CN103417966B - Hydrochloric acid aminolevulinic acid liniment and preparation technology thereof - Google Patents

Hydrochloric acid aminolevulinic acid liniment and preparation technology thereof Download PDF

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Publication number
CN103417966B
CN103417966B CN201310374599.0A CN201310374599A CN103417966B CN 103417966 B CN103417966 B CN 103417966B CN 201310374599 A CN201310374599 A CN 201310374599A CN 103417966 B CN103417966 B CN 103417966B
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liniment
powder
solvent
radix
filtrate
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CN103417966A (en
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林凡友
林凡儒
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Xiang Yu Pharmaceutical limited company
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SHANDONG XIANGYU HEALTH PHARMACEUTICAL CO Ltd
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Abstract

The invention belongs to the medical technology filed and discloses a hydrochloric acid aminolevulinic acid liniment which is composed of a powder agent and a solvent. When the hydrochloric acid aminolevulinic acid liniment is used, the powder agent and the solvent are dissolved by matching with each other. The invention further discloses a preparation method of the hydrochloric acid aminolevulinic acid liniment. The prepared hydrochloric acid aminolevulinic acid liniment is good in effect of treating acne, free of toxic side effects, simple in manufacturing method and wide in application prospect.

Description

A kind of 5-ALA liniment and preparation technology thereof
Technical field
The invention belongs to medical technical field, relate to a kind of 5-ALA liniment and preparation technology thereof.
Background technology
Acne is a kind of multifactorial disease, and its morbidity is main and sex hormone level, sebaceous gland are secreted in a large number, propionibacterium acnes propagation, the factor analysis such as the dyskeratosis of pilosebaceous duct and inflammation.Acne is apt to occur in hebetic masculinity and femininity, and male is slightly more than women, but women's morbidity is early than male.Have the teenager of 80-90% to suffer from acne, after adolescence, often can naturally go down or fully recover, indivedual patients also can extend to more than 30 years old.Although acne is the disease that has spontaneous recovery tendency, acne itself and acne treatment cause not in time cicatrixcan have a strong impact on patient's quality of life, cause patient's stress and financial burden, need cause concern.Acne is apt to occur in buccal, forehead, buccal and nasolabial fold, is secondly chest, back and shoulder.The general no conscious sympton of acne lesions, can, with pain, be divided into acne, pimple, pustule and cyst tuberosity etc. when inflammation is obvious
Acne is an easily disease for recurrence, and the fluctuation of state of an illness weight own is indefinite.Affect acne factor a lot, single therapy is often difficult to receive good effect, need to take Comprehensive Treatment according to the state of an illness.First to adjust phychology, keep actively optimistic state; Eat less pungent greasy food and sweet food, these food all can stimulate fuel-displaced, increase the weight of acne; Eat vegetable and fruit more, keep free movement of the bowels also very important.In addition, select suitable facial cleansing agent and wetting agent according to skin type, and form good washing and protect custom, too not remove oils and fats and do not protect, cause skin too dry, skin barrier function is impaired, also can increase the weight of to a certain extent acne.Adhere to external medication when symptom is lighter, during severe symptoms, add oral drugs and control, to shorten the natural history of acne, reduce its probability that sequela occurs (pox prints and pox scar).External used medicine comprises tretinoin medicines and the lincomycin for the treatment of acne, benzoyl peroxide etc.Oral drugs: middle severe acne can Combined with Oral azithromycin etc. antibiotic medicine.Antibiotic controls inflammation rapidly effectively, but does not prevent the effect of recurrence.Severe acne can be taken Tai Ersi.Can adopt and start the method for drug administration of successively decreasing, or adopt the treatment of median dose position.Long-term taking antibiotic can produce larger drug resistance and toxic and side effects to body, and can not effect a radical cure acne.
5-ALA (ALAHCl) has another name called 5-ALA hydrochlorate, is the second filial generation photosensitizer of just having developed in recent years, is optical dynamic therapy medicine.In December, 2000, Gai Yaoyi U.S. official listing, is used for the treatment of face and the non-hyperkeratotic actinic keratosis of scalp.Meanwhile, the said firm started to treat with ALA-PDT the clinical trial of common acne in 1996, the existing II clinical trial phase that carrying out.Acne is a kind of dermatosis that affects 80% above adolescent, propionibacterium acne bacterium (Propionibacterium acnes) and sebum secretion play a major role in the morbidity of acne, present stage, primary treatment method was with the treatment of antibiotic and tretinoin medicine, but this bacterium is to antibiotic drug resistance gradually, and although tretinoin medicine is useful to the state of an illness, but having potential teratogenesis, is not very desirable.5-ALA liniment associating optical dynamic therapy is as the new treatment means of acne vulgaris, there is the features such as safe and effective, side effect is little, be a kind of very effective Therapeutic Method, in order to ensure people ' s health, to meet the demand growing to this medicine, we determine to develop this medicine.
Summary of the invention
The object of this invention is to provide a kind for the treatment of both the principal and secondary aspects of a disease, have no side effect, safe ready, cheap 5-ALA liniment.Its objective is for effectively treatment and prevention acne, the drug safety that overcomes prior art is poor, the easy defect such as recurrence of pigmentation and drug withdrawal.The present invention also provides the preparation technology of above-mentioned liniment.
For realizing above-mentioned purpose of the present invention, the technical solution used in the present invention is as follows:
A 5-ALA liniment, it is comprised of powder and solvent two parts, described powder is 354mg/ bottle, described solvent is 1.5ml/ bottle, during use by the two molten fitting over together.
Described powder is 5-ALA; Described solvent (1.5ml) is mixed by ethanol 672mg, sodium lauryl sulphate 5mg, PEG400 21mg, propylene glycol 49mg and pure water.
Preferably,
Described powder is that 5-ALA and compound Chinese medicine powder mix according to the weight ratio of 1:1; Described solvent (1.5ml) is mixed by ethanol 672mg, sodium lauryl sulphate 5mg, PEG400 21mg, propylene glycol 49mg and pure water;
Described compound Chinese medicine powder is prepared as follows and forms:
1) get Radix Platycodonis 100g, Cortex Moutan 80g, Radix Saposhnikoviae 80g, Fructus Forsythiae 70g and Radix Puerariae 50g, put in pulverizer and pulverize, take out and be laid into 400cm2, irradiate 10 minutes under ultraviolet, uitraviolet intensity is 2000uW/cm2; Then use the pure water of 2L as solvent, 60 ℃ are hydrolyzed 1 day, filter and collect filtrate; Filtrate is placed in vacuum decker, is concentrated in vacuo to 1/5th of filtrate volume, obtain concentrated solution;
2) take Sargassum 100g, Radix Scutellariae 80g, Radix Rehmanniae 70g, Radix Paeoniae Alba 60g and Radix Glycyrrhizae 50g, mix homogeneously, the decocting that adds 5 times of weight boils 1 hour, filters and collects filtrate, the pH that adjusts filtrate with the hydrochloric acid solution of 1mol/L is 7, then filtrate is condensed into the extractum that density is 1.1g/ml;
3) by step 1) concentrated solution and the step 2 prepared) extractum prepared mixes, and stirs, and is then placed at 70 ℃ after couveuse is dried, and more than being crushed to 200 orders, obtains described compound Chinese medicine powder.
The invention also discloses the preparation technology of above-mentioned liniment.
Usage: powder and solvent, be applied to affected part, parcel lucifuge 4 hours, then 615-645nm red light irradiation affected part is 15 minutes; Once in a week, continuous three weeks.
The main beneficial effect that the present invention obtains is as follows:
Liniment of the present invention adopts Chinese medicine and western medicine set, is equipped with pure Chinese medicine, and the compatibility of each taste Chinese medicine is reasonable, and therapeutic effect is good, have no side effect, and treating both the principal and secondary aspects of a disease, short treating period, acne, is better than 5-ALA liniment of the prior art effectively;
The present invention adopts unique Technology, for different raw materials, adopt different processing modes, select the UV treatment of suitable time and amount of radiation, the effective ingredient in raw material is discharged to greatest extent, the nutritional labeling waste of having avoided single processing mode to cause; And extraction step is simple to operate, be applicable to suitability for industrialized production, possess wide application prospect;
The adjuvant that the present invention selects is reasonable, and pure water is mainly as the solvent of principal agent; Ethanol, as penetrating agent, antiseptic, can increase drug osmotic effect, thereby improves the absorption of medicine, and has certain antisepsis; PEG400 is done cosolvent and stabilizing agent; Sodium lauryl sulphate is done penetrating agent; Propylene glycol has moisturizing, antisepsis.
The specific embodiment
Below employing specific embodiment is made to further explanation to the present invention, but it is not as the restriction to initiative spirit of the present invention.
Embodiment 1
A 5-ALA liniment, it is comprised of powder and solvent two parts, powder is 354mg/ bottle, solvent is 1.5ml/ bottle, during use by the two molten fitting over together; Powder is 5-ALA powder; Solvent (1.5ml) is mixed by ethanol 672mg, sodium lauryl sulphate 5mg, PEG400 21mg, propylene glycol 49mg and pure water; The preparation method of solvent is as follows: ethanol 672mg, sodium lauryl sulphate 5mg, PEG400 21mg, propylene glycol 49mg are added in container, then add appropriate pure water standardize solution to 1.5ml.
Method of application: powder and solvent, be applied to affected part, parcel lucifuge 4 hours, then 615-645nm red light irradiation affected part is 15 minutes; Once in a week, continuous three weeks.
Embodiment 2
A 5-ALA liniment, it is comprised of powder and solvent two parts, powder is 354mg/ bottle, solvent is 1.5ml/ bottle, during use by the two molten fitting over together; Powder is that 5-ALA powder and compound Chinese medicine powder mix according to the weight ratio of 1:1; Solvent (1.5ml) is mixed by ethanol 672mg, sodium lauryl sulphate 5mg, PEG400 21mg, propylene glycol 49mg and pure water; The preparation method of solvent is as follows: ethanol 672mg, sodium lauryl sulphate 5mg, PEG400 21mg, propylene glycol 49mg are added in container, then add appropriate pure water standardize solution to 1.5ml;
Above-mentioned compound Chinese medicine powder is prepared as follows and forms:
1) get Radix Platycodonis 100g, Cortex Moutan 80g, Radix Saposhnikoviae 80g, Fructus Forsythiae 70g and Radix Puerariae 50g, put in pulverizer and pulverize, take out and be laid into 400cm 2, under ultraviolet, irradiating 10 minutes, uitraviolet intensity is 2000uW/cm 2; Then use the pure water of 2L as solvent, 60 ℃ are hydrolyzed 1 day, filter and collect filtrate; Filtrate is placed in vacuum decker, is concentrated in vacuo to 1/5th of filtrate volume, obtain concentrated solution;
2) take Sargassum 100g, Radix Scutellariae 80g, Radix Rehmanniae 70g, Radix Paeoniae Alba 60g and Radix Glycyrrhizae 50g, mix homogeneously, the decocting that adds 5 times of weight boils 1 hour, filters and collects filtrate, the pH that adjusts filtrate with the hydrochloric acid solution of 1mol/L is 7, then filtrate is condensed into the extractum that density is 1.1g/ml;
3) by step 1) concentrated solution and the step 2 prepared) extractum prepared mixes, and stirs, and is then placed at 70 ℃ after couveuse is dried, and more than being crushed to 200 orders, obtains described compound Chinese medicine powder.
Method of application: powder and solvent, be applied to affected part, parcel lucifuge 4 hours, then 615-645nm red light irradiation affected part is 15 minutes; Once in a week, continuous three weeks.
Embodiment 3
The zoology effect of the liniment of embodiment 1 and 2 preparations:
Animal is selected: 60 of new zealand rabbits, and male and female half and half, body weight is 2.2 ± 0.3kg;
Experimental design: select at random 50 rabbit, in every rabbit right in ear side syrinx opening part preserved skin 2cm * 2cm scope, with the even coating 50% oleic acid 0.5mL of syringe, 1 time/d, continuous 2 weeks, after coating the 12nd day, the wide intradermal injection density 10 of auris dextra 9the propionibacterium acnes liquid 200 μ L of individual/mL, and mark in injection place.In the 15th day, evaluation model formational situation, occur that following symptom is modeling success: red swelling of the skin, slightly thick, follicular orifice protuberance is pimple shape, rough surface, that touches is hard like acneform, and microscopy hair follicle surrounding cuticular layer obviously thickens, be full of pink keratinization thing in enlarged areas, chamber, sebaceous gland increases obviously, consistent with mankind's acne symptom.Choose 40 of the successful rabbit of modeling, be divided into model control group, control drug group, 1 group of embodiment, 2 groups of embodiment; 10 of modeling is not blank group.
1 group of administering mode: embodiment: solvent is extracted out with syringe, inject powder, vibration is dissolved it, and the cotton balls (dose 2mL) that soaks full medicinal liquid by suitable size covers affected part completely, then covers lucifuge with the aluminium foil that is greater than cotton balls, immobilization with adhesive tape, after lucifuge 2h, clear water cleans affected part, wipe away dry after, use He-Ne laser therapeutic apparatus (wavelength 632nm, power 150mW/cm 2), optical fiber head is apart from skin lesion 10mm, vertical irradiation, and the about 4mm of spot diameter, irradiates 20min; Weekly, continuous three weeks.2 groups of processing modes of embodiment are with 1 group of embodiment.Model control group: the solvent part of an affected part liniment, simulated light dynamic therapy, 1 time/week, is used in conjunction 3 weeks.Control drug group: affected part is coated with clindamycin and metronidazole liniment, each 1 time sooner or later, is used in conjunction 3 weeks.Concrete therapeutic outcome is in Table 1:
Table 1
Conclusion:
2 groups of therapeutic effect of embodiment 1 and embodiment are remarkable, can significantly improve the size of sebaceous gland and hair follicle, effectively suppressed the generation of acne dermatitis, are better than prior art routine administration; And find, 2 groups of embodiment, therapeutic effect is obviously better than 1 group of embodiment.
Embodiment 4
Transdermal absorption factor test:
Adopt new zealand rabbit, be divided into two groups, 10 every group; With syringe, solvent is extracted out, injected powder, vibration is dissolved it, and the cotton balls that soaks full medicinal liquid by suitable size covers auris dextra medial surface completely, then covers lucifuge with the aluminium foil that is greater than cotton balls, and immobilization with adhesive tape, after lucifuge 2h, detects absorbance; I: (solvent formula of the ALA liniment of U.S.'s listing is (w/w) to external ALA liniment listing product formula: 39.9%-48.8% ethanol, 39.1%-47.8% pure water, 5.9%-7.4% lauryl alcohol, 3.5%-4.3% isopropyl alcohol, 1.5-1.8% Polyethylene Glycol) and II: the transdermal absorption factor measurement result of liniment formula of the present invention (embodiment 2) is as following table 2:
Table 2
Time (min) 15 30 45 60 90 120
(I) transdermal absorption factor (%) 5.9 26.7 36.7 54.6 75.5 84.5
(II) transdermal absorption factor (%) 7.2 33.2 43.9 57 76 88.5
Result of the test shows, the Transdermal absorption situation of two kinds of formulas is all relatively good, and the assimilation effect of the embodiment of the present invention 2 is more better than matched group, and it is rational that the prescription that proves the 5-ALA liniment of the present invention's development forms.
Although, above used general explanation, the specific embodiment and test, the present invention is described in detail, on basis of the present invention, can make some modifications or improvements it, and this will be apparent to those skilled in the art.Therefore, these modifications or improvements, all belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.

Claims (2)

1. a 5-ALA liniment, is characterized in that, described liniment is comprised of powder and solvent two parts, and described powder is 354mg/ bottle, and described solvent is 1.5ml/ bottle, during use by the two molten fitting over together;
Described powder is that 5-ALA powder and compound Chinese medicine powder mix according to the weight ratio of 1:1; Described solvent is mixed by ethanol 672mg, sodium lauryl sulphate 5mg, PEG400 21mg, propylene glycol 49mg and pure water; The preparation method of described solvent is as follows: ethanol 672mg, sodium lauryl sulphate 5mg, PEG400 21mg, propylene glycol 49mg are added in container, then add appropriate pure water standardize solution to 1.5ml;
Described compound Chinese medicine powder is prepared as follows and forms:
1) get Radix Platycodonis 100g, Cortex Moutan 80g, Radix Saposhnikoviae 80g, Fructus Forsythiae 70g and Radix Puerariae 50g, put in pulverizer and pulverize, take out and be laid into 400cm 2, under ultraviolet, irradiating 10 minutes, uitraviolet intensity is 2000 μ W/cm 2; Then use the pure water of 2L as solvent, 60 ℃ are hydrolyzed 1 day, filter and collect filtrate; Filtrate is placed in vacuum decker, is concentrated in vacuo to 1/5th of filtrate volume, obtain concentrated solution;
2) take Sargassum 100g, Radix Scutellariae 80g, Radix Rehmanniae 70g, Radix Paeoniae Alba 60g and Radix Glycyrrhizae 50g, mix homogeneously, the decocting that adds 5 times of weight boils 1 hour, filters and collects filtrate, the pH that adjusts filtrate with the hydrochloric acid solution of 1mol/L is 7, then filtrate is condensed into the extractum that density is 1.1g/ml;
3) by step 1) concentrated solution and the step 2 prepared) extractum prepared mixes, and stirs, and is then placed at 70 ℃ after couveuse is dried, and more than being crushed to 200 orders, obtains described compound Chinese medicine powder.
2. the application of liniment as claimed in claim 1 in preparing the medicine of Acne treatment.
CN201310374599.0A 2013-08-23 2013-08-23 Hydrochloric acid aminolevulinic acid liniment and preparation technology thereof Expired - Fee Related CN103417966B (en)

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CN103816539B (en) * 2014-03-18 2015-07-22 翔宇药业股份有限公司 Medicinal composition containing aminolevulinic acid
CN103816116B (en) * 2014-03-18 2015-07-08 翔宇药业股份有限公司 Medicament for treating skin cancer and preparation method thereof
CN103860535B (en) * 2014-03-19 2015-09-23 翔宇药业股份有限公司 A kind of 5-ALA liniment

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