CN109310622A - 尼古丁颗粒和组合物 - Google Patents
尼古丁颗粒和组合物 Download PDFInfo
- Publication number
- CN109310622A CN109310622A CN201780034796.4A CN201780034796A CN109310622A CN 109310622 A CN109310622 A CN 109310622A CN 201780034796 A CN201780034796 A CN 201780034796A CN 109310622 A CN109310622 A CN 109310622A
- Authority
- CN
- China
- Prior art keywords
- nicotine
- particle
- weight
- sugar
- amino acid
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 239000002245 particle Substances 0.000 title claims abstract description 131
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 title claims abstract description 102
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 title claims abstract description 88
- 229960002715 nicotine Drugs 0.000 title claims abstract description 88
- 239000000203 mixture Substances 0.000 title claims abstract description 74
- 150000001413 amino acids Chemical class 0.000 claims abstract description 42
- 235000000346 sugar Nutrition 0.000 claims abstract description 34
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 11
- 235000001014 amino acid Nutrition 0.000 claims description 40
- 229940024606 amino acid Drugs 0.000 claims description 40
- 239000007788 liquid Substances 0.000 claims description 28
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 24
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 21
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 11
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 7
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 7
- BWLBGMIXKSTLSX-UHFFFAOYSA-N 2-hydroxyisobutyric acid Chemical compound CC(C)(O)C(O)=O BWLBGMIXKSTLSX-UHFFFAOYSA-N 0.000 claims description 6
- SDVKWBNZJFWIMO-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;3-(1-methylpyrrolidin-2-yl)pyridine Chemical compound CN1CCCC1C1=CC=CN=C1.OC(=O)CC(O)(C(O)=O)CC(O)=O SDVKWBNZJFWIMO-UHFFFAOYSA-N 0.000 claims description 6
- VWTHFJXLFGINSW-PPHPATTJSA-N 2-hydroxypropanoic acid;3-[(2s)-1-methylpyrrolidin-2-yl]pyridine Chemical compound CC(O)C(O)=O.CN1CCC[C@H]1C1=CC=CN=C1 VWTHFJXLFGINSW-PPHPATTJSA-N 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- 229940009098 aspartate Drugs 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 3
- 235000004279 alanine Nutrition 0.000 claims description 3
- 230000000954 anitussive effect Effects 0.000 claims description 3
- 229940124584 antitussives Drugs 0.000 claims description 3
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 229930182817 methionine Natural products 0.000 claims description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 3
- 239000004474 valine Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose 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](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 241000195493 Cryptophyta Species 0.000 claims description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose 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)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 2
- 229960000310 isoleucine Drugs 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 claims 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims 1
- 239000002131 composite material Substances 0.000 claims 1
- 239000002253 acid Substances 0.000 description 26
- 235000005772 leucine Nutrition 0.000 description 18
- 238000004220 aggregation Methods 0.000 description 9
- 230000002776 aggregation Effects 0.000 description 9
- 238000009826 distribution Methods 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- 238000001694 spray drying Methods 0.000 description 6
- 239000003513 alkali Substances 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000004310 lactic acid Substances 0.000 description 4
- 235000014655 lactic acid Nutrition 0.000 description 4
- 125000000647 trehalose group Chemical group 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229940107700 pyruvic acid Drugs 0.000 description 3
- 230000000391 smoking effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical group [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 2
- BLUGYPPOFIHFJS-UUFHNPECSA-N (2s)-n-[(2s)-1-[[(3r,4s,5s)-3-methoxy-1-[(2s)-2-[(1r,2r)-1-methoxy-2-methyl-3-oxo-3-[[(1s)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 BLUGYPPOFIHFJS-UUFHNPECSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- 208000007934 ACTH-independent macronodular adrenal hyperplasia Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 150000002614 leucines Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- GKTOAHZEMRRUKF-HVDRVSQOSA-N (2s)-2-aminopentanedioic acid;3-(1-methylpyrrolidin-2-yl)pyridine Chemical compound OC(=O)[C@@H](N)CCC(O)=O.CN1CCCC1C1=CC=CN=C1 GKTOAHZEMRRUKF-HVDRVSQOSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- SKZDZXPBBYUFBY-WLHGVMLRSA-N (e)-but-2-enedioic acid;3-(1-methylpyrrolidin-2-yl)pyridine Chemical compound OC(=O)\C=C\C(O)=O.CN1CCCC1C1=CC=CN=C1 SKZDZXPBBYUFBY-WLHGVMLRSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
- AIBWPBUAKCMKNS-PPHPATTJSA-N 2-hydroxybenzoic acid;3-[(2s)-1-methylpyrrolidin-2-yl]pyridine Chemical compound OC(=O)C1=CC=CC=C1O.CN1CCC[C@H]1C1=CC=CN=C1 AIBWPBUAKCMKNS-PPHPATTJSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- HDJBTCAJIMNXEW-PPHPATTJSA-N 3-[(2s)-1-methylpyrrolidin-2-yl]pyridine;hydrochloride Chemical compound Cl.CN1CCC[C@H]1C1=CC=CN=C1 HDJBTCAJIMNXEW-PPHPATTJSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 1
- REJHVSOVQBJEBF-OWOJBTEDSA-N 5-azaniumyl-2-[(e)-2-(4-azaniumyl-2-sulfonatophenyl)ethenyl]benzenesulfonate Chemical compound OS(=O)(=O)C1=CC(N)=CC=C1\C=C\C1=CC=C(N)C=C1S(O)(=O)=O REJHVSOVQBJEBF-OWOJBTEDSA-N 0.000 description 1
- AQHLWAARHKACOY-UHFFFAOYSA-N Amsonic acid Natural products N1C2=CC=CC=C2C2=C1C1CC3C(C(O)=O)COC(C)(O)C3CN1CC2 AQHLWAARHKACOY-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 229930182843 D-Lactic acid Natural products 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000001293 FEMA 3089 Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- UJNOLBSYLSYIBM-WISYIIOYSA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (2r)-2-hydroxypropanoate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)[C@@H](C)O UJNOLBSYLSYIBM-WISYIIOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- WWIWLTSSHDKOKO-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1.OS(=O)(=O)C1=CC=CC=C1 WWIWLTSSHDKOKO-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229930006722 beta-pinene Natural products 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- UTEFBSAVJNEPTR-RGEXLXHISA-N loprazolam Chemical compound C1CN(C)CCN1\C=C/1C(=O)N2C3=CC=C([N+]([O-])=O)C=C3C(C=3C(=CC=CC=3)Cl)=NCC2=N\1 UTEFBSAVJNEPTR-RGEXLXHISA-N 0.000 description 1
- 229960003019 loprazolam Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- SJOXEWUZWQYCGL-DVOMOZLQSA-N menthyl salicylate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)C1=CC=CC=C1O SJOXEWUZWQYCGL-DVOMOZLQSA-N 0.000 description 1
- 229960004665 menthyl salicylate Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229940069688 nicotine bitartrate Drugs 0.000 description 1
- LDMPZNTVIGIREC-ZGPNLCEMSA-N nicotine bitartrate Chemical compound O.O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.CN1CCC[C@H]1C1=CC=CN=C1 LDMPZNTVIGIREC-ZGPNLCEMSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 108010026901 peptide 106 Proteins 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 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
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- SJOXEWUZWQYCGL-UHFFFAOYSA-N salicylic acid menthyl ester Natural products CC(C)C1CCC(C)CC1OC(=O)C1=CC=CC=C1O SJOXEWUZWQYCGL-UHFFFAOYSA-N 0.000 description 1
- 235000021309 simple sugar Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- PNGLEYLFMHGIQO-UHFFFAOYSA-M sodium;3-(n-ethyl-3-methoxyanilino)-2-hydroxypropane-1-sulfonate;dihydrate Chemical compound O.O.[Na+].[O-]S(=O)(=O)CC(O)CN(CC)C1=CC=CC(OC)=C1 PNGLEYLFMHGIQO-UHFFFAOYSA-M 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 238000010977 unit operation Methods 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- WTARULDDTDQWMU-UHFFFAOYSA-N β-pinene Chemical compound C1C2C(C)(C)C1CCC2=C WTARULDDTDQWMU-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/465—Nicotine; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1658—Proteins, e.g. albumin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Addiction (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Management, Administration, Business Operations System, And Electronic Commerce (AREA)
- Financial Or Insurance-Related Operations Such As Payment And Settlement (AREA)
Abstract
组合物由多个颗粒形成。这些颗粒包括尼古丁、糖和氨基酸或短肽。
Description
技术领域
本公开涉及适合吸入的尼古丁颗粒和组合物。这些尼古丁颗粒和组合物包括尼古丁、糖和氨基酸。
背景技术
干粉吸入器(DPI)是已知的并且被用于治疗呼吸道疾病，其通过将包含药物活性化合物的干燥粉末以气溶胶形式经由吸入而递送至患者的呼吸道。在药物干燥粉末中，活性药物成分(API)通常聚集在如乳糖之类较大载体颗粒的表面上。DPI操作复杂的机构以确保这类聚结物在API被吸入肺中之前分散、分解或解聚。
在吸入时以在常规吸烟方式吸入或气流速率内的气流速率将尼古丁颗粒递送至肺中可能比较困难。尼古丁颗粒可能会聚集并粘在吸入器或加工表面上，尤其是在尼古丁颗粒的尺寸减小时。MMAD小于约10微米的尼古丁颗粒由于表面积对体积比较高，使得表面自由能随这种减小的颗粒尺寸而增加，并由此增加颗粒聚集的倾向以及聚集体的强度，往往会具有增大的热力学不稳定性。形成尼古丁颗粒可能是困难且昂贵的。
希望提供可以容易地形成和加工的尼古丁颗粒和组合物。希望的是，尼古丁颗粒和组合物不会粘于加工表面或聚集体上，并且展现出稳定的粒度分布。还希望能够以在常规吸烟方式吸入或气流速率内的气流速率将这些尼古丁颗粒和组合物递送至肺。
发明内容
本公开涉及一种包含尼古丁、糖和氨基酸的颗粒。所述颗粒的尺寸优选地在约0.5至约10微米范围内，或在约0.5至约5微米范围内。所述颗粒优选地包含约25重量％或更少的尼古丁或约5至约15重量％的尼古丁。自由流动组合物可以由这些颗粒形成。
所述颗粒可以通过将尼古丁、糖和氨基酸组合于液体载体中形成液体混合物来形成。对该液体混合物进行喷雾干燥以形成尺寸在约0.5至约10微米范围内或在约0.5至约5微米范围内的多个颗粒。所述多个颗粒优选地是均匀颗粒。
有利的是，本文所述的尼古丁颗粒和粉末配制物提供足以在常规吸烟制剂吸入或气流速率范围内的吸入或气流速率将尼古丁递送至消费者肺部的均匀且稳定的粒度。本文所述的尼古丁颗粒和粉末配制物允许通过喷雾干燥达到特定且受控制的粒度分布来形成这些颗粒，同时最大限度地减少聚集或粘附于如加工设备表面等表面。喷雾干燥可提供可缩放、精确且低成本的颗粒形成单元操作。
术语“尼古丁”是指任何形式的尼古丁和尼古丁衍生物，包括但不限于游离碱尼古丁、尼古丁盐，或者在基质如糖基质或有机金属络合物中。
术语“氨基酸”是指单个未修饰或修饰过的氨基酸部分，优选地是未修饰的。
术语“短肽”是指包含两个或三个氨基酸的肽。
如本文所述，颗粒的尺寸优选地是指颗粒的气动直径。粉末系统的空气动力学直径优选地用阶式撞击取样器(cascade impactor)测量。术语“MMAD”是指质量中值气动直径。
本公开涉及包含尼古丁、糖和氨基酸的颗粒。形成的颗粒可具有特定粒度分布。在示例性实例中，约90％，或约95％，或约98％的颗粒的尺寸是约5微米或更小，或约4.5微米或更小，或约4.2微米或更小，并且约50％的颗粒的尺寸是约2.5微米或更小，或约2.1微米或更小。在许多此类实例中，约10％的颗粒具有约820纳米或更小的尺寸。这些颗粒可具有在约1至约4微米范围内的质量中值气动直径。基本上所有颗粒都可以具有在约500纳米至约5微米范围内的粒度。
这些颗粒的组合物具有特定粒度分布。在示例性实例中，所述组合物中约90％，或约95％，或约98％的颗粒的尺寸是约5微米或更小，或约4.5微米或更小，或约4.2微米或更小，并且约50％的颗粒的尺寸是约2.5微米或更小，或约2.1微米或更小。在许多此类实例中，约10％的颗粒具有约820纳米或更小的尺寸。所述组合物中的颗粒可具有在约1至约4微米范围内的质量中值气动直径。基本上所有的形成组合物的颗粒可以具有在约500纳米至约5微米范围内的粒度。与本文所述的粒度分布相关的百分比是基于以体积计的颗粒(体积％)。
所述颗粒的尼古丁组分可以是游离碱尼古丁、尼古丁盐或其组合。尼古丁组分可以是通过将尼古丁或尼古丁游离碱与酸组合而形成的尼古丁盐。所述酸可以是相对于尼古丁游离碱化学计量的量的酸，或可以将化学计量过量的酸与尼古丁游离碱组合，或者可以将化学计量过量的尼古丁游离碱与酸组合。可利用游离碱尼古丁，而不添加酸。
所述酸可以是有机酸、无机酸或路易斯酸。无机酸的非限制性实例是盐酸、氢溴酸、氢碘酸、硝酸、硫酸、磷酸、乙酸、六氟磷酸等等。有机酸的非限制性实例是乙酰丙酸、柠檬酸、葡萄糖酸、苯甲酸、丙酸、丁酸、磺基水杨酸、顺丁烯二酸、月桂酸、苹果酸、反丁烯二酸、琥珀酸、酒石酸、氨芪磺酸(amsonic)、扑酸(pamoic)、甲磺酸、天冬氨酸、甲酸、乙酸、丙酸、琥珀酸、樟脑磺酸、反丁烯二酸、羟基乙磺酸、乳酸、粘酸、对甲苯磺酸、乙醇酸、葡萄糖醛酸、顺丁烯二酸、糠酸、谷氨酸、苯甲酸、邻氨基苯甲酸、水杨酸、苯乙酸、丙酮酸、扁桃酸、恩波酸(embonic)(扑酸)、甲烷磺酸、乙烷磺酸、泛酸、苯磺酸(苯磺酸酯)、硬脂酸、磺胺酸、藻酸、半乳糖醛酸等等。路易斯酸的非限制性实例是氯化锌或溴化锌(ZnCl2/ZnBr2)。这些酸可与尼古丁反应形成有机金属络合物。
有用的尼古丁盐包括但不限于例如尼古丁丙酮酸盐、尼古丁柠檬酸盐、尼古丁天冬氨酸盐、尼古丁乳酸盐、尼古丁酒石酸氢盐、尼古丁水杨酸盐、尼古丁反丁烯二酸盐、尼古丁单丙酮酸盐、尼古丁谷氨酸盐或尼古丁盐酸盐。优选的尼古丁盐包括尼古丁乳酸盐、尼古丁丙酮酸盐、尼古丁柠檬酸盐、尼古丁天冬氨酸盐或其组合。
所述颗粒(溶于水中)的pH值可以在约5至约9范围内。优选地，pH值是约7.0或更高，或在7.0至9.0范围内。不含有机酸的颗粒可达到pH 9，而当形成尼古丁盐时，可使用强酸或二酸达到pH 5.0。
所述颗粒可包括氨基酸或肽(优选地由三个或更少氨基酸形成)。氨基酸或肽可降低形成组合物的颗粒的粘附力，并减少或防止形成组合物的颗粒聚集。因此，本文所述的形成组合物的颗粒可以是自由流动材料，并且在加工、运输和存储期间具有稳定的相对粒度分布。氨基酸可以是单个氨基酸或含有两个或更多个氨基酸的分子，如肽。
可用的氨基酸可包括亮氨酸、丙氨酸、缬氨酸、异亮氨酸、蛋氨酸、苯丙氨酸、酪氨酸、色氨酸或其组合。一个优选的氨基酸是亮氨酸或亮氨酸异构体，如L-亮氨酸。可用肽包括例如三亮氨酸。
所述颗粒可以包括糖。糖是指简单糖、单糖、二糖和多糖。合适糖的实例是但不限于乳糖、蔗糖、棉子糖、海藻糖、果糖、右旋糖、葡萄糖、麦芽糖、甘露醇或其组合。优选的糖包括海藻糖或甘露醇。
所述颗粒可含有低于约30重量％的尼古丁。所述颗粒可含有约25重量％或更少的尼古丁，或约15至约25重量％的尼古丁。所述颗粒可包含约1至约20重量％的尼古丁，或约10至约20重量％的尼古丁，或约5至15重量％的尼古丁。所述颗粒可含有约1至约10重量％的尼古丁，或约5至约10重量％的尼古丁。在一些实施例中，当通过喷雾干燥器加工时，包含约30重量％或更多尼古丁的颗粒聚集或粘附于加工表面上。
形成组合物的颗粒可含有低于约30重量％的尼古丁。形成组合物的颗粒可含有约25重量％或更少的尼古丁，或约15至约25重量％的尼古丁。形成组合物的颗粒可含有约1至约20重量％的尼古丁，或约10至约20重量％的尼古丁，或约5至15重量％的尼古丁。形成组合物的颗粒可含有约1至约10重量％的尼古丁或约5至约10重量％的尼古丁。在一些实施例中，含有约30重量％或更多尼古丁的形成组合物的颗粒在通过喷雾干燥器加工时产生聚集的或粘性组合物。
所述颗粒可含有约1至约10重量％的氨基酸。所述颗粒可含有约3至约7重量％的氨基酸。所述颗粒可含有约5重量％的氨基酸。将氨基酸，特别是例如L-亮氨酸添加至所述颗粒可减少聚集或粘附于加工表面。
形成组合物的颗粒可含有约1至约10重量％的氨基酸。形成组合物的颗粒可含有约3至约7重量％的氨基酸。形成组合物的颗粒可含有约5重量％的氨基酸。将氨基酸，特别是例如L-亮氨酸添加至形成组合物的颗粒在通过喷雾干燥器加工时可以减少所述组合物的聚集或粘结。
所述颗粒可含有约60至约95重量％的糖。所述颗粒可含有约70至约90重量％的糖。所述颗粒可含有约80至约85重量％的糖。
形成组合物的颗粒可含有约60至约95重量％的糖。形成组合物的颗粒可含有约70至约90重量％的糖。形成组合物的颗粒可含有约80至约85重量％的糖。
有用的颗粒配制物包括的氨基酸是亮氨酸，糖是海藻糖，并且尼古丁盐是尼古丁乳酸盐。尼古丁含量可以是约5至约15重量％或约9.5重量％。亮氨酸含量可以是约1至约10重量％亮氨酸含量可以是约3至约7重量％或约5重量％。酸:尼古丁的摩尔比可以是约1:1。
有用的颗粒配制物包括的氨基酸是亮氨酸，糖是海藻糖，并且尼古丁盐是尼古丁柠檬酸盐。尼古丁含量可以是约5至约15重量％或约9.6重量％。亮氨酸含量可以是约1至约10重量％亮氨酸含量可以是约3至约7重量％或约5重量％。酸:尼古丁的摩尔比可以是约0.25:1。
有用的颗粒配制物包括的氨基酸是亮氨酸，糖是海藻糖，并且尼古丁盐是尼古丁丙酮酸盐。尼古丁含量可以是约5至约15重量％或约9.8重量％。亮氨酸含量可以是约1至约10重量％亮氨酸含量可以是约3至约7重量％或约5重量％。酸:尼古丁的摩尔比可以是约0.6:1。
有用的颗粒配制物包括的氨基酸是亮氨酸，糖是海藻糖，并且尼古丁盐是尼古丁天冬氨酸盐。尼古丁含量可以是约5至约15重量％或约9.3重量％。亮氨酸含量可以是约1至约10重量％亮氨酸含量可以是约3至约7重量％或约5重量％。酸:尼古丁的摩尔比可以是约0.6:1。
所述颗粒可通过以下方式形成：(1)将尼古丁、糖和氨基酸或肽组合于液体载体中以形成液体混合物；和(2)对所述液体混合物进行喷雾干燥，以形成尺寸在约0.5至约10微米范围内或在约0.5至约5微米范围内的颗粒。
示例性实例包括含20％尼古丁游离碱和酸(例如乳酸、丙酮或柠檬酸)组合于液体载体中的制剂。摩尔比对于尼古丁:天冬氨酸、丙酮酸或乳酸可以在范围1.00:1.20内，并且对于尼古丁:柠檬酸在范围0.33:0.50内。液体混合物可在约30℃下温育例如约1至约15分钟，以允许形成稳定的尼古丁盐溶液。可添加药学上可接受的糖(例如海藻糖或甘露醇)和亮氨酸以形成液体混合物。所述液体混合物可通过以下方式进行喷雾干燥：使用喷嘴使液体雾化以形成液滴，使液滴与温热空气接触以干燥并形成干燥颗粒，并收集这些颗粒。在此实施例中，在喷雾干燥后，10％的颗粒(按体积计)的尺寸可以小于约0.82微米，50％的颗粒的尺寸可以小于约2.1微米，且90％的颗粒的尺寸可以小于约4.1微米。所述颗粒基本上在0.5至4.2微米范围内。
液体载体可以是例如水。液体混合物是可流动的。液体混合物被配置成流动穿过雾化或雾化器喷嘴以形成精确或受控制的粒度分布。所述颗粒或组合物可通过喷雾干燥进行加工，以形成颗粒的精确尺寸分布。本文所述的颗粒和组合物往往不会聚集或粘到喷雾干燥设备的表面。
本文所述的颗粒和组合物可以在较低温度(与常规尼古丁颗粒形成相比)下加工，使产品损失降低。例如，本文所述的颗粒和组合物可以在约50至85摄氏度范围内的温度下进行喷雾干燥。
止咳剂可以与所述组合物组合。止咳剂包括例如薄荷醇、樟脑、松节油(例如α-蒎烯、β-蒎烯)和薄荷醇衍生物(例如乳酸薄荷酯和水杨酸薄荷酯)。
然后，本文所述的颗粒和组合物可以被包装用于消费。本文所述的颗粒和组合物可被包装在吸入递送可消耗元件中，或包含在吸入递送可消耗元件内。吸入递送可消耗元件可以是例如胶囊。胶囊可以安置在吸入装置中，如干粉吸入器。吸入装置可以刺穿胶囊并且精细颗粒可被夹带在吸入空气中以递送至消费者的肺部。
本文所述的颗粒和组合物以及所述吸入递送可消耗元件可以不含或基本上不含载体颗粒。本文所述的颗粒和组合物以及所述吸入递送可消耗元件可以不含或基本上不含大于约20微米、或大于约50微米、或大于约100微米的颗粒。
尼古丁可溶解在液体载体中以形成液体混合物。糖可溶解在液体载体中以形成液体混合物。氨基酸可溶解在液体载体中以形成液体混合物。液体混合物可具有约20％w/v或更少的总固体，或约15％w/v或更少的总固体，或在约5至15％w/v范围内的总固体。
本文所述的尼古丁颗粒可以在较低(与常规尼古丁颗粒相比)温度下加工，由此可以降低产品损失。可降低喷雾干燥入口温度和出口温度。喷雾干燥雾化压力可在约3至约7巴范围内，或在4至约6巴范围内，或为约5巴。
喷雾干燥入口温度可以是约140摄氏度或更低，或约135摄氏度或更低，或约130摄氏度或更低，或在约100至1500摄氏度范围内，或在约110至约140摄氏度范围内，或在约125至约135摄氏度范围内。喷雾干燥出口温度可以是约100摄氏度或更低，或约95摄氏度或更低，或约90摄氏度或更低，、约85摄氏度或更低，或约80摄氏度或更低，或在约30至约90摄氏度范围内，或在约40至约90摄氏度范围内，或在约50至约85摄氏度范围内。
具体实例如下表所示。
除非另外说明，否则本文中使用的所有科学和技术术语均具有本领域中常用的含义。本文中所提供的定义旨在便利理解本文中频繁使用的某些术语。
除非上下文另外明确指示，否则如本文中所使用，单数形式“一个(种)”和“所述”涵盖具有复数个(种)指代物的实施例。
除非上下文另外明确指示，否则如本文中所使用，“或”一般以其包括“和/或”的意义使用。术语“和/或”意思指所列要素中的一个或全部，或者所列要素中任何两个或更多个的组合。
如本文中所使用，“具有”、“包括”、“包含”等等是以其开放式意义使用，且一般意味着“包括但不限于”。应理解，“主要由……组成”、“由……组成”等等归入“包括”等等中。
词语“优选的”和“优选地”是指在某些情况下可提供某些益处的本发明的实施例。然而，其它实施例在相同或其它情况下也可以是优选的。此外，一个或多个优选实施例的叙述并不暗示其它实施例不可用，并且不打算从包括权利要求的本公开的范围内排除其它实施例。
附图说明
图1是用于形成颗粒125的示例性方法100的示意性流程图。方法100包括在方框110，将尼古丁102、糖104和氨基酸或肽106组合于液体载体中形成液体混合物115。然后，在方框120，对液体混合物115进行喷雾干燥以形成多个颗粒125。
具体实施方式
实例
所有实例(除表3实例外)都是通过将尼古丁游离碱和酸组合于水(以指定比率组合)中形成稳定的尼古丁盐溶液来配制。然后，将糖和氨基酸(亮氨酸)与尼古丁盐溶液组合以形成液体混合物。然后，使液体混合物雾化并干燥以形成干燥颗粒，收集这些干燥颗粒以形成组合物。
表3实例通过将尼古丁游离碱与糖和氨基酸(亮氨酸)组合以形成液体混合物来配制。然后，使液体混合物雾化并干燥以形成干燥颗粒，收集这些干燥颗粒以形成组合物。
喷雾干燥器是Buchi B-290喷雾干燥器(可从美国特拉华州(DE,USA)的BuchiCorp获得)。在5巴雾化压力下，将液体混合物以2ml/min的流动速率提供至喷雾干燥器。对于利用海藻糖的实例，出口温度是约80摄氏度。下表1描述乳酸配方。下表2描述丙酮酸配方。下表3描述无酸配方。表4和表5报告各种实例的粒度分布。
表1-乳酸尼古丁粉末配方
表2-丙酮酸尼古丁粉末配方
表3-无酸(游离碱)尼古丁粉末配方
表4–粒度分布–以微米报告
X10指以体积计10％的颗粒小于此尺寸的颗粒尺寸。
X50指以体积计50％的颗粒小于此尺寸的颗粒尺寸。
X90指以体积计90％的颗粒小于此尺寸的颗粒尺寸。
VMD指体积平均直径。
表5–其它配方
Claims (15)
1.一种颗粒，其包含：
尼古丁；
糖；和
氨基酸或短肽。
2.根据权利要求1所述的颗粒，其中所述颗粒的尺寸在约0.5至约10微米范围内或在约0.5至约5微米范围内。
3.根据权利要求1或2所述的颗粒，其中所述氨基酸包含亮氨酸、丙氨酸、缬氨酸、异亮氨酸、蛋氨酸、苯丙氨酸、酪氨酸或色氨酸。
4.根据前述权利要求中任一项所述的颗粒，其中所述糖包含海藻糖或甘露醇。
5.根据前述权利要求中任一项所述的颗粒，其中所述尼古丁包含选自由以下组成的组的尼古丁盐：尼古丁乳酸盐、尼古丁丙酮酸盐、尼古丁柠檬酸盐和尼古丁天冬氨酸盐。
6.根据前述权利要求中任一项所述的颗粒，其中所述氨基酸包含亮氨酸并且所述糖包含海藻糖且所述尼古丁包含尼古丁乳酸盐。
7.根据权利要求1至5中任一项所述的颗粒，其中所述尼古丁包含尼古丁柠檬酸盐或尼古丁天冬氨酸盐。
8.根据前述权利要求中任一项所述的颗粒，其中所述颗粒包含约25重量％或更少的尼古丁或约5至约15重量％的尼古丁。
9.根据前述权利要求中任一项所述的颗粒，其中所述颗粒包含约60重量％至约95重量％的糖或约70至约90重量％的糖。
10.根据前述权利要求中任一项所述的颗粒，其中所述颗粒包含约1重量％至约10重量％的氨基酸或约3至约7重量％的氨基酸。
11.一种组合物，其包含多个根据前述权利要求中任一项所述的颗粒，其中所述多个颗粒中约90％具有约4.5微米或更小的粒度，并且所述多个颗粒中约50％具有小于约2.5微米的粒度。
12.一种方法，其包含：
将尼古丁、糖和氨基酸或短肽组合于液体载体中以形成液体混合物；以及
对所述液体混合物进行喷雾干燥以形成尺寸在约0.5至约10微米范围内或在约0.5至约5微米范围内的多个颗粒。
13.根据权利要求12所述的方法，其中所述组合步骤包含将止咳剂与在所述液体载体中的所述尼古丁、糖和氨基酸或肽组合以形成所述液体混合物。
14.根据权利要求11或12所述的方法，其中所述尼古丁是选自由尼古丁乳酸盐、尼古丁丙酮酸盐、尼古丁柠檬酸盐和尼古丁天冬氨酸盐组成的组的尼古丁盐，并且所述糖包含海藻糖、甘露醇、蔗糖或乳糖，且所述氨基酸包含亮氨酸、丙氨酸、缬氨酸、异亮氨酸、蛋氨酸、苯丙氨酸、酪氨酸或色氨酸。
15.根据权利要求12至14中任一项所述的方法，其中所述糖包含海藻糖，并且所述氨基酸包含亮氨酸，且干粉组合物包含约25重量％或更少的尼古丁或约5至约15重量％的尼古丁。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16177163.9 | 2016-06-30 | ||
| EP16177163 | 2016-06-30 | ||
| PCT/IB2017/053543 WO2018002756A1 (en) | 2016-06-30 | 2017-06-14 | Nicotine particles and compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109310622A true CN109310622A (zh) | 2019-02-05 |
Family
ID=56296661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780034796.4A Pending CN109310622A (zh) | 2016-06-30 | 2017-06-14 | 尼古丁颗粒和组合物 |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US20190133940A1 (zh) |
| EP (1) | EP3478264A1 (zh) |
| JP (2) | JP2019524648A (zh) |
| KR (1) | KR102523677B1 (zh) |
| CN (1) | CN109310622A (zh) |
| AR (1) | AR108920A1 (zh) |
| AU (1) | AU2017286864A1 (zh) |
| BR (1) | BR112018076215A2 (zh) |
| CA (1) | CA3023630A1 (zh) |
| IL (1) | IL263355A (zh) |
| MX (1) | MX2018015118A (zh) |
| PH (1) | PH12018502714A1 (zh) |
| RU (2) | RU2021132299A (zh) |
| SG (1) | SG11201809594WA (zh) |
| TW (1) | TW201801716A (zh) |
| UA (1) | UA124535C2 (zh) |
| WO (1) | WO2018002756A1 (zh) |
| ZA (1) | ZA201806949B (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114828825A (zh) * | 2019-08-30 | 2022-07-29 | 塔克索公司 | 装载的颗粒、其生产方法及其用途 |
| CN115135175A (zh) * | 2019-12-19 | 2022-09-30 | 尤尔实验室有限公司 | 有机基尼古丁凝胶组合物 |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3023630A1 (en) * | 2016-06-30 | 2018-01-04 | Philip Morris Products S.A. | Nicotine particles and compositions |
| CN112789033A (zh) * | 2018-10-02 | 2021-05-11 | 学校法人名城大学 | 吸入粉末剂、其评价方法及其用途 |
| CN110384700A (zh) * | 2019-09-03 | 2019-10-29 | 云南喜科科技有限公司 | 一种合成尼古丁的组合物 |
| BR112022008930A2 (pt) | 2019-11-14 | 2022-08-02 | Philip Morris Products Sa | Formulação em pó seco aromatizada com tabaco melhorada |
| JPWO2021201258A1 (zh) * | 2020-04-01 | 2021-10-07 | ||
| MX2023002466A (es) * | 2020-09-03 | 2023-05-19 | Philip Morris Products Sa | Composiciones en polvo activas de baja higroscopicidad. |
| US20230346696A1 (en) * | 2020-09-03 | 2023-11-02 | Philip Morris Products S.A. | Spray dried low hygroscopicity active powder compositions |
| JP2023540191A (ja) * | 2020-09-03 | 2023-09-22 | フィリップ・モーリス・プロダクツ・ソシエテ・アノニム | 凍結乾燥低吸湿性活性粉末組成物 |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001013893A2 (en) * | 1999-08-25 | 2001-03-01 | Advanced Inhalation Research, Inc. | Use of simple amino acids to form porous particles |
| CN1384733A (zh) * | 1999-10-29 | 2002-12-11 | 吸入治疗系统公司 | 分散性得到改进的干粉组合物 |
| JP2003519175A (ja) * | 1999-12-30 | 2003-06-17 | カイロン コーポレイション | インターロイキン−２の肺送達のための方法 |
| JP2004515467A (ja) * | 2000-08-07 | 2004-05-27 | ネクター セラピューティックス | 吸入可能な、噴霧乾燥した、最少の凝集物を有する４−ヘリックスバンドルタンパク質粉末 |
| US20040118007A1 (en) * | 2002-12-19 | 2004-06-24 | Acusphere, Inc. | Methods and apparatus for making particles using spray dryer and in-line jet mill |
| US20060084656A1 (en) * | 2004-10-15 | 2006-04-20 | Pfizer Inc. | Compositions and methods for intranasal, buccal, sublingual and pulmonary delivery of varenicline |
| US20080226736A1 (en) * | 2005-10-21 | 2008-09-18 | Eratech S.R.L. | Inhalatory Pharmaceutical Compositions in Form of Dry Powders, Solutions or Suspensions Obtained From the Same and Process for their Preparation |
| US20080286340A1 (en) * | 2007-05-16 | 2008-11-20 | Sven-Borje Andersson | Buffered nicotine containing products |
| US20150283070A1 (en) * | 2014-04-08 | 2015-10-08 | Sansa Corporation (Barbados) Inc. | Nicotine Formulations and Methods of Making the Same |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2231968A1 (en) * | 1998-03-11 | 1999-09-11 | Smoke-Stop, A Partnership Consisting Of Art Slutsky | Method of producing a nicotine medicament |
| JP2001151673A (ja) * | 1999-09-06 | 2001-06-05 | Nikken Chem Co Ltd | 吸入用粉末製剤の製造方法 |
| GB0425758D0 (en) * | 2004-11-23 | 2004-12-22 | Vectura Ltd | Preparation of pharmaceutical compositions |
| FI20060428L (fi) * | 2006-05-03 | 2007-11-04 | Esko Kauppinen | Pintamodifioidut aerosolihiukkaset, menetelmä ja laite niiden tuottamiseksi sekä jauheet ja dispersiot jotka sisältävät kyseisiä hiukkasia |
| GB0801876D0 (en) * | 2008-02-01 | 2008-03-12 | Vectura Group Plc | Suspension formulations |
| US10912334B2 (en) * | 2014-04-28 | 2021-02-09 | Philip Morris Products S.A. | Flavoured nicotine powder inhaler |
| US10149844B2 (en) * | 2015-09-16 | 2018-12-11 | Philip Morris Products S.A. | Inhalable nicotine formulations, and methods of making and using thereof |
| US11224594B2 (en) * | 2015-09-16 | 2022-01-18 | Philip Morris Products S.A. | Nicotine formulations and methods of making and using the same |
| US9585835B1 (en) * | 2015-09-16 | 2017-03-07 | Sansa Corporation (Barbados) Inc. | Inhalable nicotine formulations and methods of making and using the same |
| CA3023630A1 (en) * | 2016-06-30 | 2018-01-04 | Philip Morris Products S.A. | Nicotine particles and compositions |
| BR112018075017A2 (pt) * | 2016-06-30 | 2019-03-19 | Philip Morris Products S.A. | partículas de nicotina |
| IL269275B2 (en) * | 2017-06-28 | 2023-04-01 | Philip Morris Products Sa | Container with particles for use with an inhaler |
-
2017
- 2017-06-14 CA CA3023630A patent/CA3023630A1/en not_active Abandoned
- 2017-06-14 SG SG11201809594WA patent/SG11201809594WA/en unknown
- 2017-06-14 WO PCT/IB2017/053543 patent/WO2018002756A1/en unknown
- 2017-06-14 RU RU2021132299A patent/RU2021132299A/ru unknown
- 2017-06-14 CN CN201780034796.4A patent/CN109310622A/zh active Pending
- 2017-06-14 US US16/309,742 patent/US20190133940A1/en not_active Abandoned
- 2017-06-14 JP JP2018563781A patent/JP2019524648A/ja active Pending
- 2017-06-14 EP EP17732583.4A patent/EP3478264A1/en active Pending
- 2017-06-14 BR BR112018076215-6A patent/BR112018076215A2/pt active Search and Examination
- 2017-06-14 UA UAA201810794A patent/UA124535C2/uk unknown
- 2017-06-14 KR KR1020187035098A patent/KR102523677B1/ko active IP Right Grant
- 2017-06-14 MX MX2018015118A patent/MX2018015118A/es unknown
- 2017-06-14 RU RU2018145313A patent/RU2767064C2/ru active
- 2017-06-14 AU AU2017286864A patent/AU2017286864A1/en not_active Abandoned
- 2017-06-29 TW TW106121799A patent/TW201801716A/zh unknown
- 2017-06-29 AR ARP170101809A patent/AR108920A1/es unknown
-
2018
- 2018-10-18 ZA ZA2018/06949A patent/ZA201806949B/en unknown
- 2018-11-28 IL IL263355A patent/IL263355A/en unknown
- 2018-12-21 PH PH12018502714A patent/PH12018502714A1/en unknown
-
2021
- 2021-08-05 US US17/394,623 patent/US20210361567A1/en active Pending
-
2022
- 2022-03-02 JP JP2022031716A patent/JP2022071106A/ja active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001013893A2 (en) * | 1999-08-25 | 2001-03-01 | Advanced Inhalation Research, Inc. | Use of simple amino acids to form porous particles |
| CN1384733A (zh) * | 1999-10-29 | 2002-12-11 | 吸入治疗系统公司 | 分散性得到改进的干粉组合物 |
| JP2003519175A (ja) * | 1999-12-30 | 2003-06-17 | カイロン コーポレイション | インターロイキン−２の肺送達のための方法 |
| JP2004515467A (ja) * | 2000-08-07 | 2004-05-27 | ネクター セラピューティックス | 吸入可能な、噴霧乾燥した、最少の凝集物を有する４−ヘリックスバンドルタンパク質粉末 |
| US20040118007A1 (en) * | 2002-12-19 | 2004-06-24 | Acusphere, Inc. | Methods and apparatus for making particles using spray dryer and in-line jet mill |
| US20060084656A1 (en) * | 2004-10-15 | 2006-04-20 | Pfizer Inc. | Compositions and methods for intranasal, buccal, sublingual and pulmonary delivery of varenicline |
| US20080226736A1 (en) * | 2005-10-21 | 2008-09-18 | Eratech S.R.L. | Inhalatory Pharmaceutical Compositions in Form of Dry Powders, Solutions or Suspensions Obtained From the Same and Process for their Preparation |
| US20080286340A1 (en) * | 2007-05-16 | 2008-11-20 | Sven-Borje Andersson | Buffered nicotine containing products |
| US20150283070A1 (en) * | 2014-04-08 | 2015-10-08 | Sansa Corporation (Barbados) Inc. | Nicotine Formulations and Methods of Making the Same |
Non-Patent Citations (1)
| Title |
|---|
| HIROKO OTAKE ET AL.: "Inhalable Spray-Freeze-Dried Powder with L-Leucine that Delivers Particles Independent of Inspiratory Flow Pattern and Inhalation Device", 《PHARM. RES.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114828825A (zh) * | 2019-08-30 | 2022-07-29 | 塔克索公司 | 装载的颗粒、其生产方法及其用途 |
| CN115135175A (zh) * | 2019-12-19 | 2022-09-30 | 尤尔实验室有限公司 | 有机基尼古丁凝胶组合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| IL263355A (en) | 2018-12-31 |
| JP2019524648A (ja) | 2019-09-05 |
| TW201801716A (zh) | 2018-01-16 |
| KR20190025824A (ko) | 2019-03-12 |
| RU2021132299A (ru) | 2021-12-10 |
| US20210361567A1 (en) | 2021-11-25 |
| KR102523677B1 (ko) | 2023-04-20 |
| RU2018145313A (ru) | 2020-07-30 |
| US20190133940A1 (en) | 2019-05-09 |
| ZA201806949B (en) | 2019-07-31 |
| AU2017286864A1 (en) | 2018-11-15 |
| MX2018015118A (es) | 2019-04-15 |
| EP3478264A1 (en) | 2019-05-08 |
| JP2022071106A (ja) | 2022-05-13 |
| UA124535C2 (uk) | 2021-10-05 |
| AR108920A1 (es) | 2018-10-10 |
| RU2018145313A3 (zh) | 2020-07-30 |
| WO2018002756A1 (en) | 2018-01-04 |
| PH12018502714A1 (en) | 2019-07-29 |
| RU2767064C2 (ru) | 2022-03-16 |
| BR112018076215A2 (pt) | 2019-03-26 |
| SG11201809594WA (en) | 2018-11-29 |
| CA3023630A1 (en) | 2018-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109310622A (zh) | 尼古丁颗粒和组合物 | |
| CN109310623B (zh) | 尼古丁颗粒 | |
| JP6257562B2 (ja) | ジケトピペラジン及び活性薬剤を含有する微粒子の製剤特性の改善方法 | |
| TWI283182B (en) | Inhalable spray dried 4-helix bundle protein powders having minimized aggregation | |
| JP4482925B2 (ja) | アミノ酸類粉末及びその製造方法 | |
| ES2339423T3 (es) | Composiciones terapeuticas para administracion pulmonar. | |
| CN106619565B (zh) | 精氨酸制剂及其制备方法和应用 | |
| CN113750052B (zh) | 一种乙酰半胱氨酸颗粒及其制备方法 | |
| NZ747471A (en) | Nicotine particles and compositions | |
| WO2013139384A1 (en) | Freezing of aerosolized solutions (fas): a system for continuous particle production | |
| KR20240134314A (ko) | 만성 폐 질환의 치료를 위한 흡입가능한 또는 섭취가능한 락트산 조성물 | |
| WO2023114375A2 (en) | Inhalable or ingestible lactic acid compositions for the treatment of chronic lung disease | |
| AU2013205432B2 (en) | A method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and an active agent | |
| NZ747726A (en) | Nicotine particles |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |