CN107929310A - A kind of preparation method of the medicine of promoting bone growing protein expression accelerating union of bone fracture - Google Patents
A kind of preparation method of the medicine of promoting bone growing protein expression accelerating union of bone fracture Download PDFInfo
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- CN107929310A CN107929310A CN201711405606.3A CN201711405606A CN107929310A CN 107929310 A CN107929310 A CN 107929310A CN 201711405606 A CN201711405606 A CN 201711405606A CN 107929310 A CN107929310 A CN 107929310A
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- sodium alginate
- bone
- sodium
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- medicine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/734—Alginic acid
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
Abstract
A kind of medicine of promoting bone growing protein expression accelerating union of bone fracture, it is to be prepared by sodium alginate through carboxy methylation.The sodium hydroxide liquid that 15g (2mol/L) is added by every 100g sodium alginates is uniformly mixed, and 0.5h is stirred at 35 DEG C；Then the mixture of chloroacetic acid 20g and sodium hydroxide 20g are added by every 100g sodium alginates, stirring reaction 3h, obtains carboxymethyl sodium alginate product under the conditions of 70 80 DEG C.In 95% ethanol solution sodium alginate, sodium hydroxide, the method for one pot of stir-fry of chloroacetic acid can also be taken to prepare.By quality: quality: volume=1: take sodium alginate, sodium hydroxide, chloroacetic acid at 0.35: 0.30, the volume fraction for being put into 2 times of volumes are in 95% ethanol solution, in 50 DEG C of etherification temperature, etherification time 3h, under the conditions of reacted.Reaction product is washed with 95% ethanol, precipitates 24h, product drying, obtains carboxymethyl sodium alginate product.Obtained carboxymethyl sodium alginate is in promoting bone growing protein expression, for treating and preventing the medicine of fracture, bone nonunion, caput femoris necrosis, osteoporosis.
Description
Technical field
The invention belongs to clinical medicine medication, particularly relate to it is a kind of be suitable for fracture, bone nonunion, caput femoris necrosis,
The medicine of the treatment and prevention of osteoporosis.
Background technology
With the development of society, the prosperity of transportation, the frequent development of various movements, various wounds, fracture are
As common clinical and frequently-occurring disease, the health of the serious danger association mankind and the labour capacity for influencing people.How bone is promoted early
Folding healing, is the emphasis problem in orthopedics and traumatology field.
Union is extremely complex biology repair process.Clinically apply a variety of sides for promoting union
The problem of method, but fracture delayed union, disunion, is not fully solved yet.In recent years, due to the development and application of gene technology, people
To union understanding from cell biology to molecular biology it is horizontal deeply, and with the continuous hair of molecular biology
Exhibition, it has been recognized that union is related with a variety of biotic factors, in addition to the whole body factor such as endocrine, metabolic factor, fracture office
Still there is substantial amounts of growth factor in portion, and important adjustment effect is played to union.
Bone Morphogenetic Protein (bone morphogenetie protein, abbreviation BMP) family belongs to transforming growth factor
(TGF-β) superfamily, initially extracts from the bone matrix of ox, in vivo can induce ectopic osteogenesis, promotes union
Ability.Experimental studies have found that the effect of bone induced by bone morphogenetic protein marrow stromal cells into osteoblasts cell differentiation is probably its promotion
One of bon e formation, the mechanism of action for treating Related Bone Skeletal Diseases.
The content of the invention
It is an object of the invention to provide a kind of preparation method of carboxymethyl sodium alginate for the purpose of the present invention.It is to provide one
Kind preparation method is simple, and raw material sources widely treat and prevent the medicine of fracture.
It is an advantage of the invention that preparation method is simple, raw material sources are wide.
The purpose of the present invention can be realized by following technique measures：
The medicine of the treatment and prevention fracture of the present invention is that sodium alginate is made through carboxy methylation.Its preparation method is as follows：
1st, prepared by carboxy methylation：The sodium hydroxide liquid 380-400ml that 15g (2mol/L) is added by every 100g sodium alginates is mixed
Uniformly, 0.5h is stirred at 35 DEG C；Then the mixing of chloroacetic acid 20g and sodium hydroxide 20g are added by every 100g sodium alginates
Thing, stirring reaction 3h, reaction product are washed with 95% ethanol under the conditions of 70-80 DEG C, are precipitated 24h, are obtained carboxymethyl alginic acid
Sodium product, product drying.
The mass ratio of sodium hydroxide and sodium alginate is 0.35-0.4: 1.0；The mass ratio of monoxone and sodium alginate is
0.2∶1.0。
2nd, one pot of stir-fry method：By quality: quality: volume=1: take sodium alginate, sodium hydroxide, a chloroethene at 0.35: 0.30
Acid, be put into 2 times of volumes volume fraction be 95% ethanol solution in, under the conditions of 50 DEG C of etherification temperature, etherification time 3h into
Row reaction.Reaction product is washed with 95% ethanol, precipitates 24h, product drying, obtains carboxymethyl sodium alginate product.
Carboxymethyl sodium alginate, it is characterised in that the general formula of molecular structure of the carboxymethyl sodium alginate is： [C5H5O4
(COONa) (CH2COONa) 2] n, in its molecular structure, contains carboxymethyl, n 1-30.
The effect of in order to further verify finished product preparation of the present invention, we will prepare in above-mentioned specific preparation method 1-3
Medicine carried out corresponding animal experiment, now result is reported as follows.
Reagent：Bone morphogenesis protein-2 (BMP-2) antibody is purchased from Beijing Bo Aosen Bioisystech Co., Ltd
Animal：Kunming mice 30, weight 18-22g, male.
Method：30 20~30g of weight, 2~3 monthly age Kunming small white mouse femur bones are made animal fracture model, are divided into
Two groups of A, B.The daily carboxymethyl sodium alginate 0.1g gavages of A groups every, the daily 0.1g glucose gavages of B groups every, every group of mouse
5 are respectively put to death respectively at 7,14 28d.Take small white mouse femur pathological section.Sample decalcification after the fixation of 10% formaldehyde, is immunized
Histochemical staining.As a result two groups of significant differences, A groups can form continuity bone for 3-4 weeks and be crazy about, clinical healing, most short 14 days can shape
It is crazy about into continuous bone.
As a result：The immuno positive product expression of BMP-2 albumen in bone matrix and osteoblast kytoplasm in, in brown color.
The expression of BMP-2 albumen is judged using semiquantitative method：Select 10 high power fields, the positive reaction cell number ＜ of colour developing
25% for+, 25~50% are ++, ＞ 75% is +++, no obvious positive reaction cell for-.The statistical analysis of enumeration data
Using Chi-square Test.Test stone α=0.05.
1 postoperative 7d of table, the expression of two groups of BMP-2 albumen of 15d, 21d compare (n=15)
。
Brief description of the drawings
Fig. 1：Postoperative 7d treatment groups BMP-2 protein expressions are higher than blank group (p ＜ 0.01)；7d treatment groups BMP-2 albumen
Expression (sp, 400 ×).
Fig. 2：Postoperative 7d blank groups BMP-2 protein expressions are less than blank group (p ＜ 0.01)；7d blank group BMP-2 albumen
Expression (sp, 400 ×).
Fig. 3：Postoperative 14d treatment groups BMP-2 protein expressions are higher than blank group (p ＜ 0.01)；14d treatment groups BMP-2 albumen
Expression (sp, 400 ×).
Fig. 4：Postoperative 14d blank groups BMP-2 protein expressions are less than in blank group (p ＜ 0.01)；14d blank group BMP-2 eggs
White expression (sp, 400 ×).
Fig. 5：Postoperative 21d treatment groups BMP-2 protein expressions are higher than blank group (p ＜ 0.01)；21d treatment groups BMP-2 albumen
Expression (sp, 400 ×).
Fig. 6：Postoperative 21d blank groups BMP-2 protein expressions are less than in blank group (p ＜ 0.01), 21d blank group BMP-2 eggs
White expression (sp, 400 ×).
Embodiment
It is the specific embodiment of present invention below, the skill of technical problem is solved in present specification for illustrating
Art scheme.
Embodiment 1
It is prepared by carboxy methylation：The sodium hydroxide liquid 380-400ml mixing that 15g (2mol/L) is added by every 100g sodium alginates is equal
It is even, stir 0.5h at 35 DEG C；Then the mixing of chloroacetic acid 20g and sodium hydroxide 20g are added by every 100g sodium alginates
Thing, stirring reaction 3h, reaction product are washed with 95% ethanol under the conditions of 70-80 DEG C, are precipitated 24h, are obtained carboxymethyl alginic acid
Sodium product, product drying.
The mass ratio of sodium hydroxide and sodium alginate is 0.35-0.4: 1.0；The mass ratio of monoxone and sodium alginate is
0.2∶1.0。
Embodiment 2
One pot of stir-fry method：By quality: quality: volume=1: take sodium alginate, sodium hydroxide, chloroacetic acid at 0.35: 0.30, is put into
The volume fraction of 2 times of volumes is in 95% ethanol solution, is reacted under the conditions of 50 DEG C of etherification temperature, etherification time 3h.
Reaction product is washed with 95% ethanol, precipitates 24h, product drying, obtains carboxymethyl sodium alginate product.
Claims (2)
1. carboxymethyl sodium alginate is preparing promoting bone growing protein expression, it is bad to treat and prevent fracture, bone nonunion, femoral head
Extremely, the application in the medicine of osteoporosis, it is characterised in that：The preparation method of carboxymethyl sodium alginate is as follows：By quality: quality
: volume=1: take sodium alginate, sodium hydroxide, chloroacetic acid at 0.35: 0.30, the volume fraction for being put into 2 times of volumes are 95%
In ethanol solution, reacted under the conditions of 50 DEG C of etherification temperature, etherification time 3h, reaction product is washed with 95% ethanol, is sunk
Shallow lake 24h, product drying, obtains carboxymethyl sodium alginate product.
2. such as claim 1-2 any one of them applications, it is characterised in that the general formula of molecular structure of the carboxymethyl sodium alginate
For：[C5H5O4(COONa)(CH2COONa)2]n, in its molecular structure, contain carboxymethyl, n 1-30.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201711405606.3A CN107929310A (en) | 2013-04-24 | 2013-04-24 | A kind of preparation method of the medicine of promoting bone growing protein expression accelerating union of bone fracture |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711405606.3A CN107929310A (en) | 2013-04-24 | 2013-04-24 | A kind of preparation method of the medicine of promoting bone growing protein expression accelerating union of bone fracture |
| CN201310142747.6A CN103936881B (en) | 2013-04-24 | 2013-04-24 | A kind of preparation method of the drug of promoting bone growing protein expression accelerating union of bone fracture |
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| CN201310142747.6A Division CN103936881B (en) | 2013-04-24 | 2013-04-24 | A kind of preparation method of the drug of promoting bone growing protein expression accelerating union of bone fracture |
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| CN107929310A true CN107929310A (en) | 2018-04-20 |
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| CN201711407772.7A Pending CN107875167A (en) | 2013-04-24 | 2013-04-24 | A kind of preparation method of the medicine of promoting bone growing protein expression accelerating union of bone fracture |
| CN201711405606.3A Pending CN107929310A (en) | 2013-04-24 | 2013-04-24 | A kind of preparation method of the medicine of promoting bone growing protein expression accelerating union of bone fracture |
| CN201310142747.6A Expired - Fee Related CN103936881B (en) | 2013-04-24 | 2013-04-24 | A kind of preparation method of the drug of promoting bone growing protein expression accelerating union of bone fracture |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008127290A2 (en) * | 2006-10-12 | 2008-10-23 | The Johns Hopkins University | Alginate and alginate lyase compositions and methods of use |
| CN102349929A (en) * | 2011-09-28 | 2012-02-15 | 郭宏昌 | Drug for treating and preventing fracture |
| CN103830266A (en) * | 2013-04-24 | 2014-06-04 | 杨亚勤 | Preparation method and application of carboxymethylated derivative of partially-oxidized sodium alginate |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100435858C (en) * | 2006-10-23 | 2008-11-26 | 厦门大学 | The composite skeletal agglutinant made by sodium alginate-carboxyl methyl cellulose and its preparation method |
| CN101787267B (en) * | 2010-03-17 | 2012-10-17 | 西南石油大学 | Double-modified starch fluid loss additive used for oil and gas field drilling fluid and preparation method thereof |
| CN103041442A (en) * | 2013-01-23 | 2013-04-17 | 厦门大学 | Sodium alginate-based bone binding agent and preparation method thereof |
-
2013
- 2013-04-24 CN CN201711407772.7A patent/CN107875167A/en active Pending
- 2013-04-24 CN CN201711405606.3A patent/CN107929310A/en active Pending
- 2013-04-24 CN CN201310142747.6A patent/CN103936881B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008127290A2 (en) * | 2006-10-12 | 2008-10-23 | The Johns Hopkins University | Alginate and alginate lyase compositions and methods of use |
| CN102349929A (en) * | 2011-09-28 | 2012-02-15 | 郭宏昌 | Drug for treating and preventing fracture |
| CN103830266A (en) * | 2013-04-24 | 2014-06-04 | 杨亚勤 | Preparation method and application of carboxymethylated derivative of partially-oxidized sodium alginate |
Non-Patent Citations (4)
| Title |
|---|
| 司艳莉等: "海藻酸多糖衍生物治疗大鼠骨质疏松", 《中国组织工程研究与临床康复》 * |
| 王伟: "骨形成蛋白-2诱导骨形成研究进展", 《口腔材料器械杂志》 * |
| 钟超凡等: "羧化改性海藻酸钠沉淀吸附铜离子的研究", 《湘潭大学自然科学学报》 * |
| 陈玺等: "海藻酸钠在临床的应用", 《中国医院药学杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107875167A (en) | 2018-04-06 |
| CN103936881B (en) | 2018-06-19 |
| CN103936881A (en) | 2014-07-23 |
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Application publication date: 20180420 |
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