Heparin, sodium salt

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Insufficient details available to make a reliability assessment.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Materials and methods

Type of study / information:

This study was set up to evaluate the effect of nebulized low molecular weight test substance on spirometric parameters and selected markers of allergic inflammation in bronchial asthma.

Endpoint addressed:

not applicable

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study was set up to evaluate the effect of nebulized low molecular weight test substance on spirometric parameters and selected markers of allergic inflammation in bronchial asthma.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

nonasodium 2-({6-[(2-carboxylato-4-hydroxy-6-{[6-hydroxy-5-(sulfonatoamino)-4-(sulfonatooxy)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-5-(sulfonatooxy)oxan-3-yl)oxy]-4-hydroxy-5-(sulfonatoamino)-2-[(sulfonatooxy)methyl]oxan-3-yl}oxy)-4-hydroxy-3-(sulfonatooxy)-3,4-dihydro-2H-pyran-6-carboxylate

EC Number:

700-834-1

Cas Number:

9041-08-1

Molecular formula:

not applicable (UVCB substance)

IUPAC Name:

nonasodium 2-({6-[(2-carboxylato-4-hydroxy-6-{[6-hydroxy-5-(sulfonatoamino)-4-(sulfonatooxy)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-5-(sulfonatooxy)oxan-3-yl)oxy]-4-hydroxy-5-(sulfonatoamino)-2-[(sulfonatooxy)methyl]oxan-3-yl}oxy)-4-hydroxy-3-(sulfonatooxy)-3,4-dihydro-2H-pyran-6-carboxylate

Test material form:

not specified

Details on test material:

Batch No.: not specified
Purity: not specified

Method

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

At the beginning and at the end of the experiment every patient underwent bronchoscopy with BAL and in 15 of them bronchial biopsy was performed. Blood was drawn for ECP evaluation. The low molecular weight test substance was administered in nebulization in a dose 5000 U Xa/day for two weeks. BALf cellularity was evaluated as well as BALf IL-5 concentration. Further ELAM-1 and VCAM-1 expression in bronchial mucosa was examined in immunohistochemistry.

Exposure assessment:

measured

Details on exposure:

At the beginning and at the end of the experiment every patient underwent bronchoscopy with BAL and in 15 of them bronchial biopsy was performed. Blood was drawn for ECP evaluation. The low molecular weight test substance was administered in nebulization in a dose 5000 U Xa/day for two weeks. BALf cellularity was evaluated as well as BALf IL-5 concentration. Further ELAM-1 and VCAM-1 expression in bronchial mucosa was examined in immunohistochemistry.

Results and discussion

Results:

The test substance treatment significantly enhanced FEV1 from 76.02 +/- 21.7% nominate value before to 92.4 +/- 21.8% after treatment (p < 0.005). Cellular profile of BALf changed, showing significant drop in percentages of eosinophils--from 7% to 6% (p < 0.05), macrophages--38 to 32% (p < 0.05) and neutrophils--32 to 28% (p < 0.05). Surprisingly there was no any change in ECP concentration in blood serum or IL-5 in BALf. Also adhesion molecules expression in bronchial mucosa remained unchanged.

Applicant's summary and conclusion

Conclusions:

Chronic low molecular weight test substance nebulization is a valuable treatment ameliorating asthmatic condition clearly due to anti-inflammatory properties of test substance. Both dose of low molecular weight test substance used and the time of therapy have to be further investigated in order to develop treatment able to influence more of the elements of allergic inflammation.