JPS63159317A - Allantoin-containing aqueous preparation - Google Patents

Abstract

PURPOSE:To obtain the titled aqueous preparation stably maintaining allantoin for a long period, showing high treating effects, by blending an allantoin- containing aqueous preparation with an organic acid, inorganic acid, amino acid or an alkali metallic salt thereof as a stabilizer. CONSTITUTION:An allantoin-containing aqueous preparation is blended with 0.01-20wt% organic acid (e.g. citric acid, tartaric acid or succinic acid), inorganic acid (e.g. phosphoric acid, polyphosphoric acid or hydrochloric acid), amino acid (e.g. glutamic acid, aspartic acid or glycine) or alkaline metallic salt thereof as a stabilizer. In the preparation, allantoin partially exists in a dissolved state and the preparation exhibits higher treating effects on ulcer, wound, decubitus, congelation and burn than an ointment or powder using an existing oily base.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention relates to an allantoin-containing aqueous preparation in which allantoin is stably blended, and particularly for treating ulcers, wounds, bed sores, etc. in which allantoin is stably retained over a period of time. This invention relates to an aqueous preparation containing allantoin for the treatment of frostbite and burns.

[Prior Art] External preparations containing allantoin or its aluminum derivative have been known as therapeutic agents for skin and mucous membrane lesions, ulcers, etc. caused by burns and injuries. Conventional ointments containing allantoin or its aluminum derivatives are made of petrolatum, lanolin, paraffin, wax, higher alcohol, etc., and when applied to the affected area, the exudate from the affected area spreads to 9 and 11 tissues. ilf may be absorbed, resulting in a delay in treatment. In addition, when a powder containing allantoin or its aluminum;-ul-derivative is used, it has poor adhesion to the affected area because it is a powder;
It has the disadvantage of falling off the affected area and scattering onto the patient's clothes.

- A common drawback of the powders, ointments, and powders is that allantoin or its aluminum derivative exists in a crystalline state, resulting in poor release properties, making them unfavorable for treatment. These drawbacks can be overcome by including water in the formulation. That is, by containing water,
When applied to the ta area, the affected area, 1. - It does not form an oily film on the surface, has excellent adhesion, and can melt allantoin or its derivatives to form a preparation with good release properties. However, allantoin or its aluminum
-+4 conductors are very unstable in the presence of water, and for this reason, these materials containing water have not hitherto been available.

[Problems to be solved by the invention] The present invention provides an aqueous preparation containing allantoin,
The object of the present invention is to provide an aqueous preparation that stably retains allantoin for a long period of time.

[Structure of the Invention] [Means for Solving the Problems] The present invention provides an aqueous formulation containing an effective amount of allantoin, an organic acid, an inorganic acid, an amino acid, an alkali metal salt thereof, or two or more thereof. This is a stable allantoin-containing preparation characterized by containing and blending the allantoin combination in an aqueous base. At that time, as the allantoin described in 07r, aluminum di-LD IJ xialant inate or aluminum di-LD IJ xialant inate can be used. Further, the organic acid may be citric acid, tartaric acid, citric acid, :1 citric acid, asu-17 lebic acid, and the like.

11;12 Inorganic acids are phosphoric acid, metaphosphoric acid, and polyphosphoric acid.

And II can be made into phosphoric acid, acetic acid, hydrochloric acid, etc., and the alkali metals are sodium, potassium, and calcium, and there are 4 towns! ,
The amino acids include glutamic acid, aspadigic acid,
Greenn, Ashin, Barin, 0ishin, In [1
Isine, serine, threonine, etc. can be used.

In the aqueous preparation containing effective allantoin 11 of the present invention, the aluminum derivative of allantoin includes:
Examples include aluminum chlorhito[+xialantoinate], aluminum dihyde 11 xialantoinate, and the like. There are three types of stabilizers used according to the invention in the formulation of allantoin, an aluminum derivative of allantoin: organic acids, IIA-free acids, and amino acids.

In the present invention, organic acids refer to organic acids such as citric acid, tartaric acid, lactic acid, citric acid, :1 uccinic acid, and as:I lupic acid. , metaphosphoric acid, polyphosphoric acid.

In the present invention, amino acids include glutamic acid, aspartic acid, glycine, allantoin, leucine, iso-Uisine, I! The amino acids used in the present invention, such as amino acids such as phosphorus and 1-thionine, include both acidic and neutral amino acids.

One such stabilizer is blended into the formulation of the present invention, and its blending amount varies depending on the base material contained in the formulation, but it is preferably in the range of about 0.01 to 20%. .

The formulation according to the invention contains water. That is, it is applicable to all aqueous preparations, and cream shavers (W2O or 6
7y), not limited to u-silicone agents, but also liniment M, poultices, pasta agents, gel-like soft and
It can be applied to a wide range of sweat agents, etc. The base component is not particularly limited, and other components may be added as necessary.
Active ingredients and base ingredients can also be added and used.

Therefore, the formulation of the present invention may contain preservatives and emulsifiers, as necessary, to the extent that they do not impair the effects of the present invention.

Antioxidants, sequestrants, thickeners, etc. can be added.

When allantoin is combined with the above-mentioned specific amino acids or organic or inorganic acids in a formulation, the stability over time (El) of allantoin is lower than when the above-mentioned specific amino acids or organic or inorganic acids are not included. The present invention has been made based on the discovery that the present invention is significantly improved.

In the preparation according to the present invention, since water and allantoin or its aluminum derivative coexist, and allantoin or its aluminum derivative exists in a partially dissolved state, compared to ointment M or powder using a conventional oil base, It is highly effective in treating ulcers, wounds, bedsores, frostbite, and burns.

Next, the aqueous preparation containing allantoin of the present invention will be explained using common examples and compared with comparative examples, but the explanation will be limited to the following explanation. isn't it.

[Examples 1 to 3 and Comparative Examples 1 to 3] A, Yatanol 6.0g So←Rin 10.0g Glychrin e/Ir
'I fatty acid Nisdel 2. OgTween60
4. Og myristic acid isobu U pill 1
0.0g Bilparaben 0.1g
B, 17-bylene glycol 10.0g Aluminum chloride 1 Xialantoinate 6.0g Methylparaben 0.1゜Purified water
Take component B and each additive shown in the table below, add purified water to make a total of 67.9 g, and add 7
Component A was heated and dissolved at 5°C, separately heated and dissolved at 75°C, added to the dissolved B component and additives, emulsified and mixed, cooled to 25°C, and compared as shown in Table 1. Examples 1-3
and Examples 1 to 3 were prepared.

The preparations prepared as in , - were stored at 50"C for one month and then taken out. The residual allantoin was extracted with IN hydrochloric acid and determined by the high-speed liquid evaporation method using the 1.J Madograph method. The results are as follows. Shown in the table below.

Table 1 Additive Addition M Allantoin Comparative Example 1 - -- 60.2% times
Sodium dihydroxide 0.5% 41.0% times 3
Triphenolamine 0.5%
57, 1% Example 1 Metaphosphoric acid 0.5%
98.9% times 2 Quest 7 Ml 3%
99, 9% Comparative Examples 1 and 2.3 are examples in which no additive was used or additives other than the stabilizer used in the present invention were blended.0 Example 1 in which the stabilizer used in the present invention was blended - 3 shows that compared to Comparative Examples 1 to 3, the aging of alumina l, nido [1
1) It is clear that the stability has deteriorated by 1.

[Example 4-1] [++-Syn/i1] Allantoin 5.0g Zinc oxide
10.0g Glychlin
3.0g Microcrystalline Cell U-s 2.5g
Carboxymethylcell U-zu 2.5g lactic acid
4.0g purified water
73.0゜ [Add a small amount of microcrystalline cellulose and carboquine methyl cellulose to purified water in the proportions shown below.
Add '1', thoroughly moisten and dissolve, then use α
Next, allantoin, zinc oxide, and glycerin were mixed uniformly as described in 1-1 and added to the microcrystalline cellulose, lurose, and carboxymethyl cellulose melt prepared in Step 11. Add lactic acid and mix evenly.

An El-sin agent was prepared.

[Example 4-2] Allantoin 5.0g bent lead oxide
10.0g Geritrin
3.0g microcrystalline cell "I-s"
2.5g carboxymethylcellulose polyphosphoric acid 4.0 glutamic acid 2.0g purified water
71.0gWith the above ratio, microcrystalline cell [
1. Add carboxymethyl torurose little by little to purified water and moisten thoroughly. Transfer the dissolved material to a river. Next, add allantoin, zinc oxide, and glycerin to the mixture of microcrystalline cellulose and carboxymethyl cellulose prepared previously. Add polyphosphoric acid and glutamic acid to the mixture to make the total balance, and make U-
I made a Shikun medicine.

[Example 4-3] Allantoin 5.0g Oxide IIIi
Lead 10.0g glycerin
3.0g microcrystalline cell days
2.5g carboxymethyl cell [1-s 2,
5g Quen #4. Og Asparagine Ilv [2.0g Purified water 71.0g at a ratio of 2 parts. Add microcrystalline cells [j-s, carboxymethyl cells 1)-s little by little to purified water, and stir well for 11 in. Prepare something that has not been dissolved. Next, separately asyntoin, zinc oxide,
Glycerin was uniformly mixed with ht as described in -1-, and then the microcrystalline cell U-s and carboxymethyl cell U-s prepared previously were mixed.
- Add to the mixture. Further, citric acid and aspartic acid were added and mixed uniformly to prepare an n-john agent.

[Example 4-4] Allantoin 5.0g zinc oxide
10.0g glycerin
3.0g microcrystalline cellulose 2
．． 5g carboxymethiJ recellulose 2.5g birophosphoric acid 4. Og sake stone cup
2.0g purified water
71.0g Add a small amount of microcrystalline cellulose and carboxymethyl cellulose to purified water in the above proportions, sufficiently moisten and dissolve. Next, allantoin and zinc IvI chloride lyserine were uniformly mixed and bound into the microcrystalline cell "1" prepared previously.
-s, carboxymethyl cell [λ.
, further add tartaric acid and PIIJ phosphoric acid and mix uniformly, r
An i-silicone drug was prepared.

[Example 5] [Paste agent] Allantoin 6.0g Benzalkonium chloride 0.1g Purified lanolin 1
2g Chink oil 75g Meclic acid 2g Purified water 4ml Metaphosphoric acid, allantoin, benzal chloride in purified water; 1
Add Nitrium and disperse. Add purified lanolin and mix well. Chink oil was added and mixed well to make it homogeneous, and a pasta paste was prepared.

[Example 6] [Liniment agent] Aluminum chlorhito 11 xialantoinate 6.0 g Zinc white starch 10.0 g Tragacanth powder
5.0g glycerin
3.0g Glutamic acid 3.0g
Purified water 73.0g Put purified water in a mixer, add 9 pieces of tragacanth powder while stirring and dissolve, then add zinc oxide starch, aluminum lamb [1 L xialantoinate, glutamic acid, and glycerin] and mix evenly. A liniment preparation was prepared by mixing thoroughly until the mixture was mixed.

[Example 7-1] [Soft/H] Aluminum di-L-do-U xycintoinate 3. Og Carboxybi J-Rubolimer-0.3g Triethanolamine 0.05g Gluglutamine l'i 1.5g Propylene Glycol 10g Purified Water
Add carboxyvinyl polymer, aluminum dihydroxyallantoinate, and glutamic acid to 85.15gJ11m water, mix well, and dissolve.
After adding propylene glycol and mixing, 0.05 g of triethanolamine was added and gelatinized to prepare an ointment.

[Example 7-21 Aluminum,--N11-dih-do-H-xyacycintoinate 3. Og Carpoxyvinylborine - 0.3g Triethanolamine 0.05g Glutamic acid 1.5g Pr-11pyrene glycol 10.0g Metaphosphoric acid
1.5g purified water
Carboxyvinyl polymer, aluminum di-L-do[I]-xialantoinate, glutamic acid, and metaphosphoric acid were added to 85.65 g of purified water, mixed well, and dissolved. Further, propylene glycol was added and mixed, and then triethanolamine was added. An ointment was prepared by adding 0.05 g of the ointment and gelling it.

[Example 7-3] Aluminilla 12 dihyde 11 xyacycintoinate 3.0 g carboxyvinyl polymer 0.3 g triethanolamine 0.05 g glutamic acid
1.5g
10. Og Ass: 1 Lupine 19 1
．． 5g purified water 85.65g purified water, add carboxyvinyl polymer, aluminum di-L-droxyallantoinate, glutamic acid, and aspartic acid, mix well, dissolve, add propylene glycol, mix, and add triethanolamine 0 .0
An ointment was prepared by adding 5 g of the mixture and gelling it.

[Example 7-41 Aluminum, '-U11 dihd [I xyacintoy] 3.0 g Carboxybin, -ruboline - 0.3 g Tricho'6-tanolamine 0.05 g Glutamic acid
1.5g [I pyrene glycol]
10.0g aspartic acid 1.
5g purified water 85.65g Add carboxyvinyl polymer, aluminum dihydroxyacintoinate, glutamic acid, and aspartic acid to purified water, mix well, dissolve, and then add P-I'! Pyrene glycol: After adding 1-l and mixing, triethanolamine 0
．． An ointment was prepared by adding 0.05 g of the ointment and gelling it.

[Example 8] [Poultice] Carboxyvinyl polymer 2g purified water
75g Sodium polyacrylate 3.5g Methylpaciben
O, 1g notyl buffen
0.1g pilpaciben
0.04 g 5% aluminum chloride 12 liters, liquid
3.5g delta glycol nosictone
2゜0870% sorbitol liquid 1
0.0 g 5% sodium chloride 2
．． 0g Aluminum Oxide 8. Og Aspacigin # 4.0g - With the following formulation, firstly, carboxyvinyl polymer was added to purified water, firstly, aluminum chlorhito-U xialantoinate, aspartic acid, and polyacrylic acid were added, dissolved and kneaded, and then delta Mix glyco1nolactone and 70% sorbitol solution. Then 3.5% 5% aluminum chloride solution
g. 11 liquids of 5% sodium hydroxide were added to form a gelatinous material.The prepared gelatinous material was applied to a heat-retaining 'Noilno, 1-' to prepare a Panno-made potato.

[Comparative Examples 4 to 8] Using the same manufacturing method and composition as in Examples 4 to 8, 1 contained the stable side according to the present invention, and allantoin or its aluminum 1
1 derivatives for external use.

Comparative Examples 4 to 8 were given.

The stability of allantoin was tested for the formulations of Examples 4-8 and Comparative Examples 4-8 when stored at room temperature. The results are shown in the table below.The residual allantoin content after 1', 1l number of hts was determined by high-speed liquid dilution. It was analyzed using Matogushi Soi. The remarkable stabilizing effect of the allantoin-containing aqueous formulation according to the invention is clear from this table.

In addition, in the Examples and Comparative Examples in Section E, allantoin
The operating conditions of the high-speed liquid rig [1 Mado Grasoy] used earlier are:
Using NH, color, and 9 analysis temperatures at room temperature, using an ultraviolet absorption photometer (measurement wavelength: 230 nm), moving phase: NH.
, H, PO, Niahitonitrile Parable 1:3.

Table 2 Stability of Allantoin [Effects of the Invention] The allantoin-stabilized aqueous preparation of the present invention has, firstly, remarkable stability of allantoin.

A remarkable gamma lantoin residual rate is provided, and secondly,
Thirdly, in the preparation according to the present invention, alan:-yne co-fuses with water in a partially dissolved state, so compared to MM of other manufacturing methods. As a result, technical effects such as the ability to provide high healing effects were obtained.

Claims (6)

[Claims] (1) In an aqueous preparation containing an effective amount of allantoin, by containing an organic acid, an inorganic acid, an amino acid, an alkali metal salt thereof, or a combination of two or more thereof as a stabilizer for allantoin, the allantoin An allantoin-containing aqueous preparation, characterized in that it is stably blended with an aqueous base. (2) The allantoin-containing aqueous preparation according to claim 1, wherein the allantoin is aluminum dihydroxyallantoinate or aluminum chlorohydroxyallantoinate. (3) The allantoin-containing aqueous preparation according to claim 1, wherein the organic acid is citric acid, tartaric acid, oxalic acid, succinic acid, or ascorbic acid. (4) The inorganic acid is phosphoric acid, metaphosphoric acid, polyphosphoric acid,
Claim 1 No. 1 which is pyrophosphoric acid, acetic acid or hydrochloric acid
Allantoin-containing aqueous preparations described in Section 1. (5) The allantoin-containing aqueous preparation according to claim 1, wherein the alkali metal is sodium, potassium, or calcium. (6) The amino acids are glutamic acid, aspartic acid,
The allantoin-containing aqueous preparation according to claim 1, which is glycine, alanine, valine, leucine, isoleucine, serine, or threonine.