Serrapeptase: Silkworm Enzyme

Serrapeptase is an enzyme originally derived from the silkworm that digests non-living tissue, including blood clots, cysts, scar tissue, arterial plaque and reduces inflammation.

Serrapeptase offers a viable alternative to salicylates (such as aspirin), ibuprofen, and NSAIDS as well as steroids—a boon for those suffering with rheumatoid arthritis and a wide array of other autoimmune diseases that affect the inflammatory response, including ulcerative colitis, psoriasis, uveitis, allergies.

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While antiinflammatory drugs may offer temporary, symptomatic relief from pain, swelling and inflammation, they may also be immunosuppressive and known to hold dangerous side effects. Serrapeptase, on the other hand, eases pain and swelling with no inhibitory effects on prostaglandins and no gastrointestinal side effects. The immunologically active enzyme is completely bound to the alpha 2 macroglobulin in biological fluids.

The physiologic agent is isolated from the microorganism Serratia E15, an enzyme naturally present in the silkworm intestine which allows the emerging moth to dissolve its cocoon. Clinical use of serrapeptase as an antiinflammatory in Europe and Asia spans over twenty five years. Treatment includes chronic sinusitis, elimination of bronchopulmonary secretions (the enzyme breaks down protein fibers, allowing mucous to thin), sprains and torn ligaments, and other traumatic injuries, edema, as well as postoperative inflammation.

Studying postoperative swelling and pain reduction of the upper ankle joint, a test was carried out in 3 randomized groups of 66 patients, each with fresh rupture of the lateral ligament treated surgically between December 1986 and April 1987. The group receiving Serrapeptase saw a 50% decrease in swelling on the third postoperative day. Decreased pain, for the most part, correlated with reduction in swelling. The Serrapeptase group became rapidly pain-free. The two control groups, using traditional elevation of the leg, bed rest, with and without applications of ice, had no reduction in swelling at that time. (Esch PM, Gerngross H, Fabian A, Fortachr Med,107(4):67.8, 71-2 1989 Feb 10)

Another multi-center, double-blind, placebo-controlled trial was carried out to investigate the clinical efficacy of Serrapeptase in 174 patients who underwent Caldwell-Luc antrotomy for chronic empyema. Eighty-eight patients received 10 mg Serrapeptase 3 times the day before surgery, once the night of the operation and 3 times daily for 5 days after surgery; the other 86 received a placebo. 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 surgery up to the 5th day. Maximal buccal swelling throughout all the postoperative points of observation was also significantly smaller in size in the Serrapeptase group. No side effects were reported. (Tachibana M, Mizukosi 0, Harada Y, Kawamoto K, Nakai Y. Source: Pharmathera-peutica, 3(8):526-30 1984).

Additionally, Serrapeptase in a 70 patient, double-blind controlled trial treating breast engorgement saw Serrapeptase improve breast pain and swelling in significant numbers of the treatment group with no adverse reactions. (Kee WH, Tan SL; Lee V, Salmon YM .Singapore Med J, 30(I) :48-54 1989 Feb)

Researchers in Germany have used Serrapeptase to treat atherosclerosis since serrapeptase helps to digest atherosclerotic plaque without harming healthy cells lining the arterial wall. The hardened, narrow arterial wall is considered the cumulative result of microscopic trauma with inflammation occurring in the presence of oxidized lipids—serrapeptase works on both inflammation as well as dissolving the avital plaque. Unlike cholesterol-blocking drugs, serrapeptase clears the avital tissue from the arterial wall without interfering with cholesterol synthesis. In fact, when taking serrapeptase, cholesterol levels may rise as it is dissolved from the arteries to be eliminated from the body (cholesterol in its pure state is an antioxidant and a necessary component of steroidal hormones and the major organ systems in the body).

Medications blocking cholesterol biosynthesis hold the threat of liver, eye, lung and other soft tissue damage. While studies with Serrapeptase in the treatment of coronary artery disease are relatively new; some literature reports Serrapeptase as being superior to, and faster than, chelation.

The late German physician Dr. Hans Nieper used serrapeptase to treat arterial blockage in his coronary patients, reporting that serrapeptase also dissolves blood clots, and causes varicose veins to shrink or diminish.  A US physician prescribing Serrapeptase told of a woman scheduled for hand amputation and a man scheduled for bypass surgery; both recovered without surgery after treatment with serrapeptase.

In addition, Serrapeptase  has been used for fibrocystic breast disease and carpal tunnel syndrome.

Serrapeptase is also used to facilitate the therapeutic effect of antibiotics in the treatment of infection. In urology serrapeptase has been successfully employed to treat cystitis and epididymitis.

Serrapeptase references:

1. Kee WH, Tan SL, Lee V, Salmon YM. The treatment of breast engorgement with Serrapeptase (Danzen): a randomized double-blind controlled trial. Singapore Med J. 1989;30(1):48-54.

2. Mizukoshi, D. et al. A double-blind clinical study of serrapeptase in the treatment of chronic sinusitis. Igaku Ayrni 109:50-62.1979.

3. Carratu, L. et al. Physio-chemical and rheological research on mucolytic activity of serrapeptase in chronic broncho-pneumopathies. Curr.Ther. Res. 28(6):937-951. 1980.

4. Braga, P.C. et al. Effects of serrapeptase on muco-ciliary clearance in patients with chronic bronchitis. Curr. Ther. Res. 29(5):738-744,1981.

5. Mazzone A, et al. Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. J Int Med Res. 1990; 18(5):379-88.

6. Conticello, S. et al. La serrapeptase in ORL Nuova Clin. ORL 31:15-20,1979.

7. Pallotti, S. et al. Valutazu-one della'attivita fibrinolytica della serrapeptase. Farmaci 3:163-173,1982.

8. Kakinumu, A. et al. Regression of fibrinolysis in scalded rats by administration of serrapeptase. Biochem. Pharmacol. 31:2861-2866,1982.

9. Marly, M. Enzymotherapie anti-inflammatoire a l'aide de la serrapeptase: resultats cliniques en traumatologie et en ORL. C RTherapeut. 3:9-19,1985.

10. Odagiri, J. et al. Clinical applications of serrapeptase in sinusitis. Med. Consult. New Remedy 6:201-209, 1979.

11. Yamazaki, J. et al. Anti-inflammatory activity of TSP, a protease produced by a strain of Serratia. Folia Pharmacol. Japon. 6^302-314,1967.

12. Elies, W. et al. Akute und subakute Entzundungen der Nassenbenholen. Z. Allmeinmed. 4:92-95, 1987.

13. Harada, Y. Clinical efficacy of serrapeptase on buccal swelling after radical operation for chronic sinusitis. Igaku Ayumi 123:768-778.1982.

14. Matsudo, A. et at. Effect of serrapeptase (Danzen) on inflammatory edema following operation for thyropid disease. Med. Consult. New Remedy 18:171-175, 1981.

15. Perna, L. Osservazioni cliniche sul trattamento in doppio cieco con Serratio peptidasi, nella rinite perenne nella rinitie cronica riacutizzata con sinusopatia. nella bronchite cronica riacutizzata. Riv. Pat. Clin.Tuberc. Penumol. 56:509-516,1985. 

16. Fujitani, T. et al. Effect of anti-inflammatory agent on transfer of antibiotics to the maxillary sinus mucosa in chronic sinusitis. Otorhinolaryngol. Clin. North Am. 66:557-565. 1976.

17. Tago. T. and Mitsui, S. Effects of serrapeptase in dissolution of sputum, especially in patients with bronchial asthma. Jap. Clin. Exp. Med. 49:222-228, 1972.

18. Tomoda, K. and Miyatam K. Some information on the composition of tracheal secretions before and after the administration of serrapeptase. Exper. Ther. 477:9-16, 1972.

19. Kase Y, et al. A new method for evaluating mucolytic expectorant activity and its application to two proteolytic enzymes, serratiopeptidase and seaprose. Arznelrnitteltorachung. 1982; 32:374-378.

20. Marriott, C. Modification of the rheoloaical properties of mucus by drugs. Adv. Exp. Med. Biol. 144^75-84, 1982.

21. Majima. Y. et al. Effects of orally administered drugs on dynamic viscoelasticity of human nasal mucus. Am. Rev. Respir. Dis. 141:79-83.1990.

22. Miyata, K. Intestinal absorption of serrapeptase. J ApplBiochem. 1980:2:111-16.

23. Aso T. et al. Breast engorgement and its treatment: Clinical effects of Danzen (serrapeptase) an anti-inflammatory enzyme preparation. The world of Obstetrics and Gynecology (Japanese). 1981:33:371-9.

24. Esch PM, Gemgross H. Fabian A. Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase-a prospective study (German). FortschrMed. 1989; 107(4):67-8, 71-2.

25. Majima Y, Inagaki M, Hirata K. Takeuchi K, Morishita A, Sakakura Y. The effect of an orally administered proteolytic enzyme on the elasticity and viscosity of nasal mucus. Arch Otorhinolaryngol. 1988;244(6):355-9.

26. Selan L, Berlutti F, Passariello C, Comodi-Ballanti MR, Thaller MC. Proteolytic enzymes: a new treatment strategy for prosthetic infections? Antimicrob Agents Chemother. 1993; 37(12):2618-21.

27. Koyama A, Mori J, Tokuda H, Waku M, Anno H, Katayama T, Murakami K, Komatsu H, Hirata M, Arai T, et al. Augmentation by serrapeptase of tissue permeation by cefotiam (Japanese). Jpn JAntibiot. 1986; 39(3):761-71.


A preliminary trial of serrapeptase 
in patients with carpal tunnel syndrome.

Panagariya A, Sharma AK

Dept. of Neurology,

SMS Medical College and Hospital, Jaipur, India
J Assoc Physicians India 1999 Dec;47(12):1170-2

OBJECTIVES: This study was planned to assess the response of serrapeptase in patients with carpal tunnel syndrome (CTS). 

METHODS: Twenty patients with CTS were evaluated clinically. After baseline electrophysiological studies, these patients were given serrapetase10 mg twice daily with initial short course of nimesulide.  Clinical and electrophysiological reassessment was done after 6 weeks. 

RESULTS: Mean age was 43.9 years with male to female ratio of 1:2.33. Sixty five percent cases showed significant clinical improvement which was supported by significant improvement in electrophysiological parameters. Recurrence was reported in four cases. No significant side effect was observed. 

CONCLUSIONS: serrapeptase therapy may proved to be a useful alternative mode of conservative treatment.  Larger study may be further helpful to establish the role of serrapeptase in CTS.


Proteolytic enzymes: a new treatment strategy for prosthetic infections?

by Selan L, Berlutti F, Passariello C, Comodi-Ballanti MR, Thaller MC

Istituto di Microbiologia, Facolta di Farmacia, Universita La Sapienza, Rome, Italy.
Antimicrob Agents Chemother 1993 Dec;37(12):2618-21

Among the different mechanisms of bacterial resistance to antimicrobial agents that have been studied, biofilm formation is one of the most widespread.  This mechanism is frequently the cause of failure in the treatment of prosthetic device infections, and several attempts have been made to develop molecules and protocols that are able to inhibit biofilm-embedded bacteria.  We present data suggesting the possibility that proteolytic enzymes could significantly enhance the activities of antibiotics against biofilms.  Antibiotic susceptibility tests on both planktonic and sessile cultures, studies on the dynamics of colonization of 10 biofilm-forming isolates, and then bioluminescence and scanning electron microscopy under seven different experimental conditions showed that serrapetase greatly enhances the activity of ofloxacin on sessile cultures and can inhibit biofilm formation.


A New Method for Evaluating Mucolytic Expectorant Activity and its Application

II. Application to two proteolytic enzymes, serrapeptase and seaprose*

By Y. Kase, H. Seo, Y. Oyama, M. Sakata, K. Tomoda, K. Takahama, T. Hitoshi, Y. Okano, and T. Miyata

Arzneim.-Forsch. / Drug Res. 32 (1), Nr. 4 (1982)

From the Department of Chemico-Pharmacology. Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto (Japan)

Summary: Using our new method described in a preceding paper, in vivo effects of two proteolytic enzymes such as serrapeptase and seaprose (SAP) on sputa collected from bronchitis rabbits were examined. Serrapeptase (20 mg/kg) and SAP (30 mg/kg) significantly reduced the viscosity of sputum (P < 0.05) at the 1-3-h periods and the 4-6-h periods, respectively, after intraduodenal administration. 50 mg/kg of serrapeptase also significantly decreased not only viscosity (P < 0.001) but also amount of freeze-dried substance (P < 0.05) of sputum at the 1-3-h periods, but SAP did not affect the amount of dried substance. Both enzymes significantly increased the volume of sputum, probably as the result of liquefaction. Thus, mucolytic expectorant activity of both enzymes can be demonstrated first by the reduction in viscosity and next by the increase in volume of sputa. However, the decrease in amount of freeze-dried substance is not always in accord with the reduction in viscosity.

Key words: Bromhexine • Bronchitis • Mucolytic expectorants • Proteolytic enzymes • Seaprose • serrapeptase

1. Introduction

In this previous paper [1], we reported a new method which seems to be applicable to examine the in vivo effect of mucolytic expectorants. By the use of this method, the expectorant effect of a drug can be evaluated from the changes in both quantity and quality of sputa, which were quantitatively collected from the rabbits suffering from subacute bronchitis caused by long-term exposure to SO2 gas. The purpose of the present study is to ascertain whether this method is well applicable to the evaluation of mucolytic expectorant effect of the reference drugs as was expected, whose clinical efficacy was already well established. Two proteolytic enzymes, serrapeptase and seaprose, were chosen for such a purpose. Though their chemical properties differ, both enzymes have so far been used as the effective mucolytics in the treatment of various disorders related to viscous sputum or pus, and their efficacies have been war-ranted to be more potent and reliable than those of a-chymotrypsin and others. Therefore, they have widely been used not only in Japan but also in. some other countries. Nevertheless, the pharmacological evidence which sub-stantiates their clinical efficacies, in particular, mucolytic expectorant effect, is insufficient, though they exhibit potent mucolytic activity in in vitro experiments [2, 3]. Bromhexine, a representative of the expectorants, was used as a control drug, because its mechanism of action is quite different from that of proteolytic enzyme, that is, it does not exhibit in vitro mucolytic activity and its main effect is known only by the increase in the volume of respiratory tract fluid (RTF) when it was examined by Perry and Boyd's method [4-7] using normal healthy rabbits. Further pharmacological study, for instance, the acting mechanism of mucolytic expectorant effect of intraduodenally administered enzymes will be described in the subsequent paper.

2. Materials and methods

2.1. Animals and drugs

Male rabbits of New Zealand White-strain, weighing 1.8 to 2.5 kg, were used. Serrapeptase (Danzen*, hereafter abbreviated as SER), a proteolytic enzyme (endopeptidase) prepared from the culture broth of. genus Serratia sp. E-15 (one of enteric bacilli in silkworm) which comes as grayish powder, was provided


Evaluation of Serratia Peptidase in Acute or Chronic Inflammation of Otorhinolaryngology Pathology: a Multicentre, Double-blind, Randomized Trial versus Placebo

A. Mazzone1, M. Catalan2, M. Costanzo3, A. Drusian4, A. Mandol5, S. Russo6, E. Guarini7 and G. Vesperini8 

1 Institute of Clinical Otorhinolaryngology, University of Naples, Naples, Italy; 
2 Ear, Nose and Throat Department, 'Gradenigo' Hospital, Turin, Italy; 
3 Ear, Nose and Throat Department, 'Villa Sofia' Hospital, Palermo, Italy
4 Ear Nose and Throat Department, Treviso Regional Hospital, Treviso, Italy
5 Ear, Nose and Throat Department, 'E. Fornaroli' Hospital, Magenta, Italy
6 Ear, Nose and Throat Department, Lucca Hospital, Lucca, Italy; 
7 Ear, Nose and Throat Department, Civil Hospital, Lecce, Italy; 
8 Ear, Nose and Throat Department, 'Madonna del Soccorso' Hospital, San Benedetto del Tronto, Italy 

The efficacy and tolerability of Serratia peptidase were evaluated in a multi-centre, 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-inflapimatory, anti-edemic and fibrinolytic activity and acts rapidly on localized inflammation. 

Received for publication 2 January 1990; accepted 16 January 1990.

Address for correspondence: A. Mazzone, MD, Institute of Clinical Otorhinolaryngology, University of Naples, Via Pansini 5, 80131 Naples, Italy. 


The use of enzymes with fibrinolytic, I proteolytic and anti-edemic activities has gained increasing support in recent years for the treatment of inflammatory ear, nose and throat (ENT) conditions1. Included among these enzymes is the Serratia peptidase (Danzen® ), a protease obtained from non-pathogenic enterobacteria of the genus Serratia. This proteolytic enzyme, which is available in tablet form to enable it to be absorbed from the intestinal lumen, has been shown lo induce intense fibrinolytic. anti-inflammatory, and anti-edemic activity in a number of tissues and results suggest that its anti-inflammatory activity may be of particular use for the treatment of localized or 'closed' forms of inflammation, such as those frequently found in ENT pathologies.' ^ Another important feature of Serratia peptidase is its effect on pain, the enzyme acting by inhibiting the release of pain-inducing amines, such as bradykinin, from inflammed tissue.1.7

     This peptidase induces fragmentation offibrinose aggregates and reduces the viscosity of exudates,"^ thus facilitating the drainage of these products of the inflammatory response and thereby promoting the tissue repair process, and clinical trials have confirmed that the use of Serratia peptidase resulted in fast resolution of the inflammatory process." ~ '° The aim of the present placebo-controlled multicentre study was to evaluate the efficacy and tolerability of the Serratia peptidase in the treatment of ENT inflammatory conditions.



Patients, who were recruited from ENT clinics throughout Italy, were all suffering from inherent acute or chronic inflammatory conditions. Any patients with serious concomitant conditions, such as severe renal and/or hepatic impairments, or who required additional drugs were excluded from the tnal, as this could interfere with evaluation of the parameters under examination, and the use of steroids, non-steroidal anti-inflammatory drugs and/or anti-inflammatory/analgesic agents was prohibited. Antibiotics were permitted when deemed necessary.


Indistinguishable tablets containing 5 mg Serratia peptidase or a placebo were provided in blister packs and patients were randomly assigned to receive two tablets of either drug, which they were instructed to take three times daily after meals for 7 -8 days.

Evaluation of treatment 
Clinical signs and symptoms were assessed on days 0, 3-4 and 7-8 of treatment on a scale of O-3 (0, absence of the symptoms: 3, maximum severity). Clinical parameters recorded were as follows: pain; quantity of secretion; difficulty in swallowing; nasal obstruction; anosmia; and body temperature. The appearance of the secretion was also recorded on a scale ofO-3 (0, normal; I, mucoid; 2, mucopurulent: 3, purulent). All evaluations were performed by an ENT specialist unaware of the treatment given.  

Evaluation of tolerability 
Tolerability of Serralia peptidase was evaluated on the basis of the presence, absence or severity of side-effects, recorded on the patients' data-collecting forms.

Statistical analysis
All data were analysed by the most appropriate statistical tests (^-test and Student's f-test).  


A total of 193 subjects (96 males, 97 females), aged between 12 and 77 years (mean ± SD 38 ± 15.7 years), with acute or chronic ENT pathologies were recruited to the trial. Of these 193 cases, 97 (43 males, 54 females; mean ± SD 37.3 ± 15.2 years) were placed in group A and 96 (53  


The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trial.

Kee WH, Tan SL, Lee V, Salmon YM.

Singapore Med J 1989 Feb;30(1):48-54

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 (Serrapeptase) 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 (Serrapeptase) 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 (Serrapeptase). Danzen (Serrapeptase) is a safe and effective method for the treatment of breast engorgement.


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.

Pharmatherapeutica 1984;3(8):526-30

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.

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