CA1330297C - Aqueous solution of fat-soluble substance - Google Patents
Aqueous solution of fat-soluble substanceInfo
- Publication number
- CA1330297C CA1330297C CA000588716A CA588716A CA1330297C CA 1330297 C CA1330297 C CA 1330297C CA 000588716 A CA000588716 A CA 000588716A CA 588716 A CA588716 A CA 588716A CA 1330297 C CA1330297 C CA 1330297C
- Authority
- CA
- Canada
- Prior art keywords
- vitamin
- phosphatide
- fat
- soluble substance
- group
- 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 - Fee Related
Links
Classifications
-
- 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
- A61K9/08—Solutions
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
Abstract
ABSTRACT OF THE DISCLOSURE
An aqueous solution is disclosed which comprises a fat-soluble substance, a phosphatide, a polyhydric alcohol and a basic amino acid, a salt thereof or Meglumin.
As a result, uniform emulsification and solubilization for pharmaceutical use are improved.
An aqueous solution is disclosed which comprises a fat-soluble substance, a phosphatide, a polyhydric alcohol and a basic amino acid, a salt thereof or Meglumin.
As a result, uniform emulsification and solubilization for pharmaceutical use are improved.
Description
This invention relates to an aqueous solution of a fat-soluble substance, for example a fat-soluble vitamin, which solution may be uniformly emulsified or solubilized even with only mild stirring.
Hitherto, aqueous solutions of a fat-soluble substance, a phosphatide and a polyhydric alcohol have been obtained using a high pressure homogenizer or an ultrasonic emulsifying machine for an extended time, such as 60 minutes. For this purpose, a strong dispersing power has been required and for this reason mass-production has been impractical.
According to the present invention, there is provided an aqueous solution which comprises a fat-soluble substance, a phosphatide, a polyhydric alcohol and a basic amino acid, a salt thereof or Meglumin.
The present invention also provides a transparent, clear aqueous preparation consisting essentially of a fat-soluble substance selected from the group consisting of vitamin E, vitamin E acetate, coenzyme QlO, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, said fat-soluble substance being emulsified or solubilized in the aqueous phase in the presence of a phosphatide, a polyhydric alcohol and a compound selected from the group consisting of basic amino acids, salts of basic amino acids and N-methyiglucamine, the amount of said compound being from 0.1 to 0.5 parts by weight, per one part by weight of said phosphatide.
In a further aspect the present invention provides a transparent, clear, aqueous preparation consisting essentially of a fat-soluble substance selected from the group consisting of vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, said fat-soluble substance being emulsified or solubilized in the aqueous phase in the presence of a phosphatide selected from the group consisting of soy bean lecithin and egg yolk lecithin, a polyhydric alcohol selected from the group 1~ ' ~''` , ' 1 3302q7 consisting of glycerin and D-sorbitol and a compound selected from the group consisting of L-lysine and L-arginine, the amount of said compound being from 0.1 to 0.5 parts by weight, per one part by weight of said phosphatide, said material being effective to solubilize said fat-soluble substance and said phosphatide, said preparation having a transmittance of light at 640 nm of at least 15%.
In a further aspect the present invention provides a transparent, clear, aqueous preparation consisting essentially of a fat-soluble substance selected from the group consisting of vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, said fat-soluble substance being emulsified or solubilized in the aqueous phase in the presence of N-methylglucamine, a phosphatide selected from the group consisting of soy bean lecithin and -egg yolk lecithin, and a polyhydric alcohol selected from the group consisting of glycerin and D-sorbitol, the amount ~;20 of said N-methylglucamine being from 0.1 to 0.5 parts by weight, per one part by weight of said phosphatide, said N-methylglucamine being effective to solubilize said fat-soluble substance and said phosphatide, said preparation having a transmittance of light at 640 nm of at least 15%.
In practicing the invention, instead of a high power machine, a mild stirring machine, for example a Polytron (trademark) or a homomixer, can be employed, which offers only mild shear stress. Alternatively, an ultra-sonic emulsifying machine can be used for a short time.
This advantageous result is attained as a result of the incorporation of a basic amino acid, a salt thereof or Meglumin into the solution.
It is preferable that the solution contains the fat-soluble substance, the phosphatide, the polyhydric -~35 alcohol, each in a conventional amount, together with from 0.1 to 0.5 part by weight, based on 1 part of the `: A~
,~" ~ . .
1 33~97 phosphatide, of the basic amino acid, salt thereof or Meglumin.
It is also preferred that the basic amino acid is either L-arginine or L-lysine, the fat-soluble substance is selected from vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, the phosphatide is soy bean lecithin or egg yolk lecithin, and the polyhydric alcohol is glycerine or D-sorbitol.
The invention further provides for the pharmaceutical use of the solution as defined above as an injection liquid, an emulsion or an oral liquid preparation.
In the accompanying drawing, Fig. 1 shows graphically the results of Test III below.
The following Examples illustrate the invention.
Example 1 An aqueous solution was prepared in the following way. A solution A comprising 100 mg of vitamin E acetate, 30 mg of L-arginine, 100 mg of purified soy bean lecithin and 770 mg of glycerine was prepared using a Polytron. One gram of the solution A was mixed with 12 ml of purified water, while stirred. A mixture B comprising 0.5 ml of ginseng extract liquid, 25 mg of nicotinic amide, 10 mg. of FMN(VB2), 50 mg. of caffeine, 3000 mg of D-sorbitol, 5000 mg of purified white sugar, 18 mg of benzoic acid, 20 mg of dl-malic acid and a suitable amount of sodium citrate was dissolved in 12 ml of purified water. A mixture D
comprising 3 mg of ethyl paraben, 1 ml of ethanol and a trace of a perfume was added to and mixed with the solution B. The solutions A and B were mixed with each other and the mixture was adjusted with sodium citrate to have a pH
of 5.5. Then further purified water was added thereto to messed up to a total volume of 30 ml. The resultant liquid .~
.;, . .' .
~- A"
;~ - .
,~ .
` 1 3302~7 was found to be transparent and clear, indicating uniform emulsification and solubilization.
Example 2 A mixture B comprising 0.3 g of Meglumin, 6.9 g of glycerine and 0.8 ml of ethanol was heated to obtain a solution. A mixture A comprising 1.0 g of soy bean oil and 1.0 g of soy bean phosphatide was added to the solution B.
A clear solution was obtained with use of a Polytron.
Example 3 3 mg of Meglumin was dissolved in a mixture of 27 mg of glycerine and 50 mg of a 70% solution of D-sorbitol.
10 mg of coenzyme Q and 10 mg of purified egg yolk lecithin were added to the solution. The mixture was treated in a Polytron to form an aqueous solution. The solution was further diluted with water and adjusted with a suitable amount of a solution of citric acid in purified water for the injection to have a pH of about 7 and 1 ml of a clear injection liquid was obtained.
Test I
The aqueous solutions listed in Table 1 were prepared and examined for water dispersibility. Components 1 and 4 were dissolved in water, while heated. Then components 2 and 3 were added to the solution. The mixture was treated in a Polytron at 7000 revolution per minute ~rpm) for 30 minutes. The obtained solutions were observed with respect to their appearance. A 3 percent dispersion of each solution in water was obtained and observed.
Moreover, each was analyzed with respect to transmittance of light at O.D. 640 nm.
,~ :".. ,.:
1 3302q7 Table 1 , composition _ _ component -1 L-arginine - 0.3 g -Meglumin - - 0.3 g 2 soy bean lecithin 1.0 g 1.0 g 1.0 g ~-~
Hitherto, aqueous solutions of a fat-soluble substance, a phosphatide and a polyhydric alcohol have been obtained using a high pressure homogenizer or an ultrasonic emulsifying machine for an extended time, such as 60 minutes. For this purpose, a strong dispersing power has been required and for this reason mass-production has been impractical.
According to the present invention, there is provided an aqueous solution which comprises a fat-soluble substance, a phosphatide, a polyhydric alcohol and a basic amino acid, a salt thereof or Meglumin.
The present invention also provides a transparent, clear aqueous preparation consisting essentially of a fat-soluble substance selected from the group consisting of vitamin E, vitamin E acetate, coenzyme QlO, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, said fat-soluble substance being emulsified or solubilized in the aqueous phase in the presence of a phosphatide, a polyhydric alcohol and a compound selected from the group consisting of basic amino acids, salts of basic amino acids and N-methyiglucamine, the amount of said compound being from 0.1 to 0.5 parts by weight, per one part by weight of said phosphatide.
In a further aspect the present invention provides a transparent, clear, aqueous preparation consisting essentially of a fat-soluble substance selected from the group consisting of vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, said fat-soluble substance being emulsified or solubilized in the aqueous phase in the presence of a phosphatide selected from the group consisting of soy bean lecithin and egg yolk lecithin, a polyhydric alcohol selected from the group 1~ ' ~''` , ' 1 3302q7 consisting of glycerin and D-sorbitol and a compound selected from the group consisting of L-lysine and L-arginine, the amount of said compound being from 0.1 to 0.5 parts by weight, per one part by weight of said phosphatide, said material being effective to solubilize said fat-soluble substance and said phosphatide, said preparation having a transmittance of light at 640 nm of at least 15%.
In a further aspect the present invention provides a transparent, clear, aqueous preparation consisting essentially of a fat-soluble substance selected from the group consisting of vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, said fat-soluble substance being emulsified or solubilized in the aqueous phase in the presence of N-methylglucamine, a phosphatide selected from the group consisting of soy bean lecithin and -egg yolk lecithin, and a polyhydric alcohol selected from the group consisting of glycerin and D-sorbitol, the amount ~;20 of said N-methylglucamine being from 0.1 to 0.5 parts by weight, per one part by weight of said phosphatide, said N-methylglucamine being effective to solubilize said fat-soluble substance and said phosphatide, said preparation having a transmittance of light at 640 nm of at least 15%.
In practicing the invention, instead of a high power machine, a mild stirring machine, for example a Polytron (trademark) or a homomixer, can be employed, which offers only mild shear stress. Alternatively, an ultra-sonic emulsifying machine can be used for a short time.
This advantageous result is attained as a result of the incorporation of a basic amino acid, a salt thereof or Meglumin into the solution.
It is preferable that the solution contains the fat-soluble substance, the phosphatide, the polyhydric -~35 alcohol, each in a conventional amount, together with from 0.1 to 0.5 part by weight, based on 1 part of the `: A~
,~" ~ . .
1 33~97 phosphatide, of the basic amino acid, salt thereof or Meglumin.
It is also preferred that the basic amino acid is either L-arginine or L-lysine, the fat-soluble substance is selected from vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, the phosphatide is soy bean lecithin or egg yolk lecithin, and the polyhydric alcohol is glycerine or D-sorbitol.
The invention further provides for the pharmaceutical use of the solution as defined above as an injection liquid, an emulsion or an oral liquid preparation.
In the accompanying drawing, Fig. 1 shows graphically the results of Test III below.
The following Examples illustrate the invention.
Example 1 An aqueous solution was prepared in the following way. A solution A comprising 100 mg of vitamin E acetate, 30 mg of L-arginine, 100 mg of purified soy bean lecithin and 770 mg of glycerine was prepared using a Polytron. One gram of the solution A was mixed with 12 ml of purified water, while stirred. A mixture B comprising 0.5 ml of ginseng extract liquid, 25 mg of nicotinic amide, 10 mg. of FMN(VB2), 50 mg. of caffeine, 3000 mg of D-sorbitol, 5000 mg of purified white sugar, 18 mg of benzoic acid, 20 mg of dl-malic acid and a suitable amount of sodium citrate was dissolved in 12 ml of purified water. A mixture D
comprising 3 mg of ethyl paraben, 1 ml of ethanol and a trace of a perfume was added to and mixed with the solution B. The solutions A and B were mixed with each other and the mixture was adjusted with sodium citrate to have a pH
of 5.5. Then further purified water was added thereto to messed up to a total volume of 30 ml. The resultant liquid .~
.;, . .' .
~- A"
;~ - .
,~ .
` 1 3302~7 was found to be transparent and clear, indicating uniform emulsification and solubilization.
Example 2 A mixture B comprising 0.3 g of Meglumin, 6.9 g of glycerine and 0.8 ml of ethanol was heated to obtain a solution. A mixture A comprising 1.0 g of soy bean oil and 1.0 g of soy bean phosphatide was added to the solution B.
A clear solution was obtained with use of a Polytron.
Example 3 3 mg of Meglumin was dissolved in a mixture of 27 mg of glycerine and 50 mg of a 70% solution of D-sorbitol.
10 mg of coenzyme Q and 10 mg of purified egg yolk lecithin were added to the solution. The mixture was treated in a Polytron to form an aqueous solution. The solution was further diluted with water and adjusted with a suitable amount of a solution of citric acid in purified water for the injection to have a pH of about 7 and 1 ml of a clear injection liquid was obtained.
Test I
The aqueous solutions listed in Table 1 were prepared and examined for water dispersibility. Components 1 and 4 were dissolved in water, while heated. Then components 2 and 3 were added to the solution. The mixture was treated in a Polytron at 7000 revolution per minute ~rpm) for 30 minutes. The obtained solutions were observed with respect to their appearance. A 3 percent dispersion of each solution in water was obtained and observed.
Moreover, each was analyzed with respect to transmittance of light at O.D. 640 nm.
,~ :".. ,.:
1 3302q7 Table 1 , composition _ _ component -1 L-arginine - 0.3 g -Meglumin - - 0.3 g 2 soy bean lecithin 1.0 g 1.0 g 1.0 g ~-~
3 vitamin E acetate 1.0 g 1.0 g 1.0 g ;~
4 glycerine 8.0 g 7.7 g 7.7 g appearance milky clear clear dispersibility in water milky clear clear -. , , .
transmittance at 640 nm separates over 30% ~ .
over 20%
.. _ .. _. _.. ........ _ _. . . _ __ . . . I
2C Composition 1 is the control and compositions 2 and 3 fall within the invention. Composition 1 was found to have oil and lecithin drops floating on the surface.
Test II
Aqueous solutions were prepared as listed in Table 2, with varying amounts of L-arginine. They were tested with respect to water dispersibility. Results are shown in Table 2. L-arginine was dissolved in glycerine with heating. Then soy bean lecithin and vitamin E acetate were added to the solution and the mixture was treated in a Polytron at 7000 revolutions per minutes for 30 minutes.
They were observed in appearance. A 3% aqueous solution of each resultant was determined in view of transmittance of ~ light at O.D. 640 nm.
`~
A
1 3302q7 Table 2 Composition 0/lo 0.5/10 1/10 2/10 3/10 5/10 L-arginine o 0.05 0.1 0.2 0.3 0.5 5 soy bean lecithin 1 1 1 1 1 1 ;~
vitamin E
acetate 1 1 1 1 1 1 glycerine 8 7.95 7.9 7.8 7.7 7.5 10 appearance milky clear clear clear clear clear transmittance at 640 nm (%) - 10 15 20 30 40 ,.
Ratios in the uppermost column show those of L-arginine to lecithin. In the transmittance test on the 0/10 composition, some oil was found to separate out.
Test III
Aqueous solutions were prepared with varying amounts of L-arginine to soy bean lecithin. L-arginine was dissolved with heating in glycerine. Soy bean lecithin and vitamin E acetate were then added to the solution and the mixture was stirred with an ultra-sonic emulsifying machine for 90 seconds. The obtained aqueous liquids was determined to have a concentration of 3 percent by weight.
They were tested for light transparency at O.D. 640 nm.
The results shown in Fig. 1 reveal that the addition of L-arginine was advantageous in comparison with no addition.
~.
' .'' ','' ::; . . :. ~: .
A
transmittance at 640 nm separates over 30% ~ .
over 20%
.. _ .. _. _.. ........ _ _. . . _ __ . . . I
2C Composition 1 is the control and compositions 2 and 3 fall within the invention. Composition 1 was found to have oil and lecithin drops floating on the surface.
Test II
Aqueous solutions were prepared as listed in Table 2, with varying amounts of L-arginine. They were tested with respect to water dispersibility. Results are shown in Table 2. L-arginine was dissolved in glycerine with heating. Then soy bean lecithin and vitamin E acetate were added to the solution and the mixture was treated in a Polytron at 7000 revolutions per minutes for 30 minutes.
They were observed in appearance. A 3% aqueous solution of each resultant was determined in view of transmittance of ~ light at O.D. 640 nm.
`~
A
1 3302q7 Table 2 Composition 0/lo 0.5/10 1/10 2/10 3/10 5/10 L-arginine o 0.05 0.1 0.2 0.3 0.5 5 soy bean lecithin 1 1 1 1 1 1 ;~
vitamin E
acetate 1 1 1 1 1 1 glycerine 8 7.95 7.9 7.8 7.7 7.5 10 appearance milky clear clear clear clear clear transmittance at 640 nm (%) - 10 15 20 30 40 ,.
Ratios in the uppermost column show those of L-arginine to lecithin. In the transmittance test on the 0/10 composition, some oil was found to separate out.
Test III
Aqueous solutions were prepared with varying amounts of L-arginine to soy bean lecithin. L-arginine was dissolved with heating in glycerine. Soy bean lecithin and vitamin E acetate were then added to the solution and the mixture was stirred with an ultra-sonic emulsifying machine for 90 seconds. The obtained aqueous liquids was determined to have a concentration of 3 percent by weight.
They were tested for light transparency at O.D. 640 nm.
The results shown in Fig. 1 reveal that the addition of L-arginine was advantageous in comparison with no addition.
~.
' .'' ','' ::; . . :. ~: .
A
Claims (15)
1. An aqueous solution which comprises a fat-soluble substance, a phosphatide, a polyhydric alcohol and a basic amino acid, a salt thereof or Meglumin.
2. A solution as claimed in claim 1, wherein the fat-soluble substance, the phosphatide, the polyhydric alcohol, are each present in a conventional amount, and the solution contains from 0.1 to 0.5 part by weight, based on 1 part of the phosphatide, of the basic amino acid, salt thereof or Meglumin.
3. A solution as claimed in claim 1, in which the basic amino acid is L-arginine.
4. A solution as claimed in claim 1, 2 or 3, in which the fat-soluble substance is selected from vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils.
5. A solution as claimed in claim 1, 2 or 3, in which the phosphatide is soy bean lecithin or egg yolk lecithin.
6. A solution as claimed in claim 1, 2, or 3, in which the polyhydric alcohol is glycerine or D-sorbitol.
7. Use of the solution as defined in claim 1, 2, or 3, as an injection liquid, an emulsion or an oral liquid preparation.
8. A transparent, clear aqueous preparation consisting essentially of a fat-soluble substance selected from the group consisting of vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, said fat-soluble substance being emulsified or solubilized in the aqueous phase in the presence of a phosphatide, a polyhydric alcohol and a compound selected from the group consisting of basic amino acids, salts of basic amino acids and N-methylglucamine, the amount of said compound being from 0.1 to 0.5 parts by weight, per one part by weight of said phosphatide.
9. A transparent, clear, aqueous preparation consisting essentially of a fat-soluble substance selected from the group consisting of vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, said fat-soluble substance being emulsified or solubilized in the aqueous phase in the presence of a phosphatide selected from the group consisting of soy bean lecithin and egg yolk lecithin, a polyhydric alcohol selected from the group consisting of glycerin and D-sorbitol and a compound selected from the group consisting of L-lysine and L-arginine, the amount of said compound being from 0.1 to 0.5 parts by weight, per one part by weight of said phosphatide, said material being effective to solubilize said fat-soluble substance and said phosphatide, said preparation having a transmittance of light at 640 nm of at least 15%.
10. A preparation as claimed in claim 8, in which said compound is L-arginine.
11. A preparation as claimed in claim 8, in which said phosphatide is soy bean lecithin or egg yolk lecithin.
12. A preparation as claimed in claim 8, in which said polyhydric alcohol is glycerin or D-sorbitol.
13. A transparent, clear, aqueous preparation consisting essentially of a fat-soluble substance selected from the group consisting of vitamin E, vitamin E acetate, coenzyme Q10, vitamin A, an aliphatic ester of vitamin C, gamma-linolenic acid and vegetable oils, said fat-soluble substance being emulsified or solubilized in the aqueous phase in the presence of N-methylglucamine, a phosphatide selected from the group consisting of soy bean lecithin and egg yolk lecithin, and a polyhydric alcohol selected from the group consisting of glycerin and D-sorbitol, the amount of said N-methylglucamine being from 0.1 to 0.5 parts by weight, per one part by weight of said phosphatide, said N-methylglucamine being effective to solubilize said fat-soluble substance and said phosphatide, said preparation having a transmittance of light at 640 nm of at least 15%.
14. A preparation as claimed in claim 8, wherein said compound is selected from the group consisting of L-arginine, L-lysine and a salt thereof.
15. A preparation as claimed in claim 8, wherein said compound is N-methylglucamine.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12063/88 | 1988-01-22 | ||
| JP63012063A JP2643217B2 (en) | 1988-01-22 | 1988-01-22 | Aqueous liquid of fat-soluble substance |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1330297C true CA1330297C (en) | 1994-06-21 |
Family
ID=11795143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000588716A Expired - Fee Related CA1330297C (en) | 1988-01-22 | 1989-01-20 | Aqueous solution of fat-soluble substance |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5035895A (en) |
| EP (1) | EP0325244B1 (en) |
| JP (1) | JP2643217B2 (en) |
| KR (1) | KR910001923B1 (en) |
| AT (1) | ATE74519T1 (en) |
| CA (1) | CA1330297C (en) |
| DE (1) | DE68901140D1 (en) |
| ES (1) | ES2030915T3 (en) |
| PH (1) | PH26537A (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1250672B (en) * | 1991-07-11 | 1995-04-21 | Idb Holding Spa | ORAL FORMULATIONS OF UBIDECARENONE IN AQUEOUS SOLUTION |
| ES2051643B1 (en) * | 1992-10-13 | 1995-02-16 | Inverni Della Beffa Farma | ORAL FORMULATIONS OF UBIDECARENONE IN THE FORM OF AQUEOUS SOLUTIONS. |
| SI9300468A (en) * | 1992-10-14 | 1994-06-30 | Hoffmann La Roche | Injectable composition for the sustained release of biologically active compounds |
| GR1001364B (en) * | 1992-10-16 | 1993-10-29 | Inverni Della Beffa Farma | Ubidecarenone oral formulations in the form of aqueous solutions. |
| JPH06157294A (en) * | 1992-11-19 | 1994-06-03 | Tanabe Seiyaku Co Ltd | Fine-granular fat preparation |
| DE19647352C2 (en) * | 1996-11-15 | 2000-06-29 | Aqua Nova Getraenketechnologie | Non-alcoholic beverage containing Q 10 |
| IT1304406B1 (en) * | 1998-10-21 | 2001-03-19 | Danital Italia S R L | PREPARATION FOR THE VEHICULATION OF ACTIVE INGREDIENTS BASED ON POLYUNSATURATED ACIDIGIDS OF THE OMEGA GROUP 3. |
| US6087393A (en) * | 1999-06-10 | 2000-07-11 | Igen, Inc. | Stabilized vitamin C formulations |
| DE19944137A1 (en) * | 1999-09-15 | 2001-03-22 | Beiersdorf Ag | O / W emulsions containing one or more biochinones and increased glycerin content |
| US8512718B2 (en) | 2000-07-03 | 2013-08-20 | Foamix Ltd. | Pharmaceutical composition for topical application |
| AU2003261218A1 (en) * | 2002-07-23 | 2004-02-25 | Solae, Llc | Process for removing sugar and/or oil from lecithin |
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Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3962416A (en) * | 1971-01-25 | 1976-06-08 | Sol Katzen | Preserved nutrients and products |
| JPS55127318A (en) * | 1979-03-24 | 1980-10-02 | Rowaale Keshohin Kk | Emulsifier composition |
| DE3224619A1 (en) * | 1981-07-14 | 1983-05-19 | Freund Industrial Co., Ltd., Tokyo | Oral pharmaceutical composition |
| JPS5948414A (en) * | 1982-09-10 | 1984-03-19 | Asahi Denka Kogyo Kk | Water-soluble preparation of vitamin e |
| JPS59193814A (en) * | 1983-04-20 | 1984-11-02 | Ajinomoto Co Inc | Fat emulsion containing amino acid |
| JPS6025918A (en) * | 1983-07-25 | 1985-02-08 | Ajinomoto Co Inc | Aqueous solution containing fat-soluble drug |
| JPS6058915A (en) * | 1983-09-12 | 1985-04-05 | Fujisawa Pharmaceut Co Ltd | Lipid microcapsule preparation containing medicament |
| US4744989A (en) * | 1984-02-08 | 1988-05-17 | E. R. Squibb & Sons, Inc. | Method of preparing liposomes and products produced thereby |
| US4830858A (en) * | 1985-02-11 | 1989-05-16 | E. R. Squibb & Sons, Inc. | Spray-drying method for preparing liposomes and products produced thereby |
| IL78930A0 (en) * | 1985-07-29 | 1986-09-30 | Abbott Lab | Lyophilized emulsion compositions for parenteral administration |
| US4816247A (en) * | 1985-09-11 | 1989-03-28 | American Cyanamid Company | Emulsion compositions for administration of sparingly water soluble ionizable hydrophobic drugs |
-
1988
- 1988-01-22 JP JP63012063A patent/JP2643217B2/en not_active Expired - Fee Related
-
1989
- 1989-01-18 KR KR1019890000485A patent/KR910001923B1/en not_active IP Right Cessation
- 1989-01-18 PH PH38063A patent/PH26537A/en unknown
- 1989-01-19 AT AT89100869T patent/ATE74519T1/en not_active IP Right Cessation
- 1989-01-19 EP EP89100869A patent/EP0325244B1/en not_active Expired - Lifetime
- 1989-01-19 DE DE8989100869T patent/DE68901140D1/en not_active Expired - Fee Related
- 1989-01-19 ES ES198989100869T patent/ES2030915T3/en not_active Expired - Lifetime
- 1989-01-20 CA CA000588716A patent/CA1330297C/en not_active Expired - Fee Related
- 1989-01-20 US US07/300,407 patent/US5035895A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2643217B2 (en) | 1997-08-20 |
| DE68901140D1 (en) | 1992-05-14 |
| EP0325244A1 (en) | 1989-07-26 |
| US5035895A (en) | 1991-07-30 |
| PH26537A (en) | 1992-08-07 |
| KR910001923B1 (en) | 1991-03-30 |
| EP0325244B1 (en) | 1992-04-08 |
| KR890011586A (en) | 1989-08-21 |
| JPH01190629A (en) | 1989-07-31 |
| ATE74519T1 (en) | 1992-04-15 |
| ES2030915T3 (en) | 1992-11-16 |
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