WO2010043950A2 - Propafenone extended release composition - Google Patents
Propafenone extended release composition Download PDFInfo
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- WO2010043950A2 WO2010043950A2 PCT/IB2009/007126 IB2009007126W WO2010043950A2 WO 2010043950 A2 WO2010043950 A2 WO 2010043950A2 IB 2009007126 W IB2009007126 W IB 2009007126W WO 2010043950 A2 WO2010043950 A2 WO 2010043950A2
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- propafenone
- diluent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
Definitions
- the technical field of the present invention relates to extended release compositions of antiarrythmic drug. More particularly, the present invention relates to extended release compositions of propafenone hydrochloride.
- Propafenone hydrochloride belongs to the class of ⁇ - phenylpropiophenone derivatives. It is an antiarrhythmic drug used to prolong the time to recurrence of symptomatic atrial fibrillation in patients without structural heart disease, paroxysmal atrial fibrillation/flutter (PAF) and paroxysmal supraventricular tachycardia (PSVT).
- PAF paroxysmal atrial fibrillation/flutter
- PSVT paroxysmal supraventricular tachycardia
- Propafenone hydrochloride is commercially available as immediate release tablets and extended release capsules under the trade name Rythmol ® and Rythmol SR ® in the United States.
- Rythmol SR ® capsules are filled with cylindrical shaped 2 x 2 mm micro tablets containing 225, 325 and 425 mg of propafenone and excipients include antifoam, gelatin, hypromellose, red iron oxide, magnesium stearate, shellac, sodium lauryl sulfate, sodium dodecyl sulfate, soy lecithin and titanium dioxide.
- US 5,681,588 disploses . that in the prior art the release of active ingredient from tablets is delayed either by a release-delaying matrix in which the active ingredient is embedded, or by a release-delaying coating through which the digestive fluid diffuses in and the active ingredient diffuses out, which is disadvantageous as matrix tablets contain relatively large amounts of ancillary substances so that the volume of the tablet for a given dose of active ingredient is relatively large, which jis unpleasant for the patient and on the. other hand, film-coated tablets are elaborate to produce.
- Example 5 of US 4,797,287 discloses that 1 ,600 g of propafenone was i . mixed with 250 g of microcrystalline cellulose, lOOg of lactose, 4Og of talc and
- US 2005/0271718 discloses that the microtablets actually contained in Rythmol SR ® capsules have a diameter of 2 mm with propafenone hydrochloride content of 6.25 mg, and a total weight of 6.5 mg per microtablet. Because the propafenone hydrochloride content is 6.25 mg per microtablet, it follows that the number of microtablets required per capsule is 36 for 225 mg capsules, 52 for 325 mg capsules, and 68 for 425 mg capsules. It is relatively expensive to produce large quantities of microtablets on conventional rotary tablet presses and the tooling needed to produce microtablets of 2 mm diameter is relatively fragile and easily broke. To overcome this US '718 discloses sustained release capsule comprising 25 mg propafenone hydrochloride tablets so that the capsules of strength 225 mg, 325 mg and 425 mg will contain 9, 13 and 17 tablets respectively. ;
- US 2008/0014257 discloses capsule comprising non-uniform pellets, having a non-uniform shape and/or size of propafenone prepared by compressing a powder comprising propafenone into slugs and breaking the slugs into nonuniform pellets and further discloses that the dosage form comprise 78.5 to about 79.5% by weight of propafenone.
- WO 2005/120481 discloses a capsule containing microtablets of propafenone with less than 0.1% of lubricant prepared by compacting propafenone and then milling into small granules followed by compressing into micro tablets of 12.5 mg weight.
- WO 2009/042778 discloses sustained release composition in pellet form comprising propafenone, water-soluble polymer, water-insoluble polymer prepared by extrusion-spheronisation and further discloses the amount of propafenone present in composition is more than 80%.
- the rriain objective of the present invention is to provide extended release dosage form of propafenone hydrochloride.
- Yet another objective of the present invention is to provide extended release dosage form of propafenone hydrochloride in such a way that it will comply with the reference product in terms of in vivo parameters like C max , t max , AUC and in vitro parameters like dissolution etc.
- Yet another objective of the present invention is to provide process for the preparation of extended release dosage form of propafenone hydrochloride.
- the main embodiment of the present invention is to provide an extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride and one or more pharmaceutically acceptable excipients, wherein said dosage form is essentially free of release retarding excipients.
- Fig.l illustrates the comparative dissolution profile of Rythmol SR capsules and Example 1.
- Fig.2 illustrates the comparative dissolution profile of Rythmol SR capsules and Example 2.
- Fig.3 illustrates the comparative dissolution profile of Rythmol SR capsules and Example 3.
- Fig.4 illustrates the comparative dissolution profile of Rythmol SR capsules and Example 4. .
- the pharmaceutically acceptable excipient includes diluent, binder and lubricant.
- the extended release dosage form containing low concentration of propafenone that has release profile similar to that of Rythmol SR capsules can be achieved by careful selection of excipients, depending on its solubility and swelling nature in water.
- Suitable diluents used according to the present invention are selected from water soluble or water insoluble diluents or combination thereof.
- Suitable water soluble diluents include lactose, sucrose, mannitol, sorbitol, modified starches, citric acid, furmaric acid, tartaric acid, sodium chloride, glycine, low viscosity cellulose ethers and the like; and water insoluble diluents include calcium phosphates, alkali or alkaline earth metal carbonates, alkali or alkaline earth metal oxides, insoluble resins and the like or combination there of.
- the amount of diluent may range from about 10% to 40% by weight.
- the in vitro release of the active ingredient can be modulated based on the erosion pattern of mini tablets.
- lactose monohydrate and dibasic i calcium phosphate when used as a diluent in the formulation shows a release profile similar to that of Rythmol SR capsules.
- the similar release profile might be due to soluble and non swellable property of lactose monohydrate and insoluble property of dibasic calcium phosphate when exposed to water. This leads to a slower erosion of the mini tablets there by extending the release of propafenone. .
- excipient is water swellable, the in vitro release of the active ingredient is found to increase due to faster disintegration of the mini tablets.
- excipients like starch, microcrystalline cellulose which has swelling tendency in presence of * water shows a faster release profile compared to Rythmol SR capsules.
- Suitable binders used according to the present invention are selected from the group comprising of hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, pregelatinized starch and the like.
- the amount of binder may range from about 0.5% to 2% by weight.
- Suitable lubricants iused according to the present invention are selected from magnesium stearate, calcium stearate, sodium stearyl fumarate, talc, vegetable oils, stearic acid, fumaric acid, glyceryl behenate and the like.
- the mini tablets of the present invention are prepared either by dry granulation or wet granulation.
- a process for the preparation of extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride and one or more pharmaceutically acceptable excipients, wherein said dosage form is essentially free of release retarding excipients comprising the steps of: (i) granulating propafenone hydrochloride and diluent using binder solution, (ii) drying the granules of step (i), (iii) lubricating the dried granules of step (ii),
- step (iv) compressing the lubripated granules of step (iii) using 2.5mm punches into minitablets.
- extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride, about 10% ; to 40% by weight of diluent, about 0.5% to 2% by weight of binder and about 0.5% to 2% by weight of lubricant, wherein said dosage form is essentially free of release retarding excipients.
- extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride, about 10% to 40% by weight of diluent selected from lactose or dibasic calcium phosphate or combination thereof; about 0.5% to
- binder selected from hydroxypropylmethyl cellulose or povidone and about 0.5% tjo 2% by weight of lubricant selected from magnesium stearate or sodium stearyl fumarate, wherein said dosage form is essentially free of release retarding excipients.
- the mini tablets may be uncoated or optionally coated.
- the solid dosage form is a capsule comprising the mini tablets encapsulated ih a shell.
- step (ii) granulated the blended material of step (i) with solution of hydroxypropylmethylcellulose in water
- step (iii) the granules of step (ii) were dried and sized through 40 mesh
- step (iv) the granules of step (iii) were lubricated with magnesium stearate, (v) the lubricated granules of step (iv) was compressed using 2.5mm punches into minitablets and
- compositions described in example 2-4 were prepared using the procedure similar to the one described in example 1.
- the dissolution profile of the extended release capsules of propafenone prepared according to the present invention was carried out in 900 ml of 0.08N hydrochloric acid for 2 hours, followed by 900 ml of pH 6.8 phosphate buffer as medium according to the procedure described in the USP, Apparatus USP II, Paddle, @ 50 rpm speed.
- the release profile (% of drug released in hours) is depicted in figures.
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Abstract
An extended release propafenone mini tablets composition with in vitro release profile similar to that of Rythmol SR capsules without using any release retarding excipient wherein thee concentration of propafenone is less than or equal to 80%w/w.
Description
PROPAFENONE EXTENDED RELEASE COMPOSITION
Field of the invention
The technical field of the present invention relates to extended release compositions of antiarrythmic drug. More particularly, the present invention relates to extended release compositions of propafenone hydrochloride.
Background of the invention
Propafenone hydrochloride belongs to the class of β- phenylpropiophenone derivatives. It is an antiarrhythmic drug used to prolong the time to recurrence of symptomatic atrial fibrillation in patients without structural heart disease, paroxysmal atrial fibrillation/flutter (PAF) and paroxysmal supraventricular tachycardia (PSVT).
Propafenone hydrochloride is commercially available as immediate release tablets and extended release capsules under the trade name Rythmol® and Rythmol SR® in the United States. Rythmol SR® capsules are filled with cylindrical shaped 2 x 2 mm micro tablets containing 225, 325 and 425 mg of propafenone and excipients include antifoam, gelatin, hypromellose, red iron oxide, magnesium stearate, shellac, sodium lauryl sulfate, sodium dodecyl sulfate, soy lecithin and titanium dioxide.
US 5,681,588 disploses . that in the prior art the release of active ingredient from tablets is delayed either by a release-delaying matrix in which the active ingredient is embedded, or by a release-delaying coating through which the digestive fluid diffuses in and the active ingredient diffuses out, which is disadvantageous as matrix tablets contain relatively large amounts of ancillary substances so that the volume of the tablet for a given dose of active ingredient is relatively large, which jis unpleasant for the patient and on the. other hand, film-coated tablets are elaborate to produce. To overcome these disadvantages of prior art, the inventors of US '588 have surprisingly found that by preparing a micro tablet with specific size and shape' i.e.: cylindrical shaped with a convex or flat upper side and lower side with the height and diameter 1-3 mm, and with the active ingredient content 8;1 to 99.9% by weight of microtablet, it is possible to
produce a delayed release tablet having improved release characteristics without using any release delaying ancillary substances.
'I
The following patents/patent publications further disclose different ways to obtain extended release compositions of propafenone: Example 5 of US 4,797,287 discloses that 1 ,600 g of propafenone was i . mixed with 250 g of microcrystalline cellulose, lOOg of lactose, 4Og of talc and
1Og of magnesium stearate and then compressed in to mini tablets having a diameter of 2.1 mm and a height of 2.0 mm. The Propafenone mini tablets were then coated, in a fluidized-bed spray granulator with a 20% w/w aqueous solution of hydroxypropylmethylcellulose, wherein the total amount of the coating polymer was 5% based on the coated propafenone mini tablets.
US 2005/0271718 discloses that the microtablets actually contained in Rythmol SR® capsules have a diameter of 2 mm with propafenone hydrochloride content of 6.25 mg, and a total weight of 6.5 mg per microtablet. Because the propafenone hydrochloride content is 6.25 mg per microtablet, it follows that the number of microtablets required per capsule is 36 for 225 mg capsules, 52 for 325 mg capsules, and 68 for 425 mg capsules. It is relatively expensive to produce large quantities of microtablets on conventional rotary tablet presses and the tooling needed to produce microtablets of 2 mm diameter is relatively fragile and easily broke. To overcome this US '718 discloses sustained release capsule comprising 25 mg propafenone hydrochloride tablets so that the capsules of strength 225 mg, 325 mg and 425 mg will contain 9, 13 and 17 tablets respectively. ;
US 2008/0014257 discloses capsule comprising non-uniform pellets, having a non-uniform shape and/or size of propafenone prepared by compressing a powder comprising propafenone into slugs and breaking the slugs into nonuniform pellets and further discloses that the dosage form comprise 78.5 to about 79.5% by weight of propafenone.
WO 2005/120481 discloses a capsule containing microtablets of propafenone with less than 0.1% of lubricant prepared by compacting
propafenone and then milling into small granules followed by compressing into micro tablets of 12.5 mg weight.
WO 2009/042778 discloses sustained release composition in pellet form comprising propafenone, water-soluble polymer, water-insoluble polymer prepared by extrusion-spheronisation and further discloses the amount of propafenone present in composition is more than 80%.
The above prior art references discloses different ways of attaining the sustained release formulations of propafenone. An extended release formulation with very high concentration of active ingredient needs a very well defined particle size specification of the active ingredient as well as highly controlled process parameters for manufacturing like granulation, sizing of the dried granules, lubrication of the final blend and compression. Since the solubility of propafenone is more than lmg /ml across the pH range of 1 to 6.8, it is a challenge to make a formulation containing propafenone less than or equal to 80 % by weight without using any release retarding excipient. As the concentration of the active ingredient reduces, there is a possibility of increase in dissolution.
Hence, there exists a need to make a robust mini tablet formulation which is easy to manufacture and has the release profile similar to that of the marketed product
Rythmol SR capsules without using release retarding excipients. Objective of the invention
Accordingly, the rriain objective of the present invention is to provide extended release dosage form of propafenone hydrochloride.
Yet another objective of the present invention is to provide extended release dosage form of propafenone hydrochloride in such a way that it will comply with the reference product in terms of in vivo parameters like Cmax, tmax, AUC and in vitro parameters like dissolution etc.
Yet another objective of the present invention is to provide process for the preparation of extended release dosage form of propafenone hydrochloride.
Summary of the invention
Accordingly, the main embodiment of the present invention is to provide an extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride and one or more pharmaceutically acceptable excipients, wherein said dosage form is essentially free of release retarding excipients.
Brief description of the Drawings
Fig.l illustrates the comparative dissolution profile of Rythmol SR capsules and Example 1. Fig.2 illustrates the comparative dissolution profile of Rythmol SR capsules and Example 2.
Fig.3 illustrates the comparative dissolution profile of Rythmol SR capsules and Example 3.
Fig.4 illustrates the comparative dissolution profile of Rythmol SR capsules and Example 4. .
Detailed description of the invention
In another embodiment, the pharmaceutically acceptable excipient includes diluent, binder and lubricant.
The extended release dosage form containing low concentration of propafenone that has release profile similar to that of Rythmol SR capsules can be achieved by careful selection of excipients, depending on its solubility and swelling nature in water. -
Suitable diluents used according to the present invention are selected from water soluble or water insoluble diluents or combination thereof. Suitable water soluble diluents include lactose, sucrose, mannitol, sorbitol, modified starches, citric acid, furmaric acid, tartaric acid, sodium chloride, glycine, low viscosity cellulose ethers and the like; and water insoluble diluents include calcium phosphates, alkali or alkaline earth metal carbonates, alkali or alkaline earth metal oxides, insoluble resins and the like or combination there of. The amount of diluent may range from about 10% to 40% by weight.
If the excipient is water soluble or insoluble and non swellable in water, the in vitro release of the active ingredient can be modulated based on the erosion pattern of mini tablets. For example lactose monohydrate and dibasic i calcium phosphate, when used as a diluent in the formulation shows a release profile similar to that of Rythmol SR capsules. The similar release profile might be due to soluble and non swellable property of lactose monohydrate and insoluble property of dibasic calcium phosphate when exposed to water. This leads to a slower erosion of the mini tablets there by extending the release of propafenone. . And if the excipient is water swellable, the in vitro release of the active ingredient is found to increase due to faster disintegration of the mini tablets. For example excipients like starch, microcrystalline cellulose which has swelling tendency in presence of * water shows a faster release profile compared to Rythmol SR capsules. Suitable binders used according to the present invention are selected from the group comprising of hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, pregelatinized starch and the like. The amount of binder may range from about 0.5% to 2% by weight.
Suitable lubricants iused according to the present invention are selected from magnesium stearate, calcium stearate, sodium stearyl fumarate, talc, vegetable oils, stearic acid, fumaric acid, glyceryl behenate and the like.
In another embodiment, the mini tablets of the present invention are prepared either by dry granulation or wet granulation.
In another embodiment, there is provided a process for the preparation of extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride and one or more pharmaceutically acceptable excipients, wherein said dosage form is essentially free of release retarding excipients comprising the steps of: (i) granulating propafenone hydrochloride and diluent using binder solution, (ii) drying the granules of step (i),
(iii) lubricating the dried granules of step (ii),
(iv) compressing the lubripated granules of step (iii) using 2.5mm punches into minitablets. i
In a preferred embodiment, extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride, about 10%; to 40% by weight of diluent, about 0.5% to 2% by weight of binder and about 0.5% to 2% by weight of lubricant, wherein said dosage form is essentially free of release retarding excipients.
In another preferred embodiment, extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride, about 10% to 40% by weight of diluent selected from lactose or dibasic calcium phosphate or combination thereof; about 0.5% to
2% by weight of binder selected from hydroxypropylmethyl cellulose or povidone and about 0.5% tjo 2% by weight of lubricant selected from magnesium stearate or sodium stearyl fumarate, wherein said dosage form is essentially free of release retarding excipients. .
In another embodiment, the mini tablets may be uncoated or optionally coated.
In another embodiment, the solid dosage form is a capsule comprising the mini tablets encapsulated ih a shell.
The following examples further exemplify the invention and are not intended to limit the scope of the invention'. It is obvious to those skilled in the art to find out the composition for other dosage forms and substitute the equivalent excipients as described in this specification or with the one known to the industry.
Example 1: Propafenone hydrochloride Extended Release capsules
The processing steps involved in manufacturing propafenone extended release capsules as given in example 1 are given below: (i) propafenone and dibasic calcium phosphate were sifted and blended,
(ii) granulated the blended material of step (i) with solution of hydroxypropylmethylcellulose in water,
(iii) the granules of step (ii) were dried and sized through 40 mesh,
(iv) the granules of step (iii) were lubricated with magnesium stearate, (v) the lubricated granules of step (iv) was compressed using 2.5mm punches into minitablets and
(vi) the minitablets were then filled in capsules.
I-
The compositions described in example 2-4 were prepared using the procedure similar to the one described in example 1.
Comparative study of Prbpafenone hydrochloride extended release capsules using microcrystalline cellulose as diluent
Example 2: Propafenone hydrochloride Extended Release capsules
Example 4: Propafenone hydrochloride Extended Release capsules
The dissolution profile of the extended release capsules of propafenone prepared according to the present invention was carried out in 900 ml of 0.08N hydrochloric acid for 2 hours, followed by 900 ml of pH 6.8 phosphate buffer as medium according to the procedure described in the USP, Apparatus USP II, Paddle, @ 50 rpm speed. The release profile (% of drug released in hours) is depicted in figures.
Claims
1. An extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride and one or more pharmaceutically acceptable excipients, wherein said dosage form is essentially free of release retarding excipients.
2. The dosage form of ! claim 1, wherein the pharmaceutically acceptable excipient includes diluent, binder and lubricant.
3. The dosage form of claim 2, wherein the diluent is selected from water soluble or water insoluble or combination thereof.
4. The dosage form of claim 3, wherein the water soluble diluent is selected from lactose, sucrose, maηnitol, sorbitol, modified starches, citric acid, furmaric acid, tartaric acid, sodium chloride, glycine or combination thereof.
5. The dosage form of claim 3, wherein the water insoluble diluent is selected from calcium phosphates, alkali or alkaline earth metal carbonates, alkali or alkaline earth metal oxides, insoluble resins or combination thereof.
6. The dosage form of claim 2, wherein the binder is selected from of hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, pregelatinized starch.
7. An extended release dosage form comprises mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride, about 10% to 40% by weight of diluent, about 0.5% to 2% by weight of binder and about 0.5% to 2% by weight of lubricant, wherein said dosage form is essentially free of release retarding excipients.
8. An extended release dosage form comprises mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride, about 10% to 40% by weight of diluent selected from lactose or dibasic calcium phosphate or combination thereof; about 0.5% to 2% by weight of binder selected from hydroxypropylmethylcellulose or povidone and about 0.5% to 2% by weight of lubricant selected from magnesium stearate or sodium stearyl fumarate, wherein i said dosage form is essentially free of release retarding excipients.
9. A process for the preparation of extended release dosage form comprising mini tablets comprising less than or equal to 80% by weight of propafenone hydrochloride and one or more pharmaceutically acceptable excipients, wherein said dosage form is essentially free of release retarding excipients comprising the steps of:
(i) granulating propafenone hydrochloride and diluent using binder solution, (ii) drying the granules of step (i), (iii) lubricating the dried granules of step (ii),
(iv) compressing the lubricated granules of step (iii) using 2.5mm punches into minitablets.
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WO2011154012A1 (en) * | 2010-06-10 | 2011-12-15 | Lifecycle Pharma A/S | Mini-tablets comprising porous adsorbent material |
CN103432094A (en) * | 2013-09-11 | 2013-12-11 | 中国药科大学 | Propafenone hydrochloride sustained-release preparation and preparation method thereof |
CN105213349A (en) * | 2015-10-10 | 2016-01-06 | 赛乐医药科技(上海)有限公司 | A kind of propafenone hydrochloride sustained-release micro-pill capsules agent and its preparation method and application |
CN105902984A (en) * | 2016-05-29 | 2016-08-31 | 山东仁和堂药业有限公司 | Propafenone hydrochloride tablets and preparation method thereof |
CN109394722A (en) * | 2018-12-26 | 2019-03-01 | 上海宣泰医药科技有限公司 | Propafenone microplate, multiple-unit formulation comprising the microplate and its preparation method and application |
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US11065138B2 (en) | 2016-05-13 | 2021-07-20 | Jenavalve Technology, Inc. | Heart valve prosthesis delivery system and method for delivery of heart valve prosthesis with introducer sheath and loading system |
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US11278398B2 (en) | 2003-12-23 | 2022-03-22 | Boston Scientific Scimed, Inc. | Methods and apparatus for endovascular heart valve replacement comprising tissue grasping elements |
US11337800B2 (en) | 2015-05-01 | 2022-05-24 | Jenavalve Technology, Inc. | Device and method with reduced pacemaker rate in heart valve replacement |
US11357624B2 (en) | 2007-04-13 | 2022-06-14 | Jenavalve Technology, Inc. | Medical device for treating a heart valve insufficiency |
US11517431B2 (en) | 2005-01-20 | 2022-12-06 | Jenavalve Technology, Inc. | Catheter system for implantation of prosthetic heart valves |
US11564794B2 (en) | 2008-02-26 | 2023-01-31 | Jenavalve Technology, Inc. | Stent for the positioning and anchoring of a valvular prosthesis in an implantation site in the heart of a patient |
US11589981B2 (en) | 2010-05-25 | 2023-02-28 | Jenavalve Technology, Inc. | Prosthetic heart valve and transcatheter delivered endoprosthesis comprising a prosthetic heart valve and a stent |
CN117462502A (en) * | 2023-10-26 | 2024-01-30 | 山东丰金生物医药有限公司 | Novel propafenone hydrochloride sustained-release composition and preparation method thereof |
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