Summary of the invention:
Technical problem to be solved by this invention is: solve common in the market lipid lowerers statins toxic side effect and the plant sterol of crystalline state and the problem that the promise of plant think of gallbladder can not be brought into play its reduction serum cholesterol effect; The invention provides a kind of formula for a product science, carry taking convenience, free from extraneous odour, nontoxic pair of effect, lipid-lowering effect are good, can take separately also and can think the gallbladder promise with compound plant sterol or compound plant that other lipid lowerers are share.
The technical solution used in the present invention is: this have the compound plant sterol that reduces the serum cholesterol effect or compound plant and think the gallbladder promise and adopt heating to melt altogether plant sterol and the promise of plant think of gallbladder be scattered in other medium and be prepared from, these media can be: heat-resisting edible emulsifying agent, perhaps nutrition oils, the mixture of perhaps heat-resisting edible emulsifying agent and nutrition oils.
Above-mentioned heat-resisting edible emulsifying agent can adopt lactic acid stearate, sucrose fatty acid ester etc., and the perhaps bivalent metal ion salt of emulsifying agent is as calcium salt, magnesium salt etc.;
Above-mentioned nutrition oils can adopt Radix Oenotherae erythrosepalae oil or korean pine seed oil, Semen Lini oil, borage seed oil, bathypelagic fish oil, cod-liver oil, vitamin E etc.;
In the technique scheme, prescription and proportioning that compound plant sterol or compound plant are thought the gallbladder promise can be one of the following:
1) plant sterol or plant are thought gallbladder promise and Radix Oenotherae erythrosepalae oil or korean pine seed oil or Semen Lini oil or borage seed oil or bathypelagic fish oil or other nutrition oils such as cod-liver oil or vitamin E, and weight ratio was at 20: 1 to 1: 20;
2) plant sterol or plant are thought gallbladder promise and other heat-resisting edible emulsifying agents such as lactic acid stearate or sucrose fatty acid ester, and weight ratio was at 20: 1 to 1: 5;
3) plant sterol or plant are thought gallbladder promise (10%-80% gross weight) and heat-resisting edible emulsifying agent (2%-80% gross weight) and Radix Oenotherae erythrosepalae oil or korean pine seed oil or Semen Lini oil or borage seed oil or bathypelagic fish oil or other nutrition oils such as cod-liver oil or vitamin E (2%-80% gross weight) such as lactic acid stearate or sucrose fatty acid ester.
Can not give full play to the effect that it reduces serum cholesterol because the plant sterol of crystalline state and plant are thought the gallbladder promise, the present invention adopts to heat to melt altogether plant sterol or the promise of plant think of gallbladder is scattered in other medium.These media have has emulsification, and can promote plant sterol or plant to think the gallbladder promise and mix the emulsifying corpusculum, as calcium stelate, heat-resisting edible emulsifying agent such as sucrose fatty acid ester; The effect that itself has blood fat reducing that has, as Radix Oenotherae erythrosepalae oil, korean pine seed oil, Semen Lini oil, borage seed oil, bathypelagic fish oil, cod-liver oil, vitamin E etc.These media are to all nontoxic pair effect of human body.The plant sterol or the plant that are scattered in these media are thought the effect that the gallbladder promise can be brought into play the inhibition cholesterol absorption better.Medium with effect of blood fat reducing then may be strengthened the effect that plant sterol or plant are thought gallbladder promise reduction serum cholesterol.The plant sterol or the promise of plant think of gallbladder that are scattered in the medium can be made into tablet or other dosage form of carrying taking convenience, for hypercholesterolemiapatients patients provides more blood fat reducing approach.
Plant sterol or the promise of plant think of gallbladder also can be scattered in and have the emulsification medium and have in the mixture of effect for reducing fat medium, bring into play the effect of various compositions, reach better lipid-lowering effect.
The invention provides plant sterol or plant and think the compound recipe prescription of gallbladder promise, just can manufacture compound plant sterol or compound plant with simple program and think gallbladder promise tablet and other dosage forms, carry taking convenience.Experimental results show that the compound plant sterol that is provided has lipid-lowering effect preferably.
Formula for a product science provided by the invention is carried taking convenience, and free from extraneous odour has no side effect, and lipid-lowering effect is sure, can take separately or share to reduce other fat-reducing medicament dosage with other lipid lowerers under physician guidance.
The specific embodiment:
1. plant sterol or plant are thought gallbladder promise/Radix Oenotherae erythrosepalae oil or korean pine seed oil, Semen Lini oil, borage seed oil, other nutrition oils prescription of bathypelagic fish wet goods
Plant sterol (or plant think gallbladder promise) and Radix Oenotherae erythrosepalae oil (or korean pine seed oil, Semen Lini oil, borage seed oil, bathypelagic fish oil, cod-liver oil, other nutrition oils such as vitamin E) are placed at mixing in the heatproof container.Weight ratio was at 20: 1 to 1: 20.Be heated to about 140 degree Celsius.This moment, plant sterol became liquid.With itself and Radix Oenotherae erythrosepalae oil mixing, be cooled to room temperature while stirring and become solid, shaped or pasty state.With pulverizer the solid, shaped mixture is broken into powder, this powder or pasty mixture get final product and excipient, and flavoring agent etc. are made tablet, capsule, mouthful quick-dissolving agent, chewing agent etc.
Formula examples 1 (tablet):
Plant sterol and Radix Oenotherae erythrosepalae oil heating back mixture of powders, 1 kilogram of weight ratio 5: 1
1.5 kilograms of excipient
Flavoring agent is an amount of
Toner is an amount of
Dosage: 400 milligrams of plant sterol/sheets, a 1-2 sheet, 2-10 sheet/sky
Instructions about how to take medicine: chew under the posterior phraynx tablet is fine.Obey before the meal.Also can take at ordinary times.
Formula examples 2 (blob of viscose agent):
Plant sterol and Radix Oenotherae erythrosepalae oil heating back pasty mixture, 1 kilogram of weight ratio 1: 1
5.25 kilograms of colloid excipient
Flavoring agent is an amount of
Toner is an amount of
Be heated to nearly 100 degree, vigorous stirring becomes suspension.5 grammes per square metre fritters are cut in cooling after the cooling while stirring.
Dosage: 400 milligrams of plant sterol/pieces, a 1-2 piece, 2-10 piece/sky
Instructions about how to take medicine: fine the chewing under the posterior phraynx of blob of viscose got final product.Obey before the meal.Also can take at ordinary times.
Formula examples 3 (oral liquid):
Plant sterol and Radix Oenotherae erythrosepalae oil heating back pasty mixture, 1 kilogram of weight ratio 1: 1
11.5 liters of 1% sucrose fatty acid ester
Flavoring agent is an amount of
Spice is an amount of
Plant sterol and Radix Oenotherae erythrosepalae oil heating back pasty mixture is heated to nearly 100 degree makes into aqueously, add in about 95 degree, 1% sucrose fatty acid ester, vigorous stirring (or ultrasonic wave concussion) is to emulsion suspension liquid uniformly.Cooling while stirring is sub-packed in the sterile vials sealing after the cooling.
Dosage: 400 milligrams of plant sterol/10 milliliter, one time 10 milliliters, 20-100 milliliter/sky
Instructions about how to take medicine: obey before the meal.Also can take at ordinary times.
2. plant sterol or plant are thought other edible emulsifiers formulas such as gallbladder promise/lactic acid stearate or sucrose fatty acid ester.As possible, the bivalent metal ion salt of available emulsifying agent (calcium salt, magnesium salt etc.) has the report bivalent metal ion to have and strengthens the effect that plant sterol reduces serum cholesterol.
With plant sterol (or plant think gallbladder promise) and calcium stelate other edible emulsifying agents such as (or) sucrose fatty acid ester mixing in heatproof container.Weight ratio was at 20: 1 to 1: 5.Be heated to about 140 degree Celsius.This moment, plant sterol all became liquid with calcium stelate.With the two mixing, be cooled to room temperature and become solid.The reuse pulverizer is broken into powder with it.This powder gets final product and excipient, and flavoring agent etc. are made tablet, mouthful quick-dissolving agent, chewable tablet etc.
Formula examples 1:
1 kilogram of plant sterol and calcium stelate powder mixture (weight ratio 4: 1)
1.4 kilograms of excipient
Flavoring agent is an amount of
Toner is an amount of
Dosage: 400 milligrams of plant sterol/sheets, a 1-2 sheet, 2-10 sheet/sky
Instructions about how to take medicine: chew under the posterior phraynx tablet is fine.Obey before the meal.Also can take at ordinary times.
Formula examples 2:
1 kilogram of plant sterol and calcium stelate powder mixture (weight ratio 5: 4)
5.94 kilograms of colloid excipient
Flavoring agent is an amount of
Toner is an amount of
Be heated to nearly 100 degree and make into aqueously, vigorous stirring becomes suspension.5 grammes per square metre fritters are cut in cooling after the cooling while stirring.
Dosage: 400 milligrams of plant sterol/pieces, a 1-2 piece, 2-10 piece/sky
Instructions about how to take medicine: fine the chewing under the posterior phraynx of blob of viscose got final product.Obey before the meal.Also can take at ordinary times.
3. plant sterol or plant are thought other edible emulsifying agent/Radix Oenotherae erythrosepalae oil or korean pine seed oils such as gallbladder promise/lactic acid stearate or sucrose fatty acid ester, Semen Lini oil, and borage seed oil, other nutrition oils prescription of bathypelagic fish wet goods:
With plant sterol (10%-80% gross weight) and calcium stelate (or heat-resisting edible emulsifying agent such as sucrose fatty acid ester, the 2%-80% gross weight), Radix Oenotherae erythrosepalae oil (or korean pine seed oil, Semen Lini oil, borage seed oil, other nutrition oils of bathypelagic fish wet goods, 2%-80% gross weight) is placed at mixing in the heatproof container.Be heated to about 140 degree Celsius.This moment, plant sterol and calcium stelate and Radix Oenotherae erythrosepalae oil were liquid state.Plant sterol and calcium stelate and Radix Oenotherae erythrosepalae oil mixing with liquid state are cooled to room temperature and become solid, shaped or pasty state.With pulverizer the solid, shaped mixture is broken into powder, this powder or pasty mixture get final product and excipient, and flavoring agent etc. are made tablet, chewing agent etc.
Formula examples 1:
Plant sterol/calcium stelate/Radix Oenotherae erythrosepalae oil mixture of powders, 1 kilogram of weight ratio 4: 1: 1
1 kilogram of excipient
Flavoring agent is an amount of
Toner is an amount of
Dosage: 400 milligrams of plant sterol/sheets, the 1-2 sheet/time, 2-10 sheet/sky
Instructions about how to take medicine: chew under the posterior phraynx tablet is fine, before the meal clothes.Also can take at ordinary times.
Formula examples 2:
Plant sterol/calcium stelate/Radix Oenotherae erythrosepalae oil heating back pasty mixture, 1 kilogram of weight ratio 5: 1: 4
5.25 kilograms of colloid excipient
Flavoring agent is an amount of
Toner is an amount of
Be heated to nearly 100 degree, vigorous stirring becomes suspension.5 grammes per square metre fritters are cut in cooling after the cooling while stirring
Dosage: 400 milligrams of plant sterol/pieces, the 1-2 piece/time, 2-10 piece/sky
Instructions about how to take medicine: chew under the posterior phraynx tablet is fine.Obey before the meal.Also can take at ordinary times.
Formula examples 3 (oral liquid):
Plant sterol/calcium stelate/Radix Oenotherae erythrosepalae oil pasty mixture, 1 kilogram of weight ratio 5: 1: 5
10.36 liters of 1% sucrose fatty acid ester
Flavoring agent is an amount of
Spice is an amount of
Plant sterol/calcium stelate/Radix Oenotherae erythrosepalae oil pasty mixture be heated to nearly 100 the degree make into aqueous, add about 95 the degree 1%
In the sucrose fatty acid ester, vigorous stirring (or ultrasonic wave concussion) is to uniform emulsion suspension liquid.Cooling while stirring is after the cooling
Be sub-packed in the sterile vials sealing.
Dosage: 400 milligrams of plant sterol/10 milliliter, one time 10 milliliters, 20-100 milliliter/sky
Instructions about how to take medicine: obey before the meal.Also can take at ordinary times.
Above technical scheme and the specific embodiment for example in the available equivalent plant of plant sterol (phytosterol, plant sterol) think gallbladder promise (plant stanol, phytostanol) replacement.
. the experimentation of the effect for reducing fat of compound plant sterol
Adopt high lipid food (adding 1% cholesterol, 10% Adeps Sus domestica in the rat normal feedstuff) to make the rat high blood lipid model.In high lipid food, add following three kinds of compound plant sterol prescriptions respectively:
Prescription 1: plant sterol and bathypelagic fish oil heating back pasty mixture, weight ratio 1: 1
Prescription 2: plant sterol and Radix Oenotherae erythrosepalae oil heating back pasty mixture, weight ratio 1: 1
Prescription 3: plant sterol and calcium stelate sodium heating back powder mixture, weight ratio 1: 1
With the grouping of Wistar rat, according to the form below gives DIFFERENT FEED and raised for 4 weeks:
Group is handled
Normal feedstuff group normal rat feedstuff
The high fat rat feed of high lipid food group
High lipid food+prescription 1 high fat rat feed adds prescription 1 (100: 1)
High lipid food+prescription 2 high fat rat feeds add prescription 2 (100: 1)
High lipid food+prescription 3 high fat rat feeds add prescription 3 (100: 1)
After raising, get blood and survey serum total cholesterol (TC), end density lipoprotein cholesterol (LDLC), HDL-C (HDLC) and serum triglycerides (TG).The result is as follows:
TC LDLC HDLC TG
Normal feedstuff group 1.825+0.116 0.199+0.023 0.650+0.044 0.849+0.092
High lipid food group 2.653+0.182 0.358+0.043 0.966+0.056 0.849+0.110
High lipid food+prescription 1 1.715+0.128 * 0.233+0.021 * 0.687+0.063 0.721+0.159
High lipid food+prescription 2 1.623+0.110 * 0.204+0.025 * 0.636+0.054 0.798+0.080
High lipid food+prescription 3 1.532+0.093 * 0.178+0.027 * 0.592+0.037 0.922+0.128
* compare P<0.05 with the high lipid food group
Above result shows that three kinds of prescriptions all significantly reduce hyperlipemia rat serum total cholesterol and end density lipoprotein cholesterol.
Compound plant sterol partial elements physicochemical property and biological nature
The physicochemical property of plant sterol (phytosterol), structure and biological nature:
Plant sterol is the steroidal compounds that a class is extracted from Semen sojae atricolor or other plant.The plant sterol that extracts from Semen sojae atricolor mainly contains:
Sitosterol (Beta-SITOSTEROL): 40-58%
Stigmasterol (STIGMASTEROL): 14-22%
Campesterol (CAMPESTEROL): 20-30%
This type of steroidal compounds is all tasteless white crystal.Stable.Water insoluble, be dissolved in organic solvents such as chloroform.
Sitosterol (Beta-SITOSTEROL)
Molecular formula: C
29H
50O
Molecular weight: 414.7134
Molten point: 139-142 ℃
Structural formula:
Stigmasterol (STIGMASTEROL)
Molecular formula: C
29H
48O molecular formula: C
29H
48O molecular weight: 412.6976 molten points: 160-164 ℃ of structural formula:
Campesterol (CAMPESTEROL) molecular formula: C
28H
480 molecular weight: 400.6866 molten points:
Plant sterol and plant are thought the gallbladder promise all can suppress the absorption of enterocyte to cholesterol in vivo and in vitro.Plant sterol and plant are thought the mechanism of gallbladder promise inhibition cholesterol absorption does not also have final conclusion.But because the structure of plant sterol and plant think of gallbladder promise and cholesterol is quite similar, generally believe the two the same emulsifying corpusculum (micelle) that mixes, suppress the absorption of cholesterol, reduce serum cholesterol with cholesterol.Plant sterol and plant are thought gallbladder promise itself and seldom are absorbed, and have no side effect.
Plant is thought the gallbladder promise can be by the plant sterol dehydrogenation.Itself and plant sterol structure do not exist together and only are to be singly-bound between the 5th and the 6th carbon atom.The biological characteristics of the two inhibition cholesterol absorption is similar.
1.Matvienko?OA,Lewis?DS,Swanson?M,Arndt?B,Rainwater?DL,Stewart?J,Alekel?DL.A?single?daily?dose?of?soybean?phytosterols?in?ground?beef?decreases?serum?totalcholesterol?and?LDL?cholesterol?in?young,mildly?hypercholesterolemic?men.Am?JClin?Nutr?200;76(1):57
2.Mussner?MJ,Parhofer?KG,Von?Bergmann?K,Schwandt?P,Broedl?U,Otto?C.Effects2002,51(2):189
3.Vaskonen?T,Mervaala?E,Krogerus?L,Karppanen?H.Supplementation?of?plant?sterolsand?minerals?benefits?obese?Zucker?rats?fed?an?atherogenic?diet.J?Nutr?2002,132(2):231
4.Jones?PJ,Howell?T,MacDougall?DE,Feng?JY,Parsons?W.Short-term?administrationof?tall?oil?phytosterols?improves?plasma?lipid?profiles?in?sub?jects?with?differentcholesterol?levels.Metabolism?1998,47(6):751
5.Pelletier?X,Belbraouet?S,Mirabel?D,Mordret?F,Perrin?JL,Pages?X,Debry?G.Adiet?moderately?enriched?in?phytosterols?lowers?plasma?cholesterol?concentrationsin?normocholesterolemic?humans.Ann?Nutr?Metab?1995;39(5):291
6.Moreau?R,Whitaker?B,Hicks?K.Phytosterols,phytostanols,and?their?conjugatesin?foods:structural?diversity,quantitative?analysis,and?health-promoting?uses.Prog?Lipid?Res?2002,41(6):457
7.Amundsen?AL,Ose?L,Nenseter?MS,Ntanios?FY.Plant?sterol?ester-enriched?spreadlowers?plasma?total?and?LDL?cholesterol?in?children?with?familialhypercholesterolemia.Am?J?Clin?Nutr?2002;76(2):338
8.Hayes?KC,Pronczuk?A,Wijendran?V,Beer?M.Free?phytosterols?effectively?reduceplasma?and?liver?cholesterol?in?gerbils?fed?cholesterol.J?Nutr?2002Jul;132(7):1983
9.Vaskonen?T,Mervaala?E,Sumuvuori?V,Seppanen-Laakso?T,Karppanen?H.Effects?ofcalcium?and?plant?sterols?on?serum?lipids?in?obese?Zucker?rats?on?a?low-fat?diet.Br?J?Nutr?2002;87(3):239
10.Ostlund?RE?Jr,Racette?SB,Okeke?A,Stenson?WF.Phytosterols?that?are?naturallypresent?in?commercial?corn?oil?significantly?reduce?cholesterol?absorption?inhumans.Am?J?Clin?Nutr?2002?Jun;75(6):1000
11.Vanstone?CA,Raeini-Sarjaz?M,Jones?PJ.Injected?phytosterols/stanols?suppressplasma?cholesterol?levels?in?hamsters.J?Nutr?Biochem?2001;12(10):565
12.Nissinen?M,Gylling?H,Vuoristo?M,Miettinen?TA.Micellar?distribution?ofcholesterol?and?phytosterols?after?duodenal?plant?stanol?ester?infusion.Am?JPhysiol?Gastrointest?Liver?Physiol?2002?Jun;282(6):G1009
13.Jones?PJ,Ntanios?FY,Raeini-Sarjaz?M,Vanstone.Cholesterol-lowering?efficacyof?a?sitostanol-containing?phytosterol?mixture?with?a?prudent?diet?inhyperlipidemic?men.Am?J?Clin?Nutr?1999,69(6):1144