CN110025579A - It is micronized tetrahydro curcumin and its preparation method and application - Google Patents
It is micronized tetrahydro curcumin and its preparation method and application Download PDFInfo
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Abstract
The present invention provides a kind of micronization tetrahydro curcumin, the particle size range of the micronization tetrahydro curcumin is 1~100 μm.The present invention also provides the preparation methods and purposes of above-mentioned micronization tetrahydro curcumin.Micronization tetrahydro curcumin of the invention, drug particle size is small, is conducive to discharge and absorb.With tetrahydro curcumin, micronization tetrahydro curcumin of the invention has the effect of better hypoglycemic and reducing blood lipid, simultaneously; it can be improved GLP-1 protein expression; promote insulin secretion, have better protective effect to insulin B, has better effect for treatment diabetes B.
Description
Technical field
Present invention relates particularly to micronization tetrahydro curcumins and its preparation method and application.
Background technique
Diabetes are one group of metabolic diseases characterized by hyperglycemia.Hyperglycemia be then due to defect of insulin secretion or
Its biological effect is impaired, or both have concurrently and cause.Long-standing hyperglycemia when diabetes, cause various tissues, especially eye,
Kidney, heart, blood vessel, the chronic lesion of nerve, dysfunction.Two kinds can be divided into regard to current diabetes, be 1 type and 2 types respectively
Diabetes.Type 1 diabetes are can not independently to generate enough insulin due to gene defect, and cell can not be allowed by lacking insulin
Extra blood glucose is stored, for human body to Hyperglycemia occur, typical " three-many-one-little " occurs in when severe hyperglycemia
Symptom (more drinks, diuresis, more foods and syntexis), " three-many-one-little " symptom becomes apparent when ketosis or ketoacidosis occurs.2 types sugar
Urinating disease is due to there is Insulin Resistance the day after tomorrow, and insulin secretion is normal, but insulin receptor can not work normally, cell
Insulin can not be responded and carry out the storage of extra blood glucose, human body to Hyperglycemia occur, be mainly shown as fatigue and weak,
It is fat, thirsty and big blood vessel and microvascular complication can often occur before clarifying a diagnosis.Diabetes B is common in person in middle and old age
People, overweight people's disease incidence is high, often can be with hypertension, the diseases such as dyslipidemia, artery sclerosis.
Tetrahydro curcumin is a kind of natural function whitening raw materials.Patent 201010100518.4 discloses tetrahydro turmeric
Purposes of the element in the drug of preparation prevention or/and treatment diabetes, but since tetrahydro curcumin granularity used is larger, treatment
Diabetes effect is not obvious enough.
Summary of the invention
To solve the above problems, the present invention provides a kind of micronization tetrahydro curcumins and its preparation method and application.
The present invention provides a kind of micronization tetrahydro curcumin, it is described micronization tetrahydro curcumin particle size range be 1~
100μm。
Further, the particle size range of the micronization tetrahydro curcumin is 1~50 μm.
The present invention also provides the preparation methods of micronization tetrahydro curcumin above-mentioned, it includes the following steps:
The medicinal vibration type ultramicro disintegrator of tetrahydro curcumin raw material is crushed into 5~60min, obtains tetrahydro curcumin micro mist.
Further, it includes the following steps:
The medicinal vibration type ultramicro disintegrator of tetrahydro curcumin raw material is crushed into 15min, controls 25 DEG C of temperature hereinafter, obtaining
Tetrahydro curcumin micro mist.
The present invention also provides micronization tetrahydro curcumins above-mentioned to prepare the purposes in hypoglycemic drug.
The present invention also provides purposes of the micronization tetrahydro curcumin above-mentioned in the drug of preparation reducing blood lipid.
The present invention also provides purposes of the micronization tetrahydro curcumin above-mentioned in the drug of preparation treatment diabetes.
Further, the diabetes are spontaneous diabetes B.
Micronization tetrahydro curcumin of the invention, drug particle size is small, is conducive to discharge and absorb.With tetrahydro curcumin, sheet
The micronization tetrahydro curcumin of invention has the effect of better hypoglycemic and reducing blood lipid, meanwhile, it is capable to improve GLP-1 albumen table
It reaches, promotes insulin secretion, have better protective effect to insulin B, have better effect for treatment diabetes B.
Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific embodiment of form by the following examples remakes further specifically above content of the invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on above content of the present invention
The technology realized all belongs to the scope of the present invention.
Detailed description of the invention
Fig. 1 is the testing graininess result of present invention micronization tetrahydro curcumin.
Fig. 2 is the particle size distribution figure of present invention micronization tetrahydro curcumin.
Fig. 3 is present invention micronization tetrahydro curcumin to insulin in spontaneous diabetes B db/db mice pancreatic tissue
The immunohistochemistry figure of influence；A: normal group；B: model group；C tetrahydro curcumin group；D is micronized tetrahydro curcumin 100mg/kg group.
Fig. 4 is present invention micronization tetrahydro curcumin to GLP-1 in spontaneous diabetes B db/db mice pancreatic tissue
The immunohistochemistry figure of influence；A: normal group；B: model group；C tetrahydro curcumin group；D is micronized tetrahydro curcumin 100mg/kg group.
Specific embodiment
The preparation of 1 present invention micronization tetrahydro curcumin of embodiment
Will tetrahydro curcumin bulk pharmaceutical chemicals coarse powder put into micronizer in, control 25 DEG C of temperature hereinafter, crush 15min,
Take out to get.
The particle size determination of 2 present invention micronization tetrahydro curcumin of embodiment
The smashed micro mist of embodiment 1 is measured with the dual-purpose laser particle analyzer of JL-6000 type wet-dry change.Testing graininess
As a result as shown in Figure 1, particle size distribution figure is as shown in Figure 2.
Particle size determination result illustrates: the particle size range that the present invention is micronized tetrahydro curcumin is 1~100 μm, main grain
Diameter range is 1~50 μm, and average grain diameter is 14.29 μm.
Beneficial effects of the present invention are proved below by way of the mode of experimental example:
Experimental example 1 is micronized influence of the tetrahydro curcumin to spontaneous diabetes B db/db mouse
1, experimental material
1) experimental drug:
It is micronized tetrahydro curcumin, 14.29 μm of average grain diameter, purity 95% is prepared by embodiment 1；
Tetrahydro curcumin, 100~500 μm of partial size, purchase.
2) experimental animal:
SPF grades of db/db mouse (SPF grades of diabetes B mouse), strain BKS.Cg-Dock7m+/+Leprdb/ Nju, gene
Type (Lepdb) mut/mut, ♂, 30,6 week old；Wild type control group mouse, ♂, 10,6 week old, strain BKS.Cg-Dock7m+/+Leprdb/ Nju, genotype (Lepdb)wt/wt.It is provided by Nanjing University-Nanjing biological medicine research institute animal center.
3) experiment reagent:
Insulin (Iinsulin) kit (lot number: 21H031, manufacturer: Yi Kesai Biotechnology Co., Ltd)；
Total cholesterol (TC) assay kit (CHOD-PAP method) (lot number: 0717031, manufacturer: the limited public affairs of mikey biology share
Department)；Triglycerides (TG) assay kit (GPO-PAP method) (lot number: 0716061, manufacturer: mikey biology share is limited
Company)；High-density lipoprotein cholesterol (HDL-C) assay kit (CAT method) (lot number: 0516091, manufacturer: Michelson
Object limited liability company)；Low density lipoprotein cholesterol (LDL-C) assay kit (CAT method) (lot number: 0616101, production
Producer: mikey Biological Co., Ltd.)；Insulin (Insulin) (article No.: ab63820, manufacturer: abcam)；Pancreas is high
Blood glucose element sample peptide 1 (GLP-1) (article No.: 13329, manufacturer: abcam)；Secondary antibody: instant Rapid Immuno group kit
(article No.: KIT-5004, manufacturer: Foochow steps new)；Paraformaldehyde (lot number: 2015080701, manufacturer: Chengdu section
Longhua work chemical reagent work)；Sodium carboxymethylcellulose (CMC-Na), Chengdu Ke Long chemical reagent factory.
4) laboratory apparatus:
(model: 7020 type of Hitachi, manufacturer: Hitachi, Amada Co., Ltd. new and high technology is public for automatic clinical chemistry analyzer
Department)；Electronic balance (d=0.1mg) (model: ME204/02, manufacturer: Mei Tele-support benefit instrument (Shanghai) limited public affairs
Department)；DM3000 type is just setting microscope Pathologic image analysis instrument (German Lycra company)；HMIAS-2000 high-definition color medicine
Picture and text analysis system；The multi-functional all-wave length number scanner of RIOSKAN FLASH type (Thermo Scientific company)；
DHG-9070A type electric heating constant-temperature blowing drying box (the upper macro experimental facilities Co., Ltd of Nereid)；Blood-sugar detecting instrument and blood sugar test paper
(glucose dehydrogenase method) (lot number: 460537, manufacturer: product (Shanghai) Co., Ltd., Roche Diagnistics)；TSJ-Q type is complete certainly
Move closed tissue dewatering agent (Changzhou Zhong Wei Electronic Instruments Plant)；Cycle type slicer (German LEICA)；BMJ-III type paraffin
Embedding machine (Changzhou Zhong Wei Electronic Instruments Plant)；CX31 optical microscopy (Japanese OLYMPUS)；A set of (the ophthalmology of disinfection of surgical equipment
Tweezers, scissors, scalpel).
2, experimental method
SPF grades of db/db mouse, ♂, 30,6 week old；Wild type control group mouse, ♂, 10,6 week old.SPF grades of mouse are suitable
Answering property is raised after two weeks, is deprived of food but not water 6 hours, and mouse cuts tail and takes blood, measures mouse blood sugar with Roche blood glucose meter and test strips
Value, weighs mouse weight.SPF grades of db/db mouse are randomly divided into 3 groups, every group 10, each group is respectively:
1. model group: daily set time stomach-filling 0.5%CMC-Na (sodium carboxymethylcellulose) solution, stomach-filling volume
0.1ml/10g；
2. tetrahydro curcumin group (100mg/kg): daily set time stomach-filling tetrahydro curcumin, given low are that every kg is small
Mouse stomach-filling 100mg tetrahydro curcumin；
3. being micronized tetrahydro curcumin group (100mg/kg): daily set time stomach-filling is micronized tetrahydro curcumin, stomach-filling
Dosage is that every kg intragastric administration on mice 100mg is micronized tetrahydro curcumin；
It wherein, is 2. and 3. treatment group.
Wild type control group mouse is used as 4. normal group, daily set time stomach-filling 0.5%CMC-Na solution.
After the completion of grouping, tetrahydro curcumin and micronization tetrahydro curcumin are prepared respectively with 0.5%CMC-Na solution, is obtained
Tetrahydro curcumin solution and micronization tetrahydro curcumin solution concentration be 10mg/mL.
During animal is administered, same time gastric infusion is fixed daily, tetrahydro curcumin group dosage 100mg/kg is micro-
Dusting tetrahydro curcumin group dosage is 100mg/kg, normal group and model group stomach-filling 0.5%CMC-Na solution, stomach-filling volume
It is 0.1ml/10g, successive administration 6 weeks.Each group mouse surveys a weight and food ration in the fixation same time respectively weekly, and
It is deprived of food but not water 6 hours measurement fasting blood sugars.
During animal is administered, model group and tetrahydro curcumin group have 3 dead mouses respectively, are micronized tetrahydro curcumin group
There are 4 dead mouses.
After administration is fully completed, mouse empty stomach 12h plucks eyeball and takes blood.4 DEG C of centrifugations 3000r/min, 10min separate serum
In centrifuge tube, -20 DEG C of refrigerator saves to be measured.
After the completion of mouse blood sampling, cervical dislocation puts to death mouse, and mouse web portion is sterilized with cotton ball soaked in alcohol, Isolation of pancreatic, liver
Tissue, the paraformaldehyde solution that pancreatic tissue is put into rapidly to 4% are fixed.Liver organization is cleaned with physiological saline, is weighed, ice
Upper separation liver, the paraformaldehyde solution that partial liver is put in 4% are fixed, for HE dyeing and immunohistochemistry measurement, part liver
It is dirty freeze liquid nitrogen be transferred to -80 degree refrigerators save it is to be measured.
Observation index:
2. observing mouse ordinary circumstance；
2. blood biochemical detects: full-automatic biochemical analyzer detects the indexs of correlation such as blood glucose, blood lipid, and ELISA method measures pancreas
Island element (Iinsulin) content.
3. liver organ index；
4. pathologic finding: insulin, GLP-1 (glucagon-like-peptide-1) immunohistochemical staining in hepaticopancreatic tissue.
3, experimental result
1) mouse ordinary circumstance
During experiment, wild type control group mouse (normal group) fur is smooth glossy, and freely, the state of mind is good for activity,
Diet is normal；SPF grades of db/db mouse of model group become intensely dark pool with the process fur of experiment, do not like activity, have more
The phenomenon that food, diuresis, generates, and figure is partially fat, and the state of mind is poor；Treatment group mouse has compared to model group mouse everyway
Improved.
2) blood sugar detection result
Blood sugar detection the results are shown in Table 1.
Table 1 is micronized influence of the tetrahydro curcumin to spontaneous diabetes B db/db mouse blood sugar
Note: compared with model control group, P < 0.05**P < 0.01 *；The #P < 0.05##P < compared with tetrahydro curcumin group
0.01
As shown in Table 1, tetrahydro curcumin group and micronization tetrahydro curcumin group are able to suppress blood glucose compared with model group
Growth, wherein micronization tetrahydro curcumin group inhibit blood glucose increase effect be better than tetrahydro curcumin group.Test result is said
Bright: under identical dosage, the present invention is micronized the hypoglycemic effect of tetrahydro curcumin and is substantially better than tetrahydro curcumin.
3) blood biochemical detects
Blood biochemical Testing index is shown in Table 2.Wherein it is highly dense to refer to that total cholesterol, TG refer to that triglycerides, HDL-C refer to by TC
Degree lipoprotein cholesterol, LDL-C refer to low density lipoprotein cholesterol.
Table 2 is micronized influence of the tetrahydro curcumin to spontaneous diabetes B db/db mouse blood biochemical indicator
Note: compared with model control group, P < 0.01 * P < 0.05, * *；#P < 0.05, ##P < compared with tetrahydro curcumin group
0.01。
As shown in Table 2, tetrahydro curcumin group and TC, TG, HDL-C and LDL-C in micronization tetrahydro curcumin group blood
Concentration is below model group, wherein the concentration of TC, TG, HDL-C and LDL-C are lower in blood in micronization tetrahydro curcumin group
In tetrahydro curcumin group.And TC, TG, HDL-C and LDL-C are indexs relevant to blood lipid, TC, TG, HDL-C and LDL-C concentration
It is higher, illustrate blood lipid level height.Test result explanation: under identical dosage, the present invention is micronized tetrahydro curcumin drop
The effect of low blood lipid is substantially better than tetrahydro curcumin.
4) liver organ index
Liver organ index is the ratio of liver and weight, and liver organ index measurement result is shown in Table 3.
Table 3 is micronized influence of the tetrahydro curcumin to spontaneous diabetes B db/db mice organs index
| Group | N (only) | Dosage (mg/kg) | Liver organ index (mg/100g) |
| Normal group | 10 | —— | 429.64±22.82** |
| Model group | 7 | —— | 489.80±45.23 |
| Tetrahydro curcumin group | 7 | 100 | 466.67±35.24 |
| It is micronized tetrahydro curcumin group | 6 | 100 | 421.35±31.84**# |
Note: the 0.05 * * P < 0.01 of * P < compared with model group；The 0.05 ##P < of #P < compared with tetrahydro curcumin group
0.01
As shown in Table 3, model group liver organ index is higher than normally organizing, and illustrates that congested, water occurs in model group mouse liver
The lesions phenomenons such as swollen or hypertrophy.The liver organ index of tetrahydro curcumin group and micronization tetrahydro curcumin group is below mould
Type group illustrates after tetrahydro curcumin is administered and is micronized tetrahydro curcumin that hepatic disease phenomenon is alleviated, wherein being micronized four
The organ index of hydrogen curcumin group is more below tetrahydro curcumin group.Test result explanation: under identical dosage, the present invention
Micronization tetrahydro curcumin is more advantageous to the alleviation of hepatic disease phenomenon.
5) insulin content measures
The results are shown in Table 4 for insulin content.
Table 4 is micronized influence of the tetrahydro curcumin to spontaneous diabetes B db/db mice serum insulin
| Group | N (only) | Dosage (mg/kg) | Insulin content (ug/L) |
| Normal group | 10 | —— | 0.11±0.02** |
| Model group | 7 | —— | 1.00±0.47 |
| Tetrahydro curcumin group | 7 | 100 | 1.43±0.76 |
| It is micronized tetrahydro curcumin group | 6 | 100 | 2.02±0.81* |
Note: P < 0.05 *, P < 0.01 * * compared with model group；The 0.05 ##P < 0.01 of #P < compared with tetrahydro curcumin group
As shown in Table 4, the serum insulin content for being micronized tetrahydro curcumin 100mg/kg dosage group is significantly raised, there is system
Meter learns meaning (P < 0.05), illustrates under identical dosage, and compared with tetrahydro curcumin group, the present invention is micronized tetrahydro ginger
Flavine is more advantageous to promotion insulin secretion, improves internal insulin content, promotes sugar decomposition.
6) influence of the micronization tetrahydro curcumin to insulin in spontaneous diabetes B db/db mice pancreatic tissue
Tetrahydro curcumin is micronized to be immunized on what insulin in spontaneous diabetes B db/db mice pancreatic tissue influenced
Groupization observation result is shown in Fig. 3.Seen by Fig. 3, normal group (A): insulin positive product is in sepia, is located at islet cells endochylema
Interior, arrangement is close；Model group (B): insulin positive product is dispersed in light brown or shallow sepia and is distributed in islet cells endochylema
It is interior, it arranges more loose and faint；Tetrahydro curcumin (100mg/kg) group (C): insulin positive product is in shallow sepia or palm fibre
Brown is located in islet cells endochylema, arranges closer, positive products dyeing enhancing；The present invention is micronized tetrahydro curcumin
(100mg/kg) group (D): insulin positive product is in shallow sepia or sepia, is located in islet cells endochylema, is arranged tighter
Close, positive products dyeing significantly increases.Test result explanation, compared with tetrahydro curcumin, the present invention is micronized tetrahydro curcumin
It is more advantageous to promotion insulin secretion, has better therapeutic effect to spontaneous diabetes B db/db mouse.
7) influence of the micronization tetrahydro curcumin to GLP-1 in spontaneous diabetes B db/db mice pancreatic tissue
It is micronized the immune group that tetrahydro curcumin influences GLP-1 in spontaneous diabetes B db/db mice pancreatic tissue
Change observation result and sees Fig. 4.From fig. 4, it can be seen that normal group (A): GLP-1 positive products are in sepia, are distributed mainly on pancreas islet periphery
In cell cytosol, arrangement is close；Model group (B): GLP-1 positive products are in sepia, are mainly dispersed in that be distributed in pancreas islet periphery thin
In born of the same parents' endochylema, arrange loose；Tetrahydro curcumin (100mg/kg) group (C): GLP-1 positive products be in shallow sepia or sepia,
It is mainly dispersed in and is distributed in the cell cytosol of pancreas islet periphery, arrangement is more loose, and positive products staining cell increases；Present invention micronization
Tetrahydro curcumin (100mg/kg) group (D): GLP-1 positive products are in shallow sepia or sepia, are mainly dispersed in and are distributed in pancreas islet
In the cell cytosol of periphery, arrangement is closer, and positive products staining cell increased significantly.Test result explanation, with tetrahydro curcumin
It compares, the present invention is micronized tetrahydro curcumin and is more advantageous to raising GLP-1 protein expression, has protective effect to islet B cell, right
Spontaneous diabetes B db/db mouse has better therapeutic effect.
To sum up, micronization tetrahydro curcumin of the invention, drug particle size is small, is conducive to discharge and absorb.With tetrahydro turmeric
Element, micronization tetrahydro curcumin of the invention has the effect of better hypoglycemic and reducing blood lipid, meanwhile, it is capable to improve GLP-1
Protein expression promotes insulin secretion, has better protective effect to insulin B, has better effect for treatment diabetes B
Fruit.
Claims (8)
1. a kind of micronization tetrahydro curcumin, it is characterised in that: the particle size range of the micronization tetrahydro curcumin is 1~100 μ
m。
2. micronization tetrahydro curcumin according to claim 1, it is characterised in that: the grain of the micronization tetrahydro curcumin
Diameter range is 1~50 μm.
3. the preparation method of micronization tetrahydro curcumin of any of claims 1 or 2, it is characterised in that: it includes the following steps:
The medicinal vibration type ultramicro disintegrator of tetrahydro curcumin raw material is crushed into 5~60min, obtains tetrahydro curcumin micro mist.
4. preparation method according to claim 3, it is characterised in that: it includes the following steps:
The medicinal vibration type ultramicro disintegrator of tetrahydro curcumin raw material is crushed into 15min, controls 25 DEG C of temperature hereinafter, obtaining tetrahydro
Curcumin micro-powder.
5. micronization tetrahydro curcumin of any of claims 1 or 2 is preparing the purposes in hypoglycemic drug.
6. purposes of the micronization tetrahydro curcumin of any of claims 1 or 2 in the drug of preparation reducing blood lipid.
7. purposes of the micronization tetrahydro curcumin of any of claims 1 or 2 in the drug of preparation treatment diabetes.
8. purposes according to claim 5, it is characterised in that: the diabetes are spontaneous diabetes B.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732292A (en) * | 2010-01-25 | 2010-06-16 | 四川省中医药科学院 | Novel application of tetrahydrocurcumin |
| CN102526004A (en) * | 2010-01-25 | 2012-07-04 | 四川省中医药科学院 | New use of tetrahydrocurcumin |
| CN102552225A (en) * | 2010-01-25 | 2012-07-11 | 四川省中医药科学院 | Novel application of tetrahydrocurcumin |
| CN104739813A (en) * | 2013-12-26 | 2015-07-01 | 四川省中医药科学院 | New tetrahydrocurcumin uses |
-
2019
- 2019-05-31 CN CN201910471166.4A patent/CN110025579A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732292A (en) * | 2010-01-25 | 2010-06-16 | 四川省中医药科学院 | Novel application of tetrahydrocurcumin |
| CN102526004A (en) * | 2010-01-25 | 2012-07-04 | 四川省中医药科学院 | New use of tetrahydrocurcumin |
| CN102552225A (en) * | 2010-01-25 | 2012-07-11 | 四川省中医药科学院 | Novel application of tetrahydrocurcumin |
| CN104739813A (en) * | 2013-12-26 | 2015-07-01 | 四川省中医药科学院 | New tetrahydrocurcumin uses |
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Application publication date: 20190719 |