Compositions capable of facilitating penetration across a biological barrier

Inactive Publication Date: 2005-10-20
CHIASMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012] The present invention provides compositions for effectively translocating therapeutically active molecules, i.e., effectors, otherwise impermeable through biological barriers, by including such molecules in a water soluble composition. In one embodiment, the water soluble composition can be immer

Problems solved by technology

Active or facilitative transport occurs via cellular carriers, and is limited to transport of low molecular weight degradation products of complex molecules such as proteins and sugars, e.g., amino acids, pentoses, and hexoses.
This process is limited to relatively small hydrophobic compounds.
Consequently, with the exception of those molecules that are transported by active or facilitative mechanisms, absorption of larger, more hydrophilic molecules is, for the most part, limited to the paracellular pathway.
However, the entry of molecules through the paracellular pathway is primarily restricted by the presence of the tight junctions.
However, one drawback to all of these methods is that they facilitate the indiscriminate penetration of any nearby molecule that happens to be in the gastrointestinal or airway lumen.
In addition, each of these intestinal/respiratory absorption enhancers has properties that limit their general usefulness as a means to promote absorptio

Method used

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  • Compositions capable of facilitating penetration across a biological barrier
  • Compositions capable of facilitating penetration across a biological barrier
  • Compositions capable of facilitating penetration across a biological barrier

Examples

Experimental program
Comparison scheme
Effect test

example 1

Utilization of Compositions of the Instant Invention to Enable the Effective Translocation of Insulin Across an Epithelial Barrier

a) Measurement of Blood Glucose Levels in Rats:

[0115] A composition contemplated by the instant invention was prepared by dissolving human insulin with spermine and phytic acid in double distilled water (“DDW”) containing NaOH. The solution was then lyophilized and suspended with sodium dodecanoate (SD), octanol and geraniol in a mixture of mineral oil, medium chain triglyceride (MCT) oil and castor oil. Components and concentrations are detailed in Table 1.

TABLE 1Composition for insulin translocationh-Insulin in10% SDMineral oil:7 mM NaOHSperminePhytic acidinOctanol:MCT:in DDW(50 mg / ml in(50 mg / mlLyoph-PropyleneGeraniolCastor oilSoni-Insulin(pH 9.0)DDW)in DDW)ilizationGlycol1:11:1:1cationconcentration1mg / 0.5mg0.25mg90 μl90 μl820 μl30″1 mg / ml985μl(10μl)(5μl)

[0116] Eight male SD rats, 175-200 gr, were deprived of food, 18 hours prior to the experiment...

example 2

Utilization of Compositions of the Instant Invention to Enable the Effective Translocation of Heparin Across an Epithelial Barrier

[0128] The composition used for this study was prepared by dissolving human unfractionated heparin with spermine, and sodium dodecanoate in DDW containing NaOH. The solution was then lyophilized and suspended with octanol and geraniol in a mixture of medium chain triglyceride (MCT) oil and castor oil further containing sorbitan monopalmitate (Span-40), methylcellulose (MC-400), glyceryl monooleate, and pluronic (F-127). Components and concentrations are detailed in Table 8.

TABLE 8Composition for heparin translocation1% Span-40, 2% GMO,1% Pluronic F-127,Lyophilization0.2% MC-400 inHeparinSpermineSDin 7 mM NaOHGeraniolOctanolMCT:Castor Oil 1:210 mg5 mg180 μl100 μl100 μl800 μl

[0129] Five male CB6 / F1 mice, 9-10 wks, were divided into 2 groups, and anesthetized by a solution of 85% ketamine, 15% xylazine, 0.01 ml / 10 g of body weight. Each preparation was ad...

example 3

Utilization of Compositions of the Instant Invention to Enable the Effective Translocation of Interferon Alpha Across an Epithelial Barrier

[0131] A composition contemplated by the instant invention was prepared by dissolving human interferon alpha with spermine, polyvinylpyrrolidone (PVP-40) and sodium dodecanoate (SD) in DDW containing NAOH. The solution was then lyophilized and suspended with octanol and geraniol in a mixture of medium chain triglyceride (MCT) oil and castor oil further containing sorbitan monopalmitate (Span-40), methylcellulose (MC-400), and glyceryl monooleate (GMO). Components and concentrations are detailed in Table 10.

TABLE 10Composition for interferon alpha translocation1% Span-40,7 mMPVP-40,0.2% MC-400,INF-αNaOHSpermine(200 mg / 2% GMO, inINF-α(200 μg / ml)in(50 mg / mlml in10% SDLyoph-MCT:CastorSoni-concen-in PBSDDWin DDW)DDW)in DDWilizationGeraniolOctanoloil 1:2cationtration250μl375 μl0.5mg2.5mg45 μl25 μl25 μl450 μl30″100 μg / ml(50μg)(10μl)(25μl)

[0132] Six m...

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Abstract

This invention relates to novel penetrating compositions including one or more effectors included within a water soluble composition, immersed in a hydrophobic medium. The invention also relates to methods of treating or preventing diseases by administering such penetrating compositions to affected subjects.

Description

RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Application No. 60 / 562,345, filed on Apr. 15, 2004, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION [0002] This invention relates to novel penetration compositions that enable efficient translocation of an effector across biological barriers. BACKGROUND OF THE INVENTION [0003] Techniques enabling efficient transfer of a substance of interest across a biological barrier are of considerable interest in the field of biotechnology. For example, such techniques may be used for the transport of a variety of different substances across a biological barrier regulated by tight junctions (i.e., the mucosal epithelia, which include the intestinal and respiratory epithelia and the vascular endothelia, which includes the blood-brain barrier). [0004] The intestinal epithelium represents the major barrier to absorption of orally administered compounds, e.g., drugs and peptides, into th...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K9/127A61K38/18A61K38/19A61K38/20A61K38/21A61K38/23A61K38/24A61K38/26A61K38/28A61K38/29A61K38/33A61K38/34A61K38/54A61K38/55A61K38/58A61K47/44
CPCA61K9/0014A61K2039/541A61K9/0031A61K9/0043A61K9/0053A61K31/727A61K38/212A61K38/26A61K38/28A61K47/10A61K47/12A61K47/32A61K47/44A61K39/07A61K9/0019A61K2300/00A61P13/12A61P15/08A61P19/10A61P25/00A61P25/14A61P25/16A61P25/24A61P25/28A61P27/16A61P29/00A61P3/00A61P3/02A61P3/04A61P31/04A61P31/10A61P31/12A61P33/00A61P35/00A61P37/02A61P5/00A61P7/00A61P7/02A61P7/06A61P9/10A61P3/10A61K9/10
Inventor BEN-SASSON, SHMUEL A.
Owner CHIASMA INC
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