KR100613136B1 - 미셀-형성 계면활성제를 함유하는 에키노칸딘 제약학적조제물 - Google Patents
미셀-형성 계면활성제를 함유하는 에키노칸딘 제약학적조제물 Download PDFInfo
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- KR100613136B1 KR100613136B1 KR1020017011215A KR20017011215A KR100613136B1 KR 100613136 B1 KR100613136 B1 KR 100613136B1 KR 1020017011215 A KR1020017011215 A KR 1020017011215A KR 20017011215 A KR20017011215 A KR 20017011215A KR 100613136 B1 KR100613136 B1 KR 100613136B1
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- Prior art keywords
- echinocandine
- compound
- formulation
- preparation
- hydrogen
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- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
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- 239000003880 polar aprotic solvent Substances 0.000 description 1
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- 125000003367 polycyclic group Chemical group 0.000 description 1
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- FYGDTMLNYKFZSV-BYLHFPJWSA-N β-1,4-galactotrioside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@H](CO)O[C@@H](O[C@@H]2[C@@H](O[C@@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-BYLHFPJWSA-N 0.000 description 1
Classifications
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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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
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- A61P31/10—Antimycotics
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
Description
Claims (60)
- (i) 에키노칸딘 화합물 또는 제약학적으로 허용되는 그것의 염;(ii) 제약학적으로 허용되는 미셀-형성 계면활성제;(iii) 비독성 수성 용매; 및(iv) 안정제를 용액 중에 포함하는 안정화된 비경구적 제약학적 조제물로서,여기에서 상기 계면활성제가 1:1.75 내지 1:25의 에키노칸딘 화합물 대 미셀-형성 계면활성제의 중량비로 상기 조제물에 존재하고, 상기 에키노칸딘 화합물이 1mg/ml 내지 50mg/ml의 양으로 존재하고;상기 안정제는 탄수화물이고;상기 에키노칸딘 화합물은 다음 구조식 및 제약학적으로 허용되는 그것의 염으로 표시되고,상기 조제물은 용액인 것을 특징으로 하는 안정화된 비경구적 제약학적 조제물.상기식에서,R은 다음 구조식을 갖는 기이고;(상기식에서 A, B, C 및 D는 독립적으로 수소, C1-C12 알킬, C2-C12 알킨일, C1-C12 알콕시, C1-C12 알킬티오, 할로, 또는 -O-(CH2)m-[O-(CH2)n]p-O-(C1-C12알킬) 또는 -O-(CH2)q-X-E이고;m은 2, 3 또는 4이고;n은 2, 3 또는 4이고; p는 0 또는 1이고; q는 2, 3 또는 4이고;X는 피롤리디노, 피페리디노 또는 피페라지노이고;E는 수소, C1-C12 알킬, C3-C12 시클로알킬, 벤질 또는 C3-C12 시클로알킬메틸이다.)R1, R2, R3, R6, R7 및 R10은 독립적으로 히드록시 또는 수소이고;R4는 수소, 메틸 또는 -CH2C(O)NH2이고;R5 및 R11은 독립적으로 메틸 또는 수소이고;R8은 -OH, -OPO3H2, -OPO3HCH3, -OPO2HCH3 또는 -OSO3H이고;R9는 -H, -OH 또는 -OSO3H이다.
- 삭제
- 제 1 항에 있어서, 상기 미셀-형성 계면활성제가 폴리소르베이트, 폴리옥시에틸렌 피마자유 유도체, 폴리옥시에틸렌 스테아레이트, 소르비탄 트리올레에이트, 답즙산염, 레시틴 및 그것들의 조합으로 구성된 군으로부터 선택되는 것을 특징으로 하는 조제물.
- 제 1 항에 있어서, 상기 에키노칸딘 화합물이 1mg/ml 내지 40mg/ml의 양으로 존재하는 것을 특징으로 하는 조제물.
- 제 6 항에 있어서, 상기 에키노칸딘 화합물이 1 내지 30mg/ml의 양으로 존재하는 것을 특징으로 하는 조제물.
- 제 1 항에 있어서, 상기 계면활성제가 부피 당 1중량% 이상의 양으로 존재하는 것을 특징으로 하는 조제물.
- 제 1 항에 있어서, 에키노칸딘 대 계면활성제의 상기 중량비가 1:2 내지 1:3인 것을 특징으로 하는 조제물.
- 제 1 항에 있어서, 상기 용매가 물, 에탄올, 프로필렌 글리콜, 폴리에틸렌 글리콜 및 그것들의 혼합물로 구성된 군으로부터 선택되는 것을 특징으로 하는 조제물.
- 제 1 항에 있어서, 상기 안정제는 수크로스, 프럭토스, 트레할로스, 락토스 또는 그것들의 혼합물인 것을 특징으로 하는 조제물.
- 제 12 항에 있어서, 상기 안정제가 부피 당 0.5중량% 내지 10중량%의 양으로 존재하는 것을 특징으로 하는 조제물.
- 제 12 항에 있어서, 상기 안정제가 부피 당 1중량% 내지 6중량%의 양으로 존재하는 것을 특징으로 하는 조제물.
- 제 1 항에 있어서, 상기 안정제가 히스티딘, 리신, 글리신 및 그것들의 혼합물을 더 포함하는 것을 특징으로 하는 조제물.
- 제 1 항에 있어서, 완충액을 더 포함하는 것을 특징으로 하는 조제물.
- 제 16 항에 있어서, 상기 완충액이 아세테이트, 시트레이트, 타르트레이트, 락테이트, 숙시네이트, 포스페이트 및 아미노산으로 구성된 군으로부터 선택되는 것을 특징으로 하는 조제물.
- 제 1 항에 있어서, 등장제를 더 포함하는 것을 특징으로 하는 조제물.
- 제 18 항에 있어서, 상기 등장제가 글리세린, 락토스, 만니톨, 덱스트로스, 염화나트륨, 황산나트륨 및 소르비톨로 구성된 군으로부터 선택되는 것을 특징으로 하는 조제물.
- 제 18 항에 있어서, 상기 등장제가 1 내지 100mg/ml의 양으로 존재하는 것을 특징으로 하는 조제물.
- 제 18 항에 있어서, 상기 등장제가 9 내지 50mg/ml의 양으로 존재하는 것을 특징으로 하는 조제물.
- (i) 에키노칸딘 화합물 또는 제약학적으로 허용되는 그것의 염;(ii) 제약학적으로 허용되는 미셀-형성 계면활성제;(iii) 벌크화제; 및(iv) 안정제를 포함하는 안정화된 동결건조 조제물로서,여기에서 상기 계면활성제가 1:1.75 내지 1:25의 에키노칸딘 화합물 대 미셀-형성 계면활성제의 중량비로 상기 조제물에 존재하고, 상기 에키노칸딘 화합물이 0.1중량% 내지 60중량%의 양으로 존재하고;상기 안정제는 탄수화물이고;상기 벌크화제는 만니톨, 수크로스, 트레할로스, 락토스 및 그것들의 혼합물, 및 덱스트란, 히드록시에틸 녹말, 피콜 및 젤라틴으로 구성된 군으로부터 선택되고; 그리고상기 에키노칸딘 화합물이 다음 구조식 및 제약학적으로 허용되는 그것의 염으로 표시되는 것을 특징으로 하는 조제물.상기식에서,R은 다음 일반 구조식을 갖는 기이고;(상기식에서 A, B, C 및 D는 독립적으로 수소, C1-C12 알킬, C2-C12 알킨일, C1-C12 알콕시, C1-C12 알킬티오, 할로, 또는 -O-(CH2)m-[O-(CH2)n]p-O-(C1-C12알킬) 또는 -O-(CH2)q-X-E이고;m은 2, 3 또는 4이고;n은 2, 3 또는 4이고; p는 0 또는 1이고; q는 2, 3 또는 4이고;X는 피롤리디노, 피페리디노 또는 피페라지노이고;E는 수소, C1-C12 알킬, C3-C12 시클로알킬, 벤질 또는 C3-C12 시클로알킬메틸이다.)R1, R2, R3, R6, R7 및 R10은 독립적으로 히드록시 또는 수소이고;R4는 수소, 메틸 또는 -CH2C(O)NH2이고;R5 및 R11은 독립적으로 메틸 또는 수소이고;R8은 -OH, -OPO3H2, -OPO3HCH3, -OPO2HCH3 또는 -OSO3H이고;R9는 -H, -OH 또는 -OSO3H이다.
- 제 22 항에 있어서, 상기 벌크화제는 만니톨, 수크로스, 트레할로스, 락토스 및 그것들의 혼합물로 구성된 군으로부터 선택되는 것을 특징으로 하는 조제물.
- 삭제
- 제 22 항에 있어서, 상기 미셀-형성 계면활성제가 폴리소르베이트, 폴리옥시에틸렌 스테아레이트, 소르비탄 트리올레에이트, 및 그것들의 조합으로 구성된 군으로부터 선택되는 것을 특징으로 하는 조제물.
- 제 22 항에 있어서, 상기 계면활성제가 1:1.75 내지 1:25의 에키노칸딘 대 계면활성제의 중량비로 상기 조제물에 존재하는 것을 특징으로 하는 조제물.
- 제 29 항에 있어서, 에키노칸딘 대 계면활성제의 상기 중량비가 1:2 내지 1:3인 것을 특징으로 하는 조제물.
- 제 22 항의 안정화된 동결건조 조제물 및 수성 용매를 용액 중에 포함하는 비경구적 조제물.
- 제 31 항에 있어서, 안정제는 프럭토스, 트레할로스, 또는 그것들의 혼합물인 것을 특징으로 하는 조제물.
- 제 32 항에 있어서, 상기 안정제가 프럭토스인 것을 특징으로 하는 조제물.
- 제 31 항에 있어서, 상기 계면활성제가 1:1.75 내지 1:25의 에키노칸딘 대 계면활성제의 중량비로 상기 조제물에 존재하는 것을 특징으로 하는 조제물.
- 제 31 항에 있어서, 완충액을 더 포함하는 것을 특징으로 하는 조제물.
- 제 35 항에 있어서, 상기 완충액이 아세테이트, 타르트레이트, 시트레이트, 포스페이트 및 아미노산으로 구성된 군으로부터 선택되는 것을 특징으로 하는 조제물.
- 수성 용매중에서 에키노칸딘 화합물 또는 상기 에키노칸딘 화합물을 함유하는 에키노칸딘/탄수화물 복합체와 제약학적으로 허용되는 미셀-형성 계면활성제 및 안정제를 혼합하는 단계를 포함하는 안정화된 비경구적 조제물의 제조 방법으로서,여기에서 상기 미셀-형성 계면활성제가 1:1.75 내지 1:25의 에키노칸딘 화합물 대 계면활성제의 중량비로 상기 조제물에 존재하고, 상기 에키노칸딘 화합물이 1mg/ml와 같거나 또는 이상인 양으로 용액 중에 존재하며, 안정제는 탄수화물이고, 그리고 상기 에키노칸틴 화합물은 다음 구조식 및 제약학적으로 허용되는 그것의 염으로 표시되는 것을 특징으로 하는 안정화된 비경구적 조제물의 제조 방법.상기식에서,R은 다음 일반 구조식을 갖는 기이고;(상기식에서 A, B, C 및 D는 독립적으로 수소, C1-C12 알킬, C2-C12 알킨일, C1-C12 알콕시, C1-C12 알킬티오, 할로, 또는 -O-(CH2)m-[O-(CH2)n]p-O-(C1-C12알킬) 또는 -O-(CH2)q-X-E이고;m은 2, 3 또는 4이고;n은 2, 3 또는 4이고; p는 0 또는 1이고; q는 2, 3 또는 4이고;X는 피롤리디노, 피페리디노 또는 피페라지노이고;E는 수소, C1-C12 알킬, C3-C12 시클로알킬, 벤질 또는 C3-C12 시클로알킬메틸이다.)R1, R2, R3, R6, R7 및 R10은 독립적으로 히드록시 또는 수소이고;R4는 수소, 메틸 또는 -CH2C(O)NH2이고;R5 및 R11은 독립적으로 메틸 또는 수소이고;R8은 -OH, -OPO3H2, -OPO3HCH3, -OPO2HCH3 또는 -OSO3H이고;R9는 -H, -OH 또는 -OSO3H이다.
- 제 37 항에 있어서, 상기 에키노칸딘 화합물이 1mg/ml 내지 50mg/ml의 양으로 용액 중에 존재하는 것을 특징으로 하는 방법.
- 제 37 항에 있어서, 상기 에키노칸딘 화합물이 1mg/ml 내지 30mg/ml의 양으로 용액 중에 존재하는 것을 특징으로 하는 방법.
- 다음의 순서로(i) 제약학적으로 허용되는 미셀-형성 계면활성제, 안정제, 및 벌크화제의 존재하에 에키노칸딘 화합물 또는 상기 에키노칸딘 화합물을 함유하는 에키노칸딘/탄수화물 복합체를 수성 용매에 용해시켜 용액을 형성하는 단계[여기에서 상기 계면활성제가 용액의 부피 당 1중량% 이상의 양으로 존재하고,상기 벌크화제는 만니톨, 수크로스, 트레할로스, 락토스 및 그것들의 혼합물, 및 덱스트란, 히드록시에틸 녹말, 피콜 및 젤라틴으로 구성된 군으로부터 선택되고,상기 안정제는 탄수화물이고, 그리고상기 에키노칸딘 화합물이 다음 구조식 및 제약학적으로 허용되는 그것의 염으로 표시되며,상기식에서,R은 다음 일반 구조식을 갖는 기이고;(상기식에서 A, B, C 및 D는 독립적으로 수소, C1-C12 알킬, C2-C12 알킨일, C1-C12 알콕시, C1-C12 알킬티오, 할로, 또는 -O-(CH2)m-[O-(CH2)n]p-O-(C1-C12알킬) 또는 -O-(CH2)q-X-E이고;m은 2, 3 또는 4이고;n은 2, 3 또는 4이고; p는 0 또는 1이고; q는 2, 3 또는 4이고;X는 피롤리디노, 피페리디노 또는 피페라지노이고;E는 수소, C1-C12 알킬, C3-C12 시클로알킬, 벤질 또는 C3-C12 시클로알킬메틸이다. )R1, R2, R3, R6, R7 및 R10은 독립적으로 히드록시 또는 수소이고;R4는 수소, 메틸 또는 -CH2C(O)NH2이고;R5 및 R11은 독립적으로 메틸 또는 수소이고;R8은 -OH, -OPO3H2, -OPO3HCH3, -OPO2HCH3 또는 -OSO3H이고;R9는 -H, -OH 또는 -OSO3H이다.];(ii) 상기 용액을 멸균여과하는 단계; 및(iii) 상기 용액을 동결건조하는 단계를 포함하는 안정화된 동결건조 조제물의 제조 방법.
- 제 40 항에 있어서, 단계 (ii) 전에 하나 이상의 완충액, 등장제 또는 그것들의 조합을 첨가하는 단계를 더 포함하는 것을 특징으로 하는 방법.
- 제 40 항에 있어서, 상기 미셀-형성 계면활성제를 폴리소르베이트, 폴리옥시에틸렌 스테아레이트, 및 그것들의 조합으로 구성된 군으로부터 선택하는 것을 특징으로 하는 방법.
- (i) 4.0 내지 5.5의 pH로 비독성 수성 용매를 완충시켜 완충 용액을 형성하는 단계;(ii) 제약학적으로 허용되는 미셀-형성 계면활성제를 상기 완충 용액에 첨가하는 단계;(iii) 5℃ 내지 15℃의 온도로 단계 (ii)로부터의 용액을 냉각시켜 냉각 용액을 형성하는 단계;(iv) 상기 냉각 용액에 에키노칸딘 화합물 또는 에키노칸딘/탄수화물 복합체 및 제 2의 비독성 수성 용매를 포함하는 슬러리를 첨가하는 단계 및 상기 에키노칸딘 화합물을 포함하는 상기 슬러리를 용해하여 용액을 형성하고[여기에서 상기 에키노칸틴 화합물은 다음 구조식 및 제약학적으로 허용되는 그것의 염으로 표시되며,상기식에서,R은 다음 일반 구조식을 갖는 기이고;(상기식에서 A, B, C 및 D는 독립적으로 수소, C1-C12 알킬, C2-C12 알킨일, C1-C12 알콕시, C1-C12 알킬티오, 할로, 또는 -O-(CH2)m-[O-(CH2)n]p-O-(C1-C12알킬) 또는 -O-(CH2)q-X-E이고;m은 2, 3 또는 4이고;n은 2, 3 또는 4이고; p는 0 또는 1이고; q는 2, 3 또는 4이고;X는 피롤리디노, 피페리디노 또는 피페라지노이고;E는 수소, C1-C12 알킬, C3-C12 시클로알킬, 벤질 또는 C3-C12 시클로알킬메틸이다.)R1, R2, R3, R6, R7 및 R10은 독립적으로 히드록시 또는 수소이고;R4는 수소, 메틸 또는 -CH2C(O)NH2이고;R5 및 R11은 독립적으로 메틸 또는 수소이고;R8은 -OH, -OPO3H2, -OPO3HCH3, -OPO2HCH3 또는 -OSO3H이고;R9는 -H, -OH 또는 -OSO3H이다.],또한 탄수화물인 안정제 및 만니톨, 수크로스, 트레할로스, 락토스, 또는 그것들의 혼합물인 벌크화제를 첨가하는 단계;(v) 단계 (iv)로부터의 상기 용액을 멸균여과하는 단계; 및(vi) 단계 (v)로부터의 상기 용액을 동결건조하는 단계를 포함하는 안정화된 동결건조 조제물의 제조 방법.
- 제 43 항에 있어서, 단계 (iii)에서 상기 온도가 7℃ 내지 10℃인 것을 특징으로 하는 방법.
- 제 43 항에 있어서, 단계 (v) 전에 하나 이상의 등장제를 첨가하는 단계를 더 포함하는 것을 특징으로 하는 방법.
- 수성 용매 및 용액 중에서 제 43 항의 방법에 의해 제조된 안정화된 동결건조 조제물을 포함하는 안정화된 비경구적 조제물.
- 삭제
- 삭제
- 삭제
- 제 1 항에 있어서, 항진균 감염의 치료에 사용되는 것을 특징으로 하는 조제물.
- 제 31 항에 있어서, 항진균 감염의 치료에 사용되는 것을 특징으로 하는 조제물.
- 제 46 항에 있어서, 항진균 감염의 치료에 사용되는 것을 특징으로 하는 조제물.
- 제 1 항에 있어서, 상기 미셀-형성 계면활성제는 폴리소르베이트, 폴리옥시에틸렌 스테아레이트, 또는 그것들의 조합인 것을 특징으로 하는 조제물.
- 제 22 항에 있어서, 상기 미셀-형성 계면활성제는 폴리소르베이트, 폴리옥시에틸렌 스테아레이트, 또는 그것들의 조합인 것을 특징으로 하는 조제물.
- 제 40 항에 있어서, 상기 미셀-형성 계면활성제는 폴리소르베이트, 폴리옥시에틸렌 스테아레이트, 또는 그것들의 조합인 것을 특징으로 하는 조제물.
- 제 1 항, 제 4 항, 제 8 항 또는 제 53 항 중 어느 한 항에 있어서, 상기 안정제는 프럭토스, 트레할로스, 또는 그것들의 혼합물인 것을 특징으로 하는 조제물.
- 제 56 항에 있어서, 상기 안정제는 프럭토스인 것을 특징으로 하는 조제물.
- 제 22 항, 제 26 항, 제 28 항, 또는 제 54 항 중 어느 한 항에 있어서, 상기 안정제는 프럭토스, 트레할로스, 또는 그것들의 혼합물인 것을 특징으로 하는 조제물.
- 제 58 항에 있어서, 상기 안정제는 프럭토스인 것을 특징으로 하는 조제물.
- 제 1 항, 제 4 항, 또는 제 12 항 중 어느 한 항에 있어서, 상기 미셀-형성 계면활성제는 10-18의 HLB 값을 갖는 것을 특징으로 하는 조제물.
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KR (1) | KR100613136B1 (ko) |
CN (1) | CN100335122C (ko) |
AT (1) | ATE294571T1 (ko) |
AU (1) | AU776782C (ko) |
BR (1) | BRPI0009249B8 (ko) |
CA (1) | CA2362481C (ko) |
CY (2) | CY1114631T1 (ko) |
DE (1) | DE60019902D1 (ko) |
DK (1) | DK1582204T3 (ko) |
ES (1) | ES2433678T3 (ko) |
HK (2) | HK1040062A1 (ko) |
IL (1) | IL145185A0 (ko) |
PT (1) | PT1582204E (ko) |
RU (1) | RU2250763C2 (ko) |
WO (1) | WO2000051564A1 (ko) |
ZA (1) | ZA200108002B (ko) |
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US11318110B2 (en) | 2015-08-28 | 2022-05-03 | Caliway Biopharmaceuticals Co., Ltd. | Pharmaceutical composition for reducing local fat and uses thereof |
MX2018002462A (es) * | 2015-08-28 | 2018-06-19 | Caliway Biopharmaceuticals Co Ltd | Una composicion farmaceutica para reducir la grasa localizada y sus usos. |
WO2017037232A1 (en) * | 2015-09-02 | 2017-03-09 | Xellia Pharmaceuticals Aps | Anidulafungin formulations |
ES2955711T3 (es) | 2016-03-16 | 2023-12-05 | Cidara Therapeutics Inc | Regímenes de dosificación para el tratamiento de infecciones fúngicas |
MA49576A (fr) | 2017-07-12 | 2021-04-07 | Cidara Therapeutics Inc | Compositions et méthodes pour le traitement d'infections fongiques |
CN109574811B (zh) * | 2018-11-22 | 2021-12-24 | 中山大学 | 一种阿尼芬净侧链中间体对戊氧基三联苯甲酸的制备方法 |
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