CN107184645A - It is a kind of to treat compound Chinese medicinal preparation of osteoporotic fracture and its production and use - Google Patents
It is a kind of to treat compound Chinese medicinal preparation of osteoporotic fracture and its production and use Download PDFInfo
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Abstract
The invention discloses a kind of compound Chinese medicinal preparation for treating osteoporotic fracture, it is prepared from by strengthening spleen, tonifying kidney Chinese medicine and excipient substance, the composition and its parts by weight of the strengthening spleen, tonifying kidney Chinese medicine are：Radix Codonopsis 6 30, wilsonii 6 30, the rhizome of davallia 6 30, barrenwort 6 30, the red sage root 6 15, levisticum 3 12.Jianpi Bushen of the present invention is theoretical based on " spleen kidney is related ", " first the foundation of acquired constitution ", found through zoopery, strengthening spleen, tonifying kidney can remarkably promote healing of the osteoporotic fracture mouse in different times poroma after removal ovary, improve the bone amount and bone biomechanical intensity of poroma, promote the expression of β-catenin in fracture site muscle and poroma, increase the quantity of Muscle-derived Stem Cells and its proliferation activity of promotion in fracture site muscle, and promote Muscle-derived Stem Cells to migrate to poroma, so as to stimulate Osteoblast Differentiation, accelerate union of osteoportic fracture.Invention additionally discloses the preparation method of the compound Chinese medicinal preparation and medical usage.
Description
Technical field
The present invention relates to a kind of compound Chinese medicinal preparation for treating osteoporotic fracture, moreover, it relates in this
The preparation method and medical usage of medicine compound preparation.
Background technology
Osteoporotic fracture is the severe complication of osteoporosis, often can cause whole body under the effect of slight external force
Each position fracture, is mainly in backbone, hip and radioulna distal end, and other positions are also easily fractured, and can often cause fracture site
Pain, deformity, dysfunction, spine fracture can also cause height to become short, bow-backed etc..
With China human mortality aging, obvious ascendant trend is also presented in the primary osteoporosis incidence of disease, causes
Osteoporotic fracture is also more and more.For the treatment of osteoporotic fracture, No operation and operative treatment are broadly divided into, but
Because patients with osteoporosis itself Gegenbaur's cell joins unbalance, the time delay of its union of relation with osteoclast lotus root,
Even disunion, also more normal person is poor for prognosis quality, be easily caused again perform the operation or secondary fracture risk, to patient's body, spirit,
Heavy burden is carried out in economy-zone.Therefore, also need to combine systematicness management, anti-osteoporosis treatment (Western medicine, Chinese medicine, physical therapy, health
Refreshment white silk, kinesiatrics).
Traditional Chinese medicine plays an important roll and exclusive characteristic in terms of anti-curing osteoporosis.But due to osteoporotic fracture
The elderly is mainly in, the cardinal principle of non-operative treatment is long-term fixed braking, adds somewhat to bedsore, Deep venou
The risk of the complication such as thrombus, pulmonary infection and cardiovascular and cerebrovascular diseases, its harmfulness has been even more than fracture in itself.Therefore with regard to sclerotin
For the preferred therapy of osteoporotic fractures, traditional Chinese medicine is relative to modem surgical treatment just without so obvious advantage.But, bone
The incidence of matter osteoporotic fractures second fracture is of a relatively high, it is necessary to adhere to that anti-osteoporosis is treated, Western medicine, Chinese medicine can conducts
Main supplementary means.Although operation can solve the reset, fixation and early rehabilitation exercise of fracture site, due to Old Men
Factor is weaker, underlying diseases are more, still has the generation of fracture delayed union and disunion, by the anti symptom treatment of traditional Chinese medicine and
It is integrally-regulated, the special advantage of traditional Chinese medicine can be given full play to.
Syndrome of yang deficiency of spleen and kidney is one of important card type of primary osteoporosis fracture, and therefore, the present invention selects Shi Qijiao
Award the Empirical formula faced in examining --- Jianpi Bushen, by the inside and outside experiment of body, studied, tied with modern science means
Conjunction-elder generation's the foundation of acquired constitution " ,-spleen kidney are related " theory of traditional Chinese medical science, promote union of osteoportic fracture to illustrate Jianpi Bushen
Mechanism of action and efficacy analysis, and then certain theoretical direction is provided for clinician when in diagnosis and treatment, this is sick.
The content of the invention
For the above-mentioned deficiency of prior art, embodiments in accordance with the present invention, it is desirable to propose a kind of determined curative effect, security
Compound Chinese medicinal preparation --- the Jianpi Bushen of high treatment osteoporotic fracture, and propose its preparation method and pharmaceutical
On the way.
Chinese medicinal material quality involved in the present invention all should meet each under the corresponding medicinal material of Chinese Pharmacopoeia version one in 2015
Pertinent regulations.Wherein：
Radix Codonopsis is Campanulaceae Radix Codonopsis Codonopsispilosula (Franch.) Nannf., codonopsis pilosula var. modesta
CodonopsispilosulaNannf.var.modesta (Nannf.) L.T.Shen or radix codonpsis tangshen
CodonopsistangshenOliv. dry root.
Wilsonii is Araliaceae wilsonii Acanthopanax senticosus (Rupr.et Maxim.) Harms
Drying root and rhizome or stem.
The rhizome of davallia is Plants of Polypodiaceae Mongolian oak fern Drynariafortunei (Kunze) J.Sm. dry rhizome.
Barrenwort is Berberidaceae plant barrenwort EpimediumbrevicornuMaxim dried leaf.
Dry root and rhizome that the red sage root is labiate red sage root SalviamiltiorrhizaBge..
Levisticum is samphire Angelica pubescens Angelica pubescens Maxim.f.biserrata Shan
Et Yuan dry root.
Specifically, the present invention treatment osteoporotic fracture compound Chinese medicinal preparation, by above-mentioned strengthening spleen, tonifying kidney Chinese medicine with
Excipient substance is made, and the weight of the strengthening spleen, tonifying kidney Chinese medicine is as follows：Radix Codonopsis 6-30, wilsonii 6-30, rhizome of davallia 6-30,
Barrenwort 6-30, red sage root 6-15, levisticum 3-12.
The strengthening spleen, tonifying kidney Chinese medicine of compound Chinese medicinal preparation of the present invention is by ethanol or aqueous solvent is extracted and alcohol precipitation, the method for filtration
Purifying, the extracting method employed in it is the physicochemical property according to active ingredient in medicine, and the extraction from alcohol precipitation, filtration is molten
Agent and extraction conditions；The purification process used is on the premise of curative effect is ensured, from ethanol precipitation through row purification process.
The invention provides the preparation method of above-mentioned compound Chinese medicinal preparation.
Compound Chinese medicinal preparation of the present invention is prepared by following method and steps：
1. weigh each medicinal material by prescription weight, soak 1h, decoct 1~3 time, decoct 0.5~1.5h every time, one decocts and adds water 10
~14 times, two, three decoct 6~10 times of amount of water, merge decoction liquor, filter, at a temperature of 60~70 DEG C, filtrate is concentrated into relatively close
Spend the medicinal extract for 1.05~1.30.Wherein, preferably decoct 2 times, decoct 1h every time, one decocts and adds water 14 times, and two decoct 10 times of amount of water,
Merge decoction liquor, filtration, preferably filtered solution are concentrated into the medicinal extract liquid that relative density is 1.05~1.07；
2. add ethanol in above-mentioned 1. medicinal extract liquid, to concentration of alcohol be 50%~80%, preferably plus ethanol to concentration be
60%；Stand overnight, alcohol precipitation.Filtration, filtrate reclaims ethanol at a temperature of 60~70 DEG C, and be concentrated into relative density for 1.35~
1.40 equivalent extract；
3. above-mentioned 2. equivalent extract is dried under reduced pressure at 70~80 DEG C, is ground into fine powder, is crossed 60 mesh sieves, is produced extract powder；
4. according to extract powder：Filler：Disintegrant=12：5：1 part by weight proportioning (extract powder, MCC,
Cross-linked carboxymethyl cellulose is received), above-mentioned 3. obtained component is taken, filler, the disintegrant of aforementioned proportion is added.Mix, use
Dry granulation, tabletted, film coating, is made finished tablet, produces.
The preparation method of compound Chinese medicinal preparation of the present invention, employs water extraction method and preferred decoction number of times, time and adds
Water, and the density and concentration of alcohol of preferred alcohol precipitation purifies through row alcohol precipitation, effective component extracting and goes removal of impurities to greatest extent
Matter, concentrates under decompression cryogenic conditions, dries, while to drying means and condition, the auxiliary material of preparations shaping technique, method of granulating
And condition etc. preferably goes out through row examination, screening and is suitable for industrialized preparation technology.
Compound Chinese medicinal preparation of the present invention can be made various oral formulations according to a conventional method, including tablet, granule, capsule,
Mixture, powder etc..
Jianpi Bushen of the present invention is by finding that invigorating the spleen is mended in the medical application for the treatment of osteoporotic fracture
Kidney side is drawn to the effect curative effect of osteoporotic fracture animal model.
Zoopery finds, Jianpi Bushen can remarkably promote after removal ovary osteoporotic fracture mouse when different
The healing of phase poroma, be included in fracture 0-7 days early stage can promote visible a large amount of fertilizer near intramembranous ossification and entochondrostosis, the broken ends of fractured bone
Big the proliferation of chondrocytes；And in the fracture middle and later periods, 14-28 days, articular chondrocyte apoptosis promoted a large amount of hyperplasia of Gegenbaur's cell, together
When, amount of osteoclast will not be suppressed, to play a part of the moulding reconstruction of poroma, ossis is led to again.Strengthening spleen, tonifying kidney can be bright
The aobvious bone amount and bone strength for improving poroma.Jianpi Bushen promotes the expression of β-catenin in fracture site muscle and poroma.It is strong
Its increment of the quantity and promotion of Muscle-derived Stem Cells in spleen Bushen Prescription increase fracture site muscle.Jianpi Bushen promotes muscle-derived
Stem cell migration is to poroma, so as to stimulate skeletonization, accelerates union of osteoportic fracture.
When Jianpi Bushen of the present invention is used to treat osteoporotic fracture, with Chinese herbs decoction, agriculture we, particle
The forms such as agent are used.
Brief description of the drawings
In the following drawings：Saline-physiological saline；JPBS- strengthening spleen, tonifying kidneys；QGJN- QIANGGU JIAONANGs.Diaphysis fraction
(BV/TV), bone trabecula number (Tb.N), bone trabecula thickness (Tb.TH), bone trabecula separating degree (Tb.Sp), bone density (mean/
density of TV、mean/density of BV)。
Fig. 1 be removal ovary after March model group with sham-operation group serum estradiol comparision contents.
Fig. 2 be physiological saline, Jianpi Bushen and QIANGGU JIAONANG each group intervene osteoporotic fracture after 28 days serum it is female
Glycol content compares.
Fig. 3 Ovariectomy models group and sham-operation group lumbar vertebrae Micro-CT three-dimensional reconstructions.
Fig. 4 Ovariectomy models group and sham-operation group lumbar vertebrae Micro-CT parameter situations.
Fig. 5 is Ovariectomy model group and sham-operation group shin bone Micro-CT parameter situations.
Fig. 6 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene mouse 7,14,28 days fracture site X-Ray lines.
Fig. 7 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene mouse 7,14,28 days poroma three-dimensional reconstructions.
Fig. 8 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene mouse 7,14,28 days shin bone poroma Micro-CT ginsengs
Number situation.
Fig. 9 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene the ossa tibiale posterius fracture site biomethanics of mouse 28.
Figure 10 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene union position force analysis after mouse 28.
Figure 11 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene mouse 7,14,28 days fracture of tibia position HE dyes
Color.
Figure 12 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene mouse 7,14,28 days fracture of tibia position ABH/
OG is dyed.
Figure 13 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene mouse 7,14,28 days fracture of tibia position TRAP
Dyeing.
Figure 14 be physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene mouse 7,14,28 days fracture of tibia position β-
Catenin is dyed.
Figure 15 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene mouse 7,14,28 days fracture of tibia component R unx2
Dyeing.
Figure 16 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene 7 days gastrocnemius Pax7+BrdU immunofluorescences of mouse
Dyeing.
Figure 17 be physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene 14 days gastrocnemius Pax7+BrdU of mouse be immunized it is glimmering
Light is dyed.
Figure 18 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene 7 days gastrocnemius MyoD+BrdU immunofluorescences of mouse
Dyeing.
Figure 19 be physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene 14 days gastrocnemius MyoD+BrdU of mouse be immunized it is glimmering
Light.
Figure 20 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene 7 days tibialis posterior correlating markings gene tables of mouse
Reach.
Figure 21 is that physiological saline, Jianpi Bushen and QIANGGU JIAONANG intervene 14 days tibialis posterior correlating markings gene tables of mouse
Reach.
Embodiment
Below in conjunction with the accompanying drawings and specific embodiment, the present invention is expanded on further.These embodiments are interpreted as being only used for
It is bright the present invention rather than limit the scope of the invention.After the content of the invention recorded has been read, art technology
Personnel can make various changes or modifications to the present invention, and these equivalence changes and modification equally fall into the claims in the present invention and limited
Fixed scope.
Bulk drug is weighed according to weight, 1h is soaked, decocted 1~3 time, 0.5~1.5h is decocted every time, and one decocts and adds water
10~14 times, two, three decoct 6~10 times of amount of water, merge decoction liquor, filter, at a temperature of 60~70 DEG C, filtrate is concentrated into relatively
Density is 1.05~1.30 medicinal extract；
2. ethanol is added in above-mentioned 1. medicinal extract liquid, is 50%~80% to concentration of alcohol, stands overnight, alcohol precipitation.Filtration, filter
Liquid reclaims ethanol at a temperature of 60~70 DEG C, and is concentrated into the equivalent extract that relative density is 1.35~1.40；
3. above-mentioned 2. equivalent extract is dried under reduced pressure at 70~80 DEG C, is ground into fine powder, is crossed 60 mesh sieves, is obtained the leaching of drug component
Cream powder；
4. according to：Extract powder：Filler：Disintegrant=12：5：1 part by weight proportioning (extract powder, MCC,
Cross-linked carboxymethyl cellulose is received), above-mentioned 3. worth component is taken, filler, the disintegrant of aforementioned proportion is added.Mix, use
Dry granulation, tabletted, film coating, is made finished tablet, produces.Or various oral formulations are made according to a conventional method, wrap
Include tablet, granule, capsule, mixture, powder etc..
Embodiment 1
Bulk drug weight proportion：Radix Codonopsis 6g, wilsonii 6g, rhizome of davallia 6g, barrenwort 6g, red sage root 6g, levisticum 3g.
Embodiment 2
Bulk drug weight proportion：Radix Codonopsis 30g, wilsonii 30g, rhizome of davallia 30g, barrenwort 30g, red sage root 15g, levisticum 12g.
Embodiment 3
Bulk drug weight proportion：Radix Codonopsis 5.5g, wilsonii 5.5g, rhizome of davallia 5.5g, barrenwort 5.5g, red sage root 4.5g, solely
3g living.
Embodiment 4
Bulk drug weight proportion：Radix Codonopsis 15g, wilsonii 15g, rhizome of davallia 15g, barrenwort 15g, red sage root 12g, levisticum 9g.
Embodiment 5
Bulk drug weight proportion：Radix Codonopsis 5g, wilsonii 5g, rhizome of davallia 5g, barrenwort 5g, red sage root 4g, levisticum 3g.
Embodiment 6
Bulk drug weight proportion：Radix Codonopsis 12g, wilsonii 12g, rhizome of davallia 12g, barrenwort 12g, red sage root 9g, levisticum 6g.
Embodiment 7
Bulk drug weight proportion：Radix Codonopsis 12g, wilsonii 12g, rhizome of davallia 9g, barrenwort 9g, red sage root 12g, levisticum 9g.
Test example
Effect study of the Jianpi Bushen to removal ovary osteoporotic fracture mouse.
1 materials and methods
1.1 experimental animal
Female 55 of 2 monthly age C57BL/6 are ordered by Shanghai Univ. of Traditional Chinese Medicine's Animal House, SPF grades were raised to 3 monthly ages.It is all dynamic
Thing equal free water and feed in whole experiment process.Credit number：SCXK (capital) 2012-0001.
1.2 Experimental agents
Jianpi Bushen：It is made, is randomly selected by embodiment 1-7；QIANGGU JIAONANG (Beijing Qihuang Pharmaceutical Co., Ltd) by
Longhua hospital provides；10% chloraldurate parenteral solution, lot number：20081027, Chemical Reagent Co., Ltd., Sinopharm Group；Ultra-
The super quick estradiol kits of Sensitive Estradiol RIA (Beckman Coulter, DSL-4800,
Immunotechs.r.o., USA)
1.3 experiment equipment
UCT80MicroCT (SCANCO Medical, CHE), DISCOVERY Dual-energy X-rays absorptionmetries, CMISA-99B figures
As analysis and management system, LE-80K ultracentrifuges, Leica TP1020 tissue processors, the full-automatic stone of Leica EG1160 types
Wax embedding machine, Leica RM2135 cycle type slicers, Leica Histobath types HI1210 stand piece machine, Leica
Histoplate HI1220 types baking piece machine, Leica EMLBSLR microscopes and photographic system, the full tissue scanning instrument of Olympus,
Olympus VS120-SL, Eppendorf 5415D supercentrifuges
1.4 Animal Models and packet
At 3 monthly age of female mice, 10% chloraldurate (0.3ml/100g) intraperitoneal injection of anesthesia rejects mouse back center flat
At the crista iliaca level of both sides under mouse hair, iodophor disinfection, aseptic condition, prone position is through back side midsection skin about 2-3cm otch
Into, move under the arcus costarum of side at 3-4 lumbar vertebraes, passivity separates waist manadesma, muscle, cut peritonaeum, separate and expose ovary, knot
Prick after fallopian tubal and peripheral vessels, extract ovary.Then offside ovary is extractd by identical method.Ensuring to extract bilateral ovaries
Afterwards, layer-by-layer suture peritonaeum is to skin, and chlorotetracycline eye ointment smears wound.Random picking 5 is only used as model group, and 5 sham-operation groups are not
Ovary is extractd, a little adipose tissue beside bilateral ovaries is only extractd.Remaining experimental mice in after 3 months again be combined tibial bone
Roll over modeling.
In March after removal ovary, toe is cut to remaining 45 mouse 1-45# is numbered, weighed, record body weight, average weight
For (31.9 ± 4.5) g, random district's groups packet is carried out with the softwares of SPASS 18, is divided into three groups：Physiological saline group, invigorating the spleen
Kidney tonifying group, QIANGGU JIAONANG group.In compound left tibias fracture surgery second day, gavage treatment is carried out, three groups are given physiology respectively
Salt solution, Jianpi Bushen, QIANGGU JIAONANG 0.2ml/ days, every group of three time point 7,14,28 days, respectively gavage 6,12,24 times.Often
Each time point each 5 mouse of group.Every group is put to death mouse to corresponding time point respectively, is drawn materials, and carries out Indexs measure.
1.5 Testing index
1.5.1 imageological examination：Left tibias fracture site X-ray checks that left tibias poroma Micro-CT scannings divide
Analysis.
1.5.2 bone histomophormetry：After iconography detection, left tibias is taken off with 14%EDTA
Calcium treatment, 20 days or so after it is calcareous take off completely after, Leica TP1020 tissue processors row serial dehydration, waxdip, embedding are cut
Piece machine is cut into 5mm thickness sections, dries, bakes piece along shin bone sagittal plane, carries out later stage Pathomorphologic credit analysis (such as HE, ABH/
OG, Trap dyeing, SABC, immunofluorescence dyeing etc.).
1.5.3 musculature slice analysis：Fixed gastrocnemius is taken out to wash through PBS, soak 1-2 hours, Leica
TP1020 tissue processors row serial dehydration, waxdip, embedding, slicer are cut into 5mm thickness sections, dry, bake along muscle coronal-plane
Piece, carries out later stage Pathomorphologic credit analysis (such as HE, immunofluorescence dyeing).
1.5.3 biomechanical is detected：The 28d poroma of Micro-CT three-dimensional reconstructions is entered by finite element analysis software
Row mechanical analysis, measurement parameter includes the rigidity of structure, cripping load, area of section and modulus of elasticity, is calculated by software.
1.6 statistical analysis：Counting index is with mean ± standard deviationRepresent.It is various by SPSS18.0 software kits
One-Way ANOVA analyses are carried out between this, t inspections are carried out between sample two-by-two.Inspection level takes bilateral α=0.05.
2 results
Influence of 2.1 Jianpi Bushens to osteoporotic fracture mice serum hormonal readiness after removal ovary：
The detection of Fig. 1 serum estradiols shows that mouse E2 contents are less than sham-operation group after removal ovary.
Strengthening spleen, tonifying kidney group, QIANGGU JIAONANG group blood serum E2 level and physiological saline group have significant difference when Fig. 2 illustrates 28 days,
Illustrate that Jianpi Bushen and QIANGGU JIAONANG can improve estrogen level after removal ovary after certain course for the treatment of, so as to slow down high conversion hysteria
The progress of osteoporosis.
The influence that 2.2 Jianpi Bushens heal to osteoporotic fracture mouse different time sections poroma after removal ovary：
Lumbar vertebra girder is substantially sparse compared with sham-operation group after the visible removal ovary of Fig. 3 Micro-CT three-dimensional reconstructions, and Fig. 4 is shown
In March after removal ovary, mouse lumbar vertebrae BMD (TV) conspicuousness can be caused to reduce (P ＜ 0.01), BV/TV, Tb.Th, Tb.N, Tb.Sp,
BMD (BV) also has obvious statistical significance (P ＜ 0.05)；Fig. 5 shin bones BV/TV, Tb.Th, Tb.N, Tb.Sp, BMD (TV) show
Work property reduction (P ＜ 0.01), BMD (BV) indifference.According to lumbar vertebrae, shin bone Micro-CT and serum estradiol result, explanation
The success of osteoporotic fracture Establishment of mouse model.
Strengthening spleen, tonifying kidney group, QIANGGU JIAONANG group mouse tibia fracture line are compared with physiological saline group mould when Fig. 6 X-Ray show 7 days
Paste, strengthening spleen, tonifying kidney and QIANGGU JIAONANG group fracture line are more obscured compared with its physiological saline group at 14 days, two groups of visible a large amount of poroma
Shadow, across fracture line, physiological saline group fracture line is more visible, and poroma shadow is less；Strengthening spleen, tonifying kidney and QIANGGU JIAONANG group at 28 days
Fracture heading line off, cortex of bone is continuous, and fuzzy fracture line, which still can be seen, in physiological saline group is present, a small amount of poroma shadow.
The visible strengthening spleen, tonifying kidney of Fig. 7 Micro-CT three-dimensional reconstructions and QIANGGU JIAONANG group 7, the form and density of 14,28 days poroma
Physiological saline group is superior to, wherein optimal with strengthening spleen, tonifying kidney group, Fig. 8 data analyses further illustrate strengthening spleen, tonifying kidney group in early stage
(7,14 day) promote the formation of mouse fracture site poroma, its TBV and Callus volume ratio (BV/TV), poroma bone density
(BMD), the index such as Connection Density (Conn.D) is superior to physiological saline group, although the data of 28 days with physiological saline group without obvious
Difference, it is considered to which fracture site may substantially heal at 21 days after each pharmaceutical intervention, and be cured substantially during physiological saline group 28 days
Close, still with the presence of part os osseum scab, thus two groups have no notable difference.But Fig. 9,10 biomethanics --- finite element analysis knot
Really, the rigidity of structure, modulus of elasticity result after display strengthening spleen, tonifying kidney group and the disconnected section of QIANGGU JIAONANG group fracture heal are higher than physiology salt
Water group, also illustrates that Jianpi Bushen and QIANGGU JIAONANG group poroma healing time and quality are superior to physiological saline group.
Influence of 2.3 Jianpi Bushens to senile osteoporosis fracture Mouse cartilage and osteoblast activity：
Fracture site is big when Figure 11 HE are dyed and Figure 12 ABH/OG dye visible strengthening spleen, tonifying kidney group, QIANGGU JIAONANG group 7 days
Cartilage proliferation is measured, and physiological saline group has no that obvious cartilage scab is formed；Strengthening spleen, tonifying kidney group articular chondrocyte apoptosis at 14 days, skeletonization is thin
Born of the same parents start increase, and physiological saline group just formed a small amount of cartilage scab, 28 days strengthening spleen, tonifying kidney groups, QIANGGU JIAONANG group fracture at 14 days
The broken ends of fractured bone heals substantially, and cortex of bone is continuous, and ossis has been led to, and the still visible os osseum scab of physiological saline group is present, and ossis is not yet complete
Lead to again, it heals postpones one week compared with Chinese medicine group.Illustrate that Chinese medicine group, especially strengthening spleen, tonifying kidney group can be raised significantly in different time sections
The activity of cartilage and Gegenbaur's cell, promotes the intramembranous ossification and entochondrostosis of osteoporotic fracture, to improve osteoporosis
Property fracture delayed union and the situation of disunion.
Influence of 2.3 Jianpi Bushens to senile osteoporosis fracture mouse osteoclast activity：
Figure 13 Trap are dyed in visible each group 7, the poroma of 14,28 days fracture sites with the presence of a large amount of osteoclasts, and
Strengthening spleen, tonifying kidney group only had a small amount of osteoclast formation at 7 days, 14,28 days when osteoclast start increase.
Figure 13 illustrates that strengthening spleen, tonifying kidney group early stage can suppress the hyperplasia of osteoclast, only a small amount of to absorb downright bad bone tissue,
And 14-28 days cartilage cells start apoptosis, Gegenbaur's cell increase, and need certain amount osteoclast apoptosis involvement cartilage cell
Absorption and poroma rebuild so that ossis is led to again, form normal bone.Therefore, Jianpi Bushen have balance Gegenbaur's cell-
Osteoclast lotus root closes relation, maintains tissue, the effect of the normal function of organ, i.e. equilibrium between yin and yang.
2.4 Jianpi Bushens promote the Study on Molecular Mechanism of senile osteoporosis union：
Figure 14 poroma β-catenin immunohistochemical stainings are visible, each Chinese medicine group treatment 7,14,28 days when poroma in have bright
Aobvious β-catenin positive expression cells, physiological saline group only has a small amount of expression, wherein, table the most obvious with strengthening spleen, tonifying kidney group
Bright strengthening spleen, tonifying kidney can effectively activate poroma β-catenin signal paths and be expressed in core and in kytoplasm.Figure 15 poroma Runx2 exempts from
Epidemic disease histochemical staining is visible, each Chinese medicine group treatment 7,14,28 days when poroma in have obvious Runx2 positive expressions cell, physiology
Salt solution group only has a small amount of expression, wherein it is the most obvious with strengthening spleen, tonifying kidney group, show that strengthening spleen, tonifying kidney can effectively activate poroma Runx2
Signal path is expressed in core.
Figure 16, the double fluorescent immunohistochemistries of 17 fracture site muscle Pax7 and Brdu are visible, compared with physiological saline group,
Strengthening spleen, tonifying kidney group has the cell of more Pax7 and Brdu double expressions when treating 7 days in fracture site muscle, show strengthening spleen, tonifying kidney
The proliferation activity of Muscle-derived Stem Cells in fracture site muscle can be promoted to a certain degree.
Figure 18, the double fluorescent immunohistochemistries of 19 fracture site muscle MyoD and Brdu are visible, are compared with physiological saline group,
At treatment 7,14 days, the cell of MyoD and Brdu double expressions substantially increased strengthening spleen, tonifying kidney group in muscle, and strengthening spleen, tonifying kidney can promote
Myoblast proliferation activity, in favor of the reparation of muscle damage.
7,14 days diastatic fractures section muscle (tibialis posterior) that breaks carries out Osteoblast Differentiation gene RT-PCR inspections after Figure 20,21 fracture
Survey, compared with physiological saline, ALP, RUNX2, AXIN2, Pax7, EN1 and BMP2, OC can be obviously promoted during strengthening spleen, tonifying kidney group 7 days
Expression；AXIN2, OPN, Pax7 expression can be promoted at 14 days.Can be obviously promoted during QIANGGU JIAONANG 7 days ALP, RUNX2,
AXIN2, Pax7, EN1 and OC expression；ALP, RUNX2, OPN, BMP2, OC, Pax7, AXIN2 can be promoted at 14 days.Illustrate strong
Spleen Bushen Prescription can promote the Osteoblast Differentiation potential of myogenic tumor for 7 days to a certain degree in early stage, participate in repair of fractured bones.
In summary each experimental result, show that strengthening spleen, tonifying kidney can improve estrogen level after removal ovary, improves high conversion
The osteoporosis that type bone loss is caused；β-catenin signal paths are mediated to promote fracture site cartilage, Gegenbaur's cell to live simultaneously
Property, promote in film and entochondrostosis；Osteoclast activity is balanced, bone remoulding is participated in；And may be by promoting fracture bone nearby
The propagation of Muscle-derived Stem Cells in bone flesh, promotes Muscle-derived Stem Cells to break up to a certain extent to Osteoblast Specific, participates in
The reparation of fracture.
Claims (7)
1. a kind of compound Chinese medicinal preparation for treating osteoporotic fracture, it is characterised in that auxiliary by strengthening spleen, tonifying kidney Chinese medicine and medicine
Material is prepared from, and the composition and its parts by weight of the strengthening spleen, tonifying kidney Chinese medicine are：Radix Codonopsis 6-30, wilsonii 6-30, rhizome of davallia 6-30,
Barrenwort 6-30, red sage root 6-15, levisticum 3-12.
2. the compound Chinese medicinal preparation for the treatment of osteoporotic fracture according to claim 1, it is characterised in that the invigorating the spleen
The composition and its parts by weight of kidney-nourishing tcm drug be：Radix Codonopsis 5.5-15, wilsonii 5.5-15, rhizome of davallia 5.5-15, barrenwort 5.5-15,
Red sage root 4.5-12, levisticum 3-9.
3. the compound Chinese medicinal preparation for the treatment of osteoporotic fracture according to claim 1, it is characterised in that the invigorating the spleen
The composition and its parts by weight of kidney-nourishing tcm drug be：Radix Codonopsis 5-12, wilsonii 5-12, rhizome of davallia 5-12, barrenwort 5-12, red sage root 4-9,
Levisticum 3-6.
4. the preparation method of the compound Chinese medicinal preparation of the treatment osteoporotic fracture according to claim 1 or 2 or 3, its
It is characterised by, comprises the technical steps that：
1. weigh each medicinal material by prescription parts by weight, soak 1h, decoct 3 times, decoct 1h every time, one decocts and adds water 14 times, two, three decoct plus
10 times of water, merges decoction liquor, filters, at a temperature of 60~70 DEG C, and filtrate is concentrated into the leaching that relative density is 1.05~1.07
Cream；
2. ethanol is added in above-mentioned 1. medicinal extract liquid, is 60% to concentration of alcohol, stands overnight, alcohol precipitation, filtered, filtrate is 60~70
Ethanol is reclaimed at a temperature of DEG C, and is concentrated into the equivalent extract that relative density is 1.35~1.40；
3. above-mentioned 2. equivalent extract is dried under reduced pressure at 70~80 DEG C, is ground into fine powder, is crossed 60 mesh sieves, is obtained extract powder；
4. extract powder adds pharmaceutic adjuvant, mixes, and granulation is pressed into piece；Or granule, capsule, mixture or powder is made.
5. the preparation method of the compound Chinese medicinal preparation of the treatment primary osteoporosis as described in claim 4, its feature exists
In filler is MCC；Disintegrant is Ac-Di-Sol.
6. the answering in the medicine for preparing treatment osteoporotic fracture of the compound Chinese medicinal preparation described in claim 1 or 2 or 3
With.
7. application according to claim 6, it is characterised in that the compound Chinese medicinal preparation is believed by acting on β-Catenin
Number path promotes the propagation and Osteoblast Differentiation of Muscle-derived Stem Cells, accelerates the healing of osteoporotic fracture.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112807368A (en) * | 2021-01-28 | 2021-05-18 | 福建中医药大学 | Medicine composition for treating osteoporotic fracture and preparation method and application thereof |
| CN113361182A (en) * | 2021-07-02 | 2021-09-07 | 哈尔滨理工大学 | Fracture healing simulation method based on immune system effect |
| CN114767735A (en) * | 2022-04-02 | 2022-07-22 | 上海中医药大学附属龙华医院 | Chinese medicinal prescription for invigorating spleen and kidney and its product for improving sarcopenia and muscular atrophy after fracture |
| CN115436529A (en) * | 2022-10-17 | 2022-12-06 | 上海中医药大学附属龙华医院 | Method for constructing HPLC (high Performance liquid chromatography) fingerprint of compound spleen-tonifying and kidney-tonifying preparation and standard fingerprint |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112807368A (en) * | 2021-01-28 | 2021-05-18 | 福建中医药大学 | Medicine composition for treating osteoporotic fracture and preparation method and application thereof |
| CN113361182A (en) * | 2021-07-02 | 2021-09-07 | 哈尔滨理工大学 | Fracture healing simulation method based on immune system effect |
| CN114767735A (en) * | 2022-04-02 | 2022-07-22 | 上海中医药大学附属龙华医院 | Chinese medicinal prescription for invigorating spleen and kidney and its product for improving sarcopenia and muscular atrophy after fracture |
| CN115436529A (en) * | 2022-10-17 | 2022-12-06 | 上海中医药大学附属龙华医院 | Method for constructing HPLC (high Performance liquid chromatography) fingerprint of compound spleen-tonifying and kidney-tonifying preparation and standard fingerprint |
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