Birch bark extract API Manufacturers

General Description:

Birch bark extract, identified by CAS number 84012-15-7, is a notable compound with significant therapeutic applications. Birch bark extract is rich in triterpenoids with beneficial biological and pharmacological activities. Some of the compounds identified in it include betulin, , , oleanolic acid, and erythrodiol. Birch bark extract is obtained from the white part of the birch tree bark, and the main species of trees used for production are _Betula pendula_ Roth (silver birch) and _Betula pubescens_ Ehrh. (white birch), although hybrids of both species are used as well. Two oleogel formulations of birch bark extract (Oleogel-S10, 10% of triterpene dry extract in sunflower oil) have been approved by the European Medicines Agency. Filsuvez, one of these two formulations, is approved for the treatment of partial thickness wounds in patients with epidermolysis bullosa (EB), a rare group of hereditary disorders of the skin, mucous membranes, and internal epithelial linings characterized by extreme skin fragility and blister development. The EMA marketing authorization for Episalvan was withdrawn by the manufacturer in 2022.

Indications:

This drug is primarily indicated for: Filsuvez, a preparation of birch bark extract, is indicated for the treatment of partial thickness wounds associated with dystrophic and junctional epidermolysis bullosa (EB) in patients 6 months and older. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Birch bark extract undergoes metabolic processing primarily in: Approximately 99% of betulin, one of the main active components of birch bark extract, is metabolized _in vitro_ within 5 hours. The most abundant betulin metabolite was formed through oxidation, methylation, and sulfation, and three other metabolites were formed by sulfation or glucuronidation. Betulin is expected to be metabolized mainly by non-CYP enzymatic pathways (75%). Betulin metabolism by CYP-mediated pathways (25%) is expected to be primarily performed by CYP3A4 and CYP3A5. _In vitro_ studies have shown that betulin induces and inhibits several CYP enzymes; however, birch bark extract administered topically leads to negligible systemic exposure and no drug interaction is expected. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Birch bark extract are crucial for its therapeutic efficacy: For oleogel-S10 (Filsuvez, a preparation of birch bark extract), drug absorption was evaluated by measuring the systemic exposure to betulin, its main component. Betulin venous blood concentrations were measured using a dried blood spot bioanalytical method. In most subjects, betulin levels were below the quantitation limit (10 ng/mL). A minority of subjects had higher venous blood concentrations, no greater than 207 ng/mL. This venous blood concentration is similar to the one detected after ingesting betulin-containing foods. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Birch bark extract is an important consideration for its dosing schedule: This pharmacokinetic property has not been studied. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Birch bark extract exhibits a strong affinity for binding with plasma proteins: Betulin, one of the main active components of birch bark extract, is >99.9% bound to plasma proteins. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Birch bark extract from the body primarily occurs through: This pharmacokinetic property has not been studied. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Birch bark extract is distributed throughout the body with a volume of distribution of: This pharmacokinetic property has not been studied. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Birch bark extract is a critical factor in determining its safe and effective dosage: This pharmacokinetic property has not been studied. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Birch bark extract exerts its therapeutic effects through: Birch bark extract and its main component, betulin, promote wound healing and closure by activating pathways involved in keratinocyte differentiation and migration. Compared to a blinded control gel consisting of refined sunflower oil, beeswax, yellow wax and carnauba wax, Filsuvez (Oleogel-S10, a birch bark extract gel) promotes wound closure in patients with epidermolysis bullosa (EB). This effect was more noticeable in patients with recessive dystrophic EB than in patients with junctional EB (JEB) or dominant dystrophic EB (DDEB). Clinical data supporting the use of Filsuvez in patients with JEB or DDEB is insufficient; therefore, their condition should be evaluated regularly to assess the benefit of continued treatment. Birch bark extract may cause hypersensitivity, and theoretically, an increased risk of skin malignancies associated with the use of Filsuvez cannot be ruled out. Although birch bark extract gel is sterile, wound infection may occur during wound healing. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Birch bark extract functions by: Birch bark extract promotes wound healing; however, the specific mechanism of action has not been fully elucidated. _In vitro_ studies in primary human keratinocytes and fibroblasts and _ex vivo_ studies in porcine skin have shown that the dry extract from birch bark and its component betulin modulate inflammatory mediators. Specifically, pro-inflammatory cytokines such as cyclooxygenase 2 (COX-2), interleukin 6 (IL-6) and interleukin 8 (IL-8) are upregulated at both RNA and protein levels. The anti-inflammatory activity of other birch bark extract components such as oleanolic acid, erythrodiol, betulinic acid, and lupeol has also been reported. Birch bark extract also plays a role in the formation of new skin barriers by promoting cellular proliferation, migration, adhesion, deposition of matrix, and keratinocyte differentiation. The dry extract from birch bark and its components betulin, lupeol, and erythrodiol promote keratinocyte migration. In human keratinocytes, birch bark extract induces keratinocyte differentiation by promoting the expression of differentiation markers such as keratin, type I cytoskeletal 10 (KRT 10) and involucrin (INV) as well as the adhesion protein transglutaminase. Also, It has been suggested that the purified triterpene extract derived from birch bark promotes keratinocyte differentiation by, at least in part, upregulating the non-selective transient receptor potential canonical (subtype) 6 (TRPC6) cation channel. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Birch bark extract is categorized under the following therapeutic classes: Anti-Inflammatory Agents, Anti-inflammatory Agents, Miscellaneous, Biological Products, Complex Mixtures, Cytochrome P-450 CYP2C8 Inhibitors, Cytochrome P-450 CYP2C8 Inhibitors (strength unknown), Cytochrome P-450 Enzyme Inhibitors, Plant Preparations, Triterpenes, Wound Healing. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Birch bark extract include:

• Water Solubility: Not soluble in water