CN106822075A - Application of the melbine in wound healing is promoted - Google Patents
Application of the melbine in wound healing is promoted Download PDFInfo
- Publication number
- CN106822075A CN106822075A CN201710205051.1A CN201710205051A CN106822075A CN 106822075 A CN106822075 A CN 106822075A CN 201710205051 A CN201710205051 A CN 201710205051A CN 106822075 A CN106822075 A CN 106822075A
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- Prior art keywords
- melbine
- wound healing
- wound
- application
- healing
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Classifications
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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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Abstract
The present invention relates to biomedicine technical field, and in particular to application of the melbine in wound healing is promoted.Promoting healing effect pharmacological experiment through db/db diabetic mice wounds shows that melbine can substantially speed up the speed of wound healing, shows that it has the effect for promoting wound healing, therefore can be used to prepare the medicine of treat wound healing.
Description
Technical field
The present invention relates to biomedicine technical field, and in particular to melbine and combinations thereof heals for treat wound
Purposes, it is chronic refractory in particular for patient body-surfaces such as diabetes, wound, varication, vascular sclerosis, paraplegia long-term beds
Close the surface of a wound.
Background technology
Wound be normal skin (tissue) the external worlds such as surgical operation, external force, heat, electric current, chemical substance, low temperature cause injury because
The lower caused infringement of the body internal factor effect such as son and local blood supply obstacle, is often accompanied by the destruction of skin integrity
And the loss of a certain amount of normal structure, while the normal function of skin is damaged.Body surface chronic wounds (are commonly called as ulcer),
Also chronic wounds or chronic wound are, refer to that the treatment caused by a variety of causes is not healed without substantially healing for more than 1 month yet yet
The surface of a wound of tendency.International wound healing association is for the definition of chronic wound：Cannot be by normally in order and timely repairing
Process reaches the surface of a wound dissected with functionally good working condition.Clinically refer to that the surface of a wound that a variety of causes is formed was controlled through more than 1 month more
Treatment fails healing, also without healing tendency person.Betide the long-term surface of a wound not healed of body surface, mainly including traumatic ulcer, under
Limb venous ulcer, pressure ulcer and diabetic ulcer etc..Chronic wound has that pathogenesis is complicated, the course of disease is long, treatment
Difficulty is big and be the emphasis and difficult point of wound repair research the features such as medical expense high.
From the sixties in 20th century, numerous scholars prove wound dressing by substantial amounts of surface of a wound experimental study and clinical practice
Function with wound healing.Wound dressing is divided into traditional dressing, biological dressing, artificial synthesized according to the difference of its material
Dressing and growth factor dressing etc..Promoting the method for body surface chronic wounds healing in recent years also includes genetically engineered drug
(growth factor) class, traditional medicine class, biological control class (such as maggot) and stem cell and organizational project.Growth factor genoid
Engineering medicine is a kind of effective biological agent for being applied to acute and chronic Wound treating in recent years, including recombination human platelet growth
The factor (PDGF), recombined human and bFGF bovine basic fibroblast growth factor (bFGF) and recombinant human epidermal cell growth factor
Sub (EGF) etc..
Melbine is applied to alone diet and exercise therapy can not obtain the diabetes B patient of good control.This product can
Independent medication, can also share with sulfonylurea or insulin.The hypoglycemic mechanism of melbine is：1 increases surrounding tissue to pancreas
The sensitiveness of island element, increases the glucose utilization of insulin-mediated.2 increase profit of the noninsulin dependent tissue to glucose
With such as brain, haemocyte, kidney medulla, enteron aisle, skin.3 suppress gluconeogenesis function of liver, reduce glycogen output.4 suppress intestinal wall
Cellular uptake glucose.Different from insulin action, melbine drops blood to normal person without Fatty synthesis effect is promoted without obvious
Sugar effect, hypoglycemia is not caused typically when being used alone to diabetes B.In the prior art, wound is promoted on melbine
The effect of healing, yet there are no report.
The content of the invention
First purpose of the invention is directed to deficiency of the prior art, there is provided melbine promotes wound to heal in preparation
Application in the product of conjunction.
Second object of the present invention is directed to deficiency of the prior art, there is provided melbine is slow in preparation treatment body surface
Property it is refractory close the surface of a wound product in application.
To realize above-mentioned first purpose, the present invention is adopted the technical scheme that：
Application of the melbine in the product for promoting wound healing is prepared.
Further, the wound healing refer to burn, scald, the surface of a wound of the wound healing of ultraviolet injury or wound is healed
Close.
Further, the melbine is used as sole active agent.
Further, described product includes one or more in medicine, reagent, food, health products.
Further, the melbine can be used alone or be used in the form of pharmaceutical composition, the medicine group
Melbine of the compound comprising therapeutically effective amount, its pharmaceutically acceptable salt or its prodrug, and carrier pharmaceutically.
To realize above-mentioned second purpose, the present invention is adopted the technical scheme that：
Application of the melbine in the product for preparing treatment body surface chronic wounds.
Further, the body surface chronic wounds refer to the diabetic ulcer that is caused by diabetes, ischemic, pressure or
Pressure ulcer.
Further, the melbine is used as sole active agent.
Further, described product includes one or more in medicine, reagent, food, health products.
Further, the melbine can be used alone or be used in the form of pharmaceutical composition, the medicine group
Melbine of the compound comprising therapeutically effective amount, its pharmaceutically acceptable salt or its prodrug, and carrier pharmaceutically.
Further, one or more in the carrier pharmaceutically, including excipient, such as starch or water；Lubricant, such as
One or more in glycerine or magnesium stearate etc.；Disintegrant, such as microcrystalline cellulose；In filler, such as starch or lactose
One or more；Bonding agent, such as pregelatinized starch, dextrin, cellulose derivative, alginates, gelatin or polyvinylpyrrolidine
One or more in ketone etc.；One or more in osmotic pressure regulator, such as glucose, sucrose, sorbierite or mannitol；
Diluent, such as water；One or more in disintegrant, such as agar, calcium carbonate or sodium acid carbonate；Sorbefacient, such as season
Ammonium compounds etc.；Surfactant, such as hexadecanol；One or more in absorption carrier, such as kaolin or soap clay；
One or more in lubricant, such as talcum powder, calcium stearate, magnesium stearate or polyethylene glycol；Furthermore it is also possible in medicine
Other assistant agents, such as one or more in flavouring agent or sweetener are added in composition.
Further, the melbine can be applied in the form of a kind of its pharmaceutically acceptable salt, specific its pharmacy
Upper acceptable salt includes：Hydrochloride, acetate, benzoate, citrate, fumarate, embonate, chlorobenzene oxygen
Guanidine-acetic acid salt, oxyacetate, aspartate, mesylate, maleate, p-chlorophenyl isobutyrate, formates, lactic acid
Salt, succinate, sulfate, tartrate, cyclohexane-carboxylic acid salt, trimethoxybenzoic acid salt, tosilate, adamantane
Carboxylate, glycoxylate, glutamate, Bi Ka Wan keto carboxylic acids salt, naphthalene sulfonate, 1- glucose phosphates, nitrate, sulfurous acid
Salt, dithionate or；Phosphate.Wherein preferred salt form is hydrochloride, fumarate, embonate or chlorobenzene oxygen
Guanidine-acetic acid salt.
The invention has the advantages that：
The present invention carries out experimental study by multiple compounds, screens and confirm the new activity and new use of melbine
On the way.Melbine can significantly add to be shown to the promoting healing effect pharmacological experiment of db/db diabetic mice wounds through melbine
The speed of fast wound healing, shows that it has the effect for promoting wound healing, therefore can be used for the medicine of treat wound healing.This
Invention provide not only the new therapeutical uses of melbine, also for the treatment of chronic wound provides new medicine.
Brief description of the drawings
Accompanying drawing 1 is that Or Metformin In Treating accelerates db/db diabetic mice wound healings.Normal group is followed successively by figure from top to bottom
(Con), db/db diabetes models+melbine group (db/db+Met), db/db diabetic model groups (db/db)；*P<
0.05vs.Control；#P<0.05vs.db/db；N=5.
Specific embodiment
The invention will be further elucidated with reference to specific embodiments.It should be understood that these embodiments are merely to illustrate this hair
Bright rather than limitation the scope of the present invention.In addition, it is to be understood that after the content for having read record of the present invention, art technology
Personnel can make various changes or modifications to the present invention, and these equivalent form of values equally fall within the application appended claims and limited
Fixed scope.
Term used herein " acceptable ", refers to the health of a prescription component or active component to general treatment target
There is no undue adverse effect.
Term used herein " treatment ", including relax, suppress or improve disease symptom or situation；Suppress complication
Produce；Improve or prevent potential metabolic syndrome；Suppress the generation of disease or symptom, such as development of control disease or situation；Subtract
Light disease or symptom；Disease or symptom is set to go down；The complication that mitigation is caused by disease or symptom, or prevention or treatment are by disease
Or the sign that symptom causes.As used herein, a certain compound or pharmaceutical composition, after administration, can make a certain disease, symptom
Or situation is improved, espespecially its severity is improved, delayed onset, slows down disease progression, or reduce the state of an illness duration.
No matter fix administration or interim administration, be administered continuously or interrupted continuous administration, can be attributed to or the situation relevant with administration.
Term used herein " pharmaceutically acceptable " herein refers to a kind of material, such as carrier or dilution, will not make chemical combination
The bioactivity or property of thing disappear, and relative nontoxic, e.g., give individual something, will not cause undesired biotic influence
Or in harmful manner with any component that it contains interact.The example of pharmaceutically acceptable carrier includes one or more
Water, salt solution, PBS, glucose, glycerine or ethanol etc. and combinations thereof in one or more.In many situations
Under, isotonic agent is preferably included in the composition, for example, sugar, such as mannitol, sorbierite, the polyalcohol of sorbierite or chlorination
One or more in sodium etc..Pharmaceutically acceptable carrier can also include a small amount of auxiliary substance, such as wetting agent or breast
One or more in agent, preservative or buffer solution etc..
At specifically used aspect, melbine of the present invention can be used alone, can also be with other many chemical substances
It is applied in combination.No matter whether these chemical substances have bioactivity or the function with treatment disease, including miscellaneous function is such as
Collaboration amplification, antagonism alleviate side effect of melbine etc., and these chemical substances are including pharmaceutically acceptable
One or more in carrier, food, natural products, chemical synthetic drug or human administration etc.；Preferably include pharmaceutically may be used
One or more in carrier or food of receiving etc.；Further preferably pharmaceutically acceptable carrier.
Melbine used is white powder, content in following examples>99%, rank is medical grade.
The melbine of embodiment 1 is acted on the promoting healing of db/db diabetic mice wounds
(1) material
1. animal
Adult C57BL/KSJ db/db (db/db) mouse, male, body weight 45g or so, test purchased from The 2nd Army Medical College
Animal center.Adult C57BL/6J mouse, male is compareed as normal group.During experiment, animal is kept for the week of each 12h of day night
Phase circulation, free diet and drinking-water, Animal House temperature setting is in 22 DEG C or so, relative humidity 70% or so.Experimental animal makes
With the agreement for obtaining the care of animal mechanism of The 2nd Army Medical College, meet the management guideline of correlation, experimentation animal all obtains people
Property is treated.
2. reagent
3. instrument and equipment
4. main solution is prepared
(1) 1% sodium carboxymethylcellulose (CMCNa)：Sodium carboxymethylcellulose 0.6g, distilled water 60ml, uses magnetic agitation
Device is stirred and evenly mixed overnight, is waited and fully mix jelly, and the used time dilutes 1 times into working solution, puts room temperature preservation.
(2) melbine：Melbine 125mg, 1% sodium carboxymethylcellulose 1ml, distilled water 1ml, are fully ground with mortar
Mill, is made into the melbine of 62.5mg/ml, and mouse stomach 14d is given by every amount of 250mg/kg/d, now with the current.
(3) 4% chloraldurates：2g chloraldurates are weighed, is dissolved in 50ml distilled waters, as 4% chloraldurate.
(2) method
The foundation of db/db diabetic mice wound models
Experiment point 3 groups, i.e. normal group, db/db diabetic model groups, db/db diabetes models+melbine group.When dynamic
After thing blood sugar concentration rises to 250mg/dL mono- week, treatment group gives melbine 250mg/kg/d × 14d, normal group and db/db
Diabetic mouse model group gives the CMCNa solution of Isodose.Chloraldurate 350mg/kg anesthetized mices are used afterwards, use electricity
Dynamic shaver and depilatory cream slough mouse back hair, and the diameter about circle of 6mm is cut in mouse back with the card punch of diameter 6mm
Shape region, sets up wound, daily to numbered mouse Taking Pictures recording wound healing situation, using Image-Pro-Plus softwares
Calculate wound area.
(3) experimental result
Can we attempt clear and definite melbine improve the wound-healing abilities of diabetes B mouse, and we are using 2 types sugar
Urine disease db/db mouse models, melbine continuous gavage under mouse anesthesia state, a radius is cut at its back after 2 weeks
The circular wound of 6mm, continuous 14 days every situations for observing its wound healing for 2 days.
As shown in Figure 1：At the 14th day, compared with normal group, the speed of wound healing of diabetes B model group mouse was obvious
Reduce (100.0 ± 0.0%vs.db/db of normal group mouse 62.0 ± 1.4%, p<0.05).Or Metformin In Treating group and diabetes mould
Type group is compared, and its wound-healing abilities is remarkably reinforced, and wound healing area has approached healing, about 84.0 ± 1.3% within the 14th day.Card
Bright melbine can promote the wound healing of diabetes B mouse.
(4) experiment conclusion
Melbine has the effect for promoting wound healing.
The preparation of the dimethyldiguanide tablet of embodiment 2
Preparation technology：HPMC is dissolved in suitable quantity of water, 8% solution is made, lactose is dissolved in hydroxypropyl
Cellulose solution is used as binder solution.Melbine ground 100 mesh sieves, is mixed together with microcrystalline cellulose and uses adhesive matter
Grain.Obtained particle adds magnesium stearate to be well mixed, and compressing tablet is carried out with tablet press machine, obtains diformin tablet.
The preparation of the melbine capsule of embodiment 3
Preparation technology：(1) by melbine, microcrystalline cellulose, 2% Hydroxypropyl methylcellulose premix and wet granulation；(2) it is right
The particle that wet granulation is obtained is dried and whole grain, obtains dry particle；(3) dry particle is always mixed with magnesium stearate,
Always mixed particle；(3) capsule charge is carried out to total mixed particle, obtains melbine capsule preparations.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
Member, on the premise of the inventive method is not departed from, can also make some improvement and supplement, and these are improved and supplement also should be regarded as
Protection scope of the present invention.
Claims (7)
1. application of the melbine in the product for promoting wound healing is prepared.
2. application according to claim 1, it is characterised in that the wound healing refers to burn, scald, ultraviolet injury
Wound healing or wound wound healing.
3. application of the melbine in the product for preparing treatment body surface chronic wounds.
4. application according to claim 3, it is characterised in that the body surface chronic wounds refer to by diabetes,
Diabetic ulcer or pressure ulcer that ischemic, pressure cause.
5. according to any described applications of claim 1-4, it is characterised in that the melbine is used as sole active agent.
6. according to any described applications of claim 1-4, it is characterised in that described product include medicine, reagent, food,
One or more in health products.
7. according to any described applications of claim 1-4, it is characterised in that the melbine can be used alone or with
The form of pharmaceutical composition is used, melbine of the described pharmaceutical composition comprising therapeutically effective amount, and its is pharmaceutically acceptable
Salt or its prodrug, and carrier pharmaceutically.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110179776A (en) * | 2019-05-31 | 2019-08-30 | 宁夏医科大学 | The new application and combination with metformin object of melbine and the preparation method and application of composition |
| CN112494469A (en) * | 2020-07-30 | 2021-03-16 | 吴学雷 | Application of metformin in preparation of medicament for preventing and/or treating scar |
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| CN1635880A (en) * | 2000-05-26 | 2005-07-06 | 国家科研中心 | Use of biguanide derivatives for making a medicine having a wound healing effect |
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| CN1635880A (en) * | 2000-05-26 | 2005-07-06 | 国家科研中心 | Use of biguanide derivatives for making a medicine having a wound healing effect |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110179776A (en) * | 2019-05-31 | 2019-08-30 | 宁夏医科大学 | The new application and combination with metformin object of melbine and the preparation method and application of composition |
| CN110179776B (en) * | 2019-05-31 | 2022-09-06 | 宁夏医科大学 | New application of metformin, metformin composition and preparation method and application of metformin composition |
| CN112494469A (en) * | 2020-07-30 | 2021-03-16 | 吴学雷 | Application of metformin in preparation of medicament for preventing and/or treating scar |
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