WO2022206716A1 - 含有促肾上腺皮质激素或其衍生物的药物及其用途 - Google Patents
含有促肾上腺皮质激素或其衍生物的药物及其用途 Download PDFInfo
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- WO2022206716A1 WO2022206716A1 PCT/CN2022/083523 CN2022083523W WO2022206716A1 WO 2022206716 A1 WO2022206716 A1 WO 2022206716A1 CN 2022083523 W CN2022083523 W CN 2022083523W WO 2022206716 A1 WO2022206716 A1 WO 2022206716A1
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- Prior art keywords
- chitosan
- salt
- acid
- chitin
- application according
- Prior art date
Links
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- A61K38/35—Corticotropin [ACTH]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
Definitions
- the invention belongs to the technical field of biomedicine, and in particular relates to a medicine containing adrenocorticotropic hormone or a derivative thereof and use thereof.
- Adrenocorticotropic Hormone is a polypeptide hormone secreted by the vertebrate pituitary gland, which can promote the tissue proliferation of the adrenal cortex and the production and secretion of corticosteroids. Corticotropin production and secretion are directly regulated by hypothalamic corticotropin-releasing factor. Excessive secretion of corticosteroids can in turn affect the pituitary gland and hypothalamus, reducing their activity. Adrenocorticotropic hormone has the effect of stimulating the development and function of the adrenal cortex, mainly acting on the adrenal cortical zona fasciae and stimulating the secretion of glucocorticoids. ACTH also has the effect of regulating antibody production through the adrenal cortex.
- Adrenocorticotropic hormone is a polypeptide drug, which is easily hydrolyzed by digestive enzymes in the gastrointestinal tract, and has not been able to be administered orally;
- the clinically used medicinal preparation containing adrenocorticotropic hormone is an injection preparation: adrenocorticotropic hormone for injection (Corticotropin for injection), the indications are for active rheumatism, rheumatoid arthritis, lupus erythematosus and other collagen diseases; also for severe bronchial asthma, severe dermatitis and other allergic diseases and acute leukemia, Hodgkin's disease, etc.
- the present invention is achieved through the following technical solutions.
- the adjuvants in the oral pharmaceutical preparation are: surfactant, acrylic polymer, chitin or its derivative, and metal ion chelating agent.
- auxiliary materials in the oral pharmaceutical preparation are: surfactant, chitin or its derivative, and metal ion chelating agent.
- the surfactants mentioned therein include one or more of anionic surfactants or nonionic surfactants.
- the acrylic polymer described therein includes one or more of Carbomer, Carbomer 910, Carbomer 934 and Carbomer 934P.
- the chitin or its derivatives include chitin, chitosan, carboxymethyl chitosan, acylated chitosan, alkylated chitosan, hydroxylated chitosan, chitosan quaternary ammonium salt , one or more of chitosan oligosaccharide and chitosan sulfate.
- the metal ion chelating agent includes citric acid or its salt, tartaric acid or its salt, malic acid or its salt, maleic acid or its salt, gluconic acid or its salt, EDTA or its salt, amino acid One or more of triacetic acid or its salt, diethylenetriaminepentaacetic acid or its salt.
- the weight ratio of surfactant, acrylic polymer, chitin or its derivatives and metal ion chelating agent is 19-21:6-7:6-7:60-70.
- the weight ratio of surfactant, chitin or its derivatives and metal ion chelating agent is 19-21:6-7:60-70.
- the weight ratio of ACTH (or its derivatives), surfactant, acrylic polymer, chitin or its derivatives and metal ion chelating agent is 1.5-2.5:19-21:6-7:6-7:60 -70.
- the weight ratio of ACTH (or its derivatives), surfactant, chitin or its derivatives and metal ion chelating agent is 1.5-2.5:19-21:6-7:60-70.
- the weight ratio of ACTH (or its derivatives), surfactant, acrylic polymer, chitin or its derivatives and metal ion chelating agent is 0.20-0.30:19-21:6-7:6-7:60 -70.
- the weight ratio of ACTH (or its derivatives), surfactant, chitin or its derivatives and metal ion chelating agent is 0.20-0.30:19-21:6-7:60-70.
- the weight ratio of ACTH (or its derivatives), surfactant, acrylic polymer, chitin or its derivatives and metal ion chelating agent is 0.25-2.0:19-21:6-7:6-7:60 -70.
- the weight ratio of ACTH (or its derivatives), surfactant, chitin or its derivatives and metal ion chelating agent is 0.25-2.0:19-21:6-7:60-70.
- the preferred proportional relationship is: the weight ratio of ACTH (or its derivative), surfactant, chitin or its derivative and metal ion chelating agent is 0.25-2.0:19-21:6- 7:60-70.
- the concentration of the adrenocorticotropic hormone described therein is 0.05 mg/ml or higher in the solution formulation, and 0.4 mg or higher in the capsule formulation.
- Described solution preparation formula concentration refers to more than or equal to 0.05mg/ml, to the saturated concentration in the aqueous solution;
- the capsule preparation refers to that the filling amount in each capsule is greater than or equal to 0.4 mg, up to the maximum filling amount of one capsule.
- the adrenocorticotropic hormone or its derivatives include ACTH(1-39), ACTH(1-24) and ACTH(1-17).
- the adrenocorticotropic hormone (ACTH) of the present invention is a polypeptide hormone secreted by the vertebrate pituitary gland, which can promote the tissue proliferation of the adrenal cortex and the production and secretion of corticosteroids.
- ACTH contains 39 amino acids, of which amino acids 1 to 24 are essential amino acids for biological activity, and amino acids 25 to 39 are protective amino acids.
- adrenocorticotropic hormone (ACTH)
- corticotropin for injection corticotropin for injection
- the present invention obtains adrenocorticotropic hormone (ACTH) or its derivative by oral administration
- Oral pharmaceutical composition as the active ingredient for the treatment of arthritis, including gout.
- the adrenocorticotropic hormone derivatives described in the present invention include but are not limited to: ACTH(1-24), ACTH(1-24) is the N-terminal 24 peptide of adrenocorticotropic hormone.
- ACTH (1-24) because amino acids 1-24 are essential amino acids for biological activity, therefore, it has the same physiological activity as ACTH, and the preparation of oral drugs must have the same ability to treat arthritis, including gout caused by high uric acid. effect.
- Arthritis generally refers to inflammatory diseases that occur in human joints and their surrounding tissues, caused by inflammation, infection, degeneration, trauma or other factors, and can be divided into dozens of types.
- the clinical manifestations are joint redness, swelling, heat, pain, dysfunction and joint deformity, and severe cases lead to joint disability and affect the quality of life of patients.
- the etiology of arthritis is complex, mainly related to autoimmune reactions, infections, metabolic disorders, trauma, degenerative diseases and other factors. According to the etiology, arthritis can be divided into bone, rheumatoid, rheumatic, gout and so on. There are more than 100 million arthritis patients in my country, and the number is increasing, especially gouty arthritis.
- Gout is a common and complex type of arthritis that can affect all age groups, with a higher incidence in men than in women.
- Patients with gout often experience sudden joint pain at night. The onset is acute, with severe pain, edema, redness, and inflammation in the joints. The pain gradually decreases until it disappears, lasting several days or weeks. When the pain strikes (acute gout), the patient wakes up in the middle of the night with pain, and some patients describe the pain as similar to the burning of the big toe.
- the most commonly affected joint is the big toe (medical term: first metatarsal), but the affected joint is not limited to this, and is also commonly found in the joints of the hands, knees, elbows, and the like. The affected joint will eventually become red, swollen and inflamed. After edema, the tissue becomes soft and the movement is limited, which finally affects daily life. These symptoms will recur.
- anionic surfactants, nonionic surfactants, etc. described in the present invention can all be purchased through commercial channels.
- the acrylic polymers described in the present invention include carbomer, carbomer 910, carbomer 934, and carbomer 934P, which can be purchased through commercial channels.
- the chitin or its derivatives of the present invention include chitin, chitosan, carboxymethyl chitosan, acylated chitosan, alkylated chitosan, hydroxylated chitosan, quaternary ammonium chitosan Salts, chitosan oligosaccharides, and chitosan sulfates can all be purchased commercially.
- the metal ion chelating agent of the present invention includes citric acid or its salt, tartaric acid or its salt, malic acid or its salt, maleic acid or its salt, gluconic acid or its salt, EDTA or its salt, Aminotriacetic acid or its salt, diethylenetriaminepentaacetic acid or its salt can all be purchased through commercial channels.
- ACTH or its derivatives, surfactants, chitin or its derivatives, and metal ion chelating agents are formed into new compositions, which are used for the treatment of arthritis after oral administration, Especially gout caused by high uric acid.
- ACTH or its derivatives, surfactants, acrylic polymers, chitin or its derivatives, and metal ion chelating agents are formed into new compositions, and after oral administration, with For the treatment of arthritis, especially gout caused by high uric acid.
- the preferred composition for oral treatment of gout of the present invention is: ACTH or its derivatives, and surfactants, chitin or its derivatives, and metal ion chelating agents to form a new composition; the reason is: three components are selected and ACTH After the combination of its derivatives, it has a good therapeutic effect on arthritis (including gout caused by high uric acid), and on the basis of reducing the components in the composition, it has better safety, and at the same time, it reduces the cost, reduces the burden on patients, etc. advantage.
- the following tests of the present invention are conclusive tests of researchers and researchers based on the technical solutions to be protected by the present invention on the basis of many creative tests.
- the quantitative experiments in the following test examples are all set up three repeated experiments, and the data are the average or the mean ⁇ standard deviation of the three repeated experiments.
- Test 1 Effect test on joint swelling (gout) caused by hyperuric acid in mouse model
- adrenocorticotropic hormone 0.5mg/ml
- sodium lauryl sulfate 4mg/ml
- chitosan 1.3mg/ml
- sodium citrate 13mg/ml.
- the small intestine administration volume was 4 ml/kg.
- Five-component low-dose group adrenocorticotropic hormone 0.05mg/ml, sodium lauryl sulfate 4mg/ml, carbomer 1.3mg/ml, chitosan 1.3mg/ml, sodium citrate 13mg/ml ml.
- the small intestine administration volume was 4 ml/kg.
- Single active ingredient group adrenocorticotropic hormone 0.5mg/ml.
- the small intestine administration volume was 4 ml/kg.
- Positive control group normal saline.
- the small intestine administration volume was 4 ml/kg.
- Test method After 6-8 weeks of C57 male mice were anesthetized by chloral hydrate and xylazine, 50 ⁇ l of 20 mg/ml sodium urate was injected into the right hind paw, and 50 ⁇ l of normal saline was injected into the left hind paw. Half an hour later, according to the grouping situation, a small mouth was opened in the abdominal cavity, and 4 ml/kg of the test drug was administered through the small intestine, with 6 mice in each group. Taking the sodium urate administration as the 0 point, the diameters of the left and right hind paws were measured at 0, 6, 12 and 24 h, and each animal was measured three times at each time point to reduce the operation error. The effectiveness of the drug was assessed by comparing the ratio of the diameter of the right hind paw to the diameter of the left hind paw.
- a p valu ⁇ 0..05 vs positive control group (no drug); b: p value ⁇ 0.01 vs positive control group (no drug)
- the four-component group (the combination of ACTH and sodium lauryl sulfate, chitosan, and sodium citrate) has a 24-hour effect on joint swelling caused by high uric acid; similarly, the five-component high-dose group also has an effect that lasts 24 hours.
- Test 2 The effect of hyperuric acid-induced joint swelling (gout) on the Beagle dog model
- Five-component drug group Enteric-coated capsule No. 3, containing adrenocorticotropic hormone 4mg, sodium lauryl sulfate 40mg, carbomer 13mg, chitosan 13mg, and sodium citrate 130mg. oral.
- Single active ingredient group Enteric-coated capsule No. 3, containing 4 mg of adrenocorticotropic hormone. oral.
- Positive control group No. 3 hollow enteric-coated capsules. oral.
- Test method Male beagle dogs of 6-8 weeks were orally administered different test drugs according to the grouping. After 1 h, the animals were immobilized, and 1 ml of 20 mg/ml sodium urate was injected into the right hind paw, and 1 ml of normal saline was injected into the left hind paw. 3 animals per group. Taking the sodium urate administration as the 0 point, the diameters of the left and right hind paws were measured at 0, 6, 12 and 24 h, and each animal was measured three times at each time point to reduce the operation error. The effectiveness of the drug was assessed by comparing the ratio of the diameter of the right hind paw to the diameter of the left hind paw.
- a p valu>0.05 vs positive control group (no drug); b: p value ⁇ 0.01 vs positive control group (no drug)
- Test results The test shows (as shown in Table 2) that the preparation of adrenocorticotropin into an oral preparation has a very good relieving effect on joint swelling (gout) caused by high uric acid in beagle dogs.
- Adrenocorticotropic hormone 4g sodium lauryl sulfate 40g, carbomer 13g, chitosan 13g, sodium citrate 130g.
- Preparation method take sodium lauryl sulfate, carbomer, chitosan, and sodium citrate respectively, crush and sieve, mix them with adrenocorticotropic hormone, and put them into enteric-coated capsules to get it.
- Adrenocorticotropic hormone 4g sodium lauryl sulfate 40g, Bohm 934P 13g, carboxymethyl chitosan 13g, sodium malate 130g.
- Preparation method take sodium lauryl sulfate, pomer 934P, carboxymethyl chitosan, and sodium malate respectively, crush and sieve, mix with adrenocorticotropic hormone evenly, and put them into enteric-coated capsules.
- Adrenocorticotropic hormone 4g sodium lauryl sulfate 40g, Bohm 934 13g, acylated chitosan 13g, sodium malate 130g.
- Preparation method take sodium lauryl sulfate, pomer 934, acylated chitosan and sodium malate respectively, crush and sieve, mix with adrenocorticotropic hormone, and put them into enteric-coated capsules to get it.
- Adrenocorticotropic hormone 5g sodium lauryl sulfate 400g, carbomer 130g, chitosan 130g, sodium citrate 1300g.
- Preparation method take sodium lauryl sulfate, carbomer, chitosan, and sodium citrate respectively, crush and sieve, mix them with adrenocorticotropic hormone, and put them into enteric-coated capsules to get it.
- Adrenocorticotropic hormone 4g sodium lauryl sulfate 40g, chitosan 13g, sodium citrate 130g.
- Preparation method take sodium lauryl sulfate, chitosan and sodium citrate respectively, crush and sieve, mix them with adrenocorticotropic hormone evenly, and put them into enteric-coated capsules.
- Adrenocorticotropic hormone 4g sodium lauryl sulfate 40g, carboxymethyl chitosan 13g, sodium malate 130g.
- Preparation method take sodium lauryl sulfate, carboxymethyl chitosan and sodium malate respectively, crush and sieve, mix with adrenocorticotropic hormone, and put them into enteric-coated capsules to get it.
- Adrenocorticotropic hormone 4g sodium lauryl sulfate 40g, acylated chitosan 13g, sodium malate 130g.
- Preparation method take sodium lauryl sulfate, acylated chitosan and sodium malate respectively, crush and sieve, mix them with adrenocorticotropic hormone evenly, and put them into enteric-coated capsules.
- Adrenocorticotropic hormone 0.5g, sodium lauryl sulfate 40g, chitosan 13g, sodium citrate 130g.
- Preparation method take sodium lauryl sulfate, chitosan and sodium citrate respectively, crush and sieve, mix them with adrenocorticotropic hormone evenly, and put them into enteric-coated capsules.
- Adrenocorticotropic hormone 1g sodium lauryl sulfate 40g, chitosan 13g, sodium citrate 130g.
- Preparation method take sodium lauryl sulfate, chitosan and sodium citrate respectively, crush and sieve, mix them with adrenocorticotropic hormone evenly, and put them into enteric-coated capsules.
- Adrenocorticotropic hormone 3g sodium lauryl sulfate 40g, chitosan 13g, sodium citrate 130g.
- Preparation method take sodium lauryl sulfate, chitosan and sodium citrate respectively, crush and sieve, mix them with adrenocorticotropic hormone evenly, and put them into enteric-coated capsules.
- the examples include, but are not limited to, the above-mentioned preparation examples.
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Abstract
Description
Claims (12)
- 含有促肾上腺皮质激素或其衍生物的口服药物在制备治疗关节炎药物中的应用。
- 根据权利要求1所述的应用,其中所述的关节炎包括高尿酸引起的痛风。
- 根据权利要求1所述的应用,其中所述的口服药物制剂中的辅料为:表面活性剂、丙烯酸类聚合物、甲壳素或其衍生物、金属离子螯合剂。
- 根据权利要求1所述的应用,其中所述的口服药物制剂中的辅料为:表面活性剂、甲壳素或其衍生物、金属离子螯合剂。
- 根据权利要求3或4所述的应用,其中所述的表面活性剂包括阴离子表面活性剂或非离子表面活性剂中一种或几种。
- 根据权利要求3所述的应用,其中所述的丙烯酸类聚合物包括卡波姆、卡波姆910、卡波姆934、卡波姆934P中一种或几种。
- 根据权利要求3或4所述的应用,其中所述的甲壳素或其衍生物包括甲壳素、壳聚糖、羧甲基壳聚糖、酰化壳聚糖、烷基化壳聚糖、羟基化壳聚糖、壳聚糖季铵盐、壳聚寡糖、壳聚糖硫酸酯中的一种或几种。
- 根据权利要求3或4所述的应用,其中所述的金属离子螯合剂包括枸橼酸或其盐、酒石酸或其盐、苹果酸或其盐、马来酸或其盐、葡萄糖酸或其盐、乙二胺四乙酸或其盐、氨基三乙酸或其盐、二亚乙基三胺五乙酸或其盐中的一种或几种。
- 根据权利要求3所述的应用,其中表面活性剂、丙烯酸类聚合物、甲壳素或其衍生物与金属离子螯合剂的重量比为19-21:6-7:6-7:60-70。
- 根据权利要求4所述的应用,其中表面活性剂、甲壳素或其衍生物与金属离子螯合剂的重量比为19-21:6-7:60-70。
- 根据权利要求1所述的应用,其中所述的促肾上腺皮质激素口服药物制剂中溶液制剂配方中浓度为0.05mg/ml及更高浓度,在胶囊制剂中含量为0.4mg及更高含量。
- 根据权利要求1所述的应用,其中所述的促肾上腺皮质激素或其衍生物包括ACTH(1-39)、ACTH(1-24)和ACTH(1-17)。
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Citations (4)
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GB1064263A (en) * | 1963-06-28 | 1967-04-05 | Sandoz Ltd | Improvements in or relating to a pentacosapeptide |
US20180169191A1 (en) * | 2016-12-19 | 2018-06-21 | Eton Pharmaceuticals, Inc. | Adrenocorticotropic hormone-based pharmaceutical formulations and methods for fabricating and using thereof |
US20190134163A1 (en) * | 2016-12-19 | 2019-05-09 | Eton Pharmaceuticals, Inc. | Adrenocorticotropic hormone-based pharmaceutical formulations and methods for fabricating and using thereof |
CN112057629A (zh) * | 2019-06-10 | 2020-12-11 | 苏州兰鼎生物制药有限公司 | 一种药物组合物 |
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GB1369622A (en) * | 1970-12-26 | 1974-10-09 | Shionogi & Co | Pharmaceutical preparations of corticotropin -acitve poly-peptides and production thereof |
AU8131694A (en) * | 1993-11-02 | 1995-05-23 | Neurobiological Technologies, Inc. | Treatment for rheumatoid arthritis |
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2021
- 2021-03-31 CN CN202110345922.6A patent/CN115137809A/zh active Pending
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2022
- 2022-03-29 EP EP22778898.1A patent/EP4292605A1/en active Pending
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GB1064263A (en) * | 1963-06-28 | 1967-04-05 | Sandoz Ltd | Improvements in or relating to a pentacosapeptide |
US20180169191A1 (en) * | 2016-12-19 | 2018-06-21 | Eton Pharmaceuticals, Inc. | Adrenocorticotropic hormone-based pharmaceutical formulations and methods for fabricating and using thereof |
US20190134163A1 (en) * | 2016-12-19 | 2019-05-09 | Eton Pharmaceuticals, Inc. | Adrenocorticotropic hormone-based pharmaceutical formulations and methods for fabricating and using thereof |
CN112057629A (zh) * | 2019-06-10 | 2020-12-11 | 苏州兰鼎生物制药有限公司 | 一种药物组合物 |
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"Design and Development of Sustained-release and Controlled-release Formulations", 30 June 2006, BEIJING: CHINA MEDICAL SCIENCE AND TECHNOLOGY PRESS, CN, ISBN: 7506733609, article YAN, YAODONG EDITOR-IN-CHIEF: "Passage; Design and Development of Sustained-release and Controlled-release Formulations", pages: 153 - 154, XP009541552 * |
KHANNA PUJA P.; GLADUE HEATHER S.; SINGH MANJIT K.; FITZGERALD JOHN D.; BAE SANGMEE; PRAKASH SHRADDHA; KALDAS MARIAN; GOGIA MANEES: "Treatment of acute gout: A systematic review", SEMINARS IN ARTHRITIS AND RHEUMATISM., ELSEVIER, AMSTERDAM, NL, vol. 44, no. 1, 13 February 2014 (2014-02-13), AMSTERDAM, NL , pages 31 - 38, XP029012861, ISSN: 0049-0172, DOI: 10.1016/j.semarthrit.2014.02.003 * |
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