CN104558620A - Preparation and usage of novel dendrimer - Google Patents
Preparation and usage of novel dendrimer Download PDFInfo
- Publication number
- CN104558620A CN104558620A CN201310481092.5A CN201310481092A CN104558620A CN 104558620 A CN104558620 A CN 104558620A CN 201310481092 A CN201310481092 A CN 201310481092A CN 104558620 A CN104558620 A CN 104558620A
- Authority
- CN
- China
- Prior art keywords
- compound
- dendritic macromole
- tinea ranae
- compd
- dendrimer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses preparation and usage of a novel tadpole-shaped dendrimer-containing compound. The tadpole-shaped compound adopts a dendrimer as the head part and a hydrophilic chain compound as the tail part. The invention discloses the preparation method and usage of the novel tadpole-shaped dendrimer-containing compound. The novel tadpole-shaped dendrimer-containing compound can facilitate fertilization to take place in a human or animal body, that is, the novel tadpole-shaped dendrimer-containing compound can improve the ovum fertility rate during the normal fertility process.
Description
Technical field
The Tinea Ranae shape that the invention discloses a kind of novelty contains preparation and the purposes of the compound of dendritic macromole, the compound of this Tinea Ranae shape take dendritic macromole as head, with the compound that hydrophilic chain compound is afterbody, the invention discloses Preparation Method And The Use.The compound of this Tinea Ranae shape can improve the rate of fertilization of ovum in the internal fertilization of human or animal and normal reproduction process.
Background technology
At present, because environmental pollution and life stress increase day by day, young man and wife's incidence of infertility significantly increases, and not only makes some families be perplexed, also brings very large unstability to society.Some wild animals in imminent danger, due to can not effective fertility, cause the extinction of species.The success rate of external fertilization only rests on about 50%, and operates lengthy and tedious, cannot efficiently and take time and effort consumptive material.The present inventor has invented a kind of brand-new Tinea Ranae shape compound, this Tinea Ranae shape compound can make sperm in vivo in fertilization process, be combined with ovum readily through fallopian tube, combination rate exceedes common more than 3 times of becoming pregnant, and namely this Tinea Ranae shape compound can make human or animal have the ability breeding filial generation more strongly in non-external fertilization and normal reproduction process.
This Tinea Ranae shape compound prepared by the present invention can at utmost make sperm be combined with ovum after mammal sexual intercourse, has the ability improving ovum fertilization rate in the natural growing process in Mammalian Reproduction field.The zoopery that the compounds of this invention carries out shows, the new compound of this similar Tinea Ranae shape that has a beginning and an end makes the ovum fertilization rate of mice at least improve 3 times in the internal fertilization and normal reproduction process of mice.
Summary of the invention
A kind of new compound containing dendritic macromole of the similar Tinea Ranae shape that has a beginning and an end in the structure be shown below, the dendritic macromole of its feature to be head be approximate sphericity is formed, afterbody is made up of one section of linear hydrophilic chain compound, form a compound like Tinea Ranae shape, its structure is as follows:
In structure
S-S in structure is the kernel of dendritic macromole, the m of the height cladodification of this representation approximate sphericity is for dendritic macromole, wherein m is the algebraically of dendritic macromole, m gets the multiple of integer between 0-50 and 0.5, and the Linker in structure represents a kind of branch structure compound with three Ge Zhicha branches, a branch is connected with hydrophilic chain, another two branches are connected with the core chemistry of half dendritic macromole, formed one like Tinea Ranae shape containing dendritic macromole be head, hydrophilic chain compound is the compound of afterbody.This branched compound contains the active group that can react with-SH.This branched compound, preferably
，
。
Hydrophilic chain Hydrophilic chain in the structure of compound is the compound of one section of hydrophilic long-chain shape, is selected from polyvinyl alcohol, polysaccharide, Polyethylene Glycol, polypyrrole alkane ketone, polyethers, polyoxyethylene block copolymer, or their copolymer.The preparation method of the compound that the present invention invents, is characterized in that:
1) will be with S-S the dendritic macromole G of core
m, wherein m is the algebraically of dendritic macromole, and m gets the multiple of integer between 0-50 and 0.5, G
mbe decomposed under the catalysis of vitamin C, dithiothreitol, DTT or sodium sulfite and be good for half active dendritic macromole G with SH
ma;
2) branched compound L inker and linear hydrophilic chain compound H ydrophilic Chain side coupling generate the ol cpds B with apparatus derivatorius;
3) compd A stirred overnight in the solvent of 0-20 degree of the compd B of a times mole and twice mole is reacted, and the both sides of branch are reacted with the SH of the kernel of half dendrimer A respectively, are obtained by reacting the Compound C of Tinea Ranae shape containing dendritic macromole;
4) will Compound C lyophilizing 24-96 hour in vacuum drying oven of the Tinea Ranae shape of gained be prepared, obtain final products for subsequent use;
React described structure as follows
Dendrimer compound Gm:
；
Compd A:
；
Compd B:
Wherein this structure
Belong to the structure in Linker structure;
Compound C:
。Wherein chemical step 1-4 selects solvent to be selected from: methyl ether, ether, petroleum ether, benzene, toluene, pyridine, oxolane, trifluoroacetic acid, chloroform, carbon tetrachloride, 3-(2-pyridine dimercapto) propanoic acid N-hydroxy-succinamide ester, tricresyl phosphate (2-chloroethyl) ester, dichloromethane, methanol, ethanol, dichloromethane, dimethyl sulfoxide, N, one or more in dinethylformamide, N, N'-dicyclohexylcarbodiimide.This new use of a compound having a beginning and an end similar Tinea Ranae shape is greatly promote that sperm is combined with ovum in the internal fertilization and normal reproduction process of human or animal, makes it be very easy to form germ cell.Compound of the present invention can make the ovum fertilization rate of human or animal at least improve 3 times.
Preparation method of the present invention is specific as follows:
1) will be with S-S the dendritic macromole G of core
m(commercially available), wherein m is the algebraically of dendritic macromole, and m gets the multiple of integer between 0-50 and 0.5, G
munder the catalysis of vitamin C (commercially available), dithiothreitol, DTT (commercially available) or sodium sulfite (commercially available), in organic solution, reduction decomposition is be good for half active dendritic macromole G with SH
ma;
2) branched compound L inker(is commercially available, also can prepare) (commercially available with one section of linear hydrophilic chain compound, also can prepare) be under the condition of 5-9 at PH, reaction coupling in normal-temperature reaction 1-48 hour generates the compd B with branched structure, and then lyophilizing is for subsequent use;
3) compd A of the compd B of a times mole and twice mole spends the night low speed 50rpm-500rpm stirring reaction in the solvent of 0-20 degree, is obtained by reacting the dendrimer C containing medicines structure;
4) by prepare gained directly to wash rear lyophilizing with the non-medicines structure soluble in water dendrimer C that is core for subsequent use; Or add freeze drying protectant (potassium sorbate, mannitol, sodium carboxymethyl cellulose etc.), in vacuum drying oven, lyophilizing 24-96 hour, obtains final products for subsequent use;
For subsequent use after Compound C lyophilizing, for animal regulation and control sex after weigh.
The compound containing dendritic macromole of Tinea Ranae shape of the present invention farthest can promote the combination of X sperm and ovum after human or animal's sexual intercourse, the combination of very big raising y sperm and ovum, has the ability improving ovum fertilization rate in the natural growing process in human or animal's field of reproduction.Compound of the present invention also can be used for the adjuvant application of some medicines due to speciality own or applies as genophore.
At present, because environmental pollution and life stress increase day by day, young man and wife's incidence of infertility significantly increases, and not only makes some families be perplexed, also brings very large unstability to society.Some wild animals in imminent danger, due to can not effective fertility, cause the extinction of species.The success rate of external fertilization only rests on about 50%, and operates lengthy and tedious, cannot efficiently and take time and effort consumptive material.The present inventor has invented a kind of brand-new Tinea Ranae shape compound, this Tinea Ranae shape compound can make sperm in vivo in fertilization process, be combined with ovum readily through fallopian tube, combination rate exceedes common more than 3 times of becoming pregnant, and namely this Tinea Ranae shape compound can make human or animal have the ability breeding filial generation more strongly in non-external fertilization and normal reproduction process.
This Tinea Ranae shape compound prepared by the present invention can at utmost make sperm be combined with ovum after mammal sexual intercourse, has the ability improving ovum fertilization rate in the natural growing process in Mammalian Reproduction field.The zoopery that the compounds of this invention carries out shows, the new compound of this similar Tinea Ranae shape that has a beginning and an end makes the ovum fertilization rate of mice at least improve 3 times in the internal fertilization and normal reproduction process of mice.
In sum, Tinea Ranae shape compound of the present invention invention and application will bring great social meaning and scientific meaning.
accompanying drawing illustrates:
fig. 1the nuclear magnetic resonance map of the end-product of embodiment 1.
fig. 2the nuclear magnetic resonance map of the end-product of embodiment 2.
Detailed description of the invention
Specific embodiment is described in further detail the present invention below, but the present invention not only limits to following examples.
Preparation embodiment is as follows:
embodiment 1
1) the dendritic macromole polyamide-amine G3(taking S-S as core is purchased), under the catalysis of sodium sulfite (being purchased) 24 hours in dichloromethane solution reduction decomposition be good for half active dendritic macromole G with SH
3;
Be reduced to
2) branched compound L inker(is commercially available, also can prepare) be under the condition of 8 at PH, under normal temperature condition, be that the Polyethylene Glycol (being purchased) ended up reacts and within 20 hours, reacts coupling and generate compd B with branched structure with methoxyl group with the other end of an end band carboxyl, then lyophilizing is for subsequent use;
+
N approximates 100.
3) compd B of a mole and the compd A of two moles are at the N of 10 degree, and spend the night in N'-dicyclohexylcarbodiimide and chloroformic solution low speed 100rpm stirring reaction, is obtained by reacting the dendrimer C containing medicines structure;
+
4) by after preparing the washing in aqueous with the medicines structure not soluble in water dendrimer C that is core of gained, in vacuum drying oven, lyophilizing 48 hours, obtains final products for subsequent use;
embodiment 2
1) the dendritic macromole polyamide-amine G2(taking S-S as core is purchased), under the catalysis of vitamin C (being purchased) 24 hours in dimethyl sulphoxide solution reduction decomposition be good for half active dendritic macromole G2 with SH;
reduction
2) branched compound L inkerA(is commercially available, also can prepare) at N, adding acetic anhydride under dinethylformamide and trifluoroacetic acid catalysis, to generate LinkerB(also commercially available), then LinkerB is under the condition of 6.5 at PH, react with the Polyethylene Glycol (being purchased) that the other end of amino ends up with methoxyl group with one end under room temperature and within 24 hours, react coupling and generate compd B with branched structure, then lyophilizing is for subsequent use;
，
（linkerA）
TFA；anhydr；DMF
（linkerB）
+
N approximates 200
3) compd B of a mole and the compd A of two moles spend the night low speed 200rpm stirring reaction in the aqueous solution of the petroleum ether of 20 degree, are obtained by reacting the dendrimer C containing medicines structure;
4) by after preparing the washing in aqueous with the non-medicines structure soluble in water dendrimer C that is core of gained, in vacuum drying oven, lyophilizing 24 hours, obtains final products for subsequent use;
effect experimental is as follows:
(molecular weight is 5000 for the lyophilizing sample prepared by embodiment 1-2 and Polyethylene Glycol, be available commercially from sigma) and dendritic macromole polyamide amine PAMAM G3(be available commercially from sigma) all weigh identical weight, the thing medication group of 10mg/100ml is configured to distilled water solution, compare group with distilled water, investigate the compounds of this invention to the effect of rate of fertilization.
Embodiment is tested:
Laboratory animal and grouping
Buy and be used for NIH mice in zooperal 7 week age, male and female are normal after separating raises for experiment after 2 weeks, and adapt to the environment of experiment with this, mice freely takes food, drink water, every day changes fresh water, changes bedding and padding 1 time weekly.Foodstuff amount through observation Mus is every every day of 5 g/().By the method for random packet, laboratory animal is divided into 5 groups, is respectively matched group and 4 medication groups, often organize each 40 NIH female mices, be divided into medication group 4 groups, be specially embodiment 1-2 group, Polyethylene Glycol group, PAMAM(G3) group, and blank group.
The foundation of animal model
Fixing mice, the vaginal orifice of all for medication group 4 groups female Mus is all instilled the pharmaceutical aqueous solution of 3 corresponding medicines, concentration is 10mg/100ml, is respectively embodiment 1, embodiment 2, Polyethylene Glycol group, PAMAM(G3) aqueous solution organized.Matched group distilled water instills.Then immediately by male Mus and female Mus with cage 2 days, wherein male Mus and female Mus ratio are 1:1, namely often organize and all put into 40 male Mus, divide cage after 1 day.Female Mus raises 2 months, normally feeds, and notes collecting and often organizes and newly give birth to mice, so as not to hinder by adult rats.Newborn mice number and sex is added up after February.
Experimental result
Experimental result is in table 1
The sex of the new fertility mice that table 1 is respectively organized and number
| Group | New fertility male mice | New fertility female mice | Fertility total mice order |
| Normal group | 5 | 5 | 10 |
| Embodiment 1 group | 15 | 18 | 33 |
| Embodiment 2 groups | 15 | 17 | 32 |
| Polyethylene Glycol group | 4 | 5 | 9 |
| PAMAM group | 5 | 4 | 9 |
As can be seen from experimental result, after employing the medicine of embodiment, the mice number of fertility exceeds Normal group more than 3 times, can find out that the rate of fertilization of the ovum of the animal employing compound of the present invention has been enhanced more than three times.
Claims (10)
1. a kind of new compound containing dendritic macromole of the similar Tinea Ranae shape that has a beginning and an end in the structure be shown below, the dendritic macromole of its feature to be head be approximate sphericity is formed, afterbody is made up of one section of linear hydrophilic chain compound, form a compound like Tinea Ranae shape, its structure is as follows:
。
In the structure of the 2. compound of claim 1
Representative take S-S as kernel, and the m of the height cladodification of approximate sphericity is for dendritic macromole, and wherein m is the algebraically of dendritic macromole, and m gets the multiple of integer between 0-50 and 0.5.
3. the compound of claim 1, Linker wherein in structure represents a kind of branch structure compound with three Ge Zhicha branches, a branch is connected with hydrophilic chain, another two branches are connected with the core chemistry of half dendritic macromole, formed one like Tinea Ranae shape containing dendritic macromole be head, hydrophilic chain compound is the compound of afterbody.
4. the compound of claim 1, the hydrophilic chain in the structure of compound is the compound of one section of hydrophilic long-chain shape, is selected from polyvinyl alcohol, polysaccharide, Polyethylene Glycol, polypyrrole alkane ketone, polyethers, polyoxyethylene block copolymer, or their copolymer.
5. the branched compound of claim 3, this branched compound contains the active group that can react with-SH.
6. the branched compound of claim 5, preferably
，
。
7. as claim 1-6 the present invention the preparation method of compound of inventing, it is characterized in that:
1) will be with S-S the dendritic macromole G of core
m, wherein m is the algebraically of dendritic macromole, and m gets the multiple of integer between 0-50 and 0.5, G
mbe decomposed under the catalysis of vitamin C, dithiothreitol, DTT or sodium sulfite and be good for half active dendritic macromole G with SH
ma;
2) branched compound L inker and linear hydrophilic chain compound H ydrophilic Chain side coupling generate the ol cpds B with apparatus derivatorius;
3) compd A stirred overnight in the solvent of 0-20 degree of the compd B of a times mole and twice mole is reacted, and the both sides of branch are reacted with the SH of the kernel of half dendrimer A respectively, are obtained by reacting the Compound C of Tinea Ranae shape containing dendritic macromole;
4) will Compound C lyophilizing 24-96 hour in vacuum drying oven of the Tinea Ranae shape of gained be prepared, obtain final products for subsequent use;
React described structure as follows
Dendrimer compound Gm:
；
Compd A:
；
Compd B:
Wherein this structure
Belong to the structure in Linker structure;
Compound C:
。
8. the method for claim 7, wherein said chemical step 1-4 selects solvent to be selected from: methyl ether, ether, petroleum ether, benzene, toluene, pyridine, oxolane, trifluoroacetic acid, chloroform, carbon tetrachloride, 3-(2-pyridine dimercapto) propanoic acid N-hydroxy-succinamide ester, tricresyl phosphate (2-chloroethyl) ester, dichloromethane, methanol, ethanol, dichloromethane, dimethyl sulfoxide, N, one or more in dinethylformamide, N, N'-dicyclohexylcarbodiimide.
9. the purposes of the compound of claim 1, this new use of a compound having a beginning and an end similar Tinea Ranae shape is greatly promote that sperm is combined with ovum in the internal fertilization and normal reproduction process of human or animal, makes it be very easy to form germ cell.
10. the purposes of the compound of claim 9, the compound of this invention can make the ovum fertilization rate of human or animal at least improve 3 times.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310481092.5A CN104558620A (en) | 2013-10-15 | 2013-10-15 | Preparation and usage of novel dendrimer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310481092.5A CN104558620A (en) | 2013-10-15 | 2013-10-15 | Preparation and usage of novel dendrimer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104558620A true CN104558620A (en) | 2015-04-29 |
Family
ID=53075752
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310481092.5A Pending CN104558620A (en) | 2013-10-15 | 2013-10-15 | Preparation and usage of novel dendrimer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104558620A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105085930A (en) * | 2013-11-08 | 2015-11-25 | 韩冰 | Novel dendritic macromolecule and its preparation method and use |
| CN105085931A (en) * | 2013-11-08 | 2015-11-25 | 韩冰 | Novel dendritic macromolecule and its preparation method and use |
| CN106046387A (en) * | 2015-04-15 | 2016-10-26 | 韩冰 | Novel high-efficiency gene vector, and preparation and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103127526A (en) * | 2013-02-27 | 2013-06-05 | 万礼 | Tree-like polymer targeting nanometer drug delivery carrier and its preparation method |
-
2013
- 2013-10-15 CN CN201310481092.5A patent/CN104558620A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103127526A (en) * | 2013-02-27 | 2013-06-05 | 万礼 | Tree-like polymer targeting nanometer drug delivery carrier and its preparation method |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105085930A (en) * | 2013-11-08 | 2015-11-25 | 韩冰 | Novel dendritic macromolecule and its preparation method and use |
| CN105085931A (en) * | 2013-11-08 | 2015-11-25 | 韩冰 | Novel dendritic macromolecule and its preparation method and use |
| CN106046387A (en) * | 2015-04-15 | 2016-10-26 | 韩冰 | Novel high-efficiency gene vector, and preparation and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yu et al. | Porcine zygote injection with Cas9/sgRNA results in DMD-modified pig with muscle dystrophy | |
| CN104130973B (en) | For the method for Ovine Oocytes in Vitro Maturation and pretreatment fluid and test kit | |
| CN104558620A (en) | Preparation and usage of novel dendrimer | |
| CN104558626A (en) | Preparation and usage of novel dendrimer | |
| Zhu et al. | Targeted delivery of mannosylated nanoparticles improve prophylactic efficacy of immersion vaccine against fish viral disease | |
| Hassanein et al. | Efficiency of GnRH–loaded chitosan nanoparticles for inducing LH secretion and fertile ovulations in protocols for artificial insemination in rabbit does | |
| CN104558625A (en) | Novel dendrimer as well as preparation and application thereof | |
| CN103694107A (en) | Preparation method of feed additive calcium beta-hydroxy-beta-methylbutyrate | |
| CN102138639A (en) | Digestion aiding compound as well as preparation method and application thereof to feed additive | |
| CN103583435B (en) | Eel leucomalachite-green-removal aquaculture method | |
| Metzler-Zebeli et al. | Short-chain fatty acids modulate permeability, motility and gene expression in the porcine fetal jejunum ex vivo | |
| Xiong et al. | Effects of maternal supplementation with rare earth elements during late gestation and lactation on performances, health, and fecal microbiota of the sows and their offspring | |
| CN103990424B (en) | A kind of preparation method of microcapsules of linear dextrin embedding CLA | |
| CN104558624A (en) | Preparation and usage of novel dendrimer | |
| CN105085931A (en) | Novel dendritic macromolecule and its preparation method and use | |
| Khan et al. | Renewable mixed hydrogels based on polysaccharide and protein for release of agrochemicals and soil conditioning | |
| CN105085930A (en) | Novel dendritic macromolecule and its preparation method and use | |
| Pau et al. | Reproductive performance following transcervical insemination with frozen thawed semen in ewes submitted to surgical incision of cervical folds (SICF): Comparison with Laparoscopic Artificial Insemination | |
| Pollard et al. | Supplemental nicotinic acid elevates NAD+ precursors in the follicular fluid of mares | |
| Komane et al. | Atrial Natriuretic Peptide Antibody-Functionalised, PEGylated Multiwalled Carbon Nanotubes for Targeted Ischemic Stroke Intervention | |
| CN104558627A (en) | Novel dendrimer as well as preparation and application thereof | |
| CN102120823B (en) | The synthesis of water solublity zein and the utilization in pharmaceutical preparation | |
| Miró et al. | Specific seminal plasma fractions are responsible for the modulation of sperm–PMN binding in the donkey | |
| He et al. | Heating Drinking Water in Cold Season Improves Growth Performance via Enhancing Antioxidant Capacity and Rumen Fermentation Function of Beef Cattle | |
| CN112618710B (en) | Plant glycogen pig oral vaccination nanometer adjuvant and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150429 |
|
| WD01 | Invention patent application deemed withdrawn after publication |