WO1985005036A1 - Traitement topique du diabete a l'aide d'insuline et d'un agent ameliorant la penetration applique sur la peau et recouvert d'une pastille - Google Patents

Traitement topique du diabete a l'aide d'insuline et d'un agent ameliorant la penetration applique sur la peau et recouvert d'une pastille Download PDF

Info

Publication number
WO1985005036A1
WO1985005036A1 PCT/US1985/000695 US8500695W WO8505036A1 WO 1985005036 A1 WO1985005036 A1 WO 1985005036A1 US 8500695 W US8500695 W US 8500695W WO 8505036 A1 WO8505036 A1 WO 8505036A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
layer
skin
insulin
gel
Prior art date
Application number
PCT/US1985/000695
Other languages
English (en)
Inventor
Collin J. Weber
Michael Kazim
Keith Reemtsma
John F. Nicholson
Original Assignee
The Trustees Of Columbia University In The City Of
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 The Trustees Of Columbia University In The City Of filed Critical The Trustees Of Columbia University In The City Of
Publication of WO1985005036A1 publication Critical patent/WO1985005036A1/fr

Links

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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
    • 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

Definitions

  • Exogenous insulin is the mainstay of therapy for human diabetics.
  • a major disadvantage is the necessity to administer the drug parenterally, e.g., with a needle and syringe.
  • the need for at least daily injections of insulin is an important factor in patient compliance and comfort.
  • Penetrant enhancers other than DMSO are known. [Dugard,
  • the present invention overcomes these difficulties and provides a method for treating diabetes involving topical application of a composition to the surface of the skin or a diabetic subject.
  • a composition which when applied to the surface of the skin of a diabetic subject or patient is useful in the treatment of diabetes, comprises a first layer in contact with the skin surface and a second layer covering the first layer.
  • the first layer includes an effective diabetes-treating amount of insulin, an effective enhancing amount of a penetrant enhancer such as dimethyl sulfoxide or n-decyl-methyl sulf- oxide and a suitable carrier.
  • the second layer comprises a suitable adherent, nonporous patch material such as poly ⁇ ethylene.
  • the first layer is in the form of a gel and includes a suitable gel material such as hydroxymethyl cellulose, hydroxypropylmethyl cellulose or hydroxypropyl cellulose.
  • compositions which when applied to the surface of a diabetic patient's or subject's skin are useful in treating diabetes.
  • such a composition includes a first layer in contact with the skin surface and a second layer covering the first layer.
  • the first layer includes an effective diabetes-treating amount of insulin, an effective enhancing amount of a penetrant enhancer and a suitable carrier.
  • the second layer comprises a suitable adherent, nonporous patch material.
  • the first layer may be formulated directly on the surface of the skin, it is generally preferable to first formulate the ingredients and then apply the formulated ingredients to the skin surface to form the layer.
  • Effective diabetes-treating amounts of insulin may vary from the amounts normally required for subcutaneous or intravenous therapy. However, in the practices of the present invention it is contemplated that the amounts will be similar to those presently employed in the other treat- ment modes since one unit of protamine zinc insulin admin ⁇ istered subcutaneously is an appropriate dose for main ⁇ tenance of relative normoglycemia in diabetic rodents [Andersson, A., Diabetologia __ : 269 (1983)].
  • the form of insulin may also vary and includes regular insulin, NPH, Lente and protamine zinc insulin. It is contemplated that insoluble repository forms of insulin may have longer dura ⁇ tions of action than regular insulin.
  • the penetrant enhancer may be any of a number of agents known to enhance the penetration and increase the absorption of drugs across the skin. Examples include dimethyl sulfoxide, dimethyl acetamide, dimethylformamide and n-decyl-methyl sulfoxide. Additional such agents include propylene gly- col, glycerin, lanolins, alcohols, anionic emulsifiers (e.g. sodium lauryl sulfate) and surfactants (nonionic emulsifiers such as polyoxyethylene fatty alcohol ethers and esters; polyoxyethylene fatty acid esters, e.g.
  • poly ⁇ oxyethylene stearate polyoxyethylene sorbitan fatty acid esters and sorbitan fatty acid esters, e.g. sorbitan mon- ostearate; polyoxyethylene glycol fatty acid esters; polyol fatty acid esters, e.g. glyceryl monostearate; and ethoxy- lated lanolin derivatives.
  • DMSO dimethylacetamide, dimethylformamide and most particularly N-decyl-methyl sulfoxide
  • NDMS N-decyl-methyl sulfoxide
  • N-decyl-methyl sulfoxide is at least 15 times more effective than DMSO in skin penetrance enhancement [McCullough, J.L. et al., J. Invest. Dermatol. 6 ⁇ :103 (1976)], and in a less than 1% solution, applied topically, in amounts less than 1.3 ml per day, is safe and without side effects [Physicians Desk Reference, Medical Economics Company, Oradell, New Jersey- (1983)]. Substitution of NDMS for DMSO or lowering the amount of enhancing agent used is particularly desirable since DMSO has several undesirable, dose-related side ef ⁇ fects. [Harter, J., Annals of the New York Academy of Sciences, Vol. 411, Ed., J.C.
  • DMSO in 50% aqueous solution is FDA approved for instillation in the bladder to treat interstitial cystitis [Stewart, B. et al., J. Urology Ll :36 (1976)]. It i expected that biological effects of DMSO in penetr-anc-, enhancement of insulin transport across the skin, even at concentrations as low as 1-5% will be effective since Whitworth and Stevenson.[J. Pharmaceut. Sci. 6 :48 (1971)]
  • the amount of penetrant enhancer present in the first layer may vary over a wide range, depending upon the specific enhancer beinj used. In general, the amount will not exceed about 50% by volume of the first layer.
  • the first layer also includes a suitable carrier.
  • a suitable carrier is water, e.g., deionized dis ⁇ tilled water.
  • Other carriers include alcohols such as methanol or ethanol or aqueous mixtures thereof.
  • the carrier may be formulated in an emulsion or cream base.
  • Hydrophilic Ointment USP a widely available oil-in-water emulsion.
  • Hydrophilic Petrolatum USP a water- and-oil emulsion (Table 2).
  • the first layer may also include additional materials such as emulsifying agents, suspending agents, preservatives and the like.
  • the first layer is in the form of a gel.
  • Suitable gel materials include hydroxymethyl cel ⁇ lulose, hydroxypropylmethyl cellulose or hydroxypropyl cellulose.
  • the use of a gel permit easier application of the insulin and penetrant enhancer to the diabetic subject's skin. In addition, it permits better control over dosage amounts. Finally, it maintains the components of the firs- layer in contact with a defined area of the subject's ski; prior to application of the adherent, nonporous patch.
  • the amount of gel material employed may vary widely depend ⁇ ing upon the identity of the gel material and the identity and amount of penetrant enhancer and carrier. In general, the amount of gel material will not exceed about 50% by volume of the first layer. In one preferred embodiment cf the invention the gel material and penetrant enhancer eacr comprise about 33% by volume of the first layer.
  • the adherent, nonporous patch material may be any of th ⁇ various such materials known to be useful as a patch.
  • a patch material useful in the practices of this invention is polyethylene. .
  • This invention provides a method of treating diabetes which comprises applying to the surface of a diabetic subject' skin a composition of the type described herein for suitable period of time, such as 1-12 hours, to perm insulin present in the composition to penetrate across ____: skin, enter the bloodstream and effect blood sugar levels,
  • Bovine-porcine regular insulin (Eli Lilly and Company, Indianapolis, Indiana) was topically applied to the skin of streptozotocin-diabetic male BO.BR mice, beneath a poly ⁇ ethylene patch (SteridrapeTM - 3M Company, Minneapolis, Minnesota), which was applied to the torso. Drug-skin contact occurred over approximately 1-2 cm ⁇ of body surface. Body hair was clipped 24-72 hours prior to each experiment. Mice were awake with free access to food and water. Animals were judged diabetic if they had more than three blood glucose values >40Q mg/dl over at least 10 days. Blood glucose was measured by the glucose oxidase technique on tail vein blood (Ames dextrometer) [Jarett, R. et al., Diabetes 3,9:7234 (1970)].
  • dimethyl sulfoxide 33% or 50% (DMSO-Sigma) was mixedwith insulin.
  • DMSO added to 100 units of regular insulin resulted in reductions of blood glucose in 8 of 13 mice.
  • DMSO alone had no effect on blood sugar.
  • NDMS n-decyl-methyl sulfoxide

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Composition de traitement du diabète par application sur la surface de la peau d'un sujet diabétique, comprenant une première couche en contact avec la surface de la peau et une deuxième couche recouvrant la première. La première couche contient une quantité efficace d'insuline pour le traitement du diabète, une quantité efficace d'un agent améliorant la pénétration et un support approprié. La deuxième couche comprend un matériau approprié non poreux adhésif en forme de pastille. Dans un mode préféré de réalisation, la première couche est un gel et comprend une substance de gel appropriée. Cette composition est appliquée sur la surface de la peau d'un sujet diabétique pendant une période de temps suffisante pour permettre à l'insuline présente dans la composition de traverser la peau et déployer une action de traitement du diabète.
PCT/US1985/000695 1984-04-30 1985-04-17 Traitement topique du diabete a l'aide d'insuline et d'un agent ameliorant la penetration applique sur la peau et recouvert d'une pastille WO1985005036A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US60560884A 1984-04-30 1984-04-30
US605,608 1984-04-30

Publications (1)

Publication Number Publication Date
WO1985005036A1 true WO1985005036A1 (fr) 1985-11-21

Family

ID=24424421

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1985/000695 WO1985005036A1 (fr) 1984-04-30 1985-04-17 Traitement topique du diabete a l'aide d'insuline et d'un agent ameliorant la penetration applique sur la peau et recouvert d'une pastille

Country Status (3)

Country Link
EP (1) EP0178321A1 (fr)
AU (1) AU4292585A (fr)
WO (1) WO1985005036A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996011705A1 (fr) * 1994-10-13 1996-04-25 Pharmaderm Research & Development Ltd. Formulations comprenant des proteines ou des polypeptides therapeutiquement actifs
US5820876A (en) * 1986-08-28 1998-10-13 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system
WO1998053847A1 (fr) * 1997-05-29 1998-12-03 Ben Gurion University Of The Negev Research And Development Authority Systeme de transport transdermique
US5858398A (en) * 1994-11-03 1999-01-12 Isomed Inc. Microparticular pharmaceutical compositions
EP1017414A1 (fr) * 1997-06-23 2000-07-12 The Research Foundation Of State University Of New York Procede therapeutique destine a traiter le diabete sucre
US6110488A (en) * 1986-08-28 2000-08-29 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system, its use and production process
US6117448A (en) * 1986-08-28 2000-09-12 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system, its use and production process
US6126963A (en) * 1986-08-28 2000-10-03 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system, its use and production process
US6139868A (en) * 1986-08-28 2000-10-31 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system, its use and production process
USRE37934E1 (en) 1986-08-28 2002-12-10 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system
US6667052B2 (en) * 1997-05-29 2003-12-23 Ben Gurion University Of The Negev Research And Development Authority Transdermal delivery system
WO2005112889A2 (fr) * 2004-05-20 2005-12-01 Recordati Ireland Limited Preparations d'apport transmucosal
US7402571B2 (en) 2000-07-31 2008-07-22 Bar-Ilan University Methods and pharmaceutical compositions for healing wounds
US7638484B2 (en) 2003-08-07 2009-12-29 Healor Ltd. Methods for accelerating wound healing by administration of adipokines
US8093211B2 (en) 2000-07-31 2012-01-10 Bar-Ilan University Methods and pharmaceutical compositions for healing wounds
US8349793B2 (en) 2010-01-11 2013-01-08 Heal0r, Ltd. Method for treatment of inflammatory disease and disorder
US20140205559A1 (en) * 2011-05-11 2014-07-24 Alc Therapeutics, Llc Antifungal compositions for the treatment of skin and nails

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE50502T1 (de) * 1984-06-09 1990-03-15 Hoechst Ag Insulinzubereitungen, verfahren zu deren herstellung und deren verwendung.
AUPN089295A0 (en) * 1995-02-02 1995-03-02 International Diabetes Institute Treatment of diabetic neuropathy

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Published, 05 September 1967 CHEN et al. *
Published, 08 September 1970 MacMILLAN et al *
Published, 10 April 1982, NIHO Electric Ind. KK *
Published, 11 March 1975, LOWEY et al. *
Published, 20 April 1976, SMITH *

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6117448A (en) * 1986-08-28 2000-09-12 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system, its use and production process
USRE37934E1 (en) 1986-08-28 2002-12-10 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system
US5820876A (en) * 1986-08-28 1998-10-13 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system
US6264977B1 (en) 1986-08-28 2001-07-24 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system, its use and production process
US6224900B1 (en) 1986-08-28 2001-05-01 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Sealing bag for a transdermal therapeutic system
US6139868A (en) * 1986-08-28 2000-10-31 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system, its use and production process
US6126963A (en) * 1986-08-28 2000-10-03 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system, its use and production process
US6110488A (en) * 1986-08-28 2000-08-29 Lts Lohmann Therapie-Systeme Gmbh & Co. Kg Transdermal therapeutic system, its use and production process
WO1996011705A1 (fr) * 1994-10-13 1996-04-25 Pharmaderm Research & Development Ltd. Formulations comprenant des proteines ou des polypeptides therapeutiquement actifs
AU716868B2 (en) * 1994-10-13 2000-03-09 Pharmaderm Research & Development Ltd. Formulations comprising therapeutically-active proteins or polypeptides
US5707641A (en) * 1994-10-13 1998-01-13 Pharmaderm Research & Development Ltd. Formulations comprising therapeutically-active proteins or polypeptides
US5858398A (en) * 1994-11-03 1999-01-12 Isomed Inc. Microparticular pharmaceutical compositions
US6667052B2 (en) * 1997-05-29 2003-12-23 Ben Gurion University Of The Negev Research And Development Authority Transdermal delivery system
WO1998053847A1 (fr) * 1997-05-29 1998-12-03 Ben Gurion University Of The Negev Research And Development Authority Systeme de transport transdermique
US6274166B1 (en) * 1997-05-29 2001-08-14 Ben Gurion University Of The Negev Research And Development Authority Transdermal delivery system
EP1017414A1 (fr) * 1997-06-23 2000-07-12 The Research Foundation Of State University Of New York Procede therapeutique destine a traiter le diabete sucre
EP1017414A4 (fr) * 1997-06-23 2004-10-06 Res Foundation Ofstate Univers Procede therapeutique destine a traiter le diabete sucre
US7402571B2 (en) 2000-07-31 2008-07-22 Bar-Ilan University Methods and pharmaceutical compositions for healing wounds
US8093211B2 (en) 2000-07-31 2012-01-10 Bar-Ilan University Methods and pharmaceutical compositions for healing wounds
US7638484B2 (en) 2003-08-07 2009-12-29 Healor Ltd. Methods for accelerating wound healing by administration of adipokines
WO2005112889A2 (fr) * 2004-05-20 2005-12-01 Recordati Ireland Limited Preparations d'apport transmucosal
WO2005112889A3 (fr) * 2004-05-20 2006-08-03 Recordati Ireland Ltd Preparations d'apport transmucosal
US8349793B2 (en) 2010-01-11 2013-01-08 Heal0r, Ltd. Method for treatment of inflammatory disease and disorder
US20140205559A1 (en) * 2011-05-11 2014-07-24 Alc Therapeutics, Llc Antifungal compositions for the treatment of skin and nails
US9408867B2 (en) * 2011-05-11 2016-08-09 Veloce Biopharma, Llc Antifungal compositions for the treatment of skin and nails

Also Published As

Publication number Publication date
AU4292585A (en) 1985-11-28
EP0178321A1 (fr) 1986-04-23

Similar Documents

Publication Publication Date Title
WO1985005036A1 (fr) Traitement topique du diabete a l'aide d'insuline et d'un agent ameliorant la penetration applique sur la peau et recouvert d'une pastille
Gajraj et al. Eutectic mixture of local anesthetics (EMLA®) cream
US6274166B1 (en) Transdermal delivery system
KR101706549B1 (ko) 히알루로니다제를 포함하는 국소지방 제거용 주사제 조성물
US4725609A (en) Method of promoting healing
US5145679A (en) Topical emollient for prevention and treatment of circulatory induced lesions
IE59827B1 (en) Antibacterial cream
JPS61186317A (ja) 経皮吸収製剤組成物
US4782049A (en) Tin protoporphyrin and tin mesoporphyrin in the treatment of psoriasis
EP0462075B1 (fr) Utilisation de l'uridine pour le traitement pharmacologique des complications périphériques du diabète
KR102165993B1 (ko) 국소 지방 제거용 주사제 조성물
JPH01287041A (ja) 徐放性製剤
Pătraşcu et al. Ulcerated necrobiosis lipoidica to a teenager with diabetes mellitus and obesity
JPH01503146A (ja) 身体組織の治療方法および身体組織への医薬の投与方法
DE68911132T2 (de) Hematopoietische kolonien stimulierende faktoren zur verbesserung des lipoprotein/cholesterin-profils.
US5200396A (en) Method of treating neurodegenerative disorders using epidermal growth factor
US5006510A (en) Method for relieving chronic pain with a somatostatin analog composition
EP2076243B1 (fr) Formulation liquide du g-csf
ZA200500710B (en) A platform for transdermal formulations (PTF).
US6667052B2 (en) Transdermal delivery system
KR102517928B1 (ko) 히알루로니다제 및 콜린알포세레이트를 포함하는 국소 지방 제거용 주사제 조성물
HU223205B1 (hu) Helyileg alkalmazható készítmény peptidszerű gyógyhatású vegyületek élő szervezetbe vitelére
WO1993010795A1 (fr) Emollient topique destine a la prevention et au traitement de lesions induites par des troubles de la circulation
JPS60174726A (ja) 注射用医薬組成物
CN115364097B (zh) 一种含杂原子环丁烷取代基的吡啶酮衍生物的应用

Legal Events

Date Code Title Description
AK Designated states

Designated state(s): AU DK JP

AL Designated countries for regional patents

Designated state(s): AT BE CH DE FR GB IT LU NL SE