Guide to the Syntex Collection of Pharmaceutical Advertising
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(12) Patent Application Publication (10) Pub. No.: US 2008/0317805 A1 Mckay Et Al
US 20080317805A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0317805 A1 McKay et al. (43) Pub. Date: Dec. 25, 2008 (54) LOCALLY ADMINISTRATED LOW DOSES Publication Classification OF CORTICOSTEROIDS (51) Int. Cl. A6II 3/566 (2006.01) (76) Inventors: William F. McKay, Memphis, TN A6II 3/56 (2006.01) (US); John Myers Zanella, A6IR 9/00 (2006.01) Cordova, TN (US); Christopher M. A6IP 25/04 (2006.01) Hobot, Tonka Bay, MN (US) (52) U.S. Cl. .......... 424/422:514/169; 514/179; 514/180 (57) ABSTRACT Correspondence Address: This invention provides for using a locally delivered low dose Medtronic Spinal and Biologics of a corticosteroid to treat pain caused by any inflammatory Attn: Noreen Johnson - IP Legal Department disease including sciatica, herniated disc, Stenosis, mylopa 2600 Sofamor Danek Drive thy, low back pain, facet pain, osteoarthritis, rheumatoid Memphis, TN38132 (US) arthritis, osteolysis, tendonitis, carpal tunnel syndrome, or tarsal tunnel syndrome. More specifically, a locally delivered low dose of a corticosteroid can be released into the epidural (21) Appl. No.: 11/765,040 space, perineural space, or the foramenal space at or near the site of a patient's pain by a drug pump or a biodegradable drug (22) Filed: Jun. 19, 2007 depot. E Day 7 8 Day 14 El Day 21 3OO 2OO OO OO Control Dexamethasone DexamethasOne Dexamethasone Fuocinolone Fluocinolone Fuocinolone 2.0 ng/hr 1Ong/hr 50 ng/hr 0.0032ng/hr 0.016 ng/hr 0.08 ng/hr Patent Application Publication Dec. 25, 2008 Sheet 1 of 2 US 2008/0317805 A1 900 ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 80.0 - 7OO – 6OO - 5OO - E Day 7 EDay 14 40.0 - : El Day 21 2OO - OO = OO – Dexamethasone Dexamethasone Dexamethasone Fuocinolone Fluocinolone Fuocinolone 2.0 ng/hr 1Ong/hr 50 ng/hr O.OO32ng/hr O.016 ng/hr 0.08 nghr Patent Application Publication Dec. -
Nitrate Prodrugs Able to Release Nitric Oxide in a Controlled and Selective
Europäisches Patentamt *EP001336602A1* (19) European Patent Office Office européen des brevets (11) EP 1 336 602 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.7: C07C 205/00, A61K 31/00 20.08.2003 Bulletin 2003/34 (21) Application number: 02425075.5 (22) Date of filing: 13.02.2002 (84) Designated Contracting States: (71) Applicant: Scaramuzzino, Giovanni AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU 20052 Monza (Milano) (IT) MC NL PT SE TR Designated Extension States: (72) Inventor: Scaramuzzino, Giovanni AL LT LV MK RO SI 20052 Monza (Milano) (IT) (54) Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases (57) New pharmaceutical compounds of general effects and for this reason they are useful for the prep- formula (I): F-(X)q where q is an integer from 1 to 5, pref- aration of medicines for prevention and treatment of in- erably 1; -F is chosen among drugs described in the text, flammatory, ischemic, degenerative and proliferative -X is chosen among 4 groups -M, -T, -V and -Y as de- diseases of musculoskeletal, tegumental, respiratory, scribed in the text. gastrointestinal, genito-urinary and central nervous sys- The compounds of general formula (I) are nitrate tems. prodrugs which can release nitric oxide in vivo in a con- trolled and selective way and without hypotensive side EP 1 336 602 A1 Printed by Jouve, 75001 PARIS (FR) EP 1 336 602 A1 Description [0001] The present invention relates to new nitrate prodrugs which can release nitric oxide in vivo in a controlled and selective way and without the side effects typical of nitrate vasodilators drugs. -
(CD-P-PH/PHO) Report Classification/Justifica
COMMITTEE OF EXPERTS ON THE CLASSIFICATION OF MEDICINES AS REGARDS THEIR SUPPLY (CD-P-PH/PHO) Report classification/justification of medicines belonging to the ATC group D07A (Corticosteroids, Plain) Table of Contents Page INTRODUCTION 4 DISCLAIMER 6 GLOSSARY OF TERMS USED IN THIS DOCUMENT 7 ACTIVE SUBSTANCES Methylprednisolone (ATC: D07AA01) 8 Hydrocortisone (ATC: D07AA02) 9 Prednisolone (ATC: D07AA03) 11 Clobetasone (ATC: D07AB01) 13 Hydrocortisone butyrate (ATC: D07AB02) 16 Flumetasone (ATC: D07AB03) 18 Fluocortin (ATC: D07AB04) 21 Fluperolone (ATC: D07AB05) 22 Fluorometholone (ATC: D07AB06) 23 Fluprednidene (ATC: D07AB07) 24 Desonide (ATC: D07AB08) 25 Triamcinolone (ATC: D07AB09) 27 Alclometasone (ATC: D07AB10) 29 Hydrocortisone buteprate (ATC: D07AB11) 31 Dexamethasone (ATC: D07AB19) 32 Clocortolone (ATC: D07AB21) 34 Combinations of Corticosteroids (ATC: D07AB30) 35 Betamethasone (ATC: D07AC01) 36 Fluclorolone (ATC: D07AC02) 39 Desoximetasone (ATC: D07AC03) 40 Fluocinolone Acetonide (ATC: D07AC04) 43 Fluocortolone (ATC: D07AC05) 46 2 Diflucortolone (ATC: D07AC06) 47 Fludroxycortide (ATC: D07AC07) 50 Fluocinonide (ATC: D07AC08) 51 Budesonide (ATC: D07AC09) 54 Diflorasone (ATC: D07AC10) 55 Amcinonide (ATC: D07AC11) 56 Halometasone (ATC: D07AC12) 57 Mometasone (ATC: D07AC13) 58 Methylprednisolone Aceponate (ATC: D07AC14) 62 Beclometasone (ATC: D07AC15) 65 Hydrocortisone Aceponate (ATC: D07AC16) 68 Fluticasone (ATC: D07AC17) 69 Prednicarbate (ATC: D07AC18) 73 Difluprednate (ATC: D07AC19) 76 Ulobetasol (ATC: D07AC21) 77 Clobetasol (ATC: D07AD01) 78 Halcinonide (ATC: D07AD02) 81 LIST OF AUTHORS 82 3 INTRODUCTION The availability of medicines with or without a medical prescription has implications on patient safety, accessibility of medicines to patients and responsible management of healthcare expenditure. The decision on prescription status and related supply conditions is a core competency of national health authorities. -
United States Patent (10) Patent No.: US 7,524,836 B2 Del Soldato (45) Date of Patent: Apr
USOO7524836B2 (12) United States Patent (10) Patent No.: US 7,524,836 B2 Del Soldato (45) Date of Patent: Apr. 28, 2009 (54) NITROOXYDERIVATIVESTEROIDAL JP 58-045724 3, 1983 COMPOUNDS JP 5-39.261 2, 1992 JP 4-273892 9, 1992 (75) Inventor: Piero Del Soldato, Milan (IT) WO 98.15568 4f1998 OTHER PUBLICATIONS (73) Assignee: Nicox S.A., Paris (FR) English language abstract of JP 58-045724. (*) Notice: Subject to any disclaimer, the term of this English language abstract of JP4-273892. patent is extended or adjusted under 35 English language abstract of DE 19634793. U.S.C. 154(b) by 173 days. K. B. Schwarz, “Oxidative Sress During Viral Infection: A Review”. Free Radical Biology & Medicine, vol. 21, No. 5, 1996, pp. 641-649. Goodman & Gillman, “The Pharmacological Basis of Therapeutics'. (21) Appl. No.: 11/643,887 9" Edition, 1996, McGraw-Hill Health preffsions Division, pp. 1-1. 1459–1465 and 1474. (22) Filed: Dec. 22, 2006 Martindale, The Extraphamacopeia,30" Edition, 1993, pp. 712-723. O O Nenseter et al., “Paracetamol inhibits Copper Ion-Induced, AZO Com (65) Prior Publication Data pound-Initialed, and Mononuclear Cell-Mediated Oxidative Modifi US 2007/O142342 A1 June 21, 2007 cation of LDL', Arterioscierosis, Thombosis, and Vascular Biology, s vol. 15, No. 9, Sep. 1995, pp. 1338-1344. O O Baylis et al. “Chronic Blockade of Nitric Oxide Synthesis in the Rat Related U.S. Application Data Produces Syntemic Hypertension and Glomemerular Damage'. J. (62) Division of application No. 1 1/028, 198, filed on Jan. 4, Clin. Investigation, vol.90, 1992, pp. -
)&F1y3x PHARMACEUTICAL APPENDIX to THE
)&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE -
A New Robust Technique for Testing of Glucocorticosteroids in Dogs and Horses Terry E
Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2007 A new robust technique for testing of glucocorticosteroids in dogs and horses Terry E. Webster Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Veterinary Toxicology and Pharmacology Commons Recommended Citation Webster, Terry E., "A new robust technique for testing of glucocorticosteroids in dogs and horses" (2007). Retrospective Theses and Dissertations. 15029. https://lib.dr.iastate.edu/rtd/15029 This Thesis is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. A new robust technique for testing of glucocorticosteroids in dogs and horses by Terry E. Webster A thesis submitted to the graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Major: Toxicology Program o f Study Committee: Walter G. Hyde, Major Professor Steve Ensley Thomas Isenhart Iowa State University Ames, Iowa 2007 Copyright © Terry Edward Webster, 2007. All rights reserved UMI Number: 1446027 Copyright 2007 by Webster, Terry E. All rights reserved. UMI Microform 1446027 Copyright 2007 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, MI 48106-1346 ii DEDICATION I want to dedicate this project to my wife, Jackie, and my children, Shauna, Luke and Jake for their patience and understanding without which this project would not have been possible. -
Steroid Use in Prednisone Allergy Abby Shuck, Pharmd Candidate
Steroid Use in Prednisone Allergy Abby Shuck, PharmD candidate 2015 University of Findlay If a patient has an allergy to prednisone and methylprednisolone, what (if any) other corticosteroid can the patient use to avoid an allergic reaction? Corticosteroids very rarely cause allergic reactions in patients that receive them. Since corticosteroids are typically used to treat severe allergic reactions and anaphylaxis, it seems unlikely that these drugs could actually induce an allergic reaction of their own. However, between 0.5-5% of people have reported any sort of reaction to a corticosteroid that they have received.1 Corticosteroids can cause anything from minor skin irritations to full blown anaphylactic shock. Worsening of allergic symptoms during corticosteroid treatment may not always mean that the patient has failed treatment, although it may appear to be so.2,3 There are essentially four classes of corticosteroids: Class A, hydrocortisone-type, Class B, triamcinolone acetonide type, Class C, betamethasone type, and Class D, hydrocortisone-17-butyrate and clobetasone-17-butyrate type. Major* corticosteroids in Class A include cortisone, hydrocortisone, methylprednisolone, prednisolone, and prednisone. Major* corticosteroids in Class B include budesonide, fluocinolone, and triamcinolone. Major* corticosteroids in Class C include beclomethasone and dexamethasone. Finally, major* corticosteroids in Class D include betamethasone, fluticasone, and mometasone.4,5 Class D was later subdivided into Class D1 and D2 depending on the presence or 5,6 absence of a C16 methyl substitution and/or halogenation on C9 of the steroid B-ring. It is often hard to determine what exactly a patient is allergic to if they experience a reaction to a corticosteroid. -
Etats Rapides
List of European Pharmacopoeia Reference Standards Effective from 2015/12/24 Order Reference Standard Batch n° Quantity Sale Information Monograph Leaflet Storage Price Code per vial Unit Y0001756 Exemestane for system suitability 1 10 mg 1 2766 Yes +5°C ± 3°C 79 ! Y0001561 Abacavir sulfate 1 20 mg 1 2589 Yes +5°C ± 3°C 79 ! Y0001552 Abacavir for peak identification 1 10 mg 1 2589 Yes +5°C ± 3°C 79 ! Y0001551 Abacavir for system suitability 1 10 mg 1 2589 Yes +5°C ± 3°C 79 ! Y0000055 Acamprosate calcium - reference spectrum 1 n/a 1 1585 79 ! Y0000116 Acamprosate impurity A 1 50 mg 1 3-aminopropane-1-sulphonic acid 1585 Yes +5°C ± 3°C 79 ! Y0000500 Acarbose 3 100 mg 1 See leaflet ; Batch 2 is valid until 31 August 2015 2089 Yes +5°C ± 3°C 79 ! Y0000354 Acarbose for identification 1 10 mg 1 2089 Yes +5°C ± 3°C 79 ! Y0000427 Acarbose for peak identification 3 20 mg 1 Batch 2 is valid until 31 January 2015 2089 Yes +5°C ± 3°C 79 ! A0040000 Acebutolol hydrochloride 1 50 mg 1 0871 Yes +5°C ± 3°C 79 ! Y0000359 Acebutolol impurity B 2 10 mg 1 -[3-acetyl-4-[(2RS)-2-hydroxy-3-[(1-methylethyl)amino] propoxy]phenyl] 0871 Yes +5°C ± 3°C 79 ! acetamide (diacetolol) Y0000127 Acebutolol impurity C 1 20 mg 1 N-(3-acetyl-4-hydroxyphenyl)butanamide 0871 Yes +5°C ± 3°C 79 ! Y0000128 Acebutolol impurity I 2 0.004 mg 1 N-[3-acetyl-4-[(2RS)-3-(ethylamino)-2-hydroxypropoxy]phenyl] 0871 Yes +5°C ± 3°C 79 ! butanamide Y0000056 Aceclofenac - reference spectrum 1 n/a 1 1281 79 ! Y0000085 Aceclofenac impurity F 2 15 mg 1 benzyl[[[2-[(2,6-dichlorophenyl)amino]phenyl]acetyl]oxy]acetate -
Fluocinolone Acetonide Promotes the Proliferation and Mineralization Of
Basic Research—Biology Fluocinolone Acetonide Promotes the Proliferation and Mineralization of Dental Pulp Cells Zhongning Liu, DDS, MS,* Ting Jiang, DDS, PhD,* Yixiang Wang, DDS, MS,† and Xinzhi Wang, DDS, PhD* Abstract Introduction: The aim of this study was to investigate Key Words the role of the steroid fluocinolone acetonide on the Dental pulp cells, fluocinolone acetonide, mineralization, proliferation proliferation and mineralization of human dental pulp cells (DPCs). The potential effect of fluocinolone aceto- he recovery of injured dental pulp is still one of the unresolved clinical problems. nide on reparative dentin formation and the recovery TWhen unexpected pulp exploration occurs, the survival of vital pulp will be more of injured dental pulp were evaluated. Methods: The difficult. Because healthy and vital pulp can promise a better prognosis of the injured proliferative effect of fluocinolone acetonide on DPCs tooth, preserving the vitality of pulp tissue is of key importance for long-time tooth pres- was analyzed by cholecystokinin octapeptide assay ervation (1). The ideal dental pulp capping agent should not only induce the formation and flow cytometry. The mineralized effect of fluocino- of reparative dentin but also inhibit inflammatory processes. The widely used capping lone acetonide was investigated by the detection of agents (ie, calcium hydroxide and mineral trioxide aggregate) are mainly focused on mineralization-related biomarkers including alkaline the closure of the exposed pulp; however, they are short of the anti-inflammation effect. phosphatase (ALP), bone sialoprotein, and osteocalcin So far, there is no ideal dental pulp capping material for the repair of slightly inflam- by using ALP histochemical staining, ALP activity, immu- matory pulp cases. -
Partial Agreement in the Social and Public Health Field
COUNCIL OF EUROPE COMMITTEE OF MINISTERS (PARTIAL AGREEMENT IN THE SOCIAL AND PUBLIC HEALTH FIELD) RESOLUTION AP (88) 2 ON THE CLASSIFICATION OF MEDICINES WHICH ARE OBTAINABLE ONLY ON MEDICAL PRESCRIPTION (Adopted by the Committee of Ministers on 22 September 1988 at the 419th meeting of the Ministers' Deputies, and superseding Resolution AP (82) 2) AND APPENDIX I Alphabetical list of medicines adopted by the Public Health Committee (Partial Agreement) updated to 1 July 1988 APPENDIX II Pharmaco-therapeutic classification of medicines appearing in the alphabetical list in Appendix I updated to 1 July 1988 RESOLUTION AP (88) 2 ON THE CLASSIFICATION OF MEDICINES WHICH ARE OBTAINABLE ONLY ON MEDICAL PRESCRIPTION (superseding Resolution AP (82) 2) (Adopted by the Committee of Ministers on 22 September 1988 at the 419th meeting of the Ministers' Deputies) The Representatives on the Committee of Ministers of Belgium, France, the Federal Republic of Germany, Italy, Luxembourg, the Netherlands and the United Kingdom of Great Britain and Northern Ireland, these states being parties to the Partial Agreement in the social and public health field, and the Representatives of Austria, Denmark, Ireland, Spain and Switzerland, states which have participated in the public health activities carried out within the above-mentioned Partial Agreement since 1 October 1974, 2 April 1968, 23 September 1969, 21 April 1988 and 5 May 1964, respectively, Considering that the aim of the Council of Europe is to achieve greater unity between its members and that this -
Ep 0173478 A1
Patentamt JEuropaischesJ European Patent Office @ Publication number: 0173 478 ^ ^ Office europeen des brevets EUROPEAN PATENT APPLICATION Application number: 85305552.3 © 'nt. CI ": A 61 K 35/78, A 61 K 31 /57 Dateof filing: 05.08.85 (A61K35/78, 31 :57),(A61K31/57, 31 :23, 31 :20) @ Priority: 15.08.84 GB 8420771 @ Applicant: EFAMOL LIMITED, Efamol House Woodbridge Meadows, Guildford Surrey GU1 1BA (GB) @ Date of publication of application: 05.03.86 @ Bulletin 86/10 efamol House woodbridge meadows, Guildford Surrey GU1 1BA (GB) @ Representative : Caro, William Egerton et al, J. MILLER & @ Designated Contracting States: AT BE CH DE FR GB IT CO. Lincoln House 296-302 High Holborn, London LILUNLSE WC1V7JH(GB) @ Treatment of skin disorders. A topical composition for skin treatment contains an anti- inflammatory glucocorticoid in combination with an essential fatty acid (EFA) of the n-6 or n-3 series or equivalent poly- unsaturated fatty acid, as such or in the form of a physio- logically acceptable derivative convertible in the body thereto. FIELD OF INVENTION The invention relates to compositions of y-linolenic acid and related materials with anti-inflammatory glucocorticoids and to the treatment of inflammatory skin disorders with them. BACKGROUND AND EXPLANATION OF INVENTION Much interest has been shown in recent years in essential fatty acid metabolism, especially in its relation to prosta- glandin (PG) metabolism and in particular to the balance of 1-series and 2-series PGs in the body. The main dietary essential fatty acid (EFA) utilised in the fully healthy human body is linoleic acid, but the Δ6- desaturase that converts it to the next acid in the n-6 series, namely y-linoleic acid (GLA) is at a low level of activity in many conditions. -
Aspects of the Bioavailability of Topical Corticosteroid
- - ASPECTS OF THE BIOAVAILABILITY OF TOPICAL CORTICOSTEROID FORMULATIONS. A Thesis Submitted to RHOD ES UNIVERSITY in Partial Fulfilment of the Requirements for the Degree of MASTER OF SCIENCE by ASHLEY DENIS MAGNUS B.Pharm.(Rhodes) School of Pharmaceutical Sciences, Rhodes University, Grahamstown, South Africa. 6140 November 1978. - i - CONTENTS ABSTRACT iii ACKNOWLEDGEMENTS iv PREPARATIONS v STANDARDS vi INSTRUMENTA TION vii STRUCTURES viii 1. INTRODUCTION 1 1.1 BIOASSAYS USED TO ASSESS TOPICAL STEROID ACTIVITY 1 1. 2 TEE HUMAN VASOCONSTRICTOR ASSAY AS A MEASURE OF TOPICAL STEROID ACTIVITY 5 1 .2.1 Alcoholic Vasoconstrictor Studies 5 1.2.2 Studies of Vasoconstriction in Other Solvents 9 1.2.3 Studied of Vasoconstri ction in Formulated Products 10 1. 3 THE MECHANISM OF BLANCHING 1 6 1.4 THE SKIN AS A CORTICOSTEROID RESERVOIR 18 1. 5 TEE CORRELATION OF VASOCONSTRICTOR ACTIVITY WITE CLINICAL EFFICACY 19 1. 6 THE EFFECT OF EXTEMPORANEOUS DILUTION OF TOPICAL CORTICO- STEROID FORMULATIONS 20 1.6.1 Pharmaceutical Considerations 21 1.6.2 Bacteriological Consider ations 22 1.6.3 Biopharmaceutical Considerations 23 2. METHODS 24 2.1 TEE BLANCHING ASSAY 24 2.1 .1 Volunteers 24 2.1 . 2 Mode of Application 24 2 .1.3 Reading of Results 26 2.2 STATISTICAL EVALUATION 27 2 . 3 CALCULATION OF PERCENT TOTAL POSSIBLE SCORE (% TPS) 28 2.4 DETERMINATION OF AREA UNDER THE BLANCHING PROFILE 28 3. DISCUSSION 31 3 .1 TEE ASSESSMENT OF VARIABLES AFFECTING TEE BLANCHING ABILITY OF FORMULATED PRODUCTS 31 - ii - CONTENTS (continued)/ 3.1. 1 The Effect of the Amount of Formulated Product Applied to the Test Site 32 3.