Enzymes, Respiration, and Congested Breathing
last updated 10. 29.05

Seaprose

Mucous is defined as the clear viscid secretion of the mucous membranes, consisting of mucin, epithelial cells and leukocytes. It can build up in the lungs, throat, and sinuses when we are ill. Seaprose is an enzyme that is particularly good on breaking down excess mucous.

Seaprose has at least six separate studies to support the effect it has on individuals with bronchial and sinus mucous as well as inflammatory issues (see studies below). In one study it stated: Eight days after the end of treatment with seaprose, there was still a significant beneficial effect on the viscoelasticity of mucous and a sort of "post-mucolytic effect" can be postulated. The enzyme Seaprose also had anti-inflammatory action, and since in chronic bronchitis there are variable degrees of inflammations, its beneficial long-lasting effect could also be ascribed to this concomitant action."

Amylase has been shown to reduce histamine levels and has antihistamine qualities that may assist those suffering from seasonal allergies or the common symptoms of allergies.

Serratiopeptidase

Here is some good explanations and research on this enzyme:
http://smart-drugs.net/serrapeptase-research.htm http://www.lef.org/magazine/mag2003/sep2003_report_aas_01.htm
http://www.energeticnutrition.com/vitalzym/serrapeptase.html

This enzyme goes by several spellings. More discussion on this enzyme at:
see Serratiopeptidase

MucoStop

MucoStop is a relatively new product from Enzymedica. The active ingredient is a potent mucolytic enzyme known as seaprose which has been studied for its effectiveness
at reducing mucous. MucoStop includes other enzymes blended to assist in overcoming the symptoms often associated with sinus and chest congestion.

Some people have expressed how beneficial MucoStop has been for their asthma, being helpful on a regular basis even they do not have a particular cold. One parent shared how it helped her daughter with asthma be able to run and play on the playground at school with her friends.

Most people use MucoStop as needed for temporary congestion. Feedback from a close relative who gets serious breathing problems with a typical cold said the MucoStop worked within 15 minutes. He was comparing this to over-the-counter antihistamine and congestion products. He said that MucoStop quickly dried up the excess mucous but unlike other over-the-counter medications, it did not over-dry the breathing passages and become painful.

Interestingly, there is a new over-the-counter medication that aims to accomplish the same thing. Mucinex is for temporary relief of excess mucous in the respiratory pathways.

13 Research Studies on Seaprose

1. Anti-inflammatory effects of seaprose-S on various inflammation models.

Fossati A. Drugs Exp Clin Res. 1999;25(6):263-70. PMID: 10713864 [PubMed - indexed for MEDLINE]

The antiinflammatory activity of seaprose-S in different experimental models involving different biochemical mediators of inflammation was investigated. In vivo experiments were performed using male Sprague-Dawley rats and in vitro experiments were performed using articular cartilage explants of pig joints. In acute experimental models of inflammation, 0.5, 1 or 2 mg/kg of seaprose-S was injected intravenously (i.v.) before challenge with inflammatory agents. In adjuvant-induced arthritis, seaprose-S was given as a 2 mg/kg i.v. dose once a day for 4 consecutive days from day 8 after injection of the adjuvant. In cartilage-synovium cocultures, seaprose-S was incubated at a concentration of 0.001 microM and 0.05 microM. Paw volume was measured with a plethysmograph and proteoglycan synthesis was determined in articular cartilage-synovium coculture by incorporation of 35S-sulfate. Seaprose-S inhibited inflammation dose-dependently in carrageenan, concanavalin-A, FeCl2, nystatin-induced paw edema and in carrageenan-induced pleurisy and acetic acid-induced peritonitis. In Freund's adjuvant-induced arthritis, seaprose-S significantly reduced the primary and secondary lesions. In vitro on articular cartilage, seaprose-S increased proteoglycan synthesis in the cartilage alone and reduced the inhibition of proteoglycan synthesis in the cartilage cocultured with minced synovium.
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2. Clinical study of the efficacy of and tolerance to seaprose S in inflammatory venous disease. Controlled study versus serratio-peptidase.

Bracale G, Selvetella L. Minerva Cardioangiol. 1996 Oct;44(10):515-24. PMID: 9091835 [PubMed - indexed for MEDLINE]
Divisione di Chirurgia Vascolare, Universita degli Studi di Napoli, Federico II.

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.

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3. Interactions of alpha-1-antichymotrypsin, alpha-1-proteinase inhibitor, and alpha-2-macroglobulin with the fungal enzyme, seaprose.

Korzus E, Luisetti M, Travis J. Biol Chem Hoppe Seyler. 1994 May;375(5):335-41. PMID: 7521171 [PubMed - indexed for MEDLINE]
Department of Biochemistry, University of Georgia, Athens 30602.

The Semi-alkaline proteinase (Seaprose) from Aspergillus melleus has been tested for its ability to either inactivate or form complexes with three human plasma proteinase inhibitors, alpha-2-macroglobulin, alpha-1-antichymotrypsin and alpha-1-proteinase inhibitor. alpha-2-Macroglobulin was found to inhibit Seaprose, with two mol of enzyme being complexed per mol of inhibitor. However, alpha-1-proteinase inhibitor was rapidly inactivated by the fungal enzyme as a result of cleavage of the inhibitor, primarily at the P1-P'1 reactive site. Curiously, alpha-1-antichymotrypsin was found to form complexes with Seaprose and also be inactivated by this inhibitor. Apparently, the enzyme can recognize two sites within the reactive site loop of the inhibitor, one at the P4-P'5 position, resulting in inactivation, and one presumably at the P1-P'1 reactive site which results in complex formation. The fact that Seaprose can so rapidly inactivate alpha-1-proteinase inhibitor, the primary regulator of neutrophil elastase, indicates that Seaprose would be a rather poor choice for therapy in individuals with bronchial mucus hypersecretion.
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4. The treatment of ENT phlogosis: seaprose S vs. nimesulide.

Antonelli A, Cimino A, Cimino A, Di Girolamo A, Filippi P, Filippin S, Galetti G, Marchiori C, Marcucci L, Mira E , et al. Acta Otorhinolaryngol Ital. 1993;13 Suppl 39:1-16. PMID: 8135108 [PubMed - indexed for MEDLINE]
Clinica ORL, Brescia.

In the present multicentre study, the antiphlogistic activity of seaprose S was assessed according to an experimental design of the controlled type versus nimesulide in patients with phlogistic pathology of ENT relevance and in patients undergoing otoiatric surgical operations. One hundred and sixty patients (87 M, 73 F) were treated with seaprose S in 30 mg tablets (3tab/day) while 160 patients (95 M, 65 F) were treated with nimesulide in 100 mg (2 tab/day). The treatment lasted 7 days. At the beginning of the study, on the 3rd, 7th and 14th day (follow-up) the most significant signs and symptoms present in the pathological forms under consideration were evaluated. Common haematological and haematochemical laboratory parameters were also evaluated and any side effects occurring during the treatment were recorded. Considering the efficacy demonstrated, it was shown how the two drugs used possess an analogous action (NS) and are always able to exert positive control over the symptoms under examination. Administering seaprose S there were 9 cases of unexpected events (5.6%) while with nimesulide 26 patients (16.3%) showed problems of intolerance, with a highly significant statistical difference (p < 0.01) between the two groups. The analysis of the data obtained allows us thus to support the therapeutic use of seaprose S in the treatment of phlogosis of ENT relevance, since it has shown efficacy comparable to that of a NSAID such as nimesulide, but with greater safety.
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5. Double-blind study of nimesulide in divers with inflammatory disorders of the ear, nose and throat.

Banchini G, Scaricabarozzi I, Montecorboli U, Ceccarelli A, Chiesa F, Ditri L, Mazzer G, Moroni R, Viola M, Roggia F, et al. Drugs. 1993;46 Suppl 1:100-2. PMID: 7506144 [PubMed - indexed for MEDLINE]
Medisub (Societa Scientifica dei Medici Specialisti in Medicina Subacquea ed Iperbarica) Istituto Iperbarico, Zingonia, Italy.

200 divers of either sex, aged 18 to 54 years, entered a double-blind study to compare the efficacy and tolerability of nimesulide 200 mg/day with those of seaprose S 60 mg/day in the treatment of nonbacterial inflammatory disorders of the ear, nose, and throat. At the end of the 1-week treatment period, both drugs were judged to be effective, with improvements and, in most cases, complete remission of all symptoms observed. Nimesulide showed greater clinical efficacy, and both drugs were well tolerated.

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6. Effects of seaprose on the rheology of bronchial mucus in patients with chronic bronchitis. A double-blind study vs placebo.

Braga PC, Moretti M, Piacenza A, Montoli CC, Guffanti EE. Int J Clin Pharmacol Res. 1993;13(3):179-85. PMID: 8225701 [PubMed - indexed for MEDLINE]

Centre for Respiratory Pharmacology, School of Medicine, University of Milan, Italy.

There are changes in the rheological characteristics of mucus (viscoelasticity) in several pulmonary pathologies, and especially in chronic bronchitis. Seaprose, a proteolytic enzyme, is one of the pharmacological possibilities for affecting the rheology of bronchial mucus to correct mucostasis and improve its clearance. The action of this drug on the viscoelasticity of bronchial mucus was assessed in a double-blind vs placebo study with 20 randomly balanced chronic bronchitis patients using a new kind of portable rheometer with special features designed for routine bronchial mucus analysis in clinical practice at the patient's bedside. It was found that in the group of patients who were given the placebo, there were no particular changes in the rheological behaviour of mucus, while in those patients who were given seaprose there were significant changes in both viscosity and elasticity at the end of treatment. Eight days after the end of treatment with seaprose, there was still a significant beneficial effect on the viscoelasticity of mucus and a sort of "post-mucolytic effect" can be postulated. Seaprose also had antiinflammatory action, and since in chronic bronchitis there are variable degrees of inflammations, its beneficial long-lasting effect could also be ascribed to this concomitant action.

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7. Effects of seaprose on sputum biochemical components in chronic bronchitic patients: a double-blind study vs placebo.

Moretti M, Bertoli E, Bulgarelli S, Testoni C, Guffanti EE, Marchioni CF, Braga PC. Int J Clin Pharmacol Res. 1993;13(5):275-80. PMID: 8200722 [PubMed - indexed for MEDLINE]
Istituto di Tisiologia e Malattie dell' Apparato Respiratorio, Universita di Modena, Italy.

Seaprose is a semialkaline proteinase endowed with proteolytic effect and antiinflammatory activity tested in different clinical trials. There is clinical evidence that seaprose reduces sputum viscoelastic properties in chronic hypersecretory bronchitis. The present study evaluated (in a double-blind design vs. placebo) the activity of seaprose on bronchial inflammation, mucus glycoprotein secretion and bronchial humoral defence mechanism in chronic bronchitic patients clinically stable (10 per group). Markers of bronchial inflammation (albumin, albumin/total protein ratio) and bronchial infection (DNA), of mucus glycoproteins (fucose and N-acetylneuraminic acid) and of humoral defence mechanism (secretory-IgA) were tested in sputum. We found that ten-day treatment with seaprose (90 mg/day) reduced sputum albumin during the observation period, the difference being statistically significant at the 18th day. The sputum albumin/total protein ratio also decreased by 50% at the end of the study. In the same group, sputum DNA, secretory-IgA, fucose and N-acetylneuraminic acid remained unchanged after treatment. The placebo group did not show any significant changes in the sputum marker substances. This study provides experimental evidence for the antiinflammatory activity of seaprose on bronchial mucosa in chronic bronchitic patients studied in a stable phase of their disease. Furthermore the drug does not seem to affect mucus glycoprotein secretion or secretory-IgA production.

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8. The influence of seaprose on erythromycin penetration into bronchial mucus in bronchopulmonary infections.

Braga PC, Piatti G , Grasselli G, Casali W, Beghi G, Allegra L. Drugs Exp Clin Res. 1992;18(3):105-11. PMID: 1425205 [PubMed - indexed for MEDLINE]

Centre of Respiratory Pharmacology, University of Milan, Italy.

In bronchopulmonary infections antibiotics can be combined with other drugs, called mucoactive drugs, that act to reduce the abnormal viscoelasticity of the mucus enabling a deeper penetration of more antibiotic into the mucus. Seaprose is a protease that interacts with the polymeric fibrillar structure of the bronchial mucus to shorten the long chains of mucoproteins, DNA and other macromolecules, thus reducing the viscosity of the mucus. In order to assess whether the combination of seaprose (60 mg/8 h) plus erythromycin (500 mg/8 h) allows higher antibiotic levels in sputum than erythromycin (500 mg/8 h) plus placebo, the pharmacokinetic behaviour in sputum and in blood of these two treatments was investigated in a double-blind study in two groups of twenty patients each with bronchopulmonary infections. Serum and sputum levels were determined for each patient at the first and seventh day of the two drug regimens. Statistically significant differences for peak, AUC and MRT, were observed for erythromycin between the first and last dose in the group of patients treated with seaprose plus erythromycin; moreover significant differences for these parameters were observed between the two groups. These findings indicate the presence of a pharmacokinetic synergism between seaprose and erythromycin which allows erythromycin to penetrate bronchial secretion more easily and in higher amounts, performing a sterilizing action with therapeutic advantages.
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9. Some properties of the alkaline proteinase from Aspergillus melleus.

Luisetti M, Piccioni PD, Dyne K, Donnini M, Bulgheroni A, Pasturenzi L, Donnetta AM, Peona V. Int J Tissue React. 1991;13(4):187-92. PMID: 1821412 [PubMed - indexed for MEDLINE]
Istituto di Tisiologia e Malattie Respiratoire, IRCCS Policlinico San Matteo, Universita di Pavia, Italy.

Seaprose is a semi-alkaline proteinase produced by Aspergillus melleus. The aim of our study was to further characterize the properties of this enzyme, particularly looking at its interaction with alpha 1-proteinase inhibitor, the major human plasma proteinase inhibitor. We studied the cleavage of three synthetic peptide substrates induced by seaprose and the inhibitory profile of the enzyme by means of a panel of inhibitors, including alpha 1-proteinase inhibitor. The interaction between seaprose and alpha 1-proteinase inhibitor was also studied with SDS-PAGE. Finally, the elastolytic activity of seaprose was checked by means of bovine elastin solubilization. We found that seaprose cleaves preferentially the substrate containing a Phe residue in the P1 position. The inhibitory profile showed that seaprose is a serine-proteinase that cannot be inhibited by alpha 1-proteinase inhibitor. The SDS-PAGE revealed that alpha 1-proteinase inhibitor, after incubation with seaprose, underwent a limited proteolysis. Finally, seaprose 10(-2) M and 10(-3) M was able to solubilize bovine elastin. We conclude that seaprose is a serine-proteinase able to inactivate human alpha 1-proteinase inhibitor with limited proteolysis at (or near) the active site and that it has mild elastinolytic capacity.

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10. In vitro rheological assessment of mucolytic activity induced by seaprose.

Braga PC, Rampoldi C, Ornaghi A, Caminiti G, Beghi G, Allegra L. Pharmacol Res. 1990 Sep-Oct;22(5):611-7. PMID: 2277801 [PubMed - indexed for MEDLINE]
Department of Pharmacology, Chemotherapy and Toxicology, School of Medicine, University of Milan, Italy.

Proteolytic enzymes can act on the polymeric structure of the bronchial mucus, shortening the long chain of mucoproteins, DNA and other macromolecules, and thus reducing the viscosity of the mucus facilitating its expectoration. Seaprose (Flaminase, Puropharma) belongs to this class and is a proteinase from Aspergillus melleus and it is mainly used in traumatology, orthopaedics, gynaecology and pneumology. In the present study the in vitro activity of increasing concentrations (0.25, 0.5, 1%) of seaprose incubated with bronchial mucus samples (1 ml) was investigated by a rheological technique (transient test) that assesses changes in viscosity and elasticity. A dose-effect relationship between increasing concentrations of seaprose and the corresponding reductions in bronchial mucus viscosity was found. There was also a parallel reduction in elasticity after incubation with 0.5%, but an unfortunate distribution of values for 0.25 and 1% concentrations does not allow us to state whether there is a dose-effect relationship for elasticity.
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11. Clinical effectiveness and safety of Seaprose S in the treatment of complications of puerperal surgical wounds.

Dindelli M, Potenza MT, Candotti G, Frigerio L, Pifarotti G. Minerva Ginecol. 1990 Jul-Aug;42(7-8):313-5. PMID: 2293075 [PubMed - indexed for MEDLINE]
I Clinica Ostetrico-Ginecologica, Universita degli Studi L. Mangiagalli, Milano.

The aim of the study was the assessment of the efficacy and safety of Seaprose S in women out patients from the maternity ward with infiltrated surgical wounds subsequent to vaginal birth or caesarean section. The semialkaline proteolithic enzyme Seaprose S, available in 30 mg tablets was administered at a dosage of 3 tablets a day for a period of 8 days. Thirty-two puerpera with a mean age of 31 years +/- 0.9 SE were admitted to the study with an episiotomic wound in 13 cases and a laparotomic wound consequent on caesarean section in the remaining 19 cases. The clinical situation deriving from the surgical wound resolved on average on the 4th day, in particular the swelling and the congestion of the wound had already diminished in the first days of treatment (p less than 0.01). Safety of Seaprose S was good considering that in no cases were side effects attributable to the treatment observed. In conclusion, from the data obtained in this study one may confirm the validity of Seaprose S in the treatment of laparotomic and episiotomic wounds.

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12. Use of a new anti-inflammatory drug in the treatment of varicophlebitis of the lower limbs.

Giorgetti PL , Bortolani EM, Morbidelli A, Vandone PL, Ghilardi G, Mattioli A, Giordanengo F. Minerva Chir. 1990 Jun 30;45(12):883-6. PMID: 2250784 [PubMed - indexed for MEDLINE]
Istituto di Chirurgia Generale e Cardiovascolare dell'Universita di Milano.

The paper reports the results obtained in 20 patients affected by varicophlebitis of the lower limbs following the oral administration of an anti-inflammatory substance. Results were compared with findings in single-blind study performed in a group of 20 patients treated with placebo. The evaluation of residual signs and symptoms and the control of recanalization of venous collectors using Doppler tests revealed a difference between the two groups in favour of the patients treated with the anti-inflammatory agent, although this was not statistically significant. The use of the drug was considered useful as a support to conservative varicophlebitis therapy with the aim of accelerating the resolution of the inflamed condition and thus reducing the functional disability of the limb.

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13. A new method for evaluating mucolytic expectorant activity and its application. II. Application to two proteolytic enzymes, serratiopeptidase and seaprose.

Kase Y, Seo H, Oyama Y, Sakata M, Tomoda K, Takahama K, Hitoshi T, Okano Y, Miyata T. Arzneimittelforschung. 1982;32(4):374-8. PMID: 7049188 [PubMed - indexed for MEDLINE]
Using our new method described in a preceding paper, in vivo effects of two proteolytic enzymes such as serratiopeptidase (SER) and seaprose (SAP) on sputa collected from bronchitis rabbits were examined. SER (20 mg/kg) and SAP (30 mg/kg) significantly reduced the viscosity of sputum (P less than 0.05) at the 1-3-h periods and the 4-6-h periods, respectively, after intraduodenal administration. 50 mg/kg of SER also significantly decreased not only viscosity (P less than 0.001) but also amount of freeze-dried substance (P less than 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 of the increase in volume of sputa. However, the decrease in amount of freeze-dried substance is not always in accord with the reduction viscosity.

Wheezing and Burning: The Link Between Asthma and GERD

abcnews article

Information about Asthma
http://www.nlm.nih.gov/medlineplus/asthma.html
http://asthma.about.com/



 

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