CN1100632A - Gamma-linolenic acid monomer, the prepn. method and application thereof - Google Patents
Gamma-linolenic acid monomer, the prepn. method and application thereof Download PDFInfo
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- CN1100632A CN1100632A CN 94110087 CN94110087A CN1100632A CN 1100632 A CN1100632 A CN 1100632A CN 94110087 CN94110087 CN 94110087 CN 94110087 A CN94110087 A CN 94110087A CN 1100632 A CN1100632 A CN 1100632A
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- gamma
- linolenic acid
- weight
- acid monomer
- oil
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Abstract
The gamma-linolenic acid monomer consists of methyl ester or ethyl ester of mixed fatty acid or a mixture of methyl ester and ethyl ester, the content of gamma-linolenic acid is 12-100% (wt.), the present monomer is prepared from vegetable oil containing gamma-linolenic acid through esterification and inclusion-separation with urea, it can be used to treat cardiovascular and cerebrovascular diseases and obesity.
Description
Medical circle was isolated prostaglandin (Prostaglandins) first and in this class material of later discovery cardiovascular system of human body and other system is had important regulatory role in 1966.Present synthetic prostacyclin (PGI
2), prostaglandin E
1(PGE
1) and prostaglandin E
2(PGE
2) be used for the clinical treatment cardiovascular and cerebrovascular disease, see Vane, J.R.:Prostaglandins and the cardiovascular system.Br.Heart J.49: 45 1983.Because prostaglandin is arachidonic derivant, people are contained the vegetable oil of close fatty acid always in searching, and the gamma-Linolenic acid [CH that found in the vegetable oil in nearly ten years
3-(CH
2-)
3-(CH
2CHCH-)
3-(CH
2-)
4-COOH] balance between the prostaglandin in the human body there is important function, its representative is Radix Oenotherae erythrosepalae oil (O.biennis), sees Pinam.:Oleagineux 1984,39(12), 593-6 page or leaf and United States Patent (USP) 4386072.
The synthetic prostaglandin is used for clinical treatment angina pectoris, hypertension, hyperlipidemia and minimizing thrombosis and is proved to be significant effective, but synthetic PGI
2And PGE
1Expense very high, PGI
2About 2-3 of half-life minute, only stable in alkaline environment.Clinical only can intravenous injection effective; PGE
1Can only vein or intra-arterial injection and long-term infusion can cause the ductus arteriosus strength reduction, and the diarrhoea side effect is arranged.Above shortcoming has greatly limited the application of synthesis of prostaglandins.Oral Evening Primrose Oil is low to the effective percentage of treatment cardiovascular disease, and after taking (half a year-1 year) DeGrain in a short time, main cause is a gamma-linolenic acid content low (8-10% weight) in (1) Radix Oenotherae erythrosepalae oil; (2) Radix Oenotherae erythrosepalae oil is a triglyceride, and is slow in human body metabolism's speed, and most of Radix Oenotherae erythrosepalae oil just is excreted before the epoxidation not carrying out; (3) gamma-Linolenic acid in the Radix Oenotherae erythrosepalae oil distributes with H and is present in the glyceride, and is relatively poor to the selectivity that participates in the influence of blood prostaglandin.
The objective of the invention is to seek out the gamma-Linolenic acid monomer, utilize its high gamma-linolenic acid content, reach in the characteristics such as high selectivity of intravital strong penetration of people and epoxidation and to treat cardiovascular and cerebrovascular disease quickly and effectively, provide simultaneously and make the monomeric economic means of this gamma-Linolenic acid.
Content of the present invention is gamma-Linolenic acid monomer and manufacture method and application
Gamma-Linolenic acid monomer of the present invention is a kind of fatty acid mixed formicester or fatty acid mixed second fat or the two mixture, and wherein the content of gamma-Linolenic acid fat is 12-100%(weight).The purpose that is used for the treatment of cardiovascular and cerebrovascular disease, the monomeric best composition of this gamma-Linolenic acid is:
Gamma-Linolenic acid fat 20-60% weight
Linoleic acid fat 35-70% weight
Olein 0.1-5% weight
Alpha-linolenic acid fat is less than 5% weight
This gamma-Linolenic acid monomer is a light yellow transparent liquid, and proportion 0.88-0.94 grams per milliliter has light fragrance, be dissolved in ethanol, methanol and most of organic solvent, water insoluble, fat and blood vessel there are strong permeability, stable in oxygen-free environment, mean molecule quantity 280-330.
The monomeric manufacture method of this gamma-Linolenic acid is:
(1) one or more is contained gamma-Linolenic acid (C
18H
30O
2) vegetable oil, as Radix Oenotherae erythrosepalae oil, carry out transesterification reaction mixing under 30-80 ℃ of temperature with absolute methanol or dehydrated alcohol under the catalysis of alkali, obtain the formicester or the second lipoprotein mixture of various fatty acids;
(2) above-mentioned fatty acid monoester mixture and methanol or ethanol and carbamide are mixed, each component additional proportion is:
Fatty acid monoester mixture 3-50%(weight)
Methanol or ethanol 0-90%(weight)
Carbamide 15-90%(weight)
Silver nitrate (catalyst) 0-1%(weight)
The heated and stirred said mixture is placed mixture after carbamide dissolving, cooling, treats that crystal separates out, and the solid of separating out is separated with liquid filtering, obtains oil or oily liq;
(3) with above-mentioned oil or liquid washing, the oil that obtains obtains gamma-Linolenic acid monomer of the present invention through vacuum dehydration and desolventizing after making with extra care.
Gamma-Linolenic acid monomer of the present invention is used for the treatment of cardiovascular and cerebrovascular diseases such as people's hypertension, high fat of blood, tremulous pulse medicated porridge sclerosis, coronary heart disease, thrombotic disease, angina pectoris positive effect, also effective to reducing Simple Obesity person's body weight, and can be used as the body-care product.Make capsule through purified gamma-Linolenic acid monomer with gelatin, every capsules contains gamma-Linolenic acid monomer 0.3-0.5 gram, and this soft gelatin capsule can be oral.
With gamma-Linolenic acid monomer of the present invention (gamma-Linolenic acid second fat content 23% weight, linoleic acid second fat content 76% weight) treatment hypertension, the oral above-mentioned gamma-Linolenic acid monomer soft gelatin capsule of 25 routine severe hypertension patients 3 gram/skies, inactive other antihypertensive drugs, mean blood pressure is reduced to 128mmHg by 162mmHg, and generation has no side effect.This effect and input PGI
2Close, but drug cost is PGI
21/30 and clinical easy to use; Compare with oral Evening Primrose Oil, this effect is to adhere to taking about 15 times that Radix Oenotherae erythrosepalae oil acted on after 1 year.
With gamma-Linolenic acid monomer of the present invention (gamma-Linolenic acid second fat content 23% weight, linoleic acid second fat content 76% weight) treatment high fat of blood, the oral above-mentioned gamma-Linolenic acid monomer soft gelatin capsule of 19 routine patients 3 gram/skies, plasma triglyceride on average reduces by 30%, plasma cholesterol slightly descends, and has no side effect.This blood fat reducing effect is faster and obvious than TZn medicine.The Western medicine that majority is used for blood fat reducing has bigger side effect, and the gamma-Linolenic acid monomer utilizes clinical practice in this.Input synthesis of prostaglandins and oral Radix Oenotherae erythrosepalae oil all do not have obvious effect for reducing blood fat.
Oral gamma-Linolenic acid monomer can make PGE in the blood
1Increase, thus atherosclerotic by the gesture minimizing, and vessel softening, but do not have infusion PGE
1The side effect that the blood vessel intensity of bringing reduces.
With gamma-Linolenic acid monomer of the present invention (gamma-Linolenic acid second fat content 25% weight, linoleic acid second fat content 74% weight) treatment coronary heart disease, the oral above-mentioned gamma-Linolenic acid monomer soft gelatin capsule of 11 routine patients 1.8 gram/skies, ejection fraction on average is increased to 0.35 by 0.29, increase by 20%, have no side effect.With import 200ng/kg body weight PGI every day
2Effect is close, is to take two times of diltiazem effect, and expense is PGI
21/60, the side effect that does not have calcium antagonist to bring.
Gamma-Linolenic acid monomer of the present invention can suppress thromboxane A
2, increase PGI
2Body in form PGI
2Strong extension blood vessel and antiplatelet aggregative activity are arranged.Import PGI respectively for two groups of white mouse
2With take gamma-Linolenic acid monomer (gamma-Linolenic acid second fat content 50% weight, linoleic acid second fat content 50% weight), eliminating thrombosis effect gamma-Linolenic acid monomer is PGI
270%.
With gamma-Linolenic acid monomer of the present invention (gamma-Linolenic acid second fat content 25% weight, linoleic acid second fat content 74% weight) treatment angina pectoris, 7 examples produce the oral above-mentioned gamma-Linolenic acid monomer soft gelatin capsule of chemical sproof patient with angina pectoris 3 gram/skies to nitrate drug, 5 routine symptom complete obiterations are wherein arranged, 2 example parts are improved, and have no side effect.
Use gamma-Linolenic acid monomer treatment cardiovascular and cerebrovascular disease of the present invention, clinical effectiveness and synthetic prostacyclin PGI
2And Prostaglandin PGE
1Close, because this gamma-Linolenic acid monomer can orally use, and production cost is low makes its clinical usability be better than PGI
2And PGE
1Because this gamma-Linolenic acid monomer is participated in the balance of various prostaglandins in the body directly, make it more obvious and stable than using Radix Oenotherae erythrosepalae oil and western medicine result on the treatment cardiovascular disease.This gamma-Linolenic acid monomer is half-natural oils and fats, clinical use non-evident effect.
Non-limiting examples of the present invention:
The monomeric manufacturing of example 1 gamma-Linolenic acid
(1) 10 kilograms of refinement of evening primrose oil are heated to 60 ℃, add 3.2 kilograms of dehydrated alcohol (analytical pure) backs of containing 2% sodium hydroxide and stirred 30 minutes under 60 ℃ of temperature, the mixture that will react then washing three times obtains fatty acid mixed second fat;
(2) 5 kilograms in above-mentioned fatty acid mixed second fat is mixed with 20 kilograms of ethanol (industry) and 12.5 kilograms of carbamide (granular), heated and stirred to carbamide all dissolves the back and adds 0.5 gram silver nitrate, under 75 ℃ of temperature, stirred 5 minutes, then material being put into plastic containers leaves standstill, after treating that white crystals is separated out, liquid is separated from crystallization with tripod pendulum type batch centrifugal;
(3) with the above-mentioned liquid heat of separating to 70 ℃, vacuum is steamed and is removed ethanol, obtain a kind of oil-alcohol-urea admixture, obtain oil with after this mixture washing three times, with oily vacuum dehydration to water content less than 0.1%, vacuum take off ethanol to ethanol content less than 5ppm, add the active hargil that is equivalent to weight of oil 0.3% then, 70 ℃ are stirred 20 minutes after-filtration down, obtain 1 kilogram of gamma-linolenic acid content 25% weight, the gamma-Linolenic acid monomer of linoleic acid content 74.8 weight;
(4) above-mentioned monomer is become soft gelatin capsule with gelatin coatings, every seed lac ball contains gamma-Linolenic acid monomer 0.3 gram, pack into soft gelatin capsule light tight or the dark-brown vial in standby.
Example 2 gamma-Linolenic acid monomers are used for the treatment of hypertension and high fat of blood
(1) the oral soft gelatin capsule that obtains by example 1 of patient, 6: 3 balls early, noons 13: 3 ball, late 21: 4 balls, bleeding from anus pressure drop in 3 days is low, blood pressure and blood fat all obviously reduce after 10 days, change behind the oral 5 seed lac balls to 4 month every day blood pressure after 10 days and blood fat is stable keeps normal;
(2) patient is according to routine 2(1) the middle oral soft gelatin capsule that obtains by example 1 of method, take other depressor simultaneously, the reduction effect of blood pressure and blood fat is close with (1).
Example 3 gamma-Linolenic acid monomers are used for the treatment of cerebral embolism
(1) the oral gamma-Linolenic acid monomer of patient soft gelatin capsule (gamma-Linolenic acid second fat content 50% weight, linoleic acid content 50% weight), early 6: 4 balls, noons 13: 4 ball, late 21: 5 balls, (every ball contain gamma-Linolenic acid monomer 0.3 gram), after taking 7 days, resultant effect is better than input and mixes PGI
2And PGE
1, every day the 0.6mg/kg body weight.
(2) soft gelatin capsule the oral as routine 3(1 of patient), every days 2 * 3 ball, infusion PGI simultaneously
2Every day the 0.1mg/kg body weight, effect and infusion PGI
2And PGE
1, every day, the 0.6mg/kg body weight was close, had no side effect.
Example 4 gamma-Linolenic acid monomers are used for the treatment of simple obesity and health care
(1) oral soft gelatin capsule ball every days 2 * 3 that obtains by example 1 of obesity patient, and do not change dietary habit and quantity of motion, weight average descends 5% after one month, cuts out behind the above-mentioned soft gelatin capsule 2 months, and weight average increases by 1.2% and has no side effect.
(2) oral gamma-Linolenic acid monomer of healthy premenopausal volunteers oils and fats (gamma-Linolenic acid second fat content 13.5%, linoleic acid second fat content 84.5%, ethyl oleate 1.8%) restrains every days 3, taking did not continuously have side effect to take place in 6 months, recover score behind the heart movement and be increased to average 110 minutes in average 73 minutes, on average increase by 33% by taking before the monomer.
Claims (3)
1, a kind of gamma-Linolenic acid monomer of being made up of mixed methyl aliphatic ester or mixing-in fat acetoacetic ester or the two mixture is characterized in that gamma-Linolenic acid formicester [CH in this oil
3-(CH
2-)
3-(CH
2CHCH-)
3-(CH
2-)
4-COOCH
3] content or gamma-ethyl linolenate [CH
3-(CH
2-)
3-(CH
2CHCH-)
3-(CH
2-)
4-COOC
2H
5] content, or the two adduction content is 12-100% (weight).
2, a kind of manufacturing gamma-Linolenic acid monomer methods of the present invention:
(1) one or more is contained gamma-Linolenic acid (C
18H
30O
2) vegetable oil, as Radix Oenotherae erythrosepalae oil, carry out transesterification reaction mixing under 30-80 ℃ of temperature with absolute methanol or dehydrated alcohol under the catalysis of alkali, obtain the formicester or the second lipoprotein mixture of various fatty acids;
(2) above-mentioned fatty acid monoester mixture and methanol or ethanol and carbamide are mixed, each component additional proportion is:
Fatty acid monoester mixture 3-50%(weight)
Methanol or ethanol 0-90%(weight)
Carbamide 15-90%(weight)
Silver nitrate (catalyst) 0-1%(weight)
The heated and stirred said mixture is placed mixture after carbamide dissolving, cooling, treats that crystal separates out, and the solid of separating out is separated with liquid filtering, obtains oil or oily liq;
(3) with above-mentioned oil or liquid washing, the oil that obtains obtains gamma-Linolenic acid monomer of the present invention through vacuum dehydration and desolventizing after making with extra care.
3, a kind of gamma-Linolenic acid monomer according to claim 1, it is characterized in that can be used for treating human hypertension, cardiovascular and cerebrovascular disease and simple obesities such as high fat of blood, atherosclerosis, coronary heart disease, thrombotic disease, angina pectoris, and be applied to body-care.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 94110087 CN1100632A (en) | 1994-03-02 | 1994-03-02 | Gamma-linolenic acid monomer, the prepn. method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 94110087 CN1100632A (en) | 1994-03-02 | 1994-03-02 | Gamma-linolenic acid monomer, the prepn. method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1100632A true CN1100632A (en) | 1995-03-29 |
Family
ID=5034077
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 94110087 Pending CN1100632A (en) | 1994-03-02 | 1994-03-02 | Gamma-linolenic acid monomer, the prepn. method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1100632A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1098047C (en) * | 1999-11-03 | 2003-01-08 | 河南省农业科学院农副产品加工研究所 | Newborn pigeon nutrient health care food and preparation process thereof |
-
1994
- 1994-03-02 CN CN 94110087 patent/CN1100632A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1098047C (en) * | 1999-11-03 | 2003-01-08 | 河南省农业科学院农副产品加工研究所 | Newborn pigeon nutrient health care food and preparation process thereof |
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|---|---|---|---|
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| WD01 | Invention patent application deemed withdrawn after publication |