Drug delivery from rapid gelling polymer composition

A composition and compound technology, applied in the direction of drug delivery, pharmaceutical formulation, etc., can solve problems such as increased tissue inflammation and deterioration

Inactive Publication Date: 2006-04-05
ANGIOTECH INT AG (CH)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

One difficulty encountered in designing compositions that form hydrogels in situ is that optimization of

Method used

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  • Drug delivery from rapid gelling polymer composition
  • Drug delivery from rapid gelling polymer composition
  • Drug delivery from rapid gelling polymer composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0605] Preparation of Two-Component Tissue Sealant Compositions

[0606] a. The first component

[0607] Pentaerythritol poly(ethylene glycol) ether tetra-succinimidyl glutarate ("SG-PEG") (molecular weight 10,000) was dissolved at a concentration of 20% w / v in 0.5 mM sodium phosphate pH 6.0. (Due to the susceptibility of the active ester to hydrolysis, this solution is not stable in aqueous media and should be used within one hour of preparation).

[0608] b. Second component

[0609] Pentaerythritol poly(ethylene glycol) ether tetra-mercapto (molecular weight 10,000) was dissolved in 300 mM sodium phosphate / sodium carbonate buffer ("P / C buffer") pH 9.6 at a concentration of 20% w / v. P / C buffer was prepared as follows: 300 mM sodium dihydrogen phosphate was mixed with 300 mM sodium carbonate to reach pH 9.6. The final molarity was approximately 117 mM phosphate and 183 mM carbonate. The solution is stable in aqueous media, but care should be taken to avoid e...

Embodiment 2

[0611] Surgical closure of animals

[0612] The right carotid artery of New Zealand white rabbits was exposed. The rabbits were treated with 200 U / kg of heparin and the vessels were clamped proximally and distally with atraumatic hemostatic clips. A puncture hole was made in the carotid artery using a 27G needle. Control rabbits were treated with tampon until hemostasis was achieved. For treated rabbits, approximately 0.5 mL each of the two components of the composition prepared as described in Example 1 was delivered to the defect site using a two-component nebulizer (Duo Flow, Hemaedics, Malibu, Calif.) point. After the material was in place for 30 seconds, the clamp was removed and the hemostasis time and blood loss were measured. The arteries of control rabbits were also kept in constant clamp for 30 seconds for consistency. The results are shown in Table 1.

[0613] Blood loss and hemostasis time as a function of treatment

[0614] The abo...

Embodiment 3

[0616] Surgical closure of ePTFE grafts

[0617] Dogs were treated with heparin to achieve an activated clotting time greater than 480 seconds. The dog's left iliac artery was exposed and isolated with proximally and distally placed atraumatic hemostatic clips. A 5 cm section of the artery was excised and replaced with an ePTFE (polytetrafluoroethylene) graft of the same diameter. The graft was deaired using a 27G needle prior to completion of anastamosis. The two components of the composition prepared according to Example 1 were delivered to the defect site at approximately 3.0 mL each using a two-component nebulizer (Cohesion Technologies, Inc., Palo Alto, Calif.). After the material was in place for 30 seconds, the clamp was removed and the hemostasis time and blood loss were measured. Except for material application, the procedure was repeated on the left iliac artery. The right iliac artery received tamponade only. The results are shown in Table 2...

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Abstract

Compositions are disclosed that afford drug delivery from two-part polymer compositions that rapidly form covalent linkages when mixed together. Such compositions are particularly well suited for use in a variety of tissue related applications when rapid adhesion to the tissue and gel formation is desired along with drug delivery. For example, the compositions are useful as tissue sealants, in promoting hemostasis, in effecting tissue adhesion, in providing tissue augmentation, and in the prevention of surgical adhesions.

Description

Background of the invention [0001] field of invention [0002] The present invention generally relates to compositions that provide drug delivery from two-part polymer compositions that are mixed together to rapidly form covalent bonds. These compositions are particularly suitable for use in many tissue-related applications when rapid adhesion to tissue and gel formation are required for concomitant drug delivery. For example, these compositions are used as tissue sealants in promoting hemostasis, in affecting tissue adhesion, in providing tissue augmentation, and in preventing surgical adhesions. [0003] Description of related fields [0004] The use of polymer compositions, especially those consisting of synthetic polymers, is now widely recognized in tissue engineering. Unlike many naturally derived compositions, synthetic polymer compositions can be formulated to exhibit predetermined physical characteristics, such as gel strength, and biological characteristics, su...

Claims

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Application Information

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IPC IPC(8): A61K9/00
Inventor D·M·格雷维特A·陶卡克斯－麦克斯P·M·特雷克斯A·迈蒂L·恩布里
Owner ANGIOTECH INT AG (CH)
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