CN105770896A - Application of photodynamic combination of composition containing photosensitive molecules to acne treatment medicament - Google Patents
Application of photodynamic combination of composition containing photosensitive molecules to acne treatment medicament Download PDFInfo
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- CN105770896A CN105770896A CN201610297225.7A CN201610297225A CN105770896A CN 105770896 A CN105770896 A CN 105770896A CN 201610297225 A CN201610297225 A CN 201610297225A CN 105770896 A CN105770896 A CN 105770896A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
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Abstract
The invention relates to an application of a photodynamic combination of a composition containing photosensitive molecules to an acne treatment medicament. The photodynamic combination comprises the composition containing the photosensitive molecules (1) and a light source (2). The light source in the combination provides energy for exciting the photosensitive molecules, and photosensitizer molecules excited by photons carrying specific energy; the photosensitizer molecules can transfer energy to oxygen molecules in an organism to form oxygen in a high-energy state; the high-energy oxygen molecules kill propionibacterium acnes and staphylococcus aureus as adjacent target germs. By adopting the photodynamic combination of the composition containing the photosensitive molecules, fungal infection occurring in an acne treatment process is avoided effectively. Through application of the combination to preparation of the acne treatment medicament, the composition of the photosensitive molecules is effectively combined with the light source to form the photodynamic combination, and a novel application of the photodynamic combination of the composition containing the photosensitive molecules to the field of acne treatment medicaments is developed.
Description
Technical field
The invention provides the light power combination of the compositions of a kind of photosensitive molecular, relate generally to the application in abundance type acne treatment drug of the light power combination of compositions of photosensitive molecular.
Background technology
Existing acne treatment method, mainly includes chemical medicinal treatment, Chinese herbal medicine anti-acne therapy and photodynamic therapy.
Wherein chemical medicinal treatment includes following several:
One, glucocorticoid method: glucocorticoid itself can bring out acne, life-time service will make immunity of organisms reduce, and cause other side effect.
Two, antibiotic method: antibiotic can antibacterial anti-acne, but reuse antibiotic and may result in drug resistance and skin injury.And the drug resistance of pathogenic bacterium will make associated antibiotic lose curative effect.
Three, salicylic acid (fruit acid) method: the excessive concentration of salicylic acid (fruit acid), pH value are little, use overlong time, all can cause damage and other side effect of skin.Salicylic acid (fruit acid) the product needed physician guidance of high concentration uses.
Four, the cycle of the physical therapy of Chinese herbal medicine anti-acne therapy is long, takes effect slow.
Antibacterial is the key of anti-acne, is badly in need of the antibacterial anti-acne method of the highly effective and safe of a kind of non-antibiotic.
Over nearly 10 years, photodynamic therapy (PhotodynamicTherapy, PDT) is the method for emerging a kind of antibacterial therapy acne, energy high-efficiency antimicrobial anti-acne, and does not produce drug resistance.Along with the development of the research of photosensitive molecular, the requirement having related parameter of photosensitizer is also differed by different fields, and different clinical applications requires that different photosensitizer matches.Desirable novel photosensitive agent needs to meet following requirement: 1. component is single, and structure is clear and definite；2. convenient administration, shortens the time being administered into treatment；3. excretion is fast, toxicity, side effect is little, and the lucifuge time is short；4. there is higher functioning efficiency, produce the oxygen (ROS) of enough upper state；5. absorbed by selectivity on pathological tissues, health tissues should not be absorbed or few absorption；6. there is the effect wavelength of coupling with corresponding treatment disease, etc..
CN201380020826 patent disclosure a kind of bio-photon compositions, test kit and method, adopt the compositions of photosensitive molecular of several chromophore for photon delicate skin, this compositions comprises three class chromophores, solves the general toxicity directly contacted due to photosensitizer and tissue or localized toxic.The weak picked-up of photosensitizer is in target tissue, and this type of existing scheme generally confirms low therapeutic efficiency.
CN200880117950 discloses a kind of compositions for photodynamic skin treatment, this combination includes CHLOROPHYLLINE and aminolevulinic acid, 5-ALA (the aminolevulinicacid that compositions adopts, ALA) and derivant itself be not photosensitive molecular, but can synthesize the photosensitive molecular of macro ring for human skin, in use procedure, consumption is relatively larger.Skin is had very strong side effect by this quasi-molecule of 5-ALA simultaneously, and red swelling of the skin often occurs in patient, bubbles, also needs to lucifuge a few hours after treatment.For this, the method can only control to use under department of dermatologry medical practitioner instructs.
During many anti-acnes treatment simultaneously, many people catch the acne in contacting surface portion carelessly, it is easy to cause fungal infection and superinfection so that treatment of smallpox process occurs repeatedly.
At present, it is badly in need of developing a kind of uncomplicated smooth dynamical system of composition that can be applicable to photodynamic therapy acne, simultaneously skin side-effects is little, without lucifuge, photosensitive molecular light trans-utilization rate is high simultaneously, be conducive to efficiently treating acne, in treatment acne process, reduce fungal infection and the superinfection of acne simultaneously.
Summary of the invention
It is an object of the present invention to provide the light power combination of the compositions of a kind of photosensitive molecular, by suitable light power combination, it is achieved photosensitive molecular acne-removing, it is to avoid the phototoxicity of photosensitive molecular, effectively prevent fungal infection and superinfection simultaneously.
It is a still further object of the present invention to provide the application in abundance type acne treatment drug of the light power combination of the compositions of a kind of photosensitive molecular, it is by utilizing photodynamic therapy technology effectively to suppress propionibacterium acnes, Candida albicans and staphylococcus aureus, effectively prevent fungal infection in therapeutic process, be finally reached the purpose of anti-acne.
Two principal characters according to the present invention, described light power combination comprises the compositions of (1) photosensitive molecular；(2) red-light source；
Described photosensitive molecular for tartrazines, curcumin, riboflavin 5'-monophosphate sodium salt, lure red AC, new coccine, Chromotrope FB, indigo carmine, erioglaucine disodium salt, fast green FCF, Lissamine green B, naphthol green or acid green, alkermes, Xylene Red azorubine, amaranth, brilliant scarlet G 4R, brilliant black BN (PN), the brown HT of chocolate, beta-carotene, bixin, lycopene, betanin, riboflavin, the red B sodium salt of algae and mixture thereof；Preferred indigo carmine, erioglaucine disodium salt, fast green FCF, Lissamine green B.
Light source can use any suitable light.Such as, low power sources or diode laser light source can be used.Any suitable light can be used, for instance visible or iraser.Also high-energy black light can be used, for instance tungsten halogen or xenon arc light source.Also LED light source can be used.The advantage using LED light source is that it will reduce the probability producing uncomfortable heat, therefore causes the discomfort reducing experimenter.Whole involved area can be implemented illumination procedure.Especially preferably face, the whole internal implementation of back are irradiated.Such as, can be operable to light source irradiate accessible inner surface.Or, only irradiate some regions.Such as, can indivedual acnes of irradiation area.Light source may be suitable for all regions of face, including underthe nose, forehead, face cheek and surface thereof everywhere.
Can using any device of the light being suitable to launch wavelength described above, energy dose and luminous power, including pocket lamp, chargeable flashlight or desk lamp device, alternative light source includes the most luminotherapeutic device that can irradiate acne spots at once.
Further saying, light source each action time is 0.5-30 minute, it is preferable that 2-10 minute, it is ensured that photosensitive molecular irradiation time.
Described red-light source can be applied on skin, and expection utilizes wavelength between 400nm and 700nm, it is preferable that between 400-500nm and 600-700nm, causes the activation of described photosensitive molecular (photosensitive molecular).The light source using this wavelength makes it possible to the (infiltration of about 5-8mm rank under the gratifying infiltration of described photosensitive molecular, the i.e. level of corium) work, photosensitization molecule is subject to the light source irradiation of specific wavelength simultaneously, produce upper state oxygen, killing propionibacterium acnes and staphylococcus aureus, photosensitive molecular and additive synergism effectively suppress Candida albicans simultaneously.
Further saying, the composition of the additive in the compositions of photosensitive molecular is the one in piroctone olamine salt, Zinc Pyrithione, climbazole, allantoin；Preferred piroctone olamine salt and the one in allantoin.
Further saying, the compositions of photosensitive molecular is with the weight percent meter of compositions, and photosensitive molecular is 0.0001%-50%, and additive is 0.001%-1%, and all the other are water phosphate buffer.
Further saying, the weight percent meter of the compositions of photosensitive molecular, photosensitive molecular 0.001%-10%, additive is 0.015%-0.5%, and all the other are water phosphate buffer.
Further saying, in the compositions of photosensitive molecular, photosensitive molecular is 50000:1-1:10000 with the ratio of additive；Preferred 2000:3-1:5000.
The light power combination of the present invention, the additive in the compositions of described photosensitive molecular adds the viscosity of the system that is effectively improved, it is simple to smearing in acne treatment process.
The light power combination of the present invention, the compositions of described photosensitive molecular uses with liquid, semisolid, solid or aerosol form.The forms such as such as water solublity or insoluble muddy suspension, solution, curry, Emulsion (including cream), ointment, gel, serosity, suppository, tablet, capsule or fine spray agent are used.
The light power combination of the compositions of photosensitive molecular of the present invention is mainly used in the treatment of propionibacterium, the particularly treatment of propionibacterium acnes, including that occurred and potential.According to character, the order of severity and/or position, acne can be categorized into multi-form, for instance blackhead, Whiteheads, pimple, pustule and/or cyst.Include homeliness type acne, acne erythematosa, spherical acne, acne papulosa and the acne before menstrual period according to the medicable representative acne type of the present invention, effectively prevent the fungal infection in therapeutic process simultaneously.The present invention is preferentially used for acne vulgaris, and acne may alternatively appear in back, chest, upper arm and/or face；Therapeutic Method provided by the invention can be used for treating any of above body position, particularly face.
The beneficial effects of the present invention is:
1, the compositions of photosensitive molecular and light are combined and are used for acne treatment by the present invention, and its therapeutic effect is good, and without antibiotic, without hormone, do not produce that drug resistance, side effect be little, safety non-toxic and economical and practical, the photosensitive molecular structure of employing is single, and safety is high.
2, the present invention efficiently can quickly kill propionibacterium and the staphylococcus aureus that induction acne occurs, green pus bacterium, treats acne, but do not damage normal cell, effectively prevent fungal infection in conjunction with additive, reduce the risk of superinfection, suppress the folliculitis that chlosma causes further.
3, active drug consumption of the present invention is little, and the effect killing acne pathogenic bacterium is strong.
4. the present invention takes photosensitive molecular as anti-acne system, and the light source in conjunction with different-waveband uses, and can effectively strengthen system bactericidal effect, hence it is evident that reduce anti-acne course for the treatment of.
5. the photosensitive molecular of the present invention adopts food additive or light-sensitive coloring agent, and safety is high, simultaneously good water solubility, high with the compatibility of additive compound, does not have degradation phenomenon under precipitation, antibacterial efficiency.
Detailed description of the invention
Photosensitive molecular is alternatively water solublity and is scattered in the pearl in whole face or topical acne medicine, bar or small container.The wavelength to the light used and optics dosage can be used and to the stable ingredient of photosensitizer.Other compositions are not preferably by the wavelength absorption of light.It addition, germ killing drugs can contain more than one photosensitive molecular to give different consumers acceptable color.For the photosensitive molecular absorbing wavelength of common low toxicity of the present invention in Table 1.
Table 1 photosensitive molecular maximum absorption wavelength
Following example illustrate the present invention, but are not limiting as its scope.In these embodiments, unless otherwise noted, number and percentage ratio are based on weight and provide, the photosensitive molecular that photosensitive molecular is mentioned in claim, additive illustrates for piroctone olamine salt, this embodiment is only used as understanding, is not limited in claim photosensitive molecular and additive combination.
The embodiment of the table 2 light power combination containing photosensitive molecular
Embodiment 1
Weigh up each constituent content according to table 2,0.0001% photosensitive molecular solution is mixed with 0.0001% piroctone olamine salt and moisture, after fully dissolving, supply excess water, regulate pH to 5, at 0.1J/cm2Under light intensity, under 400nm wavelength, anaerobic species, the antibacterial efficiency of fungus being reached 99%, matched group variable light source adopts nature light, and other conditions are constant, and experimental group is apparently higher than the antibacterial efficiency of matched group (see table 2).
Embodiment 2
Weigh up each constituent content according to table 2 to be mixed with 0.5% piroctone olamine salt and moisture by 0.0001% photosensitive molecular solution, after fully dissolving, supply excess water, regulate pH to 7, at 100J/cm2Under light intensity, under 600nm wavelength, anaerobic species, the antibacterial efficiency of fungus being reached 99%, matched group variable light source adopts nature light, and other conditions are constant, and experimental group is apparently higher than the antibacterial efficiency of matched group (see table 2).
Embodiment 3
Weigh up each constituent content according to table 2,0.0001% photosensitive molecular solution is mixed with 1% piroctone olamine salt and moisture, after fully dissolving, supply excess water, regulate pH to 9, at 1000J/cm2Under light intensity, under 600nm wavelength, anaerobic species, the antibacterial efficiency of fungus being reached 99%, matched group variable light source adopts nature light, and other conditions are constant, and experimental group is apparently higher than the antibacterial efficiency of matched group (see table 2).
Embodiment 4
Weigh up each constituent content according to table 2,10% photosensitive molecular solution is mixed with 0.0001% piroctone olamine salt and moisture, after fully dissolving, supply excess water, regulate pH to 5, at 0.1J/cm2Under light intensity, under 400nm wavelength, anaerobic species, the antibacterial efficiency of fungus being reached 99%, matched group variable light source adopts nature light, and other conditions are constant, and experimental group is apparently higher than the antibacterial efficiency of matched group (see table 2).
Embodiment 5
Weigh up each constituent content according to table 2 to be mixed with 0.5% piroctone olamine salt and moisture by 10% photosensitive molecular solution, after fully dissolving, supply excess water, regulate pH to 7, at 100J/cm2Under light intensity, under 600nm wavelength, anaerobic species, the antibacterial efficiency of fungus being reached 99%, matched group variable light source adopts nature light, and other conditions are constant, and experimental group is apparently higher than the antibacterial efficiency of matched group (see table 2).
Embodiment 6
Weigh up each constituent content according to table 2,10% photosensitive molecular solution is mixed with 1% piroctone olamine salt and moisture, after fully dissolving, supply excess water, regulate pH to 9, at 1000J/cm2Under light intensity, under 600nm wavelength, anaerobic species, the antibacterial efficiency of fungus being reached 99%, matched group variable light source adopts nature light, and other conditions are constant, and experimental group is apparently higher than the antibacterial efficiency of matched group (see table 2).
Embodiment 7
Weigh up each constituent content according to table 2,50% photosensitive molecular solution is mixed with 0.0001% piroctone olamine salt and moisture, after fully dissolving, supply excess water, regulate pH to 5, at 0.1J/cm2Under light intensity, under 600nm wavelength, anaerobic species, the antibacterial efficiency of fungus being reached 99%, matched group variable light source adopts nature light, and other conditions are constant, and experimental group is apparently higher than the antibacterial efficiency of matched group (see table 2).
Embodiment 8
Weigh up each constituent content according to table 2 to be mixed with 0.5% piroctone olamine salt and moisture by 50% photosensitive molecular solution, after fully dissolving, supply excess water, regulate pH to 7, at 100J/cm2Under light intensity, under 600nm wavelength, anaerobic species, the antibacterial efficiency of fungus being reached 99%, matched group variable light source adopts nature light, and other conditions are constant, and experimental group is apparently higher than the antibacterial efficiency of matched group (see table 2).
Embodiment 9
Weigh up each constituent content according to table 2,50% photosensitive molecular solution is mixed with 1% piroctone olamine salt and moisture, after fully dissolving, supply excess water, regulate pH to 9, at 1000J/cm2Under light intensity, under 600nm wavelength, anaerobic species, the antibacterial efficiency of fungus being reached 99%, matched group variable light source adopts nature light, and other conditions are constant, and experimental group is apparently higher than the antibacterial efficiency of matched group (see table 2).
The antimicrobial efficiency of photosensitive molecular light power combination under the different light source of table 3
The antimicrobial efficiency of the light power combination of the compositions of the photosensitive molecular of table 4 different component content
Embodiment 1-9 demonstrates the intensity of light source, light application time, pH for the impact of system, determine the optimum range suitable in system, the present invention will be described for 1-9 in conjunction with specific embodiments, for the intensity of illumination (0.1-1000J/CM of the pH condition of light power combination of photosensitive molecular in right, photosensitizer illumination2), pH condition (5-9) and light irradiation time (1min-10min) be suitable for this system, system antibacterial effect efficiency reaches 99% (being specifically shown in table 4), and system antibacterial effect agreement with experimental meets Ministry of Public Health (2002) disinfection technology standard and requires stripping property bacteriostatic test standard.
Embodiment 10
There is the light power combination of compositions of the photosensitive molecular therapeutic effect to acne.
Clinical investigation phase is entered by the light power combination of the compositions of the photosensitive molecular in embodiment 1-9, the patient implementing treatment has 50 examples, wherein there are 20 male and 30 women (18 years old age or more than), face side is not smeared containing photosensitizer photosensitive molecular compositions, and opposite side is smeared and combined ordinary cosmetics without photosensitizer photosensitive molecular.This research evaluation after having smeared the compositions of photosensitive molecular, the effectiveness that carries out after using up irradiation and safety evaluation.Also have rated further the compositions of photosensitive molecular smear with illumination be utilized in conjunction with treatment acne effect.Patient is situation before the treatment: acne is red and swollen, indivedual abscess, and wash one's face pain, and patient has smeared the composition solution of the photosensitive molecular in embodiment 1-9 in half side face acne spots first time, irradiates 2min through LED light；Next day, the composition solution of the photosensitive molecular in embodiment 1-9 is smeared rear small pox and is significantly reduced, and continues to smear embodiment 1-9 acne-removing composition, irradiates 2min through LED light.Third time is observed small pox great majority by fanaticism and is disappeared, and continues to smear embodiment 1-9 acne-removing composition, irradiates 2min through LED light.Being observed by fanaticism for 4th time, pox is substantially flat, continues the photosensitive molecular solution smearing in embodiment 1-9, irradiates 2min through LED light.Through 6 physical therapys, pox is flat.Being for 6 times a course for the treatment of, severe acne can suitably increase the course for the treatment of.Matched group is smeared through same, but does not adopt LED light source to irradiate, and small pox does not significantly reduce, and the epidermal structure cicatrix being damaged does not significantly reduce.
Although the embodiment that disclosed herein is as above, but described content is only the embodiment readily appreciating the present invention and adopt, and is not limited to the present invention.Technical staff in any art of the present invention; under the premise without departing from the spirit and scope that disclosed herein; any amendment and change can be carried out in the form implemented and details, but the scope of patent protection of the present invention, still must be as the criterion with the scope that appending claims defines.
Claims (10)
1. a light power combination for the compositions containing photosensitive molecular, is mainly made up of (1) compositions containing photosensitive molecular, (2) light source.
2. the light power combination of the compositions containing photosensitive molecular according to claim 1, it is characterized in that, described photosensitive molecular is selected from: tartrazines, curcumin, riboflavin 5'-monophosphate sodium salt, lure red AC, new coccine, Chromotrope FB, indigo carmine, erioglaucine disodium salt, fast green FCF, Lissamine green B, naphthol green or acid green, alkermes, Xylene Red azorubine, amaranth, brilliant scarlet G 4R, chlorophyll and copper complex, brilliant black BN (PN), the brown HT of chocolate, beta-carotene, bixin, lycopene, betanin, riboflavin, the red B sodium salt of algae and mixture thereof.
3. the light power combination of the compositions containing photosensitive molecular according to claim 1, it is characterised in that described photosensitive molecular is selected from: sodium copper chlorophllin and derivant, indigo carmine, erioglaucine disodium salt, fast green FCF, Lissamine green B.
4. the light power combination of the compositions containing photosensitive molecular according to claim 1, it is characterized in that, the compositions containing photosensitive molecular is with the weight percent meter of compositions, photosensitive molecular 0.0001%-50%, additive is 0.001%-1%, and all the other are water phosphate buffer.
5. the light power combination of the compositions containing photosensitive molecular according to claim 1, it is characterised in that the wave-length coverage of light source is 400-700nm.
6. the light power combination of the compositions containing photosensitive molecular according to claim 1, it is characterised in that the intensity of light source is 0.1-1000J/cm2。
7. the light power combination of the compositions containing photosensitive molecular according to claim 4, it is characterised in that the composition of additive is the one in piroctone olamine salt, Zinc Pyrithione, climbazole, allantoin.
8. the light power combination of the compositions containing photosensitive molecular according to claim 1, it is characterised in that the proportion of composing containing photosensitive molecular compositions is 50000:1-1:10000.
9. the light power combination of the compositions containing photosensitive molecular described in any one of claim 1-8, the application in germ killing drugs of the light power combination of the wherein said compositions containing photosensitive molecular.
10. the light power combination of the compositions containing photosensitive molecular described in any one of claim 1-8, the light power combination of the wherein said compositions containing photosensitive molecular is in the application in abundance type acne treatment drug.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106539696A (en) * | 2016-12-07 | 2017-03-29 | 江南大学 | The application of 5 aminolevulinic acids |
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| CN105163759A (en) * | 2013-03-14 | 2015-12-16 | 克洛克斯科技公司 | Biophotonic materials and uses thereof |
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| CN105163759A (en) * | 2013-03-14 | 2015-12-16 | 克洛克斯科技公司 | Biophotonic materials and uses thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106539696A (en) * | 2016-12-07 | 2017-03-29 | 江南大学 | The application of 5 aminolevulinic acids |
| CN106539696B (en) * | 2016-12-07 | 2019-07-23 | 江南大学 | The application of 5-ALA |
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Application publication date: 20160720 |