CN102018660A - Naftopidil suppository and preparation method thereof - Google Patents

Abstract

The invention relates to naftopidil suppository and a preparation method thereof. The naftopidil suppository comprises the following components in part by weight: 10 to 25 parts of naftopidil, 10 to 60 parts of oleaginous substrate, 10 to 60 parts of water-soluble substrate, 1 to 10 parts of surfactant, 10 to 30 parts of hardening agent and 5 to 15 parts of absorbefacient. The suppository is uniformly dispersed, has high dissolution rate and improves the bioavailability and the effectiveness of medicaments.

Description

Naftopidil suppository and preparation method thereof

Technical field

The present invention relates to field of pharmaceutical preparations, particularly relate to a kind of naftopidil suppository and preparation method thereof.

Background technology

Naftopidil is a1 receptor antagonist optionally, can be used for alleviating the prostate due to this receptor excitement and the sympathetic nerve sexual tension of urethra by the a1 receptor blocking, it is intrinsic pressure to reduce urethra, improve the symptoms such as dysuria due to the benign prostate hyperplasia, can also suppress the increased blood pressure that the a1 receptor causes, and have calcium antagonism concurrently, multiple hypertension animal model there is hypotensive effect.It is applicable to the patient of hypertension companion hyperlipemia, diabetes, prostatic hyperplasia.

Existing market naftopidil solid preparation has tablet, capsule, drop, and these all are oral formulations, and are all lower at dissolution in vitro, and blood drug level and bioavailability are also lower; Naftopidil has local irritation, it is more obvious when concentration is higher, common oral preparation oral be quick disintegrate, local concentration is higher and produce gastrointestinal is stimulated, can cause stomach discomfort or feel sick, edema, shiver, AST raises and untoward reaction such as ALT rising, and liver is also had certain toxicity.In addition naftopidil is produced the therapeutical effect that common preparation can not be given full play to this medicine, for the patient, with other medicine with there is no tangible advantage with this medicine.

Summary of the invention

The purpose of this invention is to provide the suppository that is used for cavity/canal drug administration that naftopidil and suitable substrate are made, to overcome the above-mentioned defective that prior art exists.

The invention provides a kind of naftopidil suppository, it comprises following component by weight:

10～25 parts of naftopidils

10～60 parts of greasing bases

10～60 parts of water-soluble basees

1～10 part in surfactant

10～30 parts of sclerosing agents

5～15 parts of absorption enhancers.

Preferably, it comprises following component by weight:

20 parts of naftopidils

35 parts of greasing bases

25 parts of water-soluble basees

5 parts in surfactant

10 parts of sclerosing agents

5 parts of absorption enhancers.

Wherein, described greasing base is selected from one or more in cocos nucifera oil ester, shancangzi oil ester, cetylate, stearic acid and the propylene glycol ester.

Described water-soluble base is selected from one or more in glycerol, gelatin and the Polyethylene Glycol.

Described surfactant is selected from one or more in polyoxyethylene, single-hard ester acid ester class and the poloxamer.

Described sclerosing agent is selected from one or more in white beeswax, stearic acid and the Brazil wax.

Described absorption enhancer is selected from one or more in fatty acid, aliphatic alcohol, uric acid, sodium salicylate, sodium benzoate and the cyclodextrin.

The present invention also provides the method for the above-mentioned naftopidil suppository of preparation, comprises the steps:

1) naftopidil and greasing base are crossed 100～120 mesh sieves are pulverized and mix homogeneously is standby;

2) with water-soluble base 60-90 ℃ of water-bath fusion;

3) with 1) the gained mixture adds 2) stir in the fused mass of gained and make its fusing;

4) surfactant, sclerosing agent, absorption enhancer are added 3) in stir, make the paste charges of suppository;

5) etc. 4) temperature of prepared paste charges drops to below 40 ℃, is poured in the mould, through cooling, after the curing, removes the part of overflowing, and opens the bolt mould, releases.

Naftopidil suppository of the present invention has following beneficial effect;

1) naftopidil be water insoluble and fusing point high, so in prescription, select greasing base and absorption enhancer to make paste.

2) under the dry storage condition, have fusing point, when transportation or lay up period variations in temperature, can keep stable and not melt than fever; Because the humidity of intracavity moisturizes suppository and its fusing point is reduced, medicine can effectively discharge in body cavity when inserting rectum.

3) naftopidil suppository makes medicine not be subjected to the destruction of gastrointestinal pH or enzyme, medicine absorbs from rectum, the destruction that is subjected to the liver first-pass effect in the time of can avoiding oral, suppository in vivo can biodegradation, noresidue and toxic and side effects, can also reduce toxicity and the side effect of medicine, the safety that has improved medicine to liver.

4) medicine directly disturbs from rectum absorptance oral absorption and lacks, and the action time of suppository is longer than general oral tablet, is a kind of effective route of administration to the patient with vomiting.

5) dispersion of medicine, dissolution rate is stable; Improved the effectiveness of bioavailability and medicine.

The specific embodiment

Following examples are used to illustrate the present invention, but are not used for limiting the scope of the invention.

Embodiment 1

Take by weighing raw material by following proportioning:

Naftopidil: 400g

Stearic acid: 700g (Hunan Er-kang Pharmaceutical Co., Ltd., down together)

Cetomacrogol 1000: 200g (Hunan Er-kang Pharmaceutical Co., Ltd., down together)

Macrogol 4000: 300g (Hunan Er-kang Pharmaceutical Co., Ltd., down together)

Poloxamer (40): 100g (Hunan Er-kang Pharmaceutical Co., Ltd., down together)

White beeswax: 200g (Hunan Er-kang Pharmaceutical Co., Ltd., down together)

Sodium benzoate: 100g (Hunan Er-kang Pharmaceutical Co., Ltd., down together)

Make 1000

Preparation method is as follows:

1) naftopidil and stearic acid are crossed 120 mesh sieves are pulverized and mix homogeneously is standby;

2) under 80 ℃ of water-baths with cetomacrogol 1000 and Macrogol 4000 fusion;

3) with 1) add 2) in stir and make its fusing;

4) with poloxamer (40), white beeswax, sodium benzoate adds 3) in stir, make the paste charges of suppository;

5) etc. 4) temperature of prepared paste charges drops to below 40 ℃, is poured in the mould, through cooling, after the curing, removes the part of overflowing, and opens the bolt mould, releases.

Embodiment 2

Take by weighing raw material by following proportioning:

Naftopidil: 300g

Stearic acid: 600g

Cetomacrogol 1000: 300g

Macrogol 4000: 300g

Poloxamer: 200g

White beeswax: 200g

Sodium benzoate: 100g.

Preparation method is as follows:

1) naftopidil and stearic acid are crossed 100 mesh sieves are pulverized and mix homogeneously is standby;

2) under 60 ℃ of water-baths with cetomacrogol 1000 and Macrogol 4000 fusion;

3) with 1) add 2) in stir and make its fusing;

4) with poloxamer (40), white beeswax, sodium benzoate adds 3) in stir, make the paste charges of suppository;

5) etc. 4) temperature of prepared paste charges drops to below 40 ℃, is poured in the mould, through cooling, after the curing, removes the part of overflowing, and opens the bolt mould, releases.

Embodiment 3

Take by weighing raw material by following proportioning:

Naftopidil: 400g

Stearic acid: 700g

Cetomacrogol 1000: 200g

Polyethylene glycol 6000: 300g (Hunan Er-kang Pharmaceutical Co., Ltd., down together)

Poloxamer: 100g

White beeswax: 200g

Sodium benzoate: 100g.

Preparation method is as follows:

1) naftopidil and stearic acid are crossed 110 mesh sieves are pulverized and mix homogeneously is standby;

2) under 80 ℃ of water-baths with cetomacrogol 1000 and polyethylene glycol 6000 fusion;

3) with 1) add 2) in stir and make its fusing;

4) with poloxamer (40), white beeswax, sodium benzoate adds 3) in stir, make the paste charges of suppository;

5) etc. 4) temperature of prepared paste charges drops to below 40 ℃, is poured in the mould, through cooling, after the curing, removes the part of overflowing, and opens the bolt mould, releases.

Embodiment 4

Take by weighing raw material by following proportioning:

Naftopidil: 400g

Stearic acid: 600g

Cetomacrogol 1000: 300g

Macrogol 4000: 300g

Poloxamer: 150g

White beeswax: 100g

Sodium salicylate: 150g.

Preparation method is as follows:

1) naftopidil and stearic acid are crossed 120 mesh sieves are pulverized and mix homogeneously is standby;

2) under 80 ℃ of water-baths with cetomacrogol 1000 and Macrogol 4000 fusion;

3) with 1) add 2) in stir and make its fusing;

4) with poloxamer (40), white beeswax, sodium benzoate adds 3) in stir, make the paste charges of suppository;

5) etc. 4) temperature of prepared paste charges drops to below 40 ℃, is poured in the mould, through cooling, after the curing, removes the part of overflowing, and opens the bolt mould, releases.

Embodiment 5

Take by weighing raw material by following proportioning:

Naftopidil: 500g

Cocos nucifera oil ester: 100g

Cetylate: 100g

Cetomacrogol 1000: 800g

Glycerol: 400g

Polyoxyethylene: 10g

Single-hard ester acid ester: 10g

White beeswax: 300g

Brazil wax: 300g

Aliphatic alcohol: 60g

Uric acid: 20g

Cyclodextrin: 20g.

Preparation method is as follows:

1) also mix homogeneously is standby naftopidil, cocos nucifera oil ester and cetylate to be crossed the pulverizing of 120 mesh sieves;

2) under 80 ℃ of water-baths with cetomacrogol 1000 and glycerol fusion;

3) with 1) add 2) in stir and make its fusing;

4) polyoxyethylene, single-hard ester acid ester, white beeswax, Brazil wax, aliphatic alcohol, uric acid and cyclodextrin are added 3) in stir, make the paste charges of suppository;

5) etc. 4) temperature of prepared paste charges drops to below 40 ℃, is poured in the mould, through cooling, after the curing, removes the part of overflowing, and opens the bolt mould, releases.

Experimental example

Table 1 dissolution test

Sample time (min)	15	30	45	60	120	240
							The naftopidil sheet	7.66	24.78	41.54	55.43	70.32	78.36
The naftopidil capsule	4.58	25.13	44.15	60.47	72.21	80.11
							Embodiment 1	9.59	33.98	52.32	75.05	87.96	95.44
Embodiment 2	8.01	24.11	39.43	75.13	78.32	91.51
							Embodiment 3	7.95	23.19	40.23	69.78	81.02	92.36
Embodiment 4	10.1	35.95	56.23	80.1	93.4	95.87
							Embodiment 5	10.3	34.75	58.33	79.8	91.7	94.95

The result shows: test data sees that naftopidil suppository stripping situation is better than tablet, capsule, and dissolution rate is more complete.

2) absorption test in the body: in the hyperplasia of prostate patient treatment, divide naftopidil suppository treatment group (1 group of the suppository corresponding A that makes with embodiment 1 at random; 2 groups of the suppository corresponding A that makes with embodiment 2; 3 groups of the suppository corresponding A that makes with embodiment 3; 4 groups of the suppository corresponding A that makes with embodiment 4,5 groups of the suppository corresponding A that makes with embodiment 5) and naftopidil tablet in treatment group (B group), the result shows that medication one all A1, A4 and A5 group patient are clearly better 94%; A2 and A3 group patient are clearly better 90%; B group patient is clearly better 72%, and final cure rate A1, A4 and A5 group are 95%; The A2 group is 90%; The A3 group is 93%, and the B group is 82%.

Claims (8)

1. a naftopidil suppository is characterized in that, comprises following component by weight:

10～25 parts of naftopidils

10～60 parts of greasing bases

10～60 parts of water-soluble basees

1～10 part in surfactant

10～30 parts of sclerosing agents

5～15 parts of absorption enhancers.

2. naftopidil suppository according to claim 1 is characterized in that, comprises following component by weight:

20 parts of naftopidils

35 parts of greasing bases

25 parts of water-soluble basees

5 parts in surfactant

10 parts of sclerosing agents

5 parts of absorption enhancers.

3. naftopidil suppository according to claim 1 and 2 is characterized in that, described greasing base is selected from one or more in cocos nucifera oil ester, shancangzi oil ester, cetylate, stearic acid and the propylene glycol ester.

4. naftopidil suppository according to claim 1 and 2 is characterized in that described water-soluble base is selected from one or more in glycerol, gelatin and the Polyethylene Glycol.

5. naftopidil suppository according to claim 1 and 2 is characterized in that described surfactant is selected from one or more in polyoxyethylene, single-hard ester acid ester class and the poloxamer.

6. naftopidil suppository according to claim 1 and 2 is characterized in that described sclerosing agent is selected from one or more in white beeswax, stearic acid and the Brazil wax.

7. naftopidil suppository according to claim 1 and 2 is characterized in that described absorption enhancer is selected from one or more in fatty acid, aliphatic alcohol, uric acid, sodium salicylate, sodium benzoate and the cyclodextrin.

8. prepare the method for claim 1 or 2 described naftopidil suppositorys, comprise the steps:

1) naftopidil and greasing base are crossed 100～120 mesh sieves are pulverized and mix homogeneously is standby;

2) with water-soluble base 60-90 ℃ of water-bath fusion;

3) with 1) the gained mixture adds 2) stir in the fused mass of gained and make its fusing;

4) surfactant, sclerosing agent, absorption enhancer are added 3) in stir, make the paste charges of suppository;

5) etc. 4) temperature of prepared paste charges drops to below 40 ℃, is poured in the mould, through cooling, after the curing, removes the part of overflowing, and opens the bolt mould, releases.