|Publication number||US3914419 A|
|Publication date||Oct 21, 1975|
|Filing date||Jan 10, 1975|
|Priority date||Aug 2, 1973|
|Publication number||US 3914419 A, US 3914419A, US-A-3914419, US3914419 A, US3914419A|
|Inventors||Haeger Bruce Edwin, Nash Robert Arnold|
|Original Assignee||American Cyanamid Co|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (10), Referenced by (20), Classifications (12)|
|External Links: USPTO, USPTO Assignment, Espacenet|
United States Patent [1 1 Haeger et a1.
[4 1 Oct. 21, 1975 Mills; Robert Arnold Nash, Spring Valley, both of NY.
 Assignee: American Cyanamid Company,
 Filed: Jan. 10, 1975  Appl. No.: 540,060
Related US. Application Data  Continuation-in-part of Ser. No. 384,995, Aug. 2,
 References Cited UNITED STATES PATENTS 10/1957 Aterno et a1 424/344 2/1'958 Newark et a1. 424/201 Conine et al. 424/280 2,846,352 8/1958 Bryant 424/280 2,914,446 11/1959 MacDonald 424/280 2,939,821 6/1960 Freedman et al..... 424/280 2,939,829 6/1960 Gerber et al 424/280 2,959,520 11/1960 Kawasiri 424/255 3,168,440 2/1965 Meyer 424/104 3,626,065 12/1971 Maerawa et a1. 424/280 Primary ExaminerNorman A. Drezin Attorney, Agent, or FirmSamuel Branch Walker  ABSTRACT A stable liquid multivitamin preparation in injectable form contains thiamine (B riboflavin (B niacinamide, pyridoxine (B B (cyanocobalamin), and 0ptionally biotin and dexpanthenol in one phase at pH 4.5 to 5.5; and in a second phase, at pH 6.8 to 7.6, sodium ascorbate (C), folic acid, and niacinamide, and optionally Vitamins A, D and E so that storage incompatible vitamin components are held in separate compartments of a syringe, in separate phases, for consecutive administration from a two compartment syringe; thereby minimizing loss of potency on storage.
5 Claims, 3 Drawing Figures us. Patent 0ct.2 1,1975 3,914,419
TWO COMPARTMENT ONE UNIT CONSECUTIVELY INJECTABLE LIQUID VITAMIN PACKAGE This application is a continuation-in-part of copending application Ser. No. 384,995, filed Aug. 2, 1973, and now abandoned.
BACKGROUND OF THE INVENTION This invention is concerned with an improved injectable multivitamin package having two storage incompatible liquid mixtures of vitamins separately maintained in sterile injectable condition and capable of being administered consecutively by intramuscular injection. The mixture may also be injected through a rubber stopper into an intravenous feeding bottle without compromising sterility.
Prior to the development of this invention, the commercial means of providing a mixture of vitamins A, B,, 8,, and C and others in an injectable form was to prepare certain of the vitamins in liquid form while the balance of the vitamins were prepared as a dried powder; or as two liquids in separate packages, usually consisting of an ampul and a vial. Just prior to administration, the powder was dissolved in the liquid and the combination was then injected into the host. This cumbersome method was necessitated by the incompatibility of the various vitamin components. If all of these components were combined in one liquid form, the product would be unstable. If the solution pH of certain of the vitamin components was adjusted to alkaline or acid conditions in order to improve stability, the result was a product which caused irritation at the site of injection, or in which at least some of the vitamins were not storage stable.
Now, for the first time, an injectable multivitamin preparation containing vitamins A, B,, 8, and C and others in liquid form has been developed which is stable, non-initating and which, because of its unique mode of maintenance, provides an easy and safe one step method of administering said vitamins.
The advantage of the two component injectable liquid system within one package unit set forth herein, rather than two package injectable units, offers a great convenience to the administrator and danger of con tamination is practically eliminated. Current packaging of a product of this type consists of a two package unit, i.e., vial and ampul or two vials. One unit requires reconstitution with the other or withdrawal from each prior to administration. This is considered tedious and sometimes a dangerous practice. The latter involves possible contamination of sample when a common needle used to withdraw from one unit is also used to withdraw from the second, and the danger of glass fragments when one package unit consists of an ampul.
U.S. Pat. No. 3,626,065, Maekawa and Egawa, is concerned with a stable aqueous multivitamin preparation in which vitamin B, is isolated from vitamins A and C and nicotinamide. This patent points out that it is known that vitamin B,, vitamin C and vitamin A are unstable together in aqueous multivitamin preparations. U.S. Pat. No. 3,626,065 states that vitamins B, and C are stable against hydrolysis in different pH regions, below pH 4.0 for vitamin B, and pH 5.0 to 7.0 for vitamin C.
The U.S. Pat. No. 3,626,065 notes that, in general, the pH of the aqueous multivitamin preparations on the market is adjusted to stabilize either vitamin B, or C, or alternatively, the pH is maintained at pH 4.0-5.0. These methods are unsatisfactory since the former sacrifices one or more vitamins to a specific vitamin and the latter is only a compromise.
Said U.S. Pat. No. 3,626,065 is concerned with a stable aqueous multivitamin preparation stored in a two compartment bottle-type container wherein the two liquid vitamins, vitamin B, containing and vitamin A, C, and nicotinamide containing, are admixed together before use. According to said U.S. Pat. No. 3,626,065, the pH of the vitamin A, C, and nicotinamide preparation is maintained at about pH 6, and the pH of the vitamin B, preparation below pH 4, at about pH 3.0. Said U.S. Pat. No. 3,626,065 does not disclose consecutive or serial injection of the two separately held vitamin preparations into a host. It is concerned solely with storage and admixture immediately prior to use. Moreover, as will be pointed out herein, the pH of the vitamin B, preparation of the present invention is maintained at a pH above 4 in contrast to the U.S. Pat. No. 3,626,065 disclosure of below pH 4.0 (Col. 1, line 32) and at about pH 3.0 (Col. 4, Line 69).
Numerous patents are concerned with and point up the problem of maintaining stable liquid vitamin preparations, for example, U.S. Pat. Nos. 2,939,821; 2,846,352; 2,939,820; 3,168,440: 2,823,167; 2,835,627; 2,914,446; and 2,959,520. However, no art is known which discloses the claimed aqueous multivitamin package or its claimed method of administration.
SUMMARY OF THE INVENTION The invention here lies in the concept of an injectable, two compartment, one unit, liquid-liquid preparation of vitamins A, 8,, 8, and C and others, maintained separately because of incompatibility and capable of being administered to a host in one step.
Thiamine (B,), riboflavin (B niacinamide, pyridoxine (B 13, (cyanocobalamin), and optionally biotin and dexpanthenol are dissolved in a clear aqueous solution in one phase at a pH of 4.5 to 5.5. In a second phase, at pH 6.8 to 7.6, sodium ascorbate (C), folic acid, and niacinamide, and optionally Vitamins A, D and E are similarly dissolved in a clear aqueous solution. These solutions are consecutively placed, in a conventional manner, in a two compartment syringe, the pH 4.5 to 5.5 phase in one compartment and the pH 6.8 to 7.6 in the other compartment, The purpose of the two compartment syringe is to consecutively, se quentially or serially deliver the two incompatible vita min preparations which have been separated until the moment of administration.
Surprisingly, at these pH values, the cyanocobalamin (8, and the thiamine (B,) are both sufficiently stable for satisfactory shelf life. As taught by Maekawa, et al., the thiamine would be more stable at a more acid pH, but the 13, would be less stable. A small amount of ferrous citrate may be used to control oxidationreduction so as to permit storage stability.
Because vitamins are characteristically very reactive under body conditions, and catalyze reactions in the host, it is to be expected that they can react with each other and other components, so the formulation of compatible storage stable compositions containing as many different vitamins as can be packaged together has been the subject of much research in the industry.
The type of two compartment syringe is not critical so long as it is capable of maintaining the two liquids separately and administering the two liquids consecutively, sequentially or serially. Suitable two compartment syringes are the two compartment syringe with a conventional by-pass valve such as is manufactured by Becton-Dickenson. Another suitable two compartment syringe is that with a separator valve such as those sold by Century Laboratories, Inc., Turnersville, New Jersey.
Two componentsyringes with a by-pass are shown in Brown, US. Pat. No. 2,7l7,60l, Sept. '13, 1955 and Visser, et al., US. Pat. No. 3,330,282, July II, 1967. A valved free piston in a two-compartment syringe is shown by McConnaughey and Cohen, US. Pat. No. 3,091,240, May 28, 1963.
One aspect of the present invention is a stable aqueous multivitamin preparation consisting of two incompatible aqueous vitamin preparations each held in a separate compartment of a two compartment syringe capable of consecutively, or sequentially or serially injecting said preparations into a host, one of which is at a pH of 6.8 to 7.6 containing vitamin A, D, E, C, niacinamide and folic acid; and the other of which is at a pH above 4.5 to 5.5 containing vitamins B,, B B 8, dexpanthenol and niacinamide.
A further aspect of the present invention is the method of administering the above aqueous vitamin preparations to a host serially through a single needle at a single injection.
BRIEF DESCRIPTION OF THE DRAWING The advantages of the invention as well as specific embodiments and use thereof may be seen by referring to the following description and the accompanying drawing, in which:
FIG. 1 is a by-pass type syringe, with the tip cover in place, capable of maintaining, and upon removal of the tip cover and replacement with a needle for injection, administering the aqueous multivitamin preparations according to this invention.
FIG. 2 is a cross-section across 2-2 in FIG. 1 to more clearly show the by-pass aspect of the syringe of FIG. 1.
FIG. 3 is a separator valve type of syringe capable of maintaining and administering the aqueous multivitamin preparations according to this invention, with the tip cover removed and a needle for injection in place.
DESCRIPTION OF THE INVENTION With reference to FIG. 1, the aqueous pH 4.5 to 5.5 (vitamin 8,, B etc.) preparation is placed in lower chamber 1, in a conventional manner, and is separately retained or maintained therein by container wall 15 of syringe l9, tip cap 2 and divider plug 3. The aqueous pH 6.8 to 7.6 (vitamin C, folic acid, etc.) preparation is placed in upper chamber 4, in a conventional manner, and is separately retained or maintained therein by container wall 16 of syringe l9, divider plug 3 and plunger plug 5.
To use the unit shown by FIG. 1, rubber tip cap 2 is removed, a sterile needle for injection is attached, intravenous infusion or intramuscular penetration is made in the host, and as plunger 6 of syringe 19 is activated, the host receives an initial injection of the vitamin B,, B etc. preparation from lower chamber 1 followed, as divider plug 3 reaches by-pass valve 7, by a consecutive or sequential or serial injection of the vitamin C, folic acid etc. preparation from upper chamber 4. In such a manner the host conveniently receives, with a maximum of safety, the entire multivitamin preparation contents of the syringe in one step. The storage-incompatible vitamin components, which cause stability problems, are maintained separately and yet the administration of the total vitamin content can be made without irritation to the host in one easy step, obviating the need for mixing components prior to administration.
The order of the multivitamin preparations can be reversed in the two chambers without departing from the scope of the invention.
By serially injecting, the components are injected into a subject at the time any mixing occurs, or for intravenous feeding, are diluted into the intravenous bottle, so as to minimize intraction. In a package system which requires mixing before administration, there is always a chance that the user will mix the components and keep the mixture an undesirably long time. With sequential injection, this misuse by the ultimate user is prevented.
With reference to FIG. 3, the aqueous pH 4.5 to 5.5 (vitamin 8,, B etc.) preparation is placed in lower chamber 8, in a conventional manner, and is separately retained or maintained therein by container wall 17 of syringe 18, needle 10 and separator valve 9. The aqueous pH 6.8 to 7.6 (vitamin C, folic acid, etc.) preparation is placed in upper chamber 11, in a conventional manner, and is separately retained or maintained therein by container wall 20 of syringe l8, plunger plug 12 and separator valve 9. Separator valve 9 is made of rubber, or the like, with slit l4 centrally located therein which opens under pressure from plunger 13 permitting the contents of upper chamber 11 to pass through slit 14 into lower chamber 8. Slit 14 in separator valve 9 is closed when not under pressure thereby sealing off upper chamber 11 from lower chamber 8.
To use the unit shown in FIG. 3, intravenous infusion or intramuscular penetration is made with needle 10 in the host, and as plunger 13 of syringe 18 is activated, the host receives an initial injection of the vitamin preparation from lower chamber 8 followed, as plunger 13 moves toward the separator valve 9, and as the contents of lower chamber 8 are emptied, by a consecutive, sequential or serial injection of the vitamin preparation from upper chamber 11. Thus, again, in such a manner the host conveniently receives with a maximum of safety, the total multivitamin content of the syringe in one easy step.
Here again, the order of the multivitamin preparations can be reversed in the two chambers.
The concentrations of the vitamins in the two compartments is in part limited by solubility considerations, but is more controlled by therapeutic considerations. In general, two components of one milliliter each can provide the therapeutically preferred dose for most patients. For special deficiencies, either additional components may be added, or the patient treated with massive doses for a particular syndrome but for general usage the following formulation is preferred for a complete multivitamin preparation:
COMPLETE MULTIVITAMIN FORMULA FOR PARENTERAL ADMINISTRATION Per syringe of Phase A l milliliter vitamin A (as palmitate) 2500 l0.000 units vitamin D crystalline 200 500 units vitamin E 3 30 units ascorbic acid USP as sodium salt)(C) 90 500 units folic acid U.S.P. 0.1 l.0 mg. niacinamide U.S.P. 20 35 mg. polysorbate 80 U.S.P. 50 100 mg. benzyl alcohol reagent l5 mg. propylene glycol 50 100 mg. water for injection U.S.P. qs
to pH 6.8 to 7.6 100% Per syringe of Phase 8 l milliliter thiamine (as HCl U.S.P.) (8,) l 10 mg. riboflavin USP(as 5- phosphate, sodium, 70%) (B 1 10 mg. niacinamide U.S.P. 55 65 mg. pyridoxine (as HCl U.S.P.)
(B 1 mg. cyanocobalamin U.S.P. 5 25 mcg. biotin 0 100 mcg. dexpanthenol 0 l0 mg. ferrous citrate reagent 0.046 mg. benzyl alcohol reagent l0 15 mg. water for injection U.S.P.
qs to pH 4.5 to 5.5 100% Benzyl alcohol is present in both components. Its function as a preservative and local anaesthetic is well recognized. The polysorbate 80 and propylene glycol serve to insure solubility of the constituents. Ferrous citrate serves to stabilize the vitamin B Both biotin and dexpanthenol (D-pantothenyl alcohol) may be considered as vitamins, and are advantageously added to insure completeness of the vitamin dosage. Because vitamin deficiencies may be so varied, and because an excess of vitamins are usually so innocuous, it is generally desirable to administer doses large enough to be sure of adequacy, rather than attempt to use minimum dosages.
A similar preparation may be prepared with the B complex, and omitting vitamins A, D, and E:
B COMPLEX Per syringe of Phase A l milliliter ascorbic acid U.S.P.(as
sodium salt) (C) 90 500 mg. folic acid U.S.P. v 0.l 1.0 mg. niacinamide U.S.P. 35 mg. benzyl alcohol reagent l0 15 mg. water for injection U.S.P. qs
to pH 6.8 to 7.6 100% Per syringe of Phase B l milliliter thiamine (as HCl U.S.P.)(B,) l [0 mg. riboflavin USP(as 5'- phosphate, sodium 70%) (B l 10 mg. niacinamideU.S.P. 55 65 mg. pyridoxine (as HCI U.S.P.)
(B 1 l5 mg. cyanocobalamin U.S.P.(B, 5 mcg. biotin 1 O 100 mcg. dexpanthenol 0 l0 mg. ferrous citrate reagent 0.046 mg. benzyl alcohol reagent vl0 l5 mg. water for injection U.S.P.
qs to pH 4.5 to 5.5 I00% In filling these formulations, an overage should be provided. That is, the syringe package should be filled so as to deliver 1 milliliter of each component which, depending on the dead space in the syringe can require from about 1.1 to 1.25 milliliter per component per syringe. Preferably, the solutions are sterilized by sterile filtration techniques, and the syringes are aseptically assembled. Such packaging procedures are conventional in the industry.
The invention is illustrated by the following examples:
balamin, dexpanthenol, and a portion of the total amount of niacinamide (Phase B) are put into aqueous solution sterile filtered and filled aseptically into the lower chamber of a syringe such as shown in FIGS. 1 and 3, in a conventional manner, so as to discharge the above amounts per syringe. The vitamin C, folic acid and the balance of the total amount of niacinamide (Phase A) are put into aqueous solution, sterile filtered and aseptically filled in the upper chamber of a syringe such as shown in FIGS. 1 and 3, in a conventional manner so as to obtain the above amounts per syringe. All filling is done using sterile techniques. The pH of Phase A is a natural pH of from 6.8 to 7.6 and that of Phase B a natural pH of from 4.5 to 5.5.
In detail, Phase A is prepared under an atmosphere of nitrogen. Fresh water for injection representing of the final formulation volume is added to a glass or stainless steel container and brought to 60C. with nitrogen sparging. The sodium ascorbate is added and dissolved. The solution is reduced to room temperature. The folic acid and niacinamide are mixed together using only enough water to produce a heavy, homogeneous slurry. This slurry is added to the bulk solution and dissolved. The benzyl alcohol is added and mixed. The solution is brought to final volume with water for injection and possesses a natural pH of from 6.8 to 7.6. It is sterile filtered through an 0.2um membrane into a sterile container under a nitrogen atmosphere.
Phase B is also prepared under an atmosphere of ni trogen. The niacinamide and riboflavin are dissolved in fresh water for injection representing of the final formulation volume. The thiamine and pyridoxine are added and dissolved. The dexpanthenol is weighed in a container, a small quantity of water is added and the mixture is warmed to 50C. on a steam bath. This mixture is added to the above solution of vitamins. The ferrous citrate is added and dissolved by mixing for 30 minutes. The cyanocobalamin is added and dissolved. The benzyl alcohol is added and mixed for 30 minutes. The solution is brought to volume with water for injection and mixed. This mixture possesses a natural pH of 4.5 to 5.5. it is sterile filtered through a 0.22 um membrane into a sterile container under a nitrogen atmosphere.
EXAMPLE 2 Phase A Per Syringe vitamin A palmitate 10,000 Units vitamin D crystalline 500 Units d-Alpha tocopheryl acetate NF. 30 Units ascorbic acid USP (as sodium salt 300 mg. folic acid U.S.P. 1 mg. niacinamide U.S.P. 20 mg. polysorbate 8O U.S.P. 10% w/v benzyl alcohol a reagent 10 mg. propylene glycol U.S.P. 100 mg. water for injection U.S.P. qs to 1 milliliter Phase B thiamine HCl U.S.P. 10 mg. riboflavin USPtas '-phosphate.
sodium, 70%) (B mg. niacinamide U.S.P. 55 mg. dexpanthenol 10 mg. pyridoxine HCI U.S.P. mg. cyanocobalamin U.S.P. 15 mcg. ferrous citrate reagent 0.046 mg. benzyl alcohol reagent 10 mg. water for injection U.S.P. qs to l milliliter In a conventional manner similar to that of Example 1, Phase A and B are prepared and placed in a syringe such as shown in FIGS. 1 and 3. The pH of Phase A is a natural pH of from 6.8 to 7.6 and that of Phase B 4.5
In detail, Phase A is prepared under an atmosphere of nitrogen. The benzyl alcohol is weighed into a container. The vitamin D is added and dissolved. The vitamin A and d-alpha tocopheryl are added and mixed. The polysorbate 80 is added and the mixture is stirred thoroughly while heating to 50C. on a steam bath. This mixture is added slowly with vigorous stirring to a mixture of propylene glycol and water. The sodium ascorbate is added and dissolved. (If turbidity occurs it will clarify later when brought to volume). The folic acid and niacinamide are mixed together with small increments of water to provide a thin paste. This paste is diluted with additional water and added to the above described vitamin solution. The solution is diluted to volume with water for injection and filtered through a sterile 0.2 pm membrane into a sterile container under a nitrogen atmosphere. The natural pH of this solution is 6.8 to 7.6.
Phase B formulation and preparation are exactly as described under Phase B of Example 1.
Following is a brief description of the filling process. The Phase B component is aseptically filled at 1.15 cc into presterilized and siliconized 3 cc syringes, containing tip caps at the needle end. These syringes are then fitted with a center divider plug (slit type, if the syringe does not contain a by-pass valve, or solid type if a bypass valve is present) by passing several (18) at a time held in a filling rack into a vacuum chamber. A sleeve containing the plugs is placed over the syringe rack and, under vacuum, a bar of insertion fingers displaces the plugs into the syringe barrel to a point slightly above the liquid surface. Vacuum pulls the plugs to or close to the liquid surface. The syringes are then recycled through the filling chamber. The Phase A component is filled at 1.15 cc into the upper chamber. The syringes are vacuum fitted with an upper, threaded plug. (The thread is for plunger rod insertion). The syringes are then removed from sterile conditions and packaged.
The same filling procedure may be conducted without the use of vacuum equipment by employing a hollow needle wire which is placed at the plug edge at the time of plug insertion, allowing the escape of trapped air. The syringes are recycled for the second chamber filling and the needle wire is again used to position the upper plug.
As illustrative of the storage characteristics of the present compositions, solutions were prepared containing:
The solution was separated into seven equal portions of approximately 400 ml each in 500 ml glass stoppered graduated cylinders under nitrogen. The pH of each fraction was adjusted as follows:
Fraction Final pH ingredient Employed A 4.52 none (no adjustment) B 4.0 10.6 ml of 10% HCI C 3.5 26.8 ml of 10% HCl D 3.0 48.8 ml of 10% HO E 4.0 5.1 ml of lactic acid F 3.5 22.7 ml of lactic acid G 3.0 66 ml of lactic acid of physical instability (precipitation, discoloration) prior to determining potency stability through appropriate assay means. Samples from solution D, in syringes and vials, precipitated but were assayed for Vitamins B B B and B nevertheless. The results appear in Tables I, II and III:
Table I Physical Stability in Vials and Syringes Storage Conditions Solutions Adjusted w/HCl Solutions Adjusted w/Lactic Acid Time Temperature A(pH 4.5) M40) C(3.5) D(3.0) E(4.0) F(3.5) G(3.0)
1 Week 42C. D L" LT PPT L D D RT" NC NC NC PPT NC NC NC 3C. NC NC NC PPT NC NC NC 2 Weeks 42C. D L LT PPT D D D RT NC NC NC PPT NC NC NC 3C. NC NC NC PPT NC NC NC 4 Weeks 42C. D L LT PPT D D D RT NC NC NC PPT NC NC NC 3C. NC NC NC PPT NC NC NC 8 Weeks 42C. D L LT PPT D D D RT NC NC NC PPT NC NC i NC 3C. NC NC NC PPT NC NC NC "D dark solution "L lighter solution than D LT lightest solution (lighter than L) PPT precipitate 'RT room temperature NC no change Color fading is a sign of instability. Solution C(pH 3.5) precipitated when ejected from syringes in 8 week room temperature sample, and, hence, was unsatisfactory.
Table II Stability in Vials as Percent of Initial After Storage for 1 Month at 42C.
Vitamin Potency in Solution pH B, B 5 12 A 4.52 9l 102 l02 92 B 4.0 96 102 97 92 C 3.5 99 I02 l05 78 D 3.0 99 98 I 93 E 4.0 92 99 97 91 F 3.5 91 100 103 83 G 3.0 90 103 I 68 Table Ill Stability in Syringes as Percent of Initial After Storage for 4 Month at Room Temperature Vitamin Potency in 7:
Solution pH B, B B B A 4.52 97 101 97 97 B 4.0 98 102 99 96 C 3.5 99 I00 98 93 D 3.0 PPT" PPT PPT PPT E 4.0 97 100 99 95 F 3.5 98 I02 99 86 G 3.0 98 I02 98 76 "PPT precipitate -mins B,, B and B but losses in Vitamin B potency were observed when solutions were adjusted to pH values below 4. This degradation was accelerated by the presence of lactic acid, an organic acidulant.
Even though there is some loss of stability of B at the pH of 4.52, this pH permits stability of Vitamin B The storage-stability of multivitamin preparation must be based on a series of compromises, and the present packages are uniquely satisfactory.
What is claimed:
1. A stable aqueous multivitamin preparation in sterile, storage-stable injectable form in a two compartment hypodermic syringe comprising two incompatible vitamin components each held in a separate compartment of said syringe, one of said components having a pH of 6.8 to 7.6 consisting essentially of:
vitamin A palmitate 0 10.000 units vitamin D 0 500 units vitamin E 0 30 units ascorbic acid 500 mg. folic acid 0.1 l mg., and niacinamide 2O 25 mg.
per milliliter as the vitamin ingredients thereof; in an aqueous carrier; and the other of said components having a pH of 4.5 to 5.5 consisting essentially of:
thiamine hydrochloride 1 10 mg. riboflavin l 10 mg. niacinamide 55 65 mg. pyridoxine hydrochloride 1 l5 mg. cyanocobalamin 5 25 mcg. dexpanthenol 0 10 mg.. and biotin 0 mcg.
per milliliter as the vitamin ingredients thereof, in an aqueous carrier.
2. The preparation of claim 1 in which the component having a pH of 6.8 to 7.6 consists essentially of:
ascorbic acid 90 500 mg. folic acid 0.1 l mg. and niacinamide 20 35 mg.
per milliliter as the vitamin ingredients thereof; in an aqueous carrier.
3. The preparation of claim 1 in which the component having a pH of 6.8 to 7.6 consists essentially of:
vitamin A palmitate 2500 10,000 units vitamin D 200 500 units vitamin E 3 30 units ascorbic acid 90 500 mg. I folic acid 0.1 l Rigahtl niacinamide 20 35 mg.
per milliliter as the vitamin-ingredients thereof; in an aqueous carrier.
4. The preparation of claim 1 in which the component having a pH of 6.8 to 7.6 consists essentially of:
1 mg, and 20 mg.
niacinamide per milliliter as the vitamin ingredients thereof; in an aqueous carrier having -15 mg. of benzyl alcohol therein; and the other of said components having a pH of 4.5 to 5.5 consisting essentially of:
thiamine hydrochloride 10 mg. riboflavin 10 mg. niacinamide 55 mg. dexpanthenol 10 mg. pyridoxine hydrochloride 15 mg. and cyanocobalamin 15 mcg.
per milliliter as the vitamin ingredients thereof, in an aqueous carrier having therein lO-15 mg. of benzyl alcohol and 0.046 mg. of ferrous citrate.
5. The preparation of claim 1 in which the comp0- nent having a pH of 6.8 to 7.6 consists essentially of:
vitamin A palmitate 10,000 units vitamin D 500 units vitamin E 30 units ascorbic acid 300 mg. folic acid 1 mg.v and niacinamide 20 mg.
thiamine hydrochloride 10 mg. riboflavin 10 mg. niacinamide 55 mg. dexpanthenol l0 mg. pyridoxine hydrochloride 15 mg.. and cyanocobalamin 15 mcg.
per milliliter as the vitamin ingredients thereof, in an aqueous carrier having therein 10-15 mg. of benzyl alcohol and 0.046 mg. of ferrous citrate.
l l l
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|CN102068453A *||Sep 7, 2010||May 25, 2011||北京京卫信康医药科技发展有限公司||Stable complex vitamin composite and preparation method thereof|
|EP0072057A1 *||Jul 13, 1982||Feb 16, 1983||Duphar International Research B.V||Automatic injection syringe|
|WO2001070044A1 *||Mar 23, 2001||Sep 27, 2001||Aventis Animal Nutrition S.A.||Liquid vitamin composition|
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|U.S. Classification||514/52, 514/249, 514/168|
|International Classification||A61M5/31, A61K9/00, A61M5/28|
|Cooperative Classification||A61M2005/1787, A61M5/284, A61M2005/3132, A61K9/0019|
|European Classification||A61K9/00M5, A61M5/28M|