WO2015163724A1 - Agent antiviral sous forme solide et son procédé de préparation - Google Patents

Agent antiviral sous forme solide et son procédé de préparation Download PDF

Info

Publication number
WO2015163724A1
WO2015163724A1 PCT/KR2015/004101 KR2015004101W WO2015163724A1 WO 2015163724 A1 WO2015163724 A1 WO 2015163724A1 KR 2015004101 W KR2015004101 W KR 2015004101W WO 2015163724 A1 WO2015163724 A1 WO 2015163724A1
Authority
WO
WIPO (PCT)
Prior art keywords
free base
crystalline
present
ethanol
isopropanol
Prior art date
Application number
PCT/KR2015/004101
Other languages
English (en)
Korean (ko)
Inventor
지준홍
유형철
김재선
엄기안
이정범
이보람
Original Assignee
지준홍
제이투에이치바이오텍 (주)
주식회사 휴온스
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=54246792&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2015163724(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by 지준홍, 제이투에이치바이오텍 (주), 주식회사 휴온스 filed Critical 지준홍
Publication of WO2015163724A1 publication Critical patent/WO2015163724A1/fr

Links

Classifications

    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C07D473/34—Nitrogen atom attached in position 6, e.g. adenine

Definitions

  • Antiviral agent in solid form and preparation method thereof is an antiviral agent in solid form and preparation method thereof
  • the present invention relates to a novel crystalline form of tenofovirisoproxyl free base and a process for preparing the same.
  • Tenofovirdisopoxyfumarate (trade name Viread, hereinafter TenenofovirDisoproxilFumarate) has the chemical name 9- [2— (R) ⁇
  • Tenofodisodixoxyfumarate has a molecular weight of 635.52 and is represented by the following structural formula ().
  • Tenofovirodisulfoxyfumarate is a nucleotide analog reverse transcriptase and HBV polymerase inhibitor, as determined by Giliard Science. It is developed and marketed under the trade name Vi read, and is a useful drug for the treatment of HIV-1 infection and chronic hepatitis B.
  • Tenofovirisofufosilfumarate is an crystalline solid and has an endothermic peak of about 118 ° as measured in DSC (Di f ierental scanning calorimetry) as described in the prior publications WO099 / 05150 and EP998480.
  • Tenofovirisofufocilfumarate is known to have a variety of crystal polymorphs, and the transition of the crystal form may occur due to formulation preparation and change over time. On the other hand, it is known that tenofovirisoproxyl has a problem in stability due to the influence of moisture.
  • tenofovirodisotoxyl When tenofovirodisotoxyl is reacted in the form of an oil to obtain a salt or to proceed with a salt formation reaction without obtaining a salt (i so l at i on), various problems may occur.
  • tenofovirisoproxil in oil form has problems of stability, difficulty in controlling equivalent weight according to salts and exact molar ratio, and difficulty in strictly managing below-standard flexible compounds of acid addition salts. There is this. For example, excess organic acid may be precipitated and mixed during salt formation. It is likely that the drug does not meet the requirements for leaded substances in pharmaceuticals that require strict control standards.
  • United States Patent Application Publication No. 2011/0112292 discloses a method for preparing a crystalline tenofovirosophyxyl free base to solve this problem; It presents a novel crystal form, and a method of producing with a melting point in C to 66 'C.
  • the present invention also has the usefulness of crystalline tenofovirisophoxyl as an intermediate for preparing tenofovirisophthoxyfumarate To emphasize.
  • Published Patent Publication No. 2012-0095874 discloses a novel salt of tenofovirisoproxyl and a method for preparing the same, and also discloses a method of obtaining a free base from tenofovirdisofoxyl fumarate.
  • the free base disclosed in the present invention ethyl acetate is added to the fumarate, and the resultant is solidified by stirring with sodium bicarbonate, followed by drying and concentration.
  • the free base disclosed in this invention was used as a raw material for preparing aspartate, which is a crystalline acid addition salt, instead of being used as a drug substance.
  • the present inventor's stone is a sticky solid having a melting point formed at 94-97 ° C., resulting in an uneven particle size distribution.
  • adhesion becomes a problem, stability and hygroscopicity are poor, and purity products required for the drug substance are not obtained. It was required, and the amount of residual solvent after drying did not conform to the ICH (International Standard) standard, and thus could not be used as a pharmaceutical raw material.
  • ICH International Standard
  • the present inventors have a thermodynamically stable and hygroscopicity, and thus can be stored for a long time at room temperature, and they are not sticky and have excellent solubility. I want to.
  • the present inventors have attempted to obtain a novel crystalline free base of tenofovirisopropyl having excellent physicochemical properties and stability while overcoming the drawbacks of the conventional tenofovirisophyxyl fumarate.
  • the present inventors have developed a method and conditions capable of preparing a new crystalline form of tenofovirisoproxyl free base having the above-mentioned advantages, and thus the tenofovirisoproxyl freebase prepared is thermodynamically It was found to be stable and, by itself, of high purity suitable for use as an active ingredient in pharmaceuticals. Accordingly, it is an object of the present invention to provide a novel crystalline tenofovirodisoxyl free base.
  • Another object of the present invention is to provide an antiviral pharmaceutical composition comprising the above-mentioned crystalline tenofovirodisoxyl free base of the present invention.
  • the present invention has a positive peak diffraction angle (2 ⁇ ⁇ 0. ⁇ ) in an X-ray diffraction (PXRD) analysis of 7.4 ⁇ 0.2 ° , 8.1 ° 0.2 ° , 10.8 ⁇ 0.2 ° ,
  • the present inventors have attempted to obtain a novel crystalline free base of tenofovirisophoxyl having excellent purity, excellent physicochemical properties, and stability while overcoming the disadvantages of the conventional tenofovirdisopoxylfumarate.
  • the present inventors have developed a method and conditions capable of preparing a new crystalline form of tenofovirisoproxyl free base having the above-mentioned advantages, and thus the tenofovirisoproxyl free base is thermodynamically stable, It was found to be suitable for use as an active ingredient of medicines by themselves.
  • the crystalline tenofovirodisoficyl freebase of the present invention represented by the formula (2) exhibits an X-ray diffraction pattern different from other known freebases.
  • the crystalline tenofovirodisoxyl free base of the present invention has the X-ray diffraction pattern shown in FIG. More specifically, the crystalline tenofovirosophyxyl free base of the present invention has a differential scanning calorimetry (DSC) characteristic of FIG. 2 and a melting point of 107 Pa 3 ° C.
  • DSC differential scanning calorimetry
  • the crystalline tenopovirdisopoxyl free base of the present invention is a conventional free base (e.g., US Patent Publication No. 2011/0112292 and Korean Patent Application Publication No.
  • the present invention provides a process for the preparation of crystalline tenofovirisoopoxyl free base comprising the following steps:
  • step (b) adding magnesium sulfate (MgSO 4 ) or sodium sulfate (Na 2 SO 4 ) as an absorbent and stirring the resultant of step (a); (c) filtering the resultant of step (b) and concentrating and drying under reduced pressure;
  • MgSO 4 magnesium sulfate
  • Na 2 SO 4 sodium sulfate
  • the manufacturing method of the present invention will be described in detail for each step as follows:
  • the step of dissolving or suspending tenofovirisoxolic acid addition salt in a mixed solvent of methylene chloride or methylene chloride and methanol, and adjusting the pH by adding an aqueous solution of sodium carbonate or sodium hydrogen carbonate to separate the organic layer by extraction Include.
  • the treatment of the aqueous sodium carbonate or sodium bicarbonate solution and the mixed solvent of methylene chloride or methylene chloride and methanol added to tenofovirisoxolate acid addition salt is not restricted in that order.
  • Tenofovirosophyxyl acid addition salts used in the present invention include various acid addition salts of tenofovirisoproxyl, for example, tenofovirisoxofumarate can be used.
  • step (b) magnesium sulfate (MgS0 4 ) or sodium sulfate (Na 2 S0 4 ) is added to the moisture absorbent and stirred to remove water.
  • step (c) the resultant is preferably filtered at 5 ° C., concentrated under reduced pressure and dried at 50 ° C. or lower.
  • step (c) To the product of step (c) or to the starting material of step (a) (ii), ethanol or isopropanol and a co-solvent of the two solvents are added and vigorous stirring and optional seeding as necessary. To obtain a crystalline tenofovirisoopoxyl free base.
  • Ethanol or isoprapan and the mixing ratio of the two solvents can be prepared in various ways, and the amount of the solvent used is 10-50 ml with respect to 1 g of tenofovirdisopoxyl free base.
  • the tenofovirodixosiloxane crystalline free base according to the present invention can be selectively seeded to speed up the precipitation time of the crystal. Seeding is not essential but is effective when no crystalline solid is precipitated after several hours of stirring.
  • the invention provides a process for the preparation of crystalline tenofovirisotropoxyl bases comprising the following steps:
  • step (c) obtaining the crystalline tenofovirosophyxyl free base through selective seeding of the resultant of step (b). .
  • the manufacturing method of the present invention will be described in detail for each step as follows:
  • tenofovirisoproxyl freebases mucous oils or amorphous and crystalline solids
  • mucous free bases or amorphous and other forms of crystalline freebases for example, Korean Laid-Open Patent Publication No. 2012-0095874.
  • Step (c): ⁇ of the crystalline tenofovirodisoxyl free base by recrystallization for crystallization of the result of steps (a)-(b). Violent stirring and optionally seeding as necessary yields a crystalline tenofovirisotropoxyl freebase.
  • the present invention provides a pharmaceutical composition for anti-viral comprising the above-mentioned crystalline tenofovirodisofoxyl free base of the present invention.
  • the virus is human immunodeficiency virus (HIV) -1 or hepatitis B virus (HBV).
  • HIV human immunodeficiency virus
  • HBV hepatitis B virus
  • the composition of the present invention is a drug useful for the treatment of HIV-1 infection and chronic hepatitis B.
  • the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier.
  • Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are commonly used in the preparation, lactose, dextrose, sucrose, sorbbi, manny, starch, acacia rubber, calcium phosphate, alginate, Gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil Including, but not limited to.
  • the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives , and the like, in addition to the above components.
  • lubricants wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives , and the like.
  • suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).
  • the pharmaceutical composition of the present invention can be administered to various mammals such as oral or parenteral to mammals such as rats, mice, livestock, humans, and in the case of parenteral administration, intravenous injection, subcutaneous injection, intramuscular injection, abdominal cavity Administration by infusion, transdermal administration, or the like.
  • Suitable dosages of the pharmaceutical compositions of the present invention will vary depending on factors such as the formulation method, mode of administration, age, weight, sex, pathological condition, food, time of administration, route of administration, rate of excretion and reaction in response to the patient. It may be prescribed.
  • the daily dose of the pharmaceutical composition of the present invention is, for example, 0.01-100 mg / kg.
  • the pharmaceutical compositions of the present invention may be prepared in unit dosage form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporation into a multi-dose container.
  • the formulation may be used in any form suitable for pharmaceutical preparations, including powders, granules, tablets, capsules, suspensions, oral formulations such as emulsions, syrups, aerosols, external preparation suppositories such as ointments and creams, and sterile injectable solutions. It may further comprise a dispersant or stabilizer. ⁇ Effects of the Invention ⁇
  • the features and advantages of the present invention are summarized as follows: (a)
  • the tenofovirosophyxyl free base according to the present invention can minimize the generation of a flexible material with the change over time, compared to tenofovirisoofoxyl fumarate, lowering the amount of impurities generated during the storage of the product, the stability of the formulation Can increase.
  • the tenofovirosophyloxy free base according to the present invention can be produced with much better Sejo purity (pur i ty) compared to the known tenofovirisophyxyl free base.
  • the tenofovirodisoxyl free base according to the present invention has excellent physicochemical properties such as hygroscopicity, solubility, and adhesiveness, so that it can be used as a useful active ingredient of a pharmaceutical composition.
  • Tenofovirosophyxyl free base according to the present invention is industrially useful because it is suitable for high yield and high purity, the specification of the flexible material and residual solvent as a pharmaceutical raw material. [Brief Description of Drawings]
  • FIG. 1 is a view showing an X-ray diffraction pattern of the tenofovirosophyxyl free base crystal form according to the present invention.
  • FIG. 2 is a diagram showing a DSC (Di f ferent i Al scanni ng cal or imet ry) record of the tenofovirisoproxyl free base crystal form according to the present invention.
  • DSC Di f ferent i Al scanni ng cal or imet ry
  • Fig. 3 shows the X-ray diffraction pattern (top) of the tenofovirosophyxyl free base crystalline form of the present invention and the X-ray diffraction pattern (bottom) of the glass base prepared by the method described in Korean Laid-Open Patent Publication No. 10-2014-0028790. Are diagrams comparing each.
  • FIG. 4 is a diagram showing the DSC data of tenofovirosophyloxy free base crystalline form (green graph) and tenofovirosophyloxy free base (blue graph) of JP 10-2014-0028790 of the present invention. .
  • FIG. 5 is a view showing a particle diagram of the tenofovirosophyxyl free base of the present invention.
  • FIG. 6 is a view showing a particle diagram of a free base described in Patent Publication No. 10—2014-0028790.
  • Figure 7 is a view showing a comparison of the powder picture of the free base (left) and the tenofovirsoxotoxyl free base of the present invention (right) according to the invention described in Korea Patent Publication No. 10-2014-0028790. While the glass base according to Korean Patent Laid-Open Publication No. 10-2014- 0028790 is strong and agglomerated, the tenofoviroxoxyl free base according to the present invention shows the form of a homogeneous powder.
  • Example 1 Tenofovirosophyroxyl Free Base Novel Crystalline Production Phase 200 g of tenofovirisofluorofumalate (China Asta chemical) was dissolved in 3.6 L of methylene chloride and 360 ml of methanol. An aqueous 10% sodium carbonate solution was added thereto, stirred for 10 minutes, the pH was adjusted to about 9-10, and the organic layer was separated. Magnesium sulfate was used to remove water from the organic worms, and the filtrate was concentrated under reduced pressure at 45 ° C. Thereafter, 600 ml of isopropyl alcohol was added thereto, followed by stirring at 24 ° C.
  • phase silver 100 g of tenofovirdisoficylpydolate was dissolved by adding 1.8 L of methylene chloride and 180 ml of methanol. Thereafter, the prepared 10% aqueous sodium carbonate solution was added thereto, stirred for 10 minutes, the pH was adjusted to about 9-10, and the organic layer was separated. Water was removed from the organic layer using magnesium sulfate, filtered and concentrated under reduced pressure at 45 ° C. After that 300 ml of ethane was added, followed by stirring at 24 ° C.
  • 10-2014-0028790 was added 300 ml of isopropyl alcohol and 300 ml of ethanol, and then at 24 ° C. Stir vigorously for 4 hours, and then filter (wash 200 ml of isopropyl alcohol) to give 95 g of tenofovirodisoxyl base novel crystalline form (melting point (mp): 106 ° C., Purity: 99.93%).
  • X-ray powder diffraction pattern is widely used to differentiate crystalline forms and hydrates of a unique characteristic of the drug. Therefore, the X-ray powder pattern of the tenofovirisophyxyl free base of this invention was measured.
  • Powder X-ray diffraction (PXRD) analysis of a new crystalline form of tenofobicisoproxyl free base showed that the 2 ⁇ diffraction angle was 7.4 ⁇ 0.2 ° , 8.1 ⁇ 0.2 ° , 10.8 ⁇ 0.2 ° , 13 ° 0.2 ° , 14.4 ⁇ 0.2 °, 14.8 ⁇ 0.2 ° , 16.2 ⁇ 0.2 ° , 16.7 ⁇ 0.2 °, 17.6 ⁇ 0.2 °, 18.04 ⁇ 0.2 °, 19.19 ⁇ 0.2 °, 19.4 ⁇ 0.2 °, 20.9 ⁇ 0.2 °, 22.9 ⁇ 0.2 °, 24.4 ⁇ 0.2 ° , Specific peaks were
  • the value of the powder X-ray diffraction (PXRD) angle of the novel tenofovirisoxoyl free base crystalline form shows a diffraction angle different from that of the tenofovirosomal free base of US Patent Publication No. 2011/0112292. Bar, it was confirmed that it is a new crystalline form.
  • PXRD powder X-ray diffraction
  • the upper graph is the tenofovirisoproxyl free base of the present invention
  • the lower graph is the data of the free base described in Korean Laid-Open Patent Publication No. 10-2014-0028790.
  • Experimental Example 2 Analysis of Differential Scanning Calorimetry (DSC) of a Novel Tenofobidisoproxyl Free Base
  • Thermodynamically ' stable because it has a melting point above 100 ° C, It is also good to use as an active ingredient of medicines, there is also an advantage in the preparation of acid addition salts, such as tenofovirisoproxyl.
  • DSC measurement results of the salt prepared in Korean Patent Application Laid-Open No. 10-2014-0028790 were 95 degrees and the endothermic peak was different from the crystalline form of the present invention and was not a thermodynamically stable crystalline form.
  • the stability test of a drug is to set the storage period and the period of use of the drug, and to set the expiration date by determining the significant change based on the specified test method after setting the appropriate standard. Is one of the most important factors in the commercialization of drugs.
  • ICH guide using crystalline tenofovirisoxofucil fumaric acid (Ast a chem i ca ls, ch i na) as a control Acceleration and harsh stability were performed along the line and analyzed using Liquid Chromatography (HPLC) analysis described in the USP. The results are shown in Tables 1 and 2.
  • the tenofovirisotropylic free base having the novel crystalline form represented by the present invention is a tenophoreodisopropyl fumaric acid or a control material under accelerated and harsh conditions. It can be seen that the material is very stable compared to the free base specified in 10-2014—0028790. In particular, the number of flexible materials and the increasing width is small, there is no problem to be affected by decomposition products that may occur during storage.
  • Tenofovirisopromonol ester (Tenofov irl sopropox il monoester), which is the main product of tenofovirisofluorofumarate, was 1.246% in case of tenofovirisofluorofumaric acid under severe conditions.
  • the increase in the amount of the decomposition product is 0.1% or less. Significantly improved.
  • Solubility for each pH was determined based on the solubility obtained under the above conditions.
  • the novel crystalline tenofovirisoproxyl free base made in the present invention has an equivalent degree of solubility in buffer solution for each pH compared to tenofovirodisoxylfumaric acid. Therefore, it can be seen that there is no difference in solubility according to the silvering effect between tenofovirisofumaric acid and tenofovirisofluorosilic acid base of the present invention.
  • Experimental Example 5 Comparative Evaluation of Hygroscopicity and Particle Size
  • the novel crystalline tenofovirodisoxyl glass base of the present invention shows a symmetrical particle distribution form with a narrow and narrow distribution, but the glass of Korean Patent Application Laid-Open No. 10-2014-0028790 In the case of a base, it has a particle distribution in the form of a pharmaceutical formulation with a wide variety of peaks.
  • the glass base (left) according to Korean Patent Laid-Open No. 10-2014-0028790 has a strong adhesiveness and agglomeration
  • the tenofovirsotoxyl glass base according to the present invention (right) ) Shows the form of a homogeneous powder.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une nouvelle forme cristalline de base libre de ténofovir disoproxil. La quantité de substances associées générées en fonction d'un laps de temps peut être minimisée dans la base libre de ténofovir disoproxil, selon la présente invention, par comparaison avec un fumarate de ténofovir disoproxil ou une base libre traditionnelle de ténofovir disoproxil, ce qui permet d'accroître la stabilité d'une préparation en réduisant la quantité d'impuretés générées dans un processus de stockage de produits. De plus, la nouvelle forme cristalline de la base libre de ténofovir disoproxil de la présente invention présente une meilleure hygroscopicité, une excellente solubilité en fonction du pH et d'excellentes propriétés physiques et chimiques, et peut être ainsi utilisée comme principe actif utile d'une composition pharmaceutique.
PCT/KR2015/004101 2014-04-25 2015-04-24 Agent antiviral sous forme solide et son procédé de préparation WO2015163724A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2014-0050011 2014-04-25
KR20140050011 2014-04-25
KR10-2014-0151114 2014-11-03
KR1020140151114A KR101548724B1 (ko) 2014-04-25 2014-11-03 고체 형태의 항바이러스제 및 이의 제조방법

Publications (1)

Publication Number Publication Date
WO2015163724A1 true WO2015163724A1 (fr) 2015-10-29

Family

ID=54246792

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2015/004101 WO2015163724A1 (fr) 2014-04-25 2015-04-24 Agent antiviral sous forme solide et son procédé de préparation

Country Status (2)

Country Link
KR (1) KR101548724B1 (fr)
WO (1) WO2015163724A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180214378A1 (en) * 2017-01-27 2018-08-02 Steerlife India Private Limited Tenofovir granules

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101669240B1 (ko) 2015-03-12 2016-10-25 아주대학교산학협력단 테노포비어 디소프록실 유리염기를 포함하는 정제 및 이의 제조방법
KR20220141457A (ko) 2021-04-13 2022-10-20 경동제약 주식회사 신규 결정형의 테노포비어 알라펜아미드 말레산염 및 이를 포함하는 약제학적 조성물

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101712692A (zh) * 2009-12-21 2010-05-26 巢杰 泰诺福韦酯的药用酸加成盐及其制备方法和药物应用
KR20110017863A (ko) * 2008-04-25 2011-02-22 씨아이피엘에이 엘티디. 테노포비어 디소프록실의 결정형 및 그의 제조방법
CN102240297A (zh) * 2005-06-13 2011-11-16 博瑞生物医药技术(苏州)有限公司 泰诺福韦的晶体
KR20140028790A (ko) * 2012-08-30 2014-03-10 주식회사 종근당 테노포비어 디소프록실의 신규염 및 그의 제조방법

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011111074A2 (fr) 2010-03-11 2011-09-15 Matrix Laboratories Ltd Procede perfectionne de preparation de tenofovir disoproxil fumarate

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102240297A (zh) * 2005-06-13 2011-11-16 博瑞生物医药技术(苏州)有限公司 泰诺福韦的晶体
KR20110017863A (ko) * 2008-04-25 2011-02-22 씨아이피엘에이 엘티디. 테노포비어 디소프록실의 결정형 및 그의 제조방법
CN101712692A (zh) * 2009-12-21 2010-05-26 巢杰 泰诺福韦酯的药用酸加成盐及其制备方法和药物应用
KR20140028790A (ko) * 2012-08-30 2014-03-10 주식회사 종근당 테노포비어 디소프록실의 신규염 및 그의 제조방법

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180214378A1 (en) * 2017-01-27 2018-08-02 Steerlife India Private Limited Tenofovir granules
US10561614B2 (en) * 2017-01-27 2020-02-18 Steerlife India Private Limited Tenofovir granules

Also Published As

Publication number Publication date
KR101548724B1 (ko) 2015-09-02

Similar Documents

Publication Publication Date Title
US8232293B2 (en) Crystalline forms of a potent HCV inhibitor
CN103626803B (zh) 替诺福韦二吡呋酯的固体及其制备方法和用途
JP2018524308A (ja) テノホビルアラフェナミドの共結晶、塩および結晶形態
WO2007013086A1 (fr) Nouveaux polymorphes de tenofovir disoproxil fumarate
US10351574B2 (en) Pharmaceutically acceptable salts and polymorphic forms of hydrocodone benzoic acid enol ester and processes for making same
WO2015163724A1 (fr) Agent antiviral sous forme solide et son procédé de préparation
CN111868057B (zh) 一种二氢嘧啶类化合物的固体形式及其制备方法和用途
US11230559B2 (en) Solid forms of [(1 S)-1 -[(2S,4R,5R)-5-(5-amino-2-oxo-thiazolo[4,5-D]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran-2-Yl]proptl] acetate
JP5642766B2 (ja) アデフォビルジピボキシルの新規結晶形及びその製造方法
KR20080048065A (ko) 다형 형태의 염산 레르카니디핀 및 이것의 제조방법
US12012421B2 (en) Solid forms of [(1S)-1-[(2S,4R,5R)-5-(5-amino-2-oxo-thiazolo[4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran-2-yl]propyl] acetate
US12012420B2 (en) Solid forms of [(1S)-1-[(2S,4R,5R)-5-(5-amino-2-oxo-thiazolo[4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran-2-yl]propyl] acetate
US11208382B2 (en) Entinostat-containing compound, crystal form of compound thereof, and preparation method therefor and pharmaceutical composition thereof
US11186599B2 (en) Phosphonamide ester compound, salt thereof, related crystal form thereof, preparation method therefor and use thereof
WO2015149270A1 (fr) Forme cristalline du semi-succinate de trélagliptine, sa méthode de préparation et sa composition pharmaceutique
WO2015109925A1 (fr) Forme cristalline de médicament contre l'hépatite c et son procédé de préparation, sa composition pharmaceutique et son utilisation
KR20130033243A (ko) 아데포비어 디피복실의 공결정

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: 15782225

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15782225

Country of ref document: EP

Kind code of ref document: A1