CN101062025A - Compound anget for reducing weight, fat, sugar, pressure and for preventing and treating osteoporosis - Google Patents

Compound anget for reducing weight, fat, sugar, pressure and for preventing and treating osteoporosis Download PDF

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CN101062025A
CN101062025A CN 200710028374 CN200710028374A CN101062025A CN 101062025 A CN101062025 A CN 101062025A CN 200710028374 CN200710028374 CN 200710028374 CN 200710028374 A CN200710028374 A CN 200710028374A CN 101062025 A CN101062025 A CN 101062025A
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carnitine
calcium
conjugated linoleic
linoleic acid
compound preparation
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CN100539999C (en
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杨得坡
梁淑明
李珍
冀军峰
曾晓晖
鲁冰山
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YOULIKA NATURAL DRUG CO Ltd ZHONGSHAN CITY
National Sun Yat Sen University
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YOULIKA NATURAL DRUG CO Ltd ZHONGSHAN CITY
National Sun Yat Sen University
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Abstract

The invention discloses a compound preparation for fat-reducing, antihyperglycemic, antihypelipidemic and osteoporosis in medical domain, which is characterized by the following: setting mass ratio of adjoint linolic acid calcium and left-handed carnitine or derivation of adjoint linolic acid calcium and left-handed carnitine at 4 : 1-8; producing to tablet, capsule, powder medicine and granula with compound preparation. This invention possesses simple preparation and convenient usage.

Description

Be used for fat-reducing, blood fat reducing, blood sugar lowering, blood pressure lowering, the osteoporotic compound preparation of control
Technical field
The present invention relates to field of medicaments, be specifically related to be used for fat-reducing, blood fat reducing, blood sugar lowering, blood pressure lowering, prevent and treat osteoporosis, contain the compound preparation of calcium conjugated linoleic acid and L-carnitine or calcium conjugated linoleic acid and L-carnitine derivant.
Background technology
Along with the high speed development of society, the raising of people's living standard, many modern diseasies are just threatening human beings'health as obesity, hypertension, hyperlipidemia, diabetes, osteoporosis etc., the control of modern disease have been become the problem of human concern.Obesity usually collects with " three-hypers " (hypertension, hyperlipidemia and hyperglycemia) to be sent out in same one, has become worldwide epidemic diseases, and the cardiovascular and cerebrovascular disease that brings out thus, M ﹠ M have occupied the various diseases first place.Lipid metabolism and glycometabolic disorder often appear in the overweight people.The diabetes patient is also with hypertension, hyperlipidemia, and patient is not as controlling blood fat and blood pressure, behind the 5-10 that falls ill with regard to easy diabetes.And lipid metabolism, carbohydrate metabolism disturbance impel the hypertension prevalence to raise.Therefore, for fear of the generation of cardiovascular and cerebrovascular disease, except controlling well the body weight, the prevention of hypertension, hyperlipidemia and hyperglycemia or treatment also can not be ignored.
Conjugated linoleic acid (being called for short CLA) and L-carnitine (being called for short the L-carnitine) all are nutrient substance and the functional components that body weight for humans is wanted.
Carnitine has 3 kinds of optical isomers, and is promptly left-handed, dextrorotation and raceme.The L-carnitine claims carnitine again, chemistry L-beta-hydroxy-gamma by name-trimethylammonium butanoic acid [(CH 3) 3-N +-CH 2-CHOH-CH 2-COO -], be a kind of safe and effective water-soluble amino acid.The L-carnitine is to human body and animal safety avirulence, and non-stimulated and mutagenicity is defined as nontoxic food additive by U.S. FDA and The World Health Organization (WHO).The latest report of at present relevant L-carnitine research think the L-carnitine have alleviate nervous, promote cardiovascular patient rehabilitation, enhancing immunity, acceleration protein synthesis, promote wound healing, protection cell membrane stability etc.
Conjugated linoleic acid is a kind of emerging nutrient substance and functional compound.The earliest, be found in roast beef and milk, but ignored in early days because its content is very low.To the eighties in 20th century, scientists finds that the conjugated linoleic acid of picked-up sufficient dosage can effectively suppress tumorigenic effect, thereby has caused people's extensive concern.Discover in a large number that afterwards CLA has anticancer, blood fat reducing, atherosclerosis, blood pressure lowering, enhancing human body immunity power and promotes important physical activity such as growth promoter, wherein the fat-reducing of conjugated linoleic acid and effect for reducing blood fat are especially favored.Studies have shown that CLA suppresses the synthetic of fat as the nutrition reallocation factor, the accent of induced lipolysis cell is died to wait and is reduced animal body fat.1994, Lee etc. (ConjugatedIinoleic acid, a new recognized nutrient Parisa MN) discovered that 0.5% CLA can significantly reduce the mice body fat, and increased the amount of lean meat.
At present, the application about conjugated linoleic acid and L-carnitine generally is to take respectively.Though Chinese patent CN1349795A discloses a kind of scheme of the compound preparation that is used for human body weight-losing by the preparation of conjugated linoleic acid and L-carnitine, but, because conjugated linoleic acid is a grease, and L-carnitine is a decorating film, in its patent, do not implement its real compound preparation, so-called compound preparation is that conjugated linoleic acid is made soft capsule and L-carnitine is made hard capsule in the patent, and human body is taken this two kinds of products simultaneously.And patent also only discloses its product and can be used for human body weight-losing.In order to overcome the deficiency of above-mentioned patent, the present invention is a kind of compound preparation of exploitation, and existing antiobesity action and the effect of blood fat reducing, blood sugar lowering, blood pressure lowering is arranged again also has the product of well preventing and treating the osteoporosis effect.
Summary of the invention
The purpose of this invention is to provide a kind of fat-reducing, blood fat reducing, blood sugar lowering, blood pressure lowering, osteoporotic compound preparation of control of being used for.
Of the present invention provide be used for fat-reducing, blood fat reducing, blood sugar lowering, blood pressure lowering, the osteoporotic compound preparation of control, be to contain calcium conjugated linoleic acid and L-carnitine or calcium conjugated linoleic acid and L-carnitine derivant in compound preparation, calcium conjugated linoleic acid: L-carnitine or calcium conjugated linoleic acid: the weight ratio of L-carnitine derivant is 4: 1~8.
Foundation of the present invention is: the antiobesity action of conjugated linoleic acid (be called for short CLA) animal and human body obtained confirmation (Park Y.et al.Effect of conjugated linoleic acidon body composition in mice[J] .Lipids, 1997,32:853-858; West D.B.Conjugated linoleic acid rapidly reduces body fat contentin mice without affecting energy intake[J] .Am.J.Physiol.1999; 276:R1172-R1179; Yang Depo etc., calcium conjugated linoleic acid trophism improve the sarcous experimentation of human body, Chinese oil, 2006,31 (8); 45-47).But its mechanism of action is also in further studying, acquired result of study shows, CLA can play fat-reducing and antihyperglycemic by two kinds of mechanism, one: CLA can reduce the activity of the synthetic required enzyme of fatty acid, and increase the activity of the required enzyme of fatty acid oxidation simultaneously, deposit in vivo thereby suppress fat, promote the burning of fat, reduce the accumulation of fat; Its two: CLA can increase makes body heat production catabiotic uncoupling protein-2 expression, thereby increases the energy expenditure of body, corrects dump energy and too much is stored in fatty tissue with fatty form.
Calcium is again the necessary biological element of human body, in the human body calcium content 99% all in skeleton and tooth, remaining 1% is present in soft tissue, extracellular fluid and the blood of human body, brings into play the various effects of important adjusting human body physiological function.Modern medicine study proves, calcium deficiency can cause human physiological disorder, and then cause a series of serious diseases, as hypertension, atherosclerosis, coronary heart disease, lithangiuria and osteoporosis etc. are therefore, human body replenishes an amount of calcium and is very important, calcium conjugated linoleic acid also is a kind of new organic calcium chemical compound, calcium conjugated linoleic acid can be decomposed into conjugated linoleic acid and calcium in (human gastric juice's pH is between 1 to 3 usually) under the sour environment of human stomach, bring into play the physiological action of CLA and calcium ion respectively, therefore, calcium conjugated linoleic acid has the dual function of conjugated linoleic acid and calcium, and this is a kind of novel organic calcium chemical compound.
L-carnitine or L-carnitine derivant play a part crucial in the lipid metabolism process, calcium conjugated linoleic acid and L-carnitine or and the L-carnitine derivant exist close metabolism dependency, the two is showing collaborative or complementary effect aspect the drug activity in performance.As the oxidation of fatty acids of energy substrate, need to carry out in Intramitochondrial β-district, fatty acid needs a kind of special transport mechanism that acyl COA is transported to beta oxidation degraded areas (in the mitochondrial matrix) because of can not directly penetrating mitochondrial inner membrane.On the one hand, long-chain fatty acid is being carried by carnitine and is being passed mitochondrial inner membrane in activatory, at first, fatty acid is by synzyme activation formation acyl coenzyme A, under the effect of the transferring enzyme in the film outside, be converted into fatty acyl carnitine and move in the film effect of the transferring enzyme in film again, slough carnitine and be transformed into acyl coenzyme A again, carnitine is unique carrier in this course; On the other hand, conjugated linoleic acid can increase the activity of carnitine palmitoyl based transferase, promotes the burning of fat.In addition.Calcium conjugated linoleic acid can also be by lowering lipidosis, promoting adipose cell to transfer the approach of dying to play complementary effect.
Calcium conjugated linoleic acid is very important for human body.Everyone every day, needed conjugated linoleic acid was equivalent to 2% to 4% of calorie uptake every day.Yet people's health can't produce this fatty acid of conjugated linoleic acid naturally, so we must replenish the absorption conjugated linoleic acid from the external world.Because conjugated linoleic acid is the fatty acid that contains a pair of unsaturated conjugated pair of key, this increases muscle to reducing body fat, and blood fat reducing, prevents that atherosclerosis and diabetes, cancer-resisting from playing an important role at mediator's immune function.And can be by accelerated combustion fat, suppress that adipose cell duplicate, ripe and fat storage minimizing body fat.
The present invention unites use with calcium conjugated linoleic acid and L-carnitine, makes them play synergic effect aspect the performance drug activity.
Calcium conjugated linoleic acid is to be synthesized into by conjugated linoleic acid and calcium chloride, is open and commercially available product is arranged.
Calcium conjugated linoleic acid is the general name of 18 carbon conjugated dienes acid calcium, can comprise one or more 9, the cis of 11-and 10,12 octadecadienoic acids and the calcium salt of transisomer conjugated linoleic acid.The calcium conjugated linoleic acid has here comprised along 9, anti-11-octadecadienoic acid calcium (c9, the t11-calcium conjugated linoleic acid) or anti-10, along 12-octadecadienoic acid calcium (t10, the c12-calcium conjugated linoleic acid) or mainly contain along 9, anti-11-octadecadienoic acid calcium (c9, the t11-calcium conjugated linoleic acid) and anti-10, along 12-octadecadienoic acid calcium (t10, the c12-calcium conjugated linoleic acid) mixture of two kinds of chemical compounds, and the content of these chemical compounds (single component or its mixture) surpasses 60% (percentage by weight).
L-carnitine exists with the form of free or derivant, its derivant has acetyl-L-carnitine, propionyl levo-carnitine, the hydrochloric acid L-carnitine, tartaric acid L-carnitine and other edible derivant, with acetyl-L-carnitine, propionyl levo-carnitine, hydrochloric acid L-carnitine, tartaric acid L-carnitine are good.
L-carnitine and derivant thereof are obtained by chemical synthesis process or biological synthesis method, and there is supply of commodities the domestic and international market at present, and this patent requires the purity of L-carnitine and derivant thereof more than 80%.
Because calcium conjugated linoleic acid is easily oxidized, for quality and the stability that guarantees product, can in compound preparation, add antioxidant, the use amount of antioxidant is 0.01~0.04% of a compound preparation gross weight, and adoptable here antioxidant is preferably one or more composite antioxidants in tea polyphenols or green tea extract (being called for short TPP) or Herba Rosmarini Officinalis extract or vitamin E or tert-butyl hydroquinone (being called for short TBHQ) or Butylated hydroxyanisole (BHA) or dibenzylatiooluene (being called for short BHT) or these compositions.
The said compound preparation of the present invention, can be prepared into multiple peroral dosage form, because of calcium conjugated linoleic acid and L-carnitine or L-carnitine derivant are solid, preferably be advisable to make solid oral dosage form, add different adjuvants, adopt conventional production process, promptly can be made into hard capsule, tablet, granule or powder etc.As food applications, the adjuvant of interpolation is good based on milk or milk powder to make milk sheet or milk powder.
Compound preparation provided by the present invention, its fat-reducing, blood fat reducing, blood sugar lowering, blood pressure lowering and prevent and treat the osteoporosis effect and verify through effect experiment, effect than calcium conjugated linoleic acid separately on probation or L-carnitine or L-carnitine derivant is better, and the two is showing collaborative or complementary effect aspect the performance drug activity to prove compound preparation.Experimental technique and result are as follows:
1. fat-reducing, blood fat reducing, hypoglycemic activity
1.1 laboratory animal:
70 of healthy SD male rats, body weight 70-90g.
1.2 experiment reagent:
Calcium conjugated linoleic acid, white or pale yellow powder, sample 15g are scattered in 100mL 1.5% carboxymethyl cellulose aqueous solution; L-carnitine, white crystal, sample 5g are dissolved in 100mL 1.5% carboxymethyl cellulose aqueous solution; A. calcium conjugated linoleic acid 15g and L-carnitine 5g (3: 1) are scattered in 100mL 1.5% carboxymethyl cellulose aqueous solution; B. calcium conjugated linoleic acid 16g and L-carnitine 4g (4: 1) are scattered in 100mL 1.5% carboxymethyl cellulose aqueous solution; C. calcium conjugated linoleic acid 7g and L-carnitine 14g (1: 2) are scattered in 100mL 1.5% carboxymethyl cellulose aqueous solution.
1.3 high lipid food prescription:
Normal feedstuff (the AIN-93G formulated of recommending form isozygoty into feedstuff) 73.8%, Adeps Sus domestica 10%, yolk powder 10%, sucrose 5%, cholesterol 1%, cholate 0.2% according to U.S. NNFA
1.4 experimental technique:
Rat is divided into 7 groups at random by body weight, is respectively blank group (NC), model control group (MC), calcium conjugated linoleic acid group (CLA-Ca), a.3 L-carnitine group (CAR) and calcium conjugated linoleic acid+L-carnitine group (fills a prescription: 1; Fill a prescription b.4: 1; Fill a prescription c.1: 2).Wherein the blank group gives normal feedstuff and freely ingests, and irritates stomach with 1mL/100g body weight 1.5% carboxymethyl cellulose aqueous solution per os simultaneously; Model control group, calcium conjugated linoleic acid group, L-carnitine group and calcium conjugated linoleic acid+L-carnitine group gives high lipid food free diet, irritate stomach with 1mL/100g body weight 1.5% carboxymethyl cellulose aqueous solution, the corresponding thing solution per os that tried of 1mL/100g body weight respectively simultaneously, tested 45 days.Experimental session record rat give appetite, surplus appetite and berley amount, calculate efficiency of food conversion, regularly weigh weekly 1 time.
Test the 40th day rat fasting 12h, measure fasting blood sugar, after the administration behind the 2h except that the blank group is irritated the stomach normal saline, all the other each groups are irritated stomach glucose solution 1g/kg body weight.Give sugar back 30,60min and 120min measure tail vein sugar value.
The rat fasting was 12 hours when experiment finished, weigh, etherization, eye socket is got blood and is surveyed blood fat (T-CHOL TC, triglyceride TG, HDL-C HDL-C, low-density lipoprotein cholesterol LDL-C), cut open the belly and get body fat pad (testis and perirenal fat pad) and weigh calculating fat body ratio.
1.5 experimental result
Each given the test agent of table 1 is to the influence of rat body weight
Grouping Starting weight g The heavy g in end Weightening finish g Food intake total amount g Efficiency of food conversion
NC MC CLA-Ca CAR prescription a prescription b prescription c 82±5 82±6 81±6 79±5 80±7 81±7 82±6 293±27 322±11 291±39 * 290±23 * 273±32 ** 285±33 * 280±26* 211±26 * 241±9 210±36 * 211±19 * 193±17 ** 204±21 * 198±23** 861 806 822 781 742 820 765 0.245 0.299 0.256 0.271 0.261 0.249 0.259
*Compare p<0.05 with model group; *Compare p<0.01 with model group
Each given the test agent of table 2 is to the influence of rat fat weight
Grouping The heavy g of fat The fat body compares %
NC MC 4.88±1.38 ** 12.44±4.70 1.65±0.43 ** 3.89±1.54
CLA-Ca CAR prescription a prescription b prescription c 7.58±2.67 ** 8.68±2.18 * 6.56±2.59 ** 7.78±3.06** 7.21±2.84** 2.65±0.92 * 2.92±0.58 2.36±0.84 ** 2.73±1.15* 2.56±1.22*
*Compare p<0.05 with model group; *Compare p<0.01 with model group
Each given the test agent of table 3 is to the influence of rat fat
Grouping TC(mmol/L) TG(mmol/L) HDL-C(mmol/L) LDL-C(mmol/L)
NC MC CLA-Ca CAR prescription a prescription b prescription c 2.36±0.29 ** 3.63±1.02 2.94±0.36 * 3.12±0.58 2.76±0.46 ** 3.08±0.44 2.89±0.71 * 0.75±0.14 ** 1.47±0.53 0.96±0.34 ** 0.83±0.37 ** 0.77±0.08 ** 0.93±0.22 ** 0.99±0.31 ** 1.30±0.13 1.45±0.44 1.38±0.48 1.68±0.36 1.54±0.30 1.93±0.38 * 1.50±0.52 0.44±0.12 ** 1.08±0.64 0.75±0.22 * 0.56±0.16 ** 0.58±0.20 ** 0.62±0.06 ** 0.77±0.23 *
*With model control group ratio, p<0.05; *With model control group ratio, p<0.01
Each given the test agent of table 4 is to the influence of rat carbohydrate tolerance
Group Blood glucose (mmol/L)
0min 30min 60min 120min
NC MC CLA-Ca CAR prescription a prescription b prescription c 5.31±0.91 6.28±1.46 5.03±1.22 6.05±1.61 4.63±1.11 * 5.15±1.31 5.62±1.75 5.64±0.89 ** 13.59±1.93 10.21±1.56 * 11.34±1.78 9.73±1.05 ** 9.62±1.23 ** 10.60±1.37 * 5.55±0.66 ** 11.32±1.77 9.16±1.02 9.53±1.46 8.39±1.39 * 8.74±1.11 * 9.37±1.54 5.49±0.75 ** 9.54±1.32. 7.74±0.87 * 8.31±1.45 6.61±1.06 * 7.25±1.37 * 7.46±1.29 *
*Compare p<0.05 with model group; *Compare p<0.01 with model group
By table 1 and table 2 as can be known, calcium conjugated linoleic acid and L-carnitine all can suppress the excessive increase because of the high fat diet rat body weight, minimizing body fat content (p<0.05), and they all have certain antiobesity action.But, also as can be seen, both unite use, can reduce body weight and the body fat content (p<0.01) of rat extremely significantly, illustrate that calcium conjugated linoleic acid and L-carnitine unite the effect that fat-reducing can be fast and effeciently played in use, its effect is stronger than using calcium conjugated linoleic acid or L-carnitine separately, and both ratios are that 3: 1 o'clock effects are better.
As shown in Table 3, calcium conjugated linoleic acid is united use with L-carnitine more can significantly reduce serum total cholesterol level than both independent uses, simultaneously also can substantial reduction in triglycerides and low-density lipoprotein cholesterol level, and both ratios are that 3: 1 o'clock effects are better.
As shown in Table 4, each given the test agent particularly prescription group can significantly reduce the rat fasting blood-glucose level, and each given the test agent group has resistant function to the blood sugar increasing that exogenous glucose causes when 30min, and onset is very fast.Prescription is organized particularly a group still can resist the blood sugar increasing that exogenous glucose causes when 60min and 120min, illustrating that calcium conjugated linoleic acid and L-carnitine unite to use more can significantly bring into play hypoglycemic activity than both independent uses, and both ratios are that 3: 1 o'clock effects are better.
The above results shows that compound preparation of the present invention had both been given full play to effect separately, can increase population effect again simultaneously, both can prevent and treatment of obesity, and blood fat reducing and blood sugar lowering can play resisting fatigue again, improve effects such as immunity, growth encourage.
2. prevent and treat the osteoporosis effect
2.1 laboratory animal:
40 of healthy male Balb/c mices, body weight 23-27g.
2.2 experiment reagent:
A. calcium conjugated linoleic acid 15g and L-carnitine 5g (3: 1) are scattered in the 100mL1.5% carboxymethyl cellulose aqueous solution; B. calcium conjugated linoleic acid 16g and L-carnitine 4g (4: 1) are scattered in the 100mL1.5% carboxymethyl cellulose aqueous solution; C. calcium conjugated linoleic acid 7g and L-carnitine 14g (1: 2) are scattered in the 100mL1.5% carboxymethyl cellulose aqueous solution.
2.3 experimental technique:
Rat is divided into 4 groups at random by body weight, is respectively blank group, calcium conjugated linoleic acid+L-carnitine group (prescription a.3: 1; Fill a prescription b.4: 1; Fill a prescription c.1: 2).Four groups all give normal feedstuff and freely ingest, and wherein the blank group is irritated stomach with 0.1mL/10g body weight 1.5% carboxymethyl cellulose aqueous solution per os; Calcium conjugated linoleic acid+L-carnitine group is tried thing solution per os with the 0.1mL/10g body weight and is irritated stomach, tests for 14 weeks.
The rat fasting was 12 hours when experiment finished, and weighed, and disconnected neck is put to death animal.Separate the left side femur, adopt dual intensity X line borne densitometers to measure its density.
2.4 experimental result
Experimental result sees Table 5.As seen from table, compound preparation of the present invention particularly both ratios is the femur density that can significantly reduce the body weight of mice at 3: 1 o'clock and increase mice, further verifies the antiobesity action of this compound preparation, can increase bone density again simultaneously, prevents and treats osteoporosis.
Table 5 given the test agent is to the influence of mice bone density
Grouping Body weight (g) Bone density (g/cm 2)
Before After
Matched group prescription a assembly side b assembly side c group 25.6±0.6 24.7±0.4 25.0±1.0 25.0±0.7 34.7±0.4 30.1±0.4 * 31.2±0.7* 30.4±1.2* 0.3358±0.0100 0.4021±0.0200 * 0.3855±0.0244* 0.3896±0.0176*
*With matched group ratio, p<0.05.
3. product provided by the present invention carries out human clinical's checking
Compound preparation of the present invention is used by obesity is merged the three-hypers crowd the effect of human body, and experimenter group does not have any untoward reaction as a result.
Take off the hard capsule of face embodiment 1,50 routine experimenters are tried out observation, wherein the women is 20,30 of male, and the age is at 30-70 between year.Using method is 3 times for each person every day, and each 4 hard capsules continue three months.Observed result sees Table 6.
Table 6 compound preparation is to the influence of human body body weight, blood glucose, triglyceride and blood pressure
Index Before the treatment After the treatment P
Body weight (kg) 88±10 81±7 <0.01
T-CHOL (mmol/L) 6.68±1.04 5.53±0.90 <0.01
Fasting glucose (mmol/L) 8.39±2.53 6.81±1.92 <0.01
Blood pressure (mmHg) Systolic pressure 157±12 144±14 <0.01
Diastolic pressure 110±14 97±12 <0.01
Beneficial effect of the present invention: compound preparation provided by the present invention, preparation is simple, easily industrialized mass; Taking convenience, effect is remarkable, has the osteoporotic effect of fat-reducing, blood fat reducing, blood sugar lowering, blood pressure lowering and control simultaneously, and performance drug activity aspect shows calcium conjugated linoleic acid and L-carnitine is collaborative or complementary effect.
Further set forth technical scheme of the present invention below by embodiment
The specific embodiment
Embodiment 1, calcium conjugated linoleic acid hard capsule
Material weighing: calcium conjugated linoleic acid 1500g (contain along 9, anti-11-octadecadienoic acid calcium and anti-10 is along the weight percentage 85% of the isomers of 12-octadecadienoic acid calcium), L-carnitine 500g, tea polyphenols 0.3g, hyprolose 10g, microcrystalline Cellulose 10g, magnesium stearate 5g.
Load weighted calcium conjugated linoleic acid, L-carnitine, tea polyphenols, hyprolose and microcrystalline Cellulose mix homogeneously; put in the fluidised bed granulator and granulate, pellet moisture is less than 5%, 30 mesh sieve granulate; add magnesium stearate, the particles filled capsule behind the mixing promptly, every loading amount 250mg.Be grown up dosage: 3-4g/ days.
Embodiment 2, calcium conjugated linoleic acid hard capsule
Material weighing: calcium conjugated linoleic acid 50g, acetyl-L-carnitine 100g, THBQ 0.02g, hyprolose 0.7g, microcrystalline Cellulose 1.2g, magnesium stearate 0.5g.
Load weighted calcium conjugated linoleic acid, acetyl-L-carnitine, THBQ, hyprolose and microcrystalline Cellulose mix homogeneously; put in the fluidised bed granulator and granulate, pellet moisture is less than 5%, 30 mesh sieve granulate; add magnesium stearate, the particles filled capsule behind the mixing promptly, every loading amount 250mg.
Embodiment 3, calcium conjugated linoleic acid hard capsule
Material weighing: calcium conjugated linoleic acid 100g, L-carnitine tartrate 25g, vitamin E 0.03g, hyprolose 1g, microcrystalline Cellulose 1g, magnesium stearate 0.5g.
Load weighted calcium conjugated linoleic acid, L-carnitine tartrate, vitamin E, hyprolose and microcrystalline Cellulose mix homogeneously; put in the fluidised bed granulator and granulate, pellet moisture is less than 5%, 30 mesh sieve granulate; add magnesium stearate, the particles filled capsule behind the mixing promptly, every loading amount 250mg.
Embodiment 4, calcium conjugated linoleic acid hard capsule
Material weighing: calcium conjugated linoleic acid 100g, propionyl levo-carnitine 50g, Herba Rosmarini Officinalis extract 0.02g, vitamin E 0.04g, sucrose 5g, microcrystalline Cellulose 1g, magnesium stearate 0.5g.
Load weighted calcium conjugated linoleic acid; propionyl levo-carnitine; Herba Rosmarini Officinalis extract, vitamin E, sucrose and microcrystalline Cellulose mix homogeneously; put in the fluidised bed granulator and granulate; pellet moisture adds magnesium stearate less than 5%, 30 mesh sieve granulate; particles filled capsule behind the mixing promptly, every loading amount 250mg.
Embodiment 5, calcium conjugated linoleic acid hard capsule
Material weighing: calcium conjugated linoleic acid 100g (contain suitable-9, anti--11 calcium conjugated linoleic acid percent by weight 75%), L-carnitine hydrochloride 100g, tea polyphenols 0.02g, THBQ 0.04g, sucrose 5g, microcrystalline Cellulose 1g, magnesium stearate 0.5g.
Load weighted calcium conjugated linoleic acid, L-carnitine hydrochloride, tea polyphenols, THBQ; sucrose and microcrystalline Cellulose mix homogeneously are put in the fluidised bed granulator and are granulated, and pellet moisture is less than 5%, 30 mesh sieve granulate; add magnesium stearate, the particles filled capsule behind the mixing promptly, every loading amount 250mg.
Embodiment 6, calcium conjugated linoleic acid hard capsule
Material weighing: calcium conjugated linoleic acid 100g (contain trans-10, the weight content of suitable-12 calcium conjugated linoleic acids is 65%), L-carnitine 50g, tea polyphenols 0.03g, hyprolose 1g, microcrystalline Cellulose 1g, magnesium stearate 0.5g.
Load weighted calcium conjugated linoleic acid, L-carnitine, tea polyphenols, hyprolose and microcrystalline Cellulose mix homogeneously; put in the fluidised bed granulator and granulate, pellet moisture is less than 5%, 30 mesh sieve granulate; add magnesium stearate, the particles filled capsule behind the mixing promptly, every loading amount 250mg.
Embodiment 7, conjugated linoleic acid calcium tablet
Material weighing: calcium conjugated linoleic acid 200g, L-carnitine 50g, the fragrant extract 0.04g of Herba Rosmarini Officinalis, starch 100g, hyprolose 1g.
Load weighted calcium conjugated linoleic acid, the L-carnitine, the fragrant extract of Herba Rosmarini Officinalis, starch and hyprolose mix homogeneously, with the tablet machine tabletting, pack, every 250mg.Be grown up dosage: 3-4g/ days.
Embodiment 8, conjugated linoleic acid calcium tablet
Material weighing: calcium conjugated linoleic acid 50g, L-carnitine hydrochloride 100g, TPP 0.01g, starch 100g, microcrystalline Cellulose 1g.
Load weighted calcium conjugated linoleic acid, the L-carnitine hydrochloride, TPP, starch and microcrystalline Cellulose mix homogeneously, with the tablet machine tabletting, pack, every 250mg.
Embodiment 9, conjugated linoleic acid calcium tablet
Material weighing: calcium conjugated linoleic acid 60g (containing trans-10, suitable-12 calcium conjugated linoleic acid percent by weight 60%), L-carnitine 100g, vitamin E 0.01g, starch 100g, microcrystalline Cellulose 1g.
The weighing calcium conjugated linoleic acid, the L-carnitine, vitamin E, starch and microcrystalline Cellulose mix homogeneously, with the tablet machine tabletting, pack, every 250mg.
Embodiment 10, calcium conjugated linoleic acid film coating tablet
Material weighing: calcium conjugated linoleic acid 150g, L-carnitine 50g, tea polyphenols 0.03g, starch 100g, microcrystalline Cellulose 2g, magnesium stearate 0.5g.
Load weighted calcium conjugated linoleic acid, the L-carnitine, tea polyphenols, starch and microcrystalline Cellulose mix homogeneously, the plain sheet of tablet technology tabletting system routinely, reuse 3%HPMC carries out film coating, makes film coating tablet.
Embodiment 11, calcium conjugated linoleic acid film coating tablet
Material weighing: calcium conjugated linoleic acid 50g (containing trans-10, suitable-12 calcium conjugated linoleic acid percent by weight 70%), acetyl-L-carnitine 100g, THBQ 0.04g, starch 100g, microcrystalline Cellulose 2g, magnesium stearate 0.5g.
Load weighted trans-10, suitable-12 calcium conjugated linoleic acids, acetyl-L-carnitine, THBQ, starch and microcrystalline Cellulose mix homogeneously, the plain sheet of tablet technology tabletting system routinely, reuse 3%HPMC (containing 1% titanium dioxide) carries out film coating, makes film coating tablet.Be grown up dosage: 2.5-3.5g/ days.
Embodiment 12, calcium conjugated linoleic acid powder
Material weighing: calcium conjugated linoleic acid 50g, L-carnitine 100g, tea polyphenols 0.01g.
Load weighted calcium conjugated linoleic acid, the L-carnitine, the tea polyphenols mix homogeneously is crushed to 150~200 orders, adopts waterproof, lucifuge, free of contamination packaging material to pack every bag of 1g.Be grown up dosage: 3-4g/ days.
Embodiment 13, calcium conjugated linoleic acid granule
Material weighing: calcium conjugated linoleic acid 150g, L-carnitine 50g, tea polyphenols 0.04g, microcrystalline Cellulose 1g.
Load weighted calcium conjugated linoleic acid, the L-carnitine, tea polyphenols and microcrystalline Cellulose mix homogeneously are granulated with 5%PVP ethanol liquid, drying, granulate adopts waterproof, lucifuge, free of contamination packaging material to pack every bag of 1g.Be grown up dosage: 3-4g/ days.
Embodiment 14, conjugated linoleic acid calcium dried milk
Material weighing: defat fresh milk 10L, conjugated linoleic acid 150ml (2.5%V/V), calcium conjugated linoleic acid 100g (0.3%M/V), L-carnitine 40g (0.3%M/V) vitamin A 0.03g, vitamin D 0.0002g.
Load weighted calcium conjugated linoleic acid, carnitine, vitamin A, D are mixed with conjugated linoleic acid, and milk is heated to 40-45 ℃, and mixture is added in the defat fresh milk, stirs, and homogenizing once under 35-40Mpa pressure.After 85 ℃ of sterilizations in short-term, be controlled at 160-165 ℃ with inlet temperature, the condition that leaving air temp is controlled at about 75-80 ℃ is carried out spray drying, adopts waterproof, lucifuge, free of contamination packaging material to pack.Be grown up dosage: 6-10g/ days.
The conjugated linoleic acid calcium dried milk that embodiment 15, baby encourage
Material weighing: full-cream fresh milk 10L, grip glyceryl linoleate 24ml (0.3%V/V) altogether, calcium conjugated linoleic acid 10g (0.1%M/V), carnitine 6g (M/V) arachidonic acid 5g, EPA and DHA are 2g, vitamin A, vitamin D, vitamin E are respectively 0.02g, 0.0001g, 0.05g, and lecithin is 5g.
Load weighted calcium conjugated linoleic acid, carnitine, arachidonic acid, EPA, DHA, lecithin, vitamin A, D, E are gripped glyceryl linoleate together to be mixed, milk is heated to 50 ~ 55 ℃, mixture is joined in the full-cream fresh milk, stir, ultrasonic homogenizing is 5 minutes under the 80kHz frequency.After 85 ℃ of sterilizations in short-term, be controlled at 160 ~ 165 ℃ with inlet temperature, the condition that leaving air temp is controlled at about 75-80 ℃ is carried out spray drying, adopts waterproof, lucifuge, free of contamination packaging material to pack.Dosage: 3-4g/ days.
Embodiment 16, CLA milk calcium tablet
Calcium conjugated linoleic acid 16%, L-carnitine 8%, glucose powder 15%, cane sugar powder 25%, starch 8%, citric acid 0.5%, surplus are the full-cream of CLA or half fat milk powder.Behind all raw material mix homogeneously, with the tablet machine tabletting, every 500mg, pack.Be grown up dosage: 8-12g/ days.

Claims (7)

1. one kind is used for fat-reducing, blood fat reducing, blood sugar lowering, blood pressure lowering, the osteoporotic compound preparation of control, it is characterized in that containing in the compound preparation calcium conjugated linoleic acid and L-carnitine or calcium conjugated linoleic acid and L-carnitine derivant, calcium conjugated linoleic acid: L-carnitine or calcium conjugated linoleic acid: the weight ratio of L-carnitine derivant is 4: 1~8.
2. described compound preparation according to claim 1, it is characterized in that said calcium conjugated linoleic acid is to contain along 9, anti-11-octadecadienoic acid calcium and/or anti-10, isomers along 12-octadecadienoic acid calcium, contain in its calcium conjugated linoleic acid along 9, anti-11-octadecadienoic acid calcium and/or anti-10 surpasses 60% along the weight percentage of the isomers of 12-octadecadienoic acid calcium.
3. described compound preparation according to claim 1 is characterized in that said L-carnitine derivant is an acetyl-L-carnitine, propionyl levo-carnitine, hydrochloric acid L-carnitine, tartaric acid L-carnitine.
4. compound preparation according to claim 1 is characterized in that: also contain antioxidant in this compound preparation, the consumption of antioxidant is 0.01~0.04% of a compound preparation gross weight.
5. compound preparation according to claim 4, it is characterized in that: said antioxidant is tea polyphenols or green tea extract or Herba Rosmarini Officinalis extract or vitamin E or tert-butyl hydroquinone or Butylated hydroxyanisole or dibenzylatiooluene, adopts wherein one or more.
6. compound preparation according to claim 1 is characterized in that: said compound preparation is tablet, capsule, powder, granule.
7. compound preparation according to claim 6 is characterized in that: said compound preparation is that tablet is the milk sheet, and said powder is milk powder.
CNB2007100283744A 2007-06-01 2007-06-01 Be used for fat-reducing, blood fat reducing, blood sugar lowering, blood pressure lowering, the osteoporotic compound preparation of control Expired - Fee Related CN100539999C (en)

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CN102018832A (en) * 2010-11-16 2011-04-20 北京康比特体育科技股份有限公司 Weight-reducing composition and preparation method thereof
CN102188565A (en) * 2011-04-09 2011-09-21 荣成百合生物技术有限公司 Weight-losing soft capsules and preparation method thereof
CN104146263A (en) * 2014-08-15 2014-11-19 江西维莱营健高科有限公司 Weight reducing soft capsule and preparation method thereof
CN107625914A (en) * 2017-10-16 2018-01-26 唐宏泉 A kind of cosmetic slimming nutrition and health care capsule and preparation method thereof
WO2019034112A1 (en) * 2017-08-17 2019-02-21 博瑞生物医药(苏州)股份有限公司 COMPOSITION CONTAINING L-CARNITINE AND β-HYDROXYBUTYRATE COMPOUND
CN110433254A (en) * 2018-05-04 2019-11-12 李新华 A kind of milk piece shape solid content preparing balancing blood pressure with mother-of-pearl compound

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US4537772A (en) * 1984-05-02 1985-08-27 Merck & Co., Inc. Enhancing absorption of drugs from gastrointestinal tract using acylcarnitines
CN1349795A (en) * 2000-10-19 2002-05-22 珠海威尔发展有限公司 Compound slimming prepn and its application
CN1159281C (en) * 2002-05-31 2004-07-28 国家海洋局第一海洋研究所 Composition containing conjugated calcium linoleate and making method thereof

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CN102018832A (en) * 2010-11-16 2011-04-20 北京康比特体育科技股份有限公司 Weight-reducing composition and preparation method thereof
CN102018832B (en) * 2010-11-16 2013-05-29 北京康比特体育科技股份有限公司 Weight-reducing composition and preparation method thereof
CN102188565A (en) * 2011-04-09 2011-09-21 荣成百合生物技术有限公司 Weight-losing soft capsules and preparation method thereof
CN102188565B (en) * 2011-04-09 2012-05-30 荣成百合生物技术有限公司 Weight-losing soft capsules and preparation method thereof
CN104146263A (en) * 2014-08-15 2014-11-19 江西维莱营健高科有限公司 Weight reducing soft capsule and preparation method thereof
WO2019034112A1 (en) * 2017-08-17 2019-02-21 博瑞生物医药(苏州)股份有限公司 COMPOSITION CONTAINING L-CARNITINE AND β-HYDROXYBUTYRATE COMPOUND
CN107625914A (en) * 2017-10-16 2018-01-26 唐宏泉 A kind of cosmetic slimming nutrition and health care capsule and preparation method thereof
CN110433254A (en) * 2018-05-04 2019-11-12 李新华 A kind of milk piece shape solid content preparing balancing blood pressure with mother-of-pearl compound

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