Published: 2022-08-29

Management of post-operative wound in dental surgeries using proteolytic enzyme-flavonoid combination of trypsin, bromelain and rutoside: a single-centre experience

Shashank Tiwari, Bhushan M. Khemnar, James John


Background: Appropriate surgical wound management is required to prevent post-operative complications, including delayed wound-healing which may result in increased hospital stay. The present study aimed to evaluate the efficacy and safety of oral administration of a fixed dose combination of trypsin-bromelain-rutoside in the post-operative management after dental surgeries.

Methods: The study was a prospective, observational data collection exercise. Hundred subjects undergoing dental surgeries, who were administered trypsin-bromelain-rutoside combination, were observed over a period of 8 days post-surgery. Verbal rating scales were used for grading the pain intensity and extent of swelling, while a 5-point Likert scale was used to evaluate patient- and investigator-reported global assessment of improvement in pain and swelling. Scores at day 3 and day 8 were analysed using paired t test.

Results: At day 3 and day 8, the mean scores of pain and swelling were significantly reduced from baseline (all p<0.0001). By day 8, 100% of the patients achieved complete resolution of pain, while mild swelling was reported in only 2 patients. At day 3, 95% patients reported good/ very good global improvement in pain and swelling; while at day 8, 100% reported good/ very good improvement. No adverse event was reported in any of the patients.

Conclusions: The study results demonstrate that treatment with trypsin-bromelain-rutoside combination led to significant improvement in the post-operative pain and swelling. The use of this combination is useful for wound recovery and reducing the need for other analgesic and anti-inflammatory drugs.


Dental surgery, Enzymes, Inflammation, Pain, Swelling

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Daftary G, Shah A, Divekar G, John J, Patil N, Khemnar B. Systemic therapy with bromelain- trypsin-rutoside combination in inflammation: A narrative review of the pharmacodynamics. Natl J Physiol Pharm Pharmacol. 2022;12(11):1.

Kerkhoffs GM, Struijs PA, De Wit C, Rahlfs VW, Zwipp H, Van Dijk CN. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes. Br J Sports Med. 2004;38:431-5.

Singer F, Singer C, Oberleitner H. Phlogenzym® versus diclofenac in the treatment of activated osteoarthritis of the knee. A double-blind prospective randomized study. Int J Immunother. 2001;17:135-42.

Klein G, Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes. Clin Drug Investig. 2000;19:15-23.

Akhtar NM, Naseer R, Farooqi AZ, Aziz W, Nazir M. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee a double-blind prospective randomized study. Clin Rheumatol. 2004;23:410-5.

Tilwe G, Beria S, Turakhia N, Daftary G, Schiess W. Efficacy and tolerability of oral enzyme therapy as compared to diclofenac in active osteoarthrosis of knee joint: An open randomized controlled clinical trial. J Assoc Physicians India. 2001;49:617-21.

Klein G, Kullich W, Schnitker J, Schwann H. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006;24:25.

Nanda MS, Kaur M. Role of oral enzymes in post-operative septoplasty cases. Indian J Otolaryngol Head Neck Surg. 2019;71(3):1663-7.

Kamenicek V, Holan P, Franĕk P. Systemic enzyme therapy in the treatment and prevention of post-traumatic and postoperative swelling. Acta Chir Orthop Traumatol Cech. 2001;68:45-9.

Singh T, More V, Fatima U, Karpe T, Aleem MA, Prameela J. Effect of proteolytic enzyme bromelain on pain and swelling after removal of third molars. J Int Soc Prev Community Dent. 2016;6:S197.

Dockery GL, Crawford ME. Lower extremity soft tissue and cutaneous plastic surgery. Elsevier Health Sci. 2012.

Hess CT. Checklist for factors affecting wound healing. Adv Skin Wound Care. 2011;24(4):192.

Conaghan P. A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity. Rheumatol Int. 2011;32(6):1491-502.

Marcum Z, Hanlon J. Recognizing the risks of chronic nonsteroidal anti-inflammatory drug use in older adults. Ann Longterm Care. 2010;18(9):24-7.

Anderson K, Hamm RL. Factors that impair wound healing. J Am Coll Clin Wound Spec. 2012;4(4):84-91.

Fowler C. Do nonsteroidal anti-inflammatory drugs impair tissue healing? JAAPA. 2018;31(8):1-5.

Hotz G, Frank T, Zöller J, Wiebelt H. Antiphlogistic effect of bromelaine following third molar removal. Deutsche Zahnarztliche Zeitschrift. 1989;44(11):830-2.

Ordesi P, Pisoni L, Nannei P, Macchi M, Borloni R, Siervo S. Therapeutic efficacy of bromelain in impacted third molar surgery: a randomized controlled clinical study. Quintessence Int. 2014;45(8).

Singh T, More V, Fatima U, Karpe T, Aleem MA, Prameela J. Effect of proteolytic enzyme bromelain on pain and swelling after removal of third molars. J Int Soc Prevent Communit Dent. 2016;6(3):S197.

María C, Yáñez-Vico RM, Batista-Cruzado A, Heurtebise-Saavedra JM, Castillo-de Oyagüe R, Torres-Lagares D. Prospective double-blind clinical trial evaluating the effectiveness of Bromelain in the third molar extraction postoperative period. Medicina oral, patologia oral y cirugia buccal. 2014;19(2):e157.

Shetty V, Mohan A. A prospective, randomized, double-blind, placebo-controlled clinical trial comparing the efficacy of systemic enzyme therapy for edema control in orthognathic surgery using ultrasound scan to measure facial swelling. J Oral Maxillofac Surg. 2013;71(7):1261-7.

Inchingolo F, Tatullo M, Marrelli M, Inchingolo AM, Picciariello V, Inchingolo AD et al. Clinical trial with bromelain in third molar exodontia. Eur Rev Med Pharmacol Sci. 2010;14(9):771-4.

Majid OW, Al-Mashhadani BA. Perioperative bromelain reduces pain and swelling and improves quality of life measures after mandibular third molar surgery: a randomized, double-blind, placebo-controlled clinical trial. J Oral Maxillofac Surg. 2014;72(6):1043-8.

Navrátil L, Navrátilová B, Knížek J, Erösová Z, Fikáčková H, Kymplová J. Possibilities of current use of non-invasive laser therapy and systemic enzymotherapy in stomatology. J Appl Biomed. 2003;1(1):13-9.

Ghensi P, Cucchi A, Creminelli L, Tomasi C, Zavan B, Maiorana C. Effect of oral administration of bromelain on postoperative discomfort after third molar surgery. J Craniofac Surg. 2017;28(2):e191-7.

Bakhshi GD, Tiwari S, Prajapati RK, Rudrappa GH, Uppin MI, Vinchhi PJ et al. Systemic Enzyme Therapy with Trypsin-Bromelain-Rutoside combination to counter post-operative wound inflammation-a randomized active-controlled multi-centre trial. Eur J Pharm Med Res. 2019;6(8):493-500.