CN104940934A - Pharmaceutical composition used for promoting skin healing and application thereof - Google Patents
Pharmaceutical composition used for promoting skin healing and application thereof Download PDFInfo
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Abstract
The invention relates to a pharmaceutical composition used for promoting skin healing. The pharmaceutical composition used for promoting the skin healing comprises a muscarinic receptor blocker and a cholinesterase inhibitor. After the pharmaceutical composition used for promoting the skin healing is applied to individuals (comprising human and animals) with a skin wound, newly born granulation tissues are thicker, collagen content is high, epidermis healing speed is high, no obvious toxic or side effect is produced, and no obvious influence is produced to diet, weight and hepatic and renal functions of a rat. The pharmaceutical composition provided by the invention can be used for well promoting the skin healing and produces no obvious toxic or side effect, so that the pharmaceutical composition used for promoting the skin healing has a good application prospect.
Description
Technical field
The invention belongs to skin healing pharmaceutical technology sectors, relating to a kind of for promoting pharmaceutical composition and the application thereof of skin healing.
Background technology
Skin is the first barrier of body defenses environmental stimuli and damage.The cause injury damage of skin that the factor causes and each tissue of mechanicalness will cause the situations such as microorganism invasion, moisture and protein-loss, endocrine and immune dysfunction, and severe patient can cause body dead.In numerous disease therapeutic process, as required surgical operation also can cause serious skin and internal organs wound.From clinical practice experience in the past, in the agglutination of wound or surgical patient wound surface, otch and various anastomotic stoma, as occurred, healing is not good causes wound surface or infection of incisional wound, disruption of wound, as not goodly in the healing of alimentary tract anastomosis mouth occur that intestinal leaks, pancreas leaks or the complication such as gallbladder leakage, the lighter can reduce the actual effect of operative treatment, and severe one then directly can threaten the life security of patient.Therefore, promote that the treatment of various wound healing plays vital effect for the life and health of the mankind.
Small size wound for skin surface adopts external adjuvant to improve wound healing at present.According to material, medical dressing can be divided into natural class dressing, synthesis class dressing and combine dressing.The dressing of the traditional plant such as gauze, binder is the natural class dressing of a most widely used class up to now, can absorb wound exudate, prevents the generation of local hydrops, but shortcoming is easily dry and easy adhesion wound.Synthesis class external dressing is a kind of dressing that research is many at present, and it is of a great variety, mainly utilizes high molecular special nature, as film property, antibiotic property etc., for wound surface provides the wet environment of appropriate cell growth; The bearing hydrocolloid dressing that such as gelatin, pectin and carboxymethyl cellulose are mixed, has good mechanical property, but may pollute wound surface after absorbing a large amount of exudate; By the aerogel dressing that water-soluble high-molecular material or monomer whose are processed to form through special process, good biocompatibility, absorbability is strong, can with wound close adhesion, reach the aseptic effect of resistance bacterium, but easily dry hardening, cause sense of discomfort.Combine dressing is generally multilamellar dressing, skin is macromolecular material, and internal layer is the combined dressing that biomaterial is formed, and combines the macromolecular material resistance bacterium feature of breathing freely and the good histocompatibility of biomaterial, there is good water penetration and breathability, but without anastalsis; These methods easily cause wound dehydrates, are unfavorable for that epithelial cell is creeped, and dressing easily and wound is sticky joins, and easily causes mechanical damage, unfavorable wound healing when changing dressings; And for large surgical operation, particularly the internal organs, deep tissue and the skin trauma that cause of thoracic and abdominal operation is without any effect, and therefore the wound healing of deep tissue may need the effect that just can be reached wound healing by systemic administration thing.
Summary of the invention
Technical problem to be solved by this invention is for the deficiencies in the prior art, and provide a kind of for promoting the pharmaceutical composition of skin healing, it comprises muscarinic acceptor blocker and cholinesterase inhibitor.This pharmaceutical composition is applied to the individuality (comprising humans and animals) with skin wound, such that new granulation tissue is thicker, collagen content is higher, epidermis healing rate is very fast, and without obvious toxic-side effects.By pharmaceutical composition of the present invention prepare for promoting that the medicine of skin healing can promote that epidermis heals preferably, and without obvious toxic-side effects, there is good application prospect.
For this reason, the invention provides a kind of for promoting the pharmaceutical composition of skin healing, it comprises muscarinic acceptor blocker and cholinesterase inhibitor.
According to the present invention, in described pharmaceutical composition, the mass ratio of described muscarinic acceptor blocker and cholinesterase inhibitor is 1:(100-2000); The mass ratio of preferred described muscarinic acceptor blocker and cholinesterase inhibitor is 1:(200-600); More preferred, the mass ratio of described muscarinic acceptor blocker and cholinesterase inhibitor is 1:500.
In the present invention, described muscarinic acceptor blocker comprises Anisodamine, containing one or more in the plant extract of Anisodamine and atropine.Described cholinesterase inhibitor comprise in neostigmine, pyridostigmine bromide and physostigmine one or more.
In the present invention, the mass ratio of preferred neostigmine and Anisodamine is 1:(250-2000).
In the present invention, preferred neostigmine and atropinic mass ratio are 1:(500-2000).
In the present invention, the mass ratio of preferred pyridostigmine bromide and Anisodamine is 1:(100-500).
In the present invention, preferred pyridostigmine bromide and atropinic mass ratio are 1:(200-600).
Present invention also offers the application of a kind of aforementioned pharmaceutical compositions in the medicine for the preparation of promotion skin healing.
In the present invention, described promotion skin healing comprises at least one in the skin trauma wound healing promoting that surgical site infections wound healing, promotion anastomotic healing and sharp instrument or blunt cause.Preferred described promotion skin healing is for promoting surgical site infections wound healing or promoting anastomotic healing.
Accompanying drawing explanation
Below in conjunction with accompanying drawing, the present invention is described.
Fig. 1 is the union of wounded skin situation photo for the treatment of group (medication group) and control rats.
Fig. 2 is the relative wound areas comparison curves for the treatment of group (medication group) and control rats skin; * P<0.05, * * P<0.01, medication therapy groups compares with matched group.
Fig. 3 is the pathological study microphotograph for the treatment of group (medication group) and matched group skin wound.
Fig. 4 is the Masson coloration result microphotograph for the treatment of group (medication group) and control rats skin wound tissue.
Fig. 5 is the hydroxyproline content variation diagram in sham operated rats, treatment group (medication group) and control rats skin wound tissue; * P<0.01, model experiment group compares with normal group; #P<0.05, medication therapy groups compares with matched group.
Fig. 6 is the HE coloration result microphotograph of the liver for the treatment of group (medication group) and control rats, kidney and small intestinal.
Detailed description of the invention
For making the present invention easier to understand, describe the present invention in detail below in conjunction with embodiment and accompanying drawing, these embodiments only play illustrative effect, are not limited to range of application of the present invention.Agents useful for same of the present invention, instrument or utensil are conventional medical agent, instrument or utensil unless otherwise indicated.
Muscarinic receptor blocker can block the muscarinic receptor after joint on the effector cell arranged of cholinergic nerve, has lax visceral smooth muscle, removes smooth muscle spasm, suppresses the secretion of salivary gland, sweat gland, gastrointestinal gland etc., removes vagus nerve and scrape the about effect such as flesh, excited respiratory center to the suppression of heart, lax iris.Anisodamine is a kind of alkaloid extracted in China's special product plant of Solanaceae Radix Anisodi Tangutici, and common name " 654 ", its natural product are called " 654-1 ", Synthetic artifact claims " 654-2 ".This medicine is muscarinic receptor blocking agent, act on similar to atropine or slightly weak, there is obvious periphery cholinolytic effect, the smooth muscle loosening of spasm can be made, and vasospasm (especially blood capillary) can be removed, improve microcirculation, there is analgesic activity simultaneously, but the effect that platycoria and suppression body of gland (as salivary gland) are secreted is more weak, and seldom causes central excitation symptom.
The indication of clinical Anisodamine comprises: (1) vertebral disc infection: meningitis as coccus in Fulminantmeningitis (epidemic cerebrospinal meningitis), toxic dysentery etc. (need share with antibacterials); (2) circulatory disturbance that causes of vasospasm and thromboembolism: cerebral thrombosis, cerebral infarction, paralysis, cerebral vasospasm, angioneurotic headache, thromboangiitis obliterans etc.; (3) smooth muscle spasm: the angor that gastric ulcer, duodenal ulcer, bile duct, ductus pancreaticus, ureter stone cause; (4) various neuralgia: as trigeminal neuralgia, sciatica etc.; (5) dizziness; (6) fundus oculi disease: central serous chorioretinopathy, primary pigmentary degeneration of the retina, arteria retina thrombosis etc.; (7) sudden deafness; Coordinate new acupuncture can treat other deafnesses (low dose of acupoint injection therapy); (8) also for organophosphate poisoning, but effect is good not as atropine; 9. be mixed with the pseudomyopia that eye drop can be used for because ciliary spasm causes; (10) caused bradyarrhythmia is increased for vagal excitatory.
Cholinesterase inhibitor is that a class can be combined with acetylcholine esterase, and suppresses the medicine of cholinesterase activity, and its effect is that the acetylcholine that cholinergic nerve endings is discharged is piled up, and performance muscarinic and choline-like effect strengthen and play the effect of excited cholinoceptor.Neostigmine is quaternary ammonium compound, has the effect of reversible inhibition cholinesterase activity, acetylcholine is able in synapses accumulation, thus extends and strengthen the cholinergic effect of acetylcholine.
As a kind of cholinesterase inhibitor, the clinical indication of neostigmine comprises: (1) treatment myasthenia gravis; Reverse the neuromuscular blockade effect of non-depolarization neuromuscular blocking drug; (2) treat glaucoma, reduce intraocular pressure; 3. paralytic ileus and postoperative urine retention; (4) snake venom (Nervous toxicity) is poisoning poisoning with tetraodontoxin.
Up to now, also not about muscarinic acceptor blocker and cholinesterase inhibitor for promoting the report of skin wound healing.But unexpectedly, the present inventor studies discovery, muscarinic acceptor blocker and cholinesterase inhibitor use in conjunction can be promoted significantly the healing of experimental skin trauma.Especially, by be combined the medicine for promoting skin healing with cholinesterase inhibitor by muscarinic acceptor blocker, while obtaining good skin healing effect, respective side effect can be alleviated.Test shows, Anisodamine and neostigmine co-administered in the individuality (comprising humans and animals) with skin wound, make that new granulation tissue is thicker, collagen content is higher, epidermis healing rate is very fast, and without obvious toxic-side effects, rat diet, body weight and hepatic and renal function are had no significant effect.The present invention makes based on above-mentioned discovery just.
Therefore, the present invention relates to a kind of for promoting the pharmaceutical composition of skin healing, it comprises muscarinic acceptor blocker and cholinesterase inhibitor.
According to the present invention, in described pharmaceutical composition, the mass ratio of described muscarinic acceptor blocker and cholinesterase inhibitor is 1:(100-2000).The mass ratio of preferred described muscarinic acceptor blocker and cholinesterase inhibitor is 1:(200-600).More preferred, the mass ratio of described muscarinic acceptor blocker and cholinesterase inhibitor is 1:500.
In the present invention, described muscarinic acceptor blocker is selected from Anisodamine, containing one or more in the plant extract of Anisodamine and atropine.Described cholinesterase inhibitor is one or more in neostigmine, pyridostigmine bromide and physostigmine.
When the pharmaceutical composition in the present invention contains neostigmine and Anisodamine, the mass ratio of preferred neostigmine and Anisodamine is 1:(250-2000).
When the pharmaceutical composition in the present invention contains neostigmine and atropine, preferred neostigmine and atropinic mass ratio are 1:(500-2000).
When the pharmaceutical composition in the present invention contains pyridostigmine bromide and Anisodamine, the mass ratio of preferred pyridostigmine bromide and Anisodamine is 1:(100-500).
When the pharmaceutical composition in the present invention contains pyridostigmine bromide and atropine, preferred pyridostigmine bromide and atropinic mass ratio are 1:(200-600).
The invention still further relates to the application of a kind of aforementioned pharmaceutical compositions in the medicine for the preparation of promotion skin healing.
In the present invention, described promotion skin healing comprises at least one in the skin trauma wound healing promoting that surgical site infections wound healing, promotion anastomotic healing and sharp instrument or blunt cause.Preferred described promotion skin healing comprises promotion surgical site infections wound healing or promotes anastomotic healing.
The present invention also relates to a kind of medicine for promoting skin healing containing aforementioned pharmaceutical compositions of the present invention further.
In the present invention, described for promoting that the medicine of skin healing can make various administration form, such as, for the oral form of digestive tract administration, the injection form for parenteral administration.Described injection form comprises lumbar injection, intramuscular injection and intravenous injection etc.
In certain embodiments of the present invention, medicine described in the present invention can be the preparation of the applicable various administration form that above-mentioned composition of the present invention (comprising muscarinic acceptor blocker and cholinesterase inhibitor) forms with pharmaceutically acceptable carrier, such as, the preparation being applicable to oral form can be tablet, capsule, liquid and granule; And for example, the preparation being applicable to injection form can be injection or injectable powder.Described preparation can be slow releasing preparation.
Drug administration by injection is of the present invention for promoting the preferred delivery method of the medicine of skin healing.Therefore, medicine described in the present invention is preferably the injection be made up of above-mentioned composition of the present invention (comprising muscarinic acceptor blocker and cholinesterase inhibitor) and pharmaceutically acceptable carrier.
In specific embodiments more of the present invention, described medicine is intramuscular injection or lumbar injection injection, and described pharmaceutically acceptable carrier is water for injection; In described injection, the concentration of described muscarinic acceptor blocker is 5-20mg/ml; The concentration of preferred described muscarinic acceptor blocker is 10mg/ml; The concentration of described cholinesterase inhibitor is 10-40 μ g/ml; The concentration of preferred described cholinesterase inhibitor is 20 μ g/ml.
In other specific embodiments of the present invention, described medicine is injection liquid in use for intravenous injection, and described pharmaceutically acceptable carrier is injection normal saline; In described intravenous fluid, the concentration of described muscarinic acceptor blocker is 0.1-0.4mg/ml; The concentration of preferred described muscarinic acceptor blocker is 0.25mg/ml; The concentration of described cholinesterase inhibitor is 0.2-0.8 μ g/ml; The concentration of preferred described cholinesterase inhibitor is 0.5 μ g/ml.
In specific embodiments more of the present invention, adopt injection system administration, for zoopery medication, adopt lumbar injection, every day 2 times.The dosage of described muscarinic acceptor blocker is 25mg/kg.The dosage of described cholinesterase inhibitor is 50 μ g/kg.
In other specific embodiments of the present invention, for human administration, adopt intravenous drip or intramuscular injection, every day 2 times.The dosage of described muscarinic acceptor blocker is 1-5mg/kg, is preferably 1.7-4mg/kg, is more preferably 2.7-3.8mg/kg.The dosage of described cholinesterase inhibitor is 1.25 ~ 60 μ g/kg, is preferably 1.7-15 μ g/kg, is more preferably 4-8 μ g/kg.
Oral administration is of the present invention for promoting another preferred delivery method of the medicine of skin healing.Therefore, medicine described in the present invention also can be tablet for being made up of above-mentioned composition of the present invention (comprising muscarinic acceptor blocker and cholinesterase inhibitor) and pharmaceutically acceptable carrier or capsule preparations etc.
In specific embodiments more of the present invention, described medicine is tablet or capsule, and described pharmaceutically acceptable carrier is starch, dextrin and lactose etc.; In described tablet or capsule, the content of described muscarinic acceptor blocker is 10-15mg/ grain; The content of described cholinesterase inhibitor is 0.2-0.3mg/ grain.Dosage for human administration's muscarinic acceptor blocker used is adult 20-30mg/ time, and every day 3 times, the dosage of cholinesterase inhibitor used is 0.2-0.3mg/ time, every day 3 times.
Term described in the present invention " pharmaceutical composition " refers to that each active component forming this pharmaceutical composition is applied to individuality (comprising human or animal) in the mode of mixture, this pharmaceutical composition both can have been made mixture goods and be applied to individuality, also can by the independent preparation of each active component forming this pharmaceutical composition carry out before use composite after be applied to individuality.
Term described in the present invention " atropine " (atropine), also be called atropine sulfate or DL hyoscyamine, chemical name is α-(methylol) phenylacetic acid 8-methyl-8-azabicyclo [3,2,1]-3-monooctyl ester, chemical molecular formula is C
17h
23nO
3, its chemical structural formula is as shown in formula I; Atropine is a kind of alkaloid extracted from plant Semen daturae and other plants of Solanaceae such as Flos Daturae or hyoscyami etc., also can synthetic.
Term described in the present invention " Anisodamine " (Anisodamine), is also called Anisodamine hydrobromate or racemization anisodamine hydrobromide; Chemical molecular formula is C
17h
23nO
4, its chemical structural formula is as shown in formula II; Anisodamine is a kind of alkaloid extracted in China's special product plant of Solanaceae Radix Anisodi Tangutici, and normal abbreviation " 654 ", its natural product become " 654-1 ".The product obtained with artificial synthesis becomes " 654-2 ".
Term described in the present invention " neostigmine " (Neostigmine), is also called prostigmine; Neostigmine; Neostigmine bromide, chemical name is bromination-N, and N, N-trimethyl-3-[(dimethylamino) formyloxy] puratized agricultural spray, chemical molecular formula is C
12h
19brN
2o
2, its chemical structural formula is as shown in formula III.
Term described in the present invention " pyridostigmine bromide " (Pyridostigmine Bromide), also this this this bright of you or pyrrole bright, beautiful of pyridinium bromide is called, chemical name is bromination 1-methyl-3-pyridone dimethyl carbamate, and chemical molecular formula is C
9h
13brN
2o
2, its chemical structural formula is as shown in formula IV.
Term described in the present invention " relative wound areas " refers in trauma care process, and the ratio of the wound area measured in real time and the wound area before treating, it can calculate by through type (V).
In formula (V):
S
relativelyfor relative wound areas, be expressed as a percentage;
S
tfor the wound area measured in real time, unit is mm;
S
0wound area before treatment, unit is mm.
Provided by the present invention for promoting that the pharmaceutical composition of skin healing comprises muscarinic acceptor blocker and cholinesterase inhibitor.Said composition is applied to the individuality (comprising humans and animals) with skin wound, can make that new granulation tissue is thicker, collagen content is higher, epidermis healing rate is very fast, and without obvious toxic-side effects, rat diet, body weight and hepatic and renal function are had no significant effect.By pharmaceutical composition of the present invention prepare for promoting that the medicine of skin healing can promote that epidermis heals preferably, and without obvious toxic-side effects, there is good application prospect.
Embodiment
Embodiment 1:
1. laboratory animal and reagent
(1) laboratory animal is cleaning grade male SD rat, and body weight 230-260g is provided by Military Medical Science Institute's Experimental Animal Center.
(2) experimental drug is methyl-sulfuric acid neostigmine injection (Xinyi, Shanghai Jin Zhu pharmaceutcal corporation, Ltd) and anisodamine (Tianjin KingYork Amino Acid Co., Ltd.).
2. the making of Acute skin trauma model
Rat, after adaptability feeds 2 days, uses ether inhalation anesthesia.First push back wool with electric hair clipper, then with 5% sodium sulfide by de-for back wool clean.Then with iodophor disinfection field of operation, manufacture 2 circular skin holostrome otch of diameter 1.5cm at the special card punch of rat back nearly buttocks lateral ridge post both sides same area, do not injure subcutaneous fascia layer.All rat model list cages are raised, freely fully drinks water.
3. Drug therapy and sample collection
Rat model is divided at random associating Anisodamine and neostigmine medication therapy groups (Ani+Neo) and normal saline group matched group (Control).Often group is further divided into postoperative 3,7,10 and 14 day time and draws materials group, often organizes each time point 6 rats.Medication therapy groups twice lumbar injection Anisodamine (25mg/kg) every day and neostigmine (50 μ g/kg), matched group gives normal saline.Establish rats in sham-operated group 6 in addition.
In the postoperative 3rd, within 7,10 and 14 days, by rat anesthesia, to cut centered by wound surface apart from the full thickness skin of wound surface edge 0.3cm and subcutaneous tissue, be cut to two halves from central authorities, half is affixed on neutral formalin solution filter paper being placed in 10% and fixes, and paraffin embedding is for subsequent use.Remaining tissue is placed in the rinsing of ice normal saline, then blots with filter paper, and-80 DEG C save backup.
4. Wound healing rate measures
Observe every day rat wound surface red and swollen, infect and knot unreasoning passion condition, healing in early days with or without oozing out, hemorrhage, later stage wound healing and cicatrization etc.And every day Taking Pictures recording wound surface size, utilize ImagePro computed in software wound surface area, and compare with (performing the operation the same day) before medication, calculate the wound healing percentage rate of the postoperative different time of each wound surface of every animal.× 100% is amassed before long-pending/medication after wound healing percentage rate=medication.
5. pathological study
Get the section of paraffin-embedded wound tissue routine, HE dyes, the growing state of the reaction of light Microscopic observation inflammatory cell and granulation tissue.Carry out collagen colour developing with Masson staining kit (Accustain Trichrome Stains, Sigma-Aldrich) in addition, evaluate healing speed and quality.
6. organize hydroxyproline (Hydroxyproline, Hyp) assay
Get part cryopreserved tissue and carry out homogenate, measure the hydroxyproline content in wound tissue with hydroxyproline colorimetric reagent box (Hydroxyprolinecolorimetric assay kit, BioVision), operate and undertaken by test kit description.
7. statistical analysis
All data acquisitions mean ± standard deviation represents, compare between two groups and carry out statistical analysis with t-inspection, comparison more than two adopts one factor analysis of variance (ANOVA), utilizing SPSS17.0 to carry out statistical analysis, getting P<0.05 for there being statistical significance.
8. interpretation of result
(1) use in conjunction Anisodamine and neostigmine can obviously promote rat skin wound healing
Give Anisodamine and neostigmine treatment (medication therapy groups) after making rat full skin excision trauma model, the union of wounded skin situation of control rats and use in conjunction Anisodamine and neostigmine treatment group rat is shown in Fig. 1.As can be seen from Figure 1, postoperative 1-3 days, saline control group and medication therapy groups rat skin wound surface all have transudate, and wound surface periphery occurs red and swollen, and basilar part granulation tissue grows, but administration is formed face drying and formed a scab comparatively early; Postoperative 4-10 days, two groups of rat wound surface are all filled by new granulation tissue, but administration group rat edge of wound contraction of skin is obviously faster than matched group; Postoperative 11-14d two groups of rat wound surface regions all significantly reduce, and administration is formed face area and is significantly less than matched group.Visible, use in conjunction Anisodamine and neostigmine can obviously promote rat acute skin wound healing.
(2) use in conjunction Anisodamine and neostigmine are on the impact of Wound healing rate
Use in conjunction Anisodamine and neostigmine are on the impact of the default Wound healing rate of rat skin as shown in Figure 2.Fig. 2 is the relative wound areas comparison curves for the treatment of group (medication group) and control rats skin, and the default Wound healing rate of relative wound areas less explanation skin is higher.As can be seen from Figure 2, the 3rd, 5,7 of use in conjunction Anisodamine and neostigmine treatment group rat, the relative wound areas of 10 and 14 days is all significantly less than matched group, the 3rd, 5,7 of visible use in conjunction Anisodamine and neostigmine treatment group rat, the Wound healing rate of 10 and 14 days is all significantly higher than matched group, and difference has statistical significance (P<0.01 or P<0.05).Compared with saline control group, use in conjunction Anisodamine and neostigmine can promote rat skin wound healing significantly, shorten wound healing time.
(3) pathological study of union of wounded skin
After postoperative different time gets rat skin wound granulation tissue and surrounding skin carries out HE dyeing, carry out histopathological analysis, the pathological study result of use in conjunction Anisodamine and neostigmine treatment group Skin Wound Healing In Rats as shown in Figure 3.
As can be seen from Figure 3, postoperative 3d: have newborn granulation tissue and the infiltration of inflammatory cell under each group blood crusts; Medication therapy groups is thicker than the granulation tissue layer of the new life of matched group, and fibroblast is more; Postoperative 7d: two groups of newborn epidermises obviously thicken, the obvious hypertrophy of granulation tissue, and intradermal is shown in that thin vessels is grown into and finds a large amount of fibroblasts, and the hyperplasia degree of blank group is obviously better than matched group; In postoperative 10d: two groups of neoplastic skin tissue, new capillary vessel is more, collagen arrangement disorder.Treatment group epidermal area heals substantially, blank group epidermal area flap coverage not yet completely; Postoperative 14d: two composition fibrocytes are less, and treatment group major part wound surface forms the newborn collagen of marshalling, and cell differentiation is obvious, wound healing, and the newborn collagen arrangement of contrast is still disorderly.Therefore, medication therapy groups Wound Contraction and again epithelization all faster than matched group.
(4) use in conjunction Anisodamine and neostigmine are on the impact of wound tissue collagen content
Utilize Masson to dye and the collagen content of Hyp assay assessment rat wound tissue, Masson dyeing shows collagen contents in use in conjunction Anisodamine and neostigmine group rat and control rats skin wound tissue as shown in Figure 4.As can be seen from Figure 4, after wound, the collagen contents of rat Wound Defect of the 3rd, 5,7,10 and 14 day increases gradually, and the collagen content for the treatment of group at each time point all higher than matched group.
Hydroxyproline content in use in conjunction Anisodamine and neostigmine processed group rat and control rats skin wound tissue as shown in Figure 5.As can be seen from Figure 5, in rat normal skin tissue, the content of Hyp is that (1.79 ± 0.49) μ g/mg organizes (n=5).Matched group and treatment group are after wound the 3rd and 7 days, and in granulation tissue, Hyp content all significantly reduces, but the Hyp content for the treatment of group is apparently higher than matched group (P<0.05).Compare with saline control group, use in conjunction Anisodamine and neostigmine can promote the collage synthesis of rat skin wound tissue significantly.
(5) use in conjunction Anisodamine and neostigmine are on the impact of each internal organs of skin trauma rat
After making rat skin trauma model, use in conjunction Anisodamine and neostigmine treat 14 days.Detected and histopathological analysis by blood biochemistry, determine that use in conjunction Anisodamine and neostigmine are on the impact of liver, kidney and intestinal, result as shown in Table 1 and Table 2.
The table 1 skin trauma rat model medication liver function index of 14 days
The table 2 skin trauma rat model medication renal function index of 14 days
| Experiment grouping | CREA(μmol/L) | UA(μmol/L) | UREA(mmol/L) |
| Normal group | 24.60±3.26 | 134.80±66.81 | 5.50±0.47 |
| Matched 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 display use in conjunction Anisodamine and the neostigmine treatment total serum protein of rat skin wound after 14 days, albumin, transaminase, bilirubin, alkali phosphatase, creatinine, carbamide and uric acid etc. all with normal rat and control rats without significant difference, show that medicinal application has no significant effect rat Liver and kidney function.
As shown in Figure 6, as can be seen from Figure 6, the histopathological structures of the liver of medication therapy groups and matched group, kidney and small intestinal is normal, occurs without obvious damage for HE coloration result.Prompting use in conjunction Anisodamine and neostigmine treatment rat skin wound are without obvious toxic-side effects.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (9)
1., for promoting a pharmaceutical composition for skin healing, it comprises muscarinic acceptor blocker and cholinesterase inhibitor.
2. pharmaceutical composition according to claim 1, is characterized in that, in described pharmaceutical composition, the mass ratio of described muscarinic acceptor blocker and cholinesterase inhibitor is 1:(100-2000).
3. pharmaceutical composition according to claim 2, is characterized in that, the mass ratio of described muscarinic acceptor blocker and cholinesterase inhibitor is 1:(200-600).
4. pharmaceutical composition according to claim 3, is characterized in that, the mass ratio of described muscarinic acceptor blocker and cholinesterase inhibitor is 1:500.
5. according to the pharmaceutical composition in claim 1-4 described in any one, it is characterized in that, described muscarinic acceptor blocker comprises Anisodamine, containing one or more in the plant extract of Anisodamine and atropine; Described cholinesterase inhibitor comprise in neostigmine, pyridostigmine bromide and physostigmine one or more.
6. pharmaceutical composition according to claim 5, is characterized in that,
Neostigmine: the mass ratio of Anisodamine is 1:(250-2000);
Neostigmine: atropinic mass ratio is 1:(500-2000);
Pyridostigmine bromide: the mass ratio of Anisodamine is 1:(100-500);
Pyridostigmine bromide: atropinic mass ratio is 1:(200-600).
7. one kind as the pharmaceutical composition in claim 1-6 as described in any one for the preparation of promote skin healing medicine in application.
8. application according to claim 7, is characterized in that, described promotion skin healing comprises at least one in the skin trauma wound healing promoting that surgical site infections wound healing, promotion anastomotic healing and sharp instrument or blunt cause.
9. application according to claim 8, is characterized in that, described promotion skin healing is for promoting surgical site infections wound healing or promoting anastomotic healing.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| 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 |
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| Publication number | Publication date |
|---|---|
| CN104940934B (en) | 2018-02-09 |
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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 |