TW464509B - A pharmaceutical composition for ameliorating a cellulite condition - Google Patents

Abstract

New topically applied treatments for cellulite are shown by comparative data to effect structural improvements in cellulite-afflicted thigh area tissues including skin-thickening, thigh-firming and thigh-reduction. The disclosed treatments disrupt the skin's water barrier and elevate trans-epidermal water loss (TEWL) for extended periods of weeks or months and include methods of mechanical or solvent action, for example, tape stripping, or acetone washes. Preferred treatments use creams with active ingredients such as lactic acid to elevate TEWL, a retinoid, preferably vitamin A palmitate to disrupt barrier rebuilding and prolong elevation of TEWL levels, and a cerebroside to inhibit lipid synthesis and intensify the TEWL elevation. Diuretics, for immediate esthetic improvements, anti-irritants and anti-oxidants for irritation control are optional ingredients.

Description

A7 B7. Step-Ministry of Central Standards Bureau J-Consumer Cooperative Printed 464509 V. Description of the Invention (i) The present invention relates to the topical application of sebum granules, including the composition and method. For long-term use, such as daily application and For several months, a structural improvement in the condition of sebum particles can occur. The term sebum granules refers to the abnormal accumulation of a large number of fat cells under the skin, which results in unsightly local visual discontinuities on the skin surface. Sebum is a term coined by Nicole Ronsard in the 1970s (see Webster's New Universal Unabridged Dictionary, 2nd edition, Dorset Baber i983). It is used to describe the abnormal smooth accumulation of abnormal fat masses and the smooth curve of the skin. Extensive phenomena of estrangement. Physiologically, sebaceous granules are degraded by microcirculation in the body where fat accumulation occurs. Severe sebaceous granules are characterized by the degradation of subcutaneous blood vessels, poor blood flow, thinning of the epidermis and dermis of the skin, the appearance of hard masses of fatty substances surrounded by protein in the subcutaneous area, and the storage and accumulation of body fluids. The result is an "orange peel" -like appearance on the skin. Sebum particles most often cause problems in the thighs, buttocks, and upper arms, and are less common in the extremities, back, trunk, and center of the corpus callosum, as well as on the face, neck, hands, and feet. Sebum particles are often associated with obesity, but they also appear on the skin of individuals of normal or near-normal weight. It is more common in women than in men, and it is more common in Caucasians than in darker-skinned individuals. Due to the serious damage to the appearance of individuals, the skin granules have far-reaching psychological effects, hurt the self-esteem of the affected individuals, and are not conducive to the healthy psychological development of young men and women. Therefore, there is a great need for effective treatment of sebum particles. Known methods for treating sebum granules include local mechanical action, local application of paper waves, general Chinese standard (ΓΝ5), Λ4 size (210X297 cm), (please read the note on the back, and then fill in this page)

* 1T ^ 464509 Α7 Β7 5. Description of the invention () Use of chemical agents, exercise, diet adjustment, and a combination of these treatments. An effective treatment is a combination of diet and lotus movements that is actively maintained for a long time. Many people seek easier treatments. From the clinical trials described here, it is clear that the known simple topical treatment methods only provide surface efficacy and do not significantly improve structural defects.

Stewart, U.S. Patent No. 4,829,987 teaches a method for treating sebum granules in which a mineral solution-soaked wrapping tape is applied to an appropriate body part, and then the part is passively moved. This treatment is inconvenient or too cumbersome for many people. Massage can improve withdrawal and stimulate peeling, smooth the skin surface and increase blood flow, but only temporarily. U.S. Patent No. 4,0,922 from Henderson discloses a facility and method for treating sebum granules. The facility includes multiple elastic balls that can be applied to the affected body parts. Heat therapy can also stimulate microcirculation and provide short-term benefits, but without long-term structural improvements. Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) Body lotions, medicaments and creams contain rumored active biological ingredients, such as golden gooseberry, gorse, horse chestnut, class M, Seawater or aesculin can provide short-term, lightly withdrawn microcirculation, but at most it is only moderately active. The aforementioned massages, heat treatments and biological formulas do not take into account issues such as renewal of skin concerns, fat metabolism, accumulation of body fluids or degradation of blood vessels. Diuretics, which are usually plant-based, promote lymphatic exudation and produce good short-term symptoms without taking into account long-term skin defects, fat metabolism or vascular degradation. This paper scale is applicable to China National Standards (CNS) A4 specifications (210 × 297 mm) printed by the Central Standards Bureau Shoulder Workers Consumer Cooperatives 5 45 0 9 a? __B7 ............ ....... ^ V. Description of the invention (3) Caffeine I, theophylline and other xanthines, appear to be effective as diuretics and to promote fat metabolism at high concentrations. Aminophylline is currently

A popular active ingredient known as thigh cream or thigh smoothing cream appears to be effective as a strong diuretic to promote lymphatic drainage, but has been reported to have significant toxic side effects (see Merck Index, 11th Edition) , Merck & Co. Inc. 1989 Monograph No. 477). These agents do not take into account structural defects in the skin and blood vessels.

U.S. Patent No. 5,030,451 to Trebosc et al. Describes some cosmetic compositions containing an improved caffeine derivative as an active agent. According to Trebosc et al., Column 9, lines 15-20, the disclosed formula has "good and long-lasting 'fat-breaking properties'" and thus has proven very effective in slimming programs and treating sebum particles. &Quot; However, No valid data have been reported. In column 1, lines 61-65 > Trebosc et al. Taught the faster rate of subcutaneous penetration and confirmed the superiority of these agents in treating sebum particles.

Mausner U.S. Patent No. 5,21 5,759 refers to the use of methylsilanol theophylline acetate alginate and methylsilanol mannuronic acid for the activity of preventing sebum granules. Without descriptive disclosure, the effects of such substances are assumed to be equal to diuretics. One disadvantage of marketing stimulant compositions (containing caffeine, aminophylline or related agents as active ingredients) for the treatment of sebum granules is that medication problems will prevent them from being included in pharmacies for sale Cosmetic composition. Prolonged reuse may cause harmful side effects, and government regulations may limit marketing. Another disadvantage is that this kind of medicine _____ _ 6 ". _ This paper size is applicable to Chinese national standard _ (CNS) M specifications (2ΙΟχ: 297 g 漦) (Please read the precautions on the back before filling this page), 1Τ 4 5 45 0 9 A7 B7

Llti Department of Economics and Social Affairs, Consumer Affairs Cooperative of the Central Bureau of the People's Republic of China, Printing Co., Ltd. V. Invention Description (The agent does not take into account the structural problems of skin and vascular defects. Scrub particles act mechanically, remove the outer layer of treatment, smoothen the treatment surface, and stimulate treatment updates. However, it fails to promote lymphatic drainage, long-term microcirculation degradation or fat metabolism. Scrub particles are hard particles, usually suspended creams or gels, which are rubbed or massaged to achieve mechanical exfoliation. The particles are usually Polyethylene balls, however, natural particles such as crushed peaches or apricot kernels have also been used. The disadvantage of these products is that it is difficult to control allergies. Topical retinoids, such as US Patent No. 5,051,449 to Kligman It can improve sebaceous granules to a limited extent. Kligman has published a qualitative report comparing the efficacy of a topical retinoic acid formula with an unnamed non-medical cream after more than 6 months. The efficacy includes skin thickening , An increase in the number of new blood vessels, and an observed moderate to significant improvement using the pinch test (column 6, lines 50-61). Nothing was provided Quantitative data, so skilled artisans cannot determine the value of Kligman's sebum treatment. Many people expect and expect sebum treatment to be more effective than moderate improvement after 6 months of treatment. Retinoids must be limited Acid concentration to avoid allergies (see column 2 of Kligman, lines 59-60) and therefore cannot achieve sufficient efficacy by increasing the dosage • The retinoic acid treatment method does not provide a satisfactory long-term treatment of sebum particles, and A more effective topical treatment is needed. Contrary to Kligman's unfounded induction, my quantitative clinical research found that after 3 months of daily treatment, retinoic acid did not cause significant skin thickening. Therefore, there is a need for an easy-to-apply sebum treatment that can provide structural improvement within a reasonable time. This paper is scaled by Shizhou, China. ((::?) / \ 4 size (210 >: 297) Gonglu) (Please read the notes on the back before filling this page)

1T A7 B7 J6 45 Ο 9 5. Description of the invention (The present invention, as applied for a patent, is to provide a treatment method. It solves the problem of providing easy-to-apply topical sebum that can be marketed to consumers more effective than previous methods. The problem of the granule treatment method, and it can cause obvious structural improvement in a reasonable time. The present invention also solves the problem of providing a local sebum granule treatment method that can produce gradual and structural improvement when continued long-term use. The preferred embodiment promotes the obvious thickening of the skin of the body affected by sebaceous particles and the strengthening of tissues, reduces the thigh and thigh circumference, and increases the microcirculation blood flow. The present invention solves the above problems by providing a sebum particle treatment method, Methods The tissues affected by sebaceous granules destroy the water barrier properties of the skin in this area for a long time, which is enough to stimulate the renewal of the treatment and the regeneration of blood vessels to achieve enhanced effects. It is difficult to destroy the skin barrier for a long time. The method must not be so strong as to damage the sensitive dermis of the skin or cause pain or significant allergies. Effectiveness of the invention, the treatment should provide a long-lasting effect of destroying the barrier, not a temporary effect. Because the normal function of the barrier is necessary for survival, destroying the barrier will cause a natural response to quickly repair the barrier. In more detail In the weeks of extended treatment, such as 8 weeks or longer, the barrier effect must be continuously destroyed. The increase in water loss penetrating the epidermis can be used to monitor the barrier effect. TEWL is measured after 12 weeks of treatment and at least 8 hours after the last treatment Measurements found that known sebum granule treatment methods other than retinoids have little sustained effect on the barrier effect, and some seem to reduce TEWL. Retinoids, a peeling agent, and at least another exfoliating agent, in Only show TEWL at 12 weeks. This paper size is applicable to Chinese national standard ((: NS) Λ4 specification UIOX 297). (Please read the precautions on the back before filling this page.) '1Τ Printed by the Industrial Consumers Cooperatives 46 45 0 9 Α7 Β7 Printed by the Consumers ’Cooperative Standards Bureau of the Ministry of Economic Affairs, Du Printing 5. Increasing the number of invention descriptions. Despite these difficulties, the Many treatments are effective in breaking the barrier effect * and when used continuously for a long time, such as once or twice a day, can produce a significant increase in TEWL at 8 or 12 weeks. Barrier destruction methods that can be used in the present invention include low molecular weight The organic solvents acceptable for children's non-sexy waxy skin such as acetone, or skin-acceptable surfactants such as sodium dodecyl sulfate, directly physiologically and chemically break the lipid structure of the stratum corneum. This type of method is difficult to remove and remove the lipids of the barrier constituents. However, it is preferable to use a topically applied meal-preserving composition which is aesthetically attractive that can be absorbed by the skin * non-odorous formula such as cream contains chemical Active barrier rupture composition. Other suitable barrier destruction methods are known or clear to those skilled in the art. It was further discovered that by inhibiting the synthesis of dermal lipids, the repair of the barrier can be inhibited or controlled for 8 or 12 weeks. The increase in TEWL can be significantly enhanced. As Proksch et al. Teach in "Barrier Function regulates ep i derma 1 lipid and DNA synthesisw British Jouna1 of Dermatology (1993) 128, 473-482, rodent research has shown that the destruction of the barrier effect will cause the prevention of free lipid in the active layer of the epidermis. Increased synthesis of acids, sphingomyelin, and cholesterol, leading to repair of the wall. In an alternative embodiment of the present invention, inhibition of such synthesis reduces the availability of free fatty acids, sphingomyelin, and cholesterol for repairing the barrier. For example, by topical application of cerebroside for absorption. Other suitable inhibitors are known or clear to those skilled in the art. When sebum granule treatment methods remove or wash away the skin »lipids, lipid synthesis inhibitors are different from barrier destruction ^^^ 1 · ^^^^ 1 In i ^ n ^ (谙 Please read the precautions on the back before filling this page) This paper size is applicable to China National Standards (CNS> A4 Grid (210X297mm) ) 9 464509 Α7 Β7 V. Description of the invention (). When the barrier destruction is achieved by topical application of an active agent, a lipid synthesis inhibitor may be included in the formulation. Such lipid synthesis inhibits The use of the formulation prevents rapid regeneration of the water barrier and provides structural improvement in the condition of sebum granules. At the same time, it was found that for prolonged long-term sebum granule treatment for 8 weeks, the water loss through the epidermis (Yewl (which can be directly measured )) Is a very valuable indicator for monitoring the efficacy of sebum granules. The extent of TEWL increase on a continuous basis is also useful in predicting the efficacy of sebum granules treatment, because its efficacy is only after long-term use. It becomes apparent after two to six months or longer. By measuring the TEWL of various sebum treatments, I believe it has not been used to evaluate the efficacy of sebum treatments and found that known treatments only provide TEWL temporarily And a brief increase, and none of which provided a continuous increase in TEWL for weeks or months. It was found that by inducing and increasing the increase in TEWL, a favorable structural improvement in sebum status can be achieved. 0 Ministry of Economic Central Standards Printed by the Bureau ’s Consumer Cooperatives (please read the notes on the back before filling this page) In addition, by monitoring the TEWL level caused by various metallurgical treatment methods, Design a new treatment method for sebum granules that can maintain a long-term or continuous increase in TEWL during treatment periods typically up to 8 weeks, 12 weeks, or longer. Preferably, the new period is 8 weeks or longer. Therapeutic methods increase T £ WL by at least 100%. A substantially higher increase of 200% or 300% during the treatment period is advantageous. In one aspect, the invention provides a method for improving the condition of sebaceous granules, which includes the affected skin The local area was treated with local water barrier rupture treatment, and the long-term increase in penetration during the period from 8 weeks to the improvement of the desired sebaceous granules was achieved. This paper applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm). 10 A7 B7 Five Central Ministry of Economic Affairs, Central Cotton Standards Bureau, Consumer Work Co-operative Cooperative, Printing M 464509, Description of Invention (8) Skin moisture loss. The treatment is generally administered once or twice daily. Many new sebum treatments include various local mechanical treatments of the skin,

J For scrubs, roughening or extraction or solvent extraction treatments, both treatments are applied violently or aggressively to enable TEWL to be increased by 100% or more as described above and maintained for a long time. However, preferred treatments include a chemical composition that can be applied topically, preferably in the form of a softener or cream, and that maintains an increased level of TEWL at a frequency not exceeding one or two applications per day. Clearly, the urgency of the treatment method of the present invention must be controlled so that it can be accepted over a period of weeks or months without causing severe or painful allergies, redness' peeling or excessive discomfort. However, many people can tolerate the short-term appearance of these symptoms. Another aspect of the present invention provides a sebum granule composition comprising a TEWL increasing agent capable of increasing TEWL immediately or short-term, and a barrier-damaging agent which acts to maintain the increased TEWL level. Preferably, the composition also includes a skin lipid inhibitor, to prevent premature reconstruction of the water barrier and enhance the therapeutic effect of the composition on the sebum particles. In a preferred embodiment of this aspect of the invention, the TEWlJf additive is a cosmetically compatible hydroxycarboxylic acid with a reduced pH, preferably has the properties of a peeling agent, and is at least moderately soluble in water or hydrogenated alcohol Enables inclusion in a cosmetic composition. Such acids include alpha-hydroxycarboxylic acids, especially such as lactic acid and glycolic acid, and other hydroxycarboxylic acids, such as 2-hydroxycarboxylic acid, especially salicylic acid. The effectiveness of these acids seems to be related to their ability to lower the skin's intercellular fluids. The acid used and its concentration are chosen to achieve the desired increase in TEWL without causing excessive hypersensitivity. (Please read the notes on the back before filling this page) Order -11-46 45 0 9 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () The best barrier repair inhibitor is retinopathy Gadolinium or its derivatives, particularly preferred retinoic acid is betaine A palmitate. A clinical trial involving in vivo testing of human responses to various sebum granule treatment methods, fascinated by the details, shows a rather unexpected and beneficial interaction between lactic acid and vitamin A palmitate * its long-term effect on sebum granules Treatment is favorable. Preferred lipid synthesis inhibitors are cerebrosides or cerebroside-rich substances. Other optional ingredients are diuretics that stimulate blood flow and remove excess fluid, and anti-allergic agents that alleviate the side effects of T EWL increasers or cell regeneration stimulants. Suitable relative proportions of the composition formulations of the composition of the present invention sold as cosmetic or medicinal peeling agents, emulsions, or nourishing formulations for local application and the frequency of their application are described below. The preferred makeup formula is a cream suitable for consumers to massage daily, or just apply or rub >. Other such quantitative indicators that can be used to achieve the advantages of the invention are known to those skilled in the art. The experimental data under M show that the composition according to the present invention provides a new degree of efficacy in treating sebum particles, and can significantly increase the thickness of skin cells *, increase blood flow and promote angiogenesis. As reported, the efficacy of these and other products has been carefully quantified. Sebum region has poor blood flow. The clinical trials reported in the examples of the present invention show immediate improvement in blood diarrhea for 4-8 hours, compared with 8-16 weeks for long-term users, and long-term improvement of blood flow through angiogenesis, thus reducing the effects of sebum particles. Organizational defects. In addition, the thickness and density of epidermis-dermal skin * regions were increased in the subcutaneous area after 8 to 16 treatments. More importantly, the increase in tissue density shows that this is a positive effect and fog (please read the precautions on the back before writing this page) -9 This paper size applies to China National Standard (CNS) Λ4 specification (2 丨OX297 mm) 4 6 45 0 9 Consumption cooperation between employees of the Central Bureau of Standards, Ministry of Economic Affairs, Du printed A7 ____B7_ V. Description of the invention (), and the epidermis is firmer and more flexible * and the subcutaneous area has less fat and will reduce external liquid. These are due to the structural improvement of the treatment method of the present invention. The occurrence of sebaceous granules can usually be described in three or four stages. Here, in order to provide an explanation mode without limiting the scope of the present invention, the occurrence of sebum granules will be regarded as a three-stage process having the following properties: The first stage is vasodilation, relaxation, and leakage of the blood vessels in the affected area. At this stage, the impact on the surface is light, and treatments that repair vascular integrity and remove excess fluid can be very effective. Laser Doppler tests can detect abnormal blood flow and biopsies can show subsurface defects. The second stage, due to the rapid increase in fat and cell size, disrupts the metabolism of fat cells inexpensively. The fat entrapped by thunder sticks together to form fat globules. The integrity of the blood vessels is further impaired, and the affected papillae of the dermis and epidermis can also be seen. Examples of this type of shadow are thinning of the epidermis and poor distribution of dermal blood vessels. Due to the poor withdrawal cycle, the skin surface becomes rough and gray and the surface is uneven, that is, the formation of "orange peel surface S" can be seen in the opening and closing. . The third stage In the third stage, continuous rupture of the vasculature distribution and perpetual accumulation of fluid > increase in fat synthesis and decrease in fat metabolism rate were observed. Lipid cells are swallowed, stored together, and surrounded by a collagenous shell formed by abnormal peptones. These distinct nodules can be several centimeters in diameter, are visible on the surface of the skin, and can be very painful. This collagenous lipomas are redirected to the microvascular network and represent areas of reduced blood flow. Due to fluid accumulation, the presence of lipomas, and the effects of gravity, the subcutaneous lipid defense zone is very fragmented. The orange peel-like skin is clearly visible, and (please read the precautions on the back before filling this page), 1T This paper size applies to Chinese national standards (CNS > A4 size (210X297 mm), Λ -13-464509 A7 B7 Printed by the Consumer Cooperative of the Central Bureau of Probability of the Ministry of Economic Affairs 5. Description of the invention () The heterogeneity of the surface is obvious. The epidermis and dermis become thinner and less strong and poorly organized. You can see it on the skin * surface It is abnormal and unsightly and embarrassing for most people who are affected by heavy sebum particles. Several biophysical methods can be used to measure and record sebum particles, for example, by measuring blood with a laser Doppler Flow can be directly measured for firmness and elasticity through temperature recording and histological evaluation. According to the symptoms targeted by the treatment method, the effectiveness of a specific sebum particle treatment method can be measured using various techniques. Other technologies have also been developed to Improve clinical evaluation of these sebum granule treatment methods and compositions. Below is a short, but not exhaustive, list of such treatments: Thigh diameter measurements track the area of thin sebum granules The efficacy of the product. It is most effective for the treatment methods involving diet and lotus movement. This is a poor, insensitive and non-differential method. Laser Doppler measurement can detect the damage of blood vessel distribution and produce integrity of blood vessel distribution Effect. It is easy to observe the short-term vasodilation effect caused by the product. The long-term observation of the angiogenesis (angiogenesis) effect and vascular integrity caused by the better product can be formed, but it is more difficult and requires Good technical expertise. Ultrasound scanning is a very effective technique. Can detect changes in subcutaneous fat, blood vessel distribution, and epidermal and dermal integrity. Can analyze skin lesions by computer analysis Thickness. Ultrasound scanning provides an objective and accurate non-invasive method for measuring the thickness of epidermis and dermis. Thermography is a more graphical method than laser Doppler to show the lack of blood vessels. Skin firmness and elasticity measurement One of genuine leather, epidermis and subcutaneous area (please read the precautions on the back before filling this page)

, ST This paper size is applicable to China National Standard Vehicle (CNS) A4 specification (2! 0X297 mm) 14-464509 A7 B7 V. Description of the invention () Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economy General health and integrity. Sebum Grain Classification The sebum granule classification described here is a number representing the total result of the visual inspection of the tumors and flaccidity of the skin and examination of skin defects and skin lesions. Histology and histology (examination of the skin biopsy method) can show changes in measurements such as the synthesis of protoplasts and elements, and neoangiogenesis, as well as the ability to record structural changes. Group studies are usually the most accurate way to describe the extent of sebum problems and determine the actual effect of a product, but they are invasive and have other shortcomings. Photos and copying have limited effects. Consumers' impressions are usually better tools. Sebum granules are the "big" skin effect, and replication often shows too much detail. Photos are difficult to evaluate. Comparative Examples of the Invention In the preferred embodiment of the present invention, the use of the method or substance M causes the loss of the function of the skin barrier to cause the release of factors in the skin that substantially begin the skin repair process. By breaking the barrier, the skin responds as if it were injured and begins a general repair process, which increases the metabolism and renewal of the epidermis and dermis, or the formation of blood vessels. This process is currently released when the barrier is broken. Undefined, please control the skin province signal = Observations during the establishment of the following reported data show that massage, friction sea line (BUFF-PUFF (商 檫)), and peeling particles may temporarily increase after use TEWL can't hold on to this effect for minutes or hours. From these observations, it is concluded that the long-term increase in TEWL is necessary to achieve the desired structural improvement. (Please read the precautions on the back before filling this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 15 464509 Employees' cooperation cooperation of the Central Standards Bureau of the Ministry of Economic Affairs, printed A7 B7 5. Description of the invention ( ) Similarly "peeling treatment such as facial peeling (for example, 20-30% lactic acid or glycolic acid or equivalent) single use or intermittent repeated use such as once a week, although TEWL is increased for several days after treatment, but The desired skin repair and sebum particle improvement effects have not been achieved. In addition, as in the concept of the present invention, its lack of efficacy is due to the failure of the treatment method to maintain the TEWL increase rate over a long course of treatment, such as up to 8 weeks. The experimental data described below show that there is no continuous destruction of the barrier effect caused by sebaceous granule treatment methods known before M, and none of which can be applied locally and regionally to restore the severely affected areas of sebum grains to normal or Sufficiently obvious effect to approximate normal conditions. TFWL: > Tide deterrence TEWL is measured by individuals who have received various sebum granule treatment methods, including Fu Tong's treatment method and some of the new treatment methods according to the invention, according to the present invention. At the same time, the measurement of basic blood flow, the measurement of the diameter of large sleep, the comparative clinical classification of sebaceous granules, and the allergies caused. TEWL was measured with a SERVD-MED evaporator. The instrument includes a stack of moisture collection chambers that encloses a skin area on the skin. The instrument measures conductance as a function of moisture and reads TEWL when steady state is reached. Individuals were pretreated at a temperature of about 68-7ΓP and fold-to-wolf degree: the sensitivity of the instrument used for the sub-test was about ± 10%. In the clinical trials reported below, the method involves measuring TEWL in the cream area of the topical application of sebum granules. Sebum granules and other comparative local treatments are administered twice a day, while TEWL is measured in the morning. Performed shortly before application. For example, in many cases * the treatment method is about (please read the precautions on the back before filling this page) This paper size uses China National Rubbing (CNS) Α4 specifications < 2ί〇 × 297 mm} 16 A7 B7 464509 5 2. Description of the invention (at 10 am and 6 to 8 p.ro. administration 'and TEWL measurement is performed at about 9 a.m., about 1 hour before morning application and at least 8 hours after evening application) or longer. Use the method described in the previous paragraph to evaluate the effectiveness of some sebum granule treatments in improving TEWL. Basal blood flow was measured with a laser Doppler and then rated for comparison. In addition, the thigh firmness and diameter were measured by a method known in the art, and the skin thickness was measured by the ultrasonic method described above. The thickness of the skin is determined by measuring the epidermis and cortex as the first data, and also measuring the subcutaneous area as the second data in brackets. When treatment improves the structure of the skin, the epidermal-dermal layer thickens (the first data increases) and the soft, water-containing subcutaneous area decreases due to improved microcirculation except for excess fluid (negative data in parentheses). The severity of sebum granules is clinically graded on a comparative scale * as is the allergic effect. In the following clinical trials, the classification of sebum granules is determined according to the following grades: 0 No surface depressions or defects. 1 Discontinuous depressions or depressions visible on the surface of the eye. 2 Large linear sulcus (dent on the surface) visible to the eyes. 3 Multiple ditches or depressions visible and obvious on multiple eyes, uneven skin tone and color variation. 4 As a grade 3, there are obvious nodules. Allergies are based on Minolta Chroma, Minolta Camera Co,

Ltd.'s industry standard method for comparative colorimetric determination of skin color. In addition, record other subjective feelings such as irritation, burning and skin redness after application (please read the precautions on the back before filling out this page) Order ^ Standards in the Ministry of Economics. Μ} Μ X Consumer Cooperative Seal 464509 A7 B7 Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Bureau of Standards 5. Description of Invention (), and this information is included in the Clinical Allergy Index, which has a scale of 0 to 5, 0 means no identifiable or reported allergy, and 5 means severe allergy. The clinical results of the conventional methods for the treatment of sebum granules are reported in Table 1 below. The conventional art active substances in Table 1 were applied twice daily during the experiment. Treatment method 1.1 Retin Α (商 檫) was applied at a simple cream base of 0.5%. The massage method of treatment 1.2 is performed by hand * and the mechanical method is to use olive oil as a massage oil. The concentration of caffeine and theophylline in simple gum in Treatment 1.3 was 2% and 0.2%, respectively. Therapeutic method using heat and scutellaria baicalensis 1.4 uses a product from La Prairie with the trade name "Cellular Body Contouring Gel", which can increase the temperature of the skin surface through chemical reactions. The peeling method of treatment method 1.5 is a mechanical peeling of 5% polyethylene beads suspended in carbopol gel and applied and washed off twice a day. The vascular active medicinal plant of treatment method 1.6 is a product from Orlande under the trade name wRhyt + hne Du Co.rps. (Please read the precautions on the back before continuing on this page) The paper size of this paper applies Chinese national standards { CNS) A4 specification (2 丨 OX297 mm) 46 45 0 9 Α? Β7 V. Description of the invention () Printed in Table 1 by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, the evaluation of the traditional sebum granule treatment method. Blood flow TEWL Strong thigh skin thickness thickness sebum allergy g / m2 / hr diameter grade grade 1.1) RETIN A " 0.5S bottom line 1 2.17 XXX 4 1 8 weeks XXXXX 4 0 tk 12 weeks 1.27 2.37 32¾ SX 4% (ns) 3 2.5 1.2 ) Massage bottom line 1 2.41 XXX 4 1 8 weeks XXXXX 4 1 12 weeks 0.97 1.97 61 -21 ns (ns) 4 1.25 1.3) Caffeine / Theophylline bottom line 1 2.33 XXX 4 1 8 weeks XXXXX 4 1 12 weeks 1.08 2.47- 3% -3¾ 2¾ (ns) 3.75 1.25 1.4) Hot / yellow line 1 2.61 XXX 4.25 1 8 weeks XXXXX 4.25 1.25 12 weeks 1.03 2.23 4% -57, ns (-2X) 4 2 1.5) Peeling effect line 1 2.41 XXX 4.25 1 8 weeks XXXXX 4 1.5 12 weeks 1.07 2.17 m -3% ns (-3¾ 4 2.25 1.6) vascular active medicinal plant bottom line 1 2.23 XXX 4.25 1 8 weeks XXXXX 3.75 1.25 12 weeks 1.01 2.41 η U ns (-3% ) 3.75 1.5 * Johnson & Johnson's retinoic acid commercial habitat ns = not obvious (please read the precautions on the back before writing this page) The size of the paper is applicable to China National Standard (CNS) A4 (210 X 297) (Mm) 19 Printed by the Consumer Cooperative of the Central Sample Vehicle Bureau of the Ministry of Economic Affairs 4 6 4 5 0 9 Α7 Β7 V. Description of the invention () The first five columns of the results are used for statistical significance analysis, and only the treatment methods 1.1 to 12 weeks The results of blood donation, firmness and thigh diameter are remarkable. (The clinical analysis of sebaceous granules in severe and allergic columns in columns 6 and 7 is subjective and not statistically analyzed.) Regarding this data, only retinoic acid of the treatment method 1.1 showed significant basal blood roll. The improvement of the treatment method 1.3 and the peeling effect of the treatment method 1.5 and the treatment method 1.5 show only a small but insignificant increase in blood flow. TEWL on Table 1 and the degree of comparison and the degree of the bottom line in 2 weeks * It can be seen that even at 12 encounters, the sebum granule treatment method of the known technique rarely increases significantly. Treatment with retinoic acid 1.1 showed the best increase but only 10%. The treatment method of the present invention can achieve an increase in blood flow of more than 40%. The peeling effect of treatment method 1.5 only slightly improved thigh firmness and diameter, while treatment method 1.1 significantly improved retinoic acid. The present invention can achieve substantially more significant improvements. The sebum granule treatment method of the conventional technique S shown in Table 1 shows only a slight or insignificant improvement in the thickness of the skin. As reported in the last two paragraphs of Table 1, the flavulinic acid of treatment method 1.1 shows the severity of fur wax granules, such as the general reduction of clinical grade *, but its allergic response has increased significantly. These data show that known sebum granule treatment methods provide only withdrawal effects, with the best result being retinoic acid and the second best being peeling. In the general conditions of basic blood flow, funding, thigh diameter, and skin size, this paper size applies to China National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling out this page) i -

• IT -20-464509 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 i. Invention description () can achieve improvement * but cause significant allergies. None of the treatment methods used in the conventional techniques has shown a significant increase in TEWL or an improvement in the thickness of the skin, which is an indicator of the basic structure of the skin cream. This clearly shows the shortcomings of the conventional technique 15. Although the present invention is not limited to the theory to be determined, there does not appear to be a conventional treatment method that provides a significant breakthrough in the function of the skin barrier of the skin barrier to stimulate apparent skin repair. Method for chopping sebum granules As described above, the present invention provides a local treatment method for sebum granules, which reduces the function of the water barrier of the skin grafts. * It is better to hold and increase TEWL 200 to 300% or more for a long period of at least 8 weeks. During and preferably over 26 weeks or until a satisfactory improvement in sebum status is achieved, such as 10 to 20 weeks. The beneficial increase in TEWL can be achieved by the treatment of appropriate chemical composition or mechanical rupture or solvent extraction, as long as the treatment can be broken quickly enough. The important part of the present invention is that while increasing TEWL, it also maintains a low, tolerable allergic reaction. Corrosive chemicals used to break barriers, solvents used to extract lipids, and surfactants can be very specific. By nature. In a particularly preferred embodiment of the present invention, it has been found that a relatively high concentration of unbuffered lactam * is one of ex-hydroxy acids, and a combination of thiamine or sodium salt can increase TEWL additively. cr_hydroxy acid breaks the water barrier of the skin and acts as a TEWL increasing agent. Vitamin A palmitate, a retinoid, appears to be able to inhibit the recovery of the barrier function and delay the recovery of EWL which is increased by ct-hydroxy treatment. These TEWL-stimulating properties can be attributed to the crypts of retinin-derived * cell differentiation. The interaction between vitamin A palmitate and lactic acid is that this paper size applies the Chinese National Standard (CNS) A4 specification (210 × 297 mm) I --- I --- ^-^-(Please read the back (Notes continued on this page)

1T 21 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 46 45 0 9 A7 B7 V. Description of the invention () Quite unexpected. The preferred embodiment of the present invention, when topically applied to dermatologically, is believed to cause long-term and severe peeling of the skin cells, resulting in heavy loss of dermal ligament cells, and more importantly disrupting normal barrier function and increasing TEWL to It is preferably up to 200 to 300%. Although physical methods can be used to achieve these effects, the present invention has found that between 5-10% unbuffered lactic acid and 0.1% -3.05¾ vitamin A palmitic acid can produce this result and cause only moderate allergies. It was found that a combination of 6% lactic acid and 0.5% betaine A palmitate was particularly effective. Long-term high TEWL levels are thought to trigger the release of key skin growth factors such as interstitial cells and transforming growth factors, which in turn stimulates dermal-epidermal growth and angiogenesis effects. This type of treatment may be too harsh to be used on the skin, but it is more resistant to the skin in the thighs, arms and chest areas that are susceptible to sebum. The treatment with the above-mentioned button compounds thickens and improves the dermis and epidermis containing shout sebum particles, and the angiogenesis effect improves long-term blood flow conditions. In order to achieve further and sustained increase in TEWL, it was found that the addition of a specific cerebroside, type I or type E, can exert an additive effect with the above composition. I and E can be understood to mean specific molecular structures by referring to the corresponding ceramide, see, eg, Rieger, Table 2, page 88. In the metabolism of Pirup, brain ceramide is made by sphingosine, and cerebroside is the glycation product of ceramide. Cerebral amines and cerebrosides account for only a small percentage of the lipids of the skin, and are present in the outer layer of the skin, while sphingosine, the precursors of which are mainly found in the base layer of the skin. Sphingosine is also stored in exfoliated stratum corneum cells in a significant amount. Because ceramide is fermented during the peeling process, the paper size applies the Chinese National Standard (CNS) Ad Specification (210 × 297 mm) (Please read first (Notes on the back are reproduced on this page), ιτ 22 464509 A7

Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs. The treatment method for breaking the barrier of the present invention releases a message to the lower layer M of the skin corpuscle that increases the synthesis of lipids such as ceretonamine and repairs the barrier. The non-limiting hypothesis of the present invention is that the administration of cerebroside I or I would interfere with this synthesis and crudely stop the self-repair of the barrier. General inhibitors of lipid synthesis other than cerebroside I or Π * or other end products of dermal lipid synthesis, can also be an effective supplement for the above-mentioned treatment methods to maintain increased TEWL and promote long-term skin * repair . An article published by Dr. Sergio Curri at the Cosmetic &amp; Toiletry Convention in Barcelona, Spain, in March 1994 states that inhibition of protein kinase C, such as sphingosine, can be a useful treatment for sebum particles. The suggestion means that cerebroside is not helpful in treating sebum particles. In experiments not reported here, it has been found that for the purposes of the present invention, phospholipids, ceramides, and sphingosine have little effect as barrier repair inhibitors, and further found that cerebroside itself is controlling TEWL or treating sebum Grain doesn't help. A further advantageous and important function of the sebum granule treatment method is to reduce or eliminate the accumulation of the unpleasantly stimulating subcutaneous fat mass which is a sebum granule. According to the purpose of the present invention, by stimulating the metabolism of lipids * slopingly * by increasing the skin * enzyme ATPase and protein kinase C, the skin * 's accumulated fat can be slowly and naturally broken down. It was unexpectedly found that by incorporating cerebroside into a topically applied cosmetic composition, the metabolism of lipids can be suppressed. The present invention is not limited to a specific theory, but is limited only by the scope of the attached patent application. It seems that cerebroside is in the stratum corneum (please read the precautions on the back before filling this page),? Τ This paper size applies China National Standard (CNS) A4 specification (2 丨 0X297 mm) 6 4 45 0 9 A7 B7 V. Description of the invention (Employees of the Central Bureau of Standards, Ministry of Economic Affairs, Consumer Consumption Cooperation, Du Printing Barrier Regeneration plays a specific role. When the Barrier When destroyed, specific signals are released, triggering the activation of the epidermal and dermal metabolism. Some of these signals activate the synthesis of new epidermal lipids to repair the barrier and restore TEWL to normal. This repair effect will be turned off Corruption signals signals to the epidermal and dermal metabolism (and activates the synthesis of new blood vessels under the skin). The selected cerebroside (but not ceramide or sphingosine) interferes with the repair of the barrier to the epidermal and dermal metabolism. Activation can be maintained for a long period of time, resulting in changes that can improve the condition of sebum granules. Dry sowing of the barrier repair caused by the selected cerebroside does not cause skin captives The negative effect. Instead, it seems to be interfering with the production of epidermal lipids, which can metabolize the epidermal and dermal metabolism and can sustain periods of time and months. These concepts are confirmed by the results of clinical trials reported below. These The conclusions and results about the role of cerebroside's barrier repair inhibitors are unexpected, because traditional teachings point out that cerebroside should repair the cleft dysfunction. It is concluded that the effect of cerebroside is very uncertain and is in the stratum corneum, However, this theory is only provided to explain the mechanism of the present invention according to the understanding of the present invention. Progressive research may show other mechanisms. Cerebroside may also directly affect fatty wax in the subcutaneous region through the action of protein 擞 enzyme C. When the topical treatment method is incorporated, the cerebroside composition has a long-term effect, such as more than 10 to 20 encounters, and improves the quality of skin concerns and the condition of sebum granules. The experiments described below show that , TEWL increasing agent, especially lactic acid, --------:-V-- (please read the precautions on the back before filling this page) Furniture Standard (CNS) A4 (2IOX297 mm) 24 46 45 0 9 Α7 Β7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () and retinoids, especially vitamin A palmitate and The inhibitor of skin #repair wall repair * especially cerebroside, preferably type I or type I cerebroside, the combination can produce continuous and long-term increase of TEWL and the destruction of the barrier function, leading to the above-mentioned favorable skin repair And the effect of improving sebum granules. TRtf 丨. Pujia_: Unloading a certain pound of acid. Preferably, TEWL increasing agent is soluble in water or some polar hydrogenated alcohols to provide an effective solution that incorporates the basic ingredients of cosmetics. In addition to In addition to lactic acid, many other α-hydroxy acids can be used. In the present invention, lactic acid is a particularly good TEWL increasing agent, which has good efficacy and is a substance naturally present in the skin, intercellular fluid, and blood. In addition to lactic acid, glycolic acid, salicylic acid and mixtures of these acids are preferred. In order to have the desired properties of lowering the pH and increasing TEWL, as well as the compatibility of cosmetics and the solubility of moderate water or hydrogenated alcohols, the preferred hydroxybenzoic acid has less than about 250, and preferably less than about 175 * Molecular weight. Many useful hydroxycarboxylic acids are described in International Patent Application WO / 94 / O6640. Some other ex-hydroxycarboxylic acids are described in U.S. Patent Nos. 4,363,815 and 5,091,171 to Yu and Van Scott. The acids and acid equivalents in these documents, and their published parts, are incorporated herein by reference only * and can be used in the present invention when the above conditions are met. Preferred 1 The hydroxy acid used in the composition of the invention is preferably a linear or branched aliphatic acid, and the aliphatic skeleton does not contain more than 3 dip substituents, which are non-basic and are selected from hydroxy , Aldehyde, ketone, carboxyl, chlorine and nitro. Although the acidity and the solubility of water or hydrogenated alcohol are the desired characteristics of the α-hydroxy acid of the present invention *, any extreme of these properties, as shown by the inorganic acid I --------- V-- (please first Read the notes on the back and fill in this page), 1T This paper size applies the Chinese national standard (CNS &gt; A4 size (210X 297 mm)) Printed by A7 B7 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs It is unfavorable because it will not only cause allergies, but also cause serious clinical conditions such as burns, injuries, and subcutaneous penetration. Low molecular weight substances sometimes also show these unfavorable properties, which may show no longevity and unpredictability. , And special behaviors that are generally harmful. Other such hydroxy wax fatty acids useful in the present invention are preferably monocarboxylic acids selected from 2-hydroxy-η-butyric acid, 2-hydroxy-isobutyric acid, 2- Hydroxy-η-valeric acid, 2-hydroxy-isovaleric acid * 2-hydroxy-η-hexanoic acid, 2-hydroxy-isohexanoic acid. Its bis- or polyhydrogen analogs can also be used, for example, its 2, ×- Dihydroxy analogs, where X is an integer from 3 to 6, depending on which monohydroxy acid is suitable The position of the phosphorus atom of the second hydroxy substituent of the atom is not the one or two carbon atoms. Preferably, this type of dihydroxy acid balances the additional electronegativity caused by the more hydrophobic portion of the second hydroxy group as described above. Suitable dihydroxy acids include aaleic acid, ((:} 1. (: 0〇 [1) 8 and azelaic acid, HOOC.iClUh.COOH. Mubi function 冏 multiple grapefruit shovel according to the present invention, a preferred barrier Functional inhibitors are retinoids, such as tretinoin, or retinoic acid. However, many retinoids or retinoic acid are unstable and unsuitable for sale in topical therapeutic compositions for cosmetics. Vitamin A Brown 櫊Acid salts are particularly stable retinoids and are therefore preferred for use in the present invention. Other stable retinoids suitable for formulations such as the compositions of the present invention include retinyl acetate and retinol. Others have a link to Stable retinyl fatty acid chains that provide oil stability and good solubility in the topically applied carriers described herein may also be used in the composition of the present invention. In the method of the present invention, the shelf life may not be Important. Therefore, if applied topically The formula is made only when needed. The paper size is applicable to China National Standard (CNS) Α4 specification (2 丨 〇 × 297 公 嫠) 26 --------. I— V —— <Please read the precautions on the back before reading (Fill in this page)

1T 6 4 45 0 9 A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (If it is manufactured and will not be stored for a long time, the stability of the selected retinoid will be less significant 箸Instead, less stable retinoids can be used. Many active retinoids can be used in the present invention, as listed in US Patent No. 5,051,499, which is incorporated herein by reference. Other such retinoids include Vitamin A aldehyde, Vitamin A acid, Vitamin A ester, Retinic acid, etretinate, acid retinin, 13-cis and 13-trans-retinoic acid esters And retinoids and retinoids. Inhibition of wall repair and inhibition as described above, it was found that cerebroside has an advantageous function as an inhibitor of barrier repair in the present invention. This function is considered to be incorporated into the stratum corneum through inhibition and thus It is formed by the synthesis of lipids that provide normal water barrier function. In accordance with this concept, other substances are also considered to have the desired role in inhibiting the repair of the barrier wall. The cerebral glycosides used in the present invention can be obtained in the form of a number of commercial products. Sometimes they are With sugar Supply via transsphingomyelin (GSL), the term refers to any lipid and sugar linkage with a sphingomyelin. As supplied, cerebroside is the main component of GSL * which is sometimes a crude biological isolate from a plant or animal. A relatively pure mixture of Type I and Type I bovine brain cerebroside can be obtained from Sigiw Chemical Co., Catalog No. C 4905. Relative Ratio of Compositions The limitation of the strength of the sebum granule therapeutic composition of the present invention is its The degree of allergies. The skin captives in the areas affected by sebum are generally less sensitive than the facial skin #, on which there have been "wrinkle-resistant milk boxes" or "this paper standard applies to China Standard (CNS) Α4 specification (210 × 297 mm) (Please read the precautions on the back before filling out this page), 1T 27 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 45 Ο 9 A7 --------- -V. Description of the invention ("Anti-aging cream" formula tests some possible constituents in the composition of the present invention. Therefore, because of the lower tissue sensitivity of the areas affected by sebum grains, new skin waxes The preferred formulation of the therapeutic composition may be Ratio, or allowable range of active ingredient ratios higher than those of creams for facial dermatology. Depending on its strength and nature, TEWL increasing agents, preferably alpha-hydroxycarboxylic acids, are used topically A useful proportion of the therapeutic composition is from 1 to 15% by weight of the composition, and a preferred intermediate range is from 5 to 10%, especially lactic acid or glycolic acid. When retinol is used as a cell regeneration tincture A useful ratio is from about 0.005 to about 6.0% by weight * preferably 1.0 to 4.0% by weight. Although ratios ranging from 0.1 to 1.0 are considered to be active, they are less effective. When cerebroside or brain When used as an inhibitor of the barrier repair of the present invention, a useful range of the inhibitor of the barrier repair is from about 0.01 to about 5%, preferably from about 0.05 to about 1%, particularly preferably from about 0. 1 to about 0.5%. Unless otherwise stated, or apparent from the content, the proportions used herein are weight proportions based on the total weight of the composition and refer to the proportions of the active ingredients or their equivalents. The nii value of hemorrhoid molybdenum products depends on the acidity of the TEWL increasing agent. The preferred pH value is somewhat acidic, and in fact, moderate but tolerable acidity is considered to promote the breakage of the barrier. Therefore, the preferred pH value is between about 3.0 to 6.2, and M 4.5 to 5.0 is more preferred. The composition of this paper is based on the Chinese National Standard (CNS) A4 specification (2IO × 297 mm) (please read the precautions on the back before filling this page), 1T 28 V. Description of invention () A7 B7 Economy Printed by the Consumer Standards Cooperative of the Ministry of Standards of the People's Republic of China ¾ The non-essential but important selectivity of the present invention is to include a component that can improve the appearance of sebum granules. This can be achieved by immediately increasing blood flow and removing excess fluid. Known diuretics &gt; such as caffeine, tea age, methyl salicylate and other similar substances are effective. The preferred substance is PRONALEN C (commercial, Centerchem, Inc.), a natural biological extract that enhances the initial acceptance of the product. In general, useful and selective additional ingredients incorporated in the sebum granule therapeutic composition according to the present invention can be incorporated alone or together as diuretics, anti-allergic agents and antioxidants, preferably K is known locally Effective concentrations in the applied cosmetics are, for example, from about 0.5 to 7.0%, and more preferably from about 1 to 3%. Diuretics promote lymphatic rejection and lipid metabolism, and cause an immediate short-term improvement in sebaceous granule status that is apparent to consumers. Suitable diuretics are vasodilators such as caffeine, baicalin and the like. Anti-allergic and anti-oxidants can be used to increase tolerance to a continuously increasing TEWL. Suitable anti-allergic agents are cola wood oil extract, green tea, asparagus, etc. * and suitable antioxidants are BHT, NDGA, vitamin E and C, and propyl gallate. The inclusion of suitable optional ingredients provides a complete and balanced treatment of sebum granules that produces rapid and significant improvements in the condition and long-term structural improvements, while also controlling allergic reactions. The application rate of the sebum granule therapeutic composition of the invention described herein with noodle sauce and honey is generally between about 0.01 to 0.5 mg of active acid component per square centimeter of skin, and (Please read the Note: Please fill in this page again.) The size of the paper used for this edition is based on Chinese standards (CNS &gt; A4 size (210X297 mm) 29 A 7 B7 Printed by the staff of the Central Bureau of Standards of the Ministry of Economic Affairs. The acid is a low molecular weight hydrophilic acid, such as C (-hydroxycarboxamidine, preferably in the range from 0.05 to 0.2 mg / cm2. Cosmetic creams are generally applied at about 2-3 mg / cm2. Active ingredients The ratio is from about 0.15 to about 30% by weight, which gives a possible application rate of the sexual component from about 0.003 mg / cma to 0.9 mg / cma. The preferred range is from about 0.01 to 0.5 ffig / cms, and M The range from 0.05 to 0.2 ng / craa per unit of skin is better. Using a preferred ratio of a total of about 7% active ingredients can give a preferred application rate of about 0.15 to 0.2 mg / cm8. This dose is preferably 2 per day Application to the area of Pilou that requires treatment. Three or four more daily applications will only waste the product and Provides better efficacy, and less application once a day will cause a decrease in efficacy. After washing, bathing and swimming, you can increase the application, up to about six times a day. Another method of breaking the deer wall besides Kcc-hydroxyl In addition to the combination of acids and retinoids that damage the water barrier, TEWL can also be increased by exfoliation of the stratum corneum, solvent extraction, etc. Acetone has also been found to be held for a long time, such as two beta months * daily or every other day acetone rinse It can break the water barrier of the skin. Biophysical measurements indicate that the rinsing method should achieve the above-mentioned long-term skin cream repair effect. Acetone can remove it in the formation of lipids and dry the barrier to repair. However, __ Natural, flammable, and flammable, and not recommended for use. For example, the data in Table 2 confirms that the broad scope of the concept of the present invention is not limited to the application of the cosmetic composition M to break water barriers and increase TEWL. And other physical and physio-chemotherapy methods. 嘐 Adhesive peeling with adhesive-coated Sailu tape adhesive peeling _ 5 to 10 times (Please read the precautions on the back before filling this page)

、 1T This paper size is applicable to China National Standards (CNS) A4 specifications (2 丨 OX297 mm) A 7 B7 Printed by the Ministry of Economic Affairs of the Ministry of Economic Affairs of the People's Republic of China on the consumption cooperation of the staff 5. The invention description () is also another effective The method of destroying the barrier, which increases TEWL by 2 to 10 times, depends on the individual's specific response. Over the course of 8 weeks, this treatment resulted in a positive biological effect consistent with useful sebum treatment. The positive results of this treatment further confirm the broad technical scope of the invention. However, as a commercial method, tape sticking has some disadvantages, including, but not limited to, the response of tape sticking varies widely depending on the carcass, and it is necessary to use expensive laboratory equipment to monitor the function of the barrier. Surfactant exfoliation It has also been found that the use of strong aqueous surfactants daily can damage the barriers for a long time. It is sufficient to use a surfactant such as 10% sodium dodecyl sulfate twice a day. When used alone, SLS is allergic when used for more than 8 weeks. The addition of sphingosine at 0.1% can effectively control and reduce the long-range allergic reaction, so that the treatment method is considered as gentle to sufficient as the practical embodiment of the present invention. It may also include antioxidants and immediate-acting anti-allergic agents, such as kola extract * cerebroside cannot be incorporated into compositions containing sphingosine. If needed * Some of these methods that are effective in increasing TEWL or non-cream treatments can be used with topically administered retinoids and, optionally, a cerebroside cranial box to extend TEWL increase and Peel® repair process. Hop Drops: &gt; Carriers Any cosmetically compatible carrier that is customarily used to deliver Stimulated Skin® Regenerated Acid to the skin * can be used in the present invention. Suitable carriers can be aqueous, or hydrogenated alcohols, or suspended oils or other hydrophobic substances. M provides common formulations as creams, lotions, tonics, and the like. The cream is used as the Bureau of the Invention (please read the notes on the back before filling in this page). The paper size of the book is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 31 6 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Preparation 4 5 0 9 A7 B7 V. Invention description (1) The best of the treatment. If necessary, the carrier can only be water, although a small amount of alcohol or other organic solvents may be required to dissolve or decompose. Young children's hydrophobic retinoids and cerebrosides. If required * The active ingredient can be formulated in a cosmetically acceptable hydrogenated alcohol carrier with about 40 to 75% by weight of water, preferably 55 to 65 or About 60%, and from about 25 to 55% by weight, preferably from about 25 to 35 or about 30% of fatty alcohols. Although some lower aliphatic alcohols, both mono- and polyvalent, can be used * ethanol and propylene Alcohol is the best choice. The inclusion of many additives and supplements in this type of carrier is well known in the art, for example. Up to 5% glycerol, preferably 1 to 2% can be used as a humectant. Drying effect and enhance the feeling of nourishment. Materials and pigments are examples of other additives. Other suitable carriers include hydrophobic suspensions from about 5 to about 60% by weight of a hydrophobic liquid suspended in an aqueous matrix, and water. If required * available from 0.1 to 10% by weight % Alkaline base * such as aqueous sodium hydroxide, arginine or triethanolamine (TEA) to adjust the pH to an acceptable range. The pH of the composition renewed by the irritating skin cream of the present invention Efficacy has a significant effect> The presence of a suitable buffer is advantageous. Any such buffer and slow balance system, together with the aging matrix, should act to provide an acidic pH value in the above range, and It is preferred to maintain the pH at 4,5 or lower. The amount of buffering agent will depend on its strength, but generally from about 0.1 to 10% by weight, preferably about 1 or 2%. Some suitable buffering agents are TEiIS (trimethyl alcohol aminomethane) buffering agent and phosphate buffering agent. According to the present invention, a topical structured sebum granule treatment method milk -------- 1-^-(please first Read the notes on the reverse side and fill out this page) • 1T This paper size is applicable to China Standard (CNS) A4 (210 X 297 mm). Λ -32-4 6 45 0 9 A7 B7 V. Description of the invention (Frost-based formula will be described below. Example # Three Ingredients; &gt; Peel B purpose granules treatment method The following ingredients are mixed according to the following instructions ("Cone η concentration and" stage "are different stages of the 橒 component added during the mixing process): Central Ministry of Economic Affairs Cetylaryl (and) cetareth-20 GMS-PEG 100 stearate PEG-100 stearate oleic silicide thirty carbon pentadecanoate triglyceride propylparaben vitamin A palmitate water glycerol butene glycol carboffier 941 methyl paraben triethanolamine lactocerebroside 1 &amp; 2 prona1en AC (centerchem) concentration 2.0 5 6 4 0. 1 1.5 45 5 6 0, 2 0.25 3. 1 8 0.15 5 Stage 1 1 1 1 1 1 1 1 2 2 3 4 (Please read the notes on the back before filling out this page) This paper size is applicable to China National Standard (CNS) Α4 size (210 × 297 mm) 33 6 4 45 0 9 A7 B7 V. Description of the invention () Spice QS 7 Water QS To 100¾-Those skilled in the art are familiar with formulating these ingredients into smooth creams for topical application. At 80Ϊ: slowly add oil layer (1) to stage (2) while mixing. When the resulting emulsion opens, the stage (3) is added and the cream becomes thick. Add the next stage (4) and the stage (5-7) when the milk tank is cooled to 55 ° C. Then cool to room temperature while mixing. In this example, vitamin A palmitate, lactic acid and cerebrosides I and I are obviously active ingredients according to the present invention, while the remaining ingredients constitute a cream carrier. The clinical results of the new sebum granule treatment method are reported in Table 2 below. The treatment methods 2.1 to 2.4M are described in the breast carrier of the above example, and the active components and ratios are reported in the table. The treatment methods 2.1 to 2.3 and 2.5 may be new, but for comparison purposes, and are not the preferred embodiment of the present invention. 0 I --- II --- ^ ---- Order II (Please read the note on the back first) Please fill in this page again) The paper size printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs applies to China National Standard (CNS) A4 (210X297 mm) 34 9 〇 5 4 6

A V. Description of the invention () Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, Form 2. The sebum granule treatment method according to the present invention, blood flow TEWI TEWL, firmness, thigh skin thickness, sebum granules, allergy g / m2 / hr, increase S Diameter 2.1) 5¾ lactic acid bottom line 1 2.0? XXX 4.25 1 8 weeks X 2.33 13 XXX 4 1.5 12 weeks 1.11 2.47 19 27 ¾ -3¾ 7% (ns) 3.75 1.5 2.2) lactic acid bottom line 1 2.11 XXX 4.25 1 8 weeks X 2.69 27 XXX 3.5 1.5 12 weeks 1.07 2.83 34 30》-Π lOUns) 3 2 2.3) 10UA / UVAP bottom line 1 2.03 XXX 4.25 1 8 weeks X 3.47 71 XXX 3.5 2 12 weeks 1.12 3.67 81 29¾ -5% 8¾ (-4! S ) 2,75 2.5 2.4) 10UA / 1XVAP /0.5^„GSL bottom line 1 1.91 XXX 4.25 1 8 weeks X 3.87 102 XXX 2.75 2 12 weeks 1.43 6,88 260 43% -11% 10 ¾ (-8 ¾) 2 2.5 2.5) 2x BL! FF PUFF treatment bottom line 1 2.14 XXX 4.25 1 tier X 2.39 8 XXX 4 1.5 12 weeks 1.07 2.31 8 6% η ns (ns) 3.75 2 2.6) 5-10x exfoliation bottom line 1 2,14 XXX 4.25 1 8 weeks X 5.37 151 11% X 6% (ns) 3.75 2.5 12 weeks 1.17 6.07 184 m -8¾ lane (-5¾) 3 3 2.7) Propane dip (once every two days) Bottom line 1 2.17 XXX 4 1 8 weeks 1.12 6.92 219 η -3¾ 65: (3υ 3 2.75 12 weeks XXXXXXXM = bottom line LA = lactic acid VAP = vitamin A palmitate GSL = glycosphingomyelin lipid ns = not obvious (please read the precautions on the back before filling this page ) This paper size applies Chinese National Standard #CNS (A4) (210X297 mm) 35 464509 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 Β7 V. Description of the invention () Refer to Table 2 * Treatment method using lactic acid 2 1 and 2.2 have a large increase in TEWL, but even the 10% lactic acid composition for the strong peeling effect of treatment method 2.2 is only about 33%. A higher degree M is required to obtain the effects of the present invention. Treatment with vitamin A palmitate added to lactic acid 2.3 showed that TEWL increased by about 71% at 8 weeks and about 81% at 12 weeks. Although these TEWL increases are more pronounced than those obtained with known treatments, the invention of the treatment of barrier ruptures increased from 2.4, 2.6, and 2.7 to higher TEWL, and from more than 100% to as high as 260%. Although the level of allergy is slightly higher, it is still tolerable. As reported in column 1, the basal blood volume * showed a moderate response to all treatments, except for treatment 1.1 (Table 1), which showed a 27% increase at 12 weeks using retinoic acid, and more significant Treatment method 2.4, which is a preferred topical absorption treatment method according to the present invention, shows a basal blood roll of about 43% higher at 12 weeks. Regarding the general status of sebum granules classified as the penultimate tangerine on the right hand side, treatments 1.2 to 1.6 reported significant improvements, while treatments 2.1 and 2.5 were not obvious or very easily withdrawn. Treatment 1.1 uses retinoic acid to improve slightly at 12 weeks, which shows a reduction of one grade point, while treatment methods 2.2, 2.3, 2.4, and 2.6 all show improvements greater than one grade of stickiness, and the best embodiment shows Improved by more than 2 値 grade points. The treatment method of dip immersion 2.7 shows an improvement of the 1 値 grading point Λ confirms the concept of the present invention. In order to ensure safety, Xianqin's classification of allergic reactions in the bed. Treatment of hypersensitivity is not acceptable. It is unfavorable to approach the classification of allergic reactions in the U.S., such as the treatment method of immersion of dimethanil | Therapeutic method 2.7, does not make this paper size applicable to the Chinese National Standard (CNS) Α4 specification {210 X 2 mm) ( Please read the precautions on the back before filling out this page) -5 36 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention () Someone unexpectedly showed a significant degree of allergy at 2.75, The preferred treatment method for the hypoallergenic spring example 2.4 indicates that the allergy grade is only 2. Lactic acid (treatment methods 2.1 and 2.2) significantly improved thigh firmness (approximately 30%) * and when retinoids (treatment method 2.3) were included, no further improvement was seen. According to the present invention, the addition of cerebroside-containing glycosphingomyelin lipids (therapeutic method 2.4) significantly improved to 43%, showing a significant structural improvement of the underlying tissue. Exfoliation (Treatment Method 2.6) showed a slight improvement, while "BUFF-PUFF" and acetone immersion (Treatment Methods 2.5 and 2.7) showed insignificant improvement in firmness. The better treatment 2.4 significantly reduced the diameter of the thighs, and the dip immersion (treatment 2.6) improved less, while the other treatments were not obvious or only slightly improved. When the treatment methods 2.1-2.4 and 2.6 are displayed in the epidermal-dermal thickness, the first data, some improvements, only the invented treatment methods 2.3, 2.4 and 2.6 show a reduction in the thickness of the subcutaneous area, the data in parentheses. In both cases, the preferred treatment 2.4 shows the best results in practice. In summary, the data reported in Table 2 show that the invented treatments 2.3, 2.4, 2.6, and 2 · 7 provide larger increases in TEWL than the comparative treatments, and that the increase is accompanied by a comparison of blood flow and skin loss that were not achieved with the comparative treatments. Improvements made by the prisoner. The better inventive composition of treatment method 2.4 showed significantly better results, with a significant increase in TEWL and a significant improvement in blood flow and a significant improvement in the structure and removal of skin and deeper tissues. In order to evaluate the improvement of the circulation, a detailed blood flow study was performed using the above-mentioned ultrasonic analysis, and the results are shown in Tables 3 to 6 below. (Please read the precautions on the back before filling this page) The size of the paper is applicable to the Chinese national standard (CNS &gt; Α4 size (210 × 297 mm) 37-V. Description of the invention () A7 B7 Table 3 uses laser doppler The effect of withdrawal cycle test composition of the metastatic assay on the normal pelvic blood flow rate is summarized in the 5 carcass, and 10 blood flow measurements were performed before each body. The blood flow measurement test group was less than 1 between 1 and 3 Before 3 and 5 are between 5 and 7 &gt; 7 3 11 22 10 4 8 weeks later 1 9 20 14 6 16 after encountering 0 5 21 17 7 stimulants 0 0 0 3 47 (Please read the notes on the back first (Fill in this page again.) The blood flow measurement results printed and displayed on Table 3 by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs are the relative digital display. 缌 A total of 50 points of measurement * As shown in the table, the last of Table 3 A row of control stimulants with a blood flow of more than 7 accounted for 47 of 50%. From the table, when the period from the initial readings progressed to 8 and 16 weeks after treatment with the test sebum granule composition, The readings for each group move to the right. This shows that the application of the test composition caused The number of volume measurements increased significantly. While the number of blood flow readings in the intermediate paste (with values between 3 and 5) remained roughly stable, those below 3 (measurements in columns 1 and 2) to The initial 4 decreased to 10 in week 8 and 5 after 16 weeks. With reference to the two columns on the right hand side, it can be seen that the number of measurements exceeding 5 before treatment was only 14 but increased to 20 at 8 weeks. After 16 weeks it increased to 24. In general, this paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 38 4 6 4 5 9 Α7 Β7 V. Description of the invention () This number varies with time and blood flow The improvement is shifted to the right. Therefore, Table 3 shows that the applied sebum granule therapeutic composition is effective to provide significant blood flow stimulation at 8 weeks * and continuous administration of the therapeutic composition provides a continuous increase in blood flow, Shows a further improvement at 16 weeks. As seen * Table 3 measurements were taken on the forearm of an individual with normal, wax-free skin *. This data clearly shows the composition of this topical application The nature of the material stimulates blood flow and eliminates self-receiving sebum particles Complications due to the abnormal structure of the shadow tissue. Table 4: Laser Doppler measures the blood flow rate of circulation problems in the microcirculation thigh area (please read the precautions on the back before filling this page), and order the Ministry of Economic Affairs The results printed by the Central Bureau of Standards Consumer Cooperatives in 10 値 individuals are summarized: all show sebum levels 2/3 &gt; 30 measurement test groups in each carcass less than 1 between 1 and 3 between 3 and 5 Before 5 and 7 &gt; 7 68 133 42 43 14 After 8 weeks 45 123 67 52 13 After 16 weeks 17 67 128 71 17 Control group-not involved 6 51 128 110 5 Reference data: The average age of the control group was 23.6 years. Use known tinctures, such as Peruvian resin, to increase blood flow to 10-12 in this method. Table 4 shows the weight of sebum granules at 10 値, which meet the criteria of the second or third stage of the sebum granules of the upper palate, and a total of 3ϋ0 thigh regions. This paper size applies the Chinese National Standard (CNS) Α4 specification ( 210 X 297 mm) 39 464509 A7 B7 V. Measurement results of the () point of the invention. Bottom line readings are taken from a control group in areas of the sebum® that do not involve sebum particles. The data in Table 4 can be read in the same way as in Table 3. It is worth noting that the data in column 1 shows that because of its large amount of sebaceous granules, the measurement area shows poor blood volume below the value of 1, while the group that is not affected by sebaceous granules has only 6艏 Measured below 1. The topical application of the test sebum granules of the present invention to the jelly group effectively reduced the number of measurement points lower than 1, from 68 to 45 for 8 weeks, to 17 for 16 weeks after treatment. This number generally moves to the right * at weekly intervals, and further moves at 16 weeks, which shows that the improvement in blood volume is attributed to the beneficial effects of the sebum granule treatment composition tested. ^^ 1- ^^^ 1 1 ^ 1 tut n ^ iid ^ im — ^ ϋ ^^^ 1 n ^ i Λ, νβ (Please read the precautions on the back before filling this page) Employees of the Central Standards Bureau of the Ministry of Economic Affairs Cooperatives printed this paper in the standard China National Standards (CNS) A4 (2 丨 0X297 mm) 40 464509 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 5. Description of the invention () Table 5 uses laser doppl er transfer measurement withdrawal cycle thigh area circulation problem blood roll rate individual # 1 sebum granule stage 2/3 46 years old, before treatment 1.04 1.22 4.67 4.56 1.11 2.45 0.45 0.56 2.67 0.98 2.22 0.67 0.67 3.55 0.76 0.67 2.19 0.78 2.78 3.67 0.78 3. Π 0.88 2.55 3.56 2.67 3.42 5.6 8.89 5.66 Individual # 1 sebum stage 2/3 46 years old, 16 weeks after treatment 1.33 1.92 5.11 5.03 1.44 2.55 1.59 2.56 3,03 1.22 2.78 2.22 3. 12 4.03 1.33 1.87 2.45 1.44 3.11 3.99 1.12 3.84 1.09 2.77 4.03 3.04 4.30 6.15 6.89 5.88 (Please read the notes on the back before filling this page) This paper size is applicable to China National Standard (CNS) A4 size (2 丨 OX297 mm) -41- / 16 0 9 A7 B7 V. Description of the invention () Table 5 reports the composition of the sebum particles invention WH detailed study of the effect of a body. Relative blood radon measurements were reported to 2 痼 apparent data. Comparative measurements were taken at 30 places in this individual. The yield before treatment was reported in the upper half of the table, and the reading after 16 weeks of treatment was in the lower half of the table. Therefore, the reading at a specific position in the upper half of the table can be compared with the reading in the same position in the lower half of the table to determine the effect of the tested therapeutic composition, as in the comparison of "before use" and "after use" . With one exception, all readings improved after treatment. The exception is an unusually high yield of 8.89. This may be due to poor blood flow in the adjacent plaque area. All readings below 1 improved to above 1, and some of the improvements were significant. Therefore, the third praise in the second column improved from 0.67 before treatment to 2.22 after treatment. In addition, Table 5 shows a highly significant and comprehensive improvement in blood rolls over a wide range of thighs affected by sebum grains in a single body due to the improvement of structural microcirculation vessels caused by the treatment method of the present invention. (Please read the notes on the back before filling in this 筲) IV, ΐτ Form 6

Consumption cooperation between employees of the Central Bureau of Standards, Ministry of Economic Affairs, Du printed ultrasound analysis of the average thickness of 10 individuals, and measured the epidermis / dermal thickness epidermis / true density subcutaneous plaque domain thickness of each individual's thigh area test group &quot; f House density before 2.34 68% 4.12 33¾ After 8 weeks 2.56 74¾ 3.99 4 η After 16 weeks 3.12 82¾ 3.25 W21 This paper size applies the Chinese National Standard (CNS) Α4 specification (21 〇 × 29? Mm) 42 Central Bureau of Standards, Ministry of Economic Affairs Employee Consumption Cooperation Du printed Α7 Β7 V. Description of Invention () Table 6 shows that after 8 weeks of treatment, the thickness of the epidermis-straight skin epithelium increases and the subcutaneous part decreases. Both showed a significant increase in density. Further improvement was obtained after 16 weeks of treatment with the composition. These data show that the composition of the present invention provides a significant structural improvement in the condition of the skin, which can provide long-term benefits to the condition of the skin. τ Industry Application Capability The present invention is particularly suitable for the cosmetic industry to provide new formulas and methods for the treatment of sebum granules and pimples. When the illustrative embodiments of the present invention have been described above, various modifications that can be understood will be apparent to those skilled in the art. Such amendments are intended to be within the spirit and scope of the present invention * and are limited and defined only by the scope of the appended claims. (Please read the notes on the back before filling in this purchase) i-, 4

、 1T This paper size is applicable to China National Standard (CNS) Α4 specification (2 丨 〇 X 297 mm) Λ. -43-

Claims (1)

5 4 6 〇 # The original month EI supplement 9〇〇〇 〇5 4 B 4 8888 ABCD Printed by the Ministry of Economic Affairs Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 6. Application for Patent Scope No. 84108866 Patent Application for Amendment of Patent Scope Date of this amendment: July 30th 1. A pharmaceutical composition for improving the condition of sebum granules, which is intended to cause long-term high-volume penetration by continuous topical application to the skin area on tissues affected by sebum granules Epidermal water loss for a period from 8 weeks to the desired improvement of sebum particles, the composition contains, based on the weight of the composition: a)-a cosmetically compatible reduction of 1 to 15% Positive hydroxycarboxylic acids to increase water loss through the epidermis (TEWL); and b)-a retinoid cell regeneration / differentiation modulator with a ratio of 0.005 to about 6.0%. 2. The pharmaceutical composition according to item 1 of the patent application, wherein the TEWL is increased by at least 100% after 8 weeks of sustained application. 3. For example, if you apply for a pharmaceutical composition in the scope of the first item of the patent, the performance application of the composition is to be continued for another 4 weeks "4. If you apply for a pharmaceutical composition in the scope of the first item of the patent, the composition is effective Increase TEWL by at least 100%, and its application period is from at least 8 weeks to 26 weeks. 5. The pharmaceutical composition according to item 1 of the patent application scope, further comprising: c) a cerebroside barrier repair inhibitor at a ratio of 0.01 to 5% to prevent the repair of the skin water barrier. 6. For example, the pharmaceutical composition in the scope of application for patent No. 5 wherein the composition is in accordance with the national standard of the paper (CNS M4 specification (2 丨 0 X 297 mm)) ι ^ ϋ ml In, ^^ ^^ 1---n ^ i i4n 1 ^ 1 ^ h. (Please read the precautions on the back before filling out this page) Λ8 B8 C8 D8 Printed by the China Industrial Standards Bureau of the Ministry of Economic Affairs, China Industrial Standards Co., Ltd. «. 6 2. The scope of patent application shall be for topical application twice a day for at least 8 weeks. 7. The pharmaceutical composition of item 1 of the scope of patent application, wherein the composition contains 5 to 10% lactic acid, glycolic acid or salicylic acid, 0 to 3.0% of vitamin A palmitate, and one to 0.1% to 0.5% of a cerebroside substance. 8. For example, the pharmaceutical composition of the first scope of the application for a patent, wherein the composition can be applied to a selective Treatment of water barrier destruction in the following groups: peeling agent 'mechanical friction in application solutions, and solvent extracts of hydrophobic skin barrier ingredients. 9. A daily topical application on sebum granules to those affected by sebum granules A pharmaceutical composition on the skin area that effectively increases TEWL after 8 weeks of topical application 100% less, the composition contains, based on the proportion of the weight of the composition: a)-a ratio of 1 to 15% of cosmetically compatible pH-lowering hydroxycarboxylic acid to increase the moisture that penetrates the epidermis Loss (TEWL); and b)-one of retinoid cell regeneration / differentiation modulators at a ratio of 0.005 to about 6.0%. c) A cerebroside barrier repair inhibitor with a ratio of 0.01 to 5%, to inhibit the repair of skin water barrier. 10. The pharmaceutical composition according to item 9 of the patent application scope, which contains 5 to 10% of lactic acid, glycolic acid or salicylic acid, 0.3 to 3.0% of vitamin A palmitate, and 0.1 to 0.5% of one brain. Glycoside substances. '11. The pharmaceutical composition according to item 10 of the patent application scope, which comprises at least one optional ingredient selected from the group consisting of: a diuretic for stimulating blood flow ----------------- -_— Order ------ line (please read the precautions on the back to write this page) The paper size is in accordance with the Chinese National Standards (CNS) Λ4 wash case (2 丨 〇 × 297 mm) 5 4 :, 6 9 ο Printed by ABCD Central Consumer Bureau of the Ministry of Economic Affairs, Consumer Cooperatives 6. Application for patent scope agents, anti-allergic agents to control allergic reactions caused by the TEWL increasing agent or the cell regeneration / differentiation modulator And antioxidants, and mixtures of these. 12. A pharmaceutical composition for the treatment of sebum granules, comprising a TEWL increasing agent in an effective amount, a skin cell differentiation modulator, and a barrier repair inhibitor for inhibiting water barrier repair of the skin. 13. The pharmaceutical composition according to item 12 of the patent application scope, which comprises the TEWL increasing agent in a proportion of 1 to 15% by weight based on the weight of the composition. 14. The pharmaceutical composition according to item 13 of the application, characterized in that the proportion of the TEWL increasing agent is from 5 to 10%, and the TEWL increasing agent is lactic acid, salicylic acid or glycolic acid. 15. The pharmaceutical composition according to item 12 of the patent application, characterized in that the cell regeneration / differentiation modulator is a retinoid in a proportion from 0.005 to 6.0% by weight. 16. The pharmaceutical composition according to claim 13 of the application, characterized in that the barrier repair inhibitor is a cerebroside in a proportion of from 0.01 to 5.0% by weight. 17. The pharmaceutical composition according to item 12 of the patent application, characterized in that it contains at least one optional ingredient selected from the group consisting of a diuretic for stimulating blood flow, a control for the TEWL increasing agent or the cell Antiallergic and antihypertensive agents for allergic reactions caused by regeneration / differentiation modulators, and mixtures thereof. 18 · If the pharmaceutical product of item 12 of the patent application scope is characterized by including -3- this paper size is applicable to the national standard (CNS) A4 specification (210 X 297)! '', (^ Order * Line II (please read the notes on the back ^ · ν first write this page) Printed by the Consumer Cooperatives of the Central Government Bureau of the Ministry of Economic Affairs 46 45 0 9 Α8 B8 C8 _____D8 6. The scope of patent application is from 5 to 10% lactic acid. From 0.5 to 4.0% of vitamin A standard glutamate and from 0.1 to 0.5% of cerebroside. 19. The pharmaceutical composition according to item 12 of the patent application is characterized in that it is effective after 8 weeks of continuous administration Increasing TEWL by at least 100%. 20. A method for the preparation of a pharmaceutical composition for topical application to sebaceous granules affected skin areas in the treatment of sebum granules, the composition being administered topically after 8 weeks It can effectively increase TEWL by at least 100%, and the method is characterized by including the following components based on the weight ratio of the composition: a)-a cosmetically compatible ratio of 1 to 15% Lowering the pH of hydroxycarboxylic acids to increase water loss through the epidermis (TEWL); and b) -One of the retinoid cell regeneration / differentiation modulators at a ratio of 0.005 to about 6.0% c) A cerebroside barrier repair inhibitor at a ratio of 0.01 to 5% to prevent the repair of skin water barriers. 21. The method as claimed in claim 20, characterized in that the composition contains from 5 to 10% of lactic acid, glycolic acid or salicylic acid, from 0.3 to 3.0% of vitamin A palmitate and from 0.1 to 0.5% of cerebroside substance. 22. The method of claim 21, wherein the composition contains at least one optional ingredient selected from the group consisting of a diuretic for stimulating blood flow, a control for the TEWL increasing agent, or the Anti-allergic agents and antioxidants for allergic reactions caused by cell regeneration / differentiation formulations, and mixtures thereof. -4- The size of this paper is applicable to the country's national standard (CNS) A4 (210X297 mm) --------- ^ ------- ir '------ line' (Please First read the precautions on the back before filling in this tile) 464509 Α8 Β8 C8 D8 Consumer cooperation of the Central Standards Bureau of the Ministry of Economic Affairs Du Yinzhang 6. Application for patent scope 23. —A pharmaceutical composition for the preparation of sebum granules The method is characterized by including an effective amount of a TEWL increasing agent, a skin cell differentiation modulator, and a barrier repair inhibitor for inhibiting the repair of the water barrier of the skin. 24. The method according to item 23 of the patent application, characterized in that the composition contains a TEWL increasing agent in a proportion of from 1 to 5 wt% based on the weight of the composition. 25. The method of claim 24, characterized in that the proportion of the TEWL increasing agent is from 5 to 10%, and the TEWL increasing agent is lactic acid, salicylic acid or glycolic acid. 26. The method according to item 23 of the patent application, characterized in that the cell regeneration / differentiation modulator is a retinoid in a proportion from 0.005 to 6.0% by weight. 27. The method according to item 23 of the patent application, It is characterized in that the barrier repair inhibitor is a brain force in a ratio of from 0.01 to 5, 0% by weight. 28. The method according to item 23 of the patent application, characterized in that the composition contains at least one optional ingredient selected from the group consisting of: a diuretic for stimulating blood flow 'to control the TEWL increasing agent or the Antiallergic agents and antioxidants for allergic reactions caused by cell regeneration / differentiation modulators, and mixtures thereof »29. The method according to item 23 of the patent application, characterized in that the composition contains from 5 to 1 0 ° /. Lactic acid 'from 0.5 to 4.0% of vitamin A palmitate and from 0.1 to 0.5% of cerebroside. 30. The method of claim 23, wherein the composition is effective to increase TEWL by at least 100% after 8 weeks of continuous application. The dimensions of this paper are in accordance with Chinese Goods Standards (CNS), M Grid (2ίΟΧ 297 stitches)---I-----1— I. nn a ^ — nn ^ 1. ^ 1 '一 eJ (Please first Please read the notes on the back of the page and fill in this page again) Amendment Notice This month, the application date η. 1 fire case No. 1 — tit "S ί 'category k έί K Va The above columns are filled by this bureau) A4 C4 464509 No. 84108866 Amendment page of the invention patent specification Date of amendment: Year of printing ^ Chinese pharmaceutical composition for ameliorating a cellulite condition is called English a pharmaceutical composition for ameliorating a cellulite condition Residence, Residence Name: (Name), No. 46, Wacker Road, New Kanana, Connecticut, U.S. Boxes · U.S. Applicant's Residence, Domicile (Office) Representative Name Roger * Burgadou, 8787 Steinmon Highway, Milas, Texas, USA Paper Size GM China® Flap (CNS) A4 specification (21 × 297 mm) A7 B7. Step-Ministry of Central Standards Bureau, J-Consumer Cooperative, printed 464509 5. Description of the invention (i) The present invention relates to the topical application of sebum granules, including the composition And method, when it is used for a long time, if it is applied daily for several months, it can produce a structural improvement in the condition of sebum particles. The term sebum particles refers to the abnormal accumulation of a large number of fat cells under the skin | The unsightly part of the visual discontinuity. Sebum is a term coined by Nicole Ronsard in the 1970s (see Webster's New Universal Unabridged Dictionary, 2nd edition, Dorset Baber i983) to describe the abnormal subcutaneous fat mass. Accumulation causes a wide range of unsightly barriers to the normal smooth curve of the skin. Physiologically speaking, sebaceous granules are caused by the microcirculation of fat accumulation sites in the body. Serious sebaceous granules are characterized by the degradation of subcutaneous blood vessels, Poor blood flow, thinning of the epidermis and dermis of the skin, and in the subcutaneous area the hard mass of fatty substances surrounded by proteins And the accumulation of body fluids. As a result, the skin has an "orange peel" appearance. Sebum particles most often cause problems in the thighs, buttocks, and upper arms, and are less common in the outer limbs, back, trunk, and center of the corpus callosum, and on the face and neck. It is usually not noticeable on the hands and feet. Sebum particles are often associated with obesity, but they also appear on the skin of individuals of normal or near-normal weight. It is more common in women than in men, and it is more common in Caucasians than in darker-skinned individuals. Due to the serious damage to the appearance of individuals, the skin granules have far-reaching psychological effects, hurt the self-esteem of the affected individuals, and are not conducive to the healthy psychological development of young men and women. Therefore, there is a great need for effective treatment of sebum particles. Known methods for treating sebum granules include local mechanical action. The local scale of the paper is generally the standard Chinese national standard (ΓΝ5) Λ4 size (210X297 gong) (please read the note on the back before filling in this page) * 1T ^ Printed by the Central Standards Bureau Shoulder Workers Consumer Cooperatives 5 45 0 9 a? __B7 ............... 5. Description of the Invention (3) Caffeine I Theophylline and other xanthines appear to be effective as diuretics and to promote fat metabolism at high concentrations. Aminophylline, currently a well-known active ingredient of thigh cream or thigh smoothing cream, seems to be effective as a strong diuretic to promote lymphatic drainage, but has been reported to have significant toxic side effects (See Merck Index, 11th edition, Merck &amp; Co. Inc. 1989 Monograph No. 477). These agents do not take into account structural defects in the skin and blood vessels. U.S. Patent No. 5,030,451 to Trebosc et al. Describes some cosmetic compositions containing an improved caffeine derivative as an active agent. According to Trebosc et al., Column 9, lines 15-20, the disclosed formula has "good and long-lasting 'fat-breaking properties'" and thus has proven very effective in slimming programs and treating sebum particles. &Quot; However, No valid data has been reported. In column 1, lines 61-65 &gt; Trebosc et al. Taught the faster rate of subcutaneous penetration and confirmed the superiority of these agents in treating sebum particles. Mausner US Patent No. 5 No. 21,759 refers to the use of methylsilanol theophylline acetate alginate and methylsilanol mannuronic acid for anti-sebum granules. Without descriptive disclosure, the effect of such substances is assumed to be Equal to diuretics. One disadvantage of marketing stimulant compositions (containing caffeine, aminophylline or related agents as active ingredients) for the treatment of sebum granules is that medication problems will prevent them from being included in pharmacies Ready-to-sell cosmetic composition. Long-term repeated use may cause harmful side effects, and government regulations will restrict marketing. Another disadvantage is that this kind of medicine _____ _ 6 & q uot;. _ This paper size applies to Chinese National Standards _ (CNS) M specifications (2ΙΟχ: 297 cm) (Please read the notes on the back before filling this page), 1Τ 4 5 45 0 9 A7 B7 Llti Warp Ministry of Health, Central Bureau, Prospective Staff, Consumer Cooperatives, Printing Co., Ltd. V. Invention Description (The agent does not take into account the structural problems of skin and vascular defects. Scrub particles mechanical action, remove the outer layer of treatment, smooth the treatment surface tt and stimulate treatment update, but failed to Promote lymphatic drainage, long-term microcirculation degradation or fat metabolism. Frosted particles are hard particles, usually suspended cream or glue, which are rubbed or massaged to achieve mechanical exfoliation. The particles are usually polyethylene balls However, natural particles such as crushed peaches or apricot kernels have also been used. The disadvantage of these products is that it is difficult to control allergies. Topical retinoids, such as US Patent No. 5,051,449 to Kligman, can have Limit the improvement of sebum granules. Kligman has published a qualitative report comparing the efficacy of a topical retinoic acid formula with an unnamed non-medical cream after more than 6 months Efficacy described includes skin thickening, increased number of new blood vessels, and measurable moderate to significant improvement using pinch test (column 6, lines 50-61). No quantitative data were provided Therefore, the skilled artisan cannot determine the value of Kligman's sebum treatment. Many people hope and expect that sebum treatment will be more effective than moderate improvement after 6 months of treatment. The concentration of retinoic acid administered must be limited To avoid allergies (see column 2 of Kligman, lines 59-60), it is not possible to achieve sufficient efficacy by increasing the dose • The retinoic acid treatment method does not provide a long-term treatment that is satisfactory for sebum particles, and more Effective topical treatment. Contrary to Kligman's unfounded induction, my quantitative clinical research found that after 3 months of daily treatment, retinoic acid did not cause significant skin thickening. Therefore, there is a need for an easy-to-apply sebum treatment that provides structural improvement in a reasonable amount of time. The size of this paper is Shizhou China. ((::?) / \ 4 size (210 &gt;: 297 feet) (Please read the notes on the back before filling this page), 1T A7 B7 J6 45 Ο 9 V. Description of the Invention (The present invention, as applied for a patent, is intended to provide a treatment method. It solves the problem of providing an easy-to-apply topical sebum granule treatment method that can be marketed to consumers more effectively than previously obtained methods, and It can cause obvious structural improvement in a reasonable time. The present invention also solves the problem of providing a local sebum granule treatment method that can produce gradual and structural improvement when it is continuously used for a long time, and the preferred embodiment promotes the body to suffer The skin of the affected area of sebaceous granules is obviously thickened and the tissue is strengthened, the thigh and thigh circumference are reduced, and the microcirculation blood flow is increased. The present invention solves the above problems by providing a sebum granule treatment method, which is applied to the skin affected by sebaceous granules. The tissue destroys the water barrier properties of the skin in this area for a long time, which is enough to stimulate the renewal of the treatment and the regeneration of blood vessels to achieve enhanced effects. The barrier is difficult. Of course, this method of destruction cannot be strong enough to damage the sensitive dermis layer of the skin, or cause pain or significant allergies. However, in order to obtain the efficacy of the present invention, the treatment should provide a long-lasting effect of destroying the barrier, Not temporary effects. Because the normal function of the barrier is necessary for survival, destroying the barrier will cause a natural response to quickly repair the barrier. In more detail, within a few weeks of extended treatment, such as 8 weeks or more The barrier effect is continuously damaged and the increase in water loss penetrating the epidermis can be used to monitor the barrier effect. TEWL was measured after 12 weeks of treatment, and at least 8 hours after the last treatment, known sebum particles other than retinoids were found Therapeutic methods have very little sustained effect on the barrier effect, some seem to reduce TEWL. Retinoic acid, a peeling agent, and at least another exfoliating agent, only show TEWL at 12 weeks. This paper is scaled to Chinese national standards. ((: NS) Λ4 Specification UIOX 297) (Please read the notes on the back before filling out this page) '1Τ Printed by Consumers Cooperatives A7 B7 Fifth Ministry of Economic Affairs Central Cotton Standards Bureau Consumer Cooperatives Cooperatives M 464509, Description of Invention (8) Skin moisture loss. Generally this treatment is applied once or twice a day. Many new sebum granule treatment methods Various local mechanical treatments for the skin, such as scrubs, roughening or extraction or solvent extraction treatments, both treatment methods are applied violently or aggressively to increase TEWL by 100% or more as described above and maintain it for a long time. However, preferred methods of treatment include a chemical composition that can be applied topically, preferably in the form of a softener or cream, and that maintains an increased level of TEWL at a frequency of no more than one or two applications per day. The urgency of the method of treatment of the present invention must be controlled so that it can be accepted over a period of weeks or months without causing severe or painful allergies, redness, peeling or excessive discomfort. However, many people can tolerate the short-term appearance of these symptoms. Another aspect of the present invention provides a sebum granule composition comprising a TEWL increasing agent capable of increasing TEWL immediately or short-term, and a barrier-damaging agent which acts to maintain the increased TEWL level. Preferably, the composition also includes a skin lipid inhibitor, to prevent premature reconstruction of the water barrier and enhance the therapeutic effect of the composition on the sebum particles. In a preferred embodiment of this aspect of the invention, the TEWlJf additive is a cosmetically compatible hydroxycarboxylic acid with a reduced pH, preferably has the properties of a peeling agent, and is at least moderately soluble in water or hydrogenated alcohol Enables inclusion in a cosmetic composition. Such acids include alpha-hydroxycarboxylic acids, especially such as lactic acid and glycolic acid, and other hydroxycarboxylic acids, such as 2-hydroxycarboxylic acid, especially salicylic acid. The effectiveness of these acids seems to be related to their ability to lower the skin's intercellular fluids. The acid used and its concentration are chosen to achieve the desired increase in TEWL without causing excessive hypersensitivity. (Please read the notes on the back before filling this page) Order-11-Correction too A 3 days | 4 6 4 5 0 9 This year a H A5 Supplement 90. 7. 20 B5 IV. Abstract of Chinese Invention (Invention of Invention Name: The pharmaceutical composition used to improve the condition of a sebum granule shows a new topical sebum granule treatment by structural comparison in the thigh area affected by sebum granules, followed by structural improvements, including thickening of skin, Thigh formation and thigh contraction. The disclosed treatment method disintegrates the wall of Pillu water and increases the water loss through the epidermis (TEWL) for long periods of time or months, and includes mechanical or solvent effects such as Band analysis or acetone rinsing. A better treatment method uses a cream, which contains active ingredients such as lactic acid to increase TEWL *-a retinoid * preferably vitamin A palmitate to break down the establishment and extension of the barrier The increase of TEWL, and a kind of cerebroside to inhibit the synthesis of lipids and strengthen the increase of TEWL. Diuretics, for the immediate progress of beauty treatment, anti-allergic agents and antioxidants to control the allergic reaction, are other components that can be added. Ying Zhang Summary of the invention Title of the invention: a pharmaceutical composition for ameliorating a cellulite condition Printed by the Shellfish Consumer Cooperative of Zhongli Bureau of the Ministry of Tao «. --------- I l Install I (Please read the notes on the back before filling (Each page on this page) IT line New topically applied treatments for cellulite are shown by ^ comparative data to effect structural improvements in cellulite-afflicted thigh area tissues including skinthickening, thigh-firming and thigh-reduction. The disclosed treatments disrupt the skints water barrier and elevate trans-epideriaal water loss (TEWL) for extended periods of weeks or months and include methods of mechanical; or solvent action, for example, tape stripping, or acetone-washes .Preferred treatments use creams with active ingredients such as lactic acid to elevate TEWL, a retinoid ,! preferably vitamin A palmitate to disrupt barrier rebuildingj and prolong elevation of TEWL levels, and a cerebroside to 丨 inhibit lipid synthesis and intensify. The TEWL elevation. Diuretics, for immediate esthetic improvements; anti-irritants and anti-oxidants for irritation control are optional ingredients, the paper ft scale uses the national ladder (CNS) A4 wash grid (2 丨 0X 297 mm) 5 4 6 〇 # 正 年月EI added 9〇H〇09 〇5 4 B 4 8888 ABCD Printed by the Ministry of Economic Affairs Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 6. Application for Patent Scope No. 84108866 Patent Application Amendment of Patent Scope Amendment Date: 30 years 7. Month 1. A pharmaceutical composition for improving the condition of sebum granules, which is provided by continuous topical application to the skin area on tissues affected by sebum granules to cause long-term high-volume water loss through the epidermis for a period from 8 to 8 From week to until the desired improvement of sebum granules, the composition contains, based on the weight of the composition: a)-a ratio of 1 to 15% of a cosmetically compatible hydroxycarboxylic acid that reduces the positive value to increase Loss of water through the epidermis (TEWL); and b)-one of retinoid cell regeneration / differentiation modulators at a ratio of 0.005 to about 6.0%. 2. The pharmaceutical composition according to item 1 of the patent application, wherein the TEWL is increased by at least 100% after 8 weeks of sustained application. 3. For example, if you apply for a pharmaceutical composition in the scope of the first item of the patent, the performance application of the composition is to be continued for another 4 weeks "4. If you apply for a pharmaceutical composition in the scope of the first item of the patent, the composition is effective Increase TEWL by at least 100%, and its application period is from at least 8 weeks to 26 weeks. 5. The pharmaceutical composition according to item 1 of the patent application scope, further comprising: c) a cerebroside barrier repair inhibitor at a ratio of 0.01 to 5% to prevent the repair of the skin water barrier. 6. For example, the pharmaceutical composition in the scope of application for patent No. 5 wherein the composition is in accordance with the national standard of the paper (CNS M4 specification (2 丨 0 X 297 mm)) ι ^ ϋ ml In, ^^ ^^ 1---n ^ i i4n 1 ^ 1 ^ h. (Please read the precautions on the back before filling in this page)