Bromelain Bromelain is an enzyme extract derived from the stems of pineapples, although it exists in all parts of the fresh pineapple. The extract has a history of folk medicine use. As an ingredient, it is used in cosmetics, as a topical medication, and as ...

, a concentrate of

proteolytic enzyme A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...

s from the

pineapple The pineapple (''Ananas comosus'') is a tropical plant with an edible fruit; it is the most economically significant plant in the family Bromeliaceae. The pineapple is indigenous to South America, where it has been cultivated for many centuri ...

plant, is used in medicine. It is approved in the European Union for the

debridement Debridement is the medical removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue. Removal may be surgical, mechanical, chemical, autolytic (self-digestion), and by maggot therapy. In p ...

(removal of

eschar An eschar (; Greek: ''ἐσχάρᾱ'', ''eskhara''; Latin: ''eschara'') is a slough or piece of dead tissue that is cast off from the surface of the skin, particularly after a burn injury, but also seen in gangrene, ulcer, fungal infections, ...

, that is dead and damaged tissue) of severe

burn A burn is an injury to skin, or other tissues, caused by heat, cold, electricity, chemicals, friction, or ultraviolet radiation (like sunburn). Most burns are due to heat from hot liquids (called scalding), solids, or fire. Burns occur mainl ...

wounds under the brand name Nexobrid. It was developed by MediWound. The medicine has been granted

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

status by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA). In other contexts, bromelain has been researched for possible anti-inflammatory effects in treating a range of conditions or diseases, but results of these studies are mixed and regarded as preliminary. In December 2022, anacaulase-bcdb (Nexobrid) was approved for medical use in the United States.

Medical uses

In the United States, anacaulase gel is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for eschar removal in adults with deep partial thickness and/or full thickness thermal burns. The medication is approved for burns of degrees IIb, i.e. deep partial skin thickness burns, to III, i.e. full thickness burns, and has been shown to significantly reduce the necessity of surgical debridement (15% versus 63% under standard treatment) and skin transplants (18% versus 34%) in a

randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...

. The concentrate is solved in a sterile

gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still dif ...

basis, applied onto the burn wound, covered with a wound dressing, and removed after four hours. The healthy surrounding skin has to be protected with a sterile

paraffin Paraffin may refer to: Substances * Paraffin wax, a white or colorless soft solid that is used as a lubricant and for other applications * Liquid paraffin (drug), a very highly refined mineral oil used in cosmetics and for medical purposes * Alkane ...

ointment. The EMA recommends that the treatment should be used in only hospitals having specialised burns centres.

Contraindications and adverse effects

Predictably, the bromelain gel is contraindicated in persons allergic to pineapple or the enzyme

papain Papain, also known as papaya proteinase I, is a cysteine protease () enzyme present in papaya (''Carica papaya'') and mountain papaya (''Vasconcellea cundinamarcensis''). It is the namesake member of the papain-like protease family. It has wide ...

. The most common side-effects are

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

(19% of patients in studies) and local pain (3.6%). Wound infections occur no more frequently than under standard treatment.

Interactions

The enzymes in NexoBrid inhibit the liver enzymes

CYP2C8 Cytochrome P4502C8 (abbreviated CYP2C8), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-cha ...

and

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...

when ingested. These are involved in the breaking down of a number of drugs, including

amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibrilla ...

chloroquine Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...

, and

warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...

. It is not known whether this mechanism has any clinical relevance.

Pharmacokinetics

Depending on the surface area and depth of the wound, bromelain blood serum concentrations of no more than 40 µg/ml are expected, with peak concentrations reached after 2 to 4 hours. The terminal half-life varied between 8.5 and 19.9 hours in studies. These data have been obtained from 15 patients with comparatively shallow wounds.

Chemistry

The medication is extracted from the stem of the pineapple plant (''Ananas comosus'') by a standardised process, and each lot has to be analysed for its chemical composition. It contains a mixture of proteolytic enzymes, the main compound being stem bromelain. Bromelain is thought to be the active ingredient, but this has not been determined in studies. The gel basis contains water,

polyacrylic acid Poly(acrylic acid) (PAA; trade name Carbomer) is a polymer with the formula (CH2-CHCO2H)n. It is a derivative of acrylic acid (CH2=CHCO2H). In addition to the homopolymers, a variety of copolymers and crosslinked polymers, and partially deproto ...

as a

gelling agent A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still di ...

, and a

disodium hydrogen phosphate Disodium phosphate (DSP), or disodium hydrogen phosphate, or sodium phosphate dibasic, is the inorganic compound with the formula Na2HPO4. It is one of several sodium phosphates. The salt is known in anhydrous form as well as forms with 2, 7, 8 ...

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly caustic base and alkali ...

buffer Buffer may refer to: Science * Buffer gas, an inert or nonflammable gas * Buffer solution, a solution used to prevent changes in pH * Buffering agent, the weak acid or base in a buffer solution * Lysis buffer, in cell biology * Metal ion buffer * ...

References

External links

* {{Portal bar , Medicine Preparations for treatment of wounds and ulcers Hydrolases Orphan drugs