CN1568943A

CN1568943A - Nitrol ointment, preparation method and application thereof

Info

Publication number: CN1568943A
Application number: CN 200410014738
Authority: CN
Inventors: 唐建华; 张银娣; 任宝华; 陆步实; 沈建平; 周立新; 邱俊; 吴建伟; 李丽敏; 潘国光
Original assignee: ZHEJIANG PINGHU SAPAS PHARMACEUTICAL CO Ltd; Jiangsu Provincial Institute of Materia Medica Co Ltd; Nanjing Medical University
Current assignee: ZHEJIANG PINGHU SAPAS PHARMACEUTICAL CO Ltd; Jiangsu Provincial Institute of Materia Medica Co Ltd; Nanjing Medical University
Priority date: 2004-04-26
Filing date: 2004-04-26
Publication date: 2005-01-26

Abstract

本发明公开了一种硝酸甘油软膏及其制备方法，该软膏由硝酸甘油、乳化剂、稀释剂和水组成，其制法是将乳化剂和稀释剂中的油相成分和水相成分分别混合后加热熔化，然后把油、水两相加热混合均匀，冷却后加硝酸甘油混合均匀制成。硝酸甘油软膏用于治疗男性勃起功能障碍、女性性功能低下和促进微血管扩张等，该软膏具有药物稳定性好，安全性强，制备工艺简便、生产成本低廉等优点。The invention discloses a nitroglycerin ointment and a preparation method thereof. The ointment is composed of nitroglycerin, an emulsifier, a diluent and water. The preparation method is to mix the oil phase components and the water phase components in the emulsifier and diluent respectively After heating and melting, the two phases of oil and water are heated and mixed evenly, and after cooling, nitroglycerin is added and mixed evenly. The nitroglycerin ointment is used for treating male erectile dysfunction, female sexual hypofunction and promoting capillary expansion, etc. The ointment has the advantages of good drug stability, strong safety, simple preparation process, low production cost and the like.

Description

Nitrol ointment and its production and application

One, technical field

The present invention relates to a kind of nitroglycerin external used medicine ointment, especially relate to a kind of sexual dysfunction that is used for the treatment of, promote Marjoram Extract, particularly treat nitroglycerin external used medicine ointment of erection disturbance and its production and application.

Two, background technology

Nitroglycerin is antianginal old medicine, and clinical practice has more than 100 year history, and it is rapid-action, weak point is kept in effect, nitrate esters smooth muscle cell can with the nitrate receptors bind, and by the sulfydryl of nitrate receptor be reduced into NO or-SNO (nitrous sulfydryl).In addition, the NO that disengages can also anticoagulant and adhesion, helps the treatment of coronary heart disease.

Along with to NO more and more deep understanding of the mechanism of action in circulation, immunity and nervous system, the application of NO and the treatment of NO related drugs more and more widely.Relation table between nitric oxide and the sexual function is present, and when a people was subjected to sexual stimulus, sexual organ's part can generate a large amount of nitric oxide, and intracellular cGMP is raise, and causes erection thus.

The progress and the clinical operating position of relevant nitroglycerin treatment erection disturbance are as follows both at home and abroad:

The foreign study situation

1.1989 year, Claes on the body of penis of 26 routine impotence patients, proved that nitroglycerin is effective to the patient of moderate erection disturbance with the patch of nitroglycerin or placebo.(Clacs?H.Transcutaneous?nitroglycerin?therapy?in?the?treatment?of?impotence.Urol?Int.1989；44(5)：309-12)

2.1989 year Owen etc. adopt the clinical experiment of placebo double blind control, treat 26 routine impotence patients with 2% nitrol ointment and write down the cavernous body of penis blood flow by tension pick-up record penis tension variation with ultrasonic figure, the result proves that nitrol ointment can increase the cavernous artery blood flow and penis is increased slightly. (Owen JA et al.Topical nitroglycerin:a potential treatment for impotence.J Urol.1989；143(3)：546-8)

3.1992 year foreign medical science urinary system fascicle report: 10 routine impotence patients, wherein sexual impotence is serious before the example treatment.10mg is applied on the penis with the nitroglycerin cream, and the result all obtains the effect of erecing, and wherein 4 routine patients finish sexual intercourse, and these patients used the papaverine injection in the past usually.

(Meyhoff HH. percutaneous nitroglycerin treatment sexual impotence [English] foreign medical science urinary system fascicle .1992; 6:280)

4. Britain Futura company develops this medicine cream in the nineties, and code name Med-900 contains nitroglycerin 2%, every pipe 2 grams.This medicine carries out clinical research in the U.S. and Korea S respectively, shows that through Korea S's 40 routine clinical researches patient's penis of 58% fully erects, and placebo only works to 10% patient.The effective percentage that fully erects and partly erect is 73%, placebo 18%.In the U.S. 60 routine patients are being lacked and carrying out this product erection function research under the condition of sexual stimulus, the result: 63% is effective, 13% produce effects; Usually onset in 5-20 minute, 45 minutes persistent period.Producing slight of short duration headache in this twice test is unique side reaction (1/4), but none is routine so and drug withdrawal does not have burning sensation and priapism to penis yet.Other has 100 examples to carry out in Birmingham queen Yi Lishabai hospital.Kemp thinks the existing enough data declaration OTC licences of the nitroglycerin cream of Futura, but this medicine still do not go public up till now, and reason is still indeterminate.(PJB?Publications?Ltd?Potential.new?impotence?drugcould?be?sold?OTC?SCRIP?NO2306?4?1998?P25)

U.S. International Medical Innovations, Inc. " contains water base external emulsifiable paste of nitroglycerin and its production and application " (the ZL patent No. 96192273.7) in the patent of invention of China's application, this external emulsifiable paste is by the nitroglycerin of 0.1-3 weight %, the penetration enhancer of 5-24 weight %, the water of 60-90 weight %, 0.5-3 the emulsifying agent of the thickening agent of weight % and 0.4-2 weight % is formed. show through our result of the test, wherein the water content of 60%-90% is enough to make the nitroglycerin hydrolysis, because nitroglycerin generally is kept in the dehydrated alcohol, so this external emulsifiable paste is unsettled, in addition, cream preparation method is comparatively complicated, and the adjuvant that adds is more, production cost is higher, simultaneously, also exists problems such as the not enough and safety of stability is not strong at the similar medicine of prior art.

Domestic research situation

1.1993 year the People's Hospital, Quanzhou City uses a nitroderm TTS and applies (nitroglycerin 25mg) in penis treatment sexual impotence 48 examples, produce effects 22 examples wherein, and 10 examples that take a turn for the better, total effective rate is 66%.The effective percentage of mental impoetence is 83%.Side effect: pulsatile headache appears in 4 routine patients in therapeutic process, removes that headache promptly disappears behind the medicine film, and 5 routine patients are sticking medicine film place skin rubefaction pruritus, and are unprocessed, die away after 1-2 hour. (Fujian medical magazine 1997; 19 (6) 85-6)

2.1994 year Huangpu, Shanghai City central hospital Andriatrics Dept. report: with nitroglycerin application treatment 3 routine impotence patients, result: hard erector's 13 examples are arranged. not hard erector's 10 examples., swell or react little weak person's 7 examples. and (spermology magazine 1994; 8 (3): 171-173)

3.1995 seeing, year Korea Spro knows report: 36 routine impotence patient age 22-86 year, June to 1 year at interval during sexual impotence, wherein 30 examples are used nitrol ointment 15mg, evenly be applied to penis dorsal part skin, found that penis length on average increases 1.65cm, the week footpath average 2.81cm (P＜0.01) of increasing .24 example is erected or part is erected, effective percentage is made color Doppler ultrasonography before and after reaching 80%. other 8 routine patient's coatings, dorsal artery of penis expands about 35.72% after finding coating, the Sponge expansion is more than 50%, and significantly increase its blood flow rate and blood flow, after its mechanism possibility nitroglycerin is applied to skin outward, can quickens Transdermal absorption, and stagnate in the Sponge tissue, the guanosine circulation is increased, the N0 level improves, and causes the Sponge smooth muscle loosening, and blood flow volume increases, be full of sinusoid, thereby bring out erection. (clinical magazine of urology surgery 1995; 10 (4): 239; 241 Guangdong pharmacy 1999; 9 (1): 12-12)

4.1999 10 routine impotence patients are treated with the nitroglycerin cream by year Zhongshan Medical Univ. and Huaxi Medical Univ, its 7 example is kept 10-30 minute erection time, 2 examples are fully erected, 6 example 5-10 minute erection times of reaction. and (the Chinese Pharmaceutical Association scientific paper collection first volume in 1999 is P.158)

Three, summary of the invention

1. goal of the invention

The object of the present invention is to provide a kind of good stability, high safety, technology preparation easy, with low cost to treat external nitrol ointment of erection disturbance and preparation method thereof.

2. technical scheme

(1) a kind of nitrol ointment, its component and percetage by weight content are: nitroglycerin 0.5-3.0%, emulsifying agent 5.0-20%, diluent 40-79%, water 15-50%.

The preferred content of above-mentioned nitroglycerin is: 2.0%.

Above-mentioned emulsifying agent is: Polyethylene Glycol-7 stearate and analog thereof are as (HLB value 4-12) such as Polyethylene Glycol-75 glyceryl stearate, Polyethylene Glycol-32 stearate, Polyethylene Glycol-8 Cera Flava ester, polyglycereol-3 distearates; Tween (comprising tween 80,20,40,65, HLB value 10-20 such as 85); Span (comprising Arlacel-20,40,60, HLB value 4-12 such as 85).

Above-mentioned diluent is: stearic acid (octadecanoid acid) and derivant thereof (contain C _18-54), the derivant of stearyl alcohol (octadecanol) and aliphatic alcohol thereof (contains C _18-36), vaseline (white vaseline, Yellow Vaselin), lanoline, liquid Paraffin (lightweight, heavy), glycerol (glycerol), propylene glycol etc.

A kind of preparation method of nitrol ointment, its step of preparation process is as follows:

(1), after promptly stearic acid 6-12g, stearyl alcohol 4-10g, vaseline 3-6g, liquid Paraffin 2-15g mix, heats 40-80 ℃ and dissolve at first with oil phase substance;

(2), after promptly glycerol 30-40g, Polyethylene Glycol-7 stearate 4-7g, tween 80 4.4-6g, water 24-33 g mix, heat 40-80 ℃ and dissolve secondly with aqueous phase substance.

(3) then with oil, the biphase material of water at 50-80 ℃ of following mix homogeneously, be cooled to room temperature after, add nitroglycerin 0.5-3g mix homogeneously and promptly get ointment.

Except that above-mentioned step of preparation process, also comprise other preparation methoies commonly used on the pharmaceutics.

The application of nitrol ointment in the medicine of preparation treatment male erectile dysfunction.

The application of nitrol ointment in the low medicine of preparation treatment femal sexual function.

The application of nitrol ointment in the medicine of preparation promotion Marjoram Extract.

3. beneficial effect

Nitrol ointment of the present invention compared with prior art has following characteristics:

(1) stability is better.Nitroglycerin is met the water facile hydrolysis, therefore the content for preparing water in the component of ointment is too many, cause the hydrolysis of nitroglycerin easily, make the medicine instability, we at first select an amount of water content for this reason, thereby make the stability of ointment medicament better, simultaneously, we keep sample for a long time with nitrol ointment of the present invention and imitative patent ZL96192273.7 nitroglycerin emulsifiable paste and test and accelerated test.Result of the test sees Table 1,2.Result of the test as can be seen, our developed product is investigated keeping sample for a long time, 2 years still stable, appearance character is even, content does not have significant change, does not have lamination yet, though related substance increases to some extent, but still at acceptability limit, accelerated test also shows equally to be stablized; Keeping sample for a long time of proprietary articles investigated and accelerated test is all defective and copy, and sees Table 3,4, and especially the character variation is comparatively outstanding, becomes brown paste and layering from white paste, and content descends obviously, and related substance obviously increases.This shows that the stability of nitrol ointment of the present invention obviously is better than imitative proprietary articles nitroglycerin emulsifiable paste.

(2) safe and effective.Prove that from the result of pharmacological toxicology test this nitrol ointment has the effect of obvious enhancing erection function, and through the evidence of animal zest and anaphylactic reaction: behind complete sum damaged skin of 2% nitrol ointment partial smearing rat or the penis of Cavia porcellus congested phenomenon is arranged, but do not see that the part has erythema or edema to form, show no obvious local irritation reaction and anaphylaxis.

(3) production technology is easy, has reduced production cost, helps industrial large-scale production.

The nitrol ointment test (developed product) that keeps sample for a long time

Get three batches of this product, press commercially available back, place under 25 ℃ ± 2 ℃, relative humidity 60% ± 10%, accelerated test result's (40 ℃, relative humidity 75%) condition and place, and, the results are shown in Table 1,2 in 12,24 months sample analysis.

Table 1 result of the test (25 ℃ ± 2 ℃, relative humidity 60% ± 10%) that keeps sample for a long time

Lot number time (moon) character uniformity content (%) related substance has or not layering

0 simple ointment uniform and smooth 98.01 does not detect not layering

020,206 12 simple ointment uniform and smooth 98.26 do not detect not layering

24 simple ointment uniform and smooth 97.34 are less than 5% not layering

0 simple ointment uniform and smooth 98.81 does not detect not layering

020,207 12 simple ointment uniform and smooth 96.75 are less than 5% not layering

24 simple ointment uniform and smooth 97.56 do not detect not layering

0 simple ointment uniform and smooth 99.70 does not detect not layering

020,208 12 simple ointment uniform and smooth 99.17 do not detect not layering

24 simple ointment uniform and smooth 95.24 are less than 5% not layering

Table 2 accelerated test result (40 ℃, relative humidity 75%)

Lot number time (moon) character uniformity content (%) related substance has or not

Layering

0 simple ointment uniform and smooth 98.01 does not detect not layering

1 simple ointment uniform and smooth 98.99 does not detect not layering

020,206 2 simple ointment uniform and smooth 98.33 do not detect not layering

3 not layerings of simple ointment uniform and smooth 101.2＜1%

6 not layerings of faint yellow ointment uniform and smooth 104.5＜2%

0 simple ointment uniform and smooth 98.81 does not detect not layering

1 simple ointment uniform and smooth 98.72 does not detect not layering

020,207 2 simple ointment uniform and smooth 98.32 do not detect not layering

3 not layerings of simple ointment uniform and smooth 101.2＜1%

6 not layerings of faint yellow ointment uniform and smooth 103.2＜2%

0 simple ointment uniform and smooth 99.70 does not detect not layering

1 simple ointment uniform and smooth 99.40 does not detect not layering

020,208 2 simple ointment uniform and smooth 98.46 do not detect not layering

3 not layerings of simple ointment uniform and smooth 100.1＜1%

6 not layerings of faint yellow ointment uniform and smooth 104.4＜2%

The test (imitative proprietary articles ZL 96192273.7) that keeps sample for a long time of nitroglycerin emulsifiable paste

Table 3 result of the test that keeps sample for a long time

0 white paste uniform and smooth 102.34 does not detect not layering

Inhomogeneous 93.54＞7% not layerings of 020,206 6 light yellow pastes

Inhomogeneous 57.4＞10% layerings of 12 brown pastes

0 white paste uniform and smooth 101.3 does not detect not layering

Inhomogeneous 88.97＞7% not layerings of 020,207 6 light yellow pastes

Inhomogeneous 55.26＞10% layerings of 12 brown pastes

0 white paste uniform and smooth 98.45 does not detect not layering

Inhomogeneous 89.76＞7% not layerings of 020,208 6 light yellow pastes

Inhomogeneous 56.67＞10% layerings of 12 brown pastes

Table 4, accelerated test result's (40 ℃, relative humidity 75%)

Layering

0 white paste uniform and smooth 102.34 does not detect not layering

Inhomogeneous 70.87＞10% layerings of 1 light yellow paste

Inhomogeneous 50.89＞10% layerings of 020,206 2 brown pastes

Inhomogeneous 20.67＞10% layerings of 3 brown pastes

Inhomogeneous 21.8＞10% layerings of 6 brown pastes

0 white paste uniform and smooth 101.3 does not detect not layering

Inhomogeneous 80.45＞10% layerings of 1 light yellow paste

Inhomogeneous 54.55＞10% layerings of 020,207 2 brown pastes

Inhomogeneous 23.87＞10% layerings of 3 brown pastes

Inhomogeneous 24.32＞10% layerings of 6 brown pastes

0 simple ointment uniform and smooth 98.45 does not detect not layering

Inhomogeneous 73.46＞10% layerings of 1 light yellow paste

Inhomogeneous 56.67＞10% layerings of 020,208 2 brown pastes

Inhomogeneous 23.34＞10% layerings of 3 brown pastes

Inhomogeneous 22.28＞10% layerings of 6 brown pastes

Four, the specific embodiment:

(1) embodiment of the component of nitrol ointment and weight proportion:

Example 1, nitroglycerin 2g

Stearic acid 6g

Stearyl alcohol 6g

White vaseline 6g

Liquid Paraffin 8.4g

Polyethylene Glycol-7 stearate 4g

Tween 80 4.4g

Glycerol 30g

Water adds to 100g

Example 2,

Nitroglycerin 0.5g

Stearic acid 8g

Stearyl alcohol 4g

Yellow Vaselin 4g

Liquid Paraffin 15g

Polyethylene Glycol-75 glyceryl stearate 4g

Tween 80 6g

Glycerol 40g

Water adds to 100g

Example 3,

Nitroglycerin 1g

Stearic acid 10g

Stearyl alcohol 10g

Lanoline 3g

Liquid Paraffin 5g

Polyethylene Glycol-8 Cera Flava ester 5g

Tween-65 10g

Glycerol 33g

Water adds to 100g

Example 4,

Nitroglycerin 3g

Stearic acid 7g

Hexadecanol 8g

White vaseline 4g

Liquid Paraffin 15g

Polyethylene Glycol-32 stearate 7g

Tween 85 6g

Propylene glycol 25g

Water adds to 100g

Example 5,

Nitroglycerin 2g

Stearic acid 12g

Stearyl alcohol 10g

White vaseline 3g

(heavy) liquid Paraffin 2g

Polyglycereol-3 distearate 14g

Arlacel-60 6g

Glycerol 40g

Water adds to 100g

Example 6,

Nitroglycerin 2g

Calcium stearate 6g

Stearyl alcohol 6g

White vaseline 6g

Light liquid petrolatum 8g

Polyethylene Glycol-7 stearate 4g

Tween 80 5g

Glycerol 30g

Water adds to 100g

(2) embodiment of nitrol ointment preparation method:

A kind of preparation method of stable nitrol ointment, its step of preparation process is as follows:

(1), after oil phase (stearic acid 8g, stearyl alcohol 4g, vaseline 6g, liquid Paraffin 8g) mixes, heats 40-80 ℃ and dissolve;

(2), after water (glycerol 30g, Polyethylene Glycol-7 stearate 6g, tween 80 6g, water 30g) mixes, heat 40-80 ℃ and dissolve;

(3), above-mentioned oil, water is biphase at 50-80 ℃ of mix homogeneously, be cooled to room temperature after, add nitroglycerin 2g, mix homogeneously is made.

(3) nitrol ointment pharmacology, toxicity, the embodiment of Transdermal absorption test:

The local pharmacodynamics that uses the sexual function improving effect of example 1 nitrol ointment

This experiment is observed the local influence of using sexual function of rats of nitrol ointment by three aspects:

1. 1%, 2% nitrol ointment can obviously shorten castration male rat erection incubation period; And the incubation period that the normal male rat is pounced on catch female Mus shorten, pounce on and catch number of times and increase.Point out this portion of officina to use and to improve the irritability of rat, the effect of sexual function improving is arranged erecing.

2. observe with MCIP Microcirculatory Image processing system and measure in real time and the main blood capillary caliber in the statistics penis back side is measured before and after administration rate of change.The result: 0.5% nitrol ointment, though 15min can make the penis Marjoram Extract, effect rapidly disappears.1% and 2% nitrol ointment can make the penis blood capillary obviously expand after smearing 15min, and the effect peak period can be maintained until 30min, and effect later on weakens gradually, but 60min still has tangible dilating effect after the administration.Nitrol ointment has expands the effect of rat penis blood capillary preferably.

3. place the rat radix penis part with miniature laser doppler probe, and lead the pharmacology signal processing system more and be connected, operation computer dedicated program is sampled and graphic recording, observes blood flow curve before and after the administration.The result: 0.5% nitrol ointment is smeared the visible rat arteria penis blood flow in back to be increased, and does not change but reach significance as yet; 1% and 2% concentration nitrol ointment can cause that after administration the arteria penis blood flow increases in 5 minutes, and effect in 30 minutes begins to disappear after the administration.2% mass action is the strongest, and is lasting relatively.This preparation of the local use of above presentation of results penis has obvious expansion arteria penis, improves regional flow's effect.

4. 8 beasle dogs (10kg) are under pentobarbital anesthesia, and 1% or 2% concentration nitrol ointment partial smearing 5mg or 10mg can make the dog penis increase, and Zhou Jing increases slightly.

The local toxicology of using of example 2 nitrol ointments

1. 20% nitrol ointment (1g) is not seen obvious adverse reaction through the rat one or many to intact skin or damaged skin toxicity test.Result: maximum tolerated dose＞200mg/200g.20% nitrol ointment is through rat damaged skin test, and the gruel of withering of rat outward appearance after administration has hard hair phenomenon, rises in the 3rd～4 day to begin to recover normal, and the damaged skin healing is good, and animal does not have death.Result: maximum tolerated dose＞200mg/200g.2% nitrol ointment (1g) is no matter at the Cavia porcellus penis and on every side or after vagina and the one or many coating on every side thereof, as seen penis is congested erects, the hyperemia of vaginal orifice wall thickens, along with the free movable back of Cavia porcellus disappears. the repeatedly no abnormal discovery of pathological examination results after the coating.

2. 2% nitrol ointment guinea pig back one or many is after complete or damaged skin are smeared, and visible skin has congested phenomenon, goes the ointment base reaction of nitroglycerin not obvious.Damaged skin is healing voluntarily in 2-3 days.The damaged skin tissue slice is checked, no abnormal discovery.Repeatedly apply the no abnormal discovery of pathological examination results behind the damaged skin.

3. the skin after 2% nitrol ointment partial smearing every day has congested phenomenon, does not see that the part has erythema or edema to form.Positive sensitizer Cavia porcellus group last sensitization is removed and is tried 24h behind the thing, sensitization rate 100%, and the reaction meansigma methods is 2.5; 48h afterreaction meansigma methods is 1.2; Behind the 72h for 1.0.2% nitrol ointment group and matrix group last sensitization remove tried thing after 24h respectively have two routine dermathemia similar with erythema, promptly disappear behind the 48h.

From the above-mentioned several animal models explanation nitrol ointment local application that provides the curative effect that strengthens erection function is arranged.Its therapeutic dose and toxic dosage differ greatly, and zest and anaphylaxis are also lower, and therefore the part has use value with nitrol ointment.

Example 3 nitrol ointments are to the penis Transdermal absorption test of beasle dog

Article 8, beasle dog intersects penis and smears and contain not commensurability nitroglycerin (5mg, nitrol ointment 10mg/35h) and intravenous drip nitroglycerin (0.125mg/kg/10min) be self reference, with gas phase electron capture method method mensuration drug-time curve.Result of the test: local penis coating 1% and 2%0.5g nitrol ointment, its main pharmacokinetic parameter: Cmax (μ gL ^-1): 0.97 ± 0.33 and 1.67 ± 0.61; Tmax (h): 6.4 ± 3.5 and 8.1 ± 4.4; AUC _0-35(μ ghL ^-1): 14.90 ± 4.78 and 22.97 ± 5.14.The nitroglycerin that 5mg and 10mg/35h discharge with respect to the trap (F%) of intravenous drip 1.25mg/10min is: 178 ± 114% and 172 ± 75%. explanations:

1. the individual absorption difference of local penis coating is bigger;

2. local coating 5mg, the absorption of 10mg nitroglycerin in 35 hours is equivalent to the absorbtivity of 4 or 8 times of intravenous drip 1.25mg/10min approximately.

3. nitroglycerin intravenous drip, local coating 5mg, the Cmax of 10mg is respectively: 11.94 ± 7.30,0.97 ± 0.33 and 1.67 ± 0.61,

Show: local penis is smeared the nitroglycerin 5mg in the nitrol ointment, can be absorbed rapidly behind the 10mg, and its Cmax (ng/ml) is between 0.63-3.05.

Claims

1. a kind of nitroglycerin ointment, its component and weight percent content are:

(1) Nitroglycerin 0.5-3%.

(2) Emulsifier: 5-20%.

(3) Thinner: 40-79%.

(4) Water: 15-50%.

2. nitroglycerin ointment according to claim 1 is characterized in that described emulsifier is: macrogol-7 stearate and analog thereof, Tween, Span.

3. nitroglycerin ointment according to claim 2, is characterized in that described analog is macrogol-75 glyceryl stearate, macrogol-32 stearate, macrogol- 8 beeswax esters, polyglycerol-3 distearate, its HLB value 4-12; described Tween includes Tween-80, 20, 40, 65, 85, its HLB value 10-20; Span includes Span-20, 40, 60, 85, and its HLB value is 4-12.

4. nitroglycerin ointment according to claim 1 is characterized in that described diluent is: stearic acid and derivatives thereof, stearyl alcohol and fatty alcohol derivatives thereof, petrolatum, lanolin, liquid paraffin, Glycerin, Propylene Glycol

5. The nitroglycerin ointment according to claim 4, characterized in that the stearic acid derivative contains C _18-54 ; the fatty alcohol derivative contains C _18-36 .

6. a method for preparing claim 1 nitroglycerin ointment, its preparation process step is:

(1) First, mix the oil phase substances, namely 6-12g of stearic acid, 4-10g of stearyl alcohol, 3-6g of vaseline, and 2-15g of liquid paraffin, and heat to 40-80°C to dissolve;

(2) Next, after mixing the water phase substance, namely 30-40g of glycerin, 4-7g of polyethylene glycol-7 stearate, 4.4-6g of Tween-80, and 24-33g of water, heat to 40-80°C to dissolve;

(3) Then, the above-mentioned oil and water two-phase substances are mixed uniformly at 50-80° C., cooled to room temperature, and 0.5-3 g of nitroglycerin is added and mixed uniformly to prepare.

7. Application of nitroglycerin ointment in the preparation of medicine for treating male erectile dysfunction.

8. Application of nitroglycerin ointment in the preparation of medicine for treating female sexual hypofunction.

9. Application of nitroglycerin ointment in the preparation of drugs for promoting microvascular expansion.