CN107998220A - It is a kind of to be used to reduce food intake, delay hunger, the composition of control body weight - Google Patents
It is a kind of to be used to reduce food intake, delay hunger, the composition of control body weight Download PDFInfo
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Classifications
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- 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)
- A61K36/82—Theaceae (Tea family), e.g. camellia
-
- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Abstract
The present invention relates to it is a kind of be used for reduce food intake, delay hunger, body weight control composition, specifically, the composition is that compatibility forms according to a certain percentage by tea flower extract and line leaf goldspink flower extract.Said composition can inhibit neuropeptide tyrosine and AGRP mRNA level in-sites, achieve the purpose that to reduce food intake, delay hunger, control body weight, in particular for reducing the food-intake of metabolic disorder Disease caused by fat or obesity, it can be used as oral drugs, health food, special medicine purposes formula food or the function nutrition food of body weight control management.
Description
Technical field
It is particularly a kind of to suppress neuropeptide tyrosine/agouti peptide gene GAP-associated protein GAP by cooperateing with the present invention relates to a kind of composition
(AGRP) mRNA hormonal readinesses are secreted, and have the function that to reduce food intake, delay hunger, the composition of control body weight, can
Prevention and treatment for metabolic disorder disease caused by fat and obesity.
Background technology
With the change of human diet structure and eating habit, the generation of metabolic disorder disease caused by fat and obesity
Rate increasingly increases.Regrettably, overweight people is not inadequate to the continence of cuisines, but helplessly look at and oneself become day by day
It is fat.We one day 24 it is small when all face same cuisines, why stature is differentIt is more that we suggest that overweight people eats less always
Movement, but this method is not proved effective really.
The mankind are in the long-term energy balance regulating system with foring complexity in hungry struggle, its caloric intake and storage energy
Power will be far longer than energy consumption function.In the modern times of material extreme enrichment, this energy balance mechanism makes the mankind be absorbed in obesity
Puzzlement.Data shows that weight is controlled by gastrointestinal hormone in human body.Hormonal readiness influence hunger, also with brain sense
Know that the region of pleasure is connected.Obese patient becomes fat truth and is the stomach satiety/secretion of hunger hormonal readiness is unbalance, it is old starve it is total
It does not have enough to eat, diet is out of control, finally becomes fat.It should be noted that only by simply reducing food intake, food quickly by
Digestion, can feel hungry, brain can send signal of ingesting again quickly after edible.As it can be seen that " regulation and control correlation is ingested hormone secretion water
It is flat, reduce food intake, postpone hunger " become the most strong breakthrough scheme of mankind's combating obesity.Regrettably, safety
It is also less at present effective for the composition of regulation and control gastrointestinal hormone level, reduction food intake, delay hunger.
Related neural peptide hormone of particularly being ingested based on gastrointestinal hormone is horizontal, has been risen very during fat occurrence and development
Big effect, therefore study their effects in fat pathogenesis, particularly reduce food intake, delay hunger,
In terms of control body weight, can be metabolic disorder disease caused by obesity and obesity prevention and treatment provide certain science according to
According to and means of prevention.Antagonism is ingested the expression of related neural peptide hormone level, also just becoming that treatment is fat and obesity caused by generation
Thank to the novel targets of disorder disease.
More and more results of study show that hypothalamus energy balance dysregulation is probably the fat middle important department formed
System, it should be noted that related neural peptide hormone level of ingesting, wherein the neuropeptide tyrosine by the same neurons secrete of its arcuate nucleus
(NPY)/agouti peptide gene GAP-associated protein GAP (AGRP) hormone, has the function that to whet the appetite, suppresses energy expenditure.
Neuropeptide tyrosine (neuropeptide Y, NPY) is a kind of maincenter and widely distributed 36 amino acid of peripheral neverous system
Polypeptide, is a kind of intense stimulus thing of food intake, is one of most potent rush food neuropeptide hormone, increase NPY levels can be led
Cause excessive food intake.Research shows that NPY hormonal readinesses influence body nutritional status in hypothalamus, is that energy balance is adjusted for a long time
One key factor of section.NPY is higher in the concentration of hypothalamus, mainly by the neurons secrete of arcuate nucleus (ARC), this neuron
Projection extends to nucleus paraventricularis and back nuclear, the two contains abundant NPY immune response nerve endings.In hungry, diabetes and play
Under strong motion state, NPY can stimulate the efficient storage ingested with energy, be mainly manifested in that diet is hyperfunction and brown adipose tissue production
Heat is reduced, this has great importance for recovering energy balance and existence.Therefore adjusting of the NPY neurons to energetic supersession can
It can be that they can substantially experience the reduction of body energy storage, and be ingested by stimulation and weaken heat production to recover energy balance.
The activation of verified neuropeptide tyrosine Y5 acceptors causes bulimia nervosa, therefore NPY Y5 receptor antagonists can be used for treating bulimia nervosa
Caused obesity, can promote weight loss or prevent weight gain.
Agouti peptide gene GAP-associated protein GAP (Agouti gene related protein, AGRP) is residual by 50 amino acid
The polypeptide of base composition.Moussa etc. has found a kind of ground squirrel, produces obesity due to the gene mutation of agouti peptide (Agouti), at the same time
It is associated with the symptoms such as high feed, insulin resistance, hyperglycaemia.Agouti is a kind of peptide hormone produced by hair follicle cell, is had
Play the role of suppressing to cause chromatophore to produce melanin by α-MSH.α-MSH have inhibitory action to feed, are maincenter casting skin matter
The endogenic ligand of plain acceptor (melanocortine receptor, MCR).Agouti mainly acts on MC1 acceptors and plays resistance
Disconnected effect, AGRP mainly express the compatibility for having height to MC3R and MC4R at the middle part of nucleus arcuatus hypothalami (ARC), be α-
The competitive antagonist of MSH.The expression increase of AGRP mRNA fasting states；It is overexpressed the transgenic mice obesity but skin of AGRP
Color not change；Intracerebroventricular AGRP can make mouse feed and weight gain, and be in dose-effect relationship.
Although NPY and AGRP is all eating signal, their mechanism of action but differs.NPY is directly sent out by npy receptor
The effect of waving, and AGRP is mainly by competitive binding melanocortin stimulating acceptor MC3R and MC4R, so that the effect of antagonism α-MSH.
Since NPY and AGRP is by the same neuron generations of ARC, can influence NPY synthesis and the factor of release can similarly influence AGRP.For
This, suppressing NPY/AGRP mRNA expression is also just becoming reduction food intake, delay hunger, the new target of control body weight concern
Point.
Tea Flower (Tea blossom) is Theaceae Camellia tea tree Camellia sinensis (L.) O.Kuntze
Flower, original producton location China, is planted in Chinese middle and south each province, is approved as new raw-food material by the Ministry of Public Health on January 4th, 2013 extensively
(Ministry of Public Health announce 2013 No. 1).Studies have found that tea flower extract has the function that control body weight, mainly with suppression
Pancreatic lipase activity suppression fat absorption, improvement fat metabolism suppression blood neutral fat level rise related.Patent CN
There is provided in 105685995 " a kind of compositions of weight-reducing " containing navy bean extract, tea flower extract, green-tea extract and
The composition of inulin, zoopery prove that composition can suppress the body weight increase of obese model rat, mitigate obese model rat
Body fat accumulation, reduce obese model rat food utilization, prompt said composition there is weight losing function, but the experiment
As a result prove that food ration and total amount of heat intake of the said composition to animal has no significant effect." one kind subtracts patent CN 104366468
Offer contains soybean protein isolate, milk protein, lactalbumin, water-soluble meals in fertilizer generation meal composition and preparation method thereof "
Eat the generation meal composition of fiber, tea flower extract, crystal diabetin and oligomeric maltose, the edible group of satiety test data prompting
Hunger reduces after compound, 5 it is small when after the highest rate that feels hungry be 12.32% (embodiment 6), wherein tea flower extract
0.62%, water-soluble dietary fiber is accounted for account for 17.8%, total protein 57.7% (soybean protein isolate accounts for 8.9%, milk protein-junket
Albumen accounts for 4.4%, lactalbumin and accounts for 44.4%)；5 it is small when after the minimum ratio that feels hungry be 6.31% (embodiment 2), wherein
Tea flower extract account for 0.18%, water-soluble dietary fiber account for 13.4%, total protein 58% (soybean protein isolate accounts for 22.3%,
Milk protein-casein accounts for 22.3%, lactalbumin and accounts for 13.4%).In the weight losing meal-replacing experiment of 30 days, embodiment 2 is put down
Equal weight loss 9kg, average body fat rate reduce by 6.22%；The average weight of embodiment 6 reduces 5kg, and body fat rate reduces by 2.69%.
Embodiment 1,3,4,5 groups, tea flower extract ratio accounts for 0.09%, 0.89%, 0.45%, 0.36% respectively, average weight point
Not Jiang Di 4.2kg, 2.9kg, 4.9kg, 3.2kg, average body fat rate reduces by 2.13%, 5%, 3.09%, 3.17% respectively.2
Human clinical trial's evidence prompts the ratio of tea flower extract and water-soluble dietary fiber in the composition to improve, to abdomen of satisfying
Sense, weight and body fat rate reduce not dose-effect dependent interaction expected from presentation, opposite soybean protein isolate and milk protein (junket egg
Ratio increase in vain), produces stronger satiety effect, and weight is significantly reduced with body fat rate, thus it is speculated that said composition produces loss of weight
Effect mainly cooperates with generation satiety related to soybean protein isolate with milk protein (casein).Thus illustrate, Tea Flower carries
Though taking thing to have the function that certain delay gastric emptying time, delay hunger, clinical test finds tea flower extract production
The effect of raw satiety, delay hunger, losing weight and body fat rate, cannot still meet the needs of preferable control body weight.
Line leaf broom top, the doctor's tea that is otherwise known as (Louis boss Rooibos or red shrubs tea), the pulse family from South Africa
(Leguminosae) plant (Classification system：Aspalathus Linearis (Brum.f.) R.Dahlgren), Leaf-feeding insects are
Leaf and thin stem, for edible way to brew, on June 26th, 2014 is approved as new raw-food material (2014 No. 12 by the Ministry of Public Health
Bulletin).Patent CN105248769 " a kind of preparation method of Louis boss tea instant powder " is mentioned, and Rooibos tea is free of coffee
Cause, rich in a variety of Flavonoid substances, modern pharmacological studies have shown that the tea to it is anti-oxidant, control diabetes and its complication, delay
Aging etc. has effect." it is applied to diabetes mellitus prevention and the plant extract composition of control " in patent CN104127594
Mention, Rooibos is rich in antioxidant, and polyphenol content is higher than green tea, and resists gene mutation, anticancer, anti-inflammatory and antiviral
With particular utility, animal experiment proves that contain dietary fiber, grape seed extract and South Africa black tea that the invention provides extract
The composition of thing, reduces fasting blood-glucose, 2h-plasma glucose effect significantly, but sugar tolerance value is reduced compared with model control group without aobvious
Write sex differernce.Mentioned in patent CN 101765433 " a kind of extract of rooibos of anti-diabetic ", red shrub tea, which has, to be alleviated
Symptom, its contained flavone compound such as insomnia, nervous, gastrospasm and allergy have strong anti-oxidation and radicals scavenging
Activity, and have anticancer, the potential of anti arteriosclerosis.The red shrub tea extract that the invention provides has control blood glucose effect,
Its active ingredient for flavone compound Aspalathin (3 '-C-f1-D- glucopyranosyls -2 ', 3,4,4 ', 6 '-penta hydroxy group
Dihydrochalcone), monkey animal experiment confirms that the red shrub tea extract 7d of oral 1-2.5mg/kg can effectively reduce inhuman spirit
Long class animal velvet monkey (Chlorocebus aethiops) blood glucose, it is seen that line leaf goldspink flower extract can be used for glycemic control.
Have no line leaf goldspink flower extract for fat any research and report.
The content of the invention
Modern is becoming more and more fat, our diet is very abundant, or even excessively rich, how to solve it is fat and
It is extremely urgent the problem of metabolic disorder type disease caused by obesity.The present inventor seminar is always with NPY/AGRP mRNA tables
It is target spot up to level, screening can suppress the expression of NPY/AGRP mRNA hormonal readinesses, there is collaboration to reduce food intake, prolong
Slow hunger, the plant extracts of control body weight or plant extract composition.Invention it has been surprisingly found that Tea Flower extracts
Thing can be cooperateed with effectively with line leaf goldspink flower extract suppresses the expression of NPY/AGRP mRNA hormonal readinesses, and there is collaboration to reduce
Food intake, the effect for postponing hunger, control body weight, are relatively used alone tea flower extract or line leaf goldspink flower extract
Show more excellent effect, so as to complete the present invention.
It is an object of the invention to provide it is a kind of reduce food intake, delay hunger, control body weight composition, be used for
Metabolic disorder type disease caused by prevention or treatment obesity and obesity.The pharmaceutical composition is by tea flower extract and line leaf goldspink
Flower extract compounds composition according to a certain percentage.
The composition of the present invention can cooperate with suppression neuropeptide tyrosine/agouti peptide gene GAP-associated protein GAP (AGRP) mRNA hormone water
Divide equally and secrete, have the function that to reduce food intake, delay hunger, control body weight.
Tea Flower of the present invention is the flower selected from Theaceae Camellia tea tree plant Camellia sinensis, and institute
It is pulse family (Leguminosae) plant (Classification system selected from South Africa to state line leaf broom top：Aspalathus Linearis
(Brum.f.) R.Dahlgren) leaf and thin stem.
In one embodiment of the invention, the composition is with tea flower extract and line leaf goldspink flower extract
For made of raw material, wherein tea flower extract and the part by weight of line leaf goldspink flower extract is 1-20:20-1.
In one embodiment of the invention, total saponin content is contained not less than 2.0% in the tea flower extract
Chakasaponin II are not less than 1.0%；General flavone content is contained not less than 2.0% in line leaf goldspink flower extract
Aspalathin is not less than 0.1%.
In one embodiment of the invention, the weight of the composition tea flower extract and line leaf goldspink flower extract
Amount ratio is preferably 1-5:5-1.
In one embodiment of the invention, the Tea Flower total saponin content is contained not less than 50.0%
Chakasaponin II are not less than 20.0%, and line leaf broom top general flavone content is not less than 50.0%, and contained Aspalathin is not
Less than 2%.
The measure of tea tree flower total saponine of the present invention, with from tea tree flower total saponine through column chromatography repeatedly separation and purification obtain it is pure
Spend 92%-98% Chakasaponin II (see Fig. 1, Fig. 2) be reference substance, according to those skilled in the art's conventional H PLC outside
Scalar quantity method (4.6 × 260mm of C18 chromatographic columns；Mobile phase：Methanol：Trifluoroacetic acid (65：35V/V)；Wavelength 230nm；Column temperature 40
℃；Flow velocity 1.0ml/min) detection, and with the content and tea flower extract of saponin(e peak gross area calculating tea tree flower total saponine
The content of contained Chakasaponin II；Line leaf broom top general flavone, using rutin as reference substance, according to those skilled in the art
Reference Conventional UV-visible ray photometry (measure of the total flavonoids in health food such as Jiang Yaping, physical and chemical inspection-chemistry fascicle,
2003,39(5):307-307；) detect and calculate the content of line leaf broom top general flavone, with from line leaf broom top general flavone through column
The chromatography Aspalathin that separation and purification obtains purity 92%-98% repeatedly is reference substance (see Fig. 4 and Fig. 5), according to this area skill
Art personnel are with reference to conventional H PLC gradient elutions and outer marking quantitative method (new resource food doctor's tea HPLC finger-prints such as Cha Shenghua
Research, R＆D of modern TCM and practice, 2010,24 (3)：69-71) detect and calculate institute in line leaf goldspink flower extract
Aspalathin contents.
It is a further object of the present invention to provide the preparation method of the composition of the present invention.In one embodiment of the present invention
In case, the preparation method includes extracting Tea Flower and line leaf broom top with the Extraction solvent for being selected from water and ethanol and pure
The step of change.
In one embodiment of the invention, after the preparation method specifically includes 1) Tea Flower crushing, with 6-15 times
The ethanol of the water of amount or various concentrations extracts 1-3 time, 25-100 DEG C of temperature, when each 0.5-24 is small, filters, merging filtrate, subtracts
Pressure concentration, pressure can be 1.2-25.5kpa, and temperature is 40-50 DEG C, or film concentration, and membrane aperture can be 0.2 μm, UF membrane
Film in processing in the NF membrane of 100~1000Dal, can retain tea tree flower total saponine, easy to separate using molecular cut off
Water, concentrates Tea Flower extracting solution, and the operating temperature in film concentration process is controlled less than 40 DEG C, prevent tea tree flower total saponine because of
It is subject to high fever and is destroyed；Spray drying, inlet air temperature can be 120-160 DEG C, and leaving air temp can be 70-100 DEG C, or cold
It is lyophilized dry, obtain tea flower extract；2) after line leaf broom top crushes, 1- is extracted with the ethanol of the 6-15 times of water measured or various concentrations
3 times, 25-100 DEG C of temperature, when each 0.5-24 is small, filtering, merging filtrate, is concentrated under reduced pressure, and pressure can be 1.2-25.5kpa,
Temperature is 40-50 DEG C, or film concentration, and membrane aperture can be 0.2 μm.Film in membrane separation is using molecular cut off 100
The NF membrane of~1000Dal, can retain line leaf broom top general flavone, and easy to separate water, enriching line leaf broom top general flavone carries
Take solution, the operating temperature in film concentration process is controlled less than 40 DEG C, prevents line leaf broom top general flavone because of being subject to high fever
And be destroyed), spray drying, inlet air temperature can be 120-160 DEG C, and leaving air temp can be 70-100 DEG C, or freeze-drying,
Dry line leaf goldspink flower extract；3) it is 1-20 according to part by weight by tea flower extract and line leaf goldspink flower extract:
20-1 after mixing, adds appropriate pharmaceutically acceptable auxiliary material and is uniformly mixed, to obtain the final product.
It is the new raw-food material of Ministry of Public Health's approval based on Tea Flower and line leaf broom top, edible way is to brew.Consider
To foodsafety, the function of being prepared using tea flower extract of the present invention and line leaf broom top extractive composition as raw material
Food preferred water extraction, and because of the decaffeinated component of line leaf goldspink flower extract, security is preferable, except suitable for adult,
It is applicable to the prevention and treatment of metabolic disorder type disease caused by the body weight control and obesity of Obese children.
In one embodiment of the invention, the preparation method of composition of the present invention is preferably as follows：1) Tea Flower
After crushing, extracted 1-3 times with the ethanol of the 8-12 times of water measured or various concentrations, 25-100 DEG C of temperature, when each 0.5-24 is small, mistake
Filter, merging filtrate, is concentrated under reduced pressure, and pressure can be 1.2-25.5kpa, and temperature can be 40-50 DEG C, or film concentration, membrane aperture
0.2 μm, film in membrane separation in the NF membrane of 100~1000Dal, can retain the total soap of Tea Flower using molecular cut off
Glycosides, easy to separate water or ethanol solution, concentrates tea flower extract solution, and the operating temperature in film concentration process is controlled at 40 DEG C
Hereinafter,.Tea tree flower total saponine is prevented to be destroyed because high fever is subject to, concentrate passes through the D-101 macropore trees anticipated
Fat column, is first washed with deionized water de-, discards eluent, after with 50-90% ethanol elutions, collects eluent, recycles ethanol, dry
Obtain tea flower extract；2) after line leaf broom top crushes, extracted 1-3 times with the ethanol of the 8-12 times of water measured or various concentrations, temperature
When 25-100 DEG C of degree, each 0.5-24 are small, filtering, merging filtrate, is concentrated under reduced pressure, and pressure can be 1.2-25.5kpa, and temperature can
Think 40-50 DEG C, or film concentration, membrane aperture are 0.2 μm, the film in membrane separation using molecular cut off 100~
The NF membrane of 1000Dal, can retain line leaf broom top general flavone, easy to separate water or ethanol solution, enriching line leaf broom top
Extract solution.Operating temperature in film concentration process is controlled below 40 DEG C, prevents line leaf broom top general flavone because being subject to
High fever and be destroyed), concentrate is first washed with deionized water de- by the AB-8 macroporous resin columns anticipated, discards elution
Liquid, after with 50-90% ethanol elutions, collects eluent, recycles ethanol, obtain line leaf goldspink flower extract；3) by the Tea Flower
Extract is 1-5 according to part by weight with line leaf goldspink flower extract:5-1 after mixing, is added appropriate pharmaceutically acceptable
Auxiliary material is uniformly mixed, to obtain the final product.
The preparation method of pharmaceutical composition of the present invention can use the conventional method of pharmaceutical field, use the medicinal auxiliary of routine
Material carries out.For example with conventional method by the tea flower extract compounded according to a certain percentage, line leaf goldspink flower extract with appointing
Acceptable carrier or auxiliary material mixing is commonly used in the one or more kinds of pharmacies of meaning, various peroral dosage forms are then made.It is described
Carrier such as diluent, anticaking agent.Specifically, the carrier such as resistant starch, maltodextrin, resistant dextrin, crystallite
Cellulose, hypromellose, superfine silica gel powder etc..As needed, using the composition of the present invention as active ingredient, addition can connect
Other raw materials and auxiliary material received, the medicine, health food, special medicine suitable for oral medication are prepared into galenic pharmacy routine techniques
Purposes formula food or function nutrition food formulation, can be following any formulations：Powder, granule, tablet, hard shell capsules
Agent, oral liquid, suspension etc., for reaching metabolic disorder type caused by prevention and treatment obesity and obesity by body weight control
The purpose of disease.
Brief description of the drawings
1 tea flower extract active ingredient Chakasaponin II chemical constitutions of attached drawing
2 Tea Flower saponin(e Chakasaponin II reference substance HPLC spectrograms of attached drawing, Detection wavelength 230nm, retention time are
37.856min。
The HPLC spectrograms of 3 embodiment of attached drawing, 1 tea flower extract 3, Detection wavelength 230nm, retention time 38.003min are
Chakasaponin II peaks.
4 line leaf goldspink flower extract active components A spalathin chemical constitutions of attached drawing
5 line leaf broom top extract A spalathin reference substance HPLC collection of illustrative plates of attached drawing, Detection wavelength 278nm, retention time
For 44.952.
The HPLC spectrograms of 6 embodiment of attached drawing, 2 line leaf broom top flower extract 3, Detection wavelength 278nm, retention time
44.998min it is Aspalathin peaks.
Embodiment
Embodiment 1：The preparation of tea flower extract
1) tea flower extract 1：After Tea Flower crushes, 3 times are extracted with 30 DEG C of the water of 15 times of amounts, every time 3 it is small when, centrifuged
Filter, merging filtrate, be concentrated under reduced pressure (12kpa, 45 DEG C) to density be 1.1g/ml, be spray-dried (140 DEG C of inlet air, 80 DEG C of outlet air,
70 DEG C of feed temperature), obtain tea flower extract 1.Using Chakasaponin II as reference substance, measured using HPLC methods, Tea Flower
The content that the content of total saposins is 3.6%, Chakasaponin II is 1.6%；
2) tea flower extract 2：After Tea Flower crushes, with 85 DEG C of the 50% ethanol refluxing extraction 3 times of 6 times of amounts, 1 is small every time
When, centrifugal filtration, merging filtrate, be concentrated under reduced pressure (12kpa, 45 DEG C) to density be 1.1g/ml, spray drying (140 DEG C of inlet air,
80 DEG C of outlet air, 70 DEG C of feed temperature), obtain tea flower extract 2.Using Chakasaponin II as reference substance, surveyed using HPLC methods
Fixed, the content that the content of tea tree flower total saponine is 8.6%, Chakasaponin II is 4.0%；
3) tea flower extract 3：After Tea Flower crushes, 3 times are extracted with 40 DEG C of the water of 10 times of amounts, every time 24 it is small when, centrifugation
Filtering, merging filtrate, film are concentrated into the 10% of original volume, 0.2 μm of membrane aperture, and the film in membrane separation uses molecular cut off
In the NF membrane of 100~1000Dal, tea tree flower total saponine can be retained, easy to separate water, concentrates tea flower extract solution,
Operating temperature in film concentration process is controlled below 40 DEG C, prevents tea tree flower total saponine to be destroyed because high fever is subject to, cold
It is lyophilized dry, obtain light brown tea flower extract 3 (see Fig. 3).Using Chakasaponin II as reference substance, measured using HPLC methods,
The content that the content of tea tree flower total saponine is 2.2%, Chakasaponin II is 1.2%；
4) tea flower extract 4：After Tea Flower crushes, 3 times are extracted with 80 DEG C of the water of 8 times of amounts, every time 3 it is small when, centrifuged
Filter, merging filtrate, film are concentrated into the 10% of original volume, 0.2 μm of membrane aperture, using molecular cut off receiving in 100~1000Dal
Filter membrane, controlling the operating temperature in film concentration process, trapped fluid is tea flower extract concentrate below 40 DEG C.Concentrate leads to
The D-101 macroporous resin columns anticipated are crossed, are first washed with deionized water de-, discard eluent, after with 50% ethanol elution, are received
Collect eluent, recycle ethanol, be dried under reduced pressure to obtain tea flower extract 4.Using Chakasaponin II as reference substance, using HPLC
Method measures, and the content that the content of tea tree flower total saponine is 52.0%, Chakasaponin II is 20.8%；
5) tea flower extract 5：After Tea Flower crushes, extracted 2 times with 70% alcohol reflux, for the first time plus 12 times are measured 70%
After 25 DEG C of soaked overnights of ethanol when small (12), 80 DEG C of refluxing extraction 1.5h；For the second time plus 10 times of 70% ethanol of amount, 80 DEG C of reflux carry
Take 1h.Centrifugal filtration, merging filtrate, be concentrated under reduced pressure (12kpa, 45 DEG C) to density be 1.1g/ml, concentrate is by anticipating
Good D-101 macroporous resin columns, are first washed with deionized water de-, except the impurity such as carbohydrate to molish reactions are negative, discard elution
Liquid, after with 50% ethanol elution, collects eluent, recycles ethanol, be dried under reduced pressure to constant weight, obtain tea flower extract 5.With
Chakasaponin II are reference substance, are measured using HPLC methods, and the content of tea tree flower total saponine is 80.0%,
The content of Chakasaponin II is 40.0%.
Embodiment 2：The preparation of line leaf goldspink flower extract
1) line leaf goldspink flower extract 1：After line leaf broom top crushes, extracted 3 times with 30 DEG C of the water of 15 times of amounts, 3 is small every time
When, centrifugal filtration, merging filtrate, be concentrated under reduced pressure (12kpa, 45 DEG C) to density be 1.1g/ml, spray drying (140 DEG C of inlet air,
80 DEG C of outlet air, 70 DEG C of feed temperature), obtain line leaf goldspink flower extract 1.Using rutin as reference substance, using ultraviolet spectrophotometry
Measure, the content of line leaf broom top general flavone is 6.5%；Using Aspalathin as reference substance, measured using HPLC methods,
The content of Aspalathin is 0.26%；
2) line leaf goldspink flower extract 2：After line leaf broom top crushes, with 60% ethanol, 85 DEG C of refluxing extractions 3 of 6 times of amounts
It is secondary, every time 3 it is small when, centrifugal filtration, merging filtrate, be concentrated under reduced pressure (12kpa, 45 DEG C) to density be 1.1g/ml, spray drying
(140 DEG C of inlet air, 80 DEG C of outlet air, 70 DEG C of feed temperature), obtains line leaf goldspink flower extract 2.Using rutin as reference substance, use is ultraviolet
Spectrophotometry, line leaf broom top general flavone are 10.8%；Using Aspalathin as reference substance, measured using HPLC methods,
The content of Aspalathin is 0.43%；
3) line leaf goldspink flower extract 3：After line leaf broom top crushes, 3 times are taken with 40 DEG C of the water extraction of 10 times of amounts, every time 24
Hour, centrifugal filtration, merging filtrate, film are concentrated into the 10% of original volume, 0.2 μm of membrane aperture, and the film in membrane separation uses
Molecular cut off can retain line leaf broom top general flavone, easy to separate water, enriching line leaf in the NF membrane of 100~1000Dal
Broom top extract solution, the operating temperature in film concentration process are controlled below 40 DEG C, prevent line leaf broom top general flavone because
To be subject to high fever to be destroyed, freeze-drying, obtains line leaf goldspink flower extract 3 (see Fig. 6).Using rutin as reference substance, using purple
Outer spectrophotometry, the content of line leaf broom top general flavone is 3.0%,；Using Aspalathin as reference substance, using HPLC
Method measures, and the content of Aspalathin is 0.12%；
4) line leaf goldspink flower extract 4：After line leaf broom top crushes, extracted 3 times with 80 DEG C of the water of 8 times of amounts, 3 is small every time
When, centrifugal filtration, merging filtrate, film be concentrated into original volume 10% (0.2 μm of membrane aperture, using molecular cut off 100~
The NF membrane of 1000Dal, controlling the operating temperature in film concentration process, trapped fluid is line leaf goldspink flower extract below 40 DEG C
Concentrate).Concentrate is first washed with deionized water de- by the AB-8 macroporous resin columns anticipated, discards eluent, after with
60% ethanol elution, collects eluent, recycles ethanol, is dried under reduced pressure to obtain line leaf goldspink flower extract 4.Using rutin as reference substance,
Using determined by ultraviolet spectrophotometry, the content of line leaf broom top general flavone is 54.6%；Using Aspalathin as reference substance, adopt
Measured with HPLC methods, the content of Aspalathin is 2.2%；
5) line leaf goldspink flower extract 5：After line leaf broom top crushes, extracted 2 times with 85% alcohol reflux, add 12 for the first time
After times amount 85% ethanol 25 DEG C of soaked overnights when small (12), 80 DEG C of refluxing extraction 1.5h；Second plus 8 times of 85% ethanol of amount, 80
DEG C refluxing extraction 1h.Merging extracting solution, centrifugal filtration, merging filtrate, filtrate decompression are concentrated into 0.2~0.8g (raw medicinal herbs)/ml,
Concentrate by the AB-8 macroporous resin columns anticipated, be first washed with deionized water it is de-, except the impurity such as carbohydrate are anti-to molish
It should be negative, discard eluent, after with 60% ethanol elution, collect eluent, recycle ethanol, be dried under reduced pressure to constant weight, obtain line
Leaf goldspink flower extract 5.Using rutin as reference substance, using determined by ultraviolet spectrophotometry, the content of line leaf broom top general flavone
For 80.0%；Using Aspalathin as reference substance, measured using HPLC methods, the content of Aspalathin is 3.8%.
Embodiment 3：The preparation of the present composition
Ambient humidity is controlled below 40%, 18-25 DEG C of temperature, tea flower extract and line leaf goldspink flower extract (table 1
In the tea flower extract n abbreviation tea n from embodiment 1；N) points of line leaf goldspink flower extract n abbreviation lines from embodiment 2
Not Fen Sui after cross 40-100 mesh sieves, claim sample according to composition compound proportion shown in table 1, intersect in batch mixer and add appropriate carrier
(such as resistant starch, maltodextrin, resistant dextrin, microcrystalline cellulose, hypromellose, superfine silica gel powder are medicinal to be received
Auxiliary material), tea flower extract, line leaf goldspink flower extract, appropriate carrier (such as resistant starch, maltodextrin, resistant dextrin,
The medicinal auxiliary material that can be received such as microcrystalline cellulose, hypromellose, superfine silica gel powder), incorporation time is 5~30min, rotating speed
For 20~30 revs/min, mixed powder crosses 20-40 mesh sieves, quantitative package.Moisture<5%, microbial limit meets regulation.
Extract and compound proportion contained by 1 present composition of table
The pulvis of 4 pharmaceutical composition of the present invention of embodiment, granule, tablet, hard capsule, oral liquid, the system of suspension
It is standby
Powder：Ambient humidity is controlled below 40%, 18-25 DEG C of temperature, and supplementary material crushes, sieves, weighs, in batch mixer
Intersect add the appropriate medicinal auxiliary material that can be received, the composition of embodiment 3, other compounding raw materials, it is appropriate it is medicinal can receive it is auxiliary
Material, incorporation time are 5~30min, and rotating speed is 20~30 revs/min, and mixed powder crosses 20-40 mesh sieves, quantitative package.Moisture<
5%, microbial limit meets regulation.
Granule：The composition of Example 3, other compounding raw materials, right amount of auxiliary materials.Mix, the wet granulation such as spraying, does
It is dry, sieving, whole grain, quantitative package.
Tablet：By obtained particle through further tabletting, dry, tablet.
Hard capsule：Obtained particle is loaded into capsule shells, that is, capsule is made.
Oral liquid：The composition of Example 3, other water-soluble compound raw materials, right amount of auxiliary materials, stirring and dissolving are fixed in water
Measure filling, sterilizing.
Suspension：The composition of Example 3, other compounding right amount of auxiliary materials such as raw material, emulsifying agent, stirring and dissolving in water,
High speed shear, high-pressure homogeneous, quantitative filling, sterilizing.
4 present composition of embodiment is to the expression of NPY/AGRP mRNA hormonal readinesses, rat body weight change and food ration
Influence
Investigate what the present composition expressed NPY/AGRP mRNA hormonal readinesses using high-fat-diet obese rats model
Influence.
If Normal group, high fat diet model group, according to embodiment 3 prepare 11 small dose group of composition (tea 4,
67.5mg/ (kgd)+line 4,67.5mg/ (kgd)), 11 middle dose group of composition (tea 4,135mg/ (kgd)+line 4,
135mg/ (kgd)), the heavy dose of group (tea 4,270mg/ (kgd)+line 4,270mg/ (kgd)) of composition 11, Tea Flower carry
Take thing group (tea 4,135mg/ (kgd)), line leaf goldspink flower extract group (line 4,135mg/ (kgd)) and according to embodiment 3
10 middle dose group of composition (tea 3,135mg/ (kgd)+line 3,432mg/ (kgd)) of preparation, wherein tea 4 are (using implementation
1 tea flower extract 4 of example), line 4 (using 2 line leaf goldspink flower extract 4 of embodiment), tea 3 (using 1 Tea Flower of embodiment extract
Thing 3), line 3 (use 2 line leaf goldspink flower extract 3 of embodiment.The dosage of composition is with tea flower extract and line leaf
To rat administration, the amount per kg represents goldspink flower extract daily；Above and below is when describing dosage, tea flower extract letter
Claim " tea ", line leaf goldspink flower extract is referred to as " line ".
Subjects are Sprague-Dawley rats, and daily timing gavage, records food ration, test preceding and off-test
Survey weight.
The results show that the expression for giving rat hypothalamus NPY and AGRP mRNA after high fat diet is increased, high fat diet is big
After mouse gives composition, the expression of hypothalamus NPY and AGRP mRNA reduces, in addition, composition substantially reduce food intake,
Suppress weight gain, hence it is evident that better than tea tree flower total saponine and line leaf broom top general flavone single drug.It follows that combination
Thing can obviously reduce the expression of hypothalamus NPY and AGRP mRNA, and suppression nervous centralis suppression hypothalamus appetite signals are related, by
This has the function that to reduce food-intake, loses weight, and feasible foundation is provided to find effective fat control measure.
1 materials and methods
1.1 material
Healthy male SD rat, 10d after ablactation, weight (100 ± 2g), animal and basal feed (heat 3500kcal/
Kg) provided by The Fourth Military Medical University's experimental animal center, the quality certification：SCXK (army) 2002-005).
High lipid food is voluntarily prepared, formula：Per 100g 12g containing yolk powder, lard 10g, Pig cholate 0.2g, casein 8g,
Milk powder 15g, salt 0.1g, dusty yeast 0.4g, basal feed 58g, heat 4346kcal/kg.
Trizol reagents, Reverse Transcriptase kit, PCR reaction kits are respectively by Invitrogen companies, precious bioengineering
Dalian Co., Ltd, precious bioengineering Dalian Co., Ltd provide.18s rRNAs, NPY and AGRP primers are by precious biological work
Cheng great Lian Co., Ltds synthesize.
1.2 method
SD rats 80, random packet, are divided into above-mentioned 8 groups by every group 10.Normal group gives basal feed, remaining
Each group gives high lipid food.Method for preparation of drug：With 0.9% physiological saline solution to required concentration.
Method of administration：Gavage.Capacity is administered：5ml/kg weight.
Administration time：2 times a day；During the morning 9, whens afternoon 5, is administered, successive administration 8 weeks.Normal group and high fat diet
The daily gavage of group gives 2 0.9% physiological saline, remaining each group according to dosage gastric infusion, and maintain this dosage to the 8th successively
Week.Every rat daily inleting appetite (g) is recorded, weight is surveyed with off-test before experiment.Experiment takes rat hypothalamus, in fact to 8 weekends
When fluorescence quantitative polymerase chain reaction method (RT-PCR) detection NPY and AGRP.
1.3RNA is extracted and real time fluorescent quantitative
Rats in test groups is at the 8th weekend, and taking-up hypothalamus is preserved in -80 DEG C of refrigerators after asepsis opens cranium.Trizol is decomposed
Inferior colliculus cerebral tissue, illustrates extraction RNA according to reagent, with the concentration and purity of nucleic acid-protein content meter measure total serum IgE.Calculate
The amount of total serum IgE needed for reverse transcription, adds corresponding reagent according to Reverse Transcriptase kit specification, carries out reverse transcription, reaction condition：
37 DEG C of 15min, 85 DEG C of 5s, total serum IgE are transcribed into cDNA.The content of NPY, AGRP and 18s rRNA uses RG-3000RT-
PCR instrument is measured.Fluorescence used in real time fluorescent quantitative is SYBR Premix Ex TaqTM, and reaction solution volume is 20 μ l, according to
Secondary is 10 μ l of SYBR Premix Ex Taq, 7.6 μ l of each 0.4 μ l of two kinds of primers, 1.6 μ l of template and deionized water.NPY、AGRP
It is as follows with the primer sequence of 18s rRNAs：NPY：P1 is TGTGAAACCAGTCTGCCTGT, P2：
CAACGACAACAAGGGAAATG；AGRP：P1 is ACGGTGGGCCCTTTATTAG, P2：GGACACAGCTCAGCAACATT；18s
RRNA：P1 is TTCGGAACTGAGGCCATGAT, P2：CGAACCTCCGACTTTCGTTC, is carried out, PCR using two-step method
Pre-degeneration 95 DEG C of 10s, PCR reaction：95 DEG C of 5s, 60 DEG C of 30s, repeat 40 circulations (NPY) or 45 circulations (AGRP).As a result divide
Analysis uses 2-△△CTMethod, 18s rRNAs are house-keeping genes, and house-keeping gene subtracts target gene (NPY or AGRP) and draws △
CT, then selects a CT value from control group and △ CT is calibrated, and each △ CT subtract calibration CT and draw △ △ CT values, calculate
Go out 2-△△CT, this numerical value is the content of the target gene of relative quantification.
1.4 statistical method
Test data uses difference between one-way ANOVA variance analysis population means first, then multiple ratio between mean
Examined compared with using Post-Hoc-Tests LSD.All statistical procedures carry out statistical procedures using SPSS statistical softwares.
2 results
The influence that 2.1 compositions express high-fat-diet obese rats hypothalamus NPY and AGRP mRNA
As shown in table 2, compared with Normal group, rat hypothalamus NPY and AGRP mRNA are expressed after giving high fat diet
Increase.Compared with high fat diet model group, after giving high, medium and low dosage composition 11, NPY and AGRP mRNA expression is different
Degree significantly reduces；After 4 single administration of tea flower extract, NPY and AGRP mRNA expression significantly reduce, fall with it is low
Dosage composition 11 is suitable, but not as good as middle dosage and 11 administration group of high dose composition；4 groups of line leaf goldspink flower extract is shown
Downward trend, but there is no significant difference.Visible composition is substantially better than tea flower extract or line leaf goldspink flower extract group
Single administration, tea flower extract are combined to high-fat-diet obese rats hypothalamus NPY and AGRP with line leaf goldspink flower extract
MRNA expression shows notable coordinate repression.
The influence of hypothalamus NPY and AGRP mRNA expression after 2 composition 11 of table tests high-fat-diet obese rats 8 weeks
(* p ＜ 0.01vs Normal groups；#p ＜ 0.05vs high fat diet model groups；##p ＜ 0.01vs high fat
Diet model group)
As shown in table 3, compared with high fat diet model group, after giving 10 middle dosage of composition, NPY and AGRP mRNA tables
Up to significantly reducing, but decline degree and be substantially less than 11 middle dose group of composition, i.e., active ingredient is total including Tea Flower in extract
The composition 11 that saponin(e and line leaf broom top general flavone greatly improve is compared to composition 10, to hypothalamus NPY and AGRP mRNA
It is stronger to express downward effect, there is significant difference.In addition, 10 middle dose group drug effect of composition is with being used alone Tea Flower extraction
Quite, but the content of Tea Flower saponin(e is substantially less than the saponin content of tea flower extract 4 to thing 4 (being shown in Table 2) contained by composition 10,
Line leaf goldspink flower extract 3 associated with prompting has significantly played synergistic effect.
Hypothalamus NPY and the shadow of AGRP mRNA expression after 3 different components of table test high-fat-diet obese rats 8 weeks
Ring
(* p ＜ 0.05vs high fat diet model groups, * * p ＜ 0.01vs high fat diet model groups；0.05 group of #p ＜
Compound 10vs compositions 11)
Influence of 2.2 compositions to high-fat-diet obese rats changes of weight
As shown in table 4, compared with Normal group, the rat body weight of model group and each administration group is equal after giving high fat diet
Dramatically increase, the weight of model group more normally organizes rat continuous increase after high fat diet after 8 weeks.With high fat diet model group ratio
Compared with the weight of high, medium and low 11 groups of rats of dosage composition significantly reduces in various degree after being administered 8 weeks；Tea flower extract 4
After single administration, rat body weight significantly reduces, but fall is not as good as 3 dosage groups of composition 11；Line leaf broom top is extracted
4 groups of thing shows downward trend, but does not have significant difference.Visible composition is substantially better than tea flower extract or line leaf goldspink
The single administration of flower extract, tea flower extract is combined with line leaf goldspink flower extract drops the weight of high-fat-diet obese rats
It is low to show notable coordinate repression.
The influence of changes of weight before and after 4 composition 11 of table tests high-fat-diet obese rats 8 weeks
(* * p ＜ 0.001vs Normal groups；#p ＜ 0.05vs high fat diet model groups；##p ＜ 0.01vs high
Fat diet model group；###p ＜ 0.001vs high fat diets model group)
As shown in table 5, compared with high fat diet model group, 10 middle dosage of composition is given after 8 weeks, rat body weight significantly drops
It is low, but decline degree and be substantially less than 11 middle dose group of composition, i.e., active ingredient includes tea tree flower total saponine and line in extract
For the composition 11 that leaf broom top general flavone greatly improves compared to composition 10, the effect mitigated to rat body weight is stronger, declines
Amplitude bigger, has significant difference.In addition, 10 middle dose group drug effect of composition (is shown in Table with tea flower extract 4 is used alone
4) quite, but the content of Tea Flower saponin(e contained by composition 10 is substantially less than the content of saponin(e in tea flower extract 4, prompts connection
Line leaf goldspink flower extract 3 has significantly played synergistic effect.
The influence of changes of weight before and after 5 different components of table test high-fat-diet obese rats 8 weeks
(* p ＜ 0.05vs high fat diet model groups, * * p ＜ 0.01vs high fat diet model groups, * * * p ＜
0.001vs high fat diet model groups；0.05 composition 10vs compositions 11 of #p ＜)
Influence of 2.3 compositions to high-fat-diet obese rats total foodstuff intake
As shown in table 6, compared with Normal group, the total foodstuff intake of model group rats after high fat diet 8 weeks is given
Dramatically increase.Compared with high fat diet model group, the total foodstuff of rat absorbs after high, medium and low dosage composition 11 after being administered 8 weeks
Amount significantly reduces in various degree；After the single administration of tea flower extract 48 weeks, the total foodstuff intake of rat writes and reduces, and declines
Amplitude is suitable with low dose group compound 11, but not as good as middle dosage and 11 administration group of high dose composition；Line leaf goldspink flower extract 4
Group shows downward trend, but does not have significant difference.Visible composition is substantially better than tea flower extract or line leaf broom top
The single administration of extract, tea flower extract are combined with line leaf goldspink flower extract and high-fat-diet obese rats total foodstuff are absorbed
The reduction of amount shows notable coordinate repression.
The influence of total foodstuff intake after 6 composition 11 of table tests high-fat-diet obese rats 8 weeks
(* p ＜ 0.01vs Normal groups；#p ＜ 0.05vs high fat diet model groups；###p ＜ 0.001vs high
Fat diet model group)
As shown in table 7, compared with high fat diet model group, 10 middle dosage of composition is given after 8 weeks, the intake of rat total foodstuff
Amount substantially reduces, but reduces degree and be substantially less than 11 middle dose group of composition, i.e., it is total to include Tea Flower for active ingredient in extract
The composition 11 that saponin(e and line leaf broom top general flavone greatly improve is compared to composition 10, the reduction effect to rat food ration
It is stronger, there is significant difference.In addition, 10 middle dose group drug effect of composition is with being used alone tea flower extract 4 (being shown in Table 6) phase
When, but the content of Tea Flower saponin(e contained by composition 10 is substantially less than the saponin content of tea flower extract 4, line associated with prompting
Leaf goldspink flower extract 3 has significantly played synergistic effect.
The influence of total foodstuff intake after 7 different components of table test high-fat-diet obese rats 8 weeks
(* p ＜ 0.05vs high fat diet model groups, * * p ＜ 0.01vs high fat diet model groups, * * * p ＜
0.01vs high fat diet model groups；0.05 composition 10vs compositions 11 of #p ＜)
Rat body weight dramatically increases after high fat diet is given in this experiment, and energy intake dramatically increases, the molten slurry group of hypothalamus
Knit middle NPY and AGRP mRNA and significantly express increase, illustrate the increase of high-fat-diet obese rats weight and food ration and NPY and
The height expression of AGRP mRNA is related.High-fat-diet obese rats give weight, the reduction of total food ration after composition in this experiment,
NPY and AGRP mRNA expression reduces, thus it is speculated that composition may be by reducing the expression of hypothalamus NPY and AGRP mRNA, and sends out
Wave the effect for total food ration that loses weight, reduces, hence it is evident that better than tea flower extract and line leaf goldspink flower extract single drug,
After prompting tea flower extract and line leaf goldspink flower extract are used in combination, collaboration are played and has suppressed NPY and AGRP mRNA expression
Effect.In addition, result of the test shows, general flavone contained by total saposins contained by tea flower extract and line leaf goldspink flower extract
After content improves, the effect of complex composition, is more excellent.
5 human feeding trial of embodiment
Tea Flower (is implemented with the new raw-food material that line leaf broom top is Ministry of Public Health's approval, experiment with tea flower extract
One tea tree flower total saponine 3 of example) with line leaf broom top general flavone (embodiment two wires leaf goldspink flower extract 3) be water extraction, peace
Full property is preferable.On the basis of above-mentioned animal experiment, choose middle dose group compound 10 dosage (tea 3,135mg/ (kgd)+line 3,
432mg/ (kgd)), calculated with its 1/10 dosage as people's dosage (tea 3,150mg/ (70kgd)+line 3,480mg/
(70kg·d)).Calculated by respectively being taken before three meals in a day 1 time, be tea 3 each taking dosage, 50mg/ times+line 3,160mg/ times.
By BMI values 25-35 (24≤BMI≤27, it is overweight；27≤BMI≤30, Mild Obesity；30≤BMI≤35, moderate fertilizer
It is fat), the adult at age 20-58 Sui is as research object, and men and women is fifty-fifty, and physical examination result is in good health before all subject's experiments
(blood glucose is normal), voluntary participation experiment.30 experiment group objects are allowed in 2 months in the case of normal diet, it is daily early, in,
Evening three takes 50mg tea flower extracts 3,160mg line leaf goldspinks flower extract 3 and both compositions for 15 minutes before the meal respectively
(composition 10), every group of 10 people, periodic measurement test weight, waistline, BMI values and the body fat rate of group objects, off-test test
Blood glucose value.After human body examination clothes experiment 15 days, after subject participates in quantitative criterion lunch, measure food intake rate and assess postprandial
3h, 5h, 8h produce the number and ratio of hunger, and it is Normal group separately to take 10 people.
1. influence of the composition 10 to the postprandial total foodstuff uptake ratio of adult's quantitative criterion and hunger
As shown in table 8, normally organizing postprandial 3h has 80% generation hunger.Compared with Normal group, take within 15 minutes before the meal
Significantly significantly reduced with 10 groups of total foodstuff intake of composition, the ratio that 5h, 8h produce hunger accounts for 10%, 40% respectively；
Individually taking the total foodstuff intake of tea flower extract group (tea 3) significantly reduces, but reduces amplitude and be substantially less than composition 10
Group (p ＜ 0.001), the ratio that 5h, 8h produce hunger account for 30%, 70% respectively；Individually take line leaf goldspink flower extract group
The total foodstuff intake of (line 3) is declined slightly trend, but no difference of science of statistics compared with normal group, and 5h, 8h produce hunger
Ratio accounts for 80%, 100% respectively.Visible composition be substantially better than tea flower extract or line leaf goldspink flower extract it is single to
Medicine, tea flower extract is combined to reducing intake with line leaf goldspink flower extract, delay hunger shows significantly to cooperate with suppression
Make and use.
The postprandial total foodstuff uptake ratio of 8 present composition of table, 10 quantitative criterion and postprandial hunger generation time test result
(* p ＜ 0.05vs Normal groups；* * p ＜ 0.001vs Normal groups；###p ＜ 0.001vs are combined
Thing group)
2. composition 10 is to adult's weight and the influence of body fat rate change
As shown in table 9, take within 15 minutes before the meal composition 10 group after 8 weeks weight, BMI values, waistline, body fat rate it is significantly notable
Reduce；The independent weight for taking tea flower extract group (tea 3), BMI values, waistline, body fat rate decline, but it is notable to reduce amplitude
Less than composition group (p ＜ 0.001)；Individually take weight, BMI values, waistline, the body fat of line leaf goldspink flower extract group (line 3)
Rate is declined slightly trend, but changes unobvious.Above each group does not influence blood glucose value.Visible composition is substantially better than Tea Flower
Extract or the single administration of line leaf goldspink flower extract, tea flower extract are combined to weight, BMI with line leaf goldspink flower extract
The reduction of value, waistline, body fat rate shows notable coordinate repression, and security is good.
9 present composition 10 of table tries the influence to be grown up BMI, weight, waistline, body fat rate, blood glucose after taking 8 weeks
(* * p ＜ 0.001vs compositions group)
Above human experiment is the results show that take the tested of tea flower extract and line leaf broom top extractive composition
Person, its weight, BMI values, waistline and body fat rate are remarkably decreased, and blood glucose value change without exception, it is seen that tea flower extract with
There is the combination of line leaf goldspink flower extract significantly synergistic effect, its body weight control to significantly reduce, produce with subject's food intake
The time obvious postpone of raw hunger is significantly correlated.
The effect of above-described embodiment indicates that the essentiality content of the present invention, but the protection of the present invention is not limited with this
Scope.It will be understood by those of ordinary skill in the art that can to technical scheme technical scheme is modified or replaced equivalently,
Without departing from the essence and protection domain of technical solution of the present invention.
Claims (9)
1. a kind of composition for body weight control, it is characterised in that the composition is with tea flower extract and line leaf gold
For sparrow flower extract made of raw material, wherein tea flower extract and the part by weight of line leaf goldspink flower extract is 1-20:20-
1。
2. composition according to claim 1, it is characterised in that total saponin content is not less than in the tea flower extract
2.0%, contained Chakasaponin II are not less than 1.0%；Line leaf broom top extractive total flavone content is not less than 2.0%, institute
It is not less than 0.1% containing Aspalathin.
3. composition according to claim 2, its preparation method are as follows：
1) after Tea Flower crushes, extracted 1-3 times with the ethanol of the 6-15 times of water measured or various concentrations, 25-100 DEG C of temperature, every time
When 0.5-24 is small, filtering, merging filtrate, is concentrated under reduced pressure or film concentrates, and spray drying or freeze-drying, obtain tea flower extract；
2) after line leaf broom top crushes, extracted 1-3 times with the ethanol of the 6-15 times of water measured or various concentrations, 25-100 DEG C of temperature,
When 0.5-24 is small every time, filtering, merging filtrate, is concentrated under reduced pressure or film concentrates, spray drying or freeze-drying, dry that line leaf is golden
Sparrow flower extract；
3) it is 1-20 according to part by weight by tea flower extract and line leaf goldspink flower extract:20-1 after mixing, is added
Appropriate pharmaceutically acceptable auxiliary material is uniformly mixed, to obtain the final product.
4. composition according to claim 1, it is characterised in that the tea flower extract and line leaf goldspink flower extract
Part by weight be preferably 1-5:5-1.
5. composition according to claim 4, it is characterised in that the tea flower extract total saponin content is not less than
50%, contained Chakasaponin II are not less than 20%；Line leaf broom top extractive total flavone content is contained not less than 50%
Aspalathin is not less than 2%.
6. composition according to claim 5, its preparation method are preferably as follows：
1) after Tea Flower crushes, the ethanol that water or various concentrations are measured with 8-12 times extracts 1-3 times, 25-100 DEG C of temperature, every time
When 0.5-24 is small, filtering, merging filtrate, is concentrated under reduced pressure or film concentration, concentrate pass through the D101 macroporous absorptions anticipated
Resin column, is first washed with deionized water de-, discards eluent, after with 50-90% ethanol elutions, collects eluent, recycles ethanol, subtract
Press dry dry tea flower extract；
2) after line leaf broom top crushes, extracted 1-3 times with the ethanol of the 8-12 times of water measured or various concentrations, 25-100 DEG C of temperature,
When each 0.5-24 is small, filtering, merging filtrate is concentrated under reduced pressure or film concentration, and concentrate passes through the AB-8 macropores anticipated
Adsorption resin column, is first washed with deionized water de-, discards eluent, after with 50-90% ethanol elutions, collects eluent, recycles second
Alcohol, is dried under reduced pressure to obtain line leaf goldspink flower extract；
3) it is 1-5 according to part by weight by tea flower extract and line leaf goldspink flower extract:5-1 after mixing, is added suitable
Measure pharmaceutically acceptable auxiliary material to be uniformly mixed, to obtain the final product.
7. according to the composition described in claim 1-6, it is characterised in that the composition can cooperate with suppression neuropeptide tyrosine/thorn
Mouse peptide gene GAP-associated protein GAP (AGRP) mRNA hormonal readinesses are secreted, and are reached and are reduced food intake, delay hunger, control body weight
Effect.
8. the oral drugs for the body weight control being prepared with the composition according to claim 1-6, health food, special doctor
Purposes formula food or function nutrition food are learned, for the prevention and treatment of metabolic disorder disease caused by fat or obesity,
It is characterized in that the composition described in by claim 1-7, mixes with pharmaceutic adjuvant, oral formulations are made, it can be powder,
Any one in granule, tablet, hard capsule, oral liquid, suspension.
9. the oral drugs for the body weight control being prepared with composition according to claim 7, health food,
Special medicine purposes formula food or function nutrition food, for the pre- of metabolic disorder disease caused by fat or obesity
Anti- and treatment, it is characterised in that by the composition described in claim 1-7, mixed with pharmaceutic adjuvant, oral formulations are made, it can
To be any one in powder, granule, tablet, hard capsule, oral liquid, suspension.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109932448A (en) * | 2019-03-29 | 2019-06-25 | 完美（广东）日用品有限公司 | The content assaying method of effective component in a kind of line leaf broom top and its product |
| CN109959735A (en) * | 2019-03-29 | 2019-07-02 | 完美（广东）日用品有限公司 | The content assaying method of three kinds of ingredients in line leaf broom top, line leaf goldspink flower extract and line leaf goldspink jasmine tea |
| CN113975335A (en) * | 2021-12-29 | 2022-01-28 | 仙乐健康科技股份有限公司 | Composition for controlling appetite and inducing satiety |
| CN114847380A (en) * | 2022-05-09 | 2022-08-05 | 杭州终维食品科技有限公司 | Caffeine-free tea composition with skin color brightening effect and preparation method and application thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109932448A (en) * | 2019-03-29 | 2019-06-25 | 完美（广东）日用品有限公司 | The content assaying method of effective component in a kind of line leaf broom top and its product |
| CN109959735A (en) * | 2019-03-29 | 2019-07-02 | 完美（广东）日用品有限公司 | The content assaying method of three kinds of ingredients in line leaf broom top, line leaf goldspink flower extract and line leaf goldspink jasmine tea |
| CN113975335A (en) * | 2021-12-29 | 2022-01-28 | 仙乐健康科技股份有限公司 | Composition for controlling appetite and inducing satiety |
| CN114847380A (en) * | 2022-05-09 | 2022-08-05 | 杭州终维食品科技有限公司 | Caffeine-free tea composition with skin color brightening effect and preparation method and application thereof |
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| CN107998220B (en) | 2020-09-18 |
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