CA1314229C - Treatment of lipoprotein disorders associated with cholesterol metabolism - Google Patents
Treatment of lipoprotein disorders associated with cholesterol metabolismInfo
- Publication number
- CA1314229C CA1314229C CA000580218A CA580218A CA1314229C CA 1314229 C CA1314229 C CA 1314229C CA 000580218 A CA000580218 A CA 000580218A CA 580218 A CA580218 A CA 580218A CA 1314229 C CA1314229 C CA 1314229C
- Authority
- CA
- Canada
- Prior art keywords
- blackcurrant
- cholesterol
- treatment
- disorders associated
- lipid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
Abstract
Abstract Blackcurrant seed oil has been found to be particular effective in the treatment of lipoprotein disorders associated with cholesterol metabolism. Its administra-tion enables the cholesterol of the high-density lipoproteins to be significantly increased while reducing the cholesterol of the low-density lipoproteins and thus reduces the cardio-vascular risk.
Description
1314~29 , Treatment of lipoprotein disorders associated with cholesterol metabolism 1 This invention relates to the use of a lipid of the blackcurrant in the treatment of lipoprotein disorders associated with chol~sterol metabolism.
Lipids circulate in the blood in the form of lipopro-teins soluble in aqueous medium which consist of a lipidic nucleus of cholesterol esterified by fatty acids and tri-glycerides surrounded by a layer of proteins, phospholipids and free cholesterol. The arrangement of the various com-ponents characterizes the type of lipoprotein. Numerous epidemiological studies have demonstrated the preponderant role played by the lipoproteins in the development of athero-sclerosis.
In simple terms, it is known that certain lipoproteins, known as low-density lipoproteins (LDL) , represent a cardio-vascular risk factor because there is a positive correlationbetween their presence at high levels in the bloodstream and atherosclerosis. By contrast, high-density lipoproteins (HDL ) represent an anti-cardiovacular risk factor because there is a negative correlation between their levels and the disease. There is thus a ~good cholesterol~ transported by the HDL which drain the cholesterol from the arterial wall and return it to the liver where it is catabolized. By con-trast, the LDL deposit the cholesterol on the arterial wall.
It is known that oils rich in polyunsaturated fatty acids have the effect of reducing the total plasmatic chol-esterol level (TC). However, studies have shown that the fall in the TC is due either to a concomitant reduction in the cholesterol of the LDL (CLDL) and the cholesterol of the HDL (CHDL) or to a reduction in the CLDL with no modifi-cation of the CHDL. According to D,Y. Horrobin et alin Lipids, Vol. 18, No. 8, pages 55~-561, this last case 13~4229 1 would be that of evening primrose oil.
We have surprisingly found that the administration of blackcurrant seed oil produced a a reduction in the CLDL
while significantly increasing the CHDL.
Accordingly, the present invention relates to the use of a lipid of the blackcurrant for preparing a dietetic or pharmaceutical composition for the treatment of lipoprotein disorder~ associated with cholesterol metabolism. - -In the context of the invention, lipoprotein disorders associated with cholesterol metabolism are understood to include - essen~;al hypercholesterolemia (type IIa) characterized by a normal triglyceride level ~TG~, an increase in the TC
corresponding to an increase in the CLDL and to a reduction in, or normal level of, the CHDL, - mi~}ed hyperlipidemia (type IIb) characterized by an in-crease in, or normal level of, the TG , an increase in, or normal level of, the TC corresponding to an increase in the CLDL and to a reduction in the CHDL, dys-beta-lipoproteinemia (type III) characterized by an increase in the TG and in the TC, the latter being dis-tinctly less frequent than the other two, - the anomaly corresponding to a low level of HDL.
In the context of the invention, lipid of the black-currant is understood to be - the oil of blackcurrant seeds (Ribes nigrum) obtained by extraction from blackcurrant residues and refining, for example as described in European patent 92 085 or European patent application 137 862, - a mixture of fatty acids emanating from the hydrolysis or fractionation of blackcurrant seed oil and obtained, for example, in accordance with European patent application no.
178 442 or in accordance with European patent application no 271 747.
- a pharmaceutc;ally acceptable salt of the fatty acids 131~229 1 mentioned above, - an oil obtained by re-esterification of such a mixture of fatty acids with glycerol, - a mixture of the lipids mentioned above.
The blackcurrant lipid may advantageously be protected against oxidation by a liposoluble antioxidant, for example ascorbyl palmitate, tocopherols or a mixture of such anti-oxidants.
The dietetic compositions may be formulated as emul-sions, for example sauces, mayonnaises or margarines.
The pharmaceutical compositions may be made up in various forms according to the method of administration, for example oral, enteral, rectal or parenteral. For exam-ple, it is possible to prepare capsules, gelatin-coated tablets, suppositories or syrups. In the case of enteral or parenteral administration, the compositions are formulated as physically and chemically stabilized, apyrogenic and sterile solutions or emulsions.
The dose administered depends upon the type and serious-ness of the anomaly to be treated. It may comprise from 1to 25 9 blackcurrant lipid and preferably from 2 to 5 g blackcurrant oil daily in a single dose or preferably in two to three separate doses.
The invention is illustrated by the following Example in which the parts and percentages are by weight, unless otherwise indicated.
Example Experimental conditions Patients having an initial TC level of more than 300 mg/dl are treated for 12 weeks with an average daily dose of six gelatin capsules containing either 450 mg blackcurrant seed oil ( BCO`) and 200 ppm (parts per million) ascorbyl pal-mitate or 450 mg grapeseed oil (GS0) and 200 ppm ascorbyl palmitate.
BCO consists of triglycerides of the following fatty 131~229 1 acids (by weight):
linoleic acid~ C18 2~n-~
5 gamma-linolenic acid, C18 3,n 6 with 38% in the beta-position alpha-linolenic acid, C18 3 n-3 13%
with 17% ;n the beta-position 3.5%
stearidonic acid~ C18:4,n-3 with 32% in the beta-position Gamma-linolenic acid is the reaction product of delta-6-desaturase with linoleic acid.
Stearidonic acid is the reaction product of delta-6-desaturase with alpha-linolenic acid.
GS0 contains approximately 70% by weight linoleic acid, 1 to 2% by weight alpha-linolenic acid, but no gamma-linolenic acid or stearidonic acid.
All the patients were given an information sheet of dietetic recommendations.
The group receiving the ~c6 consisted of 5 patients comprising 3 femalesand 2 males with an average age of 61 years (from 36 to 76). The group receiving the GS0 consisted of 7 patients, 4 females and 3 males, with an average age of 55 years (from 48 to 62). In the two groups, the initial TC was similar. In the two groups, the majority of patients were of the IIb type defined above.
Blood samples were taken at intervals of 0, 4, 8 and 12 weeks for analysis of the parameters.
Results Table 1 below shows the mean values of the parameters indicated (X) and the s~andard deviations (SD) for each visit and the probability of the statistical ~est (T test) 13~4229 1 for the two groups. The T test provides an answer to the question: is there any difference between the means of the groups studied and that for each visit? The significant cases (probability < 0.05) are underlined.
The TC (mg/dl) is measured enzymatically from the serum by colorimetry using the enzymes cholesterolesterase, chol-esteroloxidase and the indicator 4-aminophenazine.
The CHDL (mg/dl) is measured in the same way as the TC
on the fraction containing the HDL collected after ultra-cen~rifugation of the serum at 12,000 r.p.m.
The CLDL (mg/dl) is deduced from the value of the CHDL in accordance with Friedewald and Fredrickson.
131422~
o o ~ ,, o 11 ~
_. u) .
xl ~ x i!
======= =a=====~=======
O ,p .p ~ 0 ID ~) ~ .P i~) 11 1~ ~ ~ ~ 0 1 ~ ~ 11 O U~
o ~ o Il Il ~
1~ 11 o ~ ~ `' !' ======= =======~======
o r -- o ,~ 11 o o 11 lll ~ o ~ o ~I o i~, 11 o .P ~ ~ o 11 O
I O .1~ ~n 11 ~
O ,~
$
~ G
======= =======lr======
o , ~ , ~ ii ~ a~ ~ o 11 o o C~ ~, ~ o ,j ~ .~, ,, o , ~ , C~ "
~ o 11 r ~D O ~ O
Il Il r~ 11 o 1~
~i ~ ~ 11 CO
~ ,-- r ,-- o 1l ii O ~-- ~i ~ 0 11 o `i '~
1 Table 2 relates to the probabilities of the paired T tests between the visits V4. Y8, V12 and O
of these statistical tests is to find the differences between the visit VO and the successive visits V4, V8 and V12 for S each group taken separately, i.e. the evolution of the phen-omenon as a function of time. Once again the significant cases are underlined (probability < 0.05).
_5 ~ tD ~ ~
o o o ,, ~ ~ o ~ C) p, ~ ~ 3 C) cr ~ V 11 ~D t'D ;~
_. O --. Il ::5 ~ O
C _ 11 D C
_. ~ --- Il ~ ~ 11 _.
CC ~ ~~ _.
Il ll ll ll ~I ~n ==== ====~==== ===
ll ll . O 11 C
~ 0 11 C
~,11 ~ 11 0 . Il Co --1 r~ o 11 1 c~
,_ ~ 11 C
~ 0 11 0 ll _~
O 0 11 C ~
Il ,_ _ ~_ O 11 ~ ~D
r ._ "
~ o 11 c r~
= = = = = = = ~J~=Q = _ = = =
. . Il .P
O ~ 11 ~ ~ 11 C
O ~ 11 0 ll ll O 0 11 ': C_~
.p 0 11 1 ~1 O IV 11 C r-Oo ~n 11 0 ll . Il ,_ 1~ O ~
Il O
===== ====~=== ===
ll Il .P
~ 0 11 O ~ 11 C
~ a~ 11 o . Il co r-O 0 11 1 C~
~ ,_ 11 C r-00 O~ 11 0 Il C
Il 1 ~D O 11 C
11 o 131~22~
1 Table 3 below studies the CLDL ratio known as the ~standard atherogenicity risk" and the probabilities of the T test. Table 4 below shows the probabilities of the paired T tests. The significant cases are underlined.
Table 3 Groups ,, CLDL/CHDL
''n 0 4 8 12 ==================~========================================
X ',5 6.34 5.63 4.24 3.48 BCO ,, SD ,,5 0.44 0.95 0.34 0.38 ,, .
X ',7 6.86 6.97 6.35 6.93 15 GS0 ll S~ ',7 0.45 0.42 0.49 0.56 Probab;lity " 0.445 0.184 0.010 0.010 Table 4 BCO group Between visits '' V4-Vo V8-VO V12 VO
==================~================================
Probability''n=5 0.259 <0.001 <0.001 ll GS0 group Probab;lityn=7 0.298 0.155 0.740 Conclusions In the BCO group, the mean of the CHDL increased dis-tinctly (+43.5%), the means of the CLDL and the TC decreased ~-23.5% and -15.6%, respectively) and the mean of the stand-ard atherogenicity risk factor decreased from 6.34 to 3.48 ` 1314229 1 during the treatment.
By comparison, the corresponding values of the GSO
group were:
CHDL (-3.2%), CLDL (-1.9%), TC (-3.5~) The mean of the standard atherogenicity risk factor showed hardly any change (from 6.86 to 6.93).
It can thus be seen that the administration of BCO
leads to a reduction in the TC due solely to a decrease in the CLDL without participation of the CHDL which, by con-trast, increases substantially. The standard atherogenicity risk thus decreases considerably.
By contrast, the administration of GSO produces no improvement in the pathological state of the patients.
Lipids circulate in the blood in the form of lipopro-teins soluble in aqueous medium which consist of a lipidic nucleus of cholesterol esterified by fatty acids and tri-glycerides surrounded by a layer of proteins, phospholipids and free cholesterol. The arrangement of the various com-ponents characterizes the type of lipoprotein. Numerous epidemiological studies have demonstrated the preponderant role played by the lipoproteins in the development of athero-sclerosis.
In simple terms, it is known that certain lipoproteins, known as low-density lipoproteins (LDL) , represent a cardio-vascular risk factor because there is a positive correlationbetween their presence at high levels in the bloodstream and atherosclerosis. By contrast, high-density lipoproteins (HDL ) represent an anti-cardiovacular risk factor because there is a negative correlation between their levels and the disease. There is thus a ~good cholesterol~ transported by the HDL which drain the cholesterol from the arterial wall and return it to the liver where it is catabolized. By con-trast, the LDL deposit the cholesterol on the arterial wall.
It is known that oils rich in polyunsaturated fatty acids have the effect of reducing the total plasmatic chol-esterol level (TC). However, studies have shown that the fall in the TC is due either to a concomitant reduction in the cholesterol of the LDL (CLDL) and the cholesterol of the HDL (CHDL) or to a reduction in the CLDL with no modifi-cation of the CHDL. According to D,Y. Horrobin et alin Lipids, Vol. 18, No. 8, pages 55~-561, this last case 13~4229 1 would be that of evening primrose oil.
We have surprisingly found that the administration of blackcurrant seed oil produced a a reduction in the CLDL
while significantly increasing the CHDL.
Accordingly, the present invention relates to the use of a lipid of the blackcurrant for preparing a dietetic or pharmaceutical composition for the treatment of lipoprotein disorder~ associated with cholesterol metabolism. - -In the context of the invention, lipoprotein disorders associated with cholesterol metabolism are understood to include - essen~;al hypercholesterolemia (type IIa) characterized by a normal triglyceride level ~TG~, an increase in the TC
corresponding to an increase in the CLDL and to a reduction in, or normal level of, the CHDL, - mi~}ed hyperlipidemia (type IIb) characterized by an in-crease in, or normal level of, the TG , an increase in, or normal level of, the TC corresponding to an increase in the CLDL and to a reduction in the CHDL, dys-beta-lipoproteinemia (type III) characterized by an increase in the TG and in the TC, the latter being dis-tinctly less frequent than the other two, - the anomaly corresponding to a low level of HDL.
In the context of the invention, lipid of the black-currant is understood to be - the oil of blackcurrant seeds (Ribes nigrum) obtained by extraction from blackcurrant residues and refining, for example as described in European patent 92 085 or European patent application 137 862, - a mixture of fatty acids emanating from the hydrolysis or fractionation of blackcurrant seed oil and obtained, for example, in accordance with European patent application no.
178 442 or in accordance with European patent application no 271 747.
- a pharmaceutc;ally acceptable salt of the fatty acids 131~229 1 mentioned above, - an oil obtained by re-esterification of such a mixture of fatty acids with glycerol, - a mixture of the lipids mentioned above.
The blackcurrant lipid may advantageously be protected against oxidation by a liposoluble antioxidant, for example ascorbyl palmitate, tocopherols or a mixture of such anti-oxidants.
The dietetic compositions may be formulated as emul-sions, for example sauces, mayonnaises or margarines.
The pharmaceutical compositions may be made up in various forms according to the method of administration, for example oral, enteral, rectal or parenteral. For exam-ple, it is possible to prepare capsules, gelatin-coated tablets, suppositories or syrups. In the case of enteral or parenteral administration, the compositions are formulated as physically and chemically stabilized, apyrogenic and sterile solutions or emulsions.
The dose administered depends upon the type and serious-ness of the anomaly to be treated. It may comprise from 1to 25 9 blackcurrant lipid and preferably from 2 to 5 g blackcurrant oil daily in a single dose or preferably in two to three separate doses.
The invention is illustrated by the following Example in which the parts and percentages are by weight, unless otherwise indicated.
Example Experimental conditions Patients having an initial TC level of more than 300 mg/dl are treated for 12 weeks with an average daily dose of six gelatin capsules containing either 450 mg blackcurrant seed oil ( BCO`) and 200 ppm (parts per million) ascorbyl pal-mitate or 450 mg grapeseed oil (GS0) and 200 ppm ascorbyl palmitate.
BCO consists of triglycerides of the following fatty 131~229 1 acids (by weight):
linoleic acid~ C18 2~n-~
5 gamma-linolenic acid, C18 3,n 6 with 38% in the beta-position alpha-linolenic acid, C18 3 n-3 13%
with 17% ;n the beta-position 3.5%
stearidonic acid~ C18:4,n-3 with 32% in the beta-position Gamma-linolenic acid is the reaction product of delta-6-desaturase with linoleic acid.
Stearidonic acid is the reaction product of delta-6-desaturase with alpha-linolenic acid.
GS0 contains approximately 70% by weight linoleic acid, 1 to 2% by weight alpha-linolenic acid, but no gamma-linolenic acid or stearidonic acid.
All the patients were given an information sheet of dietetic recommendations.
The group receiving the ~c6 consisted of 5 patients comprising 3 femalesand 2 males with an average age of 61 years (from 36 to 76). The group receiving the GS0 consisted of 7 patients, 4 females and 3 males, with an average age of 55 years (from 48 to 62). In the two groups, the initial TC was similar. In the two groups, the majority of patients were of the IIb type defined above.
Blood samples were taken at intervals of 0, 4, 8 and 12 weeks for analysis of the parameters.
Results Table 1 below shows the mean values of the parameters indicated (X) and the s~andard deviations (SD) for each visit and the probability of the statistical ~est (T test) 13~4229 1 for the two groups. The T test provides an answer to the question: is there any difference between the means of the groups studied and that for each visit? The significant cases (probability < 0.05) are underlined.
The TC (mg/dl) is measured enzymatically from the serum by colorimetry using the enzymes cholesterolesterase, chol-esteroloxidase and the indicator 4-aminophenazine.
The CHDL (mg/dl) is measured in the same way as the TC
on the fraction containing the HDL collected after ultra-cen~rifugation of the serum at 12,000 r.p.m.
The CLDL (mg/dl) is deduced from the value of the CHDL in accordance with Friedewald and Fredrickson.
131422~
o o ~ ,, o 11 ~
_. u) .
xl ~ x i!
======= =a=====~=======
O ,p .p ~ 0 ID ~) ~ .P i~) 11 1~ ~ ~ ~ 0 1 ~ ~ 11 O U~
o ~ o Il Il ~
1~ 11 o ~ ~ `' !' ======= =======~======
o r -- o ,~ 11 o o 11 lll ~ o ~ o ~I o i~, 11 o .P ~ ~ o 11 O
I O .1~ ~n 11 ~
O ,~
$
~ G
======= =======lr======
o , ~ , ~ ii ~ a~ ~ o 11 o o C~ ~, ~ o ,j ~ .~, ,, o , ~ , C~ "
~ o 11 r ~D O ~ O
Il Il r~ 11 o 1~
~i ~ ~ 11 CO
~ ,-- r ,-- o 1l ii O ~-- ~i ~ 0 11 o `i '~
1 Table 2 relates to the probabilities of the paired T tests between the visits V4. Y8, V12 and O
of these statistical tests is to find the differences between the visit VO and the successive visits V4, V8 and V12 for S each group taken separately, i.e. the evolution of the phen-omenon as a function of time. Once again the significant cases are underlined (probability < 0.05).
_5 ~ tD ~ ~
o o o ,, ~ ~ o ~ C) p, ~ ~ 3 C) cr ~ V 11 ~D t'D ;~
_. O --. Il ::5 ~ O
C _ 11 D C
_. ~ --- Il ~ ~ 11 _.
CC ~ ~~ _.
Il ll ll ll ~I ~n ==== ====~==== ===
ll ll . O 11 C
~ 0 11 C
~,11 ~ 11 0 . Il Co --1 r~ o 11 1 c~
,_ ~ 11 C
~ 0 11 0 ll _~
O 0 11 C ~
Il ,_ _ ~_ O 11 ~ ~D
r ._ "
~ o 11 c r~
= = = = = = = ~J~=Q = _ = = =
. . Il .P
O ~ 11 ~ ~ 11 C
O ~ 11 0 ll ll O 0 11 ': C_~
.p 0 11 1 ~1 O IV 11 C r-Oo ~n 11 0 ll . Il ,_ 1~ O ~
Il O
===== ====~=== ===
ll Il .P
~ 0 11 O ~ 11 C
~ a~ 11 o . Il co r-O 0 11 1 C~
~ ,_ 11 C r-00 O~ 11 0 Il C
Il 1 ~D O 11 C
11 o 131~22~
1 Table 3 below studies the CLDL ratio known as the ~standard atherogenicity risk" and the probabilities of the T test. Table 4 below shows the probabilities of the paired T tests. The significant cases are underlined.
Table 3 Groups ,, CLDL/CHDL
''n 0 4 8 12 ==================~========================================
X ',5 6.34 5.63 4.24 3.48 BCO ,, SD ,,5 0.44 0.95 0.34 0.38 ,, .
X ',7 6.86 6.97 6.35 6.93 15 GS0 ll S~ ',7 0.45 0.42 0.49 0.56 Probab;lity " 0.445 0.184 0.010 0.010 Table 4 BCO group Between visits '' V4-Vo V8-VO V12 VO
==================~================================
Probability''n=5 0.259 <0.001 <0.001 ll GS0 group Probab;lityn=7 0.298 0.155 0.740 Conclusions In the BCO group, the mean of the CHDL increased dis-tinctly (+43.5%), the means of the CLDL and the TC decreased ~-23.5% and -15.6%, respectively) and the mean of the stand-ard atherogenicity risk factor decreased from 6.34 to 3.48 ` 1314229 1 during the treatment.
By comparison, the corresponding values of the GSO
group were:
CHDL (-3.2%), CLDL (-1.9%), TC (-3.5~) The mean of the standard atherogenicity risk factor showed hardly any change (from 6.86 to 6.93).
It can thus be seen that the administration of BCO
leads to a reduction in the TC due solely to a decrease in the CLDL without participation of the CHDL which, by con-trast, increases substantially. The standard atherogenicity risk thus decreases considerably.
By contrast, the administration of GSO produces no improvement in the pathological state of the patients.
Claims (5)
1. The use of a blackcurrant lipid for the treatment of lipoprotein disorders associated with cholesterol metabolism in human, the use being in an amount effective for, over time, increasing CHDL and reducing CLDL levels in the human.
2. The use according to claim 1 wherein a daily dose of from 1 g to 25 g of blackcurrant lipid is used.
3. A method according to claim 1 wherein a daily dose of from 2 g to 5 g of blackcurrant seed oil is used.
4. The use according to claim 1 wherein the blackcurrant lipid is used in the form of a pharmaceutical composition selected from the group of forms for use, consisting of forms for oral, enteral, rectal, and parental use.
5. The use according to claim 1 wherein the blackcurrant lipid is used in the form of a dietetic composition.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH4069/87-0 | 1987-10-16 | ||
| CH4069/87A CH673223A5 (en) | 1987-10-16 | 1987-10-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1314229C true CA1314229C (en) | 1993-03-09 |
Family
ID=4269238
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000580218A Expired - Fee Related CA1314229C (en) | 1987-10-16 | 1988-10-14 | Treatment of lipoprotein disorders associated with cholesterol metabolism |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0311866B1 (en) |
| JP (1) | JPH075471B2 (en) |
| AT (1) | ATE72987T1 (en) |
| AU (1) | AU611204B2 (en) |
| CA (1) | CA1314229C (en) |
| CH (1) | CH673223A5 (en) |
| DE (1) | DE3868827D1 (en) |
| ES (1) | ES2036650T3 (en) |
| GR (1) | GR3003990T3 (en) |
| IE (1) | IE61682B1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6325289U (en) * | 1986-07-31 | 1988-02-19 | ||
| CH676909A5 (en) * | 1988-12-23 | 1991-03-28 | Nestle Sa | |
| JP2917037B2 (en) * | 1990-01-09 | 1999-07-12 | 株式会社アドバンス | ACAT inhibitor |
| US6667064B2 (en) * | 2000-08-30 | 2003-12-23 | Pilot Therapeutics, Inc. | Composition and method for treatment of hypertriglyceridemia |
| JP2006014730A (en) * | 2004-05-31 | 2006-01-19 | Toyo Shinyaku:Kk | Food product |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2834227A1 (en) * | 1978-08-04 | 1980-02-28 | Merck Patent Gmbh | HYPO-BETA -LIPOPROTEINAEMIC DIETETIC, METHOD FOR THE PRODUCTION AND USE THEREOF |
| EP0092076B1 (en) * | 1982-04-16 | 1986-12-17 | Societe Des Produits Nestle S.A. | Lipid composition for oral, enteral or parenteral feeding |
| JPS61118318A (en) * | 1984-11-12 | 1986-06-05 | Pola Chem Ind Inc | Composition having improving action on serum lipid |
-
1987
- 1987-10-16 CH CH4069/87A patent/CH673223A5/fr not_active IP Right Cessation
-
1988
- 1988-10-03 ES ES198888116343T patent/ES2036650T3/en not_active Expired - Lifetime
- 1988-10-03 IE IE298988A patent/IE61682B1/en not_active IP Right Cessation
- 1988-10-03 DE DE8888116343T patent/DE3868827D1/en not_active Expired - Fee Related
- 1988-10-03 AT AT88116343T patent/ATE72987T1/en not_active IP Right Cessation
- 1988-10-03 EP EP88116343A patent/EP0311866B1/en not_active Expired - Lifetime
- 1988-10-05 AU AU23433/88A patent/AU611204B2/en not_active Ceased
- 1988-10-14 CA CA000580218A patent/CA1314229C/en not_active Expired - Fee Related
- 1988-10-14 JP JP63257453A patent/JPH075471B2/en not_active Expired - Lifetime
-
1992
- 1992-03-05 GR GR920400345T patent/GR3003990T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ATE72987T1 (en) | 1992-03-15 |
| EP0311866B1 (en) | 1992-03-04 |
| DE3868827D1 (en) | 1992-04-09 |
| CH673223A5 (en) | 1990-02-28 |
| EP0311866A1 (en) | 1989-04-19 |
| JPH01132530A (en) | 1989-05-25 |
| IE882989L (en) | 1989-04-16 |
| IE61682B1 (en) | 1994-11-16 |
| JPH075471B2 (en) | 1995-01-25 |
| ES2036650T3 (en) | 1993-06-01 |
| AU611204B2 (en) | 1991-06-06 |
| GR3003990T3 (en) | 1993-03-16 |
| AU2343388A (en) | 1989-04-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Davidson et al. | Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial. | |
| AU2003229993B2 (en) | Use of EPA and DHA in secondary prevention | |
| Childs et al. | The contrasting effects of a dietary soya lecithin product and corn oil on lipoprotein lipids in normolipidemic and familial hypercholesterolemic subjects | |
| Hodgson et al. | Can linoleic acid contribute to coronary artery disease? | |
| US5059622A (en) | Method for reducing blood pressure levels in hypertensive persons | |
| AU653353B2 (en) | Food and pharmaceutical compositions containing short chain monounsaturated fatty acids and methods of using | |
| US20110015160A1 (en) | Methods of treating neurological diseases using docosahexaenoic acid and arachidonic acid compositions | |
| Hamazaki et al. | Docosahexaenoic acid-rich fish oil does not affect serum lipid concentrations of normolipidemic young adults | |
| Berr et al. | Dietary N‐3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease | |
| EP1886679A2 (en) | Methods for controlling highly unsaturated fatty acid content in various tissues | |
| EP0524796A1 (en) | Use of essential fatty acids in the preparation of a medicament for the treatment of AIDS | |
| AU2020203658A1 (en) | Administering compositions comprising docosapentaenoic acid | |
| US8729124B2 (en) | Use of EPA and DHA in secondary prevention | |
| US4999380A (en) | Treatment of lipoprotein disorders associated with cholesterol metabolism | |
| CA1314229C (en) | Treatment of lipoprotein disorders associated with cholesterol metabolism | |
| Radack et al. | n-3 fatty acid effects on lipids, lipoproteins, and apolipoproteins at very low doses: results of a randomized controlled trial in hypertriglyceridemic subjects | |
| Bierenbaum et al. | Effects of canola oil on serum lipids in humans. | |
| EP0201159A2 (en) | Pharmaceutical and dietary compositions containing linolenic acids for the treatment of benign prostatic hypertrophy | |
| Svaneborg et al. | The acute effects of a single very high dose of n− 3 fatty acids on plasma lipids and lipoproteins in healthy subjects | |
| JP4688203B2 (en) | Drugs using eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in secondary brain disease events such as stroke | |
| Miller et al. | Triglyceride lowering effect of MaxEPA fish lipid concentrate: a multicentre placebo controlled double blind study | |
| Gotto Jr et al. | The diagnosis and management of hyperlipidemia | |
| CA1334002C (en) | Essential fatty acid compositions and methods for the modulation of prostaglandin levels in mammals | |
| Mustafa | Study of Effects of Cigarette Smoking on Lipid Profile in the Young Subjects Attending AMCH, Vijayapur | |
| JP3177686B2 (en) | Dysmenorrhea prevention or treatment agent and dysmenorrhea prevention functional food |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |