JPS58195558A - Head cooling gel for preventing depilation due to side effect of anti-cancer agent - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for manufacturing a head cooling gel, and in particular, a method for manufacturing a head cooling device using polyvinyl alcohol, which has excellent properties not seen in conventional head cooling widths. provide.

The present invention provides cancer chemotherapy (ahθmothθrapy)
Alopecia (alopθcia) as a side effect in
Provides a head cooling gel used to prevent. Suitable for use for the purpose of inhibiting the system of the present invention, special antibiotics (a
Daunorubicin (Daunorubicin) or Adriamycin (Adriamycin) i.e. 1
4-Hydroquinodaunorubicin (doxorubicin) (1
4-hydroxy daunorubicin,
It can be of great utility in preventing and inhibiting severe hair loss as a side effect of drugs such as aoxorubicin. Among these, atriamynon is often noted as an important anticancer agent because it exhibits particularly excellent therapeutic effects against a wide range of cancers, but it is also well known that its toxicity is extremely severe.

This adriamycin (Atriazine, Adriaci)
n) was founded in 3967 at the 7 Almitaria Institute (Italy).
Farmitalia Research Labor
Strθptomycθθ″IJ [J u
mutant strain (muta) of C.
nt') Streptomycespθucθtiu8
It is an anthracycline-type anti-/
Known as one substance (Japan Biochemical Synthesis, Biochemical Data Book L p] 4151979) Tokyo Kagaku Doujin, Airi Ota (edited by Kyosuke Tsuda et al.), "!Current status of pharmaceuticals and their trends 11 (2) p168 (1972) Jijinshokan, A.
Djmarco etal, Cancer Che
mOther, Rep, (1) 53°33 (19
69), F.Arcamone, Chim,
Ind, (Milanol 51.

835 (1969)).

Its antitumor activity
) is widespread, and gastric cancer (ga8tric cancer) is widespread.
er), lung cancer, ovarian tumor, urban cancer (e
mbr-yona'l carcinoma), pediatric tumor (infautile1□ earctnOma),
ile 5 arcosis\breast cancer
ancer ), Wilms tumor (W11m'Stum
or ), lymphatic leukemia
ukemia'), non-phosphoA leukemia (non-1ym
phoid leukemia), Hodgkin's disease (Hodgkin's disease)
gkin's disease'), Sumimaru tumor (o
rchioncus), nasopharyngeal carcinoma (nasopharyngeal carcinoma) (n
asopbaryngealcarcinoma), Ewing's tumor, bladder cancer,
thyroid cancer,
squamous cell carcinoma
inoma), 7g, cancer (cancer of the
pancreas), chorioepithelial carcinoma (chorioep
itelioma), mouse sarcoma 180 (mouse
sarcoma 180), mouse lymphatic leukemia P388 (mouse lymphatic leukemia P388)
kemia), mouse\~~ to leukemia Ll 210 (
For the treatment of mouse leukemia, etc., it is used alone or with other chemotherapeutic agents (chemothθrapeu-
tics) and multi-drug combination methods.
che+notherapy) and used by (A, D
imarco etal,, CancerChem
o℃her, Rep, (1) 53.33 (1969
), Airi Ota (edited by Kyosuke Tsuda et al.)
Jidai Shokan, Mengio Fujimoto (Yoshihisa Nakao ed.) 1.7 All about Leukemia' 1) 412 (198]) Nankodo, Osaka Prefectural Hospital Pharmacists Joint Line, Pharmaceutical Handbook plO] 4 (1981
”) Yakugyo Jihosha), ri') / Mine y (daun
omycin) (1”! usorubicin (daun)
orubicin)) has been reported to be more effective than (
Edited by Osaka Prefectural Hospital Pharmacists Association, 'Drug Handbook' p. 1014
(1981) Yakugyo Jihosha, Airi Ota (edited by Kyosuke Tsuda et al.), 1. Current status and trends of resolute pharmaceuticals” (2) p.

168 (3972) Jijin Shokan).

However, its toxicity is also severe (Dau Qorubicin (Dau Qorubicin (Tsuguchi, Kyosuke et al., eds., Current Status and Trends of Resolute Pharmaceuticals (Part 2), 11, 168 (1972), Chijinshokan), ) indicates the above side effects (edited by the Osaka Prefectural Hospital Pharmacists Association, 'Pharmaceutical Handbook' pIO] 4 (198)) Yakugyo Jihosha, Mengio Fujimoto (
Yoshihisa Nakao (ed.), ``leukemia mousea, vomitus, fever (pyrθxia), mycocardiopathy, renal disorder (n
ephropathy), liver damage (hypohepa
tia), anorexia, decreased red blood cells, bypoleukocytosis, thrombocytopenia, and alopecia, with alopecia being a particularly frequent and notable side effect. Known (Shigeyuki Nagamura et al. (edited by Yoshihisa Nakao), (All About Leukemia) 1), 189 (
1981) Nankodo, edited by the Osaka Prefectural Hospital Pharmacists Association, "Pharmaceutical Handbook" p. 1014 (198)) Yakugyo Jihosha, Airi Ota (edited by Kyosuke Tsuda et al.), 'Current status of new drugs and their trends))
(Bottom) p. 168 (1972) Jijinshokan). In this regard, attempts have been made to reduce side effects by improving administration methods and combining multiple drugs, but normally this alopecia is difficult to avoid, and it is difficult to expect hair regeneration after hair loss (Aiori Ohta (Kyosuke Tsuda) Other editions), 'Current status of new drugs and their trends) 7 (bottom) p.
, 168 (1972) Jijinshokan). For example, adriamycin is administered intravenously every 25 days (j, ntravenou
In patients with s drip), alopecia is observed in more than 90 hairs of patients, and the loss of hair caused by this causes great mental pain to patients, and depending on the patient's level of understanding of modern medicine, it may be difficult to receive medical treatment. It also raises serious problems that can lead to mistrust.

The cause of this hair loss appears to be that antibiotics administered into the body are absorbed into the hair cell tissue, and in order to suppress this absorption rate, the metabolism of the living cells is significantly reduced (2
At around 5°C) 1, gravity has been attempted to cool hair cells. The administered antibiotic reaches the head after a few minutes,
Since it leaves the head within 30 to 40 m1n and is hardly detected in the bloodstream of the head thereafter, a specific method of cooling the head for about 40 minutes after administration has been sought.

In other words, there are methods such as wrapping an ice pack around the head, helmets made of sponge impregnated with a large amount of cold water, and, in history, helmets molded from hollow polyvinyl chloride bags.
Attempts have been made to encapsulate jelly, agar, polyvinyl alcohol/borax gel, etc. However, with the ice pack method, water and ice flow down to the bottom of the bag wrapped around the head due to gravity and become unevenly distributed, making it difficult to uniformly cool the entire head. There are practical difficulties such as poor water retention capacity and large amounts of cold water leaking and dripping.Inside the hollow hat made from a polyvinyl chloride bag.
i' In the method of enclosing a high water content gel as a cooling medium into the cavity, all of the conventionally known high water content hydrogels are fluid (polyvinyl alcohol borax gel, cardiquin methylcellulose gel) or are soft or brittle. Solid (agar,
Jelly, carrageenan, alginate gel), it is difficult to maintain its shape (helmet shape), and it also has poor elasticity, making it difficult to fit tightly onto the head. To prevent the cooling medium from becoming misshapen or unevenly distributed, perforations are made vertically and horizontally over the entire surface of the hollow bag-shaped helmet (many small sections are created).
, an attempt was made to prevent the movement of the internal filling, and an attempt was also proposed to provide a large number of independent vesicles (small inner chambers) within a hollow bag and to enclose a cooling medium in each (Japanese Patent Application Laid-open No. 140107/1983). However, since this helmet itself lacks elasticity, it does not fit tightly to the entire head, creating gaps.
Lacks practical value.

As a measure to prevent hair loss as a side effect of adriamycin, it has been proposed to administer the drug by tightening the scalp with a rubber band, but if we take into consideration the cruel pain that would be caused to the patient by applying external pressure to the head, ,This attempt is not at all desirable either.

The drawback of the above-mentioned head cooling method is that it is not possible to obtain a cold insulation material with appropriate properties, that is, a high water content gel (hydrogel) that has rubber-like elasticity and mechanical strength that can maintain the shape of the helmet. I attribute it to that.

The present inventor searched for a new cold-retaining gel that satisfies the above-mentioned desired properties, and found that a helmet obtained by molding this hydrogel is suitable for the above-mentioned head cooling, thereby completing the present invention. That is, the present invention comprises polyvinyl alcohol with a saponification degree of 95 molar or more, a viscosity average degree of polymerization of 1.500 1', and a water-soluble organic compound, and the concentration of the polyvinyl alcohol is 2.5 to 1. 9 wt%, and a shape that allows an aqueous solution or suspended aqueous solution adjusted to a concentration of the organic compound of 20 to 80 vg% to cover the entire area where the hair, hair and eyebrows, or buttocks (i.e., hair on the left and right sides of the head) exist. After injecting it into the mold that will mold the helmet, it is cooled to a temperature lower than -6℃, solidified, and molded.
To provide a head cooling gel, which is characterized in that it is subjected to vacuum dehydration at a dehydration rate (cooling, weight reduction rate of solidified product) of 5 wt% without melting.

Many attempts have already been made to use water-containing gels (hydrogel) for cold storage, generally as a substitute for ice pillows.
As summarized in (1) to (9) below, all of them have problems in product properties or manufacturing methods, and there are no examples in which they can be used in close contact with the entire head area.

(1) The production of agar gel is well-known as an easy method for producing a hydrogel for cold storage. That is, 0.1 wt% or more, for example 1 to 1 Qw, to hot water or boiling water at 80 to 94°C.
After dissolving agar equivalent to t%, by cooling to room temperature,
A water-containing gel (hydrogel) with a water content of about 90 to 99 wt % can be easily obtained. However, when this gel is cooled in the ice compartment of a refrigerator and then used as a cold-preserving gel, such as an ice pillow or an ice bag substitute, the agar gel has poor elasticity and is extremely brittle. However, the gel disintegrates during use, which is far from providing a comfortable feeling.

In addition, it often freezes and hardens in the ice compartment of a refrigerator, making it inconvenient to use as an ice pillow or ice bag substitute. In this case, the freezing temperature can be lowered by soaking the agar in an antifreeze solution such as ethylene glycol or fluoropylene glycol, or by cooling a heated aqueous solution containing both agar and antifreeze solution. The resulting gel is also brittle and easily disintegrates, making it unsuitable for use in pillows and other cold storage gels.

(2) Similar to agar, monocarrageenan, which contains a D-galactose type structure, a 3°6-Atsuhirogalactose type structure, a partially sulfated polygalactose type structure, etc., can easily form into a hydrogel (water-containing Rate 90
~97wt%), but like agar, it has the disadvantage of being brittle and is also extremely soft. soaking this gel in an aqueous solution of potassium chloride or cal/lam°;
'.

It has been often emphasized for a long time that agar has higher mechanical strength, but even after such post-treatment, the fact remains that it is brittle like agar.

A method of increasing the elasticity of the gel by using carrageena in combination with locust pean gum is also well known, but it is not very effective.

In addition, the fact that it freezes and hardens in the refrigerator icebox and the problems after countermeasures with antifreeze such as ethylene glycol are the same as in the case of agar.

(8) An aqueous solution of a sodium salt of alginic acid containing a D-manuronic acid type structure and an L-guluronic acid type structure can also be extracted from an acidic aqueous solution (pH 2.5 to 5) or Cal/Rum.
By dropping (or immersing) a hydrogel in an aqueous solution containing water-soluble salts such as aluminum, zinc, copper, iron, aluminum, and nickel, a hydrogel with a water content of 97 to 98 wt% can be obtained, but as is well known, this gel also breaks down. It is easy and brittle, and like agar, it freezes and hardens.

[4] Gelatin is also known, but at a gelatin concentration of 2 to 1'5 wt.
Although it is possible to obtain a strong gel by increasing the gel content above 20%, it is a rigid body lacking flexibility, has a low water content, and has the disadvantage of emitting a glue odor.

(5) Konjac containing D-77nose type structure and D-glucose type structure is one of many natural product gels (gelatin, tofu, starch paste, agar, alginic acid, curdlan, carrageenan, farcellan, and cutin). However, it does not easily lose its shape, and has flexibility and some elasticity.
It is a high water content gel with a water content of 97 wt%. but,
When used repeatedly as a cold storage gel, the gel disintegrates rapidly6. In other words, konjac
It is relatively stable as long as it is immersed in an alkaline cold aqueous solution containing aluminum ions with a pH of about 10, but as the lime is repeatedly cooled (freezed) and thawed, precipitation and uneven distribution of lime are promoted. , the gel becomes pasty.

Also, as in the cases (1) to (4) above, it becomes hard when left in a freezer (ice room). Furthermore, since konnyaku easily loses its shape at a pH of about 8 or less, it is necessary to maintain it in a strongly alkaline state at all times, and it is not preferable to repeatedly use such alkaline substances in close contact with the head.

(6) Iron, chromium, aluminum, lead, zinc, and tin salts of CMC (calcexymethylcellulose = sodium cellulose glycolate) have also been proposed, but they are soft pasty gels, and the gel structure often collapses. There is a drawback that it is easy to do so (Special Publication Publication No. 11210/1973). Starch or C
Gels resulting from the reaction of MC with borax (sodium tetraborate decahydrate) are also prominent, but they are also weak.

Furthermore, even if measures are taken to prevent freezing and hardening, and to use antifreeze, the gel is still prone to disintegration.

(7) It has been known for a long time that when boric acid (or boric acid aqueous solution) or borax (or borax aqueous solution) is added to a polyvinyl alcohol aqueous solution, gelation occurs immediately. However, the resulting gel.

It is fluid and soft and can be easily torn into pieces by simply pinching it with your fingertips. In addition, there is a problem of syneresis (separation of water contained) during repeated use (Japanese Patent Publication No. 45-11210).

Refrigerate (freezer) polyvinyl alcohol clouded borax gel
By cooling in an ice chamber, the water in the gel freezes, and in order to prevent the gel from becoming hard, after adding monohydric alcohol, polyhydric alcohol, curcose, or sucrose to the polyvinyl alcohol aqueous solution, A method of gelling with sand has also been proposed, but in this case, the strength of the gel is rather reduced, and there is also the problem that syneresis occurs during repeated use (Japanese Patent Publication No. 1960-1983).

Another method to lower the freezing point of polyvinyl alcohol/borax gel is to immerse the gel in an antifreeze solution such as ethylene glycol or propylene glycol. In addition to further weakening and losing its shape, /.

Antifreeze such as methanol, ethanol, a, etc.
・ It also has the disadvantage that the gel collapses.

(8) Many methods have been proposed for kelizing polyvinyl alcohol using phenols or amine compounds such as phenol, naphthol, and Congo red, or metal compounds such as titanium, chromium, and zirconium.
Both have the same drawbacks as the polyvinyl alcohol borax gel described above.

(9) Crosslinking agents or copolymers of aldehydes, dialdehydes, unsaturated nitriles, diisonanate, trimethylolmelamine, shrimp chlorohydrin, bis-(β-hydroxyethyl) sulfone, polyacrylic acid, dimethylol urea, maleic anhydride, etc. Gelation of polyvinyl alcohol by ingredients is also well known, but in either case, in order to obtain a gel that is difficult to harden in a refrigerator (freezer) or ice chamber, this gel must be immersed in an antifreeze solution such as ethylene glycol for a long time. It is difficult to obtain a gel that is highly flexible.

□ The present inventor utilized po:'nitrivinyl alcohol to produce
Freezer) Store the gel that does not easily freeze in the ice room □′
We studied to develop a method to produce the product in a cost-effective and stable manner.
By cooling, solidifying, and vacuum dehydrating an aqueous solution or suspended aqueous solution containing both polyvinyl alcohol and a water-soluble organic compound, a solid that is highly elastic and flexible, does not lose its shape, and is difficult to freeze. Having obtained the knowledge that a gel can be obtained, the present invention, which has a remarkable effect, has been completed.1.According to the present invention, an aqueous Q or suspended aqueous solution containing both polyvinyl alcohol and a water-soluble organic compound can be gelled. As a result, a gel that is highly elastic and flexible and does not freeze even in a freezer can be obtained. The present invention does not require acids, alkalis, radical sources, radiation, organic solvents, reaction reagents, etc., which are conventionally used in the gelation of synthetic polymers, in the gelation process and its pretreatment process.
No secondary curing treatment or post-treatment to lower the freezing point (temperature) is required. Moreover, the gel obtained by the present invention also has rubber-like elasticity, flexibility, and mechanical strength necessary for a soft (non-freezing hardening) gel for cold storage.

It has been well known for a long time that polyvinyl alcohol aqueous solutions often gel when stored at 0 to 30°C for about 1 day to 1 week, but this gel is brittle like agar and is used, for example, as a cold storage alternative to ice pillows. When this happens, the gel structure collapses, and it also freezes and hardens easily in the freezer. On the other hand, the gel of the present invention has elasticity, flexibility, and strength suitable for use in close contact with the head, and does not freeze or harden even in the freezer, maintaining its original elasticity, flexibility, and strength. do. This means that the present invention provides a gel for cold storage that is completely different from the conventional simple polyvinyl alcohol gel.

The degree of saponification of polyvinyl alcohol used in the present invention is 9
It requires at least 5 mol, preferably at least 97 mol. Even if polyvinyl alcohol with a saponification degree of 80 to 88 molar, especially below 85 molar, is used, only a soft gel is obtained, and the object of the invention is not achieved.

The degree of polymerization of the polyvinyl alcohol used in the present invention is 1.
5001'-J, above is required. Otherwise, only a soft gel will be produced. In the present invention, for example, polyvinyl alcohol with a polymerization degree of about 1,500 to 3,300 can be used, but polyvinyl alcohol with a high polymerization degree (polymerization degree 1,500 to 2,600) is preferably used.

In the present invention, first, an aqueous solution or suspension aqueous solution containing both polyvinyl alcohol and a water-soluble organic compound is prepared. The concentration of polyvinyl alcohol is 2.5 to 10
wt%, preferably 3 to 8 wt%. If this concentration is increased above 10 wt%, the gel tends to be too hard to be used as a head cooling gel, which is not preferable. Further, if this concentration is lower than 2.5 wt%, it is not preferable because it becomes too soft and the gel molded product is likely to lose its shape and collapse.

The present invention is characterized in that, prior to the formation of Geno-J, a water-soluble organic compound as an antifreeze agent (freezing point depressant) is dissolved in the above-mentioned aqueous polyvinyl alcohol solution.1. As this antifreeze agent, For example, ethylene glycol is mentioned. The freezing point of pure ethylene glycol is -16°C, but at a concentration of 38VO1% and 58VO1
% (60wt%) aqueous solution is -23
℃ and -49℃, therefore, the polyvinyl alcohol aqueous solution contains a particularly large amount, for example, the above 58 vol.
% of ethylene glycol is not necessarily required, and the ethylene glycol concentration is 35 to 40 vo
By setting it to about 1%, the freezing point can be lowered to about -20°C, and the object of the present invention can be achieved. This antifreeze effect is not limited to ethylene glycol, but also propylene glycol (40 wt% substitution, -201:), 1
゜3-Propylene glycol (50wt di-substituted, -24
°C), glycerin (49 wt% substitution, -21 °C), 2-
Methyl-2,4-bentanediol (71wt substitution,
-20℃) and other water-soluble polyhydric alcohols 1. Look.

) Straw, Yori, =7. . The temperature drops below -2°11:1□°C, and does not harden in the ice chamber (-10 to -20°C) of a normal household refrigerator (freezer), making it suitable for uses such as ice pillows. Maintains suitable elasticity and flexibility and a feel similar to living tissue.

These polyhydric alcohols, in addition to the above-mentioned action as a freezing point depressant, also contribute to improving the mechanical strength of the cold-retaining gel obtained by the present invention. In other words, compared to gelling a mere polyvinyl alcohol aqueous solution, the coexistence of the polyhydric alcohol significantly increases the gel strength, and therefore polyvinyl alcohol, which normally produces only an extremely soft gel, Even from a low-concentration aqueous solution of alcohol, for example, a 2.5-8 wt % aqueous solution, a cold-retaining gel having mechanical strength suitable for head cooling can be obtained by the coexistence of the polyhydric alcohol. The coexisting concentration of polyhydric alcohol is 20 to BQwt, preferably 3
1. When this coexisting concentration is lower than 20 wt%, it is difficult to lower the freezing/hardening point of the gel to below -10°C.5. In addition, the coexisting concentration is 80w
If it is higher than t%, the freezing point may be lowered unnecessarily, and the freezing/hardening point may even be increased. The freezing/rigidity temperature lowering effect of methyl alcohol (25wt% substitution, freezing point -20℃), ethyl alcohol (30wt% substitution, -20℃), isopropyl alcohol (40wt% substitution, -19℃), ethyl alcohol (40wt% substitution, -21
It is also found in water-soluble monohydric alcohols or their derivatives such as ethoxyisopropyl alcohol (62 wt % substitution, -30 °C), aceto7 (36 wt % substitution, -20 °C), dimethyl sulfokide (37 wt % substitution) , -25°C), methylsulfonic acid (32wt% substitution, 28°C), ethylsulfonic acid (37wt% substitution, -
24°C) Furthermore, dimethylamine (33 wt% substituted,
--20℃), methylamine (20wt% substitution, -20
U), commonly found in water-soluble organic compounds such as formic acid (35 wt% substitution, -20 °C), achieves the purpose of freezing point depression with the advantage of being odorless, with very little volatility, and with a relatively small amount of substitution. Furthermore, in consideration of the mechanical strength of the resulting gel, ethylene glycol, propylene glycol, glycerin, etc. are preferable. Trimethylene glycol (], ]3-7'robilene glycol', 2,4-pentatunool is inferior to the above-mentioned ethylene glycol, propylene glycol, and glycerin in that it emits a faint almond-like odor.In addition, Saccharides (erythritol, arabinose, quinolose, quinolitol, crucose, cul/tol (sorbitol/acid, glucaric acid, galacturonic acid, fructose, curcosamine), di-saccharides (sucrose, cellobiose 4)
lactose), trisaccharides (raffinose), water-soluble polysaccharides (agarose, amylose, sodium alginate,
glycogen, droitin, =1/droitin sulfate,
Dextran, pectic acid, fluoropylene glycose ester, triglyceride gum, pullulan, chondroitin acid (thorium) can be mentioned, but they are already available in Japan.
In 1., it is common for large amounts to be added to foods.

Particularly preferred are 2-prohyrcine glycol (propylene glycol), glycerin, and D-sorbitol.

This is based on the results of animal experiments regarding carcinogenicity, acute toxicity, subacute toxicity, chronic toxicity, etc.
Lnst, U, S, A1 "Carcinogenicity Data Investigation Report", p. 417, p. 147, p. 265, (197
5) Overseas Technical Information Research Institute, Souji Ishibashi, “The Whole Picture of Food Additives”, p. 14 (1-144, p.]2 (1-12
3, p. 140, p. 143 (1971) Nankodo,
Morizo Ishidate, “Food Additives Official Guidebook”, p. B843
, 1:), B251, p, B586 (1979), it is said that there is no problem. For example, propylene glycol is not only added to Chinese noodles, but also used in food layer flavoring, coloring, and preservatives. It is also used as a solvent and is known as a food and pharmaceutical additive that also has a weak bacteriostatic effect (Soji Ishibashi, 1. The complete picture of food additives, p. 140~
144 (197]), Aji Ishibashi, “Food Additives Guidebook” p. 178 (1972') Nankodo, Morizo Ishidate, 1 Food Additives Official Manual, I), B843
(1979'), for floors 11, 1.

bookstore). Grinded phosphorus is known as a wetting agent and humectant for cakes and castella cakes, or as an additive to sake, synthetic sake, Manyumaro, chewing gum, gelatin desserts, meat products, and candy (Ishibashi Soji) , 1. Complete picture of food additives”, p.120-123, p140, p.
-143 (1971), Morizo Ishidate, ``W Food Additives Compendium Commentary'', p.B 251 (1979).

D Sorbitol (hexahydric alcohol) is used in vitamin preparations, amino acid preparations, castella, cakes, gun, yokan, and oral products (11 synthetic alcohol, mayonnaise, /mu, nose = -2,
It is added to soft drinks, miso, soybean oil, vinegar, Narazuke, etc. (Soji Ishibashi, "Food Additives Illustrated Book", I), 35 (1972') Nankodo, Iko Setsushi -,
“Food Additives Official Manual”, p. B589 (1979)
.

These polyhydric alcohols and polyethylene glycols
It is used in cosmetics, toothpaste, lotions, ointments, tablet binders, etc. (Shinzo Ishidate, "Explanation of the Official Standards of Quality Additives", p.B590, p.B846 (1979)
) Floor Bookstore, “Supplementary Commentary on Cosmetic Ingredient Standards”, 1, J. 2
75, p. 68, p. 261, p. 277, p. 278
(1971) Yakuji 11hosha, “Standard Specifications for Cosmetic Ingredients”, p. 53, p. 56, 11, 57, p. 59,
p. 62'). However, 1,4-butanediol and polypropylene glycol are also said to have extremely low toxicity;
, LD5o (white rat) in an animal test by oral administration of 4-buta-7-nol was 2g/. Slf, -f robylene glycol Although not as good as D-sorbitol,
It is generally accepted that the toxicity is extremely low. Polypropylene glycol is also said to have little toxicity, cause no irritation to the skin, and no damage to the cornea.

In addition, the water-soluble organic compounds of the present invention include propylene glycol, glycerin, sorbitol,
Polyethylene glycol, particularly polyzolopylene glycol, 1,4-butanediol; preferred. Of course, sodium alginate, pectic acid, glucose, fructose, sucrose, etc. that are used in food can also be used, but these generally pose a risk of bacterial contamination, so sodium benzoate, potassium sorbate, p-oxygen / It is recommended to add antibacterial agents (preservative additives) such as benzoic acid derivatives, sodium dehydroacetate, and dehydroacetic acid.

The various water-soluble organic compounds mentioned above have a concentration in the aqueous solution of 20 to 8 Qwt%, preferably 35 to 8 Qwt%, as described above.
After adjusting the concentration to 75 wt%, when a dressing material is produced according to the present invention, it is embedded in the dressing material to prevent air drying and hardening of the dressing material, and as mentioned above, the dressing material of the present invention is stored in a freezer (or Provides protection against freezing and hardening when stored in the refrigerator. The amount used is the water retention capacity of each,
Selection is made taking into account hygroscopicity, ability to fall in water, etc. For example, propylene glycol content of 35wt% and 5Qwt.
% aqueous solution is -15℃ and -34℃, respectively.
Both of them are flexible even at 0℃, and even when the coating material of the present invention embedded with them is air-dried at 37℃ for 20 days, the elasticity, flexibility, and suppleness of the coating material are remarkable. There is no difference. Also, the freezing point of an aqueous solution with a glycerin content of 3Qwt% is
Even when the coating material of the present invention embedded at -10°C was cooled at θ°C and 1', no stiffness was observed, and even when it was air-dried at 37°C for 20 days. , again no tendency to rigidity is observed.

Similarly, the freezing and hardening temperatures of an aqueous solution of 32 wt% glucose, 50 wt% lactose, 9 wt% mannitol, or 32 wt% raffinose are -5°C, -7°C, -2°C, -1°C, -, respectively. 1℃,
Again, the same effects as above can be observed.

The above aqueous solution containing both polyvinyl alcohol and a water-soluble organic compound as an air-drying/freezing agent or! !
To prepare a turbid water solution, in addition to adding, dissolving, and suspending hepolyvinyl alcohol in water and the water-soluble organic compound, it is also possible to first dissolve hepolyvinyl alcohol in water and then add it to the water-soluble organic compound. (or its aqueous solution), or add and dissolve polyvinyl alcohol aqueous solution or polyvinyl alcohol powder into the water-soluble organic compound (or its aqueous solution).

In either method, the final concentration of the polyvinyl alcohol-kasumi mill is 2.5 to 10 wt%, and the concentration of the water-soluble organic compound.
Adjust the gourd to 20-80 wt%. In these cases, since polyvinyl alcohol is poorly soluble in solvents other than water, it often takes a state in which transparent microgel particles are dispersed in an aqueous solution of a water-soluble organic compound (transparent M turbid aqueous solution state). There is no problem in carrying out the present invention.

In the present invention, an aqueous solution or suspended aqueous solution containing the above polyvinyl alcohol and a water-soluble organic compound is poured into a desired mold for molding, and is cooled and molded.

In this case, the coolant may be, for example, salt-ice (23 near 7) (-21°C), chloride ice (30 near 0)
(-55℃) or dry ice-methyl alcohol (-72℃), liquid nitrogen (-196℃)
Cool to a temperature lower than -6° C. using a solvent or the like. Furthermore, liquid helium can be cooled down to -269°C, but it is uneconomical, and there is no advantage to the quality of the gel, so in practice it is best to use a Freon refrigerator to cool it to, for example, -20 to -80°C. good. Home refrigerator (freezer) Ice maker (-10~
There is no harm in cooling the sample by storing it at -20°C. This is followed by vacuum dehydration to obtain a solid gel. Note that insufficient cooling is not preferable for the present invention because the mechanical strength of the resulting gel is poor.

Therefore, in the present invention, an aqueous solution or suspended aqueous solution containing polyvinyl alcohol and a water-soluble organic compound is cooled and solidified by reaching a temperature of at least 16°C or lower, preferably 115°C or lower, and then vacuum dehydration. is obtained.

In the present invention, after the above-mentioned cooling treatment, the material is vacuum dehydrated without being melted. As the dehydration rate (weight loss rate of the cooled and solidified gel) increases, the gel's mechanical strength also improves, but if we are to use it as a head cooling cap for patients, it is necessary to significantly increase the dehydration rate and make it stronger. It is not necessary to obtain a gel with a high dehydration rate, and it is preferable from the viewpoint of flexibility and elasticity of the gel to keep the dehydration rate to 60 wt % or more, preferably 5 or more, and 55 wt % or less. The vacuum dehydration referred to herein means dehydration under reduced pressure, and the degree of reduced pressure is not particularly limited, but can be carried out, for example, at 1101 alH or less, preferably 1 wHg or less, and further 0.1 m Hg or less.

This dehydration step cannot be omitted. In other words, if this method is not carried out, the gel of the present invention which is rich in elasticity and has excellent mechanical strength can be obtained.As dehydration progresses, the gel strength increases significantly, and it also has non-stick properties, water resistance, etc. This partial dehydration treatment is indispensable to the present invention, since the various properties of the material are significantly improved. However, in the present invention, there is no need to perform sufficient dehydration (drying) treatment as seen in freeze-drying of injectable liquids or freeze-drying of water-containing foods such as coffee, milk, fruit juice, noodles, etc., and partial dehydration as described in F is not necessary. The purpose of the present invention is fully achieved by the treatment ', and as described above, the gel strength increases significantly as the dehydration progresses, so the amount of dehydration can be selected depending on the desired gel strength.

In any case, this cooling, solidification, and dehydration treatment without melting the molded product is essential to the present invention and is extremely important.1. ”, ', because it has such significance,
If this is omitted, the non-flowable, non-adhesive, highly water-containing hydrogel and excellent mechanical strength described in the present invention will never be obtained.

The gel after vacuum dehydration is a milky white opaque gel, but it is a solid gel that is insoluble in water even at room temperature and cannot be stored in a home refrigerator (
It will not harden even in the ice maker of a freezer.

In the present invention, the shape of the injection container (or mold) for the mixed aqueous solution of polyvinyl alcohol with a water-soluble organic compound or the M turbid aqueous solution is arbitrarily selected, and a helmet molded body (or helmet molding fragment) of a desired shape is produced. It can also be a wet gel (hydrogel).

In this case, the shape of the helmet should not only cover the entire scalp, but also the hair on the left and right sides of the head.
It is desirable that it can also cover the eyebrows, so it can be used as a mere helmet for work or baseball.

Although it is not suitable for use as a helmet for batters in sports, it is possible to easily manufacture the helmet of the present invention by making desired modifications to a mold for molding a helmet used for driving a car, ice hooks, etc.

Although the gel of the present invention contains a large amount of water and water-soluble organic compounds, it has excellent mechanical strength such as konnyaku, agar, alginic acid, carrageena 7, guar com.
Low power Stoene Nawatekam, gels of polysaccharides such as callose, σ rot, ZeIJ-, etc.

Protein gel is far more similar to the muscular structure of humans and animals, and even if you squeeze it tightly, it will temporarily deform, but it will immediately return to its original shape and will not lose its shape.

Even when pressure is applied to the gel of the present invention, almost no leaching of the contained liquid is observed. It's nothing more than that.

The gel of the present invention has no tackiness. That is, even when 10 g of the gel (molded product) of the present invention is immersed in 50-g water and stirred for 10 days, no phenomena such as mutual adhesion or deformation are observed. Even after being soaked in tap water for a year, it did not dissolve, and its elasticity and strength remained unchanged (this is in sharp contrast to, for example, when konnyaku is soaked in tap water for several days, it loses its shape drastically). ).

The texture of the gel of the present invention is similar to that of human or animal meat, squid sashimi, fish, rice cake, chikuwa, hanpen, Japanese yam, or sausage. Therefore, the gel of the present invention can be applied to biological tissue (tiθ5ue), especially flesh-like tissue (d
aytolc tissue), elastic tissue (elas
tic ti8sue). That is, it has the advantages of being highly elastic, having a good texture, not irritating the head, and not sticking to the head.

In the present invention, the helmet-like gel thus obtained can be used as it is (that is, without being packaged or sealed in a bag made of polyvinyl chloride, polyethylene, polypropylene, etc.) as a helmet for keeping the head cool. The feel of the hydrogel of the present invention can be directly transmitted to the head, and since this hydrogel is highly stretchable (elastic), sufficient adhesion is always achieved in accordance with a wide range of head sizes and shapes. In other words, compared to the case where jelly, glue-like synthetic gel, etc. are sealed in a bag made of polyvinyl chloride or rubber, the hydrogel, which has a konnyaku-like (or kuzumochi-like) feel, can be used to directly contact the head. It is clear that the present invention, which reverses this, is much more in line with the humanistic treatment philosophy. In particular, in the present invention, the hydrogel containing glycerin and zolopyrenoglycol (or ethylene glycol) has high water retention properties and is difficult for water to evaporate. Since it is a polyhydric alcohol-embedded gel with excellent water retention properties, it avoids dry stiffness and is always flexible and elastic, with mechanical strength that does not lose its shape and excellent feel (touch).
That is, the original fresh appearance and feel are maintained, and the most desirable effects are exhibited.

In the present invention, a single component of polyvinyl alcohol is used as a gel material (gelled apricot).

)ζ However, the coexistence of other inorganic or organic substances that do not inhibit the gelation of polyvinyl alcohol does not affect the present invention, and the amount of such coexistence can be, for example, below ]/2 weight of polyvinyl alcohol. .

In the present invention, polyvinyl alcohol, which is desired as a cosmetic raw material (“Cosmetic Raw Material Standards Supplementary Notes” p.
279 (1971) Yakuji Nipposha) as well as water-soluble organic compounds that are recognized as foods, food additives, cosmetic raw materials, etc., or are at least harmless to the human body (skin, hair), and contain no chemical reagents or organic solvents. It is characterized by the fact that an excellent hydrogel can be obtained without the use of talc (slaked stone), bentonite, silica, etc., which are well-known as solvents or dispersion media for liniments applied to the skin or hair. Aluminum acid, etc. (Souji Ishibashi, “Overview of Food Additives” 1, p. 138 (197)) Nankodo, Shoji Ishibashi, @Food Additive Guide 1111 Guidebook” 1), ]'74 (1972) Nankodo, “Supplementary Commentary on Cosmetic Ingredient Standards” p. 260 (1971) Yakuji Nipposha, “Japanese Pharmacopoeia 4” (1976) Bookstore)
may be added within a range that does not adversely affect gel strength.

In the present invention, an antibacterial agent can be added to the mixed aqueous solution of polyvinyl alcohol and a water-soluble organic compound from the viewpoint of sanitary observation, that is, disinfection or bacteriostasis of germs in the hair.

It is convenient to add this to a mixed water bath solution of polyvinyl alcohol and polyhydric alcohol, and then, by applying the gelling method of the present invention (cooling, solidification, vacuum dehydration) described above in the same way, After all, a helmet that is highly elastic and feels good to the touch can be obtained. Antibacterial agents that can be used in these cases include, for example, sulfadiazi
faaiazine), silver salurenoiazine (sil
ver 5ulfadiazine), benzalkonium chloride (benzalkonium chl, o
ride'), cetalkonium chloride (cetalk
onium chlorid'e'), methylbe/<\
Zethonium
), neomycin 5ulfa
te), hexachlorophene (hexachlorophene)
hene), eoeine (2/Sy G)
(penicillin G'), -1=77otin (e8p++aloLhin), cephaloridine (
cephalorid 1ne), tetracycline (
tetracycllne), lincomycin (lin
comycin), nystatin (nystat, in
'), kanamycin', peninlinase resistance be5ilver: +actate)
These can be used alone or in combination. Among antibacterial agents, for example, the solubility of sodium sulfadiazine in water is as high as 50 wt %, but only 1 g of sulfadiazine is dissolved in 13,000 - of water. However, in the present invention, it is not necessary to use the antibacterial agent in the form of an aqueous solution, and by adding and mixing the powder or its suspension in the aqueous solution of the polyvinyl alcohol/polyhydric alcohol mixture, the antibacterial agent of the present invention can be used. material)
It can be embedded within.

In the present invention, the amount of antibacterial agent added to the mixed aqueous solution of polyvinyl alcohol and water-soluble organic compound can be 172% by weight or less of the water-soluble organic compound, for example, 0.2 to 4% by weight of acid fladiomyone, Sulfadiazine may be 1 to 25 wt%, Beni/Rin GO may be 62 to 1 wt%, and so on. The antibacterial agent embedded in the gel of the present invention is not washed away in a short period of time, but is embedded and sustainedly released over a long period of time.

For example, 3 wt of sodium sulfacyanone is added to a mixed aqueous solution of polyvinyl alcohol and polyhydric alcohol.
After dissolving the sulfanoazine in the helmet, even if the operation of covering the head of an adult (male) for 40 minutes was repeated 80 times with the helmet obtained by applying the treatment of the present invention.
95% of the sodium content remains, and no bacteria are detected on the inner surface of the herme (the part that comes into contact with the hair and skin).

In the present invention, by cooling, molding, and partially dehydrating an aqueous solution of polyvinyl alcohol/water-soluble organic compound,
It is not clear why a human'□ gel that is completely different from conventionally known polyvinyl alcohol gels, has excellent mechanical strength, is rich in elasticity, and has a pleasant texture, but the cooling process and subsequent partial dehydration treatment are not clear. At times, an extremely large number of hydrogen bonds are formed within and between the molecules of polyvinyl alcohol, which increases the crystallinity of the gel structure and improves mechanical strength and elasticity, especially during partial dehydration. It is assumed that this is due to the fact that

Even if it is a chair, this kind of polyvinyl alcohol cooling
The partially dehydrated gel and its manufacturing method were discovered for the first time by the present inventor.

By subjecting the polyvinyl alcohol gel of the present invention to a known curing treatment for polyvinyl alcohol fibers or polyvinyl alcohol films, the mechanical strength of the gel is further increased slightly.

This known curing (crosslinking) treatment includes, for example, aldehydes, dialdehydes, diisonoanatos, phenols, or metal compounds such as titanium, chromium, and zirconium, as well as borax, acrylonitrile, trimethylolmelamine, shrimp chlorohydrin, Examples include methods using bis-(β-hydroquinethyl)sulfone, polyacrylic acid, dimethylol urea, maleic anhydride, and the like. However, as already mentioned, the gel of the present invention has
1, these secondary hardening treatments are not particularly necessary.

As already mentioned, the hydrogel helmet of the present invention has the following features:
It is non-irritating when it comes in contact with living tissue, does not stick to hair or skin, has a soft texture, sufficient mechanical strength and elasticity, and adheres closely to the head. By cooling this in advance in a refrigerator (freezer) and then wearing it on the head, the exposed skin can be cooled to a desired temperature of 20 to 25° C. when necessary, such as when administering an anticancer drug.

The present invention is effective in inhibiting alopecia caused by side effects of anticancer drugs.1 However, not all anticancer drugs cause hair loss, and the side effects of about 60 representative anticancer drugs currently known include v4 vomiting ( vomituθ), evil also-(na
ueea) to 75 cm each, anureta (anure)
xi,a), leukopenia (1euhopeuia)
) and hemorrhagic tendency (hemorrhag) in 65% and 65%, respectively.
e), diarrhea (diarrh+ea'), thrombocytopenia (thrombocytopeWia), malaise (m
alaisθ) to 45-50%, followed by decreased liver function (bypohepatia) and rash (rash).
), stomatitis fever (pyrex
ia) and hair loss (alopec ia) were observed in over 40 cases each, and head @ (encephalagia)
, nephropathy' (30% each)
, angiodynia, vertigo
gO) Abdomina (+gia), anemia (
anemia), thrombocytopenia (thrombocyto
penia), red blood cell depletion (oligoeryth
rocythemia), phlebitis (phl, ebi,
tis), bone marrow disorder (disorder of bo
ne marrow) thrombus (ihrombosis)
(10-20% each) follow these. Therefore, some people believe that among the well-known anticancer drugs, there are only about 275 cases of hair removal, but in reality, there is a well-known anticancer drug that is regarded as important and is often used: pleomine (
BleOmy-cin, Bleo), Daunorubicin (DaunoNbiCin).

Rubidomycin, 0rde3a, Daun
oblastin, I)aunomycin), atriamycin, adriac
in, Doxoru-bicin'), carboquone, esqui-no
realLquinone,
'? remimon) cyclophosphamide (cycle
Ophosphamide, Endoxan%
Cytoxan, Endoxane), Uramsuti
(Uramuetine.

upioh3, uracjl mustard'),
Mitomycin C (mi tomyc j n CXM
TC), Streptonigrin (TC), Streptonigrin
), vincrietine,
VCR, 0ncovin, Lθmocristine
), vinblastine (VinblasLine, VL
B, Vincaleukoblaθtine, Exal
, Vg 1 b e x V';kIban')
, Demecolcin.

CoJeemidXSubstane F), ActinomycinC (Sanam
ycln), dactinomycin (1) actinom
ycin, cormf3gen XActiwo, m
ycin D'), procarnodine (Procar
bazine7. Nochisura 7, ('+Ibenem
e-shihyZirlo, Natulan), =
Mustine (Nimustine, - Torano, ACNU
), Carmustine 7 (Carmustine, BCN
U), Iho, X7 amide (Ifosfamid, Z
4942), Busulfan, M.
There is always a concern about hair loss with both yleral and mablin.
urea, Hyarea), 5-fluoro-2'
-deoxy/uridine (5-Fluoro-2' -de
oxyuridine, t1UDR), /tarabine (C
ytayabine, Cytoetne, Arabin
oside, kiloside '1cytoean,
Alexander.

1.1 Ara-C, CA), fluorouranyl (
Methotrexate
Lederle, Lederle.

There are also reports of hair loss with well-known anticancer drugs such as AmθLhoptθrin. Therefore, with regard to anticancer drugs that are currently being used preferentially, the frequency of hair loss that is a concern is much higher than the above-mentioned 215, and preventive measures to prevent this side effect are of extremely important significance. Among these anticancer drugs, Vincrietine, Dactinomyci
n.

Daunorubicin, Adriamycin
In such cases, severe hair loss is often noted. Among anticancer drugs that cause hair loss, B]θomycin
Although there are cases where hair regenerates naturally by taking body medications, there are cases where this regeneration cannot necessarily be expected (D
Furthermore, there are cases in which hair regeneration cannot be expected regardless of the administration method or duration of the drug (Adriumy-Cin). Therefore, it goes without saying that it is always preferable to prevent hair loss in advance, not only in these cases, but even in cases where it is thought that hair regeneration is possible.

゛・,′ The Hertz knit of the present invention feels excellent on the scalp when worn, so it can be used without causing pain or discomfort to the patient, and it is extremely easy to put on and take off. However, no matter how comfortable a hydrogel cap is, it cannot be said that wearing a helmet weighing 1 to 2 K9 for a long period of time will not cause some problems to the wearer.

Fortunately, anticancer drugs are generally dissolved in distilled water, physiological saline, or glucose aqueous solution with a concentration of about 1 to 20%, and intravenously administered within a few to 10 minutes.
Ouθ), rarely in the artery (1ntra-artθθ
1a1) R- is shot. Therefore, prior to administration,
The hydrogel helmet of the present invention, which has been cooled to about θ°C, is worn in advance, and after about 10 minutes, the scalp becomes 22-22°C.
After confirming that the temperature has reached 25° C., the injection is performed and the hydrogel helmet is worn for 40 minutes to achieve the purpose of preventing hair loss. In this case, the supine position is still the sitting position.
(Gpoei, tion'), the burden on the patient due to using the Hermenoto of the present invention in close contact with the head is as follows:
is generally considered not to be a problem.

Anticancer drugs are injected into blood vessels, as well as subcutaneously (hypo-
dt+rmin in, 1ection) or intramuscularly (intra, muθc]arinjection
) can also be injected, but in this case, 1 to 2 injections after injection.
The scalp must be cooled for several hours, and if consideration is given to the mental burden of wearing a helmet on the patient during this period, the above-mentioned intravascular injection is preferable. It is desirable to adopt this as long as possible.

As an anticancer drug administration method, in rare cases it takes about 1 to 2 hours to administer the drug.
0 to 500 rnl of the above aqueous solution is injected intravenously (drip).
phleboclyein); however, this prolongation of the administration time forces the patient to wear a helmet continuously during that time, so it is preferable at the discretion of the physician, considering the slight mental burden this may cause. is the above-mentioned intravascular injection of 1 to 20 wt.
When wearing a helmet according to the present invention with a thickness of approximately 20 cm and a diameter of 20 cm (approximately 1.5 to 9) after having been cooled to about θ℃, it is preferable to use the scul, ar 1nJection method. It can be kept cold for several minutes, and the thickness can be increased from 2.5 to 2.5 minutes.
By increasing the length to 3.5m, it can be kept cold for 1.5 hours.

Since it is easy to put on and take off this helmet instantly, it is also possible to use multiple helmets that have been pre-cooled to about 0 degrees Celsius in succession.

For monitoring scalp temperature, it is convenient to use a thermistor (or thermocouple) for measuring skin temperature, which is used, for example, in hypothermia in the surgical field. These thermometer terminals (temperature sensing parts) can be inserted into the hair when wearing a helmet, but in order to monitor the temperature of various parts of the scalp, a large number of thermometer terminals must be inserted into the hair. In order to avoid this complexity, when creating the helmet of the present invention, a desired number of protrusions for molding the thermometry terminal insertion holes are provided on the inner surface of the container for injection molding of an aqueous solution of polyvinyl alcohol/water-soluble organic material. Alternatively, after making a normal-shaped helmet, drill the desired number of small □゛ holes in it, fix the temperature measuring terminal there, and then wear it whenever necessary. .

Hereinafter, embodiments of the present invention will be described.

Example 1 Saponification degree: 99.5 molar ratio, viscosity average polymerization degree: 2,600.
Mix 9.4wt% water iisoog of polyvinyl alcohol with a 4% aqueous solution viscosity (20℃) of 67cP and 500g of ethylene glycol, pour into a 21×25crn bottom polyethylene container, leave to cool at -50℃ for 8 hours, and immediately vacuum dehydrate. was applied to remove 50 g of water (dehydration rate = cooling body weight reduction rate 5 wt%). It has elasticity and flexibility similar to konnyaku, and has mechanical strength superior to konnyaku, exhibiting a compressive strength of 10 to 9/crn2 or more,
fc.

I left this in the ice maker of a home freezer overnight, but it became hard (
It did not freeze (freezing) and could withstand repeated cooling and storage at room temperature, allowing it to be used as a cold insulator.

Comparative Example 1 Example 1 is operated without ethylene glycol. In other words, add 50g of polyvinyl alcohol aqueous solution to -
After cooling (freezing) to 50℃, vacuum dehydration is performed immediately.
□, and 170 g of water was removed (dehydration rate: 34 wt%).

The resulting gel can be frozen and stored in a home freezer ice maker.
It stiffened and turned into a billboard.

Example 2 Saponification degree: 97.5 molar ratio, viscosity average degree of polymerization: 2,200.
630 g of polyvinyl alcohol (water content 7 wt%) with a viscosity of 4% aqueous solution (20°C) 56 cP was mixed with 4,800 g of water.
It was dissolved in 1.4 wt% solution.

4.536 g of this aqueous solution and 2.443 g of polyzolopylene glycol were mixed, 4,536 g of which was poured into a polyethylene container with a bottom surface of 90 x 90 cm and a depth of Icy, and then heated at -50°C. After leaving it for 6 hours, it was immediately subjected to vacuum dehydration to obtain a dehydration rate of 15wt1. The amount of dewatered water reached 680 g and the liquid content reached 91 wt%.

From the sheet-like gel (thickness 5 ttm) thus obtained,
Cut out a 20m x 13m x 5m piece and use it as an in-vivo implantation test sample.

Brush the dorsal skin of a rabbit (weight 2.5 to 9), apply a cloth containing 0.5% chlorohequinone in ethyl alcohol, and disinfect the skin with 70% ethyl alcohol. A .5 crn incision was made, the above test sample (sterilized with alcohol) was implanted, and the skin was sutured.

In this case, care was taken to ensure that the skin incision line was not located on the implanted sample. The findings after 24 hours were skin redness and slight swelling, and when the implanted sample was touched from the skin surface -F, the sample moved through the peeled part of the subcutaneous tissue. After 2 days, the swelling and redness disappeared, and the sutures were removed after 6 days. After 9 days, the sample is already fixed and does not move when touched. For one month thereafter, there was no change in the implanted area, and there were no symptoms throughout the body. 3
After 0 days, the sample including the subcutaneous tissue was extracted, but the sample was wrapped in the encapsulating tissue, and although no adhesion was observed between them, they were in close contact. This encapsulated tissue was treated with 10% formalin (fixed) and embedded in tzeloidin, and then subjected to hematoxylin and eosin double staining and Van Gieson staining. When observed, a small number of pseudoeosinophils and rounded histiocytes were observed. However, cellular infiltration is very mild and inflammatory response is almost absent.

On the other hand, around the catgLI used as a suture,
A strong foreign body tissue reaction was observed even after suture removal. Also, for comparison, 20+u+X 13℃mX 5++ as above
When a sponge of No. Intense cell infiltration and a large number of foreign body cells were observed in the surrounding area of the sponge, indicating that it had turned into a tumor. A similar comparative test was conducted on methyl methacrylate resin, but it took one week for the redness and swelling to disappear, and pseudoeosinophil infiltration was also significant. That is, it was found that the oral gel of the present invention has excellent biocompatibility. 4 Example 3 Saponification degree: 99.5 molar ratio, viscosity average degree of polymerization: 2,600.
4% aqueous solution 9.4 wt % of polyvinyl alcohol with a viscosity (20° C.) of 67 eP, 500 g of the aqueous solution and 500 g of propylene glycol were mixed, 50 wt % of propylene glycol, 4.
7wt: 1□ of aqueous solution was obtained, and this was heated at 120°C x 30 mi dt.
Sterilize with l-pressure steam and leave to cool in a sterile room.

41 g of this water bath solution was poured into a polyethylene beaker (about 9.3 crn in diameter) that had been gas sterilized in advance, and then allowed to stand at -40°C for 6 hours, after which it was vacuumed without melting. Perform dehydration, dehydration rate] Owt%,
The amount of dehydrated water reached 4.1 g and the liquid content reached 94.5 wt%.

This disk-shaped hydrogel has a diameter of 13+wm and a thickness of 1.
Create a small disk-shaped implantation test sample of 5m+. A 3 cm vertical incision was made on the medial side of the knee joint of a domestic rabbit (weight 2.5 to 5+), the medial side of the quadriceps muscle was cut vertically, the patella was dislocated to the outside, the knee joint was flexed, and the anterior part of the knee joint was dislocated. After removing the fat tissue and cutting the chiasm ligament, the joint groove and meniscus other than the posterior joint capsule are removed. Next, the first femoral interphalangeal cartilage was removed, and in place of this cartilage, the above specimen was inserted and fixed on the femoral articular surface. With the knee joint in a 150 degree flexed position, a cast bandage was applied from the upper thigh to the foot. , which was removed after 3 weeks. At this point, there was mild swelling in the joint, but no redness or localized heat sensation; the secondary healing was good, and there was no secretion.
The knee joint has approximately 120 planes of curvature and exhibits protective fractures.
I'll watch. Passive aOJ motion range was 150-900. The tissue specimen was fixed in formalin, embedded in Grafine, and stained with hematokin, eosin, and Mallory staining. Microscopic examination revealed that the femoral articular surface was covered with connective tissue, and the inserted sample showed reactive bone proliferation and bone marrow. No intraluminal inflammatory reactions were observed.

-The same force (when a similar comparative test was carried out on methyl methacrylate resin with a thickness of 1.5 m, it was 31!!
! After 1 hour, findings included swelling in the joint, a localized sensation of heat, and a palpable wave in the upper patella. After the cast bandage is removed, there is a slight amount of passive movement in the knee joint, but almost no automatic joint movement is observed. Furthermore, inflammatory cell infiltration and fibrous scar tissue were observed on the femoral articular surface. In other words, these findings revealed that the hydrogel of the present invention has good biocompatibility.

Example 4 Four pieces of 1.63 cm were cut out from the disc-shaped hydrogel obtained in Example 3 and left at 25°C for one month.
The original weight (400 strokes) remained almost the same at 7L, the volatilization loss of moisture was less than 5wt% (2g), and the original flexibility, elasticity, and texture were maintained.

Comparative Example 2 4.1 g of the polyvinyl alcohol aqueous solution of Example 2 was mixed with 8
The mixture was poured into a rectangular container on the bottom of mX8α and left at room temperature for 2 days, yielding a soft, colorless and transparent wet film. This membrane was immersed in tap water for 6 hours, but not only was it partially dissolved in the water, but the membrane itself was sticky. No rubbery gel as in Example 2 is formed.

That is, simply drying an aqueous polyvinyl alcohol solution does not yield the rubbery high water content gel of the present invention.

Comparative Example 3 Commercially available polyvinyl alcohol having a saponification degree of 78.5 molar and a clay average degree of polymerization of 1,800.4% aqueous solution viscosity (20° C.) of 36 cP was used in the polyvinyl alcohol solution of Example 2, and the same operation was carried out. . Freezing/molding/dehydration 7.4
g (moisture content 55 wt%) was obtained, but after thawing it was 5℃
The mixture also softened, and in addition to a small amount of gel layer, a concentrated aqueous solution of polyvinyl alcohol was observed to separate into layers. That is, even if polyvinyl alcohol with a low degree of saponification is used, the water-resistant gel of the present invention cannot be obtained.

Comparative Example 4 In place of the polyvinyl alcohol of Example 1, a commercially available polyvinyl alcohol having a saponification degree of 99.2 molar and a clay average degree of polymerization of 500.4% and an aqueous solution viscosity (20°C) of 56 cP was used. 20g of 18wt% aqueous solution was frozen and
Although it was molded and dehydrated, only 13 g of a brittle gel (water content 72 wt%) resembling agar was obtained, and it was found that it had almost no elasticity. That is, even if polyvinyl alcohol with a low degree of polymerization is used, the rubber-like elastic gel of the present invention with excellent mechanical strength cannot be obtained.

Comparative Example 5 The concentration of a polyvinyl alcohol aqueous solution with a polymerization degree of 506'□ as in Comparative Example 4 was increased to 30 wt i'', and 120 g of the water solution was frozen and molded at 3°C for 1 h.
''1, vacuum dehydration was performed for 6 hours. After thawing 106 g of the frozen, molded, and dehydrated product (water content 66 wt%), it was immersed in water for 8 hours, and as a result, it absorbed up to 120 g (water content 70 wt%) and significantly It softened, and some of it lost its shape (dissolved in water).

Comparative Example 6 In Example 3, polyvinyl alcohol (saponification degree 9
9.4 molar ratio, clay average polymerization degree 2,600) 6wt
After cooling (freezing and molding) 34 g of % aqueous solution, it was left at room temperature for 1 hour. A sticky soft gel (34 g s, dehydration rate 0%, water content 94 wt) was obtained, but it did not show elasticity and its tensile strength was It was already broken at only 100 g/J. Also, when the gel log was immersed in 30 g/J of water, about 20 g/J
Over time, it lost its shape and the water layer became cloudy and mostly sticky.

In this way, even if a polyvinyl alcohol aqueous solution is frozen and molded and thawed, only a sticky gel with low strength and poor water resistance is obtained. The strong water-resistant red tar referred to in the present invention will not be produced unless it is subjected to the following steps. "1 Comparative Example 7 Polyvinyl alcohol powder of Example 1 (water content gwt%
) and 0.5 g each of carboquine methylcellulose
Add to 90g of water, boil for 15 minutes to dissolve, let cool to room temperature, mix vigorously, and then
This was left to cool (frozen) at -50°C and immediately vacuum-dried to obtain 1 g of a dried product. This was a styrofoam-like white sponge that was even more fragile, and easily turned into a sticky liquid in water.

That is, even if an operation according to the present invention is performed on an aqueous solution of about 0.5 wt % polyvinyl alcohol, it is unlikely that a mere aqueous lyophilized product will be obtained.

Comparative Example 8 A polyvinyl alcohol/borax gel, which is often used in practical use as a cold storage gel, is synthesized in a conventional manner 3.
Namely, H. Thele et al.

KullOid z, 173.63 (1960),
H-Deuel, H, Neukon.

MakromolekuLare Chemiθ,,
3.13 (194(J), 1.G.

FarI+c+old, ndust, rie Akt,,
Fr, 743942 (1933) etc. in the needle groove,
10 g of polyvinyl allure powder (water content 7 wt%) with a saponification degree of 97.5 molar and a clay average polymerization degree of 2,000 was dissolved in 90 g of water to prepare 100 g of a 9.3 wt% solution. (sodium tetraborate) anhydride aqueous solution (2.5 wt%, 0.12M Na2B4O7
, pH 9,65) 100-.

The pH after injection reached 9.45, and a large amount of gel was immediately observed to separate. The surface of the gel mass obtained by separating about 60 mm of the aqueous phase was lightly washed with a small amount of water (50 m) to obtain 142 g of a brittle gel in the shape of .xi. This gel is
It was white and translucent, and because it immediately lost its shape when pinched with the fingertips and had some fluidity, it could be filled into containers of any shape (sealed containers).

Place this soft gel in the ice chamber (-15℃) of a household freezer for 4 hours.
When the gel was left to stand for a while, the entire gel froze, turning into a rigid solid that was as good as ice.

On the other hand, add 10g of this soft gel to 10g of ethylene glycol.
When soaked in water, it lost its shape after an hour and became soft over time. Similarly, when it was soaked in 10 g of glycerin, it lost its shape after 0.5 hours and turned into a viscous paste. When the gel was similarly immersed in methyl alcohol 10-, the liquid phase became viscous and the gel was broken into many fragile pieces. It has already been shown in 1. that the formation of polyvinyl alcohol/borax gel is inhibited by the coexistence of glycerin and the like. N1ckerson
(J, Appl.

Po+ym, Sci, 15.111 (1971)
) also points out.

Nafu... Moisture of this soft gel (100℃X) for 6 hours.

Evaporation content) was 92 wt%.

In this way, polyvinyl alcohol × borax gel (Special Publication No. 4a-21858, Special Publication No. 4a-21858, Special Publication No. 4
5-11210, Special Publication No. 45-36572, Special Publication No. 1973
-19601), the aforementioned I, G, F, (19
33), C, S, Marvel (J, Am, Ch
em, Soc, 60.1045 (193s), S
,5a1to(Kolloia Z,, 144+ 4
1111□ (1955)), H,0chiai (Polynia
r (G, B, R,) + 21, (5): and.

Despite many studies such as 485 (1980) '), it always has a paste-like, putty-like, jelly-like, or silty-like appearance, is brittle, soft, and has poor elasticity.
It was confirmed that it has the disadvantage of being invaded by alcohols that are useful as freezing point depressants.

Comparative Example 9 Saponification degree: 97.5 mol%, viscosity average degree of polymerization: 2,200.
630 g of polyvinyl alcohol (water content 7 wt%) with a viscosity of 4% aqueous solution (20°C) 56 cP was mixed with 4.800 g of water.
]], to obtain a dWt solution.

4,536 g of this aqueous solution and 2.443 g of glycerin
Mixed with polyvinyl alcohol concentration 7.4 wtl
, an aqueous solution with a glycerin concentration of 35 wt% was obtained, and 12
Sterilize with 0CX 30ml pressurized steam and leave to cool in a sterile room. This water-soluble IIl! 170g was placed in a square stainless steel container (
7 x 7 x 3.5 crn) at -50°C.
After cooling overnight, it was allowed to stand at room temperature to melt. After cooling it again in the freezer and repeating the operation of leaving it indoors during the summer, water separation (separation 1,...) occurred during indoor discharge.

It was repeatedly observed that: 1, the weight after 12 repeated operations decreased to 54 wt% (110 g') of the original weight.
Towards the east, the dimensions of the gel itself also shrunk to 6x6x3t-rn.

In addition, the gel that has contracted in this way has extremely poor elasticity and does not easily expand or contract.

Regarding mechanical strength, it is too weak before syneresis;
It was determined that it would not withstand molding and would lose its shape.

The low-temperature gel of a mixed aqueous solution of polyvinyl alcohol and glycerin has been well known for a long time, but it has already been reported that it is only as strong as gelatin or agar (Dario Hirai, 8).
74. (3) 235.63.259 (1953
)).

On the contrary, it is clear that the gelling method of the present invention, which performs vacuum dehydration on a molded product without cooling, solidifying, or melting the molded product, is particularly superior.

Regarding the cooled, solidified, and molded product of Example 1, the above-mentioned difficulties (syneresis and shrinkage) were confirmed unless vacuum dehydration was applied to the product.

Low-temperature gelation of an aqueous solution of polyhinyl alcohol and methyl alcohol is also well known (Kinzo Ishikawa et al., Tamayo, 55, 736).
(1952), Gisaku Takahashi, 13.502 (1956))
.

However, when methyl alcohol is used instead of ethylene glycol in Example 1, and it is cooled and solidified, and then melted without vacuum dehydration, only a soft gel is obtained, and syneresis after being left at room temperature for a period of time.・The aforementioned difficulties such as shrinkage were also addressed.

Example 5 Saponification degree: 99.5 mol%, viscosity average degree of polymerization: 2,600.
Mix 10wt% aqueous solution IK9 and 500g of propylene glycol with polyvinyl alcohol having a viscosity of 67 cP (viscosity of 4-chi aqueous solution at 20°C), and put this into a helmet molding mold with a long outer diameter of 23 cm, a short outer diameter of 20 cm, and a thickness of about 2 cm. After pouring and cooling at −43° C. for 8 hours, vacuum dehydration was immediately performed (without melting) to remove 200 g of water, and then the mixture was left at room temperature.

The top and right side of the helmet-shaped hydrogel thus obtained,
Drill 2.1 ml of blood through 4 holes on the left side and the back of the head, insert the thermometer terminals of the thermistor for measuring skin temperature into these holes according to the thickness of the gel, and then insert the temperature at each insertion point (
It was glued and fixed by applying adhesive Aron Alpha to the outer surface of the helmet.

This helmet was left in a freezer icemaker (-18°C) overnight, but it did not freeze or harden, and retained its original flexibility and elasticity. Leave this at room temperature and
When the temperature indicated by the thermistor reached 0°C, the thermistor was placed on the head of an adult (long-haired boy) and was placed in a supine position. After 8 minutes, the thermistor's reading reached 20 to 22°C, and then 3
It was maintained at 20-25°C for 5 min. The composition of this helmet is 7.5wt% polyvinyl alcohol.
, propylene glycol was 38 wt%, and water was 54 wt%.

Patent uL Nippon Oil Co., Ltd. procedural amendment (voluntary) June 11, 1980 Patent jF Director Shima ") Haruki Tono 1 Incident indication" 1982 Z1 Patent Application No. 77502 2 Name of the invention Prevention of hair loss due to side effects of anticancer drugs 3. Person who makes the amendment Head cooling care" Relationship with 1'l Patent applicant 4 Agent 6 Number of inventions to be increased by amendment .

3 7 p1415 p, 1415
3 9 p168 p, 1683
15 1nfautile
1nfantile3 17 1nf
autile 1nfantile4
1 orchi
orchi-4145353 416p168 p, 1684 17
p412 p, 4124 18
plo14 p, 10145 9
p1014 p, 10145
18 mentioned, especially mentioned, especially 6
10 Intravenous administration Administration 6 11
drip 1njection16
l titanium titanium 1613 obtain or obtain 18 10 invention
Invention 24 16 (1979),
(1979') 25 11 79).
79)).

27 3 Covering material Gel (covering material) 6 11
especially desirable 36 20 not to disturb 38 4 5ulfete
5ulfate38 14 (Covering material) (Covering material, helmet) 40 11 Titanium Titanium 41 15 (diarrh
ea) (diarrhea), 41 18 (st
omatitis) (atomatitis), 42
1 (angiodynia) (an
diodynia), 42 2 (verti
go) (vertlg, o), 42 5
marrow), marrow),
43 7 (Procarbazine,
(Procarbazine), 43 7 Noteslan, Noteslan 43 8, thyz
ine thyzin44 14 Talk about your hopes and entrust your hopes 45 7 artesi
al arteria146 15 thickness approx. 20crn thickness approx. 2.0 46 3 burden 48 20
54 14 Clay Viscosity 55
5 Clay viscosity 56 5 Clay viscosity 57 20 Clay viscosity □ Supplementary city council (voluntary) 1971 policy July 19 [] 1] 'Toshio Wakasugi, Commissioner of the Patent Office 1! No of INN? Showa (l157'l Patent Application No. 77502)
Q2 Name of the invention Preventing hair loss due to side effects of hair removal I
For L 3 Person making the amendment Head s cold storage game'' 4T Relationship with PI Patent applicant fl: l'lI I in i';S (octagonal) (444) Nippon Oil Co., Ltd. 5 Assignment - Date of order □

Claims (1)

[Claims] Contains polyvinyl alcohol with a saponification degree of 95 molar or more and a viscosity average polymerization degree of 1,500 or more and a water-soluble organic compound, and the concentration of the polyvinyl alcohol is 25 to 10 wt.
%, and an aqueous solution or suspended aqueous solution adjusted to a concentration of 20 to 80 wt% of the organic compound is injected into a mold for forming a helmet having a shape that can cover the hair or the entire area where the hair and eyebrows exist, and then - A method for producing a head cooling gel, characterized in that the solidified and molded body obtained by cooling to a temperature lower than 6° C. is subjected to vacuum dehydration at a dehydration rate of Swt-E without melting the solidified and molded body.