US3436462A - Normalizing or reduction of the abnormal permeability of persons having capillar fragility with para-di-hydroxybenzene sulfonate - Google Patents
Normalizing or reduction of the abnormal permeability of persons having capillar fragility with para-di-hydroxybenzene sulfonate Download PDFInfo
- Publication number
- US3436462A US3436462A US523947A US3436462DA US3436462A US 3436462 A US3436462 A US 3436462A US 523947 A US523947 A US 523947A US 3436462D A US3436462D A US 3436462DA US 3436462 A US3436462 A US 3436462A
- Authority
- US
- United States
- Prior art keywords
- para
- fragility
- capillar
- normalizing
- persons
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 title description 14
- 230000002159 abnormal effect Effects 0.000 title description 8
- 230000035699 permeability Effects 0.000 title description 8
- 229960003742 phenol Drugs 0.000 title 1
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 13
- 238000000034 method Methods 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 5
- 206010020565 Hyperaemia Diseases 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 210000000245 forearm Anatomy 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- HPNMFZURTQLUMO-UHFFFAOYSA-O diethylammonium Chemical compound CC[NH2+]CC HPNMFZURTQLUMO-UHFFFAOYSA-O 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 125000005210 alkyl ammonium group Chemical group 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-O triethanolammonium Chemical compound OCC[NH+](CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-O 0.000 description 2
- VZYDKJOUEPFKMW-UHFFFAOYSA-N 2,3-dihydroxybenzenesulfonic acid Chemical compound OC1=CC=CC(S(O)(=O)=O)=C1O VZYDKJOUEPFKMW-UHFFFAOYSA-N 0.000 description 1
- 206010007191 Capillary fragility Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
Definitions
- R in the above formula may be sodium, calcium, ammonium, alkylammonium, or alkanolammonium.
- the present invention concerns a process of acting on the vascular wall of the blood system of ill persons, by
- said process comprises administering to said persons compounds of the formula in which R is selected from the group consisting of sodium, calcium, ammonium, alkylammonium and alkanolammonium.
- sodium para-dihydroxybenzene sulfonate, calcium para-dihydroxybenzene sulfonate, ammonium para-dihydroxybenzene sulfonate, diethyl ammonium para-dihydroxybenzene sulfonate, and triethanolammonium para-dihydroxybenzene sulfonate are especially suitable for acting on the vascular wall by making its fragility become normal or by reducing its permeability, when such fragility or permeabilit are abnormally high.
- the compounds may be administered e.g. intramuscularly or intravenously (injectable solutions of 2 cc. with 250 mg. of active principle), per os in capsules of 250 mg, or even rectally with suppositories dosed at 500 mg.
- EXAMPLE 1 To a group of patients of different ages and sex, having a very high increase in capillary fragility, injection of a single .dose of 0.250 g. to 1 g. of diet'hylammonium para- Patented Apr. 1, 1969 dihydroxybenzene sulfonate was made. This injection causes the fragility to become normal in 70% of all cases, whereas with the other patients an increase in vascular resistance of the order of 50 to could be observed.
- EXAMPLE 2 In a group of patients, local hyperaemia is caused by applying an ointment of 5% tetrahydrofurfurylic ester of nictotinic acid to forearm skin. When these patients had received an intramuscular injection of 500 mg. of diethylammonium para-dihydroxybenzene sulfonate an hour before the same test had been repeated to the other forearm, it couldbe seen that the surface of the hyperaemia area was reduced by 45% with respect to the control test.
- the method for obtaining exact results with these tests comprises putting a dye on the hyperaemia surface, and transferring thereafter this dye spot to a millimeter paper, by direct contact.
- the surface of the dye spot can be measured with great precision.
- the comparison of the dye spot surfaces of the right and left forearm respectively (before and after administering the product) permits to determine exactly the percentage of the diminution.
- EXAMPLE 3 In another group of patients, local hyperaemia is caused by applying an ointment of 5% tetrahydrofurfurylic ester of nicotinic acid to forearm skin. When these patients had received an intramuscular injection of 500 mg. of ammonium para-dihydroxybenzene sulfonate an hour before the same test had been repeated to the other forearm skin, it could be seen that the surface of the hyperaemia area was reduced by 14.4 to 44.7%, the mean value being 30%.
- a similar diminution is obtained if the patients receive either 16 tablets of 250 mg. of said product in a rhythm of two tablets each sixth hour, or one suppository containing 500 mg. of said product four times a day during two days.
- Example 1 clearly demonstrate that the above-mentioned chemicals normalize capillar fragility when it has become abnormal for some reason or other.
- Examples 2, 3 and 4 show that the vascular permeability remains reduced if one of the above-mentioned chemicals is applied.
- a method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of a compound of the formula I OH ' comprises administering to said person an effective amount of calcium para-dihydroxybenzene sulfonate.
- a method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of ammonium para-dihydroxybenzene sulfonate.
- a method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of diethylammonium para-dihydroxybenzene sulfonate.
- a method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of triethanolammonium para-dihydroxybenzene sulfonate.
Description
United States Patent U.S. Cl. 424-316 6 Claims ABSTRACT OF THE DISCLOSURE Process of acting on the vascular wall of the blood system of ill persons to normalize the capillar fragility, or to reduce the abnormal permeability of the wall, by administering compounds of the formula:
I OH
R in the above formula may be sodium, calcium, ammonium, alkylammonium, or alkanolammonium.
This application is a continuation-in-part of application Ser. No. 329,391, filed Dec. 10, 1963, now Patent No. 3,351,526, and application Ser. No. 202,981, filed June 18, 1962, now Patent No. 3,354,201, the latter of which is a continuation-in-part of application Ser. No. 2, filed J an. 4, 1960, now abandoned.
The present invention concerns a process of acting on the vascular wall of the blood system of ill persons, by
making the capillar fragility become normal or by reducing an abnormal permeability of the wall.
According to the invention, said process comprises administering to said persons compounds of the formula in which R is selected from the group consisting of sodium, calcium, ammonium, alkylammonium and alkanolammonium.
It has been found, that among the compounds having said general formula, sodium para-dihydroxybenzene sulfonate, calcium para-dihydroxybenzene sulfonate, ammonium para-dihydroxybenzene sulfonate, diethyl ammonium para-dihydroxybenzene sulfonate, and triethanolammonium para-dihydroxybenzene sulfonate are especially suitable for acting on the vascular wall by making its fragility become normal or by reducing its permeability, when such fragility or permeabilit are abnormally high.
The compounds may be administered e.g. intramuscularly or intravenously (injectable solutions of 2 cc. with 250 mg. of active principle), per os in capsules of 250 mg, or even rectally with suppositories dosed at 500 mg.
EXAMPLE 1 To a group of patients of different ages and sex, having a very high increase in capillary fragility, injection of a single .dose of 0.250 g. to 1 g. of diet'hylammonium para- Patented Apr. 1, 1969 dihydroxybenzene sulfonate was made. This injection causes the fragility to become normal in 70% of all cases, whereas with the other patients an increase in vascular resistance of the order of 50 to could be observed.
These effects persist for two days and more, whereafter they diminish slowly during five or six days to values clearly inferior of the initial ones. This shows that the effects are not due to a mere vaso-constrictorial action.
To another group of patients, which had similar alterations of the capillar fragility, were given during two days eight tablets per day containing each 250 mg. of diethylammonium para-dihydroxybenzene sulfonate. Thereby, substantially the same results were obtained as with the above-mentioned injection.
EXAMPLE 2 In a group of patients, local hyperaemia is caused by applying an ointment of 5% tetrahydrofurfurylic ester of nictotinic acid to forearm skin. When these patients had received an intramuscular injection of 500 mg. of diethylammonium para-dihydroxybenzene sulfonate an hour before the same test had been repeated to the other forearm, it couldbe seen that the surface of the hyperaemia area was reduced by 45% with respect to the control test.
The method for obtaining exact results with these tests comprises putting a dye on the hyperaemia surface, and transferring thereafter this dye spot to a millimeter paper, by direct contact. Thus, the surface of the dye spot can be measured with great precision. The comparison of the dye spot surfaces of the right and left forearm respectively (before and after administering the product) permits to determine exactly the percentage of the diminution.
A similar diminution is obtained if the patients receive either 16 tablets of 250 mg. of said product in a.
rhythm of two tablets each sixth hour, or one suppository containing 500 mg. of said product four times a day during two days.
EXAMPLE 3 EXAMPLE 4 In another group of patients, local hyperaemia is caused by applying an ointment of 5% tetrahydrofurfurylic ester of nicotinic acid to forearm skin. When these patients had received an intramuscular injection of 500 mg. of ammonium para-dihydroxybenzene sulfonate an hour before the same test had been repeated to the other forearm skin, it could be seen that the surface of the hyperaemia area was reduced by 14.4 to 44.7%, the mean value being 30%.
A similar diminution is obtained if the patients receive either 16 tablets of 250 mg. of said product in a rhythm of two tablets each sixth hour, or one suppository containing 500 mg. of said product four times a day during two days.
The results of Example 1 clearly demonstrate that the above-mentioned chemicals normalize capillar fragility when it has become abnormal for some reason or other. Likewise, Examples 2, 3 and 4 show that the vascular permeability remains reduced if one of the above-mentioned chemicals is applied.
The sodium and calcium salt of para-dihydroxybenzene sulfonate were tested as described in Examples 1 to 4 above, and results very similar to those mentioned in 3 these four examples had been obtained with said sodium and calcium salt.
What I claim is:
1. A method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of a compound of the formula I OH ' comprises administering to said person an effective amount of calcium para-dihydroxybenzene sulfonate.
4. A method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of ammonium para-dihydroxybenzene sulfonate.
5. A method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of diethylammonium para-dihydroxybenzene sulfonate.
6. A method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of triethanolammonium para-dihydroxybenzene sulfonate.
References Cited Chem. Abst., 60:1652h-1653a, 1964.
ALBERT T. MEYERS, Primary Examiner.
S. J. FRIEDMAN, Assistant Examiner.
U.S. Cl. X.R. 424315
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52394766A | 1966-02-01 | 1966-02-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3436462A true US3436462A (en) | 1969-04-01 |
Family
ID=24087075
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US523947A Expired - Lifetime US3436462A (en) | 1966-02-01 | 1966-02-01 | Normalizing or reduction of the abnormal permeability of persons having capillar fragility with para-di-hydroxybenzene sulfonate |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3436462A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4005220A (en) * | 1973-02-20 | 1977-01-25 | Laboratorios Del Dr. Esteve, S.A. | Hemostatic compositions comprising salts of substituted hydroquinone sulfonic acid |
| US4128661A (en) * | 1977-11-22 | 1978-12-05 | Laboratories Om Societe Anonyme | (Bis-diethylamine)2,5-dihydroxybenzene-1,4-disulfonate, useful as a medicament against glaucoma |
| US4513007A (en) * | 1983-05-03 | 1985-04-23 | Laboratoires Om Sa | Method for treating heart disease |
| US4936866A (en) * | 1986-10-07 | 1990-06-26 | Exxon Chemical Patents Inc. | Lactone modified polymeric amines useful as oil soluble dispersant additives |
| EP1637133A3 (en) * | 1996-04-03 | 2007-07-11 | Laboratorios Del Dr. Esteve, S.A. | Use of 2,5-dihydroxybenzenesulfonic acid derivatives for the preparation of medicaments for normalising the endothelial function, for the treatment of sexual dysfunction and vascular complications of diabetes, and vascular disorders of endothelial origin |
-
1966
- 1966-02-01 US US523947A patent/US3436462A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4005220A (en) * | 1973-02-20 | 1977-01-25 | Laboratorios Del Dr. Esteve, S.A. | Hemostatic compositions comprising salts of substituted hydroquinone sulfonic acid |
| US4128661A (en) * | 1977-11-22 | 1978-12-05 | Laboratories Om Societe Anonyme | (Bis-diethylamine)2,5-dihydroxybenzene-1,4-disulfonate, useful as a medicament against glaucoma |
| US4513007A (en) * | 1983-05-03 | 1985-04-23 | Laboratoires Om Sa | Method for treating heart disease |
| US4936866A (en) * | 1986-10-07 | 1990-06-26 | Exxon Chemical Patents Inc. | Lactone modified polymeric amines useful as oil soluble dispersant additives |
| EP1637133A3 (en) * | 1996-04-03 | 2007-07-11 | Laboratorios Del Dr. Esteve, S.A. | Use of 2,5-dihydroxybenzenesulfonic acid derivatives for the preparation of medicaments for normalising the endothelial function, for the treatment of sexual dysfunction and vascular complications of diabetes, and vascular disorders of endothelial origin |
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