CN107126413A - A kind of medicine for treating diabetic ulcer - Google Patents

A kind of medicine for treating diabetic ulcer Download PDF

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Publication number
CN107126413A
CN107126413A CN201710335648.8A CN201710335648A CN107126413A CN 107126413 A CN107126413 A CN 107126413A CN 201710335648 A CN201710335648 A CN 201710335648A CN 107126413 A CN107126413 A CN 107126413A
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CN
China
Prior art keywords
medicine
cinnamic acid
diabetic ulcer
gel
wound
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Application number
CN201710335648.8A
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Chinese (zh)
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CN107126413B (en
Inventor
隆敏
郑宏庭
蔡雷琴
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Third Military Medical University TMMU
Second Affiliated Hospital of TMMU
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Second Affiliated Hospital of TMMU
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/11Aldehydes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a kind of medicine for treating diabetic ulcer, by solute:Cinnamic acid and solvent:The concentration range of cinnamic acid is 1.2-20 μm of ol/L in the gel that PEG 400 is constituted, the gel.The medicine of present invention treatment diabetic ulcer, it is gel state, and medicine is applied into wound portion during treatment, can significantly improve diabetes Wound healing, and therapeutic effect is good and safe and convenient to use.

Description

A kind of medicine for treating diabetic ulcer
Technical field
The present invention relates to biomedicine technical field, more particularly to a kind of external used medicine for treating ulcer.
Background technology
Chronic ulcer of skin does not recover for a long time, and ultimately results in amputation, is the main reason that diabetes disable, it would be highly desirable to research solution Certainly.CA is not only a kind of α, β-unsaturation ratified through FDA available for food as the Main Ingredients and Appearance of organic extract in Chinese cassia tree Aldehyde compound (21CFR § 182.60), more by the U.S., " spices manufactures NAB National Association 0f Broadcasters (FEMA) with extract " gives and " typically recognized For safety " operation instruction (NO.2286).In addition substantial amounts of human research describes the systemic pharmacokinetics and peace of its application Full property feature, points out it to have wide potential potential applicability in clinical practice.
At present through clinical research confirmation, skin oxidative stress damage is serious at diabetic ulcer;Recent experimental finds that CA can To promote application on human skin horn cell and migration of fibroblast cells, and intracellular ROS accumulations are reduced, alleviate oxidative stress and damage Wound;Zoopery also further confirms that Nrf2 specific agonist --- cinnamic acid (CA) can be relieved oxidative stress Damage, promotes diabetic ulcer mouse Wound healing.However, the application strategy of Nrf2 activators is not safe and simple at present, its Occupation mode is generally two kinds, such as intraperitoneal injection the corn oil (mouse) containing CA, or in the diet addition 0.1% or 0.5% CA, but above-mentioned best applications mode not for clinical diabetes ulcer treatment, security and convenience are poor.
Accordingly, it would be desirable to find a kind of more preferably application strategy in treatment diabetic ulcer for CA.
The content of the invention
In view of this, diabetic ulcer topical application and safe drugs are treated it is an object of the present invention to provide one kind, to solve Certainly current Nrf2 activators --- the problem of application strategies of the CA in diabetic ulcer be not safe and simple.
The medicine of present invention treatment diabetic ulcer, by solute:Cinnamic acid and solvent:The gel that PEG 400 is constituted, it is described The concentration range of cinnamic acid is 1.2-20 μm of ol/L in gel.
It is preferred that, the concentration of cinnamic acid is 4 μm of ol/L in the gel.
Beneficial effects of the present invention:
The medicine of present invention treatment diabetic ulcer, it is gel state, and medicine is applied into wound portion during treatment, can be shown Writing improves diabetes Wound healing, and therapeutic effect is good and safe and convenient to use.
Brief description of the drawings
Fig. 1 is that Wound healing area changes over time figure;
Fig. 2 is quantitative Wound healing area time history plot;
Fig. 3 is wound organization healing aspect graph.
Embodiment
The invention will be further described with reference to the accompanying drawings and examples.
The present embodiment treats the medicine of diabetic ulcer, by solute:Cinnamic acid and solvent:The gel that PEG 400 is constituted, institute It is 1.2-20 μm of ol/L to state the concentration range of cinnamic acid in gel.
Below exemplified by preparing 4 μm of ol/L of 1mL cinnamic acid gel, the medicine that the present embodiment treats diabetic ulcer is introduced Thing preparation method, it is comprised the following steps that:
Step one:Prepare 1mL 20mmol/L cinnamic acid gel
1) CA molal quantitys contained in 1mL 20mmol/L cinnamic acids gel:
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 are added in 1ml PEG400, then concussion makes CA be dispersed in PEG400 at a high speed, that is, obtains 1mL 20mmol/L cinnamic acid gel.
Step 2:Prepare 100 μm of ol/L cinnamic acid gels of 1mL
1) CA molal quantitys contained in 100 μm of ol/L cinnamic acid gels of 1mL:
N=c × v
nCA=(100 μm of ol/L) × (1mL)=0.1 μm ol
2) volume of the 20mmol/L cinnamic acid gels needed for
C1V1=nCA
V1=nCA/C1
V1=0.1 μm of ol/20mmol/L=5ul
By 5ul steps one) made from 20mmol/L cinnamic acid gel be added in 1ml PEG400, then concussion makes at a high speed CA is dispersed in PEG400, that is, obtains 100 μm of ol/L cinnamic acid gels of 1mL.
Step 3:Prepare 4 μm of ol/L of 1mL cinnamic acid gel
1) CA molal quantitys contained in 4 μm of ol/L cinnamic acid gels of 1mL:
N=c × v
nCA=(4 μm of ol/L) × (1mL)=0.004 μm ol
2) volume of 100 μm of ol/L cinnamic acid gels needed for
C2V2=nCA
V2=nCA/C1
V2=0.004 μm of ol/100 μm of ol/L=40ul
By 40ul step 2) made from 100 μm of ol/L cinnamic acid gel be added in 1ml PEG400, then shake at a high speed CA is dispersed in PEG400, that is, obtain 4 μm of ol/L cinnamic acid gels of 1mL, it is the character of faint yellow hydrogel, one As be stored in 4 DEG C of -20 DEG C of environment, can stablize preserve one week.
The medicine for treating diabetic ulcer below for topical application the present embodiment can remarkably promote diabetes Wound healing Experiment:
8 SKH-1 mouse peritoneal injection 50mg/kg STZ of 8 week old are continued to set up within 5 days the sick mouse model of sugar.Using Random digits table is respectively divided into diabetes group, diabetes+CA groups at random.Implement wound operation within the 4th week after STZ injections, in mouse Diameter 6mm full thickness skin excision wound is set up at back.Polyethylene of the diabetes+CA group partial smearing 20 μ l containing 4 μm of ol/L CA Alcohol 400 (polyethylene glycol 400, PEG 400), diabetes group group is made using the topical applications of PEG 400 of equivalent For control, intervened every 1 day until Wound healing collects skin at edge of wound on the 14th day.Every 1 day monitoring skin wound in postoperative 2 weeks Mouth healing area assesses Healing Rate.
As shown in Figure 1:Real Time Observation diabetes group, the change of the Each point in time of diabetes+CA group Wound healing areas, The Wound healing situation of diabetes+CA group mouse is significantly improved compared with diabetes group.Through each time point wound of quantitative analysis The change (as shown in Figure 2) of mouth healing area, after partial smearing medicine of the present invention, behind the 9th day of Wound healing, wound is cured Speed is closed to dramatically increase (n=8, * P < 0.05).Further compare the difference of each group Wound healing, histological observation the 14th day is each Group wound histomorphological changes, as shown in fig. 3, it was found that the diabetes group surface of a wound still has loose granulation tissue, newborn epithelium is simultaneously The surface of a wound is not completely covered, however, at diabetes group+CA group wounds, newborn epithelium is formed completely, and histology is complete.Above-mentioned knot Fruit shows that the local medicine with present invention treatment diabetic ulcer can significantly improve the healing of diabetic mice wound, and medicine Thing it is safe and convenient to use.
Finally illustrate, the above embodiments are merely illustrative of the technical solutions of the present invention and it is unrestricted, although with reference to compared with The present invention is described in detail good embodiment, it will be understood by those within the art that, can be to skill of the invention Art scheme is modified or equivalent substitution, and without departing from the objective and scope of technical solution of the present invention, it all should cover at this Among the right of invention.

Claims (2)

1. a kind of medicine for treating diabetic ulcer, it is characterised in that:By solute:Cinnamic acid and solvent:It is solidifying that PEG 400 is constituted The concentration range of cinnamic acid is 1.2-20 μm of ol/L in glue, the gel.
2. the medicine for the treatment of diabetic ulcer according to claim 1, it is characterised in that:Cinnamic acid is dense in the gel Spend for 4 μm of ol/L.
CN201710335648.8A 2017-05-12 2017-05-12 Medicine for treating diabetic ulcer Active CN107126413B (en)

Priority Applications (1)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110974781A (en) * 2020-01-02 2020-04-10 崔立峰 Gel for repairing skin wound

Citations (4)

* Cited by examiner, † Cited by third party
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

Patent Citations (4)

* Cited by examiner, † Cited by third party
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 (7)

* Cited by examiner, † Cited by third party
Title
STEPHEN J. FRANKLIN, B.S. ET AL: "Stability of Sulforaphane for Topical Formulation", 《DRUG DEV IND PHARM.》 *
何天白,等: "《海外高分子科学的新进展》", 30 September 1997 *
姚静,等: "《药用辅料应用指南》", 31 August 2011 *
方亮,等: "《药剂学 第3版》", 31 March 2016 *
李文杰,等: "肉桂醛促进高糖条件下皮肤成纤维细胞迁移及机制研究", 《第三军医大学学报》 *
蔡雷琴,等: "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", 《第三军医大学学报》 *
郑宏庭: "Nrf2通路在糖尿病中的研究进展", 《第三军医大学学报》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110974781A (en) * 2020-01-02 2020-04-10 崔立峰 Gel for repairing skin wound

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