GB2216421A - Pharmaceutical compositions acting on the heart and cardiovascular system - Google Patents
Pharmaceutical compositions acting on the heart and cardiovascular system Download PDFInfo
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K35/741—Probiotics
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- A61K36/06—Fungi, e.g. yeasts
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- A61K36/064—Saccharomycetales, e.g. baker's yeast
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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Description
2 6 4 2 PHARMACEUTICAL COMPOSITIONS ACTING PARTICULARLY ON THE HEAIRT AND
CARDIOVASCULAR SYSTEM AND PROCESS FOR PREPARING SAMEE This invention relates to pharmaceutical compositions acting particularly on the thrombo-embolic states of the heart and cardiovascular system.
According to an other aspect of the invention, there is provided a process for the preparation of these compositions.
It is known that C 18-24 W -3 unsaturated fatty acids possess advantageous biological properties. Of these compounds eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are outstanding. Dyerberg et al. /-The Lancet 15, 117 (1978)7 pointed at the importance and multifold biological effects of both acids.
The effects connected with the important role of polyunsaturated fatty acids, particularly of EPA and DHA, in the hyperlipidaemia and thrombotic diseases have bEen summarized by Goodnight et al. /-Arteriosclerosis 2, 87 (1982) Review7- Pharmaceutical compositions containing EPA and DHA as active ingredients have been described e.g. in the German patent specification No. 3,436,630 for lowering the blood cholesterol level, further in the published Japanese patent applications Nos. 58.08037 and 60.49097 against - 2 cerebral sclerosis and for preventing the thrombus formation in patients suffering from heart diseases.
Several papers have been devoted to the platelet-aggregation inhibiting and thus the thrombus-formation inhibiting effect of EPA and DHA /Spencer and Caraega: Prostagl. Leucotrienes and Med. 23, 129 (1986); Knapp et al.: New Engl. Journ. of Med. 314, 937 (1986J.
The antiviral action of EPA and DHA is described in the United States patent specification No. 4,513,008.
The active ingredients of the fish-oil, e.g. EPA and DHA, are precursors of the biosynthesis of the PG-3 series and they inhibit the formation of harmful metabolites such as TXA2 and TXB2 arising from the so-called "arachidonic acid cascade" which is a chain of complicated biochemnical processes starting from arachidonic acid.
In addition to their several favourable effects, the polyunsaturated fatty acids have the disadvantageous pathologic property that they are subjected to a spontaneous oxidative decomposition in the human organism and thus give rise to the formation of active aldehydes such as malondialdehyde which is harmful to the organism. These aldehydes are capable to react mainly with the connective tissues in a physiologically harmful way which may lead to the so-called "ceroidal lipofuscinosis" of the central nervous system.
Investigations on the biological effects of microele,-,,e,-i'LS and trace elements have been started in the last decade. Thus, it became known that selenium is one cf the most important and indispensable substances of life. The beneficial action of selenium is mainly based on its activating effect directed to the glutathione-peroxidase enzyme as selenium is an indispensable constituent of the prosthetic group of the glutathione-peroxidase enzyme. This enzyme is the most important endogenic inhibitor of the harmful peroxidation processes.
Selenium in itself has hypotensive effect, improves the ischaemic, hypoxic and infarction states of the heart and inhibits the ceroidal lipofuscinosis, furthermore, it also exerts a beneficial effect on periodontitis. It has a significant anticancer activity and diminishes the probability of the development of cancer diseases; furthermore, it is considered to be a mutagenesis-inhibiting agent.
Selenium is not accumulated in the organism, thus it should continuously be supplemented. Hitherto, selenium has mainly been introduced to the organism in the form of inorganic compounds, e.g. selenium dioxide and sodium selenite. A number of pathologic alterations or diseases, respectively, such as liver necrosis, myonecrosis, destruction of the erythrocyte membrane, interstitial laesions, ST-elevation in the ECG, Mulberry's heart syndrome, kwashiorkor syndrome (protein malnutrition) and multiplex sclerosis proved to be induced by selenium deficiency.
A comprehensive report on the biological effects of selenium was published by Thressa et al. /-Nutrition Review 35, 7 (1977)7, Shamberger /-J. of Env. Path. and 4 Tox. 4, 305 (1980)7 as well as Masukawa et al. /-Experien-cia 39, 405 (1983)7.
Organic selenium compounds can be obtained by synthetic methods described e.g. by Klaiman and GUnther in their book entitled "Organic Selenium Compounds, Their Chemistry and Biology", John Wiley and Sons, Inc. New York, 1973; besides, organic selenium compounds can be prepared also by using microorganisms. According to the latter method, the microorganisms are cultivated on media enriched with inorganic selenium compounds. Organisms which are suitable to this purpose take up selenium and, introducing it to their metabolism, they bind it to organic substances, most frequently to amino acids or fats. Such possibilities are published by Danch and Chmielowsky /-Pr. Nauk. Univ. Slask Katowich 1, 57 (1985)7 as well as by Gennity et al. Biochem. Biophys. Res. Commun. 118, 176 (1984)7.
A number of microorganisms are known which are capable to collect some elements such as selenium from their environment and to accumulate them in their own organism.
The preparation of yeast enriched with selenium is described in the United States patent specification No. 4,530,846 and in the published Japanese patent applications Nos. 60.224451 and 57.174098.
The enrichment of selenium by other microorganisms such as bacteria, actinomycetes and hyphomycetes, besides the yeast, is described in the published Japanese patent application No. 78.148587.
According to the published Japanese patent application No. 58.129954 selenium-containing yeast in an admixture with vegetable oils is suggested to use for treating senile diseases.
The aim of the present invention is to provide a novel pharmaceutical composition acting on the heart and cardiovascular system which renders possible to combine the advantageous properties of native organic selenium-containing microorganisms with those of DHA and EPA and which s. l wu j. -can eous l y eliminates the disadvantageous properties of polyunsaturated fatty acids.
The invention is based on the recognition that the above aim can be fully achieved and a composition, useful to eliminate ceroidal lipofuscinosis, can be obtained by using a selenium-containing microorganism, being non-toxic from the viewpoint of human use, together with polyunsaturated fatty acids.
Thus, the present invention relates to a pharmaceutical composition acting on the heart and cardiovascular system, which comprises 0,5 to 50% by mass of a selenium-containing microorganism as well as 99.5 to 50% by mass of C18-24 fatty acids containing at least two unsaturated bonds and/or the derivatives thereof, optionally in admixture with carriers and/or additives commonly used in the pharmaceutical industry and optionally with antioxidants.
Furthermore, the invention relates to a process for preparing the above composition, which comprises admixing 0,5 to 50% by mass of a selenium-containing microorganism as well as 99.5 to 50% by mass of C 18-24 fatty acids contain ing at least two unsaturated bonds and/or derivatives there of, optionally with carriers and/or additives, commonly used in the pharmaceutical industry, and optionally with antioxidants, in a manner commonly known in the pharmaceutical industry.
The composition according to the invention suitably comprises eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as selenium-containing yeast.
As raw material of the C 18-24 W-3 unsaturated fatty acids representing one component of the composition, oils obtainable from various marine and fresh-water fishes, mainly from mackerel, cod-fish, herring, sardine, squid as well as from the liver of these fishes, e.g. cod-liver oil and shark-liver oil, can be used.
In addition to EPA and DHA, the fish-oils contain a large amount of saturated fatty acids as well as fatty acids unsaturated to a low extent and other nonhydrolyzable components. The removal of these constituents is very important since the dosis of the therapeutiC21 compositions prepared from the fish-oils would sensitively enhance the introduced calorie quantity as well as the triglyceride level of the blood. Besides, the nonhydrolyzable constituents may contain steroids such as cholesterol, vitamin D (and its provitamin) and/or vitamin A. Vitamins 0 and A are accumulated in the human organism whereby a prolonged treatment, needed to the desired effect, would be impossible by using a composition containing these vitamins. Therefore, the components mentioned above such as the saturated and partly unsaturated fatty acids as well as the nonhydrolyzable constituents, e.g. cholesterol, vitamins A and D, have to be removed from the fish-oil. In this way the. total amount of EPA and DHA in the fish-oil is enriched to more than 50%.
It is suitable to use microorganism strains which are non-toxic to the human organism and are useful for human consumption. Genera widely used in the biotechnology such as Lactobacillus, Leukonostoc, Pediococcus, Acetobacter, Streptococcus, Torula, K1uyveromyces, Candida, Brettanomyces, Brevibacterium, Saccharomyces, Torulopsis, Pichia, Hansenula, Oidium, Rhodotorula, Trichospora, Penicillium, Rhizopus, Mucor, Monascus, Aspergillus, etc. which are useful for human consumption, are most convenient for this purpose.
For inhibiting the oxidation of the composition according to the invention, it is suitable to use ol -tocopherol (vitamin E), glutathione or the traditional antioxidants such as butylhydroxytoluene as active preserv ing agents.
Materials commonly used in the pharmaceutical industry such as lactose, starch or magnesium stearate can be used as vehicle or carrier.
Pharmaceutical investigations proved that the composition is free from side effects damaging the health as no change was observed in the microSomal enzyme system of the rat liver by using a hundred-fold quantity of the usual dose. The amount of lipofuscine accumulated in the organism was significantly decreased as compared to the control after treatment with the composition. Based on investigations carried out by using the composition of the invention on female Wistar rats for 6 weeks, an unambiguous platelet-aggregation inhibiting effect was observed.
The optimum effective daily dose (calculated for an average body-weight of 70 kg) of the composition is from 0.1 to 5 g. The oil component contains 22% of EPA and 43% of DHA as an average. The effective daily dose amounts to 100-300 /ug of selenium.
The main advantages of the composition according to the invention can be summarized as follows:
1. The advantageous properties of EPA and DHA as well as of selenium and the yeast are combined.
2. The harmful effects of the known fish-oil containing compositions, which are induced by saturated lipid components such as sterols as well as vitamins A and D, are diminished or eliminated.
3. The possibility of "ceroidal lipofuscinosis" occurring on the consumption of polyunsaturated fatty acids is removed.
4. The composition contains selenium as native substance enriched in a microorganism such as bacteria, fungi or yeast; the selenium administered together with the specific microorganism is better resorbed and exerts more - 9 preferably its favourable effect.
5. Selenium bound in organic compounds can cheaply be prepared in large amounts specifically enriched in microorganisms, mainly in yeast.
6. The composition develops a favourable therapeutic action in case of atopic disturbances and is useful for the preventive treatment of eczema, asthma, allergic symptoms, allergic rhinitis and/or atopic disturbances such as migraine, CrohnIs disease, ulcerative colitis, otitis media, nephrotic syndrome and diabetes. It is particularly useful for the treatment of disturbances of the cardiovascular system: for apoplectic manifestations, thrombo-embolic states such as stroke, infarction and Keshan syndrome of young patients as well as for the prevention of abnormal conditions.
The invention is illustrated in detail by the following non limiting Examples.
The W-3 polyunsaturated fatty acids used in the composition according to the invention can be prepared according to Example 1 whilst the microorganism enriched with selenium can be prepared as described in Examples 2 to 6. The pharmaceutical compositions according to the invention are illustrated by Examples 7 to 9.
Example 1
8 kg of 40% sodium hydroxide solution are dropped at 50 to 60 0 C to 24 kg of mackerel oil dissolved at 60 0 C in 16 litres of methanol under stirring. Then the mixture is stirred at 60 0 C for additional 45 minutes. After adding kg of 15% hydrochloric ac-id to the solution at about 60 0 C the layers are separated and the organic phase is washed with 10 kg of 15% hydrochloric acid and then with 180 litres of hot tap water until neutral. The phases are i 1 again separated, 100 litres of acetone are added to the oily phase which is then heated to about 45 0 C and 3,B kg of lithium hydroxide dissolved in 30 litres of water are added. After stirring for 30 minutes the mixture is left to stand overnight, then filtered and the acetone filtrate is evaporated. The residue is acidified by adding about 8 kg of 15% hydrochloric acid, extracted 3 times with hexane and the hexane solution is evaporated. Nitrogen atmosphere is used during the whole purifying operation. Thus 6.4 kg of purified fish-oil are obtained.
One kg of the mackerel oil purified as described above is dropped at 60 OC to a solution containing 3 kg of urea in 9 litres of methanol. The mixture is stirred at the same temperature for 2 hours and then cooled. It is left to stand at -10 0 C overnight, then filtered and the filtrate is evaporated. 2.5 litres of 1:1 hydrochloric acid are added to the residue and the mixture is stirred for 15 minutes. After extraction with hexane, the hexane phase is washed with water until neutral, dried over anhydrous sodium sulfate and evaporated to give 0.34 kg of W-3 unsaturated fatty acids with an iodine nuwber of 315 and containing 24% of EPA and 42% of DHA.
Example 2
2 litres of sterilized, liquid malt extract culture medium each are poured into glass bottles of 5 litres volume and the medium is enriched by adding 3% by mass of glucose. After adding 5 /ug/ml of sodium selenite, it is. inoculated with.Saccharomyces cerevisiae and then cultivated under aeration at 32 0 C for 72 hours. An additional amount of 5 /ug/ml of sodium selenite is added to the culture in the 48th hour of cultivation.
After filtration the cells are washed several times with water and dried at 68 to 70 0 C. After micronization, the selenium content is determined by atomic absorption to give a value of 2600 /ug/g.
Example 3 ml. of liquid yeast extract culture medium each are poured in Erlenmeyer. flasks of 500 ml. volume under sterile conditions. After adding 5 /ug/ml of sodium selenite, the medium is inoculated with the fungus Aspergillus sojae, then the cultures are shaken at 28 to 30 0 C. An additional amount of 5 /ug/ml of sodium selenite is added to the culture on the 3rd day of the cultivation. After 5 days the dry material is filtered off, washed and dried as described in Example 2. After micronization, the selenium content of a sample determined by atomic absorption is found to be 3000 /ug/g.
- 12 Example 4
The process described in Example 3 is followed, except that the yeast Torulopsis utilis is used, instead of the fungus. The microbial mass obtained during the cultivation contains 1200 /ug/g of selenium.
Example 5
0 Streptococcus thermophilus is cultivated at 45 C in a culture medium prepared as described in Example 3. After cultivation and working up, the microbial powder contains 4200 /ug/g of selenium.
Example 6
The bacterium Lactobacillus mesenteroides is cultivated as described in Example 3, except that the medium is supplemented by adding 1% of glucose and 2% of calcium carbonate to give a bacterial mass containing 3000 /ug/g of selenium.
Example 7 g of a selenium-containing yeast powder (selenium content: 2600 /ug/g) are added to 150 g of 65% enriched mackerel oil (containing 24% of EPA and 42% of DHA). After homogenization the mixture is preserved by adding 0.15 g of vitamin E. The thus-obtained active agent is filled into soft gelatine capsules and packaged into blister foils.
Example 8
The process described in Example 7 is followed, except that the following starting materials are used: 400 g of 65% enriched cod-liver oil with an EPA content of 22% and DHA content of 43%; 100 g of yeast powder with a selenium - 13 content of 1200 / ug/g; and 0.4 g of vitamin E. The homogenizate is filled into capsules capable of taking up 500 mg of active agent each.
Example 9
The process described in Example 8 is followed., except that 400 g of 30% fish-oil (containing 18% of EPA and 12% of DHA) (produced by Martens and Co., Bergen, Norway) are used as fish-oil component.
Example 10
The process described in Example 8 is followed, except that 400 g of fishoil containing 9.2 % of EPA and 10.4 % of DHA are used as fish-oil component.
Example 11
Tablets with the following composition are prepared by using known pharmaceutical devices and processes:
Cod-liver oil enriched with EPA and DHA and containing 0.1 % of vitamin E (with 2 DHA content of 43% and EPA content of 22%) 200.0 mg Selenium-containing yeast powder (selenium content: 1500 /ug/g) 86.0 mg Lactose 140.0 mg Starch 60.0 mg Polyvinyl pyrrolidone 3.5 mg Magnesium stearate 3.5 mg If desired, the tablets may be coated with sugar or with an other substance in a tabletting machine.
Claims (13)
1. A pharmaceutical composition acting on the heart and cardiovascular system, which c o m p r i s e s 0.5 to 50% by mass of a seleniumcontaining microorganism as well as 99.5 to 50% by mass of C18-24 fatty acids containing at least two unsaturated bonds and/or the derivatives thereof, optionally in admixture with carriers and/or additives commonly used in the pharmaceutical industry and optionally with antioxidants.
2. A composition as claimed in claim 1, which c o m p r i s e s 5-to 35% by mass of the selenium-containing microorganism and 95 to 65% by mass of the unsaturated fatty acids or the d?rivatives thereof.
3. A composition as claimed in claim 1, which c o m p r i s e s 15 to 25% by mass of the selenium-containing microorganism and 85 to 75% by mass of the unsaturated fatty acids.
4. A composition as claimed in claim 1, which c o m p r i s e s fatty acids extracted from the oil of marine fishes as unsaturated fatty acids.
5. A composition as claimed in claim 1, which c o m p r i s e s 5,8,11,14,17-eicosapentaenoic acid and 4,7,10,13,16,19-docosahexaenoic acid as unsaturated fatty acids.
6. A process for the preparation of a pharmaceutical composition acting on the heart and cardiovascular system, which c o m p r i s e s admixing 0.5 to 50% by mass of a selenium -containing microorganism as well as 99.5 to 50% by mass of C 1B- 24 fatty acids containing at least two unsaturated bonds or the derivatives thereof with carriers and/or additives commonly used in the pharmaceutical industry and optionally with antioxidants,in a manner commonly.known in the pharmaceutical industry.
7. A process as claimed in claim 6, i n w h i c h 5 to 35% by mass of the selenium-containing microorganism are admixed with 95 to 65% by mass of the unsaturated fatty acids.
B. A process as claimed in claim 6, i n w h i c h 15 to 25% by mass of the selenium-containing microorganism are admixed with 85 to 75% by mass of the unsaturated fatty acids.
9. A process as claimed in claim 6, which c o m p r i s e s using fatty acids extracted from the oil of marine fishes as unsaturated fatty acids.
10. A process as claimed in claim 6, which c o m p r i s e s using 5,8,11,14,17-eicosapentaenoic acid and 4,7,10,13,16,19-docosahexaenoic acid as unsaturated fatty acids.
11. A mixture of 0.5 to 50% by weight of a selenium containing microorganism and 99.5 to 50% by weight of a C18-24 fatty acid containing at least two unsaturated bonds and/or derivatives of the said acid for therapeutic use.
12. Use of a mixture of 0.5 to 50% by weight of a selenium-containing microorganism and 99.5 to 50% by weight of a C 18-24 fatty acid containing at least two unsaturated bonds - 16 and/or derivatives of the said acid in the preparation of a medicament for use in treating disorders of the heart or of the -reating eczma, asthma, allergic cardiovascular system or for use in t reactions and atopic disturbances.
13. A pharmaceutical composition substance as hereinbefore described in any one of Examples 7 to 11 or containing a fatty acid as described in Example I together with a seleniumcontaining microorganism as described in any one of Examples 2 to 6.
Published 1989 atThe Patent Office, State House, 68.71 High Holbom, London WClR 4TP. Further copies maybe obtained from The PatentOffice. Sales Branch, St Mazy Cray, Orpington, Kent BF.5 3RD. Printed by Multiplex techniques ltd, St Mary Cray, Kent, Con. 1/87
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HU881484A HU210122B (en) | 1988-03-23 | 1988-03-23 | Process for production of composition against thromboembolytic conditions of circulating system and heart |
Publications (2)
Publication Number | Publication Date |
---|---|
GB8906856D0 GB8906856D0 (en) | 1989-05-10 |
GB2216421A true GB2216421A (en) | 1989-10-11 |
Family
ID=10954680
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB8906856A Withdrawn GB2216421A (en) | 1988-03-23 | 1989-03-23 | Pharmaceutical compositions acting on the heart and cardiovascular system |
Country Status (15)
Country | Link |
---|---|
JP (1) | JPH0222228A (en) |
KR (1) | KR890014104A (en) |
BE (1) | BE1003021A3 (en) |
CA (1) | CA1319607C (en) |
CH (1) | CH677732A5 (en) |
DE (1) | DE3909707A1 (en) |
ES (1) | ES2014060A6 (en) |
FI (1) | FI891438A (en) |
FR (1) | FR2628972B1 (en) |
GB (1) | GB2216421A (en) |
HU (1) | HU210122B (en) |
IT (1) | IT1229205B (en) |
LU (1) | LU87488A1 (en) |
NL (1) | NL8900742A (en) |
SE (1) | SE8901041L (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2363331A (en) * | 2000-06-17 | 2001-12-19 | Raymond Clifford Noble | Supplement to enhance fertility |
WO2007071791A1 (en) * | 2005-12-23 | 2007-06-28 | Novamont S.P.A. | Biodegradable artificial baits |
US20080131519A1 (en) * | 2004-12-03 | 2008-06-05 | Sinnex Muszaki Fejileszto Es Tanacsado Kft | Novel Antiviral and Immune Stimulant Pharmaceutical Composition |
EP1501493B1 (en) * | 2002-05-03 | 2009-10-07 | Pronova BioPharma Norge AS | Use of epa and dha in secondary prevention of strokes |
US8535931B2 (en) | 2008-08-29 | 2013-09-17 | Tetrahedron | Non-photosynthetic micro-organisms enriched with organic selenium from seleno-hydroxyacid compounds and applications thereof in the field of nutrition, cosmetics and pharmacueuticals |
US8729124B2 (en) | 2002-03-05 | 2014-05-20 | Pronova Biopharma Norge As | Use of EPA and DHA in secondary prevention |
US9017985B2 (en) | 2008-08-29 | 2015-04-28 | Metabolium | Photosynthetic microorganisms enriched in selenium using selenohydroxy acid compounds, used thereof in nutrition, cosmetics and pharmacy |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3114198B2 (en) * | 1990-11-06 | 2000-12-04 | ソニー株式会社 | Electronics |
KR19990015198A (en) * | 1997-08-02 | 1999-03-05 | 손남율 | Vegetable antibiotics |
BE1012495A3 (en) | 1999-03-02 | 2000-11-07 | Messadek Jallal | Glycine betaine-for its use antithrombotic. |
US7608640B2 (en) | 1999-03-02 | 2009-10-27 | Jallal Messadek | Glycine betaine and its use |
FR2816211B1 (en) * | 2000-11-08 | 2005-04-01 | Brif | NEW DIETETIC AND / OR COSMETIC COMPOSITIONS FOR IMPROVING MUCOUS DROUGHT |
BE1015608A6 (en) | 2003-07-15 | 2005-06-07 | Messadek Jallal | TREATMENT arteritis. |
US20040076695A1 (en) | 2002-07-08 | 2004-04-22 | Advanced Vision Research | EPA and DHA enriched omega-3 supplement for the treatment of dry eye, meibomianitis and xerostomia |
US20060233863A1 (en) | 2003-02-10 | 2006-10-19 | Enzymotec Ltd. | Oils enriched with diacylglycerols and phytosterol esters and unit dosage forms thereof for use in therapy |
FR2863170A1 (en) * | 2003-12-08 | 2005-06-10 | Nicolai Christian Paul Xavier | Composition for regulation and cellular regeneration in the digestive tract, useful e.g. for treating gastroenteritis or improving animal performance, comprises essential oils, shark liver oil, selenium and water |
WO2006016357A1 (en) * | 2004-08-09 | 2006-02-16 | Enzymotec Ltd. | Food products for diabetics |
BRPI0513461A2 (en) | 2004-08-10 | 2011-05-10 | Enzymotec Ltd | Treatment methods requiring phyto ingredients |
WO2006050581A2 (en) | 2004-11-10 | 2006-05-18 | Jallal Messadek | Betaine as agent against arthropod - or mosquito -borne diseases |
WO2006086856A1 (en) | 2005-02-15 | 2006-08-24 | Messadek, Jallal | Combination therapeutic compositions and method of use |
WO2006113978A2 (en) | 2005-04-27 | 2006-11-02 | Jallal Messadek | Insulins combinations |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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GB2203043A (en) * | 1987-03-18 | 1988-10-12 | Caola Kozmetikai | Dietary composition |
GB2203042A (en) * | 1987-03-18 | 1988-10-12 | Caola Kozmetikai | Compositions acting on the heart and cardio-vascular system |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1239587A (en) * | 1983-10-24 | 1988-07-26 | David Rubin | Combined fatty acid composition for lowering blood cholestrol and triglyceride levels |
HU209973B (en) * | 1988-03-09 | 1995-01-30 | Biorex Kutato Fejlesztoe Kft | Process for production of antiviral and immunstimular pharmaceutical composition |
-
1988
- 1988-03-23 HU HU881484A patent/HU210122B/en unknown
-
1989
- 1989-03-20 CH CH1014/89A patent/CH677732A5/de not_active IP Right Cessation
- 1989-03-21 ES ES8901022A patent/ES2014060A6/en not_active Expired - Fee Related
- 1989-03-23 NL NL8900742A patent/NL8900742A/en not_active Application Discontinuation
- 1989-03-23 DE DE3909707A patent/DE3909707A1/en not_active Withdrawn
- 1989-03-23 FR FR8903812A patent/FR2628972B1/en not_active Expired - Fee Related
- 1989-03-23 BE BE8900321A patent/BE1003021A3/en not_active IP Right Cessation
- 1989-03-23 KR KR1019890003678A patent/KR890014104A/en not_active Application Discontinuation
- 1989-03-23 LU LU87488A patent/LU87488A1/en unknown
- 1989-03-23 GB GB8906856A patent/GB2216421A/en not_active Withdrawn
- 1989-03-23 SE SE8901041A patent/SE8901041L/en not_active Application Discontinuation
- 1989-03-23 JP JP1069437A patent/JPH0222228A/en active Pending
- 1989-03-23 IT IT8919876A patent/IT1229205B/en active
- 1989-03-23 FI FI891438A patent/FI891438A/en not_active Application Discontinuation
- 1989-03-23 CA CA000594762A patent/CA1319607C/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2203043A (en) * | 1987-03-18 | 1988-10-12 | Caola Kozmetikai | Dietary composition |
GB2203042A (en) * | 1987-03-18 | 1988-10-12 | Caola Kozmetikai | Compositions acting on the heart and cardio-vascular system |
Non-Patent Citations (1)
Title |
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Derwent abstract no. 83- * |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2363331A (en) * | 2000-06-17 | 2001-12-19 | Raymond Clifford Noble | Supplement to enhance fertility |
GB2363331B (en) * | 2000-06-17 | 2003-02-05 | Raymond Clifford Noble | Supplement to enhance fertility |
US8729124B2 (en) | 2002-03-05 | 2014-05-20 | Pronova Biopharma Norge As | Use of EPA and DHA in secondary prevention |
EP1501493B1 (en) * | 2002-05-03 | 2009-10-07 | Pronova BioPharma Norge AS | Use of epa and dha in secondary prevention of strokes |
CN1665496B (en) * | 2002-05-03 | 2010-05-05 | 派普生物保健品公司 | Use of EPA and DHA in Preparation of medicinie for secondary prevention of neurogenic diseases |
US20080131519A1 (en) * | 2004-12-03 | 2008-06-05 | Sinnex Muszaki Fejileszto Es Tanacsado Kft | Novel Antiviral and Immune Stimulant Pharmaceutical Composition |
US9381213B2 (en) * | 2004-12-03 | 2016-07-05 | Sinnex Muszaki Fejleszto Es Tanacsado Kft | Antiviral and immune stimulant pharmaceutical composition |
WO2007071791A1 (en) * | 2005-12-23 | 2007-06-28 | Novamont S.P.A. | Biodegradable artificial baits |
US8535931B2 (en) | 2008-08-29 | 2013-09-17 | Tetrahedron | Non-photosynthetic micro-organisms enriched with organic selenium from seleno-hydroxyacid compounds and applications thereof in the field of nutrition, cosmetics and pharmacueuticals |
US9017985B2 (en) | 2008-08-29 | 2015-04-28 | Metabolium | Photosynthetic microorganisms enriched in selenium using selenohydroxy acid compounds, used thereof in nutrition, cosmetics and pharmacy |
Also Published As
Publication number | Publication date |
---|---|
ES2014060A6 (en) | 1990-06-16 |
FI891438A0 (en) | 1989-03-23 |
CA1319607C (en) | 1993-06-29 |
GB8906856D0 (en) | 1989-05-10 |
FR2628972B1 (en) | 1994-09-23 |
BE1003021A3 (en) | 1991-10-29 |
HUT60436A (en) | 1992-09-28 |
NL8900742A (en) | 1989-10-16 |
IT8919876A0 (en) | 1989-03-23 |
IT1229205B (en) | 1991-07-25 |
JPH0222228A (en) | 1990-01-25 |
CH677732A5 (en) | 1991-06-28 |
LU87488A1 (en) | 1990-10-02 |
DE3909707A1 (en) | 1989-10-05 |
SE8901041L (en) | 1989-09-24 |
HU210122B (en) | 1995-02-28 |
FR2628972A1 (en) | 1989-09-29 |
KR890014104A (en) | 1989-10-21 |
SE8901041D0 (en) | 1989-03-23 |
FI891438A (en) | 1989-09-24 |
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