JP2000095676A - Soft capsule including vitamin b12 - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a soft capsule including a stably formulated vitamin B12 by packing a composition comprising granules containing the vitamin B12, an oily medicine and a specific surfactant. SOLUTION: This soft capsule is obtained by charging (B) a soft capsule with (A) a composition comprising (i) vitamin B12-containing granules having preferably 75-250 μm, more preferably 106-180 μm particle diameter, (ii) an oily medicine (e.g. a corn oil) preferably containing a wax, and (iii) a surfactant (e.g. a fatty acid ester of glycerol) having 1-9 HLB, and preferably having 500-50,000 Pa.S viscosity. The component (i) is produced by adding an additive (e.g. a gelatin) to the vitamin B12 by a conventional method. The ratio of the formulated vitamin B12 to the additive is preferably (1:5)-(1:200). A fluidized bed granulation, an extrusion granulation, a crushing granulation, a microcapsulation or the like is cited as the granulating method.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to relates to a soft capsule which was stably blended vitamin B _12.

[0002]

BACKGROUND OF THE INVENTION Vitamin B ₁₂ is a glutamic acid methyl aspartate nucleic acid precursors, since it directly involved in nucleic acid synthesis, are important factors in protein synthesis.
Therefore, vitamin B ₁₂ may grow hematopoietic involved in such myelin sheath formation of neural tissue, are known as one of the vitamins essential to the human body.

Conventionally, vitamin B ₁₂ is used in prescription drugs or counter drugs and insurance agents, light, pH, relative moisture, are known to be unstable. It is known that vitamin B ₁₂ is relatively stable to temperature and oxygen in a dry state, but becomes extremely poor when other vitamins are added. For example, the addition of vitamin B _1, B ₂ and B ₆ Vitamin B ₁₂ Vitamin B ₁₂ has been reported to decompose (home remedy Research, No.1
1, 33 (1992) 33-40). Therefore, various measures for the stabilization of vitamin B ₁₂ in the formulation have been made. For example, in the case of an injection, the pH is adjusted to 4.5 to 5.5 in the Japanese Pharmacopoeia, and in the case of tablets, sugar coating is used to prevent instability due to light and moisture.

[0004]

[SUMMARY OF THE INVENTION On the other hand, soft capsule has the advantage of taking is easy, because the vitamin B ₁₂ by moisture agent mesothelial is decomposed, the conventional vitamin B ₁₂ containing soft capsule It was not commercially available. Accordingly, an object of the present invention is to provide a stable vitamin B ₁₂ containing soft capsule.

[0005]

In view of such circumstances SUMMARY OF THE INVENTION The present inventors as a result of intense research, filled with vitamin B ₁₂ and granulate, which in the soft capsules with a surfactant and oil having a specific HLB You can get a stable vitamin B ₁₂
The present inventors have found that a soft capsule can be obtained and completed the present invention.

Namely, the present invention is to provide vitamin B ₁₂ containing granulated product, a soft capsule obtained by filling a composition comprising the surfactant oil and HLB1～9.

[0007]

Of DETAILED DESCRIPTION OF THE INVENTION The composition to be filled in the soft capsule of the present invention, vitamin B ₁₂ are formulated as granules. When blended vitamin B ₁₂ as a granulated product, dramatically stability is improved compared with the case of compounding it. Granulation may be performed by a conventional method with the addition of additives. Examples of the granulation method include fluidized bed granulation, extrusion granulation, pulverization granulation, microencapsulation, and the like. Particle size is 75
２５０250 μm, particularly preferably
It is preferably 180 μm. Additives used for granulation include lactose, starch, gum arabic, dextrin, crystalline cellulose, bulking agents such as gelatin, lubricants,
Pharmaceutical additives such as disintegrants, pH adjusters, solubilizers, thickeners, adsorbents, etc. are mentioned, and dextrin, gelatin and gum arabic are more preferred. Compounding ratio of the additive and the vitamin B ₁₂ (weight ratio) 1: 5 to 1: 200, especially 1:10
１ ： 1: 100 is preferred.

[0008] The oil agent used in the present invention is not particularly limited as long as it is an oil generally used for soft capsules. Oils include corn oil, soybean oil, rapeseed oil,
Sesame oil, coconut oil, safflower oil, cottonseed oil, olive oil,
Examples include vegetable oils such as salad oil, animal fats such as lard, beef tallow, fish oil, whale oil, and shark liver oil, and these may be used alone or in combination of two or more. The amount of oil, relative to vitamin B ₁₂ containing granulated product, 10 to 100 times by weight or so, it is preferable to use particularly 10 to 50 times by weight.

However, when the granules are added to the oil,
Granules may settle and become non-uniform. For this reason, a stirring operation is required, but it is often difficult to maintain uniformity only by stirring. Therefore, the viscosity of the oil agent is adjusted to uniformly disperse the granules. For this reason, it is preferable to add a wax having a high melting point such as beeswax, wood wax, spermaceti, hydrogenated vegetable wax, etc., which are compatible with the above oil agent. Here, the viscosity of a suitable filling composition is 500
５０50,000 mPa · s, especially 2,000 to 20,000
mPa · s is preferred.

In the present invention, by blending the capsule filling the surfactant HLB1～9, both resistance to destabilization of vitamin B ₁₂ by improving the hygroscopicity of capsule disintegration is satisfied . That is, when a surfactant is not added, the disintegration of the capsule is not sufficient. On the other hand, when a surfactant exceeding HLB 9 is blended, the disintegration of the capsule is fast, but vitamin B
₁₂ may become unstable.

The surfactants of HLB 1 to 9 include glycerin fatty acid ester, sorbitan fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene castor oil, sucrose fatty acid ester, polyoxyethylene block polymer, polyoxyethylene alkyl ether, polyoxyethylene It is preferable to select and use ones having HLB of 1 to 9, especially 2 to 9 among ethylene sorbitan fatty acid esters and the like. Among these surfactants, glycerin fatty acid ester, sorbitan fatty acid ester, sucrose fatty acid ester and the like are particularly preferable. The amount of the HLB 1 to 9 surfactant to be added is preferably 1 to 50% by weight, particularly preferably 8 to 20% by weight, based on the base oil.

Further, the filling of the soft capsule of the present invention may be
In addition to the above ingredients, preservatives, coloring agents, flavors, flavoring
Agent, solubilizer, antioxidant, pH regulator, thickener, stabilization
Agents, dispersants and the like can be added. Note that HLB1
0 or more surfactants do not impair the effects of the present invention
Can be blended. But water, polyethylene
Recalls, propylene glycols, lower alcohols
With vitamins, vitamin B ₁₂May destabilize
Therefore, it is preferable not to substantially mix them.

The soft capsule of the present invention can be obtained by filling the soft capsule obtained by the above method into a soft capsule by a conventional method such as a rotary die method or a flat plate method.

[0014]

Soft capsule of the present invention according to the present invention can be stably blended unstable vitamin B _12. In particular, it is effective when combined with other vitamin preparations.

[0015]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

[0016] about 60 ° C. while the production of gelatin 10g of Example 1 (1) vitamin B ₁₂ containing granulated product stirred in water 90g
To dissolve the gelatin. Next, the gelatin solution is cooled to about 40 ° C., 0.1 g of vitamin B ₁₂ is added, and the mixture is stirred and uniformly dissolved. This solution is sprayed at a drying temperature of 80 to 85 ° C. using a laboratory spray dryer manufactured by Yamato Scientific to obtain a powder. 80-120mesh powder obtained by spray drying
To obtain a uniform B ₁₂ containing granules sieved through a sieve. (2) surfactant production following Table 1 capsule filling and white beeswax and corn oil and mixing ratio of vitamin B ₁₂ containing granulated product obtained in (1) 1
15 mixed at 0: 10: 100: 10 (weight ratio)
g of thiamine nitrate 0.75 g and pyridoxine hydrochloride 0.6
g (viscosity of 10,000 mPa · s) was charged to about half of the No. 5 bottle. The bottle was left open in a thermo-hygrostat (Nagano Kagaku LH-20) set at 40 ° C. and 75% RH, and changes in appearance after 3 months were observed. Table 1 shows the results.

[0017]

[Table 1]

[0018] than the results in Table 1, vitamin B ₁₂ containing granulated product, a capsule filling containing a combination of surfactant oil and HLB2~9 was stable after long-term storage.

Example 2 In Example 1, 0.1 g of a filler containing glycerin fatty acid ester, sorbitan fatty acid ester or sucrose fatty acid ester as a surfactant was filled in a No. 2 oval capsule to obtain a soft capsule. The obtained soft capsules were stable even when stored for a long time, had no content decrease after storage for 3 months, and had good disintegration properties.

Continued on the front page (72) Inventor Emimoto Emi, 168 Hisazawa, Fuji-shi, Shizuoka Tokai Capsule F-term (reference) 4C076 AA56 BB01 CC24 FF63 4C086 AA01 AA02 DA39 MA03 MA05 MA37 MA52 NA03 ZC24

Claims (3)

[Claims] 1. A vitamin B ₁₂ containing granulated product, oil and HL
Soft capsules filled with a composition containing the surfactants of B1 to B9. 2. The soft capsule according to claim 1, wherein the oil agent contains a wax. 3. The composition to be filled has a viscosity of 500 to 50.
The soft capsule according to claim 1, which has a viscosity of 000 mPa · s.