TW200301141A - Manufacturing method and composition of choline type oral lozenge for treating xerostomia - Google Patents

Abstract

This invention discloses a manufacturing method and a composition of choline type oral lozenge for treating xerostomia, which uses pilocarpine hydrochloride as a primary ingredient and adequate amount of microcrystalline cellulose and stearic acid as excipient; lozenges of such medicine are obtained after mixing, pressing and adding coating film, printing and packaging, which can increase secretion of salivary gland and thus has the major effectiveness for improving symptoms of xerostomia.

Description

200301141 V. Description of the invention (1) [Technical field to which the invention belongs] The present invention provides a "method and composition for making choline oral tablets for the treatment of xerostomia", especially a kind suitable for head and neck radiation treatment. Xerostomia caused by atrophy of exocrine glands is a bond containing Pilocarpine hydrochloride as the main component, which can increase the secretion of exocrine after use 'and thus obtain a better saliva secretion and improve Symptoms of dry mouth and prevent complications caused by dry mouth. [Previous technology] According to radiotherapy, for patients with nasopharyngeal cancer, sacral adenocarcinoma, oral cancer, etc., after the radiation treatment of head and neck cancer, it is very easy to cause the reduction of glandular function. Causes annoying xerostomia and dry eyes, especially xerostomia, which makes patients always feel that their mouths are very dry. They often have to take along with them to eat soup and eat them, especially when they sleep at night. Wake up a few times ^ ^ Several times; this is due to the effect of salivary atrophy caused by insufficient radiation of saliva after treatment of radiation; due to the drastic reduction of saliva secretion, the second will not only produce dry mouth sensation, but also affect Food digestion and inhalation because saliva is also one of the digestive fluids that break down food; lack of saliva plus bolus' Many foods eaten into the belly can not be effectively digested and absorbed, saliva affects appetite, so long-term, it will also cause nutrition Disorders; moreover, many ingredients of liquid ^ can help us resist bacteria and mold; therefore, after _ dry mouth disease 'often causes the phenomenon of surname teeth and toothache, but also Yi Long Crane mouth sores (candidiasis), therefore, is not only a xerostomia

Page 4 200301141 V. Description of the invention (2) Symptoms are also the beginning of other complications and should be given more attention. In addition, the atrophy of salivary glands due to complications of autoimmune insufficiency (S j 〇 g r e η ′ s Syndrome) can also cause more severe xerostomia as described above. For the most annoying dry mouth symptoms and complications mentioned above, they usually occur after one week of treatment and reach the highest in the second and third weeks. The principle of care can only be more mouthwash, drink more water and juice to improve the feeling of discomfort You must even bring warm boiled water with you; or you often have vitamin C tablets or hard candy in your mouth to promote saliva secretion. Most of the treatments are not effective and you cannot improve your condition for a long time. [Summary of the Invention] Therefore, the main object of the present invention is to use Pilocarpine hydrochloride as the main component, and add appropriate excipients (for example: microcrystalline cellulose and stearic acid), and then mix and compress Then, add the steps of coating film coating, printing and dyeing and packaging to make lozenges, and make the lozenges have the main effect of increasing salivary gland secretion and improving xerostomia. [Embodiment] The composition of the lozenge of the present invention; including: 1. Active ingredients · Pilocarpine hydrochloride test (ie Pilocarpine hydrochloride) 〇2 · Inactive ingredients (ie excipients): 200301141 V. Description of the invention (3 ) Microcrystalline cellulose and steric acid 〇3. Lozenge film coating: (l) 〇padry or (2) 0padry and pure water Note: (^ 8 (^ The series is a film coating material; while ¥ 3-Bu 700 3 and YS-1-1 8 0 2 7-A are US colorants, white. 4. Lotion brightener: palm wax. 5. Lotion printing Agent: (1) 〇 口 & 〇: 〇 (16,8-1-810 5 black or (2) 0pacode S-1-8085 black, isopropanol USP and / or (3) absolute ethanol SD ( Only use it if needed) Among them, water and alcohol used for film coating or printing and dyeing will be fully evaporated after the drug tablets are finally coated and printed, so the use of these substances has no effect on the final drug shape. The composition ratio of the tablets of the present invention in the above composition is as shown in the following table: Core Components of Tablets_mg per tablet 5.0 mg 92.0 mg 3.0 mg 100.0 mg pomaceae hydrochloride microcrystalline cellulose stearic acid core weight per tablet 200301141 V. Description of the invention (4) Tablet film coating 2.5 mg 2.5 mg Q S (evaporation. 0 0 8mg QSQSQSQS

Opadry YS-1-7003, white or

Opadry YS- 1-1 8 0 2 7-A, pure water tablet brightener brown pick butterfly tablet printing agent black printing ink Opacode S-1-8105, or black printing ink Opacode S-1-8085, such as Need to add isopropanol USP and

Anhydrous ethanol SD: 1. The effective ingredient of pilocarpine hydrochloride per tablet is 5.0 mg. 2. The above-mentioned printing and dyeing agents and alcohols will completely evaporate after the tablets are formed, and will not appear in the final product. [Manufacturing method of the present invention]

Page 7 20031141 V. Description of the invention (5) The method for making a spinner is composed of the above medicines: (A) Mixing 1. Pilocarpine hydrochloride with a total weight percentage of the tablet of about 5-10%, and an appropriate amount For mixing, add about half of the weight of microcrystalline cellulose to a high-cutting blender. 2. Add milled pilocarpine hydrochloride to the microcrystalline cellulose in the blender. 3. Add the remaining microcrystalline cellulose to the blender. 4. Mix finely ground pilocarpine hydrochloride and microcrystalline cellulose 5. Using a sieve with an appropriate size sieve (about 30 mesh), filter the stearic acid with a total weight of about 3%, and filter the stearic acid Add the acid to the stirrer in step 4. 6. Mix stearic acid with the mixture from step 4. 7. Move the mixture from step 6 into a stainless steel cylinder. (B) Compression 1. Use a rotary tablet compressor to compress the mixture into a core of a target weight (for example: 1000 mg). 2. In this step, the tablet core is inspected and tested by the manufacturing quality control staff. (C) Coating film coating 1. Using a tablet coating machine, cover the compressed core with Opadry YS-1-7003, or Opadry YS-1-1 0 0 2 7-A white water sample film. 200301141 V. Description of the invention (6) ----- 2 · Use palm wax to polish the tablet film coating. 3. Sampling, inspection and testing of coated tablets and polished tablets. (D) Printing and Dyeing 1. Use a keypad printing machine, and use Opacode S ~ Bu 8105, or Opacode S-Bu 80 85 black printing ink as the printing tablet. 2. Sampling, inspection and testing of dyed spinning agent. (E) Packaging 1 · Fill an appropriate amount (for example: every 1000 tablets) into a bottle. 2 · Sampling, inspection and testing of packaged and labeled products. A bond for curing xerostomia can be prepared by the above method. [Efficacy of the present invention] The present invention is a cholinergic parasympathomimetic preparation, which can exhibit a wide range of pharmacological effects, especially muscarinic effects; an appropriate dose of Pi locarpine can increase the secretion of exocrine glands; sweat, salivary, lacrimal, and gastric Mucosal cells of the intestinal glands and the respiratory tract can be stimulated; and one hour after using the active ingredient of the present invention "Pomaceae hydrochloride test" 5mg, the patient can increase saliva flow by 63%, taking a 10 mg dose It can increase the amount of saliva by 90%; the flow of the subauricular gland also increases at the same time; therefore, the dose of the active ingredient "Pomaceae hydrochloride rue test" is from 5mg to 10 mg, which can effectively treat radiation therapy for head and neck cancer Causes xerostomia due to decreased salivary gland function; and S j ogren's Syndrome

Page 9 20031141 V. Description of the invention (7) The atrophy of salivary glands, which causes severe xerostomia, enables patients to be better treated, and prevents complications such as dental caries and thrush caused by dry mouth 〇Because of the positive attitude of the inventor for continuous improvement in pursuit of more medical quality, after many developments and efforts, this product has been finally obtained, has the excellent effects as described above, and should meet the requirements for applying for an invention patent. I also ask your reviewing committee to give the invention patent as soon as possible.

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Claims (1)

200301141 VI. Scope of patent application1. A method for manufacturing a choline-based oral lozenge for treating xerostomia, the steps include: (A) Mixing: hydrochloric acid with a total weight percentage of sharpening agent of about 5-10% Pilocarpine hydrochloride and an appropriate amount of microcrystalline cellulose are mixed. Among them, the microcrystalline cellulose and the finely ground pilocarpine hydrochloride are placed in a high-cutting blender and mixed; A sieve with a large sieve hole, filter the appropriate amount of stearic acid, add the filtered stearic acid to the mixer and mix; then move it to the barrel; (B) use a rotary tablet compressor to compress the mixture The core of the target weight; (C) Use a tablet coating machine to coat the film coating, and use (^ & Xin Yaya 3- 1-7 0 0 3 as the film coating to cover the above mixture; then use palm Polish the film coating of the tablets; (D) Printing and dyeing using a tablet printing machine, and printing the key agent with 0.3 (: 0 (168-1-8105 as the key agent printing agent); (E) the packaging will be an appropriate amount Sharps are packed in bottles. 2 · As described in item 1 of the scope of patent application, "Choline Oral Chronic Therapy for the Treatment of Xerostomia: Method for the Preparation of Agents", wherein about half of the weight of microcrystalline cellulose can be added to the mixing step before stirring. Grinder Page 12 20030114i VI. Application scope iSalt ί 5 Rutin is added to the microcrystalline cellulose in the mixer and stirred: The microcrystalline cellulose below is added to the mixing and mixing. 3. = "Treatment; Chronic biliary examination of dysentery ys i times two; go" as described in item 1 above, where "pad" coated with film pad 0j, can be changed to 0padry υπ-1 8 0 2 7-α and water. # 二 Ｍ 二 Ξ 围 Item 1 "The biliary oral oral qi & method for treating xerostomia", wherein the tablet printing agent Opacode S 1 8105 can be changed to 〇pac〇de s-1 -808 5 printing ink to replace. 5. Kinds of bile-experimental oral money for the treatment of xerostomia: the composition of the agent ", which is mainly composed of hair hydrochloride and rutamine (that is, Pilocarpine hydrOchiride); Tablets made from excipients 0 6 · "Composition of a choline-based oral tablet for treating xerostomia" as described in item 5 of the scope of patent application, wherein each tablet contains the main ingredient hair HCl Fruit rue test is between 5 mg and 10 mg. 7 · "Composition of a choline-based oral tablet for treating xerostomia" as described in item 5 of the scope of patent application, wherein the excipients are microcrystalline cellulose, and steric acid ) ° 8 · "Cholesterol test for the treatment of xerostomia, as described in item 5 of the scope of patent application The composition of the doubting agent "" wherein "the outer layer of the lozenge is coated with a lozenge film coating, a spinning agent brightener and a spinning agent dyeing agent. 9. "Composition of a choline-based orally administered lozenge for treating xerostomia" as described in item 8 of the scope of application for patents, wherein the lozenge film coating can be used. Page 13 200301141 6. Scope of patent application YS-; l-7 0 0 3 (white). 10. The composition of a choline-based oral tablet for treating xerostomia as described in item 8 of the scope of the patent application, wherein the tablet film coating can use Opadry YS- 1-1 8 0 2 7-A and Pure water. 1 1. The "composition of choline-based oral sharps for the treatment of xerostomia" as described in item 8 of the scope of the patent application, wherein the bond printing agent can be used 0 pac 〇de S- 1 -8 0 8 5 ( (Black) and will completely evaporate after the tablet has been formed. 12. The composition of the choline-based oral rotator for treating xerostomia as described in item 8 of the scope of the patent application, wherein 0 pac 〇de S-1-8085 can be used as the key printing agent, and an appropriate amount can be used. Isopropanol US P and absolute ethanol SD were added, and they would completely evaporate after the tablets were formed. 1 3. The "composition of a choline-based orally-administered lozenge for treating xerostomia" as described in item 8 of the scope of the patent application, wherein the lozenge brightener is palm wax. Page 14