CN105497055A - Application of nicotinamide adenine dinucleotide in preparation of medicine for preventing and treating skin radiation injury - Google Patents
Application of nicotinamide adenine dinucleotide in preparation of medicine for preventing and treating skin radiation injury Download PDFInfo
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- CN105497055A CN105497055A CN201410493273.4A CN201410493273A CN105497055A CN 105497055 A CN105497055 A CN 105497055A CN 201410493273 A CN201410493273 A CN 201410493273A CN 105497055 A CN105497055 A CN 105497055A
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- nicotinamide adenine
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Abstract
The invention discloses an application of nicotinamide adenine dinucleotide (NAD+) in preparation of a medicine for preventing and treating skin radiation injury. A modern pharmacological test proves that when the NAD+ is used for smearing skin of mice, a significant protective effect of preventing or treating X-ray induced skin injury is achieved, which means that preventive drug delivery can prevent or treat the skin radiation injury.
Description
Technical field
The present invention relates to the application of nicotinamide adenine dinucleotide in pharmaceutical field.More particularly that (nicotinamideadeninedinucleotide is called for short NAD to nicotinamide adenine dinucleotide
+) preparing the application in prevention or treatment radiation injury of skin medicine.
Background technology
The chemical structural formula of nicotinamide adenine dinucleotide is:
The preparation method of nicotinamide adenine dinucleotide is mainly raw material with yeast, and yeast is through boiling water extraction, and lead acetate acid precipitation obtains crude product, through the process of formic acid type cation exchange resin column, refines and obtains.
The present inventor is Late Cambrian in an experiment: nicotinamide adenine dinucleotide has significant protective effect in control radiation injury of skin.The present invention is completed through further experiment based on above-mentioned discovery.
Summary of the invention
Late Cambrian in an experiment: the application of nicotinamide adenine dinucleotide in the skin injury of control X ray induction.This medicine has significant protective effect.
The object of the invention is nicotinamide adenine dinucleotide as the application of active component in preparation prevention or treatment radiation injury of skin.
Further, nicotinamide adenine dinucleotide is as the application of sole active agent in preparation prevention or treatment radiation injury of skin.
Further, its radiation above-mentioned, mainly refers to the electromagnetic radiation of the higher-energy such as X-ray, ultraviolet, gamma-rays.
Further, above-mentioned radiation injury of skin, for skin thickness is thinning, skin follicle sum reduce, the hair follicle number of plies reduce, keratodermatitis paraplasm and Skin Cell increasing apoptosis many.
Further, pharmaceutical dosage form prepared by described nicotinamide adenine dinucleotide is that preparation is smeared in various external, tablet, capsule, granule, drop pill, suspensoid, syrup, various enteric coated preparation or injection.
Accompanying drawing explanation
Fig. 1 skin histology HE dyes, NAD
+, hair follicle total minimizing thinning to the skin thickness of X ray induction, the hair follicle number of plies reduces protective effect.
Fig. 2 skin thickness quantitative statistics, NAD
+protective effect is had to the skin thickness of X ray induction is thinning.
Fig. 3 skin follicle number of plies quantitative statistics, NAD
+the skin follicle number of plies of X ray induction is reduced and has protective effect.
Fig. 4 skin histology HE dyes, NAD
+protective effect is had to the keratodermatitis paraplasm of X ray induction.
Fig. 5 skin histology TUNEL colored graph, NAD
+protective effect is added with to the Skin Cell increasing apoptosis of X ray induction.
Detailed description of the invention
The experiment content of the present invention to the application of nicotinamide adenine dinucleotide in preparation control radiation injury of skin medicine mainly comprises the following aspects:
1.NAD
+the hair follicle sum of X ray induction is reduced and has protective effect.
2.NAD
+protective effect is had to the skin thickness of X ray induction is thinning.
3.NAD
+the skin follicle number of plies of X ray induction is reduced and has protective effect.
4.NAD
+protective effect is had to the keratodermatitis paraplasm of X ray induction.
5.NAD
+the Skin Cell apoptosis (TUNEL signal) of X ray induction is increased and has protective effect.
NAD is further illustrated below by pharmacodynamic experiment
+in control radiation injury of skin, there is obvious therapeutical effect.
One, experimental technique
1, animal operation
Research uses rat, and experimental animal feeding carries out zoopery Shanghai Communications University MED-X academy, and radiation experiments carries out at SSRF, the synchrotron radiation X-ray that radiating light source uses third generation synchrotron radiation light source to produce.All operating processes all meet Shanghai Communications University's laboratory animal protection and use rules.7% chloral hydrate selected by anesthetis, and anesthesia method is lumbar injection, dosage 1mL/100g.Shave hair to rat leg skin after anesthesia, skin surface coating administration, after coating, 30min carries out the irradiation of local synchronization radiation X ray to the leg area of painting medicine.Drug solvent uses glycerol to mix by a certain percentage with deionized water.Matched group smears a certain amount of solvent, and experimental group smears equal-volume 500mMNAD
+solution.After radiation completes, rat is raised in Animal House, and condition is 22-24 DEG C, the light/dark circulation of 12 hours, and can ad lib water intaking.Sacrifice rat after 5 days, get leg skin.
2, the storage of skin histology
After skin takes out, take out appropriate tissue and be soaked in 4% paraformaldehyde, for making paraffin section.Residue tissue aluminium-foil paper wraps, and uses liquid nitrogen freezing, transfers to-80 DEG C of refrigerators afterwards and preserve for a long time.
3, skin histology paraffin section
Skin histology is soaked 4% paraformaldehyde solution 24h, the manufacture method then according to paraffin section soaks tap water, distilled water, graded ethanol, dimethylbenzene, paraffin successively, is made into paraffin section.
4, the HE dyeing of skin paraffin section
Paraffin section is soaked dimethylbenzene dewaxing, be then dipped in graded ethanol, distilled water successively, haematoxylin dyeing 10 minutes, tap water running water 30min, distilled water immersion 30s, 95% ethanol 10s, 30s is redyed in Yihong, 70% ethanol wash 2 times, soaks graded ethanol, dimethylbenzene, resinene mounting successively.Experimental procedure is with reference to green skies company haematoxylin & eosin staining reagents box.
5, skin histology apoptotic signal detects (TUNEL)
With reference to the TUNEL detection kit of Merck Millipore Corp., TUNEL dyeing is carried out to skin paraffin section.
6, coloration result taken pictures, quantize
Above-mentioned two kinds of dyeing are taken pictures.And quantize for indexs such as the hair follicle number of plies, skin thickness.
7, statistical analysis
All data are according to meansigma methods
+the mode of standard deviation provides.Data use one factor analysis of variance to assess, and then use Student-Newman-Keulsposthoctest.P value is less than 0.05 and thinks statistically significant.
Two, experimental result and discussion
1, NAD
+to the total minimizing of the skin follicle of X ray induction, skin thickness minimizing, the minimizing of the hair follicle number of plies, there is protective effect.
Control rats skin application solvent, and x-ray bombardment is carried out to this place's leg skin, radiation dose is 8Gy, finds that skin follicle sum reduces, skin thickness reduces, the hair follicle number of plies reduces, and experimental group rat skin coating equal-volume 500mMNAD
+solution then can effectively stop above-mentioned damage.Representative H & E coloration result is shown in Fig. 1 (50 times of amplifications), and the quantized result of skin thickness, the hair follicle number of plies is shown in Fig. 2, Fig. 3 respectively.
2, NAD
+to the keratodermatitis paraplasm of X ray induction, there is protective action.
Control rats skin application solvent, and x-ray bombardment is carried out to this place's leg skin, radiation dose is 8Gy, finds keratodermatitis paraplasm, and experimental group rat skin coating equal-volume NAD
+solution then effectively can reduce the paraplasm of keratodermatitis.Representative H & E coloration result is shown in Fig. 4 (200 times of amplifications).
3, NAD
+to the Skin Cell apoptosis increase of X ray induction, there is protective effect.
Control rats skin application solvent, and x-ray bombardment is carried out to this place's leg skin, radiation dose is 8Gy, can cause the increase of Skin Cell apoptotic signal, and experimental group rat skin coating equal-volume 500mMNAD
+solution then effectively can reduce the increase of apoptotic signal.TUNEL coloration result is shown in Fig. 5 (amplification of 200 times, first row picture, the amplification of 1000 times, second row picture).
Show according to above result, NAD
+can protect the skin injury of X ray induction, it is thinning that its mark comprises skin thickness, skin follicle sum reduce, the hair follicle number of plies reduce, horny layer paraplasm and Skin Cell increasing apoptosis many.The electromagnetic radiation of higher-energy is as X-ray, ultraviolet, gamma-rays etc., and the mechanism producing radiation injury of skin has some common mechanism, comprises DNA damage and response to oxidative stress, therefore above result prompting NAD
+significant application value is had in preparation control radiation injury of skin medicine.
The good effect that the present invention is compared with prior art had is:
The electromagnetic radiation of higher-energy such as X-ray, ultraviolet, gamma-rays can cause response to oxidative stress and the DNA damage of skin histology, and for these damages, not effective especially means carry out protecting, treating at present.And the present invention can available protecting radiation injury of skin, for making with NAD later
+for the medicine of the anti-radiation injury of skin of main component and with NAD
+the clinical practice of the skin injury caused at prevention, treatment ultraviolet skin injury, x-ray imaging, radiotherapy for the medicine of main component provides important scientific basis.
Claims (6)
1. the application of nicotinamide adenine dinucleotide in preparation control radiation injury of skin medicine, the chemical structural formula of nicotinamide adenine dinucleotide is:
。
2. nicotinamide adenine dinucleotide is as the application of active component in preparation control radiation injury of skin medicine.
3. nicotinamide adenine dinucleotide is as the application of sole active agent in preparation control radiation injury of skin medicine.
4. the application of the nicotinamide adenine dinucleotide according to claim 1 or 2 or 3 in preparation control radiation injury of skin medicine, it is characterized in that, described radiation injury of skin, for skin thickness is thinning, skin follicle sum reduces, the hair follicle number of plies reduce, keratodermatitis paraplasm and Skin Cell increasing apoptosis many.
5. the application of the nicotinamide adenine dinucleotide according to claim 1 or 2 or 3 in preparation control radiation injury of skin medicine, is characterized in that, described radiation, refers to X-ray, ultraviolet or gamma-ray electromagnetic radiation.
6. the application of the nicotinamide adenine dinucleotide according to claim 1 or 2 or 3 in preparation control radiation injury of skin medicine, the pharmaceutical dosage form of described preparation is that preparation, tablet, capsule, granule, drop pill, suspensoid, syrup, enteric coated preparation or injection are smeared in external.
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|---|---|---|---|
| CN201410493273.4A CN105497055B (en) | 2014-09-24 | 2014-09-24 | Nicotinamide adenine dinucleotide is preparing the application in preventing radiation injury of skin medicine |
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| CN105497055B CN105497055B (en) | 2018-05-08 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107362362A (en) * | 2017-07-20 | 2017-11-21 | 复旦大学 | Application of the SIRT1 inhibitor in radioactive intestines problem is prevented and treated |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5250290A (en) * | 1990-10-30 | 1993-10-05 | L'oreal | Cosmetic use of a composition having antierythemal activity and corresponding composition |
| CN103108640A (en) * | 2010-08-10 | 2013-05-15 | 多美化学有限公司 | Pharmaceutical or cosmetic composition containing nicotinic acid adenine dinucleotide phosphate or derivative thereof |
-
2014
- 2014-09-24 CN CN201410493273.4A patent/CN105497055B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5250290A (en) * | 1990-10-30 | 1993-10-05 | L'oreal | Cosmetic use of a composition having antierythemal activity and corresponding composition |
| CN103108640A (en) * | 2010-08-10 | 2013-05-15 | 多美化学有限公司 | Pharmaceutical or cosmetic composition containing nicotinic acid adenine dinucleotide phosphate or derivative thereof |
Non-Patent Citations (2)
| Title |
|---|
| 刘发全: "还原型辅酶NADH抗辐射损伤的实验研究", 《中国优秀博士学位论文全文数据库（医药卫生辑）》 * |
| 陈沅江等: "《职业卫生与防护》", 28 February 2009 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107362362A (en) * | 2017-07-20 | 2017-11-21 | 复旦大学 | Application of the SIRT1 inhibitor in radioactive intestines problem is prevented and treated |
| CN107362362B (en) * | 2017-07-20 | 2019-01-01 | 复旦大学 | SIRT1 inhibitor is preventing and treating the application in radioactive intestines problem |
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| CN105497055B (en) | 2018-05-08 |
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