Bromelain Bromelain is an enzyme extract derived from the plant stem, stems of pineapples, although it exists in all parts of the fresh plant and fruit. The extract has a history of folk medicine use. As a culinary ingredient, it may be used as a Meat tender ...

, a concentrate of

proteolytic enzyme A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do t ...

s from the

pineapple The pineapple (''Ananas comosus'') is a Tropical vegetation, 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 culti ...

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), or by maggot therapy. In ...

(removal of

eschar Eschar (; ; ; or ''an'' eschar) is a slough or piece of necrosis, dead tissue that is cast off from the surface of the skin, particularly after a Burn, burn injury, but also seen in gangrene, Ulcer (dermatology), ulcer, mycosis, fungal infection ...

, that is dead and damaged tissue) of severe

burn A burn is an injury to skin, or other tissues, caused by heat, electricity, chemicals, friction, or ionizing radiation (such as sunburn, caused by ultraviolet radiation). Most burns are due to heat from hot fluids (called scalding), soli ...

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

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

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 pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(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 transplant Skin grafting, a type of graft surgery, involves the transplantation of skin without a defined circulation. The transplanted tissue is called a skin graft. Surgeons may use skin grafting to treat: * extensive wounding or trauma * burns * a ...

s (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 ...

. The concentrate is solved in a sterile gel 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 (also in liquid form) that is used as a lubricant and for other applications * Liquid paraffin (drug), a very highly refined mineral oil used in cosmetics and for med ...

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

Contraindications and adverse effects

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 wi ...

. The most common side-effects are

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

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

and

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

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, ventricular fibrillation, and wide complex tachycardia, atrial fibrillation, and paroxys ...

chloroquine Chloroquine is an antiparasitic medication that treats malaria. It works by increasing the levels of heme in the blood, a substance toxic to the malarial parasite. This kills the parasite and stops the infection from spreading. Certain types ...

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...

, and

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

. 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 ...

as a

gelling agent In polymer chemistry, gelation (gel transition) is the formation of a gel from a system with polymers. Branched polymers can form Cross-link, links between the chains, which lead to progressively larger polymers. As the linking continues, larger ...

, and a

disodium hydrogen phosphate Disodium phosphate (DSP), or disodium hydrogen phosphate, or sodium phosphate dibasic, is an inorganic compound with the chemical formula . It is one of several sodium phosphates. The salt is known in anhydrous form as well as hydrates , where ' ...

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

buffer Buffer may refer to: Science * Buffer gas, an inert or nonflammable gas * Buffer solution, a solution used to prevent changes in pH * Lysis buffer, in cell biology * Metal ion buffer * Mineral redox buffer, in geology Technology and engineeri ...

References

{{Authority control Preparations for treatment of wounds and ulcers Hydrolases Orphan drugs