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WO2004000266A1 - Method for oral transmucosal delivery of interferon - Google Patents

Method for oral transmucosal delivery of interferon Download PDF

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Publication number
WO2004000266A1
WO2004000266A1 PCT/RU2002/000300 RU0200300W WO2004000266A1 WO 2004000266 A1 WO2004000266 A1 WO 2004000266A1 RU 0200300 W RU0200300 W RU 0200300W WO 2004000266 A1 WO2004000266 A1 WO 2004000266A1
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Prior art keywords
interferon
mammal
aerosol
oral
alpha
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Application number
PCT/RU2002/000300
Other languages
French (fr)
Inventor
Yuriy Vasilievich Tyagotin
Evgeny Nikolaevich Sventytsky
Igor Anatolievich Pomytkin
Pavel Vasilievich Veteletsky
Original Assignee
Yuriy Vasilievich Tyagotin
Evgeny Nikolaevich Sventytsky
Igor Anatolievich Pomytkin
Pavel Vasilievich Veteletsky
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Publication date
Application filed by Yuriy Vasilievich Tyagotin, Evgeny Nikolaevich Sventytsky, Igor Anatolievich Pomytkin, Pavel Vasilievich Veteletsky filed Critical Yuriy Vasilievich Tyagotin
Priority to AU2002330801A priority Critical patent/AU2002330801A1/en
Priority to PCT/RU2002/000300 priority patent/WO2004000266A1/en
Publication of WO2004000266A1 publication Critical patent/WO2004000266A1/en

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    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A61K38/212—IFN-alpha

Definitions

  • the present invention relates to a method for oral transmucosal delivery of interferon.
  • Interferons are naturally occurring proteins with antiviral, antiproliferative and immunoregulatory activity.
  • the following definition for interferon has been accepted by international committee assembled to devise a system for the orderly nomenclature of interferons: "To qualify as an interferon a factor must be a protein which exerts virus nonspecific, antiviral activity at least in homologous cells through cellular metabolic processes involving synthesis of both RNA and protein.”
  • Four distinct classes of interferons are known to exist in humans. Pestka et al., Ann. Rev. Biochem.. 56: 727 (1987): Emanuel and Pestka, J. Biol. Chem.
  • the three main human interferons are known as IFN-alpha, IFN-beta and IFN-gamma.
  • the IFN-alpha family represents the predominant class of human IFNs.
  • Intramuscular administration is a predominant route of interferon delivery to a systemic circulation of mammals.
  • the present invention provides a method for oral transmucosal delivery of interferon comprising the steps of: (a) providing an interferon formulation comprising a therapeutically effective amount of interferon, (b) administering said interferon formulation in form of aerosol consisting of solid particles or liquid droplets with mass median aerodynamic diameter from 4 to 150 ⁇ m sublingually into a mammal's oral cavity, and (c) delivering said interferon by absorption through a mammal's oral mucosal tissue.
  • a particular advantage of the present invention is that the level of interferon in systemic circulation achieved in a mammal with an amount of interferon when administered into a mammal's oral cavity in form of aerosol is greater than the level achievable with the same amount of interferon administered into a mammal's oral cavity in non-aerosol form and under otherwise equal conditions. Accordingly, it is now possible through the practice of this invention to achieve certain desired therapeutic effects using less amount of interferon than was heretofore possible.
  • the desired therapeutic effects achievable through the practice of this invention include all known in the art therapeutic effects of interferon. Such effects include, but are not limited to, antiviral, antiproliferative, antitumor, antibacterial, and immunoregulatory action of interferon in mammals. Therefore, in practicing this invention, it is possible to minimize potential adverse effects, which may be associated with larger, therapeutic doses of the interferon and still achieve the therapeutic effect.
  • aerosol means a colloidal system consisting of very finely divided solid particles or liquid droplets dispersed in and surrounded by a gas.
  • the present invention is not limited in any way to a specific device for aerosol preparation but is applicable to all such devices now known or subsequently developed.
  • the therapeutically effective amount of interferon is within the skill of those who practice in the art having the benefit of the disclosure herein.
  • interferon will be present in method of the invention in amounts within its normal or less dosage unit and daily regimen ranges as detailed in medical literature.
  • the dosage range will be from about 100 IU to about 5x10 6 IU interferon per mammal.
  • mammals are administered about 3x10 6 IU human recombinant interferon-alpha per mammal per day.
  • the present invention is not limited in any way to specific interferon but is applicable to all such interferon now known or subsequently discovered or developed. Nonetheless, a preferred interferon for use in the method of this invention is human recombinant interferon-alpha.
  • the interferon formulation may be formulated with various pharmaceutically acceptable carriers or diluents in the form of liquid aerosols, solid aerosols, or sprays.
  • Such carriers can include solid diluents, sterile aqueous media, non-toxic organic solvents, and etc.
  • the interferon formulation may be formulated with various pharmaceutical ingredients known from the art. These ingredients may include, but are not limited to, buffering agents (such as phosphate buffer, carbonate buffer, tris buffer, tartrate buffer, borate buffer, acetate buffer, or maleate buffer), colorants, flavorants, coating agents, suspending agents, sweetening agents, anti-fungal preservatives, antimicrobial preservatives, clarifying agents, antioxidants, surfactants, and tonicity agents.
  • buffering agents such as phosphate buffer, carbonate buffer, tris buffer, tartrate buffer, borate buffer, acetate buffer, or maleate buffer
  • colorants such as phosphate buffer, carbonate buffer, tris buffer, tartrate buffer, borate buffer, acetate buffer, or maleate buffer
  • colorants such as phosphate buffer, carbonate buffer, tris buffer, tartrate buffer, borate buffer, acetate buffer, or maleate buffer
  • colorants such as phosphate buffer, carbonate buffer, tris buffer, tartrate buffer, borate buffer,
  • Such absorption promoters may include, but are not limited to, as lecithin, fatty acids, chitosan, salicylates, amino acids, emulsifiers like polyoxyethylene alkyl esters and sodium lauryl sulfate, caproic acid, lactic acid, malic acid, citric acid, pyrrolidonecarboxylic acid, N-alkylpyrrolidones, benzalkonium chloride, cetylpyridinium chloride, cetyltrimethylammonium bromide, cyclodextrins, dextran sulfate, lauric acid, lysophosphatidylcholine, menthol, methoxysalicylate, methyl oleate, polyoxyethylene, polysorbate, sodium glycocholate, sodium glycodeoxycholate, sodium taurocholate, sulfoxides, various alkyl glycosides, etc.
  • the following examples are presented to demonstrate the invention. The examples are illustrative only and
  • This example shows that sublingual administration of interferon in form of aerosol resulted in improved transmucosal delivery of interferon.
  • mice were subdivided into three groups. Mice in the first group (control 1) received sublingually solution of 2.5 ⁇ g (0.5 ⁇ 10 6 IU) rhlFN-alpha dissolved in 0.1 ml of saline (pH 7.2). Mice in the second group (control 2) received intramuscularly 2.5 ⁇ g (0.5x10 6 IU) of rhlFN-alpha dissolved in 0.1 ml of saline (pH 7.2).
  • This example shows that sublingual administration of interferon formulation comprising interferon and an absorption promoter in form of aerosol resulted in improved transmucosal delivery of interferon.
  • mice were subdivided into two groups. Mice in the first group (control) received sublingually solution of 2.5 ⁇ g (0.5 ⁇ l0 6 IU) rhlFN-alpha dissolved in 0.1 ml of saline (pH 7.2) with addition of 0.01 mg soy lecithin as the absorption promoter.
  • mice in the second group received sublingually interferon formulation comprising 2.5 ⁇ g (0.5x10 6 IU) rhlFN-alpha in form of liquid aerosol by the following method: parent solution of 2.5 ⁇ g (0.5x10 6 IU) rhlFN-alpha was prepared by dissolution of 2.5 ⁇ g (0.5x10 6 IU) rhlFN-alpha in 0.1 ml of saline (pH 7.2) with addition of 0.01 mg soy lecithin as the absorption promoter, this solution was sprayed by nebulizer to form liquid aerosol consisting of liquid droplets with mass median aerodynamic diameter from 8 to 150 ⁇ m, and this aerosol was administered to field under tongue in mouse's oral cavity. Absorption of rhlFN-alpha through oral mucosa into systemic circulation was assayed in the course of time with human interferon alpha ELISA.
  • interferon formulation comprising interferon and an absorption promoter in liquid aerosol form
  • improved transmucosal delivery of interferon into systemic circulation which delivery is significantly much greater as compared to administration of the same amounts of interferon and the absorption promoter in liquid sublingual non-aerosol form and under otherwise equal conditions (control).

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

Abstract

The invention relates to a method for oral transmucosal delivery of interferon comprising the steps of: (a) providing an interferon formulation comprising a therapeutically effective amount of interferon, (b) administering said interferon formulation in form of aerosol consisting of solid particles or liquid droplets with mass median aerodynamic diameter from 4 to 150 µm sublingually into a mammal's oral cavity, and (c) delivering said interferon by absorption through a mammal's oral mucosal tissue. A particular advantage of the present invention is that the level of interferon in systemic circulation achieved in a mammal with an amount of interferon when administered into a mammal's oral cavity in form of aerosol is greater than the level achievable with the same amount of interferon administered into a mammal's oral cavity in non-aerosol form and under otherwise equal conditions.

Description

METHOD FOR ORAL TRANSMUCOSAL DELIVERY OF
INTERFERON
FIELD OF THE INVENTION The present invention relates to a method for oral transmucosal delivery of interferon.
BACKGROUND OF THE INVENTION
Interferons (IFNs) are naturally occurring proteins with antiviral, antiproliferative and immunoregulatory activity. The following definition for interferon has been accepted by international committee assembled to devise a system for the orderly nomenclature of interferons: "To qualify as an interferon a factor must be a protein which exerts virus nonspecific, antiviral activity at least in homologous cells through cellular metabolic processes involving synthesis of both RNA and protein." J. Interferon Research. 1: pp. vi (1980). Four distinct classes of interferons are known to exist in humans. Pestka et al., Ann. Rev. Biochem.. 56: 727 (1987): Emanuel and Pestka, J. Biol. Chem. 268: 12565 (1993). The three main human interferons are known as IFN-alpha, IFN-beta and IFN-gamma. The IFN-alpha family represents the predominant class of human IFNs. Intramuscular administration is a predominant route of interferon delivery to a systemic circulation of mammals.
Delivery of drugs through the oral absorptive mucosa is a very attractive and feasible site for systemic delivery of interferons. The major advantages of this route for systemic action of a drug formulation are that it bypass the hepatic first-pass metabolism and avoids pre-systemic elimination in the gastrointestinal tract. Furthermore, the oral cavity is a highly acceptable by patients.
Surprisingly, we have now found that administering interferon into a mammal's oral cavity under tongue in aerosol form manifests much more pronounced raising the blood level of interferon than the same dose of interferon in a non-aerosol form and under otherwise equal conditions.
It is an object of the present invention to provide the improved method for oral transmucosal delivery of interferon. DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a method for oral transmucosal delivery of interferon comprising the steps of: (a) providing an interferon formulation comprising a therapeutically effective amount of interferon, (b) administering said interferon formulation in form of aerosol consisting of solid particles or liquid droplets with mass median aerodynamic diameter from 4 to 150 μm sublingually into a mammal's oral cavity, and (c) delivering said interferon by absorption through a mammal's oral mucosal tissue.
A particular advantage of the present invention is that the level of interferon in systemic circulation achieved in a mammal with an amount of interferon when administered into a mammal's oral cavity in form of aerosol is greater than the level achievable with the same amount of interferon administered into a mammal's oral cavity in non-aerosol form and under otherwise equal conditions. Accordingly, it is now possible through the practice of this invention to achieve certain desired therapeutic effects using less amount of interferon than was heretofore possible. The desired therapeutic effects achievable through the practice of this invention include all known in the art therapeutic effects of interferon. Such effects include, but are not limited to, antiviral, antiproliferative, antitumor, antibacterial, and immunoregulatory action of interferon in mammals. Therefore, in practicing this invention, it is possible to minimize potential adverse effects, which may be associated with larger, therapeutic doses of the interferon and still achieve the therapeutic effect.
As used herein, the term "aerosol" means a colloidal system consisting of very finely divided solid particles or liquid droplets dispersed in and surrounded by a gas.
The present invention is not limited in any way to a specific device for aerosol preparation but is applicable to all such devices now known or subsequently developed. The therapeutically effective amount of interferon is within the skill of those who practice in the art having the benefit of the disclosure herein. Typically, interferon will be present in method of the invention in amounts within its normal or less dosage unit and daily regimen ranges as detailed in medical literature. The dosage range will be from about 100 IU to about 5x106 IU interferon per mammal. Preferably, mammals are administered about 3x106 IU human recombinant interferon-alpha per mammal per day. The present invention is not limited in any way to specific interferon but is applicable to all such interferon now known or subsequently discovered or developed. Nonetheless, a preferred interferon for use in the method of this invention is human recombinant interferon-alpha.
The interferon formulation may be formulated with various pharmaceutically acceptable carriers or diluents in the form of liquid aerosols, solid aerosols, or sprays. Such carriers can include solid diluents, sterile aqueous media, non-toxic organic solvents, and etc.
The interferon formulation may be formulated with various pharmaceutical ingredients known from the art. These ingredients may include, but are not limited to, buffering agents (such as phosphate buffer, carbonate buffer, tris buffer, tartrate buffer, borate buffer, acetate buffer, or maleate buffer), colorants, flavorants, coating agents, suspending agents, sweetening agents, anti-fungal preservatives, antimicrobial preservatives, clarifying agents, antioxidants, surfactants, and tonicity agents. The interferon formulation may be formulated with various pharmaceutically acceptable absorption promoters known from the art. Such absorption promoters may include, but are not limited to, as lecithin, fatty acids, chitosan, salicylates, amino acids, emulsifiers like polyoxyethylene alkyl esters and sodium lauryl sulfate, caproic acid, lactic acid, malic acid, citric acid, pyrrolidonecarboxylic acid, N-alkylpyrrolidones, benzalkonium chloride, cetylpyridinium chloride, cetyltrimethylammonium bromide, cyclodextrins, dextran sulfate, lauric acid, lysophosphatidylcholine, menthol, methoxysalicylate, methyl oleate, polyoxyethylene, polysorbate, sodium glycocholate, sodium glycodeoxycholate, sodium taurocholate, sulfoxides, various alkyl glycosides, etc. The following examples are presented to demonstrate the invention. The examples are illustrative only and are not intended to limit the scope of the invention in any way. EXAMPLE 1
This example shows that sublingual administration of interferon in form of aerosol resulted in improved transmucosal delivery of interferon.
Materials. Human recombinant interferon-alpha2b (rhlFN-alpha) was from (Cytokine Ltd., St. Petersburg, Russia).
Assay. Human interferon-alpha ELISA assay (Cytokine Ltd., St. Petersburg, Russia) was used. Mice. Male C57BL mice 10- to 12-week aged were used.
Procedure. Mice were subdivided into three groups. Mice in the first group (control 1) received sublingually solution of 2.5 μg (0.5χ106 IU) rhlFN-alpha dissolved in 0.1 ml of saline (pH 7.2). Mice in the second group (control 2) received intramuscularly 2.5 μg (0.5x106 IU) of rhlFN-alpha dissolved in 0.1 ml of saline (pH 7.2). Mice in the third group received sublingually 2.5 μg (0.5x106 IU) rhlFN-alpha in form of liquid aerosol by the following method: parent solution of 2.5 μg (0.5x106 IU) rhlFN-alpha was prepared by dissolution of 2.5 μg (0.5x106 IU) rhlFN-alpha in 0.1 ml of saline (pH 7.2), this solution was sprayed by nebulizer to form liquid aerosol consisting of liquid droplets with mass median aerodynamic diameter from 8 to 150 μm, and this aerosol was administered to field under tongue in mouse's oral cavity. Absorption of rhlFN-alpha through oral mucosa into systemic circulation was assayed in the course of time with human interferon alpha ELISA.
Data are presented in Table 1 as mean ± SD (n = 5) of rhlFN-alpha levels in plasma of mice in comparison with control 1 and control 2.
Table 1. Time course of the plasma rhlFN-alpha levels.
Figure imgf000005_0001
Figure imgf000006_0001
*Differs significantly of Control 1 (p < 0.001) 'Differs significantly of Control 2 (p < 0.001)
As shown in Table 1 , the sublingual administration of interferon in liquid aerosol form resulted in improved transmucosal delivery of interferon into systemic circulation which delivery is significantly much greater as compared to administration of the same amount of interferon in liquid sublingual non-aerosol form and under otherwise equal conditions (control 1).
Furthermore, the sublingual administration of interferon in liquid aerosol form resulted in improved transmucosal delivery of interferon into systemic circulation which delivery is significantly much faster and much greater as compared to intramuscular administration of the same amount of interferon and under otherwise equal conditions (control 2).
EXAMPLE 2
This example shows that sublingual administration of interferon formulation comprising interferon and an absorption promoter in form of aerosol resulted in improved transmucosal delivery of interferon.
Procedure. Mice were subdivided into two groups. Mice in the first group (control) received sublingually solution of 2.5 μg (0.5χl06 IU) rhlFN-alpha dissolved in 0.1 ml of saline (pH 7.2) with addition of 0.01 mg soy lecithin as the absorption promoter. Mice in the second group received sublingually interferon formulation comprising 2.5 μg (0.5x106 IU) rhlFN-alpha in form of liquid aerosol by the following method: parent solution of 2.5 μg (0.5x106 IU) rhlFN-alpha was prepared by dissolution of 2.5 μg (0.5x106 IU) rhlFN-alpha in 0.1 ml of saline (pH 7.2) with addition of 0.01 mg soy lecithin as the absorption promoter, this solution was sprayed by nebulizer to form liquid aerosol consisting of liquid droplets with mass median aerodynamic diameter from 8 to 150 μm, and this aerosol was administered to field under tongue in mouse's oral cavity. Absorption of rhlFN-alpha through oral mucosa into systemic circulation was assayed in the course of time with human interferon alpha ELISA.
Data are presented in Table 2 as mean ± SD (n = 5) of rhlFN-alpha levels in plasma of mice in comparison with control.
Table 2. Time course of the plasma rhlFN-alpha levels.
Figure imgf000007_0001
*Differs significantly of Control (p < 0.001)
As shown in Table 2, the sublingual administration of interferon formulation comprising interferon and an absorption promoter in liquid aerosol form resulted in improved transmucosal delivery of interferon into systemic circulation which delivery is significantly much greater as compared to administration of the same amounts of interferon and the absorption promoter in liquid sublingual non-aerosol form and under otherwise equal conditions (control).

Claims

We claim:
1. A method for oral transmucosal delivery of interferon comprising the steps of: (a) providing an interferon formulation comprising a therapeutically effective amount of interferon,
(b) administering said interferon formulation in form of aerosol consisting of solid particles or liquid droplets with mass median aerodynamic diameter from 4 to 150 μm sublingually into a mammal's oral cavity, and (c) delivering said interferon by absorption through a mammal's oral mucosal tissue.
2. The method of Claim 1 wherein said therapeutically effective amount of interferon is about 100 IU to about 5x106 IU per mammal.
3. The method of Claim 1 wherein said interferon is a human recombinant interferon alpha.
PCT/RU2002/000300 2002-06-20 2002-06-20 Method for oral transmucosal delivery of interferon WO2004000266A1 (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004103396A1 (en) * 2003-05-08 2004-12-02 Nastech Pharmaceutical Inc. Compositions for enhanced mucosal delivery of interferon alpha
WO2016169571A1 (en) * 2015-04-20 2016-10-27 Ghaleb Haider Abbas Pharmaceutical product for treatment & prophylaxis of viral/ microbial infection
US20210228687A1 (en) * 2018-06-01 2021-07-29 Ilc Therapeutics Ltd Compositions and methods relating to the treatment of diseases

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5017371A (en) * 1988-01-06 1991-05-21 Amarillo Cell Culture Company, Incorporated Method for reducing side effects of cancer therapy
WO1992010207A1 (en) * 1990-12-14 1992-06-25 Schering Corporation Oral administration of alpha interferon to treat lung malignancies
WO1997025862A1 (en) * 1996-01-19 1997-07-24 Mcgill University Hepatitis pretreatment composition and method
WO2001049260A2 (en) * 1999-12-30 2001-07-12 Intermune, Inc. Y-ifn liquid-droplet aerosol and method

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5017371A (en) * 1988-01-06 1991-05-21 Amarillo Cell Culture Company, Incorporated Method for reducing side effects of cancer therapy
WO1992010207A1 (en) * 1990-12-14 1992-06-25 Schering Corporation Oral administration of alpha interferon to treat lung malignancies
WO1997025862A1 (en) * 1996-01-19 1997-07-24 Mcgill University Hepatitis pretreatment composition and method
WO2001049260A2 (en) * 1999-12-30 2001-07-12 Intermune, Inc. Y-ifn liquid-droplet aerosol and method
US20010043906A1 (en) * 1999-12-30 2001-11-22 Vlasselaer Peter Van gamma-IFN liquid-droplet aerosol and method

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
HARRIS D ET AL: "DRUG DELIVERY VIA THE MUCOUS MEMBRANES OF THE ORAL CAVITY", JOURNAL OF PHARMACEUTICAL SCIENCES, AMERICAN PHARMACEUTICAL ASSOCIATION. WASHINGTON, US, vol. 81, no. 1, 1992, pages 1 - 10, XP000247003, ISSN: 0022-3549 *
LECCIONES J A ET AL: "A pilot double-blind, randomized, and placebo-controlled study of orally administered IFN-alpha-n1 (Ins) in pediatric patients with measles.", JOURNAL OF INTERFERON & CYTOKINE RESEARCH: THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY FOR INTERFERON AND CYTOKINE RESEARCH. UNITED STATES SEP 1998, vol. 18, no. 9, September 1998 (1998-09-01), pages 647 - 652, XP001135200, ISSN: 1079-9907 *
RUSSELL I J ET AL: "Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: effects of low-dose, sublingual use of human interferon-alpha.", JOURNAL OF INTERFERON & CYTOKINE RESEARCH: THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY FOR INTERFERON AND CYTOKINE RESEARCH. UNITED STATES AUG 1999, vol. 19, no. 8, August 1999 (1999-08-01), pages 969 - 978, XP001145919, ISSN: 1079-9907 *
SENEL SEVDA ET AL: "Delivery of bioactive peptides and proteins across oral (buccal) mucosa.", CURRENT PHARMACEUTICAL BIOTECHNOLOGY, vol. 2, no. 2, June 2001 (2001-06-01), June, 2001, pages 175 - 186, XP001135244, ISSN: 1389-2010 *
VEUILLEZ F ET AL: "Factors and strategies for improving buccal absorption of peptides", EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, ELSEVIER SCIENCE PUBLISHERS B.V., AMSTERDAM, NL, vol. 51, no. 2, March 2001 (2001-03-01), pages 93 - 109, XP004257246, ISSN: 0939-6411 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004103396A1 (en) * 2003-05-08 2004-12-02 Nastech Pharmaceutical Inc. Compositions for enhanced mucosal delivery of interferon alpha
WO2016169571A1 (en) * 2015-04-20 2016-10-27 Ghaleb Haider Abbas Pharmaceutical product for treatment & prophylaxis of viral/ microbial infection
US20210228687A1 (en) * 2018-06-01 2021-07-29 Ilc Therapeutics Ltd Compositions and methods relating to the treatment of diseases

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