WO2021196982A1 - 一种抗心律失常的药物组合物及制备方法 - Google Patents
一种抗心律失常的药物组合物及制备方法 Download PDFInfo
- Publication number
- WO2021196982A1 WO2021196982A1 PCT/CN2021/079508 CN2021079508W WO2021196982A1 WO 2021196982 A1 WO2021196982 A1 WO 2021196982A1 CN 2021079508 W CN2021079508 W CN 2021079508W WO 2021196982 A1 WO2021196982 A1 WO 2021196982A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutical composition
- lactose
- pregelatinized starch
- microcrystalline cellulose
- composition according
- Prior art date
Links
Images
Classifications
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- 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 invention belongs to the field of pharmaceutical preparations, and more specifically, relates to an anti-arrhythmic pharmaceutical composition and a preparation method.
- SCD Sudden cardiac death
- VT continuous ventricular tachycardia
- VF ventricular fibrillation
- Patent ZL200710181295.7 discloses 1-(3-methanesulfonamidobenzyl)-6-methoxy, 7-benzyloxy-1,2,3,4-tetrahydroisoquinoline (hereinafter referred to as compound A) Or its salt, which is known as a class III antiarrhythmic drug, has prolonged action potential duration, and is effective for ventricular tachycardia and ventricular fibrillation.
- the purpose of the present invention is to provide an antiarrhythmic pharmaceutical composition with good stability and rapid dissolution and a preparation method thereof.
- the pharmaceutical composition proposed by the present invention includes:
- Active ingredients including 1-(3-methanesulfonamidobenzyl)-6-methoxy, 7-benzyloxy-1,2,3,4-tetrahydroisoquinoline or a pharmaceutically acceptable salt thereof ;
- the auxiliary materials include 30%-80% lactose, microcrystalline cellulose and pregelatinized starch based on the total weight of the composition.
- lactose, microcrystalline cellulose and pregelatinized starch account for 40% to 60% of the total weight of the composition.
- the weight ratio of the lactose, microcrystalline cellulose and pregelatinized starch is 1:1.8-2.2:0.9-1.1. Preferably, it is 1:1.9 to 2.1: 0.9 to 1.1. More preferably, 1:2:1.
- the pharmaceutical composition further includes a disintegrant; wherein, the disintegrant is selected from sodium carboxymethyl starch, croscarmellose sodium, low-substituted hydroxypropyl cellulose and cross-linked polyvinyl cellulose At least one of ketones.
- the disintegrant is selected from sodium carboxymethyl starch, croscarmellose sodium, low-substituted hydroxypropyl cellulose and cross-linked polyvinyl cellulose At least one of ketones.
- the content of the disintegrant is selected from 1-30% based on the total weight of the composition, preferably 2-20% by weight, more preferably 2.5-4%.
- the pharmaceutical composition further includes a lubricant; wherein,
- the lubricant is selected from at least one of magnesium stearate, zinc stearate, glyceryl behenate, sodium lauryl sulfate, hydrogenated vegetable oil, micronized silica gel, talcum powder, and colloidal silicon dioxide, preferably stearin At least one of magnesium acid and colloidal silica.
- the lubricant content is selected from 0.5% to 5% based on the total weight of the composition, preferably 0.7%.
- the pharmaceutical composition may be granules, tablets or capsules obtained from the active ingredients and the adjuvants through processes including mixing, granulating and drying.
- the content of the active ingredient is 5% to 70%, preferably 10% to 50%, more preferably 20 to 45% based on the total weight of the composition; when the pharmaceutical composition is a tablet, the active ingredient per tablet
- the specific weight of the content is 0.1 to 1000 mg, preferably 10 to 500 mg, more preferably 50 to 300 mg, and more preferably 100 mg.
- the pharmaceutically acceptable salt may be hydrochloride or phosphate.
- composition further includes an adhesive, wherein:
- the binder is selected from at least one of hypromellose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, and methyl cellulose; the content of the binder is selected from a combination based on 0.5-10% of the total weight of the substance, preferably 0.9%.
- the prescription weight ratio of the pharmaceutical composition is as follows:
- compound B is the phosphate of compound A.
- the present invention also proposes the use of the pharmaceutical composition as described in any one of the foregoing in anti-arrhythmia.
- the present invention also provides a method for preparing the aforementioned pharmaceutical composition, the method comprising:
- static drying or fluidized drying is selected as the drying.
- the granulation method adopts a high-speed shear granulation method or a fluidized bed spray granulation method.
- the method includes:
- Adopt hot air circulation oven 50°C blast drying
- the present invention screens the types and dosage ratios of various excipients, and finally obtains a pharmaceutical composition with the characteristics of rapid dissolution and good stability. Under the condition of 0.01 mol/L hydrochloric acid solution medium, the dissolution rate (%) of the active ingredient in the pharmaceutical composition reaches 80% or higher within 30 minutes.
- the preparation process of the pharmaceutical composition is simple, and is more suitable for process-oriented mass production.
- Figure 1 is the dissolution profile of the pharmaceutical composition of the present invention using water as the dissolution medium.
- Figure 2 is the dissolution curve of the pharmaceutical composition of the present invention using 0.01 mol/L hydrochloric acid as the dissolution medium.
- Figure 3 is the dissolution curve of the pharmaceutical composition of the present invention using pH 4.0 acetate buffer salt as the dissolution medium.
- Figure 4 is the dissolution curve of the pharmaceutical composition of the present invention using pH 6.8 phosphate buffer salt as the dissolution medium.
- the present invention provides an antiarrhythmic pharmaceutical composition with good stability and rapid dissolution and a preparation method thereof.
- the phosphate of compound A (hereinafter referred to as compound B), lactose, microcrystalline cellulose, and pregelatinized starch were granulated by wet granulation according to the proportions in Table 1, with 3% hypromellose (50cp) 60% ethanol
- the solution is a binder, granulation and drying are performed, and then the dry granules (moisture less than 3%) are granulated, and then the prescribed amount of croscarmellose sodium and magnesium stearate are added for mixing and mixing.
- the tablets are compressed, and the tablets are compressed according to the standard of 100 mg of compound B per tablet to obtain the product.
- the dissolution rate is determined by the second method (pulp method) of the dissolution rate determination in accordance with the fourth appendix 0931 of the Chinese Pharmacopoeia 2015 edition using 1000ml of 0.01mol/L hydrochloric acid solution (the same below).
- Compound B lactose, microcrystalline cellulose, and pregelatinized starch were granulated by wet granulation according to the proportions in Table 2, using 3% hypromellose (50cp) and 60% ethanol solution as binder for granulation ⁇ Drying treatment, then the dry granules (moisture less than 3%) are sized, then the prescription amount of croscarmellose sodium and magnesium stearate are added, mixed, after mixing, press the tablet, according to each tablet Standard compressed tablets containing 100mg of compound A are available.
- Prescriptions 10 and 11 contain high lactose, the prepared granules are harder, the surface is rough, the granules of prescription 12-13 are uniform, the surface is flat and smooth, the dissolution rate of prescription 12 is higher, and the large proportion of pregelatinized starch affects the disintegration and dissolution, so Preferred prescription 12.
- Compound B lactose, microcrystalline cellulose, and pregelatinized starch were granulated by wet granulation according to the proportions in Table 3. Using 3% hypromellose (50cp) and 75% ethanol solution as the binder, the granulation was carried out ⁇ Drying treatment, then the dry granules (moisture less than 3%) are sized, and then add croscarmellose sodium/sodium carboxymethyl starch/crospovidone and magnesium stearate in Table 3. After mixing and mixing, press tablets according to the standard of 100mg of compound A per tablet.
- prescription 14 is preferred. On the basis of determining the disintegrant, the dosage of the filler is further screened.
- Compound B lactose, microcrystalline cellulose, and pregelatinized starch were granulated by wet granulation according to the proportions in Table 4. Using 3% hypromellose (50cp) and 75% ethanol solution as a binder, the granulation was carried out ⁇ Drying treatment, then the dry granules (moisture less than 3%) are sized, then croscarmellose sodium and magnesium stearate are added, and mixed, after mixing, according to the standard that each tablet contains 100mg of compound A Tablet.
- prescription 14 has good granule fluidity, tablet appearance, dissolution appearance, dissolution and stability, so prescription 14 is determined to be the preferred prescription.
- Adopt hot air circulation oven 50°C blast drying, turn the pellets every half an hour.
- Use a rapid moisture analyzer to measure the moisture of the particles. When the moisture is between 2.0% and 3.0%, the drying ends and the material is collected.
- tablet weight control the weight difference should be controlled within ⁇ 5.0%, and the friability: should be less than 0.7%.
- the weight gain of the coating is about 3%.
- Electromagnetic induction aluminum foil sealing machine seals, the aluminum seal is tight, and the appearance is neat and tidy.
- the dissolution curves of the 4 dissolution media are attached.
- This product uses 0.01mol/L hydrochloric acid solution, pH 4.0 acetic acid buffer salt and pH 6.8 phosphate buffer salt as the dissolution medium. It dissolves more than 85% in 15 minutes, and it dissolves close to 85% in 15 minutes with water.
- the nature of the raw materials of this product is relatively stable, the compatibility of the raw and auxiliary materials in the preparation is good, and the single impurity does not exceed 0.1%.
- the relevant substances of the 3 batches of preparations are in compliance with the regulations.
- Batch number batch 1; batch: 10,000 tablets; specification: 0.1g; packaging: oral solid medicinal high-density polyethylene bottle;
- Batch number batch 1; batch: 10,000 tablets; specification: 0.1g; packaging: oral solid medicinal high-density polyethylene bottle; inspection conditions: 40°C ⁇ 2°C, RH75% ⁇ 5%.
- Batch number batch 2; batch size: 10,000 tablets; specification: 0.1g; packaging: oral solid medicinal high-density polyethylene bottle; inspection conditions: 40°C ⁇ 2°C, RH75% ⁇ 5%
- Batch number batch 3; batch size: 10,000 tablets; specification: 0.1g; packaging: oral solid medicinal high-density polyethylene bottle; inspection conditions: 40°C ⁇ 2°C, RH75% ⁇ 5%
- Batch number batch 1; batch: 10,000 tablets; specification: 0.1g; packaging: oral solid medicinal high-density polyethylene bottle; inspection conditions: 30°C ⁇ 2°C, RH65% ⁇ 5%
- Batch number batch 2; batch size: 10,000 tablets; specification: 0.1g; packaging: oral solid medicinal high-density polyethylene bottle; inspection conditions: 30°C ⁇ 2°C, RH65% ⁇ 5%
- Batch number batch 3; batch size: 10,000 tablets; specification: 0.1g; packaging: oral solid high-density polyethylene bottles; inspection conditions: 30°C ⁇ 2°C, RH65% ⁇ 5%
Abstract
Description
成分 | 用量 |
化合物B | 43.6 |
乳糖 | 13.2 |
微晶纤维素 | 26.4 |
预胶化淀粉 | 13.2 |
交联羧甲基纤维素钠 | 2.9 |
成分 | 用量 |
化合物B | 43.6 |
乳糖 | 13.2 |
微晶纤维素 | 26.4 |
预胶化淀粉 | 13.2 |
交联羧甲基纤维素钠 | 2.9 |
羟丙甲纤维素 | |
硬脂酸镁 | 0.7 |
总计 | 100 |
Claims (10)
- 一种抗心律失常的药物组合物,其特征在于,所述药物组合物包括:活性成分,包括1-(3-甲磺酰胺基苄基)-6-甲氧基,7-苄氧基-1,2,3,4-四氢异喹啉或其药学上可接受的盐;辅料,包括基于组合物总重量的30%~80%的乳糖、微晶纤维素和预胶化淀粉。
- 根据权利要求1所述的药物组合物,其特征在于,所述乳糖、微晶纤维素和预胶化淀粉占组合物总重量的40%~60%。
- 根据权利要求1所述的药物组合物,其特征在于,所述乳糖、微晶纤维素和预胶化淀粉的重量比为1:1.8~2.2:0.9~1.1。
- 根据权利要求1所述的药物组合物,其特征在于,所述药物组合物还包括崩解剂;其中,所述崩解剂选自羧甲基淀粉钠、交联羧甲基纤维素钠、低取代羟丙基纤维素及交联聚维酮中的至少一种。
- 根据权利要求1所述的药物组合物,其特征在于,所述崩解剂含量选自基于组合物的总重量的1-30%,优选2.5~4%。
- 根据权利要求1所述的药物组合物,其特征在于,所述的药物组合物还包括润滑剂;其中,所述润滑剂选自硬脂酸镁、硬脂酸锌、山嵛酸甘油酯、月桂基硫酸钠、氢化植物油、微粉硅胶、滑石粉、胶态二氧化硅中的至少一种,优选硬脂酸镁和胶态二氧化硅中的至少一种;所述润滑剂含量选自基于组合物的总重量的0.5%~5%,优选0.7%。
- 根据权利要求1所述的药物组合物,其特征在于,所述药物组合物为所述活性成分和所述辅料经过包括混合制粒和干燥工序后得到的颗粒剂、片剂或胶囊剂。
- 根据权利要求1所述的药物组合物,其特征在于,所述的药物组合物还包括粘合剂,其中,所述粘合剂选自羟丙甲纤维素、羟丙基纤维素、羧甲基纤维素钠、聚乙烯吡咯烷酮,甲基纤维素中的至少一种;所述粘合剂含量选自基于组合物的总重量的0.5-10%,优选1.25%。
- 一种制备如权利要求1所述的药物组合物的方法,其特征在于,该方法包括:a)将活性成分与乳糖、微晶纤维素和预胶化淀粉混合过筛;b)进行湿法制粒;c)动态干燥;d)整粒,总混。
- 根据权利要求9所述的方法,其特征在于,所述药物组合物选自片剂时,该方法包括:按重量比43.6:13.2:26.4:13.2份称取1-(3-甲磺酰胺基苄基)-6-甲氧基,7-苄氧基-1,2,3,4-四氢异喹啉磷酸盐、乳糖、微晶纤维素和预胶化淀粉混匀后过80目筛;加入3%的羟丙甲纤维素的75%乙醇溶液制软材,过20目筛制粒;采用热风循环烘箱,50℃鼓风干燥;采用20目筛整粒;将整粒后的干颗粒,加入交联羧甲基纤维素钠2.9份和硬脂酸镁0.7份混合;压片。
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022558472A JP2023524625A (ja) | 2020-03-31 | 2021-03-08 | 抗不整脈薬物組成物および製造方法 |
KR1020227033080A KR20220145878A (ko) | 2020-03-31 | 2021-03-08 | 항부정맥의 약물 조성물 및 제조 방법 |
US17/912,163 US20230135963A1 (en) | 2020-03-31 | 2021-03-08 | Anti-arrhythmic pharmaceutical composition and preparation method therefor |
EP21781415.1A EP4129289A4 (en) | 2020-03-31 | 2021-03-08 | ANTIARRHYTHMIC PHARMACEUTICAL COMPOSITION AND METHOD FOR THE PRODUCTION THEREOF |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010246916.0A CN113456639B (zh) | 2020-03-31 | 2020-03-31 | 一种抗心律失常的药物组合物及制备方法 |
CN202010246916.0 | 2020-03-31 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021196982A1 true WO2021196982A1 (zh) | 2021-10-07 |
Family
ID=77866147
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2021/079508 WO2021196982A1 (zh) | 2020-03-31 | 2021-03-08 | 一种抗心律失常的药物组合物及制备方法 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20230135963A1 (zh) |
EP (1) | EP4129289A4 (zh) |
JP (1) | JP2023524625A (zh) |
KR (1) | KR20220145878A (zh) |
CN (1) | CN113456639B (zh) |
WO (1) | WO2021196982A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114404375A (zh) * | 2022-01-21 | 2022-04-29 | 武汉九珑人福药业有限责任公司 | 一种叶酸固体制剂及其原料组合物、制备方法和应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1566098A (zh) * | 2003-07-02 | 2005-01-19 | 上海医药工业研究院 | 一类异喹啉化合物及其盐的制备方法和应用 |
CN104693115A (zh) * | 2013-12-06 | 2015-06-10 | 上海医药工业研究院 | 手性四氢异喹啉的衍生物或其盐及其制备方法和用途 |
CN105362245A (zh) * | 2014-08-30 | 2016-03-02 | 山东中泰药业有限公司 | 含有索利那新的片剂组合物及其制备方法 |
US20190177277A1 (en) * | 2016-08-31 | 2019-06-13 | China State Institute Of Pharmaceutical Industry | Salt derivative of tetrahydroisoquinoline and crystalline thereof and preparation method therefore and application thereof |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3002005A1 (en) * | 2014-09-30 | 2016-04-06 | Molkerei Meggle Wasserburg GmbH & Co. Kg | Direct compression excipient based on lactose, cellulose and starch |
CN107778232B (zh) * | 2016-08-31 | 2021-05-28 | 上海医药工业研究院 | 一种四氢异喹啉的盐衍生物及其晶体的制备方法和应用 |
CN107793356B (zh) * | 2016-08-31 | 2021-07-27 | 上海医药工业研究院 | 一种四氢异喹啉的盐衍生物及其晶体的制备方法和应用 |
-
2020
- 2020-03-31 CN CN202010246916.0A patent/CN113456639B/zh active Active
-
2021
- 2021-03-08 US US17/912,163 patent/US20230135963A1/en active Pending
- 2021-03-08 EP EP21781415.1A patent/EP4129289A4/en active Pending
- 2021-03-08 WO PCT/CN2021/079508 patent/WO2021196982A1/zh unknown
- 2021-03-08 KR KR1020227033080A patent/KR20220145878A/ko unknown
- 2021-03-08 JP JP2022558472A patent/JP2023524625A/ja active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1566098A (zh) * | 2003-07-02 | 2005-01-19 | 上海医药工业研究院 | 一类异喹啉化合物及其盐的制备方法和应用 |
CN104693115A (zh) * | 2013-12-06 | 2015-06-10 | 上海医药工业研究院 | 手性四氢异喹啉的衍生物或其盐及其制备方法和用途 |
CN105362245A (zh) * | 2014-08-30 | 2016-03-02 | 山东中泰药业有限公司 | 含有索利那新的片剂组合物及其制备方法 |
US20190177277A1 (en) * | 2016-08-31 | 2019-06-13 | China State Institute Of Pharmaceutical Industry | Salt derivative of tetrahydroisoquinoline and crystalline thereof and preparation method therefore and application thereof |
Non-Patent Citations (1)
Title |
---|
PENG, SIXUN ET AL.: "Cardiovascular Drug Research: Structural Modification Based on Active Components from Traditional Chinese Medicine", JOURNAL OF CHINA PHARMACEUTICAL UNIVERSITY, vol. 30, no. 5, 31 December 1999 (1999-12-31), pages 396 - 400, XP055854536 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114404375A (zh) * | 2022-01-21 | 2022-04-29 | 武汉九珑人福药业有限责任公司 | 一种叶酸固体制剂及其原料组合物、制备方法和应用 |
CN114404375B (zh) * | 2022-01-21 | 2023-06-27 | 武汉九珑人福药业有限责任公司 | 一种叶酸固体制剂及其原料组合物、制备方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
US20230135963A1 (en) | 2023-05-04 |
CN113456639B (zh) | 2024-01-26 |
JP2023524625A (ja) | 2023-06-13 |
CN113456639A (zh) | 2021-10-01 |
KR20220145878A (ko) | 2022-10-31 |
EP4129289A1 (en) | 2023-02-08 |
EP4129289A4 (en) | 2024-05-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5401327B2 (ja) | 溶出性の改善された錠剤 | |
CN101005830B (zh) | 包含普拉克索或其可药用盐的延长释放片剂、其制备方法及用途 | |
EP3409272B1 (en) | Pharmaceutical composition comprising eltrombopag olamine, reducing sugar, and polymeric binder | |
CN102579381B (zh) | 盐酸胍法辛缓释制剂及其制备方法 | |
JPS6191118A (ja) | チアミン塩の顆粒,その製造法および錠剤 | |
JPH01501934A (ja) | メチルプレドニソロン/カルボキシメチルスターチナトリウム錠剤組成物 | |
WO2021196982A1 (zh) | 一种抗心律失常的药物组合物及制备方法 | |
CN103768063A (zh) | 一种盐酸莫西沙星药物组合物及其制备方法 | |
WO2017101858A1 (zh) | 环苄普林之延释剂型 | |
JP5787762B2 (ja) | コーティングフィルム、及びそれを用いた顆粒、錠剤 | |
CN103565773B (zh) | 一种盐酸普拉格雷的药物组合物 | |
CN107998097A (zh) | 一种含奥美沙坦酯的片剂及其制备方法 | |
CN109498587A (zh) | 盐酸鲁拉西酮片的制备方法 | |
US20180344648A1 (en) | Clobazam tablet formulation and process for its preparation | |
CN114272219A (zh) | 一种盐酸多奈哌齐片及其制备方法 | |
JP7271869B2 (ja) | レボセチリジン含有錠剤 | |
CN111358795A (zh) | 一种枸橼酸托法替布制剂及其制备方法 | |
CN110446701B (zh) | 一种2-氨基嘧啶类化合物的药用组合物及其制备方法 | |
JPWO2020111089A1 (ja) | 医薬組成物 | |
JP5159091B2 (ja) | 活性成分の溶出を徐放性に制御する固形製剤 | |
CN113116840B (zh) | 一种硫酸羟氯喹片的制备方法 | |
WO2020038434A1 (zh) | 一种2-氨基嘧啶类化合物的药用组合物 | |
CN116893086A (zh) | 一种靶向药甲磺酸伏美替尼片的模拟片及其制备方法 | |
JP3934150B1 (ja) | 固形製剤および製剤組成物 | |
CN116650426A (zh) | 一种盐酸左西替利嗪片及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21781415 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 20227033080 Country of ref document: KR Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2022558472 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2021781415 Country of ref document: EP Effective date: 20221031 |