Initially, crude collagenase manufactured and sold by Worthington Biochemicals in the early 1960’s and later by Sigma-Aldrich. These products are minimally processed bacterial culture supernatants. Later, Sigma manufactured Collagenase Type XI, an enriched collagenase product prepared by further processing of crude collagenase. Enriched collagenase has higher enzyme activities than found in crude collagenase. All these products can be classified as “poorly defined” collagenase because the biochemical composition reflects the composition of the bacterial culture supernatant. Each lot of product is unique. No attempt is made to dramatically alter the enzyme composition, Collagenase represents 3-8 and 10-20% of the dry weight of crude and enriched collagenase, respectively.

In 1994, Boehringer Mannheim Biochemicals introduced the Liberase Purified Enzyme Blend product line. The Liberase products were purified enzyme mixtures containing class I (C1) and class II (C2) collagenase and a neutral protease. The Liberase products created a new product category: “defined collagenase.” with Liberase categorized as a purified, defined collagenase enzyme mixture. These products are more expensive than poorly defined crude or enriched collagenase products because collagenase had to separated from other proteins in the culture supernatant, then class I and class II collagenase was separately purified, then recombined in the final product. 

In 2015, VitaCyte introduced a purified defined collagenase products for research use where the collagenase is > 85% pure and consists primarily of undegraded enzyme. PD Collagenase (formerly known as DE Collagenase), Collagenase Gold that has characteristics similar to the Liberase products at a much lower cost since there was no need to perform downstream purification of the enzyme. These products are priced similarly to crude or enriched collagenase products.

The table below summarizes the products offered by different primary collagenase suppliers (i.e., suppliers that manufacture and sell collagenase products). Nordmark and VitaCyte offer animal origin free versions of purified collagenase and neutral protease products. Nordmark, Roche, and VitaCyte offer GMP Grade versions of many of their products. 

 

Poorly Defined Products

SupplierProduct CategoryProduct NamesComments
NordmarkCrudeNB-4, NB-5, NB-6, NB-8
SigmaCrudeTypes I, IASimilar to Worthington Type 1
SigmaCrudeTypes II, IV, V, VIIITested for specific cell
isolation applications
SigmaCrudeTypes A, B, DRoche products distributed by Sigma
SigmaEnrichedType XI
SigmaEnrichedCollagenase PRoche products distributed by Sigma
WorthingtonCrudeType 1, 2, 3, 4Each have different amounts
of neutral protease
WorthingtonEnrichedType 6, 7

 

Defined Products

SupplierProduct CategoryProduct NamesComments
NordmarkEnrichedNB Protease
NordmarkPurifiedNB-1 Collagenase
NordmarkPurifiedClostripain
RochePurifiedT Flex Kit
RochePurifiedLiberase MTFC1:C2 60:40 mixture
RochePurifiedLiberase MNPC1:C2 60:40 mixture
SigmaPurifiedLiberase Dl, DHRoche products distributed by Sigma
SigmaPurifiedLiberase TL, TM, THRoche products distributed by Sigma
VitaCytePurified DefinedPD Collagenase 100
PD Collagenase 800
All PD products have fixed amount of neutral protease activity with increasing amounts of collagenase activity. The number refers to minimal amount of FALGPA activity per vial in 1 g (100, 800) pack sizes
VitaCytePurified DefinedCollagenase GoldMinimal neutral protease
activity, can substitute for
purified collagenase
VitaCytePurified DefinedCollagenase Gold PlusGMP Grade version of Gold product
VitaCytePurifiedCollagenase HAC1:C2 60:40 mixture
VitaCytePurifiedCollagenase MAC1:C2 60:40 mixture
VitaCytePurifiedThermolysin
VitaCytePurifiedBP Protease
VitaCytePurifiedClostripain
VitaCytePurifiedRIC1:C2 60:40 mixture
VitaCytePurifiedASC1:C2 60:40 mixture
VitaCytePurifiedrCollagenase HIRecombinant Collagenase