HRP20191187T1 - Terapijske nanočestice koje sadrže terapijsko sredstvo, te postupci njihove proizvodnje i upotrebe - Google Patents
Terapijske nanočestice koje sadrže terapijsko sredstvo, te postupci njihove proizvodnje i upotrebe Download PDFInfo
- Publication number
- HRP20191187T1 HRP20191187T1 HRP20191187TT HRP20191187T HRP20191187T1 HR P20191187 T1 HRP20191187 T1 HR P20191187T1 HR P20191187T T HRP20191187T T HR P20191187TT HR P20191187 T HRP20191187 T HR P20191187T HR P20191187 T1 HRP20191187 T1 HR P20191187T1
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- Prior art keywords
- acid
- therapeutic
- poly
- cancer
- therapeutic nanoparticle
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- 239000002105 nanoparticle Substances 0.000 title claims 25
- 230000001225 therapeutic effect Effects 0.000 title claims 22
- 239000003814 drug Substances 0.000 title claims 14
- 229940124597 therapeutic agent Drugs 0.000 title claims 14
- 238000000034 method Methods 0.000 title claims 2
- 239000002253 acid Substances 0.000 claims 17
- 230000002209 hydrophobic effect Effects 0.000 claims 15
- 229920001223 polyethylene glycol Polymers 0.000 claims 8
- 239000012071 phase Substances 0.000 claims 7
- 229920000642 polymer Polymers 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 229920000359 diblock copolymer Polymers 0.000 claims 4
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 claims 4
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims 3
- DWZAEMINVBZMHQ-UHFFFAOYSA-N 1-[4-[4-(dimethylamino)piperidine-1-carbonyl]phenyl]-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea Chemical group C1CC(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C(N=C(N=2)N2CCOCC2)N2CCOCC2)C=C1 DWZAEMINVBZMHQ-UHFFFAOYSA-N 0.000 claims 3
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims 3
- 239000003613 bile acid Substances 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 claims 3
- 239000000839 emulsion Substances 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 claims 2
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 claims 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 239000004380 Cholic acid Substances 0.000 claims 2
- 239000005642 Oleic acid Substances 0.000 claims 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims 2
- 150000007513 acids Chemical class 0.000 claims 2
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 claims 2
- 229960002471 cholic acid Drugs 0.000 claims 2
- 235000019416 cholic acid Nutrition 0.000 claims 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims 2
- 229930195729 fatty acid Natural products 0.000 claims 2
- 239000000194 fatty acid Substances 0.000 claims 2
- 150000004665 fatty acids Chemical class 0.000 claims 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims 2
- 239000003446 ligand Substances 0.000 claims 2
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 claims 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims 2
- 230000008685 targeting Effects 0.000 claims 2
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 claims 2
- BITHHVVYSMSWAG-KTKRTIGZSA-N (11Z)-icos-11-enoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCC(O)=O BITHHVVYSMSWAG-KTKRTIGZSA-N 0.000 claims 1
- GWHCXVQVJPWHRF-KTKRTIGZSA-N (15Z)-tetracosenoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-KTKRTIGZSA-N 0.000 claims 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 claims 1
- UNSRRHDPHVZAHH-UHFFFAOYSA-N 6beta,11alpha-Dihydroxy-3alpha,5alpha-cyclopregnan-20-on Natural products CCCCCCCCC=CCC=CCC=CCCCC(O)=O UNSRRHDPHVZAHH-UHFFFAOYSA-N 0.000 claims 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 claims 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 claims 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims 1
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 206010023774 Large cell lung cancer Diseases 0.000 claims 1
- SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 claims 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 1
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 claims 1
- XJXROGWVRIJYMO-SJDLZYGOSA-N Nervonic acid Natural products O=C(O)[C@@H](/C=C/CCCCCCCC)CCCCCCCCCCCC XJXROGWVRIJYMO-SJDLZYGOSA-N 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 208000006265 Renal cell carcinoma Diseases 0.000 claims 1
- 206010041067 Small cell lung cancer Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 229960001091 chenodeoxycholic acid Drugs 0.000 claims 1
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 claims 1
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 claims 1
- GWHCXVQVJPWHRF-UHFFFAOYSA-N cis-tetracosenoic acid Natural products CCCCCCCCC=CCCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-UHFFFAOYSA-N 0.000 claims 1
- 229920001577 copolymer Polymers 0.000 claims 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 claims 1
- 229960003964 deoxycholic acid Drugs 0.000 claims 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 claims 1
- 229940108623 eicosenoic acid Drugs 0.000 claims 1
- BITHHVVYSMSWAG-UHFFFAOYSA-N eicosenoic acid Natural products CCCCCCCCC=CCCCCCCCCCC(O)=O BITHHVVYSMSWAG-UHFFFAOYSA-N 0.000 claims 1
- 230000001804 emulsifying effect Effects 0.000 claims 1
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- SMEROWZSTRWXGI-HVATVPOCSA-N lithocholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 SMEROWZSTRWXGI-HVATVPOCSA-N 0.000 claims 1
- 201000009546 lung large cell carcinoma Diseases 0.000 claims 1
- 201000010893 malignant breast melanoma Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 206010027191 meningioma Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 claims 1
- 235000021315 omega 9 monounsaturated fatty acids Nutrition 0.000 claims 1
- 239000012074 organic phase Substances 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 210000004214 philadelphia chromosome Anatomy 0.000 claims 1
- 238000010791 quenching Methods 0.000 claims 1
- 230000000171 quenching effect Effects 0.000 claims 1
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 claims 1
- 229960001661 ursodiol Drugs 0.000 claims 1
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- 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
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
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- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
- A61K9/5153—Polyesters, e.g. poly(lactide-co-glycolide)
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
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- General Chemical & Material Sciences (AREA)
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- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
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- Inorganic Chemistry (AREA)
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- Biophysics (AREA)
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- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
Claims (18)
1. Terapijska nanočestica, naznačena time što sadrži:
uglavnom hidrofobnu kiselinu;
terapijsko sredstvo, gdje je pKa protoniranog terapijskog sredstva u najmanju ruku otprilike 1,0 pKa jedinica veća od pKa hidrofobne kiseline; i
polimer, kojeg se bira između diblok kopolimera poli(mliječna) kiselina-poli(etilen)glikola ili diblok kopolimera poli(mliječna kiselina-ko-glikolna kiselina)-poli(etilen)glikola i njihove kombinacije;
gdje je terapijsko sredstvo 1-(4-{[4-(dimetilamino)piperidin-1-il]karbonil}fenil)-3-[4-(4,6-dimorfolin-4-il-1,3,5-triazin-2-il)fenil]urea, ili njezina farmaceutski prihvatljiva sol.
2. Terapijska nanočestica u skladu s patentnim zahtjevom 1, naznačena time što se molarni omjer između uglavnom hidrofobne kiseline i terapijskog sredstva kreće u rasponu od otprilike 0,25:1 do otprilike 2:1.
3. Terapijska nanočestica u skladu s patentnim zahtjevom 2, naznačena time što sadrži otprilike 0,2 do otprilike 25 težinskih postotaka terapijskog sredstva i otprilike 50 do otprilike 99,75 težinskih postotaka polimera, te što nanočestica sadrži otprilike 10 do otprilike 30 težinskih postotaka poli(etilen)glikola.
4. Terapijska nanočestica u skladu s patentnim zahtjevom 1, naznačena time što sadrži otprilike 0,05 do otprilike 30 težinskih postotaka uglavnom hidrofobne kiseline; otprilike 0,2 do otprilike 25 težinskih postotaka terapijskog sredstva; i otprilike 50 do otprilike 99,75 težinskih postotaka polimera; gdje terapijska nanočestica sadrži otprilike 10 do otprilike 30 težinskih postotaka poli(etilen)glikola.
5. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačena time što uglavnom hidrofobna kiselina i terapijsko sredstvo tvore hidrofobni ionski par u terapijskoj nanočestici.
6. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačena time što je hidrofobna kiselina masna kiselina, po mogućnosti gdje je masna kiselina omega-9 masna kiselina, koju se bira iz skupine koju čine: oleinska kiselina, ikozenoinska kiselina, Meadova kiselina, erucinska kiselina, nervonska kiselina, te njihove kombinacije.
7. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačena time što je hidrofobna kiselina žučna kiselina, po mogućnosti gdje se žučnu kiselinu bira iz skupine koju čine henodeoksikolna kiselina, ursodeoksikolna kiselina, deoksikolna kiselina, hikolna kiselina, β-murikolna kiselina, kolna kiselina, litokolna kiselina, žučna kiselina konjugirana s aminokiselinom, te njihove kombinacije.
8. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačena time što se hidrofobnu kiselinu bira iz skupine koju čine dioktil-sulfojantarna kiselina, 1-hidroksi-2-naftojeva kiselina, dodecilsumporna kiselina, naftalen-1,5-disulfonska kiselina, naftalen-2-sulfonska kiselina, pamoinska kiselina, undekanska kiselina, te njihove kombinacije.
9. Terapijska nanočestica u skladu s patentnim zahtjevom 8, naznačena time što je hidrofobna kiselina pamoinska kiselina.
10. Terapijska nanočestica u skladu s patentnim zahtjevom 1, naznačena time što sadrži:
pamoinsku kiselinu kao uglavnom hidrofobnu kiselinu;
1-(4-{[4-(dimetilamino)piperidin-1-il]karbonil}fenil)-3-[4-(4,6-dimorfolin-4-il-1,3,5-triazin-2-il)fenil]ureu ili njezina farmaceutski prihvatljivu sol kao terapijsko sredstvo; i
polimer, kojeg se bira između diblok kopolimera poli(mliječna) kiselina-poli(etilen)glikola ili diblok kopolimera poli(mliječna kiselina-ko-glikolna kiselina)-poli(etilen)glikola i njihove kombinacije;
gdje se molarni omjer između pamoinske kiseline i terapijskog sredstva kreće u rasponu od otprilike 0,25:1 do otprilike 2:1.
11. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačena time što dodatno sadrži otprilike 0,2 do otprilike 30 težinskih postotaka poli(mliječna) kiselina-poli(etilen)glikola ili kopolimera poli(mliječna) kiselina-ko-poli(glikolna) kiselina-poli(etilen)glikol, funkcionaliziranog ciljajućim ligandom.
12. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačena time što je uglavnom hidrofobna kiselina smjesa dvije uglavnom hidrofobne kiseline, po mogućnosti gdje su dvije uglavnom hidrofobne kiseline oleinska kiselina i kolna kiselina.
13. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 12, naznačena time što dodatno sadrži ciljajući ligand, koji je PLA-PEG-GL, gdje GL ima sljedeću strukturu:
.
14. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 13, naznačena time što nanočestice sadrže otprilike 1 do otprilike 20 težinskih postotaka terapijskog sredstva, primjerice otprilike 1, otprilike 2, otprilike 3, otprilike 4, otprilike 5, otprilike 6, otprilike 7, otprilike 8, otprilike 9, otprilike 10, otprilike 11, otprilike 12, otprilike 13, otprilike 14, otprilike 15, otprilike 16, otprilike 17, otprilike 18, otprilike 19 ili otprilike 20 težinskih postotaka terapijskog sredstva.
15. Farmaceutski pripravak, naznačen time što sadrži terapijsku nanočesticu u skladu s bilo kojim od patentnih zahtjeva 1 do 14, kao i farmaceutski prihvatljivu pomoćnu tvar.
16. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 14 ili farmaceutski pripravak u skladu s patentnim zahtjevom 15, naznačeni time što su namijenjeni upotrebi u liječenju raka, gdje se po mogućnosti rak bira iz skupine koju čine kronična mijelogena leukemija, kronična mijelomonocitna leukemija, hipereozinofilni sindrom, karcinom bubrežnih stanica, hepatocelularni karcinom, akutna limfoblastična leukemija pozitivna na filadelfijski kromosom, rak velikih stanica pluća, rak gušterače, rak dojke, čvrsti tumor, tumor gastrointestinalne strome, rak glave i vrata i limfom stanica plašta.
17. Terapijska nanočestica u skladu s bilo kojim od patentnih zahtjeva 1 do 14 ili farmaceutski pripravak u skladu s patentnim zahtjevom 15, naznačeni time što su namijenjeni upotrebi u liječenju karcinoma endometrija, glioblastoma, raka prostate, raka bubrega, karcinoma malih stanica pluća, meningioma, raka glave i vrata, raka štitnjače, raka mokraćnog mjehura, kolorektalnog raka, raka dojke ili melanoma.
18. Postupak priprave terapijske nanočestice u skladu s bilo kojim od patentnih zahtjeva 1 do 14, naznačen time što se sastoji u koracima:
kombiniranja prve organske faze s prvom vodenom otopinom kako bi se dobilo drugu fazu;
emulgiranja druge faze kako bi se dobilo emulzijsku fazu, gdje emulzijska faza sadrži prvi polimer, terapijsko sredstvo i uglavnom hidrofobnu kiselinu;
gašenja emulzijske faza, čime se dobije gašenu fazu; i
filtriranja ugašene faze kako bi se dobilo terapijske nanočestice, gdje je terapijsko sredstvo 1-(4-{[4-(dimetilamino)piperidin-1-il]karbonil}fenil)-3-[4-(4,6-dimorfolin-4-il-1,3,5-triazin-2-il)fenil]urea, ili njezina farmaceutski prihvatljiva sol.
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