Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art and provide a kind of easy to use, safe and reliable, cost is low, nonirritant, effect obviously, determined curative effect and the medicine and preparation method thereof of the dispeling scar of treatment and rehabilitation effect is arranged, to alleviate cicatrix patient's misery, satisfy the needs of health care beauty treatment.
The object of the present invention is achieved like this:
A kind of medicine of dispeling scar is characterized in that: be prepared from by weight by following raw materials:
5 parts of 50 parts of Borneolum Syntheticums of 100 parts of Fructus Bruceaes of Semen Persicae
200 parts of 30 parts of glycerol of 5 parts of alkalium of Camphora
5 parts of 5 parts of glyceryl monostearates of 100 parts of octadecanol of vaseline.
A kind of medicine of dispeling scar is characterized in that: be prepared from by weight by following raw materials:
50 parts of 300 parts of Borneolum Syntheticums of 500 parts of Fructus Bruceaes of Semen Persicae
600 parts of 300 parts of glycerol of 50 parts of alkalium of Camphora
50 parts of 50 parts of glyceryl monostearates of 500 parts of octadecanol of vaseline.
A kind of preparation method of medicine of above-mentioned dispeling scar is characterized in that its preparation method is as follows:
1, squeezing Semen Persicae and Fructus Bruceae are got oil, add Borneolum Syntheticum, Camphora grinding, get mixed liquor;
2, take by weighing vaseline, glyceryl monostearate, octadecanol, the mixed liquor that adds step 1 carries out heating and melting in pot;
3, take by weighing glycerol and alkalium mixing mixing batter;
4, with the gains of step 3 to the emulsifying pot, again with the gains of step 2 to the emulsifying pot, emulsifying;
5, cooling, check, canned.
In step 5, with the mastic embedding in sebific duct or other satisfactory packaging materials.
The present invention has following good effect:
One, clinical verification of the present invention is reported as follows:
(1), purpose:,, and conclude with its effect of definite understanding, safety and untoward reaction for the present invention is enlarged checking.
(2), case is selected:
1, indication: the cicatrix that reasons such as burn, scald, carbuncle sore, wound stay, hypertrophic cicatrix and keloid etc.
2, diagnostic criteria:
(1), have burn, scald, carbuncle sore, wound medical history person, and have cicatrix body constitution person;
(2), the skin horizontal direction or the vertical direction of wound surface convalescent period or the appearance of reparation back are soaked into the hard tuberosity or the speckle that exceed skin of propagation;
(3), skin lesion is with pruritus or pigmentation.
3, include standard in:
(1), all possess above-mentioned (1), (2) or three persons;
(2), the age was at 8 years old to 65 years old.
4, exclusion standard:
(1), cicatrix patient wound does not heal or the infected of festering is arranged;
(2), actute infection heat pyrexia patient is arranged;
(3), on inspection confirm to suffer from tumor, heavy and angiopathy, metabolic disease, hemorrhage, hepatopathy, nephropathy etc.;
(4), suffer from psychotic disorder and can not finish the observer;
(5), gestation or women breast-feeding their children are to this medicine allergy sufferers below 8 years old and the over-65s person age;
(6), all standards of including in that do not meet, not medication in accordance with regulations can't be judged that curative effect or data are not congruent to affect the treatment or safety judgement person.
(3), observation of curative effect:
1, safety is observed
(1) general health check-up project; (2) hematuria routine; (3) liver, kidney function test.
2, observation of curative effect
(1) speckle or scleroma size variation; (2) cicatrix firmness change; (3) the calm pigment alteration of cicatrix; (4) antipruritic; (5) recovery from dysfunction situation.
(4), methods of clinical observation:
1, fixed 3 experimental units of clinical trial, each unit example number is no less than 40 examples (30 examples are organized in treatment, matched group 10 examples).Experimenter's separating tests group and matched group.
2, administrated method: medicine of the present invention and control drug (blank) secondary every day, divide early, directly embrocate this cream on cicatrix evening, do not need the external application gauze, exposes treatment, continuous 30 days is a course of treatment, two courses of treatment of clinical observation are as efficacy determination.
3, points for attention: (1) wound not healing person is avoided usefulness; (2) avoid inlet, avoid and be strayed into eyes; (3) infant is avoided usefulness; (4) irritated as using this product to occur, pain takes place, itch, pimple, local edema etc. can reduce consumption or stop using; (5) deposit and to locate in the cool place.
(5), curative effect determinate standard:
1, produce effects: cicatrix attenuation, the obvious deliquescing of quality.
2, effective: cicatrix is attenuation slightly, but the gargalesthesia disappearance, pigment shoals.
3, invalid: treatment back symptom variation is little.
(6), result of the test:
Treat cicatrix patient 100 examples altogether, hypertrophic cicatrix 41 examples wherein, keloid 59 examples, cicatrix 162 places take place in 100 routine patients altogether, wherein facial 83 places, trunk 20 places, extremity 59 places.Age is at 8~56 years old, male's 44 examples.Women's 56 examples.Pathogenic factor is seen (78/100) with burn and other wound more.
Matched group 30 examples, male's 12 examples, women's 18 examples.Hypertrophic cicatrix 17 examples, keloid 13 examples.
Table 1 treatment group and matched group Comparison of therapeutic
Table 2 hypertrophic cicatrix and keloid Comparison of therapeutic
Keloid (n=59) |
17 |
30 |
12 |
47 |
79.66 |
(7), discuss
1, treats hypertrophic cicatrix and keloid at present ideal Therapeutic Method and medicine are seldom arranged.The clinical effective medicine (effective percentage 81.00%) that provides is provided in the present invention, obviously is better than the contrast treatment, for the clinical treatment cicatrix has increased a powerful measure.
2, hypertrophic cicatrix and keloid therapeutic outcome are approaching, the statistical procedures no significant difference.
3, external of the present invention is safe and effective, the non-stimulated and side effect of most patients, and only small number of patients can have temporary local pruritus.
Characteristics of the present invention: (1) is easy to use; (3) be not subjected to the restriction of cicatrization time; (4) formed the restriction of reason hardly.
Two, Pharmacodynamic test of active extract data of the present invention
(1) the present invention causes the influence of granulation hyperplasia model mice to medical silica-gel
Summary: cause local proliferation of fibrous tissue for the mouse subcutaneous injection medical silica-gel, simulate cicatrization from pathology, smeared the present invention on this basis continuous one month, granulation dissipates in the visible skin corium of microscopically, collagen fiber reduce, loose connective tissue and appendages of skin demutation point out this medicine that scar tissue is had the diffusing long-pending effect of certain softening the hard mass.
1, purpose: cicatrix mainly shows as fibroblast proliferation on pathology, forms a large amount of collagen fiber, and the appendages of skin reduce and lose normal organizational structure.Because of not seeing the bibliographical information that the cicatrix animal pattern is arranged, laboratory once all can not make the local cicatrix that forms of mice with several different methods such as scald, chemical burns, so the method that adopts medical silica-gel to be injected under the animal skins causes proliferation of fibrous tissue, the pathology of simulation cicatrix change, and smear on this basis to be subjected to reagent to observe this medicine to " cicatrix " histological influence.
2, medicine:
(1) the present invention and excipient (forming) by glycerol, white vaseline, octadecanol, glyceryl monostearate.
(2) chromatographic silica gel: white powder, be made into 20% aseptic suspension solution, use for subcutaneous injection.
3, animal: white mice, male, body weight 24-28g is provided by Experimental Animal Center.Conventional feed is fed, and drinking-water is not limit, 22-25 ℃ of experiment room temperature, relative humidity 50-60%.
4, grouping and method:
Grouping: 80 animals are divided into 2 groups at random, 40 every group.
(1) excipient matched group (model group): 0.1g/d * 30 local topicals.
(2) of the present invention group: 0.1g/d * 30 local topicals.
Method:
1) 20% silicone fluid in white mice back subcutaneous injection 0.5ml/ only.
2) get 5 animals every group of 2,4,6,8 weekends of injection behind the silica gel at every turn, draw neck to put to death, get the skin at injection silica gel position and do the pathology cut sections for microscopic examination, observe its histology and change, to determine whether to form " cicatrix " model.
3) formed model (, confirming 6-8 week can form model behind the injection silica gel) as confirming, then begun by the group medicine for external application continuous one month through giving test repeatedly.
4) animal cropping secondary weekly, and respectively at last every group of local skin of getting 5 animals around second week behind the coating, the at every turn to do the pathology cut sections for microscopic examination, to observe the effect of this medicine.
5, result or conclusion: give continuous month of model mice partial smearing the present invention, histopathologic examination, find that this medicine can promote that granulation dissipates in the skin corium, collagen fiber reduce, make loose connective tissue and appendages of skin demutation, point out this medicine that scar tissue is had certain softening the hard mass removing food stagnancy effect.
(2) antiinflammatory action test of the present invention---agar method
Summary: subcutaneous injection agar, cause the rat chronic nonspecific inflammation, be coated with outward with the present invention, the trend that alleviates agar granuloma weight is arranged in continuous 14 days.
1, purpose: give rat skin lower injection agar, can cause the local granuloma similar, observe behind coating the present invention influence to granuloma weight to clinical later stage pathological change.
2, medicine:
(1) the present invention and excipient (forming) by glycerol, white vaseline, octadecanol, glyceryl monostearate.
(3) agar: be made into 2% solution with NS during experiment, scalding is standby.
3, animal: male Wistar rat, body weight 170-200g is provided by Experimental Animal Center.22-25 ℃ of experiment room temperature, conventional feed, amount of drinking water is not limit.
4, grouping and method:
Grouping: 16 animals are divided into 2 groups at random, 8 every group.
(1) excipient matched group (model group): glycerol etc. are coated with for 0.2g/ time * 14 innings.
(2) of the present invention group: be coated with for 0.2g/ time * 14 innings.
Method: each Mus back cropping of experiment proxima luce (prox. luc), about 4 * the 5cm2 of area, next day is the sterile working under the shallow fiber crops of ether, in the agar solution 2ml of back center line subcutaneous injection 2%, and smears relative medicine by group, once a day, continuous 14 days, dissected animal, separate granuloma agar embryo in 15th, press the 100g body weight and calculate weight in wet base, learn by statistics and handle the difference that compares medication group and model control group.
5, result or conclusion: give the continuous application of rat 14 days with the present invention, can alleviate the granulomatous weight of agar, illustrate that this medicine has the trend that suppresses its chronic nonspecific inflammation under this dosage.
(3) function of promoting blood circulation to disperse blood clots of the present invention---Mice Auricle microcirculation test
Summary: be coated with the present invention outward for Mice Auricle, can increase local microvascular open number, the expansion blood capillary is outstanding with venule, increases red cell velocity in the venule, points out this medicine that certain function of promoting blood circulation to disperse blood clots is arranged.
1, purpose: examine under a microscope the intravital mouse Auricle Microcirculation and change, be subjected to the function of promoting blood circulation to disperse blood clots of reagent in order to reflection.
2, medicine and instrument:
(1) the present invention and excipient (forming) by glycerol, white vaseline, octadecanol, glyceryl monostearate.
(2) barium sulfide, pentobarbital sodium.
(3) microscope, micrometer, cold light source.
3, animal: Kunming mouse, male and female are regardless of, and female for not producing and not having pregnantly, body weight 24-27g is provided by Experimental Animal Center.Conventional feed is fed, and drinking-water is not limit, 22-25 ℃ of experiment room temperature, relative humidity 50-60%.
4, grouping and method:
Grouping: 20 animals are divided into 2 groups at random, 10 every group.
(1) excipient matched group: 0.1g/ ear * 2 such as glycerol innings are coated with.
(2) of the present invention group: 0.1g/ ear * 2 innings are coated with.
Method:
1) experiment is preceding 2 days, will be tried right side of mice auricle dorsal part hair with 8% barium sulfide solution and slough.
2) experiment was smeared and was subjected to the reagent secondary by drafting dosage the morning on the same day, midfeather 4 hours, and carry out microcirculation detect half an hour behind the last coating.
3) give mice through intraperitoneal anesthesia with 0.3% pentobarbital sodium solution 0.15ml/10g (45mg/kg) immediately before the detection.
4) animal is lain on the back be fixed on the Mus plate, placement coverslip under the auricle of right side, and, auricle is easily pasted mutually with slide at its periphery dropstone wax oil, be horizontal level.
5) under cold light source, observe with microscope.
6) selecting mouse ear profile lateral border blood capillary, is the object of observation with arteriole and the vein of caliber 6-8um, observes the variation of erythrocyte fluidised form and flow velocity in the vary in diameter of the open number of blood capillary, arteriole, venule and the blood capillary respectively.
5, result or conclusion:
(1) to the influence of the open number of auricle blood capillary: the present invention can increase microvascular open number.
(2) to the influence of auricle microvascular diameter: the present invention has the microvascular effect of expansion, especially with the work that act as to venule.
(3) to the influence of auricle blood capillary fluidised form and flow velocity: with the excipient matched group mutually specific energy accelerate red cell velocity.
(4) the present invention can promote the microcirculation of Mice Auricle, points out this medicine that significant function of promoting blood circulation to disperse blood clots is arranged.
(4) antipruritic test of the present invention
Summary: the present invention can obviously resist the effect of itching of causing of phosphoric acid tissue.
1, purpose: understand the histamine phosphate of Cavia porcellus local skin contact variable concentrations by this experiment after, this medicine is to the influence of its itch-threshold.
2, medicine:
(1) the present invention and excipient (forming) by glycerol, white vaseline, octadecanol, glyceryl monostearate.
(2) histamine phosphate: white powder, the solution that is mixed with variable concentrations with normal saline is used for experiment.
3, animal: Cavia porcellus, male and female are regardless of, and female for not producing and not having pregnantly, body weight 300-330g is provided by Experimental Animal Center.Conventional feed is fed, and drinking-water is not limit, 22-25 ℃ of experiment room temperature, relative humidity 50-60%.
4, grouping and method:
Grouping: 16 Cavia porcelluss are divided into 2 groups at random, 8 every group.
(1) excipient matched group: 0.1g pawl * 2 externals.
(2) of the present invention group: 0.1g/ pawl * 2 externals.
Method: in the experiment proxima luce (prox. luc), give the cropping of the right back instep of each Cavia porcellus portion, smear by group in the cropping position and correspondingly tried thing once next day, after half an hour, rub the part to minority oozing of blood point is arranged with Coarse Mesh Gauze, repaste is smeared relative medicine once, and beginning in 10 minutes after administration, drip 0.01% the 50ul/ of histamine phosphate pawl respectively with microsyringe at each agents area, later on every three minutes, dripping successively with the position that concentration increases progressively is 0.02%, 0.03%, 0.04% again ... the histamine phosphate of equivalent is till Cavia porcellus occurring and later licking metapedes.Giving the total amount of the histamine phosphate that each animal dripped respectively in period with this section is itch-threshold.And the itch-threshold of each animal in every group carried out statistical procedures, between organizing relatively.
5, result or conclusion: smear the present invention to Cavia porcellus, the itch-threshold of its animal is apparently higher than the excipient matched group.Illustrate that this medicine has certain itching-relieving action.
Three, sanitary index testing result of the present invention:
Test item |
Unit |
Testing result (average) |
Limit value |
Plumbous (Pb) |
mg/kg |
<0.08 |
≤40 |
Hydrargyrum (Hg) |
mg/kg |
0.004 |
≤1 |
Arsenic (As) |
mg/kg |
<0.01 |
≤10 |
Bacterial population |
CFU/mL |
<10 |
≤1000 |
Fungi count |
CFU/mL |
<10 |
≤100 |
Staphylococcus aureus |
|
Do not detect |
Must not detect |
Test item |
Unit |
Testing result (average) |
Limit value |
Bacillus pyocyaneus |
|
Do not detect |
Must not detect |
Demodicid mite lives |
|
Do not detect |
Must not detect |
Four, Semen Persicae in the present invention's prescription is the mature seed kernel of peach, and its property hardship, sweet, flat has blood circulation promoting and blood stasis dispelling, and the moistening for dryness and softening hard mass effect can be impelled carbuncle, the softening dissipation of cicatrix; Fructus Bruceae, property hardship, cold, but external softening the hard mass removing food stagnancy, removing blood stasis with potent drugs is capable to loose the wart of dispelling, cicatrix tuberosity; Borneolum Syntheticum, the hot perfume (or spice) of property is walked string, and external has reducing swelling and alleviating pain, except that rotten antipruritic, the swollen merit of kind dissipating blood stasis; Fructus Bruceae and Borneolum Syntheticum play blood circulation promoting and blood stasis dispelling with Semen Persicae, and the softening the hard mass removing food stagnancy is anticorrosion antipruritic, disappear to control the nodular effect of cicatrix; Camphora, property is hot loose ward off turbid, the external parasite killing that can dehumidify, eliminating stasis to stop pain is changed the detumescence that stagnates, and uses alkalium in addition, property is salty, bitter, warm, but external softening the hard mass removing food stagnancy piece, blood stasis dispelling blood, killing parasites for relieving itching, each medicine is played promoting blood circulation and breaking stagnation altogether, and the softening the hard mass removing food stagnancy is eliminated pruritus, make softening, the detumescence of cicatrix and hypertrophic cicatrix, the effect of putrefaction removing itching relieving.Use glycerol, vaseline, octadecanol and glyceryl monostearate to be substrate, suitable viscosity and stretchability are arranged, also unlikely its character of change of its stable in properties, dry sterilization can not become sour, nonirritant, on skin, can form occlusive and cover, impel the hydration of keratodermatitis, make cicatrix softening, in the hope of playing the crust softening and shedding, reach the rehabilitation effect.Take a broad view of prescription, all medicines cooperatively interact, and play promoting blood circulation and breaking stagnation altogether, and the softening the hard mass removing food stagnancy is changed the scar itching-relieving action, can be used for cicatrix and keloidal rehabilitation that a variety of causes causes.