CN107126413B - Medicine for treating diabetic ulcer - Google Patents
Medicine for treating diabetic ulcer Download PDFInfo
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- CN107126413B CN107126413B CN201710335648.8A CN201710335648A CN107126413B CN 107126413 B CN107126413 B CN 107126413B CN 201710335648 A CN201710335648 A CN 201710335648A CN 107126413 B CN107126413 B CN 107126413B
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- cinnamaldehyde
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- diabetic ulcer
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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
- A61K31/11—Aldehydes
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- 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
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Abstract
The invention discloses a medicine for treating diabetic ulcer, which is prepared from the following components in parts by weight: cinnamaldehyde and solvent: PEG400, wherein the concentration of cinnamaldehyde in the composition is in the range of 1.2 to 20. mu. mol/L. The medicine for treating the diabetic ulcer is applied to the wound part during treatment, can obviously improve the healing of the diabetic wound, and has good treatment effect and safe and convenient use.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to an external medicine for treating ulcer.
Background
Chronic skin ulcer is not healed for a long time and finally leads to amputation, which is the most main reason for causing disability in diabetes and needs to be researched and solved urgently. CA, a main component of the organic extract in cinnamon, is not only an α, β -unsaturated aldehyde compound approved by FDA for use in food (21CFR § 182.60), but also a use instruction of "generally recognized as safe" given by the american association of perfumers and extracts manufacturers (FEMA) (No. 2286). In addition, a large number of human body researches record the characteristics of systemic pharmacokinetics and safety of the application of the compound, and the compound is prompted to have wide potential clinical application prospects.
Clinical studies at present prove that the oxidative stress injury of the skin at the diabetic ulcer part is serious; recent experiments find that CA can promote the migration of human skin keratinocytes and fibroblasts, reduce the accumulation of ROS in cells, and relieve oxidative stress injury; animal experiments also further prove that Cinnamaldehyde (CA), a specific agonist of Nrf2, can obviously relieve oxidative stress injury and promote wound healing of diabetic ulcer mice. However, the current strategy for applying the Nrf2 agonist is not safe and convenient, and the application modes are generally two, such as intraperitoneal injection of corn oil (mice) containing CA, or addition of 0.1% or 0.5% CA in the diet, but the application modes are not the optimal application modes for clinical diabetic ulcer treatment, and the safety and the convenience are poor.
Therefore, there is a need to find a better application strategy for CA in the treatment of diabetic ulcers.
Disclosure of Invention
In view of the above, the present invention aims to provide a safe and local drug for treating diabetic ulcer, so as to solve the problem that the current application strategy of Nrf2 agonist-CA in diabetic ulcer is not safe and simple.
The invention relates to a medicine for treating diabetic ulcer, which comprises the following components: cinnamaldehyde and solvent: PEG400, wherein the concentration of cinnamaldehyde in the composition is in the range of 1.2 to 20. mu. mol/L.
Preferably, the concentration of cinnamaldehyde in the composition is 4 μmol/L.
The invention has the beneficial effects that:
the medicine for treating the diabetic ulcer is applied to the wound part during treatment, can obviously improve the healing of the diabetic wound, and has good treatment effect and safe and convenient use.
Drawings
FIG. 1 is a graph of wound healing area as a function of time;
FIG. 2 is a graph of quantitative wound healing area as a function of time;
fig. 3 is a diagram of wound tissue healing morphology.
Detailed Description
The invention is further described below with reference to the figures and examples.
The medicine for treating the diabetic ulcer comprises the following components in percentage by weight: cinnamaldehyde and solvent: PEG400, wherein the concentration of cinnamaldehyde in the composition is in the range of 1.2 to 20. mu. mol/L.
The following will describe the preparation method of the present example of the drug for treating diabetic ulcer, taking 1mL of the cinnamaldehyde composition of 4 μmol/L as an example, and the specific steps are as follows:
the method comprises the following steps: preparation of 1mL of a 20mmol/L cinnamic aldehyde composition
1) Mole number of CA contained in 1mL of 20mmol/L cinnamaldehyde composition:
2)n＝c×v
nCA＝(20mmol/L)×(1mL)＝20×10-6mol
3)m＝n×M
mCA＝(20×10-6mol)×132.16＝2.6432×10-3g
4)v＝m/ρ
vCA＝(2.6432×10-3g)÷(1.05g/mL)＝2.517ul
2.517ul CA is added into 1mL PEG400, and then the mixture is shaken at high speed to evenly disperse the CA in the PEG400, thus obtaining 1mL of 20mmol/L cinnamaldehyde composition.
Step two: preparation of 1mL of a 100. mu. mol/L cinnamic aldehyde composition
1) Molar number of CA contained in 1mL of 100. mu. mol/L cinnamaldehyde composition:
n＝c×v
nCA＝(100μmol/L)×(1mL)＝0.1μmol
2) the desired volume of 20mmol/L cinnamaldehyde composition
C1V1＝nCA
V1＝nCA/C1
V1＝0.1μmol/20mmol/L＝5ul
Adding 5ul of the 20mmol/L cinnamaldehyde composition prepared in the step one) into 1mL of PEG400, and uniformly dispersing CA in the PEG400 by high-speed oscillation to obtain 1mL of 100 mu mol/L cinnamaldehyde composition.
Step three: preparation of 1mL of a 4. mu. mol/L cinnamic aldehyde composition
1) Moles of CA contained in 1mL of a 4. mu. mol/L cinnamaldehyde composition:
n＝c×v
nCA＝(4μmol/L)×(1mL)＝0.004μmol
2) the required volume of 100. mu. mol/L cinnamaldehyde composition
C2V2＝nCA
V2＝nCA/C1
V2＝0.004μmol/100μmol/L＝40ul
Adding 40ul of the 100 mu mol/L cinnamaldehyde composition prepared in the second step) into 1mL of PEG400, and then uniformly dispersing CA in the PEG400 by high-speed oscillation to obtain 1mL of a 4 mu mol/L cinnamaldehyde composition which is a light yellow water composition, generally stored in an environment of 4-20 ℃ and can be stably stored for one week.
The following is an experiment that the medicine for treating diabetic ulcer can significantly promote the healing of diabetic wounds by local application:
8 SKH-1 mice aged 8 weeks were intraperitoneally injected with 50mg/kg STZ for 5 days to establish a diabetic mouse model. The group of diabetes and the group of diabetes + CA are respectively divided randomly by adopting a random digital table method. Wound surgery was performed on week 4 after STZ injection and a full skin incision of 6mm diameter was made in the back of the mice. The diabetic + CA group was topically applied with 20 μ L of polyvinyl alcohol 400 (PEG 400) containing 4 μmol/L CA, and the diabetic group used an equal amount of PEG400 for topical application as a control, and skin at the wound margin was collected every 1 day until wound healing day 14. The healing rate was assessed by monitoring the area of skin wound healing every 1 day for 2 weeks post-surgery.
As shown in fig. 1: the change of the wound healing area of the diabetes + CA group at each time point in the diabetes group and the CA group is observed in real time, so that the wound healing condition of the mice in the diabetes + CA group is obviously improved compared with that in the diabetes group. By quantitatively analyzing the change in wound healing area at each time point (as shown in fig. 2), the wound healing rate was significantly increased after 9 days of wound healing (n-8, P < 0.05) by topical application of the inventive drug. Further comparing the difference of wound healing of each group, histologically observing the histomorphological change of the wound of each group at day 14, as shown in fig. 3, it was found that the wound of the diabetic group still had loose granulation tissue and the neoepithelium did not completely cover the wound, however, the neoepithelium was completely formed at the wound of the diabetic group + CA group and the histology was complete. The results show that the local application of the medicine for treating diabetic ulcer can obviously improve the healing of the wound of a diabetic mouse, and the medicine is safe and convenient to use.
Finally, the above embodiments are only for illustrating the technical solutions of the present invention and not for limiting, although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all of them should be covered in the claims of the present invention.
Claims (2)
1. A medicament for treating diabetic ulcers, which is characterized in that: a composition consisting of solute cinnamaldehyde and solvent PEG400, wherein the concentration of cinnamaldehyde in the composition is in the range of 1.2 to 4 μmol/L.
2. The medicament for treating diabetic ulcers according to claim 1, characterized in that: the concentration of cinnamaldehyde in the composition was 4 μmol/L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710335648.8A CN107126413B (en) | 2017-05-12 | 2017-05-12 | Medicine for treating diabetic ulcer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710335648.8A CN107126413B (en) | 2017-05-12 | 2017-05-12 | Medicine for treating diabetic ulcer |
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| Publication Number | Publication Date |
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| CN107126413A CN107126413A (en) | 2017-09-05 |
| CN107126413B true CN107126413B (en) | 2020-11-20 |
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| CN201710335648.8A Active CN107126413B (en) | 2017-05-12 | 2017-05-12 | Medicine for treating diabetic ulcer |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110974781A (en) * | 2020-01-02 | 2020-04-10 | 崔立峰 | Gel for repairing skin wound |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5855414A (en) * | 1981-09-26 | 1983-04-01 | Pola Chem Ind Inc | Preparation for skin |
| CN1662220A (en) * | 2002-06-25 | 2005-08-31 | Wm.雷格利Jr.公司 | Breath freshening and oral cleansing product with cinnamaldehyde |
| CN102718638A (en) * | 2012-05-09 | 2012-10-10 | 湖北远成药业有限公司 | Industrial preparation method of high-yield cinnamaldehyde |
| CN103948575A (en) * | 2014-05-22 | 2014-07-30 | 上海和黄药业有限公司 | Application of cinnamyl aldehyde in preparing medicament for promoting angiogenesis |
-
2017
- 2017-05-12 CN CN201710335648.8A patent/CN107126413B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5855414A (en) * | 1981-09-26 | 1983-04-01 | Pola Chem Ind Inc | Preparation for skin |
| CN1662220A (en) * | 2002-06-25 | 2005-08-31 | Wm.雷格利Jr.公司 | Breath freshening and oral cleansing product with cinnamaldehyde |
| CN102718638A (en) * | 2012-05-09 | 2012-10-10 | 湖北远成药业有限公司 | Industrial preparation method of high-yield cinnamaldehyde |
| CN103948575A (en) * | 2014-05-22 | 2014-07-30 | 上海和黄药业有限公司 | Application of cinnamyl aldehyde in preparing medicament for promoting angiogenesis |
Non-Patent Citations (4)
| Title |
|---|
| Nrf2通路在糖尿病中的研究进展;郑宏庭;《第三军医大学学报》;20140815;第36卷(第15期);第1552-1556页 * |
| Stability of Sulforaphane for Topical Formulation;Stephen J. Franklin, B.S. et al;《Drug Dev Ind Pharm.》;20140430;第40卷(第4期);第494-502页 * |
| 局部应用肉桂醛通过激活 Nrf2 通路促进糖尿病小鼠创口愈合;蔡雷琴，等;《第三军医大学学报》;20170915;第39卷(第19期);第1906-1912页 * |
| 肉桂醛促进高糖条件下皮肤成纤维细胞迁移及机制研究;李文杰，等;《第三军医大学学报》;20170315;第39卷(第5期);摘要、第424页左栏第1段至右栏第1段、第425页第1.3节、第427-428页第3节 * |
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