CN109985057A - Purposes of the tetrahedral framework nucleic acid in the drug of preparation skin repair - Google Patents
Purposes of the tetrahedral framework nucleic acid in the drug of preparation skin repair Download PDFInfo
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- CN109985057A CN109985057A CN201910302857.1A CN201910302857A CN109985057A CN 109985057 A CN109985057 A CN 109985057A CN 201910302857 A CN201910302857 A CN 201910302857A CN 109985057 A CN109985057 A CN 109985057A
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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
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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Abstract
The present invention relates to the purposes of drug field more particularly to tetrahedral framework nucleic acid in the drug of preparation skin repair.The present invention provides purposes of the tetrahedral framework nucleic acid in preparation skin repair drug, the tetrahedral framework nucleic acid be it is single-stranded after 80 DEG C of temperatures above are denaturalized by 4 DNA, in the tetrahedral structure that 10 DEG C of following temperature renaturation obtain；In the tetrahedral structure, the amount of four DNA single-stranded substance is consistent.The present invention can effectively repair damaged skin, reduce inflammatory reaction, reduce scar and generate, have a good application prospect.
Description
Technical field
The present invention relates to the use of drug field more particularly to tetrahedral framework nucleic acid in the drug of preparation skin repair
On the way.
Background technique
First barrier of the skin as human body, is often most subject to the destruction of the factors such as biology, physics, chemistry, causes
Defect, and defect of skin not only results in inflammation, scar, influences function, the appearance of patient, it is also possible to cause a series of psychological diseases
Disease.Promoting defect of skin healing is always one of the emphasis of surgeon's research.
The prior art for the treatment of defect of skin has gene therapy, stem cell therapy, excretion autogenic therapy etc. at present.Gene therapy
Mainly rely on viral vectors or non-virus carrier, the transcription growth factor class cDNA in skin histology, required for generating
Growth factor, to realize the healing for promoting defect of skin.Stem cell therapy is to be inoculated with separate sources at defect of skin position
Stem cell accelerates defect of skin healing by promoting stem cells hyperplasia, migration and differentiation to reach.Excretion autogenic therapy is to collect
The excretion body that normal epithelium cell generates, is seeded at defect of skin, by the cell factor contained in excretion body, to promote skin
The healing of skin defect.
Gene therapy, excretion autogenic therapy, stem cell therapy are required to largely use material requested, however can be lacked by skin
The material utilized at damage is seldom, and under efficiency is very low, patient is difficult to be resistant to.Prior art production process is complicated, time-consuming and laborious, produces
Object purity is not also high.In addition, the prior art promotes defect of skin healing effect also not satisfactory, the effect for reducing scar is limited.
Tetrahedral framework nucleic acid is that one kind is single-stranded after 80 DEG C of temperatures above are denaturalized by 4 DNA, multiple in 10 DEG C of following temperature
The nucleic acid product with tetrahedral configuration space structure that property obtains.Tetrahedral framework nucleic acid is often used as pharmaceutical carrier；Mesh
It is preceding there is not yet the report applied in skin repair in relation to tetrahedral framework nucleic acid.
Summary of the invention
It is an object of the invention to: application of the tetrahedral framework nucleic acid in skin repair is provided.
Technical scheme is as follows:
Purposes of the tetrahedral framework nucleic acid in preparation skin repair drug.
Purposes as the aforementioned, the drug are the drugs for reducing cicatrix of skin.
Purposes as the aforementioned, the drug are the drugs for repairing skin mechanical damage.
Purposes as the aforementioned, the drug are the drugs for promoting migration of fibroblast cells.
Purposes as the aforementioned, the drug are the drugs for promoting keratinocyte migration.
Purposes as the aforementioned, the tetrahedral framework nucleic acid are mono- as sequence four DNA as shown in NO.1~4 SEQ ID
Chain is constituted.
A kind of skin repair drug, it is using tetrahedral framework nucleic acid as active constituent, in addition pharmaceutically acceptable auxiliary
Helping property ingredient is prepared.
Drug as the aforementioned, the drug are the drugs for reducing cicatrix of skin, the drug for repairing skin mechanical damage, promote
The drug of migration of fibroblast cells and/or the drug for promoting keratinocyte migration.
Drug as the aforementioned, the tetrahedral framework nucleic acid are mono- as sequence four DNA as shown in NO.1~4 SEQ ID
Chain is constituted.
Drug as the aforementioned, the drug are ejection preparation.
The invention has the following advantages:
1) tetrahedral framework nucleic acid can be reduced the inflammatory reaction of skin wound.
2) tetrahedral framework nucleic acid can promote keratinocyte and fibroblastic migration.
3) tetrahedral framework nucleic acid can promote skin healing, reduce scar and generate.
Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
Above content of the invention is described in further detail again below by way of specific embodiment.But it should not be by this
The range for being interpreted as the above-mentioned theme of the present invention is only limitted to example below.All technologies realized based on above content of the present invention are equal
Belong to the scope of the present invention.
Detailed description of the invention
Fig. 1 is tetrahedral framework nucleic acid and its single-stranded electrophoretogram.
Fig. 2 is the outside drawing of tetrahedral framework nucleic acid under transmission electron microscope.
Fig. 3 is the outside drawing of animal skin defect repair experiment.
Fig. 4 is that the 14th day skin epidermis holostrome sample is substantially seen.
Fig. 5 is the H&E colored graph of the 14th day field of operation epithelium holostrome.
Fig. 6 is keratinocyte scratch experiment figure.
Fig. 7 is fibroblast scratch experiment figure.
Specific embodiment
The synthesis and identification of 1 tetrahedral framework nucleic acid of embodiment
1. synthetic method
Four DNA single-stranded (S1, S2, S3, S4) are dissolved in TM Buffer (10mM Tris-HCl, 50mM MgCl2, pH
=8.0) in, four DNA single-stranded final concentration of 1000nM is sufficiently mixed, and is heated rapidly to 95 DEG C and is kept for 10 minutes, Zhi Houxun
Speed is cooled to 4 DEG C and maintenance 20 minutes or more, and tetrahedral framework nucleic acid can be obtained.
Four single-stranded sequences (5 ' → 3 ') are as follows:
S1:ATTTATCACCCGCCATAGTAGACGTATCACCAGGCAGTTGA
GACGAACATTCCTAAGTCTGAA(SEQ ID NO.1)
S2:ACATGCGAGGGTCCAATACCGACGATTACAGCTTGCTACAC
GATTCAGACTTAGGAATGTTCG(SEQ ID NO.2)
S3:ACTACTATGGCGGGTGATAAAACGTGTAGCAAGCTGTAATC
GACGGGAAGAGCATGCCCATCC(SEQ ID NO.3)
S4:ACGGTATTGGACCCTCGCATGACTCAACTGCCTGGTGATAC
GAGGATGGGCATGCTCTTCCCG(SEQ ID NO.4)
2. identification
Tetrahedral framework nucleic acid after synthesis, the visible tetrahedral framework nucleic acid size of Capillary Electrophoresis is about 180KD, can be recognized
Successfully (Fig. 1) is synthesized for tetrahedral framework nucleic acid.Using transmission electron microscope observing, the tetrahedral structure of visible features (is schemed under mirror
2)。
2 defect of skin reparation of embodiment
1. animal pattern
SD rat totally 5, after the preserved skin of back, the round epithelium of diameter 1em is respectively taken in left and right back with skin puncher
Holostrome.
2. packet transaction
SD rat takes autologous control, and left side is control group, and right side is experimental group.Extremely postoperative 7th day after operation, control group
Physiological saline 0.1ml is subcutaneously injected in art area daily in wound, and tetrahedral framework core is subcutaneously injected in art area daily in experimental group wound
Acid (being dissolved in physiological saline) 0.1ml, tetrahedral framework nucleic acid concentration are 125nM.
3. cosmetic variation and index of correlation testing result
Took pictures in the 0th, 3,7,14 day and record wound area, calculate Wound healing rate=(1- take pictures same day wound area/
Postoperative instant wound area) * 100%.After 14th day takes pictures, animal is put to death, and take 1cm diameter art area epithelium holostrome, production mark
This, row H&E is dyed, intradermal inflammatory infiltration situation and collagen formational situation in observation.
It is found in control group to compare, experimental group was obviously accelerated in wound healing in the 3rd, 7,14 day, and wound area is compared with control group
Obviously become smaller (Fig. 3).Substantially to generate scar more substantially reduced than control group (Fig. 4 is right) for (Fig. 4 is left) wound as it can be seen that experimental group for photo,
Cicatricial tissue is obviously reduced.As it can be seen that control group inflammatory cell infiltrates extensively, skin texture is disorganized (Fig. 5 is left) for HE dyeing, and
Experimental group inflammatory reaction is lighter, skin texture ordered arrangement (Fig. 5 is right).It is considered that tetrahedral framework nucleic acid can promote skin
Wound healing reduces scar.
3 cell scratch experiment of embodiment
Keratinocyte, fibroblast are inoculated in 6 orifice plates (30000/hole) overnight respectively, used within second day
Yellow rifle point (the rifle point for the liquid-transfering gun that 200 microlitres of range) is rinsed 3 times with PBS in vertical score in hole, fresh low blood is added afterwards
Clear culture medium (1% serum), is grouped into control group (no tetrahedron), 125nM tetrahedron group, 250nM tetrahedron group, in 0,6,
Time point takes pictures cell migration situation at scratch for 24 hours.
As it can be seen that compared with the control group, 125nM concentration tetrahedron group keratinocyte (Fig. 5) and fibroblast (Fig. 6)
Scratch at area be obviously reduced, cell migration is obviously reinforced.It is considered that tetrahedron can promote keratinocyte and at
The migration of fibrocyte.
SEQUENCE LISTING
<110>Sichuan University
<120>purposes of the tetrahedral framework nucleic acid in the drug of preparation skin repair
<130> GYKH1118-2019P015404CC
<160> 4
<170> PatentIn version 3.5
<210> 1
<211> 63
<212> DNA
<213>artificial sequence
<400> 1
atttatcacc cgccatagta gacgtatcac caggcagttg agacgaacat tcctaagtct 60
gaa 63
<210> 2
<211> 63
<212> DNA
<213>artificial sequence
<400> 2
acatgcgagg gtccaatacc gacgattaca gcttgctaca cgattcagac ttaggaatgt 60
tcg 63
<210> 3
<211> 63
<212> DNA
<213>artificial sequence
<400> 3
actactatgg cgggtgataa aacgtgtagc aagctgtaat cgacgggaag agcatgccca 60
tcc 63
<210> 4
<211> 63
<212> DNA
<213>artificial sequence
<400> 4
acggtattgg accctcgcat gactcaactg cctggtgata cgaggatggg catgctcttc 60
ccg 63
Claims (10)
1. purposes of the tetrahedral framework nucleic acid in preparation skin repair drug.
2. purposes as described in claim 1, the drug is the drug for reducing cicatrix of skin.
3. purposes as described in claim 1, the drug is the drug for repairing skin mechanical damage.
4. purposes as described in claim 1, the drug is the drug for promoting migration of fibroblast cells.
5. purposes as described in claim 1, the drug is the drug for promoting keratinocyte migration.
6. purposes as described in claim 1, it is characterised in that: the tetrahedral framework nucleic acid is by sequence such as SEQ ID NO.1
Four single-stranded compositions of DNA shown in~4.
7. a kind of skin repair drug, which is characterized in that it is using tetrahedral framework nucleic acid as active constituent, in addition pharmaceutically may be used
What the complementary ingredient received was prepared.
8. drug as claimed in claim 7, which is characterized in that the drug is the drug for reducing cicatrix of skin, repairs skin
The drug of mechanical damage, the drug for promoting migration of fibroblast cells and/or the drug for promoting keratinocyte migration.
9. drug as claimed in claim 7, which is characterized in that the tetrahedral framework nucleic acid is by sequence such as SEQ ID NO.1
Four single-stranded compositions of DNA shown in~4.
10. the drug as described in claim 7~9 is any, which is characterized in that the drug is ejection preparation.
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| CN201910302857.1A CN109985057B (en) | 2019-04-15 | 2019-04-15 | Use of tetrahedral skeleton nucleic acid in preparing medicine for repairing skin |
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| CN201910302857.1A CN109985057B (en) | 2019-04-15 | 2019-04-15 | Use of tetrahedral skeleton nucleic acid in preparing medicine for repairing skin |
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| CN109985057A true CN109985057A (en) | 2019-07-09 |
| CN109985057B CN109985057B (en) | 2021-03-12 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112587544A (en) * | 2020-04-28 | 2021-04-02 | 四川大学 | Use of DNA tetrahedral frame nucleic acid in preparing medicine for treating fibrosis disease |
| CN113736776A (en) * | 2021-09-03 | 2021-12-03 | 四川大学 | MicroRNA nano complex based on framework nucleic acid material and preparation method and application thereof |
| CN114569628A (en) * | 2022-03-11 | 2022-06-03 | 四川大学 | Use of DNA tetrahedral framework nano-nucleic acid in cosmetology |
| CN114767830A (en) * | 2022-04-28 | 2022-07-22 | 四川大学 | Compound for preventing osteonecrosis and/or promoting angiogenesis and pharmaceutical application thereof |
| CN114984032A (en) * | 2022-06-27 | 2022-09-02 | 四川大学 | DNA tetrahedral frame nucleic acid-chlorogenic acid compound and application thereof in preparation of medicine for treating hepatic fibrosis |
| CN115192725A (en) * | 2021-04-12 | 2022-10-18 | 四川大学 | Medicine for treating cerebral hemorrhage |
| CN116459271A (en) * | 2023-04-25 | 2023-07-21 | 四川大学 | Use of DNA tetrahedron in preparation of medicine for preventing and/or treating alopecia |
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| CN107286677A (en) * | 2017-08-04 | 2017-10-24 | 广西嘉盈生物科技有限公司 | It is a kind of to induce protein peptides cross linking membrane of epithelial tissue differentiation and preparation method thereof |
| CN108546730A (en) * | 2018-04-19 | 2018-09-18 | 四川大学 | Application of the DNA tetrahedrons in promoting mouse neural stem cells migration |
| CN108586575A (en) * | 2018-04-11 | 2018-09-28 | 福建省中科生物股份有限公司 | A kind of application of polypeptide and its skin repair function |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112587544A (en) * | 2020-04-28 | 2021-04-02 | 四川大学 | Use of DNA tetrahedral frame nucleic acid in preparing medicine for treating fibrosis disease |
| CN115192725A (en) * | 2021-04-12 | 2022-10-18 | 四川大学 | Medicine for treating cerebral hemorrhage |
| CN115192725B (en) * | 2021-04-12 | 2023-05-23 | 四川大学 | Medicine for treating cerebral hemorrhage |
| CN113736776A (en) * | 2021-09-03 | 2021-12-03 | 四川大学 | MicroRNA nano complex based on framework nucleic acid material and preparation method and application thereof |
| CN114569628A (en) * | 2022-03-11 | 2022-06-03 | 四川大学 | Use of DNA tetrahedral framework nano-nucleic acid in cosmetology |
| CN114767830A (en) * | 2022-04-28 | 2022-07-22 | 四川大学 | Compound for preventing osteonecrosis and/or promoting angiogenesis and pharmaceutical application thereof |
| CN114984032A (en) * | 2022-06-27 | 2022-09-02 | 四川大学 | DNA tetrahedral frame nucleic acid-chlorogenic acid compound and application thereof in preparation of medicine for treating hepatic fibrosis |
| CN114984032B (en) * | 2022-06-27 | 2023-07-07 | 四川大学 | DNA tetrahedron framework nucleic acid-chlorogenic acid complex and application thereof in preparation of medicines for treating hepatic fibrosis |
| CN116459271A (en) * | 2023-04-25 | 2023-07-21 | 四川大学 | Use of DNA tetrahedron in preparation of medicine for preventing and/or treating alopecia |
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