JPH0271745A - Water-contained gel composition - Google Patents

Abstract

PURPOSE:To enhance the water retentivity, a shape holding ability and a flexibility by blending alpha-tricalcium phosphate into an ointment containing a water-soluble polymer having a carboxyl group and water. CONSTITUTION:0.01 to 15wt.% of alpha-type tricalcium phosphate (alpha-TCP) is blended in an ointment containing a water-soluble polymer having a carboxyl group and water. The water-soluble polymer such as, a carboxyl group of soda polyacrylate or the like reacts upon alpha-TCP in the ointment so as to cross-link the water-soluble polymer which therefore forms a stable structure having an excellent water-retentivity and shape holding ability. In this case, the cross- linkage is suitable while the manipulative control is easy with no discoloration, but there are no ununiform blocks due to partial hardening and further the ointment is never hardened with the time lapse. Further, it is possible to have features such as no sagging, sticking and the like even though it has a uniform flexibility.

Description

Detailed Description of the Invention (a) Industrial Application Field The present invention is a hydrogel with improved water retention, shape retention, and flexibility by incorporating α-tricalcium phosphate. The present invention relates to a composition.

([+) Prior Art Conventionally, water-containing pads have been used to prevent bedsores and bedsores, and have been applied to affected areas to relieve local acute inflammation accompanied by fever such as bruises and sprains, or to relieve muscle stiffness. Water-containing patches are commercially available. Such a hydrogel composition is generally made into a gel by adding a wetting agent such as glycerin or sorbitol, water and a gelling agent such as gelatin or polyvinyl alcohol to an inorganic substance such as kaolin, bentonite, talc, or ZnO, or , these hydrogels are blended with medicinal ingredients such as menthol, camphor, salochol, methyl salicylate, etc., and then spread on a support.

(c) Problems to be Solved by the Invention However, with such hydrogel compositions, the paste softens during hot summer months, causing blurring, becoming sticky, and causing stains on the support side. It was sometimes difficult to remove the release paper, and the paste remained on the skin after application, making the application site unclean. Furthermore, there were problems such as a decrease in water retention, rapid evaporation of water, and a decrease in adhesive strength due to hardening of the base in winter.

On the other hand, in order to solve these problems, various studies have been made, such as crosslinking of polyacrylate with a compound having an epoxy group, crosslinking of PVA with a compound having an aldehyde group, crosslinking of PEG with an isocyanate, or , crosslinking of polyacrylates with polyvalent metal salts including aluminum, etc. However, epoxy crosslinking is difficult to control, aldehyde crosslinking has problems such as discoloration, insufficient adhesive strength, and hardening of the paste, and isocyanate crosslinking has safety problems.
Metal crosslinking has problems such as forming non-uniform blocks, weak crosslinking effects, and hardening of the paste in proportion to the amount added.

As mentioned above, although various methods have been tried, a satisfactory and ideal hydrogel composition has not yet appeared.

(=) Means for solving the problem In view of the above situation, the inventors developed a water-containing gel composition that has unprecedented water-retention and shape-retention properties and is highly flexible. In order to achieve this goal, we focused on metal crosslinking, which is considered to be the easiest to operate among the various crosslinking methods mentioned above, and as a result of intensive research, we have developed a method that can be applied to a plaster containing a water-soluble polymer having a carboxyl group and water. α-type tricalcium phosphate (C
It has been discovered that the objective can be effectively achieved by blending as(POa)z) (hereinafter abbreviated as α-TCP). That is, the present invention relates to a hydrogel composition characterized in that 0.01 to 15% by weight of α-TCP is blended as an essential component in the plaster component.

Specifically, the water-soluble polymer in the paste, such as the carboxyl group of sodium polyacrylate, reacts with α-TCP, thereby crosslinking the water-soluble polymer, resulting in excellent water retention and shape retention. It forms a stable structure, and compared to other crosslinking methods, ■ Crosslinking is moderate and operation control is easy.

■ No discoloration.

■ There is no possibility of partial curing resulting in uneven blocks.

■ The plaster does not become hard over time.

■ While maintaining a certain level of flexibility, there is no sagging or stickiness.

The present invention has been completed based on the discovery that the present invention has the following characteristics.

Hereinafter, the present invention will be specifically explained in more detail.

α-TCP used in the present invention is a tasteless and odorless white amorphous powder. Depending on the production method, TCP produces α-form and β-form. The α-form is obtained by melting and quenching at a high temperature of 1100°C or higher, and the β-form is obtained by melting at a temperature of 1100°C or lower. However, β-TCP has a very weak chemical activity (the one used in the present invention is α-TCP, which has high reactivity).
-TCP is preferred.

Conventionally, α-TCP has been known as a precursor of hydroxyapatite, which has recently attracted increasing attention because of its similarity to bone and tooth bud components, and α-TCP itself can be hardened by reaction with hardening liquid. As a result, in the medical field, applications have been developed for lining materials, luting agents, root canal filling materials, bone cement, bone defect repair materials, etc. However, there is no example of obtaining a hydrogel composition using α-TCP, and furthermore, there is no example of applying this composition to the hydrogel composition described below (and there are no known documents suggesting this, i.e. , highly active α-TCP
exhibits hydration hydraulic properties, so if a hydrogel composition containing water is obtained using it, it will form a block of highly cured material similar to cement, so the composition cannot be used as a hydrogel adhesive composition. It was the state of the art of those skilled in the art that it would be difficult to utilize it as a. However, despite having the fixed technical concept as described above, the inventors of the present application have conducted various studies regarding α-TCP, and as a result, they have found that α-TCP has excellent water retention, shape retention, and flexibility. They discovered that a gel composition could be created. Furthermore, α-TCP
There is no example of using this as a crosslinking agent in a hydrogel composition, and this is a new finding that was first discovered by the inventors of the present application.

The blending amount of α-TCP is 0.01 to 15% by weight, preferably 0.05 to 10% by weight based on the entire hydrogel composition.
is desirable. If it is less than 0.01%, the crosslinking force will be weak, the curing of the paste will be insufficient, and wobbling will occur. On the other hand, if it exceeds 15%, the degree of crosslinking will be strong, resulting in hardening during production, and furthermore, the product will lack flexibility.

Next, examples of water-soluble polymers with carboxyl groups include polyacrylic acid, polymethacrylic acid, sodium polyacrylate, carboxyvinyl polymer, ethylene,
Examples include maleic anhydride copolymer, isobutylene/maleic anhydride copolymer, methyl vinyl ether/maleic anhydride copolymer, and rings therebetween. The amount of these water-soluble polymers is not particularly limited, but is usually 1 to 20% of the total hydrogel composition. Also, the water content is 1
It can be adjusted between 0 and 90%.

The hydrogel composition obtained by the present invention can be used in various products for which gel compositions have conventionally been used, either as is or by adding other components as necessary. In addition, specifically, it can be used for applications such as pads for preventing bed slippage, gels for treating bedsores, wound protection materials, water-containing patch compositions such as medical poultices, cold insulation materials, and gel fragrance materials.

As mentioned above, the water-containing gel composition of the present invention can be sufficiently used for various purposes even with the above composition, but other components may be arbitrarily blended as necessary. Other optional components that may be added will be explained below. The medical bar mentioned above
When using the water-containing gel composition of the present application as a drug, the drug contained therein is not particularly limited as long as it is a transdermal drug (for example, as a skin irritant and analgesic anti-inflammatory agent, salicylic acid, methyl salicylate, salicylic acid Glycol, β-
Menthol, camphor, pepper oil, thymol, nicotinic acid benzyl ester, capsicum extract, kabsaicin, nonylic acid vanillylamide, pentazocine, butyl flufenamate, piroxicam, indomethacin, ketoprofen, pranoprofen, fueprazone, loxoprofen, diclozenaf sodium, diflunisal,
Zomepirac, ibuprofen piconol, pendazac, and suprofen, and their ester derivatives.

Central nervous system agents include fluphenazine, thioridazine, diazepam, chlorpromazine, nitrazepam, etc.

Antihypertensive diuretics such as hydrothiazide, bendronate lunathiazide, and reserpine.

Clonidine, etc. as an antihypertensive agent.

Coronary vasodilators include nitroglycerin, nitroglycol, isosorbite cinitrate, papaverine hydrochloride,
dipyridamole, nifedipine, etc.

Procaterol, isoproterenol, theophylline, etc. as agents for treating bronchial asthma.

Indenolol, propranolol, pindolol, carteolol, timolol, etc. as β-blockers.

Antihistamines and antiallergic agents include diphenhydramine hydrochloride, chlorpheniramine, diphenyl imitasol, chlorpheniramine maleate, glycyrrhetinic acid, tranilast, ketotifen, etc.

Adrenal corticosteroids include hydrocortisone acetate, hydrocortisone, prednisolone, doriamcinolone acetonide, dexamethacin phosphate, methylprednisolone, glycolidune acetate, methylprednisolone acetate, fluocinolone acetonide, dexamethacin acetate, dexamethacin, fluorometholone, phosphoric acid betamethacin sodium, betamethacin, betamethacin valerate,
Beclomethasone propionate, fludroxycortide,
Hydrocortisone butyrate, betamethacin dipropionate,
Fluocinonide, clobetasol propionate, diflucortolone valerate, haldinonide, amcinonide, prednisolone valerate, etc.

Examples of local anesthetics include lidocaine, ethyl aminobenzoate, procaine hydrochloride, dibucaine, and procaine.

These medicinal ingredients may be used alone or in combination of two or more.

Next, there are no particular restrictions on the polymer base as a base component (
Examples of softening agents include silicone-based, styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene prosol copolymer, acrylic, vinyl ether, natural rubber, urethane, and polyisobutylene. The oil or higher fatty acid used is selected from liquid paraffin, olive oil, camellia oil, almond oil, basic oil, peanut oil, oleic acid, and the like.

Next, the water-soluble polymer is selected from gelatin, polyvinyl alcohol, methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, gum arabic, sodium alginate, polyvinylpyrrolidone, polyvinyl methyl ether, pectin, polyethylene oxide, and the like.

The humectant is selected from glycerin, sorbitol, maltitol, ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, 1,3-butylene glycol, and the like.

Next, examples of inorganic fillers include kaolin, bentonite, talc, titanium dioxide, zinc oxide, calcium carbonate, and hydrous aluminum silicate.

Next, as pH adjusting agents, lactic acid, citric acid, tartaric acid, ascorbic acid, succinic acid, oxalic acid, phosphoric acid, malic acid,
Acetic acid etc. are used.

Next, as preservatives, thymol, methylparaben, ethylparaben, butylparaben, etc.

Next, rosin resins, terpene resins, petroleum resins, phenol resins, xylene resins, etc. are used as tackifiers.

Next, as a water-absorbing resin, specifically, Sanyo Chemical's "
"Sunwet", "Aqua Keep" by Steel Manufacturing Chemicals, "Sumikagel" by Jusumi Chemical, and "Arasorb" by Haruyo Chemical.
etc.

Next, as a stabilizer, polysorbate 80, sucrose fatty acid ester, benzophenone compound (for example, 2-hydroxy-4-methoxyhensiphenone), urea, etc. are used.

Next, dibutylhydroxytoluene (B
IT) etc.

Next, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, etc. are used as surfactants.

Next, as transdermal absorption enhancers, isopropyl myristate, isopropyl palmitate, diisopropyl adipate, benzyl alcohol, crotamiton, diethyl sebacate, pyrrolidones, "Eisin", etc.

Furthermore, conventionally known fragrances and the like can be appropriately blended depending on the purpose.

Examples of the support include films or sheets of polyethylene, polypropylene, polybutadiene, ethylene vinyl acetate copolymer, polyvinyl chloride, polyester, nylon, polyurethane, or porous bodies and foams thereof, as well as paper, cloth, nonwoven fabric, etc. To be elected.

Next, as the manufacturing method of the present invention, for example, α-TCP and a water-soluble polymer having a carboxyl group are sufficiently mixed and dispersed in a polyhydric alcohol, and this is gradually added to water, and other additives are added as necessary. is added to prepare a water-containing composition. Furthermore, after uniformly blending the drug according to the purpose, it is spread on a nonwoven fabric.
The product is then covered with release paper and cut into the desired size.

(N) Effects of the Invention The α-TCP-containing hydrogel composition obtained by the present invention has water retention, shape retention, and flexibility that cannot be obtained by conventional crosslinking methods, as described in Examples and Test Examples below. It has excellent properties as a medical device.

Furthermore, even if drugs are mixed, it will not be sticky or sticky (
Moreover, it has excellent adhesion to the skin, and also good drug release from the plaster, making it an excellent transdermal absorption preparation.

Moreover, it is highly safe as it causes very little skin irritation.
It has high utility value as a medical base.

Next, the present invention will be explained in more detail by Examples and Test Examples, and its effects will be shown.

It has been recognized for its usefulness as an ideal cold insulating material that does not lose its elasticity or get wet to the touch even when exposed to heat.

Example 1 α-TCP 5.0% Sodium polyacrylate 10.0% Gelatin
3.0% glycerin
20.0% water
62.0% 100.0% α-TCP and sodium polyacrylate are gradually added to glycerin and sufficiently stirred to disperse and mix until it becomes a paste. Next, the above paste is added to water in which gelatin is dissolved while heating, and kneaded until uniform. This was cooled and used as an ice pack.

Since Honjima shows good water retention and shape retention, and has excellent flexibility, it does not lose its shape, sag, or become sticky, and can be applied to the skin for a long time.Example 2 α-TCP 2 .5% Sodium polyacrylate 7.5% Polyvinyl alcohol 2.5% Lactic acid
2.0% water
85.5% 100.0% A cold insulating material was prepared according to the manufacturing method of Example 1.

The main island was found to be useful as in Example 1.

Example 3 α-TCP Sodium polyacrylate polyvinyl alcohol glycerin 6.0% 12.5% 3.5% 16.0% thymol lactic acid water 0.1% 4.0% 57.9% 100.0% A cold insulating material was prepared according to the manufacturing method of Example 1.

The main island was found to be useful as in Example 1.

Example 4 α-T CP 3.7% methyl vinyl ether/maleic anhydride copolymer 7
．． 1% Gelatin 5.0% Glycerin 52.4% 31.8% 100.0% A wound protection material was prepared according to the manufacturing method of Example 1.

The main island was found to be useful as in Example 1.

Example 5 α-T CP 5.0% Sodium polyacrylate 10.0% Gelatin
3.0% glycerin
20.0% methyl salicylate
1.0%〃-Camphor 0.8
%l-menthol 0.5% water
59.7%io
o, o% Methyl salicylate, a-camphor, and 1-menthol were added as medicinal ingredients to the hydrogel composition prepared in Example 1, and after uniformly dissolving them, they were spread on a nonwoven fabric, and then spread on a polyethylene film. The covered product was cut into a desired size and used as a poultice.

Compared to the comparative Pa-Nobu formulation that does not contain α-TCP, Motojima has higher plaster cohesiveness, water retention, and shape retention, and exhibits good skin adhesion, and has excellent transdermal absorption. It was recognized that it had excellent properties.

Example 6 α-TCP 2.5% Sodium polyacrylate 7.5% Polyvinyl alcohol 2.5% Lactic acid
2.0% Thymol o
, i% Ketoprofen 0.3% Peppermint oil 1.0% Water
84.1%100.
0% A medicinal ingredient was added to the hydrogel composition prepared in Example 2, and a Pa-Nobu preparation was prepared in the same manner as in Example 5.

Honjima showed the same excellent characteristics as Example 5.

Example 7 α-TCP Sopolyvinylalcoglycerin polyacrylate 6.0% -Dar 12.5% -R 3.5% 16.0% Thymol 0.1% Lactic acid
4.0% Ketotifen fumarate 1.0% Water
56.9% 100.0% A medicinal ingredient was added to the hydrogel composition prepared in Example 3, and a poultice was prepared in the same manner as in Example 5.

Honjima showed the same excellent characteristics as Example 5.

Example 8 α-T CP 3.7% Methyl and Nylethe; Cy/Maleic Anhydride Copolymer
7.1% gelatin 5.0% glycerin 51.7% thymol
0.2% propranolol
0.5% water
31.8% 100.0% A medicinal ingredient was added to the hydrogel composition prepared in Example 4, and a poultice was prepared in the same manner as in Example 5.

Honjima showed the same excellent characteristics as Example 5.

It was adjusted.

Comparative example 1 potassium alum Sodium polyacrylate gelatin glycerin water According to the manufacturing method of Example 1, It was adjusted.

Comparative example 2 aluminum hydroxide Sodium polyacrylate polyvinyl alcohol lactic acid According to the manufacturing method of Example 1, 5.0% 10.0% 3.0% 20.0% 62.0% 100.0% Hydrogel composition 2.5% 7.5% 2.5% 2.0% 85.5% ioo, o% Hydrogel composition Comparative example 3 Sodium polyacrylate polyvinyl alcohol glycerin thymol lactic acid water According to the manufacturing method of Example 1, It was adjusted.

Comparative example 4 aluminum hydroxide Sodium polyacrylate polyvinyl alcohol lactic acid thymol Ketoprofen 12.5% 3.5% 16.0% 0.1% 4.0% 63.9% 100.0% Hydrogel composition 2.5% 7.5% 2.5% 2.0% 0.1% 0.3% mustard oil water 1.0% 84.1% 100.0% A poultice was prepared according to the manufacturing method of Example 5.

Ratio-axis side 5 Methyl vinyl ether/maleic anhydride copolymer
't, t% gelatin 5.
0% glycerin 51.7% thymol 0.2% propranolol 0.5% water
31.8% too, o% A poultice was prepared according to the manufacturing method of Example 5.

It was stored for one month.

One month later, each sample was taken out and evaluated for stickiness, protrusion of the plaster, discoloration, adhesion to the liner, bleeding, and plaster remaining on the skin. The results are shown in Table 1.

The evaluation criteria are as follows.

-: Not at all ±: Slightly present +: A small amount +: A large amount Table 1 Test Example 1 Samples from Examples 1 to 8 and Comparative Examples 1 to 5 were placed in a thermostatic chamber at 40°C and 75% humidity. Place each in a bag, Procedural amendment (voluntary) Name of the invention indicated in the case 1986 Patent application No. 8 H Shisui ν 7 Ibufu hydrogel composition Date of the amendment order by the person making the amendment Voluntary 5, In the specification to be amended , "3. Detailed Description of the Invention" Column No. 67 + 11 In the specification, "fixed" in the 6th line immediately below the 6th line of the "3. Detailed Description of the Invention" column is deleted.

(2) In the same book, in the second line from the bottom of page 7, the phrase "as is, or" is corrected to "as is, or J."

(3) In the same book, from the 2nd line to the 12th line from just above the 11th line, ``There are no particular restrictions...Next, as a water-soluble polymer'' is deleted.

In the same book, from the eighth line from the bottom of page 12 to the fifth line from the top of page 13, ``Next, as a tackifier...Next, dibutylhydroxytoluene (BHT) etc. as an antioxidant.

” to be deleted.

1'+51 In the same book, page 12, line 8 from the bottom, ""
Eishin” etc. '' should be corrected to read ``Dodecyl azacyclopentane derivatives such as Eisin ■.''

Procedural amendment (spontaneous) 1゜Indication of the case Patent Application No. 8967 of 1989 2゜Name of the invention Hydrogel composition 3゜Person making the amendment 4゜Date of amendment order Voluntary 5゜Subject of amendment 1989 4 ``Contents of amendment'' of the procedural amendment submitted on May 12th
Column 6゜Contents of amendment The written amendment submitted on April 12, 1989 will be corrected as follows.

ll

Claims (2)

[Claims] (1) A hydrogel composition characterized in that α-tricalcium phosphate is blended into a paste containing a water-soluble polymer having a carboxyl group and water. (2) The hydrogel composition according to claim 1, wherein the amount of α-tricalcium phosphate is 0.01 to 15% by weight of the entire plaster.