CN101015597A - Application of magnolia bark preparation in preparing medicine for treating diabetes and obesity - Google Patents

Application of magnolia bark preparation in preparing medicine for treating diabetes and obesity Download PDF

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Publication number
CN101015597A
CN101015597A CN 200710055256 CN200710055256A CN101015597A CN 101015597 A CN101015597 A CN 101015597A CN 200710055256 CN200710055256 CN 200710055256 CN 200710055256 A CN200710055256 A CN 200710055256A CN 101015597 A CN101015597 A CN 101015597A
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magnoliae officinalis
cortex magnoliae
preparation
magnolia bark
ethanol
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付学奇
赵志壮
李青山
刘玉珊
张鸿义
邢述
徐越驰
李莹
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Jilin University
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Jilin University
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Abstract

The application of Magnolia officinalis preparation for the production of medicaments for treating diabetes and obesity belongs to the field of medicinal application. The Magnolia officinalis preparation is extracted from Magnolia officinalis by soaking in ethanol with magnolol and honokiol as main ingredients. The preparation has effects of in-vitro inhibiting the activity of protein-tyrosine phosphatase 1B (PTP1B) and reducing blood sugar level in rat model of type 2 diabetes. The preparation can be made into powder, pill, capsule, tablet, oral liquid and injection. It can be used for treating diabetes, obesity, and diseases related to PTP1B.

Description

The application of magnolia bark preparation in preparation treatment diabetes and obesity drug
Technical field
The invention belongs to the medical usage technical field of material, the particularly application of magnolia bark preparation in the Chinese medicine preparation of preparation treatment diabetes and obesity.
Background technology
Diabetes mainly are divided into two types clinically: type i diabetes and type ii diabetes, wherein type ii diabetes accounts for 80%~90% of morbidity sum, the whole world surpasses 100,000,000 people and suffers from type ii diabetes, the cause of disease of type ii diabetes mainly is impedance and the B cell excreting insulin relative deficiency of body tissue to insulin, and the insulin impedance is meant that the target organ of insulin action or target tissue such as liver, muscle, fatty tissue etc. are lower than the normal level of expectation to the biologically of a certain amount of insulin.
Though have some medicines to be used for the treatment of type ii diabetes at present clinically, all have some toxic and side effects.For example, thought a class medicine of most promising treatment type ii diabetes in the past, present thiazolidinedione (tetrahydro-thiazoles diketone) the class medicine that still uses clinically, they are to activate the γ receptor by the peroxidase proliferation to increase the class medicine that the adipose cell differentiation and proliferation improves insulin sensitivity, have now found that they cause weight in patients to increase usually and have some other side effect, therefore are badly in need of safe and effective target agent at present.
The numerous protein tyrosine phosphatase is arranged in the animal body, they are controlling the phosphorylation of protein-tyrosine with tyrosine kinase, these enzymes play an important role in the signal conductive process in cell, and close getting in touch all arranged with many pathological phenomenons, Protein Tyrosine Phosphatases 1B (Protein TyrosinePhosphatase1B wherein, PTP1B) be one of the most popular object of study, because be the important target of a treatment type ii diabetes and obesity to all providing stem-winding evidence: PTP1B with external research in the body of PTP1B in recent years, therefore the inhibition to PTP1B is a kind of extremely promising therapy for the treatment of type ii diabetes and obesity.
PTP1B is the Protein Tyrosine Phosphatases in a kind of born of the same parents, is positioned at endoplasmic reticulum.It is separated in people's placenta cells in 1988 by Nobel's physiology and the medical science prize Edmond.H.Fischer of winner obtain for the first time.PTP1B is made up of 435 amino acid residues, molecular weight 49666Da, and its wide expression all in various cells comprises picture liver, muscle and these tissues as the important regulator of insulin metabolism of fat.Research in recent years is verified, and PTP1B is the negative regulator of a specificity of insulin signaling, and the mice of PTP1B gene knockout have extremely strong sensitivity to islets of langerhans, and feeds still not weight increase for a long time with higher fatty acid foodstuff; Find also that in addition can recover the sensitivity of diabetic mice to insulin with the PTP1B antisense oligonucleotide, this has also illustrated the effect of PTP1B under diabetic disease states; The activity of PTP1B is higher by 30% than normally going in the diabetic body in addition.These studies show that, PTP1B can regulate insulin signaling and this PTP1B be had the important clinical application prospect as the mode that target suppresses on treatment type ii diabetes and obesity.
In recent years, a lot of research worker both domestic and external are all being sought optionally PTP1B inhibitor always, though special, effective and safe non-peptide inhibitor does not find that also the research of PTP1B inhibitor has obtained certain progress.Most of PTP1B inhibitor of having found at present are peptide class or the stronger material of toxicity, and for example nonselective PTP inhibitor vanadate and pervanadate etc. can't be developed as medicine.Other is as Chinese patent CN1794989A; the PTP1B inhibitor of being mentioned is N-(((((1; the 3-thiazol-2-yl) sulfonyl phenyl carbonyl amino)))) phenylalanine derivative and related compound need obtain complex manufacturing by the multistep chemosynthesis.Screening PTP1B inhibitor is one of most promising method from the Chinese medicine resource, the now existing PTP1B inhibitor that separation and Extraction obtains from natural plants such as Chinese medicine, as Chinese patent CN1521157A, in plant Herba Ardisiae Japonicae and Herba Hyperici Erecti, separate having obtained a series of PTP1B mortifier 1,4-benzoquinone compounds and derivant thereof.
Summary of the invention
The technical problem to be solved in the present invention is that the new purposes of exploitation Chinese medicine Cortex Magnoliae Officinalis promptly, is that raw material is made the magnolia bark preparation that is used for the treatment of diabetes and obesity with Cortex Magnoliae Officinalis or magnolia officinalis rehd.et wils.var.biloba rehd.et wils..
Magnolia bark preparation of the present invention is to extract the natural product that obtains from the plant Cortex Magnoliae Officinalis, Cortex Magnoliae Officinalis is dry dried bark, root bark and the branch skin of Magnoliacea plant Cortex Magnoliae Officinalis (Magnolia of ficinalisRehd.et Wils.) or magnolia officinalis rehd.et wils.var.biloba rehd.et wils. (Magnolia of ficinalisRehd.etWils.Var.biloba Rehd.et Wils.), be traditional Chinese medicine, its main component is magnolol and honokiol.
The said magnolia bark preparation of the present invention is to extract from Cortex Magnoliae Officinalis by the method for ethanol or water logging bubble to obtain a kind of preparation, its main component is magnolol and honokiol, this magnolia bark preparation has tangible blood sugar reducing function to the type ii diabetes rat model in vivo in the activity of external energy Profilin matter tyrosine phosphatase 1B.
The said magnolia bark preparation of the present invention also can be Cortex Magnoliae Officinalis water decoction, Cortex Magnoliae Officinalis powder, Cortex Magnoliae Officinalis extractum, Cortex Magnoliae Officinalis pill, Cortex Magnoliae Officinalis capsule, Cortex Magnoliae Officinalis tablet, Cortex Magnoliae Officinalis oral liquid or Cortex Magnoliae Officinalis injection.They can be used as the medicine or the drug regimen of preparation treatment diabetes, obesity, also can be used as the medicine or the drug regimen composition of preparation treatment and Protein Tyrosine Phosphatases 1B relevant disease.
What the preparation method of magnolia bark preparation was concrete is:
(1) will grind after the Cortex Magnoliae Officinalis drying, filter, obtain Cortex Magnoliae Officinalis dry powder by the 40-60 mesh sieve.
(2) with the ethanol of Cortex Magnoliae Officinalis dry powder and 70%-100% by volume 1: 3.5-4.5 soaks and stirs, and stirring revolution is 60-300 rev/min, and 1-3 hour, filter and remove residue, obtain the soak with ethanol liquid of Cortex Magnoliae Officinalis.Ethanol evaporation in the solution that obtains is removed, obtained thick Cortex Magnoliae Officinalis extractum.
(3) extractum is heated 80-150 ℃ of drying to remove remaining ethanol; Again that exsiccant ethanol extraction is soluble in water, through the fill sterilization, make Cortex Magnoliae Officinalis oral liquid or Cortex Magnoliae Officinalis injection.
By the preparation process of above-mentioned magnolia bark preparation, after (1) step, just made the Cortex Magnoliae Officinalis powder through packing; After (2) step, extractum is heated 80-150 ℃ of drying and remove remaining ethanol; Again exsiccant ethanol extraction is pulverized, added adjuvant, make Cortex Magnoliae Officinalis capsule, Cortex Magnoliae Officinalis pill or Cortex Magnoliae Officinalis tablet again.Said adjuvant is the adjuvant that adds common making pill, tablet or capsule in Cortex Magnoliae Officinalis extractum, as Mel, just can make the Cortex Magnoliae Officinalis pill; As add starch, cyclodextrin and glucose etc. and just can make tablet and capsule; In (3) step, exsiccant ethanol extraction (Cortex Magnoliae Officinalis extractum) is weighed, W: V=1: 10-20 is dissolved in the tween of 2%-10% in proportion, and such as Tween20, in the aqueous solution, this liquid is the Cortex Magnoliae Officinalis antihypelipidemic preparation of preparation.
With Cortex Magnoliae Officinalis or Cortex Magnoliae Officinalis dry powder and distilled water, pure water or deionized water by volume 1: 2-4 soaks and stirs, and stirring revolution is 60-300 rev/min, after 1-3 hour, filters and removes residue, obtains the Cortex Magnoliae Officinalis water decoction.
Above-mentioned Cortex Magnoliae Officinalis water decoction is heated to 95-100 ℃ removes moisture; Treat bone dry, more exsiccant water extract is pulverized; Exsiccant water extract is weighed, in proportion W: V=1: 10-20 is dissolved in the tween of 2%-10%, and such as Tween20, in the aqueous solution, this liquid is the Cortex Magnoliae Officinalis antihypelipidemic preparation of preparation.
The magnolia bark preparation of the present invention's preparation, can be in the activity of vitro inhibition Protein Tyrosine Phosphatases 1B (PTP1B), and the type ii diabetes rat model had tangible blood sugar reducing function, can be used as a series of medicine or drug regimen compositions with the PTP1B relevant disease such as treatment diabetes, obesity.
High performance liquid chromatography (HPLC) detects:
Magnolia bark preparation is carried out high performance liquid chromatography detect, testing conditions is as follows: mobile phase is for containing 20% methanol in water, the C18 chromatographic column, and 20 ℃ of column temperatures, the detection wavelength is 254nm.By comparing the HPLC testing result of magnolol and honokiol standard substance and magnolia bark preparation sample, the main component that proves this magnolia bark preparation is magnolol and honokiol.
The active mensuration of PTP1B
Measuring principle and reaction system:
PTP1B is a kind of phosphatase, and it can make the protein dephosphorylation of phosphorylation.Adopt molecular biology method to make up people's PTP1B catalyst structure domain expression carrier, at the catalyst structure domain of expression in escherichia coli PTP1B, purified back is a substrate with p-nitrophenyl disodic alkaliine (pNPP), measures the activity of PTP1B.PNPP can be become paranitrophenol by the PTP1B dephosphorylation, and it is yellow that color is, and comes the situation of change of indirect detection enzymatic activity by the variation that detects 410nm place absorbance value.The mensuration system is as follows: 25mM morpholino propane sulfonic acid (MOPS) pH7.0,1mg/ml bovine serum albumin (BSA), 1mM dithiothreitol, DTT (DTT), 0.1mM disodium EDTA (EDTA), 0.1M sodium chloride (NaCl), 5nM PTP1B, the overall reaction system is 100 μ l, at room temperature react 10min, measure the changing value of light absorption at the 410nm place.
Magnolia bark preparation is to the assay method of PTP1B inhibitory action (being to add the absorption value that records behind the magnolia bark preparation of each Concentraton gradient in the reaction system):
Various materials generally pass through to measure its half-inhibition concentration (IC to the inhibitory action of PTP1B 50) weigh, for this magnolia bark preparation, (be IC to the inhibitory action of PTP1B 50) then weigh with its dry weight.
Magnolia bark preparation is diluted by 1/2 gradient, the sample of each Concentraton gradient after the dilution is added in the reaction system of PTP1B determination of activity, wherein the volume of magnolia bark preparation is 10 μ l, measures the room temperature condition changing value of the light absorption of reaction 10min down, according to formula:
(1-A/A 0)×100%
The numerical value that calculates is inhibition percent, and wherein A adds the absorption value that records behind the magnolia bark preparation of each Concentraton gradient, A in the reaction system 0The absorption value that records when not adding the Cortex Magnoliae Officinalis preparation in the reaction system.When inhibition percent reached 50%, the concentration of pairing magnolia bark preparation was IC 50
Measure the inhibition ability of each diluted concentration of magnolia bark preparation to PTP1B, and the pairing suppression ratio mapping of each concentration that will obtain, IC can be obtained 50Curve.According to IC 50Curve is extrapolated the IC of this magnolia bark preparation 50Value is 0.00125g/ml (this quality is reduced Cortex Magnoliae Officinalis dry powder quality).
The specific embodiment
Embodiment 1
Get the exsiccant Cortex Magnoliae Officinalis skin of 600g and grind, filter, obtain Cortex Magnoliae Officinalis dry powder 500g through 40 mesh sieves.
Embodiment 2
The Cortex Magnoliae Officinalis dry powder 350g of embodiment 1 is soaked with the 1500ml dehydrated alcohol and stir, stirring revolution is 60 rev/mins, filters with 80 orders and 120 mesh sieves respectively after 3 hours and removes residue.The filtrate that obtains is removed ethanol by rotary evaporating device evaporation under 70-80 ℃, obtain thick Cortex Magnoliae Officinalis extractum.
Also can directly use the Chinese medicine Cortex Magnoliae Officinalis to soak with ethanol and stir, through filtering residue, ethanol is removed in evaporation, obtains thick Cortex Magnoliae Officinalis extractum.
Embodiment 3
80 ℃ of dryings of Cortex Magnoliae Officinalis extractum heating of embodiment 2 are removed remaining ethanol, treat the extractum bone dry, again that exsiccant ethanol extraction is soluble in water, through the fill sterilization, make Cortex Magnoliae Officinalis oral liquid or Cortex Magnoliae Officinalis injection.
Embodiment 4
150 ℃ of dryings of Cortex Magnoliae Officinalis extractum heating of embodiment 2 are removed remaining ethanol; Treat extractum bone dry (caking), more exsiccant ethanol extraction is pulverized, pour into and obtain the Cortex Magnoliae Officinalis capsule in the capsule.
150 ℃ of dryings of Cortex Magnoliae Officinalis extractum heating of embodiment 2 are removed remaining ethanol; Treat the extractum bone dry, exsiccant ethanol extraction pulverized that adding starch, cyclodextrin and the glucose measured usually is adjuvant, makes the Cortex Magnoliae Officinalis tablet by the tablet machine tabletting.
150 ℃ of dryings of Cortex Magnoliae Officinalis extractum heating of embodiment 2 are removed remaining ethanol; Treat the extractum bone dry, exsiccant ethanol extraction is pulverized, add adjuvants such as normally used Mel, make the Cortex Magnoliae Officinalis pill.
Embodiment 5
Get exsiccant Cortex Magnoliae Officinalis skin and grind, filter, obtain Cortex Magnoliae Officinalis dry powder through 40 mesh sieves.400g Cortex Magnoliae Officinalis dry powder (or 600g Chinese medicine Cortex Magnoliae Officinalis) is soaked in the 1500ml distilled water and stir, stirring revolution is 300 rev/mins, after 1 hour (or 3 hours), filters and removes residue, obtains the Cortex Magnoliae Officinalis water decoction.
Embodiment 6
The Cortex Magnoliae Officinalis extractum of embodiment 2 is placed on is heated to 80-150 ℃ in the drying baker to evaporate remaining ethanol, till the extractum bone dry.After ethanol extraction behind the bone dry weighed in proportion W/V=1/10 be dissolved in 5% Tween20 (V/V) aqueous solution, obtain the Cortex Magnoliae Officinalis antihypelipidemic preparation.
Embodiment 7
The Cortex Magnoliae Officinalis water decoction of embodiment 5 is heated to 95-100 ℃ of drying removes moisture; Treat bone dry, more exsiccant water extract is pulverized; Exsiccant water extract is weighed, in proportion W: V=1: 20 are dissolved in 10% the Tween20 aqueous solution, and this liquid is the Cortex Magnoliae Officinalis antihypelipidemic preparation of preparation.
Embodiment 8
Study its blood sugar reducing function with embodiment 6 prepared magnolia bark preparations to the type ii diabetes rat model:
This experiment is finished by the Bethune of Jilin University medical college pharmacology teaching and research room, wherein laboratory animal is the Wistar rat, male, be divided into 4 groups, be respectively matched group (feminine gender), type ii diabetes model group (positive), type ii diabetes model administration (magnolia bark preparation) group and type ii diabetes model insulin injection group.The medication of type ii diabetes model insulin injection group is lumbar injection (30U/kg), and all the other the 3 groups method administrations by the filling stomach, wherein matched group and model group give the normal saline of equal volume.Dosage is 10ml/kg body weight (being equivalent to 25g crude drug/kg body weight), administration every day 1 time, and table 1 is successive administration measured variation of respectively organizing blood glucose value after 9 days.
Table 1 magnolia bark preparation is to the blood sugar reducing function of type ii diabetes rat model
Figure A20071005525600091
Credit is analysed by statistics, and successive administration is after 9 days, and tangible reduction has taken place the rat blood sugar value of type ii diabetes model administration (magnolia bark preparation) group, compares with type ii diabetes model group (positive) blood glucose value, there were significant differences ( *And near the blood glucose value of normal control group (feminine gender), magnolia bark preparation has tangible blood sugar reducing function to the type ii diabetes rat model P<0.05).

Claims (8)

1, the application of a kind of magnolia bark preparation in preparation treatment diabetes and obesity drug, with the Cortex Magnoliae Officinalis is primary raw material, it is characterized in that said magnolia bark preparation is Cortex Magnoliae Officinalis water decoction, Cortex Magnoliae Officinalis powder, Cortex Magnoliae Officinalis extractum, Cortex Magnoliae Officinalis pill, Cortex Magnoliae Officinalis capsule, Cortex Magnoliae Officinalis tablet, Cortex Magnoliae Officinalis oral liquid or Cortex Magnoliae Officinalis injection; They are as the medicine or the drug regimen of preparation treatment diabetes, obesity, or conduct prepares the medicine or the drug regimen composition for the treatment of with Protein Tyrosine Phosphatases 1B relevant disease.
2, according to the application of the described magnolia bark preparation of claim 1 in preparation treatment diabetes and obesity drug, it is characterized in that, will grind after the Cortex Magnoliae Officinalis drying, filter, obtain Cortex Magnoliae Officinalis dry powder by the 40-60 mesh sieve.
3, the application in preparation treatment diabetes and obesity drug according to claim 1 or 2 described magnolia bark preparations, it is characterized in that, comprise the ethanol of Cortex Magnoliae Officinalis or Cortex Magnoliae Officinalis dry powder and 70%-100% by volume 1: 3.5-4.5 soaks and stirs, stirring revolution is 60-300 rev/min, after 1-3 hour, filter and remove residue, obtain the soak with ethanol liquid of Cortex Magnoliae Officinalis; Ethanol evaporation in the solution that obtains is removed, obtained thick Cortex Magnoliae Officinalis extractum.
4, the application in preparation treatment diabetes and obesity drug according to claim 1 or 2 described magnolia bark preparations, it is characterized in that, comprise Cortex Magnoliae Officinalis or Cortex Magnoliae Officinalis dry powder and distilled water, pure water or deionized water by volume 1: 2-4 soaks and stirs, stirring revolution is 60-300 rev/min, after 1-3 hour, filter and remove residue, obtain the Cortex Magnoliae Officinalis water decoction.
5, according to the application of the described magnolia bark preparation of claim 3 in preparation treatment diabetes and obesity drug, it is characterized in that, comprise that extractum is heated 80-150 ℃ of drying removes remaining ethanol; Again that exsiccant ethanol extraction is soluble in water, through the fill sterilization, make Cortex Magnoliae Officinalis oral liquid or Cortex Magnoliae Officinalis injection.
6, according to the application of the described magnolia bark preparation of claim 3 in preparation treatment diabetes and obesity drug, it is characterized in that, comprise that extractum is heated 80-150 ℃ of drying removes remaining ethanol; Again exsiccant ethanol extraction is pulverized, added adjuvant, make Cortex Magnoliae Officinalis capsule, Cortex Magnoliae Officinalis pill or Cortex Magnoliae Officinalis tablet again.
7, the application in preparation treatment diabetes and obesity drug according to claim 1 or 2 described magnolia bark preparations, it is characterized in that, comprise the ethanol of Cortex Magnoliae Officinalis or Cortex Magnoliae Officinalis dry powder and 70%-100% by volume 1: 3.5-4.5 soaks and stirs, stirring revolution is 60-300 rev/min, after 1-3 hour, filter and remove residue, obtain the soak with ethanol liquid of Cortex Magnoliae Officinalis; Ethanol evaporation in the solution that obtains is removed, obtained thick Cortex Magnoliae Officinalis extractum; Cortex Magnoliae Officinalis extractum is weighed, in proportion W: V=1: 10-20 is dissolved in the Tween solution of 2%-10%, and this liquid is the Cortex Magnoliae Officinalis antihypelipidemic preparation of preparation.
8, the application in preparation treatment diabetes and obesity drug according to claim 1 or 2 described magnolia bark preparations, it is characterized in that, comprise Cortex Magnoliae Officinalis or Cortex Magnoliae Officinalis dry powder and distilled water, pure water or deionized water by volume 1: 2-4 soaks and stirs, stirring revolution is 60-300 rev/min, after 1-3 hour, filter and remove residue, obtain the Cortex Magnoliae Officinalis water decoction; The Cortex Magnoliae Officinalis water decoction is heated to 95-100 ℃ removes moisture; Treat bone dry, more exsiccant water extract is pulverized; Exsiccant water extract is weighed, in proportion W: V=1: 10-20 is dissolved in the Tween solution of 2%-10%, and this liquid is the Cortex Magnoliae Officinalis antihypelipidemic preparation of preparation.
CN 200710055256 2007-01-23 2007-01-23 Application of magnolia bark preparation in preparing medicine for treating diabetes and obesity Pending CN101015597A (en)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102240274A (en) * 2011-05-13 2011-11-16 吉林大学 Application of magnolol and honokiol in protein tyrosine phosphatase 1B inhibitor
CN102512403A (en) * 2011-12-06 2012-06-27 中国中医科学院西苑医院 Application of honokiol in pharmacy, and medicine used for treating type II diabetes mellitus
CN102846712A (en) * 2012-08-31 2013-01-02 格特生物制药(天津)有限公司 Magnolia cortex sodium bicarbonate tablet for livestock and preparation method thereof
CN103301198A (en) * 2013-06-26 2013-09-18 瑞普(天津)生物药业有限公司 Mangnolia officinalis total-effect ingredient obtaining method and preparation method of ingredient
CN103976433A (en) * 2014-04-17 2014-08-13 五河县鲲鹏食品饮料有限公司 Magnolia officinalis blood sugar-reduction health beverage and preparation method thereof
CN104736147A (en) * 2012-05-29 2015-06-24 尤妮金公司 Compositions and methods for managing weight

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102240274A (en) * 2011-05-13 2011-11-16 吉林大学 Application of magnolol and honokiol in protein tyrosine phosphatase 1B inhibitor
CN102512403A (en) * 2011-12-06 2012-06-27 中国中医科学院西苑医院 Application of honokiol in pharmacy, and medicine used for treating type II diabetes mellitus
KR20200121895A (en) * 2012-05-29 2020-10-26 유니젠, 인크. Compositions and methods for managing weight
CN108434197B (en) * 2012-05-29 2021-11-12 尤妮金公司 Compositions and methods for weight management
CN104736147A (en) * 2012-05-29 2015-06-24 尤妮金公司 Compositions and methods for managing weight
KR102309488B1 (en) 2012-05-29 2021-10-06 유니젠, 인크. Compositions and methods for managing weight
CN107281490A (en) * 2012-05-29 2017-10-24 尤妮金公司 Composition and method for control body weight
CN107281490B (en) * 2012-05-29 2021-08-20 尤妮金公司 Compositions and methods for weight management
CN104736147B (en) * 2012-05-29 2018-05-18 尤妮金公司 For the composition and method of control body weight
CN108434197A (en) * 2012-05-29 2018-08-24 尤妮金公司 Composition and method for control body weight
CN102846712A (en) * 2012-08-31 2013-01-02 格特生物制药(天津)有限公司 Magnolia cortex sodium bicarbonate tablet for livestock and preparation method thereof
CN103301198A (en) * 2013-06-26 2013-09-18 瑞普(天津)生物药业有限公司 Mangnolia officinalis total-effect ingredient obtaining method and preparation method of ingredient
CN103301198B (en) * 2013-06-26 2018-02-02 瑞普(天津)生物药业有限公司 A kind of bark of official magnolia imitates composition preparation method and preparation method thereof entirely
CN103976433B (en) * 2014-04-17 2015-10-28 五河县鲲鹏食品饮料有限公司 A kind of bark of official magnolia blood sugar reducing health beverage and preparation method thereof
CN103976433A (en) * 2014-04-17 2014-08-13 五河县鲲鹏食品饮料有限公司 Magnolia officinalis blood sugar-reduction health beverage and preparation method thereof

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