CN109381466A - Promote the therapeutic agent of diabetic wound healing - Google Patents
Promote the therapeutic agent of diabetic wound healing Download PDFInfo
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- CN109381466A CN109381466A CN201710668802.3A CN201710668802A CN109381466A CN 109381466 A CN109381466 A CN 109381466A CN 201710668802 A CN201710668802 A CN 201710668802A CN 109381466 A CN109381466 A CN 109381466A
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- rebamipide
- pharmaceutical composition
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- diabetic
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- 230000029663 wound healing Effects 0.000 title claims abstract description 22
- 239000003814 drug Substances 0.000 title claims abstract description 18
- 229940124597 therapeutic agent Drugs 0.000 title description 3
- ALLWOAVDORUJLA-UHFFFAOYSA-N Rebamipida Chemical compound C=1C(=O)NC2=CC=CC=C2C=1CC(C(=O)O)NC(=O)C1=CC=C(Cl)C=C1 ALLWOAVDORUJLA-UHFFFAOYSA-N 0.000 claims abstract description 40
- 229950004535 rebamipide Drugs 0.000 claims abstract description 40
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
- 229940079593 drug Drugs 0.000 claims abstract description 14
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4704—2-Quinolinones, e.g. carbostyril
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/26—Organic compounds containing nitrogen
- C11D3/32—Amides; Substituted amides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to medicines, more particularly to a kind of medical usage of Rebamipide.Animal experiments prove that Rebamipide can be effectively facilitated the wound healing of diabetes.The present invention also provides a kind of pharmaceutical compositions for promoting diabetic wound healing.
Description
Technical field
The present invention relates to for promoting the pharmaceutical composition containing Rebamipide of diabetic wound healing.
Background technique
Diabetes are the metabolic diseases for seriously threatening human health, it has also become after angiocarpy, tumour, AIDS
The disease of the fourth-largest easy causing death.Statistical data shows that there are 2.85 hundred million diabetics in the current whole world, it is predicted that the year two thousand thirty
Global diabetic is up to 4.39 hundred million, and the complication that diabetes are caused then becomes patient and disables and lethal master
Want reason.In many complication of diabetes, diabetic's wound-healing abilities are impaired be diabetes one it is typical simultaneously
Disease is sent out, if chronic damage and disease of bursting occurs in foot, it is likely that cause diabetes, serious person even results in amputation,
This has become the highest disease of diabetic's admission rate, so far still without effective treatment method.
Diabetic into the cell, extracellularly is likely to be dehydrated, influences wound healing when blood glucose is excessively high.Together
When, blood sugar in diabetic patients control imbalance, body supports antibacterial ability and can reduce.Hyperglycemia causes cell to transport oxygen to tissue
Ability reduce, poor blood circulation influences wound healing.On the other hand, blood glucose rise easily causes microangiopathies, damages blood
Pipe and nerve cause routed disease to be difficult to heal.
Therefore, it is badly in need of seeking a kind of therapeutic agent that can promote diabetic wound healing.
Rebamipide (Rebamipide) is the drug of the treatment gastric ulcer listed by Japanese great Zhong company in nineteen ninety.It grinds
Study carefully discovery, Rebamipide has the effects that promote stomach lining ulcer healing, eliminates oxygen radical, is anti-oxidant.Point of Rebamipide
Minor are as follows: C19H15ClN2O4Molecular weight are as follows: 370.07, structural formula is as follows:
Summary of the invention
The purpose of the present invention is intended to provide a kind of new medical usage of Rebamipide.Surprisingly, it was found that auspicious
Ba Paite is obviously promoted the formation of diabetic lesions model promoting epidermization and granulation tissue.Accordingly, the present invention provides a kind of auspicious
Application of the Ba Paite in the pharmaceutical composition that preparation promotes the formation of diabetic wound promoting epidermization and granulation tissue.
The present invention provides a kind of Rebamipides to prepare the pharmaceutical composition for shortening diabetic wound healing time
In application.
The present invention provides a kind of Rebamipides in the pharmaceutical composition that preparation promotes diabetic wound healing
Using.
The present invention provides a kind of application of Rebamipide in the pharmaceutical composition of preparation treatment diabetes.
The present invention provides the pharmaceutical compositions that a kind of Rebamipide is difficult to heal in preparation prevention diabetic wound
In application.
The present invention provides a kind of Rebamipides to be difficult to the drug to heal or food in preparation prevention diabetic wound
Or the application in cosmetics or articles for washing.
The present invention provides a kind of application of Rebamipide in the drug or food of preparation prevention diabetes.
The present invention provides a kind of Rebamipide answering in the pharmaceutical composition that preparation treats or prevents diabetic gangrene
With.
The present invention provides a kind of Rebamipides in the drug or food or cosmetics of preparation prevention diabetic gangrene or to wash
Wash the application in articles.
Rebamipide of the invention can be used alone or be used in the form of pharmaceutical composition.The present invention provides a kind of rush
Into the pharmaceutical composition of diabetic wound healing, which is characterized in that contain therapeutically effective amount in described pharmaceutical composition
Rebamipide is as active constituent and pharmaceutically acceptable carrier.Preferably, pharmaceutical composition of the invention contains 0.1-
The Rebamipide as active constituent of 99.9% weight percent." pharmaceutically acceptable carrier " will not be destroyed of the invention
The pharmaceutical active of Rebamipide, while its effective dose, dosage when can play pharmaceutical carrier effect are nontoxic to the human body.
The pharmaceutical composition provided by the invention for promoting diabetic wound healing can be used for preventing and treating diabetes
The various epidermis injuries of patient, including diabetes, diabetes canker sore and various diabetic dermopathies.
The pharmaceutically acceptable carrier includes but is not limited to: soft phosphatide, aluminum stearate, aluminium oxide, ion exchange material
Material, self-emulsifying drug delivery system, tween or other surfaces activator, haemocyanin, buffer substance such as phosphate, amino second
Acid, sorbic acid, water, salt, electrolyte for example sulfate protamine, disodium hydrogen phosphate, potassium hydrogen phosphate, common salt, zinc salt, magnesium silicate,
Saturated fatty acid partial glyceride mixtures etc..
Other common excipient substance such as adhesives (such as microcrystalline cellulose), filler (such as starch, glucose, anhydrous lactitol
Sugar and lactose bead), (such as cross-linked pvp, croscarmellose sodium, low has replaced third at crosslinked carboxymethyl fecula sodium to disintegrating agent
Base cellulose), lubricant (such as magnesium stearate) and sorbefacient, absorption carrier, flavouring agent, sweetener, excipient, dilution
Agent, wetting agent etc..
Rebamipide of the invention and its pharmaceutical composition can be prepared by conventional method in that art and can pass through enteron aisle
Or non-bowel or topical routes.Oral preparation include capsule, tablet, oral solution, granule, pill, powder, sublimed preparation,
Paste etc.；Non-intestinal drug delivery agent includes injection etc.；Local administration preparation includes creme, patch, ointment, gelling agent and spray
Mist agent etc..Preferably local administration preparation.
The administration route of Rebamipide of the invention and its pharmaceutical composition can for it is oral, sublingual, percutaneous, through muscle
Or subcutaneous, mucocutaneous, vein etc..
Other than drug is made, it is each that antioxidant, pigment, enzyme preparation etc. can also be added in Rebamipide of the invention
Kind food additives, are made health food by the conventional method of this field.
Detailed description of the invention
Fig. 1 embodies influence of the Rebamipide to db/db mouse wound healing, and as seen from Figure 1, postoperative 6th day starts extremely
16th day, the wound area of Rebamipide administration group db/db mouse was significantly less than blank control group, and the two has significant difference (P
< 0.05).
Fig. 2 healing days 14.8 days, substantially less than blank pair as it can be seen that Rebamipide administration group db/db mouse wound is averaged
According to group (21.2 days) (P < 0.001).
Specific embodiment
The contents of the present invention are illustrated below by embodiment.In the present invention, embodiments discussed below be in order to
It preferably illustrates the present invention, is not for limiting the scope of the invention.
Rebamipide can be obtained by commercial sources from Sigma chemical company etc. purchase, or with the routine of this field
Method synthesis.Its purity meets medicinal standard.
In the following examples, the experimental methods for specific conditions are not specified, usually according to normal condition or according to institute, manufacturer
It is recommended that condition.Unless otherwise stated, otherwise all percentage, ratio, ratio or number be by weight.
Unless otherwise defined, it anticipates known to all professional and scientific terms as used herein and one skilled in the art
Justice is identical.In addition, any method similar to or equal to what is recorded and material can be applied to the method for the present invention.Wen Zhong
The preferred implement methods and materials are for illustrative purposes only.
The feature that the features described above or embodiment that the present invention mentions are mentioned can be in any combination.Patent specification is taken off
All features shown can be used in combination with any composition form, and each feature disclosed in specification any can provide phase
The alternative characteristics of same, impartial or similar purpose replace.Therefore except there is special instruction, revealed feature is only impartial or similar
The general example of feature.
Embodiment 1
Rebamipide acts on the promotion wound healing of diabetic lesions model
1, experimental material
1.1 drug
Rebamipide (molecular weight: 370.07, HPLC purity >=99%, sigma companies)
1.2 experimental animal
The db/db female mice (12 weeks) of 50 ± 5g of weight is provided by dimension tonneau China's Experimental Animal Center, is placed in routine
Feeding environment, sub-cage rearing, ad lib and drinking-water.
2, experimental method
2.1 diabetic lesions model foundations
It is shaved after isoflurane anesthesia using the modeling method (Nature Protocols 2013,8:302-309) in adopted offer
Go skin of back, depilatory cream depilation, conventional transdermal disinfection, using the punch of diameter 6mm respectively in two lateral incision one of back backbone
Circular incision, as deep as fascia.To prevent wound from shrinking automatically, respectively its edge be stained with silicone gasket (0.5mm thick, it is interior
Diameter 9mm, outer diameter 18mm), and and skin closure.The operation same day is calculated as postoperative 0th day, and so on.
2.2 groupings and medication
Blank control group: sterile ultrapure water (15uL/wound)
Positive controls: vascular epidermal growth factor (VEGF) (1.0mg/mL, 15 μ L/wound).
Medication group: Rebamipide (15mg/mL, 15uL/wound).
Every group 10, the operation same day starts, and is administered once within every two days, covers wound using biological permeability film after administration.
2.3 wound healings observation:
The operation same day starts, and every other day, acquires wound photo in fixed height using digital camera, passes through Image J
Software calculates wound area.
2.4 statistical analysis
All experimental datas are repeated 3 times, and are as a result indicated with mean+SD, using 13.0 statistical software of SPSS
Experimental data is examined using One-way ANOVA (One-way ANOVA) and LSD, P < 0.05 has aobvious for statistically difference
Work property.
3, result
Influence of 3.1 Rebamipides to db/db mouse wound healing.
Influence of 1. Rebamipide of table to db/db mouse wound area
To sum up result of study shows that Rebamipide can be effectively facilitated the wound healing of diabetic mice, significant to shorten
The time of wound healing.
Embodiment 2
The preparation of Pharmaceutical composition: tablet
Rebamipide (1g) is mixed with 23g lactose and 5.7g microcrystalline cellulose with mixing machine.With roller bearing compacting machine by institute
Mixture compression moulding is obtained, flake sheeted product is worth.The laminar sheeted product is pulverized with beater grinder,
Gained granular material is set to pass through 20 mesh sieves.A 0.3g light silicon dioxide and 0.3g magnesium stearate are added to and have been sieved
Material in, and mix.The pelleter tabletting of gained mix products.
Embodiment 3
The preparation of Pharmaceutical composition: spray
Taking mass ratio is that 1: 0.5 Rebamipide and Chitosan powder are dissolved in 75% ethanol solution, is stirred using magnetic force
It mixes and is stirred and evenly mixed on machine, prepare drug solution.Mass ratio is taken to be dissolved in for 1: 1.26 polyvinylpyrrolidone and glycerol powder
In 75% ethanol solution, using stirring and evenly mixing on magnetic stirrer, pore solution is prepared.Take polyvinyl butyral powder end molten
Solution, using stirring and evenly mixing on magnetic stirrer, prepares film forming solution in 75% ethanol solution.Calamine powder is taken to be dissolved in
In 75% ethanol solution, using stirring and evenly mixing on magnetic stirrer, preparation restrains solution.Said medicine solution, pore is molten
Liquid, film forming solution and convergence solution import reaction kettle, stir, obtain A liquid.Water-soluble coenzyme is added into A liquid
Dissolution is sufficiently stirred in Q10, obtains B liquid.Na-alginate is added into B liquid, dissolution is sufficiently stirred, forms stablizing solution to get spray
Agent.
In above-described embodiment, polyvinyl butyral derives from Tianjin Hua Lvyuan Chemical trade Co., Ltd, polyethylene pyrrole
Pyrrolidone beautifies work from Guangzhou Guangdong, and Na-alginate derives from the global seaweed auxiliary agent in Lianyun Harbour Co., Ltd, content 20%
Water-soluble coenzyme Q10 is from the big magnificent great achievement medication chemistry Co., Ltd in Wuhan.
Various aspects of the present invention have been described above.However, it should be understood that without departing from spirit of that invention
Under the premise of, those skilled in the art can carry out equivalent change and modification to it, and the change and modification equally fall into present application
The coverage area of appended claims.
Claims (12)
1. Rebamipide is in the pharmaceutical composition that preparation promotes diabetic wound promoting epidermization and granulation tissue to be formed
Using.
2. application of the Rebamipide in the pharmaceutical composition that diabetic wound healing time is shortened in preparation.
3. application of the Rebamipide in the pharmaceutical composition that preparation promotes diabetic wound healing.
4. Rebamipide is difficult to the application in the pharmaceutical composition to heal in preparation prevention or treatment diabetic wound.
5. Rebamipide is difficult to the drug to heal or food or cosmetics in preparation prevention or treatment diabetic wound or washes
Wash the application in articles.
6. application of the Rebamipide in the pharmaceutical composition of preparation treatment diabetes.
7. application of the Rebamipide in the drug or food or cosmetics or articles for washing of preparation prevention diabetes.
8. application of the Rebamipide in the pharmaceutical composition that preparation treats or prevents diabetic gangrene.
9. application of the Rebamipide in the drug or food or cosmetics or articles for washing of preparation prevention diabetic gangrene.
10. a kind of pharmaceutical composition for promoting diabetic wound healing, which is characterized in that contain in described pharmaceutical composition
The Rebamipide of therapeutically effective amount is as active constituent and pharmaceutically acceptable carrier.
11. such as the pharmaceutical composition of claim 10, which is characterized in that the diabetic wound comes from diabetes, sugar
Urinate sick canker sore and various diabetic dermopathies.
12. such as the pharmaceutical composition of claim 10, which is characterized in that described pharmaceutical composition is capsule, tablet, takes orally
Liquid, granule, pill, powder, sublimed preparation, paste, injection, creme, patch, ointment, gelling agent and spray.
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| CN201710668802.3A CN109381466A (en) | 2017-08-02 | 2017-08-02 | Promote the therapeutic agent of diabetic wound healing |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710668802.3A CN109381466A (en) | 2017-08-02 | 2017-08-02 | Promote the therapeutic agent of diabetic wound healing |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112494488A (en) * | 2020-06-17 | 2021-03-16 | 中国药科大学 | Application of rebamipide in preventing alopecia and growing hair |
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| CN102481298A (en) * | 2009-08-25 | 2012-05-30 | 天主教大学校产学协力团 | Pharmaceutical composition for preventing or treating rheumatoid arthritis, containing rebamipide |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102481298A (en) * | 2009-08-25 | 2012-05-30 | 天主教大学校产学协力团 | Pharmaceutical composition for preventing or treating rheumatoid arthritis, containing rebamipide |
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| HUNJOO HA等: "Effects of Rebamipide in a Model of Experimental Diabetes and on the Synthesis of Transforming Growth Factor-βand Fibronectin, and Lipid Peroxidation Induced by High Glucose in Cultured Mesangial Cells", 《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112494488A (en) * | 2020-06-17 | 2021-03-16 | 中国药科大学 | Application of rebamipide in preventing alopecia and growing hair |
| CN112494488B (en) * | 2020-06-17 | 2022-01-18 | 中国药科大学 | Application of rebamipide in preventing alopecia and growing hair |
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