Hybrid matrices and hybrid matrix mixtures

A technology of mixtures and compositions, which is applied in the directions of non-active components of polymer compounds, drug combinations, drug delivery, etc.

Inactive Publication Date: 2002-10-30
TRANSKARYOTIC THERAPIES
View PDF6 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this approach has many theoretical advantages over injecting the product itself, including the possibility that normal cellular feedback mechanisms can be controlled to deliver physiologically appropriate levels of the product, it introduces additional complications

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Hybrid matrices and hybrid matrix mixtures
  • Hybrid matrices and hybrid matrix mixtures
  • Hybrid matrices and hybrid matrix mixtures

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0087] Heparin-Sepharose Hybrid Collagen Matrix (HSHCM) Overview

[0088] HSHCM is produced by mixing together the following components: concentrated Dulbecco's Modified Eagle's Medium (DMEM), collagen (e.g., rat tail type I or a suitable alternative, e.g., human placental type I or type III collagen), Microcarriers (e.g. collagen macroporous microcarriers or porous gelatin microcarriers as described above), uncoated or treated with angiogenic factors, cytokines or growth factors (e.g. basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) or platelet-derived growth factor (PDGF)) coated Heparin-Sepharose(R) beads, and cells expressing the therapeutic protein. In an alternative embodiment, multiple cell lines are mixed into the matrix, one expressing a therapeutic protein of interest and another expressing an angiogenic factor, cytokine or growth factor. A cell line expressing both a therapeutic protein and an angiogenic or growth factor can also be ...

Embodiment II

[0121] This example describes the in vivo implantation of HSHCM prepared as described in Example 1. HSHCM containing uncoated Heparin-Sepharose(R) beads or bFGF-coated Heparin-Sepharose(R) beads (50 [mu]g / ml packed beads; 10 [mu]g total bFGF / matrix) was prepared as described in Table 1. Use 5×10 per 4ml matrix 6 HF743 B1-35 cells formed, which is a plasmid containing pXF8.198 ( figure 1 ) and at 20 000-30 000mU / 24h / 10 6 Cellular levels of human foreskin fibroblast clones expressing hFVIII. More detailed procedures for preparing and transfecting cells suitable for the matrices and mixtures of the present invention are provided in WO93 / 09222 (PCT / US92 / 09627), incorporated herein by reference. HSHCM were kept in culture for 2 days prior to implantation. For subcutaneous infusion of matrix, Rag-2 mice (129S6 / SvEvTac-[KO]Rag2, Taconic Farms) were anesthetized and prepared as follows. Mice were injected intraperitoneally with Avertin at a dose of 0.0175ml / g body weight TM (2% ...

Embodiment III

[0125] HSHCM containing uncoated heparin-Sepharose beads or bFGF-coated heparin-Sepharose beads (50 μg / ml packed beads, 10 μg total bFGF / matrix), and collagen microcarriers or gelatin microcarriers, as shown in Table 1 and Table 2, respectively The preparation. The average cell number per matrix and the hFVIII production per matrix (n=3 matrixes per condition) on the day of implantation are listed in Table 3.

[0126] condition

Cell number (×10 6 )

hFVIII (mU / 24h /

HSHCM)

Collagen microcarriers and uncoated heparin

- Sepharose® beads

4.2

84 989

Gelatin microcarriers and uncoated heparin

- Sepharose® beads

3.9

94 407

Collagen microcarriers and bFGF-coated

Heparin-Sepharose® beads

4.3

138 612

Gelatin microcarriers and bFGF-coated

Heparin-Sepharose® beads

3.5

107 683

[0127] A subcutaneous (SC) cell control was included in the experiment and was ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

A composition having a body of matrix material made up of insoluble collagen fibrils, and disposed therewithin: a) a plurality of vertebrate cells; b) a plurality of microcarriers; and c) an agent such as a factor that promotes vascularization, a cytokine, a growth factor, or ascorbic acid. The invention also features a method of delivering a polypeptide to an animal. The method involves introducing into the animal a fluid mixture containing: a) a population of cultured vertebrate cells genetically engineered to express the polypeptide; and b) a plurality of microcarriers.

Description

[0001] This application claims priority to US Application Serial No. 09 / 413,715, filed October 5, 1999 and US Application Serial No. 09 / 662,037, filed September 14, 2000. [0002] The field of the invention is medical devices for the production and delivery of medically useful substances in vivo or in vitro. Background of the invention [0003] The device used to deliver a medically useful substance can significantly affect its efficacy. The standard route of administration for many of these substances is oral, intravenous or subcutaneous. Each of these has inherent limitations, which can affect the therapeutic effect of the delivered substance. Also, many protein-based drugs have short half-lives and low bioavailability, factors that must be considered in their formulation and delivery. Although many devices have been developed to deliver medically useful substances, including portable pumps and catheters, there remains a great need for improved delive...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K47/26A61K9/00A61K31/375A61K31/557A61K31/5575A61K35/12A61K38/00A61K38/16A61K38/21A61K38/22A61K38/24A61K38/27A61K38/28A61K38/43A61K38/46A61K39/00A61K47/32A61K47/34A61K47/36A61K47/38A61K47/42A61L27/00A61L27/24A61L27/38A61L27/44A61L27/54A61P17/02
CPCA61K9/0024A61L27/24A61L27/3804A61L27/44A61L27/54A61L2300/252A61L2300/254A61L2300/256A61L2300/414A61L2300/438A61P17/02A61P35/00
Inventor R·米尼奥-翰施克J·C·拉姆萨D·阿巴罗斯-克勒
Owner TRANSKARYOTIC THERAPIES
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap