TW201039832A - Use of lanostane and Poria extract in treating cachexia - Google Patents

Abstract

A pharmaceutical composition for treating cachexia, and in particular for treating cancer cachexia. The composition contains a lanostane compound as a potent component. A suitable source of the lanostane compound is a Poria extract from metabolite, sclerotium, or fermentation product of Poria cocos (Schw) Wolf. The Poria extract contains 1-60% of the lanostane compounds by weight of the extract, and is devoid of secolanostane.

Description

[Technical Field] The present invention relates to a pharmaceutical composition for preventing and treating a cachexia (such as cachexia and anorexia), particularly a cachexia caused by cancer. The pharmaceutical composition of the present invention contains a lanosterol compound as an active ingredient. A suitable source of this lanosterol compound is the hydrazine extract. In addition, Cordyceps sinensis, Antrodia camphorata and Ganoderma lucidum are also sources of possible sterol compounds. Ο [Prior Art] Cachexia indicates that it is in a bad state of weakness, often caused by diseases that cause anorexia and endocrine and immune system changes, fatigue, muscle and visceral protein reduction, and ultimately weight loss. • Cachexia is a common symptom in chronic or critically ill patients. About 70% of patients with cancer and pancreatic cancer have such symptoms. At the end of the cancer, about 80% of patients with Q have symptoms of cachexia, which is characterized by the fact that even if the patient increases the amount of food intake or increases the intake of nutrients, it will not prevent or prevent the patient's weight. The continued decline. In the treatment, hormone appetite is often used to promote Qi J (such as Megestrol, medr0Xypr0gester0ne acetate), but in fact some people think that it is suspended weight gain (only water and fat increase), body muscle mass does not increase, activity ability, physical fitness is not See improvement. Conversely, some side effects such as blood clots, edema, hemorrhage, high blood sugar, and high blood pressure can occur. Catabolic consumption or cachexia is a feature that is not 3 201039832 Autonomous progressive consumption of fat and skeletal muscle, refractory weight loss to increase nutrient input, increase in static energy expenditure (REE), decreased protein synthesis, changes in carbohydrate metabolism (Cari cycle activity increases), ATp-ubiquitin-dependent ubiquitination of muscle-dissolved protein pathways, and syndromes of excessive catabolism of fat tissue through fat dissolution (Body JJ, Curr Opin 〇nc〇i η : 255 __ 60, 1999, Muscaritoli M, et al : Eur J Cancer 42 : 31-

41, 2006). Usually, the patient is diagnosed with cachexia after the patient has been relieved by at least 5% or before the rickets. About half of all cancer patients experience some degree of catabolic consumption, and higher incidences are seen in cases of lung, sputum, and gastrointestinal malignancies (Dewys WD, et a丨: Am j MM 69 : A) ~ 7, 1980). The syndrome can also be found in patients with impaired diseases such as spleen and in patients suffering from bacterial and parasitic diseases, rheumatoid arthritis and chronic diseases of the intestines, liver, kidney, lungs and heart. Cachexia is also associated with anorexia, which can be caused by aging or by physical injury and burns. Cachexia syndrome reduces the patient's functional ability and quality of life, worsening the underlying condition and reducing tolerance to drugs. The degree is inversely proportional to the patient's survival time. It usually represents a poor prognosis. In recent years, the disease and disability associated with dilatation have become the main health concern and importance. Anorexia (10) is a medical term for loss of appetite) The performance 'can be seen in cancer, infectious diseases, chronic organ failure and traumatic patients. Anorexia is a serious syndrome because it causes Calorie Reduced and malnourished. The performance of anorexia includes a decrease in taste and smell of food, early satiety, decreased hunger and even total aversion to food. '4 201039832 Symptoms of nausea and ° vomiting. Little is known about the cause of anorexia. However, effective treatment is limited. Some studies indicate that hormones, social and psychological factors may be an important factor in the occurrence and progression of this syndrome.

', 'In fact, the disease is often associated with cancer, but it has not been confirmed that the occurrence of cachexia has a relationship with the size of the tumor, the stage of the disease, and the type or period of the malignant disease. However, @‘ cancer cachexia is often associated with decreased calorie intake, increased static energy expenditure, and protein, fat, and carbohydrate metabolism. For example, some of the most important changes in carbohydrate metabolism include an increase in the conversion rate of glucose, a rise in liver glycogen, an increase in glucose intolerance, and an increase in blood sugar. Increased fat solubilization, increased conversion of free fatty acids and glycerol, hyperlipidemia, and lipoprotein lipase activity are also frequently observed. It is important that the weight loss associated with cancer cachexia is not only due to reduced body fat storage, but also to the reduction in total body protein mass and extensive skeletal muscle consumption. Increased protein turnover and poor regulation of amino acid oxidation may also be important factors in the deterioration of this syndrome. In addition, in response to specific host-derived factors of cancer, such as 'pre-inflammatory cytokines (tumor necrosis factor i (TNF-a), interleukin-1, interleukin-6, and 丫-interferon), acute phase Proteins, such as sputum reactive proteins, and specific prostaglandins also appear to be associated with cancer cachexia. In traditional Chinese medicine, it is recommended that the elderly should be given Chinese medicine every day. In addition to being prone to illness, the elderly can help to delay aging and live longer. The applicant of the present invention discloses a pharmaceutical composition for enhancing human immunity by using EP 1535619 A1. The composition contains erostane compound as an active ingredient, can enhance immunity and is used for virus infection prevention 201039832 And treatment. On the other hand, Aloe vera extract and its purified (lanostanes) can suppress immunity and are used for the prevention and treatment of allergic (asthmatic) caused by IgE. This inhibition is disclosed in Chinese Patent No. 97123189 and PCT/CN2008/001218. case. From these two patent applications it is shown that sputum extract and its lanostanes can modulate immunity. Applicants of the present invention have disclosed that the human intestinal cells can be enhanced by the action of lanthanum and the purified lanosterone in the Chinese patents No. 97111791 and PCT/CN2008/000749, and the glucose and amine groups are enhanced. Acids, vitamins (folic acid) Therefore, we believe that the extract of the extract, especially the lanosterol compound (lan〇StaneS), may contribute to the good or the cure of the cachexia associated with nutrition and immunity. In the present invention, human lung cancer cells are transplanted into mice for experiments, and it is also clear whether the components of the stroke and the lanosterol compound can have a sputum effect on the disease, and whether the human lung cancer cell-transplanted mouse and the normal mouse are observed. - There is a normal appetite and the body weight is normal and there is no gradual reduction.

SUMMARY OF THE INVENTION The main purpose of the priming is to provide a pharmaceutical composition for the treatment of the prevention and treatment of a consuming disease (such as cachexia and anorexia), especially cancer-caused cachexia. Another purpose of the use of the first month of the present invention is to provide a sputum extract from sputum; use for the treatment of prevention and treatment of a wasting disease, such as cachexia and nausea, especially cancer caused by cachexia. The aim is to provide a new use of lanosterol (1_stane) 201039832 for the treatment of prevention and treatment of consumptive diseases (such as cachexia and anorexia), especially cancer-caused cachexia. A pharmaceutical composition for preventing and treating a wasting disease (such as a cachexia f and anorexia) in a mammal (for example, a human), comprising a wool solid having the following chemical formula (I) as an active ingredient for preventing and treating an effective amount of a wasting disease Alcohol or its medicinal salt:

Wherein Ri is Η or CH3; R2 is OCOCH3, =0 or OH; R3 is Η or OH; R4 is -C(=CH2)-C(CH3)2Ra, where Ra is H or OH, or -CH=C( CH3)-Rb, wherein Rb is CH3 or CH2OH; 115 is hydrazine or OH; and 116 is CH3 or CH2OH. Preferably, the lanosterol (I) has the following chemical formula: 7 201039832

8 201039832 HOOC,

ϋ 较佳 Preferably, the composition of the present invention contains 0160% by weight of lanosterol (I) or a pharmaceutically acceptable salt thereof. Preferably, the compositions of the invention are administered orally. A further object of the present invention is to use the extract of Lycium barbarum L. as the source of the wool sterol (1), which contains the extract! % by weight of lanosterol of the above formula (1) and substantially free of ring-opened lanosterol. Preferably, the obtained extract is prepared by a method comprising the steps of: 'extracting the metabolite of the fungus, the fermentation product of the fungus or the fungus of the fungus by one water, methanol, ethanol or a mixed solvent thereof Hyphae; b) "shrinking step a) % taking the obtained liquid; 导入 introducing the concentrate obtained in step a) into a rubber hose column; squeezing the second hose with a low polarity extracting agent (eluent) Column: and a raw eluate; and, e) concentration of the eluent of step d). Preferably, the analysis by the elution layer chromatography obtained in the step e) has a - chromatography value (Rf) ^ Q", and the material is detected by the thin moth of Shi Xibei, and the developing liquid is dichloromethane: Methanol UV Lamp and 9 201039832 Preferably, the solvent used in the extraction of step a) is 95% alcohol. Preferably, step a) comprises extracting the metabolite of the fungus, the acid fermentation product of the eucalyptus fungus or the hyphae of the sputum fungus; adding a test solution to the p Η value of 9 -11, Separating the given gamma, gamma*, ruthenium base 1' raw water solution, adding -acid to the alkaline aqueous solution to its enthalpy value of 4-7 to produce a sinking substance; separating the shovel The precipitate was extracted with alcohol and the extract liquid was separated. Preferably, the concentrate of step b) is further extracted by a volume ratio of Ο Ο (iv) V/V aqueous methanol solution and a two-phase solvent of hexane; the methanol layer is separated, and the methanol layer is condensed. Suspected AA A#*» »1 Reimbursement (4) Aberdeen (4) Retraction was used as the feed for the Shixi rubber column of step c). A preferred 'step d) low-polarity extracting agent is a mixed solvent of bismuth, "dichloromethane and methanol": the best of the extract contains 5_35 wt% of wool solids Alcohol (1) Preferably, the composition of the present invention is ligated to a nutrient such as glucose, amino acid, vitamin or a combination thereof. Preferably, the wasting disease of the present invention refers to cachexia, Preferably, the cachexia is caused by cancer such as lung cancer, stomach cancer, pancreatic cancer, rectal cancer, breast cancer, oral cancer or nasopharyngeal cancer. Preferably, the wasting disease of the present invention refers to cancer, anorexia, aging. Preferably, the pharmaceutical composition of the present invention is administered to a human in a dose of sterol (1) at a daily dose of not less than 8.4 mg. Preferably, the present invention Pharmaceutical composition - carrier or diluent. "Inclusion-Pharmaceutical Allowance 201039832 The present invention has a formula (η() of citric sterol or a pharmaceutically acceptable salt thereof, and a sputum extract as a cancer string" a treatment with severe weight loss. Guan Zhi, Zhuang, Guang ~ ^ ° Diseases in addition to cancer, there are still AIDS, aging, rheumatoid arthritis, lungs and phlegm. * 胛 ... nuclear, fibrocyst, Crohn's disease, infectious diseases, etc. caused by cachexia. Fluorescence surgery or cancer patients (with chemotherapy or radiotherapy) cause weakness and urgent need to supplement nutrients (amino acids, (tetra) sugars, vitamins) to improve. The active ingredients of the present invention can be added to milk powder, beverages, foods. As a nutritional supplement, it can also be used as a medicine, such as a tablet, a capsule, a granule, a liquid, an injection, etc., for medical purposes. [Embodiment] Caclexu means that the human body is in a weak state, causing evil. • There are many different reasons for the disease, but there is no one thing to do. Objectives: In terms of cancer, cancer cell release factors or the body's immune response to cancer cells release various factors directly or indirectly. Causes anorexia, changes in the endocrine and immune system of the body, thus reducing the body's fat and muscle protein Causes patients not to like diet, body weakness and weight loss. Diseases related to cachexia are cancer, infectious diseases (such as tuberculosis, AIDS), autoimmune diseases (rheumatoid arthritis), the elderly, fiber Cysts, Crohn's disease. In cancer patients, especially those with stomach cancer and pancreatic cancer, 'about 70% of patients will have such symptoms. In addition, at the end of cancer, no matter what kind of cancer About 80% of patients will have cachexia symptoms. If you increase your diet or other treatments by feeding or intravenous injection, you can't prevent or prevent the patient's weight from falling. Use of hormones and remedies (eg, \4egestrol, medoxy progesterone) 'But in fact some people think that it is a pause in weight gain (only water and fat increase) 'the body muscle mass has not increased, and the ability to move has not improved. Conversely, some side effects such as blood tests, edema, hemorrhage, high blood sugar, and high blood pressure can occur. A suitable method for preparing an active ingredient for treating cachexia from the present invention is, for example, the method disclosed in the aforementioned EP 1535619 A1, which comprises extracting hydrazine by a conventional extraction method to obtain a crude extract, and then passing through a chromatography method. , divided into small lan 〇 e e ( 以 以 以 以 以 以 以 以 以 以 以 以 以 以 以 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷 二氯甲烷(Secondary gas methane: methanol (9 〇: 1 〇 or ... 1 〇〇) * is the extract), wherein the thin layer chromatography of the stone-forming gel shows the location of the lanostane The chromatographic value (Rf) is 匕〇1 when the solvent is dihalomethane-methanol (96:4), and the chromatographic value is less than 0.1 for the composition of the ring-opening lanosterol O (secolanostane). The lanosterol moiety can be further separated by a ruthenium tube column stratification method in which a plurality of lanosterol (1311__) compounds are separated from the extract using a gas-burning methanol (97.3 to 95:5). The invention is further described in detail below with reference to the embodiments, but without restricting the invention. Example 1 260 liters containing 75% alcohol, heat extraction and extraction of Yunnan glutinous rice 26 kg 12 201039832 three times combined with alcohol extract, concentrated under reduced pressure to obtain 225.2 g of extract. The extract was quantitatively analyzed to obtain 76.27 mg of lanostanes per gram of extract 'K1 (Pachymic acid) 33_4 '克' Kl-1 (dehydropachymic acid) 9.59 gram, K2-1 (Tumulosic acid 19.01 2克' K2-2 (dehydrotumulosic acid) 6,75 克克, K3 (Poylporenic acid C) 5.06 mg, K4 (3-epidehydrotumulosic acid) 2_46 gram. o ^ Example 2 Example 1 Alcohol extract 125 g was extracted 6 times with 1 3 liters of methylene chloride. The combined dichloromethane extracts were concentrated to give 22.26 g of the extract. Dissolve the dichloromethane extract with 95% hot alcohol, filter and dissolve in the cold. The filtrate is added with a small amount of water until the alcohol content is 45%. At this time, a precipitate will be formed, and the precipitate will be obtained by centrifugation.丨 7.4 g of precipitate. Quantitative analysis showed that each gram of precipitate contained 264.78 mg of lanosterol ◎ Uanostanes), of which 159.7 mg of pachymic acid, 56.96 mg of dehydropachymic acid, and K2-1 (Tumulosic acid) 24· 43 mg, K2-2 (dehydrotumulosic acid) 8.8 mg, K3 (polyporenic acid) 9.84 3-epidehydrotumulosic acid 5.05 mg. The precipitate was examined by Shihua gum thin layer chromatography to prove that it did not contain ring-opened lanosterol. Example 3 100 kg of medlar tea was boiled in 800 kg of water for 3 hours, left to stand 13 201039832, cooled to 50 C, the solution was adjusted to pH n with 5N Na〇H, and stirred for 3 hours. Next, the liquid and the solid were separated by a centrifuge, and the solid was further added with 8 (10) kg of water. The mixture was adjusted to ΡΗ with NaOH as described above, stirred and centrifuged to remove the solid. The two liquids were combined, and the liquid was vacuum-concentrated to 1 〇〇 kg of solution at 50 Torr, and then 3N HCl was added to pH 6.5 to produce a precipitate. The precipitate was separated and washed with 40 L of H20, followed by centrifugation to separate the precipitates. Add 8 L of water to spray dry to obtain about 380 g ^; The powder was extracted three times, and the extract was combined and centrifuged to obtain 238-9 g of an alcohol extract. The extract was subjected to silica gel thin layer chromatography (TLC) to detect that it did not contain ring-opened lanosterol. The extract is further subjected to HPLC cleavage. The main component is K2 214 mg, K3 23 mg 'K4 24 mg and a small amount of K1 4.52 mg per gram of the extract, ie the extract contains about 265 mg of lanosterol per gram (lan) 〇stanes). • Or extract the powder with 4 L of 50 ° / ° alcohol solution, remove 50% of the alcohol solution and collect the insoluble powder. Repeat three times to obtain 245.7 g of 〇 5〇% alcohol solution insoluble matter, which is detected by TLC method. The insoluble matter does not contain ring-opened lanosterol, and the insoluble matter is separated by HPLC purification. The main component is K2 214 mg, K3 23 mg, K4 24 mg and a small amount of mg per gram, that is, about 261 mg per gram. Lanostanes ° Example 4: 30 kg of glutinous rice in Yunnan, ground into powder, extracted with ι2 〇 [alcohol (concentration 95 /.) for 24 hours, and separated by filtration. Repeat the above extraction and solid 14 201039832 liquid separation three: owed. Combine (4) and concentrate it to obtain 2 (1) grams of extract. The dry extract was subjected to partition extraction by a two-phase extractant (hexane: 95% methanol: 1). The methanol layer was taken out and concentrated to give 246.9 g of dry solid. The dried solid was separated by a Shih Hose column, which was filled with the dry solid weight 1 (), a time-glued gel, and was constructed from Merck, Silica (10) 6 〇, 7 〇 23 23 (10). With dichloro τ...

The methanol mixture is used as a ehient, and is sequentially extracted in a ratio of 96:4, 9g:ig 〇(10), and the eluate is (4) thin layer chromatography (TMnLayerChr_〇graphy) (The ultraviolet light and the detection test development solution are dichloromethane: methanol = 96: 4) The components are detected, and the same components are combined. A 7-tube column chromatography was carried out using a mixture of -chloromethane-methanol (96:4) to obtain 78 g of a PCM portion of the hydrazine extract of the present invention. The PCM part can clearly see 6 traces according to the above-mentioned thin layer chromatography. Chromatography of methylene chloride: methanol (9G: 1G) and (G: 1 (9)) was combined to obtain pcw 168 g, PCM part of the step to dichlorofluor: methanol (96 5:3 5 As a flushing agent, the rubber column chromatography (same as the above-mentioned rubber column) can be further separated to obtain the lanostane-like component K1 (KM and κι_2), Μ (2 1 and Κ 2-2). , Κ3, Κ4, K4a, K4b, Κ5, K6a and K6b. For detailed separation steps and clocking analysis data, see EP 1535619 A1. The above K1 to K6b compounds have the following structure: 15 201039832

Kl-l: R2 = OCOCH3 (pachymic acid) Kl-2: R2 = OCOCH3 (trace) K2-1: R2 = OH (tumulosic acid) (dehydropachymic acid) Ο K2-2: R2 = OH (min) (dehydrotumulosic acid )

❹ K3 : R6=CH3 R5 = H (polyporenic acid C)

K4a : R6=CH2OH R5 = H K6a : R6 = CH3 R5 = OH

K4: R2 = a-OH R5 = H (3-epidehydrotumulosic acid) K4b: R2 = yS-OCOCH3 R5 = OH

K5 16 201039832 The yield of lanosterol compounds K1 to K6b isolated from the PCM fraction is shown in the table below. The PCM portion contains about 15% by weight of the lanosterol compounds K1 to K6b. K1 K2 K3 K4 K4a K4b K5 K6a K6b 3.0 g 6.2 g 1.93 g 0.55 g 66 mg 86.8 mg 47.6 mg 21.4 mg 90.7 mg Example V. Capsule Preparation The hydrazine extract PCM prepared in Example 4 was prepared according to the following composition. Capsules of the ingredients: Ingredients Per capsule per 30,000 capsules The hydrazine extract PCM (containing about 15 wt ° / 〇 K1-K6 compound) prepared by the method of Example 4. 11.2 mg 336.0 g Sodium silicoaluminate 5.0 Mg 150.0 g Starch Potato 378.8 mg 11,364.0 g Mangensium Sterate 5.0 mg 150.0 g Subtotal 400 mg 12,000.0 g The 茯苓 extract PCM and strontium aluminate were respectively #80 mesh ( Mesh) Screened with sieve, potato starch is sieved with #60 mesh screen, magnesium stearate is sieved with #40 mesh sieve, placed in a mixer and stirred evenly, then filled into nickname empty capsules, each capsule Contains about 1.68 mg (0.42 wt ° / 〇) of active ingredient 17 201039832 K1-K6. Example 6 The cockroach extracts prepared in Example 2 and Example 3 of the present invention were respectively formulated with the medicinal agents shown in Table 1 as test substances to evaluate the changes in body weight, food intake and serum protein content of the animals due to cancer. And the overall nutritional status of the sputum extract extract from patients with cachexia caused by cancer. ❹ Table 1: Dose of the extract of the test substance contained in the test substance 茯苓 extract * lanosterol animal dose equivalent human dose PC-A Example 2 17.6 mg / kg 33.6 mg / 70 kg PC-B Example 2 8.8 Mg/kg 16.8 mg/70 kg PC-C Example 2 4.4 mg/kg 8.4 mg/70 kg PC-D Example 3 8.8 mg/kg 16.8 mg/70 kg ❹ *茯苓 extract contains 26% lanosterol compound Example 7 This example is an animal test for treating cachexia caused by cancer with the agent of Table 1. Human lung cancer cells were transplanted into mice to test whether the extract of sputum can have a therapeutic effect on cachexia. Observe the changes of body weight, food intake and serum albumin concentration in human lung cancer cell-transplanted mice and normal mice to evaluate their treatment. The efficacy of cancer cachexia. Experimental animals 18 201039832 Test mice were purchased from the National Taiwan University Animal Center for six to eight weeks old CB- 1 7 SCID mice, which were housed in stainless steel sputum. Room temperature is controlled at 25 ± 2 ° C, humidity range is 40-70%, 12 hours light / dark alternate, drinking water is not limited. After the purchase, the adaptation period was first given in the animal room. After the machine was heavy, the similar weights were grouped into the same group in random numbers. Statistical analysis showed that there was no significant difference in body weight between the groups. The human lung cancer cell line Η 460 qingchun was taken out from the liquid nitrogen tube and stored in the Η460 cell line, thawed in a 37 t water bath and 8 ml of 1% FBS DMEM medium was added to the console, and 1200 After centrifugation at rpm for 10 minutes, the cells were added to 8 ml of the culture solution, and cultured in a we, 5% c〇2 incubator until the desired amount of cells. - - Mouse orthotopic intrusion into lung cancer cell line H460. Deeply anesthetize the mouse with pentobarbital, use a 29 gauge (0.5 g) insulin needle on the mouse chest. After implantation of ΟH46〇 cell line 〇·1 (1x1 〇6/ml) into the rib cavity, the mice were returned to the original mouse cage and allowed to recover by themselves. Drug treatment Example 2 prepared sputum extract is called 67.7 mg to be added to sterile water to 1 〇 mb. Ultrasonic treatment is used to make the extract in suspension and present in solution to form PC-A agent, quantitative 5 ml PC- The A drug is quantified to 10 m in sterile water to form a PC-B agent, and 5 ml of the PC-B agent is quantified in sterile water to 1 〇m b to form a PC-C agent. The mice were fed according to their respective body weights, and the 0.25 CC drug was administered to each mouse body weight of 25 gm tube, and the test was performed on the same amount of Table 1 19 201039832. The normal mouse group (blank) was steamed with water. Normal small A (substituting culture medium pBs for H46Q injected into the chest). Control group (_ίΓ〇1)' was fed with lung cancer mice by steaming water. The arrogant way was to use a syringe (1 cc). No. 8 (length 5 cm) steel tube, hold the mouse double mouth with the left hand when the tube is silver, then carefully put the tube into the stomach, and then pipe the (four) agent or distilled water, each volume does not exceed 〇3 cc The first-person 6-type test was divided into normal group (blank), control group ((3) plus (7)〗) and three groups of sputum-administered group (different lanosterol dose), a total of five groups, 9 mice per group The three groups of the drug-administered group were given PC-A, PC-B and PC-C, respectively, to the lung cancer mice, and the mice were administered with lanosterol per kilogram of body weight. Mg, 8 8 and 44 post, as shown in Table 1. The first test was divided into normal group (blank), control group (control) and giving group-group' Three groups of 3 mice each. The drug-administered group was given the drug PC_D of the cockroach extract prepared in Example 3, and the mice were administered with lanolin 8.8 mg per kilogram of body weight. As shown in the figure, the serum albumin blood sample was collected on the 22nd day, and the whole blood was collected from the corner of the mouse, and the blood sample was allowed to stand at room temperature for 1 hour. It was centrifuged twice at 3,000 rpm, and the collected serum was stored in _2 , it, to be licked. Post-assay analysis of serum albumin content. Serum albumin-enriched assays were performed using a mouse albumin ELISA kit (Bethyl Laboratories Inc., Texas, US) for analysis of reagent kits. Anti-mouse albumin) diluted loo times with TBS, 20 201039832 coated 100 μΐ/well well in a microtiter tray 'at room temperature for 1 hour. After 3 times with TBST', after 1% BSA 200 Ml/weii well Blocking 'Operation at room temperature for 1 hour, then 3 times with tBST. Add sample and standard solution for 1 hour at room temperature, 5 times with TBST, then add 100 μΐ/well of sheep Anti-blood protein-hrp conjugate (G〇at anti-mouse albumin-HRP c Onjugate) Diluted solution (1,000 times diluted with TBS containing 1% BSA and 0.05% Tween 20) at room temperature for 5 hours. Wash 5 times with TBST 'Add 1 〇〇μΐ of matrix solution tmb ( 3,3',5,5'-tetramethylbenzidine), the reaction was stopped at room temperature for 2 minutes in the dark, and the absorbance at A45 〇nm was determined by adding 2NHC1 to the ΙΟΟμΙ/well well. Statistical Methods - Data results are expressed as _meanit standard deviation. The statistical principle first uses one-way ANOVA to characterize the variation between groups. If P< 〇〇5, then Dunnett's multiple range t-test is used to compare the differences between groups. The comparison between each group and the control group is the principle. Changes in body weight and intake The changes in food intake and body weight of each group of mice in the first and second trials were observed. Results Changes in body weight of the mice The first test showed that the change in body weight of the lung cancer mice during the tube feeding of the extract was as shown in Fig. 1. The control group (contr〇i) mice showed a significant decrease in body weight after implantation of H460 lung cancer cells, compared with the implantation of lung cancer cells 21 201039832 Ο ❹ mice re-administered 茯 萃取 extract low dose PC-C (4.4 mg / Kg) and PC-B (8.8 mg/kg) 'There is no difference between the two', ie no improvement in cachexia symptoms. However, if the dose is increased to 17_6 mg/kg (PC-A), the decrease in body weight can be seen in mice, so the sputum component can improve the weight loss caused by the implantation of H460 lung cancer. A second experiment was performed using different sputum extracts, extract PC-D (8.8 mg/kg), and the body weight changes in lung cancer mice are shown in Figure 2. As shown in Figure 1, the control mice showed a significant decrease in body weight after implantation of H46 sputum cells, whereas normal mice (Blank) (not implanted with H46 sputum cells) gained slightly more weight, while pc_D was given sputum extract. The group found that it was able to maintain the body weight at the beginning of the trial, so the tea can treat cachexia' should be proven. Changes in food intake in cancer mice. Lung cancer] The change in food intake after the tube feeding of the extract was shown in Figure 3. In the control group, the food intake gradually decreased after the implantation of η-negative lung cancer cells. Compared with mice administered with lung cancer cells and then given tea extract (PC_D), the intake of food did not show a gradual decline, but it was the same as the normal group (Mack) mice (not implanted with H46 lung cancer). There was no difference in the amount of food intake between the two groups of mice. Therefore, the extract can improve or treat the condition in which the cachexia causes poor feeding. Changes in albumin content in serum of lung cancer mice The changes in white matter in the gray of each group of mice in the first and the third trials are shown in Figure 4 and 阍$仏_3 and Figure 5. The mice in the control group (H460) implanted with lung cancer cells had a tendency to decline relative to tau fire a, with serum albumin right phantom mice (not inoculated with H46 〇). In the feeding of the cockroach extract of the 22 201039832 group (PC-A, B, « ^ ^ ^, L), it was observed that as the dose of lanolin increased, the albumin in the blood of the mice increased in the administration of PC- A significant dose of $1 to 6 mg/kg was observed. In the administration group PLD (8·8 mg/kg dose) administered with sputum extract, } also served the same significant effect. In animals, inflammatory reactions are produced in lung cancer cells. This reaction changes the protein production of hepatocyte proteins. Some proteins reduce manufacturing, and some eggs (or induces protein production) increase. Therefore, in addition to observing changes in body weight and food intake in mice, another method can measure albumin in blood, such as a decrease in albumin blood, indicating that the animal is affected by lung cancer cells, so that the albumin produced by the liver, cells, and cells is reduced. Therefore, albumin is released into the blood. As shown in Fig. 4 and Fig. 5, the blood albumin content of the cachexia mice decreased, but the blood albumin content of the cachexia mice administered with the extract did not decrease. 'The tea extract obviously has the treatment of cachexia. effect. Example 8: Human clinical studies on the treatment of cancer-causing cachexia by 〇 茯苓 extract: (1) Observing the improvement of the overall nutritional status of the patient. (B) Observe the improvement in patient weight. (A) Grouping and administration of cancer patients: 15 cancer patients sustained weight loss, belonging to gastric cancer (3 persons), sputum cancer (3 persons), rectal cancer (3 persons), breast cancer (4 persons), oral cancer (1 person) and nasopharyngeal carcinoma (1) were randomly divided into 3 groups of 5 persons each, and the first group was given low-dose sputum extract (extracted from Example 3 '16.8 mg/each)' per 曰One capsule. The second group was given a higher dose of sputum extract 'two capsules per 23 23 201039832 sac. The third group did not give sputum extracts only to take chemotherapy drugs for comparison purposes. (B) Treatment: 15 patients received chemotherapy for 6 weeks, and patients in the first/second group were treated with sputum for 4 weeks (5/6 weeks for chemotherapy only), and a weight/nutrient status assessment form was recorded weekly. (C) Treatment outcome (―): The weight of the cancer patient is improved. After the treatment (sixth week or 42 days later), the patient's weight is compared with the first day of treatment. The results are as follows: Group treatment (chemotherapy) Weight gain Invariant weight loss The first group added 16.8 mg 茯苓 extract 3 1 1 The second group added 33.6 mg 茯苓 extract 3 1 1 The third group 1 0 4 From the treatment results can be seen given chemotherapy and sputum extract group (/ One group) is the third in the weight maintenance or improving the body weight, and (and (only, Ή chemotherapy without giving sputum), the weight of this group can be observed to reduce the body weight, still lower than the first treatment The weight of the day. (D) Treatment outcomes (II) Improvement of overall nutritional status of patients The overall nutritional status of cancer patients is assessed based on the Patient-Generated Subjective Global Assessment used by clinicians to assess a group of patients ( 1) Weight improvement (2) Diet improvement (3) Improvement of symptoms and (4) Comprehensive scores obtained by the improvement of the body, as shown in Figure 6, Figure VII and Figure 8 below, Figure ', for the first group of patients (chemotherapy +茯苓 extract capsules 1), Figure 7 is the 24th 201039832 two groups of patients (chemotherapy + sputum extract capsules 2) 'Figure 8 for the control group (chemotherapy) ° The lower the PG-SGA score, the better the improvement procedure The whole tends to be healthy. From the treatment results, the administration of sputum extract and treatment with chemotherapeutic drugs far improves the health/life quality improvement of patients with cachexia far beyond that of chemotherapy-only cachexia, and it is statistically significant. The results of this example can be found. The combination of extracts and chemotherapeutic drugs can prevent weight loss in cancer patients, and the overall nutritional status of patients is significantly better than cancer patients who only receive chemotherapy. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the body weight of each group of mice in the first test of Example 7 - change, where + represents the normal group (blank) black dots represent the control group

(control); diamonds, squares, and triangles represent the administration groups pc_A, pc_B, and pc-c, respectively, and the mice were administered lanosterol 17.6 mg, Q 8.8 mg, and 4.4 mg per kilogram of body weight, respectively. Figure 2 shows the change in body weight of each group of mice in the second test of Example 7. wherein the diamond represents the normal group (Mank); the square represents the control group, and the square represents the drug group pc_D, and the mouse per kilogram The body weight was administered 8.8 mg of sterol. Figure 3 shows the food intake culture of each group of mice in the second experiment of Example 7. The diamonds represent the normal group (blank); the triangles represent the control group (control) and the circle represents the administration group pc_D ' mice. Rhenol 8.8 mg was administered per kilogram of body weight. 25 201039832 Figure 4 shows albumin concentration in blood of mice of each group of mice in the first trial of Example 7. Figure 5 shows the albumin concentration in the blood of day 22 of mice in each group of mice in the second trial of Example 7. Figure 6 is an evaluation of the overall nutritional status of the first group of cancer patients (1 chemotherapy + sputum extract capsule) of Example 8 based on the Patient-Generated Subjective Global Assessment used by clinicians. to evaluate. Figure 7 is an evaluation of the overall nutritional status of a second group of cancer patients (2 capsules of chemotherapy + sputum extract capsules) of Example 8, which was evaluated according to the PG-SGA scale used by clinicians. Figure 8 is an evaluation of the overall nutritional status of a control group of cancer patients (chemotherapy) in Example 8, which is based on the PG-SGA scale used by the clinician. ❹ 26

Claims (1)

201039832 VII. Scope of application for patents: 1. A pharmaceutical composition for preventing and treating the consumption of mammals, diseases, including - an effective amount for preventing and treating wasting diseases, lanosterol having the following chemical formula (I) or its medicine Allow _ • effect, knife (I) where R1 is H or CH3; R2 is OCOCH3, =0 or OH; R3 is Η or OH; R4 is -C(=CH2)-C(CH3)2Ra, where 1^ is 11 or OH, Or -CH=C(CH3)-Rb, wherein Rb is CH3 or CH2OH; rule 5 is ruthenium or OH; and Κ6 is CH3 or CH2OH. 2. The pharmaceutical composition according to claim 1, wherein the lanosterol (1) has the following chemical formula: 27 201039832 28 201039832 3. A pharmaceutical composition according to claim 1, wherein the pharmaceutical composition contains from 0.1 to 60% by weight of lanosterol. 4_ The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is orally administered. '5' The pharmaceutical composition of claim 1, wherein the wasting disease is cachexia. G 6. The pharmaceutical composition according to claim 1, wherein the mammal is a human. 7' The pharmaceutical composition according to claim 1, which comprises a sputum extract comprising 1-6% by weight of lanosterol (1) of claim J and substantially 3 open Ring lanosterol. The pharmaceutical group, S substance, which is the seventh item of the patent application, contains 5 to 35 wt% 29 201039832 ' of lanosterol (i). 9. The pharmaceutical composition of claim 7, wherein the lanosterol (I) has the following chemical formula: 〇 30 201039832 A pharmaceutical composition according to claim 5, wherein the cachexia is caused by cancer. II. The pharmaceutical composition according to claim 10, wherein the cancer is lung cancer, stomach cancer, pancreatic cancer, rectal cancer, breast cancer, oral cancer or nasopharyngeal cancer. 12. The pharmaceutical composition of claim 1, wherein the wasting disease is caused by cancer, anorexia, aging, physical injury or burns. 1 3 . The pharmaceutical composition according to claim 6, wherein the lanosterol (I) is administered at a dose of not less than 8.4 mg per mash. 14. The pharmaceutical composition of claim 1, further comprising a pharmaceutical acceptable carrier or diluent. 31