|
Information
about Serrapeptase:
Clinical
Studies with Serrapeptase:
Serrapeptase
- Insect-Derived Enzyme Fights Inflammation
Our bodies have a love-hate
relationship with inflammation. On the one hand, inflammation is a natural response,
necessary to protect the body from invading organisms. On the other hand, inflammation
can limit joint function, and destroy bone, cartilage and other articular structures.
An elusive goal of scientists and physicians has been to find
a side-effect-free substance to reduce the pain and inflammation associated with
fibrocystic breast disease, rheumatoid arthritis, idiopathic edema, carpal tunnel
syndrome and post-operative swelling. It appears that the search may be nearing
an end, thanks to an enzyme Serrapeptase produced by the larval form of the silk
moth.
Serrapeptase
is an enzyme that is produced in the intestines of silk worms to break down cocoon
walls. This enzyme is proving to be a superior alternative to the non-steroidal
anti-inflammatory agents (NSAIDs) traditionally used to treat rheumatoid arthritis
and osteoarthritis. Its uses
have also been extended to the treatment of chronic sinusitis and postoperative
inflammation, and some researchers believe the substance can play an important
role in arterial plaque prevention and removal.
Harmful
Effects of NSAIDs
NSAIDs, which include aspirin, ibuprofen, salicylates, and
naproxen, are among the most commonly prescribed medications for inflammation
resulting from rheumatoid arthritis, joint conditions, osteoarthritis, gouty
arthritis, joint and muscle discomfort associated with systemic lupus erythematosus,
and other musculoskeletal disorders.(1) In some cases, this overeliance on NSAIDs
has proved deadly. Annually, 76,000 people are hospitalized from NSAID-induced
gastrointestinal complications. The American Medical Association estimates that
from 50-80 percent of those hospitalized for gastrointestinal bleeding are taking
some form of NSAIDs. At this stage in the medication-induced bleeding, there
is a ten percent chance of fatality.(2)
NSAIDs lethal effects result from the
inhibition of the biosynthesis of prostaglandins. NSAIDs block cyclo-oxygenase,
the enzyme responsible for catalyzing the reactions of arachidonic acid to endoperoxide
compounds. This process
results in the inhibition of gastric prostaglandin E, a hormone which protects
the lining of the stomach from acid. After prolonged and frequent ingestion of
NSAIDs, the stomach remains defenseless and at increased susceptibility to ulcers.(3-4)
If an ulcer erodes into a blood vessel, bleeding results. An ulcer
can destroy part of the stomach and duodenal walls, leaving a gap that requires
immediate surgery.
In one study, 1,826 osteoarthritis or
rheumatoid arthritis patients who had been taking NSAIDs for six months or more
and who had been unable to tolerate continuous NSAID use because of adverse gastrointestinal
symptoms were examined endoscopically for gastroduodenal lesions and ulcers.
Clinically significant gastroduodenal lesions were found in 37.1 percent of the
patients. Of those, 24 percent had ulcers. The prevalence of gastroduodenal ulcers
increased with age, duration of osteoarthritis, and duration of current NSAID
use. The
authors of the study wrote: "These results provide further endoscopic
confirmation of the association between NSAID use and gastroduodenal lesions
and ulcers and support the contention that safer treatment alternatives to conventional
NSAIDs are required."(5)
That advice is particularly wise in light of the
other effects NSAIDs have on the gastrointestinal tract. In one group
of 312 NSAID takers, 20 percent had levels of inflammation comparable to that
previously reported in patients with inflammatory bowel disease.(6) Besides damaging
the gastrointestinal tract, NSAIDs also interfere with and suppress bone repair
and remodeling. One paper
presented data obtained over a 12-year period, and outlined the effects of NSAIDs
on the matrix synthesis and turnover in 650 arthritic and 180 non-arthritic human
cartilages. The study showed that one category of NSAIDs that includes Naproxen,
ibuprofen, indomethacin, and nimezulide significantly inhibited matrix synthesis
and had toxic effects on cartilage metabolism.(7) Thus, it
appears that the drugs many patients take to relieve their arthritic pains actually
contributes to further destruction of their joints!
Additionally, NSAIDs have
been shown to interfere with patients' sleep patterns. One study
of 37 male and female subjects at the sleep laboratory at Bowling Green State
University in Ohio demonstrated that aspirin and ibuprofen, in comparison to
a placebo, increased the number of awakenings and the percentage of time spent
awake. The drugs also decreased sleep efficiency, and delayed the onset of the
deeper stages of sleep.(8)
Even insulin
secretion is affected by NSAIDs. Neonatal rat pancreatic cells were examined
partly to determine the effects of insulin secretion caused by prostaglandin
E (PGE) and drugs that inhibit its synthesis-i.e. NSAIDs. Two NSAIDs, sodium
salicylate (aspirin) and ibuprofen, at drug concentrations similar to those achieved
therapeutically in humans, inhibited PGE synthesis up to 70-80 percent. Augmented
insulin secretion accompanied the PGE inhibition. Both drugs shifted the glucose-insulin
response curves to the left at low glucose concentrations and augmented maximal
insulin release at high glucose concentrations.(9)
Other NSAID-induced side effects
include kidney damage, blood dyscrasias and cardiovascular effects, complication
of antihypertensive therapies involving diuretics or beta-adrenoceptor blockade,
and adverse effects in patients with heart failure and cirrhosis.(10) In one
instance, a woman treated for rheumatoid arthritis with the NSAID sulindac developed
gallstones composed of sulindac metabolites.(11)
Interestingly,
NSAIDs have also induced adverse psychiatric reactions. Five psychiatric outpatients-two
with major depressive disorders, one with a bipolar disorder, one with a schizophrenic
disorder and one with an anxiety disorder-were treated with NSAIDs due to rheumatoid
arthritis, osteoarthritis, or other painful neuromuscular conditions. All five
patients developed moderate to severe depression. Three patients became paranoid,
and four either attempted or considered suicide. These psychiatric symptoms disappeared
once the patients stopped taking NSAIDs. When the patients re-started the drugs,
the symptoms returned.(12)
NSAIDs
Roulette
Due to the
detrimental effects of NSAIDs on the body, most physicians resort to a game of "NSAID musical-chairs," taking
a patient off one NSAID as soon as side effects become evident or the drug stops
working, then treating the patient with another of the 10 most widely prescribed
propionic acid-derived NSAIDs.
To provide
a more consistent form of treatment, researchers have long searched for a side-effect
free anti-inflammatory agent. Researchers have recently focused on selective
cyclo-oxygenase (COX-2) inhibitors, more precise versions of NSAIDs. Whereas
previous NSAIDs reduced inflammation by inhibiting all cyclo-oxygenase activity,
these new selective COX-2 inhibitors differentiate between the two forms of COX:
COX-1 appears to regulate many normal physiologic functions and COX-2 mediates
the inflammatory response. These selective
inhibitors are believed to reduce inflammation without influencing normal physiologic
functions by inhibiting only COX-2. By leaving COX-1 alone, the selective inhibitors
result in fewer gastrointestinal side effects.
At first glance, these COX-2 inhibitors
look like the solution to NSAID complications. Upon further inspection, however,
celecoxib, a highly selective COX-2 inhibitor, can cause headaches, change in
bowel habits, abdominal discomfort and dizziness in osteoarthritis patients.
Fewer adverse effects are reported in rheumatoid arthritis patients, but because
the drug is metabolized in the liver by cytochrome P-450 isozyme CYP2C9, serious
drug interactions are possible. Fung and colleagues pointed out that more clinical
studies are needed before the selective COX-2 inhibitors are put into widespread
use.(13)
Another new drug, Enbrel, initially showed promise of treating
the pain associated with rheumatoid arthritis. Currently,
however, the FDA is advising physicians about safety concerns of the new drug.
Thirty of the 25,000 patients treated with Enbrel since the drug's approval have
developed serious infections, including sepsis. Several of those patients died
as a result of the infections. Those at greatest risk when taking Enbrel appear
to be patients with a history of chronic or recurrent infections, pre-existing
infections, diabetes, or other conditions making them more susceptible to infection.(14)
The potentially
lethal side effects associated with NSAIDs and other drugs indicate that a superior
anti-inflammatory substance is needed.
Serrapeptase:
A Natural Anti-Inflammatory
Serrapeptase, also known as Serratia peptidase,
is a proteolytic enzyme isolated from the non-pathogenic enterobacteria Serratia
E15. Serrapeptase is found in negligible amounts in the urine, suggesting that it is transported
directly from the intestine into the bloodstream.(15,16)
Clinical
studies show that serrapeptase induces fibrinolytic, anti-inflammatory and anti-edemic
(prevents swelling and fluid retention) activity in a number of tissues, and
that its anti-inflammatory effects are superior to other proteolytic enzymes.(18)
Besides reducing inflammation, one of serrapeptase's most profound benefits is
reduction of pain, due to its ability to block the release of pain-inducing amines
from inflamed tissues.(18) Physicians throughout Europe and Asia have recognized
the anti-inflammatory and pain-blocking benefits of this naturally occurring
substance and are using it in treatment as an alternative to salicylates, ibuprofen
and other NSAIDs.(19)
In Germany
and other European countries, serrapeptase is a common treatment for inflammatory
and traumatic swellings, and much of the research that exists on this substance
is of European origin. One double-blind study was conducted by German researchers
to determine the effect of serrapeptase on post-operative swelling and pain.
This study involved sixty-six patients who were treated surgically for fresh
rupture of the lateral collateral ligament of the knee. On the third post-operative
day, the group receiving serrapeptase exhibited a 50 percent reduction of swelling,
compared to the controls. The patients receiving serrapeptase also became more
rapidly pain-free than the controls, and by the tenth day, the pain had disappeared
completely.(20)
Cystic
Breast Disease
Serrapeptase
has also been used in the successful treatment of fibrocystic breast disease.
In a double-blind study, 70 patients complaining of breast engorgement randomly
were divided into a treatment group and a placebo group. Serrapeptase was superior
to the placebo for improvement of breast pain, breast swelling and induration
(firmness). 85.7 percent of the patients receiving serrapeptase reported moderate
to marked improvement. No adverse reactions to serrapeptase were reported and
the researchers concluded that "serrapeptase is a safe and effective method
for the treatment of breast engorgement."(21,19)
Serrapeptase
and Sinusitis
Due to its inflammatory properties, serrapeptase has been
shown in clinical studies to benefit chronic sinusitis sufferers. In this condition,
the mucus in patients' nasal cavities is thickened and hypersecreted. This thickening
causes mucus to be expelled less frequently. Japanese
researchers evaluated the effects of serratiopeptidase (30 mg/day orally for
four weeks) on the elasticity and viscosity of the nasal mucus in adult patients
with chronic sinusitis. Serratiopeptidase reduced the viscosity of the mucus,
improving the elimination of bronchopulmonary secretions.(23)
Other clinical
trials support serrapeptase's ability to relieve the problems associated with
chronic sinusitis. In one study, 140 patients with acute or chronic ear, nose
and throat pathologies were evaluated with either a placebo or the active serratia
peptidase. Patients
taking the serrapeptase experienced a significant reduction in severity of pain,
amount of secretion, purulence of secretions, difficulty in swallowing, nasal
dysphonia, nasal obstruction, anosmia, and body temperature after three to four
days and at the end of treatment. Patients
suffering from laryngitis, catarrhal rhinopharyngitis and sinusitis who were
treated with serrapeptase experienced a significant and rapid improvement of
symptoms after 3-4 days. Physicians assessed efficacy of treatment as excellent
or good for 97.3 percent of patients treated with serrapeptase compared with
only 21.9 percent of those treated with a placebo.(24)
Respiratory diseases are
characterized by increased production of a more dense mucus modified in viscosity
and elasticity. Traditionally,
in respiratory diseases, muco-active drugs are prescribed to reestablish the
physicochemical characteristics of the mucus in order to restore respiratory
function. Some of these drugs, however, cause a functional depletion of mucus,
whereas Serrapeptase alters the elasticity of mucus without depleting it.(25,10)
A powerful agent by itself, serrapeptase teamed with antibiotics
delivers increased concentrations of the antimicrobial agent to the site of the
infection. Bacteria often endure a process called biofilm formation, which results
in resistance to antimicrobial agents. In an attempt to prevent this bacterial
immunity, researchers have experimented with various means of inhibiting biofilm-embedded
bacteria. Their search
may have ended with serrapeptase. One study conducted by Italian researchers
suggests that proteolytic enzymes could significantly enhance the activities
of antibiotics against biofilms. Antibiotic susceptibility tests showed that
serratiopeptidase greatly enhances the activity of the antibiotic, ofloxacin,
and that it can inhibit biofilm formation.(28)
Another double-blind randomized
study evaluated the effects of administering the antibiotic cephalexin in conjunction
with serrapeptase or a placebo to 93 patients suffering from either perennial
rhinitis, chronic rhinitis with sinusitis or chronic relapsing bronchitis. The
serratia peptidase treated group experienced significant improvement in rhinorrhea,
nasal stuffiness, coryza and improvement of the para-nasal sinus shadows.(24)
Researchers
witnessed equally impressive results in the treatment of infections in lung cancer
patients undergoing thoracotomy. Serrapeptase and cefotiam, an antibiotic with
a broad spectrum of activity against both Gram-positive and Gram-negative microorganisms,
were administered to 35 thoracotomy patients with lung cancer. The patients were
divided into two groups. A single dose of cefotiam was administered to the 17
subjects in Group I. The 18 subjects in Group II received a combination of Cefotiam
and serrapeptase. The level of the antibiotic in the tissues versus the blood
was significantly higher in the serrapeptase group than the single dose group.(22)
Cardiovascular
Implications
Hans A.
Nieper, M.D., an internist from Hannover, Germany, studied the effects of serrapeptase
on plaque accumulations in the arteries. The formation of plaque involves deposits
of fatty substances, cholesterol, cellular waste products, calcium and fibrin
(a clotting material in the blood) on the inner lining of the arteries. Excessive
plaque results in partial or complete blockage of the blood's flow through an
artery, resulting in arteriosclerosis, or hardening of the arteries, and an ensuing
stroke or heart attack. The evidence to support serrapeptase's role in preventing
plaque build-up is anecdotal. Still, further studies are called for in this area
as Nieper's research indicated that the protein-dissolving action of serrapeptase
will gradually break down atherosclerotic plaques.(24)
Conclusion
Regardless
of whether serrapeptase is used for inflammatory diseases or to prevent plaque
build up on the arteries, it is well-tolerated. Due to its lack of side effects
and anti-inflammatory capabilities, serrapeptase is a logical choice to replace
harmful NSAIDs. Thanks to the tiny larvae of the silk moth, researchers have
taken a large step toward finding relief for inflammatory disease sufferers.
References
1.
Raskin JB. Gastrointestinal effects of nonsteroidal anti-inflammatory therapy.
Am J Med. 1999; 106 (5B):3S-12S.
2. No author
listed. Regular Use of Pain Relievers Can Have Dangerous Results. Kaleidoscope
Interactive News, American Medical Association media briefing. July 24, 1997.
3.
Fung HB, Kirschenbaum, HL. Selective cyclooxygenase-2 inhibitors for the treatment
of arthritis. Clin Ther. 1999; 21(7):1131-57.
4. Geis GS.
Update on clinical developments with celecoxib, a new specific COX-2 inhibitor:
what can we expect? Scand J Rheumatol Suppl. 1999; 109:31-7.
5. Cheatum
DE, Arvanitakis C, Gumpel M, Stead H, Geis GS. An endoscopic study of gastroduodenal
lesions induced by nonsteroidal anti-inflammatory drugs. Clin Ther. 1999; 21(6):992-1003.
6.
Tibble JA, Sigthorsson G, Foster R, Scott D, Fagerhol MK, Roseth A, Bjarnason
I. High prevalence of NSAID enteropathy as shown by a simple faecal test. Gut.
1999; 45(3):362-6.
7. Dingle
JT. The effects of NSAID on the matrix of human articular cartilages. Z Rheumatol.
1999; 58(3):125-9.
8. Murphy
PJ, Badia P, Myers BL, Boecker MR, Wright KP Jr. Nonsteroidal anti-inflammatory
drugs affect normal sleep patterns in humans. Physiol Behav. 1994; 55(6):1063-6.
9.
Metz SA, Robertson RP, Fujimoto WY. Inhibition of prostaglandin E synthesis augments
glucose-induced insulin secretion in cultured pancreas. Diabetes. 1981; 30(7):551-7.
10.
Marriott C. Modification in the rheological properties of mucus by drugs. Adv
Exp Med Biol. 1982; 144:75-84.
11. Tokumine
F, Sunagawa T, Shiohira Y, Nakamoto T, Miyazato F, Muto Y. Drug-associated cholelithiasis:
a case of sulindac stone formation and the incorporation of sulindac metabolites
into the gallstones. Am J Gastroenterol. 1999;94(8):2285-8.
12. Jiang
HK, Chang DM. Non-steroidal anti-inflammatory drugs with adverse psychiatric
reactions: five case reports. Clin Rheumatol. 1999;18(4):339-45.
13. Fung
HB, Kirschenbaum, HL. Selective cyclooxygenase-2 inhibitors for the treatment
of arthritis. Clin Ther. 1999; 21(7):1131-57.
14. FDA MedWatch:
The FDA Medical Products Reporting Program. May 12, 1999. FDA Talk Paper.
15.
Moriya N, Nakata M, Nakamura M, Takaoka M, Iwasa S, Kato K, Kakinuma A. Intestinal
absorption of serrapeptase (TSP) in rats. Biotechnol Appl Biochem. 1994; 20(Pt1):101-8.
16.
Miyata, K. Intestinal absorption of Serratia Peptidase. J Appl Biochem. 1980;2:111-16.
17.
Perna L. Osservazionl Clniche sui traitamento in osppio cleco con Serratio peptidasl
nella neifre perenna naila ninite cronica nacutizzata con sinusopattia, nella
bronchia cronica nacutizzata. Rlv Pat Clin Tuberc Penumol. 1985; 56:509-516.
18.
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.
19. Aso T
et al. Breast engorgement and its treatment: Clinical effects of Danzen an anti-inflammatory
enzyme preparation. The world of Obstetrics and Gynecology (Japanese). 1981;
33:371-9.
20. Esch
PM, Gerngross H, Fabian A. Reduction of postoperative swelling. Objective measurement
of swelling of the upper ankle joint in treatment with serrapeptase-a prospective
study (German). Fortschr Med. 1989;107(4):67-8, 71-2.
21. 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.
22.
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 J Antibiot. 1986; 39(3):761-71.
23. 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.
24. Brewer
Science Library website. 1999.
25. Tomoda
K, and Miyatam K. Some information on the composition of trachael secretions
before and after the administration of Danzen. Exper Ther. 1972; 477:9-16.
26.
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.
28. 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.
A preliminary
trial of serrapeptase in patients with carpal tunnel syndrome.
Panagariya A, Sharma AK
Dept. of
Neurology, SMS Medical College and Hospital, Jaipur.
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
o Bronchitis o Mucolytic expectorants o Proteolytic enzymes o Seaprose o 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
1Institute
of Clinical Otorhinolaryngology, University of Naples, Naples, Italy;
2Ear, Nose and Throat Department, 'Gradenigo' Hospital, Turin, Italy;
3Ear, Nose and Throat Department, 'Villa Sofia' Hospital, Palermo, Italy;
4Ear Nose and Throat Department, Treviso Regional Hospital, Treviso, Italy;
5Ear, Nose and Throat Department, 'E. Fornaroli' Hospital, Magenta, Italy;
6Ear, Nose and Throat Department, Lucca Hospital, Lucca, Italy;
7Ear, Nose and Throat Department, Civil Hospital, Lecce, Italy;
8Ear, 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.
INTRODUCTION
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
AND METHODS
Patients
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.
Treatment
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).
RESULTS
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.
|
