JP2023018932A - Injectable pharmaceutical composition applied to dialysis patient - Google Patents

Abstract

To provide an injectable pharmaceutical composition containing difelikefalin which can reduce human errors associated with dose preparation in a medical setting and reduce required manpower.SOLUTION: An injectable pharmaceutical composition for treating pruritus in a dialysis patient contains difelikefalin or a pharmacologically acceptable salt thereof. The injectable pharmaceutical composition is for reducing human errors associated with dose preparation in a medical setting and reducing required manpower. The injectable pharmaceutical composition contains difelikefalin or a pharmacologically acceptable salt thereof in an amount of 17.5 μg, 25.0 μg, 35.0 μg or 42.5 μg in terms of free difelikefalin, and is correspondingly to be administered to a dialysis patient whose dry body weight is less than 45 kg, is greater than or equal to 45 kg and less than 65 kg, is greater than or equal to 65 kg and less than 85 kg, or is greater than or equal to 85 kg, respectively.SELECTED DRAWING: Figure 1

Description

The present invention relates to a medicament, especially a pharmaceutical composition for dialysis patients containing diferikephalin or a pharmacologically acceptable salt thereof.

The cause of pruritus in dialysis patients has not been fully elucidated and is considered intractable. Multiple factors are involved in the development of pruritus, including dry skin, accumulation of endogenous substances, and overproduction of chemical mediators such as histamine and substance P. In addition, changes in immune function and disruption of opioid balance are also factors. In pruritic dialysis patients, the μ-opioid system, which induces itching, is superior to the κ-opioid system, which suppresses itching. It is considered.

Treatment of pruritus in dialysis patients includes topical treatment with moisturizing agents such as milky lotions and creams or steroids, topical or oral treatment with antihistamines and antiallergic drugs, and phototherapy using broad-wavelength ultraviolet rays.

In Japan, nalfurafine hydrochloride, an oral κ opioid receptor (KOR) agonist, is used for patients for whom existing treatments such as topical and oral treatments are inadequate.

Differikephalin is a novel peptidic KOR agonist that is being developed as an pruritus-ameliorating drug overseas (Non-Patent Document 1). It is also being developed in Japan. The peptide structure of diferikephalin is significantly different from that of previously developed low-molecular-weight heterocyclic KOR agonists that act on the central nervous system (CNS). migration is limited. Therefore, it has high selectivity for κ opioid receptors and weak action on other opioid receptors, so it does not easily migrate to the CNS and is expected to be marketed early as a drug with excellent safety and tolerability. there is

Patent No. 5807140 Patent No. 5244810

Steven Fishbane et al., Kidney International Reports, 2020, Vol. 5, p.600-610.

An object of the present invention is to provide an injectable pharmaceutical composition containing diferikephalin, which can reduce human error associated with dose preparation in medical practice and reduce labor.

Diferikephalin injection is an injection administered through the dialysis circuit at the time of blood return at the end of dialysis. However, currently, in foreign countries where clinical development is ahead, the dosage of diferikephalin injection is to be strictly adjusted in units of 1 kg according to the body weight of each individual patient in the medical field (non Patent document 1). Therefore, mistakes (incidents) are unavoidable as human beings in some process of dose preparation (for example, dose calculation itself based on free body equivalent concentration, body weight, dilution rate, and actual weighing, etc., depending on the case). There is a risk that Also, even if such mistakes can be sufficiently prevented by a double and triple check system, it would be very laborious, costly and difficult to adjust the dose every time in the medical field. As a result, administration for contributing to the treatment of patients may be avoided.

Therefore, in the medical field, it is unnecessary to strictly adjust the dosage in units of 1 kg for each patient's weight, reducing human error and labor associated with dosage adjustment in the medical field. It would be very beneficial if a new pharmaceutical formulation that could

However, there are various problems to be overcome in order to provide diferikephalin pharmaceutical preparations suitable for clinical practice. First, the number of pharmaceutical preparations provided to the medical site (standard number) must be acceptable in the medical site. In addition, there is no knowledge about the possibility of a new pharmaceutical formulation that does not strictly adjust the dosage in units of 1 kg for each patient's body weight, and it is difficult to predict efficacy and safety. Therefore, it was unclear whether such novel pharmaceutical formulations could even be provided. In other words, it is required that new pharmaceutical formulations have efficacy and safety for pruritus in dialysis patients, and that the effects on efficacy and safety between standards do not differ greatly depending on the dosage and administration. .

The present inventors first conceived that if the number of specifications for injection preparations of diferikephalin could be set to about 3 to 4 specifications, it would be particularly suitable for practical application in Japan. Based on analysis of the results of careful interviews with medical institutions in Japan with the formulation in mind, it was found that in the dialysis field, it is desirable to use single-use pharmaceutical formulations with a maximum of 3 to 4 specifications. Therefore, as a result of intensive examination of pharmaceutical formulations that can achieve the standard number, surprisingly, it was found that a combination of a specific dry weight category and a prescribed amount of diferikephalin was effective against pruritus in dialysis patients. , have efficacy and safety, and that no significant difference in efficacy and safety is observed between the dry weight classes, thereby completing the present invention.

In order to solve the above problems, the present invention has the following configuration as one aspect.

That is, an injectable pharmaceutical composition containing diferikephalin or a pharmacologically acceptable salt thereof for treating pruritus in dialysis patients,
The injectable pharmaceutical composition is an injectable pharmaceutical composition for reducing human error and labor associated with dose preparation in medical practice,
The pharmaceutical composition for injection contains 17.5 μg, 25.0 μg, 35.0 μg or 42.5 μg of diferikephalin or a pharmacologically acceptable salt thereof in terms of the free form of diferikephalin. Correspondingly, an injectable pharmaceutical composition for administration to a dialysis patient with a dry weight of less than 45 kg, 45 kg or more and less than 65 kg, 65 kg or more and less than 85 kg, or 85 kg or more,
The pharmaceutical composition for injection is enclosed in a pre-filled syringe in a unit dose for one-time use.
Injectable pharmaceutical composition.

The present invention provides an injectable pharmaceutical composition for reducing human error and labor associated with dose preparation in medical settings.

FIG. 3 shows the amount of change in NRS score (NRS Score) of hemodialysis patients. The vertical axis represents the amount of change in NRS score (Adjusted Mean±SE) in group A (A), group B (B), group C (C), and placebo group (Placebo) at 8 weeks of the treatment period. Shows the amount of change in NRS score (NRS Score) for each dry weight category. The vertical axis indicates the amount of change (Mean±SD) in the NRS score of group B (B) for each dry weight (DW) division at the 4th week of the treatment period. Shows the amount of change in NRS score (NRS Score) for each dry weight category. The vertical axis indicates the amount of change (Mean±SD) in the NRS score of group C (C) for each dry weight (DW) division at the 4th week of the treatment period.

Hereinafter, embodiments of the present invention will be described in more detail.

In the present invention, each term has the following meaning unless otherwise specified.

Difelikefalin (INN) is a compound represented by the following formula.

In the present invention, diferikephalin can be converted into a pharmacologically acceptable salt thereof according to a conventional method, if necessary. Such diferikephalin salts include, for example, salts derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid, acetic acid, propionic acid, succinic acid and glycolic acid. , stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, pamoic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, sulfanilic acid, 2-acetoxybenzoic acid, fumaric acid, toluene Included are salts derived from organic acids such as sulfonic acid, methanesulfonic acid, ethanedisulfonic acid, oxalic acid, isethionic acid, and the like. Diferikephalin acetate (JAN) is preferred.

In the present invention, "pharmacologically acceptable salt of diferikephalin" also includes solvates with pharmaceutically acceptable solvents such as water and ethanol.

The diferikephalin of the present invention can be produced by a known method. For example, they can be produced by the methods described in Patent Documents 1 and 2 or methods based thereon.

One aspect of the injectable pharmaceutical composition of the present invention is an injectable, preferably a single-use type that can reduce human error and labor associated with dose preparation in medical practice at the time of administration. is an injection of Such injections include, for example, injections in which all of the pre-filled drug solution is used up, and injections in which the drug solution is completely used up after all of the filled drug solution has been sucked up with a syringe. Forms of injections that can be used in this way include, for example, prefilled syringe formulations, vial formulations, and ampoule formulations.

The pharmaceutical composition for injection of the present invention can be provided as injections of multiple standards with different concentrations of diferikephalin, with the amount of drug solution filled in a vial or prefilled syringe being constant. Moreover, as one embodiment, the concentration of diferikephalin is kept constant, and it can be provided as an injection of multiple standards with different amounts of drug solution. The amount of drug solution to be filled is not particularly limited as long as it can be filled into an injection, but is preferably in the range of 0.3 mL to 2.5 mL. The amount of diferikephalin to be encapsulated is 17.5 μg, 25.0 μg, 35.0 μg or 42.5 μg in terms of free form, corresponding to less than 45 kg, 45 kg to less than 65 kg, 65 kg to less than 85 kg, or 85 kg or more. is intended to be administered to dialysis patients of dry weight weight of

The injectable pharmaceutical composition of the present invention is prepared using diferikephalin or a pharmaceutically acceptable salt thereof as an active ingredient and at least one pharmaceutically acceptable carrier. The injectable pharmaceutical composition of the present invention can also be prepared by appropriately mixing, diluting or dissolving with a pharmaceutically acceptable carrier by a method known in pharmaceutical science. Such pharmaceutically acceptable carriers include, for example, tonicity agents, sodium chloride, potassium chloride, glycerin, mannitol, sorbitol, boric acid, borax, glucose, propylene glycol and the like. Sodium chloride and potassium chloride are preferred. Buffers can include acetic acid, tartaric acid, lactic acid, citric acid, boric acid, phosphoric acid, carbonic acid and salts thereof. More specific examples include acetic acid and sodium acetate, citric acid and trisodium citrate, sodium hydrogen carbonate and sodium carbonate, sodium dihydrogen phosphate and disodium hydrogen phosphate, and the like. Preferred are acetic acid and sodium acetate, sodium hydrogen carbonate and sodium carbonate. Preservatives include paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, benzalkonium chloride, sodium dehydroacetate, sodium edetate, boric acid, borax and the like. Preferable examples include paraoxybenzoic acid esters and benzalkonium chloride. Thickeners include hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyethylene glycol and the like. Hydroxyethyl cellulose and hydroxypropyl cellulose are preferred. Stabilizers include sodium bisulfite, sodium thiosulfate, sodium edetate, sodium citrate, ascorbic acid, dibutylhydroxytoluene and the like. Sodium citrate and ascorbic acid are preferred. Examples of pH adjusters include hydrochloric acid, sodium hydroxide, phosphoric acid and acetic acid. Hydrochloric acid and sodium hydroxide are preferred.

The solvent used in the pharmaceutical composition for injection of the present invention is not particularly limited as long as it can be used for injections, and is preferably an aqueous solvent, such as water for injection or physiological saline.

Although the pH of the injectable pharmaceutical composition of the present invention is not particularly limited, for example, the pH is preferably 5.0 or less, more preferably in the range of 4.0 to 5.0.

The pharmaceutical composition for injection of the present invention is usually provided as an injection having multiple specifications with different contents of diferikephalin. As one aspect of the present invention, a prescribed amount of diferikephalin is provided to a medical institution as an injection having a plurality of content standards, which is pre-filled according to the patient's dry weight category. The content standard number (standard number) is not particularly limited as long as it is a standard number acceptable in medical practice, but is preferably 4 or less, more preferably 3 or less. The number of specifications is usually the same as the number of dry weight categories for a patient. It can also be provided as a standard number of injections that is less than the number of .

The term “dry weight” refers to the target body weight after dehydration that is set as an index for treatment plans according to the condition of each individual patient in hemodialysis treatment. , the body weight that does not cause an excessive drop in blood pressure during dialysis and that has a low burden on the cardiovascular system in the long term. That is, body weight without excessive fluid retention. Dry weight is usually determined by a physician and is set, for example, to approximate as closely as possible the post-void weight of a patient with normal renal function. Therefore, dry weight may also mean the lowest body weight that can be safely reached after hemodialysis without exhibiting symptoms of hypotension associated with excessive dehydration such as cramps.

The dry weight can be set according to generally adopted setting indices. Indicators include, for example, no significant drop in blood pressure during dialysis, blood pressure at the end of dialysis not higher than blood pressure at the start of dialysis, no peripheral edema, no pleural effusion or pulmonary congestion on chest X-ray, cardiothoracic A ratio of 50% or less (53% or less for women) is used.

The injectable pharmaceutical composition of the present invention is used to administer a defined amount of diferikephalin based on the patient's dry weight category. This makes it possible to avoid the complicated administration method of adjusting the dosage in units of 1 kg of body weight each time the drug is administered, and to reduce human error and labor associated with dosage adjustment in the medical field. In the present invention, the prescribed amount of diferikephalin based on the patient's dry weight category is, for example, 17.5 μg for adults with a dry weight of less than 45 kg, and 25.0 μg for patients with a dry weight of 45 kg or more and less than 65 kg. μg, 35.0 μg for patients with dry weights greater than or equal to 65 kg and less than 85 kg, and 42.5 μg for patients with dry weights greater than or equal to 85 kg.

In another embodiment, the patient with a dry weight of 85 kg or more may be a patient with a dry weight of 85 kg or more and less than 100 kg, a dry weight of 85 kg or more and less than 105 kg, a dry weight of 85 kg or more and less than 110 kg, or a dry weight of 85 kg or more and less than 115 kg.

When the pharmaceutical composition for injection of the present invention is applied to dialysis patients, for example, the pharmaceutical composition can be used by injecting it into the dialysis circuit vein side at the time of blood return at the end of dialysis three times a week. If administration through the dialysis circuit is not possible due to trouble with the dialysis circuit, etc., administration by intravenous injection can also be used. For occasional 4-week dialysis, 4-week dosing can also be used.

The injectable pharmaceutical composition of the present invention is useful for treating pruritus. In the present invention, pruritus is not limited as long as it is a disease that accompanies itching. Since the injectable pharmaceutical composition of the present invention is a KOR agonist, it is also used for the treatment of mood swings, improvement of depressive symptoms, postoperative pain, osteoarthritis, and sleep disorders associated with dialysis. be able to.

In the present invention, the therapeutic effect of pruritus can also be evaluated using an evaluation method known to those skilled in the art that scores the degree of itching felt by a subject. Examples include Numerical Rating Scale (NRS), Visual Analogue Scale (VAS), Shiratori severity criteria, Skinindex-10, Skinindex-16, 5-D Itch Scale, and Patient Global Impression of Change (PGIC).

The NRS, which can be said to be the most representative index, is an integer from 0 to 10, with 0 representing "no itch" and 10 representing "maximum possible itch" for the most intense itching felt during the day. Evaluate with In general, an NRS of 1 or more and less than 4 is rated as mild, 4 or more and less than 7 is moderate, and 7 or more is rated as severe. On the VAS, the left end of the 100 mm line was designated as “no itch” and the right end was designated as “maximum possible itch”. Measure and evaluate the length. There is a correlation between the evaluation of NRS and VAS, but NRS is a simpler evaluation method. The NRS score for pruritus is widely used in clinical trials as a measure of pruritus.

The severity scale of Shiratori is based on scores from 0 to 4 ranging from "no symptoms" to "severe itching", and each symptom during the day and at night is judged and evaluated by the subject himself/herself. Shiratori's severity criteria are widely used in evaluating the degree of itching in the domestic dermatology field, and the impact on daily life is used as the criteria for determining severity.

The Skindex-16 rates "never bothered" to "always bothered" as scores from 0 to 6, respectively. Skindex-16 has been applied to QOL evaluation related to skin diseases.

The 5-D Itch Scale measures five components of itch: duration, extent, tendency, adverse effects, and distribution.

The PGIC rated global symptoms of itch as "much better", "better", "slightly better", "no change", "slightly worse", "worse" and " It has become very bad."

The effectiveness of the drug against itching can also be confirmed by evaluating the amount of change in the score in the evaluation method described above. Specifically, the degree of itching before drug administration (baseline) is compared with the degree of itching after drug administration, and if the degree of itching improves, it is evaluated as being attenuated. You can also In the present invention, from the viewpoint of improving the patient's QOL, the efficacy against itching is evaluated in addition to the improvement of the NRS or VAS score, as well as the QOL score (Shiratori severity criteria, Skinindex-16, 5-D Itch Scale, PGIC ) is also preferably observed.

In the present invention, it is preferred that no significant difference in the efficacy and safety of the injectable pharmaceutical composition of the present invention is observed between the dry weight classes. Specifically, whether any improvement in pruritus is observed in any dry weight category, pre-dialysis trough value (plasma drug concentration immediately before administration (plasma diferikephalin (unchanged drug) concentration)) It is preferred that no large fluctuations are observed in or both are satisfied. The plasma concentration of diferikephalin can be measured by a general method, for example, by an LC-MS/MS method.

One embodiment of the injectable pharmaceutical composition of the present invention includes a kit comprising (a) the injectable pharmaceutical composition of the present invention; and (b) one or more labels or package inserts attached to or attached to a container. be done. In the present invention, "including an attached document" includes not only the case where an instruction manual is enclosed, but also the case where a means for making available the information describing the contents of the attached document is specified. The case where the means to make the information containing the content of the package insert available is specified, as long as it is a means by which the content can be confirmed, but the information can be used, for example, through electronic communication lines There is a means to Specifically, there is a case where a QR code (registered trademark) or a URL is written on a commercially available pharmaceutical preparation.

EXAMPLES The present invention will be described in more detail below based on examples, but the present invention is not limited to the contents thereof. In the examples, the description of the amount of diferikephalin means the amount of free form (free form conversion value) administered as diferikephalin acetate.
Example 1
Clinical trial in hemodialysis patients with pruritus (double-blind, parallel-group comparative study)
1. Study method (1) Administration method Subjected to 247 patients, group A (61 cases), group B (61 cases), group C (62 cases) and placebo group (63 cases), each investigational drug 3 times a week For 8 weeks, the drug was injected into the venous side of the dialysis circuit at the time of blood return at the end of dialysis. The study period was in the order of a pre-observation period (2 weeks before the transition to the treatment period), a treatment period (8 weeks), and a follow-up period (2 weeks after the end of the treatment period). was not administered.
(2) Investigational drug
Group A: Injection of 0.025 mg/mL diferikephalin dissolved in 0.04 M isotonic buffered acetic acid solution (pH 4.5)
Group B: Injection of 0.05 mg/mL diferikephalin dissolved in 0.04 M isotonic buffered acetic acid solution (pH 4.5)
Group C: 0.04 M isotonic buffered acetic acid solution (pH 4.5) containing 0.1 mg/mL injection of diferikephalin Placebo group: 0.04 M isotonic buffered acetic acid solution (pH 4.5)
(3) Dosage The dose of the investigational drug and the dose of diferikephalin in each administration group was determined according to the dry weight category of each patient on the day of administration according to the table below.

2. Efficacy and safety evaluation items Efficacy was evaluated based on the following subjective symptoms related to itching. In each of the following scores, the 0th week of the treatment period was taken as the baseline, and the difference from the baseline was taken as the amount of change.
(1) NRS score
The strongest itching felt during the day was evaluated as an integer from 0 to 10, with 0 being "no itch" and 10 being "maximum possible itch".
(2) Itching score based on Shiratori severity criteria
Once a day, the degree of itching from the time of waking up on the day before evaluation to the time of waking up on the day (including during sleep) was scored on a scale of 0 to 4, from "no symptoms" to "severe itching". Each symptom during the day and night was evaluated.
(3) Skinindex-16 score At the first week's visit (before administration of the study drug), the frequency of suffering from itching over the past week was determined. A score of 0 to 6 was assigned, ranging from "not bothered at all" to "always bothered".
(4) 5-D Itch Scale score At the beginning of the week (before administration of the study drug), review the itch status for the past 2 weeks and determine the 5 components of itch (duration, degree, tendency, adverse effects, distribution) bottom.
(5) At the first visit of the PGIC score week, the general symptoms of itching compared with the previous observation period were "very much improved", "improved", "slightly improved", "no change", " It was evaluated on a 7-point scale of "slightly worsened", "worse" and "very worsened".

As an analysis method, a mixed effects model for repeated measures (MMRM) was used for the average NRS score and the itch score based on the Shiratori severity criteria. Specifically, for the mean NRS score, the amount of change in the score was the objective variable, the group, the observation time point, and the interaction between the group and the observation time point were the fixed effects, the mean baseline score, the use of pretreatment drugs for itching, and the Analysis was performed using the presence or absence of specific signs or symptoms to be confirmed in the pre-observation period as a covariate and the subject as a random effect. In the itch score based on the Shiratori severity criteria, the change in score was the objective variable, the group, observation time point, and interaction between group and observation time were fixed effects, the baseline mean score was a covariate, and the subject was a random effect. was analyzed as

For safety, the number of occurrences of adverse events and adverse drug reactions, the number of occurrences, the incidence rate, etc. were evaluated.
3. Results (1) Fig. 1 shows the amount of change in the NRS score at the 8th week of the treatment period.

The amount of change in the NRS score at week 8 of the treatment period was -2.86 in the placebo group, -2.97 in group A, -3.65 in group B and -3.64 in group C, and groups B and C compared to the placebo group. showed significant improvement (MMRM, P<0.05).
(2) Figures 2 and 3 show the amount of change in the NRS score for each dry weight category in groups B and C during the 4-week treatment period when efficacy was maximized. As shown in Figures 2 and 3, in groups B and C, an improvement in the NRS score was confirmed in both dry weight categories.
(3) The amount of change in the itch score based on the severity criteria for Shiratori at week 8 of the treatment period (the amount of change in either daytime or nighttime, whichever score is greater) was -1.00 in the placebo group, group A - 1.14, Group B -1.31 and Group C -1.31, showing significant improvement in Groups B and C compared to placebo (MMRM, P<0.05).
(4) The amount of change in the overall Skinindex-16 score at week 8 of the treatment period was -24.25 in the A group, -27.79 in the B group and -22.69 in the C group, compared to -24.04 in the placebo group. was taken.
(5) The amount of change in the 5-D Itch Scale total score at 8 weeks of the treatment period was -5.8 in the placebo group, -6.6 in group A, -6.5 in group B and -6.8 in group C, and the dose of group A or higher A trend toward improvement was observed in
(6) The proportion of subjects whose PGIC score at the final evaluation of the treatment period was “improved” and “improved” was 24.2% and 17.7% in the placebo group, 34.4% and 19.7% in group A, and 34.4% and 19.7% in group B. 28.8 and 37.3%, and 38.3 and 31.7% in group C, showing significant improvement over placebo in groups B and C (two-sample Wilcoxon test, P<0.01).
(7) The incidence of adverse events during the treatment period increased dose-dependently to 66.7% in the placebo group, 72.1% in the A group, 77.0% in the B group, and 85.5% in the C group. and significantly higher (Fisher's exact test, P<0.05).

The incidence of side effects during the treatment period was 11.1% in the placebo group, 14.8% in the A group, 14.8% in the B group, and 27.4% in the C group, with a dose-dependent increase. high (Fisher's exact test, P<0.05).

From the above results, in groups B and C, a significant improvement effect on pruritus in hemodialysis patients was shown. On the other hand, in group A, no significant improvement effect was shown. In addition, the incidence of adverse events and side effects during the treatment period in Group B showed no significant difference from the placebo group, confirming that Group B is a dose with excellent safety and tolerability. .
4. Endpoints related to pharmacokinetics (1) Measurement method: In Groups B and C, "drug concentration in plasma: concentration of diferikephalin (unchanged form) in plasma" was measured by LC-MS/MS method.
(2) Results: Group B (less than 45 kg (4 cases), 45 kg or more and less than 65 kg (32 cases), 65 kg or more and less than 85 kg (15 cases), 85 kg or more (1 case)) at 7 weeks in the dry weight category The geometric mean values of pre-dialysis trough values (pre-dialysis plasma diferikephalin concentrations) were 0.5903 ng/mL, 0.5826 ng/mL, 0.5275 ng/mL and 0.7480 ng/mL, respectively. Group C (less than 45 kg (3 cases), 45-65 kg (32 cases), 65-85 kg (15 cases), 85 kg or more (2 cases)) pre-dialysis trough value at week 7 ( The geometric mean values of diferikephalin concentration in plasma before dialysis) were 0.9306 ng/mL, 0.9700 ng/mL, 1.0671 ng/mL and 1.0396 ng/mL, respectively.

Based on the above results, there was no significant difference in the fluctuation range of plasma diferikephalin concentration between the dry weight categories in Group B. Similar results were obtained in group C as well.

From the results of the Examples, Group B showed efficacy and safety against pruritus in hemodialysis patients of various body weights without the need to adjust the dosage in units of 1 kg of body weight of individual patients. rice field.
Therefore, it was shown that the pharmaceutical composition for injection of the present invention can reduce human error and labor associated with dose preparation in medical practice.

The injectable pharmaceutical composition of the present invention is extremely useful as a medicine applied to dialysis patients.

Claims (1)

An injectable pharmaceutical composition containing diferikephalin or a pharmacologically acceptable salt thereof for treating pruritus in dialysis patients,
The injectable pharmaceutical composition is an injectable pharmaceutical composition for reducing human error and labor associated with dose preparation in medical practice,
The pharmaceutical composition for injection contains 17.5 μg, 25.0 μg, 35.0 μg or 42.5 μg of diferikephalin or a pharmacologically acceptable salt thereof in terms of the free form of diferikephalin. Correspondingly, an injectable pharmaceutical composition for administration to a dialysis patient with a dry weight of less than 45 kg, 45 kg or more and less than 65 kg, 65 kg or more and less than 85 kg, or 85 kg or more,
The pharmaceutical composition for injection is enclosed in a pre-filled syringe in a unit dose for one-time use.
Injectable pharmaceutical composition.

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