CN1899643A - Pessary or intrauterine medicine release device containing antiestrogenic and anti-pregnant hormone composite preparation and its use - Google Patents
Pessary or intrauterine medicine release device containing antiestrogenic and anti-pregnant hormone composite preparation and its use Download PDFInfo
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- CN1899643A CN1899643A CN 200510027902 CN200510027902A CN1899643A CN 1899643 A CN1899643 A CN 1899643A CN 200510027902 CN200510027902 CN 200510027902 CN 200510027902 A CN200510027902 A CN 200510027902A CN 1899643 A CN1899643 A CN 1899643A
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Abstract
The present invention is a kind of pessary or intrauterine medicine releasing device containing one medicine part, and features the medicine part containing anti-estrogen in 40-70 weight portions and anti-progestogen in 30-60 weight portions. The present invention also provides the application of the pessary or the intrauterine medicine releasing device in preparing medicine for treating hysteromyma or endometriosis.
Description
(1) technical field
The present invention relates to contain the pessary of estrogen antagonist and gestation compound formulation or in utero medicament release device and their application in pharmacy thereof.
(2) background technology
Hysteromyoma at present heals with medicine, endometriosis, the trial of many effective explorations has been arranged clinically, often adopt systemic administrations such as oral or injection, but most patient can't be finished the treatment cycle of drug effect reward because systemic administration dosage is big, and the side reaction of its medicine causes patient to be difficult to adhere to for a long time medication, finally fail in a great undertaking on the verge of success, do not reach the purpose of treatment hysteromyoma.
Tentatively relate in the application number that the applicant proposed April 21 calendar year 2001 is 01112712.0 Chinese patent application and contain the pessary that is selected from a kind of or at least a medicine in mifepristone, danazol, Progesterone, Reynolds former times phenol (Raloxifene), tamoxifen (Tamoxifene), the NSC-70735 (Nafoxidine), this provides a kind of lasting, constant, high zero-order release system of measuring.
The LNG-IUD (levonorgestrel intrauterine device) that has gone on the market at present is the in utero release birth control apparatus that Finland Li Lasi pharmaceutical factory produces, and it is made up of interior plasticity support, cylinder type pastille layer of silica gel and silica gel controlled release layer.The applicant has proposed this in utero a kind of preparation method of medicine-feeder in 03116814.0 patent application of its submission.
The present technique field presses for the compound recipe drug delivery system that synergism is strong, curative effect is clear and definite, and the applicant develops and contains the medicament release device with synergistic medicine based on the above-mentioned pessary technology and the technology of medicament release device in utero.
(3) summary of the invention
An object of the present invention is to provide a kind of pessary or intrauterine medicament release device that comprise with synergistic estrogen antagonist and gestation compound formulation.
A further object of the present invention provides above-mentioned pessary or the in utero application of medicament release device in pharmacy.
First aspect present invention provides a kind of pessary, and it comprises pastille part and the silastic-layer that is coated on the pastille part; Described pastille partly comprises, by pastille part gross weight, and 5-70 weight active medicine, the physiology of acceptable surfactant and surplus goes up acceptable dispersant on the 0.5-20 weight % physiology.The described thickness that is coated on the silastic-layer on the pastille part is the 0.01-0.5 millimeter; It is characterized in that in described active medicine, by 100 weight portion active medicines, antiestrogen is the 40-70 weight portion, onapristone is the 30-60 weight portion.
Wherein said antiestrogen is selected from Reynolds former times phenol (Raloxifene), tamoxifen (Tamoxifene), NSC-70735 (Nafoxidine) or aromatase inhibitor (Arometase Inhibitor), and described aromatase inhibitor preferably is selected from Anna's Si azoles (Anastrozole), Ai Simeitan (Exemestane) and letrozole (Letrzol); Described onapristone is selected from mifepristone or gestrinone.
Preferred active medicine mix proportion scheme is that the mifepristone of 60% weight is mixed with the letrozole of 40% weight.
The last acceptable surfactant of described physiology preferably is selected from one or more surfactant mixtures in span 20-80, brejs (Brij) 52-76, OP emulsifying agent, PEG 400-20000, pluronic-124 (molecular weight 2090-2360), pluronic-188 (molecular weight 7680-9510), sodium lauryl sulphate, sodium tetradecyl sulfate, dodecyl sodium sulfate and the triethanolamine.
Described physiology goes up the mixture that acceptable dispersant is selected from one or more dispersants in glycerol, propylene glycol, PEG 400-20000, succinic acid, cholic acid, deoxycholic acid, hexadecanol, octadecanol, β type cyclodextrin (molecular weight 1134), γ type cyclodextrin (molecular weight 1084-2015) and the silicone rubber.When one of surfactant is PEG class or pluronic time-like, selected dispersant then is the material that is different from surfactant.
Described silicone rubber can be HTV (high temperature vulcanized or heat cure, molecular weight 30-100 ten thousand), RTV-2 (double component room temperature vulcanization, molecular weight 0.74-11 ten thousand), RTV-1 is (single-component room temperature vulcanized, molecular weight 0.74-11 ten thousand) or LTV (baking, molecular weight 400-20000), Dow corning silastic-382 medical grade silicone rubber, Dow corning Q7 medical grade silicone rubber series and Dow corning implant the level MDX series or the medical grade silicon rubber of respective series.
The silastic-layer that is coated on the pastille part is selected from HTV (high temperature vulcanized or heat cure, molecular weight 30-100 ten thousand), RTV-2 (double component room temperature vulcanization, molecular weight 0.74-11 ten thousand), RTV-1 is (single-component room temperature vulcanized, molecular weight 0.74-11 ten thousand) or LTV (baking, molecular weight 400-20000), Dow corning silastic-382 medical grade silicone rubber, Dow corning Q7 medical grade silicone rubber series and Dow corning implant the level MDX series or the medical grade silicon rubber of respective series.
In one embodiment of the invention, the pastille part, first medicated layer that preferably contains estrogen antagonist or gestation partly is positioned at the center of pessary, in coat in the heart and contain gestation or antiestrogenic second medicated layer, be silicone rubber coating on every side.
In another embodiment of the invention, the center of pessary comprises the hollow parts that is surrounded by internal lining pipe, and the pastille part is between internal lining pipe and silicone rubber coating.Described internal lining pipe can be made of above-mentioned medical grade silicon rubber and other medical high polymer polymer.
In another embodiment of the present invention, the center of pessary comprises the medical grade silicon rubber post, described pastille part, preferably contain first medicated layer part of estrogen antagonist or gestation and contain gestation or the antiestrogenic second medicated layer part, be coated on the medical grade rubber post, on second medicated layer, coat silastic-layer again.
In all embodiments, the silastic-layer thickness that is coated on the pastille part is the 0.02-1 millimeter.
Second portion of the present invention provides a kind of intrauterine medicament release device, comprise medicine-feeder (IUD) support in utero, be coated on the support first medicated layer and in second medicated layer on first medicated layer and be coated on controlled release layer on second medicated layer, described first medicated layer and second medicated layer are formed by the silicone of active medicine that is independently selected from antiestrogen and onapristone and medical grade or the high molecular polymer mixed by 1-70: 99-30, condition is when first medicated layer contains estrogen antagonist, and second medicated layer then contains gestation; Perhaps, when first medicated layer contained gestation, second medicated layer then contained estrogen antagonist, it is characterized in that, in described active medicine, by 100 weight portion active medicines, antiestrogen is the 40-70 weight portion, and onapristone is the 30-60 weight portion.
Third part of the present invention provides a kind of in utero medicament release device, comprise in utero medicine-feeder (IUD) support, be coated on and contain the lobe layer on the support and be coated on the controlled release layer that contains on the lobe layer, the described lobe layer that contains is formed by the silicone of active medicine and medical grade or the high molecular polymer mixed by 1-70: 99-30, it is characterized in that, in described active medicine, by 100 weight portion active medicines, antiestrogen is the 40-70 weight portion, and onapristone is the 30-60 weight portion.
Wherein said antiestrogen is selected from Reynolds former times phenol (Raloxifene), tamoxifen (Tamoxifene), NSC-70735 (Nafoxidine) or aromatase inhibitor (Arometase Inhibitor), and described aromatase inhibitor preferably is selected from Anna's Si azoles (Anastrozole), Ai Simeitan (Exemestane) and letrozole (Letrzol); Described onapristone is selected from mifepristone or gestrinone.
The mifepristone that preferred active medicine mix proportion scheme is 60% weight mixes with the letrozole of 40% weight.
Described in utero medicine-feeder (IUD) support is that T type, Y type, umbellate form or other have the liner non-toxic polyvinyl chloride support or the silicone rubber support of the various skeletons of similar trailing arm type.
Each in utero the active medicine content in the medicament release device be 30mg-200mg, preferably 10-50mg.
Described release-controlled film is made up of silicone or medical high polymer polymer, and its thickness is 0.01-0.5mm, preferably 0.05-0.5mm.
Another aspect of the present invention provides described pessary or the in utero application of medicament release device in preparation treatment hysteromyoma medicine or endometriosis medicine.
Description of drawings
Fig. 1 is the sketch map of pessary of the present invention.
Fig. 2 a is the profile of one embodiment of the invention medial vagina ring.
Fig. 2 b is the profile of another embodiment of the invention medial vagina ring.
Fig. 2 c is the profile of another embodiment medial vagina ring of the present invention.
Fig. 3-1,3-2,3-3 are the sectional views of drug layer valva in the in utero medicament release device of third aspect present invention.
Fig. 4 is the sketch map of drug layer valva in the in utero medicament release device of third aspect present invention, and wherein 1 for containing lobe, and 2 is the mould metal bar.
Fig. 5 is the sketch map of in utero medicament release device of the present invention, and wherein 1 is IUD plasticity support, and 2 is medicated layer, and 3 is controlled release layer.
Below in conjunction with accompanying drawing the present invention is set forth.
Fig. 1 is the sketch map of pessary of the present invention, and the diameter of pessary can be 1-10 centimetre, now along the a-a direction pessary is intercepted, and makes profile 2a and 2b that signal pessary of the present invention constitutes.
Among Fig. 2 a, dash area 1 refers to the pastille part, and 2 refer to silicone rubber coating, and wherein silicone rubber coating thickness is 0.02-1mm.
Among Fig. 2 b, dash area 1 refers to the pastille part, and 2 refer to silicone rubber coating, and 3 refer to internal lining pipe.Internal lining pipe is the pipe that is made of medical grade silicon rubber or other medical high polymer polymer, it has surrounded pessary hollow core part 4, the diameter of hollow parts 4 can be 2.5-6.5cm, internal lining pipe thickness is 1-6mm, the gross thickness of first and second medicated layer is 0.5-3mm, and silicone rubber coating thickness is the 0.02-1 millimeter.
Among Fig. 2 c, dash area 1 refers to the pastille part, and 2 refer to silicone rubber coating, and round dot part 5 refers to the medical grade silicon rubber post, and the diameter of described medical grade silicon rubber post is 3-8 centimetre, and medicated layer thickness is the 0.5-3 millimeter, and silicone rubber coating thickness is the 0.02-1 millimeter.
The preparation technology of pessary of the present invention mainly adopts injection vulcanization forming well known in the art, molded vulcanization molding, extrudes sulfidization molding, impregnating technology, comprises the following steps: specifically
A. partly form by aforesaid pastille and prepare the pastille part, the pastille of being prepared is partly put into foaming medical grade silicon rubber pipe, put into mould, hot-forming; Perhaps
B. (1) is squeezed into the solid post of required size, i.e. medical grade rubber post with medical grade silicon rubber;
(2) partly form preparation according to pastille as herein described, be pressed into thin skin after this formulation is mixed;
(3) thin skin that (2) step is obtained is coated on the medical grade silicon rubber post that (1) obtain;
(4) coat the medical grade silicon rubber of one deck 0.02-1mm on the product that obtains in (3) again; Perhaps
C. (1) chooses the internal lining pipe that is made of medical grade silicon rubber or other medical polymer material that diameter is the 1-6 millimeter, surrounds diameter and be 2.5-6.5 centimetre hollow parts;
(2) partly form preparation according to pastille as herein described, be pressed into thin skin after this formulation is mixed;
(3) thin skin that (2) step is obtained is coated on the internal lining pipe that has hollow parts that (1) obtain;
(4) coat the medical grade silicon rubber of one deck 0.02-1mm on the product that obtains in (3) again; Perhaps
D. silicone rubber is added an amount of organic solvent, in petroleum ether, mixing, the product that B (3) or C (3) are obtained is immersed in this impregnation liquid then, takes out after 5 seconds and dries.
The in utero medicament release device of second aspect present invention obtains by following prepared:
1. the first medicated layer component that will contain estrogen antagonist or gestation and medical grade silicone or high molecular polymer directly is coated on the polyethylene IUD plasticity support of T type or r type structure with mould, and then stack contains the second medicated layer component of gestation or estrogen antagonist and the medical grade silicone different with the active medicine in first medicated layer, wherein in described active medicine, by 100 weight portion active medicines, antiestrogen is the 40-70 weight portion, onapristone is the 30-60 weight portion, and the silicone or the high molecular polymer of active medicine and medical grade are pressed 1-70: the mixed of 99-30;
2. on second medicated layer, coat silicone rubber or medical macromolecular materials, obtain the controlled release layer that thickness is the 0.01-0.5 millimeter.Perhaps, the in utero medicament release device for preparing third aspect present invention through the following steps:
1. preparation drug layer valva:
The silicone or the high molecular polymer of active medicine and medical grade are pressed 1-70: the mixed of 99-30, wherein in described active medicine, by 100 weight portion active medicines, antiestrogen is the 40-70 weight portion, onapristone is the 30-60 weight portion; Mixture is put into mould carry out hot pressing, sulfuration forms drug layer valva;
2. the shoe of drug layer valva is attached
On the trailing arm of the internal layer of drug layer valva or support, be coated with one deck viscous liquid or friction produces static, drug layer valva is adhered on the support, form seamless cylindric;
3. the coating of release-controlled film
Be inserted in above-mentioned drug layer valva skin after the cylindrical tube swelling that silicone or high molecular polymer are made, or silicone or high molecular polymer be dissolved in the volatile liquid, adopt continuous ace, volatilization, repeatedly film forming mode forms controlled release layer, or adopts the combination of above-mentioned two kinds of methods.
Arrive shown in Fig. 3-3 as Fig. 3-1, employed mold shape is semicircle or fan-shaped in the preparation of described drug layer valva, but must assurance finally can be merged into complete cylinder type, preferred drug layer valva number is the 2-4 lobe, also can be pressed into cylindric or be extruded into cylindric by extruder by mould, as shown in Figure 4, then cylinder is withdrawed from from mould, be inserted in support; Or adopt cutter that cylindric medicated layer is opened from perpendicular end-grain cutting, and be some vertical semicircle lobes or small semicircle lobe, strip down from mould, cover again again to invest and be combined into the cylindrical tube shape medicated layer on the support.
Described controlled release layer preferably can form like this:
With silicone or medical high polymer polymer by extrude or mould pressing process make wall thickness evenly, size as one, even, the satisfactory cylindrical tube of weight.Then, with pipe be positioned over medical grade nonpolar, volatile, do not influence in the liquid of product quality performance, treat that its 2-4 that is swelled into original volume doubly after, be inserted in the skin that contains the cylindrical tube shape drug layer valva.Treat to form after liquid volatilizees naturally the dual controlled release medicine system of depot and speed controlled release.And, make to contain the lobe layer and do not come off and disperse simultaneously by means of the inside tightening force of outer release-controlled film.
2. a certain amount of silicone or medical high polymer polymer are fused and in volatile, as not influence drug quality technology, performance liquid, be made into dipping controlled release coating materials, to cover then with the support continuous impregnating that contains the lobe layer, volatilization, film forming 2-10 is all over (according to what of default release amount of medicine, determine the dipping pass, to form the outer release-controlled film of required thickness), finally be combined into the dual controlled release medicine system of compound depot speed release-controlled film.
3. first kind of release-controlled film method and second kind of release-controlled film method are met the multiple controlled release drug system of depot and speed release-controlled film in conjunction with formation, to reach different drug releases, the designing requirement of different meterings.
Described liquid volatile, that do not influence drug quality technology, performance is meant chloroform, ethers or hydro carbons etc.
Described silicone comprises HTV (high temperature vulcanized or heat cure, molecular weight 30-100 ten thousand), RTV-2 is (two-component room-temperature-vulcanized, molecular weight 0.74-11 ten thousand) or LTV (baking, molecular weight 400-20000), Dow corning SiLastic-382 medical grade silicone rubber, a Q7 medical grade silicone rubber series and an implantation level MDX series, or the medical grade silicon rubber of other respective series.
Described high molecular polymer comprises polyvinyl acetate (PVA), ethylene-acetate ethylene copolymer (EVAC), poly-acetic acid acetyl phthalic acid ester, methylcellulose, ethyl cellulose, polyvinyl acetate (PVA), polyacrylic resin class etc.
The specific embodiment
Take by weighing 300 milligrams of mifepristones, 200 milligrams of letrozoles, 0.1 gram sodium lauryl sulphate, 0.1 gram Arlacel-20 and 0.7 gram beta-schardinger dextrin-(molecular weight 1134, Shanghai reagent company produces), be packed into pipe thickness behind the mix homogeneously and be in 1 millimeter the medical grade silicon rubber pipe of silastic-382, put into mould, hot-forming.
Take by weighing certain amount of H TV medical grade rubber (molecular weight 30-100 ten thousand, Shanghai Rubber Products Insitute produces) and extrude the medical grade rubber ring that sulfidization molding is 5 centimetres of diameters.Take by weighing 300 milligrams of mifepristones, 200 milligrams of letrozoles, 0.015 gram Brij52 and 1.2 gram HTV medical grade rubber (molecular weight 30-100 ten thousand, Shanghai Rubber Products Insitute produces), be pressed into first thin skin of 1.2 millimeters thick after mixing, this first thin skin is coated on the above-mentioned medical grade rubber ring that makes; Take by weighing 200 milligrams of letrozoles, 0.01 gram Brij52 and 1 gram HTV medical grade rubber (molecular weight 30-100 ten thousand again, Shanghai Rubber Products Insitute produces), be pressed into second thin skin of 1.2 millimeters thick after mixing, this second thin skin is coated on first thin skin, coat the HTV medical grade silicon rubber thin skin of 0.02 millimeter of one deck on the article of gained again, compression molding.
Obtain managing the medical grade silicon rubber internal lining pipe that diameter is 4 millimeters RTV-1 (molecular weight 0.74-11 ten thousand, Shanghai Rubber Products Insitute) by extruding sulfidization molding, it is 5 centimetres open circles that crooked described internal lining pipe surrounds diameter.
Take by weighing 300 milligrams of HTV medical grade rubber (molecular weight 30-100 ten thousand, Shanghai Rubber Products Insitute produces), 400 milligrams of mifepristones, 0.3 gram sodium lauryl sulphate, 0.1 gram Arlacel-80 and 0.8 gram PEG 1200, take by weighing 200 milligrams of HTV medical grade rubber (molecular weight 30-100 ten thousand again, Shanghai Rubber Products Insitute produces), 250 milligrams of letrozoles, 0.1 gram sodium lauryl sulphate, 0.05 gram Arlacel-80 and 0.3 gram PEG1200, after mixing respectively, they are pressed into first thin skin and second thin skin separately, be coated on the internal lining pipe successively, again the RTV-1 medical grade silicon rubber is pressed into the thin skin of 0.02 millimeter thickness, be coated on the medicine thin skin, the hot-press vulcanization molding obtains required product.
Take by weighing 1 gram LTV (Shanghai Rubber Products Insitute), it is added in 20 milliliters of petroleum ether, mixing, it is standby to obtain impregnation liquid.
Take by weighing certain amount of H TV medical grade rubber (molecular weight 30-100 ten thousand, Shanghai Rubber Products Insitute produces) and extrude the medical grade rubber ring that sulfidization molding is 5 centimetres of diameters.Take by weighing 800 milligrams of HTV medical grade rubber (molecular weight 30-100 ten thousand, Shanghai Rubber Products Insitute's product), 400 milligrams of mifepristones, take by weighing 250 milligrams of letrozoles, 0.15 gram dodecyl sodium sulfate and 0.8 gram PEG 20000 again, be pressed into thin skin after the mixing and be coated on the medical grade rubber ring of gained, the ring of gained is immersed in the above-mentioned impregnation liquid that obtains, takes out after 5 seconds and dry.
(1) take by weighing medical grade LS-4100 addition-type silicon rubber 20 grams, mifepristone 12 grams, letrozole 8 grams are put into 1/3 semicircle mould behind uniform mixing on the rubber mixing machine, and press cure becomes drug layer valva, and deburring intercepts long 1.9cm, the every lobe of heavy 45-47mg/.
(2) get polyethylene IUD plasticity support and put into dehydrated alcohol immersion two hours, drain, standby.
(3) satisfactory drug layer valva and IUD support are slightly rubbed back adheres to, outer field silicone controlled release pipe is put into a glass drying oven, be swelled into more than a times of original volume with chloroform, be inserted in the skin that contains cylindric drug layer valva again, after treating that it volatilizees naturally, form skin and return rubber controlled release pipe, its inwardly tightens up earlier and is coated on the release layer of being made up of the polylith drug layer valva, not make it come off, disperse, form the dual controlled release system of compound depot and speed release-controlled film.
Embodiment 6
(1) with mifepristone 3 gram, Reynolds former times phenol 7 grams and medical grade LS-4100 addition-type silicon rubber behind uniform mixing on the rubber mixing machine, be pressed into cylindric by mould, press cure becomes medicated layer, pastille bed thickness 0.75mm, internal diameter are that 1.5mm, external diameter are 3mm, deburring then intercepts the cylindric medicated layer of long 1.9cm, heavy 92mg.
(2) cylindric medicated layer is placed on the trailing arm of IUD support, is immersed in then and contains 10% EVAC: flood volatilization, film forming 2 times in the chloroform controlled release impregnated membranes solution.After treating that its solvent volatilizees fully naturally, be combined into the dual control medicine-releasing system of compound depot and speed release-controlled film.
Clinical trial example 1
43 years old nearly amounts in the period, 2 of woman are big, time in menstrual period is long, and has an intense pain with lacerated, and clinical examination and ultrasound diagnosis show uterus size 93 * 95 * 96, volume increases, form is full, sees the slightly strong echo light of similar round group in the rear wall flesh layer of uterus, the most about 71 * 66 * 59mm, it is clear that border echo is owed, internal echo is owed evenly, the colored multispectral demonstration of reining in, and blood flow signal is abundant.The endometrium thick 6.9mm that moves forward, no three-way.
Ultrasonic prompting: uterine volume increases (adenomyosis and adenomyoma acoustic image)
Case shows: this patient once took mifepristone 25mg according to doctor's advice, once a day, took continuously two months, found that the hepatic region does not relax, and lacked appetite expression weakness, this medicine of promptly stopping using.After ultrasound diagnosis shows that the big small size in uterus, muscular tumor are not seen and dwindles.
Change estrogen antagonist and the compound pessary of gestation of embodiment 1 to patient.After 3 months, ultrasound diagnosis shows that this big small size in patient uterus, muscular tumor have obviously and dwindles, uterus size volume-diminished 27%, muscular tumor size volume-diminished 22.6%,: amenorrhea three months (pharmacological), pain perception complete obiteration, endometrium do not have the phenomenon of thickening (6.1mm), do not have not Shu Fanying of any whole body or part.Continue to use this estrogen antagonist and the compound pessary of gestation after 3 months, ultrasound diagnosis shows that this big small size in patient uterus, muscular tumor have more obviously and dwindles, uterus size volume-diminished 30%, muscular tumor size volume-diminished 27.1%,: amenorrhea three months (pharmacological), pain perception complete obiteration, endometrium do not have the phenomenon of thickening (6.5mm), do not have not Shu Fanying of any whole body or part.
Clinical trial example 2
Use the mifepristone pessaries for 6 examples and hysteromyoma does not have estrogen antagonist and the compound pessary of gestation that the patient who obviously dwindles changes embodiment 2, behind 3 first quarter moons, show that through ultrasound diagnosis every patient's hysteromyoma all has dwindle (10-30%) in various degree.
Clinical trial example 3
Give the single mifepristone pessary of former use and hysteromyoma does not have the in utero medicament release device that 3 patients that obviously dwindle use embodiment 5 or 6 preparations, behind 3 first quarter moons, show that through ultrasound diagnosis every patient's hysteromyoma also all has dwindle (18-25%) in various degree.
Therefore, pessary of the present invention or in utero medicament release device have following characteristics: release is slow, constant, lasting, long-term, discharge medicine in the uterine cavity circulation target organ and reach therapeutic purposes, thereby make active stronger hormone can avoid explosion impact and the surplus post dose defect of insufficient that begins to measure, and the side effect that systemic administration brought.
Claims (20)
1. pessary, it comprises the pastille part and is coated on silastic-layer on the pastille part; Described pastille partly comprises, by pastille part gross weight, and 5-70 weight active medicine, the physiology of acceptable surfactant and surplus goes up acceptable dispersant on the 0.5-20 weight % physiology.The described thickness that is coated on the silastic-layer on the pastille part is the 0.01-0.5 millimeter; It is characterized in that in described active medicine, by 100 weight portion active medicines, antiestrogen is the 40-70 weight portion, onapristone is the 30-60 weight portion.
2. pessary according to claim 1, wherein said antiestrogen are selected from Reynolds former times phenol, tamoxifen, NSC-70735 or aromatase inhibitor; Described onapristone is selected from mifepristone or gestrinone.
3. pessary according to claim 1, wherein said aromatase inhibitor is selected from Anna's Si azoles, Ai Simeitan and letrozole.
4. pessary according to claim 3, wherein said active medicine is made up of the mifepristone of 60% weight and the letrozole of 40% weight.
5. pessary according to claim 1, wherein said pastille part is by first medicated layer part that contains estrogen antagonist or gestation and contain gestation or antiestrogenic second medicated layer is formed, condition is, if first medicated layer contains gestation, then second medicated layer contains estrogen antagonist; If first medicated layer contains estrogen antagonist, then second medicated layer contains gestation.
6. pessary according to claim 5, wherein said first pastille partly is positioned at the center of pessary, and second pastille partly is coated on first pastille part at center.
7. pessary according to claim 1, wherein the center of pessary comprises the hollow parts that is surrounded by internal lining pipe, the pastille part is between internal lining pipe and silicone rubber coating.Described internal lining pipe can be made of above-mentioned medical grade silicon rubber and other medical high polymer polymer.
8. pessary according to claim 5, the center of wherein said pessary comprises the medical grade silicon rubber post, described first medicated layer partly is coated on the medical grade rubber post, coating on second medicated layer on first medicated layer, coats silastic-layer again on second medicated layer.
9. pessary according to claim 1, the wherein said silastic-layer thickness that is coated on the pastille part is the 0.02-1 millimeter.
10. intrauterine medicament release device, comprise medicine-feeder support in utero, be coated on the support first medicated layer and in second medicated layer on first medicated layer and be coated on controlled release layer on second medicated layer, described first medicated layer and second medicated layer are formed by the silicone of active medicine that is independently selected from antiestrogen and onapristone and medical grade or the high molecular polymer mixed by 1-70: 99-30, condition is when first medicated layer contains estrogen antagonist, and second medicated layer then contains gestation; Perhaps when first medicated layer contained gestation, second medicated layer then contained estrogen antagonist, it is characterized in that, in described active medicine, by 100 weight portion active medicines, antiestrogen is the 40-70 weight portion, and onapristone is the 30-60 weight portion.
11. medicament release device in utero, comprise in utero the medicine-feeder support, be coated on and contain the lobe layer on the support and be coated on the controlled release layer that contains on the lobe layer, the described lobe layer that contains is formed by the silicone of active medicine and medical grade or the high molecular polymer mixed by 1-70: 99-30, it is characterized in that, in described active medicine, by 100 weight portion active medicines, antiestrogen is the 40-70 weight portion, and onapristone is the 30-60 weight portion.
12. according to claim 10 or 11 described in utero medicament release device, wherein said antiestrogen is selected from Reynolds former times phenol, tamoxifen, NSC-70735 or aromatase inhibitor; Described onapristone is selected from mifepristone or gestrinone, and described aromatase preferably is selected from Anna's Si azoles, Ai Simeitan and letrozole.
13. according to claim 10 or 11 described in utero medicament release device, wherein said active medicine is made up of the mifepristone of 60% weight and the letrozole of 40% weight.
14. according to claim 10 or 11 described in utero medicament release device, wherein in utero the medicine-feeder support is the liner non-toxic polyvinyl chloride support or the silicone rubber support of T type, Y type, umbellate form.
15. according to claim 10 or 11 described in utero medicament release device, wherein each in utero the active medicine content in the medicament release device be 30mg-200mg.
16. in utero medicament release device according to claim 15, wherein each in utero the active medicine content in the medicament release device be 10-50mg.
17. according to claim 10 or 11 described in utero medicament release device, wherein said release-controlled film is made up of silicone or medical high polymer polymer, its thickness is 0.01-0.5mm.
18. in utero medicament release device according to claim 17, the thickness of wherein said release-controlled film are 0.05-0.5mm.
19. as the application of the arbitrary described pessary of claim 1-9 in preparation treatment hysteromyoma medicine or endometriosis medicine.
20. as the application of the arbitrary described in utero medicament release device of claim 10-18 in preparation treatment hysteromyoma medicine or endometriosis medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510027902 CN1899643B (en) | 2005-07-20 | 2005-07-20 | Pessary or intrauterine medicine release device containing antiestrogenic and anti-pregnant hormone composite preparation and its use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510027902 CN1899643B (en) | 2005-07-20 | 2005-07-20 | Pessary or intrauterine medicine release device containing antiestrogenic and anti-pregnant hormone composite preparation and its use |
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| Publication Number | Publication Date |
|---|---|
| CN1899643A true CN1899643A (en) | 2007-01-24 |
| CN1899643B CN1899643B (en) | 2010-12-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 200510027902 Active CN1899643B (en) | 2005-07-20 | 2005-07-20 | Pessary or intrauterine medicine release device containing antiestrogenic and anti-pregnant hormone composite preparation and its use |
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| Country | Link |
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| CN (1) | CN1899643B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102497855A (en) * | 2009-07-21 | 2012-06-13 | 人口委员会股份有限公司 | Multi-layered gradient vaginal ring |
| CN102861374A (en) * | 2011-07-08 | 2013-01-09 | 上海市计划生育科学研究所 | Pessulum capable of steadily releasing medicine |
| CN109925538A (en) * | 2018-04-19 | 2019-06-25 | 易浦润（上海）生物技术有限公司 | A kind of elastic membrane, preparation method and application |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103007427B (en) * | 2011-09-21 | 2016-01-20 | 上海市计划生育科学研究所 | Slow controlled release in utero medicine-feeder and preparation method thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4180064A (en) * | 1972-12-27 | 1979-12-25 | Alza Corporation | System for delivering agent to environment of use over prolonged time |
| DE3040978A1 (en) * | 1980-10-28 | 1982-05-27 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | VAGINAL RING |
| TW358031B (en) * | 1997-04-11 | 1999-05-11 | Akze Nobel N V | Drug delivery system for 2 or more active substances |
| CN1210079C (en) * | 2001-04-25 | 2005-07-13 | 上海市计划生育科学研究所 | Medicine for vaginal ring and its application |
| CN2525971Y (en) * | 2001-11-13 | 2002-12-18 | 程定超 | Pessary of slow-released mifepristone |
| CN1242819C (en) * | 2002-06-07 | 2006-02-22 | 上海市计划生育科学研究所 | Novel pessary and method for preparing same |
-
2005
- 2005-07-20 CN CN 200510027902 patent/CN1899643B/en active Active
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102497855A (en) * | 2009-07-21 | 2012-06-13 | 人口委员会股份有限公司 | Multi-layered gradient vaginal ring |
| CN102497855B (en) * | 2009-07-21 | 2013-12-25 | 人口委员会股份有限公司 | Multi-layered gradient vaginal ring |
| US8753667B2 (en) | 2009-07-21 | 2014-06-17 | The Population Council, Inc. | Multi-layered gradient vaginal ring |
| CN102861374A (en) * | 2011-07-08 | 2013-01-09 | 上海市计划生育科学研究所 | Pessulum capable of steadily releasing medicine |
| CN102861374B (en) * | 2011-07-08 | 2014-06-25 | 上海市计划生育科学研究所 | Pessulum capable of steadily releasing medicine |
| CN109925538A (en) * | 2018-04-19 | 2019-06-25 | 易浦润（上海）生物技术有限公司 | A kind of elastic membrane, preparation method and application |
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| Publication number | Publication date |
|---|---|
| CN1899643B (en) | 2010-12-29 |
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