GB2120939A - Aqueous vitamin solutions - Google Patents
Aqueous vitamin solutions Download PDFInfo
- Publication number
- GB2120939A GB2120939A GB08313969A GB8313969A GB2120939A GB 2120939 A GB2120939 A GB 2120939A GB 08313969 A GB08313969 A GB 08313969A GB 8313969 A GB8313969 A GB 8313969A GB 2120939 A GB2120939 A GB 2120939A
- Authority
- GB
- United Kingdom
- Prior art keywords
- hydrosol
- vitamin
- lipophilic
- vitamins
- tenside
- 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.)
- Granted
Links
Classifications
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Stable aqueous solutions contain lipophilic and hydrophilic vitamins in admixture with 4 to 25% (w/v) of one or more polyols and 12 to 30% (w/v) of one or more non-ionic surfactants, based on the total volume of hydrosol, and optionally antioxidants and/or preservatives. The polyol may be glycerin, sorbitol or sucrose. The vitamins may be A, B1, B2, B12, D3, D6, E, K, U, biotin, nicotinamide, folic acid, pantothenol and choline.
Description
SPECIFICATION
Concentrated hydrosols containing lipophilic and hydrophilic vitamins and a process for their preparation
The invention relates to hydrosols containing lipophilic and hydrophilic vitamins and a process for the preparation thereof.
Concentrated vitamin hydrosols are of importance in human and veterinary therapy. They are, for instance, successfully employed in the treatment and prophylaxis of hypovitaminosis on poultry, swine and other mammals.
Concentrated hydrosols containing lipophilic and hydrophilic vitamins are generally difficult to prepare since, in addition to a major amount of lipophilic vitamins A, D and E and occasionally beta-carotene, about 5 to 10 kinds of hydrophilic vitamins are to be solubilized.
The number of publications dealing with this problem is surprisingly low. C. Coles and D. Thomas (J.
Pharm. Pharmacol4,898/1952/)and R. Hüttenrauch and L. Klotz(Arch. Pharm.296, 145)1963/) merely aimed at the solubilization of vitamin A. They conclude that the amount of detergent necessary for solubilization can be reduced to about half by the use of glycerin, sorbitol and saccharose. The authors never investigated the simultaneous solubilization of lipophilic and hydrophilic vitamins, and accordingly, the cited articles contain neither teaching nor hint how to solve this problem.
United States Patent Specification 2,417,299 also relates to the preparation of aqueous solutions of lipophilic vitamins, in particular vitamins A and D, in the presence of glycerin and non-ionic tenside. The solution obtained contains, however, the active ingredients in an amount of at most 10 000 USP units. This method is not suitable for providing the high concentrations which would meet the recent demands.
The object of the present invention is to provide more concentrated hydrosols containing both lipophilic and hydrophilic vitamins. The invention further relates to a process by which said concentrated hydrosols can be prepared.
Our experimental results have shown that when a mixture of lipophilic vitamins is solubilized with polyoxyethylene sorbitan oleate (Tween 80), the non-ionic tenside was required in a relatively large amount (about 20 to 30 times of the lipophilic vitamin mixture) to give a clear solution (hydrosol). the hydrosol was, however, unstable and became cloudy upon the slightest change in the temperature or as a result of a mechanical effect. We have surprisingly found however that the amount of tenside needed can successfully be reduced by adding polyols to the system. Polyol compounds which may be used are desirably those in which each methyl group is bound to an alcoholic hydroxy e.g. glycerin, sorbitol or saccharose can be used.
The effect of the co-solubilizators (polyols) can be explained by the direct influence of the micelle formation.
The polyols are incorporated into the laminar of sferoidal micelles via hydrogen bridges and hence improve their stability.
Accordingly, we provide a concentrated, stable hydrosol containing lipophilic and hydrophilic vitamins in admixture with one or more tensides wherein from 12 to 30% (w/v) of one or more tensides, and from 4 to 25% (w/v) of one or more polyols, based on the total volume of hydrosol, are present. Antioxidants and/or preservatives may also be present.
The invention further relates to a process for the preparation of a concentrated, stable hydrosol containing lipophilic and hydrophilic vitamins in admixture with tensides, and optionally antioxidants and/or preservatives, which comprises dissolving said lipophilic and hydrophilic vitamins in the presence of 4 to 25% (w/v) of one or more polyols and 12 to 30% (w/v) of one or more tensides, based on the total volume of hydrosol, and optionally converting the solution obtained into a conventional pharmaceutical formulation in a manner known per se.
Generally speaking it is preferred that the amounts of tenside and polyol present correspond to a tenside/polyol ratio of from 1: 0.5 to 1: 7.5 when the total vitamin is, for example, 2.0 + 0.5 9./100 ml of solution (1 500 000 IU).
Compositions which contain a mixture of vitamins A, D3 and E will generally contain 0.8 to 1.25 g., preferably 1.1 g. of Tween 80, based on a total vitamin concentration of 100 000 IU (international units).
The solutions containing a combination of lipophilic and hydrophilic vitamins are stable under slightly acidic condition (pH = 3-6, preferably 4-5.5).
Oxidation is generally inhibited by antioxidants conventionally used in the food industry, which have a suitable redox potential, e. g. butylhydroxytoluene, butylhydroxyanisole, nor-dihydroguaiaretic acid, propylgallate, etc. or a mixture thereof with oxycarboxylic acids, e. g. citric acid. The antioxidants are generally employed in an amount of 0.005 to 0.05%, preferably 0.01%.
The hydrosols are generally preserved by preserving agents conventionally used in human preparations, such as with propyl and methyl paraoxybenzoate, a mixture thereof or sodium benzoate.
To increase the stability of the solutions, nitrogen or argon gas may also be employed when preparing the formulations.
The concentrated hydrosols according to the invention have been found superior to other vitamin mixtures, since the lipophilic vitamins can be resorbed from an aqueous solution more rapidly and completely. The stability of the lipophilicvitamins solubilized in an aqueous solution is better than in an oily solution, both at room temperature and at elevated temperatures.
By the co-solubilization technique according to the invention oral and parenteral concentrated polyvitamin formulations can equally be prepared. Before human application, in particular when administered parenterally, the compositions should be diluted to the necessary extent.
The possibility of prepararing concentrated solutions is a further advantage of the invention since there is no need to store and transport high solvent volumes. This is especially advantageous in veterinary therapy, where of the concentrated solutions containing lipophilic and hydrophilic vitamins, depending on the animals treated, very small amounts, generally 0.2-20 ml. per day, are required.
The invention will further be illustrated by the following Examples, which are, however, not intended to limit the scope of the invention.
Example 1
Vitamin A 400 000 IU Vitamin B1 0.14 g.
Vitamin B2 0.21 g.
Vitamin D6 0.14 g.
Vitamin B12 0.0014 g.
Vitamin D3 140 000 IU
Vitamin E 1050 IU
Biotin (vitamin H) 0.0035 g.
Vitamin K 0.0175 g.
Nicotinic acid amide 1.4 g.
Folic acid 0.0175 g.
Sodium bicarbonate 0.007 g.
Coline chloride (2-hydroxy-N,N,N-trimethyiethanaminium hydroxide) 14.0 g.
Panthenol [(R)-2,4-dihydroxy-N-(3-hydroxypropyl)- 3,3-dimethylbutanamidel 0.655 g.
Carotene 0.001 g.
Butylhydroxytoluene 0.01 g.
Citric acid 0.625 g.
Nipasol (4-hydroxybenzoic acid propyl ester) 0.01 g.
Nipagin (4-hydroxybenzoic acid methyl ester) 0.1 g.
Tween 80 17.5 g.
Glycerine 17.5 g.
Distilled water ad 100.0 ml.
Butylhydroxytoluene and the -carotene suspension are dissolved in the lipophilic vitamin mixture, whereupon Tween 80 and glycerine are added with stirring. In a small portion of the distilled water
Nipa-esters are dissolved with boiling, followed by the dissolution of riboflavine-5-phosphate sodium salt, biotin, folic acid and sodium bicarbonate in the hot solution. The solution is then cooled to 40 "C and the remaining ingredients are dissolved. The two solutions are admixed under vigorous stirring and are made up to the final volume with distilled water. A clear solution is obtained, which is filtered and filled into flasks or plastic containers, under inert gas atmosphere. The solutions are preferably kept cool, in darkness. The hydrosol is stable even after a 6-month storage; the active ingredient concentration decreases by 0.5 to 2.5%.
Comparative Example
The composition described in Example 1 was prepared, except that the amount of glycerine was adjusted to 30 % by weight (corresponding to Example 5 of the United States Patent Specification No. 2,417,299).
There could not be obtained a clear, stable solution even by variation of the quality and amount of the tenside.
Example 2
Following the procedure described in Example 1 but replacing 17.5 g. of glycerine with 8.75 g. of sorbitol a stable hydrosol is prepared.
Example 3
Following the procedure described in Example 1 but replacing 17.5 g. of glycerine with 4.375 g. of saccharose a stable hydrosol is prepared.
Example 4
Vitamin A 1 050 000 IU
Vitamin B1 0.149.
Vitamin B2 (as riboflavin-5-phosphate) 0.25g.
Vitamin B6 0.21 g.
Vitamin B12 0.0014 g.
Vitamin D3 105 000 IU
Vitamin E 700 IU
Biotin 0.0035 g.
Vitamin U 2.8g.
Nicotinic acid amide 1.4 9.
Panthenol 0.98g.
Coline chloride 14.0g.
Butylhydroxytoluene 0.01 g.
Citric acid 0.625 g.
Nipasol 0.01 g.
Nipagin 0.1 g
Tween 80 17.5g.
Glycerine 17.5g.
Distilled water ad 100.0 ml.
Butylhydroxytoluene is dissolved in the lipophilic vitamin mixture, whereupon Tween 80 and glycerine are added with a stirring. In a small portion of the distilled water the Nipa-esters are dissolved with boiling, and then ribofiavine phosphate sodium salt and biotin are dissolved in the solution, while hot. The solution is cooled to 40 OC and the remaining ingredients are dissolved. The two solutions are admixed under vigorous stirring, and made up to the final volume with distilled water. A clear solution is obtained, which is filtered and filled into flasks or plastic containers under inert gas atmosphere. The solutions are preferably kept cool, in darkness.
Comparative Example
The composition described in Example 4 above was prepared except that instead of 0.175 parts by weight of glycerine and Tween, respectively the following quantities were used:
a) glycerine 0.10 parts by weight
Tween 80 0.35 parts by weight
b) glycerine 0.10 parts by weight
Tween 80 0.10 parts by weight
c) glycerine 0.12 parts byweight
Tween 80 0.11 parts by weight
There could not be obtained a clear, stable hydrosol in any of these cases.
Example 5
The procedure described in Example 4 is followed, except that 17.5 g. of glycerine are replaced by 8.75 g.
of sorbitol.
Example 6
The procedure described in Example 4 is followed except that 17.5 g. of glycerine are replaced by 4.375 g.
of saccharose.
Claims (11)
1. A concentrated, stable hydrosol containing lipophilic and hydrophilic vitamins in admixture with one or more tensides, wherein from 12 to 30% (w/v) of one or more tensides, and from 4 to 25% (w/v) of one or more polyols based on the total volume of hydrosol are present.
2. A hydrosol as claimed in claim 1 wherein the polyol is glycerin, sorbitol or saccharose.
3. A hydrosol as claimed in claim 1 or claim 2 wherein the tenside is a non-ionic tenside.
4. A hydrosol as claimed in claim 3 wherein the tenside is a polyethylene glycol sorbitan fatty acid ester.
5. A hydrosol as claimed in any of claims 1 to 4 wherein there are from 1:0.5 to from 1:7.5 parts of tenside : polyol when the vitamin concentration is 2.0 + 0.5 g/100 ml of solution.
6. A hydrosol as claimed in any of claims 1 to 5 wherein an antioxidant and preservative are present.
7. A hydrosol as claimed in claim 1 substantially as hereinbefore described.
8. A hydrosol substantially as herein before described with reference to the Examples.
9. A process for the preparation of a concentrated stable hydrosol containing lipophilic and hydrophilic vitamins in admixture with tensides, and optionally antioxidants and/or preservatives, which comprises dissolving the lipophilic and hydrophilic vitamins in the presence of 4 to 25% (w/v) of one or more polyols and 12 to 30% (w/v) of one or more tensides, based on the total volume of hydrosol and optionally converting the solution obtained into a pharmaceutical formulation in a manner knonwperse.
10. A process as claimed in claim 9 substantially as hereinbefore described.
11. A process as claimed in claim 9 substantially as hereinbefore described with reference to the
Examples.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HU163282A HU185533B (en) | 1982-05-21 | 1982-05-21 | Process for producing concentrated hydrosoles containing h lipophilic and hydrophilic vitamines |
Publications (3)
Publication Number | Publication Date |
---|---|
GB8313969D0 GB8313969D0 (en) | 1983-06-29 |
GB2120939A true GB2120939A (en) | 1983-12-14 |
GB2120939B GB2120939B (en) | 1986-01-22 |
Family
ID=10955423
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB08313969A Expired GB2120939B (en) | 1982-05-21 | 1983-05-20 | Aqueous vitamin solutions |
Country Status (8)
Country | Link |
---|---|
AT (1) | AT384548B (en) |
BE (1) | BE896782A (en) |
CA (1) | CA1204385A (en) |
DD (1) | DD209734A5 (en) |
DE (1) | DE3318513A1 (en) |
GB (1) | GB2120939B (en) |
HU (1) | HU185533B (en) |
SU (1) | SU1220562A3 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5767123A (en) * | 1994-11-17 | 1998-06-16 | Tanabe Seiyaku Co., Ltd. | Total parenteral nutrition solution containing water-soluble vitamin B |
EP0674505B2 (en) † | 1992-12-18 | 2009-08-12 | Beiersdorf Aktiengesellschaft | Synergistic combinations of active substance for the cosmetic or dermatological care of the skin, hair and nails |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB946086A (en) * | 1960-09-19 | 1964-01-08 | Merck & Co Inc | Parenteral aqueous solutions of fat-soluble vitamins |
GB1041890A (en) * | 1963-11-01 | 1966-09-07 | Hoffmann La Roche | Novel lipophilic preparations and the manufacture thereof |
GB1300345A (en) * | 1970-03-17 | 1972-12-20 | Merck & Co Inc | Solubilized liquid preparations |
GB1362719A (en) * | 1970-10-15 | 1974-08-07 | Hoechst Ag | Medicinal preparation and process for preparing it |
GB1471797A (en) * | 1975-02-14 | 1977-04-27 | Hoffmann La Roche | Vitamin preparations |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DD27938A (en) * | ||||
DD36799A (en) * | ||||
US2417299A (en) * | 1943-08-06 | 1947-03-11 | Us Vitamin Corp | Fat-soluble vitamin solutions |
US2907696A (en) * | 1956-01-03 | 1959-10-06 | Pfizer & Co C | Stable vitamin a for aqueous dispersions |
FR1372408A (en) * | 1960-06-15 | 1964-09-18 | Ile De Rech S Scient Et Ind So | Manufacturing process for aqueous polyvitamin solutions and emulsions stable in air and in light |
-
1982
- 1982-05-21 HU HU163282A patent/HU185533B/en unknown
-
1983
- 1983-05-06 CA CA000427679A patent/CA1204385A/en not_active Expired
- 1983-05-19 BE BE0/210801A patent/BE896782A/en not_active IP Right Cessation
- 1983-05-20 SU SU833599272A patent/SU1220562A3/en active
- 1983-05-20 DE DE19833318513 patent/DE3318513A1/en active Granted
- 1983-05-20 GB GB08313969A patent/GB2120939B/en not_active Expired
- 1983-05-20 AT AT185783A patent/AT384548B/en not_active IP Right Cessation
- 1983-05-20 DD DD25113883A patent/DD209734A5/en not_active IP Right Cessation
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB946086A (en) * | 1960-09-19 | 1964-01-08 | Merck & Co Inc | Parenteral aqueous solutions of fat-soluble vitamins |
GB1041890A (en) * | 1963-11-01 | 1966-09-07 | Hoffmann La Roche | Novel lipophilic preparations and the manufacture thereof |
GB1300345A (en) * | 1970-03-17 | 1972-12-20 | Merck & Co Inc | Solubilized liquid preparations |
GB1362719A (en) * | 1970-10-15 | 1974-08-07 | Hoechst Ag | Medicinal preparation and process for preparing it |
GB1471797A (en) * | 1975-02-14 | 1977-04-27 | Hoffmann La Roche | Vitamin preparations |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0674505B2 (en) † | 1992-12-18 | 2009-08-12 | Beiersdorf Aktiengesellschaft | Synergistic combinations of active substance for the cosmetic or dermatological care of the skin, hair and nails |
US5767123A (en) * | 1994-11-17 | 1998-06-16 | Tanabe Seiyaku Co., Ltd. | Total parenteral nutrition solution containing water-soluble vitamin B |
Also Published As
Publication number | Publication date |
---|---|
HU185533B (en) | 1985-02-28 |
ATA185783A (en) | 1987-05-15 |
BE896782A (en) | 1983-09-16 |
DD209734A5 (en) | 1984-05-23 |
SU1220562A3 (en) | 1986-03-23 |
GB8313969D0 (en) | 1983-06-29 |
GB2120939B (en) | 1986-01-22 |
DE3318513C2 (en) | 1993-07-01 |
DE3318513A1 (en) | 1983-11-24 |
CA1204385A (en) | 1986-05-13 |
AT384548B (en) | 1987-11-25 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19960520 |