JPH06509060A - Therapeutic and cosmetic compositions for treating the skin - 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] Therapeutic and Cosmetic Compositions for Treating the Skin Background of the Invention The present invention relates to gastropods for use in therapeutic and cosmetic compositions. od) (e.g. snail).

The composition is applied to the skin or various mucous membranes.

Products obtained from snails are used in various medical products and methods. It is. β- obtained from the sac fluid of the snail He1ix pomatis Glucuronidase is a method for detecting morphine and its analogues, as well as steroids. used in enzyme studies involving the metabolism of (see U.S. Pat. No. 4,473,640, issued in 1999). liver disease Vaccines, especially those for administration to cattle, are Lymnaea natalen manufactured from sis (P, K, rice issued to Bitakaramire) (See National Patent No. 4,314,992). produced by snails Treating yeast cells with a polysaccharide hydrolase that degrades the walls (T , U.S. Patent No. 3.889.006 issued to Nagasawa et al. (see ). From Keyhole limpet (marine gastropod mollusk) Serum proteins such as hemocyanin can be used to treat peptides administered to primate animals. Modified and used to control biological activities caused by chorionic gonadotropin (V.

See U.S. Pat. No. 4,855,285 issued to C. ).

U.S. Pat. No. 3,885,012 (issued to Tschesche et al.) Homogenized edible snails of the genus Ielix and family Helicidae, e.g. , He1ix pomatia) from protease inhibitors (iso-inhibitors). Discloses that it is manufactured.

The iso-inhibitor of the 012 patent is produced from dead edible snails of certain genera and families. discloses chemically treated products obtained from manufacturing iso-inhibitor The homogenized mixture used for edible snail blood, muscle, kidney, Contains lungs and excreta.゛ Dead animals used in O12 compositions using a frozen shelled snail, the starting product obtained is Contains the products from the animal's last biological reaction. In addition, the product It may also contain toxic substances from the muscles of other animals and pathogenic viruses from the excreta.

Iso-inhibitors are: (a) Homogenize, i.e., crush, frozen snails with shells); (b) Obtain The resulting homogenate is separated into a precipitate and a supernatant, and the separation is generally about 12.00 (performed by centrifugation for 60 min at Orpm (24,0OOG)): (C) Mix the supernatant with ammonium sulfate to a saturation concentration of 63% to obtain protea. -precipitate the inhibitor: and (d) optionally fractionating the substance by gel fractionation and selecting the most active fraction; or optionally fractionate the material on a cation exchange resin to obtain different isoisomers. - Obtain a large number of fractions containing the inhibitor Manufactured by

°　Medical applications for O12 compositions are negative and varied. Applicable to acute pancreas inflammation, obstructive thrombus, plugging, stopping bleeding in the maxillary sinus. Treatment of thrombotic or bleeding conditions including , esophageal varices in cirrhosis, and uterine cancer. Injectable aqueous solutions containing iso-inhibitors for use in. Three suggested One of the prophylactic uses of blood is to prevent radiation damage in the irradiation of malignant growths (i.e., carcinomas). It is a decrease.

Radiation dermatitis (i.e., exposure to radiant energy sources such as X-rays, gamma radiation or similar Dermatitis caused by excessive exposure to radiation) is a treatment for neoplastic diseases. This is the most bothersome complication in patients and can lead to discontinuation of the procedure. Also, it is Feared occupations of medical personnel who perform radiation treatment and those who work at nuclear power plants It's also a disease. One of the most important differences is that cancer can develop from such exposure. It is. Burnt of all types is one of the most difficult conditions to treat.

The treatment of radiation dermatitis is described in the paper “A Ne” by Dr. Rafael Abad. w 5ubstance In The Treatment Of Radi odermatitis, Particularly of Neoplast ic Pati ■Shishigatana ARa (Mon-June 1967). Treatments include surgical, ultraviolet, infrared and such as those using red and red spectral lines, ultrasound, cyathylmy, and radar. Includes physical treatments as well as pharmacological treatments using inorganic, organic or biological products. be caught.

Physical treatments are of little value except as a supplement to another primary therapy, and are used only when the tumor has progressed. It is not recommended if it occurs in an area where Before using physical procedures , the risk of necrosis must be considered the most. Infrared and red spectral lines are Not used as it increases erythema. Ultraviolet rays were often used, but their preventive effects were UV radiation is no longer harmful, even though the lowest doses may be less painful. or not used. Radar can be used as an anti-inflammatory agent in very low doses. However, it causes vascular complications such as osmosis and sweating. It can be strained.

Many pharmacological treatments have been attempted. These treatments require large amounts of potassium iodide Oral administration of , topical acidified hydrogen peroxide to generate nascent iodine in situ administration, as well as paraffin, zinc stearate, zinc oxide, animal fats (e.g. , lanolin), petrolatum, and aloe vera plants. Topical treatments include ointments containing secretions. These treatments are non-specific. Most of them act simply as excipients. Local treatments often offer pain relief. anesthesia, antihistamines to reduce itching and redness, and Contains plant materials such as chlorophyll and chlorophyll. Penetration by hyaluronidase Other ingredients are used to increase the Also, vitamin H, vitamin A and D (halibut ointment), pantothenic acid alone or frozen Used in a dry mixture with trypsin, they have no disease-curing power. do not have. Sulfide-containing amino acids serve as radioprotective agents and regenerating agents for radiation damage. It is important. Cysteine and methionine are used both internally and topically. It is. Various hormones, such as insulin, adrenaline, thyroid drugs, Sex hormones, and heparin are used (topically). insulin and The use of epinephrine as a radioprotective agent is important because they increase susceptibility. is not desired. The use of cortisone (both topically and internally) is important . Substances such as nitrogen mustard and chloroquine have also been used but have been unsuccessful. It ended successfully.

Ionizing radiation, chemical agents (e.g. mustard gas or those used in chemical warfare) similar agents) and treatment of burns caused by thermal agents. Presents a similar problem. Products used to treat burns are non-specific. Most of them act simply as excipients. The product contains an embryo stimulant (blas tostimulins), chymotrypsin, trypsin, cortisone, punto Contains thenic acid and vitamins.

Ionizing radiation probably causes greater torpor (on the other hand, heat and Academic burns will cause necrosis. Repeated exposure to ultraviolet light may cause cancer ( (similar to cancer caused by low and repeated doses of ionizing radiation) will cause. Skin or mucinous cancers can develop with all types of burns.

However, the above measures were not sufficient. Therefore, effective therapeutic compositions, especially , reduces local reactivity, protects the skin or mucous membranes, reduces pain, and favors tissue regeneration. There is a need for compositions that remove cellular debris and prevent infection.

In particular, radioprotectants (i.e. it protects against radiation dermatitis) and radiation There is a need for therapeutic compositions that are repropellants. Similarly, another type of burn, It is effective in treating skin and mucous membrane damage caused by exposure to chemical agents. There is also a need for therapeutic compositions that can prevent skin cancer caused by exposure to ultraviolet radiation. It is said that Also used to treat abrasions, rashes, wounds, varicose ulcers, etc. There is also a need for compositions for. Additionally, wrinkled skin or stretch marks Composition for use in treating skin with stretch marks Things are also needed.

Many cosmetic treatments have been attempted. These procedures involve placing water on the skin. treatments with vitamins, embryonic, and placenta extracts.

The above measures were not sufficient. Therefore, regeneration acts as a biological coating. Action is required.

Summary of the invention The invention relates to compositions for use in therapeutic and cosmetic compositions, typically creams. A composition (hereinafter referred to as an active ingredient) is provided. The therapeutic composition is suitable for radiation skin treatment. To prevent inflammation and sunburn: abrasions, fraying, chapping, itching, diapers To treat rashes, eczema, dermatitis, and radiation dermatitis: and abrasions, burns (including radiation, chemical, and thermal burns); slow-healing wounds; and can be used to heal ulcers. The cosmetic composition nourishes the skin. It can also be used to treat wrinkles and stretch marks on the skin.

The invention also provides methods for obtaining the active ingredients and therapeutic and cosmetic compositions containing the active ingredients. A method of manufacturing a product is provided.

The active ingredient is derived substantially from secretions from physically stimulated living gastropods. Ru. Secretions are produced by mucinous, albuminous, and salivary glands. is a mixture of glandular secretions. Each secretion is responsible for a certain therapeutic effect. gastropod Secretions from the mucin or mucus glands in the feet have the effect of curing disease and promoting recovery. have fruit. secretion of the curvumin (protein) gland or 6 inside the body of gastropods provides antibiotic action in addition to disease-curing and recovery-promoting effects. gastropod Secretions from the salivary glands in the digestive system aid in the digestion of dead cells and in the deep skin. Provides digestive and osmotic effects, causing cleansing.

Upon physical stimulation, gastropods are stimulated by mucin, albumin, and salivary glands. Increases naturally produced secretions. Preferably, the physical stimulus centrifuges the gastropod. It is given by separating. The acceleration during centrifugation causes the snail to become Increases secretions from the Chin glands and also natural secretions from the albumin and mucus glands eject things.

The method used to obtain the active ingredient includes the following steps: (a) living physically stimulating the gastropod to cause fluid secretion; (b) producing the secreted fluid; (C) centrifuge the secreted fluid; (d) top Separate the clarity, (e) filtering the supernatant; and (f) Collect the filtrate.

Preferably, the gastropod is fasted for about 1-5 days 1-2 days prior to physical stimulation.

Fasting ensures that there are no toxins in the secreted fluid. fasting gastropods If not, the toxin may be present in the separated liquid; however, those skilled in the art The toxin can be inactivated using conventional methods known to those skilled in the art. Fasting is the material eaten by gastropods. Avoid toxins from food. One advantage of Kenpo is that animals can be used again. That is.

If the active ingredients are stored prior to use, the mixture is preferably kept at a temperature of about -10 to about -30°C. is rapidly frozen to approximately -20°C. Storage of large amounts of active ingredients or shelf life is one year or more, the mixture is then lyophilized. The active ingredient is Sensitive to heat, each glandular secretion denatures at approximately 70°C (+ or -10°C) .

If heated above 90°C, the regeneration of the active ingredient and the antibiotic effect will be lost.

Therapeutic and cosmetic compositions contain suitable amounts of active ingredients and biologically active ingredients. The novel excipients described below and their inclusion in therapeutic and cosmetic compositions Other commonly used ingredients may affect the stability and/or activity of the active ingredients and/or excipients. Contains other conventional ingredients if they do not adversely affect sex. Typically about 0°1 ~30-40% of active ingredient is used, preferably from about 0.5 to about 10%.

The amount of active ingredient used depends on the intended end use and also on the active ingredient of the liquid. Depends on whether you want to use lyophilized active ingredients or lyophilized active ingredients. In general, treatment Medical and cosmetic compositions used for prophylaxis as well as for treatment In each case, the same amount of active ingredient is used.

The manufacture of therapeutic and cosmetic compositions consists of excipients and active ingredients (unfrozen, pre-coated) (if frozen) at a temperature below 70°C. . One of the basic effects of such compositions is to protect the skin from damage. Current When using the composition, there is no difference in effectiveness based on age, race, or gender. set The composition remains stable from -20 to +70°C.

The use of therapeutic compositions is from about 0.05 to 0.5 g/cm", preferably about 0.1 g/cm”. It covers not only the skin but also the mucous membranes. For example, it can also be applied to the mucous membranes of the respiratory, digestive, urinary and genital organs. it is, Prevention and/or treatment of radiation dermatitis, as well as radiation dermatitis caused by exposure to solar radiation. Prevention of skin cancer caused by ionizing radiation, mustard gas, etc. All types of heat, including burns and injuries caused by medical and thermal agents Used to treat wounds and injuries. Similarly, it can cause dermatitis, eczema, diaper rash, To treat lentils: itching from insect bites and skin from photosensitivity Reduces and heals abrasions, fraying, sensitivity and chapped skin to reduce reactions. treat slow-healing wounds such as episiotomy, flank incision, and and also used to treat decubitus, atonic, and varicose ulcers can.

Immediate application of the therapeutic composition relieves pain and thus reduces the cost of burns. Primary shock (i.e., neurological system shock) can be avoided. When the composition is applied to a burned epithelial surface, Serous fluid loss caused by impairment to capillary permeability is prevented.

As a result of the application of the composition, statistically approximately The onset of secondary shocks, which account for 75%, can be avoided. The therapeutic composition was applied. After the itching, redness, and pain caused by the burn, apply and repair the epithelium. After that, it decreases and disappears in about 20 minutes, or in some cases at most 60 minutes. Ru. The composition has a clear antibiotic effect that prevents infection. It is antibacterial. It also has a deodorizing effect. There are no negative effects. The composition comprises a corticoid and It enhances the action of other drugs, such as antibiotics, thereby reducing their requirement.

When applied to burns in the form of a cream, it heals all without the use of anesthetics. Acts as a biological coating that eliminates pain from types of burns. cosmetic set The composition typically has a particle size of about 0.0f to 0.06 g/cm", preferably about 0.03 It is used applied in an amount of g/cm2. The composition is suitable for treating all types of damage to the skin. Can be used to repair scratches or damage. By using the cosmetic composition, The benefits provided by it are that it restores, regenerates, and protects the skin.

The composition is useful in facial creams and hand creams, especially for aging skin and Use in anti-wrinkle creams for abdominal or chest skin with stretch marks can. It is a moisturizing lotion, toning and cleansing liquid. , sunscreen cream, sunscreen tannin g) Can also be used in creams, deodorants and toothpastes.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is based on the observation of snail responses to ionizing radiation (X-rays or gamma rays). It was born out of research into biological behavior. Snails can perceive radiation and A large amount of viscous is produced as a defensive response, causing the stereotaxic organs to retract and protect themselves. secretes fluid. The snail changes its normal secretions as a means of protection. I assumed. However, electrophoretic analysis of the secretion shows that it is different from normally secreted mucus. It shows that there is no This fact, as well as the fact that this animal will never get a skin infection. The fact that this Attention was drawn to the problems associated with obtaining secretions in sufficient quantities.

Gastropods whose glandular secretions are used as active ingredients in the present therapeutic and cosmetic compositions are classified as Phylum Mo1lusca, and include limpets, rainbow limpets, as well as well-known varieties such as common snails and slugs. Therefore, it belongs to a large group of animals that promote nothingness. Shellless varieties can be grown on land or at sea. The shelled varieties, on the other hand, are called land or sea snails. Ru. Both He1ix and non-Helix varieties are suitable. It's about gastropods. For an extensive discussion, see Encyclopedia Br1tannica, Volume 10. , pp. 58-59 (1945): Invertebrate Zoolog y+ Volume 1, Porifera, Cn1daria, Platyhelm inathes, Aschelminthes, Mo1lu Karamo=A A nne[ida, and Re1ated Phyla, Alfred Kae stner, p. 594 (Robt, E., Kireger, Inc., Melbourne, FL, 1967); and Invertebr ate Zoology (5th edition), page 864, Robert D, B arners, (Saunders CoCo11e Publishing , IncA.

Troy, Missouri, +987).

Preferred gastropods include He1ix pomatia, He1ix hor tensis, He1ix nemoralis, He1ix cardi dula, 1(eljx tchthyomma(l(elix camp) ylea), ge1ix fructicicol (l (also called elix se uca),) lelix strigella, He1ix frut Amamo floating■ , He1ix bidens, He1ix arbostrom, )l elix rotundata, He1ix acule≠狽=A He1i x pulchella, He1ix personata, He1ix ho loserica, He1ix aperta, ) Ie Gokushu■@parna ssia, ) Ielix alonensis, 1 (elix candi dissima,) lelix pisana, and H■Pix gual teViana is mentioned.

The active ingredient is a biological product made by living gastropods of all types. It is. Used to obtain fluid secreted by living gastropods (secretions) The techniques used do not alter the biological structure of the products obtained from gastropods. centrifuging gastropods When separated, secretions are free of blood, kidney, lung or excreta or muscle contaminants. Not included.

The method used to generate the active ingredient is centrifugation. Examples include physical stimulation of gastropods, such as being rubbed. Another suitable, but preferred Other physical stimuli that can induce gastropods include sound vibrations, low high pressure, and low oxygen (i.e., acid). sterile) conditions, and exposure to thermal puncture. deemed inappropriate Physical stimuli include exposure to ionizing and ultrasound radiation. gastropod Extracting the composition using a chemical agent, e.g. a hypertonic solution, from the resulting secreted fluid It is inappropriate because the amount of is insufficient.

Centrifugation should be performed under conditions that do not destroy the shell of shelled gastropods. Ru. The shell protects the heart, and when the shell breaks, the heart is crushed and blood is drained from the heart. Liquid comes out. When using shellless gastropods, the Care must be taken to keep it alive and not crushed. Centrifugation of gastropods It must be done for a sufficient time and at a temperature and gravity (G) to cause the specimen to secrete liquid. Must be. The required rotation speed per minute (approximately 2000 to 4000 rpm) is , depending on the radius of the centrifuge arm. The larger the radius, the larger the circumference As a result, the acceleration becomes greater. Therefore, the required force is G force (i.e., the force of gravity speed). It is preferable to use a force of about 1 to 6 G for about 2 to about 10 minutes. Delicious. Most preferably, a force of 2 to 5 G is used. The force of about 7 to 8 G is the gastropod should not be used because it kills Centrifugation typically takes place between about 10 and 35°C. The temperature is preferably about 20°C.

In a preferred method, the centrifuge is accelerated to the desired rotational speed, decelerated, and accelerated again. . This is repeated for the desired number of pulsations. Several minutes (e.g. 3~ This pulsation is provided using a brake that contacts the shaft of the centrifuge every 4 minutes). typical Centrifugation is performed at 2G for 3 or 4 pulses for approximately 10 minutes. secretions , after separation from the living gastropod, this liquid was heated at about 200-5000 rpm for about 2 Centrifuge for ~10 minutes. The supernatant is then separated and contains approx. 1 to about 1 micron Filter through a pore filter with a certain pore size. Filtration is carried out under pressure to improve the filtration process. Speed can be increased.

Excipients selected for use in therapeutic and cosmetic compositions are and/or cosmetically acceptable form in which the therapeutic composition is used, e.g. Must be suitable for creams, gels, milk, oils, lotions, etc. The excipient is , has affinity for the skin, is well tolerated and safe. and suitable to provide the desired consistency and ease of application. Preferably, it is used in a sufficient amount.

For the preservation of biological substances and in dermatological and cosmetic procedures Excipients specifically selected for use are used herein. One of the advantages of this excipient One is to tolerate almost all other active ingredients and to The purpose is to provide stability. This preferred excipient has about 900-1300 min. Polyethylene glycol mixture, cetyl alcohol, glycerin with molecular weight range Lumonostearard selected mineral oils, calcium carbonate in fine powder form, fine powder form of zinc oxide, and an aqueous phase. The excipient may substantially contain from about 10 to 17%, preferably 12.0-15.5% cetyl alcohol and/or By-products such as laurate, myristate, and adipart: about 20 to 5 0%, preferably 30-50% polyethylene glycol mixture (e.g. mixture of ethylene glycol 400, 1500, and 4000): approximately 3°5~ 58%, preferably 4-6% glyceryl monostearade, about 7-12%, preferably preferably 8-10% mineral oil (preferably paraffin oil); about 5-8%, preferably is 5.5-7% calcium carbonate in fine powder form, about 0.3-0.6%, preferably 0.32-0.40% of zinc oxide in fine powder form; and an effective amount of typical consists of up to about 35% aqueous phase, preferably 16-30%. The amount of aqueous phase is , should be in an amount sufficient to obtain a composition of desired consistency. water If the amount of sex phase exceeds 35%, preservatives should be used. The aqueous phase is water, saline solutions [e.g., pyrogen-free 0.9% sodium chloride solution], and consists of physiological serous fluid. Percentages are based on weight and total 100%.

The percentages can be easily adjusted with minimal experimentation to achieve the desired creamy consistency. Can be provided. The excipient is odorless, white, and sensitive to UV, X-rays, and gamma rays. It doesn't resonate.

The above-mentioned excipients are obtained by melting cetyl alcohol by a laboratory method and adding polyethylene to the excipients. Add the glycol mixture and when the melting point is reached, pour the mixture into a commercial formulation. Galenic excipients prepared by transferring to a laboratory mixer It is. The second mixture is made by melting the glycerol monostearard and making a hot aqueous solution (80% "C). When the second mixture reaches the temperature of the first mixture, When reached, add the second mixture to the mixer. Calcium carbonate and zinc oxide fine powder and mineral oil are added with continuous stirring. The resulting excipient is white Color, odorless, and stable. The excipients include cream, milk, pomade, etc. Can be used for manufacturing. Even when used over long periods of time, the excipients No harmful effects. The excipient may cause any adverse reaction, e.g. allergy. It also does not cause toxic or carcinogenic effects. The excipient allows the active ingredient to pass through the skin. Promotes absorption. It does not break down between -20 and +70"C and is and can be used in many extreme climatic conditions. Also , it is produced by decimeter waves, ultraviolet rays, 1.3 MeV gamma radiation, and photons. It is not affected by this. The excipient is also unaffected by the container in which it is stored. stomach. The importance of this excipient is not based on any particularly unusual ingredients, but rather in numerous experimental formulations. It is based on their ratio which is the result.

Any compound that can be used in the therapeutic composition when the aqueous phase is greater than 35% Ingredients include preservatives such as methylparaben and sodium bisulfite. Oxidation inhibitors and other ingredients commonly included in therapeutic compositions include Ru.

In the cosmetic composition, paraffin oil, turtle oil, or mineral oil, such as another oil, in an amount of about 1 to about 10%, preferably about 2%; boric acid; , about 0. Chlorophyll in an amount of 1 to about 0.6%, preferably about 0.3%: Formol (30%) in an amount of 0.25 to about 1.5%, preferably about 1%, about 0 ．． Glycerin in an amount of 3 to about 3%, preferably about 0.4%; about 0.1 to about 4%; , preferably about 0.5%, and heparin at about 0.01 to about 0.5%. 4%, preferably lanolin in an amount of about 0.1%; 1 to about 6%, preferably about 0. 5 %, menthol in an amount of about 0.25 to about 2.5%, preferably about 1%; Pantothenic acid at a concentration of about 0.01 to about 0. 5%, preferably about 0. In an amount of 1%; Potassium aluminum sulfate is added at a concentration of about 1.5% to about 1.5%, preferably about 0.0%. 4% of in an amount of about 0.01% to about 0.03%, preferably about 0.03%; Min C in an amount of about 0.01 to about 0.5%, preferably about 0.2%, and a metal Iodine, about 0. It can be used in amounts of 1 to about 1.1%, preferably about 0.6%.

The percentages mentioned above are based on weight, with the total weight of the cosmetic composition being 100%. Ru.

Pantothenic acid and heparin are typically used in nourishing facial creams : Glycerin and lanolin are used in nourishing hand creams : and lanolin Norrin and potassium sulfate are typically used in clarifying and moisturizing fluids.

Potassium aluminum sulfate is used in toning and cleansing fluids, and also , boric acid and sulfuric acid steel are added. Boric acid, methanol, chlorophyll, and and formol (30%) are used in mild body deodorants, Only boric acid is a mild intimate deodorant. used inside. No optional ingredients are used in sunscreen creams, but Metallic iodine and vitamin C are added to sunscreen creams.

The activity of the therapeutic composition is evaluated using rats. Ultraviolet light on both flanks of the rat The radiation is delivered in an amount sufficient to cause erythma. One side is treated and the other flank left untreated as a control. In the same way, rats X-rays are administered using a radiotherapy device and directed guidelines.

To assess the radiation protective ability of the composition, approximately 0.1 g/cm'' of the composition was irradiated. Irradiation is carried out in increasing doses, applied to the area to be irradiated. Emissions exceeding typical amounts Should additional doses of radiation be given before radiation dermatitis occurs and is observed? I'll come. If the therapeutic composition is applied before starting irradiation, the dose is about 3 5-45%, and without administration of the therapeutic composition, the irradiation could be increased by 1000c. Can't go beyond Gy. If necessary, a conventional dose of 5000-6000 cGy, Increased to 7000CGy, or may be much larger. .

One of the advantages of the cosmetic composition is that it can be applied to any type of skin, It can be used by both sexes. The composition contains fragrances that have no inherent adverse effects. You can do it. When applied, the composition causes a pleasant feeling . The effectiveness of the cosmetic composition was evaluated by wrinkle reduction and skin regeneration. Ru.

The methods described above may be modified by those skilled in the art without departing materially from the scope of the invention. It will be appreciated that numerous changes may be made. Such changes will be obvious to those skilled in the art. However, it is within the scope of the present invention.

In this example, the active ingredient used in the therapeutic composition (often referred to as the base agent) Explain the manufacturing process.

A total of 2 kg of snails (Helix hortensis) were fasted for 2 days. After that, place it in a centrifuge tube at 10100O. Snails at 10-25℃ Centrifuged at 2G for 1G. Remove the snails that are still alive and secrete the glands. 800 g (800 ml) of the product was obtained.

Glandular secretions were centrifuged at 200 Orpm to sediment large particles. De-liquid cant and at the lower end, a Millipore filter with a pore size of about 0.1 to about 1 micron. - into a cylinder equipped with. Cylinders are used to facilitate filtration. It was sealed with a lid connected to a compressed air system. Total of 600g (600ml) The filtrate (ie, active ingredient) was collected.

Example 1 construction The procedure of Example I was repeated. However, a pulsating effect was used to increase the amount of glandular secretion. centrifugal The separation is performed by accelerating to 2G, holding this force for 10 minutes, decelerating to 0.5G, and applying this force to 2G. Perform by holding for 0 seconds and repeating this procedure 4 times, then centrifuge. and removed live snails. Total wire drawing of 800-900g The output was obtained by centrifugation of the gastropod at 2000 g. 800g in total < 800 ml) of filtrate (ie active ingredient) was collected.

Example III In studying glandular secretions, elementary Another was carried out using a cation exchange resin. Various amino acids and their therapeutic value The presence of a non-toxic substance with no value was indicated. The main groups of amino acids include: It was.

Group ■ - Amino acids with side chains corresponding to about 20-30% of the total amino acid content No acid di GELUP TI - Hydroxyl (- Amino acids having an OH) group Group lll - Thio-thiol in the side chain, corresponding to about 10-13% of the total amino acid content (-3H) group-containing amino acid Geloop IV - dicarboxylic acid groups corresponding to about 23-27% of the total amino acid content an amino acid having; Group V - with diamine groups corresponding to about 8-12% of the total amino acid content amino acid; Group Vl - with aromatic groups corresponding to about 12-16% of the total amino acid content amino acids, and Group vII - imino acids representing about 4-5% of the total amino acid content.

Group I is about 13.33% isoleucine, about 13.33% leucine, about Contains 13.33% alanine, about 20% valine, and about 40% glycerin. I was reading. Group II is about 30-40% threonine and about 60-70% Contains serine. Group I11 has about 80-90% cysteine and about It contained 10-20% methionine. Group TV each has about 50% of the audience. Contains spartic acid and glutamic acid. Group ■ is approximately 66% Algi It contained about 33% seaweed and seaweed. Group Vl each has approximately 50% Contained phenylalanine and 1,000 rosin. Group Vll only has proline It contained.

The secretion contains 8 of the 10 amino acids essential for human metabolism and survival. It was. Within this group, only histidine and tryptophan are observed. Examples of preferred excipients for use in therapeutic compositions containing active ingredients Explain the manufacturing of

Heptyl alcohol (15 g) was melted using standard methods and then added to polyethylene glycol. Coal [polyethylene glycol 400 (49,%), 1500 (1,0%) Add 50 g of a mixture of Oyobi 4000 (49.5%)] and mix it with the first mixture. did. Once the melting point was reached, the mixture was transferred to a commercially available dispensing laboratory mixer. .

The second mixture was prepared by melting 5 g of glycerol monostearard and preliminarily adding 80" Prepared by adding 12.6 g of heated distilled water or preferably physiological serum to C. .

After making the temperature of this second mixture the same as that of the first mixture, was added to the first mixture. While continuously mixing, add 7 g of calcium carbonate and and 0.4 g of zinc oxide, both in the form of fine powder, and a small amount of paraffin. oil (10ml) was added.

Deaf In this example, (i) treat all types of burns, including thermal burns and chemical burns; (11) to prevent or treat radiation dermatitis; and (11) to prevent or treat radiation dermatitis. iii) describes the production of therapeutic creams useful for preventing or treating sunburn; I will clarify.

A total of 25-30 ml of liquid secretion (or 25-30 g of lyophilized secretion) ) with 500-600 g of the excipient of Example IV (i.e. physiological serum). (prepared excipients) and mixed in a mixer at 30-40"C. Total of 500 ~700g of cream was obtained.

palanquin ± This example describes animal studies using the therapeutic cream of Example V. Formation of Example IV A control containing only the drug was used.

The back of a previously depilated rat was s With the RT-100 device, the source and skin were Irradiation was performed using a single dose of y.

After irradiation, only 1-2 g of excipient per 4.9 cm was administered daily to 106 rats. The therapeutic cream was applied daily to the control group and to the test group of 112 rats. Applied.

Healing of radiation dermatitis in rats was observed. Below is the percentage of animals that do not heal. Shown below.

Excipient alone; Active agent and excipient containing Ichinoichi; Untreated animals; Treated animals. Animals treated with therapeutic cream 1 week later 100% 100% 100% 2i ! After I 99915 90% 90% 3 weeks later 99% 85% 80% 4 weeks later 95% 80% 71% After 5 weeks 92% 77% 61% After 6 weeks 90% 76% 31% After 7 weeks 89% 75% 10% After 8 weeks 85% 75% 2% This result indicates that the cure provided by the excipient is minimal and likely that the healing effect provided by the therapeutic cream is solely due to its insulating effect; This shows that it is very effective and is due to the active ingredient (base ingredient) in the cream. In this example, the therapeutic cream of Example V was used to protect against radiation dermatitis. Describe the results of clinical trials in people with cancer.

Apply therapeutic cream (0.1 g/10 cm") to the skin area to be irradiated for 2 Applications were made at 4 hour intervals. Half of the patients were treated with the cream and the other half were treated with the cream. There wasn't. After irradiation with I,000 cGy, lesions occurred in untreated patients. Cree In patients treated with this system, by the time radiation dermatitis developed, the protected area had increased to 7000 ~8000 cGy was irradiated. This corresponds to an increase in dose of approximately lθ~25%. Ru.

In untreated patients, radiation dermatitis is approximately 40-50 Gy (Gy = gray - units used to measure radiation). In treated patients, skin The maximum limit of tolerance increased approximately togy without radiation dermatitis appearing. therapeutic chestnut The application of the cream lasted approximately 30-45 days after irradiation was stopped.

Example Vllll In this example, Example V describes the results of a human clinical trial using a therapeutic cream.

Apply the therapeutic cream to the affected area in an amount of 0.1g/10cm” per day. used. The results are shown below.

Necessary for healing from radiation dermatitis Affected area Average number of days Mammary ridge 14,4 Scar after breast amputation 22.9 Axillary fossa 24.5 Due to previous infection 74.8 worsened area The decline in the number of patients with radiation dermatitis of the mammary crest began on day 17. radiation dermatitis was virtually eliminated by day 11. Increased swelling from previous surgery as a result of breast amputation Radiation dermatitis that occurs over the scar and takes much longer to heal. It was. The decline in the number of sick patients began on the 16th day. Approximately 50% of patients remain on the 23rd day I was completely healed. Healing for all occurred on day 28. The number of patients with axillary radiation dermatitis Decline began at day 18 and radiation dermatitis was cleared by day 28.

There is a period of epithelialization that determines the period until the onset of healing, but itching and burning A sensation of burning pain--which makes almost every area In cases where the patient is unable to sleep without pain relief, relief occurs only after treatment begins. It happened a few hours later.

If radiation dermatitis is exacerbated and further aggravated by other methods, initial healing may not be achieved. It took a long time.

In thoracic radiation dermatitis (79 patients studied), healing occurred on days 19 and 22. 91.1% of patients developed rapidly between the eyes and healed between the 25th and 28th day. Reached. After 2.5 weeks, 25% of patients were initially cured. After 3 weeks, 50% of patients was cured. All patients were cured after 4 weeks.

21 patients treated for acute radiation dermatitis in the anterior and posterior regions of the abdomen (including the crotch) In patients, healing began in the first week. By day 12, 50% of patients was cured, and all patients were cured in about 208 eyes.

In cases of radiation dermatitis and radiation cellulitis, healing times were much longer for 12 patients It was. After 17 weeks, the extremely bothersome itching symptoms were alleviated. epidermis and dermis The area has returned to normal, but there is still the appearance of connected trauma caused by skin contraction. It existed. The patient has dry, rough, relatively sensitive skin. there was. Therefore, a minimum of several months of medical care should be considered.

In cases of chronic radiodermatitis, where symptoms begin 1 to 15 years after treatment, many deficiencies can occur. The lesions probably cannot be improved other than by surgery and may cause itching and/or burning. If the pain can be alleviated by treatment with the therapeutic cream, There is.

The soured skin area, approximately 20 x 20 cm, took approximately 3 weeks to heal.

Thermal burns, chemical burns, and radiation dermatitis burns heal in approximately the same amount of time. Ru. The patient does not require analgesics (the patient does not suffer from pain) or antibiotics and can be taken home at home. It can be treated with If a large area of skin is burned, the patient should be filled with cream. It is preferable to cover it with a soft sheet. For recovering sunburn, the active ingredient will last for 3-5 days. Overuse.

Example IX This example shows a nourishing facial cream for use on normal, dry or oily skin. Describe the manufacturing of the system.

The cream contains 200 g of the excipient of Example TV, 10 ml of active ingredient, and 0° pantothenic acid. 2g of heparin, and 02g of heparin.

The cream tones and revitalizes the skin. Active ingredients repair epithelium and rejuvenate skin let The cream also serves as an exfoliate, Removes external dead skin N (epithelial corneal layer) and promotes new skin growth. pa Use of ntthenic acid and heparin in creams is optional but preferred . Because they enhance recovery and osmotic action.

Example X In this example, nutrition/XX used for dry, normal or oily skin. Explain the production of Todream.

The cream contains 100 g of the excipient of Example IV, 5 g of active ingredient, glycerin 4C1 and Produced by mixing 0.5 g of lanolin.

The resulting cream is very smooth and spreads well. The cream can also be used during the day. Can be applied at night to regenerate, restore and smooth the skin.

Example XI In this example, we will discuss the preparation of clarifying and moisturizing liquids for dry, normal or oily skin. Explain the structure.

For use on normal and oily skin, vaginal fluids are mixed with 200 g of the excipient of Example IV, 20cc of active ingredient, 0.3g of potassium aluminum sulfate, and rose water +0cC manufactured by mixing.

For use on dry skin, vaginal fluids should be supplemented with 2 cc of mineral oil, e.g. paraffin oil. prepared as described above, except that: Colorants can be added but are preferred. It's not right. This is because they can be intolerable and toxic.

The resulting liquid cleanses and smoothes the skin, increasing the clarity of the complexion. The liquid is Useful as a base for makeup (e.g. powder). It's makeup The harmfulness of powders - which consist of minerals with a hardness value of 1 on the Mohr scale Protects the skin from harmful effects.

Example Xll This example describes the production of toning and cleansing liquid.

The solution contained 100 g of the excipient of Example IV, 10 cc of active ingredient, 100 c of physiological serum. c, potassium aluminum sulfate 0.3g, boric acid 0. 5g, and sulfuric acid steel 0. Prepared by mixing 1 g.

Vaginal fluid is recommended for use on delicate or acne-prone skin . The liquid causes a strong sense of refreshment and a calming, restful feeling. vinegar.

Example XIII This example describes the production of an anti-wrinkle cream.

A cream for daily use was prepared using 250 g of the excipient of Example 1v, 5 cc of active ingredient, Produced by mixing 7g of Norin and potassium aluminum sulfate 156g can be added.

The concentrated cream, used once a week, contains 15g of active ingredient, 15g of lanolin, and sulfur. The process was prepared as described above, except that 2 g of potassium aluminum acid was used. The cream is easy to apply (and is used only on wrinkled areas; the active ingredients are: Although effective in reducing wrinkles, other ingredients cause an astringent effect.

The concentrated cream was tested on more than 200 people. First, apply the cream. , apply to half of the face, then apply to the other half of the face. The effect is that each Lasted about a week after application. The more and bigger the wrinkles, the more visible the treatment The effect will also be greater.

Example XIV This example describes the production of deodorant cream. Use on armpits and feet. A mild body deodorant for use contains 100 g of the excipient of Example IV, 10 cc of active ingredient, 1 g of boric acid, 1 g of methanol, 1 g of chlorophyll, and 1 g of chlorophyll. Produced by mixing 5 cc of Amol (30%).

A mild intimate deodorant for use in pottery areas is Example III By mixing 100 g of excipient, 10 cc of active ingredient, and 0.5 g of boric acid. Therefore, manufacture.

The resulting deodorant cream is easy to apply.

Example Xv This example describes the production of sunscreen cream. Sunlight causes a series of lesions on the skin - It is initially a precancerous lesion (e.g. seborrheic, keratosis, or actinic keratosis) , many of which can later become cancer (epithelial tumors).

A sunscreen cream is prepared by mixing 250 g of the excipient of Example IV and 5 cc of active ingredient. Manufactured by

Avoid sunburn, suntan cream contains 1g of metallic iodine and 0.3g of vitamin C. Manufactured as described above except for the following.

Applying a thin coat of sunscreen once before exposure to sunlight is sufficient for prevention. It's a minute. If you get sunburn, apply a thin coat of the cream every 6 hours. should be used.

The sunscreen cream was used to treat 306 fair-skinned individuals.

The product was used prophylactically in 6% of patients and therapeutically in 94% of patients. Ta. To avoid sunburn, swim in a swimming pool with highly chlorinated water - where the subject can form blisters. (phlytena) - tanned people and seaside It was used to treat people who suffered from sunburn. In each case, the cream relieves pain and burning. The stinging sensation disappears within seconds of application and blisters disappear within 5-6 hours. It disappeared and the tan was gone in 24 hours.

Having described the preferred embodiment of the invention in detail, various changes and modifications thereto may be disclosed. The quality will be readily apparent to those skilled in the art. Accordingly, the spirit and scope of the invention is , shall be limited only by the claims, not the specification. I haven't come to be able to do it.

,,-1,,,N, PCT/11592101334 International Search Report Continuation of front page (51) Int, C1,5 identification symbol Internal office reference number A 61 K 7/48 9051-4C71509283-4C CO7K 3102 8318-4H 151088318-4H (81) Designated countries EP (AT, BE, CH, DE.

DK, ES, FR, GB, GR, IT, LU, MC, NL, SE), AU, BR ,CA,C8,HU,JP,NO,PL,RU I

Claims (1)

[Claims] 1. an active substance consisting essentially of secretions from physically stimulated living gastropods component. 2. Glandular secretions from the mucin, albumin, and salivary glands of living gastropods The active ingredient according to claim 1, which is a mixture of. 3. The gastropods are Helix pomatia and Helix pomatia. Helix nemoralis, Helix calgis Helix carudidula, Helix carudidula x tochthyoma), Helix fructicicola (Helix f) ructlcicola), Helix strigella elia), Helix fruticum, Helix Helix bidens, Helix alpostolum (Helix arbostorum), Helix Rotundata (Helix rotundata), Helix aculea ta), Helix pulchelia, Helix Helix personata, Helix holocerica (Helix holoserica), Helix aperta (Helix aperta), Helix pamassia, Heli xalonensis, Heli xalonensis Helix candidissima, Helix pisana (Helix pisana), and Helix guarteviana (Heli The activity according to claim 1, selected from the group consisting of component. 4. 2. The active ingredient according to claim 1, wherein the secretion comprises amino acids. 5. 2. The active ingredient according to claim 1, wherein the secretion comprises amino acids and non-toxic substances. 6. Amino acids include isoleucine, leucine, alanine, valine, glycine, and onine, serine, cysteine, methionine, aspartic acid, glutamic acid, Claimed to contain luginine, lysine, phenylalanine, tyrosine, and proline Active ingredient according to item 4. 7. Amino acids include isoleucine, leucine, alanine, valine, glycine, and Onine, serine, cystine, methionine, aspartic acid, glutamic acid, alkaline Claims containing genin, lysine, phenylalanine, tyrosine, and proline 5. The active ingredient according to 5. 8. (a) Physically stimulate a living gastropod to cause fluid secretion; (b) ) separating the secreted fluid from the living gastropod; (c) centrifuging the secreted fluid; separate, (d) separating the supernatant from the particles; (e) filter the supernatant, and (f) Collect the filtrate The active ingredient produced by the process. 9. Fasting the live gastropod before the step of physically stimulating the live gastropod 9. The active ingredient according to claim 8, further comprising the step of causing. 10. (a) Physically stimulate a living gastropod to cause fluid secretion ( b) separating the secreted fluid from the living gastropod; (c) separating the secreted fluid from the living gastropod; separate the heart, (d) separating the supernatant from the particles; (e) filter the supernatant, and (f) Collect the filtrate manufacturing active ingredients for use in therapeutic or cosmetic compositions, including the process how to. 11. Prior to the process of physically stimulating the gastropods, the process involves fasting the living gastropods. 11. The method of claim 10, further comprising the steps of: 12. 12. The method according to claim 11, wherein fasting is performed for up to 5 days. 13. The physical stimulation in step (b) is sufficient to cause the gastropod to produce the secreted fluid. Claim 10: carried out by centrifuging the gastropod for a period of time and under gravity. Method described. 14. Centrifugation is performed in a pulsatile manner by continuously accelerating and decelerating the centrifuge. 14. The method of claim 13, wherein: 15. Gastropods are fasted for up to 5 days and physical stimulation causes gastropods to 11. The step of claim 10 is carried out by centrifugation at about 6G for about 2 minutes to about 10 minutes. How to put it on. 16. The gastropods are fasted for about 1 to about 2 days, and the centrifugation is performed continuously using a centrifuge. 16. The method according to claim 15, wherein the method is carried out in a pulsatile manner by accelerating and decelerating. 17. The centrifugation of step (d) is performed at about 200 to about 5000 rpm. The method according to item 10. 18. The filtration in step (f) uses a pore membrane having a pore size of about 0.1 to about 1 micron. 11. The method according to claim 10, wherein the method is carried out using 19. 19. The method according to claim 18, wherein the filtration is carried out under reduced pressure. 20. 11. The method of claim 10, further comprising freezing the filtrate. 21. 11. The method of claim 10, further comprising the step of lyophilizing the filtrate. 22. an effective amount of the active ingredient of claim 1 and an effective amount of substantially about 10 to 1 7% cetyl alcohol, about 4-6% glyceryl monostearate, about 20- 50% polyethylene glycol mixture with a molecular weight of about 900-1300, about 7 ~12% mineral oil, about 5-8% calcium carbonate in fine powder form, about 0.3-0. An excipient consisting of 6% zinc oxide in finely divided form and an effective amount of an aqueous phase, with the proviso that (Percentages total 100% by weight). 23. an effective amount of the active ingredient of claim 8 and an effective amount of substantially from about 10 to 17% cetyl alcohol, about 4-6% glyceryl monostearate, about 20% ~50% polyethylene glycol mixture with a molecular weight of about 900-1300, about 7-12% mineral oil, about 5-8% calcium carbonate in fine powder form, about 0.3-0 6% zinc oxide in fine powder form and an effective amount of an aqueous phase up to about 35%. (wherein percentages total 100% by weight) thing. 24. The amount of active ingredient is about 0.1 to about 30% based on the total amount of the composition; and the amount of aqueous phase is about 16-30%. 25. If the excipient is a cream, pomade, amble, gel, milk, oil, or 24. The composition of claim 23, which is in the form of a composition. 26. about 45 to about 95% excipients, about 5 to about 25% active ingredient, about 0.01 to about A beauty product containing 0.5% pantothenic acid and about 0.01 to about 0.4% heparin. 23. A composition according to claim 22 for use as a facial cream. 27. about 45 to about 95% excipients, about 5 to about 25% active ingredient, about 0.1 to about 4 % glycerin and about 0.1% to about 6% lanolin. 23. A composition according to claim 22 for use as a. 28. about 45 to about 95% excipients, about 5 to about 25% active ingredient, about 0.1 to about 6 % lanolin, and about 0.1 to about 1.5% potassium aluminum sulfate. 23. A composition according to claim 22 for use as an anti-wrinkle cream. 29. about 45 to about 95% excipients, about 5 to about 25% active ingredient, about 0.1 to about 0 6% boric acid, about 0.25 to about 2.5% methanol, about 0.25 to about 2.5% of chlorophyll, and about 0.3 to about 3% formol (30%). - A composition according to claim 22 for use as a deodorant cream. 30. about 45 to about 95% excipients, about 5 to about 25% active ingredient, and about 0.1 Contains ~0.6% boric acid, used as an intimate deodorant cream 23. The composition according to claim 22, for use in 31. about 45 to about 95% excipients, about 5 to about 25% active ingredient, and optionally about 0.1% to about 1.1% metallic iodine and/or about 0.01% to about 0.5% 23. Comprising vitamin C, for use as a sunscreen cream. Composition of. 32. about 45 to about 95% excipients, about 5 to about 25% active ingredient, about 0.1 to about 1 A common solution containing 5% potassium aluminum sulfate and about 20 to about 50% rose water. For use as a cleansing and moisturizing liquid for normal or oily skin. 23. The composition according to claim 22. 33. about 45 to about 95% excipients, about 5 to about 25% active ingredient, about 0.1 to about 1 5% potassium aluminum sulfate, about 20 to about 50% rose water, and about 1 to about Requested for use as a cleansing and moisturizing liquid for dry skin, containing 10% oil. 23. The composition according to claim 22. 34. 34. The composition of claim 33, wherein the oil is paraffin oil or turtle oil. 35. about 45 to about 95% excipients, about 5 to about 25% active ingredient, about 20 to about 50% % water or parawater, about 0.1 to about 1.5% potassium aluminum sulfate, about 0 Toning comprising 1 to about 0.5% boric acid and about 0.01 to about 0.3% copper sulfate and a composition according to claim 22 for use as a cleansing liquid. 36. The excipient is comprised essentially of about 12.0-15.5% cetyl alcohol, about 3% 0-50% polyethylene glycol mixture, about 4-6% glyceryl monoester Alert, about 8-10% mineral oil, about 5.5-7% calcium carbonate, about 0.32 ~ about 0.40% zinc liquefied and about 16-30% water, saline solution, and 24. The composition of claim 23, comprising an aqueous phase selected from the group consisting of physiological serum fluids. 37. (a) an effective amount of substantially about 10-17% cetyl alcohol, about 4-17%; 6% glyceryl monostearate, about 20-50%, molecular weight about 900-1 300 polyethylene glycol mixture, about 8-10% mineral oil, about 5-8%, Calcium carbonate in the form of a fine powder, about 0.3-0.6% zinc oxide in the form of a fine powder, and an effective amount of an excipient consisting of an aqueous phase (where percentages are based on weight and total 10 0%); and (b) adding an effective amount of the active ingredient according to claim 1 at a temperature below 70°C; A method of manufacturing a therapeutic or cosmetic composition, comprising: 38. A therapeutically effective amount of the composition of claim 22 in cream form is applied to the skin or mucous membranes. before or after exposure to a radiant energy source, or any chemical that causes burns. Radiation skin therapy, which involves topical application before or after exposure to medical or thermal agents. Methods of preventing dermatitis and treating burns. 39. Claim 3, wherein the cream is applied in an amount of about 0.1 to about 0.5 g/cm2. 8. The method described in 8. 40. Claim 38, wherein the mucous membrane is respiratory, digestive, urinary, or genital mucosa. Method described.