CN1456170A - External applied medicine composition containing vitamin B - Google Patents
External applied medicine composition containing vitamin B Download PDFInfo
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- CN1456170A CN1456170A CN 03127032 CN03127032A CN1456170A CN 1456170 A CN1456170 A CN 1456170A CN 03127032 CN03127032 CN 03127032 CN 03127032 A CN03127032 A CN 03127032A CN 1456170 A CN1456170 A CN 1456170A
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Abstract
An exterior-applied medicine for preventing and treating the local injury of skin or skin lesion contains VB12 or its derivatives, and one or more pharmacologically acceptable carriers or exipients.
Description
The affiliated field of invention
The present invention relates to vitamin B
12And derivant, particularly relate to and contain vitamin B
12Or derivatives thereof, and the skin of one or more pharmaceutically acceptable carriers or excipient or mucosa externally-applied medicinal composition.The invention further relates to the application of said pharmaceutical composition in prevention and treatment various skin local damage or pathological changes.
The background of invention
Life entity will be subjected to various environmental effects inevitably.These influences comprise the radiation of irradiation, ground surface and the building of cosmic ray and solar ultraviolet, and the various physical stimulations such as variations in temperature in the living environment; Also comprise the absorption of foreign substance in trace contaminant in the air or the food, and the various chemical stimulations such as intrusion of the biotic factor of invisible virus, antibacterial, fungus etc.Because intravital complexity of machine and strong protection mechanism, make living body biological can overcome these infringements and survived.Yet, when body protective mechanism can not be resisted these infringements, will cause organizing accordingly the particularly damage and the pathological changes of skin histology.For example, these skin injurys comprise radiodermatitis, radioactivity pigmentation, solar dermatitis, anaphylaxis or specificity eczema, tinea cruris and tinea manus and pedis, and herpes zoster etc.
Current, lonizing radiation, nucleic generally are used for many fields such as industry, agricultural, medical treatment and military affairs.Owing to the extensive use of lonizing radiation, nucleic, inevitably some direct or indirect contactee is caused the radiation injury of in various degree damage, particularly skin.In case damage forms, and is easy to involve subcutaneous tissue and causes secondary infection, forms prolonged intractable ulcer of not healing, its long-term biological effect obviously overweights general scald (burning) and hinders.
In addition, at some in particular cases, for example using the radiation method to treat under the situation of tumor tumor locus of being treated even the ionizing radiation that will be exposed to about 3000-5000 rad (30-50 gray(Gy)).In order to keep radiological dose every day during the whole treatment; in the radiation destroys tumor cell; also usually can cause the destruction of epidermal basal cell and dermal microvascular endothelial cell; cause microvascular obstruction of damaged part and closure; and then cause erythema, blister and the ulcer of damaged part; and the fibrosis of surrounding tissue, stay the chronic radioactive skin injury that is difficult to cure at last.
Moreover, some metabolic disease for example diabetes and skin aging usually with skin pruritus, dryness seborrheic dermatitis and the xerosis cutis of refractory with chap etc.
At present disclose some and be used to prevent and treat the medicine of the radiation injury that causes behind the tumour radiotherapy, for example dimethyl sulfoxide, cystamine, S-2-(3-aminopropyl amino) D2EHDTPA ethyl ester etc.Yet these chemicalses mostly are prevention and the treatments (for example being used to protect bone marrow stem cell) that is used for general radiation sickness.Particularly, these medicines all have than maxicell toxicity and the more serious effect of paying, and directly use so often be difficult on the human body.
With regard to radiation-induced skin injury particularly with regard to the acute skin injury, previously used Therapeutic Method mainly comprises: n of high dose oral potassium iodide or vitamin E, local use paraffin, zinc stearate, zinc oxide and animal oil, and the acidifying hydrogen peroxide of local coating and contain the ointment etc. of aloe juice.For example, United States Patent (USP) 4,384 discloses pimple squama type and the inflammatory dermatosis method of using the treatment of hydrochloric acid two phenoxy group esters to comprise radiodermatitis for No. 000.United States Patent (USP) 5,538 discloses for No. 740 and to have used the medicine composite for curing that contains Limax secretions to comprise the method for the various skin disease of radiodermatitis, solar dermatitis and burn.United States Patent (USP) 5,266 discloses for No. 318 and to have used the Aloe glue and the mixture of allantoin and Essential lavender oil to treat the method for radiation injury of skin.United States Patent (USP) 6,538 discloses for No. 740 and to have used the pollen extract and the non-saponification mixture partly of vegetable oil to improve the microcirculatory method of skin histology.
Yet, do not see as yet that up to now use is with vitamin B
12As the pharmaceutical composition prevention of primary activity composition and the report of various skin diseases such as radiotherapy dermatitis, solar dermatitis and burn.
The purpose of invention
An object of the present invention is to provide a kind of pharmaceutical composition that is used to prevent and treat local skin damage and pathological changes, be characterised in that said pharmaceutical composition is by vitamin B basically
12Form with one or more pharmaceutically acceptable carriers or excipient.
According to a preferred embodiment of the invention, said pharmaceutical composition also can contain Radix Oenotherae erythrosepalae oil.
According to a preferred embodiment of the invention, said pharmaceutical composition also can contain gentamycin.
According to a preferred embodiment of the invention, said pharmaceutical composition also can contain one or more other active component with collaborative or assosting effect.
According to a preferred embodiment of the invention, damage of wherein said local skin and pathological changes can be radioactivity or inactive.
According to a preferred embodiment of the invention, damage of said local skin and pathological changes are selected from radiodermatitis, radiation burn, radioactivity pigmentation, common burn, solar dermatitis, specificity eczema, tinea manus and pedis and tinea cruris, seborrheic dermatitis, and the xerosis cutis relevant with dysbolismus and skin aging, chap, pruritus and shallow table ulcer.
According to a preferred embodiment of the invention, said pharmaceutical composition is a local topical administration.
According to a preferred embodiment of the invention, the dosage form of said pharmaceutical composition is selected from ointment, solution, Emulsion, paste and gel.
Another object of the present invention provides vitamin B
12Be used for preventing application with the medicine of radiotherapy and damage of on-radiation local skin or pathological changes in production.
According to a preferred embodiment of the invention, damage of said local skin and pathological changes are selected from radiodermatitis, radiation burn, radioactivity pigmentation, common burn, solar dermatitis, specificity eczema, tinea manus and pedis and tinea cruris, seborrheic dermatitis, and the xerosis cutis relevant with dysbolismus and skin aging, chap, pruritus and shallow table ulcer.The detailed description of invention
The present invention relates to vitamin B
12Or derivatives thereof particularly relates to and contains vitamin B
12Or derivatives thereof, and the skin of one or more pharmaceutically acceptable carriers or excipient or mucosa externally-applied medicinal composition.The invention further relates to the application of said pharmaceutical composition in prevention and treatment various skin local patholoic change and damage.
Vitamin B
12(be called cyanogen cobalt VB again
12) be a kind of human and animal's important vitamin, be generally used for treating pernicious anemia and peripheral nervous inflammation.Vitamin B
12It also is a kind of feed additive that is used to promote growth of animal.In this manual, term vitamin B
12Be meant the coordination compound that all are formed by cobalt and porphyrin ring, particularly comprise the cobalamine compounds that is replaced by corresponding residue or its salt of cobalamin, hydroxocobalamin, mecobalamin and 5 '-deoxyadenosine cobalt amine etc.
Body is when accepting the nonionic radiation irradiation in various sources, for example tumour patient is when accepting radiation treatment, or nuclear power factory, nuclear tests base or medical radiation course generation radioactivity are when revealing, usually may cause the relevant personnel's radiation injury, particularly directly be exposed to the radiation injury of the local skin under the radioactive source.The morning and evening of taking place according to damage and the order of severity different, radiation injury generally can be divided into acute and chronic injury, and I, II, the damage of III degree.Since the powerful penetration power of radioactive source, radiation injury usually can cause be different from common scald or burn than the hypodermic damage in deep, thereby bring difficulty to the treatment of these damages.For example, usually occur in early days after the irradiation narrow, the tortuous so that obliteration of the swelling of vascular endothelial cell gland plastochondria, lumen of vessels, cause local blood capillary circulatory disturbance finally to cause fibrosis.Visible clinically xerosis cutis, desquamation and leather sample become.Up to now, still do not treat the ideal medicament of radiation skin injury.
The inventor finds vitamin B by lot of experiments in the long-term practice of being engaged in the radiation injury preventing and controlling
12The prevention of radiation skin injury and treatment had make us the effect that is difficult to expect.Based on this discovery, the inventor has successfully prepared with vitamin B finally through groping repeatedly
12External preparation for skin pharmaceutical composition for the primary activity composition.Further also be surprisingly found out that in the further investigation at us, this pharmaceutical composition not only can be used for the prevention and the treatment of radiation skin injury effectively, but also can be used for some other dermatosis for example solar dermatitis, specificity eczema, tinea manus and pedis and tinea cruris, seborrheic dermatitis effectively, and the xerosis cutis relevant with dysbolismus and skin aging, chap, former or dermopathic prevention of secondary and treatment such as pruritus and shallow table ulcer.
Therefore, an object of the present invention is to provide a kind of pharmaceutical composition that is used to prevent and treat the local skin pathological changes, be characterised in that said pharmaceutical composition contains vitamin B
12, and one or more pharmaceutically acceptable carrier or excipient.
As the primary activity composition of pharmaceutical composition of the present invention, vitamin B
12Comprise all by the coordination compound that metallic element cobalt and porphyrin ring form, particularly comprise the cobalamine compounds that is replaced by corresponding residue of cobalamin, hydroxocobalamin, mecobalamin and 5 '-deoxyadenosine cobalt amine etc. or their salt.In general, vitamin B in the pharmaceutical composition of the present invention
12Content be approximately every 10ml solution and contain 20-80mg.Because of the multiple fibrosis event of radiation injury after effect far away requires ointment to be the gala shape is good, (seeing embodiment 1 for details).
According to a preferred embodiment of the invention, said pharmaceutical composition also can contain Radix Oenotherae erythrosepalae oil.Radix Oenotherae erythrosepalae oil is the vegetable oil that derives from the wild plant Radix Oenotherae erythrosepalae, and it has convergence, improves the local circulation effect.Radix Oenotherae erythrosepalae oil commonly used clinically at present is applied to prevent and treat coronary heart disease, thrombosis cardiovascular disease etc.Therefore the main supplementary element that usually is used as pharmaceutical composition of the present invention.The content of Radix Oenotherae erythrosepalae oil is approximately every 100ml solution and contains 10-30g in the pharmaceutical composition of the present invention.Though known vitamin B
12Or derivatives thereof has bactericidal action, but involve than the deep subcutaneous tissue and have latent infection particularly bacillus pyocyaneus, escherichia coli and infection of staphylococcus aureus etc. for damage, the gentamycin that for this reason, also can add relative a small amount of in the compositions of the present invention.The content of gentamycin in pharmaceutical composition of the present invention is generally every 10ml solution (in the 10g ointment) and contains 8 kilounits.
Pharmaceutical composition of the present invention also can contain and some otherly has collaborative or assosting effect but not antagonism natural, synthetic or chemical compound that reorganization produces mutually except that containing above-mentioned effective ingredient.Such chemical compound comprises but is not only limited to immunostimulant or regulators such as cell growth factor such as other antibiotic, epidermal growth factor and fibroblast growth factor, interleukin and interferon except that gentamycin, and other keratinocyte lytic agents, UV absorbers etc.
Can be according to the known method in pharmaceuticals industry field (for example referring to Remington ' s PharmaceuticalSciences, Mack Pub.Co., Easton, Pa., 1980) pharmaceutical composition of the present invention is made solution, spray, cream, Emulsion, ointment or the gel that is suitable for topical or passes through skin or mucosa absorption administration.
Under the situation of preparation solution, sterile distilled water, water for injection, isotonic sodium chloride or glucose solution be can use, and the solvent of ethanol or polyhydric alcohol (as ethylene glycol, propylene glycol and liquid polyethylene glycol etc.) or disperse medium contained as carrier or diluent.Under any circumstance, said preparation all should be aseptic and flowable.In addition, under production, transportation and condition of storage, said preparation also must be stable, and can be to contamination by micro such as antibacterium and funguses.In case of necessity, also can add antioxidant (as anti-bad hydrochloric acid), antibiotic (as antifungal) and antiseptic (as sodium benzoate, chlorobutanol, degree rice phenol, sorbic acid etc.).
In order to prepare the non-current preparation that is suitable for external or topical, can be at first with vitamin B
12The gentamycin powder dissolution of Jia Ruing is in water-bearing media or other appropriate carriers or substrate in case of necessity, then with resulting solution and suitable substrate or excipient uniform mixing, to make Emulsion, cream, ointment or the gel that is suitable for the part or passes through skin or mucosa absorption administration.Can be used for preparing the substrate of these preparations or excipient and comprise but be not only limited to glycerol, magnesium stearate, Polyethylene Glycol, polyacrylamide, cholesterol, lecithin, methylcellulose or carboxymethyl cellulose, Pulvis Talci, lactose, glucosan, starch, glyceride, acrylate, paraffin, methyl butex, lanoline, vaseline, methyl hydroxybenzoate and ethyl ester, and tween and span etc.
In case of necessity, also can be with the vitamin B of pre-preparation
12Solution and suitable cutaneous permeable agent such as dimethyl sulfoxide or laurocapram mix, pharmaceutical composition of the present invention is made spray or aerosol.
Pharmaceutical composition of the present invention can be used for prevention and radiation skin injury such as radiotherapy dermatitis, II-III degree radiation burn and radioactivity pigmentation, and other on-radiation skin injury and pathological changes.Said other on-radiation skin injurys and pathological changes comprise but are not only limited to common burn, solar dermatitis, specificity eczema, tinea manus and pedis and tinea cruris, seborrheic dermatitis, and the chapped skin relevant with dysbolismus and skin aging, pruritus and shallow table ulcer etc.
Though the relevant reason of cutter really still imperfectly understands at present, our laboratory observation is tentative confirmation, and is of the present invention with vitamin B
12For the pharmaceutical composition of primary activity composition to the therapeutical effect of above-mentioned various radioactivity and on-radiation skin injury may with vitamin B
12Participate in the nucleic acid metabolism of cell, the RNA that increases cell is synthetic, promotes vascular endothelial cell, Interstitial cell and the myocyte's of damaged skin renewal, and then it is relevant with tissue repairing ability to improve the local microcirculation of skin histology.
As the unique a kind of cobaltic vitamin of trace element, vitamin B of containing
12Cobalt atom in the molecule combines with porphyrin ring by coordinate bond.Yet this combination is unstable, makes it to be easy to be removed or to be replaced by other groups.Therefore, vitamin B
12Enter and to be dissociated into cobalt atom and two parts of porphyrin in the body, and these two parts can be brought into play synergism in vivo.
Vitamin V B
12As the essential coenzyme of multiple metabolic process, participate in the synthetic of nucleus (as DNA, RNA) and nucleoprotein.Therefore, vitamin V B
12Have the sulfhydryl oxidase of preventing, keep the normal metabolic function of cell.
Radioactive radiation acts on water generates oxygen and hydroxyl free radical (peroxide), and especially the Degradation of these radical pairs DNA (DNA (deoxyribonucleic acid)) and RNA (ribonucleic acid) may be the fundamental cause that causes radiation injury.VB
12In cobalt element have reduction, can make free radical again in conjunction with (becoming water again), thereby the activity that has reduced free radical has also reduced its infringement to human body.
On the other hand, because cyanocobalamin contains cyano group, cyanogen can increase zmount of oxygen consumption or be easy to and combines with oxygen, makes local organization form hypoxia, thus but " radioprotective " ability of enhancing body.
We confirm vitamin B by Intraventricular, whole body and the local application experiment to animal
12Has the dual analgesic activity of maincenter and periphery, 1/4 of the similar quite morphine of action intensity, and this effect and its reduction pain threshold relevant (data not shown goes out) in quick district bitterly.
Use amount to pharmaceutical composition of the present invention does not have strict restriction, but generally pharmaceutical solutions applies 1-10 time every day, but other nonfluid preparations apply 1-6 time every day.Yet definite medication number of times and dosage will be according to the size and the orders of severity of damage, whether have concurrent infection, and patient factor such as the sensitivity of medicine is decided.
The following example is intended to further illustrate, rather than restriction the present invention.Under the prerequisite of the present invention spirit and principle, any change that the indivedual inessential technical characterictic of the present invention is done and change all will fall into the present invention and await the reply in the scope of claim.EXAMPLE Example 1: the preparation of the ointment formulation of pharmaceutical composition of the present invention
Present embodiment is lifted the preparation method of the ointment formulation of describing pharmaceutical composition of the present invention.
In order to prepare the ointment formulation of pharmaceutical composition of the present invention, at first with the 50.0g vitamin B
12(the honest and clean company limited of north, North China pharmacy group China) is dissolved in about 30ml distilled water, simultaneously 1.6 ten thousand unit gentamycin sulfate is dissolved in 20ml and is heated in about 60 ℃ distilled water, obtains solution I and II respectively.
Take by weighing 25g lanoline, 5g vaseline, 20g γ-Radix Oenotherae erythrosepalae oil, 0.1g vitamin E, 30ml10% methyl hydroxybenzoate, 15g Tween 80 and 5g sorbester p17 then respectively and add in the rustless steel container successively, again to wherein adding the about 20ml of distilled water, obtain solution III after simple mixing and heating (the about 60 ℃) fusing.Solution I, II and the III that abundant then mixing as above obtains also continues stir about 10 minutes, obtains the ointment formulation of about 100g pharmaceutical composition of the present invention.
Compound vitamin B
12Ointment prepares foundation:
Each component is to the influence of radiation-induced skin ulcer healing (group number of animals (only) healing time of X ± SD) (my god) healing rate (mm in table 1 substrate
2/ day) lanoline 7 28.6 ± 2.64 14.6 ± 2.09
*R-Radix Oenotherae erythrosepalae oil 7 27.3 ± 2.06 13.0 ± 1.45
*Vaseline 7 29.7 ± 3.15 10.2 ± 1.82 models contrast 7 34.7 ± 2.75 6.9 ± 1.92 with the vaseline group relatively:
*P＜0.01
From last tabulation 1 as seen, lanoline, γ-Radix Oenotherae erythrosepalae oil and vaseline do not have obvious influence to healing time, also there was no significant difference between the three; With regard to healing rate, though three and model group relatively all can be accelerated healing rate, lanoline, γ-Radix Oenotherae erythrosepalae oil and vaseline compare, and effect is more obvious, and group difference is remarkable, P＜0.01.Therefore determine lanoline, γ-Radix Oenotherae erythrosepalae oil main matrix as pharmaceutical composition of the present invention (ointment).Because chronic radioactive skin ulcer and fibrosis on every side, so preparation is preferably gala shape ointment, with the reinforcement drain and make medicine in the local action time lengthening.Because of vitamin B
12Easily oxidized, the liquid oil preparation vitamin E of adding 0.1% can increase by half flowability of preparation, and play antioxidation, strengthens stability of formulation.Embodiment 2: pharmaceutical composition of the present invention (ointment) is to the preventive effect of radiation skin injury
Present embodiment is intended to observe the preventive effect of pharmaceutical composition of the present invention (ointment) to animal pattern (Cavia porcellus) radiation skin injury.
The healthy guinea pig of 40 average weight 250-300g is divided into four groups at random, and 10 every group: (1) only waits the model group of dosage normal saline; (2) wait dosage not contain vitamin B
12The negative control group of ointment base; (3) wait the positive controls of dosage control drug; (4) give the experimental therapy group of pharmaceutical composition of the present invention (ointment).
After the grouping, under the same conditions with local (2.5 * 2.5cm on the left of the back of all animals of x-ray bombardment
2) skin, to cause II degree acute radiation skin injury model.Employed illuminate condition is: per minute 0.9 gray(Gy), accumulated dose 60 gray(Gy)s.Irradiation and between twice irradiation two days at interval at twice.Irradiation voltage is 100 kilovolts, and electric current is 10 millivolts.Radiation source is 30cm apart from the distance of skin surface, and the centre does not have filter plate.
From the irradiation beginning promptly to the local skin coating said medicine or the contrast agents of each treated animal.Wherein the employed control drug of positive controls is the burn treating medicine of commodity " SHAOTANGNING OINTMENT " (production of Tianjin Jin Dong pharmaceutical factory) by name.1 about 0.5g-1g of local coating every day; Continuous use 15 days.During the treatment, situation appears in the skin injury of observing and write down animal every day.Shown in the following tabulation 1 of result. table 2 pharmaceutical composition of the present invention (ointment) is penetrated the 1st day 16.4 ± 1.17 obvious negative control group 10 1.0 to the impact of Changes of Radiation Damaged Skin time of occurrence (group number of animals topical dose (g) the beginning administration time skin of X ± SD) decrease time of occurrence (day) the restless behavior model group 10 1.0 of animal and is penetrated appearance notes of 17.0 ± 1.56 accidental positive controls 10 1.0 irradiations in the 1st day, 22.2 ± 1.75 accidental treatment groups 10 1.0 irradiations in the 1st day the 1st day 28.2 ± 1.48: the ratio for the treatment of group and model group: P＜0.05 ... P＜0.01
From the result shown in the table 2 as can be seen, the model group animal on average skin injury occurs in about 15-17.5 days after x-ray bombardment.Simultaneously visible animal restlessness, and every now and then with its exposure position skin friction even collision cage wall.These performances of inferring animal may be because due to the impaired local skin pruritus.Equally, acceptance waits dosage not contain vitamin B
12The negative control treated animal of ointment base skin injury appears about 15.5-18.5 days after x-ray bombardment begins on average, and at whole viewing duration behavior performance similar in appearance to the model group animal appears.On the contrary, acceptance waits then average after x-ray bombardment begins about 20.5-24 days of the positive control treated animal of dosage control drug skin injury to occur, and the restless obvious minimizing of animal.And the time of local skin damage appears in the treatment treated animal of accepting pharmaceutical composition of the present invention (ointment) even extend to x-ray bombardment after beginning about 26.8-29.6 days, and animal does not almost completely have restlessness and with the behavior of exposure position skin friction cage wall.
Above-mentioned these results show that pharmaceutical composition of the present invention can delay the time of occurrence that heavy dose of x-ray bombardment causes skin injury effectively, and can alleviate the order of severity of radiation injury effectively.As if in addition, experimental result also shows, compares with known burn treating medicine, and pharmaceutical composition of the present invention decreases (burning) wound to radioactivity and has better preventive effect.Embodiment 3: pharmaceutical composition of the present invention (ointment) is to the therapeutical effect of radiation skin injury
Present embodiment is intended to observe the therapeutical effect of pharmaceutical composition of the present invention (ointment) to animal pattern (Cavia porcellus) skin reflex damage.
Basically carry out animal grouping; Preparation animal model; Administration and observation according to the method described in the embodiment 2.Different is; Promptly animal is carried out the skin injury topical the same day of causing II degree acute radiation skin injury, (the group number of animals of X ± SD) is coated with pharmaceutical quantities (g) beginning administration time skin and decreases 10 1.0 damages of curative day model group and 16.4 ± 1.17 negative control group, 10 1.0 damages on the same day occur and 17.0 ± 1.56 positive controls, 10 1.0 damages on the same day occur and 22.2 ± 1.75 treatment groups, 10 1.0 damages on the same day occur and the same day 28.2 ± 1.48 occurs and every day 1 time is till the damage recovery from illness.Shown in the following tabulation 3 of result. table 3 pharmaceutical compositions of the present invention (ointment) to the treatment effect of Changes of Radiation Damaged Skin
From the result shown in the table 3 as can be seen, the on average recovery from illness of about 27.3-26.6 days after x-ray bombardment of the skin injury of model group animal.Equally, acceptance waits dosage not contain vitamin B
12On average about 24.7-29.3 days after the x-ray bombardment recovery from illness of skin injury of negative control treated animal of ointment base.On the contrary, acceptance waits the then average recoveries from illness in about 23.4-26.6 days after x-ray bombardment of skin injury of the positive control treated animal of dosage control drug.And accept pharmaceutical composition of the present invention (ointment) experimental therapy treated animal local skin damage healing time in addition foreshorten to x-ray bombardment after about 14-11.5 days.
Above-mentioned these results show that pharmaceutical composition of the present invention can be treated heavy dose of x-ray bombardment effectively and be caused skin injury.And, to compare with known burn treating medicine, pharmaceutical composition of the present invention decreases the performance of (burning) wound to radioactivity better therapeutic effect.Embodiment 4: pharmaceutical composition of the present invention (cream) burns the therapeutical effect that (scalding) hinders to on-radiation
Present embodiment uses the Cavia porcellus animal model to observe the therapeutical effect of pharmaceutical composition of the present invention to the on-radiation skin burn.
30 of the Cavia porcelluss of average weight 540g are divided into 3 groups at random, 10 every group: model group, negative control group, positive controls and treatment group.Each treated animal lumbar injection 2% pentobarbital sodium (p-Na) (30mg/kg) anaesthetize after, use the 75w electric cautery, the back after shaving hair causes local skin II ° of the about 2 * 2cm of size to burn (scalding) wound.
After damage causes, immediately in damage local coating therapeutic agent or control formulation: the treatment treated animal applies that pharmaceutical composition of the present invention (ointment), the commercially available burning (scalding) of positive control treated animal coating are hindered medicine SHAOTANGNING emulsifiable paste (production of Tianjin Jin Dong pharmaceutical factory), the negative control treated animal applies and do not contain vitamin B
12Ointment base; Model group animal do not apply any therapeutic agent or contrast agents.Behind the coating, (the group number of animals of X ± SD) is red and swollen and ooze out scabies secondary infection damage curative day model group 10 10,/10 8,/10 19 negative control group 10 8,/10 9,/10 17 positive controls 10 8,/10 5,/10 15 treatment groups 10 5,/10 4,/10 12 to the treatment effect of on-radiation skin scald for cover and bind up a wound with antiseptic gauze.Change dressings every day once and observe wound repair and healing state every day.Shown in the following tabulation 4 of result. table 4 pharmaceutical compositions of the present invention (ointment)
From the result shown in the table 4 as can be seen, the on average recovery from illness of about 19 days after scalding of the skin injury of model group animal.Equally, acceptance waits dosage not contain vitamin B
12The on average recovery from illness of about 17 days after scalding of skin injury of negative control treated animal of ointment base.On the contrary, acceptance waits the then on average recovery from illness of 15 days after scalding of skin injury of the positive control treated animal of dosage control drug.And accept pharmaceutical composition of the present invention (ointment) experimental therapy treated animal local skin damage healing time in addition foreshorten to scald after about the 12nd day.
In addition, use pharmaceutical composition of the present invention after, animal local damage performance (red and swollen and ooze out, and secondary infection) also obviously alleviates.Therefore, these results show that pharmaceutical composition of the present invention can alleviate the symptom that the animal local skin is scalded effectively, quicken the healing of damage, and have fabulous analgesic effect, and overall therapeutic effect obviously is better than known burn treating medicine SHAOTANGNING emulsifiable paste.Embodiment 5: pharmaceutical composition of the present invention (ointment) is to the therapeutic effect of on-radiation skin injury or pathological changes
Present embodiment is intended to illustrate the clinical therapeutic efficacy of pharmaceutical composition of the present invention to damage of various skin on-radiation or pathological changes.(1) pharmaceutical composition of the present invention (ointment) scalds the therapeutical effect that (burning) hinders to II degree on-radiation
Clinical observation pharmaceutical composition of the present invention therapeutic effect that 110 examples (age 5-86 year) II degree on-radiation is scalded (burning) sick and wounded people.Other has the similar patient of the 100 routine state of an illness then to use commercially available SHAOTANGNING emulsifiable paste (50 example) or antimicrobial ointment (50 example) in contrast.Only clean the skin ulcer face, adopt four layers of gauze to be coated with ointment outward, change dressings every day 2 times with normal saline.Shown in the following tabulation 5 of result.
Table 5 pharmaceutical composition of the present invention (ointment) treatment II degree on-radiation scalds (burning) sick and wounded people's the invalid effective percentage VB of observation of curative effect group example number healing improvement
12Compositions 110 96 14 0 100% SHAOTANGNING emulsifiable pastes 50 24 20 6 88% antimicrobial ointments 50 18 20 12 76.0% (2) pharmaceutical compositions of the present invention (ointment) are to the therapeutical effect of eczema
Clinical observation the therapeutic effect of pharmaceutical composition of the present invention to 103 examples (age 1-48 year) eczema patient.Wherein use treatment group patient 69 examples of pharmaceutical preparation of the present invention (ointment); Use matched group patient 34 examples of control drug 3% boric acid solution.Damage location coating pharmaceutical composition ointment formulation of the present invention.Patient keeps free movement of the bowels during the treatment, does not eat maror.Shown in the following tabulation 6 of observed result.
Table 6 pharmaceutical composition of the present invention (ointment) treatment eczema patient's observation of curative effect group example number is cured the invalid effective percentage VB that takes a turn for the better
12Compositions 69 48 13 8 88.4%3% boric acid solution 34 16 11 7 79.4% (3) pharmaceutical compositions of the present invention (cream) are to the therapeutical effect of solar dermatitis
Clinical observation the therapeutic effect of pharmaceutical composition of the present invention to 84 examples (age 15-46 year) solar dermatitis patient.Wherein use treatment group patient 52 examples of pharmaceutical preparation of the present invention (cream); Use matched group patient 32 examples of control drug calamine lotion.Shown in the following tabulation 7 of observed result.Table 7 pharmaceutical composition of the present invention (cream) treatment solar dermatitis patient's observation of curative effect group example number recovery from illness improvement invalid effective rates group: B
12Compositions 52 50 20 100% matched groups: calamine lotion 32 8 13 11 65.6% (4) pharmaceutical compositions of the present invention (Emulsion) are to the therapeutical effect of tinea pedis
Clinical observation the therapeutic effect of pharmaceutical composition of the present invention to 81 examples (age 24-78 year) tinea pedis patient.Wherein use treatment group patient 45 examples of pharmaceutical preparation of the present invention (Emulsion); Use matched group patient 36 examples of control drug new ointment for tinea pedis.Partial smearing 2 times/day.Shown in the following tabulation 8 of observed result.Table 8 pharmaceutical composition of the present invention (Emulsion) treatment tinea pedis patient's the invalid effective percentage VB of observation of curative effect group example number recovery from illness improvement
12Compositions 45 40 50 100% new ointment for tinea pedis 36 21 96 83.3% (5) pharmaceutical compositions of the present invention (cream) are to the therapeutical effect of seborrheic dermatitis
Clinical observation the therapeutic effect of pharmaceutical composition of the present invention to 63 examples (age 18-32 year) seborrheic dermatitis patient.Wherein use treatment group patient 41 examples of pharmaceutical preparation of the present invention (cream); Use matched group patient 22 examples of the strong peroxide deionized water of contrast medicament.Partial smearing 2 times/day also avoids using oxidant sterilization wound surface.During treating, keep free movement of the bowels, do not eat maror.Shown in the following tabulation 9 of observed result.Table 9 pharmaceutical composition of the present invention (cream) treatment seborrheic dermatitis patient's the invalid effective percentage VB of observation of curative effect group example number recovery from illness improvement
12Compositions 41 22 11 8 the last 80.5% peroxide deionized waters 22 10 57 68.1% (6) pharmaceutical compositions of the present invention (ointment) are to the therapeutical effect of contact dermatitis
Clinical observation the therapeutic effect of pharmaceutical composition of the present invention to 48 examples (age 11-44 year) contact dermatitis patient.Wherein use treatment group patient 28 examples of pharmaceutical preparation of the present invention (ointment); Use matched group patient 20 examples of control drug calamine lotion.Partial smearing 2 times/day also avoids using oxidant sterilization wound surface.During treating, do not use various soap to wash one's face or have a bath as far as possible.Shown in the following tabulation 10 of observed result.Table 10 pharmaceutical composition of the present invention (ointment) treatment contact dermatitis patient's the invalid effective percentage VB of observation of curative effect group example number recovery from illness improvement
12Compositions 28 21 43 89.2% calamine lotions 20 10 46 70.0% (7) pharmaceutical compositions of the present invention (Emulsion) are to the therapeutical effect of contact dermatitis
Clinical observation pharmaceutical composition of the present invention to chap patient's therapeutic effect of 39 examples (age 51-82 year) vola.Wherein use treatment group patient 24 examples of pharmaceutical preparation of the present invention (Emulsion); Use matched group patient 15 examples of control drug urea frost.Partial smearing 2 times/day.Shown in the following tabulation 11 of observed result.Patient's the observation of curative effect group example number recovery from illness invalid effective percentage VB that takes a turn for the better chaps in table 11 pharmaceutical composition of the present invention (Emulsion) treatment vola
12Compositions 24 20 40 100% urea frost 15 843 80.0%
Above clinical treatment observation result (referring to table 5-11) convincingly demonstrates, and is of the present invention with vitamin B
12Can treat effectively for the externally-applied medicinal composition of primary activity composition and to comprise common burn, solar dermatitis, specificity eczema, tinea manus and pedis and tinea cruris, seborrheic dermatitis, and the xerosis cutis relevant with dysbolismus and skin aging, chap and pruritus in interior multiple on-radiation skin injury or pathological changes.
Claims (9)
1, a kind of pharmaceutical composition that is used to prevent and treat the local skin pathological changes is characterised in that said pharmaceutical composition is by vitamin B basically
12Or derivatives thereof and one or more pharmaceutically acceptable carriers or excipient are formed.
2, according to the pharmaceutical composition of claim 1, wherein said pharmaceutical composition also can contain Radix Oenotherae erythrosepalae oil.
3, according to the pharmaceutical composition of claim 1, wherein said pharmaceutical composition also can contain gentamycin.
4, according to the pharmaceutical composition of claim 1, wherein said pharmaceutical composition also can contain one or more and have collaborative or assosting effect but other active component of antagonism not mutually.
5, pharmaceutical composition according to claim 1, wherein said local skin pathological changes is selected from radiodermatitis, radiation burn, radioactivity pigmentation, common burn, solar dermatitis, specificity eczema, diaper rash, tinea manus and pedis and tinea cruris, seborrheic dermatitis, and the xerosis cutis relevant with dysbolismus and skin aging, chap, pruritus and shallow table ulcer.
6, according to the pharmaceutical composition of claim 1, wherein said pharmaceutical composition is a local topical administration.
7, according to the pharmaceutical composition of claim 1, wherein the dosage form of said pharmaceutical composition is selected from ointment, solution, Emulsion, paste and gel.
8, vitamin B
12Be used for preventing application with the medicine of radiotherapy and damage of on-radiation local skin or pathological changes in production.
9, application according to Claim 8, damage of wherein said local skin and pathological changes are selected from radiodermatitis, radiation burn, radioactivity pigmentation, common burn, solar dermatitis, specificity eczema, diaper rash, tinea manus and pedis and tinea cruris, seborrheic dermatitis, and the xerosis cutis relevant with dysbolismus and skin aging, chap, pruritus and shallow table ulcer.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03127032 CN1201747C (en) | 2003-05-19 | 2003-05-19 | External applied medicine composition containing vitamin B |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03127032 CN1201747C (en) | 2003-05-19 | 2003-05-19 | External applied medicine composition containing vitamin B |
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| Publication Number | Publication Date |
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| CN1456170A true CN1456170A (en) | 2003-11-19 |
| CN1201747C CN1201747C (en) | 2005-05-18 |
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| CN 03127032 Expired - Lifetime CN1201747C (en) | 2003-05-19 | 2003-05-19 | External applied medicine composition containing vitamin B |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100400049C (en) * | 2006-05-09 | 2008-07-09 | 岳邦珅 | Medicinal powder for treating beriberi and preparation method thereof |
| CN101669888B (en) * | 2009-09-27 | 2010-12-29 | 纪辉 | New application of vitamin B12 in cosmetics |
| CN105213416A (en) * | 2015-11-04 | 2016-01-06 | 杨小玉 | A kind of pharmaceutical composition for the treatment of mucocutaneous injury |
| CN106039315A (en) * | 2016-08-11 | 2016-10-26 | 于凌波 | Pregnant vulva eczema nursing drug and preparation method thereof |
| CN106177693A (en) * | 2016-09-27 | 2016-12-07 | 泰山医学院 | A kind of Chinese medicine for treating eczema and compound recipe solution thereof |
| CN107737131A (en) * | 2017-12-12 | 2018-02-27 | 杨小玉 | A kind of skin and mucosa damages antibacterial disinfectant and preparation method |
-
2003
- 2003-05-19 CN CN 03127032 patent/CN1201747C/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100400049C (en) * | 2006-05-09 | 2008-07-09 | 岳邦珅 | Medicinal powder for treating beriberi and preparation method thereof |
| CN101669888B (en) * | 2009-09-27 | 2010-12-29 | 纪辉 | New application of vitamin B12 in cosmetics |
| CN105213416A (en) * | 2015-11-04 | 2016-01-06 | 杨小玉 | A kind of pharmaceutical composition for the treatment of mucocutaneous injury |
| CN106039315A (en) * | 2016-08-11 | 2016-10-26 | 于凌波 | Pregnant vulva eczema nursing drug and preparation method thereof |
| CN106177693A (en) * | 2016-09-27 | 2016-12-07 | 泰山医学院 | A kind of Chinese medicine for treating eczema and compound recipe solution thereof |
| CN107737131A (en) * | 2017-12-12 | 2018-02-27 | 杨小玉 | A kind of skin and mucosa damages antibacterial disinfectant and preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1201747C (en) | 2005-05-18 |
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