TW419375B - Hydroxypropyl methylcellulose ether compositions for reduction of serum lipid levels - Google Patents

Abstract

The present invention concerns cool-water dispersible powder formulations comprising high molecular weight hydroxypropyl methylcellulose which has been milled to a specified particle size, with or without encrustation or other surface treatment, for dispersion into consumable liquids or for formulation as dry-mix powders, sauces, instant set puddings and baked goods for human consumption. The formulations are used for reduction of serum cholesterol levels. A process for preparing the formulations and their mode of administration are also provided.

Description

Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 419375 A7 _____B7_ V. Description of the invention (1) The present invention is a dry powder and dry mixed formula of hydroxypropylmethyl levulinin composition with water-soluble and high viscosity grade For non-systemic use to reduce serum lipid levels, especially serum cholesterol, and LDL1 sterol levels. The use of streptavidin in edible compositions, especially pharmaceutical products, is well known. The common function of cellulose ethers in such applications is as a controlled release agent. In general, however, this type of application requires only a very small amount of ferritin ether, representing only a small percentage of the total formulation. It is currently known that polyfluorene compounds can be used to lower the level of human blood plasma membrane sterols. However, many of these compounds, including systemic and non-systemic compounds, have adverse side effects or have properties that make it difficult for patients to follow their use. For example, it is known that the characteristics of unstructured compounds such as sandy, gravelly, irritating throat, difficulty in dispersing, and phase separation make it difficult for patients to follow. Therefore, the search for new non-systemic compounds that can be used to lower the level of steroids in human serum continues to be an important area of research. The sterol tyramine system is an important non-systemic compound known to be effective in treating high blood steroid levels (also known as hyperspectrolemia). It is thought to cause multiple cases of human sclerosis . Stenol tyramine, which is generally taken orally to achieve its effect of reducing or controlling cholestyrase *, is astringent and difficult to swallow. Zanthomycin also has side effects that cause constipation. Methods and compositions that include testosterone tyramine are known, as described in liS-A-3,30S, 020, US-A-3,383,28 and US-A-3,499,960 and US-A-3,947,272 People 0 Known that plants that are substantially soluble in water follow Weiru Ruqian, guar, and moon ------------ • equipment ----- 1T ------ ^ (Please read the notes on the back before filling this page)

Chinese National Standard (CNS) A4 Regulation (210X29? Public f) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 419375 A7 B7 V. Invention Description (2)-Glucose can show the effects of reducing sterols, but these Soluble fibers are not very effective per gram. At the same time, because these soluble plants can be easily metabolized by colonic bacteria (causing a large amount of anaerobic production of methane, carbon dioxide, and hydrogen), it is known that when these plants are administered in an effective dose for kappa therapy, they may cause Heavy flatulence, bloating, and very uncomfortable abdominal discomfort. Furthermore, psyllium seed shell pods are generally contaminated with fragments of protein shell pods, and allergens known to be related to psyllium are expected. It has been confirmed that milled psyllium millet has the ability to lower the serum cholesterol level of patients. Ερ-Α-0 326 926 describes that the use of products containing psyllium asiatica shell pods can effectively lower human serum cholesterol levels. Ερ-Α-0 309 029 Syrian biscuit containing psyllium and fatty alcohols can help lower blood cholesterol levels. Ερ-Α-0 323 666 describes the use of products containing sterol tyramine, combined with psyllium or polyzyme and fat, which can be used as oral administration to reduce the steroid composition. Recently, it has been used as a sterol reducing agent The various forms and formulations of propyl methylstilbene (HP MC) have been discussed (eg WG-A-US92 / 01515 and WO-A-US92 / 01511). US-A-5,281,584 discusses baking formulations for similar uses. Although these references use HPMC with a high number of average molecular weights, the formulation is not mentioned in the present invention. Previously, vitamine ethers, such as carboxymethylzinovidin and methylzinodin, were in the form of medicine nine, powder (such as EP-B1-0 119 479), and suspensions in highly dextrose solutions. Used as a large laxative. There are significant differences between these follow-up ethers and the HPMC of the present invention (such as chemical structure, molecular placement, and paper size applicable to the Chinese National Standard (CNS) Λ4 specification (2 i 0 X 297 mm), binding ice (please (Please read the notes on the back before filling this page) 419375 Printed by the Consumers' Cooperative of the China Standards Bureau of the Ministry of Economic Affairs A7 B7 _V. Description of the Invention (3) Adhesiveness) and its use. In order to administer non-centralized compounds, as discussed above, a suitable formulation should be sought. Formulations of these vitamins are not easy to prepare for a number of reasons. For example, the pentamidine ether in the medicinal form does not disperse and dissolve immediately. The peripheral part of Yaojiu quickly forms gelatinous water and coatings of the water and cellulose M, which inhibits the decomposition of Jiujiu and slows down the water and action inside Jiujiu seriously. Therefore, the pill is often discharged in the form of a complete gel covering substance. Therefore, when used in the form of drug nine, the efficacy of stigmatin was significantly reduced. British Patent No. 1,280, 150 teaches that blending insolectin and 1 to 20% of water-soluble foods, such as sucrose, can help dissolve ether dissolve in cold water without forming a mass. "This is an attempt to improve early Known vitamine ether formulations containing covalently bonded glyoxal. Glyoxal is disadvantageous because it is toxic when digested. ΕΡ-Β-0 119 479 describes a large laxative, which imparts 2 grams of fine powder of 100,000 cP viscosity grade hydroxypropylmethyl levulinin to about 25 grams of Tang " * orange flavored beverage blend (from (Distributed by General Foods Corporation of White Plain, New York, U.S.A.), providing formulators of therapeutic vitamins in therapeutic doses for constipation. Various celluloses have been used as large laxatives. Among them, a concentrated kneaded sugar solution was first prepared in water, and then the molybdenum K was dispersed therein. This method is used to minimize the overall hydration and decomposition of the stilbene ether and to minimize the increase in viscosity. (For example, see US-A- This paper applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) _ [_ ---:-: --- -------------- order- ----- (Please read the note on the back first and then fill out this page) Printed by A7 ____B7_ of the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives V. Invention Description (4) 2,701,782. However, this type of suspension Very thick and semi-gelatinous, has a sticky texture, is very sweet, and is therefore not attractive to patients. U.S. Patent No. 5,266,334 to Depak Phadke et al. Discloses a sugar-free powder mixture of maltodextrin and methyllevavidin or hydroxypropylmethyl divitamin for use in large laxative formulations. It has been taught that this strand of vitamin E exists as a powder in the blend, rather than a substance with an M-coated outer skin. The size of the hydroxypropylmethyl stimulant is less than 40 旆 (400 m m), and preferably less than 60 sieve (250 w a). U.S. Patent No. 5,266,334 to Dhiri n Shah et al. Teaches the preparation of sucrose-coated low-molecular-weight methylsilvezin, in which the ratio of methylpanvidin to sucrose is 2: 1, and the dry powder has the same consistency as fine flour . The dry powder is prepared by the method described in the patent * cannot be directly dispersed in water without causing gelation, and requires a "carrier" formulation Evidence of the unpalatability of conventional compositions * is a well-known low adherence rate for patients who require a daily diet of such compositions. This low adherence rate indicates that the absolute box is more delicious and effective in controlling blood cholesterol composition than the known composition. The present invention deals with the non-compliance problem by providing a suitable formula by using the composition in the method of lowering the serum sterol level of a patient, thereby enhancing the effectiveness and promoting of the hydroxypropylmethylcarbamidine. Patient compliance. The present invention is a dry powder composition that is dispersible in cold water. It is not systematically milled to a high molecular weight with a specific particle size distribution (-binding knowledge (please read the precautions on the back before filling this page) ) This paper size applies to one Chinese standard (CNS 丨 A4 specification (210 × 2K mmΐ 419375 A7) Consumption cooperation by employees of the Central Standards Bureau of the Ministry of Economic Affairs. Du B__5. Description of the invention (5) HMW) Hydroxypropylmethyl Vitamins, with or without skin effect or other surface treatment, are dispersed in edible liquids or used in reconstruction of dry mixtures, sauces, puddings, and baked goods. Serum oxysterol level of mammals, especially humans. Also provides the preparation and its administration method. A dispersible, dry powdered hydroxypropylmethyl relay composition in cold water according to the present invention includes: A hydroxypropylmethyl hydrazone having: (a) an upper limit of hydroxypropylmethyl strand particles having less than or equal to 5: ζ greater than about 600 μB and having an upper limit of less than or equal to 50: £ Hydroxypropyl a The particle size distribution of the basic strand dimension particles is less than about the lower limit of about 180 wa; and (b) has a viscosity greater than 10,0O0cP to 2, QOO, OOOcP in an aqueous solution of 20 = 2% by weight or less. The above-mentioned hydroxypropyl group Methylstilbene has an epidermal-imparting agent such as sucrose, maltodextrin, or other epidermal-imparting agents. The composition of the present invention can be used to lower the serum lumen sterol level of non-ruminant mammals, especially humans, who require such treatment. The method includes administering from about 1 to about 8 grams of the above-mentioned hydroxypropylmethyl hydrazone composition per dose to the mammal, with or without imparting an outer skin effect. The preparation method of the aqueous dispersion requires only gentle mixing in cold water, which includes: a) grinding, milling, or sieving a high molecular weight hydroxypropyl methylsulfonium to obtain particles having less than 50 × and less than about 180 «A and particle size distribution of particles less than 5¾ greater than about 600 W: and (please read the precautions on the back before filling out this page) The dimensions of this paper are applicable to China National Standards (CNS) A4 specifications (common t) Ministry of Economic Affairs Central Bureau of Standards Shellfish Consumption Cooperative printed △ 19375 A7 B7 V. Description of the invention (6) b) Optionally, M- 棰 Natural sugar or maltose paste box can be applied to the outer skin agent High molecular weight hydroxypropyl methyl hydrazone is applied to the outer skin and the outer skin The weight ratio of the agent to the hydroxypropylmethyl hydrazone is from about 0.5: 1 to 2: 1, and then the hydroxypropylmethyl woven fabric imparted with the skin is passed through a sieve with 16 sieve holes; and c) optionally adding a flavoring agent; and d) optionally adding one or more selected from the group consisting of anticorrosive thinners, tinctures, colorants, anticaking agents, antioxidants, sunscreens, vitamins, mill substances and coagulants Additive substances. The formulation of the present invention provides highly water and pre-dispersed high molecular weight (HMW) hydroxypropylmethyl relay (HPMC) without the need for hot water dispersion Glue temperature). In the composition of the present invention, the hydroxypropylmethyl levulinin exists in the form of a human taking a child daily from about 2 g to 30 g. For the purposes of the present invention, the terms used herein are defined below. "Hydroxypropyl methylcellulose (HPMC)" refers to a hydroxypropyl methyl woven fabric having a number average molecular weight greater than about 80,000 Daltons (10,000 cP viscosity grade). The hydroxypropyl methyl paper fabric of the present invention The "high molecular weight" of the ethers refers to the hydroxypropylmethyl line retinoids having a number average molecular weight of greater than about 80,000 Daltons. The hydroxypropylmethyl line retinoids having a number average molecular weight of greater than about 150,000 Daltons Type K, which is said to have ultra-high molecular weight (UHMW). The number average molecular weight of the hydroxypropylmethylpyrene used in the present invention is preferably greater than about 100,000 Daltons, more preferably greater than about 140,000 lanes ----------------- Order -------- (please read the precautions on the back before filling this page) This paper size applies to Chinese national standards (CNS ) A4 is present ("mm 419375 A7 B7 V. Description of the invention (Dalton, and preferably greater than about 150,000 Daltons. Hydroxypropyl methylkinin ethers have a number average molecular weight of less than or equal to 400,000 Daltons Upper limit. The type of hydroxypropylmethyl starvin used in the present invention has a value from about 19 X The methoxy substitution to 24 X, and the hydroxypropoxy substitution from about 4 to 12%. 0 The following table is shown. The number of average molecular weights versus viscosity grades is shown in the table below. The number of average molecular weight viscosity grades η, Dalton cP 80, 000 10,000 100,000 25, 000 140, 000 50, 000 150,000 100, 000 220, 000 400, 000 260, 000 500,000 400, 000 2, 000, 000 Printed by the Employees' Cooperative of the China Standards Bureau of the Ministry of Economic Affairs The hydroxypropyl methyl hydrazine of the present invention is a high viscosity grade or a person with a high viscosity. "" High viscosity grade "or" high viscosity "is a dragged vitamin. It is shown at 20t in a 2 weight percent aqueous solution: greater than Viscosity of about 10,000 centipoise (cP) (10,000,00 ^ 1 & .3) * and viscosity up to 20,000 < ^ (20.000 aPa.s). The viscosity can generally be used conventionally The method measures the cost, for example, by measuring the concentration of the polymer in the aqueous solution of the desired degree in a Ubbelohde thin viscosity meter tube at a specific temperature. The Burmese prime of the present invention is shown to be greater than About 10,000 cP (10.000 aPa.s), preferably from about 25,000 cP (25,000 ffiPa .s), — r! n IIII nn Order ~~ ^ (Please read the notes on the back before filling in this page) The paper size is in accordance with the Chinese National Standard (CNS) A4 specifications 212 X Z9? mm 10 Ministry of Economic Affairs Printed by the Central Consumers Cooperative Bureau Consumer Cooperative 419375 A? B7 V. The viscosity of invention description (8) to about 2,000,000 cP (2,000,000 mPa.s). More preferably * The lysin K of the present invention exhibits a viscosity in a 20 t! 2 weight percent leech solution from greater than about 50,000 cP to about 80,000 cP, most preferably from about 10,000,00. Cobalt degrees from cP (100,000 aPa.s) to about 500,000cp (500,000 aPa.s). Conversely, "low viscosity grade" means that the visvenil ether shows a viscosity of less than about 10,000 cP (10,000 mPa.s) at 2o in a 2% by weight S aqueous solution. For the purpose of the present invention, the milling and sieving of the hydroxypropylmethyl dysvinate composition can be performed with any apparatus capable of achieving a specific particle size distribution and not subjecting the composition to heating at 50 TCM. For the preparation of hydroxypropyl methylcellulose fluff, an Alpine fan impact mill equipped with a sieve with a diameter of 0.4 am provides satisfactory results. A variety of other milling strength mechanical impact mills can provide similar results, including hammer hammers, bolts, hammers, and knife mills. For the preparation of granular derivatives, milling the dried dermal hydroxypropylmethyl levulinin through a Fitz brand mill with an appropriate mesh size can provide the required particle size distribution. When the hydroxypropylmethyl levulinin of the present invention is milled and / or sieved until it has the desired particle size distribution *, the hydroxypropyl methyl levulin is formed as a pharmaceutically active ingredient. The pharmaceutical constituents are white villi-like solids with a specific particle size distribution, and are referred to herein as "pimples" or the " pharmaceutically active constituent β. It is called "granular" when it is used to improve the fluff by imparting a skin-coating agent so that the hydroxypropylmethyl paclitaxel has a skin-coating component and is milled and / or sieved to achieve a desired particle size distribution. derivative". When the fluff or the granular derivative and other components ----..-------- install -------- order ------- know (please read the precautions on the back first) Refill this page} National Standard (CNS) Λ4 specification (210X297 mm) for this paper size 11 Central Consumers Bureau of the Ministry of Economic Affairs, Consumer Cooperatives Printing Poly 419375 A7 B7 V. Description of the invention (9) Ingredients are blended to get the final result In the form of the agent fi, it is referred to herein as a "formulated product." When referring to all or any of the forms (such as fluff, granular derivatives, and formulated products), it is referred to herein as a "composition." The composition exhibits palatability in the formula product (especially the drinkable formula product). The particle size distribution of hydroxypropylmethylpanapolin fluff is important. The upper limit of the particle size distribution of the required fluff has less than Or equal to 5¾ (S 52) of hydroxypropylmethyl levulinin particles larger than about 600 «a (0.6b ·, No. 30 mesh sieve), and preferably less than 2JS; larger particles cause the formulation product liquid The nature of grit in the form of. The lower limit of the particle size distribution of fluff is 505 or less: (< 50 2) The hydroxypropylmethyl followin particles are less than about 180 «* (0.18 · β, 80 mesh sieve), and preferably less than about 40 × * and more preferably less than about 30%. When the formula is dispersed into water or other liquids for consumption, small particles will cause foam, air bags, rough irrigation, and rapid viscosity increase. The above mesh size is the size of the US sieve "AS ™" -EU-61. When the ultra-high molecular weight hydroxypropyl methyl hydrazine milled to the traditional fine powder (100,000 cP viscosity grade, 80X through 80 mesh sieve) is added to the baked product (such as 25- When 30 grams of biscuits contain 5 grams of hydroxypropylmethyl arsonin), when dried, the dryness turns into chewing sugar. For the purposes of the present invention, the result is unacceptable for the formula product. However, When the same hydroxypropylmethylvindin is milled through a 0.4 nn sieve of an Alpine mill, fluff is obtained. The surface area of the fluff is much smaller than that of traditional powder. When the fluff is added to a biscuit (such as 25- When 30 grams of biscuits contain 5 grams of hydroxypropylmethylstrinolide fluff), the biscuits can be scooped And pharyngeal and substantive, this paper size applies Chinese National Standards (CNS) Λ4ΐΙ grid (: 10 X mm; -I 1 to order I,-^ (Please read the precautions on the back before filling this page) 12 419375 Economy Printed by the Consumers' Cooperative of the Ministry of Standards, Ministry of Standards, A7, B7 5. The invention description (w) is not sticky. Therefore, it significantly improves the palatability. When it is milled to the traditional fine powder U00,000cP viscosity grade; 80X pass 80 No. mesh sieve; 2.5 to 5 g) of ultra-high molecular weight hydroxypropylmethylretinoin was dried and dispersed to 2 δ g of orange-flavored beverage mixture powder. At the time, it was only slightly dispersed at a concentration of 2.5 g, and agglomerated heavily at a concentration of 5 g. Conversely, when the hydroxypropylmethylzantrolose fluff of the same viscosity grade was dried and dispersed to 28 g of gardenia-flavored beverage mixture powder, when mixed with 250 ml of cold water, the formula product was instantly dispersed at a dip concentration. The composition of the present invention provides a hydroxypropyl methylcellulose form * which is instantly dispersible in cold water (0-20 TC) and is suitable for preparing from 1 to S grams per dose * preferably from 2 to 5 grams * The hydroxypropyl methylammoniolide is a palatable oral preparation that is administered orally to treat elevated serum cholesterol levels. The amount of hydroxypropyl methyl hydrazine that is dispersible in water is surprising and far exceeds what was previously thought to be possible before holding a palatable formulation. The advantage of the velvet form of hydroxypropylmethyl-inosectin is that it can be sent to the supper in a highly hydrated and dispersed form * without relying on the hydroxypropylmethyl-inosin Food dosage form or hot water / hydrothermal cross-body dispersion. In this section, "foodstuff" refers to the inclusion of hydroxypropylmethyldividin in baked patties or crusts *-generally including about 5 grams of hydroxypropyl in baked goods with a weight of about 25 to 35 grams. Methyltin. The food can be simmered with about 8 ounces (225 grams) of water or other liquids. Also in this section, the "hot water" or "hot liquid" dispersion system is at a temperature of about 851 or more. The paper size of the paper is generally in accordance with China National Standards (CNS) 8 (4) (格 ΙΟ × 297 mm) (please first Read the notes on the back and fill in this page). Packing · Order-13-Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 419375 A7 _______B7_ V. Description of the invention (11) Degree dispersed into water or other liquid (such as squeezed lemon juice , Cocoa, and hot chocolate). The temperature is higher than the known thermogel temperature range (50-70 υ) of hydroxypropylmethyl fervidin. Hydroxypropylmethyl fluorescein fluff form enable Administer hydroxypropylmethyldividin in a delicious and expensive form of about 1 gram per dose, especially greater than 3 grams per dose, and more specifically 5 grams per dose or more. M injections are encouraged to maintain sufficient palatability. M encourage patients It is difficult to achieve the dosage of this type of hydroxypropylmethyl viloxanthin. Very unexpectedly, although the particle size of hydroxypropylmethyl sulfonamide fleece is large, it does not appear when it is dispersed in aqueous liquid. Gravel-like fluff form allows hydroxyl groups The methyl hydrazine is first hydrated for oral administration and the fact that the formula containing the dry fluff can be fat-free and 1 sterol is very important for any non-systemic sterol therapeutic formulation. The considerations. Therefore, the composition and the formulated product have significant advantages over those previously known. Alternatively, the hydroxypropyl methylhydoxylin fluff can be coated with S and M to give the outer skin ingredients a granular derivative. The The outer skin-imparting agent can be natural sugars, such as sucrose, glucose, fructose, corn syrup solids, etc. Among them, M sugar is preferred. When natural sugars are used, the outer skin component is given. About 0.25: 1 to about 4: 1 (weight / reset), preferably from about 0.5: 1 to about 3: 1 (heavy child / weight) * more preferably from about 0.75: 1 to about 2: 1 (weight fi (Weight / weight), preferably about 1: 1 (weight / weight). The skin-imparting agent may also be selected from low molecular weight sugar polymers and sugar derivatives and mixtures thereof, such as maltodextrin, sorbitol, etc. Hydroxypropyl Methyl -------- Ί ------ ΐτ ------ (please read the precautions on the back before filling this page) Free use of Chinese National Standards (CNS); \ 4Specifications 210X297, Epidemics 14 419375 V. Description of the invention (A7 B7 12 Comparison of velutin and villi printed by the Central Standards Bureau of the Ministry of Economic Affairs, Masonry and Consumer Cooperatives, for imparting outer skin ingredients The optimal ratio is still about 1: 1 (weight / weight). Surprisingly, the particles produced can be glass-milled to a large particle size distribution while still maintaining excellent properties. The processing of dry powder is very simple, and after milling Only a very small amount of non-skinned hydroxypropylmethyl 纗 vitamins were found. When made into ultra-high molecular weight hydroxypropyl methyl 绻 vitamins: a granular derivative of sucrose (1: 1 weight / weight), and milled Milled through No. 16 mesh sieve to make more than 40: 1; particles are between No. 18 and 2.5 meshes, 305: between No. 25 and 40 meshes, and about 10% of birds are below 60 No. eyes The granulated derivative exhibits excellent properties when used. The granulated derivative (such as 5 to 10 grams) can be directly dispersed in cold juice or water of 6 to 8 ounces * without relying on the assistance of the next step of the formula, it can provide a mouth with a very low viscosity increase. Grit free dispersion. The hydroxypropyl methylatedin derivative can be blended with other dry mixed powders to make a formulated product. For example, flavoring agents are usually present in the formulation. Examples of added flavoring agents are powdered fruit drinks, powdered hot beverage mixtures such as cocoa mixtures, powdered mashed juice mixtures, and the like. Such dry mixed powders are well known to those skilled in the art and have been discussed in various reference literatures listed above. In addition to the foregoing *, traditionally used additives such as preservatives, buffers, colorants, anti-caking agents, antioxidants, sunscreens, vitamins and minerals can also be used in traditional ways. Coagulant. The high-viscosity grade and water-soluble vitamins of the present invention are edible, inert, nonionic vitamins ethers. The high viscosity grade tweezers ether that can be used for edible composition is the high viscosity grade wavidin 鲢 conforms to the US Pharmacopoeia-¾ clothing iT ------ · ν (Please read the precautions on the back before (Fill in this page) This paper size is applicable to China National Building Standard (CNS) Λ4 specifications (21CU297 mm-15 419375 A7 B7 V. Description of the invention (13 Specifications and (usp) printed by the Consumer Cooperatives of the Central Procurement Bureau of the Ministry of Economic Affairs and : (Υ's big bet in non-ruminant lotus milk is anti-bacterial eye-catching effect * so it will not cause gas generation due to the drunken effect, which is essentially inert and cannot be digested to the decomposition of enzymes that can be found * (3) Does not cause allergic reactions unique to some plants, and (4) is extremely disturbing for the absorption of trace dietary nutrients. Therefore, this ultra-high molecular weight hydroxypropyl methylcellulose and the above reference The follow-up vitamins are different_different • Large laxative composition as described in EP-B-0 119 479, due to the hydroxypropylmethyl paclitaxel content per dose, high molecular weight and specificity of the present invention Hydroxypropyl methyl hydrazine viscosity, and hydroxypropyl methyl ore used Example size distribution of primes. The follow-up primes used in the present invention can be prepared by known methods. US-A-3,342,805; US-A-3,388,082; US-A-3,709,876 5 US-A-4,477,657; US-A -4,410,693; and US-A-4,820,813, the contents of which are incorporated herein by reference. In general, a specific vitamine ether is prepared by the addition of sodium oxide to sodium vitamins to form basic cellulose The ft-streptavidin is then reacted with a suitable alkylating agent. After that, the scopolamine »product is purified, dried, and mined. US-A-4,820,813 teaches the preparation of high-molecular-weight scopolamine_ * which is in For example, high-speed air blows and crushes under a slight mechanical impact of an impact mill (such as an Alpine mill). This mild impact method is a cutting or dicing method that reduces particle size, which maintains molecular weight and therefore viscosity. _The method of measuring viscosity will affect the results obtained because the ionomer solution is thinned and sheared by the vitamine ether solution. Therefore, the viscosity value depends on the method. For example, W rotary viscosity agent holds a hydroxypropyl methyl ester at a low speed. Viscosity of the solution of givinine, which is 106,000 cP ( 0.5 rp », ---.------ i ------ IT ------ ^ (谙 Please read the notes on the back before filling this page) This paper size is applicable to Chinese national standards · (CN'S) A4 specifications Ø 210X29 ·? Mm 16 419375 A7 B7 V. Description of the invention (14 Printed with 1sec-1 printed by the Bayer Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs) ί But when the viscosity is measured according to the US Pharmacopoeia method At that time, it measured the viscosity of the U solution using a Uberloh capillary capillary viscometer to a concentration of 25 :, the viscosity value was 420,000 cP. From other experiments, it has been known that hydroxypropylmethyl oryzanol milled with an Alpine mill using a 2.0 aa sieve provides an aqueous dispersion that exhibits a gritty taste and / or chi stool. Therefore, improper particle size makes improperly milled hydroxypropylmethyl hydrazine unsuitable for use in the present invention. In general, the hydroxypropylmethylgavevin milled by an Alpine mill using a 2.0 µ sieve does not provide suitable pharmaceutically active constituents or fluff. The reason is that the particle size distribution of this product contains a lot of (> 5: S) fluff particles greater than 600 * 1 · (No. 30 eyes), and the fluff particles make the liquid particles prepared from the formula product containing the fluff I want the float to feel grit. Therefore, the palatability of the product is poor. The fluff particles are too large to make the dry powder mixture of the formulation homogeneous, because the fluff particles tend to segregate the dry powder mixture. Similarly * For the purpose of the present invention, hydroxypropylmethyl vinvin (> 10,00 (kP viscosity grade)), which is finely milled to fine powder as is generally known in the art, is not suitable for use as a medicine Speech composition. These traditional ball-milled hydroxypropylmethyl vegan particles have an average particle size of less than 180ua (80 mesh). This type of powder is suspended in the liquid prepared by it. Foam or foaming in the liquid *. The hydroxypropylmethyl carbamidine powder particles are easy to form a dry center because of their poor wetting properties. Its very high surface area and rapid dissolution result in a rapid increase in cobalt. This rapid (< 3 points transmutation) ---- „--- Attack ------ 1T ------ ^ ( Please read the notes on the back before filling out this page) This paper size applies to Chinese National Standards (CNS) A # Specifications ί UOX29: · Public stamps

419375 A7 ___B7_V. The viscosity of the invention (15) increases, which quickly makes the dispersion gelatinous and unsuitable or unpalatable. Iron vitamin K used in the present invention must be soluble in water. As used in 眈, “卽 刻 soluble in water” refers to 2 grams of powdered or milled wrinkled vitamins of the present invention _ can be dared to have a temperature between ου and loot; After complete hydration, a substantially clear solution or dispersion (i) is provided when the temperature of the dispersion is 20 °. The unique property of the formulated product of the present invention is that it can be directly dispersed in cold liquids at a temperature lower than the range of hydroxypropyl methyl irrigin thermal gel (50-70 t). Another characteristic of the formula product of the present invention is that it can be directly dispersed in cold water or other M water-based systems by using only a simple spoon to stir, and it can be a delicious product for human consumption. According to the particle size distribution of the fluff and / or granular derivatives determined herein, it is not necessary to rely on the use of hot liquids or off-shear stirring devices to obtain hydroxypropyl methyl vetilin pharmacologically active ingredients that are delicious, Non-sticky, non-gummy dispersion. For comparison, the second to third grams of ultra-high molecular weight hydroxypropylmethyl fervidin is injected into one of the human teeth. The method used is to blend hydroxypropylmethyl genivitamin fluff and about 15 grams of thorium-free heat. The chocolate drink mixture is then mixed into 250 ml of hot water (800) to form a hot drink. In fact, the preparation of the drink goes smoothly. The water temperature is far from hydroxypropylmethylavidin 50 -70 t: the temperature of the thermogel, so hydroxypropylmethyldivitamin is only dispersed in the hot liquid without sensible hydration or dissolution. However, when the beverage is cooled, hydroxypropylmethyldivitamin The hydration and dissolving effect of the element is opened. When the beverage is cooled to the upper limit of human body heat (ie about 50 1C ^ clothing 1T ^ (read the precautions on the back before filling in this page) This paper size applies to China's 1 standard (CNS) A4 Specification U! 0X29? Millimeter Central Bureau of Standards, Ministry of Economic Affairs, Employees' Cooperatives, Cooperative Printing 419375 A7 ________B7_ V. Description of the Invention (16)), the hydroxypropylmethyl paclitaxel gelled in the beverage to form a very orderly A single, slippery slime that people hate The formula product containing the hydroxypropyl methyl hydrazone of the present invention can be prepared by gently stirring the mixture of the fluff or granular derivatives and other dry powder formulations, and any suitable dry powder can be used for blending. Combine with instruments (such as ribbons, double picture cones, etc.) or by using ordinary kitchen supplies or manual devices to mix or shake the eaves. Do not add in this product (unless seasoning or box for such purposes) or need fat or oil. By using coarser hydroxypropyl methyl androsin fluff * such as obtained by milling through a 0.4 η sieve of an Alpine mill, it has a cellulose ratio greater than Methtlel m (commercially available from Dow Chemical Co.) cellulose The traditional fine powder form of K has a slow dissolution rate. As mentioned above, a suitable dispersion can be obtained even without using a skin-imparting agent * such as sucrose or maltodextrin. The following figure illustrates the method for preparing the composition of the present invention. Please read the notes on the back before filling this page.) This paper is fully applicable to China National Standards (CNS) compliance: 2 丨 〇: < 297 mm) -19-419375 A7 B7 V. Description of the invention ( 17 Methodology (Super High molecular weight) hydroxypropyl methyl cellulose

Alpine honing machine passed through a 0.4mm sieve or similar method to obtain the desired particle size distribution ultra-high molecular weight hydroxypropyl methylcellulose fluff or pharmaceutically active ingredient a) to coat the aqueous solution of the outer skin agent, and then B) Dry and dry at about 120 ° C and mix it with the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs to print ultra-high molecular weight formula products that are endowed with skin

--- ~ ---_---, install ------ order ------ ice (please read the precautions on the back before filling this page) This paper size applies to Chinese National Standard (CNS) A4 Specification (2 丨 〇ΧZOπ 公 庆) 20 Consumption Cooperation of Employees of the Central Bureau of Standards, Ministry of Economic Affairs, Du Printing 419375 at ___B7 V. Description of the Invention (18) The composition of the invention, especially the ultra-high molecular weight described in the third example A granular derivative of hydroxypropyl methyl hydrazone, which provides very easy dispersion and excellent organic sensory properties in water and aqueous liquids. * It will be mixed with satisfactory dispersion and hydration. Minimize the stirring time required. Going Further "The older adult prolongs the time for excessive viscosity to increase. This is particularly important when larger doses of children containing ultra-high molecular weight hydroxypropylmethylammonium are therapeutically beneficial or desirable. The composition of the present invention can be dispersed into a large amount of aqueous liquid, such as juice, water nectar and extracts (such as apples, oranges and apricots). This composition is also well blended with other formula dry blend powders (such as Tang ™ brand orange drink blends, SlinPast ™ and Hollick) that require K water or milk to be infused. The composition is also engraved and dispersed in apple clams, coagulated dry pudding mixture and cassava powder, dried food dried mixtures (such as dried glutinous rice cakes and muffins), granola rod-shaped compositions, etc.

Schultz's patent (US-A-4,820,813, the content of which is incorporated herein by reference) discloses a process involving the preparation of a fine powder containing ultra-high molecular weight hydroxypropylmethyl levulinin by low-impact milling containing ultra-high molecular weight hydroxypropyl acrylic acid. Method for methyl methyl levanosine. Although this method can be used to produce the fluff of the present invention, it does not do so. An example of the size of the hydroxypropylmethyl fluorenin produced is that the size is less than 80 silk eyes. The purpose is to obtain a very small example size M that mimics a known methyltonin product while maintaining high viscosity. The composition of the present invention has a super polymer fi hydroxypropylmethyl stigmatonin, which can reduce serum sterol by M. In order to achieve this result, the active ingredient (ultra-high molecular weight hydroxypropyl methyl vitlavin) should be approximately 1 to 8 per dose. This paper size is applicable to China National Standard (CNS) Λ4 specification (2 丨 〇 乂) 29? Mm) ----------- wei ------ ΐτ ------ ^ (Please read the notes on the back before filling this page) Workers' Cooperative Cooperative Printing 419375 A7 _B7_ V. Description of the invention (19) The port of grams is present in the formula, preferably about 2.5 to 5 grams per dose. The number of doses administered per day will depend on the degree of reduction required for that particular patient. Generally speaking, doses of about 2 to 3 锢 each contain about 1 to 8 grams. Therefore, about 2 to 25 grams are administered daily in divided doses. While not wishing to be bound by theory, the pip point of the hydroxypropylmethyl levulinin composition of the present invention and the results obtained from its use are considered to be due to its specific particle size distribution and large Molecular weight, especially for ultra-high molecular weight hydroxypropylmethylpanearin, 分子量 its molecular weight, viscosity grade and dispersibility. Any method that contributes to the size distribution and molecular weight of the hydroxypropylmethyl levulinin particles is within the scope of the present invention. The present invention will be made clearer by considering the following example, which is only used as an example for the present invention. 2.5 grams of flute 1 mill milled through a 0.4miD sieve on an Alpine mill. The ultra-high molecular weight hydroxypropyl methyl hydrazine fluff was neutralized in a 10 ounce (0z) plastic cup with 2 flat tablespoons ( 30.8g) of Tang ™ Brand Dry Powder Orange Drink Blend. The blend was mixed with a tablespoon only. A homogeneous withdrawal / dispersion dispersion was obtained in the form of an orange, dry powder mixture. 8 ounces (224 grams) of cold tap water (approximately 15TC) was added to the dry powder mixture once, and the spoon was stirred for 1 minute with a shovel. At the end of the stirring, a cold, smooth, palatable, muddy structured orange drink composition was obtained.规 Mix with the viscosity of the dispersion formed by the drop test, and drink the orange drink in 30-minute intervals. The orange drink is still delicious, completely delicious, and does not contain any objectionable thick strands. The paper size of the central dry paper is applicable to the Chinese National Standard (CNS) Α4 standard (210 ×;: 1; 1 ·? Public, f)- --------- i ------, 1T ------ 4 (Please read the notes on the back before filling out this page) 22 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 419375 A7 __B7 V. Description of the invention (20) Dry clumps, or any other objectionable granular substance. It is painlessly heated to a temperature higher than the thermal gelatinization temperature of ultra-high molecular weight hydroxypropylmethyl oryzanol, and a composition of 2.5 g of ultra-high molecular weight hydroxypropyl methylandrogen is formed in the form of a liquid mash formula. The second milled 5.1 g of ultra-high molecular weight hydroxypropylmethyl tweezers vitamin fluff as described in the first example and a 2 ounces (28.6 g) Tang dried powdered orange drink in a 10 oz plastic cup The blend is mixed. The blend was stirred only with a spoon. A homogeneous cut / dropped dispersion was obtained in the form of an orange, dry powder mixture. 225 grams of cold tap water (approximately 13 F) were added to the dry powder mixture in one portion, and stirred with M tablespoon. After 30 seconds of constant stirring, a homogeneous suspension with apricot kernel nectar structure was obtained. The suspension is delicious and free of any dried particles. Hold the embroidery and stir, and about 60 seconds after adding water, still keep a completely delicious orange drink blend. At 120 seconds, thickening occurred further. At 180 seconds, it will open and form a soft gel that can be picked up with a spoon and has a fruit structure. At 210 seconds, a soft gel with apple sauce viscosity was obtained. If the formula needs to be consumed at this later stage, replace the orange flavor with an apple flavor. It is not necessary to rely on heating the liquid to a temperature higher than the thermal gelatinization point of hydroxypropyl methyl hydrazine, so as to achieve a composition having 5.1 g of ultra-high molecular weight hydroxy propyl methyl gadovin in a completely liquid form. Plug 3 cases of box formed by 1 weight part of M sugar in 1 weight part of water ^ 衣 1Τ ------ ίν.- (Please read the precautions on the back before filling in this tile) This paper · Dimensions are applicable to national standards (CNS) Λ4 gauge Luo + 2! 0 × 291 mm; 23 419375 A7 B7 printed by the Consumer Cooperatives of the Central Government Bureau of the Ministry of Economic Affairs 5. Description of the invention (21) Hot water solution (above 50 Ii) Wet granulate 1 part by weight of ultra-high molecular weight hydroxypropylmethyl fervidin fluff, and prepare M sucrose. Ultra-high-molecular-weight hydroxypropylmethylneuvidin (marsh sugar; ultra high) The molecular weight hydroxypropylmethylarsonin is a 1: 1 weight / weight) granular derivative. A wet, brittle material was obtained. The material was dried at about 120 to constant weight. The dried granules * that are then milled and sieved pass about 953: or more through a 1.0 ·· sieve (U.S.A. No. 18). The dry particle derivative contains less than IX weight / weight of residual moisture. The precipitated bulk density of the dried particles was about 0.43 g / cc. The dry particle derivative is attractive in appearance and can flow freely. The low-dust particle gives the dry particle derivative excellent powder rolling and holding power of M g. The 1: 1M hallose-supplying extra-high molecular weight hydroxypropylmethylmineretin fluff of the outer skin is used to prepare a multi-dose formulation of each tincture. For example, the dry granular derivative can be immediately dispersed in a variety of liquid fruit juices and beverages, such as fruit juices, water-containing nectar, and extracts (such as apples, oranges, and apricots). It is smoothly dispersed in apple clams and blends well with the formula's dry blended powders (such as Tang ™ brand orange drink blends, SlimPast ™ and Holic, such as those brewed with water or milk), which can be engraved for direct addition to Various baked food recipes, coagulated dry pudding mixes, baked food dry mixes (such as ravioli and muffins), and granola bar compositions. Step 4: Use maltodextrin instead of sucrose as the coating agent, and repeat the coating step of Example 3. The sugar-free granule derivative is obtained, which is suitable! I nn HI. Packing — II i I ^ ll I n I I'v (Please read the precautions on the back before filling this page) This paper is suitable for Chinese national standards · (CNS) A4 specification (: 10X 29mm-24 419375 Α7 Β7 Printed by the Consumer Cooperative of the Shenyang Bureau of Standards, Ministry of Economic Affairs. 5. Description of the invention (22 as a formula product or blended with other dry powder ingredients) Other formulated products. Fili Sample A: 2.53 grams of ultra-high molecular weight hydroxypropylmethyl zetavin (400,00 GcP viscosity grade) and 30.8 grams of 3 ^ " brand dry powder passed through a 2.0an sieve Orange drink mix. Mix 15.5 grams of the formula in a 9 oz plastic cup and a plastic spoon. Stir. It is difficult to mix and a uniform dry powder is not obtained. Cellulose easily binds together to form a barley-like sugar. Add 8 ounces of cold water to the dry mixture at once and stir with a spoon. Many bubbles form in the matrix and the liquid on top is like foam. Stir with dragon 1 minute. Many Coarse strands appear on the sides of cups and spoons. About 2 tablespoons of the mixture are gravelly and granular, while the moist but fully hydrated particles of the macromolecular hydroxypropyl methyl hydrazine are obvious. Sample B: 2.50 grams of ultra-high molecular weight hydroxypropylmethyl androstrin (400, OOOcP viscosity grade) milled through a 0.4aa sieve as in the first example, and 25.2 grams of Tans' " brand dried powder orange drink are mixed Place the powder in a 9 oz plastic cup and mix with a plastic spoon. This powder is easy to mix with a spoon of M polymer and agglomerates of polymer S hydroxypropylmethyl fiber. Unbundle on the spoon and mix and disperse it into the Tans ™ brand orange drink. Mix. Add 8 ounces of cold water (about 10TC >-) to the resulting homogeneous formula product, stir with M tablespoon. After mixing for 1 minute, the liquid shows some foam, and then continue to There are some rough irrigation points, and the paper size of the paper applies the Chinese National Standard (CNS) AJ specifications (Gonglong. Binding ^ (Please read the precautions on the back before filling this page) -25 419375 A7 B7 Central Ministry of Economic Affairs Printed by the Bureau's Consumer Cooperatives 23 There is no granular taste. Many bubbles are formed in the matrix and the liquid on the top is like foam. Stir for 1 minute. Viscosity increases slowly. Mainly. Before the viscosity is further increased * the compound is still completely acceptable within at least 5 minutes. Sample C: 2-5 g of traditional fine powder hydroxypropyl methylarsin (80,000 cP Viscosity grade, > 80X less than 80 mesh) and 25.2 grams of > ^ | ^ —brand dry powder orange drink mix in a 9 oz plastic cup. 8 ounces of cold water (about οου) was added to the resulting uniform powder mixture (formulation product), and the mixture was mixed with M tablespoon. After 1 minute of stirring, the liquid showed many foams and many air bubbles in suspension. The tasting test showed no granular feeling in the mouth at 1 minute, but the viscosity increased quickly. Within 3 minutes, the mixture became too sticky to drink. Sample D: 5.2 g of ultra-high molecular weight hydroxypropylmethylfervidin villi (420,00〇cP) coarsely milled through a curtain to give an outer skin (1: 1 weight / weight S) through a 16-mesh sieve Viscosity grade) and 25.2 grams of Ungw brand dry powder orange drink blend in a 9 oz plastic cup. The M powder easily blends the two powders. The resulting powder mixture was non-uniform and apparently had some large white particles on an orange background. 8 ounces of cold water (about 10 ° C) was added to the formula product * Stir the mixture with a spoon. No foam or rough dimension formed. This Liquid Skull Suspension resembles a Tang ™ brand beverage with suspended pulp. At 1 minute, the palate is specifically removed from the flesh in Tang ™ drinks. At 3 minutes, the suspension showed a very low viscosity increase. This paper size applies the Chinese National Standard (CNS) A4 gauge; Z10X 297 mm) 26 ----: --r ----- pack- ----- Order ------- ^ (Please read the notes on the back before filling out this page) 419375 A7 B7 V. Description of the invention (24) Consumption cooperation by employees of the Central Standards Bureau of the Ministry of Economic Affairs Gummy. At 5 minutes, the suspension was still non-sticky, and the floating pulp-like particles were very soft. At 7 minutes, there was no noticeable difference in taste. At 12 minutes, the pulp-like particles are very gioppy and the viscosity begins to increase. Sample ε: 5.1 g of coarsely ground ultra-high molecular weight hydroxyl group with sucrose and a rind (1: 1 weight / weight) passed through a 16 mesh sieve The propylmethyl vilizolin fluff (420, OOOcP viscosity grade, such as milled in the first case) was placed in a 9 oz plastic cup without other added ingredients. 8 ounces of cold water (about 10 C) was added to the powder in one portion, and the mixture was stirred with M tablespoon. No foam or thick strands formed. At 1 minute * the suspension included transparent gel particles in water. No foam or opaque gel particles (fisheye> exist. The stable, easy-flowing aqueous suspension is maintained for at least 10 minutes. At 13 minutes, the suspension has a mucus-like viscosity. At 25 minutes, it forms Soft, flowing gel. Sample P: When sample E was poured into human water by pouring 5.0 g of ultra-high molecular weight hydroxypropylmethyl fulvidin granular derivative into the skin > A similar test was obtained The result of sample E. This shows the variability of the granular derivate of the ultra-high molecular child hydroxypropylmethyldivitamin, which is endowed with 1: 1 sucrose, as a formula product in 6 cases. The ultra-high molecular child hydroxypropylmethyl azimonin granular derivative, sample E and sample F, which are applied to the outer skin, found that the composition is very -----: ---- loading ----- -Order ------ Dream (please read the precautions on the back before filling out this page) This paper size applies Chinese National Standard (CNS) Α4 gauge (; 0X29? Mm 27-419375 V. Invention Explanation (25) A7 B7 is suitable for further inclusion in the final product, and itself as a final product. It is important that Granulated derivatives or formulated products can be simply mixed with a spoon, that is, they can be dispersed into cold water (0-20C) or warm water or heated beverages (40-50Ό). Under these conditions, the viscosity increases slowly, and avoids Gritty. The particle size of the granular derivative is very large. The particle size distribution of the granular derivative is between about 752 and larger than the 40th pore (420wb) but less than the 16th mesh (1200 / ζ «), and less At about 10X less than 80 mesh (180μ · >. However, when the skin-derived ultra-high molecular weight hydroxypropylmethyl hydrazine derivative is dispersed in water, it quickly forms a separate gel and its Mouth feels like soft flesh particles. The suspension of the gel maintains an acceptable viscosity for at least 4 minutes (2.5 g of ultra-high molecular weight hydroxypropylmethyl levulinin equivalent; 8 oz. Dispersion). Example 7 Stir 5.9 grams of sucrose into the outer skin (1: 1 w / w) of ultra-high molecular weight hydroxypropylmethyl glutenin (420,000 cP viscosity grade as described in Example 6) into 4 oz. Cold (10t) at a time Applesauce. Get a completely delicious applesauce suspension of this granular derivative .The viscosity, taste, and structure of applesauce suspension remain stable and attractive for at least 15 minutes ----.-- ^ --- i ------ ΪΤ ------- ^ (Please read the precautions on the back before filling this page) The 8th case printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs will be 5,0 g of ultra-high molecular children's hydroxypropylmethyl vilomycin fluff (420,000 cP viscosity Grade, such as 1 case of milling) In a 10 ounce cup, join with 10.0 grams of JELL-0 " * brand sugar-free ready-to-eat chocolate bar dry powder pudding mixture. The produced formula product is a uniform dry brown powder paper. The standard is applicable to the Chinese National Standard (CMS) M specifications (210X297 mm) 28 419375 A7 B7 26 V. Description of the invention (final mixture. Add 6 ounces at a time to the powder mixture (178g) cold (12Π) milk fat milk. Stir the mixture with a spoon for 2 minutes. The thick, smooth pudding obtained has excellent taste and flavor. Considering the specifications and implementation disclosed herein, the Other embodiments are clear to those skilled in the art. The specifications and examples are only intended as examples, and the actual scope and spirit of the present invention are defined by the scope of the following patent applications. --- ^ --.--- -Installation ------ Order ------- (Please read the precautions on the back before filling out this page) Printed on paper, printed in Chinese by the Central Building Standard Bureau of the Ministry of Economic Affairs Quasi (CNS Μ4 specification f not) 29 ^ OQ-

Claims (1)

Printed by the Consumers' Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs Λδ B8 C8 D8 VI. Application for Patent Range No. 86100432 Material Requisitions Request Revisions for the Material Revisions I Date of Revision: 41JIJ9 in 88 A powdered hydroxypropyl methylcellulose composition in which there is an skin-coating agent that coats the hydroxypropyl methylcellulose, and the hydroxypropyl methylcellulose has: (a) — the particle size distribution has Less than or equal to 5% of the hydroxypropyl methyl cellulose particles is greater than the upper limit of about 600 times w and less than or equal to 50% of the hydroxypropyl methyl cellulose particles is less than the lower limit of about 180; and (b ) —Viscosity in a solution of 2% by weight of water at 20 ° C is greater than 10,000 to 2,000,00,00cp cp 2. The composition of item 1 in the scope of patent application 'wherein the hydroxypropyl group The viscosity of fluorenyl cellulose is greater than about 25,000 to about 2,000,000 cp. 3. The composition according to item 1 of the scope of patent application, wherein the viscosity of the propylpropylfluorenyl cellulose is greater than about 50,000 to about 800,000 cp. 4. As for the composition in the scope of the patent application, the viscosity of the hydroxypropylmethyl cellulose is greater than about 200,000 to about 50,000, cp. 5. The composition according to item 1 of the scope of patent application, which further includes a flavoring agent. 6. The composition according to item 1 of the scope of patent application, further comprising one or more selected from preservatives, buffers, Additives for colorants, anti-caking agents, antioxidants, sunscreens, vitamins, minerals and coagulants. 7 · The composition according to item 1 of the scope of the patent application, wherein the ratio of the ingredient to the outer skin agent relative to the hydroxypropyl methylcellulose is about 0.5: 1 to about ---------- --- Installation -------- --Order ------ Green (Please read the notes on the back before filling this page) 193 A8 BS CS D8 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Application scope of patent 2.1 (w / w) 〇8 'If the composition of scope 7 of the patent scope is claimed, it further includes one or more selected from preservatives, buffers, colorants, anti-caking agents' Anti-aliasing agents, sunscreens, vitamins, minerals and coagulants. 9- The composition according to item 1 of the scope of patent application, wherein the skin-coating agent is a natural sugar. 10 > The composition according to item 9 of the scope of patent application, wherein the natural sugar is sucrose. 11. The composition according to item 9 of the scope of patent application, wherein the injury to the outer skin group is maltodextrin. 12. The composition according to item ^ of the application, wherein the ratio of sucrose to hydroxypropylfluorenyl cellulose is from about 0.25: 5 to about 4: 1 (w / w). 13. As for the composition in the scope of application for item π, the ratio of ninge bran to hydroxypropylmethyl cellulose is about 0.5: 1 to about 3: 1 (w / w). 14. The composition of item η in the scope of patent application, wherein the ratio of sucrose to hydroxypropylmethyl cellulose is from about 0.75: 1 to about 2: l (w / w) »15. The composition of item 11 wherein the ratio of sucrose to hydroxypropylfluorenyl cellulose is about 1: 1 (w / w). 16.-A pharmaceutical composition for reducing the serum cholesterol of non-ruminant mammals in need of treatment, comprising a composition in the range of about 1 to about 8 grams per dose of the composition as claimed in claim 1 of the patent application. 17.-A pharmaceutical composition for reducing the serum cholesterol of a non-anti-mammalian mammal in need of treatment ', which comprises the composition as claimed in item 7 of the patent application in a dosage form of about 1 to about 8 grams per dose. -2- This paper A degree is applicable to China National Standards (CNS) A4 grid (210 × 297 mm) -------- 丨 Installation ------ Order ------ \ (Please first (Please read the notes on the back of this page and fill in this page again.) Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumer Consumption Cooperative, Λδ Β8 C8 D8 VI. Application for Patent Range 86100432 1. A kind of dry mixed powder hydroxypropyl methylcellulose composition dispersible in cold water, wherein there is a coating agent for coating the hydroxypropyl methylcellulose, and the hydroxypropyl methyl cellulose Has: (a)-The particle size distribution is an upper limit of having less than or equal to 5% of hydroxypropylmethylcellulose particles greater than about 600 times w and having less than or equal to 50% of hydroxypropylmethylcellulose particles Less than about 180 must be the lower limit; and (b)-the viscosity is greater than 10,000 to 2,00,00,00 cp in a solution of 2% by weight of water at 20 ° C; The composition of item 1, wherein the viscosity of the hydroxypropylfluorenyl cellulose is greater than about 25,000 to about 2, Took office, 〇〇〇 cp. 3. The composition according to item 1 of the scope of patent application, wherein the viscosity of the propylpropylfluorenyl cellulose is greater than about 50,000 to about 800,000 cp. 4. As for the composition in the scope of the patent application, the viscosity of the hydroxypropylmethyl cellulose is greater than about 200,000 to about 50,000, cp. 5. The composition according to item 1 of the scope of patent application, which further includes a flavoring agent. 6. The composition according to item 1 of the scope of patent application, further comprising one or more selected from preservatives, buffers, Additives for colorants, anti-caking agents, antioxidants, sunscreens, vitamins, minerals and coagulants. 7 · The composition according to item 1 of the scope of the patent application, wherein the ratio of the ingredient to the outer skin agent relative to the hydroxypropyl methylcellulose is about 0.5: 1 to about ---------- --- install --------order ------ green (please read the precautions on the back before filling this page)