CN1606981A - Use of phentolamine mesylate as therapeutic agent of feminine sterility - Google Patents
Use of phentolamine mesylate as therapeutic agent of feminine sterility Download PDFInfo
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- CN1606981A CN1606981A CN 200310111744 CN200310111744A CN1606981A CN 1606981 A CN1606981 A CN 1606981A CN 200310111744 CN200310111744 CN 200310111744 CN 200310111744 A CN200310111744 A CN 200310111744A CN 1606981 A CN1606981 A CN 1606981A
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- phentolamine mesylate
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- phentolamine
- infertility
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- PPWLAQVKIFDULF-UHFFFAOYSA-N 2-phenyl-1h-pyrrolo[2,3-b]pyridine Chemical compound N1C2=NC=CC=C2C=C1C1=CC=CC=C1 PPWLAQVKIFDULF-UHFFFAOYSA-N 0.000 title claims description 83
- 229960003056 phentolamine mesylate Drugs 0.000 title claims description 75
- 239000003814 drug Substances 0.000 title claims description 21
- 230000036512 infertility Effects 0.000 title claims description 10
- 229940124597 therapeutic agent Drugs 0.000 title 1
- 239000000829 suppository Substances 0.000 claims abstract description 4
- 235000015110 jellies Nutrition 0.000 claims abstract description 3
- 239000008274 jelly Substances 0.000 claims abstract description 3
- 229960001999 phentolamine Drugs 0.000 claims abstract 3
- MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 claims abstract 3
- 238000002360 preparation method Methods 0.000 claims description 19
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- 208000000509 infertility Diseases 0.000 claims description 9
- 231100000535 infertility Toxicity 0.000 claims description 9
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- 239000002464 receptor antagonist Substances 0.000 claims description 3
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- 150000003839 salts Chemical group 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
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- -1 hydrochlorate Chemical class 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 229960002312 tolazoline Drugs 0.000 claims description 2
- JIVZKJJQOZQXQB-UHFFFAOYSA-N tolazoline Chemical compound C=1C=CC=CC=1CC1=NCCN1 JIVZKJJQOZQXQB-UHFFFAOYSA-N 0.000 claims description 2
- 238000010276 construction Methods 0.000 claims 3
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims 1
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- 229910019142 PO4 Inorganic materials 0.000 claims 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 1
- QZVCTJOXCFMACW-UHFFFAOYSA-N Phenoxybenzamine Chemical compound C=1C=CC=CC=1CN(CCCl)C(C)COC1=CC=CC=C1 QZVCTJOXCFMACW-UHFFFAOYSA-N 0.000 claims 1
- 150000003973 alkyl amines Chemical class 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 238000005660 chlorination reaction Methods 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims 1
- 229960003418 phenoxybenzamine Drugs 0.000 claims 1
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- 239000010452 phosphate Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 208000007984 Female Infertility Diseases 0.000 abstract 1
- 206010021928 Infertility female Diseases 0.000 abstract 1
- MLHBDHJHNDJBLI-UHFFFAOYSA-N leucinocaine Chemical compound CCN(CC)C(CC(C)C)COC(=O)C1=CC=C(N)C=C1 MLHBDHJHNDJBLI-UHFFFAOYSA-N 0.000 abstract 1
- 229950006997 leucinocaine Drugs 0.000 abstract 1
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical group CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Said invention relates to the medical use of leucinocaine phentolamine of treating female infertility, which can be used in external form of suppository, jelly agent and effervesce tablet, and oral taking form of all body administration.
Description
● invention field
Phentolamine mesylate is loose block of white or off-white color or powder.Pharmacological action is the alpha-receptor antagonist, vasorelaxation action is arranged, it is strong to adrenolytic effect benodaine or tolazoline, can obviously reduce peripheral vascular resistance, strengthen around blood volume, also direct vasorelaxation action is arranged, particularly expand small artery and blood capillary, the blood flow of increase tissue, microcirculation improvement.Be applicable to the treatment vasospasm disease clinically, as Raynaud's disease, brothers' method dark purple, endarteritis obliterans, initial stage arteriosclerotic gangrene, extremity trophic ulcer, decubital ulcer, cold injury, toxic shock etc.The diagnosis of pheochromocytoma, and the ablation of tumors operation time prevents hypertensive crisis.
Phentolamine mesylate has the diastole effect to blood vessel, also is used to the male sexual disorder that causes because of diabetes, hypertension or because of reasons such as anxieties clinically, is applicable to the treatment of male erectile dysfunction.This medicine is not subjected to gonadal hormone, emotion and neural influence, can keep effective erection after the medication, and this medicine is rapid-action, side effect is little, take safety.
In clinical use, we find that the phentolamine mesylate external also has good therapeutic indifference, improves the effect of life quality for the women, we have developed the external preparation that uses at the women to this, further animal experiment and clinical observation are found, after using the phentolamine mesylate external preparation, weight, pregnant number and the fertility rate in ovary uterus ovulated, increased in pregnancy rate, the promotion that can obviously improve jenny, shows that phentolamine mesylate can be used for the treatment of infertility.
● summary of the invention
The present invention is the new medicinal mode of phentolamine mesylate.This mode is to adopt phentolamine mesylate to be used for the treatment of infertility.The preparation that employing contains phentolamine mesylate is used for the treatment of infertility clinically, this preparation can be contain one or more adjuvant or and the drug regimen of excipient, wherein contain effervescent tablet, suppository, jelly, spray that phentolamine mesylate 10mg-2g/ props up, or be the external preparation of substrate with Gel mile.Or wherein contain ejection preparations such as powder pin that phentolamine mesylate 10mg-2g/ props up, freeze-dried powder, injection.Or wherein contain the oral formulations such as tablet, capsule, dispersible tablet, effervescent tablet of phentolamine mesylate 10mg-2g/ sheet.Such drug use mode is applicable to too with the phentolamine mesylate to be the various salt of a series of derivative compound formulas of precursor structure.
● embodiment
The preparation of example one, phentolamine mesylate vaginal tablet, bolt, effervescent tablet etc.
Prescription one, phentolamine mesylate vaginal suppository
Phentolamine mesylate 2g
No. 1, Tween class suppository base is an amount of
Get Tween class suppository base and melt in water-bath for No. 1, the substrate and the phentolamine mesylate fine powder of the fusing that takes a morsel during 50 ℃ of left and right sides are ground into pasty state, join in the substrate of fusing, stir evenly, injection is coated with the bolt film that nuzzles up, cooled and solidified with aqueous paraffin wax in advance, wipe off, take out, packing promptly.This prescription dose can be made 100.
Prescription two: phentolamine mesylate vaginal suppository
Phentolamine mesylate 2g
No. 2, Tween class suppository base is an amount of
Earlier with No. 2 heating in water bath fusings of Tween class suppository base, fully stir, when treating that temperature is reduced to 50 ℃ of left and right sides, be ground into pasty state, add again in the remaining substrate with a small amount of substrate and phentolamine mesylate that melts, after stirring evenly, inject and be coated with the bolt mould that nuzzles up with aqueous paraffin wax in advance, cooled and solidified, strickling, take out, packing promptly.
Prescription three, phentolamine mesylate vaginal suppository
Phentolamine mesylate 2g
Glycerol gelatin matrix is an amount of
With glycerol gelatin matrix heat fused in water-bath, treat that temperature reduces to about 50 ℃, take out a small amount of substrate and the phentolamine mesylate fine powder stirs into even pasty state, to remain the substrate gradation again and add, and, stir evenly back injection lubricant and be coated with the suppository film that nuzzles up with adding with stirring, solidify, scrape scale, demoulding, packing is promptly.This formula ratio can be made 100.
Other substrate such as No. 1, the also available semi-synthetic fatty glyceride of glycerol gelatin matrix, Polyethylene Glycol substrate replace.
Prescription four, phentolamine mesylate vaginal suppository
Phentolamine mesylate 2g
Glycerol gelatin matrix is an amount of
Tween-80 (Tween-80) 8ml
Glycerin gelatine is made fusing with heating in water bath.Phentolamine mesylate and Tween-80 mixed grinding.Add in the ethanol, after the dissolving, be ground into pastel, slowly pour in the above-mentioned hot glycerine gelatin substrate, stir, in water-bath, leave standstill, treat bubble collapse after, irritate mould, cooling is solidified, wipe off, the demoulding, packing is promptly.
Prescription five: phentolamine mesylate vaginal suppository
Phentolamine mesylate 20g
Glycerol gelatin matrix is an amount of
Tween-80 (Tween-80) 8ml
No. 1 200g of Polyethylene Glycol suppository base
With No. 1 heating of Polyethylene Glycol suppository base, make its fusing, get phentolamine mesylate and be ground into fine powder; Add and melted to such an extent that the Polyethylene Glycol suppository base is ground into pasty state No. 1 in right amount, slowly add residue substrate, after stirring evenly, in the impouring bolt film, solidify in the time of 60 ℃, wipe off, take out, packing promptly.This prescription dose can be made into 1000.
Prescription six, phentolamine mesylate vaginal tablet
Phentolamine mesylate 50g
Starch 200g
Lactose 50g
Starch slurry (10%) 200ml
Pulvis Talci 20g
With phentolamine mesylate, lactose, starch, porphyrize is crossed 80 ∽, 100 mesh sieves respectively, with the equivalent method of progressively increasing phentolamine mesylate and lactose is mixed thoroughly, mix with starch again, cross 80 mesh sieve mixings, it is an amount of to add starch slurry, makes granule with 16 ∽, 18 mesh sieves, in dry below 60 ℃, granulate adds the Pulvis Talci mixing, claims gross weight, the calculating sheet is heavy, suppresses 1000 promptly.
Prescription seven, the preparation of phentolamine mesylate effervescent tablet
Phentolamine mesylate 6 grams
Tartaric acid 4.2 grams
Sodium bicarbonate 17.5 grams
Tween 80 1.2 grams
Polyvinylpyrrolidone (PVP) 3.2 grams
Low-substituted hydroxypropyl cellulose (LHPC) 1.6 grams
Magnesium stearate 0.64 gram
Mentioned reagent is fully mixed, and tabletting is made 100 altogether.Every contains phentolamine mesylate 60mg.
Prescription eight, the preparation of phentolamine mesylate gelatum agent
Phentolamine mesylate 600 grams
Edible Gel mile 100 000 grams
With the some adjustings of food coloring, after fully mixing, be prepared into 10 000 gelatum agents, the sterilization packing.
The preparation of prescription nine, phentolamine mesylate spray
The phentolamine mesylate raw material is pressed following formulation spray:
Phentolamine mesylate 300g
Chitin 100g
Ethanol 300ml
Add water to 30 000ml
With the some adjustings of food coloring, after fully mixing, sterilization is divided in the aerosol container of 3ml, is prepared into 10 000 sprays.Spray bottle is selected the 3ml standard, and the selection spout is that each spray amount is the shower nozzle of 200 μ l.
Example two, phentolamine mesylate drug action test
Test one: phentolamine mesylate promotes mice fertility experiment
Select 30 of the female Kunming mouses of body weight 16-28g, random packet, by every mice 2mg/, 6mg/ dosage vaginal suppository mode administration only, every day 1 time is after continuous 5 days, per 3 female Mus and 1 male Mus mated copulation seven, continue during this time to give male Mus perfusion, take out female Mus after the drug withdrawal, grouping was raised after 7 days, laparotomy inspection is respectively organized the animal pregnancy number of mice, and compares with matched group.
The short early pregnancy effect of table 1, phentolamine mesylate (x ± s)
| Grouping | Dosage | Number of animals | The pregnant rat number |
| Matched group | ?/ | ????10 | ????2 |
| Phentolamine mesylate | 2mg/ only | ????10 | ????5 |
| Phentolamine mesylate | 6mg/ only | ????10 | ????8 |
Test two, the phentolamine mesylate influence open to mouse vagina
30 of female Kunming mouses are divided into 3 groups at random.By every mice 2mg/ only, 6mg/ dosage vaginal suppository mode administration every day only 1 time, continuous 5 days.Observe the vagina opening status since morning every day on the 3rd.Record wide-open number of animals of vagina and time, data are the t check through between group.
The influence that table 2, phentolamine mesylate are opened female Mus vagina (x ± S)
| Grouping | Dosage | Number of animals | The open fully number of animals of vagina | Average open number |
| Matched group | ???/ | ????10 | ????2 | ???0.2±0.4 |
| Phentolamine mesylate | 2mg/ only | ????10 | ????6 | ???0.6±0.5 |
| Phentolamine mesylate | 6mg/ only | ????10 | ????7 | ???0.7±0.5 * |
*p＜0.05
Opening has obvious facilitation to the heavy dose of group of phentolamine mesylate to female Mus vagina as seen from the table.
Test three, phentolamine mesylate promote the influence of mice ovulation
Get 30 of the female Kunming mouses of body weight 14-16g, be divided into 3 groups at random.About at 9 o'clock in morning every day, and the subcutaneous injection human chorionic gonadotropin (the biochemical factory in Shanghai, HCG) 10IU/ is only, every day 1 time, continuous 2 days, 9 o'clock on the 3rd began, press 2mg/ only, the dosage vaginal suppository mode administration of a 6mg/ mice, every day 1 time, continuous 5 days, last administration 2h put to death mice, back of the body position is fixing, win fallopian tube, ovary and uterus are tiled on the filter paper by physiological location.Clip bilateral fallopian tube is in the horizontalization ware normal saline.One oviductus lateralis is placed on the microscope slide, add a coverslip under anatomic microscope, drip one of normal saline, find out the fallopian tube edge with low power lens earlier, amplification is counted the ovum number piecemeal again.Data are check through between group, lists in table 3.As seen from Table 3, the phentolamine mesylate heavy dose is organized ovum number, with matched group notable difference is arranged.Show that this medicine can obviously promote ovulation, improves female Mus reproductive function.
The facilitation that table 3, phentolamine mesylate are ovulated to female Mus (x ± S)
| Grouping | Dosage | Number of animals | Ovum number in the fallopian tube |
| Matched group | ?/ | ????10 | ?????12.4±3.6 |
| Phentolamine mesylate | 2mg/ only | ????10 | ?????15.7±6.3 |
| Phentolamine mesylate | 6mg/ only | ????10 | ?????18.4±4.7 * |
*P＜0.05
Test four, phentolamine mesylate promote the influence of ovulation failure mice
Mice ovulation failure model: take out and give birth to totally 50 of back 7 days Kunming kind female mices, in cervical region subcutaneous injection testosterone propionate (1mg/ only), 8 back continuous review 2 cycles of vaginal exfoliated cell smear in week, only shown as nuclear epithelium or cuticulated epithelium and aperiodicity variation person is considered as ovulation failure.Divide 2 groups at random with 20 of mices confirming as ovulation failure, be respectively 10 every group of test group and matched groups.Test group is pressed the dosage vaginal suppository mode administration of 6mg/ mice, every day 1 time, after continuous 5 days, observe the ovulation index: 1, vaginal smear: each group is all after the vaginal suppository administration, every day at the upper and lower noon is respectively done 1 vaginal exfoliated cell smear inspection, and whether observe has cyclically-varying.2, calculate oocyte number in the fallopian tube: 2 groups all after administration the 5th day, mice bilateral fallopian tube is taken out in operation, is put between two microscope slides (pressed disc method), low power microscope is observed the ovulation situation down.As ovulating, calculate the oocyte number in the fallopian tube lumen.Adopt X between each group
2Check, variance analysis and t check.Result: 1, vaginal exfoliated: after the medication of phentolamine mesylate group in 5 days, mouse vagina exfoliative cyte smear is cyclically-varying person, be 8 (80%), matched group is 3 (30%), and phentolamine mesylate group and matched group relatively have significant difference (p＜0.05).2, oocyte number in the fallopian tube: 8～16 of phentolamine mesylate groups, average 14.3,7～12 of matched groups, average 8.8, two groups of comparing differences have significance (p＜0.05).3, phentolamine mesylate is to the influence of mice body weight and internal organs, and during the experiment beginning, phentolamine mesylate group, control group mice average weight are respectively 32.8 ± 3.6g and 33.2 ± 3.1g, and 2 groups are compared there was no significant difference (p＞0.05).The average weight that experiment back is 2 groups is respectively 33.3 ± 3.5g and 34.9 ± 2.1g, 2 groups of there was no significant differences (p＞0.05) more still. and same group of experiment beginning compared with the experiment back, and difference does not have significance (p＞0.05) yet.The test group Mus heart, liver, nephridial tissue are checked, compare with normal female Mus, and be all no abnormal.But phentolamine mesylate can obviously increase mouse uterine weight, during the experiment beginning, phentolamine mesylate group, the average uterus weight 18.4 ± 4.3mg of control group mice and 17.2 ± 3.5mg, the 2 groups of average uterus weight 28.1 ± 7.4mg of mice in experiment back and 21.3 ± 5.3mg, two groups relatively, and difference has significance (p＜0.05).
Test five, phentolamine mesylate are to the influence of ovary weight
30 of female Kunming mouses are divided into 3 groups at random, are respectively 2 groups of test group and matched group.Test group press 2mg/ only, the dosage vaginal suppository mode administration of a 6mg/ mice, every day 1 time, continuous 5 days.Put to death mice after 5 days and win ovary, claim its weight in wet base in torsion balance, data are listed in table 4 through the t check.2 dosage groups of phentolamine mesylate all can obviously make female rat ovarian weight increase as seen from Table 4.
Table 4, phentolamine mesylate are to the influence of female rat ovarian weight (x ± s)
| Grouping | Dosage | Number of animals | Ovary weight (mg) |
| Matched group | ??/ | ????10 | ????16.4±4.1 |
| Phentolamine mesylate | 2mg/ only | ????10 | ????21.4±4.9 * |
| Phentolamine mesylate | 6mg/ only | ????10 | ????24.5±6.3 * |
*p＜0.05
Test six, phentolamine mesylate are to the restitution of rat reproductive system of damage
Select 60 of body weight 108-200g SD rats, the male and female sex ratio is 3: 1, mated copulation seven by per 3 female Mus and 1 male Mus, every morning is checked, the female Mus cage raising in addition that will have vaginal suppository to form, give mifepristone female Mus in conceived 7 days and carry out drug induced abortion, treat 7 days post-abortions of rat, continue female Mus and male Mus mated allowing it undergo another pregnancy.With the female Mus that carried out drug induced abortion for continuous three times as damaging endometrial rat model animal.Select wherein body weight at 200-240g, outward appearance, hair color, 20 female Mus that active state is close, be divided into 10 of 10 of matched groups and phentolamine mesylate groups at random, press the standard mode feeding after 10 days, the phentolamine mesylate group is pressed the dosage vaginal suppository mode administration of 20mg/ rat, every day 1 time, after continuous 5 days, in addition by every day 2 female Mus join with 1 new male Mus and mated copulation 7, during the administration group continue medication, day by day check the conceived situation of female Mus, female Mus is taken out in the no longer administration of conceived rat after 7 days, the animal pregnancy number that laparotomy inspection on the 7th is respectively organized rat is raised in grouping again, and there was no significant difference relatively being arranged with matched group, data are checked through t.Result: rat animal pregnancy number: several 0～16 of phentolamine mesylate group rat animal pregnancy, average 8.7, several 0～12 of control rats animal pregnancy, average 3.8, two groups of comparing differences have significance (p＜0.05).
Test seven, phentolamine mesylate are to the restitution of the impaired reproductive function of women
Women's case A, 28 years old, artificial abortion was once repeatedly done in not fertility as yet, and with habitual abortion.It has endometritis and the inner adhesion of cavity of uterus clinical examination, the ultrasound diagnosis of vagina, and endometrium thickness is less than 7mm, and menstruation and ovulation are normal.This case through behind the habitual abortion repeatedly to undergoing another pregnancy and fertility is lost confidence.By the administration of each 20mg vaginal suppository mode, one all 3-6 time, normality is lived and is not taked contraceptives, use continuously after 3 months, find menolipsis, find that through ultrasound diagnosis this case is conceived, by the test of color stream doppler ultrasound instrument, its uterine blood flow is improved, the Uterus wall enlarged in thickness.
Claims (6)
1, the new medicinal mode of phentolamine mesylate.This mode is to adopt phentolamine mesylate to be used for the treatment of infertility.
2, according to the drug use mode of claim 1, it is characterized in that it being to adopt the preparation that contains phentolamine mesylate to be used for the treatment of infertility clinically, this preparation can be contain one or more adjuvant or and the drug regimen of excipient, wherein contain effervescent tablet, suppository, jelly, spray that phentolamine mesylate 10mg-2g/ props up, or be the external preparation of substrate with Gel mile.
3, according to the drug use mode of claim 1, it is characterized in that it being to adopt the preparation that contains phentolamine mesylate to be used for the treatment of infertility clinically, this preparation can be contain one or more adjuvant or and the drug regimen of excipient, wherein contain ejection preparations such as powder pin that phentolamine mesylate 10mg-2g/ props up, freeze-dried powder, injection.
4, according to the drug use mode of claim 1, it is characterized in that it being to adopt the preparation that contains phentolamine mesylate to be used for the treatment of infertility clinically, this preparation can be contain one or more adjuvant or and the drug regimen of excipient, wherein contain the oral formulations such as tablet, capsule, dispersible tablet, effervescent tablet of phentolamine mesylate 10mg-2g/ sheet.
5, according to the drug use mode of claim 1, it is characterized in that such medicine can also be to contain the derivative compound that phentolamine is a precursor structure, the construction features of these chemical compounds shows as: I, be the various salt forms of phentolamine, comprise various salt such as hydrochlorate, phosphate, citrate.II, be to be the fugitive receptor antagonist of construction features with the imidazoline, as tolazoline etc.III, be to be the long-acting receptor antagonist of construction features with the chlorination alkylamine, bright etc. as phenoxybenzamine, the appropriate benzyl of Ethylenimine type phenol.
6, according to the described chemical compound of claim 5, it is characterized in that it being to adopt these chemical compounds can be prepared to multiple pharmaceutical dosage forms, this preparation can be contain one or more adjuvant or and the drug regimen of excipient, wherein contain the described chemical compound of claim 4, be used for the treatment of infertility clinically.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310111744 CN1606981A (en) | 2003-10-14 | 2003-10-14 | Use of phentolamine mesylate as therapeutic agent of feminine sterility |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200310111744 CN1606981A (en) | 2003-10-14 | 2003-10-14 | Use of phentolamine mesylate as therapeutic agent of feminine sterility |
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| CN1606981A true CN1606981A (en) | 2005-04-20 |
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| CN 200310111744 Pending CN1606981A (en) | 2003-10-14 | 2003-10-14 | Use of phentolamine mesylate as therapeutic agent of feminine sterility |
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