CN1247227C - External-use liposome prepn for treating mite-borne dermatosis - Google Patents
External-use liposome prepn for treating mite-borne dermatosis Download PDFInfo
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- CN1247227C CN1247227C CN 01107203 CN01107203A CN1247227C CN 1247227 C CN1247227 C CN 1247227C CN 01107203 CN01107203 CN 01107203 CN 01107203 A CN01107203 A CN 01107203A CN 1247227 C CN1247227 C CN 1247227C
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Abstract
The present invention relates to an external-use liposome preparation with a herbaceous plant, namely rhubarb extract and metronidazole as main active ingredients, which is used for treating mite dermatosis infected and initiated by skin mites. The external-use liposome preparation has outstanding curative effect on treating common dermatosis such as acarodermatitis, acarian acne, ' rosacea ', etc., has good skin dependence and receptivity and does not have irritation and toxic or side effect. The external-use liposome preparation has the advantages of simple and convenient preparation process, proper preparation cost and no industrial pollution. The present invention is favorable for industrial enlargement.
Description
The present invention is a kind of external-use liposome preparation that is used for the treatment of the demodicid mite dermatosis of cutaneous mites infection initiation.
The vermiform mite of parasitic human body skin claims acarid or demodex folliculorum again, according to the parasitic site difference, is divided into demodex folliculorum and sebaceous gland vermiform mite.Vermiform mite parasitizes the hair follicle and the sebaceous gland of human body skin, and by its mechanical stimulus, effect such as chemical erosion destroys the normal morphology structure and the physiological function of parasitic microenvironment.Clinical and epidemiological study data is indicated when acarid superinfection in a large number, when body local immunity reduces, can cause serious dermal pathology to change, cause the various skin illness, as " rosacea ", acarine acne and acarodermatitis etc. cause whelk, corse sweat pore, pachylosis, clinical symptoms such as sebum secretion increases are destroyed the performance of skin normal appearance, diminish appearance.Along with modern medicine to the transformation of social mentality's pattern and the progressively raising of people's living standard, this type of disease is given the huge psychic trauma that the patient brought simultaneously, more people pay close attention to.Deeply inquire into the infection genesis mechanism of skin demodicidosis, screen miticide efficiently, formulate effectively anti-demodicid mite measure, become the research focus of dermatozoon and dermatological.
Being used for the treatment of the dermatosis method of cutaneous mites due to infecting at present can be by medicines such as metronidazole for oral administration or piperanitrozoles.But after taking above-mentioned medicine side effect is in various degree arranged all, the especially severe person may cause leukopenia.Find that simultaneously above-mentioned two kinds of medicines easily induce acarid to produce drug dependence, influence therapeutic effect.In addition, now patent and the bibliographical information oral drugs that are used for the treatment of acarodermatitis have quinoline, praziquantel, and tetracycline, the ethamine pyridine, agrimonine etc., but curative effect is all undesirable.The medicine for external use that is used for the treatment of acarodermatitis and demodicid mite property " rosacea " both at home and abroad mainly contains sulfur, ammoniated mercury, benzoic acid six fat, benzoyl peroxide, D.D.T, 666.D.D.V. etc.Recently, many extracted form natural plant compositions also find to have external obvious acaricidal activity, but just the time spent curative effect is preferable, and demodicid mite property drug resistance takes place for inefficacy more later on.
Though being used for the treatment of the acarodermatitis curative effect, external metronidazole chloromycetin alcoholic solution determines that tangible stimulation is arranged in being to use, decortication, and erubescence, twinge and part patient are to salicylic acid wherein, the side effect hypersensitive of compositions such as ethanol.Patient's acceptance level is low, is difficult to adhere to the course of treatment, and thoroughly treatment causes palindromia.Nielsen etc. have reported the metronidazole external of 2% cream cream type in British J.of Dermatology 108:327-332 (1983), be used for the treatment of acarodermatitis.Clinical observation finds that this medicine may cause the skin excitation, twinge, burn feeling and dry discomfort etc.Simultaneously, some patient is difficult to accept for the oiliness composition in the preparation, and the smegma of pipe skin causes symptoms such as acne more.In order to overcome above defective, United States Patent (USP) has reported that utilizing Metrogel to be used for the treatment of cutaneous mites infects the various skin disease that causes for No. 4837378.But because the bioactive molecule metronidazole in the said preparation is a full water-soluble, being difficult to effectively see through the fat composition is main epiderm skin, so lower in local skin zone bioavailability after the medicine external.Now gone on the market and the demodicid mite dermal application preparation that kills of clinical practice still in use exists many application limitations and defective.At first, most effectively kill the acaricidal composition extensive uses, induced the vermiform mite drug resistance phenomenon of part, give and effectively treat and prevent that symptomatic recurrence from bringing difficulty.Secondly, because the special dissection and the physiological characteristics of skin, effective ingredient is difficult to high concentration effect vermiform mite parasitic site, becomes to induce the drug-fast major reason of vermiform mite.Decline is killed demodicid mite local skin external preparation and is contained skin irritation and excitation composition, influencing the patient greatly uses acceptance level and adheres to complete sum effective course of treatment, thereby reduce the completeness and the integrity of treatment, giving effectively, the demodectic infection of radical cure brings objective difficulty.Therefore in order to increase the local topical bioavailability of medicament, increase therapeutic index, reduce the medication side effect, multiple mode is used improves treatment acarodermatitis efficiency of drugs.
The purpose of this invention is to provide the external-use liposome preparation that a kind of more effective treatment cutaneous mites infects.Not only therapeutic efficacy is higher for it, and safety, has no side effect, and uses comfortable.
Solution of the present invention is based on understanding and the Therapeutic Principle's raising and the improvement of the genesis mechanism that cutaneous mites is infected, employing contains bag by the Liposomal formulation of several active component, promptly utilize the special transdermal characteristic of liposome, had killing and suppressed natural plants Radix Et Rhizoma Rhei extract and the chemicals molecule metronidazole that cutaneous mites is grown by its bag, by the active drug molecule of its bag quilt of the slower release of liposome, effectively improve the activity of effective active composition in the skin follicle sebaceous gland microenvironment of acarid parasitism.Can be worked in coordination with adduction by the liposome bag by two active substances simultaneously and bring into play its both demodicid mite extremely, antiinflammatory suppresses the effect of the harmful causal organism of skin.
Medicine of the present invention is prepared by following component: (consumption is weight percentage)
Plant Radix Et Rhizoma Rhei extract 2-20% phosphatidylcholine 0.05-10%
PHOSPHATIDYL ETHANOLAMINE 0.05-5% cholesterol 0.2-10%
Metronidazole 0.05-5% buffer agent surplus.
The preferred percentage by weight of the prescription of preparation medicine of the present invention is:
Plant Radix Et Rhizoma Rhei extract 3-10% phosphatidylcholine 0.1-5%
PHOSPHATIDYL ETHANOLAMINE 0.1-2% cholesterol 0.5-5%
Metronidazole 0.1-3% buffer agent surplus.
Optimum weight percentage ratio of the present invention is:
Plant Radix Et Rhizoma Rhei extract 5% phosphatidylcholine 1% PHOSPHATIDYL ETHANOLAMINE 0.5%
Cholesterol 0.3% metronidazole 0.3% buffer agent surplus.
Above-mentioned each component is made medicine production method of the present invention is:
1. after getting the root or stem pulverizing of plant Radix Et Rhizoma Rhei, do organic solvent with methanol, 50 ℃-70 ℃ circulations were extracted 2 hours in cable-styled fat-extraction device.Organic extracting solution decompression is low-temperature evaporation down, and 65 ℃ of temperature oven dryings of residual solvent get extract.
2. Radix Et Rhizoma Rhei extract, gram phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, cholesterol and metronidazole are dissolved in methanol solution, mixture solution is in 0.08m Pa negative pressure, under 40 ℃, and decompression rotation evaporation in 5 hours organic solution.Add buffer solution in the container, on reciprocating type oscillator, shook 2 hours immediately, obtain the little liquid formulation that viscosity is arranged of white.Can add an amount of suitable antiseptic, thickening agent, colouration agent and spice are promptly made medicine of the present invention.
The embodiment of a concrete preparation method of the present invention is: after getting the root or 1 kilogram of pulverizing of stem of Radix Et Rhizoma Rhei, do organic solvent with methanol, 50 ℃-70 ℃ circulations were extracted 2 hours in cable-styled fat-extraction device.Organic extracting solution decompression is low-temperature evaporation down, and 65 ℃ of temperature oven dryings of residual solvent get 50 gram extracts.With Radix Et Rhizoma Rhei extract, 10 gram phosphatidylcholines, 10 gram PHOSPHATIDYL ETHANOLAMINE, 5 gram cholesterol and 3 gram metronidazoles are dissolved in 200 ml methanol solution, and mixture solution is in 0.08m Pa negative pressure, under 40 ℃, decompression rotation evaporation in 5 hours organic solution.Add 1 liter in buffer solution in the container, on reciprocating type oscillator, shook 2 hours immediately, obtain the little liquid formulation that viscosity is arranged of white.
The plant Radix Et Rhizoma Rhei that is adopted in the said method comprises Rheum officinale, Rheum tanguticum and goose palm Radix Et Rhizoma Rhei.
Clinical observation result proves that external-use liposome preparation of the present invention is better than external preparation commonly used at present at the dermatosis that the treatment acarid causes, and safe, no obvious toxic and side effects.
An important feature of the present invention is to utilize the local topical liposome active drug molecule enrichment need be able to be brought into play the skin area of drug effect, under the prerequisite that does not affect the treatment, can effectively reduce the concentration of each active component in the external preparation, reduction may be in the medication process contingent skin irritation, swash and if probability hypersensitive, lower risk.Can effectively reduce simultaneously the frequency of utilization of external preparation, make medication more convenient, more comfortable.
The liposome that another important feature of the present invention is to use wraps in preparation process by a certain amount of moisture, contact with the phospholipid layer of skin surface is affine by liposome, can replenish the moisture content of skin surface loses, to keeping skin appropriateness moisture, reduce the skin surface roughness, improve skin appearance, have the crease-resistant effect of tangible skin-protecting face nursing.The skin surface phospholipid layer provides skin normal physiologic barrier function, because the influence of inherent and extraneous factor, the integrity of its structure and composition may cause destruction.Deficiency by the mode of local topical Liposomal formulation can be replenished skin surface phospholipid plays an important role for recovering the normal physiological status of skin.
The present invention utilizes liposome to be coated on confirmation has the usefulness of obviously tagging to the human Demodex that exsomatizes in the experiment in vitro natural plants Radix Et Rhizoma Rhei organic extract and chemosynthesis molecule metronidazole, and the preparation of the treatment acarodermatitis of local topical is finished in preparation.Said preparation can be used for the various skin disease relevant with mite infection, comprises acarine acne, acarine perioral dermatitis, " rosacea " and acarine blepharitis.Simultaneously acne vulgaris also there is obvious curative effects.
In addition, owing to do not contain the oil-phase component of alcoholic solution and generation greasy feeling in the liposome external curing demodicid mite property skin infection pharmaceutical formulation of the present invention, skin is produced can not produce stimulation, in use, increase the comfort level of external, improved the acceptance of the external of preparation, be beneficial to popularization.
The Liposomal formulation of external curing demodicid mite property skin infection of the present invention, preparation technology is simple, and cost is lower.Topical agent technology by knowing can be used as the water in the prescription, is prepared into multiple exterior-applied formulation, as cream, and unguentum, lotion and gel.
Clinical experiment effect of the present invention is as follows: with at random, contrast principle design clinical experiment scheme.In order to investigate the clinical effectiveness that externally used compound Liposomal formulation of the present invention is used for the treatment of the acarid skin infection, patient's (24.2 years old mean age) that 66 clinical and laboratory diagnosises are acarodermatitis participate in this by a definite date 2 weeks at random, the experiment of contrast clinical treatment.Matched group adopts 2% metronidazole chloromycetin alcoholic solution of clinical experiment unit's extensive use.To observe the patient and be divided into two groups at random, 39 of first groups are used externally used compound Liposomal formulation of the present invention.27 of second groups are used 2% metronidazole chloromycetin alcoholic solution.Before the patient who carries out clinical observation enters this treatment January, all there are not system and local medication history.First group patient follows the doctor's advice, and in facial neutral soap in evening every day, after warm water cleans, externally used compound Liposomal formulation of the present invention is coated with and suffers from the district.The second group is used 2% metronidazole chloromycetin alcoholic solution according to conventional method, and every day sooner or later respectively once.By to facial inflammatory lesion skin lesion, the classification of keeping the score of non-inflammatory lesions skin lesion is respectively at 0,3,7,14 days four times records of medication.To the excitement of patient in the use to two kinds of preparations, dry sensation, sensation of pricking have carried out contrast scoring and calibration laboratory observation simultaneously.Two groups of clinical indexes are by pairing T check carrying out statistical analysis.Clinical observation result is analyzed as follows: first group patient, in facial neutral soap in evening every day, after warm water cleans, externally used compound Liposomal formulation of the present invention is coated with and suffers from the district, after one all medications finish, the average skin lesion rate of going down is that the average skin lesion rate of going down was 87.5% after 67.5%, two all medications finished, and second group patient, use 2% metronidazole chloromycetin alcoholic solution according to conventional method, every day sooner or later each once, after all medications finish, the average skin lesion rate of going down is 31.4%, after two all medications finished, the average skin lesion rate of going down was that 51.4%, two group of curative effect relatively has significant difference (p＜0.05).Find of the present inventionly for the facial skin lesion of inflammatory simultaneously, the compound recipe Liposomal formulation of this invention has more effective than 2% metronidazole chloromycetin alcoholic solution.(95%vs 75%) clinical observation material proves that external-use liposome preparation of the present invention is better than present common dosage forms at the dermatosis that treatment acarid skin infection causes, and safe, has no side effect.
Safety for the Liposomal formulation of estimating external curing demodicid mite property skin infection of the present invention designs following skin acute toxicity test.Select about body weight 300 grams, skin smooth, not damaged does not have 20 of dermopathic Cavia porcelluss.Cavia porcellus is being tried preceding 24 hours backs both sides unhairing 40cm2.Wherein a side is made " well " font with the sterile surgical cutter and is scratched epidermis, slight oozing of blood degree of being occurs with skin.1 gram external-use liposome preparation of the present invention directly is applied to plucked complete sum damaged skin.10 preparations that use typical concentrations wherein, other 10 preparations (Radix Et Rhizoma Rhei extract 15%, metronidazole 1.5%) that use 3 times of typical concentrations.Give and to be tried behind the thing 24 hours, do not see and be poisoned to death.Continue to observe, continuous seven days, all animal subject outward appearance behaviors, abnormal motion, the mental status, appetite, stool, indexs such as breathing are all no abnormal.According to the result of above skin acute toxicity testing, can point out external-use liposome preparation of the present invention not have acute dermal toxicity, have higher safety.
Claims (4)
1, a kind of external-use liposome preparation for the treatment of mite-borne dermatosis is characterized in that medicine prepared by following components in weight percentage:
Methanolic extract 2～20% phosphatidylcholines 0.05～10% of plant Radix Et Rhizoma Rhei
PHOSPHATIDYL ETHANOLAMINE 0.05～5% cholesterol 0.2～10%
Metronidazole 0.05～5% buffer agent surplus.
2, the external-use liposome preparation of treatment mite-borne dermatosis according to claim 1 is characterized in that: the percentage by weight of each component is:
Methanolic extract 3～10% phosphatidylcholines 0.1～5% of plant Radix Et Rhizoma Rhei
PHOSPHATIDYL ETHANOLAMINE 0.1～2% cholesterol 0.5～5%
Metronidazole 0.1～3% buffer agent surplus.
3, the external-use liposome preparation of treatment mite-borne dermatosis according to claim 1 is characterized in that: the percentage by weight of each component is: the methanolic extract 5% of plant Radix Et Rhizoma Rhei, phosphatidylcholine 1%, PHOSPHATIDYL ETHANOLAMINE 0.5%, cholesterol 0.3%, metronidazole 0.3%, buffer agent surplus.
4, the external-use liposome preparation of treatment mite-borne dermatosis according to claim 1 is characterized in that: described external-use liposome preparation can be prepared into cream or unguentum or lotion or gel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01107203 CN1247227C (en) | 2001-02-26 | 2001-02-26 | External-use liposome prepn for treating mite-borne dermatosis |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01107203 CN1247227C (en) | 2001-02-26 | 2001-02-26 | External-use liposome prepn for treating mite-borne dermatosis |
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| CN1312105A CN1312105A (en) | 2001-09-12 |
| CN1247227C true CN1247227C (en) | 2006-03-29 |
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| CN 01107203 Expired - Fee Related CN1247227C (en) | 2001-02-26 | 2001-02-26 | External-use liposome prepn for treating mite-borne dermatosis |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102151302A (en) * | 2010-02-11 | 2011-08-17 | 四川大学华西医院 | Externally-applied rhubarb liposome and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102846730A (en) * | 2012-10-08 | 2013-01-02 | 成都中医药大学 | Extractive for official rheum seed and identification method for official rheum seed |
| CN105963698A (en) * | 2016-05-29 | 2016-09-28 | 金新 | Ointment for photochemical adjuvant therapy and preparation method and application thereof |
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2001
- 2001-02-26 CN CN 01107203 patent/CN1247227C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102151302A (en) * | 2010-02-11 | 2011-08-17 | 四川大学华西医院 | Externally-applied rhubarb liposome and preparation method and application thereof |
| CN102151302B (en) * | 2010-02-11 | 2012-07-04 | 四川大学华西医院 | Externally-applied rhubarb liposome and preparation method and application thereof |
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| Publication number | Publication date |
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| CN1312105A (en) | 2001-09-12 |
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