Quillaja saponin mixture

QUILLAIA BARK Quillajae cortex is the bark of Quillaja saponaria, Molina, family Rosaceae, from which the cork is removed. This species is an evergreen tree in Chile (in the valleys of the Cordilleras), Peru and Bolivia. The drug consists of the inner bark which is generally cut before marketing. It has an acrid taste and causes sneezing. The bark contains about 10% of a saponin mixture (Quillaia saponin), which besides its use as an expectorant also has a technical use and as an adjuvant in some vaccines as the saponin potentiates the immunising power of the vaccine. 

Fig. 3a/b In the ly range from solvent start till =0.5 the brown zones of the triterpene glycosides (saponins) of Semen Vaccariae such as vaccarosides A-1, vaccaroid B or segetoside A-I acid are visible. As reference is applied the saponin mixture of Quillaja (T2). In the upper TLC-range from I =0.85 till the solvent front appear the corresponding sapogenins (triterpenoic acids) of Semen Vaccariae in red-violet colour. 

It is marketed as, and has been described to be, a potent adjuvant which has found widespread use in veterinary vaccines against, for example, foot and mouth disease, rabies, and in a number of experimental vaccines and in preclinical trials. Unfortunately its hemolytic activity and local counter reactions make it unsuitable for human vaccines [5]. Furthermore, Quil A is used for production of ISCOMs (immunostimulating complexes, typically composed of 0.5 % Quillaja saponins, 0.1% cholesterol, 0.1% phospholipid and antigen dissolved in PBS). Although side effects of Quil A were almost absent when incorporated into ISCOM, this form of vaccine is only used for veterinary vaccines and has not been approved for humans. Quil A is still a heterogeneous mixture, consisting of up to 23 different individual saponins detectable by HPLC [8]. Later, it was observed that not all saponins were active as adjuvants. A saponin termed QS III was purified from of a methanol extract of Quillaja bark by several chromatographic steps, it has, however, not been tested for adjuvant activity [12]. 

Quil A has been the major saponin mixture used for ISCOM work to date. The major modification to ISCOM technology has been the use of three HPLC-fractions of Quillaja saponaria bark aqueous extract named QH-A, QH-B and QH-C [47]. The ratio 7 0 3 for these fractions known as ISCOPREP 7.0.3. has been recently tested as a component of a new ISCOM-adjuvanted human influenza vaccine. 

Saponins are a family of glycosides (sugar derivatives) widely distributed in plants. Each saponin consists of a sugar moiety bound to a sapogenin (either a steroid or a triterpene). The immunostimulatory properties of the saponin fraction isolated from the bark of Quillaja (a tree) has been long recognized. Quil A (which consists of a mixture of related saponins) is used as an adjuvant in selected veterinary vaccines. However, its haemolytic potential precludes its use in human vaccines. Research efforts continue in an attempt to identify individual saponins (or derivatives thereof) that would make safe and effective adjuvants for use in human medicine. 

Quillaia bark or soapbark is derived from the tree Quillaja saponaria (Rosaceae) and other Quillaja species found in Chile, Peru, and Bolivia. The bark contains up to 10% saponins, a mixture known as commercial saponin , which is used for its detergent properties. Quillaia s surfactant properties are occasionally exploited in pharmaceutical preparations where it is used in the form of quillaia tincture as an emulsifying agent, particularly for fats, tars, and volatile oils. The bark contains a mixture of saponins which on hydrolysis liberates quillaic acid (Figure 5.62) as the aglycone, together with sugars, uronic acids, and acids from ester functions. 

The only vaccine adjuvants currently licensed by the FDA are aluminium salts. All other adjuvants are considered experimental and must undergo special preclinical testing. In the search for well-characterized adjuvants, the saponins from Quillaja saponaria, having quillaic acid as aglycone were shown to be potent immune adjuvants, such as Quil A (a purified mixture of 23 saponins), Iscoprep 7 0 3 which is a mixture of well characterized saponin fraction QH-A, QH-B, QH-C in a ratio 7 0 3 and the pure saponins QS-7, QS-17, QS-18, QS-21 (31) [41] (see Fig. (2)) and QS-L1 (32) [42]. 

Three saponin fractions of interest (QH-A, QH-B, QH-C) have been obtained from an aqueous extract of the Quillaja bark by reversed HPLC according to their elution profile. The mixture of these compounds in a ratio 7 0 3 knovvm as ISCO-PREP 7.0.3 has recently been tested as a component of a new ISCOM-adjuvanted human influenza vaccine. ... 

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