ZA941308B - Bisacodyl dosage form - Google Patents

Bisacodyl dosage form

Info

Publication number
ZA941308B
ZA941308B ZA941308A ZA941308A ZA941308B ZA 941308 B ZA941308 B ZA 941308B ZA 941308 A ZA941308 A ZA 941308A ZA 941308 A ZA941308 A ZA 941308A ZA 941308 B ZA941308 B ZA 941308B
Authority
ZA
South Africa
Prior art keywords
colon
bisacodyl
dosage form
lumen
small intestine
Prior art date
Application number
ZA941308A
Other languages
English (en)
Inventor
Paula Denise Davis
Douglas Joseph Dobrozsi
Gary Robert Kelm
Kenneth Gary Mandel
Original Assignee
Procter & Gamble
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.)
Filing date
Publication date
Application filed by Procter & Gamble filed Critical Procter & Gamble
Publication of ZA941308B publication Critical patent/ZA941308B/xx

Links

Classifications

    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • 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
    • 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
    • A61K9/146—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 macromolecular compounds
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4891—Coated capsules; Multilayered drug free capsule shells
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Nanotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medical Informatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Epoxy Compounds (AREA)
ZA941308A 1993-02-26 1994-02-25 Bisacodyl dosage form ZA941308B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US2341293A 1993-02-26 1993-02-26

Publications (1)

Publication Number Publication Date
ZA941308B true ZA941308B (en) 1994-09-30

Family

ID=21814950

Family Applications (1)

Application Number Title Priority Date Filing Date
ZA941308A ZA941308B (en) 1993-02-26 1994-02-25 Bisacodyl dosage form

Country Status (20)

Country Link
US (1) US5670158A (cs)
EP (1) EP0686034B1 (cs)
JP (1) JP3725539B2 (cs)
CN (1) CN1047075C (cs)
AT (1) ATE201991T1 (cs)
AU (1) AU6251094A (cs)
BR (1) BR9405836A (cs)
CA (1) CA2156726C (cs)
CZ (1) CZ286051B6 (cs)
DE (1) DE69427466T2 (cs)
DK (1) DK0686034T3 (cs)
ES (1) ES2157253T3 (cs)
GR (1) GR3036042T3 (cs)
HU (1) HUT72975A (cs)
IL (1) IL108705A (cs)
PL (1) PL176846B1 (cs)
PT (1) PT686034E (cs)
SK (1) SK104895A3 (cs)
WO (1) WO1994018973A1 (cs)
ZA (1) ZA941308B (cs)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5843479A (en) * 1993-02-26 1998-12-01 The Procter & Gamble Company Bisacodyl dosage form with multiple enteric polymer coatings for colonic delivery
US5914132A (en) * 1993-02-26 1999-06-22 The Procter & Gamble Company Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery
US5651983A (en) * 1993-02-26 1997-07-29 The Procter & Gamble Company Bisacodyl dosage form for colonic delivery
US5656290A (en) * 1993-02-26 1997-08-12 The Procter & Gamble Company Bisacodyl dosage form with multiple enteric polymer coatings for colonic delivery
US6028190A (en) 1994-02-01 2000-02-22 The Regents Of The University Of California Probes labeled with energy transfer coupled dyes
GB9412394D0 (en) 1994-06-21 1994-08-10 Danbiosyst Uk Colonic drug delivery composition
US6166024A (en) * 1995-03-30 2000-12-26 Mayo Foundation For Medical Education And Research Use of topical azathioprine and thioguanine to treat colorectal adenomas
KR20000053327A (ko) * 1996-11-15 2000-08-25 데이비드 엠 모이어 결장내 운반에 사용되는 약학적 제형
AR017512A1 (es) * 1997-08-22 2001-09-12 Smithkline Beecham Corp Tabletas de metilcelulosa rapidamente desintegrables para administracion por via oral y procedimiento para prepararlas
IT1296980B1 (it) * 1997-12-17 1999-08-03 Istituto Pirri S R L Capsula doppia come forma farmaceutica per la somministrazione di principi attivi in terapie multiple
DE19913606A1 (de) * 1999-03-25 2000-09-28 Basf Ag Pulverförmige Solubilisationshilfsstoffe für feste pharmazeutische Darreichungsformen
ES2688273T3 (es) * 1999-03-31 2018-10-31 Janssen Pharmaceutica Nv Almidón pregelatinizado en una formulación de liberación controlada
RU2147878C1 (ru) * 1999-08-12 2000-04-27 Открытое акционерное общество Химико-фармацевтический комбинат "Акрихин" Фармацевтическая композиция, обладающая энтеральным действием
BRPI0210096B1 (pt) * 2001-05-30 2015-06-30 Euro Celtique Sa Composição farmacêutica compreendendo bissacodil e poloxâmero, processo para a preparação de composição farmacêutica na forma de cápsula cheia e uso de poloxâmero e bissacodil
GB0124953D0 (en) * 2001-10-17 2001-12-05 Novartis Ag Organic Compounds
US20160184358A9 (en) * 2002-07-15 2016-06-30 George M. Halow Bowel cleansing composition
US7291324B2 (en) * 2002-10-22 2007-11-06 Braintree Laboratories Inc. Method of bowel cleansing
LT2279729T (lt) * 2003-07-17 2016-10-10 Banner Life Sciences, LLC Kontroliuojamo atpalaidavimo preparatas
EP1731151A4 (en) * 2004-03-10 2013-05-01 Taisho Pharmaceutical Co Ltd SOLID PHARMACEUTICAL PREPARATION WITH A HEAVY WATER-SOLUBLE MEDICAMENT
US20070196322A1 (en) * 2005-12-29 2007-08-23 Braintree Laboratories Inc. Method of preparing the colon for virtual colonoscopy
RU2401106C1 (ru) * 2009-04-09 2010-10-10 Закрытое Акционерное Общество "БИОКОМ" Твердая лекарственная форма, обладающая слабительной активностью, и способ ее получения (варианты)
US8211417B1 (en) 2009-10-31 2012-07-03 Harry Snady Method of bowel cleansing
TR201904884T4 (tr) 2012-07-27 2019-05-21 Redhill Biopharma Ltd Koloni̇k boşaltmada kullanima yöneli̇k formülasyonlar ve formülasyonlarin üreti̇m yöntemleri̇
DE102014017936A1 (de) 2014-12-05 2016-06-09 Tracto-Technik Gmbh & Co. Kg Erdbohrvorrichtung
WO2017048566A1 (en) 2015-09-15 2017-03-23 C.B. Fleet Company, Incorporated Bisacodyl compositions and delivery apparatus
CN109984993A (zh) * 2018-01-03 2019-07-09 药大制药有限公司 一种提升比沙可啶栓质量的处方及制备方法
EP4013401A4 (en) 2019-08-12 2023-07-12 Massachusetts Institute of Technology Articles and methods for administration of therapeutic agents
WO2022219573A2 (en) * 2021-04-15 2022-10-20 Rolling Pastures Pte. Ltd. Microencapsulation wall material, suspension core capsule, edible capsule with electronics, methods and a production system for producing the same

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE818022C (de) * 1950-05-05 1951-10-22 Otto Hellmann Papierkorb zur Aufnahme von Papier und Abfaellen
US2764590A (en) * 1952-03-17 1956-09-25 Thomae Gmbh Dr K Certain 4, 4'-disubstituted-diphenylpyridyl methanes and process
US3927195A (en) * 1974-01-31 1975-12-16 Lilly Industries Ltd Production of capsules
JPS5799521A (en) * 1980-12-11 1982-06-21 Eisai Co Ltd Solid composition containing bisacodyl
JPS59193816A (ja) * 1983-04-19 1984-11-02 Morishita Jintan Kk 腸溶性軟カプセルの製造法
IE58110B1 (en) * 1984-10-30 1993-07-14 Elan Corp Plc Controlled release powder and process for its preparation
GB8613688D0 (en) * 1986-06-05 1986-07-09 Euro Celtique Sa Pharmaceutical composition
JPS6320409A (ja) * 1986-07-15 1988-01-28 Nippon Kokan Kk <Nkk> 取鍋精錬方法
US4810707A (en) * 1987-02-25 1989-03-07 Meditech Pharmaceuticals, Inc. Herpes simplex treatment
JPS63258815A (ja) * 1987-04-16 1988-10-26 Kiyuushin Seiyaku Kk ビサコジル含有固形組成物
JPH0672106B2 (ja) * 1987-04-22 1994-09-14 花王株式会社 緩下剤組成物
US5068110A (en) * 1987-09-29 1991-11-26 Warner-Lambert Company Stabilization of enteric coated dosage form
EP0313845A1 (en) * 1987-09-29 1989-05-03 Warner-Lambert Company Stabilization of enteric coated dosage form
DE3818022C2 (de) * 1988-05-24 1994-04-28 Guenter Stephan Weichgelatinekapsel
GB8903564D0 (en) * 1989-02-16 1989-04-05 Rashid Abdul Drug dispensing device
CA2047738C (en) * 1989-02-16 2000-02-15 Marion Eileen Mcneill Dispensing device
GB9004702D0 (en) * 1990-03-02 1990-04-25 Polysystems Limited Dispensing device

Also Published As

Publication number Publication date
CN1047075C (zh) 1999-12-08
IL108705A0 (en) 1994-05-30
DK0686034T3 (da) 2001-08-27
CA2156726A1 (en) 1994-09-01
BR9405836A (pt) 1996-01-16
PL176846B1 (pl) 1999-08-31
EP0686034A1 (en) 1995-12-13
SK104895A3 (en) 1996-06-05
EP0686034B1 (en) 2001-06-13
HUT72975A (en) 1996-06-28
IL108705A (en) 1998-04-05
GR3036042T3 (en) 2001-09-28
CZ204995A3 (en) 1996-04-17
CA2156726C (en) 2000-10-17
DE69427466T2 (de) 2002-04-25
DE69427466D1 (de) 2001-07-19
JP3725539B2 (ja) 2005-12-14
PL310355A1 (en) 1995-12-11
CN1118571A (zh) 1996-03-13
JPH08509958A (ja) 1996-10-22
US5670158A (en) 1997-09-23
WO1994018973A1 (en) 1994-09-01
PT686034E (pt) 2001-10-30
ATE201991T1 (de) 2001-06-15
AU6251094A (en) 1994-09-14
CZ286051B6 (cs) 1999-12-15
ES2157253T3 (es) 2001-08-16
HU9502492D0 (en) 1995-10-30

Similar Documents

Publication Publication Date Title
GR3036042T3 (en) Bisacodyl dosage form
Quentel et al. Antigen uptake and immune responses after oral vaccination
PL342938A1 (en) Preventives or remedies for inflammatory intestinal diseases containing as the active ingredient il-6 antagonists
EP1374902A4 (en) REMEDIES AGAINST INFLAMMATORY INTESTINAL DISEASES
DE69205971D1 (de) Orale dosierungsform mit verzögerter wirkstoffabgabe für die behandlung von intestinalen krankheiten.
AU2003243545A8 (en) Prevention and/or treatment of inflammatory bowel disease using pyy or agonists thereof
DE69719774D1 (de) Pharmazeutische dosierungsform mit mehrfachen enterischen polymer-überzügenzur abgabe im kolon
HU9202808D0 (en) Improvement of down-regulqtion of autoimmunic diseases by means of oral dosing of autoantigenes
IL118240A (en) Oral coated capsule dosage form of omega-3 polyunsaturated acid for release of the acid in the intestine
DE69520492D1 (de) Flüssige arzneizubereitungen enthaltend schilddrüsenhormone
EP0393747A3 (en) Mebeverine dosage form
ES2149733T1 (es) Composicion farmaceutica oral con liberacion modificada que contiene 5-asa y metodo para el tratamiento de enfermedades intestinales.
NO923397L (no) Avgivelsesanordning
CA2032475A1 (en) Pharmaceutical preparations for oral administration that are adapted to release the drug at appropriate sites in the intestines
Ballou et al. Biliary plutonium excretion in the rat
Jacknowitz et al. Nitrofurantoin polyneuropathy: report of two cases
Gasbarrini et al. New concepts concerning management of Helicobacter pylori infection: 2 years after the Maastricht Consensus Report
CO4130184A1 (es) Forma de dosificacion de bisacodyl
HU9300244D0 (en) Method for producing chemotherapeutical agent of antitumourous effect originated of plants and medical preparatives containing it
GB2100602B (en) Device for delivering biologically active substances to the digestive tract.
BR0016469A (pt) Composição para melhorar a resposta proliferativa durante a adaptação do trato gastrointestinal e uso na sìndrome do intestino delgado
SE9003096D0 (sv) Device for administering a physiologically active substance to the gastro-intestinal tract
Gol'dberg et al. Acute toxicity of carminomycin administered perorally to laboratory animals
MX9804578A (es) Composiciones consistiendo en bismuto o uno o mas antimicrobianos, para la prevencion y el tratamiento de trastornos gastrointestinales.
Okubo et al. Mechanisms of stimulatory effect of neuromedin C on pancreatic exocrine secretion in conscious rats