosage, and can further alleviate unnecessary painful of patient or improve the prevention or the therapeutic effect of medicine.
Summary of the invention
The object of the present invention is to provide a kind of delay Peroral solid dosage form for contraception or the dissolved dosage form of termination of pregnancy medicine, cause the inaccurate of actual taking dose to prevent when taking Peroral solid dosage form for contraception or termination of pregnancy medicine because of vomiting.
Delay Peroral solid dosage form for contraception of the present invention or the dissolved dosage form of termination of pregnancy medicine are characterised in that, skin at Peroral solid dosage form for contraception or termination of pregnancy medicine preparation is wrapped one or more layers coating, perhaps directly use whole shell structure to have the capsule that postpones dissolution, this dosage form is not dissolved in acid medium, and dissolve near in the neutral medium in acidity.
Delay Peroral solid dosage form for contraception of the present invention or the dissolved dosage form of termination of pregnancy medicine are specifically used the enteric dosage form, be that oral formulations or granule outsourcing at contraceptive of making and termination of pregnancy medicine is coated with the dissolved non-toxic biocompatible material of the special delay of one deck, make tablet or capsule again after perhaps making the microsphere particle that postpones to discharge; The oral formulations that every pharmacy indexs such as its dosage form, dosage, outward appearance, shape, volume, weight, taste, total dissolution are handled with the drug delivery mode of not carrying out any delay release does not have significant change, can change accordingly aspects such as dosage form, dosage, outward appearance, shape, volume, weight, taste, total dissolution, dissolution times according to new requirement yet.
Said coating material comprises: Lac, cellulose acetate class, ethyl cellulose class, carboxymethyl cellulose salt class, cellulose acetate-phthalate, benzenetricarboxylic acid cellulose acetate, hydroxypropylmethyl cellulose phthalate, No. 1,2,3, acrylic resin, polyacrylic resin class, polyvinyl acetate phthalic acid ester, succinic acid hydroxypropylmethylcellulose acetate methylcellulose, crosslinked alginates, and the mixture formed of their wherein two kinds or multiple materials etc.
Delay Peroral solid dosage form for contraception of the present invention or the dissolved dosage form of termination of pregnancy medicine comprise that the capsule, tablet of various dosage, outward appearance, shape, volume, weight, taste or other are suitable for carrying out the solid orally ingestible of coating; Employed oral administration solid contraceptive or termination of pregnancy medicine preparation are for can nauseant Peroral solid dosage form for contraception or termination of pregnancy medicine after taking.Said Peroral solid dosage form for contraception or termination of pregnancy medicated bag are drawn together: estrogenic derivant or its activity or the active analogies of part, estrogenic derivant or its activity or the active analogies of part comprise having the active non-natural compound of estrogen antagonist, and progestogen or derivatives thereof or its activity or the active analogies of part, this progestogen or derivatives thereof or its activity or the active analogies of part comprise the non-natural compound with antiprogestational action.
Peroral solid dosage form for contraception or termination of pregnancy medicated bag that delay Peroral solid dosage form for contraception of the present invention or the dissolved dosage form of termination of pregnancy medicine are used are drawn together: ethinylestradiol, quinestrol, ethinylestradiol ether, estradiol valerate, ring amyl ether Estra-1,3,5(10)-triene-3,17beta-diol 17-propionate, 17 β estradiol, Quingestanol Acetate, ormeloxifene, norethindrone, levonorgestrel, norethisterone oenanthate, norethindrone acetate, norethindrone-3-oxime, NaOH, Norethynodrel, Orgametrol, ethynodiol diacetate, norgestrel, norgestrienone, megestrol acetate, medroxyprogesterone acetate, chlormadinone acetate, the acetic acid methylenechlormadinoni acetas, medroxyprogesterone, delalutin, cyproterone, desogestrel, the gestodene, 3-ketone desogestrel, vinegar Norgestel oxime, the ground norgesterone, the acetic acid nomegestrol, drospirenone, mifepristone, lilopristone, onapristone, and their compound preparation etc.
The actual dose that is wrapped in these medicines in the delayed release coating can be the consumption before not using the present invention, also can be other dosage.Being wrapped in the dosage form that postpone to discharge in the thin film is based on solid orally ingestible, the granule that comprises tablet (such as multilayer tablet), different shape and the size capsule agent of the tablet of granule, suspensoid, different shape and size or various composite constructions or make different shape and all size in advance forms capsule then, make make again behind the microsphere particle that postpones release tablet or capsule, or the like.Being wrapped in these medicines that postpone to discharge in the thin film can be folk prescription, also can be the compound recipe that two or more these ingredients are formed, the compound recipe that can also form by other one or more medicines outside the medicine of one or more compositions in these medicines and indication of the present invention.Its compound recipe composition mode is to mix the back granulation with each active component to make solid preparation again, or employed whole active component back of granulating respectively mixed and to make solid preparation again, or the different activities composition is made solid preparation (as tablet) back making compound formulation (as the MULTILAYER COMPOSITE preparation).The basic dosage form that is wrapped in the delayed release coating can be simple peroral dosage form, also can be other slow release or controlled release form.
Delay Peroral solid dosage form for contraception of the present invention or the dissolved dosage form of termination of pregnancy medicine can be applied in Peroral solid dosage form for contraception or the termination of pregnancy medicine, its concrete application purpose is medicine insoluble or slightly soluble in acid (being lower than 3 as pH) medium, but then increase substantially near disintegrate and stripping in neutral (as pH greater than 5), and within the specific limits along with the also corresponding raising of its disintegration rate of raising, dissolution rate and dissolution rate of acidity in acidity.This medicine that postpones dissolve dosage form is insoluble under one's belt, but after entering intestinal, then begin disintegrate, stripping and be absorbed, reduced because the inherent feature of medicine caused vomiting and dosage inaccurate that may cause the medicine of taking, and reduced because of vomiting and need the take medicine probability of thing of benefit.
Among the present invention the delay dissolve dosage form of Peroral solid dosage form for contraception or termination of pregnancy medicine release time length definite principle be: do not dissolve at gastric (pH is about 1 sour environment), (pH progressively rise near neutral) then begins dissolving and absorbs after entering small intestinal.The time that postpones to discharge generally is meant from 15 minutes to 5 hours, effect with 1-3 hour serves as better, optimum efficiency should be according to the purpose of employed concrete medicine, drug use, time and the employed prescription that needs postpone release, and concrete screening is determined according to actual experiment result from external to intravital.
Show through experiment in vitro,, under certain prescription condition, make delay dissolve dosage form (capsule or tablet) the representative type medicine of each class in the said medicine.Disintegrate or dissolving did not take place in all delayed dosage forms in 2 hours in pH is 1 acid medium; In the nearly neutral medium of pH6.8, stripping all reaches more than 75% in 60 minutes.
Show through the experiment of animal, the delay dissolve dosage form of this class medicine, except that the inherent untoward reaction of pairing active pharmaceutical ingredient, no oncogenic function, no teratogenesis, do not have other untoward reaction at no mutagenic action.Postpone in the process of dissolve dosage form in preparation, that employed all material is is highly stable, inertia and to animals and human beings height degree safety.Therefore, the delay dissolve dosage form of this class medicine is a high safety.
Further illustrate the content of patent of the present invention below by specific embodiment.But should be appreciated that the content of patent of the present invention and the content that claimed scope includes, but are not limited to following example.
The specific embodiment
Embodiment 1:
With 0.75g or 1.50g levonorgestrel and 80g lactose, 5g polyvinylpyrrolidone, 10g sodium carboxymethyl cellulose, 20g starch, and the abundant mixing of powdery adjuvant such as 50 g microcrystalline Cellulose, granulate with water, the circular tablet that it is 8mm that oven dry is pressed into 1000 diameters behind the granulate, the content of every middle levonorgestrel is 0.75mg or 1.50mg.Simultaneously, the ethanol with 88% is as solvent, and the special-purpose coating material that will contain cellulose acetate-phthalate is mixed with 10～15% solid suspensions, behind the mixing, coats multilamellar outside the tablet of making.Made coated tablet stirred 2 hours in the hydrochloric acid (pH is 1) of the 0.1N of 750ml, was not more than 10% without any disintegrate or stripping.(HCl/NaOH with 1N regulates pH value to 6.8 in the sodium radio-phosphate,P-32 solution of 0.2N; The sodium lauryl sulphate that adds 5g), disintegrate took place about 10 minutes in made coated tablet and wherein stirring, and the sampling and measuring dissolution rate is more than or equal to 75% after 1 hour.
Embodiment 2:
With the acrylic resin soln that configures, outside No. 3 capsules, shoot out this resin of last layer; Or directly buy to obtain No. 3 capsules of enteric solubility of state approval.With 10g mifepristone and 70g lactose, 10g polyvinylpyrrolidone, 8g sodium carboxymethyl cellulose, and the abundant mixing of powdery adjuvant such as 2g magnesium stearate, granulate with water, oven dry is recorded into behind the granulate in 1000 No. 3 capsules of above-mentioned coating, and the content of mifepristone is 10mg in every capsules.Made coating capsule stirred 2 hours in the hydrochloric acid (pH is 1) of the 0.1N of 750ml, during without any breaking or being out of shape.At pH is in the sodium radio-phosphate,P-32 solution of 6.8 0.2N, and made coating capsule breaks about 15 minutes through stirring, and thoroughly discharges the medicament capsule inclusions about 30 minutes, and the sampling and measuring dissolution rate is more than or equal to 78% after 1 hour.
Embodiment 3:
70 gram carboxymethyl celluloses are dissolved in boiling water, be cooled to room temperature, add the 25g mifepristone and make the suspendible aqueous solution, slowly add aluminum sulfate aqueous solution and at the uniform velocity stirring then, until the cohesion capsule thing that forms saturation, filter after washing and remove soluble substance, the dry then microsphere particle that forms, average diameter of particles is 0.4mm.After microsphere carried out the cellulose acetate-phthalate coating, record in 1000 No. 3 conventional capsules, the content of mifepristone is 25mg in every capsules, and the content of mifepristone is 250mg in every gram microsphere particle.Dissolving took place and discharges microsphere particle in capsule when made capsule stirred 15 minutes in the hydrochloric acid (pH is 1) of the 0.1N of 750ml, continue to be stirred to 2 hours, all granules discharge from capsule fully, but microsphere particle do not take place anyly to break or dissolve, and dissolution is not more than 10%.At pH is in the sodium radio-phosphate,P-32 solution of 6.8 0.2N, and made coating capsule breaks about 15 minutes through stirring, and the sampling and measuring dissolution rate is more than or equal to 70% after 1 hour.
Embodiment 4:
With 0.15g levonorgestrel and 0.03g quinestrol and 80g lactose, 5g polyvinylpyrrolidone, 10g sodium carboxymethyl cellulose, 20g starch, and the abundant mixing of powdery adjuvant such as 50 g microcrystalline Cellulose, granulate with water, the circular tablet that it is 8mm that oven dry is pressed into 1000 diameters behind the granulate contains the levonorgestrel of 0.15mg and the quinestrol of 0.03mg in every.Simultaneously, the ethanol with 85% is as solvent, and will contain the special-purpose coating material of cellulose acetate-phthalate and be mixed with 10～15% suspension, behind the mixing, the tablet outsourcing last layer of making.Made coated tablet stirred 2 hours in the hydrochloric acid (pH is 1) of the 0.1N of 750ml, was not more than 10% without any disintegrate or stripping.(HCl/NaOH with 1N regulates pH value to 6.8 in the sodium radio-phosphate,P-32 solution of 0.2N; The sodium lauryl sulphate that adds 5g), made coated tablet with wherein stir, about 10 minutes disintegrate complete, the dissolution rate of sampling and measuring levonorgestrel and quinestrol is respectively more than or equal to 75% and 80% after 1 hour.
Claims (14)
1. one kind postpones Peroral solid dosage form for contraception or the dissolved dosage form of termination of pregnancy medicine, it is characterized in that, wrap one deck or multiple coatings or have certain thickness layer structure at the skin of oral administration solid contraceptive or termination of pregnancy medicine preparation, this dosage form is not dissolved in acid medium, and dissolve near in the neutral medium in acidity.
2. delay Peroral solid dosage form for contraception according to claim 1 or the dissolved dosage form of termination of pregnancy medicine, it is characterized in that said coating material comprises: Lac, the cellulose acetate class, the ethyl cellulose class, the carboxymethyl cellulose salt class, cellulose acetate-phthalate, the benzenetricarboxylic acid cellulose acetate, hydroxypropylmethyl cellulose phthalate, acrylic resin 1,2, No. 3, the polyacrylic resin class, the polyvinyl acetate phthalic acid ester, succinic acid hydroxypropylmethylcellulose acetate methylcellulose, crosslinked alginates, and by two or more mixture formed in the above-mentioned material.
3. delay Peroral solid dosage form for contraception according to claim 1 or the dissolved dosage form of termination of pregnancy medicine is characterized in that, said have certain thickness layer structure and comprise: capsular housing itself has the dissolved effect of delay.
4. delay Peroral solid dosage form for contraception according to claim 1 or the dissolved dosage form of termination of pregnancy medicine is characterized in that, said dosage form comprises based on the oral formulations of capsule, tablet, microsphere or is suitable for carrying out the solid orally ingestible of coating.
5. delay Peroral solid dosage form for contraception according to claim 1 or the dissolved dosage form of termination of pregnancy medicine, it is characterized in that employed oral administration solid contraceptive or termination of pregnancy medicine preparation are for can nauseant Peroral solid dosage form for contraception or termination of pregnancy medicine after taking.
6. according to described delay Peroral solid dosage form for contraception of claim 5 or the dissolved dosage form of termination of pregnancy medicine, it is characterized in that, said Peroral solid dosage form for contraception or termination of pregnancy medicated bag are drawn together: estrogenic derivant or its activity or the active analogies of part, and progestogen or derivatives thereof or its activity or the active analogies of part.
7. delay Peroral solid dosage form for contraception according to claim 6 or the dissolved dosage form of termination of pregnancy medicine is characterized in that, said estrogenic derivant or its activity or the active analogies of part comprise having the active non-natural compound of estrogen antagonist.
8. according to described delay Peroral solid dosage form for contraception of claim 6 or the dissolved dosage form of termination of pregnancy medicine, it is characterized in that said progestogen or derivatives thereof or its activity or the active analogies of part comprise the non-natural compound with antiprogestational action.
9. according to described delay Peroral solid dosage form for contraception of claim 5 or the dissolved dosage form of termination of pregnancy medicine, it is characterized in that, said Peroral solid dosage form for contraception or termination of pregnancy medicated bag are drawn together ethinylestradiol, quinestrol, ethinylestradiol ether, estradiol valerate, ring amyl ether Estra-1,3,5(10)-triene-3,17beta-diol 17-propionate, 17 β estradiol, Quingestanol Acetate, ormeloxifene, norethindrone, levonorgestrel, norethisterone oenanthate, norethindrone acetate, norethindrone-3-oxime, NaOH, Norethynodrel, Orgametrol, ethynodiol diacetate, norgestrel, norgestrienone, megestrol acetate, medroxyprogesterone acetate, chlormadinone acetate, the acetic acid methylenechlormadinoni acetas, medroxyprogesterone, delalutin, cyproterone, desogestrel, the gestodene, 3-ketone desogestrel, vinegar Norgestel oxime, the ground norgesterone, the acetic acid nomegestrol, drospirenone, mifepristone, lilopristone, onapristone, and the compound preparation of these medicines etc.
10. according to each described delay Peroral solid dosage form for contraception of claim 1-9 or the dissolved dosage form of termination of pregnancy medicine, it is characterized in that this dosage form is to contain the folk prescription solid orally ingestible of a kind of medicine as active component.
11., it is characterized in that this dosage form is to contain the compound solid oral formulations of multiple medicine as active component according to each described delay Peroral solid dosage form for contraception of claim 1-9 or the dissolved dosage form of termination of pregnancy medicine.
12. delay Peroral solid dosage form for contraception according to claim 11 or the dissolved dosage form of termination of pregnancy medicine, it is characterized in that, its compound recipe composition mode is to mix the back granulation with each active component to make solid preparation again, or employed whole active component back of granulating respectively mixed and to make solid preparation again, or make compound formulation (as the MULTILAYER COMPOSITE preparation) again after the different activities composition made solid preparation (as tablet), or directly make and make tablet or capsule again after postponing to discharge microsphere particle.
13. each described delay Peroral solid dosage form for contraception of claim 1-9 or the application of the dissolved dosage form of termination of pregnancy medicine in Peroral solid dosage form for contraception or termination of pregnancy medicine.
14. application according to claim 13 is characterized in that, this delay Peroral solid dosage form for contraception or the dissolved dosage form of termination of pregnancy medicine are insoluble under one's belt, but begin disintegrate after entering intestinal, dissolve and be absorbed.
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| CNB021489564A CN100540008C (en) | 2002-11-14 | 2002-11-14 | Postpone Peroral solid dosage form for contraception or dissolved dosage form of termination of pregnancy medicine and application thereof |
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| CNB021489564A CN100540008C (en) | 2002-11-14 | 2002-11-14 | Postpone Peroral solid dosage form for contraception or dissolved dosage form of termination of pregnancy medicine and application thereof |
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| CN100540008C CN100540008C (en) | 2009-09-16 |
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| CN103610660A (en) * | 2013-12-16 | 2014-03-05 | 北京元延医药科技有限公司 | Enteric coated tablet as hormone medicine |
| CN103877058A (en) * | 2014-03-26 | 2014-06-25 | 邵娜 | Levonorgestrel tablet and preparation process thereof |
| CN109820859A (en) * | 2019-04-09 | 2019-05-31 | 上海市计划生育科学研究所 | The application in cachectic drug is vomitted or improved to nomegestrol acetate in preparation prevention or treatment |
| CN110917154A (en) * | 2019-12-12 | 2020-03-27 | 上海信谊天平药业有限公司 | Preparation method of levonorgestrel tablets |
| JP2020193229A (en) * | 2019-02-13 | 2020-12-03 | 富士製薬工業株式会社 | Oral solid composition, production method thereof, and oral tablet obtained by the production method |
| CN114376990A (en) * | 2022-01-21 | 2022-04-22 | 深圳市资福药业有限公司 | Mifepristone capsule and preparation method thereof |
-
2002
- 2002-11-14 CN CNB021489564A patent/CN100540008C/en not_active Expired - Lifetime
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101596172A (en) * | 2009-07-03 | 2009-12-09 | 北京华禧联合科技发展有限公司 | Oral agents of a kind of energy dosing fertility-controlling drugs by positioning at small intestine and preparation method thereof |
| CN102048681A (en) * | 2010-12-20 | 2011-05-11 | 广州共禾医药科技有限公司 | Mifepristone slow release preparation characterized by gastric stasis and preparation method thereof |
| CN102113494A (en) * | 2011-01-10 | 2011-07-06 | 广东省昆虫研究所 | Rat sterility bait for inhibiting reproduction of female rats |
| CN103610660A (en) * | 2013-12-16 | 2014-03-05 | 北京元延医药科技有限公司 | Enteric coated tablet as hormone medicine |
| CN103877058A (en) * | 2014-03-26 | 2014-06-25 | 邵娜 | Levonorgestrel tablet and preparation process thereof |
| JP2020193229A (en) * | 2019-02-13 | 2020-12-03 | 富士製薬工業株式会社 | Oral solid composition, production method thereof, and oral tablet obtained by the production method |
| CN109820859A (en) * | 2019-04-09 | 2019-05-31 | 上海市计划生育科学研究所 | The application in cachectic drug is vomitted or improved to nomegestrol acetate in preparation prevention or treatment |
| CN110917154A (en) * | 2019-12-12 | 2020-03-27 | 上海信谊天平药业有限公司 | Preparation method of levonorgestrel tablets |
| CN114376990A (en) * | 2022-01-21 | 2022-04-22 | 深圳市资福药业有限公司 | Mifepristone capsule and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN100540008C (en) | 2009-09-16 |
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