CN1035355C - Preparing method for coating agent of complex triamcinolone acetonide acetate - Google Patents

Abstract

The present invention discloses a preparation method of compound triamcinolone acetonide film coating agents, which is called a skin treating film in short. Because medicine belonging to cortical hormone and antibiotic is reasonably used in a prescription, the skin treating film is suitable for psoriasis, neurodermatitis, chronic eczema, etc. After compound liquid preparations prepared from skin penetration agents and film forming agents are applied to affected positions especially, solvent parts of compound liquid preparations are rapidly and naturally volatilized, and the compound liquid preparations form a medicine film on the surface of the affected parts by the film forming agents to exert therapeutic effect.

Description

The preparation method of coating agent of complex triamcinolone acetonide acetate

The present invention relates to a kind of medicine for external use, it is the preparation method of coating agent of complex triamcinolone acetonide acetate, be called for short " skin treatment film ", owing to reasonably selected 17-hydroxy-11-dehydrocorticosterone and antibiotics class medicine for use in the prescription, thereby it is existing extensively antibiotic, antiinflammatory, anti-dandruff, itching-relieving action, to psoriasis (psoriasis) neurodermatitis, chronic eczema, lichen planus and various local itching disease all have good efficacy, particularly adopted transdermal agent and film former to make compound liquid preparation, after being applied to affected part, the solvent part is volatilization naturally rapidly, and medicine then forms pharmaceutical film performance therapeutical effect by means of film former on the surface.

The medicine for external use that the treatment dermatosis is used is more, all adopt " wintergreen oil liquid paraffin " and compositions such as " glycerol " to make ointment in most of prescription, its shortcoming is that positions such as head and face should not be coated with, medicine and outside air can not completely cut off and be unfavorable for improving therapeutic effect, main is because medicines such as glycerol are not volatile, bring bigger trouble than thickness, pollution clothes to the patient, somebody's adhesive plaster (zinc oxide) allergy, it is greatest weakness that the women's head-ornaments extremity are coated with that subsides are inconvenient to very much, so easy pollution clothes of frost and ointment formulation, lessen the curative effect, can not quantitatively absorb.

Purpose of the present invention discloses a kind of preparation method of new drug, and its prescription is stable, dosage form is novel, technological process is rationally safe and reliable, forms thin film after the medicine for external use evident in efficacy, welcome by the patient.

Purpose of the present invention can realize by disclosing following scheme:

17-hydroxy-11-dehydrocorticosterone and antibiotic medicine have been adopted in described process and the prescription, it is characterized in that adopting in the preparation process transdermal agent and film former to make compound liquid preparation, the volatilization naturally rapidly of the solvent part of compound liquid preparation, medicine then becomes pharmaceutical film by means of film former on the surface, and its technological process is: the matrix solution preparation

The main solution preparation of → mixing → filtration (chemical examination) → drying → fill → add a cover → pack (chemical examination) → warehouse-in

Described prescription and compound method are as follows:

Triamcinolone 69g ethyl cellulose 1.38kg

Lincomycin hydrochloride 841.5g acetone 10.89kg

(school valency: 820u/mg) ether 9.85kg

Dimethyl sulfoxide 3.036k9 ethanol 58.58kg

Oleum Ricini 690ml

Total amount 100,000 ml (pact);

Adjust:

1) substrate liquid preparation: accurately take by weighing (95%) ethanol of institute's consumption 80%, drop in the jacketed pan standby.Accurately weighing institute consumption ethyl cellulose is put in the enamel bucket, with part surplus ethanol, adds in the cellulose under constantly stirring, brute force stirs into pasty state, after all caking disappears, under agitation adds it in jacketed pan, then to the jacketed pan air feed, for guaranteeing to the greatest extent little volatile quantity, adopt interruptible gas supply in a small amount, stop heating during to 50 ℃ of temperature of liquid, constantly stir, till the ethyl cellulose off-bottom, the cooling of can in interlayer, washing by water, making a pot interior temperature of liquid reduce to 30 ℃ can use;

2) preparation of main liquid: accurately weighing triamcinolone, lincomycin hydrochloride, put and add the ormal weight dimethyl sulfoxide in the suitable molten device, in 70 ℃ of water-baths, heat, constantly stir, the control fluid temperature must not be higher than 50 ℃ to principal agent all till the dissolving;

3) close the liquid preparation: after treating that the cellulose solution temperature is reduced to 30 ℃, under agitation add in the cellulose solution slowly principal agent solution, use the molten device of alcohol flushing of surplus then, acetone, ether with ormal weight adds wherein slowly again, after stirring makes mix homogeneously, do middle product chemical examination, qualified back fill with 100 order silk filtering and samplings.

Good effect of the present invention is: the reasonable preparation novelty of filling a prescription, except that principal agent, adopt penetrating agent and filmogen, after making the external of filming, can form thin film, with isolate from outer air in skin lesion place, can reduce its influence of outer bound pair and increase stability of drug, thereby improve curative effect.

Accompanying drawing 1 illustrates a kind of best enforcement figure of technical process of the present invention.

One, figure mesostroma solution refers to ethanol and the mixed liquid of ethyl cellulose.

Main solution refers to dimethyl sulfoxide, triamcinolone, lincomycin among the figure.

Mixed liquor among the figure: Oleum Ricini, acetone, ether are mixed with main solution with substrate.

Embodiment:

Two, prescription: (thousand)

Triamcinolone 17.25g lincomycin 204g

Dimethyl sulfoxide 690ml Oleum Ricini 172.5ml

Ethyl cellulose 345g ether 3450ml

Acetone 3450ml ethanol 17237.5ml

A 1.000 ≈ 25566.25ml.

Three, dosing:

1, the preparation of matrix solution (first liquid)

Accurately taking by weighing 95% ethanol (except that leaving and taking a little eluant container) all places in the jacketed pan, under constantly stirring, add load weighted ethyl cellulose in the ethanol slowly then, can open the cap relief valve heating edge after eliminating caking stirs, when treating that temperature rises to 45 ℃, stop heating, temperature is the highest to be no more than 50 ℃ (and take interruptible gas supply, impel the ethanol volatilization in order to avoid the pot wall temperature is too high) to all lowering the temperature till the ethyl celluloses dissolving again, treat 35 ℃ of solution temperatures, below can be for using.

2, the preparation of principal agent solution (second liquid)

Accurately taking by weighing dimethyl sulfoxide puts in the enamel bucket, stirring adds in the dimethyl sulfoxide slowly on the limit will to distinguish accurate load weighted omcilon, lincomycin then, be to quicken medicine dissolution, bucket can heat in water-bath and constantly stir the control fluid temperature and can not surpass 45 ℃ and treat that all the dissolving back lowers the temperature standby.

3, the preparation of mixed liquor

Accurately measuring an amount of Oleum Ricini adds in the chilled first liquid under constantly stirring slowly, treat miscible evenly after, continue under agitation to add the acetone of accurately measuring and ether again second liquid input is stirred miscible evenly after, promptly carried out the censorship of leaching filtrate, can supply fill after qualified.

Four, post operation method

1, jacketed pan maneuver:

At first fasten the pot bottom dispensing valve before a, the use;

B, open a pot bottom interlayer exhaust steam valve;

C, slowly open the steam supply valve, observing exhaust pipe mouth has condensed water to flow out, and beginning of continuing has steam to discharge;

The steam discharge is as the criterion to having in a small amount for d, adjusting exhaust valve;

E, control steam supply valve size are observed ethanol volatilization situation in the pot, and switch steam supply valve control temperature is needless to say too high at any time;

F, constantly solution is measured temperature of liquid at any time and under alap temperature ethyl cellulose is all dissolved in the agitated kettle, but temperature be controlled at the highest must not be above 50 ℃.

Five, observation of curative effect: skin treatment film external classification and curative effect:

Clinical diagnosis	The example number	Curative effect						Total significant figure	Total effective rate %
										Produce effects	％	Effectively	％	Invalid	％
		Psoriasis	50	16	32	30	60									4	8	46	92
Neurodermatitis	5							2	40	2	40	1	20	4	80
		Chronic eczema	5	3	60	1	20									1	20	4	80
Meter	60							21	35	33	55	6	10	54	90

Six, toxic and side effects: observe 60 examples and do not find toxic and side effects.

Seven, drug evaluation:

This product is by form improvement, adds penetrating agent and filmogen, and external can form thin film, with isolate from outer air, can improve local curative effect, and it is convenient that patient uses heptan, and feel comfortable.It observes 60 examples to psoriasis, neurodermatitis, chronic eczema by clinical, and total effective rate is 90%, and psoriasis is observed 50 examples, and total effective rate is 92%, and wherein produce effects 16 examples account for 32%, and effective 30 examples account for 60%, and invalid 4 examples account for 8%; Neurodermatitis is observed 5 examples, and total effective rate is 80%, and wherein produce effects 2 examples account for 40%, and effective 2 examples account for 40%, and invalid 1 example accounts for 20%; Chronic eczema is observed 5 examples, total effective rate 80%.

Attached: model case:

1, name: Guo Zhiqing, the man, 50 years old, follow up a case by regular visits to patient card numbering 37, be diagnosed as psoriasis.This patient suffers from surplus the psoriasis 30 year, and whole body is covered with symmetric big or small speckle, and squama is arranged, there is abscess the part, sometimes play is itched, and winter-spring season is even more serious, with crossing mould, the Methoxypsoralen of winning honour for etc., psoriasis II number, medicines such as topsyne all do not have effect, use the compound phillyrin injection that certain curative effect is arranged, after stopping using, recurrence again.Current situation portion skin treatment film began to take effect after six-ten days, and the big portion of agents area speckle disappears, and squama reduces, and skin lesion reduces, and the Folium Styracis Suberifoliae rash has and disappears, and the pus rash goes down, and does not itch, and obviously takes effect.

2, name: Zhang Yusheng, man, 48 years old, follow up a case by regular visits to patient card numbering 21, be diagnosed as psoriasis, this patient suffers from surplus the psoriasis ten year, head, whole body are covered with symmetric speckle, and head has a large amount of squamas, and play is sometimes itched, used medicines such as Methoxypsoralen, topsyne in the past, all do not have effect, used the compound phillyrin injection, certain curative effect is arranged, after the drug withdrawal, recurrence.Now use the medicine-feeding of skin treatment film head instead, owing to be liquid, medicine-feeding is not evenly promptly itched after the patient comfort medication, big disappearance of squama, and the also big disappearance of speckle obviously takes effect.

Attached: psoriasis: diagnostic criteria:

1, be distributed in head, extremity stretch side, trunk, pimple that takes on a red color or speckle, upward the silvery white squama of multilamellar again has the thin film phenomenon, the petechial hemorrhage phenomenon, progressive stage returning property of isomorphic response.

2, usually the heavy summer in winter is light, and easily recurrence has gargalesthesia in various degree.

3, typical histo pathological change is arranged.

When 4, serious on skin lesion or non-skin lesion place syringe needle size abscess person occurs and be the abscess type; Irriate or deal with improperly and can develop into Folium Styracis Suberifoliae rash type; The symptoms of rheumatoid arthritis person of occurring together is an arthritis type.

Claims (2)

1. the preparation method of a coating agent of complex triamcinolone acetonide acetate, it is characterized in that adopting in the preparation process transdermal agent and film former to make compound liquid preparation, the volatilization naturally rapidly of the solvent part of compound liquid preparation, medicine then forms pharmaceutical film by means of film former on the surface; Its prescription and compound method are as follows:

Triamcinolone 69g ethyl cellulose 1.38kg

Lincomycin hydrochloride 841.5g acetone 10.89kg

Ether 9.85kg alcohol 58.58kg

Dimethyl sulfoxide 3.036kg Oleum Ricini 690ml

Total amount 100,000 ml.

2. according to the preparation method of the described coating agent of complex triamcinolone acetonide acetate of claim 1, it is characterized in that:

1) substrate liquid preparation: 95% ethanol that accurately takes by weighing institute's consumption 80%, drop in the jacketed pan standby, accurately weighing institute consumption ethyl cellulose is put in the enamel bucket, with part surplus ethanol, under constantly stirring, add in the cellulose, brute force stirs into pasty state, after all caking disappears, under agitation adds it in jacketed pan, then to the jacketed pan air feed, for guaranteeing to the greatest extent little volatile quantity, adopt interruptible gas supply in a small amount, stop heating during to 50 ℃ of temperature of liquid, constantly stir, till the fine plain off-bottom of second, the cooling of can in interlayer, washing by water, making a pot interior temperature of liquid reduce to 30 ℃ can use;

2) preparation of main liquid: accurately weighing triamcinolone, lincomycin hydrochloride, put and add dimethyl sulfoxide in the suitable molten device, in 70 ℃ of water-baths, heat, constantly stir, the control fluid temperature must not be higher than 50 ℃ to principal agent all till the dissolving;

3) close the liquid preparation: after treating that the cellulose solution temperature is reduced to 30 ℃, principal agent solution is under agitation added in the cellulose solution slowly, use the molten device of alcohol flushing of surplus then, again will

Acetone, ether add wherein slowly, after stirring makes mix homogeneously, do middle product chemical examination, qualified back fill with 100 order silk filtering and samplings.