Serrapeptase

Staphylococcus aureus is a leading cause of healthcare-associated infections. The ability of S. aureus to attach and subsequently accumulate on the surfaces of implanted medical devices and in host tissues makes infections caused by this pathogen difficult to treat. Current treatments have been shown to have limited effect on surface-associated S. aureus, and may be enhanced by the addition of a dispersal agent. This study assessed the enzymatic agents dispersin B, lysostaphin, alpha amylase, V8 protease and serrapeptase, alone and in combination with vancomycin and rifampicin, against biofilms formed by meticillin-resistant and -susceptible strains of S. aureus. The efficacy of both antibiotics was enhanced when combined with any of the dispersal agents. Lysostaphin and serrapeptase were the most effective dispersal agents against all strains tested. These data indicate that combinations of biofilm dispersal agents and antibiotics may extend the therapeutic options for the treatment of S. aureus biofilm-associated infections.

BACKGROUND: Engorgement is the overfilling of breasts with milk, often occurring in the early days postpartum. It results in swollen, hard, painful breasts and may lead to premature cessation of breastfeeding, decreased milk production, cracked nipples and mastitis. Various treatments have been studied but little consistent evidence has been found on effective interventions. OBJECTIVES: To determine the effectiveness and safety of different treatments for engorgement in breastfeeding women. SEARCH METHODS: On 2 October 2019, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. SELECTION CRITERIA: All types of randomised controlled trials and all forms of treatment for breast engorgement were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility, extracted data, conducted 'Risk of bias' assessment and assessed the certainty of evidence using GRADE. MAIN RESULTS: For this udpate, we included 21 studies (2170 women randomised) conducted in a variety of settings. Six studies used individual breasts as the unit of analysis. Trials examined a range of interventions: cabbage leaves, various herbal compresses (ginger, cactus and aloe, hollyhock), massage (manual, electromechanical, Oketani), acupuncture, ultrasound, acupressure, scraping therapy, cold packs, and medical treatments (serrapeptase, protease, oxytocin). Due to heterogeneity, meta-analysis was not possible and data were reported from single trials. Certainty of evidence was downgraded for limitations in study design, imprecision and for inconsistency of effects. We report here findings from key comparisons. Cabbage leaf treatments compared to control For breast pain, cold cabbage leaves may be more effective than routine care (mean difference (MD) -1.03 points on 0-10 visual analogue scale (VAS), 95% confidence intervals (CI) -1.53 to -0.53; 152 women; very low-certainty evidence) or cold gel packs (-0.63 VAS points, 95% CI -1.09 to -0.17; 152 women; very low-certainty evidence), although the evidence is very uncertain. W

3. Cochrane Database Syst Rev. 2016 Jun 28;2016(6):CD006946. doi: 10.1002/14651858.CD006946.pub3. Treatments for breast engorgement during lactation. Mangesi L(1), Zakarija-Grkovic I. Author information: (1)Victoria Hospital, Lovedale Road, Ntselamanzi Location, Alice, South Africa, 5700. Upda

BACKGROUND: Serratiopeptidase is a proteolytic enzyme prescribed in various specialities like surgery, orthopaedics, otorhinolaryngology, gynaecology and dentistry for its anti-inflammatory, anti-edemic and analgesic effects. Some anecdotal reports suggest it to possess anti-atherosclerotic effects also, due to its fibrinolytic and caseinolytic properties. Despite being widely used there are few published studies regarding its efficacy. Thus, evidence regarding its clinical utility is needed. OBJECTIVE: To evaluate the existing evidence regarding efficacy and safety of Serratiopeptidase in clinical practice. EVIDENCE ACQUISITION: A systematic review of all the published articles of Serratiopeptidase using Cochrane Library, PubMed, MEDLINE, Clinical Trials.gov, Google, Dogpile and a manual search of bibliographies was conducted from 1st May 2011 till 15th July 2012. Further emails were sent to all the leading pharmaceuticals who are manufacturing this enzyme preparation for any additional information. All studies related to Serratiopeptidase which included Randomised controlled trials (RCTs), meta-analysis of RCTs, placebo-controlled, single-blind, double-blind, open label, prospective trials as well as preclinical studies were screened and analysed. The scientific credibility of the studies was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading checklist. A total of 24 studies on clinical efficacy of Serratiopeptidase met the inclusion criteria. EVIDENCE SYNTHESIS: Serratiopeptidase search on Cochrane library revealed 16 results among which 9 were Cochrane Central Register of Controlled Trials 2011, issue 4 studies and 7 were Cochrane Central Register of Controlled trials 2012, issue 3 studies. Of these 16 results, 11 were RCTs on efficacy of Serratiopeptidase. PubMed search also revealed 74 results which showed 16 Clinical trials, out of which 9 were RCTs related to Serratiopeptidase. Bandolier online edition (retrieved on 1/5/2011) showed a review 'Serratiopeptidase-finding the evidence' which included 9 RCTs. The evidence supporting the use of Serratiopeptidase as anti-inflammatory and analgesic agent is based on clinical studi

BACKGROUND: Serratiopeptidase for pain, facial swelling and trismus associated with surgical removal of impacted molar is under investigation. However conclusive evidence on the use of serratiopeptidase is lacking. Hence a systematic review and meta-analysis of randomized controlled studies was carried out. METHODS: Electronic databases were searched for eligible studies and necessary data extracted. The data were analysed using non-Cochrane mode in RevMan 5.0. 95% confidence interval (95% CI) was used to represent the deviation from the point estimate. The heterogeneity between the studies was assessed using Forest plot visually, I2 statistics and Chi square test with a statistical P value of <0.10 to indicate statistical significance. Random-effect models were used in case of moderate to severe heterogeneity. RESULTS: Five studies were included for final review. Serratiopeptidase improved trismus better than corticosteroids with the MD, 95% as 4.42 [3.84, 5]. As regards to swelling, no significant difference was observed for serratiopeptidase when compared to corticosteroids. Paucity of studies precludes any conclusion for other outcome measures as well as for other comparator drugs. CONCLUSION: Serratiopeptidase could be used safely and effectively to improve trismus and facial swelling after surgical removal of impacted molar.

BACKGROUND: Serratiopeptidase has been clinically used in controlling surgical and non-surgical inflammatory conditions. This study was conducted to assess the therapeutic effect of Serratiopeptidase in patients undergoing surgical removal of impacted mandibular third molar. METHODS: This randomized clinical trial investigated the efficacy of Serratiopeptidase and Paracetamol after surgical removal of impacted third molar for 5 days (n = 67) as compared with an equivalent dose of placebo and Paracetamol (n = 66). Outcome measures were reported pain, trismus and swelling using Laskin method. All outcome measures were recorded on days 0, 1, 2, 4, and 5 post-surgeries. RESULTS: In this clinical trail 133 patients (mean age 23 years, 54% female) completed the study. Baseline characteristics were comparable across treatment groups. Serratiopeptidase significantly improved trismus compared with control on the 4th day (27.30 ± 7.3 mm and 32.06 ± 7.7 mm, respectively (P < 0.001) Swelling markedly improved, The distance from the lower edge of the earlobe to the midpoint of the symphysis for cases vs control were 111.49 ± 8.1 mm and 115.39 ± 9.9 mm, respectively (P < 0.001). Reported pain, showed no statistical significance difference. CONCLUSION: Serratiopeptidase resulted in better inflammation improvement than placebo over 5 days. Further studies are warranted to assess longer-term and clinical outcomes, as well as safety. CLINICAL RELEVANCE: Serratiopeptidase administered postoperatively helps in improving trismus and swelling after removal of impacted lower third molars. Trial registration The study was registered in ClinicalTrial.gov under the number NCT02493179. Registered 1st of June 2015, https://clinicaltrials.gov/ct2/results?cond=serratiopeptidase .

INTRODUCTION: Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain. METHOD: The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups-oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte®), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)-to evaluate their healing potential in surgical wounds after orthopedic surgery. RESULTS: A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR. CONCLUSION: TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings. TRIAL REGISTRATION: Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

INTRODUCTION: Surgical extraction of lower 3 rd molar is the most frequent intervention in oral surgery. This procedure is often associated with significant post operative swelling that may have both biological and social implications. Various studies have been done using different anti inflammatory drugs to study their impact on inflammation. MATERIAL AND METHODS: This study was conducted on 110 patients who had undergone surgical removal of mandibular third molar. The subjects were divided into two groups by double blind method. In addition to post operative swelling and pain , trismus was evaluated using two different groups of drugs. RESULTS: One group was administered 1 mg of dexamethazone every 8 hours for 3 days post operatively. The other group was administered 10 mg of serratiopaptidase every 8 hours for 3 days post operatively. Swelling, pain and trismus were assessed on the 1 st , 3 rd , 5 th and 7 th post operative days. The results of the studies were statistically analysed. CONCLUSION: The results showed dexamethazone was more effective in reduction of swelling and pain in comparison with serratiopaptidase. Both dexamethazone and serratiopaptidase had the same effect on trismus.

Assessment of postoperative sequelae following the removal of an impacted third molar has been used in clinical pharmacology to evaluate the relative efficacy of various analgesic, anti-inflammatory drugs. This study included 150 patients with impacted lower third molars. They were randomly sorted to receive ibuprofen, paracetamol, betamethasone, serratiopeptidase or placebo. Evaluation of efficacy was made using tape measurement (for swelling), visual analogue scale (for pain evaluation), mouth opening ability and oral temperature. The effect of treatment on hematological parameters, bleeding, wound healing and requirement for rescue medication was also studied. Peak pain scores were observed approximately 5-6 hours after the operation. Betamethasone showed significant analgesic activity from day 1. Ibuprofen and betamethasone were significantly more effective than placebo in reducing swelling. Trismus was least with betamethasone. A significant rise in temperature on the operated side occurred only on day 1 in all the groups. Serratiopeptidase did not showed significant analgesic and anti-inflammatory action. Mild-to-moderate adverse effects were reported.

The aim of this study was to investigate the ability of serrapeptase to reduce postoperative swelling, pain and trismus after third molar surgery. Twenty-four healthy individuals with symmetrically impacted mandibular third molars underwent surgical removal in a prospective, intra-individual, randomized, double-blind, cross-over study. Teeth were removed in 2 sessions by the same surgeon. At each session, one third molar was removed under local anaesthesia via a buccal osteotomy. All patients received a combination of either serrapeptase 5mg or placebo tablets and 1000 mg paracetamol tablets at either the 1st or 2nd operation in accordance with the randomization plan. Cheek thickness, pain and interincisal distance were measured preoperatively, and on the 1st, 2nd, 3rd and 7th postoperative days. Cheek thickness and maximum interincisal distance were measured using calipers. Pain intensity was assessed clinically using a numeric scale. There was a significant reduction in the extent of cheek swelling and pain intensity in the serrapeptase group at the 2nd, 3rd and 7th postoperative days (P<0.05), but no significant difference in mean maximal interincisal distance was found between the 2 groups (P>0.05).

OBJECTIVES: The proteolytic enzyme serrapeptase (SER) is widely used in clinical practice in Japan. We investigated the effect of SER on sputum properties and symptoms in patients with chronic airway diseases. METHODS: This study was an open-labelled trial with a non-treatment control group. Patients were randomly assigned to oral treatment with (n = 15) and without (n = 14) SER 30 mg/day for 4 weeks. Patients collected sputum samples for about 4 h in the morning on the day the trial began and 4 weeks later. We measured the amount of sputum by weighing. Part of each sputum sample was weighed and then completely dried and reweighed. The percentage solid component, viscosity and elasticity of the sputum were measured. Mucociliary transportability index was measured using ciliated bovine trachea ex vivo. Sputum smears were also prepared to count sputum neutrophils. Patients' symptoms were assessed by a questionnaire that used a visual analogue scale. RESULTS: After 4 weeks of SER treatment, sputum weight in the morning, percentage solid component, viscosity and elasticity of sputum, sputum neutrophil count, frequency of coughing and frequency of expectoration significantly decreased. The mean mucociliary transportability index increased from 13.3 +/- 1.8 to 24.4 +/- 2.5 (P = 0.0103). CONCLUSIONS: SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases.

This study was designed to compare the efficacy and safety of seaprose S and serratio-peptidase in the treatment of venous inflammatory disease. Forty patients entered the study (11 males, 29 females), mean age 54.3 years (range 30-77), mean weight 74.8 kg (range 51-96), with superficial thrombophlebitis. The trial was conducted following a controlled, between patients, randomized experimental design. Seaprose S was administered as 30 mg tablets at a daily dosage of 90 mg (one tab t.i.d.), and serratio-peptidase as 5 mg tablets, at a dose of 30 mg per day (two tabs t.i.d.), both orally, for 14 days. Twenty patients received seaprose S and 20 serratio-peptidase. The findings indicate that seaprose S was more effective and better tolerated than serratio-peptidase. Although the group of patients assigned to seaprose S had considerably more severe initial symptoms, by the end of treatment spontaneous pain was reduced 68.7% from the baseline mean score (from 3.2 to 1.0), as compared with a 63.3% reduction in the serratio-peptidase group (from 3.0 to 1.1). Pain on pressure was reduced 61.1% with seaprose S (from 3.6 to 1.4), compared to 57.6% with the reference treatment (from 3.3 to 1.4). Edema was reduced respectively 75% (from 1.6 to 0.4) and 56.2% (from 1.6 to 0.7); erythema diminished 72.4% (from 2.9 to 0.8) and 58.3% (from 2.4 to 1.0); nighttime cramps were 61.1% less (from 1.8 to 0.7) compared with 52.9% (from 1.7 to 0.8); hemorrhagic suffusion was 53.3% less (from 1.5 to 0.7) compared with 41.7% (from 1.2 to 0.7); cutaneous dystrophy was reduced by 11.1% (from 1.8 to 1.6) and 7.7% (from 1.3 to 1.2). At the end of the treatment with seaprose S efficacy was assessed as good or excellent in 85% of the cases, compared with 65% for serratio-peptidase. Seaprose S caused no adverse reactions. During serratio-peptidase treatment one patient reported diarrhea, requiring temporary dosage reduction and specific treatment. It can thus be confirmed that seaprose S was effective and well tolerated in patients with inflammatory venous diseases.

The efficacy and tolerability of Serratia peptidase were evaluated in a multicentre, double-blind, placebo-controlled study of 193 subjects suffering from acute or chronic ear, nose or throat disorders. Treatment lasted 7-8 days, with the drug or placebo being administered at a rate of two tablets three times a day. After 3-4 days' treatment, significant symptom regression was observed in peptidase-treated patients. There was also a significant reduction in symptoms after 7-8 days for patients in both treatment groups but the response was more marked in those patients receiving the active drug. Statistical comparison between the two groups confirmed the greater efficacy and rapid action of the peptidase against all the symptoms examined at both stages. Tolerance was found to be very good and similar for both groups. It is concluded that Serratia peptidase has anti-inflammatory, anti-oedemic and fibrinolytic activity and acts rapidly on localized inflammation.

11. Fortschr Med. 1989 Feb 10;107(4):67-8, 71-2. [Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase-- a prospective study]. [Article in German] Esch PM, Gerngross H, Fabian A. Using a quantitative standardized procedure, the swelling of the ankle produced by supination trauma was measured. In the 66 patients with fresh rupture of the lateral ligament treated surgically at our Department between December 1986 and April 1987, a prospective study of the effect of serrapeptase (Aniflazym) on post-operative swelling and pain was carried out in 3 randomized groups of patients. In the group receiving the test substance, the swelling had decreased by 50% on the third post-operative day, while in the other two control groups (elevation of the leg, bed rest, with and without the application of ice) no reduction in swelling had occurred at that time. The difference is statistically significant (p = 0.013). Decreasing pain correlated for the most part with the reduction in swelling. Thus, the patients receiving the test substance more rapidly became pain-free than did the control groups. On the basis of these results, serrapeptase would appear to be an effective preparation for the post-operative reduction of swelling, in comparison with the classical conservative measures, for example, the application of ice.

12. Singapore Med J. 1989 Feb;30(1):48-54. The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trial. Kee WH, Tan SL, Lee V, Salmon YM. We evaluated an anti-inflammatory enzyme drug Danzen (Serrapeptase: Takeda Chemical Industries, Ltd.) on 70 patients complaining of breast engorgement. These patients were randomly divided into 2 groups, a treatment group and a placebo group. A single observer, unaware of the group the patients were in, assessed the severity of each of the symptoms and signs of breast engorgement before treatment was commenced, and daily for 3 days, during which therapy was administered. Danzen was noted to be superior to placebo for improvement of breast pain, breast swelling and induration and while 85.7% of the patients receiving Danzen had "Moderate to Marked" improvement, only 60.0% of the patients receiving placebo had a similar degree of improvement. "Marked" improvement was found in 22.9% of the treatment group and 2.9% of the placebo group. These differences were statistically significant (P less than 0.05). No adverse reactions were reported with the use of Danzen. Danzen is a safe and effective method for the treatment of breast engorgement.

13. Pharmatherapeutica. 1984;3(8):526-30. A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling. Tachibana M, Mizukoshi O, Harada Y, Kawamoto K, Nakai Y. A multi-centre, double-blind, placebo-controlled trial was carried out to investigate the clinical efficacy of the anti-inflammatory enzyme serrapeptase in a total of 174 patients who underwent Caldwell-Luc antrotomy for chronic empyema. Eighty-eight patients received 10 mg serrapeptase 3 times on the day before operation, once on the night of the operation and 3 times daily for 5 days after operation; the other 86 received placebo. Changes in buccal swelling after operation were observed as a parameter of the response to treatment. The degree of swelling in the serrapeptase-treated patients was significantly less than that in the placebo-treated patients at every point of observation after operation up to the 5th day (p less than 0.01 to p less than 0.05). Maximal swelling throughout all the post-operative points of observation was also significantly smaller in size in the serrapeptase-treated group than in the placebo-treated group. No side-effects were reported.

14. Biorheology. 1983;20(5):677-83. doi: 10.3233/bir-1983-20523. Effect of expectorants on relaxation behavior of sputum viscoelasticity in vivo. Shimura S, Okubo T, Maeda S, Aoki T, Tomioka M, Shindo Y, Takishima T, Umeya K. We studied the effects of expectorants (mucolytic agents) in vivo on the relaxation behavior of sputum viscoelasticity. Seven female and thirty-three male patients (56.8 +/- 19.3 yrs, range: 21 to 82 years old) with a chronic pulmonary disease except bronchial asthma were studied. They were randomly put into the control group or a group which would be given oral treatments with an expectorant for a week after a one week washout period. The groups were as follows: Group I (n = 8), control; Group II (n = 7), Bromhexine hydrochloride 24 mg per day; Group III (n = 10), Ambroxol 90 mg per day; Group IV (n = 9) alpha - Chymotrypsin buccle 100 ch.u. per day; Group V (n = 6), Serratiopeptidase 30 mg per day. In Groups IV & V, frequency dependence of sputum viscoelasticity at the range of omega = 10(-3) to 10(0) rad.sec-1 were clearly changed after the treatments, and the magnitude of the relaxation and its main relaxation time were significantly increased. On the other hand, in Groups I, II & III, no significant changes of the frequency dependences were observed. These findings suggest that proteolytic enzymes administered orally work on the molecular structure of sputum, and break down their linkages between subunits of the structure.