CN104940934B - A kind of pharmaceutical composition and its application for being used to promote skin healing - Google Patents
A kind of pharmaceutical composition and its application for being used to promote skin healing Download PDFInfo
- Publication number
- CN104940934B CN104940934B CN201510379777.8A CN201510379777A CN104940934B CN 104940934 B CN104940934 B CN 104940934B CN 201510379777 A CN201510379777 A CN 201510379777A CN 104940934 B CN104940934 B CN 104940934B
- Authority
- CN
- China
- Prior art keywords
- skin
- wound
- healing
- pharmaceutical composition
- anticholinesterase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of pharmaceutical composition for being used to promote skin healing, it includes muscarinic acceptor blocker and anticholinesterase.Said composition is applied to the individual (including humans and animals) with skin wound, so that new granulation tissue is thicker, collagen content is higher, epidermis healing rate is very fast, and without obvious toxic-side effects, had no significant effect for rat diet, body weight and hepatic and renal function.By pharmaceutical composition preparation of the invention for promoting the medicine of skin healing preferably epidermis can be promoted to heal, and without obvious toxic-side effects, there is preferable application prospect.
Description
Technical field
The invention belongs to skin healing pharmaceutical technology field, be related to a kind of pharmaceutical composition for being used to promote skin healing and
It is applied.
Background technology
Skin is body defenses environmental stimuli and first of barrier of damage.Mechanicalness is caused injury skin caused by the factor and each
The damage of tissue will cause the situations such as microorganism invasion, moisture and protein-loss, endocrine and immune dysfunction, severe patient
Body can be caused dead.In many treatment of diseases, such as required surgical operation will also result in serious skin and internal organs wound
Wound.From the point of view of conventional clinical practice experience, in wound or the agglutination of the surgical patient surface of a wound, otch and various previous anastomotics
In, such as generation healing is bad causes the surface of a wound or infection of incisional wound, disruption of wound, and intestines occur as the healing of alimentary tract anastomosis mouth is bad
Complication, the lighters such as leakage, pancreas leakage or courage leakage can reduce the actual effect of operative treatment, and severe one then can directly threaten the life of patient
Safety.Therefore, the treatment of various Wound healings is promoted to play vital effect for the life and health of the mankind.
It is more at present using the improvement wound healing of external application auxiliary material for the small area wound of skin surface.It is medical according to material
Dressing can be divided into natural class dressing, synthesis class dressing and combine dressing.The traditional plant dressing such as gauze, bandage is so far
Most widely used a kind of natural class dressing, can absorb wound exudate, prevent the generation of local hydrops, but shortcoming is easy
Dry and easy adhesion wound.Synthesis class external application dressing is a kind of more dressing of current research, and its species is various, mainly profit
With high molecular special nature, such as film forming, antibiotic property, the wet environment of appropriate cell growth is provided for the surface of a wound；It is such as bright
The bearing hydrocolloid dressing that glue, pectin and carboxymethyl cellulose are mixed, there is good mechanical property, but after a large amount of exudates of absorption
The surface of a wound may be polluted；Water-soluble high-molecular material or monomer are processed into the hydrogel to be formed through special process to apply
Material, good biocompatibility, absorbability is strong, can reach the resistance aseptic effect of bacterium, but easily dry and become with wound close adhesion
Firmly, sense of discomfort is caused.Combine dressing is generally multilayer dressing, and outer layer is high polymer material, and internal layer is the group that biomaterial is formed
Mould assembly dressing, the characteristics of high polymer material resistance bacterium is ventilative and the good histocompatbility of biomaterial are combined, had good
Water penetration and gas permeability, but without anastalsis；These methods easily cause wound dehydrates, are unfavorable for epithelial cell and creep, dressing
Easily with the viscous connection of wound, mechanical damage, unfavorable wound healing are easily caused during dressing；Moreover, it is particularly for big surgical operation
Internal organs, deep tissue and skin trauma caused by thoracic and abdominal operation are without any effect, therefore the wound healing of deep tissue
The effect of wound healing may be needed to can be only achieved by systemic administration thing.
The content of the invention
The technical problems to be solved by the invention are in view of the shortcomings of the prior art, there is provided one kind is used to promote skin healing
Pharmaceutical composition, it includes muscarinic acceptor blocker and anticholinesterase.The pharmaceutical composition, which is applied to, to be had
The individual (including humans and animals) of skin wound so that new granulation tissue is thicker, collagen content is higher, epidermis healing rate compared with
It hurry up, and without obvious toxic-side effects.By pharmaceutical composition preparation of the invention for promoting the medicine of skin healing can be preferable
The healing of promotion epidermis, and without obvious toxic-side effects, there is preferable application prospect.
Therefore, the invention provides a kind of pharmaceutical composition for being used to promote skin healing, it includes M-ChR resistance
Disconnected agent and anticholinesterase.
According to the present invention, in described pharmaceutical composition, the muscarinic acceptor blocker and anticholinesterase
Mass ratio is 1:(100-2000)；It is preferred that the mass ratio of the muscarinic acceptor blocker and anticholinesterase is 1:
(200-600)；It is more highly preferred to, the mass ratio of the muscarinic acceptor blocker and anticholinesterase is 1:500.
In the present invention, the muscarinic acceptor blocker include anisodamine, the plant extracts containing anisodamine and Ah
One or more in tropine.The anticholinesterase includes one in neostigmine, Pyridostigmine Bromide and eserine
Kind is a variety of.
In the present invention, preferably the mass ratio of neostigmine and anisodamine is 1:(250-2000).
In the present invention, preferably the mass ratio of neostigmine and atropine is 1:(500-2000).
In the present invention, preferably the mass ratio of Pyridostigmine Bromide and anisodamine is 1:(100-500).
In the present invention, preferably the mass ratio of Pyridostigmine Bromide and atropine is 1:(200-600).
Present invention also offers a kind of aforementioned pharmaceutical compositions to prepare the application in being used to promote the medicine of skin healing.
In the present invention, the promotion skin healing include promoting surgical site infections wound healings, promote anastomotic healing with
And at least one of skin trauma wound healing caused by sharp instrument or blunt.It is preferred that the promotion skin healing is promotion surgery
Post operation wound healing promotes anastomotic healing.
Brief description of the drawings
Illustrate the present invention below in conjunction with accompanying drawing.
Fig. 1 is the union of wounded skin situation photo for the treatment of group's (medication group) and control rats.
Fig. 2 is the relative wound areas comparison curves for the treatment of group's (medication group) and control rats skin；*P<0.05, * * P
<0.01, medication therapy groups are compared with control group.
Fig. 3 is the pathological study microphoto for the treatment of group's (medication group) and control group skin wound.
Fig. 4 is the Masson coloration result microphotos for the treatment of group's (medication group) and control rats skin wound tissue.
Fig. 5 is the hydroxyproline content in sham-operation group, treatment group's (medication group) and control rats skin wound tissue
Variation diagram；**P<0.01, model experiment group is compared with normal group；#P<0.05, medication therapy groups are compared with control group.
Fig. 6 is the HE coloration result microphotos of the liver for the treatment of group's (medication group) and control rats, kidney and small intestine.
Embodiment
To make the present invention easier to understand, the present invention is described in detail below in conjunction with embodiment and accompanying drawing, these realities
Apply example only serve it is illustrative, it is not limited to application of the invention.Agents useful for same, instrument or utensil of the present invention are except special
Illustrate that outer is conventional medical agent, instrument or utensil.
Muscarinic receptor blocking agent can block the muscarinic type on the effector cell that is dominated of cholinergic nerve after section
Acceptor, there is relaxation visceral smooth muscle, the secretion for releasing smooth muscle spasm, suppressing salivary gland, sweat gland, stomach and intestine gland etc., release fan
Walk suppression of the nerve to heart, relaxation iris scrapes the about effect such as flesh, excited respiratory center.Anisodamine is planted for China's special product Solanaceae
A kind of alkaloid extracted in thing Tangut Anisodus Radix, it is generally called " 654 ", its natural product is referred to as " 654-1 ", Synthetic artifact claims " 654-2 ".
This medicine is muscarinic receptor blocking agent, and effect is similar to atropine or slightly weak, has obvious periphery cholinolytic effect, can make
The smooth muscle relaxation of spasm, and vasopasm (especially capilary) can be released, improve microcirculation, while there is analgesic activity,
But the effect expanded pupil and suppress body of gland (such as salivary gland) secretion is weaker, and seldom causes central excitation symptom.
The indication of clinical anisodamine includes：(1) vertebral disc infection：Such as the coccus meningitis of Fulminantmeningitis
(meningococal meningitis), toxic dysentery etc. (need to share) with antibacterials；(2) circulated caused by vasopasm and embolism
Obstacle：Cerebral thrombosis, cerebral infarction, paralysis, cerebral angiospasm, angioneurotic headache, thromboangiitis obliterans etc.；
(3) smooth muscle spasm：Gastric ulcer, duodenal ulcer, bile duct, ductus pancreaticus, angina caused by ureter stone；(4) various nerves
Bitterly：Such as trigeminal neuralgia, sciatica；(5) dizziness；(6) fundus oculi disease：Central retinitis, primary view
Membranochromic pigments denaturation, arteria retina thrombus etc.；(7) sudden deafness；New acupuncture is coordinated to treat other deaf (low dose of caves
Position injection)；(8) be also used for organophosphorus poisoning, but effect not as atropine it is good；9. it is configured to eye drops to can be used for because of ciliary muscle convulsion
Pseudo-myopia caused by contraction；(10) it is used for vagal excitatory and increases caused slow arrhythmia.
Anticholinesterase is that one kind can be combined with cholinesterase, and suppresses the medicine of cholinesterase activity, and it is acted on
It is the acetylcholine accumulation for discharging cholinergic nerve endings, shows muscarinic and choline-like effect enhancing and play excited courage
The effect of alkali acceptor.Neostigmine is quaternary ammonium compound, has the function that reversible inhibition cholinesterase activity, makes acetylcholine
It is able to accumulate in synapses, so as to extend and strengthen the effect of the cholinergic of acetylcholine.
As a kind of anticholinesterase, the clinical indication of neostigmine includes：(1) myasthenia gravis is treated；It is inverse
Turn the neuromuscular blockade effect of non-depolarization neuromuscular blocking drug；(2) glaucoma is treated, reduces intraocular pressure；3. paralytic intestines obstruct
Resistance and postoperative urine retention；(4) snake venom (Nervous toxicity) poisoning and fugutoxin poisoning.
So far, also it is not used to promote skin trauma to be cured on muscarinic acceptor blocker and anticholinesterase
The report of conjunction.But surprisingly, the present inventor studies discovery, by muscarinic acceptor blocker and choline
Esterase inhibitor use in conjunction can be obviously promoted the healing of experimental skin trauma.Especially, will by muscarine by
Body blocking agent combines the medicine for promoting skin healing with anticholinesterase, can obtain preferable skin healing effect
While fruit, mitigate respective side effect.Experiment shows that anisodamine and neostigmine are administered in combination in skin wound
Individual (including humans and animals) so that new granulation tissue is thicker, collagen content is higher, epidermis healing rate is very fast, and without bright
Aobvious toxic side effect, has no significant effect for rat diet, body weight and hepatic and renal function.The present invention is based on above-mentioned discovery and made
's.
Therefore, the present invention relates to a kind of pharmaceutical composition for being used to promote skin healing, it includes M-ChR blocking
Agent and anticholinesterase.
According to the present invention, in described pharmaceutical composition, the muscarinic acceptor blocker and anticholinesterase
Mass ratio is 1:(100-2000).It is preferred that the mass ratio of the muscarinic acceptor blocker and anticholinesterase is 1:
(200-600).It is more highly preferred to, the mass ratio of the muscarinic acceptor blocker and anticholinesterase is 1:500.
In the present invention, the muscarinic acceptor blocker be selected from anisodamine, the plant extracts containing anisodamine and Ah
One or more in tropine.The anticholinesterase is one kind in neostigmine, Pyridostigmine Bromide and eserine
It is or a variety of.
When the pharmaceutical composition in the present invention contains neostigmine and anisodamine, preferably neostigmine and anisodamine
Mass ratio be 1:(250-2000).
When the pharmaceutical composition in the present invention contains neostigmine and atropine, the preferred matter of neostigmine and atropine
Amount is than being 1:(500-2000).
When the pharmaceutical composition in the present invention contains Pyridostigmine Bromide and anisodamine, preferably Pyridostigmine Bromide and mountain Liang
The mass ratio of henbane alkali is 1:(100-500).
When the pharmaceutical composition in the present invention contains Pyridostigmine Bromide and atropine, preferably Pyridostigmine Bromide and atropine
Mass ratio be 1:(200-600).
The invention further relates to a kind of aforementioned pharmaceutical compositions to prepare the application in being used to promote the medicine of skin healing.
In the present invention, the promotion skin healing include promoting surgical site infections wound healings, promote anastomotic healing with
And at least one of skin trauma wound healing caused by sharp instrument or blunt.It is preferred that the promotion skin healing includes promoting surgery
Post operation wound healing promotes anastomotic healing.
The present invention is further directed to a kind of medicine for being used to promote skin healing containing aforementioned pharmaceutical compositions of the present invention
Thing.
It is described to be used to promote the medicine of skin healing that various administration forms be made in the present invention, such as digesting
The oral form of canal drug administration, the injection form for parenteral administration.The injection form includes intraperitoneal injection, intramuscular injection
With intravenous injection etc..
In certain embodiments of the present invention, heretofore described medicine can be above-mentioned composition of the present invention (including
Muscarinic acceptor blocker and anticholinesterase) suitable various administration forms with pharmaceutically acceptable carrier composition
Preparation, for example, the preparation for being adapted to oral form can be tablet, capsule, liquid and granule；And for example, it is adapted to injection form
Preparation can be parenteral solution or injectable powder.The preparation can be sustained release preparation.
Drug administration by injection is the preferable delivery method for being used to promote the medicine of skin healing of the invention.Therefore, originally
Medicine described in invention is preferably by above-mentioned composition of the present invention (including muscarinic acceptor blocker and anticholinesterase)
With the parenteral solution of pharmaceutically acceptable carrier composition.
In some specific embodiments of the present invention, the medicine is intramuscular injection or intraperitoneal injection parenteral solution, the pharmacy
Upper acceptable carrier is water for injection；In the parenteral solution, the concentration of the muscarinic acceptor blocker is 5-20mg/
ml；It is preferred that the concentration of the muscarinic acceptor blocker is 10mg/ml；The concentration of the anticholinesterase is 10-40 μ g/
ml；It is preferred that the concentration of the anticholinesterase is 20 μ g/ml.
In other specific embodiments of the present invention, the medicine is injection liquid in use for intravenous injection, described pharmaceutically
The carrier of receiving is injection physiological saline；In the intravenous fluid, the concentration of the muscarinic acceptor blocker is
0.1-0.4mg/ml；It is preferred that the concentration of the muscarinic acceptor blocker is 0.25mg/ml；The anticholinesterase it is dense
Spend for 0.2-0.8 μ g/ml；It is preferred that the concentration of the anticholinesterase is 0.5 μ g/ml.
In some specific embodiments of the present invention, it is administered using injection system, for zoopery medication, using abdominal cavity
Injection, 2 times a day.The dosage of the muscarinic acceptor blocker is 25mg/kg.The administration of the anticholinesterase
Dosage is 50 μ g/kg.
In other specific embodiments of the present invention, for human administration, using drip-feed or intramuscular injection, 2 times a day.
The dosage of the muscarinic acceptor blocker is 1-5mg/kg, preferably 1.7-4mg/kg, more preferably 2.7-3.8mg/
kg.The dosage of the anticholinesterase is 1.25~60 μ g/kg, more preferably preferably 1.7-15 μ g/kg, 4-8 μ
g/kg。
Oral administration is another preferable delivery method for being used to promote the medicine of skin healing of the invention.
Therefore, heretofore described medicine can also be for by above-mentioned composition of the present invention (including muscarinic acceptor blocker and choline
Esterase inhibitor) with pharmaceutically acceptable carrier made of tablet or capsule preparations etc..
In some specific embodiments of the present invention, the medicine is tablet or capsule, described pharmaceutically acceptable
Carrier is starch, dextrin and lactose etc.；In the tablet or capsule, the content of the muscarinic acceptor blocker is 10-
15mg/ grains；The content of the anticholinesterase is 0.2-0.3mg/ grains.Blocked for M-ChR used in human administration
The dosage of agent is is grown up 20-30mg/ times, and 3 times a day, the dosage of anticholinesterase used is 0.2-0.3mg/
It is secondary, 3 times a day.
Each active component that heretofore described term " pharmaceutical composition " refers to form the pharmaceutical composition is with mixture
Mode be applied to individual (including human or animal), the pharmaceutical composition can both be made mixing Tetramune and be applied to individual,
By the independent preparation for each active component for forming the pharmaceutical composition individual can be applied to after being compounded using the row that advances.
Heretofore described term " atropine " (atropine), also known as atropine sulfate or DL hyoscyamine, chemistry
Entitled α-(methylol) phenylacetic acid 8- methyl -8- azabicyclos [3,2,1] -3- monooctyl esters, chemical molecular formula C17H23NO3, its
Shown in chemical structural formula such as formula (I)；Atropine is to be extracted from plant belladonna and other plants of Solanaceae such as datura flower or henbane
A kind of alkaloid gone out, also can be artificial synthesized.
Heretofore described term " anisodamine " (Anisodamine), also known as anisodamine hydrobromate or racemization
Anisodamine；Chemical molecular formula is C17H23NO4, shown in its chemical structural formula such as formula (II)；Anisodamine is that China is special
A kind of alkaloid extracted in production plant of Solanaceae Tangut Anisodus Radix, often referred to as " 654 ", its natural product turns into " 654-1 ".Manually synthesize
Product made from method is into " 654-2 ".
Heretofore described term " neostigmine " (Neostigmine), also known as prostigmine；Neostigmine；Bromine
Neostigmine, chemical name are bromination-N, N, N- trimethyl -3- [(dimethylamino) formyloxy] puratized agricultural spray, and chemical molecular formula is
C12H19BrN2O2, shown in its chemical structural formula such as formula (III).
Heretofore described term " Pyridostigmine Bromide " (Pyridostigmine Bromide), also known as pyridinium bromide this
This bright, beautiful you or pyrrole this bright, chemical name is bromination 1- methyl -3- pyridone dimethyl carbamates, chemistry
Molecular formula is C9H13BrN2O2, shown in its chemical structural formula such as formula (IV).
During heretofore described term " relative wound areas " refers to trauma care, the wound area that measures in real time with
The ratio of wound area before treatment, it can be calculated by formula (V).
In formula (V)：
SRelativelyFor relative wound areas, it is expressed as a percentage；
StFor the wound area measured in real time, unit mm；
S0Wound area before treatment, unit mm.
It is provided by the present invention to be used to promote the pharmaceutical composition of skin healing to include muscarinic acceptor blocker and choline
Esterase inhibitor.Said composition is applied to the individual (including humans and animals) with skin wound, can newly to granulate
Tissue is thicker, collagen content is higher, epidermis healing rate is very fast, and without obvious toxic-side effects, for rat diet, body weight and liver
Renal function has no significant effect.By pharmaceutical composition preparation of the invention for promoting the medicine of skin healing preferably to promote
Enter epidermis healing, and without obvious toxic-side effects, there is preferable application prospect.
Embodiment
Embodiment 1：
1. experimental animal and reagent
(1) experimental animal is cleaning grade male SD rat, body weight 230-260g, by Military Medical Science Institute experimental animal
The heart provides.
(2) experimental drug is methyl-sulfuric acid neostigmine parenteral solution (Shanghai Xinyi Jin Zhu pharmaceutcal corporation, Ltds) and hydrochloric acid racemic
Anisodamine injection (Tianjin KingYork Amino Acid Co., Ltd.).
2. the making of Acute skin trauma model
Rat uses ether inhalation anesthesia after adaptability is fed 2 days.First back wool is pushed with electric hair clipper, then with 5%
Vulcanized sodium is de- clean by back wool.Then with iodophor disinfection field of operation, used in the nearly stern lateral ridge post both sides same area of rat back
Special card punch manufactures diameter 1.5cm 2 circular skin holostrome otch, does not injure subcutaneous fascia layer.By all rat models
Single cage is raised, and is freely fully drunk water.
3. drug therapy and sample collection
Rat model is randomly divided into joint anisodamine and neostigmine medication therapy groups (Ani+Neo) and physiological saline
Group control group (Control).Every group is further divided into postoperative 3,7,10 and 14 days time materials groups, every group of each 6 rats of time point.
Anisodamine (25mg/kg) and neostigmine (50 μ g/kg) is twice daily injected intraperitoneally in medication therapy groups, and control group gives equivalent
Physiological saline.Rats in sham-operated group 6 is set in addition.
In postoperative 3rd, 7,10 and 14 day by rat anesthesia, the holostrome away from surface of a wound edge 0.3cm centered on the surface of a wound is cut
Skin and hypodermis, two halves being cut to from center, half is affixed on to be placed on filter paper in 10% neutral formalin solution and fixed,
FFPE is standby.Remaining tissue is placed in ice physiological saline and rinsed, then is blotted with filter paper, and -80 DEG C save backup.
4. Wound healing rate determines
The observation rat surface of a wound is red and swollen daily, infect and ties unreasoning passion condition, and healing early stage, which whether there is, oozes out, bleeding, and later stage wound is cured
Conjunction and cicatrization etc..And photograph to record surface of a wound size daily, using ImagePro softwares calculate surface of a wound area, and with before medication
(the operation same day) compares, and calculates the wound healing percentage of the postoperative different time of each surface of a wound of every animal.Wound healing hundred
Divide behind rate=medication long-pending × 100% before product/medication.
5. pathological study
Take the wound tissue conventional section of FFPE, HE dyeing, the reaction of light Microscopic observation inflammatory cell and granulation tissue
Growing state.Entered in addition with Masson staining kits (Accustain Trichrome Stains, Sigma-Aldrich)
Row collagen develops the color, and evaluates healing speed and quality.
6. organize hydroxyproline (Hydroxyproline, Hyp) assay
Part cryopreserved tissue is taken to be homogenized, with hydroxyproline colorimetric reagent box (Hydroxyproline
Colorimetric assay kit, BioVision) measure wound tissue in hydroxyproline content, operation said by kit
Bright book is carried out.
7. statistical analysis
All data are represented using mean ± standard deviation, are compared between two groups and are examined progress statistical analysis with t-, more than two
Comparison use one-way analysis of variance (ANOVA), using SPSS17.0 carry out statistical analysis, take P<0.05 is to have statistics meaning
Justice.
8. interpretation of result
(1) use in conjunction anisodamine and neostigmine can be obviously promoted rat skin wound healing
Anisodamine and neostigmine treatment (medication therapy groups) are given after making rat full skin excision trauma model,
Control rats and the union of wounded skin situation of use in conjunction anisodamine and neostigmine treatment group rat are shown in Fig. 1.From Fig. 1
As can be seen that postoperative 1-3 days, saline control group and medication therapy groups rat skin wound surface have diffusate, surface of a wound periphery
There is red and swollen, basal part granulation tissue growth, but the administration group surface of a wound is dry and incrustation is more early；Postoperative 4-10 days, two groups of rats
The surface of a wound is all filled by new granulation tissue, but administration group rat edge of wound skin contraction is significantly faster than that control group；Postoperative 11-
Two groups of rat surface of a wound regions of 14d are reduced significantly, and administration group surface of a wound area is significantly less than control group.It can be seen that use in conjunction mountain
Hyoscyamine and neostigmine can be obviously promoted rat acute skin wound healing.
(2) influence of use in conjunction anisodamine and neostigmine to Wound healing rate
The influence of use in conjunction anisodamine and neostigmine to the default Wound healing rate of rat skin is as shown in Figure 2.Fig. 2
It is the relative wound areas comparison curves for the treatment of group's (medication group) and control rats skin, the smaller explanation skin of relative wound areas
The default Wound healing rate of skin is higher.Figure it is seen that the 3rd of use in conjunction anisodamine and neostigmine treatment group rat the,
5th, the relative wound areas of 7,10 and 14 days is significantly less than control group, it is seen that use in conjunction anisodamine and neostigmine treatment
The Wound healing rate of the 3rd, 5,7,10 and 14 day of group rat is all remarkably higher than control group, the statistically significant (P of difference<0.01
Or P<0.05).Compared with saline control group, use in conjunction anisodamine and neostigmine significantly can promote rat skin to create
Recover from injury and close, shorten wound healing time.
(3) pathological study of union of wounded skin
After postoperative different time takes rat skin wound granulation tissue and surrounding skin carries out HE dyeing, tissue disease is carried out
The pathological study result of Neo-Confucianism analysis, use in conjunction anisodamine and neostigmine treatment group Skin Wound Healing In Rats
As shown in Figure 3.
From figure 3, it can be seen that postoperative 3d：There are the granulation tissue of new life and the infiltration of inflammatory cell under each group scab；Medicine
Thing treatment group is thicker than the newborn granulation tissue layer of control group, and fibroblast is more；Postoperative 7d：Two groups of new life epidermises are obvious
Thicken, the obvious hyperplasia of granulation tissue, intradermal is shown in that thin vessels grow into and find substantial amounts of fibroblast, and the hyperplasia of blank group
Degree is significantly stronger than control group；Postoperative 10d：New capillary vessel is more in two groups of neoplastic skin tissues, collagen arrangement disorder.Control
Treatment group epidermis heals substantially, and the surface of a wound is not yet completely covered in blank group epidermis；Postoperative 14d：Two composition fibrocytes are less,
Treatment group's major part surface of a wound forms marshalling new life collagen, and cell differentiation is obvious, wound healing, the newborn collagen arrangement of control
It is still disorderly.Therefore, the Wound Contraction of medication therapy groups and epithelialization is faster than control group again.
(4) influence of use in conjunction anisodamine and neostigmine to wound tissue collagen content
The collagen content of rat wound tissue, Masson dyeing displays are assessed using Masson dyeing and Hyp assays
Collagen contents such as Fig. 4 in use in conjunction anisodamine and neostigmine group rat and control rats skin wound tissue
It is shown.From fig. 4, it can be seen that the 3rd after wound, the collagen contents of the rat Wound Defect of 5,7,10 and 14 days gradually increase
Add, and the collagen content for the treatment of group is above control group in Each point in time.
Hydroxyl dried meat in use in conjunction anisodamine and neostigmine treatment group rat and control rats skin wound tissue
Histidine content is as shown in Figure 5.From fig. 5, it can be seen that Hyp content is (1.79 ± 0.49) μ g/ in rat normal skin tissue
Mg organizes (n=5).Control group and treatment group are the 3rd and 7 day after wound, and Hyp contents significantly reduce in granulation tissue, still
The Hyp contents for the treatment of group are apparently higher than control group (P<0.05).Compared with saline control group, use in conjunction anisodamine and Xin Si
The bright collage synthesis that can significantly promote rat skin wound tissue.
(5) influence of use in conjunction anisodamine and neostigmine to each internal organs of skin trauma rat
After making rat skin trauma model, use in conjunction anisodamine and neostigmine are treated 14 days.Pass through blood biochemistry
Detection and histopathological analysis, determine the influence of use in conjunction anisodamine and neostigmine to liver, kidney and enteron aisle, tie
Fruit is as shown in Table 1 and Table 2.
The liver function index of the skin trauma rat model medication 14 days of table 1
The renal function index of the skin trauma rat model medication 14 days of table 2
| Experiment packet | CREA(μmol/L) | UA(μmol/L) | UREA(mmol/L) |
| Normal group | 24.60±3.26 | 134.80±66.81 | 5.50±0.47 |
| Control group | 21.93±1.95 | 87.45±22.3 | 4.08±0.42 |
| Medication group | 21.03±3.13 | 111.75±56.75 | 3.81±0.41 |
As can be seen from Table 1 and Table 2, blood biochemistry testing result shows that use in conjunction anisodamine and neostigmine treatment are big
Total serum protein, albumin, transaminase, bilirubin, alkaline phosphatase, creatinine, urea and uric acid of the mouse skin trauma after 14 days
, without significant difference, show that medicinal application has no significant effect to rat Liver and kidney function Deng all with normal rat and control rats.
HE coloration results are as shown in fig. 6, from fig. 6, it can be seen that the liver of medication therapy groups and control group, kidney and small intestine
Histopathological structures it is normal, occur without obvious infringement.Prompt use in conjunction anisodamine and neostigmine treatment rat skin
Skin wound is without obvious toxic-side effects.
The foregoing is only presently preferred embodiments of the present invention, be not intended to limit the invention, it is all the present invention spirit and
Within principle, any modification, equivalent substitution and improvements made etc., it should be included in the scope of the protection.
Claims (3)
1. a kind of application of pharmaceutical composition in the medicine for being used for promoting trauma skin to heal is prepared, described pharmaceutical composition bag
Include the quality of muscarinic acceptor blocker and anticholinesterase, the anticholinesterase and muscarinic acceptor blocker
Than for 1:500, wherein, the anticholinesterase is neostigmine, and the muscarinic acceptor blocker is anisodamine.
2. application according to claim 1, it is characterised in that the promotion trauma skin healing includes promoting surgical operation
Afterwards wound healing, promote anastomotic healing and sharp instrument or blunt caused by least one of skin trauma wound healing.
3. application according to claim 2, it is characterised in that the promotion trauma skin healing is promotion surgical site infections
Wound healing promotes anastomotic healing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510379777.8A CN104940934B (en) | 2015-07-01 | 2015-07-01 | A kind of pharmaceutical composition and its application for being used to promote skin healing |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510379777.8A CN104940934B (en) | 2015-07-01 | 2015-07-01 | A kind of pharmaceutical composition and its application for being used to promote skin healing |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104940934A CN104940934A (en) | 2015-09-30 |
| CN104940934B true CN104940934B (en) | 2018-02-09 |
Family
ID=54156351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510379777.8A Active CN104940934B (en) | 2015-07-01 | 2015-07-01 | A kind of pharmaceutical composition and its application for being used to promote skin healing |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104940934B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105943537B (en) * | 2016-06-28 | 2019-03-19 | 顾万清 | Compouneded anisodamine neostigmine sustained release tablets and preparation method thereof |
| CN114099490A (en) * | 2021-12-30 | 2022-03-01 | 温州医科大学附属第二医院（温州医科大学附属育英儿童医院） | Function of rivastigmine in preparing medicine for promoting survival of ischemic overlong random skin flap |
| CN114533732A (en) * | 2022-01-24 | 2022-05-27 | 范德里希(上海)生物科技有限公司 | Application of compound anisodamine injection in treating scald |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2419093A (en) * | 2004-10-12 | 2006-04-19 | Ernir Snorrason | Acetylcholinesterase inhibitors for the treatment of skin |
| CN101856498A (en) * | 2009-04-10 | 2010-10-13 | 中国人民解放军第二军医大学 | Anti-septic shock medicine compound and application thereof |
| CN102580099A (en) * | 2011-10-20 | 2012-07-18 | 中国人民解放军第二军医大学 | Composition for resisting ischemia reperfusion injury and preparation method and application thereof |
| CN102836157A (en) * | 2012-09-12 | 2012-12-26 | 高尔医药科技(上海)有限公司 | Application of neostigmine hyoscyamine in preparation of medicine for treating acute cerebral ischemic injury |
| CN103110627A (en) * | 2011-11-16 | 2013-05-22 | 高尔医药科技(上海)有限公司 | Application of medicinal composition |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7635709B2 (en) * | 2002-09-26 | 2009-12-22 | The United States Of America As Represented By The Department Of Veterans Affairs | Compositions and methods for bowel care in individuals with chronic intestinal pseudo-obstruction |
-
2015
- 2015-07-01 CN CN201510379777.8A patent/CN104940934B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2419093A (en) * | 2004-10-12 | 2006-04-19 | Ernir Snorrason | Acetylcholinesterase inhibitors for the treatment of skin |
| CN101856498A (en) * | 2009-04-10 | 2010-10-13 | 中国人民解放军第二军医大学 | Anti-septic shock medicine compound and application thereof |
| CN102580099A (en) * | 2011-10-20 | 2012-07-18 | 中国人民解放军第二军医大学 | Composition for resisting ischemia reperfusion injury and preparation method and application thereof |
| CN103110627A (en) * | 2011-11-16 | 2013-05-22 | 高尔医药科技(上海)有限公司 | Application of medicinal composition |
| CN102836157A (en) * | 2012-09-12 | 2012-12-26 | 高尔医药科技(上海)有限公司 | Application of neostigmine hyoscyamine in preparation of medicine for treating acute cerebral ischemic injury |
Non-Patent Citations (1)
| Title |
|---|
| 山莨菪碱用于创面换药69 例报告;杜桂华 等;《药学实践杂志》;19981231;第16卷(第1期);第17-18页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104940934A (en) | 2015-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108348577B (en) | Mussel mucin product and application thereof in inhibiting skin inflammation | |
| CN101267831B (en) | Compositions and methods for promoting hemostasis and other physiological activities | |
| CN110876760B (en) | Skin external composition with wound healing promoting and/or scar repairing effects | |
| CN104940934B (en) | A kind of pharmaceutical composition and its application for being used to promote skin healing | |
| CN102327419A (en) | External use medicine for treating wound healing | |
| ES2340603T3 (en) | BACTERIAL CULTURE WITH SUPPRESSING EFFECT OF THE DEVELOPMENT OF DERMATITIS AND ACCELERATOR OF WOUND AND PRODUCT CICATRIZATION USING IT. | |
| CN101507731A (en) | Chitosan uterus-neck antibiotic film and preparation method thereof | |
| CN102038733B (en) | Externally-used traditional Chinese medicine for treating hypertrophic scar and preparation method thereof | |
| CN108030950A (en) | A kind of wound dressing of dispeling scar | |
| CN107809999A (en) | For treating the composition of lesion tissue | |
| CN111803488B (en) | Application of atractylenolide II in preparation of anti-renal fibrosis medicine and anti-renal fibrosis medicine | |
| JP2009269904A (en) | Herbal medicinal composition for curing external wound and bedsore and method of manufacturing medicine from the composition | |
| CN103705910B (en) | A kind of Ziconotide injection hypodermic implant and preparation method thereof | |
| JP2019503335A (en) | Use of Dimethylamino Micheliolide | |
| US20070207215A1 (en) | Medicament On The Basis Of Honey, Preparation And Use Thereof | |
| CN112823799A (en) | Preparation method and application of pharmaceutical composition for treating knee osteoarthritis | |
| CN102697835B (en) | The topical agent for the treatment of disease of skin | |
| US20070128293A1 (en) | Extrapallial fluid of molluscs, methods of obtaining same, formulation and use thereof | |
| CN104490760A (en) | Preparation method and application of capsaicin-collagen sponge | |
| CN107007621A (en) | It is a kind of that there is pharmaceutical composition for the treatment of skin injury effect and its preparation method and application | |
| CN103948617B (en) | Pharmaceutical composition for treating and preventing adhesion after abdominal operation | |
| CN107296954A (en) | A kind of laminin Wound surface protection film | |
| CN102302636A (en) | Medicament for treating burn and preparation method thereof | |
| RU2529412C2 (en) | Method for preperitoneal block following median postoperative ventral hernioplasty | |
| RU2808182C1 (en) | Method of treating burns in animals |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230303 Address after: No. 188, Meishan Meiliang Road, Binhu District, Wuxi City, Jiangsu Province, 214000 Patentee after: Wuxi round road medical science and Technology Research Institute Co.,Ltd. Address before: Editorial Department of Chinese Journal of Hepatobiliary Surgery, No. 28, Fuxing Road, Haidian District, Beijing, 100853 Patentee before: Gu Wanqing |
|
| TR01 | Transfer of patent right |