Title of Invention

LYOPHILIZED POWDER OF LENTINAN

Abstract

An aseptic antineoplastic lyophilized powder of lentinan for injection without dextran, characterized in that it is substantially composed of lentinan 0.50-1 40 parts by weight and lyophilized excipient 50-140 parts by weight. 5 2. An aseptic antineoplastic lyophilized powder of lentinan for injection without dextran, characterized in that it is substantially composed of lentinan 0.70-1.40 parts by weight and lyophilized excipient 70-140 parts by weight. 3. An aseptic antineoplastic lyophilized powder of lentinan for injection without dextran, characterized in that it is substantially composed of lentinan 0.80-1.20 10 parts by weight and lyophilized excipient 80-120 parts by weight. 4. An aseptic antineoplastic lyophilized powder of lentinan for injection without dextran according to any one of claim 1-3, characterized in that its lyophilized excipientmay beany one of mannitol, glucose, sucrose or lactose. 5. An aseptic antineoplastic lyophilized powder of lentinan for injection without 15 dextran according to any one of claim 1-3, characterized in that its lyophilized excipient is mannitol. 6. An acoptio Qntinooplactic lyophilizcd powdor of lentinan for injection as claimed -do substantially heroin deocribod with forgoing doooription and examples. 20 Dated this 17th Day of January 2003. Dr. Rajeshkumar H. Acharya Advocate & Patent Agent For and on behalf of Applicant

Full Text

FORM - 2 THE PATENTS ACT, 1970 COMPLETE SPECIFICATION [Section 10] 1. "Lyophilized Powder of Lentinan 2. (a) NANJING ZHENZHONG BIOENGINEERING COMPANY LTD (b) NANJING NEW@HIGH TECHNOLOGY INDUSTRY DEVELOPMENT ZONE, 210061 Jiangsu, P. R. CHINA. (c) P. R. CHINA GRANTED 5-12-2005 The following specification particularly describes the nature of the invention and the manner in which it is to be performed. Lyophilized powder of lentinan and the process of preparation thereof The present invention relates to a biological response modifier (BRM) and the process of preparing thereof, especially, relates to an aseptic antineoplastic 5 lyophilized powder of lentinan (Chinese commercial name: Tin Dixin produced by Naming Zhenzhong Bioengineering company LTD.) for injection and the process of preparation thereof. Lenlinus edodes contains multifold components such as protein, heteropolysaccharide and lentinan etc. Lentinan is a kind of polysaccharides which io was extracted, separated and purified from lentinus edodes entity by Japanese scholar Chihara.G. the primary structure of which is glucose with the principal chain of B-(13)glucose and side chain of P-(16) glucose. According to the report, Jentinan is a kind of BRM with strong inhibition to several cancers and prophylactic effect to the chemical carcinogen, virus carcinogen, especially to the 15 micrometastasis after operation. At the same time lentinan has many virtues such as small dosage of administration, little side effect and usage safety . Japanese Health Ministry granted lentinan as a new antineoplastic drug to appear on market in 1985. China has imported the Lyophilized powder of lentinan for injection from Japanese Atinomoto and applied it in clinic since 1988. However the formula of 20 Lyophilized powder of lentinan imported from Japan is composed of lentinan, dextran and mannitol. As a kind of product of fermentation, when used in clinic, dextran had been found in several cases that leading to death as its anaphylactic shock. Chinese Patent Application CN-96116294.5 has disclosed a kind of lentinan 25 injection and the process of preparing thereof. Firstly, dissolve the lentinan in sodium hydroxide solution, then add citrate acid to adjust the pH, and achieve the lentinan injection by filtration and disinfection. It may be effective, but it is different from the present invention in dosage form, molecular weight and molecular weight distribution of the main product. It is an object of the present invention to provide a lyophilized powder of lentinan without ingredient that can produce side effect. It is another object of the present invention to provide a process of preparing lyophilized powder of lentinan without ingredient that can produce side effect. 5 It is still an object of the present invention to provide a lyophilized powder of lentinan without dextran. It is also an object of the present invention to provide a process of preparing lyophilized powder of lentinan without dextran. All these and the other objects of the present invention will be illuminated in 10 detail by further description in the following. Aseptic antineoplastic lyophilized powder of lentinan for injection of the present invention is substantially composed of: 0.50—1.40 parts by weight of lentinan, 50— 140 parts by weight of lyophilized excipient. Furthermore, the aseptic antineoplastic lyophilized powder of lentinan for 15 injection of the present invention is substantially composed of: 0.70—1.40 parts by weight of lentinan, 70—140 parts by weight of lyophilized excipient. The aseptic antineoplastic lyophilized powder of lentinan for injection of the present invention is also substantially composed of: 0.80—1.20 parts by weight of lentinan, 80—120 parts by weight of lyophilized excipient. 20 If necessary, the aseptic antineoplastic lyophilized powder of lentinan for injection of the present invention could also be added to other acceptable or mixable additives and therapeutic drugs in medicine. Of course, these additives and therapeutic drugs will not damage the effect of lentinan, and absolutely without dextran. 25 If necessary, it could also be added to or mixed with other antineoplastic. Preferably, the antineoplastic and auxiliary can be bear bile powder, Redsedum, Ginseng, American ginseng, Chinese ester pillar fungus, Lucid ganoderma and Saussurea involucrate and so on. The lyophilized excipient of aseptic antineoplastic lyophilized powder of lentinan for injection of the present invention can be any one of mannitol, glucose, sucrose or lactose, preferably mannitol. If necessary and possible, the mixture of two or three selected from mannitol, glucose, sucrose or lactose also can be used. 5 The process of preparing aseptic antineoplastic lyophilized powder of lentinan for injection of the present invention can include the following steps: 0.50~1.40 parts by weight of lentinan was taken and dissolved completely in the 20~70 parts by weight of alkali solution ,the concentration of alkali solution is 0.5 ~ 1 .Omol/L, and then acid solution was added to neutralize the pH of the solution to 10 6.0—8.0, then mixed with 50-140 parts by weight of lyophilized excipient again, filtered to eliminate the bacteria, subpackaged into ampoule or glass bottle, sealed or gland bushed after lyophilized. Furthermore, the process of preparing the aseptic antineoplastic lyophilized powder of lentinan for injection of the present invention can also include the 15 following steps : 0.70-1.40 parts by weight of lentinan was taken and dissolved completely in the 20~60 parts by weight of alkali solution ,the concentration of alkali solution is 0.5~ 1.Omol/L, and then acid solution was added to neutralize the pH of the solution to 6.0 ~ 8.0, then mixed with 70-140 parts by weight of lyophilized excipient again, filtered to eliminate the bacteria, subpackaged into 20 ampoule or glass bottle, sealed or aland bushed after lyophilized. The process of preparing the aseptic antineoplastic lyophilized powder of lentinan for injection can also include the following steps : 0.80—1.20 parts by weight of lentinan was taken and dissolved completely in the 20—80 parts by weight of alkali solution, the concentration of alkali solution is 0.5—1.Omol/L, and 25 then acid solution was added to neutralize the pH of the solution to 6.0—8.0, then mixed with 40-120 parts by weight of lyophilized excipient again, filtered to eliminate the bacteria, subpackaged into ampoule or glass bottle, sealed or gland bushed after lyophilized. In the process of preparing aseptic antineoplastic lyophilized powder of lentinan 5 for injection of the present invention, the applied lyophilized excipient could be one of mannitol, glucose, sucrose or lactose, preferably mannitol. The applied alkali is sodium hydroxide and the applied acid is hydrochloric acid. In the process of preparing aseptic antineoplastic lyophilized powder of lentinan for injection of the present invention, lentinan is mixed evenly with lyophilized to excipient, and then filtered to eliminate the bacteria, determining the content (the content determined by the classical anthrone-sulfuric process), filled into the ampoule or glass bottle, lyophilize, sealed or gland bushed, leak checked, paste labeled. The procedures before sealed or gland bushed should be proceeded under asepsis condition. 15 The applied lentinan of the present invention includes single lentinan and multi-component lentinan, which are well-known in the prior art and can be obtained from market. Furthermore, the extraction, separation, purification of lentinan could be referred to Nature 1965, 222, 687-8 and CN-94115876 and the other patent or non-patent documents. These documents mentioned above are incorporated into 20 the present invention herein. The lyophilized powder of lentinan for injection of the present invention is used before operation or before chemotherapy, 1~2 mg each time, twice a week; or 2 mg each time, once or twice a week. When applied, the lyophilized powder of lentinan for injection should be dissolved in 250ml saline or glucose solution, and 25 administered by phleboclysis. When treating the malignant pleural effusion and ascites, the dosage is 4-8 mg each time by intracavitary. Specific case should obey the doctor's prescription. The lyophilized powder of lentinan for injection of the present invention has been tested in clinic and its clinic effect is definite, the stability of preparation is very good and because it does not contain the dextran that could bring the side effec anaphylaxis, its application in clinic is more safety. Moreover, because it does containing dextran in the lyophilized powder of lentinan, its content determine need not separation the dextran by special column chromatography equipment i the classical anthrone-sulfuric process can be applied directly, which make content determination more accurate and simple. I. The molecular weight , molecular formula , chemical structural formula of product of the present invention 1. The determination of molecular weight By high performance gel permeation chromatography and universal corretf curve, most of its molecular weight is determined to be between 400,000 ; 800,000 Dalton. 2. Carbon-nuclear magnetic resonance spectrum (Tab. 1) Tab. 1 15 3. Figure of Infra-red spectrum (Fig. 1) 4. Molecular formula The result by the trace of element analysis indicates that its molecular formul (C6Hio05) n 5. Chemical structural formula Combined the chemical reaction such as Periodic acid reaction, Smith degradation reaction with optical spectrum analysis, the primary structure of the lentinan displays as the following: 5 II. Result and conclusion of the stability of the preparation Tested by the influencing factor test such as the high-temperature test (40 °C, 60 °C, 80°C), high-humidity test (RH92.5%, RH75%, 25°C) and light irradiation test (4000Lx), appearance character, clarity after dissolving, pH value, content, impurity and asepsis test of the product of the present invention meet the request 10 After three-month speed-up test (40°C RH 75%), the review result shows that the appearance character, clarity after dissolving, pH value, content, impurity and asepsis test of the product of the present invention meet the request. The product of the present invention was observed and analyzed respectively in 1, 3, 5, 12, 18 and 24 month at room temperature after being prepared. By way of 15 the periodical check of the samples, all items meet the request. So the effective period is at least two years. All raw materials and excipient of the present invention could be obtained from market. The applied excipients are solid for injectable grade except pointing out specially. 20 The following examples will further indicate the present invention. Although the examples are limited in description, it can not limit the extent of the application of the present invention. In the present invention, all the portions and quantities are the unit of weight based on the gross weight other than mentioned specially. Example 1 The example uses clinical trial phase II and III to prove the excellent effect of the lyophilized powder of lentinan for injection of the present invention. I. Clinical trial of the phase II: The double-blind process and stochastic process are adopted to proceed the clinical trial of the phase n via the hospital appointed by nation. Combined chemotherapy and placebo (lyophilized powder) being the controlling group and combined chemotherapy and lyophilized powder of lentinan being the testing group, 240 patients with different kinds of cancer are tested. The result illuminates that there are CR+PR 67 examples in the 108 examples of the testing group, and the total effective rate is 62%; CR+PR 44 examples in 104 examples of the controlling group, and the total effective rate is 43.2%. Compared both result, the P 33.3%, the total effective rate of the controlling group is 11.5%, the P^0.05. Compared the effect of pre-treatment and post-treatment, the variation rate of lymphocytic cell conversion, NK cytoactive and the rate of T4/T8 of the testing group are remarkablely higher than those of the controlling group, the PO.01. The effective rate of preliminarily using the lentinan to treat the malignant pleural effusion and ascites is 76.5% (13/17), which is similar to that of the foreign literature. II. The clinical trial of the phase III: Under the leading of Chinese Medical Association, the Cancer Hospital of Zhongshan Medical University as the responsible hospital, about 40 hospitals in China take part in the clinical trial of the phase III and examines further the clinical effect and the adverse reaction of the lentinan. They complete the 1106 evaluable cases, including 1047 cases with systemic administration and 59 cases with s malignant pleural effusion and ascites. 1. The total effective rate of the combined chemotherapy group (565 cases) is 41.1%, Compared with the controlling group (301 cases) which is 25.2%, the effective rate of the two groups are of significant difference (P the total effective rate of gastric cancer and NSCLC are obviously higher than 10 the controlling group (P have the chemotherapy enhancement effect of NSCLC hasn't been reported before. 2. malignant pleural effusion and ascites: the total effective rate is 52.5% in 59 cases. 15 3. At the same time, this test also observes the patients' variation of cellular immune function, and the result shows that the three testing index (NK cytoactive, T3, T4/8) are obviously higher than that of the controlling group, and all kinds of main cases display that the lentinan's value enhances the function of cellular immunity 20 4. Active state (PS) There are 1647 cases in the group. The PS of 28.5% patients in the combined chemotherapy group (565 cases) have been improved after treatment (post-treatment compared with pretreatment, there exists significant difference, P 25 (compared with pretreatment, there have no significant difference after treatment, P>0.05), compared with the controlling group, the testing group have significant difference (P Combined chemotherapy, post-operation combined chemotherapy: The falling incidence rate of WBC.Pt in testing group is significantly lower than that of the controlling group (P 5 of the controlling group fP like products of Japanese Atinomotocompany have this very effect. 6. Side-effect Only three cases of side-effect occurred, occupying 0.27% among the 1121 cases that applied lentinan systemically, including two cases of facial flush, one 10 case of chest discomfort, which could restore in short time after slowing the drip speed or withdrawing drug. In 469 cases of the clinical trial of the phase II, III of Japanese product, 32 cases of side-effect occured, occupying 6.8%. Example 2: 15 2.00g lentinan material for injection (purity 98%) was taken, 60ml 1M sodium hydroxide solution was added. The lentinan was swelt naturally, then stirred to make them dissolve completely. Small amount of water for injection was added to dilute, then stirred equally. 1M hydrochloric acid was added to neutralize the pH of the solution to 6.8-7.0 1000ml commercial 20% mannitol injection solution was 20 added, and stirred equally, aseptic filtrated, the content (the content determination used the classical anthrone-sulfuric process) was determined. Water for injection was added to achieve the concentration that each 2ml solution contains 1mg lentinan, subpackaged into 2ml/ampoule or bottle, then lyophilized and dried, sealed or gland bushed, leak checked, eye checked, labeled and the end product 25 was achieved at last. Example 3: 3g lentinan for injection was taken, dissolved fractionally in 100ml 0.8M sodium hydroxide solution when stirred until completely dissolved, and then 0.8M hydrochloric acid was slowly added to neutralize the pH of the solution to 7.0-7.2. Getting 300g commercial mannitol for injection was taken, and 1600ml water for injection was added and to dissolve it by heating, then 0.1% W/V activated carton for injection was added and heated for 15min at 85V, filtered by using No.3 sand core filter candle when cooled to 60°C, then the lentinan solution was added into the filtering solution, thereafter proceed asepsis filtration by using the filter membrane, the content was determined, then water for injection was added to achieve the concentration that each 2ml solution contain 1.5mg lentinan, the ampoule was filled to 2ml/ampoule, moved into the freezing room to be lyophilized and dried , then it was taken out and the ampoule or bottle was sealed or gland bushed, leak checked and labeled, and the end product was achieved at last. Example 4: 4.00g lentinan material for injection (purity 98%) ( obtained from market) was taken, 120ml 1M sodium hydroxide solution was added. The lentinan was swelt naturally, then stirred to make them dissolve completely. Small amount of water for injection was added to dilute, then stirred equally. 1M hydrochloric acid was added to neutralize the pH of the solution to 6.8~7.0. 400g mannitol injection was added, and water for injection was added until the total volume was 3200ml, stirred equally and aseptic filtrated, the content was determined. Water for injection was added to achieve the concentration that each 2ml solution contains 2mg lentinan, subpackaged into 2ml/ampoule or bottle, then lyophilized and dried, decrated , sealed or gland bushed, leak checked, eye checked and labeled. Example 5: 2.00g lentinan material for injection (purity 98%) was taken, 6©60ml 1M sodium hydroxide solution was added. The lentinan was swelt naturally, then stirred to make them dissolve completely. Suitable amount of water for injection was added to dilute, then stirred equally. 1M hydrochloric acid was added to neutralize the pH of the solution to 6.8~7.0. 200g glucose for injection was added, and 1600ml water for injection was added, stirred equally and aseptic filtrated, the content was determined. Water for injection was added to achieve the concentration that each 2ml solution contains 2mg lentinan, subpackaged into 2ml/ampoule or bottle, then 5 lyophilized and dried, decrated , sealed or aland bushed, leak checked, eye checked and labeled. Example 6: 2.00g lentinan material for injection (purity 98%) was taken, 60ml 1M sodium 10 hydroxide solution was added. The lentinan was swelt naturally, then stirred to make them dissolve completely. Suitable amount of water for injection was added to dilute, then stirred equally. 1M hydrochloric acid was added to neutralize the pH of the solution to 6.8-7.0. 200g lactose for injection was added, and 3200ml water for injection was added, stirred equally and aseptic filtrated, the content was 15 determined. Water for injection was added to achieve the concentration that each 2ml solution contains 1mg lentinan, subpackaged into 2ml/ampoule or bottle, then lyophilized and dried, decrated , sealed or aland bushed, leak checked, eye checked and labeled. 20 Example 7 6.00g lentinan material for injection (purity 98%) was taken, 180ml 1M sodium hydroxide solution was added. The lentinan was swelt naturally, then stirred to make them dissolve completely. Small amount of water for injection was added to dilute, then stirred equally. 1M hydrochloric acid was added to neutralize the pH of 25 the solution to 6.8-7.0. 400g mannitol for injection was added, and 3200ml water for injection was added, stirred equally and aseptic filtrated, the content was determined. Water for injection was added to achieve the concentration that each 2ml solution contains 3mg lentinan, subpackaged into 2ml/ampoule or bottle, then lyophilized and dried, decrated, sealed or gland bushed, leak checked, eye checked and labeled. Example 8: 6.00g lentinan material for injection (purity 98%) was taken, 180ml 1M sodium 5 hydroxide solution was added. The lentinan was swelt naturally, then stirred to make them dissolve completely. Small amount of water for injection was added to dilute, then stirred equally. 1M hydrochloric acid was added to neutralize the pH of the solution to 6.8-7.0. 400g glucose for injection was added, and 3200ml water for injection was added, stirred equally and aseptic filtrated, the content was 10 determined. Water for injection was added to achieve the concentration that each 2ml solution contains 3mg lentinan, subpackaged into 2ml/ampoule or bottle, then lyophilized and dried, decrated » sealed or aland bushed, leak checked, eye checked and labeled. 15 Example 9: 8.00g lentinan material for injection (purity 98%) was taken, 240ml 1M sodium hydroxide solution was added. The lentinan was swelt naturally, then stirred to make them dissolve completely. Small amount of water for injection was added to dilute, then stirred equally. 1M hydrochloric acid was added to neutralize the pH of 20 the solution to 6.8-7.0. 400g sucrosem for injection was added, and 3200ml water for injection was added, stirred equally and aseptic filtrated, the content was determined. Water for injection was added to achieve the concentration that each 2ml solution contains 4mg lentinan, subpackaged into 2ml/ampoule or bottle, then lyophilized and dried, decrated , sealed or oland bushed, leak checked, eye 25 checked and labeled. Example 10: 8.00g lentinan material for injection (purity 98%) was taken, 240ml 1M sodium hydroxide solution was added. The lentinan was swelt naturally, then stirred to make them dissolve completely. Small amount of water for injection was added to dilute, then stirred equally. 1M hydrochloric acid was added to neutralize the pH of the solution to 6.8-7.0. 400g glucose for injection was added, and 3100ml water for injection was added, stirred equally and aseptic filtrated, the content was determined. Water for injection was added to achieve the concentration that each 2ml solution contains 4mg lentinan, subpackaged into 2ml/ampoule or bottle, then lyophilized and dried, decrated, sealed or aland bushed, leak checked, eye checked and labeled. Example 11: 8.00g lentinan material for injection (purity 98%) was taken, 240ml 1M sodium hydroxide solution was added. The lentinan was swelt naturally, then stirred to make them dissolve completely. Small amount of water for injection was added to dilute, then stirred equally. 1M hydrochloric acid was added to neutralize the pH of the solution to 6.8-7.0. 400g lactose for injection was added, and 3100ml water for injection was added, stirred equally and aseptic filtrated, the content was determined. Water for injection was added to achieve the concentration that each 2ml solution contains 4mg lentinan, subpackaged into 2ml/ampoule or bottle, then lyophilized and dried, decrated , sealed or gland bushed, leak checked, eye checked and labeled. Example 12: Besides using lentinan for injection 8.0g (purity 98%), adding 240ml 0.8M sodium hydroxide solution, adding hydrochloric acid solution to adjust the pH of the solutionto 6.0»'6.06.2-6.4. and then adding mannitol for injection 400g and adding water for injection 3100ml, the rest is the same as example 11. Example 13: Besides using lentinan for injection 4.0g (purity 98%), adding 200ml 0.8M sodium hydroxide solution, adding hydrochloric acid solution to adjust the pH of the solution pH to 6.3-6.4, and then adding lactose for injection 200g, adding water for injection 3100ml, the rest is the same as example 5. 5 Example 14: Besides using lentinan for injection 4.0g (purity 98%), adding §Q200mJ 0.8M sodium hydroxide solution, adding hydrochloric acid solution to adjust the pH of the solution to 6.5-6.6, and then adding sucrose for injection 200g, adding water for 10 injection 3100ml, the rest is the same as example 4. Example 15: Besides using lentinan for injection 1.0g (purity 98%), adding ©060ml 0.8M sodium hydroxide solution, adding hydrochloric acid solution to adjust the pH of the 15 solution to 6.0«'6.36.6-6.8. and then adding mannitol for injection 200g, adding water for injection 3100ml, the concentration being 0.5mg each 2ml, the rest is the same as example 4. Example 16: 20 Besides using lentinan for injection 1.0g (purity 98%), adding §060ml 1M sodium hydroxide solution, adding hydrochloric acid solution to adjust the pH of the solution to 7.0-7.2, and then adding glucose for injection 200g, adding water for injection 3200ml, the rest is the same as example 15. 25 Example 17: Besides using lentinan for injection 1.0g (purity 98%), adding 60ml 0.8M sodium hydroxide solution, adding hydrochloric acid solution to adjust the pH of the solution to 7.4-7.6, and then adding sucrose for injection 200g, adding water for injection 3200ml, the rest is the same as example 15. Example 18: Besides using lentinan for injection 1.0g (purity 98%), adding £©60ml 0.8M sodium hydroxide solution, adding citric acid solution to adjust the pH of the solution to 7.6-7.8, and then adding lactose for injection 200g, adding water for injection 3200ml, the rest is the same as example 15. Example 19: Besides using lentinan for injection 2.0g (purity 98%), adding 60ml 0.8M sodium hydroxide solution, adding hydrochloric acid solution to adjust the pH of the solution to 7.8-8.0, and then adding mannitol for injection 20Qg, adding water for injection 3100ml, the rest is the same as example 6. Example 20: Besides using lentinan for injection 2.0g (purity 98%),adding S©60ml 1.0M sodium hydroxide solution.adding hydrochloric acid solution to adjust the pH of the solution to 7.8-8.0, and then adding glucose for injection 100g, adding mannitol for injection 100g, adding water for injection 3100ml, the rest is the same as example 6. Example 21: Besides using lentinan for injection 2.0g (purity 98%), adding 100ml 1.0M sodium hydroxide solution, adding hydrochloric acid solution to adjust the pH of the solution to 7.0-7.1, and then adding lactose for injection 100g, adding mannitol for injection 100g, adding water for injection 3000ml, the re,st is the same as example 6. In the present invention, the examples are only used to illuminate. But they can not limit the extent of the claim of the present invention, any improvement and alternation should be calculated into the extent of the present invention and be limited by the claim of the present invention. Amended application We claim: 1. An aseptic antineoplastic lyophilized powder of lentinan for injection without dextran, characterized in that it is substantially composed of lentinan 0.50-1 40 parts by weight and lyophilized excipient 50-140 parts by weight. 5 2. An aseptic antineoplastic lyophilized powder of lentinan for injection without dextran, characterized in that it is substantially composed of lentinan 0.70-1.40 parts by weight and lyophilized excipient 70-140 parts by weight. 3. An aseptic antineoplastic lyophilized powder of lentinan for injection without dextran, characterized in that it is substantially composed of lentinan 0.80-1.20 10 parts by weight and lyophilized excipient 80-120 parts by weight. 4. An aseptic antineoplastic lyophilized powder of lentinan for injection without dextran according to any one of claim 1-3, characterized in that its lyophilized excipientmay beany one of mannitol, glucose, sucrose or lactose. 5. An aseptic antineoplastic lyophilized powder of lentinan for injection without 15 dextran according to any one of claim 1-3, characterized in that its lyophilized excipient is mannitol. 6. An acoptio Qntinooplactic lyophilizcd powdor of lentinan for injection as claimed -do substantially heroin deocribod with forgoing doooription and examples. 20 Dated this 17th Day of January 2003. Dr. Rajeshkumar H. Acharya Advocate & Patent Agent For and on behalf of Applicant

Documents:

79-mumnp-2003-claim(granted)-(05-12-2005).pdf

79-mumnp-2003-claim(granted)-(5-12-2005).doc

79-mumnp-2003-correspondence(05-12-2005).pdf

79-mumnp-2003-correspondence(ipo)-(05-04-2006).pdf

79-mumnp-2003-form 1(05-12-2005).pdf

79-mumnp-2003-form 1(20-01-2003).pdf

79-mumnp-2003-form 18(24-01-2005).pdf

79-mumnp-2003-form 2(granted)-(05-12-2005).pdf

79-mumnp-2003-form 2(granted)-(5-12-2005).doc

79-mumnp-2003-form 26(05-12-2005).pdf

79-mumnp-2003-form 3(05-12-2005).pdf

79-mumnp-2003-form 3(17-01-2003).pdf

79-mumnp-2003-form 5(17-01-2003).pdf

79-mumnp-2003-form-pct-ipea-409(20-01-2003).pdf

79-mumnp-2003-form-pct-isa-210(20-01-2003).pdf