An Overview of Miracle Enzyme- Serratiopeptidase

Manju Rawat, SJ Daharwal, Deependra Singh*

Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G.), INDIA-492010

* Corresponding Author E-mail: deependraiop@gmail.com

ABSTRACT

Inflammation and pain is the primary symptom associated with number of diseases/disorders. Search for a safe and

effective  physiological agent  that  offers  anti-inflammatory properties  without  causing  side  effects  of  conventional treatment such as evident in case of NSAIDS and steroids has somewhat ended with the discovery of Serratiopeptidase. It is an acid labile enzyme obtained from silkworms. It has proven its effectiveness in a number of clinical studies against various inflammatory and painful conditions. In this review various aspects of this miracle enzyme has been highlighted together with its pharmacokinetics, pharmacodynamics, adverse effects and clinical uses.

 KEY WORDS              Inflammation; pain; NSAIDS; acid-labile enzyme; debridement; proteolytic enzyme.                                                                                                                                                                           

INTRODUCTION:

Proteolytic enzymes (also known as proteinases or peptidases) are ubiquitous in  nature, being found in animals, plants, bacteria, and fungi. Enzymes are generally   large   globular   proteins   that   range   in molecular weight from about 10,000 to several million. Thousands of different enzymes have been identified, registered, clinically investigated and commercially marketed. Human beings also generate countless peptidases to control virtually every regulatory mechanism in the body to digest food, initiate blood clotting, dissolution of clots, in evoking and quelling of an immune response, and in both promotion and halt of inflammation. These enzymes are highly specific both in  the  reaction  catalyzed  and  in  their  choice  of reactants, which are called substrates. Formation of an enzyme-substrate complex is the first step in enzymatic catalysis. Each of the thousands of known enzymes has a characteristic three-dimensional shape with a specific surface  configuration.  The  unique  configuration  of each enzyme enables it to find the correct substrate from  the  large  number  of  diverse  molecules in  the body. The mechanism of enzyme in each case is its ability  to  cleave  a  protein  target  into  two  or  more pieces,  usually  at  very  specific  cleavage  sites.  The same mechanism makes it possible for peptidases to inactivate HIV, the AIDS-associated virus, by pruning

the viral proteins necessary for infectivity¹.

The proteolytic enzymes in common use today are derived from bacteria, plants, and animal sources^2-3. These are generally utilized for their anti-inflammatory and tissue debriding activity^4-5. Among this category, Serratiopeptidase obtained from Serratia marscens culture is one of the most potent members.

CHRONOLOGICAL OVERVIEW OF ENZYMES AS ANTI-INFLAMMATORY AGENTS

Enzymes were first used as an anti-inflammatory in modern medicine in the 1950s in the United States when intravenous trypsin was found to relieve inflammation due to rheumatoid arthritis, ulcerative colitis, and atypical viral pneumonia as well as post-surgical swelling and bruises caused by sports injuries. Later, intramuscular injections were also studied⁴. In 1957, the Japanese began using serratiopeptidase for inflammation⁶. Then, in the 1960s, researchers in the United States successfully used enterically coated protein enzymes such as trypsin and chymotrypsin or bromelain to administer enzymes orally⁷. In Japan, researchers continued to focus on serratiopeptidase for its anti-inflammatory activity. In the

1980s and early 1990s, Japanese and European research compared several of the protein enzymes and their study indicated that serratiopeptidase was the most effective of all of them in reducing the inflammation response. Serratiopeptidase became widely used in Japan and Europe as the anti-inflammatory and pain treatment of choice².

SERRATIOPEPTIDASE:

Serratiopeptidase is an endopeptidase, having molecular weight of about 60 K Dalton. It is a stronger caseinolytic

Table 1 Clinical significance of serratiopeptidase

S.No	Clinical use	Symptoms	Remarks	Symptoms treated	Effects	Reference
1.	Cystic breast disease	Breast engorgement	More than 88% persons reported               marked improvement	Reduction  in  breast pain,   swelling   and induration	No            adverse reactions reported	Kee    et    al, 1989
2.	Sinusitis /bronchitis	Hypersecretion   of thick mucus	More than 97% persons reported               marked improvement	Reduction     in     the viscosity      of      the mucus improving the elimination             of bronchopulmonary secretions	Effective            in laryngitis, catarrhal rhinopharyngitis and sinusitis	Shimura     et al, 1983
3.	Microbial infections	Biofilm-embedded bacteria	More  than  87%  treated group   reported   marked improvement	Significant improvement in rhinorrhea,        nasal stuffiness,   coryza and paranasal sinus shadows	Effective            in perennial rhinitis, chronic      rhinitis with sinusitis or chronic relapsing bronchitis	Aratani et al, 1980
4.	Carpal    Tunnel syndrome	Musculoligamento us   strain   of   the hand and wrist	Sixty five percent of the patients  showed  clinical improvement.	Improvement in pain and inflammation	No            adverse reactions reported	Panagariya and  Sharma, 1999
5.	Arteriosclerosis	Partial or complete blockage    of    the blood flow through an artery	Significantly effective	Improvement         in blood  flow  through an artery	Due   to   protein- dissolving   action of serrapeptase	Bracale      et al., 1996
6.	Periodontal disorders	Periodontitis	Better       relief       than antibiotic alone	Serratiopeptidase improves microcirculation  and reduces pain	Effective            in scaling    in    root planning	Maheshwari et al, 2006
7.	Osteoarticular infections	Pain     in     joints, difficult movement	Better       relief       than antibiotic alone	Reduction    in    pain and swelling	Resolution due to anti-inflammatory activity	Okumura   et al., 1977
8.	Obstetrics	Post-partum haematomas,    breast engorgements      and pregnancy       related thrombophlebitis	Significantly effective	Reduction    in    pain and swelling	Resolution due to anti-inflammatory activity	Selan   et   al, 1993

agent   than   any   other   known   alkaline  or   neutral protease. This powerful proteolytic enzyme is obtained from silkworms. It is also  known as serrapeptidase, Serratia peptidase, or serrapeptase. The enzyme is obtained from microorganism Serratia E 15 and HY-6, which live in the gut wall of the silkworm¹. It plays a crucial   role   in   morphological   transformation   of

silkworms. It helps in the proteolysis of cocoons and emergence of the moth. The characteristic feature of this enzyme is its susceptibility for non-living tissues, blood clots, cysts, arterial plaque and inflammation in all forms. The enzyme causes proteolysis of all non- vital tissues - blood clots, cysts, tissue plaques, cellular debris and reduces the inflammatory response. It is one of the most promising proteolytic enzymes in treatment of various types of inflammations. In one study, serrapeptase was compared to trypsin, chymotrypsin, and  pronase  (another  microbial  peptidase)  in  a  rat model of scalding, which is known to induce abnormal activation of fibrinolysis. Serrapeptase was found to be far more effective than any other enzyme in repressing fibrinolysis  in  this  model  as  an  anti-inflammatory

agent⁸.

PROPRIETARY NAMES

Aniflazime, Aniflazym, Bidanzen, Brasan, Cipzen, Dailat,

Danzen, Danzen (FM), Danzyme, Dasen, Dazen, Denzo, Enziflur, Eze, Flanzen (FM), Infladase, Kineto, Korzen, Lergan, Medizyme (FM), Podase, Rodase (FM), Septirose (FM), Seraim, Seramed, Serato-M, Serradase, Serrano, Serrao, Serrapep, Serrason, Serrazyme, Serrin, Sinsia, Sumidin, Unizen, Unizen (FM), Verolin

PRODUCTION

Serratiopeptidase   is   naturally   processed   commercially

through fermentation from the culture of the Serratia marcescens. The controlled fermentation of Serratia sp. secretes this enzyme in the highly selective medium. The recovery process involves various types of filtration, concentration and steps to make enzyme useful for pharmaceutical applications and finally dried to  fine  free flowing powder form^9-10. Ro et al¹¹  studied the effects of carbon sources, nitrogen sources and inducers on the production  of  serratiopeptidase. Citrate  was  found  to  be inhibitory  in   the   production   of   serratiopeptidase.  The enzyme was synthesized in the synthetic medium without inducers showed low level of synthesis. But the synthesis was increased by the addition of proteinaceous substrate and

leucine.  Induction  of  extracellular  proteinase  by  its end-product was discovered, which is not common in the proteinase synthesis in the bacteria. By the glucose fed-batch culture, the possible catabolite repression on the production of serratiopeptidase was demonstrated^12-

¹³.

MECHANISM OF ACTION

It binds to alpha-2-macroglobulin in the blood in ratio of 1:1 which helps to mask its antigenicity but retain its enzymatic activity. Levels of serratiopeptidase are slowly transferred to the exudates at the site of inflammation and gradually the blood level declines. Serrapeptase,  like  aspirin,  is  both  anti-inflammatory and anti-clotting; unlike aspirin, however, serrapeptase can melt through existing fibrous deposits^14-15.

It reduces inflammation in three ways^1,16-17.:

•        It breaks down the insoluble protein by-products of blood coagulation known as fibrin.

•        It thins the fluids formed from inflammation and injury as  well as  facilitating their  drainage that speeds the tissue repair process.

•        It  alleviates  pain  by  inhibiting  the  release  of specific pain-inducing amines called bradykinin.

Serratiopeptidase digests or breaks down protein debris from toxins and inflammation. The healing activity of this enzyme is impressive and includes digesting non-

optimum temperature is 40°C (Stable at 40°C but rapidly losses activity at 60°C in 10 minutes).

CLINICAL USES

This natural anti-inflammatory agent has had wide clinical

use spanning over twenty-five years throughout Europe and Asia as a viable alternative to salicylates, ibuprofen and the more potent NSAIDs^21-24. It is a naturally occurring, physiological agent with no inhibitory effects on prostaglandins and is devoid of gastrointestinal side effects. Clinical studies have shown that serrapeptase induces fibrinolytic, anti-inflammatory and anti-edemic (prevents swelling and fluid retention) activity in a number of tissues (Table1). It is used for the treatment of arthritis, synovitis, and several other inflammatory conditions of muscle and bones². Its anti-inflammatory effects have been found to be superior to other proteolytic enzymes²⁵. This peptidase induces fragmentation of fibrinose 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 by fast resolution of the inflammatory process. Number of successful placebo- controlled  multicentre  studies  has  been  carried  out  to evaluate   the   efficacy   and   tolerability  of   the   Serratia peptidase  in  the  treatment  of  ENT  inflammatory conditions^25-26.

Recent Japanese patents even suggest that oral serrapeptase may help treat or prevent viral diseases such as AIDS and

_15,25

_{living tissue. Since living tissue is not its substrate, it}

^{hepatitis B and C}

^{. But perhaps it’s most spectacular}

_15,27

_{poses    no    harm    to    healthy    tissue    and    cells.}

application is in reversing cardiovascular disease

. In fact,

Serratiopeptidase is involved in the degradation of inflammatory mediators, suppression of edema, activation of fibrinolysis, reduction of immune complexes, and proteolytic modification of cell-surface adhesion molecules that guide inflammatory cells to

serrapeptase  appears  so  effective  in  unblocking  carotid

arteries  that  one  researcher-Dr.  Hans  Nieper,  the  late, eminent internist from Hannover, Germany-called it a "miracle" enzyme²⁷.

their targets¹⁸. Analgesic effect of proteolytic enzymes is due to  their cleavage of  bradykinin, a  messenger molecule   involved   in   pain   signaling.   However,

^{INFLAMMATION:}

The  two  most  common  treatments  for  inflammation  are

_{steroids  such  as  Prednisone  and  NSAID  associated  with}

₂₈

_{according to another theory, peptidases such as trypsin}

^{number of side effects limiting their use}

^{. According to a}

may  be  acting  not  as  anti-inflammatory agents  but rather as accelerants of the inflammatory process, thereby shortening its duration¹⁹. Irrespective of mechanism, many studies of proteolytic enzymes over the years have demonstrated their effectiveness in relieving pain and inflammation independently of NSAIDs¹⁸.

PHARMACOKINETICS

Serratiopeptidase is an acid labile enzyme, so  when

consumed in unprotected form is destroyed by acid in the stomach. However, enterically coated tablets enable the enzyme to pass through the stomach unchanged, and are absorbed in the intestine. Serrapeptase is found in negligible amounts in the urine, suggesting that it is transported directly from the intestine into the bloodstream^7,20. Its optimum pH is 8.5-9.5 and

new  technical  market  research  report,  Therapeutics  for Inflammatory Diseases: Current Challenges and Future Markets (PHM048A) from BCC Research, the market for anti-inflammatory drugs was $21.9 billion in 2005 and is projected to reach $35.5 billion in 2010 at an average annual growth  rate  (AAGR)  of  just  over  10%.  Inflammatory diseases covered in  this  report include ankylosing spondylitis, asthma/COPD, inflammatory bowel diseases, multiple   sclerosis,   psoriasis,   and   rheumatoid   arthritis. Among classes of drugs major share is of NSAIDS which are associated with number of side effects. A statement from the July 1998 issue of The American Journal of Medicine states  that  “...approximately  107,000  patients  are hospitalized annually for NSAID-related gastrointestinal complications and at least 16,500 NSAID-related deaths occur each year among arthritis patients alone.”  Thus there was  the  strong  need  of  a  safe,  alternative  treatment  for people suffering from arthritis and other inflammatory  disorders²⁹. Serratiopeptidase represent a natural alternative to steroids and NSAIDs. Powerful anti- inflammatory   effects   of   this   naturally   occurring enzyme is also supported by histological studies. This immunologically active enzyme is completely bound to the alpha-2 macroglobulin in biological fluids ^{6, 20}. Inflammation is the body’s attempt to restore homeostasis; it is the initial reaction to injury and the first step in the healing process. German researchers conducted one double-blind study 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 fifty 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 completely¹⁷. Moreover, unlike NSAID pain medications, serratiopeptidase does not cause dangerous  internal  bleeding  nor  is  it  addictive  like many pain medications⁶.

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. Thus serrapeptase was concluded to be a safe and effective method for the treatment of breast engorgement^30-32.

Sinusitis/Bronchitis:

In clinical studies serrapeptase has been shown to be

effective in chronic sinusitis and bronchitis and other air way diseases³³. Sinusitis is characterized by hypersecretion  of   thick   mucus  in   patients’   nasal cavities. This thickening causes mucus to be expelled less frequently. 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^34-36. 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 ³⁷.

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 serrapeptase. 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. Serratiopeptidase caused a significant and rapid improvement  of   symptoms  after  3-4  days  in  patients suffering from laryngitis, catarrhal rhinopharyngitis and sinusitis. 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 placebo³⁸. Serratiopeptase and similar protiolytic enzymes³⁹ also reported effecting on dissolving sputum in bronchial asthma ^40-41.

Microbial infections:

Another important feature of serrapeptase is that it improves the delivery of antibiotics such that increased concentrations of the antimicrobial agents reach the site of the infection. Bacteria often endure a process called biofilm formation, which results in resistance to antimicrobial agents. Various means for inhibiting biofilm-embedded bacteria were tried to prevent this bacterial immunity. One  study conducted by Italian researchers suggested 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

^{2, 3, 42-45}.

Another   double-blind   randomized   study   evaluated   the effects of administering the antibiotic sulphobenzylpenicillin in conjunction with serrapeptase⁴⁶. Another study involved the study of effect of Serratiopeptidase on in vivo activity of ciclacillin in treating experimental pneumonia in rats⁴⁷. In both the cases serratiopeptidase treated group experienced significant improvement in response. Serratiopeptidase improves the distribution of antibiotics and thus resulting into significant antimicrobial effects⁴⁸.

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 ^49-50. Thus results demonstrated successful co-delivery of antibiotics with serratiopeptidase for improved efficacy and activity.

Carpal Tunnel Syndrome:

Carpal tunnel syndrome is an inflammatory disorder

(musculoligamentous strain) of the hand and wrist that is characterized by intense, long-lasting pain, inflammation  and  disability.  Among  all  the occupational hazards, it requires more days to recover than any other disorder. NSAIDs and surgery is the general treatment. In a promising small trial, serratiopeptidase improved the inflammation and pain of carpal tunnel syndrome. Sixty five percent of the patients showed clinical improvement. No significant

side effect was observed^51-52.

Cardiovascular Implications:

The effect of serrapeptase on plaque accumulations in the arteries was studied for the first time by Hans A. Nieper, an internist from Hannover, Germany. 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 flow through an artery, resulting in arteriosclerosis, or hardening of the arteries, and an ensuing stroke or heart attack. Still, further studies are required in this area as Nieper's research indicated that the protein-dissolving action of serrapeptase would gradually break down atherosclerotic  plaques⁵³.  Similar  results  were supported by Bracale et al.⁵⁴ in treatment of inflammatory venous disease.

Dentistry:

Serratiopeptidase helps in better control over dental

infections and inflammation. This has been found to be effective in combination with tetracycline delivered as periodontal gel ⁵⁵.

Obstetrics and Gynecology:

The  anti-inflammatory  activity  of  Serratiopeptidase

helps in resolution of post-partum haematomas, breast engorgements and pregnancy related thrombophlebitis. Serratiopeptidase is also effective in treating male genital infections as  it  restores microcirculation and augments antibiotic penetration in these organs which are known to produce poor antibiotic availability.

DOSAGE: Adults:

For    the    treatment    of    Inflammation    and    Pain

recommended  dosage  is  1-3  tablets  of  10mg  three times per day on an empty stomach whereas arterial blockage requires 3 tablets twice daily for first month and then reduced to three per day.

Children and Animals:

It  can  be  safely  used  with  children  and  animals.

_{Recommended  dose  is  1-3  tablets  per  day.  These}

fact a sore throat can be cleared in about 30 minutes by chewing 1-2 tablets treating children with mucus problems such as colds.

Treatment duration:

Although most symptoms disappear within 1-2 weeks, it is recommended for 3-4 months and then evaluated further. For

health maintenance, Serrapeptase can be taken at a low dose,

1-2 per day.

_INTERACTIONS

Serratiopeptidase is  inhibited  by Ni⁺⁺,  Mg⁺⁺,  Cd⁺⁺,  Cu⁺⁺, EDTA inactivates serratiopeptidase. However, activities are

regained by addition of Zn⁺⁺, Mn⁺⁺ and Co^++. The enzyme is not inhibited in presence of di-isopropyl fluorophosphates or p-chloromercuribenzonates. Concomitant use of drug with an anticoagulant may intensify the anticoagulant effect^{2, 20}.

CONTRAINDICATIONS (Miyata, 1980)

•    Patients with blood coagulation disorder

•    Patient with severe hepatic/ renal disorders

•    Hypersensitivity

ADVERSE DRUG REACTIONS

Hypersensitivity: infrequently hypersensitivity reaction such

as rash and redness may occur.

Digestive: diarrhea, anorexia, gastric discomfort, nausea or vomiting.

Hemolysis: rarely bleeding tendency such as epistasis and blood sputum may occur.

A case of pneumonitis, subepidermal bullous dermatosis and acute eosiniphilic pneumonia due to serrapeptase was also reported ^56-58.

ANALYTICAL PROFILE

Serratiopeptidase is not listed in any pharmacopoeia until

this moment. The literature survey reveals a crescent number of publications related to  Serratiopeptidase determination. Tomoda et  al.⁵⁹developed a  highly specific and  sensitive radioimmunossay (RIA) for the determination of Serratiopeptidase. RIA was based upon competition of protease with 125-I labelled protease for anti-protease, followed by antibody to separate bound enzyme from free enzyme. For tablet analysis, there was a chromatographic method reported ⁶⁰. Also, capillary electrophoresis was applied for tablets in aqueous media⁶¹ and for bulk substance in nonaqueous media⁶². HPLC ⁶³  and steric exclusion chromatography⁶⁴ have also been reported for the estimation of serratiopeptidase.  Serratiopeptidase can be estimated in biological fluids by HPLC. The column required is Lichrosorb-CN-l0-and the mobile phase is CH₃OH/ CH₃COONa (4:6) buffer. Flow rate is 1 ml/min. at 800 psi

^{and the system sensitivity was 0.02 with λ}_max ^{at 278nm63.}

Serratiopeptidase   can   also   be   estimated   in   terms   of

proteolytic activity by flurometric method. Fluorescence is developed by using fluorescein isothiocyanate (FITC) – labeled  casein  measured  at  an  excitation  wavelength  of

490nm and emission wavelength of 529 nm. The enzyme can be measured in nanogram and sub nanogram range using

₆₅

tablets can be chewed, as it does not have any taste. In

he assay. Serratiopeptidase can be estimated as protein by  using Bicinchonic acid (BCA) protein assay method. BCA, sodium salt is stable, water soluble compound capable of forming an intense purple color complex with cuprous ion in an alkaline environment. The color produced from this reaction is stable and increases in proportional fashion over a broad range of increasing protein concentration ⁶⁶.

Singh et al reported the spectrophotometric method for determination of Serratiopeptidase and metronidazole in combined dosage forms. It involved the application of  the  derivative spectrophotometric method at  zero crossing wavelengths whereby Serratiopeptidase was measured at 229nm and metronidazole at 346.5nm ⁶⁷. Saudagar et al.⁶⁸  developed and validated a first-order spectrophotometric method for serratiopeptidase determination  in  the  presence  of  formulation excipients. The first-order derivative spectra were obtained over the 200–400 nm range and N=1, ∆λ=1.0 nm. The method uses the derivative spectrophotometric method at zero crossing wavelengths with absorption maxima of Serratiopeptidase at 229.5 nm.

DELIVERY SYSTEMS:

Serratiopeptidase  being  acid  labile  require  special delivery strategies for maximum therapeutic efficacy

and  response.  Generally  these  are  administered  as enteric coated forms to protect the enzymes against the

detrimental effects of acidic gastric environment. But these release the drug as burst in the intestinal region.

Our   group   recently   demonstrated   improved   oral delivery of Serratiopeptidase using ceramic based nanocore system and Eudragit S100 microspheres^69-70. Shah and Paradkar developed cubic liquid crystalline monooleate matrices of serratiopeptidase containing different levels of magnesium trisilicate for oral controlled delivery of enzyme with protection from acidic environment^71-72.

CONCLUSION:

Researchers have  taken a  large  step  toward  finding

relief for inflammatory disease sufferers and the credit goes to the tiny larvae of the silk moth. 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. Inspite of extensive clinical trials, this highly potent enzyme has not been still  listed  in  any  pharmacopoeia.  Looking  into  the broad range of efficacy of this enzyme, there is a need to take steps to include this into official pharmacopoeia so that maximum benefit can be drawn.

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Received on 20.06.2008    Modified on 28.07.2008

Accepted on 30.08.2008   © RJPT All right reserved

Research J. Pharm. and Tech. 1(3): July-Sept. 2008; Page 124-131