CN106974905A - A kind of Self-Assembled based on natural drug Puerarin - Google Patents
A kind of Self-Assembled based on natural drug Puerarin Download PDFInfo
- Publication number
- CN106974905A CN106974905A CN201710195885.9A CN201710195885A CN106974905A CN 106974905 A CN106974905 A CN 106974905A CN 201710195885 A CN201710195885 A CN 201710195885A CN 106974905 A CN106974905 A CN 106974905A
- Authority
- CN
- China
- Prior art keywords
- puerarin
- hydrogel
- small molecule
- assembled
- self
- 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
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Hydrogel is filled the present invention relates to a kind of Self-Assembled based on natural drug Puerarin.The composition of the micro-molecular hydrogel comprises only Puerarin, without any chemical modification and auxiliary additive, with production process is simple, cost is low, can slowly discharge Puerarin and improve it is oral under the conditions of Puerarin bioavilability the characteristics of and advantage.In view of Puerarin has anti-peroxidation, protection cell, promotes the effect such as angiogenesis, Puerarin micro-molecular hydrogel of the present invention is with a wide range of applications in fields such as organizational project, ophthalmology disease, wound healings.
Description
Technical field
The present invention relates to a kind of micro-molecular hydrogel formed by natural drug Puerarin, its can long-acting slow-release Puerarin,
And the bioavilability of natural traditional Chinese medicine composition Puerarin can be improved.
Background technology
Micro-molecular hydrogel is a kind of novel hydrogels occurred in recent years, and it passes through non-covalent bond self assembly by small molecule
Form, with biocompatibility it is high, be easy to degrade and absorb the features such as and advantage.Therefore, it cell culture, organizational project,
The fields such as medicine controlled releasing, regenerative medicine have shown splendid application prospect.Micro-molecular hydrogel is mostly by polypeptide, amino acid derived
The small molecules such as thing, compound containing heterocycle are formed by self assembly.Do not deposited however, these compounds are chemical synthesis, nature
.The micro-molecular hydrogel formed by these compounds needs to test by complicated and rigorous experiment in clinical practice application
Demonstrate,prove biocompatibility and bioactivity.This considerably increases complexity, cost and the construction cycle prepared by hydrogel.It is preferable
Micro-molecular hydrogel be preferably that can be used for the compound of human body by being verified to form by self assembly.For example, unique
Ratified for one to be formed by Lanreotide self assembly applied to the micro-molecular hydrogel of medicament slow release by FDA.It is blue before 2009
Auspicious peptide is to inject to treat applied to acromegalia in the way of solution, and intramuscular injection is required for daily once.Later, found
Lanreotide can be self-assembly of the micro-molecular hydrogel of g., jelly-like when improving concentration (when more than 2%), therefore with medicament slow release water
The form of gel novel form obtains FDA approval.Now, Lanreotide hydrogel hypodermic injection once can be 1 with slow releasing pharmaceutical
Month.Therefore, if the hydrogel for having been approved by the small molecule formation applied to human body, this long-acting administration to the medicine can be obtained
It is relevant.
Puerarin is also known as puerarin.It is the isoflavonoid derivatives that there is coronary dilatation to act on separated from Chinese medicament kudzu-vine root.
It is present in the root of legume Pueraria lobota and elegant jessamine.With bringing down a fever, it is calm and make the increased effect of coronary blood flow, after hypophysis
Acute myocardial bleeding has protective effect caused by foline.Clinically it is used for coronary disease and angina pectoris, hypertension.Its structure such as following formula institute
Show：
The content of the invention
Innovation of the present invention is that discovery clinical medicine Puerarin, can induce it certainly by heating the method for cooling
Assembling forms micro-molecular hydrogel.Puerarin in the hydrogel is self-assembly of nanofiber, sustained release Pueraria lobota that can not only be long-acting
Root element medicine, moreover it is possible to improve the bioavilability of Puerarin.
One aspect of the invention provides a kind of Puerarin small molecule Self-Assembled, it is characterised in that by Puerarin certainly
Assembling is made.
In the inventive solutions, it is dissolved in after water-soluble medium by Puerarin is heated to dissolving, then carries out
Cooling is obtained.
In the inventive solutions, the content of Puerarin is 0.8%wt- in Puerarin small molecule Self-Assembled
8%wt, preferably 1%wt-4%wt.
In the inventive solutions, water-soluble medium is the aqueous solution that pH is 6-8, and preferably pH is 6.8-7.4's
PBS solution.
In the inventive solutions, heating-up temperature is 80 DEG C -100 DEG C.
In the inventive solutions, Puerarin small molecule Self-Assembled is in nanometer fibrous.
Another aspect of the invention provides the preparation method of Puerarin small molecule Self-Assembled, and it includes following step
Suddenly：
1) by Puerarin solution in water-soluble medium,
2) heating water-soluble medium extremely dissolves,
3) it is cooled to the Puerarin small molecule Self-Assembled that room temperature is obtained.
In the inventive solutions, water-soluble medium is the aqueous solution that pH is 6-8, and preferably pH is 6.8-7.4's
PBS solution.
In the inventive solutions, heating-up temperature is 80 DEG C -100 DEG C.
Another aspect of the present invention provides medicine of the Puerarin small molecule Self-Assembled in slowly release Puerarin
In purposes or prepare miocardial infarction medicine in purposes.
Inventor has found, Puerarin is scattered in into neutral aqueous medium, by dissolving by heating and then being cooled back to room temperature
Mode can prepare a kind of new micro-molecular hydrogel.
As a result Puerarin is shown under conditions of pH is 6.8-7.4, concentration is more than or equal to 0.8% (mass/volume)
Hydrogel can be formed by heating the method for cooling, the hydrogel of formation is largely all made up of water.
Experiment shows that the root of kudzu vine hydrogel that the present invention is formed forms uniform nanofibrous structures, and can stablize
Slowly discharge medicine.
Experiment shows that gavage gives SD rat 4%wt roots of kudzu vine hydrogel (Puerarin dosage is 400mg/Kg), and Pueraria lobota
Root element monomer suspension (dosage 400mg/Kg), with time lengthening, Puerarin mean blood plasma concentration is in hydrogel group compared with monomer
Suspension group is significantly improved；And the bioavilability of root of kudzu vine hydrogel improves 3 times compared with Puerarin monomer, difference has statistics meaning
Justice.
The preparation method of the root of kudzu vine hydrogel is comprised the steps of：
(1) Puerarin is scattered in neutral aqueous medium with 0.8% to 8% concentration.
(2) 80 DEG C -100 DEG C are heated to so that Puerarin is completely dissolved, water-setting can be formed by being cooled to 2-5 minutes after room temperature
Glue.
The beneficial effects of the invention are as follows：
The first Self-Assembled based on natural drug of 1 invention nature in itself.
2 provide a kind of new small molecule hydrogel material, can be sustained Puerarin medicine and improve its bioavilability.
3 hydrogels have high application prospect in fields such as medicament slow release, heart infarction treatments
Brief description of the drawings
Fig. 1：The hydrogel that Puerarin is formed in the PBS aqueous solution；
Fig. 2：With the nanofibrous structures inside transmission electron microscope observation root of kudzu vine hydrogel；
Fig. 3：1%th, 2%, the root of kudzu vine hydrogel under 4% 3 kind of concentration discharge in vitro Puerarin medicine release it is bent
Line.
Embodiment
Embodiment 1：The preparation 1 of root of kudzu vine hydrogel
10.0mg Puerarins are weighed, PBS (phosphate buffer, pH is 6.8-7.4) 1mL is added, makes Puerarin in PBS
Concentration be 1%wt, alcolhol burner is heated to 80 DEG C -100 DEG C so that Puerarin is completely dissolved, after naturally cooling to room temperature 5 minutes,
The micro-molecular hydrogel of jelly sample can be formed.
Embodiment 2：The preparation 2 of root of kudzu vine hydrogel
20.0mg Puerarins are weighed, PBS (phosphate buffer, pH is 6.8-7.4) 1mL is added, makes Puerarin in PBS
Concentration be 2%wt, alcolhol burner is heated to 80 DEG C -100 DEG C so that Puerarin is completely dissolved, after naturally cooling to room temperature 5 minutes,
The micro-molecular hydrogel of jelly sample can be formed.
Embodiment 3：The preparation 3 of root of kudzu vine hydrogel
40.0mg Puerarins are weighed, PBS (phosphate buffer, pH is 6.8-7.4) 1mL is added, makes Puerarin in PBS
Concentration be 4%wt, alcolhol burner is heated to 80 DEG C -100 DEG C so that Puerarin is completely dissolved, after naturally cooling to room temperature 5 minutes,
The micro-molecular hydrogel of jelly sample can be formed.
Embodiment 4：The nanofiber of root of kudzu vine hydrogel is characterized
Prepared by above-described embodiment 1-3 after Puerarin micro-molecular hydrogel, it is left to draw about 15 μ L with liquid-transfering gun
Right hydrogel is added drop-wise on copper mesh, hydrogel is evenly applied to copper mesh surface with nitrogen treatment.Copper mesh is quiet in drier
Put after being dried overnight, use the appearance of nano material (such as Fig. 2) observed under transmission electron microscope in hydrogel.Experiment shows,
The root of kudzu vine hydrogel that the present invention is formed forms uniform nanofibrous structures, and stably can slowly discharge medicine.
Embodiment 5：The vitro drug release of root of kudzu vine hydrogel
Each 200ul of root of kudzu vine hydrogel of method described above preparation 1%, 2% and 4% adds 250ul's in bottle
PBS.200ul supernatants are taken out in the 1st, 2,4,6,8,10 and 12 hour each time point, the fresh PBS of 200ul are added, will
The solution that each time point takes out carries out LC-MS chromatography.Calculated by peak area untill Puerarin appearance on chromatogram
The cumulative release percentage of Puerarin, data analysis and chart production are carried out with the softwares of OriginPro 9.0.Experimental result referring to
Accompanying drawing 3
Embodiment 6：Determination of drug concentration when root of kudzu vine hydrogel is administered orally in blood
(a) animal administration and blood sampling:Male rat 10, SPF grades of environmental suitabilities are raised, and after one week, are randomly divided into 2
Group, every group 5.Fasting 12h, free water before all rat administrations.After weighing, it is grouped at random by body weight, one group is Puerarin
Monomer suspension solution group, one group is 4wt% root of kudzu vine hydrogel groups.Puerarin monomer suspension solution collocation method：First configure
0.5% carboxymethylcellulose sodium solution, stand-by after cooling, then precision weighing Puerarin powder, takes in a small amount of addition mortar, together
When add a small amount of 0.5% carboxymethylcellulose sodium solution, slowly grind, by several times complete grinding until formed Puerarin suspension,
In uniform milky.Two groups are pressed 400mg/kg gastric infusions respectively.After administration respectively at 0,5,10,15,30,60,90,120,
180th, 240,360,480,600min is taken a blood sample through orbital venous plexus, and blood about 0.5mL is taken every time, 2 hours after administration, is mended in taking after blood
Fill normal saline.Whole blood 8000rpm centrifuges 6min, takes supernatant, -20 DEG C of preservations of blood plasma；(b) pharmacokinetic parameters are calculated:Blood
Drug concentration-versus-time data are starched to handle using the softwares of DAS 2.0 (Chinese Mathematics pharmacology Professional Committee, Chinese Shanghai).Using
Two compartment model calculates the pharmacokinetic parameters such as AUC, CLz/F, t1/2, Cmax and Tmax.Root of kudzu vine hydrogel and Puerarin bulk drug
Bioequivalence analysis, carry out statistical analysis using SPSS softwares, the comparisons of two groups of means is using independent samples t test point
Analysis.Experimental result is referring to Tables 1 and 2.
After the gastric infusion root of kudzu vine hydrogel of table 1 in rat body Puerarin blood concentration
Puerarin pharmacokinetic parameter in rat body after the gastric infusion of table 2
Conclusion：The bioavilability of root of kudzu vine hydrogel improves 3 times compared with Puerarin monomer, and difference has statistics
Experiment shows that gavage gives SD rat 4%wt roots of kudzu vine hydrogel (Puerarin dosage is 400mg/Kg), and Pueraria lobota
Root element monomer suspension (dosage 400mg/Kg), with time lengthening, Puerarin mean blood plasma concentration is in hydrogel group compared with monomer
Suspension group is significantly improved；And the bioavilability of root of kudzu vine hydrogel improves 3 times compared with Puerarin monomer, difference has statistics meaning
Justice.
Claims (10)
1. a kind of Puerarin small molecule Self-Assembled, it is characterised in that be made up of Puerarin self assembly.
2. Puerarin small molecule Self-Assembled as claimed in claim 1, it is characterised in that it is dissolved in water by Puerarin
Dissolving is heated to after dissolubility medium, cooling acquisition is then carried out.
3. Puerarin small molecule Self-Assembled as claimed in claim 2, it is characterised in that Puerarin small molecule self assembly
The content of Puerarin is 0.8%wt-8%wt, preferably 1%wt-4%wt in hydrogel.
4. Puerarin small molecule Self-Assembled as claimed in claim 2, it is characterised in that water-soluble medium is that pH is 6-
8 aqueous solution, preferably pH are 6.8-7.4 PBS solution.
5. Puerarin small molecule Self-Assembled as claimed in claim 2, it is characterised in that heating-up temperature is 80 DEG C -100
℃。
6. Puerarin small molecule Self-Assembled as claimed in claim 2, it is characterised in that Puerarin small molecule self assembly
Hydrogel is in nanometer fibrous.
7. the preparation method of the Puerarin small molecule Self-Assembled as described in claim any one of 1-6, it includes as follows
Step：
1) by Puerarin solution in water-soluble medium,
2) heating water-soluble medium extremely dissolves,
3) it is cooled to the Puerarin small molecule Self-Assembled that room temperature is obtained.
8. preparation method according to claim 7, wherein, water-soluble medium is the aqueous solution that pH is 6-8, and preferably pH is
6.8-7.4 PBS solution.
9. preparation method according to claim 7, heating-up temperature is 80 DEG C -100 DEG C.
10. the Puerarin small molecule Self-Assembled as described in claim any one of 1-6 is slowly discharging the medicine of Puerarin
Purposes in thing or the purposes in the medicine for preparing miocardial infarction.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710195885.9A CN106974905A (en) | 2017-03-29 | 2017-03-29 | A kind of Self-Assembled based on natural drug Puerarin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710195885.9A CN106974905A (en) | 2017-03-29 | 2017-03-29 | A kind of Self-Assembled based on natural drug Puerarin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106974905A true CN106974905A (en) | 2017-07-25 |
Family
ID=59339278
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710195885.9A Pending CN106974905A (en) | 2017-03-29 | 2017-03-29 | A kind of Self-Assembled based on natural drug Puerarin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106974905A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110665052A (en) * | 2019-10-24 | 2020-01-10 | 上饶师范学院 | Puerarin hydrogel wound auxiliary material |
| CN112569180A (en) * | 2020-12-30 | 2021-03-30 | 长安大学 | Mangiferin small-molecule hydrogel and preparation method and application thereof |
| CN115429929A (en) * | 2021-06-04 | 2022-12-06 | 中国科学院上海硅酸盐研究所 | Injectable self-assembled hydrogel and preparation method and application thereof |
| KR102669861B1 (en) | 2020-04-23 | 2024-05-28 | 동국대학교 와이즈캠퍼스 산학협력단 | Composition Comprising Puerarin for Wound Healing |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101006988A (en) * | 2005-09-26 | 2007-08-01 | 刘凤鸣 | Slow release preparation of puerarin |
-
2017
- 2017-03-29 CN CN201710195885.9A patent/CN106974905A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101006988A (en) * | 2005-09-26 | 2007-08-01 | 刘凤鸣 | Slow release preparation of puerarin |
Non-Patent Citations (1)
| Title |
|---|
| 张建武: "葛根素水凝胶在MSCs移植治疗心肌梗死中的作用及机制研究", 《中国博士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110665052A (en) * | 2019-10-24 | 2020-01-10 | 上饶师范学院 | Puerarin hydrogel wound auxiliary material |
| KR102669861B1 (en) | 2020-04-23 | 2024-05-28 | 동국대학교 와이즈캠퍼스 산학협력단 | Composition Comprising Puerarin for Wound Healing |
| CN112569180A (en) * | 2020-12-30 | 2021-03-30 | 长安大学 | Mangiferin small-molecule hydrogel and preparation method and application thereof |
| CN112569180B (en) * | 2020-12-30 | 2023-06-02 | 长安大学 | Mangiferin small-molecule hydrogel and preparation method and application thereof |
| CN115429929A (en) * | 2021-06-04 | 2022-12-06 | 中国科学院上海硅酸盐研究所 | Injectable self-assembled hydrogel and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Tian et al. | The development of low-molecular weight hydrogels for applications in cancer therapy | |
| Wan et al. | Structure‐guided engineering of cytotoxic cabazitaxel for an adaptive nanoparticle formulation: Enhancing the drug safety and therapeutic efficacy | |
| JP5369332B2 (en) | Pharmaceutical composition containing docetaxel having stability, and method for producing the same | |
| CN106974905A (en) | A kind of Self-Assembled based on natural drug Puerarin | |
| CN106916177B (en) | A kind of deuterated dipeptide boronic acid or its ester type compound and its synthetic method and purposes | |
| CN108379549B (en) | Preparation method and application of anti-cancer supramolecular hydrogel containing casein valine peptide and based on D-configuration short peptide self-assembly | |
| CN103228676B (en) | Hydroxy alkyl cellulose | |
| WO2018010571A1 (en) | Injectable pharmaceutical composition of tecovirimat and preparation method thereof | |
| CN102228430A (en) | Nano-suspension for silybin-phospholipid complex and preparation method thereof | |
| CN113004536A (en) | Metal-amino acid/peptide coordination polymer and application thereof | |
| WO2001079302A1 (en) | A complex between folic acid and polysaccharides, its preparation method and a pharmaceutical composition comprising said complex as active component | |
| CN105148289B (en) | A kind of amphipathic oligomerised polypeptides drug conjugates | |
| CN108517003B (en) | The plastic factor, hydrogel and pharmaceutical composition | |
| CN103980717B (en) | The modified capsule of a kind of gelatin cross-blend natural polysaccharide | |
| CN109394692A (en) | Dasatinib Graft copolymer micella, its freeze drying powder injection and preparation method and application | |
| CN1823748B (en) | Medicinal preparation of coenzyme Q10 liposome and its preparation technology | |
| CN107496362A (en) | A kind of Vonoprazan fumarate solid dispersions and preparation method thereof | |
| CN104688705B (en) | A kind of alpha lipoic acid sustained release tablets and preparation method thereof | |
| CN115073552B (en) | Polypeptide, hydrogel and application thereof | |
| CN102133200B (en) | Human relaxin-2 lyophilized powder preparation for injection | |
| CN101897978A (en) | Method for preparing medicinal biological material | |
| CN110559204B (en) | 5-aminolevulinic acid hydrogel composition and preparation method and application thereof | |
| CN111467473A (en) | Polypeptide HM-3 nano-particles and preparation method thereof | |
| CN106074438A (en) | A kind of starch matrix Capsules comprising nonspecific immunity strengthening agent | |
| CN108358995B (en) | CP-iRGD polypeptide, iDPP nanoparticle, drug-loaded compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170725 |
|
| RJ01 | Rejection of invention patent application after publication |