CA1064018A - Stabilizer for natural conjugated estrogens - Google Patents
Stabilizer for natural conjugated estrogensInfo
- Publication number
- CA1064018A CA1064018A CA263,029A CA263029A CA1064018A CA 1064018 A CA1064018 A CA 1064018A CA 263029 A CA263029 A CA 263029A CA 1064018 A CA1064018 A CA 1064018A
- Authority
- CA
- Canada
- Prior art keywords
- sodium acetate
- sulphates
- conjugated estrogens
- stabilizer
- natural conjugated
- 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
Links
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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Steroid Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
The use of sodium acetate as a stabilizing additive to alkali sulphates of natural conjugated estrogens particularly when they are stored in the dry state over a lengthy period of time.
The use of sodium acetate as a stabilizing additive to alkali sulphates of natural conjugated estrogens particularly when they are stored in the dry state over a lengthy period of time.
Description
The present invention relates to the use of sodiurn acetate for stabilizing alkali sulphates of natural conjuyated estro~ens and particularly to prevent them from decomposing when they are stored in the dry state for a lengthy period oE time.
Estrogen sulphates in the form oE their water-soluble sodium salts are contained in the urine oE pregnant mares.
A mixture of these natural conjugated estrogens which consists substantially of the 3-hemisulphates of the estro~ens estrone, equilin and equilenin and of their 17-dihydro derivatives :L7~-estradiol, 17~-equilol and 17~-equilenol, is obtained by extraction and in therapy it is used primarily for relieving the comp:Laints associated ~ith the climacterium. These mixtures do not always have the same composition and are therefore standardized by adding synthetically produced salts of other estrogen sulphates, for example, estrone sulphate. However, the fact that the alkali salts o~ these synthetic estrogen sulphates are not stable in the dry state and decompose while forming the corresponding estrogen and alkali hydrogen sulphate is a disadvantage~
Several proposals for improving the stability of these compo~mds are known, for example, by adding the urine of mares (Canadian Patents 691 988 and 922 627), N-methyl glucamine (US
Patent 3 024 257), other substituted amines (laid-open German Specification 1 918 291), amino acids (laid-open German Specifi-cation 1 937 519) or by producing the salts of quaternary ammonium bases (laid-open German Specification 1 ~32 740) instead of alkali salts of estrogen sulphates~ These processes either are technically expensive and re~uire relati~ely costly or non~
physiological additives or they result in compounds ~hich are only very difficultly soluble in water.
::
3Q The present invention provides a simple, ph~siologically unobjectionable stabilizer, which remains effective over an unlimited period of time.
_~ .
- 1- . ~:
- ~ - - -- . I . .. . , .. .. . .. .. - . . .
~69~
According to the present invention/ sodium acetate is used as a stabilizing additive to alkali sulphates o:E natural conjugated estrogens which prevents decomposition when storing said alkali sulphates in the dry state over a lengthy period of time. The stabilizer is suitably added in amounts from 0.5 to 50%, preferably from 2 to 10~, although an addition o~ even less than 0.5% should show an e~fect. Although larger amounts -than 50% do not impair the stabilizing effec-t, they are not necessary since the desired ef~ect is achieved with smaller amounts.
It is surprising that sodium acetate has such a marked stabilizing effect.
The preserving effect.of the stabilizer according to the invention is illustrated by the fact that, for example, estrone sulphate sodium was almost completely decomposed after three months at room temperature while estrone sulphate sodium with an addition of 5~ of sodium acetate showed no traces of . -decomposition under identical conditions of storage.
The sodium acetate used according to the invention :
is mixed with the estrogen, for example, by triturating and screening the dry components or by dissolving in a solvent such as methanol and by evaporating the solution to dryness or by .
dissolving in water and su~sequent freeze~drying.
. The invention is further illustrated by way of the following Examples. -EXample 1 : .
Estrogen sulphate sodium salts are stored at a room temperature o~ 23C with an addition of 5~o of sodium acetate .
for a period of up to three months.
Estrogen sulphate .s.odium .sa.lt:. :0. .3Ø 6Ø... 9.0 days.
~_ estrone 99 99(50) 99(20). 99(0) %
equilin 100 100(.95) lQ0(~0) 100~50?
equilenin 100 100 100 100 ~-estradiol 100 100 100 100 ~L~&~
The numbers represent the content oE the undecomposed estrogen sulphate sodium salt in the mixtures in percent.
For comparison, the numbers in parentheses represent the values for storage in an exsiccator over potassium hydroxide without the addition of sodium acetate.
Examp e 2 Estrone sulphate sodium salt is stored at 60CC with addition of varying amounts o~ sodium acetate.
Sodium acetate 0 30 days ¢'' ... . _. .... . .. .~
0.5 98 5
Estrogen sulphates in the form oE their water-soluble sodium salts are contained in the urine oE pregnant mares.
A mixture of these natural conjugated estrogens which consists substantially of the 3-hemisulphates of the estro~ens estrone, equilin and equilenin and of their 17-dihydro derivatives :L7~-estradiol, 17~-equilol and 17~-equilenol, is obtained by extraction and in therapy it is used primarily for relieving the comp:Laints associated ~ith the climacterium. These mixtures do not always have the same composition and are therefore standardized by adding synthetically produced salts of other estrogen sulphates, for example, estrone sulphate. However, the fact that the alkali salts o~ these synthetic estrogen sulphates are not stable in the dry state and decompose while forming the corresponding estrogen and alkali hydrogen sulphate is a disadvantage~
Several proposals for improving the stability of these compo~mds are known, for example, by adding the urine of mares (Canadian Patents 691 988 and 922 627), N-methyl glucamine (US
Patent 3 024 257), other substituted amines (laid-open German Specification 1 918 291), amino acids (laid-open German Specifi-cation 1 937 519) or by producing the salts of quaternary ammonium bases (laid-open German Specification 1 ~32 740) instead of alkali salts of estrogen sulphates~ These processes either are technically expensive and re~uire relati~ely costly or non~
physiological additives or they result in compounds ~hich are only very difficultly soluble in water.
::
3Q The present invention provides a simple, ph~siologically unobjectionable stabilizer, which remains effective over an unlimited period of time.
_~ .
- 1- . ~:
- ~ - - -- . I . .. . , .. .. . .. .. - . . .
~69~
According to the present invention/ sodium acetate is used as a stabilizing additive to alkali sulphates o:E natural conjugated estrogens which prevents decomposition when storing said alkali sulphates in the dry state over a lengthy period of time. The stabilizer is suitably added in amounts from 0.5 to 50%, preferably from 2 to 10~, although an addition o~ even less than 0.5% should show an e~fect. Although larger amounts -than 50% do not impair the stabilizing effec-t, they are not necessary since the desired ef~ect is achieved with smaller amounts.
It is surprising that sodium acetate has such a marked stabilizing effect.
The preserving effect.of the stabilizer according to the invention is illustrated by the fact that, for example, estrone sulphate sodium was almost completely decomposed after three months at room temperature while estrone sulphate sodium with an addition of 5~ of sodium acetate showed no traces of . -decomposition under identical conditions of storage.
The sodium acetate used according to the invention :
is mixed with the estrogen, for example, by triturating and screening the dry components or by dissolving in a solvent such as methanol and by evaporating the solution to dryness or by .
dissolving in water and su~sequent freeze~drying.
. The invention is further illustrated by way of the following Examples. -EXample 1 : .
Estrogen sulphate sodium salts are stored at a room temperature o~ 23C with an addition of 5~o of sodium acetate .
for a period of up to three months.
Estrogen sulphate .s.odium .sa.lt:. :0. .3Ø 6Ø... 9.0 days.
~_ estrone 99 99(50) 99(20). 99(0) %
equilin 100 100(.95) lQ0(~0) 100~50?
equilenin 100 100 100 100 ~-estradiol 100 100 100 100 ~L~&~
The numbers represent the content oE the undecomposed estrogen sulphate sodium salt in the mixtures in percent.
For comparison, the numbers in parentheses represent the values for storage in an exsiccator over potassium hydroxide without the addition of sodium acetate.
Examp e 2 Estrone sulphate sodium salt is stored at 60CC with addition of varying amounts o~ sodium acetate.
Sodium acetate 0 30 days ¢'' ... . _. .... . .. .~
0.5 98 5
2.0 98 98 5.0 98 ~8 The numbers represent the content oE undecomposed estrone sulphate sodium salt in the mixtures in percent.
Claims (3)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Alkali sulphates of natural conjugated estrogens containing sodium acetate as a stabilizing additive in an amount sufficient to stabilize the sulphate against decomposition when stored in the dry state over an extended length of time.
2. Sulphates as claimed in claim 1 containing from 0.5 to 50% by weight of sodium acetate.
3. Sulphates as claimed in claim 1 containing 2 to 10% by weight of sodium acetate.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752546063 DE2546063C2 (en) | 1975-10-10 | 1975-10-10 | Use of sodium acetate as a stabilizer for alkali sulfates of naturally conjugated estrogens |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1064018A true CA1064018A (en) | 1979-10-09 |
Family
ID=5959136
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA263,029A Expired CA1064018A (en) | 1975-10-10 | 1976-10-08 | Stabilizer for natural conjugated estrogens |
Country Status (4)
| Country | Link |
|---|---|
| CA (1) | CA1064018A (en) |
| DE (1) | DE2546063C2 (en) |
| HU (1) | HU172301B (en) |
| NL (1) | NL7611071A (en) |
-
1975
- 1975-10-10 DE DE19752546063 patent/DE2546063C2/en not_active Expired
-
1976
- 1976-10-07 NL NL7611071A patent/NL7611071A/en not_active Application Discontinuation
- 1976-10-08 CA CA263,029A patent/CA1064018A/en not_active Expired
- 1976-10-08 HU HU76SCHE581A patent/HU172301B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE2546063C2 (en) | 1982-12-09 |
| NL7611071A (en) | 1977-04-13 |
| HU172301B (en) | 1978-07-28 |
| DE2546063A1 (en) | 1977-04-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US2238149A (en) | Process for improving the stability of hygroscopic substances | |
| US4113751A (en) | Stabilizer for estrogens | |
| DE69733896T3 (en) | CARBON DIOXIDE ABSORBENT FOR ANESTHESIA | |
| CA1052270A (en) | Oxytetracycline solution for parenteral peroral and local administration and processes for the production thereof | |
| EP1899270A2 (en) | Method for producing an iron sulfate-based phosphate adsorbent | |
| EP1204402B1 (en) | Sulfur adsorbent for reducing onion or garlic breath odor | |
| JPH0347161A (en) | Stable liquid from of 5-aminosalicyclic acid | |
| US3024257A (en) | Stable preparations of alkali metal salts of estrone sulfate | |
| CA2707344C (en) | Stable salts of s-adenosylmethionine and process for the preparation thereof | |
| CA1064018A (en) | Stabilizer for natural conjugated estrogens | |
| DE2042323A1 (en) | Hematopoietic preparation | |
| PT1181248E (en) | Non-caking sodium chloride crystals, a process to make them, and their use in an electrolysis process | |
| US1557266A (en) | Composition adapted to generate free iodine | |
| US5120762A (en) | Method for production of stabilized sodium ascorbate powder | |
| JP5414146B2 (en) | Solid pharmaceutical preparation containing levothyroxine and / or liothyronine salt | |
| SK540290A3 (en) | Parenterally applicable pharmaceutical composition containing bis-indole alkaloid and preparation method thereof | |
| KR19990075100A (en) | Minocycline composition for treatment of periodontitis | |
| US2946796A (en) | Salts of ergot alkaloids | |
| US2768875A (en) | Stabilizing aqueous solutions of polythionates and polythionic acids | |
| US3070503A (en) | Pyrilamine resin absorbate with aspirin and/or ascorbic acid | |
| US6060498A (en) | Composition containing antitumor agent | |
| US3823229A (en) | Inhalation compositions containing 7-(beta-hydroxypropyl)-theophylline | |
| DE2052991A1 (en) | Stabilized aqueous Brenzka techinamin preparation | |
| DE2131616A1 (en) | Pharmaceutical preparation | |
| JP3239079B2 (en) | Cut Flower Life Extension and Cut Flower Life Extension Method |