CN1274581A - Application of Alpha-adrenaline receptor blocking agent in preparing medicine for man's sexual dysfunction - Google Patents
Application of Alpha-adrenaline receptor blocking agent in preparing medicine for man's sexual dysfunction Download PDFInfo
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- CN1274581A CN1274581A CN 99107479 CN99107479A CN1274581A CN 1274581 A CN1274581 A CN 1274581A CN 99107479 CN99107479 CN 99107479 CN 99107479 A CN99107479 A CN 99107479A CN 1274581 A CN1274581 A CN 1274581A
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Abstract
The Alpha-Adrenaline receptor blocking agent is Phentolaminum, Tolazoline, Phenoxybenzamine or their medicinal acceptable salt. The medicine of the present invention has small dosage, fast effect and less toxic side effect.
Description
The present invention relates to the application of alpha-2-adrenoceptor blocker in the medicine of preparation treatment male sexual disorder, more specifically relate to the application of acceptable salt on phentolamine, tolazoline, phenoxybenzamine or its materia medica.
According to documents and materials, there is impotence patient about 3,000 ten thousand, Canadian about 3,000,000 in the U.S..The male in Taiwan is because the medea of must nourishing is eaten up about 2,500,000,000 Hongkong dollars every year.Domestic in China, along with the raising of living standards of the people, also more and more urgent to the improvement of life quality.This shows that human demand to treatment male erectile disorder medicine is very huge.In recent years, the medicine " viagra (Viagro) " of the treatment male sexual disorder of Pfizer drugmaker development is fashionable for a time in the world, obtains immense success, and this point also just is being described.
Therefore, the medicine that the purpose of this invention is to provide the little treatment male sexual disorder of a kind of effect height, side effect.
According to the present invention, it provides the application of alpha-2-adrenoceptor blocker in the medicine of preparation treatment male sexual disorder, and wherein said alpha-2-adrenoceptor blocker is an acceptable salt on phentolamine, tolazoline, phenoxybenzamine or its materia medica.
Known alpha-2-adrenoceptor blocker as phentolamine, tolazoline, phenoxybenzamine, mainly is the hypertensive episode that is used for the treatment of due to the pheochromocytoma; The treatment left heart failure; And the cutaneous necrosis of treatment norepinephrine administration due to excessive.
The mechanism of above-mentioned therapeutical effect is respectively:
Hypertensive episode due to the treatment pheochromocytoma: when suffering from pheochromocytoma (being adrenal gland's body tumor), a large amount of secretion epinephrines, make hypertension, said medicine can optionally be blocked alpha-2-adrenoceptor, makes adrenergic boosting upset be hypotensive effect.
The treatment left heart failure: small artery and venular reflexive are shunk in the time of can removing heart failure owing to said medicine, reduce Peripheral resistance, and cardiac afterload is reduced, and output increases, thereby heart failure is improved.
Cutaneous necrosis due to the administration of treatment norepinephrine is excessive: said medicine can be removed the small artery in the cutaneous necrosis zone, venular reflexive is shunk, make its diastole, local blood circulation is improved, and blood prevents dermonecrotic further developing for recovering.
In the research process to said medicine, inventor of the present invention finds that acceptable salt on alpha-2-adrenoceptor blocker, especially phentolamine, tolazoline, phenoxybenzamine and the materia medica thereof can optionally be blocked postsynaptic α
1-adrenoreceptor is characterized in stronger to vein and venule effect, and it is open to make blood vessel expand about flesh, increases the parasympathetic tension force of periphery, reduces orthosympathetic tension force.The erection of penis then is subjected to parasympathetic stimulation, when the parasympathetic nervous excitation time, and genitals's vasodilation that it is arranged.Therefore, said medicine increases the cavernous body of penis vascular flow by expansion genitals blood vessel, impels the congested erection of penis, reaches the purpose of side chain male sexual disorder.In said medicine, phentolamine most preferably.
Acceptable salt comprises the salt that forms with mineral acid on the materia medica among the present invention, and the example of described mineral acid includes but not limited to: hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid, phosphoric acid etc.; Or the salt that forms with organic acid, described organic acid example includes but not limited to: acetic acid, trifluoroacetic acid, propanoic acid, glycolic, acetone acid, oxalic acid, maleic acid, propylene glycol, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethyl sulfonic acid, p-methyl benzenesulfonic acid, salicylic acid etc.Mesylate most preferably wherein.
Chemical compound of the present invention or its pharmaceutically acceptable salt can the pure compound form or the appropriate drug compositions carry out administration, but preferably with the form administration of compositions, to reduce the toxic and side effects of active medicine.
The preparation that chemical compound of the present invention or compositions can adopt any acceptable administering mode or be used for similar purposes carries out.Therefore, the administering mode that adopts can select through port, nose, parenteral and local approach with solid, semisolid, lyophilized powder or liquid dosage form administration, for example, tablet (as conventional tablet, dispersible tablet, fast-release tablet, slow releasing tablet), capsule, powder agent, granule, solution, suspensoid or aerosol agent etc., the preferred dosage unit dosage form that adopts is applicable to the simple administration of exact dose.Per unit dosage dosage form can comprise the active component of 20-100mg, preferably includes 30-80mg, more preferably comprises 40-60mg.Compositions can comprise conventional pharmaceutical carrier or excipient and as the chemical compound of the present invention of active component, in addition, also can comprise other medicament, carrier, auxiliary agent etc.
Usually, according to required administering mode, pharmaceutically acceptable compositions will comprise The compounds of this invention or its pharmaceutically acceptable salt of about 1-99wt%, and the suitable pharmaceutical excipient of 99-1 wt%.Preferred composition comprises The compounds of this invention or the pharmaceutically acceptable salt of about 5-75 wt%, and all the other are suitable pharmaceutical excipient.
Preferred administering mode is an oral administration.For oral administration, comprise that acceptable composition is to form by the excipient that adds any common employing on the materia medica of chemical compound of the present invention or its pharmaceutically acceptable salt, the example of described excipient is pharmaceutical grade mannitol, lactose, starch, pre-gelatinized starch, magnesium stearate, saccharin sodium, Talcum, cellulose ether derivative, glucose, gelatin, sucrose, citrate, propyl gallate etc.This compositions can adopt forms such as solution, suspending agent, tablet, granule, capsule, powder agent, slow releasing preparation.
Preferred said composition is capsule or tablet, thereby it also can comprise diluent such as lactose, sucrose, dicalcium phosphate etc.; Disintegrating agent such as cross-linking sodium carboxymethyl cellulose or derivatives thereof; Lubricant such as magnesium stearate etc.; With binding agent such as starch, arabic gum, polyvinylpyrrolidone, gelatin, cellulose ether derivative etc.
The pharmaceutical composition that can adopt the liquid form administration for example can by means such as dissolving, dispersion with chemical compound of the present invention or its pharmaceutically acceptable salt (about 0.5-20%) and optional medicinal auxiliary agent dissolving, be scattered in the carrier, the example of carrier is water, saline, dextrose hydrate, glycerol, ethanol etc., thereby forms solution or suspension.
If necessary, pharmaceutical composition of the present invention also can comprise a spot of auxiliary substance, as wetting agent or emulsifying agent, pH buffer agent, antioxidant etc., for example: citric acid, Arlacel-20, Emulphor FM, butylation hydroxy benzenes etc.
The actual fabrication method of such dosage form is that those skilled in the art is known or tangible, for example can be referring to following document: Remington ' s Pharmaceutical Sciences, 18th Ed., (Mack Publishing Company, Easton, Pennsylvania, 1990).In any case according to technology of the present invention, the compositions of institute's administration will comprise chemical compound of the present invention or its pharmaceutically acceptable salt for the treatment of effective dose, to be used for the treatment of male sexual disorder.
The clinical research of 100 pairs of double-blind trials shows that medicine total effective rate of the present invention is more than 80%, but also has the advantage that dosage is little, rapid-action, toxic and side effects is little.Accidental side effect is nasal obstruction, face hyperemia, slight nauseating, and excess is taken and can be caused tachycardia.
By the description of following examples, it is more obvious that objects and advantages of the present invention will become, but scope of the present invention is not limited to this.
Embodiment 1
Present embodiment illustrates the preparation process of representative combination of oral medication, and described compositions comprises chemical compound of the present invention or its pharmaceutically acceptable salt, for example phentolamine mesylate:
A, composition %wt./wt.
Chemical compound 20.0% of the present invention
Lactose 79.5%
Magnesium stearate 0.5%
Mentioned component is mixed, and charge in the duricrust gelatine capsule, each capsules comprises 100mg.
B, composition %wt./wt.
Chemical compound 20.0% of the present invention
Magnesium stearate 0.9%
Starch 8.6%
Lactose 69.6%
PVP (polyvinylpyrrolidone) 0.9%
Other composition except that magnesium stearate is merged, and water carries out pelletize as granulation liquid.Be dried then, mix with magnesium stearate again, form tablet with suitable tablet machine.
C, composition
Chemical compound 0.4g of the present invention
Propylene glycol 20.0g
PEG400 20.0g
PS 1.0g
Water is to 100ml
With compound dissolution of the present invention in propylene glycol, PEG400 and PS.The water that under agitation adds capacity then obtains the solution of 100ml, with its filtration, and bottling.
D, composition %wt./wt.
Chemical compound 20.0% of the present invention
Oleum Arachidis hypogaeae semen 78.0%
Span?60?????????????2.0％
With the mentioned component fusion, mix, in the SEC of packing into.
E, composition %wt./wt.
Chemical compound 1.0% of the present invention
Methyl or carboxymethyl cellulose 2.0%
0.9% saline is to 100ml
Compound dissolution of the present invention in cellulose/saline solution, is filtered, and bottling is used.
Embodiment 2
Present embodiment illustrates the preparation of drug combination process of representative parenteral canal drug administration, and described compositions comprises chemical compound of the present invention or its pharmaceutically acceptable salt, for example phentolamine mesylate:
Composition
Chemical compound 0.2g of the present invention
Propylene glycol 20.0g
PEG400 20.0g
PS 1.0g
0.9% saline solution is to 100ml
With compound dissolution of the present invention in propylene glycol, PEG400 and PS.0.9% saline solution that under agitation adds capacity then obtains the I.V. solution of 100ml, with its membrane filtration filtration of material by 0.2 μ, packs under aseptic condition.
Embodiment 3
Present embodiment illustrates the preparation of drug combination process of representative insufflation, and described compositions comprises chemical compound of the present invention or its pharmaceutically acceptable salt, for example phentolamine mesylate:
Composition %wt./wt.
Micronized The compounds of this invention 1.0%
Micronized lactose 99.0%
Two kinds of compositions are ground, mix, be packaged in the insufflator that has dosing pump.
Embodiment 4
Present embodiment illustrates the preparation of drug combination process of representative spray form, and described compositions comprises chemical compound of the present invention or its pharmaceutically acceptable salt, for example phentolamine mesylate:
Composition %wt./wt.
Chemical compound 0.005% of the present invention
Water 89.995%
Ethanol 10.000%
Compound dissolution of the present invention in ethanol, is mixed water.Then with preparation packing in having the aerosol apparatus of dosing pump.
Embodiment 5
Present embodiment illustrates the preparation of drug combination process of representative aerosol form, and described compositions comprises chemical compound of the present invention or its pharmaceutically acceptable salt, for example phentolamine mesylate:
Composition %wt./wt.
Chemical compound 0.10% of the present invention
Propellant 11,/12 98.90%
Oleic acid 1.00%
Chemical compound of the present invention is scattered in oleic acid and the propellant.Then the mixture that forms is poured in the aerosol container that has metering valve.
Embodiment 6
Phentolamine mesylate is to the influence of male Mus sexual function
The healthy male Wistar rat of optional maturation (is purchased the Experimental Animal Center in Chinese Radiation Protection Research Inst, 3 monthly ages, body weight 20.4 ± 11.3g).They are divided into 5 groups at random, every group 10, respectively by the phentolamine mesylate tablet that makes among the table 1 dosage gastric infusion embodiment 1 (every contains the 40mg active component) and Yohimbine sheet (Fujian Province's Putian City pharmaceutical factory, every contains 5.4mg 17 Alpha-hydroxy yohimbane-16 α-methyl formate hydrochlorate), matched group administration 0.5%CMC-Na solution, every Mus 1ml/100g.After the administration 15 minutes, male Mus was put into 55 * 35 * 20cm cage separately 5 minutes, it can be conformed, in every cage, add female Mus and the following index of opening entry then:
(1) is fed into male Mus from female Mus the time (incubation period) of ejaculation for the first time takes place;
Male Mus pounces on the number of times and the ejaculation frequency of catching female Mus in (2) 20 minutes;
Each group is pounced on the animal that catches, ejaculates and is pounced on and catch rate % and ejaculation rate % in (3) 20 minutes, and repeats to examine record in 1 hour, 2 hours after administration, carries out statistics t and checks.
Above-mentioned result of experiment sees Table 1 and 2.This test in night active phase carry out.Table 1: to the influence-1 of male rat mating ability (n=10, X ± SD)
T check: compare with matched group
*P＞0.05,
*P＜0.05,
* *P＜0.01 table 2: to the influence-1 of male rat mating ability (n=10, X ± SD)
| Group | Matched group | Yohimbine | Phentolamine mesylate | |||
| Dosage | ?????-- | ????????2 | ????????40 | ????????20 | ???????10 | |
| Incubation period (minute) | 20′ | ???4.2±2.2 | ????2.4±0.5 ** | ??1.2±0.4 *** | ??2.6±0.5 ** | ????1.6±0.5 *** |
| 1° | ???5.2±1.5 | ????3.4±1.1 *** | ??1.8±0.8 *** | ??3.0±1.6 *** | ????3.0±2.0 ** | |
| 2° | ???4.8±1.8 | ????2.8±1.6 ** | ??1.4±0.5 *** | ??2.4±1.3 *** | ????2.6±1.5 *** | |
| Pounce on and catch number of times | 20′ | ???4.5±5.6 | ????10.2±6.9 * | ??20.6±9.2 *** | ??13.9±11.2 ** | ????9.8±9.2 * |
| 1° | ???3.1±5.0 | ????11.8±9.6 ** | ??16.7±9.7 *** | ??11.7±8.5 *** | ????9.1±9.4 * | |
| 2° | ???1.9±3.3 | ????6.5±6.7 * | ??9.9±10.6 ** | ??11.9±12.3 ** | ????5.9±6.6 * | |
| Ejaculation frequency | 20′ | ???3.0±4.1 | ????9.8±6.8 ** | ??15.2±5.4 *** | ??11.4±9.7 ** | ????8.0±7.5 * |
| 1° | ???2.3±3.8 | ????10.1±5.5 *** | ??11.5±6.2 *** | ??9.6±7.3 ** | ????6.6±6.6 * | |
| 2° | ???1.8±2.5 | ????4.3±3.6 * | ??5.8±5.6 * | ??10.9±12.9 ** | ????4.2±6.0 * | |
| Group | Matched group | Yohimbine | Phentolamine mesylate | |||
| Dosage | ????-- | ????2 | ????40 | ????20 | ????10 | |
| Pounce on the rate of catching (%) | 20′ | ????60 | ????80 | ????100 | ????80 | ????70 |
| 1° | ????40 | ????80 | ????90 | ????80 | ????70 | |
| 2° | ????40 | ????70 | ????80 | ????70 | ????60 | |
| Ejaculation rate (%) | 20′ | ????50 | ????80 | ????100 | ????80 | ????70 |
| ?1° | ????40 | ????70 | ????90 | ????80 | ????70 | |
| ?2° | ????40 | ????60 | ????80 | ????70 | ????60 | |
The above results shows, after never adult male Mus that mated with female Mus and female Mus meet, has 60% to begin to chase female Mus mating in back 6 minutes, and can finish ejaculation during this period.And behind the phentolamine mesylate of administration various dose, male Mus copulation can obviously improve, and shows as ejaculation latency and obviously shortens, and pouncing on of finishing in 20 minutes caught and the ejaculation frequency increase, and full group is pounced on the rate of catching, the ejaculation rate significantly increases, and sustainable 1-2 hour.Compare with similar medicine Yohimbine, the incubation period of medicine of the present invention is shorter, acts on stronger.
Embodiment 7
The acute toxicity testing of phentolamine mesylate
With purchasing in the Kunming mouse of Chinese Radiation Protection Research Inst's Experimental Animal Center body weight 19.7 ± 1.4g, male and female half and half.Through preliminary election, with 4 dosage groups, the phentolamine mesylate tablet that makes among the oral administration gavage administration embodiment 1 (every contains the 40mg active component), the agent between each dosage group is apart from being decided to be 1: 0.75, every group of 10 animals.The administration volume is the 0.5ml/20g body weight, observes continuously 10 days.(Sun Ruiyuan, quantitative pharmacology, People's Health Publisher, 1987:168 (NDST software)) adds up experimental result according to the Blise statistic law, measures the LD that oral stomach is irritated
50Be 6.73 (5.92-7.63) g/kg.
Measure the LD of subcutaneous injection route of administration according to method same as described above
50, its value is 2.17 (1.95-2.41) g/kg.
Claims (5)
1, the application of alpha-2-adrenoceptor blocker in the medicine of preparation treatment male sexual disorder, wherein said alpha-2-adrenoceptor blocker is an acceptable salt on phentolamine, tolazoline, phenoxybenzamine or its materia medica.
2, application as claimed in claim 1, wherein, described alpha-2-adrenoceptor blocker is an acceptable salt on phentolamine or its materia medica.
3, application as claimed in claim 2, wherein, described alpha-2-adrenoceptor blocker is a phentolamine mesylate.
4, as the described application of arbitrary aforementioned claim, wherein, with the form administration of tablet or capsule.
5, application as claimed in claim 4, wherein, per unit dosage comprises the described alpha-2-adrenoceptor blocker of 20-100mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99107479 CN1274581A (en) | 1999-05-20 | 1999-05-20 | Application of Alpha-adrenaline receptor blocking agent in preparing medicine for man's sexual dysfunction |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 99107479 CN1274581A (en) | 1999-05-20 | 1999-05-20 | Application of Alpha-adrenaline receptor blocking agent in preparing medicine for man's sexual dysfunction |
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| CN1274581A true CN1274581A (en) | 2000-11-29 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1872107B (en) * | 2006-04-21 | 2011-04-20 | 贵州神奇集团控股有限公司 | Chinese and Western compound preparations of alpha receptor blocking pharmacon, preparation method, and application |
-
1999
- 1999-05-20 CN CN 99107479 patent/CN1274581A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1872107B (en) * | 2006-04-21 | 2011-04-20 | 贵州神奇集团控股有限公司 | Chinese and Western compound preparations of alpha receptor blocking pharmacon, preparation method, and application |
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