HRP20190936T1 - Amorfni letermovir i njegove krute farmaceutske formulacije za oralnu primjenu - Google Patents
Amorfni letermovir i njegove krute farmaceutske formulacije za oralnu primjenu Download PDFInfo
- Publication number
- HRP20190936T1 HRP20190936T1 HRP20190936TT HRP20190936T HRP20190936T1 HR P20190936 T1 HRP20190936 T1 HR P20190936T1 HR P20190936T T HRP20190936T T HR P20190936TT HR P20190936 T HRP20190936 T HR P20190936T HR P20190936 T1 HRP20190936 T1 HR P20190936T1
- Authority
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- Croatia
- Prior art keywords
- letermovir
- solid pharmaceutical
- pharmaceutical formulation
- hcmv
- amorphous state
- Prior art date
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- FWYSMLBETOMXAG-QHCPKHFHSA-N letermovir Chemical compound COC1=CC=CC(N2CCN(CC2)C=2N([C@@H](CC(O)=O)C3=CC=CC(F)=C3N=2)C=2C(=CC=C(C=2)C(F)(F)F)OC)=C1 FWYSMLBETOMXAG-QHCPKHFHSA-N 0.000 title claims 22
- 229950010668 letermovir Drugs 0.000 title claims 22
- 239000008194 pharmaceutical composition Substances 0.000 title claims 13
- 239000007787 solid Substances 0.000 title claims 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 12
- 238000000034 method Methods 0.000 claims 9
- 206010011831 Cytomegalovirus infection Diseases 0.000 claims 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 4
- 241000701024 Human betaherpesvirus 5 Species 0.000 claims 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims 4
- 238000001556 precipitation Methods 0.000 claims 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- 238000004128 high performance liquid chromatography Methods 0.000 claims 3
- 239000002904 solvent Substances 0.000 claims 3
- 229920002785 Croscarmellose sodium Polymers 0.000 claims 2
- 241000701022 Cytomegalovirus Species 0.000 claims 2
- 102000004190 Enzymes Human genes 0.000 claims 2
- 108090000790 Enzymes Proteins 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 238000005119 centrifugation Methods 0.000 claims 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims 2
- 238000001514 detection method Methods 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 238000004090 dissolution Methods 0.000 claims 2
- 238000001914 filtration Methods 0.000 claims 2
- 239000012530 fluid Substances 0.000 claims 2
- 230000002496 gastric effect Effects 0.000 claims 2
- 238000002347 injection Methods 0.000 claims 2
- 239000007924 injection Substances 0.000 claims 2
- 238000002955 isolation Methods 0.000 claims 2
- 235000019359 magnesium stearate Nutrition 0.000 claims 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 2
- 229940069328 povidone Drugs 0.000 claims 2
- 239000000377 silicon dioxide Substances 0.000 claims 2
- 238000011282 treatment Methods 0.000 claims 2
- 208000030507 AIDS Diseases 0.000 claims 1
- 241000700586 Herpesviridae Species 0.000 claims 1
- 206010035664 Pneumonia Diseases 0.000 claims 1
- 206010035742 Pneumonitis Diseases 0.000 claims 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 150000001298 alcohols Chemical class 0.000 claims 1
- 238000007908 dry granulation Methods 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 239000003480 eluent Substances 0.000 claims 1
- 206010014599 encephalitis Diseases 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 claims 1
- 230000000968 intestinal effect Effects 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 238000004007 reversed phase HPLC Methods 0.000 claims 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 230000005748 tumor development Effects 0.000 claims 1
- 239000003643 water by type Substances 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
-
- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Biotechnology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (15)
1. Letermovir prema formuli (I),
koji je u amorfnom stanju, dobavljiv postupkom taloženja za izoliranje amorfnog Letermovira, naznačen time što
taloženje spomenutog amorfnog Letermovira iz otapala koja se mogu miješati s vodom acetona ili acetonitrila u suvišak miješane vode, nakon izolacije pomoću filtracije ili centrifugacije dobivenog Letermovira.
2. Letermovir prema zahtjevu 1, pri čemu spomenuti postupak ima naknadni korak sušenja in vacuo.
3. Letermovir prema bilo kojem od zahtjeva 1 i 2, pri čemu spomenuti Letermovir u amorfnom stanju nije izoliran taloženjem koristeći alkohole, posebno metanol ili etanol ili koristeći THF ili MEK.
4. Letermovir prema bilo kojem od zahtjeva 1 do 3, pri čemu je dobiveni Letermovir procesiran suhom granulacijom.
5. Kruta farmaceutska formulacija koja sadrži Letermovir u amorfnom stanju, pri čemu je spomenuta kruta farmaceutska formulacija oralno primjenjiva.
6. Kruta farmaceutska formulacija prema zahtjevu 5, koja sadrži Letermovir u amorfnom stanju kako je definirano u bilo kojem od zahtjeva 1 do 4.
7. Kruta farmaceutska formulacija prema zahtjevima 5 ili 6, koja nadalje sadrži povidon, kroskarmeloza natrij, mikrokristalnu celulozu, koloidnu bezvodnu siliku i magnezij stearat.
8. Kruta farmaceutska formulacija prema zahtjevu 7, pri čemu je spomenuti Letermovir u amorfnom stanju sadržan u količini od 30.0 % do 50.0 % (w/w), spomenuti povidon je sadržan u količini od 2.0 % do 10.0 % (w/w), spomenuti kroskarmeloza natrij je sadržan u količini od 2.0 % do 10 % (w/w), spomenuta mikrokristalna celuloza je sadržana u količini od 20.0 % do 70.0 % (w/w), spomenuta koloidna bezvodna silika je sadržana u količini od 0.5 % do 5.0 % (w/w) i spomenuti magnezij stearat je sadržan u količini od 0.1 % do 5.0 % (w/w).
9. Kruta farmaceutska formulacija prema zahtjevima 5 do 8, koja je efikasna u postizanju apsolutne biodostupnosti od 70 % ± 30 % Letermovira kada je primijenjena oralno u spomenutoj formulaciji koja sadrži barem 5 mg Letermovira u amorfnom stanju.
10. Kruta farmaceutska formulacija prema bilo kojem od zahtjeva 5 do 8, pri čemu spomenuti Letermovir u amorfnom stanju pokazuje disoluciju od > 50 % unutar 30 minuta, poželjno > 60 % unutar 30 minuta, poželjnije > 70 % unutar 30 minuta, još poželjnije > 80 % unutar 30 minuta, najpoželjnije > 90 % unutar 30 minuta, testirajući disoluciju Letermovira u amorfnom stanju prema Ph. Eur. metodi 2.9.3, Aparatura 2, uz brzinu vesla od 50 rpm pri 37.0 °C ± 0.5 °C u 1000 ml 0.1 N HCl / 0.2 % natrij lauril sulfat medija i mjereći pomoću HPLC reverzne faze u točci vremena na 30 minuta kako slijedi:
HPLC operacijski uvjeti:
Kolona: Waters Symmetry Nucleosil 100 C18, 40 mm x 4.0 mm, 10 µm
Valna duljina detekcije: 256 nm
Dužina trajanja otprilike: 4 minute
Dužina zadržavanja otprilike: 1.3 minute
Temperatura kolone: 40 °C
Volumen injekcije: 20 µL
Brzina protoka: 1.5 ml/min
Mobilna faza: Pufer pH 4.0/Acetonitril; 55/45 v/v.
11. Kruta farmaceutska formulacija prema bilo kojem od zahtjeva 5 do 10, pri čemu je spomenuta kruta farmaceutska formulacija formulacija s trenutnim otpuštanjem, naznačena time što se ne manje od 85 % količine Letermovira u amorfnom stanju otapa unutar 30 min koristeći USP Aparaturu I pri 100 rpm ili USP Aparaturu II pri 50 rpm u volumenu od 900 ml ili manje od svakog od sljedećih medija:
(1) kiseli medij, poput USP simulirane želučane tekućine bez enzima;
(2) pH 4.5 pufer; i
(3) pH 6.8 pufer ili USP-simulirana crijevna tekućina bez enzima.
12. Kruta farmaceutska formulacija prema bilo kojem od zahtjeva 5 do 11, pri čemu spomenuti Letermovir u amorfnom stanju pokazuje kemijsku stabilnost od barem 36 mjeseci tijekom pohrane pri sobnoj temperaturi (25 °C) i (60 %) relativnoj vlažnosti, određeno HPLC-om reverzne faze kako slijedi:
HPLC operacijski uvjeti:
Kolona: Intertsil ODS III 5 µm ili ekvivalentna
Otapalo: Acetonitril/0.1 N HCl; 3 + 7 (v/v)
Eluens A: Voda, pH 2.40; B: Acetonitril
Valna duljina detekcije: 235 nm
Temperatura kolone: 40 °C
Volumen injekcije: 15 µL
Brzina protoka: 1.0 ml/min
Dužina trajanja: 30 minuta.
13. Kruta farmaceutska formulacija prema bilo kojem od zahtjeva 5 do 12, za uporabu u postupku profilakse ili postupku liječenja za bolesti povezane sa skupinom Herpesviridae, poželjno povezane s citomegalovirusom (CMV), još poželjnije povezane s humanim citomegalovirusom (HCMV).
14. Kruta farmaceutska formulacija prema zahtjevu 13, za uporabu u postupku profilakse ili postupku liječenja za bolesti odabrane iz skupine koja sadrži HCMV zaraze kod subjekta, posebno HCMV zaraze kod subjekta koji ima AIDS, HCMV-pneumonitis, HCMV-encefalitis, kao i gastrointestinalne i sistemske HCMV zaraze, HCMV zaraze kod novorođenčadi i djece, akutne HCMV zaraze kod trudnih žena, HCMV zaraze u pacijentima potisnutog imunološkog sustava s rakom, HCMV-pozitivne pacijente s rakom kako bi se adresirao HCMV-posredovani razvoj tumora.
15. Postupak dobivanja amorfnog Letermovira, spomenuti postupak sadrži taloženje spomenutog amorfnog Letermovira iz otapala koja se mogu miješati s vodom acetona ili acetonitrila u suvišak miješane vode, nakon izolacije pomoću filtracije ili centrifugacije dobivenog Letermovira.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13003120 | 2013-06-19 | ||
| EP14165027 | 2014-04-16 | ||
| PCT/EP2014/062974 WO2014202737A1 (en) | 2013-06-19 | 2014-06-19 | Amorphous letermovir and solid pharmaceutical formulations thereof for oral administration |
| EP14732545.0A EP3010891B1 (en) | 2013-06-19 | 2014-06-19 | Amorphous letermovir and solid pharmaceutical formulations thereof for oral administration |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20190936T1 true HRP20190936T1 (hr) | 2019-10-04 |
Family
ID=50982905
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20190936TT HRP20190936T1 (hr) | 2013-06-19 | 2019-05-21 | Amorfni letermovir i njegove krute farmaceutske formulacije za oralnu primjenu |
Country Status (34)
| Country | Link |
|---|---|
| US (1) | US10442773B2 (hr) |
| EP (1) | EP3010891B1 (hr) |
| JP (2) | JP6445546B2 (hr) |
| KR (1) | KR101953270B1 (hr) |
| CN (1) | CN105555771A (hr) |
| AU (1) | AU2014283231B2 (hr) |
| BR (1) | BR112015031979B1 (hr) |
| CA (1) | CA2916143C (hr) |
| CU (1) | CU24619B1 (hr) |
| CY (1) | CY1121732T1 (hr) |
| DK (1) | DK3010891T3 (hr) |
| DO (1) | DOP2015000303A (hr) |
| EA (1) | EA036131B1 (hr) |
| ES (1) | ES2730958T3 (hr) |
| HK (1) | HK1223935A1 (hr) |
| HR (1) | HRP20190936T1 (hr) |
| HU (1) | HUE043721T2 (hr) |
| IL (2) | IL243228B (hr) |
| LT (1) | LT3010891T (hr) |
| MD (1) | MD4673C1 (hr) |
| ME (1) | ME03483B (hr) |
| MX (1) | MX2015017758A (hr) |
| MY (1) | MY179502A (hr) |
| NZ (1) | NZ715387A (hr) |
| PE (1) | PE20160659A1 (hr) |
| PH (1) | PH12015502821B1 (hr) |
| PL (1) | PL3010891T3 (hr) |
| PT (1) | PT3010891T (hr) |
| RS (1) | RS58882B1 (hr) |
| SG (1) | SG11201510426PA (hr) |
| SI (1) | SI3010891T1 (hr) |
| UA (1) | UA117755C2 (hr) |
| WO (1) | WO2014202737A1 (hr) |
| ZA (1) | ZA201509239B (hr) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10319612A1 (de) * | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| DE102012101673A1 (de) | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| DK3010891T3 (da) * | 2013-06-19 | 2019-06-24 | Aicuris Anti Infective Cures Gmbh | Amorf letermovir og faste farmaceutiske formuleringer deraf til oral indgivelse |
| JPWO2017170858A1 (ja) | 2016-03-31 | 2019-02-14 | インターセプト ファーマシューティカルズ， インコーポレイテッド | 溶出性に優れた経口製剤 |
| CA3132741A1 (en) * | 2019-03-12 | 2020-09-17 | Microbiotix, Inc. | Combination drug treatment for human cytomegalovirus |
| CN111024861A (zh) * | 2019-12-31 | 2020-04-17 | 山东省药学科学院 | 一种莱特莫韦及含莱特莫韦的制剂中有关物质的检测方法 |
| EP3906929A1 (en) | 2020-05-08 | 2021-11-10 | AiCuris GmbH & Co. KG | Letermovir for use in the prevention and the treatment of coronavirus infections |
| US20230312485A1 (en) | 2020-08-17 | 2023-10-05 | Lupin Limited | A precipitation process for amorphous letermovir |
| US20240041882A1 (en) * | 2020-12-16 | 2024-02-08 | Merck Sharp & Dohme Llc | Mini-tablet dosage form of a viral terminase inhibitor and uses thereof |
| CN115403528A (zh) * | 2021-05-27 | 2022-11-29 | 南京正大天晴制药有限公司 | 无定形3,4-二氢喹唑啉衍生物的制备方法 |
| CN114942278B (zh) * | 2022-04-12 | 2023-09-08 | 山东诚创蓝海医药科技有限公司 | 来特莫韦中间体二d-(+)-二对甲基苯甲酰酒石酸乙酸乙酯络合物有关物质的分析方法 |
| WO2024037485A1 (zh) * | 2022-08-15 | 2024-02-22 | 上海迪赛诺化学制药有限公司 | 一种来特莫韦无定形的制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10207026A1 (de) * | 2002-02-20 | 2003-08-28 | Boehringer Ingelheim Kg | Pulverinhalativum, enthaltend den CGRP-Antagonisten BIBN4096 und Verfahren zu dessen Herstellung |
| DE10319612A1 (de) * | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| DE10305785A1 (de) * | 2003-02-12 | 2004-08-26 | Bayer Healthcare Ag | Dihydrochinazoline |
| DE10338402A1 (de) * | 2003-08-18 | 2005-03-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Sprühgetrocknetes, amorphes BIBN 4096, Verfahren zu dessen Herstellung sowie dessen Verwendung als Inhalativum |
| CA2604735A1 (en) * | 2005-04-12 | 2006-10-19 | Elan Pharma International Limited | Nanoparticulate quinazoline derivative formulations |
| DE102005027517A1 (de) * | 2005-06-15 | 2006-12-21 | Bayer Healthcare Ag | Verfahren zur Herstellung von Dihydrochinazolinen |
| MX2013012771A (es) * | 2011-05-04 | 2013-11-21 | Merck Sharp & Dohme | Proceso para la preparacion de inhibidores del virus de la hepatitis c. |
| DE102012101659A1 (de) * | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| DE102012101673A1 (de) * | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| DE102012101680A1 (de) * | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Pharmazeutische Zubereitung enthaltend ein antiviral wirksames Dihydrochinazolinderivat |
| WO2014047562A2 (en) * | 2012-09-21 | 2014-03-27 | Epiphany Biosciences | Method of treating and/or preventing shingles and method of treating and/or preventing zoster associated pain |
| DK3010891T3 (da) * | 2013-06-19 | 2019-06-24 | Aicuris Anti Infective Cures Gmbh | Amorf letermovir og faste farmaceutiske formuleringer deraf til oral indgivelse |
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