FI111688B - Menetelmä insuliinin terapeuttisen kuivapulverivalmisteen valmistamiseksi - Google Patents

Menetelmä insuliinin terapeuttisen kuivapulverivalmisteen valmistamiseksi Download PDF

Info

Publication number: FI111688B
Authority: FI; Finland
Prior art keywords: insulin; att; eller; förfarande enligt; och
Prior art date: 1993-06-24

Application number

FI956227A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI956227L (fi

FI956227A0 (fi

Inventor

Kjell Goeran Erik Baeckstroem

Carl Magnus Olof Dahlbaeck

Peter Edman

Ann Charlotte Birgit Johansson

Original Assignee

Astra Ab

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1993-06-24

Filing date

1995-12-22

Publication date

2003-09-15

1993-06-24 Priority claimed from SE9302198A external-priority patent/SE9302198D0/xx

1994-02-04 Priority claimed from SE9400370A external-priority patent/SE9400370L/xx

1995-12-22 Application filed by Astra Ab filed Critical Astra Ab

1995-12-22 Publication of FI956227L publication Critical patent/FI956227L/fi

1995-12-22 Publication of FI956227A0 publication Critical patent/FI956227A0/fi

2003-09-15 Application granted granted Critical

2003-09-15 Publication of FI111688B publication Critical patent/FI111688B/fi

Links

NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims abstract description 297
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FIWQZURFGYXCEO-UHFFFAOYSA-M sodium;decanoate Chemical group [Na+].CCCCCCCCCC([O-])=O FIWQZURFGYXCEO-UHFFFAOYSA-M 0.000 claims description 35
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-1 alkyl glycoside Chemical class 0.000 claims description 14
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PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 14
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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 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
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HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 5
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GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 4
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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 3
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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 3
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238000005054 agglomeration Methods 0.000 claims description 3
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 3
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VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 claims description 3
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VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 3
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MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical group 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 claims description 3
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JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].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)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 claims description 2
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WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical class 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)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 claims description 2
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QDIGBJJRWUZARS-UHFFFAOYSA-M potassium;decanoate Chemical compound [K+].CCCCCCCCCC([O-])=O QDIGBJJRWUZARS-UHFFFAOYSA-M 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
230000022558 protein metabolic process Effects 0.000 description 1
239000001397 quillaja saponaria molina bark Substances 0.000 description 1
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230000001105 regulatory effect Effects 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
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BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
229960004025 sodium salicylate Drugs 0.000 description 1
IWQPOPSAISBUAH-VOVMJQHHSA-M sodium;2-[[(2z)-2-[(3r,4s,5s,8s,9s,10s,11r,13r,14s,16s)-16-acetyl-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1h-cyclopenta[a]phenanthren-17-ylidene]-6-methylheptanoyl]amino]ethanesulfonate Chemical compound [Na+].C1C[C@@H](O)[C@@H](C)[C@@H]2CC[C@]3(C)[C@@]4(C)C[C@H](C(C)=O)/C(=C(C(=O)NCCS([O-])(=O)=O)/CCCC(C)C)[C@@H]4C[C@@H](O)[C@H]3[C@]21C IWQPOPSAISBUAH-VOVMJQHHSA-M 0.000 description 1
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239000013638 trimer Substances 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
150000004670 unsaturated fatty acids Chemical class 0.000 description 1
235000021122 unsaturated fatty acids Nutrition 0.000 description 1
229940014499 ursodeoxycholate Drugs 0.000 description 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 description 1
210000005166 vasculature Anatomy 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
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin

Landscapes

Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Endocrinology (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Immunology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Pulmonology (AREA)
Otolaryngology (AREA)
Oil, Petroleum & Natural Gas (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Emergency Medicine (AREA)
Hematology (AREA)
Obesity (AREA)
Medicinal Preparation (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)

FI956227A 1993-06-24 1995-12-22 Menetelmä insuliinin terapeuttisen kuivapulverivalmisteen valmistamiseksi FI111688B (fi)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
SE9302198A SE9302198D0 (sv)	1993-06-24	1993-06-24	Powder preparation for inhalation
SE9302198		1993-06-24
SE9400370		1994-02-04
SE9400370A SE9400370L (sv)	1994-02-04	1994-02-04	Terapeutisk komposition för inhalation
SE9400633		1994-06-23
PCT/SE1994/000633 WO1995000127A1 (en)	1993-06-24	1994-06-23	Therapeutic preparation for inhalation

Publications (3)

Publication Number	Publication Date
FI956227L FI956227L (fi)	1995-12-22
FI956227A0 FI956227A0 (fi)	1995-12-22
FI111688B true FI111688B (fi)	2003-09-15

Family

ID=26661778

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI956227A FI111688B (fi)	1993-06-24	1995-12-22	Menetelmä insuliinin terapeuttisen kuivapulverivalmisteen valmistamiseksi

Country Status (32)

Country	Link
US (3)	US5518998C1 (pl)
EP (1)	EP0706382B1 (pl)
JP (2)	JP3874789B2 (pl)
KR (1)	KR100372673B1 (pl)
CN (1)	CN1110301C (pl)
AT (1)	ATE183920T1 (pl)
AU (1)	AU692780B2 (pl)
BR (1)	BR9406907A (pl)
CA (1)	CA2166108C (pl)
CZ (1)	CZ287314B6 (pl)
DE (1)	DE69420412T2 (pl)
DK (1)	DK0706382T3 (pl)
EE (1)	EE03221B1 (pl)
EG (1)	EG20599A (pl)
ES (1)	ES2138087T3 (pl)
FI (1)	FI111688B (pl)
GR (1)	GR3031974T3 (pl)
HK (1)	HK1009584A1 (pl)
HU (1)	HU228129B1 (pl)
IL (1)	IL110084A (pl)
IS (1)	IS1768B (pl)
MX (1)	MX9404761A (pl)
MY (1)	MY112098A (pl)
NO (1)	NO313657B1 (pl)
NZ (1)	NZ268137A (pl)
PL (1)	PL178403B1 (pl)
RU (1)	RU2148398C1 (pl)
SA (1)	SA94150030B1 (pl)
SK (1)	SK283145B6 (pl)
TW (1)	TW402506B (pl)
UA (1)	UA49794C2 (pl)
WO (1)	WO1995000127A1 (pl)

Families Citing this family (212)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5645820A (en) *	1987-06-24	1997-07-08	Autoimmune, Inc.	Treatment of autoimmune diseases by aerosol administration of autoantigens
US6645504B1 (en)	1987-06-24	2003-11-11	Autoimmune Inc.	Bystander suppression of type I diabetes by oral administration of glucagon
IL99699A (en) *	1990-10-10	2002-04-21	Autoimmune Inc	Drug with the option of oral, intra-intestinal, or inhaled dosing for suppression of autoimmune response associated with type I diabetes
US6582728B1 (en) *	1992-07-08	2003-06-24	Inhale Therapeutic Systems, Inc.	Spray drying of macromolecules to produce inhaleable dry powders
US6509006B1 (en)	1992-07-08	2003-01-21	Inhale Therapeutic Systems, Inc.	Devices compositions and methods for the pulmonary delivery of aerosolized medicaments
DE69332105T2 (de)	1992-09-29	2003-03-06	Inhale Therapeutic Systems, San Carlos	Pulmonale abgabe von aktiven fragmenten des parathormons
EP1607086A1 (en) *	1993-01-29	2005-12-21	Aradigm Corporation	Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin
US6131567A (en) *	1993-01-29	2000-10-17	Aradigm Corporation	Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin
US6024090A (en) *	1993-01-29	2000-02-15	Aradigm Corporation	Method of treating a diabetic patient by aerosolized administration of insulin lispro
US7448375B2 (en) *	1993-01-29	2008-11-11	Aradigm Corporation	Method of treating diabetes mellitus in a patient
US5747445A (en) *	1993-06-24	1998-05-05	Astra Aktiebolag	Therapeutic preparation for inhalation
TW402506B (en) *	1993-06-24	2000-08-21	Astra Ab	Therapeutic preparation for inhalation
US6794357B1 (en) *	1993-06-24	2004-09-21	Astrazeneca Ab	Compositions for inhalation
IS1796B (is) *	1993-06-24	2001-12-31	Ab Astra	Fjölpeptíð lyfjablanda til innöndunar sem einnig inniheldur eykjaefnasamband
US20010003739A1 (en) *	1993-06-24	2001-06-14	Astrazeneca Ab	Systemic administration of a therapeutic preparation
US6632456B1 (en) *	1993-06-24	2003-10-14	Astrazeneca Ab	Compositions for inhalation
US5830853A (en) *	1994-06-23	1998-11-03	Astra Aktiebolag	Systemic administration of a therapeutic preparation
GB9322014D0 (en)	1993-10-26	1993-12-15	Co Ordinated Drug Dev	Improvements in and relating to carrier particles for use in dry powder inhalers
US6051256A (en)	1994-03-07	2000-04-18	Inhale Therapeutic Systems	Dispersible macromolecule compositions and methods for their preparation and use
KR100419037B1 (ko)	1994-03-07	2004-06-12	넥타르 테라퓨틱스	폐를통한인슐린의전달방법및그조성물
US6165976A (en)	1994-06-23	2000-12-26	Astra Aktiebolag	Therapeutic preparation for inhalation
US6586006B2 (en)	1994-08-04	2003-07-01	Elan Drug Delivery Limited	Solid delivery systems for controlled release of molecules incorporated therein and methods of making same
US6290991B1 (en)	1994-12-02	2001-09-18	Quandrant Holdings Cambridge Limited	Solid dose delivery vehicle and methods of making same
SE9404468D0 (sv) *	1994-12-22	1994-12-22	Astra Ab	Powder formulations
EE9700136A (et) *	1994-12-22	1997-12-15	Astra Aktiebolag	Paratüroidhormooni PTH sisaldav ravimpreparaat inhaleerimiseks
US6524557B1 (en)	1994-12-22	2003-02-25	Astrazeneca Ab	Aerosol formulations of peptides and proteins
CA2206782C (en)	1994-12-22	2007-04-03	Astra Aktiebolag	Aerosol drug formulations
GB9501841D0 (en)	1995-01-31	1995-03-22	Co Ordinated Drug Dev	Improvements in and relating to carrier particles for use in dry powder inhalers
US5612053A (en)	1995-04-07	1997-03-18	Edward Mendell Co., Inc.	Controlled release insufflation carrier for medicaments
GB9508691D0 (en) *	1995-04-28	1995-06-14	Pafra Ltd	Stable compositions
US6428771B1 (en) *	1995-05-15	2002-08-06	Pharmaceutical Discovery Corporation	Method for drug delivery to the pulmonary system
US5714007A (en) *	1995-06-06	1998-02-03	David Sarnoff Research Center, Inc.	Apparatus for electrostatically depositing a medicament powder upon predefined regions of a substrate
US5669973A (en) *	1995-06-06	1997-09-23	David Sarnoff Research Center, Inc.	Apparatus for electrostatically depositing and retaining materials upon a substrate
US5654007A (en) *	1995-06-07	1997-08-05	Inhale Therapeutic Systems	Methods and system for processing dispersible fine powders
GB9515182D0 (en)	1995-07-24	1995-09-20	Co Ordinated Drug Dev	Improvements in and relating to powders for use in dry powder inhalers
US5642727A (en) *	1995-07-25	1997-07-01	David Sarnoff Research Center, Inc.	Inhaler apparatus using a tribo-electric charging technique
US5985309A (en) *	1996-05-24	1999-11-16	Massachusetts Institute Of Technology	Preparation of particles for inhalation
US5874064A (en)	1996-05-24	1999-02-23	Massachusetts Institute Of Technology	Aerodynamically light particles for pulmonary drug delivery
USRE37053E1 (en)	1996-05-24	2001-02-13	Massachusetts Institute Of Technology	Particles incorporating surfactants for pulmonary drug delivery
US6254854B1 (en)	1996-05-24	2001-07-03	The Penn Research Foundation	Porous particles for deep lung delivery
US5855913A (en) *	1997-01-16	1999-01-05	Massachusetts Instite Of Technology	Particles incorporating surfactants for pulmonary drug delivery
US6503480B1 (en)	1997-05-23	2003-01-07	Massachusetts Institute Of Technology	Aerodynamically light particles for pulmonary drug delivery
US6652837B1 (en)	1996-05-24	2003-11-25	Massachusetts Institute Of Technology	Preparation of novel particles for inhalation
US20020052310A1 (en) *	1997-09-15	2002-05-02	Massachusetts Institute Of Technology The Penn State Research Foundation	Particles for inhalation having sustained release properties
US5871010A (en) *	1996-06-10	1999-02-16	Sarnoff Corporation	Inhaler apparatus with modified surfaces for enhanced release of dry powders
US5857456A (en) *	1996-06-10	1999-01-12	Sarnoff Corporation	Inhaler apparatus with an electronic means for enhanced release of dry powders
US20030203036A1 (en) *	2000-03-17	2003-10-30	Gordon Marc S.	Systems and processes for spray drying hydrophobic drugs with hydrophilic excipients
US6043214A (en) *	1997-03-20	2000-03-28	Novo Nordisk A/S	Method for producing powder formulation comprising an insulin
US6310038B1 (en)	1997-03-20	2001-10-30	Novo Nordisk A/S	Pulmonary insulin crystals
CO4750643A1 (es) *	1997-06-13	1999-03-31	Lilly Co Eli	Formulacion estable de la insulina que contiene l-arginina y protamina
US7052678B2 (en)	1997-09-15	2006-05-30	Massachusetts Institute Of Technology	Particles for inhalation having sustained release properties
US6433040B1 (en)	1997-09-29	2002-08-13	Inhale Therapeutic Systems, Inc.	Stabilized bioactive preparations and methods of use
US20060165606A1 (en)	1997-09-29	2006-07-27	Nektar Therapeutics	Pulmonary delivery particles comprising water insoluble or crystalline active agents
US6946117B1 (en) *	1997-09-29	2005-09-20	Nektar Therapeutics	Stabilized preparations for use in nebulizers
US20020017295A1 (en) *	2000-07-07	2002-02-14	Weers Jeffry G.	Phospholipid-based powders for inhalation
US6565885B1 (en)	1997-09-29	2003-05-20	Inhale Therapeutic Systems, Inc.	Methods of spray drying pharmaceutical compositions
US6309623B1 (en)	1997-09-29	2001-10-30	Inhale Therapeutic Systems, Inc.	Stabilized preparations for use in metered dose inhalers
US20010053761A1 (en) *	1998-01-08	2001-12-20	Dimarchi Richard Dennis	Method for administering aspb28-human insulin
US7070799B1 (en) *	1998-02-10	2006-07-04	Generex Pharmaceuticals, Inc.	Method for administering insulin to the buccal region
US6221378B1 (en)	1998-02-10	2001-04-24	Generex Pharmaceuticals Incorporated	Mixed micellar delivery system and method of preparation
US6149774A (en)	1998-06-10	2000-11-21	Delsys Pharmaceutical Corporation	AC waveforms biasing for bead manipulating chucks
US6451349B1 (en)	1998-08-19	2002-09-17	Quadrant Healthcare (Uk) Limited	Spray-drying process for the preparation of microparticles
US6956021B1 (en) *	1998-08-25	2005-10-18	Advanced Inhalation Research, Inc.	Stable spray-dried protein formulations
US6294153B1 (en)	1998-12-21	2001-09-25	Generex Pharmaceuticals, Inc.	Aerosol pharmaceutical formulation for pulmonary and nasal delivery
US20040214747A1 (en) *	1999-01-06	2004-10-28	Dimarchi Richard Dennis	Method for administering monomeric insulin
AU2879100A (en) *	1999-02-12	2000-08-29	Miles A. Libbey Iii	Formulation and system for intra-oral delivery of pharmaceutical agents
US7658938B2 (en)	1999-02-22	2010-02-09	Merrion Reasearch III Limited	Solid oral dosage form containing an enhancer
US6350432B1 (en)	1999-03-19	2002-02-26	Generex Pharmaceuticals Incorporated	Pressurized container having an aerosolized pharmaceutical composition
US6923979B2 (en)	1999-04-27	2005-08-02	Microdose Technologies, Inc.	Method for depositing particles onto a substrate using an alternating electric field
EP1187639A1 (en)	1999-06-04	2002-03-20	Delrx Pharmaceutical Corporation	Formulations comprising dehydrated particles of pharmaceutical agents and process for preparing the same
US7169889B1 (en) *	1999-06-19	2007-01-30	Biocon Limited	Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin
US6858199B1 (en)	2000-06-09	2005-02-22	Advanced Inhalation Research, Inc.	High efficient delivery of a large therapeutic mass aerosol
US9006175B2 (en) *	1999-06-29	2015-04-14	Mannkind Corporation	Potentiation of glucose elimination
EP2280020B1 (en) *	1999-06-29	2016-02-17	MannKind Corporation	Pharmaceutical formulations comprising a peptide complexed with a diketopiperazine
US6749835B1 (en)	1999-08-25	2004-06-15	Advanced Inhalation Research, Inc.	Formulation for spray-drying large porous particles
US20010036481A1 (en) *	1999-08-25	2001-11-01	Advanced Inhalation Research, Inc.	Modulation of release from dry powder formulations
US7678364B2 (en)	1999-08-25	2010-03-16	Alkermes, Inc.	Particles for inhalation having sustained release properties
CA2382821A1 (en) *	1999-08-25	2001-03-01	Advanced Inhalation Research, Inc.	Modulation of release from dry powder formulations
WO2001051030A1 (en)	2000-01-10	2001-07-19	Dura Pharmaceuticals, Inc.	Pharmaceutical formulation and method for pulmonary and oral delivery
JP2001240558A (ja) *	2000-02-29	2001-09-04	Nippon Suisan Kaisha Ltd	多価不飽和脂肪酸を経粘膜吸収促進剤として含有する固形製剤。
GB0004827D0 (en) *	2000-02-29	2000-04-19	Quadrant Holdings Cambridge	Compositions
GB0008660D0 (en) *	2000-04-07	2000-05-31	Arakis Ltd	The treatment of respiratory diseases
US7871598B1 (en)	2000-05-10	2011-01-18	Novartis Ag	Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use
MXPA02001323A (es) *	2000-05-10	2004-07-16	Alliance Pharma	Microgranulos con base fosfolipida para la liberacion de farmaco.
US8404217B2 (en)	2000-05-10	2013-03-26	Novartis Ag	Formulation for pulmonary administration of antifungal agents, and associated methods of manufacture and use
GB0011807D0 (en) *	2000-05-16	2000-07-05	Quadrant Holdings Cambridge	Formulation for inhalation
US7575761B2 (en) *	2000-06-30	2009-08-18	Novartis Pharma Ag	Spray drying process control of drying kinetics
US6444619B1 (en)	2000-09-28	2002-09-03	Rohm And Haas Company	Delivery system for cyclopropenes
US6953540B2 (en)	2000-09-29	2005-10-11	Rohm And Haas Company	Continuous process for the preparation of encapsulated cyclopropenes
IL145476A (en)	2000-09-29	2006-07-05	Rohm & Haas	Cyclopropene release systems that require less water
IT1319201B1 (it) *	2000-10-12	2003-09-26	Nicox Sa	Farmaci per il diabete.
DE60137452D1 (de) *	2000-11-29	2009-03-05	Itoham Foods Inc	Pulverzubereitungen und verfahren zu ihrer herstellung
EP2168571B1 (en) *	2000-11-30	2018-08-22	Vectura Limited	Particles for use in a Pharmaceutical Composition
US8048451B2 (en)	2000-11-30	2011-11-01	Vectura Limited	Pharmaceutical compositions for inhalation
WO2002051428A1 (fr) *	2000-12-25	2002-07-04	Shiseido Company, Ltd.	Composition de parfum stimulant le systeme sympathique
US20020141946A1 (en) *	2000-12-29	2002-10-03	Advanced Inhalation Research, Inc.	Particles for inhalation having rapid release properties
JP2005504715A (ja)	2000-12-29	2005-02-17	アドバンストインハレーションリサーチ，インコーポレイテッド	持続放出特性を有する吸入用粒子
US6867183B2 (en) *	2001-02-15	2005-03-15	Nobex Corporation	Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith
US7060675B2 (en) *	2001-02-15	2006-06-13	Nobex Corporation	Methods of treating diabetes mellitus
CA2445944A1 (en) *	2001-05-04	2002-11-14	Pfizer Products Inc.	Method of preventing type 2 diabetes with aerosolized insulin
US7713932B2 (en)	2001-06-04	2010-05-11	Biocon Limited	Calcitonin drug-oligomer conjugates, and uses thereof
US6858580B2 (en) *	2001-06-04	2005-02-22	Nobex Corporation	Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US6835802B2 (en) *	2001-06-04	2004-12-28	Nobex Corporation	Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties
US6828305B2 (en) *	2001-06-04	2004-12-07	Nobex Corporation	Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US6828297B2 (en) *	2001-06-04	2004-12-07	Nobex Corporation	Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US6713452B2 (en) *	2001-06-04	2004-03-30	Nobex Corporation	Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
GB0114033D0 (en) *	2001-06-09	2001-08-01	Innovata Biomed Ltd	Process
GB0208742D0 (en)	2002-04-17	2002-05-29	Bradford Particle Design Ltd	Particulate materials
US7312192B2 (en) *	2001-09-07	2007-12-25	Biocon Limited	Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
US7196059B2 (en) *	2001-09-07	2007-03-27	Biocon Limited	Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith
US6913903B2 (en) *	2001-09-07	2005-07-05	Nobex Corporation	Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
US7166571B2 (en) *	2001-09-07	2007-01-23	Biocon Limited	Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
US6770625B2 (en)	2001-09-07	2004-08-03	Nobex Corporation	Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith
US7030082B2 (en) *	2001-09-07	2006-04-18	Nobex Corporation	Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith
EP1992335A1 (en)	2001-11-01	2008-11-19	Nektar Therapeutics	Spray drying methods and compositions thereof
WO2003043585A2 (en)	2001-11-20	2003-05-30	Advanced Inhalation Research, Inc.	Improved particulate compositions for pulmonary delivery
AU2002346472A1 (en) *	2001-11-20	2003-06-10	Advanced Inhalation Research, Inc.	Particulate compositions for improving solubility of poorly soluble agents
SI1458360T1 (sl) *	2001-12-19	2011-08-31	Novartis Ag	Pulmonalno dajanje aminoglikozidov
ES2300568T3 (es)	2002-03-20	2008-06-16	Mannkind Corporation	Aparato de inhalacion.
US7582284B2 (en)	2002-04-17	2009-09-01	Nektar Therapeutics	Particulate materials
AU2003226603A1 (en) *	2002-04-19	2003-11-03	Yissum Research Development Company Of The Hebrew University Of Jerusalem	Beta-agonist compounds comprising nitric oxide donor groups and reactive oxygen species scavenger groups and their use in the treatment of respiratory disorders
GB0216562D0 (en) *	2002-04-25	2002-08-28	Bradford Particle Design Ltd	Particulate materials
US9339459B2 (en)	2003-04-24	2016-05-17	Nektar Therapeutics	Particulate materials
WO2003105768A2 (en) *	2002-06-13	2003-12-24	Nobex Corporation	Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus
DE10234165B4 (de) *	2002-07-26	2008-01-03	Advanced Micro Devices, Inc., Sunnyvale	Verfahren zum Füllen eines Grabens, der in einem Substrat gebildet ist, mit einem isolierenden Material
CN1694689A (zh) *	2002-09-30	2005-11-09	阿库斯菲尔公司	供吸入的缓释多孔微粒
WO2004037843A2 (en) *	2002-10-25	2004-05-06	Yissum Research Development Company Of The Hebrew University Of Jerusalem	Steroid compounds comprising superoxide dismutase mimic groups and nitric oxide donor groups, and their use in the preparation of medicaments
US20040121003A1 (en) *	2002-12-19	2004-06-24	Acusphere, Inc.	Methods for making pharmaceutical formulations comprising deagglomerated microparticles
US6962006B2 (en) *	2002-12-19	2005-11-08	Acusphere, Inc.	Methods and apparatus for making particles using spray dryer and in-line jet mill
CN1311868C (zh) *	2003-06-10	2007-04-25	上海兴康医药研究开发有限公司	一种胰岛素干粉吸入剂的制备方法
US8921311B2 (en)	2003-08-01	2014-12-30	Mannkind Corporation	Method for treating hyperglycemia
KR101152470B1 (ko) *	2003-08-13	2012-06-01	바이오콘 리미티드	치료제용 마이크로-입자 지방산 염 고형 투약 제형
ATE498394T1 (de) *	2003-09-02	2011-03-15	Norton Healthcare Ltd	Verfahren zur herstellung eines medikaments
US20080118442A1 (en) *	2003-09-10	2008-05-22	Map Pharmaceuticals, Inc.	Aerosol Formulations for Delivery of Dihydroergotamine to the Systemic Circulations Via Pulmonary Inhalation
US7338171B2 (en) *	2003-10-27	2008-03-04	Jen-Chuen Hsieh	Method and apparatus for visual drive control
US20050153874A1 (en) *	2004-01-12	2005-07-14	Mannkind Corporation	Method of reducing serum proinsulin levels in type 2 diabetics
US20080090753A1 (en)	2004-03-12	2008-04-17	Biodel, Inc.	Rapid Acting Injectable Insulin Compositions
ES2328048T3 (es) *	2004-03-12	2009-11-06	Biodel, Inc.	Composiciones de insulina con absorcion mejorada.
WO2005092301A1 (en) *	2004-03-26	2005-10-06	Universita' Degli Studi Di Parma	Insulin highly respirable microparticles
US20070219131A1 (en) *	2004-04-15	2007-09-20	Ben-Sasson Shmuel A	Compositions capable of facilitating penetration across a biological barrier
MXPA06011871A (es) *	2004-04-15	2007-10-08	Chiasma Inc	Composiciones capaces de facilitar la penetracion a traves de una barrera biologica.
KR20120089705A (ko)	2004-04-23	2012-08-13	사이덱스 파마슈티칼스, 인크.	술포알킬 에테르 시클로덱스트린 함유 ｄｐｉ 제형
CN101027318B (zh) *	2004-07-19	2016-05-25	比奥孔有限公司	胰岛素-低聚物共轭物，制剂及其用途
BRPI0514263B8 (pt)	2004-08-20	2021-05-25	Mannkind Corp	método para a síntese de bis-3,6-[4-aminobutil]-2,5-dicetopiperazina n-protegida
KR101306384B1 (ko)	2004-08-23	2013-09-09	맨카인드 코포레이션	약물 전달용 디케토피페라진염, 디케토모르포린염 또는디케토디옥산염
GB0425758D0 (en)	2004-11-23	2004-12-22	Vectura Ltd	Preparation of pharmaceutical compositions
MX381952B (es)	2005-09-14	2025-03-13	Mannkind Corp	Metodo para formulacion de farmaco basado en el aumento de la afinidad de agentes activos hacia las superficies de microparticulas cristalinas.
US8084420B2 (en) *	2005-09-29	2011-12-27	Biodel Inc.	Rapid acting and long acting insulin combination formulations
WO2007041481A1 (en) *	2005-09-29	2007-04-12	Biodel, Inc.	Rapid acting and prolonged acting insulin preparations
US7713929B2 (en)	2006-04-12	2010-05-11	Biodel Inc.	Rapid acting and long acting insulin combination formulations
MX2008004674A (es) *	2005-10-13	2008-11-12	Biocon Ltd	Proceso para la preparacion de conjugados de insulina.
US7629331B2 (en)	2005-10-26	2009-12-08	Cydex Pharmaceuticals, Inc.	Sulfoalkyl ether cyclodextrin compositions and methods of preparation thereof
NZ567601A (en) *	2005-11-30	2010-12-24	Generex Pharm Inc	Orally absorbed pharmaceutical formulation and method of administration
EP1978933A2 (en) *	2005-12-15	2008-10-15	Acusphere, Inc.	Processes for making particle-based pharmaceutical formulations for oral administration
TWI299993B (en)	2005-12-15	2008-08-21	Dev Center Biotechnology	Aqueous inhalation pharmaceutical composition
EP1973523A2 (en) *	2005-12-15	2008-10-01	Acusphere, Inc.	Processes for making particle-based pharmaceutical formulations for pulmonary or nasal administration
JP5599975B2 (ja)	2006-02-22	2014-10-01	マンカインドコーポレイション	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
WO2007098507A2 (en)	2006-02-24	2007-08-30	Rigel Pharmaceuticals, Inc.	Compositions and methods for inhibition of the jak pathway
WO2007117706A2 (en)	2006-04-07	2007-10-18	Merrion Research Iii Limited	Solid oral dosage form containing an enhancer
CA2649109A1 (en) *	2006-04-12	2007-10-25	Biodel, Inc.	Rapid acting and long acting insulin combination formulations
MX2009008582A (es)	2007-02-11	2009-10-30	Map Pharmaceuticals Inc	Metodo para la administracion terapeutica de dihidroergotamina para permitir un rapido alivio de la migraña mientras se minimiza el perfil de efectos secundarios.
WO2008124522A2 (en) *	2007-04-04	2008-10-16	Biodel, Inc.	Amylin formulations
KR100785656B1 (ko)	2007-05-14	2007-12-17	재단법인서울대학교산학협력재단	소염제로 사용되는 소디움글리코콜레이트 또는 그 유도체
CN101939023B (zh) *	2007-10-16	2016-08-03	百康有限公司	可经口给药的固体药物组合物及其方法
DK2211842T3 (en)	2007-10-24	2015-09-21	Mannkind Corp	An inhalable dry powder formulation COMPREHENSIVE GLP-1 FOR USE IN THE TREATMENT OF HYPERGLYCAEMIA AND DIABETES BY pulmonary delivery
WO2011163272A1 (en)	2010-06-21	2011-12-29	Mannkind Corporation	Dry powder drug delivery system and methods
US8785396B2 (en)	2007-10-24	2014-07-22	Mannkind Corporation	Method and composition for treating migraines
ES2394589T3 (es)	2007-12-14	2013-02-04	Aerodesigns, Inc	Suministro de productos alimenticios transformables en aerosol
US20090271021A1 (en) *	2008-04-28	2009-10-29	Popp Shane M	Execution system for the monitoring and execution of insulin manufacture
EP2288369B1 (en)	2008-05-07	2014-07-09	Merrion Research III Limited	Compositions of gnrh related compounds and processes of preparation
US8485180B2 (en)	2008-06-13	2013-07-16	Mannkind Corporation	Dry powder drug delivery system
KR101762089B1 (ko)	2008-06-13	2017-07-26	맨카인드 코포레이션	건조 분말 흡입기 및 약물 투여 시스템
ES2421385T3 (es)	2008-06-20	2013-09-02	Mannkind Corp	Aparato interactivo y procedimiento para establecer el perfil, en tiempo real, de esfuerzos de inhalación
TWI614024B (zh)	2008-08-11	2018-02-11	曼凱公司	超快起作用胰島素之用途
CN102176900B (zh)	2008-09-17	2017-09-26	克艾思马有限公司	药物组合物和相关的给药方法
US8314106B2 (en)	2008-12-29	2012-11-20	Mannkind Corporation	Substituted diketopiperazine analogs for use as drug delivery agents
ES2529100T3 (es)	2009-01-08	2015-02-16	Mannkind Corporation	Tratamiento de la hiperglucemia con GLP-1
PE20150621A1 (es)	2009-01-23	2015-05-07	Rigel Pharmaceuticals Inc	Derivados de 2,4-diamino-pirimidina n2, n4-disustituidos como inhibidores de jak3
US9060927B2 (en)	2009-03-03	2015-06-23	Biodel Inc.	Insulin formulations for rapid uptake
US8538707B2 (en)	2009-03-11	2013-09-17	Mannkind Corporation	Apparatus, system and method for measuring resistance of an inhaler
US20100310660A1 (en) *	2009-06-08	2010-12-09	Taipei Medical University	Dry powder microparticles for pulmonary delivery
MX2011013312A (es)	2009-06-12	2012-01-25	Mankind Corp	Microparticulas de dicetopiperazina con areas de superficie especificas definidas.
EP2496295A1 (en)	2009-11-03	2012-09-12	MannKind Corporation	An apparatus and method for simulating inhalation efforts
JP2013518097A (ja)	2010-01-26	2013-05-20	イッサムリサーチディヴェロップメントカンパニーオブザヘブリューユニバーシティーオブエルサレムエルティーディー	肺高血圧を予防および治療するための組成物および方法
WO2011120033A1 (en)	2010-03-26	2011-09-29	Merrion Research Iii Limited	Pharmaceutical compositions of selective factor xa inhibitors for oral administration
US8802114B2 (en)	2011-01-07	2014-08-12	Merrion Research Iii Limited	Pharmaceutical compositions of iron for oral administration
ES2625858T3 (es)	2011-04-01	2017-07-20	Mannkind Corporation	Paquete de tipo blíster para cartuchos farmacéuticos
WO2012174472A1 (en)	2011-06-17	2012-12-20	Mannkind Corporation	High capacity diketopiperazine microparticles
CN103945859A (zh)	2011-10-24	2014-07-23	曼金德公司	用于治疗疼痛的方法和组合物
JP6231548B2 (ja)	2012-03-23	2017-11-15	マテオンセラピューティクス，インコーポレイテッド	カテプシンの阻害のための組成物および方法
CN108057154B (zh)	2012-07-12	2021-04-16	曼金德公司	干粉药物输送系统和方法
WO2014066856A1 (en)	2012-10-26	2014-05-01	Mannkind Corporation	Inhalable influenza vaccine compositions and methods
US9757395B2 (en)	2012-12-20	2017-09-12	Otitopic Inc.	Dry powder inhaler and methods of use
US9757529B2 (en)	2012-12-20	2017-09-12	Otitopic Inc.	Dry powder inhaler and methods of use
WO2014144895A1 (en)	2013-03-15	2014-09-18	Mannkind Corporation	Microcrystalline diketopiperazine compositions and methods
GB201305825D0 (en)	2013-03-28	2013-05-15	Vectura Ltd	New use
EP3607941A1 (en)	2013-04-30	2020-02-12	Otitopic Inc.	Dry powder formulations and methods of use
EP3021834A1 (en)	2013-07-18	2016-05-25	MannKind Corporation	Heat-stable dry powder pharmaceutical compositions and methods
EP3030294B1 (en)	2013-08-05	2020-10-07	MannKind Corporation	Insufflation apparatus
JP6701086B2 (ja)	2014-02-20	2020-05-27	オティトピックインコーポレイテッド	吸入用の乾燥粉末製剤
WO2015148905A1 (en)	2014-03-28	2015-10-01	Mannkind Corporation	Use of ultrarapid acting insulin
US10561806B2 (en)	2014-10-02	2020-02-18	Mannkind Corporation	Mouthpiece cover for an inhaler
EP3250191B1 (en)	2015-01-29	2024-01-17	Novo Nordisk A/S	Tablets comprising glp-1 agonist and enteric coating
MA41462A (fr)	2015-02-03	2021-05-12	Chiasma Inc	Méthode de traitement de maladies
WO2017193110A1 (en) *	2016-05-06	2017-11-09	Stites Adam	Cannabinoid compositions for sublingual spray nebulizer
WO2019201712A1 (en)	2018-04-16	2019-10-24	Ioulia Tseti	A pharmaceutical dry powder composition for inhalation comprising a thyroid hormone
US20220000880A1 (en)	2018-11-01	2022-01-06	Rigel Pharmaceuticals, Inc.	Method and composition embodiments for treating acute myeloid leukemia
US20200377518A1 (en)	2019-05-29	2020-12-03	Rigel Pharmaceuticals, Inc.	Method of preventing and treating thrombosis
WO2021026451A1 (en)	2019-08-08	2021-02-11	Rigel Pharmaceuticals, Inc.	Compounds and method for treating cytokine release syndrome
CN114286679A (zh)	2019-08-14	2022-04-05	里格尔药品股份有限公司	阻断或改善细胞因子释放综合征的方法
US11141457B1 (en)	2020-12-28	2021-10-12	Amryt Endo, Inc.	Oral octreotide therapy and contraceptive methods
US20230303555A1 (en)	2022-03-23	2023-09-28	Rigel Pharmaceuticals, Inc.	Pyrimid-2-yl-pyrazole compounds as irak inhibitors

Family Cites Families (76)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE556587A (pl)	1957-01-31	1957-04-11
GB1527605A (en) *	1975-08-20	1978-10-04	Takeda Chemical Industries Ltd	Insulin preparation for intranasal administration
JPS6034925B2 (ja)	1979-07-31	1985-08-12	帝人株式会社	持続性鼻腔用製剤およびその製造法
JPS5795920A (en)	1980-12-04	1982-06-15	Teijin Ltd	Remedy for respiratory disease
US4900730A (en) *	1981-01-14	1990-02-13	Toyo Jozo Co., Ltd.	Preparation which promotes the absorption of peptides
DE3274065D1 (de) *	1981-07-08	1986-12-11	Draco Ab	Powder inhalator
SE438261B (sv) *	1981-07-08	1985-04-15	Draco Ab	Anvendning i dosinhalator av ett perforerat membran
US5260306A (en)	1981-07-24	1993-11-09	Fisons Plc	Inhalation pharmaceuticals
JPS59163313A (ja) *	1983-03-09	1984-09-14	Teijin Ltd	経鼻投与用ペプチドホルモン類組成物
US4746508A (en) *	1983-06-06	1988-05-24	Beth Israel Hospital Assn.	Drug administration
US4548922A (en) *	1983-06-06	1985-10-22	Beth Israel Hospital	Drug administration
US4959358A (en) *	1983-06-06	1990-09-25	Beth Israel Hospital Assn.	Drug administration
US4963367A (en)	1984-04-27	1990-10-16	Medaphore, Inc.	Drug delivery compositions and methods
US5288498A (en)	1985-05-01	1994-02-22	University Of Utah Research Foundation	Compositions of oral nondissolvable matrixes for transmucosal administration of medicaments
JPS61267528A (ja) *	1984-11-26	1986-11-27	Yamanouchi Pharmaceut Co Ltd	吸収促進剤を含有するカルシトニン経鼻剤
SE448277B (sv) *	1985-04-12	1987-02-09	Draco Ab	Indikeringsanordning vid en doseringsanordning for lekemedel
EP0200383A3 (en)	1985-04-15	1987-09-02	Eli Lilly And Company	An improved method for administering insulin
US5122127A (en)	1985-05-01	1992-06-16	University Of Utah	Apparatus and methods for use in administering medicaments by direct medicament contact to mucosal tissues
EP0223831B1 (en)	1985-05-22	1992-07-15	Liposome Technology, Inc.	Liposome inhalation method and system
US4847298A (en)	1985-08-16	1989-07-11	Merck & Co., Inc.	Acylcarnitines as absorption-enhancing agents for drug delivery through mucous membranes of the nasal, buccal, sublingual and vaginal compartments
IL77186A0 (en) *	1985-11-29	1986-04-29	Touitou Elka	Pharmaceutical insulin composition
SE453566B (sv) *	1986-03-07	1988-02-15	Draco Ab	Anordning vid pulverinhalatorer
JPS632932A (ja)	1986-06-23	1988-01-07	Teijin Ltd	経鼻投与用粉末状組成物
WO1988001165A1 (en)	1986-08-11	1988-02-25	Innovata Biomed Limited	Pharmaceutical formulations comprising microcapsules
US5179079A (en) *	1986-12-16	1993-01-12	Novo Nordisk A/S	Nasal formulation and intranasal administration therewith
NZ222907A (en) *	1986-12-16	1990-08-28	Novo Industri As	Preparation for intranasal administration containing a phospholipid absorption enhancing system
GB8712176D0 (en) *	1987-05-22	1987-06-24	Cosmas Damian Ltd	Drug delivery system
JPH01117825A (ja)	1987-10-28	1989-05-10	Sanwa Kagaku Kenkyusho Co Ltd	鼻くう、副鼻くう投与用製剤及びその使用方法並びにその形状及び使用器具
EP0360340A1 (en) *	1988-09-19	1990-03-28	Akzo N.V.	Composition for nasal administration containing a peptide
US5997856A (en) *	1988-10-05	1999-12-07	Chiron Corporation	Method and compositions for solubilization and stabilization of polypeptides, especially proteins
SE8803935L (sv) *	1988-10-31	1990-05-01	Kabivitrum Ab	Laekemedelskomposition
US5006343A (en)	1988-12-29	1991-04-09	Benson Bradley J	Pulmonary administration of pharmaceutically active substances
GB8900267D0 (en)	1989-01-06	1989-03-08	Riker Laboratories Inc	Narcotic analgesic formulations and apparatus containing same
US4994439A (en)	1989-01-19	1991-02-19	California Biotechnology Inc.	Transmembrane formulations for drug administration
US5011678A (en)	1989-02-01	1991-04-30	California Biotechnology Inc.	Composition and method for administration of pharmaceutically active substances
DK0458894T3 (da)	1989-02-17	1996-10-07	Liposome Co Inc	Lipidexcipiens til nasal afgivelse og topisk påføring
IT8920486A0 (it)	1989-05-12	1989-05-12	Isf Spa	Composizioni farmaceutiche.
US5176132A (en)	1989-05-31	1993-01-05	Fisons Plc	Medicament inhalation device and formulation
JP2642486B2 (ja) *	1989-08-04	1997-08-20	田辺製薬株式会社	難溶性薬物の超微粒子化法
US5258185A (en) *	1989-08-23	1993-11-02	Bauer Kurt H	Highly active, rapidly absorbable formulations of glibenclamide, processes for the production thereof and their use
GB8921222D0 (en)	1989-09-20	1989-11-08	Riker Laboratories Inc	Medicinal aerosol formulations
US5707644A (en)	1989-11-04	1998-01-13	Danbiosyst Uk Limited	Small particle compositions for intranasal drug delivery
GB9001635D0 (en)	1990-01-24	1990-03-21	Ganderton David	Aerosol carriers
US5376386A (en)	1990-01-24	1994-12-27	British Technology Group Limited	Aerosol carriers
US5118494A (en)	1990-03-23	1992-06-02	Minnesota Mining And Manufacturing Company	Use of soluble fluorosurfactants for the preparation of metered-dose aerosol formulations
JPH05963A (ja) *	1990-04-13	1993-01-08	Toray Ind Inc	ポリペプチド類組成物
US5192548A (en)	1990-04-30	1993-03-09	Riker Laboratoires, Inc.	Device
WO1991016882A1 (en)	1990-05-08	1991-11-14	Liposome Technology, Inc.	Direct spray-dried drug/lipid powder composition
WO1991016929A1 (en)	1990-05-10	1991-11-14	Novo Nordisk A/S	A pharmaceutical preparation containing n-glycofurols and n-ethylene glycols
JPH0441421A (ja)	1990-06-07	1992-02-12	Taisho Pharmaceut Co Ltd	肺吸収組成物
JPH04149126A (ja)	1990-10-09	1992-05-22	Mitsubishi Kasei Corp	経粘膜投与用医薬組成物
IL99699A (en)	1990-10-10	2002-04-21	Autoimmune Inc	Drug with the option of oral, intra-intestinal, or inhaled dosing for suppression of autoimmune response associated with type I diabetes
GB9024365D0 (en)	1990-11-09	1991-01-02	Glaxo Group Ltd	Medicaments
JP3507486B2 (ja)	1991-03-15	2004-03-15	アムジエン・インコーポレーテツド	顆粒球コロニー刺激因子の肺内投与
US5320094A (en)	1992-01-10	1994-06-14	The Johns Hopkins University	Method of administering insulin
JPH07503154A (ja) *	1992-01-21	1995-04-06	エス・アール・アイ・インターナシヨナル	微細化ポリペプチド薬剤の改良調製方法
US5482706A (en) *	1992-04-17	1996-01-09	Takeda Chemical Industries, Ltd.	Transmucosal therapeutic composition
CA2115065C (en)	1992-06-12	2000-10-03	Kiyoyuki Sakon	Ultrafine particle powder for inhalation and method for production thereof
US5376359A (en) *	1992-07-07	1994-12-27	Glaxo, Inc.	Method of stabilizing aerosol formulations
DE69332105T2 (de) *	1992-09-29	2003-03-06	Inhale Therapeutic Systems, San Carlos	Pulmonale abgabe von aktiven fragmenten des parathormons
US5364838A (en)	1993-01-29	1994-11-15	Miris Medical Corporation	Method of administration of insulin
JPH08509465A (ja) *	1993-01-29	1996-10-08	マイリスメディカルコーポレーション	ホルモンの肺内送達
BE1006873A6 (nl)	1993-03-26	1995-01-10	Merkus Franciscus W H M	Toedieningsformulering voor nasale insuline toediening.
US5437271A (en)	1993-04-06	1995-08-01	Minnesota Mining And Manufacturing Company	Deagglomerators for dry powder inhalers
US5830853A (en) *	1994-06-23	1998-11-03	Astra Aktiebolag	Systemic administration of a therapeutic preparation
TW402506B (en) *	1993-06-24	2000-08-21	Astra Ab	Therapeutic preparation for inhalation
US5506203C1 (en) *	1993-06-24	2001-02-06	Astra Ab	Systemic administration of a therapeutic preparation
US5747445A (en)	1993-06-24	1998-05-05	Astra Aktiebolag	Therapeutic preparation for inhalation
IS1796B (is) *	1993-06-24	2001-12-31	Ab Astra	Fjölpeptíð lyfjablanda til innöndunar sem einnig inniheldur eykjaefnasamband
US5661130A (en)	1993-06-24	1997-08-26	The Uab Research Foundation	Absorption enhancers for drug administration
GB9314614D0 (en)	1993-07-14	1993-08-25	Minnesota Mining & Mfg	Dry powder inhalers
US5514670A (en)	1993-08-13	1996-05-07	Pharmos Corporation	Submicron emulsions for delivery of peptides
US6051256A (en)	1994-03-07	2000-04-18	Inhale Therapeutic Systems	Dispersible macromolecule compositions and methods for their preparation and use
KR100419037B1 (ko) *	1994-03-07	2004-06-12	넥타르 테라퓨틱스	폐를통한인슐린의전달방법및그조성물
US5451569A (en)	1994-04-19	1995-09-19	Hong Kong University Of Science And Technology R & D Corporation Limited	Pulmonary drug delivery system
SE9404468D0 (sv) *	1994-12-22	1994-12-22	Astra Ab	Powder formulations

1994
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1995
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1997
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Publication number	Publication date
SA94150030B1 (ar)	2006-04-04
NO955226L (no)	1996-02-15
PL178403B1 (pl)	2000-04-28
EG20599A (en)	1999-09-30
SK160195A3 (en)	1997-02-05
KR100372673B1 (ko)	2003-05-12
ATE183920T1 (de)	1999-09-15
DE69420412D1 (de)	1999-10-07
GR3031974T3 (en)	2000-03-31
AU7090194A (en)	1995-01-17
PL312205A1 (en)	1996-04-01
IS1768B (is)	2001-05-02
US5658878A (en)	1997-08-19
IL110084A (en)	1999-07-14
MY112098A (en)	2001-04-30
SK283145B6 (sk)	2003-03-04
JP3874789B2 (ja)	2007-01-31
CN1110301C (zh)	2003-06-04
UA49794C2 (uk)	2002-10-15
DE69420412T2 (de)	2000-04-13
DK0706382T3 (da)	2000-03-13
NO313657B1 (no)	2002-11-11
TW402506B (en)	2000-08-21
JPH08512027A (ja)	1996-12-17
WO1995000127A1 (en)	1995-01-05
CN1129904A (zh)	1996-08-28
BR9406907A (pt)	1996-04-02
EP0706382A1 (en)	1996-04-17
NO955226D0 (no)	1995-12-21
JP2006089496A (ja)	2006-04-06
IL110084A0 (en)	1994-10-07
US5518998C1 (en)	2001-02-13
IS4178A (is)	1994-12-25
US6306440B1 (en)	2001-10-23
MX9404761A (es)	1995-01-31
CA2166108A1 (en)	1995-01-05
EE03221B1 (et)	1999-10-15
JP4294635B2 (ja)	2009-07-15
RU2148398C1 (ru)	2000-05-10
US5518998A (en)	1996-05-21
HU228129B1 (en)	2012-12-28
HUT75065A (en)	1997-03-28
CZ287314B6 (en)	2000-10-11
ES2138087T3 (es)	2000-01-01
EP0706382B1 (en)	1999-09-01
HK1009584A1 (en)	1999-06-04
FI956227L (fi)	1995-12-22
CZ342895A3 (en)	1996-05-15
FI956227A0 (fi)	1995-12-22
NZ268137A (en)	1997-10-24
CA2166108C (en)	2008-10-21
HU9503659D0 (en)	1996-02-28
AU692780B2 (en)	1998-06-18

Publication	Publication Date	Title
FI111688B (fi)	2003-09-15	Menetelmä insuliinin terapeuttisen kuivapulverivalmisteen valmistamiseksi
US6846801B1 (en)	2005-01-25	Systemic administration of a therapeutic preparation
US5506203A (en)	1996-04-09	Systemic administration of a therapeutic preparation
US5747445A (en)	1998-05-05	Therapeutic preparation for inhalation
US6165976A (en)	2000-12-26	Therapeutic preparation for inhalation
FI111909B (fi)	2003-10-15	Menetelmä sisäänhengitykseen tarkoitettujen koostumusten valmistamiseksi
DE69631881T2 (de)	2004-08-19	Pulmonale verabreichung von medikamenten in aerosolform
US20010003739A1 (en)	2001-06-14	Systemic administration of a therapeutic preparation
US20010025037A1 (en)	2001-09-27	Systemic administration of a therapeutic preparation
LT3445B (en)	1995-10-25	Therapeutic preparation for inhalation
NZ328475A (en)	2001-04-27	A pharmaceutical composition containing a polypeptide up to 40 kD and an enhancer for systemic delivery by inhalation

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