CN1446549A - Use of licorice and its extract for treating osteoporosis - Google Patents
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Abstract
An application of liquorice root and its extracts (glycyrrhizin, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, liquiriligenin, iso-liquiniligenin and liquorice polyose) in preventing and treating osteoporosis is disclosed.
Description
The present invention relates to the new purposes of Chinese medicine Radix Glycyrrhizae and Radix Glycyrrhizae extract protect against osteoporosis.
Osteoporosis is geratologous heat subject, along with wearing out of world population, the crowd who suffers from osteoporosis is increasing year by year, the old people of the present over-65s of China has accounted for 1.2 hundred million according to statistics, and the patient who suffers from osteoporosis accounts for 90% in these crowds, and therefore, preventing and treating osteoporosis is defying age, life-saving, the very urgent research topic of the assurance people's quality of life.Protect against osteoporosis is not found ideal new drug as yet both at home and abroad at present, though the estrogen that tradition is used, replenish the calcium and the vitamin D use in conjunction has certain curative effect, but still there is a difficult problem on the more therapeutics, in order to solve this difficult problem, in the ideal medicament of seeking osteoporosis from natural drug, hope can be found a kind of new drug of ideal osteoporosis to the member of this seminar always.
By a large amount of animal experiment studies and screening, the dry root and rhizome that we have found Chinese medicine glycyrrhizic legume (Glycyrrhiza uralensis Fisch.) with and the extract triterpenoid compound glycyrrhizin (glycyrrhizin glycyrrhizin or glycyrrhizic acid glycyrrhizicacid) and the enoxolone (glycyrrhetinic acid) of dry root, flavone compound liquiritin (liquiritin or title liquiritin), isoliquiritin (isoliquiritin), glycyrrhizin (liquiriligenin), isoliquiritigenin (iso-liquiriligenin) and Angelica Polysaccharide have the effect of better prevention osteoporosis.The deep said extracted thing that has also proved Radix Glycyrrhizae and Radix Glycyrrhizae has the osteoporotic effect of tangible control, provides a new approach for the mankind solve osteoporosis.
Task of the present invention is with the technology of science the extract of Radix Glycyrrhizae and active ingredient thereof to be made preparation, make said preparation be used for human protect against osteoporosis, said preparation can stop losing of sclerotin, can promote the formation of new bone again, provides new purposes for solving an osteoporotic difficult problem.
The approach that solves this task is to realize like this, choose the dry root and rhizome of glycyrrhizic legume (Glycyrrhizauralensis Fisch.), it is the medicinal part that Chinese medicine is called Radix Glycyrrhizae, add 10 times of water by traditional technology, water is carried three times respectively, filter, be concentrated into content of dispersion 100%, be used for research as licorice water extract, in addition, method by relevant bibliographical information, with Radix Glycyrrhizae is raw material, its relevant chemical constituent glycyrrhizin (glycyrrhizic acid) of purifying out respectively, enoxolone, liquiritin, isoliquiritin, glycyrrhizin, isoliquiritigenin and Angelica Polysaccharide carry out administration research, comparative observation licorice water extract and these seven the pharmacodynamics functions that are subjected to the test product osteoporosis with white mice osteoporosis model and the rat osteoporosis model that this research department sets up then.
The result is as follows: licorice water extract is subjected to test product that the osteoporotic effect of significant prevention laboratory animal is all arranged with these seven.Wherein Radix Glycyrrhizae and glycyrrhizin (glycyrrhizic acid) prevent the osteoporotic effect highly significant of animal.Liquiritin and Angelica Polysaccharide effect are taken second place, and other several kinds also have certain curative effect.
Embodiment:
(Glycyrrhizin is the effective ingredient of Chinese medicine Radix Glycyrrhizae GL) to glycyrrhizic acid, has the effect of antiinflammatory, antiallergic and hepatoprotective
[1,2], in recent years, found that not only osteoporosis can take place primary biliary cirrhosis (PBC) patient, the hepatic disease of other reason also can cause
[3,4], therefore, the osteoporosis of control due to the hepatic disease comes into one's own day by day
[5,6]This research is set up the animal model of hepatic fibrosis with white mice, inquires into the situation of bone loss in chronic hepatopathy, and when observing the glycyrrhizic acid hepatoprotective, whether the effect that reduces bone loss is arranged.40 of the regular grade Kunming kind white mice that 1 materials and methods, 1.1 animal the court Experimental Animal Center provide, body weight 20-22g, ♀ ♂ half and half is by body weight principle of reciprocity random packet.1.2 medicine carbon tetrachloride (analytical pure): purchase in Guangzhou Chemical Reagent Factory, lot number is 980402-25, is made into 40% carbon tetrachloride Oleum Arachidis hypogaeae semen with pure edible peanut oil during experiment.
Colchicine (purchase in shanghai Medicine reagent company for colchicine, CL) German import packing, and the time spent is made into 0.01mg.ml by lot number 991010
-1Aqueous solution.
Glycyrrhizic acid Mongolia Radix Glycyrrhizae is extracted 10mg.ml
-1, provide by Medicines Science and Technology Development Center, Guangdong Medical College (.1.3 instrument and reagent WFX-1D atomic absorption spectrophotometer (production of second optical instrument factory, Beijing); Prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit AE240 electronic balance (prunus mume (sieb.) sieb.et zucc. Teller-Shanghai branch company of Tuo benefit instrument company), LEICA QWIN image analyzer (German Lycra company), UV-3101PC scanning spectrophotometer (day island proper Tianjin Co., Ltd. of Instrument and Equipment Company), amino transaminase (AST/GOT) testing cassete of aspartic acid is all purchased and is built up bio-engineering research institute in Nanjing, alanine aminotransferase (ALT/GPT) testing cassete is purchased the kind city biochemical reagents factory in the Ningbo City, and total protein (TP) liquid reagent box and albumin (Alb) test kit are all purchased in Beijing Zhongsheng Biological Engineering High Technology Company.1.4 getting above-mentioned mice, experimental technique is divided into 4 groups at random, 10 every group, and ♀ ♂ half and half, sub-cage rearing, the A group is given N.S 10ml.kg
-1Subcutaneous injection, first dose doubles, and 5d injection 1 time in continuous 5 weeks, is given N.S 10ml.kg after the injection
-1Irritate stomach, qd, continuous 6 weeks; The B group is given 40% carbon tetrachloride peanut oil solution by 10ml.kg
-1Subcutaneous injection, first dose doubles, and 5d injection 1 time in continuous 5 weeks, is given N.S by 10ml.kg after the injection
-1Irritate stomach, qd, continuous 6 weeks; The C group gives CCl by the B group with method
40.01mg.kg is pressed in the back
-1Give Colchicum autumnale solution; The D group is pressed the B group with method injection CCl
4100mg.kg is pressed in the back
-1Give glycyrrhizic acid solution.Observe and respectively organize mice feed, drinking-water, active situation and fur variation every day in experimentation, 7d weighs 1 time, in the carbon tetrachloride of all stopping using in the 5th week, continues 1 week of administration, plucked eyeball respectively in second day and get blood after the last administration, separation of serum is made biochemical analysis; Get liver,kidney,spleen and thymus is weighed, weigh after the right femur drying, the content of trace element and hydroxyl proline (Hyp) in the bone is measured in the acid dissolving; Leftlobe of liver is liquid-solid fixed with Bo Shi, paraffin embedding, and section, HE and VG (Van Gieson) dyeing back malingering is looked into.1.5 observation index and assay method (1) are to the observation of white mice ordinary circumstance and body weight.(2) press document
[7]Measure the content of bone hydroxyproline.(3) press document
[8]Detect serological index, reitman-frankel method is measured the activity of ALT (glutamate pyruvate transaminase), AST (glutamic oxaloacetic transaminase, GOT), and biuret method measures serum T B (total protein) and the bromocresol green method is measured serum Alb (albumin) content.(4) get acid dissolving after the right side of mice femur drying, measure Ca with atomic absorption spectrophotometer
2+, Cu
2+, Zn
2+, Fe
2+, Mg
2+Content.(5) press document
[9] [10]Observe hepatic tissue and reach pathological change under the mirror substantially, hepatopathy variation is estimated for 4 grades.(6) judgement of the relative quantity of hepatic tissue collagen fiber: the specific stain of VG collagen, press document and judge the collagen fiber hyperplasia degree with semi-quantitative method
[9]1.6 the statistical procedures experimental data adopts X ± S to represent that group difference is checked with t, the significance of difference is represented with following sign respectively: compare with the A group: *: P＜0.05; *: P＜0.01; Compare with the B group: Δ: P＜0.05 * *: P＜0.001; Δ Δ: P＜0.01; Δ Δ Δ: P＜0.001;＜0.01) semi-quantitative standards is judged the rank test of employing grade.2 results
2.1 2 dead mouses of B group only in the experiment of ordinary circumstance and body weight change behind the mice chronic hepatic injury.Each body weight change of organizing mice the results are shown in Table 1, by table 1 as seen, and CCl
4The body weight of contamination one week back B, C, D three treated animals all obviously alleviates (P＜0.05) than the A group, the B group to the 6th all body weight obviously than A, C, three groups of 0.01mg.kg of D
-1Low (P＜0.05), and the body weight of two groups of C, D is unlike A group low (P＞0.05), so think that two kinds of medicines are to reduction CCl
4Toxicity have certain effect.
Respectively organize body weight change result (X ± S, n=10) (g) Group Original First Second Third Forth Firth Sixth of mice behind the table 1 mice chronic hepatic injury
Weight week week week week week weekA 19.4 ± 1.4 24.2 ± 1.8 29.5 ± 4.9 31.7 ± 5.1 32. ± 5.3 33.2 ± 6.0 34.1 ± 6.1B 20 ± 1.6 22.3 ± 1.9
*26.9 ± 4.7 27.9 ± 3.4 30. ± 2.6 28.3 ± 1.9 28.7 ± 1.9
*C 20 ± 1.1 21.3 ± 1.3
*26.4 ± 2.3 26.7 ± 2.3 28. ± 2.8 30.3 ± 4.1 33.7 ± 3.5
ΔD 20 ± 1.0 19.8 ± 2.0
*26.4 ± 2.5 27.4 ± 3.0 30. ± 5.2 31.8 ± 4.1 33.4 ± 5.4
Δ2.2 glycyrrhizic acid is to CCl
4The B group mouse liver ponderal index (LW=liver weight/body weight * 10) that influences of liver weight exponential sum serum biochemistry index has increased by 76.2% than the A group behind the mouse liver injury, and difference has significance (P＜0.001); The LW of C group is bigger than the A group, but obviously than B group light (P＜0.05), D group LW compares zero difference (P＞0.05) with the A group, but organizes light by 32.4% (P＜0.01) than B.Serum index result shows that serum AST, the ALT of B group mice obviously rise (P＜0.01) than the A group, and two groups of liver enzymes of C, D also raise, but than B group low (P＜0.01), wherein the ALT of D group is than C group low (P＜0.05); The albumin of B group is than A group low (P＜0.01), and also than two groups low of C, D (P＜0.01), A/G value is also organized low (P＜0.05) than C, D, everyly the results are shown in Table 2; Tab 2 glycyrrhizic acids are to CCl
4Influence (the X of liver weight exponential sum serum biochemistry index behind the mouse liver injury
±S，n＝10
)Group LW(g/g) ALT(IU) AST(IU) TP(g/l) Alb(g/1) A/GA 0.42±0.07 54.0±12.6 82.2±16.0 51.4±5.8 24.9±2.7 1.05±0.42B 0.74±0.08
*** 111±16.3
*** 98.2±11.2
** 65.0±9.08
** 17.13±3.01
** 0.37±0.09
**C 0.52±0.13
*Δ 76.0±9.28
*ΔΔ 90.1±19.1
Δ 53.2±11.7 22.0±1.21
ΔΔ 0.80±0.29
ΔD 0.50±0.07
ΔΔ 65.0±5.01
*ΔΔ# 79.9±16.8
Δ 64.6±8.77
** 22.6±1.92
ΔΔ 0.56±0.13
*Δ
#P＜0.05 vs group C2.3 glycyrrhizic acid is to CCl
4The mouse liver pathological change the perusal A group mouse liver that influences be bronzing, smooth surface, matter is soft; B organizes obvious swelling, dark-yellow complexion, and matter is hard; The enlargement slightly of C group part liver is yellowish-brown, and the surface is still smooth; The D group is similar to the C group substantially.The HE structure normal (seeing A) under the visible A arrangement of mirrors that dyes, the normal configuration of B group liver is destroyed, the lobules of liver arrangement disorder, the large stretch of degeneration of hepatocyte, necrosis, be the bridge joint shape, the a large amount of lymphocytic infiltrations in portal area, central vein off normal or scarce as (seeing B), relatively there were significant differences (P＜0.001) with the A group.Visible hepatic tissue structure is more complete under the C arrangement of mirrors, and hepatocellular degeneration, downright bad situation be light (seeing C), and relatively there were significant differences (P＜0.01) with the B group, and D mice pathological changes is obviously light than the B group, structure and C winding nearly (P＞0.05) (seeing D) under the mirror; The VG visible A group liver that dyes does not have proliferation of fibrous tissue (seeing A-1), in B group hepatic tissue portal area and the liver parenchyma more collagen fiber hypertrophy is arranged, in liver parenchyma, extend and hold, cut apart liver parenchyma, the fibrosis rate reaches 100%, (seeing B-1), the collagen fiber hyperplasia degree of C group murine liver tissue is than B group light (seeing C-1), has remarkable meaning (P＜0.01) with the difference of B group, visible small amount of fibers tissue around D organizes only in the portal area, do not extend in liver parenchyma, hyperplasia degree is obviously than B group light (P＜0.01) (seeing D-1).Each is organized murine liver tissue HE dyeing light microscopic following table and now sees Table 3, and VG dyeing liver tissue fibrosis degree sees Table 4.
Table 3: glycyrrhizic acid is to CCl
4Under the murine liver tissue HE dyeing light microscopic pathology of livers influence
(n＝10)
Group Degeneration Necrosis
- + ++ +++ - + ++ +++
A 9 1 0 0 10 0 0 0
B 0 0 0 8 0 0 1 7
C 0 0 4 6 0 0 7 3
D 0 0 5 5 0 2 6 2group?B?vs?group?A，P＜0.001，group?B?vs?group?C?and?vs?groupb?D，P＜0.01，groupb?D?vs?group?C，P＞0.05.
Table 3: glycyrrhizic acid is to CCl
4The influence of murine liver tissue VG dyeing liver tissue fibrosis pathological change
(n＝10)
Group Collagenous Fiber
- + ++ +++
A 10 0 0 0
B 0 0 1 7
C 0 0 7 3
D 008 2group B vs group A, P＜0.001, group B vs group C and vs groupb D, P＜0.01, groupb D vs group C, P＞0.05.2.4 glycyrrhizic acid is to CCl
4The influence of mice sclerotin as seen from Table 5, the right femoral shaft anharmonic ratio A group of B group alleviates (P＜0.05), the content of bone calcium and bone hydroxyproline significantly descend (P＜0.01); Unit bone calcium (calcium amount/bone is heavy) changes little and unit bone hydroxyproline decline (P＜0.01).The calcium content of bone that C, D are two groups is lower than A group (P＜0.05), but than B group high (P＜0.05), and bone hydroxyproline content and A group there was no significant difference (P＞0.05); D group backbone is heavy gently and than the C group to weigh (P＜0.05) unlike the A group, illustrates that glycyrrhizic acid is to CCl
4Contamination mice bone loss has preferable preventive and therapeutic effect; B group unit bone calcium is few unlike the A group, and the prompting chronic hepatic injury causes bone loss to lose based on the organic matter of bone.
Table 5: glycyrrhizic acid is to CCl
4The influence of the content of mice bone weight, bone calcium, bone bone hydroxyproline
(X ± S, n=10) Group BW (mg) Ca
2+(mg) Ca
2+Heavy (mg/g) A 51.2 ± 8.42 4.06 ± 0.54 80.8 ± 14.8 2.7 ± 0.72 54.2 ± 17.9 B 37.2 ± 7.04 of heavy (mg/g) Hyp (mg) Hyp/ of/bone bone
*2.70 ± 0.51
*73.1 ± 10.5 0.80 ± 0.43
*22.5 ± 13.2
*C 47.1 ± 2.80
*3.36 ± 0.20
*71.3 ± 3.2 2.25 ± 0.48
The Δ Δ48.3 ± 11.7
ΔD 51.1 ± 7.44
Δ Δ #3.32 ± 0.37
*65.6 ± 5.5
*3.5 ± 0.81
The Δ Δ69.1 ± 16.5
The Δ Δ2.5 glycyrrhizic acid is to CCl
4The B that influences of mice bone micronutrient levels organizes the heavy Cu of right femur unit bone
2+, Mg
2+And Zn
2+Content all than A group high (P＜0.01), C organize also high (P＜0.05), and the content of D group is organized there was no significant difference (P＞0.05) with A, but organize than B low, (P＜0.05); The bone Fe of unit of B, C, three groups of right femurs of D
2+Content all reduce than A group, but do not have significance (P＞0.05), and the B class value is higher, considers relevant with the heavy obviously minimizing of bone of B group.Table 6 shows that glycyrrhizic acid can effectively prevent copper, zinc, magnesium accumulating in vivo, but can not increase CCl
4Iron content in the contamination mouse unit bone.
Table 6: glycyrrhizic acid is to CCl
4The influence of mice bone micronutrient levels (X ± S, n=10) Group Cu
2+(mg/g) Zn
2+(mg/g) Mg
2+(mg/g) Fe
2+(mg/g) A 1.02 ± 0.36 2.23 ± 1.51 6.00 ± 0.96 0.90 ± 0.56 B 1.99 ± 0.59
*4.46 ± 2.15
*9.07 ± 2.57
*0.80 ± 0.66 C 1.27 ± 0.38
* Δ4.35 ± 3.60
*6.34 ± 1.73
*0.73 ± 0.49 D 1.11 ± 0.24
Δ2.41 ± 0.98
Δ5.82 ± 0.99
Δ0.74 ± 0.243 discusses
To white mice row subcutaneous injection, 5 days once, five weeks of logotype with 40% carbon tetrachloride Oleum Arachidis hypogaeae semen in this experiment.The result shows that B group mice serum transaminase obviously increases, and albumin significantly descends, and the hepatic pathology section shows typical hepatic fibrosis performance, is successful so this experiment causes the experimental animal model of hepatic injury heptic fibrosis with carbon tetrachloride contamination mice.
In the Liver Fibrosis Model due to the liver chronic injury, we have found that the bone loss of mice is obvious, in this experiment, right femur dry weight, the Ca of B group mice
2+Total amount significantly descends, the content of hydroxyproline also obviously descends in the bone, the organic matter and the inanimate matter of the minimizing of bone representation work, bone are all obviously lost after the prompting hepatic injury, notice that mice is in bone loss, serum albumin significantly descends, consider this bone loss may with liver synthetic proteins obstacle, cause some to promote the synthetic factor of bone to reduce relevant.The content that bone copper, bone magnesium, the bone zinc of hepatic injury mice are observed in this research simultaneously has increase in various degree.Copper is the cofactor of lysyloxidase in the bone matrix, and this enzyme has the function that promotes the ossein intramolecular crosslinking to form, stablize collagen structure
[11], document was once reported the excessive renal damage that causes of copper and is caused bone calcium to be lost in a large number, and can form osteoporosis
[12], also have report copper to reduce the conversion ratio of bone by being suppressed to the function of osteocyte and osteoclast
[13], excessive copper can cause osteoblast and mesenchymal grievous injury and cause the atrophy of osseous tissue
[14], infer hepatic injury in view of the above after the mice bone loss may be relevant with the increase of bone copper.The effect of magnesium and bone metabolism is also very close, has the oral magnesia mixture of report can suppress adult bone conversion
[15], also there is the reported literature magnesium deficiency to cause osteoporosis by the activity that increases osteoclast, its mechanism is unclear
[16], we consider that this may to stop noncrystalline calcium phosphate to be transformed into hydroxyapatite relevant with magnesium.The influence to bone metabolism of increasing in chronic hepatopathy of bone copper and bone magnesium is one and is worth the problem deeply inquired into.
Colchicine is the medicine of the anti-hepatic fibrosis of classics, studies show that, after the white mice of carbon tetrachloride contamination gavages Colchicum autumnale simultaneously, weight increase 17%, the content of the glutamate pyruvate transaminase of mice serum has significantly descended 32%, serum albumin levels has increased by 42%, A/G ratio increases 87%, sick inspection also proves the liver cell degeneration, downright bad and degree of hepatic fibrosis all has obviously and alleviates, pointed out Colchicum autumnale that hepatic fibrosis is had certain preventive effect, on the other hand, the bone calcium of C group and bone hydroxyl proline have increase to a certain degree, bone copper also descends (P＜0.05), and this may be relevant with the colchicine the liver protecting and ALT lowering.
Glycyrrhiza leguminous plant (Glycyrrhiza Ura Lensis Fisch), but heat reliving and toxin-eliminating, the toxicity of cushion and strong.Glycyrrhizic acid (glycyrrhinic acid C
42H
6O
16) be the effective ingredient of Radix Glycyrrhizae, but the generation of existing bibliographical information glycyrrhizic acid strong inhibition free radical and lipid peroxide and inhibition Ca
2+Interior stream causes hepatocellular damage
[17]Glycyrrhizic acid 100mg.kg is found in this experiment
-1Irritate stomach and can make serum glutamic pyruvic transminase decline 41%, the plasma albumin of carbon tetrachloride contamination white mice raise 32%, the A/G value also significantly improves, and we have also affirmed the effect of its anti-hepatic fibrosis from the liver pathology angle; On the other hand, carbon tetrachloride causes chronic hepatic injury that mouse femur bone calcium total amount and bone hydroxyproline content are reduced simultaneously, especially with bone hydroxyproline obvious (bone calcium total amount descends 34%, and the bone hydroxyproline content descends 70%, P＜0.01).The bone hydroxyproline is mainly synthesized and secretion by osteoblast, and therefore, carbon tetrachloride may be to make its synthetic and secretion ossein minimizing by being suppressed to osteocyte, thereby reduces calcareous deposition
[18]And cause bone loss.Bone calcium is the important component that constitutes bone mineral, and the bone hydroxyproline is the distinctive aminoacid of ossein, and its minimizing is the outstanding feature that bone matrix reduces.And glycyrrhizic acid is irritated the weight increase 16% (P＜0.05 ') that can make the carbon tetrachloride mice behind the stomach, bone heavily increases by 37% (P＜0.01), bone calcium increases by 23%, the bone hydroxyproline increases more than 3 times, illustrate that glycyrrhizic acid can obviously promote osteoblastic growth and strengthen its secretory function, thereby prevent losing of bone loss; In addition; we find that also glycyrrhizic acid can make the content of the unit bone copper of mouse femur and bone magnesium 44% and 36% (P＜0.05) that descended respectively; so 1. the mechanism of action of considering the bone loss due to the glycyrrhizic acid control hepatic fibrosis may be by inducing liver drug enzyme; strengthen the liver detoxification effect; quicken the drainage and the metabolism of poisonous substance; 2. the liver protecting is kept the Proteometabolism level.3. keep the normal metabolism of bone, promote the balance of bone calcium and bone hydroxyproline and bone trace element, 4. promote osteoblastic function, the effect that increases synthetic this four aspect of bone realizes.
List of references 1 Tiegs G, Experimental hepatitis and role of cytokines. ActaGastroenterol-Belg, 1997Gastroenterol60 (2): 176-92 " national Chinese herbal medicine compilation " writes group." national Chinese herbal medicine compilation " first volume.Beijing: People's Health Publisher, 1986:237-2393 Vleggaar FP, van Buuren HR, Wolfhagen FH, et al. Prevention andtreatment of osteoporosis in primary biliary cirrhosis. Eur JGastroenterol Hepatol, 1999,11 (6): 617-214 Gonzalez Sanz-Agero P, Munoz Nunez F, Erdozain Sosa JC, et al.Bone metabolism in non-cholestatic chronic hepatopathy. Med Clin (Barc) 1998, CL (12): 446-505 Olsson R, Mattsson LA, Obrant K, et al.Estrogen-progestogentherapy for low bone mineral density in primary biliary cirrhosis.Liver, 1999,19 (3): 188-926 Shiomi S, Masaki K, Habu D, et al.Calcitriol for bone disease inpatients with cirrhosis of the liver.J Gastroenterol Hepatol, 1999,14 (6): 547-527 opens the chief editor that divides field equally. the modern pharmacology experimental technique. and Beijing: combined publication society of China Concord Medical Science University of Beijing Medical University, 1998:13998 Wang Xiayi chief editor. the clinical biochemical inspection technology. Nanjing: publishing house of Nanjing University, 1995:180-182; 185-188; 279-284 9 poplar Yulins, the He Zhian chief editor. the hepatic disease laboratory diagnosis. Beijing: Chinese Medicine science and technology publishing house, 1996:3bb10 Wu Zhongbi chief editor. pathology. Beijing: People's Health Publisher, 1996:289-9211 Yee CD, Kubena KS, Walker M, et al.The relationship ofnutritional copper to the deve lopment of postmenopausal osteoporosisin rats. Biol Trace Elem Res, 1995,48 (1): 1-1112 Walshe JM. Copper:not too little, not too much, but just right.London:J R Coll Physicians Land, 1995.29 (4): 280-813 Okano T. Effects of essentiai trace elements on bone turnoverin relation to the osteoporosis. Nippon Rinsho, 1996,54 (1): 148-5414 Kozuka H. Interactive exhibition of heavy metal toxicity in bonemetabolism from the viewpoint of deductive toxicology. YakugakuZasshi 1995,115 (3): 157-6915 Dimai HP, Porta S, Wirnsberger G, et al.Daily oral magnesiumsupplementation suppresses bone turnover in young adult males.J ClinEndocrinol Metab 1998,83 (8): 2742-816 Rude RK, Kirchen ME, Gruber HE, et al.Magnesiumdeficiency-induced osteoporosis in the rat:uncoupling of boneformation and bone resumption. Magnes Res 1999,12 (4): the cloudy strong chief editor of 257-6717. " Chinese medicine modern study and clinical practice ". Beijing: Xueyuan Press 1993:196-20318 Liu Zhonghou chief editor. osteoporosis. Beijing: Science Press, 1998:32
Embodiment two
According to above experimental result, we adopt glycyrrhizic acid and calcium preparation to form compound preparation, set up the osteoporosis animal model with cyclophosphamide, observe glycyrrhizic acid and calcium preparation composition compound preparation and prevented and treated osteoporotic effect, the result proves that glycyrrhizic acid and calcium preparation composition compound preparation have the osteoporotic effect of good control, wherein, it is best that glycyrrhizic acid and calcium gluconate are formed the compound preparation effect.Glycyrrhizic acid 5mg/kg, the dosage range of 50 mg/kg and 100mg/kg, calcium gluconate 0.1g/kg, 0.5g/kg and 1g/kg dosage range are formed compound recipe effect stability, good effect.
Embodiment three
According to above experimental result, we adopt Radix Glycyrrhizae or glycyrrhizic acid by traditional preparation process, make the novel formulation that is used for osteoporosis disease, as tablet, electuary, capsule, injection or oral liquid, be used for clinical osteoporotic control, obtain clinical effectiveness preferably.Extract triterpenoid compound glycyrrhizin of the dry root of Radix Glycyrrhizae (glycyrrhizin glycyrrhizin or glycyrrhizic acid glycyrrhizicacid) and enoxolone (glycyrrhetinic acid), flavone compound liquiritin (liquiritin or title liquiritin), isoliquiritin (isoliquiritin), glycyrrhizin (liquiriligenin), isoliquiritigenin (iso-liquiriligenin) and Angelica Polysaccharide also can be made the novel formulation that is used for osteoporosis disease separately, as tablet, electuary, capsule, injection or oral liquid are used for clinical osteoporotic control.The said extracted thing of Radix Glycyrrhizae and Radix Glycyrrhizae also can be formed compound recipe with calcium gluconate or other calcium preparation compositions, is used for protect against osteoporosis.
Claims (9)
1, Radix Glycyrrhizae and Radix Glycyrrhizae extract are used for the application of the preparation of protect against osteoporosis in preparation.
2, the Radix Glycyrrhizae extract glycyrrhizic acid is used for the application of the preparation of protect against osteoporosis in preparation.
3, Radix Glycyrrhizae extract liquiritin, isoliquiritin are used for the application of the preparation of protect against osteoporosis in preparation.
4, the Radix Glycyrrhizae extract Angelica Polysaccharide is used for the application of the preparation of protect against osteoporosis in preparation.
5, Radix Glycyrrhizae extract glycyrrhizin, isoliquiritigenin are used for the application of the preparation of protect against osteoporosis in preparation.
6, the Radix Glycyrrhizae extract enoxolone is used for the application of the preparation of protect against osteoporosis in preparation.
7, the compound preparation of Radix Glycyrrhizae extract glycyrrhizic acid and calcium preparation composition is used for the application of the preparation of protect against osteoporosis in preparation.
The compound preparation that 8 Radix Glycyrrhizae extract glycyrrhizic acids and calcium gluconate are formed is used for the application of the preparation of protect against osteoporosis in preparation.
9,, it is characterized in that this composition contains the extract triterpenoid compound glycyrrhizin of the dry root of Radix Glycyrrhizae (glycyrrhizin glycyrrhizin or glycyrrhizic acid glycyrrhizic acid) and enoxolone (glycyrrhetinic acid), flavone compound liquiritin (liquiritin or title liquiritin), isoliquiritin (isoliquiritin), glycyrrhizin (liquiriligenin), isoliquiritigenin (iso-liquiriligenin) and Angelica Polysaccharide as claims 1 described Radix Glycyrrhizae extract.
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| CN 02108186 CN1446549A (en) | 2002-03-25 | 2002-03-25 | Use of licorice and its extract for treating osteoporosis |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 02108186 CN1446549A (en) | 2002-03-25 | 2002-03-25 | Use of licorice and its extract for treating osteoporosis |
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| CN1446549A true CN1446549A (en) | 2003-10-08 |
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| CN 02108186 Pending CN1446549A (en) | 2002-03-25 | 2002-03-25 | Use of licorice and its extract for treating osteoporosis |
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| WO2008007214A2 (en) * | 2006-07-07 | 2008-01-17 | Avestha Gengraine Technologies Pvt. Ltd. | Glycyrrhiza glabra plant extracts for treating osteoporosis and the extraction process thereof |
| WO2008051586A3 (en) * | 2006-10-24 | 2008-09-25 | David W Krempin | Anti-resorptive and bone building dietary supplements and methods of use |
| US7897184B1 (en) | 2009-08-13 | 2011-03-01 | Access Business Group International Llc | Topical composition with skin lightening effect |
| CN101525391B (en) * | 2009-03-31 | 2011-05-11 | 武汉大学 | Method for extracting amylase from liquorice and application thereof |
| CN102367424A (en) * | 2011-09-30 | 2012-03-07 | 河北农业大学 | Coriobacterium sp. AUH-Julong21 and use of coriobacterium sp. AUH-Julong21 in liquiritigenin conversion |
| CN104189553A (en) * | 2014-07-26 | 2014-12-10 | 广东医学院 | Application of composition containing coenzyme Q10 and vegetable oil to preparation of health foods and medicines for preventing osteoporosis |
| CN108578470A (en) * | 2018-05-23 | 2018-09-28 | 广东永青生物科技有限公司 | The pharmaceutical composition that the hyperthyroid high conversion hysteria bone loss of one group of improvement and bone biomechanical property decline |
| CN114848659A (en) * | 2022-06-14 | 2022-08-05 | 广州医科大学附属口腔医院（广州医科大学羊城医院） | Application of isoliquiritin in preparation of medicine for treating osteoporosis |
| CN115089694A (en) * | 2022-07-25 | 2022-09-23 | 中国中医科学院中医基础理论研究所 | Liquorice protein extract and new application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2008007214A3 (en) * | 2006-07-07 | 2009-04-30 | Avestha Gengraine Tech Pvt Ltd | Glycyrrhiza glabra plant extracts for treating osteoporosis and the extraction process thereof |
| WO2008007214A2 (en) * | 2006-07-07 | 2008-01-17 | Avestha Gengraine Technologies Pvt. Ltd. | Glycyrrhiza glabra plant extracts for treating osteoporosis and the extraction process thereof |
| US9446087B2 (en) | 2006-10-24 | 2016-09-20 | David W. Krempin | Anti-resorptive and bone building dietary supplements and methods of use |
| WO2008051586A3 (en) * | 2006-10-24 | 2008-09-25 | David W Krempin | Anti-resorptive and bone building dietary supplements and methods of use |
| WO2008051594A3 (en) * | 2006-10-24 | 2008-10-09 | David W Krempin | Anti-resorptive and bone building dietary supplements and methods of use |
| EP2415469A1 (en) * | 2006-10-24 | 2012-02-08 | David W. Krempin | Anti-Resorptive and Bone Building Dietary Supplements and Methods of Use |
| US11207368B2 (en) | 2006-10-24 | 2021-12-28 | Murray Mary A | Anti-resorptive and bone building dietary supplements and methods of use |
| CN101525391B (en) * | 2009-03-31 | 2011-05-11 | 武汉大学 | Method for extracting amylase from liquorice and application thereof |
| US7897184B1 (en) | 2009-08-13 | 2011-03-01 | Access Business Group International Llc | Topical composition with skin lightening effect |
| US8202556B2 (en) | 2009-08-13 | 2012-06-19 | Access Business Group International Llc | Topical composition with skin lightening effect |
| CN102367424A (en) * | 2011-09-30 | 2012-03-07 | 河北农业大学 | Coriobacterium sp. AUH-Julong21 and use of coriobacterium sp. AUH-Julong21 in liquiritigenin conversion |
| CN104189553A (en) * | 2014-07-26 | 2014-12-10 | 广东医学院 | Application of composition containing coenzyme Q10 and vegetable oil to preparation of health foods and medicines for preventing osteoporosis |
| CN108578470A (en) * | 2018-05-23 | 2018-09-28 | 广东永青生物科技有限公司 | The pharmaceutical composition that the hyperthyroid high conversion hysteria bone loss of one group of improvement and bone biomechanical property decline |
| CN114848659A (en) * | 2022-06-14 | 2022-08-05 | 广州医科大学附属口腔医院（广州医科大学羊城医院） | Application of isoliquiritin in preparation of medicine for treating osteoporosis |
| CN115089694A (en) * | 2022-07-25 | 2022-09-23 | 中国中医科学院中医基础理论研究所 | Liquorice protein extract and new application thereof |
| CN115089694B (en) * | 2022-07-25 | 2023-08-18 | 中国中医科学院中医基础理论研究所 | Glycyrrhiza protein extract and new application thereof |
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